5 Minute Anesthesia Consult (2013).pdf

The 5-Minute Anesthesia Consult

CHIEF EDITORIAL ASSISTANT Matthew C. Gertsch, MD Resident Physician Department of Anesthesia, Critical Care and Pain Medicine Harvard Medical School Massachusetts General Hospital Boston, Massachusetts EDITORIAL ASSISTANTS J. Scott Bluth Medical Student University of Texas Medical School at Houston Houston, Texas Mark R. Bombulie Medical Student University of Texas Medical School at Houston Houston, Texas Kelly A. Bruno Medical Student The University of North Carolina, School of Medicine Chapel Hill, North Carolina N. Matthew Decker, BS Medical Student Loyola University Chicago Stritch School of Medicine Maywood, Illinois David Frey, DO Resident Physician Department of Anesthesiology and Pain Medicine University of Washington Medical School University of Washington Medical Center Seattle, Washington Megan Dale Henley Medical Student The University of North Carolina, School of Medicine Chapel Hill, North Carolina Thomas J. Hopkins, MD, MMCi Resident Physician

Department of Anesthesiology Duke University School of Medicine Duke University Medical Center Durham, North Carolina Rachel M. Little, MPH Medical Student The University of North Carolina, School of Medicine Chapel Hill, North Carolina Carolyn Mohr, MD Resident Physician Department of Anesthesiology University of Colorado School of Medicine Anschutz Medical Campus Denver, Colorado Olutoyosi Ogunkua, MD Resident Physician Department of Anesthesiology and Pain Management University of Texas Southwestern School of Medicine University of Texas Southwestern Medical Center at Dallas Dallas, Texas Michael J. Oleyar, DO Resident Physician Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Blake W. Perkins Medical Student University of Illinois College of Medicine Peoria, Illinois Matthew M. Peterson Medical Student Tulane University School of Medicine New Orleans, Louisiana Lauren Mai Pieczynski, MD Resident Physician Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania

Philadelphia, Pennsylvaniaz Adam M. Stuart Medical Student Virginia Commonwealth University School of Medicine Richmond, Virginia Lindsay Veit, MD Resident Physician Department of Anesthesiology Rush Medical College Rush University Medical Center Chicago, Illinois CONSULTANT EDITOR Anita Gupta

The 5-Minute Anesthesia Consult Editor Nina Singh-Radcliff, MD

Section Editor Alan J. Kover, MD, PharmD Clinical Assistant Professor Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Associate Editors Kris E. Radcliff, MD Assistant Professor of Orthopedic Surgery and Neurological Surgery Thomas Jefferson University The Rothman Institute Philadelphia, Pennsylvania Emily J. Baird, MD, PhD Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Julie Scott Taylor, MD, MSc Clinical Assistant Professor Department of Anesthesiology Stanford University Palo Alto, California

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Printed in China (or US)? Library of Congress Cataloging-in-Publication Data Singh-Radcliff, Nina.

The 5-minute anesthesia consult / [edited by] Nina Singh-Radcliff. p.; cm. - (5-minute consult)

Includes bibliographical references and index. ISBN 978-1-4511-1894-0 (alk. paper) I. Title. II. Series: 5-minute consult.

[DNLM: 1. Anesthesia-Handbooks. 2. Perioperative Period-Handbooks. 3. Surgical Procedures, Operative-Handbooks. WO 231]

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10 9 8 7 6 5 4 3 2 1

To my parents, Dilip and Madhulika Singh, for their unconditional love and support throughout my life and career and

teaching me by example about kindness, honesty, and dedication. Children cannot choose their parents, but if I had been

given the opportunity, I would choose them. I also need to give a special thanks to Carmen, my first child, who helped me edit the book while in utero. And finally to my husband, Dr. Kris Radcliff, who served as an Associate Editor to this book.

Words cannot convey my gratitude for his contribution to, and support, with this text. I have known Kris for almost one-third of my life and he remains the most intelligent, kind, patient, humble, and wonderful person I know. He still makes my heart flutter when I see him. He is the best thing that has ever happened to me and I am truly blessed to be able to call him my husband and share my life with him.

CONTRIBUTORS Ali R. Abdullah, MBChB

Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Erik E. Abel, PharmD, BCPS Clinical Assistant Professor Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Benjamin Abraham, MD Department of Anesthesiology The Cleveland Clinic Cleveland, Ohio Andaleeb Abrar Ahmed, MBBS, MD, MPH Resident Physician Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Moustafa Ahmed, MD Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Interim Chief, Philadelphia VA Medical Center Philadelphia, Pennsylvania Jane C. Ahn, MD Assistant Professor Department of Anesthesiology and Perioperative Care

University of California, Irvine School of Medicine University of California, Irvine Douglas Hospital Irvine, California Arun Alagappan, MD

Resident Physician Department of Anesthesiology Mount Sinai School of Medicine St. Joseph’s Hospital and Regional Medical Center Paterson, New Jersey Brooke Albright, MD, MAJ, MC

Assistant Professor of Anesthesiology Critical Care Air Transport Team Physician United States Air Force Landstuhl, Germany Tayab R. Andrabi Associate Professor Department of Anesthesiology & Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Jonathan Anson, MD Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania John L. Ard Jr., MD Assistant Professor Department of Anesthesiology New York University School of Medicine NYU Langone Medical Center New York, New York Radha Arunkumar, MD Associate Clinical Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Alan Ashworth, MBChB, FRCA, FFICM

Consultant in Cardiothoracic Anaesthesia and Intensive Care University Hospital of South Manchester Manchester, UK Kalliopi Athanassiadi, MD, PhD

Senior Thoracic Surgeon Department of Surgery University of Athens Medical School Athens, Greece Joshua A. Atkins, MD, PhD

Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Ahmed Fikry Attaallah, MD, PhD Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia John G. T. Augoustides, MD, FASE, FAHA Associate Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Naola Austin, MD Resident Physician Department of Anesthesiology and Pain Medicine University of Washington Medical School University of Washington Medical Center Seattle, Washington Stephen O. Bader, MD

Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia

Sean M. Bagshaw, MD, MSc, FRCPC Assistant Professor Division of Critical Care University of Alberta Edmonton, AB Canada Timothy R. Ball, MD

Assistant Clinical Professor Department of Anesthesiology Texas A&M College of Medicine Scott & White Memorial Hospital Temple, Texas Andrew L. Barker, MD Resident Physician Department of Anesthesiology Texas A&M College of Medicine Scott and White Hospital Temple, Texas Viachaslau Barodka, MD Assistant Professor Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Amy Barulic, BS, MHS Research Assistant Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Colin Bauer, MD Chief Resident Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Shawn T. Beaman, MD Assistant Professor Associate Residency Program Director

Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania John F. Bebawy, MD Assistant Professor of Anesthesiology and Neurological Surgery Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois A. Katharina Beckmann, MD

Fellow, Cardiac Anesthesia Department of Anesthesiology Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois Sascha Beutler, MD, PhD Assistant Professor Assistant Program Director Department of Anesthesiology, Perioperative and Pain Medicine Harvard Medical School Brigham and Women’s Hospital Boston, Massachusetts Dmitri Bezinover, MD, PhD Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Amar M. Bhatt, MD Resident Physician Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Shreyas Bhavsar, DO Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center

Houston, Texas Jeanna Blitz, MD

Assistant Professor Department of Anesthesiology New York University School of Medicine NYU Langone Medical Center New York, New York J. Scott Bluth, BS Medical Student University of Texas Medical School at Houston Houston, Texas Michael L. Boisen, MD Fellow, Cardiothoracic Anesthesiology Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Eric Bolin, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Mark R. Bombulie, BS

Medical Student University of Texas School of Medicine at Houston Houston, Texas James D. Boone, MD Instructor Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois Mary Brady, MD, FASE Assistant Professor Medical Director, Post-Anesthesia Care Unit Director, Intraoperative Transesophageal Echocardiography Program Department of Anesthesiology and Critical Care Medicine

The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Michelle Braunfeld, MD

Clinical Professor Department of Anesthesiology and Critical Care Medicine David Geffen School of Medicine at UCLA Chief, Department of Anesthesiology Greater Los Angeles Veterans Affairs Hospital Los Angeles, California Tod A. Brown, MD

Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Charles H. Brown IV, MD Assistant Professor Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Kelly Bruno, BS, MD Medical Student University of North Carolina School of Medicine Chapel Hill, North Carolina Ethan O. Bryson, MD Associate Professor Department of Anesthesiology and Psychiatry Mount Sinai School of Medicine The Mount Sinai Hospital New York, New York Arne O. Budde, MD, DEAA

Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania

James Cain, MD

Department of Anesthesiology and Pediatrics University of Pittsburgh School of Medicine Children’s Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania James M. Callas, MD

Chief, Department of Radiology King’s Daughters Clinic Temple, Texas Neal Campbell, MD

Assistant Professor Department of Anesthesiology & Pediatrics University of Pittsburgh School of Medicine Children’s Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania Elena C. Capello, MD Universita di Torino Dipartimento di Discipline Medico-Chirurgiche Sezione di Anestesiologia e Rianimazione Ospedale S. Giovanni Battista John B. Carter, MD Associate Professor Department of Anesthesiology Oklahoma University College of Medicine Oklahoma University Health Sciences Center Oklahoma City, Oklahoma Michael Carter, MD, PhD Resident Physician Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Daniel Castillo, MD

Assistant Professor Department of Anesthesiology University of Florida College of Medicine Shands Jacksonville Medical Center Jacksonville, Florida

Davide Cattano, MD, PhD

Associate Professor Department of Anesthesiology University of Texas Medical School at Houston Memorial Hermann Hospital Houston, Texas Laura F. Cavallone, MD

Assistant Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri John T. Chalabi, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Vinay Chandrasekhara, MD Instructor Division of Gastroenterology, Department of Medicine Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Jean Charchaflieh, MD, DrPH, FCCM, FCCP Associate Professor Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Verghese T. Cherian, MBBS, MD, FFARCSI Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Jason Choi, MD Resident Physician

Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Christopher G. Choukalas, MD, MS Assistant Professor Department of Anesthesia and Perioperative Care University of California, San Francisco San Francisco VA Medical Center San Francisco, California Jason Han Chua, MD

Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Theodore J. Cios, MD, MPH Resident Physician Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Carlee Clark, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Matthew D. Cohen, DO Assistant Professor Chief, Division of Acute Pain and Regional Anesthesia Department of Anesthesiology University of Oklahoma The University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma Seth R. Cohen, DO Resident Physician Department of Anesthesiology

University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania John F. Coleman, MD

Clinical Fellow Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Lydia A. Conlay, MD, PhD

Russell D and Mary B Sheldon Professor Vice Chairwoman for Academic Affairs Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Craig R. Cook, MD, PhD Resident Physician Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Daniel Cormican, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Charles E. Cowles Jr., MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Ryan Crowley, MD Staff Physician Department of Anesthesiology Legacy Good Samaritan Hospital Portland, Oregon

William C. Culp Jr., MD, FASE

Associate Professor Department of Anesthesiology Texas A&M University College of Medicine Scott and White Hospital Temple, Texas Cristina Cunanan, MD

Resident Physician Department of Anesthesiology and Critical Care Medicine David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Priti G. Dalal, MD, FRCA Associate Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Patricia Dalby, MD Associate Professor Department of Anesthesiology University of Pittsburgh School of Medicine Magee-Women’s Hospital of UPMC Pittsburgh, Pennsylvania Lori Dangler, MD, MBA Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Nisha Dave, DO, PharmD Resident Physician Mount Sinai School of Medicine St. Joseph’s Regional Medical Center Paterson, New Jersey Alberto J. de Armendi, MD, AM, MBA Professor Chief, Pediatric Anesthesia Department of Anesthesiology

Oklahoma University College of Medicine Children’s Hospital of Oklahoma Oklahoma City, Oklahoma Stephen Dechter, DO N. Matthew Decker, BS Medical Student Loyola University Chicago Stritch School of Medicine Maywood, Illinois Matthew Delph, MD

Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Jagan Devarajan, MD, FRCA Associate Staff Department of Anesthesiology The Cleveland Clinic Cleveland, Ohio Anahat Dhillon, MD Assistant Clinical Professor Department of Anesthesiology and Critical Care Medicine David Geffen School of Medicine at UCLA Ronald Reagan Medial Center Los Angeles, California Bradley T. Dollar, MD Assistant Professor Residency Program Director Department of Radiology Texas A&M College of Medicine Scott and White Hospital Temple, Texas Kathleen S. Donahue, DO, FAAP Associate Professor Associate Vice Chair, OR Management Department of Anesthesiology Penn State College of Medicine

Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Shawna Dorman, MD

Instructor Department of Anesthesiology New York University School of Medicine NYU Langone Medical Center New York, New York Corey C. Downs, MD

Staff Anesthesiologist Surgical and Perioperative Careline VA Greater Los Angeles Healthcare System Los Angeles, California Emily L. Drennan, MD Assistant Professor Department of Anesthesiology University of Texas Medical School at Houston Memorial Hermann Hospital Houston, Texas Rebecca A. Drinkaus, MD Assistant Professor Department of Anesthesiology Oklahoma University College of Medicine Oklahoma University Health Sciences Center Oklahoma City, Oklahoma Peter Drocton, MD Department of Anesthesiology Cedars-Sinai Medical Center Los Angeles, California Department of Anesthesiology Olive View - UCLA Medical Center Sylmar, California Mirsad Dupanovic, MD

Assistant Professor Department of Anesthesiology Kansas University School of Medicine Kansas University Medical Center Kansas City, Kansas

Victor Duval, MD

Assistant Clinical Professor Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Ramana V. Duvvuri, MD

Assistant Clinical Professor Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California J. Andrew Dziewit, MD Attending Physician Department of Anesthesia Crozer Chester Medical Center Upland, Pennsylvania Jill Eckert, DO Assistant Professor Residency Program Director Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Nabil Elkassabany, MD Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Matthew Ellison, MD Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia Trent Emerick, MD Resident Physician

Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Thomas I. Epperson III, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Zhuang-Ting Fang, MD, MSPH

Associate Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Jared Feinman, MD Fellow, Cardiothoracic Anesthesia Department of Anesthesia, Critical Care and Pain Medicine Harvard Medical School Massachusetts General Hospital Boston, Massachusetts Larry C. Field, MD Assistant Professor Medical Director, Medical/Surgical ICU Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Robert S. Fitzgerald, LittB, STB, MA, STM, PhD Professor Environmental Health Sciences, Physiology, Medicine The Johns Hopkins University Baltimore, Maryland Linzy Fitzsimons, MD Resident Physician Department of Anesthesiology David Geffen School of Medicine at UCLA

Ronald Reagan Medical Center Los Angeles, California Melissa Flanigan, DO

Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia Andrew Fond, MD

Assistant Clinical Professor Department of Anesthesiology and Pain Management University of Southern California Los Angeles, California Siyavash Fooladian, MD, MPH Fellow, Cardiothoracic Anesthesiology Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Caroline Fosnot, DO, MS Clinical Instructor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania John J. Freely Jr., MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Megan M. Freestone-Bernd, MD Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania

Katy E. French-Bloom, MD

Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas John C. Frenzel, MD

Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas David Frey, BA

Medical Student Ohio University College of Osteopathic Medicine Athens, Ohio David P. Frey, DO Resident Physician Department of Anesthesiology and Pain Medicine University of Washington Medical School University of Washington Medical Center Seattle, Washington Elizabeth A.M. Frost, MD Professor of Anesthesiology Mount Sinai School of Medicine The Mount Sinai Hospital New York, New York Kamilia S. Funder, MD Physician Department of Anesthesia Copenhagen University Hospital, Rigshospitalet Copenhagen, Denmark Jorge A. Galvez, MD Fellow, Pediatric Anesthesiology Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Children’s Hospital of Philadelphia Philadelphia, Pennsylvania Wei Dong Gao, MD, PhD

Associate Professor Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Stephanie Gargani, MD

Resident Physician Department of Anesthesiology Mount Sinai School of Medicine St. Joseph’s Regional Medical Center Paterson, New Jersey Andrew Geller, MD Resident Physician Department of Anesthesiology Charles Drew University of Medicine and Science Cedars-Sinai Medical Center Los Angeles, California Matthew C. Gertsch, MD Resident Physician Department of Anesthesia, Critical Care and Pain Medicine Harvard Medical School Massachusetts General Hospital Boston, Massachusetts Ileana Gheorghiu, MD Assistant Professor Department of Anesthesiology University of Maryland School of Medicine University of Maryland Medical Center Baltimore, Maryland Brian Gierl, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Lori Gilbert, MD Assistant Clinical Professor Department of Anesthesiology and Critical Care

Perelman School of Medicine at the University of Pennsylvania Philadelphia VA Medical Center Philadelphia, Pennsylvania Ronnie J. Glavin, MB, ChB, MPhil, FRCA, FRCP (Glas) Consultant Anesthetist Victoria Infirmary Glasgow, United Kingdom

Christine E. Goepfert, MD, PhD, DESA Instructor and Visiting Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Emily Gordon, MD Instructor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Shannon M. Gossett-Popovich, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Amitabh Goswami, DO, MPH Fellow, Pain Management Department of Anesthesiology and Pain Medicine University of California, Davis School of Medicine UC Davis Medical Center Sacramento, California Ori Gottlieb, MD Assistant Professor Department of Anesthesia and Critical Care Pritzker School of Medicine, University of Chicago The University of Chicago Medicine Chicago, Illinois Vijaya Gottumukkala, MB, BS, MD, FRCA

Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Basavana G. Goudra, MD, FRCA, FCARCSI Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Andreas Grabinsky, MD

Assistant Professor Department of Anesthesiology University of Washington School of Medicine Harborview Medical Center Seattle, Washington Ashley Greene, DO Resident Physician Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Michael S. Green, DO Assistant Professor Interim Chair Department of Anesthesiology and Perioperative Medicine Drexel University College of Medicine Hahnemann University Hospital Philadelphia, Pennsylvania Alina M. Grigoire, MD, MHS, FASE Associate Professor Director, Division of Cardiothoracic Anesthesiology Department of Anesthesiology University of Maryland School of Medicine University of Maryland Medical Center Baltimore, Maryland Michael Grover, MD Resident Physician

Department of Anesthesiology University of Texas School of Medicine, San Antonio University of Texas Health Science Center at San Antonio San Antonio, Texas Anthony H. Guarino, MD Director, Pain Management Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Vadim Gudzenko, MD

Assistant Clinical Professor Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Maged N. Guirguis, MD Department of Anesthesiology and Pain Management The Cleveland Clinic Cleveland, Ohio Gregory MT Hare, MD, PhD Associate Professor Department of Anesthesia St. Michael’s Hospital Toronto, Canada Jagtar Singh Heir, DO Clinical Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Rachel Helle, DO Resident Physician Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Laura B. Hemmer, MD

Assistant Professor Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois John Henao, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Andrew Herlich, DMD, MD, FAAP

Professor Department of Anesthesiology University of Pittsburgh School of Medicine Chief, UPMC Mercy Pittsburgh, Pennsylvania Ibetsam Hilmi, MBChB, FRCA Associate Professor Department of Anesthesiology Institute of Clinical and Translational Sciences University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Jonathan K. Ho, MD Assistant Clinical Professor Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California John W. Hoffman, Jr., DO, MS Clinical Instructor Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Michael P. Hofkamp, MD Assistant Professor Department of Anesthesiology

Texas A&M, -College of Medicine Scott and White Hospital Temple, Texas Allen Alexander Holmes, MD, MS

Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Joe C. Hong, MD

Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Kimberly Howard-Quijano, MD Clinical Instructor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Tyken C. Hsieh, MD Staff Cardiac Anesthesiologist Department of Anesthesiology Mills-Peninsula Health Services Burlingame, California Angela T. Hsu, MD Attending Physician Department of Anesthesiology Kaiser Permanente Downey, California Eric S. Hsu, MD Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Allen Hu, MD

T. Kate Huncke, MD

Clinical Associate Professor Department of Anesthesiology New York University School of Medicine NYU Langone Medical Center New York, New York Catherine Ifune, MD, PhD

Associate Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Mohamad Iravani, MD Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Selma Ishag, MB, BS, MD Assistant Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri % Jonathan S. Jahr, MD Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Ranu Jain, MD Assistant Professor Assistant Director, Pediatric Anesthesia Department of Anesthesiology The University of Texas School of Medicine at Houston Children’s Memorial Hermann Hospital-Texas Medical Center Houston, Texas Piotr K. Janicki, MD, PhD

Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Richard C. Jensen, MD

Resident Physician Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Rongjie Jiang, MB, MS Resident Physician Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Quinn L. Johnson, MD Assistant Clinical Professor Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Praveen Kalra, MBBS, MD, FCCP Assistant Professor Department of Anesthesiology Oklahoma University College of Medicine Oklahoma University Health Sciences Center Oklahoma City, Oklahoma Mandip S. Kalsi, MD Fellow, Regional Anesthesia Hospital for Special Surgery New York, New York Valbona Kanarek, MD Chief Resident Department of Anesthesiology Mt. Sinai School of Medicine St. Joseph’s Hospital and Regional Medical Center

Paterson, New Jersey Revati Kanekar, MD

Resident Physician Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Ivan M. Kangrga, MD, PhD Associate Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Susan Kaplan, MD Clinical Associate Department of Anesthesiology and Critical Care University of Pennsylvania Philadelphia, Pennsylvania Menelaos Karanikolas, MD, MPH Assistant Professor Department of Anesthesiology Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Keyvan Karkouti, MD, FRCPC, MSc Associate Professor Department of Anesthesia University of Toronto Toronto, Ontario Jeffrey Katz, MD Chief Resident Department of Anesthesia and Critical Care Pritzker School of Medicine, University of Chicago The University of Chicago Medicine Chicago, Illinois Paul Kerby, MB, BS Chief Resident

Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Patrick Kim, MD Resident Physician Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Peter H. Kim, MD Andrew A. Klein, MD Consultant Anaesthesia and Intensive Care Papworth Hospital Cambridge, United Kingdom Antoun Koht, MD Professor of Anesthesiology, Neurological Surgery & Neurology Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois Iosifina Kolliantzaki, MD Department of Anesthesiology Aghia Sophia Children’s Hospital Athens, Greece James J. Konvicka, MD Assistant Professor Department of Anesthesiology Texas A&M College of Medicine Scott and White Healthcare Temple, Texas Edward Kosik, DO John D. Kot, MD

Resident Physician Department of Anesthesiology David Geffen School of Medicine at UCLA

Ronald Reagan Medical Center Los Angeles, California Joseph Koveleskie, MD

Assistant Professor Department of Anesthesiology Tulane University School of Medicine Tulane Medical Center New Orleans, Louisiana Alan J. Kover, MD, PharmD

Clinical Assistant Professor Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Kenneth F. Kuchta, MD Associate Clinical Professor Chief, Vascular Anesthesiology Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Anand Lakshminarasimhachar, MBBS, FRCA Assistant Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Daniel A. Lazar, MD Attending Anesthesiologist North Shore Manhasset Hospital Manhasset, New York Stephane Ledot, MD Hadassah Hebrew University School of Medicine Jerusalem, Israel Thomas Ledowski, MD, PD, DEAA, FANZCA Professor of Anesthesiology University of Western Australia

School of Medicine and Pharmacology Perth, Australia Annie D. Lee, MD

Resident Physician Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Jonathan D. Leff, MD

Assistant Professor Chief, Cardiothoracic Anesthesiology Department of Anesthesiology Albert Einstein College of Medicine Montefiore Medical Center Bronx, New York Philip Levin, MD Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Jinlei Li, MD, PhD Assistant Professor Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Yun Rose Li, BS Medical Student Perelman School of Medicine at the University of Pennsylvania Philadelphia, Pennsylvania Jeffrey W. Lim, MD, PhD Assistant Professor Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut

Sharon L. Lin, MD

Attending Physician Department of Anesthesiology Swedish Medical Center Seattle, Washington Keith E. Littlewood, MD

Associate Professor Vice Chair for Education Department of Anesthesiology Assistant Dean for Clinical Skills Education University of Virginia School of Medicine University of Virginia Health System Charlottesville, Virginia Marc A. Logarta, MD, DABA, FANZCA Consultant Anesthetist Campbelltown Hospital Canterbury Hospital Sydney, Australia David W. Lui, DMD, MD Assistant Professor Department of Oral and Maxillofacial Surgery Virginia Commonwealth University School of Dentistry and School of Medicine VCU Medical Center Richmond, Virginia Calvin Lyons, MD Resident Physician Department of Surgery The Methodist Hospital Houston, Texas Edna Ma, MD Attending Physician Department of Anesthesiology Olive View - UCLA Medical Center Sylmar, California Aman Mahajan, MD, PhD Professor Chief, Cardiothoracic Anesthesiology Vice Chair of Anesthesiology

David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Victor L. Mandoff, MD

Associate Professor Department of Anesthesiology and Critical Care Medicine The University of Arkansas College of Medicine The University of Arkansas for Medical Sciences Little Rock, Arkansas Gerard R. Manecke, Jr., MD

Professor and Chair Department of Anesthesiology University of California, San Diego School of Medicine University of California, San Diego Medical Center San Diego, California Federica Manfroi, MD Michael Mangione, MD

Associate Professor Department of Anesthesiology University of Pittsburgh School of Medicine Chief of Anesthesiology VA Pittsburgh Healthcare System Pittsburgh, Pennsylvania Natesan Manimekalai, MD Assistant Professor Department of Anesthesiology University of Florida College of Medicine Shands Jacksonville Medical Center Jacksonville, Florida Ana Maria Manrique-Espinel, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Brian L. Marasigan, MD Assistant Professor

Residency Program Director Department of Anesthesiology University of Texas Medical School at Houston Memorial Hermann Hospital Houston, Texas Julie Marshall, MD

Assistant Professor Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Jayson T. Maynes, MD, PhD Assistant Professor Hospital for Sick Children/SickKids Research Institute University of Toronto Toronto, Canada Richard McAffee, MD Assistant Professor Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Mary E. McAlevy, MD Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Russell K. McAllister, MD Associate Professor Residency Program Director Department of Anesthesiology Assistant Dean of Quality and Patient Safety Texas A&M College of Medicine Scott & White Memorial Hospital Temple, Texas Dwayne E. McClerkin, MD Assistant Professor

Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Stephen M. McHugh, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Julie McSwain, MD, MPH

Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Li Meng, MD, MPH Associate Professor Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Spyros D. Mentzelopoulos, MD, PhD Assistant Professor Department of Critical Care University of Athens Medical School Athens, Greece David G. Metro, MD Associate Professor Residency Program Director Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Berend Mets, MB, ChB, PhD, FRCA, FFASA Eric A. Walker Professor and Chair Department of Anesthesiology Penn State College of Medicine

Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Tricia A. Meyer, PharmD, MS, FASHP Associate Professor Department of Anesthesiology Director, Department of Pharmacy Texas A&M College of Medicine Scott and White Hospital Temple, Texas Agnes Miller, MD

Director, Resident Education Department of Anesthesiology Maimonides Medical Center New York, New York Sara Miller, MD Resident Physician Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Brian Milne, MD, MSc, FRCPC Professor Department of Anesthesiology and Perioperative Medicine Queen’s University Kingston General Hospital Kingston, Ontario Beth H. Minzter, MD, MS, FIPP Department of Pain Management Anesthesiology Institute The Cleveland Clinic Cleveland, Ohio Nanhi Mitter, MD Assistant Professor Director, Adult Cardiothoracic Anesthesiology Fellowship Department of Anesthesiology and Critical Care Medicine The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland

Kanishka Monis, MD

Fellow, Pain Management Department of Anesthesiology University of Texas School of Medicine, San Antonio University of Texas Health Science Center at San Antonio San Antonio, Texas Richard C. Month, MD

Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Teresa L. Moon, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Kenneth R. Moran, MD Assistant Clinical Professor Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Allyson J.A. Morman, MD Resident Physician Department of Anesthesiology University of Virginia School of Medicine University of Virginia Health System Charlottesville, Virginia Juan Moya-Amor’s, PhD Professor of Surgery Chief, Department of Thoracic Surgery Hospital Universitari de Bellvitge L’Hospitalet de Llobregat Barcelona, Spain Daniel Mulcrone, MD Resident Physician Department of Anesthesiology

University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Eman Nada, MD, PhD

Fellow, Neuroanesthesia The Cleveland Clinic Cleveland, Ohio Carsten Nadjat-Haiem, MD Associate Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Sharanya Nama, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Gundappa Neelakanta, MD Clinical Professor of Anesthesiology Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Jacques Prince Neelankavil, MD Assistant Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Eric W. Nelson, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina

Sara C. Nelson, MD

Attending Physician Department of Anesthesiology Naval Medical Center San Diego San Diego, California Edward C. Nemergut, MD

Associate Professor of Anesthesiology and Neurosurgery University of Virginia School of Medicine University of Virginia Health System Charlottesville, Virginia Anh-Thuy Nguyen, MD

Associate Clinical Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Linh Trang Nguyen, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Teodora Orhideea Nicolescu, MD Associate Professor Chief, Division of Cardiothoracic Anesthesiology Department of Anesthesiology Oklahoma University College of Medicine Oklahoma University Health Sciences Center Oklahoma City, Oklahoma Daniel R.C. Nieva, MD Assistant Professor Department of Anesthesiology Washington University School of Medicine St. Louis Children’s Hospital St. Louis, Missouri Dave Nisha Davendra, PharmD, DO Assistant Clinical Professor Department of Anesthesiology Mount Sinai School of Medicine St. Joseph’s Hospital and Regional Medical Center

Paterson, New Jersey Mark E. Nunnally, MD, FCCM

Associate Professor Department of Anesthesia and Critical Care Pritzker School of Medicine, University of Chicago The University of Chicago Medicine Chicago, Illinois Satoru Ogawa, MD Department of Anesthesiology Emory University School of Medicine Emory University Hospital Atlanta, Georgia Olutoyosi Ogunkua, MD Resident Physician Department of Anesthesiology and Pain Management University of Texas Southwestern School of Medicine University of Texas Southwestern Medical Center at Dallas Dallas, Texas Erik Olness, MD Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia Onyi Onuoha, MD, MPH Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Todd M. Oravitz, MD Associate Professor Chief, Liver Transplantation Anesthesiology Department of Anesthesiology The University o Pittsburgh School of Medicine VA Pittsburgh Healthcare System Pittsburgh, Pennsylvania

Pascal O. Owusu-Agyemang, MD

Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Nirvik Pal, MD

Clinical Instructor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Edward Park, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Dorothea Rosenberger Parravano, MD, PhD Associate Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Andrea Parsons, MD Assistant Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Parisa Partownavid, MD Associate Clinical Professor Associate Director, Ambulatory Surgery Center Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Mitesh Patel, MD Chief Resident

Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Neesa Patel, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Shetal H. Patel, MD

Fellow, Obstetric Anesthesiology Department of Anesthesiology Charles Drew University of Medicine and Science Cedars-Sinai Medical Center Los Angeles, California Swati Patel, MD Clinical Professor of Anesthesiology Chief, Division of Pediatric Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Tara L. Paulose, MD Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Katerina Pavenski, MD, FRCPC Department of Laboratory Medicine St. Michael’s Hospital, Toronto, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, Canada Alison R. Perate, MD Assistant Professor Department of Anesthesiology Perelman School of Medicine at the University of Pennsylvania Children’s Hospital of Philadelphia Philadelphia, Pennsylvania

Lauren Mai Pieczynski, MD

Resident Physician Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Raymond M. Planisic, MD

Professor of Anesthesiology Director, Transplantation Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Keyuri Popat, MD Associate Professor Department of Anesthesiology and Pain Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Wanda M. Popescu, MD Associate Professor of Anesthesiology Yale-New Haven Hospital New Haven, Connecticut Marek Postula, MD, PhD Assistant Professor at the Department of Experimental and Clinical Pharmacology Medical University of Warsaw Senior Assistant at the Department of Noninvasive Cardiology and Hypertension Central Clinical Hospital The Ministry of the Interior Warsaw, Poland Debra Domino Pulley, MD Associate Professor Department of Anesthesiology and Pain Medicine Washington University of School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Carlos A. Puyo, MD Assistant Clinical Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine

Barnes-Jewish Hospital St. Louis, Missouri Farooq A. Qureshi, MD

Fellow, Pain Management Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Henry Ra, MD

Resident Physician Department of Anesthesiology and Critical Care Medicine David Geffen School of Medicine at UCLA Ronald Reagan Hospital Center Los Angeles, CaliforniaFabrizio Racca, MD S.C. Anestesia e Rianimazione Pediatrica Azienda Ospedaliera SS Antonio Biagio e Cesare Arrigo Alessandria, Italy Siamak Rahman, MD Associate Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Niraja Rajan, MB, BS, FAAP Assistant Professor Medical Director, Hershey Outpatient Surgery Center Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Sivam Ramanathan, MD Associate Professor of Anesthesiology Charles Drew University of Medicine and Science Cedars-Sinai Medical Center Los Angeles, California Chitra Ramasubbu, MD

Fellow, Pain Management Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland George J. Ranier, MD

Assistant Professor Department of Anesthesiology West Virginia University School of Medicine Robert C. Byrd Health Sciences Center Morgantown, West Virginia V. Marco Ranieri, MD Universita di Torino Dipartimento di Discipline Medico-Chirurgiche Sezione di Anesthesiologia e Rianimazione Ospedale S. Giovanni Battista Torino, Italy Srikantha L. Rao, MBBS, MS Associate Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Rashmi R. Rathor, MD Fellow, Abdominal Organ Tranplant Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Elizabeth Rebello, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Venugopal S. Reddy, MD, EDIC, FFARCS Associate Professor Department of Anesthesiology Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania Rebecca L. Reeves, DO

Resident Physician Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Wendy HP Ren, MD, FAAP Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan UCLA Medical Center Los Angeles, California Joseph Resti, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Cameron J. Ricks, MD Assistant Professor Department of Anesthesiology and Perioperative Care University of California, Irvine School of Medicine University of California, Irvine Douglas Hospital Irvine, California Horst Rieke, MD, PhD Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Francisco Rivas-Doyague, MD Medical Doctor Department of Thoracic Surgery Hospital Universitari de Bellvitge L’Hospitalet de Llobregat Barcelona, Spain

Laura L. Roberts, MD

Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Adam Romanovsky, MD

Assistant Clinical Professor Divisions of Critical Care and Nephrology University of Alberta Edmonton, AB Canada Harvey K. Rosenbaum, MD Clinical Professor of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan UCLA Medical Center Los Angeles, California Jay A. Roskoph, MD, MBA Clinical Assistant Professor Department of Anesthesiology University of Pittsburgh School of Medicine Chief Department of Anesthesiology UPMC-St. Margaret Hospital Pittsburgh, Pennsylvania Marc A. Rozner, PhD, MD Professor of Anesthesiology and Perioperative Medicine Professor of Cardiology University of Texas MD Anderson Cancer Center Houston, Texas Daniel M. Rusu, MD Assistant Professor Department of Anesthesia and Critical Care University of Kentucky College of Medicine University of Kentucky Healthcare Lexington, Kentucky Ali Salehi, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA

Ronald Reagan Medical Center Los Angeles, California Alain A. Salvacion, MD

Fellow, Cardiothoracic Anesthesia Department of Anesthesiology Feinberg School of Medicine, Northwestern University Northwestern Memorial Hospital Chicago, Illinois Samuel Samuel, MD

Associate Fellowship Director of Pain Management The Cleveland Clinic Cleveland, Ohio Mona G. Sarkiss, MD, PhD Associate Professor Department of Anesthesiology and Perioperative Medicine Department of Pulmonary Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Poovendran Saththasivam, MD Resident Physician Department of Anesthesiology Drexel University College of Medicine Hahnemann University Hospital Philadelphia, Pennsylvania Matthew V. Satterly, MD Fellow, Pain Management Department of Anesthesia and Critical Care Pritzker School of Medicine, University of Chicago The University of Chicago Medicine Chicago, Illinois Shashank Saxena, MD Clinical Assistant Professor Department of Anesthesiology University of Pittsburgh School of Medicine Staff Anesthesiologist VA Pittsburgh Health Care System Pittsburgh, Pennsylvania

R. Alexander Schlichter, MD

Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Peter M. Schulman, MD

Assistant Professor Department of Anesthesiology and Perioperative Medicine Oregon School of Medicine Oregon Health and Science University Portland, Oregon Jeffrey J. Schwartz, MD Associate Professor Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Johanna C. Schwarzenberger, MD Clinical Professor Director, Pediatric Cardiac Anesthesiology Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Korrin Scott, MD Resident Physician Department of Anesthesiology University of Virginia School of Medicine University of Virginia Health System Charlottesville, Virginia Jennifer Scovotti, MA Research Associate Department of Anesthesiology David Geffen School of Medicine at UCLA Los Angeles, California Khaled Sedeek, MD Associate Professor

Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania E. Gail Shaffer, MD, MPH Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Kirk H. Shelley, MD, PhD

Professor Department of Anesthesiology Yale School of Medicine Yale-New Haven Hospital New Haven, Connecticut Justin C. Shields, MD Resident Physician Department of Anesthesiology Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Shawn T. Simmons, MD Associate Clinical Professor Medical Director, Hyperbaric Medicine Service Department of Anesthesia University of Iowa Carver College of Medicine University of Iowa Hospitals Iowa City, Iowa Amrik Singh, MD Associate Professor Residency Program Director Department of Anesthesiology and Pain Medicine University of California, Davis School of Medicine UC Davis Medical Center Sacramento, California Davinder Singh, MD Assistant Professor

Department of Anesthesiology and Perioperative Care University of California, Irvine School of Medicine University of California, Irvine Douglas Hospital Irvine, California Sukhdip Singh, MD Resident Physician Department of Anesthesiology University of Pittsburgh School of Medicine University of Pittsburgh Medical Center Pittsburgh, Pennsylvania Sumit Singh, MD

Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Nina Singh-Radcliff, MD Assistant Clinical Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Christopher A. Skorke Assistant Professor Medical Director, Medical/Surgical ICU Department of Anesthesiology and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Jose M. Soliz, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Dmitri Souzdalnitski, MD, PhD Pain Management Department The Cleveland Clinic Cleveland, Ohio

Martin M. Stechert, MD

Associate Clinical Professor Department of Anesthesiology and Perioperative Care University of California, San Francisco School of Medicine UCSF Medical Center San Francisco, California Chris A. Steel, MD

Attending Physician Director of Anesthesia Services White River Health System Batesville, Arizona Jacob Steinmetz, MD, PhD Consultant Department of Anesthesia Copenhagen University Hospital Rigshospitalet, Copenhagen Jochen Steppan, MD Fellow, Cardiothoracic Anesthesia Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Joel Stockman, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California William David Stoll, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Bradley A. Stone, MD Attending Anesthesiologist Mission Hospital Asheville, North Carolina

Suzanne Strom, MD

Assistant Clinical Professor Residency Program Director Department of Anesthesiology and Perioperative Care University of California, Irvine School of Medicine University of California, Irvine Douglas Hospital Irvine, California Adam M. Stuart, MD

Medical Student Virginia Commonwealth University School of Medicine Richmond, Virginia Mariya Svilik, MD Staff Physician Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Rajeshwary Swamidurai, MD Attending Physician Department of Anesthesiology Lodi Memorial Hospital Lodi, California Kenichi A. Tanaka, MD, MSc Associate Professor Department of Anesthesiology Emory University School of Medicine Atlanta, Georgia Rob C. Tanzola, MD, FRCPC Assistant Professor Department of Anesthesiology and Perioperative Care Queen’s University Kingston General Hospital Kingston, Ontario Vijay Tarnal, MBBS, FRCA Clinical Assistant Professor Department of Anesthesiology The University of Texas Medical Branch School of Medicine at Galveston The University of Texas Medical Branch at Galveston

Galveston, Texas Adam Thaler, DO

Resident Physician Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Ilka Theruvath, MD, PhD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Svjetlana Tisma-Dupanovic, MD Assistant Professor Department of Cardiology Kansas University School of Medicine Kansas University Medical Center Kansas City, Kansas Catherine Dawson Tobin, MD Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Lan Chi Tran, MD Resident Physician Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Timothy T. Tran, MD Resident Physician Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri

Ravi S. Tripathi, MD

Assistant Clinical Professor Department of Anesthesiology The Ohio State University College of Medicine The Ohio State University Wexner Medical Center Columbus, Ohio Angela Truong, MD

Associate Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Dam-Thuy Truong, MD Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas January Y. Tsai, MD Assistant Clinical Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Judith A. Turner, MD, PhD Assistant Clinical Professor Residency Program Director Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Kalpana Tyagaraj, MD Residency Program Director Director, Obstetric Anesthesiology Department of Anesthesiology Maimonides Medical Center New York, New York Shital Vachhani, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine The University of Texas MD Anderson Cancer Center

Houston, Texas Dierk A. Vagts, MSc, DEAA, EDIC

Professor Department of Anesthesiology and Intensive Care Medicine, Emergency Medicine, Pain Therapy and Palliative Care Academic Teaching Hospital of Johannes Gutenberg University Mainz, Neustadt Weinstrasse, Germay Sonia Vaida, MD Professor of Anesthesiology, Obstetrics and Gynecology Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Elizabeth Valentine, MD Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Andrea Vanucci, MD, DEAA Assistant Professor Department of Anesthesiology Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Swarup S. Varaday, MBBS, FRCA, FCARSI Assistant Professor Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Malina M. Varner, MD Instructor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania

Aditya Venkataraman, MD

Chief Resident Department of Anesthesiology and Pain Medicine Washington University School of Medicine Barnes-Jewish Hospital St. Louis, Missouri Thomas Verbeek, MBChB

Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Bruce Vrooman, MD Department of Pain Management Cleveland Clinic Cleveland, Ohio Samuel H. Wald, MD Clinical Professor Department of Anesthesiology and Critical Care David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Cynthia Wang, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Ellen Y. Wang, MD Clinical Assistant Professor Department of Anesthesiology Stanford University Lucile Packard Children’s Hospital Palo Alto, California Steve Wang, MD Assistant Professor Department of Anesthesiology and Pain Medicine University of Texas MD Anderson Cancer Center

Houston, Texas Izabela M. Wasiluk, MD

Assistant Professor Department of Anesthesiology University of Florida College of Medicine Shands Jacksonville Medical Center Jacksonville, Florida Huafeng Wei, MD, PhD Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Jiadong Wei, MD Yoram G. Weiss, MD, MBA, FCCM Associate Professor in Anesthesiology and Critical Care Medicine Hadassah Hebrew University School of Medicine Jerusalem, Israel Adjunct Associate Professor Department of Anesthesiology and Critical Care University of Pennsylvania Philadelphia, Pennsylvania Gregory E. R. Weller, MD, PhD Assistant Professor Department of Anesthesiology Penn State College of Medicine Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania Joseph R. Whiteley, DO Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina J. Aaron Williams, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine

University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Sylvia H. Wilson, MD

Assistant Professor Department of Anesthesia and Perioperative Medicine The Medical University of South Carolina MUSC Medical Center Charleston, South Carolina Stephen P. Winikoff, MD

Professor Department of Anesthesiology Mount Sinai School of Medicine St. Joseph’s Hospital and Regional Medical Center Paterson, New Jersey Jeremy Wong, MD Assistant Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Christopher Wray, MD Assistant Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Jennifer Wu, MD, MBA Assistant Professor Department of Anesthesiology University of Texas Medical School at Houston Memorial Hermann Hospital Houston, Texas Sulin G. Yao, MD Attending Physician Department of Anesthesiology Atlanticare Regional Medical Center Pomona, New Jersey

Peter K. Yi, MD

Assistant Professor Department of Anesthesiology and Critical Care Perelman School of Medicine at the University of Pennsylvania Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Dirk Younker, MD

Russell D and Mary B Sheldon Professor of Anesthesiology Vice Chairman for Clinical Affairs Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Zdravka Zafirova, MD Assistant Professor Department of Anesthesia and Critical Care Pritzker School of Medicine, University of Chicago The University of Chicago Medicine Chicago, Illinois Alan P. Zaggy, MD Assistant Professor Department of Anesthesiology and Perioperative Medicine University of Missouri School of Medicine University of Missouri Health System Columbia, Missouri Mark Zakowski, MD Associate Professor of Anesthesiology, Adjunct Charles Drew University of Medicine and Science Chief, Obstetric Anesthesiology Cedars-Sinai Medical Center Los Angeles, California Sherif Zaky, MD, PhD Assistant Professor of Anesthesiology The Cleveland Clinic Cleveland, Ohio Sessunu M. Zemo, MD Resident Physician Department of Anesthesiology

Baylor College of Medicine Ben Taub Hospital Houston, Texas Fei Zheng, MD, MPH, MS

Resident Physician Department of Anesthesiology The Johns Hopkins University School of Medicine The Johns Hopkins Hospital Baltimore, Maryland Dayna Zimmerman, BS

Research Assistant Department of Anesthesiology David Geffen School of Medicine at UCLA Los Angeles, California Keren Ziv, MD Associate Clinical Professor Department of Anesthesiology David Geffen School of Medicine at UCLA Ronald Reagan Medical Center Los Angeles, California Zachary M. Zumbar, MD, MPH Attending Physician Midwest Pain Physicians Uniontown, Ohio

FOREWORD

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t is a pleasure to introduce the 5 Minute Anesthesia Consult to readers around the globe. This concise compendium of topics pertinent to modern anesthesiology practice will be useful as a rapid reference for busy anesthesiology clinical practitioners, anesthesiology residents, medical students and others in training, nurse anesthetists, anesthesiology assistants, perioperative nurses, post-operative intensive care personnel, and other allied health professionals caring for patients before and after anesthetic administration. The contents are offered in both text format as well as applications for smart devices, to be readily at hand in any clinical situation in any clinical location.

The editor has drawn from a wide spectrum of expert authors from multiple institutions to compile approximately 480 two-page chapters, in template formats for easy-to-retrieve information. The content is organized into sections on important topics in physiology, pertinent issues for major co-existing diseases/co-existing conditions, key information for important surgical procedures, and guidance for managing a variety of complications encountered in anesthetic practice. In addition, the 5 Minute Anesthesia Consult contains a drug section in a condensed, easily accessible format with current information about anesthetic drugs and adjuvants, chronic medications that patients may be taking in the perioperative period, and medications used to treat complications encountered in the perianesthetic period. As anesthesiology care is extending to encompass the spectrum from early evaluation and optimization/management of pre-procedural risk factors, through post-procedural care to minimize subsequent complications and/or re-admission, every practitioner can benefit from timely access to a “one-stop” content source to support evidence-based anesthesiology care, a source that concisely presents the most important concepts on a topic in an accessible manner. I look forward with enthusiasm to the broad distribution and availability of the 5 Minute Anesthesia Consult to support high quality patient outcomes on an international basis. PATRICIA A. KAPUR, MD Professor and Chairwoman Department of Anesthesiology David Geffen School of Medicine at UCLA Los Angeles, California, USA April 2012

PREFACE

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he 5 Minute Medicine Consult was amongst the medical texts and references that lined my mother’s bookshelf when I was in high school. I was drawn to the unique style that made it “easy to read,” even at my level. The topic-specific and highly templated format was the first of its kind amongst medical references. Years later, I have been given the amazing opportunity to add to The 5 Minute Consult Series.

The goal of The 5 Minute Anesthesia Consult is to emulate that style by creating an evidence-based, focused, and practical textbook that will be relevant to students, trainees, nurse anesthetists, and physicians. The 480 topics are presented alphabetically, but are presented in a second table of contents organized in four sections: Physiology, Co-Existing Disease, Surgical Procedure, and Management. Each topic follows a two-page outline format that is consistent with the section and easy to read. Additionally, we have provided a focused Drug section. The chapters in the Physiology section were specifically written to simplify complex topics and then extrapolate them to pathophysiologic processes and apply them to relevant perioperative matter. The Surgical Procedures section describes key surgical steps, followed by anesthetic considerations for preoperative preparation, intraoperative care, and postoperative concerns. The goal of this section is to “involve” the anesthesia practitioner in the surgical procedure by providing an understanding of, and appreciation for, our surgical colleagues’ work. The chapters in the Co-Existing Disease Section describe basic pathophysiology concepts, followed by key considerations to optimizing and managing patients throughout the perioperative period.

The Management Section covers a comprehensive list of perioperative complications that can arise in anesthetic practice. For example, the author of the Anaphylaxis chapter had a patient who “crumped” after being exposed to medication. Despite appropriately treating the patient with epinephrine and following ACLS protocol, the patient remained unresponsive to therapy. The author saved her patient’s life by administering glucagon, which she describes in her chapter as the treatment for refractory anaphylaxis that may be seen in patients who are beta-blocked. Each chapter provides a list of additional complementary topics that are available within the book to allow readers the opportunity to supplement their knowledge of a given topic. I sincerely hope that the practical nature and quality of this text will contribute to your learning and benefit our patients in the ever-growing field of anesthesia. I welcome feedback and suggestions at [email protected].

ACKNOWLEDGEMENTS

T

he completion of this text would not have been possible without a number of special people. The authors have given their time and expertise to prepare, revise, and re-revise their chapters to attain the overarching vision for this textbook. I enjoyed the opportunity to meet (and learn from) so many talented and enthusiastic practitioners and teachers, as well as work with so many of my close friends, colleagues, former attendings, and mentors. I would like to express my utmost gratitude for their quality contributions; their work has resulted in what I believe is one of the best anesthesia texts out there. My Publisher, Brian Brown, Senior Product Manager, Nicole Dernoski, and Lippincott Williams & Wilkins/Wolters Kluwer Health provided me with mentorship, a team of highlevel professionals, and invaluable resources. I would like to thank them for providing me with this tremendous opportunity to expand the highly successful 5 Minute Consult Series. Thank you Drs. Patricia A. Kapur, Randy Steadman, Sam Wald, Rima Matevosian, Susan Chan, Jordan Miller, Aman Mahajan, Barbara Van de Wiele, Phil Levin, Victor Duval, Nir Hoffman, Carsten Nadjat-Haiem, Keren Ziv, Eric Hsu, Kenneth Kuchta, Michael Ferrante, Michelle Braunfeld, Zhuang Fang, Swati Patel, Mitchell Lin, Michael Sopher, Ali Salehi, Siamak Rahman, Parisa Partownavid and the UCLA Department of Anesthesiology for teaching me to think critically, being patient, and serving as role-models. Your efforts, dedication, and love for teaching and your patients have had far-reaching influences on me.

12 LEAD EKG

Elizabeth Valentine, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• The 12-lead EKG is a noninvasive test that provides information on the electrical function of the heart and aids in the diagnosis of pathophysiologic processes. • Serves as a baseline for perioperative changes and as a screening tool to identify cardiac abnormalities. • Continuous 3- or 5-lead EKG is an American Society of Anesthesiologists (ASA) standard monitor used for general anesthesia and monitored anesthesia care. PHYSIOLOGY PRINCIPLES

• P wave (80 ms): Denotes atrial depolarization. Myocardial depolarization is normally initiated by spontaneous sinoatrial (SA) node depolarization. The signal is quickly and efficiently conducted along a specialized conduction pathway. In the atria, this pathway is via interatrial tracts (anterior, middle, and posterior); they begin by depolarizing the right, followed by the left, atria. The conduction cells depolarize adjacent myocardial cells, which have a different histology. • QRS (80–120 ms): Denotes the varying stages of ventricular depolarization. The Q wave is the initial negative deflection and results from septal depolarization. The R wave follows and is the first positive deflection. It results from depolarization of the larger, more muscular left ventricle; right ventricular depolarization is normally obscured. The S wave is the final negative deflection caused by lateral wall depolarization. • T wave: Denotes ventricular repolarization. The beginning of the wave represents a period of absolute refractoriness, where a subsequent depolarization (no matter how strong) cannot initiate a aberrant rhythm. The latter portion of the wave is a time of relative refractoriness, where a strong enough depolarization can result in a runaway rhythm. • PR interval (120–200 ms): Time from the start of atrial depolarization to atrioventricular (AV) nodal conduction to conduction through the His-Purkinje system. • QRS width: Represents the time for ventricular depolarization • J point: Describes the intersection between the QRS complex and ST segment. When the heart rate is increased, atrial repolarization may be observed at the very end of the QRS complex as J point depression. • ST segment: Denotes the end of depolarization to the beginning of repolarization and is usually isoelectric • QT interval (QTc <440 ms): Beginning of ventricular depolarization to the end of ventricular repolarization. Time for ventricular repolarization is heart rate dependent; thus, the QT is usually corrected for heart rate (QTc). • Rate: Typically measured between sequential R waves; the RR interval (0.6–1.2 s) is useful

due to its prominent wave that allows for easy detection. A rate <60 bpm is bradycardia; a rate >100 bpm is tachycardia. • Rhythm: The location of regular P waves preceding each QRS suggests an atrial rhythm. The relationship between the P wave and QRS complex provides information about underlying conduction defects or dissociation. • Axis: The average direction of the various complexes determines the axis. The normal QRS axis is between 0 and 100° in the frontal plane. Left or right axis deviation can suggest underlying pathophysiology.

ANATOMY

• A total of 12 leads allows for “visualizing” the electrical function from different angles through the heart. Considering the leads in different combinations can aid in clinical diagnosis. • Standard limb leads (I, II, III): Form the points of Einthoven’s triangle, an equilateral triangle whose vertices lie at the left and right shoulders and the pubic region and whose center corresponds to the vector sum of all electric activity occurring in the heart at any given moment. This allows for the determination of the electrical axis. • Augmented limb leads (aVR, aVL, aVF): Together with the standard limb leads, record the electrical activity along the frontal plane. • Precordial leads (V1, V2, V3, V4, V5, V6): Record the electrical activity along the horizontal plane. • Anterior leads (V3 and V4): Allow evaluation and assessment of the electrical function of the anterior wall of the heart. Usually supplied by the left anterior descending artery. • Inferior leads (II, III, and aVF): Allow evaluation and assessment of the electrical function of the inferior heart muscle. The inferior wall is usually supplied by the right coronary artery.

DISEASE/PATHOPHYSIOLOGY

• ST segments: Ischemia or infarct may present as either elevation or depression of the ST segment. A routine preoperative EKG may appear normal if a patient is not experiencing active ischemic symptoms. Thus, a high index of suspicion must be maintained for patients at risk for coronary ischemia. • Axis deviation: Common conditions associated with left axis deviation include left bundle branch block or left anterior hemiblock, inferior MI, or left ventricular hypertrophy. Common causes of a right axis deviation include right ventricular hypertrophy, chronic lung disease, right bundle branch block, or lead reversal. • Bundle branch blocks: A prolonged QRS suggests either a right (RBBB) or a left bundle branch block (LBBB). They are described as either partial (QRS <120 ms) or complete (QRS >120 ms). Although a RBBB can represent pulmonary or right heart disease, it is more commonly benign. Alternatively, a LBBB is more likely to indicate underlying cardiac pathology (CAD, CMO, valvular disease). A new onset LBBB should prompt a thorough cardiac workup. The anterior or posterior fascicle of the left bundle may be blocked in isolation (termed hemiblock). A nonspecific intraventricular conduction delay describes a nonpathologic widening of the QRS complex that does not meet the criteria for either LBBB or RBBB. • AV blocks: Impaired conduction between the atria and ventricles of the heart are described

as first, second, and third degree. First-degree AV block is defined as a PR interval >0.2 s. Second-degree AV block may be Type 1 (Mobitz 1, Wenckebach), defined as progressive prolongation of the PR interval with eventual dropped QRS; or Type II (Mobitz 2), where the PR remains unchanged prior to the sudden failure of conduction of a P wave and a dropped ventricular beat. In third-degree AV block, there is no association between P waves and QRS complexes. While first-degree and Mobitz I AV block are generally benign conditions, Mobitz II (can progress to complete heart block) and third-degree AV blocks are indications for cardiac pacing. • P waves: Abnormal P wave morphology may indicate an ectopic atrial rhythm, whereas a changing P wave morphology may suggest either a wandering atrial pacemaker or multifocal atrial tachycardia. An irregular rhythm with no clear P waves suggests atrial fibrillation. A regular “saw tooth” pattern may suggest atrial flutter. • Arrhythmias: A narrow QRS suggests a supraventricular (above the ventricles) rhythm while a wide QRS suggests either a ventricular source or aberrant conduction of a supraventricular rhythm. • QT prolongation: Prolonged QTc is a risk factor for developing ventricular arrhythmias (Torsades de Pointes) and is an independent risk factor for sudden cardiac death. QTc may be prolonged due to genetic causes (long QT syndrome), drugs (haloperidol, methadone), or diseases (hypothyroidism). • Delta waves: Describes a slurred upstroke of the QRS complex and is found in patients with Wolff–Parkinson–White (WPW) syndrome. WPW is caused by the bypass of the AV node via an accessory pathway called the bundle of Kent. This accessory pathway does not have the rate-slowing property of the AV node, thus allowing for extremely fast heart rates and potential hemodynamic instability. The combination of cardiac arrhythmias and an accessory pathway may degenerate into ventricular fibrillation. • R on T phenomenon: The beginning of the T wave is a time of absolute refractoriness; the latter portion of the wave is a time of relative refractoriness. An abnormal depolarization signal (aberrant pacemaker, PAC, PVC, cardioversion) cannot depolarize the entire ventricle during the absolute refractory period; however, it may potentially do so during the relative refractory period. This can result in degeneration into ventricular tachycardia or fibrillation. • Artificial pacemaker: May be identified by tell-tale “pacer spikes” on EKG or telemetry. May be atrial, ventricular, or sequentially paced. QRS will appear widened if ventricularly paced. • Medication toxicities: – Digoxin: Characteristic downward sloping of the ST segment. May also see an increased PR and decreased QTc interval. – Tricyclic antidepressants (TCAs): Characteristic rightward change in the frontal plane QRS vector. A large R wave in aVR is quite sensitive for TCA toxicity; may also see an increased QRS and QTc interval. • Electrolyte abnormalities: – Hypokalemia: EKG changes result from delayed ventricular repolarization. May include T wave flattening and/or inversion, ST segment depression, prominent U wave, increased P wave amplitude, and prolonged PR interval. Increased myocardial cell automaticity may predispose to atrial or ventricular arrhythmias. – Hyperkalemia: EKG changes are due to delayed depolarization and hastened

repolarization. Changes commonly progress in order from symmetrically peaked T waves → widened QRS → prolonged PR interval → loss of P wave → loss of R wave → ST depression → EKG that resembles sine wave → ventricular fibrillation → asystole. – Hypocalcemia: QTc prolongation and cardiac irritability leading to arrhythmias – Hypercalcemia: Shortened ST segment and QTc interval – Hypomagnesemia: PR and QT interval prolongation, cardiac irritability – Hypermagnesemia: May see PR prolongation and QRS widening

PERIOPERATIVE RELEVANCE

• Intraoperative bovie, electrical interference, patient shivering, tremors, or movement may closely resemble an intraoperative arrhythmia. Close inspection may reveal the QRS “marching through” the interference; other times, it may be indistinguishable from a true arrhythmia. Close evaluation of other monitors (blood pressure, pulse oximetry or arterial plethysmograph, verification of palpable peripheral pulses) may provide clues in this circumstance. • Malpositioning of leads may result in the appearance of ST changes. Thus, it is good practice to place leads in proper position if it does not interfere with the surgical field and to note baseline abnormalities in the EKG tracing. • Body habitus: Large breasts or obesity may result in low-voltage EKG. • Pulmonary artery catheters and central lines: For patients with LBBB, there is a risk of complete heart block with insertion. In this circumstance, it is prudent to have pacing capabilities readily available. Similarly, in patients with WPW, the pulmonary artery catheter or a wire for central line placement can induce a hemodynamically intolerable tachyarrhythmia. • Extracorporeal shock wave lithotripsy: Older machines time shocks to be delivered during the R wave to prevent R on T phenomenon. • Cardioversion: Machines synchronize the delivery of electrical discharge to the R wave to prevent R on T phenomenon.

GRAPHS/FIGURES

FIGURE 1. EKG waves, segments, and intervals

FIGURE 2. The 12 leads allow for assessment of the electrical function of the three-dimensional heart.

REFERENCES

1. Correll DJ, Hepner DL, Chang C, et al. Preoperative electrocardiograms: Patient factors predictive of abnormalities. Anesthesiology. 2009;110(6):1217–1222. 2. Eagle KA, Berger PB, Calkins H, et al. Practice advisory for preanesthesia evaluation: An updated report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. Anesthesiology. 2012;116:522–538.

ADDITIONAL READING

• ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery. Circulation. 2002;105:1257–1267. • Guidelines for electrocardiography: A report of the American College of Cardiology/American Heart Association Task Force on assessment of diagnostic and therapeutic cardiovascular procedures. J Am Coll Cardiol. 1992;19:473–481.

See Also (Topic, Algorithm, Electronic Media Element) • Myocardial ischemia • QT prolongation • Wolff–Parkinson–White (WPW) syndrome • Cardiac action potentia • Coronary arteries

CLINICAL PEARLS

• The axis of lead II is parallel to that of atrial depolarization; thus, it has the largest P wave and helps to determine rhythm. Lead II also represents the inferior wall of the left ventricle, which is typically supplied by the right coronary artery. EKG abnormalities in this area may suggest ischemia or disease in this distribution. • Lead V5 is most sensitive for detecting ST segment changes when a single lead is monitored

(detects abnormalities in 75% of cases). The combination of monitoring leads V5 and II increases sensitivity to 80% and leads V4 and V5 increases sensitivity to 90% for detecting intraoperative ST changes (1). • Preoperative guidelines: The ASA Task Force on Preanesthesia Evaluation does not support the ordering of any routine preoperative testing; instead, preoperative tests should be ordered on a selective basis based on patient history, exam, and surgical risk factors (2). – Important clinical factors that may make preoperative EKG evaluation useful include cardiovascular diseases (CAD, CHF, significant valvular disease), respiratory diseases (COPD, OSA, lung cancer), or highly invasive procedures. – While age >65 years old is an independent predictor for significant preoperative EKG abnormalities, there was no consensus minimum age for asymptomatic patients undergoing low-risk procedures, or in low-risk patients. • Preoperative EKG may be useful in risk-stratification in intermediate-risk and high-risk surgical patients for predicting cardiovascular death. An abnormal EKG in patients with documented CAD or at high risk for CAD and undergoing major noncardiac surgery was shown to predict long-term outcome.

ABDOMINAL AORTIC ANEURYSM Adam M. Thaler, DO Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• The normal aortic diameter is approximately 20 mm (2 cm). The aorta is considered widened, dilated, or aneurismal when it increases to 1.5 times the normal diameter. • Patients may present perioperatively for aneurismal repair as well as for nonvascular surgeries with a known (or unknown) diagnosis of an abdominal aortic aneurysm. EPIDEMIOLOGY Incidence

• 12–19% of patients with an AAA have a first-degree relative with a history of AAA. • Total incidence in the adult population: 2–4%

Prevalence

• Approximately 90% of AAAs that are found incidentally on screening are <3.5 cm. • Most common age 65–75 years • Male:female 7:1 • Infrarenal aneurysms comprise ∼90% of AAAs.

Mortality

• Mortality: Ruptured AAA is the 13th leading cause of death in the US, causing an estimated 15,000 deaths per year. • AAA rupture is usually fatal (70–80%) and only 50% present to the hospital alive.

ETIOLOGY/RISK FACTORS

• Chronic smokers (4 times more likely than nonsmokers) (1) • Male gender • Atherosclerosis • Hypertension • Marfan syndrome, Ehlers–Danlos syndrome, syphilis, trauma, mycotic infection (rare causes)

PATHOPHYSIOLOGY

• The extracellular matrix is comprised of elastin and collagen, which provides tensile strength. Tensile strength is defined as the maximum stress that a material can withstand while being stretched or pulled before being deformed or broken. Thus, they provide a necessary function to the aorta—to endure the pulsatile, high pressures of blood being ejected from the left ventricle. • The pathogenesis of aneurysms involves alterations in the connective tissue of the aortic

wall. It has been proposed that adventitia elastin degradation is a primary, and hallmark, event that leads to AAA formation; collagen disruption is the ultimate cause of rupture. • Inflammation is believed to play a role with macrophages and T lymphocytes capable of: – Producing proteolytic enzymes that can cause protein degradation – Causing smooth muscle apoptosis – Releasing pro-inflammatory cytokines • Degradation that results in weakening of the aortic wall and aneurysmal development can result from a number of different causes: – Arteriosclerosis most commonly affects the abdominal aorta (compared to the thoracic). It is also more likely to result in aneurysm (compared to stenosis in the infrarenals). – Infection • Laplace’s law states that T = (R × ΔP)/H, where T is tension, R is radius, ΔP is change in pressure, and H is wall thickness. Thus, vessel diameter widening, increased arterial pressures, and decreased wall thickness result in increased tension; the increased tension can serve to further exacerbate the size of the aneurysm. • Morphology: A fusiform aneurysm has a fairly uniform shape, with symmetrical dilation that involves the full circumference of the aortic wall. Saccular aneurysms have a localized dilation that appears as an outpouching of only a portion of the aortic wall. A pseudoaneurysm is not an aneurysm, but instead, is a well-defined collection of blood and connective tissue outside the vessel wall.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients with a diagnosis of AAA often have comorbid cardiovascular conditions such as cerebrovascular, coronary, or renal disease. • Both the size and rate of growth of aneurysm are important when determining the need for intervention.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Usually asymptomatic • Expanding AAA may present with abdominal or back pain (due to pressure on surrounding tissues) or pain in the legs (due to disturbed blood flow). • Ruptured AAA: Classic triad (hypotension, back pain, pulsatile abdominal mass) presents in only 1/2 of patients.

History

• How and when the AAA diagnosed; any change in size, current plan of treatment • Risk factors • Comorbid conditions; patients are considered “vasculopaths” and disease in other vessels should be considered until proven otherwise.

Signs/Physical Exam

Presence of an abdominal bruit or lateral propagation of the aortic pulse wave offers subtle clues and may be more frequently found than a pulsatile mass.

MEDICATIONS

• No medical therapy has been found to be effective at decreasing the growth rate or rupture rate of asymptomatic AAAs. There may be some protective effects with ACE inhibitors, betablockers, and statins. – Beta-blockers can reduce cardiac morbidity and mortality and should be continued perioperatively. HR control and decreased contractility result in less systolic pressure generated against the aneurysm wall. – Statins’ pleiotropic effects have been shown to decrease postoperative cardiac, cerebral, and renal morbidity in patients undergoing major vascular surgery; should be continued perioperatively.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, CBC, BUN/CR, PT/PTT • 12-lead EKG • Echocardiography, stress testing, and coronary angiography may be indicated to evaluate the myocardium. • Carotid ultrasound if bruits are present, especially if history of stroke or TIA. • Ultrasound report should be reviewed even in patients presenting for nonvascular surgery. • CT scan with contrast or MRA is typically performed when patients present for repair; provides information on the position, diameter, and involvement of the mesenteric vessels. • Type and crossed units for open AAA repair

CONCOMITANT ORGAN DYSFUNCTION

• Aortic disease is indicative of other atherosclerotic diseases including coronary, cerebral, peripheral vascular, and renal diseases. • Chronic obstructive pulmonary disease • Diabetes mellitus

CIRCUMSTANCES TO DELAY/ CONDITIONS

• In patients presenting for nonvascular surgery, symptomatic and large aneurysms (i.e., >5.5 cm in diameter) as well as growth >1 cm/year should be considered for endovascular or surgical repair. • Acute coronary or cerebral event

CLASSIFICATIONS

• There are many classification systems in determining the risk of AAA rupture which take into account the rate of increase, size, comorbid factors, etc (2). • Biggest predictors of risk of rupture (annually) are diameter of the aneurysm and rate of expansion. – <4.0 cm in diameter = <0.5% – 4.0–4.9 cm in diameter = 0.5–5% – 5.0–5.9 cm in diameter = 3–15% – 6.0–6.9 cm in diameter = 10–20%

– 7.0–7.9 cm in diameter = 20–40% – >8.0 cm in diameter = 30–50%

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics as needed; anxiety may increase BP and the risk of AAA rupture. • Beta-blockers may be titrated to heart rate goals, particularly if taking chronically. • Perioperative statin therapy initiation may be indicated for their pleiotropic effects.

INTRAOPERATIVE CARE Choice of Anesthesia

• Non vascular procedures: Based on the type of surgery, patient comorbidities, and physical exam • Open AAA repair: Neuraxial techniques may be appropriate; however, traumatic placement may necessitate the delay of surgery (patients are heparizined intraoperatively). Monitors

• Standard ASA monitors • Non vascular procedures: Additional monitoring depends on the surgery and patient comorbidities. • Open AAA repair: – 2 large-bore peripheral IVs or a central introducer sheath for possible rapid fluid and blood administration – Arterial line to assess rapid hemodynamic changes and the potential for hypotension and MI; may be placed pre-induction. – Pulmonary artery catheter may be indicated when pulmonary vascular resistance, cardiac output, and mixed venous oxygen saturation can help guide therapy. – TEE may be indicated to evaluate myocardial function and detect regional wall motion abnormalities. Induction/Airway Management

• A slow, controlled induction is necessary to ensure an adequate depth of anesthesia and minimize hemodynamic changes. Hypotension can impair perfusion, while hypertension can result in aneurysmal rupture (transluminal pressures, coughing, bucking, etc.). • Short-acting agents, such as esmolol and nitroglycerin, may be necessary to blunt the patient’s response to tracheal intubation and the subsequent increased tension against the aneurysmal wall that could result in rupture. Maintenance

• Maintenance agents (non vascular and AAA repairs): Balanced volatile or intravenous techniques may be utilized. • Hemodynamics (non vascular and AAA repairs): Close titration of intravenous and

inhalation agents with an emphasis on reducing tension against the aneurysmal wall. Maintaining HR and MAP within 20% of baseline is generally appropriate (3). – Short-acting drugs permit a rapid termination of effect, if desired, and allow for enhanced titration. – Opioids, beta-blockers, and vasodilating drugs can be used to control pain and BP. Esmolol has ultra-short action and organ-independent elimination making it particularly useful. • Aggressive fluid replacement may cause dilutional and hypothermic coagulopathy. This can result in secondary clot disruption from increased blood flow, increased perfusion pressure, and decreased blood viscosity thereby exacerbating bleeding.

Extubation/Emergence

• Standard extubation criteria; special attention to blood loss, hemodynamics, and normothermia. Consider postoperative intubation in complicated AAA repairs or with significant comorbidities. • Smooth extubation (avoid coughing and bucking) • Control of hypertension and tachycardia is important; consider beta-blockers and/or vasodilators.

POSTOPERATIVE CARE BED ACUITY

• Non vascular repair: Depends on surgery, comorbidities, intraoperative course • AAA repair: ICU or monitored setting, given the high risk of cardiac complications. (MI occurs more frequently postoperatively than intraoperatively). The postoperative period is marked by increased myocardial oxygen demand, increased catecholamine levels, hypoxia, hypercoagulability, and large fluid shifts. Consider supplemental oxygen (nasal cannula, face mask), incentive spirometry and deep breathing, and early mobilization.

COMPLICATIONS

In AAA procedures, cardiac complications, such as myocardial ischemia or infarction are most commonly seen. Additionally, hemorrhage or coagulopathy, peripheral embolization, and aortocaval or aortoduodenal fistula can occur.

REFERENCES

1. Hatch C. Abdominal aortic aneurysm repair. In: Manual of anesthesia practice. Charlottesville, VA: Unbound Medicine, 2011. 2. Leonard A, Thompson J. Anaesthesia for ruptured abdominal aortic aneurysm. Contin Educ Anaesth Crit Care Pain. 2008;8(1):11–15. 3. CDC Aortic Aneurysm Factsheet. Available at: http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/docs/fs_aortic_aneurysm.pdf

ADDITIONAL READING

• Abdominal aortic aneurysm on UpToDate

• http://emedicine.medscape.com/article/463354-overview See Also (Topic, Algorithm, Electronic Media Element) • Thoracic aneurysm • Endovascular aneurysm repair • Abdominal aortic aneurysm, infrarenal • Abdominal aortic aneurysm, supraceliac

CODES ICD9

441.4 Abdominal aneurysm without mention of rupture ICD10 I71.4 Abdominal aortic aneurysm, without rupture

CLINICAL PEARLS

• Preoperative preparation should involve a careful assessment of the disease and comorbidities. • The US Preventive Services Task Force recommends screening for AAA using ultrasound imaging one-time for men aged 65–75 years who have ever smoked, even if they have no symptoms. Men aged ≥60 years with a family history of AAA may also be tested.

ABDOMINAL AORTIC ANEURYSM RUPTURE John W. Hoffman, Jr., DO, MS Shawn T. Beaman, MD

BASICS DESCRIPTION

• The abdomen is the most common site for an aortic aneurysm. – Abdominal aortic aneurysms (AAA) are most commonly located between the inferior mesenteric and renal arteries. – Approximately two-thirds of all AAAs extend into the iliac arteries • Ruptured AAA (rAAA) is a surgical emergency.

EPIDEMIOLOGY Incidence

• AAA is present in 5–10% of patients >65 years old (1)[C]. • Estimated to occur in 7.7 to 26.8 per 100,000 person-years in recent large European study (remarkable variation was noted across countries). Morbidity

• Respiratory insufficiency (5–10%) • Myocardial infarction (10–15%) • Renal insufficiency (2–5%) • GI complications (3–4%) • Lower extremity ischemia (2–5%)

Mortality

• rAAA is the 13th leading cause of death in the US, with up to 15,000 deaths annually. • 30–50% of patients with a rAAA do not survive transport to a hospital. • Operative mortality after rupture ∼ 50%

ETIOLOGY/RISK FACTORS

• Risk factors associated with AAA rupture (6)[C]: – Anteroposterior aneurysm diameter >5 cm – Elevated diastolic pressure – Obstructive pulmonary disease • Causes of AAA: – Atherosclerosis (most common) (2–5)[C] – Connective tissue diseases (e.g., Marfan syndrome, Ehlers–Danlos syndrome, and cystic medial necrosis) (2)[C] – Infectious etiologies are uncommon (e.g., syphilis, salmonellosis, brucellosis, tuberculosis) (2)[C].

• Risk factors associated with presence of AAA: – Smoking: Duration (years) of tobacco exposure is more important than absolute number of cigarettes (2)[C]. – Age >65 years old – Male gender: Incidence is 4 times higher in men; women have delayed development of AAA by ∼10 years compared with men. – Hypertension – Presence of peripheral arterial aneurysms (e.g., popliteal or femoral arterial aneurysm) – Family history of AAA (first-degree relative) – Decreased serum high-density lipoprotein – Caucasian ethnicity PATHOPHYSIOLOGY

• Collagen and elastin fibers provide most of the tensile strength of the aortic wall. An imbalance between aortic wall matrix metalloproteinases and their inhibitors, chronic inflammatory infiltrates, smooth muscle apoptosis, and increased production of proinflammatory cytokines contribute to aneurysm formation. • The average rate of growth of a AAA is 0.4 cm/year • Risk of rupture is proportional to wall stress/tension, which increases as the AAA expands (Laplace’s law).

ANESTHETIC GOALS/GUIDING PRINCIPLES • Intravascular volume replacement • Inotropic support of cardiac output • Maintenance of adequate tissue oxygenation • Immediate surgical control of rupture

PREOPERATIVE ASSESSMENT SYMPTOMS

Back, chest, or abdominal pain History

• Comorbidities are common. – Atherosclerosis associated with coronary artery disease, stroke, peripheral vascular disease, and renal insufficiency – Smoking associated with obstructive pulmonary disease • Presence of connective tissue disease • Medical optimization is not feasible due to the emergent nature of the surgery.

Signs/Physical Exam

• Pulsatile abdominal mass • Hypotension

TREATMENT HISTORY

Pre-existing vascular grafts or repairs MEDICATIONS

• Vasodilators (nitroglycerin and/or nitroprusside) • Short acting beta blockers (e.g. esmolol) are utilized to decrease the heart rate.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Baseline and serial cardiac biomarkers, BUN/Cr, CBC with platelets, coagulation profile, and TEG if available • ECG may be normal or show nonspecific ST segment or T wave changes, left ventricular hypertrophy, ischemia, or infarction. • Chest radiograph may suggest concomitant pulmonary disease. • CT angiography is quick, highly sensitive, and specific; 64-slice multidetector CT with cardiac gating may allow for simultaneous evaluation of pulmonary and coronary arteries. • TEE allows rapid evaluation of cardiac function, volume status, and valvular integrity. • MRI/MRA has high sensitivity and specificity, avoids radiation, and iodinated contrast; but is more time-consuming and contraindicated with metallic implants. CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular: Coronary artery disease (30–40%), hypertension, peripheral vascular disease • Neurologic: Cerebrovascular disease • Pulmonary: Chronic obstructive pulmonary disease (COPD), smoking history • Renal: Chronic renal insufficiency • Endocrine: Diabetes mellitus

CIRCUMSTANCES TO DELAY/ CONDITIONS

None; rAAA has a mortality that exceeds 80% if not repaired. CLASSIFICATIONS

• Anterior intraperitoneal rupture (20%): Rapid bleeding into the peritoneal cavity usually results in exsanguination and death before the patient arrives at the hospital (1)[C]. • Retroperitoneal rupture (80%): Tamponade effect limits internal hemorrhage. Associated with a lower mortality rate (1)[C].

TREATMENT PREOPERATIVE PREPARATION Premedications

• Analgesia: Small incremental doses of opioids • Sedation: Avoid in hemodynamically unstable patients • Bronchodilators: Symptomatic patients with COPD • Antihypertensive/anti-anginal: Continued until time of surgery if hemodynamically stable • Blood products: pRBCs, platelets, FFP, cryoprecipitate

Special Concerns for Informed Consent • May not be possible in emergency • Blood consent

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia • Continuous epidural anesthesia may be considered if rupture is contained and coagulation status is normal. However, placement should not occur in hemodynamically unstable patients or if it will delay surgery.

Monitors

• ECG with ST-segment analysis • Arterial line: Pre-induction placement in radial artery is commonly performed. Femoral artery insertion may permit monitoring of distal perfusion pressures. • Central venous access is appropriate for monitoring pressures and administration of vasoactive medications. • TEE facilitates continuous evaluation of intravascular volume, valvular integrity, and ventricular function. • Pulmonary artery catheterization provides SvO2, SVR, CO, PAP. • Temperature (central and peripheral sites if bypass is to be used) • Foley catheter • Cell salvage, rapid infuser

Induction/Airway Management

• Slow, controlled titration of induction medications: In patients at risk for pulmonary aspiration, the decision to proceed with an RSI should be balanced against the potential for hypertension. – Control of hypertensive response to laryngoscopy and intubation can be accomplished with moderate-dose narcotics. – Avoid hypotension which may contribute to cardiac ischemia and further deterioration of peripheral perfusion. • Single-lumen endotracheal tube is sufficient for surgery contained to the abdominal cavity. Lung isolation with a double-lumen tube or bronchial blocker is preferred for procedures extending into the thorax. • Positive pressure ventilation may decrease venous return and further decrease cardiac output and peripheral perfusion.

Maintenance

• Position: Supine with transperitoneal approach; the lateral decubitus position and retroperitoneal approach may be preferred in certain situations. • Thermoregulation: Forced air and fluid warming systems are necessary due to significant heat loss with open procedures. • Fluid management: Maintenance of intravascular volume may be challenging due to

significant hemorrhage and evaporative losses; no specific colloid or crystalloid strategy has emerged as superior. • Coagulation: Consumption and dilution of coagulation factors and platelets may be significant; replacement is guided by conventional coagulation studies as well as TEG, if available. • Renal protection: Maintenance of renal blood flow and urine output is essential. IV sodium bicarbonate, mannitol, and fenoldapam may decrease the risk of kidney injury (mannitol and fenoldapam should not be used in hemodynamically unstable patients). • Placement of aortic cross-clamp – Increase in left ventricle (LV) afterload and potential for cardiac collapse. Acute increases in systemic vascular resistance (SVR) can be mitigated with vasodilators (nitroprusside, nitroglycerin, calcium channel blockers, propofol). – Decrease in venous return: Gentle administration of IV fluids may augment preload. – Suprarenal clamping decreases renal perfusion. Consider administration of mannitol (0.25–0.5 g/kg) prior to clamping. • Removal of aortic cross-clamp – Release of vasoactive metabolites into the central circulation can lead to hypotension and cardiac arrhythmias. – Decreases in the SVR are mitigated with IV fluids and vasopressors (phenylephrine or epinephrine). Profound, unresponsive hypotension can be temporarily treated with reinstigation of the aortic clamp.

Extubation/Emergence

• Ongoing cardiac or pulmonary instability, bleeding, hypothermia, or neurologic injury may necessitate continued mechanical ventilation; otherwise patients may be extubated at the conclusion of the procedure. • Pain, hypertension, and tachycardia should be anticipated and addressed.

POSTOPERATIVE CARE BED ACUITY

• Intensive care unit • Monitoring of BP, HR, and LV function • Analgesia with intravascular or neuraxial opioids • Continued assessment of graft patency and peripheral perfusion

COMPLICATIONS

• Hemorrhage • Coagulopathy • Myocardial ischemia/infarction • Renal failure • Incision and/or graft infection • Spinal cord ischemia, paralysis • Impotence • Bowel ischemia

• Embolism • Lower extremity ischemia • Pneumonia, respiratory insufficiency • Hypothermia

REFERENCES

1. Assar A, Zairians C. Ruptured abdominal aortic aneurysm: A surgical emergency with many clinical presentations. Postgrad Med J. 2009;85:268–273.

2. rattheim BJ, Elkemo TA, Altreuther M, et al. Regional disparities in incidence, handling and outcome of patients with symptomatic ruptured abdominal aortic aneurysms in Norway. Eur J Endovasc Surg. 2012.

3. ozniak F, LaMuraglia GM, Musch G, et al. Anesthesia for open abdominal surgery. Int Anesth Clin. 2005;43(1):61–78. 4. Thompson R, Geaghty P, Lee J. Abdominal aortic aneurysms: Basic mechanisms and clinical implications. Curr Probl Surg. 2002;39:110–130. 5. Adam van der Vliet J, Boll A. Abdominal aortic aneurysms. Lancet. 1997;349:863–866. 6. Bernstein E, Chan E. Abdominal aortic aneurysm in high risk patients: Outcome of selective management based on size and expansion rate. Ann Surg. 1984;200(3):255–263. 7. Falk J, Rackow EC, Blumenberg R, et al. Hemodynamic and metabolic effects of abdominal aortic cross-clamping. Am J Surg. 1981;142:174–177. 8. Subramaniam B, Singh N, Roscher C, et al. Innovations in treating aortic diseases: The abdominal aorta. J Cardiothorac Vasc Anesth. 2011 (article in press). 9. Gelman S. The pathophysiology of aortic cross clamping and unclamping. Anesthesiology. 1995;82(4):1026–1060.

See Also (Topic, Algorithm, Electronic Media Element) • Abdominal aortic aneurysm • Abdominal aortic aneurysm dissection

CODES ICD9 441.3 Abdominal aneurysm, ruptured ICD10 I71.3 Abdominal aortic aneurysm, ruptured

CLINICAL PEARLS

• rAAA is a surgical emergency. Mortality exceeds 80% without intervention; with repair it can decrease to ~50%. • Patients often present with significant cardiac, cerebral, and/or renal vascular disease.

• Application of the aortic cross-clamp leads to an abrupt increase in afterload and may precipitate cardiac collapse. • Removal of the aortic cross-clamp causes a decrease in SVR and release of vasoactive metabolites into the central circulation.

ABDOMINOPERINEAL RESECTION (APR) Vijaya Gottumukkala, MB, BS, MD, FRCA

BASICS DESCRIPTION General

• Ernest Miles (1869–1947) devised the approach in the 1930s as a curative procedure for all rectal cancers. It involves resection of the anus, rectum, and a portion of the sigmoid colon, as well as a wide perineal and lymph node dissection. • Abdominoperineal resection (APR) is now reserved for conditions where the rectum needs to be removed and there is involvement of the primary sphincter complex or tumors in the lower third of the rectum that do not have adequate clearance for sphincter preservation. It requires a permanent colostomy. • Laparoscopy-assisted APR and low anterior resection (LAR) are more commonly performed today. LAR is a modified technique that allows for sphincter preservation. Position

• Modified lithotomy • Trendelenburg, as needed

Incision

Midline abdominal and perineal Approximate Time 5–10 hours

EBL Expected

500–1,500 mL Hospital Stay 7–10 days

Special Equipment for Surgery

• 2 table set-up (abdominal and pelvic sets) • Long pelvic instruments, stapling devices • Cystoscopy set with ureteric stents

EPIDEMIOLOGY Incidence

• Colorectal cancer is the 4th most common cancer and the second leading cause (10%) of all cancer-related deaths.

• From 2003 to 2007, the median age at diagnosis for colorectal cancer was 70 years of age. At diagnosis, about 20% had distant metastasis. • 5–10% of all colorectal cancers are associated with a familial colorectal cancer syndrome, and an additional 15–20% are associated with a familial disposition. • Risk for colorectal cancer increases with age (90% of cases occur in patients >50 years), and with a diet rich in red meat and animal fat. • Aspirin, NSAIDs, and COX-2 inhibitors have been reported to have protective effects against colorectal cancer.

Prevalence

• As of January 1, 2007, in the US there were approximately 1,112,493 men and women alive with a history of colon and/or rectal cancer. • Based on rates from 2005 to 2007, 5.12% of men and women born today will be diagnosed with cancer of the colon and/or rectum during their lifetime. • High incidence of local recurrence despite margin-free resection

Mortality

• The overall 5-year relative survival in the US for 1999–2006 was 65.0%; for high-risk patients it is 20%. • Hormone replacement therapy has been shown to significantly reduce mortality in women with colorectal cancer.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patient population with sequelae related to the primary pathology and significant medical comorbidities (age, smoking, diabetes, hypertension, atherosclerosis, coronary artery disease, malnutrition). Optimize preoperative comorbid burden for optimal postoperative recovery. • Maintenance of tissue oxygenation, perfusion, and euvolemia. Patients are often placed on a clear liquid diet 1–3 days prior to surgery, combined with bowel prep (laxative, enemas, whole gut irrigation with saline via a nasogastric tube, polyethylene glycol electrolyte lavage, or mannitol solution). • Effective analgesia (epidural preferred for open procedures) • Extubation at the end of surgery • Postoperative monitoring in a high-dependency unit for 48 hours

PREOPERATIVE ASSESSMENT SYMPTOMS

• Symptomatic, depending on the size and location of the tumor • Change in bowel habits and pencil stools • Rectal or lower abdominal pain, spotting of blood in stool, lower GI bleeding, hematochezia, and tenesmus • May be acutely or chronically ill depending on the primary pathology (Crohns disease, ulcerative colitis)

History

• Inflammatory bowel diseases (Crohns disease, ulcerative colitis), inherited colon cancers (familial adenomatous polyposis, Gardner syndrome, Peutz–Jeghers syndrome, juvenile polyposis, and hereditary non-polyposis colon cancer) • Careful assessment of the sequelae and complications of the primary colonic/rectal pathology, medical comorbidities, nutritional and functional status Signs/Physical Exam

• Systemic signs of inflammatory bowel disease (IBD) • Anemia, weight loss, fever of unknown origin • Abdominal wall and/or internal colonic fistulae • Palpable mass in the recto-sigmoid on examination

MEDICATIONS •

Therapy for IBD: Antidiarrheals, aminosalicylates (5-ASA), corticosteroids, immunomodulators (azathioprine and 6-mercaptopurine, cyclosporine), antibiotics, and pain medications • Patient may have recently completed adjuvant chemoradiation prior to surgery and/or planned for after surgery. • Chemotherapy for colorectal cancer is 5-FU and leucovorin based. Irinotecan or oxaliplatin is added in metastatic disease. • Medications for the comorbidities (antihyperglycemics, antihypertensives, anticholesterol medications, aspirin, etc.) DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC, PT/PTT, creatinine, prealbumin, and LFTs • Electrolytes if on diuretics, ACE I, renal insufficiency • Colonoscopic evaluation (location, size, and number of masses) • CT scan (tumor location, size, perirectal and vascular involvement, peritoneal and liver metastasis) • Other tests (TEG, ECG, CXR, cardiac echocardiogram, exercise stress test, PFTs) as indicated

CONCOMITANT ORGAN DYSFUNCTION

• Anemia from bleeding or occult blood loss • Metastasis: Abdominal pain (hepatomegaly) and liver dysfunction from hepatic metastasis; skeletal pain from bony metastasis; ascites from peritoneal dissemination; bladder dysfunction, sacral or sciatic neuropathy, and vaginal discharge and bleeding from pelvic metastasis • Obesity/malnutrition • Inflammatory bowel disease and its associated sequelae • Age-related morbidities: Diabetes, hypertension, coronary artery disease

TREATMENT

PREOPERATIVE PREPARATION Premedications

• Anxiolytic and analgesic medications, as needed • Gastric volume reducing and acid-neutralizing medications, if indicated • Continue appropriate medications (antibiotics, anti-inflammatory/immunomodulators, antihypertensives, antiarrhythmics, and others) as needed • There is an increasing trend to use alvimopan to hasten recovery of bowel function.

Special Concerns for Informed Consent

• Blood consent for possible transfusion • Consent for epidural catheter for postoperative analgesia • Potential for postoperative intubation and intensive care

Antibiotics/Common Organisms

• Prophylactic cefotetan or cefoxitin; metronidazole plus an aminoglycoside may be used for cephalosporin allergy. • Gram-negative aerobes and anaerobic bacteria • Mechanical bowel preparation decreases fecal bulk, but does not decrease the concentration of bacteria in the stool.

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with ETT • Epidural catheter for postoperative analgesia: Need to rule out contraindications, review medication list (herbals, clopidogrel, low-molecular-weight heparin, or other drugs that alter coagulation), consider preoperative PT/PTT/INR or other advanced coagulation tests as needed (TEG, PFA). Not contraindicated with usual thromboprophylaxis for postoperative DVT (heparin 5,000 U SQ BID).

Monitors

• ASA standard monitors • Arterial line (beat-to-beat blood pressure monitoring, systolic pressure variation [SPV] to evaluate intravascular volume status, blood draws for lab work); consider placing the arterial line pre-induction for high-risk patients. • 2 large-bore IVs for volume resuscitation if needed. Central line access is not usually necessary unless there is poor IV access or a need for postoperative TPN. • Foley catheter: Ureteric stents are placed preoperatively to identify ureters during the resection.

Induction/Airway Management

Standard induction technique and strategies to maintain hemodynamic stability and full stomach precautions if indicated Maintenance

• Avoid nitrous oxide. Air–oxygen mixture with an FiO2 of 0.5 will help identify oxygenation

issues early. • Continuous epidural infusion of local anesthetic/narcotic mixture may be used for analgesia throughout the procedure. • Nasogastric tube placement may be requested. • Volume: APR is a major procedure with complex bowel resection; bleeding may be encountered from the presacral venous plexus. Additionally, insensible fluid losses can result. Intravascular volume status and maintenance of organ perfusion should be closely monitored. • Surgeon may request intraoperative indigo carmine to rule out injury to the ureters; it may temporarily result in a decrease in the pulse oximeter reading. • Blood glucose, serum electrolytes, ABG, ACT and other coagulation parameters as may be checked needed. Extubation/Emergence

• Standard extubation criteria • Post-extubation sensory–motor exam and evaluation of epidural puncture site for effectiveness and complications

POSTOPERATIVE CARE BED ACUITY

• High-dependency unit or ICU for 48 hours • May need monitoring of invasive hemodynamic parameters to guide fluid volume/blood product transfusion ANALGESIA

• Epidural: Follow ASRA guidelines for maintenance and removal of epidural catheters • Multimodal approach involving IV PCA if epidural contraindicated or laparoscopic procedure COMPLICATIONS

• Intra-abdominal abscess, wound infections (10%), anastomotic leaks (15%) • Postoperative ileus • Injury to the ureters, hypogastric or parasacral nerve plexus • Postoperative fever and leukocytosis are not uncommon. • Adverse cardiac events (hypotension, hypertension, arrhythmias, ischemia, infarct, and CHF) • Postoperative delirium in elderly • Postoperative neuropathies from positioning • Epidural site infection or hematoma (very rare)

PROGNOSIS

• Overall local recurrence is 30% after a margin-free resection. • The best prognosis in patients with locally advanced rectal cancer appears to be after preoperative chemoradiation, maximal surgical resection (margin free), and localized

intraoperative radiation therapy (IORT) in selected cases.

REFERENCES

1. Ferg BW, Berger DH, Fuhrman GM. Cancer of the colon, rectum and anus. In: Chang G, Feig BW. The M.D. Anderson surgical oncology handbook, 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2006:261. 2. Lindholm ML, Träff S, Granath F, et al. Mortality within 2 years after surgery in relation to low intraoperative bispectral index values and preexisting malignant disease. Anesthes Analges. 2009;108(2):508–512.

3. Green D, Paklet L. Latest developments in the peri-operative monitoring of the high risk surgical patient. Int J Surg. 2010;8(2):90–99. 4. Kimberger O, Arnberger M, Brandt S, et al. Goal-directed colloid administration improves the microcirculation of healthy and perianastomotic colon. Anesthesiology. 2009;110(3):496–504.

ADDITIONAL READING

• Cancer Facts and Figures 2010. Atlanta, GA: American Cancer Society, 2010. • Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute

See Also (Topic, Algorithm, Electronic Media Element) • Insensible fluid losses • International normalized ratio • Partial thromboplastin time • Prothrombin time

CLINICAL PEARLS

• Major bowel resection surgery can require significant blood products and fluid resuscitation in the perioperative period. • There exists a risk for positioning and surgery-related neuropathies. • Patients are prone to the occurrence of late DVTs.

ACE INHIBITORS AND HYPOTENSION John B. Carter, MD

BASICS DESCRIPTION

• Significant hypotension has been reported after the induction of general anesthesia in patients on angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs). • At this time, guidelines have not been established regarding preoperative management (withdrawal or continuation) of ACEI or ARBs. Large randomized controlled studies are lacking and most information stems from retrospective studies: – Elective, noncardiac surgical patients who have taken ACEI or ARBs on the morning of surgery appear to have an increased risk of moderate hypotension (systolic blood pressure [SBP] <85 mm Hg) (1) and vasopressor requirement (2). – Vascular surgical patients who have taken ACEI or ARBs on the morning of surgery appear to have an increased incidence of hypotension and level of severity (3). – Cardiac surgical patients who withhold ACE inhibitors before surgery appear to maintain a greater MAP and require less vasopressors while on bypass. Additionally, they may require more vasodilator therapy post-bypass and do not incur hypotension at the time of anesthesia induction (4). EPIDEMIOLOGY Incidence

• ACEI/ARBs are frequently prescribed for antihypertensive therapy with particular advantages in: – Renal protection in diabetes mellitus (DM) and hypertension (HTN) – Prevention of cardiac remodeling after myocardial infarction (MI) • Lower risk of cerebrovascular accident (CVA) and MI (4)

Prevalence

Approximately 50 million individuals in the US (and 1 billion worldwide) have HTN. Morbidity

In addition to causing hypotension, ACEI/ARBs can also cause renal impairment and hyperkalemia. They are contraindicated in renal artery stenosis and should be used with caution in hypovolemia. ETIOLOGY/RISK FACTORS

Concurrent use of diuretics with ACEI/ARBs has been associated with a higher risk of hypotension during anesthesia (2). PHYSIOLOGY/PATHOPHYSIOLOGY

• The physiology of the renin-angiotensin-aldosterone system (RAAS) plays an essential role in the short-term regulation of blood pressure and long-term regulation of intravascular volume. – Angiotensinogen is an inactive glycoprotein produced in the liver. – Renin is secreted by the kidneys into the bloodstream when pressure receptors sense low blood volume. Renin is highly specific in cleaving angiotensinogen to angiotensin I. – Angiotensin converting enzyme (ACE) is a nonspecific enzyme in the vascular endothelium which converts angiotensin I to angiotensin II. ACE also inactivates bradykinin, a potent vasodilator. – Angiotensin II can cause immediate vasoconstriction of arterial and venous vessels, with a resultant increase in the systemic vascular resistance (SVR) and venous return. It constricts renal efferent arterioles during moderate decreases in perfusion pressure in order to preserve the glomerular filtration rate (GFR). Small amounts are also produced independently of ACE. – Aldosterone is produced by the adrenal glands in response to angiotensin II and hyperkalemia. It plays a role in sodium retention and increasing the blood volume; it has a slower response and longer duration (5). • Blood pressure regulation is also maintained by other systems. – The sympathetic nervous system maintains vascular tone, heart rate, and contractility; however, induction of anesthesia results in a reduction of sympathetic tone in both the arterial and venous vessels. This results in a lower SVR as well as decreases in effective blood volume and preload. – Vasopressin (antidiuretic hormone) is an important compensatory mechanism in hypovolemia. • Refractory hypotension: ACEI and ARBs impair the RAAS; general anesthesia impairs the sympathetic nervous system. Thus, the combination leaves the vasopressin system as the main mechanism of maintaining blood pressure. • Other: – Genetics may influence which patients are susceptible to hypotension following induction. – Neuraxial blocks: Whether ACEI or ARBs cause refractory hypotension in patients receiving an epidural or spinal is unclear.

PREVENTATIVE MEASURES

• Patients may be asked to withhold their ACEI/ARB on the day of surgery. • If they are not withheld, cancellation of surgery is not necessarily warranted. Consider volume administration, the use of an induction agent other than propofol (or lower doses), and having vasopressors including vasopressin available.

DIAGNOSIS Despite intraoperative hypotension being an independent predictor of mortality in the first year after surgery (12), no standard definition exists. • A common practical approach is to establish the patient’s baseline from several readings and attempt to stay within 20% (6).

• However, the lowest “safe” blood pressure will vary with an individual’s comorbidities such as aortic stenosis or cerebrovascular insufficiency. • Adequate cerebral perfusion has been cited as a MAP >70 mm Hg (7), with higher MAPs often necessary in chronic HTN. MAPs <70 mm Hg may be tolerated for a short time in hypertensive patients. Cerebral ischemia resulting in stroke was not noted in these studies.

DIFFERENTIAL DIAGNOSIS

Hypotension, in general, may be seen in ∼9% of patients in the first 10 minutes following the induction of anesthesia (8). The following predictors were found: • ASA III-V • Age >50 • Baseline MAP <70 mm Hg • Use of propofol for induction • Increased doses of fentanyl • Chronic HTN • Hypovolemia

TREATMENT • Volume infusion • Sympathomimetics such as ephedrine or phenylephrine as first-line treatment. One study showed that doses of ephedrine and phenylephrine did not usually exceed 20–25 mg and 200 mcg, respectively (3). • Vasopressin may be helpful in refractory cases. It is usually administered as an infusion for vasodilatory shock; bolus therapy is off label. It may have a more sustained effect than other pressors. • Terlipressin, an AVP analog, may also be useful (9). • Methylene blue has been reported in the treatment of refractory hypotension. The mechanism of action is an in inhibition of cGMP in the endothelium.

REFERENCES

1. Comfere T, Spring J, Kumar M, et al. Angiotensin system inhibitors in a general surgical population. Anesth Analg. 2005;100:636–644. 2. Pigott DW, Nagle C, Allman K, et al. Effect of omitting regular ACE inhibitor medication before cardiac surgery on haemodynamic variables and vasoactive drug requirement. Br J Anesth. 1999;83:715–720. 3. Bertrand M, Gilles G, Meersschaert K, et al. Should the angiotensin II antagonists be discontinued before surgery. Anesth Analg. 2001;92:26–30. 4. White W. Angiotensin-converting enzyme inhibitors in the treatment of hypertension: An update. J Clin Hypertens. 2007;9:876–882. 5. Colson P, Ryckwaert F, Coriat P. Renin angiotensin system antagonists and anesthesia. Anesth Analg. 1999;89:1143–1155.

6. Howell SJ, Sear JW, Foex P. Hypertension, hypertensive heart disease, and perioperative cardiac risk. Br J Anaesth. 2004;92:570–583. 7. Drummond JC. The lower limit of autoregulation: Time to revise our thinking? Anesthesiology. 1997;86:1431–1433.

8. Reich D, Hossain S, Baez B, et al. Predictors of hypotension after induction of general anesthesia. Anesth Analg. 2005;101:622–628.

9. Meersschaert K, Brun L, Gourdin M, et al. Terlipressin-ephedrine versus ephedrine to treat hypotension at the induction of anesthesia in patients chronically treated with angiotensin converting-enzyme inhibitors: A prospective, randomized, double-blinded, crossover study. Anesth Analg. 2002;94:835–840. 10. Hohne C, Meier L, Boemke W, et al. ACE inhibition does not exaggerate the blood pressure decrease in the early phase of spinal anaesthesia. Acta Anaesthesiol Scand. 2003;47:891–896. 11. heterpal S, Khodaparast O, Shanks A, et al. Chronic angiotensin-converting enzyme inhibitor or angiotension receptor blocker therapy combined with diuretic therapy as associated with increased episodes of hypotension in noncardiac surgery. J Cardiothoracic Vasc Anesth. 2008;22:180–186. 12. Monk TG, Saini V, Weldon BC. Anesthetic management and one-year mortality after noncardiac surgery. Anes Analg. 2005;100:4–10.

ADDITIONAL READING

• Augoustides J. Angiotensin blockade and general anesthesia: So little known, so far to go. J Cardiothoracic Vasc Anesth. 2008;22:177–179. • Smith I, Jackson I. Beta-blockers, calcium channel blockers, angiotensin receptor blockers: Should they be stopped or not before ambulatory anaesthesia. Curr Opin Anesth. 2010;23:687–690.

See Also (Topic, Algorithm, Electronic Media Element) • Angiotensin • Hypotension • Renin

CODES ICD9 458.8 Other specified hypotension ICD10 I95.2 Hypotension due to drugs

CLINICAL PEARLS

• Hypertensive patients often demonstrate very labile blood pressures. Excessive drops in MAP cause concern for a possible increase in morbidity and possibly mortality. • Following induction of anesthesia in association with use of ACEI/ARBs, there appears to be an increased incidence of hypotension due to a reduction in vascular tone, especially on the venous return. The angiotensin II system is unable to compensate for the hypotension; therefore, these patients are more volume sensitive to maintain preload. • Arguments against discontinuing ARBs and ACEI include: Neuroprotection, as well as improved hemodynamic stability, decreased ischemia–reperfusion injury, and renal protection.

ACLS ANESTHETIC MANAGEMENT Mark E. Nunnally, MD, FCCM

BASICS DESCRIPTION

• The American Heart Association’s Advanced Cardiac Life Support (ACLS) course is evidencebased consensus products to assist practitioners with emergency scenarios, in particular cardiac arrest. They are intentionally broad in scope (1). • Algorithms treat distinguishable syndromes to specify care. These are often cardiac rhythm based (e.g., asystole vs. ventricular tachycardia). • ACLS guidelines, however, may not fit the most common arrest scenarios seen in the operating room (OR). – ACLS treats probabilities; these are not specific to the surgical setting. – There is no provision in ACLS for a previously ventilated patient. – Arrest in the OR is witnessed, usually evolves over minutes, and can be treated with a broad range of resources. EPIDEMIOLOGY Incidence

• Data for arrest or near arrest in the OR are difficult to assess. Best estimates are 4.3–19.7 cardiac arrests per 10,000 anesthetics for adults (approximately 10% of these are directly attributed to anesthesia) and 2.6–11 per 10,000 for children (much higher in infants) (2,4). • Arrest during neuraxial anesthesia is estimated at 1.8 per 10,000 anesthetics and is more common with spinal anesthesia than epidural anesthesia (4). • Most available data on intraoperative cardiac arrest come from registries or closed-claims databases. These are useful tools for studying rare events but cannot be trusted for accurate incidence data. Prevalence

• Arrest is an incident phenomenon, but there are many prevalent factors in the OR that influence the risk and type of arrest. – Intraoperative hypovolemia is common and an important cause of shock. – Patient comorbidities contributing to arrest include cardiac and thromboembolic disease. – Anesthetic agents are potent and their overdose accounts for the majority of arrests attributable to anesthesia. Induction drugs and volatile anesthetic agents are potent vasodilators and negative inotropes. – Arrest at induction has declined while arrest during maintenance or emergence has remained the same. Esophageal intubation and airway loss are less common since the use of capnography and pulse oximetry became routine (8). – Complications of intravascular access (e.g., hemorrhage, pneumothorax, tamponade) are rare but serious causes.

• The frequency of arrhythmias under anesthesia is different. The most common arrhythmias include (7): – Bradycardia followed by asystole (45%) – Unknown (33%) – Ventricular tachycardia/ventricular fibrillation (14%) – Pulse-less electrical activity (7%)

Morbidity

• Hypoxic neurologic injury is the salient morbidity of cardiac arrest. It is a prominent factor in closed-claims data, associated with some of the highest payments. • Pancreatitis, hepatic dysfunction, renal failure, and the multiple organ dysfunction syndrome (MODS) can follow prolonged shock after cardiac arrest.

Mortality

• Estimated mortality from an intraoperative arrest ranges from 20% to 50%, compared with 84–97% for out-of-hospital cardiac arrest (US data) (5). • In one large series from the Mayo Clinic, in-hospital mortality was 21% from arrests directly attributable to anesthesia, versus 71% in those that were not. Other smaller series suggest higher mortality in anesthesia-attributable arrest (up to 80%) (6). • Factors associated with mortality include: ASA patient status, emergency surgery, diabetes mellitus, end-stage organ failure, protracted hypotension or use of vasopressors prior to arrest, invasive monitoring, and type of surgery (cardiac surgery worst). • Unlike other patient populations, asystole is associated with good survival (80% in one series), suggesting it is mediated by autonomic or drug effects, and is therefore reversible in many cases. • Mortality differences suggest that the combination of different etiologies, witnessed arrest, and timely availability of advanced resuscitation techniques make intraoperative arrest different from community arrest.

ETIOLOGY/RISK FACTORS

• Arrest in the OR is multifactorial. • Ischemic heart disease and conduction abnormalities share etiologies with causes of arrest outside the OR. • Patient comorbidities are the most likely contributors to cardiac arrest, followed by surgical and anesthetic factors. • Anaesthetists cannot prepare for every emergency the same way. Training in arrest management should target 4 specific cause groups: – Events specific to anesthetic intervention (e.g., pneumothorax, high spinal) – Reactions to specific agents (e.g., local anesthetic systemic toxicity, malignant hyperthermia) – Factors that occur more frequently, even though they do not always cause arrest, such as hypovolemic shock and hypoxemia – Relatively “common” rare causes (somewhere between 0.1 and 1 in 10,000 anesthetics) • Some causes of arrest in the OR that result from direct intervention include: – Hypoxemia

– Hemorrhage – Vagal stimulation – Emboli (e.g., venous air embolism) – Over-ventilation/auto-PEEP – Drug reactions (anaphylaxis, malignant hyperpyrexia)

PHYSIOLOGY/PATHOPHYSIOLOGY

• Since arrest data come from retrospective sources, only correlation can be ascertained. Causation must be speculative. – Preload (hemorrhage, capillary leak, hypovolemia) – Afterload (vasoplegia, drug effect) – Pump function (right heart, left heart, contractility, dysrhythmia) – Impaired filling (tamponade, auto-PEEP, abdominal compartment syndrome) • Retrospective evaluation of arrests suggests a correlation with preclinical signs. – Hypotension – Tachycardia – Abrupt drops in end-tidal CO2 are particularly ominous. PREVENTATIVE MEASURES

• MOST of what anaesthetists do involves avoiding arrest scenarios. Skilled anaesthetists proactively avoid disaster before signs of deterioration become apparent. • The time between a problem becoming detectable and arrest can be short as problems escalate. • Rapid treatment is most likely to improve outcomes.

DIAGNOSIS • Disaster evolves quickly; thus, diagnosis and rescue treatment should occur simultaneously. • Monitor failures are far more common than arrest, but must be addressed quickly and arrest scenarios should always be ruled out first. • Factors associated with arrest include: – Change in ECG to pulse-less rhythm – Loss of palpable pulse or arterial waveform pulsatility – Loss of end-tidal CO2 (very specific, values <10 mm Hg are associated with severe loss of cardiac output and the need for chest compressions). – Loss of plethysmograph waveform • Do not spend more than 10 seconds seeking a pulse before beginning chest compressions. Return of spontaneous circulation (ROSC) is associated with preserved myocardial oxygen tension, which depletes rapidly without CPR. • Screening for specific risks helps identify sources of arrest (e.g., history of allergy/adverse drug reactions, obstructive airway disease, aortic stenosis, prolonged QT syndrome). • Pulse pressure variation >15%, with a tidal volume of 8–10 mL/kg, predicts fluid responsiveness. In a population at high risk for hypovolemia, this can be very useful. • If available, a focused, rescue transesophageal echocardiography can aid with diagnosis

(comparative chamber size, wall motion abnormalities, and signs of embolic phenomena). • Chest radiography may aid with ruling out probable complications of central venous cannulation (e.g., hemorrhage, pneumothorax).

DIFFERENTIAL DIAGNOSIS

• Pathophysiologic mechanisms are a useful way to organize etiologies and treatments. • Anesthetic causes: Drug overdose, high neuraxial block, local anesthetic systemic toxicity, malignant hyperthermia, drug swap, anaphylactic reaction • Respiratory causes: Hypoxemia, auto-PEEP, hypoxemia, bronchospasm, tension pneumothorax • Cardiovascular causes: Hemorrhage, hypovolemia, acute coronary syndrome, pulmonary hypertension, right heart failure, pulmonary embolism (thrombus, air, fat, etc.), long QT syndrome (Torsades de Pointes), pacemaker failure, oculocardiac syndrome, tamponade, increased intra-abdominal pressure, inferior vena cava (IVC) compression (e.g., flex position, gravid uterus) • Metabolic causes: Electrolyte imbalance (hyperkalemia), transfusion reaction

TREATMENT • CPR should be initiated quickly (allow no more than 10 seconds to find a pulse in suspected arrest) [C]. • Compression rate should be 100/minute and each compression should be at last 51 mm in depth (1). • Respiratory rate should be no more than 10 breaths/minute (1). • Local anesthetic systemic toxicity: Intralipid™ rescue is associate with ROSC (1) and good outcomes have been reported even after 60 minutes of CPR (7). • Fluid responsiveness should be immediately assessed. Fluids are beneficial in most cases (7). • Amiodarone is a first-line agent in ventricular tachycardia and ventricular fibrillation (1). • Consider pacing for hemodynamically significant bradycardia (1). • In right heart failure, physiologic considerations include adequate filling, perfusion pressure (both systolic and diastolic systemic pressures), and inotropic support (7). • Embolic arrests, including venous air embolism, should be treated as right heart failure (7). • Wide-complex bradycardia and asystole are consistent with hyperkalemia. Early treatment with an IV calcium chloride bolus is indicated (7). • Emergency pacing is indicated for: – Bradycardia unresponsive to chronotropes (7) – Escape rhythms, drug overdose, acidosis, electrolyte abnormalities (7) – Significant sinus node dysfunction, Mobitz type II 2nd degree, 3rd degree heart block, alternating bundle branch block, or bifascicular block (1). – Overdrive pacing of tachycardias (supraventricular tachycardia or ventricular tachycardia) (7).

FOLLOW-UP

• During post-arrest care, one should consider: Targeted temperature management (therapeutic cooling) (1) and avoidance of hyperoxia (PaO2 >100 mm Hg) (7).

• Patients surviving anaphylaxis or malignant hyperthermia, or those with a difficult airway, should be given documentation they can bring for future operative encounters (7).

CLOSED CLAIMS DATA

• Death or brain damage was associated with induction of anesthesia in 62% of cases during 1985–1992, versus 35% of cases from 1993 to 1999 (8). • Caplan et al. describe 14 cases of high spinal, suggesting that bradycardia is an important early warning sign and that epinephrine is associated with ROSC (3).

Pregnancy Considerations

• The gravid uterus can compress the aorta and IVC after the 20th week of gestation. • Resuscitation of the mother may not be possible until the fetus is delivered by emergency hysterotomy. • During arrest, hysterotomy should be performed at the bedside since there is insufficient time to transport the patient to the OR.

Pediatric Considerations

• CPR recommendations in pediatric patients vary by the patient’s age. • Resuscitation drugs should be dosed according to the patient’s weight. • Intravenous access can be uniquely difficult in pediatric patients. Intraosseous lines are a method to get quick reliable access to the circulation. • Cardiac output in children frequently depends on heart rate (rather than on contractility), making the treatment of bradycardia an important part of pediatric resuscitation.

REFERENCES

1. American Heart Association. ACLS Provider Manual, 2010. 2. Newland MC, Ellis SJ, Lydiatt CA, et al. Anesthetic-related cardiac arrest and its mortality: A report covering 72,959 anesthetics over 10 years from a US teaching hospital. Anesthesiology. 2002;97:108–115. 3. Zuercher M, Ummenhofer W. Cardiac arrest during anesthesia. Curr Opin Crit Care. 2008;14:269–274. 4. Peterson GN, Domino KB, Caplan RA, et al. Management of the difficult airway: A closed claims analysis. Anesthesiology. 2005;103:33–39. 5. Gabrielli A, O’Connor MF, Maccioli GA. Anesthesia-centric ACLS. Available at: http://www.asahq.org/For-Members/Publications-and-Research/ ∼/media/For%2520Members/Publications/Other/Anesthesiology-CentricACLS.ashx. 6. Nichol G, Thomas E, Callaway CW, et al. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA. 2008;300:1423–1431. 7. Sprung J, Warner ME, Contreras MG, et al. Predictors of survival following cardiac arrest in patients undergoing noncardiac surgery: A study of 518,294 patients at a tertiary referral center. Anesthesiology. 2003;99:259–269.

8. Caplan RA, Ward RJ, Posner K, et al. Unexpected cardiac arrest during spinal anesthesia: A closed claims analysis of predisposing factors. Anesthesiology. 1988;68:5–11.

ADDITIONAL READING

• Cheney FW. The American Society of Anesthesiologist closed claims project: What have we learned, how has it affected practice, and how will it affect practice in the future? Anesthesiology. 1999;91:552–556. • Cheney FW, Posner KL, Lee LA, et al. Trends in anesthesia-related death and brain damage: A closed claims analysis. Anesthesiology. 2006;105:1081–1086.

CODES ICD9 427.5 Cardiac arrest ICD10 I46.9 Cardiac arrest, cause unspecified

CLINICAL PEARLS

• Cardiac arrest associated with anesthesia is different; good recovery is frequent with timely intervention. • Hypovolemia is a common cause of arrest and vigilance is important. Pulse pressure variation >15% can be an important clue to volume responsiveness. • Take no more than 10 seconds to find a pulse before starting compressions. • Bradycardia and asystole are often related to reversible factors.

ACROMEGALY Adam Thaler, DO

BASICS DESCRIPTION

• The term acromegaly comes from the Greek words for “extremities” and “enlargement.” • Acromegaly is a condition caused by an abnormal overproduction of growth hormone (GH) from the anterior pituitary, usually by a pituitary tumor. The result is an overgrowth of skeletal, soft, and connective tissues. Enlargement is seen in: – Major organs including the heart, lungs, liver, and kidney – Hands, feet, jaw, and tongue – Airway anatomy including the tongue, epiglottis, mandible, and generalized soft tissue (making airway management potentially difficult) EPIDEMIOLOGY Incidence

• Annual new patient incidence: 3–4 per million per year • In the US: 1:20,000 persons

Prevalence

• Most common age at diagnosis is 40–45 years. • All ethnic groups and gender are affected equally.

Morbidity

• Increased prevalence of cardiovascular risk factors • Difficult airways are seen in 10–43% of patients (compared to 3.6% in the general population). Mallampati Class I and II may present with airway difficulty in up to 20% of patients. Mortality

• Premature death can occur twice as frequently when GH concentration is >10 ng/mL. • Cardiovascular causes are the most frequent cause of death in untreated acromegaly; the majority of patients die before the age of 50 years. • Survival in patients with uncontrolled disease is reduced by an average of 10 years compared with age-matched controls. ETIOLOGY/RISK FACTORS

• No major risk factors • Weak risk factors include: – MEN type I syndrome – McCune–Albright syndrome

– Isolated familial acromegaly – Carney complex – Family history of aryl hydrocarbon-receptor interacting protein (AIP) mutation

PATHOPHYSIOLOGY

• Hypothalamus: Growth hormone-releasing hormone (GHRH) is produced and secreted by the hypothalamus via the hypophyseal tract to the anterior pituitary gland (as is somatostatin). • Pituitary gland: GHRH stimulates the anterior pituitary gland to produce and secrete GH into the bloodstream, whereas somatostatin inhibits GH production and secretion. • Tissues: GH travels to and stimulates the liver to produce another hormone called insulinlike growth factor 1 (IGF-1). IGF-1, in turn, promotes growth of bone and other tissues. • “Feedback loop”: Normally, levels of GHRH, GH, somatostatin, and IGF-1 are tightly controlled by each other. Levels are affected by: Sleep, exercise, stress, food intake, and blood sugar levels. • Excessive GH results from pituitary adenomas in >95% of cases. Secretion of GH by a pituitary tumor is not controlled by the feedback loop resulting in excessive IGF-1 with subsequent abnormal tissue growth. – Carbohydrate and fat processing is affected causing diabetes and high levels of fats in the blood. This, in turn, can lead to atherosclerosis and heart disease. – Myocardial growth can result in conduction disturbances. – Hepatomegaly – Kidneys: Positive fluid balance may be due to chronic hypertension, causing vasoconstriction, preoperative hypovolemia, lower cardiac output, fluid volume dysautoregulation, and/or renal dysfunction. – Lungs: Lower arterial pH – Tumors can also grow to considerable size and cause problems by pressing on and invading surrounding tissues. • Gigantism is the term used when acromegaly occurs in children.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients with acromegaly may have glottic or subglottic stenosis, nasal turbinate enlargement, vocal cord thickening, or recurrent laryngeal nerve involvement. Be aware of the potential for a difficult airway, perform a careful exam, and consider having backup airway devices available. • Address comorbid conditions including diabetes, hypertension, and cardiac disease.

PREOPERATIVE ASSESSMENT SYMPTOMS

• May be divided into 2 groups: Tumor compression of surrounding tissues or those caused by excess GH and IGF-1 in the blood. Compression of surrounding tissues can present as headaches or partial loss of vision in one or both eyes. Bitemporal hemianopsia is due to pressure on the optic chiasm.

• Pituitary tumors also can damage the pituitary gland itself, disrupting hormone production. Hormone imbalances are responsible for symptoms such as impotence, low sex drive, and changes in the menstrual cycle. • Symptoms due to excess GH or IGF-1 include increase in ring size or tightness of rings (“sausage-like” fingers), shoe size, sweating, jaw prominence, as well as coarseness or thickening of facial features (especially the nose), macroglossia, or skin tags. History

• Onset: The average time from onset to symptoms to diagnosis is 12 years. • Snoring may suggest obstructive sleep apnea; present in 75% of patients. If on CPAP, establish settings. • If the patient has diabetes mellitus, assess blood sugar control; present in 25% of patients.

Signs/Physical Exam

• Musculoskeletal: – Prognathism – Osteoarthritis – Osteoporosis – Kyphosis – Skeletal muscle weakness • Airway: – Macroglossia – Vocal cord thickening with hoarseness – Thickening of the laryngeal and pharyngeal soft tissues: Leading to subglottic narrowing – Enlarged epiglottis – Hypertrophy of the periepiglottic folds – Calcinosis of the larynx – Recurrent laryngeal nerve injury • Endocrine: – Peripheral neuropathy – Thyroid nodule; goiter (25%): May compress trachea • Cardiovascular: – Increased prevalence of valvular heart disease Significant AI (30%) Significant MR (5%) – Hypertension (46%)—volume overload Cardiomegaly Dysrhythmias (40%) LV dysfunction: EF ∼ 42% CHF (3–10%)

MEDICATIONS

• Octreotide is a somatostatin analog that inhibits GH secretion. It is capable of causing GI side effects such as nausea, bloating, and gas in up to 30% of patients. • Dopamine agonists, bromocriptine and cabergoline, work at the level of the pituitary to

reduce GH and subsequent IGF-1 secretion. • Pegvisomant is a GH receptor blocker and a new category of drugs. Studies have shown that it normalized IGF-1 levels in >90% of people treated. Side effects include reaction at the injection site, sweating, headache, and fatigue.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• GH and IGF-1 levels • GH suppression test is a confirmatory test measured before and after drinking 75 g of glucose. The inability to sufficiently suppress serum GH confirms the diagnosis. • ECG changes, such as ST-segment depression, T-wave abnormalities, and conduction defects, are noted in >50% patients. • Chest radiography can show bone thickening. • CT or MRI of the head to confirm that an adenoma is in the pituitary gland. • CT scans of the abdomen/pelvis and chest look for tumors of the pancreas, adrenal glands, ovaries, or lung that might secrete GH or GHRH.

CONCOMITANT ORGAN DYSFUNCTION • Hypertension • Diabetes mellitus • Arthritis • Colonic polyps • Coronary artery disease • Conduction disturbances

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Severe symptoms such as CHF or critical aortic stenosis • Returning GH levels to normal can reduce the incidence of upper respiratory tract complications. Regression of the mucosal hyperplasia and thickening could be achieved preoperatively.

CLASSIFICATIONS

• Biochemical criteria: – Elevated age- and sex-matched plasma IGF-1, random plasma GH >0.4 mcg/L, and lack of GH suppression below 1 mcg/L following an oral glucose load – Severity is judged according to GH levels, which correlate with the tumor mass. • Imaging criteria: Severity of pituitary adenoma judged according to: – Pituitary tumor volume – Suprasellar extension and compression of neural structures – Invasion of sphenoid bone and cavernous sinuses • Pathology criteria: Positive GH immunostaining confirms the diagnosis of a pituitary GHsecreting adenoma. On the basis of the number of cytoplasmic granules, somatotroph adenomas are divided into 2 types: – Densely granulated – Sparsely granulated (more aggressive)

TREATMENT PREOPERATIVE PREPARATION Premedications

• Antihypertensive medications, as needed • Insulin, as needed

INTRAOPERATIVE CARE Choice of Anesthesia

Regional blocks may be considered to avoid airway instrumentation; however, in the event of a complication, or failed block, it would require airway instrumentation in less than ideal conditions or emergently. Monitors

• Standard ASA monitors • Arterial line may be considered in patients with poorly controlled hypertension or diabetes, or with coronary artery disease. • Foley catheters may be placed to carefully monitor fluid management; patients may be 1,200–1,500 mL overloaded.

Induction/Airway Management

• Preparations should be made for a potential difficult airway. – Larger face mask may be required because of prognathism. – Smaller ETT may be needed because of subglottic narrowing and distortion. – If direct laryngoscopy is difficult, fiberoptic intubation can also be challenging.

Maintenance

• Balanced anesthetics with volatiles and intravenous agents have been utilized. • Hypertension may be seen intraoperatively, especially after the nasal septum is prepped with cocaine, epinephrine, or phenylephrine. • In patients with aortic regurgitation, “fast and loose” describes providing afterload reduction and higher heart rates. Bradycardia and increases in SVR increase the regurgitant volume in patients with aortic regurgitation. • Glucose monitoring may be necessary in long cases or in poorly controlled diabetics. • Fluid regulation may be altered: Urine output is significantly lower in acromegalic patients resulting in greater positive fluid balance.

Extubation/Emergence

Patients are at increased risk for airway obstruction and may have difficult airways; ensure that the patient is fully awake and following commands before extubating.

POSTOPERATIVE CARE BED ACUITY

• Consider supplemental oxygen (nasal cannula, face mask) • Prepare for the potential backward displacement of the already large tongue post-extubation that may cause respiratory compromise.

COMPLICATIONS

• Airway difficulties • Mild perioperative metabolic problems occur with respect to blood glucose and fluid balance.

REFERENCES

1. Nemerget EC, Dumont AS, Barry UT, et al. Perioperative management of patients undergoing transsphenoidal pituitary surgery. Anesth Analg. 2005;101:1170–1181.

2. Seidman PA, Kofke WA, Policare R, et al. Anaesthetic complications of acromegaly. Br J Anaesth. 2000;84(2):179–182. 3. Hakala P, Randell T, Valli H. Laryngoscopy and fiberoptic intubation in acromegalic patients. Br J Anaesth. 1998;80(3):345–347. 4. Scacchi M, Cavagnini F. Acromegaly. Pituitary. 2006;9(4):297–303. 5. Nabarro JD. Acromegaly. Clin Endocrinol (Oxf). 1987;26(4):481–512.

ADDITIONAL READING

• Katznelson L, Atkinson JL, Cook DM, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly-2011 update: Executive summary. Endocr Pract. 2011;17(4):636–646.

See Also (Topic, Algorithm, Electronic Media Element) • Cushing syndrome • Diabetes mellitus • Difficult airway

CODES ICD9 253.0 Acromegaly and gigantism ICD10 E22.0 Acromegaly and pituitary gigantism

CLINICAL PEARLS

• Greater than 50% of patients develop cardiac complications: Cardiomyopathy with arrhythmias, left ventricular hypertrophy, decreased diastolic function, hypertension • Greater than 60% of patients develop respiratory complications: Upper-airway obstruction with sleep apnea, associated with soft-tissue laryngeal airway obstruction and central sleep

dysfunction

ACUTE ADRENAL INSUFFICIENCY Cristina Cunanan, MD Anahat Dhillon, MD

BASICS DESCRIPTION

• Also called adrenal crisis, acute adrenal insufficiency is a life-threatening condition secondary to inadequate adrenal steroid production not matching increased demands during stress (e.g., infection, surgery) (1). • Manifestations result from mineralocorticoid deficiency, in association with prostaglandin excess, and decreased responsiveness to norepinephrine and angiotensin II (2): – Severe hypotension – Circulatory collapse – Hypothermia – Altered mental status – Hypoglycemia • Primary adrenal insufficiency (PAI) (3): – All 3 layers of the adrenal cortex are affected. – Involves glucocorticoid, mineralocorticoid, and adrenal androgen deficiencies – Seen with autoimmune adrenalitis, adrenal hemorrhage, adrenalectomy, AIDS, and tuberculosis • Secondary adrenal insufficiency (SAI) (2): – Results from disorders of the hypothalamic–pituitary–adrenal (HPA) axis that may involve tumors, irradiation, trauma, surgery, exogenous glucocorticoid therapy (most common), enzyme inducers that enhance the clearance of synthetic glucocorticoids (rifampin and carbamazepine), or drugs that inhibit cortisol synthesis (ketoconazole, etomidate) (3) – These conditions can cause a deficiency in adrenocorticotropic hormone (ACTH) or corticotropin-releasing hormone (CRH), leading to atrophy of the adrenal zona fasciculata where glucocorticoids are synthesized. – Mineralocorticoid function is better maintained, and hence, less likely to cause an adrenal crisis. • Initiation of thyroxine replacement in patients with hypothyroidism may induce adrenal crisis due to increased cortisol metabolism (4).

EPIDEMIOLOGY Incidence

3.3–6.3 adrenal crisis per 100 patient years (4,5) Prevalence

• Of PAI, 93–140 per million; age of diagnosis peaks in the 4th decade of life; women more frequently than men (5).

• Of SAI, 150–280 per million; age of diagnosis peaks in the 6th decade of life; women more frequently than men (5).

Morbidity/Mortality

• Data regarding morbidity and mortality in patients with adrenal insufficiency are scarce (6). • The risk ratio for death is more than 2-fold higher in patients with PAI; it is attributed to malignancy and cardiovascular and infectious diseases (7). • In patients with PAI, mean age at death for females is 75.7 years, and for males mean age is 64.8 (this is 3.2 and 11.2 years less than the estimated life expectancy, respectively) (8). • In children with PAI, there is a 3- to 4-fold increase in mortality compared with the general population (8).

ETIOLOGY/RISK FACTORS

• Risk of adrenal crisis is higher in: – PAI compared to SAI (3.3–6.6 per 100 vs. 2.5–5.8 per 100) – Women compared to men (4.4 per 100 vs. 1.6 per 100 years) (4,5) • In SAI patients, there is a higher risk of adrenal crisis in female patients and with the presence of diabetes insipidus. • Precipitating factors for adrenal crisis include (5): – Infectious disease (particularly GI infections) – Surgery – Strenuous physical activity – Cessation of glucocorticoid replacement – Psychic distress – Heat – Pregnancy

PHYSIOLOGY/PATHOPHYSIOLOGY

• HPA axis is vital to the body’s ability to cope with severe stress, such as that induced by natural or iatrogenic trauma or infection. • Adrenal cortex produces glucocorticoids (mainly cortisol) and mineralocorticoids (mainly aldosterone); these hormones are required for the maintenance of metabolic control, blood volume, and normal cardiovascular function. • Surgery, anesthesia, trauma, and severe illness result in elevated ACTH and cortisol levels, from a normal cortisol secretion rate of 10 mg/d to 75–150 mg/d during stress; and this response is absent in patients with adrenal insufficiency. • Mineralocorticoids are produced by the zona glomerulosa under the control of the renin– angiotensin system: – Facilitates sodium and potassium homeostasis and the maintenance of intravascular volume – Primary target is the kidney, where it stimulates reabsorption of sodium and secretion of potassium and hydrogen ions. – Deficiency results in salt wasting and volume depletion. • Glucocorticoids have multiple effects on body tissues including: – Increased gluconeogenesis

– Increased angiotensin synthesis by the liver – Increased vascular reactivity to vasoconstrictors – Decreased capillary permeability – Decreased production and activity of nitric oxide – Alteration of kinin and prostaglandin systems – Facilitate conversion of norepinephrine to epinephrine in the adrenal medulla • Glucocorticoid deficiency, therefore, results in decreased vascular responsiveness to angiotensin II and norepinephrine, decreased synthesis of renin substrate, and increased prostacyclin production which can aggravate the circulatory collapse seen in mineralocorticoid deficiency. • Chronic use of exogenous corticosteroids given in supraphysiologic doses leads to the development of SAI, and the amount of adrenal suppression depends on the dose, duration, frequency, time and route of administration and can occur as early as 1 week after commencing therapy (3).

PREVENTATIVE MEASURES

• Anesthetic plan should avoid the use of drugs that inhibit cortisol synthesis (e.g., etomidate) in patients at risk. • Controversy remains over whether supplemental perioperative steroids are required for patients on maintenance doses of corticosteroids who undergo surgery (9). A 2009 Cochrane review of randomized controlled trials of supplemental perioperative steroids concluded that there is inadequate evidence to support or refute the use of supplemental perioperative steroids, but it is likely that the administration of daily maintenance steroid dose may be sufficient and supplemental doses are not required. • While this topic is controversial and the optimal dose and duration of perioperative glucocorticoid coverage have also not been established, the following recommendations are based on a review of expert opinion and clinical experience (3): – For minimal stress procedures (<1 hour under local anesthesia), continue usual replacement corticosteroid dose. – For minor stress procedures (colonoscopy, inguinal hernia repair), administer IV hydrocortisone 25 mg or equivalent at the start of the procedure, followed by usual replacement doses after the procedure. – For moderate stress procedures (open cholecystectomy, joint replacement, lower limb revascularization, abdominal hysterectomy), administer IV hydrocortisone 75 mg/d on the day of the procedure (25 mg q8h), then taper over the next 1–2 days to usual replacement doses. – For severe stress procedures (cardiothoracic, Whipple, liver resection), administer IV hydrocortisone 150 mg/d (50 mg q8h), then taper over the next 2–3 days to the usual replacement dose.

DIAGNOSIS • History/physical exam – If PAI is undiagnosed and suspected, elicit symptoms such as chronic fatigue, weakness, lethargy, anorexia, weight loss, postural hypotension, recurring abdominal pain, loss of

libido, loss of axillary and pubic hair, and hyperpigmentation (2). – All of the above may be present in SAI, except for hyperpigmentation, and hypotension may be less prominent (2). – Any patient who has received the equivalent of 20 mg/d of prednisone for >5 days is at risk for suppression of the HPA axis; if on therapy for 1 month, HPA axis suppression can last up to 6–12 months after cessation of therapy (10). – Other modes of steroid administration should be noted, such as topical, inhaled, and regional (10). • Maintain a high level of suspicion for adrenal crisis in cases of unexplained hypotension refractory to catecholamines, especially in patients with increased risk (e.g., prior glucocorticoid therapy, autoimmune disease, AIDS) (2). • ACTH stimulation test involves the administration of cosyntropin 250 mcg IV (synthetic ACTH hormone), followed by serum cortisol measurements at 30 minutes and 60 minutes. Plasma cortisol values: – <3 mcg/dL (80 nmol/L) is highly suggestive of adrenal insufficiency. – <10 mcg/dL (275 nmol/L) requires further adrenal evaluation. – >20 mcg/dL (550 nmol/L) makes adrenal insufficiency highly unlikely (2). • Morning plasma cortisol levels – 10–20 mcg/dL is normal. – <3 mcg/dL is highly suggestive of adrenal insufficiency (2). • Other tests: – Elevated plasma corticotropin levels in PAI – Decreased aldosterone levels – Hyperreninemia – Hyponatremia – Hyperkalemia – Hypoglycemia – Eosinophilia – TSH

DIFFERENTIAL DIAGNOSIS • Cardiogenic shock • Anaphylactic shock • Hypovolemic shock

TREATMENT • Immediate administration of hydrocortisone 100 mg IV followed by 100–200 mg IV per 24 hours • IV fluids • Electrolyte replacement • Improvement in response to glucocorticoids is usually seen within 12 hours (2). • If diagnostic screening demonstrates basal or post-ACTH cortisol levels >20 mcg/dL, stop further hydrocortisone therapy unless the patient is still critically ill.

FOLLOW-UP • If hemodynamic stability is recovered after administration of glucocorticoid, may consider continuing with surgical procedure. • Final confirmation of adrenal insufficiency and evaluation of its etiology, if unknown, may be appropriate after resolution of the acute crisis.

REFERENCES

1. Hahner S, Allolio B. Therapeutic management of adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2009;23(2):167–179.

2. Bouillon R. Acute adrenal insufficiency. Endocrinol Metab Clin North Am. 2006;35(4):767– 775. 3. Jung C, Inder WJ. Management of adrenal insufficiency during the stress of medical illness and surgery. Med J Aust. 2008;188(7):409–413. 4. Hahner S, Loeffler M, Bleicken B, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: The need for new prevention strategies. Eur J Endocrinol. 2010;162(3):597– 602. 5. Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003;361:1881–1893. 6. Schulman D, Palmert MR, Kemp SF, et al. Adrenal insufficiency: Still a cause of morbidity in childhood. Pediatrics. 2007;119:e484–e494.

7. Bergthorsdottir R, Leonsson-Zachrisson, M, Oden A, et al. Premature mortality in patients with Addison’s disease: A population-based study. J Clin Endocrin Metab. 2006;91:4849– 4853. 8. Erichsen M, Løvås K, Fougner KJ, et al. Normal overall mortality rate in Addison’s disease, but young patients are at risk of premature death. Eur J Endocrinol. 2009;160:233–237. 9. Yong SL, Marik P, Esposito M, et al. Supplemental perioperative steroids for surgical patients with adrenal insufficiency. Cochrane Database Syst Rev. 2009;7(4). 10. Kohl B, Schwartz S. Surgery in the patient with endocrine dysfunction. Anesthesiol Clin. 2009;27:687–703. See Also (Topic, Algorithm, Electronic Media Element) • Cortisol • Ulcerative colitis • Rheumatoid arthritis

CODES ICD9 255.41 Glucocorticoid deficiency ICD10

• E27.2 Addisonian crisis • E27.40 Unspecified adrenocortical insufficiency

CLINICAL PEARLS

• Risk of adrenal crisis is significantly higher in PAI than in SAI. • The body makes approximately 10 mg/d of cortisol. During extreme stress 75–150 mg/d can be made. • Any patient who receives >20 mg/d of prednisone equivalent for >5 days is at risk for SAI. • There is inadequate evidence to support empiric use of supplemental corticosteroids in patients with risk factors for SAI.

ACUTE NORMOVOLEMIC HEMODILUTION Teresa L. Moon, MD

BASICS DESCRIPTION

• Acute normovolemic hemodilution (ANH) is a strategy that may be implemented to decrease the need for blood transfusions and their associated risks; it is a form of autologous blood transfusion. Other commonly utilized techniques include preoperative autologous donation and cell salvage. • The process of ANH entails the controlled removal of whole blood from the patient prior to incision and blood loss and simultaneous replacement with an appropriate volume of crystalloid or colloid (non-red cell containing), in order to maintain normovolemia and avoid hypotension. • The goal is to decrease the loss of red cell mass (as well as other blood cells and proteins) during surgical bleeding. ANH has the following advantages: – No risk of transfusion error – No risk of disease transmission – Simple – Inexpensive – Minimal use of collective resources – Stored in the operating room – Whole blood with all components is returned to the patient; minimal loss of coagulation factors and platelets secondary to limited storage time. – Does not require significant coordination with the patient and blood bank (unlike autologous blood donation) PHYSIOLOGY PRINCIPLES

• Transient intraoperative anemia is achieved by removing whole blood to a target hematocrit while concurrently administering crystalloid or colloid to maintain normovolemia. By decreasing the hematocrit, there is a reduced loss of erythrocyte mass during surgical bloodshed. • Hemodynamics during dilutional anemia – Combination of decreased blood viscosity and local vasoregulatory factors. The endothelium senses changes in intraluminal blood flow, shear stress, and the chemical environment that result from hemodilution and changes in cardiac output; it appears to respond by releasing NO and causing vasodilation. Additionally, studies have suggested that hemodilution may decrease the blood’s ability to scavenge and inactivate NO (results in increased levels). Autonomic nervous system-mediated vasodilation does not appear to play a significant role. – Cardiac output is increased (stroke volume) secondary to decreased viscosity (decreased afterload/tension of the left ventricle); the myocardium is capable of ejecting more

volume. – Mean arterial pressure is usually maintained within the limits of normal, secondary to the compensatory increase in cardiac output. – Heart rate may increase with profound anemia. • Critical red cell mass: A concept that describes the lower limit of hemoglobin that is capable of maintaining effective oxygen delivery. Below this threshold, ischemia and anaerobic metabolism/lactate production can result. • Unlike techniques such as deliberate hypotension, ANH does not directly decrease surgical blood volume loss.

ANATOMY

• Phlebotomy may be performed via a: – Large vein in the periphery; newly placed or pre-existing large-bore IV catheter or onetime stick – Central line – Arterial line

DISEASE/PATHOPHYSIOLOGY

• Decreased blood oxygen carrying capacity occurs secondary to hemodilution. Studies have demonstrated that tissue oxygenation is usually not sacrificed if normovolemia is maintained. • Cardiac ischemia: Usually presents with tachycardia and ECG changes as a result of decreased oxygen delivery • Edema may be present postoperatively if large volumes of crystalloid and/or colloids are used to maintain normovolemia.

PERIOPERATIVE RELEVANCE

• Indications: – Spinal surgery – Prostatectomy – Hysterectomy – Hip arthroplasty – Major liver resections: The reported rate of blood transfusion is rarely <30% and patients normally require 1–2 units. One study demonstrated that the use of ANH did not result in adverse cardiac, renal, or neurologic outcomes. Benefit were particularly pronounced in patients who had significant blood loss that exceeded 800 mL. • Contraindications: – Pre-existing anemia – Unstable angina – Coronary artery disease with significant stenosis or recent myocardial infarction in the last 6 months – High-grade aortic stenosis or carotid stenosis – Renal impairment – Bacteremia • Invasive monitors may be needed to closely monitor the effects of anemia, including volume

status and frequent blood draws in order to monitor oxygen delivery, confirm EBL, and electrolytes. The extent of monitoring should factor in comorbidities, the extent of hemodilution, and expected blood loss. • Collection: – Phlebotomy: Whole blood is collected immediately prior to, or during, the initial stages of surgery (ideally prior to any blood loss). – Fluid replacement: May be done with either crystalloid or colloid to maintain normovolemia – Storage: Whole blood is collected into blood-collection bags with a predetermined anticoagulant (usually CPD) and kept in the operating room. Agitation of the bags throughout the case can decrease clotting. • Considerations: – Patient becomes unstable during hemodilution: May be evidenced by unexplained tachycardia or ECG changes despite normal intravascular volume. Phlebotomy should be halted and blood returned to the patient in order to avoid any acute cardiac events. – Patient becomes unstable intraoperatively: The removed blood may need to be transfused to treat severe anemia. Should be administered prior to donated blood. – May be utilized with cell salvage techniques; however, should not be combined with deliberate hypotension. • Determining the amount of blood to be collected: – Safe hematocrit: A standard, agreed-upon post-hemodilution value does not exist. Target levels usually range from 20% to 28% and are dependent upon myocardial oxygenation needs, as well as comorbidities (in particular cardiac and cerebral disease). – Red cell mass: Dependent on starting hematocrit and total blood volume. Healthy patients with normal and high hematocrits and men have a greater amount of red cells that can be collected (compared to those who are chronically ill, anemic, or women). – Anticipated surgical blood loss • Efficacy of ANH is dependent upon: – Volume removed: Patients that can tolerate a large volume of blood removal will likely have a higher final hematocrit once surgical bleeding has stopped and the blood is returned. Whereas patients who are unable to donate as much blood will clearly not receive as much red blood cell mass when blood is returned. – Effectiveness of hemodilution: Inadequate volume repletion, initially or intraoperatively, can result in hemoconcentration and increased red blood cell mass. – Timing of autologous blood replacement: If the collected blood is returned after surgical bleeding is complete, the patient will have less absolute red cell losses.

EQUATIONS

• Estimated blood volume (EBV) – Male: 70 mL/kg – Female: 60 mL/kg • Blood volume to be withdrawn = EBV × (Hctinitial – Hcttarget)/Hctaverage • For a 70 kg man with a starting Hct of 40% •

• ?> and target Hct 28%: [(70 mL/kg × 70 kg) × (40 − 28)]/[(40 + 28)/2] = 1,729 mL • For a 70 kg man with starting Hct of 35%: [(70 mL/kg × 70 kg) × (35 − 28)]/[(35 + 28)/2] = 1,089 mL • Volume replacement with appropriate amounts of crystalloid (3 × volume withdrawn) or colloid (1 × volume withdrawn)

REFERENCES

1. Doss DN, Estafanous FG, Ferrario CM, et al. Mechanism of systemic vasodilation during normovolemic hemodilution. Anesth Analg. 1995;81:30–34. 2. Epstein NE. Bloodless spinal surgery: A review of the normovolemic hemodilution technique. Surg Neurol. 2008;70:614–618.

3. Matot I, Scheinin O, Jurim O, et al. Effectiveness of acute normovolemic hemodilution to minimize allogenic blood transfusion in major liver resections. Anesthesiology. 2002;97:794–800. 4. Monk TG. Acute normovolemic hemodilution. Surg Infect. 2005;6(Suppl 1):S9–S15. 5. Murray D. Acute normovolemic hemodilution. Eur Spine J. 2004;13(Suppl 1):S72–S75. 6. Pape A, Habler O. Alternatives to allogenic blood transfusions. Best Pract Res Clin Anesthesiol. 2007;21(2):221–239. See Also (Topic, Algorithm, Electronic Media Element) • Cell salvage • Autologous blood transfusion • Anemia • Myocardial oxygen supply • Blood oxygen carrying capacity

CLINICAL PEARLS

• Normovolemic hemodilution is a technique that can help prevent or decrease the need for allogenic blood transfusion in patients who can sustain moderate anemia intraoperatively. • In comparison to autologous or homologous blood transfusions, normovolemic hemodilution eliminates the need for blood bank storage or testing. Since the collected blood remains in the operating room with the patient, transfusion errors and disease transmission are eliminated. • The amount of whole blood collection is directly related to the preoperative hematocrit. Safe post-hemodilution hematocrits depend upon surgical blood loss and comorbidities. • The efficacy of ANH has produced conflicting results, which have been attributed to the heterogeneity of the surgeries it is used for, differences in study protocol, as well as the definition of outcome variables. • During cardiopulmonary bypass grafting, when ANH was implemented in lieu of homologous blood transfusion, significantly lower bilirubin levels were observed. However, it may be associated with increased postoperative bleeding.

ACUTE RESPIRATORY DISTRESS SYNDROME Carlos A. Puyo, MD

BASICS DESCRIPTION

• Acute respiratory distress syndrome (ARDS) is a form of noncardiogenic pulmonary edema. It results from lung inflammation and presents as acute hypoxemia and bilateral pulmonary infiltrates. – Acute lung injury (ALI) is a milder form of ARDS. – Hyaline membrane disease is a pediatric form of ARDS (caused by a decrease in surfactant). • Causes stem from either pulmonary or extrapulmonary sources. • Histologically, affected alveolar units are filled with protein-rich edematous fluid and cellular debris; this occurs in a heterogenous manner. • Diagnosis is based on the history, ABG, and chest radiography. • Treatment consists of supportive measures (supplemental oxygen, mechanical ventilation) while the lungs heal. EPIDEMIOLOGY Incidence

In the US, approximately 200,000 cases per year Morbidity

• Can lead to multiorgan failure syndrome, GI ulcers, cardiac dysfunction, acute renal failure, malnutrition, and chronic issues such as myopathy and psychiatric problems • Lung function recovers significantly 6–12 months after initial injury.

Mortality

Estimated 25–40%, but is influenced by a variety of coexisting conditions such multisystem organ failure ETIOLOGY/RISK FACTORS

• Lung dysfunction due to direct lung injury: – Pneumonia (frequent cause, high mortality) – Aspiration – Mechanical ventilation – Lung contusion – Inhalational injury – Near drowning • Extrapulmonary sources: – Sepsis (frequent cause, high mortality; elderly patients are more susceptible)

– Trauma – Pancreatitis – Polysubstance abuse: Cocaine, opioid – Massive blood transfusions – Ischemia-reperfusion injury – CNS injury – Air/fat embolism – Cardiopulmonary bypass

PHYSIOLOGY/PATHOPHYSIOLOGY

• Early: “Exudative phase” translates into ventilation/perfusion mismatch (shunting) and hypoxia, decreased lung compliance, and increased work of breathing. It is associated with the following: – Diffuse alveolar and capillary endothelial injury – Influx of protein-rich fluid into alveoli – Release of tumor necrosis factor, interleukin-1, and interleukin-8 – Procoagulant activity as protein C and S levels fall and levels of tissue factor and plasminogen activator inhibitor-1 increase – Pneumocyte type 1 apoptosis with resultant accumulation of necrotic cellular debris in the alveolar lumen. Pneumocyte type 2 dysfunction reduces surfactant production. • Late: Fibroproliferative changes occur later and are characterized by: – Chronic inflammation resulting from the proliferation of pneumocyte type 2 and macrophages, and neutrophils filling the alveolar space. – Fibrosis (associated with increase mortality). – Neovascularization

PREVENTATIVE MEASURES

• Pneumonia should be diagnosed and treated aggressively. • Identify patients at risk for pulmonary aspiration (e.g., full stomach, reflux disease, active vomiting, recent oral contrast for radiological study, altered mental status) and implement appropriate maneuvers to reduce risk (gastric tube suctioning, prokinetic agents, reverse Trendelenburg, rapid sequence induction). • Mechanical ventilation should be weaned as tolerated. • Prevention of multiorgan dysfunction: – Diagnose and treat sources of infection aggressively (e.g., urinary tract infection in the elderly) to avoid sepsis. – Limit blood transfusions, as appropriate. Consider blood salvaging techniques, blood filters, and collection from donors without multiple HLA exposures.

DIAGNOSIS • The diagnosis of ARDS can coexist with other (extrapulmonary) diagnoses. – History: Acute dyspnea or hypoxemia related to trauma, sepsis, drug overdose, massive transfusion, aspiration, or acute pancreatitis – Physical examination: Tachypnea and tachycardia are nonspecific. Auscultation may

reveal bilateral rales. Cyanosis, fever, hypothermia. – ABG: PaO2/FiO2 ratio <200; a ratio <300 suggests ALI. Initially a respiratory alkalosis is seen. If ARDS is secondary to sepsis, the ABG may reveal a respiratory acidosis with or without respiratory compensation. – CXR is initially patchy and located peripherally; it progresses rapidly to diffuse bilateral involvement with a ground-glass appearance. – PCWP ≤18 mm Hg with no clinical evidence of cardiac failure. – TEE may be helpful to determine pulmonary artery pressures and intravascular volume status. – CT scan: Heterogeneous alveolar involvement

DIFFERENTIAL DIAGNOSIS

• Interstitial/idiopathic pulmonary fibrosis • Lymphangitic carcinoma • Veno-occlusive pulmonary disease • Intravascular fluid overload • Pneumonia and respiratory failure: Ventilator-associated pneumonia, viral, bacterial • Pulmonary hemorrhage • Near drowning • Drug reaction toxicity: Heroin, salicylate • Cardiac disease: Left ventricle failure, mitral stenosis • Toxic shock syndrome • Tumor lysis syndrome

TREATMENT • Nonpharmacologic interventions are supportive and consist of intubation and mechanical ventilation: – Tidal volume (6 mL/kg) using predicted body weight and plateau pressures of ≤30 cm H2O (Level I evidence per the ARDS Network trial)

– Positive end-expiratory pressure (PEEP); higher PEEP levels do not negatively impact lowVT strategy. – Prone positioning can improve oxygenation and mortality (Level I evidence). – Permissive hypercarbia allows for decreased minute ventilation with consequent decreases in shear injury that is imposed on the alveoli with positive pressure ventilation. The pH should be maintained at ≥7.20. – Extracorporeal membrane oxygenation and extracorporeal carbon dioxide removal; no outcome improvement has been demonstrated with these techniques. – Recruitment maneuvers expand atelectatic areas and improve ventilation/perfusion matching. However, they are ineffective in providing sustained oxygen concentration. – Pressure–volume curve to set VT and PEEP; has uncertain clinical value. – Open-lung strategy applying high-pressure ventilation (55 cm H2O) for 5–10 minutes and PEEP of 16 cm H2O has uncertain value.

– High-frequency oscillatory ventilation and bilevel ventilation improve oxygenation transiently with no benefit in mortality. • Pharmacologic interventions: – Fluid management: A conservative or restrictive strategy can improve oxygenation. It has been associated with decreased morbidity and mortality. – Inhaled nitric oxide (INO): Provides short-term reduction of pulmonary artery pressures and oxygen improvement (Level I evidence) – N-acetylcysteine and procysteine have some benefit in improving lung injury score. – Corticosteroids and methylprednisolone have been used with benefit in ALI/ARDS patients diagnosed with Pneumocystis carinii pneumonia or at high risk for fat emboli. High doses may benefit patients with unresolved ARDS of more than 7 days duration. – Nutritional support: Diets with high-fat content and antioxidant nutrition. The use of eicosapentaenoic acid (EPA) and gamma-linoleic acid (GLA) appears to decrease inflammation mediated by arachidonic acid metabolites. Evidence exists to support the use of EPA and GLA in ARDS. – Surfactant: Evidence demonstrates that there is a lack of improvement in oxygenation, ventilator- free days, or mortality. – Partial liquid ventilation appears to reduce inflammation and disease progression, but has no obvious benefit in ventilator dependency and mortality. – Ibuprofen and NSAIDs do not control inflammation mediated by sepsis and are likely of no benefit in ARDS. – Ketoconazole, pentoxifylline, lisofylline: Studies have not demonstrated a benefit. • Diagnose and provide supportive therapy for extrapulmonary manifestations: – Renal: Monitor for acute tubular necrosis – Hepatic: Monitor liver function test for abnormalities such as cholestasis and hepatocellular injury – Hematologic: Monitor for thrombocytopenia, disseminated intravascular coagulation, and changes in Von Willebrand factor

FOLLOW-UP After resolution of the acute phase, mechanical ventilation and respiratory therapy should be administered to regain muscle strength.

REFERENCES

1. Bernard GR. Acute respiratory distress syndrome. Am J Respir Crit Care Med. 2005;172:798–806. 2. Briel M, Meade M, Mercat A, et al. Higher versus lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: Systematic review and meta-analysis. JAMA. 2010;303(9):865–873. 3. Kallet RH. Evidence-based management of acute lung injury and acute respiratory distress syndrome. Resp Care. 2004;49(7):793–809. 4. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as

compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301–1308.

See Also (Topic, Algorithm, Electronic Media Element) • Aspiration • Noncardiogenic pulmonary edema • Burns • Pressure volume loops • Respiratory system compliance • Positive end expiratory pressure (PEEP)

CODES ICD9 518.82 Other pulmonary insufficiency, not elsewhere classified ICD10 J80 Acute respiratory distress syndrome

CLINICAL PEARLS

• Frequent evaluation of respiratory and hemodynamic status • Since sepsis is the most common risk factor for ARDS, infectious sources must be sought aggressively. • If transportation is required, consider maintaining respiratory ventilation with an ICU ventilator.

ADRENALECTOMY Joe C. Hong, MD

BASICS DESCRIPTION General

• Adrenalectomy is indicated for any malignant lesion, suspicious lesion, or hormonesecreting lesion of the adrenal gland. • The laparoscopic approach is considered when the lesion is nonmalignant and has the benefit of reduced pain, faster recovery, and fewer complications. • Open adrenalectomy is indicated for large or malignant tumors where en bloc resection and local dissection may be necessary. It can be performed via an anterior, posterior, or thoracoabdominal approach. – The anterior approach allows access to the entire peritoneal cavity and the ability to treat bilateral adrenal disease or other intra-abdominal pathology. However, it is a major laparotomy with the potential for prolonged ileus, pulmonary dysfunction, and pain. – The posterior approach allows avoidance of the thoracic and peritoneal cavities; this reduces bowel injury or pulmonary problems. However, it is limited to tumors <5 cm and precludes exploration of metastases or other intra-abdominal pathologies. – The thoracoabdominal approach allows wide direct exposure for larger tumors and en bloc resection of a single adrenal gland. However, it limits intraperitoneal exploration, and if the other gland needs to be removed, it requires repositioning and a second incision. Position

• Laparoscopic: Lateral decubitus position with the operative side up. The table is flexed at the waist with the patient in a slight reverse Trendelenburg position to facilitate placement of the laparoscopic ports. • Open adrenalectomy: Supine position

Incision

• Laparoscopic: 4 laparoscopic ports, 2 cm below the respective costal margin and spaced no less than 5 cm apart • Open: Either a unilateral subcostal, bilateral subcostal, or midline incision is used.

Approximate Time

• Laparoscopic: Typically 2.5–3.5 hours • Open: Typically 2–3 hours with additional time when local invasion of nearby structures is present EBL Expected

• Laparoscopic: 50 mL

• Open: 100–200 mL

Hospital Stay

• Laparoscopic: Routine cases in relatively healthy patients can be discharged within 24 hours. Longer in-hospital stay is dependent on patient comorbidities, need for blood pressure monitoring, or adjustment of steroid replacement therapy. • Open: Postoperative in-hospital stays of 4–5 days are typical.

Special Equipment for Surgery

• Laparoscopic instruments and ultrasonic or bipolar coagulator • Invasive monitoring and possibly a transesophageal echocardiogram for management of patients with pheochromocytoma

EPIDEMIOLOGY Incidence

• Incidental finding on abdominal CT scan ranges from 0.6% to 1.3% (1). • Autopsy finding in patients who had no evidence of adrenal disease: 1.4–9%

Prevalence

• Nonfunctional adrenocortical adenomas: 70% (2) • Adrenal metastasis: 21% • Pheochromocytomas: 11% • Cortisol-producing adenomas: 2–15% • Aldosteronomas: 2% • Adrenocortical carcinomas: 1.2%

Morbidity

• Depends on the nature of the adrenal mass • Aldosteronomas may have marked hypertension, hypokalemia, and metabolic alkalosis. • Cortisol-producing adenomas may have labile diabetes in addition to marked hypertension, hypokalemia, and metabolic alkalosis. • Pheochromocytoma may have significant cardiac morbidity induced by long-standing catecholamine excess, hypertension, arrhythmias, dilated and hypertrophic cardiomyopathy, and congestive heart failure.

Mortality

Dependent on the nature of the adrenal mass

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Understanding the physiologic implications of the hormonally active adrenal mass is vital to appropriate anesthetic management. • Patients with aldosteronoma should have their antihypertensive medication (most commonly spironolactone) maintained up to the time of surgery. Careful cardiac assessment is necessary since these patients have increased cardiac comorbidity. Serum sodium and especially serum potassium should be checked prior to surgery. Severely hypokalemic

patients should have their potassium replaced preoperatively. • Patients with Cushing syndrome must have their diabetes, blood pressure, intravascular volume status, and electrolytes optimized prior to surgery. Their Cushingoid habitus (central obesity, moon facies, buffalo hump) may present an airway challenge. Hydrocortisone supplementation at the time of surgery is needed since they are at increased risk of developing acute glucocorticoid deficiency postoperatively. • Patients with pheochromocytoma must be adequately alpha-blocked, volume resuscitated, and concomitant organ dysfunctions identified and optimized prior to surgery. Phenoxybenzamine is the alpha-blocker of choice. Intraoperatively, hypertension is expected during tumor manipulation whereas hypotension is expected after ligation of the tumor’s venous drainage (3). • Nonfunctional masses are relatively straightforward with anesthetic goals geared toward each patient’s comorbidities.

PREOPERATIVE ASSESSMENT SYMPTOMS

Due to mass effect and/or physiologic effects of excess hormone production History

Based on the nature of the adrenal mass. In patients with hormone-producing adrenal lesions, a careful history of the medical management of the endocrinopathy is necessary. This includes the type and dosage of medication, clinical response to therapy, and relevant comorbidities. Signs/Physical Exam

• Cortisol-producing adenoma: Steroid encephalopathy, central obesity, moon facies, thick neck, muscle wasting, osteoporosis, virilization and infertility, glucose intolerance, hypertension, hypokalemia, alkalosis, easy bruising, poor wound healing (2) • Aldosteronoma: Hypertension, hypokalemia, alkalosis, hypernatremia, left ventricular hypertrophy (4) • Pheochromocytoma: Hypertension, arrhythmias, cardiomyopathy, congestive heart failure, glucose intolerance (3)

MEDICATIONS •

Cortisol-producing adenoma: Hypoglycemic agents, potassium antihypertensives • Aldosteronoma: Spironolactone, potassium supplements, antihypertensives • Pheochromocytoma: Alpha-adrenergic antagonists

supplements,

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Evaluation of hormonal function is based on concomitant signs and symptoms. • Cortisol-producing adenoma: Dexamethasone suppression test, plasma ACTH, urine-free

cortisol • Aldosteronoma: Potassium level, aldosterone:renin ratio • Pheochromocytoma: 24-hour urine catecholamine and metanephrines

CONCOMITANT ORGAN DYSFUNCTION

Cardiac dysfunction in the form of left ventricular hypertrophy is common in patients with aldosteronoma and pheochromocytoma. In addition, cardiac comorbidity induced by longstanding catecholamine excess is prominent in patients with pheochromocytoma. These include hypertension, arrhythmias, dilated and hypertrophic cardiomyopathy, and congestive heart failure.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Standard anxiolytic titrated to comfort • In patients undergoing adrenalectomy for pheochromocytoma, benzodiazepines and opioid premedication are helpful for awake arterial line placement. • Patients with cortisol-producing tumors and those undergoing bilateral adrenalectomy must receive perioperative intravenous hydrocortisone. Special Concerns for Informed Consent

If planned, risks specific to central venous and epidural catheter placement should be discussed. Antibiotics/Common Organisms

• First-generation cephalosporin, such as cefazolin, is recommended prior to surgical skin incision. • Clindamycin is an alternative for a cephalosporin allergy.

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia is the technique of choice. • Epidural analgesia for postoperative pain may be helpful for patients undergoing open adrenalectomy. Monitors

• Standard ASA monitors • Invasive monitoring is dictated by patient comorbidities. • Pheochromocytoma: Arterial line for hemodynamic monitoring and a central line for infusion management and vasoactive medications. Pulmonary artery catheter or TEE may be needed if significant catecholamine-induced cardiomyopathy is present (3).

Induction/Airway Management

• Induction and airway management is dictated by preoperative airway assessment. • Pheochromocytoma: A deep plane of general anesthesia is needed prior to attempted laryngoscopy and intubation. • Cortisol-producing adenomas: Cushingoid habitus (central obesity, moon facies, buffalo hump) may complicate airway management.

Maintenance

• Inhalational anesthesia with opioid supplementation is suitable. • Nitrous oxide should be avoided because bowel distension may limit the visibility of the surgical field in both laparoscopic and open adrenalectomy. The increased incidence of pneumothorax after open adrenalectomy also makes nitrous oxide relatively contraindicated.

Extubation/Emergence

General extubation criterion can be used.

POSTOPERATIVE CARE BED ACUITY

• For routine uncomplicated procedures, a standard floor bed is usually adequate. • Patients with pheochromocytoma with persistent labile blood pressure requiring postoperative infusion of vasoactive medications should be monitored in the ICU.

ANALGESIA

• Laparoscopic adrenalectomy is well tolerated. Patients are typically able to convert from intravenous to oral analgesics on postoperative day 1. • Epidural analgesia provides excellent pain relief for open adrenalectomy. • Patient-controlled analgesia (PCA) may be used for patients undergoing open adrenalectomy without epidural analgesia.

COMPLICATIONS

• Intraoperative complications include massive bleeding due to the proximity of the renal artery, renal vein, vena cava, and aorta. • Hypertensive, as well as hypotensive crises, can occur during adrenalectomy for pheochromocytoma. Postoperatively, these patients may be at risk for hypotension and hypoglycemia. • Acute adrenal insufficiency can occur after resection of a cortisol-producing adrenal mass or after bilateral adrenalectomy. Perioperative hydrocortisone 100 mg IV q8h is recommended. • Injury to pancreas resulting in pancreatitis • Injury to diaphragm and pneumothorax • Conversion from laparoscopic approach to open adrenalectomy • Peritoneal carcinomatosis

PROGNOSIS

Dependent on the type, malignant nature, and degree of local and distant invasion

REFERENCES

1. Brunt LM, Moley JF. Adrenal incidentaloma. World J Surg. 2001;25(7):905–913.

2. Cook DM. Adrenal mass. Endocrinol Metab Clin North Am. 1997;26(4):829–852.

3. Kinney MA, Narr BJ, Warner MA. Perioperative management of pheochromocytoma. J Cardiothorac Vasc Anesth. 2002;16(3):359–369. 4. Young WF Jr. Adrenal causes of hypertension: Pheochromocytoma and primary aldosteronism. Rev Endocr Metab Disord. 2007;8(4):309–320.

ADDITIONAL READING

• Graham GW, Unger BP, Coursin DB. Perioperative management of selected endocrine disorders. Int Anesthesiol Clin. 2000;38(4):31–67. • Lampe GH, Roizen MF. Anesthesia for patients with abnormal function of the adrenal cortex. Anesthesiol Clin North Am. 1987;5:245–268.

See Also (Topic, Algorithm, Electronic Media Element) • Pheochromocytoma • Aldosterone • Cortisol

CODES ICD9

CLINICAL PEARLS

• Understanding the physiologic implications of the hormonally active adrenal mass is vital to appropriate anesthetic management. • Patients undergoing bilateral adrenalectomy will need perioperative stress dose steroids. Postoperatively, they will need glucocorticoid and mineralocorticoid replacement. • Patients with cortisol-producing adrenal lesions also need perioperative stress dose steroids. The quiescent contralateral adrenal gland will be unable to produce enough cortisol in the immediate postoperative period. • Patients with pheochromocytoma must be adequately alpha-blocked prior to adrenalectomy. • Pneumothorax should be considered if the patient develops postoperative respiratory distress.

AFTERLOAD

Viachaslau Barodka, MD

BASICS DESCRIPTION

• Left ventricular (LV) afterload is the force against which the heart must work to generate pump work (eject blood out of the heart into the aorta). • In the purest form, afterload is defined as wall stress, which are the forces opposed to ventricular fiber shortening. Afterload or wall stress provides the most accurate indication of cardiac energy expenditure. However, clinically true afterload or wall stress cannot be measured. PHYSIOLOGY PRINCIPLES

• Ventricular afterload is comprised of a static and dynamic component; elevation in either component may result in increased afterload. – Static component of the LV is comprised of the systemic vascular resistance (SVR) or outflow of blood into resistance arterioles. Under normal physiologic circumstances and in healthy (compliant) vasculature, the SVR is the main determinant of LV afterload. Small arteries and arterioles are referred to as resistance vessels since they are the principal site of SVR. The autonomic nervous system provides constant regulation on a short time scale (seconds to minutes). SVR; Normal 800–1400 dyne-s/cm5. SVR can be calculated from MAP, CVP, CO; SVR = [(MAP – CVP) × 80]/CO. The pressures are measured from the “beginning” of the circuit to the “end” of the circuit. For example, if the CO is 5 L/min, the BP is 120/80 mm Hg (MAP is 93.3 mm Hg), and the CVP is 12 mm Hg, then SVR = [(93.3–12) × 80]/5 = 1396 dyne-s/cm5. The static component of the right ventricle (RV) is composed of the pulmonary vascular resistance (PVR); normal 80–120 dyne-s/cm5. The blood flow (CO) through the left and right sides of the heart are equal; however, the afterload for the RV is significantly less. The main component of RV afterload is PVR, which is around 10 times lower than SVR. The formula to calculate is: PVR = [(Mean PAP – wedge pressure) × 80]/CO. The pressures are measured from the “beginning” of the circuit to the “end” of the circuit. For example, if the PA pressures is 25/10 mm Hg (Mean PAP is 15 mm Hg), the wedge pressure is 8 mm Hg, and CO is 5 L/min, then PVR = [(15–8) × 80]/5 = 112 dynes/cm5. – Dynamic pulsatile component: Consists of 2 phasic elements; one is the compliance-related forward pulse wave and the second is the reflected pulse wave. The pulsatile component contributes significantly to total LV afterload in stiff vessels. Central arterial vessels are the principal site of the pulsatile component. • Despite the clinical use of SVR to determine LV afterload, it is best measured as systolic wall stress. Stress (or tension) is defined as the force, or load, per unit cross-sectional area. Wall

stress/tension is the product of transmural pressure and chamber radius divided by the wall thickness. For the LV: S = PR/2h; where S is the LV wall stress, P is the LV cavity pressure, R is the radius of the LV, and h is the myocardial thickness (also known as LaPlace’s Law). – LV cavity pressure During systole, the LV generates pressure. That pressure should be higher than pressure seen by the LV in the ascending aorta at each point in time during ejection to promote forward blood flow. Pressure in the ascending aorta will depend on the peripheral resistance, compliance of the arterial tree, and contributions of wave reflections. Aortic valve: Any obstruction to flow from the LV cavity to the ascending aorta will cause additional resistance and a necessary increase in the LV cavity pressure to overcome it. Clinically, the most common causes are aortic stenosis and hypertrophic obstructive cardiomyopathy which can cause up to 100 mm Hg extra LV pressure over what is needed to pump blood into aorta. Blood viscosity contributes to the resistance to blood flow, such that increased viscosity leads to increased resistance. The blood viscosity depends, for the most part, on the hematocrit. – Radius: Wall stress (afterload) is dependent on the geometry of the LV itself. During systole, the ventricular wall thickens and the radius decreases as the ventricle pumps blood out (and reduces LV wall stress). Preload or LV end diastolic volume affects the initial radius and, hence, wall stress during isovolemic contraction. – Myocardial thickness: In cases of pressure overload, and resultant increases in wall stress, the heart muscles compensate by becoming hypertrophic (wall stress is inversely related to wall thickness, thus myocardial hypertrophy decreases wall stress). Increased muscle mass requires less force per unit area. – Wall stress or afterload varies over time since the LV pressure, radius, and wall thickness are continuously changing throughout the cardiac cycle. As a result, afterload can be calculated at the instant of aortic valve opening, at the end of ejection, or at any instant throughout systole. Clinical investigators use peak systolic stress, end-systolic stress, or mean systolic wall stress as indices of afterload. • Determinants/regulation of vascular resistance (and hence afterload) – Neurohumoral responses (long-term regulation, over days and weeks) Renin–angiotensin axis: Juxtaglomerular cells in the kidneys secrete renin directly into the blood. The secreted renin then converts angiotensinogen (released by the liver) to angiotensin I. Angiotensin I is subsequently converted to angiotensin II by the enzyme angiotensin-converting enzyme (produced by the lungs). Angiotensin II is a potent vasoactive peptide that causes blood vessels to constrict, resulting in increased SVR. Vasopressin (antidiuretic hormone) is secreted into the blood by the neurohypophysis. It activates specific vasopressin receptors on the VSMC and causes vasoconstriction. – Nitric oxide (NO) is produced by endothelial cells, diffuses into the media, and relaxes the VSMC by activating cyclic guanylate cyclase. Hence, NO is called endothelium-derived relaxation factor. Smoking, hypercholesterolemia, oxidative stress, or limited physical exercise can result in endothelial dysfunction; consequently, there is a decrease in NO production (increase in SVR). – Hydrogen sulfide has been recently recognized as endothelium-derived hyperpolarizing

factor. Similar to nitric oxide, hydrogen sulfide causes relaxation of resistance arterioles, vasodilation, and decreases the SVR.

ANATOMY

• The mean pressure decreases by only 1–2 mm Hg between the ascending aorta and peripheral arteries in compliant and healthy vasculature, indicating low resistance at this portion of the vascular tree. • A major drop of pressure occurs over small arterioles and they constitute the major site of resistance.

DISEASE/PATHOPHYSIOLOGY

• Increased afterload: – Aortic stenosis: The LV needs to generate increased force to overcome the resistance of the stenosed aortic valve and eject blood into the aorta. This results in increased LV wall tension and stress (increased afterload). The LV usually compensates with a hypertrophic response to return the wall stress to normal. The thickened LV, in conjunction with increased force, however, increases the myocardial oxygen demand (increased muscle mass working harder) and decreases the myocardial oxygen supply, especially to the endocardium. Blood flows from the epicardium into the endocardium; additionally, it takes more time for blood to flow across a thickened LV wall to reach the endocardium. – Chronic hypertension: Essential hypertension in the young and middle-aged population is frequently characterized by increases in DBP. This is the result of vasoconstrictory responses predominating over vasodilatory responses at the level of the arterioles in the periphery. In the elderly, the predominant form of hypertension is systolic hypertension, while DBP is low to normal (the SVR in isolated systolic hypertension is usually normal or even decreased). However, there is a marked increase in vascular sclerosis, stiffness, and arterial impedance. The increased resistance is to the pulsatile (dynamic) component of blood flow. In either case, untreated or poorly controlled hypertension requires the heart to work harder, increases afterload, and often elicits a compensatory hypertrophic response in the LV to return wall stress to normal. – Hemoconcentration: Analogous to the reservoir bag on the anesthesia machine; if the bag was filled with water or jelly as opposed to air, it would require more energy to compress or squeeze the bag. – Increased LV radius: A dilated LV, as with cardiomyopathy or heart failure, causes increases in wall tension due to decreased myocardial thickness as well as increased radius ( = increase in afterload). This is analogous to the reservoir bag overfilled; more energy would be required to empty the bag, compared to a partially or normally filled bag. – Cor pulmonale: Elevated PVR requires the RV to squeeze harder to generate more force to eject blood ( = increased afterload for the RV). Elevations in the PVR over prolonged time lead to compensatory RV hypertrophy to decrease wall tension and normalize the afterload. • Decreased afterload – Sepsis: Mostly due to loss of SVR – Anaphylaxis: Mostly due to loss of SVR – High-output cardiac failure: Due to arteriovenous shunts

– Anemia: Due to both a decrease in viscosity and lowered SVR (decreased BP) – Hypovolemia: There is less blood to stretch the LV and, hence, less force is needed to eject blood. To counteract for reductions in the stroke volume (and maintain BP), the sympathetic tone is increased (increase in SVR and heart rate).

PERIOPERATIVE RELEVANCE

• Increased afterload – Sympathetic stimulation with intubation and surgery – Vasopressors: Preferential alpha-1 agonists have the most profound effect on increasing the afterload (phenylephrine and norepinephrine). Vasopressin Ephedrine and epinephrine will increase afterload in addition to increasing contractility. • Decreased afterload – An increasing depth of anesthesia with either volatile agents or IV anesthetics (e.g., propofol) causes a decrease in sympathetic tone (vasorelaxation) with resultant decreases in the SVR and BP. Increased depth should be avoided in hypovolemia or hypotensive patients. – Neuraxial techniques: Both spinal and epidural blocks interrupt conduction of nerve impulses through sympathetic fibers at the level of their spread. This leads to a decrease in sympathetic tone, SVR, and preload (pooling of blood in veins). To counteract this response, volume resuscitation and pressors may be administered as needed. In hypovolemic or hemorrhaging patients, neuraxial techniques should not be used; they block compensatory increases in SVR and heart rate. – NO donors (nitroglycerin, nitroprusside) cause relaxation of both resistance arterioles and veins and, hence, a decrease in SVR and preload. They are used for tight BP control in procedures such as AAA and CEA. – Inhaled NO is used to alleviate increased pulmonary artery pressures. It has minimal systemic effects. – Calcium channel blockers cause arterial smooth muscle relaxation and decrease myocardial contractility. – Phosphodiesterase inhibitors increase cardiac contractility while relaxing resistance arterioles, decreasing SVR, and causing hypotension. They are mostly used in heart failure, but may also require simultaneous administration of alpha-agonists to counteract pronounced hypotension. – Positive end expiratory pressure (PEEP). LV dysfunction with pulmonary edema results in decreased pulmonary volume and compliance. Greater negative inspiratory pressures (and hence transmural pressures) are required to expand the lungs. PEEP can partially offset this.

EQUATIONS

• SVR = [(MAP – CVP) × 80]/CO; MAP = mean arterial pressure (mm Hg), CVP = central venous pressure (mm Hg), CO = cardiac output (liters/minute) • PVR = [(mPAP – wedge pressure) × 80]/CO; mPAP = mean pulmonary artery pressure (mm Hg), CO = cardiac output (liters/minute)

• Tension = (ΔP × R)/H × 2; ΔP = change in pressure, R = radius, H = wall thickness O’Rourke M, Nichols W. McDonald’s blood flow in arteries. Hodder Arnold, 2006.

REFERENCES

1. Thiele RH, Nemergut EC, Lynch C. The physiologic implications of isolated alpha1 adrenergic stimulation. Anesth Analg. 2011;113(2):284–296.

2. Thiele RH, Nemergut EC, Lynch C. The clinical implications of isolated alpha1 adrenergic stimulation. Anesth Analg. 2011;113(2):297–304. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary artery catheter waveforms • Anaphylaxis • Hypertension • Aortic stenosis • Positive end expiratory pressure (PEEP)

CLINICAL PEARLS

• The SVR is considered by most professionals as equivalent to afterload and is substituted for it; SVR is calculated from MAP and CO (SVR = MAP/CO). SVR is an oversimplified quantification of the true resistance force against which the heart works. It has an underlying assumption that flow is constant.

AIRWAY FIRE

Charles E. Cowles, Jr., MD

BASICS DESCRIPTION

• Surgical fires can occur either on the patient or in the patient’s airway (1). They are most commonly observed during procedures that involve the open delivery of oxygen near an ignition source, like electrocautery or laser. • Airway fires are defined as either within the airway or within the breathing circuit. Many fires occur during relatively minor procedures of the head and neck which involve the use of a cautery device and a simple facemask or nasal cannula. • As with operating room (OR) fires, airway fire prevention depends on: – An understanding of how triad elements (ignition, fuel, oxidizers) interact to create a fire – Recognizing how standard OR equipment, materials, and supplemental oxygen can become one of those elements – Vigilance for circumstances that bring fire triad elements into close proximity (2)

EPIDEMIOLOGY Prevalence

• Occurs in about 650 cases per year (1:87,646) (3,4) • Actual incidence is likely higher, but surgical fires are under-reported.

Morbidity

20–30 serious injury cases per year (3)

Mortality

2–3 deaths per year (3)

ETIOLOGY/RISK FACTORS

• High-risk procedure: Use of an ignition source in close proximity to an oxidizer (oxygen and nitrous oxide) (1). Fires have been reported during head and neck procedures including tracheostomies, adenotonsillectomies, endoscopic airway surgeries, and cutaneous surgeries of the head and neck. • Monitored anesthesia care (MAC)/sedation cases, especially when there is/are: – Open delivery of oxygen at a FiO2 >30%

– Drapes and towels configured in a manner to “trap” oxygen underneath drapes and allow for significant accumulation. – Patients with obstructive sleep apnea or other diseases (decreased functional residual capacity) that cannot tolerate sedation without oxygen supplementation – Surgeries that involve the head and neck or are above the xiphoid process • Laser use in or near the airway

• Prep solution and drapes: – Adequate drying time is not observed when using alcohol-based preps or if pooling of prep has occurred. – Flammable prep solutions are used in hairy locations or crevasses of the body or if largesized sponge containers (26 mL) are used for head and neck cases.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Fire occurs when elements of the fire triangle are combined (3): – Ignition source Electrosurgical units (ESU), cautery, lasers, and light sources Usually controlled by the surgeon – Fuel Alcohol-based preps, towels, and drapes Usually controlled by the OR nurse – Oxidizers Oxygen and nitrous oxide Usually controlled by the anesthesia provider • Fires which occur in oxygen-enriched environments may result in a sudden flash fire where the burn injuries occur in a matter of seconds (too quickly for extinguishment).

PREVENTATIVE MEASURES

• Often, fires are the result of a lack of communication among surgical team members. • Injury and damages commonly occur when the response to the fire is uncoordinated and haphazard. • Assess the fire risk prior to every surgical procedure; this is especially important for cases involving the head and neck or cases performed under MAC. – Perform fire risk assessment during surgical “time out” – Assign specific tasks for each OR team member to perform in case of a fire • MAC/sedation cases with increased fire risk – Do not use supplemental oxygen unless clinically necessary – Allow sufficient time for oxidizer levels to drop before using an ignition source. This may take several minutes. – If an FiO2 >30% is required: Communicate with the surgical team. Titration of the FiO2 can be accomplished with the use of an oxygen blender or by using

the common gas outlet found on some anesthesia machines. Consider using an ETT or supraglottic device such as the laryngeal mask airway (LMA) to eliminate the open flow of oxygen, especially in cases above the xiphoid Configure drapes to prevent accumulation of oxygen and to facilitate open ventilation. • Prep solution and drapes – Allow flammable surgical preps such as alcohol-based solutions to dry fully before the application of surgical drapes or barriers – Assess for pooling as a routine part of the time-out process – Avoid 26 mL applicators in head and neck cases

• General anesthetics, particularly for procedures above the xiphoid – Use cuffed tracheal tubes when possible – FIO2 <30% may reduce the risk of fire, particularly for intraoral cautery.

– Decreasing the electrocautery wattage may reduce the incidence of airway fires (5). • Laser procedures – Use an appropriate laser tube for the type and frequency of the laser – Use an indicator dye such as methylene blue in the distal cuff of laser tubes to detect inadvertent rupture – Moisten gauze or sponges if used to pack the airway – Participate in OR-specific fire drills which include the practice of patient evacuation methods and involvement of all team members, including surgeons and anaesthetists • Know the location of fire extinguishers and gas cut-off valves before the case begins • Consider assembling a cart for high-risk procedures which includes saline or water bottles, fire extinguishers, and placards to guide response

PREOPERATIVE ASSESSMENT • By index of suspicion and investigation of any smell of smoke, hearing loud “pop,” or seeing smoke or flames • Excessive movement of the patient during MAC • Alcohol burns with a nearly invisible flame which becomes increasingly difficult to see under bright surgical lights.

TREATMENT The following steps should be carried out as soon as possible. The specific order or sequence is not as important as rapidly completing the task (1): • Stop the procedure to evaluate situation • Stop the flow of gases • Remove endotracheal tube (ETT) • Remove drapes • Pour saline or water in airway

FOLLOW-UP • In the non-intubated patients, assess for smoke inhalation injury. • In intubated patients: – Examine the removed ETT for fragments that could still be present in the airway – Re-establish ventilation but avoid the use of oxidizers to avoid re-kindling of embers which may be present in the airway – Perform rigid bronchoscopy if lower airway injury is suspected (1) • Use fire extinguisher if initial attempts to extinguish the fire are not successful. Plan to evacuate the OR if necessary.

• If fire or smoke is present, activate the facility fire alarm system, notify the local fire department, and file a report with the fire marshal’s office according to local protocols • Transfer to appropriate burn facility

CLOSED CLAIMS DATA

• Claims approaching $1.5 million per case have been paid for MAC cases resulting in fatal or disfiguring burn injuries. • Most cases involve head and neck surgeries. • 74% of burn cases involve oxygen supplementation.

REFERENCES

1. merican Society of Anesthesiologists (ASA) Task Force on Operating Room Fires, Caplan RA, Barker SJ, et al. Practice advisory for the prevention and management of operating room fires. Anesthesiology. 2008;108(5):786–801. 2. Rinder CS. Fire safety in the operating room. Curr Opin Anaesthesiol. 2008;21(6):790–795. 3. ECRI New Clinical Guide to Surgical Fire Prevention [guidance article]. Health Dev. 2009;38(10):319. 4. ennsylvania Patient Safety Authority. Three “never complications of surgery” are hardly that. Pa Patient Saf Advis. 2007;4(3):82. 5. oy S, Smith LP. What does it take to start an oropharyngeal fire? Oxygen requirements to start fires in the operating room. Int J Pediatr Otorhinolaryngol. 2001;75(2):227–230.

ADDITIONAL READING

• Anesthesia Patient Safety Foundation (APSF). Prevention and management of surgical fires [video]. APSF, 2009. • Barker SJ, Polson JS. Fire in the operating room: A case report and laboratory study. Anesth Analg. 2001;93:960–965. • Department of the Army. Headquarters, United States Army Medical Command. Fires associated with the performance of surgical procedures [online]. MEDCOM Regulation No. 40-48, August 2003.

See Also (Topic, Algorithm, Electronic Media Element) • Smoke inhalation injury • Burns • Operating room fires

CLINICAL PEARLS

• Open delivery of oxygen should only be used as clinically necessary; oxygen concentrations >30% pose a fire risk. • Special precautions should be observed for high-risk procedures where use of an ignition source is in close proximity to an oxidizer. • Nitrous oxide supports combustion to the same extent as oxygen.

• Investigate sounds, smells, and noises that could be associated with OR fires. • In MAC/sedation cases, replace supplemental oxygen with an ETT or supraglottic device if the patient condition requires >30% oxygen when an ignition source is used.

ALCOHOL ABUSE

Zhuang-Ting Fang, MD, MSPH

BASICS DESCRIPTION

• Alcohol abuse is a chronic disease with profound societal implications. More than 19% of cases resulting in deaths of young automobile drivers were related to alcohol. Additionally, the annual total cost of alcohol-related problems reaches a staggering $180 billion. • Both acute alcohol intoxication and chronic alcohol abuse can increase anesthetic complications. EPIDEMIOLOGY Prevalence

In the US, the rate of alcohol use disorders, including abuse and dependence, is ~8.26%; this correlates to ~15 million people. Morbidity

• In the perioperative period, patients with alcohol abuse have been shown to have an increased risk of infections, bleeding disorders, need for ventilator support, and cognitive dysfunction. • Maternal alcohol consumption during pregnancy can lead to fetal alcohol disorders; 1% incidence. Mortality

• Alcohol withdrawal during surgery may be associated with a mortality rate as high as 50%. • Alcohol use is the third leading cause of preventable death in the US, and accounts for ∼85,000 deaths annually. ETIOLOGY/RISK FACTORS

• Gender: Men are 5 times more likely than women to develop alcohol abuse. • Family history: The rate of alcohol abuse is about 30% in men with one alcoholic parent. • Genetic factors: May affect the process and response to alcohol in the human body • Cultural factors: The high rate of alcohol abuse in the US and Europe may relate to the common use and social acceptance of alcohol use. • Psychiatric disorders: Higher in persons with depression, anxiety, antisocial behaviors, posttraumatic stress disorder, high self-expectations, or low frustration tolerance PATHOPHYSIOLOGY

• Alcohol has been shown to affect the following receptors in the human brain: – GABA: Alcohol binds to the GABA receptor and increases chloride ion movement into the cell with resultant hyperpolarization (decreases neural activity, by making the cell

membrane potential more negative). Responsible for the sedative and anxiolytic effects (similar to hypnotic drugs and benzodiazepines). – Glycine: Alcohol binds to the glycine receptor and potentiates its role as the major inhibitory neurotransmitter in the spinal cord and brain stem. – Serotonin: Alcohol increases levels either via increased release and/or decreased breakdown, as well as potentiates its effects on receptor function. Serotonin may enhance the release of other neurotransmitters that play a key role in tolerance and contribute to alcohol withdrawal syndrome (AWS). – Glutamate: Alcohol decreases glutamate’s excitatory effect on NMDA receptors. Chronic consumption, however, makes NMDA receptors hypersensitive to glutamate while desensitizing the GABAergic receptors; believed to play a role in AWS. – Opiates: Alcohol induces the release of endogenous opioid peptides (can cause euphoria and blunt the sensation of pain). The body’s endogenous opioid system (enkephalins, endorphins) is linked with the brain’s reward pathway; may play a role in addiction. – Dopamine: The increased levels/effects that are seen with alcohol abuse is a poorly understood mechanism. It has been postulated to result from disinhibition of dopaminergic neurons, decreased breakdown, and increased release. Dopamine pathways play a role in reward and reinforcement and may play a role in addiction. • Alcohol is absorbed directly through the stomach wall (∼20%) and small intestines (∼80%). The liver functions to break down alcohol. • Effects on other organs may result from direct inflammation or possibly from “blood sludging.” Blood sludging describes the clumping of red blood cells with resultant plugging of small vessels, ischemia, and cell/tissue death distally. The increased pressure can result in capillaries breaking (red eyes, blotchy skin, “drinker’s nose”).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperative evaluation should determine concomitant organ dysfunction. A high index of suspicion for alcohol cardiomyopathy should be present, as this is often underdiagnosed. • Prevent aspiration in patients with cirrhosis and ascites • Anticipate prophylaxis and treatment of alcohol withdrawal and delirium tremens

PREOPERATIVE ASSESSMENT SYMPTOMS

• A high index of suspicion is required to diagnose alcohol abuse. • Nonspecific, but suggestive, symptoms include gastritis, tremor, and history of falling.

History

• Despite the brief preoperative encounter, a social history including alcohol use should be elicited. If suspected, consider further focused questioning. • Alcohol Use Disorders Identification Test (AUDIT) is 92% effective in detecting hazardous or harmful drinking. A total score of ≥8 indicates harmful drinking behavior. It is also helpful in identifying those at greatest risk for postoperative complications. • Inquire about other substances of abuse

Signs/Physical Exam

• Usually nonspecific; abnormalities are usually related to the systemic diseases associated with chronic use. • “Drinker’s nose”: A purple nose that results from tiny broken capillaries

MEDICATIONS

No specific medications, unless being treated for abuse. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Glucose: May be low, particularly in diabetics • CBC with platelets: Anemia • Liver function tests, PT and aPTT: May be abnormal due to alcoholic hepatitis or cirrhosis. • EKG: May show left ventricular hypertrophy and arrhythmias. • CXR: May show aspiration, pleural effusions and cardiomegaly.

CONCOMITANT ORGAN DYSFUNCTION

• Nervous system: Cerebellar degeneration, tremors, delirium tremens, dementia, depression, memory loss, Wernicke–Korsakoff syndrome, peripheral neuropathy (burning, numbness, weakness) • Cardiovascular: Alcoholic cardiomyopathy, hypertension • Pulmonary: Aspiration, pleural effusion, and pulmonary hypertension (may occur in end stage liver disease). • Hepatic: Alcoholic hepatitis, cirrhosis • Gastrointestinal: Absorption of B vitamins and other nutrients may be impaired. Gastritis, ulcers, and increased risk of stomach cancer. Acute and chronic pancreatitis; may eventually result in diabetes. • Metabolic: Impairs fat and glucose metabolism in the liver and pancreas. Acute alcohol ingestion can result in a steep rise in blood sugar that is met by an increased release of insulin, with resultant hypoglycemia. • Hematologic: Anemia can result from malnutrition or direct suppression of bone marrow. • Malnutrition is very common and can lead to anemia (folic acid, vitamin B12 deficiency), or hypoalbuminemia (low protein intake) and Wernicke–Korsakoff syndrome (vitamin B1 deficiency). • Other: Sexual dysfunction (decreased testosterone), birth defects, osteoporosis

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Elective surgery should be postponed in patients with acute alcohol toxicity, alcoholic hepatitis, or decompensated systemic diseases. • Treatment of alcohol abuse or dependence should be considered before elective surgery in order to decrease perioperative morbidity and mortality. • Severe dehydration or electrolyte imbalance should be corrected prior to surgery.

CLASSIFICATIONS

• Alcohol abuse is defined by the following characteristics: Drinking even when it is dangerous; excessive drinking; legal problems related to drinking; and interpersonal problems with family, coworkers, and friends because of alcohol use. • Alcohol dependence (alcoholism) is characterized by: Drinking excessive amount frequently; the inability to stop drinking despite social, psychiatric, or medical complications; increased tolerance of alcohol; and the occurrence of alcohol withdrawal symptoms when drinking is discontinued.

TREATMENT PREOPERATIVE PREPARATION Premedications

Benzodiazepines are helpful in reducing anxiety and preventing withdrawal. INTRAOPERATIVE CARE Choice of Anesthesia

Regional anesthesia (spinal, epidural, or peripheral nerve blocks) may decrease systemic effects and CNS disturbance with general anesthesia. It is also easier to monitor mental status changes in awake patients, especially in those at risk of alcohol withdrawal. In patients with liver disease, however, coagulopathy may preclude neuraxial techniques. Monitors

• Standard ASA monitors • Invasive monitoring may be considered when alcoholic cardiomyopathy is suspected or present, and depending upon the surgical procedure. Induction/Airway Management

• Acute alcohol intoxication may reduce anesthetic dose requirement. • Chronic alcohol abuse may require higher anesthetic doses due to cross-tolerance (e.g., increased propofol induction doses). Cirrhotics have an increased volume of distribution which may necessitate increased doses (but may have increased sensitivity to drugs and decreased clearance). In alcoholic cardiomyopathy, intravenous induction should be accomplished by careful titration to avoid hypotension. • Rapid-sequence induction with cricoid pressure should be considered in patients with delayed gastric emptying due to ascites. Intoxicated trauma patients are at an increased risk for aspiration. Maintenance

• In cirrhotic patients, maintenance doses may need to be decreased due to impaired liver metabolic function. • Non-depolarizing muscle relaxants should be cautiously titrated due to impaired hepatic function. • “Banana bag” infusion may be considered.

Extubation/Emergence

Normal extubation criteria apply; however, alcoholics may have impaired clearance of muscle relaxants and gastric motility. Ensure full recovery from NMBDs and a protective gag reflex.

FOLLOW-UP BED ACUITY

• ICU admission may be required if alcohol withdrawal or delirium tremens is suspected. • Supplemental oxygen should be provided, especially when the patient is receiving narcotics.

COMPLICATIONS

• AWS may be seen in patients who abuse or are dependent on alcohol when they stop drinking abruptly because of injury, surgery, or acute illness. Typically develops 6–24 hours after their last drink. Symptoms are related to autonomic hyperactivity and include sweating, nausea, vomiting, anxiety, agitation, tachycardia, and hand tremor. Neuronal excitation, including grand mal seizures, usually occurs within 24–48 hours of abstinence. Delirium tremens is the most intense and serious form of AWS. It is characterized by visual or auditory hallucinations, confusion, clouding of consciousness, impaired attention, and pronounced autonomic hyperactivity. It usually appears 2–4 days after the patient’s last use of alcohol. Death from cardiovascular and respiratory collapse may occur, if untreated. Prophylaxis is with benzodiazepines. Treatment of AWS involves establishing the diagnosis and severity with the CIWA-Ar Score and transferring to the ICU. Medical treatment involves a combination of benzodiazepines, haloperidol, clonidine, and beta-blockers; in some instances, a drink with meals may be ordered. Supportive care includes the treatment of nutritional deficiency, hypoglycemia, arrhythmias, congestive heart failure, alcoholic hepatitis, alcoholic pancreatitis, GI bleeding, and nervous system impairment. • Postoperative cognitive dysfunction is increased in patients aged 55 years and older after noncardiac surgery with general anesthesia. • Increased risk of infections may be due to alteration of T-cell mediated immunity as well as altered immune response to surgical stress.

REFERENCES

1. Lian J, Cagetti E, Richard W, et al. Altered pharmacology of synaptic and extrasynaptic GABAA receptors on CA1 hippocampal neurons is consistent with subunit changes in a model of alcohol withdrawal and dependence. J Pham and Exp Therap. 2004;310(3):1234– 1245. 2. Lovinger DM. Serotonin’s role in alcohol’s effects on the brain. Alcohol Health Res World. 1997;21(2):114–120. 3. Publications from the Institute on Alcohol Abuse and Alcoholism, NIH. www.niaaa.nih.gov.

4. Spies CD, Rommelspacher H. Anesthestic alcohol withdraw in the surgical patients: Prevention and treatment. Anesth Analg. 1999;88:946–954. See Also (Topic, Algorithm, Electronic Media Element)

• Alcohol cardiomyopathy • Pregnancy substance abuse • Cirrhosis • Alcohol withdrawal syndrome

CODES ICD9

• 303.90 Other and unspecified alcohol dependence, unspecified • 305.00 Alcohol abuse, unspecified • 305.01 Alcohol abuse, continuous ICD10 • F10.10 Alcohol abuse, uncomplicated • F10.129 Alcohol abuse with intoxication, unspecified • F10.20 Alcohol dependence, uncomplicated

CLINICAL PEARLS

AUDIT (Alcohol Use Disorders Identification Test) utilizes 10 questions; scoring is on a scale of 0–4 per question. A total score of ≥8 indicates alcohol abuse or dependence. (Note: A unit is equal to one small glass of wine, a single purchased measure of spirits or half a pint of beer.) The questions include: • How often do you have a drink containing alcohol? • How many units of alcohol do you drink on a typical day when you are drinking? • How often do you have 6 or more units of alcohol on one occasion? • How often during the last year have you found that you were not able to stop drinking once you had started? • How often during the last year have you failed to do what was normally expected from you because of drinking? • How often during the last year have you needed a first drink in the morning to get yourself going after a heavy drinking session? • How often during the last year have you had a feeling of guilt or remorse after drinking? • How often during the last year have you been unable to remember what happened the night before because you had been drinking? • Have you or someone else been injured as a result of your drinking? • Has a relative or friend or doctor or another health worker been concerned about your drinking or suggested you should cut down?

ALCOHOL WITHDRAWAL SYNDROME Martin M. Stechert, MD Christopher G. Choukalas, MD, MS

BASICS DESCRIPTION

• Alcohol withdrawal syndrome (AWS) develops after the cessation of chronic alcohol use/abuse, generally within 6–48 hours. Alcohol abuse is characterized by impaired control over drinking, preoccupation with alcohol, use of alcohol despite adverse consequences, and denial. • AWS exists as a spectrum of presentations: – Mild: Cravings and psychomotor agitation – Severe: Hallucinations, autonomic instability (sweating, tachycardia, hypertension), fever, and disorientation. This constellation of symptoms is known as delirium tremens (DT). • If withdrawal symptoms are not present within a week after the last alcohol consumption, future development is unlikely. EPIDEMIOLOGY Prevalence

In general, outpatient estimates are between 4% and 15%, whereas 15–40% of all inpatients are thought to have abuse or withdrawal. Of those who experience withdrawal symptoms, 5% have severe symptoms characterized as DT. Morbidity

• AWS: Dysrhythmias, myocardial ischemia, delirium, and seizures • Chronic alcohol abuse: Immunosuppression, wound infections, malnutrition, and the complications of cirrhosis and liver failure Mortality

• Has decreased over time; historical estimates from severe AWS or DT reached levels as high as 40%, but the current rate is probably under 5%. • Results from dysrhythmia, aspiration pneumonia, or underlying illness that may have been the cause of alcohol cessation in the first place (e.g., infection, pancreatitis, etc.). ETIOLOGY/RISK FACTORS

• Alcohol use and abuse are obvious risk factors for developing AWS. Use and abuse are associated with a number of demographic characteristics, including: – Male sex – Lower socioeconomic status – White or Native American ethnicity – Certain psychiatric conditions (e.g., depression, anxiety disorders)

• Risk factors for the development of DT include: – Previous history of DT – Presence of AWS despite elevated level of blood alcohol – History of sustained drinking

PHYSIOLOGY/PATHOPHYSIOLOGY

• The pathophysiology of AWS is probably related to the neurophysiologic changes thought to be caused by chronic alcohol use. Although the functional consequence of receptormediated effects of alcohol remain to be elucidated, ingested ethanol has a number of receptor targets: – NMDA-related transmission is reduced. – GABA function is enhanced. – Glycine transmission (complex and location specific) are enhanced – Cholinergic and serotonergic activities are enhanced. • In order to maintain a normal arousal state, an adaptive response to chronic alcohol exposure yields decreased GABAA sensitivity and increased NMDA sensitivity. When ethanol is acutely withdrawn, reduced central inhibition (via GABAA) and aberrant activation of

excitatory NMDA receptors appear to be responsible for the acute withdrawal symptoms, including altered mental state and noradrenergic overdrive during AWS.

PREVENTATIVE MEASURES

• Prevention of AWS is a crucial aspect of treatment in the clinical arena, whereas public health efforts to curb alcohol abuse are necessary to prevent AWS on a societal level. • Perioperatively, prevention of AWS starts with an early identification of patients at risk for this condition. – The duration of potential abstinence from alcohol should be discussed with the primary care physician and the patient, and possible management solutions must be negotiated with the patient. – Nutrition including multivitamin administration should be optimized preoperatively. – Optimal medical management can be organized according to the degree of risk going into withdrawal, including additional invasive monitoring intraoperatively and appropriate designation (ICU, TCU) postoperatively. – Long-acting benzodiazepines (e.g., chlordiazepoxide) administered preoperatively may reduce the severity of AWS.

PREOPERATIVE ASSESSMENT • AWS is a clinical diagnosis and requires a detailed history and physical examination. – Key elements of the history include chronic alcohol use, recent cessation, and determining whether cessation was caused by some other illness. – Screening tools like the PAT (Paddington Alcohol Test) and AUDIT (Alcohol Use Disorders Identification Test) questionnaires can identify patients at risk for AWS. • Clinical manifestations of alcohol withdrawal often follow a timely schedule after the last consumption of alcohol:

– Early symptoms, including anxiety, tremulousness, palpitations, nausea, anorexia, typically begin after 6–8 hours. – Generalized seizures typically occur after 6–48 hours. – Alcoholic hallucinations after 12–48 hours – Delirium tremens after 48–96 hours • The latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) provides more precise diagnostic criteria that can be summarized as 2 or more of the following signs and symptoms occurring (1) in the context of cessation or reduction of previously heavy alcohol use and (2) not due to some other medical or mental disorder: – Sweating or tachycardia – Hand tremor – Insomnia – Nausea or vomiting – Hallucinations – Agitation – Anxiety – Generalized tonic–clonic seizure • It is important to note that in an anesthetized patient, symptoms may be obscured and limited to sympathetic surge (i.e., tachycardia, hypertension).

DIFFERENTIAL DIAGNOSIS

• Other causes of agitation and tremor, including caffeine overdose, cocaine and other stimulant use, as well as withdrawal from nicotine, illicit drugs, and medications (e.g., clonidine) • Other causes of hallucinations such as psychotic disorders, acute intoxication, sleep withdrawal, and drug side effects • Other causes of seizures such as metabolic or electrolyte derangements, intracranial pathology, meningitis, or underlying seizure disorder • Other hyper-metabolic syndromes that can mimic DT, such as malignant hyperthermia, thyroid storm, neuroleptic malignant syndrome, and serotonin syndrome

TREATMENT • Essential elements of therapy include: – Excluding alternate diagnoses (see above) – Seizure prophylaxis – Correcting metabolic and hemodynamic derangements – Treating symptoms such as anxiety and hallucinations – Managing complications (e.g., aspiration pneumonia and malnutrition) – Appropriate monitoring • Benzodiazepines bind to GABA receptors and are cross-tolerant with alcohol; they remain the cornerstone of treatment for AWS. They are effective at reducing anxiety, agitation, and the incidence of seizures; and they often reduce tachycardia and hypertension. They can also be dosed prophylactically, in a scheduled fashion, or in response to symptom severity.

The latter has been associated with decreased complications and lower doses of administered drug. • Propofol in intubated, mechanically ventilated patients produces results similar to those of benzodiazepines (e.g., anxiolysis, seizure prophylaxis, etc.). Patients receiving propofol rarely need additional benzodiazepines to treat agitation or seizures associated with AWS. • Other agents have been used, but none have completely replaced benzodiazepines: – Antipsychotics, such as haloperidol or quetiapine, may reduce agitation and hallucinations but may also reduce the seizure threshold. – Antiepileptics, such as carbamazepine, may decrease the development of seizures but have little effect on the other manifestations of AWS. – Intravenous infusion of ethanol can precipitate a metabolic acidosis. – Alternative sedatives, such as clonidine and dexmedetomidine, almost certainly reduce benzodiazepine requirements but provide no seizure prophylaxis. Dexmedetomidine reduces ICU delirium and may reduce delirium associated with AWS. • The Clinical Institute for Withdrawal Assessment (CIWA) provides a symptom-driven dosing scheme that calculates a score based upon signs and symptoms of withdrawal (e.g., tremor, sweats, delirium). Higher scores signify more severe withdrawal and would trigger administration of benzodiazepine. • Bed acuity: The appropriate level of monitoring for patients with AWS has never been defined. The frequent assessments required suggest that general ward care may be inadequate. Additionally, managing hemodynamic abnormalities requires active monitoring of hemodynamics, such as in a telemetry, step-down, or ICU unit. The presence of the following may necessitate ICU care: – Coexisting cardiac, pulmonary, or renal disease – Having a history of or being at high risk for DTs – Requiring propofol or a continuous infusion of sedatives to control symptoms during past admissions • Thiamine deficiency: Common in patients who abuse alcohol. Thiamine is critical in order to avoid Wernicke’s encephalopathy, and must be administered prior to initiating glucose or nutritional therapy. Further treatment should target specific nutritional deficiencies identified by serology.

REFERENCES

1. Tetrault JM, O’Connor PG. Substance abuse and withdrawal in the critical care setting. Crit Care Clin. 2008;24:767–788. 2. De Wit M, Jones DG, Sessler CN, et al. Alcohol-use disorders in the critically ill patient. Chest. 2010;138(4):994–1003. 3. Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348:1786–1795.

ADDITIONAL READING

• Spanagel R. Alcoholism: A systems approach from molecular physiology to addictive behavior. Physiol Rev. 2009;89:649–705.

• Sullivan JT, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: The revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Brit J Addict. 1989;84:1353–1357.

See Also (Topic, Algorithm, Electronic Media Element) • Alcohol abuse

CODES ICD9

291.81 Alcohol withdrawal ICD10 F10.239 Alcohol dependence with withdrawal, unspecified

CLINICAL PEARLS

• Cessation of receptor-mediated activity during alcohol abstinence is likely at the root of AWS. It may be that chronic exposure to ethanol decreases sensitivity of GABA receptors, and that cessation reduces GABA output, leading to a state of generalized CNS arousal. • Seizure may be an early symptom of AWS (“rum-fit”) which can occur as early as 2 hours after the last consumption of ethanol. • Alcohol-dependent, ambulatory patients may never exhibit AWS syndromes during the hospital stay. • Whenever AWS is suspected, thiamine should be given intravenously. The administration of glucose in thiamine deficiency can precipitate Wernicke’s encephalopathy.

ALCOHOLIC CARDIOMYOPATHY Christopher Wray, MD

BASICS DESCRIPTION

• Alcoholic cardiomyopathy (ACM) is classified as a non-ischemic, dilated cardiomyopathy (CM) that results from exposure to a myocardial toxin. • ACM shares common characteristics with all dilated CMs (depending on the clinical stage of the disease progression): – Dilated chambers – Diastolic dysfunction (asymptomatic stage) – Left ventricular dysfunction (symptomatic stage) – Left ventricular hypertrophy (asymptomatic stage; followed by wall thinning in symptomatic stage) • Diagnosis is clinically based upon a history of significant chronic alcohol exposure in conjunction with the exclusion of other causes of dilated CM. PHYSIOLOGY PRINCIPLES

• Epidemiology of ACM: – Second most common cause of dilated CM (4% of all CMs) – Prevalence in Western countries is variable, but ranges from 20% to 40% of all nonischemic dilated CMs. – Significantly more prevalent in men (approximately 15% prevalence in women) – The incidence of dilated CM is much higher in chronic alcoholics than in the total population. – The 5-year incidence ranges from 20% to 26% in chronic alcoholics. • Amount and duration of alcohol exposure: – Studies have demonstrated variability and a lack of a specific linear relationship between the amount and duration of alcohol exposure and the development of asymptomatic and symptomatic ACM (1,2,3). – Studies have shown changes in cardiac structure and function consistent with ACM in patients with a history of consuming >90 g/day of alcohol for >5 years (one drink contains approximately 12 g of alcohol). Studies in patients with symptomatic ACM have shown a history of longer durations of drinking (>10 years) (4,5). – Despite the correlation between chronic heavy drinking and the development of ACM, not all heavy drinkers will progress to ACM. – Although there may be other variables responsible for the occurrence of heart failure in alcoholics, the duration of heavy daily alcohol use is the most reliable predictor for the development of ACM. PHYSIOLOGY

• Myocardial wall tension is closely related to myocardial oxygen consumption. – Left ventricle wall tension (T) is a function of the change in pressure (ΔP), left ventricle radius (R), and left ventricle wall thickness (h). It can be described by the law of Laplace: T = (ΔP × R)/2h. – ΔP reflects the afterload that the left ventricle must pump against (directly related) – Radius is a function of preload (left ventricular end-diastolic volume) (directly related). – Wall thickness is a function of the number of myoctes (inversely related) – Although not intrinsically contained within the equation, heart rate also is a determinant of myocardial oxygen; it determines the number of times that tension needs to be generated. • The left ventricle is ellipsoid and facilitates low wall tension

DISEASE/PATHOPHYSIOLOGY

• The pathophysiology is not completely understood, despite a large number of studies. Animal studies have demonstrated characteristic histologic and cellular changes associated with chronic alcohol exposure, including (1): – Myocyte death – Intracellular organelle dysfunction – Interference of contractile protein function – Abnormalities of calcium homeostasis – Generation of reactive oxygen species (ROS) – Changes in neurohormonal systems (sympathetic, renin-angiotensin, natriuretic peptide) – Individual variations in the development of myocardial toxicity from alcohol suggest that other variables including genetic or environmental factors may play a role. • Clinical presentation: ACM presents in stages and can progress from asymptomatic to symptomatic. – Asymptomatic stage: Studies have demonstrated that in the early preclinical stage of ACM, LV remodeling occurs in the form of LV dilation (increased end-diastolic and systolic dimensions), increased LV mass, and LV hypertrophy (increased septal thickening). Echocardiographic studies have demonstrated that diastolic dysfunction (impaired early diastolic filling of the LV) appears to be an early feature of asymptomatic ACM, regardless of LV mass and the presence of hypertension. Early ACM is often associated with a normal LV ejection fraction (EF) (3,4,5,6). – Symptomatic stage: Characterized by progressive increases in LV dilation and LV mass, as well as the occurrence of systolic dysfunction with a decreased EF. Studies have demonstrated significantly greater LV end-diastolic and systolic dimensions in symptomatic ACM patients when compared to asymptomatic ACM patients (2,7). • Tension: Dilated cardiomyopathy results in a more spherical left ventricle with subsequent increases in wall stress (radius is increased). In the asymptomatic stage, the myocardial wall hypertrophies and can decrease wall tension. However, in symptomatic stages, wall thickness decreases with resultant increases in wall tension (and myocardial oxygen demand). • Diagnosis is clinically based upon having a history of significant alcohol consumption after ruling out other causes of dilated CM. – History: After excluding other causes of dilated CM, the most important factor for

diagnosis is a chronic history of heavy alcohol use. – Symptoms/physical exam: Signs and symptoms of heart failure may be noted in patients with symptomatic disease. – EKG abnormalities are common and include nonspecific ST and T wave changes, QT prolongation, and atrial arrhythmias including atrial fibrillation. – Echocardiography allows for a noninvasive delineation of the LV chamber size, diastolic function, and systolic function. – There are no specific pathologic or immunologic tests for the diagnosis of ACM. • Natural history and treatment – Although the amount of alcohol required to cause progression of asymptomatic ACM to overt heart failure appears variable, studies clearly show that decreases in systolic function are significantly related to the amount and duration of alcohol consumption (1). – Partial to complete regression of the pathologic cardiac changes associated with ACM may occur in some patients with abstinence alone. – LV function in ACM patients may improve with standard medical therapy for dilated CM (diuretics, cardiac glycosides, ACE inhibitors, and beta blockade), although no therapies specific for ACM have been studied or described. Despite improvements in the LV function, survival is not improved in patients who continue to drink. The most important factor impacting survival in symptomatic patients receiving medical therapy is abstinence from further drinking.

PERIOPERATIVE RELEVANCE

• Chronic alcoholism results in a significantly higher incidence of postoperative cardiac complications, hypoxemia, and infections. • The anesthesia provider should maintain an appropriate index of suspicion for the presence of ACM in patients with a history of chronic alcohol use. The presence of ACM can have worsened and even deleterious effects during the perioperative period. Even asymptomatic patients can have a limited cardiac reserve when exposed to severe perioperative stress that occurs with major surgery, trauma, or shock. Preoperative cardiac evaluation, including echocardiography, should be considered for risk-stratification and determination of the need for medical therapy for prospective surgical patients with a history of chronic alcohol use. • Alcoholics presenting for emergency surgery may be acutely intoxicated or at risk for alcohol withdrawal syndrome, both of which can adversely affect a patient with ACM (8).

REFERENCES

1. Piano MR. Alcoholic cardiomyopathy: Incidence, clinical characteristics, and pathophysiology. Chest. 2002;121:1638–1650. 2. Fernandez-Sola J. Diastolic function impairment in alcoholics. Alcohol Clin Exp Med. 2000;24:1830–1835. 3. Fauchier L. Comparison of long-term outcome of alcoholic and idiopathic dilated cardiomyopathy. Eur Heart J. 2000;21:306–314. 4. Kupari M. Left ventricular filling impairment in asymptomatic chronic alcoholics. Am J Cardiol. 1990;66:1473–1477.

5. Lazarevic AM. Early changes in left ventricular function in chronic asymptomatic alcoholics: Relation to the duration of heavy drinking. J Am Coll Cardiol. 2000;35:1599– 1606. 6. McKenna CJ. Alcohol consumption idiopathic dilated cardiomyopathy: A case control study. Am Heart J. 1998;135:833–837.

7. Mathews EC. Echocardiogrphic abnormalities in chronic alcoholics with and without overt congestive heart failure. Am J Cardio. 1981;47:570–578. 8. Spies C. Perioperative morbidity and mortality in chronic alcoholic patients. Alcohol Clin Exp Res. 2001;25:164S–170S.

ADDITIONAL READING

• Laonigro I. Alcohol abuse and heart failure. Eur J Heart Failure. 2009;11:453–462. • Spies CD. Effects of alcohol on the heart. Curr Opin Crit Care. 2001;7:337–343.

See Also (Topic, Algorithm, Electronic Media Element) • Congestive heart failure • Alcohol abuse

CODES ICD9 425.5 Alcoholic cardiomyopathy ICD10 I42.6 Alcoholic cardiomyopathy

CLINICAL PEARLS

• ACM is a type of dilated CM that is diagnosed clinically, based on a history of significant chronic alcohol exposure in conjunction with the exclusion of other causes of dilated CM. • The duration of heavy daily alcohol use is the most reliable predictor for the development of ACM. • The most important factor impacting survival in ACM patients is abstinence from further drinking; medical therapy does not improve survival in patients who continue to drink alcohol. • The presence of ACM in the surgical patient can have deleterious effects; the anesthesia provider should maintain an appropriate index of suspicion for the presence of ACM in patients with a history of chronic alcohol use.

ALDOSTERONE Joe C. Hong, MD

BASICS DESCRIPTION

• Aldosterone is a steroid hormone in the mineralocorticoid family that plays a vital role in the maintenance of intravascular volume status and sodium balance. • Aldosterone is synthesized and secreted by the zona glomerulosa of the adrenal cortex in response to low intravascular volume, decreased renal perfusion, hyperkalemia, and acidosis. • Disease states include Addison disease (hypoaldosteronism) and Conn syndrome (hyperaldosteronism). PHYSIOLOGY PRINCIPLES

• Aldosterone is synthesized from cholesterol within the adrenal cortex by a series of steroidogenic reactions catalyzed by enzymes of the cytochrome p450 family. It is a steroid hormone that exerts its action by binding to an intracellular cytoplasmic receptor. This bound complex enters the cell nucleus and stimulates DNA transcription, resulting in protein production that mediates the ultimate effects of aldosterone. • Renin–angiotensin system (RAS) regulation: Aldosterone secretion is regulated primarily by RAS via the following mechanism: – Intravascular volume depletion triggers a decrease in renal perfusion pressure. – Renin is secreted by the juxtaglomerular cells of the afferent arteriole in response to this decrease in renal perfusion pressure. – Renin catalyzes the conversion of angiotensinogen to angiotensin I in plasma. – Angiotensin-converting enzyme (ACE) catalyzes the conversion of angiotensin I to angiotensin II, primarily in the lungs. – Angiotensin II stimulates the synthesis and secretion of aldosterone. • Adrenocorticotropic hormone (ACTH): Aldosterone is also under tonic control by ACTH (secreted by the anterior pituitary gland). • Aldosterone hormone regulates volume and blood pressure via: – Binding to mineralocorticoid receptors located in the principal cells of nephrons. This upregulates sodium/potassium pumps with resultant sodium and water reabsorption and potassium sercetion by the distal tubules and collecting ducts. The net effect is the restoration of intravascular volume and blood pressure. – Acting on alpha-intercalated cells of the late distal tubule and collecting duct, resulting in increased renal hydrogen ion secretion. ANATOMY

• Aldosterone is produced by cells within the zona glomerulosa of the adrenal cortex. • The adrenal gland is composed of the inner medulla which produces catecholamines and the

outer cortex which is divided into 3 histologic zones. Going from outside and moving inwards: – The outermost zona glomerulosa is the source of aldosterone production. – Just beneath is the zona fasciculata, the source of glucocorticoid production. – The inner-most layer of the cortex is the zona reticularis, responsible for the production of androgens.

DISEASE/PATHOPHYSIOLOGY

• Primary adrenocortical insufficiency (Addison disease)—a hypoaldosterone state: – Most common cause is autoimmune destruction of the adrenal cortex, resulting in acute adrenal crisis (1). Other causes of adrenocortical insufficiency include metastatic disease to the adrenal cortex, adrenal hemorrhage, infection of the adrenal gland (tuberculosis, opportunistic infections with HIV, fungemia), and amyloid infiltration. – Characterized by elevated ACTH levels but decreased levels of glucocorticoids and mineralocorticoids – Clinical features are related to the adrenocortical hormone deficiency. Hypoglycemia is caused by cortisol deficiency. Hypotension, hyperkalemia, metabolic acidosis, and volume contraction are caused by aldosterone deficiency. Hyperpigmentation is caused by elevated ACTH secretion. Other signs and symptoms include weakness, fatigue, lethargy, anorexia, nausea, abdominal pain, prerenal azotemia, hypercalcemia, convulsions, fever, and syncope. – Treatment: Replacement of glucocorticoids (hydrocortisone, prednisone, methylprednisolone) and mineralocorticoids (fludrocortisone) • Secondary adrenocortical insufficiency is caused by decreased ACTH secretion, resulting primarily in a glucocorticoid deficiency. Mineralocorticoid deficiency is also seen but to a lesser degree. – Most common cause of secondary adrenocortical insufficiency is sudden withdrawal of long-term corticosteroid therapy (2). Other causes include pituitary tumor, pituitary surgery or radiation, postpartum hypopituitarism (Sheehan syndrome), and sarcoid infiltration of the pituitary gland. – Chronic corticosteroid therapy suppresses the hypothalamus and anterior pituitary, resulting in decreased production of corticotropin-releasing hormone (CRH) and ACTH, respectively. Decreased levels of CRH and ACTH cause atrophy of the zona fasciculata, resulting in glucocorticoid deficiency. During times of physiologic stress, the patient is unable to acutely increase cortisol production, resulting in acute secondary adrenocortical deficiency. • Primary hyperaldosteronism is caused by aldosterone-secreting tumors. – Conn syndrome (aldosterone-secreting adrenocortical adenoma) is the most common cause. Bilateral adrenal hyperplasia occurs less commonly. – Characterized by hypertension, hypokalemia, metabolic alkalosis, and a low renin state. Other signs and symptoms include tetany, polyuria, and an inability to concentrate urine. – Primary hyperaldosteronism may be present in 0.5–1% of patients with hypertension (3). – Treatment: Medically by spironolactone (aldosterone receptor antagonist), surgically with adrenalectomy

PERIOPERATIVE RELEVANCE

• Hypoaldosterone states: – Patients with adrenocortical insufficiency should continue their mineralocorticoid and glucocorticoid replacement therapy up until their time of surgery. Clinical features of overt hypoaldosteronism include hyperkalemia, hyponatremia, acidosis, and myocardial conduction defects. Administration of mineralocorticoids (fludrocortisone 0.05–0.1 mg/d) should occur preoperatively (1). Doses must be carefully titrated to avoid hypertension. – Additional perioperative stress dose of glucocorticoids may be necessary since these patients may not be able to mount an adequate stress response. The traditional recommendation is 200 mg hydrocortisone per 70 kg body weight per day. However, smaller doses of 100 mg per 70 kg body weight per day have been used with success (2). – The amount of perioperative hydrocortisone is based on the anticipated stress of the procedure. The relative degree of trauma and depth of anesthesia should be considered. • Hyperaldosterone states: – Patients presenting for elective surgery should be medically optimized in terms of their adrenocortical disorder. Preoperative EKG, glucose, and serum electrolytes (particularly sodium and potassium) should be checked. Volume status and blood pressure should be optimized. – Primary aldosteronism (Conn syndrome) should be suspected in patients who present with concurrent hypertension and hypokalemia, severe refractory hypertension, adrenal incidentaloma and hypertension, or onset of hypertension at a young age. – Antihypertensive medications (e.g., spironolactone) should be maintained up to the time of surgery. Careful cardiac assessment is necessary because these patients have increased cardiac comorbidity. Serum sodium and especially serum potassium should be checked prior to surgery. Hypokalemia is common. Severely hypokalemic patients should have their potassium replaced preoperatively.

REFERENCES

1. Dorin RI, Qualis CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med. 2003;139:194–204. 2. Symreng T, Karlberg BE, Kagedal B, et al. Physiological cortisol substitution of long-term steroid-treated patients undergoing major surgery. Br J Anaesth. 1981;53:949–954. 3. Young WF Jr. Adrenal causes of hypertension: Pheochromocytoma and primary aldosteronism. Rev Endocr Metab Disord. 2007;8:309–320.

ADDITIONAL READING

• Graham GW, Unger BP, Coursin DB. Perioperative management of selected endocrine disorders. Int Anesthesiol Clin. 2000;38:31–67. • Lampe GH, Roizen MF. Anesthesia for patients with abnormal function of the adrenal cortex. Anesthesiol Clin North Am. 1987;5:245–268. • Udelsman R, Ramp J, Gallucci WT, et al. Adaptation during surgical stress: A reevaluation of the role of glucocorticoids. J Clin Invest. 1986;77:1377–1381.

See Also (Topic, Algorithm, Electronic Media Element) • Cortisol • Acute adrenal insufficiency

CLINICAL PEARLS

• Patients with adrenocortical insufficiency have deficiencies in both mineralocorticoids and glucocorticoids. Hydrocortisone has both glucocorticoid and mineralocorticoid activity. Therefore, it is an ideal agent to use for the management of adrenocortical insufficiency. • Patients with aldosterone deficiency should continue their fludrocortisone up until the time of surgery. Hypokalemic acidosis or hypovolemia must be treated preoperatively. Supplementation of mineralocorticoids (fludrocortisone 0.05–0.1 mg/d) should occur preoperatively. Doses must be carefully titrated to avoid hypertension. • Primary hyperaldosteronism (Conn syndrome) should be suspected in patients who present with concurrent hypertension and hypokalemia, severe refractory hypertension, adrenal incidentaloma and hypertension, or onset of hypertension at a young age.

ALVEOLAR ARTERIAL GRADIENT AND RATIO Sharanya Nama, MD Michael Mangione, MD

BASICS DESCRIPTION

• The alveolar–arterial gradient and ratio provide a useful, objective means to determine how effectively oxygen from the alveolus moves into the pulmonary circulation. It aids with: – Identifying increases in venous admixtures, even in the presence of increased inspired oxygen concentrations – Monitoring improvement or worsening of the venous admixture – Assessing effectiveness of treatment and interventions – Differentiating between causes of hypoxia (impaired uptake vs. decreased alveolar oxygen availability) PHYSIOLOGY PRINCIPLES

• Definitions: – PAO2 = alveolar PO2. It is determined by the alveolar gas equation and is calculated as follows: PAO2 = [FiO2 × (Patm – PH2O) – (PaCO2/0.8)]; measured in units of mm Hg.

– PaO2 = arterial PO2. It is determined by direct arterial blood gas values and is measured

in units of mm Hg. Small amounts of oxygen are dissolved in the plasma, which are in equilibrium with the oxygen bound to hemoglobin. Thus, a decrease in arterial oxygen content would reflect a decrease in hemoglobin binding and decreased oxygen saturation. • A-a gradient: The difference between the alveolar and arterial partial pressure of oxygen – Normal adult values in nonsmokers are <15 mm Hg on room air (FiO2 = 0.21) (1). For example, a patient with a PAO2 = 100 mm Hg and a PaO2 = 93 mm Hg has an A-a

gradient of 7. – Higher FIO2 values result in an increased A-a gradient. For every 10% increase in FiO2,

the A-a gradient increases by 5–7 mm Hg. This effect is caused by the loss of regional hypoxic vasoconstriction in the lungs (2). • Advancing age: Results in a steady rise in the A-a gradient (3); PaO2 predicted = 109 – (0.4 × age in years). For example, a 60-year-old breathing room air would have an average A-a gradient of 14 mm Hg. In comparison, someone below the age of 40 would have a gradient of 7 mm Hg (3). • A-a gradient: The arterial oxygen concentration divided by the alveolar oxygen concentration. This value is useful in predicting the change in PaO2 when the FIO2 also

changes since it is relatively unaffected by varying oxygen levels (4). – The normal a/A PO2 ratio is 0.74–0.77 when breathing room air (FIO2 = 0.21). It only

increases to 0.80–0.82 when breathing 100% oxygen (5). • Physiologic shunting and normal venous admixture – The thebesian veins drain venous blood from all 4 walls of the myocardium (mostly right atrium) and empty into the left atrium. – Deep bronchial veins drain venous blood from the bronchi and roots of the lungs and empty into the pulmonary veins (deoxygenated blood that returns to the left atrium). – Venous blood from these areas does not enter the pulmonary circulation; instead, it returns to the systemic circulation without becoming oxygenated. This accounts for a total of 2–5% of cardiac output, and the mixing of oxygenated and deoxygenated blood is known as venous admixture. – This normal venous admixture accounts for the 10–15 mm Hg A-a gradient and the 0.74– 0.77 a/A ratio that is considered normal. • Hypoxic pulmonary vasoconstriction describes a physiologic phenomenon in which the pulmonary arterioles constrict in the presence of low oxygen tension in the alveoli (e.g., atelectasis). – This vessel constriction results in re-directing blood flow to well-oxygenated lung units and away from poorly oxygenated lung units to ultimately improve ventilation-perfusion (V/Q) matching. – When a patient is given supplemental oxygen, more alveoli become well-oxygenated; however, it also, in turn, decreases hypoxic vasoconstriction. – This increase in V/Q mismatch leads to more deoxygenated blood entering the systemic circulatory system and in turn increases the A-a gradient.

ANATOMY

• Alveolus – Air sac that is lined with a thin membrane consisting of epithelium with collagen and elastin – Gas exchange occurs across this membrane where gases move down a concentration gradient between alveolus and pulmonary capillary. • Pulmonary circulation – Consists of blood vessels that carry deoxygenated blood to the site of gas exchange • Pulmonary capillaries – Consists of a single layer of squamous epithelium surrounded by a basement membrane – Gases must diffuse across these layers to enter circulation.

DISEASE/PATHOPHYSIOLOGY

• Hypoxia with increased A-a gradient and a/A ratio: Results from an increase in the venous admixture secondary to blood passing through the lung without being properly oxygenated (in addition to the physiologic admixture). Examples of this include: – V/Q mismatch: Discrepancy between the alveolar ventilation and capillary perfusion – Pulmonary shunt: Perfusion of the alveolar unit without ventilation, due to pathologic processes. Atelectasis describes alveolar deflation or fluid collection of the alveolar unit. Deflation can result from airway obstruction, mucus or blood plugging, inadequate tidal volumes due to pain, or positioning changes; other causes include endobronchial intubation, pneumothorax, collapse of emphysematous blebs, and one lung ventilation (6).

Fluid collection can result from pulmonary edema, pneumonia, or adult respiratory distress syndrome (ARDS). – Intracardiac shunt: Venous blood is diverted from the pulmonary circulation directly into the systemic circulation. Examples include atrial or septal defects, pulmonary atrioventricular (AV) malformations, and cyanotic congenital heart disease. – Diffusion defects: Observed when the alveolar oxygen and carbon dioxide tensions are normal, but oxygen uptake by the alveolar capillaries is abnormal or impaired. Examples include pulmonary fibrosis, interstitial lung inflammation, and interstitial edema. • Hypoxia with normal A-a gradient or a/A ratio: Can be seen in situations where the alveolar oxygen (or carbon dioxide) is affected, but oxygen uptake by the capillaries is not impaired. The decreased arterial oxygen concentration reflects the decreased alveolar concentration. – Hypoxic delivery: Anesthesia machine or ventilator malfunction, or high altitude – Hypoventilation: Respiratory depression from drugs, stroke in the pontine area, respiratory muscle fatigue (such as myasthenia gravis), or obesity–hypoventilation syndrome. The increase in carbon dioxide decreases the oxygen partial pressure (concentration) within the alveoli.

PERIOPERATIVE RELEVANCE

• Assessing the A-a gradient or ratio can: – Differentiate between hypoxia secondary to low alveolar oxygen tension or due to increase in venous admixture from underlying pathology – Provide an objective means to trend venous admixtures and, hence, assess pulmonary processes – Assess the effectiveness of treatment and interventions such as positive end expiratory pressures (PEEP) – The A-a gradient is directly proportional to shunt while being inversely proportional to the mixed venous oxygen tension. – Pulse oximetry only provides an assessment of hemoglobin binding. As oxygen saturation reaches the high 90’s, it can no longer be a reliable marker for arterial oxygen content. Therefore, pulse oximetry cannot aid with assessing the severity of the A-a gradient in a given disease state. For example, patients A and B both have ARDS. Patient A is on 50% FiO2; his PAO2 is 350 mm Hg and his PaO2 is 120 mm Hg resulting in an A-a gradient of 230 mm Hg and SpO2 of 99%. Patient B also has ARDS and is on 50% FiO2; his PAO2 is

350 mm Hg and his PaO2 is 320 mm Hg resulting in an A-a gradient of 30 and SpO2 of

99%. Therefore, it is not possible to assess the status of the underlying pathology with higher supplemental oxygen based on oxygen saturation alone; one must obtain a blood gas and calculate the A-a gradient. – Assessing a/A ratio: In patients receiving higher or changing FiO2, the ratio can provide a more consistent value that allows for comparison. Additionally, it has been shown to be more reliable than the A-a gradient in hemodynamically stable patients (7). – Perioperative conditions: The functional residual capacity (FRC) is decreased by several factors that ultimately increase the venous admixture, A-a gradient, and a/A ratio. General anesthesia

Positioning (supine, prone or steep Trendelenburg position) Surgical procedure (laparoscopy, abdominal retractors) Patient (obesity, pregnancy, ascites) (8) • Maneuvers and techniques to improve lung oxygenation can be assessed objectively by calculating the A-a gradient or a/A ratio. – Pulmonary edema may be treated by optimizing preload (diuresis, venodilators) and afterload (vasodilators) to increase inotropy. – Ventilator adjustments such as PEEP, adjusting rate, volume, I:E ratios, and lung recruitment maneuvers – Surgical maneuvers such as decreasing the insufflation pressures during laparoscopy or retractor tension – Positioning changes: Elevating the head of the bed can shift the abdominal contents away from the diaphragm and allow for increased lung expansion.

EQUATIONS

• A-a gradient = PAO2 – PaO2 • a/A ratio = PaO2/PAO2

• PAO2 = [FiO2 × (Patm – PH2O) – (PaCO2/0.8)]

• On room air (21%) at sea level, a simplified version: A-a gradient = [(150 – 5)/4(PCO2)] – PaO2

• Normal A-a gradient ∼ (age +10)/4

REFERENCES

1. Mellemgaard K. The alveolar–arterial oxygen difference: Its size and components in normal man. Acta Physiol Scand. 1966;67(1):10–20. 2. Williams AJ. ABC of oxygen: Assessing and interpreting arterial blood gases and acid-base balance. BMJ. 1998;317(7167):1213–1216. 3. Kanber GJ, King FW, Eshchar YR, et al. The alveolar–arterial oxygen gradient in young and elderly men during air and oxygen breathing. Am Rev Respir Dis. 1968;97(3):376–381. 4. Peris LV, Boix JH, Salom JV, et al. Clinical use of the arterial/alveolar oxygen tension ratio. Crit Care Med. 1983;11(11):888–891. 5. Gilbert R, Kreighley JF. The arterial/alveolar oxygen tension ratio: An index of gas exchange applicable to varying inspired oxygen concentrations. Am Rev Respir Dis. 1974;109:142–145. 6. Thurlbeck WM, Müller NL. Emphysema: Definition, imaging, and quantification. Am J Roentgenol. 1994;163:1017–1025. 7. Gilbert R, Auchincloss JH Jr, Kuppinger M, et al. Stability of the arterial/alveolar oxygen partial pressure ratio: Effects of low ventilation/perfusion regions. Crit Care Med. 1979;7(6):267–272. 8. Woodring JH, Reed JC. Types and mechanisms of pulmonary atelectasis. J Thorac Imaging. 1996;11:92–108.

ADDITIONAL READING

• Rodríguez-Roisin R, Roca J. Mechanisms of hypoxemia. Intensive Care Med. 2005;31(8):1017–1019.

See Also (Topic, Algorithm, Electronic Media Element) • Functional residual capacity • Mixed venous oxygen saturation • Oxygen carrying capacity • Pulmonary ventilation perfusion matching • One lung ventilation • Hypoxia, intraoperatively • PaO2

CLINICAL PEARLS

• Pulse oximetry in the presence of a high FIO2 may not be an adequate marker of pulmonary pathology as reflected by the A-a gradient. • Hypoxemia caused by physiologic shunt may not be responsive to increased FiO2.

ALVEOLI

Megan Freestone-Bernd, MD Mary E. McAlevy, MD

BASICS DESCRIPTION

Alveoli are the thin-walled, sac-like, terminal dilations of the respiratory bronchioles, alveolar ducts, and alveolar sacs. They serve as the functional unit for gas exchange with pulmonary capillaries. • The adult lung contains approximately 300 million alveoli. • The combined maximal volume is approximately 5–6 L. • Each alveoli is surrounded by capillaries. • The combined surface area ranges from 50 to 100 m2. PHYSIOLOGY PRINCIPLES

• Alveolar walls: Comprised of a thin epithelial layer that consists of alveolar type I and alveolar type II cells. – Alveolar type I cells are squamous epithelial cells and cover approximately 80% of the alveolar surface. They are highly differentiated and very susceptible to injury. If the type I cell is damaged, the type II cells replicate and modify to form new type I cells. – Alveolar type II cells are cuboidal epithelial cells that synthesize and secrete the fluid layer (surfactant) that lines the alveoli. The type II alveolar cells also control local electrolyte balance and lymphatic cell functions. – Alveolar type III cells are alveolar macrophages and are an important element of lung defense. They are part of the lung inflammatory response and ingest foreign materials within the alveoli. • Alveoli size: – Individual alveoli range from about 75 to 300 μm. – Surface tension: Describes the force exhibited by water molecules in the alveoli towards one another. Water has a greater attraction to each other than to air, causing the alveoli to tend towards collapse. For example, as alveoli become smaller, water molecules come closer together, and surface tension is increased. As alveoli increase in size, water molecules are further apart, and surface tension is decreased. – Law of Laplace: The pressure required to keep an alveolus open is directly proportional to the surface tension within the alveolus and indirectly proportional to the alveolar radius. P = 2T/r, where P = pressure, T = surface tension, and r = radius. – Surfactant: A phospholipoprotein that contains both a hydrophilic and hydrophobic region that lines the alveoli. It adsorbs to the alveolar air–water interface and decreases surface tension by decreasing the interaction between water molecules. Thus, surfactants function to stabilize the alveoli; the tendency for small alveoli to collapse would result in emptying into larger alveoli.

– Pleural pressure: Varies throughout the lung. At the apices, the pleural pressure is the most negative; therefore, the alveoli are more expanded than at the bases of the lungs. • Gas exchange across the alveoli is determined by the partial pressure difference across the membrane and the solubility of the gas. The alveoli epithelium and basement membrane provide minimal hindrance and are optimal for this function. Carbon dioxide diffuses 20 times as rapidly as oxygen; oxygen diffuses twice as rapidly as nitrogen.

ANATOMY

• Alveoli are the terminal branches in the pulmonary tree. • The pulmonary tree begins with the trachea which then branches into the right and left mainstem bronchi. These bronchi then further divide into bronchioles, alveolar ducts, and alveolar sacs. • The lungs receive blood from the pulmonary and bronchial circulation. – Pulmonary circulation: Deoxygenated blood flows from the right ventricles into the pulmonary arteries which branch along with the bronchial tree until they reach the respiratory bronchioles. At this point, they form a dense capillary network that provides a very large area for gas exchange. Oxygenated blood returns to the left atrium via the pulmonary veins. – Bronchial circulation: The blood is supplied from the aortic arch, the thoracic aorta, and the intercostals arteries. It feeds the trachea, bronchi, and bronchioles as well as the intrapulmonary nerves, ganglia, and interstitial lung tissue. It drains into the right atrium as deoxygenated blood. • Zones: Blood flow through the lungs is dependent upon gravity as well as the relative pressures in each area. These pressures include the pulmonary artery pressure (Ppa), the pulmonary venous pressure (Ppv), and the alveolar pressure (PA). Three zones have been described: – Zone 1: Located at the lung apex, the perfusion pressure is about equal to the alveolar pressure so blood flow is low (PA > Ppa > Ppv). Zone 1 therefore has ventilation without perfusion and is essentially dead space. – Zone 2: The middle zone where the perfusion pressure is greater than the alveolar pressure so blood flows easily (Ppa > PA > Ppv). Zone 2 is the area of “best matched” ventilation and perfusion; it also contains the most number of alveoli. – Zone 3: Located at the lung base, where the perfusion pressure is much greater than the alveolar pressure so blood flow is high (Ppa > Ppv > PA). Zone 3 has very good perfusion, but less ventilation which results in shunting.

DISEASE/PATHOPHYSIOLOGY

• Atelectasis is the term used to describe “collapsed” alveoli; the term can be applied to a single unit, lobe, or the entire right or left lung. Blood that perfuses the collapsed cannot pick up oxygen or offload carbon dioxide, resulting in pulmonary shunting. As the number of atelectatic units increases, it is less likely that the blood will be oxygenated by a proximal or distal unit before returning to the left atrium. • Neonatal respiratory distress syndrome (RDS) can be present in premature infants due to a lack of surfactant. The increase in surface tension results in alveolar collapse (atelectasis), with resultant hypoxemia, decreased compliance, and problems re-inflating the lungs.

Surfactant may be present by week 24 and is almost always present by gestational week 35. If there are mature levels of surfactant, the amniotic fluid will have a lecithin:sphingomyelin ratio >2:1. Corticosteroids may be given to encourage formation of surfactant in cases of pre-term labor. • Emphysema is a disease where alveoli undergo destruction and elastic recoil is decreased; this results in increased alveolar size. It is most commonly caused by smoking, but can also result from alpha-1 antitrypsin deficiency. Bronchoalveolar lavage will demonstrate the presence of neutrophils; these cells cause damage to the lung parenchyma by secretion of proteolytic enzymes. Alveolar damage decreases gas exchange area, leading to hypoxemia, hypercarbia, and chronic dyspnea. • Pulmonary fibrosis describes thickening of the alveolar wall; this impairs the diffusing capacity of gas through the alveoli. • Cystic fibrosis is a genetic disease of the epithelial chloride channel to open normally in response to cyclic AMP. This defect decreases water passage across the epithelial membrane, leading to abnormally thick mucous in the airways. Mucus can obstruct small airways (plugs) and result in frequent pulmonary infections. • Aspiration pneumonitis of acidic solutions may lead to destruction of surfactant-producing type II pneumocytes and the capillary endothelium. Damage to these cells may lead to atelectasis and leakage of fluid into the lungs. Arterial hypoxia may ensue, which leads to pulmonary vasoconstriction with associated pulmonary hypertension, as well as tachypnea and bronchospasm. • Congestive heart failure describes cardiac dysfunction with “back-up” into the pulmonary vasculature (increased capillary pressure). This initially causes dilation and recruitment of pulmonary capillaries making it more difficult for alveoli to expand (results in decreased lung compliance, and increased work of breathing). As capillary pressures increase, fluid will eventually extravasate into the interstitial space around the alveoli. With further increases in pressure, fluid will eventually enter into the alveoli. • Acute respiratory distress syndrome (ARDS) is defined as severe hypoxemia, diffuse shadows on CXR, low pulmonary compliance, and pulmonary edema not from left-sided heart failure. The lung parenchyma is severely damaged due to chemical mediators and fibroblasts. There is an inflow of protein-rich fluid into the alveoli due to increased permeability of the alveolar capillary membranes. Diseases that may precipitate ARDS include: septic shock, aspiration of gastric contents, pneumonia, pulmonary contusions, near drowning, severe trauma with associated shock, and inhalation of toxic gases or smoke.

PERIOPERATIVE RELEVANCE

Positive end-expiratory pressure (PEEP) is effective in improving arterial oxygenation and should be used when indicated. PEEP helps prevent alveolar collapse at the end of expiration and in doing so may decrease the shear stress associated with the opening and closing of alveoli with mechanical ventilation. PEEP also helps ventilation-to-perfusion matching as well as decreasing right-to-left intrapulmonary shunt. Because PEEP recruits alveoli that were previously collapsed, it helps to increase lung volumes and functional residual capacity (FRC). However, by increasing the intrathoracic pressure, it can decrease preload to the right atrium and decrease cardiac output.

EQUATIONS

Law of Laplace: P = 2T/r, where P = pressure, T = surface tension, and r = radius

REFERENCES

1. Daniels CB, Orgeig S. Pulmonary surfactant: The key to the evolution of air breathing. News Physiol Sci. 2003;18:151–157. 2. Smetana GW. Preoperative pulmonary evaluation. N Engl J Med. 1999;340:937–944. 3. Staton GW, Ingram RH. Pulmonary edema. Sci Am Med. 1997:1–10.

4. Tobin MJ. Culmination of an era in research on the acute respiratory distress syndrome. N Engl J Med. 2000;342:1360–1361. See Also (Topic, Algorithm, Electronic Media Element) • Atelectasis • Surfactant • Pulmonary ventilation and perfusion matching • Acute respiratory distress syndrome • Cardiogenic pulmonary edema • Noncardiogenic pulmonary edema

CLINICAL PEARLS

• During normal spontaneous ventilation, the alveolar-to-dead space ventilation ratio is 1:1. During mechanical ventilation under anesthesia, dependent lung regions will have alveolar collapse, and ventilation is preferably distributed to the nondependent areas (ratio changes to 1:2). These alveoli may become over-aerated if high levels of PEEP are used.

AMNIOTIC FLUID EMBOLISM Kanishka Monis, MD Poovendran Saththasivam, MD

BASICS DESCRIPTION

• Amniotic fluid embolism (AFE) is a rare, but often fatal, obstetric emergency. It was first described by Dr. Meyer in 1926. • Entry of amniotic fluid into the maternal circulation via the placenta can occur during pregnancy or in the immediate postpartum period. • Amniotic fluid contains: – Epithelial squamous cells from the fetal skin – Mucin which originates from meconium – Lanugo – Fat from vernix caseosa EPIDEMIOLOGY Prevalence

Hard to assess due to a lack of sensitive and specific diagnostic studies; however, estimated to be 7.7 in 100,000 births in the US. Morbidity

Neurologic impairment is seen in 61% of women and 50% of infants who survive AFE Mortality

• AFE is the fifth most common cause of maternal mortality in the world. • Maternal mortality approaches 60%. • Fetal mortality rate is around 21%.

ETIOLOGY/RISK FACTORS

• Advanced maternal age • Tumultuous labor • Placental abnormalities (placenta previa, abruptio placentae) • Operative deliveries (Cesarean section, assisted vacuum deliveries, forceps-assisted deliveries) • Eclampsia • Polyhydramnios • Cervical lacerations • Uterine rupture • Medical induction of labor

PHYSIOLOGY/PATHOPHYSIOLOGY

• 4 main physiologic alterations in AFE: – Maternal cardiovascular collapse – Coagulopathy – Respiratory distress – Altered mental status • Amniotic fluid entry. It is hypothesized that the combination of breaches to the maternal circulation along with increased intrauterine pressures can facilitate entry of amniotic fluid into the circulation. – Breaches in the physical barrier can occur at the level of endocervical veins, the placental attachement site, or at uterine trauma sites. – Increased intrauterine pressure (and incidence of AFE) is seen in conditions such as polyhydramnios, placenta previa, placenta abruption, operative deliveries, uterine rupture, and cervical lacerations. • Maternal cardio-respiratory collapse may result from the following mechanisms – Mechanical obstruction of the pulmonary arteries (dead space; ventilation, but no perfusion) Amniotic debris obstructs the pulmonary artery leading to pulmonary hypertension and acute right ventricular failure. The increased right ventricular afterload results in a dilated right ventricle and deviation of the inter-ventricular septum. This can impair left ventricular filling with resultant left ventricular failure. Transesophageal echocardiography supports these findings. – Immunologic responses. Generalized constriction of the pulmonary vasculature results in relative shifting of blood flow to areas of lower ventilation from higher ventilation (shunt; perfusion, but inadequate ventilation). The complement cascade is activated and the subsequent immunologic reactions can result in pulmonary vasoconstriction. Of note, low levels of complement (C3 and C4) have been observed in some parturients with AFE Endothelin has also been found in amniotic fluid and can lead to pulmonary vasoconstriction Other humoral mediators, such as histamine, serotonin, prostaglandins, and leukotrienes have been linked to the onset of shock, myocardial depression, and disseminated intravascular coagulopathy • Coagulopathy associated with AFE is mainly related to consumption. – Amniotic fluid contains tissue factors that activate the extrinsic pathway by binding to factor VII. – Amniotic fluid is also found to have a thromboplastin-like effect and factor X activating property.

PREVENTATIVE MEASURES

• Avoid trauma to the uterus during insertion of a pressure catheter or during artificial rupture of the membrane. • During a Cesarean section, incision on the placenta should be avoided. • Excessively strong and frequent uterine contractions, as may be seen with oxytocin administration, should be minimized.

PREOPERATIVE ASSESSMENT • A diagnosis of exclusion, based on clinical presentation, or postmortem findings • AFE usually occurs during the intrapartum period or immediately postpartum. • Symptoms: – Sudden breathlessness – Nausea/vomiting – Dizziness – Chest pain – Panic attack – Pin and needle sensation in fingers – Bleeding • Signs: – Hypotension – Respiratory distress – Cyanosis – Fetal distress • Diagnostic tests and imaging: – Nonspecific tests include CBC, coagulation profile, ABG, BUN, and cardiac enzymes. – EKG may shown an acute right ventricular strain pattern. – Chest radiograph may indicate a dilated right heart, prominent pulmonary arteries, and pulmonary edema. – Transesophageal echocardiography may reveal pulmonary hypertension, acute right ventricular failure with leftward deviation of the inter-ventricular and inter-atrial septum and severe tricuspid regurgitation. – Serum markers for AFE: Specific markers include zinc coproporphyrin (a component of meconium) and sialyl Tn antigen (a component of meconium and amniotic fluid). Nonspecific serum markers include serum tryptase (marker of mast cell degranulation) and complement factors. The presence of fetal squamous cells in the maternal circulation is suggestive but not diagnostic of AFE.

DIFFERENTIAL DIAGNOSIS

• Pulmonary thromboembolism • Air embolism • Myocardial infarction/cardiac arrhythmia • Aortic dissection • Anesthetic-related complication (total or high spinal block) • Allergic anaphylaxis • Abruptio placentae • Uterine rupture • Sepsis

TREATMENT • Treatment is mainly supportive care aimed at the: – Correction of hypoxia and maintenance of oxygenation: Administer oxygen immediately with a goal of SpO2 >90%

Ventilate by face mask, Ambu bag, or endotracheal intubation – Correction of hypotension and maintenance of cardiac output: Initiate cardiopulmonary resuscitation (CPR) immediately Rapid restoration of preload using crystalloid solution Inotropic support in cases where hypotension is refractory to fluid therapy Maintain a systolic blood pressure >90 mm Hg – Correction of coagulopathy: Transfuse packed red blood cells to maintain adequate blood oxygen-carrying capacity and oxygen delivery to tissues. Fresh frozen plasma, platelet, and cryoprecipitate can be transfused to correct specific laboratory coagulation derangements. Recombinant activated factor VIIa has been used to manage severe DIC not responding to blood products transfusion • Pulmonary hypertension may be treated with inhaled nitric oxide, prostacyclin, and sildenafil.

FOLLOW-UP • Risk of recurrence in the subsequent pregnancy is unknown. • Neurologic disability in the mother and infant remains a common complication following AFE.

REFERENCES

1. Abenhaim HA, Azoulay L, Kramer MS, et al. Incidence and risk factors of amniotic fluid embolisms: A population-based study on 3 million births in the United States. Am J Obstet Gynecol. 2008;199(1):49.e1–49.e8. Conde-Agudelo A, Romero R. Amniotic fluid embolism: An evidence-based review. Am J Obstet Gynecol. 2009;201(5):445.e1–445.e13. Erratum in: Am J Obstet Gynecol. 2010;202(1):92. 2. Harboe T, Benson MD, Oi H, et al. Cardiopulmonary distress during obstetrical anaesthesia: Attempts to diagnose amniotic fluid embolism in a case series of suspected allergic anaphylaxis. Acta Anaesthesiol Scand. 2006;50(3):324–330. 3. Kane SK. Historical perspective of amniotic fluid embolism. Int Anesthesiol Clin. 2005;43(4):99–108. 4. Moore J, Baldisseri MR. Amniotic fluid embolism. Crit Care Med. 2005;33(Suppl 10):S279– S285. See Also (Topic, Algorithm, Electronic Media Element) • Venous air embolism

• Dead space

CODES ICD9

• 673.10 Amniotic fluid embolism, unspecified as to episode of care or not applicable • 673.11 Amniotic fluid embolism, delivered, with or without mention of antepartum condition • 673.12 Amniotic fluid embolism, delivered, with mention of postpartum complication ICD10

• O88.111 Amniotic fluid embolism in pregnancy, first trimester • O88.112 Amniotic fluid embolism in pregnancy, second trimester • O88.119 Amniotic fluid embolism in pregnancy, unspecified trimester

CLINICAL PEARLS

• Due to significant morbidity and mortality, a high index of suspicion is warranted. • Suspect AFE when the laboring patient complains of sudden breathlessness, or incurs hypotension or cardiac arrest. • Rule out pulmonary thromboembolism and anesthetic complications (e.g., high spinal) in the parturient suspected of AFE. • The mainstay of therapy is to support oxygenation and circulation to prevent end-organ damage with severe debilitating neurologic sequelae. • Parturients have improved prognosis when AFE is diagnosed early and aggressive treatment is administered.

AMYLOIDOSIS

Ahmed Fikry Attaallah, MD, PhD

BASICS DESCRIPTION

• Amyloidosis is a progressive connective tissue disease caused by the deposition of amyloid proteins. • It can involve various body systems but sometimes only one organ may be affected. Factors leading to the specific pattern of organ involvement are not understood. EPIDEMIOLOGY Incidence

New cases: 8 persons per million annually Prevalence

• 95% of cases are seen in people >40 years of age. • 66% of cases are men. • 15–20% of primary amyloidosis patients have associated multiple myeloma.

Morbidity

Varies between patients reflecting the extent of spread and the degree of organ dysfunction Mortality

• The average survival with primary amyloidosis is 12 months. • Amyloidosis associated with multiple myeloma is rapidly progressive and the life expectancy is usually <6 months. • In secondary amyloidosis, medical or surgical treatment of the underlying cause may slow or stop the disease progression. • In familial amyloidosis, survival is 7–15 years.

ETIOLOGY/RISK FACTORS

• Family history of amyloidosis • Advanced age • Chronic infectious or inflammatory diseases • Kidney disease requiring hemodialysis

PATHOPHYSIOLOGY

• The term “amyloid” describes an alteration in the secondary structure of a protein that results in an aggregated and insoluble form. Amyloidosis can result from inherited mutations in precursor genes or from plasma cell dyscrasia; amyloid deposits in the extracellular spaces lead to organ failure and eventually death.

• Plasma cells are located in the bone marrow and function as part of the immune system by producing antibodies. Monoclonal plasma cells produce small lambda (λ) or kappa (κ) fragments that are processed in an abnormal manner by macrophage enzymes producing the insoluble amyloid fibrils.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess for multiorgan involvement and the severity of disease progression in each system. • The anesthetic plan should focus on monitoring and preventing hemodynamic instability. • Maintain a high index of suspicion for a possible difficult intubation in order to prevent perioperative airway compromise. • Calcium channel blockers are contraindicated in cardiac amyloidosis and may produce or worsen bradyarrhythmias. Atropine may be useless or even worsen bradycardia in patients with familial amyloidosis. • Consider stress dose steroids for patients on chronic therapy.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Nervous system: Hand and foot numbness, visual changes, dementia • Cardiac: Decreased exercise tolerance, irregular heartbeat, syncope (strong predictor of sudden death) • Respiratory: Hoarseness of voice, shortness of breath, hemoptysis • Renal: Turbid urine, polyuria (early), or oliguria (late) • Digestive: Dysphagia, swollen tongue, dry mouth, constipation or diarrhea, hematemesis, melena, fresh bleeding, acid reflux

History

• Family history of amyloidosis • Onset of initial diagnosis • Coexisting chronic illness • Kidney failure/hemodialysis

Signs/Physical Exam

• Nervous system: Peripheral neuropathy, autonomic neuropathy (postural hypotension), visual field defects • Cardiac: Signs of restrictive cardiomyopathy and congestive heart failure, cardiomegaly, arrhythmias • Respiratory: Stridor, wheezing • Renal: Nephrotic syndrome, signs of renal failure • Digestive: Macroglossia, hemorrhage, hepatic enlargement and splenomegaly, signs of intestinal obstruction, malnutrition, and dehydration • Skin: Raised waxy papules or plaques

TREATMENT HISTORY

• Localized radiation therapy aimed at destroying the local collection of plasma cells

• Stem cell transplant • Surgical care: – Organ transplant surgery (liver, kidney, heart, or lung) – Carpal tunnel release – Percutaneous cementoplasty of bone lesions – Resection of bleeding friable amyloidomas in the respiratory, GI, or urinary tracts • Supportive care: – Renal: Hemodialysis and peritoneal dialysis – Cardiac: Pacemaker MEDICATIONS

• Melphalan and prednisone regimen is considered standard therapy. • An anthracycline analogue of doxorubicin, 4’-iodo-4’-deoxydoxorubicin, has been shown to solubilize amyloid fibrils. • Lenalidomide, a derivative of thalidomide, is an immunomodulator that has shown some success in patients. • In patients with coexisting multiple myeloma, vincristine, carmustine, dexamethasone, and cyclophosphamide can be used. • Proteasome inhibitor: Bortezomib may be used with relapsed/refractory myeloma.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Blood and urine tests are not diagnostic of amyloidosis, but can aid with monitoring organ dysfunction and disease progression: – Serum and urine protein analysis and immunoelectrophoresis – Impaired renal function tests – Impaired liver function tests • Hematologic indices and coagulation profile: Anemia, increased fibrinolysis, and clotting factors deficiency • Pathologic diagnosis: – Subcutaneous fat aspiration: Usually sufficient for diagnosis by immunostaining or fibril amino acid sequence analysis – Organ-specific biopsies: A needle biopsy of an involved organ ensures a cause-and-effect relationship between the organ dysfunction and amyloid deposition. – Bone marrow examination • Extent of disease spread: – Chest radiography – Bone imaging (skeletal survey) of the skull, pelvis, and entire spine – CT scan – MRI – Radioimmunodetection of amyloid deposits (SAP component scintigraphy or iodinelabeled pentagonal component scanning): A noninvasive method of quantitative imaging by iodine I123-labeled protein localizer that binds to amyloid deposits – Cardiac involvement: EKG can show a low-voltage QRS complex, conduction arrhythmias,

and bradycardia. Echocardiography can demonstrate concentric biventricular wall thickening, increased myocardial echodensity, restrictive filling pattern and diastolic dysfunction, thickened valves, and decreased myocardial contractility.

CONCOMITANT ORGAN DYSFUNCTION

• Varies depending on the nature of the chronic infectious or inflammatory diseases in secondary amyloidosis • Amyloid deposition can commonly affect the: – Cardiovascular system: myocardium, conduction system, and cardiac valves – Respiratory system: Upper and lower airways (the larynx is most common site) and the lungs (diffuse infiltration or tumorous masses) – Renal system: Kidneys, bladder – Digestive system: GI tract, liver, and spleen – Central and peripheral nervous systems

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Correction of electrolyte abnormalities • Correction of anemia and coagulopathy • Management of cardiac arrhythmias, including temporary or permanent pacemaker placement

CLASSIFICATIONS

• Primary amyloidosis (AL type): Most common, without pre-existing or coexisting disease • Secondary amyloidosis (AA type): Associated with a chronic infectious or inflammatory process • Amyloidosis with multiple myeloma (AL type) • Familial amyloidosis (AF type) • Local amyloidosis (AE type): Limited to a single organ • Senile (AS type): Aging—Alzheimer’s disease • Hemodialysis-related amyloidosis (AH type)

TREATMENT PREOPERATIVE PREPARATION Premedications

• Titrate sedation very cautiously; patients are prone to airway obstruction, particularly when macroglossia is present. • Appropriate pacemaker management

Special Concerns for Informed Consent

Advanced amyloidosis with severe organ dysfunction poses a high risk, and code status during the perioperative period should be clarified. INTRAOPERATIVE CARE

Choice of Anesthesia

• Consider regional or neuraxial blocks to avoid airway instrumentation in patients with tongue, larynx, and tracheal involvement that may lead to obstruction, hemorrhage, or difficult intubation. • On the other hand, in patients with peripheral neuropathy or coagulopathy, regional anesthesia is relatively contraindicated.

Monitors

• DC defibrillator and emergency medications should be readily available to treat cardiac arrhythmias and possible hemodynamic instability. • Invasive monitoring (arterial line, central venous access, and pulmonary artery catheter) and transesophageal echocardiography (TEE) should be determined on a case-by-case basis.

Induction/Airway Management

• Dose adjustment of induction drugs to avoid significant hypotension due to potential myocardial disease and reduced protein binding. • Patients may have undiagnosed supraglottic amyloid deposits (tongue, pharynx, and larynx), and blind placement of the endotracheal tube, nasal, or oral airways is not recommended since it may result in massive airway hemorrhage. • Perform a fiberoptic exam (before or after induction), or a careful direct laryngoscopy, to assess the feasibility of intubation. If extensive lesions are noted, an awake tracheostomy tube placement may be warranted. • If excision of the supraglottic lesions is planned, a small reinforced or laser cuffed endotracheal tube should be utilized. • Rapid-sequence induction is recommended if GI obstruction or delayed gastric emptying is present due to autonomic neuropathy. • In patients without aspiration or airway bleeding risks, a laryngeal mask airway (LMA) maybe used to avoid airway instrumentation.

Maintenance

• Impaired hepatic and renal functions may influence drug metabolism and clearance. • Ensure proper hydration but avoid intravenous overloading (limited cardiac and renal reserve). • Careful positioning to prevent nerve damage and fragile skin breakdown

Extubation/Emergence

• Patients who underwent upper airway or tracheobronchial lesion excisions need to be assessed for possible edema or bleeding and may be kept sedated and intubated postoperatively. • Avoid excessive coughing and straining to prevent skin eruptions and ecchymosis.

POSTOPERATIVE CARE BED ACUITY

• Patients with airway risk or with advanced amyloidosis who underwent major surgical

procedures may require an ICU bed and remain intubated with postoperative ventilation. • If an implantable defibrillator was programmed off, ensure that it is turned back on.

COMPLICATIONS

• Difficult, or impossible, ventilation due to subglottic amyloid deposits that may lead to tracheobronchial tree stenosis or hemorrhage. Treatment can be attempted with helium– oxygen mixture, jet ventilation, and emergency cardiopulmonary bypass through femoral access (guide-wires may be placed preoperatively). • Hypotension may be treated by inotropic agents and vasopressors. • Excessive bleeding can be treated by blood transfusion and correction of coagulopathies. • Bradycardia and conduction abnormalities can be treated by isoproterenol and cardiac pacing.

REFERENCES

1. Noguchi T, Minami K, Iwagaki T, et al. Anesthetic management of a patient with laryngeal amyloidosis. J Clin Anesth. 1999;11:339–341. 2. Minogue SC, Morrisson M, Ansermino M. Laryngo-tracheo-bronchial stenosis in a patient with primary pulmonary amyloidosis. Can J Anaesth. 2004;51(8):842–845. 3. Hirabayashi Y, Yokosuka S, Miyashita K, et al. Anesthetic management for a patient with amyloidosis. J Anesth. 1992;6(2):218–221.

ADDITIONAL READING

• Holmes RO, Baethge BA, Edison JD. Amyloidosis. July 2009. Available at: http://emedicine.medscape.com/article/335414-overview See Also (Topic, Algorithm, Electronic Media Element) • Difficult airway

CODES ICD9 • 277.30 Amyloidosis, unspecified • 277.39 Other amyloidosis ICD10 • E85.3 Secondary systemic amyloidosis • E85.9 Amyloidosis, unspecified

CLINICAL PEARLS

• Anesthesia providers must be aware of the multisystem involvement of amyloidosis and disease severity which varies between patients. The anesthetic plan must be tailored on a case-by-case basis with regard to complications that can arise.

• Life-threatening events include unanticipated loss of the airway and hemodynamic instability resistant to therapy.

AMYOTROPHIC LATERAL SCLEROSIS (ALS)/LOU GEHRIG’S DISEASE Christine E. Goepfert, MD, PhD, DESA

BASICS DESCRIPTION

• Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that involves select upper motor neurons (UMN) and lower motor neurons (LMN), often with involvement of the frontotemporal cortex, sensory cortex, and autonomic nervous system. • ALS manifests as a progressive loss of speech, swallowing, and motor function of the extremities as well as respiratory muscles. EPIDEMIOLOGY Incidence

• In the US: 1.89–2.16 per 100,000/year • Men > women 1.5:1 in sporadic ALS • Men = women in familial ALS • Rapid decrease after 80 years of age

Prevalence

• In the US: 2–5.2 per 100,000 • Peak age at onset: Overall 60 years. This value is usually lower in familial disease.

Morbidity

High risk of postoperative pulmonary complications (PPCs) secondary to the inability to clear secretions and carbon dioxide retention. The risk increases even further with a vital capacity that is 50% of predicted levels. Mortality

• Respiratory failure is the most common cause of death in over 84% of patients. • Average lifespan after diagnosis: 3–5 years. However, multidisciplinary care can increase survival. • Poorer prognosis is associated with bulbar palsy, advanced age.

ETIOLOGY/RISK FACTORS

Multifactorial with complex interaction between genetic and molecular pathways

• Genetic susceptibility: To date, 13 genes and loci have been identified (SOD1, TARDBP, FUS, ANG, OPTN). Familial ALS has a Mendelian pattern (5–10%). • Sporadic (SALS): Overlap with neurodegenerative disorders • Environmental factors: Extensive physical exertion (footballer), active service in US armed forces, cigarette smoking, neurotoxins (beta-methyl-amino-L-alanine), statins (under

discussion)

PATHOPHYSIOLOGY

The disease process involves glutamate-induced excitotoxicity, oxidative stress, mitochondrial dysfunction, impaired axonal transport, neurofilament aggregation, intra-cytoplasmic protein aggregates, inflammatory dysfunction, deficits in neurotrophic factors, and dysfunction of signaling pathways. ANESTHETIC GOALS/GUIDING PRINCIPLES

• There is an increased risk of PPCs, and perioperative efforts should aim at maintaining respiratory muscle strength and avoiding pulmonary aspiration. • Succinylcholine is absolutely contraindicated; the proliferation of extrajunctional receptors can result in life-threatening hyperkalemia.

PREOPERATIVE ASSESSMENT SYMPTOMS

Clinical hallmark is the presence of UMN and LMN features, involving brainstem and spinal cord regions: • Spinal onset in 75% (limbs, most common) • Bulbar onset in 25% • Initial trunk or respiratory involvement in 5% • Atypical onset: Weight loss, cramps without muscle weakness, cognitive dysfunction

History

Duration and progression: The median time to diagnosis is ∼14 months due to the insidious onset. Signs/Physical Exam

• Pulmonary: Observation of breathing, respiratory rate; auscultation; swallowing; coughing; salivation • Neurologic exam

TREATMENT HISTORY

• Supportive, palliative, and multidisciplinary management has been demonstrated to decrease the risk of death by 45% at 5 years. Symptomatic treatment is the cornerstone and involves: – Noninvasive ventilation: Prolongs survival and improves quality of life – Diaphragmatic pacing (DPS) – Invasive ventilation via tracheostomy (avoided in most patients) – Gastrostomy tube – Nutrition (50–60% of patients are hypermetabolic)

MEDICATIONS

• Riluzole (glutamate antagonist): Only drug shown to extend survival by ~2–3 months

– Most common side effects: Fatigue, nausea – ALT/SGPT levels rise in about 50% of patients. – Decreased lung function – Less common: Neutropenia, pain, dizziness, anorexia – Overdose: Encephalopathy with stupor/coma, methemoglobinemia • Common medications for symptomatic care: – Glycopyrronium, atropine, hyoscyamine – N-acetylcysteine – Benzodiazepines such as lorazepam – Dextromethorphan and quinidine – Baclofen and tizanidine – Anticonvulsants, e.g., carbamazepine – Opioids, e.g., morphine, in late state – Antidepressants, e.g., amitriptyline or SSRI – Modafinil

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC to assess for neutropenia from riluzole • Liver enzymes, especially ALT (affected by riluzole) • ABG to assess for hypercarbia • Pulmonary function tests – Spirometry: FVC – Maximum inspiratory pressure, sniff nasal inspiratory pressure of <40 cm H2O

• Polysomnography/nocturnal pulse oximetry: Desaturation, increased partial pressure of carbon dioxide • Electrophysiology: Nerve conduction, EMG, TMS, SEP • Muscle ultrasound • PET, MRI to exclude ALS mimics

CONCOMITANT ORGAN DYSFUNCTION

• Motor system: – Respiratory muscles: Caudal cranial nerve (bulbar) palsy: Dysphagia, loss of tongue mobility, impaired cough, swallow, gag reflex, dysarthria, or slurred/nasal speech Weakness of respiratory muscles: Dyspnea, orthopnea, desaturation, or cyanosis – Limbs: Muscle weakness (“lateral sclerosis”, refers to anterior and lateral corticospinal tracts replaced by gliosis) and atrophy (“amyotrophy") that starts distally and occurs more frequently in the upper extremities Fasciculations and cramps Hyperreflexia and spasticity • Sensory system, often subclinical: – Dysesthesia, pain and temperature, vibration and position

– Autonomic impairment (in 20%), often sympathetic hyperactivity • Neuropsychiatric symptoms: – Executive dysfunctions (frontal lobe) in 30–50%: Attention, disinhibition, decision making – Frontotemporal dementia in 5–15% with profound personality changes – Pseudobulbar affect: Emotional lability, pathologic laughter, and crying – Memory disturbance (temporal lobe)

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Critically reassess indication for surgery • Contemplate exclusion from surgery if the FVC is below 45% predicted; predicts the possibility of failure to extubate

CLASSIFICATIONS

• El Escorial Diagnostic Criteria: Physical examination, electromyography; neuroimaging to exclude other diseases • Awaji Criteria: More sensitive for early diagnosis • ALS Functional Rating Scale (ALSFRS): Activities of daily living

TREATMENT PREOPERATIVE PREPARATION Premedications

• Review concomitant medication and potential interactions with anesthetics • Caution with benzodiazepines is warranted (additive effect on respiratory depression). Alternatively, consider use of alpha 2-agonists such as clonidine, dexmedetomidine. • Consider starting NPPV if the FVC is <50% to accustom the patient prior to surgery.

Special Concerns for Informed Consent

• Executive function may be impaired in up to 50% of patients; consent may be necessary from a power of attorney/family member. • Discuss potential postoperative respiratory failure: ICU stay, weaning failure, and/or tracheostomy. There is a considerable increase in respiratory complications with repeated general anesthesia/surgery. • Patient autonomy and the right of the patient to refuse or withdraw any treatment, including mechanical ventilation, should be respected. INTRAOPERATIVE CARE Choice of Anesthesia

• Regional techniques, including epidural anesthesia, may be considered in individual cases after careful assessment of risks and benefits (“double-crush” phenomenon vs. respiratory problems). • General anesthesia – May exacerbate respiratory insufficiency significantly – Choose short-acting drugs, if possible

Monitors

• Standard ASA monitors • Advanced monitoring should be guided by concomitant diseases and surgery.

Induction/Airway Management

• Opioids and sedatives of choice; avoid excessive sedation • Succinylcholine is absolutely contraindicated due to denervated muscles and the proliferation of extrajunctional receptors. Can cause hyperkalemia. • Risk of arterial hypotension due to suppression of sympathetic stimulation; have vasopressors available.

Maintenance

• Any hypnotic agent may be utilized. • Opioids: Any opioid may be administered; however, remifentanil is specifically advantageous: – Metabolism is independent of liver function (riluzole). – Very short half-life – High dosages can provide deep levels of anesthesia that preclude the need for muscle relaxants. • Muscle relaxants: – Caution with all non-depolarizing muscle relaxants since they may cause prolonged and pronounced neuromuscular blockade; consider low-dose cisatracurium. – Contemplate alternatives, if feasible, such as use of topical lidocaine, deep intubation, or use of an LMA – If used, neuromuscular monitoring is mandatory. – Anticholinesterases should be used and properly dosed to ensure adequate reversal. • Adequate hydration

Extubation/Emergence

• Patient may not meet extubation criteria. • Laryngospasm

POSTOPERATIVE CARE BED ACUITY

• Routinely monitored overnight due to the risk of apnea; the outpatient setting is not recommended even for minor procedures. • ICU bed if necessary; patient may require prolonged postoperative ventilation.

MEDICATIONS/LAB STUDIES/CONSULTS

• Respirometer, vital capacity • ABG to assess for hypercarbia (may present as confusion or sedation) • The routine use of oxygen is not recommended due to the instability of the respiratory drive. • Continue NPPV if the patient was on NPPV before • Communication is often difficult (dysarthria, dementia): Organize a primary caregiver who

is often better able to communicate. • Pulmonology consult recommended

COMPLICATIONS

• Arterial hypotension • No risk for malignant hyperthermia with common triggering agents • Respiratory complications: – Hypercarbia – Increased risk for pneumonia due to aspiration and immobility

REFERENCES

1. Onders RP, Carlin AM, Elmo M, et al. Amyotrophic lateral sclerosis: The Midwestern surgical experience with the diaphragm pacing stimulation system shows that general anesthesia can be safely performed. Am J Surg. 2009;197(3):386–390. 2. Paek CM, Yi JW, Lee BJ, et al. No supplemental muscle relaxants are required during propofol and remifentanil total intravenous anesthesia for laparoscopic pelvic surgery. J Laparoendosc Adv Surg Tech A. 2009;19(1):33–37. 3. Bedlack RS. Amyotrohic lateral sclerosis: Current practice and future treatment. Curr Opin Neurol. 2010;23:524–529. 4. Cavallucci V, D’Amelio M. Matter of life and death: The pharmacological approaches targeting apoptosis in brain diseases. Curr Pharm Des. 2011;17(3):215–229. 5. Kieman MC, Vucic S, Cheah BC, et al. Amyotrophic lateral sclerosis. Lancet. 2011;377:942– 955. 6. Wijesekera LC, Leigh PN. Amyotrophic lateral sclerosis. Orphanet J Rare Dis. 2009;4:3. See Also (Topic, Algorithm, Electronic Media Element) • Postoperative pulmonary complications • Tracheostomy

CODES ICD9 335.20 Amyotrophic lateral sclerosis ICD10 G12.21 Amyotrophic lateral sclerosis

CLINICAL PEARLS

• Despite significant recent advances in knowledge about ALS, treatment is still focused on improvement of quality of life. • Respiratory failure is by far the most common cause for death in ALS patients and is exacerbated by surgery and anesthesia.

• General anesthesia is usually preferred. • Succinylcholine is absolutely contraindicated, and nondepolarizing neuromuscular blockade needs to be monitored very closely.

ANAEROBIC METABOLISM Amar M. Bhatt, MD Ravi S. Tripathi, MD

BASICS DESCRIPTION

• Anaerobic metabolism is the body’s mechanism of continually responding to stress and sustaining life-preserving measures during malperfusion, until favorable conditions are resumed. • The human body’s major source of energy comes from the consumption of glucose via aerobic methods: – Aerobic metabolism: Occurs when there is an adequate delivery of oxygen. The O2

molecule functions as an electron acceptor to produce a maximal amount of energy in the form of ATP (adenosine triphosphate). – Anaerobic metabolism: Occurs during times of malperfusion and oxygen supply–demand mismatch. The body generates ATP via a rapid, oxygen-free variation of glycolysis with lactate as a byproduct (the Pasteur Effect).

PHYSIOLOGY PRINCIPLES

• ATP is a nucleotide that provides chemical energy for all cells in the body; it is produced via carbohydrate (primarily) and non-carbohydrate metabolism. • Aerobic metabolism (oxygen-dependent) occurs via metabolism of glucose within the cytoplasm and mitochondria; each molecule of glucose is capable of producing 36 ATP. – Glycolysis: Glucose is a 6-carbon structure that is first broken down into pyruvate, a 3carbon structure. This process takes place in the cytoplasm and results in the net production of 2 ATP. – Citric acid cycle (Krebs’ cycle): Using the pyruvate molecules and available oxygen, the citric acid cycle generates 2 additional ATP per original glucose molecule via an 8-step process and 18 different enzymes. In addition, this also generates NADH, FADH2, and other byproducts (e.g., GTP) that can be converted to ATP. – Oxidative phosphorylation: NADH and FADH2 are metabolized in the mitochondria to

create an additional 24 molecules of ATP per original glucose molecule. This occurs via oxidative phosphorylation (the electron transport chain), driven by a proton gradient. • Gluconeogenesis: In the absence of readily available supplies of glucose, the body is able to use non-carbohydrates (e.g., lactate, glycerol, and certain amino acids or fatty acids) to generate glucose. Gluconeogenesis takes places via enzymes found in the cytoplasm and mitochondria of hepatic cells; liver dysfunction or failure can, thus, result in hypoglycemia and require supplemental dextrose solutions. • Glycogenolysis: The body can also convert complex carbohydrates, such as glycogen, to glucose. This pathway occurs in the liver and muscle; it also requires a functioning liver.

• Anaerobic metabolism (oxygen-independent) occurs when the demand for oxygen is greater than its supply. For each glucose molecule, only 2 ATP are produced. – In states where oxygen is reduced/absent, pyruvate is metabolized to lactate via lactate dehydrogenase as an end-product of anaerobic metabolism (pyruvate lactate dehydrogenase) – Physiologic states (exercise): The anaerobic threshold is a theoretical point during dynamic exercise when muscle tissue switches over to anaerobic metabolism as an additional energy source. – Pathologic states: Stress, hypoxia, or hypotension/shock • Central nervous system: The CNS consumes large amounts of energy to maintain normal electrical function and cellular metabolism. – Because it cannot store ATP, it requires a constant supply of both glucose and oxygen (∼3–3.5 mLO2/100 g/min).

– Anaerobic metabolism can result in a 95% decrease in energy production per available glucose. This can further worsen ischemic damage. – It is not capable of utilizing amino acids or fatty acids as alternative sources of energy. Thus, hypoxia, hypoglycemia, or impaired perfusion can rapidly lead to inadequate energy levels. • Myocardium: Due to its demand for a constant source of energy, cardiac muscle is highly dependent on the aerobic metabolism of fats, carbohydrates, and amino acids. Under ischemic or hypoxic conditions, the energy liberated by lactate production or anaerobic metabolism (as compared to aerobic metabolism) is not sufficient for myocardial function and ventricular contraction. • Pulmonary: Lactic acidosis stimulates peripheral and central chemoreceptors to augment the medullary respiratory center. This leads to a compensatory increase in oxygen intake and excretion of carbon dioxide. As with any change in acid–base homeostasis, the ventilatory response to acidosis is driven primarily by central chemoreceptors; whereas peripheral chemoreceptors are primarily affected by hypoxemia. • Hemoglobin: Acidosis decreases the affinity of hemoglobin for oxygen; it improves oxygen uploading/delivery to acidotic tissue. This is expressed as a right shift in the oxygen– hemoglobin dissociation curve.

ANATOMY

Erythrocytes do not possess mitochondria. DISEASE/PATHOPHYSIOLOGY

• Lactate accumulation occurs during anaerobic metabolism and results in an anion gap metabolic acidosis. – An anion gap is a term used to describe "unmeasured anions” (e.g., lactate, ethanol, uremia, certain toxins, ketones) during states of metabolic acidosis. – Normal lactate concentrations range from 0.5 to 1.0 mmol/L in healthy individuals and up to 2.0 mmol/L in the critically ill. – Base excess is more commonly measured in the perioperative period. • Perioperative lactic acidosis indicates tissue hypoxia from any combination of the following: – Hypovolemia (e.g., hemorrhagic shock in a trauma patient)

– Hypoperfusion (e.g., cardiogenic shock following cardiac surgery or myocardial ischemic events) – Hypotension (e.g., vasodilatory shock in a septic patient) – Multifactorial from a combination of the above. For example, a trauma patient suffering myocardial contusions and a perforated viscus could have a combination of hypovolemia, hypoperfusion, and hypotension. • Lactic acidosis leads to several cellular and microvascular changes in tissues (1). – May aggravate structural damage of neurons and glia in the cerebral cortex – In an attempt to maintain a normal acid–base environment, cells utilize protein transporters and enzymes via an active process to maintain a homeostatic concentration of carbon dioxide, bicarbonate, and protons.

PERIOPERATIVE RELEVANCE

• Hyperlactatemia can result from: – Increased lactate production (Type A): Due to anaerobic metabolism – Decreased lactate clearance (Type B): Due to liver disease, hypermetabolic states, and inhibition of pyruvate dehydrogenase – Some patients may develop lactic acidosis from both mechanisms (e.g., liver failure and shock). – Measuring pyruvate can assist in the differentiation of Type A and Type B lactic acidosis. A lactate-to-pyruvate ratio >25:1 supports the underlying mechanism of tissue hypoxia or Type A lactic acidosis. A normal lactate-to-pyruvate ratio (10:1) supports Type B lactic acidosis. • Anaerobic metabolism is not an uncommon physiologic derangement seen in the perioperative arena; it can result when there is a mismatch of oxygen delivery and demand: – Hypoxia/hypoxemia: Esophageal or mainstem intubation, hypoxic mixture, hypoventilation, V/Q mismatch, shunt – Hypoperfusion: Hypotension, hypovolemia, hemorrhage, myocardial impairment, shock – Vasodilation: Anesthetic medications, neuraxial blocks; anaphylactic or septic shock • Cardiopulmonary bypass: Lactate is associated with malperfusion (2). It not only allows for prognostication, but also serves as an indicator of the efficacy of therapies used to restore tissue perfusion. – Hyperlactatemia is associated with longer intensive care stays and increased postoperative ventilatory support, renal dysfunction, infectious complications, and circulatory disorders. – Titrating therapies to traditional endpoints may not ensure that the microvascular bed is perfused. For example, a normal or high blood pressure may be a vasoconstrictive response to a low cardiac output state. • Septic shock: Hyperlactatemia is typically present in patients with sepsis or septic shock and the etiology is multifactorial (3). – Hypovolemia: Septic shock is associated with fluid-responsive physiology. Thus, an elevated lactate level could indicate a “dry” patient. – Hypoperfusion: Sepsis is also accompanied by a hypermetabolic state with enhanced glycolysis. Patients with “normal” filling pressures (e.g., central venous pressure) and cardiac indices (e.g., cardiac index) may not have adequate oxygen delivery. – Cytopathic hypoxia: Despite adequate volume status and perfusion, tissue dysfunction at

the cellular level may persist in sepsis and represents impaired cellular function. – Lactate is a well-established prognostic indicator in sepsis and septic shock. Obtaining serial serum lactate levels aids in identifying tissue hypoperfusion in patients who are not hypotensive but are at risk for septic shock; an elevated lactate (>4 mmol/L or 36 mg/dL) likely indicates inadequate oxygen delivery. Early goal-directed therapy should be considered in patients with sepsis and/or an elevated lactate level. – As part of the Surviving Sepsis Guidelines, a resuscitation bundle for patients with sepsis includes, but it is not limited to: A minimal initial crystalloid bolus of 20 mL/kg or equivalent Vasopressor therapy to maintain a mean arterial pressure >65 mm Hg Obtaining blood cultures and administering appropriate antibiotic therapy Maintaining adequate central venous pressure and central venous oxygen saturation

EQUATIONS

• Glucose + 2 ADP + 2 Pi → 2 Lactate + 2 ATP + 2 H2O • Pyruvate + NADH + H+ ←→Lactate + NAD+

REFERENCES

1. Cassavaugh J, Lounsbury KM. Hypoxia mediated biological control. J Cellular Biochem. 2010;112(3):735–744. 2. Javidi L. Pathophysiology of lactic acidosis and its clinical importance after cardiac surgery. Iran J Cardiac Surg. 2008;2:18–24. 3. Dellinger RP, Levy MM, Carlet JM, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock. Crit Care Med. 2008;36:1394–1396.

ADDITIONAL READING

• Chaitman BR. Exercise stress testing. In: Bonow RO, Mann DL, Zipes DP, et al, eds. Braunwald’s heart disease—a textbook of cardiovascular medicine, 9th ed. Philadelphia, PA: Saunders/Elsevier, 2011, chap. 14. • Levy B. Lactate and shock state: The metabolic view. Curr Opin Crit Care. 2006;12(4):315– 321. • Surviving Sepsis Campaign. www.survivingsepsis.org See Also (Topic, Algorithm, Electronic Media Element) • Base excess • Metabolic acidosis • Septic shock • Cardiopulmonary bypass (CPB)

CLINICAL PEARLS

• Lactate production can serve as a marker of anaerobic metabolism and tissue hypoxia. • When there is concern for adequate oxygen delivery, lactate and base deficit measurements can serve as markers of adequate tissue perfusion.

ANAPHYLAXIS Lori Gilbert, MD

BASICS DESCRIPTION

• An acute, life-threatening reaction with an onset of minutes to hours. It is usually, but not always, the result of an immunologic mechanism that involves IgE-mast cell or basophil mediator release; such mediators can include histamine, leukotrienes, and prostaglandins. • The newest definition of anaphylaxis encompasses 1 of 3 scenarios: – Acute onset (minutes to hours) of skin and mucosal manifestations, as well as respiratory compromise, hypotension, or shock – Signs as above, after exposure to a likely antigen, in addition to GI symptoms – Hypotension after exposure to a known antigen EPIDEMIOLOGY Prevalence

• During anesthesia: Ranges from 1:4,000 to 1:25,000 anesthetics • Hospital inpatients in the US: 1:3,000; in Europe, the incidence is reported to be much lower. • In the US, it is estimated that between 1.25% and 16% of the general population is at risk for possibly experiencing an episode of anaphylaxis. Prevalence

• Lifetime prevalence from all triggers: 0.05–2% • Food triggers: 90% of anaphylaxis cases are caused by milk, soy, eggs, wheat, peanuts, tree nuts, fish, and shellfish. Morbidity

• Food allergies account for 30,000 ER visits a year; it is more common among children than adults. • Latex anaphylaxis is responsible for >200 cases/year.

Mortality

• In the US: ∼2 in 100,000 anaphylaxis cases • In the UK: 0.65–2% of anaphylaxis cases • Risk factors age 10–35 years old: Active asthma, peanut allergy, and delayed administration of epinephrine • Risk factors age 55–85 years old: Cardiovascular or respiratory illness, use of antibiotics or anesthetic agents. ETIOLOGY/RISK FACTORS

• History of a prior anaphylactic episode remains the most important factor in establishing cause and risk factors. • Outpatient setting: – Drug-induced: Penicillin and other antibiotics, aspirin, and NSAIDs – IV contrast dye – Food: Peanuts, tree nuts, fish, shellfish, soy, egg, cow’s milk – Other: Exercise-induced, idiopathic, insect stings, seminal fluid • Perioperative setting: – Neuromuscular blockers (most common) – Natural rubber latex – Antibiotics – Hypnotics (propofol, thiopental) – Aprotinin – Bupivacaine – Radiographic contrast material – Opioids – Protamine – Blood transfusions – Methylmethacrylate (bone cement; associated with hypotension but no IgE mechanism has been found) – Rare causes include etomidate, ketamine, midazolam, and amide local anesthetics.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Anaphylactic and anaphylactoid reactions stem from the systemic release of mediators from mast cells and basophils. The pathogenesis of anaphylactic reactions involves an immunologic mechanism in which IgE is created in response to allergen exposure. Receptors on the surface of mast cells and basophils bind with IgE. • Re-exposure of the allergen results in activation of IgE-bound mast cells and basophils with the resultant release of pre-formed mediators that are stored in cellular granules (histamine, tryptase, heparin, chymase, cytokines). In addition, arachidonic acid is metabolized to prostaglandins and leukotrienes and also released. • Anaphylaxis often produces signs and symptoms within minutes of exposure but there are also biphasic reactions that can occur 1–72 hours after the initial attack. • Increased vascular permeability is a hallmark of anaphylaxis that allows the transfer of large amounts of intravascular fluid into the extravascular space within 10 minutes. As a result, cardiovascular collapse may be the first sign of anaphylaxis with little or no cutaneous or respiratory signs.

PREVENTATIVE MEASURES

• Primary prevention is based on allergen desensitization through immunotherapy. • Venom immunotherapy is highly successful in preventing anaphylaxis. • Pharmacologic prophylaxis (steroids, antihistamines) can be used to help prevent occurrences to radiographic contrast material, fluorescein, and other dyes. • For idiopathic anaphylaxis, prophylaxis with daily oral prednisone, combined with H1 antagonists, has resulted in decreased incidence.

• Most importantly, patient education and avoidance of known triggering substances is key in prevention. • A “TIME OUT" should be performed prior to any procedure and identify the presence of any known drug allergies.

PREOPERATIVE ASSESSMENT • Acute onset of reaction (minutes to hours) • Cutaneous: Skin, mucosa, or both can present with hives, urticaria, angioedema, pruritus, flushing, swollen lips and tongue. • Respiratory: Bronchospasm, wheezing, dyspnea, stridor, reduced peak expiratory flow, hypoxemia, respiratory arrest • Cardiovascular: Hypotension or symptoms of end-organ dysfunction (cardiovascular collapse), tachycardia • Gastrointestinal: Persistent vomiting, diarrhea • RAST testing (radioallergosorbent test) detects specific IgE antibodies to suspected or known allergens. The suspected antigen is bound to an insoluble material and the patient’s serum is added. If the serum contains antibodies to the allergen, those antibodies bind to the allergen. Radiolabeled anti-human IgE antibody is added where it binds to those IgE antibodies already bound to the insoluble material. • Skin manifestations may be masked by surgical drapes and are not as common in the setting of general anesthesia as in other settings. • Bradycardia is, surprisingly, more common with anaphylaxis in the setting of general anesthesia (not tachycardia). • Cardiovascular collapse may be the only sign of anaphylaxis.

DIFFERENTIAL DIAGNOSIS

• Acute asthma exacerbation • Syncope • Panic attack/anxiety disorders • Acute generalized hives • Vocal cord/paradoxical vocal cord dysfunction • Vasovagal reactions • Nonimmunologic reactions that involve mechanisms outside of IgE mediation (transfusion reactions, IgG or IgM antibody-mediated, antigen–antibody complexes and complement) • Anaphylactoid reactions: The World Allergy Organization has suggested that the term be eliminated in favor of calling all similar reactions “anaphylaxis.” Generally, the term is used to describe non-IgE-mediated reactions; the initial treatment is the same, regardless of the mechanism. • Cardiovascular disorders: Pulmonary embolism, cardiogenic shock, etc. • Flushing disorders: Carcinoid, “red-man” syndrome from vancomycin, medullary carcinoma of the thyroid • Other: Mastocytosis (systemic mast cell disease [SCMD]) is a clonal disorder characterized by overproduction of mast cells in different tissues. • Postprandial syndromes

• Diagnostic tests and interpretation: – Serum tryptase peaks 60–90 minutes after the onset of anaphylaxis and persists for 6 hours; obtain between 1 and 2 hours after the first symptoms appear. – Plasma histamine levels begin to rise within 5–10 minutes and remain elevated for 30–60 minutes. – 24-hour urinary histamine metabolite – Urinary vanillylmandelic acid to rule out pheochromocytoma and carcinoid syndrome – Skin tests (or in vitro tests) determine the presence of specific IgE antibodies to foods, medications (e.g., penicillin).

TREATMENT • Discontinuation of the inciting factor (e.g., anesthetic agent or drug) • Place the patient in the recumbent position (pertinent if antibiotics or medication is being given on the floor or preoperative holding area) • ABC’s: Manage airway, delivery 100% oxygen, and intubate (if appropriate) • Rapid IV fluid replacement • Epinephrine is the most important aspect of treatment for anaphylaxis and should be administered immediately: – IV: 5–10 mcg boluses – IV drip: 1 mcg/min – SQ: 200–500 mcg q5 minutes (aqueous 1:1,000 dilution which is equivalent to 1 mg/mL or 0.2–0.5 mL) – IM: 200–500 mcg into the vastus lateralis, or lateral aspect of the thigh (aqueous 1:1,000 dilution which is equivalent to 1 mg/mL or 0.2–0.5 mL) – Cardiopulmonary arrest during anaphylaxis: 1–3 mg IV over 3 minutes, followed by 4–10 mcg/min infusion – Severe or refractory anaphylaxis that is unresponsive to epinephrine has been reported with patients on beta-blockers; it has been characterized by bradycardia, profound hypotension, and severe bronchospasm; consider treating with glucagon 1–5 mg IV over 4 minutes, followed by an infusion of 5–15 mcg/min. • Histamine 1 blocker. Diphenhydramine 1–2 mg/kg or 25–50 mg IV dose. • Histamine 2 blockers. Ranitidine 50 mg IV diluted in 5% dextrose (total volume of 20 mL) can be administered over 5 minutes. Alternatively, cimetidine 4 mg/kg IV may be given. • Inhaled beta-2 agonists if bronchospasm is present • Glucocorticoids are not helpful acutely but potentially can help prevent recurrences and shorten the duration of attack. • Monitors: Large-bore IV access, if not already in place, should be placed. Arterial line placement can aid with monitoring blood pressure (particularly if chest compressions); however, it should not interfere with immediate resuscitation with IV fluids and epinephrine.

FOLLOW-UP

• Biphasic anaphylaxis can occur in up to one-fourth of episodes, and symptoms may recur within hours after apparent resolution of initial presentation. • Following resolution of the initial episode, patients should be provided with an epinephrine pen and instructions for administration as well as instructions to go to the nearest emergency room at the first hint of recurrence of symptoms. • Patients should also be referred to an allergist/immunologist for further workup, possibly including skin testing and desensitization, if appropriate.

REFERENCES

1. ieberman P, Nicklas R, Oppenheimer J, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010;126:477–480.

2. Hepner D, Castells M. Anaphylaxis during the perioperative period. Anesth Analg. 2003;97:1381–1395. 3. Estelle F, Simons R. Anaphylaxis. J Clin Immunol. 2010;S161–S180. 4. Kemp S, Lockey R. Anaphylaxis: A review of causes and mechanisms. J Allergy Clin Immunol. 2002;110(3):341–348. 5. Leiberman P. Anaphylactic reactions during surgical and medical procedures. J Allergy Clin Immunol. 2002;110(2):s64–s69. 6. Matasar M, Neugut A. Epidemiology of anaphylaxis in the United States. Curr Allergy Asthma Rep. 2003;3:30–35.

ADDITIONAL READING • www.aaaai.org • www.acaai.org • www.aafa.org

See Also (Topic, Algorithm, Electronic Media Element) • Latex allergy

CODES ICD9 • 995.0 Other anaphylactic reaction • 995.60 Anaphylactic reaction due to unspecified food ICD10 • T78.00XA Anaphylactic reaction due to unspecified food, init encntr • T78.2XXA Anaphylactic shock, unspecified, initial encounter • T78.2XXD Anaphylactic shock, unspecified, subsequent encounter

CLINICAL PEARLS

• Epinephrine, patient position, and oxygen are the most important therapeutic modalities in treating anaphylaxis. Treatment (in order of importance) includes: – Epinephrine – Patient position (recumbent) – Oxygen – IV fluids – Nebulized beta-2 agonists – Vasopressors – Antihistamines – Corticosteroids • Propofol and egg allergy: This topic has been a source of some controversy among anesthesia providers. Propofol is formulated in a lipid emulsion containing soybean oil, glycerol, egg lecithin, and disodium edetate with sodium hydroxide to adjust for pH. – The egg lecithin component is a highly purified egg yolk component. The principal protein of eggs is ovalbumin which is present in the egg white. Most egg allergies are related to the egg white (albumin) and not the egg yolk (lecithin). – Most allergic-type reactions to propofol are nonimmunologic because propofol can cause direct stimulation of histamine release. – Skin testing of egg-allergic patients is not consistent with allergies to propofol. – However, there are case reports in the literature of anaphylaxis associated with propofol in egg-allergic individuals. – Furthermore, the propofol package insert monograph clearly states under contraindications: “Propofol Injectable Emulsion is contraindicated in patients with allergies to eggs, egg products, soybeans or soy products.” • It is the author’s opinion that if propofol can be avoided in egg-allergic individuals, then an appropriate substitute should be used. If propofol cannot be avoided, epinephrine, largebore IV access, and resuscitation equipment should be readily available.

ANEMIA

Gregory M. T. Hare, MD, PhD Katerina Pavenski, MD, FRCPC

BASICS DESCRIPTION

• Anemia is defined as a hemoglobin concentration <12 g/dL in females and <13 g/dL in males. • Red blood cells (RBCs) with normal functioning hemoglobin (Hg) are essential for delivering oxygen to tissues. They also contribute to blood viscosity and may aid in hemostasis. EPIDEMIOLOGY Prevalence

• Highly variable and dependent on the etiology and patient demographics (1) • 11–76% of patients may present with preoperative anemia. Postoperative anemia may be present in up to 90% of patients undergoing major surgery (2,3).

Prevalence

An estimated 25% of the world’s population is anemic from nutritional, infectious, malignancy, and genetic causes. Iron deficiency is the most common type of anemia worldwide, and accounts for ∼50% of all cases (4). Morbidity

Acute and chronic anemia is associated with an increased risk of stroke, myocardial infarction, and renal injury in specific patient populations (2,5). Anemia is associated with increased perioperative morbidity and higher likelihood of requiring an allogeneic transfusion which is in turn associated with prolonged hospital stay and postoperative infections (6), and increased risk of mortality (2). Mortality

Preoperative anemia is an independent risk factor for mortality and is associated with a greater likelihood of requiring allogeneic blood transfusion which has also been linked to increased mortality in surgical and critical care patients (2).

ETIOLOGY/RISK FACTORS

• Decreased or impaired production – Nutritional deficiencies (iron, folate, vitamin B12) – Reduced erythropoietin (EPO) production due to renal failure – Bone marrow causes: Aplastic anemia, dysplasia/cancer, or fibrosis – Chronic inflammation (also known as anemia of chronic disease [ACD]) • Increased destruction (hemolysis)

– Intrinsic to RBCs Membrane disorders Hemoglobinopathies: Sickle cell disease, thalassemia Enzyme deficiencies – Extrinsic to RBCs Immune (allo or autoantibody mediated) Microangiopathy (disseminated intravascular coagulation, thrombotic thrombocytopenic purpura) Macroangiopathy (leaky valve) – Infections (malaria) Other (burns) • RBC loss – Bleeding (GI bleeding, menorrhagia, surgery, etc.) – Blood donation • RBC sequestration (related to splenomegaly) • Dilution – Iatrogenic (e.g., resuscitation with crystalloid) – Pregnancy

PHYSIOLOGY/PATHOPHYSIOLOGY

• The mechanisms of anemia-induced morbidity and mortality have not been clearly established. However, inadequate blood oxygen content and tissue oxygen delivery likely contribute (2,7). • Iron deficiency can result from poor nutritional intake, increased requirements (childhood, pregnancy, breastfeeding), chronic blood loss, and impaired absorption (1). • Vitamin deficiency can result from poor oral intake, impaired absorption or increased requirements (e.g., folate deficiency in hemolysis). • Renal failure leads to impaired EPO production which in turn results in anemia. • ACD is a result of chronic inflammation. Pro-inflammatory mediators and RES cells induce changes in iron homeostasis, proliferation of erythroid progenitor cells, production of EPO, as well as affect the life span of red cells leading to anemia. • Hemolytic anemia is a result of impaired red cell survival due to a variety of factors, and can be either hereditary or acquired. • Malignancy, both hematological and solid, may lead to anemia due to tumor occupying the bone marrow, or bone marrow suppression resulting from the treatment of malignancy (irradiation, chemotherapy) or from ACD. • In addition to iron deficiency, pregnancy leads to increased plasma volume and dilutional anemia. Dilutional anemia may also result from aggressive crystalloid resuscitation of patients who present with bleeding.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Each unit of transfused RBCs increases the Hg level by ∼1 g/dL and Hct by 3%. • The decision to transfuse should not be based solely on Hg level; the clinical situation must be taken into account. Most guidelines recommend transfusion for a euvolemic Hg <6.5 g/dL. Transfusion is almost never indicated for a euvolemic Hg level >10 g/dL. The area

between 6.5 and 10 dg/L is a gray zone, and the decision to transfuse should depend upon clinical circumstances including ongoing blood loss, presence of relevant comorbidities, symptoms of anemia, and signs indicative of inadequate oxygen delivery or hemodynamic instability.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Fatigue, lightheadedness, syncope, impaired mentation • Palpitations • Shortness of breath and/or chest pain on exertion • Jaundice, dark urine, gallstones (suggestive of hemolytic anemia)

History

• History of anemia, investigations, and treatments to date • History of chronic inflammatory conditions (lupus, arthritis) • History of major organ dysfunction: Kidney, heart, liver, lungs • Illicit drugs and alcohol intake • History of cancer and its treatment • History of chronic blood loss • History of GI disorders and surgery • Known diagnosis of hereditary RBC disorder

Signs/Physical Exam

• Pale conjunctivae • Tachypnea, tachycardia, systolic murmur, signs of CHF • Masses, lymphadenopathy, organomegaly

TREATMENT HISTORY

Iron, erythropoiesis-stimulating agents (ESA), Vitamin B12, folate, transfusions MEDICATIONS

Medications with myelotoxic potential: Immunosuppressive agents (e.g., Imuran), chemotherapy (e.g., cyclophosphamide), anticonvulsants, etc. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hg, RDW, MCV (mean corpuscular volume). A low MCV (microcytic anemia) may indicate iron deficiency anemia (IDA) or thalassemia. A high MCV may be suggestive of vitamin B12 or folate deficiency, liver disease, and excessive alcohol intake. • Reticulocyte count reflects the adequacy of bone marrow compensation for anemia. A low reticulocyte count in the face of significant anemia suggests either a lack of hematinics or a bone marrow problem. • Blood film

• Ferritin, serum iron, TIBC, iron saturation. A low ferritin and iron saturation point to iron deficiency anemia (IDA). Note: Ferritin is an acute phase reactant, and may not be an accurate marker of iron stores in a patient with chronic inflammation. • Soluble transferrin receptor may help differentiate between IDA and ACD. A low-soluble transferrin receptor is indicative of ACD. • Folate, vitamin B12 • CRP is a marker of inflammation, and may be helpful in assessing patients with suspected ACD. • Standard biochemistry tests, such as creatinine, transaminases, and bilirubin, are useful to determine the presence or extent of either renal or liver disease.

CONCOMITANT ORGAN DYSFUNCTION

Concomitant lung or heart disease may lower the body’s ability to compensate for anemia. These patients may have symptoms of anemia at higher Hg levels than their healthy peers. CIRCUMSTANCES TO DELAY/ CONDITIONS

• Symptoms of impaired oxygen delivery to the cerebral or myocardial system • If significant anemia (Hg <10 g/L) is present and surgery could be safely postponed, a patient should undergo evaluation by an internist or hematologist and treated for anemia prior to surgery. This is especially true for patients who will be undergoing high blood loss procedures, have a rare blood type, or significant alloimmunization against RBC antigens, or those who object to blood transfusion for religious reasons.

CLASSIFICATIONS

• Morphological: Microcytic, macrocytic, normocytic • Kinetic: Decreased RBC production, increased RBC destruction, increased RBC loss, sequestration and dilution

TREATMENT PREOPERATIVE PREPARATION Premedications

• Attempt to correct anemia with hematinics (vitamins or minerals) and ESA as necessary (8) • If there is significant anemia and surgery is urgent (e.g., there is no time to institute blood conservation measures or see their benefit), an allogeneic RBC transfusion may be necessary. • Consider administration of antifibrinolytic agents (e.g., tranexamic acid) and topical hemostatic agents to reduce blood loss Special Concerns for Informed Consent

• Discuss the possibility of blood product transfusion and describe associated risks • Describe risks and benefits of the proposed blood conservation measures (e.g., thromboembolic risk with ESA) INTRAOPERATIVE CARE

Choice of Anesthesia

Depends on the surgical procedure. The sympatholysis from neuraxial techniques may be profound. Monitors

Standard ASA monitors

Induction/Airway Management Prepare for hypotension Maintenance

• Blood loss intraoperatively is whole blood loss. Laboratory values may not reflect this initially until volume replacement has occurred. • Assess blood loss on laps, sponges, drapes, floor, as well as the suction canister • Consider cell salvage • Avoid hypothermia • Use point of care testing (if available and appropriate) to guide hemotherapy

Extubation/Emergence

Postoperative intubation and ventilator support may be considered when large volume shifts and transfusion have taken place.

FOLLOW-UP BED ACUITY

Not applicable

MEDICATIONS/LAB STUDIES/CONSULTS

• Follow Hg levels closely, as well as symptoms and bleeding; consider transfusion as appropriate. Over-transfusion should be avoided; in stable patients, transfuse 1 unit at a time followed by reassessment. • Eliminate unnecessary blood draws; collect samples into pediatric tubes. • Consider consulting hematology or the blood conservation service to assist with iron supplementation and other medical therapy for optimization of Hg. • Do not forget about appropriate thromboprophylaxis especially for those patients who have received ESA and tranexamic acid (TXA) perioperatively.

REFERENCES

1. de Benoist B, McLean E, Egli I, et al., eds. Worldwide prevalence of anaemia 1993–2005. 2. Geneva, Switzerland: World Health Organization, 2008. 3. Shander A, Javidroozi M, Ozawa S, et al. What is really dangerous—anemia or transfusion. Br J Anaesth. 2011;107(Suppl 1):i41–i59. 4. Beris P, Munoz M, Garcia-Erce JA, et al. Perioperative anaemia management: Consensus

statement on the role of intravenous Iron. Br J Anaesth. 2008;100:599–604. 5. Stoltzfus RJ. Iron deficiency: Global prevalence and consequences. Food Nutr Bull. 2003;24:S99–S103. 6. Hare GMT, Baker JE, Pavenski K. Assessment and treatment of preoperative anemia. Can J Anaesth. 2011;58:569–581. 7. Freedman J, Luke K, Escobar M, et al. Experience of a network of transfusion coordinators for blood conservation (ONTraC). Transfusion. 2008;48:237–250.

8. Tsui AK, Dattani ND, Marsden PA, et al. Reassessing the risk of hemodilutional anemia: Some new pieces to an old puzzle. Can J Anaesth. 2010;57:779–791. 9. Pasricha SR, Flecknoe-Brown SC, Allen KJ, et al. Diagnosis and management of iron deficiency anaemia: A clinical update. Med J Aust. 2010;193:525–532. See Also (Topic, Algorithm, Electronic Media Element) • Blood oxygen carrying capacity • Mixed venous oxygen saturation • Transfusion related lung injury (TRALI) • Transfusion infections

CODES ICD9 • 280.9 Iron deficiency anemia, unspecified • 284.9 Aplastic anemia, unspecified • 285.9 Anemia, unspecified ICD10 • D50.9 Iron deficiency anemia, unspecified • D61.9 Aplastic anemia, unspecified • D64.9 Anemia, unspecified

CLINICAL PEARLS

• Transfuse actively bleeding patients more aggressively than non-bleeding patients • Use all aspects of clinical analysis to support your decision to transfuse • Treat and diagnose anemia prior to elective surgery to avoid risk of anemia and transfusion

ANEMIA OF PREMATURITY Alberto J. De Armendi, MD, AM, MBA Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• The physiologic nadir of hemoglobin in newborns occurs at 8–12 weeks. It is the result of a decrease in erythropoietin in response to the transition from a relatively hypoxic state in utero to a hyperoxic state in room air. It is usually asymptomatic and gradually increases to adult values within the first 2 years of birth. • Anemia of prematurity (AOP), however, is a pathologic and exaggerated response to decreased erythropoietin seen in premature infants (<37 weeks). – Reduced hemoglobin, with lowest hemoglobin levels 6–7 g/dL in extremely low birth weight (ELBW) infants – Signs and symptoms of anemia manifest – Independent risk factor related to apnea – Spontaneous resolution by 6 months of age – Starts earlier and lasts longer than in normal newborns – Normocytic and normochromic red blood cells (RBCs) • This patient population is at-risk for several other causes of anemia, including shortened RBC life span and enhanced blood loss. Thus, the premature infant’s impaired ability to increase erythropoietin levels further compounds the levels of anemia. EPIDEMIOLOGY Incidence

• Inversely proportional to: – Gestational age – Birth weight • Advancements in technology have resulted in a new group of preterm infants that previously could not survive; thus increasing the incidence of AOP. Prevalence

• No sex prevalence • No race prevalence

Morbidity

• Secondary to transfusions: Immune-related and infectious • Apnea • Poor feeding/decreased weight gain

Mortality

In general, mortality is increased in premature infants 42 per 1,000 (compared to term infants 1.8 per 1,000) ETIOLOGY/RISK FACTORS

• Decreased RBC production that can be associated with prematurity (1,3,4). – Inadequate synthesis of erythropoietin in response to hypoxia that results in suboptimal erythropoiesis. – Nutritional deficiencies: Iron, folate, protein, B12 • Decreased RBC life span that can be associated with prematurity (increased destruction): – Immune hemolytic anemia: Rh or ABO incompatibility, maternal autoimmune disorders, drug-induced – Enzyme abnormalities: Glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency – RBC membrane defects: Spherocytosis, stomatocytosis – Hemoglobinopathies: Thalassemia • Increased blood loss that can be associated with prematurity – Frequent laboratory testing in critically ill infants (iatrogenic) can exacerbate AOP and increase the need for transfusions. – Fetomaternal or fetoplacental hemorrhage – Placenta previa, placental abruption – Internal bleeding: Intracranial, intra-abdominal, pulmonary

PATHOPHYSIOLOGY

• The fetal environment has several adaptations to accommodate the degree of hypoxia and maximize oxygen delivery to the brain and heart (3,5). – Hypoxic pulmonary vasoconstriction is maintained through decreased production of nitric oxide (minimal pulmonary blood flow with oxygenation and ventilation occurring at the placenta). – High pulmonary artery pressures lead to high right heart pressures. This maintains the right-to-left shunt through the foramen ovale (FO). – Increased circulating prostaglandins that maintain the patency of the ductus arteriosus (DA) and the ductus venosus (DV). – Fetal hemoglobin has a strong affinity for oxygen to facilitate efficient extraction across the placenta. The P50 is ∼19 mm Hg, compared to adult hemoglobin (∼27 mm Hg). • Transition to the extrauterine environment involves decreased shunting secondary to increased oxygen tensions and rapid right and left heart pressure changes. With the neonate’s first several breaths, circulating oxygen tensions rise rapidly with resultant increases in bradykinin and nitric oxide and decreased pulmonary vascular resistance; blood flow increases through the pulmonary vasculature. Additionally, circulating prostaglandins decrease rapidly and result in closure of the ductus arteriosus. The relatively hyperoxic environment suppresses erythropoietin production (3). • Erythropoietin: In utero, it is produced by the liver and kidneys in response to transcription factor hypoxia inducible factor-1 (HIF-1). In the premature infant, it is believed that there is a relative insensitivity by the hepatic oxygen sensor to hypoxia and anemia, resulting in inadequate synthesis of HIF-1.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Delay surgery, if possible. When surgery must proceed, consider blood transfusion prior to arrival to the operating room or during the case. Type and cross matched, leukocytereduced, and CMV-negative blood should be administered. • Minimize laboratory blood draws to those absolutely needed; additionally, decrease the volume drawn • Maintain a thermoneutral environment. The combination of cold and hypoxia can result in patent ductus arteriosus (PDA) shunting.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Apnea • Poor weight gain • Difficulty feeding • Decreased activity

History

• Apnea history • Feeding history • Weight gain history • Retinopathy of prematurity (ROP)

Signs/Physical Exam • Tachypnea • Tachycardia • Pallor • Decreased activity • Flow murmurs • Distended abdomen

TREATMENT HISTORY

• Transfusions: Indications and guidelines are nonspecific, including hemoglobin levels, apnea, bradycardia, poor weight gain, ventilator needs. Packed RBCs should be CMVnegative and leukocyte-reduced. • Placental RBC transfusion: Umbilical cord blood may decrease the need for non-autologous blood transfusion. However, studies cite limitations to this method, such as insufficient volumes collected, clotting, hemolysis, contamination, and cost. • Reduced RBC drawing and utilization of tubes with fill-lines (allow close approximation of the volumes needed for testing) • Observation

MEDICATIONS

• Supplemental vitamins

– Iron – Vitamin E – Vitamin B12 – Folic acid • Recombinant erythropoietin: The primary pathophysiology of AOP is an impaired ability to increase erythropoietin production; thus, exogenous administration can be an effective therapeutic modality. Studies have suggested that when administered early, it can reduce the use of RBC transfusion. However, concerns have been raised that there is an increased incidence of ROP.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

Hemoglobin/hematocrit levels

CONCOMITANT ORGAN DYSFUNCTION Issues with prematurity, including

• Neurologic: Intraventricular hemorrhage, hydrocephalus • Retinopathy of prematurity • Cardiac: PDA • Respiratory: Bronchopulmonary dysplasia, respiratory distress requiring ventilatory support, apnea of prematurity • Gastrointestinal: Necrotizing enterocolitis, perforation, inguinal hernia (incarceration), history of re-anastomosis or fundoplication • Sepsis

CIRCUMSTANCES TO DELAY/ CONDITIONS

Need optimization of hemoglobin/hematocrit prior to arrival in the operating room. CLASSIFICATIONS

Gestational age and birth weight are indirectly related to occurrence of AOP. • Low birth weight (LBW): <2,500 g, 36–37 weeks gestational age • Very low birth weight (VLBW): <1,500 g, 31–36 weeks gestational age • ELBW: <1,000 g, 24–30 weeks gestational age

TREATMENT PREOPERATIVE PREPARATION Premedications

• Blood transfusion, as appropriate • May give atropine (20 mcg/kg) to prophylax against bradycardia

Special Concerns for Informed Consent

• Parental consultation for postoperative ventilatory support

• Risk of hypothermia, ROP, blood transfusions

INTRAOPERATIVE CARE Choice of Anesthesia

Dependent on surgical procedure Monitors

• Standard ASA monitors, with 2 pulse oximeters for preductal and postductal measurements • Precordial stethoscope • Urinary Foley catheter may be considered when blood transfusion is expected.

Induction/Airway Management

Majority of cases will arrive intubated to the OR. Maintenance

• Avoid hypoxia, hypothermia, and increased airway pressures that can increase pulmonary vascular pressures and favor right-to-left shunting. • Avoid administering high FIO2 (retinopathy of prematurity) Extubation/Emergence

Patients who were intubated on arrival will usually return to the neonatal intensive care unit (NICU) intubated.

POSTOPERATIVE CARE BED ACUITY NICU

MEDICATIONS/LAB STUDIES/CONSULTS

• Iron • Caffeine 10 mg/kg (2) • Minimal laboratory requirements except monitoring of hemoglobin levels

COMPLICATIONS

• Transfusion related: – Fluid overload – Electrolyte imbalance – Hypothermia – Infectious – Immune-related

REFERENCES

1. Peiris K, Fell D. The prematurely born infant and anesthesia: Continuing education in anaesthesia. Crit Care Pain. 2009;9(3):73–77.

2. Welborn LG, Greenspan JC. Anesthesia and apnea: Perioperative considerations in the former preterm infant. Pediatr Clin North Am. 1994;41(1):181–198.

3. Aher S, Malwatkar K, Kadam S. Neonatal anemia. Semin Fetal Neonatal Med. 2008;13(4):239–247. 4. Salsbury DC. Anemia of prematurity. Neonatal Netw. 2001;20(5):13–20.

5. Widness JA. Pathophysiology of anemia during the neonatal period, including anemia of prematurity. Neoreviews. 2008;9(11):e520.

ADDITIONAL READING

• Ohisson A, Aher SM. Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2006;3:CD004863.

See Also (Topic, Algorithm, Electronic Media Element) • Retinopathy of prematurity • Hemoglobin

CODES ICD9 776.6 Anemia of prematurity ICD10 P61.2 Anemia of prematurity

CLINICAL PEARLS

• Anemia of prematurity is the result of impaired erythropoietin production in response to anemia and tissue hypoxia. Additionally, in premature infants, the concomitant increase in RBC destruction and shortened lifespan can further exacerbate the anemia.

ANESTHESIA FOR NEURORADIOLOGY Eman Nada, MD, PhD

BASICS DESCRIPTION General

• Advancement in imaging technology and the growing field of interventional neuroradiology have increased the need for anesthesia services in the “out-of-OR” setting. However, several challenges exist: – Radiation exposure hazards: Early effects of ionizing radiation are dose-dependent and risk increases with increased radiation dose (may occur many years after exposure). – Special OR setup: Suites are often crowded by large radiology equipments that are difficult to move; the anesthesia space is usually small; large radiation protective shields and heavy aprons can make movement and access to the patient difficult; the airway can be distant from the machine and anaesthetist; the room is dark; and paramedical personnel are not familiar with anesthesia support (experienced help is often remote). – MRI hazards: Ferrometallic materials can be projectile and may cause accidents; electric noise can distort monitored waveforms; acoustic noise may present a distraction; electromagnetic waves can cause patient burns in areas of contact with monitor cords or in the presence of metallic implants; and in an emergency situation it takes 90 seconds to retract the magnet tube and have a crash cart in the room (patient may need to be removed from the room). • Angiographic interventions can be broadly classified as those that: – Obliterate the lumen. Embolization of cerebral and dural arteriovenous malformation (AVM), vessel-feeding tumors, cerebral aneurysms, and fistulae. – Open the lumen and revascularize. Angioplasty of atherosclerotic lesions and thrombolysis or thrombectomy of acute thromboembolic stroke. • Intraoperative magnetic resonance imaging system (IMRIS) is used for the: – Resection of brain tumors – Implantation of deep brain stimulators (DBS) and electroencephalographic (EEG) electrodes • Anesthesia is usually requested for diagnostic procedures in: – Pediatric patients – Uncooperative or claustrophobic patients – Patients with complex medical problems when strict hemodynamic monitoring is needed Position

• Diagnostic and interventional angiographic procedures: Supine with arms tucked • Intraoperative MRI: Supine, prone, lateral, and semi-sitting position have been reported.

Incision

• Diagnostic and interventional procedures: Typically via femoral catheterization; however, carotid or brachial arteries may be utilized. • Intraoperative MRI: Craniotomy incision

Approximate Time

• Diagnostic: ∼30–60 minutes • Angiographic interventional procedures: ∼4–6 hours • Intraoperative MRI: ∼4–6 hours

EBL Expected

• Diagnostic and interventional angiographic procedures: None to minimal • Intraoperative MRI: ∼50–500 mL, depending on the location and size of the lesion, and complexity of the procedure

Hospital Stay

Diagnostic procedures: Out-patient or in-patient Special Equipment for Surgery

• Contrast material • Endovascular catheters to deliver coils, detachable balloons, and embolizing agents • MRI suite specially equipped to provide surgery with compatible anesthesia machines, monitors, and other equipments

EPIDEMIOLOGY Incidence

• In 2009, an estimated 40,663 cerebral angiograms, 109,000 angioplastic carotid endarterectomies, and 700,000 endovascular aneurysmal repairs were performed. • In 2010, ∼1,047 neuro interventional MRI procedures were performed; this is a 300% increase over 5 years since its start.

Morbidity

See “Complications” Mortality

IV contrast: 1 out of 170,000 reactions

ANESTHETIC GOALS/GUIDING PRINCIPLES

• A full preoperative evaluation should be performed even in patients receiving deep sedation/analgesia for diagnostic procedures. • Out-of-OR standards are necessary for the safe delivery of anesthesia. They include: – A reliable source of oxygen with a back-up – Airway equipment (e.g., Ambu bag) – Standard ASA monitors – Suction – Waste gas scavenger if volatile agents are administered

– Anesthetic drugs and emergency drugs – Sufficient space – Means to provide cardiopulmonary resuscitation – Sufficient safe electrical outlets – Adequate illumination with battery-powered backup • Maintain a still field as well as a patent airway and hemodynamic stability

PREOPERATIVE ASSESSMENT SYMPTOMS

Depends on diagnosis or indication History

• NPO status • Shellfish, iodine, IV contrast, or protamine reactions • Ability to lie flat, snoring, sleep apnea • Acquired or implanted metallic devices, extensive tattoos, permanent eye make-up

Signs/Physical Exam

• Depends on diagnosis or indication and can include a baseline-focused neurologic exam, Glasgow Coma Scale, disease-specific scoring system (Hunt Hess for subarachnoid hemorrhage and NIHSS for stroke) • General medical and airway exam

MEDICATIONS

• Interventional procedures: Antiplatelets, anticoagulants; calcium channel blockers for cerebral protection or reducing vasospasm; triple H therapy for prophylaxis or treatment of vasospasm (induced hypertension, hemodilution, hypervolemia) • Intraoperative MRI: Steroids, diuretics, anticonvulsants • Pain medications: For headache, surgical pain in iMRI procedures • Medications specific to the patient’s co-morbidities

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• BUN/Cr is often attained prior to IV contrast. • Depends on comorbidities

CONCOMITANT ORGAN DYSFUNCTION Depends on procedure indication

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis as needed; caution or avoidance in elderly or altered patients as well as epileptic patients for EEG electrode implantation • Stroked patients may present with a full stomach; gastric acid and volume-reducing medications should be considered. • Parkinsonian patients scheduled for DBS should have their morning dopaminergic and anticholinergic medications held. • Tumor patients may require re-dosing of steroids or antiepileptics. • Corticosteroids and possibly an antihistamine may decrease the incidence of contrast reactions in “at-risk” patients. • Radiation safety: Lead aprons, thyroid shields, and protective eye goggles should be considered, as appropriate, for the patient (as well as the anesthesia provider!) • Setup should be meticulous due to the difficulties encountered with patient manipulation once the procedure has begun.

Special Concerns for Informed Consent

• Pediatric patients require parent consent. • Uncooperative or altered patients require a family member or power of attorney consent.

Antibiotics/Common Organisms

• Diagnostic and interventional angiographic procedures: Usually considered clean procedures; antibiotics are given only in high-risk procedures. • Intraoperative MRI: Skin organisms, third-generation cephalosporins are usually given.

INTRAOPERATIVE CARE Choice of Anesthesia

• Diagnostic procedures may need minimal or conscious sedation and can be performed by non-anaesthetists certified in administering sedation. Anesthesia care providers are often called upon to provide deep sedation/analgesia or general anesthesia; the choice is based upon the procedure, positioning, comorbidities, access/nearness to the patient, and ease of ventilation or intubation in the event that the patient obstructs or becomes apneic. • Interventional: Typically general anesthesia; deep sedation/analgesia is used in some revascularization procedures. • Intraoperative MRI: GA. Awake craniotomy is sometimes needed to resect a tumor under MRI near eloquent area.

Monitors

• Standard ASA monitors • Intra-arterial pressure monitoring for interventional procedures and intraoperative MRIs • Neurophysiologic-evoked potential monitoring in some spinal cord pathology embolization procedures • Intracranial pressure (ICP) monitoring • Activated clotting time (ACT) • Neuromuscular twitch monitor • Neurologic exam in patients under MAC • Foley catheter to measure urine output

• Oropharyngeal temperature probes will interfere with the angiography pictures; axillary or skin probes are better options. In IMRIS a fiberoptic probe can be used in the groin.

Induction/Airway Management

• Be prepared to induce anesthesia and manage the airway in a less than optimal position. • Extra-long breathing tubes and infusion lines are needed because anesthetic equipments are often relocated after induction to allow for imaging equipment to move freely or to move to safer magnetic fields in MRI scanners. • Some iMRI suites have an induction room outside the scanner. This provides free access to all anesthesia equipments at induction; the patient is then transported with assisted/controlled ventilation (Ambu bag, Bain circuit) to the scanner. • An ETT with muscle relaxation can provide a more secure and controllable airway, along with extreme immobilization compared to an LMA.

Maintenance

• Pressure points are secured meticulously since the patient is going to be covered and arms tucked with limited access. • Renal protection for contrast: No proven strategy is agreed upon; preoperative hydration for impaired renal function is usually used. Approximately 2/3rd of the severe and fatal contrast reactions occur within the first several minutes. • Heparinization is required whenever catheters are introduced into blood vessels. ACT monitoring is utilized to guide therapy. Protamine should be standby whenever heparin is used. • Antiplatelets are used by the neurointerventionalist after the procedure.

Extubation/Emergence

• Avoid patient coughing, bucking, or straining which can cause hypertension and increased ICP. • Patient should be awake enough to have a neurologic exam.

POSTOPERATIVE CARE

• May require transport over long distances to the postanesthesia care unit (PACU); monitors, supplemental oxygenation, airway equipment, and emergency drugs should be considered as appropriate. • Standard PACU evaluation, care, and discharge criteria • No flexion at the groin for a few hours after femoral groin access is removed; consider reverse Trendelenburg positioning if “head up" is needed.

BED ACUITY Variable

ANALGESIA

• Interventional radiologic procedures are usually not painful, and local anesthetics are injected at the access site. • Short-acting narcotics are often preferable to longer-acting narcotics.

COMPLICATIONS

• Vascular perforation of the access site • Obliteration of the wrong vessel • Contrast dye reactions can range from mild symptoms such as scattered urticaria and pruritus to laryngeal edema, life-threatening arrhythmias, hypotension, bronchospasm, pulmonary edema, seizures, syncope, and even death. Nonionic contrast media has been shown to decrease the incidence significantly. • Contrast nephropathy: Usually occurs at 1–3 days after contrast injection. Patients at increased risk include pre-existing renal disease, volume depletion, high or repeat doses of contrast, and administration of other nephrotoxic drugs. Use of oral or IV theophylline, acetylcysteine, fenoldapam, statins, or bosentan (an endothelin antagonist) have not shown consistent efficacy against renal insult.

PROGNOSIS

Variable depending on the preoperative morbidity, the underlying pathology, site and extent of procedure

REFERENCES

1. Bergese SD, Puente EG. Anesthesia in the intraoperative MRI environment. Neurosurg Clin N Am. 2009;20:155–162.

2. Cloft HJ, Rubenstein A, Lanzino G, et al. Intra-arterial stroke therapy: An assessment of demand and available work force. AJNR Am J Neuroradiol. 2009;30:453–458. 3. Gasser T, Senft C, Rathert J, et al. The combination of semi-sitting position and intraoperative MRI—first report on feasibility. Acta Neurochir (Wien). 2010;152:947–951. 4. Qureshi AI. Ten years of advances in neuroendovascular procedures. J Endovasc Ther. 2004;11(Suppl 2):II1–II4. 5. Siddiqi N. Contrast medium reactions. Available at: http://emedicine.medscape.com/article/422855-overview 6. US Department of Health and Human Services. Agency of Human Health care and Quality. http://hcupnet.ahrq.gov/ See Also (Topic, Algorithm, Electronic Media Element) • Cerebral embolization • Craniotomy, awake • Radiation safety • Perioperative statins

CLINICAL PEARLS

• The anesthesia provider should not forget to wear radiation protective lead before they engage in work with challenging cases. • Anticipate potential complications and ensure appropriate anesthetic equipment setup. • Continuous infusion of muscle relaxant under GA will help provide a motionless patient for

embolization or revascularization. • For resection of tumors near eloquent areas, sedation or an “asleep-awake-asleep" technique may be utilized.

ANGIOTENSIN

Zhuang-Ting Fang, MD, MSPH

BASICS DESCRIPTION

• Angiotensin is: – A natural hormone that is part of the renin-angiotensin-aldosterone system (RAAS) – Stimulated in response to acute, sustained decreases in arterial pressure and enhanced sympathetic outflow – A direct, potent arteriolar vasoconstrictor (angiotensin II) – Responsible for stimulating the adrenal cortex to release aldosterone • Medications targeting either angiotensin receptors or angiotensin-converting enzymes (ACE) have been developed for the treatment of hypertension (HTN) and have major implications for anesthetic management. PHYSIOLOGY PRINCIPLES

• The body has 3 control systems to regulate arterial blood pressure: – “Immediate control:” The autonomic nervous system reflexes are capable of minute-tominute control of blood pressure. – “Intermediate control:” Renin and angiotensin – “Long-term control:” Occurs hours after the decrease in blood pressure by altering the sodium and water balance. This process is mediated by aldosterone with the aim of restoring blood pressure to a normal level. • Renin – Synthesized and stored in the juxtaglomerular cells in the wall of the renal afferent arterioles – Stimulated by a decrease in renal perfusion pressure associated with dehydration, acute hemorrhage, renal artery stenosis, or chronic hyponatremia – Converts circulating angiotensinogen to form angiotensin I • Angiotensinogen is synthesized in the liver and released into the plasma. • Angiotensin I – Decapeptide prohormone – Not all angiotensin I comes from conversion of angiotensinogen by renin; it is also generated by the vascular endothelium. • Angiotensin II – Octapeptide – Not all angiotensin II comes from conversion of angiotensin I by ACE; it is also generated by the vascular endothelium. – Plasma half-life is about 50 seconds and is cleared rapidly by a variety of enzymes, namely angiotensinases, in the circulation. – Has significant physiological activity on the:

Cardiovascular system: Angiotensin II binds to angiotensin AT1 receptor (a G proteincoupled receptor) on the vascular smooth muscle, leading to vasoconstriction of the precapillary arterioles and postcapillary venules. It is 40 times more potent than norepinephrine, which makes angiotensin II the most powerful endogenous vasoconstrictor. This effect is most profound in the skin, splanchnic vasculature, and kidneys, and can lead to significant decreases in blood flow to these organs. Coronary artery and cerebral artery (to a lesser extent) are also decreased. These pressor responses do not lead to a reflex bradycardia since angiotensin II acts centrally to reset the baroreceptor reflex to a higher pressure. The direct mitogenic effect of angiotensin II on cardiac cells affects cardiac remodeling, and may increase myocardial contractility and lead to hypertrophy from chronic stimulation. Central nervous system: Angiotensin II acts on the medullary vasomotor center leading to sustained HTN. It can also enhance the release of vasopressin and adrenocorticotropic hormone (ACTH) as well as regulate prolactin release in the pituitary gland. Peripheral autonomic nervous system: Angiotensin can stimulate the chromaffin cells in the adrenal medulla to release catecholamines, which is the underlying mechanism for marked HTN associated with pheochromocytoma. Adrenal cortex: Angiotensin can stimulate the synthesis and secretion of aldosterone from the adrenal cortex, leading to the retention of sodium and excretion of potassium and hydrogen in the kidneys. – It regulates ovulation and hormone production in the ovary and hormone production in the testes. It may be partially responsible for preeclamptic symptoms.

ANATOMY

• Kidneys: Produce renin • Liver: Produces angiotensinogen. • Vascular endothelium: Produces angiotensin (90% of angiotensin I and 64% of angiotensin II are generated within endothelium). • Lungs: Contain the highest concentration of ACE (peptidyl dipeptidase)

DISEASE/PATHOPHYSIOLOGY

• Hypertension: Elevated levels of renin and angiotensin lead to increased vascular resistance; this is considered as one of the mechanisms responsible for idiopathic HTN. • Coronary artery disease: In patients with HTN, the incidence of myocardial infarction was independently associated with the plasma renin activity. The growth effects of angiotensin II may play an important role in the development of coronary artery atherosclerosis and peripheral vascular disease. • Cardiac hypertrophy: Is caused not only by the increased cardiac workload from HTN, but also the mitogenic effect of angiotensin II on the cardiac muscle cells (plays a role in myocardial remodeling). • Renin-secreting tumors • Angiotensinogen-secreting tumors

PERIOPERATIVE RELEVANCE

• ACE inhibitors (ACE-I) or angiotensin receptor antagonists/blockers (ARBs) are commonly

used drugs in the treatment of HTN, chronic heart failure, or diabetic nephropathy. – Heart rate: Minimal effect – Contractility: Reflexive increase – Cardiac output: Indirect increase – Blood pressure: Decrease – Systemic and pulmonary vascular resistance: Direct decrease – Preload: Decrease – Renovascular resistance: Decrease – Natriuresis: Increase • Side effects and adverse events: – Profound and prolonged hypotension: The RAAS is responsible for restoring normotension during surgery, especially in a state of hypovolemia and decreased vascular resistance. Patients taking ACE inhibitors or angiotensin receptor antagonists preoperatively may develop profound and prolonged hypotension from the blockage of this physiologic response during surgery. Whether patients on ACE inhibitors or angiotensin receptor antagonists should discontinue the medication preoperatively remains controversial. – Persistent, dry cough and angioedema from increased kinins; it appears that there is a decreased incidence with ARBs. – Hyperkalemia from decreased aldosterone – Exacerbates renal failure in renal artery stenosis, and vasoconstricts the efferent arterioles of the glomeruli resulting in an increased glomerular filtration rate (GFR) – Angiotensin “escape:” Not all angiotensin arises from the RAAS system. ACE is contained the heart and blood vessels where it can exert harmful local effects. – Pregnancy: May cause congenital malformations and fetal abnormalities • Benefits: May decrease the degree of vasoconstriction from increased sympathetic tone caused by intraoperative surgical stress; therefore, it may potentially improve perfusion of the vital organs and maintain their normal function.

REFERENCES

1. Colson P, Ryckwaert F, Coriat P. Review article: Renin angiotensin system antagonists and anesthesia. Anesth Analg. 1999;89:1143–1155. 2. Sarkar P, Nicholson G, Hall G. Brief review: Angiotensin converting enzyme inhibitors and angioedema—anesthetic implications. Can J Anesth. 2006;53(10):994–1003. See Also (Topic, Algorithm, Electronic Media Element) • Hypertension • ACE inhibitors and hypotension • Hypotension • Chronic angina

CLINICAL PEARLS

• Angiotensin is an endogenous hormone that is part of the renin–angiotensin–aldosterone system. Its role has been exploited pharmacologically for the treatment of hypertension.

• Patients on ACE-I and ARBs may have an increased risk of refractory hypotension perioperatively. However, this has been challenged, and there are currently no guidelines based upon strong evidence for the preoperative management of these long-term medications.

ANION GAP

J. Andrew Dziewit, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION • Anion gap (AG) = [(Na+ + K+) – (Cl− + HCO3−)]; normal 7–14 mEq/L

• In metabolic acidosis, the concept of the AG is utilized to assist with the differential diagnosis. It functions to distinguish acidosis as either an: – Increase in total body acids (HCO3− anion is titrated by H+); or a – Decrease in total body HCO3− (abnormal loss from the body).

– In both scenarios, HCO3− is reduced; a calculation of the AG aids in determining which of

these 2 mechanisms is responsible. • The term “gap” does not imply that anions are missing, but only that they are not directly measured. By applying the concept that the serum is electrically neutral, measurable values for major cations and anions allow for unmeasured anions to be calculated. • Unmeasured anions include phosphates (PO4−) and sulfates (SO4−) as well as lactates, ketoacids, and toxins. Their corresponding cation (H+) dissociates and is titrated by HCO3− or other buffering systems, or it increases the acid:base ratio (causing a metabolic acidosis).

PHYSIOLOGY PRINCIPLES

• The anions of organic and inorganic acids are not easily or routinely measured. However, it is possible to measure serum Na+ and K+ (cations) and Cl− and HCO3− (anions) and “calculate” the AG: [(Na+ + K+) – (Cl− + HCO3−)]. Or, AG = measured cations –

measured anions; potassium may be excluded. • Normally, the serum AG is determined by negative charges on serum proteins, particularly albumin. • Metabolism results in the production of volatile, organic, and inorganic acids. – Volatile acids: Carbon dioxide (CO2) is a byproduct of sugar, fat, and amino acid metabolism. Basal CO2 production is approximately 12,000 mmols/d and is

exhaled/excreted by the lungs, as well as buffered by the bicarbonate system. – Inorganic acids: Sulfate and phosphates are byproducts of amino acid metabolism; basal production is approximately 50–100 mEq/d. Excretion occurs renally. – Organic acids: Lactate and ketones. Lactate is produced via anaerobic metabolism. Ketones result from fatty acid breakdown when insulin is not present via a beta-oxidizing process. Both are excreted by the liver and kidneys. • HCO3− is ubiquitous in the body and exists in equilibrium between the intravascular and

extracellular compartments. It is present in the stool and carefully regulated by the renal tubules.

DISEASE/PATHOPHYSIOLOGY

• High AG metabolic acidosis: – Results from an increase in an acid molecule’s corresponding anion; thus represents increased total body acid. – Acids are composed of a cation (H+) and an anion (A−). – In solution, the acid compound (HA) dissociates into a H+ and its corresponding anion (HA ←→ H+ + A−). – The H+ is buffered by one of the body’s buffering systems, including bicarbonate (H+ + HCO3− ←→ H2CO3 ←→ H2O + CO2) in order to “cushion” or decrease adverse effects of the acid load. – However, this “titration” results in a reduction in HCO3− values; when the acid load

exceeds the buffering capacity, acidosis manifests. – Electroneutrality is maintained during this titration process (H+ cation plus a HCO3−

anion). There is no increase or decrease in positive- or negative-charged molecules. – Increased acid production can result from anaerobic metabolism (lactic acidosis), ketone production (diabetic ketoacidosis), toxins (methylene, ethanol, salicylates), and hyperosmolar hyperglycemia. – Reduced acid excretion can result from impaired renal function (uremia). • Normal AG metabolic acidosis: – Loss of HCO3− (or bicarbonate precursors) from the body results in an increase in the

acid:base ratio. – There is no increase in total body acid, and hence no increase in anions. – In order to maintain electroneutrality, a loss in HCO3− is balanced by a “gain” in Cl−; this

results in a hyperchloremic state. – HCO3− can be lost by diarrhea, renal tubular acidosis, carbonic anhydrase inhibitors,

ureteral diversion, and intestinal losses; additionally, hyperchloremic crystalloid solutions (normal saline, [Cl−] 154 mEq/L) serve to dilute the bicarbonate concentration as well as increase the chloride concentration (resulting in renal excretion of bicarbonate). • Low AG is a less commonly utilized term that describes low albumin states. Albumin is a negatively charged protein and its loss from the serum results in the retention of other negatively charged ions such as chloride and bicarbonate. Because they are utilized in the calculations, there is a decrease in the gap. AG falls by 2.3–2.5 mEq/L for every 1 g/dL reduction in serum albumin concentration.

PERIOPERATIVE RELEVANCE

• Base excess is more frequently utilized than the AG in the perioperative period. This is because metabolic acidosis is often the result of lactic acidosis secondary to anaerobic metabolism. – Lactic acidosis indicates that there is tissue hypoxia either from hypovolemia,

hypoperfusion, hypovolemia, or hypotension. – Perioperatively, this can result from surgical blood loss; evaporative/insensible losses; episodes of hypoxia at induction, intraoperatively, or at emergence; anemia; or hypotension. – Base excess is useful in determining the extent of the increased acid load, as opposed to aiding in the differential diagnosis. • The AG can be implemented perioperatively to determine if the metabolic acidosis is secondary to a hyperchloremic non-AG acidosis. This can manifest from as little as 2 L of normal saline solution. Na+ 154 mEq/L is balanced by Cl− 154 mEq/L. The chloride concentration is not physiologic and initially results in the dilution of HCO3−. Ultimately, however, HCO3− anion is eliminated by the kidneys in order to maintain electroneutrality

(increased chloride anion load). Clinical consequences of the metabolic acidosis are unclear. However, attempts at correcting the abnormality may actually cause more issues (iatrogenic causes such as administering additional hyperchloremic crystalloids). • In the ICU and at the bedside, the AG can provide a clinically useful tool to identify one of the many causes of metabolic acidosis in the critically ill, especially when hypoalbuminemia and lactate are considered. Additionally, it can be utilized to monitor, assess, and guide therapy during sepsis. • Ketoacidosis: The measured AG disturbance is often less than expected from the fall in serum bicarbonate. This results from the renal loss of ketoacid anions (beta hydroxyl butyrate) that accompany sodium and potassium salt excretion. • Multiple myeloma results in a pathologic increase in cations that are not measured; IgG paraproteinemia causes a reduced AG. • Postcardiac surgery metabolic acidosis is typically the result of an increase in unmeasured acids, and less commonly from lactic acidosis. – Cardiopulmonary bypass (CPB) circuits are usually primed with 1.4–2 L of hyperchloremic crystalloid. – ABG taken immediately after “going on pump” demonstrates a non-AG metabolic acidosis. – More frequent in children due to the ratio of CPB priming fluid to smaller blood volumes (even with low-volume priming) – This acidosis is transient and lasts <24 hours.

EQUATIONS

• AG = [(Na+ + K+) – (Cl− + HCO3−)] • AG corrected (for albumin) = calculated AG + 2.5 (normal albumin g/dL – observed albumin g/dL)

REFERENCES

1. Chawla LS, Shih S, Davidson D, et al. Anion gap, anion gap corrected for albumin, base deficit and unmeasured anions in critically ill patients: Implications on the assessment of metabolic acidosis and the diagnosis of hyperlactatemia. BMC Emerg Med. 2008;8(18). 2. ernon C, Letourneau JL. Lactic acidosis: Recognition, kinetics, and associated prognosis. Crit Care Clin. 2010;26(2):255–282.

3. Liamis G, Milionis HJ, Elisaf M. Pharmacologically-induced metabolic acidosis: A review. Drug Saf. 2010;33(5):371–391. 4. Filipescu D, Raileanu I, Luchian M, et al. Hyperchloremic metabolic acidosis after cardiac surgery. Crit Care. 2006;10(Suppl1):P200. 5. Murray DM, Olhsson V, Fraser JI. Defining acidosis in postoperative cardiac patients using Stewart’s method of strong ion difference. Pediatr Crit Care Med. 2004;5(3):240–245.

6. Liskaser FJ, Bellomo R, Hayhoe M, et al. Role of pump prime in etiology and pathogenesis of cardiopulmonary bypass-associated acidosis. Anesthesiology. 2000;93(5):1170–1173.

ADDITIONAL READING

• Ishihara K, Szerlip HM. Anion gap acidosis. Semin Nephrol. 1998;18(1):83–97. • Lim S. Metabolic acidosis. Acta Med Indonesia. 2007;39(3):145–150.

See Also (Topic, Algorithm, Electronic Media Element) • Metabolic acidosis • Diabetic ketoacidosis • Carbon dioxide transport • Lactic acidosis

CLINICAL PEARLS

• Anion gap represents the difference in charge between measured cations and measured anions. • “Missing” negative charge is composed of weak acids (A−) like albumin and phosphate and strong unmeasured anions such as lactate. • Frequent causes of an elevated anion gap metabolic acidosis are represented by the mnemonic MUDPILES: – Methanol – Uremia – Diabetic ketoacidosis – Paraldehyde – Iron, isoniazid (INH) – Lactic acid – Ethanol, ethylene glycol – Salicylates • Frequent causes of a normal anion gap metabolic acidosis are represented by the mnemonic USEDCARP: – Ureterostomy – Small bowel fistula – Extra chloride – Diarrhea – Carbonic anhydrase inhibitors (acetazolamide) – Adrenal insufficiency – RTA

– Pancreatic fistula

ANTERIOR CERVICAL DISCECTOMY AND FUSION (ACDF) Nina Singh-Radcliff, MD Chris A. Steel, MD

BASICS DESCRIPTION General

• Removal of a herniated or degenerative disc that is compressing on the cervical spine – A herniated disk refers to the gel-like material either bulging or rupturing through a weak area in the surrounding wall (annulus). Irritation and swelling occurs when this material squeezes out and presses on a nerve. – Degenerative disc disease refers to the drying out of the disc, resulting in shrinkage and loss of flexibility and cushioning properties (increases with age). Osteophytes (bone spurs) result from wear, damage, and inflammation. These changes can result in spinal cord compression, or myelopathy. • After induction and intubation, the neck is prepped; the anterior approach allows access to the disc without disturbing the spinal cord, spinal nerves, and strong neck muscles of the back. If an autograft will be utilized for fusion, the hip area is also prepped. • Surgical exposure involves creating an avascular dissection place or tunnel to the disc via moving aside muscles in the neck, retracting the trachea, esophagus, and arteries. • Preparation to remove the disc involves localizing the affected level and utilizing spreaders above and below to facilitate removal of the damaged disc. • Nerve decompression consists of removal of disc fragments and osteophytes (bone spurs). The annulus (outer wall of the disc) is incised, followed by removal of the disc; bone spurs are removed with a Burr (a small rotary cutting tool). A microscope is utilized to remove disc material and bone spurs near the spinal cord. The posterior longitudinal ligament (courses behind the vertebrae) is removed to reach the spinal canal and any material pressing on the nerves is removed. • A foraminotomy is then performed (the foramen through which the spinal nerve exits, is enlarged with a drill) to allow more room to exit the spinal canal. • Fusion: After the disc is removed, the space between the vertebrae is empty and a bone graft may be inserted to prevent the vertebrae from collapsing and rubbing together; serves as a bridge. To prepare the graft for fusion, the outer cortical layer of bone is roughened up until punctuate bleeding is seen. This will allow blood vessels to grow into the grafted bone. The bone graft is shaped to fit snugly into the space and is typically further immobilized and held together with a metal plate and screws (reduced incidence of bone graft migration, improved fusion). Position

Supine; shoulder roll may be utilized to enhance neck extension and exposure; arms are typically tucked to allow the surgical team to stand on both sides of the neck.

Incision

• 2–3 inches, depending upon the number of levels • Left-sided approach is preferred by some in order to reduce injury to the recurrent laryngeal nerve (RLN); the right side has a 2–3% anomalous course.

Approximate Time

1–1.5 hours per level EBL Expected

Less than 50 mL Hospital Stay

• Advocates for same-day discharge cite that the short operative time, minimal blood loss, and low risk of postoperative hematoma make it ideal in patients without significant comorbidities and good home help. May significantly reduce procedure costs. • Advocates for hospital admission cite that the need for a drain and the catastrophic risk of a postoperative neck hematoma preclude discharge home on POD 0.

Special Equipment for Surgery

• Fluoroscopy or portable x-ray • Bone graft (autologous or cadaveric) • Neuromonitoring: Computer and personnel for monitoring EMG, SSEPs, and MEPs

EPIDEMIOLOGY Incidence

150,000 per year in the US Prevalence

Increases with age, osteoporosis Morbidity

• Isolated postoperative dysphagia: 60% initially, 5% at 1 year (1) • Symptomatic RLN palsy: 3.1% • Postoperative hematoma: 1–2% • Bone graft migration: 1–2% • Dural penetration/tear, worsening or pre-existing myelopathy, Horner’s syndrome, instrumentation backout, superficial wound infection: Each less than 1%

Mortality

Rare. Esophageal perforation, retropharyngeal edema or hematoma, quadriplegia ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients have often failed a course of conservative treatment (epidural steroid injections, physical therapy, acupuncture, oral pain medications). • Airway management may be affected by a limited range of neck motion due to pain,

elicitation of myelopathy, or potential for injury. The sniffing position, or even flexion/extension, to align the oropharynx, hypopharynx, and larynx may not be possible. • Neuromonitoring. EMG, SSEPs, and MEPs require modification of anesthetic technique to optimize quality of results. • Controlled hypotension may be requested to reduce bone bleeding.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Weakness, pain, paresthesias, numbness in C2–7 distribution (neck, shoulder, arms, hand) • Arm pain often worse than neck pain

History

• No improvement with conservative therapy • Chronic pain medications: Patients may or may not have taken their scheduled doses on day before or day of surgery. • Comorbidities increase with age.

Signs/Physical Exam

• Sensory and motor deficits should be clarified and noted, including the ability to swallow and if any baseline hoarseness. • Ability to extend the neck without experiencing symptomatic spinal cord compression (Lhermitte’s phenomenon)

MEDICATIONS

Pain patches, pain medications

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Laboratory exam depends upon comorbidities. • PT/PTT/INR, if clinical history of bruising, bleeding, or drugs • MRI, CT, and myelogram are often performed prior to surgery.

CONCOMITANT ORGAN DYSFUNCTION • Osteoporosis • Chronic pain syndrome

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis and analgesia as needed; chronic pain patients may require increased dosing. • Dexamethasone 10 mg IV may be requested by some surgeons.

Special Concerns for Informed Consent

• Smoking cessation: Nicotine reduces successful fusion. • Hoarseness, swallowing difficulties postoperatively • Postoperative hematoma

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with ETT • Partial or total intravenous anesthesia (TIVA) to optimize neuromonitoring

Monitors

• EMG: Supplements visual identification to avoid RLN injury. An ETT with special electrodes that connect to a computer can measure the muscle electrical potential of the vocal cords. Because RLN stimulation causes movement of the cords, it allows the surgeon to identify and avoid inadvertent nerve injury. Must avoid NMBDs (2). • SSEPs: Assess the integrity of the posterior spinal cord. Volatile agents at a MAC >0.5 decrease the amplitude and increase the latency of the waveforms (false positive). • MEPs: Assess the integrity of the anterior spinal cord; must avoid NMBDs. • Arterial line based on comorbidities

Induction/Airway Management

• A limited range of motion (pain, myelopathy, prior fusion, stiffness) may preclude sniffing position or even flexion. Consider having a video laryngoscope, fiberoptic bronchoscopy (awake or asleep depending on ability or ease of bag mask ventilation), or other special management devices available in the event of difficulty (alternatively, may consider utilizing for initial attempts). • Consider having the patient self-position their neck while on the OR table and maintaining this position after induction; document if this is performed. • ETT cuff may increase pressure exerted on the tracheal wall and the submucosal portion of the RLN; when this is combined with surgical tissue retractors transmitting pressure through the soft tissues of the neck to the trachea, it can result in ischemic injury. Maintaining a cuff pressure <25 cm H2O to ensure adequate blood flow to the capillary beds may prevent this. Other studies have suggested the utilization of the “just seal” pressure (air is withdrawn from the ETT cuff until a leak around the cuff is detected, and subsequently reinjected slowly until an air seal is barely obtained). • Secure the ETT to the contralateral side of the incision; tape should not be attached to maxilla or mandible on the operative side. • Neuromuscular blockade cannot be utilized if EMG or MEP is performed. Succinylcholine or small intubating dose of nondepolarizing muscle relaxants may be utilized to optimize intubating conditions (opening of mouth, vocal cord aperture to pass ETT), and will wear off quickly.

Maintenance

• Confirm that the head is supported and not levitating.

• Fluoroscopy or single shots require appropriate radiation protection. • EMG, MEPs, and SSEPs, may have improved conduction with the use of partial or total intravenous drug administration. Propofol is often utilized as either the sole agent, or in conjunction with volatile, nitrous, narcotic (remifentanil, sufentanil, fentanyl), or other sedative/analgesic (dexmedetomidine, ketamine). Choice is based upon the preference or experience of the anaesthetist, surgeon, neuromonitoring team, institution’s availability, cost considerations, and patient factors. The goal is to maintain a steady state, particularly during the period where injury may occur (dissection, discectomy), and avoid bolusing (may create false positives) (3). • Critical to maintain an adequate level of anesthesia since sudden movements can result in danger to the patient (coughing, bucking, sitting up), especially since NMBDs cannot provide a layer of safety against this. Extubation/Emergence

• Avoid coughing and bucking • Consider 30° reverse Trendelenburg position to avoid passive aspiration • Neurologic exam soon after emergence • RLN injury may increase risk of aspiration and stridor.

POSTOPERATIVE CARE BED ACUITY

• Same-day discharge is practiced at some centers; however, the potential for postoperative hematoma with resultant airway compromise makes it controversial. Proponents argue that it can significantly reduce healthcare costs and there is only a minimal risk of postoperative hematoma. • Admission: Typically 1–2 days allowing for drain removal, neurologic assessment, monitoring of swallowing/hoarseness, and hematoma. On POD 0, the patient should sit up in a chair and begin supervised ambulation. • Telemetry or ICU if significant comorbidities or frequent neurologic testing needs to be done (new neurologic deficit, stridor) • Cervical collar often utilized to allow time for the bone graft to fuse

ANALGESIA

• Typically mild at the incision site. Significant pain can occur at the bone grafting site. • Persistent pain is often the result of permanent damage to the nerve making it unresponsive to decompressive surgery; spinal cord stimulators may provide relief. COMPLICATIONS

• Airway compromise: Hematoma formation may impinge on the trachea; RLN damage can cause unopposed adduction of the cricothyroid muscle resulting in stridor; a traumatic intubation or surgical trauma can cause airway edema. • Anesthesia awareness • Tongue laceration from MEPs • Hoarseness and swallowing difficulties often resolve in a few months; they persist in

~1/250 cases and require an ENT consult. • Failure to fuse: Increased in smokers (nicotine inhibits bone-growing cells), osteoporosis, obesity, and malnutrition • Hardware fracture: The metals, rods, and plates used to stabilize the spine may move or break before the vertebrae are completely fused. Requires surgery to remediate. • Bone graft migration: Movement from the correct position. Occurs soon after surgery and more likely if hardware is not utilized to secure the graft or if multiple levels are fused. Requires surgery to remediate. • Transitional syndrome, also known as adjacent-segment disease: Occurs when the vertebrae above or below a fusion take on extra stress. The added stress can eventually degenerate the adjacent vertebrae and cause pain. • Nerve damage: Numbness or paralysis is possible from direct injury during the procedure. • Major vascular injury (rare): Internal and external jugular veins, vertebral, carotid and thyroid arteries • Dural tear, venous air embolism, and pneumothorax are rare but possible. • Vocal cord paresis, epiglottis paralysis, and aphasia require feeding tube placement.

PROGNOSIS

• Relief of arm pain: 92–100% (3) • Relief of neck pain: 73–83% • Weakness and numbness may persist for weeks to months.

REFERENCES

1. Daniels AH, Riew KD. Adverse events associated with anterior cervical spine surgery. J Am Acad Orthop Surg. 2008;16:729–738. 2. Padberg AM, Thuet ED. Intraoperative electrophysiologic monitoring: Consideration for complex spinal surgery. Neurosurg Clin N Am. 2006;17:205–226. 3. Bohlman HH, Emery SE. Robinson anterior cervical diskectomy and arthrodesis for cervical radiculopathy: A long-term follow-up of 122 pts. J Bone Joint Surg. 1993;75(9):1298– 1307. See Also (Topic, Algorithm, Electronic Media Element) • Somatosensory and motor evoked potentials • Electromyelogram

CLINICAL PEARLS

• Careful airway evaluation and management (video laryngoscopy, awake or asleep FOB may be considered) • Keep neutral position of the neck and minimize airway manipulation during intubation. • Neurophysiologic monitoring may be improved with TIVA. • Postoperative airway compromise can result secondary to hematoma formation, RLN injury, or soft-tissue swelling.

ANTERIOR MEDIASTINAL MASS Shital Vachhani, MD

BASICS DESCRIPTION

• Anterior mediastinal masses include teratomas, thyroid tumors, lymphomas, and thymomas. They can result in dangerous and fatal cardiovascular or pulmonary structure compression at the time of anesthesia induction, muscle relaxation, and positive pressure ventilation. • Patients present to the operating room for biopsy or excision of the mass via a sternotomy, thoracotomy, cervical mediastinoscopy, anterior parasternal mediastinoscopy, video-assisted thoracoscopic biopsy, or awake CT-guided percutaneous biopsy. • There are also case reports of patients with undiagnosed anterior mediastinal masses (AMM) presenting emergently to the operating room for ascending aortic aneurysm and Cesarean sections (1).

EPIDEMIOLOGY Prevalence

• Half of all mediastinal masses are anterior (2). • 60% of surgically resected lesions are neurogenic tumors, thymomas, and benign cysts (2).

Prevalence

In children, lymphoma is the most common AMM, followed by germ-cell tumors and thymic masses. Morbidity

• Masses in the anterior mediastinum are more likely to be malignant than those found in other mediastinal compartments. • Perioperative morbidity results from mass compression on vascular or pulmonary structures.

Mortality

Not available

ETIOLOGY/RISK FACTORS

• Depends on tissue diagnosis of mass, usually secondary to a mutation • Often an incidental finding

PHYSIOLOGY/PATHOPHYSIOLOGY

• During spontaneous ventilation (SV), airways are held open by baseline negative intrathoracic pressures and adherence of the pleura to the chest wall. • Intrathoracic versus extrathoracic masses: – Intrathoracic masses are found within the chest cavity. During SV, inspiration expands the

rib cage upward and outward and “lifts” the mass off vascular and respiratory structures. In the standing position, exhalation does not typically result in symptoms. However, in the recumbent and supine positions, exhalation can result in compression of structures. – Extrathoracic masses are located outside the chest cavity and are further divided into variable and fixed lesions. Variable lesions: Redundant airway tissue (snoring), tracheomalacia, etc. During SV, obstruction occurs during inspiration. The negative pressure that is generated in the chest, distal to the mass, results in collapse of the airway. During exhalation, the position pressure that is generated by the abdominal muscles, distal to the mass, stent the airway open. Fixed lesions: Goiter. Obstruction to airflow occurs during inspiration and exhalation. • AMMs (intrathoracic masses) can result in extrinsic compression of structures: – Respiratory: Trachea, major bronchus. The mass may prevent adequate ventilation by compressing the trachea/bronchus while perfusion remains unchanged. This can result in a V/Q mismatch called a pulmonary shunt. – Cardiovascular: Great vessels, right ventricular outflow tract (posterior mediastinal masses are more likely to affect the left atrium or ventricle). Encroachment does not produce hemodynamic effects, whereas compression results in clinical manifestations similar to pericardial tamponade. Right ventricular failure may be responsible for hypotension with resultant dead space lung physiology (blood flow to the alveoli is decreased; hypoxemia can result even in the absence of tracheal obstruction). • Infants and children have more compressible airways and may be more susceptible than adults to extrinsic airway obstruction (1). • Superior vena cava (SVC) syndrome: The thin-walled venous system is easily compressible by a large mediastinal mass. Thus, if there is obstruction to venous drainage from the upper body, this can cause interstitial edema. Therefore, collateral veins with low resistance become dilated.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Management depends on the anatomy and pathology of the mass, as well as the surgical procedure. • Look for compression of the heart, great vessels, and airway structures during induction and throughout the surgical procedure.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Respiratory symptoms: Nonproductive cough, stridor, wheezing, dyspnea, orthopnea that worsens with recumbency or lying flat • Syncope • Patient may be asymptomatic and the mass incidentally found on CXR.

History

Shortness of breath or cough when lying flat (1)

Signs/Physical Exam

• Use of accessory muscles • Plethora of the face (SVC syndrome)

TREATMENT HISTORY

If lymphoma, find out if pretreated with steroids or radiation to shrink the tumor. The disadvantage of pretreatment is that it might affect tissue pathology (diagnosis). MEDICATIONS

• Bronchodilators • Steroids, if part of a chemotherapeutic regimen

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Flow volume loops to look for extrinsic or intrinsic compression in the supine and upright positions (may see decrease in FEV1 and peak expiratory flow in supine position) (3). Their predictive value has been questioned, particularly with the advent of newer and sophisticated imaging modalities. • CXR often incidentally identifies the mass; further imaging should be ordered. • Arterial blood gas • CT/MRI of the chest to display the location and extent of airway or cardiovascular compromise; patients who are unable to lie flat may be done in the 30° angle, lateral, or prone position. • Echocardiogram to assess for cardiovascular effects (mass effect, cardiac compression, or pericardial effusion). Anterior masses tend to compress the right heart. • If thymoma, rule out myasthenia gravis by testing for acetylcholine receptor antibodies. • Fine needle aspiration for biopsy

CONCOMITANT ORGAN DYSFUNCTION

• Signs of SVC syndrome from compression • Dynamic cardiac or airway compression with positional changes • Parathyroid masses may be associated with hyperparathyroidism. • Thymomas may have concurrent myasthenia gravis or immune deficiency.

CIRCUMSTANCES TO DELAY/ CONDITIONS

• If the patient is a candidate to receive radiation or steroids to decrease the mass size • If there is a potential for severe airway compromise, but a cardiopulmonary bypass (CPB) machine and perfusionist are not available CLASSIFICATIONS

• Mediastinal masses are described based on their location relative to the heart: – Anterior: Teratomas, thyroid tumors, “terrible” lymphomas, thymomas (4Ts) – Middle: Lymph nodes, vascular masses – Posterior: Esophageal and neurogenic tumors, aneurysms

TREATMENT PREOPERATIVE PREPARATION Premedications

• If the patient is symptomatic, no benzodiazepines or opioids should be administered; they can compound respiratory effects. • If an awake, semi-sitting fiberoptic is planned (due to tracheal compression), glycopyrrolate can be administered as an antisialagogue, and lidocaine to topicalize the airway. Special Concerns for Informed Consent

• Thoracic epidural placement for tumor resection via a thoracotomy or sternotomy • Postoperative intubation and ventilation may be necessary. • CPB is a possibility.

INTRAOPERATIVE CARE Choice of Anesthesia

• Intubate while maintaining SV if possible • A rigid bronchoscope and surgeon should be available for immediate assistance if airway collapse occurs. The rigid bronchoscope can be inserted distal to the compression, and “stent” the area open allowing adequate oxygenation/ventilation. • Awake fiberoptic bronchoscopy may be appropriate if the mass appears to compress the trachea. The endotracheal tube acts similar to the rigid bronchoscope to “stent” the area open. Monitors

• In patients with SVC syndrome, intravenous access should be placed in the lower extremity. • Arterial line for blood pressure assessment and management; also if placed in the right radial position, can serve as an indicator of mediastinal compression of the innominate artery. Induction/Airway Management

• Femoral cannulation under local anesthesia with CPB readily available, if there is a potential for severe obstruction. If asymptomatic and there is no reason to believe that the mass will compress the respiratory or cardiovascular structures, slow controlled induction may be pursued. • If unsure, try to maintain SV with inhalational agents, ketamine, or dexmedetomidine and secure the airway. • A surgeon should be available in the room during induction in the event that the mass compresses the airway and SV is lost; or if a smaller endotracheal tube cannot be passed. A rigid bronchoscope can be passed distal to the site of compression and stent the airway open. Maintenance

• While SV is ideal for large masses, positive pressure ventilation with a volatile agent is

usually used to optimize surgical conditions. • Use of short-acting anesthetics is ideal. • Avoid muscle relaxants, if possible. If they are necessary for the procedure, assisted manual ventilation should be first attempted to assure that positive-pressure ventilation is possible (1). • Compression and cardiopulmonary collapse: – Mainstem the endotracheal tube or insert a rigid bronchoscope – Awaken the patient and return to SV – Lateral position or prone position; positional changes can displace the mass and alleviate compression. The history and physical is important to determine if the patient’s symptoms are alleviated with certain positional changes. – Chest compressions in the supine position – Sternotomy and surgical elevation of the mass off the great vessels – CPB

Extubation /Emergence

• Extubation should be performed only in a fully awake patient, with the rigid bronchoscope in the room for backup in the event of airway collapse. • Look for underlying tracheomalacia from tumor compression

FOLLOW-UP BED ACUITY

• Floor bed may be appropriate. • ICU care may be needed depending on the intraoperative course.

MEDICATIONS/LAB STUDIES/CONSULTS

• CBC to check for anemia • For thoracic epidurals, the acute pain service should be contacted.

COMPLICATIONS

• Damage to the surrounding structures from procedure (e.g., phrenic and recurrent laryngeal nerve) • Pneumothorax

REFERENCES

1. Slinger P, Karsli C. Management of the patient with a large anterior mediastinal mass: Recurring myths. Curr Opin Anaesthesiol. 2007;20(1):1–3. 2. Strollo DC, Rosado de Christenson ML, Jett JR. Primary mediastinal tumors. Part 1: Tumors of the anterior mediastinum. Chest. 1997;112(2):511–512. 3. Neuman GG, Weingarten AE, Abramowitz RM, et al. The anesthetic management of an anterior mediastinal mass. Anesthesiology. 1984;60:144–147. See Also (Topic, Algorithm, Electronic Media Element)

• Mediastinoscopy • Flow-volume loops • Superior vena cava syndrome • Recurrent laryngeal nerve

CODES ICD9

519.3 Other diseases of mediastinum, not elsewhere classified ICD10 J98.5 Diseases of mediastinum, not elsewhere classified

CLINICAL PEARLS

• History, physical, and review of imaging studies are critical in determining the extent of mediastinal mass involvement. • Major airway complications are more commonly seen in the postoperative period, rather than in the operating room.

ANTI-DIURETIC HORMONE (ADH) Daniel R.C. Nieva, MD

BASICS DESCRIPTION

Antidiuretic hormone (ADH), also known as vasopressin, regulates urinary volume and osmolality by decreasing diuresis; it also functions as a potent vasoconstrictor at higher doses. PHYSIOLOGY PRINCIPLES

• ADH is a nonapeptide (consists of nine amino acids) with an arginine vasopressin attached to the 8th amino acid location; thus also referred to as arginine vasopressin (AVP). • AVP (V1) serves as an important backup system for blood pressure control and

cardiovascular sympathetic modulation in the hypotensive and hypovolemic states. – Hypotension is sensed by baroreceptors in the left heart, aortic arch, and carotid sinus and is a very potent trigger for AVP release. It can increase levels by 10–1000-fold. – At these elevated concentrations, AVP acts as a vasoconstrictor of the mesentery, skin, and skeletal tissues by stimulating the V1 receptor on vascular smooth muscle.

• ADH (V2) increases tubular conservation of water and urine osmolality, while decreasing

plasma osmolality in response to decreased (5–10%) plasma volume, increased plasma osmolality, or pain, stress, hypoxia. – When extracellular fluid osmolality increases, osmoreceptors in the hypothalamus shrink, which stimulates ADH release from the posterior pituitary. – In the thick ascending loop of Henle, it increases solute (NaCl) reabsorption; however, water is impermeable, resulting in decreased osmolarity within the tubules. – In the collecting ducts, it acts on V2 receptors to increase water permeability and hence

water movement along the osmotic gradient (increases water reabsorption/conservation, no effect on solute). • V3 receptor agonist stimulates ACTH and cortisol secretion by activating corticotropinreleasing hormone. • Signaling cascades: – V1 and V3 activation stimulates phospholipase C, ultimately mobilizing intracellular calcium stored in the endoplasmic reticulum. – The V2 receptor responds to ADH through the activation of a G protein-coupled adenylyl

cyclase. ATP is converted to cAMP, which activates protein kinase. Protein kinase causes water channels to fuse with the apical cell membrane and increases its permeability to water. • AVP promotes platelet aggregation and coagulation by increasing endothelial release of factor VIII and von Willebrand factor (vWF).

ANATOMY

• Produced in the paraventricular and supraoptic nuclei of the hypothalamus and then transported by way of neuronal axons to the posterior pituitary, where it is stored in granules. – When extracellular fluid osmolality increases, these nuclei shrink and release ADH from the posterior pituitary. Conversely, a decrease in osmolality causes osmoreceptors to swell and suppress ADH release. • ADH is metabolized in the liver and kidneys and the half-life is between 5 and 20 minutes.

DISEASE/PATHOPHYSIOLOGY

• Diabetes insipidus (DI) is characterized by impairment in renal concentrating ability due to either decreased ADH secretion (central DI) or failure of the renal tubules to respond normally to circulating ADH (nephrogenic DI). – Central DI causes: Trauma and postsurgical state (neurosurgical), anatomic (tumors and infiltrative diseases, e.g., histiocytosis X), infectious (meningitis and encephalitis), hereditary, and vascular (pituitary apoplexy) – Nephrogenic DI causes: Chronic renal disease, electrolyte disorders (hypokalemia and hypercalcemia), sickle cell disease, hyperproteinemias, and drugs (most notably lithium). Nephrogenic DI is due to either a decreased response to circulating ADH or interference with the renal countercurrent mechanism. – Signs and symptoms of DI are polyuria and polydipsia. – Laboratory findings are increased plasma osmolarity and decreased urine osmolarity. – In the water deprivation test, water is withheld from the patient to induce dehydration and to assess urinary water retention. In DI, the plasma osmolarity increases without a urinary response to retain water. In central DI (hypothalamic), treatment with ADH concentrates the urine. In nephrogenic DI, the kidneys fail to produce hypertonic urine following the administration of exogenous ADH. – Treatment of central DI involves the administration of intranasal DDAVP (1-deamino-8-Darginine vasopressin). Nephrogenic DI therapy is directed toward the underlying disorder and ensuring adequate fluid intake. Thiazides induce diuresis causing an ablation of the medullary gradient, thus decreasing urine volume output. • Syndrome of inappropriate antidiuretic hormone (SIADH) is characterized by fluid retention, hypoosmolality, and hyponatremia due to excessive release of ADH. – Causes include CNS disorders including skull fracture; subdural or subarachnoid hemorrhage; acute encephalitis; TB meningitis; Guillain–Barré syndrome; malignant neoplasm; drugs including antineoplastics, oxytocin, narcotics, phenothiazines, tricyclic antidepressants, carbamazepine; positive pressure ventilation; and postoperative pain. – Signs and symptoms: Confusion, seizures, and coma due to osmotic water shifts causing brain edema – Laboratory findings include a decreased [Na+] (<130 mEq/L), decreased plasma osmolarity (<270 mOsm/kg), and hypertonic urine. – Treatment includes correction of the underlying cause, water restriction to 800–1,000 mL/d, demeclocycline which interferes with renal action of ADH, and 3% saline given over several hours. Central pontine myelinolysis may occur if serum Na+ is corrected too quickly.

PERIOPERATIVE RELEVANCE • Hyponatremia (plasma [Na+] <130 mEq/L) due to SIADH should be corrected prior to all elective procedures, even in the absence of symptoms. Lower concentrations may result in significant cerebral edema that can be manifested intraoperatively as a decrease in the MAC for volatile agents, or postoperatively as agitation, confusion, or somnolence. • Anesthetic agents have little direct effect on ADH secretion. Indirectly, the surgical stress response increases ADH secretion and may last 2–3 days postoperatively. • Vasopressin and synthetic agonists may be used to treat intraoperative hypotension, vasodilatory shock including anaphylaxis and sepsis, and during CPR. – Septic shock: Endogenous AVP depletion contributes to vasodilation. AVP, when combined with norepinephrine, increases peripheral vascular resistance and arterial blood pressure (1)[A]. Some markers of renal function are improved with short-term AVP infusion, and mortality is reduced at 28 days when AVP is combined with corticosteroids. Alone, AVP permits sparing of conventional vasopressors in septic patients with relative AVP deficiency (2)[B]. Therefore, AVP (0.01–0.04 U/min) is commonly used in the management of septic patients and is endorsed by international sepsis treatment guidelines (3)[A]. – Refractory hypotension in patients taking ACE inhibitors or ARBs. The administration of vasopressin 1–2 units may be helpful in refractory cases. – Cardiac arrest: 40 U of vasopressin via either the intravenous or intraosseous route can replace the first or second 1 mg dose of epinephrine in patients with pulseless arrest (pulseless electrical activity, ventricular fibrillation, or tachycardia) according to the 2010 American Heart Association guidelines on CPR (4)[B]. • DDAVP: In perioperative patients with mild hemophilia A and type 1 von Willebrand disease, desmopressin increases endothelial release of factor VIII and vWF. Orally administered ADH is essentially biologically inactive due to rapid hydrolysis by trypsin and therefore must be administered parenterally. DDAVP is the only clinically available ADH agonist and is bio-available via the intravenous, intranasal, and subcutaneous routes. EQUATIONS

The sodium deficit, or amount of NaCl necessary to raise plasma [Na+] to the desired level, can be estimated by the following formula:

[Na+] deficit = TBW × (desired [Na+] – measured [Na+]), where TBW = total body weight in kilograms

FIGURE 1. In the thick ascending loop of Henle, ADH increases NaCl reabsorption thereby decreasing osmolarity within the tubules. In the collecting ductules, ADH induces water reabsorption along the osmotic gradient resulting in more concentrated urine.

REFERENCES

1. Treschan TA, Peters J. The vasopressin system: Physiology and clinical strategies. Anesthesiology. 2006;105:599–612. 2. Patel BM, Chittock DR, Russell JA, et al. Beneficial effect of short-term vasopressin infusion during severe septic shock. Anesthesiology. 2002;96:576–582. 3. Holt NF, Haspel KL. Vasopressin: A review of therapeutic applications. J Cardiothorac Vasc Anesth. 2010;24:330–347. 4. Neumar RW, Otto CW, Link MS, et al. Part 8. Adult advanced cardiovascular life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122:S729–S767. See Also (Topic, Algorithm, Electronic Media Element)

• Diabetes insipidus • Carotid sinus • Syndrome of inappropriate diuretic hormone (SIADH) • Von Willebrand disease • Hyponatremia • Urine osmolarity

CLINICAL PEARLS

• Antidiuretic hormone (ADH) increases NaCl reabsorption in the loop of Henle and water permeability in the collecting duct resulting in increased water conservation, increased urine osmolality, and decreased plasma osmolality. • The management of nephrogenic DI is directed toward the underlying cause and also

includes fluids and thiazides. Central DI is treated with intranasal DDAVP. • Treatment of SIADH includes correction of the underlying cause, water restriction, demeclocycline and possibly 3% saline given over several hours. Central pontine myelinolysis may occur if serum Na+ is corrected too quickly. • Elevated AVP concentrations, triggered by hypotension, result in vasoconstriction. • Vasopressin and synthetic agonists may be used to treat intraoperative hypotension, anaphylactic and septic shock, and during CPR.

ANTIFIBRINOLYTICS Christopher Wray, MD

BASICS DESCRIPTION

• The 2 antifibrinolytic agents in current clinical use – epsilon-aminocaproic acid (EACA) and tranexamic acid (TA) – are synthetic lysine analogs that are similar in mechanism of action, molecular weight, metabolism, and clinical effects. • Clinical uses include prophylaxis and/or adjunctive therapy for the prevention of perioperative bleeding in a variety of patients and surgeries: – Cardiac surgery requiring cardiopulmonary bypass (CPB) – Liver transplantation or resection – Orthopedic procedures (e.g., revision joints, spinal surgery) PHYSIOLOGY PRINCIPLES

• Mechanism and regulation of fibrinolysis: The normal fibrinolytic response is a complex physiologic reaction that prevents excessive intravascular hemostasis at the site of a vascular injury. – Vascular injury results in the activation of pro-coagulant pathways that culminate in the formation of fibrin clot at the site of vascular injury. – Intravascular fibrin and thrombin initiate the normal fibrinolytic response. • Tissue plasminogen activator (tPA) and plasminogen are serine proteases in endothelial cells that are released at the site of vascular injury. They bind to positively charged lysine residues on the fibrin molecule. – tPA and plasminogen bind to fibrin which then converts plasminogen to plasmin. – Plasmin directly cleaves fibrin clot, resulting in fibrin degradation and clot breakdown. – Regulation of fibrinolysis occurs via multiple local and systemic mechanisms. A delicate balance between competing pro-coagulant and anti-coagulant systems occurs during normal intravascular homeostasis. • Mechanism of action of lysine analogs: – EACA and TA share a common mechanism of action by reversibly inhibiting the binding of plasminogen to charged lysine sites on the surface of fibrin molecules, thus preventing the conversion of plasminogen to plasmin. – Unlike the serine protease inhibitor aprotinin, lysine analogs do not directly inhibit the actions of plasmin. – The potency of TA is approximately 10 times higher than EACA. – Plasma half-life of both drugs is approximately 2 hours, and excretion is primarily via renal mechanisms. 95% of the drug is excreted unchanged in the urine. DISEASE/PATHOPHYSIOLOGY

• Excessive systemic fibrinolysis may be stimulated by:

– Disease states: Sepsis, massive trauma – Major surgery: Cardiac surgery with CPB, liver transplantation, and major orthopedic surgery • Consumptive coagulopathy is defined by the presence of the simultaneous generation of both thrombin and plasmin, which results in the potential for severe diffuse bleeding. • Systemic fibrinolysis may be detected clinically by the observation of excessive bleeding at sites of tissue injury: – Surgical wounds – Intravascular catheters – Invasive devices such as Foley catheters • Laboratory abnormalities reflecting the degradation of fibrin clot may assist in the diagnosis of fibrinolysis. They include: – Increased levels of fibrin split products – Increased D-dimer – Decreased levels of fibrinogen – Increased levels and activity of tPA – Characteristic abnormalities on thromboelastogram • Side effects of antifibrinolytics: – Renal: EACA has been shown to exhibit a range of nephrotoxicity (acute tubular necrosis, myoglobin-induced renal failure, glomerular capillary thrombosis) in patients following prolonged use and/or receiving high doses. Cardiac surgical patients with normal renal function who receive moderate dosing protocols do not demonstrate significant renal effects. Both drugs should be avoided in patients with severe renal dysfunction. – Central nervous system: Lysine analogs cross the blood–brain barrier and have the potential to cause neuronal hyperexcitability. TA has been associated with a higher level of seizure activity in cardiac surgical patients compared to aprotinin. – Immunologic: Lysine analogs have low molecular weights, making them less antigenic than larger molecules associated with anaphylaxis, such as aprotinin. – Prothrombosis: In non-heparinized surgical patients, co-administration of antifibrinolytics poses a potential concern for prothrombotic complications. Studies in cardiac and liver transplant surgery patients have not shown an increase in the rate of thrombotic complications in patients receiving antifibrinolytics (myocardial infarction, stroke, deep vein thrombosis, pulmonary embolism, or liver graft vascular thrombosis) (1,2).

PERIOPERATIVE RELEVANCE

• Antifibrinolytic therapy has been mainly used to control the consumptive coagulopathy that can occur during cardiac surgery with CPB, liver transplantation, and major orthopedic surgery.

• Cardiac surgery with CPB: Application of all extracorporeal circulation devices, including CPB, results in the continuous systemic generation of thrombin. Despite the use of heparin to prevent massive intravascular coagulation, thrombin generation continues throughout CPB. TPA release, stimulated by circulating thrombin, increases throughout the duration of CPP and remains elevated for many hours after (accompanied by accelerated fibrinolysis). Prophylactic antifibrinolytic therapy is regularly used to decrease CPB-associated fibrinolysis. – Multiple studies have demonstrated decreased postoperative transfusion, decreased risk of re-exploration, and reduced plasma markers of fibrinolysis compared to placebo. Additionally, no increase in acute coronary artery thrombosis has been shown to occur. TA has been studied more intensively than EACA in cardiac surgery (1,3,4). – TA may be administered in low- or high-dose regimens. Low-dose TA: 10 mg/kg loading dose, 1 mg/kg/hr infusion. High-dose TA: 50–150 mg/kg loading dose, 1 mg/kg/hr infusion. – EACA dosages: 5–10 g loading dose prior to incision, 1 g/hr infusion. The maximum safe total dosages of EACA have been described between 30 and 90 g. – Abnormal renal function requires lower doses. – Some experts recommend the continuation of antifibrinolytic therapy for up to 12 hours following CPB, although common practice is to discontinue treatment upon completion of surgery (5). – Topical TA administered in the wound at surgical closure has been shown to reduce postoperative blood drainage (5). • Orthotopic liver transplantation (OLT): Enhanced fibrinolysis is common with OLT, especially during the anhepatic and early post-anhepatic phases of the procedure. Increased tPA activity and decreased fibrinolytic inhibitor activity regularly occur during OLT. Fibrinolysis contributes to blood loss and transfusion requirements during OLT. Serial laboratory coagulation testing (thromboelastography, fibrinogen, D-dimer, fibrin degradation products) is routinely employed to assist in the diagnosis of excessive fibrinolysis during OLT. – Clinical use of antifibrinolytics in OLT varies by practice: Prophylactic infusion and selective bolus rescue dosing have been described. – Both TA and EACA have been used clinically in OLT for many years, although TA has been studied more extensively (2). – TA has not been shown to increase the incidence of postoperative deep vein thrombosis or pulmonary embolism (3,6). – EACA: A single 1 g dose has been shown to be effective in normalizing fibrinolytic abnormalities on thromboelastography. However, it has not definitively been shown to impact transfusion requirements during OLT (2). – TA has been shown to decrease blood loss and reduce transfusion requirements in prospective studies during OLT (2,3). – Significant preoperative renal dysfunction poses an increased risk for the exacerbation of acute kidney injury by antifibrinolytics. – Thromboembolic complications are a rare but devastating intraoperative complication during OLT; there are concerns regarding the pro-thrombotic potential of antifibrinolytics

in this setting. However, antifibrinolytic therapy has never been determined as a definitive cause of thromboembolic complications in this patient population. Antifibrinolytic therapy should be withheld in OLT patients with a known pre-existing hypercoagulable state (2). • Orthopedic surgery: Antifibrinolytic therapy has been employed in a variety of major orthopedic procedures with a risk of significant blood loss, including adult and pediatric scoliosis spine surgery and revision joints. Major prolonged orthopedic surgery may result in significant bone and tissue trauma that can stimulate fibrinolysis. The use of a lower extremity tourniquet, as in total knee arthroplasty, may be associated with enhanced fibrinolysis. – Total knee arthroplasty: Studies have demonstrated that TA use decreases blood loss and transfusion requirements (3,6). – Pediatric scoliosis: TA has also been shown to decrease intraoperative blood loss. – A variety of regimens, including preoperative and postoperative oral and IV dosing, have been described. • Future directions in antifibrinolytic therapy: – Fibrinogen levels: Effective antifibrinolytic therapy requires maintenance of adequate levels of fibrinogen. Low fibrinogen levels are associated with significant post-CPB bleeding in cardiac surgery. Cryoprecipitate transfusion has been the standard treatment for increasing fibrinogen levels. Newly developed factor concentrates, including virusinactivated purified fibrinogen, may be an alternative to cryoprecipitate and fresh frozen plasma for the treatment of hypofibrinogenemia (7). – Aprotinin: Following the withdrawal of aprotinin in 2007, antifibrinolytic therapy has been limited to the use of the lysine analogs. – CU-2010—a synthetic protease inhibitor with properties similar to aprotinin—has recently been described as a new antifibrinolytic agent; however, further clinical studies are required (8).

REFERENCES

1. evi M. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: A meta-analysis of clinically relevant endpoints. Lancet. 1999;354:1940–1947. 2. Xia VW, Steadman RH. Antifibrinolytics in orthotopic liver transplantation: Current status and controversies. Liver Transplant. 2005;11(1):10–18. 3. Levi M. Pharmacologic methods to reduce perioperative bleeding. Transfusion. 2008;48:S31–S38. Laupacis A. Drugs to minimize perioperative blood loss in cardiac surgery: Meta-analysis using perioperative blood transfusion as the outcome. The International Study of Peri-operative Transfusion (ISPOT) Investigators. Anesth Analg. 1997;85:1258–1267. 4. Edmunds HL. Managing fibrinolysis without aprotinin. Ann Thorac Surg. 2010;89:324–331. 5. Eubanks JD. Antifibrinolytics in Major Orthopaedic Surgery. J Am Acad Orthop Surg March 2010;18: 132–138. 6. evy JH. Prohemostatic Treatment in Cardiac Surgery. Seminars in Thrombosis and Hemostasis 2012;38:237–243.

7. ietrich W. Anesthesiology. 2009;110(1):123–130.

ADDITIONAL READING

• Dalmau A. Hemostasis and coagulation monitoring and management during liver transplantation. Curr Opin Organ Transplant. 2009;14;286–290. • Ide M. Lessons from the aprotinin saga: Current perspective on antifibrinolytic therapy in cardiac surgery. J Anesth. 2010;24:96–106.

See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary embolism • Cardiopulmonary bypass • D-dimer • Fibrinogen

CLINICAL PEARLS

• Excessive intravascular activity of the fibrinolytic system that results in clinically significant bleeding may be stimulated by disease states or major surgery. • Following the withdrawal of aprotinin, current antifibrinolytic therapy is limited to the lysine analogs—EACA and TA. • TA has been better studied than EACA for perioperative antifibrinolytic therapy. • TA has been shown to improve perioperative bleeding in cardiac surgery with CPB, OLT, and major orthopedic surgery.

ANTITHROMBIN III Fei Zheng, MD, MPH, MS Nanhi Mitter, MD

BASICS DESCRIPTION

• Antithrombin III (ATIII) is one of the most important coagulation inhibitors; it stops the progression of clot formation by inhibiting serine proteases. It is also known as antithrombin or heparin cofactor 1. • ATIII is the fundamental enzyme for the therapeutic action of heparin.

PHYSIOLOGY PRINCIPLES

• ATIII is a single-chain glycoprotein weighing 58 kD. It is produced by the liver and vascular endothelial cells and is composed of 432 amino acids. ATIII circulates in the plasma with a half-life of 2–3 days. • ATIII inhibits serine proteases (IXa, XIa, XIIa and plasmin to a lesser degree); by blocking their action, it prevents thrombin and factor Xa activity and ultimately clot formation. • There are 2 functional sites on antithrombin: – Site that binds serine proteases – Site that binds glycosaminoglycans (i.e., heparin) • ATIII concentrates have been developed. Currently, there are 2 types available for intravenous administration: – Human plasma-derived concentrate (i.e., Thrombate III®). Prior to usage, it needs to be reconstituted with sterile water and used within 3 hours. Must be administered intravenously; other medications should not be given through the same line. Classified as a pregnancy category B; safety has not been established in the pediatric population. Possible adverse reactions: Dizziness, chest tightness, nausea, unpleasant taste in the mouth, chills, or cramps. Additionally, because it is derived from plasma, it has the potential for infectious agent transmission (i.e., Creutzfeldt–Jakob, hepatitis). – Recombinant human concentrate (i.e., ATryn®) is produced in transgenic goats with a copy of the human antithrombin gene. Prior to usage, it needs to be reconstituted with sterile water and should be used within 3 hours. It is available for intravenous use only. Classified as a pregnancy category C; safety has not been established in the pediatric population. Contraindications to use include a hypersensitivity to goat or goat milk. The most common adverse reactions include hemorrhage and infusion site reaction. ANATOMY

Produced by the liver and vascular endothelial cells DISEASE/PATHOPHYSIOLOGY

• ATIII can have decreased levels or impaired function from either acquired or familial causes. • Acquired causes: – Impaired function Heparinized patients; can decrease to 1/3rd normal values Estrogen-based contraceptives – Decreased levels Neonates/infants <6 months old possibly secondary to severe malnutrition Pregnancy: Third trimester, preeclampsia, eclampsia, disseminated intravascular coagulation (DIC) Cirrhosis, nephrotic syndrome, estrogen, chemotherapy, malnutrition, inflammatory bowel disease, small bowel resection, etc. • Familial antithrombin deficiency is mostly an autosomal dominant trait and has a 1:2,000– 5,000 prevalence in the general population. Up to 5% of individuals can present with thrombotic disease. – Type I (quantitative): Various DNA mutations that reduce the quantity of antithrombin. Diagnosed with immunoassays. – Type II (qualitative): 1 amino acid change that reduces the quality of antithrombin at either the heparin or the thrombin binding site. Diagnosed with functional assays. – Type III: Insufficient heparin receptors (normal quantity and quality of antithrombin) – Clinical presentations: Recurrent thromboembolic events Peak incidence between 15 and 40 years of age Most common site of thrombosis is the legs. Thrombosis or fetal loss during pregnancy Resistance to heparin Family history

PERIOPERATIVE RELEVANCE

• Management of patients with ATIII deficiency (qualitative or quantitative) is controversial. Some potential treatment options that are currently available include: – Asymptomatic patients: No prophylaxis is needed but patients should be informed of the increased risk of thromboembolic events under prothrombotic conditions (i.e., prolonged bed rest, major surgeries or trauma, pregnancy, carcinoma, oral contraceptives). – Heparin is generally the first-line treatment but it may deplete the low concentration of normal antithrombin already present. Heparin binds to and causes a conformational change that results in a 4,000-fold increase in ATIII activity. – Coumadin may be added as an oral maintenance after initiation of heparin. – Fresh frozen plasma transfusion can provide a source of antithrombin. Drawbacks include transfusion-related acute lung injury (TRALI) and the transmission of infections. – Antithrombin concentrates may be considered for: Thromboembolic prophylaxis or treatment of ATIII deficiency, predominately for surgical and peripartum women

Homozygous antithrombin deficiency not responding to heparin. Shown to be as effective as 2 units of FFP in heparin-resistant patients undergoing elective cardiac surgery Acute situations (i.e., ongoing thrombosis, DIC) Critically ill individuals Patients in whom anticoagulation is contraindicated – Steroids may stimulate antithrombin synthesis; however, more research is needed.

EQUATIONS

• Human plasma-derived concentrate: – Initial dose = [(desired – current antithrombin level expressed in% of normal level) × weight in kg] /1.4 – For example: 70 kg patient with baseline antithrombin level of 50% and desired level of 150%. Initial dose = [(150 – 50) × 70] / 1.4 = 5,000 IU – Maintenance dose: 60% of initial dose, given once every 24 hours • Recombinant human concentrate: – Initial dose = [(100 – current antithrombin activity expressed in% of normal level) × weight in kg] / 2.3 (1.3 in parturients) – For example: 70 kg patient with a baseline antithrombin level of 50%. Initial dose = [(100 – 50) × 70] / 2.3 = 1,522 IU – Maintenance dose = [(100 – current antithrombin activity expressed in% of normal level) × weight in kg] / 10.2 (5.4 in parturients)

REFERENCES

1. Ambruso D, Jacobson LJ, Hathaway WE. Inherited antithrombin III deficiency and cerebral thrombosis in a child. Pediatrics. 1980;65: 125–131. 2. Avidan MS. Recombinant human antithrombin III restores heparin responsiveness and decreases activation of coagulation in heparin-resistant patients during cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2005;130(1):107–113.

3. Beresford CH. Antithrombin III deficiency. Blood Rev. 1988;2:239–250. 4. http://en.wikipedia.org/wiki/Alexander_Schmidt_%28physiologist%29 5. http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProd 6. http://www.talecris-pi.info/inserts/thrombate.pdf 7. Patnaik MM. Inherited antithrombin deficiency: A review. Haemophilia. 2008;14:1229– 1239. 8. Perry DJ. Antithrombin and its inherited deficiencies. Blood Rev. 1994;8:37–55. 9. Sawamura A, Gando S, Hayakawa M. Effects of antithrombin III in patients with disseminated intravascular coagulation diagnosed by newly developed diagnostic criteria for critical illness. Clin Appl Thromb Hemost. 2009;15(5):561–566. 10. The Medical Letter Online. Recombinant human antithrombin (ATryn). Med Lett Drug Therap. 2009;51(1323):83–84.

See Also (Topic, Algorithm, Electronic Media Element) • End-stage liver disease • Cardiopulmonary bypass • Fresh frozen plasma

CLINICAL PEARLS

• If ACT levels remain unchanged following heparin administration: – Flush the line through which heparin was given – Verify that the heparin is entering the bloodstream (e.g., the intravenous line is within a vessel) – Verify that the correct heparin dose was administered – Check the expiration date on the heparin vial – Administer additional heparin (up to 600 U/kg) – Consider administering ATIII concentrate – Consider administering FFP (2–4 units in adults)

AORTIC DISSECTION Michael L. Boisen, MD David G. Metro, MD

BASICS DESCRIPTION

• Aortic dissection is characterized by the development of a tear in the aortic intima that allows blood to enter a false lumen and cause a separation in the layers of the vessel wall. • It is the most common aortic catastrophe, occurring with a frequency exceeding that of abdominal aortic aneurysm rupture. • Most acute dissections (80%) develop in the absence of a pre-existing aneurysm; thus, distinction should be made between the terms “dissection” and “aneurysm.” • The diagnosis of aortic dissection is missed in up to 40% of patients at initial presentation as physical findings may be absent or nonspecific or mimic conditions for which the therapeutic strategy is dissimilar (e.g., myocardial ischemia). EPIDEMIOLOGY Incidence

• Peak incidence in the 6th and 7th decades with the mean age of diagnosis at 63 years • Males account for 65% of cases • Circadian and seasonal patterns have been described with peak frequency between 8:00 AM and 9:00 AM and during winter months. • 3.5 per 100,000 persons per year (US data)

Prevalence

Actual prevalence unknown since many patients (∼20%) die prior to hospital presentation. Autopsy series report 1 acute aortic dissection for every 128 to 745 autopsies. Morbidity

Neurologic complications are the main cause of disability among survivors. Mortality

• Acute dissection of the ascending aorta has a 30-day mortality rate of 20% with surgical repair and 50% with medical therapy alone. • Death most often results from aortic rupture, cardiac tamponade, stroke, and visceral ischemia. ETIOLOGY/RISK FACTORS

• Hypertension (72%) • Atherosclerosis (31%) • Smoking

• Bicuspid aortic valve • Coarctation • Deceleration trauma • Cocaine/crack • Pregnancy • Iatrogenic (percutaneous cardiac and aortic or valvular surgical procedures) • Hereditary fibrillinopathies (Marfan, Ehlers–Danlos, annuloaortic ectasia, and familial aortic dissection) • Vascular inflammation (Behet’s disease, syphilitic aortitis, Takayasu arteritis, and giant cell arteritis)

PATHOPHYSIOLOGY

• The development of a tear in the intimal layer of the aorta exposes the medial layer to the force of intraluminal blood flow. Entry of blood cleaves the intima and media longitudinally in an anterograde and/or retrograde direction; this serves to create a second or “false” lumen, separated from the true lumen by an intimal flap. • Propagation of aortic dissection is linked to mean, peak, and diastolic recoil arterial pressure as well as the rate of rise of aortic pressure (aortic dP/dt). • Malperfusion of branch vessels can occur due to occlusion by the intimal flap or by compression of the true lumen by expansion of the false lumen. • Most originate in the ascending aorta (65%), followed by the descending aorta (20%), aortic arch (10%), and abdominal aorta (5%).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Hemodynamic stabilization, pain control, and blood pressure optimization are priorities of initial management. In general, systolic blood pressure should be maintained at 100–120 mm Hg or the lowest level that maintains effective end-organ perfusion. • In the past, uncomplicated distal aortic dissection (Stanford B, DeBakey III) was managed medically; however, endovascular techniques are increasingly being applied. • Uncomplicated distal aortic dissection (Stanford B, DeBakey III) was historically managed medically; however, endovascular techniques are increasingly being applied.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Sudden, severe chest, back, and abdominal pain are the most common symptoms (>90%). • Syncope (up to 20%) with or without a history of pain • Neurologic symptoms (stroke, spinal cord ischemia, peripheral nerve ischemia) • Acute heart failure (7%) due to myocardial ischemia or acute aortic insufficiency • Limb ischemia • Hoarseness (due to recurrent laryngeal nerve compression)

History

• 96% of acute aortic dissections are identified with the following prediction model: – Aortic pain with immediate onset, a tearing or ripping character, or both

– Mediastinal widening, aortic widening, or both on chest radiography – Pulse differentials (absence of a proximal extremity or carotid pulse), blood pressure differentials (systolic pressure difference >20 mm Hg between arms), or both

Signs/Physical Exam

• Hypertension (69% of distal and 36% of proximal dissections) • Hypotension, shock, or tamponade (27% of proximal dissections) • Pulse or blood pressure differentials (20%) • Focal neurologic deficits (12%) • Murmur of aortic insufficiency (32%) • Pleural effusion (left > right) • Horner syndrome • Superior vena cava syndrome

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Baseline and serial cardiac biomarkers, BUN/Cr, CBC with platelets, coagulation profile and TEG, if available • ECG may be normal (∼30%) or show nonspecific ST-T changes (40%), left ventricular hypertrophy (26%), ischemia (15%), or infarction (10%). • Chest radiograph findings include mediastinal widening (61%), abnormal aortic contour (49%), pleural effusion (19%), displacement/calcification of aorta (14%). Normal findings are present in 12% of patients. • CT angiography is quick, highly sensitive, and specific; 64-slice multidetector CT with cardiac gating may allow for simultaneous evaluation of pulmonary and coronary arteries. • TEE is highly sensitive for ascending aortic dissection and allows rapid evaluation of hemodynamic instability (tamponade, coronary dissection, valvular regurgitation, tension hemothorax, etc.). • MRI/MRA has high sensitivity and specificity, avoids radiation, and iodinated contrast; but is more time-consuming and contraindicated with metallic implants. • Aortography: Previously the reference standard, this is performed less often and rarely as the initial study.

CONCOMITANT ORGAN DYSFUNCTION

• Compromise of aortic branches and subsequent malperfusion can affect several systems: – Cardiovascular: Acute aortic valvular insufficiency due to aortic root dilation or leaflet disruption; ischemia/infarction (dissections often arise from right sinus of Valsalva causing inferior wall myocardial infarction); limb ischemia from subclavian or iliac arteries – Neurologic: Syncope, stroke (innominate or common carotid arteries), spinal cord ischemia (radicular arteries), peripheral ischemic neuropathy – Pulmonary: Left pleural effusion/hemothorax – Renal: Ischemia, infarction, acute renal failure • Gastrointestinal: Abdominal organ ischemia (celiac, mesenteric arteries)

CIRCUMSTANCES TO DELAY/CONDITIONS

• Delays are associated with increased mortality; thus, evaluation should be limited to the acquisition of appropriate diagnostic studies and evaluation of conditions that will alter surgical candidacy or affect perioperative management. • Pericardiocentesis as a temporizing measure for tamponade has been associated with increased risk of PEA arrest and death compared to immediate sternotomy and surgical control of the aorta.

CLASSIFICATIONS

• Acute (<2 weeks) or chronic (>2 weeks) • Stanford: – Type A: Ascending aorta involved – Type B: Ascending aorta not involved (distal to takeoff of left subclavian artery) • DeBakey: – Type I: Ascending aorta, arch, descending aorta – Type II: Ascending aorta only – Type IIIa: Descending aorta only – Type IIIb: Descending and abdominal aorta

TREATMENT PREOPERATIVE PREPARATION Premedications

• Short-acting drugs permit rapid termination of effect, if desired, and should be considered. • Morphine, beta-blockers, and vasodilating drugs can be used to control pain and blood pressure. Esmolol is ultra-short-acting and has organ-independent elimination (metabolized within red blood cells). • Sodium nitroprusside may cause an increase in aortic dP/dt; it is generally added only after a negative inotrope is administered. • Nicardipine may be preferred in patients intolerant of beta-antagonists and does not cause a reflex tachycardia. • Enalaprilat may be useful in refractory hypertension due to renal artery compromise. • Phenylephrine and norepinephrine are preferred pressors due to a relative lack of associated increase in aortic dP/dt. INTRAOPERATIVE CARE Choice of Anesthesia

• No superiority has been demonstrated with any given anesthetic technique. • For open repair, GETA is typically employed, alone or in combination with epidural anesthesia; epidural placement may be precluded by hemodynamic instability. • Evoked-potentials monitoring may influence technique (i.e., volatile anesthetic concentration, use of muscle relaxant). • For endovascular repair, local, regional, and general techniques may be used.

Monitors

• ECG with ST-segment analysis • Temperature (central and peripheral sites if bypass is to be used) • Foley catheter • Arterial line: Right radial artery may be preferred if blood flow to the left subclavian artery is disrupted due to dissection or cross-clamp placement. Femoral artery insertion may permit monitoring of distal perfusion pressures. • Central venous access may be appropriate for IV access and administration of vasoactive medications. • Pulmonary artery catheterization can provide SvO2, SVR, CO, PAP.

• TEE aids in diagnosis, anatomic localization, identification of complications, and characterization of valvular and ventricular function in real time. • Lumbar drains and evoked-potentials may be placed for patients at risk for spinal cord ischemia. • The potential for catastrophic hemorrhage necessitates appropriate vascular access, availability of blood products, rapid infuser system, and autologous red cell salvage. Induction/Airway Management

• Slow, controlled titration of medications to the desired effect can help maintain hemodynamic stability. Hypertension and tachycardia increase shear stress and risk of rupture. • Single-lumen ETT may be typically placed for a median sternotomy approach. • Lung isolation with a double lumen tube or bronchial blocker aids in the exposure of the descending aorta and is preferred for procedures using the lateral thoracotomy approach. Maintenance

• Thermoregulation: Forced air and fluid warming systems are necessary due to significant heat loss with open procedures. • Fluid management: Maintenance of intravascular volume may be challenging due to significant hemorrhage and evaporative losses; no specific colloid or crystalloid strategy has emerged as superior. • Coagulation: Consumption and dilution of coagulation factors and platelets may be significant; replacement is guided by conventional coagulation studies as well as TEG, if available. • Renal protection: Maintenance of renal blood flow and urine output is essential; IV mannitol and fenoldopam can be employed to reduce the risk of kidney injury. Extubation/Emergence

• Ongoing cardiac or pulmonary instability, bleeding, hypothermia, or neurologic injury may necessitate continued mechanical ventilation; otherwise patients may be extubated at the conclusion of the procedure. • Pain, hypertension, and tachycardia should be anticipated and addressed.

POSTOPERATIVE CARE

BED ACUITY

Intensive care unit COMPLICATIONS

• Aortic rupture • Cardiac failure (ischemia, aortic insufficiency, tamponade) • Postoperative pulmonary failure • Neurologic deficits (stroke, paraplegia) • Renal insufficiency

REFERENCES

1. Clouse WD, Hallett Jr JW, Schaff HV, et al. Acute aortic dissection: Population-based incidence compared with degenerative aortic aneurysm rupture. Mayo Clin Proc. 2004;79:176–180. 2. Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): New insights into an old disease. JAMA. 2000;283:897–903. 3. Golledge J, Eagle KA. Acute aortic dissection. Lancet. 2008;372:55–66. 4. Penco M, Paparoni S, Dagianti A, et al. Usefulness of transesophageal echocardiography in the assessment of aortic dissection. Am J Cardiol. 2000;86:53G–56G. 5. von Kodolitsch Y, Schwartz AG, Nienaber CA. Clinical prediction of acute aortic dissection. Arch Intern Med. 2000;160:2977–2982. 6. Isselbacher EM, Cigarroa JE, Eagle KA. Cardiac tamponade complicating proximal aortic dissection: Is pericardiocentesis harmful? Circulation. 1994;90:2375–2379.

ADDITIONAL READING

• Nienaber CA, Eagle KA. Aortic dissection: New frontiers in diagnosis and management. Part I: From etiology to diagnostic strategies. Circulation. 2003;108:628–635. • Nienaber CA, Eagle KA. Aortic dissection: New frontiers in diagnosis and management. Part II: Therapeutic management and follow-up. Circulation. 2003;108:772–778.

See Also (Topic, Algorithm, Electronic Media Element) • Intubation/extubation criteria • Aortic rupture

CODES ICD9 • 441.00 Dissection of aorta, unspecified site • 441.01 Dissection of aorta, thoracic • 441.02 Dissection of aorta, abdominal ICD10

• I71.00 Dissection of unspecified site of aorta • I71.01 Dissection of thoracic aorta • I71.02 Dissection of abdominal aorta

CLINICAL PEARLS

• Acute dissection of the proximal aorta is a surgical emergency, and preoperative evaluation should be expedited. • Preoperative management is directed at the reduction of arterial pressure and aortic dP/dt. • Monitoring is essential to anesthetic management and should be individualized to the specifics of the patient, nature of dissection, and surgical procedure.

AORTIC PRESSURE CURVE Ryan Crowley, MD

BASICS DESCRIPTION

• The aortic pressure curve is measured directly with an indwelling needle or catheter that is inserted while the chest is open. The pressure in the aorta can also be directly measured by percutaneous catheters advanced centrally from peripheral arteries. • A transducer is then attached to the catheter to provide an arterial pressure tracing on a physiologic monitor. • Commonly, a more accessible central artery (femoral) or peripheral artery (radial) is accessed using various techniques to place a catheter into the artery. PHYSIOLOGY PRINCIPLES

• Direct monitoring of the arterial pressure curve allows for beat-to-beat measurement of blood pressure. • Simultaneously measuring both the left ventricular and aortic pressures demonstrates that pressure rapidly rises in the left ventricle (LV) during early systole (see Figure 1). • Isovolumetric contraction is the period between mitral valve closure and aortic valve opening. When the pressure in the LV exceeds the aortic diastolic pressure, the aortic valve opens and the upslope of the aortic pressure tracing begins. • The peak of the aortic pressure tracing is the systolic blood pressure and in the absence of significant aortic valve disease, also represents the LV end-systolic pressure. • As the ventricle stops contracting and begins to relax, the pressure falls in the aorta and the LV. When the pressure in the aortic root exceeds the LV pressure, the aortic valve closes. This represents the second heart sound (S2). • The dicrotic notch on the downslope of the aortic pressure tracing represents the closure of the aortic valve. The sudden closure of the valve briefly increases the pressure in the aortic root. • The pressure continues to fall after the dicrotic notch as blood “runs off” to the peripheral circulation. The lowest pressure prior to the next ejection is the diastolic blood pressure. • Mean arterial pressure (MAP) can be estimated by the calculation: MAP = (2DBP + SBP)/3; where DBP is diastolic blood pressure and SBP is systolic blood pressure. ANATOMY

• The aorta is an artery composed of 3 layers. From the lumen outward it is composed of the intima, the media, and the adventitia. • All arteries share a similar anatomical structure, but as arteries course to more peripheral locations, the compliant media decreases in thickness. Consequently, peripheral arteries are less compliant than central arteries. As measurements are made in progressively more distal arteries, there is an increase in pulse pressure (increased systolic and decreased diastolic

pressure) with only a very slight decrease in MAP. • Due to transmission of the pressure wave from a central to peripheral location, the onset of the pressure curve is slightly delayed in peripheral locations as compared to the aorta.

DISEASE/PATHOPHYSIOLOGY

• The aortic pressure curve can be suggestive of several pathologic states. • A slow upstroke of the pressure tracing (decreased dP/dT) can be observed with: – Poor LV contractility – Aortic stenosis or arterial stenosis (e.g., coarctation of the aorta) if measured distal to the obstruction – Overdampening, however, can also present in this manner and should be ruled out. • An extra wave may be seen in the aortic pressure curve, known as an anacrotic notch, which occurs prior to peak systolic pressure. This phenomenon is most often observed in aortic valve disease and is representative of high velocity flow. • “Run off" describes the slope of the aortic pressure curve after the dicrotic notch and corresponds to the afterload that the heart must contract against. – Slow “run off" may be seen in high systemic vascular resistance (SVR) states such as vasoconstrictor administration or a distal obstruction such as aortic coarctation – Rapid “run off" may be seen with poor arterial compliance, aortic insufficiency, or a low SVR state (e.g., sepsis, anaphylaxis) • A wide pulse pressure can be indicative of very low arterial compliance (e.g., atherosclerotic disease) or aortic insufficiency (good LV function with significant diastolic run-off due to an incompetent aortic valve). • Significant fluctuations in the aortic and arterial pressure tracings with respiration (>15%) indicate decreased ventricular filling and may resolve with volume administration. • The area under the curve (AUC) of the aortic pressure curve is proportional to stroke volume. • Given the same pressure, narrow curves with a small AUC represent smaller stroke volumes than wide or “full” pressure tracings. This principle is the basis for various cardiac output measurement devices that analyze the arterial waveform to estimate cardiac output. • In aortic stenosis, the LV pressure tracing peak is significantly higher than the aortic pressure peak. – The area between the 2 tracings is the mean gradient. – The difference between the 2 systolic peaks is the peak-to-peak gradient. The peak-to-peak gradient is lower than the peak instantaneous gradient (PIG) derived from echocardiography.

PERIOPERATIVE RELEVANCE

• Direct arterial blood pressure monitoring (typically peripherally) is indicated whenever significant or rapid changes in blood pressure are anticipated. • When displayed on a monitor with a static scale, the clinician can detect changes in systemic blood pressure immediately by observing changes in the arterial pressure tracing. • The blood pressure value displayed on physiologic monitors is averaged over many preceding seconds while changes in the waveform are displayed without any delay. • Continuous MAP determination can be utilized to ensure appropriate end-organ perfusion

pressures to the brain, kidneys, etc. in patients with limited reserve. • Continuous diastolic blood pressure measurements can be used to ensure adequate LV perfusion in patients at risk for ischemia (especially in conjunction with monitoring of pulmonary capillary wedge pressure [PCWP], left atrial pressure [LAP], or pulmonary artery diastolic pressure [PADP]). • Continuous systolic blood pressure measurement can be used to minimize aortic wall tension in patients with significant aortic disease (e.g., aneurysm or dissection).

EQUATIONS

• MAP = 2/3 DBP + 1/3 SBP; where MAP is mean arterial pressure, DBP is diastolic blood pressure, and SBP is systolic blood pressure • MAP = (2 [DBP + SBP])/3 • CO = (MAP – CVP) × SVR; where CO is cardiac output, MAP is mean arterial pressure, CVP is central venous pressure, and SVR is systemic vascular resistance

GRAPHS/FIGURES

FIGURE 1. Aortic pressure curve (solid line) with the left ventricular pressure curve (dashed lines) superimposed.

REFERENCES

1. Marik PE, Cavallazzi R, Vasu T, et al. Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: A systematic review of the literature. Crit Care Med. 2009;37(9):2642–2647.

2. Morgan P, Al-Subaie N, Rhodes A. Minimally invasive cardiac output monitoring. Curr Opin Crit Care. 2008;14(3):322–326. See Also (Topic, Algorithm, Electronic Media Element) • Cardiac output • Aortic stenosis

CLINICAL PEARLS

• Blood is ejected from the left ventricle to the aorta during the period where the upstroke of the aortic pressure curve meets the left ventricular pressure curve and until the dicrotic notch. • Respiratory variation in the aortic pressure tracing predicts for volume responsiveness. • Direct measurement of arterial pressure allows for the continuous determination of perfusion pressures to end-organs. • As one measures arterial pressure from proximal to distal locations, the – Systolic pressure increases – Diastolic pressure decreases – Pulse pressure increases – MAP slightly decreases

AORTIC REGURGITATION Brian L. Marasigan, MD

BASICS DESCRIPTION

• The aortic valve, normally consisting of 3 leaflets, opens during ventricular systole and closes during diastole. Valve closure prevents backflow of blood from the aorta to the left ventricle (LV) and helps maintain aortic diastolic pressure and coronary perfusion pressure. • Aortic regurgitation (AR) is the presence of a backflow leak through the valvular apparatus during diastole. – Ranges in severity from trace, mild, moderate, or severe; it is classified by the amount of regurgitant volume, regurgitant orifice area size, and pressure equalization half-time by echocardiography. – Regurgitation may be associated with any condition that alters aortic valve closure. Aortic dilation, aneurysm, dissection, and abscess are external causes of aortic valve dysfunction and account for about half of all AR cases. Rheumatic valve disease, collagen vascular diseases, connective tissue diseases (especially Marfan syndrome (1)[C]), congenital malformations, senile degeneration, and infective endocarditis are direct valvular conditions that commonly produce AR in the remainder of cases. – Acute AR is the sudden onset of backflow leak usually due to an acute event such as aortic dissection or valvular trauma. – Chronic AR has a gradual onset and may be sustained for many years. – May also accompany aortic stenosis—a narrowing of the open valvular area

EPIDEMIOLOGY Prevalence

• Worldwide, rheumatic heart disease is the most common cause of AR. • In the US, congenital and degenerative valvular and aortic disease is most common. • Congenital bicuspid aortic valves occur in 1–2% of the US population and may contribute to AR.

Prevalence

• 13% in men, 8.5% in women in a Framingham study (2) • In the US population, severe AR is <1% (3). • Chronic AR is more prevalent than acute AR.

Morbidity

• Acute AR has a higher rate of morbidity and mortality due to the underlying pathophysiology. This can result in diastolic and systolic dysfunction and eventually decompensation (CHF). • Chronic AR mortality is related to the eventual decompensation of the LV; it is more

common in severe AR. Decreased ejection fraction and LV function have a poor prognosis for recovery, even after repair. • Surgical management becomes the common end point to both types of AR.

Mortality

• Acute AR has a high mortality due to sudden uncompensated cardiovascular changes usually requiring immediate surgical management. • Chronic AR mortality relates to eventual decompensation of the LV and may occur at any age usually with severe AR. Decreased ejection fraction and LV function has a poor prognosis for recovery even after repair. • Yearly mortality risk relates to NYHA classification for chronic severe AR: – Asymptomatic: 2.8% – NYHA Class I: 3.0% – NYHA Class II: 6.3% – NYHA Class III–IV: 24.6% (4) ETIOLOGY/RISK FACTORS

• Male gender has a greater risk for AR with a related increased risk of hypertension, connective tissue and congenital valvular diseases, which may result in presentation at a younger age. • Severe AR is most commonly diagnosed at age 60 and above.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Acute AR results in an acute increase in LV diastolic volume, decreased aortic diastolic pressure (forward flow), decreased coronary perfusion pressure, volume overload, and decreased diastolic function of the LV. This leads to an increase in myocardial demand, acute fulminant CHF, and cardiogenic shock. Common causes of acute AR, including aortic dissection, warrant emergent surgical repair. • Chronic AR has a more insidious onset and may take years to become symptomatic. As regurgitant volume and AR worsen over time, the LV has time to remodel with eccentric hypertrophy and dilation. The increase in diastolic volume is compensated by the enlarged LV, increased heart rate, and decreased systemic vascular resistance (SVR). Ejection fraction is maintained and may prevent symptoms without exertion or positional changes. As time passes, the ventricle becomes “too enlarged” with resultant increases in wall stress and decreases in myocardial perfusion (leads to diminished EF, CHF, and end-organ hypoperfusion). Recall Laplace’s law where Tension = (Pressure × Radius)/Wall Thickness; as the radius increases, tension also increases (increases myocardial oxygen consumption). Sympathetic stimulation increases SVR to maintain pressure but worsens AR; hinders forward flow. Without timely surgical repair the heart may not be able to significantly recover.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintenance of cardiac output, coronary perfusion, and prevention of cardiac decompensation are the primary goals. • Normal sinus rhythm and avoidance of bradycardia to minimize regurgitant time

• SVR may be mildly decreased, but should be balanced between facilitating forward flow (decreasing regurgitation) and maintaining adequate coronary and systemic perfusion pressure. • Careful fluid management and inotropic support to prevent cardiovascular overload or collapse

PREOPERATIVE ASSESSMENT SYMPTOMS

• Chronic AR may be asymptomatic for decades. • Palpitations and tachycardia • Fatigue • Dyspnea on exertion • Orthopnea • Paroxysmal nocturnal dyspnea • Angina

History

• Family history of cardiac valvular disease, collagen or connective tissue disease, or congenital malformations • History of rheumatic disease or risk factors for endocarditis • Commonly diagnosed after symptomatic exercise or during workup for diastolic or systolic CHF • May be discovered early after detailed physical exam and auscultation of heart murmur • Usually classified by echocardiographic measurement of color Doppler flow across the valve

Signs/Physical Exam

• Syncope • Cyanosis • Decrescendo diastolic murmur • Watson’s hammer pulse (bounding pulse) • Corrigan’s carotid pulse • Wide pulse pressure • Signs of CHF

TREATMENT HISTORY

• Medical management of angina, CHF, diabetes, hypertension, and hyperlipidemia, if associated • Previous history of balloon aortic valvuloplasty or valve replacement • Previous treatment of infective endocarditis • Transesophageal echocardiography for diagnosis and risk stratification

MEDICATIONS

• Antihypertensives including calcium channel blockers; beta-blockers are usually not prescribed since they may cause bradycardia.

• Anti-anginals including nitrovasodilators • Heart failure treatments including digoxin, ACEI/ARB, and diuretics • Statin therapy if indicated

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Basic metabolic profile: Monitoring electrolytes and kidney function • CBC: Monitoring for preoperative infection and hematocrit and platelet counts adequate for surgery • CXR: Cardiopulmonary status • CT scan for evaluation of aorta • Echocardiogram: Diagnosis and classification of disease severity and ventricular function • Basic coagulation studies: Adequate levels for surgery and evaluation of liver function

CONCOMITANT ORGAN DYSFUNCTION

• Dilated cardiomyopathy and diastolic dysfunction • Concomitant mitral stenosis or regurgitation in rheumatic heart disease • Pulmonary hypertension, congestion, and pleural effusion • Renal insufficiency • Hypertension

CIRCUMSTANCES TO DELAY/ CONDITIONS • Unrelated end-organ failure • Recent myocardial infarction or stroke

CLASSIFICATIONS

Severe AR criteria: • >60 mL regurgitant volume • >50% regurgitant volume • Effective regurgitant orifice area >0.3 cm2 • Color Doppler Vena Contracta >0.6 cm • Regurgitant jet >60% of LVOT diameter • Aortic valve pressure half-time <250 ms • Early closure of mitral valve and LV dilation

TREATMENT PREOPERATIVE PREPARATION Premedications

Midazolam to prevent anxiety and increased sympathetic tone, as appropriate Special Concerns for Informed Consent

Risk for intraoperative stroke, myocardial infarction, and death should be discussed.

INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on the procedure; sedation, general (endotracheal tube or laryngeal mask airway) and regional anesthesia may be utilized. • Neuraxial techniques can result in a sympathectomy and facilitate forward flow (reduce regurgitation), but may reduce coronary perfusion pressure.

Monitors

• Standard ASA monitors • Invasive monitors may be chosen based upon the severity of AR and the surgical procedure.

Induction/Airway Management

• Smooth, controlled induction to maintain vital signs within normal limits • Anticholinergic medications may be administered to maintain a NSR and slightly increase the heart rate.

Maintenance

• Volatile and/or intravenous anesthetics may be utilized. Reductions in SVR are desirable to facilitate forward flow; however, adequate cerebral and coronary perfusion should be ensured. Total intravenous techniques may be associated with bradycardia, particularly if utilizing high doses of remifentanil. • Fluid balance includes maintaining normal preload and hematocrit >24–30 g/dL to optimize forward flow and myocardial oxygen balance. Excessive preload may add to regurgitant volume and cause LV failure.

Extubation/Emergence No additional concerns

FOLLOW-UP BED ACUITY

Depends on surgical procedure and severity of underlying disease MEDICATIONS/LAB STUDIES/CONSULTS

Standard postoperative fluid and electrolyte management and related laboratory studies COMPLICATIONS

Perioperative arrhythmia

REFERENCES

1. Odili AN, Amusa GA. Aortic aneurysm with valvular insufficiency: Is it due to Marfan syndrome or hypertension? A case report and review of literature. J Vasc Nurs. 2011;29(1):16–22.

2. Singh JP, Evans JC, Levy D, et al. Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation. Am J Cardiol. 1999;83:897–902. 3. Maurer G. Aortic regurgitation. Heart. 2006;92(7):994–1000.

4. Dujardin KS, Enriquez-Sarano M, Schaff HV, et al. Mortality and morbidity of aortic regurgitation in clinical practice: A long-term follow-up study. Circulation. 1999;99(14):1851–1857.

ADDITIONAL READING

• 2006 American College of Cardiology/American Heart Association Guidelines • Van Dyck MJ, Watremez C, Boodhwani M, et al. Review articles: Transesophageal echocardiographic evaluation during aortic valve repair surgery. Anesth Analg. 2010;111:59–70.

CODES ICD9

• 395.1 Rheumatic aortic insufficiency • 424.1 Aortic valve disorders • 746.4 Congenital insufficiency of aortic valve ICD10 • I35.1 Nonrheumatic aortic (valve) insufficiency • I06.1 Rheumatic aortic insufficiency • Q23.1 Congenital insufficiency of aortic valve

CLINICAL PEARLS

• Aortic regurgitation (AR) is most commonly an acquired disease but may be related to congenital malformations and several systemic conditions such as Marfan syndrome. • Significant signs and symptoms include shortness of breath, angina, syncope, and systolic and diastolic congestive heart failure with eccentric hypertrophy and a dilated LV. • Severity is classified by echocardiographic criteria; 60 mL or 50% regurgitant volume being severe AR. • Acute AR is life-threatening and often requires immediate surgical management. • Chronic AR requires medical or surgical management and may be asymptomatic until late stages. Symptomatic, severe AR with below normal LV EF requires urgent treatment and has poorer prognosis.

AORTIC STENOSIS Brian L. Marasigan, MD

BASICS DESCRIPTION

• The aortic valve normally consists of 3 leaflets which open during ventricular systole with an area of >2.5 cm2 and close during diastole. Since the aortic valve is the smallest area through which blood leaves the heart, its diameter determines maximum blood flow. • Aortic valve stenosis is a narrowing of this area at the valve itself. New recommendations classify severe aortic stenosis (AS) as an area <1.0 cm2 with a transvalvular mean gradient >40 mm Hg, although symptoms may begin at much earlier stages. It is the most common valvular lesion in the US.

EPIDEMIOLOGY Prevalence

• Congenital AS occurs in 4–8 per 1,000 live births. • Congenitally bicuspid aortic valves occur in 1–2% of the US population and later in life accounts for 30–40% of AS. • >50% of AS is acquired.

Prevalence

Present in 2–4% of adults aged 65 years and older (1)[B].

Morbidity

• Risk for acute myocardial infarction, syncope, congestive heart failure (CHF), and endocarditis • Low-grade severe stenosis with preserved ejection fraction has similar outcomes to those with moderate stenosis (2)[B]. • Asymptomatic very severe AS (area <0.75 cm2) has a very poor prognosis and rapid deterioration; elective valve surgery should be considered (3)[A].

Mortality

• 9% mortality per year • Symptomatic AS sudden death risk is 15–20% with a 3-year mortality of 75%. • When symptoms of angina, syncope, or CHF are present, 50% mortality is seen at approximately 5, 3, and 2 years, respectively. ETIOLOGY/RISK FACTORS

• Age <70 years: The etiology of AS is more commonly rheumatic or bicuspid aortic valve disease. • Age >70 years: The etiology of AS is more commonly calcific AS.

• Risk factors are similar to vascular disease and may include hyperlipidemia, hypertension, and diabetes.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The basic pathophysiology of AS stems from obstruction of cardiac output with a highly resistant valve opening. As the stenosis becomes more severe, the left ventricle (LV) compensates with concentric hypertrophy to overcome the increasing afterload/tension; stroke volume is maintained. Additionally, cardiac output becomes fixed and highly dependent upon heart rate and filling (diastolic dysfunction). • Myocardial oxygen supply and demand – Supply decreases from: A thickened myocardium (coronary blood flow must perfuse/penetrate), increased left ventricular end diastolic pressure (decreased coronary diastolic perfusion pressure), and limited cardiac output. – Demand increases from: A thickened myocardium (more muscle equals increased energy consumption) and increased afterload. • Over time, systolic function can decrease as the LV decompensates and dilates or becomes ischemic. Ventricular systolic and diastolic dysfunction can lead to pulmonary congestion and CHF. Additionally, sympathetic tone increases and may contribute to symptoms. • A slow heart rate is desired to allow time for forward flow after an adequate LV pressure has been attained. Maintaining a sinus rhythm is necessary, as LV hypertrophy impairs filling and the atrial kick is needed to maintain adequate LV end diastolic volume (preload). • Both normal and congenitally bicuspid valves undergo degeneration through which scarring, calcification, and sclerosis become the most common cause of acquired AS.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintenance of cardiac output, coronary perfusion (diastolic perfusion pressure), normal sinus rhythm, volume status, and prevention of cardiac decompensation are the primary goals. • Inotropic support may be necessary to prevent cardiovascular overload or collapse.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Severity of symptoms may be classified by NYHA I–IV. Early symptoms often include exertional shortness of breath. – Anginal pain may be an early symptom and may occur in the absence of coronary occlusion. – Syncope may occur due to a decrease in cardiac output and exertional systemic vasodilation. – CHF is often a late sign that signifies severe valve stenosis or cardiomyopathy.

History

• Commonly diagnosed after symptomatic exercising or during workup for diastolic or systolic CHF • May be discovered early after detailed physical exam and heart auscultation

Signs/Physical Exam

• Crescendo–decrescendo systolic murmur and decreased S2 sound • Pulsus parvus et tardus with narrow pulse pressure • Signs of CHF and increased sympathetic tone

TREATMENT HISTORY

Previous history of balloon aortic valvuloplasty or valve replacement MEDICATIONS

• Antihypertensives including beta-blockers and calcium channel blockers • Anti-anginals including nitrovasodilators • Heart failure treatments including digoxin, ACEI/ARB, and diuretics • Statin therapy

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Basic metabolic profile to monitor electrolytes and kidney function; aids with perioperative management • CBC: WBC to monitor for infection; Hct and platelet counts should be adequate for surgery. • CXR to assess cardiopulmonary status • Echocardiogram for diagnosis and classification of disease severity (valve area, transvalvular gradient) and ventricular function • Basic coagulation studies to evaluate liver function

CONCOMITANT ORGAN DYSFUNCTION

• Cardiac: LV hypertrophy, diastolic dysfunction, hypertension, aortic regurgitation (due to poor valve closure), mitral stenosis, or regurgitation in rheumatic heart disease • Pulmonary: Hypertension, congestion, and pleural effusion • Renal insufficiency

CIRCUMSTANCES TO DELAY/ CONDITIONS • Decompensated CHF • Sepsis or infection • Unrelated end-organ failure • Recent myocardial infarction or stroke

CLASSIFICATIONS

• AS severity by valve area: – >2.5 cm2: Normal – 1.5–2.0 cm2: Mild stenosis – 1.0–1.5 cm2: Moderate stenosis – <1.0 cm2: Severe stenosis • AS severity by mean pressure gradient: – <25 mm Hg: Mild stenosis

– 25–40 mm Hg: Moderate stenosis – >40 mm Hg: Severe stenosis

TREATMENT PREOPERATIVE PREPARATION Premedications

Benzodiazepines may be useful to prevent anxiety and tachycardia; however, they should be titrated cautiously to avoid sympatholysis. Special Concerns for Informed Consent

• Risk for intraoperative stroke, myocardial infarction, and death should be discussed. • Arterial line placement if needed

INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on the procedure: Sedation, general (endotracheal tube or laryngeal mask airway) and peripheral nerve blocks may be utilized. • Neuraxial techniques can result in a sympathectomy and decreased systemic vascular resistance (SVR) that can impair coronary perfusion. This technique may be considered in mild or moderate AS. Epidurals can allow for slower bolusing, time for fluid loading, and treatment of hypotension with vasopressors (phenylephrine). Monitors

• Standard ASA monitors • 5-lead EKG for arrhythmia and ischemia • Arterial line for beat-to-beat BP monitoring • Invasive monitors may be chosen based upon the severity of AS and the surgical procedure.

Induction/Airway Management

A smooth, controlled induction should be performed to maintain vital signs within normal limits (heart rate and SVR) and allow time for treatment. Maintenance

• Volatile anesthetics, intravenous, or a combination may be utilized. The goal should be to maintain normal sinus rhythm and SVR. – Total intravenous anesthesia with propofol and high-dose narcotics can result in bradycardia and hypotension; consider concurrent phenylephrine, ephedrine, or an anticholinergic. – Volatile agents can decrease SVR and myocardial contractility; consider concurrent phenylephrine. • Preload. Because stroke volume is fixed, adequate filling volumes are essential in maintaining a stable cardiac output. For patients at risk for ischemic events, hematocrit values may also be of concern.

• Rhythm, rate, blood pressure – Normal sinus rhythm may be maintained by minimizing cardiac stress and avoiding proarrhythmic drugs – Slight bradycardia may improve coronary perfusion time and LV filling but may decrease total cardiac output (stroke volume is fixed). Conversely, tachycardia increases myocardial oxygen consumption along with decreases in LV filling time and diastolic coronary perfusion time. Caution should be exercised when using powerful chronotropes or anticholinergics. – Hypotension and hypertension should be managed with rate and rhythm in mind. All inotropes and vasopressors may be used with caution. • Ischemia usually occurs with arrhythmia, tachycardia, or hypotension, and the treatment usually lies in the reversal of those conditions.

Extubation/Emergence

• Avoid tachycardia and hypotension • Use standard extubation criteria

FOLLOW-UP BED ACUITY

Depends on surgical procedure, severity of underlying disease, and intraoperative events MEDICATIONS/LAB STUDIES/ CONSULTS

Cardiology consult may be considered in severe disease if ischemic events occurred intraoperatively. COMPLICATIONS

• Perioperative arrhythmia • Mental status changes and stroke • Myocardial infarction

REFERENCES

1. Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: Pathogenesis, disease progression, and treatment strategies. Circulation. 2005;111(24):3316–3326. 2. Jander N, Minners J, Holme I, et al. Outcome of patients with low gradient “severe” aortic stenosis and preserved ejection fraction. Circulation. 2011;123(8):887–895. 3. Rosenhek R, Zilberszac R, Schemper M, et al. Natural history of very severe aortic stenosis. Circulation. 2010;121(1):151–156.

ADDITIONAL READING

• Andritsos M, Singh N, Patel P, et al. The year in cardiothoracic and vascular anesthesia: Selected highlights from 2010. J Cardiothorac Vasc Anesth. 2011;25(1):6–15.

See Also (Topic, Algorithm, Electronic Media Element) • Aortic regurgitation • Aortic valve replacement

CODES ICD9 • 395.0 Rheumatic aortic stenosis • 424.1 Aortic valve disorders • 746.3 Congenital stenosis of aortic valve ICD10

• I35.0 Nonrheumatic aortic (valve) stenosis • Q23.0 Congenital stenosis of aortic valve • I06.0 Rheumatic aortic stenosis

CLINICAL PEARLS • Severity is classified by valve area and transvalvular gradients; values <1.0 cm2 and a mean pressure gradient of 40 mm Hg indicate severe AS. • Maintenance of general anesthesia includes supporting cardiac systolic function, optimizing fluid management, sustaining normal sinus rhythm, and monitoring for ischemia.

AORTIC VALVE REPLACEMENT Sascha Beutler, MD, PhD Daniel Castillo, MD

BASICS DESCRIPTION General

• Aortic valve replacement is an open, intracardiac surgery procedure in which the stenotic or regurgitant aortic valve is replaced with a healthy valve. The 2 basic artificial heart valves are mechanical and tissues valves. • Following sternotomy, opening of the pericardium, and routine venous and arterial cannulation, the patient is taken onto full cardiopulmonary bypass (CPB). After the heart is arrested, the aorta is opened to expose the aortic valve. The valve leaflets are excised and the annulus is debrided. The annulus is then measured to properly match the prosthetic valve. Interrupted sutures are placed through the annulus for its entire circumference and then passed through the sewing ring. The prosthesis is tied securely in place. • Systemic rewarming is initiated during the final stages of the valve implantation, and the left ventricle is allowed to fill during aortic closure. With the patient in the head-down position, all remaining air is vented from the left heart and aorta. The cross-clamp is removed. • Pacing wires and chest tubes are placed and the patient is weaned from bypass. Once the patient is stable, decannulation and heparin reversal are accomplished in routine manner. • Concomitant root replacement may be necessary in patients with aortic stenosis secondary to bicuspid valve pathology and concurrent aortic root dilations. • Pulmonary autograft (Ross procedure) involves replacing the aortic valve with a pulmonary valve autograft and right-sided reconstruction with a homograft; it is used in children and adolescents. • Minimally invasive aortic valve surgery through smaller incisions with specialized instruments is being explored; for the surgery on the valve itself conventional instruments and techniques are used. – Only selected patients are eligible for these approaches. – Initial results are favorable in regard to clinical outcome, perioperative complications and cost. – No randomized controlled trials are available comparing minimally invasive and open surgery. • Transcatheter aortic valve replacement is a new catheter-approach that obviates the need for open heart surgery. It is being used in Europe and parts of the world, but only tested in clinical trials in the US. The results for high-risk patients with severe aortic stenosis who are not surgical candidates are promising (1)[B]. Position

• Supine, arms tucked • Temporary Trendelenburg at the time of left ventricle de-airing, prior to coming off bypass

Incision

• Standard: Median sternotomy • Alternative incision sites (e.g., right second intercostal anterior thoracotomy) are used as part of “minimally invasive aortic valve surgery.”

Approximate Time

4–8 hours, depending on the experience of the team and technical difficulties EBL Expected

• CPB machine leads to dilution. • Blood loss typically ranges from 1,000 to 2,000 mL.

Hospital Stay

Typical length of stay in the surgical ICU is 1–3 days and 3–7 days in the hospital overall. Special Equipment for Surgery

• Valve (mechanical or tissue) • CPB machine (operated by perfusionist) • Minimally invasive approaches require special equipment. • Transesophageal echocardiography probe (intraoperative examination performed by echo trained anesthesiologists or cardiologist)

EPIDEMIOLOGY Prevalence

In 2009 approximately 70,000 patients underwent aortic valve replacement in the US. Morbidity

• The 2008 ACC/AHA Valvular Disease guidelines refer to risk stratification models to estimate the risk of in-hospital mortality and morbidity of valve surgery with or without coronary artery bypass (2). All models have drawbacks such as estimating risk for only one specific procedure or not including patient’s variable like nutritional status. There are 3 major models: – The US-based registry by the Society of Thoracic Surgeons (STS) (3)[B]. It includes data from nearly 90% of cardiac surgery providers in the US and may provide the most accurate risk stratification for aortic valve replacement. – The European System for Cardiac Operative Risk Evaluation (“EuroScore") – The scoring system developed from Great Britain’s and Ireland’s national database

Mortality

• Varies significantly with age, comorbidities, type of valvular lesion, ventricular function, other concomitant valvular surgery, and/or bypass surgery • Risk stratification models are useful to predict mortality risk for the individual patient.

Example: Mortality <1% in a 65-year-old patient with symptomatic severe aortic stenosis, normal left ventricular function and otherwise healthy; however, mortality increases >1% for the same patient with hypertension and diabetes.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Hemodynamic stability from induction to the initiation of bypass. Management depends on: The type of lesion (stenosis vs. regurgitation), right and left ventricular function, pulmonary pressures, and other clinical factors. • After successful replacement and completion of bypass, the goal is to maintain adequate cardiac output and blood pressure; inotropes may be required if left ventricular function is depressed.

PREOPERATIVE ASSESSMENT SYMPTOMS

Vary depending on the type of lesion (stenosis vs. regurgitation) and the time course (acute vs. chronic) History

Determine if there is a history of esophageal strictures or other abnormality that would prohibit placement of transesophageal echocardiography during the procedure. Signs/Physical Exam

See “Aortic Stenosis” and “Aortic Regurgitation” chapters MEDICATIONS

• Medical management depends on the type of lesion and other comorbidities. • Initiation of statins may reduce the incidence of atrial fibrillation and mortality.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Preoperative transthoracic echocardiography and sometimes a transesophageal echocardiography are performed. • Coronary angiography is routinely performed since significant coronary artery disease is a common comorbidity and may require concurrent coronary bypass grafting.

CONCOMITANT ORGAN DYSFUNCTION

• Renal dysfunction; further deterioration may be precipitated by contrast dye used during catheterization (prior to the valve replacement) and increased bypass time. • Chronic pulmonary disease may acutely worsen secondary to bypass and lead to hypoxemia when coming off. • Pre-existing neurologic deficits put the patient at great risk for further mental status deterioration postoperatively.

TREATMENT PREOPERATIVE PREPARATION Premedications

Consider gentle anxiolysis with benzodiazepines Special Concerns for Informed Consent

Morbidity and mortality risks vary with the extent of surgery (e.g., coronary bypass surgery in addition to valve replacement) and pre-existing comorbidities. Antibiotics/ Common Organisms

Skin flora poses the greatest concern; cefazolin is utilized if the patient is not a carrier of multi-resistant bacteria and there is no allergy. It is administered intravenously within 60 minutes prior to incision and repeated q3–4h until chest closure. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia in the US • There are case reports of open heart surgery performed under epidural with sedation in other parts of the world. Monitors

• ASA standard monitoring; core and shell temperatures are measured. • Arterial line placement most often prior to induction; the absence of pulsatile blood flow during bypass precludes noninvasive blood pressure measurement. • Central venous access is usually obtained after induction; pulmonary artery catheter placement may be considered. • Transesophageal echocardiography is frequently used intraoperatively to guide and assess aortic valve replacement. Induction/Airway Management

• Goal is to provide hemodynamic stability throughout the induction period. Gentle propofol administration (with vasopressors and inotropes as needed) or etomidate in combination with fentanyl. • In the event of hemodynamic instability CPB may be instituted immediately.

Maintenance

• Patients are usually maintained with oxygen/volatile agents and intermittent doses of opioids and non-depolarizing muscle relaxants. • During bypass, volatile agent is added to the blood by the perfusionist through the bypass machine. • The management of patients during bypass varies substantially by institution and practitioner. • On bypass the target mean arterial blood pressure is typically between 50 and 80 mm▒Hg.

• On bypass the patient’s body temperature is cooled at the beginning and warmed to normal body temperature before termination of bypass.

Extubation/Emergence

• Patients remain intubated and are transferred to the ICU. • Sedation is typically provided with propofol or dexmedetomidine infusion. The latter appears to have a lower risk for the development of postoperative delirium.

FOLLOW-UP BED ACUITY

• Surgical ICU • The time to extubation varies from a few hours to 24 hours and even days, depending on the patient’s hemodynamic status, respiratory status, bleeding/coagulation, and other organ systems.

ANALGESIA

• Usually provided by intravenous opioids either as intermittent boluses or as continuous infusion until extubation • Once the patient is extubated and bowel function has returned, oral opioids can be given.

COMPLICATIONS

• Bleeding, reoperation, heart block (requires insertion of permanent cardiac pacemaker), stroke, renal failure, prolonged ventilation, infection; the incidence varies depending on preoperative status, length and type of operation. • Atrial fibrillation • Replacement of a diseased heart valve with a prosthetic valve exchanges the native disease for complications that are unique to the prosthetic valve. – Structural failure, though not uncommon with bioprosthesis, is very rare with mechanical valves. – Severe and recurrent bleeding due to anticoagulant therapy: Mechanical valves require long-term anticoagulation therapy, most often with warfarin, while patients with bioprosthetic valves usually receive anticoagulation with warfarin only for 6 weeks to 3 months postoperatively and then aspirin lifelong. – Valvular thrombosis and thromboembolic events, especially in patients with mechanical valves and inadequate anticoagulant therapy – Severe hemolysis is seen mostly with mechanical valves – Endocarditis • Complications associated with open heart surgery and CPB

PROGNOSIS

As survival after a first valve replacement has improved, more patients require a second operation for replacement (about 2–3% during the first 10 years).

REFERENCES

1. Leon MB, Smith CR, Mack M. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363(17):1597–1607. 2. Bonow RO, Carabello BA, Chatterjee K, et al. Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2008;118:e523–e661. 3. Shahian DM, O’Brien SM, Filardo G, et al. The Society of Thoracic Surgeons 2008 cardiac surgery risk models. Part 2: Isolated valve surgery. Ann Thorac Surg. 2009;88:S23–S42.

ADDITIONAL READING

• Tabata M, Umakanthan R, Cohn LH, et al. Early and late outcomes of 1000 minimally invasive aortic valve operations. Eur J Cardiothorac Surg. 2008;33:537–541. • www.sts.org/quality-research-patient-safety/quality/risk-calculator-and-models/riskcalculator • www.euroscore.org • www.ucl.ac.uk/research/riskmodel/index.html See Also (Topic, Algorithm, Electronic Media Element) • Aortic valve stenosis • Aortic valve regurgitation • Cardiopulmonary bypass

CODES ICD9 • V42.2 Heart valve replaced by transplant • V43.3 Heart valve replaced by other means ICD10 • Z95.2 Presence of prosthetic heart valve • Z95.3 Presence of xenogenic heart valve • Z95.4 Presence of other heart-valve replacement

CLINICAL PEARLS

• Aortic valve replacement is an open, intracardiac surgery requiring CPB. The standard approach is a median sternotomy; newer minimally invasive techniques are on the rise. • Risk stratification models can help predict mortality and morbidity for the individual patient. • There is a significant rate of structural failure of bioprosthetic valves within the first 10–15 years that can require reoperation.

AORTOCAVAL COMPRESSION OF PREGNANCY Kanishka Monis, MD Poovendran Saththasivam, MD

BASICS DESCRIPTION

• Aortocaval compression refers to compression of the aorta and inferior vena cava (IVC) by the gravid uterus. • Supine hypotension syndrome describes the development of rapid hypotension or cardiovascular collapse after placing the patient in a supine position with rapid recovery in the lateral, sitting, or standing position. Classic signs and symptoms include bradycardia, pallor, sweating, dizziness, and nausea. EPIDEMIOLOGY Prevalence

• 100% of parturients experience some degree of aortocaval compression at term. • Approximately 15% of parturients experience supine hypotension syndrome at term.

Morbidity/Mortality

Compression of the aorta can lead to a decrease in uteroplacental perfusion and fetal hypoxemia. ETIOLOGY/RISK FACTORS

• Supine position • Multiple gestations • Obesity • Polyhydramnios • Uterine myomata (“fibroid tumors”) • Fetal breech presentation, transverse and oblique, increases the risk of aortocaval compression. PHYSIOLOGY/PATHOPHYSIOLOGY

• Venous: Compression of the IVC leads to a decrease in venous return and an increase in lower extremity venous pressure. – The decreased preload can result in a 10–20% decline in stroke volume and cardiac output. – Blood return via collaterals (intraosseous vertebral veins, paravertebral veins, and epidural veins) is less than would occur through the IVC. • Aorta: Compression of the abdominal aorta can cause a decrease in peripheral perfusion. – Uteroplacental insufficiency may be secondary to decreased perfusion pressure, and can present as decelerations on the fetal heart monitor.

• Uterine contractions and fetal descent during labor typically reduce the risk of aortocaval compression. However, there have been some case reports of aortocaval compression occurring during labor and the postpartum period.

PREVENTATIVE MEASURES

• Avoid the supine position: – A full lateral position minimizes aortocaval compression. – A left uterine displacement (with a pelvic wedge or table tilt) may be reduced to 15° to improve comfort or facilitate Cesarean delivery. – Flexing of the legs may decrease lumbar lordosis, thus reducing vena cava compression. – Crossing one leg over the other tilts the pelvis and can relieve vena cava compression. • Ensure adequate intravascular volume and vascular tone; aortocaval compression is enhanced during periods of maternal hypotension. • The speed of delivering the fetus is important if a Cesarean section is planned. Minimize any delays and consider a wedge or table tilt.

PREOPERATIVE ASSESSMENT • The severity of the aortocaval compression is greatest at about 38 weeks and decreases after the engagement of the fetal head into the maternal pelvis. • The onset of the symptoms is usually rapid (average of 3–10 minutes). • The syndrome is initiated by placing the patient in the supine position. • Maternal heart rate is invariably increased in most cases. Maximum heart rate or abrupt bradycardia can ensue just before syncope. • Fetal heart tones will often demonstrate decelerations that signify fetal distress. • Symptoms: – Dyspnea – Nausea/vomiting – Diaphoresis – Dizziness – Anxiety/agitation – Loss of consciousness • Signs: – Maternal tachycardia or bradycardia – Hypotension – Pallor/cyanosis – Cold clammy skin – Non-reassuring fetal heart tracing – Distension of lower extremity veins

DIFFERENTIAL DIAGNOSIS

• Pulmonary thromboembolism • Amniotic fluid embolism • High neuraxial block • Uterine rupture

• Placental abruption • Myocardial infarction

TREATMENT • Lateral position or left uterine displacement (LUD): Some parturients may still experience supine hypotension syndrome in LUD. • Fluid boluses can minimize aortocaval compression. • Vasopressor boluses (phenylephrine or ephedrine) for treatment of hypotension

FOLLOW-UP • Parturients in late pregnancy should be advised to recognize the symptoms of aortocaval compression and avoid lying supine. • The anesthesia provider should be vigilant and prepared to recognize aortocaval compression in parturients who are placed in the supine position. In particular, placement of a laboring epidural and bolusing can result in hypotension (sympatholysis) and enhance the effects of compression.

ADDITIONAL READING

• Cyna AM, Andrew M, Emmett RS, et al. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev. 2006;4:CD002251. • Kinsella SM, Lohmann G. Supine hypotensive syndrome. Obstet Gynecol. 1994;83(5 Pt 1):774–788. • Levy DM. Emergency caesarean section: Best practice. Anaesthesia. 2006;61(8):786–791. • Ngan Kee WD. Prevention of maternal hypotension after regional anaesthesia for cesarean section. Curr Opin Anaesthesiol. 2010;23(3):304–309.

See Also (Topic, Algorithm, Electronic Media Element) • Cardiovascular physiology in pregnancy • Preload • Fetal heart tones

CODES ICD9 • 459.2 Compression of vein • 671.80 Other venous complications of pregnancy and the puerperium, unspecified as to episode of care or not applicable • 671.81 Other venous complications of pregnancy and the puerperium, delivered, with or without mention of antepartum condition ICD10

• I87.1 Compression of vein • O22.8X9 Other venous complications in pregnancy, unsp trimester • O22.8X1 Other venous complications in pregnancy, first trimester

CLINICAL PEARLS

• Aortocaval compression is present after 20 weeks gestation and reaches its maximum effect at 38 weeks gestation. • Aortocaval compression is lessened once the fetal head is engaged in the pelvis. • Supine hypotension syndrome manifests as profound hypotension and bradycardia. • Uteroplacental insufficiency caused by compression of the aorta can manifest via a nonreassuring fetal heart tracing. • Lateral position or left uterine displacement relieves aortocaval compression.

APNEA OF PREMATURITY Joel Stockman, MD Samuel H. Wald, MD

BASICS DESCRIPTION

• Apnea of prematurity (AOP) is defined as the cessation of breathing in premature infants which lasts for: – >20 seconds, or – >10 seconds if associated with bradycardia (<80 beats per minute [bpm]) or oxygen desaturation (O2 saturation <80–85%) • It is categorized as central, obstructive, or mixed, with mixed apnea making up the majority of cases (1)[C].

EPIDEMIOLOGY Prevalence

• >50% of preterm infants have clinically significant apnea, bradycardia, or oxygen desaturation, with a peak incidence occurring between 5 and 7 days after birth (2)[C]. – Essentially affects all neonates weighing <1,000 g at birth (1)[C] • Incidence is inversely related to gestational age and postconceptual age. – Postoperative risk is <5% at a postconceptual age of 48 weeks and gestational age of 35 weeks. – Postoperative risk is <1% at a postconceptual age of 56 weeks with a gestational age 32 weeks or postconceptual age of 56 weeks and gestational age of 32 weeks (3)[A]. Prevalence

• Significant AOP will resolve by 40 weeks postconceptual age for a majority of those infants at risk (1)[C]. • Of note, most severely premature infants (24–28 weeks gestation) may have apnea persisting beyond 40 weeks postconceptual age (4)[C].

Morbidity

AOP is seen in most high-risk neonates, so there is great difficulty in separating its effects from the consequences of prematurity. However, it is thought to increase the incidence of intraventricular hemorrhage (IVH), hydrocephalus, prolonged mechanical ventilation, and abnormal neurologic development after the 1st year of life (5)[C].

Mortality

No direct correlation found

ETIOLOGY/RISK FACTORS

• An associated risk factor for postsurgical apnea is the presence of an apneic episode at home. • Anemia (hemoglobin <10 g/dL) is a significant risk factor, especially for neonates >43 weeks postconceptual age (3)[A]. PHYSIOLOGY/PATHOPHYSIOLOGY

• AOP reflects the immaturity of the respiratory control system, which manifests as an unstable respiratory rhythm. The neonatal neurotransmission pathway is underdeveloped, and both central and peripheral chemoreceptors are impaired. – The preterm neonate’s ventilatory response to hypercapnia is significantly reduced. – Preterm infants express a biphasic response to hypoxia, with the initial response being an increase in ventilation for 1 minute, followed by a phase of decreased ventilation. Severely preterm infants typically do not display a period of hyperventilation. – There is an enhanced inhibitory response by upper and lower airway afferent innervation secondary to stimulation (i.e., negative pressure and positive airflow) (6).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Sedative drugs/anesthetic agents create a significant risk for development of apnea. • At-risk infants must be admitted and monitored in the immediate postoperative setting.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Cessation of breathing for more than 20 seconds • Cessation of breathing for more than 10 seconds if accompanied by: – Bradycardia (>30 bpm below resting heart rate) – Oxygen saturation <85% for >5 seconds

History

• Discuss presence of apneic events with the bedside caregivers to note severity • Assess other comorbidities related to the premature infant • Note the current duration of ventilatory support

Signs/Physical Exam

• Observe respiratory effort • Assess for any upper airway abnormalities • Assess for conditions that may affect breathing (e.g., neurologic disorders, pulmonary disorders, CHD)

TREATMENT HISTORY

• History of mechanical ventilation/support • Methylxanthines (e.g., caffeine, theophylline) administration.

MEDICATIONS

• Methylxanthines are the mainstay of treatment.

– These drugs are thought to stimulate breathing efforts by an unknown mechanism (may be due to increased chemoreceptor responsiveness, enhanced respiratory muscle performance, and generalized nervous system excitation). – Adverse effects include feeding intolerance and tachycardia. – Effective in reducing apneic episodes and ventilator use in the first 2–7 days of treatment – Caffeine is the Preferred Drug Due to its lower toxicity (7)[A].

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC – A hemoglobin level <10 g/dL increases the risk of apnea to greater than the mean for infants of all postconceptual ages (3)[A]. • Electrolyte panel

CONCOMITANT ORGAN DYSFUNCTION

• Respiratory distress syndrome • Infections • Hypoglycemia • Neurologic dysfunction (e.g., IVH, hydrocephalus, stroke)

CIRCUMSTANCES TO DELAY/ CONDITIONS

• These infants should be cared for in an environment that has the capability to provide continuous postoperative cardiorespiratory monitoring. • Institutional practices may vary, but recommendations exist to delay elective cases up to 60 weeks postconceptual age. Clinicians must weigh the risk for unrecognized apnea versus the cost savings through avoidance of overnight admission.

CLASSIFICATIONS

• Spontaneous: – Minimal physiologic changes – Events of brief duration and associated with self-recovery – Events occurring once or twice in 24 hours • Mild/moderate: – Events involving apnea, bradycardia, and/or oxygen desaturation of intermediate duration • Severe: – Events of clinical significance with persistent bradycardia and oxygen desaturation – Requires vigorous stimulation, oxygen administration, and/or assisted ventilation (2)[C]

TREATMENT PREOPERATIVE PREPARATION Premedications

• Consider: – Atropine 10 mcg/kg

– Caffeine 10 mg/kg

Special Concerns for Informed Consent

• Need for possible continued postoperative intubation and ventilation • Need for postoperative apnea monitoring – Minimum observation period of 12–24 hours for those infants at increased risk

INTRAOPERATIVE CARE Choice of Anesthesia

• Less oxygen desaturation/bradycardia is associated with procedures completed under regional anesthesia (spinal/caudal) and without sedation (8)[A]. • Use short-acting anesthetic agents • Minimize long-acting intravenous and oral anesthetics

Monitors

• Standard ASA monitors • Appropriate IV access

Induction/Airway Management

Dictated by the patient’s comorbidities Maintenance

Any form of sedation/general anesthesia carries an increased risk of postoperative apnea. Extubation /Emergence

• Ensure the full reversal of muscle relaxant • The preterm infant should be completely awake and vigorous prior to extubation.

FOLLOW-UP BED ACUITY

Discharge to a monitored, inpatient unit for 12–24 hours MEDICATIONS/LAB STUDIES/ CONSULTS

Postoperative respiratory support may be necessary, depending on the type of surgery. COMPLICATIONS

Preterm infants may have a history of prior intubation and thus are at an increased risk for subglottic stenosis.

REFERENCES

1. iner NN, Higgins R, Kattwinkel J, et al. Summary proceedings from the apnea-ofprematurity group. Pediatrics. 2006;117:S47–S51. 2. Mayock DE. Apnea. University of Washington Division of Neonatology, 2011. Available at:

http://depts.washington.edu/nicuweb/NICU-WEB/apnea.stm 3. Cote CJ, Zaslavsky A, Downes JJ, et al. Postoperative apnea in former preterm infants after inguinal herniorrhaphy: A combined analysis. Anesthesiology. 1995;82(4):809–822.

4. Baird TM, Martin RJ, Abu-Shaweesh JM. Clinical associations, treatment, and outcome of apnea of prematurity. NeoReviews. 2002;3:66–70. 5. Butcher-Puech MC, Henderson-Smart DJ, Holley D. Relation between apnea duration and type and neurological status of preterm infants. Arch Dis Child. 1985;60(10):953–958. 6. Mathew OP. Apnea of prematurity: Pathogenesis and management strategies. J Perinatol. 2010:1–9. 7. Henderson-Smart DJ, Steer PA. Methylxanthine treatment for apnea in preterm infants. Cochrane Database Syst Rev. 2001;3:CD000140.

8. Krane EF, Haberkern CM, Jacobson LE. Postoperative apnea, bradycardia, and oxygen desaturation in formerly premature infants: Prospective comparison of spinal and general anesthesia. Anesth Analg. 1995;80:7–13. See Also (Topic, Algorithm, Electronic Media Element)

• Pediatric respiratory physiology • Caudal epidural

CODES ICD9 770.81 Primary apnea of newborn ICD10 P28.3 Primary sleep apnea of newborn

CLINICAL PEARLS

• The risk of AOP is inversely correlated to postconceptual age. • The anesthetic should be tailored to the use of agents with the least respiratory depression. • Postoperative intubation may be necessary in high-risk patients. • Inpatient admission and/or postoperative respiratory monitoring are highly recommended in at-risk patients.

APPENDECTOMY Emily L. Drennan, MD

BASICS DESCRIPTION General

• Appendicitis is caused by an obstruction of the appendiceal lumen and can result in inflammation, edema, and the potential for rupture of the viscus. • Appendectomy is a surgical procedure that can be performed, open or laparoscopically, to remove the appendix when infection and/or inflammation are suspected or present. Removal is undertaken to avoid the complication of a ruptured appendix with resultant peritonitis. • Laparoscopic appendectomies are primarily performed today. Following trochar insertion and the establishment of a pneumoperitoneum, the cecum is identified and retracted in order to mobilize the appendix. An incision or window is made into the mesoappendix prior to clamping and ligating the base. The appendix may be removed through the trochar or placed into a bag depending on its size. Benefits over an open procedure include: Less postoperative pain, smaller incisions (better cosmetic result), and reduced length of stay. Drawbacks include: Greater cost, potentially longer operative time, and requirement of general anesthesia due to insufflation. • Open appendectomy involves adequate exposure of the cecum, followed by pulling of the cecum through the incision site to expose the attached appendix. The base is clamped and cut and drains are inserted prior to wound closure. – Laparoscopic cases may be converted to open when operating conditions are suboptimal for laparoscopy. – It is commonly performed for complicated appendicitis or patients with extensive previous intra-abdominal surgeries. – May be performed under regional anesthesia for patients who are at high risk for complications of general anesthesia (e.g., pregnancy, pulmonary hypertension). Position

• Open: Supine with arms out or tucked • Laparoscopy: Supine with arms tucked; surgeon stands on the left side of the patient. Rightward tilt of the bed and Trendelenburg position may facilitate surgical exposure. Incision

• Laparoscopy: 1 cm incision at the umbilicus, and two to three 5 mm incisions in the lower abdomen for the insertion of trochars. • Open: Transverse right lower quadrant incision (McBurney or Rockey-Davis)

Approximate Time

15–60 minutes for either approach EBL Expected

Less than 75 mL Hospital Stay

• 24 hours for uncomplicated appendicitis • Ruptured or otherwise complicated appendicitis has an average length of stay of 5 days.

Special Equipment for Surgery Laparoscopy equipment EPIDEMIOLOGY Prevalence

• In the US, ~250,000 cases of appendicitis annually • Most common in 10–19 year olds

Prevalence

In the US, approximately 7% of people are affected at some point in their lives. Morbidity

Varies from 5% to 11% and is related to the perforation of the appendix and degree of peritonitis Mortality

• Overall rate of 0.2–0.8% related to appendicitis, not surgical intervention • Rate following appendectomy: 0–0.2% • Elderly have the highest mortality rate.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Consider preoperative nasogastric tube placement to decompress the stomach • Patient may be hypovolemic from vomiting and/or poor PO intake. • Counsel pregnant patients about the risk for preterm labor; discuss the option of an open procedure with neuraxial anesthesia.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Abdominal pain • Anorexia • Nausea • Emesis

History

Periumbilical pain that migrates to the right lower quadrant (RLQ) is present in

approximately 50% of cases. Signs/Physical Exam

• RLQ pain, tenderness • Guarding, rebound on abdominal exam • Pain with rectal exam • Psoas sign; inflammation from retrocecal appendix • Palpation of the mass in the RLQ

MEDICATIONS

Antibiotic therapy may be considered for nonsurgical candidates, such as those with severe lung disease or recent myocardial infarction. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• KUB, ultrasound, and/or CT scan have reduced the incidence of “normal” appendixes mimicking appendicitis. • WBC count with differential • Beta-HCG, to rule out ectopic pregnancy as a cause of pain in females • Concomitant organ dysfunction may necessitate additional preoperative assessment such as EKG, basic metabolic panel, etc. Pregnancy Considerations

• Most common general surgery intervention during pregnancy with an incidence of 0.06– 0.1% • Preoperative diagnosis is difficult in the setting of pregnancy. Additionally, the gravid patient has an elevated WBC at baseline. • An ultrasound diagnosis is preferred over CT scan to avoid radiation exposure. • The appendix is located at the umbilical level in the second trimester and the RUQ in the third trimester. • 4% risk of pregnancy loss, 7% risk of early labor and delivery related to appendectomy

TREATMENT PREOPERATIVE PREPARATION Premedications

• GI prophylaxis including a H2 blocker, non-particulate antacid, and possibly a pro-motility agent • Preoperative hydration and electrolyte repletion, as needed

Special Concerns for Informed Consent

Patient should be consented for laparoscopic as well as open appendectomy. Antibiotics/ Common Organisms

• One dose is adequate for uncomplicated disease. • Metronidazole plus a first-generation cephalosporin, aminoglycoside, or quinolone • Common organisms are Escherichia coli, Bacteroides, Klebsiella, Enterococcus, and Pseudomonas.

INTRAOPERATIVE CARE Choice of Anesthesia

• Laparoscopic appendectomy: – General endotracheal anesthesia (GETA) • Open appendectomy: – GETA – Spinal or epidural anesthesia with a T10 level is also possible.

Monitors

• Standard ASA monitors • Foley, if patient has not voided in the immediate preoperative period, or per surgeon request to improve visualization

Induction/Airway Management

• Sequential compression devices should be placed prior to induction. • Rapid-sequence induction with endotracheal intubation is often required unless a difficult airway is anticipated. If there is a potential for a difficult airway, consider an awake fiberoptic intubation. • Muscle relaxants: The speed of onset of succinylcholine is favorable; however, it may be contraindicated in certain patients (e.g., children, stroke, etc.). Non-depolarizing muscle relaxants administered at induction doses may not be reversible by the end of the case. • Place an orogastric tube after intubation for gastric emptying

Maintenance

• Choice of inhalation agent • Muscle relaxation can enhance surgical exposure. If succinylcholine was used at induction, subsequent non-depolarizing administration may be needed. • If a laparoscopic approach is used, the initial insufflation may lead to bradycardia from vagal stimulation, which should resolve with time. Desufflation may be necessary if the patient becomes hemodynamically unstable. • As with other laparoscopic procedures, the pneumoperitoneum is created to enhance visualization. However, it can impair ventilation by decreasing lung compliance and functional residual capacity. Additionally, the Trendelenburg position is often implemented to displace bowel with gravity and can further impair ventilatory efforts.

Extubation/Emergence

The patient should be fully awake, fully reversed, and capable of protecting their airway to avoid aspiration. Pediatric Considerations

• Appendicitis is more difficult to diagnose in children because of an inability to obtain a good history. Younger children are more likely to present with perforated appendicitis because of this diagnostic challenge. • Surgery may be safely delayed until morning, without undertaking significant risk to the child. • Consider performing an ipsilateral transverse abdominal plane (TAP) block to improve pain control and decrease postoperative narcotic requirements.

FOLLOW-UP No need to continue antibiotics postoperatively for uncomplicated appendicitis BED ACUITY

• Floor bed is typically sufficient. • Telemetry or ICU may sometimes be necessary in the event of a perforated appendix or other comorbid conditions.

ANALGESIA

• Generally mild-to-moderate pain, much improved after appendix removed • Consider IV narcotic +/– ketorolac • Regional techniques include TAP block or a thoracolumbar paravertebral block.

COMPLICATIONS

• Wound infection • Intra-abdominal abscess • Appendiceal stump leak • Thromboembolism • Injury to other structures in the surgical field

REFERENCES

1. Katkhouda N, Mason R, Towfigh S, et al. Laparoscopic vs. open appendectomy: A prospective randomized double-blind study. Ann Surg. 2005;242(3):439–448. 2. McGory M, Zingmond D, Tillou A, et al. Negative appendectomy in pregnant women is associated with a significant risk of fetal loss. J Am Coll Surg. 2007;205(4):534–540. 3. Sauerland S, Jaschinski T, Neugebauer EAM. Laparoscopic versus open surgery for suspected appendicitis. Cochrane Database Syst Rev. 2010;10:CD001546. 4. Surana R, Quinn F, Puri P. Is it necessary to perform appendectomy in the middle of the night in Children? BMJ. 1993;306(6886):1168. See Also (Topic, Algorithm, Electronic Media Element) Laparoscopy

CLINICAL PEARLS

• Appendicitis occurs most commonly in young patients; it has greater morbidity in those over 60 years of age. • In the event of a ruptured appendix, immediate appendectomy is not the management of choice. Antibiotic therapy, fluid resuscitation, and percutaneous drainage should be undertaken with an interval appendectomy performed at a later date after the patient has recovered. • The open and laparoscopic approaches to an appendectomy are both appropriate; patient comorbidities should play some role in the decision-making of the surgeon. • A delay in proceeding to surgery does not affect patient outcome; it is a delay in diagnosis that affects outcome.

ARTERIAL LINE WAVEFORM John C. Frenzel, MD

BASICS DESCRIPTION

• An arterial line is an invasive monitor that provides: – Beat-to-beat numeric blood pressure values – A waveform with arterial pressures (y-axis) as a function of time (x-axis) – A means to attain arterial blood gas sampling • An electromechanical transducer is coupled to the patient via a fluid column that is generally composed of normal saline and heparin (4 units/mL). PHYSIOLOGY PRINCIPLES

• During the cardiac cycle, blood ejected from the left ventricle (LV) flows into the vascular tree. A pressure wave is transmitted through the vessels and temporally leads the flow of blood. – Measurement of pressure occurs at the level of the transducer, not the location of the cannula. This is in contrast to noninvasive blood pressure (NIBP) measurements, where measurement occurs at the level of the cuff. – The arterial waveform is a measure of pressure and does not necessarily correlate to cardiac output (flow). For example, in patients with poor cardiac output and a high systemic vascular resistance (SVR), pressure will be normal but perfusion inadequate. • Anacrotic limb describes the first phase of the arterial pulse cycle and represents ventricular ejection of blood. The highest point corresponds to the systolic blood pressure. – Steep slopes can correspond to increases in HR and inotropy. – Dampened slopes can correspond to decreases in HR and contractility.

FIGURE 1. Arterial line waveform. Point 1 to 2 represents the anacrotic limb. Point 2 to 3 represents the dicrotic limb, with the dicrotic notch found along the way.

• Dicrotic limb describes the downstroke of the waveform; it begins at the peak, continues through the dicrotic notch, and ends at the diastolic baseline. The dicrotic notch coincides with closure of the aortic valve and the end of LV ejection. It is a result of the reflection of

the pressure wave created when the forward flow of blood out of the LV stops and the elastic recoil of the aorta forces blood back against the closed aortic valve. Pressure decay is the drop in pressure over time (dP/dT) from the dicrotic notch to diastolic pressure; it is a function of SVR. – Steep slopes correspond to decreased SVR/afterload. The waveform appears narrow. – Dampened slopes correspond to increased SVR/afterload. The waveform may appear widened. • The highest fidelity of readings and waveform data occurs when utilizing: – The largest diameter catheter that does not obstruct the lumen of the vessel – The shortest length of high pressure (stiff walled) tubing between the transducer and the patient – Tubing that is free of gas bubbles – Tubing that is free of other obstructions such as clotted blood – A catheter that is placed closer to the central vascular tree • Reflection and deflection occur as blood flows through the vasculature. Because the arterial system undergoes constant pressure adjustments as well as has several bends and branches, the flow of blood is turbulent as well as laminar. Turbulent flow results in pressure waves being reflected much like waves in a pool of water are reflected off the concrete side. This results in increased systolic pressures and decreased diastolic pressures in the more distal arteries; the mean pressure is only minimally affected. Alternatively, if the vessels were straight, and had no branches, flow would be laminar and the pressures would not change in the more distal arteries.

FIGURE 2. Arterial line tracing from proximal to distal sites. Systolic pressures increase, diastolic pressures decrease, while mean pressures remain mostly unchanged.

ANATOMY

• Although any artery can be used, the risk of distal thrombosis limits catheter placement to larger vessels with adequate collateralization.

• The radial artery is the most common location for arterial monitoring. • The ulnar artery is more difficult to cannulate because it is deeper at the wrist. It should not be used if the ipsilateral radial artery has been punctured. – Some suggest the use of the Allen Test to assess the adequacy of collateralization of the hand. – Recent studies have called this into question and if there is doubt, vascular ultrasound should be used (1). • Use of the femoral artery must be balanced against concerns of site and line infection, pseudo-aneurysm formation, or distal embolization from plaque rupture. • Other less frequently used sites for arterial wave monitoring include axillary, brachial, and dorsalis pedis vessels. • In neonates temporal and umbilical arteries are used.

DISEASE/PATHOPHYSIOLOGY

• Dicrotic notch: The notch is a result of the reflection of the pressure wave created when the forward flow of blood out of the LV stops and the elastic recoil of the aorta forces blood back against the closed aortic valve. – Patients with severe aortic insufficiency will have an indistinct notch. Since the aortic valve is incompetent, blood flows freely backward, and no such pressure wave is generated. – A flat or absent notch may suggest low intravascular volume. – A low or late notch may correlate to decreased SVR. • Heparin-induced thrombocytopenia (HIT): In some patients, chronic exposure to heparin can result in HIT (2). HIT results in thrombosis, not bleeding. Sodium citrate has been used as a substitute for heparin in the flush (3). • Thrombosis is an unusual complication but potentially devastating if it results in prolonged ischemia (4). First-line therapy is systemic anticoagulation. Some studies have been performed showing thrombolytics are effective as second-line therapy (5). • Temporary occlusion of the radial artery following arterial line placement is not infrequent and is reported in 1.5–35% (mean 19.7%) of studies on the subject. Generally temporary occlusion has no serious consequences (6).

PERIOPERATIVE RELEVANCE

• Placement of arterial waveform monitoring is common when continuous beat-to-beat blood pressure measurement is indicated. Changes in the waveform can be useful in cases where rapid changes in volume status are occurring. • Dampened waveforms result in underestimation of the blood pressure and can be seen with: – Lumen occlusion due to thrombosis, clots, air bubbles, or kinking – Loss of backpressure from the flush solution (low flush bag pressure, no fluid in pressure bag) – Troubleshooting involves inspection of the system starting from the placement site (if possible) back to the electronics. On opening the transducer to air, the reading should drop to zero. If not, this indicates the possibility of baseline drift and the system should be re-zeroed. Next, the system should be flushed. If the reading does not move over 300 mm▒Hg, then the pressure bag should be checked. Otherwise the system should be

inspected distal to the transducer for obstructions, disconnections, or leaks. – Tubing: overly compliant, distensible; incorrect tubing

FIGURE 3. Dampened tracing results in decreased systolic pressures, increased diastolic pressures, while mean pressures remain mostly unchanged.

• Under-dampened or resonant waveforms result in overestimation of the blood pressure and can occur due to: – Tubing: Long, noncompliant, overly-stiff. – “Ringing” describes exaggerated highs and lows that can occur when the measurement system comes close to the natural underlying harmonic frequency of the waveform. – Increased SVR

FIGURE 4. Under-dampened or resonant tracing results in increased systolic pressures, decreased diastolic pressures, while mean pressures remain mostly unchanged.

• The electromechanical system must be zeroed prior to use by opening the transducer to air. For neurosurgical cases, or cases where the patient is in the sitting position, the zero reference is commonly set to the Circle of Willis at the level of the ear. Otherwise, the zero reference is placed at the level of the heart. If the transducer is not physically attached to the OR bed, the level must be adjusted when changes in patient position or vertical height are made. • Stroke volume variation describes changes in the systolic and diastolic pressure that correlate with the respiratory cycle. – Mechanical ventilation: Positive pressure inspiration corresponds with an increase in airway pressures, compression of intrathoracic veins, and a decrease in transmural blood

flow. As a result, with inspiration, there is decreased preload that corresponds to decreased blood pressure. Conversely, exhalation corresponds to a decrease in airway pressures with increases in blood pressure. – Spontaneous ventilation: Exhalation and the end of inspiration correspond to an increase in airway pressures, compression of intrathoracic veins, and a decrease in transmural blood flow.

FIGURE 5. Stroke volume variation with mechanical ventilation. Exhalation corresponds to decreased intrathoracic

pressures, allowing blood to return to the heart (increased preload, with resultant increase in cardiac output and blood pressure). Inspiration corresponds to increased intrathoracic pressures with resultant decreases in blood return to the heart (decreased preload that causes decreases in stroke volume, cardiac output, and blood pressure).

• Arterial line placement can be aided by ultrasound, but this is usually reserved for femoral cannulation of pediatric patients and select adults. • Newer methods of cardiac output monitoring use a peripheral arterial line and the pressure waveform to calculate cardiac output. Unlike thermodilution methods, these devices use advanced algorithms to assess vascular tone and sensing technology to indirectly measure SVR. • Arterial transducers are built to continually infuse a small volume (3 mL/hr) of flush solution to reduce cannula thrombosis.

EQUATIONS

MAP = DBP(2/3) + SBP(1/3); where MAP is mean arterial pressure, DBP is diastolic blood pressure, and SBP is systolic blood pressure. This represents the average, or mean, blood pressure throughout the cardiac cycle.

REFERENCES

1. Jarvis MA, Jarvis CL, Jones PRM, et al. Reliability of Allen’s test in selection of patients for radial artery harvest. Ann Thorac Surg. 2000;70(4):1362–1365. 2. Chong BH. Heparin-induced thrombocytopenia. J Thromb Haemost. 2003;1:1471–1478. 3. Branson PK, McCoy RA, Phillips BA, et al. Efficacy of 1.4 percent sodium citrate in maintaining arterial catheter patency in patients in a medical ICU. Chest. 1993;103:882– 885. 4. Mangano DT, Hickey RF. Ischemic injury following uncomplicated radial artery catheterization. Anesth Analg. 1979;58:55–57. 5. Geschwind JH, Dagli MS, Lambert DL, et al. Thrombolytic therapy in the setting of arterial

line-induced ischemia. J Endovasc Ther. 2003;10:590–594. 6. Scheer BV, Perel A, Pfeiffer UJ. Clinical review: Complications and risk factors of peripheral arterial catheters used for haemodynamic monitoring in anaesthesia and intensive care medicine. Crit Care. 2002;6(3):199–204. See Also (Topic, Algorithm, Electronic Media Element) • Transducers • Hypertension • Heparin-induced thrombocytopenia

CLINICAL PEARLS

• Transducer systems can drift leading to erroneous readings. Leaving a NIBP cuff on the patient and set to cycle every 15 or 30 minutes can help to more rapidly identify this problem. • Placing the pulse oximeter on the same hand as the arterial line can be helpful in monitoring adequacy of perfusion distal to the arterial line. • Check and tighten all connections after placement. Stopcocks that are not used for blood sample draws should be taped in the vertical position and the draw port covered by a cap and tape to avoid inadvertent injection of substances via the arterial line.

ASPIRATION

Kanishka Monis, MD Poovendran Saththasivam, MD

BASICS DESCRIPTION

• Aspiration is defined as the inhalation of gastric, oropharyngeal, or other foreign contents into the larynx and lower respiratory tract. It can be divided into 2 broad categories: – Aspiration pneumonitis: Inhalation of sterile acidic gastric contents resulting in chemical injury to the lung; also known as Mendelson syndrome – Aspiration pneumonia: An infectious, pathologic process caused by inhalation of secretions that have been colonized by microorganisms • Although aspiration is rare during anesthesia, it is an important cause of anesthesia-related mortality and ventilator-associated pneumonia (VAP) in the ICU setting. EPIDEMIOLOGY Incidence

3.1–10.2 per 10,000 patients receiving general anesthesia Morbidity

• Pneumonia • Lung abscess and empyema • Acute lung injury (ALI) • Acute respiratory distress syndrome (ARDS)

Mortality

3.8–4.6%; massive aspiration can reach 25% ETIOLOGY/RISK FACTORS

• Extremes of age • Full stomach at the time of anesthesia • Pregnancy • Critical illness • Emergency surgeries • Gastroesophageal reflux disease • Diabetic gastroparesis • Obesity • Difficult airway • Acidic gastric content pH <2.5 • Gastric volume >0.4 mL/kg • Loss of airway reflexes

– Drug/alcohol overdose – Unconscious patient from general anesthesia, deep sedation, trauma • Neurologic dysphagia

PHYSIOLOGY/PATHOPHYSIOLOGY

• There are several structures and reflexes that protect against aspiration. – Upper esophageal sphincter (UES) The cricopharyngeus muscle acts as the constrictor muscle of the pharynx and divides the upper esophagus from the hypopharynx. Decreased tone is seen with sodium thiopental, succinylcholine, midazolam, and halothane. Increased tone is seen with the use of ketamine. – Lower esophageal sphincter (LES) Located at the border between the stomach and the esophagus Composed of the right crux of the diaphragm and the acute angle of the left margin of the esophagus with the gastric fundus; it forms a sling around the lower esophagus. Decreased tone is seen with opioids, inhalation agents, and sodium thiopental. Increased tone is seen with antiemetics (metoclopramide), cholinergic drugs, and succinylcholine. – Airway reflexes Laryngospasm: Hypoxia results from the closure of the false and true vocal cords; however, this prevents aspiration of foreign contents. Coughing: Forceful expiratory flow can aid with removal of foreign contents. Expiration: Describes a forceful expiratory effort without preceding inspiration Spasmodic panting: Episodes of shallow breathing result in rapid vocal cord opening and closing and reduce the aspiration of foreign material. • Consequences of aspiration – Large particles will cause airway obstruction. Areas of lung that are not being ventilated are still perfused leading to ventilation/perfusion (V/Q) mismatching, shunting, hypoxemia, and death. – In aspiration pneumonitis, acid-related effects of gastric contents will cause inflammatory reactions and direct lung tissue injury, airway constriction, and edema. Release of cytokines and chemokines attract inflammatory mediators, neutrophils, and macrophages. Altered lung defenses may lead to bacterial infection. – In aspiration pneumonia, the aspiration of oropharyngeal secretions and contaminated gastric contents will elicit an acute inflammatory lung response to bacteria and bacterial products. The pathogens that are frequently associated with aspiration pneumonia are Gram-positive cocci, Gram-negative rods, and (rarely) anaerobes.

Pregnancy Considerations

• Pregnant patients in labor have an increased risk of aspiration due to: – Slow gastric emptying time – Increased gastric volume – Relaxation of the LES due to progesterone’s effect and the upward pressure of the enlarging uterus on the LES. Patients are typically considered a “full stomach” beginning

their second trimester.

PREVENTATIVE MEASURES

• Adequate preoperative fasting to control gastric content and volume:

See Table • Decrease gastric acidity: – Sodium citrate is a nonparticulate antacid that functions to raise gastric pH as well as increase gastric motility. – H2 antagonists inhibit secretion of acid, thereby reducing acidity of stomach contents and

gastric volume. • Decrease gastric volume: – Metoclopramide is an antidopaminergic and cholinergic which speeds gastric emptying and increases LES tone. – Nasogastric tube insertion and suctioning prior to or after induction for gastric decompression – In situ nasogastric tubes should be suctioned prior to induction. Of note, it can form a mechanical barrier to LES protection against aspiration. • Application of cricoid pressure/Sellick maneuver: – Described by Sellick in 1961 as a way to prevent aspiration during the rapid sequence induction phase of anesthesia – The upward and backward directed pressure on the cricoid cartilage compresses the esophagus against the vertebral bodies, thus occluding the esophagus. The recommended pressure is 30–40 Newtons (difficult to ascertain while performing the technique). – Theoretically, this will prevent passage of gastric content into the pharynx and subsequent aspiration into the tracheobronchial tree. – Minimizes gastric insufflation and aspiration in unconscious patients; however, it may also prevent effective mask ventilation by reducing airway patency. It may cause discomfort to the patient if applied too early. • Early endotracheal intubation with a cuffed endotracheal tube will decrease but not eliminate the risk of gastric aspiration. – Excessive cuff pressure may compromise the microcirculation of tracheal mucosa leading to necrosis. Insufficient cuff pressure may impair ventilation and allow leakage of supraglottic material into the tracheobronchial tree. – A better seal can be achieved by using the ultra thin cuff (low pressure, high volume). This prevents the formation of folds that can lead to longitudinal channels for supraglottic material to enter the tracheobronchial tree.

Pregnancy Considerations

• Consider all laboring patients as having a "full stomach," irrespective of the last meal time. – Avoid general anesthesia, if possible – If general anesthesia is necessary, consider metoclopramide, sodium citrate, and H2 antagonists. • Semi-recumbent position has been endorsed by the Centers for Disease Control and Prevention (CDC) as an effective measure to decrease the risk of aspiration and VAP.

– Reflux of gastric contents is counterbalanced by the effect of gravity in the semirecumbent position. – Prone position in patients with ARDS has been reported to reduce gastric aspiration and risk of VAP in some studies.

DIAGNOSIS • Vomiting at the time of induction or following extubation • Symptoms: – Postoperative coughing, hoarseness, night sweats, shortness of breath, pleuritic chest pain, myalgia, and malaise • Signs: – Intraoperatively: Hypoxemia, wheezing, bronchospasm/laryngospasm – Postoperatively: Fever, cyanosis, tachypnea, inspiratory wheezing (in lesions where the obstruction is in proximal trachea) or expiratory wheeze (distal obstruction), rales, irritability • Diagnostic tests and imaging: – ABG with an increased alveolar–arterial oxygen gradient and hypoxia – CXR may reveal consolidation and opacities. Changes may be delayed and not appear for 12–24 hours after initial aspiration. – CBC with differential – Sputum culture

DIFFERENTIAL DIAGNOSIS

• Pulmonary thromboembolism • Pulmonary air embolism • Pulmonary tuberculosis • ARDS • Drug reaction • Asthma • Bronchospasm • Laryngospasm • Myocardial infarction

TREATMENT • Vomiting at induction – Immediately place the patient in the Trendelenburg position to prevent aspiration into the trachea – Suction the upper airway – Endotracheal intubation and inflation of the cuff – Endotracheal suctioning with a soft suction tube; bronchoscopy and removal of large inhaled particles • Vomiting intraoperatively (with a supraglottic device or mask ventilation)

– Remove supraglottic device and have an assistant maintain cricoid pressure – Head down/lateral position – Suction and clear the upper airway – Administer 100% oxygen – Administration of succinylcholine and endotracheal intubation for airway protection – Expedite surgery • Vomiting at emergence – Head down or lateral position to prevent the entry of aspirated contents into the airway – Gentle suctioning of the pharynx – Administer 100% oxygen – Consider reintubation for airway protection • There is no data to support the use of steroids in the treatment of aspiration. – Antibiotics should be considered once a specific organism is identified. – In situations that involve bowel obstruction and aspiration of bowel contents, Gramnegative and Gram-positive antibiotic coverage should be considered if the patient develops signs of aspiration pneumonia. • There is no data to support use of steroids in treatment of aspiration pneumonitis or pneumonia.

FOLLOW-UP CLOSED CLAIMS DATA

• In 4,459 total anesthesia-related claims: – Aspiration was the primary or secondary cause of morbidity in 158 (3.5%) of all claims. – Aspiration was the primary source of adverse events in 1.75% of these patients. – The majority of aspiration events (42%) occurred during the induction of anesthesia. – Obstetrical related aspiration accounted for 21% of all claims.

REFERENCES

1. Yoshikawa H, Yamazaki S, Abe T. Acute respiratory distress syndrome in children with severe motor and intellectual disabilities. Brain Dev. 2005;27(6):395–399. 2. Brownlee IA, Aseeri A, Ward C, et al. From gastric aspiration to airway inflammation. Monaldi Arch Chest Dis. 2010;73(2):54–63. 3. Beck-Schimmer B, Bonvini JM. Bronchoaspiration: Incidence, consequences and management. Eur J Anaesthesiol. 2011;28(2):78–84. 4. Paintal HS, Kuschner WG. Aspiration syndromes: 10 clinical pearls every physician should know. Int J Clin Pract. 2007;61(5):846–852. 5. Kluger MT, Visvanathan T, Myburgh JA, et al. Crisis management during anaesthesia: Regurgitation, vomiting, and aspiration. Qual Saf Health Care. 2005;14(3).

ADDITIONAL READING • ASA NPO Guidelines

See Also (Topic, Algorithm, Electronic Media Element) • Ventilator-associated pneumonia • Asthma • Venous air embolism

CODES ICD9

• 482.9 Bacterial pneumonia, unspecified • 507.0 Pneumonitis due to solids and liquids ICD10

• J15.9 Unspecified bacterial pneumonia • J69.0 Pneumonitis due to inhalation of food and vomit

CLINICAL PEARLS

• All patients with stroke should be screened for swallowing abnormalities to prevent aspiration. • Patients with decreased sensorium are unable to protect the airway, thus are at an increased risk for aspiration. • Mechanically ventilated patients with risk factors of aspiration should be nursed by placing the head of the bed elevated at 30–35°.

ASSESSMENT OF ACUTE POSTOPERATIVE PAIN Thomas Ledowski, MD, PD, DEAA, FANZCA

BASICS DESCRIPTION

• Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage” by the International Association for the Study of Pain (ISAP). • It is often referred to as the “fifth vital sign,” and relief from pain is seen as a basic human right. Pain is by its very nature an entirely subjective experience and should always be regarded as such! • Anesthesia providers and pain medicine physicians encounter pain in the acute and chronic setting: – Acute pain is of recent onset and probable limited duration. – Chronic pain commonly persists beyond the time of healing of an injury; frequently there may not be any clearly identifiable cause. EPIDEMIOLOGY Prevalence

• Annually in the US, there are >73 million surgical procedures. An expected 80% of patients experience acute pain with up to 87% of those being moderate and severe. • Following an ICU stay, approximately 75% of patients report to have suffered from moderate-to-severe pain. • Children especially suffer from postoperative pain unnecessarily, with approximately 15% experiencing severe pain. Prevalence

Every day in the US, approximately 175,000 patients suffer from moderate or severe postoperative pain. Morbidity

• Under-treatment of acute pain has significant consequences: – Increased length of hospital stay and rehabilitation leading to high socioeconomic cost – Progression to chronic pain may result in catastrophic personal and socioeconomic consequences. – Triggering of sleep deprivation and anxiety disorders can result in significant personality changes. – Greatly decreased patient satisfaction – Increased overall postsurgical stress response with elevated plasma levels of catabolic hormones, hypercoagulopathy, and increased myocardial oxygen consumption – There is no clear correlation between pain treatment and overall postsurgical mortality

due to a lack of randomized controlled studies. • Over-treatment of acute and chronic pain also has undesired consequences: – Respiratory depression with subsequent hypoxia that can lead to brain damage or death may result from the inappropriate use of opioids; increased occurrence in high-risk patients (e.g., sleep apnea, elderly). – Other adverse events with opioid treatment include constipation, itching, nausea, and vomiting. – Adverse events with NSAIDs include GI ulceration and bleeding.

ETIOLOGY/RISK FACTORS

• Acute postoperative pain depends on the degree of surgical tissue trauma, but is also affected by individual patient factors such as: – Previous experiences – Personality, anxiety, catastrophizing, neuroticism, depression – Cultural background • Risk factors for misdiagnosis of pain: – Inability to communicate verbally (e.g., young children, patients with dementia or delirium, and sedated patients in the ICU) – Medical myths (e.g., infants do not feel pain as much as adults) – Using “objective” physiologic parameters (heart rate, blood pressure) to assess the severity of pain and make treatment decisions; pain is SUBJECTIVE!

PHYSIOLOGY/PATHOPHYSIOLOGY

Adverse physiologic effects in patients with postoperative pain include: • Pulmonary system: Atelectasis, V/Q mismatching, hypoxemia, hypercapnia • Cardiovascular system: Hypertension, tachycardia, increased myocardial oxygen demand • Hematologic system: Decreased immune function, hypercoagulable state • GI system: Ileus PREVENTATIVE MEASURES

• The assessment of pain should be a holistic approach involving patient self-rating, whenever possible. It should also include obtaining a thorough medical and pain history, behavioral observation and, with caution, monitoring of physiologic parameters (e.g., blood pressure, respiration rate). • Pain assessment and treatment by a dedicated acute pain service may result in better pain relief and less side effects.

PREOPERATIVE ASSESSMENT • An initial assessment of postoperative pain must commence as early as possible and consists of a medical (type of surgery, comorbidities) and pain history: – Location – Quality; dull visceral, stabbing, shooting, or neuropathic pain – Intensity – Provoking factors (coughing) versus continuous pain

– Chronic pain history; especially which medications have been used – Factors influencing pain treatment; patient’s beliefs and expectations, knowledge, coping strategies • Reassessment should be repeated regularly at appropriate intervals (e.g., recovery room every 3–5 minutes, ward every 0.5–4 hours). • Physiologic parameters can be used as indicators of pain and include heart rate, blood pressure, and respiration rate. – Although physiologic parameters are often used as a “crutch” to assess pain in unconscious patients, they should only be used with extreme caution to guide therapeutic decisions. None of them have been validated as accurate measures of pain! • A variety of pain scales are available. They range from scales “objectively” measuring pain in conscious patients to scales used in unconscious and pediatric patients. • Verbal descriptor scale (VDS): Conscious patients. Pain is described as absent, mild, moderate, severe, and agonizing/unbearable. – Quick and easy – Useful in elderly patients with cognitive impairment; use familiar words such as no, mild, moderate, unbearable (2)[C] – Less sensitive to pain changes and dependent on higher verbal skills (e.g., a patient who barely speaks English may not understand the term “agonizing”) • Visual analogue scale (VAS): Conscious patients. Consists of a 100 mm long horizontal line with the words “no pain” on the left (0) and “worst pain imaginable” on the right (100). The patient marks his/her actual severity of pain on the scale (pen/paper or ruler/sliding marker system). – Helpful in most conscious subjects – A reduction of pain by approximately 30% has been rated meaningful by patients. – Clinical use may be hindered by anesthesia-related cognitive impairment in the immediate postoperative period. – Requires basic motor skills; 0–5 mm commonly signify “no”, 5–45 mm “mild”, 45–74 mm “moderate” and 75–100 mm “severe” pain • Numeric rating scale (NRS): Conscious patients. Commonly 0–10 points, hence an 11-point scale. 0 means no pain, 10 worst pain imaginable; 4 is often used as the threshold for treatment intervention (e.g., opioid administration). – The NRS correlates well with the VAS but is easier to administer with consistent results. • Multidimensional pain scales (e.g., McGill Pain Questionnaire); conscious patients – Helpful to evaluate more complex pain issues (e.g., chronic or neuropathic pain) – Due to their complexity, these pain scales are usually not useful in the acute postoperative context. • Functional pain scales: Conscious patients. Assesses a patient’s ability to perform certain tasks (e.g., coughing, physiotherapy). Commonly rated as “no” (performance unhindered by pain), “mild” (moderate-to-severe pain during task), and “significant” limitation (unable to perform task). – The ability to perform a certain task may be influenced by more factors than just pain, but such scales can be useful to trigger pain therapeutic intervention. • Behavioral pain scale (BPS): Sedated or semi-conscious patients. 3 components are analyzed:

Facial expression (relaxed, partially tightened, fully tightened, grimacing), upper limb movement (none, partially bent, fully bent, permanently retracted), and compliance with ventilation (tolerant, mostly tolerant, fighting ventilator, unable to control ventilation). Each component is rated from 1 to 4; hence, a total BPS score of 12 (maximum pain) can be achieved. – BPS is reliable and valid for pain assessment in sedated adult ICU patients (3)[B]. • Critical care pain observation tool (CPOT): Sedated or semi-conscious patients. 4 domains: Facial expression (relaxed, tense, grimacing), body movement (none, protective, restless), muscle tension (relaxed, tense, rigid), compliance with ventilation (tolerant, coughing, fighting), or, in extubated patients, vocalization (normal, moaning, crying); rated from 0 to 2 points each. CPOT ranges from 0 to 8 (maximum pain). – The CPOT correlates with the VAS which supports its clinical use (4)[C]. • Premature infant pain profile (PIPP) has been validated for postoperative pain in both premature infants and term newborns. Indicators: Gestational age, behavioral state, heart rate, oxygen saturation, brow bulge, eye squeeze, nasolabial furrow; all marked with 0–4 points with a total score of 0–21 points (moderate-to-severe pain if >12). • Children’s Revised Impact of Event Scale (CRIES). Indicators: Crying, oxygen requirement, increased heart rate and blood pressure, expression, sleeplessness; all marked 0–2 points, total score 0–10. • Faces Legs Activity Cry Consolability Scale (FLACC). Indicators (1–3 year olds): Facial expression, leg movement, overall activity, crying, consolability; each factor scores 0–2 points, with a total score of 0–10 points. • Faces Pain Scale-Revised (FPS-R). Indicators (4–7 year olds): Showing 6 faces (very happy to very sad/crying); shown to be equivalent to a 5-step scale graded 0–10 VAS on paper/ruler.

DIFFERENTIAL DIAGNOSIS

• When solely based on clinical observation and the monitoring of physiologic parameters, pain assessment may be confounded by a range of other factors including: – Arousal (potent sympathetic stimulus) – Anxiety (especially children) – Confusion (especially elderly patients, emergence delirium in children) – Co-medication (antihypertensive drugs, sympatholytic [e.g., beta-blockers, clonidine] and sympathomimetic drugs [e.g., catecholamines, ketamine]) • Hence, get a patient self-rating whenever possible.

TREATMENT Consists of a multimodal approach including: • Oral and parenteral analgesics (opioids, NSAIDs, acetaminophen) • Patient-controlled analgesia (PCA) • Regional and neuraxial blocks • Non-conventional therapies (e.g., transcutaneous electrical nerve stimulation)

FOLLOW-UP In-hospital postoperative patients may have their pain managed by either the surgical team, primary service, anesthesia service, or acute pain team. CLOSED CLAIMS DATA

• From 1985 to 2007, there were 150 out of 7,328 closed claims related to acute pain (American Society of Anesthesiologists Closed Claims Project). – Although this may appear to be a low percentage, the outcome in approximately 30% of cases was death or brain damage. – The median payment was $211,650 ($627–14,880,000). • Pain mismanagement has been viewed as “unprofessional conduct” by state medical boards with individual doctors being disciplined.

REFERENCES

1. esonen A, Kauppila T, Tarkkila P, et al. Evaluation of easily applicable pain measurement tools for the assessment of pain in demented patients. Acta Anaesthesiol Scand. 2009;53:657–664. 2. Pesonen A, Suojaranta-Ylinen R, Tarkkila P, et al. Applicability of tools to assess pain in elderly patients after cardiac surgery. Acta Anaesthesiol Scand. 2008;52:267–273. 3. ade CH. Clinical tools for the assessment of pain in sedated critically ill adults. Nurse Crit Care. 2008;13:288–297. 4. Tousignant-Laflamme Y, Bourgault P, Gelinas C, et al. Assessing pain behaviours in healthy subjects using the critical care pain observation tool (CPOT): A pilot study. J Pain. 2010;11:983–987.

ADDITIONAL READING

• Macintyre PE, Scott DA, Schug SA, et al. Acute pain management: Scientific evidence, 3rd ed. Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine, 2010.

See Also (Topic, Algorithm, Electronic Media Element) • Complex regional pain syndrome I • Complex regional pain syndrome II • Epidural

CODES ICD9 338.18 Other acute postoperative pain ICD10

G89.18 Other acute postprocedural pain

CLINICAL PEARLS

• Pain is a SUBJECTIVE experience. • Pain is often misdiagnosed in young children, as well as demented and sedated patients. • Pediatric pain scales should be age-adequate; there is no “one-fits-all” scale. • Physiologic parameters as well as newly introduced monitoring solutions (e.g., skin conductance or surgical pleth index) are influenced by many factors other than pain; if used, they require caution and support from other methods of pain assessment (e.g., observation). • The adequacy of pain relief should be checked regularly. • Assessment alone is not enough. Clear orders and policies must also define which level of pain triggers and which response/medication to alleviate it.

ASSIST CONTROL VENTILATION Daniel Castillo, MD Sascha Beutler, MD, PhD

BASICS DESCRIPTION

• Assist control ventilation (A/C) or assisted mechanical ventilation (AMV) is a full support mode of mechanical ventilation that is used preferentially across the intensive care units (ICU) in the US and around the world (1)[B]. Spontaneous breathing modes have been shown to decrease atelectasis and can improve V/Q matching. • In this mode, the breath can be triggered by the set rate (ventilator-triggered) or by the patient; the “interactive” element of this mode allows the patient to receive a “fully supported” breath when they initiate one. • Patients ventilated with A/C can go from total ventilatory rate control when apneic, sedated, or paralyzed to full patient trigger rate control when spontaneously breathing (2) [B],(3)[B]; this change will occur seamlessly without changing the ventilator settings. • In A/C, as in other modes of ventilation, it is necessary to set parameters such as: – FIO2 – Positive end expiratory pressure (PEEP) – Pressure-targeted or volume-targeted – Respiratory rate – Mode of triggering: Negative pressure- triggering or flow-triggering – Peak flow

PHYSIOLOGY PRINCIPLES

• Mechanical ventilation (MV) parameters: MV is based on the equation of motion, where pressure, volume, and flow change continuously during the respiratory cycle, assuming that compliance and resistance remain constant (4)[A]. • Physiologic ventilatory control: The respiratory center in the brain stem controls ventilation. Signals are delivered to the respiratory muscles to contract and create a negative intrapleural pressure, resulting in lung expansion and airflow entering the airways. • Interactive components of AC ventilation: During MV, if the patient initiates a breath, the ventilator is triggered to deliver a preset breath to the patient. • Backup rate: When the patient is unable to initiate a breath, the set ventilatory rate delivers the breaths. This functions as a backup or “safety-net” when the patient’s breathing rate drops below the ventilator set rate (5)[C],(6)[B],(7)[B],(8)[B]. • Patient-triggered versus ventilator-triggered breaths: The delivered breath in A/C is equally supported regardless if it is patient or ventilator initiated; they are identical in duration and magnitude. • Work of breathing: Contrary to popular belief, A/C does not abolish the work of breathing because breaths remain initiated by the patient; it does, however, decrease it. As a result,

there is decreased fatigue and shallow breaths that can result in atelectasis and shunting. • Settings: – FIO2: As with most modes of ventilation, this needs to be selected. Patients are often started at an FIO2 of 1.0 with downward titration to avoid oxygen toxicity and decreased

surfactant production. – PEEP: Reduces atelectasis during expiration with resultant improvement in oxygenation, lung volumes (by increasing FRC), and lung compliance. PEEP also antagonizes autoPEEP. In acute respiratory distress syndrome (ARDS), it can decrease atelectrauma (the opening and closing of airways) and the effects of volutrauma. Initially, PEEP is typically set at the lower inflection point (LIP) of a pressure-volume curve and then titrated upwards to produce the best PaO2 with an FIO2 <0.6.

– Method of support (tidal volume vs. pressure targeted): In tidal volume support, a volume is set for each breath. The volume set is delivered using a fixed flow (flow × time). Airway pressure is not set and will depend on the elastic and resistance component of the lung. Inspiratory time is determined by the VT delivered and the flow rate: Ti = VT/flow rate. In pressure-targeted support, the ventilator utilizes flow (adjustable) to generate a set pressure in the airway for a period of time determined by the inspiratory time of the I:E (inspiration:expiration) ratio. The pressure generated is the same for patient- and ventilator-initiated breaths. The VT generated is not fixed and will depend on the elastic

and resistance components of the lung. For ARDS patients, the goal is to attain a tidal volume of 5–7 mL/kg with peak pressures <30 mm Hg. – Respiratory rate: Some machines set a minute volume that determines the respiratory rate: MV/VT.

– Mode of triggering: Negative pressure sensors are typically found on anesthesia machines and are set at –2 cm H2O. However, because they place an unnecessary workload on

breathing, they have been replaced by flow triggers on ICU ventilators. Flow triggers implement a continuous flow of gas and when patient-triggered inspiration (negative pressure) deflects this flow, the ventilator is triggered. If the trigger is too sensitive, the patient can hyperventilate. If it is not sensitive enough, the patient becomes dyssynchronous. – Peak flow is measured as liters per minute (L/min) and is typically set at 4 times the minute ventilation; this parameter is utilized as opposed to an I:E ratio. In adults, 50 L/min is initially chosen; higher levels may be selected in patients with airflow obstruction. If the flow rate is too high, the volume is rapidly delivered to the most compliant lung tissues (not to the inelastic diseased tissues) at very high peak pressures. If the peak flow is too low, the patient will demand more gas than the ventilator is setup to supply and dyssynchrony with the machine occurs; this is referred to as “air hunger.” Pressure augmentation allows the ventilator to sense that the patient’s demands exceed the peak flow, and automatically increases the flow. • Ventilatory settings are adjusted based upon the patient’s plateau pressure, inspiratory flow demand, and blood gas targets.

ANATOMY

• The airway tree starts with the trachea and divides approximately 23 times (dichotomous divisions) to form alveolar sacs that contain 17 alveoli in average. • The average adult has a gas exchange surfaces in the lungs of about 50–100 m2 (300 million alveoli).

PHYSIOLOGY/PATHOPHYSIOLOGY

• Respiratory failure: Respiratory rate >35 breaths/min or <6 breaths/min; oxygen saturation <90% despite adequate supplemental oxygen; tidal volume <5 mL/kg; vital capacity <15 mL/kg; pH <7.20; PaCO2 >50 mm Hg; A-a gradient >350 mm Hg on an FIO2 1.0

• Pulmonary consequences and ventilator-associated lung injury – Barotrauma can be seen with excessive pressures and can lead to pneumothorax, pneumomediastinum, subcutaneous emphysema, and pneumopericardium. – Volutrauma can be seen with high-end inspiratory volumes that can lead to alveolar stress injury and increased lung water; can be reversed by PEEP. – Atelectrauma; decreases in surfactant result in less “patent” alveoli, or alveolar collapse. The repeated opening and collapsing results in shear stress to the alveoli. – Biotrauma describes the maladaptive inflammatory release that occurs secondary to mechanical factors or biophysical injury. Cytokines, complement, prostanoids, leukotrienes, proteases, and reactive oxygen species can result in damage to distal organs. Tissue injury can result from these inflammatory mediators as well as impaired oxygen delivery and bacteremia. – Hyperventilation and significant respiratory alkalosis can develop, particularly with CNS disorders, febrile states, or sepsis. An alarm can be set if the ventilator cycles too frequently. – Air trapping and breath stacking can occur with obstructive airway disease or with increased respiratory rates (not enough time to exhale the full tidal volume). – Muscle atrophy resulting from disuse develops if used for long, thus the need for gradual weaning of pressure or volume support before extubation. • Cardiovascular effects: Increased intrathoracic pressure – Decreases venous return to the right atrium (preload) and can potentially decrease cardiac output. This can be significant in patients that are hypovolemic, have low ejection fractions, or are preload-dependent (pericardial tamponade). – Can decrease left ventricular afterload by increasing the transmural pressure (less negative). In patients with LV dysfunction, the negative inspiratory pressures that are needed to maintain adequate inspiratory volumes are greater (due to pulmonary edema, the lung volume and compliance decrease). Positive pressure ventilation functions on the principle of increasing intrathoracic pressures and hence makes the transmural pressure less negative. • Renal function has been shown to decrease with positive pressure ventilation (decreased urine output and sodium excretion). • Hepatic function may be affected due to decreased cardiac output, increased hepatic vascular resistance, and elevated bile duct pressure. PERIOPERATIVE RELEVANCE

• A/C is useful for rapid weaning at the end of a case where the patient is not yet breathing spontaneously but expected to shortly (muscle relaxant reversal, decreasing volatile or IV anesthetic levels). Patients can be extubated directly from A/C or switched to pressure support prior to extubation. • In patients not breathing spontaneously (neuromuscular blockade, opioids), there is no difference in minute ventilation between SIMV, AC, or CMV.

EQUATIONS

Equation of motion of the airway: P = VT/C + R × F (P = transpulmonary pressure, VT =

tidal volume, C = compliance, R = resistance, F = flow) (3)[A]

Volume-targeted assist control ventilation. On the left, the patient is receiving controlled, set breaths at a rate of 12/min. On the right, the patient is receiving assisted breaths as can be seen by the small downward deflection produced by a patient-triggered breath. All breaths have an identical tidal volume.

Pressure-targeted assist control ventilation. On the left side, the peak flow is set at 30 L/min, and the scooped out appearance of the pressure trace indicates that the patient is slightly dyssynchronous. On the right side, pressure

augmentation has been added and increases the peak flow rate in response to the patient’s demand. Results in improved dynamics in regard to the pressure and flow waveforms and resembles pressure support, rather than assist control.

REFERENCES

1. steban A, Anzueto A, Alia I, et al. How is mechanical ventilation employed in the intensive care unit? Am J Respir Crit Care Med. 2000;161(5):1450–1458. 2. hiumello D, Pelosi P, Calvi E, et al. Different modes of assisted ventilation in patients with acute respiratory failure. Eur Respir J. 2002;20:925–933. 3. Tejeda M, Boix JH, Alvarez F, et al. Comparison of pressure support ventilation and assistcontrol ventilation in the treatment of respiratory failure. Chest. 1997;111:1322–1325. 4. Nikischin W, Gerhardt T, Everett R, et al. A new method to analyze lung compliance when pressure–volume relationship is nonlinear. Am J Respir Crit Care Med. 1998;158:1052– 1060. 5. Sassoon CSH, Zhu E, Caiozzo VJ. Assist-control mechanical ventilation attenuates ventilator-induced diaphragmatic dysfunction. Am J Respir Crit Care Med. 2004;170(6):626–632. 6. Tobin MJ, Jubran A, Laghi F. Patient–ventilator interaction. Am J Respir Crit Care Med. 2001;163:1059–1063. 7. Tobin MJ. Mechanical ventilation N Engl J Med. 1994;330:1056–1061. 8. Toublanc B, Rose D, Glerant JC, et al. Assist-control ventilation vs. low levels of pressure support ventilation on sleep quality in intubated ICU patients. Intensive Care Med. 2007;33(7):1148–1154. See Also (Topic, Algorithm, Electronic Media Element)

• Continuous positive airway pressure • Positive end expiratory pressure • Acute respiratory distress syndrome • Intubation and extubation criteria

CLINICAL PEARLS

• A/C does not abolish the work of breathing; it can reduce it. • It provides a seamless transition from ventilator-controlled respiration to ventilatorsupported, patient-initiated breaths.

ASTHMA

Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Asthma describes bronchial hyper-reactivity with reversible airflow obstruction in response to various stimuli. Despite its reversible nature, chronic airway inflammation is a hallmark. • A reactive airway, or bronchial hyper-responsiveness, is also seen in chronic bronchitis, emphysema, allergic rhinitis, and respiratory infections. EPIDEMIOLOGY Prevalence

7% of US population, increasing yearly Prevalence

• 1/2 of all cases develop before the age of 10 years • 1/3rd occur after the age of 40 years • 2:1 male:female preponderance up to the age of 30 years, then equalizes

Morbidity

• Perioperative occurrence is seen in 0.17–2.4% of asthmatics. • 40,000 missed school or work days each day • 30,000 asthma attacks daily • 5,000 ER visits daily • 1,000 hospital admissions daily

Mortality

5000/year

ETIOLOGY/RISK FACTORS

• Allergens • Pharmacologic agents (aspirin, beta-blockers, NSAIDS, sulfa) • Infections (viral airway infections increase airway resistance even in non-asthmatics, possibly due to a cholinergic mechanism in the bronchial smooth muscles) • Exercise (post-exercise) • Emotional stress • Cold weather • Abnormal autonomic nervous system regulation • Endotracheal tube, mucus, saliva (anesthetic related) • Pregnant patients administered prostaglandins for abortion or operative delivery

PHYSIOLOGY/PATHOPHYSIOLOGY

• The above-mentioned triggers can elicit bronchial smooth muscle contraction. Additionally, vagal and sympathetic factors directly modulate airway tone (1,2,3). • Acutely, inflammatory edema and mucus plugging exacerbate airflow limitation. Chronically, airway remodeling, thickening, and abnormal communications occur in the epithelium of the injured airway and in the pulmonary mesenchyma; changes are permanent and can result in progressive damage (1,2,3). • Immunologic–inflammatory pathways involve lymphocytes, eosinophils, neutrophils, mast cells, leukotrienes, and cytokines (1,2,3). • Bronchoconstriction increases (3): – Work of breathing – Air trapping – V/Q mismatch (reduced ventilation that causes shunting) – Pulmonary vascular resistance (PVR) – Right ventricle afterload – Residual volume (RV) – Functional residual capacity (FRC) – Total lung capacity (TLC) – Oxygen consumption – Carbon dioxide production • Bronchoconstriction decreases: – Airflow – FEV1 – Expiratory reserve volume (ERV) – Inspiratory reserve volume (IRV) – FEV1/FVC – FEV25-75%

– Dynamic compliance of lungs • Accessory muscles are recruited to preserve tidal volume (TV) despite increased ERV (from increased FRC and air trapping) (1,2). • Initially, hyperventilation causes respiratory alkalosis. Over time, increased air trapping and respiratory muscle fatigue increase CO2 retention; therefore, normalization of PaCO2 reflects decompensation. Extreme air trapping can restrict cardiac filling and “pulmonary tamponade” that can result in pulse-less electrical activity.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess severity of disease, optimize pulmonary function, and treat acute exacerbation • The anesthetic plan should prevent, suppress, and blunt airway hyper-reactivity; stimuli that do not ordinarily evoke airway responses can precipitate life-threatening bronchoconstriction in the asthmatic. • Diagnose and treat perioperative bronchoconstriction

PREOPERATIVE ASSESSMENT

SYMPTOMS

• Shortness of breath • Chest tightness • Cough

History

• Age of onset • Triggers • Treatment history – Frequency of exacerbations – Nighttime awakenings – Rescue inhaler use – Steroids pulse dose – ER visits – Hospitalizations – ICU admissions – Intubations Signs/Physical Exam

• Expiratory wheezing • Accessory muscle use • Tachypnea • Diminished or inaudible breath sounds

MEDICATIONS

• “Controller” to modify airway environment – Inhaled steroids – Theophylline – Leukotriene modifiers – Cromolyn • “Rescue” for acute bronchospasm (quick onset) – Beta-adrenergic agonists – Anticholinergics DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Pulmonary function tests can aid with diagnosis, and objectively assess severity and response to treatment (FEV, FEV1/FVC) • CXR (hyperventilation, pneumonia, CHF) • EKG (acute right heart failure, PVCs) • Eosinophilia • ABGs (pCO2 and pO2) CONCOMITANT ORGAN DYSFUNCTION

77% have gastroesophageal reflux disease (GERD); control of GERD may improve asthma symptoms. CIRCUMSTANCES TO DELAY/ CONDITIONS • Acute exacerbation • Chronic sinus infection • Upper respiratory infection • Pneumonia

CLASSIFICATIONS

• Based on symptoms, nighttime awakenings, short-acting beta-agonist symptoms, interference with normal activity, lung function, oral steroid use – Mild – Moderate – Marked – Severe/status asthmaticus

TREATMENT PREOPERATIVE PREPARATION Premedications

• Consider beta-agonists (MDI, nebulizer) • Consider a steroid stress dose (avoid Addisonian crisis if recent therapy and major surgery) • Consider a steroid pulse dose (avoid perioperative exacerbation in severe disease, or major surgery) • Anxiolysis

INTRAOPERATIVE CARE Choice of Anesthesia

• Consider regional anesthesia to avoid airway instrumentation and stage II emergence (increased risk for bronchoconstriction) • Consider LMA, which sits supraglottically and is associated with less airway irritation than ETT Monitors

• Standard ASA monitors • Consider augmenting the ETCO2 waveform to improve detection of obstruction; a slow rise to the peak indicates expiratory obstruction. • Consider an arterial line in high-risk patients to allow for ABG monitoring

Induction/Airway Management

• Laryngoscopy, intubation, suctioning, and cold inspired gases can exacerbate hyperreactivity.

• Patient should be “deep” prior to airway instrumentation. Ensure that an adequate dosage of induction medications and neuromuscular blockade have been administered, as well as an appropriate amount of time for onset. Induction medications should be titrated to blunt bronchial smooth muscle responsiveness, and NMBD should be titrated to block coughing, gagging, or bucking. Although these are skeletal muscle phenomenon, when provoked, they can precipitate irritant receptors and airway hyper-reactivity. • Consider bag mask ventilating with volatile agents (potent bronchodilators) for 2–3 minutes prior to airway instrumentation • Ketamine is the only bronchodilating IV induction agent; propofol and etomidate blunt airway reflexes to a greater extent than thiopental. • Lidocaine blunts airway response to irritation. However, caution is advised when topically applied; spraying can cause irritation and precipitate bronchospasm. • Succinylcholine has histamine release; however, studies have not shown this to be clinically relevant. • When considering a RSI, the risk of aspiration needs to be weighed against the risk of bronchoconstriction from airway manipulation prior to the patient being “deep.”

Maintenance

• Keep the patient “deep” or adequately anesthetized. Otherwise, innocuous stimuli can result in increased airway resistance (saliva, mucus, ETT). • I:E ratio should be reduced (increased time for exhalation to avoid air trapping; similar to phenomenon of “pursed lip breathing” in patients with emphysema). • Humidify, warm inspiratory gases • Fluid hydration to soften mucus secretions

Extubation/Emergence

• Consider “deep” extubation (removing airway while anesthetic is sufficient to suppress hyper-reactivity) • When it is unwise to extubate before the patient is fully awake, consider suppressing airway reflexes (IV lidocaine, bronchodilators, epinephrine IV/SQ, dexmedetomidine). • Neostigmine may bronchoconstrict if not administered with adequate antimuscarinics. • Antimuscarinics can thicken secretions.

FOLLOW-UP BED ACUITY

• Vigilance for bronchospasm • Consider supplemental oxygen (nasal cannula, face mask) • Consider scheduled bronchodilator treatments • Incentive spirometry and deep breathing • Early mobilization • Good pain control • Control GERD

COMPLICATIONS

• Intraoperative bronchospasm is diagnosed by: – Increased peak inspiratory pressures (PIP) – ETCO2 sloping

– Expiratory wheezing • Treatment consists of: – Deepening the anesthetic with inhaled volatile agents. Volatile agents are potent bronchodilators and cause direct bronchial smooth muscle cell dilation by altering intracellular calcium regulation. However, if there is little or no airway movement, this may not be effective. – Deepening the anesthetic with intravenous agents. Propofol does not bronchodilate, but it can suppress airway reflexes. – Inhaled beta-agonists. Albuterol causes bronchodilation, but may require several puffs (8– 10) to ensure delivery through a long narrow ETT. There are several devices available that can facilitate delivery. – Steroids intravenously. Administration should not preclude more immediate therapy. – Epinephrine (IV bolus, SQ, drip); sympathomimetic that decreases bronchospasm via beta2 agonist. – Theophylline may be considered; however, it is more common for symptom control and prevention. Additionally, it has a narrow therapeutic index and levels need to be monitored if continued postoperatively. – Heliox can promote laminar airflow, but reduces FIO2, and has not been shown to be therapeutic. – Magnesium (drowsiness and NMBD potentiation) – Avoid histamine-releasing medications (e.g. morphine, vancomycin)

REFERENCES

1. Woods BD, Sladen RN. Perioperative considerations for the patient with asthma and bronchospasm. Br J Anaesth. 2009;103(S1):i57–i65. 2. Fanta CH. Asthma. N Engl J Med. 2009;360:1002–1014. 3. Tirumalasetty J, Grammer LC. Asthma, surgery, and general anesthesia: A review. J Asthma. 2006;43(4):251–254.

ADDITIONAL READING

• Asthma and Allergy Foundation of America • Burburan SM, Xisto DG, Ferreira HC, et al. Lung mechanisms and histology during sevoflurane anesthesia in a model of chronic allergic asthma. Anesth Analg. 2007;104(3):631–637. • Overview of Changes to Asthma Guidelines. www.aafp.org See Also (Topic, Algorithm, Electronic Media Element) • Ventilation perfusion matching • Ventilation perfusion mismatching

• Pulmonary function tests • Functional residual capacity • End tidal CO2 • I:E ratio • Deep extubation • Laminar flow

CODES ICD9

• 493.90 Asthma,unspecified type, unspecified • 493.92 Asthma, unspecified type, with (acute) exacerbation ICD10 • J45.901 Unspecified asthma with (acute) exacerbation • J45.909 Unspecified asthma, uncomplicated

CLINICAL PEARLS

• Assess the severity of disease in order to plan an appropriate anesthetic technique. • Stimuli that do not ordinarily evoke airway responses can precipitate life-threatening bronchoconstriction in asthmatics. Ensure that the patient is adequately induced prior to airway manipulation, as well as remains adequately anesthetized during the surgery; consider a “deep" extubation. • Intraoperative bronchoconstriction presents as increased PIP, a sloping ETCO2 waveform, and wheezing. • All that wheezes is not asthma; rule out other causes prior to treating for bronchospasm. • Asthma increases the risk of bronchospasm, hypoxemia, hypercapnia, inadequate cough, atelectasis, and pulmonary infection following surgery.

ATELECTASIS

Arun Alagappan, MD Stephen P. Winikoff, MD

BASICS DESCRIPTION

• Atelectasis refers to a collapse of lung tissue from compression, absorption, or loss of surfactant; it is very common in the perioperative setting. • Atelectasis from anesthesia: – Occurs with both inhalational and intravenous anesthetics – Appears within minutes after induction (1) – Occurs with spontaneous and mechanical ventilation – Primarily affects lung tissue in the basal regions adjacent to the diaphragm – Can be worsened with positioning (supine and Trendelenburg) – Can persist for days after major surgery

EPIDEMIOLOGY Prevalence

• Atelectasis is found in 90% of anesthetized patients (2). • Infants are at a greater risk secondary to their decreased lung compliance relative to their chest wall. Additionally, their closing volume is greater due to incomplete development of the elastic supporting structures of the lung, and as a result, they are at risk for airway closure during tidal volume breathing (2). • Atelectasis is most common after cardiac surgery with CPB (3).

Prevalence

• Observed in all age groups • Magnitude is independent of age in adults (2).

Morbidity

Hypoxemia, right ventricular dysfunction, lung injury Mortality

Pulmonary complications account for 24% of deaths within 6 days of surgery (2). Atelectasis causes physiologic impairments that contribute to the development of these pulmonary complications. ETIOLOGY/RISK FACTORS

• There are 3 mechanisms by which atelectasis can develop: – Compression – Absorption

– Loss of surfactant • Compression atelectasis: Occurs when the transmural pressure that distends the alveolus is reduced. During anesthesia, the diaphragm is relaxed and is cephaledly displaced making it less effective at maintaining distinct pressures in the extrathoracic and abdominal cavities. Abdominal pressures are transmitted to the pleural space and promote collapse of adjacent lung units (3). • Absorption atelectasis: Occurs when less gas enters the alveolus than is removed by uptake of blood. This can happen when there is complete airway occlusion creating a pocket of trapped gas in a distal lung unit that continues to be perfused. Gas uptake from the pocket continues without inflow of gas, and the pocket collapses. Alternately, in the absence of complete airway occlusion, if the VA/Q is reduced, there is a point reached at which the rate of inspired gas entering the alveolus is balanced by gas uptake from the alveolus. Below this critical ratio, the lung unit will collapse. This becomes more likely with increasing FIO2

(2). May be seen when nitrous oxide is changed to 100% oxygen at the end of a case. • Loss-of-surfactant atelectasis: Occurs when the alveolar-stabilizing function of surfactant is depressed by anesthesia or by a lack of intermittent deep breaths. Surfactant is a surfaceactive lipoprotein that is produced by alveolar type 2 cells and acts to reduce alveolar surface tension. The surface tension of the alveolar air–water interface provides a retractive force opposing lung inflation. The presence of surfactant can lower the air–water surface tension to near zero, ensuring that the alveolar space remains open. Abnormalities in the amount or composition of surfactant are seen in certain conditions including neonatal respiratory distress syndrome and acute respiratory distress syndrome (ARDS), as well as secondarily from inflammatory processes in the lung (4). • Other contributing factors to atelectasis under general anesthesia include: – Obesity: The weight of the chest wall and abdomen makes diaphragmatic excursion more difficult and promotes atelectasis (5). Studies have shown that atelectasis resolves more slowly compared to nonobese patients. – Positioning: In the supine position, abdominal contents have cephalad invasion against the relaxed diaphragm. In Trendelenburg, gravity further accentuates this. – Laparoscopy: Pneumoperitoneum promotes atelectasis. Studies have also shown that it is associated with an increased incidence of postoperative atelectasis (5).

PHYSIOLOGY/PATHOPHYSIOLOGY

• Atelectasis causes several physiologic impairments in respiratory function resulting in a range of clinical findings including: – Hypoxemia – Decreased pulmonary compliance – Right ventricular dysfunction – Worsening of lung injury • Hypoxemia results from ventilation perfusion mismatching or shunt. Perfusion to the alveolar unit continues despite the lack of ventilation. • Decreased pulmonary compliance is primarily through a reduction in lung volume (3). This increases the work of breathing by requiring an increased transpulmonary pressure to achieve a given tidal volume.

• Right ventricular dysfunction: Atelectasis contributes to regional hypoxia that in turn contributes to hypoxic pulmonary vasoconstriction and increased pulmonary vascular resistance. This can result in right ventricular dysfunction and increased microvesicular leakage (3). • Lung injury: Atelectasis can potentiate existing lung injury in both high and low tidal volume ventilation strategies. In high tidal volume ventilation with zero PEEP, atelectasis causes increased serum cytokine concentrations as well as impaired lung compliance (3). During low tidal volume ventilation in the presence of atelectasis, there was shown to be a decrease in survival (3). • Chronic obstructive pulmonary disease actually reduces the amount of atelectasis that develops due to hyperinflation of the lungs and prevents lung collapse. However, these patients develop a more severe V/Q mismatch (2).

PREVENTATIVE MEASURES

Prevention of atelectasis starting at induction of anesthesia is important. • Induction: – Application of CPAP (6 cmH2O) for 5 minutes prior to induction, followed by mechanical ventilation with PEEP has been suggested to be superior to PEEP alone (1). – Although studies have suggested that using lower FIO2 during preoxygenation prevents

atelectasis formation during induction, it is not recommended. The apnea time before hypoxia develops is decreased; hence the margin of safety is decreased (6). • Intraoperative: – Lower levels of FIO2 may decrease absorption atelectasis (6).

– Application of PEEP (6 cmH2O) can prevent formation of atelectasis and reduction of FRC

(increased lung volume and oxygen storage) (2). It may also be an effective strategy to avoid atelectasis when higher FiO2 is required.

PREOPERATIVE ASSESSMENT • Atelectasis should be considered whenever there are alterations in lung physiology in a setting where atelectasis is likely. • Hypoxemia secondary to atelectasis is reflected in an increased A-a gradient. It is important to note other causes of hypoxemia, as seen below in differential diagnosis. • Confirmation of the diagnosis, if needed, can be obtained with imaging. – On CXR, atelectasis will have features similar to consolidation with opacification of the lung parenchyma (3). – CT scan is superior to CXR based on the resolution, and ability to measure whole and regional lung volumes. Atelectasis on CT scan has been defined as pixels with attenuation values of –100 to +100 Hounsfield units (a measure of density as seen on CT) (3). – Thoracic ultrasound is emerging as a way to rapidly assess regional consolidation (3).

DIFFERENTIAL DIAGNOSIS

Atelectasis should be distinguished from other causes of hypoxemia including:

• Hypoxic delivery • Hypoventilation • Diffusion impairment • Right-to-left intracardiac shunting

TREATMENT • A vital capacity maneuver (VCM) can offset the atelectasis that develops after induction of general anesthesia. A pressure of 40 cmH2O maintained for 7–8 seconds is needed to re-

expand previously collapsed lung tissues (2). – Laparoscopy: The recruitment effect of a single VCM may be lost after pneumoperitoneum and requires additional maneuvers to keep the alveoli open (5). – Lower FIO2: When the inflation and succeeding ventilation are performed with a lower FIO2, atelectasis reappears more slowly. One study demonstrated that when 40% was

used, only 20–25% of the initial area was atelectatic 40 minutes after the VCM. When 100% oxygen was used, however, atelectasis recurred within 5 minutes (7). – Drawbacks of VCM include a decreased preload, and potentially cardiac output. • A PEEP of 10 cmH2O will consistently reopen collapsed lung tissue. However, those lung units may re-collapse after discontinuation of PEEP. It has been shown that PEEP applied immediately following a VCM will completely prevent recurrence of atelectasis, even when 100% oxygen is used (2). • Postoperatively, techniques or devices that encourage or force patients to inspire deeply are beneficial, with a goal of producing a large, sustained increase in transpulmonary pressure to distend and re-expand collapsed lung units. Techniques include intermittent positivepressure breathing, deep-breathing exercises, incentive spirometry, and chest physiotherapy. All these techniques were shown to be equally efficacious in reducing the frequency of PPC following abdominal surgery (3).

FOLLOW-UP • Most perioperative atelectasis resolves within 24 hours after surgery (2). However, the normal coordination of respiratory muscle action is disrupted in the postoperative period, and this predisposes to decreases in FRC and VC which can contribute to development of atelectasis for days following major surgery (8). • Patients should be monitored for development of postoperative pulmonary complications.

REFERENCES

1. rismar B, Hedenstierna G, Lundquist H, et al. Pulmonary densities during anesthesia with muscular relaxation: A proposal of atelectasis. Anesthesiology. 1985;62:422–428. 2. Magnusson L, Spahn DR. New concepts of atelectasis during general anesthesia. Br J Anesth. 2003;91:61–72. 3. Duggan M, Kavanagh BP. Pulmonary atelectasis. Anesthesiology. 2005;102:838–854.

4. Griese M. Pulmonary surfactant in health and human lung diseases: State of the art. Eur Resp J. 1999;13:1455–1476.

5. Talab HF, Zabani IA, Abdelrahman HS, et al. Intraoperative ventilatory strategies for prevention of pulmonary atelectasis in obese patients undergoing laparoscopic bariatric surgery. Anesth Analg. 2009;109(5):1511–1516.

6. Reber A, Englberg G, Wegenius G, et al. Lung aeration: The effect of pre-oxygenation and hyperoxygenation during total intravenous anaesthesia. Anaesthesia. 1996;51:733–737. 7. Rothen HU, Sporre B, Engbert G, et al. Prevention of atelectasis during general anesthesia. Lancet. 1995;345:1387–1391. 8. Weiskopf RB. Preventing postoperative pulmonary complications. Anesthesiology. 2000;92:1467–1472.

9. Ho-Tai LM, Devitt JH, Noel AG, et al. Gas leak and gastric insufflations during controlled ventilation: Face mask versus laryngeal mask airway. Can J Anaesth. 1998;45:206–211. 10. Hedenstierna G, Edmark L. Mechanisms of atelectasis in the perioperative period. Best Pract Res Clin Anesth. 2010;24:157–169. See Also (Topic, Algorithm, Electronic Media Element)

• Pulmonary ventilation perfusion matching • Functional residual capacity • Surfactant • Hypoxemia intraoperatively • Postoperative pulmonary complications

CODES ICD9 518.0 Pulmonary collapse ICD10 J98.11 Atelectasis

CLINICAL PEARLS

• Ketamine is the only anesthetic that does not produce atelectasis when used alone (3). • Infants are at a greater risk for atelectasis secondary to decreased lung compliance relative to the chest wall (2). • Gastric insufflation may result from the application of PEEP during induction if peak pressures exceed 20 mm Hg (9).

ATRIA

Ali Salehi, MD

BASICS DESCRIPTION

• The atria: – House the sinoatrial (SA) node that initiates electrical impulses – Are responsible for the active filling of the ventricles during diastole – Play an important role in the neurohormonal regulation of sodium (Na+) and fluid balance

PHYSIOLOGY PRINCIPLES

• SA node: The primary pacemaker of the heart; located at the junction of the superior vena cava (SVC) and the right atrium (RA). The action potential is initiated in the SA node which has an automaticity of 70–80 pulse per minute (ppm) and a conduction velocity of 0.05 m/s. • Internodal bundles: There are 3 bundles that connect the SA node to the atrioventricular (AV) node (anterior internodal bundle of Bachman, middle internodal bundle of Wenckebach, and posterior internodal bundle of Thorel). The action potential is conducted via these bundles through both atria to the AV node simultaneously. The conduction velocity in these bundles is 0.8–1 m/s. • AV node: Located in the right posterior portion of the interatrial septum (IAS). It is the only conducting pathway between the atria and the ventricles. Its conduction velocity is slower (0.02–0.05 m/s) than the rest of the heart, allowing the ventricles sufficient diastolic filling time. The AV node can act as a latent pacemaker with an automaticity of 40–60 ppm. • His bundle: Divides at the top of the interventricular septum into the left bundle branch and right bundle branch; has an automaticity rate of 40 ppm. The left bundle divides into anterior and posterior fascicles. These bundles run subendocardially and come in contact with Purkinje fibers that spread throughout the myocardium. Conduction velocity in this system is fast (1–1.5 m/s for the bundles and 3–3.5 m/s for Purkinje fibers). • Innervation: Embryologically, the SA node develops from the structures on the right side of the heart and the AV node from the left side of the heart. This results in the SA node being innervated by the right vagus nerve and the AV node by the left vagus nerve. Sympathetic innervations (T1–T4, cardioaccelerator fibers) follow the same distribution. The majority of sympathetic fibers come from the ipsilateral stellate ganglion. • Endocrine physiology: Atrial myocytes are responsible for the production and release of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). ANP and BNP are polypeptides that are released from the atria in response to increases in extracellular fluid (ECF) volume due to Na+ retention. They function to increase the glomerular filtration rate (GFR) via renal glomerular afferent arteriole vasodilatation and efferent arteriole vasoconstriction; decrease the reabsorption of Na+ from the distal convoluted tubule and

collecting ducts (causing a net increase in Na+ excretion and volume loss); and increase capillary permeability and relax vascular smooth muscle in arterioles and venules, causing decreases in blood pressure.

ANATOMY

• The walls of all heart chambers consist of 3 layers: Endocardium (inner layer of the heart, comprises endothelial cells and subendocardial connective tissue), myocardium (middle layer of the heart, comprises myocardial muscle cells), and epicardium (outer layer of the heart, formed by the visceral layer of the pericardium). • Right atrium: The chamber forming the right upper border of the heart. – Systemic venous return from the SVC and inferior vena cava (IVC) enter the posterior, smooth wall of the RA (SVC enters at the level of the 3rd costal cartilage; IVC enters at the level of the 5rd costal cartilage on the same line as the SVC). The coronary sinus (CS) carries cardiac venous return into the posterior wall between the orifice of the IVC and tricuspid valve. The IVC is protected by the Eustachian valve and the CS is protected by the Thebesian valve. – Pectinate muscles are found on the anterior portion of the RA; they are rough, trabeculated, and made of parallel muscle bundles. – The anterior and posterior portions are separated on the right by the sulcus terminalis externally and crista terminalis internally. – The posteromedial wall of the RA is the IAS. – The base of the RA is the tricuspid valve and has 3 leaflets (anterior, posterior, and septal). • Left atrium (LA): A smooth-walled chamber that forms the base of the heart. – Receives pulmonary venous return through the right upper and lower pulmonary veins (RUPV, RLPV) and the left upper and lower pulmonary veins (LUPV, LLPV). – The left atrial auricle (LAA), or appendage, forms the superior part of the left border of the LA and has a rough trabeculated wall comprising pectinate muscles. – The LA wall is slightly thicker than the RA. – Unlike the right-sided veins, pulmonary veins do not have valves. • Interatrial septum: Separates the 2 chambers and extends posteriorly and to the right causing most of the LA to be posterior to the RA. – Embryologically, the IAS is formed by the septum primum and septum secundum (1). – The septum primum starts to develop in the 5th week of gestation and grows towards the endocardial cushion (1). – The septum secundum, at the same time, develops to the right of the septum primum as an invagination of the atrial wall. It stops growing in the 7rd week of gestation. It leaves a posterior inferior gap called the “fossa ovalis (1).” – The lower portion of the septum primum persists into adulthood as the “flap valve." Upon birth and expansion of the lungs, right-sided pressures drop below left-sided pressures and the flap valve is pressed against the septum secundum. In 66% of people they fuse together forming the “fossa ovalis." In 33% they fail to fuse resulting in a “patent foramen ovale” (PFO) (1).

DISEASE/PATHOPHYSIOLOGY

• Abnormal pulmonary venous return (congenital defect): One or more pulmonary veins that carry oxygenated blood from the lungs enter the RA instead of the LA; this can be partial anomalous pulmonary venous return (PAPVR) or total anomalous pulmonary venous return (TAPVR). PAPVR presents with symptoms of right-sided volume overload, pulmonary hypertension, and right heart failure. TAPVR is a cyanotic disorder and a true surgical emergency needing an atrial septostomy in the newborn. Since all of the pulmonary venous flow returns to the RA, presence of an atrial septal defect (ASD) or patent ductus arteriosus (PDA) is essential to sustain life after birth. • Atrial septal defect: An abnormal connection between the LA and RA that is associated with a left-to-right shunt. Patients present with symptoms of right-sided volume overload (JVP elevation, hepatic congestion, lower extremity edema, shortness of breath, pulmonary congestion). Over time, if not corrected, it can cause right ventricle (RV) failure and elevation of RA pressures with resultant shunt reversal (right-to-left shunt; Eisenmenger’s syndrome). This will lead to hypoxemia and cyanosis. There are 4 major types: – Septum secundum ASD: Results from inadequate growth of the septum secundum, enlarged foramen ovale, or excessive absorption of the septum primum. Most common ASD (80–90%), usually seen in women in the 5th or 6th decade of life, and rarely associated with other cardiac defects (1). – In addition to the septum primum, the endocardial cushion is responsible for the development of the medial portion of the mitral and tricuspid valves, and the inlet portion of the interventricular septum. A complete endocardial cushion defect is associated with a septum primum ASD, a common AV valve, and an inlet VSD. It comprises 2–3% of all ASDs and can be associated with a mitral (anterior leaflet) or tricuspid valve (septal leaflet) cleft (1). – Sinus venosus ASD: The failure in separation between the right-sided pulmonary veins and the SVC, IVC, or RA. It comprises 2–10% of all ASDs. The superior type is a defect at the junction of the SVC and RA leading to anomalous pulmonary venous return of the RUPV into the RA. The inferior type is a defect in the junction of the IVC and RA leading to anomalous pulmonary venous return of the RLPV into the RA (1). – Coronary sinus ASD: Results from the unroofing of the CS which leads to a connection between the inferior part of the LA and CS; associated with left-sided SVC. It is the least common form. • Atrial bradycardia: Sinus bradycardia (SB) is a heart rate <60 bpm. It can be seen normally in athletes due to preconditioning and increased stroke volume due to exercise. SB can also result from conditions involving the SA node such as inferior myocardial infarction; medications (beta-blockers, inhalational anesthetic agents, narcotics, anticholinesterase agents, and succinylcholine); and vagus nerve stimulation from carotid sinus message, tension on the extra-ocular muscles (oculocardiac reflex) or omentum. Additionally, reflex bradycardia can result from a sudden rise in BP that is detected by the carotid sinus. Causes include a rise in intracranial pressure (Cushing’s reflex from tumors, intracranial bleed), use of alpha-agonists (phenylephrine, norepinephrine), and increases in cardiac output. • Atrial tachycardia is a heart rate >100 bpm with a narrow complex QRS on ECG. – Sinus tachycardia is due to an increase in output (automaticity rate) of the SA node. Heart rate is usually 100–180 bpm with a “P” wave seen on the ECG. Common causes include

sympathetic stimulation (hypoxia, hypercarbia, acidosis, ischemia), hypotension or hypovolemia, anemia, anxiety, fever, anaphylactic reactions, sepsis, medications (dopamine, epinephrine), hyperthyroidism, and physical activity. – Supraventricular tachycardia (SVT) includes all forms of tachycardia originating above the bifurcation of the His bundle. They have a regular rate of 150–220 bpm. The most common type is AV nodal re-entrant tachycardia (60%). Another 30% are due to an AV re-entry pathway connecting the atria to the ventricles. The remaining etiologies include pre-excitation syndromes such as Wolff–Parkinson–White and paroxysmal atrial tachycardia. – Atrial flutter occurs at a rate of 200–350 bpm. It is usually associated with a circuit movement of the right atrial tissue causing the saw tooth pattern on ECG. Atrial flutter is almost always associated with a 2:1 or greater AV block because the AV node is not able to conduct more than 220 bpm. – Atrial fibrillation occurs at a rate of 300–500 bpm in a completely irregular and disorganized fashion. It is the result of multiple, concurrent, circulating re-entrant excitation waves in both atria; seen as an irregular pattern of AV node conduction at irregular intervals about 80–160 bpm. A-fib can be acute, chronic, or paroxysmal. Most of the foci responsible for a-fib appear to originate from atrial smooth muscle at the junction of the pulmonary veins and the LA. Other foci that can be involved include the mitral valve isthmus, orifice of CS, and SVC. • Conduction abnormalities: – First-degree heart block: All impulses are conducted to the ventricles but the PR interval on the ECG is prolonged. – Second-degree heart block (2 types): Type 1 (Wenckebach) is associated with gradual prolongation of the PR interval and eventual drop of a ventricular beat. Type 2 has a normal PR interval with sudden dropped ventricular beats; it has the potential to progress into complete heart block. – Third-degree (complete) heart block is associated with total dissociation of the atria and ventricles. The ventricles beat at a rate lower than the atrial rhythm. The block can be at the level of the AV node (nodal block) or lower (infranodal). In nodal block the remaining AV node becomes the pacemaker of the ventricles at a rate of 40–50 bpm. In infranodal block the pacemaker will be further down the conduction system with a lower rate of 15– 30 bpm which can result in significant hypotension, dizziness, and syncope. Complete heart block usually occurs due to myocardial infarction, cardiac surgery, or ventricular septal defects. – Right or left bundle branch block (RBBB, LBBB): Impulse is conducted through the intact bundle into the normal side and then through the ventricular myocardium to the blocked side. Ventricular rate is normal but there is a wide QRS complex on the ECG.

PERIOPERATIVE RELEVANCE

• Sinus bradycardia: Intraoperative medical management should be administered when associated with hemodynamic changes; treatment may include anticholinergic agents (atropine, glycopyrrolate), beta-agonists (isoproterenol), and volume resuscitation. If medical management fails, the use of temporary pacing devices should be considered, such as cutaneous pacing pads, esophageal pacing leads, intravenous pacing wires and pacing

pulmonary artery catheters (PAC, or epicardial pacing placed prior to closure of the chest in cardiac surgery). • LBBB: Avoid placement of a PAC due to the risk of complete heart block. Detection of a new onset LBBB in the perioperative period is suggestive of an ischemic event. • Atrial contraction (P wave on ECG) is responsible for 20% of LV filling during diastole. This percentage increases in patients with mitral stenosis (30%) and aortic stenosis (40%), so maintaining sinus rhythm in these patients is of utmost importance. If a-fib or atrial flutter occurs, medical or electrical cardioversion should be attempted. If attempts for cardioversion are unsuccessful, ventricular response rate should be controlled to allow for adequate ventricular filling. • Atrial tachycardias in the perioperative period should be managed based upon the appropriate ACLS protocols. • Serum BNP level is an indicator of heart failure. Normal serum BNP levels are <100 pg/dL. Levels >100 pg/dL suggest heart failure. Its sensitivity, specificity, and positive predictive value are higher than cardiomegaly on CXR or rales on physical exam in diagnosing heart failure. It also serves as an objective means to assess treatment.

GRAPHS/FIGURES

• SVC: Superior Vena Cava • AAo: Ascending Aorta • RAA: Right Atrial Appendage • CT: Crista Terminalis • ER/EV: Eustachian Valve/Eustachian Ridge • CS/ThV: Coronary Sinus/Thebesian Valve • SI: Septal Isthmus • STV: Septal leaflet of Tricuspid Valve • RV: Right Ventricle • RCA: Right Coronary Artery • OF: Oval Fossa (Fossa Ovalis)

REFERENCES

1. Rojas CA, El-Sherif A, Medina HM, et al. Embryology and Developmental defects of the interatrial septum. Am J Roentgenol. 2010;195(5):1100–1104.

2. Linton NWF, Dubrey SW. Narrow complex tachycardias. Postgrad Med J. 2009;85:546– 551.

ADDITIONAL READING

• Costanzo LS. Physiology, 4th ed. Philadelphia, PA: Elsevier, 2010, chap. 4, 111–181. • Ganong WF. Review of medical physiology, 20th ed. New York, NY: McGraw-Hill Companies, 2001, chap. 24, 439–451. • Ganong WF. Review of medical physiology, 20th ed. New York, NY: McGraw-Hill Companies, 2001, chap. 28, 528–544. • Moore KL, Dalley AF, Agur AMR. Clinically oriented anatomy, 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2010, chap. 1, 135–160.

See Also (Topic, Algorithm, Electronic Media Element) • Atrial fibrillation • AV conduction blocks • Vagal response • Tachycardia • Bradycardia

CLINICAL PEARLS

The atria of the heart function as priming pumps, house the sinoatrial node, and are involved in several congenital and rhythm disturbances.

ATRIAL FIBRILLATION Andrea Vanucci, MD, DEAA Ivan M. Kangrga, MD, PhD

BASICS DESCRIPTION

• Atrial fibrillation (AF) is a supraventricular arrhythmia characterized by uncoordinated atrial activation and consequent deterioration of mechanical function. • AF is associated with a high risk of stroke as well as increased mortality and health expenditures; as such, it is a major public health issue. EPIDEMIOLOGY Incidence

• General population: ∼1% per year – Age <40 years: ∼0.1% per year – Age >80 years: ∼2% per year (1)[A] • Postoperatively: – Noncardiac surgery: Up to 8% – Thoracic surgery: Up to 30% – Cardiac surgery: Up to 46% (2)[A]

Prevalence

About 2.2 million patients in the US and 4.5 million in the European Union have either persistent or paroxysmal AF (1)[A] Morbidity

• Stroke, cerebral thromboembolic complications, myocardial ischemia, CHF, hypotension • Ischemic stroke: 5% per year (2–7 times more frequently than those without AF)

Mortality

• Doubled compared to age-matched controls in NSR • Related to the severity of underlying heart disease • Congestive heart failure is a strong predictor of mortality • Only a minority of patients die of thromboembolic complications

ETIOLOGY/RISK FACTORS

• Cardiovascular: HTN, CAD, CHF, valvular (mitral stenosis), and pericardial heart disease • Non-cardiovascular: DM, hyperthyroidism, alcohol abuse, COPD, age • Iatrogenic: Surgery, medications (beta-agonists, cold medications, antihistamines, local anesthetics) • Familial: Na+ and K+ channel mutations

• Perioperative: Atrial injury or ischemic inflammation, increased adrenergic tone, atrial stretch from volume overload, and electrolyte disturbances

PATHOPHYSIOLOGY

• Re-entry is the main electrophysiologic mechanism of AF, and is secondary to structural or electrical remodeling. • Atrial dilation and inflammation can result in interstitial fibrosis and is the most common substrate predisposing to AF. • Channelopathies involving both K+ and Na+ channels are responsible for most familial forms of AF. • Triggers include alcohol, sleep deprivation, emotional stress, caffeine, and exercise.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintain rate control in patients presenting with AF; maintain NSR in patients with recurrent or paroxysmal AF. • Perioperative anticoagulation strategy should balance the risk of bleeding related to the type of surgery and the individual patient’s risk of thrombosis (3)[B]. • Optimization of comorbidities • Implement preventative strategies in surgical patients who are at a high risk for the development of AF (e.g., thoracic and cardiac procedures).

PREOPERATIVE ASSESSMENT SYMPTOMS

• Palpitations, shortness of breath • Neurologic symptoms

History

• Duration and type of AF (see “Classification”) • Assess CHADS2 score

Signs/Physical Exam

• Irregularly irregular heart rate • Signs of CHF, orthopnea, heart murmurs and gallop, rales and crackles • Consider common comorbidities: COPD, hyperthyroidism, DM, valvular disease

TREATMENT HISTORY

• Length of treatment • Antiarrhythmics: Class, efficacy, side effects • Previous electrical cardioversion • Electrophysiological ablation • Percutaneous closure of the left atrial appendix • Anticoagulation regimen; INR if on warfarin

MEDICATIONS

• For rhythm control, Class III antiarrhythmics (amiodarone, sotalol) are preferred due to their decreased toxicity, however they should be used with caution in patients with LQT. For rate control, beta-blockers, calcium channel blockers, and digitalis are commonly used. • Amiodarone is effective for both rate control and pharmacological cardioversion (up to 90% success if bolused followed by infusion). It is considered safe in patients with LV dysfunction, unlike class IC drugs. Acute side effects: Hypotension, bradycardia.

• CHADS2 provides an objective score for estimating the risk of stroke in non-valvular AF. Points for individual stroke risk factors are assigned as follows: 1 point is assigned for CHF, HTN, age >75, or DM; and 2 points are assigned for a history of CVA/TIA. A CHADS2 score of 0 denotes low risk, 1–2 intermediate risk, and 3–6 high risk of stroke (4)[A]. • Anticoagulation regimens are based upon the risk of stroke (CHADS2 or other scores) and are balanced against the risk of bleeding. – Aspirin if CHADS2 score ≤1 – Warfarin if CHADS2 score ≥2 – Dabigatran is a direct selective thrombin inhibitor. Stroke prevention is equal to that of warfarin and fewer bleeding complications are seen with low doses. It is dosed twice per day, orally. For a CHADS2 score = 1, the dose is 110 mg PO and for a CHADS2 score ≥2, the dose is 150 mg PO (4)[A]. – The CHADS2 score has not been validated in valvular AF where there is a high risk of stroke; thus, anticoagulation is always required. • Statins

DIAGNOSTIC TESTS & INTERPRETATION

• Palpation or auscultation: Irregular heart rate • EKG: Uneven R-R interval with occasional f waves • CXR: Pulmonary vasculature congestion and cardiomegaly • Echocardiogram and stress testing may be considered to rule out underlying structural or ischemic myocardial disease, left atrial enlargement, thrombus, RV strain if PE is suspected. • Holter monitor in suspected paroxysmal AF or if evaluating the efficacy of rate control treatment • Pacemaker may be in place.

Labs/Studies

• Serum or whole-blood (point-of-care) INR if on warfarin, or PTT/ACT if on heparin; there is no valid point-of-care test for direct thrombin inhibitors. • Electrolytes, including magnesium • Digoxin levels • Thyroid function tests if on amiodarone • EP studies, if available

CONCOMITANT ORGAN DYSFUNCTION

Evaluate cardiopulmonary, neurologic, and endocrine systems for known associated comorbidities CIRCUMSTANCES TO DELAY/ CONDITIONS

• Poor rate control • Signs and symptoms of CHF • New-onset AF of unknown etiology (rule out ischemic or structural heart disease) • Delay DC cardioversion until therapeutic INR or TEE evidence of atrial thrombus

CLASSIFICATIONS

• Newly discovered AF is the first presentation of AF for which the actual onset is not known. • Paroxysmal and persistent AFs are both recurrent, but the former is self-terminating within 7 days, while the latter requires cardioversion to restore sinus rhythm. • Permanent AF describes unsuccessful or abandoned attempts to convert to sinus rhythm. • Etiologically, AF can be valvular or non-valvular. Patients with mitral valve disease are at an increased risk for stroke.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis as needed • Caution with possible triggering agents (glycopyrrolate, albuterol) • Ideal resting heart rate is 60–80 bpm. Consider optimizing existing antiarrhythmic therapy. • In cardiac surgery, corticosteroids should be considered; they have been shown to reduce the incidence of AF postoperatively (5)[A]. • Statins, given 7 days preoperatively, reduce the incidence of postoperative AF in thoracic and cardiac surgery, and should be considered (5)[A]. Special Concerns for Informed Consent

• Increased risk of thromboembolic or hemorrhagic (if on anticoagulant) complications • Increased risk of ventricular arrhythmias, CHF • Possible need for intraoperative DC cardioversion in recurrent AF • Possible TEE to rule out atrial clots in a patient who is not anticoagulated

INTRAOPERATIVE CARE Choice of Anesthesia

• Regional or neuraxial anesthesia may be contraindicated due to anticoagulants. If warfarin has been held for surgery, PT/PTT/INR should be checked prior to placement. In patients with thrombin inhibitors (Dabigatran) ASRA recommends against the use of neuraxial anesthesia. • For MAC cases, consider dexmedetomidine to maintain rate control.

Monitors

• Noninvasive BP measurement is adequate for most routine cases. Highly irregular pulses may result in the NIBP cuff reading taking more time to cycle and may give unreliable measurements. • Arterial line is not necessary in stable hemodynamics and routine cases. However, a lower

threshold should exist for placing an arterial line when hemodynamic instability is anticipated. • Central venous catheters, pulmonary artery catheters, and TEE may be indicated based on the type of surgery and comorbidities. TEE is a superior monitor of preload and contractility, particularly in the absence of atrial contraction. TEE may be beneficial in guiding fluid administration and vasopressor therapy in critical patients with AF. • Esophageal Doppler and arterial pressure based cardiac output monitors do not work well in AF.

Induction/Airway Management

• Avoid excessive sympathetic stimulation prior to airway management by ensuring adequate: – Depth of anesthesia with induction agents, volatile agents, opioids, and lidocaine – Oxygenation and ventilation – Time for full onset of muscle relaxants when intubating • Have rate control drugs ready and available

Maintenance

• MAC/sedation: Caution with, or avoidance of, epinephrine in local anesthesia • General anesthesia may be provided with either a balanced inhalational or intravenous technique. • Rate control: Adequate depth of anesthesia, cautious use of positive chronotropes (e.g., ephedrine, albuterol, vagolytic agents, etc.) • Rapid ventricular rate (RVR) with instability warrants immediate DC cardioversion. • For RVR with hemodynamic stability, rate control may begin with diltiazem or betablockers. Reserve amiodarone for patients with poor LV function. Caution: Amiodarone may convert into NSR and “eject” a clot into the systemic circulation. • New-onset AF: Pharmacological conversion if stable, DC cardioversion if unstable. Caution: Successful DC cardioversion may still require anticoagulation due to atrial stunning.

Extubation/Emergence

• Avoid excessive sympathetic stimulation (see “Induction”) • Slow titration of reversal agents • Consider deep extubation, if appropriate, to avoid coughing and bucking

POSTOPERATIVE CARE BED ACUITY

• Routine postoperative care is usually appropriate in stable patients. • Telemetry or ICU care may be warranted in poorly controlled AF and hemodynamic instability.

MEDICATIONS/LAB STUDIES/ CONSULTS

• Reinstitute rate control, antiarrhythmic, and/or anticoagulants as soon as appropriate • Labs: Electrolytes, glucose in DM, INR/PTT • Troponins if underlying cause for AF is CAD

COMPLICATIONS

• RVR with hypotension, CHF • Ventricular arrhythmias • Myocardial ischemia • Bleeding versus stroke and other thrombotic complications • Postoperative cognitive dysfunction

REFERENCES

1. Fuster V, Ryden L, Cannom D, et al. 2011 ACCF/AHA/HRS Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;123(10): e269–e367.

2. Mayson SE, Greenspon AJ, Adams S, et al. The change in face of postoperative atrial fibrillation prevention. Cardiol Rev. 2007;15:231–241. 3. Mannucci C, Douketis JD. The management of patients who require temporary reversal of vitamin K antagonists for surgery: A practical guide for clinicians. Intern Emerg Med. 2006;1:96–104. 4. Medi C, Hankey G, Freedman S. Stroke risk and antithrombotic strategies in atrial fibrillation. Stroke. 2010;41:2705–2713. 5. Jongnaranggsin K, Hakan O. Postoperative atrial fibrillation. Med Clin N Am. 2008;92:87– 99.

ADDITIONAL READING

• Horlocker T, Wedel D, Rowlingson J, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010;35:64– 101. • Kaatz S, Douketis JD, Zhou H, et al. Risk of stroke in patients with and without chronic atrial fibrillation. J Thromb Haemost. 2010;8:884–890. • Lip GH, Huang-Fat T. Management of atrial fibrillation. Lancet. 2007;370:604–618.

See Also (Topic, Algorithm, Electronic Media Element) • Atrial flutter • Cerebrovascular disease • Postoperative stroke • Perioperative statins

CODES ICD9 427.31 Atrial fibrillation

ICD10

• I48.0 Paroxysmal atrial fibrillation • I48.2 Chronic atrial fibrillation • I48.91 Unspecified atrial fibrillation

CLINICAL PEARLS

• Assess for the underlying structural, valvular, or coronary artery ischemic disease. • Perioperative anticoagulation and rate control management should be addressed in consultation with the surgeon, anaesthetist, and cardiologist. • Risk of stroke is higher in valvular AF. • Atrial thrombi may be seen in 14% of patients in whom AF lasted >2 days. • Statins may be protective: Risk of postoperative AF is inversely related to the duration of preoperative statin prophylaxis. Additionally, statins improve outcomes in the surgical ablation of AF.

ATRIAL FLUTTER

Mirsad Dupanovic, MD Svjetlana Tisma-Dupanovic, MD

BASICS DESCRIPTION

• Atrial flutter (AFL) is a paroxysmal, regular, macro re-entrant arrhythmia most often occurring in patients with structural heart disease. The re-entrant circuit is classically confined to the right atrium with typical rates from 240 to 320 beats per minute (bpm). • Ventricular rate is determined by AV node conduction; thus a 2:1 AV block results in a ventricular rate of 120–160 bpm. Rapid AV node conduction is responsible for hemodynamic deterioration and AFL-related fatalities. • AFL is usually short-lived and closely related to atrial fibrillation (AF). If present for a prolonged period, AFL usually evolves to AF. EPIDEMIOLOGY Incidence

• Incidence of ∼1% in the general population • Incidence >5% in patients >80 years old

Prevalence

Uncertain since AFL is rarely a chronic condition Morbidity/Mortality

• Based on the integrity of the myocardial conduction system, ventricular function, age at presentation, duration of arrhythmia, and presence of other coexisting diseases. • Associated with a 1.7-fold increase in mortality over a mean period of 3.6 years. The risk is higher if AFL coexists with AF. ETIOLOGY/RISK FACTORS

• Male gender: AFL ∼5-fold more common in men. • Cardiac procedures: – Pericarditis following cardiac surgery can lead to atrial inflammation and AFL. – Myocardial scar formation following atrial ablation procedures can instigate AFL. • Cardiovascular diseases: – Structural heart disease leading to right atrial enlargement (valvular heart disease, pulmonary embolism, or cardiomyopathy). – Slowing of cardiac conduction (fibrosis or antiarrhythmic agents). • Other disease: Chronic obstructive pulmonary disease (COPD), thyrotoxicosis, and chronic alcoholism. • Iatrogenic: Digitalis toxicity.

PATHOPHYSIOLOGY

• AFL describes a class of re-entrant arrhythmias localized to the atria. – Typical AFL (isthmus-dependent, Type I): Right atrial re-entrant circuit that travels around the tricuspid valve either counterclockwise or clockwise. The flutter wave circuit is bounded by the caval veins, crista terminalis, and the Eustachian ridge (the “isthmus” of slow conduction). The direction of the re-entry circuit determines polarity of typical “sawtooth” flutter waves (Ta). The Ta waves, which reflect atrial repolarization, are positive in the inferior leads with counterclockwise re-entry. Clockwise re-entry results in negative Ta deflection

in the inferior leads. If discernable, P’ waves (atrial depolarization) have reverse polarity in the same leads. Cycle length of 200–400 ms depends on atrial size and the presence of antiarrhythmic drugs. – Atypical AFL (non-isthmus dependent, Type II): Right or left atrial re-entrant circuits that travel around a region of atrial scarring. Atrial scar secondary to myocardial disease, surgical procedure, or extensive radiofrequency atrial ablation. Difficult to treat: Ablation, cardioversion, and pharmacologic interventions are often unsuccessful. • AV conduction ratio (1:1, 2:1, 4:1, 6:1) influences the physiologic consequences of AFL. – 1:1 AV node conduction results in a rapid ventricular rate and hemodynamic compromise. Occurs in the setting of accessory pathways or exogenous catecholamines. Rapid ventricular rate may lead to myocardial ischemia, malignant ventricular arrhythmias, and death. – 2:1 AV node conduction results in a fixed and regular ventricular rate. – Variable AV block produces an irregular ventricular rhythm. Occurs with nodal disease, increased vagal tone, and in the presence of nodal blocking agents. • AFL and AF have similar pathophysiology and coexist in many patients. – ∼50% of patients with AFL will develop AF over a 5-year period. – The arrhythmia-related “remodeling” caused by one arrhythmia AFL leads to progression of the other AF. “Remodeling” is characterized by structural (increased atrial size), electrical (shortening of atrial refractory period), and ultrastructural (promoting atrial fibrosis) changes.

Pediatric Considerations

• AFL with atrial rates of 400–600 bpm and 2:1 conduction is common in neonates. Termination of the arrhythmia can be accomplished with transesophageal pacing or external synchronized cardioversion. • Mustard, Senning, or Fontan cardiac procedures dramatically increase the risk for development of AFL.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The underlying medical condition or inciting event should be optimized.

• Control the ventricular rate to enhance ventricular filling and sufficient stroke volume. – Calcium channel blockers or beta-blockers can be used to increase AV conduction block and slow ventricular rate. – Carotid sinus massage may increase the AV conduction ratio and temporarily slow the ventricular rate. • Conversion to sinus rhythm via synchronized cardioversion: – Monophasic shocks in the following sequence: 100 J, 200 J, 300 J, 360 J. – If AFL duration is >48 hours, confirmation via transesophageal electrocardiography (TEE) to confirm the absence of atrial thrombus and/or anticoagulation must precede cardioversion. • Anticoagulation is typically via heparin or warfarin. – Patients with AFL are at similar risk of stroke as patients with AF and should be anticoagulated if AFL lasts >48 hours.

PREOPERATIVE ASSESSMENT SYMPTOMS

• The hemodynamic consequences of AFL depend on the flutter rate, AV conduction ratio, ventricular rate, and presence of ventricular dysfunction. • Symptoms depend on the ventricular rate. – Increased ventricular rates (1:1 or 2:1 AV conduction) are often perceived as palpitations, chest discomfort, or dizziness. – Decreased ventricular rates (8:1 AV conduction) may manifest as fatigue and exercise intolerance.

History

• Evaluation of risk factors: Open heart surgery, cardiac valvular disease, myocardial ischemia, pulmonary embolism, COPD, hyperthyroidism, and/or digitalis toxicity. • History of AFL: Duration, current management, and previous treatment. • Presence of coexisting diseases: Pharmacologic management depends on myocardial function.

Signs/Physical Exam

• Tachycardia with regular, usually fixed, ventricular rate of 140–160 bpm. Irregularly irregular pulse is rare, but may occur if AV conduction ratio is variable. • Rapid, rippling flutter waves may be seen in the jugular venous pulse with an AV conduction ratio of 4:1 but not with 2:1 ratio. • Cardiac decompensation leads to dyspnea, hypoxemia, rales, and crackles. • Previous radiofrequency ablation – AFL ablation has a >90% long-term success rate. Best results are seen with isthmusdependent AFL, normal right atrial size, and no history of AF.

MEDICATIONS

• Rate control: Amiodarone, diltiazem, verapamil, or beta-adrenergic blockers slow down AV conduction and control the ventricular rate.

– Amiodarone, diltiazem, and digoxin are preferred in the presence of impaired myocardial function. – Beta-blockers are effective in the setting of increased sympathetic tone and thyrotoxicosis. – Vagolytic effects of class I antiarrhythmic drugs administered for AFL may result in reduction of atrial rate to 180-200 bpm, consequential 1:1 AV nodal conduction, and resultant increase of ventricular rate. Thus, AV blocking drugs should be administered before the administration of class I antiarrhythmic drugs. • Convert rhythm: Ibutilide, amiodarone, dofetilide, sotalol, flecainide, propafenone, procainamide, and disopyramide have variable success (50–60%) in terminating AFL. • Approximately 15% of patients treated with class IC antiarrhythmic agents or amiodarone for AF will develop AFL. This led to the development of a “hybrid" management strategy of antiarrhythmic drugs to treat AF with subsequent ablation to treat AFL.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Labs: Electrolytes, cardiac enzymes, digoxin level, and thyroid function tests. • ECG: Atrial rate ranges from 240 to 340 bpm, “sawtooth” pattern in the inferior leads, and regular ventricular response with a discernable and consistent relationship between flutter waves and QRS complexes. – Flutter waves can be obscured by the T waves. Infusion of adenosine or vagal maneuvers will briefly stop or decrease AV conduction, allowing recognition of the flutter waves. – In the setting of an accessory pathway, the ECG pattern is indistinguishable from ventricular tachycardia, even with 2:1 conduction. – Atrial rate of >340 bpm may be seen with atypical AFL. • Echocardiogram: Evaluate atrial size and ventricular function – TEE is used to evaluate for the presence of atrial thrombus prior to synchronized cardioversion in patients with AFL lasting longer than 48 hours.

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Uncontrolled ventricular rate, myocardial ischemia, or cardiac decompensation. • Synchronized cardioversion in hemodynamically unstable patients.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics can decrease sympathetic output. • Rate control: Calcium channel blockers or beta-adrenergic blockers can be titrated to effect.

Special Concerns for Informed Consent

• Increased risk of intraoperative rapid ventricular rate, myocardial ischemia, cardiac decompensation, and thromboembolic events. • Risks and benefits of delaying the surgery to evaluate and treat paroxysmal AFL must be

explained. Non-urgent surgery should be postponed until adequate control of the ventricular rate has been achieved.

INTRAOPERATIVE CARE Choice of Anesthesia

Insufficient evidence to suggest that either general or regional anesthesia is preferred for patients with AFL. Monitors

• Standard ASA monitors including ECG with ST segment analysis. • Arterial catheter for close monitoring of blood pressure or frequent blood gas evaluation. • Central venous catheter for infusion of vasopressors or transvenous pacing. • Pulmonary artery catheter for evaluation of cardiac output or mixed venous oxygenation, if indicated. • Transesophageal echocardiography, if indicated.

Induction/Airway Management

• Risk of hemodynamic instability – Vasodilation and myocardial depression from induction agents (propofol and thiopental). – Sympathetic stimulation from laryngoscopy. – Dexmedetomidine is associated with prolonged hypotension and increased AV nodal blockade. • Avoid pharmacologic agents associated with sympathetic activation (ketamine) or vagolytic effects (pancuronium).

Maintenance

• Use of either volatile anesthetic or total intravenous anesthetic is acceptable. • Conservative fluid management in the setting of reduced myocardial function. • Intraoperative occurrence may be treated with rate control medications, vagal maneuvers, or cardioversion if the patient is hemodynamically unstable.

Extubation/Emergence

• Avoid sympathetic stimulation. • Ensure adequate analgesia. • Balance reversal of neuromuscular block (excessive anticholinergics can provoke AFL); consider slow titration to reduce incidence.

POSTOPERATIVE CARE BED ACUITY

ICU with hemodynamically unstable or poorly controlled AFL MEDICATIONS/LAB STUDIES/ CONSULTS

• Medications: Rate control agents and anticoagulation as indicated. • Labs: Electrolytes, digoxin level, cardiac enzymes, and thyroid function tests.

COMPLICATIONS

• Systemic thromboembolism • Coronary and/or cerebral ischemia secondary to hemodynamic insufficiency • Tachycardia-induced cardiomyopathy • Sinus bradycardia following administration of AV nodal blocking agents

REFERENCES

1. Lee KW, Yang Y, Scheinman MM. Atrial flutter: A review of its history, mechanism, clinical features, and current therapy. Curr Probl Cardiol. 2005;30:121–168.

2. Nattel S, Singh BN. Evolution, mechanisms, and classification of antiarrhythmic drugs: Focus on class III actions. Am J Cardiol. 1999;84:11R–19R.

3. Van Gelder IC, Hagens VE, Bosker HA, et al. Pharmacologic versus direct-current electrical cardioversion of atrial flutter and fibrillation. Am J Cardiol. 1999;84:147R–151R. See Also (Topic, Algorithm, Electronic Media Element) • Atrial fibrillation • Electrical cardioversion • Wolff–Parkinson–White

CODES ICD9 427.32 Atrial flutter ICD10 • I48.3 Typical atrial flutter • I48.4 Atypical atrial flutter • I48.92 Unspecified atrial flutter

CLINICAL PEARLS

• Atrial flutter (AFL) commonly occurs in patients after open heart surgery and those with underlying cardiac disease. • ECG manifestations include flutter waves with variable AV conduction. • Ventricular rate control is achieved with beta-blockers or calcium channel blockers. • Hemodynamically unstable patients require immediate synchronized cardioversion.

ATRIAL SEPTAL DEFECT (ASD) Jason Choi, MD John G. T. Augoustides, MD, FASE, FAHA

BASICS DESCRIPTION

• A defect of the interatrial septum that allows communication between the right and left atria. It is the most common congenital heart defect in adults. • 3 types: – Ostium secundum (75% of all ASDs): Patent foramen ovale (PFO) is a subtype of ostium secundum and is the most common ASD. – Ostium primum (15%): Associated with mitral regurgitation from the cleft mitral valve – Sinus venosus (10%): Associated with anomalous partial drainage of the pulmonary veins into the right atrium or superior vena cava • ASD is often benign and asymptomatic until the 4th or 5th decade of life. Virtually all adults with an ASD become symptomatic by the 6th decade. – Moderate or severe defects present in a child with congestive heart failure (CHF). – First presentation of ASD in adults may be a stroke or transient ischemic attack (TIA). – Diagnosis is common during pregnancy due to increased blood volume. • Clinical sequelae of ASD correspond to the degree and direction of shunting. – Most common is left-to-right cardiac shunt. – Right-to-left shunt indicates a more severe disease. – PFO is the main cause of transient right-to-left shunt and paradoxical emboli. EPIDEMIOLOGY Incidence

ASD is diagnosed in 1 out of 1,500 live births. Prevalence

• ASDs account for 10% of all congenital heart diseases and 30% of adult congenital heart diseases (1)[A]. • ASDs are 2–3 times more common in women. • PFOs present in about 25% of adults (2)[A]. A majority of PFOs are undiagnosed.

Morbidity

• ASDs have low morbidity. • Pulmonary hypertension is rarely seen before the 3rd decade of life (3)[B].

Mortality

• ASDs are associated with low mortality. • Decreased life expectancy is seen with ASD, but patients can reach advanced age without

intervention. Mortality rate from ASD repair is close to zero if performed before the 4th decade in patients without significant pulmonary hypertension (2)[B].

ETIOLOGY/RISK FACTORS

• Spontaneous genetic mutations lead to aberrant embryologic septal development (4)[B]. • Inheritance of ASD is not fully understood. • Ostium primum is associated with Down syndrome. • CHF symptoms in an infant with ASD indicate additional congenital heart defects (3)[C].

PATHOPHYSIOLOGY

• Size of defect, ventricular compliance, and direction of venous inflow determine the degree and direction of interatrial shunting. – Defects <5 mm are hemodynamically insignificant, while defects >20 mm cause clinically significant shunting (1)[A]. • Left-to-right shunt is a result of greater right ventricle compliance and lower pulmonary vascular resistance (PVR). – Chronic left-to-right shunt increases pulmonary blood flow and can lead to pulmonary vascular congestion and right ventricular strain. – Severe pulmonary hypertension and right heart failure may develop. Pulmonary flow can reach 4 times that of systemic flow in severe disease. Right-to-left shunt (Eisenmenger syndrome) can develop over time secondary to increased pulmonary pressures. This “shunt reversal” results in cyanosis as a significant fraction of blood bypasses the pulmonary circulation and gets ejected into the systemic circulation, unoxygenated. • Patients most commonly present with dyspnea, palpitations, and decreased exercise tolerance. Atrial arrhythmias, especially atrial fibrillation, are commonly seen in the 4th decade. • PFO is unique as a dynamic shunt occurring under certain physiologic situations that transiently elevate right atrial pressures (e.g., coughing, Valsalva maneuver, and increased PVR). – All other ASDs can have transient right-to-left shunting, but usually shunt left-to-right continuously.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Decrease the risk of paradoxical emboli (e.g., avoid air entry in IV lines). • To prevent worsening of left-to-right shunt, avoid increases in systemic vascular resistance (SVR), fluid overload, steep Trendelenburg positioning, and over-transfusion. • Be aware of scenarios that cause transient right-to-left shunting: Pulmonary embolism, high positive end-expiratory pressure (PEEP), venous air embolism, pneumoperitoneum with laparoscopy, and cardiac tamponade. • Be prepared to treat pulmonary hypertension with direct pulmonary vasodilators.

PREOPERATIVE ASSESSMENT SYMPTOMS

• ASD is an acyanotic defect (left-to-right shunt).

• Cyanosis and clubbing with only an ASD reflect right-to-left shunt and severe disease. • Atrial fibrillation • CHF symptoms: Orthopnea

History

• Clinical presentations of ASD vary. • ASD is often undiagnosed until adulthood due to a lack of symptoms and physical findings. • Rule out a history of stroke, TIA, new onset dyspnea on exertion, and palpitations from atrial arrhythmias. • Assess progression/worsening of symptoms. • Ask about a history of murmur or previous assessment by a cardiologist.

Signs/Physical Exam

• Fixed-split S2 heart sound on auscultation is pathognomonic for ASD. • Systolic ejection murmur is heard from increased output through the pulmonic valve. • Ostium primum is associated with significant mitral regurgitation. • S4 heart sound reflects right ventricular hypertrophy and pulmonary hypertension.

TREATMENT HISTORY

Closure of the defect with open heart surgery or cardiac catheterization. If the patient has not had an ASD closure, they are most often asymptomatic. MEDICATIONS

There is no specific medical therapy.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• ECG: Incomplete right bundle branch block (invariably present), atrial arrhythmia (e.g., atrial fibrillation), prolonged PR interval, right ventricular hypertrophy, or right axis deviation • CXR: Prominent pulmonary vasculature often noted from vascular congestion • Echocardiography: Important to note the degree of shunting, size and strain of right ventricle, and pulmonary artery pressures – TEE with bubble study is the gold standard diagnostic study (4)[A]. • Cardiac catheterization: Pulmonary artery pressures should be recorded.

CONCOMITANT ORGAN DYSFUNCTION

Other organ dysfunction, such as pulmonary edema, pulmonary hypertension, or complications of right heart failure, is only seen with moderate/severe disease from ASD. CIRCUMSTANCES TO DELAY/ CONDITIONS

• Presence of right-to-left shunt requires correction or medical optimization prior to elective surgery (4)[B]. • Pulmonary blood flow >1.5 times the systemic flow warrants closure of the ASD (1)[A].

CLASSIFICATIONS

• Asymptomatic • Symptomatic left-to-right shunt • Right-to-left shunt with pulmonary hypertension

TREATMENT PREOPERATIVE PREPARATION Premedications

• For most patients with ASD, there is no restriction on premedication. • Premedication with midazolam can help with facilitating parental separation in the pediatric population. Special Concerns for Informed Consent

Risk of paradoxical emboli leading to stroke is minimal but present. INTRAOPERATIVE CARE Choice of Anesthesia

For the typical asymptomatic ASD patient, choice of anesthesia and technique can be tailored to provider and/or patient preference. Monitors

• Standard ASA monitoring • Monitors should be tailored to extent of surgery and its risks. • For open ASD repair on bypass, TEE, arterial line, and central line +/– pulmonary artery catheter are recommended for intra-operative management. Induction/Airway Management

• No special airway considerations • Drug dilution occurs from increased pulmonary blood flow, but is unlikely to have clinical relevance or to affect induction time. • There is no indication for endocarditis prophylaxis (4)[B], unless concomitant valvular disorder warrants it. Maintenance

• Imperative to prevent air emboli • Prevent increases to the left-to-right shunt – Use techniques that decrease the SVR (promotes forward flow into the aorta) or increase the PVR – Avoid a high FiO2 and hyperventilation; they can cause pulmonary vasodilatation. – Maintain higher mean airway pressures – Avoid fluid overload and over-transfusion

Extubation/Emergence

Bucking and coughing upon emergence increases the risk of paradoxical emboli by causing

transient right-to-left shunting.

POSTOPERATIVE CARE BED ACUITY

ICU postoperative care is not warranted unless the patient has significant pulmonary hypertension or has had closure of the ASD. MEDICATIONS/LAB STUDIES/ CONSULTS

If symptoms or complications of ASD manifest during the perioperative period, cardiology should be consulted. COMPLICATIONS

• Paradoxical embolism: Stroke, TIA, fat embolism • Transient supraventricular dysrhythmias and atrioventricular conduction defects are common post-closure of ASD. • Post-ASD closure, interpretation of central venous pressure (CVP) must account for a previously dilated right atrium. Maintaining normal CVP values may cause volume overload.

REFERENCES

1. Rigatelli G, Ronco F. Patent foramen ovale: A comprehensive review for pulmonologist. Curr Opin Pulm Med. 2010;16:442–447. 2. ensley FA, Martin DE, Gravlee GP. A practical approach to cardiac anesthesia, 3rd ed. Philadelphia: Lippincott Williams and Wilkins, 2003. 3. Augoustides JG, Ochroch EA. Assessment of intracardiac shunts: Perioperative echocardiography. Int Anesthesiol Clin. 2008;46:83–95.

ADDITIONAL READING

• Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: Executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2008;118(23):2395–2451.

See Also (Topic, Algorithm, Electronic Media Element) • Ventricular septal defect • Cardiopulmonary bypass • Patent foramen ovale • Venous air embolism • Chest x-ray

CODES

ICD9

• 745.5 Ostium secundum type atrial septal defect • 745.8 Other bulbus cordis anomalies and anomalies of cardiac septal closure ICD10

• Q21.1 Atrial septal defect • Q21.2 Atrioventricular septal defect

CLINICAL PEARLS

• 25% of adults have patent foramen ovale (PFO) and most are undiagnosed. • Avoid air entry in IV lines in ASD patients. • A fixed-split S2 heart sound is pathognomonic for ASD. • PFOs can transiently shunt right-to-left during the anesthetic course (high peak inspiratory pressure [PIP], coughing, abdominal insufflation, Trendelenburg positioning, etc).

ATRIAL TACHYCARDIAS Svjetlana Tisma-Dupanovic, MD Mirsad Dupanovic, MD

BASICS DESCRIPTION

• Atrial tachycardias (ATs) encompass several types of arrhythmias driven by one or more ectopic sources outside the sinus node and do not require the participation of the AV node for maintenance of tachycardia. ATs may be based on micro-reentrant, triggered, or automatic mechanisms causing focal atrial tachycardia (FAT) or multifocal atrial tachycardia (MAT) (1)[A]. • FAT may present as transient, recurrent, sustained, and incessant with usual rates of 130– 250 bpm. MAT may be persistent and easily misinterpreted as atrial fibrillation (2)[A]. EPIDEMIOLOGY Prevalence

FAT accounts for 5–15% of patients undergoing electrophysiologic studies. The rates are higher in children (1)[A].

Prevalence

• FAT: 0.34% in asymptomatic individuals and 0.46% in symptomatic patients (1)[A] • MAT in the hospitalized population has been estimated to be 0.05–0.32% (2)[A].

Morbidity/Mortality

• Incessant AT may result in dilated cardiomyopathy, which may be reversible after the tachycardia has been terminated. • Patients being hospitalized with MAT are usually elderly and may have high mortality as a consequence of underlying chronic obstructive pulmonary disease (COPD) (2)[A].

ETIOLOGY/RISK FACTORS

• FAT: Open heart surgery (especially for correction of CHD), younger age, and disturbances of the autonomic nervous system • MAT: COPD, congestive heart failure (CHF), hypoxemia, use of theophylline, electrolyte abnormalities (hypomagnesemia, hypokalemia), and increased age (2)[A].

PHYSIOLOGY/PATHOPHYSIOLOGY

• FAT is characterized by atrial activation starting rhythmically at a small area (focus) from which it spreads out centrifugally. Usual locations of such foci are the area along the crista terminalis and near the right and left pulmonary veins. It may be caused by micro-reentrant, triggered, or automatic mechanisms (3)[A]. – Micro-reentry may be initiated and terminated with programmed electrical stimulation.

Verapamil, adenosine, and dipyridamole can terminate this arrhythmia. – Triggered activity may also be initiated and terminated with electrical stimulation (atrial extrastimuli or rapid atrial pacing). Verapamil, propranolol, adenosine, carotid sinus massage, and dipyridamole can terminate triggered FAT. – Automatic FAT cannot be initiated or terminated with programmed electrical stimulation, but it can be initiated by isoproterenol infusion and terminated with propranolol. The rhythm is insensitive to adenosine, verapamil, and carotid sinus massage. Episodes of automatic FAT commonly show a “warm-up” phenomenon at the beginning (the rate gradually increases) and a “cool-down” phenomenon at termination (the rate gradually slows down with transition to normal sinus rhythm). Since automaticity decreases with aging, automatic FAT is less common in geriatric patients (1)[A]. • MAT (chaotic AT) may be initiated by delayed after-depolarizations arising from multiple atrial foci. The definition of MAT requires at least 3 distinct P’ wave morphologies (2)[A].

Pediatric Considerations

FAT during infancy is typically incessant. Patients often present with tachycardia-induced cardiomyopathy. MAT is an uncommon, well-tolerated, and self-limiting rhythm in most pediatric patients. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Drugs that modulate the autonomic nervous system may be useful in the anesthetic regimen of patients presenting with FAT. • Treatment of the underlying medical diseases is the primary and the most successful therapy for MAT. It is also important to avoid hypoxemia as well as medications or procedures that could worsen the pulmonary status. • Cardioversion has no effect on the sites of ectopy that produce automatic FAT and is not effective in converting MAT to sinus rhythm (1)[A], (2)[A].

PREOPERATIVE ASSESSMENT SYMPTOMS

• Symptoms of ATs may range from none to syncope to symptoms of heart failure. • The severity of FAT presentation depends on the ventricular rate and presence of ventricular dysfunction. • The gradual increase in heart rate at the beginning and slowing at termination may make it difficult for a patient to recognize the tachycardia. • Some patients may perceive fast ventricular rates as palpitations, chest discomfort, or dizziness. Exercise intolerance results from the inappropriately high ventricular rate that does not change with increasing workload. • Symptoms or signs of CHF are due to decreased left ventricular contractility, AV valve regurgitation, and atrial dilatation.

History

• Review for presence of a cardiac or pulmonary disease, recent heart surgery, and the arrhythmogenic effects of current medications.

• Review for previous episodes, management, and current duration of AT. • FAT may resolve spontaneously. However, failure to perceive the FAT of incessant nature can lead to depression of myocardial function and tachycardia-induced cardiomyopathy. If the tachycardia is not treated aggressively, the myocardial function can continue to decline, resulting in an irreversible cardiomyopathy. This occurs in 80% of cases due to FAT of abnormal automaticity. Patients with faster rates may be at higher risk (1)[A]. • The MAT usually occurs in elderly and seriously ill patients. It may resolve within days following successful management of the underlying disease. If management of the underlying disease is not successful, onset of MAT implies a poor prognosis. MAT may be preceded by or progress to atrial fibrillation or atrial flutter in 50% of cases. The choice of pharmacologic agents may depend on the presence of coexisting medical diseases. Signs/Physical Exam

• The pulse rate may not be reflective of the atrial rate because of variable AV node conduction. • The heart rates seen in FAT vary based on the patient’s age and catecholamine state. In case of chronic FAT the rate tends to vary from hour to hour influenced by a variety of physiologic factors modifying autonomic tone. Ventricular rate is usually regular. • In MAT, the rhythm is irregular and the physical examination findings clinically resemble atrial fibrillation. • Dyspnea, hypoxemia, rales, and crackles are signs of cardiac decompensation.

TREATMENT HISTORY

• Review type, length, success of treatment, and recurrence of symptoms • History of interventional management: Overdrive pacing and cardioversions are usually not successful in automatic FAT and MAT. • History of arrhythmia ablation: The treatment of choice for poorly controlled FAT and MAT has become radiofrequency catheter ablation. MEDICATIONS

• Termination of AT using adenosine makes it highly unlikely that automatic FAT is present. • Primary acute treatment strategy of FAT is slowing or terminating the tachycardia. AV nodal blocking is the secondary strategy. IV beta-adrenergic blockers may terminate automatic FAT while nonautomatic FATs are frequently terminated by verapamil (1)[A]. • Class I antiarrhythmic medications may decrease automaticity, prolong refractory period, and can terminate FAT. • Class III drugs that slow myocardial conduction and AV conduction have had modest success in treatment of ATs. These medications, except amiodarone, have the potential to decrease myocardial performance and must be used with caution in patients with decreased LV function. • Digoxin slows AV conduction by enhancement of vagal activity and is a positive inotropic agent. • Calcium channel blockers (Class IV drugs) slow the AV conduction, but are negative inotropes and should be used selectively and cautiously. • The management strategies of MAT also rely on suppression of the tachycardia focus and/or

slowing of AV conduction. It may take a combination of drugs to control the rate. • Metoprolol and high doses of IV magnesium can be useful in treating MAT.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, digoxin level • The majority of FATs can be diagnosed from the ECG; however, differentiation from other forms of supraventricular tachycardia (SVT) may be difficult. – FAT presents on the ECG with P’ waves that generally show an abnormal axis and configuration, but remain similar in shape. When the focus arises from the left atrium, the P’ wave is negative in lead I; those with focus in the low right atrium show a negative P’ wave axis in the lead aVF with a positive wave in lead I. Occasionally, the focus is in an area close to the sinus node or in the high right atrium and the P’ wave axis is similar to sinus tachycardia. When the rhythm resembles sinus tachycardia, it can lead to a delay in diagnosis and institution of therapy. – The atrial rate during FAT is generally between 100 and 180 bpm. Each P’ wave is usually followed by a QRS complex, and the PR interval is typically not prolonged. Thus the P’P’ intervals do not vary by more than 50 ms unless an exit block from the focus of FAT is present. – AV block may be present during FAT and is due to decreased sympathetic tone or digitalis toxicity. – Tachycardia-induced ST segment depression and T wave inversion may occur and may persist for some time after the cessation of long-lasting FAT. – During MAT there are ≥3 distinct P’ waves of varying morphology in the same ECG lead; there is no dominant atrial pacemaker (difference from sinus rhythm with frequent premature atrial complexes and focal AT); AV conduction may be variable; and there is an isoelectric baseline with varying PP, PR, and RR intervals. Multiple P’ wave morphologies and variable P-R and R-R intervals may contribute to confusion of MAT and atrial fibrillation. The ventricular rate is usually 100–150 bpm but may be as high as 250 bpm. • Ambulatory (Holter) monitoring is very helpful in establishing the FAT diagnosis. • Exercise testing is frequently not useful because the sinus heart rate increases and the automatic focus is suppressed.

CONCOMITANT ORGAN DYSFUNCTION • COPD, pulmonary infection • Congestive heart failure

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Uncontrolled ventricular rate, hemodynamic instability, signs of myocardial ischemia, or cardiac decompensation • Cardiac consultation may be necessary.

CLASSIFICATIONS

Varies; depends on pathophysiologic characteristics or clinical presentation

TREATMENT PREOPERATIVE PREPARATION Premedications

• A combination of benzodiazepines and opioids will decrease anxiety and modulate sympathetic tone. • Anticholinergic agents may worsen AT. • Consider medications that decrease automaticity and AV conduction without decreasing cardiac output.

Special Concerns for Informed Consent Increased risk of cardiac complications INTRAOPERATIVE CARE Choice of Anesthesia

Depends on the surgical procedure. There is insufficient evidence to suggest that either general or regional anesthesia is more beneficial for patients with ATs. Monitors

• Standard ASA monitors including ECG with ST segment and T wave trends • Arterial catheter for cases of expected blood pressure instability or need for frequent blood gas evaluation (COPD) • Central venous catheter is optional, but if utilized, intracardiac stimulation should be minimized during catheter placement. • Pulmonary artery catheter may be used in cases of cardiomyopathy.

Induction/Airway Management

• Increased risk of hemodynamic instability due to cardiac depression caused by intravenous or inhalational anesthetics • Consider administration of higher doses of benzodiazepines and opioids to decrease sympathetic tone • Dexmedetomidine, an alpha-2 agonist, may be useful in decreasing the sympathetic tone and the heart rate, but the loading dose may cause significant hypotension. • Ketamine and pancuronium are relatively contraindicated. • Minimize the length of laryngoscopy or avoid laryngoscopy with the use of a laryngeal mask airway or intravenous sedation.

Maintenance

• Neither propofol nor volatile agents have significant electrophysiologic effects and are adequate maintenance agents. • Conservative fluid management in case of cardiomyopathy

Extubation/Emergence

• Balanced reversal of neuromuscular block, with slow administration

• Avoid sympathetic stimulation • Complications: – Hemodynamic instability, coronary ischemia – Tachycardia-induced cardiomyopathy

FOLLOW-UP BED ACUITY

Poorly controlled AT will dictate ICU care.

MEDICATIONS/LAB STUDIES/CONSULTS

• Rate control as indicated • Electrolytes, digoxin level, cardiac enzymes

COMPLICATIONS

• Hemodynamic instability, coronary ischemia • Tachycardia-induced cardiomyopathy

REFERENCES

1. Roberts-Thomson KC, Kistler PM, Kalman JM. Atrial tachycardia: Mechanisms, diagnosis and management. Curr Probl Cardiol. 2005;30:529–573. 2. McCord J, Borzak S. Multifocal atrial tachycardia. Chest. 1998;113:203–209. 3. Saoudi N, Cosio F, Waldo A, et al. A classification of atrial flutter and regular atrial tachycardia according to electrophysiological mechanisms and anatomic bases. Eur Heart J. 2001;22:1162–1182.

CODES ICD9 427.89 Other specified cardiac dysrhythmias ICD10 I47.1 Supraventricular tachycardia

CLINICAL PEARLS

• FAT usually occurs in young patients and may resolve spontaneously; however, failure to perceive an incessant FAT (e.g., in small children) can lead to a cardiomyopathy that may become irreversible if the tachycardia is not aggressively pharmacologically treated. • MAT usually occurs in elderly and seriously ill patients. It may resolve within days following successful management of the underlying disease. If management of the underlying disease is not successful, onset of MAT implies a poor prognosis. • Cardioversion has no effect on the sites of ectopy that produce automatic FAT and is not

effective in converting MAT to sinus rhythm. Radiofrequency catheter ablation may be curative.

AUTOLOGOUS BLOOD TRANSFUSION Andrew A. Klein, MD

BASICS DESCRIPTION

• Transfusion of the patient’s own blood or blood components back to them has the theoretical advantages of: – No risk of transmission of infection – No blood transfusion reaction – No graft versus host disease – No storage of blood required (except with preoperative autologous blood donation [PABD]) • There are 4 types of autologous blood transfusion: – Preoperative autologous blood donation – Intraoperative hemodilution – Cell salvage or saver – Postoperative blood collection and re-transfusion • Allogeneic transfusions are the “opposite” of autologous transfusions and involve giving a patient blood collected from another person and has been stored in the blood bank. • “You know what you’ve got inside you and therefore what you’re getting.”

PHYSIOLOGY PRINCIPLES

• Oxygen-carrying capacity: In a normal person breathing room air, arterial blood carries approximately 20 mL O2/100 mL; 19.7 mL combined with hemoglobin (Hb) and only 0.3

mL dissolved in plasma. Hemoglobin molecules within red blood cells contain iron that can bind reversibly to oxygen molecules to form oxyhemoglobin. Normal Hb is 13–16 g/dL in men and 12–16 g/dL in women. • Viscosity is the tendency of fluids to resist flow. Blood viscosity depends largely on hematocrit (increasing exponentially as hematocrit increases), red cell characteristics, and blood protein concentration. Increasing viscosity (from blood transfusion) leads to reduced flow, especially in vessels <0.3 mm in diameter. This causes an increase in resistance with a resultant increase in blood pressure (blood pressure is equal to cardiac output multiplied by resistance: BP = CO × R). • Transfusion, even of autologous blood, should be reserved for when it is needed, and local protocols should be followed. The ACC/AHA Guidelines recommend that blood is given when the Hb <6 g/dL; as this is described as lifesaving. They also state that transfusion in most postoperative patients with a Hb <7 g/dL is reasonable and that in select patients with critical end-organ ischemia, it may be necessary to transfuse at a Hb of 10 g/dL. • Preoperative autologous blood donation (PABD): 1–2 units of blood are collected from the patient 2–4 weeks before surgery. – The goal is to remove red blood cells and plasma, process it, and store it until the day of

surgery. The blood is not separated into components and is re-administered as whole blood. Thus, it contains some or all of the blood components needed by the patient. – Preoperative donation allows the patient time to recover and begin red cell regeneration, provided that iron stores are adequate. Thus, levels should be checked and iron supplementation administered if necessary. – Guidelines state that patients should be in good health to tolerate phlebotomy of around 450 mL and autologous blood collection should only be offered to those patients in whom there is a reasonable expectation that blood will be required. – Patients who would not normally require cross-matched blood (e.g., Group and Save only) should not be considered, unless there is a specific clinical reason. Direct patient requests should be discouraged after adequate explanation. – Contraindications include anemia (Hb <11 g/dL), current infection, no definite surgical date, severe cardiac, respiratory, or cerebrovascular disease, and pregnancy. – Autologous blood should be stored in a refrigerator at a controlled temperature between 2 and 8°C, with alarms set at 3–7°C, and physically separated from homologous blood stocks and cross-matched blood. This refrigerator should be equipped with a recorder and an alarm similar to those on other fridges used for blood storage. – The autologous label for each unit should include all necessary information for correct identification of the patient and should have a suitable adhesive for refrigerated storage. • Intraoperative hemodilution consists of blood collection immediately before surgery (usually after induction of anesthesia), followed by IV fluid replacement to prevent hypovolemia. Blood is then re-infused at the end of, or after, surgery. Blood is kept warm in the operating theatre (can be stored for up to 8 hours in blood collection [containing citrate] bags without refrigeration). – Popular in cardiac surgery before or immediately after commencing cardiopulmonary bypass – Usually acceptable to Jehovah’s Witnesses if blood is kept in continuous contact with the patient – Less metabolic derangements due to the shorter storage time; hyperkalemia does not develop in <24 hours but hemolysis can occur during blood removal if too small a line is used. – Hematocrit before blood removal should be >30%, and generally >36%. After blood removal, hematocrit should be >24%. • Cell salvage is the most common method of autologous blood transfusion. Blood lost during or immediately after surgery is suctioned and collected into a designated reservoir. Heparin is added to prevent clotting and is processed and transfused back to the patient. – May commonly be utilized in cardiac, vascular, and orthopedic surgery • Postoperative blood collection (most often after orthopedic surgery) and re-transfusion of unprocessed blood back to the patient. It has been used in cardiac and orthopedic surgery, as well as traumatic hemothorax. During total knee replacement, the surgery is most commonly performed with a tourniquet in place, and this is then deflated at the end of the procedure after a drain has been placed in the joint. This drain is then opened after 30–60 minutes, and the blood collects into a specifically designed collection reservoir (bellows) using vacuum suction (as opposed to wall suction). The collected blood is filtered before

being immediately transfused back to the patient; this is performed on an hourly basis. This system is low-cost, easy to perform, and with minimal side effects. Blood is defibrinogenated and thus does not require anticoagulation prior to transfusion; additionally, it is sterile. • Autologous platelet-rich plasma is collected from the patient intraoperatively via apheresis equipment. When used for cardiac surgery patients, it is removed prior to heparin administration and the onset of cardiopulmonary bypass. It is returned after heparin reversal. Studies have not shown improved benefit in regard to hemostasis and/or decreased need for transfusion.

PHYSIOLOGY/PATHOPHYSIOLOGY

• PABD can have disadvantages, problems, and/or challenges including: – Wastage of blood due to cancellation of surgery – Inability to utilize the blood for another patient, in the event that it is not given to the donor patient. A small number of autologous units are administered to other patients; however, due to the donor’s comorbidities, autologous units are often unsuitable for allogeneic donation. – The need for storage – Metabolic derangements still exist, such as hyperkalemia and loss of 2,3 DPG (related to length of storage) – Potential for administrative error – Blood must still be warmed during infusion to prevent hypothermia. – Donation may predispose to deterioration in medical condition (e.g., severe ischemic heart disease). – Contraindicated in patients with anemia – Unacceptable to Jehovah’s Witnesses – Not often practiced due to logistical reasons, particularly scheduling of surgery, collecting, and storing blood (different locations) – Does not guarantee that allogeneic blood will not be transfused – Vasovagal reactions during collection from hypotension and bradycardia – Increased cost compared to allogeneic blood units • Intraoperative hemodilution can have disadvantages including: – Hemodynamic instability: Removal of up to 500 mL of blood is possible; however, loss of volume may cause hypotension unless fluid is replaced immediately. – Precipitation of myocardial ischemia or worsening tissue oxygenation from acute anemia – Need for wide-bore vascular access; central venous may be necessary if the arm IV is insufficient or unreliable. – Blood storage time is limited to a few hours. It should not be stored in the blood fridge, but kept in the patient’s immediate vicinity and transfused within 8 hours. • Cell salvage can have disadvantages including: – Loss of plasma containing clotting factors and platelets leading to coagulopathy and bleeding. This is only relevant after at least 50% of a patient’s blood volume has been processed. – Requires “enough” blood loss in order to prepare a unit • Postoperative blood collection can have disadvantages including:

– Risks of fluid overload with rapid re-infusion – Clotting of blood in re-transfusion bag if not administered to patient immediately after filtration • Direct re-infusion of shed mediastinal blood from postoperative chest tube drainage is not recommended as a means of blood conservation and may cause harm (Level B evidence).

PERIOPERATIVE RELEVANCE

• Autologous transfusion can optimize or increase Hb while reducing the risk and amount of allogeneic blood transfusion. • Allogeneic blood is strongly associated with increased risk of death (1)[B] and complications, including postoperative infection (2)[A], cancer recurrence, acute lung injury (TRALI) (3)[B], and increased length of stay in the intensive care unit and hospital. Risk correlates with the number of units of allogeneic blood transfused and length of time that the blood is stored (4)[B]. These risks are NOT associated with autologous transfusion. • Needs advance planning and preparation before surgery • Discuss with the surgeon and patient

REFERENCES

1. Karkouti K, Wijeysundera DN, Yau TM, et al. The independent association of massive blood loss with mortality in cardiac surgery. Transfusion. 2004;44:1453–1462. 2. Duffy G, Neal KR. Differences in post-operative infection rates between patients receiving autologous and allogenic blood transfusion: A meta-analysis of published randomized and nonrandomized studies. Transfusion Med. 1996;6:325–328. 3. Brander L, Reil A, Bux J, et al. Severe transfusion-related acute lung injury. Anesth Analg. 2005;101:499–501. 4. Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med. 2008;358:1229–1239. See Also (Topic, Algorithm, Electronic Media Element) • Cell salvage • Blood transfusions • Transfusion-related infections • Blood substitutes

CLINICAL PEARLS

• Autologous blood transfusion is commonly considered in coronary artery bypass, major vascular surgery, primary and revision hip or total knee replacements, hepatic resections, radical prostatectomies, and major spine surgery with instrumentation. • Directed donation describes blood donated by a friend or family member for a designated patient. This may be used when the patient’s health or baseline hemoglobin may not be suitable for autologous donation. Drawbacks, however, are that it is not as safe as the patient’s own blood and is handled as an autologous donation.

AUTONOMIC HYPERREFLEXIA John F. Bebawy, MD Antoun Koht, MD

BASICS DESCRIPTION

• Autonomic hyperreflexia (AH) is a syndrome characterized by profound and imbalanced reflex sympathetic discharge occurring in patients with spinal cord injury (SCI) at or above the T6 level. – Inciting stimulus ranges from innocuous to noxious. – Unchecked sympathetic discharge occurs below the level of injury in response to a stimulus also below the level of injury. – Compensatory hemodynamic responses occur above the level of injury. – Also known as “autonomic dysreflexia” • Patients with SCI commonly present to the operating room for urologic and other lower extremity procedures (e.g., decubitus ulcers) that can elicit AH. EPIDEMIOLOGY Prevalence

• Associated with the incidence of SCI at or above the T6 level; in the US, there are 12,000 new cases of SCI annually. • Pregnant women with SCI at or above the T6 level: 2/3rd can experience AH during labor. Prevalence

• 48–90% of patients with SCI at or above the T6 level • Males:females 4:1

Morbidity

Primarily due to uncontrolled hypertension leading to myocardial infarction, cerebral hemorrhage, seizures Mortality

Rare as a direct result of AH

ETIOLOGY/RISK FACTORS

Any stimulation below the level of SCI. Most commonly: • Bladder distension • Bowel distension • Surgery • Pressure sores • Urinary tract infection (UTI)

• Cholelithiasis • Sexual intercourse

PHYSIOLOGY/PATHOPHYSIOLOGY

• AH can be seen after the initial spinal shock phase of SCI, when autonomic reflexes return. • Injury at or above the T6 level is above major splanchnic sympathetic outflow (T6 to L2). • Sensory input below the level of injury is transmitted via peripheral nerves to the spinothalamic tract and posterior columns of the spinal cord, and activates sympathetic neurons. • However, normal, descending inhibitory outflow is blocked at the level of injury; this leads to unopposed and abnormal sympathetic discharge and elevated blood pressure (due to unopposed vasoconstriction). • Brainstem and carotid baroreceptor reflexes above the level of injury attempt to compensate for the elevation in blood pressure (below the level of injury) by increasing parasympathetic discharge to the heart via the vagus nerve; this leads to bradycardia and compensatory vasodilation above the level of injury.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Despite the possible loss of sensation, anesthesia for procedures below the level of SCI is advisable to prevent AH. – General anesthesia and spinal anesthesia are preferred methods. – Epidural anesthesia may also be beneficial, but to a lesser extent due to reduced block density and sacral nerve sparing. • Be prepared to treat manifestations of AH (e.g., with short-acting and direct-acting antihypertensives).

PREOPERATIVE ASSESSMENT SYMPTOMS

Headache, blurred vision, nasal congestion, chest pain, anxiety History

• Ascertain the level, age, completeness, and stability of the SCI. • In cervical injury, assess if spinal fixation has been performed. • Frequency and inciting events for AH (e.g., urinary catheterization, bowel distension, etc.)

Signs/Physical Exam

• Asymptomatic in between episodes of AH • During an episode of AH: – Below the level of SCI: Elevated blood pressure, cool to touch, piloerection – Above the level of SCI: Flushing and sweating, bradycardia, cardiac arrhythmias (atrial fibrillation, premature ventricular contractions, AV conduction abnormalities)

TREATMENT HISTORY

• Prophylactic efforts include the removal of inciting stimulus:

– Bladder catheterization, fecal disimpaction, etc. • Sitting patient up from the supine position, legs down

MEDICATIONS

No specific routine medications

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

Depend upon the surgical procedure and other patient comorbid conditions CONCOMITANT ORGAN DYSFUNCTION • Decubitus ulcers • Contractures and deconditioning • Frequent UTIs • Pulmonary impairment

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Acute episodes of AH should trigger a search for, and removal of, inciting stimulus, and/or postponement of nonemergent surgical interventions. • Emergent surgical intervention during an AH episode should be performed under spinal or general anesthesia.

CLASSIFICATIONS None

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics as appropriate • Vasodilators if acutely hypertensive

Special Concerns for Informed Consent

• Cases planned to involve sedation should include the caveat that a spinal or general anesthetic may be used to treat an acute AH episode. • Morbidity of an acute AH episode should be reviewed, especially for lower body surgery.

INTRAOPERATIVE CARE Choice of Anesthesia

• Spinal anesthesia may be preferred since it blocks descending spinal cord reflexes directly (1)[C]. • General anesthesia, at adequate levels, can inhibit reflex spinal sympathetic discharge. • Epidural anesthesia may be used but could be less effective in severe AH cases.

Monitors

• Standard ASA monitors • Consider an arterial line if the patient is at high risk (e.g., lower body surgery, prolonged surgery) for, or has had a confirmed AH episode.

Induction/Airway Management

• Awake fiberoptic intubation or other alternative airway devices may be preferred in patients with previous cervical fusion and limited neck mobility, or in those patients with an unstable cervical spine. • Induction drugs should not aggravate pre-existing hypertension, nor should they cause excessive hypotension, since vascular tone below the level of SCI is lower at baseline (but higher during an acute AH episode). • Avoid succinylcholine; a proliferation of extrajunctional receptors due to disuse can result in massive amounts of potassium extravasating from the muscle with the use of a depolarizing muscle relaxant.

Maintenance

• General anesthesia should be maintained at adequate levels to inhibit reflex sympathetic discharge. • Epidural catheters should be appropriately redosed with local anesthetics or have an infusion started in order to maintain adequate block density. • An AH episode should be immediately treated with: – Direct-acting vasodilators: Calcium channel blockers, nitrates, hydralazine – Beta-blockers are second-line because of their potential to cause unopposed alpha-related vasoconstriction. – Central-acting vasodilators (e.g., clonidine) may be less effective.

Extubation/Emergence

• Short-acting antihypertensives should be immediately available to treat emergence-related hypertension. • Extubation of patients with cervical fusion should be performed when the patient is oxygenating and ventilating independently and following commands.

FOLLOW-UP BED ACUITY

Following an episode of AH, monitor blood pressure and heart rate in a monitored setting for at least 2 hours. MEDICATIONS/LAB STUDIES/ CONSULTS

• If the patient had an intraoperative episode of AH, antihypertensives should be continued, as appropriate • If myocardial ischemia is suspected: – Electrocardiogram

– Troponin levels – Opioids, nitrates, oxygen, vasopressors, as needed – Cardiology consultation

COMPLICATIONS

Profound sympathetic discharge can result in (2): • Cardiac ischemia • Cerebral edema • Cerebral hemorrhage • Renal failure • Ophthalmic/retinal disease • Pulmonary edema

REFERENCES

1. Khastgir J, Drake MJ, Abrams P. Recognition and effective management of autonomic dysreflexia in spinal cord injuries. Expert Opin Pharmacother. 2007;8(7):945–956. 2. Kirshblum SC, Priebe MM, Ho CH, et al. Spinal cord injury medicine: Rehabilitation phase after acute spinal cord injury. Arch Phys Med Rehabil. 2007;88(3 Suppl 1):S62–S70.

ADDITIONAL READING

• Mallory B.Autonomic dysfunction in spinal cord disease. In: Lin VW, Cardenas DD, Cutter NC, et al., eds. Spinal cord medicine: Principles and practice, 1st ed. New York: Demos, 2003.

See Also (Topic, Algorithm, Electronic Media Element) • Spinal shock • Autonomic nervous system

CODES ICD9 337.3 Autonomic dysreflexia ICD10

G90.4 Autonomic dysreflexia

CLINICAL PEARLS

• Autonomic hyperreflexia (AH) is a syndrome characterized by profound and imbalanced reflex sympathetic discharge occurring in patients with spinal cord injury (SCI) at or above the T6 level. • An AH episode is characterized by any of the following: Headache, blurred vision, nasal congestion, chest pain, anxiety, elevated blood pressure, bradycardia, flushing and sweating

above level of SCI, piloerection, or cardiac arrhythmias. • Treatment of an AH episode involves the administration of antihypertensives, removal of the inciting stimulus (bladder catheterization, fecal disimpaction, etc.), sitting the patient up from the supine position, placing the legs down, and loosening of any tight clothing. • For all lower body surgeries, even in the absence of sensation, the provision of an anesthetic should be considered.

AUTONOMIC NERVOUS SYSTEM Anthony H. Guarino, MD

BASICS DESCRIPTION

• The autonomic nervous system (ANS) regulates individual organ function and homeostasis and, unlike the somatic nervous system, is not under voluntary control. It comprises the: – Sympathetic system – Parasympathetic system – Enteric nervous system: Not frequently discussed; a meshwork of nerve fibers that innervate the GI tract, pancreas, and gallbladder. • The sympathetic nervous system can be therapeutically blocked via neuraxial techniques (spinal and epidural), localized paravertebral ganglia blocks, and regional IV sympatholytic injections. PHYSIOLOGY PRINCIPLES

• Sympathetic nervous system (SNS): The SNS is continuously maintaining homeostasis in the body. When stress is encountered there is increased activity resulting in the increased release of catecholamines (“fight or flight”). – Preganglionic neurons originate in the thoracic and lumbar spinal cord. Their axons project to a paravertebral sympathetic trunk (or chain) that extends from C2 to the coccyx. Most preganglionic neurons synapse with postganglionic neurons within the trunk. Some preganglionic neurons travel to other ganglia outside of the sympathetic chain and synapse there. – Postganglionic neurons from the sympathetic trunk (as well as outside ganglia) travel to the target organ. – Neurotransmitters: Preganglion and postganglion synapses: Acetylcholine Postganglion and target organ: Norepinephrine. An exception is sweat glands that utilize acetylcholine. – Effects on organs: Eyes: Dilates pupils Heart: Tachycardia and increased force of contractions (increases systolic blood pressure) Vasculature: Increases the tone (vasoconstriction) and hence diastolic blood pressure Pulmonary: Dilates bronchioles Gastrointestinal: Inhibits peristalsis Renal: Increases renin secretion which retains sodium and water Penis: Promotes ejaculation • Parasympathetic nervous system (PNS): The PNS works complementary to the ANS in maintaining homeostasis in the body. It is generally thought to guide vegetative functions (“rest and digest”).

– Preganglion neurons originate in the medulla (cranial nerves III, VII, IX, and X) as well as the cervical and sacral spinal cord. Their axons project to ganglia close to the target organ where they synapse with postganglionic neurons; they have a longer course compared to preganglionic sympathetic neurons. Of note, ∼75% of the parasympathetics travel with the vagus nerve. – Postganglionic neurons have a short distance that they travel to the target organ. – Neurotransmitters: Preganglion to postganglion synapses: Acetylcholine Postganglion to target organ synapses: Acetylcholine – Effects on organs: Eyes: Constricts pupils Heart: Decreases the heart rate Vasculature: Decreases tone (vasodilation) Pulmonary: Constricts bronchioles Gastrointestinal: Promotes peristalsis Penis: Promotes erections • Adrenal medulla: Develops tandemly in utero with the SNS and acts as a modified sympathetic ganglion. Synapses occur between preganglionic and postganglionic neurons within it, but the postganglionic neurons do not leave the medulla; instead they directly release norepinephrine and epinephrine into the blood.

DISEASE/PATHOPHYSIOLOGY

• Complex regional pain syndrome I and II is a chronic neuropathic pain disorder. Although the exact pathophysiology remains unknown, manifestations are secondary to ANS dysfunction. CRPS I and II are characterized by pain in a nondermatomal pattern. Signs and symptoms of neuropathic pain include intense burning pain, hyperalgesia, allodynia, local edema, sweating, skin color changes, and temperature disturbances in the affected extremity. • Peripheral vascular disease refers to arterial obstruction outside the heart. It can cause ischemia and is believed to be associated with dysfunction of the ANS. • Raynaud’s disease is an exaggerated and reversible vasospasm of digital arteries in response to cold or stress. The etiology is believed to be secondary to ANS dysfunction.

PERIOPERATIVE RELEVANCE

• Propofol, at clinically relevant concentrations for sedation, does not alter central sympathetic outflow at the spinal cord level. However, at deeper levels of sedation and induction doses, it can depress central sympathetic activity and is likely to lead to hypotension (decreases preload, afterload, and contractility). • Ketamine causes direct, dose-dependent stimulation of the CNS that leads to increased SNS outflow. Consequently, cardiovascular effects resemble SNS stimulation: Increases in systemic and pulmonary blood pressures, heart rate, cardiac output, cardiac work, and myocardial oxygen requirements. Systemic vascular resistance and LV end diastolic pressure are normally unchanged. In the critically ill, it has a negative inotropic effect. • Etomidate maintains hemodynamic stability through preservation of both sympathetic outflow and autonomic reflexes.

• Opioids generally have a dose-dependent sympatholytic effect. • Benzodiazepines can influence autonomic neurocardiac regulation, probably through their interaction with the gamma-aminobutyric acid A-receptor (GABAA) chloride ion channel

complex. They act in a biphasic manner: Initially causing a reduction in central vagal tone followed by decreasing the cardiac pacemaker directly. Induction doses can reduce blood pressure but not to the same degree as propofol. • Anticholinesterases enhance PNS activity and will cause bradycardia, hypotension, hypersecretion, bronchoconstriction, GI tract hypermotility, and decrease intraocular pressure. • Anticholinergics inhibit parasympathetic nerve impulses by selectively blocking acetylcholine receptor binding at nerve junctions. • Inhaled volatile anesthetics generally suppress the ANS components in a dose-dependent manner. • Neuraxial blocks: Local anesthetics injected into the epidural or intrathecal space produce a differential blockade. Nerve fibers have different sensitivities due to their location in the spinal cord, diameter, and the presence or absence of myelin. Sympathetic nerve fibers are blocked first, and are usually followed by pain, sensory, and motor nerves. • Sympathetic blocks: Performed to interrupt nociceptive pathways as well as vasomotor, sudomotor, and visceromotor nerves. Low concentrations of local anesthetics block small myelinated A-delta and unmyelinated C fibers with a minimal effect on other parts of the peripheral nerves. They may be performed as a diagnostic tool to determine if sympathetic input is a contributor to the pain state. Thus, they help guide decisions on whether a more permanent intervention would be helpful (e.g., neurolysis or surgery). • Horner syndrome is seen with interscalene brachial plexus blocks, due to the nerve’s proximity. Manifests as ptosis, miosis, enophthalmos, conjunctival injection, nasal congestion, and facial anhidrosis. GRAPHS/FIGURES

FIGURE 1. Sympathetic nervous system. Preganglionic neurons originate in the thoracic and lumbar spinal cord and synpase with postganglionic neurons in the paravertebral sympathetic trunk.

FIGURE 2. Parasympathetic nervous system. Preganglionic neurons originate in the medulla and cervical and sacral spinal cord and then synapse with postganglionic neurons near the target organ.

REFERENCES

1. Marx JL. New information about the development of the autonomic system. Science. 1979;206(4417):434–437. 2. Burnstock G. Autonomic innervation and transmission. Br Med Bull. 1979;35(3):255–262. 3. Burnstock G. Review lecture: Neurotransmitters and trophic factors in the autonomic nervous system. J Physiol. 1981;313:1–35. 4. Burnstock G. The changing face of autonomic neurotransmission. Acta Physiol Scand. 1986;126(1):67–91. 5. Hirst GD, Choate JK, Cousins HM, et al. Transmission by post-ganglionic axons of the autonomic nervous system: The importance of the specialized neuroeffector junction. Neuroscience. 1996;73(1):7–23.

ADDITIONAL READING

• http://www.sciencedaily.com/articles/s/sympathetic_nervous_system.htm • http://www.ehs.net/2231/pdf/autonomic.pdf See Also (Topic, Algorithm, Electronic Media Element) • Complex regional pain syndrome I • Complex regional pain syndrome II • Epidural • Raynaud phenomenon

CLINICAL PEARLS

• Sympathetic blocks can aid an anesthetic as well as reduce pain during postoperative care. • Autonomics affect every organ system in some manner or form.

AWAKE CRANIOTOMY R. Alexander Schlichter, MD

BASICS DESCRIPTION General

• Evidence of trephinated skulls dates back to prehistoric times. The modern era of awake craniotomies began with cocaine local anesthesia in 1886; sedation was added in the 1930s. • Today, awake craniotomies are performed when patients have tumors or epileptic foci near eloquent areas of the brain (Broca, Wernicke). • Variations in anesthetic technique depend upon the patient as well as the surgeon’s preference. During cognitive testing and tumor resection, the patient must be awake. However, line and block placement, craniotomy, bone flap removal, as well as dural closure can be performed with an adequate level of sedation versus general anesthesia (“asleepawake-asleep” technique). Position

• In “asleep-awake-asleep” techniques, the patient is positioned after induction, whereas with sedation the patient’s comfort is assessed before deeper levels are administered. • Supine, with a bump under the left side so that the patient is facing the anesthesiologist. • The patient’s left arm is folded over the patient and the right arm is abducted out. Pressure points are padded. • The patient is placed in a Mayfield frame. In sedated patients, the scalp block is first tested and additional local anesthetic is added at pin sites. • The patient is draped such that there is a window for the patient to communicate with the anesthesiologist. This also allows emergent access to the airway. • For the rare right-sided awake craniotomy, the above positioning is reversed.

Incision

Temporal incision: Temporalis flap, Burr hole, bone flap and then excision of the dura Approximate Time

3–5 hours. The anesthesia and surgical preparatory time is longer than it is for a standard craniotomy. EBL Expected

300–500 mL. More bleeding can occur, so adequate venous access and blood products should be available. Hospital Stay

3–5 days for uncomplicated surgeries

Special Equipment for Surgery

• Mayfield frame • Stealth/MRI • Surgical microscope • Special surgical drape for access to the patient • Speech mapping electrodes and neuromonitoring personnel • Ice cold saline in case of seizure

EPIDEMIOLOGY Incidence

• The incidence of these lesions being removed under awake craniotomy is neurosurgeon- and institution-driven, and therefore varies from center to center. • Improvements in anesthetic techniques have resulted in an increased incidence of awake craniotomies being performed.

Prevalence

• Dependent on type of lesion and location • Most epileptic syndromes are treated medically. The prevalence of operable epilepsy is institutionally dependent.

Morbidity

Low. Patient selection for awake craniotomies provides a healthier cohort. Tumors are also usually smaller but in strategic brain tissue. Mortality Low

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The choice of sedation and analgesic drugs may vary by institution; the ideal drug for the procedure should be quick in onset, short in duration, and easy to titrate. • The choice between deep sedation versus “asleep-awake-asleep” technique depends upon the patient’s, as well as the surgeon’s preference. Sedation is possible because a scalp block is capable of providing adequate anesthesia for scalp incision/craniotomy and the brain has no intrinsic nociception. Oversedation can lead to obstruction, apnea, loss of airway, or hypoventilation with resultant increases in CBF and/or ICP. • Personal reassurance and communication are powerful tools in keeping patients calm. Consider meeting the patient in a preoperative visit, the night before, or having a phone discussion prior to the day of surgery. • Seizure, stroke, and oversedation can occur quickly. Emergency airway drugs and equipment must be readily available.

PREOPERATIVE ASSESSMENT SYMPTOMS

Cognitive speech dysfunction, either expressive (Broca) or receptive (Wernicke) History

• History of cognitive speech dysfunction, seizures. • The tumor may be an incidental finding on brain imaging for an unrelated complaint. • Mental capacity, claustrophobia, anxiety, drug and alcohol abuse, sleep apnea, acid reflux, and BMI need to be assessed. Signs/Physical Exam

• Full neurologic exam including speech • Auscultation of heart and lungs • Airway exam

MEDICATIONS

• Dexamethasone decreases vasogenic tumor edema. • Anticonvulsants (phenytoin, levetiracetam)

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC, Type and Screen • Chemistry panel, coagulation panel • Head CT, MRI, functional MRI (fMRI)

CONCOMITANT ORGAN DYSFUNCTION

Most patients are relatively healthy from a cardiovascular profile. Most complain of headaches, seizures, or cognitive speech dysfunction.

TREATMENT PREOPERATIVE PREPARATION Premedications

• A dexmedetomidine bolus should be followed by an infusion. • When sedation is utilized, a small dose of midazolam may be considered prior to line and Foley catheter placement. Low-dose remifentanil infusion may be started prior to the scalp block. • Antiemetic prophylaxis should be administered with non-sedating drugs such as 5-HT3A and dexamethasone (also given to treat cerebral edema). Dexamethasone should be slowly infused in awake patients as it can cause severe rectal itching and burning. • Antiepileptic loading • Anticholinergics should be avoided unless necessary. Patients may complain of dry mouth during cognitive testing if used.

Special Concerns for Informed Consent

• The patient must be counseled that they will be awake during significant parts of the

surgery. Emphasize that open communication with the anesthesiologist is always possible. • Risk of seizure and intubation is possible. • Blood consents for possible transfusion are needed.

Antibiotics/Common Organisms

Gram-positive coverage for skin flora (cephalosporin, vancomycin for allergies) INTRAOPERATIVE CARE Choice of Anesthesia

• Sedation involves the administration of IV sedative and analgesic medications (most commonly dexmedetomidine, remifentanil, and propofol). Propofol and remifentanil alone can be used, but are associated with deeper sedation, hypercarbia, and airway problems. Neuroleptic analgesia with droperidol and an opioid has been associated with dysphoria, oversedation, and hypotension. • “Asleep-awake-asleep" is often performed with a combination of dexmedetomidine, remifentanil, and propofol at higher doses than sedation and then resumed after tumor excision.

Monitors

• Standard ASA monitors • Arterial line for beat-to-beat monitoring, labs • 2 large-bore IVs (14–18) for rapid resuscitation and blood transfusion • Central venous access is only necessary in patients with poor venous access. Awake placement can be stressful for the patient. • Foley catheter with urometer. In awake patients, especially in males, urethral lidocaine can ease discomfort of placement and maintenance. • Bispectral analysis can help guide the depth of anesthesia during GA or deep sedation. • Neuromonitoring with speech mapping electrodes and appropriate personnel

Induction/Airway Management

• Scalp block: Usually done while the patient is lightly sedated (and before the patient is induced for the “asleep-awake-asleep”) to monitor for local anesthetic toxicity. Often performed with 0.5% bupivacaine or ropivacaine. The surgeon can infiltrate pin sites, incision sites, and dura with 1% lidocaine. • Sedation: Oxygen delivery via nasal cannula, facemask, or non-rebreather facemask • “Asleep-awake-asleep": An LMA is often placed with either spontaneous ventilation or controlled ventilation. Controlled ventilation is associated with lower CO2 levels.

Alternatively, a sphenopalatine block with bilateral placement of nasal trumpets can allow spontaneous ventilation and a lighter depth of anesthesia than an LMA. The nasal trumpets can be left in place, allowing the patient to phonate during testing. Obstruction is still possible.

Maintenance

• Sedation: Dexmedetomidine 1 mcg/kg over 10 minutes followed by an infusion of 0.2–0.5 mcg/kg/hr. Remifentanil 0.01–0.05 mcg/kg/min. For sedation only, propofol should be

used sparingly if at all. Patients may find manipulation of the dura, in particular traction, painful. • “Asleep-awake-asleep": Dexmedetomidine 1 mcg/kg over 10 minutes followed by an infusion of 0.2–0.5 mcg/kg/hr. Remifentanil 0.01–0.05 mcg/kg/min and propofol at 40–80 mcg/kg/min. Titrate to respiratory rate, and ETCO2. If using an LMA, control CO2 with pressure support ventilation. Turn propofol off for emergence to “awake” portion. • Brain relaxation: Mannitol and/or loop diuretic for diuresis. Diuresis can offset reductions in brain relaxation that can result form higher CO2 tensions.

• Cognitive testing: The patient is awake, responsive, and able to participate in testing. If the patient is under general anesthesia with an LMA or ETT, a smooth emergence should be the goal to avoid coughing, laryngospasm, bucking, or delirium. Testing consists of a series of neurologic tests: Counting, ABC’s, names, word association, pictures, and simple motor commands. During these simple tests, the neurosurgeon electrically stimulates portions of the brain to determine if it is safe to excise. • Tumor excision: After testing, the patient remains conversant as the tumor is excised to assure that eloquent tissue is not removed. • Seizure precautions: Because the brain is being directly stimulated, the risk of seizure is significant. Anticonvulsants should be loaded at the beginning of the case. Ice cold saline should be available to the surgeon to flood the field. Emergency airway drugs and equipment should be immediately available. • After tumor removal, the patient can be placed under heavy sedation or GA until the end of the procedure with appropriate airway protection in place.

Extubation/Emergence

• “Asleep-awake-asleep": Medications should be discontinued and the LMA removed when the patient is breathing and following commands. Patients with nasal airways can have them removed when they are awake. • Neurologic exam should be performed to confirm that no changes in neurocognitive function occurred during closure.

POSTOPERATIVE CARE BED ACUITY

ICU: Quick discharge if the patient has no neurologic changes ANALGESIA

• Pain is typically mild since the residual scalp block and dexmedetomidine can provide relief. • Short-acting IV opioids and oral opioids • Oral, rectal, and IV acetaminophen

COMPLICATIONS

• Cerebral edema can occur postoperatively. Any changes in neurologic exam need to be examined and the patient should be sent to neuroimaging. • Postoperative seizures (1–11% incidence) can be treated with appropriate anticonvulsants.

Continue the patient’s regular medication regimen. • Postoperative nausea and vomiting should be treated with non-sedating antiemetics.

PROGNOSIS

Good: Residual seizure activity or regrowth of tumor may require additional surgery.

REFERENCES

1. Bonhomme V, Franssen C, Hans P, et al. Awake craniotomy. Eur J Anesthesiol. 2009;26(11):906–912.

2. Bulsara KR, Johnson J, Villavicencio AT, et al. Improvements in brain tumor surgery: The modern history of awake craniotomies. Neurosurg Focus. 2005;18(4):e5. 3. Mack PF, Perrine K, Kobylarz E, et al. Dexmeditomidine and neurocognitive testing. J Neurosurg Anesthesiol. 2004;16:20–25. 4. Sarang A, Dinsmore J. Anaesthesia for awake craniotomy—evolution of a technique that facilitates awake neurological testing. BJA. 2003;90:161–165. See Also (Topic, Algorithm, Electronic Media Element) • Seizure disorder

CLINICAL PEARLS

• Patient refusal is a contraindication to an awake craniotomy. Patients with drug or alcohol abuse, obesity, mental retardation, anxiety, claustrophobia, sleep apnea, and gastroesophageal reflux should be scrutinized. • Communication and reassurance are paramount in keeping the patient calm and cooperative. • Adequate scalp block and additional local anesthetic in the field can improve success. • Alpha-2 agonists (dexmedetomidine) have been shown to improve sedation with less respiratory depression. • Seizure and loss of airway are a constant risk. Have airway drugs and equipment immediately available.

AWARENESS UNDER ANESTHESIA Dave Nisha Davendra, PharmD, DO Stephen P. Winikoff, MD

BASICS DESCRIPTION

• The term “awareness” during anesthesia implies that during a period of intended general anesthesia, the brain is aroused by stimuli that are stored in memory for future explicit recall. • The term “awake paralysis” is also included as an anesthesia awareness claim and refers to errors in the administration of neuromuscular blocking agents, resulting in paralysis of the unanesthetized patient. • Despite the infrequent occurrence, awareness is of significant concern to patients and is associated with significant adverse psychological sequelae. – Closed Claims Data identified 2 main causes of awareness: – Light anesthesia (“not enough") – Anesthetic delivery problems EPIDEMIOLOGY Prevalence

• Awareness during anesthesia may affect as many as 60,000 adults each year in the US. • Explicit recall is estimated to occur in 0.13% of patients (2). • Awareness with surgical procedures: – Trauma surgeries: 11–43% – Cardiac surgeries: 1.5% – Obstetric emergencies: 0.4% • Children have an increased incidence of 0.6–2.7%. • Awareness accounts for 2% of all claims in the Closed Claims database.

Prevalence

The majority of patients in the Closed Claims database are female, ASA class I–II, <60 years of age, and had elective surgery. Morbidity

• Postoperative sequelae that may persist for varying durations (33–69%): – Sleep disturbances including nightmares – Prone to daytime anxiety and panic attacks, and in the worst case, post-traumatic stress disorder (PTSD). 10–25% of patients who experience PTSD will not recover and will require treatment. – Avoidance of future medical care including any future anesthetic exposure • Patients, who experience the inability to move or feelings such as helplessness, have a

significant increase in the persistence of late psychological sequelae such as PTSD.

ETIOLOGY/RISK FACTORS

• Light anesthesia increases the risk for awareness. However, in certain patient populations, the administration of even small doses of anesthetic agents can result in deleterious hemodynamic consequences. – Limited cardiac reserve: Cardiac tamponade, coronary artery disease – Hypovolemia: Sepsis, trauma – Cesarean sections: Attempts to reduce uterine relaxation, fetal hazard, and hypotension can result in the administration of low concentrations of volatile anesthetics and the avoidance of benzodiazepines. – Cardiopulmonary bypass: Low concentrations of volatile agents and high-dose opioids are often administered to preserve hemodynamics. Because hypothermia while on pump can “provide MAC,” volatile anesthetics may be discontinued. • Anesthetic delivery problems. – Malfunctioning machines will disrupt the administration of anesthesia. Vaporizer and circuit leaks prevent administration of full doses of anesthetic agents to the patient. – Drug administration errors increase the risk of awareness. Accidental administration of muscle relaxant to an awake/conscious patient will cause awareness. • Reliance of nitrous, opioids, or muscle relaxants for anesthesia increases the risk of awareness. Volatile anesthetics are markedly more effective in producing amnesia. Use of neuromuscular blocking agents will mask physical signs of light anesthesia. • Premature discontinuation of anesthetics in attempts to awaken the patient more quickly increases the risk of awareness at the end of the surgical case. • Difficult intubations may entail repeated attempts to secure the airway, and supplemental agents may not have been administered. • Populations with increased anesthetic requirements may be underdosed when normal concentrations of anesthetic agents are administered. They include: – Pediatric patients – Chronic alcohol abusers – Opioid and cocaine abusers – Polypharmacy: Cytochrome P450 induction will enhance drug metabolism. • Patients on beta-blockers and calcium channel blockers can have their physiologic response to inadequate anesthesia masked. • Previous history of awareness under anesthesia can be an indication of increased risk for future awareness.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Interactions between analgesics and hypnotics are fundamental in the depth of anesthesia and physiology of awareness. – Hypnotic drugs are capable of producing CNS depression. – The net effect of analgesics and hypnotics is to increase the depth of anesthesia and decrease the probability of responsiveness. – The use of systemic analgesics and local anesthetics attenuates surgical stimulation before reaching the cortical level and causing awareness.

• Awareness is the postoperative recall of events occurring during general anesthesia. A spectrum of cognitive activity, including awareness with, or without, explicit memory, and unconscious awareness with implicit memory have been reported during the administration of drugs that are intended to induce and maintain general anesthesia. – Explicit memory is the conscious recollection of previous experiences. – Implicit memory is changes in performance or behavior that are produced by previous experiences but without any conscious recollection of those experiences. • Perceptions of awareness are variable: – Most common: Sounds, conversations, sensation of paralysis, anxiety, helplessness, pain, and panic – Least common: Visual perception, intubation, and feeling the operation without pain • Physical and physiologic responses have been reported that may indicate perception of painful stimulation whether conscious or unconscious. – Purposeful movement indicates motor response to awareness and surgical stimuli. – Rate and volume of ventilation in spontaneously breathing subjects, as well as heart rate and blood pressure, will increase indicating a physiologic response to awareness.

PREVENTATIVE MEASURES

• The incidence of awareness has decreased substantially over recent decades with improved appreciation of the complications and its morbidity as well as understanding of risk factors and causes. • Preoperative measures include patient and equipment assessment: – Review patient medical records for previous occurrences of awareness or potential risk factors. – Interview the patient to assess the level of anxiety and previous experience with anesthesia. – Inform high-risk patient of the possibility of intraoperative awareness, consent, and reassure the patient, as appropriate. – Conduct a preoperative checklist-based anesthesia machine and equipment check to ensure that the desired anesthetic drugs and dosages will be delivered. These procedures should be extended to include proper functioning of intravenous access, infusion pumps, and their connections. • Intraoperative measures include the adequate use of medications and monitors. – Amnestic agents should be strongly considered in anticipation or the possibility of a patient in whom light anesthesia is required (benzodiazepines, scopolamine). – Adequate doses of induction agents should be administered (also allow an adequate amount of time for onset). In rapid-sequence intubations, consider more than just a “sleep dose” of intravenous induction agents. – Difficult intubation (anticipated or unexpected) can require supplemental doses of an induction agent. – Volatile agents should be maintained at least at 0.8–1.0 MAC; monitor the end-tidal concentrations. – Muscle relaxant use should be minimized if not necessary for the surgical procedure since movement is the best indicator of light anesthesia. – Nitrous oxide and opioid anesthesia should be supplemented with a potent volatile agent

to decrease the high incidence of awareness. – Suspected inadequate anesthesia should be immediately addressed with deepening of the anesthetic and a benzodiazepine. – A bispectral index (BIS) is a processed electroencephalogram that provides a single dimensionless number, which ranges from 0 (equivalent to EEG silence) to 100 (equivalent to fully awake and alert). Values of 65–85 have been advocated as a measure of sedation, whereas values of 40–65 have been recommended for general anesthesia. The FDA states that the use of BIS monitoring to guide anesthetic administration may be associated with a reduction in the incidence of awareness with recall in adults during general anesthesia and sedation. However, studies have shown that awareness can occur at a BIS value <65, so the standard of care of this monitoring technique is equivocal. – Modulate operating room behavior. Patients tend to remember auditory perceptions.

PREOPERATIVE ASSESSMENT Conduct a postoperative interview with the modified Brice Questionnaire. • What was the last thing you remembered before going to sleep? • What was the last thing you remembered on waking? • Do you remember anything between going to sleep and waking? • While you were sleeping during the operation, did you dream?

TREATMENT • A discussion with the patient should take place to obtain a detailed account of the patient’s experience. • An occurrence report regarding the event should be completed for the purpose of quality management. • Apologize to the patient, and offer counseling or psychological support to the patient. • Notify the patient’s surgeon, nurse, and other key personnel about the incident and interview. • Patient should be informed of the Anesthesia Awareness Registry and encouraged to join the registry by calling (206) 616-2669 and request a paper enrollment packet. Eligibility includes the following: – Surgery must be under general anesthesia. – Patient must be 13 years or older. – Patient must have the ability to read and understand English. – Awareness of recall of events or sensations during surgery when you should have been asleep and unaware.

FOLLOW-UP CLOSED CLAIMS DATA

• Awareness claims accounted for 79 (1.9%) of 4,183 claims in the database.

• There were 18 claims for awake paralysis, most of which represented substandard care involving errors in labeling and administration. • There were 61 claims for recall during general anesthesia, most of which were likely in women with nitrous–narcotic–relaxant techniques.

REFERENCES

1. merican Society of Anesthesiologists Task Force on Intraoperative Awareness. Practice advisory for intraoperative awareness and brain function monitoring. Anesthesiology. 2006;104:847–864.

2. Sebel PS, Bowdle TA, Ghoneim MM, et al. The incidence of awareness during anesthesia: A multicenter United States study. Anesth Analg. 2004;99(3):833–839.

3. Sandin RH, Enlund G, Samuelsson P, et al. Awareness during anesthesia: A prospective case study. Lancet. 2000;355:707–711. 4. Domino KB, Posner KL, Caplan RA, et al. Awareness during anesthesia: A closed claims analysis. Anesthesiology. 1999;90:1053–1061. 5. Spitellie PH, Holmes MA, Domino KB. Awareness during anesthesia. Anesthesiology Clin N Am. 2002;20:555–570. 6. Mashour GA, Wang LY, Turner CR, et al. A retrospective study of intraoperative awareness with methodological implications. Anesth Analg. 2009;108:521–526.

ADDITIONAL READING

• Myles P, Leslie K, McNeil J, et al. A randomised controlled trial of BIS monitoring to prevent awareness during anaesthesia: The B-Aware Trial. Lancet. 2004;363:1757–1763. • Webb RK, Currie M, Morgan CA, et al. The Australian Incident Monitoring Study: An analysis of 2000 incident forms. Anaesth Intens Care. 1993;21:520–528.

CLINICAL PEARLS

• Awareness during general anesthesia is unintentional consciousness or awareness of events happening during an operation either with or without pain sensations. It is a frightening experience that can lead to debilitating emotional injury and even post-traumatic stress disorder. • ASA guidelines suggest considering premedication with amnestics, particularly when light anesthesia is anticipated, administering more than a “sleep dose” of induction agent, and avoiding muscle paralysis unless necessary. • Light anesthesia is the most common cause of awareness.

BARIATRIC SURGERY John D. Kot, MD Judith A. Turner, MD, PhD

BASICS DESCRIPTION General

• Bariatric surgery includes a variety of surgical weight loss procedures indicated in the treatment of morbid obesity (defined as an absolute BMI ≥40 kg/m2 or BMI ≥35 kg/m2 combined with obesity-related comorbidities). Surgical intervention for less obese individuals who do not meet these criteria is controversial. • Bariatric surgery may be classified as malabsorptive, restrictive, or mixed. – Malabsorptive procedures, such as biliopancreatic bypass, are rare due to problems associated with severe malabsorption. – Restrictive procedures diminish gastric volume and include gastric banding and sleeve gastrectomy. – Roux-en-Y gastric bypass (RYGB) has become the “gold standard,” and combine gastric restriction with minimal malabsorption. • Laparoscopy is the preferred and more common approach due to a significant reduction in postoperative complications and length of hospital stay as compared to an open procedure. • Medical problems associated with obesity may include hypertension, heart disease, stroke, type 2 diabetes, metabolic syndrome, obstructive sleep apnea (OSA), respiratory insufficiency, pulmonary hypertension, thromboembolism, hepatic steatosis, certain cancers, osteoarthritis, and depression. • Eligible patients usually have failed supervised medical treatment, have undergone psychological screening, and have demonstrated lifestyle changes for a specified length of time in order to optimize surgical benefit. Position

• Reverse Trendelenburg position (RTP) with back extension for laparoscopic surgery • Supine for open procedures • Adequate patient straps and padding of pressure points due to increased risk of slipping and neuropathy Incision

• 4–6 port sites for laparoscopy • Midline for open

Approximate Time 2–4 hours

EBL Expected 25–100 mL

Hospital Stay 2–3 days

Special Equipment for Surgery

• Large OR table with an optional inflatable mat in place to facilitate patient movement after surgery • Laparoscopic equipment (including adequately long instruments) or large retractors • Orogastric (OG) tube with inflatable gastric balloon

EPIDEMIOLOGY Prevalence

Laparoscopic RYGB is currently the most common bariatric procedure. Prevalence

In the US in 2008, it is estimated that >200,000 total bariatric procedures were performed (and has been increasing yearly). Morbidity

• Wound infection: 10% with open versus 1% with laparoscopic • Hernia: 8% with open versus <1% with laparoscopic

Mortality

• Overall risk is <1%. • Mortality risk factors include age >45 years, hypertension, male sex, risk factors for PE, and BMI >50 kg/m2. – 4 or more risk factors increase mortality risk to 2.4%. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patient population with significant comorbidities • Preoperative airway examination is critical, and additional airway equipment should be readily available. • High risk for DVT/PE, thus preoperative heparin SC and/or an IVC filter are essential. IVC filters are typically reserved for patients with a history of DVT, PE, or BMI near 60 kg/m2. • Except for succinylcholine, drug dosing should be based upon lean body mass (LBM). • Special attention should be made to patient positioning and padding of pressure points to mitigate nerve injury. • Avoid endogastric tubes, other than the intragastric balloon tube that may be placed at the surgeon’s request; this includes esophageal temperature probes. • Judicious use of sedatives and analgesics to minimize respiratory impairment

PREOPERATIVE ASSESSMENT

SYMPTOMS

As related to comorbidities: Chest pain, dyspnea, somnolence, GERD History

• Careful assessment of comorbidities especially cardiopulmonary • Known difficult airway • Previous bariatric surgery • History of DVT or PE

Signs/Physical Exam

• Thorough airway examination • Any evidence of cardiac failure: Pulmonary rales, additional heart sounds, increased JVD

MEDICATIONS

• Weight loss medications: Sibutramine may worsen hypertension, and orlistat may lead to deficiencies in fat-soluble vitamins (A, D, E, K). • Consider holding diuretics and ACE inhibitors given bowel prep and the potential for hypotension especially if the procedure is in the reverse Trendelenburg position. • Hold oral diabetic medications on the morning of surgery.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Check blood glucose • Electrolytes if renal insufficiency • PT/PTT, INR if taking orlistat or previous bariatric surgery given potential for chronic vitamin K deficiency • Consider liver function tests • Consider baseline ABG if respiratory impairment is significant • EKG, further cardiac testing (Echo, Stress) as indicated • Consider CXR as indicated

CONCOMITANT ORGAN DYSFUNCTION

• Neurologic: Cerebrovascular disease • Cardiac disease: Hypertension, coronary artery disease • Respiratory impairment: Restrictive disease, OSA with possible pulmonary hypertension (chronic hypoxia) • Renal insufficiency • Hepatic steatosis • Metabolic: Diabetes, hypercholesterolemia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Heparin SC to decrease risk of DVT • Antacid as indicated • Judicious use of anxiolytics

Special Concerns for Informed Consent • Potential to convert to open • Potential for postoperative intubation

Antibiotics/Common Organisms

Cefoxitin unless precluded by drug allergies INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia • Epidural for postoperative analgesia if an open procedure is planned

Monitors

• Standard ASA monitors • May need to place a NIBP cuff on the wrist or ankle given body habitus • Avoid esophageal temperature monitoring since the probe may become inadvertently entrapped • Invasive monitors only as indicated and central venous catheter if peripheral access proves difficult • Foley catheter to monitor urine output for adequate volume resuscitation

Induction/Airway Management

• Pre-oxygenation in RTP to maximize FRC. Some anaesthetists administer CPAP for several minutes prior to induction, as this may decrease atelectasis after the induction of anesthesia. • Awake fiberoptic intubation if warranted • Rapid-sequence intubation if indicated • Proper patient positioning is crucial to facilitate direct laryngoscopy. The upper thorax is “ramped” with either blankets or by elevating the back of the table 30–40° and extending the head until the external auditory meatus is level with the sternal notch. • Additional difficult airway equipment should be readily accessible. • Drug dosing should be based on LBM, rather than ideal or total body weight (IBW, TBW); LBM is calculated by adding approximately 20–50% of the difference between TBW and IBW to IBW. • Only succinylcholine is dosed based on TBW as pseudocholinesterase levels increase proportionate to body weight.

Maintenance

• Any anesthetic technique is acceptable although desflurane may improve recovery time. • Ventilation. – An FiO2 of 0.5 may decrease atelectasis (the nitrogen in air prevents absorption atelectasis; it is poorly soluble in blood and thus serves as a “filler" within alveoli, hence

keeping them open). – PEEP is often administered to decrease atelectasis; increased values may be needed but must be balanced with decreasing venous return to the heart. – Recruitment maneuvers may be necessary to address atelectasis. – Adjust ventilation accordingly to maintain normocapnia during laparoscopic CO2

insufflation. • Avoid N2O due to the possibility of bowel distention, high oxygen demands of the obese,

and worsening of any underlying pulmonary hypertension. • Muscle relaxation is required to facilitate surgery and ventilation. • The surgical team will request the placement of oral intragastric tubes to help size the gastric pouch, as well as perform leak tests with methylene blue. Lubrication, neck flexion, and the use of a laryngoscope may be appropriate. No other tubes should be in the esophagus/stomach. • Narcotics should be judiciously administered to avoid postoperative respiratory complications; remifentanil may be preferable intraoperatively. • Fluids. Address NPO and bowel prep, as well as increased maintenance fluid requirements to prevent postoperative ATN.

Extubation/Emergence

• Full reversal of neuromuscular blockade is essential. • Place the patient in RTP to maximize FRC and minimize work of breathing. • Antiemetics to mitigate PONV risk • Consider the placement of an airway exchange catheter if airway management was difficult.

FOLLOW-UP BED ACUITY

• Need for mechanical ventilation and/or ICU care is rare but more common after an open procedure. • Patients with known or suspected OSA will require a monitored bed. CPAP and BiPAP have been shown to be safe although there is theoretical concern of anastomotic injury due to the pressurized air.

ANALGESIA

• Pain is typically mild with laparoscopic procedures. • Local anesthetic infiltration at incision sites may be helpful initially. • If the procedure was open, an epidural catheter or dexmedetomidine may be preferable to limit respiratory depression. • Avoid NSAIDs given the risk for gastric ulceration.

COMPLICATIONS

• Anastomotic leak (2%) and stricture (10%) • Respiratory complications (most common) • Venous thromboembolism

• Laparoscopy related: Gas embolism, pneumothorax, pneumomediastinum • Stricture or obstruction • Wound infection (increased with open) • Incisional hernia (increased with open) • Dumping syndrome and malnutrition with bypass procedures

PROGNOSIS

• RYGB yields an average loss of 50–60% excess body weight and BMI decrease of 10 kg/m2 within the first 12–24 months. • Majority experience resolution of other comorbidities: Diabetes (90%), hypertension and hyperlipidemia (70%), and OSA. • Overall, significantly reduced long-term mortality

REFERENCES

1. Bguyen NT, Goldman C, Rosenquist CJ, et al. Laparoscopic versus open bypass: A randomized study of outcomes, quality of life, and costs. Ann Surg. 2001;234:279–291. 2. Demaria EJ, Murr M, Byrne TK, et al. Validation of the obesity surgery mortality risk score in a multicenter study proves it stratifies mortality risk in patients undergoing gastric bypass for morbid obesity. Ann Surg. 2007;246(4):578–582. 3. Huerta S, DeShields S, Shipner R, et al. Safety and efficacy of postoperative continuous positive airway pressure to prevent pulmonary complications after Roux-en-Y gastric bypass. J Gastrointest Surg. 2002;6:354–358. 4. Larson CP, Dutson E. The bariatric challenge. Curr Rev Clin Anesth. 2010;30:207–214. 5. NIH conference: Gastrointestinal surgery for severe obesity—Consensus Development Conference Panel. Ann Intern Med. 1991;115:956–961. 6. Ogunnaike BO, Jones SB, Jones DB, et al. Anesthetic considerations for bariatric surgery. Anesth Analg. 2002;95:1793–1805. See Also (Topic, Algorithm, Electronic Media Element) • Continuous positive airway pressure (CPAP) • Laparoscopy • Diabetes mellitus • Laryngoscopy positioning

CODES ICD9 • 278.01 Morbid obesity • V45.86 Bariatric surgery status ICD10 • E66.01 Morbid (severe) obesity due to excess calories

• Z98.84 Bariatric surgery status

CLINICAL PEARLS

• Patient population with significant comorbidities, including cardiovascular disease • Preoperative airway examination is critical; additional airway equipment should be readily available. • High risk for DVT/PE; preoperative heparin SC and/or IVC filter are essential. • Judicious use of sedatives and analgesics to minimize respiratory impairment • Laparoscopy is the preferred and more common approach due to a significant reduction in postoperative complications and hospital stay as compared to an open procedure. Laparoscopic RYGB is the “gold standard” bariatric procedure.

BIER BLOCK Angela T. Hsu, MD

BASICS DESCRIPTION

• Intravenous regional anesthesia (IVRA) involves the administration of local anesthetic distal to a tourniquet. It is a simple, safe, and reliable technique to provide anesthesia for extremity surgery. • The technique is also known as a Bier block, named after the German surgeon August Bier, who first described the technique in 1908. • Benefits of this technique: – Easy to perform; it requires only the ability to perform venipuncture. – Low failure rate – Fast and reliable onset within 5 minutes – Provides muscle relaxation for a surgical procedure – Rapid recovery • Limitations of this technique: – Anesthesia is limited to the area distal to the tourniquet. – The maximum duration of anesthesia is usually limited to 1 hour, secondary to the onset of tourniquet pain. – There is a concern for systemic toxicity if inadequate tourniquet inflation, early deflation, or inadvertent deflation occurs. – Lack of postoperative pain relief PHYSIOLOGY PRINCIPLES

• The mechanism whereby IVRA provides anesthesia is controversial. • Via studies using radioisotope-labeled local anesthetic, the following mechanism has been proposed: – Initially, the local anesthetic works on free nerve endings by binding to intracellular sodium channels and inhibiting the initiation and propagation of nerve impulses. – This is later followed by blockade of proximal nerve trunks, as the local anesthetic travels from superficial veins to deep venules of nerve trunks. The theory of nerve trunk site of action has been further supported because distal extremity anesthesia is achieved despite application of an additional distal tourniquet that would inhibit medication distribution to these tissues. • Ischemia and compression of nerve trunks have been proposed as a late mechanism of anesthesia and paralysis. ANATOMY

• Bier block can be performed for upper extremity surgery below the elbow, or lower extremity surgery below the knee.

– This technique is particularly suitable for surgery of distal extremities: hand, forearm, foot, and ankle.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Local anesthetic systemic toxicity can result from early tourniquet deflation, inadequate inflation, or inadvertent premature deflation. – After tourniquet release, patients may complain of dizziness, tinnitus, and perioral numbness. – Tourniquet malfunction may lead to the premature release of local anesthetic to the systemic circulation, resulting in severe local anesthetic toxicity with seizures and cardiovascular instability.

PERIOPERATIVE RELEVANCE

• IVRA is ideal for outpatient surgical procedures of the distal extremity. It provides a bloodless surgical field and anesthesia that is reliable in onset and offset. In comparison to general anesthesia, patients may be discharged earlier and have a decreased incidence of postoperative nausea and vomiting. • Patient selection: – Patients with significant anxiety are unlikely to tolerate tourniquet-related pain. Administering IV anxiolytic may help, but this may negate the benefits in discharge time and cost. – Procedure duration: Procedures longer than 60–90 minutes are not well tolerated secondary to tourniquet pain. • Contraindications: – Avoid this technique in patients who cannot tolerate extremity ischemia from the tourniquet. Raynaud’s disease Homozygous sickle cell disease (usually tolerated in heterozygous sickle cell disease) Caution in crush injuries (viable tissues will be subjected to further ischemia) • Medication selection: – Prilocaine and lidocaine are commonly used due to their high therapeutic index. – Prilocaine: Usual adult dose is 40 mL of 0.5% prilocaine. Recommended maximum dose is 6 mg/kg. Because of concerns with methemoglobinemia, prilocaine is not as popular as lidocaine in clinical practice. However, methemoglobinemia is usually not a concern until prilocaine levels reach 10 mg/kg. – Lidocaine: Usual adult dose is also 40 mL of 0.5% lidocaine. Recommended maximum dose is 5 mg/kg. – Bupivacaine is not recommended secondary to its cardiotoxic potential, and reports of several deaths. – Ensure that the local anesthetic is preservative-free and does not contain epinephrine. – Several adjuvants (e.g., clonidine, narcotics, neostigmine, muscle relaxants, ketorolac) have been studied to improve block quality, tourniquet pain, or postoperative analgesia.

• Technique: – Prepare equipment: Test the double-lumen tourniquet and ensure that resuscitative equipment is nearby. – In the extremity being operated on, place a 20–22 g IV in a vein distal to the surgical site. – Place a 2nd IV in another limb for administration of fluids or other IV medications that will be used during the procedure. – Place a double-lumen tourniquet on the upper arm or thigh; do not inflate. Avoid tourniquet placement on the forearm or lower leg since arterial compression is inadequate at these locations. – The extremity is then elevated and exsanguinated beginning distally via an Esmarch or rubber bandage. Ensure that even the digits are exsanguinated. – The proximal tourniquet is inflated to 100 mm Hg above pulse-occlusion pressure. The pulse-occlusion pressure is best determined by loss of the pulse oximeter signal on the finger or toe. – Remove the Esmarch or rubber bandage. Confirm the absence of the radial or dorsalis pedis pulse. – Inject local anesthetic slowly (in the distal IV catheter of the operative extremity). Remove the IV catheter and hold pressure at the IV site. – The patient should be ready for surgical incision within a few minutes. – When the patient complains of tourniquet pain, the distal cuff is inflated. The proximal cuff is released after distal cuff inflation. – After the surgery is completed, gradual release of the distal lumen is advised. The minimum recommended time before the tourniquet can be deflated is 20 minutes to avoid local anesthetic toxicity.

REFERENCES

1. Blackburn EW, Shafritz AB. Why do Bier blocks work for hand surgery… most of the time? J Hand Surg Am. 2010;35(6):1022–1024. 2. Brown EM, McGriff JT, Malinowski RW. Intravenous regional anaesthesia (Bier block): Review of 20 years’ experience. Can J Anaesth. 1989;36(3):307–310. 3. Rawal N. Intravenous regional anesthesia. Tech Reg Anesth Pain Manage. 2000;4(1):51–53. See Also (Topic, Algorithm, Electronic Media Element) • Local anesthetic systemic toxicity • Methemoglobinemia

CLINICAL PEARLS

• Bandage wrapping during exsanguination can cause significant pain in a fractured extremity. An alternative is to elevate the extremity for 30 seconds while applying firm pressure to occlude the brachial or femoral artery. The tourniquet is then inflated after this method of extremity exsanguination. • Typically for upper extremity block, 40 mL of 0.5% lidocaine or prilocaine is used. For larger or muscular patients, the dose can be increased to 50 mL. For small or frail patients,

the volume can be decreased to 30 mL. • For the lower extremity, usually a larger volume is utilized to assure adequate distribution of drug. One technique is 150 mL of 0.25% lidocaine. • Make sure the local anesthetic contains no epinephrine. It is also recommended to have preservative-free local anesthetic, although a review of 1,906 cases using local anesthetic with preservative did not reveal ill-effects. • Inform the patient that with this regional technique, the extremity may feel warm, numb, or tingly. The skin will also appear mottled. This is normal. • Maximum continuous tourniquet inflation time should be limited to 90 minutes secondary to concern of extremity ischemia. • Procedures longer than 90 minutes using Bier block as anesthesia are possible with a short period of tourniquet release. In these cases, the IV cannula is kept in place during surgery. After 1 hour, the tourniquet is deflated for 5 minutes. The surgeon elevates the arm and applies a sterile Esmarch bandage, reinflates the tourniquet, and administers 50% of initial local anesthetic dose. This may be repeated if necessary.

BLALOCK-TAUSSIG (BT) SHUNT Alison R. Perate, MD

BASICS DESCRIPTION General

• Surgeon Alfred Blalock and cardiologist Helen Taussig developed the procedure after noting that cyanotic children with a patent ductus arteriosus (PDA) did better than those without a PDA. The first Blalock–Taussig (BT) shunt was performed in 1944 on a human with Tetralogy of Fallot (TOF). • The BT shunt is a palliative surgery for cyanotic heart defects with limited pulmonary blood flow/ductal dependant lesions. – Single ventricle physiology (most common indication) – Tetralogy of Fallot – Tricuspid atresia – Ebstein anomaly – Small pulmonary arteries – Pulmonary stenosis • The shunt connects the right subclavian artery to the right pulmonary artery (PA); the left PA can be used as well. This increases the amount of deoxygenated blood directed to the lungs. – Classic BT shunt: The subclavian or carotid artery is anastomosed directly to the PA. – Modified BT shunt uses artificial material (GORTEX) 4–5 mm in diameter to make the aorticopulmonary connection. Position

Supine, fully prepped from neck to groin for cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) access if needed Incision

• Historically, the procedure was performed via a lateral thoracotomy at the level of the 4th intercostal space. However, this approach had limited access to small neonatal anatomy, commits the surgeon to the side of entry, makes it difficult to ligate the PDA if done via a right thoracotomy, and has a risk of flail scapula from an incision through the latissimus dorsi muscle. • Most institutions now use a median sternotomy; this approach allows for improved access, easier conversion to CPB, augmentation for diminutive PAs, and less distortion of vascular anatomy. Approximate Time

Dependent on the surgeon’s experience; approximately 2–3 hours

EBL Expected

• Surgeon dependant • Typically minimal (∼50 mL) when only a BT shunt is being performed • May need to transfuse blood to maintain euvolemia

Hospital Stay

• Highly dependant on the underlying congenital heart disease that necessitated the shunt • If the shunt remains patent and there are no complications, discharge to home is usually between 8 and 15 days. • Most surgeons require the patient to stay reasonably close to the hospital for the first few weeks due to the risk of shunt occlusion.

Special Equipment for Surgery

• CPB machine should be in the room, prepped, and ready to use. • ECMO back-up/capability

EPIDEMIOLOGY Incidence

• Unknown number worldwide • All congenital heart disease (CHD) = 8/1,000 • Cyanotic CHD is estimated at 25% of all CHD; corresponds to 2/1,000. • Most registry data (Canada and Europe) quote an annual incidence of 1.5/1,000 live births.

Prevalence

Overall prevalence is increasing as therapies improve. Morbidity

• Morbidity is largely related to the experience of both the surgeon and anesthesiologist as well as the postoperative care (ICU). • Risk of neurologic sequelae from surgery

Mortality

• Dependant on the complexity of the underlying heart defect/comorbidities • Highest mortality of the 3 stages of the Fontan procedures • Increased when performed in neonates compared to older children

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients have “duct-dependent” lesions; therefore, pulmonary blood flow can be tenuous. Prevent any condition that would increase pulmonary vascular resistance (PVR), such as hypothermia, acidosis, hypercapnia, or hypoxia. • The maintenance of adequate pressures is necessary to prevent shunt occlusion. This is accomplished via adequate blood volume as well as vasopressors if necessary.

PREOPERATIVE ASSESSMENT

SYMPTOMS

Because CHD presents in the neonatal period, feeding intolerance is a common symptom reflecting decreased exercise tolerance. History

• With improvements in fetal ultrasound technology, many lesions are now detected in utero. • Those who are postnatally diagnosed are often cyanotic at birth, or when the PDA closes.

Signs/Physical Exam

• Murmur—with a diastolic component • PaO2 <150 mm Hg on 100% FiO2

• Tachypnea, diaphoresis, central cyanosis • Hepatomegaly

MEDICATIONS

Patients arrive on prostaglandins to maintain PDA patency. Most cyanotic heart disease is due to inadequate blood flow to the lungs; If the ductus closes, pulmonary blood flow will be inadequate and cardiopulmonary collapse will occur. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Chest radiograph: Look for signs of heart failure and lung congestion/fluid accumulation • Echocardiogram: To determine the exact cardiac anatomy and nature of the lesion causing the cyanosis • CBC, chemistry, coagulation panel • Cardiac MRI now gaining popularity

CONCOMITANT ORGAN DYSFUNCTION • Heart failure • Acidosis from malperfusion/hypoxemia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics are not usually necessary due to the young age of the patient. If the patient is older, midazolam or pentobarbital may be considered. • Maintain the prostaglandin infusion

Special Concerns for Informed Consent

Parents should be made aware of the risk of complications/death. Antibiotics/Common Organisms

• Important in the modified BT shunt due to placement of the indwelling gortex graft • Skin flora

INTRAOPERATIVE CARE Choice of Anesthesia

General endotracheal anesthesia Monitors

• Standard ASA monitors • Arterial line on the contralateral side of the shunt can be placed postinduction. • 2 well-functioning IVs; if performed in the immediate postnatal period, an umbilical vein line allows for the measurement of venous pressures. • Surgeon may place right atrial lines prior to chest closure for right-sided pressures. • Urine Foley catheter

Induction/Airway Management

• Bag mask ventilation and intubation should avoid hypercapnia, hypoxia, or coughing and bucking as these derangement increase the pulmonary vascular resistance. • Aggressive hydration is not usually needed as TOF repair is most commonly done as a single-stage operation and does not undergo BT shunts anymore. In the TOF subset, there is concern for RVOT obstruction in the face of inadequate intravascular volume. Adequate, but not overaggressive, hydration is required to prevent this.

Maintenance

• Gas (isoflurane usually) with fentanyl or other short-acting opioids • Standard paralysis doses of pancuronium or vecuronium as most of these patients are extubated at the conclusion of surgery. • Hypotension is often caused by surgical manipulation of great vessels. • Neuromonitoring is not currently used, but is an evolving area of research. • On clamping of the PA, some patients (in particular neonates) may develop profound desaturation due to increases in dead space. This can also cause increases in the PaCO2,

causing the PVR to rise even further and reversing flow through the PDA (ceases pulmonary blood flow). This will require going on CPB for the completion of surgery. • Good surgical technique will minimize the effect of traction on the lung. • In classical BT shunt, arterial flow to the ipsilateral arm is often compromised and can result in ischemia. Modified BT shunt decreases this risk by maintaining flow to the arm. • Ionotropes (such as epinephrine) are often utilized when weaning from CPB, until the blood pressure is stabilized. • Heparin is utilized to prevent clot formation during clamping of arteries; this can increase the patient’s risk of bleeding. • If the shunt is too large, overcirculation of the pulmonary vasculature can occur, resulting in pulmonary edema and desaturation.

Extubation/Emergence

• Depending on the underlying heart defect, most can be extubated immediately after surgery.

• Patient must be strong, awake, and able to protect their airway in order to be extubated. Hemodynamics should also be stable, with minimal ionotropic support. ABG results should not reveal acidosis, which could reflect underperfusion of tissues.

FOLLOW-UP BED ACUITY Cardiac ICU

ANALGESIA

• IV opioids: morphine is often administered (easy to titrate); however other opioids are acceptable and based upon practitioner and institution preferences. If the patient is older (mental capacity >7 years of age), PCA may be considered. • No current studies in the pediatric population for regional techniques

COMPLICATIONS

• Shunt occlusion—surgical emergency • Pseudoaneurysm—can compress mediastinal structures • Excessive pulmonary blood flow leading to pleural effusions • Decreased diastolic pressures • Congestive heart failure • Distortion of vascular anatomy • Pulmonary artery hypoplasia • Phrenic/vagus/recurrent laryngeal nerve injury • Arrhythmias

PROGNOSIS

• Dependant on the complexity of the underlying heart defect • It is considered a palliative procedure, not curative; if done for single ventricle pathology, this is the first of 3 steps to a Fontan completion.

REFERENCES

1. Kandakure PR, Dharmapuram AK, Ramadoss N, et al. Sternotomy approach for the modified Blalock-Taussig Shunt: Is it a safe option? Asian Cardiovasc Thorac Ann. 2010;18(4):368–372. 2. Mavroudis C, Backer C. Pediatric cardiac surgery. Philadelphia: Mosby, 2003.Van Arsdell GS, Maharaj GS, Tom J, et al. What is the optimal age for repair of tetralogy of Fallot? Circulation. 2000;102(19 Suppl 3):III123–III129.Alkhulaifi AM, Lacour-Gayet F, Serraf A, et al. Systemic pulmonary shunts in neonates: Early clinical outcome and choice of surgical approach. Ann Thorac Surg. 2000;69(5):1499–1504. 3. Pearl JM, Nelson DP, Schwartz SM, et al. First-stage palliation for hypoplastic left heart syndrome in the twenty-first century. Ann Thorac Surg. 2002;73(1):331–339; discussion 339–340.

See Also (Topic, Algorithm, Electronic Media Element) • Fetal cardiovascular physiology • Cardiopulmonary bypass • Extracorporeal membrane oxygenator

CODES ICD9

746.89 Other specified congenital anomalies of heart. ICD10

Q24.8 Other specified congenital malformations of heart

CLINICAL PEARLS

• It is critical to maintain patency of the shunt in the postoperative period. Maintain adequate blood pressure and volume. Shunt occlusion is a life-threatening surgical emergency. • Patients may become severely hypoxic upon clamping of the PA. CPB must be on standby and ready to cannulate. • An A-line should be placed on the opposite side of the shunt. Otherwise when the artery is clamped, the arterial line will be useless.

BLOOD COAGULATION PHYSIOLOGY IN PREGNANCY Andrew Geller, MD Mark Zakowski, MD Sivam Ramanathan, MD

BASICS DESCRIPTION

• Normal pregnancy becomes a hypercoagulable state at 6–8 weeks of gestation and returns to the pre-pregnancy state in the 1st month after delivery (1). • Hypercoagulability during pregnancy minimizes blood loss during delivery and in the postpartum period (2).

PHYSIOLOGY PRINCIPLES

• Hypercoagulability during pregnancy is achieved via several mechanisms: – Increased levels of procoagulants: Factors V, VII, VIII, IX, X, and XII; vWF; fibrinogen; prothrombin. – Decreased levels of anticoagulants: Factors XI and XIII; protein S. – Decreased fibrinolysis is caused by increased concentrations of plasminogen activator inhibitors 1 and 2 (1,3).

DISEASE/PATHOPHYSIOLOGY

• Thromboembolism: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are the greatest cause of morbidity and mortality in the parturient, occurring in 1 in 1,600 pregnancies. – Contributing factors include: Hypercoagulable state, increased venous distention and obstruction due to compression of the inferior vena cava by the gravid uterus. – Thrombus primarily occurs in the venous system of the legs or, less commonly, in the pelvic veins. – Diagnostic tests include ultrasound imaging of the deep venous system of the lower extremities and D-dimer levels. If PE is suspected, V/Q scan, MRI/MRA, or CT angiogram is indicated. – Prophylaxis is recommended for women at high risk for thromboembolism (e.g., bed rest, postsurgical procedure, or pre-existing hypercoagulable disease state). Thromboprophylaxis is accomplished with heparin SQ q12h (adjusted to the mid-range of therapeutic PTT), dalteparin 200 U/kg SQ q24h, or enoxaparin 1 mg/kg q12h. Thromboprophylaxis is discontinued at the time of delivery. • Gestational thrombocytopenia: Platelet counts 70,000–150,000/μL. – Occurs in ∼10% of pregnancies, usually in the third trimester. – Proposed etiology includes increased plasma volume (dilutional) and increased platelet clearance. – Condition usually does not require treatment.

• Idiopathic thrombocytopenia purpura (ITP) – Occurs in ∼3% of pregnancies, usually manifests in the first or second trimester. – Treatment is with corticosteroids and/or intravenous IgG. • Hemolysis, Elevated Liver enzymes, Low Platelet counts (HELLP) Syndrome – Form of severe preeclampsia that can start after 20 weeks of gestation and up to 2 days post-delivery. – Thrombocytopenia results from increased anti-platelet IgG levels, activation of the coagulation cascade (platelet consumption), and platelet sequestration in the spleen (4,5). – Mortality results from liver rupture, disseminated intravascular coagulation (DIC), acute renal failure, acute respiratory distress syndrome (ARDS), shock, and stroke. – Management is supportive care. Seizure prophylaxis with intravenous magnesium sulfate. Blood pressure control for systolic pressure >160 mm Hg or diastolic pressure >90 mm Hg. – Definitive treatment is delivery of the fetus and placenta. • Thrombotic thrombocytopenia purpura (TTP) – Thrombocytopenia is a result of platelet aggregation due to impaired vWF protease. – Occurs anytime during pregnancy (first trimester through postpartum period). – Severe cases can be treated with plasmapheresis. • Hemolytic uremic syndrome (HUS) – Microangiopathic hemolytic anemia from microvascular injury (6). – 90% of cases occur postpartum with a mean onset of 26 days postdelivery (7). – May require plasmapheresis

PERIOPERATIVE RELEVANCE

• Hypercoagulable states increase the risk of thromboembolism. – Complications include uteroplacental thrombosis, fetal loss, DVT, PE, CVA, and cortical venous thrombosis. – Prophylaxis against thromboembolism (following surgical procedures and Cesarean section) include: Graduated compression stockings, sequential leg compression devices, early ambulation, and thromboprophylaxis. • Some inherited congenital coagulopathies may improve or worsen depending on whether the given factor increases or decreases with pregnancy. – Hypofibrinogenemia and von Willebrand disease may improve. – Factor XI deficiency may worsen. • Hypocoagulable states may cause: – Increased risk of postpartum hemorrhage – Increased risk of placental abruption – Increased risk of non-reassuring fetal status during labor – A contraindication to neuraxial anesthesia due to increased risk of bleeding and epidural hematoma formation. Generally a stable platelet count >80,000/mL is sufficient for neuraxial anesthesia.

ALERT • Management of anticoagulation pre-delivery

– Low molecular weight heparin (LMWH) should be switched to SQ or IV unfractionated heparin 36 hours before elective induction or C-section. – Many prefer to switch to unfractionated heparin at 36 weeks, to avoid going into labor on LMWH, which might delay or preclude epidural placement. – IV heparin should be turned off 4–6 hours before anticipated delivery. • Management of anticoagulation prior to neuraxial block – SQ heparin is not a contraindication for neuroaxial anesthesia if the total daily dose is <10,000 U divided q12h. – Conventional doses of fractionated LMWH require waiting at least 12 hours after the last dose to perform a regional block; if higher doses are used, wait 24 hours. – IV heparin can be administered 1 hour after a neuraxial block is in place. – Removal of epidural catheters should occur at least 2–4 hours after the last heparin dose (PTT measurement may be warranted). – Restart fractionated or unfractionated (regular) heparin (for DVT prophylaxis) at least 2 hours after removal of the epidural catheter. Doses of heparin (5,000 U SQ q12h) and LMWH (e.g., enoxaparin 1 mg/kg SQ q24h) should not increase the risk of hematoma formation with neuraxial blockade after delivery if guidelines are strictly observed. • Postoperative anticoagulation guidelines: – Prophylaxis: Wait 12 hours after vaginal delivery to restart heparin and 24 hours after Cesarean delivery for LMWH. – Therapeutic: Wait 24 hours after delivery (8).

REFERENCES

1. Brenner B. Haemostatic changes in pregnancy. Thromb Res. 2004;114:409–414. 2. Crowley JP. Coagulopathy and bleeding in the parturient patient: Recent information has helped in the identification of individuals at special risk. R I Med J. 1989;72:135–143. 3. Cerneca F, Ricci G, Simeone R, et al. Coagulation and fibrinolysis changes in normal pregnancy: Increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol. 1997;73:31–36. 4. Leduc L, Wheeler JM, Kirshon B, et al. Coagulation profile in severe preeclampsia. Obstet Gynecol. 1992;79:14–18. 5. Burrows RF, Hunter DJ, Andrew M, et al. A prospective study investigating the mechanism of thrombocytopenia in preeclampsia. Obstet Gynecol. 1987;70:334–338. 6. McCrae KR, Cines DB. Thrombotic microangiopathy during pregnancy. Semin Hematol. 1997;34:148–158. 7. Esplin MS, Branch DW. Diagnosis and management of thrombotic microangiopathies during pregnancy. Clin Obstet Gynecol. 1999;42:360–367. 8. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy. American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med. 2010;35:64– 101.

ADDITIONAL READING

• Chestnut D, Polley L, Tsen L, et al. Chestnut’s obstetric anesthesia, 4th ed., 2009, chap. 43. • Hoffman R, Benz EJ, Shattil SJ, et al. Hematology: Basic principles and practice, 5th ed. Churchill Livingstone, chap. 161.

See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary embolism • Preeclampsia • Thrombocytopenia

CLINICAL PEARLS

• Patients with a history of an early pregnancy loss need to be worked up for genetic disorders of coagulation. • Hypercoagulable states are a leading cause of maternal mortality in the world because of the risk of PE. • Symptoms of DVT, PE, and cortical vein thrombosis need to be evaluated and have a low threshold for workup. • DIC in pregnancy is associated with dead fetus syndrome, preeclampsia, HELLP syndrome, placental abruption, massive transfusion, uterine rupture, and amniotic fluid embolism. • Pregnant women on anticoagulants need coordination and correct timing of medication, regional anesthesia, and delivery per guidelines.

BLOOD FLOW RESISTANCE Teodora Orhideea Nicolescu, MD

BASICS DESCRIPTION

• Blood flow resistance (BFR) is the impedance offered by the blood vessels and its interactions with the flowing blood. Conductance is the reciprocal of BFR. • The basics of BFR are adapted from Ohm’s impedance law in electricity: R = V/I where R is resistance, V is voltage, and I is current. Extrapolation of these factors and concepts to the vascular system is as follows: – Resistance (R): Equivalent to the vascular resistance and measured in dynes × seconds/cm5 (or Woods units) – Voltage (V): Equivalent to the pressure difference across the area being discussed and referred to as the ΔP – Current (I): Equivalent to the cardiac output and measured as liters/minute – R = ΔP/CO • Resistance to flow can also include additional elements; for example, when expressed across a valve it will be related to the valve size as well. PHYSIOLOGY PRINCIPLES

• BFR is expressed as the ratio between the pressure gradient (arterial and venous pressure difference) and the flow of blood. Factors affecting vascular resistance are arteriole radius, viscosity, and length. • Arteriole radius: Resistance is inversely proportional to the fourth power of the radius (r4). Radius is affected by: – Autonomic control – Hormones: Angiotensin II, norepinephrine, and epinephrine – Metabolites: Adenosine Serotonin Endothelium-derived relaxing factor (EDRF) Prostacyclin Nitric oxide (NO) – Autoregulation is present in critical organs including the cerebral, myocardial, hepatic, and renal circulations to maintain a constant (and adequate) blood flow and delivery of oxygen and glucose across a range of mean arterial pressures. Increased flow elicits vasoconstriction and decreases blood flow, whereas decreased flow results in vasodilation to increase blood flow. • Viscosity describes the tendency of a fluid to resist flow. It is affected by the hematocrit, temperature, and flow state. • Length: Does not appreciably change in vivo; this is more applicable to airflow.

• Blood flow patterns and resistance: – Laminar flow describes low-resistance, straight-line flow. Under ideal laminar flow conditions, resistance is mostly dependent on the radius. Poiseuille’s law can be applied to measure the resistance: R = (8 × L × n)/r4, where L is length, n is viscosity, and r is radius. – Turbulent flow describes high-resistance, high-velocity flow that creates eddy currents (whirls of blood); overall flow is decreased at any given perfusion pressure compared to laminar flow.

ANATOMY

• Vessel diameter has a direct effect on the resistance of the vessel. • Arteries have 3 layers: – Intima is a smooth layer that essentially helps lower BFR (low friction). – Media has 2 components: An elastic component that is predominant in the large arteries and is responsible for the stretch-recoil vessel properties, and a muscular component predominantly present in medium-size arteries and arterioles which is responsible for changing the vessel size. – Adventitia bestows a protective and tissue-securing role; it thereby plays no role in BFR.

DISEASE/PATHOPHYSIOLOGY

• Chronic hypertension: In primary hypertension, the cardiac output increases initially, while the systemic vascular resistance (SVR) remains normal. Eventually, the cardiac output returns to normal and the SVR remains elevated. • Pulmonary hypertension: Results from an imbalance in vasoactive peptides (prostacyclin, endothelin 1, NO), which initiates smooth muscle proliferation followed by vasoconstriction and right heart pressure overload. • Temperature: Hypothermia increases blood viscosity and decreases vessel radius via vasoconstriction (in order to preserve warmth). • Hematocrit: Hemoconcentration and polycythemia vera increase blood viscosity. Anemic patients, conversely, have a decrease in blood viscosity with a consequent decrease in resistance; transfusion can, in addition to increasing oxygen-carrying capacity, increase resistance and improve blood pressure in hypotensive patients. • Prosthetic valves: As the cross-sectional area of the valve decreases from stenosis or prosthetic valve housing, BFR increases, velocity increases, and pressure decreases across the valve. This translates into a need for a large systolic pressure to drive blood forward. A1V1 = A2V2, where A = cross-sectional area and V = velocity across the valve. • Sepsis and anaphylaxis: Vasodilation decreases the BFR.

PERIOPERATIVE RELEVANCE

• BFR is often considered and discussed in regard to: – SVR: Represents the change in pressure after being ejected from the left ventricle to the pressure upon returning to the right atrium. SVR = (MAP – CVP)/CO, where MAP is mean arterial pressure, CVP is central venous pressure, and CO is cardiac output. Normal values range from 1,200 to 1,500 dynes × seconds/cm5.

– Pulmonary vascular resistance (PVR): Represents the change in pressure from the beginning (pulmonary arteries) to the end (left atrium) of the pulmonary circulation. PVR = (PAP – LAP)/CO, where PAP is the mean pulmonary artery pressure, LAP is left atrial pressure, and CO is cardiac output. Normal values range from 100 to 300 dynes × seconds/cm5. – Across heart valves: Stenotic valves and prosthetic heart valves can impose increased resistance to flow. Transvalvular gradients can be measured via cardiac catheterization or estimated/calculated with echocardiogram. • Vasopressors and inotropes – Phenylephrine: A synthetic, selective, and pure alpha-1 agonist. Receptor binding increases the release of calcium from the sarcoplasmic reticulum and causes contraction of vascular smooth muscle. This results in increased preload from venoconstriction and afterload from vasoconstriction. – Norepinephrine: Endogenously, it is released by the postsynaptic terminal of the sympathetic nervous system. When exogenously administered, it has strong alpha-1 receptor agonism at veins and arteries, resulting in increased preload and afterload. Coronary blood flow increases due to the increase in diastolic blood pressure. Side effects include an increase in PVR, mesenteric ischemia, renal failure, decreased hepatic blood flow, and peripheral hypoperfusion (digit necrosis). – Dopamine: When exogenously administered, it causes alpha-1 agonism at higher dosages (>10 mcg/kg/min). Initially, the vasoconstricting effects predominate in the skeletal muscle vascular beds; with increasing doses, circulation in the limbs may become compromised. – Epinephrine: When exogenously administered, it causes alpha-1 agonism at higher dosages. – Vasopressin: V1 receptor agonism functions to increase sarcoplasmic release of calcium

and vascular smooth muscle constriction, primarily in capillaries and small arterioles. This functions to shift blood flow away from splanchnic, muscle, fat and skin tissues to vital organs. – Phosphodiesterase inhibitors block enzymatic breakdown of cAMP to cGMP. In the myocardium, this results in increased intracellular calcium with resultant enhanced inotropy. However, in vascular smooth muscle, increased cAMP results in vasodilation. • Vasodilators – Nitrovasodilators: Nitroglycerin breaks down into NO, which consequently causes calcium sequestration within vascular smooth muscle. At lower doses, venous and coronary arteries are primarily affected; at higher doses, arterial dilation occurs. Nitroprusside similarly breaks down into NO, but has a greater effect on arterial smooth muscle. – Angiotensin-converting enzyme inhibitors (ACE I) block the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent endogenous vasoconstrictor. – Angiotensin II receptor blockers (ARBs) competitively antagonize angiotensin II binding to receptors on blood vessels. – Calcium channel blockers (CCB) block voltage-gated calcium channels in the sarcoplasmic reticulum, resulting in decreased intracellular calcium and decreased vasomotor tone. – Hydralazine is a direct vasodilator. It increases cGMP levels with resultant decreases in

calcium release from the endoplasmic reticulum causing arterial vessel dilation (diastolic pressure is decreased to a greater extent than systolic blood pressure) and venodilation. • Anesthetic medications with vasodilatory properties: – Propofol – Volatile agents – Lidocaine • Resistance to blood flow also provides the basis for calculations obtained from pulmonary artery catheter data.

EQUATIONS

• Ohm’s law: R = V/I, where R is resistance, V is voltage, and I is current • Fluid dynamics extrapolation: R = ΔP/CO, where R is resistance, ΔP is change in pressure, and CO is cardiac output • Poiseuille’s law: R = (8 × L × n)/r4, where R is resistance, L is length, n is viscosity, and r is radius

REFERENCES

1. Khalafbeigui F, Suga H, Sagawa K. Left ventricular systolic pressure-volume area correlates with oxygen consumption. Am J Physiol. 1979;237:H566–H569. 2. Maughan WL, Sunagawa K, Burkhoff D, et al. Effect of arterial impedance changes on the end-systolic pressure-volume relation. Circ Res. 1984;54:595–602. [A] 3. Rose WC, Shoukas AA. Two-port analysis of systematic of systemic venous and arterial impedances. Am J Physiol. 1993;265:H1577–H1587. [C] 4. Sasse SA, Chen PA, Mahutte CK. Relationship of changes in cardiac output to changes in heart rate in medical ICU patients. Intens Care Med. 1996;22:409–414. 5. Suga H. Total mechanical energy of a ventricle model and cardiac oxygen consumption. Am J Physiol. 1979;236:H498–H505. 6. Sunagawa K, Sagawa K. Models of ventricular contraction based on time-varying elastance. Crit Rev Biomed Eng. 1982;6:193–228. 7. Wallace A, Lam HW, Mangano DT. Linearity, load dependence, hysteresis, and clinical association of systolic and diastolic indices of left ventricular function in man. Multicenter Study of Perioperative Ischemia (McSPI) Research Group. J Card Surg. 1995;10:460–467. [B] See Also (Topic, Algorithm, Electronic Media Element) • Laminar flow • Cardiac output • Cerebral blood flow • Septic shock • Anaphylactic shock

CLINICAL PEARLS

• Circulation is influenced by the resistance of the vascular bed against which the heart is pumping. Cardiac output is directly influenced by BFR. • The most important determinant of BFR is vessel radius, which is regulated by the sympathetic nervous system (SNS), hormones, metabolites, and autoregulation. The SNS can increase the blood pressure 3-fold via increasing the heart rate, inotropy, and both arterial and venous resistances. • Therapy for arterial blood pressure management is aimed at changing the BFR (changing the vessel radius or blood flow viscosity). • Pulmonary artery catheter data and its calculations, as well as echocardiography imaging, aid with clinical decision-making and guidance of therapy. • Several anesthetic medications cause vasodilation, with resultant decreases in BFR.

BLOOD OXYGEN CARRYING CAPACITY Onyi Onuoha, MD, MPH Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• The blood oxygen-carrying capacity is the milliliters of oxygen present in 1 deciliter of blood. • In blood, oxygen can exist in 2 forms: Dissolved and attached to hemoglobin. Hemoglobin is the primary transporter of oxygen in mammals. • In the event of decreased oxygen delivery, the blood provides a limited cushion against hypoxia. PHYSIOLOGY PRINCIPLES

• Oxygen is necessary for aerobic metabolism and cell integrity. However, despite its absolute necessity, the body only has minimal storage capacity (unlike glucose). When apneic, oxygen stores are limited to the oxygen in the lungs (FRC) and the blood; both of which are unable to sustain life beyond a few minutes. • In a healthy adult at rest, oxygen consumption is ∼200–250 mL O2/min and oxygen delivery is ∼950–1,150 mL O2/min. Thus, ∼25% of the arterial oxygen is used every

minute, and the deoxygenated blood returning to the lungs has ∼75% saturation (mixed venous oxygen saturation) (1). • Hemoglobin provides the most efficient means of carrying and transporting blood. At full oxygen saturation, 1 g of hemoglobin in 1 dL of blood is capable of carrying 1.34 mL of O2. Thus, Hgb × 1.34 × SaO2 determines the milliliters of oxygen bound to hemoglobin in 1

dL of blood. Oxygen bound to hemoglobin does not exert partial pressure. • Oxygen is poorly soluble in blood with a coefficient of 0.003 milliliters of oxygen per deciliter of plasma per millimeter of mercury oxygen. Hence, a patient breathing room air with an approximate PaO2 of 100 mm Hg has 0.3 mL of oxygen dissolved in 1 dL of blood. • Oxygen–hemoglobin (O2–Hgb) dissociation curve: PaO2 on the x-axis, and SaO2 on the y-

axis. As PaO2 increases, SaO2 increases. The curve is not linear, but sigmoid in shape. This

represents hemoglobin’s desire to be fully bound or fully dissociated from oxygen; it is unstable in intermediate states. This characteristic facilitates its physiologic function; at the lungs, hemoglobin will fully saturate and at the tissue level, it will easily dissociate and unload to oxygenate the tissues. • Assuming normal hemoglobin moieties and conditions, the PaO2 is in equilibrium with oxyhemoglobin and dissolved oxygen. For example, a PaO2 of 100 mm Hg has an SpO2 of

98% and 0.3 mL O2/dL of blood. A PaO2 of 500 mm Hg has an SpO2 of 100% and 1.5 mL

O2/dL of blood. ANATOMY

• Hemoglobin is an iron-containing protein that is composed of 4 polypeptide chains or subunits. The iron-containing heme group of each polypeptide reversibly binds up to 4 molecules of oxygen (2). • The adult hemoglobin (HbA) molecule is made of 2α globin and 2β globin subunits. • The binding of the first oxygen molecule to hemoglobin induces conformational changes in the structure of the hemoglobin that allows the binding of other molecules of oxygen more readily. At normal resting conditions, 25% of the oxygen bound to hemoglobin is extracted by the tissues (equivalent to a partial pressure of 40 mm Hg). • Fetal hemoglobin (HbF), on the other hand, has 2α and 2γ subunits that possess a strong affinity for oxygen. The fetus is exposed to much lower oxygen pressures from the placenta; ∼21% of the level found in the adult lung (1). DISEASE/PATHOPHYSIOLOGY

• Low oxygen-carrying capacity is the result of a low PaO2, low hemoglobin, impaired

oxygen-to-hemoglobin binding, or an increased oxygen demand/consumption. – Low PaO2: Hypoxic mixture (low inspired oxygen), hypoventilation, V/Q mismatching,

shunting, impaired diffusion – Low hemoglobin: Chronic or acute anemia – Impaired oxygen-to-hemoglobin binding: Abnormal hemoglobins (fetal, thalassemia, sickle cell disease), carboxyhemoglobin, cyanhemoglobin, methemoglobin, sulfhemoglobin – Increased oxygen demand/consumption: Hyperthermia, hyperthyroidism, sepsis, pregnancy, vigorous exercise • Acute anemia: The initial hemodynamic response is a fall in systemic vascular resistance (SVR) that is partly due to the decrease in blood viscosity and in part, the result of nitric oxide-mediated vasodilation. The decrease in SVR reduces blood pressure and causes a baroreceptor-mediated neurohormonal activation, identical to that seen in patients with severe low-output heart failure. Eventually, sympathetic and renin–angiotensin–aldosterone activity cause peripheral vasoconstriction and decrease in renal blood flow and glomerular filtration rate. Kidneys retain salt and water (3). • Chronic anemia results in hemodynamic and non-hemodynamic (erythropoiesis) compensatory responses to enhance oxygen-carrying capacity (2,4). – Hemodynamic responses are complex and involve a vasodilation-mediated high-output state with neurohormonal activation (as described above in acute anemia). The highoutput state initially helps to increase oxygen transport. However, compensatory mechanisms have deleterious long-term consequences and could contribute to anemia’s role as an independent risk factor for adverse outcomes. – Non hemodynamic responses: Increased levels of 2,3-diphosphoglycerate (2,3-DPG) shift the O2–Hgb dissociation curve to the right. This is the least energy-consuming mechanism to support increased oxygen delivery to the tissues (lacks significant increase in cardiac output). Erythropoiesis also serves to increase red blood cell production. • In elevated altitudes, ventilation and heart rate are elevated with a minimum reduction in

stroke volume. In addition, plasma volume is reduced over 24–48 hours to improve the oxygen-carrying capacity of the blood. Prolonged sojourn at altitudes is compensated for with enhanced erythropoiesis and a larger hemoglobin mass, allowing for a partial or full restoration of the blood volume and arterial oxygen content.

PERIOPERATIVE RELEVANCE

• General anesthesia causes a 15% reduction in metabolic rate and a subsequent decrease in oxygen requirement. Artificial ventilation further decreases the oxygen requirement by 6% with the removal of the work of breathing. Anesthetic agents, however, do not affect the transport of oxygen by hemoglobin or its solubility in blood. • The increased utilization of oxygen when metabolic rate is increased (postoperative shivering, malignant hyperthermia, etc.) leads to a decrease in PaO2 which activates normal

protective responses to hypoxia (aortic and carotid chemoreceptors, sympathetic nervous system) to increase cardiac output. However, these protective responses are usually reduced by anesthetic drugs intraoperatively, and can extend into the postoperative period. • Blood transfusion: It remains the clinician’s responsibility to determine the transfusion “trigger” for an individual patient based on multiple elements that determine the demand for the delivery of oxygen and the physiological reserve. The decision should be based on the premise that the oxygen-carrying capacity is increased to prevent oxygen consumption from exceeding oxygen delivery. Additionally, the following should be considered: – Theoretically, the oxygen-carrying benefit of red blood cells should hasten recovery from respiratory failure, and transfusion would therefore be expected to shorten the duration of mechanical ventilation. However, evidence to the contrary has been reported. – Storage of packed red blood cells (pRBCs) is associated with a decline in 2,3-DPG that leads to a subsequent left shift of the O2–Hgb dissociation curve. Therefore, while

transfusion increases the patient’s hemoglobin, it results in a less efficient oxygen delivery when compared to the native hemoglobin at that same hematocrit. 2,3-DPG levels return to normal over 12–24 hours. – The need to restore blood viscosity may precede the need to restore oxygen-carrying capacity during hemodilution or anemic conditions. A minimum level of blood viscosity appears to be necessary for generating shear stress and stimulating the release of vasoregulatory factors such as nitric oxide and prostacyclin (3). – Studies in subpopulations (renal failure, Jehovah’s Witnesses, military casualties) have shown that considerably greater amounts of anemia than was previously believed can be well tolerated. – Patients that are unable to increase their cardiac output (coronary artery disease, prior/acute myocardial infarction, beta-adrenergic blockade, decreased SVR such as sepsis or post-cardiopulmonary bypass) or have impaired oxygenation (pulmonary disease, high altitude) have limited compensatory responses to hypoxia. • Isovolemic hemodilution to hemoglobin levels of 5 g/dL in normal volunteers is well tolerated. A robust cardiovascular response manifested by increases in heart rate and stroke volume leads to compensation. • Blood substitutes are being investigated to increase oxygen-carrying capacity. At this time, there are no available products for clinical use.

EQUATIONS

• Oxygen content = [(Hgb × 1.39 × SaO2) + (PaO2 × 0.003)]. Units are as follows: Hgb is in g/dL; 1.39 is mLO2/dL; SaO2 is % (0.01) but no units (5).

• Oxygen arterial content (CaO2) = [(Hgb × 1.39 × SaO2) + (PaO2 × 0.003)] (5).

• Oxygen venous content (CvO2) = [(Hgb × 1.39 × SvO2) + (PvO2 × 0.003)]. If obtained at the pulmonary artery (PAC), it is a representation of the true mixed venous oxygen (5). • Oxygen delivery (DO2) (mL/min) = cardiac output (CO) × blood oxygen content GRAPHS/ FIGURES

Oxygen–hemoglobin dissociation curve

REFERENCES

1. aw R, Biukwirwa H. The physiology of oxygen delivery. Update Anaesth. 1999;10(3):1–2. 2. reacher DF, Leach RM. Oxygen transport. BMJ. 1998;317(7168):1302–1306.

3. abrales P, Martini J, Intaglietta M, et al. Blood viscosity maintains microvascular conditions during normovolemic anemia independent of blood oxygen-carrying capacity. Am J Physiol Heart Circ Physiol. 2006;291(2):H581–H590. Anand IS. Heart failure and anemia: Mechanisms and pathophysiology. Heart Fail Rev. 2008;13:379–386. 4. Martin L. The four most important equations in clinical practice. Available at: http://www.globalrph.com/martin_4_most2.html

ADDITIONAL READING

• Bartsch P, Saltin B. General introduction to altitude adaptation and motion sickness. Scand J Med Sci Sports. 2008;18(Suppl 1):1–10. • Henig NR, Pierson DJ. Mechanism of hypoxemia. Respir Care Clin N Am. 2000;6(4):501– 521. • Ouellette DR. The impact of anemia in patients with respiratory failure. Chest. 2005;128(5 Suppl 2):576S–582S.

See Also (Topic, Algorithm, Electronic Media Element) • Blood substitutes • Isovolemic hemodilution • Mixed venous oxygen saturation

CLINICAL PEARLS

• Pulse oximetry is not a reliable monitoring modality in the presence of dyshemoglobins (hemoglobin that is unable to bind to oxygen). The 2 major dyshemoglobins seen in clinical practice are carboxyhemoglobin (COHb) and methemoglobin (MetHb). Co-oximeters are able to separate out oxyhemoglobin from MetHb and COHb and are therefore more accurate for quantifying oxygen-carrying capacity/content. • Blood substitutes: Include hemoglobin-based oxygen carriers (HBOCs) which transport oxygen when introduced intravenously. Synthetic analogs, such as perfluorocarbon emulsions (PFCs), have also been used as substitutes. These chemicals are able to dissolve large amount of gases such as oxygen. Unlike blood, PFCs exhibit a linear oxygen dissociation curve with an increase in PaO2 enhancing oxygen transport by these molecules and increasing the driving pressure of diffusion of oxygen into tissues. With a linear relationship however, the need for oxygen remains greater since most of the oxygen is released prior to the arrival of the oxygen-laden molecule to the capillary network where the partial pressure of oxygen is low. These also require high FiO2 to dissolve adequate

amounts of oxygen. However, optimal oxygen transport still remains difficult to reproduce and continues to differentiate real blood from blood substitutes and volume expanders.

BLOOD PRESSURE Mitesh Patel, MD Lydia A. Conlay, MD, PhD

BASICS DESCRIPTION

• Blood pressure (BP) is the pressure exerted by circulating blood upon the walls of blood vessels and is one of the principal vital signs. • During each heartbeat, BP varies between a maximum (systolic) and a minimum (diastolic) pressure. • The mean BP is a function of pumping by the heart and resistance to flow in blood vessels; it decreases as the circulating blood moves away from the heart through arteries (1,2).

PHYSIOLOGY PRINCIPLES

• Mean arterial pressure (MAP) is the average pressure over a cardiac cycle and is determined by the cardiac output (CO), systemic vascular resistance (SVR), and central venous pressure (CVP); it can be calculated by the equation MAP = (CO × SVR) + CVP. • Pulse pressure (PP) is the difference between systolic and diastolic BP which results from the pulsatile nature of cardiac output. PP = SBP − DBP. • BP regulation is modulated by several reflexes on a minute-to-minute basis. – Arterial baroreflex is mediated by stretch-sensitive sensory nerve endings located in the carotid sinuses and the aortic arch. The rate of firing of these baroreceptors increases with arterial pressure, and the net effect is a decreased sympathetic outflow, resulting in decreased arterial pressure and heart rate. – The renin–angiotensin–aldosterone system contributes to the regulation of arterial pressure primarily via the vasoconstrictor properties of angiotensin II and the sodiumretaining properties of aldosterone (3). – Chemoreceptors located in the carotid and aortic bodies regulate BP by monitoring blood pO2, pCO2, and pH. • Diastolic BP plays an important role in coronary perfusion pressure. Coronary perfusion pressure (CPP) is the difference between the aortic diastolic pressure and left ventricular end-diastolic pressure (LVEDP). CPP = DBP − LVEDP. • Manual intermittent measurement techniques: Auscultation remains the most widely used and was originally described by Nikolai Korotkoff in 1905. A sphygmomanometer, cuff, and stethoscope measure BP by auscultating sounds generated by turbulent arterial flow beyond the partially occluding cuff. The first sound is heard at the systolic pressure (phase I). Its character progressively changes (phases II and III), becomes muffled (phase IV), and is finally absent (phase V). Diastolic pressure is recorded at phase IV or V. • Automated intermittent measurement techniques: Most automated noninvasive BP devices are based on oscillometry, where variations in cuff pressure resulting from arterial pulsations during cuff deflation are sensed. The pressure at which the peak amplitude of

arterial pulsations occurs corresponds closely to MAP; systolic and diastolic pressures are derived from proprietary formulas that examine the rate of change of the pressure pulsations. • Direct measurement techniques of arterial BP: Arterial cannulation with continuous pressure transduction and waveform display remains the accepted reference standard for BP monitoring. It is invasive, more costly, and requires technical expertise to perform (4).

DISEASE/PATHOPHYSIOLOGY

• Acute hypertension is a risk factor for myocardial ischemia, stroke, and bleeding from the surgical sites. • Chronic hypertension doubles the risk of cardiovascular disease including coronary heart disease (CHD), congestive heart failure (CHF), ischemic and hemorrhagic stroke, renal failure, and peripheral arterial disease. Because most patients with long-standing hypertension are assumed to have some element of coronary disease and cardiac hypertrophy, excessive BP elevations are undesirable. • Uncontrolled hypertension (>180/120 mm Hg) and/or clinical signs and symptoms of hypertensive emergency warrant cancellation of elective surgery until the BP is optimized. Patients should receive emergency medical care and not simply be sent home. Warning signs and symptoms of hypertensive emergency include: – Headache – Confusion – Visual changes – Seizures – Focal neurologic changes – Nausea and vomiting – Papilledema – Exudative hemorrhages – Shortness of breath – Chest pain – Azotemia, oliguria, and proteinuria

PERIOPERATIVE RELEVANCE

• In the operative setting, systolic and diastolic pressures should generally be kept within 10– 30% of preoperative levels (5). • The systolic BP (generated from myocardial ventricular contraction) helps estimate the risk for a heart attack or stroke according to the Framingham study. Intraoperatively, systolic BP correlates with the amount of surgical bleeding. • MAP is commonly referred to during cardiac surgery (particularly during bypass) and is a determinant of cerebral perfusion pressure (CPP = MAP – ICP). Cerebral blood flow is autoregulated between MAPs of 60 and 180 mm Hg; should the MAP fall below 60 mm Hg, the cerebral blood flow becomes severely decreased. In hypertensive patients, the autoregulation curve is shifted to the right (6). • Severe intraoperative hypotension is an anesthetic emergency, and treatment is vital to ensure adequate organ blood flow, particularly to the brain, heart, kidneys, and the placenta in pregnancy. Consequences of hypotension can include stroke, myocardial infarction, acute

tubular necrosis, fetal compromise, acidosis, and death. Because hypotension can be harmful, this symptom is often treated before the cause has been ascertained. Hypotension can result from abnormalities in preload, contractility, afterload, heart rate, cardiac rhythm, intravascular volume, or SVR. Common causes of hypotension include: – Hypovolemia can reduce preload and may be due to hemorrhage, vomiting, diarrhea, burns, or sepsis. – Increased intrathoracic pressure, as seen with positive pressure ventilation and tension pneumothorax, can reduce preload. – Spinal and epidural anesthesia cause vasodilatation and decreased preload due to sympathetic block; if the block is above T4, it may also result in decreased myocardial contractility and bradycardia. – Excessive anesthesia: General anesthetics (both inhalation and intravenous) may cause hypotension by reducing CO and SVR. – Obstruction of major vessels can increase afterload and cause pump failure. Causes include pulmonary embolism or aortocaval compression by tumor or pregnancy. – Decreased myocardial contractility, as from beta-blockers, cardiac arrhythmias, cardiac tamponade, and myocardial infarction – Bradycardia, as from heart block or vagal overtone – Shock, as from spinal, cardiogenic, or anaphylaxis shock or sepsis • Treatment of intraoperative hypotension often precedes treating the cause: – Optimize preload: Administer an intravenous fluid bolus. – Elevate legs or head down tilt to improve venous return. – Reduce anesthetic agent if appropriate. – Use sympathomimetic drugs. • Causes of intraoperative hypertension include: – “Light” anesthesia or pain – Hypercarbia – Medication error (inadvertent administration of pressors) – Preeclampsia/eclampsia – Acute increase in intracranial pressure – Volume overload – Full bladder – Pheochromocytoma – Autonomic hyperreflexia – Decreased vascular compliance (arteriosclerosis) – Disorders with increased cardiac output (aortic regurgitation, thyrotoxicosis) – Renal parenchymal diseases – Aortic coarctation – Medications (such as monamine oxidase inhibitors, cocaine, or methamphetamine) • Autonomic hyperreflexia or dysreflexia (AD) is a life-threatening condition which occurs most often in individuals with spinal lesions above the T6 spinal cord level. At this level, the lesion is cephalad to the sympathetic cell bodies in the spinal cord and is believed to disrupt descending CNS impulses that normally regulate sympathetic outflow. AD is a reaction of the autonomic (involuntary) nervous system to overstimulation which is characterized by

severe hypertension, (reflex) bradycardia, profuse sweating, vasodilation above the level of the lesion (including flushing of the skin, nasal stuffiness, severe headaches), apprehension, anxiety, and occasionally cognitive impairment. AD is believed to be triggered by afferent stimuli originating below the level of the lesion, which increase BP via sympathetically mediated vasoconstriction in muscle, skin, and splanchnic vascular beds (7). The stimuli that trigger AD often result from the distension of a viscous such as the bladder or intestine.

GRAPHS/FIGURES See Table See Table

REFERENCES 1.

Health and Life. Normal blood pressure range adults. Available http://healthlifeandstuff.com/2010/06/normal-blood-pressure-range-adults/ 2. labunde R. Cardiovascular physiology concepts. Lippincott Williams & Wilkins, 2005.

at:

3. Klabunde RE. Cardiovascular physiology concepts: Mean arterial pressure. Available at: http://www.cvphysiology.com/Blood%20Pressure/BP006.htm [Accessed September 29, 2008; Archived version October 3, 2009. 4. Karlsson AK. Autonomic dysreflexia. Spinal Cord. 1999;37:383–391. 5. Rohrig R, Junger A, Hartmann B, et al. The incidence and prediction of automatically detected intraoperative cardiovascular events in noncardiac surgery. Anesth Analg. 2004;98(3):569–577.

ADDITIONAL READING

• Morgan GE, Mikhail MS, Murray MJ. Anesthesia for patients with cardiovascular diseases. In: Clinical Anesthesiology, 4th ed., McGraw Hill, 2005, chapter 20.

See Also (Topic, Algorithm, Electronic Media Element) • Autonomic hyperreflexia • Controlled hypotension • Arterial waveform • Perioperative hypertension • Mean arterial pressure

CLINICAL PEARLS

• Maintaining an adequate BP is essential to maintain perfusion to vital organs. BP should be maintained within 10–30% of the patient’s baseline. • The consequences of hypotension are sufficiently serious to potentially warrant treatment even before the cause of the hypotension is ascertained. Intraoperative hypotension most commonly reflects “deep” anesthesia, hypovolemia, or the use of specific drugs or anesthetic techniques. • Uncontrolled hypertension is associated with an increase in perioperative morbidity and

mortality. Elective cases should be cancelled when a patient demonstrates signs of a hypertensive emergency. Anesthesiologists are often faced with the decision to cancel or proceed with uncontrolled BPs exceeding 180/110 mm Hg. • Titrating therapies to traditional endpoints such as blood pressure does not ensure that the microvascular bed is being adequately perfused. For example, a normal or high blood pressure may be a vasoconstrictive response to a low cardiac output state.

BLOOD SUBSTITUTES Jonathan S. Jahr, MD Dayna Zimmerman, BS

BASICS DESCRIPTION

• “Blood substitutes” have been studied for >50 years and are either derivatives of hemoglobin or perfluorocarbons; they are designed to carry and offload oxygen to tissues. – Hemoglobin-based oxygen carriers are termed (HBOCs); attained from human or bovine sources. – Perfluorocarbon-based oxygen carriers are termed (PFBOCs). • No products discussed are FDA approved for human use. One product (Hemopure®, OPK Biotech, Cambridge, MA) has been approved in South Africa and Russia. Another product (Oxyglobin®, OPK Biotech) is FDA and European Union approved for canine anemia. PHYSIOLOGY PRINCIPLES

• Blood substitutes have been designed to carry oxygen to ischemic tissue as well as tested as a resuscitation fluid. • HBOCs are: – Synthesized from human or bovine blood cells in a process that removes the red cell membrane, purifies and deactivates pathogens (prions), and re-polymerizes the purified hemoglobin (via glutaraldehyde pegylation, encapsulation, or zero-link polymerization). – Prepared as a bag of solution around 250–500 mL, or the equivalent amount of hemoglobin as a unit of packed red blood cells. Some of the HBOCs offload oxygen more easily and may be more efficient than banked blood. – Newer generations have attempted to link oxygen carrying with diminished extravasation from the vascular compartment, block nitric oxide scavenging, and serve as antiinflammatory agents to diminish the deleterious effects of ischemia. • “First-generation” HBOCs are designed to have a normal hemoglobin (10–13 g/dL), normal viscosity, elevated colloid oncotic pressure, shift the oxyhemoglobin dissociation curve to the right, and a normal Hill coefficient. – They include α-α cross-linked hemoglobin, 2,3 diaspirin cross-linked hemoglobin (HemAssist®, Baxter, Deerfield, IL), and hemoglobin raffimer (Hemolink™, Hemosol, Toronto, ON). • “Second-generation” HBOCs are designed with the same goals as first-generation HBOCs but with fewer side effects. They too have a normal hemoglobin (10–13 g/dL), normal viscosity, elevated colloid oncotic pressure, shift the oxyhemoglobin dissociation curve to the right, and a normal Hill coefficient. To date, they remain the most successful HBOCs. – Human polyhemoglobin (PolyHeme®, Northfield, Evanston, IL) and hemoglobin glutamer (bovine) 200 and 250 (Hemopure® and Oxyglobin®, OPK Biotech) have completed FDA Phase III testing but were not approved in the US.

• “Third-generation” HBOCs have a low hemoglobin (5–6 g/dL), normal to high viscosity, lower colloid oncotic pressure, shift the oxyhemoglobin dissociation curve to the left, and a normal Hill coefficient. – There are a number of “third-generation” HBOCs currently undergoing preclinical and clinical testing (Maleimide-Polyethylene Glyco-modified Hemoglobin [MP4], Hemospan®, Sangart, San Diego, CA; Zero-linked Hemoglobin Polymer Oxyvita®, OXYVITA, New Windsor, NY).

DISEASE/PATHOPHYSIOLOGY

• “First-generation” HBOCs had serious complications including renal failure and increased mortality in trauma trials (HemAssist®). • “Second-generation” HBOCs cause increased systemic and pulmonary blood pressure, increased lipase without clinical signs or symptoms of pancreatitis, and transient jaundice, secondary to breakdown of the hemoglobin by the reticuloendothelial system. • “Third-generation” HBOCs may avoid the hypertension, but may still have other complications. • In one study, elderly patients tended to have worse outcomes with the particular blood substitute, suggesting that patients with pre-existing hypertension, cardiac, renal, and cerebrovascular disease may be susceptible to the hypertensive effects.

PERIOPERATIVE RELEVANCE

• The concept of blood substitutes is attractive in that they are: – Stable at room temperature – Do not require cross-matching and are immediately available – Do not carry infectious disease risk – Not dependent on a limited donor supply • Possible indications for blood substitutes include: – Shock – Organ ischemia – Red blood cell incompatibility – Acute lung injury – Transplant organ preservation – Cardioplegia – Sickle cell anemia – Tumor therapy – Air embolism – Anemia refractory to allogenic blood transfusion – Emergency civilian or military setting of severe trauma or perioperative bleeding • Allogenic blood transfusions have multiple risks, including infectious, immunologic, metabolic, and critical illnesses. – Screening of blood has reduced the incidence of HIV and Hepatitis C; however, new infections take time to be detected and removed from the donor supply. – Immunomodulation can result in increased surgical wound infection and recurrence of cancer (especially colon cancer) as well as decreased graft survival of transplanted organs.

– Transfusion-related acute lung injury (TRALI) can occur in 1:5,000 transfusions and carries a high mortality ranging from 6% to 9%. – Transfusion reactions from laboratory or transfusion error can result in serious morbidity and mortality. – Metabolic derangements include hypothermia, hyperkalemia, and decreased 2,3-DPG. – Transfusion-associated circulatory overload (TACO) is due to rapid transfusion of a large volume of blood and can cause dyspnea, orthopnea, peripheral edema, and rapid increases in blood pressure. It carries an incidence of 1:100–10,000. – However, even if a blood substitute is developed and has minimal complications, blood donation cannot be replaced; donor blood is fractionated to multiple products including platelets, fresh frozen plasma, and cryoprecipitate.

GRAPHS/FIGURES

Hypothesized Mechanism of Action

Nitric Oxide (NO) Scavenging of Hemoglobin

REFERENCES

1. Jahr JS, Walker V, Manoochehri K. Blood substitutes as pharmacotherapies in clinical practice. Curr Opin Anaesthesiol. 2007;20:325–330. 2. ahr JS, Moallempour M, Ellis JE. Transfusion update—triggers, targets, and will we ever have a blood substitute? Curr Rev Clin Anesth. 2008;28(21):249–260. 3. Jahr JS, Moallempour M, Lim JC. HBOC-201, Hemoglobin glutamer 250 (bovine), Hemopure® (Biopure Corporation, Cambridge, MA). Expert Opin Biol Ther. 2008;8(9):1425–1433. 4. Jahr JS, Mackenzie C, Pearce B, et al. HBOC-201 as an alternative to blood transfusion: Efficacy and safety evaluation in a multicenter phase III trial in elective orthopedic surgery. J Trauma Injury Infect Crit Care. 2008;64(6):1484–1497. http://www.nhlbi.nih.gov/health/dci/Diseases/bt/btrisk.html • Jahr JS, Sadighi Akha A, Doherty L, et al. Hemoglobin-based oxygen carriers: History, limits, brief summary of the state of the art, including clinical trials. In: Mozzarelli A, Bettati S. Chemistry and biochemistry of oxygen therapeutics: From transfusion to artificial blood.

London: John Wiley and Sons Ltd, 2011, chap. 22.

See Also (Topic, Algorithm, Electronic Media Element) • Blood transfusion • Blood transfusion infectious risks

CLINICAL PEARLS

• Ideally, blood substitutes could benefit patients who refuse allogenic blood transfusions, trauma patients (military or civilian) for whom blood is not easily available, patients who are unable to receive allogenic blood for immunologic reasons (hemolytic anemia), and to augment acute normovolemic hemodilution. • Side effects of blood substitutes that limit their use include: • Vasoactivity • Nephrotoxicity • Interference with complement • Mononuclear phagocytic system activation • Histamine release • Antigenicity • Oxidation in storage • Activation of kinin and coagulation • Iron deposition • Lack hemoglobin’s ability to scavenge nitric oxide • At this time, there are no FDA-approved products available for human use.

BONE MARROW TRANSPLANT (HARVEST PROCEDURE) Lori Dangler, MD, MBA

BASICS DESCRIPTION General

• Bone marrow transplants (BMT) are used to help patients with various kinds of serious illnesses: – Marrow failure (aplastic anemia) – Hematologic malignancy (AML, ALL, CML, CLL, myeloma) – Selected chemotherapy-responsive solid tumors (lymphoma, Hodgkin’s, non-Hodgkin’s) – Immunodeficiency syndromes – Other genetic disorders • Bone marrow harvesting and transplantation procedures were first developed in the 1950s and the first successful bone marrow transplantation occurred in 1968. • Spaces in the bone marrow hold both blood and stem cells. Stem cells are multipotent hematopoietic cells that have the ability to grow into various types of future blood cells. • During a harvest, a small portion of marrow is collected to be used for transplantation. Multiple large-bore needle aspirations of marrow are taken from the posterior iliac crests. At the end of the procedure, aspiration sites are cleaned and covered with pressure dressings. • Transplantation terms: – Autologous BMT is when one has marrow harvested and frozen for future use. – Allogenic BMT is when marrow is harvested for a relative. – Syngeneic BMT is harvested for an identical twin. – Unrelated BMT is when there is a donation through the registry. • Marrow donor patient types: – Autologous: Patients with malignancies who respond to chemotherapy (should be free of active disease and have functioning bone marrow) – Allogenic: HLA-matched healthy donors (often related) for recipient with malignancy or marrow failure Position

• Supine for intubation, then prone • Prep around iliac crests

Incision

• Operating physician is often a hematologist. • Large-bore needle insertion into the posterior iliac crests (other sites less common)

Approximate Time 1–2 hours

EBL Expected

• 1–2 quarts of bone marrow are commonly collected from adults. • Cell count of marrow determines volume needed (1–4 × 108 cells/kg recipient body weight).

Hospital Stay

• Outpatient to overnight maximum (healthy donors) • Prolonged hospitalization for autologous donors/future recipients with anticipated support for anemia, thrombocytopenia, neutropenia, and graft versus host issues

Special Equipment for Surgery

• Bone marrow aspiration needles • Collection bags • Padding/chest rolls/head support for prone positioning • Pathologist on standby to determine the cell count

EPIDEMIOLOGY Incidence

• 950 transplants were performed using bone marrow during 2010. – Children (0–17 years) received 21% of transplants. – Adults 18–50 years received 38% of transplants. – Adults >50 years received 41% of transplants.

Prevalence

15,000 people in the US are diagnosed with life-threatening illnesses yearly where a BMT or cord blood transplant from a matched donor is their best treatment option. Morbidity

• Autologous donor: Postoperative morbidity ranges from moderate to high secondary to underlying malignancy. • Allogenic: Life-threatening complications are extremely rare (0.27%) for healthy donors.

Mortality

• Rare • Between 1993 and 2005, there were 27,770 first BMTs, with only 1 fatal event (pulmonary embolism) reported and 12 serious adverse events were observed. The most frequent adverse events were cardiac (European Group for Blood and Marrow Transplantation analysis).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Familiarity with the patient’s specific chemotherapy. Avoid unnecessary oxygen enrichment if the patient had Bleomycin. • Avoid nitrous oxide since it inhibits methionine synthetase. • Volume status and blood loss assessment; replacement with crystalloids, albumin, and irradiated products

• Prior steroid therapy usage can lower adrenal reserves. • Careful positioning to avoid prone position-related injuries

PREOPERATIVE ASSESSMENT SYMPTOMS

• Healthy donor may be asymptomatic. • Assessment points apply primarily to autologous donors. – GI: Vomiting, diarrhea, melena

History

When autologous harvesting, attain a thorough history of underlying disease, complications of chemotherapy (e.g., pericardial effusion, impaired cardiac function), and presence of infection. Signs/Physical Exam

• CV: Focused exam to assess for congestive heart failure (jugular venous distention, pitting edema, murmurs, rales or crackles) • Peripheral: Edema, orthostasis • Heme: Ecchymosis, petechiae

MEDICATIONS

• Iron supplementation • Erythropoietin • Granulocyte colony stimulating factor (Filgrastim, Pegfilgrastim) • Chemotherapy; last dosage

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Urinalysis to rule out urinary tract infections • Electrolytes if recent chemotherapy • CBC for platelets, hemoglobin (baseline) • Coagulation profile if bleeding history • ECG, echocardiogram, and/or stress testing if there is a concern for cardiac dysfunction • Type and cross for 2 units irradiated blood if autologous donation was not performed

CONCOMITANT ORGAN DYSFUNCTION

Autologous donors: Prior chemoradiation treatments resulting in temporary/permanent organ dysfunction

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines • Opioids • Steroid coverage

Special Concerns for Informed Consent Blood transfusion highly probable INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal most common used for prone positioning • Neuraxial block with a spinal or epidural may be appropriate if the patient is hydrated and without coagulopathies

Monitors

• Minimum of 2 large-bore IVs; central line access may be considered if venous access is difficult. • Foley catheter if large fluid shifts and replacement are anticipated • Arterial access may be useful if the BP is labile. • Monitor ETCO2 closely; an acute drop may indicate marrow embolism (dead space pathophysiology).

Induction/Airway Management

• Consider lower doses of induction agent when there is a history of orthostasis and cardiotoxic chemotherapy use. • Endotracheal tube provides a secure airway.

Maintenance

• After induction of anesthesia, establish prone positioning and careful padding of pressure points. • Heparin is administered pre-harvest. • The total volume of marrow harvested is dependent on the body mass of the recipient as well as the cellularity of the donor marrow. The target number of donor stem cells for allogenic engraftment of unmanipulated marrow is 2–3 × 108 nucleated marrow cells/kg. • If the patient requires a pRBC transfusion, irradiated units should be administered to avoid potential engraftment of random donor nucleated cells.

Extubation/Emergence

Return to supine position for extubation

POSTOPERATIVE CARE BED ACUITY

• Often performed on an outpatient basis • Most donors are admitted to a same-day surgical unit on the morning of donation (volume status changes).

• PACU monitoring is typically for 1–2 hours. • Check pressure dressing on back • May need transfusion; most donors will store 1–2 units of autologous blood.

ANALGESIA

• Local anesthetic at harvest puncture sites • Tylenol with codeine • Consider NSAIDs such as ketorolac if the patient is not coagulopathic.

COMPLICATIONS

• Pain is the most common complication of bone marrow harvesting and results from trauma of the iliac bones and overlying soft tissue. • Anemia • Transfusion-related complications • Fever • Orthostasis • Vomiting • Bleeding/hematoma • Infection • Compressive neuropathies (should resolve with reabsorption of the hematoma) • Anesthesia-related complications

REFERENCES

1. Bolwell BJ, Maurer W, Anderson J, et al. Outpatient bone marrow harvest: The Cleveland Clinic experience. Bone Marrow Transplant. 1995;16(5):703–705. 2. Borton MM, Buckner CD. Major complications of marrow harvesting for transplantation. Exp Hematol. 1983;11:916–921. 3. Bosi A, Bartolozzi B. Safety of bone marrow stem cell donation: A review. Transplant Proc. 2010;42(6):2192–2194. 4. Buckner CD, Clift RA, Sanders JE, et al. Marrow harvesting from normal donors. Blood. 1984;64:630–634. 5. Burmeister MA, Standl T, Brauer P, et al. Safety and efficacy of spinal vs. general anaesthesia in bone marrow harvesting. Bone Marrow Transplant. 1998;21(11):1145– 1148. 6. Chern B, McCarthy N, Hutchins C, et al. Analgesic infiltration at the site of bone marrow harvest significantly reduces donor morbidity. Bone Marrow Transplant. 1999;23:947–949. 7. Filshie J, Pollock AN, Hughes RG, et al. The anaesthetic management of bone marrow harvest for transplantation. Anaesthesia. 1984;39(5):480–484. 8. Jin NR, Hill RS, Petersen FB, et al. Marrow harvesting for autologous marrow transplantation. Exp Hematol. 1985;13(9):879–884. 9. Knudsen LM, Johnsen HE, Gaarsdal E, et al. Spinal versus general anaesthesia for bone marrow harvesting. Bone Marrow Transplant. 1995;15(3):486–487.

10. Lederhaas G, Brock-Utne JG, Negrin RS, et al. Is nitrous oxide safe for bone marrow harvest? Anesth Analg. 1995;80(4):770–772.

11. Machaczka M, Kalaitzakis E, Eleborg L, et al. Comparison of general vs. regional anaesthesia for BM harvesting: A retrospective study of anaesthesia-related complications. Bone Marrow Transplant. 2010;45(1):53–61. 12. Miller JP, Perry EH, Price TH, et al. Recovery and safety profiles of marrow and PBSC donors: Experience of the National Marrow Donor Program. Biol Blood Marrow Transplant. 2008;14(9 Suppl):29–36.

13. Stein RA Jr, Messino MJ, Hessel EA 2nd. Anaesthetic implications for bone marrow transplant recipients. Can J Anaesth. 1990;37(5):571–578. 14. Stroncek DF, Holland PV, Bartch G, et al. Experiences of the first 493 unrelated marrow donors in the National Marrow Donor Program. Blood. 1993;81:1940–1946.

15. Thorne AC, Malbin KF, Jain M, et al. Autologous bone marrow harvesting in outpatients. J Clin Anesth. 1996;8(7):551–556. 16. Thorne AC, Stewart M, Gulati SC. Harvesting bone marrow in an outpatient setting using newer anesthetic agents. J Clin Oncol. 1993;11(2):320–323. 17. Vanhelleputte P, Nijs K, Delforge M, et al. Pain during bone marrow aspiration: Prevalence and prevention. J Pain Symptom Manage. 2003;26(3):860–866. See Also (Topic, Algorithm, Electronic Media Element) • Blood transfusion

CODES ICD9 • V42.81 Bone marrow replaced by transplant • V59.3 Bone marrow donors ICD10 • Z52.3 Bone marrow donor • Z94.81 Bone marrow transplant status

CLINICAL PEARLS

• Patients should hold aspirin or aspirin-containing compounds for 10 days prior to the procedure; ibuprofen and ibuprofen-containing compounds should be held for 3 days prior. • The procedure is performed under sterile conditions to avoid infection; autologous harvests may involve immunocompromised patients.

BOWEL RESECTION/COLECTOMY Dmitri Bezinover, MD, PhD Priti G. Dalal, MD, FRCA

BASICS DESCRIPTION General

• Small bowel and colon resections are performed for elective and acute abdominal conditions and may be performed either open or laparoscopically. – Elective indications include tumors, diverticulitis or diverticulosis, Crohn’s disease, ulcerative colitis, angiodysplasia, familial adenomatous polyposis, radiation enteritis, and intestinal fistula. – Acute conditions include bowel or colon obstruction or perforation, mesenteric infarction, bleeding, volvulus, intussusception, and trauma. – Laparoscopy has the advantage of decreased pain, earlier return of GI functions, and quicker discharge from the hospital. However, it can be technically challenging, or may not be appropriate in coagulopathic or acute abdomens. • Bowel resections involve identifying, mobilizing, and confining the affected bowel. Bowel clamps are applied proximally and distally to the site and then resected. – Re-anastomosis is performed by one of the following techniques: Open end-to-end, closedend-to-end, stapled, or functional end-to-end. – Stomas are created when inflammation is present to allow time to heal. – Colon resection procedures include right or left hemicolectomies, sigmoid colectomies, and total colectomies. – Malignant disease processes can involve the removal of lymph nodes or mesentery. Incision

Vertical or transverse depending on the procedure Approximate Time

Variable—may increase with adhesions, obesity, or “re-do” abdomen EBL Expected

Variable—may increase with proximity to vascular structure, vascularity of malignancy, or inadvertent vessel penetration Hospital Stay

2–5 days; based upon return of bowel function, perioperative complications, and comorbidities Special Equipment for Surgery

Laparoscopic equipment as appropriate EPIDEMIOLOGY Prevalence

Acute abdomen: Bowel obstruction 0.13%; mesenteric infarction 0.3–8.5%; bowel/colon perforation 1.8–4.1% Prevalence

Increases with age and a family history Morbidity

Complications associated with resection: Ileus <10%; atelectasis 10%; anastomosis insufficiency of the small bowel <3%, colon 2–4%; wound infection small bowel repair <5%, colon repair 4–10%; splenic injury following colon resection 1%; and bleeding 1% Mortality

• Major cause is anastomosis insufficiency with subsequent sepsis. • Small bowel resections 1–5%; colon resection 0.5–2% • Acute conditions >20% • Gangrenous mesenteric infarction 60–70%

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Fluid and electrolyte deficits can be dramatic; aggressive hydration and replacement of electrolytes need to take place while concurrently reassessing the patient’s volume status. • Increased intra-abdominal pressures from the underlying disease process, surgical retractors and packing, or Trendelenburg position result in decreased FRC and lung compliance. High PIP and PEEP can be necessary. • Hemodynamic instability may occur with exposure, manipulation of the bowel, onset of sepsis, or hypovolemia.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Dependent upon the location of bowel disease • Pain • Nausea and vomiting • Diarrhea or constipation

History

• Bowel prep • Recent weight loss • Anticoagulants that would preclude epidural placement

Signs/Physical Exam

• Signs of dehydration: Vital signs; decreased skin turgor, capillary refill, or urinary output

• Signs of electrolyte abnormalities: ECG changes or muscle weakness • Signs of sepsis: Fever, tachycardia, or hypotension

MEDICATIONS

• H2 blockers or proton pump inhibitors

• Stool softeners • Anti-inflammatories, steroids • Chemotherapy • Acute abdomen: Intravenous fluids, vasopressors, antibiotics, and electrolyte replacement

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC to assess for anemia, infection, thrombocytopenia, or thrombocytosis (acute phase reactant) • Coagulation profile • Electrolytes • Chest radiograph may be indicated when pulmonary comorbidities exist. • Abdominal radiograph for the evaluation of free air under the diaphragm

CONCOMITANT ORGAN DYSFUNCTION Age-related diseases

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis as needed • Metoclopramide, antacids, H2 blockers prior to induction for full stomach. Promotility agents are contraindicated in bowel obstruction and perforation. • Nasogastric (NG) tube placement may be indicated. • Blood transfusion may be considered for anemia.

Special Concerns for Informed Consent

• Epidural catheter placement for postoperative pain management; the potential benefits should be discussed. • Blood transfusion • Central line access may be needed in acute abdomens. • Postoperative ventilation, particularly in acute abdomens

Antibiotics/Common Organisms

• Elective bowel resections: – Coverage for Gram-positive cocci and Gram-negative coccobacilli: First- and secondgeneration cephalosporins; second generation provide better Gram-negative coverage.

• Colorectal procedures: – Additional coverage of anaerobes: First- and second-generation cephalosporins combined with metronidazole – Resistance or allergies, consider gentamicin or imipenem combined with metronidazole

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia is typically performed for open and laparoscopic procedures; this allows for a secure airway, as well as the ability to provide positive pressure ventilation and profound muscle relaxation. • Epidurals (T8–T10 placement) for postoperative analgesia combined with a general anesthetic have the potential benefit of reduced blood loss during surgery, lower extremity venous stasis and thrombosis, atelectasis and hypoxia; improved analgesia; and quicker return of bowel function and time to ambulation. Epidurals are not typically utilized for laparoscopic resections; however, if there is a reasonable possibility of converting to an open procedure, it may be considered. Contraindications include sepsis, coagulopathy, or acute abdomen. • Epidural for surgical anesthesia with monitored anesthesia care (MAC) may be considered when the incision is below the umbilicus. This is not typical, but may be considered when intubation and mechanical ventilation or general anesthesia could have untoward effects (i.e., pulmonary cripples, postoperative delirium).

Monitors

• ASA standard monitors • Nerve stimulator • 2 large-bore IVs; central line access may be warranted in emergent cases for acute abdomens. • Invasive monitors (arterial line, central line, pulmonary artery catheter, TEE) are based upon comorbidities, extent of surgery, and perioperative hemodynamic disturbances.

Induction/Airway Management

• Rapid-sequence induction (RSI) may be indicated for bowel obstruction, bowel motility impairment, or peritoneal irritation. – If an NG tube is in place, it should be suctioned to reduce the risk, or volume, of aspiration. – Induction agents should take into account volume status and comorbidities. Propofol may cause profound hypotension; etomidate or ketamine may be considered. – Neuromuscular blocking agents: Succinylcholine 1–1.5 mg/kg or rocuronium bromide 0.6–1.2 mg/kg – Narcotics may be withheld in patients with a potentially difficult airway or hemodynamic impairment.

Maintenance

• Balanced anesthetic – Volatile or total intravenous anesthesia plus epidural anesthesia; minimal to no

intravenous opioids – Volatile or total intravenous anesthesia combined with intravenous opioids • Nitrous oxide is typically avoided since it can cause bowel distention. • Muscle relaxation allows for adequate retraction and prevents bowel extrusion. • Mechanical ventilation: Patients can have decreased pulmonary compliance and FRC from the underlying bowel disease, as well as surgical maneuvers (e.g., retractors, packing, Trendelenburg). Inspiratory flows, I:E ratios, respiratory rate, and ventilation mode (pressure versus volume control) may need to be adjusted. • Epidural infusion with a local anesthetic and opioid is commonly utilized in open procedures. – Local anesthetics: Bupivacaine (0.125–0.5%) or ropivacaine (0.1–0.2%) – Opioids: Fentanyl (1–5 mcg/mL) or hydromorphone (10 mcg/mL) – Infusion rate usually ranges from 4 to 12 mL/hr. – Boluses often range from 2 to 6 mL. – Doses and rates should be reduced in hypotension. • Fluid and blood management – Crystalloids: In acute cases, the patient may require significant volumes as high as 10–15 mL/kg/hr. Laparoscopic cases have less insensible losses. – Colloids, such as albumin or hetastarch, may be utilized. Hetastarch may not be appropriate in patients with known renal disease and/or coagulopathies. – Blood transfusion may be indicated to increase the oxygen-carrying capacity. • ABG monitoring: Aids in the diagnosis, assessment of severity, and response to therapy for metabolic acidosis • Stress dose steroids should be considered in patients who have taken high-dose steroids for 2 weeks within the past 6–12 months. The administered steroid should have glucocorticoid and mineralocorticoid activity. • Avoid hypothermia: Bowel exposure and cold fluid administration can result in radiation and evaporation of heat to the environment. – Upper and lower body warming blankets, underbody fluid blanket, and fluid warmers can reduce heat loss and facilitate warming. – Hypothermia can result in delayed awakening, arrhythmias, impaired myocardial contractility (and hypotension), coagulopathy, prolonged ventilation, and postoperative wound infection. • DVT prophylaxis includes intermittent pneumatic compression devices, anti-embolism stockings, low-dose unfractionated heparin, LMWH as per institution protocol. • Antiemetic prophylaxis: Abdominal procedures may have an increased incidence of postoperative nausea and vomiting.

Extubation/Emergence

• Muscle relaxation is often needed to facilitate closure; careful titration and twitch monitoring can help achieve this effect without compromising the ability to reverse the patient at the end of the case. • Extubation criteria are the same for elective and acute surgery. However, in acute surgery, the patient may be less capable of meeting the criteria. – Ensure adequate reversal of muscle relaxants

– Carefully assess for extubation criteria in acute abdomens; consider performing an ABG. Additionally, take into account other organ systems and the potential to return to the operating room in the near future.

FOLLOW-UP BED ACUITY

• Elective cases can often be discharged to the floor; comorbidities or intraoperative events may require increased acuity. • The ICU is often appropriate for acute procedures.

ANALGESIA

Epidural analgesia: Continue infusion with a long-acting local anesthetic combined with an opioid, blood pressure permitting. COMPLICATIONS

• Anastomosis insufficiency, infections, ileus • Hemodynamic instability, thrombosis/embolic events • Atelectasis, hypoxemia • Hemorrhage • Postoperative nausea and vomiting • Rare complications: Postoperative bleeding and surgical site infection after laparoscopic surgery, fistulas, strictures, short bowel syndrome, urethral injures, bladder injures, sexual dysfunction, trapped ovary syndrome PROGNOSIS

Depends on underlying condition

REFERENCES

1. itkenheadAR. Anesthesia and bowel surgery. Br JAnesth.1984;56:95–101. 2. Lund C. Anaesthesia for minimally invasive gastric and bowel surgery. Best Pract Res Clin Anaesthesiol. 2002;16(1):21–33.

ADDITIONAL READING

• Ogunnaike BO, Whitten CW. Gastrointestinal disorders. In:Barash PG, CullenBF, Stoelting RK, etal., eds. Clinical anesthesia. Philadelphia:Wolters Kluwer Lippincott Williams & Wilkins, 2009. See Also (Topic, Algorithm, Electronic Media Element)

• Crohn disease/ulcerative colitis • Colorectal surgery • Fluid management

CLINICAL PEARLS

• Patients presenting for bowel resections can have a myriad of indications. • Emergent procedures for acute processes can be associated with significant fluid and electrolyte imbalances, multiple-organ insults, as well as mortality. • Minimally invasive surgical procedures are increasing in scope.

BRACHIAL PLEXUS ANATOMY Mandip S. Kalsi, MD Nabil Elkassabany, MD

BASICS DESCRIPTION

• The brachial plexus is composed of the anterior primary divisions (ventral rami) of the C5, C6, C7, C8, and T1 nerve roots. • As the plexus travels through the neck into the upper extremity, it divides into roots, trunks, divisions, cords, and branches. There are 5 “terminal” branches and other “collateral” branches that leave the plexus at various points along its length. • An understanding of brachial plexus anatomy is essential for successful placement of regional nerve blocks of the upper extremities, as well as recognizing and minimizing complications, should they occur. PHYSIOLOGY PRINCIPLES

• The building units of peripheral nerves are the “nerve fascicles.” Each fascicle contains numerous nerve fibers and blood vessels within loose connective tissue called the endoneurium. Each bundle of fascicles is separated from one another by a multilayer epithelial sheath (perineurium). The fascicles are held together by an outer connective tissue sheath (epineurium). • Peripheral nerves are mixed nerves; different types of nerve fibers exist within the same nerve and serve different functions (motor, sensory, autonomic). • Each nerve fiber can be classified by size and whether or not it is myelinated. • The ratio of connective tissue to neuronal tissue increases from proximal to more distal locations. • The brachial plexus provides the somatic sensory and motor nerve supply to most of the upper extremity. – Radial nerve (posterior cord) Motor: Extensors of the elbow, wrist, and fingers Sensory: Lateral 3 and ½ fingers on the dorsal side (thumb, index, middle finger, and ½ of the ring finger) minus the proper palmar digital area (finger tips) – Median nerve (both the lateral and medial cords) Motor: Flexors of the forearm and intrinsic muscles of the thumb (thenar muscles) Sensory: Lateral 3 and ½ fingers on the palmar side (thumb, index and middle finger, and ½ of the ring finger) and proper palmar digital on the dorsum (finger tips) – Ulnar nerve (medial cord) Motor: Intrinsic muscles of the hand Sensory: Medial 1 and ½ digits (pinkie, and ½ of the ring finger) dorsal and palmar side – Musculocutaneous nerve (lateral cord) Motor: Flexors of the arm

Sensory: Lateral side of the forearm

ANATOMY

• The nerve fibers leave the intervertebral foramina and join together to form 5 nerve roots that subsequently form 3 trunks, followed by divisions, cords, and several terminal nerves. • Each trunk has 2 divisions that eventually rearrange into 3 cords and several terminal branches. This most common representation occurs only in about 65% of people. There are approximately 39 other variations. • Roots: The ventral rami of the spinal nerves of C5–8 and T1 form the 5 roots of the brachial plexus. The roots emerge from the vertebral foramina between the anterior and posterior tubercle of the transverse process, pass between the anterior and middle scalene muscles, and converge into the 3 trunks. Of note, the transverse process of C7 is characterized by its lack of an anterior tubercle. This feature can be very helpful to distinguish the nerve roots at different levels during ultrasound imaging of the brachial plexus. • Trunks and divisions: The 3 trunks termed superior, middle, and inferior, due to their vertical arrangement in relation to one another, are formed between the anterior and middle scalene muscles. The superior trunk is derived from the C5–6 roots, the middle trunk from the C7 root, and the inferior trunk from the C8–T1 roots. The phrenic nerve lies close to the brachial plexus as it passes over the anterior scalene muscle. As the trunks continue over the first rib and below the mid-portion of the clavicle, each trunk divides into the anterior and posterior divisions. • Cords and branches: As the divisions emerge below the clavicle, the fibers arrange again to form the lateral, medial, and posterior cords that are so named according to their relationship to the axillary artery. The lateral cord is formed from the superior divisions of the superior and middle trunks, the medial cord is a continuation of the anterior division of the inferior trunk, and the posterior cord is formed from the inferior divisions from all 3 trunks. The 3 cords then divide into, and ultimately form, the peripheral nerves of the upper extremity. The lateral cord divides into the lateral head of the median nerve and terminates as the musculocutaneous nerve. The medial cord divides into the medial head of the median nerve, the medial antebrachial, the medial brachial cutaneous, and terminates as the ulnar nerve. Finally, the posterior cord gives rise to the axillary nerve and terminates as the radial nerve.

DISEASE/PATHOPHYSIOLOGY

• Brachial plexus injury can result from excessive stretching or avulsion injury during labor due to shoulder dystocia. Other causes for brachial plexus injury may include shoulder trauma, excessive stretching, and radiation to the neck. The severity of injury depends on the extent of the nerve damage. It ranges from neurapraxia, where there is no interruption of nerve conduction, to complete disruption of the nerve fiber. • Nerve injury during placement of a brachial plexus block may be safeguarded against by: – Having an awake patient who can communicate the sensation of pain and paraesthesia on intraneural injection – Not injecting against high resistance. This may be a sign of intraneural injection. – Utilizing ultrasound imaging. Theoretically, it can decrease the incidence of nerve injury, but this has yet to be demonstrated in the setting of large clinical trials.

– Not injecting local anesthetic at a neurostimulator current intensity of 0.2 mA or less • Systemic toxicity of local anesthetic: All measures should be taken to avoid intravascular injection of local anesthetic. – In an awake patient, monitor for signs/symptoms of toxicity. – Monitor vital signs and EKG. – Intermittently aspirate during injection of the local anesthetic. • Pneumothorax: The proximity of the pleura to the brachial plexus makes this a possibility. Ultrasound techniques have helped revive some of the blocks that were falling out of favor (e.g., supraclavicular block).

PERIOPERATIVE RELEVANCE

• Blocks above the clavicle (mainly the interscalene block and, to a lesser extent, the supraclavicular block) may miss the lower trunk (ulnar nerve distribution) of the plexus. • The musculocutaneous nerve is a terminal branch of the lateral cord of the brachial plexus. It takes off from the brachial plexus sheath into the body of the coracobrachialis muscle. It needs to be blocked separately when performing the axillary nerve block. • The intercostobrachial nerve (T2) branch needs to be blocked separately if planning to cover a small area in the antero-medial aspect of the arm. It is often referred to as a tourniquet block. • Do not perform blocks on branches that are located in tight anatomical compartments (e.g., ulnar nerve blocks at the sulcus ulnaris). • The phrenic nerve proximity to the plexus explains its vulnerability to blockade during interscalene block. Blocking unilateral diaphragmatic movement can result in significant dyspnea in pulmonary cripples.

GRAPHS/FIGURES

FIGURE 1. Peripheral nerve anatomy. (Reused from www.asra.com/image-library-public.php)

See Table

FIGURE 2. Approaches to the brachial plexus block. (Reused from www.asra.com/image-library-public.php)

REFERENCES

1. Partridge BL, Katz J, Benirschke K, et al. Functional anatomy of the brachial plexus sheath: Implications for anesthesia. Anesthesiology. 1987;66:743–747. 2. Thompson GE, Rorie DK. Functional anatomy of the brachial plexus sheaths. Anesthesiology. 1983;59:117–122.

See Also (Topic, Algorithm, Electronic Media Element) • Pneumothorax • Rotator cuff repair

CLINICAL PEARLS

• History of any neurologic injury and assessment of the extent of the nerve damage should be documented before performing a brachial plexus block. • Identify the distribution of nerve supply to the area involved in the surgical procedure and apply your knowledge of anatomy of the brachial plexus when planning your regional anesthetic.

BRADYCARDIA

Piotr K. Janicki, MD, PhD Marek Postula, MD, PhD

BASICS DESCRIPTION

• Bradycardia is defined as a heart rate of <60 beats per minute (bpm). It can be secondary to: – Organic disease – Medications – Vagal tone – Healthy, well-conditioned heart • Perioperatively, treatment may consist of a temporary or permanent pacemaker for organic disease, or medications for other causes. Treatment is only indicated when the heart rate is affecting the cardiac output. EPIDEMIOLOGY Prevalence

Third-degree atrioventricular (AV) block is highest in people >70 years of age (approximately 5–10% of patients with heart disease). Prevalence

• At 20 years of age, the PR interval may exceed 0.20 seconds in 0.5–2% of healthy people. At age 60 years, >5% of healthy individuals have PR intervals exceeding 0.20 seconds. • Approximately 5% of patients with heart disease have first-degree AV block, and about 2% have second-degree AV block. Morbidity

Low heart rate observed in third-degree or Mobitz II AV block may lead to syncopal episodes with major injuries (e.g., head trauma, hip fracture), exacerbation of congestive heart failure, or exacerbation of ischemic heart disease symptoms due to low cardiac output. Mortality

The mortality of patients with sick sinus syndrome is significant and not always due to cardiac causes. ETIOLOGY/RISK FACTORS

• Intrinsic causes: – Sinus node disease – AV node disease – Idiopathic degeneration (aging)

– Infarction or ischemia (coronary artery disease and/or myocardial infarction [MI]) – Hypertension – Hypoxemia – Obstructive sleep apnea – Myxedema – Infiltrative diseases – Surgical trauma – Heart transplantation • Extrinsic causes: – Autonomically mediated syndromes – Vasovagal syncope – Pressure on the carotid sinus or carotid sinus sensitivity – Vomiting or coughing – Bezold–Jarisch reflex – Hypothermia – Increased intracranial pressure (Cushing reflex) – Electrolyte imbalance (hypokalemia, hyperkalemia) • Drugs: – Sympatholytic drugs: Beta-blockers, clonidine, neostigmine – Digoxin – Non-dihydropyridine calcium channel blockers – Antiarrhythmic agents (amiodarone, propafenone) – Lithium – Anesthetic drug overdose: succinylcholine, induction agents, neostigmine, opioids.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Sinus bradycardia is defined as a sinus rhythm with a rate <60 bpm. It is caused by an increase in vagal tone or a reduction in sympathetic tone. It is seen in: – The absence of heart disease and can occur in 25–35% of asymptomatic individuals <25 years of age as well as well-conditioned athletes and some elderly patients. – Sleep: In young and healthy patients, rates of 30 bpm and pauses of up to 2 seconds are not uncommon. • Sick sinus syndrome is chronic sinoatrial (SA) nodal dysfunction that can result from a variety of causes. It is characterized by chronic, inappropriate, and often severe bradycardia, sinus pauses, arrest, and exit block with or without appropriate atrial and junctional escape rhythms. The failure of escape pacemakers may lead to symptomatic bradycardia. Additionally, atrial tachyarrhythmias have been seen in >50% of cases. – Sinus node fibrosis: The replacement of sinus node tissue by fibrous tissue may be accompanied by degeneration and fibrosis of other parts of the conduction system including the AV node. – SA nodal artery disease: The artery may be narrowed by atherosclerosis, inflammatory processes, or emboli. – Tachycardia–bradycardia syndrome: Atrial fibrillation (AF) is the most common atrial tachyarrhythmia, and prolonged symptomatic pauses can occur after termination of AF that may result from tachycardia-mediated remodeling of the sinus node.

– Infiltrative diseases: The SA node may be affected by amyloidosis, scleroderma, hemochromatosis, and rarely tumor. – Epicardial and pericardial disease: The SA node is located near the epicardium. As a result, diseases that involve the epicardium or pericardium (such as pericarditis and tumors) may affect the SA nodal function. – Inflammatory diseases: Rheumatic fever, pericarditis, diphtheria, Chagas disease, Lyme disease, and other disorders may depress SA nodal function. – Trauma: Cardiac trauma may affect either the SA node directly or its blood supply. • AV blocks describe a delay or interruption in the transmission of an impulse from the atria to the ventricles due to an anatomic or functional impairment in the conduction system. The conduction disturbance can be transient or permanent; conduction can be delayed, intermittent, or absent. – First-degree AV block is slowed conduction without missed beats and results from a PR interval >200 ms (>210 ms at slow heart rates). – Second-degree AV block is divided into 2 types: Mobitz type I: The block is within the AV node and there is progressive PR interval prolongation, preceded by a nonconducted P wave. It is often transient and asymptomatic. Mobitz type II: The block is usually below the AV node, within the His-Purkinje system. During normal conduction, the PR interval remains unchanged prior to the P wave. However, there is paroxysmal failed conduction to the ventricles. This block is often symptomatic, with the potential to progress to complete (third-degree) AV block. – Third-degree or complete AV block may occur at the AV node, bundle of His, or bundle branches. When third-degree AV block is present, no impulses pass between the atria and ventricles. – Idiopathic progressive cardiac conduction disease (i.e., fibrosis and sclerosis of the conduction system) accounts for approximately 50% of AV blocks. – Ischemic heart disease accounts for about 40% of cases of AV block. – Cardiomyopathy and myocarditis can result from hypertrophic obstructive cardiomyopathy and infiltrative processes such as amyloidosis and sarcoidosis. Causes of myopathy include: rheumatic fever, Lyme disease, diphtheria, viruses, systemic lupus erythematosus, toxoplasmosis, bacterial endocarditis, and syphilis. – Congenital heart disease – Iatrogenic AV block Drugs: Digitalis, calcium channel blockers (especially verapamil and to a lesser extent diltiazem), amiodarone, adenosine, and beta-blockers Cardiac surgery Transcatheter closure of VSD Alcohol (ethanol) septal ablation

PREOPERATIVE ASSESSMENT • Palpate the patient’s pulse, assess EKG and pulse oximetry (strength of pulse) • Assess EKG to determine if sinus bradycardia (P wave preceded QRS complex) is present.

• Review recent events: Vagal stimulation, medications, ischemic insult, hypoxemia, hypothermia • Consider checking labs: – Electrolyte levels, magnesium, calcium – Glucose level

DIFFERENTIAL DIAGNOSIS EKG interference

TREATMENT • Bradycardia may be well tolerated if it develops slowly or is >50 bpm. Acute onset of bradycardia is more likely to be symptomatic. • Treatment should be instituted independently of the heart rate when bradycardia becomes symptomatic. In most cases the treatment threshold lies between 30 and 40 bpm. • Cease vagal stimulation – Oculocardiac reflex – Carotid sinus stimulation – Laparoscopic insufflation of the abdomen – Bladder catheterization – Electroconvulsive therapy (ECT) • Medications should be implemented when bradycardia is persistent and affecting the cardiac output. – Atropine is the drug of choice irrespective of the etiology Recommended dosing: 0.5 mg IV q 3–5 minutes to a maximum of 3 mg. Paradoxical slowing of the heart rate may be seen with doses <0.5 mg Paradoxical AV block may occur in patients s/p heart transplantation Should not delay implementation of external pacing for patients with poor perfusion Use cautiously in the presence of acute coronary ischemia or MI (increased myocardial oxygen demand) – Glycopyrrolate – Ephedrine – Dopamine, epinephrine, isoproterenol – Catecholamine infusion is an alternative for bradycardia treatment when a bradyarrhythmia is unresponsive to or inappropriate for treatment with atropine, or while awaiting pacemaker placement. • Transcutaneous (TCP) or transvenous pacing: Immediate pacing might be considered in unstable patients with high-degree AV block when IV access is not available. Additionally, if the patient does not respond to drugs or TCP, transvenous pacing is indicated.

FOLLOW-UP • Bradyarrhythmias that occur in the perioperative period are usually secondary to some other cause, such as certain medications, an electrolyte disturbance, hypoxemia, vagal

stimulation, or ischemia. • Indications for permanent pacing, regardless of associated symptoms: – Sinus bradycardia in which symptoms are clearly related to the bradycardia (usually in patients with a heart rate <40 bpm or frequent sinus pauses) – Symptomatic chronotropic incompetence – Complete (third-degree) AV block – Advanced second-degree AV block (block of ≥2 consecutive P waves) – Symptomatic Mobitz I or Mobitz II second-degree AV block – Mobitz II second-degree AV block with a widened QRS or chronic bifascicular block, regardless of symptoms – Intraventricular conduction delays, bifascicular or left bundle-branch block with or without first-degree AV block in the presence of syncope or a more advanced AV block.

REFERENCES

1. Neumar RW, Otto CW, Link MS, et al. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(Suppl 3):S729–S767.

ADDITIONAL READING

• Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for DeviceBased Therapy of Cardiac Rhythm Abnormalities: A report of the American College of Cardiology/American Heart Association Task Force on Practice. J Am Coll Cardiol. 2008;51(21):e1–e62.

CODES ICD9

• 426.0 Atrioventricular block, complete • 426.11 First degree atrioventricular block • 427.89 Other specified cardiac dysrhythmias ICD10 • I44.0 Atrioventricular block, first degree • I44.2 Atrioventricular block, complete • R00.1 Bradycardia, unspecified

See Also (Topic, Algorithm, Electronic Media Element) • Sick sinus syndrome

CLINICAL PEARLS

• Active bradyarrhythmias for which the patient should undergo evaluation and treatment before noncardiac surgery include:

– High-grade AV block – Symptomatic bradycardia – Third-degree AV heart block – Mobitz II AV block • High-grade cardiac conduction abnormalities, such as complete AV block, if unanticipated, can increase operative risk and may necessitate temporary or permanent transvenous pacing. • Intraventricular conduction delays, in the presence of a left or right bundle-branch block, but lacking a history of advanced heart block or symptoms, rarely progress to complete heart block in the perioperative period. • Atropine is a drug of choice irrespective of the type of etiology of the bradycardia; ephedrine and glycopyrrolate are also commonly used. • Unstable patients require temporary or permanent pacing. • Severe bradycardia can complicate regional anesthesia (in particular, subarachnoid or epidural anesthesia, not necessarily with high block). Ensure volume loading, vasopressors (early epinephrine), airway support, and left uterine displacement (parturients).

BRAIN DEATH

Stephanie Gargani, MD Stephen P. Winikoff, MD

BASICS DESCRIPTION

Brain death is defined as the irreversible cessation and complete absence of critical functions of the whole brain, including the brain stem. EPIDEMIOLOGY

The Organ Procurement and Transplantation Network identified the following causes of death for donors from January 1, 1988 to November 30, 2010: • All causes: 138,321 • Anoxia: 16,578 • CVA/stroke: 45,892 • Head trauma: 44,538 • CNS tumor: 883 • Other: 2,618 • Not reported: 119 • Not collected prior to 4/1/94: 27,693

ETIOLOGY/RISK FACTORS

Can be classified as either primary or secondary (see below) PHYSIOLOGY/PATHOPHYSIOLOGY

• The pathogenesis of brain death consists of primary and secondary causes: – Primary or direct causes destroy neurons. They include severe head injury, expanding intracranial mass lesions, hemorrhagic or ischemic stroke, and anoxia/asphyxia. – Secondary or indirect causes add volume to an already enclosed space and further increase intracranial pressure (ICP). As the pressure increases, it exceeds the mean arterial blood pressure and intracranial circulation will cease. This further impairs perfusion and compounds ischemia, neuronal injury, and brain death. – Several days later, intracranial pressure falls, and this allows for blood flow through the necrotic brain. Due to the ability to more rapidly diagnose brain death, evidence of frank necrosis is less often seen (1). PREVENTATIVE MEASURES

Prevention of the underlying cause of brain injury is the main goal. If injury has occurred, preventing further increases in ischemia, intracranial pressure, edema, and or bleeding is critical.

DIAGNOSIS • The American Academy of Neurology’s criteria for clinical diagnosis of brain death (2) includes prerequisites, 3 cardinal findings, and an apnea test. • Prerequisites: – Clinical or neuroimaging evidence of an acute CNS catastrophe that is compatible with the clinical diagnosis of brain death – Exclusion of complicating medical conditions that may confound clinical assessment (no severe electrolyte, acid–base, or endocrine disturbance) – No drug intoxication or poisoning – Core temperature ≥32°C (90°F) • The 3 cardinal findings in brain death: – Coma or unresponsiveness: No cerebral motor response to pain in all extremities – Absence of brainstem reflexes: Pupils will have no response to bright light; the size ranges from midposition (4 mm) to dilated (9 mm). Ocular movement: No oculocephalic reflex (testing should be avoided in patients with cervical spine fracture or instability) and no deviation of the eyes to irrigation in each ear with 50 mL of cold water (allow 1 minute after injection and at least 5 minutes between testing on each side) Facial sensation and facial motor response: No corneal reflex to touch with a throat swab, no jaw reflex, no grimacing to deep pressure on nail bed, supraorbital ridge, or temporomandibular joint Pharyngeal and tracheal reflexes: No response after stimulation of the posterior pharynx with tongue blade, and no cough response to bronchial suctioning • Apnea test: – Required prior to testing: Core temperature ≥36.5°C or 97°F Systolic blood pressure ≥90 mm Hg Euvolemia (option—positive fluid balance in the previous 6 hours) Normal PaCO2 Normal PaO2 (option—preoxygenation to obtain an arterial PaO2 of 200 mm Hg)

– Connect a pulse oximeter and disconnect the ventilator. – Deliver 100% FIO2 at 6 L/min, into the trachea (option—place a cannula at the level of

the carina). – Look closely for respiratory movements (abdominal or chest excursions with adequate tidal volumes). – Measure arterial PaO2, PaCO2, and pH after approximately 8 minutes and reconnect the ventilator. – If respiratory movements are absent and the arterial PaCO2 is 60 mm Hg, the apnea test result is positive; it supports the diagnosis of brain death. An alternate measure is a 20 mm Hg increase in the PaCO2 over a baseline normal PaCO2.

– If respiratory movements are observed, the apnea test result is negative, and the test

should be repeated. – Reconnect the ventilator if, during testing, the systolic blood pressure drops to 90 mm Hg, the pulse oximeter indicates significant oxygen desaturation, and/or cardiac arrhythmias are present. An arterial blood sample should be immediately drawn and analyzed. The test is positive if the PaCO2 is 60 mm Hg or the PaCO2 increase is 20 mm Hg over baseline normal PaCO2. The test is negative if the PaCO2 is <60 mm Hg or the PaCO2 increase is

<20 mm Hg over baseline normal PCO2; an additional confirmatory test can be

considered. • Confirmatory tests (optional in adults, but recommended in individuals <1 year of age) (2). – Conventional angiography – Electroencephalography – Transcranial Doppler – Ultrasonography – Technetium-99m scan – Somatosensory-evoked potentials

DIFFERENTIAL DIAGNOSIS

• A differential diagnosis, or more so a misdiagnosis, can be possible with other syndromes that mimic brain death (no evidence of clinical brain function). When making a diagnosis, one must rule out: – Drug intoxication – Hypothermia – Guillain–Barré syndrome – Neuromuscular blockade – Locked-in syndrome

TREATMENT • There is no treatment for brain death; it is the irreversible loss of brain function. • The correct diagnosis of brain death is critically important to ensure that: – Unnecessary treatments and procedures are not performed. – Families can have closure and are provided the chance to grieve. – Critical resources are preserved, and organ donation can be planned if those are the patient’s and family’s wishes (3).

FOLLOW-UP There are no published reports of recovery from neurologic function after a diagnosis of brain death using the criteria reviewed in the 1995 American Academy of Neurology practice parameters (4).

REFERENCES

1. Nathan S, Greer D. Brain death. Semin Anesth Perioper Med Pain. 2006;225–231.

2. American Academy of Neurology. Practice parameters for determining brain death in adults. Neurology. 1995;45:1012–1014. 3. Wijdicks EF, Varelas PN, Gronseth GS, et al. Determining brain death in adults. Neurology. 2010;74:1911–1918.

ADDITIONAL READING

• The American Academy of Neurology (AAN). www.aan.com • The Organ Procurement and Transplantation Network. http://optn.transplant.hrsa.gov/

CODES ICD9

348.82 Brain death ICD10 G93.82 Brain death

CLINICAL PEARLS

• The determination of brain death is that of a clinical diagnosis. • Pitfalls in brain death that can interfere with the diagnosis and hence require confirmatory tests: Severe facial trauma, pre-existing papillary abnormalities, toxic levels of drugs, sleep apnea, or severe pulmonary disease with retention of CO2.

• When determining brain death, the cause of the neurologic state must be known to be irreversible (4). • The majority of organ transplant donors have a diagnosis of brain death. It is possible, with mechanical ventilation, to perfuse and maintain function of vital organs, despite the lack of brain activity and legal death. This provides time for harvesting of organs.

BREATHING CIRCUIT

Verghese T. Cherian, MBBS, MD, FFARCSI

BASICS DESCRIPTION

• The breathing circuit connects components of the anesthesia machine to the patient’s airway. It maintains a bidirectional flow between the patient’s lungs and the ventilator/reservoir bag, delivering oxygen and anesthetic agent while carrying exhaled gas away from the patient. • The circle system is essentially composed of: – Fresh gas inlet – 2 unidirectional valves – Breathing tubes with a Y-piece – Reservoir bag – Canister containing CO2 absorbent

– Adjustable pressure limiting (APL) valve • It also contains additional components: – Pressure gauge – Oxygen analyzer – Positive end-expiratory pressure (PEEP) valve – Bacterial filter • Advantages of a circle system include: – Relative stability of inspired gas concentration – Conservation of respiratory moisture and heat (co-axial circuits further improve this) – Reduction of waste in volatile anesthetics (financial savings and decreased environmental pollution)

PHYSIOLOGY PRINCIPLES

• Circuits are described as open, semi-open, closed, and semi-closed: – Open circuit systems describe “non-circle” circuits such as the “open drop” technique. Historically, cloths saturated with volatile anesthetic were applied over a patient’s face and mouth. This technique provided little control over volatile agent delivery and is not used today in developed countries. – Semi-open systems describe “non-circle” circuits such as the Mapleson A, B, C, D, and E circuits. These systems lack a scavenging system and the ability to absorb CO2; hence they require high fresh gas flows (FGF) to prevent rebreathing of CO2. Additionally, they

cannot humidify and warm inspired gases (except the Mapleson D/Bain circuit) (1). – Closed circuit systems are also “circle” circuits, but the FGF and volatile agent delivered are titrated to match the patient’s consumption or uptake, respectively. CO2 is absorbed by a CO2 absorbent; however, “extra” fresh gas flows are not scavenged.

– Semi-closed systems are “circle” circuits, have additional components, are today’s modern circuits on anesthesia machines, and are the focus of the current chapter. • Fresh gas inlet is positioned between the canister and inspiratory unidirectional valve. • Unidirectional valves are lightweight discs on an annular seat which ensure movement of gases in one direction. • Breathing tubes are attached to the inspiratory and expiratory ports on the canister and at the patient-end to the Y-piece. They carry gases to and from the patient. A single-limb circle system is available wherein the inspiratory and the expiratory channels are side-by-side, within one tube, separated by a partition. • Reservoir bag is located diagonally across from the patient with the unidirectional valves on either side. It provides: – Peak inspiratory flows of ∼60 L/min, which exceeds the FGF – A means for manual ventilation – A “reservoir” of volatile agent; at the time of emergence, compressing and emptying the bag aids with removal of volatile agent that can otherwise slow awakening (“rebreathing” of agent). • Canister containing CO2 absorbent is attached to the anesthesia machine and houses the APL valve, fresh gas inlet, and the unidirectional valves. It is transparent to allow detection in a change in the color of the absorbent. CO2 absorbents are available in 3 formulations:

– Soda lime: Ca(OH)2 80%, NaOH 4%, KOH 1%, silica, and kieselguhr. It has an absorbent capacity of 26 L of CO2/100 g.

– Baralyme (discontinued in 2004 due to potential for extreme heat and fires): Ba(OH)2 20%, Ca(OH)2 80%

– Calcium hydroxide lime: Ca(OH)2, CaCl, CaSO4, polyvinylpyrrolidone. It has an absorbent capacity of 10.2 L of CO2/100 g.

– Indicators are added to signal the exhaustion of the absorptive capacity of the absorbent, by changing color based on the pH. Ethyl violet is a commonly used indicator which changes from white to violet. • APL valve is located between the expiratory unidirectional valve and the canister. Opening pressure is 1 cm H2O at the “open” position and 60–70 cm H2O at the “closed” position. During mechanical ventilation, the APL valve is isolated from the circuit. • 3 essential rules are implemented in any circle system to ensure that the exhaled gases pass through the canister for CO2 absorbent, before they are rebreathed:

– Unidirectional valves must be located between the patient and the reservoir bag, one on the inspiratory and the other on the expiratory limb of the circuit. – The fresh gas inflow should not enter the circuit between the patient and the expiratory unidirectional valve. – The APL valve cannot be located between the inspiratory unidirectional valve and the patient. • The positions of the other components are arranged to achieve the optimal compromise of conservation of fresh gas, humidification and warming of inspired gases, economical use of soda lime, and practicality.

ANATOMY

Components are arranged in a circular manner (as shown in Figure 1). DISEASE/PATHOPHYSIOLOGY

• Disadvantages of the circle system include: – Complex design – Multiple connections that open up the potential for misconnections, disconnections, and leaks – Malfunction of unidirectional valves: The open position results in rebreathing, while the closed position can cause high airway pressure. • In a single-limb circuit, disruption in the partition between the inspiratory and expiratory channels will increase the dead space as well as the interaction between anesthetics and absorbents. • Compound A from sevoflurane usage: – Sevoflurane may degrade to form a toxic substance named Compound A (fluoromethyl2,2-difluoro-1-trifluoromethyl vinyl ether) when it comes in contact with soda lime. – This is enhanced with low FGF, increased sevoflurane concentrations, higher absorbent temperatures, and fresh absorbent. – In animal studies, Compound A has been shown to cause renal necrosis. However, histologic evidence and case reports have not demonstrated this in humans. Nonetheless, to avoid this potential, a minimum of 2 L/min FGF is often utilized. • Carbon monoxide (CO) formation can result from prolonged contact between absorbent and anesthetic. – The amount increases with the use of desiccated absorbent, use of baralyme compared to soda lime, higher temperature of the absorbent, higher anesthetic concentrations, and low FGF rates. – Increased production is also dependent on the type of volatile anesthetic, with desflurane ≥ enflurane > isoflurane > halothane = sevoflurane. • Fire within the canister can result when sevoflurane is administered with desiccated baralyme, higher temperature of the absorbent, higher anesthetic concentration, and low FGF rates. Indicators of a decomposition reaction between sevoflurane and absorbent include a rapid change in color of the absorbent or a slow rise in inhaled sevoflurane concentration compared to the vaporizer concentration control dial setting. PERIOPERATIVE RELEVANCE

• Oxygen – The oxygen consumption for most patients is 200–250 mL/min; FGF should be adequate to replace this (in a closed circuit system, the FGF needs to match this). – Pre-oxygenation is achieved in 3 minutes with an oxygen flow of 5 L/min. • Fresh gas flow – High flow >1,000 mL/min – Low flow <1,000 mL/min – Minimal flow <500 mL/min – Metabolic flow = 250 mL/min

– FGF replaces the gases that are taken up by the patient and that which are vented out of the circuit. – In a “closed” circle system, the FGF replaces the oxygen and the anesthetics taken up by the tissues. Initially, the tissue uptake of nitrous oxide and volatile anesthetic gases is high but decreases with time while the uptake of oxygen is maintained. This can be partially overcome by providing a higher FGF (3 L/min) for the initial 15 minutes, which corresponds to the period of peak tissue uptake, before initiating “minimal” flow of oxygen. • Carbon dioxide – In clinical settings, the arterial CO2 is dependent on the minute ventilation rather than the FGF, unlike in the Mapleson circuit. – In a circle system, rebreathing is possible if the absorbent is exhausted or if the unidirectional valve is stuck in the open position. This will appear as “high” inspired CO2 on the ETCO2 monitor.

Pediatric Considerations

• The dead space extends from the patient port of the Y-piece to the partition between the breathing tubes. • Thus, any gadget (filter, ETCO2 adapter) between the Y-piece and the patient would increase

the dead space, unacceptably, in a small child. • Calculation of actual minute ventilation may be difficult due to the compression of the gases within the distensible corrugated tubes. Therefore, in pediatric patients, short, thinner tubes are used with a standard canister. • Checking the integrity of the circle system: – The “leak” test involves closing the APL valve and Y-piece while using the oxygen flush to pressurize the system to at least 30 cm H2O. If the pressure in the system is maintained for 10 seconds, it can be considered leak-free. – The “flow” test involves attaching the reservoir bag to the Y-piece and ventilating using the mechanical ventilator. Cyclical inflation and deflation of the bag ensures a patent circuit with functioning unidirectional valves. • The integrity of the circle system is checked during the “self-test” which is incorporated into newer anesthesia workstations. • The in-line pressure gauge monitors the pressure in the circuit, and the in-line oxygen analyzer measures the percentage of oxygen delivered.

GRAPHS/FIGURES CIRCLESYSTEM

REFERENCES

1. Taha S, El-Khatib M, Siddik-Sayyid S, et al. Preoxygenation with the Mapleson D system requires higher oxygen flows than Mapleson A or circle systems. Can J Anaesth. 2007;54(2):141–145. 2. Feldman JM. Managing fresh gas flow to reduce environmental contamination. Anesth Analg. 2012 March 13.

ADDITIONAL READING

• Dorsch JA, Dorsch SE, eds. The circle system. In: Understanding anesthesia equipment, 5th ed. Philadelphia: Wolters Kluwer, 2008:223.

See Also (Topic, Algorithm, Electronic Media Element) • Alveoli • Alveolar • Dead space • CO2 transport

• Oxygen analyzers on the anesthesia machine

CLINICAL PEARLS

• There are 3 essential rules to ensure that the exhaled gases pass through the canister for the CO2 absorbent before they are rebreathed:

– A unidirectional valve must be located between the patient and the reservoir bag, one on the inspiratory and the other on the expiratory limb of the circuit. – The fresh gas inflow should not enter the circuit between the patient and the expiratory unidirectional valve. – The APL valve cannot be located between the inspiratory unidirectional valve and the patient.

• In clinical settings, the arterial CO2 is dependent on the minute ventilation rather than the FGF, unlike in the Mapleson circuits. • The use of low FGF and closed circuits can decrease the ecotoxicologic effects (ozone depletion, global warming) of volatile agents and nitrous oxide (2).

BRONCHIECTASIS

Gregory E. R. Weller, MD, PhD

BASICS DESCRIPTION

• The term “bronchiectasis” stems from the Greek words bronchus (windpipe) and ektasis (stretching). • It is a disease state of abnormal and irreversible dilation of bronchial tree branches which results from congenital airway syndromes (e.g., cystic fibrosis) or acquired causes (recurrent bronchial infections). • Bronchiectasis is characterized by a chronic neutrophilic inflammation and secretory response, with excessive and tenacious mucous production leading to an obstructive defect. • Exacerbations can lead to respiratory failure.

EPIDEMIOLOGY Incidence

• 1–10 per 100,000 people • In the pre-antibiotic era, onset was usually in childhood; in modern times, it is more commonly diagnosed in adults. Prevalence

• In the US: 100,000–200,000 persons • It has decreased in modern times with the use of antibiotics, but diagnosis is again increasing with more frequent use of high-resolution CT imaging (allows for improved detection). • Slightly Female > Male.

Morbidity

• Severity and frequency of symptoms is highly variable. • One large study showed an average of 1.5 exacerbations per year per patient.

Mortality

• In the US: Approximately 1,000 per year • Mortality rate is similar to that for asthma or chronic obstructive pulmonary disease (COPD). ETIOLOGY/RISK FACTORS

• Postinfectious (recurrent or persistent respiratory infections): – Bacterial – Viral – Fungal

• Bronchial obstruction • Congenital diseases: – Cystic fibrosis (CF) (most common) – Kartagener’s syndrome (also known as primary ciliary dyskinesia) can present as bronchiectasis, situs inversus, and chronic sinusitus. – Other mucociliary defects – Alpha-1-antitrypsin deficiency – Immunodeficiency states • Chronic aspiration or gastroesophageal reflux • Idiopathic • May be a feature of: – COPD – Asthma – Sarcoidosis and other autoimmune diseases – Bronchiolitis obliterans

PATHOPHYSIOLOGY

• Although there are numerous etiologies, the common pathway is chronic bronchial inflammation and recurrent cycles of airway infection. • Persistent inflammatory infiltration of muscle layers and supportive airway cartilage leads to the replacement of elastic tissue with fibrous tissue, causing irreversible dilation of bronchial branches. Can be localized or diffuse. • Chronic inflammation leads to: – Mucous gland hypertrophy – Lymphoid hyperplasia – Impaired ciliary function – Copious purulent secretions – Increased vascularity of pulmonary mucosa, with extensive collateral blood flow • Pulmonary function testing reveals: – Obstructive airflow defects (due to secretions and lymphadenopathy): Decreased FEV1,

FEV1/FVC, increased residual volume. Progressive pulmonary decline shows an average FEV1 decrease of 1–3% per year (~50 mL/year in adults).

– Restrictive defects can be seen in advanced cases. • Generally results in poor pulmonary reserve

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess severity of disease and current exacerbations • Optimize pulmonary function • Assume poor pulmonary reserve – Anticipate intraoperative airway secretions, obstruction, possibility of hemoptysis or pneumothorax, and progressive respiratory compromise – Anticipate possible postoperative pulmonary complications

PREOPERATIVE ASSESSMENT

SYMPTOMS

• Chronic productive “wet” cough • Dyspnea on exertion • Constitutional symptoms: – Fatigue – Weight loss • Hemoptysis

History

• Age of onset • Underlying etiology • Frequency of cough • Daily sputum production • Frequency of exacerbations • Hospitalizations • Hemoptysis

Signs/Physical Exam

• Wet cough • Sputum production • Respiratory noises (wheezes, rales) • Cyanosis • Clubbing of the digits, if extreme

TREATMENT HISTORY

• Individualized for etiology and course; elucidate treatment history for both chronic course and exacerbations. • Pulmonary hygiene to expel mucous and open up airways: – Chest PT – Postural drainage – Cough assistance • Surgical options: – Bronchoalveolar lavage – Resection for failed medical therapy or for uncontrolled hemoptysis • Lung transplantation

MEDICATIONS

• Antimicrobials, guided by sputum microbiology (1)[A] • Anti-inflammatory – Inhaled corticosteroids (2)[B] – Oral corticosteroids – Oral macrolides – Inhaled NSAIDs • Bronchodilators: – Beta-agonists

– Anticholinergics – Theophylline – Leukotriene antagonists • Inhaled mucolytics

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• High-resolution chest CT (gold standard) shows bronchial dilatation, bronchial wall thickening, “tram lines” or “signet ring” formations. • CXR may show bronchial dilatation, atelectasis, bronchial wall thickening, hyperinflation, and cysts. • Flexible fiberoptic bronchoscopy • Pulmonary function testing • Consider ABG (PaO2 and PaCO2) • Sputum culture • WBC count (look for current infection) • Temperature (look for current infection) • Immunoglobulin levels (look for immunodeficiencies) • Consider echocardiographic assessment of right heart function

CONCOMITANT ORGAN DYSFUNCTION

Chronic hypoxemia may lead to pulmonary vasoconstriction, pulmonary hypertension, and right heart dysfunction, e.g., cor pulmonale. CIRCUMSTANCES TO DELAY/CONDITIONS

Postpone elective surgery if acute exacerbation, e.g., active infection, hemoptysis, worsening productive cough. CLASSIFICATIONS

Commonly associated with cystic fibrosis, so often designated as “CF” or “non-CF” bronchiectasis

TREATMENT PREOPERATIVE PREPARATION Premedications

• Consider avoiding sedatives if moderate-to-severe disease, due to poor pulmonary reserve • Consider bronchodilators • Stress dose steroids if recent steroid therapy

INTRAOPERATIVE CARE Choice of Anesthesia

• Regional anesthesia as a sole technique, if appropriate, has the benefit of avoiding airway

instrumentation and the need for positive pressure ventilation. • Regional anesthesia in combination with general anesthesia can decrease the need for systemic opioids. Neuraxial techniques can improve postoperative deep breathing and pulmonary mechanics. • Goal is to maintain optimal pulmonary function in the setting of chronically poor pulmonary reserve.

Monitors

• Consider arterial line for ABGs • Vigilance for capnograph changes; sloping in the plateau portion of the waveform suggests obstruction.

Induction/Airway Management

• Caution with nasal intubations due to the possibility of chronic sinusitis • Achieve deep anesthesia prior to airway instrumentation or surgical stimulation to minimize coughing and airway reactivity. – Although ketamine is a potent intravenous bronchodilator, it can increase secretions and is undesirable. – Consider mask ventilating with volatile agents to achieve bronchodilation prior to airway instrumentation. – Ensure adequate dosing and onset time for neuromuscular blockade. • For pulmonary surgery, lung isolation is needed to minimize the transfer of infected secretions from bronchiectatic regions to healthy lung tissue.

Maintenance

• Careful, frequent suctioning due to increased quantity and tenacity of airway secretions • Humidify inhaled gases to soften secretions • Vigilance for bronchospasm/obstruction; the capnograph tracing should be closely monitored. Treat bronchospasm by: – Deepening the anesthetic with increased volatile agent (potent bronchodilators) – Deepening the anesthetic with intravenous agents (e.g., propofol) – Administering inhaled beta-agonists • Be vigilant for the possibility of hemoptysis due to increased vascularity of bronchiectatic lung tissue, pneumothorax, and spillage of suppurative secretions from bronchiectatic areas to healthy pulmonary tissues.

Extubation/Emergence

• Usual extubation criteria, with vigilance for secretions and awareness of elevated risk for postoperative respiratory distress. • Antimuscarinics may thicken secretions; consider reducing the dose if appropriate.

POSTOPERATIVE CARE BED ACUITY

• Disposition depends on the patient’s preoperative condition, surgical procedure,

intraoperative course, and airway condition. • Frequent careful suctioning • Incentive spirometry • Supplemental oxygen • Monitor for respiratory distress

MEDICATIONS/LAB STUDIES/CONSULTS

• Consider ABG for PaO2 and PaCO2, as appropriate • Chest radiography • Echocardiogram, if concern for right heart failure

COMPLICATIONS

• Fever (e.g., pneumonitis from suppurative secretion, spillage into previously healthy lung tissue, or bacteremia from airway manipulation) • Respiratory distress/failure: – Hypoxemia – Hypercarbia – Respiratory acidosis – Retained secretions

REFERENCES

1. Evans DJ, Bara A, Greenstone M. Prolonged antibiotics for purulent bronchiectasis in children and adults. Cochrane Database Syst Rev. 2007;2:CD001392. 2. apur N, Bell S, Kolbe J, et al. Inhaled steroids for bronchiectasis. Cochrane Database Syst Rev. 2009;1:CD000996. 3. O’Donnell AE. Bronchiectasis. Chest. 2008;134:815–823. 4. Redding GJ. Bronchiectasis in children. Pediatr Clin N Am. 2009;56:157–171. See Also (Topic, Algorithm, Electronic Media Element) • Asthma • Chronic obstructive pulmonary disease • Cor pulmonale • Cystic fibrosis • Pulmonary function tests • Postoperative pulmonary complications

CODES ICD9 • 494.0 Bronchiectasis without acute exacerbation • 494.1 Bronchiectasis with acute exacerbation • 748.61 Congenital bronchiectasis

ICD10

• J47.1 Bronchiectasis with (acute) exacerbation • J47.9 Bronchiectasis, uncomplicated • Q33.4 Congenital bronchiectasis

CLINICAL PEARLS

• Clinical presentation is variable; a high-resolution CT is the gold standard for diagnosis. • Diverse underlying etiologies mean there is no universal treatment. Additionally, there is sparse, high-quality, randomized controlled trial data available regarding the efficacy of particular treatment strategies for bronchiectasis, especially in children. • Avoid elective surgery during exacerbations • Airway secretions of increased volume and tenacity can complicate the entire perioperative course. • Similar to asthma and COPD, bronchiectasis increases the postoperative risk for respiratory compromise.

BRONCHOSCOPY, FLEXIBLE AND RIGID Joshua A. Atkins, MD, PhD

BASICS DESCRIPTION General

• In the operating room (OR), bronchoscopies are typically performed by interventional pulmonologists or thoracic surgeons (and by intensivists in the ICU) for a myriad of indications: – Visual inspection of the airway to assess for dynamic airflow obstruction, tumor, source of bleeding, glottic dysfunction or edema, or bronchial disruption (3) – Biopsy for diagnosis of intrabronchial or peribronchial lesions (via endobronchial ultrasound) – Injection of collagen for vocal cord paralysis – Placement or revision of a stent for airway mass or collapse – Ablation of airway lesion – Retrieval of foreign body – Assessment of airway bleeding – Emergent airway stenting in acute obstruction (e.g., mediastinal mass) – As a component of pan-endoscopy surveillance for surgical evaluation of head and neck cancer for esophagoscopy with dilation of stricture – Laser ablation of airway papilloma • An increasingly wide range of procedures can be performed via flexible bronchoscopy. Rigid bronchoscopy is more invasive and tends to be reserved for more aggressive interventional procedures such as stent placement. Incision None

Approximate Time

15 minutes to 2 hours EBL Expected

Minimal except in bleeding mass, hemoptysis, or resection Hospital Stay

Typically outpatient unless coexisting disease or primary illness necessitates otherwise Special Equipment for Surgery

• Laser in some procedures • Endobronchial ultrasound equipment

• Pathology/cytology availability • High-frequency jet ventilator • Airway catheters and tube exchangers such as Aintree intubation catheter • Small and large bore endotracheal tubes (4, 5, 6, 9 mm and MLT) depending on surgeon preference • Nebulizer

EPIDEMIOLOGY Prevalence

Majority of procedures are in patients with lung disease, especially lung cancer. Morbidity

• Sore throat • Bleeding or hematoma • Airway swelling • Severe coughing • Obstruction • Aspiration • Tracheal/bronchial disruption from mucosal tear

Mortality Rare

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Broad range of anesthetic options. Anesthetic plan should be formulated only after direct consultation with the surgical team as to type of procedure planned, patient comorbidities, and risk level for maintaining airway patency. • Challenging airways with limited pulmonary reserve should be assumed. • Multiple different airway devices and modalities may be used in a single procedure. Be prepared for alternative strategies.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Dysphagia • Hoarseness • Dyspnea and positional effects • Hemoptysis • GERD • Asthma • Cough

History

Underlying disease and prior treatment

Signs/Physical Exam

• Airway exam with history of obstruction • Clubbing • Pulse oximetry <92% on room air • Tachypnea or stridor • Weak cough • Inability to lie flat • Fever (concomitant pneumonia)

MEDICATIONS

• Home oxygen • Antibiotics for active pneumonia • Inhalers (beta-agonists, steroids, anticholinergics) • Systemic steroids • Surgeon may desire discontinuation of NSAIDs depending on risk factors.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC (hemoglobin and white blood count) • Chemistry panel (assess [HCO3-])

• Flow-volume loops if concern for dynamic obstruction • Chest radiograph (active infection, pleural or pericardial effusion, pulmonary edema) • CT scan may be available and can aid with assessing anatomy of lesions or potential difficulties with ventilation or securing the airway. CONCOMITANT ORGAN DYSFUNCTION

• If the underlying pathology is associated with COPD or intrinsic lung disease, the patient may demonstrate pulmonary hypertension and cardiac dysfunction from chronic hypoxemia. • Decreased pulmonary volumes and capacities secondary to prior lung surgery or intrinsic lung disease

TREATMENT PREOPERATIVE PREPARATION Premedications

• Consider midazolam (caution in chronic hypoxemia or airway lesion prior to OR) • Consider glycopyrrolate to diminish secretions (caution for tachycardia) • Consider nebulized lidocaine (8 mL of 2% solution over 15–20 minutes) in the holding area

Special Concerns for Informed Consent

• Patients with significant disease, poor functional status, or extensive procedure may require postoperative intubation and should be counseled.

• If starting the case with sedation, patients should be counseled that amnesia may be incomplete.

INTRAOPERATIVE CARE Choice of Anesthesia

• Flexible bronchoscopy: It is common to start with topicalization with or without sedation for the initial assessment and progress to general anesthesia, as necessary. The maintenance of spontaneous ventilation is often advantageous during functional assessment and may be crucial in patients with severe obstruction. • Rigid bronchoscopy invariably requires general anesthesia. Muscle relaxation is not essential, but immobility is imperative to avoid traumatic injury to teeth, glottis, or tracheobronchial tree.

Monitors

• Standard ASA monitors • Consider invasive arterial monitoring for serial ABGs in patients with poor baseline function undergoing long procedures. • Processed EEG for high-risk patients (rapid swings in stimulus level) should be considered. The avoidance of muscle relaxants may further facilitate identification of inadequate depth of anesthesia. • During sedation, continuous capnometry should be monitored.

Induction/Airway Management

• Strongly consider pre-induction topicalization with nebulized lidocaine and/or targeted nerve blocks for both awake and asleep procedures. The total dose of lidocaine should be monitored (doses may need to be decreased in patients with liver disease). The patient should be monitored for local anesthetic systemic toxicity. • Most procedures are performed with the bed rotated to 90° away from the anaesthetist; starting in this position will facilitate immediate intervention by the proceduralist. • For sedation, agent selection should focus on the goals for the individual patient. Many approaches will produce suitable results, and the key is to achieve a smooth equilibrium to avoid bolusing at unfavorable points during the procedure. – Remifentanil infusion can be considered (0.25–0.5 mcg/kg bolus followed by 0.05 mcg/kg/min) and titrated in increments of 0.02 mcg/kg/min every 3–5 minutes to attain the desired effect (1)[A]. The key is slow titration to allow CO2 levels to build as the

apneic threshold is raised, provide immobility, and blunt the cough reflex. Chest wall rigidity or glottic spasm is possible with high doses. The addition of benzodiazepines to this infusion will have unpredictable effects and may exaggerate sedation levels. – Dexmedetomidine infusion is very effective for the maintenance of respiratory drive and following commands (1)[A]. Consider a slow loading dose of 0.5–1.0 mcg/kg over 10 minutes prior to a maintenance dose of 0.3–1.0 mcg/kg/h. Upper airway obstruction can still be observed, but the patient should remain responsive. Amnesia is unreliable. – Ketamine (0.5 mg/kg bolus; 3–10 mcg/kg/min) can be combined with dexmedetomidine for added hypnosis and analgesia with limited respiratory effects for stimulating

procedures (1)[A]. Consider co-administration of an antisialagogue to decrease secretions. • General anesthesia is typically induced via intravenous medications, unless the goal is to maintain spontaneous ventilation for any part of the procedure (e.g., foreign body removal, tracheal stenosis, tracheomalacia, anterior mediastinal mass). • Airway – Flexible bronchoscopy: The airway can be readily secured with a disposable, classic LMA. A bronchoscope adapter should be available to facilitate simultaneous ventilation and bronchoscopy; supportive struts, if present, should be cut away. Alternatively, a small, uncuffed (or deflated) endotracheal tube may be placed. – Rigid bronchoscopy: A small, uncuffed (or deflated) endotracheal tube may be placed and the rigid scope inserted alongside it. Alternatively, air entrainment or jet ventilation via the side-port of the rigid bronchoscope may be utilized. Jet ventilation will deliver more reliable ventilation than standard positive pressure ventilation via an endotracheal tube in a partially open circuit. Automated jet ventilators with pressure alarms should be strongly considered to limit the risk of barotrauma (2).

Maintenance

• The procedure necessitates frequent disconnection from the ventilation circuit, repositioning of airway devices, and introduction of airway instruments. If inhaled anesthesia is used, delivery will be variable and significant room contamination is unavoidable. To that extent, intravenous maintenance is strongly preferred unless spontaneous ventilation is desired. • Avoid long-acting opioids as post-procedure respiratory compromise is to be expected. • Local anesthetic in the airway will provide adequate pain relief in most cases. • Consider dexamethasone for dual-agent postoperative nausea/vomiting prophylaxis and modulation of edema. • Consider placing a processed EEG if total intravenous maintenance is used with muscle relaxation.

Extubation/Emergence

• After a general anesthetic, the goal is to confirm adequate recovery of respiratory function prior to extubation of LMA removal. • Suctioning of the airway should be done before extubation to remove any accumulated blood. • In patients who are significantly compromised at baseline or following an extensive procedure, postoperative intubation should be strongly considered. Communicate with the surgeon to confirm clinical impressions and the extent of procedure.

POSTOPERATIVE CARE BED ACUITY

• Continuous pulse oximeter monitoring for patients on chronic oxygen

ANALGESIA

• Acetaminophen • Short-acting opioids if needed

COMPLICATIONS

• Respiratory failure with hypercarbia, hypoxemia, aspiration • Bleeding in the airway • Tracheal or bronchial tear with mediastinal emphysema or crepitus • Glottic trauma or edema; particularly from rigid scope • Dislodged airway stent • Dental injury

REFERENCES

1. Atkins JH, Mirza N. Anesthestic considerations and surgical caveats for upper airway surgery. Anesthesiol Clin. 2010;28(3):555–575.

2. Hautmann H, Gamarra F, Henke M, et al. High frequency jet ventilation in interventional fiberoptic bronchoscopy. Anesth Analg. 2000;90(6):1436–1440. 3. Conacher ID. Anaesthesia and tracheobronchial stenting for central airway obstruction in adults. Br J Anaesth. 2003;90(3):367–374.

ADDITIONAL READING

• Pawlowski J, Pratt SD. Anesthesia for bronchoscopy. In: Ernst A, ed. Introduction to bronchoscopy. New York, NY: Cambridge University Press, 2009.

See Also (Topic, Algorithm, Electronic Media Element) • Jet ventilation

CLINICAL PEARLS

• Bronchoscopies are performed for such a wide range of indications and conditions that a clear appreciation of the goals and needs of the proceduralist must be achieved prior to the start of anesthesia care. • There is no substitute for adequate topical anesthesia of the airway when bronchoscopy is performed under sedation or general anesthesia with spontaneous ventilation. • Be prepared for departure from the original anesthetic plan as the scope of the procedure commonly changes as a result of the initial diagnostic assessment (e.g., flexible bronchoscopy followed by a rigid bronchoscopy with dilation and stenting).

BUFFERING SYSTEMS Horst Rieke, MD, PhD Carlee Clark, MD

BASICS DESCRIPTION

• Biochemical and metabolic functions occur most optimally within a narrow pH range (7.35– 7.45). Acidosis and alkalosis, therefore, have significant physiologic impact such as neurophysiologic dysfunction as well as decreased inotropy, enzyme activity, cerebral and myocardial microperfusion, and catecholamine efficacy. Additionally, the oxyhemoglobin curve shifts and electrolyte abnormalities occur. • Acid–base buffering systems within the body serve to keep the physiologic concentration of hydrogen ions (H+) constant; they serve as a reservoir or cushion. There are several systems that provide overlap and graduated lines of defense against pH disturbances. They include chemical (bicarbonate, proteins, phosphate), respiratory, renal, liver, and bone buffering systems. • Despite their large capacity, when buffering systems fail or are overwhelmed, pH and physiologic abnormalities manifest. The pH range required for compatibility with life is between 6.8 and 7.8. PHYSIOLOGY PRINCIPLES

• Acids are compounds that contain hydrogen and release H+ when dissolved in solution; they are proton producers or “donors.” The terms “strong” and “weak” refer to the donor’s “willingness” or “ability” to donate the H+. A strong acid readily dissociates its H+ from the conjugate base (A−; anion). A weak acid does not easily donate its H+ and will exist mostly in the HA form. • Bases are compounds that contain hydroxide and release hydroxide ion (OH−) when dissolved in solution; they are OH− producers, or conversely H+ acceptors. A strong base readily dissociates its OH− from the conjugate acid (C+; cation). A weak base does not easily donate its OH− and will exist mostly in its COH form. • The concentration of H+ in distilled water is very small (0.0000001 mol/L, or 10−7 mol/L). The concept of pH provides a useful way of describing these small values in a comprehensible manner; pH is a negative logarithm of the concentration of H+ (equation 1). A decrease in pH signifies an increase of H+ and vice versa. – pH = log 1/[H+] – [H+] = 0.0000001 = pH of 7 • Neutralization of acids and bases occur when they bind to a conjugate base or acid, respectively. An example of this is H+ + OH− → H2O, where the free H+ and OH− disappear and the pH does not change. This is the concept behind buffering systems.

• Buffering capacity describes the capability of a buffering system to neutralize acid or base. The capacity increases when there is an increase in the number of buffer molecules ready to bind additional H+ (or OH−). • Chemical buffering systems are the body’s first line of defense against acid–base abnormalities. They act within seconds to minutes, with the purpose of minimizing changes in pH when an acid or base is added. Buffering solutions comprise either a weak acid and its conjugate base or a weak base and its conjugate acid. – Bicarbonate (HCO3−) and carbonic acid (H2CO3) are abundant in the extracellular fluid (ECF) making this the most important buffer system in the ECF for noncarbonic acids (1). The CO2/HCO3− buffer ratio is 1:20; however, the ability for CO2 to be eliminated by ventilation changes it from a “closed” to an “open” system. Alveolar ventilation selfadjusts to keep the pCO2 constant. Additionally, the renal system is capable of adjusting the HCO3− concentration.

– Proteins are important buffers of the intracellular space because they contain both acidic and basic groups to combine with H+ or OH−. – Hemoglobin molecules buffer H+ from carbonic acids; it has a buffering capacity 5–6 times that of plasma proteins. The hemoglobin molecule can bind either O2

(oxyhemoglobin) or H+ (deoxyhemoglobin) at any given time, but not both; additionally, binding of one results in release of the other (this exchange/trade is known as the Bohr effect). This is physiologically advantageous; in the the peripheral circulation where H+ is increased from tissue metabolism, O2 is unloaded to the tissue.

– Amino groups of intracellular proteins have pK values close to the physiologic pH, rendering these substances important intracellular buffers. – Phosphate exists in several compartments: Blood/intravascular, intracellular, and urine. With a pKa of 6.9, H2PO4− readily binds to H+. Intracellularly, phosphate is present in

high concentrations, and plays an important buffering role. However, in extracellular compartments, its low concentration relegates it to a more minor role. Phosphates also contribute to H+ excretion in the renal tubules. • Respiratory system: During aerobic metabolism, the mitochondria generate ATP while producing CO2 as a byproduct. CO2 is capable of easily diffusing across lipid cell membranes into the blood stream and erythrocytes because it is not ionized or charged. Inside erythrocytes, CO2 is converted into HCO3− via carbonic anhydrase. HCO3− is unable

to diffuse out of the erythrocyte due to its ionization (cannot cross the lipid membrane); instead it is stored and transported from peripheral tissues to the lungs. When reaching the lungs, HCO3− within the erythrocyte gets reversed to CO2 and diffuses into the alveolar

space to be exhaled. – Alveolar ventilation and respiratory drive are adjusted by brainstem centers in response to changes in pH. Because alveolar ventilation is easily increased and decreased, the range of shifting the CO2 elimination up and down is large and the response is very fast. In addition, this is facilitated by the almost linear CO2-binding curve in blood.

• Renal system: Although the kidneys are slower to respond to changes in pH, they have a tremendous buffering capacity. At the glomerulus and Bowman’s capsule, HCO3− and H+ are filtrated from the blood into the renal tubule. – In the lumen: H+ can combine with titratable acids (HPO4−, SO4−, NH3) and be excreted.

H+ can bind to HCO3- via carbonic anhydrase (present in the lumen) to form H2O and CO2. The CO2 readily diffuses into the renal cells and out to the capillaries (~85% of the

filtrated bicarbonate is reabsorbed in the proximal tubules). – Aldosterone also stimulates direct H+ excretion in the collecting ducts. • Liver metabolism: Although hepatic metabolism produces HCO3−, CO2, and NH4+

byproducts, these compounds are consumed and “buffered” during urea synthesis. In the event of incomplete consumption, NH4+ is released into the circulation, where it is either

consumed during glutamine synthesis (which in turn facilitates renal tubular H+ excretion) or excreted in the urine. Additionally, the liver eliminates H+ with the cleavage of lactic acid, acetoacid, and citric acid. • Bone: Functions as a buffer via ionic exchange (acute) and dissolution of bone crystal (chronic). Bone “takes up” H+ in exchange for calcium, sodium, and potassium in acidemic states. In alkalemic states, it releases HCO3−, CO3−, or HPO4−. Ionic exchange does not

involve bone breakdown and deals with acute acidosis. Chronic intracellular acidosis in osteoclasts causes an intracellular hypocalcemia and osteoclast stimulation. The result is bone breakdown involving the release of calcium carbonate via direct physiochemical breakdown of crystal, which is independent of parathyroid hormone. • GI tract: Small bowel and pancreatic exocrine secretions reverse gastric acids but are of minor importance for the systemic buffering of the whole body.

ANATOMY

• Changes in pH are communicated between the ICF and the ECF via CO2 transfer across the

cell membrane and proton–cation exchange mechanisms. It should be noted that only the extracellular space is clinically accessible for monitoring of test parameters. • Regulatory organs for maintenance of acid–base balance include the: – Lungs exhaling and excreting CO2 by adapting the alveolar ventilation to normalize PaCO2 – Circulation matching oxygen delivery to oxygen demands – Kidneys excreting and reabsorbing acid–base relevant substances – Liver providing metabolism and synthesis of glutamine and proteins

DISEASE/PATHOPHYSIOLOGY

Acid–base imbalances result from the failure of the total of the buffering systems. Depending on the details of the underlying cause, various outcomes of failure of the buffering system can be described: • Metabolic acidosis or alkalosis • Respiratory acidosis or alkalosis

• Partial metabolically compensated respiratory acidosis or alkalosis • Partial respiratory compensated metabolic acidosis or alkalosis • Mixed acid-base abnormalities can involve ≥2 abnormalities.

PERIOPERATIVE RELEVANCE

• Patients commonly present to the operating room with disturbances in their acid–base equilibrium, or are at-risk for abnormalities that can increase morbidity and mortality such as: – Hyperventilation and hypoventilation – Anemia – Fluid loss – Malnutrition with low albumin – Hyperkalemia and hypokalemia – Gastric drainage • Conditions in which the physiologic buffer systems fail can demand therapeutic and pharmacologic interventions, requiring exact diagnosis of the nature of the acid–base disturbance. These include the following: – Blood gas analysis with pH, PCO2, [HCO3−], and base excess (BE). BE is the amount of acid or base needed to titrate the patient’s blood to a pH of 7.4. – Anion gap • THAM (trome thamine) can be used when patients are unable to exhale sufficient amounts of CO2 either spontaneously or with mechanical ventilation. About 30% of THAM has a pH

= 7.40 and is not ionized, being able to penetrate cells and act intracellularly. THAM actively binds hydrogen ions (H+) and cations of fixed or metabolic acids and increases bicarbonate. THAM is not recommended in patients with hyperkalemia or hyponatremia. • Sodium bicarbonate and THAM are equal in their ability to alkalinize; the latter is shorter lasting. Treatment of metabolic alkalosis focuses mainly on treating the underlying pathophysiologic problem. • Carbonic anhydrase inhibitors, which cause renal excretion of HCO3−, are also an option. EQUATIONS

• Henderson-Hasselbach equation; rectangular brackets indicate molar concentrations

pH = –log [H+]

pH = pK + log([HCO3−] / [CO2]) • Anion gap (AG): AG = Unmeasured anions – unmeasured cations = ([Na+] + [K+]) – ([Cl −] + [HCO −]) 3

REFERENCES

1. Casey JR. Why bicarbonate? Biochem Cell Biol. 2006;84(6):930–939. 2. Adrogué HJ, Gennari FJ, Galla JH, et al. Assessing acid-base disorders. Kidney Int. 2009;76:1239–1247.

3. Fidkowski C, Helstrom J. Diagnosing metabolic acidosis in the critically ill: Bridging the anion gap, Stewart, and base excess methods. Can J Anesth. 2009;56:247–256.

ADDITIONAL READING

• Falimirski ME. Civetta, Taylor, and Kirby’s critical care. Philadelphia: Wolters Kluwer/Lippincott Williams and Wilkins. • Rose BD, Post TW. Clinical physiology of acid-base and electrolyte disorders. New York: McGraw-Hill Medical Publishing Division.

See Also (Topic, Algorithm, Electronic Media Element) • Metabolic acidosis • Base excess

CLINICAL PEARLS

• Bicarbonate/CO2 is the most clinically relevant buffer system and is carefully regulated by

the pulmonary and renal systems. • Perioperatively, diagnosis and monitoring of acid–base excess involves clinical assessment and is aided by ABG draws (pH, HCO3−, and base excess).

• Treatment is aimed at the underlying cause and may be aided by exogenous bicarbonate or THAM; however, outcomes studies have not supported this practice.

BURNS

Naola Austin, MD Andreas Grabinsky, MD

BASICS DESCRIPTION

• Anesthesia providers are critical members of the multidisciplinary team that is required to treat patients with severe burn injuries, as well as burn reconstruction procedures. • Severe burns affect every organ system, present multiple medical and psychological challenges, and must be treated with prompt and vigilant care. EPIDEMIOLOGY Prevalence

In the US: 700,000/year; males: 70%, females: 30%; children <5 years: 17%; patients >60 years: 12% Prevalence

• Mild burns: 600/100,000 inhabitants • Severe burns: 5/100,000 inhabitants

Morbidity

Chronic pain, cosmetic consequences, contractures with resultant loss of limb function, longterm rehabilitation, need for repeat surgeries, and financial impact Mortality

• Overall mortality is 3.7% and increases with advancing age (age <16 years: 0.3–1.0%; age >80 years: 27.0%) • Increases with the total body surface area (%TBSA) affected • Increases with smoke inhalation injury

ETIOLOGY/RISK FACTORS

• Etiology: Fire/flame (41.6%); scald (31.0%; children are at a higher risk); contact with a hot object (8.8%); electrical (3.8%) • Circumstances of injury: Home (66%); accident, non-work related (66%); accident, work related (14.6%); accident, recreation (4.8%) PHYSIOLOGY/PATHOPHYSIOLOGY

• Severe inflammation has been implicated with many post-burn complications: Triggers loss of microvascular wall integrity, intravascular plasma and protein depletion, and interstitial edema (peak edema occurs at 24 hours). • Inhalation injury is direct damage to the upper and lower airways and lungs from heat,

smoke, or toxic fume inhalation. Inhalation of carbon monoxide produces carboxyhemoglobin, and inhalation of cyanide fumes causes inhibition of the mitochondrial electron transport chain.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• If inhalation injury or airway edema is suspected, secure the airway early before worsening edema makes intubation difficult or impossible. • Appropriate fluid management, maintenance of normothermia, glucose control, antibiotic prophylaxis, and ventilatory management have been shown to improve outcome in the ICU setting; these efforts should be extended perioperatively by the anesthesia provider.

PREOPERATIVE ASSESSMENT SYMPTOMS

Symptoms of inhalation injury: Voice change, dysphagia, dyspnea History

Etiology of burn injury, risk factors for inhalation injury (closed space, loss of consciousness), associated injuries, pre-existing medical conditions Signs/Physical Exam

• Signs of inhalation injury include singed eyebrows or nasal hair, facial burns, facial edema, carbonaceous sputum, respiratory distress, and inspiratory stridor. • Standard airway exam • Size of burned area (%TBSA)

TREATMENT HISTORY

• Airway management, intravenous access, fluids • Dialysis in patients with acute kidney injury; early continuous veno-venous hemofiltration may reduce 28-day mortality, acute lung injury severity, and respiratory distress (1). • Plasma exchange therapy may decrease the inflammatory response; this is still being investigated (2). • Blood transfusions; patients with comorbidities are more likely to receive blood, especially with small burn injuries (<10% TBSA) (3). However, this may increase infectious complications and mortality. Outcome studies have not provided information on the ideal transfusion paradigm with significant comorbidities. MEDICATIONS

• Naltrexone for pruritus may affect intraoperative opioid requirements. • TPN should be continued perioperatively; patients are hypermetabolic and have increased caloric requirements. • Sedation for intubated patients • Narcotics

DIAGNOSTIC TESTS & INTERPRETATION

Labs/Studies

• CBC • Complete metabolic panel • Coagulation panel • ABG for baseline acid–base status, lactate, and base deficit trends • Carbon monoxide and methemoglobin levels • Type and cross • Baseline chest radiography

CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular: Intravascular volume depletion, decreased systemic vascular resistance, myocardial depression, and deep vein thrombosis • Pulmonary: Pulmonary edema, impaired gas exchange, reduced chest wall and airway compliance, dysfunctional cilia, respiratory failure, PNA, and ARDS • Renal: Acute kidney injury • Hepatic: Congestion, fatty deposition, cholestasis, centrilobular necrosis, and activation of acute phase reactants • Gastrointestinal: Stress ulcers, decreased motility, ileus, decreased absorption, bacterial translocation, edema, abdominal hypertension, and compartment syndrome • Musculoskeletal: Acute and chronic wasting, contractures • Neuroendocrine: Hypermetabolism increases catecholamines and catabolic hormones, oxygen demand, production of carbon dioxide, muscle wastage, and glucose derangements. CIRCUMSTANCES TO DELAY/ CONDITIONS

The need to treat carbon monoxide poisoning with hyperbaric oxygen should be weighed against the need for emergent surgery. CLASSIFICATIONS

• Degrees of burn: – First-degree, superficial burn extends into epidermis, blanches, does not blister, and is intensely painful. – Second-degree, superficial partial-thickness burn extends into superficial or papillary dermis, blanches, blisters, and is severely painful. – Second-degree, deep partial-thickness burn extends into deep or reticular dermis, does not blanch or blister, and is less painful. – Third-degree, full-thickness burn extends into subcutaneous tissue or deeper, is dry like leather or white, and is minimally painful. • Extent of burn: – Wallace’s Rule of Nine can be used to estimate the %TBSA burned in adults. – The Lund–Browder chart can be used to estimate %TBSA in children. • ABA grading system: – Minor burns: <10% TBSA in adults, <5% TBSA in children or elderly patients, <2% fullthickness burn – Moderate burn: 10–20% TBSA in adults, 5–10% TBSA in children or elderly patients, 2– 5% full-thickness burn; high-voltage burn, circumferential burn, suspected inhalation

injury, concomitant medical problems – Major burn: >20% TBSA in adults, >10% TBSA in children or elderly, >5% fullthickness burn, high-voltage burn, known inhalation injury; any significant burn to face, eyes, genitalia, joints or significant associated injuries

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines or ketamine may relieve anxiety and decrease opiate requirements. • Dexmedetomidine has been shown to improve the level of sedation compared to benzodiazepines in burn patients in the ICU (4).

Special Concerns for Informed Consent

• If unable to provide informed consent, a legal next of kin or 2 physicians’ consent may be required for urgent treatment. • Patients with severe burns to the head or neck may be impossible to intubate and can require a surgical airway. INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia is required for most burn injury patients; however, regional anesthesia is an option in selected cases. Monitors

• Standard ASA monitors • Intra-arterial blood pressure; femoral artery cannulation is often used in pediatric patients. There is a 1.9% incidence of lost pulses, some requiring thrombectomies; monitoring of distal pulses should be performed to avoid critical ischemia (5). • Core temperature • Foley catheter • Vascular access: Place large-bore IV catheters in non-burned areas whenever possible; most patients will require central venous access once stabilized; intraosseous access is acceptable for primary resuscitation. Induction/Airway Management

• Early rapid-sequence intubation or awake fiberoptic intubation may be the safest approach in patients with inhalation injury or airway edema. • Succinylcholine can be used during the first 48 hours following burn injury. It should not be used after the initial 48 hours or within 1 year of burn injury (extrajunctional receptor proliferation). • Non-depolarizing muscle relaxants are safe in burn injury patients.

Maintenance

• Prophylactic antibiotics; the impairment of physical barriers and an immune-compromised state increase the likelihood of infection (Pseudomonas aeruginosa is common). • Inhalational anesthesia or TIVA is appropriate. • Ventilation: High FIO2 in patients with carbon monoxide poisoning. High-frequency

oscillatory ventilation has been shown to improve oxygenation with concurrent ARDS; consider utilizing an ICU ventilator intraoperatively. • Fluid resuscitation to treat burn shock, maintain hemodynamic stability and urine output – Parkland formula: Lactated Ringer’s 4 mL/kg/%TBSA over 24 hours with half in the first 8 hours and the remaining half over the next 16 hours – Modified Brooke formula: Lactated Ringer’s 2 mL/kg/%TBSA over 24 hours – Children <20 kg: Lactated Ringer’s 3 mL/kg/%TBSA over 24 hours plus hourly maintenance thereafter (4 mL/kg for the first 10 kg + 2 mL/kg for next 10 kg + 1 mL/kg) – Over-resuscitation or “fluid creep” can exacerbate pulmonary edema, chest wall edema, or compartment syndrome of limbs or abdomen. Colloids have not been shown to improve clinical outcomes (6)[A]. – Following inhalation injury, the 24-hour fluid requirement increases (6)[A], (7)[A]. Central venous pressures and urine output can aid with management. • Avoid hypothermia; intraoperative hypothermia during burn excision has been linked to the development of postoperative lung inflammation. Decreases of >1°C demonstrated increased neutrophils 24 hours postsurgery compared to normothermics (8). • Monitor hemoglobin, electrolytes, coagulation, as well as acid–base status. • High-dose opiates for analgesia; the increased volume of distribution reduces drug concentrations. • Local anesthetic infiltration is often used with epinephrine to reduce blood loss. • Tight glucose control (blood sugars <150 mg/dL) and decreased variability have a decreased sepsis rate and mortality in ICU patients (9). Efforts should be continued perioperatively by the anesthesia provider.

Extubation/Emergence

Patients with severe burns and/or inhalation injury are likely to remain intubated after surgery and in the ICU during the acute post-burn injury period. Studies have shown that they have a significantly higher rate of failed extubation; 30% compared to the general ICU population (10)[B].

FOLLOW-UP BED ACUITY

Transfer to a burn center is indicated for: Age <5 years or >60 years; burns to the face, hands, perineum, joints, or other areas of function; >15% TBSA partial-thickness or >5% full-thickness burn; inhalation injury; chemical, high voltage; concomitant trauma. MEDICATIONS/LAB STUDIES/CONSULTS

Severe burn injury is a permanent, life-altering experience for the patient and his or her

family and requires a multimodal approach and often long-term support: Pain specialists, rehabilitation medicine specialists, plastic surgeons, psychiatrists, physical therapists, social workers, and financial counselors. COMPLICATIONS

Pneumonia (3%), urinary tract infection (2%), wound infection (2%), respiratory failure (3%), septicemia (2%), cellulitis (1.5%), renal failure (1%)

REFERENCES

1. hung KK, Lundy JB, Matson JR, et al. Continuous veno-venous hemofiltration in severely burned patients with acute kidney injury: A cohort study. Crit Care. 2009;13:R62.

2. Klein MB, Edwards JA, Kramer CB, et al. The beneficial effects of plasma exchange after severe burn injury. J Burn Care Res. 2009;30:243–248. 3. Boral L, Kowal-Vern A, Yogore M, et al. Transfusions in burn patients with/without comorbidities. J Burn Care Res. 2009;30:268–273.

4. Talon MD, Woodson LC, Sherwood ER, et al. Intranasal dexmedetomidine premedication is comparable with midazolam in burn children undergoing reconstructive surgery. J Burn Care Res. 2009;30:599–605. 5. Mourot JM, Oliveira HM, Woodson LC, et al. Complications of femoral artery catheterization in pediatric burn patients. J Burn Care Res. 2009;30:432–436. 6. Saffle JR. The phenomenon of “fluid creep” in acute burn resuscitation. J Burn Care Res. 2007;28(3):382–395. 7. Latenser BA. Critical care of the burn patient: The first 48 hours. Crit Care Med. 2009;37(10):2819–2826. 8. Oda J, Kasai K, Noborio M, et al. Hypothermia during burn surgery and postoperative acute lung injury in extensively burned patients. J Trauma. 2009;66:1525–1529. 9. Pidcoke HF, Salinas J, Wanek SM, et al. Glucose variability is associated with high mortality after severe burn. J Trauma. 2009;67:990–995. 10. Smailes ST, Martin RV, McVicar AJ. The incidence and outcome of extubation failure in burn intensive care patients. J Burn Care Res. 2009;30(3):393–394. See Also (Topic, Algorithm, Electronic Media Element) • Smoke inhalation injury • Operating room fires • Airway sires • Acute respiratory distress syndrome (ARDS)

CODES ICD9 949.0 Burn of unspecified site, unspecified degree

ICD10

T30.0 Burn of unspecified body region, unspecified degree

CLINICAL PEARLS

• Consider anesthesia “stand by” for extubation and the possibility of extubating over a small tube exchanger to facilitate re-intubation.

BURR HOLE Dirk Younker, MD

BASICS DESCRIPTION General

• Burr hole craniotomy is a minimally invasive form of an ancient surgical procedure known as “trephination.” • It is performed to drain epidural (EDH) or subdural (SDH) hematomas, which may be either acute or chronic in nature. • The scalp is reflected over the area of the hematoma to expose the skull, followed by the use of a drill to create the hole. • In the case of an epidural clot, coagulum is simply removed and the wound is closed; clot expansion tends to be restrained by the compartments formed by dura adherent to cranial sutures. • For SDHs, the dura is incised, as clot can be diffuse due to the lack of septations in the subdural space. Irrigation may be used to remove the hematoma; a drain may be placed to allow for postoperative drainage. • In extreme, life-threatening conditions, burr holes may be performed with a simple, handpowered, manual twist drill. Position

• Supine with the operating table turned 90 or 180°, depending on surgical preference and physical layout of the OR • The patient’s face points to the ceiling if a frontal incision is used. Alternatively, the patient’s face is turned to the anesthesia team if a right or left temporal incision is performed. Mayfield pins are often used, but the head may also be rested upon sterile towels. • Rarely, prone position may be required for infratentorial exposure (cerebellar clot).

Incision

• Scalp incision in the frontal, temporal, or base of skull • Small, dime-sized hole made with twist drill or power drill • 80% of acute EDHs are located below an existing fracture line. • Incision may or may not be irrigated or drained (1)[A]. Approximate Time

60 minutes; longer if substantial bleeding is encountered EBL Expected

Minimal, unless the patient is coagulopathic

Hospital Stay

• 23-hour admission for serial neurologic examinations, perhaps longer depending on comorbidities • Repeat, post-procedural CT scans are common in those patients with abnormal baseline neurologic status (e.g., a demented patient from a nursing home).

Special Equipment for Surgery

• Manual, hand-twist drill • Power drill • Occasionally, endoscopic visualization is employed in nonemergent situations.

EPIDEMIOLOGY Incidence

Acute post-traumatic SDH and EDH: 0.83/100,000 population Prevalence

• Acute post-traumatic SDH and EDH: Median age 45 years, 80% male • Chronic SDH: Median age 60 years; male:female ratio 5.63:1

Morbidity

• Acute post-traumatic SDH and EDH: 63% good outcome at 6 months • Chronic SDH: 95.6% good outcome following surgery (most surgeries performed under local anesthesia with sedation)

Mortality

Acute post-traumatic SDH and EDH: 23% mortality, greatest likelihood of death if age >60 AND surgery for acute SDH (2)[A], (3)[A] ANESTHETIC GOALS/GUIDING PRINCIPLES

• Acute post-traumatic SDH and EDH: – Patients may have an increased risk of aspiration – Cervical and thoracic spine precautions must be maintained for patients with multiple trauma – The traumatized brain needs oxygen and an adequate perfusion pressure (maintain oxygenation, ventilation, and blood pressure) – The need for optimum preoperative assessment and monitoring needs to be weighed against the need for expeditious decompression when speed is of the essence

PREOPERATIVE ASSESSMENT SYMPTOMS

• Headache • Somnolence (sleepiness) • Localizing neurologic signs

History

• Head trauma • Anticoagulant therapy • Acquired disorders of hemostasis NOT involving anticoagulant therapy (e.g., TTP) • Concomitant drug or alcohol use • Tobacco use (these patients may have significant carboxyhemoglobin levels and may also cough upon emergence) Signs/Physical Exam

• Trauma (especially orofacial trauma with cervical collar present) • Focal neurologic signs • Obtundation • In elderly patients, look for signs of a pacemaker or an AICD.

MEDICATIONS

• Anticoagulants • Drugs which inhibit the metabolism of warfarin compounds (INH, amiodarone, metronidazole, omeprazole) DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hematocrit, platelet count, INR • Creatinine, blood glucose, LFTs • A type and screen should be available if one anticipates the need for component therapy. • EKG or CXR may be helpful in stable patients with multiple comorbidities. • In deteriorating patients, the anaesthetist may need to progress without any laboratory studies at all and obtain them intraoperatively later. CONCOMITANT ORGAN DYSFUNCTION

• Renal dysfunction may prolong the activity of anticoagulants, in particular clopidogrel. • Liver dysfunction may alter warfarin metabolism. • Hypothermia may complicate the emergence from a general anesthetic as well as impair coagulation. • Pre-existing hypertension may accentuate emergence hypertension.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Doses of premedicants must NOT be so large as to obscure the neurologic exam or depress spontaneous ventilation; a minimalist approach is best. • Acid aspiration prophylaxis is warranted in those patients who have not fasted.

Special Concerns for Informed Consent

• Urgency of surgery may preclude truly informed consent. • Patients with chronic SDHs may have a long-standing abnormal neurologic examination which will preclude their giving informed consent themselves; a surrogate may be needed.

Antibiotics/Common Organisms

• Usually, coverage for common skin flora is sufficient. • In trauma patients with dirty wounds, polymicrobial coverage is warranted.

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia for the multiple trauma patient or the uncooperative patient • Cooperative patients with chronic SDH may be managed with a scalp block and judicious intravenous sedation.

Monitors

• Standard ASA monitors • Invasive arterial and central venous monitoring may be warranted in some high-acuity patients.

Induction/Airway Management

• Thiopental, propofol, or etomidate is chosen on the basis of the patient’s hemodynamic status. • Rapid-sequence induction with succinylcholine and cricoid pressure may be indicated. • Esmolol may be used to attenuate the sympathetic response to laryngoscopy and intubation. • Scalp block and intravenous sedation in selected patients who are cooperative and who have fasted; a remifentanil or dexmedetomidine infusion may be considered (4)[A].

Maintenance

• Inhalational or intravenous anesthesia, or both may be utilized. • Sedation may be maintained with an infusion of remifentanil or dexmedetomidine.

Extubation/Emergence

• Awake extubation should be performed if the patient is considered a “full stomach”; intravenous lidocaine and esmolol may be useful in the suppression of coughing and emergence hypertension, respectively. • Insertion of an LMA or a deep extubation may be considered in selected patients who have fasted, to avoid coughing and bucking.

POSTOPERATIVE CARE BED ACUITY

• Elderly patients with multiple comorbidities or those patients with severe coexisting trauma may require ICU admission and postoperative ventilation. • Most patients can be discharged to a floor where the nursing personnel can perform repeat

neurologic examinations (“neuro-checks”).

ANALGESIA

• Postoperative pain tends to be managed well with small doses of IV or PO opiates. • Reliance upon large doses of opiates for postoperative pain management may obscure the neurologic examination or accentuate the nausea to which these patients are already prone.

COMPLICATIONS

• Re-accumulation of clot • Lingering neurologic deficits • Malignant cerebral edema • Wound infections • Injury to the brain

PROGNOSIS

Return to baseline neurologic function is expected if surgery has been expeditious and without complications, in particular for chronic SDH.

REFERENCES

1. Donovan DJ, Moquin RR, Ecklund JM. Cranial burr holes and emergency craniotomy: Review of indications and technique. Military Med. 2006;171(1):12–19. 2. Tallon JM, Ackroyd-Stolarz S, Karim SA, et al. The epidemiology of surgically treated acute subdural and epidural hematomas in patients with head injuries: A population-based study. Can J Surg. 2008;51(5):339–345. 3. Yuan L, Xia J, Wu A, et al. Burr-hole craniotomy treating chronic subdural hematoma: A report of 398 cases. Chin J Traumatol. 2010;13(5):265–269. 4. Frost EAM, Booij LHDJ. Anesthesia in the patient for awake craniotomy. Curr Opin Anaesthesiol. 2007;20:331–335. 5. Weigel R, Schmiedek P, Krauss JK. Outcome of contemporary surgery for chronic subdural haematoma: Evidence-based review. J Neurol Neurosurg Psychiatry. 2003;74:937–943.

CLINICAL PEARLS

• In the patient who is rapidly deteriorating, insertion of intra-arterial catheters and supplemental intravenous catheters can wait until AFTER the operating table is turned. • Plasma levels of local anesthetics can reach high levels following scalp block; patients rarely become symptomatic. • Although very rare, chronic SDHs can occur in the healthy postpartum patient, almost always following dural puncture. • Burr holes are appropriate for both the pediatric and adult population. Studies have demonstrated that results are better than a formal craniotomy for drainage of chronic SDH (5)[A].

BURST SUPPRESSION Victor Duval, MD

BASICS DESCRIPTION

• The burst suppression (BS) pattern on electroencephalogram (EEG) was first demonstrated in 1936 by Derbshire et al. in response to anesthetics. The term “burst suppression” was introduced by Swank and Watson in 1948 in experiments studying the effects of barbiturates on EEG patterns in various areas of the brain. • BS is a periodic pattern of high-voltage, slow, sharp, spiking complexes that are interspersed by low-voltage (<10 mV) complexes or isoelectric periods. • At present, BS is usually induced with barbiturates or other anesthetics in order to decrease cerebral metabolic activity in the setting of focal ischemia or status epilepticus. PHYSIOLOGY PRINCIPLES

• Neuronal electrical activity accounts for 50–60% of the brain’s oxygen consumption. Thus, suppression of electrical activity with anesthetic and sedative medications can help restore a favorable balance between oxygen delivery and consumption. • Technique: EEG can be monitored with as little as 1 lead in the OR or a full EEG in the ICU. In the ICU, it can be performed by an anesthesiologist or neuromonitoring team. An amplitude-integrated EEG (aEEG) is used to simplify long-term monitoring of brain function. It filters the EEG and displays it on a compressed time scale, providing a simplified method to monitor brain activity. • BS is defined as a burst of slow, sharp, and spiking activity followed by reduced or suppressed electrical activity. There is no universal standard; however, most clinicians aim for an interburst interval of about 10 s. ANATOMY

• Barbiturates bind to the GABAA receptor (a chloride ion channel) and potentiate the effect of GABAA neurotransmitter. This results in chloride ion entry into the cell and

hyperpolarization; the action potential of postsynaptic neurons is increased and neuronal signaling activity is decreased. • Inhaled anesthetic agents inhibit excitatory neurotransmission and potentiate inhibitory receptors and ion channels. This leads to decreased oxygen requirements and ATP production associated with signaling activity. • It has been proposed that the thalamus generates a “fundamental brain-rhythm,” which is relatively resistant to the effects of anesthetics. Modern agents act primarily on the cerebral cortex; thus, the characteristic BS pattern emerges at this site before thalamic suppression.

DISEASE/PATHOPHYSIOLOGY

• Hypothermia: Therapeutic hypothermia (TH) following adult cardiac arrest alters prognostic

accuracy. Monitoring the EEG for BS can aid with predicting outcome and titrating temperature; the presence of BS is associated with unfavorable outcomes. • Encephalopathy: Burst suppression is characteristic of early myoclonic encephalopathy (EME) and Ohtahara syndrome—2 rare and devastating CNS disorders of infancy. – EME is characterized by erratic myoclonic activity. Simple partial seizures, general myoclonus, and tonic spasms can also occur. Severe developmental delay, marked hypotonia, and altered level of consciousness are consistent findings. Some patients deteriorate into a vegetative state. – Ohtahara syndrome is a precursor to West Syndrome and Lennox–Gastaut syndrome. Frequent tonic spasms appear in the 1st month of life and partial motor seizures may occur. Marked developmental delay and intractable epilepsy are common in patients who survive beyond infancy. • Premature infants – Intracranial hemorrhage: BS with low voltage has a 100% positive predictive value although a lower negative predictive value. – Hypoxia/asphyxia: The presence of BS suggests a poor prognosis.

PERIOPERATIVE RELEVANCE

• Induced BS: The BS pattern on EEG can be used clinically to titrate general anesthetics to their maximally effective dose, as well as for any procedure where there is a chance of focal brain ischemia (e.g., aneurysm clipping, carotid endarterectomy, large intracranial masses, etc.). However, a growing body of evidence suggests that BS doses of anesthetics, especially barbiturates, are not necessary for optimal brain protection. – Barbiturates: Drug metabolism is slowed at levels required to achieve BS and it may take several hours for the patient to emerge. This typically requires postoperative intubation/continued ventilatory support and delays neurologic examination. Consequently, this technique has fallen out of favor in modern neurosurgical anesthesia. – Can be induced with any inhaled or intravenous induction agent; however, evidence of brain protection is only available with isoflurane and barbiturates. • Seizure treatment: Seizure activity is characterized by an abnormal increase in electrical activity that increases the demand for oxygen. This can quickly lead to ischemia. Decreasing oxygen consumption can effectively protect neurons from injury. • Incomplete cerebral ischemia: In this setting, areas of the brain adjacent to the ischemic region (penumbra) may be subject to low oxygen concentrations. Since neurons in the penumbra remain intact immediately after an infarct, decreasing their oxygen demand can limit the extent of neurologic injury • Global ischemia: Anesthetic-induced BS following global ischemia, such as in cardiac arrest, has not been shown to improve neurologic outcome since brain autoregulation remains intact and the oxygen requirements to maintain electrical activity do not increase. • BIS: Only the EEG pattern on the BIS may be correlated; BS does not correlate with any particular BIS number.

GRAPHS/FIGURES

FIGURE 1. Burst suppression is characterized by a periodic pattern of high-voltage, slow, sharp, spiking complexes that are interspersed by low-voltage complexes or isoelectric periods.

REFERENCES

1. Chalak LF, Sikes NC, Mason MJ, et al. Low-voltage aEEG as predictor of intracranial hemorrhage in preterm infants. Pedtiatr Neurol. 2011;44(5):364–369. 2. Derbyshire AJ, Rempel B, Forbes A, et al. The effects of anesthetics on action potentials in the cerebral cortex of the cat. Am J Physiol. 1936;116:577–596. 3. Drummond J. Brain protection during anesthesia: A reader’s guide. Anesthesiology. 1993;79:877–880. 4. Henry CE, Scoville WB. Suppression-burst activity from isolated cerebral cortex in man. EEG Clin Neurophysiol. 1952;1:1–22. 5. Judy-Fray F, Kroeger D, Oana C, et al. Cortical inhibition during burst suppression induced with isoflurane anesthesia. J Neurosci. 2009;29:9850–9860. 6. Niedermeyer E. The burst-suppression electroencephalogram. Am J Electroneuro-diagnostic Technol. 2009;49:333–334. 7. Oddo M, Rossetti AO. Predicting neurological outcome after cardiac arrest. Curr Opin Crit Care. 2011;17(3):254–259. 8. Swank RL, Watson CW. Effects of barbiturates and ether on spontaneous electrical activity of dog brain. J Neurophysiol. 1949;12:137–160. See Also (Topic, Algorithm, Electronic Media Element)

• Cerebral aneurysm clipping • Electroencephalogram (EEG) • Carotid endarterectomy

CODES ICD9 794.02 Nonspecific abnormal electroencephalogram [EEG] ICD10

R94.01 Abnormal electroencephalogram [EEG]

CLINICAL PEARLS

• The burst suppression pattern on EEG can be used to determine maximal effector site concentration of various anesthetics used in general anesthesia. • Pharmacologic suppression of cortical electrical activity may be beneficial in protecting the brain after focal ischemia but has no neuroprotective effects following global ischemia. • Intravenous anesthetic agents, such as barbiturates, propofol, and etomidate, may be used to decrease ICP secondary to traumatic brain injury, but they have not been shown to decrease the extent of neurologic injury.

CARBON DIOXIDE ABSORBERS Swarup S. Varaday, MBBS, FRCA, FCARSI

BASICS DESCRIPTION

• Carbon dioxide (CO2) absorbers function to remove exhaled carbon dioxide from anesthesia

breathing systems at low fresh gas flow rates. They make rebreathing of exhaled volatile agents and oxygen possible and thus conserve anesthetic agents and reduce pollution to the environment. • Absorbents – Contain a chemical mixture of alkali metal hydroxides. – Are used in closed and semi-closed circle breathing systems. – Are contained in clear plastic containers to allow visualization of indicator color change. – Are available as a single canister, two canisters (placed one over the other in series), or as pre-filled plastic disposable cartridges. • Current absorbents include – Soda lime – Calcium hydroxide lime (Amsorb); does not degrade inhalational agents to compound A (a toxic breakdown product of sevoflurane) or carbon monoxide (CO). – Barium hydroxide lime (Baralyme); was discontinued in late 2004 due to reports of extreme heat and incidents of fire when desiccated absorbent was exposed to sevoflurane. • Rebreathing of CO2 can result in hypercarbia and respiratory acidosis. PHYSIOLOGY PRINCIPLES

• Carbon dioxide is the gaseous waste product of body metabolism that is exhaled into anesthesia breathing circuits. Absorbents eliminate CO2 from breathing circuits, thereby preventing rebreathing and hypercarbia. • An ideal CO2 absorbent is

– Non-toxic – Does not interfere with anesthetic agents – Has good CO2 absorption capacity

– Economical – Easy to handle • Soda lime – Composition by weight: 80% calcium hydroxide, 15% water vapor, 4% sodium hydroxide, 1% potassium hydroxide. – Setting (hardness) agent: Silicates; they also reduce dust formation. – Capacity: 26 L of CO2 per 100 g of absorbent. Absorption capacity can decrease to 10–20 L or less when gases are channeled through low resistance areas.

– Method: Absorbs and neutralizes CO2.

– Absorption involves the following: CO2 + H2O H2CO3 + H2O H+ HC3-

HCO3− + Ca++ yields calcium carbonate and HCO3− + Na+ yields sodium carbonate

Sodium carbonate reacts with calcium hydroxide to form sodium hydroxide Sodium hydroxide is more soluble and chemically more active than calcium hydroxide. It is also responsible for soda lime’s “regeneration reaction.” Regeneration can occur when soda lime is set aside for several hours, usually overnight and then used again; it has less absorptive capacity and is more rapidly depleted. – Neutralization is an exothermic reaction that occurs only in the presence of water vapor in the granules. It has been calculated that the heat produced by the neutralization of each gram molecule of CO2 (44 g) amounts to 13,700 calories. During this chemical reaction

water is liberated. • Amsorb – Composition by weight: Consists primarily of calcium hydroxide and calcium chloride; does not contain strong alkalis. – Setting agent: Small amounts of calcium sulfate and polyvinyl pyrrolidone. • Baralyme – Composition by weight: Approximately 20% barium hydroxide and 80% calcium hydroxide. – Setting agent: Most of the moisture is present in the form of water of crystallization and not as a film on the surface of the granules. • pH Indicator is added to signal when the absorptive capacity of the material has been consumed. Ethyl violet (pKa 10.3) is present in all absorbents in the US; when the pH changes secondary to CO2 absorption, it changes from colorless to violet. However, prolonged exposure to fluorescent lights can produce photo deactivation of the dye; this results in a white appearing absorbent, despite decreased pH and absorptive capacity. • Shape and size of granules. The goal is to maximize surface area without increasing resistance and work of breathing. To that extent, granules are: – Porous – Not too large (otherwise would reduce the surface for absorption) – Not too small (otherwise would increase the resistance to breathing) – Granule size is measured by a mesh number. Soda lime consists of granules in the range of 4–8 mesh. A 4 mesh granule is able to pass through sieves that have 4 openings per linear inch, and an 8 mesh granule is able to pass through sieves that have 8 openings per linear inch.

DISEASE/PATHOPHYSIOLOGY

• Rebreathing of CO2 with resultant hypercarbia

– Occurs when absorbent is exhausted, channeling of gases increases circuit dead space, or a leak in the canister assembly or incompetent one-way valves cause rebreathing of CO2.

– Can increase sympathetic drive with resultant increases in BP and heart rate (increased

surgical bleeding), skin flushing, sweating, and tachyarrhythmias. • Carbon monoxide. Volatile agents that contain a difluoromethoxy moiety can react with conventional CO2 absorbents and generate CO gas. Clinically significant CO generation only

occurs if the absorbent is absolutely dry. Desflurane > enflurane > isoflurane > sevoflurane. • Sevoflurane reacts chemically with desiccated Baralyme or soda lime to produce CO and flammable organic compounds, including methanol and formaldehyde. The reaction produces heat that increases the rate of sevoflurane breakdown. Sevoflurane may be so extensively consumed that maintaining an adequate depth of anesthesia becomes difficult.

PERIOPERATIVE RELEVANCE

• An exhausted soda lime canister does not feel warm and changes from colorless to violet. • Loose packing of soda lime granules in a canister can cause channeling of gases and decrease CO2 absorption (increased dead space). If the granules are too tightly packed, it may increase the resistance to breathing. • Rebreathing and hypercarbia can be detected by steady increases in the end-tidal CO2 (EtCO2) concentration. Blood gas analysis may show respiratory acidosis.

• Excessive heating. Rapid changes in the color of some CO2 absorbents or an unusually

delayed rise in the delivered (inspired) gas concentration of sevoflurane (compared with the vaporizer setting) may indicate excessive heating of the CO2 absorbent canister and

chemical breakdown of sevoflurane. Extremely rare cases of spontaneous fire in the respiratory circuit have been reported with sevoflurane and desiccated CO2 absorbent.

• Carbon monoxide cannot be detected using routine anesthesia gas monitoring; it has the same molecular weight as nitrogen (present in air). CO symptoms can be masked by general anesthesia and pulse oximetry cannot distinguish between carboxyhemoglobin and oxyhemoglobin. Blood co-oximetry can detect carboxyhemoglobin levels. • Improperly fixed canister gaskets and defective prepacks larger than factory specifications have been reported to cause leaks in the breathing circuits. • Prepacked disposable canisters also cause total obstruction of the circle system if the clear plastic shipping wrapper is not removed prior to use (6). This can result in high airway pressures and difficulty with ventilation. The airway pressure may still appear high even on disconnecting the breathing circuit from the patient but is easy to ventilate the patient with an AMBU bag. • Check that canisters are fitting well in canister housing and for leaks to prevent rebreathing. • The new CO2 absorbent Amsorb does not contain strong bases like sodium and potassium hydroxides. This eliminates the undesirable production of CO and the nephrotoxic substance compound A. It may also reduce the possibility of fire in the breathing circuits. Amsorb has less absorptive capacity than strong base containing absorbents and is more expensive.

REFERENCES

1. Yamakage M, Takahashi K, Satoh JI, et al. Performance of four carbon dioxide absorbents in experimental and clinical settings. Anesthesia. 2009;64(3):287–292.

2. Wissing H, Kuhn I, Warnken U, et al. Carbon monoxide production from desflurane, enflurane, halothane, isoflurane and sevoflurane with dry soda lime. Anesthesiology. 2001;95:1205–1212. 3. Laster MJ, Egler El 2nd. Temperatures in soda lime during degradation of desflurane, isoflurane and sevoflurane by dessicated soda lime. Anesth Analg. 2005;101(3):753–757. 4. Baum JA, Woehlck HJ. Interaction of inhalation anesthetics with CO2 absorbents. Best Pract Res Anesthesiol. 2003;17(1):63–76. 5. Kharasch ED, Powers KM, Artru AA. Comparison of Amsorb, sodalime, and Baralyme degradation of volatile anesthetics and formation of carbon monoxide and compound A in swine in vivo. Anesthesiology. 2002;96(1):173–182.

6. Norman PH, Daley MD, Walker JR, Fusetti S. Obstruction due to retained carbon dioxide absorber canister wrapping. Anesth Analg. 1996;83(2):425–426.

7. Bagdasarian LA, Shah NK, Sharif MK. Carbon dioxide absorber as a cause of high airway pressures. J Clin Anesth. 2008;20(1):48–49. See Also (Topic, Algorithm, Electronic Media Element) • Breathing circuit • Carbon monoxide poisoning • Respiratory acidosis

CLINICAL PEARLS

• Carbon dioxide absorbers prevent rebreathing of CO2 and development of hypercarbia and

respiratory acidosis. • In patients under general anesthesia, detection of inspired CO2 (iCO2) and a steady increase in EtCO2, despite increasing minute ventilation, is suggestive of rebreathing. This may be

due to exhaustion of the absorbent (detected by change in absorbent color to violet, canister not warm to touch) or a defect in the expiratory valve. Other causes of increased metabolism (e.g., malignant hyperthermia and thyroid storm) should also be considered and ruled out. • Desiccation of the absorbent can be avoided by – Consistent use of low-flow techniques – Routine change of the absorbent at least weekly – Labeling the canisters with the filling date – Carefully closing all gas flow controls after each anesthetic is complete – Avoiding drying out the breathing system or the anesthetic ventilator overnight by leaving a continuous flow of gases that may pass through the canister.

CARBON DIOXIDE TRANSPORT IN BLOOD Melissa Flanigan, DO

BASICS DESCRIPTION

• Carbon dioxide (CO2) is a by-product of cellular metabolic pathways. Rapid diffusion of CO2 from cells into capillaries occurs despite a partial pressure of only 1–6 mm Hg, compared with ∼64 mm Hg for oxygen. • CO2 is transported through the blood to alveoli for excretion in three different forms: – Dissolved in blood – Carbamino compounds – Bicarbonate ion

PHYSIOLOGY PRINCIPLES

• At a cardiac output of 5 L/min, each 100 mL of blood passing through the lungs unloads 4–5 mL of CO2. The amount circulating is a function of both CO2 elimination and production. • Transport to the lungs occurs in three different forms; the sum comprises the total CO2

content of blood. The three forms are as follows: – Physically dissolved in plasma solution (7%). CO2 is 20 times more soluble than oxygen

and results in the rapid transfer between tissues, blood, and the alveoli. Dissolved CO2 increases linearly with increases in PaCO2.

– Carbamino compounds (13%). CO2 can enter the erythrocyte and reversibly bind with

nonionized terminal amino groups of blood-borne proteins. The resulting compound is called carbaminohemoglobin. The Haldane effect facilitates the passage of CO2 in the blood and excretion by the alveoli. In tissue, deoxyhemoglobin’s increased affinity to CO2 (3.5 times greater) results

in effective uptake. In the pulmonary capillaries, oxyhemoglobin’s reduced affinity to CO2 results in “off-loading” and excretion. This liberates CO2 that then diffuses from

pulmonary capillary blood into alveoli. – Bicarbonate (80%) CO2 enters the erythrocyte where it reacts with water to form carbonic acid. This

reaction is almost immediate in the presence of the enzyme carbonic anhydrase: H2O +

CO2 ←→ H2CO3 ←→ H+ + HCO3− (Note: this enzyme is absent in plasma). Most of

the hydrogen ions combine with hemoglobin, a powerful buffer. Buffering capacity. Bicarbonate is considered the most important buffer in extracellular fluid. It provides immediate and effective chemical buffering against metabolic acid– base disturbances. If a strong acid is added to the extracellular fluid, bicarbonate reacts

with the H+ to produce CO2.

Chloride effect: Occurs in the venous side of capillaries. Bicarbonate ions diffuse from erythrocytes into plasma, accompanied by the opposite movement of chloride ions into the cells to maintain electrochemical neutrality (chloride shift). The increase in osmotically active ions (chloride and bicarbonate) in venous erythrocytes encourages the entry of water, thus increasing their volume. This explains why the venous hematocrit is ∼3% higher than the arterial hematocrit. • The kidneys indirectly affect CO2 homeostasis through its ability to control the amount of HCO3− reabsorbed from filtrated tubular fluid, form new HCO3−, and eliminate H+ in the form of titratable acids and ammonium ions. – HCO3- is filtered at the glomerulus.

Approximately 85% is reabsorbed at the proximal tubules. After diffusing into the renal tubular cell, CO2 combines with water to form carbonic acid (in the presence of carbonic anhydrase). Carbonic acid rapidly dissociates into H+ and HCO3-; the bicarbonate ion

enters the bloodstream while H+ is secreted into the renal tubule. HCO3- that is not reabsorbed may bind with H+ within the lumen to form carbonic acid.

Carbonic anhydrase on the luminal brush border catalyzes the dissociation of H2CO3 into

CO2 and H2O. This CO2 replaces the CO2 that was utilized in the renal tubular cell.

• Correction of the imbalance between production and elimination of CO2 takes about 30

minutes. Central chemoreceptors respond rapidly to a change in hydrogen ion concentration (which is affected by the arterial CO2 content), while peripheral chemoreceptors respond to the arterial content of oxygen.

Pediatric Considerations

• The fetus is dependent on the placenta for respiratory gas exchange. CO2 easily diffuses

across the placenta and is aided by maternal hyperventilation, which increases the gradient for the transfer from the fetus into the maternal circulation. • At birth, respiratory efforts occur within 30 seconds and are sustained to correct the hypoxia and mild acidosis that occurs during the birthing process. Increases in oxygen tension cause the release of chemical mediators that convert the fetal circulation to an adult circulation. • Fetal hemoglobin (HbF) has a very high affinity for oxygen, which facilitates transfer of oxygen from the placenta to the fetus. However, after birth the usefulness of HbF is limited due to its impaired oxygen release to the tissues. It is replaced by adult hemoglobin by 4–6 months of age. HgF in the newborn has a reduced ability to carry and transport CO2. • Pediatric renal function is diminished until about age 2. Premature neonates possess multiple renal defects, including impaired bicarbonate reabsorption.

Pregnancy Considerations

Maternal hyperventilation results in reductions in P2 to ∼30 Hg. However, the compensatory

decrease in plasma bicarbonate concentration results in only a mild respiratory alkalosis

ANATOMY

• PaCO2 in alveoli • PaCO2 in tissue

DISEASE/PATHOPHYSIOLOGY

• Imbalances in CO2 homeostasis can result in respiratory acidosis (pH <7.4) or alkalosis (pH >7.4). Deviations can have adverse consequences and be deleterious. • Respiratory acidosis occurs when there is alveolar hypoventilation or increased metabolism, leading to the accumulation of CO2 and carbonic acid formation.

• Respiratory alkalosis occurs when the PaCO2 is decreased: The most likely perioperative

cause is iatrogenic hyperventilation, which can be corrected by ventilator setting adjustments. Alkalosis is a normal occurrence with pregnancy; there is a 50% increase in alveolar ventilation.

Geriatric Considerations

• Elderly patients can commonly present with chronic disease states and resultant compensatory mechanisms • Chronic pulmonary diseases can alter alveolar ventilation and the normal responses to hypoxic and/or hypercarbic conditions.

PERIOPERATIVE RELEVANCE

• CO2 levels can be manipulated under anesthesia, especially with controlled ventilation.

• Central chemoreceptors, located in the medulla, are very sensitive to changes in CSF hydrogen ion concentration. The blood–brain barrier is permeable to dissolved CO2 but not to bicarbonate; therefore acute changes in arterial CO2 content are reflected in the CSF.

Increases in CO2 elevate the CSF hydrogen ion concentration and activate the

chemoreceptors. – This change has an intense initial effect and occurs within seconds; in interstitial fluid, it takes at least 1 minute. This stimulates the respiratory medullary centers to increase alveolar ventilation. Of note, central chemoreceptor activity is depressed by hypoxia. – After several hours, adaptation occurs and the CSF pH normalizes by active transport of bicarbonate ions. – The relationship between arterial CO2 and minute ventilation is nearly linear.

– Peripheral chemoreceptors are located outside the central nervous system; they include the carotid and aortic bodies. The carotid body transmits signals via the glossopharyngeal nerve to the respiratory center in the medulla. Carotid bodies affect ventilation primarily. Removal or denervation, as with carotid endarterectomies, can result in loss of the ventilatory response to arterial hypoxemia and about a 30% decrease in the ventilatory response to CO2. The aortic body transmits signals via the vagus nerve and is primarily

responsible for cardiovascular responses. • Apneic threshold is the highest PaCO2 at which ventilation is zero. Spontaneous respirations

are absent under anesthesia when PaCO2 falls below this value. This is not typically seen in

the awake state due to cortical influences that prevent apnea. Opioids and anesthetic medications significantly depress ventilation by elevating the apneic threshold and hypoxic drive • Apneic oxygenation. When apnea occurs, the alveolar CO2 increases 5–10 mm Hg during the

first minute and 3 mm Hg/minute thereafter. The first minute increase is due to equilibration of the alveolar gas with pulmonary capillary blood. After that first minute, metabolic production is responsible for the steady rise. In practice, the end tidal CO2 monitor is utilized to assess and approximate alveolar CO2.

• Body temperature can directly affect the measurements of the partial pressures of a gas. During hypothermia, both PaCO2 and PaO2 decrease because gas solubility is inversely

proportional to temperature (cold temperatures lead to a decrease in the partial pressure of a gas in the solution). pH, on the other hand, increases because the bicarbonate ion remains unchanged. However, transport of CO2 is not affected by body temperature.

• Hypermetabolism should be considered in a persistently hyperthermic patient in the intraoperative and immediate postoperative period. Hypermetabolic states increase CO2 production and increase sympathetic activation. If not corrected, metabolic acidosis, electrolyte imbalance, and muscle breakdown occur. The differential diagnosis should include malignant hyperthermia, neuroleptic syndrome, thyroid storm, pheochromocytoma, and serotonin syndrome. The end-tidal CO2 can double or triple in value. It is one of the

earliest and most sensitive indicators of malignant hyperthermia. • Administration of acetazolamide, a carbonic anhydrase inhibitor, can impair CO2 transport between tissues and alveoli.

EQUATIONS

H2O + CO2 H2CO3 H+ + HCO3−

REFERENCES

1. Carlson BE, Anderson JC, Raymond GM, et al. Modeling oxygen and carbon dioxide transport and exchange using a closed loop circulatory system. Adv Exp Med Biol. 2006;614:353–360. 2. Andreassen S, Rees SE. Mathematical models of oxygen and carbon dioxide storage and transport: Interstitial fluid and tissue stores and whole-body transport. Crit Rev Biomed Eng. 2005;33(3):265–298. 3. Duffin J. Role of acid-base balance in the chemoreflex control of breathing. J Appl Physiol. 2005;99(6):2255–2265. 4. Smith CA, Rodman JR, Chenuel BJ, et al. Response time and sensitivity of the ventilator response to CO2 in unanesthetized intact dogs: Central v. peripheral chemoreceptors. J Appl Physiol. 2006;100(1):13–19.

ADDITIONAL READING

• Boron WF. Acid-base transport by the renal proximal tubule. Jam Soc Nephrol. 2006;17:2368–2382. • Jensen FB. Red blood cell pH, the Bohr effect and other oxygenation-linked phenomena in blood and CO2 transport. Acta Physiol Scand. 2004;182:216–227. See Also (Topic, Algorithm, Electronic Media Element) • Carotid body • Malignant hyperthermia • Buffering systems

CLINICAL PEARLS

CO2 is transported in three forms: • Dissolved in plasma solution • Bound to carbamino compounds • As bicarbonate ion

CARCINOID Lori Gilbert, MD

BASICS DESCRIPTION

• Carcinoid tumors are rare neoplasms of neuroendocrine tissue and are derived from enterochromaffin cells. • Carcinoid syndrome results from the direct release of vasoactive amines and peptides into the systemic circulation, usually from liver metastases associated with midgut carcinoids, or from bronchial or ovarian primary tumors. Patients commonly experience flushing, diarrhea, bronchospasm, and tachycardia. • Carcinoid crisis is a potentially life-threatening complication of metastatic carcinoid.

EPIDEMIOLOGY Prevalence

• Varies with gender, age, and race. • In the US: 2 per 100,000 per year; higher in males with African descent. • Location: GI tract 65%, bronchopulmonary tract 25%, unknown primary 10%; GI tract tumors have increased significantly over the past 25 years. Prevalence

• Most commonly diagnosed in the 5th or 6th decade; average age is 60.9 years. Additional peaks between 15 and 25 years as well as 65 and 75 years. • Female:male is approximately 2:1 under the age of 50; at older ages, there is a male predominance. Morbidity

• Relatively slow growing and patients may go many years without diagnosis; at presentation, 40–60% are asymptomatic. • Disability arises from flushing, diarrhea, and wheezing. • Cardiac involvement in up to 66% of patients; characterized by fibrous plaques that cover the valves of the right heart (tricuspid valve) with eventual right heart failure. Mortality

• Five-year survival rate: 70–80%; improved survival with appendiceal and lung carcinoid tumors due to low metastatic spread. • Carcinoid crisis accounts for 50% of deaths.

ETIOLOGY/RISK FACTORS

• Mostly sporadic • MEN-1 gene (multiple endocrine neoplasia type 1). In a minority of patients,

neuroendocrine tumors of the lungs, thymus, and stomach can be associated with neoplasia of the parathyroid glands, pancreas, anterior pituitary. About 5–10% of gastric carcinoids are associated with Zollinger–Ellison syndrome and the MEN-1 gene. • First-degree relative: Relative risk of 3.6

PHYSIOLOGY/PATHOPHYSIOLOGY

• Carcinoid tumors secrete vasoactive peptides. When the tumor is outside of the portal system, the peptides cannot be metabolized and symptoms manifest. This occurs in approximately 10% of patients. – Serotonin (5-hydroxytryptamine) is the most prominent. – However, other peptides, however, can be produced such as 5-hydroxytryptophan, bradykinins, tachykinins, histamine, substance P, and adrenocorticotropic hormone. – The two most common symptoms are flushing and diarrhea. Other clinical manifestations include wheezing and skin lesions as well as increased fibrous tissue that can cause retroperitoneal fibrosis resulting in urethral obstruction. – GI tract tumors do not commonly present with symptoms because the released peptides must pass through the liver (and are metabolized) prior to entering the systemic circulation. • Serotonin is a monoamine neurotransmitter that is derived from tryptophan. Normally, the majority of serotonin is secreted by enterochromaffin cells in the gut and stored by platelets. Platelets release serotonin when they bind to a clot; it causes vasoconstriction and aids with hemostasis. Serotonin is metabolized to 5-hydroxyindoleacetic acid (5-HIAA) that can be measured. In high doses, serotonin has abnormal growth promoting effects on the myocardium, and causes myocyte proliferation. • Kallikrein is a serine protease enzyme that converts kininogen to lysyl-bradykinin, which is ultimately converted to bradykinin. It also converts plasminogen to plasmin. Kallikrein is believed to be responsible for flushing. • Bradykinin is an endogenous peptide with potent vasodilator activity and can increase vascular permeability; it stimulates endothelial release of prostacyclin and nitric oxide. It also results in contraction of nonvascular smooth muscle (lungs).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The severity of symptoms is an indicator of perioperative morbidity. Assess for overt symptoms of carcinoid syndrome (diarrhea, flushing, wheezing) as well as heart function and hypertension/hypotension related to carcinoid crisis. • Medications should be optimized, circulating volume restored, and electrolytes replaced prior to surgery. Octreotide has a half-life of 60–90 minutes and will typically require perioperative administration. • The release of peptides can be augmented by stress, surgical manipulation, and betaadrenergic agents. The anesthetic plan should focus on the prevention of mediator release and avoidance of triggering factors; as well as preparation for the management of perioperative carcinoid crisis.

PREOPERATIVE ASSESSMENT

SYMPTOMS

• Diarrhea, flushing, shortness of breath, wheezing, palpitations • Reduced exercise tolerance, orthopnea, paroxysmal dyspnea, peripheral edema may suggest signs of heart failure. History

• Age of onset • Triggers such as stress, alcohol, exercise, certain foods such as cheese, or agents such as catecholamines and serotonin reuptake inhibitors Signs/Physical Exam

• Tachycardia, flushing, lacrimation, wheezing, facial edema, regurgitant murmur • Dehydration • Hypotension • Arrhythmias

TREATMENT HISTORY

• Chemotherapy • Embolization • Hospitalizations or intensive care unit (ICU) admissions • Surgeries; gastric carcinoids can cause intestinal obstruction

MEDICATIONS

• Octreotide mimics natural somatostatin and decreases the secretion of serotonin (as well as gastrin, vasoactive intestinal peptide). It is a potent inhibitor of GH, insulin, and glucagon secretion and is useful in treating flushing and diarrhea. Available in SQ and IV formulations. • Interferon alpha is believed to exert pleiotropic effects (antiproliferation, impair hormone synthesis, alter the major histocompatibility complex, and increase expression of class I antigens on the tumor cells) • Methyldopa inhibits aromatic amino acid decarboxylation (serotonin synthesis) • Ondansetron is an antiserotonergic agent • Nicotinamide treats low levels of tryptophan and pellagra • Diuretics and heart failure medications • Aprotinin is a kallikrein inhibitor

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Chemistry panel (may show effects of chronic diarrhea on electrolytes) • Liver function tests (LFTs) • CBC • Urinary 5-HIAA can indicate progression of carcinoid heart disease • EKG (may show right ventricular hypertrophy) • Chest x-ray

• Echocardiogram to assess for right heart and tricuspid valve disease • Cardiac stress test

CONCOMITANT ORGAN DYSFUNCTION

• Carcinoid heart disease is a late complication, and can occur in 20–70% of patients. The characteristic lesion consists of fibrous plaques covering normal endothelium of the chambers and valves of the right heart (tricuspid valve) • Bronchial involvement • Dermatologic manifestations (pellagra-like lesions) • Skeletal metastases in 10% of patients

CIRCUMSTANCES TO DELAY/CONDITIONS

• Carcinoid crisis. Diarrhea can lead to dehydration, hypotension, and arrhythmias along with unconsciousness; it is potentially life-threatening • Electrolyte abnormalities • Active bronchospasm

CLASSIFICATIONS

• Nonsecretory carcinoid is asymptomatic • Secretory carcinoid (vasopeptides) is symptomatic

TREATMENT PREOPERATIVE PREPARATION Premedications

• Avoid histamine-releasing premedications • Ondansetron has antiserotonin properties • Octreotide 150–250 mcg q6–8 hours for 24–48 hours prior to the surgery. Alternatively, an infusion at 50 mcg/hour for at least 12 hours immediately before surgery • Hydration should be started prior to surgery

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia. Intubation allows control of the airway and the ability to provide positive pressure ventilation • Epidural catheter placement may be considered depending on the type of surgery and volume status of the patient. It should be cautiously bolused and dosed, as patients can have extreme variability in BP Monitors

• Large bore IV access • Fluid warmers • Invasive monitoring (arterial line, central line, pulmonary artery catheter) can aid with monitoring and diagnosis of a carcinoid crisis

Induction/Airway Management

• Laryngoscopy and intubation can trigger the release of carcinoid mediators. Airway instrumentation should not begin until the patient is “deep.” • Opioids such as fentanyl or remifentanil can blunt noxious and pressor responses associated with intubation. • Lidocaine to the vocal cords can help blunt reflexes. • Avoid succinylcholine, mivacurium, atracurium, or thiopental; they can provoke histamine or other mediator release.

Maintenance

• Octreotide should be continued throughout the procedure; it has a half-life of 90–120 minutes • Patients should be kept at a “deep” level of anesthesia to prevent surgical stimulation from releasing peptides • Hemodynamics – Hypotension: Avoid vasoconstrictors such as norepinephrine and epinephrine as they can release substances such as bradykinin and worsen hypotension. IV fluid administration and phenylephrine in small doses are the preferred choices – Hypertension: Labetalol and esmolol deepen the anesthetic • Fluids should be carefully monitored; tumors involving the liver portal system may contribute to large, rapid blood loss • Opioids: Avoid morphine (histamine release); remifentanil and fentanyl are good choices • Carcinoid syndrome intraoperatively is best treated with IV boluses of octreotide 20–50 mcg (titrated to hemodynamics)

Extubation/Emergence

• Consider a deep extubation or extubation while running a low dose of remifentanil to avoid coughing and straining • Observe for signs of bronchospasm and flushing • Have drugs available for BP control

FOLLOW-UP BED ACUITY

ICU setting for IV octreotide, invasive monitoring, fluid management, and analgesia, particularly in patients with a history of carcinoid syndrome or crisis MEDICATIONS/LAB STUDIES/CONSULTS

• Octreotide IV, followed by subcutaneous • Fluid management • Cardiac studies dictated by hemodynamics • Electrolytes/LFTs

COMPLICATIONS

• Complications of octreotide: GI tract pain, nausea, diarrhea, gallstone formation, steatorrhea • Inadequate resection may manifest as carcinoid crisis

REFERENCES

1. Zuetenhorst JM, Taal BG. Metastatic carcinoid tumors: A clinical review. The Oncologist. 2005; 10:123–131.

2. Powell B, Mukhtar AA, Mills G. Carcinoid: The disease and its implications for anaesthesia. Contin Educ Anaesth Crit Care Pain. 2011;11(1):9–13.

3. Maggard M, O’connell JB, Ko C. Updated population-base review of carcinoid tumors. Ann Surg. 2004;240(1):117–122. 4. Schnirer I, Yao J, Ajani J. Carcinoid—A comprehensive review. Acta Oncologica. 2003; 42(7):672–692. 5. Farling PA, Durairaju AK. Remifentanil and anaesthesia for carcinoid syndrome. Br J Anaesth. 2004;92:893–895.

ADDITIONAL READING

• www.carcinoid.org (The Carcinoid Cancer Foundation)

See Also (Topic, Algorithm, Electronic Media Element)

• Epidural • Pheochromocytoma

CODES ICD9 • 209.20 Malignant carcinoid tumor of unknown primary site • 209.60 Benign carcinoid tumor of unknown primary site • 259.2 Carcinoid syndrome ICD10 • C7A.00 Malignant carcinoid tumor of unspecified site • D3A.00 Benign carcinoid tumor of unspecified site • E34.0 Carcinoid syndrome

CLINICAL PEARLS

• Carcinoid crisis may be provoked by stress, chemotherapy, certain foods such as cheese and alcohol, and anesthetic administration. Prophylactic measures should always be taken before anesthesia and surgery such as octreotide and hydration. • Carcinoid syndrome is very rare in patients with pulmonary carcinoids but very common in patients with GI tumor or with liver metastases

CARDIAC ACTION POTENTIAL Jacques Prince Neelankavil, MD Aman Mahajan, MD, PhD

BASICS DESCRIPTION

• The heart consists of pacemaker and myocyte cells that undergo depolarization in order to produce their function. However, their action potentials (APs) are markedly different in regard to how they are initiated, the types of ion channels that are involved, and their repolarization. • Myocytes are responsible for the contractile/mechanical function of the heart. Their APs are not spontaneous; instead they result when adjacent cells (pacemaker and myocytes) are depolarized, similar to dominos. Their AP duration varies depending on the type of myocyte: atrial potentials are ∼150 ms in duration; ventricular potentials are ∼400 ms; and Purkinje potentials are ∼450 ms. Each AP consists of 5 phases (in order of occurrence): – Phase 4: resting membrane potential – Phase 0: rapid depolarization – Phase 1: early repolarization – Phase 2: plateau – Phase 3: repolarization • Pacemaker cells are responsible for initiating the myocyte contraction and depolarize spontaneously; they are found in the sinoatrial (SA) node, interatrial tracts, atrioventricular (AV) node, Bundle of His, Purkinje fibers, and other abnormal sites. Their AP consists of 3 phases: – Phase 4: slow spontaneous depolarization (pacemaker potential) – Phase 0: faster depolarization phase – Phase 3: repolarization – There is no well-defined Phase 1 or 2. PHYSIOLOGY PRINCIPLES

• The membrane potential is regulated by voltage-gated ion channels and pumps within the cell membrane that maintain transmembrane concentration gradients. • Myocytes – Phase 4. The intracellular resting potential of the ventricular cardiomyocyte is between −80 mV and −90 mV. It is created and maintained due to the cell membrane’s high permeability to potassium, while sodium and calcium channels are mostly closed. The high intracellular potassium concentration allows diffusion out of the cell along the concentration gradient. Loss of net positive charge during this phase creates a more negative membrane potential. Extracellular sodium ion concentration is high. The sodium–potassium adenosine triphosphate (ATP) pump prevents complete equilibration of potassium and sodium

across the cell membrane. This ATP-dependent process drives extracellular transport of three sodium ions and intracellular transport of two potassium ions (2 K+ out, 3 Na+ in). Intracellular calcium concentrations are regulated by a sodium–calcium exchanger that maintains a low intracellular calcium concentration. It expels one calcium ion for every three sodium ions that diffuse down its concentration gradient. – Phase 0 marks cell membrane depolarization. At a threshold of −60 mV, fast sodium channels open and sodium ions rapidly move down their electrochemical gradient into the myocyte. The cell depolarizes to +20 mV to +30 mV. Fast sodium channels have activation and inactivation gates. At resting potential, the activation gate is closed and the inactivation gate is open. Upon depolarization, the activation gates open rapidly and the inactivation gates close more slowly. Sodium ions may only enter the cell while both gates are open. A positive feedback loop is created that opens more fast sodium channels and leads to the membrane being depolarized to a positive value. Phase 0 ends as the inactivation gates close. Fast sodium channels activate quickly (<1 ms) in the vast majority of depolarizations. – Phase 1 is the inactivation of fast sodium channels. During this phase, there is a small decrease in membrane potential (early repolarization). Chloride permeability increases and chloride ions move into the cell. Simultaneously, there is a transient efflux of potassium ions. These two ion currents lead to early repolarization. – Phase 2 is the plateau period and its duration is the primary determinant for the length of AP. The plateau portion of the AP is unique to cardiac myocytes. An inward current of calcium ions prevents the cell from repolarizing. The long shoulder of the AP is where calcium enters the cell and facilitates mechanical contraction. There are 2 types of voltage-gated calcium channels in the heart: iCa(T), or transient calcium channels, and iCaL, or long-lasting channels. iCaT have rapid kinetics, whereas

iCaL have slower kinetics because they open more slowly at higher membrane potentials and remain open longer. iCaL are found in all cardiac cells, while iCaT are found mainly

in pacemaker and Purkinje cells. During the plateau, slow delayed-rectifier potassium channels allow outward movement of potassium ions, which balance the inward calcium current. – Phase 3 marks repolarization, leading to the closure of the remaining calcium channels. As the calcium channels inactivate, the slow delayed-rectifier potassium ions remain open, making the membrane potential more negative. Potassium permeability increases secondary to rapid delayed-rectifier (voltage-dependent) potassium channels (iK). The membrane then repolarizes to resting potential at 1/1000th the rate of depolarization. During repolarization, the fast sodium channels convert from inactive to closed. This prepares the channel for the next AP. The absolute refractory period is when the muscle fiber cannot produce another AP due to the inactivation of the fast sodium channels. This period starts during rapid depolarization and lasts until approximately midway through repolarization. The period from the midpoint of repolarization to full repolarization is the relative

refractory period. A larger than normal electrical signal may result in an AP. Inactivation is the basis for refractoriness in cardiac muscle, and is important for prevention of reexcitation. The duration of the ventricular AP is reflected in the QT interval. The QT interval in men and women are equal in childhood; at puberty the QT interval shortens in men. • Pacemaker cells – Phase 4 spontaneous depolarization (pacemaker potential) triggers the AP once the membrane potential reaches threshold between −40 and −30 mV. Unlike the fast sodium channels in myocytes, Phase 4 depends on slow If sodium channels (called funny currents) and calcium channels for depolarization. There is no stable resting membrane potential due to the repeated spontaneous depolarizations. – Phase 0 is the depolarization phase of the AP. – Phase 3 marks repolarization. Once the cell is completely repolarized (about −60 mV), the cycle is spontaneously repeated.

ANATOMY

• The sarcolemma is a specialized lipid bilayer within the myocyte that contains a plasma and basement membrane; it forms the intercalated disks and the transverse tubules (T tubules) as well as contains the pumps and channels responsible for calcium storage and the AP. The intercalated disks allow for rapid conduction of the AP; the T tubules bring the iCaL close to the sarcoplasmic reticulum; and the internal stores of calcium are responsible for converting the AP into a myocardial contraction. • Mitochondria make up ∼40% of the cell’s volume; this is a function of the large amount of ATP required by the myocyte.

DISEASE/PATHOPHYSIOLOGY

• Ischemia. There are ATP-sensitive potassium channels that change shape depending on the metabolic state of the cell. During ischemia, the change in the ADP:ATP ratio activates these channels, and shortens the AP, leading to less force generation, which may be cardioprotective. With worsening ischemia and depletion of ATP, the energy-consuming ion channels can no longer maintain the necessary resting potentials and repolarize the cell. This can precipitate fatal arrhythmias. • Prolonged QT interval can result from defects in ion channels that place the myocardium at risk for fatal arrhythmias. – Abnormality of the delayed-rectifier potassium channels (responsible for repolarization) can cause a long QT interval. – Sodium channels may have defects in inactivation that lead to persistent sodium current. This can lead to long QT syndrome. • Brugada syndrome may result from sodium channel mutations in 20% of patients. • Dilated cardiomyopathy may result from defects in sodium channels via an unknown mechanism. • Mutations in the genes for potassium channels are the primary cause of arrhythmias that result from abnormal repolarization. Gain of function of inward-rectifier potassium channels causes marked acceleration of repolarization and short QT syndrome.

PERIOPERATIVE RELEVANCE

• Adrenergic receptor agonists such as epinephrine can lead to increased calcium current. The increase in intracellular calcium results in stronger contractions by increasing cross-bridge formation. • The sodium–potassium ATPase pump that helps maintain the resting membrane potential is the site of digitalis binding. • Antiarrhythmic medications primarily exert their effects on ion channels and receptors located on the myocyte membrane. The Vaughan Williams system is the most common classification system for these medications. – Class I medications primarily block fast sodium channels. – Class IA medications (quinidine, procainamide, disopyramide) prolong the repolarization and refractory period as well as blocking fast sodium channels. This may lengthen the QRS and QT interval. – Class IB medications (lidocaine, tocainide, mexiletine) have minimal effect on the QRS and QT interval, and they are the weakest of class I medications for blocking sodium channels. – Class IC medications (flecainide, propafenone) increase the QRS interval more than other class I medications, and they are the most potent sodium channel blockers. – Class II medications (propranolol) are beta-adrenergic antagonists. They slow the SA and AV node without an appreciable change in the QT or QRS interval. – Class III medications (sotalol, amiodarone) affect the potassium current and lengthen repolarization and the refractory period. – Class IV medications (verapamil, diltiazem) are calcium channel blockers, which prolong the PR interval. There is no appreciable change in the QRS or QT interval. • The Vaughan Williams classification is useful, but many antiarrhythmic drugs have complex mechanisms of action. – Quinidine has class I and class III effects. – Sotalol has class II and III effects. – Amiodarone has a mechanism of action that involves all 4 classes. – Approximately 50% of patients with ICDs receive antiarrhythmic medications. – Class IC medications affect pacemaker thresholds. – Many antiarrhythmic medications increase defibrillation thresholds. – The biotransformation of most antiarrhythmic drugs occurs in the liver. Amiodarone, propafenone and verapamil are almost exclusively hepatically metabolized. Procainamide, bretylium, and sotalol have minimal hepatic metabolism.

GRAPHS/FIGURES

FIGURE 1. Action Potential of a Ventricular Myocyte. ERP—Effective Refractory Period.

FIGURE 2. Action Potential of a Spontaneously Depolarizing Nodal Myocyte. iCa —Transient Calcium Channels. iCa — (T)

(L)

Long-Lasting Calcium Channels, If Channels (funny current). iK —Rapid Delayed-Rectifier (Voltage-Dependent) Potassium Channels.

REFERENCES

1. Grant A. Cardiac ion channels. Circ Arrhythm Electrophysiol. 2009;2:185–194.

2. Kowey PR. Pharmacological effects of antiarrhythmic drugs. Review and update. Arch Intern Med. 1998;158(4):325–332. 3. Walker CA, Sinale F. The structure and function of the cardiac myocyte: A review of fundamental concepts. J Thorac Cardiovasc Surg. 1999;118:375–382. 4. Zaza A. Control of the cardiac action potential: The role of repolarization dynamics. J Mol Cell Cardiol. 2010;48:106–111. 5. Whalley DW, Wendt DJ, Grant AO. Basic concepts in cellular cardiac electrophysiology. Pacing Clin Electrophysiol. 1995;18(8):1556–1574.

ADDITIONAL READING

• Zipes DP, Jalife J. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia, PA: Saunders/Elsevier; 2009.

See Also (Topic, Algorithm, Electronic Media Element)

• Ventricular tachycardia • Atrial fibrillation • QT prolongation • Premature ventricular contractions

CLINICAL PEARLS

• Abnormalities of cardiac AP may lead to different cardiac arrhythmias. • Different classes of antiarrhythmic medications exert their effect by modifying the different phases of cardiac AP. However, most of the drugs do not have totally isolated effects on different phases of the AP. • There are classes of potassium channels that are activated by acetylcholine, which decreases the slope of depolarization in pacemaker cells and are part of the mechanism of the vagal control of the heart.

CARDIAC CATHETERIZATION Wanda M. Popescu, MD

BASICS DESCRIPTION General

• Left heart catheterization is performed to diagnose and treat coronary artery conditions. It allows real-time visualization of the coronary arterial circulation via injection of contrast under fluoroscopic guidance. Indications include the following (1): – Diagnostic procedures: Confirm and assess the severity of suspected heart disease (chambers and circulation) after a failed stress test. – Therapeutic procedures: Percutaneous coronary interventions (PCI); valvuloplasties and percutaneous valve insertions; septostomy and septal reduction; myocardial biopsy. • Diagnostic uses: Vascular sheaths are introduced, typically into the femoral arteries, and function as a conduit by which other instruments are then inserted. – Coronary angiography is performed by advancing a balloon-tipped catheter into the aorta and through the coronary ostia to access the coronary circulation; dye is injected to delineate the anatomy, collaterals, and blockages. – Ventriculogram is performed by subsequently pulling the catheter back into the ascending aorta and advancing it through the aortic valve (AV); dye is injected into the left ventricle (LV) to assess its function. – Pressures in chambers and gradients across valves are also measured. • Therapeutic uses – Percutaneous transluminal coronary angioplasty (PTCA) consists of inflating a balloon at the level of the narrowed coronary artery to improve blood flow. – Stenting consists of deployment of mesh-like structures that are loaded onto angioplasty balloons. They fixate to the coronary wall via hooks and prevent acute recoil. Bare metal stents (BMS), introduced in the 1990s, are metallic mesh-like structures. Drug-eluting stents (DES), FDA approved in 2003, are similar to BMS but release a medication designed to inhibit restenosis. – The presence of a raw surface on the coronary artery (stent) mandates preprocedure loading with dual antiplatelet therapy (DAPT) and treatment continuation until stent endothelialization is complete; BMS require ~2 months, whereas DES require 1 year or more. – Valvuloplasties are performed to dilate stenotic valves (aortic, mitral) by inflating a balloon at the level of the valve. More recently, aortic valves have been successfully inserted percutaneously. – Septal reductions are performed in patients with hypertrophic obstructive cardiomyopathies. During cardiac catheterization, alcohol is injected in the septal perforator artery that supplies the area of hypertrophied interventricular septum (induces

necrosis of the area and thus reduces outflow tract obstruction). – Septostomies are performed in patients with congenital heart disease requiring a right-toleft shunt. A balloon-tipped catheter is inserted percutaneously into the venous system and advanced via the right atrium into the fossa ovalis, which is dilated by balloon inflation. • Right heart cardiac catheterization allows for measurement of right heart and pulmonary circulation pressures as well as oxygen saturation via blood sampling (not addressed here). • Advantages of PCI over coronary artery bypass surgery (CABG) include the following: – Less invasive treatment of coronary artery disease (CAD) – Decreased impact on major organ function – Decreased intensive care unit (ICU) or hospital stay – Faster recovery to full activity, reduced postoperative pain – Outcome studies in patients with 3-vessel or left main disease show similar rates of major adverse cardiac events or cerebrovascular events at 1 or 2 years when comparing PCI with DES versus CABG (2,3,4) • Disadvantages of PCI over CABG – Prolonged treatment with DAPT and increased risk of spontaneous or surgical bleeding – May require repeat target lesion revascularization – No long-term survival benefit

Position Supine

Incision

• Femoral artery puncture • Other possible puncture sites: Axillary, brachial, or radial artery

Approximate Time 1–2 hours

Expected Blood Loss

• Usually minimal • Potential for significant blood loss with major vessel or cardiac injury

Hospital Stay

• In elective cases, may be discharged home the same day • In acute coronary syndrome (ACS) situations, 2–3 days, possibly longer • In cardiogenic shock, prolonged ICU stays may be necessary

Special Equipment for Surgery

• Cardiac catheterization laboratory • Fluoroscopy machine, IV contrast dye injector, intravascular ultrasound • Ideally: Cardiac operating room available within the same building

EPIDEMIOLOGY Prevalence

• 1 million PCI/year in the US • During PCI, 90% of patients receive at least 1 stent

Morbidity

• Coronary artery restenosis manifests as reoccurrence of anginal symptoms – PTCA: 30–40% – BMS: 20–30% – DES: <10% • Late stent thrombosis manifests as death or myocardial infarction – BMS rare – DES 0.5–3.1%, possibly higher Mortality

• At the time of PCI: 1% • Acute vessel recoil post-PTCA: 20% • Late stent thrombosis: 45–75%

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Anesthetic care is usually requested for patients with significant comorbidities or hemodynamic instability. • Anticoagulation requirements: High-dose loading with antiplatelet drugs pre-PCI, IV antiplatelet therapy, as well as systemic anticoagulation during and post-PCI (5). • Preoperative PCI may increase the risk of major adverse cardiac events at the time of surgery. Perioperatively, the risk of surgical bleeding incurred by maintaining DAPT should be balanced against the risk of stent thrombosis and possible death encountered when aspirin and clopidogrel are discontinued prematurely. • Out-of-OR case. Anesthesia machine and cart, as well as availability of suction are mandatory. Establish communication with the OR floor manager and anesthesia technician such that, in case of an emergency, help is easily available.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Elective: Asymptomatic, exercise-induced or atypical angina • Emergency: Unstable angina or ACS ± cardiogenic shock

History

• Often identified as a failed stress test • Associated comorbidities: Hypertension, heart failure, arrhythmias, diabetes, peripheral vascular disease, smoking history, chronic obstructive pulmonary disease (COPD), chronic kidney injury

Signs/Physical Exam

S3, S4 heart sounds and bibasilar crackles in patients with heart failure

MEDICATIONS

• Beta-blockers are beneficial by decreasing heart rate, vascular shear stress, and by attenuating the sympathetic output and thereby decreases platelet reactivity. • ACE-inhibitors and angiotensin receptor blockers (ARBs) decrease afterload and revert LV remodeling • Diuretics decrease preload • DAPT prevents acute stent thrombosis. • Statins have pleiotropic effects (lipid lowering, coronary plaque stabilization).

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hematocrit/hemoglobin, potassium, creatinine, coagulation profile; platelet function assay (if available) • Echocardiography results (if available) • Stress test results (if available)

TREATMENT PREOPERATIVE PREPARATION Premedications

• Loading with high-dose clopidogrel (300–600 mg) and aspirin (PO or orogastric tube/nasogastric tube) • Anxiolysis as appropriate

Special Concerns for Informed Consent

• Low ejection fraction (EF) or high-grade left main disease patients may require pre-PCI placement of intra-aortic balloon pump (IABP) • Cardiogenic shock patients may require pre-PCI placement of a percutaneous LV assist device (pVAD) like the Impella® or TandemHeart® • Potential for conversion to open heart surgery • Consent for possible blood transfusions

INTRAOPERATIVE CARE Choice of Anesthesia

• Most cases are performed without anesthesia care under mild/moderate sedation administered by a cath lab nurse (6). • Situations where anesthesia services are required include patients that are critically ill, hemodynamically unstable, morbidly obese with significant sleep apnea, cannot lie flat, claustrophobic, or mentally impaired. General anesthesia (usually with endotracheal tube [ETT]) is often performed. Monitors

• Standard ASA monitors

• Arterial waveform can be derived from the groin access lines placed by the cardiologist. • Good IV access for rapid resuscitation in case of vascular damage or emergency cardiac surgery • Foley catheter • Transesophageal echocardiography/transthoracic echocardiography (TEE/TTE) is useful to assess cardiac function, detect complications, and guide management.

Induction/Airway Management

• Controlled induction to avoid hemodynamic instability • Emergency airway tools readily available (LMA, indirect video laryngoscopy)

Maintenance

• Volatile or IV agents can be used for maintenance of anesthesia. Volatile agents offer the theoretical advantage of ischemic preconditioning of the myocardium. There is no data to suggest that decreases in myocardial contractility seen with volatile or IV anesthetics impact overall patient outcome. • Anticoagulation – Systemic heparinization is administered to a desired activated clotting time (ACT) of 300– 350 seconds. For patients with heparin-induced thrombocytopenia, direct thrombin inhibitors, factor Xa inhibitors, or defibrinogenating agents are used. No test is available to monitor the effect of these agents. Patients may be overdosed (manifests as generalized bleeding). – IV antiplatelet drugs (glycoprotein IIb/IIIa inhibitors) may be required. • Significant hypotension suggests cardiogenic shock or hypovolemic shock due to massive hemorrhage (cardiac or vascular injury).

Extubation/Emergence

• Standard extubation criteria; consider postoperative intubation if the patient is hemodynamically unstable. • Control BP and heart rate during emergence with IV agents such as beta-blockers, nitroglycerin, diltiazem, and clevidipine. • Neurologic exam (potential for cerebral embolic event)

FOLLOW-UP BED ACUITY

• Elective, noncomplicated case: Discharged home or admitted to regular floor overnight • Technically difficult case or hemodynamically unstable: Telemetry or cardiac care unit (CCU) • Antiplatelet medications will need to be continued post-PCI • Avoid groin flexion

ANALGESIA

Usually minimal pain, controlled with acetaminophen or PO opioids

COMPLICATIONS

• Acute vessel recoil post-PTCA • Stent thrombosis – Early (within 1 month of PCI): Usually represents a technical error – Late (after 1 month): Usually when DAPT is prematurely stopped. • Major vessel or coronary artery injury (dissection, laceration) • Cardiac perforation with pericardial tamponade and shock • Embolization of atheromatous debris (stroke, abdominal organ ischemia) • Major bleeding (from aggressive anticoagulation and antiplatelet therapy) • Access site hematoma, pseudoaneurysm formation, or infection • Contrast-induced acute kidney injury

REFERENCES

1. hook DC, Gross W. Offsite anesthesiology in the cardiac catheterization lab. Curr Opin Anesthesiol. 2007;20:352–358. 2. Bravata DM, Gienger AL, McDonald KM, et al. Systematic review: The comparative effectiveness of percutaneous coronary interventions and coronary artery bypass graft surgery. Ann Intern Med. 2007;147:703–716. 3. Serryus PW, Morice M-C, Kappetein AP, et al. Percutaneous coronary interventions versus coronary artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360:961–972. 4. Park S-J, Kim Y-H, Park D-W, et al. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med. 2011;364(18):1718–1727. 5. evine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Interventions. http://content.onlinejacc.org/cgi/content/full/j.jacc.2011.08.007v1 6. Braithwaite S, Kluin J, Buhre WF, et al. Anesthesia in the cardiac catheterization laboratory. Curr Opin Anethsiol. 2010;23:507–512. See Also (Topic, Algorithm, Electronic Media Element) • Coronary artery disease • Coronary artery bypass grafting • Radiation safety • Cardiac tamponade

CLINICAL PEARLS

• PCI is a less invasive modality compared to coronary artery bypass for the treatment of CAD when medical therapy is insufficient. • Patient population with multiple comorbidities • Requires systemic anticoagulation and high-dose antiplatelet medications. Thus, patients have an increased risk of spontaneous bleeding. • In cardiogenic shock, IABP or pVAD can be place pre-procedure.

• May require repeat interventions for restenosis or stent thrombosis • 1- and 2-year outcomes of PCI are similar to CABG. There are no long-term survival benefits demonstrated.

CARDIAC OUTPUT Rebecca L. Reeves, DO Nanhi Mitter, MD

BASICS DESCRIPTION

• Circulating blood is necessary for meeting the nutritional demands of tissues, removing wastes, delivering hormones, and keeping an environment in all tissue that is optimal for cell function and survival. • The rate of blood flow to tissue is dependent on its nutritional needs. Cardiac output (CO) is maintained by alterations in the heart and blood vessels. • CO is the amount of blood pumped out of the heart into the aorta each minute; it is blood flow. – Average CO for adults: 5.6 L/minute for males, 4.9 L/minute for females. – Varies with age, physical activity, body surface area (BSA), and metabolism. – Cardiac index (CI). Because CO increases proportionally with BSA, CI can be used as a measurement. Average CI is approximately 3 L/min/m2. PHYSIOLOGY PRINCIPLES

• Extrinsic factors that control CO: – The Frank–Starling law is the heart’s built-in mechanism to control CO. It states that increased venous return (end diastolic volume; EDV) increases wall stretch of the heart chambers and myocardial cells; this allows cardiac muscle to have greater contractile force resulting in an increase in SV and therefore CO (Figure 1). An analogy is a bow and arrow; the greater the stretch, the greater the force exerted on the arrow. However, past a certain EDV, further filling can become ineffective (will exceed troponin and myosin overlap and result in a decrease in contractile force and decrease in CO).

FIGURE 1. Effects of changes in afterload on Frank-Starling curves. A shift from A to B occurs with increased afterload, and from A to C with decreased afterload. From Richard Klabunde. www.cyphysiology.com, 2011, with permission.

– Stretch of the sinus node in the wall of the right atrium (RA) has a direct effect on heart rate (HR), increasing HR by as much as 10–15%. – The Bainbridge reflex is a nervous system reflex, also initiated by a stretched RA, that increases HR. – In translation, the heart, itself, is not principally responsible for CO. Under normal, unstressful situations, CO is controlled by extrinsic factors, mainly venous return. • Intrinsic factors that control CO: – HR depends on the diastolic interval. The diastolic interval is controlled by the sinoatrial (SA) node pacemaker (dependent on calcium and potassium channels). – EDV depends on filling pressure, filling time, and ventricular compliance. Longer filling times → increases EDV. Increased ventricular compliance → increased EDV. • End systolic volume (ESV) depends on – HR: Increased HR is secondary to increased calcium in pacemaker/myocardial cells; this also results in increased contractility, and decreased ESV. – Contractility: Increased inotropy will result from increases in calcium within myocardial cells, with resultant increases in contractility and HR and decreases in ESV. – Preload: Increased EDV increases stretch and consequently contractile forces, with a resultant decrease in ESV. – Afterload: Increases prevent the heart from emptying with resultant increases in ESV. • Ejection fraction (EF) is a term that is utilized to describe the systolic function of the heart in terms of SV and EDV. It is the percentage of blood that is ejected by the ventricles with heart beat; normal is ∼55–65%.

ANATOMY

• Arteries: High pressure, high flow, strong vascular walls. Function: Transport of blood to tissues. • Arterioles: Small branches of arteries, variable flow and pressure. Function: Control conduits; muscular walls are able to contract and dilate to vary local blood flow in tissue beds. • Capillaries: Small thin-walled vessels. Function: Nutrient/waste exchange site. • Venules: Collect blood from capillaries and form progressively larger veins. • Veins: Low volume, thin walls, low pressure. Function: Return blood back to the heart, serves as a reservoir of blood, can also contract/dilate depending on circulatory needs. • SA node: Located at the junction of the SVC and RA. Serves as the cardiac pacemaker, largely dependent on calcium channels. • Cardiac myocytes: Striated muscle with gap junctions that allow muscle fibers to function as a unit. • Distribution of CO to organs: Brain 15%, heart 5%, kidneys 20%, liver 25%, muscle 15% (can increase to up to 65% with exercise), skin 10%, bones/fat/ other 15%.

DISEASE/PATHOPHYSIOLOGY

• High CO states (usually as a result of decreased SVR or shunts): Activates the reninangiotensin system and increases sympathetic output with resultant increases in heart rate, vasoconstriction, and salt and water retention. Leads to ventricular remodeling and failure.

– Beri beri: Thiamine deficiency that leads to peripheral vasodilation, increased CO, salt retention, and edema. Because of a high CO, the myocardium sustains overuse injuries that can lead to tachycardia, edema, high pressures, and chest pain. – AV shunt (fistula): Reduces SVR and arterial BP; this is compensated by increasing the CO. – Hyperthyroid: Increased metabolism results in decreased SVR that is compensated by increasing the CO. – Anemia: Decreases blood viscosity and SVR along with vasodilation from increased nitric oxide synthase. – Obesity: Increases blood volume and CO to sustain excess body mass. – Cirrhosis: Results in splanchnic vasodilation, and also development of shunts. – Pregnancy: Increased metabolic demand is compensated for with an increase in the circulating blood volume and HR. – Shock: The release of cytokines results in extreme vasodilation and decreased SVR; this is compensated for by an increase in CO. • Low CO states: – Hypovolemia: Decreased venous return and EDV result in decreased CO – Acute venous dilatation: similar to hypovolemia, with decreased EDV. – Obstruction of large veins: Again, decreased venous return leading to a decrease in the EDV – Arrhythmias: Decreased ventricular filling time and decreased SV lead to decreased CO. – Decreased metabolic rate – Late sepsis: Inadequate tissue oxygenation leads to multiorgan failure, including heart failure. – Regional wall motion abnormalities due to ischemia: Decreased contractility resulting in decreased EF. – Valvular disease: Leads to structural changes in the heart muscle and eventual decreases in systolic function (EF). – Cardiomyopathy: Impaired ventricular compliance resulting in decreased contractility via Frank–Starling law.

PERIOPERATIVE RELEVANCE

• Mean arterial pressure (MAP) is the perfusion pressure to organs. MAP = CO × SVR. • As preoperative clinicians, we need to understand the interrelationship of these physiologic parameters in order to intervene appropriately, as too high or too low CO can be detrimental to the patient. • Measuring CO. In the perioperative setting, this is typically done via invasive monitoring. Furthermore, CO measurements do not provide information about end-organ blood flow and oxygen utilization by tissue. Currently, the only monitor that addresses this is mixed venous oxygen saturation (SvO2).

– Thermodilution technique via the Swan–Ganz catheter is frequently used. – Echocardiography measures changes in the ventricular volumes to calculate stroke volume, which is then multiplied by the HR. – Velocity encoded MRI. Very accurate method to measure velocity based on detection of changes in the phase of proton precession.

– Arterial line waveform analysis. Area under the curve equals work or stroke volume. – Invasive pulse pressure, involves inserting a manometer in the artery, the waveform is analyzed and CO calculated. – SvO2: Blood samples are collected viaa pulmonary artery catheter. Reflects balance of

oxygen delivery, determined by CO, and oxygen consumption. – Receptors β1: Directly increases HR (chronotropy) by stimulating the SA node, and increases contractility (inotropy) and automaticity of cardiac muscle all increase CO. β2: Dilates arteries to skeletal muscle which ↓ afterload and ↑ stroke volume and therefore CO, but to a lesser degree than β1 receptors. α1: Principle effect is vasoconstriction which increases the SVR. Dopamine: Increases HR and BP. Low doses: Vasodilates and increases renal blood flow. Intermediate doses: Increases CO by positive chronotropy and inotropy. High doses: Acts as a pressor causing vasoconstriction. • Drugs and receptors – Epinephrine: Has both β and α activity – Norepinephrine: Predominantly α activity – Dobutamine: β1 selective – Isoproterenol: β1 and β2 – Phosphodiesterase inhibitors: Increases contractility, pulmonary, and systemic vasodilation – Calcium: Directly increases myocardial contractility – Glucagon: Acts as a positive inotrope and increases CO. Also, decreases SVR by arterial and venous vasodilation • Hypotension. Workup should include an assessment of preload, afterload, contractility, HR, and rhythm in light of the clinical picture. The ASA/SCA recommends obtaining transesophageal echocardiography when the diagnostic information will alter the management – this includes unexplained persistent hypotension. • Decreased CO likely results in a longer IV drug circulation time and slower onset of action. Conversely, volatile agents have a quickened onset due to a more quickly increased alveolar concentration (less volatile agent is carried away). Increased CO results in a faster IV drug onset time, while volatile agents have a slower onset (slower increase in alveolar concentrations).

EQUATIONS

• OHM’s law: V = I / R or Flow = Pressure/Resistance • CO = MAP/SVR (PVR for right heart, SVR for left heart) • CO = SV × HR • SV = EDV – ESV • Fick principle: CO = VO2/(CaO2 −CvO2); where VO2 is oxygen consumption, CaO2 is arterial oxygen concentration, and CvO2 is venous oxygen concentration

• CI = CO/BSA – BSA = 0.20247 × height (m)0.725 × weight (kg)0.425

REFERENCES

1. Guyton AC. The relationship of cardiac output and arterial pressure control. Circulation. 1981;64:1079–1088. 2. de Waal EE, Wappler F, Buhre WF. Cardiac output monitoring. Curr Opin Anaesthesiol. 2009;22:71–77.

3. Rothe CF. Physiology of venous return. An unappreciated boost to the heart. Arch Intern Med. 1986;146:977–982. 4. Thys DM, Abel MD, Brooker RF, et al. Practice guidelines for perioperative TEE: An updated report by the American Society of Anesthesiologists (ASA) and the Society of Cardiovascular Anesthesiologists (SCA) Task Force on TEE. Anesthesiology. 2010;112:1084– 1096.

ADDITIONAL READING

• Ejection fraction • Cardiac output methods to measure • High output cardiac failure • Mixed venous oxygen saturation

CLINICAL PEARLS

• Circulatory shock is inadequate tissue perfusion caused by inadequate CO. • Hypovolemic shock → the pump is empty. Administer either crystalloid, colloid, or blood products. • Distributive/vasogenic shock → SVR is low. Give pressors with strong α1 activity: Phenylephrine, norepinephrine, ephedrine • Cardiogenic shock → pump failure. Administer pressors with strong β1 properties, epinephrine, dopamine, etc. until the underlying cause can be fixed. • Obstruction to flow → valvular lesions, pulmonary HTN. Surgical correction, inhaled nitric oxide, and phosphodiesterase inhibitors. • Bradycardia, heart block → ACLS protocols or treat with atropine, glycopyrrolate, cardiac pacing.

CARDIAC OUTPUT METHODS TO MEASURE Amrik Singh, MD

BASICS DESCRIPTION

• Cardiac output (CO) is the volume of blood pumped by the heart per unit time and is measured in liters/minute. In the absence of any intracardiac shunt, both right and left ventricular output are roughly equal. • Continuous CO monitoring provides dynamic information that can facilitate rapid adjustments in therapy. PHYSIOLOGY PRINCIPLES

• Fick’s method. Originally described by Adolph Fick in 1870. – Technique: CO is measured by dividing the body’s oxygen consumption (VO2) by the

difference in arterial and mixed venous blood oxygen content (CaO2–CvO2). CO = VO2/(CaO2–CvO2). O2 content of arterial or venous blood is determined by adding the O2

bound to hemoglobin (Hb) with that dissolved in blood: [Hb × 1.36 × O2 saturation] +

[PaO2 × 0.003].

– Equipment: VO2 can be measured via spirometry or a closed rebreathing circuit. The PaO2 is attained from an arterial blood gas (ideally pulmonary vein) and the PvO2 from the

pulmonary artery. – Pros The original reference standard by which all others are evaluated Good accuracy in low CO states because the arterial to venous O2 content difference is reliably augmented – Cons Technically difficult to attain VO2 values. To that extent, it can be estimated from an individual’s height and weight (Fick’s determination) using a value of 125 mL O2/min/m2.

Fick’s method is not reliable in patients with varying O2 demands, impaired lung gas exchange, and unstable hemodynamics because the O2 content and consumption are

rapidly changing. • Pulmonary artery catheter thermodilution method (PAC TD) – Technique: Based on the modified Steward–Hamilton indicator diffusion equation. A known amount of cold solution at a known temperature is injected at one port and measured at a downstream port; the change in temperature is calculated and extrapolated into a CO measurement. In low CO states, lower blood flow results in greater temperature change (more time to equilibrate with the body’s warmer temperature), whereas in high

CO states, the blood moves more quickly and there is less time for a change in temperature. – Equipment: Heat is used as an indicator instead of lithium or other dyes (e.g., indocyanine green). A known amount of cold solution is injected in the proximal port that lies in the right atrium, and the change in blood temperature is detected by a thermistor at the catheter tip located in the pulmonary artery. – Pros Considered the clinical gold standard due to extensive experience with this technique Allows quick successive measurements No blood sampling is required – Cons Several measurements are needed to calculate an average since the pulmonary blood flow changes during the respiratory cycle Many factors including temperature and volume of the injectate, concomitant rapid intravenous fluid administration, and presence of pulmonic or tricuspid regurgitation can affect the accuracy A right-to-left intracardiac shunt will enable some of the indicator to bypass the thermistor and overestimate the cardiac output A left-to-right intracardiac shunt will result in recirculation of dye resulting in underestimation of the cardiac output There is an inherent 10–20% error in measurement • Pulmonary artery catheter continuous cardiac output (PAC CCO) – Technique: Continuous detection of temperature changes from the proximal to distal port. Utilizes dissipation of heat instead of cold injectate used in the bolus thermodilution method. The CO value is averaged over 4–6 minutes, although a STAT mode is available to display it every sixty seconds. – Equipment: An embedded heat filament that rests between the right atrium and ventricle emits small thermal pulses every 30–60 seconds. – Pros Good correlation with bolus thermodilution method Provides hands-free continuous data – Cons: Prone to error with sudden changes in blood flow or concomitant rapid infusions of cold or warm fluids. • Partial CO2 rebreathing (NiCO2) – Technique: Utilizes the differential Fick’s principle; carbon dioxide elimination is measured in lieu of measuring VO2. CO is based on breath-by-breath measurements of CO2 elimination.

– Equipment: The NiCO2 system is noninvasive and has a built in rebreathing valve and loop. Infrared sensors and flow meters measure and calculate CO2 elimination after a brief

period of partial rebreathing. – Pros: CO2 elimination is easier to measure accurately than O2 due to its high diffusion rate. – Cons

Requires mechanical ventilation Not accurate in the presence of intrapulmonary shunts (however this is present in most critically ill patients) • Transpulmonary thermodilution (TPCO) – Technique: Measures the temperature change in a central artery after injection of cold saline into a central vein. – Equipment: A known amount of cold saline is injected in a central line. After passing through the right heart, pulmonary circulation and left heart, the final temperature change is measured by a thermistor-tipped catheter placed in a central artery (axillary or femoral). – Pros Less invasive than PAC Validity is comparable to more invasive techniques Simultaneous injection of indocyanine green (which stays in the intravascular space) and cold saline (which equilibrates with the extravascular space) can provide measurements of the total thoracic intravascular volume and extravascular fluid volume – Cons Requires invasive intravascular lines Concomitant rapid intravenous fluid administration can affect accuracy • Pulse dye densitometry – Technique: Dye is injected intravenously, and the arterial concentration is measured. Calculation of CO is based on a concentration versus time curve. – Equipment: Indocyanine green dye distributes exclusively in the intravascular space. Noninvasive arterial concentration is measured with a fingertip sensor. The same principle of pulse oximetry is utilized (the ratio of the pulse absorbance signals is obtained at two wavelengths). – Pros: Noninvasive (indirect sampling) – Cons: The accuracy of this technique has not yet been validated. • Doppler ultrasound (esophageal Doppler probe) – Technique: Aortic blood flow is calculated by multiplying blood flow velocity over time with the cross-sectional area of the aorta. – Equipment: An esophageal probe is placed at the level of the descending aorta, approximately 35 cm from the incisors. The probe position is optimized by slow penetration and rotation to obtain a clear Doppler signal and blood flow velocity in the aorta. Aortic diameter is obtained either from a built in nomogram linked to patient demographics or using an M-Mode echo transducer built into the probe. – Pros: The shape of the velocity versus time wave can also be used to estimate preload, afterload, and contractility. – Cons Poorly tolerated in awake, unintubated patients Accuracy is dependent on nonturbulent blood flow, angle of the Doppler beam and aorta, and the relative distribution of blood flow to the upper part of the body • Transesophageal echocardiography (TEE) – Technique: Based on measuring the area and blood flow velocity at a particular location in

the heart. The left ventricular outflow tract (LVOT) is the most commonly used site due to its nearly circular shape. LVOT area is calculated using the mid-esophageal long axis or transgastric long axis view. Velocity time integral (VTI) is obtained by placing pulse wave Doppler sample volume at the same location in the LVOT: Stroke volume = LVOT area × VTI. – Equipment: Echocardiography – Pros Avoids blood distribution assumptions made in the esophageal Doppler method 3D echocardiograms can calculate the CO by direct stroke volume (SV) measurements – Cons Transesophageal echocardiography is invasive; alternatively, the transthoracic approach can be utilized, but the image quality may be suboptimal Technically more demanding and requires special expertise • Pulse contour analysis-based methods – LiDCO system Technique: Based on pulse power analysis, not pulse morphology. The arterial pressure wave is transferred to a volume wave and the net power is calculated (proportional to the net flow/SV). Equipment: External calibration is performed using the lithium dilution method. Isotonic lithium chloride is injected into a peripheral vein and its concentration is measured with an electrode attached to a peripheral arterial line. Pros: Less invasive. Measures CO independent of sampling site. Cons: The external calibration needs to be repeated after significant changes in hemodynamics or arterial compliance. However, the newer LiDCO plus system is capable of self-calibration. – PiCCO system Technique: Based on BP waveform morphology and calculates CO by using an algorithm described by Wesseling and colleagues. Equipment: Peripheral arterial catheterization provides the pressure waveform. It requires external calibration by the transpulmonary thermodilution method as described above. Pros: Less invasive. Accuracy validated in a number of studies. Cons: Frequent recalibration is required in the presence of intravascular volume changes or hemodynamic instability. – FloTrac/Vigileo system Technique: Works on the principle that the pulse pressure is directly proportional to the SV and inversely proportional to aortic compliance. Uses arterial pulse analysis in conjunction with patient’s height, weight, age, and gender. The system recalibrates itself frequently. Equipment: Standard peripheral arterial catheter attached to a special high-fidelity pressure transducer and monitor. Arterial site not important but the quality of pulse tracing is relevant. Pros: No external calibration is required. Derives percent stroke volume variation (SVV) that has been shown to be a reliable indicator of intravascular volume status. Good

correlation with PAC-based thermodilution method. Cons: Unlike PAC, right heart filling pressure and mixed venous O2 saturation level not

provided. • Bioimpedance cardiography – Technique: Based on changes to electrical resistance in the thoracic cavity associated with varying amounts of aortic blood volume during systole and diastole. Higher thoracic blood volume reduces impedance. SV is calculated using a built-in algorithm. – Equipment: Four pairs of electrodes apply high-frequency, low-amplitude alternating current and sense impedance changes related to pulsatile blood flow. – Pros Completely noninvasive Can also measure intrathoracic fluid volume and LV ejetion time – Cons Accuracy is questionable in the setting of significant ambient electrical noise and body motion A new device (NICOM, Cheetah Medical) that uses phase shifts of the received signal relative to the applied signal resulting from blood volume induced bioreactance changes in the thorax, may be less susceptible to external noise

PHYSIOLOGY/PATHOPHYSIOLOGY

– CO is determined by preload, afterload, and contractility; therefore, the etiology of low CO state could be traced to three fundamental causes: – Pump failure from ischemic or nonischemic causes – Hypovolemia – Low systemic vascular resistance (SVR)

PERIOPERATIVE RELEVANCE

• Intraoperative hypotension is a common occurrence. Since MAP = CO X SVR, measuring CO will help in the treatment of persistent hypotension unresponsive to simple empirical treatment. • Knowing CO is also helpful in monitoring the response of inotropic/vasoactive drugs.

EQUATIONS

• Fick’s equation: CO = VO2/(CaO2–CvO2) where VO2 = O2 consumption and (CaO2–CvO2) = arterial and mixed venous oxygen content difference. • CO = VCO2/(CvCO2–CaCO2) where VCO2 = CO2 production and (CvCO2–CaCO2) = venous and arterial CO2 concentration difference.

• VTI = Velocity time integral measured by Doppler ultrasound = stroke distance. • Stroke volume = stroke distance X cross-sectional area at the sampling site.

REFERENCES

1. eyton PJ, Chong SW. Minimally invasive measurement of cardiac output during surgery and critical care: A meta-analysis of accuracy and precision. Anesthesiology.

2010;113(5):1220–1235. 2. Mathews L, Singh RK. Cardiac output monitoring. Ann Card Anaesth. 2008;11:56–68.

3. Pugsley J, Lerner AB. Cardiac output monitoring: Is there a gold standard and how do the newer technologies compare? Semin Cardiothorac Vasc Anesth. 2010;14:274–282. 4. Skowno JJ, Broadhead M. Cardiac output measurement in pediatric anesthesia. Paediatr Anaesth. 2008;18:1019–1028. 5. de Waal EE, Wappler F, Buhre WF. Cardiac output monitoring. Curr Opin Anaesthesiol. 2009;22:71–77. See Also (Topic, Algorithm, Electronic Media Element) • Cardiac output, high • Cardiac output

CLINICAL PEARLS

• Fick’s method, traditionally considered the gold standard by many, is technically challenging. PAC TD has been the practical gold standard in recent decades but the use of PACs is declining. • Arterial pulse contour analysis-based monitors, especially the Flo Trac system, are gaining popularity (reliable and use-friendly). SVV calculation adds additional value to these methods. • Not all methods can be used in the pediatric population. For example, the PAC, TP TD, and esophageal Doppler method have patient size limitations. • Given the variability of measurements with any modality, trends in CO may be more useful than absolute values.

CARDIAC OUTPUT, HIGH Rashmi R. Rathor, MD Ivan M. Kangrga, MD, PhD

BASICS DESCRIPTION

• High cardiac output (HCO) is a hyperdynamic circulatory state marked by low mean arterial blood pressure (MAP) and tachycardia: – Cardiac output (CO) > 8 L/min or cardiac index (CI) > 4 L/min/m2 – Systemic vascular resistance (SVR) <900 dynes × seconds/cm5 or SVR index (SVRI) <1680 dynes × seconds/cm5/m2 EPIDEMIOLOGY Prevalence

HCO in the general population: Unknown Prevalence

• End-stage liver disease (ESLD): Over 400,000 (0.15%) in the US • SIRS/sepsis over 130 per 100,000 persons • Hyperthyroidism: 1.5% in general population, more common in women than men (5:1).

Mortality

• ESLD: About 35,000 deaths per year and the 9th leading cause of death in the US. • Sepsis: In hospital mortality is 30–50%; it is the 10th leading cause of death in the US. • Thyroid storm mortality is 10–20%.

ETIOLOGY/RISK FACTORS

• Physiologic causes: Anxiety, exercise, pregnancy, fever • Common pathologic causes: ESLD, SIRS/sepsis, hyperthyroidism, obesity • Less common pathologic causes: Arteriovenous (AV) fistula, anemia (Hg <7 g/dL), carcinoid, beriberi, hereditary hemorrhagic telangiectasia, dermatologic diseases, Kaposi sarcoma, multiple myeloma, Paget’s disease.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Decreased SVR leading to a low MAP is often the primary circulatory derangement leading to HCO. Two principal causes of low SVR are as follows: – Vasodilated small and precapillary arterioles – AV shunting, including iatrogenic AV fistulas • Compensatory mechanisms are triggered by a low SVR and MAP: – Chronic activation of the sympathetic nervous system (SNS) causes tachycardia and increases plasma catecholamines, vasomotor tone, myocardial contractility, and CO.

– Activated renin-angiotensin-aldosterone system (RAAS) maintains systemic BP by vasoconstriction and sodium retention. – Nonosmotic hypersecretion of arginine vasopressin results in retention of free water in order to preserve the circulatory volume. • Heart failure may occur regardless of the etiology of HCO; it is defined by clinical evidence of heart failure and a CI > 4 L/min/m2 (3)[A]. Chronic SNS activation and an excess of catecholamines cause tachycardia, arrhythmogenesis, β1 receptor down-regulation, increased myocardial oxygen consumption VO2, and tachycardia-mediated dilated

cardiomyopathy. • ESLD: Mesenteric vasodilators (nitric oxide [NO], carbon monoxide, cytokines, etc.) cause splanchnic arterial and venous vasodilatation (1)[A]. – Splanchnic arterial dilatation is so profound that it lowers the overall systemic SVR. – Splanchnic venous dilatation causes pooling of venous blood and functional hypovolemia. – A dual circulation exists with a (1)[A]: Primary derangement causing a low resistance-high capacitance splanchnic circulation Compensatory response causing a high resistance-low capacitance extrasplanchnic circulation • Cirrhotic cardiomyopathy: Describes systolic dysfunction in the setting of HCO and low SVR, diastolic dysfunction, and supportive criteria (e.g., long QTc and abnormal chronotropy due to β1 receptor down-regulation). Pharmacologic and physiologic stress can unmask an impaired LVEF and elevated LVEDV (1)[A]. • SIRS/sepsis: Adequately fluid-resuscitated patients have a hyperdynamic circulation and low SVR. The extent of SVR reduction appears to be related to mortality (2)[B]. – Mechanisms of low SVR: A blunted rise of intracellular Ca2+ in vascular smooth muscle by activated KATP channels, increased expression of NO synthase, and depletion of vasopressin stores due to sustained baroreflex stimulation (2)[A]. – Septic cardiomyopathy presents as an isolated or combined diastolic and systolic dysfunction. The etiology is unknown but appears to include NO, TNF-α, and cytokines. Impaired LVEF is associated with poor prognosis in septic patients (2)[A]. – Increased troponins (nonischemic “leak”) predict LV dysfunction and mortality (2)[A]. • Hyperthyroidism: Decreased SVR combined with increased chronotropy and inotropy can result in a greater than 250%.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Ensure adequate perioperative organ/tissue perfusion and oxygenation. • The degree of circulatory derangement and type of surgery determine the invasiveness of monitoring and the acuity of postop care.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Anxiety • Palpitations, angina-like chest pain

• Dyspnea, orthopnea • Fatigue, poor exercise tolerance • Lower extremity swelling • Symptoms related to primary disease

History

Etiology of HCO, functional status, end-organ dysfunction, degree of circulatory compromise Signs/Physical Exam

• Tachycardia, tachypnea • Hypotension, wide pulse pressure • Jugular venous distention and hum • Hyperdynamic precordium • Midsystolic murmur (2nd and 3rd LICS), S3 • Bounding femoral artery pulses (pistol shots) • Warm extremities

TREATMENT HISTORY

• Treatment of primary etiology • Treatment of heart failure

MEDICATIONS

• α-1 Adrenergic agonist (phenylephrine, norepinephrine, midodrine) (3)[A] • Dopamine (dosed as α-1 agonist; lower doses act to lower the SVR) (3)[A] • Vasopressin, terlipressin (4)[A] • Catecholamine inotropes have decreased efficacy due to β1 receptor downregulation. Alternative inotropic agents include milrinone (phosphodiesterase inhibitor) and levosimendan (troponin C sensitizer to Ca2+) (4)[C]. • Diuretics, digoxin if in heart failure (1)[A] • Drugs specific to underlying cause

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• BMP to assess for acidosis, renal insufficiency • CBC: Pancytopenia, leukocytosis • LFTs, PT/INR, PTT: Hepatocellular integrity, ESLD, sepsis, liver function, coagulopathy • Fibrinogen, FDP: Fibrinolysis in sepsis, ESLD • ABG and lactate: Acid–base, hypoperfusion • Troponins: Myocardial ischemia or leak • BNP > 400 pg/ml implies CHF • CXR: Cardiomegaly, effusions, edema. • EKG: Tachycardia, ischemia, long QTc

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Poorly managed primary pathology (e.g., poorly controlled hyperthyroidism)

• Symptoms and signs of heart failure

CLASSIFICATIONS

No classification specific to HCO

TREATMENT PREOPERATIVE PREPARATION INTRAOPERATIVE CARE Choice of Anesthesia

• Neuraxial anesthesia is not recommended as it further reduces preload and afterload (4)[B]. • Peripheral nerve blocks should be considered, as appropriate. • No evidence favors either inhalational versus TIVA; both techniques reduce SVR (4)[A]. • Regardless of the anesthetic technique, vasopressors should be in line and ready for immediate administration. Monitors

• Standard ASA monitors may be adequate in minor surgery and in the absence of heart failure. • Invasive monitors: Indicated when compromised hemodynamics suggest heart failure. • Arterial line for continuous BP and metabolic assessment (serial ABGs, lactate levels, etc.). • Central venous pressure does not accurately reflect intravascular volume but is still used to guide volume therapy. Central venous access is optimal for vasoactive drug administration. • CO monitors: Most have limited absolute precision and accuracy in the setting of HCO but provide trends, which is clinically useful information for goal-directed volume therapy and hemodynamic management. – Pulmonary artery catheter thermodilution (PAC-TD): Despite its lack of precision and accuracy, it is still considered the clinical gold standard to validate novel CO monitoring modalities (5)[A]. Compared to Fick CO determination, PAC-TD systematically underestimates CO in the HCO range (>7 L/min). – Continuous venous oximetry: Central venous (SCVO2) and pulmonary artery mixed venous (SVO2) oximetry estimate adequacy of CO based on the difference between the oxygen

delivery (DO2) and VO2. It is of limited value in the setting of diffuse systemic AV

shunting as high oxygen saturation does not rule out organ hypoperfusion. – Arterial pressure-based CO monitors (APCOs) exhibit poor agreement in unstable hemodynamics compared to PAC-TD, may underestimate CO in HCO states, and is conceptually deficient when the artery used is in the setting of vasoconstriction (ESLD). – Esophageal Doppler (ED) estimates CO by measuring descending aortic flow velocity and has been used to successfully guide volume therapy; it has increased bias with increasing COs (5)[A]. – Transesophageal echocardiography (TEE): Visual assessment of ventricular filling, contractility, and regional wall motion. It is a useful hemodynamic monitor in HCO.

• Near-infrared spectroscopy (NIRS) continuously displays regional oxygen saturation (rSO2) of blood in target tissues. Conceptually, NIRS may be the best method of assessing adequacy of CO in low BP and shunt physiology but data is limited at this time.

Induction/Airway Management

• Most agents lower SVR, contractility, and MAP. Tachycardia increases VO2; bradycardia

decreases CO. • Etomidate has minimal decrease in SVR; however, adrenal suppression is possible even after a single dose. • Ketamine can drop SVR if catecholamines are depleted.

Maintenance

• Inhalational anesthesia or TIVA; no evidence exists to suggest superiority of one technique over another. • Volume and hemodynamic management can be guided by dynamic monitors (stroke volume variation, SVV), TEE, or tissue DO2 (tissue oximetry, lactate); not by a preset value of CO or

MAP (4)[B]. • Point of care testing for frequent ABGs and lactate • Protective ventilator lung strategies: – Low tidal volumes minimize the impact of positive pressure on the lungs but may be inadequate for SVV or CO estimates by APCOs. – Permissive hypercapnia should be carefully considered as it may aggravate an already low pH due to hypoperfusion (4)[A]. • Patients often cannot tolerate a full MAC of volatile anesthetic; however, this constitutes a high risk for recall; EEG or BIS monitoring may be appropriate.

Extubation/Emergence

Standard extubation criteria

FOLLOW-UP BED ACUITY

Telemetry, intensive care unit (ICU) based on underlying condition, hemodynamic status, and extent of surgery MEDICATIONS/LAB STUDIES/ CONSULTS

• Dependent on extent of surgery • ECG, cardiac enzymes, BNP if in HCO failure

COMPLICATIONS

• Heart failure, ischemia/MI, arrhythmias • Instability, dynamic LVOT obstruction • Decreased organ perfusion, circulatory shock

REFERENCES

1. Moller S, Henricksen J. Cirrhotic cardiomyopathy. J Hepatol. 2010;53:179–190. 2. Hunter J, Doddi M. Sepsis and the heart. Br J Anaesth. 2010;104(1):3–11.

3. Mehta PA, Dubrey SW. High output heart failure. QJM. 2009;102(4):235–241. 4. Eissa D, Carton EG, Buggy DJ. Anaesthetic management of patients with severe sepsis. Br J Anaesth. 2010;105(6):734–743.

5. Mayer J, Suttner S. Cardiac output derived from arterial pressure waveform. Curr Op Anaesth. 2009;22(6):804–808.

ADDITIONAL READING

• LeDoux D, Astiz M, Carpati C, Rackow EC. Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med. 2000;28(8):2729–2732.

See Also (Topic, Algorithm, Electronic Media Element) • Cardiac output • Hyperthyroidism • End-stage liver disease

CLINICAL PEARLS

• Decreased SVR is a part of a HCO state. • Cardiomyopathy may be masked by a low SVR. • Currently available monitors are often not accurate in HCO states; however, CO/SVR trending information can be clinically useful. • Organ perfusion is key to intraoperative management.

CARDIAC PACEMAKER CELLS Marek Postula, MD, PhD Piotr K. Janicki, MD, PhD

BASICS DESCRIPTION

• In the mammalian heart, three major structures create rhythmical impulses and are able to drive the heartbeat: The sinoatrial (SA) node, the atrioventricular (AV) node, and the Purkinje fiber network. • The SA node region serves as the primary (physiological) pacemaker, while the AV node and Purkinje fibers serve as secondary (or accessory) pacemakers. • Spontaneous (Phase 4) diastolic depolarization underlies the electrophysiological property of automaticity of cells in the SA and AV nodes, His–Purkinje system, coronary sinus, and possibly the pulmonary vein. PHYSIOLOGY PRINCIPLES

• SA node. Initiates the heart beat and sets the rate and rhythm of cardiac contraction. SA nodal cells are characterized as having no true resting potential, but instead generate regular, spontaneous action potentials. – The ionic mechanism underlying the pacemaker depolarization is the activation of the hyperpolarization-activated current (If); this current is crucial in the generation of diastolic

depolarization and hence of spontaneous activity. Depolarizing current is carried into the cell primarily by relatively slow Ca2+ currents. – The action potential, initiated in the center of node, propagates to the periphery of the node, and then into the musculature of the terminal crest. – In the center of the node, the action potential is slow and small compared with the action potential in the surrounding atrial muscle. – Autonomic regulation. The nodal region has an abundance of parasympathetic and sympathetic nerve endings. Acetylcholine increases (makes more negative) the transmembrane resting potential and reduces the spontaneous Phase 4 (diastolic) slope, thereby tending to reduce the rate at which depolarization occurs. Acetylcholine also tends to prolong refractoriness of SA node cells. Excessive parasympathetic influence may induce marked sinus bradycardia, sinus arrest, and exit block. Catecholamines (norepinephrine and epinephrine) increase the rate of Phase 4 depolarization, thereby increasing the sinus rate. The sympathetic autonomic nervous system (ANS) increases the heart rate and may reverse sinus arrest and SA exit block. During aging, the SA node structure undergoes remodeling associated with an augmentation of collagen content. Parasympathetic influence on SA node chronotropism progressively diminishes with increasing age. Maintenance of an appropriate heart rate and chronotropic responsiveness in older individuals is increasingly dependent on the

integrity of the sympathetic tone. • AV node. From the SA node, the wave of depolarization spreads across the atria to the AV node. The AV node sets the appropriate frequency-dependent conduction delay between the atria and ventricles. It also limits ventricular activation during atrial tachyarrhythmias, thereby protecting the ventricular rhythm. – Action potentials have relatively low resting potentials, slow upstrokes (Ca2+ dependent), and properties of refractoriness that persist well after repolarization has been completed (i.e., time-dependent refractoriness). – Dromotropic responsiveness in the resting patient is under relatively balanced sympathetic and parasympathetic neural influence. The relationship between ANS control of the SA rate and AV conduction properties appears to foster both maintenance of 1:1 AV conduction and a relatively optimal AV conduction interval. Parasympathetic predominance (i.e., sleep, very fit resting subjects) markedly enhances AV nodal dromotropic properties; in the extreme this can be associated with transient complete AV nodal block. AV node can become dominant in case of sympathetic block or failure. • Purkinje fibers. His bundle and bundle branches are composed of cells with larger surface area, more negative resting membrane potentials, and faster (Na+ dependent) action potentials than those of the AV node. – Automaticity in Purkinje fibers is slower than in the SA node and AV node. Depending on the species considered, the pacemaking rate in Purkinje fibers varies between 25 and 40 beats/minute, which is usually sufficient to set a viable cardiac output. – The Purkinje fibers network can pace the heart in cases of complete AV block. – Action potentials propagate within thin Purkinje fiber bundles from base to apex before activation of the surrounding myocytes occurs. • Purkinje fibers appear to be more resistant to ischemia than ordinary myocardial fibers.

ANATOMY

• SA node. Situated laterally in the epicardial groove (less than 1 mm from the epicardial surface) of the sulcus terminalis near the right atrium–superior vena cava junction. In addition to the SA node, spontaneously active pacemaker cells can also be found in the area of the crista terminalis, the left and right branch of the SA ring bundle, and the interatrial septum. – The SA node is a spindle-shaped structure with a fibrous tissue matrix that is comprised of closely packed cells with a wide variety of morphologies. Only the spindle- and spidershaped cells exhibit the typical electrophysiological characteristics of pacemaker cells. – 10–20 mm long, 2–3 mm wide, and thick, tending to narrow caudally toward the inferior vena cava. – Besides pacemaker cells, the SA node also contains atrial cells, fibroblasts, and adipocytes. – Arterial supply to the SA node arises from the right coronary artery 55–60% of the time and the left circumflex artery 40–45% of the time; this is often referred to as right or left dominance • AV node. A superficial structure lying just beneath the right atrial endocardium, anterior to the ostium of the coronary sinus, and directly above the insertion of the septal leaflet of the

tricuspid valve. – It is located at the apex of a triangle (triangle of Koch) formed by the tricuspid annulus and the tendon of Todaro, which originates in the central fibrous body and passes posterior through the atrial septum. – The cells are small and dispersed in a complex fibrous tissue matrix with relatively large extracellular space. – Arterial supply to the AV node typically arises from a branch of the right coronary artery 80–85% of the time. • Purkinje fibers. Cells are found in the His bundle and bundle branches; they cover much of the endocardium of both ventricles. In humans, they penetrate only the inner 1/3rd of the endocardium. Purkinje fibers tend to be less concentrated at the base of the ventricle and at the papillary muscle tips.

DISEASE/PATHOPHYSIOLOGY

• Sinus node dysfunction (sick sinus syndrome) includes the following: – Abnormalities of sinus node impulse generation – Disturbances of impulse emergence into the atrium – Abnormal impulse transmission within the atria (and in some cases from the atria to the ventricles) – Increased susceptibility to atrial tachycardias (particularly atrial fibrillation) and chronotropic incompetence – Inappropriate sinus tachycardia – Persistent or inappropriate sinus tachycardia includes abnormal enhanced automaticity within the SA node or nearby atrial regions – Bradycardia–tachycardia syndrome includes periods of bradyarrhythmia interspersed with bouts of atrial fibrillation, or less commonly other paroxysmal primary atrial tachycardias • AV conduction disturbances include AV blocks (first degree, second degree, third degree) – First- and second-degree type 1 AV blocks are most often the result of conduction disturbances at the level of the AV node and are frequently attributable to ANS influences. – In the presence of a narrow QRS complex, first-degree AV block is due to AV nodal delay in more than 85% of patients and due to delay within the His bundle in less than 15%. – Complete heart block is almost always associated with structural heart disease and, more often is associated with a wide QRS morphology. • Drug effects – Cardiac glycosides: First- or second-degree type 1 AV block occurs as a result of glycosideinduced enhanced vagal tone at the AV node. – Beta-adrenergic blockers result in AV nodal conduction slowing, block, or both by diminishing sympathetic effects on the AV junction. – Calcium channel blockers (particularly verapamil and diltiazem) and most antiarrhythmic drugs (especially from class 1C) act directly to slow conduction in the AV node. – Quinidine and disopyramide manifest prominent vagolytic actions, which tends to counterbalance their negative dromotropic direct effects

PERIOPERATIVE RELEVANCE

• Loss of pacemaker activity from the SA node may result in circulatory collapse, necessitating

the implantation of an electronic pacemaker. • “Intrinsic” sinus node dysfunction is related to idiopathic degenerative and fibrotic changes associated with the aging process. • “Extrinsic” sinus node dysfunction can be caused by beta-adrenergic blockers, calcium channel blockers, membrane-active antiarrhythmics, and digitalis. • Drugs can alter SA node function as a result of direct pharmacologic effects (e.g., flecainide, sotalol, and verapamil) or indirectly via the autonomic nervous system (e.g., betaadrenergic blockers), or both (e.g., quinidine, disopyramide, propafenone, amiodarone, and digitalis). • Parasympathetic predominance can result in sinus bradycardia, sinus pauses, SA exit block, and slow ventricular responses in atrial fibrillation. • Assessment of SA node function: – Responses to pharmacologic interventions (e.g., autonomic blockade) – Neural reflexes (e.g., carotid sinus massage, Valsalva maneuver, heart rate response to upright tilt) • Responses to induced hypotension (e.g., by administration of amyl nitrite)

GRAPHS/FIGURES

FIGURE 1. Schematic organization of the pacemaker cells in the conduction system of the heart.

FIGURE 2. Anatomical localization of the pacemaker cells and conduction system in the human heart. The AV node tapers

down into the bundle of His, which passes into the ventricular septum and divides into two bundle branches, the left and right bundles.

FIGURE 3. SA nodal action potentials are divided into three phases. Phase 4 is the spontaneous depolarization (pacemaker

potential) that triggers the action potential once the membrane potential reaches threshold between –40 and –30 mV. Phase 0 is the depolarization phase of the action potential. This is followed by Phase 3 repolarization. Once the cell is completely repolarized at about –60 mV, the cycle is spontaneously repeated.

FIGURE 4. Effects of Parasympathetic (Vagal) and Sympathetic Nerve Activation on SA Nodal Action Potentials. Dashed line represents a normal action potential.

REFERENCES

1. Dobrzynski H, Boyett MR, Anderson RH. New insights into pacemaker activity: Promoting understanding of sick sinus syndrome. Circulation. 2007;115:1921–1932. 2. Mangoni ME, Nargeot J. Genesis and regulation of the heart automaticity. Physiol Rev. 2008;88:919–982. 3. Anderson RH, Yanni J, Boyett MR, et al. The anatomy of the cardiac conduction system. Clin Anat. 2009;22:99–113. See Also (Topic, Algorithm, Electronic Media Element) • Bradycardia • Tachycardia • Authonomic nervous system • Sick syndrome

CLINICAL PEARLS

• Heart failure and atrial fibrillation may be associated with significant SA node dysfunction.

• SA node dysfunction can be caused by beta-adrenergic blockers, calcium channel blockers, membrane-active antiarrhythmics, and digitalis. • Complete heart block is almost always associated with structural heart disease. • First- and second-degree AV blocks can be caused by beta-adrenergic blockers, calcium channel blockers, membrane-active antiarrhythmics, and digitalis.

CARDIOGENIC PULMONARY EDEMA Eric W. Nelson, MD

BASICS DESCRIPTION

• Cardiogenic pulmonary edema (CPE) is the accumulation of fluid with a low protein content in the lung interstitium and alveoli. It results from the left ventricular (LV) output being lower than pulmonary and left atrial venous return. • CPE is the end-result of several different pathological processes that cause increased hydrostatic pressure. Alternatively, increased permeability is seen more commonly with primary pulmonary processes such as acute respiratory distress syndrome or acute lung injury (noncardiogenic pulmonary edema). • Analogy: The heart functions like a dam, and the lungs are the banks along the river. When the dam does not let the water through, the river rises, backs up, and overflows onto the banks. In CPE, the heart pump malfunctions and thus causes backup and overflow leading to edema in the lungs. EPIDEMIOLOGY Prevalence

Difficult to assess exact incidence; however, pulmonary edema occurs in 1–2% of the general population. Prevalence

CHF, a major cause of CPE, affects nearly 5 million Americans. Mortality

• In-hospital mortality: 15–20% • CPE resulting from an acute myocardial infarction (MI) has a 40% mortality; this can reach 80% when the patient is hypotensive. ETIOLOGY/RISK FACTORS

• Acute MI (1) • Severe myocardial ischemia • Cardiomyopathies (low ejection fraction) • LV volume overload • LV outflow obstruction (aortic stenosis) • Diastolic dysfunction • Acute mitral regurgitation • Left atrial myxoma • Atrial fibrillation, due to low LV filling

PHYSIOLOGY/PATHOPHYSIOLOGY

• LV pump dysfunction increases left atrial volume and pressure that transmits to the pulmonary vasculature. The increased hydrostatic pressures initially cause dilation and recruitment of pulmonary vessels, followed by extravasation into the interstitial space, and entry into alveoli. This manifests as follows: – Decreased pulmonary compliance – Atelectasis and decreased functional residual capacity; results in V/Q mismatching and increased Alveolar-artery (A-a) gradient – Increased work of breathing

PREVENTATIVE MEASURES

• Ischemia and infarction – Increase myocardial oxygen supply Increase the FIO2

Increase hemoglobin levels (if appropriate) Increase diastolic perfusion pressure Decrease heart rate (increases diastolic perfusion time) Avoid hyperventilation (which can cause vasospasm of the coronary arteries) – Decrease myocardial oxygen demand Decrease heart rate (as appropriate) Decrease contractility (as appropriate) Decrease preload (as appropriate) Decrease afterload (as appropriate Maintain sinus rhythm (if possible) – Cardiac catheterization and percutaneous intervention – Emergency coronary artery bypass surgery • Hypertensive emergency. Aggressively treat BP to decrease myocardial wall tension (and decrease oxygen consumption). Insert invasive monitors as needed • Diastolic dysfunction. Avoid volume overload, increase lusitropy (myocardial relaxation), maintain sinus rhythm (atrial kick is important for adequate end diastolic volumes) • Systolic dysfunction. Avoid volume overload, promote afterload reduction • Aortic stenosis. Maintain normal sinus rhythm, slow heart rate, adequate diastolic perfusion pressures, and volume status (preload dependent) • Mitral stenosis. Maintain normal sinus rhythm, slow heart rate, avoid volume overload. • Atrial fibrillation. Convert to a sinus rhythm if possible; if not, maintain rate control.

PREOPERATIVE ASSESSMENT • Under general anesthesia, the intraoperative diagnosis may be difficult; many signs and symptoms will be masked or are nonspecific. – There is usually a history of an acute cardiac or coronary event prior to its onset, or conversely volume overload in the setting of baseline cardiac dysfunction. – Hypoxia and desaturation can result from atelectasis. Auscultation can reveal crackles, rales, wheezing, and murmurs. – Arterial blood gas measurements can reveal an increased A-a gradient.

– Increased sympathetic tone can result in tachycardia and hypertension. However, in the setting of severe LV dysfunction, hypotension may be present. – S3 gallop or jugular venous distention may be observed. – Pink, frothy sputum in the endotracheal tube or laryngeal mask airway may be seen. • Invasive monitoring – PCWP is useful in differentiating causes of pulmonary edema, as CPE will usually have a PCWP >18 mm Hg, pulmonary edema from other causes typically has a PCWP <18 mm Hg. – Transesophageal echocardiogram (TEE) is useful when a patient is under anesthesia to help determine if the cause of pulmonary edema is from a cardiac cause. Ventricular dysfunctions (wall motion, ejection fraction), ventricular pathology (stenosis, regurgitation), and volume status can be determined.

DIFFERENTIAL DIAGNOSIS

• Aspiration • Pulmonary embolism • Sepsis • Anaphylaxis • Acute asthma exacerbation • Chronic obstructive pulmonary disease • Pneumonia • Pneumothorax • Acute respiratory distress syndrome

TREATMENT • Should be aimed at the underlying cause while supporting cardiac pump function (2). • Preload reduction decreases the volume that the heart needs to pump forward; akin to decreasing the river flow to the dam. – Venodilators. Nitroglycerin is fast acting and easily titratable (increases capacitance, does not decrease intravascular volume). – Diuretics. Loop diuretics such as furosemide reduce intravascular volume, but require ∼20 minutes for onset. In the setting of poor renal perfusion, it may be even longer. – Hemodialysis may be necessary in the setting of renal failure and volume overload. • Afterload reduction improves forward flow (stroke volume and hence cardiac output) for a given contractility; it decreases wall tension and myocardial oxygen demand. This is accomplished via vasodilators (3). – Nitroprusside is a potent arterial dilator and easily titratable (4). – Intravenous calcium channel blockers may also be utilized. – Volatile anesthetics • Inotropic support should be considered when CPE is refractory to preload and afterload reduction, or when hypotension prevents the use of these strategies. Improved pump function allows improved management of venous return and forward flow with resultant: – Decreases in LV end-diastolic pressure (LVEDP) and volume; results in decreased wall

tension (decreased radius, as per LaPlace’s Law). – Improvement in coronary perfusion during diastole (CPP = MAP–LVEDP) – Improvement in cerebral and systemic perfusion – However, this comes at the cost of increased myocardial oxygen consumption secondary to enhancing the contractile state. • Inotropic agents include the following: – Dobutamine is a β-1 agonist; it causes a mild reduction in afterload that helps to increase cardiac output. – Milrinone is a phosphodiesterase inhibitor, which increases inotropy and decreases both SVR and PVR (5). – Dopamine has β and alpha effects depending on the dosage. At high doses, it can cause tachycardia and has arrhythmogenic potential. – Norepinephrine is a potent alpha-1 agonist with some β activity. It is typically reserved for patients with refractory hypotension as it tends to cause a much greater increase in afterload than the other inotropes. • Oxygenation – Increase the FiO2 – Increase hemoglobin levels with packed red blood cell transfusion, if appropriate – PEEP should be optimized in an attempt to keep the SpO2 >90%

FOLLOW-UP • Treatment of the underlying cause should be the initial step in managing these patients once they are stabilized. • Any arrhythmias must be corrected. • If CPE is caused by an acute valvular dysfunction, emergent valve surgery is required. • CPE from an acute MI typically requires either aggressive medical management, percutaneous intervention, or bypass surgery • Left ventricular assist device (LVAD) or heart transplants may be warranted.

REFERENCES

1. eConte P, Coutant V, Nguyen JM, et al. Prognostic factors in acute cardiogenic pulmonary edema. Am J Emerg Med. 1999;17(4):329–332. 2. Mattu A, Martinez JP, Kelly BS. Modern management of cardiogenic pulmonary edema. Emerg Med Clin North Am. 2005;23(4):1105–1025. 3. Annane D, Bellissant E, Pussard E. Placebo-controlled, randomized, double-blind study of intravenous enalaprilat efficacy and safety in acute cardiogenic pulmonary edema. Circulation. 1996;94(6):1316–1324. 4. Dupuis J. Nitrates in congestive heart failure. Cardiovasc Drugs Ther. 1994;8(3):501–507. 5. Karlsberg RP, DeWood MA, DeMaria AN. Comparative efficacy of short-term intravenous infusions of milrinone and dobutamine in acute congestive heart failure following acute myocardial infarction. Milrinone-Dobutamine Study Group. Clin Cardiol. 1996;19(1):21–

30. 6. Gropper MA, Wiener-Kronish JP, Hashimoto S. Acute cardiogenic pulmonary edema. Clin Chest Med. 1994;15(3):501–515. 7. Teerlink JR. Overview of randomized clinical trials in acute heart failure syndromes. Am J Cardiol. 2005;96(6A):59G–67G.

ADDITIONAL READING • www.uptodate.com

See Also (Topic, Algorithm, Electronic Media Element) • Myocardial oxygen demand • Myocardial oxygen supply • Atrial fibrillation • Coronary artery disease

CODES ICD9 428.1 Left heart failure ICD10 I50.1 Left ventricular failure

CLINICAL PEARLS

• CPE carries a high mortality. Treatment should focus on the underlying cause, while supporting pump function, and providing supportive measures as appropriate. – Oxygenation should be optimized by titrating the FiO2 and PEEP to keep the SpO2 >90% – Rate control, maintenance of sinus rhythm, preload reduction, and inotropic support

CARDIOPLEGIA Ali Salehi, MD

BASICS DESCRIPTION

• Cardioplegia is a specialized solution that is delivered to the myocardium during cardiopulmonary bypass (CPB) to cease electrical activity and hence mechanical function. It – Brings the heart to a standstill and provides a quiet operating environment for the surgeon – Decreases oxygen (O2) demand by decreasing electrical activity and mechanical contraction – Supplies the myocardium with O2 and nutrients in order to protect it from ischemic injury

PHYSIOLOGY PRINCIPLES

• Cardiac myocardium has a high O2 demand and requires a high, sustained supply of O2 and nutrients. – Normal myocardium: 8 mLO2/100 g/min

– Empty beating heart: 5.6 mLO2/100 g/min – K+ arrested heart: 1.1 mLO2/100 g/min

– Myocardial arrest and cooling decreases consumption to 0.3 mLO2/100 g/min (1,2).

• Ischemia results when there is an imbalance in O2 supply and demand. O2 delivery depends on the following: – Hemoglobin concentration – Arterial O2 saturation

– Blood flow to the heart. This is dependent on the coronary perfusion pressure and is equal to diastolic blood pressure minus the left ventricular end diastolic pressure. • Cardiac contractility is dependent on adenosine triphosphate (ATP). Aerobic metabolism produces 36 ATP for each glucose molecule; anaerobic metabolism produces only 2 ATP and also results in lactic acid and H+ accumulating in the myocardium (suppresses glycolysis). • Cardioplegia during CPB functions to: – Provide a quiet surgical field to facilitate the surgical procedure (arrest electrical activity and hence myocardial contractility). – Decrease myocardial energy requirements and O2 demand in order to protect and preserve myocardial function during the period in which aortic cross-clamp is placed and myocardial perfusion is disrupted. – Provide O2 and nutrients to the myocardium while it is ischemic (no coronary artery perfusion). – Of note: Myocardial arrest time can be prolonged or shortened by the administration of additional cardioplegia or washing out of cardioplegia.

• Composition of cardioplegia: Crystalloid or crystalloid and blood: – Crystalloid cardioplegia only contains dissolved O2 due to the lack of hemoglobin. Its O2 carrying capacity is sufficient to provide enough O2 to cold myocardium, hence, it

requires a hypothermic strategy for myocardial protection. Its composition can be altered by the addition of additives that replace substances present in blood cardioplegia. Intracellular solutions have a [Na+] similar to the intracellular [Na+]; this abolishes the Na+ gradient and thereby prevents action potentials and myocardial contraction. The lack of Ca++ further hinders myocardial contractility. Procaine chloride and magnesium chloride are added to provide membrane stability, and mannitol maintains the osmolarity of the solution. Today, it is mostly used for organ preservation in cardiac transplantation. Extracellular solutions have a [Na+] similar to the extracellular [Na+] but with a high [K+], 8–30 mmol/L, that is responsible for causing diastolic arrest of cardiac action potentials. Today, it is more commonly used during CPB. – Blood cardioplegia is made by mixing blood and crystalloid cardioplegia. The ratio of blood:crystalloid is typically 4:1, but may vary based on the practitioner or institution. It has a higher O2 carrying capacity because it contains hemoglobin and can be used for

both cold and warm cardioplegia. Cold cardioplegia, however, causes a left-shift on the oxyhemoglobin saturation curve; thus, hemoglobin has an increased affinity and will not offload O2 to tissues as readily. Benefits of blood cardioplegia include having natural

buffers, free radical scavengers, and colloids, thus decreasing the need for additives. Blood cardioplegia solution is used more commonly than crystalloid cardioplegia. The most recent meta-analysis of the current literature indicates that blood cardioplegia is associated with a decreased incidence of low cardiac output state and creatine phosphokinase isoenzyme MB (CK-MB) release, but there is no difference in the incidence of myocardial infarction or mortality (3). • Cardioplegia temperature, desired myocardial temperature, and protective strategies: The optimal myocardial temperature is dependent on the particular patient and surgery; it affects the choice between cold and warm cardioplegia as well as other protective strategies. – Cold (hypothermic) cardioplegia at a temperature of 4–10°C is typically administered to produce myocardial cooling. Myocardial metabolic rate and O2 consumption decrease by 50% for every 10°C drop in temperature; the greatest benefit is achieved at a myocardial temperature of 25°C. Further cooling of the heart will result in smaller reductions in O2

demand. Drawbacks of hypothermia include myocardial edema and injury that can result in post-CPB myocardial dysfunction (4). – Warm cardioplegia is used to achieve a “warm induction,” or arrest prior to the initiation of ischemia. Electrical and mechanical arrest results from a high [K+] of 20–25 mEq/L (decreases O2 consumption to ∼1.1 mLO2/100 g/min), while providing O2 and nutrients to the myocardium (maintains O2 supply). It can be used throughout the entire procedure

if prolonged ischemia is not anticipated. However, because it is not hypothermic, it does not aid with decreasing cellular metabolism. It also requires blood cardioplegia (contains

hemoglobin and hence a higher O2 carrying capacity) and continuous administration.

Studies have shown that warm cardioplegia results in a decreased incidence of myocardial dysfunction and impaired cardiac output in the post-bypass period, particularly in the setting of significant prebypass myocardial dysfunction and low ejection fraction (i.e., cardiogenic shock, progressing myocardial infarction, and advanced valvular disease) (4,5,6). • Route of delivery: – Anterograde delivery is through a cannula placed in the ascending aorta proximal to the aortic cross-clamp. Flow is usually adjusted to achieve and maintain a pressure of 70–100 mm Hg in the aortic root. A rapid rate or low perfusion pressure will result in uneven distribution of cardioplegia. – Retrograde delivery is through a cannula placed in the coronary sinus (CS). Right ventricular (RV) venous return enters the CS near the CS ostium or directly into the right atrium (RA) which may result in inadequate RV myocardial protection through retrograde cardiolegia. – Additionally, cardioplegia can be delivered directly in the coronary ostia (Ostial), or through the bypass grafts to the distal coronary arteries (7). • Frequency of delivery. Single dosing is appropriate when bypass time is short and there is no coronary disease. Multiple dose delivery is used in most cases, however, and is given to replace the solution washed away through noncoronary collateral flow. It is given for 1–2 minutes every 10–20 minutes. Advantages of multiple dose delivery include the following: – Maintain myocardial arrest – Maintain myocardial hypothermia (cold cardioplegia) – Supply substrates – Clear metabolites – Counteract myocardial edema • Additives. Counteract the potential myocardial injury and dysfunction during myocardial arrest and reperfusion. Blood cardioplegia needs fewer additives in comparison to crystalloid cardioplegia, as previously discussed. – Calcium reduces the risk of reperfusion injury. – Magnesium not only stabilizes the myocardial cell membrane but also antagonizes the effect of calcium (preventing the need to eliminate Ca++ from the solution). It has been shown that there is no benefit to adding magnesium to calcium-free cardioplegia. – Buffers. Natural (histidine, imidazole groups on proteins, bicarbonate) and synthetic buffers (THAM) are added to offset the accumulation of lactic acid in the myocardium during CPB. Blood cardioplegia contains only natural buffers. – Increasing osmolality to that of extracellular fluid helps prevent myocardial edema and preserve ventricular function. Mannitol, albumin, and glucose are used to increase the osmolarity of solutions. – Energy substrates. Addition of glutamate and aspartate can help replete the high-energy phosphates in the myocardium and preserve myocardial function.

ANATOMY

• Anterograde cannula is placed just proximal to the site selected for aortic cross-clamp in the

ascending aorta. The cannula has 3 ports, one for delivering cardioplegia, one for pressure monitoring, and one for venting. If the patient is undergoing aortic aneurysm repair or aortic valve surgery, anterograde cardioplegia can be delivered directly into the relative coronary ostia. • Retrograde cannula is placed through a small incision through the RA after the placement of the venous cannula. The surgeon feels the inferior vena cava–right atrial junction and guides the tip of the cannula into the CS ostium. This can also be guided by transesophageal echocardiography. Presence of a large Thebesian valve in the entrance of the CS can prevent the placement of the cannula. The cannula is advanced until resistance is felt or a pressure of >20 mm Hg is measured. This means that the cannula is wedged and is at the junction of the CS and great coronary vein; it should be pulled back 1 cm and secured. • The left ventricular free wall is perfused and cooled equally well by anterograde and retrograde techniques in the presence of a patent coronary vasculature. Subendocardial muscle is perfused as well as the epicardial muscle or even hyperperfused (Endo:Epi 1.4:1). If the left anterior descending artery is obstructed and anterograde cardioplegia is used, subendocardial muscle will be underperfused (Endo:Epi <0.2). Selective subendocardial hyperperfusion can be restored with retrograde cardioplegia (6). • Left ventricular septal cooling is more profound with retrograde cardioplegia because it reduces the septal blood flow. It has been suggested that this effect is due to a rich network of venovenous collateral vessels. Retrograde flow passes this network and cools the septum without nourishing the capillary bed. • Blood flow in the RV capillary bed is maintained with anterograde cardioplegia. Retrograde cardioplegia decreases RV perfusion by 20% in comparison to anterograde cardioplegia but moderate cooling (20°C) can be achieved.

PHYSIOLOGY/PATHOPHYSIOLOGY

In coronary artery bypass grafting, doses are alternatively given anterograde and retrograde. In mitral valve procedures, they are given mostly retrograde. PERIOPERATIVE RELEVANCE

• Anterograde cardioplegia is used first to induce rapid arrest and limit the total amount of perfusate used. It is started after initiation of bypass and before cross-clamping the aorta to ensure aortic valve competency. Transesophageal echocardiography can be used to determine left ventricular distension at this time. • A pressure of 70–100 mm Hg should be achieved during administration of anterograde cardioplegia. Pressure is transduced through the side port of the anterograde cardioplegia cannula. If the CS pressure rises during administration of anterograde cardioplegia, it indicates that the venous return from the coronary flow is entering the cannula tip. Pressure never exceeds 50 mm Hg because a portion of the venous return is drained directly into the RA and ventricle through the Thebesian veins. If arrest is not achieved within 1 minute, several reasons need to be considered: – Incomplete aortic cross-clamping. The cross-clamp may need to be adjusted or a new clamp used. – Aortic valve insufficiency (AI). If AI is mild, then increasing the cardioplegia flow to 500 cc/min will be sufficient. If significant, anterograde cardioplegia should be abandoned and

switched to retrograde. – Distortion of the noncoronary cusp by the venous cannula. In this situation, the venous cannula should be repositioned. – Inadequate venous drainage. Cardioplegia should be started after the collapse of the pulmonary artery to confirm adequate drainage. – Insufficient potassium in the cardioplegia solution • Retrograde cardioplegia is delivered at a rate of 200–250 cc/hr to achieve a pressure of 30– 50 mm Hg. It is important that the pressure in the system and in the cannula be monitored closely. A CS pressure >20 mm Hg after insertion, or >50 mm Hg while on pump, means that the cannula is too far or wedged and needs to be pulled back and resecured. The cannula has a self-inflating balloon 1.8 cm in length with low intramural pressure and flows of 200–250 cc/hr to prevent barotrauma during infusions. • Return of electromechanical activity after 2–5 minutes of administration of cardioplegia indicates that the cardioplegia solution was washed away by noncardioplegic blood. This could be due to inadequate venous drainage, low perfusate potassium concentration, or incomplete aortic clamping. • Preparation for separation from CPB. The temperature is raised to 37°C and reperfusion is done with substrate enriched blood cardioplegia to buffer acidosis and limit the calcium load. Rewarming is started about 5 minutes before warm reperfusion. Warm reperfusate has a low potassium concentration (8–10 mmol/L) and is rich in substrates (aspartate, glutamate), CPD (to reduce calcium), and buffers (THAM). The first dose is given via anterograde cardioplegia and then alternated between anterograde and retrograde cardioplegia; the flow rate is 150 cc/hr for 3–5 minutes. The aortic cross-clamp is then removed and electromechanical activity usually resumes within 1–2 minutes. If this does not occur, it is indicative of a high serum and myocardial K+. Usually furosemide (0.5 mg/kg) and 1 g CaCl2 are given to ease the return of rhythm and contractility.

REFERENCES

1. uckberg GD, Braizer JR, Nelson RI, et al. Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. I. The adequately perfused beating, fibrillating, and arrested heart. J Thorac Cardiovasc Surg. 1977;73:87– 94. 2. Sink JD, Hill RC, Attarian DE, et al. Myocardial blood flow and oxygen consumption in the empty-beating, fibrillating, and potassium arrested hypertrophied canine heart. Ann Thorac Surg. 1983;35:372–379. 3. Hayashida N, Economides JS, Weasel RD, et al. The optimal cardioplegic temperature. Ann Thoracic Surg. 1994;58:961–971. 4. Rosenkranz ER, Buckberg GD, Mulder DG, et al. Warm induction of cardioplegia with glutamate enriched blood in coronary patients with cardiogenic shock who are dependent on inotropic drugs and intra-aortic balloon pump support: Initial experience and operative strategy. J Thorac Cardiovasc Surg. 1983;86:507. 5. aylaor CD, Lichtenstein SV, Fremes SE, et al. Randomised trial of Normothermic vs Hypothermic coronary bypass surgery. Lancet. 1994;343:559–563.

6. Buckberg GD. Antegrade/retrograde blood cardioplegia to ensure cardioplegic distribution: Operative techniques and objectives. J Card Surg. 1989;4(3):216–238. 7. Jacob S, Kallikourdis A, Sellke F, et al. Is blood cardioplegia superior to crystalloid cardioplegia? Interact Cardiovasc Thorac Surg. 2008;7:491–498.

ADDITIONAL READING

• Hensley FA, Martin DE, Gravlee GP, ed. A Practical Approach to Cardiac Anesthesia, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2008:604–624. • Shiroishi MS. Myocardial perfusion: The rebirth of potassium based cardioplegia. Tex Heart Inst J. 1999;26(1):71–86.

See Also (Topic, Algorithm, Electronic Media Element) Cardiopulmonary bypass

CLINICAL PEARLS

Blood cardioplegia is most commonly used for CPB procedures; the choice between warm and cold solution depends on the procedure and patient factors; additives are surgeon and center dependent.

CARDIOPULMONARY BYPASS Sascha Beutler, MD, PhD Daniel Castillo, MD

BASICS DESCRIPTION

• Cardiopulmonary bypass (CPB) machines temporarily take over the function of the heart and lungs. It is often referred to as a “heart-lung-machine.” – It redirects venous blood return away from the heart to the bypass machine where it adds oxygen and removes carbon dioxide. It returns the blood to the systemic circulation via a large artery. – Nearly all blood flow through the heart and the lungs stops. – Machines are operated by allied health professionals known as perfusionists. • Surgical procedures in which CPB are used: – Coronary artery bypass surgery – Cardiac valve repair and/or replacement – Repair of large septal defects – Repair and/or palliation of congenital heart defects – Repair of some large aneurysm (cerebral aneurysm, aortic aneurysm) – Pulmonary thrombectomy – Heroic measures when oxygenation or perfusion of organs cannot be maintained by other means (e.g., local anesthetic systemic toxicity, anterior mediastinal mass). PHYSIOLOGY PRINCIPLES

• Basic circuit of the CPB machine: – Venous cannulae are placed in the right atrium and/or in the inferior or superior vena cava to receive and redirect the patient’s blood away from the heart and lungs into a venous reservoir. – Oxygenator: From the venous reservoir, the blood passes through an oxygenator where oxygen is added (membrane oxygenators are less traumatic than bubble oxygenators). – Heat exchanger: The blood then passes through a heat exchanger that functions to cool or warm the patient to the desired temperature. – Main pump: either a roller head pump or a centrifugal pump. Roller pump: The pump console is made of several rotating motor-driven pumps that peristaltically “massage” the tubing. This action gently propels the blood through the tubing. Centrifugal pump: By altering the speed of revolution of the pump head, blood flow is produced by centrifugal force. This type of pumping action is considered by many to be superior to the action of the roller pump because it is thought to produce less blood damage. – Arterial cannula: Placed in the ascending aorta; the main pump returns the blood through

an arterial cannula to the patient’s systemic circulation. – Arterial line filter: Is incorporated in the CPB circuit to minimize the embolic load delivered to the patient. • Other components of CPB Machine: – “LV vent” is a cannula that suctions blood out of the left ventricle to prevent its dilatation (per LaPlace’s law, Tension = {Pressure * Radius}/Wall thickness; increases in radius increase tension and myocardial oxygen consumption). The blood originates from Thebesian and bronchial veins that empty directly into the left ventricle. – “Cardiotomy suction” is a suction cannula that removes and salvages undiluted or “clean” blood from the open cardiac chambers or the surgical field. – “Cellsaver” system collects and washes red blood cells from diluted field blood and blood that has been exposed to potentially harmful elements (e.g., inflammatory cytokines). – “Cardioplegia pump” administers a cardioplegic solution. • Monitoring and access: – Arterial line is placed prior to initiation of CPB: The flow on bypass is usually nonpulsatile and thus a noninvasive BP cuff will not work. – Large-bore intravenous access is also established in case of significant fluid shifts and/or blood loss prior to or after CPB. – Central venous access is routinely placed after induction; a pulmonary artery catheter (PAC) may be considered. – Transesophageal echocardiography probe is placed as indicated by the procedure in the absence of contraindications. • Anesthetic management: – Balanced anesthesia with shorter-acting narcotics (fentanyl), short-acting intravenous agents, such as propofol, and modern volatile agents are utilized. Volatile agents appear to improve cardiac cell conditioning when administered prior to the onset of ischemia. – High-dose narcotic techniques are not commonly used today. – Supplemental techniques have increased in popularity (e.g., paraspinal blocks) to reduce the use of systemic agents, improve analgesic control, and improve postoperative pulmonary function.

DISEASE/PATHOPHYSIOLOGY

• Systemic inflammatory response syndrome (SIRS): can result from cardiac surgery with CPB. – Possible causes include contact of the blood components with the artificial surface of the bypass circuit, ischemia-reperfusion injury, endotoxemia, and operative trauma. – Data indicate that a complex sequence of events leads to the activation of leukocytes and endothelial cells, which is responsible for cell dysfunction in different organs. – There may be some benefit of steroid use in patients undergoing CPB (see additional reading). • Complications of CPB (3)[B]: – Capillary leak syndrome secondary to inflammatory response (see above) – Hemolysis – Clotting of blood can block the circuit (particularly the oxygenator) or send a clot into the patient. – Air embolism

– Exsanguination (loss of blood perfusion of tissues) if a line becomes disconnected. – Type I CNS events in 3–6% of patients. – Long-term cognitive dysfunction in up to 15% of patients. – Acute respiratory distress syndrome in up to 1.5% of patients. – Renal dysfunction, with 1–2% of patients requiring hemodialysis. • As a consequence, CPB is only used during the several hours a cardiac surgery may take. Most oxygenators come with a manufacturer’s recommendation that they are only used for a maximum of 6 hours, although they are sometimes used for up to 10 hours. When longer periods of cardiopulmonary support are required, extra- corporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD) should be utilized.

PERIOPERATIVE RELEVANCE

• Initiation of bypass is defined as the moment that the patient’s venous blood is allowed to flow through the venous cannula, away from the heart into the bypass machine. A clamp is typically placed on the venous cannula while preparing for CPB; thus removal of the clamp usually marks initiation. – Use of CPB requires suppression of the clotting cascade with heparin because the components of the bypass pump and the surgical wound are powerful stimuli for thrombus formation. – Heparin is given intravenously before placement of the aortic cannula and the activated clotting time (ACT) is checked; the targeted ACT varies with the type of CPB used (heparin-coated versus nonheparin coated) and the type of surgical procedure. – After acceptable pump flows have been achieved and the mean BP is stabilized, the aorta is cross-clamped, cold cardioplegia (see below) is infused, and the heart is also topically cooled with a saline slush solution to stop it from beating. • Cardioplegia is a solution that contains a high concentration of potassium and other electrolytes. It is designed to arrest and protect the heart muscle. The solution is typically administered every 20–30 minutes throughout the on-bypass time when there is no blood flow through the heart. – Anterograde cardioplegia is administered through the coronary artery os and the flow is anterograde. – Retrograde cardioplegia is administered through a catheter in the right atrium directly into the coronary sinus. The flow is retrograde through the coronary veins. • Optimal conduct of CPB: – Currently, the management of patients during CPB varies substantially by institution and practitioner (surgeon, anesthesiologist, perfusionist involved). – Evidence-based guidelines for best perfusion practices have been developed (1)[A,B], (2) [A]. The guidelines describe physiologic parameters (mean arterial BP, pump flow rate, hematocrit, temperature) and technologies (heparinized versus nonheparinized circuits, arterial line filters, pulsatile versus nonpulsatlie pumps, centrifuge versus roller pumps) that may optimize perfusion. • Alpha stat versus pH stat: – Alpha stat arterial blood gases are not temperature corrected. During hypothermia on bypass, an alkaline shift occurs as carbon dioxide leaves the gas form and dissolves in the blood (less kinetic energy to keep in gas form; resulting in decreased PaCO2). This leads to

a leftward shift of the oxyhemoglobin dissociation curve that remains uncorrected; carbon dioxide is not added to the system and total body carbon dioxide remains the same. Alpha stat is most commonly used in adults. – pH stat arterial blood gases are temperature corrected. Carbon dioxide is added to the oxygenator to correct for the alkaline drift at lower temperatures and increases the PaCO2

to normal levels. This counteracts the leftward shift of the oxyhemoglobin dissociation curve. It is most commonly used in neonatal and infant cardiac surgery as it may offer neurologic protection for this patient population. • Comparison of adult and pediatric CPB: There are significant differences in the conduct of CPB between adult and pediatric patients (see Table 1). Table 1. Comparison of adult versus pediatric cardiopulmonary bypass

• Deep hypothermic circulatory arrest (DHCA) describes maintaining the body without any perfusion (blood flow). – It is most frequently used in pediatric cardiac surgery and aortic arch aneurysm repairs in adults. – The patient is put on the CPB and cooled to induce total body hypothermia, which is the prerequisite for initiation of DHCA. – Additional measures are instituted in an attempt to further reduce the metabolic requirement of the brain and provide brain protection during DHCA: Ice packing of the head, administration of barbiturates and mannitol. – Finally, blood flow to all organs, including the brain, is stopped. – In adults, DHCA may offer brain protection for up to 30–45 minutes. • Termination of CPB: – Weaning from CPB is only begun once the patient’s core temperature is adequate (about 36.5°C) and ventilation is re-established. – The aortic cross-clamp is removed and the heart beat most often resumes spontaneously; temporary pacing wires can be used if heart rate is inadequate. – Weaning from CPB is usually done gradually: The pump flow rates are slowly reduced, while the amount of blood flow back into the heart is slowly increased at the same time (“partial bypass”). – Once the patient is completely off CPB and vital signs are stable, venous and arterial cannulae are removed. – Protamine is then administered to reverse the heparin-induced anticoagulation. Always start with a test dose of protamine (typically 10 mg IV) before giving the full dose in case of an allergic reaction (severe pulmonary hypertension requiring reinstitution of the CPB).

REFERENCES

1. Murphy GS, Hessel EA II, Groom RC. Optiomal perfusion during cardiopulmonary bypass: An evidence-based approach. Anesth Analg. 2009;108(5):1394–1417. 2. Oakes DA, Managno CTM. Cardiopulmonary bypass in 2009: Achieving and circulating best practices. Anesth Analg. 2009;108(5):1368–1370. 3. Shann KG, Likosky DS, Murkin JM, et al. An evidence-based review of the practice of cardiopulmonary bypass in adults: A focus on neurologic injury, glycemic control,

hemodilution, and the inflammatory response. J Thorac Cardiovasc Surg. 2006;132:283– 290.

ADDITIONAL READING

• Conolly S, Arrowsmith JE, Klein AA. Deep hypothermic circulatory arrest. Contin Edu Anaesth Crit Care Pain. 2010;10:138–142. • Whitlock RP, Chan S, Devereaux PJ, et al. Clinical benefit of steroid use in patients undergoing cardiopulmonary bypass: A meta-analysis of randomized trials. Eur Heart J. 2008;29:2592–2600.

See Also (Topic, Algorithm, Electronic Media Element) • Coronary artery disease • Coronary artery bypass grafting • Circulatory arrest • Cardioplegia • Left ventricular assist device • Postoperative cognitive dysfunction • pH measurements

CLINICAL PEARLS

• CPB is a technique that temporarily takes over the function of the heart and lungs. • Certain surgical procedures are only possible to perform with the help of CPB. • CPB carries its own pathophysiology and complications. • There are significant differences in the indications and the conduct of CPB in adult and pediatric patients. • Evidence-based practice guidelines have been developed to optimize perfusion and outcome.

CAROTID BODY

Robert S. Fitzgerald, LittB, STB, MA, STM, PhD

BASICS DESCRIPTION

• The carotid body (CB) comprises chemoreceptors and their supporting cells at the bifurcation of the carotid artery. It functions to detect oxygen and carbon dioxide partial pressures as well as changes in pH, glucose, and temperature. • From the available literature, the CB was first reported in 1743 in a dissertation from the lab of the famous German physiologist, Albrecht von Haller. In 1938, Corneille Heymans received the Nobel Prize in Physiology or Medicine for his discovery of the role carotid and aortic mechanisms played in cardiopulmonary control. Heymans’ work owed a great debt to the pioneering histological work of Fernando De Castro who knew the difference between the CB and carotid sinus before the Heymans’ group (1). • The CB is sometimes confused with the carotid sinus, located at the base of the internal carotid artery; this latter structure is the principal detector and regulator of BP in mammals. • The CB, however, is arguably the most important interoreceptor in humans.

PHYSIOLOGY PRINCIPLES

• In human subjects, the CB is football-shaped with a volume of ∼12 mm3. The human CB weighs ∼14 mg but has an enormous blood flow, the highest of any organ measured. • The CB “tastes” the blood; that is, it is sensitive to qualitative changes in arterial blood composition. – When PaO2 or glucose drops, carbon dioxide tension (PaCO2) or hydrogen ion rises. The

neurotransmitter-containing chemosensitive glomus cells in the CB become depolarized and extracellular calcium rises in these cells. This provokes the release of excitatory (acetylcholine, adenosine triphosphate [ATP]) and inhibitory (dopamine) transmitters. – Serotonin and GABA, slower acting agents, are subsequently released (2). These neurotransmitters cross a synaptic-like cleft between the glomus cell and the abutting sensory afferent neuron, a branch of the glossopharyngeal nerve to bind to appropriate receptors. – The afferent neurons have their cell bodies in the petrosal ganglion and insert into nucleus tractus solitarii in the medulla. – The neurotransmitters also bind to autoreceptors on the glomus cells to promote or attenuate further release of the agents. • Stimulation of the CB initiates an impressive array of systemic reflex responses. – Pulmonary Increase in tidal volume Increase in respiratory frequency Increase in FRC (a static lung volume) Increase in airway resistance

Increase in secretions Decrease in pulmonary vascular resistance. – Cardiovascular Increase in sympathetic nerve output leading to tachycardia after an initial brief bradycardia Peripheral vasoconstriction Some of the cardiovascular responses are modified by the stimulated lung receptors due to the hyperpnea (increase in depth and rate of respiration). – Endocrine Release of some adrenal medullary contents as well as 17-OH corticosteroids Increase in plasma renin – Renal. CB stimulation increases renal sodium and water excretion in normoxic mammals. Bilateral CB denervation abolishes the natriuresis (3).

ANATOMY

Located bilaterally at the bifurcations of the common carotid arteries into their external and internal branches. DISEASE/PATHOPHYSIOLOGY

• Respiratory concerns – Obstructive sleep apnea (OSA). This condition, which affects over 11 million Americans including children, results from the relaxing and collapse of the upper airway muscles during sleep. Since metabolism continues, oxygen is consumed and PaO2 falls. Likewise CO2 is produced and PaCO2 rises.

This modest form of asphyxia strongly stimulates the CBs first; this provokes a minimal arousal and taking in of a breath. The stimulus to the CB also provokes a significant increase in sympathetic nervous system (SNS) output. This is not attenuated by input from the stretch receptors in the lung since the subject is apneic. As a consequence of the increased SNS output, heart rate and contractility increase as well as vascular resistance in some beds. This results in an increase in BP, a very undesirable consequence for subjects who have suffered a previous stroke. BP never returns to normal. The nocturnal hypertension frequently carries over into the daylight hours. Episodes of OSA can occur as frequently as 30–40 times per hour. Hypoxia also increases pulmonary arterial pressure by local mechanisms; this is somewhat attenuated by CB stimulation. – Sudden infant death syndrome. Though this condition has been greatly reduced by proper positioning of the infant during sleep, the CBs are still thought to function as above in the periodic apneas observed in children throughout their first year of postnatal life as their respiratory control system undergoes development. • Cardiovascular concerns – Chronic heart failure. As the population ages, the occurrence of heart failure (HF) is on the rise. In the US, almost 5 million people experience this condition with about 20%

mortality within 1 year and about 50% mortality within 5 years (4,5). Recent research using the rabbit as an animal model has illustrated that the CB plays a key role in CHF (6). Heart failure results in decreased blood flow in the common carotid artery with a resultant decrease in blood flow to the CB. The rabbits demonstrated an increase in CB neural output and renal sympathetic nerve activity. Decreased blood flow reduces sheer stress on the endothelial cells in the CB vasculature. This factor initiates a cascade of events that reduces nitric oxide synthase (nNOS) activity and NO in the CB. NO is a well-known attenuator of CB neural output (7,8). When an adenovirus was loaded with the gene for nNOS and injected into the CBs of the HF rabbits, CB neural output as well as SNS output were reduced (9). Modest exercise, which increases blood flow, also reduced CB neural output.

PERIOPERATIVE RELEVANCE

• Effect of sedation on the CB – Many drugs used in anesthesia depress regulation of breathing during acute hypoxia, among which are propofol, halogenated inhaled general anesthetics, and neuromuscular blocking agents. – In a recent study of human CBs, mechanisms behind this action were studied (5). And though many of the elements operating to depress ventilation and hypoxia-induced increases in CB neural output in animal models were the same in humans, not all of the implicated nonhuman elements could be found in human CBs. The authors speculate that in humans, propofol acts on the GABAA receptor in the CB, while inhaled halogenated anesthetics were found to target both K+ channels and neuronal acetylcholine receptors (nAChRs). Human CB nAChRs having the α3, α7, and β2 subunits would also be blocked by atracurium and vecuronium.

REFERENCES

1. DeCastro F. The discovery of sensory nature of the carotid bodies – Invited article. Adv Exptl Med Biol. 2009;648:1–18. 2. Nurse C. Neurotransmission and neuromodulation in the chemosensory carotid body. Auton Neurosc Bas Clin. 2005;120:1–9. 3. itzgerald RS, Shirahata M. Systemic responses elicited by stimulating the carotid body: Primary and secondary mechanisms. In: The Carotid Body Chemoreceptors, Ed. Gonzalez C. Heidelberg, Germany, Springer, 1997, pp. 171–191. 4. Paterson DJ. Targeting arterial chemoreceptor over-activity in heart failure with a gas. Circ Res. 2005;97:1–6. 5. Fagerlund M, Kahlin J, Ebberyd A, et al. The human carotid body – Expression of oxygen sensing and signaling genes of relevance for anesthesia. Anesthesiol. 2010;113:1270–1279. 6. Ding Y, Li YL, Schultz H. Role of blood flow in carotid body chemoreflex function in heart failure. J Physiol. 2011;589:245–257. 7. Wang ZZ, Stensaas L, Bredt D, et al. Mechanisms of carotid body inhibition. Adv Exptl Med Biol. 1994;360:229–235.

8. Fitzgerald RS, Shirahata M, Chang I, et al. L-arginine’s effect on the hypoxia-induced release of acetylcholine from the in vitro cat carotid body. Respir Physiol Neurobiol. 2005;147:11–17. 9. Schultz H, Li YL. Carotid body function in heart failure. Respir Physiol Neurobiol. 2007;157:171–185. 10. eath D, Smith P. Diseases of the human carotid body. London, Springer-Verlag, 1992, pp. 88–89. See Also (Topic, Algorithm, Electronic Media Element) • Congestive heart failure • Carotid endarterectomy • Carotid sinus

CLINICAL PEARLS

• Aging has an effect on the human CB: In three groups of adults with mean ages of 26, 52, and 79, the mean cross-sectional area of the CB (mm2) was 2.71, 3.12, and 4.42 respectively. But the mean percent of type I cell tissue was 45, 39, and 29. This suggests that the reflex responses to CB stimulation by hypoxia, hypercapnia, and hypoglycemia would become less as one ages. • A further consequence of aging is the diffuse infiltration of lymphocytes. In a group of 38 male and 37 female subjects, only 2 of 18 subjects under 50 years of age exhibited this phenomenon, while 32 of the 57 subjects greater than 50 years showed it. • The CB is affected by COPD. There is usually an accompanying right ventricular hypertrophy that is associated with alveolar hypoxia, hypercarbia, and muscularization of pulmonary arterioles. In emphysematous patients presenting without right ventricular hypertrophy, the mean weight of the combined CBs was 32.4 mg. In the presence of hypertrophy, the mean weight of the combined CBs was 56.2 mg. • In asthma, one might expect enlarged CBs due to the mild hypoxemia resulting from bronchospasm and mucus secretion. Stimulated CBs normally provoke contraction of airways smooth muscle. However, in asthmatic subjects who had undergone CB removal, the structures were not enlarged. But the proportion of sustentacular cells had doubled in the asthmatics compared to controls. And of the two types of type I (chief) cells, the dark type had increased from ∼28% of all type I cells in the normal CBs to 43% in the asthmatics. This suggests the possibility of an abnormal CB sensitivity (10). • A commonly used neuromuscular blocker during anesthesia, vecuronium has been shown in rats to decrease the neural output from the CB. It is believed that halothane, enflurane, and isoflurane prolong the effects of vecuronium, and this would suggest that the CB would remain hyporesponsive.

CAROTID ENDARTERECTOMY Jared Feinman, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION General

• Carotid endarterectomy (CEA) is an open surgical procedure to remove stenotic material from inside the carotid artery and improve perfusion to the brain. • An oblique incision is made along the anterior border of the sternocleidomastoid muscle and the platysma is divided on top of the carotid bifurcation; the omohyoid muscle will often also be divided. The carotid fascia is then incised and the common carotid artery (CCA) is exposed. • A soft, noncrushing clamp is applied to the internal carotid artery (ICA), and the external and CCA are subsequently clamped to provide a “bloodless" operating field. A shunt may be inserted above and below the clamps to maintain perfusion to the brain. • An arteriotomy is made in the CCA, extended past the occlusion in the ICA, and the plaque is removed. • Arterial closure is via a primary closure or patch, and the patient’s neurological status should be assessed before leaving the OR. • Embolic phenomena from the atheroma can be dislodged during clamping or plaque removal and travel up to the brain, causing infarction or TIAs. • The decision to proceed with a CEA versus medical management is based on the degree of stenosis, presence or absence of symptoms, and concomitant risk factors (1). – 70–99% stenosis/symptomatic: Proceed with CEA, shown to reduce 2-year stroke risk from 26% to 9% – 50–69% stenosis/symptomatic: Consider CEA, especially if male, >5-year life expectancy and surgical risk of stroke/death is <6% – <50% stenosis/symptomatic: Medical management – 60–99% stenosis/asymptomatic: Consider CEA, especially if age <75, life expectancy >5 years, and surgical stroke/death risk <3% – <50% stenosis/asymptomatic: Medical management • Endovascular carotid angioplasty and stenting are also available. It involves threading a catheter via a femoral arteriotomy, expanding a balloon (angioplasty), and inserting a stent to keep the artery patent. It carries an increased morbidity and mortality compared to CEA and higher rates of restenosis. Position

• Supine • Head extended and turned to the contralateral side • Shoulder roll facilitates exposure

Incision

Two inch incision over the left or right carotid Approximate Time 2–4 hours

EBL Expected 50–250 mL

Hospital Stay 2–3 days

Special Equipment for Surgery • Fluoroscopy, IV contrast dye • Vascular shunt

EPIDEMIOLOGY Incidence

• Stroke is the 3rd leading cause of death in the US. 700,000 strokes occur each year (of which 200,000 are recurrent). • 180,000 CEAs are performed in the US annually and an additional 30,000 carotid stents. Prevalence

Increases with age, male gender, hypertension, tobacco use, diabetes mellitus, hyperlipidemia, and homocysteinemia Morbidity

• Stroke (embolic or ischemic) in 5–7% of CEAs • Intracerebral hemorrhage in 0.6% of cases (60% are fatal) • Increased risk of perioperative myocardial infarction

Mortality

30-day postoperative mortality: 0.4%

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patient population with significant comorbidities. • Heparinization, and sometimes protamine reversal, is required. • Stroke is the most devastating complication; thus, preoperative, intraoperative (when possible), and postoperative neurological assessments are crucial.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Often asymptomatic, found in workup for other illness or carotid bruit heard on exam • May present as TIA or stroke

History

• Baseline neurological assessment; symptomatic patients will often have a history of stroke or TIAs. • Assessment for cerebral, coronary, renal, and/or peripheral vascular disease. • Assess stenosis in contralateral carotid artery, as this may impact collateral flow during surgery. Signs/Physical Exam Carotid bruit

MEDICATIONS

• Statins • Antiplatelet medications (aspirin, IIB/IIIA) • Antihypertensives (beta-blockers, calcium channel blockers, ACE inhibitors or ARBs, diuretics) DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Creatinine • PT/PTT, INR • Hemoglobin • Electrolytes if on diuretics, ACE inhibitors, renal insufficiency • Carotid Doppler ultrasound • Carotid angiography • Magnetic resonance angiography (MRA) • Computed tomography angiography (CTA)

CONCOMITANT ORGAN DYSFUNCTION • Coronary artery disease • Peripheral vascular disease • Chronic obstructive pulmonary disease • Renal insufficiency

TREATMENT PREOPERATIVE PREPARATION Premedications

• Perioperative beta-blockers may be considered; they have been shown to reduce cardiac morbidity and mortality in open repair; however, may increase the risk of stroke. Titrate to heart rate. • Perioperative statins may reduce hospital length of stay, postoperative complications, overall cost, and renal complications.

Special Concerns for Informed Consent

• Blood consent • If using regional anesthesia and sedation, discuss realistic sedation goals.

INTRAOPERATIVE CARE Choice of Anesthesia

• Regional: Superficial and/or deep cervical block – Pros: Allows for awake neurological exam and avoids hemodynamic shifts. Shunts are less commonly utilized. – Cons: Patient interference, neuroprotective qualities of anesthetic agents are lacking, and if the airway needs to be secured in the event of stroke, hemorrhage, seizure, agitation, or hypoxia, it must be done under less than optimal conditions. • General anesthesia (GA) with ETT – Pros: Secure airway, controlled surgical field, anesthetic meds may be neuroprotective. Reduced total procedural cost. – Cons: Hemodynamic changes, inability to perform an intraoperative neurological exam. • The General Anaesthesia Versus Local Anaesthesia for carotid surgery (GALA) trial showed no significant difference in stroke or death between GA and regional (2).

Monitors

• Arterial line; consider awake placement if hemodynamic instability can be detrimental. • Awake neurological exam (if possible) • Indirect neurological monitoring – Flow/pressure Stump pressure: Needle tip transducer inserted cephalad to the clamp, measuring back pressure in the ICA from collateral flow. Pressure goals vary by surgeon. Not very sensitive or specific for clinically significant ischemia. Transcranial Doppler (TCD) at the zygomatic arch to assess MCA blood flow via the Circle of Willis. Also has the ability to detect microemboli, but these are often not clinically significant. TCD is very operator dependent and its position may interfere with the surgical field. – Functional EEG: Raw and processed EEG has been used. Well-established EEG changes occur due to cerebral ischemia, but there are many limitations, including changes due to anesthesia, the inability to detect ischemia in deeper structures, and the need for specially trained personnel to interpret EEG. SSEP (somatosensory-evoked potential): Monitors transmission of signals from peripheral nerves to the sensory cortex (can identify ischemia in deeper structures). Amplitude is decreased by many anesthetic medications and requires trained personnel to operate. MEP (motor-evoked potential): Monitors transmission of signals from the motor cortex to peripheral nerves. More sensitive than SSEP to effects of anesthesia, muscle relaxation cannot be used, and specially trained personnel are required. – Consumption JVO2: Catheter placed in the jugular bulb to measure SpO2. Dependent on arterial oxygen saturation, cerebral blood flow (CBF) and CRMO2. Unclear yet if this is sensitive

or specific for ischemia, and no clear threshold level has been established.

Induction/Airway Management

• If EEG neuromonitoring is chosen, a baseline reading is performed prior to induction. • Slow, controlled induction is performed to avoid and treat significant hypotension that may exacerbate ischemia while achieving an adequate depth of anesthesia.

Maintenance

• Surgical traction on the carotid sinus can result in vagal stimulation, leading to hypotension and bradycardia. Releasing traction, or administration of glycopyrrolate/atropine may be required. Local anesthetic infiltration may abolish the response; however may last into the postoperative period. • Heparinization should be performed prior to cross-clamping of the carotid artery. • Placement of the cross-clamp often leads to hypertension via baroreceptor activity and increased sympathetic tone that may require treatment. It is important not to overtreat and cause hypotension, increasing the risk of ischemia. • Shunt placement to allow distal blood flow is based on surgeon preference. Some place a shunt routinely while others do so only if there is an indication (change in neuromonitoring indicating ischemia). • Elevation of the BP during cross-clamp time is often performed to maintain brain perfusion through collaterals and the contralateral carotid artery via the Circle of Willis. • Unclamping may be accompanied by reflex vasodilation and bradycardia.

Extubation/Emergence

• Avoid coughing and bucking and hypertension that could disrupt repair. • Neurologic exam should be performed post-op (an awake and oriented patient is beneficial).

POSTOPERATIVE CARE BED ACUITY

• Telemetry or intensive care unit (ICU) for frequent neurological exams and tight BP control. • Antiplatelet therapy (clopidogrel, aspirin), statins, and beta-blockers may need to be started or continued postoperatively. • Expanding neck hematoma may compromise airway.

ANALGESIA

• Pain is typically minimal, especially if regional anesthesia is used. • IV PCA if NPO, then NSAIDs and opioids.

COMPLICATIONS

• Stroke (embolic or ischemic) in 5–7% of CEAs • Hematoma in 5.5% of cases • Cerebral hyperperfusion syndrome (CHS) may lead to brain edema. Hypoperfusion is defined as a >100% increase in blood flow compared to preoperative values; it is due to impaired CBP autoregulation, hypertension, and ischemia-reperfusion injury. CHS can

present as a triad of ipsilateral headache, seizure, and focal neurological symptoms. • Seizures in 3% of cases • Cranial nerve injury (reported incidence ranges from 1% to 30%), often hypoglossal nerve • Intracerebral hemorrhage in 0.6% of cases (60% of these are fatal) • Recurrent stenosis • Increased risk of perioperative myocardial infarction

REFERENCES

1. Charturvedi S, Bruno A, Feasby T, et al. Carotid endarterectomy: An evidence-based review. Neurology. 2005;65:794–801.

2. GALA trial collaborative group. General anaesthesia versus local anaesthesia for carotid surgery (GALA): A multicentre, randomized control trial. Lancet. 2008;372:2132–2142. 3. Goldstein LB, McCrory DC, Landsman PB, et al. Multicenter review of preoperative risk factors for carotid endarterectomy in patients with ipsilateral symptoms. Stroke. 1994;25:1116–1121.

ADDITIONAL READING

• NASCET trial group. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325:445–453. • ESCT trial group. Randomized trial of endarterectomy for recently symptomatic carotid stenosis. Lancet. 1998;351:1379–1387. See Also (Topic, Algorithm, Electronic Media Element)

• Electroencephalogram (EEG) • Somatosensory- and motor-evoked potentials

CODES ICD9 433.10 Occlusion and stenosis of carotid artery without mention of cerebral infarction ICD10 • I65.21 Occlusion and stenosis of right carotid artery • I65.22 Occlusion and stenosis of left carotid artery • I65.29 Occlusion and stenosis of unspecified carotid artery

CLINICAL PEARLS

• Beta-blockers and statins should be continued perioperatively; some evidence to suggest that initiation of therapy confers a survival benefit and discontinuation may increase morbidity or mortality. • GA or regional anesthesia has equivalent outcome data. • Risk of embolic or ischemic stroke due to CEA is significant, and serial neurological exams

must be documented.

CAROTID SINUS

Brooke Albright, MD, MAJ, MC

BASICS DESCRIPTION

The carotid sinus is a baroreceptor that is located at the bifurcation of the internal and external carotid artery. It is involved in blood pressure and heart rate homeostasis. PHYSIOLOGY PRINCIPLES

• The carotid sinus reflex describes baroreceptor-mediated hemodynamic suppression to high arterial wall tensions resulting in hypotension and bradycardia. • When a rise in arterial pressure stretches the baroreceptors, sodium channels are activated and afferent signals (via the glossopharyngeal nerve) travel to central nuclei, including the nucleus tractus solitarius. From there, long preganglionic efferent fibers via the vagus nerve propagate to the heart and synapse on postganglionic neurons in myocardial tissue. These postganglionic neurons directly stimulate pacemaker cells and conducting pathways to slow down the heart. The reflex can be elicited manually by external carotid massage. • Bronchoconstriction is another possible side effect of direct stimulation of the carotid sinus.

ANATOMY

The carotid sinus is located within the bifurcation of the internal and external carotid arteries.

FIGURE 1. Carotid Sinus. The baroreceptor is located at the bifurcation of the internal and external carotid arteries. It

sends afferent input to the central nuclei via the glossopharyngeal nerve and efferent input travels to the heart via the vagus nerve. Illustration by Brooke Albright, MD

DISEASE/PATHOPHYSIOLOGY

• Atheromatous plaques located within the region of the carotid sinus impair the sensitivity of the baroreceptor stretch receptors. Once these plaques are removed, such as in carotid endarterectomy surgery, an exaggerated response to changes in BP and cardiac rhythms may be encountered (1). • Increased age, hypertension, and diabetes can all lead to impaired cardio-vagal reflex responses and increased cardiovascular morbidity (1). • In the transplanted heart, vagus nerve innervation is severed. Parasympathetic stimulation via carotid massage, arterial wall stretch of the carotid sinus, and the Valsalva maneuver are not effective in slowing the heart rate. Indirect acting medications are also ineffective in the denervated heart. • Carotid sinus syndrome (CSS) is a disease characterized by nausea, vomiting, dizziness, syncope, severe hypotension, and asystole due to hypersensitivity of the carotid sinus. It is a recognized complication following carotid endarterectomy surgery in some patients. Treatment may require a pacemaker, glossopharyngeal nerve block/ablation, or surgical denervation of the glossopharyngeal nerve at the level of the carotid bifurcation (2). If a regional nerve block is selected for therapy, an electrical stimulating needle is passed

anterior to the styloid process until the patient complains of vague sensations in the regions supplied by the nerve, such as the external ear or pharynx. If performance of block successfully reduces symptoms after testing with carotid massage, then the nerve is ablated with ethanol. • New technology development and testing related to stimulation of the carotid sinus is underway for the treatment of drug-resistant hypertension. The Rheos Multicenter Feasibility Trial is currently investigating an implantable pulse generator and bilateral perivascular carotid sinus leads that electrically activate the afferent limbs of the carotid sinus baroreflex and reduce overall sympathetic vascular tone over time. FDA-approved phase II clinical trials have been promising (3).

PERIOPERATIVE RELEVANCE

• Carotid artery stenting can lead to severe bradycardia and cardiac rhythm disturbances during balloon angioplasty. Different techniques have been utilized with varying degrees of success to prevent episodes of bradycardia, including intravenous injection of atropine, and injection of local anesthetic into the carotid sinus prior to dilation. Infiltration of the carotid sinus with 5 mL of 1% lidocaine 3 minutes before dilation allowed stable hemodynamics and did not lead to bradycardia in one study (4). • Carotid endarterectomy surgery may lead to deterioration of baroreceptor function at the point when the atheromatous plaque is removed, although the exact mechanism by which this happens is unclear. – Some theories suggest that removal of the plaque results in denervation of the baroreceptor nerve fibers within the arterial wall, which could result in sympathomimetic electrocardiographic changes and hypertension. – If carotid afferent fibers are maintained intact, then postoperative hypotension is possible due to hyperactivity of the newly exposed carotid sinus to the increased perceived BP. • Prophylactic administration of intravenous atropine is advocated by some anaesthetists whenever manipulation of the carotid sinus is expected. • Volatile anesthetics have been shown to depress baroreflex control of heart rate in a concentration-dependant manner and continue to exert depressive effects after emergence from general anesthesia (5). • Prolonged nitroprusside infusion as well as sevoflurane anesthesia can lead to a shift in the baroreceptor reflex resting set point such that perturbations of the carotid sinus result in smaller fluctuations of hemodynamics (6). • Surgery for CSS may include “adventitial stripping,” whereby the proximal carotid artery is opened and the sinus is denervated over an area of at least 3 cm. Postoperative monitoring is mandatory since wide variations in heart rate and BP can occur (6).

REFERENCES

1. The parasympathetic nervous system is fully functional at birth in the neonate, including the baroreceptor reflex. In contrast, the sympathetic nervous system is not complete until 4–6 months of age. As a result, certain noxious stimuli may cause bradycardia in neonates. During general anesthesia, the responsiveness of the baroreceptor reflex may be reduced by volatile anesthetics.

2. Gianaros PJ, Jennings JR, Olafsson GB, et al. Greater intima-media thickness in the carotid bulb is associated with reduced baroreflex sensitivity. Am J Hypertens. 2002;15(6):486– 491. 3. Toorop RJ, Scheltinga MR, Moll FL, et al. Anatomy of the carotid sinus nerve and surgical implications in carotid sinus syndrome. J Vasc Surg. 2009;50(1):177–182.

4. Tordoir J, Scheffers I, Schmidli J, et al. An implantable carotid sinus baroreflex activating system: Surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension. Eur J Vasc Endovasc Surg. 2007;33(4):414–421. 5. Mourikis D, Chatoupis K, Katsenis K, et al. Percutaneous injection of lidocaine within the carotid body area in carotid artery stenting: An “old-new” technique. Cardiovasc Intervent Radiol. 2008;31(4):709–712. 6. Umehara S, Tanaka M, Nishikawa T. Effects of sevoflurane anesthesia on carotid-cardiac baroreflex responses in humans. Anesth Analg. 2006;102(1):38–44. 7. Toorop RJ, Scheltinga MR, Moll FL. Adventitial stripping for carotid sinus syndrome. Ann Vasc Surg. 2009;23(4):538–547.

ADDITIONAL READING

• Hines, R, Marschall K. Stoelting’s Anesthesia and Co-Existing Disease, 5th Ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2008:252.

See Also (Topic, Algorithm, Electronic Media Element) • Carotid body • Carotid endarterectomy • Heart transplant

CLINICAL PEARLS

• Increased arterial wall tension or external pressure on the carotid sinus (i.e., carotid massage) induces hypotension and bradycardia via a baroreceptor-mediated reflex. • Atropine can be given to attenuate the effects of the carotid sinus baroreflex when manipulation is anticipated in normal hearts. • The transplanted heart is parasympathetically denervated; therefore, atropine and baroreceptor-mediated reflexes are ineffective.

CATARACT EXTRACTION Matthew C. Gertsch, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION General

• A cataract is an opacity in the lens of the eye that can cause partial or total blindness. It results from changes to the crystalline lens fibers that can accompany aging and disease processes: Increased density, clumping, and formation of opacities. • Eye drops are administered to dilate the pupils. The surgical area is exposed with a lid speculum that prevents blinking. • An incision in the anterior capsule is made to gain access. The cataract is emulsified (broken up) either by phacofracture or phacoemulsification (phaco) (1). – Phacofracture is an extracapsular cataract extraction (ECCE) technique. It is utilized more commonly in developing countries, for very hard cataracts, and for weak epithelial tissue in the cornea. After an incision is made, a circular tear in the front of the lens capsule is made. Instruments are inserted to remove the lens intact or be mechanically broken up (and suctioned). An air bubble or viscoelastic material may be injected into the empty lens capsule to maintain its shape during the lens insertion. – Phaco is the preferred method for extraction. It involves the insertion of a tiny, hollowed instrument that utilizes ultrasonic vibrations (high frequency 40,000 Hz) to emulsify the cataract. The same tip may be utilized to suction out the lens. • An intraocular lens implant is inserted to replace the cloudy lens that was removed. A variety of options are available that are beyond the scope of this chapter. • If viscoelastic material is injected, it is typically removed after the lens is in place. Position Supine

Incision

• Anterior capsulotomy • Phaco involves a small, 2–3 mm incision that is typically self-sealing (without suturing). • ECCE requires a larger, 5–12 mm incision that requires suturing; may be performed via a microincision technique (<1.5 mm).

Approximate Time 15–60 minutes EBL Expected Minimal

Hospital Stay

Outpatient procedure

Special Equipment for Surgery • Microscope • Intraocular lens implant • Ultrasonic machine

EPIDEMIOLOGY Incidence

• US in 2005: Approximately 2,790,000 cataract surgeries were performed (2). • US: 1 in 50 will have a cataract removed (2). • The number of people in the US affected by cataracts is estimated to rise to 30.1 million people in the next 20 years (an increase of 50%) (2). • Cataracts are responsible for blindness in 19,000,000 people worldwide (50% of all cases of blindness) (3). • Women are almost 40% more likely to develop cataracts than men (3).

Prevalence

• Increases with age • It is estimated that 20.5 million (17.2%) of Americans aged 40 years and above have a cataract in either eye (3). Morbidity

Surgical complications include posterior capsular tear, retinal detachment, infection, and glaucoma. Mortality

Negligible

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Although this is a quick, simple, and hemodynamically stable procedure that can be performed without sedation, the anesthesia provider may be asked to provide care due to significant comorbidities (Parkinson’s disease, dementia, pulmonary cripples, uncontrolled hypertension, anxiety, or other mental disorders), pediatric cases, or when a retrobulbar block is utilized. • The need for a cardiac workup may arise based on the patient’s history, signs and symptoms, or EKG. It must be weighed against the minimal hemodynamic effects and American Heart Association (AHA) “low-risk” surgical procedure classification, on an individual basis. Patients with acute ischemia should clearly be delayed for cardiac treatment; however, those with nonspecific but suggestive symptoms can pose a conundrum to the anesthesia care provider. • The surgical location precludes easy access to the airway. Supplemental oxygen via nasal cannula is advisable, and all sedatives should be carefully titrated.

PREOPERATIVE ASSESSMENT SYMPTOMS

Blurry vision History

Patients requiring anesthesia often have significant comorbidities, which need to be carefully assessed and evaluated. Signs/Physical Exam

• Visual deficits • Check for signs and symptoms of cardiac and pulmonary decompensation. • Attention to positioning issues in patients with severe scoliosis and orthopnea.

MEDICATIONS

• Alpha blockers may result in intraoperative floppy iris syndrome. • Topical steroid use; has very minimal systemic absorption.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• No routine screening tests have been shown to improve outcomes. Tests are based on the patient’s other comorbidities. • Although 12-lead EKGs are commonly ordered on patients within this age group, delaying the procedure to attain the test may not be warranted. It is often deemed appropriate, however, in patients with a pacemaker or defibrillator, significant cardiac history, or signs and symptoms of acute ischemia.

CONCOMITANT ORGAN DYSFUNCTION • Coronary artery disease • Pulmonary disease • Dementia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis may be warranted, but may cause confusion, dysphoria, and prolonged sedation in the elderly. If administered, the use of midazolam, a short-acting agent, is preferred. • Narcotic, as needed, to assist with lying flat. Again, the use of a short-acting agent, such as fentanyl or alfentanil, is preferred. • Supplemental oxygen

Special Concerns for Informed Consent

If performed as a monitored anesthesia care (MAC) technique, patient and family should be made aware of reasonable sedation goals and the potential for some recall of intraoperative events. Antibiotics/Common Organisms Topical

INTRAOPERATIVE CARE Choice of Anesthesia

• MAC in conjunction with topical local anesthetic or retrobulbar block is most commonly provided. It avoids unnecessary hemodynamic swings, airway instrumentation, and postoperative cognitive dysfunction that may be associated with a general anesthetic in this patient population. – Topical anesthesia provides a safe, comfortable, expedient, and cost-effective mechanism of pain relief. It avoids the risks of local anesthetic systemic toxicity or total spinal. – Retrobulbar block. Provides anesthesia as well as akinesia (prevents movement). It is typically performed by the ophthalmologist with a needle inserted in the inferior orbital rim and advanced at a caudal angle to a depth of ∼1.5–2 cm. After careful aspiration, 2–3 mL of local anesthetic is injected. – Peribulbar block. Typically performed by the ophthalmologist through the lower lid. • General anesthesia is considered in certain situations such as in pediatrics, demented, or violent patients.

Monitors

Standard ASA monitors

Induction/Airway Management

• MAC – Supplemental oxygen; typically with a nasal cannula to avoid invasion of the surgical field. – Judicious titration of anxiolytics, sedatives, and/or opioids (potential for compounded sedative or respiratory depressant effects). – Backup airway equipment should be available. • General anesthesia – Although a laryngeal mask airway may be utilized, it is less secure than an endotracheal tube (shared space and head of bed position) and may not be appropriate. – Induction may result in wide swings in blood pressure; a slow, controlled induction should be performed. – Succinylcholine may be contraindicated; consider not utilizing nondepolarizing neuromuscular blocking drugs if the procedure is expected to be quick (duration of action may preclude reversibility in a timely manner).

Maintenance

• MAC – Agitation may be one of the first signs of hypoxia or hypercarbia. Be cautious about

“giving more” before ruling out hypoxia and hypercarbia (especially in a patient that was previously cooperative). – Sedation should be titrated to patient comfort and the ability to communicate. • General anesthesia – Volatile or total intravenous anesthetic – Minimal opioid administration, as a local anesthetic block is commonly performed to reduce postoperative pain.

Extubation/Emergence

• MAC – Reorient patient as needed • General anesthesia – Consider deep extubation to avoid coughing and bucking. However, in the event of difficult mask ventilation, this may not be appropriate. Airway should trump all other considerations. Consider intravenous lidocaine 2–3 minutes prior to extubation (or topical lidocaine at the time of intubation).

POSTOPERATIVE CARE BED ACUITY

• Outpatient surgery and discharge criteria should be met. • Patients should not be allowed to drive themselves home.

ANALGESIA

Often not needed; consider acetaminophen COMPLICATIONS

• Puncture site hematoma • Retrobulbar blocks: Retrobulbar hemorrhage, local anesthetic systemic toxicity (the proximity to the brain decreases the toxic dose required), globe perforation, optic nerve damage, and total spinal. • Peribulbar blocks: May need to be repeated, as they have a longer time to onset.

REFERENCES

1. Thomas R, Kuriakose T. Surgical techniques for a good outcome in cataract surgery: Personal perspectives. J Comm Eye Health. 2000;13(35):38–39. 2. National Eye Institute (NEI). Are you at risk for cataract? Publication No 94-3463. 3. Congdon N, Vingerling JR, Klein BE, et al. Prevalence of cataract and pseudophakia/aphakia among adults in the United States. Arch Ophthalmol. 2004;122(4):487–494.

ADDITIONAL READING

• Emmanuel N, Philippe C. Anesthesia for cataract surgery. Drugs Aging. 2010;27(1):21–38.

See Also (Topic, Algorithm, Electronic Media Element) • Oculocardiac reflex • Total spinal • Local anesthetic systemic toxicity

CODES ICD9

366.9 Unspecified cataract ICD10

H26.9 Unspecified cataract

CLINICAL PEARLS

• Anesthesia providers are often asked to provide care for patients with significant comorbidities. The need for efficiency and speed, combined with the low cardiac risk of the procedure, should not preclude proper patient management. • General anesthesia may be required in certain situations, such as in pediatric, demented, or violent patients, but this carries an increased risk. • MAC must implement judicious titration of medications that can cause respiratory depression; the patient’s head is shared with the surgeon and makes easy access somewhat challenging.

CAUDAL EPIDURALS Peter K. Yi, MD

BASICS DESCRIPTION

• Caudal epidurals can be used as an alternate form of intraoperative or postoperative pain control, as well as provide intraoperative muscle relaxation and reduce anesthetic requirements. • Caudal epidurals are performed for: – Surgical procedures with sacral and lower lumbar innervation Inguinal and femoral herniorrhaphy Cystoscopy and urethral surgery Hemorrhoidectomy and anal dilation Gynecologic procedures Surgery on the penis or scrotum – Pediatric patients for the above-mentioned surgical procedures, as well as for desired lumbar and thoracic epidural coverage (catheter can be threaded for single shot and removed, or remain indwelling). Entry in the epidural space at this level, as opposed to higher in the spine, has a decreased incidence of accidental subarachnoid injection since children have a lower lying dural sac. Additionally, the anatomy is more easily appreciated; the sacral cornua and ligaments thicken with age. – Chronic back pain with a radicular component. The injection of corticosteroids and local anesthetics is usually performed with fluoroscopic guidance. In general, caudals are not done for complex regional pain syndrome (CRPS) or cancer pain. – Patients with prior lumbar spinal surgery that would benefit from an epidural injection; a catheter can be threaded to the appropriate level to increase the likelihood of medications reaching the targeted nerves. PHYSIOLOGY PRINCIPLES

Injectate. Because caudal epidurals are placed at the terminus of the spinal canal, an increased volume is used to achieve appropriate anesthesia or analgesia. In addition to volume, the patient’s age and weight can affect the epidural spread of medications. • Pediatrics. Volumes of 0.7–1.0 mL/kg have been suggested to reach an analgesic level of ∼T10. • Adults. Volumes of 10–25 mL are typically injected. • Caution must be taken with the amount of volume used since loculation of the injectate can occur and thus compromise blood supply to the spinal cord. This phenomenon can be seen in patients who have scar tissue from previous spinal surgery. ANATOMY

• Performing a caudal epidural requires understanding of the sacral anatomy. The anatomy is

typically easier to palpate in children; hence it is more readily used in this population. – The sacrum is a fusion of the five sacral vertebral bodies. – The sacral hiatus is the failure of the laminae of S5 and part of S4 to fuse together. It takes on a variable form among individuals but is usually an inverted “V” shape. – The sacrococcygeal ligament is the extension of the ligamentum flavum. It overlies the sacral hiatus between the sacral cornua. • The dural sac terminates around S3–4 in children and around S1–2 in adults, (usually at the level of the posterior superior iliac spine). The spinal cord, however, ends around L3 in infants and at L1–L2 in adults. • Epidural fat is more fluid in children and thus can allow an increased range of spread. In adults, the fat is more densely packed and limits the spread of medications.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Chronic back pain. Caudal epidurals have been shown to have moderate levels of efficacy in appropriately selected patients (2). Corticosteroids reduce inflammation and inhibit the further release of pro-inflammatory mediators. • Potential complications of caudal epidurals include: – Infection (epidural abscess, meningitis) – Bleeding (epidural hematoma) – Dural puncture and associated postdural puncture headache – Patchy spread of local anesthetic – Nerve injury – Local anesthetic systemic toxicity (increased vasculature compared to lumbar or thoracic epidural spaces) from vascular absorption. – Inadvertent subdural or intravascular injection – Pneumocephalus, air embolism – Back pain – Sheared or knotted epidural catheters

PERIOPERATIVE RELEVANCE

• Positioning – Children: Commonly placed in the lateral position after induction (or sedation for MAC cases) with the knees pulled towards the abdomen – Adults: Can be performed in the lateral or prone position while the patient is awake or mildly sedated • Landmarks – Children: The sacral hiatus and cornu are typically located with palpation – Adults: The sacral cornua and ligaments thicken with age and are not readily identified by palpation. After identifying the posterior superior iliac spine, an imaginary line is drawn towards the coccyx to approximate the sacral hiatus. These lines form an equilateral triangle with the sacral hiatus located at the bottom corner.

FIGURE 1. Landmark Identification. The sacral hiatus is located at the bottom corner of an equilateral triangle formed by lines from the posterior iliac spines.

• Preparation. As with any procedure, appropriate prep and drape as well as sterile technique should be maintained. • Needles – Children: Single shot local anesthetic and/or opioid administration is commonly performed with a 20 or 22 gauge needle. Appropriately sized epidural needles are utilized when placement of an indwelling catheter is desired. – Adults: The skin and subcutaneous tissue of the sacral hiatus can be infiltrated with 1–2 mL of 1% lidocaine prior to insertion. A Tuohy needle is utilized for catheter placement. A 20 or 22 gauge needle is typically used for steroid/local anesthetic injection for chronic pain procedures • Needle insertion: A decrease in resistance should be felt as the needle passes into the caudal canal; it is advanced until bone is contacted. The needle is then withdrawn slightly and redirected at an angle more parallel to the skin. Another loss of resistance is encountered as the needle passes through the sacrococcygeal ligament and is then advanced another 1–2 cm. • Confirming proper placement in adults: – A syringe is attached to the needle and aspirated. If aspiration is negative for "heme" and cerebrospinal fluid, a test dose can be administered (typically ~3 mL of lidocaine 1.5% with 1:200,000 epinephrine). Look for signs of intrathecal (sensory/motor block within minutes) and intravascular (increased heart rate, palpitations, hypertension) injection. – The Whoosh test involves injection of 2 mL of air through the needle while listening with a stethoscope placed at the thoracolumbar spine. If a “whoosh" is heard, this can indicate that the needle is in the caudal epidural space (5). • Local anesthetics – Bupivacaine 0.25% or ropivacaine 0.2% can be used and provides analgesia for 6–8 hours. – As previously mentioned, volumes are dependent on the level of anesthesia/analgesia

required for a particular case. The following can also be used as general guidelines for dosing local anesthetics in adults: Sacral dermatomes: 0.5 mL/kg Sacral and lumbar dermatomes: 1.0 mL/kg Midthoracic dermatomes: 1.25 mL/kg (increased risk of rostral spread) • Adjuncts. The addition of epinephrine can prolong the duration of action (vasoconstriction decreases systemic absorption and increases the duration that the local anesthetic will remain in the epidural space). • Indwelling catheters are placed for continuous infusion or repeat bolusing. Care should be taken since securing and preventing catheter migration can be difficult in the sacral region. Catheters may also be utilized when local anesthetic delivery to a higher level is desired, but where placement of an intralaminar or transforaminal epidural injection may be difficult. However, this is usually limited due to scar formation from prior instrumentation. The spread and distribution of the medication can be tracked with fluoroscopy after 1–2 mL of contrast dye is injected through the catheter

REFERENCES

1. ggarwal A, Kaur H, Batra YK, et al. Anatomic consideration of caudal epidural space: A cadaver study. Clin Anat. 2009;22(6):730–737. 2. bdi S, Datta S, Trescot AM, et al. Epidural steroids in the management of chronic spinal pain: a systematic review. Pain Physician. 2007;10(1):185–212. 3. Armitage EN. Regional anaesthesia in paediatrics. Clin Anesthesiol. 1985;3:553–558.

4. Barham G, Hilton A. Caudal epidurals: The accuracy of blind needle placement and the value of a confirmatory epidurogram. Eur Spine J. 2010;19(9):1479–1483. 5. Eastwood D, Williams C, Buchan I. Caudal epidurals: The whoosh test. Anaesthesia. 1998;53(3):305–307. 6. Manchikanti L, Pampati V, Boswell MV, et al. Analysis of the growth of epidural injections and costs in the Medicare population: A comparative evaluation of 1997, 2002, and 2006 data. Pain Physician. 2010;13(3):199–212. 7. Thomas ML, Roebuck D, Yule C, et al. The effect of volume of local anesthetic on the anatomic spread of caudal block in children aged 1–7 years. Paediatric Anaesthesia. 2010;20(11):1017–1021. 8. Rathmell J. Atlas of Image Guided Intervention in Regional Anesthesia and Pain Medicine. Philadelphia: Lippincott Williams Wilkins; 2006. • American Society of Anesthesiologists Taskforce on Pain Management. Practice guidelines for chronic pain management: An updated report by the American Society of Anesthesiologists Task Force on Chronic Pain Management and the American Society of Regional Anesthesia and Pain Medicine. Anesthesiology. 2010;112(4):810–833. See Also (Topic, Algorithm, Electronic Media Element)

• Epidural • Postdural puncture headache

• Local anesthetic toxicity

CLINICAL PEARLS

• Single shot caudal epidurals can be useful in children undergoing surgeries below the umbilicus (e.g., inguinal or genital procedures); it can decrease the amount of general anesthesia to be used. This can be significantly beneficial in neonates where volatile agents can cause postoperative apnea. • For patients on anticoagulation therapy, the general precautions apply when performing a caudal epidural as with any other neuraxial procedure.

CELIAC PLEXUS BLOCK Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Celiac plexus block (CPB) is commonly used for blockade or neurolysis of visceral afferent pain fibers to treat upper abdominal pain. The most common indication is pancreatic cancer; however, it is also used for other abdominal cancers and occasionally for benign conditions such as acute or chronic pancreatitis. • In one study, good to complete pain relief at 1 week reached 85%; continued relief at 3 months was seen in 50–90% of these patients (1)[B]. Duration of the neurolytic block can be hindered by aggressive tumors that invade the peritoneum and surrounding organs, as well as by regeneration of new pain pathways. PHYSIOLOGY PRINCIPLES

• The celiac plexus is an aggregate of ganglia and a dense network of nerve fibers that innervates most of the digestive tract. • It contains autonomic efferent nerves that innervate the upper abdominal viscera and visceral afferent fibers from the distal esophagus to transverse colon. Afferent fibers travel along sympathetic nerves.

ANATOMY

• Located in the abdomen at approximately the L1 level, anterior to the aorta, and below the crus of the diaphragm. • Surrounds the celiac artery and root of the superior mesenteric artery. • The plexus has several ganglia components that have the appearance of lymph nodes. The celiac ganglia comprise the “middle” of the plexus, and vary in number (1–5), size (0.5–4.5 cm), and position relative to the vertebral column (bottom of T12 to middle of L2). The upper portions of the celiac ganglia are joined by the greater splanchnic nerves (sympathetic chains) after they pierce through the diaphragmatic crura, while the lower portions receive the lesser splanchnic nerves. In addition to sympathetic fibers, it also receives some fibers from the right vagal nerve (parasympathetic). • Secondary plexuses arise from or connect with the celiac plexus: Phrenic, hepatic, lineal, superior gastric, suprarenal, renal, superior mesenteric, abdominal aortic, inferior mesenteric.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Pancreatic cancer remains the most common indication for CPB. Tumors of the pancreas can cause pain by invasion or stretching of nerves, involvement of viscera or organs, and blockage of the pancreatic ducts (2)[B]. Neurolysis has been shown to be more effective when the tumor involves the head of the pancreas. Patients with advanced tumor

proliferation and metastasis showed less favorable results. The limited therapeutic options, short life expectancy, and opioid limitations of pancreatic cancer make CPB a potentially effective component of a multimodal treatment regimen. • Other abdominal malignances such as gastric, esophageal, colorectal, and gallbladder cancer, as well as liver metastasis and cholangiocarcinoma (3)[A] may be indications for a CPB. As with pancreatic cancer, new pain pathways, or growing tumor, can limit long-term efficacy. • Chronic and acute pancreatitis. CPBs are controversial for this indication; opponents state that the lack of long-term pain reduction and potential adverse effects limit its use. Advocates, however, assert that the improvement in quality of life (amelioration of food intolerance, weight loss, and opioid use), even if temporary, justifies the procedure (4). • Complications – Hypotension. Sympatholysis of the splanchnic vasculature causes pooling of blood in this large capacitance, vascular bed (common and transient). Prophylaxis with prehydration (500–1000 mL crystalloid), appropriate monitoring (during and after the procedure), and treatment can alleviate the effects and consequences. Elderly, debilitated, and acutely or chronically dehydrated patients may be at a greater risk for hypotension (5)[A]. – Nerve injury/paraplegia. May occur from the spread of neurolytic agent to somatic nerves (6)[B], spinal cord ischemia due to radicular artery spasm, or needle injury to the spinal cord. Manifestations are multitudinous, transient and permanent, and of varying severity (loss of sensation over anterior abdominal wall to paraplegia). – Pneumothorax can occur in up to 1% of CPB blocks secondary to passing the percutaneous needle through the pleura of the lungs. A high index of suspicion should exist in the setting of reduced pulse oximetry, dyspnea, or tachypnea. – Diarrhea results from unopposed parasympathetic activity (sympathetic block). Up to 60% of patients encounter self-limited diarrhea for 36–48 hours (5)[B]. – Failed block from poor placement of the needle, alternative pain pathways, anatomic variations, insufficient volume of neurolytic agent, or the inability to inject the agent secondary to tumor or scar tissue encasement of the aorta in the region of the celiac plexus. Additionally, distorted anatomical relationships (ascites, organomegaly, tumor bulk, obesity), postradiation changes, postsurgical changes, peritoneal seeding, and surgical clip interference may also reduce successful neurolysis. Long-term failure may be seen when local extension of the tumor involves structures with other pain fiber pathways. PERIOPERATIVE RELEVANCE

• Anticoagulation must be discontinued with documentation of normal PT/INR and PTT if suspicion of clotting dysfunction exists. • Monitoring. Standard ASA monitoring. If sedative or opioid administration is given, supplemental oxygen such as a nasal cannula or facemask should be applied. Avoid oversedation in the prone position; oversedation also prevents assessing the effectiveness of the local anesthetic injection prior to neurolysis. • Imaging. Radiologic guidance is considered the standard of care to identify the needle tip location as it is advanced, as well as the final needle position with radiocontrast before injection of neurolytic material; most frequently performed with x-ray, fluoroscopy, or CT

assistance. • Local anesthetic. Prior to neurolysis with permanent agents, a local anesthetic block is performed for diagnostic and prognostic purposes to confirm that the pain is part of a viscerally mediated pathway. Most practitioners perform this in two stages on the same day, without moving the confirmed needle placement. Both lidocaine 0.5–2% (10–15 mL) and bupivacaine 0.125–0.25% (10–15 mL) can be used. • Posterior approach. There are two described techniques: The deep splanchnic nerve block (SNB) or true CPB. The clinical effect and potential complications between the two techniques are virtually indistinguishable. Although they both utilize percutaneous needles introduced at the T12 level, the needle tip in relation to the diaphragmatic crura differs (retrocrural for SNB and antecrural for CPB). The decision between the two techniques may depend on the indication as well as potential for complications. The CPB may be more useful for visceral abdominal pain secondary to pancreatic masses where the celiac plexus anatomy may be distorted; it also has the benefit of being unilateral, requiring less neurolytic agent, and possibly a more contained spread in the preaortic area. The SNB may predispose to complications including paraplegia, resulting from diffusion of neurolytic agents to the nerve roots, pneumothorax, or damage to the liver or kidney. – Retrocrural SNB. After identifying the L1 spinous process, bilaterally mark points 7–8 cm from the midline and place a skin wheal with local anesthetic. Begin on one side by inserting a 20 or 22 g 10–15 cm needle at a 45–60% angle from the table. The needle tip should be advanced to a final position anterior to the body of L1. In the anteroposterior view, the needle tip should be close to the midline, overlying the same vertebral body. This is repeated on the other side. – Antecrural SNB (CPB). The antecrural, or true CPB, involves unilateral needle placement anterior to the diaphragmatic crura. The right side may be preferred to avoid the aorta. After identifying the L1 spinous process, create a skin wheal on one side 5–6 cm from the midline. A 20 or 22 g 10–15 cm needle is inserted at a 45–60% angle from the table. The needle tip should be advanced to a final needle position that is anterior to the vertebral body, typically 10–13 cm of needle insertion. – Aspiration is performed prior to injection of radiocontrast, local anesthetic, or neurolytic agent in order to rule out CSF, urine, and blood. • Anterior approach. Typically performed by surgeons when performing open splanchnicectomies; or percutaneously with CT, MRI, and ultrasound imaging modalities using “skinny needles.” Advocates of the anterior approach cite a low complication rate, avoidance of the prone position (recent abdominal surgery, pain, pulmonary compromise from ascites, etc.), and one puncture (less discomfort, procedure time, and volume of neurolytic agent). Potential disadvantages include damage to the visceral organs that the needle passes through, peritonitis and intra-abdominal abscess, hemorrhage and fistula formation. • Neurolytic agents. The volume injected depends on the localization of the needle and ease of flow in the injected area. The volume of injectate is usually 25 mL through each needle, because the needle tip is placed directly into the plexus; the anterior approach typically uses a smaller injectate of 15–30 mL. The two available options are alcohol and phenol; studies have not clearly delineated a benefit with one over the other.

– Alcohol. Mechanism of action involves the extraction of cholesterol and phospholipid from the neural membrane and the precipitation of lipoproteins and mucoproteins. Concentrations range from 50% to 100%. Benefits include the possibility of more intense nerve destruction compared to phenol. Drawbacks include the potential for severe, transient pain on injection; the addition of local anesthetic can reduce the discomfort. – Phenol. Mechanism of action involves protein coagulation and necrosis of the neural structures. Concentrations range from 6 to 10%. Benefits include less pain with injection (has an immediate local anesthetic effect). Drawbacks include a slightly slower onset of action, less efficacy, shorter duration, and increased viscosity that makes it difficult to inject (6% is often preferred to the 10%). • Radiofrequency lesioning. A “neurodestructive” procedure that lesions the nerve plexus with temperatures that exceed 45°C. Advocates cite the benefit of a circumscribed and controlled lesion, compared to neurolysis. The proximal and distal spread of the lesion beyond the uninsulated tip of the probe is only 1 mm, with the cross-sectional lesion diameter 5–6 mm. There is little or no possibility of nerve root damage or destructive damage of the epidural and subarachnoid structures. Sensory and motor stimulation are often performed, in order to ensure that there is no break in the insulation.

GRAPHS/FIGURES

REFERENCES

1. Firdousi FH, Sharma D, Raina VK. Palliation of celiac plexus block for upper abdominal visceral cancer pain. Trop Doct. 2002;32(4):224–226. 2. Nakagawa T, Mori K, Nakano T, et al. Perineural invasion of carcinoma of the pancreas and biliary tract. Br J Surg. 1993;80(5):619–621. 3. Eisesnberg E, Carr DB, Chalmers TC. Neurolytic celiac plexus block in varying locations of

pancreatic cancer: Influence of pain relief. Anesthesiology. 2000;92(2):347054.

4. Mercadante S. Celiac plexus block: A reappraisal. Reg Anesth Pain Med. 1998;23(1):37–48.

5. Raj PP. Celiac plexus/splanchnic nerve blocks. Tech Reg Anesth Pain Manag. 2001;5(3):102–115. 6. Wong GY, Brown DL. Celiac plexus block for cancer pain. Tech Reg Anesth Pain Manage. 1997;1(1):18–26. 7. Romanelli DF, Beckmann CF, Heiss FW. Celiac plexus block: Efficacy and safety of the anterior approach. Am J Roentigenol. 1993;160(3):497–500.

8. att RB. Peripheral neurolysis. In: Patt RB ed. Cancer Pain. 1st ed. Philadelphia: J.B. Lippincott, 1993:359–337.

ADDITIONAL READING

• Chauhan S, Forsmark CE. Pain management in chronic pancreatitis: A treatment algorithm. Best Pract Res Clin Gastroenterol. 2010;24(3):323–335. • World Health Organization. Cancer Pain Relief. 2nd ed. 1996. • Singh ND. Celiac plexus blocks. In: Interventional Pain Management, Gupta A (Ed.). New York, NY: Oxford University Press.

See Also (Topic, Algorithm, Electronic Media Element) Autonomic nervous system

CLINICAL PEARLS

• The celiac plexus is an aggregate of ganglia and a dense network of nerve fibers uniting, crossing through, and surrounding the ganglia that innervates most of the digestive tract. • The two principal techniques performed via the posterior approach are the deep SNB or true CPB. Although the CPB and SNB are anatomically different procedures, their clinical effect and potential complications are virtually indistinguishable. • The antecrural, or true celiac plexus block, involves needle placement anterior to the diaphragmatic crura. Theoretical advantages of this technique are that it can be done unilaterally, requires less total neurolytic injectate, and minimizes neurologic complications by limiting the spread of neurolytic agent (exclusive preaortic spread), although this has not been proven in studies. • Radiological imaging is considered the standard of care to identify the needle tip location while it is advanced, as well as assess final needle position with radiocontrast before injection of neurolytic material. • The physician must understand the potential complications in order to balance the potential risks with the benefits of the procedure, enhance optimal patient selection, reduce the incidence of complications, as well as maintain a high index of suspicion should they occur. Risks include hypotension, nerve injury, diarrhea, and pneumothorax. • Alcohol and phenol are neurolytic agents commonly used. Studies have not shown a strong benefit of one over the other in clinical practice.

CELL MEMBRANE

Dorothea Rosenberger Parravano, MD, PhD

BASICS DESCRIPTION

• A lipid cell membrane surrounds the cell and the majority of its intracellular organelles. Its primary function is to control passage of substances to establish and maintain intracellular homeostasis. • Cell membranes can be excitable (neurons and muscle cells) and nonexcitable (tubular or cutaneous cells). • Cell membranes are also involved in cell-to-cell adhesion, storage of molecules, receptor binding, cellular signaling, and intercellular communication processes. PHYSIOLOGY PRINCIPLES

• Active and passive transport are mechanisms for ion, molecule, and protein transfer through the cell membrane. – Passive transport involves movement of either particles or charge from high concentration to low concentration (diffusion). Ion flow through cell membranes is based on the electrochemical gradient for that specific ion and its physical properties. The “Nernst Equation” defines the voltage gradient at which intra- and extracellular equilibrium for a single ion is reached. – Active transport requires energy (adenosine triphosphate, ATP) to transport against a gradient where passive transport (diffusion) occurs along the concentration gradient. Primary active transport mechanisms obtain energy directly from ATP hydrolysis. Released phosphate is available for phosphorylation of carriers. Na+–K+–ATPase is an active transporter of Na+ and K+ ions against their concentration gradient to maintain a transmembrane, electrochemical potential/gradient. Secondary active transport involves a carrier that has binding sites for a specific ion and another substance to be carried along with the ion. The co-transported substance can travel in the same or the opposite direction of the ion. An example of this is Na+-glucose transporters in the intestinal mucosa. Endo- and exocytosis are active transport mechanisms involving formation of membranebound vesicles for uptake and release of extracellular and intracellular macromolecules. Transport vesicles are formed by invagination of the membrane. Examples of this include: Acetylcholine in the motor end-plate is excreted out of synaptic vesicles via exocytosis and the uptake of cholesterol occurs through receptor-mediated endocytosis. • Membrane receptors and channels – Cell membrane receptors are required for intracellular uptake of amino acids, catecholamines, peptides, and complex molecules or pharmaceuticals. – Receptors and channels can be ligand-, voltage-, or mechanically gated. – Ligand-gated ion channels are controlled by chemical messengers (e.g., acetylcholine).

– Voltage-gated receptors require electrical conformation changes and are controlled by changes in membrane potential. Voltage-gated Na+ channels and K+ channels are found in membranes of electrically excitable nerve or muscle cells. – Mechanically gated or metabotropic receptors have G protein-mediated effects. G proteins can control the release of second messengers that have stimulatory or inhibitory effects. Several G proteins may be activated by a single receptor and are capable of amplifying a signal through several effector proteins associated with one specific G protein. G protein receptors regulate neurotransmitter release in the sympathetic and parasympathetic nervous system. • Electrical membrane potentials – The resting potential of all living cells is called the membrane potential. – Generation of an action potential is the ability of a nerve or muscle cell to greatly change the ion conductance of their membrane in response to a stimulus, leading to impulse propagation along the neuron (sensory qualities such as pain) or resulting in contraction and relaxation of skeletal and smooth muscle cells.

ANATOMY

• Cell membranes consist of a double layer of phospholipids, cholesterol, and glycolipids (Figure 1).

FIGURE 1. Cell membrane, lipid bilayer with integral membrane proteins.

• The lipid bilayer determines the basic structure of the cell membrane and separates the cell interior from the extracellular space. Fluidity of the bilayer allows individual lipid molecules to diffuse rapidly within their monolayer. However, the bilayer is highly impermeable for most polar molecules. • Inner and outer membrane layers have variable amounts of lipids, reflecting different functions of the specific cell membrane. • Phospholipids and their fragments are involved in intracellular signaling pathways. They are amphipathic with a polar and a nonpolar end. Polar ends are oriented outward, nonpolar ends inward. • Cholesterol helps maintain membrane integrity, plays a role in cell signaling, and maintains membrane fluidity (separates the phospholipids so that the fatty acid chains do not come together and crystallize). It may comprise up to half of the cell membrane. • Glycolipids are only found in the outer cell membrane. • Polysaccharide chains (glycocalyx) coat the extracellular surface of membrane proteins. The glycocalyx protects the cell surface from chemical and mechanical damage and are part of the extracellular matrix. • Proteins are embedded within the bilayer; they can also interrupt the bilayer. • Integral membrane proteins interrupt the bilayer. Ion channels, adhesion molecules, carrier proteins, second messengers, and G proteins are integral membrane proteins involved in transmembrane transport of substances. DISEASE/PATHOPHYSIOLOGY

• Cerebrum: The blood–brain barrier is formed by tight junctions around cerebral capillaries to separate blood from cerebrospinal fluid. The barrier maintains concentrations of glucose, neurotransmitters, and other essential substances at different levels from the rest of the body, and prevents many pathogens from entering the brain. It is usually impermeable to large or polar molecules, and only variably permeable to ions and small hydrophilic nonelectrolytes. Barbiturates, propofol, etomidate, and benzodiazepines can cross the blood–brain barrier. Whenever the cell-to-cell junctions are disrupted, water, electrolytes, and large hydrophilic molecules can enter perivascular brain tissue and lead to vasogenic cerebral edema. • Cardiac: Electrolyte disorders can lead to disturbed electrical conduction due to changes in the resting membrane potential. Hyperkalemia increases the resting membrane potential (less negative; e.g., -90 mV to -80 mV) and increases the speed of repolarization. • Pulmonary: Oxygen and carbon dioxide move between air and blood by diffusion through the alveolar–capillary barrier down a partial pressure gradient. Disruption of the basal membrane can lead to increased protein (colloidal) movement, which creates an oncotic pressure gradient for water movement (Starling’s equation) into the pulmonary parenchyma. This disturbance leads to “thickening" of the alveolar-capillary barrier as well as increases alveolar collapse (decreased FRC); diffusion of oxygen and carbon dioxide can be markedly affected (noncardiogenic pulmonary edema). • Intestinal: Gastric parietal cells secrete H+ into the gastric lumen in exchange for K+ by the H+–K+ ATPase. Acid secretion is stimulated by histamine via H2 receptors (G protein driven mechanism) as well as acetylcholine via M3 muscarinic receptors (Ca2+ as second

messenger). Overstimulation leads to high gastric acidity and risks disruption of the intact mucosal barrier, causing tissue ulceration. Pharmacologic agents such as omeprazole block the H+-K+ pump to decrease gastric acidity. • Renal: Filtration, absorption, concentration, and excretion of urine depend on receptors, carriers, channels, and pores in tubular cells and the nephron. Increased permeability of tubular cells leads to influx of proteins into the urine, a first sign of renal insufficiency. Defects in the renal countercurrent transporter impair its concentrating ability and can manifest as polyuria or anuria. Aminoglycoside antibiotics can damage tubular epithelium and disrupt cellular fluidity and Na+-K+ ATPases, potentially causing renal failure. • Endocrine: – Iodine uptake into the thyroidal cell depends on a secondary active Na+/I cotransporter. Nitrates or perchlorates compete with iodine for intracellular uptake on the transporter resulting in decreased iodine uptake. This leads to a decline in circulating thyroid hormones, increased TSH, and goiter formation. – Glucose enters the cell via facilitated diffusion or by secondary active transport with Na+. Glucose transporters are potential targets for novel antidiabetic drugs. • Anaphylaxis: A trigger substance induces mainly IgE-related pathways. IgE is produced in response to allergen exposure, and binds to a high-affinity IgE membrane receptor on mast cells and basophils. Activation leads to release of various inflammatory mediators (e.g., histamine, tryptase, prostaglandin, and leukotrienes) affecting integumentary, respiratory, GI, cardiovascular, and central nervous systems. Hypotension, tachycardia, and edema are clinical symptoms of disrupted cell membrane integrity and binding of mediators to cellular membrane receptors.

PERIOPERATIVE RELEVANCE

• Benzodiazepines bind to GABA receptors and enhance GABA neurotransmitter binding with resultant chloride ion transport into the cell (hyperpolarizes the membrane resting potential). • Local anesthetics inhibit fast Na+ channels that are responsible for Phase 0 depolarization. Perioperatively, they are used to disrupt sensory, motor, and autonomic nerve conduction. Effects have variable duration, depending on the receptor affinity and the degradation, distribution, and metabolism of the substance and its byproducts. • Opioids bind to μ, kappa, ORL1, and NMDA receptors in the cerebrum, spinal cord, and several peripheral tissues, leading to pain relief, respiratory depression, sedation, itching, and constipation. • Propofol, etomidate, and ketamine bind to GABA and NMDA receptors, inducing reversible loss of consciousness and sensation. Different affinities to GABA receptors, their subtypes, and specific subunits determine the action, duration, and side effects of these induction agents. – Propofol binds to GABA-A receptors. Propofol also blocks Na+ channels and might have an effect on various endogenous opioid receptors. – Etomidate binds also to GABA-A receptors. – Ketamine is an antagonist at the NMDA receptor and also binds to dopamine and opioid receptors depending on the given dose.

• Neuromuscular blocking drugs can be used to facilitate intubation, surgical procedures, and mechanical ventilation. – Nondepolarizing agents (e.g., pancuronium) are nicotinic receptor competitive antagonists; they prevent acetylcholine binding. – Depolarizing agents (e.g., succinylcholine) mimic acetylcholine at the cell receptor. They bind to the receptor and depolarize the muscle cell (causing contraction), and then prevent acetylcholine from binding to the receptor until they detach. • Inhalational agents have sedative and hypnotic effects that are thought to be caused by binding to NMDA receptors (acting as receptor blocking) and GABA receptors (inhibiting effects enhanced). However, most of the cellular mechanisms are still unknown.

EQUATIONS

• Nernst Equation: Determines ion flux across the membrane. Flux is dependent on the gradient between intra- and extracellular ion concentration.

REFERENCES

1. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell, 5th ed. New York: Garland Science, 2008. 2. anong, WF. Review of Medical Physiology, 22nd ed. New York: McGraw Hill Medical/Lange, 2008. See Also (Topic, Algorithm, Electronic Media Element) • Diffusion • Blood–brain barrier • PaO2 • PaCO2

• Hyperkalemia

CLINICAL PEARLS

Malignant hyperthermia (MH): The combination of volatile anesthetics and/or succinylcholine in individuals with inherited defects at the ryanodine receptor can lead to a life-threatening hypercatabolic state. About 6 gene loci have been identified to be responsible for this reaction, along with at least 25 possible mutations in the gene expressing ryanodine receptor protein in the sarcoplasmatic reticulum (SR). Specific gene loci are responsible for forming Ca2+ channels that control Ca2+ flux intra- and extracellularly from the SR. Drastic

increases in Ca2+ lead to muscle rigidity, a leading symptom of MH. Other symptoms include a high end-tidal carbon dioxide, temperature increase, tachycardia, hyperkalemia, respiratory, and metabolic acidosis and rhabdomyolysis. Dantrolene, a muscle relaxant itself, can block further Ca2+ excretion from the SR and is the only know effective antidote for an MH crisis.

CELL SALVAGE

Alan Ashworth, MBChB, FRCA, FFICM Andrew A. Klein, MD

BASICS DESCRIPTION

• Autologous transfusion describes returning the patient’s own blood to them, whereas allogeneic transfusion describes transfusing someone else’s blood to a patient. Autologous transfusion potentially avoids many of the adverse effects associated with allogeneic transfusion. • Cell salvage, commonly referred to as “cell saver,” involves suctioning, washing, and filtering blood from the surgical field, then returning it to the patient. This is the most common autologous transfusion technique. • It is commonly (but not exclusively) used in cardiac, neurologic, hepatic, vascular, and orthopaedic surgery where expected blood loss is significant enough to merit the cost. • History of cell salvage. First used in the 18th century when managing patients with postpartum hemorrhage. Blood-soaked swabs were washed in saline and then the mixture was reinfused; not surprisingly, this was associated with a high mortality. Throughout the 19th century, experimentation with cell salvage and autologous transfusion continued. In 1931, blood salvaged from hemothoraces was directly reinfused into patients. The first cell salvage autotransfusion device was developed in 1943 by straining suctioned blood through a cheese cloth, which forms the basis of modern cell salvage machines. PHYSIOLOGY PRINCIPLES

• The process of cell salvage can be separated into collection, washing, and reinfusion. • Collection. A dedicated double-lumen suction device allows collection of red blood cells (RBCs) from the operative field. One lumen suctions blood from the operative field and the other lumen adds a predetermined volume of anticoagulant flush to the salvaged blood. Heparinized saline flush is commonly used; its composition depends on manufacturer guidelines, and typically consists of 30,000 U of heparin in 1,000 mL of 0.9% saline. Some centers substitute this with a citrate solution. The anticoagulated blood passes through a filter to remove debris and is then collected in a reservoir. • Washing. Centrifugation separates the components of blood into RBCs and plasma. The washed RBCs are then filtered across a semipermeable membrane, which removes free hemoglobin, plasma, platelets, white blood cells, and heparin. • Reinfusion. Salvaged RBCs are then suspended in normal saline at which point they can be reinfused via any peripheral or central venous catheter. The salvaged RBCs may be transfused immediately or within 6 hours (1). The solution has a hematocrit of 50–70%, depending on the cell saver machine. In practice, however, some heparin (up to 5%) is not removed, and a variable quantity of other substances such as leukotrienes and complement may also be mixed with the red cells. Plasma containing clotting factors and platelets are

removed and wasted during the washing process.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The use of cell salvage in obstetrics and cases of malignancy or microbiological contamination remains controversial. • Obstetrics. There exists a theoretical risk of precipitating amniotic fluid embolus (AFE) if amniotic fluid is not completely removed by the washing process. Recent evidence has shown that reinfusion of RBCs salvaged during elective Caesarean section is not associated with an increase in the incidence of AFE (2). • Malignancy. Previously, was an absolute contraindication due to the theoretical risk of disseminating tumor cells. However, studies in patients with urological malignancy have showed that cell salvage and autologous transfusion were not associated with an increase in biochemical recurrence rates of prostate cancer and was effective at reducing allogeneic blood transfusion requirements (3). Therefore, certain cases may merit the use of cell salvage during surgery for malignancy, provided the risks and benefits are discussed with the surgeon and patient. • Infection. In cases where there is potential contamination of salvaged blood with bowel contents or purulent material, the use of cell salvage is contraindicated by the manufacturers. However, there is some evidence that cell salvage in combination with a leucocyte depletion filter (LDF) may be safe. Therefore, infection or enteric content should no longer be considered an absolute contraindication. In cases where there is gross enteric content contamination, the surgeons should avoid suctioning the most contaminated areas, broad spectrum antibiotics should be administered, and the volume of saline wash should be increased. Risks and benefits of cell salvage use should be discussed with the surgeon and patient preoperatively.

PERIOPERATIVE RELEVANCE

• The aim of cell salvage is to reduce or eliminate the need for allogeneic blood transfusion. A recent meta-analysis found that cell salvage was efficacious in reducing the need for allogeneic blood transfusion in adult elective surgery by 39%, with an average saving of 0.7 units per patient (4). This could – Reduce the risks of infectious and noninfectious complications of allogeneic blood transfusions. – Increase the mean erythrocyte viability compared to autologous blood. Salvaged RBCs maintain their normal biconcave disk shape, whereas allogeneic blood assumes an echinocyte shape (after 14 days), which is thought to impair its ability to flow through the capillary beds. – Increase 2,3-diphosphoglycerate (2,3-DPG) compared to autologous blood, which improves oxygen-carrying capacity and tissue oxygen delivery. – Increase patient survival. Studies have shown that following an esophagectomy, there is increased survival, which may be due to the lack of immunomodulatory effects of salvaged blood compared to allogeneic blood. – Have immunostimulatory effects that may reduce postoperative infections. • Cell salvage should be considered in advance for cases where blood loss may exceed 1000 mL in adults and 10 mL/kg in pediatrics.

• If unsure about blood loss, consider setting up cell salvage as backup. This means prepare the reservoir, suction tubing, and heparinized saline flush (inexpensive and quick). If blood loss (after subtracting heparinized saline and any other wash fluids) occurs, the machine can then be set up to process the blood. If blood loss is minimal, this can then be discarded. Such a policy would generate considerable savings in terms of allogeneic blood, and potentially in healthcare costs. • Cell salvage complications. The literature shows that complications associated with the use of cell salvage are rare. In cases where patients are autotransfused large volumes of processed RBCs, this may be accompanied by coagulopathy because of the loss of clotting factors and platelets (see above). – In cases where the volume of blood washed is less than 30% of the patient’s total blood volume, studies have shown that there is no increase in perioperative bleeding, and that no coagulopathy can be detected (5). – The point at which coagulopathy associated with cell salvage becomes clinically relevant varies between patients, but it is not likely until >50% of the patient’s blood volume has been washed (around 3,000 mL in the average sized adult). – If the patient is actively bleeding, thromboelastography, prothrombin time, fibrinogen, and platelet counts should be performed. – Blood product replacement with plasma, cryoprecipitate, and/or platelets should be performed. • Allogeneic blood transfusions have been affiliated with the following risks: – Tumor recurrence – Postoperative infections – Acute lung injury – Perioperative myocardial infarction – Postoperative low-output cardiac failure – Increased morbidity and 5-year mortality – Immunomodulation is dose dependent; transfusion of allogeneic blood is associated with decreased transplant rejection. • Developing abnormal antibodies. Exposure to multiple units of allogeneic blood makes future cross-matching more difficult and time consuming.

REFERENCES

1. shworth A, Klein AA. Cell salvage as part of a blood conservation strategy in anaesthesia. Br J Anaesth. 2010;105:401–416. 2. Geoghegan J, Daniels JP, Moore PAS, et al. Cell salvage at caesarean section: The need for an evidence-based approach. Br J Obstet Gynaecol. 2009;116:743–747. 3. Nieder AM, Carmack AJK, Sved PD, et al. Intraoperative cell salvage during radical prostatectomy is not associated with greater biochemical recurrence rate. Urology. 2004;65:730–734. 4. Carless PA, Henry DA, Moxey AJ, et al. Cell salvage for minimizing perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2006;4:CD001888. 5. Klein AA, Nashef SAM, Sharples L, et al. A randomized controlled trial of cell salvage in

cardiac surgery. Anesth Analg. 2008;107:1487–1495.

See Also (Topic, Algorithm, Electronic Media Element) • Autologous blood transfusion • Transfusion infections • Blood substitutes

CLINICAL PEARLS

• Cell salvage (“Cell Saver”) is the most common form of autologous blood transfusion. RBCs are isolated and purified from suctioned blood, resuspended in saline, and reinfused in the patient. • In elective cases, cell salvage has been shown to increase erythrocyte viability, oxygencarrying capacity, possibly reduce infection, and increase survivability compared to allogeneic transfusion. • Cell salvage has generally been contraindicated in cases where reinfusion could theoretically spread pathology (obstetrics, malignancy, cases involving infection). However, studies have not supported this finding and certain cases may merit its use after careful discussion with the surgeon and patient.

CEMENT IMPLANTATION SYNDROME Valbona Kanarek, MD Stephen P. Winikoff, MD

BASICS DESCRIPTION

• Cement implantation syndrome (CIS) is a rare and potentially fatal complication in patients undergoing cemented total hip arthroplasty (THA). • Methylmethacrylate (MMA), or bone cement, is utilized to secure the implant to the joint. It can result in peripheral vasodilatory effects, fat and marrow embolism, and activation of the clotting cascade in the lungs. • CIS occurs around the time of prosthetic insertion and is characterized by a constellation of clinical features: – Hypoxia – Decreased systemic vascular resistance (SVR) – Increased pulmonary vascular resistance (PVR) – Confusion – Cardiac arrhythmias, or arrest EPIDEMIOLOGY Prevalence

• True incidence is unknown, likely from underreporting and/or a wide variety of clinical presentations. • Hypotension during THA: 2% as defined as a reduction in SBP>30% (1)[C] • Desaturation of more than 5%: 17% (2)[C] • CIS has been associated with other procedures (vertebroplasty, total knee arthroplasty, hip hemiarthroplasty) where bone cement is used.

Mortality

• Intraoperative mortality due to cardiopulmonary complications in patients undergoing cemented THA: 0.11% (0% for those with uncemented THA) (2)[C]. • Cemented THA for pathological bone fractures: 4.3% (1)[C]. • Increased in elderly patients and those with impaired cardiopulmonary function (2)[B].

ETIOLOGY/RISK FACTORS

• Injection of pressurized bone cement intramedullarily • Increased age • Poor preexisting physical reserve • Pulmonary hypertension • Impaired cardiopulmonary function • Bone metastases with pathologic hip fractures, femoral fractures

• Patent foramen ovale (PFO): increased risk for paradoxical emboli and neurological sequela • A previously uninstrumented femur increases the risk for CIS since there may be more potential embolic material, and a previously cemented inner surface of the femur becomes a less permeable surface.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Bone cement is utilized to improve femoral contact surface area with the prosthesis. • The exact pathogenesis of CIS is not well understood. Several models have been suggested to account for the hemodynamic and pulmonary changes and involve either mechanical and/or chemical causes. • The MMA monomer model suggests a chemical-mediated pathogenesis with circulating MMA particles causing worsening pulmonary artery pressure (PAP) or reducing SVR (3)[A] (1)[B]. These monomers have been linked to histamine and IgE release (possible complement activation) with resultant: – Pulmonary artery vasoconstriction – Increased microvascular permeability and noncardiogenic pulmonary edema – Bronchospasm – V/Q mismatch (due to decreased ventilation and shunting of nonoxygenated blood to the systemic circulation) – Hypoxia • The embolization model suggests a mechanical and chemical model. Bone marrow, fat, fibrin, and platelet debris emboli are seen with transesophageal echo (TEE) in the right atrium during preparation of the femoral canal, prosthesis insertion, and cement placement (4)[A]. This can result in – Direct mechanical obstruction of the pulmonary vasculature causing V/Q mismatch (dead space: Ventilating but not perfusing) and increased afterload to the right ventricle (RV) with subsequent RV dysfunction (increased central venous pressure, CVP, increased JVD) – Chemical endothelial damage of the pulmonary vasculature from vasoactive substances such as thrombin, platelet activating factor, and endothelin-1 Increased shunt Increased PVR Increased RV afterload Decreased cardiac output (CO) and decreased SV (4)[B] with resultant cerebral and cardiac ischemia (tachyarrhythmias, ST changes). Tissue thromboplastin and adenine nucleotides cause profound reductions in SVR with worsening cerebral hypoperfusion leading to confusion, or loss of consciousness. • Multimodal model. CIS is most likely a constellation of the above processes (1,5)[B]. However, the extent to which each of the above models contributes to the clinical presentation of the patient will depend on the patients preexisting cardiovascular function. The impact of mechanical insult (fat, marrow, platelet debris) and chemical insult (vasoactive substances from pulmonary endothelial damage) on SVR, PVR, cardiac function, and V/Q mismatch (increase shunt and increase dead space) varies in severity among patients. • Paradoxical embolization of marrow debris occurs in the presence of a PFO. The debris bypasses the lungs and spills into the systemic, cerebral, or coronary arteries which can lead

to embolic strokes and acute coronary ischemia. Embolization is not always associated with these hemodynamic changes and the degree of embolization does not correlate with the severity of hypotension or hypoxemia (6[A].

PREVENTATIVE MEASURES

• Anesthetic strategies to minimize the occurrence of CIS: – Maintain euvolemia – Increase FIO2 prior to cementing.

– Avoid nitrous oxide in high risk patients; it can increase the size of air emboli as well as increase PVR. • Surgical strategies to decrease the occurrence of CIS: – Drill a vent hole in the femur prior to prosthesis insertion; this decreases the risk of intramedullary hypertension and emboli formation (5)[B]. – Utilize a cementless prosthesis. This has the added benefit of lasting longer, but requires that the patient has good bone growth (younger population) and can increase recovery time.

PREOPERATIVE ASSESSMENT • ETCO2 decreases are sensitive indicators of worsening dead space. CIS can result in

microemboli that can lodge in the pulmonary vasculature as well as decreased cardiac output. Carbon dioxide continues to be produced by tissues, but in both circumstances, cannot reach alveolar capillaries for exhalation from alveoli (PaCO2 increases).

• In addition to standard anesthetic monitoring, invasive hemodynamic monitoring is recommended for high-risk patients. • CVP monitoring to guide: – Fluid management – Right atrial filling pressures – Inotrope administration – However, this is not a reliable monitor for left ventricular function • Arterial pressure monitoring can provide – Beat-to-beat blood pressure monitoring – PaO2 measurements can detect changes in oxygen partial pressure despite the pulse oximetry reading 100% • Pulmonary artery catheter (PAC) can provide – CVPs – PAPs – Left ventricular end-diastolic pressures – CO – Mixed venous oxygen saturation – SVR • TEE for high-risk patients to monitor for – Large emboli

– Segmental wall motion abnormalities – Cardiac function

DIFFERENTIAL DIAGNOSIS • Acute coronary syndrome • Pulmonary embolus • Cardiogenic shock • Cerebrovascular accident

TREATMENT • 100% inspired oxygen to optimize oxygen delivery to ischemic areas. • RV hemodynamic support with ephedrine, epinephrine, or milrinone. Milrinone is a phosphodiesterase inhibitor that increases contractility while decreasing afterload (in this case PVR). • SVR support with norepinephrine, ephedrine, or epinephrine. • Cardiopulmonary resuscitation with compressions in the event of PEA.

FOLLOW-UP If hemodynamic stability is achieved, consider continuing the surgical procedure.

REFERENCES

1. Donaldson AJ, Thomson HE, Harper NJ, et al. Bone cement implantation syndrome. B J Anaesth. 2009;102:12–22. 2. Parvizi J, Holliday AD, Ereth MH, et al. Sudden death during primary hip arthroplasty. Clin Orthop Relat Res. 1999;369:39–48. 3. Ereth MH, Weber JG, et al. Cemented vs. non-cemented THA, embolism, hemodynamics and intrapulmonary shunting. Mayo Clinic Proc. 1992; 67:1066–1074. 4. Urban M, Sheppard R, Gordon M, et al. Right ventricular function during revision total hip arthroplasty. Anesthesia Analgesia. 1996;82:1225–1229. 5. Christie J, Robinson C, Singer B, et al. Medullary lavage reduces embolic phenomena and cardiopulmonary changes during cemented hemiarthroplasty. J Bone Joint Surg. 1995;77B:456–459. See Also (Topic, Algorithm, Electronic Media Element) • Fat embolism syndrome • Dead space • Pulmonary artery catheter • Transesophageal echocardiogram • Atrial septal defect

CLINICAL PEARLS

• Vigilance to physiologic parameters during cementing. • Intravenous fluid repletion, invasive monitoring in patients with poor reserve.

CENTRAL LINES Edna Ma, MD

BASICS DESCRIPTION General

• Central venous catheter (CVC) placement involves cannulization of a large vein of the neck (internal jugular or external jugular vein), the chest (subclavian vein), or groin (femoral vein). • CVC is used for the administration of – Medications: Vasoactive drugs, hyperosmolar medications, chemotherapeutic agents, longterm antibiotic use – Cardiovascular (CV) measurements: Central venous pressure – Venous access for frequent blood tests: Including mixed venous oxygenation saturation – Cardiac pacing – Hemodialysis – Nutrition: Total parenteral nutrition (TPN) • Surgical placement of central lines are often performed in the operating room, entail larger bores, provide longer-term access, and have the option of utilizing an open approach. • Tunneled catheters are inserted in the operating room into either the internal jugular or subclavian veins via an open approach or “cut-down.” The distal end of the catheter is passed under the skin and emerges at a site separate from the insertion site; it is connected to either a subcutaneous port or a port that emerges through the skin for direct access. IV contrast dye may be injected to confirm vascular placement. – The advantages to having a tunneled catheter include patient comfort, stability, and prevention of infection. An implantable port lies completely under the skin so patients can swim and bathe normally. – An implantable port is a reservoir that can be filled and releases medication into the patient’s bloodstream; it is accessed with a special noncoring (Huber) needle that will not damage the ports rubber septum. – An example of a tunneled catheter with an implanted port is the “Port-a-cath,” and is used for chemotherapy or TPN. • Nontunneled catheters. Typically performed percutaneously with the catheter and its ports fixed in place at the site of insertion. – Frequently performed at the patient’s bedside – Examples include triple- or double-lumen catheters placed in the internal jugular or subclavian veins; as well as Quinton catheters, which are used for temporary access for dialysis. • PICC lines: peripherally inserted central catheters. Typically inserted through one of the veins (e.g., cephalic, basilic, and brachial vein) in the upper extremity. The catheter is

inserted through a peripheral vein and threaded so its tip rests in the distal superior vena cava or cavoatrial junction. – Typically inserted outside of the operating room, with the assistance of an ultrasound device, by doctors, physician assistants, or certified nurses.

Position

• Trendelenburg; improves vein “engorgement” and prevents air entrainment into the intravascular space. • Lateral rotation of the patient’s head can improve access to the subclavian and internal jugular veins.

Incision

• A hollow bored needle, with continuous negative pressure, is introduced through the skin until blood is aspirated. • The entry site may be enlarged using a dilator or small skin incision for catheter placement. • The catheter can be tunneled under the skin and connects to a subcutaneous port.

Approximate Time 10–30 minutes EBL Expected <10 mL

Hospital Stay

• Depends on the CVC indication • Outpatient procedure for long-term antibiotic therapy or chemotherapy.

Special Equipment for Surgery

• Ultrasound guidance device • Fluoroscopy and IV contrast dye • Postprocedure chest x-ray

EPIDEMIOLOGY Prevalence

>5 million are inserted every year in the US (1)

Morbidity

Greater than 15% have complications (2), including • Pneumothorax • Vascular injury • Infection • Thrombus • Venous air embolus • Cardiac tamponade • Hemorrhage

• Hematoma • Arrhythmias • Loss of guidewire • Valvular or cardiac perforation

Mortality

Associated with • Cardiac tamponade • Catheter or wire embolism • Vascular injury; hemothorax, hydrothorax, carotid artery injury, subclavian artery injury, pulmonary artery rupture (3)

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The anaesthetist has the option of minimal to no sedation or a general anesthetic with a laryngeal mask airway (LMA) or endotracheal tube (ETT). The decision is based on the patient’s comorbidities and ability to lie still in the Trendelenburg position as well as the surgical provider’s preference. • The two requisites of a venous air embolism (VAE) are direct communication between an air source and vasculature in addition to a pressure gradient that favors passage of air into the circulation. CVC equipment allows direct access to the vein, and when the patient is spontaneously ventilating, or obstructing, a negative pressure breath can provide the driving force.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Chemotherapy access patients could include treatment for breast or colon cancer or lymphomas. • Hemodialysis access patients could include uremia symptoms, anemia, acidosis, and volume overload. • PICC line access patient could include those in need for long-term antibiotic or chemotherapy.

History

Requires an assessment of the indication and underlying disease. Signs/Physical Exam Variable

MEDICATIONS

Peripheral nutrition infusion may be held during the procedure. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Coagulation studies • Potassium value may be performed; however, the access is often placed in order to dialyze and regain electrolyte homeostasis.

CONCOMITANT ORGAN DYSFUNCTION Variable

TREATMENT PREOPERATIVE PREPARATION Premedications

Anxiolysis as appropriate

Special Concerns for Informed Consent

When performing under sedation, a discussion with the patient and family should include realistic goals and the possibility of recollection of certain events. Additionally, the patient should be aware that they may be asked to “breath hold” during cannulation. Antibiotics/Common Organisms

Skin organisms; a third-generation cephalosporin such as cefazolin may be indicated. INTRAOPERATIVE CARE Choice of Anesthesia

• Local with only lidocaine for subcutaneous anesthesia • Sedation • General anesthesia is often chosen for pediatric, uncooperative, demented, or anxious patients; as well as patients who cannot tolerate head-down position due to comorbidities (risk for aspiration, reduced functional residual capacity, and pulmonary edema). – LMA may be considered when aspiration is unlikely. – ETT placement should be considered if there is a potential for aspiration or a difficult airway (prior neck radiation or obesity). Monitors

Standard ASA monitors

Induction/Airway Management

• Sedation: Anesthetic goals should include patient comfort for positioning (e.g., Trendelenburg, tunneling of catheter, and arms tucked) and subcutaneous infiltration of local anesthetic. • General anesthesia: ETT insertion may be improved with the assistance of muscle relaxation. If needed, consider succinylcholine for its short duration; however, it may be precluded given comorbidities (patients presenting for dialysis who have hyperkalemia). If a nondepolarizing agent is utilized, its duration of action/ability to be reversed may exceed the duration of the procedure.

Maintenance

• Sedation should be titrated cautiously. Oversedation can result in obstruction and may increase the potential for VAE during instrumentation and tunneling. • General can be maintained with volatile or IV agents.

Extubation/Emergence

• Sedation: Reorient patient that the procedure is complete. • General: Standard extubation criteria apply.

FOLLOW-UP BED ACUITY

Postprocedure upright chest x-ray to confirm placement and rule out complications. ANALGESIA

Minimal to none. Soreness at the site may be treated with acetaminophen. COMPLICATIONS

• VAE – The awake patient may present with acute dyspnea, continuous cough, gasp reflex, lightheadedness, and vertigo. Cardiac manifestations (in awake and asleep patients) include dysrhythmias, peaked P waves, ST segment changes, JVD, right heart failure, low BP, and CV collapse. – Preventive measures include Trendelenburg position and occlusion of the needle and hub during placement and removal, avoidance of deep inspiration when the patient is SV (avoids negative pressure/suction effect), and PEEP when positive pressure ventilation (PPV) is being administered. – When Trendelenburg is contraindicated (increased ICP), consider temporary positioning during insertion of the guidewire or catheter, or raising the legs to increase venous return and pressure in the right atrium. • Pneumothorax may be diagnosed by physical exam (absent breath sounds on ipsilateral side of chest +/– hypotension) and/or chest x-ray. Incidence may be minimized by the use of ultrasound guidance. Treatment typically involves chest tube placement to evacuate the pleura air and re-expand the lung. • Hemothorax; diagnosis and treatment are similar to pneumothorax.

REFERENCES

1. aad I. Intravascular-catheter–related infections. Lancet. 1998;351:893–898. 2. Sznajder JI, Zveibil FR, Bitterman H, et al. Central vein catheterization: Failure and complication rates by three percutaneous approaches. Arch Intern Med. 1986;146:259– 261. 3. Bowdle TA. Central line complications from the ASA closed claims project: an update. ASA Newsletter. 2002;66(6):11–12 & 25.

See Also (Topic, Algorithm, Electronic Media Element) • Venous air embolism • Pneumothorax • End-stage renal disease • Chest radiography • Radiation safety

CLINICAL PEARLS

• The anesthesia provider may be called on to provide care to patients requiring tunneled central line access in the operating room in the form of no sedation, sedation, or general anesthesia. • Additionally, the anesthesia provider frequently place central lines via the percutaneous approach for intraoperative or postoperative care. • VAE, pneumothorax, and hemothorax are serious and potentially fatal complications of CVC placement; efforts should be made to reduce the incidence, and treatment should be aggressive.

CEREBRAL ARTERIOVENOUS MALFORMATION Joseph R. Whiteley, DO Thomas I. Epperson III, MD

BASICS DESCRIPTION

• Brain arteriovenous malformations (BAVM) are abnormal tangles of dilated arteries and veins, known as an arteriovenous nidus, that directly shunt blood between the arterial and venous circulations without a true capillary bed. • The harmful effects of BAVMs can be the result of a mass effect, rupture (intracranial hemorrhage), ischemia to surrounding brain tissue, and the ability to incite seizure activity. • Following a BAVM rupture, surgery may be delayed until the patient has recovered from the effects of the bleed, unless the hematoma is causing clinical deterioration. • Procedures to treat brain AVMs include preparatory and therapeutic embolization, surgical resection, and stereotactic radiosurgery. EPIDEMIOLOGY Prevalence

Approximately 1 per 100,000 adults per year are newly diagnosed. Children comprise 3–19% of all AVM patients. Prevalence

Estimated at ∼0.01% of the general population, with reported rates from 0.001% to 0.52% Morbidity

• Accounts for 1–2% of all strokes; in young adults, it is responsible for 4% of all strokes and 9% of subarachnoid hemorrhages. • Of AVM hemorrhages, 30–50% result in permanent neurologic deficits.

Mortality

Hemorrhage risk 2–4% per year, with 5–10% of hemorrhages resulting in death. ETIOLOGY/RISK FACTORS

• Cause remains unknown. Two hypotheses for AVM pathogenesis are embryonic agenesis of the capillary system and retention of primordial vascular connections between arteries and veins. However, intrauterine and neonatal ultrasonography do not support this assertion. • Current thought is a multifactorial etiology, with contributions from – Genetic polymorphisms: Active angiogenic and inflammatory phenotypes, such as overexpression of vascular endothelial growth factor-A and matrix metalloproteinase. – Environmental exposures, while lacking strong evidence, may include unremarkable episodes of trauma, infection, and inflammation.

• Vast majority are sporadic, not familial.

PHYSIOLOGY/PATHOPHYSIOLOGY

• AVMS are high-flow, low resistance shunts that lack a true capillary bed. Pathologic consequences can result from: – Diversion of blood from surrounding tissue can result in inadequate perfusion and ischemia. – Rupture of a feeding artery in a small AVM, or more commonly, from the eventual rupture of dilated veins exposed to high arterial pressures. Normally, veins receive low pressure blood from capillary beds; whereas with AVMs, the thin, nonmuscular walls of veins face abnormally high transmural pressures. • AVMs are dynamically changing vascular pathologies; they can enlarge or shrink over time. Growth, remodeling, and/or regression of brain AVMs are thought to be due to a combination of factors: both molecular (growth factors and extracellular proteins) and physiologic (arterial and venous blood flow forces).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• For both open craniotomy resection and interventional embolization procedures, the goals of anesthesia are to provide a motionless field, maintain cerebral perfusion pressure (CPP), provide brain relaxation and optimize the surgical field through controlled ventilation and/or diuretics, and to decrease brain tissue oxygen demand by lowering cerebral metabolic rate with anesthetic agents. • Rapid and controlled emergence with tight hemodynamic control and early postoperative neurologic exam. • In the setting of rupture: hypotension is induced; cerebral protection is maximized with varying combinations of barbiturates, propofol, or volatile agents to decrease cerebral metabolic rate; and hyperglycemia and hyperthermia are avoided.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Headaches (specifically migraines) • Vertigo/dizziness • Dysarthria or apraxia • Numbness and tingling • Bruit – audible to patient

History

Most commonly discovered in young adults aged 20–40 who present with hemorrhage or seizure. Signs/Physical Exam

• Seizures • Neurologic deficits • Intracranial hemorrhage, most common presenting sign (20–50% of patients).

TREATMENT HISTORY

• Surgical resection (craniotomy, microsurgical) for low-grade lesions (Spetzler–Martin grading scale I–III); high-grade lesions require multimodal treatment. Most commonly used in pediatric cases. • Embolization (minimally invasive) may be therapeutic; or can be used to obliterate fistulas and feeding arteries to decrease blood flow in preparation for surgery. • Stereotactic radiosurgery (noninvasive) for lesions <2 cm and in deep locations not easily approachable by microsurgical or endovascular techniques. • Observant management may be indicated in older patients with comorbid conditions.

MEDICATIONS

• Antiepileptics: Phenytoin, levetiracetam, carbamazepine • Antihypertensives – Direct-acting vasodilators: Sodium nitroprusside, hydralazine – Adrenoreceptor antagonists: Labetalol, esmolol – Calcium channel blockers: Nimodipine, nicardipine, clevidipine • Osmotic agents (mannitol, hypertonic saline) following an intracranial bleed may be administered to create an osmolar gradient across an intact blood–brain barrier. This results in brain relaxation and decreases intracranial pressure (ICP). DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CT: Sensitive for detecting acute hemorrhage • Computed tomographic angiography (CTA): Allows visualization of AVM vascular detail. • MRI or magnetic resonance angiography (MRA): Allows visualization of the AVM and surrounding structures. • Digital subtraction angiography (DSA): The gold standard to evaluate AVM. Detects associated aneurysms, venous outflow obstruction, and patterns of venous drainage. • Superselective WADA testing (intracarotid sodium amobarbital procedure). One hemisphere of the brain is briefly anesthetized and the patient undergoes a series of language and memory-related tests. Determines hemisphere dominance and whether surgery will affect language and memory. • Functional MRI helps assess the relationship between brain function and cerebral hemodynamics. The imaging reflects task-related local changes in the vascular response of brain tissue. It serves as an indirect measure of neural activity and is used to plan surgery of motor and language areas. CONCOMITANT ORGAN DYSFUNCTION

Cerebral aneurysms found in 3–20% of patients with AVMs CIRCUMSTANCES TO DELAY/ CONDITIONS

Delay AVM surgery in the setting of acute intracranial hemorrhage unless the hematoma is causing deterioration in neurologic function through increased ICP. CLASSIFICATIONS

Spetzler–Martin grading scale for AVMs: The higher the grade, the greater the surgical risk. Grade I–III are typically offered surgical resection; Grade III and higher are typically offered surgery after embolization and/or radiotherapy. See Table

TREATMENT PREOPERATIVE PREPARATION Premedications

Premedication with benzodiazepines if no existing neurologic deficits. Avoid when there is a depressed level of consciousness (LOC). Special Concerns for Informed Consent

In patients who are present with hemorrhage or cerebral ischemia, the resultant aphasia, dysphasia, or depressed LOC can make communication difficult. INTRAOPERATIVE CARE Choice of Anesthesia

General endotracheal anesthesia Monitors

• Standard ASA monitors • Arterial line (embolization and surgical) for continuous, direct BP monitoring and blood sampling; consider placing preinduction. • Central venous access may be considered for surgical resection of large AVMs that have the potential for large blood loss. • Neurophysiologic monitoring is often used during AVM surgery. EEG monitoring can be used intraoperatively to detect ischemia and also to guide barbiturate titration during “burst suppression.” • Somatosensory-evoked potentials (SSEPs) can be used to monitor perfusion of the sensory cortex and brainstem. Induction/Airway Management

• A smooth controlled induction should be performed to maintain adequate CPP. Hypotension should be avoided due to a risk of ischemia to hypoperfused regions that are adjacent to the arteriovenous nidus. • Attenuate hypertensive responses to laryngoscopy, intubation, and placement of pins for head fixation. Techniques include brief laryngoscopy, deepening anesthetic, and/or administering short-acting antihypertensives such as sodium nitroprusside or esmolol. Maintenance

• Volatile, intravenous, or mixed technique may be used. Total intravenous anesthesia can optimize SSEPs and motor-evoked potentials (MEPs).

• For craniotomies, adequate brain relaxation and ICP control can decrease ischemia from retractors and facilitate surgical access. Techniques include the “head up” position (15%), diuretics/osmotherapy, cerebrospinal fluid drainage, mild hypocapnia, and avoidance of cerebral dilating anesthetics. • Barbiturates can be used to achieve “burst suppression” of the EEG. Barbiturate loading results in delayed emergence. Animal data suggests propofol is an effective alternative agent if thiopental not available. • Fluids are usually isotonic, nonglucose containing solutions. • Severe bleeding during AVM resection most commonly occurs due to inadequate occlusion of feeding arteries; hypertension-induced rupture is very rare. Induced hypotension may be useful when this occurs (especially with large AVMs that have a deep arterial blood supply).

Extubation/Emergence

• Smooth controlled emergence. • Avoid hypertension and coughing or bucking. Treat with rapidly acting agents such as lidocaine, sodium nitroprusside, nitroglycerin, esmolol, and nicardipine/clevidipine. • Early neurologic examination to detect surgical complications and hematoma formation.

FOLLOW-UP BED ACUITY

Intensive care unit (ICU) COMPLICATIONS

• Rupture, 1–2% • Hyperemic complications: Increased blood flow • “Normal-perfusion pressure breakthrough” describes brain swelling and hemorrhage following AVM resection or embolization. It is believed that normal blood flow autoregulation is impaired due to longstanding hypoperfusion. AVM resection results in shunting of blood to hypoperfused regions; resumption of normal arterial pressures causes hyperperfusion, edema, and bleeding. • Occlusive hyperemia results from venous outflow obstruction caused by surgical ligation of veins in adjacent normal tissue.

REFERENCES

1. riedlander RM. Clinical practice. Arteriovenous malformations of the brain. N Engl J Med. 2007;356(26):2704–2712. 2. Inoue HK, Negishi M, Hirato M, et al. Treatment of unruptured arteriovenous malformations in the brain. J Clin Neurosc. 1998;5Suppl:61–64. 3. Hudspith MJ, Popham PA. The anaesthetic management of intracranial haemorrhage from arteriovenous malformations during pregnancy: Three cases. Int J Obstet Anesth. 1996;5(3):189–193. 4. Hashimoto N, Nozaki K, Takagi Y, et al. Surgery of cerebral arteriovenous malformations.

Neurosurgery. 2007;61(1):SHC-375–SHC-389. 5. endo AA. Intracranial vascular surgery. Anesthesiology Clin N Am. 2002;20(2):377–388. See Also (Topic, Algorithm, Electronic Media Element) • Burst suppression • Craniotomy for intracranial hemorrhage • Somatosensory- and motor evoked potentials • Intracranial hypertension

CODES ICD9

747.81 Anomalies of cerebrovascular system ICD10 Q28.2 Arteriovenous malformation of cerebral vessels

CLINICAL PEARLS

• Pregnant patients with AVMs should avoid strenuous and painful labor; epidural and/or elective C-section is recommended. In the setting of intracranial hemorrhage, pregnant patients receive the same neurosurgical management as the nonpregnant patient. Anesthetic techniques in the pregnant patient should include considerations for the developing fetus; avoiding certain medications such as mannitol (to avoid fetal dehydration, instead use a loop diuretic such as furosemide), beta-blockers (to minimize fetal bradycardia, use a combined beta and alpha blocker such as labetalol), sodium nitroprusside (fetal cyanide toxicity), and benzodiazepines (although only long-term use has possible teratogenic effect). Additionally, limit profound hyperventilation so as not to impair fetal oxygen delivery from alkalosis/hyperventilation-induced umbilical artery constriction, decreased uteroplacental perfusion, and by a leftward shift of the maternal oxygen–hemoglobin dissociation curve.

CEREBRAL BLOOD FLOW Jayson T. Maynes, MD, PhD Ivan M. Kangrga, MD, PhD

BASICS DESCRIPTION

• Although the brain comprises only 2% of the body’s mass, it accounts for ∼20% of the body’s metabolic requirements and receives 14% of the cardiac output. • Regional differences of cerebral blood flow (CBF) exist and reflect the metabolic requirements (cerebral metabolic rate of oxygen, CMRO2). CBF in: – Gray matter is 80 mL/100 g/min (CMRO2 of 6 mL/100 g/min).

– White matter is 20 mL/100 g/min (CMRO2 of 2 mL/100 g/min).

– Global average is 50 mL/100 g/min (CMRO2 of 3.2 mL/100 g/min).

• Demographics and CBF. In addition, CBF is higher in females than males and also decreases with age. PHYSIOLOGY PRINCIPLES

• The brain requires a constant supply of a substrate and oxidizer in order to meet the high metabolic requirements. – Glucose is the main metabolic precursor with a consumption of ∼5 mg/100 g/min; ∼90% is metabolized aerobically. When unavailable, secondary metabolic precursors include acetoacetate and beta-hydroxybutyrate. – There is no adenosine triphosphate (ATP) storage mechanism in the brain. Thus, in the event that the oxygen supply is lost, ATP levels will fall to zero within 7 minutes. – 40% of the brain’s energy is used for basal function (membrane potential, “housekeeping" activities) and the remainder 60% is used for functional activity (signal transmission). • Cerebral oxygen extraction is high compared to the systemic circulation. Hemoglobin saturations measured at the jugular vein (SjO2) range from 45–60%, compared to normal mixed venous saturations (SvO2) of 55–70%.

• Regional flow. CBF lacks global control. Instead, areas of the brain act in an independent fashion to control flow via heterogeneous and homeostatic control mechanisms. Homeostatic mechanisms of CBF control include metabolism, temperature, metabolic products, PaCO2, PaO2, blood viscosity, and autoregulation.

– Metabolism. Blood flow-metabolism coupling is the most important mediator of the cerebral circulation and is maintained during sleep and general anesthesia. The CMRO2

varies regionally in the brain. Under normal circumstances, its main determinants are sleep or wakefulness, temperature, age, and degree of neuronal activity (e.g., seizures). – Hypothermia reduces CMRO2 (and therefore CBF) by 5–7% for every degree Celsius drop

in body temperature (functional and basal energy requirements). The Q10 for CBF in

humans is 2 (represents the factor by which the reaction rate decreases when the temperature is decreased by ten degrees; it is a unitless quantity). Complete suppression of metabolic activity occurs at 18–20%C. – Metabolic products. Mediators of cerebral vasodilation and flow-metabolism coupling include glutamate (indirectly by causing release of vasodilators, a feed-forward mechanism), arachidonate derivatives, nitric oxide (NO), prostaglandin E2 (PGE2) adenosine, potassium, vasoactive intestinal peptide, lactate, and carbon dioxide (CO2).

– PaCO2. CO2 crosses the blood–brain barrier (BBB) and changes the pH of the CSF. CBF

increases linearly by 2–4% (1–2 mL/100 g/min) per 1 mm Hg increase in PaCO2 (when

the PaCO2 is in the range of 25–75 mm Hg). The change begins within seconds, and fully

equilibrates within 2 minutes. Conditions that cause a reduction in CO2 reactivity include

severe carotid artery stenosis, head injury, subarachnoid hemorrhage, hypotension, cardiac failure, female gender, and age (>40 years). Acids and protons themselves cannot cross the BBB (1,2)[A]. – PaO2. A PaO2 <60 mm Hg will increase CBF and takes 6 minutes to equilibrate (2)[A].

– Viscosity. Blood viscosity is primarily determined by hematocrit and temperature. As viscosity decreases, the CBF increases due to changes in blood rheology. The effect that this has on the microvascular circulation is not consistent and depends on local factors. Therefore, the generalization that a lower hematocrit improves microcirculatory flow cannot be made. Additionally, a lower viscosity may increase intracranial pressure (ICP). – CBF autoregulation. Under normal conditions, there is minimal change in the CBF with mean arterial pressure (MAP) changes between 60 and 160 mm Hg. Both arterioles (smooth muscle in vessel wall) and capillaries (pericytes that encircle the capillary) dilate or constrict in response to perfusion pressure, in order to maintain a constant blood flow. However, larger arteries and the venous system do not play a role in dynamic flow changes. It should be noted that there is significant individual variation in the range of autoregulation, based on a person’s baseline BP. • Global and regional blood flow can be measured by nitrous oxide washout and Xenon CT scanning/Xe clearance. Neither is done routinely.

ANATOMY

• Generally, branches of the common carotid arteries supply the cerebrum and branches of the vertebral arteries supply the cerebellum. • All areas supplied by the carotid arteries have good collateral circulation except for the middle cerebral artery. This area is most prone to ischemia. • The classical Circle of Willis for collateral circulation is present in only 50% of people. • The superior sympathetic ganglion provides sympathetic stimulation to the cerebral vasculature, and plays a role in cerebral vasospasm following injury and stroke.

DISEASE/PATHOPHYSIOLOGY

• The fixed volume of the intracranial vault consists of brain tissue (80%), blood (12%), and

CSF (8%). ICPs above 30 mm Hg generally produce pathological changes in CBF (with 15 mm Hg being defined as an elevated ICP). CBF at this point becomes strictly flow dependent (entirely reliant on the MAP being greater than the ICP) (3)[A]. • Cushing’s response: A physiologic phenomenon resulting from increased ICP and subsequent cerebral ischemia. It consists of – Hypertension (to increase the cerebral perfusion pressure, or CPP) – Bradycardia (an inappropriate reflex to the hypertension) – Irregular respirations (from pressure on the brain stem); not always observable • Cerebral autoregulation is impaired by – Trauma or traumatic brain injury – Hypoxemia – Hypercapnia (PaCO2 >60 mm Hg) – High-dose volatile anesthetics – Subarachnoid hemorrhage – Ischemic cerebrovascular disease • Ischemia. Because of regional differences, CBF in one area does not correlate with blood flow in another ischemia-prone area. – Normal CPP is 80–100 mm Hg in adults. – CPP <50 mm Hg manifests as EEG slowing. – CPP <25–40 mm Hg will produce a flat EEG. – CBF <15–20 mL/100 g/min shows an isoelectric EEG signal. – CBF <5 mL/100 g/min produces irreversible damage (1)[A]. • Moyamoya: Creation of a web of collateral vessels to deeper brain structures as a result of longstanding stenosis/malformation of the internal carotid arteries. Pathology of the blood vessels shows intimal hyperplasia and elastic fiber formation with sparing of the media and adventitia. This is likely from an elevation of basic fibroblast growth factor. The Moya-Moya regions have decreased responsiveness to CO2 and are dependent on CPP alone to avoid underperfusion (ischemia) and overperfusion (rupture). Brain areas around the stenosed vessels show a decreased CMRO2 and regional blood flow with an increased oxygen

extraction ratio (signs of inadequate blood supply). There is a bimodal age of presentation in the 1st and 4th decades of life. Pediatric patients commonly present with signs of ischemia (∼80%), whereas adults predominantly present with a rupture (40–65%, usually basal ganglia). Symptoms may be elicited by maneuvers that lower the PaCO2, causing

vasoconstriction and focal ischemia (coughing, crying, straining, hyperventilation). During anesthesia, it is vitally important to preserve blood flow to areas with a tenuous supply. This is achieved with preoperative volume restitution (preadmittance with IV fluids), avoidance of cerebral vasoconstriction (avoid crying and hyperventilation before induction), intraoperative EEG with or without cerebral oximetry, frequent blood gases to avoid both hypocapnea (watershed ischemia), and hypercapnea (steal of blood from the Moya-Moya regions by dilated cerebral vessels). Efforts should be made to minimize intraoperative CMRO2 (avoid pain intraoperatively with adequate opiates/anesthesia and avoid hyperthermia). Steal may also occur with the return to normocarbia after a period of hypocarbia and the EEG may take time to normalize (3,4)[A and C].

• Carotid stenosis/carotid endarterectomy (CEA). Stenosis can impair CBF and perfusion pressures, resulting in syncopal episodes, ischemia, and stroke; repair is undertaken in order to restore flow. Intraoperatively, the MAP (and therefore the CPP) can change rapidly with increases and decreases in pressures, catecholamine release from manipulation of the carotid sinus, and bradycardia from vagus nerve clamping. Postoperatively, hyperperfusion syndrome may result; its etiology is not clear, but is related to postoperative hypertension to previously underperfused areas and usually does not occur until several hours after surgery. • Ruptured cerebral aneurysms/subarachnoid hemorrhage. Inadequate regional blood flow or ischemia is experienced in the area of the aneurysm. Extravascular hemoglobin can cause cerebral vasospasm, exacerbating the ischemia. • Vasospasm can be treated with nimodipine or “Triple H Therapy”: Hemodilution, hypervolemia, and hypertension.

PERIOPERATIVE RELEVANCE

• Anesthetic agents decrease the neuronal functional energy expenditure, but do not change the basal energy expenditure. Thus, all volatile agents, propofol, and barbiturates can reduce the CMRO2 to a flat EEG reflecting electrical silence, but can act no further (unlike

hypothermia). – Regional differences. Propofol and barbiturates produce a larger overall reduction in CMRO2 than inhalational anesthetics; this is of unknown benefit. Additionally, this

decrease is not uniform across the brain; propofol and barbiturates produce a larger reduction in the cerebellum and deep structures, whereas volatile agents produce a greater reduction in the neocortex. – Direct effects. Propofol and barbiturates have minimal effect on cerebrovascular tone but may decrease the CPP by lowering the MAP. Propofol has slight cerebral vasoconstrictive properties. Opiates have the least direct effect on CBF (if the MAP is maintained); exceptions include the ability of alfentanil and normeperidine to induce seizure foci, resulting in a focal increase in CMRO2 in the seizure area. Ketamine increases CMRO2 in

focal areas and therefore CBF. It also dilates cerebral vasculature, increasing the ICP, and can induce seizure activity. – Autoregulation. Volatile agents dilate the cerebral vessels but do not abolish autoregulation. The effect is transitory and, within 5 hours, blood flow returns to normal. • CBF in chronic hypertensives. The autoregulation region is right-shifted and vessels are narrower, thus patients can experience ischemia at moderately low blood pressures compared to normotensives. Perioperatively, patients should have their BP maintained at a higher pressure to compensate and avoid ischemia. Generally, a change of less than 30% from baseline is recommended. • Perioperative stroke. The rate of postoperative stroke is small (0.08–0.4%) but is slightly higher in patients with known cerebrovascular disease (0.4–3.3%). It is highest in patients having open cardiac surgery (4%). Documenting preoperative neurological deficits is imperative in identifying brain regions susceptible to ischemia, to document changes postoperatively, and to identify patients at risk of difficult extubations (cranial nerve involvement or cognitive problems). The mortality after postoperative stroke is high (26%). • EEG. The absolute EEG frequencies are less important than sudden changes or trends during

intraoperative occurrences or surgical events (e.g., carotid clamping during a CEA in order to decide whether to create an arterial shunt). • Cerebral vessel anatomy. For relevant surgeries, the patency of the Circle of Willis and presence of collateral blood flow can be tested preoperatively using cerebral angiography. This may aid with estimating the chances of cerebral ischemia.

EQUATIONS

CPP = MAP – (CVP or ICP); the greater of the two values is utilized. CPP is cerebral perfusion pressure, MAP is mean arterial pressure, CVP is central venous pressure, and ICP is intracranial pressure.

REFERENCES

1. Curley G, Laffey JG, Kavanagh BP. Bench-to-bedside review: Carbon dioxide. Crit Care. 2010;14(2):220–226. 2. Curley G, Kavanagh BP, Laffey JG. Hypocapnia and the injured brain: More harm than benefit. Crit Care Med. 2010;38(5):1348–1359. 3. Vavilala M, Lee L, Lam, AM. Cerebral blood flow and vascular physiology. Anesthesiology Clin N Am. 2002;20:247–264. 4. Parray T, Martin TW, Siddiqui S. Moyamoya disease: A review of the disease and anesthetic management. J Neurosurg Anesthesiol Epub ahead of print.

ADDITIONAL READING

• Carney NA, Ghajar J. Guidelines for the management of severe traumatic brain injury. J Neurotrauma. 2007;24(Suppl 1):S1–2. • Patel PM, Drummond JC. “Cerebral physiology and the effects of anesthetics and techniques”, in Miller’s anesthesia Sixth Edition, ed. D. Miller (Philadelphia: Elsevier, 2005) pp. 813–857.

See Also (Topic, Algorithm, Electronic Media Element) • Cerebral metabolic rate • Carotid endarterectomy • Electroencephalogram (EEG) • Craniotomy, cerebral aneurysm clipping • Circle of Willis • Postoperative stroke

CLINICAL PEARLS

• Intraoperative shunting of blood may be done to increase CBF in cases such as CEA and in the repair of a proximal thoracic aortic aneurysm. • Desflurane and sevoflurane maintain flow metabolism coupling to a higher degree than isoflurane. • Propofol has a slight vasoconstrictive property and will not increase cerebral blood volume

or ICP but may lower the CPP secondary to lowering of the systemic BP. • Dynamic cerebral autoregulation can be tested by inflating bilateral thigh BP cuffs for 3 minutes and measuring CBF changes with transcranial Doppler while quickly deflating both cuffs. • Cerebral vasospasm can be partially avoided with nimodipine, but if the vasospasm has already occurred, nimodipine will be less effective. • Ketamine should be avoided in any patient with an increased ICP, increased intraocular pressure, or a prior history of seizures.

CEREBRAL EMBOLIZATION Carsten Nadjat-Haiem, MD Keren Ziv, MD

BASICS DESCRIPTION General

• Cerebral embolization is performed in the neuroradiology suite for the treatment of cerebral aneurysms, arteriovenous malformations (AVM), and in preparation for intracranial tumor resections. • Patients presenting for embolization range from being very healthy with unruptured aneurysms (Hunt and Hess classification grade 1, survival >70%) to comatose and moribund (Hunt and Hess grade 5, survival <10%). • These procedures can be lengthy and uncomfortable for patients and hence will either require monitored anesthesia care or general anesthesia. • Vascular sheaths are introduced into the femoral arteries, through which catheters are passed. Fluoroscopy is used to advance and position the catheters near the level of the aneurysm. Microcatheters with detachable coils are then threaded through the catheter and deployed at the site of the aneurysm. Coils are typically made of soft platinum wires with a diameter smaller than a strand of hair; they come in varying diameters and lengths. They are flexible and can conform to the aneurysm shape. • The body eventually forms blood clots around the coils and blocks blood flow into the bulge or passageway to keep the vessel from rupturing or leaking; this decreases transluminal pressure against the aneurysmal wall. • Coils are not the only choice for embolization. Cyanoacrylates, onyx embolic material, gelfoam, polyvinyl alcohol, and others are also used. Position

• Supine • Bilateral groins are prepped and draped for vascular access. • Limited access to the patient due to fluoroscopy equipment (particularly if 3D images are obtained). Incision

Bilateral percutaneous punctures are made in the groin to access femoral vessels. Approximate Time

Simple cases will be accomplished in 1–2 hours, while complex cases can take many hours. EBL Expected

• Usually minimal, on the order of 50–100 cc.

• In the event of aneurysm or AVM rupture during the procedure, there may be some blood loss, which has little hemodynamic consequences, but dire effects on the CNS. This may require emergent ventricular drain placement or even craniotomy for evacuation of hematoma and clipping of the aneurysm or AVM. • There is a small risk of hidden retroperitoneal hematomas, which can become hemodynamically significant.

Hospital Stay

Patients are typically discharged home on postoperative day one after coiling for unruptured lesions. Others may require multiple-day hospitalizations as dictated by the patient’s condition. Special Equipment for Surgery

• Comprehensive fluoroscopy equipment with 3D capabilities and computer processing • IV contrast dye • Detachable coils or other embolization material

EPIDEMIOLOGY Incidence

• Incidence of subarachnoid hemorrhage (SAH) is 9 per 100,000 people annually. • Up to 85% of cases of spontaneous SAH are due to ruptured aneurysms. • Other causes of SAH are AVMs (~10%), cerebral hemorrhage (~10%), and others (e.g., tumors). • Risk increases with age, family history, hypertension, heavy alcohol consumption, and smoking • Most hemorrhages are from small aneurysms, although risk of rupture increases with increasing size.

Prevalence

About 1–2% of the population has at least one cerebral aneurysm. Morbidity

• If the early course after aneurysm rupture is survived, 25% of patients will have significant restrictions in their lifestyle, and only 20% will have no residual symptoms. • Other problems include long-term cognitive impairment, depression, fatigue, headache, PTSD, and hypopituitarism.

Mortality

• Following a SAH, mortality can approach 50%. • Unruptured aneurysms or AVMs who undergo uncomplicated procedures, generally do very well.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• During induction of anesthesia and stimulating parts of the procedure, tight BP control is essential to prevent rupture or rebleeding.

• For ruptured aneurysms, prevention of vasospasm and management of increased intracranial pressure (ICP). • Limited access to the patient requires optimizing monitor location and having adequate extensions for the breathing circuit and other catheters.

PREOPERATIVE ASSESSMENT SYMPTOMS

For hemorrhage: increased ICP such as headache, nausea, vomiting, altered sensorium, or focal neurologic finding. History

• Healthy patients for elective coiling need no special workup. • A detailed history as to the presence of hypertension is sought. • Contrast or shellfish allergy is elicited given the large amounts of contrast used. • Heparin and protamine allergies should be noted.

Signs/Physical Exam

A thorough neurologic exam needs to be performed to assess the baseline status of the patient so it can be compared to the postprocedure exam. In this fashion, subtle changes can be picked up; allowing for further diagnostics and therapeutics to be pursued in a timely fashion. MEDICATIONS

Patients presenting to the interventional radiology suite for urgent embolization may have been given mannitol, furosemide, or 3% saline to manage intracranial hypertension; calcium channel blockers to prevent vasospasm; other medications to control BP. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hg/Hct to assess hemodilution during triple H therapy (hypertension, hemodilution, hypervolemia). • Chemistry panel to assess for cerebral salt-wasting (hyponatremia and hypokalemia) due to the release of brain and atrial natriuretic hormone and SIADH. • SAH can produce EKG changes including QT prolongation, Q waves, cardiac dysrhythmias, and signs consistent with acute ischemia.

CONCOMITANT ORGAN DYSFUNCTION

• Rhythm disturbances will occur in up to 90% of patients with SAH. • A small percentage of patients with SAH will develop ischemic cardiomyopathy due to vasospasm and high catecholamine state. This needs to be addressed in the same manner as ischemia from coronary artery disease secondary to arthrosclerosis would be treated. Usually this ischemia is reversible and patients recover.

TREATMENT

PREOPERATIVE PREPARATION Premedications

• Healthy patients may be given premedication in usual fashion, with the caveat that heavy premedication and short cases may lead to delayed emergence and neurological assessment. • Patients with altered sensorium or with increased ICP should be premedicated very carefully, if at all, as small changes in CO2 tension can lead to large changes in ICP and obtundation.

Special Concerns for Informed Consent

Patients need to understand that there may be a need for prolonged intubation and the possibility for emergent craniotomy. Antibiotics/Common Organisms Usually no antibiotics are given. INTRAOPERATIVE CARE Choice of Anesthesia

• Local only, monitored anesthesia care, or general anesthesia may be appropriate. • Local cases may be appropriate for otherwise healthy and very motivated patients with minimal risk for cerebral ischemia requiring emergent intubation. • Monitored anesthesia care, again, should be reserved for healthy motivated patients. Sedation should be kept very light as to allow for patient communication and cooperation. • General anesthesia (with endotracheal intubation) is chosen in most cases. Benefits include a motionless field, full airway control, control of hemodynamics and ICP, and control during complications (acute rupture, induction of barbiturate coma, treatment of seizures, and emergent craniotomy).

Monitors

• Standard ASA monitors • Foley catheter • There should be a low threshold for placing an arterial line in patients with SAH from a ruptured aneurysm or AVM; if difficult to access, the operating physician can often provide access via the groin line. • EEG monitoring and evoked potentials are not the standard of care, but should be considered in cases of giant and wide neck aneurysms, aneurysm in close proximity to other vessels, high ICP, large SAH, or who are otherwise at risk for cerebral ischemia.

Induction/Airway Management

• Management of ICP, BP, cerebral perfusion pressure (CPP), and the airway are the main concerns during induction. • Patients with unruptured aneurysms and AVMs rarely have high ICP. Maintaining a stable BP with minimal variation is more important than an absolute number. Patients with recently ruptured aneurysms or AVMs should have their BP controlled at, or slightly below, normal levels to avoid rebleeding. If the ICP is increased, a drop in BP can cause CPP to

become marginal. Intracranial hypertension may be controlled with mannitol, hyperventilation, furosemide, and decreasing or discontinuing volatile anesthetics (convert to a propofol, dexmedetomidine, and/or opioid technique). • Patients at risk for vasospasm on “triple H (hypertension, hemodilution, hypervolemia)" therapy need to have their BP maintained in the high normal range to avoid cerebral ischemia. This is accomplished with a combination of pressors and volume.

Maintenance

• Unless ICP cannot be controlled with the methods described, a balanced anesthetic with low levels of volatile anesthetics can be employed. • There is no evidence that any particular anesthetic is superior to another for uncomplicated cases. • Movement must be avoided utilizing either deep anesthesia or paralysis, especially during critical coil positioning and deployment. Coil positioning and deployment is usually not painful, but when work is performed close to the dura, thalamus, or certain parts of the brainstem (e.g., during AVM embolization), the patient may move. • Coagulation management with heparin and other agents may be required to prevent intraoperative thromboembolic events; this may need to be reversed at the conclusion of the case. Protamine reversal is often done with a small “test dose” to assess for allergic or anaphylactic reactions followed by slow titration to avoid hypotension.

Extubation/Emergence

• Naturally, emergence should be smooth. • Endotracheal lidocaine may be administered at the beginning of the case during laryngoscopy. Alternatively, IV lidocaine may be given at the end to reduce tracheal reflexes. • Aggressive multimodal emesis prophylaxis.

POSTOPERATIVE CARE BED ACUITY

Almost all patients, even those presenting electively, will require overnight ICU or step-down care for frequent neurological assessments. Continued higher level of care is dictated by the patients’ condition. ANALGESIA

• Usually, patients will have very little postoperative pain. Local anesthesia at the site of puncture should be administered intraoperatively. • Some patients (especially those with AVMs) may experience strong headaches due to venous congestion. They can be given small doses of opioids. Head elevation may also help.

COMPLICATIONS

• Rare (about 3%) and include hemorrhage (aneurysm perforation, vessel injury, dissection) or occlusion (thromboembolic, coil displacement, vasospasm) • Contrast reaction/nephropathy

• Hemorrhage at the puncture site • Retroperitoneal hematoma • Infection

PROGNOSIS

• The International Subarachnoid Aneurysm Trial has shown that endovascular coiling of simple aneurysms is superior to surgical clipping if measured as survival and development of seizures at 1 year, but the risk of rebleeding is higher in the coiling group. • Even for complex aneurysms, aneurysm coiling is at least as efficacious as clipping.

REFERENCES

1. Molyneux A, Kerr R, Stratton I, et al. International subarachnoid aneurysm trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: A randomised trial. Lancet. 2002;360:1267–1274. 2. Van der Schaaf I, Algra A, Werner M, et al. Endovascular coiling versus neurosurgical clipping for patients with aneurysmal subarachnoid hemorrhage. Cochrane Database Sys Rev. 2005: CD003085. 3. Lui AY, Lopez JR, Do HM, et al. Neurophysiological monitoring in the endovascular therapy of aneurysms. Anesth Analg. 2007;105:887–888.

ADDITIONAL READING

• Nadjat-Haiem C, Ziv K, Osborn I. Anesthesia for cerebrovascular procedures in Interventional Neuroradiology. IAC. 2009;47(2):29–43. • Varma MK, Price K, Jayakrishnan V, et al. Anesthetic considerations for interventional radiology. Br J Anesth. 2007;25:391–412.

See Also (Topic, Algorithm, Electronic Media Element) • Craniotomy for cerebral aneurysm clipping • Craniotomy for intracranial hemorrhage

CLINICAL PEARLS

• Use same standards and vigilance as during a craniotomy. Be prepared to look for signs of hemorrhage (e.g., Cushing’s response) and be prepared to change venue (CT scanner, operating room). • Avoid movement during critical parts of the procedure and be aware of what the procedurist is doing. Good communication between the neurointerventionalist and anesthesiologist is crucial, especially if complications arise (prompt decisions can be made regarding further treatment).

CEREBRAL METABOLIC RATE Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Cerebral metabolic rate of oxygen (CMRO2) is described as the milliliters of oxygen

consumed by 100 g of brain tissue per minute. • Local differences exist for the CMRO2 (gray versus white matter, type of cell). In the adult, the averaged value over all areas is 3–3.5 mL/100 g/minute. • The neuroanesthetist must balance the CMRO2 with oxygen delivery. However, despite the

importance, there are no readily available techniques within the operating room that can directly measure tissue oxygen metabolism.

PHYSIOLOGY PRINCIPLES

• The adult human brain weighs ∼2% of the total body weight. However, it – Receives ∼12–15% of the cardiac output; and is considered a high perfusion organ. – Comprises ∼20% of total body oxygen consumption. This high rate is required primarily for the maintenance of depolarization and repolarization activity as well as for cellular homeostasis. • CMRO2 and cerebral blood flow (CBF) are “coupled.” Increases in oxygen consumption are met by an increase in blood flow. The mechanism is not completely understood; however, it is believed that local factors and nitric oxide (NO) contribute to changes in vascular tone and CBF based on electrical and metabolic oxygen demands. – Normal CBF is ∼45–55 mL/100 g/minute and autoregulation maintains a relatively constant CBF over a wide range of mean arterial pressures (MAPs), between 70 and 150 mm Hg. – Increases in CMRO2 result in parallel increases in CBF, whereas decreases in CMRO2 result

in parallel decreases in CBF. – Consequently, increases in neuronal activity result in a “superfluous” increase in CBF compared to the CMRO2 (provides a cushion) (1).

• Regional differences of CMRO2 (and hence CBF) are as follows (2):

– Gray matter is four times that of white matter. – Neurons are greater than glial cells. – Lowest in the spinal cord and increases cephaladly through the medulla, midbrain, thalamus, cerebellum, and cerebral cortex. • Factors affecting CMRO2 (and hence CBF).

– Sleep. Non-rapid eye movement (Stages 2 and 3) is associated with a 23% reduction across the entire brain (regional variations exist). However, certain areas (basal forebrain, hypothalamus, amygdala, hippocampus) have an increase in glucose utilization likely

from homeostatic regulation and mnemonic processing. – Aging results in neuronal loss and can also progressively lower CMRO2 (3). ANATOMY

• Gray matter comprises ∼40% of the brain’s mass and consists of neuronal cell bodies, dendrites, and glial cells. Mostly present in the outer portions. • White matter comprises ∼60% of the brain’s mass and consists of myelinated axons and is mostly present in the inner portions. • Seizure activity describes uncontrolled and chaotic electrical activity that is accompanied by significant increases in CMRO2. With status epilepticus, values can increase by 200–300%

(4). • Oxygen delivery – Decreases that are secondary to impaired CBF (stroke, hypotension) are accompanied by decreased glucose delivery and increased partial pressure of carbon dioxide (PaCO2). Initially, the brain tissue increases oxygen extraction to compensate, and CMRO2 remains

stable. However, when the reduction in CBF exhausts the compensatory increase in oxygen extraction, the CMRO2 decreases.

– Decreased blood oxygen content is accompanied by the normal delivery of glucose and does not affect carbon dioxide removal. Normal arterial partial pressures are ∼100 mm Hg. At values of 30 mm Hg, there is a significant decrease in the CMRO2 that is

accompanied by a ∼50% increase in CBF (5). • Carbon dioxide. Increases in the PaCO2 result in vasodilation and increased CBF (pH mediated mechanism). However, its effects on the CMRO2 are poorly understood and lack

consensus. At this time, it is believed that mild increases appear to have a negligible effect on global CMRO2.

PERIOPERATIVE RELEVANCE

• The neuroanesthetist is often called on to manipulate the CMRO2 and optimize oxygenation.

– Decreases in electrical activity can be attained with both IV and volatile agents. The electroencephalogram may be utilized to assess electrical activity (not cellular homeostasis). The term burst suppression describes a periodic pattern of high-amplitude complexes that are interspersed by low-voltage amplitude complexes. This represents a state of maximal electrical activity suppression (recall that this comprises the majority of CMRO2) (6). – Cellular homeostasis (“basic housekeeping”) may be decreased by lowering the temperature. Hypothermia lowers the CMRO2 that is associated with providing energy

(e.g., adenosine triphosphate [ATP] to maintain transmembrane ion gradients) that is essential for neuronal viability and other basic functions of cellular upkeep (e.g., protein synthesis). For each degree celsius decrease, there is a corresponding CMRO2 decrease of ∼7%. To that extent, deep circulatory arrest can theoretically approach a CMRO2 of zero.

• IV medications, in general, maintain coupling of CMRO2 and CBF.

– Barbiturates. Dose-dependent reduction in CBF and CMRO2. Tolerance to this effect can

develop rapidly. Animal studies have demonstrated improved outcome for focal, but not global, ischemia. – Propofol. Appears to have a similar dose-dependent reduction in CBF and CMRO2 as barbiturates. Its shorter duration of action compared to barbiturates can decrease the need for postoperative intubation and delays in performing a neurological exam. – Etomidate. Appears to have a similar profile to barbiturates. Because it maintains MAP well, it can effectively reduce intracranial pressure (ICP) without reductions in cerebral perfusion pressures (CPP) with tumors and closed head injuries (CHI). It is not routinely used to induce or maintain burst suppression, however, due to its ability to cause adrenocortical suppression and renal injury with repeat, routine, or continuous use. – Ketamine. The only IV anesthetic agent that can cause an increase in the CMRO2 and

hence CBF (elevation in ICP). These effects can be blunted by coadministration of volatile agents or benzodiazepines. – Benzodiazepines. Decreases CMRO2 and CBF. – Flumazenil (in some studies) has been shown to increase CBF and ICP. – Lidocaine can decrease CMRO2 in a dose-dependent fashion. A bolus dose has been

advocated as an adjunct for acute elevated ICP. However, CNS toxicity can cause seizures that will increase the CMRO2.

– Narcotics. It appears that CBF and CMRO2 are relatively unaffected. However, the information has inconsistencies and varies depending on the narcotic. When an effect was found, usually it showed a decrease in CMRO2 and CBF.

– Epinephrine and norepinephrine. Increase CMRO2 and CBF regardless of whether or not

there is an intact blood–brain barrier (BBB). – Dobutamine. Can increase CMRO2 and CBF by up to 30%.

– Beta-blockers. Studies show that they appear to reduce or have no effect on CMRO2 or

CBF. – Alpha 2-agonists (dexmedetomidine). Reduces CBF with no effect on CMRO2.

– Nondepolarizing muscle relaxants. Do not directly affect CMRO2. However, the histamine

release associated with atracurium can increase ICP. – Succinylcholine. Does not directly affect CMRO2. However, histamine release can cause a

rapid increase in ICP. • Volatile agents decrease the CMRO2; however, CBF does not decrease in parallel; this is

known as “uncoupling.” The cerebral vasculature vasodilates due to smooth muscle relaxation in response to the volatile agent. This increases the CBF to CMRO2 ratio with

resultant “luxury” perfusion. – Order of CMRO2 suppression (measured in terms of equal MAC concentrations): Isoflurane, enflurane, desflurane, sevoflurane>halothane.

– Order of vasodilating potency: Halothane>>enflurane>isoflurane = sevoflurane = desflurane. After initially increasing the CBF, there is a substantial fall in CBF until a steady state is reached (usually after 2.5–5 hours after exposure). – Therapeutic use: Decreases in CMRO2 can develop quickly.

– Carbon dioxide responsiveness remains well maintained. • Nitrous oxide (N2O). Results have been mixed; however, it is generally accepted that the CMRO2, CBF, and ICP increase, likely from sympatho-adrenal-stimulating effects.

GRAPHS/FIGURES See Table See Table

REFERENCES

1. Uludag K, Dubowitz DJ, Yoder EJ, et al. Coupling of cerebral blood flow and oxygen consumption during physiological activation and deactivation measured with fMRI. Neuroimag. 2004;23:148–155. 2. Jain V, Langham MC, Floyd TF, et al. Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapnia. J Cereb Blood Flow Metab. 2011;31(7):1504–1512. 3. Nofzinger EA, Buysse DJ, Miewald JM, et al. Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking. Brain. 2002;125(Pt 5):1105– 1115. 4. Ingvar M. Cerebral blood flow and metabolic rate during seizures. Relationship to epileptic brain damage. Ann N Y Acad Sci. 1986;462:194–206. 5. An H, Liu Q, Chen Y, Lin W, et al. Evaluation of MR-derived cerebral oxygen metabolic index in experimental hyperoxic hypercapnia, hypoxia, and ischemia. Stroke. 2009;40:2165–2172. 6. Nemoto EM, Klementavicius R, Melick JA, et al. Suppression of cerebral metabolic rate for oxygen (CMRO2) by mild hypothermia compared with thiopental. J Neurosurg Anesthesiol. 1996;8(1):52–59.

• Intracranial hypertension • Cerebral blood flow • Burst suppression

CLINICAL PEARLS

• Increases in CMRO2 can have detrimental effects, possibly resulting in intracranial

hypertension from increased CBF as well as ischemia from an imbalance in oxygen supply and demand. • Most IV anesthetics cause a decrease in both CBF and CMRO2, except ketamine that can cause an increase in both.

• Volatile agents “uncouple” CBF and CMRO2. In other words, while CMR decreases, CBF does not (can increase or remain the same). • For every degree (celsius) decrease, the CMRO2 falls ∼6–7%.

CEREBRAL PALSY

Marc A. Logarta, MD, DABA, FANZCA

BASICS DESCRIPTION

• Cerebral palsy (CP) is a term used to describe a large and diverse group of neurological disorders that result from injury to the developing fetal or infant nervous system. • It is associated with varying degrees of motor, sensory, and intellectual impairment. In mild cases, the patient can be almost completely functional and in severe cases patients can have profound morbidity and mortality even in childhood. • Nonprogressive condition; does not have an evolving neurologic clinical deterioration.

EPIDEMIOLOGY Prevalence

1:450 live births in developed countries Prevalence

1:350 children and adults in the US Morbidity

Although CP is often manifested as problems with posture and movement, the more severe forms affect neurologic, respiratory, GI, musculoskeletal, and genitourinary systems. ETIOLOGY/RISK FACTORS

• Congenital CP (80% of cases) – Prematurity (10 to 50-fold increase) – Neonatal asphyxia – Male gender – Chorioamnionitis – Preeclampsia – Peripartum hemorrhage – Advanced maternal age – Multiparous birth – Initial low Apgar score – Prenatal infection (toxoplasmosis, rubella, cytomegalovirus, herpes) – Vascular maldevelopments – Metabolic disorders – Intrauterine growth retardation – Trauma to fetus – Breech birth – Maternal hypothyroidism

– Fetal alcohol syndrome • Acquired CP (20%) within first 2 years of life – Intracerebral hemorrhage – Bacterial meningitis – Hyperbilirubinemia – Viral encephalitis – Brain injury – Neonatal seizures

PHYSIOLOGY/PATHOPHYSIOLOGY

• Clinical presentation may result from neurologic injury that occurs in the prenatal, perinatal, or postnatal periods. The injury may be due to toxins, infections, hypoxia, vascular insufficiency, trauma, or complications associated with prematurity. • Injury may occur at different points in brain development, therefore resulting in a wide spectrum of clinical presentations. • CP due to prematurity is most likely associated with the physical stress that the premature neonate brain is unable to compensate for. This results in cerebral white matter hypoperfusion, which can lead to varying degrees in subependymal and germinal matrix hemorrhage and/or leukomalacia. Because these areas carry fibers responsible for motor control to the lower extremities, the patient suffers from lower extremity weakness and spasticity. • If hemorrhagic lesions extend outward from the lateral ventricles toward the descending fibers of the motor cortex (centrum semiovale and corona radiata), then the upper extremities will be affected along with the lower extremities. • CP due to hyperbilirubinemia or hypoxic ischemic injury perinatally result in extrapyramidal signs often associated with hypertonicity. • In summary there is no one cause of CP as is outlined in the risk factors above, and most cases are likely to have multifactorial causes. By definition, CP is a nonprogressive disorder in which the injury has occurred and does not have an evolving neurologic clinical deterioration.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess severity of multiorgan disease • Assess the patient’s level of cooperation and cognition. • Optimize pulmonary function, minimize chance of aspiration • Return to normal regimen of anticonvulsant and antispasmodic medications as soon as possible so as to avoid adverse events such as withdrawal symptoms and seizures.

PREOPERATIVE ASSESSMENT SYMPTOMS

Cardiopulmonary symptomatology is difficult to evaluate because these patients will frequently be immobile, but may have ischemic heart disease, pulmonary hypertension, and cor pulmonale.

History

• Up to 70% may have intellectual impairment. • Enlist the help of the parent/guardian to take a thorough history including an evaluation of previous anesthetics – many of these patients will have had frequent surgical procedures. • Many patients will have an ASA classification of III or more due to other comorbid conditions. Assess the multiple organ systems involved. • Assess fluid status and hydration • Assess drug regimen and efficacy • Inquire about intrathecal baclofen pump • Assess level of cooperation • Inquire about chronic pain conditions

Signs/Physical Exam

• Muscle contractures, spasticity, and sometimes hypotonia • Abnormal neck or truncal tone • Asymmetric posture, strength, or gait • Temporomandibular joint (TMJ) dislocation • Scoliosis

MEDICATIONS

• Baclofen (oral or via intrathecal pump): Used to decrease spasticity, especially in lower extremities. Withdrawal symptoms can include confusion, painful muscle spasms, seizures, and hemodynamic instability. • Anticonvulsants: May be on multiple medications for chronic seizure disorder (can increase metabolism of anesthetic drugs). • Botulinum: Injections are often used to decrease muscle spasticity and progression to contractures. Botulinum can also be used to reduce drooling associated with CP. • Patients may also be on chronic regimens of antidepressants, antibiotics (for recurrent infections), and analgesics. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Chest Radiograph (CXR) (pneumonia, cardiomegaly, and congestive heart failure) • Electrocardiogram (right heart failure, ischemic heart disease) • Complete blood count, electrolytes, urea, and creatinine

CONCOMITANT ORGAN DYSFUNCTION

• Cardiac: Patients have been reported to have a higher incidence of ischemic heart disease. • Neurologic: CP often manifests as a motor disorder involving spasticity and contractures. Most will have cognitive dysfunction and seizure disorders. Also seen are visual, auditory, and sensory impairments. Neurosis and psychosis can occur. • Pulmonary: Chronic lung disease is a frequent manifestation due to either chronic aspiration pneumonia, neonatal respiratory distress syndrome, bronchopulmonary dysplasia, asthma/reactive airway disease, or scoliosis causing restrictive lung disease.

• Musculoskeletal: Because of chronic immobility, patients can have marked osteopenia and may be more prone to fracture. Contractures may also make vascular access and positioning difficult under anesthesia. Patients may have TMJ disorder with poor mouth opening. • GI: May have poor nutritional status, gastroesophageal reflux disorder (GERD), drooling, and constipation. Dental caries and poor dentition are also common. • Immunologic: May be immunosuppressed due to malnutrition. • Genitourinary: Chronic urinary tract infections due to neuropathic bladder. These patients are at increased risk of latex allergy due to repeated urinary catheterizations.

CIRCUMSTANCES TO DELAY/ CONDITIONS • Acute respiratory infection/pneumonia • Acute baclofen withdrawal • Acute heart failure

CLASSIFICATIONS

Classified according to resting tone and limb involvement: • Spastic hemiplegia: Predominantly on one side of the body, with the upper extremity more involved than the leg. • Spastic diplegia: Affecting bilateral lower extremities more than upper extremities. • Spastic quadriplegia: All extremities. • Athetoid/dyskinetic CP: Associated with mixed muscle tone and extrapyramidal signs. • Ataxic CP: Caused by damage to cerebellum. Balance while walking is affected. • Hypotonic CP: Limp musculature.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Consider anxiolytic medication if appropriate • In hypotonic patients, sedative premedication is best avoided because it can decrease airway reflexes. INTRAOPERATIVE CARE Choice of Anesthesia

As the CP patient population can have significant cognitive dysfunction as well as cardiopulmonary comorbidities, general anesthesia should be considered carefully. Monitors

• Standard ASA monitors • Consider measurement of urine output

Induction/Airway Management

• Airway management can be difficult because of TMJ disorder/dislocation and poor

dentition. • Patients can have reactive airway disease. • Because of the upregulation of acetylcholine receptors in the neuromuscular junction, the patient can have decreased sensitivity to nondepolarizing neuromuscular blockers. However, due to changes in volume of distribution, there may be an increased amount of medication available at the neuromuscular junction. These changes most likely counteract each other. • Succinylcholine is considered safe to use. • In patients where GERD is a concern, consideration of a rapid sequence induction is appropriate in patients with intravenous access. However, there is no strong evidence that this is safer than a well-positioned inhalational induction, so as to minimize passive regurgitation.

Maintenance

• Keep patients warm as CP patients are prone to hypothermia due to muscle atrophy. • Minimum alveolar concentration (MAC) and drug clearance may be affected by the use of anticonvulsants.

Extubation/Emergence

• Ensure full reversal if muscle relaxation was used. • CP patients often have increased secretions so an intact cough reflex is crucial to prevent postoperative pulmonary complications. • Consider prophylaxis for postoperative nausea and vomiting.

FOLLOW-UP BED ACUITY

• Consider monitoring in a high-dependency environment for those with significant comorbidities, seizure disorder, or the potential for baclofen withdrawal if unable to take usual therapy. • Vigilance for respiratory dysfunction, hypothermia, and hypoxia • Respiratory therapy and incentive spirometry • Consider supplemental oxygen (nasal cannula, face mask) • Ensure appropriate analgesia as patients will often have difficulty in communicating.

COMPLICATIONS

• Perioperative aspiration: Treat with supportive measures including supplemental oxygen, chest physiotherapy, and ventilatory support in severe cases. • Baclofen withdrawal: Can manifest as anxiety, confusion, pain, muscle spasm, seizures, and autonomic instability. Resume baclofen regimen as soon as appropriate. • Seizure: May be precipitated by inadequate blood levels of anticonvulsant medication or electrolyte abnormality. Look for other causes of perioperative lowering of seizure threshold. Treat with benzodiazepines, supportive care, and resume previous anticonvulsant regimen as soon as appropriate.

REFERENCES

1. Krigger KW. Cerebral palsy: An overview. Am Fam Physician. 2006;73:91–102.

2. Cans C, De-la-Cruz J, Mermet M-A. Epidemiology of cerebral palsy. Paediatr Child Health. 2008;18:393–398.

3. Prosser D, Sharma N. Cerebral palsy and anaesthesia. Contin Educ Anaesth Crit Care Pain. 2010;10(3):72–76. 4. Jacobsson B, Hagberg G. Antenatal risk factors for cerebral palsy. Best Pract Res Clin Obstet Gynaecol. 2004;18(3):425–436.

ADDITIONAL READING

• www.aacpdm.org • American Academy for Cerebral Palsy and Developmental Medicine

See Also (Topic, Algorithm, Electronic Media Element) • Gastroesophageal reflux disease • Aspiration • Asthma

CODES ICD9 • 343.0 Congenital diplegia • 343.1 Congenital hemiplegia • 343.9 Infantile cerebral palsy, unspecified ICD10 • G80.0 Spastic quadriplegic cerebral palsy • G80.1 Spastic diplegic cerebral palsy • G80.9 Cerebral palsy, unspecified

CLINICAL PEARLS

• Assess the severity of disease in order to plan an appropriate anesthetic technique. • Enlist the help of the parent/guardian as they sometimes have extensive knowledge about previous surgeries and anesthetics. • Evaluate cardiopulmonary status as these patients may have extensive comorbidities including pulmonary hypertension, chronic aspiration, scoliosis, and ischemic heart disease. • Resume normal anticonvulsants and antispasmodics as soon as possible to prevent seizures and withdrawal symptoms. • Ensure patients have adequate pain control postoperatively, as they will often have difficulty communicating.

CEREBRAL VASOSPASM Victor Duval, MD

BASICS • Cerebral vasospasm is defined as the constriction of one or more major cerebral arteries, usually secondary to subarachnoid hemorrhage (SAH) or craniocerebral trauma. • The amount of blood in the basal cistern and the presence of intraventricular blood correlate with the risk of developing clinically significant cerebral vasospasm. • The diagnosis can be made clinically, angiographically, or by transcranial Doppler (TCD). • The resulting decrease in cerebral blood flow (CBF) can lead to ischemia and infarction, and is a main cause of permanent neurologic injury and death after SAH. • Up to 70% of patients with SAH demonstrate angiographic evidence of vasospasm. • Clinical symptoms of cerebral ischemia and infarction develop in 30–40% of patients.

Up to 1.2 million patients per year are estimated to have permanent or fatal neurologic injury as a result of vasospasm following an intracranial bleed. Morbidity

Vasospasm may be detectable for up to 14 days after SAH. Symptoms can range from subtle focal deficits to debilitating neurologic injury, and typically peak between 3 and 12 days. Mortality

The risk of death in patients who develop vasospasm following SAH can reach 3 times that of patients who do not. • The cause of vasospasm following SAH is still unknown. It is thought that the presence of blood in the subarachnoid space can lead to cerebral vasoconstriction. Various components and breakdown products have been proposed as mediators. Oxyhemoglobin has several properties that make it one of the most likely candidates. • The Fisher grade on initial presentation is highly predictive of the development of clinically significant cerebral vasospasm. The presence of thick blood in the basal cistern and intraventricular or intraparenchymal hemorrhage is associated with the highest risk of poor neurologic outcome. • Although patients > 68 years of age are more likely to develop symptomatic vasospasm, younger patients are more likely to show angiographic evidence of vasospasm. • Female gender, hypertension, elevated intracranial pressure (ICP), smoking, and cocaine use also increase the risk of developing vasospasm. • Contraction of smooth muscle in the vessel wall leads to lumen narrowing and restricted blood flow. Cerebrovascular resistance shifts from the penetrating arterioles to the major branches of the Circle of Willis, which undermines the brain’s ability to autoregulate. BP then becomes the main determinant of CBF beyond the affected vessels. • There is also evidence that histological changes occur. These include thickening of all three

vascular layers, periadvential inflammation, and myointimal hyperplasia. However, the extent of the clinical significance of these findings is unclear.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Since autoregulation in the brain is impaired, hypotension should be avoided throughout the perioperative period; flow is pressure dependent. • Hypertension, hypervolemia, and hemodilution (triple-H therapy) can potentially minimize the risk of ischemia; however, it is associated with a significant risk of morbidity that must be carefully weighed against this unproven benefit. Invasive monitoring is recommended. • Consider avoiding volatile agents. Uncoupling of CBF and cerebral metabolic rate of oxygen consumption (CMRO2) may lead to lower cerebral vascular resistance in unaffected areas of the brain. This can decrease perfusion distal to spastic vessels. Intravenous agents such as propofol have a more favorable profile in the setting of vasospasm.

PREOPERATIVE ASSESSMENT • Decreased level of consciousness is the most common finding indicative of cerebral vasospasm. • Rarely, patients can present with focal neurologic findings without a global decrease in level of consciousness.

Cerebral vasospasm usually occurs within 2 weeks of SAH. Patients often have comorbid conditions associated with cerebrovascular disease, such as hypertension and smoking.

Focal neurologic deficits depend on the affected vessels. Associated findings are contralateral and can involve cranial nerves, motor function, and sensory function. Brainstem function and coordination are usually intact. TREATMENT HISTORY

• Patients with cerebral vasospasm may have had an aneurysm surgically clipped or endovascularly embolized. • Triple-H therapy is widely used.

MEDICATIONS

• Most patients with symptomatic vasospasm are treated with calcium channel blockers. Nimodipine has been shown to provide some benefit. Its intravenous equivalent nicardipine, on the other hand, has demonstrated inconclusive results. • Other medications that have been experimented with include fibrinolytic therapy, sodium nitroprusside, magnesium, cyclosporine, erythropoietin, and clazosentan. • Electrolytes should be checked, especially if the patient is suspect to have developed cerebral salt wasting syndrome or SIADH. • CBC • EKG: “Canyon T-waves" are common. Nonspecific T-wave changes, QT prolongation, STsegment depression, and U waves can also occur. The EKG changes usually do not reflect the degree of myocardial dysfunction, nor do they predict the development of cardiac

failure. The EKG should be monitored for potential lethal dysrhythmias, including Torsades de Pointes, in the setting of QT prolongation, which can frequently occur in patients with severe SAH. • Elevated troponin levels are common but are usually lower than those associated with cardiac ischemia.

CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular – Cerebral vasospasm may, in and of itself, lead to hypovolemia for unknown reasons. – Reversible myocardial stunning can occur in the setting of SAH. Its severity is associated with the degree of neurologic injury. – Aneurysms occur more frequently in certain genetic conditions such as polycystic kidney disease, coarctation of the aorta, fibromuscular hyperplasia, and connective tissue disorders. • Pulmonary function should be assessed in patients who are smokers. Also, patients with compromised neurologic status are at an increased risk of aspiration. • Patients on triple-H therapy are at risk of developing cardiac, pulmonary, and renal complications.

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Delay in surgical clipping after SAH or interventional radiologic procedures to treat vasospasm can have severe consequences, including rebleeding and devastating neurologic injury. • If ischemic heart disease is suspected, an echocardiogram may be helpful in guiding intraoperative management.

CLASSIFICATIONS

• The Fisher grade classifies the appearance of SAH on CT scan and correlates it to the risk of clinically significant vasospasm: – Grade 1: No hemorrhage evident – Grade 2: SAH < 1 mm thick – Grade 3: SAH > 1 mm thick – Grade 4: SAH of any thickness with intraventricular hemorrhage or parenchymal extension.

TREATMENT Premedications

Anxiolytics are seldom necessary and can interfere with neurological exam. Special Concerns for Informed Consent

Since vasospasm can affect sensorium, informed consent may not be obtainable from the patient. It is wise to identify a surrogate decision maker in light of the significant risk of neurologic complications.

Choice of Anesthesia

General endotracheal Monitors

• Standard ASA monitors • An arterial line should always be used, and can be most helpful if placed before induction. • Central line monitoring may be useful to help guide fluid management (especially in elderly patients) or pressor support, as well as in the setting of myocardial dysfunction.

Induction/Airway Management

• Specific anesthetic agents should be selected on a case-by-case basis to fulfill the anesthetic goals described above. • Poorly organized clot in the early stages after SAH is particularly prone to rebleeding secondary to systolic hypertension and tachycardia. A rebleed during induction is often lethal. It is therefore extremely important to avoid excessive, sustained systolic hypertension and secure the airway quickly in these patients. On the other hand, prolonged hypotension should also be avoided to minimize the risk of ischemia.

Maintenance

• Inhaled agents can increase the CBF. This undermines brain relaxation and the ability to maintain a high cerebral perfusion pressure (CPP); alternatively, propofol has a more favorable profile. • Elevation of the mean arterial pressure (MAP) may be achieved with phenylephrine or dopamine. • Recent evidence suggests that hyperventilation should be avoided unless absolutely necessary to temporarily decrease ICP; vasoconstriction can further worsen ischemia. • The dose and timing of mannitol administration varies per surgeon preference. Usual doses range between 1 and 2 g/kg, and may be given immediately following induction or on initial skin incision. Surgeons may also request an additional dose at the time of dural opening.

Extubation/ Emergence

• The objective is for the patient to be able to participate in a neurological exam yet comfortable enough to minimize reaction to extubation. Using a relatively low dose of fentanyl 15–20 minutes before extubation can be highly effective; alternatively a remifentanil infusion may be considered. Intravenous lidocaine can also be used to suppress the coughing reflex. • Hypertension and tachycardia on emergence is common and is usually not related to painful stimuli. This is usually best treated with beta-blockers. • Prophylaxis against postoperative nausea and vomitting should be given to decrease the risk of postoperative bleeding secondary to the sudden and severe rise in ICP associated with vomiting.

FOLLOW-UP

BED ACUITY

Patients at high risk for vasospasm, based on clinical and radiologic findings post-SAH, should be monitored at least every 2 hours for neurologic changes. This is usually done in an intensive care unit (ICU) setting. Lower risk patients can be monitored every 4 hours. MEDICATIONS/LAB STUDIES/ CONSULTS

• Patients at risk for cerebral vasospasm are almost always placed on a nicardipine drip. They may further be placed on a pressor such as norepinephrine to maintain MAPs that are 10– 20% above baseline. • Daily labs should include CBC, chemistry panel, and measures of urine function. • TCD can be a useful screening tool but is fraught with technical limitations. Magnetic resonance angiography (MRA) is more reliable. Cerebral angiography is the gold standard for diagnosis. • Consults should be obtained as clinically indicated if cardiac, pulmonary, or renal complications are detected. • One should be prepared for the risk of significant bleeding intraoperatively. This can lead to malignant brain swelling with devastating consequences. Brain protection and brain relaxation techniques should be immediately instituted in such an event. • As with any neurosurgical procedure, there is risk of intracranial hemorrhage. Patients should be monitored closely for changes in neurological function for at least 24 hours postoperatively. • There is also the potential for developing an intraoperative infarct, especially if hypotension is maintained. This may present in the postoperative period as delayed emergence, altered mental status, or focal neurologic deficits. • Any of the above complications resulting in neurologic injury can lead to compromised airway reflexes, which puts the patient at risk for aspiration. • Triple-H therapy can lead to additional complications, such as cerebral edema, cardiac ischemia, pulmonary edema, and hyponatremia. Patients should be closely monitored in an ICU. Central venous pressure monitoring is recommended.

REFERENCES

1. Alaraj A, Charbel FT, Amin-Hanjani S. Peri-operative measures for treatment and prevention of cerebral vasospasm following subarachnoid hemorrhage. Neurol Res. 2009;31(6):651–659. 2. Lee KH, Lukovits T, Friedman JA. “Triple-H” therapy for cerebral vasospasm following subarachnoid hemorrhage. Neurocrit Care. 2006;4:68–76. • Craniotomy, cerebral aneurysm clipping • Cerebral embolization • Cerebral blood flow

CODES

ICD9

435.9 Unspecified transient cerebral ischemia ICD10

G45.9 Transient cerebral ischemic attack, unspecified

CLINICAL PEARLS

• The extent of SAH and the patient’s subsequent neurologic status can predict the likelihood of developing cerebral vasospasm. • A change in the level of consciousness after SAH or postaneurysm clipping should always be investigated for the possibility of vasospasm in the first 2 weeks. • It is important to avoid prolonged periods of hypotension in order to minimize the risk of ischemia. • The benefit of triple-H therapy has yet to be proven; additionally, it can lead to significant complications, especially if the patient is not monitored closely.

CEREBROSPINAL FLUID Brooke Albright, MD, MAJ, MC

BASICS DESCRIPTION

Cerebrospinal fluid (CSF) is a clear, colorless fluid surrounding the central nervous system (CNS) that provides physical protection and a chemically stable environment. PHYSIOLOGY PRINCIPLES

• CSF is a direct extension of the extracellular fluid compartment of the CNS. – The volume of CSF in an adult is ∼150 mL and in infants 50 mL. – It is secreted and absorbed continuously throughout the day, with daily production in adults ∼500–600 mL. – Absorption is pressure dependent and linear over a wide range. • CSF provides nourishment to the brain as well as assists in removing by-products of neuronal metabolism. • Electrolyte composition – Differs from that of plasma due to the blood–CSF barrier, which allows free diffusion of water, gases, and lipid-soluble compounds but requires active or passive transport of glucose, amino acids, and ions. – CSF is composed primarily of sodium, chloride, and bicarbonate. – Proteins are largely excluded from CSF. See Table 1 for comparison of CSF to plasma (1). Table 1 Composition of CSF: Plasma

• A decrease in plasma pH results in a similar decrease in CSF pH due to the ability of carbon dioxide to easily cross the blood–brain barrier.

ANATOMY

• Site of production. Ninety percent of CSF is formed from blood in the choroid plexus of the lateral, 3rd, and 4th ventricles. The remaining 10% is formed from brain substance. • Nutrients reach neurons and glial cells either by – Crossing the blood–CSF barrier that is regulated by the choroid plexus or, – Crossing the blood–brain barrier of cerebral capillaries. • The blood–CSF barrier is formed by impermeable “tight junctions” between epithelial cells that regulate the diffusion of certain molecules. • Once molecules enter the CSF, they travel to the interstitial fluid surrounding neurons and glial cells by diffusing through a “leaky” ependymal layer. • Arachnoid villi (granulations) in the superior sagittal, transverse, and other venous sinuses absorb the majority of CSF. The rest is absorbed by veins in the cranial and spinal subarachnoid spaces and lymphatic vessels of the cranial and spinal nerves.

DISEASE/PATHOPHYSIOLOGY

• Normal intracranial pressure (ICP) is usually 5–15 mm Hg and is comprised of – Intracranial CSF – Brain tissue – Intracranial blood (arterial and venous) • Compensation. An increase in any one component of intracranial volume must be offset by a decrease in another component to prevent an increase in ICP. Initially, as the intracranial volume increases, CSF is shifted from the cranium to the spinal subarachnoid space, in order to prevent an increase in ICP. • Increased ICP. If the intracranial volume continues to increase beyond the ability of the CSF to translocate, then an exponential rise in ICP is likely with associated clinical symptoms. • Nonobstructive hydrocephalus is a condition of increased production or decreased absorption of CSF. Obstructive or noncommunicating hydrocephalus occurs when there is a blockage anywhere along the path of CSF flow (e.g., tumor, congenital structural abnormalities, infection, and trauma). Treatment depends on the etiology of the hydrocephalus. In certain situations, the placement of a CSF shunt is indicated in order to translocate CSF and lower the ICP, thereby maintaining cerebral perfusion (CPP = MAP − ICP, where CPP is cerebral perfusion pressure, MAP is mean arterial pressure). • CSF leak. Leakage of CSF into the nasal, oral, ear, or dermal sinus cavities can result from trauma, intracranial surgical procedures, infection, hydrocephalus, congenital malformations, or neoplasms. Interruption of the anterior cranial fossa floor allows leaks of CSF through the cribriform plate. It most commonly presents as otorrhea or rhinorrhea and is exacerbated by a Valsalva-type maneuver (coughing, sneezing, bending, heavy lifting, and straining). • Postdural puncture headache (PDPH) occurs most frequently after a “wet tap” and is a phenomenon related to the spontaneous loss of CSF from the subarachnoid to the epidural space. – Most common complication of neuraxial anesthesia due to a knick in the dura from a relatively large sized needle. – Manifests as pain or stiffness in the neck, nausea or emesis, diplopia due to unilateral or bilateral sixth nerve palsy, dizziness, changes in hearing, visual blurring, photophobia, intrascapular pain, facial numbness or weakness, galactorrhea, and/or radicular upper limb symptoms. – Debate exists over the timing and use of epidural blood patches in the treatment of PDPHs. Current literature does not support prophylactic epidural blood patches over other treatments because there are too few trial participants to allow reliable conclusions to be drawn. However, therapeutic epidural blood patch showed a benefit over conservative treatment based on available evidence (2)[A].

PERIOPERATIVE RELEVANCE

• Neuraxial anesthesia involves the injection of local anesthetics and/or narcotics either into the intrathecal space where CSF bathes the spinal cord (spinal anesthesia) or into the epidural space where the nerves exit the spinal cord through the dura. Neuraxial anesthesia is used primarily in surgeries involving the lower extremities, abdomen, and/or pelvis. Potential benefits of neuraxial techniques include reduced blood loss, blood clots, incisional pain with respiration, atelectasis, pneumonia, and need for narcotics; as well as a quicker

return of bowel function, ambulation, and patient satisfaction (3)[A]. For Cesarean section, it is considered advantageous over a general anesthetic in regard to the simplicity of the technique, reduced risk of systemic toxicity to mother and fetus, and maternal satisfaction. There is no difference between epidural and spinal anesthesia shown with respect to failure rate, need for additional intraoperative analgesia, conversion to general anesthesia intraoperatively, maternal satisfaction, and neonatal intervention (4)[A]. • Neuraxial local anesthetics used for spinal anesthesia are characterized according to their baricity (e.g., hypobaric, isobaric, or hyperbaric), which is the ratio of the density of the solution at a specified temperature compared to the density of CSF (1.0001–1.0005 at 37°C) (5). – Hypobaric solutions (density <0.9998) “float" upward. – Hyperbaric solutions (density >1.0008) “sink" downward. – Isobaric solutions (density between 0.9998 and 1.0008) “stay" at the point of injection. • Neuraxial opioids work on opioid receptors (primarily mu receptors) in the substantia gelatinosa of the spinal cord. – Analgesia is better for visceral rather than somatic pain. – An advantage of neuraxial opioids compared to local anesthetics is that analgesia is produced without sympathetic nervous system denervation, skeletal muscle weakness, or loss of proprioception. – Onset of analgesia, duration of action, and cephalad movement in the intrathecal space depend on lipid solubility. Poorly lipid-soluble opioids, such as morphine, have a slower onset, longer duration of action, and remain in the CSF longer for transfer to more cephalad locations than highly lipid-soluble opioids, such as fentanyl. – Coughing or straining can also affect opioid movement in the CSF. However, body position does not usually affect opioid movement. – Vascular absorption after intrathecal administration of opioids is minimal; however increased with lipid-soluble drugs. – Side effects of neuraxial opioids are dose dependent and include pruritus, nausea and vomiting, urinary retention, and respiratory depression. – Cephalad migration of morphine in the CSF can lead to respiratory depression 6–12 hours after neuraxial administration due to an interaction with opioid receptors in the ventral medulla. • “Wet tap.” Accidental dural puncture is possible during epidural anesthesia. It is recognized by the appearance of warm CSF (versus cold saline used to identify loss of resistance) at the hub of the epidural needle during placement. When this happens, a postdural puncture headache is likely due to the large hole created in the dura by the epidural needle, allowing the leakage of CSF from the intrathecal space to the epidural space. • Ventriculostomy: Aseptic placement of a pressure transducer into the subdural space (subdural bolt), brain parenchyma, or ventricle that allows ICP monitoring as well as the withdrawal of CSF. One major benefit of such a drainage system is that it can be organized to only drain CSF when the ICP rises above a selected value. Another benefit is that CSF can be easily obtained for lab analysis. • Lumbar subarachnoid catheter (lumbar drain): CSF can be withdrawn or allowed to passively drain.

– Utilized in thoracoabdominal aortic aneurysm surgery at some institutions. Purpose is to reduce the CSF pressure, improve blood flow to the spinal cord, and reduce the risk of ischemic spinal cord injury. However, current available evidence does not fully establish CSF drainage as a method of protection (6)[A]. – Lumbar CSF pressure may not accurately reflect ICP secondary to compartmentalization. – There is a risk of tonsillar herniation with the drainage of CSF via lumbar subarachnoid catheters in certain patients (i.e., brain tumor). • Decreased pH in the CSF. Occurs with respiratory acidosis and stimulates ventilation via the medullary chemoreceptors located in the fourth cerebral ventricle. Over time, the pH is restored to normal by the active transport of bicarbonate ions into the CSF. Conversely, in respiratory alkalosis, bicarbonate ions are actively transported out of the CSF (7).

REFERENCES

1. Modified from Table 27-2, Anesthesia for Neurosurgery. In Barash PG, Cullen BF, Stoelting RK (Eds.), Clinical Anesthesia, 5th ed., p. 750. Philadelphia, Lippincott Williams and Wilkins, 2006. As adapted with permission from Artru AA: Cerebrospinal Fluid. In Cottrell JE, Smith DS (Eds), Anesthesia and Neurosurgery, p. 95. St Louis, CV Mosby, 1994. 2. oonmak P, Boonmak S. Epidural blood patching for preventing and treating post-dural puncture headache. Cochrane Database Syst Rev. 2010;1:CD001791. 3. arbosa FT, Cavalcante JC, Jucá MJ, et al. Neuraxial anaesthesia for lower-limb revascularization. Cochrane Database Syst Rev. 2010;1:CD007083. 4. g KW, Parsons J, Cyna AM, et al. Spinal versus epidural anaesthesia for caesarean section. Cochrane Database Syst Rev. 2004;2:CD003765. 5. rnst A. In vitro changes of osmolality and density of spinal anesthetic solutions. Anesthesiology. 1968;29:104. 6. itchell RA, Singer MM. Respiration and cerebrospinal fluid pH in metabolic acidosis. J Appl Physiol. 1965;20:905–911. 7. Khan SN, Stansby GP. Cerebrospinal fluid drainage for thoracic and thoracoabdominal aortic aneurysm surgery. Cochrane Database Syst Rev. 2004;1:CD003635.

ADDITIONAL READING

• Covino BG, Scott DB, Lambert DH. Cerebral Spinal Fluid. Handbook of Spinal Anaesthesia and Analgesia. WB Saunders Company. 1994:46–47. • Barash PG, Cullen BF, Stoelting RK (Eds.). Anesthesia for neurosurgery. In: Clinical Anesthesia, 5th ed. Lippincott Williams and Wilkins. 2006: 749–750.

See Also (Topic, Algorithm, Electronic Media Element) • Epidural • Ventriculo-peritoneal shunt • Intracranial hypertension

CLINICAL PEARLS

• PDPH is the most common complication of neuraxial anesthesia and is related to the loss of CSF from intrathecal to epidural space. • CSF is a component of ICP and can be drained in certain situations to decrease ICP and help improve CPP temporarily.

CERVICAL PLEXUS BLOCK Maged N. Guirguis, MD Sherif Zaky, MD, PhD

BASICS DESCRIPTION

• Deep and superficial cervical plexus blocks can provide anesthesia to the neck and upper shoulders. – Superficial cervical plexus block can be used alone for many superficial neck surgeries or in conjunction with a deep cervical block for more invasive procedures, including thyroidectomy or carotid endarterectomy (CEA). – If a superficial cervical plexus is used alone, local anesthetic supplementation from the surgeon might be required for deeper structures. • Postoperative analgesia; can last up to 8 hours after the time of the block, depending on the local anesthetic chosen. • Indications – CEA; allows for an awake patient and continuous neurological assessment. – Thyroid operations; when general anesthesia poses high risk, especially in patients with significant cardiac history. – Superficial neck surgeries; such as lymph node dissection and excision of thyroglossal or branchial cysts. • Contraindications – Absolute: Patient refusal – Relative Infection at the site of injection Sepsis Coagulopathy Preexisting central or peripheral nervous system disorders Allergy to local anesthetics • Advanced pulmonary disease. Deep cervical blocks will also result in blockade of C3, C4, and C5 (diaphragmatic innervation); this may result in pulmonary embarrassment. Alternatively, a superficial cervical plexus block with local anesthetic supplementation from the surgeon should be considered. PHYSIOLOGY PRINCIPLES

• Cutaneous innervations to the head and neck. Innervation by the trigeminal and cervical nerves can be delineated by a straight line from the vertex of the head to the ear to the chin (e.g., the “vertex-ear-chin line”). The trigeminal nerve provides sensory innervations above this line, whereas the upper cervical nerves provide sensory innervations below. The cervical plexus is formed from the ventral rami of the upper four cervical nerves (C1–C4). It supplies sensation to the neck, upper shoulders, and chest, as well as motor branches to the

diaphragm and some neck muscles. – The cervical plexus lies on the anterior surface of the levator ani scapulae and scalenus medius muscles, covered by the sternocleidomastoid muscle. The plexus at this plane gives origin to both superficial and deep branches. Superficial branches (superficial cervical plexus) give rise to cutaneous nerves of the skin and superficial structures of the head, neck, and shoulders. – Deep branches (deep cervical plexus) give rise to motor and communicating branches of the anterior neck muscles and diaphragm (C3, C4, components). • Superficial cervical block. A technique that blocks the superficial branches of the cervical plexus nerves at the posterior border of the sternocleidomastoid. In high-risk patients (e.g., significant pulmonary disease), superficial cervical plexus block alone can be used with local anesthetic supplementation by the surgeon. • Deep cervical block. A technique that blocks the nerves at the paravertebral level near the vertebral foramina. This blocks C2–C4 prior to forming the plexus.

ANATOMY

• Cervical plexus. The dorsal and ventral roots of C2, C3, and C4 combine to form spinal nerves after exiting their respective foramina. They subsequently form ascending and descending branches that come together to form the cervical plexus. The cervical plexus divides into superficial and deep cervical branches that emerge from the posterior triangle, midway on the posterior border of the sternocleidomastoid. • Superficial or cutaneous branches – Lesser occipital nerve (ascending branch) is a direct branch of C2. – Greater auricular (ascending) nerve arises from C2 and C3. – Transverse cervical nerve arises from C2 and C3. – Supraclavicular nerves (descending) are three nerves that receive innervations from C3 and C4. They innervate regions of the suprascapularis, shoulder, and upper thoracic region. • Deep branches – C1 is mostly a motor nerve that is not blocked by superficial or deep techniques. – C2 provides a branch to the sternocleidomastoid. – C3 and C4 may send a sensory branch to the spinal accessory nerve or deep surface of the trapezius. • Nerve branches from C2 to C4 that branch out prior to the cervical plexus. – C3, C4 contribute to the phrenic motor nerve. – C4 can also send a branch caudally and join C5, thus functioning as part of the brachial plexus. • Landmarks – Mastoid process – Transverse process of the sixth cervical vertebra (Chassaignac’s tubercle) – Posterior border of the sternocleidomastoid muscle

PHYSIOLOGY/PATHOPHYSIOLOGY

• Phrenic nerve blocks can lead to respiratory distress in patients with underlying pulmonary disease. In healthy patients, unilateral phrenic nerve block is usually asymptomatic due to

respiratory reserve and an intact contralateral phrenic nerve. • Underlying bleeding disorder or patients taking anticoagulants. Bleeding in this area is problematic; hematoma may occur if the needle enters a large blood vessel and might compromise the airway. • There are case reports of deterioration or worsening of pre-existing neurological disorders, such as diabetic neuropathy or multiple sclerosis. • Local anesthetic systemic toxicity. The vertebral artery directly supplies the brain; it is also in close proximity to the site of injection and very small amounts of intravascular injection can result in CNS effects. • Inadvertent subarachnoid or epidural anesthesia can result due to the proximity to the spinal foramina. It can lead to total spinal anesthesia and respiratory arrest. • Infection is possible, but very low risk.

PERIOPERATIVE RELEVANCE

• Deep cervical block – Position. The patient should be positioned supine with the neck slightly extended and the head rotated away from the side of the block. – Landmarks to identify the location of C2–C4 as they emerge from the foramina. A line connecting the mastoid process and the transverse process of C6 is drawn, while the nondominant hand palpates behind the posterior border of the sternocleidomastoid muscle. Label C2, C3, and C4 levels 2, 4, and 6 cm, respectively, from the line starting caudal to the mastoid process. – Prep Supplemental oxygen is usually applied with a nasal cannula, facemask, or blow-by while avoiding straps in the sterile field. The skin is cleaned and prepped in usual sterile fashion Subcutaneous infiltration of local anesthetic is administered along the line over the transverse processes; this allows the anaesthetist to move the needle caudally and cephaladly to block each level. – Needle insertion A 1 ½ inch, 22 gauge, short-beveled needle (connected to a 20 cc syringe of local anesthetic, typically with extension tubing) is inserted between palpating fingers and advanced perpendicular to the skin plane with a slightly caudal angulation. Advance slowly until the transverse process is contacted, typically at a depth of 2–3 cm. Withdraw the needle 1–2 mm. Aspirate to rule out blood or cerebrospinal fluid. Local anesthetic (3–5 mL) is slowly injected with frequent intermittent aspiration. Remove the needle and repeat the block at the next level. Alternatively, some practitioners inject 15 mL at the C3 level only to avoid repeated passes (3). • Superficial cervical plexus block – Landmarks. A line connecting the mastoid process to the C6 transverse process is drawn. – Prep. As above; usual sterile prep. Subcutaneous infiltration should occur at the midpoint of the line.

– Needle insertion A 1 ½ inch, 25 gauge, short-beveled needle (connected to 20 cc syringe of local anesthetic, typically with extension tubing) is introduced through the numbed area and passed inferiorly and superiorly along the posterior border of the sternocleidomastoid. A total of 10–15 mL of local anesthetic should be injected in both directions. • Local anesthetic (3). The potential toxicity of a particular drug and concentration must be weighed against the benefits of using that drug. The length of the surgery must also be taken into account, as different local anesthetics have different durations of action. The following have been used and described in the literature: – 1.5% Mepivacaine – 2% Lidocaine – 0.5% Ropivacaine – 0.25% Bupivacaine • Ultrasound guided deep cervical plexus block: Multiple techniques have been described. One easy approach involves a single injection of local anesthetic under the carotid artery using 15–20 ml of local anesthetic to block the roots of the cervical plexus. This is usually done using a high frequency ultrasound probe to obtain a short axis (cross section) view of the carotid artery while the needle is inserted in plane with the probe from its lateral end. Local anesthetic will be injected deep to the carotid artery at around the C6 transverse process. • Signs of a successful block. Sensory block within cutaneous segments of the lesser occipital, greater auricular, transverse cervical, and supraclavicular nerves, as well as relaxation of the ipsilateral neck muscles. Ipsilateral ptosis, hyperemic conjunctiva with warm sensation of the face, and nasal obstruction are also common due to associated block of the sympathetic fibers. • CEA (1,2) – Pros: Allows for an awake neurological exam and avoids hemodynamic shifts. Shunts are less commonly utilized. – Cons: Patient interference, lack of anesthetic medications with neuroprotective qualities, and the need to secure the airway in the event of stroke, hemorrhage, seizure, agitation, or hypoxia. – Cervical plexus blockade for CEA also can be effectively performed with a single injection at C3 level. However, studies have not shown significant difference in quality of anesthesia during surgery compared to the classic method described above. • Combined deep and superficial cervical blocks are usually done together for neck surgeries. • Combined versus superficial plexus blocks for minimally invasive neck surgeries (e.g., parathyroidectomy). Some studies suggest that there is no difference in onset of block or pain scores (4).

GRAPHS/FIGURES

REFERENCES

1. Fiorani P, Sbarigia E, Speziale F, et al. General anaesthesia versus cervical block and perioperative complications in carotid artery surgery. Eur J Vasc Endovasc Surg. 1997;13:37–42. 2. Merle JC, Mazoit JX, Desgranges P, et al. A comparison of two techniques for cervical plexus blockade: Evaluation of efficacy and systemic toxicity. Anesth Analg. 1999;89:1366–1370. 3. Gratz I, Deal E, Larijani GE, et al. The number of injections does not influence absorption of bupivacaine after cervical plexus block for carotid endarterectomy. J Clin Anesth. 2005;17(4):263–266. 4. Pintaric TS. A prospective, randomized comparison between combined (deep and superficial) and superficial cervical plexus block with levobupivacaine for minimally invasive parathyroidectomy. Anesth Analg. 2007;105(4):1160–1163. 5. Usui Y, Kobayashi T, Kakinuma H, et al. An anatomical basis for blocking of the deep cervical plexus and cervical sympathetic tract using an ultrasound-guided technique. Anesth Analg. 2010;110:964–968. www.nysora.org See Also (Topic, Algorithm, Electronic Media Element) • Local anesthetic systemic toxicity

• Parathyroidectomy • Carotid endarterectomy • Thyroidectomy • Total spinal

CLINICAL PEARLS

• Branching of spinal nerves. C2–C4 spinal cord→ dorsal and ventral root (before exiting foramina)→ spinal nerves (after exiting foramina)→ ascending and descending branches → CERVICAL PLEXUS → superficial and deep cervical branches →individual nerves or contributions to other nerves.

CHEST TUBES

Marc A. Logarta, MD, DABA, FANZCA

BASICS DESCRIPTION

• Tube thoracostomy is performed to drain collections of fluid or air in the pleural space. If the collection is compressing the lung, removal can result in re-expansion and improved V/Q matching. If the air collection is under pressure (e.g., tension pneumothorax), removal can be life saving. • Tube thoracostomy was initially introduced in the early 1870s; however, there is evidence that Hippocrates (circa 400 BC) initially considered drainage of the pleural compartment. • The pleural space is a potential space between the parietal pleura on the inside of the chest wall and the visceral pleura that lines the outside of the lungs (pleura are thin layers of tissue). The space contains a small amount of serous fluid to “lubricate” movement. • The pleural space’s negative pressure bestows function. Because parietal pleura adheres to the inside of the stiff chest wall space, the negative pressure in the pleural space serves to “draw" or “pull" the visceral pleura (along with the adherent lung tissue) outward. This prevents lung collapse. • Fluid and air collections in the pleural space are pathologic; they prevent adequate lung expansion (ventilation/perfusion mismatch) and create tension (positive pressure capable of shifting the mediastinum). PHYSIOLOGY PRINCIPLES

• The chest tube (a.k.a. tube thoracostomy), provides a conduit for the removal of air and fluid collections from the pleural space. By attaching to a drainage system (typically comprised of 3 chamber compartments), “one-way" flow out of the pleural space can be established. • The system works by combining the following physiologic principles: positive pressure within the thoracic cavity facilitates extrusion of air and fluid; gravity facilitates drainage of fluid; air rises in a fluid column; suction facilitates flow of air and fluid out of the pleural cavity. • Positive pressure. During spontaneous ventilation (SV), thoracic cavity pressure is positive on exhalation and negative during inhalation (downward movement of diaphragm and outward expansion of rib cage). Therefore, air and fluid are extruded out of the pleural cavity when the patient exhales. During positive pressure ventilation, thoracic cavity pressure is positive during inhalation, but negative/reduced during exhalation. Therefore, air and fluid are extruded out of the pleural cavity during inhalation. • Chest tubes. Clear plastic of varying internal diameter (8F, 12F, 16F, 20F, 24F, 28F, 32F, 36F) that is inserted into the patient’s pleural cavity and connects to the drainage system. The portion within the pleural cavity contains multiple orifices that improve drainage. Smaller diameter tubes may be placed via the Seldinger technique; however, they are more

prone to clotting from blood or fluid and therefore may be more appropriate for air collections. Additionally, a radiopaque line facilitates visualization on chest radiography. • Drainage system (collection chamber, water seal chamber, suction control chamber) – Collection chamber. Connects to the chest tube; air and fluid empty directly into this chamber via gravity, suction, and positive pressure within the chest wall. The chambers are calibrated, allowing for fluid measurement. Fluid remains here and does not enter the other chambers, or flow back into the pleural space as long as the gravitational gradient is maintained. Because air rises in a fluid column, the chambers are set up such that air enters at the bottom of a fluid-filled chamber and can only move upward (creates one-way flow). – Water seal chamber. Middle chamber; partially filled with water. Air from the collection chamber enters the bottom of this chamber and bubbles upward. Reentry of air cannot occur (air cannot move down a fluid column) and one-way flow is established. This is critical, because air would otherwise be able to reenter the pleural cavity. Air leak: Describes bubbling in the water seal chamber which indicates that air is present in the pleural space. Air leak meter: Allows for a qualitative measurement of the air leak (not quantitative; increased or decreased) Calibrated manometer: Allows measurement of the negative pressure in the pleural cavity. As intrapleural pressures become negative, the water level rises. Once negative pleural pressures are re-established, “Tidaling” occurs. Tidaling describes the rising and falling water level that corresponds with negative and positive pressures in the pleural cavity, respectively (SV: Rises with inhalation, falls with exhalation). High negativity float valve and relief chamber: Safety features that safeguard ill-effects of high negative pressures that may occur with coughing, chest tube stripping, or disconnected suction. – Suction control chamber. The most distal chamber and connects the suction source to the water seal chamber. Serves to control the level of suction, thereby protecting the pleural cavity from excessive negative pressures. Water in this chamber serves as a barrier or buffer between the suction source and patient (allows for a more “gentle” suction and helps safeguard against the ill-effects of accidental excessive suction). Thus, the height of water in this chamber determines the amount of suction transmitted to the pleural cavity.

ANATOMY

• Placement occurs with the patient supine, with the head slightly raised (30°). Expose the axilla by raising and abducting the arm, or placing the hand behind the head. • Chest tube insertion point is performed between the 3rd and 5th intercostals space at the midaxillary line. • A scalpel is used to make a superficial incision that follows the orientation of the ribs, followed by blunt dissection through subcutaneous tissue with a curved hemostat. Following identification of the parietal pleura (adheres to the inside of the ribs), the pleural tissue is punctured to enter the pleural space (rush of air or fluid occurs). The tract is dilated with the proceduralist’s finger and adhesions are swept away. The chest tube is introduced with a hemostat in the direction of the air or fluid collection to a distance sufficient for all drainage holes to be within the chest. Once in situ, the chest tube is secured at the skin with a

mattress suture, occlusively dressed, and connected in a sterile fashion to a drainage system. When smaller chest tubes are placed, a Seldinger technique may be used to guide the chest tube. • Correct positioning is often confirmed with a chest radiograph following chest tube placement. • Relative contraindications (or concerns) to chest tube placement include bleeding diatheses, infection over the chest tube insertion site, pulmonary bullae, or lung densely adherent to the chest wall throughout the hemithorax. • Placement of a chest tube has a complication rate ranging from 3% to 16% and includes improper placement resulting in an inability to drain the desired air/fluid collection; diaphragm, pulmonary, splenic, hepatic, or gastric laceration; intercostal artery bleeding; unilateral pulmonary edema following rapid removal of a large pleural effusion or pneumothorax; thoracic empyema; and persistent air leak.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Indications for the placement of a chest tube include pneumothorax, hemothorax, chylothorax, empyema, and pleural effusions. • Pneumothorax. Air collections can occur from a breach in the pleural tissue, either parietal or visceral. Causes include trauma, thoracic cavity surgery, pulmonary disease (chronic obstructive pulmonary disease [COPD], blebs/bullae, adult respiratory distress syndrome [ARDS], Marfan’s syndrome, multiorgan dysfunction), complications of central line or peripheral nerve block placement, and bronchopleural fistulas. The effects can range from subclinical (where a small portion of the visceral pleura becomes detached from the parietal wall), to life-threatening (tension pneumothorax). • Fluid collections can result from breaches in the pleural tissue or oncotic/osmotic pressure pathology. Causes include hemothorax (from surgical or traumatic injury), chylothorax (lymphatic blockade), and empyema, and pleural effusions (CHF, malignancy, cirrhosis, nephritic syndrome, lupus). The effects are due to impairment of lung expansion and vary depending on size and time of accumulation. Unless a breach in the pleural tissue occurs, they do not necessarily interfere with the negative pressure within the pleural space (thus, do not necessarily result in complete lung collapse or life-threatening tension scenarios). • Pulsus paradoxus is an exaggeration of the normal variation of systolic BP during the inspiratory phase of respiration. Normally, during inhalation the systolic BP will fall <10 mm Hg. In certain disease states where there is an increased intrathoracic pressure, the systolic pressure will fall >10 mm Hg. These disease states include pneumo/hemothorax, pleural effusion, hemomediastinum, and COPD.

PERIOPERATIVE RELEVANCE

• Management practices regarding criteria and method of removal as well as monitoring with chest radiography are variable and depend on the clinician and institution. • Intensive care unit (ICU) management: Management is centered on daily evaluation concerning the need to keep the chest tube in situ. Clinical picture, hemodynamic stability, pleural output, continued bleeding, bronchopleural fistula, and appearance on chest radiographs are factors that help management – An air leak can occur if there is a leak in the tubing or if the openings along the lumen of

the tube are outside of the chest wall. It can also occur if there is a bronchopleural fistula – one of the most feared complications of chest tube placement. – Volume of chest tube drainage. Studies suggest <2 mL/kg/day or <200 mL/day (whichever is less) may be appropriate for chest tube removal. – Removal may be done at end-inspiration or end-expiration. Studies have not shown a difference in the recurrence of pneumothorax. – After resolution of air leak/drainage, removal on water seal may result in increased recurrence, hospital stay, and number of chest radiographs ordered (compared to placing the patient on suction for 24 hours, and then removing). – Tube stripping. Conducted by some to prevent clotting (which can create a tension situation in the chest), however, has the potential to create large negative pressures or tissue injury to the lung. – Chest radiography after removal is often performed; however, studies also demonstrate that clinical exam and judgment may be sufficient. – Daily chest radiographs may not be indicated • Management outside of ICU – Water seal chamber evaluation prior to the procedure is crucial to intraoperative management. Look to see if there are bubbles – their presence indicates an air leak. If the bubbles coincide in time to the respiratory cycle, there may also be a bronchopleural fistula. – Look for tidaling during the respiratory cycle, this respiratory swing indicates a patent system. – A bubbling chest tube should not be clamped. This can lead to accumulation of air and formation of a tension pneumothorax. – Unless there are extenuating clinical circumstances, keep the drainage system upright and below the patient so as to allow drainage of any fluid to gravity. Keep on water seal so as to prevent flow of air into the pleural space. – Only attach to suction if there may be an accumulation of fluid/air in the pleural cavity. – Be prepared to deal with malfunction and even dislodgement of the chest tube. This may necessitate replacement of the chest tube on an emergent basis.

GRAPHS/FIGURES

REFERENCES

1. Miller KS, Sahn SA. Chest tubes. Indications, technique, management and complications. Chest. 1987;91:258–264. 2. Laws D, Neville E, Duffy J. BTS guidelines for the insertion of a chest drain. Thorax. 2003;58:ii53–ii59.

3. Paramasivam E, Bodenham A. Air leaks, pneumothorax, and chest drains. Conti Educ Anaesth Criti Care Pain. 2008;8(6):204–209.

ADDITIONAL READING

• www.surgicalcriticalcare.net/guidelines/chest_tube_2009.pdf See Also (Topic, Algorithm, Electronic Media Element) • Pneumothorax • Central line

CLINICAL PEARLS

• Anaesthetists may need to manage chest tubes perioperatively or in ICU patients. Additionally, pneumothorax or hemothorax that may occur with regional nerve blocks or central line placement may require the emergent placement following needle thoracostomy. • The anesthesia team should understand the pathophysiology, management strategies, and goals of chest tube drainage for patients who present to the operating room with chest tubes. Any questions or concerns should be discussed with the primary team.

CHEST X-RAY

Michael P. Hofkamp, MD James M. Callas, MD

BASICS DESCRIPTION

• A radiological study that visualizes thoracic structures in a two-dimensional plane. • Chest x-ray (CXR) is utilized in the preoperative period for examination of cardiopulmonary processes, detection of pacemakers, and confirmation of lines and tubes. In the intraoperative period, CXR is used for evaluation of acute pulmonary changes, confirmation of new line and tube placement, and possibly for evaluation of retained surgical instruments. In the postoperative period, CXR is used for confirmation of tube and line placement and evaluation of interval cardiopulmonary changes. • Intensivists routinely utilize the CXR for monitoring interval pulmonary changes and checking line and tube placement in critically ill patients. PHYSIOLOGY PRINCIPLES

• Anatomic structures can be visualized by the differential penetration of ionizing radiation. – Inverse relationship between density of anatomic structures and penetration of ionizing radiation. – High-density structures such as bone and fatty tissue attenuate the x-ray beam, and appear white on film. – Low-density structures such as air appear black on CXR. • The orientation of the ionizing radiation can affect the quality of the study. – Posterior to anterior (PA) orientation of radiation beams can produce a higher quality study but needs patient cooperation. – Anterior to posterior (AP) orientation of radiation beams distort anterior thoracic structures because these structures are further away from the x-ray plate that captures the image. The heart and pulmonary vessels appear larger on an AP view than its PA counterpart due to this difference. However, this study can be used more easily on patients who are otherwise immobile (patients in intensive care unit or operating room) or uncooperative. – Lateral films are typically performed in the upright position but can be performed supine. Lateral decubitus films can help the physician determine if there is layering of pleural fluid versus a loculated effusion. ANATOMY

• Technical considerations when ordering and examining CXR – Markings distinguishing between right and left are always placed by the technologist. – Incomplete inspiration may be misleading; decreased lung volumes give the illusion of other anatomic structures appearing larger.

– Technique of film must be taken into account. The technologist uses various settings to determine energy and timing of radiation dose and this can affect the appearance of density/contrast on the CXR. It is possible to have two completely different appearing CXRs on the same patient by simply modifying the radiological technique. • Cardiovascular – Relevant anatomy: Heart, superior vena cava (SVC), inferior vena cava, pulmonary arteries, pulmonary veins, ascending aorta, descending aorta. – Inspect the contour of the heart; it should have curves corresponding to the aorta, atrium, and ventricles. A heart devoid of these normal curves is suggestive of pericardial fluid. – The aorta should be visualized from the 12 o’clock to the 6 o’clock position as it goes from the left ventricle through the aortic arch and down to the descending aorta. – The SVC is a vague stripe along the left paratracheum that can be accentuated by the supine position. – The aortic knob and apex should be on the left. A right sided aortic knob is suggestive of situs inversus. – Heart size should take up 1/3rd or less of the chest cavity. • Pulmonary – Relevant anatomy: Trachea, mainstem bronchi, visceral pleura, diaphragm, costophrenic angle. – Trachea should be at the midline; assure that the right and left mainstem bronchi are symmetric (neither elevated nor depressed). – Lung markings should extend out to the periphery to rule out pneumothorax. – Pulmonary arteries should be symmetric. Large pulmonary arteries that rapidly taper are suggestive of pulmonary hypertension. – The density of both lungs should be the same. Air trapping, mucous plugging, and pneumothorax can cause hyperlucent lungs. – Costophrenic angles should be sharp. Pleural fluid, pleural thickening, or pleural-based mass can blunt these angles. – Diaphragm contours should be noted; flattening of the diaphragms can be suggestive of hyperinflation. • Musculoskeletal – Relevant anatomy: Ribs, sternum, clavicle, scapula, shoulder girdle. – Sternum location should be assessed (pectus excavatum). – Clavicles should be symmetric. – Rib spacing should be symmetrical bilaterally at the respective levels. – Lytic or blastic lesions suggest bony destruction. – Lateral view: Vertebral body heights to exclude compression fractures. • Gastrointestinal – Relevant anatomy: Esophagus, stomach. – An air-fluid level in the mediastinum can result from achalasia or distal esophageal obstruction from cancer. – Lateral view: Assess the posterior cardiac shadow for an air-fluid collection which can represent a hiatal hernia. – An enlarged esophagus can stretch its outer borders beyond the heart, mimicking a

widened mediastinum. – Free air beneath the diaphragm. The stomach bubble is on the left and has a normal appearance of air. Gas in the liver can be suggestive of dead bowel (necrotizing enterocolitis).

PHYSIOLOGY/PATHOPHYSIOLOGY

• Chronic obstructive pulmonary disease (COPD) – Findings: Hyperinflated “black" lungs, large pulmonary arteries that quickly taper, diminished heart size. – Lack of pulmonary vascularity in both lungs is due to pulmonary blebs. The relative hypovascularization creates the black appearance. Asymmetry of the mediastinal contour can be suggestive of cancer. The heart may appear to be smaller because of increased intrathoracic pressure. • Partial pneumothorax – Findings: Absence of lung markings to the periphery, visceral pleural line demarcating lung tissue from air, commonly seen in apex. – In normal lungs, the visceral pleura approximates with the parietal pleura. In a partial pneumothorax, air comes between the visceral and parietal pleura, allowing the border of the parietal pleura to be visualized. An upright film is more sensitive than supine in detecting partial pneumothorax (collects at apex due to gravity). – The entire clinical picture must be taken into account. Generally, a stable patient with a small partial pneumothorax can be observed with serial CXR to confirm resolution. • Tension pneumothorax – Findings: Complete lucency of the chest with shifting of the mediastinum away from the affected side, possible lucency in soft tissues of the neck and axilla. – One-way valve physiology allows air to enter the chest cavity but not escape. The increasing pressure pushes the trachea and mediastinal structures to the contralateral side. – Treatment requires emergent needle decompression at the second intercostal space, midaxillary line. Do not wait for CXR in an unstable patient. • Widened mediastinum – Findings: Mediastinum wider than 8 cm on a standard PA film. Note: a diseased mediastinum may appear <8 cm due to lung hyperinflation or radiological artifact. Alternatively, the supine position can produce an engorged SVC that may mimic a widened mediastinum (if possible, attain an upright CXR to minimize this artifact). – The differential diagnosis includes: Aortic aneurysm, lymphadenopathy, traumatic aortic dissection, mediastinal mass. Mediastinal masses can be further divided into superior (thyroid cancer, lymphoma, teratoma), anterior (thymoma, lymphoma), middle (carcinoma, lymphoma, esophageal rupture, mediastinal fluid, cardiac tamponade), and posterior (esophageal cancer, neurogenic tumors, vertebral trauma) locations. • Lung carcinoma – Findings: Pulmonary nodule, spiculated mass, multiple masses. – Multiple masses in lungs suggest metastases or septic pulmonary emboli, especially in conjunction with cavitation. – Assess the mediastinum for contour and hilar enlargement. • Heart failure

– Findings: Pulmonary edema, enlarged pulmonary vasculature, cephalization of blood flow, increased interstitial markings, enlargement of cardiac silhouette, pulmonary vascular enlargement, loss of contour of cardiophrenic angle. • Pulmonary edema – Findings: Kerley B lines (∼2 cm lines perpendicular to the chest wall), interstitial edema, cardiomegaly, basilar involvement (gravity causes the lower regions of the lung to receive higher blood flow), distended SVC. – It is difficult to distinguish between cardiogenic (hydrostatic) and non-cardiogenic (permeability) pulmonary edema on CXR. • Acute respiratory distress syndrome (ARDS) – Findings: Extensive bilateral opacities and air bronchograms. – Air bronchograms are pathological conditions that result from increased edema in the surrounding lung tissue making it appear "whiter" than normal. This causes the border between air and tissue to appear particularly sharp. Normally, there is a relatively small difference in contrast between the black appearing air in the conducting airways and the white appearing surrounding lung tissue. – Difficult to differentiate between pneumonia, edema, and ARDS; especially with diffuse lung involvement. Pneumonia is usually lobar and unilateral. – Therapeutic positive pressure ventilation can give the appearance of improvement on CXR in ARDS and inaccurately suggest that the patient is ready for weaning off the ventilator. • Abdominal free air – Findings: Air beneath the right hemidiaphragm is often suggestive of abdominal free air. This is best observed on an upright CXR. • Achalasia – Findings: Air–fluid level in mediastinum. Prominent esophageal stripe can mimic the appearance of a widened mediastinum. • Lung calcifications – Findings: Almost always an indicator of a benign nodule. – Previously healed granulomatous disease (histoplasmosis, treated infection, or tumor). • Aspiration pneumonitis – Findings: Initially, the CXR appears normal. Hours later a change in density, usually in the right lower lobe, appears. • Negative pressure pulmonary edema – Findings: Extensive bilateral opacities suggesting alveolar fluid. • Foreign body – Trachea findings: If a ball valve mechanism is present, will see hyperinflation. If simple obstruction is present, will see alveolar collapse. – Esophageal findings: Difficult to see with PA or AP view. Lateral view may provide additional information.

PERIOPERATIVE RELEVANCE

• Preoperative CXR – The American Society of Anesthesiologists Task Force recommendations state that chest radiograph abnormalities may be higher in smokers, patients with recent upper respiratory infection, COPD, and cardiac disease. However, they assert that extremes in

age, smoking, stable COPD, stable cardiac disease, or resolved recent upper respiratory infection do not necessarily constitute an indication for CXR (4). – If a CXR finding is believed to change the management of the anesthetic, it may be considered. – Pacemaker or ICD type and presence can be assessed and confirmed. Also, confirm the absence of a pneumothorax, check the position of the leads to ensure that they are in the cardiac silhouette (right atrium, right ventricle), and look for fluid collection around the device. – Lines and tubes. Follow each line and tube in its entirety. It may be necessary to order additional radiological studies if the line or tube disappears from the borders of the CXR. Assess for pneumothorax and hemothorax. • Intraoperative – Line and tube placement, acute pulmonary changes. – Retained surgical instruments: Order radiological study to cover areas of open or previously open cavities. • Postoperative CXR – Line and tube placement, pulmonary status, endotracheal tube (2 cm above carina). – Atelectasis: Volume loss, with shifting of the mediastinum and bronchus towards the area of collapse. Changes are often subtle and difficult to appreciate.

Pregnancy Considerations

Chest radiographs use a relatively low amount of radiation, but the benefits of the study must be weighed against the risks of ionizing radiation to the embryo or fetus.

REFERENCES

1. Gibbs JM, Chandrasekhar CA, Ferguson EC, et al. Lines and stripes: Where did they go?— From conventional radiography to CT. Radiographics. 2007;27(1):33–38. 2. Beres RA, Goodman LR. Pneumothorax: Detection with upright versus decubitus radiography. Radiology. 1993;186:19–22. 3. Lim EHL, Liu EHC. Preoperative chest X-rays and ECGs: A prospective audit. Singapore Med J. 2003;44(7):340–343. 4. Practice Advisory for Preanesthesia Evaluation. A report by the American Society of Anesthesiologists Task Force on preanesthesia evaluation. Anesthesiology. 2002;96:485– 496.

ADDITIONAL READING

• Ouelette H, Tetreault.: Clinical Radiology Made Ridiculously Simple (2008).

See Also (Topic, Algorithm, Electronic Media Element) • Radiation safety • Acute respiratory distress syndrome • Pneumothorax • Negative pressure pulmonary edema

• Aspiration

CLINICAL PEARLS

• The tip of the central line should ideally sit at the junction of the SVC and right atrium. • Lateral decubitus films can help the physician determine if there is layering of pleural fluid versus a loculated infusion. • Mucous plugging can occur in ventilated patients and appears as a hyperlucency or complete collapse on the affected side. In experienced clinicians often perceive the normal side that has a relatively whiter appearance to be diseased. • Confirmation of pyloric or postpyloric tube for enteral nutrition; make sure the tube is below the diaphragm and do not confuse nasal or oral gastric tube with a feeding tube.

CHLORIDE

Amy Barulic, BS, MHS

BASICS DESCRIPTION • Chloride ions (Cl−) are formed when elemental chlorine accumulates one electron. Chloride can also be found in compound form by covalent bonds. • Cl− is an abundant anion found in the intracellular and extracellular compartments. It functions primarily in the roles of metabolism, acid–base balance, and maintenance of electroneutrality. Normal blood reference range of chloride for most adults is 95–105 mEq/L. • Medications and anesthetics (diuretics, gastrointestinal drugs, propofol, etomidate, and benzodiazepines) that influence Cl− levels are of perioperative concern and relevance.

PHYSIOLOGY PRINCIPLES

• Cerebrospinal fluid (CSF). Secretion of fluid into the ventricles by the choroid plexus depends on active transport of sodium ions (Na+) through the epithelial cells that line the outside of the plexus. Sodium ions “carry” large amounts of Cl− to maintain electroneutrality. The two ions, when combined, increase the quantity of osmotically active ions in the CSF, which in turn causes osmosis of water through the membrane. Less important transport processes move small amounts of glucose into the CSF while moving both potassium and bicarbonate ions out, and into the capillaries, thus concentrating Cl− (the [Cl−] is ∼15% greater in the CSF as compared to the plasma). • Neuronal resting membrane potential. Cl− is maintained in high concentration in the extracellular fluid compared to the intracellular environment of the neuron (via the semipermeable bilayer lipid membrane in combination with active transport processes). The Cl− gradient (107 mEq/L extracellularly and 8 mEq/L intracellularly) yields a Nernst potential of –70 mV inside the neuron that is only slightly more negative than the actual measured value of –65 mV (major contributor). • GABA (gamma-aminobutyric acid). Functions as a chief inhibitory neurotransmitter in the CNS to regulate neuronal excitability. GABA receptors are ligand-activated, chloride channels and bind GABA neurotransmitter and several other drugs (hypnotics, benzodiazepines, etc.). When an agonist binds, Cl- channels open and ions flow down their concentration gradient and enter the cell; this results in hyperpolarization (cell becomes more negative). By further decreasing the membrane resting potential, the ability for an action potential to be reached is also decreased. • Stomach. The tubular, oxyntic glands are composed of parietal cells and are located on the inside surfaces of the body and fundus of the stomach. When stimulated, parietal cells secrete an acidic solution (at their villus-like projections) that contains 160 mmol/L of HCl, which is nearly isotonic to body fluid but has a pH of ∼0.8. The rate of formation and

secretion of HCl by the parietal cells is directly related to the amount of histamine secreted by the enterochromaffin-like cells (ECL cells) that lie in the deep recesses of the oxyntic glands. • Kidneys – Following glomerular filtration, the filtrate enters the proximal convoluted tubule (PCT) of the nephron. The epithelial cells in the first half of the PCT are highly permeable to most ions and are responsible for ∼70% of Na+ (via a Na+/K+ ATPase antiporter), as well as significant water, urea, organic acid, H+, HCO3−, Cl−, and phosphate reabsorption. When

Na+ is reabsorbed, negative ions “follow” to maintain electroneutrality; they passively diffuse through paracellular pathways and are also reabsorbed via secondary active transport with Na+ across the luminal membrane. – The lumen of the nephron in the second half of the PCT has a relatively high concentration of chloride (∼140 mEq/L) as compared to the early proximal tubule (∼105 mEq/L). This higher concentration favors diffusion of ions through intercellular junctions and into the renal interstitial fluid. – As the PCT enters the hyperosmotic medulla, it becomes narrower and eventually forms the Loop of Henle. Electrolytes are actively transported out of the lumen to create a concentration gradient in the renal medulla; consequently, the epithelial cells have a high metabolic rate. Approximately 25% of the filtered load of Cl− is reabsorbed here • Blood/plasma. Carbonic acid (H2CO3), formed in red blood cells (RBCs), dissociates with hydrogen (H+) and bicarbonate ions (HCO3−).

– The H+ remains within the RBC and reversibly binds to hemoglobin (Hg) thus, the Hg molecule functions as an acid–base buffer. – The HCO3− diffuses out of the RBC and into the plasma, while Cl− diffuses into the cells

to maintain electroneutrality; this occurs via the bicarbonate–chloride carrier protein that is embedded in the membrane. – As a consequence, the chloride content of venous RBCs is greater than that of arterial red cells. This is referred to as “chloride shifting.” • Sweat secretions. The secretory portion of the sweat gland secretes a fluid called the primary secretion or precursor secretion; the concentration of the ion constituents is then modified as the fluid flows through the duct. – The precursor secretion composition is similar to that of plasma (minus the plasma proteins), with a Cl− concentration of ∼104 mEq/L. – As this precursor solution flows through the duct portion of the gland, it is modified by reabsorption of most of the sodium and Cl− – The autonomic nervous system, and hence, the rate of sweating, determines the tonicity of the sweat. A slight stimulation can result in a near complete reabsorption of sodium and chloride with a resultant concentration as low as 5 mEq/L (hypotonic sweat). Alternatively, a strong sympathetic stimulation aims to preserve water, and results in a hypertonic sweat (∼50–60 mEq/L).

DISEASE/PATHOPHYSIOLOGY

• Hyperchloremia is defined as an elevated Cl− plasma concentration (>107–110 mEq/L) and can result from diarrhea, renal disease, hyperchloremic fluid administration, and as a side effect of medications. It can result in impaired blood sugar control in diabetics, muscle weakness, deep and rapid breathing, a nongap metabolic acidosis, and possibly coma. • Hypochloremia is defined as a low Cl− plasma concentration (<95 mEq/L). It is commonly seen with hypokalemia from gastrointestinal losses (vomiting, diarrhea, nasogastric suctioning); potassium binds with chloride (KCl). Hypochloremia may result in muscle hypertonicity/tetany, shallow and depressed breathing, and metabolic alkalosis. • Cystic fibrosis (CF) is an autosomal-recessive disease caused by a mutation in the CFTR gene that impairs Cl− transport and has multiple organ system involvement. – The primary source of morbidity and mortality is due to the progressive nature of obstructive pulmonary disease characterized by chronic inflammation, infection, and destruction of airways. • Bartter’s syndrome is characterized by the defective transport of Cl− in the thick ascending Loop of Henle, resulting in salt wasting, metabolic alkalosis, and hypokalemia. It is a rare genetic condition.

PERIOPERATIVE RELEVANCE

• Iatrogenic fluid administration. The infusion of large amounts of saline-based solutions can result in hyperchloremia. Normal saline has a [Cl−] of 154 mEq/L; additionally, albumin and hydroxyethyl starch solutions (Hetastarch) are prepared in a normal saline solution. A hyperchloremic, nongap, metabolic acidosis can result, initially from dilution of HCO3-. Ultimately, however, HCO3- anion is eliminated by the kidneys in order to maintain

electroneutrality (increased chloride anion load). Clinical consequences of the metabolic acidosis are unclear. However, attempts at correcting the abnormality may actually cause more issues (iatrogenic causes such as administering additional hyperchloremic crystalloids). • Mannitol has been shown to reduce the viscosity of mucus in patients with CF and is currently being examined for the treatment of CF and bronchiectasis. When inhaled as a dry powder orally, it osmotically draws water into the lungs and thins the mucus. This may also facilitate coughing as an expectorant during physiotherapy. • Loop diuretics (furosemide, bumetanide, torsemide) are competitive antagonists at the Cl− binding site on the luminal surface of the PCT. This results in impaired Na+ reabsorption and increased urine output (natriuresis). Additionally, the hyperosmotic medulla created by the countercurrent exchange is hindered. • Thiazide diuretics (hydrochlorothiazide) are secreted into the PCT from the bloodstream and selectively inhibit Na+–K+−Cl− transporters in the distal convoluted tubule. This results in impaired Na+ and Cl− reabsorption and increased urine output (natriuresis). • Antacids are orally ingested, inorganic salts that release anions on dissolving in acidic gastric secretions. The anions combine and neutralize hydrochloric acid immediately; they do not affect gastric pH. • H2 antagonists are competitive, as well as inverse, antagonists at H2 receptors of gastric parietal cells. Consequently, they decrease baseline parietal cell acid and volume secretion

as well as blunt the response to normal stimuli, which subsequently inactivates pepsin and stimulates gastrin release. • Propofol, etomidate, and benzodiazepines potentiate GABA receptor binding by attaching to the beta subunit of the GABAA receptor; thus it facilitates an inhibitory response by hyperpolarizing the cell membrane.

EQUATIONS

Plasma anion gap (mEq/L) = [Na+] – ([HCO3−] + [Cl−])

REFERENCES

1. Base EM, Standl T, Lassnigg A, et al. Efficacy and safety of hydroxyethyl starch 6% 130/0.4 in a balanced electrolyte solution (volulyte) during cardiac surgery. J Cardiothorac Vasc Anesth. 2011; 25(3):407–414. 2. onhomme V, Demoitie J, Schaub I, et al. Acid–base status and hemodynamic stability during propofol and sevoflurane-based anesthesia in patients undergoing uncomplicated intracranial surgery. J Neurosurg Anesthesiol. 2009;21(2):112–119. 3. arcia J, Roure P, Hayem C, et al. Bronchial endoscopy under local anesthesia and pain in children. The value of a nitrous oxide-oxygen combination. Rev Mal Respir. 1998;15(2):179–183. 4. Kim JY, Lee D, Lee KC, et al. Stewart’s physiochemical approach in neurosurgical patients with hyperchloremic metabolic acidosis during propofol anesthesia. J Neurosurg Anesthesiol. 2008;20(1):1–7. 5. Scheingraber S, Rehm M, Sehmisch C, et al. Rapid saline infusion produces hyperchloremic acidosis in patients undergoing gynecologic surgery. Anesthesiology. 1999;90(5):1265– 1270. 6. Shangraw RE, Winter R, Hromco J, et al. Amelioration of lactic acidosis with dichloroacetate during liver transplantation in humans. Anesthesiology. 1994;81(5):1127– 1138. 7. Wheeler DW, Thompson AJ, Corletto F, et al. Anaesthetic impairment of immune function is mediated via GABA(A) receptors. PLoS One. 2011;6(2):317152. 8. ordsworth AE, McDonald A, Lacy D, et al. Bronchial lavage in cystic fibrosis patients during general anaesthesia for elective surgery. Tenth Annual North American Cystic Fibrosis Conference. 1996;362:309. See Also (Topic, Algorithm, Electronic Media Element) • Cystic fibrosis • Aspiration • Hyperchloremic nongap metabolic acidosis • Propofol infusion syndrome

CLINICAL PEARLS

• Large infusions of anesthetics such as propofol and isoflurane can result in metabolic acidosis. • Large administration of saline during intraoperative care can result in a nongap, hyperchloremic, metabolic acidosis.

CHOLECYSTECTOMY Sulin G. Yao, MD Calvin Lyons, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION General

• Surgical removal of the gallbladder, open or laparoscopic, for treatment of symptomatic cholelithiasis (stones in the biliary tract resulting in mechanical obstruction), cholecystitis (inflammation of gallbladder secondary to obstruction of cystic duct), or gallbladder cancer. • Open cholecystectomy – Resection from the liver and isolation of the cystic duct and artery are performed. – Chosen for patients with significant inflammation, intraabdominal adhesions, coagulopathies, known gallbladder cancer, or the inability to tolerate laparoscopic procedures. – Laparoscopic approach may be converted to an open approach if technically difficult. • Laparoscopic cholecystectomy – Four trochars are inserted to pass instruments; one in the umbilicus and three in the right upper quadrant (RUQ). – A pneumoperitoneum is created to aid with visualization; insufflation is done with carbon dioxide (CO2) at pressures of 10–15 mm Hg.

– Following resection from the liver and isolation of the cystic duct and artery, the gallbladder is detached via cauterization, clipping, or stapling. – The gallbladder is placed in a bag and removed through the trocar site in the abdominal wall. • Cholangiograms (injection of contrast dye via a catheter in the cystic duct) can be performed intraoperatively to detect gallstones in the cystic duct (choledocholithiasis). An absence of spread/filling on radiography indicates that a stone is present. Some surgeons use ultrasound in place of cholangiograms. • Common bile duct exploration is performed via a small incision (choledochotomy). A fiberoptic scope (choledoscope) is passed through the incision to aid in visualization. Position

Supine; reverse Trendelenburg with right side up to displace bowel (laparoscopic and open procedures) Incision

• Laparoscopy: 5–7 mm incisions for the insertion of trocars. Supraumbilical, epigastric, midclavicular, and anterior axillary ports are most frequently placed. • Open: Right subcostal approach or upper midline (less common) 5–7 inches.

Approximate Time

20–60 minutes; intraoperative cholangiogram may add 10–20 minutes. EBL Expected

• Open cholecystectomy: <250 mL • Laparoscopic: Minimal EBL

Hospital Stay

• Some ambulatory centers discharge the same day after careful observation. • Complicated cases may require 1 day hospitalization or longer.

Special Equipment for Surgery

• Laparoscopic equipment • Possible fluoroscopy for cholangiogram

EPIDEMIOLOGY Prevalence

• In the US, ~500,000 cholecystectomies are performed each year. • 10% of the US adult population has cholelithiasis; 20% over the age of 40 years, and 30% over the age of 70 years. (1)[A]. • Urgent laparoscopic conversion rate: <15% • Elective laparoscopic conversion rate: <5%

Prevalence

• Mostly adults, increases with age • Female to male ratio 4:1 during reproductive years; ratio narrows as age increases (1)[A]. • Risk factors: Obesity, diabetes mellitus, estrogen, pregnancy, hemolytic diseases, and cirrhosis. • “Fat, Female, Fertile, Forty” is a pneumonic used to describe patients prone to cholelithiasis.

Morbidity

• Hemorrhage, bile leak, perforation of gallbladder, common bile duct injury, retained bile duct stones. • Open cholecystectomy morbidity rate is 3.3 times more than that for laparoscopic cholecystectomy (2)[A]. This may be a function of the selection criteria of patients needing an open procedure.

Mortality

• Standardized mortality ratio (SMR) within 90 days for open cholecystectomy is 3.89. • SMR within 90 days for laparoscopic cholecystectomy is 0.73 (2)[A].

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess for the possibility of a “full stomach.” • Determine volume status and rule out electrolyte abnormalities. Increased abdominal pressure from insufflation and reverse Trendelenburg can cause hemodynamic compromise.

• Evaluate respiratory function: Open cholecystectomy will have post-op splinting and impaired respiratory function due to incision; consider epidural for post-op pain management. • Cirrhotics require careful assessment and optimization of their disease prior to surgical intervention.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Epigastric/RUQ pain, nausea, vomiting • Toxicity: Fever and diaphoresis

History

• Duration of symptoms • Oral intake, quantity and quality of urine • Last menstrual cycle in women of child-bearing age

Signs/Physical Exam

• Tachycardia, hypotension, and jaundice • Guarding or rebound with acute cholecystitis; otherwise, normal abdominal exam with mild tenderness. • Fluid status: Capillary refill, mucus membranes, urine output, lethargy, and orthostatic BPs.

MEDICATIONS

Gastric medication

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• White count to rule out infection • Cirrhotic patients: Consider coagulation profile, albumin, and hemoglobin. • Abdominal ultrasound is the test of choice for diagnosis of cholelithiasis: 90–95% sensitive (1)[A].

CONCOMITANT ORGAN DYSFUNCTION

• Diabetes mellitus, ileal disease, hemolytic disorders, choledocholithiasis, cholangitis, or active pancreatitis. • Cirrhotics have an increased incidence of biliary tract disease. • Pregnancy is usually delayed until delivery of fetus unless acute cholecystitis presents.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Patients at risk for gastric aspiration: Give H2 blockers, antacids, promotility, or proton pump inhibitors. • Nasogastric tube may be considered. • Fluid resuscitation as appropriate prior to induction. • Transfusion of fresh frozen plasma or other blood products as appropriate in cirrhotics. • If pain medication needed, meperidine may cause less Sphincter of Oddi spasm than other opiates.

Special Concerns for Informed Consent

• Surgeons consent for the potential to convert to an open procedure. • Open procedures may benefit from an epidural for postoperative pain management.

Antibiotics/Common Organisms

• Indicated for acute cholecystitis and/or cholangitis; should cover gram-negative aerobes (Escherichia coli, Klebsiella) as well as anaerobes (Bacteroides species) • Third-generation cephalosporins (ceftriaxone) with good anaerobic coverage or a secondgeneration cephalosporin (cefuroxime or cefotetan) combined with metronidazole is a typical regimen. • Cephalosporin allergy: Aminoglycoside and metronidazole.

INTRAOPERATIVE CARE Choice of Anesthesia

• Laparoscopic technique: General endotracheal anesthesia with a cuffed tube allows for positive pressure ventilation, muscle relaxation, protection against aspiration, and minimizes hypercarbia from absorbed CO2. These same requirements preclude the use of

laryngeal mask airway (LMA); GETA can also generate greater positive pressure (reduced compliance requires higher peak inspiratory pressures) that LMA use cannot. As a sole anesthetic technique, an epidural/spinal is not ideal because it requires a high block/level. If performed, consider supplementing with nitrous oxide and keeping insufflation pressures <10 mm Hg. • Open technique: Epidural anesthesia may be utilized for open procedures in conjunction with GETA.

Monitors

• Standard ASA monitors • Invasive hemodynamic monitoring may be needed for ASAIII–IV patients. • Foley catheter is a surgical preference.

Induction/Airway Management

Rapid sequence induction if not NPO; also consider other risks for aspiration (nausea, vomiting, narcotic use, gastroesophageal reflux). Maintenance

• Orogastric/nasogastric tube placement allows for suctioning of gastric and biliary juices and

decompressing the stomach to facilitate laparoscopic visualization. • Balanced anesthetic with volatile or total intravenous anesthetic. • Muscle relaxation facilitates resection for laparoscopic and open procedures. • Vagal episodes can occur when a pneumoperitoneum is instituted; it typically resolves immediately with desufflation. • Opioids may cause Sphincter of Oddi spasm; theoretically, meperidine has a reduced incidence. • Reverse Trendelenburg affects the cardiopulmonary system – Cardiac: Preload to the right atrium is reduced due to gravity; this effect can be exacerbated in patients who are volume depleted. – Pulmonary: Parameters are usually improved due to increased compliance and functional residual capacity. • Laparoscopic-induced pneumoperitoneum in the reverse Trendelenburg position affects the cardiopulmonary systems: – Cardiac: Preload to the right atrium is further decreased; pneumoperitoneum pressures are often equal to or greater than right atrial filling pressures. – Pulmonary: Reverse Trendelenburg position initially improves pulmonary mechanics, but pneumoperitoneum reduces pulmonary compliance and functional residual capacity; may need to adjust ventilator settings. Use of CO2 for insufflation can increase PaCO2 unless the tidal volume or respiratory rate is increased.

Extubation/Emergence

• Give prophylactic antiemetics prior to extubation. • Bile is an emetic and caustic; suction the gastric tube prior to extubation. • Patient should be awake and capable of protecting their airway.

FOLLOW-UP BED ACUITY

Pulmonary dysfunction may be greater with patients undergoing open procedures. ANALGESIA

• Reduced pain with laparoscopic procedure. • Shoulder pain may be more effectively treated with ketorolac. • Epidural catheters may be considered in open procedures; however, the open technique is often performed in cirrhotics, thus, need to confirm coagulation profile prior to placement.

COMPLICATIONS

• Pancreatitis, bowel injury, bile duct injury, or bile leak, pneumothorax, atelectasis. • Shoulder pain with laparoscopic procedures, due to C3,4,5 irritation • Hemorrhage • Postcholecystectomy syndrome: Continued pain after cholecystectomy.

PROGNOSIS

• 15.2% postcholecystectomy patients continue with postoperative abdominal pain. • 5.6% with continued vomiting. • 40.2% with gas/flatulence (3)[A].

REFERENCES

1. chirmer BD, Winters KL, Edlich RF. Cholelithiasis and cholecystitis. J Long Term Eff Med Implants. 2005;15(3):329–338. 2. Zacks SL, Sandler RS, Rutledge R, et al. A population-based cohort study comparing laparoscopic cholecystectomy and open cholecystectomy. Am J Gastroenterol. 2002;97(2):334–340. 3. Weinert CR, Arnett D, Jacobs D Jr, et al. Relationship between persistence of abdominal symptoms and successful outcome after cholecystectomy. Arch Intern Med. 2000;160(7):989–995. 4. Di Sebastiano N, Bonetti L, Boninsegni P, et al. Respiratory mechanics and gas exchange in anesthesia for laparoscopic cholecystectomy. Minerva Anesthesiol. 1993;59(10):487–492. 5. Girardis M, DaBroi U, Antonutto G, et al. The effect of laparoscopic cholecystectomy on cardiovascular function and pulmonary gas exchange. Anesthes Analges. 1996;83(1):134– 140. 6. Suh MK, Seong KW, Jung SH, et al. The effect of pneumoperitoneum and Trendelenburg position on respiratory mechanics during pelviscopic surgery. Korean J Anesthesiol. 2010;59(5):329–334.

ADDITIONAL READING

• Rist M, Hemmerling TM, Rauh R, et al. Influence of pneumoperitoneum and patient positioning on preload and splanchnic blood volume in laparoscopic surgery of the lower abdomen. J Clin Anesth. 2001;13(4):244–249.

See Also (Topic, Algorithm, Electronic Media Element) • Laparoscopy • Cirrhosis

CLINICAL PEARLS

• Laparoscopic cholecystectomy is the preferred technique for gallbladder removal. Benefits include small incision, and reduced instances of postoperative pain, incisional hernias, wound infections, respiratory compromise, and quicker discharge to home due to quicker return of ambulation. • Consider possible laparoscopic-related effects on IVF status, gastric regurgitation, increased airway resistance, possible venous embolism, and expect an increase in ETCO2. • Significant ETCO2 increase may be due to subcutaneous emphysema; it is rapidly absorbed but problematic for pulmonary-compromised patients who are already extubated.

CHRONIC ANGINA Piotr K. Janicki, MD, PhD Marek Postula, MD, PhD

BASICS DESCRIPTION

• Stable angina is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved by rest or nitroglycerin. • Chronic angina – Does not increase in frequency or severity, and is predictable in nature. – May be associated with ST segment depression on ECG. – May occur in patients with seemingly normal coronary arteries subjected to acute or chronic increases in myocardial work. • Coronary artery spasm can provoke pain in the absence of increased myocardial demands such as variant (Prinzmetal’s) angina and some cases of stable or unstable angina. Incidence

• New and recurrent coronary attack in the US: 1,255,000/year • Approximately 34% of people, who experience a coronary attack in a given year, die from it.

Prevalence

• 17.6 million people in the US have coronary heart disease (CHD; of which 10.2 million persons have angina pectoris, and 8.5 million have experienced a myocardial infarction (MI). • The estimated age-adjusted prevalence of angina in women age 20 years and older was 4.5% for non-Hispanic white women, 5.4% for non-Hispanic black women, and 4.8% for MexicanAmerican women. Rates for men in these three groups were 4.7%, 4.0%, and 2.9%, respectively. Morbidity

• New cases of stable angina: ∼500,000 new cases/year (Framingham Heart Study, National Heart, Lung, and Blood Institute). • About 10% of patients/year with stable angina will develop worsening symptoms that require revascularization. Mortality

• In the US in 2006 there were 425,425 deaths from coronary artery disease (CAD) (about 1 of every 6 deaths) and overall death rate from cardiovascular disease was 262.5 per 100,000 persons. • The death rate is as follows: – Greater in men (3 times higher at ages 25–34 years and, falling to 1.6 times at ages 75–84

years). – Greater in blacks compared to whites, an excess that disappears by age 75. Among the Hispanic population, coronary mortality is not as high as it is among blacks and whites. • A perioperative MI has been associated with a 30–50% perioperative mortality and reduced long-term survival. • The most frequent causes of angina are as follows: coronary atherosclerosis, coronary artery vasospasm, fibrosis, embolism, dissection, and arteritis. • Nonmodifiable risk factors: Age, family history, and male gender. • Modifiable risk factors: Cigarette smoking, hypertension, dyslipidemia, diabetes, chronic kidney disease, obesity, and physical inactivity. • Myocardial ischemia is caused by an imbalance between myocardial oxygen supply and myocardial oxygen consumption. • Myocardial oxygen supply is determined by arterial oxygen saturation and coronary flow that is dependent on the luminal cross-sectional area of the coronary artery and coronary arteriolar tone. Atherosclerotic plaques may dramatically decrease both the cross-sectional area and coronary artery tone. When combined with increased oxygen demand from tachycardia, increased myocardial contractility and wall stress, the oxygen supply may become inadequate. • Ischemia reduces the formation of adenosine triphosphate (ATP), an oxygen-dependent process. This results in the development of lactic acidosis, loss of the normal Na+/K+ ATPase pump, impaired myocardial membrane integrity, and release of chemical substances that stimulate chemosensitive and mechanoreceptive receptors within cardiac muscle fibers and around the coronary vessel. • The primary mediator of angina is adenosine, via stimulation of the A1 adenosine receptor.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperative assessment should assess current myocardial function and if there is myocardium at risk for ischemia; a relevant clinical history may warrant further testing (1). • Ensure an adequate myocardial oxygen supply: Assess hemoglobin, diastolic perfusion pressure, oxygen saturation, and adequate diastolic time (low heart rate; HR). • Avoid increases in myocardial oxygen demand: Assess HR, myocardial contractility, afterload, and preload.

PREOPERATIVE ASSESSMENT • Characterized as a discomfort rather than pain, and may be difficult to describe. • Location is most commonly felt beneath the sternum, but can vary. Radiation may occur to the left shoulder and down the inside of the left arm, even to the fingers; straight through to the back; into the throat, jaws, and teeth; and, occasionally, down the inside of the right arm. It may also be felt in the upper abdomen. • Onset and offset is typically gradual; the intensity of the discomfort increases and decreases over several minutes. • Provoking factors: Physical activity, cold, emotional stress, sexual intercourse, meals, or lying down (which results in an increase in venous return and increase in wall stress).

• Duration: Generally lasts for 2–5 minutes unless the patient is experiencing an acute coronary syndrome, especially MI. • Relief: Symptoms usually subside with rest. • Associated symptoms include shortness of breath, belching, nausea, indigestion, diaphoresis, dizziness, lightheadedness, clamminess, and fatigue.

• Information about the character and location of discomfort, radiation, associated symptoms, and precipitating, exacerbating, or alleviating factors. • A complete inventory of comorbid conditions, including cardiac risk factors and family history. • Tachycardia due to reflex sympathetic nervous system activation and in response to discomfort. • Elevated BP • Heart sounds: The 2nd heart sound may become paradoxical because left ventricular (LV) ejection is more prolonged during an ischemic attack; a 4th heart sound is common, and a 3rd heart sound may develop. • Murmurs: A mid- or late-systolic apical murmur (shrill or blowing but not especially loud) may occur if ischemia causes localized papillary muscle dysfunction, producing mitral regurgitation. • Precordial pulsation: Palpation of the chest wall may reveal abnormal pulsations that correlate with transient dysfunction. TREATMENT HISTORY

• Coronary angiography • Revascularization • Percutaneous coronary intervention (PCI) • Coronary artery bypass grafting (CABG) • Implanted pacemakers and defibrillation devices

MEDICATIONS

• Antianginal therapy – Nitrates: Anti-ischemic efficacy pertains to their ability to decrease myocardial oxygen demand as a result of systemic vasodilatation rather than as a coronary vasodilator. – Beta-blockers: Relieve anginal symptoms by reducing both HR and contractility. – Calcium channel blockers: Improve anginal symptomatology by coronary and peripheral vasodilatation and by reducing contractility. • Additional treatment – ACE inhibitors: Recommended for patients with stable angina pectoris and coexisting hypertension, diabetes, heart failure, asymptomatic LV dysfunction, or post-MI. – Angiotensin receptor blockers (ARBs): Recommended for patients who have hypertension, heart failure; indications for, but an inability to tolerate ACE inhibitors; or have had an MI with LV ejection fraction ≤40%. – Statins • Antiplatelet drugs – Aspirin: The optimal antithrombotic dosage of aspirin appears to be 75–162 mg/day.

– Clopidogrel: An alternative for patients who are allergic to aspirin.

• Laboratory tests: CBC, hemoglobin, Cr, fasting glucose, markers of myocardial damage if evaluation suggests clinical instability. • Resting 12-lead ECG (normal in ∼50% of patients with chronic stable angina): – In patients with at least 1 clinical risk factor, who are undergoing vascular surgical procedures. – In patients with known CHD, peripheral arterial disease, or cerebrovascular disease who are undergoing intermediate-risk surgical procedures. • Chest radiography • Exercise and stress tests are performed when there is suspicion that the myocardium is at risk for ischemia. • Dobutamine stress ECG or stress cardiac imaging (intravenous dipyridamole/adenosine myocardial perfusion imaging with both thallium-201 and technetium-99m) in patients who cannot exercise.

CONCOMITANT ORGAN DYSFUNCTION • Congestive heart failure • Arrhythmias

CIRCUMSTANCES TO DELAY/ CONDITIONS

• ST segment changes on ECG • Symptoms of worsened, or decompensated heart failure • Symptoms of increased activation of the adrenergic system: Elevated BP and increased HR • Supraventricular or ventricular arrhythmias with hemodynamic instability

CLASSIFICATIONS

• Canadian Cardiovascular Society Angina Classification – Class 0: Asymptomatic – Class 1: Angina with strenuous exercise – Class 2: Angina with moderate exertion – Class 3: Angina with mild exertion Walking 1–2 level blocks at normal pace Climbing 1 flight of stairs at normal pace – Class 4: Angina at any level of physical exertion

TREATMENT Premedications

Anxiolytics may be indicated to decrease anxiety and the associated increase in cardiac oxygen demand (tachycardia, hypertension). Choice of Anesthesia

• All inhaled volatile anesthetic agents have some cardiovascular effects, including depression of myocardial contractility and afterload reduction.

• Neuraxial anesthetic techniques can cause sympathetic blockade, resulting in decreases in both preload and afterload.

Monitors

• Standard ASA monitors • ECG analysis of the ST segment in multiple leads (i.e., II, V4, and/or V5) • Arterial line may be considered • Transesophageal echocardiography (TEE) may be considered

Induction/Airway Management

During induction, laryngoscopy, and intubation, maintain hemodynamic stability: Avoid excessive tachycardia, hypertension, hypotension, and drug-induced depression of cardiac function. Maintenance

• Maintenance of anesthesia techniques should target avoidance of cardiac ischemia perioperatively (caused by increased cardiac oxygen demand or decreased oxygen supply). • Intraoperative ischemia management – Increased oxygen demand Increased HR: Beta-blockers and analgesics Increased BP: Deepen anesthetic, analgesics, and antihypertensives Increased pulmonary capillary wedge pressure (PCWP): Nitroglycerin and diuretics – Decreased oxygen supply Decreased HR: Atropine and pacing Increased HR: Beta-blockers and analgesics Decreased BP: Decrease anesthetic depth and vasoconstrictors Decreased PCWP: Volume and inotropy Blood transfusion if HCT<30% – Avoidance of hypothermia

Extubation/Emergence

Maintenance of hemodynamic stability and avoidance of factors increasing cardiac oxygen demand (shivering, vasoconstriction, pain, agitation).

POSTOPERATIVE CARE BED ACUITY

• Vigilance for chest pain, arrhythmias, and hemodynamic instability • Consider supplemental oxygen (nasal cannula, face mask) • Good pain control • Normothermia

• Perioperative ischemia and/or MI. • Patients with symptomatic MI after surgery have a marked increase in the risk of death (40– 70%). – Postoperative troponin measurement is recommended in patients with ECG changes or

chest pain typical of acute coronary syndrome. • Perioperative arrhythmias and conduction disorders

REFERENCES

1. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice. Circulation. 2007;116:e418–e499. See Also (Topic, Algorithm, Electronic Media Element) • Coronary arteries • Myocardial oxygen demand

CODES ICD9 • 411.1 Intermediate coronary syndrome • 413.1 Prinzmetal angina • 413.9 Other and unspecified angina pectoris ICD10 • I20.0 Unstable angina • I20.1 Angina pectoris with documented spasm • I20.9 Angina pectoris, unspecified

CLINICAL PEARLS

• Cardiovascular complications represent the most common and troublesome adverse consequence of noncardiac surgery. • It is important that the care team responsible for the long-term care of the patient be provided with complete information about any cardiovascular abnormalities or risk factors for CAD identified during the perioperative period.

CHRONIC BRONCHITIS Jennifer Wu, MD, MBA

BASICS • Chronic bronchitis is one of the two types of chronic obstructive pulmonary disease (COPD), the other being emphysema. • Defined as a productive cough > 3 months for two consecutive years. – Additionally, it is characterized by irreversible airway obstruction, chronic airway irritation, hypersecretion of mucus, and bronchial inflammation. – Diagnosis and treatment are guided by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (1). – Varying degrees of emphysematous disease are commonly present. • Postoperatively, patients with chronic bronchitis have an increased risk of bronchospasm, laryngospasm, atelectasis, wheezing, difficulty clearing mucous, and prolonged intubation. Additionally, preoperative pulmonary function tests (PFTs) do not reliably predict postoperative outcome. • In the ambulatory surgery setting, home discharge may be challenging and patients should be carefully selected and screened. • In the US: 10–12 million • Women are twice as likely as men to have chronic bronchitis (2). • Highest prevalence in those >65 years of age

Morbidity

• Treatment costs: $11.7 billion annually • Hospitalizations costs: $6 billion annually

Mortality

• 4th leading cause of death in the US (2). • There is an increased risk of death within 5 years, following an episode of respiratory failure. • Overall mortality is associated with pack-year smoking history (average number of packs of cigarettes per day multiplied by total number of years smoking). • Smoking • Exacerbations can result from respiratory tract infections.

• Cough and chronic mucus production result from immune responses to inhaled toxic particles and gases in cigarette smoke. Inflammation in the epithelium of the central airways and mucous-producing glands result in increased mucous production, reduced mucociliary clearance, and increased permeability of the airspace epithelial barrier (3). – Inflammatory cells release serine proteases that are potent secretagogues for mucous. – Oxidant release from cigarette smoke induces the MUC5AC gene, causing overproduction

of mucin. • During the early stages of COPD, it is unclear what the effects of mucus hypersecretion are. However, in the later stages of the disease, changes become apparent: – Decreases in forced expiratory flow rates due to obstruction. – Increases in residual volume (RV). Air trapping results in progressive hyperinflation with a resultant increase in total lung capacity (TLC) and flattening of diaphragms. – Increases in the residual volume to total lung capacity ratio (RV:TLC). • Airway reactivity may be the result of smoking-induced inflammation or the airway narrowing that occurs with chronic disease (4). • Nonuniform distribution of ventilation causes ventilation/perfusion mismatch and an increase in dead space, leading to carbon dioxide (CO2) retention. Some areas of the lung are underventilated in relation to perfusion because of airway obstruction. Air is forced from these areas to other parts of the lung, causing overventilation relative to perfusion. • Compensatory mechanisms – Compensatory responses of the lungs changes their mechanical behavior. It decreases the tendency for alveoli to collapse and makes atelectasis less likely. – Erythrocytosis, accompanied by an increase in blood viscosity, results from chronic hypoxemia. – Chronic bronchitis “blue bloaters” have hypercarbia with resultant respiratory acidosis, which is metabolically compensated. • Cor pulmonale. Chronic alveolar hypoxemia causes pulmonary hypertension that becomes fixed over time due to changes in the pulmonary arterial vessels. High pressure in the pulmonary circulation causes right ventricular hypertrophy. Chronic findings can include right bundle branch block, right heart strain, and right heart failure.

ANESTHETIC GOALS/GUIDING PRINCIPLES • Assess severity of disease • Optimize pulmonary function • Continue maintenance medications • Treat acute exacerbation • Avoid perioperative bronchospasm

PREOPERATIVE ASSESSMENT • Productive cough • Shortness of breath (SOB)

• Age of onset • Current smoking status • Quality of current cough/mucus • Treatment history – Frequency of exacerbations – Bronchodilator use – Steroid use – ER visits

– Hospitalizations – Intensive care unit (ICU) admissions – Intubations

• Wheezing • Tachypnea • Prolonged expiration • JVD • “Blue bloaters” • Low baseline room air O2 saturation with worsening on exertion. TREATMENT HISTORY

Supplemental O2 is indicated when baseline O2 saturation is <88% or <90% when there are signs of pulmonary hypertension or right heart failure. It is used to maintain PaO2 between

60 and 80 mm Hg and is the only current treatment that reduces mortality. MEDICATIONS

• Corticosteroids – Inhalational route has minimal systemic effects and scheduled dosing has been shown to decrease exacerbations. – Oral route causes more side effects with little improvement in benefit; may be prescribed to treat an acute exacerbation or prophylactically in patients with severe disease prior to a surgical procedure. • Bronchodilators reduce exacerbations and improve symptoms. – Anticholinergics (ipratropium bromide) – Beta-adrenergic agonists (salmeterol, albuterol) • Theophylline is a methylxanthine used to improve ventilation by relaxing bronchial smooth muscle. It is a phosphodiesterase inhibitor and adenosine receptor antagonist. Because of the narrow therapeutic window and adverse cardiac effects, it is used infrequently. High levels can cause tachycardia, arrhythmias, hypotension, and CNS excitation. • Antibiotics are useful in treating acute exacerbations triggered by infection; scheduled, prophylactic antibiotics have not shown benefit. • Bupropion or nicotine replacement • Diuretics for cor pulmonale • Baseline room air O2 saturation

• EKG may show right axis deviation as a result of right ventricular hypertrophy. • Chest x-ray (CXR) should be performed if infection is suspected. May show hyperinflation, bullae, blebs, and increased pulmonary vascular markings. • ABGs (often PaCO2 >45 mm Hg and PaO2 <65 mm Hg) • Sputum sample (neutrophils, bacteria) • Pulmonary function (FEV1/FVC <0.7 and not reversible with bronchodilator) CONCOMITANT ORGAN DYSFUNCTION

• Cor pulmonale • Emphysema

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Acute exacerbation as demonstrated by dyspnea, increased O2 requirement, increased mucous production, fatigue or lethargy, or a PaCO2 increased from baseline (or an acute

respiratory acidosis where metabolic compensation has not yet occurred). • Pneumonia or upper respiratory infection • Pulmonary edema

CLASSIFICATIONS

Based on spirometric measurements. Diagnosis requires an FEV1/FVC ratio <0.7. Severity is

gauged by the postbronchodilator FEV1 (1): • Mild: FEV1 ≥80% predicted

• Moderate: FEV1 50–80% predicted • Severe: FEV1 30–50% predicted • Very severe: <30% predicted

TREATMENT Premedications

• Antibiotics if sputum quality or quantity suggests infection. • Bronchodilator use for symptom improvement should be continued perioperatively via puffs or nebulizer. • Inhaled corticosteroids should be continued. • Smoking cessation for any length of time is beneficial, but optimally should be initiated 8 weeks before surgery. Abrupt discontinuation may actually increase mucus production. • Anxiolytics are appropriate if care is taken to avoid hypoventilation and CO2 retention. These patients are more sensitive to the respiratory depressant effects of sedatives and opioids.

Choice of Anesthesia

• Consider regional techniques to avoid airway instrumentation, mechanical ventilation, and systemic opioid administration. • A combination of regional and general anesthesia may assist with early ambulation, decrease in opioid use, and return of respiratory function.

Monitors

• Standard ASA monitors. • Arterial line placement for frequent ABG draws may be considered. A large gradient may exist between the arterial and end-tidal CO2 due to an increase in dead space. PaO2

measurements may aid with ventilator settings.

Induction/Airway Management

• A slow and controlled induction should be performed to allow for attainment of an adequate depth of anesthesia and onset of muscle relaxation prior to airway instrumentation. • Agents – Propofol does not bronchodilate the airways but blunts the laryngeal response. – Ketamine can provide bronchodilation; however, its side effect of increasing secretions is often undesirable. – Volatile agents may be introduced after IV induction to bronchodilate the airways. Alternatively, mask induction may be chosen. – Lidocaine 1–1.5 mg/kg IV or 4% sprayed topically prior to intubation may reduce intraoperative or postoperative coughing. • Avoid hyperventilation while bag masking if the patient is a CO2 retainer.

Maintenance

• The patient should be adequately anesthetized to avoid laryngospasm and bronchospasm. • Nitrous oxide can increase pulmonary artery pressures and is often avoided. • Ventilation – Maximize oxygenation to avoid increases in pulmonary hypertension. – Correct severe hypercapnia without hyperventilating (can result in respiratory alkalosis due to chronic increase). – PEEP may prevent airway closure and improve lung compliance. – I:E ratio should allow sufficient time for expiration and avoid auto-PEEP. • Mucus can be softened with adequate IV fluid maintenance and warm, humidified inspiratory gases.

Extubation/Emergence

• Suction the endotracheal tube prior to extubation. • Consider deep extubation when appropriate. • The use of IV lidocaine prior to extubation may help to suppress airway reflexes.

FOLLOW-UP BED ACUITY

• Vigilance for bronchospasm • Supplemental O2 (nasal cannula, face mask) without suppressing hypercarbic drive

• Thoracic and upper abdominal surgeries are associated with atelectasis, hypoxemia, and slow return to baseline respiratory function. FRC may not return to baseline following these procedures until 2 weeks postoperatively. • Pulmonary care – Chest physiotherapy – Incentive spirometry – CPAP

• Acute respiratory failure • Atelectasis • Bronchospasm • Pneumonia

REFERENCES

1. abe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176:532–555.

2. merican Lung Association Epidemiology and Statistics Unit Research and Program Services Division. Trends in COPD (Chronic Bronchitis and Emphysema): Morbidity and Mortality. February 2010.

3. MacNee W. Pathogenesis of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(4):258–266. 4. Warner DO, Warner MA, Offord KP, et al. Airway obstruction and perioperative complications in smokers undergoing abdominal surgery. Anesthesiology. 1999;90(2):372– 379.

ADDITIONAL READING

• Blanchette CM, Roberts MH, Peterson H, et al. Economic burden of chronic bronchitis in the United States: A retrospective case-control study. Int J Chron Obstruct Pulmon Dis. 2011;6:73–81. • www.aafp.org Management of Chronic Bronchitis • Cor pulmonale • Pulmonary function tests • Cigarette smoking • Pulmonary hypertension • Postoperative pulmonary complications

CODES • 491.9 Unspecified chronic bronchitis • 496 Chronic airway obstruction, not elsewhere classified ICD10 • J42 Unspecified chronic bronchitis • J44.9 Chronic obstructive pulmonary disease, unspecified

CLINICAL PEARLS

• Assess the severity of disease in order to plan appropriate preoperative medications and intraoperative technique, as well as postoperative extubation, level of acuity, and pulmonary rehabilitation.

• Evaluate for respiratory tract infections by noting fever, mucus quality or quantity greater than normal, and increase in SOB. • Baseline O2 saturation and review of home O2 dependence aid in PACU management and discharge plan.

CHRONOTROPY Ramana V. Duvvuri, MD

BASICS DESCRIPTION

• Chronotropy refers to the ability of the heart to change its rate of electrical depolarization, with corresponding mechanical contraction. • Positive chronotropy indicates an increase in heart rate – Generally occurs in response to physiologic stress and is mediated by the autonomic nervous system. – Increases cardiac output directly. – Normal positive chronotropic response decreases in elderly patients. • Negative chronotropy indicates a decrease in heart rate and can be beneficial in clinical situations such as myocardial ischemia, Tetralogy of Fallot, hypertrophic cardiomyopathy and stenotic valves. PHYSIOLOGY PRINCIPLES

• Pacemaker cells exist in different regions of the heart: The sinoatrial (SA) node, the atrioventricular (AV) node, and the His–Purkinje bundle. Each region has its own intrinsic rate of action potential firing. Pacemaker cells in the SA node have the highest intrinsic rate of all regions and thus drive the rest of the conduction system; they are considered to be the “pacemaker” of the heart (1). • Spontaneous depolarization. The SA nodal cells have no true resting potential, but instead generate regular, spontaneous action potentials. • Intracellular Ca2+ modulation leads to diastolic depolarization in the node. The depolarization propagates through the rest of the conduction system and leads to systolic contraction of myocytes (1). • Rate of spontaneous depolarization. Under the control of sympathetic and parasympathetic nerve activity as well as circulating catecholamines. • Muscarinic acetylcholine receptors are densely located in the SA node. When agonized, they hyperpolarize the SA node cell membranes and decrease the spontaneous phase 4 slope, resulting in negative chronotropy. They also function to prolong refractoriness and AV nodal action potential propagation. – Agonism can result from parasympathetic nervous system activity, such as an increase in vagal tone. – Antagonism can result from sympathetic nervous system activity (1).

FIGURE 1. Sympathetic activity results in a hypopolarized (more positive) membrane resting potential and an increased

spontaneous phase 4 slope. Conversely, vagal activity results in a hyperpolarized (more negative) membrane resting potential and a decreased spontaneous phase 4 slope.

• Beta-receptors are located in the SA node; when agonized, they lead to altered intracellular Ca2+ release, via a cAMP pathway, resulting in positive chronotropy (1). – Mostly beta-1 receptors but some role for beta-2 receptors have also been described (1). – Agonism from intrinsic molecules include epinephrine, norepinephrine, and dopamine (2).

ANATOMY

• The SA node is located at the junction of the superior vena cava and the right atrial appendage – It is innervated by fibers from both the sympathetic and parasympathetic (vagal) nervous systems (1).

DISEASE/PATHOPHYSIOLOGY

• Positive chronotropy can be used to – Increase cardiac output (stroke volume times heart rate). Used to treat severe bradycardia (e.g., oculocardiac reflex or vasovagal reflex). – Decrease regurgitant volume in aortic or mitral regurgitation. By decreasing the systolic time, the regurgitant volume also decreases. • Negative chronotropy is a therapeutic modality used in several disease states: – Coronary artery disease/myocardial ischemia. Decreases myocardial oxygen demand (3) as well as supply (increases diastolic time and duration that the left ventricle is perfused). – Acute aortic dissection. Decreased heart rate reduces shear stress on the aorta (4)[A]. – Hypertrophic/obstructive cardiomyopathy. Dynamic outflow obstruction will decrease as the heart has more time to fill and does not empty as much (3). – Stenotic valve lesions (e.g., aortic stenosis and mitral stenosis). Allows for increased ventricular filling (increased diastolic time during each cardiac cycle) along with improved ejection of blood (increased systolic time during each cardiac cycle). • Chronically elevated resting heart rate has multiple negative myocardial and vascular consequences: – Impaired left ventricular (LV) function – Impaired LV relaxation – LV hypertrophy – Endothelial injury/atherosclerosis (3)

Pediatric Considerations

Neonatal left ventricles are stiffer than in adults and are less able to tolerate volume loads.

Because stroke volumes are relatively fixed, they become dependent on the heart rate to maintain cardiac output (5)[A]. Geriatric Considerations

Elderly patients are more prone to chronotropic incompetence—the inability to adequately increase heart rate in response to normal stimuli (<85% maximal predicted heart rate). This may be secondary to remodeling that is associated with an augmentation of collagen content. It has also been hypothesized that it can be a sign of occult coronary artery disease and may correlate with increased mortality (6).

PERIOPERATIVE RELEVANCE

Negative chronotropy is accomplished using

• Beta-receptor antagonists: Metoprolol, propranolol, esmolol, and atenolol. They function to decrease spontaneous depolarization of SA node cells and thus slow the heart rate (7). • Ca2+ channel antagonists (class IV antiarrhythmics): Diltiazem and verapamil (8). They function to block L-type Ca2+ channels found in the SA and AV nodes, thus slowing automaticity as well as AV conduction (9). Positive chronotropy can result from • Sympathomimetics – Endogenous molecules (available for exogenous administration) Norepinephrine stimulates both alpha-1 and beta-1 receptors. Unopposed vasoconstriction from alpha-1 stimulation may cause a reflex bradycardia that is capable of off-setting chronotropic responses from beta-1 stimulation (2). Epinephrine stimulates beta-1, beta-2, and alpha-1 receptors and is a powerful chronotrope, especially at low doses (0.01–0.05 μg/kg/min) (2). Dopamine stimulates D1, beta-1, and alpha-1 receptors; it has a predominant chronotropic beta-1 response at mid-range doses (2–10 μg/kg/min) (2). – Synthetic molecules Isoproterenol is a nonselective beta-1 and beta-2 agonist (2). Dobutamine is a selective beta-1 agonist (2). Ephedrine acts indirectly to increase the release of stored norepinephrine from synaptic junctions as well as directly binds to beta-1 receptors. Ephedrine is less effective when stores of norepinephrine have been depleted from the synaptic junction as in congestive heart failure (2). • Muscarinic acetylcholine antagonists also increase chronotropy by blocking vagal transmission to the SA and AV node. They include atropine and glycopyrrolate. EQUATIONS

Cardiac Output (CO) = Stroke Volume (SV) × Heart Rate (HR)

REFERENCES

1. Lakatta EG. Beyond Bowditch. The convergence of cardiac chronotropy and inotropy. Cell Calcium. 2004;35:629–642.

2. Kee VR. Hemodynamic pharmacology of intravenous vasopressors. Crit Care Nurse. 2003;23:79–82.

3. Liu H, Fox CJ, Zhang S, et al. Cardiovascular pharmacology: An update. Anesthesiol Clin. 2010;28:723–738. 4. Menon V, Sengupta J, Unzek S. Optimal management of acute aortic dissection. Curr Treat Options Cardiovasc Med. 2009;11:146–155.

5. Romero T, Covell J, Friedman WF. A comparison of pressure-volume relations of the fetal, newborn, and adult heart. Am J Physiol. 1972;222(5):1285–1290. 6. Lauer MS, et al. Impaired heart rate response to graded exercise: Prognostic implications of chronotropic incompetence in the Framingham Heart Study. Circulation. 1996;93:1520– 1526. 7. Gorre F, Vandekerckhove H. Beta-blockers: Focus on mechanism of action. Which betablocker, and why? Acta Cardiologica. 2010;65(5):565–570. 8. Reil JC, et al. Heart rate reduction in cardiovascular disease and therapy. Clin Res Cardiol. 2011;100:11–19. 9. Tamargo J, Caballero R, Delpón E. Pharmacological approaches in the treatment of atrial fibrillation. Curr Med Chem. 2004;11:13–28.

ADDITIONAL READING

• Sun LS, Schwarzenberger JC. Cardiac physiology. In: Miller RD, Ericksson LI, Fleisher LA et al., Eds. Miller’s Anesthesia. 7th ed. Philadelphia, PA: Churchill Livingstone, 2009.

See Also (Topic, Algorithm, Electronic Media Element) • cAMP • Pacemaker cells in heart • Thoracic aneurysm repair • Hypertrophic cardiomyopathy • Mitral regurgitation • Mitral stenosis • Tachycardia

CLINICAL PEARLS

• Chronotropy is under the control of the autonomic nervous system; both sympathetic and parasympathetic nerve endings are located at the pacemaker cells of the heart. Additionally, circulating catecholamines can agonize beta- receptors. Positive chronotropy mediated by the body does not typically result in an isolated phenomenon; it is usually in response to an overall sympathetic state that serves to increase inotropy and systemic vascular resistance. • Understanding of this physiology allows the clinician to modulate the heart rate in the perioperative period and with certain disease states.

CILIARY FUNCTION

Thomas Ledowski, MD, PD, DEAA, FANZCA

BASICS DESCRIPTION

• Ciliary function and the integrity of the mucus layer are the two most important determinants of mucociliary clearance (MC). – Toxins, dust, microorganisms, and other debris entrapped in the mucus are removed from the respiratory system by the cephalad stroke of cilia. – In addition to binding various substances and hindering their way further down into the respiratory tract, tracheobronchial mucus also has directly antibacterial as well as immunological functions. • For clinical purposes, ciliary function and mucus integrity need to be treated as one unit that determines MC. PHYSIOLOGY PRINCIPLES

• Cilia – Cilia in the respiratory tract “sweep” mucus cephalad until it can be expectorated. – On the microscopic level, ATPase activity, resulting in adenosine triphosphate (ATP) hydrolysis, provokes conformational changes in the interconnecting dynein arms of ciliary microtubules. ATPase functions as a motor that results in sliding between adjacent microtubules A and B (see Anatomy). – The bending or “stroke” of the cilium is explained by the initial activation of dynein in only half the microtubules, with the activation of the other half accounting for the backwards movement of the cilium (1). This is referred to as the effective stroke or principal bend and the recovery stroke or reverse bend, respectively. – Ciliary beat frequency is 11–15 Hz. • Mucus – Liquid secretion from submucosal glands is largely under neuronal control, where vagal stimulation causes an increase in glandular secretion (via local ACH release). – Substance P and vasoactive intestinal peptide (VIP) are second-line regulatory mechanisms that provoke the upregulation of mucus secretion. – On the cellular level, liquid secretion is largely driven by active Cl− and HCO3− secretion,

creating a lumen-negative potential difference to pull cations through paracellular tight junctions. This results in an osmotic gradient that drives water movement across the epithelial barrier (2). – Mucus contains ∼95% water. – Tracheal mucus clearance is remarkably rapid with a speed of 4–20 mm per minute. Velocities in the peripheral airways are lower.

Geriatric Considerations

• Both ciliary beat frequency and MC are significantly reduced (nearly halved) in elderly patients! • Ultrastructurally, microtubular abnormalities increase with age.

ANATOMY

• Cilia – Cilia are found in the upper (nasal cavities, sinuses, Eustachian tubes, middle ear) and lower (trachea to terminal bronchioles) airway, decreasing in height from 5 to 7 μm (trachea) to 2 to 3 μm (bronchioles). – There are ∼100–200 cilia on each ciliated cell, with ∼3 ×1012 cilia in total. – Underneath the outer cell membrane of each cilium, the ciliary axoneme is composed of over 250 proteins forming a “9 + 2” pattern with 9 peripheral microtubular pairs (A and B) surrounding a central pair (1). – The peripheral A microtubules have an attached inner and outer dynein arm; all pairs are connected via nexin links. – Central and peripheral microtubules are connected via radial spokes to finally form the complex microtubular unit that equals 1 cilium. • Mucus – All ciliated respiratory epithelia are covered by a blanket of viscoelastic mucus that is divided into 2 layers: A deeper, more liquid sol-layer that allows unhindered movement of cilia. A superficial mucous layer to entrap substances. – Submucosal glands consist of Secretory tubules that contain serous and mucous cells. Serous cells have apical vesicles containing lysozyme, lactoferrin, IgA, peroxidases, and albumin (2). Mucous cells produce gel-forming mucins or polysaccharides. A collecting duct A ciliated duct that passes through the smooth muscle and lamina propria of the mucosa and finally opens to the airway surface.

DISEASE/PATHOPHYSIOLOGY

• Reduced MC can result from certain conditions or diseases, artificial or mechanical ventilation, and drugs. – Conditions and diseases Immotile cilia (Kartagener’s) syndrome; the absence of dynein arms or radial spokes can result in impairment, or complete loss, of ciliary function. Asthma results in inflammation and hypersecretion. COPD and bronchiectasis can result in epithelial damage. Cystic fibrosis; dehydrated and thick mucus is produced as a result of abnormalities in Cl − ion transport. Wegener’s granulomatosis Acute respiratory tract infection as a result of cytotoxins Acute illness such as in intensive care unit (ICU) patients. Extremes of temperature Sleep

Immobility Artificial or mechanical ventilation related High fresh gas flow can dry mucus. High airway pressure reduces ciliary beat frequency (3)[C]. Lack of airway humidification can dry mucus. Bronchial suctioning can result in epithelial damage. Tracheal intubation (decreased MC when compared with laryngeal mask airway) (4)[B] Drugs Volatile anesthetic agents (halothane, isoflurane, sevoflurane, desflurane) (5)[B] can potentially inhibit Cl− channels. The MC inhibitory effects of volatile agents last for ∼60–90 minutes after cessation of their administration. Morphine; evidence is conflicting. Remifentanil, when compared to morphine, may lower MC. Pentobarbital has an inhibitory ciliary effect. Temazepam, diazepam Ketamine at clinical doses Atropine; Evidence is conflicting. Furosemide Tobacco Alcohol Increased MC can also result from certain conditions, ventilatory maneuvers, or drugs. Conditions Exercise Change of posture can have a mucus draining effect Ventilation related Positive end-expiratory airway pressure; studies and evidence are mainly from cystic fibrosis patients. Nasal continuous positive airway pressure; likely has only a short-term effect. Air humidification (e.g., by means of HME devices) Drugs Ketamine at supraclinical doses has been seen during in vitro experiments. Anticholinergic drugs; Evidence is conflicting β2-adrenergic agents; evidence is conflicting. Studies have shown that they may stimulate ciliary beat frequency, but also mucus production. The effect on MC especially in diseased lungs is unclear. Methylxanthines Drugs with likely no significant effect on MC Propofol Midazolam Dexmedetomidine Thiopental Fentanyl

PERIOPERATIVE RELEVANCE

MC is of utmost importance for unhindered gas exchange as a result of the

Maintenance of normal pulmonary physiology Prevention of infection Prevention of airway obstruction and atelectasis Preservation of surfactant function The rate of perioperative pulmonary complications can be reduced with simple perioperative measures such as airway humidification or the avoidance of potentially detrimental ventilation patterns (see above). Laryngeal mask airways may result in reduced MC impairment compared to tracheal intubation (4)[B]. Smoking has a negative impact on MC and on pulmonary complications in ICU patients. Smoking cessation does not appear to have immediate effects on MC function. In fact, compared to nonsmokers, mucus production is ∼50% greater in patients who ceased smoking <8 weeks prior to surgery, 25% higher in those who quit >8 weeks prior to surgery and not significantly different to nonsmokers when stopped smoking >6 months prior to surgery.

GRAPHS/FIGURES

See link under “additional reading.”

REFERENCES

1. Stannard W, O’Callaghan C. Ciliary function and the role of cilia in clearance. J Aerosol Med. 2006;19:110–115. 2. Ballard ST, Spadafora D. Fluid secretion by submucosal glands of the tracheobronchial airways. Respir Physiol Neurobiol. 2007;159:271–277. 3. Piccin VS, Calciolari C, Yoshizaki K, et al. Effects of different mechanical ventilation strategies on the mucociliary system. Intensive Care Med. 2011;37:132–140. 4. Keller C, Brimacombe J. Bronchial mucus transport velocity in paralyzed anesthetized patients: A comparison of the laryngeal mask airway and cuffed tracheal tube. Anesth Analg. 1998;86:1280–1282. 5. Ledowski T, Paech MJ, Patel B, et al. Bronchial mucus transport velocity in patients receiving propofol and remifentanil vs. sevoflurane and remifentanil anesthesia. Anesth Analg. 2006;102: 1427–1430.

ADDITIONAL READING

Electron-microscopic pictures and explanation of cilia structure and movement by Gwen V. Childs, PhD, University of Arkansas for Medical Sciences. How do cilia move? http://www.cytochemistry.net/Cell-biology/cilia.htm

See Also (Topic, Algorithm, Electronic Media Element) Smoking

CLINICAL PEARLS

Preservation of MC is important. An easy way to preserve/improve MC is by airway humidification, low-flow anesthesia, and avoidance of high-pressure/high-volume ventilation. Although preoperative cessation of smoking is generally considered beneficial, its impact on MC may not be evident for several weeks. It may actually decrease MC initially; the clinical relevance of this is unclear. In patients prone to airway complications (e.g., cystic fibrosis patients) careful planning of the anesthetic regime and avoidance of substances that hinder MC further may be beneficial. There is no “magic bullet” drug treatment to improve MC in anesthetized patients or patients with preexisting airway disease.

CIRCLE OF WILLIS

Brooke Albright, MD, MAJ, MC

BASICS DESCRIPTION

The circle of Willis (coW) connects the cerebral blood flow (CBF) from the internal carotid arteries (ICAs) (80% of CBF) with the vertebrobasilar system (VBS) (20% of CBF) in a ring of vessels beneath the hypothalamus. PHYSIOLOGY PRINCIPLES

The circular arrangement of the cerebral arteries creates a collateral system of blood flow that protects the brain from ischemia when one part of the circle becomes blocked or narrowed. ANATOMY

• The coW consists of the following arteries (see Figure 1): – Anterior communicating artery – Paired anterior cerebral arteries – Paired ICAs – Paired posterior communicating arteries (PCOM) – Paired posterior cerebral arteries (PCA)

FIGURE 1. Circle of Willis Anatomy (1)

• The basilar artery along with the two vertebral arteries are referred to as the vertebrobasilar system. It supplies blood to the coW. • The cerebral circulation can be divided into anterior and posterior vessels: – The anterior circulation is supplied by the ICAs (arising from the common carotid arteries). The first branch is the ophthalmic artery, followed by the PCOM, and then the anterior choroidal artery. The ICAs terminate into the anterior and middle cerebral arteries. – The posterior circulation is supplied by the VBS. The vertebral arteries (arising from the subclavian arteries) supply circulation to the spinal cord and give off branches to the cerebrum, midbrain, pons, medulla, and cerebellum. Branches of the vertebral arteries include the anterior spinal artery, paired posterior spinal arteries, and the posterior inferior cerebellar artery. The vertebral arteries then unite to form the basilar artery. The basilar artery terminates by dividing into paired PCA that supply the medial temporal lobe, occipital lobe, and parts of the thalamus.

• The anatomy of the coW is highly variable in adults. These variations are largely the result of fetal development in utero. As early as seven weeks postconception, a preliminary form of the coW is present with approximately equal diameters of all vessels. As the fetus grows so do the components of the coW, eventually assuming the adult morphology (2). The main differences between the fetal and adult coW anatomy are the diameters of the PCOM and the circular part of the PCA. The coW is complete in only 42.1–47% of individuals (3). • It is possible that in some individuals a fetal-type PCA (one supplied primarily by the ICA rather than the vertebral artery) will persist. ICA volume flow is significantly increased and basilar artery flow significantly decreased. In those with absent A1 segments of the anterior cerebral artery, flow between the ICAs is largely asymmetrical (6).

DISEASE/PATHOPHYSIOLOGY

• Approximately 95% of all aneurysms can be found near the coW. • Cerebral aneurysms are classified by size, shape, and location. Size is considered to be one of the most important determinants of future rupture. The ISUIA trial (a large international prospective study) evaluated 5-year cumulative cerebral aneurysm rupture risk based on location and size (4). – Size (anterior/posterior%): <7 mm (0/2.5%) 7–12 mm (2.6/14.5%) 13–24 mm (14.5/18.4%) – Shape: Saccular (most common): The aneurysm has an outpouching. Berry: A saccular aneurysm with a stem or neck. Fusiform: Without an outpouching or stem. • Location: – 85% are located in the anterior circulation Anterior communicating artery (most common site of rupture in anterior circulation) Anterior cerebral arteries Bifurcation of the ICAs Middle cerebral arteries PCOM – 15% are located in the posterior circulation PCA Basilar artery bifurcation • Ischemia, thrombosis, or hemorrhage of a cerebral artery is known as a cerebrovascular accident (CVA). It is defined as a new focal or global neurological (motor or sensory) deficit lasting >48 hours. – A transient ischemic attack (TIA) is characterized by a sudden vascular-related focal neurologic deficit that resolves within 24 hours. – Occlusion of a specific major intracranial artery will result in predictable clinical neurologic deficits. – Isolated infarction of the anterior cerebral artery is uncommon. – Carotid stenosis can lead to TIAs and CVAs if collateral CBF is not adequate. • Subclavian steal syndrome is a phenomenon of transient cerebral ischemic attacks following

ipsilateral arm exercise in the presence of severe stenosis (>80%) or occlusion of the subclavian artery proximal to the origin of the vertebral artery. It is a flow-related phenomenon. – At rest, the arm becomes dependent on the collateral vessels from the head, shoulder, and neck. – During exercise, blood flows retrograde from the ipsilateral vertebral artery to the distal subclavian artery to supply the arm. In doing so, blood is diverted from the circle of Willis and can result in transient cerebral ischemia. • Arteriovenous malformation (AVM) is an abnormal connection between arteries and veins; whereby high-pressure arteries connect directly to low-pressure veins without passing through a capillary network. They are most often congenital lesions that can be found anywhere in the body. They are usually asymptomatic. In rare circumstances, cerebral lesions may bleed or expand, leading to CNS symptoms. The most common symptoms of cerebral AVMs are seizures, headache, and pain. • Moyamoya syndrome is a disease in which the lumen of certain cerebral arteries (mainly the ICAs up to the middle and anterior cerebral arteries) overgrow inwardly to the point of constriction or blockage. This leads to angiogenesis of collateral blood vessels to compensate for lack of blood flow in the region. The collateral network of small blood vessels has the appearance of a “puff of smoke” or “moyamoya,” in Japanese. Problems may arise when these small fragile networks hemorrhage, aneurysm, or clot off.

PERIOPERATIVE RELEVANCE

• Cerebral vasculature imaging (i.e., angiography, MagneticResonance Angiogram (MRA) and Computed Tomography Angiography (CTA)) may be utilized preoperatively or intraoperatively to demonstrate vascular occlusions or emboli at vessel bifurcations after an acute CVA, as well as to diagnose and treat aneurysms. • It may be vitally important to evaluate the cerebral circulation prior to certain surgeries via angiography. For example, in endovascular stent-graft repair for thoracic aortic disease, it is commonly necessary to extend the stent-graft beyond the left subclavian artery (LSA). If the contralateral vertebral artery is hypoplastic and the coW is incomplete or when the left vertebral artery significantly participates in the supply of the superior portion of the anterior spinal artery, then coverage of the LSA may disrupt collateral pathways to the posterior cerebral circulation and spinal cord; this results in serious neurological complications. In order to avoid such debilitating complications, careful imaging of the right vertebral artery up to the basilar artery may be mandatory preoperatively (7). – In certain situations, neurologic complications can be minimized when a prophylactic carotid subclavian bypass is performed, as well as avoidance of intraoperative hypotension (8). • During carotid endarterectomy (CEA) surgery, an incomplete coW formation predisposes approximately one-sixth of individuals to cerebral ischemia during carotid clamping or transient closure of the carotid artery. In those with coexisting contralateral ICA occlusion, the risk of cerebral ischemia rises more than threefold (9). – Some institutions utilize preoperative angiography of the cerebral vasculature to assess collateral flow and determine the possible need for intra-luminal shunting during the procedure.

• Middle cerebral artery blood flow velocities can be measured in real-time by transcranial Doppler (TCD) to detect and quantify embolic signals intraoperatively or at the bedside. It can be beneficial in situations such as patients status post-CEA and/or patients undergoing thrombolytic therapy. – TCD predictors of stroke after CEA include emboli during wound closure, >90% decrease in middle cerebral artery peak systolic velocity at cross-clamping, and >100% increase of the pulsatility index of the Doppler signal at clamp release (10).

REFERENCES

1. Illustration by Brooke Albright, MD.

2. ucchiara B, Detre J. Migraine and circle of Willis anomalies. Medical Hypotheses. 2008;70:860–865.

3. Ardakani SK, Dadmehr M, Nejat F, et al. The cerebral arterial circle (circulus arteriosus cerebri): An anatomical study in fetus and infant samples. Pediatr Neurosurg. 2008;44:388–392. 4. eibers DO, Whisnant JP, Huston J 3rd. Unruptured intracranial aneurysms: Natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet. 2003;362:103– 110. 5. Lall RR, Eddleman CS, Bendok BR, et al. Unruptured intracranial aneurysms and the assessment of rupture risk based on anatomical and morphological factors: Sifting through the sands of data. J Neurosurg FOCUS. 2009;26(5):E2. 6. endrikse J, van Raamt AF, van der Graaf Y, et al. Distribution of cerebral blood flow in the circle of Willis. Radiology. 2005;235:184–189. 7. Manninen H, Tulla H, Vanninen R, et al. Endangered cerebral blood supply after closure of left subclavian artery: Postmortem and clinical imaging studies. Ann Thorac Surg. 2008;85:12–16. 8. Feezor RJ, Martin TD, Hess PJ, et al. Risk factors for perioperative stroke during thoracic endovascular aortic repairs (TEVAR). J Endovasc Ther. 2007;14(4):568–573. 9. Manninen H, Mkinen K, Vanninen R, et al. How often does an incomplete circle of Willis predispose to cerebral ischemia during closure of carotid artery? Postmortem and clinical imaging studies. Acta Neurochir. 2009;151:1099–1105. 10. Ackerstaff RG, Moons KG, va de Vlasakker CJ, et al. Association of intraoperative transcranial Doppler monitoring variables with stroke from carotid endarterectomy. Stroke. 2000;31(8):1817. See Also (Topic, Algorithm, Electronic Media Element) • Carotid endarterectomy surgery • Cerebral aneurysms • Arteriovenous malformations • Transient ischemic attacks • Subclavian steal syndrome

CLINICAL PEARLS

• The coW is complete in only 42.1–47% of the population. An incomplete coW significantly predisposes individuals to cerebral ischemia during certain procedures such as CEA and TEVAR. • Some institutions are beginning to utilize preoperative cerebral vasculature angiograms to guide surgical intervention and predict the need for additional cerebral protection and/or monitoring. • Although the majority of aneurysms develop in the anterior circulation, current literature suggests higher risks of rupture are associated with posterior circulation aneurysms with size >7 mm (5)[A].

CIRCULATORY ARREST January Y. Tsai, MD

BASICS DESCRIPTION

• Cessation of the systemic circulation is either – Unintentional: Due to cardiac arrhythmia or arrest, ischemia, electrolyte abnormality, or extreme hypothermia. – Therapeutic (planned or emergent): Hypothermic circulatory arrest temporarily suspends blood flow under very cold body temperatures to allow for a motionless and bloodless surgical field for intracardiac and aortic procedures. This requires increased coordination among the anesthesiologist, surgeon, and perfusionist. • At cold temperatures, cellular activity levels slow significantly and allow blood circulation to be suspended for up to 40 minutes without neurological harm to the patient. • Additionally, adjunctive selective cerebral perfusion (antegrade or retrograde) is commonly used now, whereas previous deep hypothermic circulatory arrest (DHCA) relied on hypothermia alone for neuroprotection. PHYSIOLOGY PRINCIPLES

• Unintentional: High/normal cerebral metabolic rate of oxygenation (CMRO2) during periods

of limited or no cerebral perfusion may rapidly lead to irreversible hypoxic brain injury. • Therapeutic: CMRO2 decreases 7%/°C. At 23°C, the CMRO2 theoretically approaches zero.

Types of cerebral perfusion include retrograde and antegrade. • Retrograde cerebral perfusion (RCP) – Cannulation is via the superior vena cava (SVC). – Perfusion with cold blood – Perfusion theoretically occurs via the SVC to the internal jugular (IJ) vein to the sigmoid sinuses to the venules to the capillaries to the arterioles to the circle of Willis (coW) to the internal carotid artery (ICA) to the right and left common carotid arteries (RCC/LCC) and then to the aortic arch. – Conventional maximum flow rate of 500 mL/min in the circuit is utilized to maintain the SVC catheter pressure <25 mm Hg. – Advantages More homogenous brain cooling Washout of air bubbles, embolic debris, and metabolic waste products Prevention of cerebral blood cell microaggregates Delivery of O2 and metabolic substrates – Potential disadvantages Excessive RCP pressure has been related to the potential for increased cerebral edema leading to neurologic injury (1).

Increased intracranial pressure and cerebral edema may occur due to direct perfusion of hypothermically vasoconstricted microvasculature and tissues. Impeded venous return may also exacerbate intracranial pressure and edema. Low levels of substrate Duration before cerebral consequences: 45 minutes • Anterograde cerebral perfusion – The right axillary artery is either directly cannulated or a graft is inserted. – Perfusion with cold blood – Once antegrade perfusion is initiated, the brachiocephalic artery is clamped, and blood flow proceeds from the right axillary artery to the right subclavian artery to the brachiocephalic artery (very short segment) to the RCC and then to the brain. – Mean perfusion pressure usually 40–70 mm Hg. – Cerebral oximetry may be used to evaluate changes in regional brain perfusion. If leftsided cerebral perfusion decreases, direct visual cannulation of the left carotid artery and perfusion with cold blood may be performed to enhance flow. – Advantages Uninterrupted supply of nutrients to the brain Prolonged duration of safe circulatory arrest compared to RCP – Potential disadvantages Air or plaque emboli due to manipulation of frequently atheromatous great vessels and direct antegrade flow to the cerebral circulation. Unilateral flow requires an intact coW, which is present in only ∼30% of the population. The most common absences include a lack of the P1 segment of the posterior cerebral artery (PCA), posterior communicating artery (PComm), or A1 segment of the anterior cerebral artery (ACA). Prior ischemic stroke in any of these territories may also result in an incomplete circle (2). Axillary cannula or graft insertion can increase the complexity of surgery. A greater number of cannulae are present on the surgical field. Duration before cerebral consequences: 60 minutes. • Controversial topics – Optimal lowest temperature is unknown. While hypothermia decreases the CMRO2

(provides neuroprotection), it can adversely affect coagulation and microvascular perfusion; profound hypothermia (∼14°C) may have more profound adverse effects. In addition, lower temperature is associated with longer cardiopulmonary bypass (CPB) times due to longer rewarming times (longer CPB time is associated with poorer outcomes). With the advent of antegrade cerebral perfusion, the duration of circulatory arrest may be prolonged, and decreased levels of hypothermia may be utilized (up to 25°C) (3). – Optimal flow rate and pressure are unknown. Both flow and perfusion pressure should meet tissue metabolic requirements without causing tissue injury. Although conventional values have been established, whether they should be adjusted for temperature-related differences in vascular tone is not known. – Barbiturates or propofol may be used for neuroprotection in conjunction with EEG monitoring. Isoelectric EEG implies decreased CMRO2 and improved cerebral protection.

However, studies have shown that patients receiving thiopental required more inotropic support, but significant neuroprotection was not provided (4). – Steroids (large-dose methylprednisolone 30 mg/kg) are also commonly used for neuroprotection, but experimental results are mixed. For example, one animal study found that systemic pretreatment fails to attenuate neuronal cell injury after prolonged DHCA and that the steroid group showed increased neuronal apoptosis in the dentate gyrus (5). However, another study found improved global and regional cerebral blood flow (CBF) and CMRO2 with steroid use (6). ANATOMY

Therapeutic circulatory arrest is used for large or difficult to access cerebral aneurysms and aortic repair in order to create a motionless, bloodless field. Continuous circulation during open exposure of the aortic arch or cerebral circulation would create a difficult surgical field or massive hemorrhage. PHYSIOLOGY/PATHOPHYSIOLOGY

Brachiocephalic artery repair. Loss of the left radial arterial line waveform can occur during left-sided repair. PERIOPERATIVE RELEVANCE

• Inadequate cardioprotection – Cardiac ischemia may occur due to inadequate cardioplegia administration or inability to terminate electrical activity during circulatory arrest. – Inability to wean from CPB may be secondary to myocardial stunning. – Ventricular fibrillation may occur during rewarming. Arrhythmias may also occur postoperatively. • Hypothermia – Hemoconcentration with hypothermia and increased blood viscosity may decrease microvascular perfusion. – Consider isovolemic hemodilution • Coagulopathy – Temperatures required for protection are outside the normal range of coagulation enzymes. – Increased bleeding after termination of CPB and protamine administration – Consider antifibrinolytics, DDAVP, autologous blood transfusion, early plasma, and factor administration based on clinical evaluation or coagulation panels. • Postoperative shivering – Increased metabolic rate – Increased O2 consumption

• Cerebral injury is a major cause of morbidity and mortality following aortic arch surgery. – Stroke due to insufficient neuroprotection may occur early (temporary neurological dysfunction) or late (permanent neurological dysfunction) due to cerebral hypoperfusion or atheromatous emboli. It may be due to ischemia reperfusion injury or rewarming injury.

– Spinal cord ischemia due to prolonged arrest of vertebral artery flow. Neuromonitoring techniques may be used to detect changes. • Inadequate lower body organ protection – Renal insufficiency – Hepatic ischemia • Decreased metabolic rate – Metabolism of most drugs is decreased while hypothermic. – Muscle relaxation may outlast sedation postoperatively, especially if redosed. • General end-organ effects – Endothelial dysfunction – Apoptosis – Necrosis • Stress response and hyperglycemia – May be refractory to insulin during circulatory arrest and then increasingly sensitive with rewarming. – Aggressive, tight treatment is usually not warranted.

REFERENCES

1. Estrera A, Garami Z, Miller C, et al. Determination of cerebral blood flow dynamics during retrograde cerebral perfusion using power M-mode transcranial Doppler. Ann Thorac Surg. 2003;76:704–710. 2. reasy J. Dating Neurologic Injury. Springer 2011:12. 3. Salazar J, Coleman R, Griffith S, et al. Brain preservation with selective cerebral perfusion for operations requiring circulatory arrest: Protection at 25°C is similar to 18°C with shorter operating times. Eur J Cardiothoracic Surg. 2009;36(3):524–531. 4. Zaidan J, Klochany A, Martin W, et al. Effect of thiopental on neurologic outcome following coronary artery bypass grafting. Anesthesiology. 1991;74:406–411. 5. Schubert S, Stoltenburg-Didinger G, Wehsack A, et al. Methylprednosolone fails to attenuate neuronal injury after deep hypothermic circulatory arrest in a neonatal piglet model. A&A. 2005; 101(5):1311–1318. 6. Langley S, Chai P, Jaggers J, et al. Preoperative high dose methylprednisolone attenuates the cerebral response to deep hypothermia circulatory arrest. Eur J Cardiothoracic Surg. 2000;17:279–286.

ADDITIONAL READING

• Apostolakis E, Koletsis EN, Dedeilias P, et al. Antegrade versus retrograde cerebral perfusion in relation to postoperative complications following aortic arch surgery for acute aortic dissection type A. J Card Surg. 2008;23(5):480–487.

See Also (Topic, Algorithm, Electronic Media Element) • Cardiopulmonary bypass • Neuroprotection

• Thoracic aneurysm repair • Craniotomy, cerebral aneurysm clipping • Hypothermia

CODES ICD9

427.5 Cardiac arrest ICD10

I46.9 Cardiac arrest, cause unspecified

CLINICAL PEARLS

• Use NIRS and/or EEG to monitor cerebral activity. • May need both radial and femoral arterial lines for monitoring. • Ventricular fibrillation is likely during cooling and rewarming. Consider lidocaine, magnesium, esmolol, and amiodarone to decrease the incidence; be prepared to defibrillate. Pacing may be required. • Steroids are possibly beneficial for cerebral edema. • Coagulopathy may require early and aggressive monitoring and blood product transfusion. Order products early if necessary and have sufficient venous access. • Redistribution of temperature postoperatively may cause significant hypothermia, which may require aggressive rewarming.

CIRRHOSIS

Phoebe Lee, MD Andrea Vanucci, MD, DEAA

BASICS DESCRIPTION

• Cirrhosis is the common histological outcome of chronic liver disease resulting in cell necrosis and altered liver structure and function. It is characterized by – Fibrosis – Regenerative nodules of hepatic cells – Impaired metabolic and synthetic function – Increased hepatic resistance to blood flow • Portal hypertension is the hallmark of decompensated cirrhosis, recognizable by ascites formation, venous collateral development, and episodes of hepatic encephalopathy. EPIDEMIOLOGY Prevalence

Difficult to quantify and regionally dependent on the presence of different risk factors Prevalence

True prevalence of cirrhosis is unknown, as many compensated cases are undiagnosed. Morbidity

• In 2002: Cirrhosis caused 421,000 hospitalizations in the US. • In 2005: 112,000 discharges with chronic liver disease or cirrhosis as the first-listed diagnosis in the US. • Cirrhotic patients are at risk of developing hepatocellular carcinoma (10–25% of cases).

Mortality

• Deaths per 100,000 population: 9.7 • 12th leading cause of death in the US in 2007 (1.2% of all deaths)

ETIOLOGY/RISK FACTORS

Hepatitis C 26%; alcohol related 21%; hepatitis C plus alcohol 15%; hepatitis B 15%; cryptogenic causes 18% (70% are nonalcoholic fatty liver disease [NAFLD], an increasingly recognized cause of cirrhosis); miscellaneous 5% (autoimmune hepatitis, cholestatic liver diseases, cholangitis, hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, druginduced, right-sided heart failure, Budd–Chiari) PHYSIOLOGY/PATHOPHYSIOLOGY

• Impaired metabolic and synthetic function

– Albumin. Important for maintaining oncotic pressure in capillaries; affects drug distribution and elimination by its binding. – Coagulation factors. Vitamin K-derived factors (II, VII, IX, X), protein C, protein S, and antithrombin. – Cytochrome P450 enzymes. Decreased drug metabolism. • Portal hypertension results from impaired hepatic vascular resistance together with increased mesenteric blood flow. This may lead to – Ascites. Describes the accumulation of fluid in the peritoneal cavity. Pathogenesis is controversial and probably different at various phases of the disease. Portal hypertension, splanchnic vasodilation, hypoalbuminemia, and increased levels of sodium retentive hormones contribute to capillary leakage. – Venous collateral development. Results in esophageal varices and acute bleeding as well as hypersplenism with associated leukopenia and/or thrombocytopenia. – Hepatic encephalopathy. Results from elevated circulating neurotoxic gut toxins (due to portocaval shunting and decreased hepatic metabolism). Patients present with depressed levels of consciousness, personality changes, and intellectual impairment.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintain perfusion and oxygenation of the liver to minimize postoperative deterioration of liver function. • Altered pharmacology can result in sensitivity to sedatives, hepatic encephalopathy, and impaired pulmonary or cardiovascular function. Additionally, altered pharmacokinetics includes an increased volume of distribution (Vd), impaired cytochrome P450, and hypoalbuminemia. • Perioperative mortality is severely increased in cirrhotic patients.

PREOPERATIVE ASSESSMENT SYMPTOMS

Fatigue, nausea, decreased appetite, itching, right upper quadrant pain, abdominal distension, jaundice, dark urine, light stools, and easy bruising. History

Prior blood transfusions, tattoos, illicit drug use, alcohol intake, sexual history, exposure to needle sticks, history of jaundice, and family history of liver disease. Signs/Physical Exam

Icterus, palmar erythema, spider telangiectasia, gynecomastia, caput medusae, hepatosplenomegaly, abdominal distension and umbilical hernia from ascites, lower extremity edema, temporal wasting, loss of muscle mass, abnormal mental status, and asterixis. TREATMENT HISTORY

• Medical management depends on the etiology of initial liver disease. Antiviral treatment for hepatitis B and C, abstinence from alcohol, steroids and azathioprine for autoimmune

hepatitis. • Transjugular intrahepatic portosystemic shunts (TIPS) and large volume paracentesis are considered in medically refractory ascites. • Endoscopic variceal ligation and octreotide infusion for acute bleeding.

MEDICATIONS

• Ascites: Sodium restriction (first line), diuretics (second line). • Spontaneous bacterial peritonitis: Cephalosporins usually indicated. • Hepatic encephalopathy: Lactulose and poorly absorbable antibiotics like rifaximin, neomycin, and metronidazole. • Hepatorenal syndrome: Splanchnic vasoconstrictors (midodrine, octreotide) and volume expansion with albumin.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Complete Blood Count (CBC), Complete Metabolic Panel (CMP), Prothrombin Time (PT), International Normalized Ratio (INR), Right Upper Quadrant (RUQ), Ejection Fraction (EF), Model for End Stage Liver Disease (MELD) • RUQ abdominal ultrasound with Doppler to evaluate parenchyma and portal venous blood flow • Abdominal CT or MRI to evaluate parenchyma (hepatocarcinoma) and vasculature

CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular (1)[A] – Hyperdynamic circulation: Decreased systemic vascular resistances, arterial BP, and increased heart rate lead to a high cardiac output (HCO) status. Increased CO is unequally distributed with a preferential flow toward the visceral compartment. Peripheral arteries may be dilated or constricted in advanced disease. – Autonomic dysregulation with blunted sympathetic and parasympathetic responses. – Cirrhotic cardiomyopathy: Impaired cardiac contractility, systolic and diastolic dysfunction, and ECG abnormalities (e.g., prolonged QT) may lead to ventricular arrhythmias and sudden cardiac death. Typically improves after liver transplantation. – Diagnostic tools include a 12 lead ECG (QTc, QT dispersion); resting or stress ECG (EF, volumes, fractional shortening, wall motion, E/A ratio); exercise ECG (exercise capacity, oxygen consumption, pressure × heart rate product). • Hepatorenal syndrome (2)[A] – Acute or subacute renal failure in advanced cirrhosis is caused by vasoconstriction of renal arteries and is characterized by oliguria/anuria and a creatinine >1.5 mg/dL. Kidneys show only minimal histological changes. – Type 1: Rapid course in <2 weeks mandates dialysis and liver transplantation. – Type 2: Slowly progressing course, usually responds to volume expansion. • Hepatopulmonary syndrome – Seen in advanced cirrhosis – Hypoxemia results from pulmonary vasodilation that causes ventilation/perfusion mismatching and intrapulmonary shunting.

– Clinical findings include platypnea and orthodeoxia. – Diagnosis is via contrast ECG with the presence of bubbles in the left atrium four or more beats after the appearance in the right atrium. – Portopulmonary hypertension is the coexistence of portal and pulmonary hypertension. Mean survival is 15 months in the absence of a liver transplant. • Hemostasis (3)[A] – Hemostatic balance is unstable and can tip either way with bleeding or thrombosis. – Hypocoagulability and bleeding tendencies are due to the decreased liver synthesis of coagulation factors and thrombocytopenia. – Hypercoagulability can also be present as suggested by frequent portal vein thrombosis. – Cirrhosis “rebalanced hemostasis” can result from decreased synthesis of anticoagulants like antithrombin III, Protein C and S; may result in normal thrombin generation in vivo. – Traditional coagulation tests such as PT, PTT, and platelet count do not accurately reflect the state of hemostasis. – Prophylactic correction of abnormal laboratory tests to prevent intraoperative bleeding does not have scientific evidence.

Circumstances to delay/Conditions

• Acute hepatitis (transaminases >10 times normal values) (4)[A] • Child–Pugh type C • MELD score >14

CLASSIFICATIONS

• Child–Turcotte–Pugh (CTP) and MELD classification systems were initially used for predicting mortality after portocaval shunt/TIPS placement. They are now used to predict surgical risk in patients with liver disease (4)[A]. – Child’s A (5–6 points): Postoperative mortality 10%; Child’s B (7–9 points): Postoperative mortality 31%; Child’s C (10–15 points): Postoperative mortality 76%. • MELD score: Complex logarithmic formula incorporating, bilirubin, INR, and serum creatinine (scale 6–40). – Score <8: Postoperative mortality 5.7%; Score >20: Postoperative mortality >50%

TREATMENT PREOPERATIVE PREPARATION Premedications

Judicious use of sedatives; may have prolonged central nervous system depression, and trigger/worsen hepatic encephalopathy. Special Concerns for Informed Consent

• Abnormal mental status may preclude giving a valid medical consent. • Potential for blood or plasma transfusion.

INTRAOPERATIVE CARE

Choice of Anesthesia

• Depends on the procedure • Regional anesthesia: Usual cautions and contraindications apply. Epidural hematomas are of greatest concern from the coagulopathy associated with liver surgery, especially in cirrhotic patients.

Monitors

• Dependent on surgery. High-risk or prolonged procedure should have a low threshold for invasive monitors (arterial lines, central lines, “less invasive” cardiac output monitors). • Thromboelastogram may help clinicians to distinguish between medical versus surgical bleeding and guide the transfusion of blood products.

Induction/Airway Management

• Induction may be associated with profound hypotension. Patients are often intravascularly volume depleted, but with total body volume overload. • Atracurium or cisatracurium are preferred muscle relaxants (metabolism is independent of the liver or kidney). Other muscle relaxants may be acceptable but can have prolonged duration. • Rapid sequence induction should be considered in patients with ascites or gastrointestinal bleeding. • Patients with ascites causing respiratory impairment (tachypnea, use of accessory muscles, hypoxia on pulse oximetry, or arterial blood gas) may require peritoneal drainage and albumin replacement prior to anesthesia induction.

Maintenance

• Isoflurane, sevoflurane, and desflurane have limited liver metabolism and minimal impairment of hepatic arterial blood flow. • Halothane should be avoided; associated with mild hepatic dysfunction and severe immunemediated hepatitis. • All opiates, except remifentanil, are metabolized by the liver, and should be used judiciously.

Extubation/Emergence

• Standard extubation criteria • Slower emergence and return of neuromuscular function may result from a reduced ability to clear medications. • Patients at risk for aspiration should be wide awake prior to extubation; patients who have an altered level of consciousness may warrant postoperative intubation.

FOLLOW-UP BED ACUITY

Admission to an intensive care unit (ICU) may be indicated to monitor and support circulatory and respiratory function after intermediate/high risk procedure.

MEDICATIONS/LAB STUDIES/CONSULTS

Hepatology and hematology consultation may be considered for management of coagulopathy. COMPLICATIONS

• Postoperative liver failure • Hemostatic derangements • Postoperative delirium • Pulmonary edema • Pleural effusion

REFERENCES

1. Moller S, Henriksen JH. Cardiovascular complications of cirrhosis. Gut. 2008;57:268–278. 2. Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009;361:1279–1290. 3. Lisman T, Caldwell SH, Porte RJ, et al. Hemostasis and thrombosis in patients with liver disease: The ups and downs. J Hepatology. 2010;53(2):362–371. 4. Malik SM, Ahmad J. Preoperative risk assessment for patients with liver disease. Med Clin North Am. 2009;93:917–929. See Also (Topic, Algorithm, Electronic Media Element) • Liver transplant • Thromboelastogram

CODES ICD9 • 571.2 Alcoholic cirrhosis of liver • 571.5 Cirrhosis of liver without mention of alcohol ICD10 • K70.30 Alcoholic cirrhosis of liver without ascites • K74.60 Unspecified cirrhosis of liver

CLINICAL PEARLS

• Assess perioperative risk with CPT/MELD scores. • Optimize liver perfusion and oxygenation; may require invasive monitoring. • Altered pharmacokinetics of drugs requires cautious titration to effect; consider adjusting bolus doses and frequency as appropriate. • Consider admitting cirrhotic patients to an ICU after intermediate/high risk surgery.

CLEFT PALATE AND LIP REPAIR Ranu Jain, MD

BASICS DESCRIPTION General

• Cleft palate, along with cleft lip, is among the most common congenital malformations. It is defined as a defect in palatal growth in the first trimester and can be associated with various other syndromes. • Cleft palate is classified and described as follows: – Primary: Anterior to the incisive foramen. Includes lip and alveolus – Secondary: Posterior to the incisive foramen. Includes hard palate, soft palate, and the uvula. Submucous clefts can occur. – Midline (most common), unilateral, or bilateral – Complete or incomplete. Depends on whether or not the cleft involves the entire anatomic structure. – Occurring with cleft lip (75%) – Cleft lip occurring without cleft palate; when this occurs, it is unilateral 80% of the time and bilateral 20% of the time. • Closure of the soft palate is recommended at 3–6 months of age, and the hard palate around 12–15 months of age. This allows for growth of the soft palate, which is important for speech development and periosteal maturation. As a result the palate is repaired before speech evolvement. – Pharyngoplasty or pharyngeal flaps may be required for the treatment of velopharyngeal incompetence (incomplete contact between the soft palate and posterior pharynx required for normal speech and swallowing) secondary to anatomic or neurologic dysfunction. This is done during the toddler years or later. – Palatal revision and alveolar bone grafts occur at about 10 years of age. – Rhinoplasty and maxillary osteotomy to complete repair may take place at 17–20 years of age. • Etiology is believed to be multifactorial – Genetic – Drugs – Viruses – Toxins – Associated with other syndromes – Associated with birth defects: Umbilical hernia, clubfoot, limb, and ear abnormalities. Position

• Supine, with a shoulder roll. Alternatively the Rose position may be utilized (supine with head over the operating table edge)

• Table rotated 90–180°

Incision

Edges of the cleft palate Approximate Time 2–4 hours

EBL Expected

Approximately 50 mL Hospital Stay

Overnight stay

Special Equipment for Surgery • Dingman mouth gag • Oropharyngeal pack

EPIDEMIOLOGY Prevalence

• Cleft lip and palate, together, comprise approximately 1:700 births worldwide. • Cleft palate alone is approximately 1:2500 births.

Prevalence

• More common in males than females • Siblings and offspring of patients with cleft lip or palate are at greater risk.

Morbidity

• Recurrent ear infection with effusion is reported in 90% of children with cleft palate. It is due to abnormal compliance and insufficient ventilation of the Eustachian tubes. • If the cleft palate is associated with cleft lip, the defect may expose the nasal cavity to the oral cavity, resulting in swallowing difficulties and failure to thrive, repeated aspiration, and pulmonary infection. • Other secondary defects like abnormal dental development, growth of ala nasi, and velopharyngeal function can also occur. • Associated with more than 300 syndromes

Mortality

Associated with the surgery: <0.5%

ANESTHETIC GOALS/GUIDING PRINCIPLES

• There is a potential for a difficult airway, especially in patients with syndromes. • Narcotics should be administered judiciously to avoid respiratory depression and allow for an awake extubation at the end of the case. Use of regional anesthesia as an adjunct to pain management can be considered.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Failure to thrive • Feeding problems • Fever may suggest acute infection (ear, pulmonary)

History

• Cleft palate is usually diagnosed in utero, or at birth • Flow of milk through nasal passages during feeding • Recurrent ear infections • History of aspiration pneumonia

Signs/Physical Exam

• Unilateral or bilateral • Ranges from a small notch in the lip or can extend from the lip through the upper gum and palate into the bottom of the nose. • Misaligned teeth • Change in nose shape; amount of distortion varies

MEDICATIONS

• Antibiotics for ear infection • Treatment – Before surgery, the goal is to minimize the chance of aspiration and pulmonary compromise. Infants are fed in the upright position with either a preemie or infant nipple. The Haberman nipple is more successful in these patients since they do not have to generate suction to get fluid from the nipple. – In patients with repeated episodes of aspiration, feeding may be performed via a nasogastric tube. – Bilateral myringotomies with ear tube placement may be placed for recurrent ear infections.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Diagnosis of cleft palate occurs during examination after birth, whereas the diagnosis of cleft lip takes place in utero by ultrasound at 18–20 weeks postconception. • Swallow studies to rule out aspiration • Cardiac workup in syndromic patients

CONCOMITANT ORGAN DYSFUNCTION

• Associated anomalies occur 30 times more frequently in patients with isolated cleft palate than in the noncleft population – Umbilical hernia – Clubfoot

– Limb abnormalities – Middle ear abnormalities • Syndromes with associated cleft palate and lip – Pierre Robin syndrome – Fetal alcohol syndrome – Goldenhar syndrome – Treacher Collins syndrome – Nager syndrome – Down syndrome

TREATMENT PREOPERATIVE PREPARATION Premedications

Since the surgery is done around 6 months of age, the child may begin to have stranger anxiety. Consider premedicating with oral midazolam. Special Concerns for Informed Consent

• If associated with other syndromes, parents should be informed about the possibility of difficult intubation and need for postoperative intubation. • Blocks for postoperative pain control.

Antibiotics/Common Organisms

Antibiotic prophylaxis may be needed if cardiac abnormalities are present INTRAOPERATIVE CARE Choice of Anesthesia

General endotracheal anesthesia Monitors

• Standard ASA monitors • Skin/axillary/rectal temperature probes may be used instead of oral/nasal probe. • Additional invasive monitoring may be needed, depending on comorbidities.

Induction/Airway Management

• Induction can be performed with an inhalational or IV technique (if an IV is in place). • Airway obstruction can result in infants with a hypoplastic mandible and wide cleft palate; the tongue can prolapse into the nasopharynx. If there is difficulty with mask ventilation, an oral airway may be used. • A difficult airway should be considered in patients with syndromes (Pierre Robin, Treacher Collins). – Be prepared to perform an awake fiberoptic intubation. – If an inhalational induction was performed and the patient is adequately spontaneously ventilating, supplemental IV sedation may be administered while a fiberoptic

bronchoscopy is performed. – Elective tracheostomy may be considered in patients with severe airway abnormalities. • An oral RAE is commonly utilized and taped to the middle chin line. Additional measures, such as benzoin and op-sites, may be used to secure the tube.

Maintenance

• The eyes should be securely taped and lubricated, as appropriate, to prevent trauma. • A balanced technique with volatile inhalation agents, opioids, and possibly nondepolarizing muscle relaxation. • A mouth gag is placed, along with a throat pack to provide good surgical visualization. This apparatus has a groove for the endotracheal tube and should sit in the groove without being occluded. Pay special attention to breath sounds and chest compliance during placement of the gag, as malposition can lead to partial or complete obstruction of the tube. The gag may also cause decreased perfusion of the tongue; it should be released intermittently to allow reperfusion. • Be aware of position changes. Flexion and extension of the neck may cause endobronchial intubation or inadvertent extubation. • Normothermia. A warming blanket should be used to prevent hypothermia. Hypothermia can delay emergence as well as cause metabolic acidosis (nonshivering thermogenesis of brown fat) with resultant respiratory and cardiac depression. • Blood loss. Although blood loss is rarely >10%, it should be monitored and transfusion should be considered when significant. • Local anesthetic infiltration done by the surgeon can provide postoperative pain control. • Nasopalatine and palatine nerve blocks (performed either by the surgeon or the anesthesiologist) can provide pain control of the hard and the soft palatal tissue, whereas an infraorbital nerve block can provide pain control for cleft lip surgery.

Extubation/Emergence

• If muscle relaxation was administered, adequate reversal with sustained tetany and train of four should be ensured prior to extubation. • Prior to extubation, the oropharynx should be gently suctioned with a soft catheter and the throat pack must be removed. The surgeon can perform the suctioning with the mouth gag in place under direct visualization. • Arm restraints or “welcome” sleeves are routinely used to keep the patient’s hands away from the face.

FOLLOW-UP • Medications: NSAIDS may increase bleeding and are typically avoided. Consider the use of low-dose narcotics, titrated to effect. • Labs: If the surgery was uneventful, none are indicated. Consider hemoglobin if there was increased bleeding. • Consults: If available, consider a pain consult.

BED ACUITY

• Hospital stay is warranted in a telemetry unit until the patient’s pain is controlled by oral pain medication and the child is able to tolerate oral feeds. • An intensive care unit (ICU) bed may be required for patients with ongoing airway obstruction for observation and management.

COMPLICATIONS

Surgical complications

• Infection • Bleeding, with or without aspiration • Delayed healing • Pneumonia • Airway obstruction can occur from closure of cleft structures, edema (subglottic, flap, tongue), increased oral secretions, posterior displacement of the tongue, or overlooked throat pack. A long traction suture is placed in the tongue and tied loosely; if needed, traction on the tongue suture stimulates respiration and clears the secretions. The use of an oral pharyngeal airway is not recommended.

REFERENCES

1. Mossey PA, Little J, Munger RG, et al. Cleft lip and palate. Lancet. 2009;374(9703):1773– 1785. 2. Vlastos IM, Koudoumnakis E, Houlakis M, et al. Cleft lip and palate treatment of 530 children over a decade in a single center. 2009;73(7):993–997WW. Vander Poorten V, Ostyn F, Van Kerckhoven W, et al. The Leuven staged supraperiosteal retropositioning repair: Long-term velopharyngeal function in non-syndromic cleft palate. B-ENT. 2006;2(Suppl 4):35–43. 3. Nasser M, Fedorowicz Z, Newton JT, et al. Interventions for the management of submucous cleft palate. Cochrane Database Syst Rev. 2008;23(1):CD006703.

ADDITIONAL READING

• “A Practice of Anesthesia for Infants and Children" By Charles J Cote, Jerrold Lerman, I. David Todres. Saunders/Elsevier (2009). See Also (Topic, Algorithm, Electronic Media Element)

• Upper respiratory infection • Hypothermia • Pierre Robin syndrome

CLINICAL PEARLS

• Syndromes may make intubation difficult; consider performing an awake fiberoptic intubation. • Airway obstruction after extubation requires careful attention. • Pain control during the postoperative period may be accomplished by nerve blocks.

Nasopalatine and palatine nerve blocks can be performed for soft and hard palate surgery; infraorbital blocks for cleft lip surgery.

CLOSING CAPACITY Kenneth R. Moran, MD

BASICS DESCRIPTION

• Closing capacity is the smallest lung volume that is required to prevent closure of small airways or alveoli. Closing Capacity (CC) = Residual Volume (RV) + Closing Volume (CV) • The ability to recognize patients at risk for decreased functional residual capacity (FRC) or increased CC can be useful to predict the degree to which intraoperative management will affect airway closure, shunt, and Alveolar-arterial (A-a) gradient. PHYSIOLOGY PRINCIPLES

• Bronchioles distal to the 11th generation are <1 mm and do not have rigid cartilaginous support to keep them open. These distal airways are subject to opposing forces that can prevent or maintain patency (1): – Outward elastic recoil of the chest wall (preventing airway collapse) and the opposing inward pull of the lung parenchyma; the sum of these opposing forces determine the intrapleural pressure (Ppl) at varying lung volumes. Note: The FRC is equal to the volume at which the Ppl is zero. – Surfactant maintains small airway patency by decreasing surface tension and collapse. – If the CC is greater than the total lung volume at any given point (inhalation or exhalation), premature airway closure results in distal lung segments that continue to receive perfusion, but are no longer ventilated. The shunting of unoxygenated blood from these segments into the arterial circulation can contribute to hypoxemia. • CC describes the lung volume at which any further exhalation results in airway closure. CV is the volume of air that can still be exhaled from the point of CC until only RV remains, during maximal exhalation. CV is usually less than the functional residual capacity (and expiratory reserve volume) in a healthy young adult in the standing position. • FRC is the resting point at the end of normal exhalation where elastic recoil of the chest equals inward lung recoil. It is the volume of air that remains in the lungs at the end of a normal tidal volume (TV) exhalation; FRC = ERV + RV. – RV is the volume of air left in the lung after a maximal expiration. During forced expiration, before exhalation to RV, small airway closure begins to occur as the CC is reached. • CC versus FRC. – CC < FRC. Small airways remain patent during normal TV. In young healthy patients, lung volume at the end of resting exhalation (FRC) is greater than CC (Figure 1).

FIGURE 1. Normal pulmonary function and its relationship to closing capacity. CC is represented by the dotted line.

– CC > FRC. If pathological or mechanical changes result in a reduction in FRC or an increase in CC, airway closure may occur during normal TV breathing (Figure 2).

FIGURE 2. A graphical representation of respiratory function in a person with decreased FRC and/or increased CC. Note how normal TV breaths result in lung volumes below CC. CC is represented by the dotted line.

• Since CC = CV + RV, changes in RV affect FRC and CC equally (FRC = ERV + RV). Thus, either a decrease in ERV or an increase in CV closes the gap between FRC and CC. An increase in CC signifies that airway closure occurs at higher lung volumes; in other words, while exhaling toward RV, closure occurs earlier. – CV increases with age, smoking, and COPD (2); factors that affect lung parenchyma elasticity. These airways become dependent on greater lung volumes to keep them open; as a result the CC rises (1). Additionally, it should be noted that CV is not dynamic like ERV and FRC and is unaffected by body positioning. – ERV (and FRC) is decreased in obesity, head down positioning, and general anesthesia as a result of decreased lung compliance. This is caused by pressure from adipose tissue on the lungs, diaphragm, and abdomen (3). ANATOMY

• Bronchioles • Alveoli • Ribs • Muscles of respiration

– Diaphragm – Intercostal muscles – Scalene muscles – Sternocleidomastoid muscles

DISEASE/PATHOPHYSIOLOGY

• Age, smoking, and lung disease can lead to a decrease in lung recoil (the force pulling the lung into itself) and an increase in lung compliance. • Changes in collagen fibrils and elastin in the lungs account for the increase in compliance and permit the lungs to inflate to larger volumes with less pressure. This results in larger lung volume requirements to keep small airways open and increases CC (1). Early airway closure, like atelectasis, can result in ventilation/perfusion (V/Q) mismatch where areas of unventilated lung may continue to receive perfusion. Areas of perfusion without ventilation, also known as shunt, can contribute to hypoxemia. • Aging increases both RV and CV. While changes in RV affect CC and FRC equally, an increase in CV will increase CC toward FRC (Figure 3). • CC, while supine, increases to equal FRC in one’s mid-forties and becomes greater than FRC, even when standing, in one’s mid-sixties. Eventually, exhalation of normal TV can bring lung volumes below CC resulting in airway closure during normal breathing (4). • Obesity does not affect the CC. It, however, diminishes chest and lung compliance, which ultimately decreases FRC. This reduction in FRC results from a reduction in ERV; RV is not affected (3). An obesity-associated reduction in FRC can result in lung volumes below the CC and early airway closure.

PERIOPERATIVE RELEVANCE

• Decreased FRC from supine positioning and general anesthesia can result in early airway closure when FRC falls below CC (CC > FRC). • General anesthesia reduces FRC by 0.4–0.5 L (5)[A]; this is presumed to occur from a loss of respiratory muscle tone and decreased chest wall compliance. Additionally, laying supine can reduce FRC by up to 1 L. When the FRC is reduced in this manner below CC, air trapping and shunting occurs. This has been hypothesized to be the cause of increased A-a gradient [P(A-a)O2] during surgery (6). This effect is further enhanced in patients with a baseline diminished FRC or elevated CC. Position and anesthesia do not affect the CC; however, they reduce the FRC, bringing it closer to the CC. • PEEP is often implemented to increase the FRC and improve the A-a gradient [P(A-a)O2] (5)

[A]. However, its use is limited since PEEP affects upper lung zones greater than lower zones. Conversely, airway closure occurs to a greater degree in the lower lung zones. In addition, an increase in intrathoracic pressure from PEEP may impede venous return and result in deterioration of cardiac output. • “Alveolar recruitment” may be achieved by applying a limited number of double TV breaths in an attempt to reopen closed airways and alveoli. An inflation pressure up to 30–40 cm H2O may be required (7)[A]. This must be done with caution as hemodynamic instability can result from an increase in intrathoracic pressure and decreased venous return. • Sitting a patient upright, or reverse Trendelenburg, >30° may increase FRC. This is useful

when trying to maximize respiratory function in the immediate postoperative period including extubation. • FRC remains decreased into the postoperative period. With reduced FRC, lung volumes are more likely to fall below CC during resting TVs, contributing to post-operative hypoxemia.

EQUATIONS

• CC = CV + RV • FRC = ERV + RV

REFERENCES

1. Wahba WM. Influence of aging on lung function—Clinical significance of changes from age twenty. Anesth Analg. 1983;62:764.

2. ilic-Emili J, Torchio R, D’Angelo E. Closing volume: A reappraisal (1967–2007). Eur J Appl Physiol. 2007;99:567–583. 3. Jubber AS. Respiratory complications of obesity. Int J Clin Pract. 2004;58:573. 4. Leblanc P, Ruff F, Milic-Emili J. Effects of age and body position on “airway closure” in man. J Appl Physiol. 1970;28:448–451. 5. Hedenstierna G, Edmark L. The effects of anesthesia and muscle paralysis on the respiratory system. Intensive Care Med. 2005;31:1327–1335. 6. Wahba RWM. Perioperative functional residual capacity. Can J Anaesth. 1991;38:384–400.

7. Rothen HU, Sporre B, Engberg G, et al. Re-expansion of atelectasis during general anesthesia: a computed tomography study. Br J Anaesth. 1993;71:788–795. 8. Nield MA, Hoo GWS, Roper JM, et al. Efficacy of pursed-lips breathing—A breathing pattern retraining strategy for dyspnea reduction. J Cardiopulm Rehabil Prev. 2007;27:237–244.

ADDITIONAL READING

• Alveolar-arterial gradient • Functional residual capacity • Spirometry • V/Q matching

CLINICAL PEARLS

• An increase in CC signifies that airway closure occurs at higher lung volumes. In other words, while exhaling, closure occurs earlier. • Premature small airway closure occurs as a result of decreased FRC and/or increased CC. It results in unventilated distal segments of lung that contribute to shunt and hypoxemia. • It is important to recognize patients at risk for early distal airway closure, such as those with advanced age, obesity, lung disease, or smoking history. • Patients with advanced COPD use pursed lip breathing to stabilize small airways and maintain their patency (8)[A]. Recognizing this breathing pattern can help identify patients

with advanced lung disease.

COCAINE ABUSE Nabil Elkassabany, MD

BASICS DESCRIPTION

• Cocaine is one of the oldest known psychoactive substances. Coca leaves have been chewed and ingested for thousands of years and the purified chemical, cocaine hydrochloride, has been a substance of abuse for more than 100 years (1). • Cocaine is available as a street drug in the form of a fine, white, crystalline powder. It is known as “coke,” “C,” “snow,” “flake,” or “blow.” It is frequently mixed with amphetamine or heroin; the latter combination is known as a “speedball.” • Today, it is used, legitimately, for its combined local anesthetic and vasoconstrictive effects (e.g., eye and ENT procedures and laceration repair in the emergency department); and is a Schedule II drug. It has been largely replaced by other local anesthetics that provide the same effects without the addictive potential. PHYSIOLOGY PRINCIPLES

• Mechanism of action. Blocks the reuptake of norepinephrine into the sympathetic nerve terminals; thus creates a sympathomimetic state (2). • Classification. Local anesthetic; ester • Pharmacokinetics – Peak plasma levels are attained within 1–3 minutes when inhaled or administered intravenously. – Plasma half-life ranges from 60 to 90 minutes – Metabolism is via plasma esterases. By-products include benzoylecgonine, ecgonine methyl ester (EME), and norcocaine. Some metabolites can be detected in the urine 3–5 days after ingestion. • Routes of administration include oral, intravenous, and transmucosal.

PHYSIOLOGY/PATHOPHYSIOLOGY

• CNS – Acute effects: Euphoria and heightened perception of space or time, irritability, restlessness, hyperthermia, and seizures (2). – Chronic effects: Physical dependence and addiction develop rapidly. Focal neurological deficits and coma have been reported; potential causes include vasoconstriction (transient ischemic attacks) and cerebral hemorrhage. – Withdrawal symptoms include fatigue, mental depression, and drug cravings. • Cardiac system – Acute effects: Tachycardia, hypertension, and coronary artery spasm can result in myocardial ischemia and/or myocardial infarction. Prolonged QT interval and ventricular arrhythmias can also result (3).

– Chronic effects: Left ventricular hypertrophy, systolic dysfunction, and dilated cardiomyopathy. • Respiratory system – Acute effects: Nonspecific respiratory complaints may be reported. Nasal bleeding and perforation of the nasal septum can result from snorting cocaine. “Crack lung” is a form of acute lung injury that has been reported after cocaine abuse (4). – Chronic effects: Diffuse alveolar infiltrates, alveolar damage, pulmonary infarction, and noncardiogenic pulmonary edema have been reported.

Pregnancy Considerations

• Low birth weight and premature delivery • Fetal intrauterine growth retardation (IUGR) has been attributed to decreased uteroplacental perfusion.

Pediatric Considerations

• Cognitive impairment and attention deficits are frequently encountered in children born to cocaine-abusing mothers. • Cocaine abuse among school children should not be overlooked. Recent data suggest declining numbers of 30-day prevalence of cocaine abuse among 8th, 10th, and 12th graders from its peak use in the late 1990s, as well as significant declines in past-month use among 10th and 12th graders from 2008 to 2009 (1). PERIOPERATIVE RELEVANCE

• Anesthetic implications of acute cocaine toxicity include the following: – Cardiac. An increased risk of perioperative myocardial ischemia, congestive heart failure (CHF), and ventricular arrhythmias. – CNS. An increased minimum alveolar concentration (MAC) requirement of inhaled anesthetic. • Preoperative evaluation – Obtain a detailed and complete history of substance abuse in every patient. – In patients with a positive history of abuse, associated comorbidities such as hypertension, coronary artery disease (CAD), arrhythmias, and CHF should be assessed. – Examine the nares – Labs. Urine drug screening can detect metabolites for up to 72–96 hours based on the halflife of the metabolite being tested. • Previously, cancellation was recommended for elective surgery in the event of a positive drug screening due to the potentially increased risk of perioperative myocardial ischemia. Recent evidence suggests that general anesthesia for elective procedures is possibly safe if the patient lacks symptoms and signs of acute cocaine toxicity on physical examination and has a QT interval <500 ms (5). • Perioperative care – Exercise caution when using beta-blockers in the context of acute cocaine toxicity. Unopposed alpha activity can result in coronary vasoconstriction. – Myocardial ischemia may be managed with short-acting beta-blockers (esmolol) and mixed alpha and beta-blockers (labetalol) to treat cocaine-induced myocardial ischemia.

– Hypotension during the course of the anesthetic is usually resistant to treatment with indirect-acting vasopressors (e.g., ephedrine). It is better treated with direct-acting vasopressors (e.g., neosynephrine). – If a nasal intubation is planned, be aware that the nasal mucosa can be atrophic and there is an increased prevalence of nasal perforation among cocaine abusers. – Regional anesthesia may be complicated by the following: Combative behavior. Adequate sedation should be provided. Altered pain perception Ephedrine-resistant hypotension with spinal or epidural anesthesia. Treatment should include intravenous fluid bolusing and direct-acting alpha agonists.

REFERENCES

1. National Research Report [http://www.nida.nih.gov/researchreports/cocaine]. Rockville, MD: National Institute of Drug Abuse. 2. lkassabany NM. Evidence Based Practice of Anesthesiology. 2nd ed. Fleisher LA, editor. Philadelphia, PA: Elsevier; 2010. 3. Lange RA, Hillis LD. Cardiovascular complications of cocaine use. N Engl J Med. 2001;345(5):351–358. 4. Baldwin GC, Choi R, Roth MD, et al. Evidence of chronic damage to the pulmonary microcirculation in habitual users of alkaloidal (“crack") cocaine. Chest. 2002;121(4):1231–1238. 5. Hill GE, Ogunnaike BO, Johnson ER. General anaesthesia for the cocaine abusing patient. Is it safe? Br J Anaesth. 2006;97(5):654–657.

ADDITIONAL READING

• Hernandez M, Birnbach DJ, Van Zundert AA, Anesthetic management of the illicitsubstance-using patient. Curr Opin Anaesthesiol. 2005;18:315–324. • Kuczkowski KM. The cocaine abusing parturient: A review of anesthetic considerations. Can J Anaesth. 2004;51(2):145–154.

See Also (Topic, Algorithm, Electronic Media Element) • Marijuana abuse • Alcohol abuse • The addicted anesthesia provider

CODES ICD9 • 304.20 Cocaine dependence, unspecified • 305.60 Cocaine abuse, unspecified ICD10

• F14.10 Cocaine abuse, uncomplicated • F14.20 Cocaine dependence, uncomplicated

CLINICAL PEARLS

• Cocaine abuse is often a mixed substance abuse problem. Inquire about other common drugs of abuse and their respective adverse effects in the perioperative period. • Cocaine abusers are at increased risk for HIV and viral hepatitis. This risk stems not only from sharing contaminated needles but also from engaging in risky behaviors as a result of intoxication. • The perioperative setting can be very helpful in providing drug counseling and referral to addiction clinics and behavioral intervention. Do not waste this opportunity. • Crack is the free base of cocaine that can be smoked. It is named after the sound it makes during manufacture and smoking. The onset of action is very quick and the peak effect is 1– 3 minutes. The resulting euphoria (the cocaine high) is the result of release of dopamine in the CNS. It is often mixed with other addictive substances. “Speedballing” is mixing cocaine with heroine that will obviously have more adverse effects.

COLLOIDS

Seth R. Cohen, DO Raymond M. Planisic, MD

BASICS DESCRIPTION

• Colloid solutions are comprised of large molecules dissolved in a crystalloid solution; when administered these molecules help maintain intravascular oncotic pressure. • They are divided into two groups – Natural colloids, such as albumin – Semisynthetic colloids, including gelatins, dextrans, and hydroxyethyl starches • The goal of fluid administration is to improve organ perfusion through optimization of volume status (1)[A]. Colloids can be utilized perioperatively to aid volume expansion. PHYSIOLOGY PRINCIPLES

• Total body water (TBW) – Comprises 60% of body weight and is measured in kilograms. – Two-thirds is intracellular fluid (ICF) – One-third is extracellular fluid (ECF); of which 80% is interstitial, while the remainder is intravascular. – Varies with age, sex, pathologic conditions, and other factors. • Starling forces define flow from intravascular to interstitial/extravascular space. Intravascular oncotic pressure opposes the filtration or hydrostatic process (see equations). Net driving force or net filtration is determined by the following factors (pressures are measured in mm Hg). – Capillary hydrostatic pressure (Pc) favors filtration across the capillary endothelium into

the interstitium. – Interstitial hydrostatic pressure (Pi) drives fluid back into the capillaries and therefore

opposes filtration of capillary fluid into the interstitial fluid. – Capillary oncotic pressure prevents movement of solvent and small ions across the capillary membrane, thereby opposing filtration. – Interstitial oncotic pressure prevents movement of solvent and small ions across the capillary membrane, favoring filtration. – Filtration coefficient is comprised of capillary surface area and capillary hydraulic conductance. Increased water permeability is demonstrated by an increased value. – Reflection coefficient functions to account for the small permeability of albumin and other proteins. Protein permeability results in greater than expected oncotic pressure in interstitial fluids. • Crystalloids are composed of ionized salts and water-soluble molecules dissolved in water. – The salts and molecules provide electrolytes and osmolarity but not oncotic pressure.

– Crystalloids can freely diffuse across intravascular endothelial walls into the interstitium. – In theory, ~20–30% of crystalloid solution infused will remain intravascular. • Colloids are composed of large molecules that provide oncotic pressure and are suspended in a crystalloid solution. The molecules do not easily cross semipermeable membranes. – Molecular weight (MW) of the colloid is proportional to size; larger molecules are less easily filtered (higher reflection coefficient). – Those molecules that are not filtered by the kidneys are eventually taken up by the reticuloendothelial system or excreted through the gut. – Balanced solutions (isotonic) have less adverse effects than normal saline (hyperchloremic metabolic acidosis). • Albumin (MW 69 kDa) is made from pooled human plasma that has been heated (60°C for 10 hours), screened for viruses, and ultrafiltered. – Monomer; all molecules have the same size. – Available in a 5% (isooncotic) for volume expansion and 25% (hyperoncotic) solutions for hypoalbuminemic states (1)[A]. – Expanding effects may last between 16 and 24 hours. • Gelatins are produced from bovine collagens. While they provide high osmotic pressure, their low molecular size allows them to be rapidly filtered by the glomeruli; overall they produce similar volume expansion to crystalloids. – Least likely of the colloids to affect hemostasis. – Half-life has been reported to be 3.5–4 hours. – New generation gelatins (e.g., Polygeline, Plasmagel) have been developed and have higher molecular size (greater oncotic pressure), but are not commonly used in the US. • Dextrans are highly branched polysaccharide molecules produced by bacteria containing dextran sucrose that grows on sucrose medium. – Available in 10% dextran 40 (MW 40 kDa) and 6% dextran 70 (MW 70 kDa). Dextran 70 resembles human albumin in regard to MW. – Dextran 40 promotes microvascular blood flow in vascular surgery by decreasing red blood cell (RBC) aggregation, but is rapidly filtered by the kidneys and not used for volume expansion. – Dextran 70 is capable of up to 100–150% volume expansion with maximal expansion reached ∼1 hour after infusion. Dextran 70 has expanding effects that last between 6 and 12 hours. • Hydroxyethyl starches are made of amylopectin modified through hydrolysis and hydroxyethyl substitution. – Capable of up to 100% volume expansion. – With greater substitution, the molecule becomes more resistant to degradation in the body and the duration of its expansion effects also increase compared to other colloids. – Hespan is presented in normal saline, while Hextend comes in a balanced electrolyte solution (1). – Believed to have anti-inflammatory properties and to preserve intestinal microvascular perfusion in endotoxemia. – Does not appear to interfere with coagulation at doses <50 mL/kg. – Molecules <50,000 kDa are excreted by the urine within 24 hours; the larger molecules

are slowly degraded enzymatically to molecules small enough to be excreted.

DISEASE/PATHOPHYSIOLOGY

• The most commonly accepted indications of colloid administration is for the treatment of hypoalbuminemic states in the presence of salt/water overload (1) and replacing blood loss prior to blood administration (2). Hypoalbuminemia can result from reduced production (liver disease) or increased loss (renal disease). Serum albumin normally comprises ∼50– 60% of plasma proteins. It functions as a carrier of intermediate metabolites, trace metals, drugs, dyes, fatty acids, hormones, and enzymes, and hence affects the transport, inactivation, and/or exchange of tissue products. • Adverse effects of colloids – Increased vascular permeability is often seen in the setting of surgical tissue trauma, hypoperfusion states, trauma, sepsis, and burns. This can result in oncotic molecules entering the interstitial compartment and edema formation (net driving force favors fluid movement out of the intravascular compartment). – The use of colloids in trauma patients may be associated with an increased mortality, especially in patients with traumatic brain injury (1). – Volume overload • Gelatins – Greatest risk of anaphylactic reactions. – Theoretical risk of Creutzfeldt–Jacob disease (CJD) (2). • Dextrans – Can cause coagulopathies from reduced platelet adhesiveness and dilution of factor VIII as well as fibrinolysis. – Can interfere with the ability to cross-match blood, by coating the RBC surface. If administered, the blood bank should be informed. – May result in acute renal failure due to accumulation of molecules in the renal tubule. – Anaphylaxis can be reduced by pretreating with dextran 1, which acts as a hapten to bind antibodies. • Hespan – Coagulopathies can occur from reduced circulating factor VIII and von Willebrand factor levels and impaired platelet function; manifests as a prolonged PT and PTT. – Pruritus – Anaphylaxis – Renal impairment, higher creatinine levels, oliguria, and acute renal failure in patients who were critically ill with existing renal impairment. – Can increase amylase levels, which is typically not clinically significant. – May increase the erythrocyte sedimentation rate.

PERIOPERATIVE RELEVANCE

• Controversy exists over the use of colloids for volume resuscitation. Outcome studies have not supported its use over crystalloids. • Arguments for the use of colloids – Venodilation from anesthetics can decrease preload and exacerbate hypovolemic states. If necessary, colloids can be used for rapid expansion of plasma volume, while limiting total

volume load and peripheral edema (2). Traditionally, intraoperative blood loss has been replaced with 3 mL crystalloids or 1 mL colloids for every 1 mL blood loss (3). – Theoretically can increase oncotic pressure and provide greater volume expansion than crystalloids. – Do not require special preparation and are immediately available while awaiting blood products. – May be utilized in Jehovah’s witnesses (though some object to albumin). – Less peripheral and pulmonary edema with associated impaired function. In particular, during intra-abdominal procedures, intestinal edema may result from excessive fluid administration, which has been associated with significant postoperative complications (3) [A]. • Arguments against colloids – Recent Cochrane review and Saline versus Albumin Fluid Evaluation (SAFE) Study Subgroup analysis have found a possible increase in mortality in using colloids in trauma, especially patients with traumatic brain injury (1)[A]. – Cochrane subgroup analysis has also linked colloid use with an increased risk of death in hypoalbuminemic and burn patients (4). – The use of crystalloids remains the mainstay in acute resuscitation of the trauma patient, per advanced trauma life support (ATLS) guidelines (5).

EQUATIONS

Jv = k[(Pc – Pi) – σ(πc – πi)], where Jv = vascular flow, k = filtration coefficient, Pc =

intravascular hydrostatic pressure, Pi = interstitial hydrostatic pressure, σ = reflection

coefficient of the colloids, π c = intravascular colloid pressure, πi = interstitial colloid pressure (4).

REFERENCES

1. Vercueil A, Grocott MP, Mythen MG. Physiology, pharmacology, and rationale for colloid administration for the maintenance of effective hemodynamic stability in critically Ill patients. Transfus Med Rev. 2005;19:93–109. 2. Grocott MP, Mythen MG, Gan TJ. Perioperative fluid management and clinical outcomes in adults. Anesth Analg. 2005;100:1093–1106. 3. Chappell D, Jacob M, Hofmann-Kiefer K, et al. A rational approach to perioperative fluid management. Anesthesiology. 2008;109:723–740. 4. Finfer S, Bellomo R, McEvoy S, et al. Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: Analysis of data from the saline versus albumin fluid evaluation (SAFE) study. Br Med J. 2006;333(7577):1044. 5. Van Den Elsen MJ, Leenen LP, Kesecioglu J. Hemodynamic support of the trauma patient. Curr Opin Anaesthesiol. 2010;23:269–275.

CLINICAL PEARLS

• Although colloids are more expensive, they can produce a quicker restoration of intravascular volume status. • The SAFE study showed no benefit or increased mortality in use of albumin versus saline in an intensive care unit (ICU) setting (5)[A]. • Adverse effects of colloid use include renal impairment, decreased hemostasis, anaphylactic reactions, and pruritus (1,4)[A]. • Choice of fluids remains controversial and pros/cons must be weighed with each fluid type and clinical situation. • Some authors have advised the use of crystalloid to replace fluid losses from insensible losses and urinary output, while replacing blood loss and protein-rich fluid shifts with colloids (4). • Monitors to assess volume status. Central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP) are most commonly used to guide volume status, but do not always reliably predict fluid response. Other measures include cardiac output or index, pulse pressure variation, stroke volume variation, systolic pressure variation, and esophageal Doppler. Lactate levels and base deficit are signs of tissue perfusion (5)[B]. • The ideal colloid should be: – Capable of remaining in the intravascular compartment – Non-toxic, non-immunogenic – Isotonic – Easy to store – Inexpensive

COLONOSCOPY Edna Ma, MD

BASICS DESCRIPTION General

• A colonoscopy is an endoscopic procedure performed with a fiberoptic camera to examine the colon, from the anus to the distal portion of the small bowel (e.g., terminal ileum). • Colonoscopies are indicated for colorectal cancer screening, positive fecal occult blood, GI hemorrhage, removal or biopsy of small polyps, change in bowel habits (associated with inflammatory bowel disease or malignancy), or decompression (as with colonic pseudoobstruction). • Colonoscopies can be performed under topical anesthesia with or without conscious sedation (benzodiazepines and opioids) or deep sedation (typically propofol). Position

Lateral decubitus

Approximate Time 15–45 minutes EBL Expected

None to minimal, unless associated with underlying condition (e.g., GI hemorrhage or coagulopathy). Hospital Stay

• The majority of colonoscopies are outpatient procedures. • For inpatients, the duration of the hospital stay depends on the underlying conditions.

Special Equipment for Surgery

• Endoscopic colonoscope • Irrigation • Suction • India ink for tattooing polyp site

EPIDEMIOLOGY Prevalence

• Incidence of colon cancer increases with age, beginning around 40 years of age, and is higher in men than in women (60.4 in men versus 40.9 in women, per 100,000, per year) (1). • Propofol sedation is utilized in ∼25% of routine endoscopic procedures, of which the

majority are performed by anesthesia providers. • In 2003, Medicare charges for code 00810 were 106 per case; this compared to an average of 400 per case from commercial insurers (2). • In Medicare beneficiaries, the number of colonoscopy cases performed by anesthesia providers more than doubled between 2001 and 2003 to 700,000; this corresponded to $80,000,000 in charges (2). Prevalence

The lifetime risk of being diagnosed with colorectal cancer is 5.9% for men and 5.5% for women. This amounts to ∼145,290 new cases and 55,290 deaths annually. Morbidity

• Colorectal cancer survival is correlated to the stage of the disease at the time of diagnosis. Approximately 65% of patients present with advanced disease. • Colonoscopy is a low-risk surgical procedure, but it has the potential for perforation and bleeding. • Anesthetic risks include those associated with sedation, allergies, and nausea.

Mortality

• Colorectal cancer is the third most common cancer in both men and women and the third leading cause of cancer-related mortality in men and women in the US (3). • Five-year survival for cancer limited to the bowel wall at the time of diagnosis approaches 90%. When lymph nodes were involved, the 5-year survival dropped to 35–60%; and in the presence of metastatic disease it became less than 10% (4). ANESTHETIC GOALS/GUIDING PRINCIPLES

• Efficiency, safety, and patient satisfaction must be provided; standard ASA monitoring as well as airway equipment and emergency medications must be available. • Patients arriving for routine screening colonoscopies often present after having bowel preparations and they may be dehydrated, particularly for cases scheduled later in the day. • Patients suspected of having a history of colon cancer may have mild anemia. The anemia may be more severe depending on the extent of disease and may warrant transfusion. • Risk of aspiration is more significant for patients with a history of obstruction (including pseudo-obstruction) as bowel contents may travel in a retrograde direction. • Decreases in functional residual capacity (FRC) are associated with cephalad displacement of the diaphragm, which is more pronounced during insufflation of the colon and in patients with severe obstruction or impaction.

PREOPERATIVE ASSESSMENT SYMPTOMS

Anemia (occult blood, indicating proximal colon involvement, or “bright red blood per rectum” [BRBPR], suggesting distal colon lesions). This can manifest as pallor or fatigue, or in more severe cases, with lightheadedness, shortness of breath, or chest pain.

History

• A full anesthetic evaluation is necessary; patients who present for anesthetic management often have significant comorbidities. • Maintain a high index of suspicion for colon cancer in elderly patients that present with a change in bowel habits, a history of fatigue or weight loss, particularly if there is a strong family history of colorectal cancer. Signs/Physical Exam

• A thorough airway exam is important in the event that the airway needs to be supported or secured. • Auscultation of the heart and lungs at a minimum is necessary for each patient.

MEDICATIONS

• Patient specific; related to patient comorbidities. • Chemotherapeutic agents in patients with a history of colon cancer.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Preoperative laboratory studies for routine screening and ambulatory cases are not typically needed. If available, however, they should be reviewed. • For inpatients, a hemoglobin level, coagulation panel and electrolyte values may have already been obtained and should be reviewed; consider ordering if appropriate. CONCOMITANT ORGAN DYSFUNCTION

Concomitant organ dysfunction may occur if metastatic colon cancer is present. Primary organs involved include the liver, lung, and bones.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics, analgesics as needed. Short acting medications (e.g. midazolam, fentanyl) should be utilized. • GI prophylactic medications include acid reduction agents.

Special Concerns for Informed Consent

• Realistic sedation goals should be discussed, including the possibility of recall. • If a patient has severe anemia, a blood transfusion may be necessary.

INTRAOPERATIVE CARE Choice of Anesthesia

• Monitored anesthesia care (MAC) is commonly provided for screening and outpatient procedures using propofol; common adjuvants include midazolam and fentanyl. The goal is

to maintain spontaneous ventilation. • General anesthesia (GA). Despite maintaining spontaneous ventilation and not instrumenting the airway, some anesthetists consider the depth of “sedation” needed for a colonoscopy as falling under the criteria of a general anesthetic. Inpatients may need their airway secured with an endotracheal tube.

Monitors

• Standard ASA monitors • IV access

Induction/Airway Management

• MAC: Supplemental oxygen with nasal cannula or face mask. Titration of sedation can be performed with benzodiazepines, opioids, propofol, or ketamine. • GA: Spontaneous ventilation, laryngeal mask airway, or endotracheal tube.

Maintenance

• Sedation is typically performed with IV medications and titrated to maintain spontaneous ventilation. • Volatile agents may be administered via a face mask or an endotracheal tube.

Extubation/Emergence

• MAC and deep sedation: Re-orient the patient. • GA with an endotracheal tube: Standard extubation criteria.

FOLLOW-UP BED ACUITY

• The majority of colonoscopies are done on an outpatient basis. • Comorbid conditions should dictate the level of care for inpatients. • Intensive care unit (ICU) patients may have their procedure performed at the bedside to avoid transport.

ANALGESIA

Not typically needed COMPLICATIONS

• Surgical-related • Perforation from biopsy instrumentation • Bleeding from polypectomy site • Postpolypectomy syndrome (also known as transmural burn syndrome) • Infection from inadequate sterilization equipment • Anesthetic-related • Airway obstruction and desaturation • Nausea

PROGNOSIS

Survival is directly related to early detection, cancer type, and stage. Tumors that have not invaded the muscular mucosa (TNM stage T1–2, N0, M0) have a 5-year survival of ∼90% (5).

REFERENCES

1. Report: Number 1. AHCPR Publication No. 97-0302. Agency for Health Care Policy and Research, Rockville, MD. http://www.ahrq.gov/clinic/colorsum.htm 2. isenberg J, Brill JV, Ladabaum U, et al. Sedation for gastrointestinal endoscopy: New practices, new economics. Am J Gastroenterol. 2005;100:996–1111.

3. Cancer Trends Progress Report (http://progressreport.cancer.gov), in 2004 dollars, based on methods described in Medical Care. 2002;40(8 Suppl):IV-104–117. 4. Jeffery M, Hickey BE, Hider PN. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev. 2002;(1). 5. esch CE, Benson AB 3rd, Somerfield MR, et al. American Society of Clinical Oncology. Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2005;23(33):8512–8519. 6. Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline. 7. Standards of Practice Committee. Sedation and anesthesia in GI endoscopy. Gastrointestinal Endoscopy. 2008;68(5):815–826. www.theasahq.org See Also (Topic, Algorithm, Electronic Media Element) • Upper gastrointestinal endoscopy • Propofol

CODES ICD9 V76.51 Special screening for malignant neoplasms of colon ICD10 Z12.11 Encounter for screening for malignant neoplasm of colon

CLINICAL PEARLS

• Colonoscopies can be performed with topical anesthesia with or without conscious sedation, or with MAC, deep sedation, or GA. • “Who is qualified to give propofol?” is a topic that has been addressed by several committees and even legislative bodies. • Access to anesthesia providers is a key factor. • Payor policies also affect the rate of anesthesia provider utilization in different regions of the country.

• Most insurance carriers and Medicare require that “supporting documentation should identify patient-specific reasons such as reports from prior endoscopies indicating difficulty in completing the procedure; or unusual discomfort during the procedure; or evidence of an unstable medical condition.” • The routine assistance of an anesthesia provider for average-risk patients undergoing standard upper and lower endoscopic procedures is believed to be cost-prohibitive. • A full preoperative history and evaluation as well as consent should be attained on all patients.

COMBINED SPINAL-EPIDURAL (CSE) Benjamin Abraham, MD

BASICS DESCRIPTION

• The combined spinal-epidural analgesia (CSE) technique is used to deliver local anesthetic (LA) (+/– adjuvant medications) into both subarachnoid and epidural spaces in one multistep procedure. • Advantages of the CSE technique include the following: – Rapid onset of analgesia – Minimal drug dosing – The flexibility of continuous epidural analgesia (Figure 1).

FIGURE 1. CSE technique: The Tuohy needle is inserted into the epidural space (top left) and a spinal needle is inserted

through it. The pencil-point spinal needle may deform the dura considerably before puncturing it (top middle). After

injection through the spinal needle, it is withdrawn, and an epidural catheter is inserted (bottom left), and the epidural needle is withdrawn (bottom right). (Adapted from Eisenach JC. Combined spinal-epidural analgesia in obstetrics. Anesthesiology. 1999;91(1): 299–302).

PHYSIOLOGY PRINCIPLES

• CSE kits. A wide variety of commercially available kits can be used. Although they vary by institution and manufacturer, they contain the following basic standard items: – Hollow bore epidural needle: To identify and access the epidural space and to function as an “introducer” needle by which the spinal needle is inserted. Most commonly, a Tuohy needle (16–18 gauge) is utilized. – Loss of resistance syringes: Available in glass or plastic. – Spinal needle: A long pencil-point (≤27 gauge) needle – Epidural catheter • Technique – Usually, the epidural needle is inserted at a lower lumbar level (at the level of the cauda

equina), to minimize injury to the spinal cord. Identification of the epidural space relies on tactile sensation, with a subtle change in resistance identified by the injection of either saline or air; known as the “loss of resistance” technique. Identification of the subarachnoid space. The spinal needle is passed through the hollow epidural needle. No additional introducer is needed. – Identification of the subarachnoid space depends on the return of cerebrospinal fluid. Medications are then injected and the spinal needle is removed. – Indwelling epidural catheter insertion. The catheter is threaded through the epidural needle, usually with 4–5 cm of catheter lying in the epidural space. It allows for medication delivery either as repeat boluses or continuous infusion. Typically, an epinephrine-containing test dose is used to detect intravascular injection once the epidural catheter is positioned. • Subarachnoid medications – Opioids. Sufentanil (5–10 μg) or fentanyl (20–35 μg) can be used to provide rapid analgesia (usually within 5 minutes) for the first stage of labor, and will last for ∼90 minutes. Long-acting drugs such as preservative-free morphine are obviated by the ability to deliver a continuous epidural infusion. Furthermore, intrathecal injection of morphine is associated with unacceptably slower analgesia, and delayed-onset respiratory depression occurring 6–12 hours after the injection, making it an unnecessary addition to a CSE. Meperidine has LA-like effects that would make it an ideal drug for subarachnoid injection; however, has been associated with severe hypotension and is rarely is used in modern practice. – LA. Combining Bupivacaine 2.5 mg with intrathecal opioid will prolong the duration of analgesia and decrease the failure rate of CSE in the later stages of labor. A number of small studies have demonstrated inferior analgesia with hyperbaric solutions when compared to isobaric preparations. – Adjuncts. The addition of epinephrine 200 μg or clonidine 50 μg can further increase duration of analgesia. The increased risk of medication error and compounded side effect profiles (including increased motor block with epinephrine or sedation and hypotension with clonidine) have limited the use of multiple additives to intrathecal solutions. • Continuous epidural infusions can be initiated shortly after the CSE is completed and maternal hypotension and fetal adverse effects have been ruled out. If equipment and patient understanding allows, patient-controlled epidural analgesia can be started using parameters typical for any other post-operative patient.

ANATOMY

• The patient can be positioned in the sitting or lateral decubitus position for the procedure. • Similar to the technique used to place an epidural catheter alone, the Tuohy needle is inserted into the skin and traverses the – Subcutaneous fat and tissue – Supraspinous ligament – Interspinous ligament – Ligamentum flavum – Enters into the epidural space • Using a needle-through-needle technique, the spinal needle is inserted into the Tuohy needle

to pierce the dura.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Postdural puncture headache (PDPH). Various investigators have shown that the use of a pencil-point spinal needle for a CSE does not result in an increased incidence of PDPH. • “Wet tap.” Accidental puncture of the dura with an epidural needle can be managed by threading a soft epidural catheter into the intrathecal space, in order to minimize the risk for PDPH. The catheter can be used for continuous spinal analgesia during labor or surgery. Clear labeling of the catheter as “INTRATHECAL” is imperative to avoid overdose. Obviously, infusion rates must be adjusted for continuous intrathecal, rather than epidural infusion. It is postulated that local inflammation of the dura around the catheter aids in sealing of the puncture, when the catheter is removed 24–48 hours after placement. • Total spinal anesthesia. Rare event most often due to medication error or inadvertent placement of the epidural catheter in the intrathecal space. This can be detected when a dense spinal blockade occurs following test dose. • LA toxicity. No additional risk of direct LA toxicity is involved with CSE when compared to epidural alone. • Inadvertent intrathecal catheter. Entrance of the epidural catheter into the intrathecal space is unlikely without dural puncture by the Tuohy needle, given the comparatively smaller size of the hole produced by the spinal needle. • Pruritus. Spinal opioids are associated with pruritus in >80% of cases. • Hemodynamics. – Maternal hypotension can result from spinal opioids in up to 20% of patients. – Fetal bradycardia (transient) can occur in up to 5% of patients. The mechanism is believed to result from the abrupt decrease in circulating catecholamines that follows the rapid and intense analgesia of CSE. This leads to an increase in uterine contractions with resultant bradycardia until a new equilibrium is established. • Respiratory. Maternal respiratory depression is uncommon, but has been reported to occur in 0.1% of patients. • Inadequate analgesia, unrecognized failed or patchy epidural • Less common procedural complications can include persistent back pain, infection (meningitis, epidural abscess), and epidural hematoma. • Nerve injury. No additional risk is conferred with the use of CSE besides those inherent in either the spinal or epidural components themselves. • Mortality. No differences were found when CSE was compared to either a spinal or epidural placement.

PERIOPERATIVE RELEVANCE

• Indications. Labor analgesia, C-section, abdominal surgery, and lower extremity procedures when rapid onset of block and titratablility of level and density is required. The level of blockade can be adjusted by increasing the epidural infusion rate. • Contraindications. No additional contraindications when compared to epidural or spinal analgesia. This includes local infection or bacteremia, prior spine surgery at that level, anticoagulation and proven allergy to any component of the CSE. Use of pencil-point, rather than cutting needle with CSE (or simply epidural analgesia alone), should be considered in

patients with history of PDPH.

REFERENCES

1. Collis RE, Davies DW, Aveling W. Randomised comparison of combined spinal-epidural and standard epidural analgesia in labour. Lancet. 19953;345(8962):1413–1416. 2. Choi DH, Kim JA, Chung IS. Comparison of combined spinal epidural anesthesia and epidural anesthesia for cesarean section. Acta Anaesthesiol Scand. 2000;44(2):214–219. 3. Eisenach JC. Combined spinal-epidural analgesia in obstetrics. Anesthesiology. 1999;91(1):299–302.

4. Dennison B. Combined subarachnoid and epidural block for caesarean section. Can J Anaesth. 1987;34(1):105–106. 5. Ferouz F, Norris MC. Baricity, needle direction, and intrathecal sufentanil for labor analgesia. Anesthesiology. 1997;86:592–598. 6. Holmstrom B, Laugaland K, Rawal N. Combined spinal-epidural block versus spinal and epidural block for orthopedic surgery. Can J Anesth. 1993;40:601–606 See Also (Topic, Algorithm, Electronic Media Element)

• Epidural • Postdural puncture headache

CLINICAL PEARLS

• CSE analgesia offers many of the advantages of each of its component techniques. • Patient satisfaction is high with the technique due to its rapid onset of almost complete analgesia in the 1st stage of labor. • The CSE technique can be used to increase the block height, or supplement a patchy subarachnoid block for surgery. • Special concerns for informed consent: Disclosure of both maternal and fetal risks as mentioned above.

COMPLEX REGIONAL PAIN SYNDROME (CRPS) TYPE I Andrew Fond, MD Eric S. Hsu, MD

BASICS DESCRIPTION

• Formerly known as reflex sympathetic dystrophy (RSD), complex regional pain syndrome I (CPRS Type I) is a chronic neuropathic pain disorder characterized by the following: – A nonspecific extremity injury – No definable nerve injury – Autonomic nervous system (ANS) involvement with features such as local edema as well as altered sweating, skin color, and temperature. – Signs of neuropathic pain such as intense burning pain, hyperalgesia, and allodynia. • It differs from CRPS Type II only in that it lacks a documented or definable nerve injury.

EPIDEMIOLOGY Prevalence

• A calculated at-risk incidence of ∼5.5 per 100,000 person years. • 50,000 anticipated new cases in the US annually. • Postfracture incidence reaches ∼1–2%.

Prevalence

• Prevalence of ∼21 per 100,000 person years • Estimated female:male ratio of 3:1 • Mean age of diagnosis 36–42 years of age

Morbidity

• Permanent disability: 31% • Need to make working adjustments: 28%

ETIOLOGY/RISK FACTORS

• Crush injuries • Strains and sprains • Fractures • Surgery, especially after trauma • May develop after virtually any injury

PHYSIOLOGY/PATHOPHYSIOLOGY

• Altered cutaneous innervation (1) – Following the initial injury, there is decreased C-fiber and A Delta-fiber density in the affected limbs of CRPS Type I patients compared with nonpainful control sites on the

same extremity and compared with healthy controls. • Peripheral nervous system sensitization – After tissue trauma, primary afferent fibers in the injured area release several neuropeptides that increase background firing of nociceptors and increase firing in response to nociceptive stimuli; this contributes to hyperalgesia and allodynia. • Central nervous system sensitization – Persistent or intense noxious stimuli resulting from tissue damage appear to trigger increased excitability of nociceptive neurons in the spinal cord. • Inflammatory mediators – Increased levels of local, systemic, and CSF proinflammatory mediators. – Decreased systemic levels of anti-inflammatory cytokines • CNS (brain) plasticity – There is a reduction in size of the representation of the CRPS-affected limb in the somatosensory cortex compared with the unaffected side. – The degree of somatotopic reorganization correlates with CRPS pain intensity and degree of hyperalgesia. – Psychological factors – Greater preoperative anxiety may prospectively predict acute CRPS symptomatology after total knee arthroplasty. – Emotional arousal has a greater impact on pain intensity in CRPS than in non-CRPS chronic pain, possibly via association with catecholamine release.

PREVENTATIVE MEASURES

• Calcitonin injection was shown in one study to decrease the frequency of CRPS in hemiplegic patients after stroke. • Vitamin C 500 mg/day reduced the incidence of CRPS after wrist fractures in clinical studies.

PREOPERATIVE ASSESSMENT • CRPS Type I is a clinical diagnosis formulated by bedside history and physical examination. Clinicians may use technical testing procedures to corroborate or objectively document their clinical impressions. • The modified diagnostic criteria for CRPS were published in 2007 (2). – Pain is continuing and disproportionate to any inciting event. – For clinical use, patient must report 1 symptom in 3 or more of the following categories. Sensory: Hypesthesia and/or allodynia Vasomotor: Temperature asymmetry (>1°C) and/or skin color changes or asymmetry. Sudomotor/Edema: Edema and/or sweating changes or asymmetry Motor/Trophic: Decreased range of motion and/or motor dysfunction or trophic changes (hair, nail, skin) – There must be 1 sign in 2 or more of the following categories upon physical examination: Sensory: Evidence of hyperalgesia (to pinprick) and/or allodynia (to light touch and/or temperature sensation and/or deep somatic pressure and/or joint movement) Vasomotor: Evidence of temperature asymmetry (>1°C) and/or skin color changes

and/or asymmetry Sudomotor/Edema: Evidence of edema and/or sweating changes and/or sweating asymmetry Motor/Trophic: Evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin) – There is no other diagnosis that better explains the signs and symptoms in CRPS. • Three-phase bone scintigraphy may help to demonstrate osseous changes and uptake during the subacute period (up to 1 year). However, there is no gold standard to compare with the findings. • A pathological uptake in the metacarpophalangeal or metacarpal bones is thought to be highly sensitive and specific for CRPS. • Plain radiographs and x-ray bone densitometry: Spotty and localized bone demineralization has been observed only in chronic stages of CRPS. • Quantitative sensory testing (QST) is a psychophysical testing of thermal pain and vibratory thresholds that may help to assess the function or dysfunction of myelinated and unmyelinated afferent fibers. However, there is no sensory profile that is characteristic for CRPS. • Autonomic function can be evaluated by the following points: – Infrared thermometry measures the skin temperature difference between the affected and normal limbs at resting and controlled modulation of sympathetic function. – Quantitative sudomotor axon reflex test (QSART) can assess the function of sudomotor (sweating) reflex loops. Swelling can be quantified by measuring water displacement.

DIFFERENTIAL DIAGNOSIS

• Posttraumatic neuralgia • Diabetic and other small fiber neuropathies • Entrapment neuropathy • Thoracic outlet syndrome • Vascular insufficiency • Infection such as cellulitis • Reynaud’s disease

TREATMENT • Focused around pain management (pharmacologic and interventional), rehabilitation, and psychological therapy (4). • Pharmacologic interventions – Tricyclic antidepressants (TCA) are a first-line agent. Although there are no controlled studies specifically for CRPS, they are the best-studied group of pharmacological agents in various neuropathic pain syndromes. Amitriptyline 10–75 mg PO per day; nortriptyline 10–75 mg PO per day; desipramine 10–75 mg PO per day. All TCAs have similar side effects including sedation and anticholinergic effects. – The efficacy of selective serotonin reuptake inhibitors (SSRI) in neuropathic pain states is not well documented.

– Anticonvulsants such as gabapentin and pregabalin have been studied for postherpetic neuralgia and diabetic neuropathy. Gabapentin 900–3600 mg/day PO divided into t.i.d. dosing was shown to provide benefit of sensory deficit symptoms in addition to mild pain relief. Alternatively, pregabalin (Lyrica) 150–600 mg/day PO divided into BID or TID dosing can be used. Anticonvulsants are commonly used off-label in CRPS as a first-line agent. Side effects include somnolence, dizziness, and peripheral edema. – Opioids are used as second-line agents to provide analgesia and facilitate functional rehabilitation. The use of opioids in neuropathic pain revealed efficacy when compared to placebo. There is no long-term study of opioids in neuropathic pain or CRPS. Tramadol, morphine sulfate, and oxycodone have been studied in treatment of neuropathic pain. – NSAIDS have not been studied in CRPS. It may control mild-to-moderate pain in clinical practice as a second-line agent for inflammation and edema. – Corticosteroids: Oral prednisolone 10 mg TID has been studied in the acute (<13 weeks) stage of CRPS. – N-methyl-D-aspartate receptors antagonists have been studied to reduce central sensitization. Although ketamine has provided favorable outcomes in case reports, wellcontrolled studies for ideal dosing in CRPS are still pending. – Clonidine transdermally administered may prevent the release of catecholamines via presynaptic actions. – Lidocaine 5% patch is approved for postherpetic neuralgia and has been used anecdotally in CRPS. – Calcitonin 100–300 IU/day intranasally may be effective. Clonodronate 300 mg IV QD or aldrenoate 7.5 mg IV QD have both demonstrated improvement in pain, swelling, and range of movement in acute CRPS. – Gamma-aminobutyric acid (GABAB) agonists: Intrathecal baclofen up to 450 μg/day has

been used for the treatment of dystonia associated with CRPS. • Interventional therapy – Epidural clonidine may provide greater pain reduction at higher dosages (700 μg) compared to lower dosages (300 μg) in CRPS, but may be associated with sedation and hypotension. Epidural local anesthetics and/or steroids have not been studied in the treatment of CRPS Type I. – Peripheral nerve blocks in CRPS Type I do not provide diagnostic or therapeutic benefit as in CRPS Type II. – Paravertebral sympathetic ganglion blocks: Stellate (cervicothoracic) ganglion block for the upper extremity and lumbar sympathetic block for the lower extremity can help to differentiate if pain has a strong sympathetically mediated component or if it is sympathetically independent (level 4 evidence). – Intravenous regional anesthesia (IVRA) or intravenous regional sympatholysis (IVRS) to an isolated extremity blocked with a tourniquet (level 4 evidence). Regional administration of IV guanethidine, bretylium, or reserpine depletes noradrenaline in the postganglionic axon. – Epidural spinal cord stimulation (level 4 evidence). May be effective for pain control in certain patients; does not improve return of function. – Chemical neurolysis or radiofrequency neuroablation; lacks strong evidence to support its

efficacy. – Surgical sympathectomy (level 4 evidence). Best results if within 12 months between injury and intervention. However, there is limited evidence on efficacy and long-term pain relief. • Physical therapy and occupational therapy are important in trying to restore and maintain function and range of motion (level 4 evidence). • Cognitive-behavioral therapy (CBT) together with physical therapy revealed beneficial effects in CRPS patients. • Biofeedback technology provides a patient with visual and/or auditory feedback regarding physiologic functions including muscle tension levels, perspiration, extremity temperature, and brain wave pattern. It teaches patients how to alter these functions through a variety of relaxation techniques, including progressive muscle relaxation, imagery, diaphragmatic breathing, and autogenic techniques. • Mind-body medicine: Mirror therapy provided pain reduction in a case series of CRPS Type I.

FOLLOW-UP • CRPS patients still have significantly higher levels of pain and dysfunction at 5 years after injury compared to reference patients with similar precipitating injuries who did not develop CPRS (5). • Up to 33% of patients may reach full recovery when examined at 5 years. • Factors that may contribute to poorest outcome include an affected upper extremity and the inciting event being other than a fracture.

REFERENCES

1. ruehl S. An update on the pathophysiology of complex regional pain syndrome. Anesthesiology. 2010;113(3):713–725. 2. arden RN, Bruehl S, Stanton-Hicks M, et al. Proposed new diagnostic criteria for complex regional pain syndrome. Pain Med. 2007;8(4):326–331. 3. Hsu ES. Practical management of complex regional pain syndrome. Am J Ther. 2009;16(2):147–154. 4. Singh G, et al. The value of interdisciplinary pain management in complex regional pain syndrome type I: A prospective outcome study. Pain Physician. 2004;7(2):203–209. de Mos Marissa, et al. Outcome of the complex regional pain syndrome. Clin J Pain. 2009;25(7):590–597. www.ninds.nih.gov • www.worksafebc.com

See Also (Topic, Algorithm, Electronic Media Element) • Complex regional pain syndrome II (CPRS II) • Assessment of acute pain

CODES

ICD9

• 337.20 • 337.21 Reflex sympathetic dystrophy of the upper limb • 337.22 Reflex sympathetic dystrophy of the lower limb ICD10

• G90.50 Complex regional pain syndrome I, unspecified • G90.511 Complex regional pain syndrome I of right upper limb • G90.512 Complex regional pain syndrome I of left upper limb

CLINICAL PEARLS

• The exact pathophysiologic mechanisms of CRPS are not entirely clear but are likely multifactorial in nature and linked to peripheral and central sensitization. • Other compounding factors in CRPS Type I may involve genetic factors, inflammation, altered sympathetic and catecholaminergic function, reduced representation of affected limb in the somatosensory cortex, and psychophysiologic interactions. • There is no gold standard for the diagnosis of CRPS Type I; currently it is based on clinical presentation, physical examination, and the aid of available tests. • A multidisciplinary approach in CRPS Type I must involve timely diagnosis, pain management, physical and occupational therapy, functional restoration, and psychosocial therapy. • Interventional pain management in CRPS Type I may consist of sympathetic blockade, a trial and evaluation for implantation of electrodes for spinal cord stimulation, and deep brain stimulation (neuromodulation).

COMPLEX REGIONAL PAIN SYNDROME (CRPS) TYPE II Farooq A. Qureshi, MD Eric S. Hsu, MD

BASICS DESCRIPTION

• Formerly known as causalgia, complex regional pain syndrome (CRPS Type II) is a chronic neuropathic pain condition characterized by the following: – A trauma or injury to an extremity – Nerve injury to the extremity, that is usually distal to the initial injury – Autonomic nervous system (ANS) dysfunction that can lead to allodynia, hyperalgesia, and trophic changes (skin color, temperature, hair and nail growth, and abnormal sweating) • It differs from CRPS Type I only in that there needs to be a definable nerve injury for CRPS Type II. EPIDEMIOLOGY Prevalence

• CRPS Type I develops more often than CRPS Type II (1). • Following peripheral nerve injury: ranges from 2–14% (mean 4%). • Following military nerve root injuries: – Men < 34 years: 10–15% – Men > 34 years: 47% Prevalence

• Approximately 4 per 100,000 persons • CRPS Type II usually occurs in one extremity • Male/female ratio of 1:3

ETIOLOGY/RISK FACTORS

May develop after any nerve injury including traumatic injury, amputation, surgery, and regional anesthesia PHYSIOLOGY/PATHOPHYSIOLOGY

• The mechanism of disease is multifactorial and includes the following (2): – Altered cutaneous innervations – Peripheral and central sensitization – Inflammation – Altered somatosensory representation in the brain – Altered sympathetic and catecholaminergic function – Genetic factors

– Psychophysiological interactions • Pathogenesis. The inciting injury leads to decreased C-fiber and A delta-fiber density at the site of injury. Primary afferent fibers in the injured area release several neuropeptides that increase background firing of nociceptive stimuli, and decrease the firing threshold for thermal and mechanical stimuli. Increased local and systemic levels of proinflammatory cytokines such as Tumor Necrosis Factor (TNF)-α, interleukin-1β, interleukin-2, and interleukin-6 are seen. Additionally, decreased systemic levels of the anti-inflammatory cytokine interleukin-10 also occur. Persistent noxious input leads to central sensitization involving N-Methyl-D-Aspartate (NMDA) receptors. • Sympathetically mediated pain (SMP). A coupling between the sympathetic noradrenergic neurons and primary afferents in the periphery of the body may occur at the site or along the lesioned nerve. Noradrenaline, released by the sympathetic nerve fibers, may activate and/or sensitize the afferent neurons and lead to SMP. Alternative coupling of sympathetic neurons to non-nociceptive afferent (e.g., mechanical and temperature) neurons may contribute to the mechanical or cold allodynia in CRPS Type II. • Sympathetically independent pain: The later stages of the syndrome are not responsive to sympathetic blockade. • Genetics. Studies suggest that there may be an association with the angiotensin-converting enzyme gene (non-major histocompatibilitycomplex (MHC) axis) as well as the HLA loci A3, B7, DQ1(06), DR2 (15), and DR13. • Psychology. The widely proposed myth “CRPS personality” does not appear to be substantiated by current studies. No differences in psychological patterns were found in those patients with radius fracture who developed CRPS Type II in comparison to patients who recovered without developing CRPS.

PREVENTATIVE MEASURES

Regional anesthesia and nerve blocks may minimize flare-ups in patients with a prior history of CRPS Type II who are scheduled for surgery on the affected extremity. Placement should occur prior to surgery or in the immediate postoperative period whenever SMP is a prominent feature.

PREOPERATIVE ASSESSMENT • International Association for the Study of Pain (IASP) Diagnostic Criteria for CRPS Type II (1995): – The presence of continuing pain, allodynia, or hyperalgesia after a nerve injury, not necessarily limited to the distribution of the injured nerve with which the pain is disproportionate to any inciting event. – Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain. – The diagnosis is excluded by the existence of any other condition that would account for the degree of pain and dysfunction. – CRPS Type II is diagnosed when there is identifiable nerve injury. • Diagnosis is based on history and physical exam findings. There is no gold standard procedure or test to confirm CRPS. Some useful tests that aid in diagnosis include the

following: – Electromyelogram and nerve conduction study may help to confirm the diagnosis of any definite nerve injury that complements the history in CRPS Type II. – Three-phase bone scintigraphy that demonstrates pathologic uptake in the metacarpophalangeal or metacarpal bones is highly sensitive and specific, but changes are not seen until the later stages. – Quantitative sensory testing is a standardized psychophysical testing of thermal and thermal pain thresholds and vibratory thresholds help to assess the function of large fiber, myelinated small fiber, and unmyelinated small afferent fibers. – Autonomic function testing includes infrared thermometry, laser Doppler flowmetry, infrared thermography, and a quantitative sudomotor axon reflex test.

DIFFERENTIAL DIAGNOSIS

• Post-traumatic neuralgia • Diabetic and other small fiber neuropathies; entrapment neuropathy • Thrombophlebitis • Deep vein thrombosis • Thoracic outlet syndrome • Vascular insufficiency • Infection such as cellulitis • Neuroma formation • Syringomyelia

TREATMENT • Should be multidisciplinary and aimed at providing both pain relief and functional restoration and rehabilitation. These include pharmacological, interventional, neuromodulation, rehabilitation, and alternative therapies (3). • Pharmacologic therapies are empiric and target the predominantly neuropathic symptoms. Randomized controlled trials are lacking. – Tricyclic antidepressants (TCA): First-line agents. Although there is no good outcome evidence, they remain the best-studied group of pharmacological agents in neuropathic pain. All TCAs have similar side effects: Sedation, anticholinergic effect, and should be cautiously used in patients with a known history of arrhythmias. Amitriptyline 10–75 mg PO QD; nortriptyline 10–75 mg PO QD; desipramine 10–75 mg PO QD – Serotonin–norepinephrine reuptake inhibitors (SNRI): First-line agents. Controlled studies are lacking, but they are approved for painful diabetic neuropathy and fibromyalgia. Duloxetine 30–120 mg PO QD – Anticonvulsants: Although they are off-label for CRPS, they are considered first-line agents. Side effects include somnolence, dizziness, and peripheral edema. Gabapentin 900–3600 mg/day divided into TID dosing; pregabalin 150–600 mg/ day divided into BID or TID dosing (4). – NSAIDS: Second-line agents and have not been extensively studied, but may help with inflammation and edema.

– Corticosteroids: Oral prednisolone 10 mg TID has been studied in the acute (<13 weeks) stage of CRPS. – Opioids are effective in postoperative and cancer pain. The use of opioids in neuropathic pain revealed efficacy when compared to placebo. There are no long-term studies on the efficacy of opioids for CRPS. – Gamma-aminobutyric acid (GABAB) agonists: Intrathecal baclofen up to 450 μg/day has

been used for treatment of dystonia associated with CRPS. – Bisphosphonates: Clodronate 300 mg IV QD or alendronate 7.5 mg IV QD may improve pain, swelling, and range of movement in acute CRPS. – Topical agents: Second-line and off-label use in CRPS. Clonidine patch for localized area of hyperalgesia and pain Lidocaine 5% patch to affected area 12 hours on/12 hours off. Diclofenac 1.3% patch to affected area BID Capsaicin 0.075% cream QID • Interventional therapies include peripheral, neuraxial, and sympathetic nerve blocks (5). – Peripheral nerve blocks can be performed for each specific nerve presumed to be involved in CRPS Type II over the upper or lower extremity. The brachial plexus block may be considered if more than one peripheral nerve is suspected. No plexus block can be recommended for CRPS Type II involving the lower extremity. – Epidural techniques. Continuous epidural infusion with local anesthetics and opioids in coordination with intensive physical and occupational therapy and functional rehabilitation may be performed as an inpatient. Epidural clonidine can provide greater pain reduction at higher dosages (700 μg) compared to lower dosages (300 μg) in CRPS; however, this may be associated with significant side effects (sedation, hypotension). Epidural steroid injections have not been studied in the treatment of CRPS Type II. – Sympathetic nerve blocks such as a stellate ganglion block or lumbar sympathetic block (level 4 evidence) can help to differentiate if pain has a strong SMP. Eighty-five percent of the patients report a positive acute effect, but fewer patients experience long-term relief. There is no definitive protocol for selecting candidates for stellate and lumbar sympathetic blockade. – IV regional anesthesia: Level 4 evidence. Use of IV bretylium or reserpine to deplete noradrenaline in the postganglionic axon to an isolated extremity blocked with a tourniquet. • Neuromodulation techniques may be considered and utilized when patients reach the plateau in responding to nerve blocks; involve advanced interventional techniques. – Spinal cord stimulation has been shown to significantly reduce pain levels as well as improve functional status and quality of life. – Peripheral nerve stimulation: Especially advantageous for CRPS Type II as there has been definite nerve injury. – Surgical sympathectomy (level 4): Best results if performed within the first year of injury. Limited evidence on efficacy. • Rehabilitation methods include (6) – Physical therapy and occupational therapy are important in trying to improve function and range of motion (level 4).

FOLLOW-UP Outcome studies:

• CRPS patients have significantly higher symptoms and signs of pain and injury than reference patients with the same precipitating injury who did not develop CPRS at 5 years (7). • Thirty-three percent of patients reach full recovery when examined at 5 years. • Patients in the poorest outcome group often had their upper extremity affected, inciting event other than a fracture, and cold extremities.

REFERENCES

1. eldman PH, Reynen HM, Goris RJ. Signs and symptoms of reflex sympathetic dystrophy: Prospective study of 829 patients. Lancet. 1993;342:1012–1016. 2. Bruehl S. An update on the pathophysiology of complex regional pain syndrome. Anesthesiology. 2010;113(3):713–725. 3. Hsu ES. Practical management of complex regional pain syndrome. Am J Therapeutics. 2009;16(2):147–154. 4. Rowbotham MC. Pharmacologic management of complex regional pain syndrome. Clin J Pain. 2006;22:425–429. 5. Nelson DV, Brett RS. Interventional therapies in the management of complex regional pain syndrome. Clin J Pain. 2006;22:438–442. 6. Singh G, et al. The value of interdisciplinary pain management in complex regional pain syndrome type I: A prospective outcome study. Pain Physician. 2004;7(2):203–209. 7. de Mos Marissa, et al. Outcome of the complex regional pain syndrome. Clin J Pain. 2009;25(7):590–597.

ADDITIONAL READING • www.ninds.nih.gov • www.worksafebc.com

See Also (Topic, Algorithm, Electronic Media Element) • Complex regional pain syndrome (CRPS) Type I • Autonomic nervous system

CODES ICD9 • 354.4 Causalgia of upper limb • 355.71 Causalgia of lower limb ICD10

• G56.40 Causalgia of unspecified upper limb • G56.41 Causalgia of right upper limb • G56.42 Causalgia of left upper limb

CLINICAL PEARLS

• A definable injury of the peripheral nerve is required for the diagnosis of CRPS Type II in addition to the common symptoms and signs seen in CRPS Type I. • The exact pathophysiologic mechanisms of CRPS Type II are not entirely clear but are likely multifactorial in nature and linked to peripheral and central sensitization following nerve injury that leads to inflammation and sympathetic nervous system dysfunction. • There is no gold standard test except the documentation of nerve injury for diagnosis of CRPS Type II. Diagnosis criteria are based on clinical presentation, physical examination, and the aid of available tests. • Treatment of CRPS Type II should be immediate and focus toward restoration of full function of the affected extremity. This goal is best achieved by an interdisciplinary team involving pain management, physical and occupational therapy, and psychosocial support and therapy. • Interventional pain management in CRPS Type II may consist of sympathetic blockade, diagnostic and therapeutic peripheral nerve blocks, and a trial implant of electrodes for peripheral nerve stimulation and/or spinal cord stimulation as neuromodulation.

CONGENITAL DIAPHRAGMATIC HERNIA Ranu Jain, MD

BASICS DESCRIPTION

• Congenital diaphragmatic hernia (CDH) is a failure of a portion of the fetal diaphragm to fully develop. The defect allows abdominal contents to enter the thorax, often interfering with normal lung growth. • CDH can present as a neonatal life-threatening emergency.

EPIDEMIOLOGY Prevalence

Live births: ∼1:2000 to 1:5000 Prevalence

• More common in males • Left-sided CDH is more common • In an otherwise healthy neonate with CDH, the maternal risk of recurrence for future pregnancies is only 2%. Morbidity

Related to the degree of pulmonary hypoplasia and comorbidities (e.g., cardiac, spinal, etc) Mortality

• Ranges from 40% to 62% (decreased in otherwise healthy children). • Mortality has been correlated with the initial Alveolar-arterial oxygen difference, (A-a) gradient, after surgical repair. – <400 mm Hg = likely survival – 400–500 mm Hg = intermediate chances – >500 mm Hg = unlikely to survive • Those presenting later in childhood (Morgagni’s hernia), or even adulthood, have an extremely good outcome, with low or no mortality. ETIOLOGY/RISK FACTORS

• Cause remains unknown • There does appear to be a genetic link and an increased risk if a sibling or a parent had the condition. PHYSIOLOGY/PATHOPHYSIOLOGY

• CDH results from a failure of fusion of peripheral and central elements of the diaphragm. • Respiratory. Pulmonary hypoplasia occurs secondary to compression by abdominal contents.

There is an abnormal division of airways that results in a decreased number of bronchi, alveoli, and pulmonary arterial branches. Additionally, there is surfactant deficiency and premature muscularization of pulmonary vessels. Severity is related to the time during gestation when herniation occurred (usually during the 8th week). – Mechanical abnormalities result from the herniation of abdominal contents shifting into the mediastinum; causes the mediastinum to shift to the opposite side of the defect. – Circulating vasoactive mediators increase, as does the body’s sensitivity. This further worsens the pulmonary hypertension associated with CDH.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Reduction in the herniated viscera and closure of the diaphragmatic defect should be emergently performed following birth. However, surgical treatment can be delayed to stabilize infants with pulmonary hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). Preoperative stabilization with delayed repair has become the standard of care. • Physiologic considerations include hypoxemia, hypercarbia, acidemia, pulmonary hypertension and associated right-to-left shunting, possible pneumothorax, and malrotation. • Goals – Adequate gas exchange and prevention of worsening metabolic or respiratory acidosis while avoiding ventilator-associated lung injury. – Avoidance of aspiration – Adequate pain control – Maintain normothermia, volume status, and electrolyte balance.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Cyanosis • Tachycardia • Tachypnea, retractions, grunting, severe respiratory distress • A small subset of patients (∼5%) present primarily with bowel obstruction and minimal respiratory distress.

History

• Birth history • Prematurity • Weight • Pulmonary status: Oxygen requirements, intubation history. If intubated, note the ventilator settings and size of endotracheal tube. • Other congenital anomalies (cardiac abnormalities are present in ∼25% of cases) • History of blood product transfusions • Family history of congenital anomalies or malignant hyperthermia • History of extracorporeal membrane oxidation (ECMO)

Signs/Physical Exam

• Intrathoracic bowel sounds • Scaphoid abdomen, barrel-shaped chest • Auscultation of the lungs typically reveals poor air entry on the left (with a left posterolateral hernia), and shifting of cardiac sounds over the right chest. TREATMENT HISTORY

• Minimally invasive fetal surgeries have been attempted (e.g., tracheal balloon occlusion) to promote the growth of hypoplastic lung tissue, but it has not shown improved survival. • Ex utero intrapartum therapy (EXIT) procedures may be performed for severely hypoplastic lungs with very large CDH. • ECMO. Morbidity occurs secondary to anticoagulation and intracranial bleeding. Indications include – Estimated gestational age >35 weeks – Absence of intracranial hemorrhage – Absence of uncorrectable cyanotic congenital heart disease – Absence of uncorrectable associated anomalies – Parental consent • Nitric oxide can promote smooth muscle relaxation and short-term improvements in arterial oxygenation. Its use is controversial; it may be helpful in the initial stabilization, but does not reduce the need for ECMO or decrease mortality. • Permissive hypercapnia to a PaCO2 of 60 mm Hg may decrease ventilator support and barotrauma as well as dilate the pulmonary vasculature; in the setting of pulmonary hypoplasia, this can be beneficial. However, it remains controversial. • High frequency oscillatory ventilation (HFOV). May be utilized if conventional ventilation fails to reverse hypercapnia and hypoxemia. It avoids injury to the lung and preserves end expiratory lung volume without overdistension. MEDICATIONS

• Sedation and muscle relaxation are used in intubated patients to avoid ventilator dyssynchrony and decrease the release of catecholamines, which may increase pulmonary vascular resistance. • IV fluids and total parenteral nutrition (TPN) should be continued in the OR.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Amniocentesis and karyotyping for chromosomal abnormalities or low levels of alphafetoprotein. • Prenatal ultrasound can reveal polyhydramnios; the heart may be shifted to the opposite side of the hernia, and intestinal loops may be seen in the chest. • Chest radiograph. Typical findings in a left-sided posterolateral CDH include air-filled or fluid-filled loops of the bowel in the left hemithorax and shift of the cardiac silhouette to the right, with or without pneumothorax. • Echocardiogram to assess myocardial function and determine whether the left ventricular mass is significantly decreased.

• Ultrasound of the brain to evaluate for intraventricular bleeding, hypoxic–ischemic changes, and major intracranial anomalies.

CONCOMITANT ORGAN DYSFUNCTION

• CNS: Neural tube defects or hydrocephalus • Craniofacial, extremity, or spinal abnormalities • Genitourinary anomalies (6–8%)

CIRCUMSTANCES TO DELAY/CONDITIONS

Surgical treatment can be delayed to stabilize pulmonary hypoplasia and PPHN. CLASSIFICATIONS

• The Bochdalek hernia, also known as a posterolateral diaphragmatic hernia, can occur on the left or right. It accounts for >95% of cases. • Morgagni’s hernia, also known as a retrosternal or parasternal hernia can occur through this right, anterior defect (known as the foramen of Morgagni). Infants may be asymptomatic; however, repair is still recommended to avoid the risk of a strangulated intestine. Accounts for ∼2% of cases. • Diaphragmatic eventration describes cranial displacement of part, or all, of an otherwise intact diaphragm into the chest cavity. This rare type of CDH occurs due to incomplete muscularization of the diaphragm or failure of phrenic nerve innervation, and can be found unilaterally or bilaterally. Minor forms of diaphragm eventration are asymptomatic; however, severe cases will present with respiratory distress similar to Bochdalek hernia.

TREATMENT PREOPERATIVE PREPARATION Premedications

Patient may be intubated, sedated, and/or paralyzed. Special Concerns for Informed Consent

• Postoperative intubation may be needed. • Postoperative ECMO support may be needed. • Epidural for postoperative analgesia may be needed.

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia • Epidural for postoperative pain control

Monitors

• Standard ASA monitors • Pulse oximeter probes at preductal (right-hand) and postductal (either foot) sites are helpful for assessing right-to-left shunt at the ductus arteriosus level. In PPHN, the preductal PaO2

is higher. • Arterial line should be placed for frequent blood gas measurements.

Induction/Airway Management

• Patients are considered an aspiration risk. They should have their stomach suctioned before induction, followed by a rapid sequence with succinylcholine or rocuronium; alternatively, an awake intubation may be appropriate. • Prior to the start of surgery, patients should have adequate IV access and blood products available in order to treat possible intraoperative blood loss. • An epidural can be placed after intubation. Transcaudal, lumbar, or thoracic sites are all options to provide chest wall/pleural or abdominal analgesia.

Maintenance

• Opioids and/or volatile anesthetics with neuromuscular blockade. Nitrous oxide is avoided because it can diffuse in the viscera and exaggerate lung compression. • Ventilator. Rates of 30–60 breaths/minute while maintaining the PIP <25 cm H2O to

minimize barotraumas. – A PaO2 >50 mm Hg can provide for adequate oxygen delivery at the tissue level. Higher concentrations may require increased ventilator support and barotrauma. – A lower FI02 is preferred to avoid retinopathy of prematurity. Optimal FI02 maintains the preductal SpO2 between 95% and 100%.

• Fluids. Active warming of the patient, IV fluids, and/or blood products should be done to avoid hypothermia. – Dextrose-containing fluids are preferred due to the decreased glycogen stores in the neonate. – The amount of insensible losses will depend on the size of the defect. – Blood loss is typically minimal. • Hematocrit. Should be maintained between 30% and 35%; fetal hemoglobin has an increased affinity to oxygen and a decreased sensitivity to 2,3-DPG that can exacerbate cellular hypoxia. • Chest tube drainage is necessary when a tension pneumothorax is present.

Extubation/Emergence

• Postoperative intubation is needed in infants with increased airway pressures and/or pulmonary hypertension. • Pain control with IV narcotics or epidural

FOLLOW-UP BED ACUITY

NICU or PICU

MEDICATIONS/LAB STUDIES/CONSULTS

• Blood gas analysis to assess oxygenation and ventilation, as well as possible postoperative acidosis. • CBC to evaluate hematocrit after surgical blood loss and intraoperative volume shifts. • Ventilator settings: Low peak pressures to avoid injury to the normal lung. • Pneumothorax on the unaffected side should be suspected if the infant is hypotensive and hypoxic.

COMPLICATIONS

• Hypoventilation • Pneumothorax • Metabolic acidosis • Hypothermia • All the above conditions could lead to right-to-left shunting either through the ductus arteriosus or an abnormal shunt (e.g., ASD, etc).

REFERENCES

1. de buys Roessingh AS, Dinh-Xuan AT. Congenital diaphragmatic hernia: Current status and review of the literature. Eur J Pediatr. 2009;168(4):393–406. 2. Langer JC. Congenital diaphragmatic hernia. Chest Surg Clin N Am. 1998;8(2):295–314. 3. Moya FR, Lally KP. Evidence-based management of infants with congenital diaphragmatic hernia. Semin Perinatol. 2005;29(2):112–117. 4. Finer NN, Tierney A, Etches PC, et al. Congenital diaphragmatic hernia: Developing a protocolized approach. J Pediatr Surg. 1998;33(9):1331–1337. See Also (Topic, Algorithm, Electronic Media Element) • Retinopathy of prematurity • Pneumothorax

CODES ICD9 756.6 Anomalies of diaphragm ICD10 Q79.0 Congenital diaphragmatic hernia

CLINICAL PEARLS

• CHD presents as a life-threatening emergency; nonetheless, respiratory and cardiac stabilization should be ensured prior to surgical correction. This may entail the use of ECMO and/or nitric oxide. ECMO is recommended for neonates with reversible respiratory failure. • Prognosis is related to the degree of hypoplasia and the pulmonary muscular abnormalities,

which result in decreased lung compliance and risk of hypoventilation.

CONGESTIVE HEART FAILURE John F. Coleman, MD Wei Dong Gao, MD, PhD

BASICS DESCRIPTION

• Congestive heart failure (CHF) can result from a syndrome of ventricular or valvular function abnormalities, as well as improper neurohormonal regulation, leading to inadequate blood flow and pressure to meet the body’s metabolic demands (1). • CHF presents in one of three ways: – Tissue hypoperfusion and hypoxia; fatigue, dyspnea, decreased exercise tolerance – Fluid retention – Coincidentally during the evaluation of another disorder EPIDEMIOLOGY Prevalence

Age group, per 1,000 (2): • 65–74 years: 9.2 male, 4.7 female • 75–84 years: 22.3 male, 14.8 female • 85 years and older: 41.9 male, 32.7 female Prevalence

Adults 20 and older: 5,800,000 in the US (3,100,000 males, 2,700,000 females) (2)

Morbidity

• In 2006, accounted for 1,106,000 hospital discharges in the US (3,4). • Perioperative all-cause 30-day readmission is 17.1% versus 10.8% for coronary artery disease (CAD).

Mortality

• One-year mortality rate: 1 in 5 (3,4) • Any-mention death rate: 98.2 per 100,000 deaths; 103.7 for white males, 105.9 for black males, 80.3 for white females, 84.4 for black females • Perioperative all-cause mortality: 8% versus 3.1% for CAD.

ETIOLOGY/RISK FACTORS

• Cardiac: Hypertension (HTN), myocardial infarction, CAD, valvular disease (1,5) • Metabolic: Diabetes mellitus, dyslipidemia • Demographics: Family history, age • Lifestyle: Obesity and tobacco use • Medications: Toxins (e.g., chemotherapy)

PHYSIOLOGY/PATHOPHYSIOLOGY

• HF is a progressive disorder that can affect systolic and diastolic function, independently or simultaneously (6,7). • Systolic dysfunction is encompassed by a decline in the pumping capacity of the left ventricle (LV) after an index event. This event causes a loss of myocytes and/or a decreased ability of the myocytes to generate force. • Diastolic dysfunction is the abnormal filling and relaxation of the LV resulting from decreased compliance or impaired relaxation. LV relaxation is an energy-requiring process and will be negatively affected by ischemia. When the LV has normal ejection fraction (EF) and there are signs and symptoms of HF, it is termed “normal ejection fraction heart failure” • Compensatory mechanisms maintain cardiac output. These include the following: – Modifications of the adrenergic system and retention of salt and water. – Activation of vasodilatory molecules to offset vasoconstriction/increased afterload by the adrenergic system. – Neurohumoral and cytokine system activation causing LV remodeling and CHF progression; involves changes in myocyte biology, myocyte loss, matrix degradation, and alterations in LV geometry.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintain cardiac output and prevent myocardial ischemia by avoiding acute changes in right ventricle (RV) and LV preload and afterload, heart rate, and myocardial oxygen balance. Mild HTN is better tolerated than hypotension. • Hemodynamic consequences of HF include decreased cardiac output, increased LV enddiastolic pressure (EDP), peripheral vasoconstriction, retention of sodium and water, and decreased oxygen delivery.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Dyspnea, paroxysmal nocturnal dyspnea, orthopnea, cough • Chest pain • Exercise intolerance, fatigue, weakness • Anorexia and nausea • Nocturia • Cognitive dysfunction

History

• Baseline functionality (7,8) • History of CAD, cardiac surgery, abnormal blood pressure; NYHA or ACC/AHA classification. • Diabetes and blood glucose levels • Use of tobacco, alcohol, and illicit drugs. • Pacemaker and internal cardiac defibrillator (ICD) settings and interrogation.

Signs/Physical Exam

• Vital signs, height, and weight (8) • Tachypnea, rales, pleural effusions, cyanosis • Resting tachycardia and S3 heart sound; jugular venous distension • Hepatomegaly, ascites, peripheral/dependent edema

MEDICATIONS

• Beta-blockers counteract the neurohumoral effects of HF to decreased myocardial oxygen consumption, while improving ventricular systolic function and reversing ventricular remodeling (1,9). • Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) prevent and decrease ventricular remodeling; may cause hyperkalemia. Also have been associated with refractory hypotension during general anesthesia. • Diuretics decrease preload. Should be held in the immediate preoperative period. • Digoxin offers rate and rhythm control and positive inotropy in those patients who remain symptomatic on beta-blockers, ACE inhibitors, and diuretics. • Vasodilators decrease afterload and wall tension. • Statins may offer some benefit to patients with CAD in that they have pleiotropic (nonlipid lowering) effects of decreased inflammation and stabilization of atheromatous plaques. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, BUN, and creatinine (8) • CBC • TSH, liver function • Chest x-ray (CXR) (cardiomegaly, pulmonary edema, pneumonia) • ECG (myocardial infarction and ischemia, left ventricular hypertrophy (LVH), conduction abnormalities or dysrhythmias) • Echocardiography (EF%, LV structure/function, valvular pathology) • Digoxin level • Brain natriuretic peptide (BNP) (for new diagnosis to risk stratify only) • Pacemaker and ICD interrogation • Cardiac catheterization, noninvasive testing

CONCOMITANT ORGAN DYSFUNCTION

• Neurological: Cerebrovascular disease, stroke and transient ischemic attacks (TIAs) • Cardiovascular: HTN, arrhythmias, peripheral vascular disease, anemia • Pulmonary: COPD • Metabolic: Diabetes mellitus, hyperlipidemia

CIRCUMSTANCES TO DELAY/CONDITIONS • Decompensated HF • Myocardial ischemia • Unstable arrhythmias

CLASSIFICATIONS

• New York Heart Association (NYHA) – I – not limited by symptoms – II – somewhat limited by dyspnea – III – dyspnea during a mild workload – IV – dyspnea at rest or little exertion • American College of Cardiology/American Heart Association (ACC/AHA) – A – high risk but without symptoms – B – structural heart disease without signs/symptoms – C – prior or current symptoms – D – refractory HF requiring specialized interventions

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis should be titrated cautiously; monitor for hypoxia. • Beta-blockers should be continued perioperatively. Randomized controlled trials have shown improved outcome in high-risk cardiac patients by preventing arrhythmias and ischemia. INTRAOPERATIVE CARE Choice of Anesthesia

All types have been used successfully. Both general and neuraxial techniques result in sympatholysis in patients with high compensatory sympathetic tone; can result in profound hypotension that should be anticipated and treated aggressively. Monitors

• ASA standard monitors • Invasive monitoring is dependent on the severity of disease, surgical procedure, and emergency surgery. • Arterial lines can aid with beat-to-beat blood pressure monitoring and frequent lab draws. Worsening Alveolar-arterial (A-a) gradient or a-A ratio as well as metabolic acidosis/base excess can indicate worsening pulmonary edema, fluid overload, and/or myocardial pump or valvular dysfunction. • Central venous monitoring can aid with assessing ventricular filling and fluid status. A pulmonary artery catheter can provide additional information of mixed venous oxygen saturation (an indicator of worsening cardiac output), systemic vascular resistance (SVR), and LVEDP; can guide and assess inotropic, vasodilator, and diuretic therapy intraoperatively and postoperatively. • Transesophageal echocardiography (TEE) can aid with monitoring ventricular filling, ventricular wall motion, valve function, and EF. Limited by clinical expertise, availability, and intraoperative use.

Induction/Airway Management

• Both IV and inhalational agents can be utilized for induction, and should be titrated carefully. • Propofol causes vasodilation and hypotension; consider lower doses, and more time for onset of action. • Etomidate has favorable hemodynamic effects but can cause some decrease in blood pressure in patients with ventricular dysfunction or HF. • Ketamine can be useful in the setting of poor ventricular function (EF <30%) due to its sympathomimetic effects. It also has the potential to cause negative inotropic effects in the patient with ventricular dysfunction or cardiomyopathy. • Opioids, lidocaine, and other IV anesthetics can blunt the sympathetic stimulation with laryngoscopy and intubation to prevent tachycardia and HTN. • High-dose opioids in combination with other IV anesthetics cause a dose-dependent cardiac depression likely due to blunting of the already elevated sympathetic tone.

Maintenance

• Both inhalational and/or IV balanced anesthesia techniques can be utilized; they include inhaled volatile and nitrous oxide, opioid, and neuromuscular blockers. Sympatholysis can be accentuated and compounded in patients with a high sympathetic tone, such as in HF patients. Therefore, it is important to consider smaller doses and to titrate to desired effects. • Positive pressure ventilation (PPV) and positive end-expiratory pressure (PEEP) may decrease pulmonary congestion and improve arterial oxygenation (decrease atelectasis and shunting of alveolar–capillary units). • Fluids should be carefully titrated to optimize preload (Frank–Starling curve) while avoiding RV and LV overload and pulmonary congestion. • Since HF patients have down regulation of B1 receptors, a combination of inotropic agents with different mechanism of action may sometimes be needed (i.e., epinephrine + milrinone).

Extubation/Emergence

• Standard extubation criteria apply; however, patients may be less capable of meeting them. • Prevent and immediately treat tachycardia, hypotension/HTN, and increased/decreased contractility if present. Hypotension can be a sign of myocardial ischemia and/or worsening HF. • Supplemental oxygen should be administered. • Treat shivering and hypothermia.

FOLLOW-UP BED ACUITY

• Intensive care unit (ICU) for patients with acute or worsening HF, invasive monitoring, or vasopressors and inotropic support. • Patients requiring furosemide and/or vasodilators (i.e., nitroglycerine) for pulmonary edema should be observed in an acute setting.

• Consider supplemental oxygen • If medication treatment fails, consideration should be made for a mechanical ventricular assist device, biventricular pacemaker for resynchronization therapy, coronary artery bypass or surgical ventricular remodeling, or even heart transplantation may be considered (9).

COMPLICATIONS

Worsening HF/acute exacerbations can be a sign of myocardial ischemia, arrhythmias, electrolyte disturbances, anemia, and hypotension (10).

REFERENCES

1. roban L, Butterworth J. Perioperative management of chronic heart failure. Anesth Analg. 2006;103:557–575.

2. Heart Disease and Stroke Statistics 2010 Update, American Heart Association. Fleisher LA. Implications of preoperative heart failure. Anesthesiology. 2008;108:551–552. 3. ammill BG, et al. Impact of heart failure on patients undergoing major noncardiac surgery. Anesthesiology. 2008;108:559–567. 4. Schocken DD, et al. Prevention of heart failure. Circulation. 2008;117:2544–2565. 5. Mann DL, et al. Mechanisms and models in heart failure: The biomechanical model and beyond. Circulation. 2005;111:2837–2849. 6. Mancini D, Burkhoff D. Mechanical device-based methods of managing and treating heart failure. Circulation. 2005;112:438–448. 7. Wojciechowski P. Perioperative optimization of the heart failure patient. Int Anesthesiol Clin. 2009;47(4):121–135. 8. Jessup M, et al. 2009 Focused update: ACCF/AHAe guidelines for the diagnosis and management of heart failure in adults. Circulation. 2009;119:1977–2016. 9. Fonarow GC, Abraham WT, Albert NM, et al. Factors identified as precipitating hospital admissions for heart failure and clinical outcomes: Findings from OPTIMIZE-HF. Arch Intern Med. 2008;168:847.

ADDITIONAL READING

• ACC/AHA guidelines for the diagnosis and management of heart failure in adults. • Noninvasive testing as recommended by the ACC/AHA guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery.

See Also (Topic, Algorithm, Electronic Media Element) • Coronary artery disease • Mixed venous oxygen saturation • High-output cardiac failure • Afterload • Preload • Left ventricular end diastolic pressure • Lusitropy

CODES ICD9

428.0 Congestive heart failure, unspecified ICD10 I50.9 Heart failure, unspecified

CLINICAL PEARLS

• Assess the severity of HF and other organ involvement in order to plan appropriate anesthetic technique. • Elective surgery should be postponed in patients with acutely decompensated HF. • Patients with CHF have a high risk for perioperative morbidity and mortality. • The primary goal of anesthesia care for patients with HF is maintaining cardiac output by optimizing both preload and afterload, preventing cardiac ischemia, and avoiding cardiac dysrhythmias throughout the perioperative period.

CONTEXT-SENSITIVE HALF-TIME Elizabeth Rebello, MD

BASICS DESCRIPTION

• Context-sensitive half-time is a pharmacokinetic parameter that differs from elimination half-life. • It is defined as the time required for the plasma drug concentration to decline by 50% after terminating an infusion. It takes into account: – Multicompartment systems – The concepts of distribution as well as elimination – Duration of infusion • The concept of context-sensitive half-time has improved the understanding of the pharmacokinetic behavior of anesthetic drugs after constant infusion. PHYSIOLOGY PRINCIPLES

• Until computer simulations proved otherwise, the elimination half-life of a drug, or the time necessary for the concentration in the plasma to decrease by one-half of its original value, was often used to describe the duration of a drug’s clinical effect (1). • One-compartment pharmacokinetic model. The elimination half-life provides a useful and suitable description of the rate of drug disposition on a one-compartment model. It reflects metabolic capacity. However, it is of limited value in depicting the pharmacokinetics of drugs with a multicompartment model (1). • Multicompartment pharmacokinetic model. The context-sensitive half-time provides a useful and suitable description of the rate of drug disposition in a multicompartment model. Hence, it is useful in describing IV anesthetics and analgesics. – Gradients. The concentration gradient between the compartments is the driving force upon which plasma drug concentration differs in extent and direction over time. – Continuous infusion. When a drug with a multi-compartment pharmacokinetic model is given via a steady-state infusion, central compartment drug levels: Immediately increase Decline after a short administration interval because of redistribution into peripheral compartments Gradually fall after equilibrium has been reached with peripheral compartments, secondary to drug metabolism or elimination (2,5). This assumes that the infusion does not exceed the body’s metabolic/elimination rate. – Discontinuation of infusion. If equilibrium between the compartments has occurred, the plasma concentration will decline over time from metabolism and elimination. Eventually, the drug will move from the peripheral compartment back into the plasma; by doing so, it maintains the plasma concentration of the drug and extends its pharmacological effect (2,3).

If equilibrium between the central and peripheral compartments has not occurred at the time that the infusion is stopped, drug in the plasma will continue to redistribute as well as be metabolized and eliminated. Eventually, the gradient will favor movement from the peripheral compartment to the plasma (extends pharmacologic effect). • Context-sensitive half-time is – A pharmacokinetic parameter that is independent from elimination half-life (2). For a multicompartment pharmacokinetic model, it is a more suitable descriptor of the rate of drug disposition than the elimination half-life.

FIGURE 1. Context-sensitive half-times as a function of infusion duration. (Reproduced with permission from Hughes MA,

Glass PSA, Jacobs JR. Context–sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 1992;76:334–341.)

– A function of the duration of the drug administration (Figure 1); it increases as duration increases. – Not a constant number; the relative effect of distributive processes on the plasma concentration fluctuates over time and differs for each drug – A tool by which different drugs may be compared and can aid with selecting an appropriate choice for an infusion (6).

ANATOMY

• Central compartment: Plasma • Peripheral compartment: Muscle, fat, etc.

DISEASE/PATHOPHYSIOLOGY

Concurrent disease states may affect the context-sensitive half-time and recovery time PERIOPERATIVE RELEVANCE

• The concept of context-sensitive half-time has increased the understanding of appropriate drug selection for an infusion and has developed the practice of total intravenous anesthesia (TIVA) as a standard type of anesthesia (5). Context-sensitive half-times are now defined in drug development literature of IV analgesics and anesthetics to demonstrate that a drug may be used as an infusion (4,5). – Propofol. The context-sensitive half-time is not significantly prolonged even at a long duration. This demonstrates one of the characteristics of propofol that makes it a suitable drug for continuous infusion. – Fentanyl. The context-sensitive half-time is significantly prolonged after 2 hours. Less suitable for a constant infusion at long duration. – Sufentanil. The context-sensitive half-time is not prolonged at a long duration. Suitable for a continuous infusion. – Alfentanil. Longer context-sensitive half-time as compared to sufentanil. – Remifentanil. Context-sensitive half-time is independent of infusion duration and very suitable for constant infusion. – Midazolam. Longer context-sensitive half-time than propofol. – Dexmedetomidine. Short context-sensitive half-time with infusions of short durations; increases significantly with infusions of long (>8 hour) duration (7). – Ketamine. Moderately short context-sensitive half-time, however, can become greater than propofol over time with increased infusion duration. • Limitations. The context-sensitive half-time may not always be a clinically relevant parameter (2,8): – Inhaled anesthetics: Desflurane, sevoflurane, isoflurane, and enflurane have small contextsensitive half-times (<5 minutes) and do not increase significantly with increasing duration (8). – Does not directly describe how long it will take a patient to recover from IV anesthetics; the site of action of IV anesthetics is in the brain, not in the plasma (6). • Recovery describes awakening and being capable of maintaining spontaneous ventilation. – Dependent on factors such as the discrepancy between the plasma drug concentration at the termination of an infusion and the plasma concentration below which awakening occurs (9). – The effect-site decrement time, or the time required for any specified decrement in effectsite concentration, may be a better predictor of recovery (9). – May be affected by drug interactions and concurrent disease states (10). • Intravenous anesthetics affect SSEPs to a lesser extent than volatile anesthetics. Infusions of various drugs and combinations of drugs are commonly utilized with or without volatile agents/nitrous oxide. They include: Propofol, etomidate, barbiturates, ketamine, opioids, benzodiazepines, and other drugs (clonidine, dexmedetomidine, droperidol). Choice is often dictated by hemodynamic parameters, side-effects, and context-sensitive half-time.

REFERENCES

1. Shafer SL, Varvel JR. Pharmacokinetics, pharmacodynamics, and rational opiod selection. Anesthesiology. 1991;74:53–63. 2. Hughes MA, Glass PSA, Jacobs JR. Context –sensitive half-time in multi-compartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 1992;76:334– 341. 3. Keifer J, Glass P. Context-sensitive half-time and anesthesia: How does theory match reality? Curr Opin Anaesthesiol. 1999;12(4):443–448. 4. Bailey JM. Context-sensitive half-times. What are they and how valuable are they in anesthesiology? Clin Pharmacokinet. 2002;41(11):793–799.

5. Glass PSA, Half-time or half-life: What matters for recovery from intravenous anesthesia? Anesthesiology. 2010;112:1266–1269.

6. Schnider TW, Shafer SL. Evolving clinically useful predictors of recovery from intravenous anesthetics. Anesthesiology. 1995;83:902–905. 7. eeves JG, Glass SA, Lubarsky DA. Intravenous nonopioid anesthetics. In: Miller RD, ed. Miller’s Anesthesia, 6th ed. Philadelphia: Elsevier Churchill Livingstone, 2005;317–378. 8. Bailey JM. Context sensitive half-times and other decrement times of inhaled anesthetics. Anesth Analg. 1997;85:681–686. 9. Bailey JM. Technique for quantifying the duration of intravenous anesthetic effect. Anesthesiology. 1995;83:1095–1103. 10. Schrag S, Mohl U, Hirsch M, et al. Recovery from opiod anesthesia: The clinical implications of context-sensitive half-times. Anesth Analg. 1998;86:184–190. See Also (Topic, Algorithm, Electronic Media Element)

• Propofol infusion syndrome • Somatosensory evoked potentials/motor evoked potentials (SSEP/MEPs)

CLINICAL PEARLS

• Context-sensitive half-time is the time required for the plasma drug concentration to decline by 50% after terminating an infusion. • It takes into account the effects of distribution and metabolism on drug disposition. • The context-sensitive half-time has improved our understanding of the pharmacokinetics of anesthetics drugs after a continuous infusion. Additionally, it has complemented the basis for drug selection when administering an infusion and has encouraged the use of TIVA as a standard practice in anesthesia. • Context-sensitive half-time does not directly describe how long it will take a patient to recover from IV anesthetics.

CONTINUOUS POSITIVE AIRWAY PRESSURE Rachel Helle, DO Lydia A. Conlay, MD, PhD

BASICS DESCRIPTION

• Continuous positive airway pressure (CPAP) is a form of noninvasive positive pressure ventilation (NPPV). CPAP – Provides a constant level of pressure to the airway throughout the respiratory cycle. – Can be delivered via a nasal mask, nasal pillow, or full face mask with straps. – Does not require endotracheal intubation. – Levels are typically 5–12 cm H2O.

– Requires a conscious, cooperative patient, an adequately fitted facemask, and hemodynamic stability • CPAP is contraindicated in patients that: – Require endotracheal intubation – Are unable to adequately eliminate CO2 – Have acute facial trauma – Have impaired swallowing – Have gastrointestinal bleeding • It is most commonly utilized by patients in the outpatient setting with obstructive sleep apnea. For inpatients, it is utilized for chronic obstructive pulmonary disease (COPD) exacerbations or cardiogenic pulmonary edema. PHYSIOLOGY PRINCIPLES

• CPAP creates a back pressure within the airway to recruit fluid-filled or collapsed alveoli and increase effective lung inflation. In doing so, it – Increases the functional residual capacity (FRC). Initially, CPAP affects only functional alveoli, but with time will recruit unventilated alveoli. – Can improve oxygenation by optimizing V/Q matching; improves ventilation to previously atelectatic alveoli. – Increases lung compliance by allowing alveoli to remain open. – Reduces the work of breathing by forcing air into the lungs so inspiratory muscles require less effort to generate negative pressure. – Does not aid with CO2 elimination. • CPAP is applied to a spontaneously breathing patient; it cannot provide mandatory or assisted breaths. Patients determine their own respiratory rate, inspiratory time, and tidal volume; it is effort independent. It requires a tight-fitting mask with no air leaks in order to function appropriately. • BiPAP (bi-level positive airway pressure) is similar to CPAP with two levels of pressure: A

higher pressure for inspiration and a lower pressure for expiration, both of which are above the ambient pressure.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Discomfort with CPAP – Patients perceive an increased work of breathing. – The straps and mask may be uncomfortable. – Airflow can dry their eyes. – The device may interfere with normal sleep. • Complications of CPAP – Skin breakdown – Gastric distension. It is typically avoided in patients with recent gastric or esophageal surgery; however, it has not been shown to increase the incidence of anastomotic leakage following gastric bypass. – May be associated with stress ulcers – May cause barotrauma if pressures are too high (pressures <25 cm H2O are typically safe). • Increases mortality in patients with postextubation hypoxemic respiratory failure following a course of prolonged mechanical ventilation, possibly due to a delay in reintubation.

PERIOPERATIVE RELEVANCE

• Laryngospasm. 100% oxygen using CPAP splints the airway and stretches laryngeal muscles, attenuating the contraction of actin and myosin fibrils. Initiate CPAP as soon as possible (<15 seconds) because the longer a muscle is in spasm, the stronger the contraction becomes and the more difficult it is to overcome. CPAP will not break complete laryngospasm because forced inflation of the pharynx distends the piriform fossa on either side of the larynx and presses the aryepiglottic folds more firmly against each other. Oxygen will fill the stomach instead of the lungs. • In postoperative patients, CPAP is as effective as incentive spirometry in reducing atelectasis and improving gas exchange. • Possibly decreases morbidity. CPAP use has been shown to reduce the incidence of reintubation, pneumonia, and sepsis, as well as decrease the duration of intensive care unit (ICU) stay. • Maintenance of upper airway patency. CPAP during induction or extubation helps maintain patency, particularly in children. • Obesity. Application of CPAP (6 cm H2O) for 5 minutes prior to induction, followed by 5

minutes of mechanical ventilation with PEEP in sedated patients has been suggested to be superior to PEEP alone (5). • Postlung resection. CPAP improves lung efficiency with gas exchange without undesired side effects; it does not increase the pleural air leak or dead space to tidal volume ratio. It has also been shown to reduce the incidence of reintubation and mortality. • One lung ventilation. May be useful for the non-dependent and non-ventilated lung. – It causes diversion of blood flow to the dependent (perfused) lung. – 5–10 cm of H2O reduces shunt to nonventilated lung ratio, allowing for increased

oxygenation. – Not useful in patients undergoing video-assisted thoracoscopy, as it can impede visualization. • Acute cardiogenic pulmonary edema. Earlier improvement and resolution of dyspnea, respiratory distress, and metabolic abnormalities when compared to treatment with standard oxygen therapy. • Bridge from invasive to spontaneous ventilation in patients who pass weaning trials, but are at risk for failing extubation in the ICU setting. – Risk factors include More than one comorbid condition COPD Congestive heart failure APACHE score >12 Age >65 years Ineffective cough Excessive secretions Previous weaning failures Upper airway obstruction – A favorable response to CPAP is typically apparent within the first hour. – Absence of improvement strongly suggests the need for tracheal intubation. • Obstructive sleep apnea (OSA). CPAP may be used at home during sleep to prevent redundant upper airway tissue from causing a “variable extrathoracic" obstruction. Soft tissue collapse obstructs the airway, leading to hypoventilation and stridor (snoring). With positive pressure inhalation, the redundant tissue is “pushed out of the way" allowing air to enter the lung. – CPAP is indicated for episodes of nocturnal hypoxemia or retention of CO2 that are

diagnosed following a sleep study. – Successful use of CPAP in an obese patient suggests that the patient can be ventilated with a mask. – CPAP may prevent postoperative atelectasis in the morbidly obese patient. – Patients on CPAP at home should be instructed to bring their CPAP machines into the hospital when they present for surgery. • Patients are weaned from CPAP by gradually reducing the CPAP pressure and/or increasing the amount of time each day without the pressure support.

REFERENCES

1. Antonelli M, Conti G. Noninvasive positive pressure ventilation as treatment for acute respiratory failure in critically ill patients. Crit Care. 2000;4(1):15–22. 2. Keenan SP, Sinuff T, Cook DJ, et al. Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation? A systematic review of the literature. Ann Intern Med. 2003;138(11):861–870. 3. Epstein SK. Weaning from mechanical ventilation. Respir Care. 2002;47(4):454–466. 4. Campbell RS, Davis BR. Pressure-controlled versus volume controlled ventilation: Does it

matter? Respir Care. 2002;47(4):416–424. 5. Brochard L, Mancebo J, Wysocki M, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995;333(13):817–822. 6. Gray A, Goodacre S, Newby DE, et al. Noninvasive ventilation in acute cardiogenic pulmonary edema. N Engl J Med. 2008;359(2):142–151.

7. Aquilό R, Togores B, Pons S, et al. Noninvasive ventilatory support after lung resectional surgery. Chest. 1997;112(1):117–121. 8. Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004;350(24):2452–2460.

ADDITIONAL READING

• Longnecker DE, Brown D, Newman M, et al. Anesthesiology. New York, NY: McGraw Hill; 2008.

See Also (Topic, Algorithm, Electronic Media Element)

• Positive-end expiratory pressure (PEEP) • Obesity hypoventilation syndrome (OHS)/ Pickwickian syndrome • Laryngospasm • Atelectasis

CLINICAL PEARLS

• CPAP is commonly used in the operative setting to maintain airway patency during mask ventilation and to terminate laryngospasm. • Frequently used at home by those with obstructive sleep apnea. • Patients who use home CPAP should be instructed to bring their machines to the hospital prior to surgery. • CPAP is effective in reducing atelectasis and improving oxygenation in postoperative patients. • NPPV and CPAP are used to manage acute and chronic respiratory failure in many patients, and some patients with heart failure. • The use of CPAP should not delay tracheal intubation in patients in acute respiratory failure. • Noninvasive ventilation can preserve normal swallowing, feeding, speech, cough, and physiologic air warming and humidification.

CONTROLLED HYPOTENSION William David Stoll, MD Catherine Dawson Tobin, MD

BASICS DESCRIPTION

• Controlled hypotension is also known as deliberate or induced hypotension. It is an anesthetic technique (first described in 1917 by Dr. Cushing) that is implemented to reduce bleeding and the need for blood transfusions, as well as provide a “bloodless” surgical field in certain scenarios. – It is specifically mentioned in the ASA’s Practice Guidelines for Perioperative Blood Transfusion and Adjuvant Therapies. • Deliberate hypotension is achieved by utilizing one (or a combination of) drugs and/or volatile agents to deliberately lower a surgical patient’s BP. Agents are titrated to achieve one of the following endpoints: – Reduction in the baseline mean arterial pressure (MAP) of 30% – Goal MAP of 50–65 mm Hg – Reduction in the systolic arterial pressure to 80–90 mm Hg (1)[A]. Physiology Principles

• Controlled hypotension is postulated to reduce blood loss by decreasing arterial and venous bleeding. It is most commonly utilized in orthopedic, neurosurgical, plastics, and vascular cases to improve surgical visualization, reduce operative time, and total blood loss. • BP can be measured by either a noninvasive BP cuff or invasive arterial catheter (allows beat-to-beat monitoring). • Reductions in BP and MAP to the above-specified range can be achieved by reducing cardiac output, preload, and/or afterload. • There are several drugs and techniques that can be utilized; they are categorized as primary, secondary, or both. – Primary methods can be used alone; they include regional anesthesia, volatile agents, sodium nitroprusside, remifentanil, nitroglycerin, trimethaphan, alprostadil, and adenosine. – Secondary methods are used adjunctively to limit the dosages needed or attenuate adverse effects of other drugs or techniques. They include ACE inhibitors (captopril), clonidine, dexmedeto- midine, opioids, and propofol (1)[A]. – “Both” describes agents that can be used alone or in combination and include betablockers (labetalol, esmolol, propranolol), calcium-channel blockers (verapamil, diltiazem, nicardipine), and fenoldopam. • Hemodynamics. Vasodilators can decrease afterload and improve left ventricular function as well as decrease cardiac work and oxygen consumption. Additionally improved LV ejection can reduce the LVEDV/LVEDP and possibly improve coronary perfusion (however, this must

be balanced against decreased diastolic blood pressure; see below).

ANATOMY

• BP measurements are typically performed in the upper extremities utilizing either a NIBP cuff or an arterial line. • The NIBP cuff can be used in the lower extremities. The arterial catheter is usually placed in a radial artery but other options exist such as ulnar, femoral, and dorsalis pedis sites. However, systolic BP readings in the leg can run 10–20% higher than the brachial artery pressures.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Although there are potential benefits, the anaesthetist needs to weigh them against the risks in each individual patient. • General risks include impaired perfusion and hypoxia of vital organs and microcirculatory dysregulation. This is often difficult to discern as adequate oxygen delivery is an evermoving target that is altered by BP, hemoglobin content, oxygen saturation, tissue extraction, and utilization. – Cerebrum. CPP = MAP − ICP; where CPP is cerebral perfusion pressure, ICP is intracranial pressure. – Myocardium. No ideal number exists in regard to optimal cardiac perfusion pressures. Coronary perfusion is equal to the diastolic blood pressure minus the left ventricular end diastolic pressure. Controlled hypotension can decrease the DBP but can also decrease afterload and myocardial oxygen consumption. As discussed above, LVEDV/LVEDP may be decreased and can offset decreases in coronary perfusion pressure as well. Additionally, because the LV is only perfused during diastole, the heart rate also becomes an important factor. – Renal concerns Studies in patients with no preexisting renal disease have demonstrated that autoregulation generally remains intact with a MAP between 80 and 180 mm Hg More recent information suggests that the kidneys do not seem to incur damage with MAPs of 50–60 mm Hg Renal compensatory mechanisms appear to be well preserved at MAPs to 60 mm Hg for >200 minutes (2)[B] One study showed that MAPs of 50 mm Hg for approximately 120 minutes resulted in decreased urine flow rate, effective renal blood flow, osmolar clearance, and endogenous creatinine clearance; however, all parameters returned to normal after cessation of anesthesia (3)[B]. – Hepatic concerns. The extent of autoregulation is unknown. Studies in patients with no preexisting hepatic disease have suggested that MAPs between 50 and 60 mm Hg did not appear to result in ischemia or affect autoregulation. Liver enzymes do not typically increase, and when they are elevated they returned to normal after 14 days (4)[B]. • Patients with end-organ disease are at increased risk for ischemia or hypoperfusion – Cerebral disease

With chronic hypertension, the cerebral autoregulation curve is shifted to the right One well-controlled study by Williams-Russo et al (5), however, demonstrated no longterm cognitive dysfunction in patients with end-organ disease (44% of 117 patients had baseline HTN) at MAPs between 45 and 55 mm Hg suggesting that at these pressures the metabolic requirements of the brain are met (4)[A] Carotid stenosis results in maximal dilation distal to the lesion; thus, drops in BP cannot be compensated by further vasodilation to maintain flow – Cardiac disease Chronic and significant hypertension alter the autoregulation range Significant stenotic valve lesions have a fixed cardiac output and drops in SVR or the reflexive tachycardia that may occur with controlled hypotension are not well tolerated Atherosclerotic vessels are perfusion-dependent; vessels are maximally vasodilated just distal to the lesion (similar to carotid stenosis) – Renal. Acute on chronic renal dysfunction can result from intraoperative hypoxia or hypotension.

PERIOPERATIVE RELEVANCE

• The major indication for imposing controlled hypotension is to reduce bleeding: – Provides a favorable and clear surgical field and may increase the quality and speed of a surgical procedure (6)[B]. – Decreases the need for blood product transfusion. This is generally welcomed secondary to the concerns of infection and adverse systemic reactions (7)[A]. • Appropriate adjuncts should be implemented to aid in monitoring end-organ perfusion and function as well as volume status. They include, but are not limited to – Hemodynamic variables such as pulse pressure waveform variation in pulse oximetry and arterial line waveforms aid with assessing volume status – EKG rhythm analysis to asses myocardial perfusion and oxygenation – ETCO2 reduces from “dead space” pathophysiology (decreases in BP reduce alveolar perfusion and exhalation of CO2)

– Urine output is an indicator of renal perfusion – BIS/EEG/SSEP/MEP monitoring to assess neural perfusion and oxygenation – Blood gas analysis (pH, CO2, HCO3, base deficit) can indicate metabolic acidosis from

anaerobic metabolism (lactate production). – CVP trends can aid with volume assessment – Mixed venous O2 aids with assessing oxygen delivery and utilization at the tissue level.

• Of note, none of these methods guarantee end-organ perfusion but are adjunctive to clinical impression. • Hemodynamics – The effect of controlled hypotension on HR, SVR, and ischemia varies based on the drug or drugs used to achieve the hypotensive state. The overriding concern is ischemia, and trying to gauge the level of hypotension that can safely be handled by patients with preexisting cardiac conditions is sometimes difficult. Patient-specific decisions are certainly warranted in this case.

EQUATIONS

• BP = CO × HR; BP is blood pressure, CO is cardiac output, and HR is heart rate – Normal = 120/80 mm Hg • MAP = [(2 × DBP) + SBP]/3; where MAP is mean arterial pressure, DBP is diastolic blood pressure, and SBP is systolic blood pressure – Normal = 70–110 mm Hg • CPP = MAP – RAP (or ICP if greater); where CPP is cerebral perfusion pressure, MAP is mean arterial pressure, RAP is right atrial pressure, and ICP is intracranial pressure – Normal = between 70–90 mm Hg

REFERENCES

1. Tobias JD. Controlled hypotension in children: A critical review of available agents. Paediatric Drugs. 2003;4(7):439–453. 2. Toivonen J, Kaukinen S, Oikkonen M, et al. Effects of deliberate hypotension induced by labetalol on renal function. Eur J Anaesthesiol. 1991;8:13–20. 3. Lessard MR, Trepanier CA. Renal function and hemodynamics during prolonged isofluraneinduced hypotension in humans. Anesthesiology. 1991;74:860–865. 4. Fukusaki M, Miyako M, Hara T, et al. Effects of controlled hypotension with sevoflurane anaesthesia on hepatic function of surgical patients. Eur Acad Anesthesiol. 1999;16:111– 116. 5. Williams-Russo P, Sharrock NE, Mattis S, et al. Randomized trial of hypotensive epidural anesthesia in older adults. Anesthesiology. 1991;91(4):926–935. 6. Enderby GEH. The advantages of controlled hypotension in surgery. Br Med Bull. 1958;14(1):49–51. 7. Choi WS, Samman N. Risks and benefits of deliberate hypotension in anaesthesia: A systematic review. Int J Oral Maxillofac Surg. 2008;37(8):687–703.

ADDITIONAL READING

• Textbook of Neuroanaesthesia and Critical Care. 1st Edition, 2000. Edited by Basil F. Matta, David K. Menon, and John M. Turner. • Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 21th Edition, 2011. Edited by Laurence Brunton, Bruce Chabner, and Bjorn Knollman.

See Also (Topic, Algorithm, Electronic Media Element) • Scoliosis • Cerebrovascular disease • Perioperative blindness • Blood transfusion infection • Mixed venous oxygen saturation

CLINICAL PEARLS

• For surgical procedures that may benefit from controlled hypotension, the risks for the individual patient should be assessed. • Patients at risk for end-organ damage should be discussed with the surgeon. • Ensure that a reliable method of determining BP is used.

COOLING OF THE HEART January Y. Tsai, MD

BASICS DESCRIPTION

• Myocardial cooling is used to limit ischemic injury during cardiac arrest or surgical procedures requiring cessation of blood flow to the myocardium. Examples include – On pump coronary artery bypass grafting (OPCABG) – Open valve repair or replacement – Cardiac aneurysm repair – Ascending aorta or aortic arch repair • The therapeutic effects stem from reducing the metabolic rate and hence optimizing the myocardial O2 supply:demand ratio. PHYSIOLOGY PRINCIPLES

• Myocardial O2 consumption results from:

– Mechanical/contractile processes (~80% of O2 consumption)

– Basal O2 consumption (~20% of O2 consumption)

– Electrical/conduction processes (~0.5% of O2 consumption) (1)

• Myocardial O2 consumption varies as a function of temperature and contractility – 37°C NSR at rest: 6–8 mLO2/100 g/min

– 37°C NSR heavy exercise: 70 mLO2/100 g/min – 37°C VF: 4 mLO2/100 g/min

– 37°C Empty beating: 3 mLO2/100 g/min – 37°C Asystole: 1–2 mLO2/100 g/min

– 15°C Empty beating: 0.4 mLO2/100 g/min

– 15°C Asystole: 0.3 mLO2/100 g/min (2)

• Cooling of the heart decreases mechanical/contractile processes as well as cell “housekeeping” activities, while maintaining cell membrane integrity (Na+–K+ ATP synthase). Additionally, – ATP consumption: Decreases – Heart rate: Decreases – Cardiac output: Decreases by 7%/1°C – Stroke volume: Unchanged – Arterial pressure: Unchanged – Enzyme Q10: Reaction rate halves for every 10°C decrease in temperature; normally ∼2 (3)

• The putative molecular basis of myocardial protection consists of – Reduced inflammation – Modified cell death signaling pathways – Preserved mitochondrial protein gene expression – Decreased EKR1/2 enzyme phosphorylation – Decreased COX-2 expression – Upregulation of Akt transcription factor in cardiomyocytes with preserved cell survival (4) • Cardioplegia solution is utilized to halt electrical activity with consequent therapeutic arrest of cardiomyocyte contractility. Cold cardioplegia (∼4°C) containing a high potassium (K+) concentration of 20–30 mmol/L is administered to prevent cellular repolarization; it is delivered via the coronary sinus (retrograde), aortic root (antegrade), and/or coronary ostia. Since the resting potential of the ventricular myocardium is about –84 mV at an extracellular K+ concentration of 5.4 mmol/L, raising the K+ concentration to 16.2 mmol/L increases the resting potential to –60 mV, a level at which muscle fibers are inexcitable to ordinary stimuli. Theoretically, cold cardioplegia solution decreases O2 consumption from 6–8 mLO2/100 g/ min to 0.3 mLO2/100 g/min.

DISEASE/PATHOPHYSIOLOGY

• Systemic physiologic effects of hypothermia include – Cold diuresis – Alkalosis – Hypokalemia – Increased infection risk – Mild coagulopathy – Hyperglycemia • Effects of inadequate cooling include – Myocardial ischemia – Arrhythmia – Cardiac stunning – Difficulty weaning from CPB • Causes of inadequate cardioplegia administration include – Improper cannula placement (right atrium instead of CS) – Significant aortic insufficiency – Severe occlusive coronary disease physically hindering distribution of cardioplegia solution – Infrequent cardioplegia administration – Inadequate volume of solution – Incorrect potassium concentration • Significant aortic insufficiency – Retrograde flow through the aortic valve prevents adequate antegrade cardioplegia delivery to the coronary arteries. – May require retrograde cardioplegia via the CS. – In a study of 84 consecutive patients undergoing CABG, TEE allowed accurate calculation of the severity of aortic regurgitation, which was significantly associated with the need for

retrograde cardioplegia administration (5). • Ventricular fibrillation – Likely with profound hypothermia (<25°C) – Abnormal conduction may require pacing.

PERIOPERATIVE RELEVANCE

• Myocardial protection through decreasing the metabolic rate is crucial with preexisting coronary disease. • Cooling of the heart can occur concurrent with systemic cooling: – External cooling with ice pack or a heat exchange device – Endovascular cooling – Infusion of cold intravenous fluids – Gastric lavage – Urinary bladder lavage • Temperature measurement – Locations include nasopharynx, esophagus, bladder, and rectum. • Body size – May affect duration of cooling and rewarming times • TEE – Bicaval and midesophageal four-chamber views are useful for evaluating cardiac contractility, segmental wall motion, and to assist retrograde cannula placement. • Coronary artery disease – Inadequate delivery of cold cardioplegia solution may occur due to physical occlusion of the coronary arteries may require retrograde administration.

REFERENCES

1. raunwald E. The determinants of myocardial oxygen consumption. Thirteenth Bowditch Lecture, XXIV International Congress of Physiological Sciences, Washington, D.C., August 30, 1968. 2. essen M, Abd-Elfattah AS, Wechsler AS. Neonatal myocardial oxygen consumption during ventricular fibrillation, hypothermia, and potassium arrest. Ann Thorac Surg. 1996;61:82– 87. 3. Hamamoto H, Sakamoto H, Leshnower BG, et al. Very mild hypothermia during ischemia and reperfusion improves postinfarction ventricular remodeling. Ann Thorac Surg. 2009;87:172–177. 4. Drescher C, Diestel A, Wollersheim S, et al. How does hypothermia protect cardiomyocytes during cardioplegic ischemia? Eur J Cardiothoracic Surg. 2011;doi:10.1016/j.ejcts.2010.12.006. 5. Moisa RB, Zeldis SM, Alper SA, et al. Aortic regurgitation in coronary artery bypass grafting: Implications for cardioplegia administration. Ann Thorac Surg. 1995;60(3):665– 668. 6. Tissier R, Chenoune M, Ghaleh B, et al. The small chill: Mild hypothermia for cardioprotection? Cardiovasc Res. 2010;88:406–414.

See Also (Topic, Algorithm, Electronic Media Element) • Cardiopulmonary bypass (CPB) • Cardioplegia • Hypothermia • Circulatory arrest

CLINICAL PEARLS

• Hypothermia combined with cardioplegia is commonly used for cardioprotection. • Optimal temperature remains unknown. • Systemic hypothermia can have neuroprotective effects. • TEE assists retrograde CS cannula placement. • Mild hypothermia (32–35°C) is beneficial for cardioprotection with STEMI or resuscitation after cardiac arrest when instituted expeditiously (6). – The cardioprotective effects of hypothermia are greatest when cooling is initiated within 20 minutes after the onset of ischemia. – Following coronary artery occlusion, infarct size was progressively reduced with decreasing temperature from 39.5 to 35.4°C (3). Overall, hypothermic myocardial protection decreased metabolic requirements and minimized ischemic insult.

COR PULMONALE Erik E. Abel, PharmD, BCPS Ravi S. Tripathi, MD

BASICS DESCRIPTION

• Cor pulmonale consists of right ventricular (RV) impairment or failure in the absence of left ventricular (LV) disease. It is secondary to acute or chronic abnormalities of the pulmonary circulation, lungs, or thorax and is sometimes referred to as “pulmonary” heart failure. • It can be diagnosed by noninvasive assessment of RV function using EKG and invasively via pulmonary artery catheterization; however, for both of these modalities, diagnostic criteria are not standardized. EPIDEMIOLOGY Incidence

• Unknown; poorly studied in the population of patients undergoing general anesthesia. • RV failure occurs in ~30% of patients after left ventricular assist device placement (LVAD).

Prevalence

Greater in patients with underlying pulmonary disease that contributes to chronic hypoxic states Morbidity

• Cor pulmonale and pulmonary hypertension (PH) are associated with a 13.1-fold increase in perioperative morbidity and mortality when undergoing noncardiac surgery compared to cross-matched patients without PH (1). – More likely to develop congestive heart failure (OR = 11.9) – Susceptible to more hemodynamic instability and respiratory failure – Patients were shown to need longer ventilator support, stay longer in the intensive care unit (ICU), and have higher readmission to the hospital within 30 days of surgery. Mortality

• Despite equivalently smooth operative courses, PH patients had increased in-hospital deaths compared to matched controls (9.7% vs 0%); systolic pulmonary artery pressure (PAP) served as an independent predictor of mortality (2). • These patients also had significantly more frequent postoperative heart failure and delayed extubation. ETIOLOGY/RISK FACTORS

• Cor pulmonale and RV failure can be either acute or chronic. • Acute etiologies include thromboembolic disease, cardiac tamponade, RV ischemia, and

acute chest syndrome with sickle cell disease • Chronic etiologies include chronic obstructive pulmonary disease, obstructive sleep apnea, valvular disease, congenital heart disease, PH, and collagen-vascular disease

PATHOPHYSIOLOGY

• Similar to the LV, the RV stroke volume is affected by preload (central venous pressures), afterload (pulmonary artery pressures and pulmonary vascular resistance), and contractility. • In contrast to the LV, the RV has ~1/6th the muscle mass, decreasing its ability to pump effectively against an increased afterload. It functions more as a volume pump than a pressure pump. • Elevations in RV afterload can result in • Acute: Dilation of the RV • Chronic: Hypertrophic response to improve contractile forces against the increased tension; recall LaPlace’s law. This results in decreased compliance and impaired diastolic filling. • In low cardiac states, compensation is primarily with a tachycardic response due the the RV’s limited ability to respond with greater contractile force. The RV is more prone to overt failure when faced with decreased preload (vasodilatory states), increased afterload (hypoxia, hypercarbia, coughing, bucking), or decreased contractility (ischemia, anesthetics). • Hypoxemia. The degree of hypoxemia and inability to maintain arterial oxygenation is directly associated with the development of PH and RV failure. Hypoxia induces pulmonary vasoconstriction (increased PVR), which in turn increases the risk of RV strain and failure. • Arrhythmias • Atrial (more common) or ventricular arrhythmias can develop. • Inhaled beta-agonists may induce tachycardias. • Systemic beta antagonists may worsen bronchospastic status, thus creating further complications. • Hepatic congestion secondary to venous congestion is common, usually evident by elevations in transaminases and INR. This may partially subside with optimization of cor pulmonale.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients should be optimized prior to elective surgery. Control infections and bronchospastic diseases prior to administering anesthesia. • Pulmonary hygiene should be focused on the clearance of secretions and recruiting poorly ventilated units of lung in order to optimize oxygenation and ventilation. • Avoid acute increases in the PAP (hypoxia, hypercarbia, acidosis, increased sympathetic states), or decreases in contractility. • Volume optimization must be carefully assessed and addressed. Hypovolemia will decrease preload and RV output; whereas fluid overload may exacerbate arrhythmias and RV strain.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Peripheral edema and ascites, often presenting as ankle edema and congestive hepatomegaly • Distress during mild exertion or rest, not relieved by sitting upright (in contrast to orthopnea present in patients with LV failure) • Nonproductive cough • Other classically associated symptoms of heart failure

History

• Dyspnea and tachypnea often overlap with underlying pulmonary disease. • Severity of underlying disease: Exercise tolerance, need for bronchodilators, or supplemental oxygen • Exacerbations: Fatigue, worsening dyspnea, and increased oxygen requirements

Signs/Physical Exam

• Cardiac examination: A right-heave may be palpated along the left sternal border or in the epigastrium; an augmented pulmonic component of the second heart sound; and associated murmurs due to incompetence of the tricuspid valve (during systole) and/or pulmonic valve exist (during diastole). Both murmurs are augmented by inspiration. • Peripheral edema, jugular venous engorgement, and positive hepatojugular reflex

TREATMENT HISTORY

• Options are focused primarily on maintaining and restoring oxygenation and ventilation to decrease PVR, volume status, and RV workload. • Supportive therapy of oxygen is important to maintain a PaO2 >60 mm Hg or SpO2 >90%. • Lung transplantation in severe disease

MEDICATIONS

• Anticoagulation for thromboembolic disease • Heart failure regimens (diuretic therapy) may be needed to manage peripheral edema but can also impair RV function (decreased preload and metabolic alkalosis). • Calcium channel blockers (CCBs) are a first-line outpatient treatment, although many are not candidates or responders to these. These agents can exacerbate perioperative hypotension and can increase mortality risk in patients with systolic dysfunction. • Phosphodiesterase inhibitors and endothelin antagonists • While not FDA approved for this use, inhaled nitric oxide (iNO) and inhaled epoprostenol have been used to treat acute crises (RV failure, hypoxemia, and PH). DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Arterial blood gas: Objectively assess the degree of respiratory insufficiency. • Liver function tests: Dysfunction and coexisting coagulopathy • EKG: Findings include RV enlargement, ventricular septal flattening “D-sign,” ventricular dysmotility, and evidence of elevated estimated RV systolic pressure. • Chest x-ray: A decrease in the retrosternal space on lateral films indicates RV hypertrophy. A prominent main pulmonary artery and decreased vascular markings may be consistent with PH.

• Echocardiogram: Right atrial and RV hypertrophy (peaked P waves in leads II, III, and aVF). Right axis deviation and right bundle branch blocks can also be seen. • Pulmonary function tests: Assess the response to bronchodilator therapy. • Right atrial pressure tracing: Predominant A wave due to enhanced right atrial contraction with decreased ventricular compliance. • Right heart catheterization: Elevated PAP with normal pulmonary artery occlusion pressures (representing normal left ventricular end-diastolic pressure, LVEDP). • Cardiac MRI: While not widely available, can provide accurate information on RV function.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Maintaining oxygenation and ventilation is imperative; thus, medications that may depress ventilation (i.e., opioids) should be used judiciously. • Inhaled beta-agonists may be needed to optimize pulmonary disease.

Special Concerns for Informed Consent

Increased risk of perioperative complications, morbidity, and mortality INTRAOPERATIVE CARE Choice of Anesthesia

• Dependent on the procedure. As a sole technique, regional anesthesia has the benefit of avoiding anesthetic induction, airway instrumentation, mechanical ventilation, and extubation, as well as minimizing systemic opioids. However, supplemental sedation, failed blocks, or complications of the block (e.g., high spinal and local anesthetic toxicity) need to also be considered. Additionally, patients may not be able to lie flat during a procedure. • Supplementing the general anesthetic with a regional technique has the benefit of decreasing the need for systemic opioids. • Caution should be exercised when performing regional techniques that can affect respiratory parameters. Interscalene blocks can cause phrenic nerve palsies (C3, C4, C5); neuraxial techniques to the T6 level can affect accessory muscles of respiration. Monitors

• Standard ASA monitors • Invasive monitoring is dependent on the degree of patient dysfunction and the operative procedure. • Arterial line. Monitoring arterial line BP helps identify rapid changes in hemodynamics and allows frequent blood gas measurements of PaO2 and PaCO2 (can aid with decision to

extubate). • Central lines can assess RV pressures. • Pulmonary artery catheters. May be used to assess the degree of patient illness, effect of fluid shifts and changes in acid/base status from hypercarbia, laparoscopy, etc. by

monitoring the PAPs. • An alternative to invasive monitoring includes transesophageal echocardiogram; however, this monitor requires expertise and is usually employed only while the patient is intubated

Induction/Airway Management

• To minimize increases in PVR, patients should have an adequate depth of anesthesia prior to instrumenting the airway. • Supraglottic devices (i.e., LMA) may decrease airway stimulation; however, adequate ventilation must be ensured to prevent respiratory acidosis. • The RV can also be preload dependent against the fixed afterload of PH. Anesthetic selection must avoid sympathetic spikes without dropping systemic vascular resistance.

Maintenance

• N2O is controversial with conflicting evidence on its effects on PVR. Monitoring the right atrial or PAP can allow early identification of intolerance and allow discontinuation. • Neuromuscular blockade (and other anesthetic drugs) should avoid histamine release. • Fluids should be titrated judiciously; patients can be sensitive to hypovolemia and require a sufficient preload to maintain the RV output. However, hypervolemia can overload the Frank–Starling curve of the RV and lead to strain or failure and worsening venous congestion.

Extubation/Emergence

• Extubation. Standard criteria apply; however, patients may be less capable of meeting them. If adequate ventilation and oxygenation cannot be ensured, consider delaying extubation. Deep extubation can result in inadequate ventilation and hypercarbia. • A smooth emergence with minimal coughing is desired to prevent increased intrathoracic pressure, RV afterload, and sympathetic input. • Tracheal application of lidocaine may be helpful to minimize the response to airway instrumentation.

REFERENCES

1. Kaw R, Pasupuleti V, Deshpande A, et al. Pulmonary hypertension: An important predictor of outcomes in patients undergoing non-cardiac surgery. Respir Med. 2001;105:619–624. 2. Lai HC, Lai HC, Wang KY, et al. Severe pulmonary hypertension complicates postoperative outcome of non-cardiac surgery. Br J Anaesth. 2007;99(2):184–190. 3. Lahm T, McCaslin CA, Wozniak TC, et al. Medical and surgical treatment of acute right ventricular failure. J Am Coll Cardiol. 2010;56(18):1435–1446. 4. Jardin F, Viellard-Baron A. Acute cor pulmonale. Curr Opin Crit Care. 2009;15(1):67–70. 5. Veillard-Baron A, Jardin F. Why protect the right ventricle in patients with acute respiratory distress syndrome? Curr Opin Crit Care. 2003;9(1):15–21.

ADDITIONAL READING

• Haddad F, Couture P, Tousignant C, et al. The right ventricle in cardiac surgery, a

perioperative perspective: I. Anatomy, physiology, and assessment. Anesth Analg. 2009;108(2):407–421. • Haddad F, Couture P, Tousignant C, et al. The right ventricle in cardiac surgery, a perioperative perspective: II. Pathophysiology, clinical importance, and management. Anesth Analg. 2009;108(2):422–433. See Also (Topic, Algorithm, Electronic Media Element)

• Obstructive sleep apnea • Epidural • Deep extubation

CODES ICD9 • 415.0 Acute cor pulmonale • 416.9 Chronic pulmonary heart disease, unspecified ICD10 • I26.09 Other pulmonary embolism with acute cor pulmonale • I27.81 Cor pulmonale (chronic)

CLINICAL PEARLS

• Management and support of cor pulmonale include the avoidance of hypercarbia, hypoxia, and heightened sympathetic states. • Further treatment requires application of physiologic principles through decreasing RV afterload, while maintaining preload and contractility. • Tachycardia is an appropriate compensatory response to RV dysfunction and should be treated cautiously. • Laparoscopy may be poorly tolerated; it is associated with hypercarbia and decreased venous return due caval compression.

CORNEAL ABRASIONS John L. Ard Jr., MD T. Kate Huncke, MD

BASICS DESCRIPTION

• Corneal abrasion is the most common ocular injury during nonocular surgery. • It usually does not lead to permanent injury, but can be the cause of great pain and discomfort in the postoperative period. EPIDEMIOLOGY Incidence

1.51 cases per 1,000 nonocular surgeries Morbidity

• Usually resolves within 24–72 hours with proper treatment. • In one study, 16% of corneal abrasions resulted in permanent injury.

ETIOLOGY/RISK FACTORS

• Direct trauma and chemical irritation (responsible for 20% of injuries): – Face mask – Anesthesia provider’s stethoscope, wrist watch, protective face shields, or badge – Laryngoscope blade – Airway placement – Suction – Central venous line insertions – Laryngeal mask airway placement – Drapes – Patients hands or fingers as they rub their eyes after emergence with the index finger and the pulse oximeter attached – Patients lying laterally after emergence while still slightly sedated • Lagophthalmos is the term to describe the inability to close the eyelids completely. Under general anesthesia, incomplete closure (and taping) can result in dry eye; accounts for 80% of injuries. • Lateral or prone position • Head and neck surgery. The surgical field is located near the eyes and increases the possibility of trauma by the surgical team and inadvertent instillation of antimicrobial preparation solutions (1)[A]. • Longer surgical duration; less common in pro- cedures <1 hour (2)[A]. • Zygomaticomaxillary complex fractures are associated with minor (55%) and major (10%) ocular injuries (3)[B]. Consider preoperative evaluation to ascertain baseline.

• Tear production. Decreases can result in drying of the corneal epithelium. It is affected in certain populations: – Diabetics have decreased tear production and increased corneal sensitivity (4)[B]. – Menopausal and postmenopausal women have decreased production due to serum prolactin and sex hormone levels. – Premature infants have decreased production until a mean postconceptual age of 8.5 months (5)[B]. – Women under the age of 41 have an increase in tear flow and lower tear osmolality; no difference in corneal abrasions has been noticed, however (6)[C]. – Rheumatoid arthritis with Sjögren’s syndrome has decreased tear production.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The cornea is the outer most layer of the eyeball. The external surface of the cornea is a layer of delicate epithelium that is continuous with the conjunctiva. • Dry eye. An inadequate supply of oxygen to the cornea produces edema and in the presence of a dry environment, desquamation of the epithelial layer readily occurs, producing an abrasion. • General anesthesia: – Reduces basal tear production – Abolishes the blink reflex – Decreases the tone of the orbicularis oculi that normally keeps the eyelid closed – Abolishes Bell’s phenomenon (the eyeball turns upward during normal sleep)

PREVENTATIVE MEASURES

• Manually close eyes and tape them shut as soon as the patient loses consciousness after the induction of general anesthesia (7)[C]. Check to make sure the eye is completely closed. Eye injury may occur if the patient opens their eyes prematurely beneath the tape or with removal of the tape (8)[A]. • Intermittent checks to ensure that there is no inadvertent eyeball compression, particularly in the lateral or prone position or head and neck surgeries. • Op-sites or bio-occlusive dressings may be considered in prone, lateral, prolonged procedures, or head and neck surgery. They offer protection as well as prevent drying and exposure to contaminants (cleaning solutions). • Water-based eye ointment. Studies have not shown that this significantly reduces the incidence of injury. Additionally, patients may be more likely to rub their eyes to improve visualization. • Corneal protectors or shells may be considered when facial injuries or burns or the procedure prevent taping or op-site. • Soft contact lenses • Protective goggles are rigid and prevent inadvertent compression of the cornea. • Tarsorrhaphy sutures (suture the eyelids closed). • Geliperm is a sterile, transparent, pliant hydrogel dressing that allows for continuous observation of the eye (9)[C]. • Laser eye protection for the patient includes taping closed and placing wet sponges over the eye, taping the sponges on the face, and placing a metal shield over it. Alternatively, laser

goggles can be placed.

DIAGNOSIS • An urgent ophthalmology consultation for any patient who wakes up complaining of painful eye or decreased vision. • The ophthalmologist will examine the eye with fluorescein stain and a blue light.

DIFFERENTIAL DIAGNOSIS

• Conjunctivitis • Red eye • Acute angle-closure glaucoma • Corneal ulcer • Episcleritis • Keratitis • Scleritis

TREATMENT • Small abrasions with moderate pain – Topical antimicrobials like chloramphenicol 1% ointment: Two drops every 3 hours (10) [C]. • Larger abrasions. In addition to chloramphenicol 1% ointment (10)[C]: – Topical analgesics (NSAIDS) like diclofenac drops 0.1% solution: One drop four times daily (10)[A] – Oral analgesics (10)[A]

FOLLOW-UP Re-evaluate in 24 hours; if there is improvement, there is no need to follow up unless symptoms worsen again. CLOSED CLAIMS DATA

• Eye injuries are 3% of total claims (11)[C]. – Corneal abrasions comprised the largest single group of eye injuries (25 of 71 eye injuries) (11)[C]. – Sixteen percent of corneal abrasions resulted in permanent injury (11)[C].

REFERENCES

1. Siffring PA, Poulton TJ. Prevention of ophthalmic complications during general anesthesia. Anesthesiology. 1987;66:569–570. [A] 2. atra YK, Bali IM. Corneal abrasions during general anesthesia. Anesth Analg. 1977;56:363– 365. [A]

3. amal BT, Pfahler SM, Lane KA, et al. Opthalmic injuries in patients with zygomaticomaxillary complex fractures requiring surgical repair. J Oral Maxillofac Surg. 2009;67:986–989. [B] 4. ousen P, Cackett P, Bennett H, et al. Tear production and corneal sensitivity in diabetes. J Diabetes Complications. 2007;21:371–373. [B] 5. kar Y, Cira A, Apaydin C, et al. The effect of prematurity on tear production. Curr Eye Res. 2004;28:145–151. [B] 6. raig JP, Tomlinson A. Effect of age on tear osmolality. Optom Vis Sci. 1995;72:713–717. [C] 7. hite E, Crosse MM. The aetiology and prevention of peri-operative corneal abrasions. Anesthaesia. 1998;53:157–161. [C]

8. now JC, Kripke BJ, Norton ML, et al. Corneal injuries during general anesthesia. Anesth Analg. 1975;54:465–467. [A] 9. uddihy PJ, Whittet H. Eye observation and corneal protection during endonasal surgery. J Laryngol Otol. 2005;119:556–557. [A] 10. ilson S, Last A. Management of corneal abrasions. Am Fam Physician. 2004;70:123–128. [A] 11. ild WM, Posner KL, Caplan RA, et al. Eye injuries associated with anesthesia. A closed claims analysis. Anesthesiology. 1992;76:204–208. [C] 12. artin D, Weingarten T, et al. Performance improvement system and postoperative corneal injuries. Anesthesiology. 2009;111:320–326. [B]

ADDITIONAL READING

• Batra YK, Bali IM. Corneal abrasions during general anesthesia. Anesth Analg. 1977;56:363– 365. • Cucchiara RF, Black S. Corneal abrasion during anesthesia and surgery. Anesthesiology. 1988;69:978–979.

See Also (Topic, Algorithm, Electronic Media Element) • Perioperative blindness

CODES ICD9 918.1 Corneal abrasion ICD10 • S05.00XA Inj conjunctiva and corneal abrasion w/o fb, unsp eye, init • S05.01XA Inj conjunctiva and corneal abrasion w/o fb, right eye, init • S05.02XA Inj conjunctiva and corneal abrasion w/o fb, left eye, init

CLINICAL PEARLS

• Patching the eye is no longer thought to be helpful (9)[A]. • Topical mydriatics are not effective for treatment of corneal abrasions and are not recommended (9)[B]. • Increasing awareness of corneal abrasions helps prevent the injury (12)[B]. • The injury may occur in the immediate postoperative period as well as the operating room.

CORONARY ARTERIES Sascha Beutler, MD, PhD Daniel Castillo, MD

BASICS DESCRIPTION

• The coronary arteries deliver oxygen-rich blood to the myocardium. • Epicardial coronary arteries run on the outer surface of the heart. When healthy, they are capable of autoregulation to maintain an adequate coronary blood flow (CBF) that meets oxygen demand. • Subendocardial coronary arteries run deep within the myocardium.

PHYSIOLOGY PRINCIPLES

• The coronary arteries are classified as “end-circulation,” since they represent the only source of blood supply to the myocardium. Thus, blockage of these vessels can be critical since there is typically very little redundant blood supply (unless collateral blood flow has developed). • Coronary blood flow (CBF) varies directly with the pressure difference across the coronary bed (coronary perfusion pressure; CPP) and inversely with the resistance of the coronary vasculature (CVR): CBF = CPP/CVR. – The CPP equals the arterial driving pressure minus the back-pressure to flow across the coronary bed. For the left ventricle (LV), the driving pressure is the aortic pressure during diastole (DBP). Left ventricular end diastolic pressure (LVEDP) is utilized to measure the back pressure. As its name implies, it is the pressure within the left ventricle at the end of diastole; it is dependent on preload volume, ventricular compliance, and systolic function. Thus, CPP of left ventricle = DBP − LVEDP – Resting CBF is 225–250 mL/min or 4–5% of the cardiac output. – There are pronounced systolic and diastolic coronary flow variations throughout the cardiac cycle. • Diastole. Arterial inflow primarily occurs during diastole; at least 75% of total CBF to the LV occurs during diastole. • Systole. Arterial inflow declines as venous outflow peaks, reflecting the compression of the microcirculatory vessels. During systole, the strength of compression decreases blood flow through subendocardial arteries of the LV to almost zero. Thus, the subendocardial system of the LV is the most vulnerable site for myocardial ischemia. • Myocardial oxygen consumption – Myocardial oxygen extraction is near-maximal at rest (about 75% of arterial oxygen content); by far the greatest oxygen extraction of all organs. – The major determinants of oxygen demand are heart rate, contractility, and wall stress

(preload, afterload, wall thickness); heart rate is the most important among them. – Since cardiac oxygen extraction is near-maximal under resting conditions, the primary mechanism to meet increased oxygen demand is through enhanced delivery. – The factors responsible for regulation of CBF are not well understood; various local metabolic factors are implicated. Activation of beta-adrenoreceptors (sympathetic nervous system) also leads to coronary vasodilatation.

ANATOMY

• The blood supply to the myocardium arises from the aorta behind the left and right aortic valve leaflets through two main coronary arteries: The left main and the right coronary artery (RCA). • The left main coronary artery (LMCA) extends for a short distance before dividing into the left anterior descending artery (LAD) and the circumflex coronary artery (LCX) (see Figure 1).

FIGURE 1. Coronary artery anatomy

• LAD – Courses down the interventricular groove and gives rise to the septal and diagonal branches. – The septal branches vary in number, size, and course into the interventricular septum and usually supply the anterior two thirds of the septum. – One to three diagonal branches exist and distribute blood to the anterolateral aspect of the heart. – The LAD continues down the interventricular groove and usually passes all the way around the apex of the LV. • LCX – Passes along the base of the LV within the coronary sulcus and terminates in the left posterior descending branch.

– Its main vessels are the obtuse marginal branches (one to three in number) and supply the lateral-free wall of the LV. • RCA – Arises from the anterior wall of the aortic root (also makes it prone to air entry on termination of cardiopulmonary bypass). – Passes down the right atrioventricular (AV) groove. – Usually supplies the anterior and posterior walls of the right ventricle except for the apex (supplied by LAD). – Gives rise to the acute marginal branches that supply the anterior wall of the right ventricle. – Also supplies the right atrium including the sinoatrial (SA) node in about 55% (in 45% SA node supplied by LCX), the AV node in about 90% (10% supplied by LCX), the posterior third of the septum, the inferior wall, and the base of the LV. • Coronary artery dominance – In about 80–85% of individuals, the RCA gives rise to the posterior descending artery (PDA) to supply the posterior inferior aspect of the LV; this pattern of blood supply is called a right dominant system. – In a left dominant system the LCX supplies the posterior–inferior aspect of the LV (about 10–15%). – In a codominant system, both the RCA and the LCX supply the posterior–inferior aspect of the LV (about 5–10%). • Myocardial segments – Consensus recommendations were published by the American Heart Association (AHA) on how to define 17 myocardial segments (see Figure 2) (1). The standardization of the 17 segments facilitates communication about results from the wide variety of cardiac imaging modalities currently in use for research and clinical applications. – Despite tremendous variability in the coronary artery blood supply to myocardial segments, the 17 segments were assigned to the 3 major coronary arteries.

FIGURE 2. American Heart Association consensus definitions of left ventricular segmentation. (Reused with permission from ACC/AHA 2007 Guidelines on perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary. Circulation. 2007;116:1971–1996.)

• Coronary collaterals – An extensive network of coronary capillaries are normally present from the time of birth. In normal hearts, the collaterals are not demonstrable by angiography due to their small diameter. Only enlarged collaterals (due to myocardial oxygen deprivation) are visible on angiography. – These collaterals are not visualized on angiography in normal hearts due to their small diameter. Only enlarged collaterals (due to chronic myocardial oxygen deprivation) are visible on angiography. • Blood supply of the papillary muscles – Two papillary muscles tether the mitral valve to the wall of the heart. If the papillary muscles are not functioning properly, mitral regurgitation may develop. – The anterolateral papillary muscle usually receives blood supplies from two arteries (LAD and LCX) and thus is more resistant to coronary ischemia. – The posteromedial papillary muscle is usually only supplied by one coronary artery (PDA) and thus more susceptible to ischemia.

DISEASE/PATHOPHYSIOLOGY

• Coronary artery disease (CAD) is a condition in which a plaque builds up inside the coronary arteries. It is the leading cause of death worldwide. – Cardiac catheterization (angiography) is the gold standard to determine the anatomy of the coronary blood supply in the individual patient. It can show whether CAD is present,

but it does not necessarily assess the functional significance of a lesion and comes with its own morbidity/mortality risk (see chapter on cardiac catheterization). – Alternatively, less-invasive imaging methods are on the rise to diagnose CAD: Computed tomography angiography, cardiac magnetic resonance imaging, and positron emission computed tomography (PET). – Echocardiography and nuclear tests do not provide direct information about coronary arteries. Wall motion abnormalities are correlated and extrapolated to likely artery distribution.

PERIOPERATIVE RELEVANCE

• Patients with CAD are at increased risk for an adverse perioperative event. • All patients should be evaluated preoperatively for the presence of cardiovascular risk factors; the decision should be made whether further diagnostic studies and/or interventions are warranted prior to surgery in accordance with the AHA/ACA guidelines (2,3)[B]. • 12-Lead EKG – Inferior leads (II, III, and aVF): Electrical function of the inferior heart muscle. The inferior wall is usually supplied by the RCA. – Lateral leads (aVL, I, V5, and V6): Electrical function of the lateral wall of the LV. Ischemia or infarction is typically present here, as this represents the area of greatest oxygen consumption (thick muscle, strong contractility/tension) and most tenuous supply (hypertrophy, not perfused during systole). Typically supplied by branches of the LCX. – Anterior leads (V3 and V4): Electrical function of the anterior wall of the heart. Usually supplied by the LAD. – Septal leads (V1 and V2): Electrical function of the intraventricular septum. Branches of the LAD usually supply the anterior two third of the septum.

EQUATIONS

• CBF = CPP/CVR, where: – CBF = coronary blood flow – CPP = coronary perfusion pressure – CVR = coronary vascular resistance • CPP = (diastolic systemic blood pressure – LVEDP), where LVEDP = left ventricular end diastolic pressure.

REFERENCES

1. AHA Scientific Statement. Standardized myocardial segmentation and nomenclature for tomography imaging of the heart. Circulation. 2002;105:539–542. 2. ACC/AHA 2007 Guidelines on perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary. Circulation. 2007;116:1971–1996. 3. 2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated into the ACC/AHA 2007 Guidelines on perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery. Circulation. 2009;120:e169–e276.

ADDITIONAL READING

• Ahmadi N, Nabavi V, Hajsadeghi F, et al. Mortality incidence of patients with nonobstructive coronary artery disease diagnosed by computed tomography angiography. Am J Cardiol. 2011;107(1):10–16. • Hombach V, Merkle N, Bernhard P, et al. Prognostic significance of cardiac magnetic resonance imaging: Update 2010. Cardiol J. 2010;17(6):549–557.

See Also (Topic, Algorithm, Electronic Media Element) • Coronary artery disease • Cardiac catheterization • Coronary artery bypass grafting

CLINICAL PEARLS

• Coronary arteries are the only source of blood supply to the myocardium. • There are significant blood supply variations between individuals. • Blood flow to the subendocardium of the LV nearly ceases during diastole; the subendocardium of the LV is most at risk for ischemia. • Myocardial oxygen extraction is near-maximal at rest; an increase in oxygen demand must be met primarily by an increase in blood flow at constant hemoglobin levels.

CORONARY ARTERY BYPASS GRAFTING (CABG), ON PUMP Ali Salehi, MD

BASICS DESCRIPTION General

• Coronary artery bypass grafting (CABG) was first introduced by Dr. D.W. Gordon Murray in 1953. It has since evolved with advancements in cardiopulmonary bypass (CPB), cardioplegia, and harvesting techniques. • The procedure entails an incision, followed by a sternotomy with a standard saw, exposure of the heart, and harvesting of graft conduits. • Grafts. Generally, a left internal mammary artery (LIMA) and segments of the reversed saphenous vein graft (SVG) are harvested. The LIMA is a preferred conduit because its patency rate exceeds 90% at 10 years. Advantages of a SVG include easy accessibility, availability, ease of harvest, and resistance to spasm (1). However, they have a higher incidence of atherosclerosis and deficiency of nitric oxide production compared to arterial grafts. The right internal mammary artery or radial artery can also be used depending on the patient’s history and concerns for preventing lower extremity wound infections. In the case of radial artery harvest, an “Allen test” should be performed preoperatively to confirm collateral flow. • The ascending aortic site is assessed by the surgeon prior to cannulation and clamping. Epiaortic echocardiography is indicated when plaque is noted in the aortic arch or descending aorta on transesophageal echocardiography. • Anticoagulation with heparin (300–400 units/kg) is administered to achieve an activated clotting time >400 seconds. • Cannulation. Subsequently an arterial cannula is placed in the ascending aorta proximal to the take-off of the innominate artery and a venous cannula is placed in the right atrium through the right atrial appendage. Antegrade and retrograde cardioplegia catheters are placed based upon the surgeon’s preference and clinical indication. • CPB is initiated. The body is cooled to about 30–32°C. After adequate pump flow is achieved (2–2.5 L/min/m2) and hemodynamics are optimized, cold cardioplegia is given and the aorta is cross-clamped. Warm cardioplegia can be used in the setting of severe myocardial dysfunction and low ejection fraction (EF). • Bypass targets are then determined; an appropriate target is free of disease and easily accessible. Distal anastomoses are done first and then proximal (aortic) anastomoses are performed (before or after the removal of the aortic cross-clamp). When proximal anastomoses are done after cross-clamp removal, a side clamp is placed on the ascending aorta to allow perfusion of the heart while the surgeon completes the procedure. • Rewarming. Gradual rewarming to 36°C begins after the last distal anastomosis. • The patient will be separated from CPB by gradually turning down the pump flows to zero

and supporting myocardial contractility and BP by the use of inotropes and vasopressors, as needed. Excess pump blood is retransfused to the patient and the BP controlled by administration of vasodilators like nitroglycerin, if needed. • Heparin reversal. Protamine (1 mg for every 100 units of heparin) is administered, followed by venous and arterial cannulae removal. Pleural and mediastinal chest tubes and atrial and ventricular pacing wires are placed. After adequate hemostasis is achieved, the chest is closed.

Position

• Supine, frog legged, and arms tucked to the side • Prep from chin to toes • Patient’s ankles, knees, and elbows need to be padded carefully to avoid nerve injury.

Incision

Median sternotomy Approximate Time 6–8 hours

EBL Expected 400–800 cc

Hospital Stay

5–7 days; varies based on comorbidities and complications Special Equipment for Surgery • Sternotomy saw • CPB machine • Cardioplegia

EPIDEMIOLOGY Prevalence

In the US: 228,000 annually with an annual cost of 10 billion dollars (2).

Prevalence

Increases with age, male gender, diabetes, severity, and number of vessels involved. Morbidity

Increased in patients with diabetes (blood glucose >150 mg/dL), renal disease (Cr >1.5 mg/dL), female gender, obesity, previous CVA, reoperation, and emergent surgery. Mortality

1–3%; can reach 5% in certain patient populations (3). ANESTHETIC GOALS/GUIDING PRINCIPLES • Patients often have several comorbidities.

• Understanding the stages of going “on” and “off pump,” potential complications, and close communication with the surgical team are key.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Can be asymptomatic and diagnosed during a routine check-up • Angina or angina equivalent; dyspnea, palpitation, fatigue, chest tightness, sweating, and epigastric discomfort

History

Detailed cardiac history and documentation of any recent changes Signs/Physical Exam

• Tachycardia, hypotension, and hypertension • Congestive heart failure: Leg swelling, jugular venous distention, and crackles • Arrhythmias • Pericardial friction rub • Systolic ejection murmur due to ischemic Mitral Regurgitation (MR) or rupture papillary muscle • Holosystolic murmur due to ischemic Ventricular septal defect (VSD)

MEDICATIONS

• Beta-blockers and statins should be continued perioperatively. • Aspirin should be stopped 3–5 days prior to surgery except in high-risk patients (unstable angina, recent myocardial infarction, MI). • Clopidogrel should be stopped 7–10 days prior to surgery, if possible. • ACE inhibitors, on the day of surgery, increase the incidence of hypotension on induction.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hgb/Hct and PT/INR/PTT • Electrolytes, BUN/Cr and blood urea nitrogen, BUN/creatinine • EKG (rhythm, heart block, bundle branch block, Q wave, ST-T changes, LVH) • Echocardiogram (LV and RV function, wall motion abnormalities, valvular abnormalities, patent foramen ovale) • Coronary angiogram (extent of coronary involvement, other abnormalities, pulmonary artery (PA) pressure if right heart catheterization done, cardiac output) • Pulmonary function tests if pulmonary disease present • Carotid duplex study in patients with a history of CVA, diabetes. or bruit on auscultation • Chest CT in patients undergoing redo operation to determine the relationship of the major blood vessels and cardiac chambers to the sternum.

CONCOMITANT ORGAN DYSFUNCTION

Cerebrovascular, renovascular, peripheral vascular disease, as well as COPD/emphysema

TREATMENT PREOPERATIVE PREPARATION Premedications

Midazolam or fentanyl can treat anxiety prior to transporting the patient to the OR and can be supplemented while placing the arterial line and other monitors. These medications should be carefully titrated, if at all, in patients with pulmonary hypertension, unstable angina, or heart failure. Special Concerns for Informed Consent

• Blood consent in the event of transfusion • Possibility of an intra-aortic balloon pump (IABP) post-CPB • Need for prolonged intubation • Explanation of possible postoperative complications

Antibiotics/Common Organisms

Third-generation cephalosporins and/or vancomycin within 60 minutes of incision (institution dependent) INTRAOPERATIVE CARE Choice of Anesthesia

General endotracheal anesthesia Monitors

• Standard ASA monitors, large bore IVs, and Foley catheters • Arterial line (beat-to-beat BP change, multiple lab work); typically placed preinduction • Central line access (preferably a 9 Fr sheath) for administration of fluids, vasoactive, and inotropic agents. It is also used to monitor central venous pressure (CVP) and float a Swan– Ganz if indicated • Transesophageal echocardiography to monitor myocardial function and assess volume status and diagnosis of any other cardiac pathology Induction/Airway Management

• Choice of induction agents depends on the patient’s hemodynamic status and comorbidities. A balanced anesthetic technique using small doses of a short-acting narcotic and etomidate is commonly used. In patients with significant LV dysfunction, higher doses of narcotics are often used. Neuromuscular blocking agents without vagolytic or histamine releasing effects are preferred; cisatracurium should be considered if there is impaired renal or hepatic function. • Inotropes may be started preinduction in patients with myocardial dysfunction and low EF in order to maintain hemodynamics. • Hemodynamic instability may require emergent “going on pump.”

Maintenance

• Balanced technique with volatile agents and short-acting narcotics facilitate early extubation. Volatile agents can cause peripheral vasodilatation and decrease myocardial contractility but can induce ischemic preconditioning and mitigate reperfusion injury (4). • “On pump.” After CPB is instituted, the patient is cooled and anesthetic requirement decreases. The perfusionist administers a low-dose volatile agent into the CPB circuit throughout the bypass period. Awareness typically occurs during rewarming when the anesthetic requirement increases and anesthesia is not properly supplemented. Additional doses of benzodiazepines, narcotics, or propofol should be considered when rewarming is initiated. Delivery of volatile agents from the anesthetic machine should be immediately restarted by the anesthesiologist after separation from CPB and resumption of ventilation. • Preparation for weaning. In anticipation of coming off bypass, adequate ventilation should be established and any metabolic and hematologic abnormalities need to be optimized. With warming, normal sinus rhythm will usually return; sometimes ventricular fibrillation will ensue, requiring defibrillation with internal pads at 10–20 J to revert to sinus rhythm. If the heart rate is <70 bpm, epicardial pacing wires should be considered.

Extubation/Emergence

• Most patients require some period of mechanical ventilation and inotropic support postoperatively. • In patients determined to be candidates for fast-tracking, it is better to use short-acting narcotics and neuromuscular blocking agents. Excluding factors include long bypass time, multiple comorbidities, complex procedures, hypothermia, coagulopathies, massive blood transfusion or volume resuscitation, or need for prolonged inotropic support.

FOLLOW-UP BED ACUITY

Intensive care unit (ICU) (preferably a cardiac unit) for ventilatory and inotropic support, as well as volume resuscitation, transfusion, urine output, and hemodynamic monitoring. ANALGESIA

• Pain on POD 1–2: Sternotomy incision; POD 3–7: Back pain, saphenous vein, or radial artery harvesting sites. • Narcotic PCA has shown to be effective, with eventual conversion to PO medications. • NSAIDs, tramadol, and paracetamol have been used adjunctively and shown to decrease the narcotic requirements (5). COMPLICATIONS

• Reoperation within 24 hours 7% • LV failure needing IABP or assist device 3–7% • MI 5% • Renal failure 3.5% • Stroke 3.1%

• Mediastinities 0.6%

PROGNOSIS

LIMA grafts have a 90–95% patency in 10 years. Patency for radial artery and SVGs are 85– 90% and 75%, respectively.

REFERENCES

1. LU M, Chen JJ, Awan O, et al. Evaluation of bypass grafts and stents. Radiol Clin N Am. 2010;48:757–770.

2. Mangano DT, et al. Cardiovascular morbidity and CABG surgery-a perspective; Epidemiology, cost and potential therapeutic solutions. J Card Surg. 1995;10(Suppl):366– 368.

3. Chaitman BR, Rosen AD, Williams DO, et al. The final 10-year follow-up, results from BARI randomized trial. J Am Coll Cardiol. 2007;49(15):1600–1606. 5. Zuagg M, Lucchinetti E, Spahn DR, et al. Volatile anesthetics mimic cardiac preconditioning by priming the activation of mitochondrial K(ATP) channels via multiple signaling pathways. Anesthesiology. 2002;97:4–14. 6. Konstantatos A, Silvers AJ, Myles PS. Analgesia best practice after cardiac surgery. Anesthesiol Clin. 2008;26:591–602.

ADDITIONAL READING

• Hensley FA, Martin DE, Gravlee GP, eds. A Practical Approach to Cardiac Anesthesia, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2008:230–260.

See Also (Topic, Algorithm, Electronic Media Element) • Cardiopulmonary bypass • Cardioplegia • Awareness under anesthesia

CLINICAL PEARLS

• Following anesthetic induction, if the patient becomes hemodynamically unstable, consideration to go onto pump should be emergently performed. • Fast-tracking extubation postoperatively should be considered whenever possible.

CORONARY ARTERY BYPASS GRAFTING, OFF-PUMP (OPCABG) Ali Salehi, MD

BASICS DESCRIPTION General

• The complications of cardiopulmonary bypass surgery (CPB) include a systemic inflammatory response that is associated with increased risk of stroke, perioperative myocardial infarction (MI), heart failure, and renal failure. • Off-pump coronary artery bypass grafting (OPCABG) dates back to the 1950s. Interest in the procedure has grown in North America since the 1990s. • Criteria for patients to be a candidate for OPCABG include the following: – Low ejection fraction (EF <30%) – Advanced pulmonary disease – Renal failure – Advanced aortic atherosclerosis – One or two vessel disease • The procedure begins similarly to on-pump cases: Incision, sternotomy, exposure of the heart and harvesting of graft conduits (left internal mammary artery (LIMA), saphenous vein, or radial artery), and anticoagulation with heparin. Heparin dosing (150–200 units/kg) and target activated clotting time (ACT; 250–300 seconds) are lower than with on-pump CABG. However, some surgeons prefer an ACT similar to on-pump CABG due to the potential for going on bypass. • An apical suction cup is used to position the heart for better exposure of the target coronary artery. An epicardial stabilizer is then applied to immobilize the area being anastomosed; it allows the heart to continue beating, but can cause regional myocardial dysfunction. • The LIMA to LAD anastomosis is usually done first because it does not require significant manipulation of the heart and restores blood flow to a significant portion of the left ventricle (LV). This may decrease the level of hemodynamic instability when the heart is positioned to perform the subsequent grafts (left circumflex and right coronary artery). The anastomosis is performed by incising the target artery and an intracoronary shunt is placed to maintain distal perfusion until completed. Close communication between the anesthesia team and the surgical team is essential at this time. • Heparin reversal. After the completion of revascularization, protamine (usually a dose of 50 mg) is given for heparin reversal. If the ACT is still elevated, small additional doses (20–30 mg) are given. • Shed blood is collected into a cell saver device, washed, and returned to the patient. • Epicardial pacing wires are placed. • Closure ensues after adequate hemostasis is achieved.

Position

• Supine, frog-legged, and arms tucked to the side • Prep from chin to toes (can cause considerable hypothermia) • Patient’s ankles, knees, and elbows need to be padded carefully to avoid nerve injury.

Incision

• Median sternotomy • Minimally invasive techniques through a thoracotomy (MIDCAB) and robotic-assisted procedures have also been performed, but are less common.

Approximate Time 4–6 hours

EBL Expected 300–600 cc

Hospital Stay

5–7 days on average; varies depending on comorbidities and complications Special Equipment for Surgery

• Sternotomy saw • Cardiopulmonary bypass machine (should be primed and ready if conversion is needed) • Different cannulae (possible need for CPB) • Off-pump retractor (allows attachment of apical suction and epicardial stabilizer) • Apical suction cup • Epicardial stabilizer • Cell saver

EPIDEMIOLOGY Morbidity

May have decreased length of stay and need for blood and blood product transfusion. Mortality

Similar to on-pump CABG

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Significant comorbidities may exist. • Manipulation and positioning of the heart can be associated with hemodynamic instability and arrhythmias. • Myocardial function should be monitored during the grafting period. • Maintenance of body temperature • Anesthetic technique should facilitate early extubation.

PREOPERATIVE ASSESSMENT

SYMPTOMS

• Can be asymptomatic and diagnosed during a routine check-up • Angina or angina equivalent, dyspnea, palpitations, fatigue, chest tightness, sweating, and epigastric discomfort History

• Detailed cardiac history and documentation of any recent changes. • Detailed neurological, renal, and pulmonary history due to the increased incidence of peripheral vascular, cerebrovascular, and renovascular comorbidities as well as smoking in this patient population. Signs/Physical Exam

• Tachycardia, hypotension, and hypertension • Congestive heart failure: Lower extremity swelling, jugular venous distention, and crackles in the lungs • Arrhythmias • Systolic ejection murmur due to ischemic mitral regurgitation or ruptured papillary muscle • Holosystolic murmur due to ischemic ventricular septal defect (VSD) • Pericardial friction rub • Due to post myocardial infarction pericarditis

MEDICATIONS

• Beta-blockers and statins should be continued into the perioperative period • Aspirin should be discontinued 3–5 days prior to surgery unless in high-risk patients (unstable angina, recent MI). • Clopidogrel should be discontinued 7–10 days prior to surgery, if possible. • ACE inhibitors. When taken on the day of surgery, there is a higher risk for hypotension at induction. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hgb/Hct, PT/INR/PTT • Electrolytes, BUN/creatinine • EKG (rhythm, heart block, bundle branch block, Q wave, ST-T changes, LV hypertrophy) • Echocardiogram (left and right ventricle function, wall motion abnormalities, valvular abnormalities, patent foramen ovale) • Coronary angiogram (extent of coronary involvement, other abnormalities, PA pressure if a right heart catheterization was done, cardiac output) • Pulmonary function tests in patients with pulmonary disease • Carotid duplex study in patients with a history of CVA, diabetes, or bruit on auscultation • Chest CT in patients undergoing redo operation to determine the relationship of the major blood vessels and cardiac chambers to the sternum CONCOMITANT ORGAN DYSFUNCTION

• Cerebrovascular disease • Renovascular disease • Peripheral vascular disease • COPD/emphysema

TREATMENT PREOPERATIVE PREPARATION Premedications

Midazolam or fentanyl can treat anxiety prior to transporting the patient to the OR and can be supplemented while placing the arterial line and other monitors. Should be carefully titrated, if at all, in patients with pulmonary hypertension, unstable angina, or heart failure. Special Concerns for Informed Consent

• Blood consent for possible need of transfusion • Possibility of placement of intra-aortic balloon pump perioperatively (preinduction to help stabilize hemodynamics) • Need for use of CPB due to hemodynamic instability • Need for prolonged intubation postoperatively due to the patient’s comorbidities • Explanation of possible postoperative complications

Antibiotics/Common Organisms

Third-generation cephalosporin and/or vancomycin within 60 minutes of incision (institution dependent) INTRAOPERATIVE CARE Choice of Anesthesia

General endotracheal anesthesia. Use of regional anesthesia for OPCABG has been reported, but is not popular with many anesthesiologists (4).

Monitors

• Standard ASA monitors • Large bore IVs • Foley catheter to monitor urine output • Arterial line (beat-to-beat BP change, multiple lab work). Often placed preinduction. • Central line access (preferably a 9FR sheath) for administration of fluids and vasoactive and inotropic agents. It is also used to monitor CVP and float a Swan–Ganz, if indicated (left heart failure, hemodynamic instability, and pulmonary hypertension). • Transesophageal echocardiography to monitor myocardial function, assess volume status, and diagnose other cardiac pathology. Most sensitive monitor to detect new regional wall motion abnormalities or worsening of mitral regurgitation during cardiac positioning and grafting. These changes are warning signs of an impending cardiovascular collapse. Induction/Airway Management

• Choice of induction agents depend on the patient’s hemodynamic status and comorbidities. A balanced anesthetic technique using small doses of a short-acting narcotic and etomidate is commonly used; in patients with significant LV dysfunction, higher doses of narcotics are often used. Neuromuscular blocking agents without vagolytic or histamine releasing effects are preferred; cisatracurium should be considered if there is impaired renal or hepatic function. • Inotropes may be started preinduction in patients with myocardial dysfunction and low EF in order to maintain hemodynamics.

Maintenance

• Balanced technique with volatile agents and short-acting narcotics (facilitate early extubation). Volatile agents can cause peripheral vasodilatation and decrease myocardial contractility but can induce ischemic preconditioning and mitigate reperfusion injury. • Hemodynamics. Manipulation and turning of the heart to access the coronaries can result in profound hypotension. This effect may be decreased by correcting all metabolic and electrolyte abnormalities; maintaining euvolemia by administering fluids or blood if Hgb <8 mg/dL; administering inotropes and vasopressors to support myocardial function and maintain myocardial perfusion, especially in patients with a low EF; and decreasing the heart rate to provide a quiet operating field (70–80 bpm). • Temperature. In the absence of CPB, warming can be difficult. Consider warming the operating room before patient arrival. Cover the patient during line placement and induction. All fluids should be administered via a hotline. Sterile forced-air warming blankets can be placed on the lower extremity after vein harvest grafting.

Extubation/Emergence

Patients can be extubated in the operating room or early in the intensive care unit (ICU). The decision should be made after a discussion between the surgeon and the anesthesiologist. Factors determining the feasibility of early extubation are normal LV function, little or no inotropic support, no evidence of bleeding, limited volume resuscitation, normothermia, hemodynamic stability, and a normal airway

FOLLOW-UP BED ACUITY

• ICU bed for ventilator and inotropic support as well as volume resuscitation, transfusion, urine output, and hemodynamic monitoring. • Length of ICU stay could be very short for uncomplicated cases.

ANALGESIA

Same as on-pump CABG COMPLICATIONS

Same as on-pump CABG PROGNOSIS

• Outcome studies have shown that there is decreased enzyme release, bleeding, atrial fibrillation, length of hospital stay, as well as the need for blood and product transfusion (avoiding the systemic inflammatory response) (1,3). • However, studies have not shown a difference in 30-day risk of death, stroke, MI, renal failure, mediastinitis, or coma (1,3). • There was no difference in neuropsychological outcome (1). • One-year outcomes showed that saphenous graft patency is worse for off-pump, while LIMA graft patency is the same (1,4). • Off pump coronary artery bypass grafting in comparison to on pump CABG tend to have fewer planned grafts completed (1).

REFERENCES

1. hroyer AL, Grover FL, Hattler B, et al. On-pump versus off-pump coronary artery bypass surgery. N Engl J Med. 2009;361(19):1827–1837. 2. ijeysundera DN, Beattie WS, Djaiani G, et al. Off-pump coronary artery surgery for reducing mortality and morbidity; meta-analysis of randomized and observational studies. J am Coll Cardiol. 2005;46:872–882. 3. Puskas JD, Williams WH, Mahoney EM, et al. Off-pump versus conventional coronary artery bypass grafting: Early and one year graft patency, cost and quality of life outcomes: A randomized trial. JAMA. 2004;291:1841–1849. 4. Bainbridge D, Cheng DCH. Minimally invasive direct coronary artery bypass and off-pump coronary artery bypass surgery: Anesthetic considerations. Anesthesiology Clin. 2008;26:437–452.

ADDITIONAL READING

• Hensley FA, Martin DE, Gravlee GP, ed. A Practical Approach to Cardiac Anesthesia, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2008:230–260.

See Also (Topic, Algorithm, Electronic Media Element) • Coronary artery bypass on pump

CLINICAL PEARLS

• Off bypass CABG decreases the systemic inflammatory response that is associated with bypass as well as other complications. Studies have shown a decrease in blood transfusion frequency, length of hospital stay, and bleeding. • However, 30-day outcome data has not shown an improvement in several parameters at this time.

CORONARY ARTERY DISEASE Brian L. Marasigan, MD

BASICS DESCRIPTION

• Coronary artery disease (CAD) is the presence of hardened and narrowed coronary arteries. This architectural change is often the result of atherosclerosis, which describes the buildup of plaque and cholesterol over years. Rare cases of genetic abnormality such as familial hypercholesterolemia can result in CAD prior to age 40 years. • CAD is the most common cause of ischemic heart disease, which is the leading cause of death in the US. • The spectrum of disease varies, and treatment should be tailored to symptoms and disease distribution. EPIDEMIOLOGY Incidence

Increasing as healthcare availability, imaging techniques, and average life expectancy increase. Prevalence

1–1.5% of the total US population has ischemic heart disease. Morbidity

• Ischemic cardiomyopathy (ICM) is the most common consequence of CAD. • The TIMI (Thrombolysis in Myocardial Infarction) risk score looks at 7 factors to determine risk. – Age 65 years or older – At least 3 risk factors for coronary artery disease – Prior coronary stenosis of 50% or more – ST-segment deviation on electrocardiogram at presentation greater than 0.5 mm – At least 2 anginal events in prior 24 hours – Use of aspirin in prior 7 days – Elevated serum cardiac markers As determined by number of risk factors, risk of all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization within the first 2 weeks are: 1 = 5%, 2 = 8%, 3 = 13%, 4 = 20%, 5 = 26%, 6/7 = 41% Mortality

Ischemic heart disease is the leading cause of death in the US. ETIOLOGY/RISK FACTORS

• Age: Males >45 years and women >55 years • Family history • High levels of LDL cholesterol • Low levels of HDL cholesterol • Hypertension (HTN) • Diabetes • Cigarette smoking • Obesity • Sedentary lifestyle • Type A personality • Postmenopausal • High lipoprotein A levels • Other diagnosed vascular diseases

PATHOPHYSIOLOGY

• Plaques consist of fat, cholesterol, calcium, white blood cells, and fibrin that cause arterial hardening. • Laminar flow within an artery is directly proportional to vessel radius to the fourth power; therefore, narrowing of arteries with plaque can significantly decrease blood flow. • The LV is more prone to ischemia than the right ventricle due to its thicker muscle and increased afterload that results in decreased oxygen delivery and increased oxygen consumption, respectively. When “stressed” from increases in heart rate, contractility, afterload, or preload, ischemia may result due to the impaired oxygen supply. • Ischemic cardiomyopathy (ICM) results from chronic hypoxia of the myocardium. Hypoxic events cause tissue damage and scar tissue formation and can significantly reduce pump function (decreased CO and ejection fraction). Arrythmia and angina are common at late stages of ICM. • Infarction can occur from myocardial oxygen supply–demand imbalance even without total coronary artery occlusion. Commonly, plaque buildup causes near occlusion of coronaries, but plaque disruption causes thrombus formation which more often leads to sudden cardiac death (SCD).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperative evaluation is aimed toward assessing current myocardial function and myocardium at risk for ischemia. • Anesthesia and surgery can impair myocardial oxygen supply and delivery. The anesthesia provider’s primary aim should be to maintain CO, coronary perfusion, and prevent cardiac decompensation.

PREOPERATIVE ASSESSMENT SYMPTOMS

• May be asymptomatic for decades as plaque builds up • Shortness of breath, dyspnea on exertion, fatigue, angina, palpitations, lightheadedness

History

Family history, previous diagnosis of CAD, risk factors Signs/Physical Exam

Congestive heart failure

TREATMENT HISTORY

• Previous cardiac evaluation • Angioplasty, stent placement (bare metal versus drug eluting) • Coronary artery bypass

MEDICATIONS

• Aspirin • Beta-blockers (first-line therapy) • Calcium channel blocker • Omega-3 fatty acids • Statin therapy • Antihyperglycemics and insulin

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Preoperative labs are based on type of surgery, medications, severity of CAD. • Diagnosis of CAD requires imaging: coronary angiogram, radionucleotide perfusion scans, magnetic resonance imaging. • Computed tomography (4).

CONCOMITANT ORGAN DYSFUNCTION

Atherosclerosis of the aorta, carotid artery, and peripheral arteries is common. CIRCUMSTANCES TO DELAY/ CONDITIONS

• Unstable angina • Severe disease without recent evaluation or appropriate medical management • Recent MI or stroke

CLASSIFICATIONS

TIMI grade flow is a widely adopted scoring system from 0–3 referring to levels of coronary blood flow assessed during percutaneous coronary angioplasty: • TIMI 0 flow (no perfusion) refers to the absence of any antegrade flow beyond a coronary occlusion. • TIMI 1 flow (penetration without perfusion) is faint antegrade coronary flow beyond the occlusion, with incomplete filling of the distal coronary bed. • TIMI 2 flow (partial reperfusion) is delayed or sluggish antegrade flow with complete filling of the distal territory. • TIMI 3 flow (complete perfusion) is normal flow that fills the distal coronary bed completely.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Midazolam to prevent anxiety and increased sympathetic tone, as needed • Narcotics for sympathetic stability and pain control, as needed • Patients on beta blockers should have their doses continued in the perioperative period.

Special Concerns for Informed Consent • Risk for intraoperative MI and SCD • Risk for transfusion • Invasive monitoring

INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on surgical procedure and patient preference • If possible, MAC is preferred (less expected hemodynamic perturbations) • If a neuraxial technique is chosen, aspirin does not contraindicate placement

Monitors

• Standard ASA monitors • 5-lead EKG has increased sensitivity for LV ischemia. • Arterial line allows beat-to-beat BP monitoring or minimally invasive CO monitoring. • Central venous line may be considered to guide fluid administration and for fluid and/or vasopressor delivery. • Pulmonary artery catheter may be considered if the patient is at high risk for decompensation to monitor right and LV function, volume status, cardiac output, and mixed venous saturation • Transesophageal echocardiography may be considered for hypertrophic cardiomyopathy and management of perioperative events. • Newer noninvasive CO monitors – NICOMs based on bioimpedance or bioreactance.

Induction/Airway Management

• Smooth, controlled induction to maintain vital signs and coronary perfusion within normal limits. • Narcotic-based inductions may have a more gradual and minimal impact on BP and cardiac function, and may be preferable to the potentially harsher sedative-hypnotic only inductions. • Short-acting medications should be available to treat increases in heart rate (esmolol), HTN (esmolol, nitroglycerin, calcium channel blockers, propofol), and hypotension (phenylephrine, ephedrine). Maintenance

• Volatile and/or IV anesthetics may be used; neither technique has shown superiority in

patients with coronary artery disease. • Maintaining myocardial oxygen supply and decreasing demand are more important than the specific anesthetic technique. – Decrease the heart rate, while maintaining an adequate cardiac output. – Monitor and maintain normal sinus rhythm – Decrease contractility while maintaining adequate cardiac output; avoid and anticipate sympathetic stimulation (e.g., incision, retraction, pain, adequate depth of anesthesia) with narcotics and/or deepening the anesthetic – Optimize the afterload; an adequate diastolic perfusion pressure is necessary to maintain cardiac perfusion (CPP = DBP–LVEDP). However, increases in afterload require an increase in myocardial oxygen consumption – Optimize preload; an adequate intravascular fluid volume is necessary to maintain an adequate stroke volume (Starling curve). – Maintain the oxygen content of arterial blood with an adequate hematocrit, oxygen saturation, and ventilator settings. – Alternatively, support life in severe systolic dysfunction with inotropes and vasopressors as needed. • Normothermia. Measures to avoid hypothermia should be made; shivering can increase myocardial oxygen consumption significantly • Intraoperative ischemia should be monitored and treated utilizing the coordinated efforts of the healthcare team, so as to optimize myocardial oxygen supply and demand.

Extubation/Emergence

Have narcotics, anxiolytics, antihypertensives, and beta-blockers available to maintain postoperative vital sign stability

POSTOPERATIVE CARE BED ACUITY

Depends on type of surgery and intraoperative events MEDICATIONS/LAB STUDIES/CONSULTS

• Cardiology consult may be warranted depending on perioperative cardiac events • Medicine consult for the management of diabetes, hyperlipidemia, HTN, and diet control

COMPLICATIONS

• Perioperative arrhythmia • MI • Death

REFERENCES

1. Antman EM, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. 2000;284(7):835–842. 2. Shehata N, et al. Factors affecting perioperative transfusion decisions in patients with

coronary artery disease undergoing coronary artery bypass surgery. Anesthesiology. 2006;105(1):19–27. 3. Kulka PJ, et al. Coronary artery plaque disruption as cause of acute myocardial infarction during cesarean section with spinal anesthesia. J Clin Anesth. 2000;12(4):335–338.

4. Rodríguez-Palomares JF, et al. Coronary angiography by 16-slice computed tomography prior to valvular surgery. Rev Esp Cardiol. 2011; 64(4):269–276. 5. Ogata T, et al. Morphological classification of mobile plaques and their association with early recurrence of stroke. Cerebrovasc Dis. 2010;30:606–611.

ADDITIONAL READING

• World Health Organization Department of Health Statistics and Informatics in the Information, Evidence and Research Cluster (2004). The global burden of disease 2004 update. Geneva: WHO. • http://www.timi.org/ See Also (Topic, Algorithm, Electronic Media Element) • Cardiac output methods to measure • Myocardial oxygen demand • Postoperative chest pain • Coronary stents

CODES ICD9 • 414.00 Coronary atherosclerosis of unspecified type of vessel, native or graft • 414.01 Coronary atherosclerosis of native coronary artery ICD10 • I25.10 Athscl heart disease of native coronary artery w/o ang pctrs • I25.110 Athscl heart disease of native cor art w unstable ang pctrs

CLINICAL PEARLS

• CAD is commonly caused by atherosclerosis. • Severity of CAD must be confirmed by imaging studies and symptomatology. Multiple classifications exist for atheroma that mitigates management. • Previous stent placement may place the patient under increased risk for intraoperative ischemia due to stress or inadequate antiplatelet treatment; especially within 4–6 weeks of bare-metal stent and 1 year with DES. • Decreasing myocardial oxygen demand and increasing myocardial oxygen supply are the key principles of management. • Acute or chronic functional decompensation must be supported with inotropes and vasopressors when necessary, even if they cause increased myocardial oxygen consumption.

CORONARY ARTERY SPASM (PRINZMETAL ANGINA) Victor L. Mandoff, MD

BASICS DESCRIPTION

• Coronary artery spasm (CAS) describes vasospasm of the coronary arteries that can manifest clinically as angina, arrhythmias, acute myocardial infarction, or sudden death. • Typically it occurs – In a cyclical pattern – In clusters with symptom free quiescent episodes in between – At rest – After midnight to early morning • It was first described by Dr. Myron Prinzmetal in 1959 as episodes of “temporary increased tonus” (1) and is thus commonly referred to as Prinzmetal angina (also variant angina).

EPIDEMIOLOGY Incidence

Observed in 4 out of 100 (4%) of patients undergoing cardiac angiography in the US. Prevalence

• Patients are usually in their 50s • Some studies suggest that it is more common in females • People of Japanese ethnicity have a three-fold increase over Caucasians.

Morbidity

Acute myocardial infarction has been shown to occur in 3.5–6.5% of patients with a diagnosis of CAS. Mortality

• Prognosis depends on coexisting atherosclerotic disease. One-year survival in patients: – Without atherosclerotic disease or with single vessel disease: 99% – With multivessel atherosclerotic disease: 87% ETIOLOGY/RISK FACTORS

• More common in patients with the following comorbidities: • Smokers • Diabetes mellitus • Hypercholesterolemia • Migraine headaches • Raynaud’s disease • Cocaine users

• Can be triggered by administration of ergonovine, histamine, serotonin, and acetylcholine (ACh) • Anxiety or panic disorder • Type A personality • East Asian populations

PATHOPHYSIOLOGY

• Although the clinical manifestations of variant angina are similar to those of classical angina (secondary to an imbalance in myocardial oxygen supply and demand), their pathogenesis and treatment differ. Coronary spasm is an abnormal contraction of an epicardial coronary artery, as opposed to plaque buildup or rupture (acute coronary syndrome). • The exact mechanism is not completely understood and multiple theories exist that revolve around vascular endothelial function combined with an increase in vascular smooth muscle abnormalities and oxidative stress. • Dysfunctional coronary artery endothelium. The endothelium normally plays an important role in vascular tone regulation. Dysfunction is characterized by an impairment of the balance between endothelium-derived relaxing factors and endothelium-derived constricting factors (2). • Hypercontractile response to ACh and intracellular calcium. ACh’s normal vasodilatory effects appear to be impaired in the face of endothelial dysfunction, causing vasoconstriction instead. Calcium’s effect may be the result of increased smooth muscle cell mass and/or abnormalities in the Rho-kinase pathway. • Increased oxidative stress. Smoking and insulin resistance have been shown to decrease nitric oxide (NO) activity via oxygen-derived free radicals; this effect appears to be diminished with antioxidants such as Vitamin E. • Enhanced phospholipase C activity

ANESTHETIC GOALS/GUIDING PRINCIPLES

• In patients with known CAS, avoid hyperventilation and histamine releasing drugs. Continue perioperative calcium channel blockers and avoid nonselective beta-blockers. • As with coronary artery disease (CAD), optimize coronary perfusion pressure, avoid tachycardia, maintain normal sinus rhythm, and optimize preload, afterload, and contractility.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Retrosternal pain or pressure • Radiation to the neck, jaw, left arm, or left shoulder • Can be associated with a loss of consciousness or arrhythmias • Shortness of breath

History

• May describe anginal pain typically at rest in clusters of two or three • Occurs between midnight and early morning

• Resolves spontaneously or with nitroglycerin

Signs/Physical Exam

• May be absent between episodes • No real pathognomonic sign • Hypertension • Tachycardia • Transient arrhythmia or heart murmur • Rales • Jugular venous distension • Peripheral edema

TREATMENT HISTORY

Coronary stenting may be performed in patients that are refractory to medical management. Appears to be more effective when focal CAS, as opposed to multivessel spasm. MEDICATIONS

• Nitrates include short-acting nitroglycerin and long acting isosorbide dinitrate. • Calcium channel blockers such as amlodipine, nifedipine, diltiazem, and verapamil • Selective beta-blockers are beneficial if there is coronary atherosclerotic stenosis. Nonselective blockers can exacerbate spasm by inhibiting beta-mediated vasodilation, unmasking alpha-adrenergic tone, and increasing vascular permeability to calcium. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• No specific labs are indicated preoperatively. May consider a CBC if anemia or infection are suspected and electrolytes if diabetic or with renal disease. • EKG. Baseline EKGs are commonly normal. During acute episodes, ST segment elevation is more commonly seen than ST depression (which is more common in CAD). May resolve completely when the patient is asymptomatic; however, T wave inversion has been shown to persist for hours and even days (1). Heart block is associated with CAS of the right coronary artery, whereas ventricular tachycardia is associated with CAS of the left anterior descending artery. • Initial workup of patients may have involved nuclear stress tests, Holter monitoring, treadmill or echocardiogram stress testing, and coronary angiography. Angiography is considered the gold standard and agents and techniques that induce spasm may have been utilized (hyperventilation, ACh, ergonovine, methylergonovine). CONCOMITANT ORGAN DYSFUNCTION

• Coronary artery disease • Pulmonary disease in smokers • Vasospastic disorders: Raynaud phenomenon and migraines

CIRCUMSTANCES TO DELAY/ CONDITIONS

• In patients with known or undiagnosed disease, elective cases should be delayed in the

event of an active anginal attack preoperatively. • Diagnosed disease. Symptoms should resolve (angina, arrhythmias), maneuvers to improve myocardial oxygen supply while decreasing demand should be implemented, and assessment of cardiac function may be considered. • Undiagnosed disease. The presentation of new onset anginal pain, particularly with EKG changes and arrhythmias will require further cardiac workup (echocardiogram, stress testing, cardiology consult).

TREATMENT PREOPERATIVE PREPARATION Premedications

• Confirm that regular cardiac medications including nitrates, calcium channel blockers, and beta-blockers are taken; if not, consider administering PO or an IV dose. • Anxiolytics as needed

Special Concerns for Informed Consent

• May be at a higher risk for intraoperative and postoperative cardiac events, especially if there are pre-existing coronary lesions. • Explain the risks and benefits of invasive monitors • Explain the possibility of postoperative admission to stepdown, telemetry, or intensive care unit. INTRAOPERATIVE CARE Choice of Anesthesia

• Regional, general anesthesia, and deep sedation have all been used. Choice should consider the surgical procedure, as well as patient comorbidities and preferences. • Deep sedation may have the benefits of decreased hemodynamic changes.

Monitors

• Standard ASA monitors • Additional monitors are used based on patient risk factors (congestive heart failure, previous myocardial infarction, hypertension, arrhythmias, diabetes mellitus, smoking, etc.) along with the surgical procedure. Induction/Airway Management

Guided by patient’s medical condition, airway difficulty, and risk for aspiration. Goals should include a slow controlled induction and avoidance of hyperventilation with bag mask ventilation. Maintenance

• Balanced anesthetic combining narcotics with volatile or IV agents. No specific technique has been shown to be superior. • Avoid hyperventilation as this may evoke spasm intraoperatively.

• Optimize myocardial oxygen supply and demand. • Maintain normothermia; hypothermia may be a trigger for vasospasm. • Intraoperative EKG changes. In patients with known disease, the onset of ST segment elevation or arrhythmias may indicate coronary spasm. Treatment may include the following: • IV administration of nitroglycerin, calcium channel blockers, and magnesium • Increasing the PaCO2

• Other supportive measures for hypotension, tachycardia, arrhythmias, or congestive heart failure (if applicable). Extubation/Emergence

• When extubation criteria are met • Reversal of muscle relaxant can theoretically lead to a Prinzmetal angina attack if ACh is a known trigger.

POSTOPERATIVE CARE BED ACUITY

Depends on the surgical procedure, comorbidities, and intraoperative events such as myocardial ischemia or arrhythmias. MEDICATIONS/LAB STUDIES/CONSULTS

• EKG • Serial cardiac enzymes if intraoperative ischemia was seen. • Cardiology consult depends on complications intraoperatively or postoperatively.

COMPLICATIONS

• Arrhythmias • Myocardial ischemia

REFERENCES

1. Ajani AE, Yan BP. The mystery of coronary artery spasm. Heart Lung Circ. 2007;16(1):10– 15. 2. Kawano H, Node K. The role of vascular failure in coronary artery spasm. J Cardiol. 2011;57:2–7. 3. Wang SS. Coronary artery vasospasm. Emedicine. 2011:1–16. 4. Massie BM, Amidon TM. Heart. Current Medical Diagnosis & Treatment. 2002:387–398.

ADDITIONAL READING

• ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery. See Also (Topic, Algorithm, Electronic Media Element)

• Raynaud’s syndrome • Chronic angina • Smoking

CODES ICD9

413.1 Prinzmetal angina ICD10

I20.1 Angina pectoris with documented spasm

CLINICAL PEARLS

• CAS remains a diagnosis of exclusion; therefore intraoperative presentation may be misdiagnosed initially for ischemia or infarction secondary to hemodynamic imbalance, or plaque rupture, respectively.

CORONARY STENT Zdravka Zafirova, MD

BASICS DESCRIPTION

• Atherosclerotic coronary artery disease (CAD) results in luminal narrowing and thrombosis leading to coronary perfusion impairment • Percutaneous coronary intervention (PCI) revascularization is performed to restore arterial patency and improve myocardial perfusion • Stent deployment has been shown to improve long-term arterial patency (1)[B], but is limited by restenosis and thrombosis. And although ischemic symptoms are improved and the need for repeat intervention is reduced, a decrease in mortality has not been clearly demonstrated. • The two currently available stents are: – Bare metal stents (BMS) – Drug-eluting stents (DES) EPIDEMIOLOGY Prevalence

• Stent restenosis (lifetime) – BMS: 10–67% – DES: 0–11% • Stent thrombosis – Lifetime: BMS 0.6–3.5%, DES 1.2–3.6% – Within 1 month (early): BMS 0.1–0.6%, DES 0.5–1% – 1–12 months (late): BMS 0.1–1.3%, DES 0.1–0.9% – >12 months (very late): BMS 0–2.1%, DES 0.6–2.8%

Prevalence

• Stent use in PCI: 85–95% • Although the use of DES have decreased due to concerns for stent thrombosis (2)[B], it is still used 75% of the time.

Morbidity

• Stent restenosis presents with angina symptoms, acute coronary syndrome (ACS), and myocardial infarction (MI). DES have a lower rate of restenosis and need for repeat revascularization • Stent thrombosis often presents as ACS/MI (50–70%). The overall rate of stent thrombosis is similar in DES and BMS; however, DES require a longer duration of dual antiplatelet therapy (DAT) • Stent fracture

• Native CAD

Mortality

• Similar rate between DES and BMS • Stent thrombosis carries a 10–45% mortality

ETIOLOGY/RISK FACTORS

• Risk factors for CAD: Atherosclerosis, hypertension, diabetes mellitus (DM), end-stage renal disease, hypercholesterolemia, smoking, hyperhomocysteinemia, genetic factors • Risk factors for stent thrombosis – Patient factors: Premature discontinuation of DAT, DM, low ejection fraction, renal failure, advanced age. – Lesion factors: Small vessels, multiple lesions, long or overlapping stents, bifurcations, suboptimal stent results

PHYSIOLOGY/PATHOPHYSIOLOGY

• Coronary artery stenting is performed to hold vessel walls open following balloon angioplasty. Following dilation, the artery wall is prone to weakening and collapse, as well as restenosis (neointimal hyperplasia); stents were developed to provide a mechanical framework or scaffold. • BMS. An expandable metal stent was initially developed and utilized; and although collapse was decreased, in-stent restenosis was observed in 25% of patients at 6 months. • DES. Developed in response to the problem of BMS restenosis. Expandable metal stents were coated with a polymer that allowed time-release of drugs into the arterial wall. Drugs such as sirolimus, paclitaxel, and everolimus possess antiproliferative and immunosuppressive properties that impair endothelialization and consequently neointimal hyperplasia (restenosis). However, in doing so, the denuded vessel walls do not heal and the stent, a foreign body, remains exposed to the circulation; this can result in clot formation and thrombosis. To decrease this occurrence, antiplatelet therapy is required for longer periods than with BMS.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The risk and benefits of the procoagulant perioperative state versus the risk of bleeding from antiplatelet agents need to be weighed; may require a discussion with the cardiologist and surgeon • Premature interruption of antiplatelet therapy should be avoided, if at all possible. When necessary, discuss perioperative anticoagulant management with the cardiologist and surgeon. • Optimization of myocardial oxygen delivery and control of oxygen consumption

PREOPERATIVE ASSESSMENT SYMPTOMS

• Angina or anginal equivalents: Chest pain, dyspnea, nausea, and vomiting – Stable versus unstable (progressive increase in the frequency and duration of the

symptoms, unresolving symptoms, and symptoms at rest)

History

• Stent type: BMS or DES • Placement date: <1 month, 1–12 months, or >12 months • Ischemic events pre-stent and post-stent; type, resolution, recurrence.

Signs/Physical Exam

• Tachycardia, arrhythmias • Hypotension, congestive heart failure, shock • Pallor, diaphoresis • Tachypnea, hypoxia

TREATMENT HISTORY

• Antiplatelet therapy: Single, dual (DAT), or triple therapy. Duration (3)[A]: – BMS require at least 1 month of DAT, followed by aspirin (ASA) – DES require at least 12 months of uninterrupted DAT, followed by ASA

Medications

• Aspirin • Thienopyridines: Clopidogrel, ticlopidine, prasugrel. Determine length of discontinuation • intravenous (IV) glycoprotein (GP) IIb/IIIa inhibitors • Anticoagulants • Proton pump inhibitors (PPI) used to prevent or treat gastroesophageal acid and reflux disorders may attenuate the effects of the antiplatelet agents. This may be an effect of the individual agent rather than the class of drugs • Beta-adrenergic antagonists • hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) • Antihypertensive medications • Diuretics • Antiarrhythmic agents

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Recent 12 lead ECG – Comparison with old one to evaluate for disease progression – As a baseline study for comparison when evaluating perioperative ECG abnormalities indicative of acute coronary event • Cardiac stress test may be indicated as a part of the preoperative evaluation for new or unresolved symptoms of CAD since the revascularization, or limited exercise tolerance (<4 metabolic equivalents). • Angiography evaluation of – New symptoms – Stent patency – Abnormal stress test

CONCOMITANT ORGAN DYSFUNCTION

• Cerebrovascular disease • Hypertension • Renal failure • Bleeding abnormalities due to antiplatelet agents • Gastrointestinal (GI) abnormalities: Bleeding, peptic ulcer disease

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Elective surgery should be delayed – >1 month after ACS or stent placement – If interruption of DAT is necessary for the surgery, it should be delayed until >1 month for BMS and >12 months for DES – In patients who have discontinued the minimum antiplatelet therapy duration following stenting, in order to restart antiplatelet therapy.

CLASSIFICATIONS

• Stent type – BMS – DES First-generation DES stents have a stainless steel construction Newer generation have thinner, stronger cobalt chromium, and more biocompatible polymers

TREATMENT PREOPERATIVE PREPARATION Premedications

• Continue antiplatelet therapy as indicated – DAT continuation may be appropriate in cases where the risk of bleeding is low – Reduced dose of antiplatelet agent may be used (e.g., ASA 81 mg) – Transition to a single agent for 7 days before the procedure, if the risk of bleeding on DAT is significant – Parenteral platelet inhibitors: IV IIb/IIIa inhibitor and/or unfractionated heparin infusion may be used if premature enteral DAT interruption is necessary. Both should be discontinued the night before surgery. – Anticoagulants are not an effective substitute for antiplatelet agents in preventing stent thrombosis. • H2-blockers should be considered instead of PPI • Beta-adrenergic antagonists should be continued in the perioperative period; consider initiation of therapy in appropriate patients. Special Concerns for Informed Consent

• Risk of stent thrombosis, especially if premature interruption of antiplatelet therapy is

necessary. • Risk of bleeding as a result of perioperative antiplatelet therapy.

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia versus regional anesthesia: Evaluation of benefits and risks of each modality • The bleeding risk of regional anesthesia due to antiplatelet therapy should be considered and discussed with the patient and the surgeon (4)[C]. Monitors

• Continuous ECG monitoring with ST segment analysis in diagnostic mode • Invasive hemodynamic monitoring may be considered based on comorbidities and surgical procedure.

Induction/Airway Management

• A slow, controlled induction should be performed to maintain adequate oxygen delivery and supply during airway manipulation. • If a rapid sequence induction is being considered, it should be weighed against the patient’s risk for myocardial ischemia.

Maintenance

• A balanced anesthetic with volatile and/or IV agents. No one technique has shown superiority in patients with coronary stents or CAD. • Ischemia and infarction may be suspected from EKG abnormalities (T waves inversions, premature ventricular contractions, ST depression or elevation). Hypotension and cardiovascular collapse may result from ACS. Treatment may include the following: – Discontinuing the surgery and stimulation while stabilizing the patient, if possible. – Intraoperative echocardiogram – Increasing myocardial oxygen supply and decreasing demand – Anticoagulation/antiplatelet agents – Emergency balloon pump, PCI, or coronary artery bypass

Extubation/Emergence

• Support of hemodynamic stability and oxygen delivery • Pain control • Attenuation of stress response with adequate pain control, heart rate control, and antihypertensive medications

FOLLOW-UP BED ACUITY

Care in a telemetry or intensive care setting may be indicated based on the following: • Preoperative risk stratification

• Premature antiplatelet therapy discontinuation • Perioperative events

MEDICATIONS/LAB STUDIES/CONSULTS

• Reinstitution of antiplatelet therapy (preoperative regimen) as soon as surgical bleeding risk is decreased. A bolus dose of antiplatelet agent may be considered. • Monitoring for coronary ischemia with EKG, cardiac enzymes as indicated. • Cardiology consult may be indicated

COMPLICATIONS

• Stent thrombosis: Very high mortality rate • Bleeding: Rarely significant with aspirin only, increases with antiplatelet therapy, and highest risk with DAT. Severity depends on the surgical procedure (location and extent). Although posterior eye chamber and neurosurgical procedures demonstrate an increase in morbidity and mortality, many procedures do not (e.g., CABG, vascular, orthopedic, and urological). There may be an increase in transfusion rate with continued antiplatelet therapy.

REFERENCES

1. Kirtane AJ, Gupta A, Iyengar S, et al. Safety and efficacy of drug-eluting and bare metal stents: Comprehensive meta-analysis of randomized trials and observational studies. Circulation. 2009;119:3198–3206. 2. Anwaruddin S, Askari AT, Saudye H, et al. Characterization of postoperative risk associated with prior drug-eluting stent use. JACC Cardiovasc Interv. 2009;2:542–549. 3. Tanzilli G, Greco C, Pelliccia F, et al. Effectiveness of two-year clopidogrel+aspirin in abolishing the risk of very late thrombosis after drug-eluting stent implantation (from the TYCOON [two-year ClOpidOgrel need] study). Am J Cardiol. 2009;104:1357–1361. 4. Osta WA, Akbary H, Fuleihan SF. Epidural analgesia in vascular surgery patients actively taking clopidogrel. Br J Anaesth. 2010;104:429–432.

ADDITIONAL READING

• Grines CL, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: A science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians J Am Coll Cardiol. 2007;49:1–6. • Nordmann AJ, et al. Mortality in randomized controlled trials comparing drug-eluting vs. bare metal stents in coronary artery disease: A meta-analysis. Eur Heart J. 2006;27:2784– 2781.

See Also (Topic, Algorithm, Electronic Media Element) • Coronary artery disease • Intraoperative ischemia

• Cardiac catheterization • Unstable angina

CODES ICD9

414.00 Coronary atherosclerosis of unspecified type of vessel, native or graft ICD10 I25.10 Athscl heart disease of native coronary artery w/o ang pctrs

CLINICAL PEARLS

• Coronary stents improve the success of revascularization after PCI. However, stent thrombosis leads to significant morbidity and mortality. Thus, premature interruption of antiplatelet therapy should be avoided for elective surgical procedures.

CORTISOL

Joe C. Hong, MD

BASICS DESCRIPTION

• Cortisol is a steroid hormone of the glucocorticoid family that plays a vital role in the response to stress. In particular, cortisol – Stimulates gluconeogenesis – Suppresses inflammation – Maintains vascular responsiveness to catecholamines • Cortisol is synthesized and secreted by the adrenal cortex. It is regulated by adrenocorticotropic hormone (ACTH) produced by the anterior pituitary. ACTH is, in turn, regulated by corticotropin-releasing hormone (CRH) produced by the hypothalamus. Cortisol exerts negative feedback control by inhibiting the secretion of CRH and ACTH. • A 24-hour circadian rhythm causes oscillatory release of CRH, ACTH, and cortisol. For those who sleep at night, cortisol levels are highest just before waking and lowest in the evening. • Disease states include Cushing’s syndrome (glucocorticoid excess) and Addison’s disease (adrenocortical insufficiency). PHYSIOLOGY PRINCIPLES

• Cortisol is a steroid hormone that enters cells and binds to an intracellular cytoplasmic receptor. This bound complex stimulates DNA transcription resulting in protein production that mediates the effects of cortisol. • Cortisol stimulates gluconeogenesis: – Increases protein catabolism and decreases protein synthesis in the muscle, thereby providing more amino acids to the liver for gluconeogenesis. – Decreases insulin sensitivity and decreases glucose utilization in adipose tissue. – Lipolysis is increased, providing more substrate for gluconeogenesis. • Cortisol suppresses inflammation: – Inhibits the production of interleukin-2 and proliferation of T lymphocytes. – Inhibits release of histamine and serotonin from mast cells and platelets. – Decreases prostaglandin and leukotriene synthesis by inhibiting the formation of arachidonic acid. ANATOMY

• CRH-containing neurons are located in the paraventricular nuclei of the hypothalamus. CRH is released into the hypothalamic–hypophysial portal blood and delivered to the anterior pituitary where it stimulates ACTH secretion. • The anterior lobe of the pituitary synthesizes and secretes ACTH into the bloodstream under CRH stimulation. • Cortisol is produced by cells within the zona fasciculata of the adrenal cortex.

• The adrenal gland is composed of the inner medulla that produces catecholamines and the outer cortex that is divided into three histological zones. Going from outside inwards: The outer most zona glomerulosa is the source of aldosterone production. Just beneath is the zona fasciculata, the source of glucocorticoids production. The inner most layer of the cortex is the zona reticularis; responsible for the production of androgens.

DISEASE/PATHOPHYSIOLOGY

• Cortisol excess states (Cushing’s syndrome): – Caused by endogenous oversecretion or iatrogenic treatment with glucocorticoids at supraphysiologic doses. – Endogenous oversecretion. The majority of instances involve ACTH overproduction (80%). These disease states include ACTH producing pituitary adenoma and ectopic ACTH production from tumors such as small cell carcinoma of the lung and pancreatic carcinoma. ACTH-independent processes such as cortisol secreting adrenal adenoma or carcinoma make up the remainder of endogenous cortisol oversecretion (20%). – When the source of endogenous cortisol is caused by overproduction of ACTH by the pituitary, the condition is known as Cushing’s disease. – Chronic excess of glucocorticoids results in physical changes. These include central obesity, moon facies, purple striae, muscle wasting, osteopenia, hirsutism, and hyperpigmentation. Clinical signs include glucose intolerance hypertension, hypokalemic alkalosis, and leukocytosis. – Treatment of endogenous sources of excess glucocorticoid entails surgical resection. • Cortisol-deficient states: – Primary adrenocortical insufficiency is caused by the inability of adrenal glands to produce both glucocorticoids and mineralocorticoids (Addison’s disease). Most common cause is autoimmune destruction of the adrenal cortex resulting in acute adrenal crisis. Other causes of adrenocortical insufficiency include metastatic disease to the adrenal cortex, adrenal hemorrhage, infection of the adrenal gland (tuberculosis, opportunistic infections with HIV, fungemia), and amyloid infiltration [1]. Characterized by elevated ACTH levels but decreased levels of glucocorticoids and mineralocorticoids. Clinical features are related to the adrenocortical hormone deficiency. Hypoglycemia is caused by cortisol deficiency. Hypotension, postural hypotension, hyperkalemia, metabolic acidosis, and volume contraction are caused by mineralocorticoid deficiency. Hyperpigmentation is caused by elevated ACTH secretion. Other signs and symptoms include weakness, fatigue, lethargy, anorexia, nausea, abdominal pain, prerenal azotemia, hypercalcemia, convulsions, fever, and syncope. Treatment: Replacement of glucocorticoids (hydrocortisone, prednisone, methylprednisolone) and mineralocorticoids (fludrocortisone). – Secondary adrenocortical insufficiency is caused by decreased ACTH production by the anterior pituitary gland. Most common cause of secondary adrenocortical insufficiency is withdrawal of corticosteroid therapy. Other causes include pituitary tumor, pituitary surgery or radiation, postpartum hypopituitarism (Sheehan’s syndrome), and sarcoid infiltration of the pituitary gland.

Chronic corticosteroid therapy suppresses the hypothalamus and anterior pituitary resulting in decreased production of CRH and ACTH, respectively. Decreased levels of CRH and ACTH cause atrophy of the zona fasciculata, resulting in glucocorticoid deficiency. During times of physiologic stress, the patient is unable to acutely increase cortisol production, resulting in acute secondary adrenocortical insufficiency.

PERIOPERATIVE RELEVANCE

• Cortisol excess states: – Patients with Cushing’s syndrome must have their diabetes, BP, intravascular volume status, and electrolytes optimized prior to surgery. – The body habitus of Cushingoid patients (central obesity, moon facies, buffalo hump) may present an airway challenge. – A high cortisol state causes immunosuppression and poor wound healing. Sterile technique is vital for all procedures and line placements to minimize iatrogenic infections. – Careful positioning is vital as severe osteopenia increases risk of fractures. – Patients with adrenal Cushing’s syndrome presenting for adrenalectomy should receive hydrocortisone at the time of surgery as they are at risk of developing acute glucocorticoid deficiency postoperatively. Hydrocortisone can then be tapered as the previously quiescent contralateral adrenal gland resumes corticosteroid production. • Cortisol-deficient states: – Patients with adrenocortical insufficiency should continue their mineralocorticoid and glucocorticoid replacement therapy up until their time of surgery. Clinical features of overt deficiency include hyperkalemia, hyponatremia, metabolic acidosis, and myocardial conduction defects. – Hydrocortisone has both glucocorticoid and mineralocorticoid activity. Therefore, it is an ideal agent to use for the management of adrenocortical insufficiency. – Additional perioperative stress dose of glucocorticoids may be necessary as these patients may not be able to mount an adequate stress response. Traditional recommendation is 200 mg hydrocortisone per 70 kg body weight per day [2]. However, smaller doses of 100 mg per 70 kg body weight per day have been used with success [3,4]. – The amount of perioperative hydrocortisone supplementation is based on the anticipated stress of the procedure, relative degree of trauma, and the depth of anesthesia [5].

REFERENCES

1. Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med. 2003;139(3):194–204. 2. Symreng T, Karlberg BE, Kågedal B, et al. Physiological cortisol substitution of long-term steroid-treated patients undergoing major surgery. Br J Anaesth. 1981;53(9):949–954. 3. Glowniak JV, Loriaux DL. A double-blind study of perioperative steroid requirements in secondary adrenal insufficiency. Surgery. 1997;121(2):123–129. 4. Bromberg JS, Alfrey EJ, Barker CF, et al. Adrenal suppression and steroid supplementation in renal transplant recipients. Transplantation. 1991;51(2):385–390. 5. Lampe GH, Roizen MF. Anesthesia for patients with abnormal function of the adrenal

cortex. Anesthesiol Clin North Am. 1987;5:245.

ADDITIONAL READING

• Graham GW, Unger BP, Coursin DB. Perioperative management of selected endocrine disorders. Int Anesthesiol Clin. 2000;38(4):31–67. • Udelsman R, Ramp J, Gallucci W, et al. Adaptation during surgical stress: A reevaluation of the role of glucocorticoids. J Clin Invest. 1986;77(4):1377–1381.

See Also (Topic, Algorithm, Electronic Media Element) • Aldosterone • Acute adrenal insufficiency

CLINICAL PEARLS

• Patients with Cushing’s syndrome must have their diabetes, BP, intravascular volume status, and electrolytes optimized prior to surgery. They are at high risk for poor wound healing and surgical wound infection. • The body habitus of Cushingoid patients (central obesity, moon facies, buffalo hump) may present an airway challenge. • Patients with adrenal Cushing’s syndrome presenting for adrenalectomy should receive hydrocortisone at the time of surgery as they are at risk of developing acute glucocorticoid deficiency postoperatively. • Patients with adrenocortical insufficiency should continue their mineralocorticoid and glucocorticoid replacement therapy up until their time of surgery. Clinical features of overt deficiency include hyperkalemia, hyponatremia, metabolic acidosis, and myocardial conduction defects. • Acute withdrawal of exogenous glucocorticoids in the perioperative period may result in acute adrenocortical insufficiency.

CRANIOSYNOSTOSIS Ellen Y. Wang, MD

BASICS DESCRIPTION General

• Craniosynostosis is an abnormal, premature closure of one or more of the cranial sutures and can lead to an abnormally shaped head, restricted brain growth, or impaired cognitive development. – Nonsyndromic cases typically affect only one suture and are sporadic. – Syndromic presentations comprise 20% of cases. There are more than 180 syndromes that can cause this, including Crouzon, Pfeiffer, Apert, and Muenke syndromes. • Treatment often involves a multidisciplinary team approach with neurosurgery, craniofacial plastic surgery, oral maxillofacial surgery, ophthalmology, and genetics. Position

• Supine for metopic and coronal suture release, typically on a cerebellar head rest. • Prone for sagittal and lambdoid suture release, on a prone headholder, often with the neck extended in a modified sphinx position. Incision

Variety of different techniques • Open cranial vault remodeling (craniectomy or suturectomy) and fronto-orbital advancement • Spring-mediated cranioplasty for sagittal synostosis • Minimally invasive endoscopic reconstruction • Placement of distraction devices

Approximate Time

• Open surgery: 3–6 hours • Endoscopic surgery: 1–2 hours

EBL Expected

• Open procedures can range from 20–170% of estimated blood volume (EBV) • Endoscopic procedures can range from 1–27% of EBV (1)

Hospital Stay

• Open surgery: 3–4 days • Endoscopic surgery: 1–2 days

Special Equipment for Surgery

Special positioning equipment and padding may be needed if the prone position is anticipated. EPIDEMIOLOGY Prevalence

• Affects 3–5/10,000 live births • Syndromic cases: Chromosomal abnormalities are often noted. Mutations have been found in genes involved in the osteogenic process of the skull (most are found on fibroblast growth factor receptors [FGFRs]). • Nonsyndromic cases are sporadic, though a familial pattern has been reported as an autosomal dominant disorder. • Secondary causes include metabolic disorders (hypothyroidism), fetal teratogen exposure (phenytoin, valproic acid), and certain forms of mucopolysaccharidosis (Hurler syndrome) (2). • Deformational plagiocephaly should not be confused with true craniosynostosis. Since the advent of sudden infant death syndrome recommendations for supine sleeping positions, the incidence has increased dramatically. • Types of suture closure: – Sagittal suture (∼60%) or scaphocephaly – Unilateral (anterior plagiocephaly) or bilateral (brachycephaly) coronal suture (25%) – Metopic suture (15%) or trigonocephaly – Lambdoid suture (2–3%) or posterior plagiocephaly

Morbidity/Mortality

• Calvarium deformities • Vision problems with orbital dystocia • Increased intracranial pressure, papilledema • Neurocognitive, speech, and behavioral abnormalities

ANESTHETIC GOALS/GUIDING PRINCIPLES

Repair is recommended early in infancy (between 2 and 6 months of life) to prevent the sequelae associated with restricted brain growth and allow for normal cognitive development.

PREOPERATIVE ASSESSMENT SYMPTOMS

• There may be mild preoperative deficits in both motor and mental development. • Look for symptoms of increased intracranial pressure (visual difficulties, nausea/vomiting, somnolence, or headaches), which may present more commonly in children who are older or have fusion of multiple sutures (2).

History

• A careful history of prematurity status and course should be taken, as well as any comorbidities that may present in syndromic cases.

• Obstructive apnea can occur in some syndromic cases (Apert, Crouzon) because of abnormal airway anatomy (choanal stenosis or atresia, tracheal stenosis or abnormal tracheal cartilage). • Associated congenital disease is associated with many syndromes (Apert syndrome). • Cervical spine fusion (Apert, Crouzon, Pfeiffer), or other bone/cartilage abnormalities (syndactyly, synostosis of other joints). Signs/Physical Exam

• A good airway and facial exam is indicated in syndromic cases where a difficult airway is anticipated (small nasopharynx or fused cervical spine). Note the presence of a large tongue, shallow orbits, small mandible, and midface hypoplasia (seen in Apert and Crouzon syndromes), as this can indicate difficult mask ventilation. • Limb deformities (syndactyly) can pose challenges in venous access.

MEDICATIONS

A basic medication and allergy history should be obtained. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Baseline CBC and coagulation studies • Plain skull radiographs or ultrasonography for routine diagnosis • Brain CT scan may be helpful in syndromic or complex cases where physical examination does not provide a clear diagnosis (3). • If cervical spine fusion is a concern, cervical spine radiographs should be obtained. • Type and cross at the minimum. If an open or complicated procedure is expected, one or more units of packed red blood cells (pRBCs) should be readily available in the operating room prior to incision. CONCOMITANT ORGAN DYSFUNCTION

• If there is coexisting congenital cardiac disease, a preoperative baseline EKG and echocardiogram may be warranted to evaluate structural anatomy and function. • Renal abnormalities have been associated with syndromic presentations.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Consider oral or IV premedication in older children with anxiety, or having a parent present at induction to ease separation anxiety. • A history of difficult airway may necessitate an IV placement prior to induction; consider topical anesthetic creams to decrease pain with IV placement.

Special Concerns for Informed Consent

Potential for blood transfusion is higher in neonates and open craniectomies

Antibiotics/Common Organisms

Perioperative antibiotic prophylaxis may be indicated in cases with associated congenital heart disease. INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia with an endotracheal tube Monitors

• Standard ASA monitors • Good peripheral IV access (usually 2 large-bore IVs) (1). Consider central venous catheter placement if peripheral IV access is unsatisfactory • Consider a radial arterial line • Consider thoracic/precordial Doppler ultrasound for venous air detection • Consider a Foley catheter for longer cases

Induction/Airway Management

• IV or inhalation induction with sevoflurane • Oral or nasal endotracheal intubation with controlled ventilation. Consider a muscle relaxant to facilitate intubation. If a difficult airway is anticipated, ensure all backup equipment is at hand (LMA, fiberoptic, indirect video laryngoscopy, etc.). • Inadvertent extubation or bronchial mainstem intubation can occur during positioning, extension/flexion of the head, and movement between the supine and prone position. Securing the endotracheal tube (sometimes with silk suture or wire to alveolar ridge) and confirming the position of the endotracheal tip is extremely important. • Corneal shields can be used to protect the eyes. If the eyes are proptotic, suturing the eyes shut may be necessary.

Maintenance

• Balanced technique with volatile anesthetics, oxygen with nitrous oxide or air, IV narcotics, and a neuromuscular relaxant. Studies have shown equivalent results with isoflurane– remifentanil and sevoflurane–remifentanil techniques (2,3). • In patients with elevated intracranial pressure, care should be taken to avoid further elevations in pressure. • Typically, the incision site is infiltrated with local anesthetic (combined with epinephrine) prior to surgery. • Crystalloid should be administered for replacement of deficit and maintenance requirements. Colloids (typically albumin 5%) can be used after crystalloid replacements for decreases in BP. – Blood loss must be closely monitored and transfusions given when indicated (e.g., hemodynamic instability, hemoglobin <6 g/dL). Most of the blood loss occurs during elevation of the periosteum, with increased risk of bleeding with manipulation of the dural sinuses; after the osteotomy, there is a slow and steady blood loss. Sagittal suture craniosynostosis may increase the need for blood transfusions given the close anatomical

position to the suture (1). • A filter should be used during transfusion of all blood components. pRBCs stored <2–3 weeks should be used in young children to decrease the risk of hyperkalemia. The need for platelets, fresh frozen plasma, and cryoprecipitates is rare (in small children, ABO-matched platelets should be used. – Strategies for decreasing homologous transfusion: Directed donation, or autologous blood donation in older children Acute normovolemic hemodilution has not been shown to decrease blood transfusion requirements. Perioperative blood salvage may reduce the need for blood transfusion, but has risks of coagulopathy, hemolysis, and bacterial contamination (2). Induced hypotension is not recommended Preoperative use of recombinant human erythropoietin may reduce transfusion requirements (3). Combinations of above therapies may decrease the need for transfusions. • It is critical to closely monitor electrolytes (especially calcium and potassium) if transfusions are given. • Venous air embolism (higher incidence in open craniectomies) can occur and should be treated immediately.

Extubation/Emergence

• Plan for extubation at the end of the procedure. • Consider leaving the endotracheal tube in place if patient has a history of a difficult airway, or has experienced intraoperative instability.

FOLLOW-UP BED ACUITY

• Intensive care unit (ICU) monitoring may be indicated for neonates, longer case duration, large transfusion requirements, respiratory monitoring, and intraoperative hemodynamic instability. • For endoscopic cases, a monitored floor familiar with neurosurgical patients is adequate. • Coagulation studies and hematocrit should be followed closely. • A postoperative CT scan will often be ordered.

ANALGESIA

• IV narcotics (typically nurse or patient controlled analgesia) • IV muscle relaxants (such as Valium) are useful for muscle spasms.

COMPLICATIONS

• Infection (rare) • Blood transfusion related • Orbital or cortical injury • Dural sinus tears

• CSF leaks • Venous air embolism

PROGNOSIS

• The need for reoperation is associated with syndromic and/or multiple-suture craniosynostosis • Subsequent procedures include fronto-orbital advancement and calvarial vault reconstruction. • Postoperative helmet therapy may be used after endoscopic surgery to promote symmetric growth.

REFERENCES

1. eier PM, Goobie SM, DiNardo JA, et al. Endoscopic strip craniectomy in early infancy: The initial five years of anesthesia experience. Anesth Analg. 2011;112(2):407–414. 2. Koh JL, Gries H. Perioperative management of pediatric patients with craniosynostosis. Anesthesiol Clin. 2007;25(3):465–481, viii. 3. Chim H, Cosain AK. An evidence-based approach to craniosynostosis. Plast Reconstr Surg. 2011;127(2):910–917.

ADDITIONAL READING

• A Practical Approach to Pediatric Anesthesia, Chapter 14. Holzman RS, Mancuso TJ, Polaner DM. Lippincott Williams & Wilkins, 2008.

See Also (Topic, Algorithm, Electronic Media Element) • Venous air embolism • Blood transfusion • Autologous blood transfusion • Intracranial hypertension

CODES ICD9 756.0 Congenital anomalies of skull and face bones ICD10 Q75.0 Craniosynostosis

CLINICAL PEARLS

• Craniosynostosis is a complex condition, sometimes involving syndromes with craniofacial abnormalities and cognitive dysfunction, and often requires a multidisciplinary approach. • Syndromic cases can have a higher incidence of perioperative respiratory complications, such as obstructive sleep apnea, difficult airway, and abnormalities of the trachea.

• Early surgical intervention is standard of care. • The risk of significant blood loss, especially in neonates, requires careful preoperative planning and intraoperative vigilance. It is often prudent to begin transfusion early, before hypovolemia occurs. • The risk of venous air embolism is significant; be prepared to treat cardiovascular collapse quickly.

CRANIOTOMY FOR CEREBRAL ANEURYSM CLIPPING R. Alexander Schlichter, MD

BASICS DESCRIPTION General

• An open craniotomy is performed to clip an intact, leaking, or ruptured cerebral aneurysm that is untreatable by endovascular embolization. The first clipping was described in 1937; since then, there has been continued evolution of shape and size of clips. • A frontotemporal or pterional craniotomy is performed and the frontal and temporal lobes are gently retracted. The circle of Willis is exposed and the aneurysm is located. In most cases, the aneurysm has been imaged preoperatively by cerebral angiography to determine the location, shape, and size. • The blood supply to the aneurysm is determined/confirmed under the microscope. Doppler ultrasound may also be used to determine blood flow around the aneurysm. • Under microscopic visualization, permanent clips are placed around the neck of the aneurysm to prevent blood from entering the dome; they are MRI and biocompatible. If clipping is deemed to be inadequate, temporary clips are placed across the cerebral vessel while additional clipping and hemostasis is achieved. Temporary clips are large and easy to place and remove; they are placed proximal to the aneurysm to deprive it of blood flow and provide a bloodless field. Prolonged temporary clipping increases the risk of ischemia; thus, clipping time should be closely monitored. • To confirm the absence of a leak postclipping, one of the following surgeon- and institutiondependent techniques are performed: – Angiography. A vascular sheath is placed either preoperatively or intraoperatively (institution-dependent). – IV indocyanine green dye (IcG). Can be observed under fluoroscopy while precluding the need for IV contrast dye and placement of a vascular sheath. Strong data, however, is not available at this time to obviate angiography. – IcG and angiography. Decreases the length of angiography and exposure to IV contrast dye. Requires placement of a vascular sheath. • Advantages to craniotomy with aneurysm clipping versus endovascular embolization include definitive aneurysm ablation, lower incidence of rebleeding, decreased cost, and technical superiority in cases where the aneurysm cannot be coiled endovascularly. • Disadvantages include increased risk of bleeding, stroke, seizure, myocardial infarction, aneurysm rupture, vasospasm, and possibly recovery. Position

• Supine (prone in rare cases of occipital aneurysms) • Head pinned in a Sugita (or Mayfield) frame • Shoulder roll placed and the ipsilateral arm can be folded over the body if there is any

tension on the brachial plexus; alternatively, the arm can be tucked. • If possible, the left arm is left abducted <90° for access to IV, arterial line, and pulse oximetry. • Bed turned 90–180°

Incision

Frontotemporal or pterional incision (occipital rare). Temporalis flap, Burr hole, and then bone flap turned to expose dura. Approximate Time

• Varies depending on aneurysm size, location, and shape. Technical difficulty can arise from the aneurysm’s neck shape or blood supply. • Length can also be prolonged by intraoperative angiography.

EBL Expected

• Unruptured aneurysms: ∼500–1,000 mL. • Rupture: In excess of 2,000 mL. Sufficient blood products should be typed and crossed, in the room, and checked in the event that immediate transfusion is needed.

Hospital Stay

• Unruptured aneurysm: 8–10 days • Ruptured aneurysm: >8–10 days to manage complications.

Special Equipment for Surgery

• Sugita or Mayfield surgical frame • Surgical microscope • A variety of MRI and biocompatible temporary and permanent aneurysm clips • Angiography and accompanying radiological equipment and personnel versus fluoroscopy for IcG. • Neuromonitoring equipment and personnel

EPIDEMIOLOGY Incidence

• Cerebral aneurysms are present in 2–5% of the population. • The incidence of rupture is 1 in 10,000 patients with aneurysms.

Prevalence

• Risk of rupture increases 1–2% per year, peaking between 40 and 60 years of age. • Increased in females, smokers, polycystic kidney disease, and hypertensive patients.

Morbidity

• Rupture: 30–35% through one’s lifetime • All-cause morbidity at 1-year post-repair: 15.7% • Stroke from surgery: 1–10%.

Mortality

1-year post repair: 1.6%

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The risk of aneurysm rupture and resulting morbidity is significant during the procedure. • Adequate venous access should be established and blood products made available. • Anesthetic management revolves around managing intracranial pressure (ICP) and brain relaxation, minimizing the effects of drugs on neuromonitoring, and potentially inducing burst suppression. • Intraoperative neuromonitoring (IONM) can help detect both global and focal ischemia. • Perioperatively, tight hemodynamic management is paramount to avoid rupture, decrease bleeding in the event of rupture, or increase perfusion through collateral circulation when temporary clips are used. • Postoperative vasospasm needs to be managed aggressively with “triple H" therapy (hypervolemia, hypertension, and hemodilution) and possible endovascular intervention.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Headache or neurological changes are often incidental symptoms that lead to diagnosis • Seizures, stroke, or SAH (“worst headache of my life”). • SAH can lead to systemic changes including EKG changes, cardiomyopathy, and respiratory failure.

History

• Commonly an incidental finding on brain imaging for other complaints or trauma. • 1 in 10,000 patients with aneurysms present with subarachnoid hemorrhage (SAH). • Standard history with focus on neurologic and cardiovascular history.

Signs/Physical Exam

Full neurological exam MEDICATIONS

• Nimodipine to prevent vasospasm after SAH • Other antihypertensives • Anticonvulsants (phenytoin, levetiracetam) • Statins (associated with less vasospasm) • Steroids to treat cerebral edema • H2 Blockers, proton pumper inhibitors (PPIs) to prevent ulceration from steroid use • Stool softeners (to prevent straining)

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC, type and cross, chemistry, and coagulation panel • Head CT, MRI

• Cerebral angiogram

CONCOMITANT ORGAN DYSFUNCTION • Cerebral vascular disease • Cardiovascular disease in older patients • Polycystic kidney disease (rare)

TREATMENT PREOPERATIVE PREPARATION Premedications

Should be used sparingly; small amounts of midazolam (short duration) or opioid may be administered for preinduction line placement. Avoid other sedatives such as scopolamine, droperidol, or diazepam that may cloud the postprocedure neurological exam. Special Concerns for Informed Consent • Blood consent • Possibility of postoperative intubation

Antibiotics/Common Organisms

Gram positive coverage for skin flora with a third-generation cephalosporin INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with endotracheal tube (ETT) • Very rarely, an “awake craniotomy” (light MAC with scalp block) for aneurysms in eloquent parts of the brain Monitors

• Standard ASA monitors • Foley catheter with urometer • Arterial line (preinduciton for beat-to-beat monitoring (Cushing response, tight hemodynamic adjustments), and frequent labs (hemoglobin, electrolytes, osmolality) • Central venous access in patients with SAH, otherwise large-bore (14–18 G) peripheral access is adequate for rapid resuscitation and transfusion. • Intraoperative neuromonitoring: Usually EEG and somatosensory-evoked potential (SSEP) • Bispectral monitoring may not be possible because of pin placement or incision.

Induction/Airway Management

• Deep induction with hypnotic, opioid, and paralytic medication to avoid coughing, bucking, sharp increases in BP, and hypoxemia with laryngoscopy and intubation. • Avoid ketamine and succinylcholine as they can increase the ICP. If a RSI is warranted (e.g., SAH, risk of aspiration), the benefit of quickly securing the airway and controlling respiratory parameters outweighs the small and transient increase from succinylcholine.

• Antihypertensives and vasopressors with quick onset and short duration should be available to provide tight hemodynamic control (hypotension can cause ischemia and hypertension can cause rupture).

Maintenance

• Low-dose inhalational agents, opioids (bolus or infusion), and muscle relaxation can be used versus total IV anesthesia with propofol (may have better effects on ICP, brain relaxation, and IONM). Nitrous oxide is generally avoided. • CO2. The ETCO2 is typically maintained between 25 and 30 mm Hg. If concerned about dead space (chronic obstructive pulmonary disease, COPD, pneumonectomy) follow PaCO2.

Hypercarbia can lead to increased cerebral blood flow (CBF) and increased ICP. Rapid drops in CO2 can increase the transmural pressure of the aneurysm and cause rupture. Severe

hypocarbia (<25 mm Hg) can cause ischemia. • Anticonvulsants should be loaded during the case. • Corticosteroids (dexamethasone) are given to treat cerebral edema and help prevent PONV. • ICP. Diuresis with mannitol and the possible addition of a loop diuretic to decrease brain water and volume. Maintain euvolemia by replacing urine output. • Fluids. Normal saline is preferred due to its high osmolality; however, it can cause a metabolic hyperchloremic acidosis. • IONM. Communicate anesthetic technique and changes to neuromonitoring to avoid masking or misconstruing changes from the surgical field. • Tight hemodynamic control. Be prepared to increase BP (with fluids and pressors versus inotropes) during temporary clipping or occlusion of the internal carotid artery to improve collateral flow. Be prepared to return BP to normal after clipping. Avoid hypotension to decrease risk of ischemia. • Burst suppression with thiopental or propofol may be used during temporary aneurysm clipping. • Temperature. Mild intraoperative hypothermia (to 33°C) is controversial. Data has not proven any benefit in healthy patients with unruptured aneurysms. Extubation/Emergence

• For uncomplicated cases, extubation followed by a neurological exam is important to identify possible surgical complications. In patients who require postoperative intubation, a neurological exam should be attempted before reanesthetizing and transporting to the intensive care unit (ICU). The inability to perform or an abnormality in the neurological exam requires immediate neuroimaging before transport to the ICU. • Avoid bucking, coughing, or hypertension • Patients should remain flat (or reverse Trendelenburg) if an angiography sheath was placed.

POSTOPERATIVE CARE BED ACUITY

Direct transport to the ICU, preferably a neuro ICU with full monitoring. ANALGESIA

• Analgesia should be targeted to treat pain while minimizing sedation; utilize low-dose IV or oral opioids. • Rectal or IV acetaminophen • Avoid NSAIDs (postoperative bleeding)

COMPLICATIONS

• Aneurysmal rebleeding: Tight BP control can help prevent rebleeding. • Stroke and seizure • Vasospasm should be aggressively treated with “Triple H” therapy (hypertension, hemodilution, hypervolemia).

PROGNOSIS

In unruptured aneurysm, the prognosis is good. SAH has a much poorer prognosis, especially if vasospasm occurs.

REFERENCES

1. Molyneux A, Kerr R, Stratton I. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: A randomised comparison of effects of survival, dependency, seizures, rebleeding, subgroups. Lancet. 2005;366(9488):809–817. 2. lshekhlee A, Mehta S, Edgell RC, et al. Hospital mortality and complications of electively clipped or coiled unruptured intracranial aneurysms. Stroke. 2010;41:1471–1476. 3. Zipfel GJ, Dacey RG. Update on management of unruptured intracranial aneurysms. Nuerosurg Focus. 2004;17. 4. Todd MM, Hindman BJ, Clarke WR, et al. Mild intraoperative hypothermia during surgery for intracranial aneurysm. N Engl J Med. 2005;352(2):135–145. See Also (Topic, Algorithm, Electronic Media Element) • Cerebral aneurysm and endovascular embolization • Subarachnoid hemorrhage • Transcranial Doppler • Intracranial hypertension • Electromyelogram • Burst suppression

CODES ICD9 437.3 Cerebral aneurysm, nonruptured ICD10 I67.1 Cerebral aneurysm, nonruptured

CLINICAL PEARLS

• Although open aneurysm clipping is associated with a higher morbidity than the endovascular approach, endovascular embolization may not be technically possible. • The risk of rupture is significant and ICP and BP must be controlled before clipping. • IONM can help detect subclinical focal and global ischemia.

CRANIOTOMY FOR INTRACRANIAL HEMORRHAGE Carsten Nadjat-Haiem, MD Keren Ziv, MD

BASICS DESCRIPTION General

• Causes of intracranial hemorrhage include cerebrovascular aneurysm or arteriovenous malformation (AVM) rupture, malignant hypertension, trauma, anticoagulation therapy, and tumors. • Intracranial hemorrhage carries a high-risk for morbidity and mortality; therefore, prompt diagnosis and medical and/or surgical management are cornerstones of therapy. • Medical management is usually performed for small hemorrhages with minimal deficits, as clot can be absorbed by the body. It is also performed before and after surgical aneurysm clipping to gain the best outcome and includes seizure prophylaxis and therapy, management of intracranial pressure, and prevention of vasospasm. However, despite ongoing research, major advancements and improvements have not been made in recent years. • Surgical management may be performed for aneurysm clipping as the risk of re-bleed can reach up to 35% within 14 days of the initial bleed (focus of this chapter), AVMs, or large hemorrhages near the surface of the brain that are accompanied by neurologic deterioration, brainstem compression, or hydrocephalus. Position

• Determined by the site of aneurysm (80% occur in the anterior circulation), AVM, or hematoma, surgeon preference, and patient factors such as intracranial pressure (ICP). Possibilities include supine, semilateral, lateral, prone, and sitting; variations of these positions can also be employed. • Some degree of head elevation is usually employed to aid in venous drainage and brain relaxation. Air embolism remains a risk, even when head elevation is minimal. • The sitting position must be chosen very carefully, and is typically only for patients where either brain relaxation cannot be achieved because of very high ICP, or due to the surgical access site. The risk of clinically significant venous air embolism is high and steps should be taken to reduce the risk and ensure early detection (volume loading, precordial Doppler, and central venous catheter placement at the superior vena cava-right atrium junction to aspirate air). • These procedures tend to be long, and therefore, it is imperative to pay very close attention to proper positioning, heavy padding, and securing of the patient. Incision

Depends on the location of the lesion and surgeon preference.

Approximate Time

Very variable, from 90 minutes to 16 hours EBL Expected

• Typically on the order of a few hundred milliliters for aneurysms that do not rupture. • If the aneurysm ruptures, blood loss will be brisk, and if the aneurysm is not rapidly clipped, patients can exsanguinate. • It is advisable to have at least two units of packed red blood cells immediately, and further blood products and volume expanders easily available.

Special Equipment for Surgery

Operating microscope, possibly 3D navigational equipment, and electrophysiological monitoring equipment. EPIDEMIOLOGY Incidence

• Subarachnoid hemorrhage (SAH): 9 out of 100,000 people annually. By cause: – Ruptured aneurysms: 85% – AVMs: 10% – Cerebral hemorrhage: 10% – Others (tumors) • Risk increases with age

Prevalence

About 1–2% of the population has at least one cerebral aneurysm. Morbidity

• If the early course after aneurysm rupture is survived, 25% of patients will have significant restrictions in their lifestyle, and only 20% will have no residual symptoms. • Other problems include long-term cognitive impairment, depression, fatigue, headache, posttraumatic stress disorder (PTSD), and hypopituitarism.

Mortality

Overall, survival is poor with the death rate after SAH approaching 50%. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Prevention of rebleeding during induction of anesthesia and other stimulating parts of the procedure. • Prevention of vasospasm (triple H therapy: Hypertension, hemodilution, hypervolemia) • Management of increased ICP. • Brain “relaxation”

PREOPERATIVE ASSESSMENT SYMPTOMS

• Increased ICP can present as headache, nausea and vomiting, seizures, or altered sensorium. • Focal neurologic findings associated with hemorrhage.

History

Most intracranial aneurysms are asymptomatic and remain undetected until the time of rupture. Signs/Physical Exam

A thorough neurologic exam needs to be performed to assess the baseline status of the patient so that it can be compared to the postprocedure exam. In this fashion, subtle changes can be picked up, and further diagnostics and therapeutics can be pursued in a timely fashion. MEDICATIONS

• Mannitol • Furosemide • 3% saline • Vasoactive substances such as calcium channel blockers to prevent vasospasm and others to control BP. • Steroids for cerebral edema

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC to assess hemodilution during triple H therapy. • Chem 7 to assess for cerebral salt wasting (hyponatremia and hypokalemia) due to release of brain and atrial natriuretic hormone or syndrome of inappropriate antidiuretic hormone secretion (SIADH). • EKG: SAH often leads to changes that are consistent with acute ischemia (QT prolongation, Q waves, cardiac dysrhythmias). • Echocardiogram only needs to be obtained if cardiac ischemia or failure is suspected. • Chest radiograph is usually not indicated unless there is a suspicion of neurogenic pulmonary edema. • Imaging modalities include CT angiogram, angiogram, MRI/MRA

CONCOMITANT ORGAN DYSFUNCTION

• Cardiac rhythm disturbances will occur in up to 90% of patients with SAH. • Ischemic cardiomyopathy may develop in a small percentage of patients due to vasospasm and high catecholamine state. This needs to be treated in a manner similar to ischemia from coronary artery disease secondary to atherosclerosis. This ischemia is usually reversible if treated properly, and patients recover well. • Neurogenic pulmonary edema (NPE) may develop within minutes to hours after injury. It manifests as a marked increase in pulmonary interstitial and alveolar fluid, with resultant dyspnea, tachypnea, tachycardia, basilar rales, copious frothy sputum, possible hemoptysis, and hypoxemia.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Patients with altered sensorium or with increased ICP should be cautiously, if at all, premedicated; small changes in CO2 tension can lead to large changes in ICP and obtundation.

Special Concerns for Informed Consent

Potential for prolonged intubation and pharmacologic induced coma. Antibiotics/Common Organisms

Cefazolin for skin organisms q4h prophylactically. INTRAOPERATIVE CARE Choice of Anesthesia

General endotracheal anesthesia Monitors

• Standard ASA monitors • Foley catheter • Arterial line allows for tight BP monitoring and aids in resuscitation should the aneurysm or AVM re-rupture. • Central line should be strongly considered given the risk for a venous air embolism, massive blood loss, and the possible need for vasoactive and barbiturate administration. • EEG monitoring and evoked potentials are not the standard of care, but should be strongly considered in cases of giant and wide neck aneurysms, aneurysm in close proximity to other vessels, high ICP, large SAH, or in those who are otherwise at risk for cerebral ischemia. No trial has shown an outcome benefit. Findings may be used to further direct therapy and intervention. Induction/Airway Management

• There is no single recommended induction choice. Goals are as follows: – Keep the aneurysm’s transmural pressure gradient stable. – Maintain adequate cerebral perfusion and oxygenation. – Avoid rapid changes in ICP. • The risk of aneurysm rupture with induction is about 1% (data on re-rupture is not available). Good choices for induction are propofol, IV lidocaine, esmolol, and short-acting opioids such as remifentanil, but other agents may be used with equal efficaciousness. • Usually, intermediate-acting nondepolarizing muscle relaxants are used. Succinylcholine will raise the ICP transiently, but to a lesser degree than an unsmooth induction. Maintenance

• Positioning and head pinning are stimulating events, and may need further doses of

induction agents. Scalp infiltration with local anesthetics is useful in attenuating the stress response. Long-acting agents are avoided due to the risk of hypotension. • Brain relaxation. Reducing the content of the cranial vault for surgical exposure is paramount. – Mannitol 0.5–1 mg/kg over a period of about 20–30 minutes. Administration may cause severe hypotension, especially in hypovolemic patients. – Furosemide – Cerebrospinal fluid drainage – Head elevation – Avoidance of venous outflow obstruction by limiting head rotation (aids in brain relaxation) – If brain relaxation is inadequate, switching from volatile agents (usually kept below one MAC) to a propofol infusion will improve relaxation significantly. • BP is kept close to normal during the case. However, if the surgeon applies temporary clips or the aneurysm is secured, BP is elevated to improve collateral flow. • Cerebral protection. At this time, no cerebral protection study has shown a decrease in the risk of ischemia. – Mild hypothermia will reduce cerebral metabolic rate of oxygen (CMRO2), but will not

affect morbidity or mortality. It will, however, aid in brain relaxation, and if the temperature does not fall below 34.5°C, it has no negative effect on infection rate, bleeding, and wound healing. – Barbiturate administration titrated to burst suppression is used in some centers to protect the brain from ischemia and provide brain relaxation. Again, no outcome evidence exists to support this practice.

Extubation/Emergence

• Nausea should be preempted with multimodal therapy. • Extubation should be smooth. Postoperative intubation may be considered in patients with high-grade hemorrhage or if there is any doubt about their ability to protect their airway. • Hypertension in the early postoperative period is common. Mild hypertension (20%) should be left untreated as it will aid in collateral flow and is part of the “triple H" therapy to avoid vasospasm. Hypertension beyond this range will need to be treated with calcium channel or beta blockers. • Pain medications should be given cautiously to avoid clouding of the sensorium, and respiratory depression. • Early neurological exam is paramount as to guide whether CT scanning, angiography, or initiation of “triple H" therapy is warranted.

POSTOPERATIVE CARE BED ACUITY

All patients will need to be admitted to the ICU for frequent neurological assessment and tight BP control. ANALGESIA

Surgical pain is usually easily managed with small doses of long-acting opioids. Their use can be obviated by a field block with long-acting local anesthetic intraoperatively. COMPLICATIONS

• Postoperative hemorrhage • Vasospasm • Hydrocephalus

PROGNOSIS

Highly variable, and directly correlated to hemorrhage grade.

REFERENCES

1. Gelb AW. Anesthesia and subarachnoid hemorrhage. Revista Mexicana de Anesthesiologia. 2009;32(1):S168–S171. 2. Coghlan L, Hindman B, Bayman E, et al. Independent associations between electrocardiographic abnormalities and outcomes in patients with subarachnoid hemorrhage: Findings from the Intraoperative Hypothermia Aneurysm Trial. Stroke. 2009;40:412–418. 3. Molyneux A, Kerr R, Stratton I, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: A randomised trial. Lancet. 2005;366: 809–817.

ADDITIONAL READING

• Pasternak JJ, Lanier WL. Neuroanesthesiology update. J Neurosurg Anesthesiol. 2009;21:73–97.

See Also (Topic, Algorithm, Electronic Media Element) • Cerebral embolization • Intracranial hypertension • Venous air embolism • Electroencephalogram (EEG)

CODES ICD9 432.9 Unspecified intracranial hemorrhage ICD10 I62.9 Nontraumatic intracranial hemorrhage, unspecified

CLINICAL PEARLS

• Good brain relaxation is of paramount importance.

• Be prepared to administer blood, lower the blood pressure, and administer barbiturates should the aneurysm re-rupture. • Postoperative care (i.e., institution of “triple H" therapy, avoidance of nausea, and BP control) are important to good outcomes.

CREATININE CLEARANCE Julie McSwain, MD, MPH Sylvia H. Wilson, MD

BASICS DESCRIPTION

• Creatinine clearance (CrCl) measures the rate at which the kidneys remove creatinine from the blood. It is expressed as volume of blood plasma that is cleared per unit of time (milliliters per minute). • CrCl functions to estimate the glomerular filtration rate (GFR). Thus, it can serve as a tool to diagnose renal dysfunction or evaluate the progression of renal disease. • CrCl is traditionally measured by a 24-hour urine collection (2-hour collections may also be performed) • Normal values (may vary by laboratory): – Men: 120 mL/min (range 97–137) – Women: 95 mL/min (range 88–128) – Parturients: 150–200 mL/min PHYSIOLOGY PRINCIPLES

• Creatinine is a by-product of creatine phosphate metabolism in skeletal muscle and of dietary meat. Creatinine is: – Released into the circulation at a constant rate – Freely filtered by the glomerulus – Not metabolized or absorbed by the kidney – Not affected by a normal diet or normal physical activity – Secreted into the proximal tubule of the nephron; 10–15% – Reduced with age due to declining muscle mass. • CrCl provides the clinician with a method to estimate the GFR. – GFR is accepted as the most accurate measure of renal function. However, it is costly and cannot be performed with routine laboratory monitoring (requires IV or subcutaneous administration of a marker with repeat collections of urine samples every 30–45 minutes). – Traditional CrCl requires a 24-hour urine collection as well as a serum creatinine blood draw in order to calculate the value (Cockroft and Gault equation). CrCl should be adjusted for patient size and incorporate body surface area when comparing to normal values (1)[B]. – A small amount of creatinine is secreted by the proximal renal tubule; hence, CrCl measurements overestimate true GFR by 10–15%. – If the secreted fraction is ignored, then all of the filtered creatinine would be excreted in the urine. Calculation is as follows: GFR * SCr = UCr * V; where SCr = serum creatinine clearance, UCr = urine creatinine concentration, V = urine volume. Note, however, that

this makes the assumption that there is no secretion out of the renal tubule. – Cimetidine administration is a technique that is utilized to eliminate creatinine secretion by the proximal tubule and provide a more accurate estimation of GFR (2)[B]. • Age – Creatinine excretion steadily declines by 50% between ages 50 and 90 years due to decreasing skeletal muscle mass even if renal disease does not exist (3)[B]. – CrCl decreases ∼6.5 mL/min for every 10 years past the age of 20 years. • Artificially increased CrCl is seen with: – Strenuous exercise, trauma/burns, excessive protein intake (especially beef), carbon monoxide poisoning, hypothyroidism, and pregnancy. • Errors in CrCl – Calculation errors can result from incomplete or variable urine collections. This may be reduced by having the patient empty the bladder and discard urine at the start of the test. Incomplete collections typically underestimate CrCl and thus GFR. – Most formulas for CrCl assume a steady state. Thus, increasing creatinine levels during the collection period can also result in errors. • A 2-hour urine collection may be used to readily estimate CrCl if urine flow is induced by diuresis (4)[B]. – May be more feasible to perform in certain patient populations (e.g., critically ill patients) and allows for serial calculations over time to track changes in GFR. – These collections should be performed at the same time of day to avoid diurnal variation.

ANATOMY

• The kidneys function in volume control, pH and electrolyte balance, hormone secretion, and excretion of waste products and toxins. • They are located in the paravertebral gutters behind the peritoneum at the level of the lower thoracic vertebrae. Renal arteries originate from the aorta at the level of the first lumbar vertebra and provide blood to the kidneys. • The kidney is surrounded by a fibrous capsule and composed of an outer cortex and an inner medulla. • The nephron is the functional unit of the kidney; there are ∼1 million nephrons per kidney. It serves as the site where urine is concentrated and transmitted to the ureters. Additionally, it clears the plasma of metabolic breakdown products including creatinine and urea. • Nephrons comprise a filtering component with an enclosed capillary network (glomerulus) that is attached to a complex tubule system where urine is modified (proximal collecting tubule, loop of Henle, distal collecting tubule). Urine from the tubules drain into the collecting duct and finally into the ureters. Nephrons are classified into two types based on if they have a long or short loop of Henle.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Renal impairment can be seen with renal hypoperfusion, renal outflow obstruction (usually both kidneys), cancer, shock, life-threatening infections, heart failure, dehydration, acute or chronic renal failure, end-stage renal disease, cirrhosis, and diuretics. • Serum creatinine levels can be readily measured as part of a basic metabolic panel. However, the value does not linearly increase as GFR decreases.

• Renal disease typically exists along a spectrum from decreased renal reserve to renal failure. Additionally, physical manifestations of renal disease do not typically appear until a large percent of nephrons are damaged – GFR usually must fall below 25 mL/min before clinical signs and symptoms appear. – A minimum CrCl of 10 mL/min is required to sustain life without the aid of dialysis. • CrCl may become a less accurate predictor of GFR as kidney function declines. – The body increases the amount of creatinine that is secreted to compensate for increased serum creatinine. This leads to an overestimation of true GFR. – Moderate-to-severe renal disease: Renal function may be better estimated by averaging the CrCl with the urea clearance (Curea). In this patient population, CrCl typically overestimates the GFR due to creatinine secretion and Curea typically underestimates the

GFR due to urea reabsorption in the nephron. – Severe renal disease: Bacterial creatininase activity often increases resulting in augmented CrCl outside the kidney. This results in less filtered serum creatinine and leads to an overestimation of CrCl.

PERIOPERATIVE RELEVANCE

• Perioperatively, there are several stressors that can affect renal function, particularly in patients with preexisting disease (hypoxia, hypovolemia, hypotension, nephrotoxic drugs). Thus, the anesthesia provider should be aware of the extent of renal disease as well as any therapies the patient may be taking such as antihypertensive agents, electrolyte replacements, erythropoietin, immunosuppressants (if post-transplant), and dialysis • Unfortunately, 24-hour CrCl calculations are often impractical in the perioperative setting. Although they provide a good estimate of GFR, they are time consuming and labor intensive. – In lieu, serum creatinine measurements are often utilized, although they have little predictive value of the GFR. – Preexisting renal disease thus poses a conundrum. In renal disease, the anesthesia provider lacks sensitive, specific, and low-cost tools to preoperatively assess and risk stratify patients at risk for perioperative renal complications. – Nonetheless, the anesthesia provider has the capability to either preserve or deteriorate baseline renal function. • Volume status should be preoperatively assessed in patients with renal disease. Patients that are volume depleted (e.g., recent dialysis) may demonstrate an exaggerated response to IV induction agents. • Concomitant disturbances include electrolyte dysfunction (acidosis, hyperkalemia), insulin resistance, anemia, uremia, abnormal coagulation, and cardiac dysfunction. • Medication adjustments – Succinylcholine. Patients with chronic renal disease do not exhibit an exaggerated hyperkalemic response; however, if they have an elevated baseline potassium levels, there is a potential for hyperkalemic-induced arrhythmias. – Cisatracurium and atracurium are metabolized by Hoffman degradation and do not depend on renal clearance for metabolism. – Antibiotics often require dose reduction when the CrCl falls below 50 mL/min.

– Volatile agents. Sevoflurane has a theoretical risk of producing the nephrotoxic Compound A (not been supported in clinical practice). Desflurane and Isoflurane have not been shown to worsen renal dysfunction in patients with preexisting disease (5)[A]. • Postoperative CrCl may be a useful predictor of early acute renal failure (ARF); particularly in trauma patients (6)[B]. ARF carries a high morbidity and mortality rate. • Underestimation of CrCl may occur with the following medications: – Barbiturates and cephalosporins may falsely increase serum creatinine. – H2 blockers and salicylates can decrease tubular secretion of creatinine.

EQUATIONS

• Creatinine clearance (CCr) – GFR = [UCr × V]/SCr

Derived from GFR × SCr = UCr × V; where GFR is glomerular filtration rate, SCr is

serum creatinine concentration, UCr is urine creatinine concentration, and V is urine

volume. – GFR = [CCr + Curea]/2

For patients with moderate-to-severe renal disease – CCr = (140 – age) × IBW/(SCr × 72)▒ CCr is multiplied by 0.85 for females

Cockcroft and Gault equation IBW = Ideal Body Weight • [CCr × 1.73]/BSA

– Corrected CrCl adjusted for standard BSA

REFERENCES

1. Pai MP. Estimating the glomerular filtration rate in obese adult patients for drug dosing. Adv Chronic Kidney Dis. 2010;17:e53–e62. 2. Kabat-Koperska J, Safranow K, Golembiewska E, et al. Creatinine clearance after cimetidine administration: Is it useful in the monitoring of the function of the transplanted kidney. Ren Fail. 2007;29:667–672.

3. Fliser D. Assessment of renal function in elderly patients. Curr Opin Nephrol Hypertens. 2008;17:604–608. 4. Sladen RN, Endo E, Harrison T. Two hour vs. twenty-two hour creatinine clearance in critically ill patients. Anesthesiology. 1987;67:1013–1016. 5. Litz RJ, Hubler M, Lorenz W, et al. Renal responses to desflurane and isoflurane in patients with renal insufficiency. Anesthesiology. 2002;97:1133–1136. 6. Shin B, Mackenzie C, Helrich M. Creatinine clearance for early detection of posttraumatic renal dysfunction. Anesthesiology. 1986;64:605–609.

ADDITIONAL READING

• Bazari H. Approach to the patient with renal disease. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 115.

CLINICAL PEARLS

• Following GFR trends can help estimate the progression of renal disease as well as the effectiveness of treatment, however it is costly and cumbersome. CrCl is a surrogate for estimating GFR and serial CrCl measurements are a sensitive method for following renal dysfunction. However, a 24-hour CrCl may also be impractical in the perioperative setting and a 2-hour CrCl may be performed in certain patients. • CrCl may slightly overestimate GFR in patients with normal kidneys (10–15%) and severely overestimate GFR in patients with declining kidney function due to increased Cr secretion into the nephron. • Medications that alter CrCl levels include some cephalosporin antibiotics, aminoglycosides, amphotericin B, cimetidine, captopril, quinine, quinidine, procainamide, phenytoin, vitamin C, and trimethoprim.

CRICOTHYROIDOTOMY Jennifer Wu, MD, MBA

BASICS DESCRIPTION

• Cricothyroidotomy is a surgical airway through the cricothyroid membrane (below the vocal cords) that allows ventilation of the trachea and bypasses the oropharynx and upper airway. • The airway can be obtained quickly in emergencies and “cannot intubate, cannot ventilate” situations. It can be performed by a surgeon, anaesthetist, intensivist, or emergency physician. • Techniques: – Surgical – Seldinger – Needle (cannula) PHYSIOLOGY PRINCIPLES

• Indications – Cannot intubate, cannot ventilate – Airway obstruction: Foreign body, angioedema – Massive facial or nasal trauma – Cervical spine instability causing an inability to adequately ventilate – Fractured larynx (often from a hanging injury) – Chemical inhalation injury • Contraindications – Inability to indentify landmarks – Underlying abnormality, such as a tumor – Tracheal transection – Due to risk of subglottic stenosis, a needle cricothyroidotomy is preferred in pediatric patients. • Advantages of cricothyroidotomy over tracheotomy – Cricothyroid membrane is more superficial and easier to access than tracheal rings – Cartilage incision is not necessary – Less vascular – Can be performed more rapidly; experienced personnel can perform the procedure within 30 seconds • Disadvantage – Not a permanent airway and must be converted to a tracheotomy within 24 hours in the operating room due to the risk of developing subglottic stenosis ANATOMY

The cricothyroid membrane lies between the thyroid cartilage superiorly and the cricoid

cartilage inferiorly. Identify the thyroid cartilage with the thumb and index finger and then move the fingers caudally until a space is felt between the thyroid and cricoid cartilages.

FIGURE 1. Anatomy of the cricothyroid membrane.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Failure to secure a surgical airway in an emergency or “cannot intubate, cannot ventilate” situation is most likely due to operator inexperience or a delay in the decision to obtain a surgical airway. – The use of training with cadavers improves operator confidence (2). – The use of simulator training shows improvement in operator skills and placement time after practicing five times (3). – The number of practice procedures appears to be more important in determining success than the technique chosen – However, one study found that the Seldinger technique resulted in a significantly shorter time to first ventilation and fewer injuries than with the surgical technique (4). • Immediate complications include the following: – Bleeding; although less likely than with tracheostomy placement, it can be significant if a large neck vein is lacerated. – Insertion into subcutaneous tissue – Scalpel injury to the posterior trachea and injury to the esophagus – Injury to the thyroid, vocal cords, and vessels in the event of wrong landmarks • Jet ventilation via a needle or cannula cricothyroidotomy has the risk of barotrauma, pneumothorax, subcutaneous emphysema, and hypercarbia.

PERIOPERATIVE RELEVANCE

• Although emergency airway situations and “cannot intubate, cannot ventilate” situations can arise at anytime, the majority occur during the induction of anesthesia. • The anesthesia practitioner must have the ability to quickly recognize when an airway

becomes difficult and formulate a plan for securing a method of ventilation. • When a “cannot intubate, cannot ventilate” situation arises, the American Society of Anesthesiologists (ASA) Difficult Airway Algorithm should be followed. Upon failure of an laryngeal mask airway (LMA) or alternative noninvasive technique to secure the airway, a surgical cricothyroidotomy should be performed (1). Poor outcome is related to length of time taken to make the decision to convert to surgical airway and time taken to perform the technique. • All techniques include the following: – Positioning the patient with hyperextension of the head, if possible – A shoulder roll, if possible – Palpation of the cricoid and thyroid cartilages. – Prep of the neck with Betadine, if possible – Local anesthetic if the patient is conscious • Surgical technique: Use a number 20 scalpel to make a horizontal or vertical incision through the skin followed by a horizontal incision through the cricoid membrane. Place a tracheal hook at the incision site, and apply caudal and outward traction to the cricoid cartilage. Remove the blade. Place a cuffed tracheal tube or tracheostomy tube and inflate. Confirm ventilation with end-tidal CO2 (ETCO2) and bilateral breath sounds.

FIGURE 2. Surgical cricothyroidotomy. An incision with a scalpel is made in the skin, followed by a horizontal incision through the cricothyroid membrane. An endotracheal tube or tracheostomy is inserted.

• Seldinger technique (various kits are available): Stabilize the thyroid cartilage and make a vertical incision in the skin over the cricothyroid membrane. Insert the 19 g catheter with a 5 cc syringe attached and aspirate for air to confirm entry into the trachea. Secure the catheter with the non-dominant hand and remove the syringe and needle. Advance the guidewire through the catheter and then remove the catheter. Feed the dilator and airway catheter over the wire. Remove the dilator and wire simultaneously. Connect the airway catheter to an AMBU bag or ventilator and confirm ETCO2 and bilateral breath sounds.

FIGURE 3. Seldinger technique and needle cricothyroidotomy utilize a needle attached to a syringe to identify and access the airway. The catheter is left in place and the needle and syringe are removed.

FIGURE 4. Seldinger technique. Once the airway has been accessed (as in Figure 3), a guidewire is threaded through the catheter and the catheter is removed. The dilator with the airway catheter is then inserted over the guidewire and the guidewire and dilator are removed at the same time.

• Needle (cannula) cricothyroidotomy technique: Performed by placing a needle with a catheter (such as a large-bore IV) through the cricothyroid membrane. Using a syringe attached to the needle, aspirate air to confirm that the trachea has been entered. Leave the catheter in place and remove the needle. To ventilate via the catheter, attach a jet nozzle and use jet ventilation. When initiating jet ventilation, the starting pressure should be set at 25 psi and increased as needed. The maximum pressure should not exceed 50 psi, if possible, to provide acceptable ventilation. If jet ventilation is unavailable, remove the plunger from a 3-mL syringe; attach the syringe to the catheter. Insert the connector of a size 7.0 endotracheal tube into the syringe, then connect an bag or ventilator. This airway should be converted to a tracheostomy within 45 minutes, as the risk of hypercarbia is significant.

REFERENCES

1. ombes X, Jabre P, Amathieu R, et al. Cricothyrotomy in emergency context: Assessment of a cannot intubate cannot ventilate scenario. Ann Fr Anesth Reanim. 2011;30(2):113–116.

[Epub 2011 Feb 1.] 2. atif R, Chhabra N, Ziegler C, et al. Teaching the surgical airway using fresh cadavers and confirming placement nonsurgically. J Clin Anesth. 2010;22(8):598–602. 3. Wong DT, Prabhu AJ, Coloma M, et al. What is the minimum training required for successful cricothyroidotomy? A study in mannequins. Anesthesiology. 2003;98(2):349–353. 4. Schaumann N. Evaluation of Seldinger technique emergency criocothyroidomy versus standard surgical cricothyroidomy in 200 cadavers. Anesthesiology. 2005;102(1):7–11.

ADDITIONAL READING

• Caplan RA, Benumof JL, Berry FA, et al. Practice guidelines for management of the difficult airway. An updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology. 2003;98:1269–1277. See Also (Topic, Algorithm, Electronic Media Element)

• Tracheostomy • Difficult airway • Jet ventilation

CLINICAL PEARLS

• Cricothyroidotomy is an invasive technique used to secure the airway when other methods of ventilation have failed. • Successful outcome is related to the time taken to make the decision to perform a surgical airway and the skill of the provider in performing the procedure.

CROHN’S DISEASE Andrea Parsons, MD

BASICS DESCRIPTION

• Inflammatory bowel disease that shows inflammation of any portion of the GI tract from the mouth to the terminal ileum with rectal sparing. The disease is characterized by slowly progressive spread with alternating periods of remission and exacerbation. • Patients present for surgical management of problems related to the disease, such as intestinal obstruction, perirectal abscesses, bleeding, fistulas, perforation, toxic megacolon, strictures, and cancers, or for management of nonrelated problems. EPIDEMIOLOGY Incidence

• US: 3–14 cases per 100,000 persons (1) • Bimodal distribution with diagnosis peaking in the teens and 20s and then in the 50–70s (1)

Prevalence

• US: 26–200 per 100,000 persons (2) • Females have a slightly higher prevalence (2) • More frequent in people who have a first-order relative with the disease (2).

Morbidity

• There is no cure for Crohn’s disease and patients suffer from flare-ups that can cause significant discomfort and weight loss. • If medical therapy is not effective, surgical resection of inflamed bowel is the treatment of choice.

Mortality

Mortality rate is low, but there is an increased rate of small bowel and colorectal cancers. ETIOLOGY/RISK FACTORS

• The exact cause is unknown. There is some evidence to suggest that normal intestinal flora can trigger an aggressive and inappropriate immune reaction in patients with a multifactorial genetic predisposition. However, no specific environment, dietary, or infectious causes have been identified (3). • Carries a genetic predisposition as evidenced by a higher prevalence in familial and twin studies (3).

PATHOPHYSIOLOGY

• Inflammatory responses result in patchy, cobblestone, transmural inflammation of the GI

tract between the mouth and anus. Conversely, ulcerative colitis is continuous, mucosal inflammation, mostly in the lower intestine and rectum. – Cytokines lead to differentiation of lymphocytes to T cells (mainly helper T cells type 1), leading to immune system activation, inflammatory response, and subsequent damage of the intestinal mucosa – Macrophages cause granuloma formation – Cytokine release includes interleukin-1 (IL-1) which causes diarrhea and acts as a pyrogen. Other cytokines released include IL-6, IL-8, and tumor necrosis factor-α (TNF-α). • Electrolyte abnormalities and malnutrition occur secondary to diarrhea and pain. • Anemia occurs due to blood loss (acute or chronic) and due to malabsorption of iron, vitamin B12, and folate. • Secondary peritonitis results from abscess formation that can manifest with abdominal pain. It can be acute or slow to develop, often dull, and poorly localized initially. This can progress to severe pain and is treated with antibiotics. • Diagnosis can be made with a biopsy of affected tissue via endoscopy. Imaging with small bowel follow-through, CT scan, and MRI can aid in diagnosis.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess the severity of disease, recent exacerbations, intravascular fluid status, and electrolyte abnormalities, as well as treatment and medication history. • Anesthetic plan should focus on fluid and electrolyte management, assessment of anemia, and use of steroids.

PREOPERATIVE ASSESSMENT SYMPTOMS

Exacerbations consist of diarrhea (increased frequency, fluidity, daily volume of stool), abdominal bloating, distention, discomfort, cramps particularly after meals, acute pain in the lower right abdomen, hyperactive bowel sounds, infection, blood in stool (or greasy, foulsmelling, fatty stool), nausea and vomiting, weight loss, dry mouth. History

• Acute flare versus chronic condition • History of anti-inflammatory, antidiarrheal, and antidepressant use • Severity, especially with regard to fluid and electrolyte status • Current hyperalimentation therapy • Diabetes and hypertension from chronic steroid use

Signs/Physical Exam

• Signs of dehydration—decreased skin turgor, decreased capillary refill, decreased urinary output, tachycardia, hypotension, etc. • Signs of electrolyte abnormalities—ECG changes, muscle weakness, etc. • Rectocutaneous fistulas • Malnutrition and vitamin deficiencies • Painful lower extremity swelling may indicate deep venous thrombosis (increased risk);

shortness of breath or hypoxia should warrant consideration of a pulmonary embolism.

TREATMENT HISTORY

Surgical resection of affected portions of the intestines MEDICATIONS

• Maintenance therapy typically includes 5-aminosalicylic acid, steroids, and immunomodulators for refractory disease (azathioprine, methotrexate, infliximab) (4). • Exacerbations are commonly treated with 5-aminosalicylic acid, glucocorticoids, and antibiotics (4)

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC to assess for anemia and hemoconcentration • Complete metabolic panel (BUN/Cr ratio of 20:1 may indicate dehydration; low bicarbonate values may indicate acidosis due to dehydration or infection) • Coagulation studies if liver disease is present • EKG may be considered for electrolyte abnormalities or patient specific indications • Type and screen or type and cross.

CONCOMITANT ORGAN DYSFUNCTION

Extraintestinal manifestations include: • Oral lesions: Aphthous stomatitis, canker sores found between the gums and lower lip or along the sides or base of the tongue. • Arthritis, including ankylosing spondylitis, can result in reduced flexibility and mobility as well as joint pain. Metabolic bone disease may also be present. • Skin disorders range from erythema nodosum (tender, red nodules that appear over the shins and ankles as well as the arms) to pyoderma gangrenosum to perianal lesions (enterocutaneous fistulas, abscesses, anal fissures). • Eye disorders: Episcleritis, uveitis, and dry eyes • Renal complications include kidney stones and hydronephrosis • Liver: Jaundice, fluid retention, and primary sclerosing cholangitis CIRCUMSTANCES TO DELAY/ CONDITIONS

• Significant hypovolemia and/or electrolyte disturbances • Severe anemia requiring blood transfusion

CLASSIFICATIONS

• Based on severity – Asymptomatic remission – Mild to moderate – Moderate to severe – Severe fulminant • Based on the region of bowel affected – Ileocolitis (involvement of the ileum and colon)

– Regional enteritis (such as ileitis or colitis)

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis as needed • Stress dose steroids should be considered if the patient has been treated for more than 2 weeks within the past 6–12 months to avoid manifestations of adrenal insufficiency. Steroids with glucocorticoid and mineralocorticoid activity should be administered (e.g., hydrocortisone). INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on type of surgery, patient wishes, and surgeon’s preferences. • Neuraxial placement may be contraindicated if coagulation studies are abnormal. • Hyperalimentation is usually continued in the intraoperative period. If stopped, hypoglycemia may result. Monitors

• Standard ASA monitors • Foley catheter in long cases, patients with suspected hypovolemia, or anticipated large fluid shifts • Foley catheter may be indicated for long cases, anticipated large fluid shifts, or hypovolemic patients. • Consider central venous catheter with central venous pressure for fluid management, as appropriate. Induction/Airway Management

• In hypovolemic patients consider adequate preoperative fluid hydration prior to induction. • Etomidate or ketamine can be useful in hypovolemic patients; have vasopressors available. • In anemic patients, consider having blood available or transfuse prior to induction. • To avoid additional oral trauma, perform gentle laryngoscopy and intubation. • If aphthous ulcers are present, may avoid leaving a bite block in the mouth.

Maintenance

• Muscle relaxation can aid surgical exposure and closure of abdominal fascia for bowel surgery • Fluid management: Replace deficits with crystalloid and factor in insensible losses. Patients are at risk for significant third-spacing and bowel edema, especially due to low colloid oncotic pressures. This can make closure of abdominal incisions more difficult. • Low albumin levels due to malnutrition: Adjust medication doses appropriately, particularly with highly protein-bound drugs. Unbound, free drug is pharmacologically active, and is also available for metabolism. Thus, consider smaller boluses and more frequent dosing.

Additionally, hypoalbuminemia may result in increased total body water and volume of distribution. • Consider avoiding nitrous oxide for bowel surgery as it can cause the bowel to expand and make fascial closure more difficult. • Chronic steroid use may result in diabetes; intraoperative glucose management may require insulin administration. • Intractable intraoperative hypotension may be due to adrenal insufficiency; treat with stress dose steroids. • Eye protection to avoid worsening ocular manifestations • Skin may be thin or easily breached from long-term steroid use; caution with positioning and tape for IV sites, endotracheal tube (ETT), and eyes.

Extubation/Emergence

Reversal of nondepolarizing muscle relaxants can help minimize weakness as patients often have underlying weakness due to malnutrition and electrolyte disturbances.

POSTOPERATIVE CARE BED ACUITY

Telemetry if the patient has severe electrolyte derangements. MEDICATIONS/LAB STUDIES/CONSULTS

• Consider epidural or patient-controlled analgesia (PCA) for postoperative pain control for large bowel resections or exploratory laparotomies. • Avoid ketorolac and NSAIDs due to metabolic bone disease. • Consider postoperative CBC

COMPLICATIONS

Hyperalimentation can result in hypo/hyperglycemia, hyperchloremic metabolic acidosis, fluid overload, electrolyte abnormalities, renal and hepatic dysfunction

REFERENCES

1. Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004;126(6):1504–1517. 2. Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007;5(12):1424–1429. 3. Abraham C, Cho JH. Inflammatory bowel disease. N Eng J Med. 2009:361(21):2066–2078. 4. Baumgart DC, Sandborn WJ. Inflammatory bowel disease: Clinical aspects and established and evolving therapies. The Lancet. 2007;369(9573):1641–1657. 5. National Digestive Diseases Information Clearinghouse Slattery E, Keegan D, Hyland J, et al. Surgery Crohn’s disease, and the biological era: Has there been an impact? J Clin Gastroenterol Dec 3 2010, E print.

See Also (Topic, Algorithm, Electronic Media Element) • Ulcerative colitis • Insensible fluid losses

CODES ICD9 • 555.0 Regional enteritis of small intestine • 555.1 Regional enteritis of large intestine • 555.9 Regional enteritis of unspecified site ICD10

• K50.00 Crohn’s disease of small intestine without complications • K50.10 Crohn’s disease of large intestine without complications • K50.90 Crohn’s disease, unspecified, without complications

CLINICAL PEARLS

• Crohn’s disease can cause weakness due to electrolyte abnormalities and malnutrition that can affect anesthetic management and require special perioperative management. • Patients often present for colectomy, proctolectomy, wound biopsy, incision/drainage, irrigation, and debridement; urgent surgery for actual or impending perforation.

CRYOPRECIPITATE Kenichi A. Tanaka, MD, MSc Satoru Ogawa, MD

BASICS DESCRIPTION

• Cryoprecipitate is a blood product derived from plasma and used for supplying clotting factors to a volume-sensitive patient. • Transfusion of cryoprecipitate is mainly indicated for the treatment of congenital defects of: – Factor VIII (FVIII) – von Willebrand’s factor (vWF) – Factor XIII (FXIII) – Fibrinogen – Fibronectin • A cross-matching is not required, but ABO compatibility should be considered before transfusion. PHYSIOLOGY PRINCIPLES

• Normal coagulation is dependent on several components: – Fibrinogen is converted to fibrin by thrombin. Fibrin is a polymerized protein that is involved in clot formation. – FVIII and vWF mediate adhesion of circulating platelets to exposed subendothelium. – FXIII promotes clot stability by forming covalent bonds between fibrin monomers and by cross-linking alpha-2 antiplasmin, fibrinogen, fibronectin, collagen, and other proteins to enhance the mechanical strength of the fibrin clot and protect the clot from proteolytic degradation. • Cryoprecipitate preparation – A unit of fresh frozen plasma (FFP) is thawed at 1–6°C. – Supernatant is the precipitated, cold-insoluble material that initially thaws. – It is resuspended in a small volume of plasma (10–15 mL). • Freezing – The resuspended fraction is refrozen at −18°C. – The time should be minimized from attainin the supernatant and freezing. • Storage – Up to 12 months • Contents (about 15 mL per unit) – Fibrinogen: ∼350 mg – FVIII: ∼150 units; increased when the donor has higher baseline levels (e.g., postexercise) – vWF: ∼150 units ADAMTS13 (a vWF cleaving protease) is minimal in cryoprecipitate. – FXIII

• Thawing cryoprecipitate – Requires ∼45–60 minutes – After thawing, cryoprecipitate should be administered within 4 hours. • ABO compatibility – Not required, but should be considered before transfusion. The plasma used to reconstitute the cryoprecipitate may contain a small amount of RBCs. Incompatible ABO cells will likely be cleared without undue consequences and sensitization to Rh is unlikely; however, with larger volumes, it may become problematic. • Duration of effect – Fibrinogen: 70–100 hours – FVIII: 12 hours – vWF: 10–24 hours – FXIII: 120–200 hours • Special handling – Administer through a 180–260 μm standard blood tubing. – Consider mixing with 10–15 mL of normal saline to ensure complete removal of all material from each bag. PHYSIOLOGY/PATHOPHYSIOLOGY

• Complications of cryoprecipitate administration: – Transfusion-related acute lung injury (TRALI) is caused by anti-HLA antibodies present in donor plasma. The risk appears to be lower with cryoprecipitate compared to FFP. – Possible worsening of disseminated intravascular coagulation and organ dysfunction by forming fibrin in microcirculations. – Viral transmission. The risks of viral transmission, particularly hepatitis C and human immunodeficiency virus, have been significantly reduced by the nucleic acid testing of donor blood. – Acute hemolytic transfusion reaction, nonhemolytic febrile and allergic reactions, or thrombosis have been reported; however, their occurrence is rare. – Venous and arterial thromboembolic complications should be cautioned because cryoprecipitate rapidly increases plasma fibrinogen, FVIII, FXIII, and vWF. – Hypocalcemia may result from massive transfusion due to citrate overload. – Platelet microparticles can play an active role in thrombosis, inflammation, and vascular reactivity. • Human-derived fibrinogen is a potential alternative; however, adverse events include thrombotic complications and anaphylactic reactions.

PERIOPERATIVE RELEVANCE

• Cryoprecipitate rapidly increases plasma levels of fibrinogen, FVIII, FXIII, and vWF, which collectively exert hemostatic activity. Indications include the following (1): – Congenital fibrinogen deficiency, von Willebrand’s disease, congenital FXIII deficiency for prevention (perioperative and peripartum), as well as treatment of bleeding. When possible, however, hereditary deficiencies of FVIII, FXIII, and vWF should be managed with virally inactivated human-derived products or recombinant products. – Massive transfusion with microvascular bleeding and fibrinogen <80–100 mg/dL. If

fibrinogen measurement cannot be performed in a timely manner, clinical decisionmaking may warrant administration of cryoprecipitate (2). – Hemorrhage after cardiac surgery if fibrinogen level is below 150 mg/dL. – Hemorrhage secondary to thrombolytic therapy – Management of bleeding due to snake venom – Iatrogenic premature rupture of amniotic membranes – Amniotic fluid embolism – Uremia; prevention and treatment of bleeding – Fibronectin deficiency after major surgery, trauma, burns, and sepsis. Deficiency impairs the reticuloendothelial system from clearing particulate debris in the circulation resulting in the accumulation of fibrin microaggregates, collagenous debris, and immune complexes. – Topical use as in fibrin glue (virally inactivated human-derived fibrin sealant products are preferred) • Cryoprecipitate has the benefit of causing less hemodilution and thrombocytopenia after infusion compared to FFP. See Table • Large amounts of shed blood processed in the cell salvage system can deplete plasma fractions including fibrinogen. • Fibrinogen measurements by the Clauss method may be falsely elevated after large amounts of hydroxyethylstarch infusion. • Thromboelastography/metry can be used to guide fibrinogen replacement (3).

EQUATIONS

For fibrinogen replacement therapy, one unit of cryoprecipitate per 10 kg body weight increases plasma fibrinogen by ∼50 mg/dL in the absence of continued consumption or massive bleeding. To increase it to 100 mg/dL, the required number of cryoprecipitate is 0.2 x weight (kg).

REFERENCES

1. ’Shaughnessy DF, Atterbury C, Bolton Maggs P, et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate, and cryosupernatant. Br J Haematol. 2004;126:11–28. 2. Hiippala ST, Myllylä GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg. 1995;81:360–365. 3. Tanaka KA, Ogawa S, Bolliger D. A primer for clinical use of rotational thromboelastometry. Point of Care. 2012;11:77–84. See Also (Topic, Algorithm, Electronic Media Element) • Fibrinogen • Fresh frozen plasma (FFP) • Transfusion-related lung injury (TRALI) • Blood transfusion infection

CLINICAL PEARLS

• Fibrinogen replacement with cryoprecipitate is preferred to FFP because of a lower volume of transfusion, and lower incidence of TRALI. • Compared to purified human fibrinogen, cryoprecipitate provides clinically relevant amounts of FXIII. • Assuming normal fibrinogen level at baseline, a critical level (1 g/L) of fibrinogen is reached after a loss of about 1.4 times the blood volume. • For hereditary deficiency of FVIII, FXIII, or vWF, plasma-derived or recombinant factor concentrate is available and is preferred to cryoprecipitate for improved safety.

CRYSTALLOIDS Trent Emerick, MD James Cain, MD

BASICS DESCRIPTION

• Crystalloids are solutions of water, electrolytes, and other nonprotein solutes. They are administered for volume replacement and expansion, electrolyte replacement, as a medication carrier, and for dilution of blood products during transfusion to decrease viscosity. • Benefits include: Inexpensive, easy to store, long shelf–life, readily available, few adverse actions, available in a variety of formulations, do not require special compatibility testing, and there are no religious objections to their use. • Crystalloids may be classified as hypertonic, isotonic, or hypotonic with respect to plasma osmolarity; some may also be described as “balanced” or “physiological” solutions with regard to their chloride concentration relative to plasma; unbalanced fluids have a proportionally high chloride concentration. PHYSIOLOGY PRINCIPLES

• Average 70 kg man has 42 L of total body water (TBW). The intracellular volume has 28 L (67% of TBW); the interstitial volume has 10.5 L (25% of TBW); and the intravascular volume has 3.5 L (8% of TBW). • Electrolyte solutions distribute through these spaces; ∼1/3rd to 1/4th will remain in the intravascular space following isotonic administration. • Normal saline (0.9% NaCl); “unbalanced” solution – Sodium 154 mEq/L; greater than plasma – Chloride 154 mEq/L; significantly greater than plasma – Osmolarity 308 mEq/L; slightly greater than serum osmolarity (∼285 mOsm/L). • Lactated Ringer’s; “balanced” solution. pH 6.5 – Sodium 130 mEq/L; less than plasma – Chloride 109 mEq/L; slightly greater than plasma – Potassium 4 mEq/L; similar to plasma – Calcium 3 mEq/L; similar to plasma – Lactate 28 mEq/L; hepatically metabolized to glycogen that is then oxidatively metabolized to CO2 and H2O. The CO2 accepts a hydrogen ion (H+) to yield bicarbonate.

Thus, lactate functions as an alternative source of bicarbonate. However, because the conversion takes ∼1–2 hours, depending on the integrity of cellular oxidative processes, it is a less effective source of bicarbonate in lactic acidosis, shock, or decreased perfusion states. – Osmolarity: 275 mOsm/L; slightly less than plasma, hence hypotonic • Normosol; “balanced.” pH 7.4

– Sodium 140 mEq/L; similar to plasma – Chloride 98 mEq/L; similar to plasma – Potassium 5 mEq/L; slightly greater than plasma – Magnesium 3 mEq/L; Mg++ is the second most plentiful cation of intracellular fluid and plays an important role as a cofactor for enzymatic reactions and in neurochemical transmission and muscular excitability. – Acetate 27 mEq/L; CH3COO− is metabolized in the liver (even in severe disease) to

become a source of H+ acceptors. Thus, it is an alternate source of bicarbonate. – Gluconate 23 mEq/L; a theoretical alternate metabolic source of bicarbonate ion. However, a significant antiacidotic action has not been established. Thus, the gluconate anion serves primarily to complete the cation–anion balance of the solution. – Osmolarity 295 mOsm/L; greater than plasma • Plasmalyte; “balanced” solution – Sodium 140 mEq/L; similar to plasma – Chloride 98 mEq/L; similar to plasma – Potassium 5 mEq/L; slightly greater than plasma – Magnesium 3 mEq/L – Acetate 27 mEq/L; serves as a bicarbonate alternative or precursor – Gluconate 23 mEq/L; a theoretical alternative to bicarbonate – Osmolarity 294 mOsm/L; slightly greater than plasma • Hypertonic saline 3%; pH 4.5–7 – Sodium 513 mEq/L – Chloride 513 mEq/L – Osmolarity 1,027 mOsm/L; the hypertonicity creates an osmotic gradient for fluid to shift from the intracellular to interstitial and intravascular space, resulting in an increase in preload. It can also cause vasodilation from direct vascular smooth muscle relaxation with resultant improvement in capillary blood flow. Furthermore, hypertonicity can decrease endothelial cell volume (intracellular to extracellular flow) that increases capillary diameter and decreases vascular resistance. • Dextrose 5% in water; D5W. pH 4.5 – Dextrose 50 g/L; promotes glycogen deposition and decreases or prevents ketosis if sufficient doses are provided. – Osmolarity “inactive;” glucose is metabolized as an energy source and there is no sodium. Thus, the net effect is equivalent to giving pure water that is distributed throughout TBW with each compartment receiving fluid in proportion to TBW. A large percentage moves intracellularly.

ANATOMY

• Plasma electrolytes pass freely between the intravascular space and interstitial fluid. Plasma proteins are restricted to the intravascular space. Because of its abundance, sodium is the most important osmolar force in the interstitial space. Potassium and intracellular proteins are the most important oncotic forces in the intracellular space. • The renin-angiotensin system affects cardiac output, BP, and fluid status. It is activated by decreased BP in the renal artery, decreased plasma sodium levels at the macula densa,

and/or the surgical stress response. • Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are proteins released by the cardiac atria and ventricles, respectively, when the chamber walls are distended due to increased volume and pressure. These peptides increase the glomerular filtration rate (GFR), sodium excretion, and water excretion. BNP is also utilized as a marker for congestive heart failure. • Sympathetic nervous system fibers exit the spinal cord at the T1–L2 level. Neuraxial blockade induced sympathectomy occurs when T1–L2 fibers are blocked causing peripheral dilation and hypotension. Fluid is commonly administered for this perturbation. • A neuraxial block affecting T1–T4 fibers affects the cardioaccelerator fibers and blunts the tachycardic response to hypotension. Fluid is commonly administered for this perturbation.

DISEASE/PATHOPHYSIOLOGY

• Normal saline – Nongap hyperchloremic metabolic acidosis; previously believed to be secondary to “dilutional acidosis.” NaCl dissolves into NaOH and HCl in plasma. The 154 mEq/L of chloride found in normal saline is much greater than that of plasma (100 mEq/L). This results in more hydrochloric acid as compared to sodium hydroxide and causes acidosis (1)[C]. NaCl + H2O ←→→ HCl + NaOH. Additionally, normal saline lacks a buffering

salt such as lactate or acetate and bicarbonate is eliminated renally to maintain electrical neutrality. • Lactated Ringer’s – In acidotic and anoxic states, lactate metabolism is affected. – Hyperkalemia can be worsened – Cannot be administered with blood products; calcium in solution can clot blood products. – Respiratory acidosis from carbon dioxide production can occur. – Mild hyponatremia – May be associated with panic attacks secondary to the complexing of calcium, despite the absence of serum levels or symptoms of hypocalcemia. • Normosol and Plasmalyte – Hyperkalemia can be worsened – Cautious use with metabolic or respiratory alkalosis; the bicarbonate alternatives, acetate and gluconate, can exacerbate – Severe hepatic insufficiency may preclude the conversion of acetate and gluconate. – Dilutional hyponatremia • D5W can cause hyperglycemia and hypotonicity. Hypotonicity can affect intracellular volume and cause cell lysis. • Hypertonic saline – Central myelinolysis can result from the rapid increase in sodium. May be avoided by limiting sodium increases to a maximum rate of 0.5 mEq/L/hour, not to exceed 10–12 mEq/L in 24 hours. – Renal insufficiency and failure are seen with a higher incidence than with other crystalloids. – Hemorrhage secondary to excessive fluid resuscitation

– Decreases in afterload can result; transient hypotension can be seen after boluses are administered. – Dilution of plasma constituents (coagulation factors) can occur with rapid intravascular volume expansion. – Hypokalemia or hyperchloremic acidosis – Rebound increases in ICP after boluses or when continuous infusions are stopped. – Phlebitis or tissue necrosis can result from hypertonicity; central lines are preferable. • Anesthesia blunts the normal sympathetic tone and physiologic response to hypovolemia. • Transurethral resection of the prostate (TURP) syndrome refers to hypotonic hypervolemic hyponatremia due to absorption of the free water surgical field irrigant during a TURP procedure. This can lead to sodium levels <125 mEq/L and symptoms of hyponatremia (neurologic symptoms, including seizures, confusion, lethargy) (2)[A]. • Overly aggressive fluid replacement can lead to the development of pulmonary edema and impaired oxygen/carbon dioxide exchange, particularly in patients with compromised cardiac performance such as neonates and the elderly.

PERIOPERATIVE RELEVANCE

• Crystalloid versus colloid resuscitation: Crystalloids are significantly less expensive. Resuscitation requiring volume replacement does not show a benefit of colloids over crystalloids (3)[A]. • SAFE study: Prospective randomized controlled trial comparing colloids versus crystalloids for fluid resuscitation in critical care patients: No significant difference is found in clinical outcome between colloid and crystalloid groups (4)[A]. • Normal saline. Hyperchloremic acidosis has been shown to decrease mucosal perfusion, profoundly affect eicosanoid release in renal tissue that leads to vasoconstriction and decreased GFR, inactivate membrane calcium channels, and inhibit norepinephrine release from sympathetic nerve fibers resulting in redistribution of cardiac output away from internal organs. Attempts to correct this abnormality may actually be the main adverse effect. Acidosis is often seen as a reflection of poor organ perfusion or poor myocardial function. A negative base excess may prompt more saline boluses containing fluids that exacerbate acidosis, the use of blood products, escalation of inotropic support, and initiation of ventilator support. Furthermore, when coupled with acidosis from a different source (e.g., lactic acidosis from tissue hypoperfusion) this can further complicate the management of patient care. • Hypertonic saline. May be useful in cerebral edema, burn injuries, or trauma; outcome studies are currently underway. – Cerebral edema. Increased osmolarity can draw fluid from brain cells into the intravascular space; this results in decreased cerebral water content, edema formation, and ICP. Increased intravascular volume may lead to an autoregulatory decrease in intracerebral blood volume (assuming autoregulation remains intact). Studies have demonstrated improved survival in traumatic brain injury. – Burn injuries. The physiochemical interaction with glycocalyx may result in a less “leaky” vascular endothelium. Studies have shown that severe burns have a decreased incidence of abdominal compartment syndrome, possibly from decreased capillary leak (less bowel wall and intra-abdominal fluid accumulation)

– Trauma. Can increase BP with small volume resuscitation and may increase survival. This is attributed to the avoidance of hemodilution seen with excess amounts of isotonic fluids, hypothermia, acidosis, coagulopathy, and sustained hyperosmolar state.

EQUATIONS

• Plasma osmolarity (mOsm/L) = ([Na+] × 2) + (BUN/2.8) + (glucose/18) where BUN and glucose are mg/dL (normal plasma osmolarity ∼285 mg/dL) • Maintenance fluids can be administered using the 4-2-1 rule: 4 mL/kg/hr for first 10 kg, 2 mL/kg/hr for next 10 kg, and 1 mL/kg/hr for each kg above 20 kg. • Fluid deficit calculations. Initial fluid deficit due to NPO status: Number of hours NPO × maintenance rate, administer ½ during the first hour of procedure, 1/4 during the second hour, and 1/4 during the third hour. Third spacing/evaporative surgical field losses should be corrected at 0–10 mL/kg/hr depending on the degree of tissue exposure (e.g., 2–4 mL/kg/hr for open cholecystectomy and 4–8 mL/kg/hr for bowel resection). Replace blood loss with crystalloid fluid in a 1:4 ratio until transfusion of blood products is indicated. • Free water deficit (useful with hypernatremia) = 0.6 × (weight in kg) × ([serum sodium/140]–1). Can replace deficit over 2–3 days with free water enterally, or with isotonic/hypotonic solutions intravenously.

REFERENCES

1. Kellum JA. Saline-induced hyperchloremic metabolic acidosis. Crit Care Med. 2002;30(1):259–261. 2. Gravenstein D. Review article: Transurethral resection of the prostate (TURP) syndrome: A review of the pathophysiology and management. Anesth Analg. 1997;84(2):438–446. 3. Hartog C, et al. Review article: The efficacy and safety of colloid resuscitation in the critically Ill. Anesth Analg. 2011;112:156–164. 4. SAFE study: A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350:2247–2256.

ADDITIONAL READING

• Chappell D, et al. A rational approach to perioperative fluid management. Anesthesiology. 2008;109:723–740. • McGee S, Abernethy WB 3rd, Simel DL. The rational clinical examination. Is this patient hypovolemic? JAMA. 1999;281(11):1022–1029. • Shafiee MA, Bohn D, Hoorn EJ, et al. How to select optimal maintenance intravenous fluid therapy. QJM. 2003;96(8):601–610.

See Also (Topic, Algorithm, Electronic Media Element) • Colloids • Insensible fluid losses • Plasma osmolarity • TURP syndrome

CLINICAL PEARLS

• Lactated Ringer’s solution should not be used as diluents for packed red blood cells because the calcium in this fluid can bind to the citrated anticoagulant in the packed cells, inactivate the anticoagulant, and promote clot formation in the donor cells. • Lactated Ringer’s solution and Plasmalyte contain potassium and should not be used in patients with hyperkalemia or in patients at risk of hyperkalemia such as in renal failure.

CUSHING’S REFLEX Steve Wang, MD

BASICS DESCRIPTION

• Rapid increases in intracranial pressure (ICP) can lead to a central nervous compensatory response which results in an increase in sympathetic tone and hypertension, with a reflexive bradycardia and irregular respirations. PHYSIOLOGY PRINCIPLES

• The brain utilizes ∼20% of the total body oxygen consumption. Oxygen is required for the maintenance of depolarization and repolarization activity necessary for executive function, autonomic processes, and reflexes; as well as for cell homeostasis. – Cerebral blood flow (CBF) is ∼45–55 mL/100 g/minute. – Cerebral metabolic rate is ∼3–3.5 mL/100 g/minute and describes the amount of oxygen utilized. – No oxygen or glucose storage is present and a continual, adequate supply is necessary to provide adequate function. – Cerebral autoregulation serves to maintain a constant flow of blood (and constant supply of oxygen and glucose) within a range of mean arterial pressures. ANATOMY

The constituents of the cranium include the following: • Brain tissue • Cerebrospinal fluid (CSF) • Blood

PHYSIOLOGY/PATHOPHYSIOLOGY

• The cranium is a rigid structure that contains a fixed volume of brain tissue, blood, and CSF. Initially, an increase in the volume in one of the constituents is compensated by a decrease in another; this serves to avoid elevations in ICP. This compensatory response is limited, however; beyond a certain point, small changes in volume can result in significant increases in pressure. • Increases in cranial volume can result from – Brain tissue: Tumor, edema (ischemic stroke, cerebral contusion), trauma (epidural hematoma, subdural hematoma, cerebral contusion), pseudomotor cerebri – CSF: Hydrocephalus – Blood: Hypoxia, hypercarbia, obstruction of venous return from head position, Valsalva maneuvers or increased intrathoracic pressures (coughing, gagging, excessive PEEP), seizures, severe hypertension, hypotension (vasodilation to maintain cerebral blood flow can increase cerebral blood volume)

• Abrupt or excessive increases in intracranial volume can cause increased ICP with resultant decreases in the cerebral perfusion pressure (CPP). CPP = MAP–ICP. A decrease in the CPP can impair oxygenation and delivery of substrate. – A CPP <15 mm Hg always results in a Cushing’s reflex. – A CPP between 15 and 30 mm Hg typically results in its occurrence. – A CPP between 30 and 45 mm Hg almost never results in its occurrence. • Reflex bradycardia. Increased BP stimulates the carotid sinus, a baroreceptor within the carotid arteries, resulting in a reflexive bradycardia. • Other – Pressure exerted on the medulla of the brainstem may cause irregular respirations. – Cardiac output initially increases in its attempt to restore cerebral perfusion pressure.

PERIOPERATIVE RELEVANCE

• The manifestation of these signs suggests the presence of cerebral ischemia from increased ICP and impending brain herniation, which can be fatal. • Immediate medical/surgical attention is warranted to re-establish cerebral blood flow. – Intubation with hyperventilation to a PaCO2 of 30–35 mm Hg. Decreases in PaCO2

alkalinize the CSF and cause cerebral vasoconstriction. Although the effect is limited (11– 20 hours), it is one of the fastest techniques to reduce ICP. Avoid excessive hyperventilation (PaCO2 <25 mm Hg), as it can contribute to cerebral ischemia.

– Elevation of the head of the bed facilitates cerebral venous drainage to the right atrium – Propofol decreases CBF and CMR – Mannitol 0.25–1.0 g/kg can decrease the ICP within 1–5 minutes (peak effect 20–60 minutes, duration up to 6 hours). It is a hyperosmolar agent that draws water from neurons across the blood brain barrier into the intravascular space. The effect is a reduction in intracranial volume, and hence ICP. – Hypertonic saline, similarly, creates an osmotic gradient for intracerebral fluid to shift intravascularly. Additionally, it may be used in hypotensive and hypovolemic patients to expand intravascular volume. – CSF drainage is a quick and reliable method to lower the ICP. A ventriculostomy has the advantage of being therapeutic and diagnostic. – Craniotomy to remove the inciting cause. Medical management should be aggressively continued en route to the operating room. • Cushing’s reflex is a compensatory response to offset impaired cerebral perfusion pressure. Cushing’s triad consists of – Hypertension. Systolic BP is primarily increased and widens the pulse pressure. – Bradycardia. A “late” reflex. Often, tachycardia may first be observed from the initial sympathetic response (2). – Irregular respirations. Under general anesthesia or with an intubated and mechanically ventilated patient, this may not manifest or be obvious. • The use of total intravenous anesthesia (TIVA) may make the detection of a relative bradycardia more difficult to detect.

EQUATIONS

CPP = MAP – ICP, where CPP is cerebral perfusion pressure, MAP is mean arterial pressure, and ICP is intracranial pressure.

REFERENCES

1. yling J. Managing head injuries. Emerg Med Serv. 2002;8:42.

2. Kalmar AF, Van Aken J, Caemaert J, et al. Value of Cushing reflex as warning sign for brain ischemia during neuroendoscopy. Br J Anaesth. 2005;94(6):791–799. 3. Molnar C, Nemes C, Szabo S, et al. Harvey Cushing, a pioneer of neuroanesthesia. J Anesth. 2008;22(4):483–486. 4. Hwang Wan W, Ti Ang B. The Cushing response: A case for its role as a physiological reflex. J Clin Neurosci. 2008;15(3):223–228.

ADDITIONAL READING

• Kosieradzki M, Rowinski W. Ischemia/reperfusion injury in kidney transplantation: Mechanisms and prevention. Transplant Proc. 2008;40(10):3279–3288. See Also (Topic, Algorithm, Electronic Media Element)

• Intracranial hypertension • Cerebral blood flow

CLINICAL PEARLS

• Marked increases in intracranial volume may lead to an increase in ICP; this can compromise cerebral blood flow and cause cerebral ischemia. • The Cushing’s reflex is the activation of sympathetic tone elicited by the increase in ICP in an effort to restore cerebral perfusion. Thus, it is also an indicator of severe intracranial ischemia and suggests impending brain herniation. Identification of the Cushing’s reflex by its signs warrants immediate medical/surgical intervention; death can ensue within minutes. • Studies have suggested, however, that hypertension and tachycardia can offer an earlier and more reliable warning sign of increased ICP (2). • With sustained moderate increases in ICP, the decreased CPP leads to the development of plateau waves on ICP monitors. When the Cushing’s reflex is activated, it abolishes the plateau waves by increasing CPP.

CUSHING’S SYNDROME Matthew D. Cohen, DO

BASICS DESCRIPTION

• Cushing’s disease refers specifically to hypercortisolism caused by adrenocorticotropic hormone (ACTH)-secreting pituitary tumors, usually microadenomas • Cushing’s syndrome, however, is the constellation of symptoms resulting from high levels of circulating cortisol in the body; it refers to hypercortisolism from all causes. The syndrome was first described in 1912 by Dr. Harvey Cushing. • Patients with Cushing’s syndrome commonly present to the operating room for corrective surgery to remove pituitary tumors, lung tumors, adrenal tumors or adrenalectomies, or may present for surgical procedures unrelated to the syndrome. EPIDEMIOLOGY Incidence

• In the US, it is estimated that 10–15 per million people per year will develop Cushing’s syndrome. • Another study (2) estimated the incidence of cushing’s disease as only 2.4 per million and noted that there was an increase between 1975 and 1992.

Prevalence

• 39.1 per million inhabitants. • Gender: More common in females than males (15:1) • Age: commonly between 25 and 40 years

Morbidity

• Cushing’s syndrome predisposes to high rates of cardiovascular disease and hypertension, even after a surgical “cure.” • Other complications include osteopenia, impaired reproductive and sexual function, diabetes, depression, and skeletal muscle wasting. Mortality

• There is a four-fold higher mortality rate than age- or gender-matched cohorts (2). • Once an adrenal adenoma is removed, the cure rate is 100%; however, most patients with adrenal carcinoma die within 2 years of diagnosis. ETIOLOGY/RISK FACTORS

• Chronic exogenous corticosteroid therapy • ACTH oversecretion from tumor-related syndromes is responsible for 80–85% of cases. They most commonly result from pituitary adenomas (Conn’s syndrome) but can also be seen

with oat cell lung cancers or other ACTH or corticotrophin-releasing hormone (CRH) producing tumors. • ACTH-independent tumors are responsible for 15–20% of cases and may be from unilateral or bilateral adrenal adenoma or carcinoma.

PATHOPHYSIOLOGY

• CRH release is triggered by stressors such as fever, surgery, burns, exercise, psychological stress, and hypotension. CRH, stimulates ACTH release from the pituitary gland into the bloodstream; in turn, ACTH stimulates cortisol release by the adrenal glands. • Cortisol has a normal diurnal variation, highest from 5 to 9 am and lowest from 6 pm to midnight. • Cortisol affects gluconeogenesis as well as fat and protein metabolism; suppresses the immune system; increases myocardial contractility and output; and enhances the catecholamine pressor effect. • Abnormally elevated cortisol levels can cause (1) – BP elevation from deoxycorticosterone and increased vascular sensitivity to circulating vasopressors. – Vascular disease; prolonged hypertension may lead to vascular functional abnormalities. – Increased gastric acid secretion via increased pepsin levels. – Decreased collagen synthesis – Osteoporosis; inhibits osteoblast function and intestinal calcium absorption. – Hyperglycemia; increases glycogen synthase that increases hepatic glucose output and also decreases insulin sensitivity. – Hypokalemia can result from potassium wasting secondary to the triggering of a mineralocorticoid response in the kidneys. – Water retention from an increase in mineralocorticoids. – Muscle weakness; induces catabolic changes in muscle and decreases muscle protein synthesis as well as type II muscle fibers. – Hypercoagulability may be partially due to alterations of von Willebrand factor and hyperresponsiveness of platelets (3). – Immune suppression: may cause leukocytopenia and can inhibit the immune/inflammatory response to injury.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess for concomitant diseases including diabetes mellitus and cardiac or vascular disease (4). • Difficulty with ventilation or intubation may be encountered; perform a careful airway exam (4). • In patients with Cushing’s syndrome from exogenous steroid use, evaluate the underlying disease for anesthetic implications (e.g., cervical spine instability in patients with rheumatoid arthritis, electrolyte imbalances and dehydration in Crohn’s and ulcerative colitis, etc). • Perioperative thrombus risk is increased due to hypercoagulability.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Frequent infections due to a relatively immunocompromised state (high levels of cortisol and elevated blood sugar) • Edema due to sodium and water retention • Rapid onset of weight gain

History

• If secondary to chronic steroid use, determine the indication and status of the comorbidities (e.g., systemic lupus, etc) • Chronic or repeated steroids may be used in the treatment of some chronic pain conditions.

Signs/Physical Exam

• Facial adiposity (moon facies), darkened skin with purple striae, acne, cervicodorsal fat deposits (buffalo hump), hirsutism, edema • Elevated blood glucose • Muscle weakness • Hypertension

TREATMENT HISTORY

“Stress dose” steroids may be necessary in patients undergoing surgery and who have been on chronic steroid therapy. MEDICATIONS

• Patients with Cushing’s syndrome are often on medications to inhibit adrenal steroid production (4). • Ketoconazole: Midazolam levels and effects may be increased; fentanyl levels may be increased and result in delayed emergence or other adverse effects; and lidocaine systemic levels may be increased. • Metyrapone: Not as frequently used in the US but is quite common elsewhere. May cause edema and neurologic side effects. • Mitotane: The effects of benzodiazepines, opioids, and inhaled anesthetics may be potentiated; can result in increased CNS depression or other side effects. • Bromocriptine: Can inhibit ACTH release. When combined with phenylephrine or other sympathomimetics may cause hypertension, ventricular tachyarrhythmias, or seizures.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Blood glucose • Basic Metabolic Profile to evaluate for hypokalemia • EKG • If lung cancer is the underlying etiology of Cushing’s, a chest x-ray/CT should be reviewed to evaluate thoracic and airway anatomy.

Pregnancy Considerations

• Diagnosing Cushing’s syndrome in pregnancy is difficult because of the natural changes in the hypothalamic-pituitary-adrenal axis that occur with pregnancy. • Pregnancy also can commonly result in weight gain, edema, possibly hypertension, or elevation of blood glucose.

CONCOMITANT ORGAN DYSFUNCTION • Vascular and cardiac disease • Diabetes mellitus • Hypertension • Hypercoagulability

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Uncontrolled hyperglycemia • Abnormal EKG that may require further cardiac workup • Hypertensive crisis • Severe hypokalemia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines and opioids may be potentiated by home medications. • Perioperative antacids/H2 blockers should be considered. • DVT prophylaxis should be considered.

Special Concerns for Informed Consent

• If risk factor for a difficult airway are present, a thorough discussion of airway management options and risks, including an awake, fiberoptic intubation, and possible emergent tracheostomy should take place • Patients with significant muscle weakness should be informed of the risk of prolonged postoperative intubation/ventilation. INTRAOPERATIVE CARE Choice of Anesthesia

• General or regional anesthetic techniques are both considered • General endotracheal anesthesia is required for hypophysectomy or adrenalectomy surgeries • Since many patients will be on anticoagulants for DVT prophylaxis, neuraxial anesthesia may be contraindicated. Monitors

• Neuromuscular twitch monitoring if muscle relaxants are used. • Additional intraoperative monitors are chosen based on the patient’s cardiovascular and

other comorbidities as well as the expected extent or type of surgery being performed.

Induction/Airway Management

• If there are no signs of a potentially difficult airway, a standard of rapid sequence induction and intubation are appropriate. • If a difficult airway is suspected, consider an awake fiberoptic intubation, indirect video laryngoscopy, or other method as an initial attempt.

Maintenance

• Great care must be taken when positioning patients with osteoporosis as fractures may occur. • Doses of muscle relaxants should be decreased in patients with muscle weakness. • Even if muscle relaxants are not used, mechanical ventilation may be recommended due to the possibility of muscle weakness and inadequate ventilation.

Extubation/Emergence

• Ensure adequate respiratory muscle strength prior to extubation by assessing tidal volumes and/or NIF • Delayed emergence, hypotension, and confusion may be signs of steroid deficiency or Addisonian crisis after removal of an ACTH-secreting tumor. • Delayed emergence may also be caused by potentiation of opioids or benzodiazepines due to the patient’s home medications.

POSTOPERATIVE CARE BED ACUITY

Telemetry or intensive care unit (ICU) for adrenal gland removal may be considered depending on blood loss, intraoperative events, or other comorbidities. MEDICATIONS/LAB STUDIES/CONSULTS

• Close monitoring of BP and blood glucose are recommended. • If surgery is for removal of a pituitary adenoma, postoperative steroid replacement must be given for 3–14 months after surgery or until endogenous steroid synthesis normalizes. • Endocrinology consult may be warranted for evaluation and treatment postoperatively.

COMPLICATIONS

• Hypercortisolism causes hypercoagulability and DVT risk is higher in patients with Cushing’s syndrome (4). • Diabetes insipidus is a possible complication of pituitary resection. • New neurological deficits or pituitary hormonal insufficiency are possible. • Postoperative mortality from pituitary surgery may reach 2% (4).

REFERENCES

1. Arnaldi A, et al. Diagnosis and complications of Cushing’s syndrome: A consensus statement. J Clin Endocrinol Metab. 2003;88(12):5593–5602.

2. Etxabe J, Vasquez JA. Morbidity and mortality in Cushing’s disease: An epidemiological approach. J Clin Endocrinol. 1994;40:479–484. 3. Casonato A, et al. Abnormalities of von Willebrand factor are also part of the prothrombotic state of Cushing’s syndrome. Blood Coag Fibrinolysis. 1999;10:145–151.

4. Utz A, et al. Pituitary surgery and postoperative management in Cushing’s disease. Endocrinol Metab Clin N Am. 2005;34:459–478.

ADDITIONAL READING

• Melmed S. ed. Williams Textbook of Endocrinology, 12th edition. Philadelphia: Elsevier Inc. 2011. Chapter 15.

See Also (Topic, Algorithm, Electronic Media Element) • Diabetes mellitus • Hypokalemia • Cortisol • Hypertension

CODES ICD9 255.0 Cushing’s syndrome ICD10 E24.9 Cushing’s syndrome, unspecified

CLINICAL PEARLS

• Hypercortisolism can lead to multiple comorbid conditions with increased anesthetic risk (e.g., vascular disease, coronary disease, diabetes). • Be vigilant for signs of hypoadrenalism and steroid withdrawal in the immediate postoperative period after adrenalectomy or partial hypophysectomy • When performing adrenal carcinoma resection, ensure there is no pneumothorax prior to closure of the wound. This is a common complication, approaching 20% incidence.

CYANIDE POISONING Praveen Kalra, MBBS, MD, FCCP

BASICS DESCRIPTION

• Cyanide is a highly volatile liquid that has, in the past, been utilized as a chemical warfare agent. Today, it presents most commonly from fire smoke or nitroprusside administration. • Cyanide is a mitochondrial toxin that inhibits the activity of mitochondrial cytochrome oxidase, an enzyme necessary for normal cell respiration. As a result, it prevents cells from extracting and using oxygen from arterial blood. • Clinical manifestations and laboratory findings stem from an inability to utilize oxygen despite its presence or availability: “Starvation among plenty.” • Toxicity ranges from extremely rapid, with death occurring within minutes, to hours depending on the amount, route of exposure, and the length of time a person is exposed. EPIDEMIOLOGY Incidence

Estimates vary widely due to concurrent carbon monoxide poisoning. Morbidity/Mortality No clear data

ETIOLOGY/RISK FACTORS

• Smoke inhalation from fire is the most common cause of cyanide poisoning in developed countries. Hydrogen cyanide is produced from combustion of carbon-based and nitrogenbased materials; high concentrations are produced with plastic, polymer, synthetic fiber, wool, and silk substrates. Toxic and/or lethal concentrations are found in the blood in most fire victims. • Sodium nitroprusside (SNP) use; although newer drugs with safer profiles have reduced its use today, the ability to easily titrate to desired effect (quick onset and offset) make it an attractive option in certain cases. The risk of cyanide toxicity from SNP is increased with hypoalbuminemia, cardiopulmonary bypass procedures, and moderate-to-high doses. • Industrial exposure through metal extraction in mining, photography, electroplating in jewelry, plastics, and rubber manufacturing increases cyanide exposure. • Suicide or homicide attempts • Food like bitter almonds, peaches, pears, apples, and apricots are also responsible for cyanide poisoning. PHYSIOLOGY/PATHOPHYSIOLOGY

• Cyanide toxicity hinders aerobic respiration by inhibiting the final enzyme in the electron transport chain (ETC), known as cytochrome c oxidase.

• Normally, the ETC couples a reaction between an electron donor (NADH) and an electron acceptor (oxygen). The ETC is located in the mitochondrial inner membrane, and as the electron passes down the chain it generates a proton gradient and potential energy across the mitochondrial membrane. The potential energy is harnessed when the protons flow back across the membrane via adenosine triphosphate (ATP) synthase (down their gradient): ADP + H+ →ATP. • Normally, oxygen serves as the terminal electron acceptor at cytochrome c oxidase. In this manner, aerobic respiration is capable of producing 36 ATP from a single glucose molecule. • Cyanide molecules inhibit cytochrome c oxidase from reducing oxygen; it binds more tightly than oxygen to the ferric ion (Fe3+) binding spot. In doing so, it hinders the ETC, and hence oxidative phosphorylation. • Cells resort to anaerobic respiration (without oxygen); it is less efficient and produces only 2 ATP molecules in addition to lactic acid. • “Starvation among plenty.” Despite an ample oxygen supply, cells become hypoxic because they are incapable of utilizing the oxygen. • Additionally, cyanide also nonspecifically inhibits antioxidants (catalase, glutathione reductase, superoxide dismutase); this results in the accumulation of toxic oxygen-free radicals. Furthermore, it causes the release of glutamate and inhibits the enzyme glutamic acid decarboxylase (GAD), the enzyme responsible for the formation of GABA (thus reduces the seizure threshold). • SNP binds to the Fe3+ moiety in oxyhemoglobin to yield methemoglobin and SNP- . SNP- is a reduced and unstable molecule that spontaneously breaks down into 1 nitric oxide (therapeutic) and 5 cyanide (toxic by-product) molecules. This slow release of cyanide typically allows the body time to detoxify before it interferes with cellular respiration. Detoxificationcan occurs in two manners: – Methemoglobin (normally comprises 2% of all hemoglobin) binds to cyanide to yield cyanomethemoglobin (a non-toxic, non-oxygen carrying hemoglobin) – Thiosulfate binds to cyanide to yield thiocyanate via the rhodanese enzyme in the liver and kidneys. Thiosulfate levels can become exhausted with high blood concentrations of cyanide, high SNP dose, or low thiosulfate levels (e.g., malnutrition, postoperative states). Thus, it is the “rate-limiting" step for the development of cyanide toxicity. • Absorption. Cyanide is rapidly absorbed through the respiratory tract and mucus membranes. It can be absorbed through the GI tract and skin. Protein binding: 60%; Vd 1.5 L/kg.

PREVENTATIVE MEASURES

• When utilizing SNP, initial rates should not exceed 0.3 μg/kg/min, and maximum rates of 10 μg/kg/min should not be maintained for more than 10 minutes. Additionally, avoid total doses >500 μg/kg when using a continuous infusion >2 μg/kg/min (cyanide is produced faster than endogenous mechanisms can handle). • Cyanide toxicity may be more likely if a patient has hepatic dysfunction; thus consider reducing above-mentioned dosages. Thiocyanate toxicity may be more likely if there is renal dysfunction.

DIAGNOSIS • Patients can present with nonspecific signs and symptoms; furthermore there is no quick blood cyanide test to confirm toxicity. • Hypoxia, elevated lactic acid levels, and metabolic acidosis are considered to be the hallmarks of cyanide poisoning. • Perioperatively, anesthesia providers should maintain a high index of suspicion, presumptive diagnosis, and rule out cyanide toxicity in patients exposed to fire smoke, especially when the mouth and nares are tinged with soot (in addition to carbon monoxide poisoning). Additionally, patients on nitrovasodilators may also present with clinical symptoms and should be ruled out if appropriate • Central nervous system: Headache, confusion, dizziness, flushing, vertigo, seizures, and coma. At non-fatal levels, patients report the smell of almonds and feeling apprehensive. Survivors of cyanide toxicity may develop Parkinsonism due to damage to the basal ganglia. • Cardiac: Initial tachycardia and hypertension (sympathetic response to metabolic acidosis), followed by bradycardia and hypotension, AV block, and cardiovascular collapse. • Respiratory: An early sign is hyperventilation, which can increase the absorbed dose. This is followed by bradypnea, pulmonary edema, absence of cyanosis (due to increased mixed venous oxygen saturation), apnea, and respiratory arrest • GI: Vomiting, abdominal pain • Renal and hepatic failure • Dermatologic: Flushing and cherry red color of skin are late findings. • Chronic cyanide exposure can result in headache, Leber’s neuropathy, and tobacco amblyopia. Bright red retinal veins may be noticed due to elevated venous oxygen concentration

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Blood cyanide concentration. Laboratory measurement provides definitive diagnosis. Because results are not immediate or “on-the-spot,” they cannot aid in initial management. However, samples should be sent as soon as possible due to cyanide’s rapid metabolism and instability in blood samples. Toxicity threshold ranges from 0.5 to 1 mg/L, and the lethal threshold ranges from 2.5 to 3 mg/L • Arterial blood gas reveals a severe metabolic acidosis (low pH and low sodium bicarbonate) due to anaerobic metabolism with lactic acid production – PaO2 is high (represents cell’s inability to extract and utilize arterial oxygen, despite cell hypoxia). – Alveolar–arterial (A–a) gradient <10 mm Hg. The A–a gradient is reduced due to the highly oxygenated venous blood that results in higher arterial oxygen levels. • Lactate is increased in arterial and venous samples due to anaerobic respiration and can be additionally increased from other causes such as seizures, apnea, or administered catecholamines. • Anion gap: [Na +] – ([Cl−] + [HCO3−]) >15; gap is affected by changes in unmeasured ions, in this case lactic acid. Bicarbonate buffers and binds to lactic acid, thus decreasing its

concentration. • Mixed venous oxygen saturation. Venous blood has an abnormally high oxygen saturation that reflects tissue and cell inability to utilize oxygen (despite hypoxia).

Monitors

• Pulse oximetry: Normal, despite cellular hypoxia • EKG: Tachycardia followed by bradycardia, AV block • Noninvasive BP: Hypertension followed by hypotension. • Arterial line: Placement allows for frequent arterial blood gas measurements to follow therapy.

DIFFERENTIAL DIAGNOSIS

• Carbon monoxide poisoning • Tricyclic antidepressant poisoning • Isoniazid overdose • Organophosphate poisoning • Salicylate poisoning

TREATMENT • Cyanide poisoning is rapidly lethal; therefore, prompt recognition and early initiation of treatment are necessary to save live. • Decontamination. Prehospital care involves removing the victim from the source of cyanide to an area of fresh air and decontaminating the victim (removal of contaminated clothing, rinsing of skin if dermal exposure, gastric lavage and activated charcoal if ingested). If administering a nitrovasodilator (SNP), infusion should be immediately discontinued. • Supportive care. Administration of 100% oxygen can hasten respiratory excretion of cyanide and reactivate mitochondrial enzymes. Furthermore, carbon monoxide poisoning also requires high inspired oxygen and intubation (particularly with smoke inhalation injury due to the potential for airway swelling). • Benzodiazepines for seizure control and sodium bicarbonate can be administered to treat metabolic acidosis (pH <7.1). • Antidote treatment. The cyanide antidote kit (CAK) is the only currently available kit in the US. It is comprised of two forms of nitrites and sodium thiosulfate. Nitrite displaces oxygen (Amyl nitrite and Sodium nitrite) from hemoglobin to form methemoglobin that attracts cyanide to form cyanomethemoglobin. Sodium thiosulfate is the natural substrate for enzyme rhodanese and promotes conversion of cyanide to thiocyanate, an excretable and less toxic compound. Antidote kits have several side effects and are controversial; nitrite doses can result in dangerous levels of methemoglobinemia (reduces ability of blood to transport oxygen to the cells, blue skin and mucus membranes, vomiting, shock, and coma). Treatment is with 1% methylene blue 1–2 mg/kg. • Alternatively, sodium nitrate 300 mg IV over 2–4 minutes; sodium thiosulfate 12.5 g IV initial bolus and repeat 6.25 g IV in 30 minutes; or hydroxycobalmin.

REFERENCES

1. Desai S, Su M. Cyanide Poisoning: UpToDate Literature review 18.2: May 2010.

2. Barillo D. Diagnosis and treatment of cyanide toxicity. Journal of Burn Care and Research. 2009 January/February:148–152. 3. Baud FJ, Cyanide: Critical issues in diagnosis and treatment, human and experimental toxicology. (2007)26;191–201.

ADDITIONAL READING

• Koshchel MJ. Management of cyanide poisoned patient. J Emerg Nurs. 2006;32:S19–126. • Baker D. Chemical and Biological Warfare agents: The role of the Anesthesiologist; Miller’s Anesthesia, 7th ed. (Chapter 74), 2010. pp. 2345–2347.

See Also (Topic, Algorithm, Electronic Media Element) • Mixed venous oxygen • Metabolic acidosis

CODES ICD9 989.0 Toxic effect of hydrocyanic acid and cyanides ICD10 • T65.0X1A Toxic effect of cyanides, accidental (unintentional), init • T65.0X2A Toxic effect of cyanides, intentional self-harm, init encntr • T65.0X3A Toxic effect of cyanides, assault, initial encounter

CLINICAL PEARLS

• Anesthesia providers may encounter cyanide poisoning in the perioperative setting when patients present from fire smoke inhalation (in addition to carbon monoxide poisoning) or when utilizing nitrovasodilators (particularly SNP). • Cyanide binds to cytochrome c oxidase in the ETC, thereby preventing oxygen from accepting the donor electron. By hindering oxidative phosphorylation, it precludes aerobic metabolism, and the body resorts to anaerobic respiration with lactic acid production despite there being normal oxygen availability.

CYSTIC FIBROSIS Matthew Delph, MD Neal Campbell, MD

BASICS DESCRIPTION

• Cystic fibrosis (CF) is a progressive, autosomal recessive disease caused by impaired chloride ion transport with multiple organ system involvement. • The major source of morbidity and mortality is attributed to progressive obstructive pulmonary disease precipitated by chronic inflammation, infection, and destruction of airways. EPIDEMIOLOGY Incidence

• Caucasian births: 1:2,500 (1) • Hispanic births: 1:13,500 (1) • African American births: 1:15,100 (1) • New cases per year: 1,000 (2)

Prevalence

• Nearly 30,000 CF patients in the US (2) • Prevalence rapidly increasing due to increased survival rates and median age • 45% of patients are over the age of 18 (2)

Morbidity

• At least once yearly hospitalization: 35% • Most frequent cause of morbidity is acute exacerbation of pulmonary disease

Mortality

• Median survival is 38 years (2). • Respiratory disease accounts for 80–90% of morbidity and mortality (2)

ETIOLOGY/RISK FACTORS

• Autosomal recessive disorder • More common in Caucasians; it is the most common lethal inherited disease in Caucasians • Presence of meconium ileus, tobacco use, and female gender are associated with a more rapidly progressing disease course

PATHOPHYSIOLOGY

• Mutation of the Cystic Fibrosis Transmembrane Regulator (CFTR) gene on Chromosome 7 can result in CF. Defects result in abnormal chloride channel proteins, and impaired cAMP-

regulated chloride transport across epithelial cells. Thousands of different mutations exist; however, 75% of cases are due to deletion of phenylalanine (Δ 508) (2). • Mutations lead to decreased chloride secretion and increased absorption of cations, such as sodium, and water back into the cell. Although there are multiple theories, there is no consensus on the pathophysiology of clinical symptoms. • Mutations result in abnormally thick and sticky mucus that can build up in the exocrine glands of the lungs, pancreas, hepatic, and GI tract. See section “Concomitant Organ Dysfunction.”

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperatively, assess and treat concomitant organ system dysfunction. The pulmonary system requires careful preoperative evaluation; optimization may involve the use of bronchodilators, incentive spirometry, and postural drainage. • Intraoperatively, limit airway manipulation, humidify the airway, adequately hydrate, and adjust ventilator settings in order to increase alveolar recruitment. Avoid atelectasis and other parameters that may exacerbate obstructive lung disease. • Postoperatively, ensure adequate reversal of neuromuscular blocking drugs (NMBDs) and avoid prolonged post-op intubation if possible, as it increases morbidity and mortality. • Regional or neuraxial techniques should be considered to provide pain relief while limiting opioid use due to their depressive effect on the respiratory system.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Presence of cough • Quality and quantity of mucous • Dyspnea, paroxysmal nocturnal dyspnea (PND), orthopnea

History

• Age at diagnosis • Progression and severity of disease, affected organ systems, pulmonary functional status • Date and severity of last exacerbation or hospitalization • History of smoking • History of obstructive sleep apnea

Signs/Physical Exam

• Airway exam, neck, TMJ mobility • Work of breathing, use of accessory muscles • Wheezing, crackles, decreased breath sounds • Signs of chronic hypoxia (digital clubbing) • Hepatojugular reflex, peripheral edema • Stigmata of liver disease

TREATMENT HISTORY • Oxygen therapy

• CPAP/BIPAP use • Chest physiotherapy • Lung transplantation

MEDICATIONS

• Steroids • B-agonists and other bronchodilators • Recombinant DNAse (cleaves mucous) • Theophylline • Antibiotics • Insulin or oral hypoglycemic • Pancreatic enzyme replacement

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• The 1996 Cystic Fibrosis Foundation developed criteria for diagnosis: – Presence of 1 or more clinical features, family history of CF in a sibling, or positive newborn screening test and abnormal sweat chloride test, nasal potential difference, or identification of a known CF mutation (3)[C]. – The sweat-chloride test is the gold standard; values >60 mEq/L are considered positive. • Preoperative studies – CBC/chemistry panel – Coagulation studies: PT, PTT, INR – LFTs may reveal posthepatic obstruction due to increased bile viscosity. – Baseline ABG – Chest x-ray (CXR): Hyperinflation, pneumothorax, peribronchial thickening – CT chest: Bronchiectasis, apical blebs – Pulmonary function tests (PFTs): Obstructive pattern with a decrease in FEV1 and peak expiratory flow, and increase in residual volume (RV).

CONCOMITANT ORGAN DYSFUNCTION

• Airway manifestations include an increased incidence of nasal polyps and chronic sinusitis. Nasal mucosa hypertrophy and hyperplasia may also be present. • Pulmonary disease manifests as airway obstruction, bacterial colonization, atelectasis, and hypoxia. It results from an increase in goblet cells and mucus production. PFTs demonstrate an obstructive pattern with decreased FEV1, vital capacity, and peak flows as well as

increased RV. – Although there are multiple hypotheses, there is no consensus on why bacterial colonization occurs, most commonly with organisms Pseudomonas aeruginosa, Haemophilus influenza, and Staphylococcus aureus. – Chronic disease leads to pulmonary hypertension and cor pulmonale; patients often require lung transplantation. • Pancreatic disease manifests as exocrine and endocrine dysfunction secondary to impaired bicarbonate secretion. The retention of digestive enzymes can cause autodigestion with an

increased risk for pancreatitis. – Pancreatic exocrine dysfunction describes protein and fat malabsorption, failure to thrive, deficiency of fat soluble vitamins (A, D, E, K) – Pancreatic endocrine dysfunction describes pancreatic beta-cell destruction and can often lead to diabetes mellitus (DM). Approximately 30% of patients develop DM by age 30 (2). • Hepatobiliary disease manifests as cholelithiasis and cholecystitis from pancreatic duct stenosis as well as cirrhosis, and hepatocellular carcinoma. Cirrhosis is the second most common cause of death and is present in 10% of patients; abnormal LFTs are seen in 33% of patients; fatty infiltration is present in 70% of patients. • GI tract disease presents as meconium ileus; thickened feces can result in distal intestinal obstruction syndrome. There is a high incidence of GERD. • Musculoskeletal abnormalities present as low bone mineral density, kyphosis, scoliosis, and rib fractures. This results from a combination of decreased vitamin D absorption, lack of exercise, chronic steroid therapy, and low androgen levels. • Coagulation abnormalities can manifest from pancreatic dysfunction (impaired absorption of vitamin K) and hepatic disease. • (In)Fertility. The majority of males are infertile due to the absence of a vas deferens. Females have thick cervical mucus that often prevents pregnancy.

Pregnancy Considerations

• Increased incidence of preterm labor. • Gravid patients are more susceptible to right heart failure.

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Acute pulmonary exacerbation • LFTs greater than 1.5 times normal should be investigated (2)[C]. • Coagulopathies should be corrected

CLASSIFICATIONS See ICD9 section

TREATMENT PRE-HOSPITAL Premedications

• Bronchodilators should be considered preoperatively when signs of bronchoconstriction or wheezing are present (2)[C]. • Mucolytics (DNAses) can be used to improve airway clearance. • Anticholinergics may further dry mucous and secretions; consider avoiding. • Acid reducers (H2 blockers) should be considered in patients with poorly controlled GERD (4)[C].

Special Concerns for Informed Consent

The potential for postoperative respiratory failure and the need for ventilator support

INTRAOPERATIVE CARE Choice of Anesthesia

Consider regional or neuraxial anesthesia to limit airway manipulation or as an adjunct for postoperative pain control (4)[C].

Monitors

• Consider arterial line for frequent ABGs or blood glucose levels in diabetics • TEE in patients with right heart failure

Induction/Airway Management

• Sedation should be considered whenever possible to avoid airway manipulation and mechanical ventilation. • For general anesthesia, IV or inhalational induction may be used. Patients may exhibit a prolonged inhalation induction secondary to increases in RV. If an inhalation induction is chosen, consider sevoflurane (favorable blood:gas solubility compared to isoflurane and less irritating to the airways than desflurane). Ketamine can increase secretions and should be avoided (4). • Laryngeal mask airways have the potential benefit of reduced airway reactivity; drawbacks include the inability to protect against GERD or airway secretions, provide significant positive pressure ventilation, or ventilate and oxygenate in the event of laryngospasm. • Avoid nasotracheal intubation (and nasal airways) due to nasal mucosa hyperplasia. • Large single lumen tubes are preferred to allow for lavage or bronchoscopy. • Neuromuscular blockade may lead to airway obstruction. • A RSI may be considered in patients with uncontrolled GERD.

Maintenance

• A balanced technique with volatile or total IV anesthesia. Volatile agents have the potential benefit of providing bronchodilation. • Humidifying inhaled gases can reduce thickening of secretions. • Frequent intraoperative suctioning should be considered. • Treat bronchospasm with bronchodilators, deepening of the anesthetic (volatile agent), epinephrine subcutaneous or IV, terbutaline, or theophylline as appropriate. • Avoid nitrous oxide due to an increased risk of pneumothorax (4)[C] • Opioids should be limited due to respiratory depression. Attempt to treat postoperative pain with NSAIDS and/or regional/neuraxial blocks (2)[C].

Extubation/Emergence

• Ensure adequate reversal of NMBDs • Endotracheal suctioning, alveolar recruitment measures should be performed; consider chest physiotherapy (2)[C]. • Position the patient with the head of the bed elevated 30–40° for extubation (4)[C]. • Early extubation improves morbidity and mortality (2)[C].

POSTOPERATIVE CARE

BED ACUITY

• Patients with mild disease and less complex procedures may be discharged home after being monitored in the PACU (2)[C]. • Patients with more severe pulmonary disease or those undergoing more invasive procedures should be monitored either in an intensive care unit (ICU) or monitored bed (4)[C].

MEDICATIONS/LAB STUDIES/CONSULTS

• Chest physiotherapy, CXR • Consider pulmonary consultation if postoperative mechanical ventilation is required.

COMPLICATIONS

• Respiratory depression, airway obstruction, atelectasis, pneumonia, pneumothorax • Postoperative jaundice

REFERENCES 1.

Cystic Fibrosis Clinical Validity. Sept 10 2007. http://www.lungusa.org/assets/documents/ALA_LDD08_CF_FINAL.PDF. Accessed on Jan 26, 2011. 2. Huffmyer JL. Perioperative management of the adult with cystic fibrosis. Anesth Analg. 2009;109(6):1949–1961. 3. Farrell PM. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic fibrosis foundation consensus report. J Pediatr. 2009;153(2):S4–S14. 4. Della Rocca G. Anaesthesia in patients with cystic fibrosis. Curr Opin Anaesthesiol. 2002;15(1):95–101.

ADDITIONAL READING

• Davis PB. Cystic fibrosis since 1938. Am J Respir Crit Care Med. 2005;173:475–482.

See Also (Topic, Algorithm, Electronic Media Element) • Ciliary function • Chloride • Cor pulmonale

CODES ICD9 • 277.00 Cystic fibrosis without mention of meconium ileus • 277.01 Cystic fibrosis with meconium ileus • 277.02 Cystic fibrosis with pulmonary manifestations ICD10 • E84.0 Cystic fibrosis with pulmonary manifestations

• E84.9 Cystic fibrosis, unspecified • E84.11 Meconium ileus in cystic fibrosis

CLINICAL PEARLS

• Optimize preoperative pulmonary function; intraoperative and postoperative management should aim at clearing secretions and managing as an “obstructive pulmonary disease” patient. Extubation is desired but must be balanced against risks. • Assess and treat CF-associated comorbidities.

CYSTOSCOPY Jonathan Anson, MD

BASICS DESCRIPTION General

• A cystoscopy is performed to visualize and examine the inner surface of the urethra and bladder; it is an endoscopic procedure. • The cystoscope is either flexible or rigid and is inserted into the urethra. The distal end has either a lens or fiberoptic apparatus to allow visualization via a proximal eyepiece or monitor, respectively. – To enhance visualization, sterile fluid is used to distend and stretch the bladder. – The cystoscope has extra channels that allow for instruments to be inserted in order to perform biopsies, stent placement, dilation, laser procedures, stone removal, or intravesical administration of medications (e.g., Bacillus-Calmette-Guérin (BCG): A live, attenuated strain of Mycobacterium bovis as adjuvant treatment for nonmuscle invasive bladder cancer). • Modifications/enhancements of this endoscopic procedure include transurethral resection of bladder tumor (TURBT) and transurethral resection of the prostate (TURP). A resectoscope is utilized to remove the tissue. • Indications include frequent urinary tract infections (UTIs), hematuria, unusual cells seen in urine samples, chronic pelvic pain, cystitis, dysuria, blockage from the prostate, stones, or abnormal growth/tumor/polyps. • A ureteroscope is a longer, thinner instrument that can be used to visualize and examine the ureters and upper urinary tract structures. Position

• Lithotomy • Often requires the Trendelenburg position

Incision

Natural orifice procedure via the urethra Approximate Time

5 minutes to 1 hour EBL Expected Minimal

Hospital Stay

Pathology dependent. Many procedures are performed on an outpatient basis.

Special Equipment for Surgery • Cystoscope • Ureteroscope • Resectoscope

EPIDEMIOLOGY Incidence

Approximately 67,000 new cases of bladder cancer per year. Prevalence

Bladder cancer is three times more common in males than females; more common in patients >55 years old; and twice as common in Caucasians as African Americans. Morbidity

• Pain • Urinary tract infection • Urinary tract obstruction • Bladder, urethral, or urethra perforation or injury

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The lithotomy and Trendelenburg positioning can result in decreased functional residual capacity (FRC) and decreased pulmonary compliance. • Akinesis should be maintained during the procedure to reduce the risk of bladder or ureteral perforation. Leg movement should be prevented at the end of the procedure and until the patient is out of the lithotomy position to avoid hip injury. • Patients are often elderly and with multiple comorbidities. Geriatric considerations and adjustment of drug dosages are often necessary. • Autonomic hyperreflexia can occur in patients with spinal cord injury; thus, neuraxial or general anesthesia is needed to prevent this occurrence with bladder distension. • If laser therapy is used, protective goggles for the patient and operating room personnel should be utilized.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Often asymptomatic • May present with hematuria • Abdominal pain, flank pain • Urinary frequency, urgency, or dysuria • Anuria if there is urinary tract obstruction

History

• Hematuria • Calculi

• Bladder tumor/cancer • UTI • Urinary tract obstruction • Hydronephrosis

Signs/Physical Exam

• Tachycardia or fever may suggest an infectious process • Cardiopulmonary exam

MEDICATIONS

• Alpha blockers for benign prostatic hypertrophy (BPH) can compound hypotensive effects of anesthetics • 5-alpha-reductase inhibitors for BPH • Antimuscarinics for overactive bladder • Drugs for erectile dysfunction are nitric oxide derivatives and can compound hypotensive effects of anesthetics • Anticoagulants and blood thinner for coexisting conditions may contraindicate neuraxial techniques. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Metabolic panel if acute kidney injury is suspected • CBC and coagulation factors if hematuria • Urinalysis and urine culture, if UTI • EKG and chest x-ray as per standard criteria • Renal ultrasound for urinary tract obstruction and hydronephrosis • Abdominal plain film or CT scan may show calculi

CONCOMITANT ORGAN DYSFUNCTION

• Acute kidney injury, especially in the face of urinary tract obstruction (postrenal failure) • Chronic kidney disease • Patients with prosthetic heart valves or atrial fibrillation may develop hematuria from heparin or warfarin. • Urosepsis in patients with UTI or pyelonephritis.

Pregnancy Considerations

• The incidence of calculi is the same in pregnancy as the general population. When it does occur, it is seen more commonly in the 2nd and 3rd trimester. Stones typically pass spontaneously but cystoscopy with stent placement may be necessary if the patient is septic or has a urinary tract obstruction. The complication rate of ureteroscopic stone removal is no different in pregnant patients than in nonpregnant patients (1)[A]. • A neuraxial or general technique can be utilized. Spinal and epidural blocks can decrease the amount of medication administered and should be considered in patients who are early in pregnancy or have a potentially difficult airway. • Goals should be to avoid teratogenic drugs, maintain oxygenation and baseline

hemodynamics, and provide left uterine displacement if possible. • Consult an obstetrician for guidance on preoperative, intraoperative, and postoperative fetal monitoring.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis as appropriate; use cautiously in elderly patients. • Opioids as appropriate

Special Concerns for Informed Consent

Patients undergoing monitored anesthesia care or a regional technique plus MAC should still be consented for general anesthesia as a backup. Antibiotics/Common Organisms

• First line: Fluoroquinolone within 1 hour of the procedure • Second line: Trimethoprim–sulfamethoxazole, or gentamicin with ampicillin • Escherichia coli is most common organism

INTRAOPERATIVE CARE Choice of Anesthesia

• Local anesthesia is often used for flexible diagnostic cystoscopy. • Monitored anesthesia care should be considered for diagnostic flexible cystoscopy in patients unable to tolerate local anesthesia. • Neuraxial anesthesia with a T10 level is adequate for most urologic procedures. However, it does not reliably block the obturator nerve. An awake patient is the best monitor for mental status changes in TURP syndrome. • Regional anesthesia. An obturator nerve block may be considered in conjunction with neuraxial techniques if inferolateral bladder wall resection is anticipated. It prevents patient movement if the nerve is stimulated and decreases the risk of bladder perforation (2)[A]. • General anesthesia is commonly used.

Monitors

• Standard ASA monitors • Invasive monitoring is dictated by the patient’s comorbidities

Induction/Airway Management

• General anesthesia with a laryngeal mask airway (LMA) or endotracheal tube (ETT). • LMA can be used if the patient is NPO, not at risk for aspiration, and has an “adequate" FRC. Supraglottic devices may decrease the incidence of airway reactivity in patients with asthma or chronic obstructive pulmonary disease (COPD). Muscle relaxation for the procedure may still be utilized. • ETT should be used if the patient is not NPO, possesses risk factors for aspiration, or if the

lithotomy and Trendelenburg positions may hinder spontaneous ventilation (e.g., truncal obesity, decreased pulmonary compliance). • In patients with renal failure or hyperkalemia, succinylcholine may be contraindicated. If a rapid sequence induction is indicated, consider rocuronium (drawback = duration may be prolonged) or cisatracurium (drawback = longer time to onset).

Maintenance

• Balanced anesthetic with volatile or IV medications. • Surgical irrigating fluids may be absorbed in some cases. TURP procedures pose the highest risk due to open prostatic venous sinuses; thus irrigating time should be kept as short as possible. • Hemodynamics should be maintained close to baseline values, particularly in patients with end-organ damage. • Hypothermia may occur due to cold irrigating fluids. Normothermia can be maintained with increased ambient room temperature, upper body forced air warming blanket, or warm IV fluids. • Narcotics. In patients who are spontaneously breathing with an LMA, titrate to respiratory rate. • Duration of action of nondepolarizing muscle relaxants may be prolonged if gentamicin is given or the patient is hypothermic. • Radiation safety precautions should be implemented if fluoroscopy is used. • Laser protective goggles should be implemented for the patient and OR staff if laser therapy is utilized.

Extubation/Emergence

• Antiemetic prior to emergence • Ensure complete akinesis until legs are out of lithotomy. • Awake extubation after reversal of muscle relaxation and when routine respiratory parameters are met.

POSTOPERATIVE CARE BED ACUITY

• PACU for immediate postoperative care • Nontelemetry floor bed is appropriate for most inpatients. • Telemetry unit if the patient has a history of arrhythmia or severe cardiovascular disease. • Intensive care unit (ICU) admission for TURP syndrome.

ANALGESIA

• Some patients feel more comfortable postoperatively (e.g., after stone removal) • IV opioids with transition to PO opioids

COMPLICATIONS

• Monitor urine output as clots may form in the urinary catheter. • Abdominal pain with referred shoulder pain warrants workup for bladder perforation.

• UTI • Stent migration • TURP syndrome • Ureteral perforation • Autonomic hyperreflexia • Hematuria/clots in Foley catheter • Acute kidney injury • Sepsis and cystitis from BCG; considerably higher incidence in patients >70 years old, especially with repeated doses (3)[B].

PROGNOSIS

Urinary obstruction may lead to irreversible kidney injury. Reversibility is dependent on duration and severity of obstruction.

REFERENCES

1. Khorrami MH, Javid A, Saryazdi H, et al. Transvesical blockade of the obturator nerve to prevent adductor contraction in transurethral bladder surgery. J Endourol. 2010;24(10):1651–1654. 2. Semins MJ, Trock BJ, Matlaga BR. The safety or ureteroscopy during pregnancy: A systematic review and meta-analysis. J Urol. 2009;181:139–143. 3. Heiner JG, Terris MK. Effect of advanced age on the development of complications from intravesical bacillus Calmette-Guérin therapy. Urol Oncol. 2008;(26)2:137–140.

ADDITIONAL READING

• http://www.auanet.org (American Urological Association). See clinical guidelines tab.

See Also (Topic, Algorithm, Electronic Media Element) • Acute renal failure • Postrenal failure • TURP syndrome • Radiation safety

CLINICAL PEARLS

• Patients are often elderly and have numerous comorbidities, requiring careful preoperative evaluation. • Obturator nerve block is an easy, effective means to avoid obturator stimulation during a TURBT. • Duration of action of nondepolarizing muscle relaxants may be extended with administration of gentamicin. • There are no studies showing improved renal outcome with general versus neuraxial anesthesia. • Neuraxial anesthesia allows early recognition of mental status change in TURP syndrome.

D-DIMER

Mark R. Bombulie, BS

BASICS DESCRIPTION

• D-dimer is an antigen that is produced from plasmin-mediated degradation of fibrin-rich thrombi. • D-dimer assays are a useful tool for the: – Exclusion of deep venous thrombosis (DVT) and pulmonary embolism (PE) – Diagnosis of disseminated intravascular coagulation (DIC) (1) • The D-dimer measurement is an adjunct test and should never be used in isolation for diagnosis or exclusion (2). PHYSIOLOGY PRINCIPLES

• In the final steps of the coagulation pathway, thrombin cleaves fibrinogen to produce fibrin monomers. These fibrin monomers polymerize with one another forming protofibrils, thus allowing factor XIII to bind. • Thrombin also serves to activate factor XIII bound to fibrin polymers (forming factor XIIIa). • Factor XIIIa catalyzes the formation of covalent bonds between the D-domains (the segment of the fibrin protein containing the D-dimer antigen sequence) in adjacent protofibrils of polymerized fibrin. • During fibrinolysis, activated plasmin degrades the cross-linked fibrin, which releases fibrin degradation products and exposes the D-dimer antigen, which is typically not present in the body except when the coagulation system has been activated. • The D-dimer assay – The required sample is venous blood in a light blue tube (the same tube used for PT/PTT). The tube must be completely filled. – Quantitative values are performed in the laboratory with plasma and have a sensitivity of 95% and specificity of 50%. Quantitative tests rely on either enzyme-linked immunosorbent assays (ELISA) or enzyme-linked fluorescent assays (ELFA) to detect the amount of D-dimer present. – Qualitative values can be obtained at the bedside with whole blood and have lower sensitivities (85%) but slightly higher specificities (70%) than quantitative values. Whole blood is mixed with a reagent (a D-dimer monoclonal antibody that is joined to a monoclonal antibody capable of binding to the surface of a red blood cell). When D-dimer is present above a threshold value, agglutination occurs (the conjoined antibodies cause D-dimer and RBCs to clump together). This technique has the advantage of yielding results quickly without advanced laboratory equipment, but it is unable to detect low levels of D-dimer (3). – Increased values suggest increased thrombus formation or breakdown in the body. DISEASE/PATHOPHYSIOLOGY

• DVTs can embolize and travel through the right heart and into the pulmonary vasculature, causing a mechanical obstruction to blood flow (pulmonary embolism) and a secondary immune-inflammatory response. Risk factors include: – Previous history – Hereditary causes: Antithrombin III deficiency Protein C and S deficiencies Factor V Leiden Prothrombin gene mutations – Acquired causes: Reduced mobility Cancer Pregnancy/postpartum Nephrotic syndrome Trauma Spinal cord injury – Medications: Hormone replacement therapy Oral contraceptives Chemotherapy Antipsychotics – Surgical factors: Major surgery Hip or leg fracture Hip or knee replacement General anesthesia compared to epidural/spinal anesthesia (4) • Dead space: Pulmonary emboli result in an increase in alveolar dead space with an associated right-to-left shunt and V/Q mismatch. Blood shunted away from the blocked pulmonary arteries can cause edema, loss of surfactant, and alveolar hemorrhage in the overly perfused lung segments (5). Acute blockage can cause right heart strain or acute cor pulmonale. • DIC causes include infection, malignancy, obstetric disorders, shock, liver disease, extracorporeal circulation, intravascular hemolysis; it is the end result of several disease processes and has a high mortality rate. DIC is characterized by continuous thrombin generation and fibrin formation in the microvasculature which ultimately deplete coagulation factors and their inhibitors, leading to bleeding and/or thrombotic state. The subsequent breakdown of formed fibrin leads to the elevated D-dimer seen in this condition.

PERIOPERATIVE RELEVANCE

• Pulmonary embolism – Perioperative PE has an incidence of 1.6% in patients undergoing general surgery. The incidence in patients undergoing orthopedic procedures, especially hip procedures, has been reported as high as 30%. – ELISA D-dimer assays have a sensitivity of 95% and specificity of 50% and are therefore helpful in ruling out perioperative PE in patients with low clinical suspicion. In patients

with high clinical suspicion, ordering a D-dimer does not change management and should not delay treatment. – Values >500 ng/mL are considered positive. – False positives may be seen in other conditions unrelated to PE, including infection, cancer, trauma, cardiac disease, rheumatoid arthritis, hyperbilirubinemia, hepatic disease, in the elderly, the surgical procedure itself, hemolysis, or other inflammatory states. • Disseminated intravascular coagulation – In pregnant women with microangiopathic hemolytic anemia, elevated liver enzymes, and low platelets (HELLP) syndrome, 15–38% can progress to DIC. – DIC can be diagnosed intraoperatively with thrombocytopenia, elevated PT, aPTT, and Ddimer (6). – D-dimer levels >200 ng/mL are considered elevated. Levels correlate with the severity of the disease and can be monitored to assess the effectiveness of therapy.

REFERENCES

1. Thachil A, Fitzmaurice DA, Toh CH. Appropriate use of d-dimer in hospital patients. Am J Med. 2010;123:17–19. 2. Frost SD, Brotman DJ, Michota FA. Rational use of D-dimer measurement to exclude acute venous thromboembolic disease. Mayo Clin Proc. 2003;78:1385–1391. 3. Adam SS, Key NS, Greenburg CS. D-dimer antigen: Current concepts and future prospects. Blood. 2008;113:2878–2887. 4. Martlew VJ. Peri-operative management of patients with coagulation disorders. Br J Anaesth. 2000;85(3):446–455. 5. Desciak MC, Martin DE. Perioperative pulmonary embolism: Diagnosis and anesthetic management. J Clin Anesth. 2011;23:153–165. 6. Garg R, Nath MP, Bhalla AP, et al. Disseminated intravascular coagulation complicating HELLP syndrome: Perioperative management. BMJ Case Rep. 2009. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary embolism

CLINICAL PEARLS

• A positive D-dimer may indicate an increased level of fibrin degradation products that can result from increased thrombus formation or breakdown in the body. It cannot identify the location or the cause. • D-dimer assay can be used to rule out PE in patients with low clinical suspicion. • D-dimer levels can be followed to monitor the effectiveness of treatment in patients with DIC. • D-dimer assay should never be used in isolation.

DEAD SPACE

Siamak Rahman, MD

BASICS DESCRIPTION

• Dead space (VD) describes the lung areas that are ventilated but not perfused. Perioperatively it includes: – Physiologic dead space: Anatomic and alveolar – Apparatus dead space: Most concerning for neonates • Increases in the dead space to alveolar ventilation (VD:VA) ratio result in the retention of carbon dioxide. Thus, any cause of increased VD would require increases in ventilatory support/parameters in order to maintain normocarbia. PHYSIOLOGY PRINCIPLES

• Physiologic dead space (VDtotal) does not participate in carbon dioxide or oxygen exchange.

It is composed of 2 different components of lung volume: – Anatomic (VDanatomic): Upper airway structures that do not contribute to gas exchange;

includes air in the nose, pharynx, larynx, trachea, and larger airways. This volume does not reach the alveolar level, will not participate in gas exchange, and is thus “wasted.” It is ∼1/3rd of the tidal volume, or 2 mL/kg. – Alveolar (VDalveolar): Ventilated alveoli receiving minimal blood flow; includes zone 1 and nondependent lung areas. – VDtotal = VDanatomic + VDalveolar

• Apparatus, mechanical, or equipment dead space: Perioperatively, the anesthetic delivery system and monitors can add dead space; it can become significant with pediatric patients. As the volume increases, less fresh gas moves into the patient’s alveoli to participate in gas exchange. This also applies to intubated and ventilated patients in the ICU. – Endotracheal tube or laryngeal mask airway; dead space volume exists in the portion that extends beyond the patient’s incisors (can be decreased by cutting the ETT). Of note, however, intubation results in ∼1/2 of the anatomical dead space being bypassed (volume of dead space in nasopharynx and mouth). – Airway adaptors: Straight and elbow can add ∼2 mL of dead space – End-tidal CO2 monitors can add ∼8 mL of dead space. The closer the ETCO2 monitor is positioned to the ETT, the less is the amount of dead space. – Extenders such as corrugated devices – Face masks – Humidification management exchangers (HME) – Y piece: Adults ∼8 mL; pediatric ∼4 mL – Malfunctioning one-way valves – Bain circuit with a cracked or broken center portion

– Exhausted soda lime: Unique in that it normally clears CO2 within the circuit; thus, when

it is exhausted, it no longer participates in “ventilation.” • Bohr equation was presented in the beginning of the 20th century. The dead space fraction could be determined by measuring the arterial CO2 (PaCO2) via blood gas measurements and the mean expired CO2 (PeCO2). The end-tidal CO2 (ETCO2) is often substituted for the

mean expired CO2 (1).

• Fowler’s method—a test for measuring the dead space via nitrogen washout during one or multiple breaths. The patient takes a breath of 100% oxygen and exhales through a one-way valve measuring nitrogen content and volume. It is not commonly used or available perioperatively. • Breathing efficiency—defined as the volume of fresh gas reaching the alveoli (alveolar tidal volume) divided by the total volume of the gas inhaled per breath (total tidal volume). In normal healthy adults who are breathing spontaneously at rest, it is normally between 60% and 70% (this means that ∼30–40% of inhaled fresh gas does not reach the alveoli).

DISEASE/PATHOPHYSIOLOGY

• Alveolar dead space can be increased in pathological states. Non-perfused, but ventilated, alveoli are defined as lung units with a V/Q ratio of infinity. They include: – Pulmonary embolus – Low cardiac output – Increased alveolar pressure from mechanical ventilation or positive end expiratory pressure (PEEP) – Chronic obstructive pulmonary disease • “Shunt dead space” is an erroneous description of right-to-left lung shunt that brings the higher CO2 concentration in venous blood to the arterial side, thereby producing an arterialto-end-tidal CO2 difference. However, the influence of shunt on dead space is fairly small

when shunt values are low; they become significant when the shunt has reached 50%. • Hypercarbia can potentially have profound effects: – Directly increases cerebral blood flow and intracranial pressure – Increases pulmonary arterial pressure • Sympathetic activation can result in tachycardia, hypertension, or arrhythmias.

PERIOPERATIVE RELEVANCE

• Assessing and measuring VD/VA or dead space will give insight into the matching of ventilation and perfusion and is useful in: – Evaluating mortality risk in acute respiratory distress syndrome; increases in VD/VA correlate with the severity of lung injury. – Indicating lung recruitment versus overdistention when PEEP is added or increased to

improve oxygenation – Predicting successful extubation in pediatric and adult patients – Diagnosing and assessing the severity of pulmonary embolism. The alveolar dead space can increase to excessive amounts (80–90% of the tidal volume in recurrent pulmonary embolism). – Providing valuable information on the ventilatory support of the critically ill by providing information regarding changes in volume of alveolar dead space (2) • Breathing pattern: Rapid, shallow breathing, as may be seen from abdominal or thoracic incisional pain, can result in small tidal volumes, and an increased fraction of dead space ventilation (may reach >50%). Continuous epidural anesthesia in the postoperative period may decrease this (as well as atelectasis); the benefits may be pronounced in pulmonary cripples with low reserves. • Pulmonary embolism: Fat, venous, air, or clot embolic phenomenon may result intraoperatively with sudden pulmonary vascular occlusion. The resultant V/Q mismatch can produce a sudden increase in alveolar dead space and decreased ETCO2 readings (PaCO2 will increase).

• Neonates and infants: Apparatus dead space is more concerning in this patient population. A 5 kg neonate has a dead space of ∼10 mL. The addition of apparatus can add several milliliters causing the VD/VA ratio to increase significantly. • Tracheostomy: Reduces dead space ventilation and improves the efficiency of ventilation. Studies have shown that tracheostomy can reduce VD by 70 mL and reduce the work of breathing by over 30% (3)[C]. • Compensatory breathing techniques: During respiratory distress in the spontaneously ventilating, non-intubated patient, an instinctive unidirectional breathing pattern may develop to avoid rebreathing air in the nose with a high CO2. This consists of inhaling via the nose, and exhaling through the mouth.

EQUATIONS

• VDtotal = VDanatomic + VDalveolar

• Bohr equation was presented in the beginning of the 20th century:

– Where PeCO2 is the partial pressure of CO2 in mixed expired gas and is equal to the mean expired CO2 or end-tidal CO2

– PaCO2 is equal to arterial CO2. GRAPHS/FIGURES

FIGURE 1. Total dead space is equal to the anatomic dead space plus the alveolar dead space.

REFERENCES

1. Blanch L, Romero PV, Lucangelo U. Volumetric capnography in the mechanically ventilated patient. Minerva Anestesiol. 2006;72(6):577–585. 2. Hedenstierna G, Sandhagen B. Assessing dead space: A meaningful variable? Minerva Anestesiol. 2006;72(6):521–528. 3. Chadda K, Louis B, Benaissa L, et al. Physiological effects of decannulation in tracheostomized patients. Intens Care Med. 2002;28:1761–1767. See Also (Topic, Algorithm, Electronic Media Element) • ETCO2

• Respiratory acidosis • Venous air embolism • Fat embolism • Tracheostomy

CLINICAL PEARLS

• Patients with normal lung function have narrow gradients between their ETCO2 and arterial CO2 concentration (PaCO2) of 0–5 mm Hg. Air in the physiologic dead space accounts for

this normal gradient. In diseased lungs, the gradient will increase due to ventilation– perfusion mismatch. • The increase in physiologic dead space and worsening of ventilation–perfusion matching that occurs with venous air embolism produce a sudden fall in ETCO2, which, although sensitive, is a nonspecific sign of venous air emboli and also occurs with other type of emboli, massive blood loss, circulatory arrest, or disconnection from the anesthesia circuit.

DEEP EXTUBATION (ANESTHETIZED EXTUBATION) Katy E. French-Bloom, MD

BASICS DESCRIPTION

Deep extubation describes removal of the endotracheal tube (ETT) from the trachea while the patient is still anesthetized, or deeply anesthetized (1). It requires that the: • Muscle relaxation is fully reversed. • Patient is maintaining an acceptable respiratory rate and tidal volume for their size. • Patient does not respond to pharyngeal suctioning. • Provider must remain vigilant in their attention to airway maintenance until the patient is fully awake. • Removal of the ETT occurs during a positive pressure breath. ALERT This is a controversial technique. It is not considered mandatory in most postoperative settings. When conducting a deep extubation, be aware you are giving up a secure airway (1).

Geriatric Considerations

Can be advantageous in patients with certain comorbidities, including hypertension and chronic obstructive pulmonary disease (2) Pediatric Considerations

Can be advantageous for certain pediatric procedures. Remember that the cricoid cartilage is the narrowest part of the pediatric airway. Use cautiously in cases where laryngeal edema is common. Children can be symptomatic as their small airway size is more severely compromised by edema (3). pregnancy considerations

Contraindicated in this patient population as they are always considered full stomach and at a high risk for pulmonary aspiration (4) PHYSIOLOGY PRINCIPLES

• There are 4 stages of anesthetic depth: – Stage 1 (Analgesia): Characterized by slow, regular breathing with diaphragm and intercostal muscles, and the presence of lid reflex – Stage 2 (Delirium): Characterized by irregular and unpredictable ventilation, reflex dilation of the pupils, and intact lid reflex. The risk of clinically important reflex activity such as vomiting, laryngospasm, or arrhythmias increases – Stage 3 (Surgical anesthesia): This stage has 4 planes: Plane 1: Slight somatic relaxation, regular periodic breathing, active ocular muscles

Plane 2: Breathing changes, inhalation becomes briefer than exhalation, eyes become immobile Plane 3: Abdominal muscles relax, diaphragmatic breathing becomes very prominent, eyelid reflex is absent Plane 4: Intercostal muscles become completely pararlyzed, rib cage movement paradoxical, breathing irregular, pupils dilate. – Stage 4 (Respiratory paralysis): Muscles are flaccid, eyes wide and dilated

ANATOMY

• Pharynx: The pharyngeal airway extends from the posterior aspect of the nose down to the cricoid cartilage. • Larynx: Lies at the level of the cervical vertebrae 3–6; it is an organ of phonation and acts as a valve to protect the lower airways from contents of alimentary tract. • Epiglottis: A fibrous cartilage that is a part of the larynx. It has a mucous membrane covering that reflects as the glossoepiglottic fold onto the pharyngeal surface of the tongue. The epiglottis projects into the pharynx and overhangs the laryngeal inlet. It is not absolutely necessary for sealing off the airway during swallowing.

PERIOPERATIVE RELEVANCE

• Advantages of deep extubation (1,2,5,6): – Decreases stress response to extubation; less fluctuation in blood pressure/hypertension and heart rate/tachycardia – Decreases coughing and bucking on the ETT – Less incidence of desaturation – Less laryngotracheal trauma – Less breath-holding, bronchospasm • Disadvantages/complications of deep extubation (4): – Laryngospasm and/or bronchospasm can occur if the patient is extubated in between the awake and anesthetized states (Stage 2). – Loss of a secure airway – Aspiration – Negative pressure pulmonary edema – May require nasal/oral airway or laryngeal mask airway (LMA) after removal of ETT • Indications for deep extubation: – Specific surgeries including (6): Unclipped intracranial aneurysms Open globe eye surgery Intracranial aneurysm clipping (5) Tympanoplasty surgery Thyroid/parathyroid surgery Tonsillectomy/adenoidectomy (7,8) Removal of laryngeal papillomatosis (9) – Patients with specific comorbidities: Hypertension (2) Tachydysrhythmias

Reactive airway disease (4) • Contraindications to deep extubation (1): – Difficult mask ventilation – Difficult intubation – Increased risk of aspiration/full stomach – Surgery that may cause airway edema – Obesity – Diagnosis of obstructive sleep apnea (relative) – Neuromuscular disorders such as primary muscle diseases, demyelinating diseases, myasthenic syndromes, ion channel myotonias • Prior to a deep extubation (same for adult and pediatric patients) – Muscle relaxants must be fully reversed. – An adequate anesthetic depth must be maintained; eyes in midline, indicating at least a Stage 3 depth of anesthesia. – Patient should be breathing 100% oxygen. – Patient must be maintaining an acceptable respiratory rate and depth. – The posterior pharynx of the patient must be thoroughly suctioned; there should be no reaction by the patient to this. – Placement of a well-lubricated nasal trumpet may be considered in patients at risk for obstruction (e.g., large tongue). – The ETT is removed after a positive pressure breath has been given with the anesthesia reservoir bag to allow expulsion or secretions out of the glottis. • Immediately following deep extubation: – Oxygen should be administered to the patient in the form of a facemask for adults, and either a facemask or blow-by oxygen for pediatric patients. – Laryngospasm can occur especially when extubation is performed during Stage 2. Laryngospasm is the prolonged, intense glottis closure in response to direct glottis or supraglottic stimulation from inhaled agents, secretions, or foreign bodies. Patients usually produce sounds that range from high-pitched and squeaky to complete absence. Treatment of laryngospasm consists of recognizing this condition and then treating it appropriately; partial laryngospasm may be managed with 100% oxygen administration, CPAP, and jaw thrust whereas complete laryngospasm (or unremitting partial laryngospasm) requires propofol or muscle relaxation (most commonly succinylcholine). – Obstruction from the tongue or redundant tissue may be relieved with repositioning of the head, jaw thrust, insertion of an oral airway or nasal trumpet, or positive pressure ventilation with a facemask. • Recovery room care following deep extubation: – The “no-touch” technique for pediatric and adult patients involves not touching or manipulating the airway until the patient is fully awake. – Patients must be fully monitored for the duration of their stay in PACU.

REFERENCES

1. Daley MD, Norman PH, Coveler LA. Tracheal extubation of adult surgical patients while deeply anesthetized: A survey of U.S. anesthesiologists. J Clin Anesth. 1999;11(6):441–444.

2. Ma HN, Li HL, Che W. Effect of exchange of tracheal tube for laryngeal mask airway (LMA) on intratracheal extubation stress response under deep anesthesia level after surgery in elderly patients with hypertension. Zhonghua Wai Ke Za Zhi. 2010;48(23):1811–1814. 3. Valley RD, Freid EB, Bailey AG, et al. Tracheal extubation of deeply anesthetized pediatric patients: A comparison of desflurane and sevoflurane. Anesth Analg. 2003;96(5):1320– 1324. 4. Koga K, Asai T, Vaughan RS, et al. Respiratory complications associated with tracheal extubation. Anesthesia. 1998;53(6):540–544.

5. Suzuki A, Ogawa H. A new technique of extubation using laryngeal mask in the neurosurgical anesthesia. Masui. 1997;46(7):994–996.

6. Smith I, Taylor E, White PF. Comparison of tracheal extubation in patients deeply anesthetized with desflurane or isoflurane. Anesth Analg. 1994;79(4):642–645.

7. Valley RD, Ramza JT, Calhoun P, et al. Tracheal extubation of deeply anesthetized pediatric patients: A comparison of isoflurane and sevoflurane. Anesth Analg. 1999;88(4):742–745. 8. Higuchi H, Ura T, Taoda M, et al. Minimum alveolar concentration of sevoflurane for tracheal extubation in children. Acta Anaesthesiol Scand. 1997;41(7):911–913. 9. Forestner JE, McGraw SA, Norman PF. Laryngeal papillomatosis: Anesthetic management. South Med J. 1979;72(9):1107–1112. See Also (Topic, Algorithm, Electronic Media Element) • Laryngospasm • Superior laryngeal nerve • Recurrent laryngeal nerve • Aspiration

CLINICAL PEARLS

• Deep extubation is a technique that can be used in certain circumstances when minimal hemodynamic change is advantageous, or where avoidance of coughing and bucking would be beneficial. • The major drawback is that the anesthetist is relinquishing a known secured airway for an unsecured one. • Deep extubation does have uses, but serious negative complications can result if not vigilant about the technique.

DEFIBRILLATION Jochen Steppan, MD Nanhi Mitter, MD

BASICS DESCRIPTION

• Defibrillation is the application of electricity during cardiac arrest either to the chest wall or directly to the heart muscle to restore a coordinated cardiac rhythm and a spontaneous circulation. • The first scientific work on defibrillation was published by a team of researchers at the Johns Hopkins University in 1933. Funding was provided from an electrical company as a result of an increase in the rate of sudden death among utility workers who were rewiring American homes with electricity. This work was followed by the development of closed chest cardiac massage by the same team and publication in 1960. PHYSIOLOGY PRINCIPLES

• Adequate current flow through the heart is required for successful defibrillation: I = V/R, where I = current, V = voltage, and R = resistance. Therefore, for the same voltage (V) applied, the current (I) delivered to the patient varies depending on the transthoracic impedance (R). • Transthoracic impedance (70–80 Ohm) is influenced by: – Electrode surface area: Electrodes should be 8–12 cm in diameter for adults. Large electrode pads result in smaller transthoracic impedance. – Pressure on the electrodes: As per the American Heart Association guidelines, a force of 8 kg applied to paddles results in an optimal reduction of transthoracic impedance. – Body habitus and tissue properties of the rib cage, muscle, subcutaneous fat and skin contribute to transthoracic impedance. In order to further reduce transthoracic impedance, a conductive material such as gel pads or electrode paste should be used. • There is no direct relationship between the energy applied (Energy = Power × Time) and current flow. • Theories about mechanisms of defibrillation: – Critical mass theory (original): The delivery of current to a critical mass of myocardium can stun and make the muscle unexcitable. The uncoordinated waveforms of excitation that perpetuate ventricular fibrillation would then be extinguished and a normal cardiac excitation will resume. Tissue in close proximity to the shocking electrodes produces virtual electrodes that either hyperpolarize or depolarize the surrounding cardiac tissue. – Vulnerability theory (newer): Defibrillation is mediated by depolarizing fully excitable cells and also by depolarizing cells in the relative refractory period by a stimulus that exceeds the upper limit of vulnerability. • Defibrillator waveforms: – Monophasic defibrillators deliver current in one direction (one polarity).

– Biphasic defibrillators deliver current in 2 directions. The current flows in one direction during the first phase of the waveform and in the opposite direction during the second phase. Therefore, lower energy levels can be used during defibrillation for equivalent or higher success rates. – No specific waveform has shown to be consistently associated with a greater incidence of return of spontaneous circulation or higher survival to hospital discharge. – All newer defibrillators deliver biphasic shocks, but monophasic shocks are still acceptable and currently in clinical use.

ANATOMY

• Physiological cardiac excitation is initiated in the sinus node. It travels through atrial tissue to the AV node and is then conducted through the bundle of His to the bundle branches over the Purkinje fibers and finally to the myocardium. • Ventricular fibrillation (Vfib) is a state of disorganized electrical activity that leads to uncoordinated contraction of the myocardium, making its ejection ineffective.

DISEASE/PATHOPHYSIOLOGY

Cardiac arrest is a leading cause of death in many parts of the world. • In the US and Canada, approximately 350,000 people suffer a cardiac arrest per year and require resuscitation (half of the cases occur in-hospital). • The incidence of in-hospital cardiac arrests is estimated at 3–6/1,000 admissions. • For every minute that elapses between collapse and defibrillation, the chance of survival from ventricular fibrillation diminishes by 7–10% every minute if no CPR is provided and by 3–4% with CPR. • Defibrillation is the only effective treatment of Vfib and should be performed within 10 minutes after sudden onset cardiac arrest (<3 minutes in hospital) to achieve a good neurologic outcome. PERIOPERATIVE RELEVANCE

• External (transthoracic) defibrillation: – Initial energy level: For biphasic defibrillators, follow the recommendations by the manufacturer. If those are not readily available, it is reasonable to start with 150–200 J when using a biphasic defibrillator to treat Vfib/pulseless ventricular tachycardia (Vtach), and it is optional to increase up to 360 J for subsequent shocks or to continue with the initial amount of energy. The recommendation for monophasic defibrillators is to use 360 J for the initial and all subsequent shocks. – Unsynchronized shock describes the delivery of a shock that is not synchronized with the QRS wave. As there is no organized electrical activity during Vfib or pulseless Vtach, this is the treatment of choice for those entities and an integral part in the treatment of sudden cardiac arrest. – Pads or paddles: To decrease transthoracic impedance one should use gel pads or electrode paste (American guidelines only), shave the chest if it does not delay chest compressions or shock delivery, and press the paddles firmly to the chest (8 kg of force). Can be placed in the following positions: Antero-lateral (default location), antero-

posterior, anterior-left infrascapular, or anterior-right infrascapular position. There are no studies in patients with Vfib or pulseless Vtach directly comparing the effects of electrode positioning to success of defibrillation. Therefore, practical considerations usually dictate electrode placement to optimize current flow through the patient’s heart. In adults, antero-lateral placement is favored, while in children the antero-posterior placement is often used in order for the pads not to overlap. In patients with an implantable cardioverter defibrillator (ICD), pads should be placed at least 8 cm away from the device in an anterior-posterior or anterior-lateral position. Do not place pads or paddles directly over transdermal medication patches because the patch may block the delivery of energy and may cause burns to the skin. – Pediatric: Energy levels should start at 2 J/kg and can be escalated up to 10 J/kg (not to escalate the adult maximum dose). In children aged 1–8 years, pediatric electrodes should be used. Pads or paddles should be applied with 5 kg of force and can be in the following positions: Antero-apical, antero-posterior, or apex-posterior position. • Temporary transvenous defibrillation can be considered as an alternative in patients undergoing electrophysiological procedures. • ICDs are usually implanted underneath the pectoral muscle below the left clavicle and defibrillate with 40 J of energy via an internal pacing wire embedded in the right ventricle (up to 8 times per detected Vfib/Vtach).

EQUATIONS

• I = V/R, where I = current, V = voltage, R = resistance • Energy = power × time

GRAPHS/FIGURES

• 2010 ACLS Cardiac Arrest Algorithm for Vfib or pulseless Vtach arrest: – Activate Emergency Response System – Start CPR, administer oxygen, attach monitor/defibrillator – Confirm Vfib or pulseless Vtach and defibrillate – Continue CPR for 2 minutes and establish intravenous/intraosseous access – Check rhythm: If shockable, defibrillate; otherwise proceed with ACLS pathway for asystole/PEA, or postcardiac arrest care – Continue CPR for 2 minutes, administer epinephrine every 3–5 minutes, consider advanced airway and capnography – Check rhythm: If shockable defibrillate; otherwise proceed with ACLS pathway for asystole/PEA, or postcardiac arrest care – Continue CPR for 2 minutes, give amiodarone and treat reversible causes – Repeat check rhythm. • For witnessed cardiac arrest, 1 shock followed immediately by CPR is favored over 3 stacked shocks. The European guidelines allow consideration of 3 stacked shocks in the early postoperative period following cardiac surgery, in the catheterization lab, or when the patient is already connected to a defibrillator and the cardiac arrest is witnessed.

REFERENCES

1. Jacobs I, Sunde K, Deakin CD, et al. Part 6: Defibrillation. 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Circulation. 2010;122(16 Suppl 2):S325–S337.

2. Link MS, Atkins DL, Passman RS, et al. Part 6: Electrical therapies: Automated external defibrillators, defibrillation, cardioversion, and pacing. 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 Suppl 3):S706–S719. 3. Haskell SE, Atkins DL. Defibrillation in children. J Emerg Trauma Shock. 2010;3(3):261– 266. 4. Deakin CD, Nolan JP, Sunde K, et al. European Resuscitation Council Guidelines for Resuscitation 2010. Section 3: Electrical therapies: Automated external defibrillators, defibrillation, cardioversion and pacing. Resuscitation. 2010;81(10):1293–1304. 5. Dosdall DJ, Fast VG, Ideker RE. Mechanisms of defibrillation. Annu Rev Biomed Eng. 2010;12:233–258. 6. Hooker DR, Kouwenhoven WB, Langworthy O. The effect of alternating electric currents on the heart. Am J Physiol. 1933;103:444–454. 7. Travers AH, Rea TD, Bobrow BJ, et al. Part 4: CPR overview. 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 Suppl 3):S676–S684.

ADDITIONAL READING

• Neumar RW, Otto CW, Link MS, et al. Part 8: Adult advanced cardiovascular life support. 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 Suppl 3):S729–S767.

See Also (Topic, Algorithm, Electronic Media Element) • Ventricular fibrillation • Ventricular tachycardia • Operating room fires

CLINICAL PEARLS

• During external defibrilation, avoid an oxygen-rich environment as this might lead to an increased risk of fire (remove insufflations of oxygen over the field of defibrillation as well as face masks or nasal cannulas; however, keep endotracheal tubes connected to the ventilator). • Automated external defibrillators (AEDs) are easy-to-use, computerized devices that use voice and visual prompts to aid lay rescuers and healthcare professionals to safely defibrillate Vfib and pulseless Vtach. AEDs automatically analyze a surface ECG signal and recommend the delivery of a shock, if indicated. The use of AEDs in combination with CPR in public locations (airports, casinos, sports facilities) has doubled the number of survivors

in those public areas.

DEMENTIA

Kamilia S. Funder, MD Jacob Steinmetz, MD, PhD

BASICS DESCRIPTION

• Dementia describes a progressive loss of intellectual functions such as memory, learning, problem solving, and abstract thinking, resulting in occupational and social decline. Consciousness remains unaffected. • It can be classified into different subtypes: – Alzheimer’s disease dementia (AD); accounts for 50% of all cases – Vascular dementia – Lewy body dementia – Parkinson’s dementia – Frontotemporal dementia EPIDEMIOLOGY Incidence

4.6 million new cases worldwide each year and doubling every 20 years (1)

Prevalence

• 29 million people suffer from dementia globally. • Affects 4% of people above 60 years of age • Doubles with every 5-year increase in age • More prevalent in developing countries

Morbidity

• Impaired social and occupational functioning • Higher risk of depression

Mortality

• Accounts for 3.4% of all deaths in high-income countries • Limited treatment and poor prognosis

ETIOLOGY/RISK FACTORS

• Highly associated with advancing age • Degenerative neuropathological changes such as cerebral atrophy and plaques (2) • Cerebrovascular disease (CVD) • Female gender

PATHOPHYSIOLOGY

• The pathogenesis is not fully uncovered; it is likely the result of complex interactions between genes, lifestyle factors, and other environmental influences. • Mutations in genes that control the production of proteins like amyloid precursor protein (APP), presenilin 1+2, and apolipoprotein E (apoE), may play a role. • Evidence suggests that triggers, such as protein aggregation (e.g., Lewy bodies), accumulation of β-amyloid plaques, infection, inflammation, and hypothermia, may play a role.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess cognitive function and optimize the perioperative setting accordingly in order to minimize external stress • Optimize physical health status • Restrict drug usage to avoid drug interactions and polypharmacy; carefully titrate all medications • Patience is crucial

PREOPERATIVE ASSESSMENT SYMPTOMS

• Problems with concentration, language, and ability to recognize objects/family members (2) • Memory loss, especially short-term memory • Later: Irritability, agitation, apathy

History

• Type and severity of dementia; recent worsening • Family history • Concurrent diseases, including atherosclerosis, and diabetes • Smoking and alcohol use • Current activity level • Social relations and adequacy of home care • Cognitive capacity

Signs/Physical Exam

• Identify any signs of stroke and perform a neurologic examination • Difficulty comprehending detailed information • Exclusion of any treatable, reversible condition such as depression, delirium, intoxication, and normal pressure hydrocephalus

TREATMENT HISTORY None

MEDICATIONS

• Antidepressants • Anti-Parkinson drugs. Reports suggest that Selegiline (MAO-B inhibitor) in combination with meperidine/pethidine may cause agitation and muscle rigidity (3). Before the use of

decarboxylase inhibitors, peripheral conversion of L-DOPA to dopamine may have caused orthostatic hypotension because of peripheral vasodilatation (4). • Anxiolytics • Acetylcholinesterase inhibitors may decrease the duration of muscle relaxants. • Herbal supplements

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Minimal Mental State Examination (MMSE) to assess cognitive skills • Laboratory tests: CBC, electrolyte status, blood glucose test, only rarely consider thyroid and thyroid-stimulating hormone levels, Urineanalysis including toxicology screen

CONCOMITANT ORGAN DYSFUNCTION

• Neurologic deficits • Possible altered pain perception and drug sensitivity (2)

CIRCUMSTANCES TO DELAY/CONDITIONS

• Suboptimal physical health and unstable psychiatric patients • Failure to obtain informed consent from patient or representative (e.g., family member)

CLASSIFICATIONS

Severity of dementia can be classified according to the MMSE. Maximum score is 30: • Score ≥25 indicates no cognitive impairment. • Score between 21 and 24 indicates mild dementia. • Score from 10 to 20 indicates moderate dementia. • Score <10 corresponds to severe dementia.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Preoperative analgesics should be administered similar to other frail patients. • If an anxiolytic is indicated, utilize short-acting benzodiazepines. • Neuroleptics are best avoided because of a potential increased risk of extrapyramidal side effects. Demented patients may be particularly sensitive (5). • If antipsychotics are warranted, risperidone and clozapine are generally better tolerated than haloperidol (2). Special Concerns for Informed Consent

• Require great patience • Correction of sensory deficit (e.g., hearing aid and glasses) to facilitate the patient’s perception • Assessment of the ability to make informed consent by ensuring that the patient is able to

retain and process the information given. Help from family members is often needed.

INTRAOPERATIVE CARE Choice of Anesthesia

• No significant advantage of regional anesthesia compared to general anesthesia, but may improve recovery and minimize opioid use (2). • Inhalational anesthetics might be easier to adjust individually, using end-tidal concentration, compared to intravenous anesthesia (2). • Intravenous anesthetics should, in general, be titrated and given in smaller doses to elderly demented patients secondary to altered pharmacodynamics and pharmacokinetics. – Decreased renal and hepatic clearance due to decreased organ mass and blood flow in the elderly – Decreased volume and rate of distribution; dependent on protein binding, cardiac output, and blood volume which are altered in the elderly – Increased drug sensitivity (2) • Risk of opioid-induced muscle rigidity • Risk of hyperkalemia following succinylcholine, especially in patients with neuromuscular disorders (e.g., Parkinson’s dementia)

Monitors

• Standard ASA monitors • Consider arterial blood pressure monitoring • Foley catheter to monitor urine output and thereby hemodynamic status (or to avoid the mess that may be made from incontinence) • Bispectral index (BIS) monitoring may assist the administration of hypnotics, by measuring the depth of anesthesia. Baseline BIS might be lower in demented patients (2).

Induction/Airway Management

• Reduce induction medication doses and administer slowly to avoid excessive hemodynamic depression and prolonged recovery • Vasopressor agents should be easily available. • Be aware of previous history of difficult intubation. Limited head and neck movement may impede tracheal intubation; prepare to have an alternative airway management plan. • Neuromuscular blocking agents (NMBAs) should be used with caution because of risk of drug interactions, especially combined with acetylcholinesterase inhibitors used for treating AD (2).

Maintenance

• Volatile anesthetics: Use end-tidal concentrations to maintain adequate dose. MAC can be reduced by 30–50% in patients above 80 years of age (2). • Intravenous anesthetics should be infused at lower rates in order to maintain a lower plasma concentration. • Avoid bolus injections. Because of altered pharmacokinetics and pharmacodynamics, the administration of anesthetics and pain-relieving treatments should be carefully titrated to minimize the risk of adverse drug effects or excessive responses.

• Avoid perioperative hypothermia. Elderly patients are more prone to hypothermia as a result of reduced metabolism, and animal studies suggest that hypothermia might be an independent risk factor for Alzheimer’s disease (2). • Avoid antiemetics with anti-dopaminergic properties

Extubation/Emergence

• Dose reduction of anesthetics and analgesics will help promote an uneventful recovery. • Shorter-acting drugs may be beneficial.

POSTOPERATIVE CARE BED ACUITY

• Continue close monitoring • Encourage quick mobilization by sufficient pain control. Consider using The MobilizationObservation-Behavior-Intensity-Dementia (MOBID) pain scale. • Ensure calm surroundings to aid the patients sleep and minimize stress

MEDICATIONS/LAB STUDIES/CONSULTS

• Early discharge can help facilitate a patient’s return to well-known surroundings. • Resume daily medication

COMPLICATIONS

• Hemodynamic depression • Hypothermia • Delirium • Postoperative cognitive dysfunction (POCD) • Unrecognized pain • Reduced compliance

REFERENCES

1. Ferri CP,Prince M, Brayne C, et al. Global prevalence of dementia: A Delphi consensus study. Lancet. 2005;366:2112–2117. 2. Funder KS, Steinmetz J, Rasmussen LS. Anesthesia for the patient with dementia. J Alzheimer Dis. 2010;22(Suppl 3):129–134. 3. Zornberg GL, Bodkin JA, Cohen BM. Severe adverse interaction between pethidine and selegiline. Lancet. 1991;337:246. 4. icholson G, Pereira AC, Hall GM. Parkinson’s disease and anaesthesia. Br J Anaesth. 2002;89:904–916. 5. Pijnenburg YA, Sampson EL, Harvey RJ, et al. Vulnerability to neuroleptic side effects in frontotemporal lobar degeneration. Int J Geriatr Psychiatry. 2003;18:67–72. 6. World Health Organization (WHO). www.who.int/en/ See Also (Topic, Algorithm, Electronic Media Element)

• Postoperative cognitive dysfunction • Postoperative delirium • Hypothermia

CODES ICD9

• 294.10 Dementia in conditions classified elsewhere without behavioral disturbance • 294.20 Dementia, unspecified, without behavioral disturbance • 331.0 Alzheimer’s disease ICD10

• F01.50 Vascular dementia without behavioral disturbance • F03.90 Unspecified dementia without behavioral disturbance • G30.9 Alzheimer’s disease, unspecified

CLINICAL PEARLS

• Patience is essential. Obtain help and information from family membe • Careful drug titration; onset is delayed. • Huge variability in physical status of the elderly, but co-morbidity is common.

DENTAL DAMAGE David W. Lui, DMD, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Amongst the most common claim against anaesthetist. Damage can occur from laryngoscopy, hard suction catheters, and the insertion, removal, or biting on emergence of the airway device or oral airway. • The incidence increases in patients with pre-existing dental disease, difficult and emergent intubations, or the skill of the laryngoscopist. • Types of damage include avulsions (complete removal), damage to crowns and bridges, dislocation, and fractures. EPIDEMIOLOGY Incidence

• Damage is difficult to assess due to inconsistent reporting or recognition; ranges from 0.02% to 12.1% (1). • Dental injury requiring dental intervention is estimated to occur in 1:4,500 anesthetics (1). • Damage in the setting of: – Difficult intubation: 20% of all cases – >2 laryngoscopy attempts: 1–4% – Trainees/level of training: Surprisingly incidence amongst residents is lower than “experienced” hands (1,2,3) • Damage during: – Intubation: 50–75% – Extubation or recovery room: 9–20% (2) • Maxillary incisors (#8, #9) are most commonly injured. • Types of damage: – Enamel fractures and partial dislocation: 55.2% – Avulsion: 9% – Crown fracture: 7.7% (3)

Prevalence

Age 45–65 years: Approximately 2/3rd of all claims Morbidity

Aspiration of the tooth or fragments, particularly if it goes unnoticed or unrecognized ETIOLOGY/RISK FACTORS

• Laryngoscopy in the setting of:

– Difficult intubations; small mouth opening, prominent upper teeth, poor neck mobility, large neck, and small thyromental distance – Emergency intubations – Pre-existing dental condition; caries, periodontitis – Restorations, prosthetics; synthetic materials may not be as “hard” as natural enamel (1,2,3). • Traumatic insertion, removal, or biting of the airway device or oral airway • Hard suction catheters

PHYSIOLOGY/PATHOPHYSIOLOGY

• There are 16 maxillary teeth and 16 mandibular teeth. The Universal Numbering System provides a method to identify teeth: Maxillary teeth are #1–16 and mandibular teeth are #17–32. • The tooth is composed of a crown (enamel and dentin) and the root (cementum and pulp): – Enamel is the exposed portion of the tooth. It is composed of mineralized substances and is the hardest substance in the human body. – Dentin lies directly underneath and is softer than enamel. However, it functions to provide a foundation or framework. – Cementum is a specialized bony substance covering the root of a tooth. It functions in providing a substance to which the periodontal ligaments can attach to. – Pulp is the innermost portion. It contains nerves and blood vessels and connects to the gums. • The periodontium is composed of the periodontal ligaments, gingiva, and alveolar bone. • Laryngoscopy: Blades attached to a handle are utilized to displace the tongue and epiglottis in order to insert the endotracheal tube. They are composed of metal and are inflexible and noncompliant. Optimal patient positioning and laryngoscopy technique aim to align the oropharynx, hypopharynx, and larynx in order to attain direct visualization of the glottis opening. – In the event that this alignment is not, or cannot, be achieved, the laryngoscopist may be more likely to “crank” the wrist and utilize the maxillary teeth (maxillary central incisors #8, #9) as a fulcrum. – In addition to the vulnerable location during laryngoscopy, teeth #8 and #9 are single rooted and have a small cross-sectional area. – These 2 incisors are estimated to be involved in >90% of reported instances of dental damage. • Airway devices: Endotracheal tubes, laryngeal mask airways, bite blocks, and oral airways can cause damage during insertion, removal, or biting during emergence. • Pre-existing dental conditions increase the risk of dental injury. – Cavities or caries consist of a bacterial process that causes rotting of the root. – Periodontal disease consists of gingival inflammation, alveolar bone loss, and tartar buildup. • Restorations and prosthetics increase the risk of dental injury: – Bridges: Replacement of one or more missing teeth. A pontic is fused between 2 porcelain crowns to fill in the space left by the missing teeth. – Bonding: Restoration of decaying teeth or cosmetically improving teeth (discoloration,

abnormal shapes, small gaps). A composite resin filling is applied to the anterior face of the tooth, followed by a bonding material that can be shaped or colored to achieve the desired result. – Veneers: Improvement cosmetically of discolored, worn, chipped, or misaligned teeth – Crowns: Coverage of the visible surface of a decayed or worn-down tooth in order to reduce further wearing down • Pulmonary aspiration of foreign body: Detection requires identification of the event. Any missing tooth should be assumed to have been aspirated until proven otherwise. A chest radiograph can identify the presence and location.

PREVENTATIVE MEASURES

• Preoperative evaluation and assessment of the airway should include the dentition: – Loose teeth – Chips – Fractures – Restoration or prosthetics (crowns, bridges, veneers, bonding) – Periodontal disease • Documentation preoperatively: If pre-existing dental disease is present, the patient should be informed and findings should be confirmed with the patient. Documentation should include a careful description of the preoperative evaluation record. • Consent: Anesthesia consent should include a verbal discussion, followed by a written consent that is signed by the patient or their designated caretaker/power of attorney regarding the possibility of dental injury. More time or attention should be given to those with pre-existing dental disease or anticipated difficult intubation. • Alternative airway management: – Anticipated difficult intubation: May be prudent to preemptively utilize special airway management tools such as fiberoptic bronchoscopy, indirect laryngoscopy tools (GlideScope, etc.), laryngeal mask airway guided intubation, etc. If laryngoscopy is to be attempted, consider special angulated blades (McCoy, Belscope), plastic blades, or blades with soft heels. – Unexpected difficult airways: Consider alternative devices early to avoid repeated laryngoscopy attempts and fulcruming the laryngoscope. • Standard and routine laryngoscopy: Should avoid teeth with gentle insertion and advancement. Proper patient positioning (head, neck, shoulder rolls, ramps), preoxygenation (“buys time” before desaturation), and avoidance of “cranking” the wrist should always be performed. • Tooth guards: Routine use is controversial. They may impair visualization, insertion of the endotracheal tube, or increase apneic time. One study demonstrated that insertion increased intubation time by 7 seconds (statistically significant) (4). • Insertion and removal of airway devices and bite blocks should always be done gently. Laryngeal mask airways have a thicker diameter and are less compliant than endotracheal tubes. Avoid forceful pulling and removal of items while the patient is biting (downward movement). • Soft bite blocks constructed from gauze may reduce damage from biting of the endotracheal tube. Consider utilizing when motor evoked potentials are being performed.

• Dental consultation and treatment prior to surgery for dentition “at risk” for avulsion or further damage may prevent or reduce the incidence of damage. If this is not feasible, one technique that has been suggested is the wrapping of suture around the gingival margins several times and taping the other end to the cheek. • Studies have suggested that despite careful attention to poor dentition, the risk of dental lesions cannot be completely eliminated.

DIAGNOSIS • Visual inspection after routine intubation with documentation in the anesthetic record may reduce ambiguity postoperatively. • Visual inspection following a difficult or traumatic intubation, suctioning, insertion or removal of other airway devices is always suggested (1). • Missing teeth should be assumed to have been aspirated until proven otherwise. A chest radiograph can easily rule out this possibility.

DIFFERENTIAL DIAGNOSIS

Pre-existing chips, fractures, missing teeth (a careful preoperative evaluation will remove any doubts or confusion)

TREATMENT • Dental consultation • Avulsed and retrieved. Transport medium of choice is Hanks Balanced Salt Solution, followed by cool milk, saliva, and cool saline. In the operating room, cool saline may be the most easily available. • Avulsions may require repositioning and splinting with non-rigid fixation (wire) for 7–10 days. • Tooth fractures can range from composite bonding, to root canal therapy (with coronal restoration), to dental extraction, depending on the size/depth/location of the fracture. • Alveolar fractures require segmental arch bar placement. • Consider antibiotics and Peridex oral rinse in the event of any dental or intraoral injury. If the damage extends extraorally, check for tetanus status and vaccinate if indicated.

FOLLOW-UP • A discussion with the patient and family should inform them of the situation as well as the immediate efforts that will be taken to remedy the situation (dental consultation). • Dental consultation may be coordinated while an inpatient if appropriate. • Reimbursement may be considered as per department, group, or hospital policy.

CLOSED CLAIMS DATA

• Reported to the National Practitioner Data Bank • Estimated to be as high as 1/3rd of all claims against anesthesiologis (3)

REFERENCES

1. Yasny JS. Perioperative dental considerations for the anesthesiologist. Anesth Analg. 2009;108(5):1564–1573. 2. Rosa Maria G, Paolo F, Stefania B, et al. Traumatic dental injuries during anaesthesia. Part 1: Clinical evaluation. Dental Trauma. 2010;26(6):459–465. 3. Warner ME, Benenfeld SM, Warner MA, et al. Perianesthetic dental injuries. Anesthesiology. 1990;90:1302–1305. 4. Brosnan C, Radford P. The effect of a toothguard on the difficult of intubation. Anaesthesia. 1997;52:1011–1012.

ADDITIONAL READING

• Gasier RR, Castro AD. The level of anesthesia resident training does not affect the risk of dental injury. Anesth Analg. 1998;87:255–257. • Givol N, Gershtansky Y, Halamish-Shani T, et al. Perianesthetic dental injuries: Analysis of incidence reports. J Clin Anesth. 2004;16:173–176. • Newland MC, Ellis SJ, Peters KR, et al. Dental injury associated with anesthesia: A report of 161,687 anesthetics given over 14 years. J Clin Anaesth. 2007;19:339–345.

See Also (Topic, Algorithm, Electronic Media Element) • Difficult airway

CODES ICD9 • 525.11 Loss of teeth due to trauma • 525.63 Fractured dental restorative material without loss of material • 525.64 Fractured dental restorative material with loss of material ICD10 • S03.2XXA Dislocation of tooth, initial encounter • S02.5XXA Fracture of tooth (traumatic), init for clos fx • S02.5XXB Fracture of tooth (traumatic), init encntr for open fracture

CLINICAL PEARLS

• A preoperative exam of dentition should be performed on every patient receiving an anesthetic. Additionally, in the event of pre-existing disease, it should be confirmed with the patient and appropriately documented in the preoperative evaluation. • Routine examination following airway management may reduce the ambiguity of preexisting or postoperative incidents that can be misconstrued or mislabeled as intraoperative dental damage. In patients in whom injury may have occurred (difficult intubation, traumatic insertion or removal of airway devices or oral airway, biting down on the suction

catheter) it is prudent to do so. • Identification of dental damage should be discussed with the patient, and appropriate follow-up should be determined and coordinated.

DEPRESSION

Dmitri Souzdalnitski, MD, PhD Samuel Samuel, MD

BASICS DESCRIPTION

• Major depressive disorder (also known as “depression”) can be diagnosed on the basis of one or more major depressive episodes. The symptoms cause significant distress as well as impairment in social, occupational, and/or other important areas of functioning. • Symptoms persist for longer than 2 months and are characterized by distinct functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. • The diagnostic criteria for a depressive episode requires that 5 (or more) of the following symptoms have been present during a 2-week period and represent a change from previous function (1)[A] and that at least one of the symptoms has to be either a depressed mood or (2) loss of interest or pleasure: – Depressed mood – Noticeably diminished interest or pleasure – Significant weight loss (when not dieting) or weight gain, or decrease/increase in appetite – Insomnia or hypersomnia – Psychomotor agitation or retardation – Fatigue or loss of energy – Feelings of worthlessness or excessive/inappropriate guilt – Diminished ability to think or concentrate, indecisiveness – Frequent thoughts of death or suicide

EPIDEMIOLOGY Incidence

2.0–4.5 per 1,000 persons per year (2)[B]

Prevalence

• Lifetime prevalence rates for significant depressive symptoms are 11–21% and 3–7% for major depressive disorder. • Rates in women and men are highest in the 25–44 year-old age group. • Major depressive disorder is about 2–3 times as common in adolescent and adult females as in adolescent and adult males. • In children, boys and girls are affected equally.

Morbidity

Rather than producing its own morbidity, depression commonly influences the morbidity resulting from other medical conditions. For example, it complicates the management of

patients with chronic back pain. 9% of these patients take anti-anxiety medications, and 25% take antidepressants (3)[B]. Mortality

• One in 7 patients with major depressive disorder eventually dies by suicide. • Major depression accounts for about half of suicides, which are the 8th leading cause of death in the US.

ETIOLOGY/RISK FACTORS

• Various genetic, biological, or psychosocial models have been implicated in the etiology of depression. However, the exact cause of major depressive disorder is not known. • The traditional thinking that depression follows a triggering event, such as emotional trauma, has been observed in fewer than 20% of patients. The following risk factors have also been observed: – Alcohol or drug abuse – Loneliness – Inadequate social support – Remote significant emotional trauma – Recent negative life events – Financial problems – Unemployment or underemployment – History of depression in the family – Medical problems, chronic pain – Early childhood trauma or abuse – Marital or relationship problems – Terminally or severely ill children – Insecure

PATHOPHYSIOLOGY

• The exact mechanism of development of major depressive disorder is unknown. Commonly discussed mechanisms are: – Biological: Genetically mediated neurotransmitter misbalance of norepinephrine, serotonin, dopamine, acetylcholine, gamma-aminobutyric acid, melatonin, glycine, histamine, etc. – Neuroendocrine and hormonal mechanisms: Corticotropin-releasing hormone, endorphins, enkephalins, vasopressin, cholecystokinin, substance P, thyroid and adrenal hormones, and others – Psychoanalytic, psychodynamic, and behavioral mechanisms

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Literature recommends that anesthetist be more sensitive to the psychological concerns in depressed patients who are undergoing surgery. • Antidepressants are important elements in the treatment of depression and should be continued in the perioperative period with certain exceptions (discussed in the “Medications” section).

PREOPERATIVE ASSESSMENT SYMPTOMS

• Commonly reported symptoms are: – Depressed mood – Feelings of helplessness and hopelessness – Anhedonia – Irritability or restlessness – Change in appetite • Weight changes • Unexplained aches and pains • Change in sleep • Change in body activity • Loss of interest in daily activities • Loss of energy • Feelings of worthlessness • Excessive or inappropriate guilt • Indecisiveness or decreased concentration • Suicidal ideation

History

• Clues to potential depression also include the general appearance and manners of communication of the patient. • Review relevant medical records, including history of suicide, emotional trauma, domestic violence, abuse, etc. • Family history may be helpful as well. For example there is a high risk for clinical depression in families with history of depression (7%) or alcoholism (8%).

Signs/Physical Exam

• Physical exam findings may demonstrate poor eye contact, malnutrition, disheveled appearance, or other evidence of poor personal hygiene. • A further exam may reveal certain personality changes. They might be worried, introverted, stress sensitive, obsessive, unassertive, very dependent.

TREATMENT HISTORY

• Outpatient counseling • Psychiatric admissions • Electroconvulsive therapy

MEDICATIONS

• Selective serotonin reuptake inhibitors (SSRIs) • Serotonin/norepinephrine reuptake inhibitors (SNRIs) • Tricyclic antidepressants (TCAs) • Monoamine oxidase inhibitors (MAOIs) • Lithium

• Antipsychotics

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

Not applicable to the anesthetist

CONCOMITANT ORGAN DYSFUNCTION

It is not uncommon to have concurrent chronic pain problems. If this is the case, the perioperative pain management should be carefully planned and discussed with the patient in details. CIRCUMSTANCES TO DELAY/CONDITIONS

Typically, cases are not delayed because of depression. CLASSIFICATIONS

• Major depression (one or more episodes) • Melancholic subtype • Atypical depression • Seasonal affective disorder

TREATMENT PREOPERATIVE PREPARATION Premedications

Benzodiazepines to decrease preoperative anxiety Special Concerns for Informed Consent

No special concerns for informed consent INTRAOPERATIVE CARE Choice of Anesthesia

General or regional, or MAC anesthesia for routine cases Monitors

Standard ASA monitors

Induction/Airway Management

• Serum cholinesterase activity may decrease in patients treated with phenelzine; thus, the dose of succinylcholine may need to be reduced. • Ketamine should be avoided in patients taking MAOIs since it may exaggerate the sympathetic stimulation. Maintenance

• Any volatile anesthetic with or without nitrous oxide is acceptable for maintenance of

general anesthesia. • The MAC may be higher in patients with depression because of the medications they are on (MAOIs, SSRIs, SNRIs, TCAs). • The epinephrine used for spinal anesthesia should be limited in patients taking MAOIs because of the potential of an exaggerated sympathetic response.

Extubation/Emergence

No special considerations in extubation or emergence in patients with depression

POSTOPERATIVE CARE BED ACUITY

No special considerations

MEDICATIONS/LAB STUDIES/CONSULTS

• Brief psychological screening. Also, if needed, a comprehensive assessment and assistance from mental health professionals to improve the depressed patient’s and his/her family’s experience during the acute postoperative period. • The analgesic potency has been demonstrated for some of the antidepressant medications. TCAs, duloxetine, milnacipran, and several others are approved for the treatment of chronic neuropathic or myofascial pain. These medications, therefore, may contribute to the overall effects of postoperative pain management. • SSRIs and SNRIs should be continued at preoperative dosages. • TCAS should be continued at their regular dose in the perioperative period. – Adverse effects are common, and patients should be re-evaluated if there is evidence of sedation and delirium, or other anticholinergic effects, particularly in elderly patients. – Cardiovascular risks at regular doses are extremely low.

COMPLICATIONS

• Meperidine should be avoided in combination with SSRIs (paroxetine, fluoxetine, sertraline, citalopram, and others), MAOIs, and certain other antidepressant medications (phenelzine, selegiline, tranylcypromine) since these combinations may produce somatic, autonomic, and neuropsychiatric derangements (including hyperreflexia, myoclonus, ataxia, fever, shivering, diaphoresis, diarrhea, anxiety, salivation, confusion and others, termed “serotonin syndrome”). • Less than 1% of all patients treated with antipsychotic drugs may develop a neuroleptic malignant syndrome (presenting as hyperthermia, hypertonicity of the skeletal muscles, fluctuating levels of consciousness and autonomic nervous system instability), and it is therefore advisable that patients taking antipsychotics should be very closely monitored in the perioperative period.

REFERENCES

1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed., text revision. Washington, DC: American Psychiatric Association, 2000.

2. Kruijshaar ME, Barendregt J, Vos T, et al. Lifetime prevalence estimates of major depression: An indirect estimation method and a quantification of recall bias. Eur J Epidemiol. 2005;20(1):103–111. 3. Walid MS, Robinson JS, 3rd, Robinson ER, et al. Comparison of outpatient and inpatient spine surgery patients with regards to obesity, comorbidities and readmission for infection. J Clin Neurosci. 2010;17(12):1497–1498.

ADDITIONAL READING

• Ebert TJ, Schid PG. Inhaled anesthetics. In: Barash PG, et al., eds. Clinical anesthesia, 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2009:424. • Hines RL, Marschall KE. Psychiatric disease/substance abuse/drug overdose. In: Hines RL, Marschall KE, eds. Stoelting’s anesthesia and co-existing disease, 5th ed. Philadelphia: Churchill Livingstone, 2008:533–538.

See Also (Topic, Algorithm, Electronic Media Element) • Electroconvulsive therapy • Complex regional pain syndrome type I • Complex regional pain syndrome type II

CODES ICD9 • 296.20 Major depressive affective disorder, single episode, unspecified • 296.30 Major depressive affective disorder, recurrent episode, unspecified • 311 Depressive disorder, not elsewhere classified ICD10 • F32.9 Major depressive disorder, single episode, unspecified • F33.9 Major depressive disorder, recurrent, unspecified

CLINICAL PEARLS

• Earlier recommendations suggested discontinuation of MAOIs 14 days prior to elective operations, to permit the restoration of normal enzyme activity. The current literature suggests that anesthesia can be safely administered to patients being treated with MAOIs. However, excessive sympathetic stimulation or use of sympathomimetic drugs should be limited. • Patients with a history of bipolar disorder may be on lithium. It is important to be aware of signs of acute lithium intoxication: Vomiting, profuse diarrhea, tremor, confusion, hyperreflexia, ataxia, coma, convulsions, and seizures. The toxicity can be triggered by drugs that reduce lithium excretion or increase reabsorption, such as NSAIDs, ACE inhibitors, thiazide diuretics, and metronidazole. Cardiac toxicity can be presented as sinus dysfunction, T-wave flattening, ventricular arrhythmia, and myocarditis. Lithium potentiates depolarizing and non-depolarizing neuromuscular blocking drugs causing

potentially dangerous reactions with ECT.

DIABETES INSIPIDUS Keren Ziv, MD Linzy Fitzsimons, MD

BASICS DESCRIPTION

• Diabetes insipidus (DI) describes a disease process defined by polyuria and polydipsia resulting from either: – Decreased or absent secretion of antidiuretic hormone (ADH) – Resistance to the action of ADH at the level of the kidneys • There are multiple etiologies: – Neurogenic – Nephrogenic – Dipsogenic – Gestational EPIDEMIOLOGY Incidence

• Occurs during the postoperative course in ∼30% of pituitary surgeries, although the course is usually transient • Overall incidence is difficult to obtain due to the various etiologies of DI.

Prevalence

• 1 in 25,000 • Equal prevalence in males and females

Morbidity

• Severe dehydration resulting in hypernatremia • Fever and cardiovascular collapse can occur in patients with coexisting illnesses, the elderly, or children. Mortality

Rare, especially in adults without coexisting illness. However, may occur if treatment is delayed in children or the elderly in which the disease progresses to complete cardiovascular collapse. ETIOLOGY/RISK FACTORS

• Neurogenic: Decreased production of ADH by the hypothalamus in the brain. Risk factors include: – Trauma – Tumor in the region of the pituitary or hypothalamus

– Surgery in the region of the pituitary or hypothalamus • Nephrogenic: Decreased sensitivity to ADH by the kidneys. The most common cause in children is hereditary; 90% are associated with mutations in the AVPR2 gene that encodes for a dysfunctional vasopressin receptor (V2R). In adults, acquired nephrogenic DI is usually secondary to medications such as lithium, foscarnet, cidofovir, amphotericin B, demeclocycline, as well as a result of chronic hypercalcemia and hyperkalemia. • Dipsogenic: Defect in the thirst trigger (located in the hypothalamus) which causes increased thirst and fluid intake that subsequently suppresses vasopressin secretion and increases urine output. • Gestational: During pregnancy, all women produce vasopressinase by the placenta, which breaks down ADH. When excess vasopressinase is produced, gestational DI will occur. This etiology is the most common and can be treated by desmopressin. – In a small subset of patients, the thirst mechanism is disrupted, causing DI; it is not improved with desmopressin. – DI is also associated with other diseases of pregnancy, such as preeclampsia and HELLP syndrome. In these disease processes, hepatic vasopressinase is activated, and the only treatment is delivery of the fetus.

PATHOPHYSIOLOGY

• Hypothalamus: Produces ADH in the supraoptic and paraventricular nuclei. ADH is then transported to the posterior lobe of the pituitary gland where it is stored for later use. It is released when the body senses that electrolyte and/or fluid status are unbalanced. • Kidney: The primary target for ADH and water retention; the hormone acts on the collecting ducts and distal convoluted tubules (DCT) to allow more water to be reabsorbed into the systemic circulation and therefore create a more concentrated urine. • Thirst sensation: Also regulated by the hypothalamus when it senses decreases in serum osmolarity. • In DI, either ADH secretion is deficient or the renal response to ADH is abnormal. This results in the following pathology: – Increased urine output; water remains in the urine (polyuria) – Decreased body water (dehydration) – Increased serum [Na+] – Increased serum osmolality – Decreased urine osmolality or specific gravity – Decreased urine [Na+] – No change in total body sodium – No change in urine sodium excretion

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The possibility of DI should be evaluated in patients who present perioperatively with hypernatremia or excessive urine output; in particular, those who have had traumatic injury, tumor, status post surgery in the region of the pituitary or hypothalamus, or are pregnant. • In patients with known DI, electrolyte abnormalities may be present perioperatively. It is important to have recent chemistry labs done prior to anesthesia. Treatment may need to be

administered perioperatively by the anesthetist.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Polyuria (4–18 L/day) with acute onset, usually within 24–48 hours of neurosurgery • Polydipsia, often with a craving for cold fluids • Hypovolemia: Depending on whether thirst mechanism is intact • Nocturia, enuresis in children, anorexia, fatigue

History

• Central DI usually presents abruptly in patients with pituitary/hypothalamic surgery, head trauma, or malignancy. • Familial nephrogenic DI presents in early childhood. • Psychogenic polydipsia may have a long history.

Signs/Physical Exam

• Minimal typically • Dehydration • In rare cases, there may be bladder enlargement

TREATMENT HISTORY

When patients are awake, they can usually drink enough fluids to replace their urine losses. Patients with inadequate thirst, however, may be treated with dextrose and water or IV fluid that is hypoosmolar with respect to the patient’s serum. Serum sodium should not be reduced too quickly, ideally only 0.5 mEq/L/hr. MEDICATIONS

• ADH therapy: Desmopressin (DDAVP) is a synthetic analog to endogenous vasopressin but with greater platelet and antidiuretic effects and decreased blood pressure effects. It binds to V2 receptors in the renal collecting duct, causing increased water reabsorption in the

kidney (increased urine osmolality, decreased urine output, and no effect on sodium, potassium, or creatinine reabsorption. – Intravenous: 1–2 mcg BID, onset 15–50 minutes – Oral: 0.05 mg BID, onset 60 minutes – Nasal: 5–40 mcg BID – The duration of action is highly variable and lasts from 5 to 21 hours. Additionally, it is renally excreted; thus, renal failure will prolong its action and dosage adjustments should be considered.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Urine specific gravity <1.005 • Urine osmolality <200 mOsm/L

• Serum [Na+] >145 mEq/L • A trial with desmopressin is used to distinguish between neurogenic and nephrogenic causes. If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient, and the kidney is normal. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity. • MRI technology is being explored as a diagnostic tool.

CIRCUMSTANCES TO DELAY/CONDITIONS

Electrolyte abnormalities and dehydration may require optimization prior to surgery. CLASSIFICATIONS • Neurogenic • Nephrogenic • Dipsogenic • Gestational

TREATMENT PREOPERATIVE PREPARATION Premedications

Consider administration of DDAVP either nasally or intravenously, if the clinical condition dictates. INTRAOPERATIVE CARE Choice of Anesthesia

No specific anesthetic choices are indicated aside from usual neuroanesthesia care and concerns. Monitors

• ASA monitors • Additional monitoring should be based upon the patient disease and procedure requirements. An arterial line (or central line) allows for serial monitoring of serum sodium and osmolality. • Foley catheter allows for accurate recording of fluid intake and output, and avoids overdistension of the bladder. Also allows for serial monitoring of urine sodium and specific gravity. Induction/Airway Management

Usual neuroanesthesia induction Maintenance

• Usual neuroanesthesia maintenance and concerns • Fluids: – Monitor ins and outs.

– Hypotonic IV fluids (hypoosmolar relative to the patient’s serum) should be used to match the urine output. – If using dextrose and water as fluid replacement, care must be taken to avoid hyperglycemia; generally, administration should be limited to 500–750 mL/hr and glucose levels should be monitored. – When mannitol or furosemide must be administered to facilitate surgical conditions, it may confuse the picture with respect to fluid losses and replacement. Close monitoring of electrolytes, glucose, and serum osmolality as well as hemodynamic values should be used to aid in fluid replacement, as urine specific gravity may be misleading. • ADH therapy: – Desmopressin 1–2 mcg/kg IV or SQ may be started or continued perioperatively. – Re-dose if urine output remains >200–250 mL/hr for ≥2 hours with a urine specific gravity <1.005 or urine osmolality <200 mOsm/L. • Consider concomitant anterior pituitary insufficiency and the need for stress dose corticosteroids.

Extubation/Emergence

Usual neuroanesthesia concerns

POSTOPERATIVE CARE BED ACUITY

The patient will need a monitored setting to allow for frequent lab checks and possible administration of DDAVP. MEDICATIONS/LAB STUDIES/CONSULTS

• DDAVP • Careful measurement of I/Os, monitor for hypovolemia, especially if the patient is unable to drink fluids freely • Serial serum/urine sodium levels and serum/urine osmolality levels • Endocrinology and neurology consults

COMPLICATIONS

If left untreated, may cause severe hypernatremia and the sequelae associated with this derangement

REFERENCES

1. Nemergut EC, Dumond AS, Barry UT, et al. Perioperative management of patients undergoing transsphenoidal pituitary surgery. Anesth Analg. 2005;101:1170–1181. 2. NIH. Diabetes insipidus. Publication No. 01-4620, December 2000.Saborio P, Tipton GA, Chan JCM. Diabetes insipidus. Peds Rev. 2000;21(4):122–129. 3. Ozier Y, Bellamy L. Pharmacological agents: Antifibrinolytics and desmopressin. Best Pract Res Clin Anaesthesiol. 2010;24:107–110. http://www.diabetesinsipidus.org/whatisdi.htm See Also (Topic, Algorithm, Electronic Media Element)

• Hypernatremia • Syndrome of inappropriate antidiuretic hormone (SIADH) release • Serum osmolality • Urine osmolality

CODES ICD9

253.5 Diabetes insipidus ICD10 E23.2 Diabetes insipidus

CLINICAL PEARLS

• Diabetes insipidus results from a deficiency in ADH secretion or abnormal renal response to ADH. • It manifests as polyuria/polydipsia with low urine osmolarity and hypernatremia. • May present following neurosurgery, especially surgery of the pituitary or hypothalamus • Usually presents within the first 24–48 hours postoperatively and is transient

DIABETES MELLITUS Zhuang-Ting Fang, MD, MSPH

BASICS DESCRIPTION

• Diabetes mellitus (DM) has been increasing in the last several decades, likely due to its strong association with obesity. • DM is one of the leading causes of morbidity and mortality in the US population, with an economic cost of $171 billion annually. EPIDEMIOLOGY Prevalence

In the US: 1.3 million new cases annually Prevalence

In the US: 25.8 million people have the disease, accounting for 8.3% of the population. Morbidity

A risk factor for perioperative surgical and anesthetic complications Mortality

7th leading cause of death in the US ETIOLOGY/RISK FACTORS

• Type I diabetes risk factors: – Genetics and family history – Infection or illness of the pancreas • Type II diabetes risk factors: – Obesity or overweight – Impaired glucose tolerance – Insulin resistance – Hypertension – History of gestational diabetes – Sedentary lifestyle – Family history – Polycystic ovary syndrome – Age – Ethnic background: Diabetes occurs more often in African Americans, Hispanic Americans, Native Americans, Asian Americans, and Pacific Islanders. PHYSIOLOGY/PATHOPHYSIOLOGY

• Normally, blood glucose is tightly regulated by: – The hormonal system which consists of a balance between the hypoglycemic insulin and hyperglycemic counter-regulatory hormones such as glucagon, epinephrine, and cortisol. – Neural mechanisms; glucose sensors in various organs are capable of sending messages. – Together, these systems modulate carbohydrate metabolism by controlling endogenous production and entrance of glucose into the cells. • Type I diabetes is caused by the complete lack of insulin secretion from the pancreas. The inability of cells to take in glucose leads to metabolic abnormalities, including hyperglycemia, lipolysis, proteolysis, and ketogenesis. • Type II diabetes is caused by insulin deficiency or insulin resistance and can result in dehydration and a hyperosmolar state. Type II diabetes patients are usually ketosis-resistant since their insulin concentration in the circulation is sufficient to prevent ketogenesis.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperative fasting, long-acting insulin or oral antihyperglycemics, and surgical stress can result in episodes of hypoglycemia or hyperglycemia. Perioperative glucose testing and treatment should be performed, as appropriate. • Microvascular and macrovascular disease can result in end-organ damage; preoperative evaluation should assess the involvement and severity. Maintain hemodynamic stability to avoid hypoperfusion to the heart, brain, and kidneys. • Consider the possibility of gastroparesis and pulmonary aspiration; if high risk, modify NPO guidelines, premedicate to decrease gastric volume and acidity, and place a cuffed endotracheal tube.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Polyuria, polydipsia, and polyphagia are associated with hyperglycemia and can suggest new-onset diabetes. • Autonomic neuropathy is associated with perioperative hypotension and may be suggested by dizziness and syncope. Impotence is a sign of autonomic nervous dysfunction. • Decrease in vision associated with diabetic retinopathy

History

• Assess metabolic control: Daily glucose level/range, usual dietary intake, physical activity, hemoglobin A1C level, episodes of hypoglycemia or ketoacidosis, and medications. • Assess the severity of concomitant organ dysfunction and optimize as appropriate. A prior myocardial infarction is a clinical predictor for perioperative cardiac events. Hypertension should be checked and controlled prior to surgery. • Gastroparesis manifests as indigestion, nausea, vomiting, diarrhea, and abdominal distension.

Signs/Physical Exam

• Usually nonspecific • Abnormal physical exams are usually related to the complications associated with diabetes.

• “Stiff joint syndrome”: Limited joint mobility may be associated with a potentially difficult tracheal intubation. • Orthostatic hypotension or resting tachycardia associated with autonomic neuropathy

MEDICATIONS

• Exogenous insulin: The types of insulin include rapid-acting (Humalog, Novolog, Apidra), short-acting (Regular, Velosulin), intermediate-acting (NPH, Lente), long-acting (Ultralente, Lantus, Levemir), and pre-mixed (Humulin 70/30, Novolin 70/30, Novolog 70/30, Humulin 55/50, Humalog 75/25). • Oral agents: Sulfonylureas stimulate the pancreas to release more insulin (glipizide, glyburide, glimepiride). Biguanides improve the ability of insulin to move glucose intracellularly (metformin). Thiazolidinediones improve the effectiveness of insulin (pioglitazone, rosiglitazone). Alpha-glucosidase inhibitors block enzymes that digest starch; they slow the rise in blood glucose (acarbose, miglitol). Meglitinides stimulate the pancreas to release more insulin (repaglinide, nateglinide). Dipeptidyl peptidase IV inhibitors increase insulin secretion from the pancreas and decrease glucose production from the liver (sitagliptin, saxagliptin). Combination therapy combines the above-described mechanisms for improved glycemic control (glyburide/metformin; glipizide/metformin; rosiglitazone/metformin). • ACE inhibitors or angiotensin receptor antagonists provide protective effects in diabetes patients with CHF and renal insufficiency in addition to the treatment of hypertension. May be associated with refractory hypotension. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Labs: Glucose, HgA1C, BUN/Cr (renal function), electrolytes • EKG: Silent ischemia or old infarcts • Cardiac stress tests if indicated

CONCOMITANT ORGAN DYSFUNCTION

• Neurologic: Cerebrovascular disease (stroke); peripheral neuropathy from direct mesangial expansion and injury from chronic hyperglycemia • Retinopathy is present in 28.5% of patients aged ≥40 years; it is the leading cause of new cases of blindness in adults aged 20–74 years. • Cardiovascular: Heart disease (comprises 68% of patients ≥65 years who died from diabetes-related complications). Mechanisms are complex and multifactorial and are related to both macrovascular and microvascular dysfunction. Hypertension (67% of diabetics); progression is likely due to activation of the local renin–angiotensin system. • Renal: Leading cause of renal failure (microvascular disease) • Metabolic: Diabetic ketoacidosis (DKA) is the most serious acute metabolic emergency. Hypoglycemia is more common than DKA in IDDM and is dangerous. CIRCUMSTANCES TO DELAY/CONDITIONS

• Severe hypoglycemia or hyperglycemia, especially in patients with symptoms of ketoacidosis or hyperosmolar nonketotic coma

• Acute infections • Severe dehydration or electrolyte imbalance

CLASSIFICATIONS

• Type I diabetes (insulin-dependent) is caused by absolute insulin deficiency secondary to immune-mediated or idiopathic causes. Patients are also prone to ketosis. • Type II diabetes (non-insulin dependent) is usually adult onset and secondary to relative insulin deficiency and resistance.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Oral agents should be withheld on the morning of surgery to avoid perioperative hypoglycemia. Metformin should be withheld for 24 hours; it has been associated with fatal metabolic acidosis. • Night doses of long acting insulin and morning doses are often decreased (or withheld) to avoid hypoglycemia in the fasting patient. • Glucose level should be checked.

INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on the type and duration of surgery, comorbidities, and patient’s preference • Regional anesthesia (spinal, epidural, or peripheral nerve blocks) may modulate the secretion of insulin and catabolic hormones and block the body’s response to surgical stress under general anesthesia. However, it may increase risks of profound hypotension (especially in patients with autonomic neuropathy), infection, and vascular injury. There is some evidence to suggest that local anesthetics are more toxic to peripheral nerves in diabetics, and the standard nerve stimulator utilized for localization may exhibit reduced effectiveness. Monitors

• Standard ASA monitors • Invasive BP (in patients with severe CAD, autonomic neuropathy, and for close monitoring of glucose during prolonged surgery under general anesthesia) Induction/Airway Management

• Consider the possibility of a difficult airway in patients with stiff joint syndrome. • Intravenous induction should be accomplished by careful titration to avoid hypotension. – Benzodiazepines and etomidate may decrease ACTH secretion and block adrenal steroidogenesis, respectively; this can decrease cortisol synthesis. – Propofol may cause profound hypotension in patients with severe autonomic neuropathy. • Rapid-sequence induction with cricoid pressure should be considered in patients with gastroparesis to decrease the risk for pulmonary aspiration.

Maintenance

• For general anesthesia, a “balanced technique” (combination of volatile agents, narcotics, and intravenous anesthetics) is preferable to reduce the potential metabolic disturbance from each individual agent. Volatile agents may impair the insulin response to elevated glucose from the sympathetic stimulation of surgery and general anesthesia. • Total intravenous anesthesia with propofol may result in hypotension. Additionally, there may be a decreased ability to metabolize propofol because of the impaired lipid metabolism in diabetic patients. • Narcotics may have the benefit of hemodynamic stability, as well as stable metabolic and hormonal stages. • Glucose control: Intraoperative monitoring and treatment with IV insulin (or dextrose) should be considered, particularly in brittle diabetics (q 30–60 minutes, with intraoperative insulin either via IV bolus or infusion). Continuous intravascular glucose monitors may aid in tight blood glucose control perioperatively and in critically ill patients. Currently, they are not in common use. • Maintain normothermia; hypothermia can worsen postoperative insulin resistance.

Extubation/Emergence

• Ensure that patients have fully recovered from muscle relaxants or been adequately reversed. Patients should be awake with intact protective gag reflexes prior to extubation. • Prophylaxis for postoperative nausea and vomiting. Metoclopramide may decrease postoperative nausea and vomiting (PONV) by enhancing gastric emptying, especially in patients with gastroparesis.

FOLLOW-UP BED ACUITY

• Vigilant monitoring to detect and treat hypotension, myocardial ischemia, and acute renal failure • In certain circumstances (brittle, high-risk surgery) hourly glucose monitoring (and treatment) may be appropriate. • Close monitoring for respiratory dysfunction, hypothermia, and hypoxia • Avoid oversedation that may delay the identification of mental alteration from hypoglycemia or ketoacidosis

COMPLICATIONS

• Metabolic abnormality (hypoglycemia, hyperglycemia, lactic acidosis) • Myocardial infarction • Perioperative aspiration • Acute renal failure • Infection

REFERENCES

1. American Diabetes Association. Diabetes statistics. 2011.

2. Lena D, Kalfon P, Preiser JC, et al. Glycemic control in the intensive care unit and during the postoperative period. Anesthesiology. 2001;114(2):438–444.

3. McAnulty GR, Robertshaw HJ, Hall GM. Anesthestic management of patients with diabetes mellitus. Br J Anaesth. 2000;85(1):80–90. 4. Rigaud M, Filip P, Lirk P, et al. Guidance of block needle insertion by electrical nerve stimulation: A pilot study of the resulting distribution of injected solution in dogs. Anesthesiology. 2008;109:473–478.

5. Schricker T, Wykes L, Carli F. Epidural blockade improves substrate utilization after surgery. Am J Physiol. 2000;279:E646–E653. 6. Skjaervold NK, Solligard E, Hjelme DR, et al. Continuous measurement of blood glucose: Validation of a new intravascular sensor. Anesthesiology. 2011;114(1):120–125.

See Also (Topic, Algorithm, Electronic Media Element)

• Hypoglycemia • Hyperglycemia • Diabetic ketoacidosis • Hyperosmolar hyperglycemic nonketotic coma • Postoperative renal dysfunction

CODES ICD9 • 250.00 Diabetes mellitus without mention of complication, type II or unspecified type, not stated as uncontrolled • 250.01 Diabetes mellitus without mention of complication, type I [juvenile type], not stated as uncontrolled ICD10 • E10.9 Type 1 diabetes mellitus without complications • E11.9 Type 2 diabetes mellitus without complications

CLINICAL PEARLS

• Patients should be scheduled early, preferably the first case. • Patients with end-organ disease (cerebral, cardiac, renal) may not tolerate hypoxic events or hypotension well.

DIABETIC KETOACIDOSIS Matthew V. Satterly, MD Ori Gottlieb, MD

BASICS DESCRIPTION

• Diabetic ketoacidosis (DKA) is the triad of hyperglycemia, ketonemia, and acidemia. • DKA is generally associated with type 1 diabetes mellitus (DM) but can be associated with type 2 in cases of extreme stress (sepsis, trauma etc.). • It is classified as mild, moderate, or severe based on the pH, serum bicarbonate, and mental status. • DKA is differentiated from hyperglycemic hyperosmolar non-ketotic (HHNK) coma which usually lacks ketones and acidemia and is more common in type 2 diabetes. HHNK is often associated with a higher serum glucose concentration that may exceed 1,000 mg/dL and the serum osmolality may exceed 380 mOsm/kg. EPIDEMIOLOGY Prevalence

• In the US, there were 115,000 hospital discharges for DKA in 2003 • Annual incidence rate for DKA estimated from population-based studies ranges from 4.6 to 8 episodes per 1,000 patients with diabetes. Mortality

Mortality <5% in experienced centers ETIOLOGY/RISK FACTORS

• Most often precipitated by infection or discontinuation of insulin • May also develop from major illness such as myocardial infarction (MI) or cerebrovascular accident (CVA) • Ketoacidosis may also be present with starvation or acute alcohol intoxication.

PHYSIOLOGY/PATHOPHYSIOLOGY

• DKA results from a relative shortage of circulating insulin in the body, resulting in impaired glucose uptake and utilization by peripheral tissues. This can be secondary to: – Actual deficiency (lack of insulin administration) – Increased demand (sepsis or other hypermetabolic state) • Gluconeogenesis: To counter the lack of insulin, and glucose available for cells, the body responds by releasing counter-regulatory hormones (e.g., glucagon, cortisol, catecholamines, growth hormone). • Lipolysis: The body institutes fatty acid oxidation, or lipolysis, to provide tissues with an energy substrate. The byproducts of lipolysis are called ketone bodies.

– B-hydroxybutyrate (technically a carboxylic acid and not a ketone) – Acetoacetate – Acetone: Produced by decarboxylation of acetoacetate • Hypovolemia and electrolyte derangements: Glycosuria leads to an osmotic diuresis that results in: – Dehydration: On average, patients are negative by 5–8 L. – Loss of electrolytes, most notably potassium and sodium. Potassium deficits range from 200–400 mEq due to osmotic diuresis and a chronic catabolic state. However hyperkalemia is often present initially due to the lack of insulin (decreaes K+ intake into the cell via Na+/K+ -ATPase) and metabolic acidosis. Sodium deficits range from 350– 600 mEq due to osmotic diuresis. However the patient often presents initially with a hypovolemic hypernatremia derangement due to water loss in excess of sodium loss. – Anion gap acidosis: Ketone bodies are acids that titrate the body’s buffering bases.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Delay elective procedures: The goal is to correct the inciting factor, re-establish euvolemia, and electrolyte levels as much as possible before going to the operating room. • The indication for emergency surgery may be an inciting factor for DKA; thus, preoperative correction is not always possible. In this case, initiate measures to restore euvolemia and replete electrolytes as the first priority, then correct hyperglycemia. • If possible, in insulin-dependent diabetes, schedule elective cases early in the day to minimize preoperative fasting and lipolysis/ketosis from a lack of insulin.

PREOPERATIVE ASSESSMENT SYMPTOMS Weakness History

• Evaluate diabetes severity, prior episodes of DKA, and comorbidities • Inquire about diabetic medications: Insulin regimen and adherence as well as last dose • Assess for precipitating factors: Sepsis, pancreatitis, MI, CVA, drugs (corticosteroids, thiazides, sympathomimetics)

Signs/Physical Exam

• Polyuria • Polydipsia • Weight loss • Vomiting • Abdominal pain • Dehydration • Distinct breath odor—described as “fruity” due to presence of expired acetone • Tachypnea early followed by deep labored breathing (Kussmaul respirations) as the acidosis worsens

• Altered mental status • Shock • Coma • Volume status: Skin turgor, dry mucus membranes

TREATMENT HISTORY

• Volume resuscitation • Electrolyte replacement • Acute coronary syndrome therapy if precipitating event is cardiac ischemia or infarction • Stroke treatment if precipitating event is cerebrovascular

MEDICATIONS

• Insulin • Antibiotics if precipitating event is sepsis or infection • Sodium bicarbonate

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Serum glucose • HgA1C: Poor control may suggest the presence of diabetes-related comorbidities. • Ketonuria: Presence of β-hydroxybutyrate, acetoacetate, and/or acetone in the urine. Measured with urine dipstick: – Small amount <20 mg/dL – Large amount >80 mg/dL • Electrolyte: Hyperchloremic anion gap acidosis: AG = [Na+] – ([Cl−] + [HCO3−]) • BUN and serum creatinine • ABG (pH) • Serum osmolality • CBC: Leukocytosis may be related to ketoacidosis, not necessarily infection. • Amylase: May be elevated due to a nonpancreatic source in DKA

CONCOMITANT ORGAN DYSFUNCTION

• Neuropathy: Autonomic nervous system dysfunction may result in difficulties with regulating blood pressure and temperature. • Cardiovascular disease: Perioperative morbidity and mortality with DM often results from cardiac causes. • Nonenzymatic glycosylation and formation of abnormal proteins may result in decreased elastance and thus difficult intubation. • Gastroparesis: Many consider patients with DM as a “full stomach” despite NPO status. • Renal insufficiency

CIRCUMSTANCES TO DELAY/CONDITIONS

Delay elective procedures: The goal is to correct the inciting factor, re-establish euvolemia and electrolyte levels as much as possible before going to the operating room.

See Table

TREATMENT PREOPERATIVE PREPARATION Premedications

In emergent surgeries, intensive therapy with volume resuscitation, insulin infusion, and electrolyte replacement should be continued en route to the operating room. Special Concerns for Informed Consent

• Disoriented or intubated patients cannot be consented. • Family members should be advised about the severity of their condition, emergent nature of the surgery, and the increased risk of mortality. INTRAOPERATIVE CARE Choice of Anesthesia

Guided primarily by the procedure except in cases of altered mental status when intubation is required for airway protection Monitors

• Standard ASA monitors • Arterial line may be useful for frequent lab checks as well as to monitor beat-to-beat blood pressure in patients who are hypovolemic or in septic shock. • Foley catheter: Ins and outs should be carefully monitored. • Central line access may be useful to guide fluid administration.

Induction/Airway Management

• Consider rapid-sequence induction/intubation if a full stomach is suspected or there is risk for aspiration. • Patients are hypovolemic and may become unstable with induction medications. Consider etomidate and/or ketamine if appropriate. • Induction agents may have effects on glucose homeostasis but are clinically insignificant.

Maintenance

• Intensive care therapy should be continued in the operating room in the same manner. • Labs: – Blood glucose ∼ hourly – pH – Electrolytes (potassium) – Intraoperative monitoring of β-hydroxybutyrate may help trend the response to therapy and indicate resolution. • Volume resuscitation: – 0.9% NaCl: 15–20 mL/kg for the first hour – 0.45% NaCl: 4–14 mL/kg/hr if serum sodium is within or elevated above normal values

(institution-based). – D5 0.45% NaCl should be started when the serum glucose level is <200 mg/dL. – Lactated Ringers (LR) may also be used and may be preferable given its pH (or effect on pH). It should also be noted that LR contains 4 mEq/L of potassium. – Fluid replacement alone may drop the serum glucose level ∼50 mg/dL/hr. – Adjust accordingly for cardiac and renal pathology – Resuscitation should also factor in insensible and surgical blood loss. – If packed red blood cells are administered, the use of washed cells may be beneficial as acid citrate dextrose may worsen hyperglycemia. • Insulin therapy: – Regular insulin: 0.1–0.2 U/kg initial IV bolus – Insulin infusion: 0.1 U/kg/hr, with the goal of decreasing serum glucose by 50–75 mg/dL/hr. If glucose does not decrease as expected, consider doubling the infusion rate. – Continue infusion until serum glucose <200 mg/dL then reduce infusion to 0.02–0.05 mg/kg/hr and consider changing to SC management. • Potassium replacement: – If [K+] <3.3 mEq/L hold insulin and replete potassium – If [K+] >5.3 mEq/L continue insulin and monitor every 2 hours – If [K+] = 3.3–5.3 mEq/L continue to administer 20–30 mEq in each liter of fluids • Sodium bicarbonate: Controversial and is usually not indicated; may be considered in cases of refractory acidosis (serum pH <7.15 and [HCO3−] <10 mEq/L) • Normothermia: Hypothermia decreases the response to insulin.

Extubation/Emergence

Emergence/extubation should be based on mental status, volume status, and hemodynamic stability.

FOLLOW-UP BED ACUITY

• ICU admission is usually required as patients may have altered mental status, hypovolemia, or require vasopressors or an insulin infusion. • Telemetry or floor bed may be considered if there is resolution of DKA as demonstrated by a closing of the anion gap (<12), serum glucose <200 mg/dL, sodium bicarbonate level ≥18 mEq/L, and pH >7.3.

MEDICATIONS/LAB STUDIES/CONSULTS

• Endocrine consult may be advantageous. • Frequent blood glucose checks • Electrolyte monitoring: Potassium moves intracellularly as the acidosis is corrected. • Ketonemia and ketonuria may persist for 1–2 days with proper correction of acidemia. • Once DKA has resolved and the patient is eating, consider resuming the patient’s preoperative insulin regimen or initiating new therapy with short/long- acting agents as

necessary.

COMPLICATIONS

• Hypoglycemia may result from excess insulin therapy. • Overly aggressive fluid resuscitation may lead to pulmonary edema and/or congestive heart failure. • Continued shock may occur if inadequate resuscitation is performed. • Over-repletion of electrolytes (potassium) may lead to cardiac arrhythmia. • Central pontine myelinolysis may result from correction of hyponatremia at a rate >10–12 mEq/hr over the first 24 hours.

REFERENCES

1. Hirsch I, McGill JB, Cryer PE, et al. Perioperative management of surgical patients with diabetes mellitus. Anesthesiology. 1991;74:346–359. 2. Kitabchi A, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2006;29(12):2739–2748. 3. McAnulty G, Robertshaw HJ, Hall GM. Anaesthetic management of patients with diabetes mellitus. Br J Anaesth. 2000;85(1):80–90. 4. Milaskiewicz R, Hall GM. Diabetes and anaesthesia: The past decade. Br J Anaesth. 1992;68:198–206. See Also (Topic, Algorithm, Electronic Media Element)

• Diabetes mellitus • Metabolic acidosis • Hypokalemia • Hyperglycemic hyperosmolar nonketotic coma

CODES ICD9 • 250.10 Diabetes with ketoacidosis, type II or unspecified type, not stated as uncontrolled • 250.11 Diabetes with ketoacidosis, type I [juvenile type], not stated as uncontrolled • 250.13 Diabetes with ketoacidosis, type I [juvenile type], uncontrolled ICD10 • E13.10 Oth diabetes mellitus with ketoacidosis without coma • E10.10 Type 1 diabetes mellitus with ketoacidosis without coma

CLINICAL PEARLS

• Triad of hyperglycemia, ketonemia, and acidemia • Hypovolemia and hyperosmolarity may be life-threatening; thus, volume resuscitation is the first priority.

• Etiology of DKA should be determined and treated. • Preoperative evaluation should include chronic complications related to untreated diabetes as these may have grave perioperative implications. • Preoperative and intraoperative goal should be to mimic normal metabolism and achieve euvolemia, normal blood glucose, pH and serum potassium, and other electrolytes through gradual correction and careful titration with frequent monitoring.

DIASTOLE

Korrin Scott, MD Keith E. Littlewood, MD

BASICS DESCRIPTION

• Diastole describes cardiac chamber relaxation and filling with blood; it is followed by systole, a period of contraction. • Ventricular diastole encompasses more than half the time of the cardiac cycle and consists of 4 phases: – Isovolumic relaxation – Rapid early filling – Diastasis – Atrial contraction PHYSIOLOGY PRINCIPLES

• Active relaxation at the molecular level: – At the cellular level, diastole starts when ATP is hydrolyzed and actin–myosin crossbridges unlink. – This is associated with decreases in cytoplasmic calcium and dissociation of calcium from troponin. – Calcium sequestration into the SR is accomplished by 2 energy-consuming receptors: The calcium adenosine triphosphate pump (SERCA-2) and sodium–calcium exchanger. – The sarcomere rapidly returns to resting length under normal circumstances. However, when energy supplies are diminished, the inability to sequester calcium can impair relaxation. • Valves, volume, and pressure during the 4 stages of diastole: – Isovolumic relaxation time (IVRT): Valves: Tricuspid/pulmonic on the right side of the heart and the mitral/aortic on the left side of the heart are closed. Of note, the electro- mechanical onset of diastole (beginning of relaxation) occurs even while the ventricle is ejecting blood (aortic valve open). When the ventricular pressures drop below the aortic pressures, the aortic valve closes and IVRT begins. Ventricular volume: No change Ventricular pressure: Decreases exponentially – Rapid early filling: Valves: Begins when the tricuspid on the right and the mitral valve on the left open Ventricular volume: Accounts for the majority of ventricular filling (up to 80% of the total stroke volume) Ventricular pressure: Initially, there is little to no change with filling. Patients with decreased compliance (e.g., fibrosis, ischemia, diastolic dysfunction) will have a greater

increase for a given volume (may also impair this passive filling process). – Diastasis: Phase can disappear during tachycardia. Valves: Tricuspid and mitral valves remain open; aortic and pulmonic valves are closed. Ventricle volume: Remains approximately the same as at the end of the rapid early filling phase Ventricle pressure: Atrial and ventricular pressures equalize – Atrial contraction: Valves: Tricuspid and mitral valve open Ventricle volume: The contribution of the “atrial kick” accounts for 15–25% of the stroke volume. Ventricle pressure: Creates a positive pressure gradient across the tricuspid and mitral valve • Pressure–volume loops can aid with the assessment of viscoelastic properties of the ventricle. As described above, during passive filling, the slope is relatively flat; it begins to increase as the ventricle fills.

ANATOMY

The heart consists of 2 atria and 2 ventricles that circulate blood in series. • The right and left ventricles differ in their shape and size, as well as the pressure against which they contract (afterload). • Right ventricle: Pumps through the low-resistance pulmonary circulation. It is crescentshaped with an inflow and outflow region that contract sequentially to eject blood into the low-pressure pulmonary circulation. • Left ventricle: Pumps through the systemic circulation. It is ellipsoidal in shape with the muscle fibers arranged longitudinally in the subepicardium and subendocardial layers, and circumferentially in between these 2 layers. The LV ejects blood with a corkscrew type of motion with the apex moving towards the base. Wall motion of regions supplied by branches of the coronary artery can be individually assessed semi-quantitatively by echocardiography. DISEASE/PATHOPHYSIOLOGY

• Factors that can affect the passive pressure–volume properties: – LV chamber volume: Increases in preload (LV end diastolic volume) from volume overload or decreased forward flow move the pressure–volume curve rightwards. This results in smaller changes in volume will have a large change in pressure (steeper slope). – Composition of the LV wall (endocardium and myocardium): Hypertrophy of muscle, postischemic scarring, fibrosis, edema, amyloid deposition, and hemosiderin can “stiffen” the wall and decrease compliance. – Extrinsic factors on the ventricle: Pericardial disease, overdistention of the contralateral ventricle, increased airway or pleural pressure, tumors, and surgical compression can decrease LV compliance. – Distensibility/elasticity: Active elasticity of the LV wall is a function of residual crossbridge activation and sarcomere contraction. This potential energy acts as a recoiling force that restores the myocardium to its resting configuration. • Diastolic heart failure (DHF)

– Definitions ACC/AHA criteria: Typical signs and symptoms of heart failure; normal LV ejection fraction (>50%); failure not explained by valvular abnormality The European Society of Cardiology. Includes additional criteria of evidence of dysfunction through invasive measurements (LVEDP, PCWP >16 mm Hg) or echocardiogram parameters. – Mechanism is multifactorial and poorly understood. It can result from either: Intrinsic: Factors affecting ventricular muscle including myocardial relaxation and coronary turgor Intrinsic factors affecting external compression of the LV including RV pressure or volume overload, pericardial disease, pleural and mediastinal pressure, and atrial contraction – Linking etiology with cellular mechanisms Aging is associated with prolonged isovolumic relaxation and altered calcium homeostasis as well as interstitial fibrosis and increased cross-linking of collagen that can cause LV stiffness. Chronic hypertension increases myocardial work/tension and is often compensated for with muscle hypertrophy. Diabetes is associated with myocyte hypertrophy and interstitial fibrosis with microvascular disease. • Atrial kick: The stroke volume decreases in the absence of an atrial contraction; this can be seen with atrial fibrillation, atrial flutter, low atrial rhythms, or junctional rhythms. In patients with decreased ventricular compliance, where passive filling is already decreased, the stroke volume becomes more dependent on the atrial “kick.”

PERIOPERATIVE RELEVANCE

• Echocardiogram: LV diastolic function is assessed via pulse wave Doppler (PWD) assessment through the mitral valve. A mid-esophageal 4-chamber view allows the beam to be aligned parallel to blood flow and thus provides the most ideal imaging of flow and velocity. The transmitral pattern is composed of the: – “E” wave: Represents the rapid filling phase – “A” wave: Represents atrial contraction. The wave is approximately 1/3} to 1/2 the size of the E wave. – Deceleration time (DT): Time it takes for the E wave velocity to become zero. A time <220 ms represents good LV relaxation and a rapid decline in ventricular pressure. • PWD classification of diastolic dysfunction – Impaired relaxation (Grade I): This initial pattern of dysfunction is seen early in the course of hypertension, myocardial ischemia, and hypertrophic cardiomyopathy. Small “E” wave Large “A” wave E/A ratio <1 Prolonged DT (>240 ms) – Pseudo-normal pattern (Grade II): As the disease process progresses, the LA pressure and, hence, LA–LV gradient increases. This results in a “normal” appearing pattern. In order to distinguish true normal from pseudonormal, maneuvers to decrease preload (e.g.,

Valsalva, nitroglycerin, etc.) can be applied to unmask a small “E” wave, large “A” wave, and prolonged DT time. Normal appearing “E” wave: The increased size compared to Grade I reflects the increase in passive filling flow from the increased LA–LV gradient. Normal appearing “A” wave: The decreased size compared to Grade I reflects the minimal contribution of the atrial contraction. E/A ratio >1 DT of 160–240 ms: The shortened time results from rapid equilibration pressure between the LA and LV. – Restrictive pattern (Grade III and IV) can be seen in decompensated heart failure, severe coronary artery disease, constrictive pericarditis, and severe aortic and mitral insufficiency. They result in LV filling occurring primarily in early diastole. Very large “E” wave Small “A” wave E/A ratio >2 Shortened DT interval from rapid rise in the LV diastolic pressure and time to diastasis

EQUATIONS

Laplace’s law: T = (P × r)/(2 × h), where P is the intraventricular pressure, r is the ventricular radius, and h is wall thickness.

GRAPHS/FIGURES

FIGURE 1. The 4 phases of diastole. IVRT begins with aortic valve closure and ends with mitral valve opening. RFP— Rapid Early Filling. MVF—Mitral Valve Flow.

FIGURE 2. Doppler E and A waves from echocardiogram are superimposed. (Reproduced from Reference 3, permission requested and pending).

REFERENCES

1. Alsaddique AA, Royse AG, Royse CF, et al. Management of diastolic heart failure following cardiac surgery. Eur J Cardiothorac Surg. 2009;35(2):241–249. 2. Daneshvar D, Wei J, Tolstrup K, et al. Diastolic dysfunction: Improved understanding using emerging imaging techniques. Am Heart J. 2010;160(3):394–404. 3. Hoit B. Left ventricular diastolic function. Crit Care Med. 2007;35(Suppl 8):S340–S347. 4. Mahmood F, Matyal R. Assessment of perioperative diastolic function and dysfunction. Int Anesthesiol Clin. 2008;46(2):51–62. 5. Ouzounian M, Lee DS, Liu PP. Diastolic heart failure: Mechanisms and controversies. Nat Clin Pract. 2008;5(7):375–386. 6. Pagel PS, Grossman W, Haering JM, et al. Left ventricular diastolic function in the normal and diseased heart. Anesthesiology. 1993;79(5):1104–1120. 7. Satpathy C, Mishra TK, Satpathy R, et al. Diagnosis and management of diastolic dysfunction and heart failure. Am Fam Physician. 2006;73(5):841–846.

ADDITIONAL READING

• Mahmood F, Matyal R, Subramaniam B, et al. Transmitral flow propagation velocity and assessment of diastolic function during abdominal aortic aneurysm repair. J Cardiothorac Vasc Anesth. 2007;21(4):486–491. • Skubas N. Intraoperative Doppler tissue imaging is a valuable addition to cardiac anesthesiologists’ armamentarium: A core review. Anesth Analg. 2009;108(1):48–66.

See Also (Topic, Algorithm, Electronic Media Element) • Atrial fibrillation • Systole • Pressure–volume loops

• Lusitropy

CLINICAL PEARLS

• Lusitropy (early diastolic relaxation) is an active, ATP-dependent process. • Diastolic dysfunction is often asymptomatic, and when symptoms are present, it is often difficult to distinguish from systolic failure. Echocardiogram can provide a noninvasive method to categorize the type of heart failure. • LV end-diastolic pressure can be used as a measure of preload only if the relationship between ventricular volume and pressure (ventricular compliance) is constant. • Patients with reduced ventricular compliance are most affected by the loss of a normally timed atrial systole (loss of atrial kick).

DIBUCAINE NUMBER Benjamin Abraham, MD

BASICS DESCRIPTION

• The dibucaine number (DN) is a laboratory test that indirectly determines the presence of an atypical genetic variant of pseudocholinesterase. – It is a qualitative (not quantitative) assessment of enzyme function. • The duration of succinylcholine and mivacurium activity, and hence neuromuscular blockade, is dependent on both the catalytic ability/activity (qualitative) and levels of pseudocholinesterase (quantitative). PHYSIOLOGY PRINCIPLES

• Pseudocholinesterase is responsible for the hydrolysis of succinylcholine to succinylmonocholine and choline, and hence termination of the drug’s activity. Pseudocholinesterase (1): – Is produced by the liver – Is encoded by a gene on Chromosome 3 – Circulates in the plasma with a half-life of approximately 8–16 hours – Is also known as butyrylcholinesterase or plasma cholinesterase • Pseudocholinesterase variants (qualitative abnormality): Homozygous typical pseudocholinesterase is most commonly found in the population. However, there is a small subset of patients who possess an atypical variant of the gene, and will have prolonged neuromuscular blockade when succinylcholine is administered (2). – Heterozygous atypical: One abnormal gene – Homozygous atypical: Both genes are abnormal – Other gene variants exist, but are rare • Decreased pseudocholinesterase levels (quantitative abnormality) (3,4) – Liver disease: Even when plasma cholinesterase activity was reduced by 80% (in severe liver disease), apnea duration was found to be approximately 9–15 minutes. – Pregnancy: No clinically significant prolongation of action is seen. – Malnutrition • Dibucaine number (DN) (3) – Dibucaine is a local anesthetic that was found to inhibit: Typical pseudocholinesterase genotype activity by 70–80% Heterozygous typical genotype activity by 50–60% Homozygous atypical genotype activity by <30% – The amount of inhibition is known as the dibucaine number. • Dibucaine testing (3) – DN = [1 – (pseudocholinesterase activity in the presence of inhibitor/pseudocholinesterase activity in the absence of inhibitor)] × 100

– Measuring pseudocholinesterase activity in the absence of an inhibitor is as follows: The substrate acetylthiocholine is added to the patient’s serum and is cleaved by pseudocholinesterase to form acetate and thiocholine. Thiocholine reacts with Ellman’s reagent (dithiobis-nitrobenzoic acid) to form 5-mercapto-2-nitrobenzoic acid. The amount of absorption at specific wavelengths of light is proportional to the amount of 5-mercapto2-nitrobenzoic acid, and therefore proportional to the % activity of pseudocholinesterase. – Pseudocholinesterase activity in the presence of dibucaine (inhibitor) is measured as follows: A specified concentration of dibucaine is added to the patient’s serum, followed by the addition of acetylthiocholine and Ellman’s agent. Light absorption is measured (proportional to 5-mercapto-2-nitrobenzoic acid) to determine the % activity of pseudocholinesterase. • Quantitative measures: It is important to remember that the DN is not a quantitative test of the amount of enzyme in the serum, but rather a test of its function.

ANATOMY

• Within the neuromuscular junction (NMJ), acetylcholine neurotransmitter is metabolized by acetylcholinesterase (reuptake by the presynaptic membrane also occurs). • Pseudocholinesterase circulates in the plasma. Therefore, termination of succinylcholine’s activity requires diffusion away from the NMJ and into the plasma, where it is then metabolized by pseudocholinesterase.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Heterozygous atypical • Usually clinically insignificant; with blockade being prolonged on the order of seconds or minutes, if at all. • DN = 50–60% • Found in approximately 1:25 Caucasians • Homozygous atypical • The duration of blockade can persist for 4–8 hours (5). • DN = ≤30% • Found in approximately 1:2,500 Caucasians • Atypical genotypes are rarely seen in Asians and African blacks.

PERIOPERATIVE RELEVANCE

• Succinylcholine is a depolarizing muscle relaxant with a rapid onset and short duration of action. It provides profound relaxation and excellent intubating conditions, and is most commonly used today for rapid-sequence intubation (RSI). • With the advent of newer, intermediate- and short-acting non-depolarizing agents, succinylcholine is used less frequently now as an infusion • Following administration, approximately 90–95% of succinylcholine is hydrolyzed and inactivated by pseudocholinesterase prior to reaching the NMJ. Thus, variants of pseudocholinesterase result in higher levels reaching the NMJ as well as decreased metabolism once they diffuse away from the junction. • Prolonged apnea following succinylcholine administration requires supportive measures such as the institution, or continued application, of mechanical ventilation. Other causes for

ventilatory failure should be ruled out (hypothermia, hypercarbia, CNS injury, etc.) while further testing is undertaken.

EQUATIONS

DN = [1 – (pseudocholinesterase activity in the presence of inhibitor/pseudocholinesterase activity in the absence of inhibitor)] × 100

REFERENCES

1. arnas ML, Procter M, Schwarz MA, et al. Concordance of butyrylcholinesterase phenotype with genotype: Implications for biochemical reporting. Am J Clin Pathol. 2011;135(2):271–276. 2. Pantuck EJ. Plasma cholinesterase: Gene and variations. Anesth Analg. 1993;77(2):380– 386. 3. Elamin B. Dibucaine inhibition of serum cholinesterase. J Biochem Mol Biol. 2003;36(2):149–153. Green DW, Fisher M, Sockalingham I. Mivacurium compared with succinylcholine in children with liver disease. Br J Anaesth. 1998;81(3):463–465. 4. Viby-Mogensen J. Correlation of succinylcholine duration of action with plasma cholinesterase activity in subjects with the genotypically normal enzyme. Anesthesiology. 1980;53(6):517–520.

ADDITIONAL READING

• Jensen FS. Plasma cholinesterase and abnormal reaction to succinylcholine: Twenty years’ experience with the Danish Cholinesterase Research Unit. Acta Anaesthesiol Scand. 1995;39(2):150–156.

See Also (Topic, Algorithm, Electronic Media Element) • Intubation and extubation criteria

CLINICAL PEARLS

• Succinylcholine should be avoided, if possible, in any patient with a known history of atypical pseudocholinesterase. • If prolonged apnea following succinylcholine administration occurs, supportive measures such as mechanical ventilation should be continued, while other causes for apnea are ruled out. Heterologous blood transfusion has been used in rare instances when rapid reversal of the blockade was required. However, this technique must carefully weigh the risks versus the benefits. • Many patients remain unaware of the presence of an abnormal pseudocholinesterase genotype. This mutation is often only discovered after the patient (or a relative) develops prolonged neuromuscular blockade after intubation, since the disorder has no other known physiologic manifestations. • Neostigmine and organophosphate pesticides act as potent inhibitors of pseudocholinesterase. Patients who are given neostigmine to reverse non-depolarizing

blockade, and are subsequently re-intubated using succinylcholine, will experience a prolonged blockade. • While the varied terminology is somewhat confusing, pseudocholinesterase, butyrylcholinesterase, and plasma cholinesterase are all synonymous. • Nonspecific plasma esterases, such as those involved in the degradation of atracurium or remifentanil, are different entities entirely. • Acetylcholinesterase (also known as “true cholinesterase”) is found at the NMJ, and is responsible for the hydrolysis of acetylcholine.

DIFFICULT AIRWAY Jennifer Wu, MD, MBA

BASICS DESCRIPTION

• Aspects of airway management that may prove to be difficult include: – Ventilation – Laryngoscopy – Endotracheal tube placement – Laryngeal mask airway (LMA) placement • The most dangerous situation in airway management is the “cannot ventilate, cannot intubate” scenario. • Airway evaluation is important in predicting a difficult airway; most difficult or emergent airways are associated with preoperative anatomic or pathologic risk factors. • The ASA American Society of Anesthesiologists (ASA) Difficult Airway Algorithm provides a useful approach to difficult airway management in the event that laryngoscopy or ventilation becomes impossible (1). • Skilled help, alternative airway tools, and surgical airway equipment may be necessary to secure the airway. EPIDEMIOLOGY Prevalence

Difficult mask ventilation occurs in 5% of the adult population. Morbidity

Most adverse outcomes relating to airway management occur at the time of induction. Mortality

30% of deaths attributed to anesthesia involve airway management. ETIOLOGY/RISK FACTORS

• Components of the airway evaluation that are associated with a difficult laryngoscopy include the following (2,3): – Mallampati score >2 – Thyromental distance <6 cm – Mouth opening <4 cm – Limited neck mobility – Neck circumference >45 cm – Abnormal upper teeth – Obstructive sleep apnea – Large tongue

• A history of difficult intubation makes repeat intubation very likely to be difficult. • Pathologic processes: – Distortion of the airway (submandibular abscess, anaphylaxis) may make visualization of the vocal cords difficult or impossible – Hoarseness may indicate a vocal cord lesion – The inability to breathe while lying flat may be the result of mass compression on the trachea or a bronchus, which could make ventilation difficult or impossible while under anesthesia • Anatomic defects found in some congenital syndromes are associated with a difficult airway. The conditions most characteristically associated with difficult airway management include Pierre Robin Syndrome, Treacher Collins Syndrome, Menkes Disease, and acromegaly. – Patients with Pierre Robin Syndrome have mandibular hypoplasia, micrognathia, cleft palate, and glossoptosis. Patients will occasionally have a cleft uvula, macroglossia, or laryngomalacia. – Treacher Collins Syndrome is associated with hypoplasia of the maxilla and mandible, micrognathia, and cleft palate. Airway management becomes more challenging as the patient ages. – Menkes Disease is a copper metabolism disease that results in micrognathia, poor bone strength, and easily damaged teeth. – Acromegaly is caused by excessive growth hormone, resulting in characteristic facies, macroglossia, prognathism, and hypertrophy of laryngeal soft tissue, the epiglottis, and the aryepiglottic folds. • External devices may make positioning for direct laryngoscopy difficult or impossible. The halo device is not only associated with difficult laryngoscopy, but also hinders LMA placement and seating.

Pregnancy Considerations

Pregnancy is associated with oropharyngeal edema, engorgement of vessels making bleeding more likely, a full stomach, and large breasts impeding direct laryngoscopy. PHYSIOLOGY/PATHOPHYSIOLOGY

• In an anesthetized patient, oropharyngeal muscle tone is lost and the soft palate, epiglottis, and tongue can obstruct the airway. Positioning and the use of oropharyngeal or nasopharyngeal airways may assist in adequate mask ventilation of the anesthetized patient. • For direct visualization of the vocal cords to be possible, the tracheal and pharyngeal axes must be in-line. This is most often accomplished by placing the patient’s head in the “sniffing position,” a combination of flexion of the neck (usually accomplished by elevating the head) and extension of the head. • Care should be taken when positioning the obese patient. The use of a special ramp-shaped pillow or series of stacked sheets will bring the tracheal and pharyngeal axes in line. External landmarks that aid in this process are the external auditory meatus and sternum, which should be in a straight line parallel with the ground.

PREVENTATIVE MEASURES

• To create an appropriate airway management plan, one must perform a detailed history,

including prior difficult intubation, hoarseness, breathing difficulty, and obstructive sleep apnea. A thorough airway evaluation, including examination of relevant anatomy, will aid in the prediction of a difficult airway. • When a difficult airway is suspected, alternative airway tools and skilled assistants should be made readily available. • When adequate ventilation seems unlikely, an awake intubation with maintenance of spontaneous ventilation should be performed. • Awake intubation may be via the nasal or oral routes. It involves patient cooperation and local anesthesia of the airway, with or without intravenous sedation.

PREOPERATIVE ASSESSMENT • A successful intubation is typically characterized by vocal cord visualization on laryngoscopy, a view of the endotracheal tube passing through the cords, condensation in the tube, bilateral breath sounds on auscultation, and confirmed end-tidal carbon dioxide. When the vocal cords are not visualized and the usual methods to confirm endotracheal intubation are not positive, the intubation is unsuccessful. A change in patient position or use of an alternative laryngoscopy blade may facilitate a repeat attempt at intubation. However, excessive repetitive attempts at laryngoscopy should be avoided to minimize airway trauma and edema. • When intubation fails, consider calling for help. Determine whether mask ventilation is possible by visualizing chest rise, end-tidal carbon dioxide, bilateral breath sounds, and maintenance of oxygen saturation. • If mask ventilation is adequate, continue on the non-emergency pathway of the ASA Difficult Airway Algorithm. Alternative airway equipment can be used to reattempt intubation. If intubation proves to be impossible, the patient can be awakened or a surgical airway can be performed. • If mask ventilation is impossible after failure to intubate, call for help and insert an LMA. If the LMA provides adequate ventilation, continue on the non-emergency pathway. If ventilation is still inadequate, follow the emergency pathway. This is a “cannot intubate, cannot ventilate” scenario. • When a “cannot intubate, cannot ventilate” situation arises, call for help. Attempt emergency noninvasive methods of ventilation, including transtracheal jet ventilation, Combitube, or rigid bronchoscope. If these methods are unsuccessful, perform a cricothyroidotomy or tracheostomy (4).

DIFFERENTIAL DIAGNOSIS

• The absence of bilateral breath sounds could be caused by an esophageal intubation, pneumothorax, foreign body in the trachea or bronchus, large body habitus impeding auscultation, or mainstem intubation. • The absence of end-tidal carbon dioxide could be caused by esophageal intubation, low cardiac output, severe bronchospasm, kinking or dislodgement of the end-tidal carbon dioxide line, or machine failure.

TREATMENT • Optimize patient positioning with a shoulder roll or stacked sheets. • Attempt direct visualization with different blades. The Macintosh blade is useful for patients with an anterior airway. Because the Macintosh blade indirectly lifts the epiglottis and the Miller blade directly lifts it, the Miller blade is optimal for patients with a large epiglottis. • Supraglottic devices – The LMA is a supraglottic device that is inserted blindly. It is useful to facilitate ventilation in a “cannot ventilate, cannot intubate” situation. Many LMAs can also facilitate tracheal intubation (aperture is positioned over the glottic opening) via fiberoptic techniques (see below). – The Combitube is a double-lumen device that is inserted blindly into the trachea or esophagus, and can ventilate the trachea based on which balloon is inflated and which lumen is used for ventilation. • Fiberoptic bronchoscopy (FOB) – Awake FOB: The known or suspected difficult airway can be secured by performing an awake fiberoptic intubation. Spontaneous ventilation is maintained and topical anesthesia is applied to the oropharynx, hypopharynx, and larynx to blunt the response to airway instrumentation. – Asleep FOB: In patients where ventilation appears feasible, an asleep approach can be utilized. – The LMA-Aintree technique begins with insertion of the LMA and confirmation of ventilation. An Aintree Intubation Catheter (AIC) is fiberoptically guided through the LMA into the trachea. The LMA and fiberoptic scope are removed while the AIC is left in place. The endotracheal tube is passed over the AIC and the AIC is removed. • Bougie catheter: If the vocal cords are not visualized, a Bougie catheter may be placed into the trachea with laryngoscopy guidance or blindly. The tracheal rings can be felt and the endotracheal tube is then passed over the Bougie. • Video laryngoscopes include the CMAC and GlideScope. These devices provide a view of the vocal cords that may not be possible with direct laryngoscopy, especially in the anterior airway. • Surgical airway – A cricothyroidotomy can be performed by an experienced provider in less than a minute. It can provide a stable airway for 24 hours before being converted to a tracheostomy. – A tracheostomy is a surgical airway that takes longer to perform as compared with a cricothyroidotomy. Given its more inferior position, risks include damage to the recurrent laryngeal nerves, nearby vascular structures, and the thyroid gland.

FOLLOW-UP • When a difficult intubation occurs, inform the patient in writing. Emphasize the importance of alerting the surgical and anesthesia teams for future procedures. • Document the details regarding the airway and how it was secured and maintain this information in the patient’s medical record.

CLOSED CLAIMS DATA

• The time periods 1985–1992 and 1993–1999 were most recently compared. Death/brain death occurred most often at the time of induction, but there was a decrease in the incidence at induction during the later time period. This improvement is likely a result of widespread adoption of the 1993 Difficult Airway Guidelines (5). • Claims during maintenance, extubation, and recovery remained the same for both time periods. • The odds of death/brain death increased with airway emergency and multiple attempts at laryngoscopy. • A delay in alternative emergency airway management or surgical airway placement led to worse outcomes. • Since 1993, the airway guidelines were used in 8% of cases to defend anesthetic care and in 3% of cases to criticize care.

REFERENCES

1. American Society of Anesthesiologists. Practice guidelines for management of the difficult airway: An updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology. 2003;98(5):1269–1277. 2. Langeron O, Masso E, Huraux C, et al. Prediction of difficult mask ventilation. Anesthesiology. 2000;92(5):1229–1236. 3. Ezri T, Gewurtz G, Sessler D, et al. Prediction of difficult laryngoscopy in obese patients by ultrasound quantification of anterior neck soft tissue. Anaesthesia. 2003;58(11):1111– 1114. 4. Benumof JL, Scheller MS. The importance of transtracheal jet ventilation in the management of the difficult airway. Anesthesiology. 1989;71(5):769–778. 5. Peterson GN, Domino KB, Caplan RA, et al. Management of the difficult airway: A closed claims analysis. Anesthesiology. 2005;103(1):33–39.

ADDITIONAL READING

• ASA Difficult Airway Algorithm

See Also (Topic, Algorithm, Electronic Media Element) • Acromegaly • Jet ventilation • Tracheostomy • Cricothyrotomy • Laryngeal mask airway • Laryngoscopy positioning

CLINICAL PEARLS

• A thorough history and physical exam prior to induction will help the anesthesia care team plan an appropriate airway management strategy.

• When an airway cannot be easily secured, call for help early and follow the ASA Difficult Airway Algorithm. Avoid repetitive intubation attempts, which may cause airway trauma.

DIFFICULT PERIPHERAL INTRAVENOUS ACCESS Bradley A. Stone, MD

BASICS DESCRIPTION

• Intravenous (IV) access is required for: – Venous blood testing – Contrast enhanced imaging – Fluid resuscitation – Medication administration – Blood product transfusion – Short-term parenteral nutrition • IV access is considered difficult if it requires: – Multiple attempts – Staff with unique expertise (IV team, anesthesia department, transport team) – Enhanced vein visualization technology EPIDEMIOLOGY Prevalence

5% of the general population Morbidity

• Phlebitis: – Mechanical – Infectious – Chemical • Infiltration (non-vesicant) • Extravasation (vesicant medication) • Thrombosis • Nerve injury • Hematoma • Compartment syndrome • Unrecognized intra-arterial placement • Pain • Anxiety • Low patient satisfaction

Mortality

In hypovolemic shock or when life-saving medications are urgently needed, the failure to establish a peripheral IV can become life-threatening. ETIOLOGY/RISK FACTORS

• Veins difficult to visualize: – Obesity – Dark skin – Skin disease • Small veins: – Age <3 years – Decreased peripheral perfusion • Fragile veins: – Elderly – Malnourished • Medications: – Warfarin – Antithrombotics – Corticosteroids • Uncooperative patient • Limited sites: – Previous phlebitis from multiple previous venous catheters or IV drug abuse – Planned extremity surgery – Previous mastectomy or axillary lymph node dissection – Shunts/arteriovenous fistulae

PHYSIOLOGY/PATHOPHYSIOLOGY

• IV access requires a relatively straight vein section and distention with adequate pressure of blood so that the vein is visible and/or palpable. • Preferred sites for IV access: – Upper extremity Metacarpal, dorsal venous network Forearm: Cephalic, basilica, median antebrachial Antecubital fossa: Cephalic, basilic, median cubital – Foot (mostly in children): Greater saphenous, lesser saphenous, dorsal venous network – Scalp (mostly age <6 months) – Umbilical (neonate) – External jugular • Avoid the following sites for IV access: – Proximal sites: Usually start with more distal sites and work proximally, if necessary – Sites over a joint: Flexion and extension will increase phlebitis and infiltration. – Distal cephalic vein in forearm is adjacent to the radial nerve (Infusion Nurses Society Guideline). – Veins on palmar side of wrist: Adjacent to median nerve (Infusion Nurses Society Guideline) – Visible valves • Preserve and avoid the following veins in the non-dominant arm for future dialysis in patients with chronic kidney disease (National Kidney Foundation Guideline): – Cephalic vein at wrist – Cephalic vein antecubital space

– Brachial basilic vein

PREVENTATIVE MEASURES

• If difficult IV access is anticipated, consider using the following techniques to enhance success: – Search extensively to find the best target vein before attempting an IV – Increase vein size Use a tourniquet or blood pressure cuff 8 cm above the site, with pressure less than the arterial diastolic pressure Place the extremity in the dependent position Use light tapping of the vein – If insufficient consider: Warming extremity (1)[A] Vasodilator: Nitroglycerin ointment topical (2)[B] • Sedation for uncooperative patients – Oral: Midazolam, clonidine, ketamine – Intranasal: Midazolam, dexmedetomidine – Intramuscular: Ketamine – Inhaled: Nitrous oxide, sevoflurane • Use local anesthetic to prevent pain and subsequent patient movement – Intradermal lidocaine – Transdermal lidocaine/prilocaine (EMLA) – Iontophoresis lidocaine (Numby Stuff) • Stabilize the vein with skin traction • Insert the needle with bevel up (3)[B] • Verify correct IV placement of the catheter – Aspirate blood from catheter – Fluid should infuse with minimal pressure. – Tourniquet applied proximally slows infusion rate. – No pain and no swelling with infusion – Infrared imaging and ultrasound may be able to detect infiltration.

PREOPERATIVE ASSESSMENT After 2 failed attempts refer to staff with advanced IV skills

TREATMENT Utilize vein visualization technology if needed • Transillumination involves utilizing a very bright light through the hand or placed adjacent to the vein site (4)[B]. – Works well for superficial veins – Least expensive method – Requires darkened room

– Device contacts skin. – One hand of the technician must hold the light. – Less effective with darker skin tones – Burns have resulted with non-approved devices. • Near infrared imaging. – Works well for superficial veins – More expensive – Does not require darkened room – Device does not contact skin. – Hands-free option for the technician – Not affected by skin tone – 2-dimensional image limits perception of vein depth. • Ultrasound (5)[A] – Works well for deeper veins – Most expensive; however, many anesthesia or emergency departments already own one. – Does not require darkened room – Device does contact skin and requires gel applied to skin. – One hand must hold ultrasound transducer. – Brachial veins adjacent to brachial artery and median nerve can be cannulated by experienced practitioners. – Deep veins may require longer catheters and/or guidewire techniques. • Emergent or alternative IV access can be attained as follows: – Central line placement in the internal jugular, subclavian, or femoral veins – Intraosseous – Tracheal; appropriate for some medications but not fluids. “NAVEL” mnemonic drugs include naloxone, atropine, vasopressin, epinephrine, and lidocaine. – Venous cutdown requires a longer insertion time.

FOLLOW-UP If IV access cannot be established, consider: • Alternate type of vascular access such as central line or intraosseous • Alternative routes for medication administration (oral, subcutaneous, and intramuscular)

CLOSED CLAIMS DATA

• Most common complications related to IV catheters (140 total claims): – Skin slough or necrosis: 28% – Swelling/inflammation/infection: 17% – Nerve damage: 17% – Fasciotomy scars from compartment syndrome: 16% – Air embolism: 8% (most claims for air embolism resulted from air in blood bags from cell savers) – Burns due to heat compresses used to treat IV infiltrations: 3% • 55% of IV complications were related to the extravasation of drugs or fluids, most

commonly: – Thiopental – Vasopressors (dopamine, dobutamine, epinephrine) – Calcium chloride • Interestingly, there were no claims for complications of IV catheters in patients who had previously had an axillary node dissection on the ipsilateral arm. • Overall median payment was $47,475.

REFERENCES

1. Lenhardt R, Seybold T, Kimberger O, et al. Local warming and insertion of peripheral venous cannulas. Br Med J. 2002;325:409–412.

2. Andrew M, Barker D, Laing R. The use of glyceryl trinitrate ointment with EMLA cream for IV cannulation in children undergoing routine surgery. Anaesth Intens Care. 2002;30(3):321–325. 3. Black JL, Pusic MV, Harmidy D, et al. Pediatric intravenous insertion in the emergency department bevel up or bevel down? Pediatr Emerg Care. 2005;21(11):707–711. 4. Katsogridakis YL, Seshadri R, Sullivan C, et al. Veinlite transillumination in the pediatric emergency department. Pediatr Emerg Care. 2008;24(2):83–88. 5. Constantino TG, Parikh AK, Satz WA, et al. Ultrasonography-guided peripheral intravenous access versus traditional approaches in patients with difficult intravenous access. Ann Emerg Med. 2005;46:456–461.

ADDITIONAL READING

• American Society of Anesthesiologists Closed Claims Project: Bhananker SM, Liau DW, Kooner PK, et al. Liability related to peripheral venous and arterial catheterization: A closed claims analysis. Anesth Analg. 2009;109(1):124–129. • Infusion Nurses Society. 2011. Infusion Nursing Standards of Practice. • National Kidney Foundation. 2006. Updates: Clinical Practice Guidelines Recommendations: Vascular Access.

CLINICAL PEARLS

• Be aware of the Infusion Nurses Society and National Kidney Foundation guidelines that outline which IV access sites to avoid. • Warming the extremity is effective in dilating veins. • Transillumination and infrared imaging facilitate superficial vein access. • Ultrasound is very effective for visualizing deeper veins.

DIFFUSION

Vijay Tarnal, MBBS, FRCA

BASICS DESCRIPTION

• Diffusion is the process by which molecules of a solute transfer through a layer or surface of a solution. It is a passive process, and the net movement of solutes occurs down a concentration (or electrical) gradient. • Laws defining diffusion: – Fick’s law states that the rate of diffusion of a substance across a unit area is proportional to the concentration gradient. This applies to a single homogenous phase, and the rate of diffusion is equal to flow multiplied by concentration. In a non-homogenous medium, the rate of diffusion is proportional to the tension gradient (diffusion of gas into solution). – Graham’s law of diffusion states that the rate of diffusion of a gas is inversely proportional to the square root of its molecular weight. • The transport of water and other molecules across biological membranes is essential to many processes in the human body. PHYSIOLOGY PRINCIPLES

• Diffusion can be described as: – Simple: A passive process by which solutes move from a region of higher concentration to one of lower concentration (down a concentration gradient). Oxygen, nitrogen, carbon dioxide, urea, steroids, and fatty acids are transported across membranes by simple diffusion. – Ion channel mediated: Ions channels are comprised of polypeptide subunits that are embedded in the phospholipid bilayer of the cell membrane. These ion channels render the cell membrane selectively permeable to certain ions such as Na+, K+, Ca2+ and Cl− (the positive or negative charge would otherwise preclude movement across the bilipid membrane). Opening and closing of these ion channels allows rapid changes to ion concentration on either side of the cell membrane. – Active transport: This involves movement of molecules against a concentration gradient, and is mediated by integral membrane proteins or carriers. Carriers can be uniport (specific substance), anti-port (exchange one substance for another), or symport (transport more than one substance); they require the expenditure of chemical energy (ATP). An example is the Na+-K+-ATPase carrier, which maintains a transmembrane gradient of Na+ and K+ ions. Secondary active transport involves transport of a substance and an ion together. The carrier has 2 separate binding sites. An example of this is glucose and Na+ transport across the intestinal mucosa. – Facilitated: A misnomer, as this describes the passive transport of substances from higher to lower concentration, which is facilitated by integral transport proteins. No energy is utilized. Glucose is transported into cells by this mechanism.

Tonicity Effects on the Red Blood Cell

• Osmosis is a specific type of diffusion, and involves the net movement of water across different concentrations. Tonicity is the measure of an osmotic pressure gradient produced between 2 compartments when separated by a semi-permeable membrane. – Isotonicity describes a solution where the concentration of solute is the same both inside and outside of the cell, with equivalent water movement into and out of the cell.

– Hypertonicity describes a higher concentration of solute outside the cell, with net water movement out of the cell.

– Hypotonicity describes a lower concentration of solute outside the cell, with net water movement into the cell.

• Diffusion across the alveolar–capillary membrane: Gas diffuses between the alveoli and capillaries based on partial pressure gradients, blood solubility, tissue surface area, and tissue thickness. In the blood, gas may dissolve and reach an equilibrium state based upon its solubility coefficient. The rate of gas transfer is directly proportional to tissue surface area. – Oxygen and carbon dioxide transfer occurs via simple diffusion between alveoli and capillary blood, as well as systemic capillary blood and tissue cells. – Red blood cells take 0.75 seconds to pass through the pulmonary circulation. Carbon dioxide reaches equilibrium in <0.1 seconds, whereas oxygen takes slightly longer due to its slower diffusion and binding to hemoglobin. • Neuromuscular transmission results from chemical messengers (acetylcholine), voltage-gated receptors, or mechanical stretch receptors of membranes. – Acetylcholine (ACh) release from the presynaptic membrane diffuses across the neuromuscular junction and binds to ACh receptors located on the postsynaptic membrane. This binding elicits ion channel mediated Na+ and K+ conductance down their gradient. The sudden influx of Na+ produces a positive end plate potential; if an action potential is reached/generated, it triggers excitation/contraction coupling in the muscle and brings about muscle contraction.

ANATOMY

• Phospholipid membranes of cells • Lung units: Alveolar–pulmonary capillary membrane • Nervous system: Blood–brain barrier, axons of neurons • Placenta

DISEASE/PATHOPHYSIOLOGY

• Tissue edema and interstitial lung disease (e.g., interstitial fibrosis) decrease the diffusion capacity and increase the distance between the alveolar membrane and diffusing gases. This results in increased Alveolar-arterial oxygen gradients (and ratios). • Acute tubular necrosis describes damage to the renal tubules from exposure to toxins or ischemia. It can impair diffusion of water or urea across the tubular membrane. PERIOPERATIVE RELEVANCE

• Nitrous oxide (N2O) and expansion of confined air spaces. N2O diffuses out of the blood and

into pockets of trapped gas within the patient. However, because nitrogen is poorly soluble in blood (1/34th the solubility compared to nitrous oxide), it takes longer for it to diffuse out of the air space and into the blood. This “lag time” results in larger amounts of nitrous entering the air space and an increase in volume and/or pressure within the confined space. In patients with intestinal obstruction, pneumothorax, pneumocephalus, or undergoing middle ear or eye surgery, this may cause serious damage. Endotracheal tube cuffs can also expand and have the potential to compromise tracheal mucosal perfusion, leading to edema and ischemia. Avoid using N2O in decompression sickness.

• Second gas effect: When N2O is administered in high concentration with a volatile inhalational agent of low solubility, the rapid N2O diffusion out of the alveoli into the

pulmonary capillaries produces an increasing concentration of the second agent (volatile agent) within the alveoli. As a result, there will then be an increased uptake of the second agent into the pulmonary capillaries, due to the higher partial pressure gradient between the 2 compartments. • Diffusion hypoxia: When N2O administration is discontinued, the rapid diffusion of N2O out of the pulmonary capillaries and into the alveoli will reduce the alveolar oxygen concentration. There will be a decreased O2 partial pressure driving gradient from the

alveoli to the pulmonary capillaries (and hemoglobin molecules), with the potential for tissue hypoxia. Increasing the fractional inspired concentration of oxygen can prevent and correct transient hypoxemia. • Local anesthetics should be injected in close proximity to the nerves that are to be blocked in order to improve diffusion into nerves (enhanced onset, strength, and duration of block). Vasoconstrictor additives decrease systemic uptake, leaving more drug at the site of action. • Blood brain barrier (BBB): Serves as both a physical barrier and a system for cellular transport mechanisms. Solutes move across the BBB by all of the 4 basic mechanisms of diffusion (simple, facilitated, ion channel mediated, and active transport). As a result, the BBB provides tight control over ion concentrations in the brain, as well as protects against toxins and changes in blood glucose. Drugs such as mannitol and hypertonic saline are used in the treatment of increased intracranial pressure (ICP); its therapeutic application is based upon establishing a hypertonic environment in the systemic vasculature, across the semipermeable BBB. Because water then moves freely by osmosis (down the osmolar concentration gradient), there is a net movement out of the intracellular and interstitial spaces of the BBB and into the systemic vasculature. This results in a decrease in intracranial volume, and hence pressure. • Absorption of drugs by enteric, sublingual, rectal, nasal, intramuscular, subcutaneous, transmucosal, and transdermal routes is dependent on the following factors: – Permeability coefficient which is related to the solubility of the drug in the tissue between the site of administration and the blood draining the tissue – Concentration gradient which is maintained by a high concentration of drug at the site of administration and rapid blood flow – Increased temperature enhances the rate of diffusion secondary to increased molecular movement.

• The placenta is, in effect, a lipid bilayer. – Some nutrients cross the placental barrier via active transport process. – Drugs cross via passive diffusion. However, protein binding and ionization on either side of the membrane affects the transfer of drugs. – Ion trapping: Fetal blood has a lower pH than that of the maternal blood. Weak bases, such as opioid analgesics and local anesthetics, become more ionized once they enter the fetal circulation. Because ions cannot cross the placenta, they are trapped on the fetal side of circulation. Ionized drug accumulation can occur in fetal distress where the pH becomes even lower. – General anesthesia for Cesarean sections is induced after prepping and with the surgeons scrubbed and ready for incision in order to decrease the effect of induction medications and volatile agents that can diffuse across the placenta.

REFERENCES

1. Sleath GW, Jenkins LC, Graves HB. Diffusion in anaesthesia. Can Anaesth Soc J. 1963;10:72–82. 2. Fanning GL, Colgan FJ. Diffusion hypoxia following nitrous oxide anesthesia. Anesth Analg. 1971;50:86–91. 3. Munson ES. Transfer of nitrous oxide into body air cavities. Br J Anaesth. 1974;46(3):202– 209.

ADDITIONAL READING

• Davis PD, Parbrook GD, Kenny GNC. Basics of physics and measurement in anaesthesia, 4th ed. Butterworth Heinemann Co.

See Also (Topic, Algorithm, Electronic Media Element) • Pneumothorax • Intracranial hypertension

CLINICAL PEARLS

• Exercise caution when using nitrous oxide for middle ear surgery, bowel surgery, or craniotomy. • Barring neuromuscular agents (high molecular weight and quaternary ammonium compounds), most drugs used in anesthesia practice can cross the placental barrier. • Inclusion of epinephrine with local anesthetics can prolong the block and reduce the risk of systemic toxicity by decreasing diffusion of drug from the injection site.

DOUBLE LUMEN TUBE (DLT) Siamak Rahman, MD

BASICS DESCRIPTION

• Double lumen endotracheal tubes (DLT) are the most commonly used technique for one lung ventilation (OLV) or lung isolation. Other techniques utilize a single lumen endotracheal tube with: – An enclosed bronchial blocker (Univent) – A wire-guided endobronchial blocker (Arndt blocker) – A Fogarty catheter as a bronchial blocker • Double lumen tubes are advanced into the airway and the distal lumen is positioned in either the right or left main bronchus; the proximal lumen is positioned in the trachea. By inflating the tracheal and bronchial cuffs, each lung will be ventilated through a different lumen of the tube, and lung isolation can be obtained by only ventilating the desired lumen at the proximal connector of the double lumen tube. • Indications for OLV include: – Isolating one lung from the other, in the case of bleeding, abscess, or bronchopleural fistula – Collapsing the right or left lung independently to aid with surgical visualization PHYSIOLOGY PRINCIPLES

• Double lumen tubes are designed to isolate ventilation; they have the added benefit over other techniques of facilitating deflation and suctioning, and administering continuous positive airway pressure (CPAP) to the deflated lung. The DLT consists of: – A tracheal and bronchial lumen – Cuffs on both lumens – Right or left sidedness

FIGURE 1. Double lumen tube showing a connector, stylet, 2 pilot balloons, lumens (tracheal and bronchial), and different color cuffs.

• Tracheal lumen: Shorter in length than the bronchial lumen. Designed to allow ventilation through its lumen above the carina. The tracheal lumen internal diameter sizes are 4.5 mm and 4.7 mm for 35F and 37F double lumen tubes, respectively; they are 2 mm larger than their bronchial lumens. The internal diameter of tracheal and bronchial lumens are equal in 39F and 41F double lumen tubes, at 4.9 mm and 5.4 mm, respectively. • Bronchial lumen: Longer in length than the tracheal lumen; distal tip is at a fixed distance from the trachea. Designed to allow ventilation through its lumen into the mainstem bronchus. • Cuffs: Respective pilot balloons are used to inflate and deflate the distal cuffs of the tracheal and bronchial lumens. The bronchial cuff is typically blue in color to aid with identifying its location (when bronchoscopy is performed through the tracheal lumen).

ANATOMY

• The tracheobronchial tree begins with the trachea at the level of the cricoid cartilage; it is approximately 11–13 cm long in the normal adult. It divides into right and left mainstem bronchi at the level of the carina (T5). • Left main bronchus: Takes a 45° angle off the trachea and bifurcates after 5 cm into the upper and lower lobes. • Right main bronchus: Takes a 25° angle off the trachea and bifurcates at a shorter distance in the normal adult (∼1–2.5 cm) into the upper, middle, and lower lobes.

DISEASE/PATHOPHYSIOLOGY • Vocal cord injury • Edema • Trauma

PERIOPERATIVE RELEVANCE

• Preparation: The placement of a DLT can be challenging due to its larger diameter and the need to be positioned into a specific mainstem bronchus. – In addition to a detailed airway examination, the anaesthetist should review films and images of the neck and thorax for changes in airway lumen, abnormal anatomy, masses, effusions and abscesses, hemorrhage and hematomas, if available. – Review pulmonary function. Patients with severe restrictive lung disease and very poor DLCO generally do not tolerate OLV. – Discuss surgical plan with the surgeon. Some patients will need to be kept intubated postoperatively with a single lumen tube (requiring a tube exchange) while others will need continued selective ventilation (leaving DLT in place and utilizing two different ventilators). – Equipment: Different sized laryngoscope blades and a fiberoptic scope. Consider having an indirect video laryngoscope, tube exchanger, or gum bougie available. – Difficult airway: In the event of a suspected (or unsuspected) difficult airway, it is better to place a single lumen tube and isolate the lung with a bronchial blocker. However, when a DLT is necessary, a single lumen tube can be placed and a tube exchanger can then be used to switch to a DLT. A fiberoptic scope should be used to confirm proper positioning. – Size: The Robert-Shaw is the most commonly used DLT. They are available in sizes 35, 37, 39, and 41F and refer to the outer diameter. Some proponents recommend choosing the largest tube that will fit in order to decrease the chance of migration and obstruction, which can result in hypoxemia, lung isolation failure, increased airway resistance, difficulty of passing a fiberoptic scope, or tracheal obstruction. Others propose inserting a smaller than conventional size to decrease trauma with insertion. One study demonstrated that choosing a smaller size did not influence the incidence of hypoxemia, need for repositioning, or success of lung isolation (1)[A]. Some studies suggest that measurement of the tracheal size from available CT or MRI imaging films can be used as a guide to choose DLT size (2)[A]. In general, most male adults take a size 37F or 39F and most female adults take a size 35F or 37F. – Sidedness: Left-sided DLTs are used for most cases that require lung isolation and OLV. If a left pneumonectomy is planned, the left DLT can be withdrawn back to the trachea before the surgeon staples the bronchus. Right-sided double lumen tube placement is more challenging because of the early branching of the right upper lobe and the proper positioning of the opening for ventilation (Murphy eye) of the endobronchial lumen at its origin (3)[B]. They were created primarily for left lung surgeries.

FIGURE 2. Correct placement. In both instances, the proximal tracheal lumen is located within the trachea. The left-sided DLT has the (distal) bronchial lumen located in the left mainstem bronchus. Notice the longer distance before the left

upper lobe take-off; thus providing an increased margin for error. The right-sided DLT has the (distal) bronchial lumen located in the right mainstem bronchus. The shorter distance before the right upper lobe take-off decreases the margin for error.

• Insertion: The tip of the tube is inserted just through the vocal cords and then immediately rotated 90° in the direction of the bronchus that one is aiming to intubate (4)[B]. • Confirming position: – Auscultation of the lungs and manual ventilation while the tracheal and bronchial lumens are selectively clamped and unclamped is one technique of determining proper positioning of the double lumen tube (5)[B]. – A fiberoptic scope is considered the gold standard, however, to confirm proper position of the double lumen tube (1)[B]. The fiberoptic scope is advanced through the tracheal lumen, and adequate positioning of the DLT is determined when the carina is visualized and the inflated blue cuff is observed in the desired bronchus (barely seen at the carina). For a proper right side DLT placement, it is necessary to look through the bronchial lumen with the fiberoptic scope to position the lateral slit of the Murphy eye at the site where the right upper lobe branches out.

FIGURE 3. View from fiberoptic bronchoscope inserted through the tracheal lumen above the carina on a correctly placed left-sided DLT.

REFERENCES

1. Amar D, Desiderio DP, Heerdt PM, et al. Practice patterns in choice of double-lumen tube size for thoracic surgery. Anesth Analg. 2008;106(2):379–383. 2. Brodsky JB, Macario A, Mark JBD. Tracheal diameter predicts double-lumen tube size: A method for selecting left double-lumen tubes. Anesth Analg. 1996;82:861–864. 3. Campos JH, Massa C, Kernstine KH. The incidence of right upper-lobe collapse when comparing a right-sided double-lumen tube versus a modified left double-lumen tube for left-sided thoracic surgery. Anesth Analg. 2000;90:535–540. 4. Koshy T, Nair SG. Positioning of double-lumen endobronchial tubes: Correlation between clinical and bronchoscopic findings. Indian J Anaesth. 2003;47(2):116–119.

5. Alliaume B, Coddens J, Deloof T. Reliability of auscultation in positioning of double-lumen endobronchial tubes. Can J Anaesth. 1992;39(7):687–690.

ADDITIONAL READING

• Lohser J. Evidence-based management of one-lung ventilation. Anesthesiol Clin. 2008;26(2):241–272.

See Also (Topic, Algorithm, Electronic Media Element) • One lung ventilation • Pulmonary ventilation • Perfusion matching • Pulmonary function tests

CLINICAL PEARLS

• The choice of a smaller than conventional DLT has not been associated with adverse outcomes such as hypoxemia, need for higher balloon cuff inflation pressures, or increased incidence of repositioning. • DLT should be advanced slowly, especially if a larger than conventional size is selected, to prevent damage to and rupture of the bronchi. • Placing a double lumen tube on a patient with a known difficult airway can make the process more challenging since the tubes are bulky and harder to place. • A left DLT can be technically used for all cases of lung isolation (3)[A].

DUCHENNE’S MUSCULAR DYSTROPHY (DMD) Jorge A. Galvez, MD

BASICS DESCRIPTION

• Duchenne’s muscular dystrophy (DMD) is a progressive neuromuscular disease. – Initially presents in early childhood as weakness and motor delay – Progresses to significant disability – Follows an X-linked recessive inheritance with female carriers and males being affected • Advances in cardiopulmonary therapy have improved survival and increased the need to undergo procedures that may require sedation or general anesthesia. • Succinylcholine is an absolute contraindication. Binding to extrajunctional receptors can result in acute hyperkalemia with resultant cardiac arrhythmias. Because muscular dystrophy disorders may go undiagnosed in the 1st and 2nd decades of life, succinylcholine should be avoided for routine airway management due to the risk of fatal reactions. • Mimics malignant hyperthermia where exposure to inhaled volatile agents (halothane, isoflurane, sevoflurane, desflurane) in patients with DMD may result in hyperthermia, hyperkalemia, and sudden death from cardiac arrest. EPIDEMIOLOGY Prevalence

• Most common of all muscular dystrophies • Live male births: 1 in 3,500 • X-linked recessive inheritance

Prevalence

Increased survival due to cardiopulmonary therapy advances Mortality

• Mean survival approximately 25 years • Death usually from progressive cardiomyopathy and/or ventilatory insufficiency

ETIOLOGY/RISK FACTORS

• X-linked recessive inheritance of dystrophin gene • Phenotype expressed in males • Females not affected, only carriers

PHYSIOLOGY/PATHOPHYSIOLOGY

• Dystrophin is responsible for connecting the cytoskeleton of each muscle fiber to the underlying basal lamina or extracellular matrix through a protein complex composed of several subunits. It prevents unregulated and unrestricted calcium entry into the

mitochondria. • In DMD, the recessive mutation on the X-chromosome prevents normal formation of dystrophin. Calcium can abnormally pass through the cell membrane or sarcolemma of mitochondria, resulting in increased osmotic effects and mitochondrial lysis. – Characterized by a complete loss of dystrophin – Becker’s muscular dystrophy is a less severe dystrophy caused by partial functioning of the dystrophin protein. • Malignant hyperthermia and DMD are genetically distinct diseases.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Avoid potentially fatal drug reactions, volatile anesthetics (halothane, sevoflurane, isoflurane, desflurane), succinylcholine. Patients should be scheduled as first starts, and if the anesthesia machine is utilized, it should be appropriately flushed, and the carbon dioxide absorber changed. • Assessment of baseline pulmonary dysfunction is critical. Goals should include avoidance of upper airway obstruction, hypoventilation, and atelectasis. Postoperative mechanical ventilation may be necessary, as well as deep inspiratory maneuvers and pulmonary toilet. • Operations with major blood loss or fluid shifts may result in compromised cardiac and respiratory function during recovery. Consider invasive monitoring for guidance.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Almost all DMD patients are symptomatic by 6 years of age: Difficulty running, jumping, climbing steps, waddling gait • Loss of ability to ambulate by 14 years of age • Snoring • GI reflux • Scoliosis with thoracic insufficiency

History

• Presents in early childhood as weakness and motor delay • Delayed walking beyond 15 months of age • Progressive lower extremity weakness

Signs/Physical Exam

• Gower’s sign: Patients use their arms when they get up from the floor. • Pseudo-hypertrophy of calves • Accessory muscle use • Proximal muscle weakness • Macroglossia

TREATMENT HISTORY

• Spine fusion for scoliosis, thoracic insufficiency • Gastrostomy or Nissen fundoplication for dysphagia

• Tracheostomy with ventilator dependence for respiratory insufficiency

MEDICATIONS

• Glucocorticoids may preserve respiratory muscle strength. • GI medications: H2 receptor antagonists, proton pump inhibitors, motility agents, laxatives for management of constipation • Cardiac medications can include angiotensin-converting enzyme (ACE) inhibitors, antiarrhythmics, and diuretics. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Pulmonary function tests demonstrate a restrictive pattern: – Pulse oximetry: If <95%, consider measuring end-tidal CO2

– Spirometry: A restrictive pattern is seen with a decreased forced vital capacity (FVC) and a normal or increased FEV1/FVC (FVC may decrease to a greater extent than the FEV1).

Measurements of the FVC may have predictive value for the risk of postoperative pulmonary complication (PPC). PPC is increased when the FVC <50%; it is significantly increased when <30%. Additionally, some suggest measuring a supine and upright FVC; a decreased FVC while supine may be more predictive of PPC. – Flow volume loops: Curve shifts rightward on the x-axis secondary to a decreased total lung capacity; all volumes are reduced; peak expiratory flow (PEF), maximal expiratory flow (MEF), and maximal inspiratory flow (MIF) are all reduced; however, flow reduction is congruent over the inspiratory and expiratory loops and the MEF50 ∼ MIP50.

• Markedly elevated creatinine kinase (CK) levels

CONCOMITANT ORGAN DYSFUNCTION

• Neurologic: Normal • Cardiac: Dilated cardiomyopathy, conduction defects, pulmonary hypertension, congestive heart failure – Patients have a limited ability to increase cardiac output in response to stress. – Dilated cardiomyopathy is present in up to 1/3rd of patients by age 14 years; reaches 100% by age 18 years. • ENT: Macroglossia, weak upper respiratory dilator muscles • Respiratory: Restrictive lung disease due to progressive deterioration in respiratory muscle strength (diaphragm, intercostal, and accessory muscles) – Hypoventilation – Impaired cough, predisposes to atelectasis and respiratory failure • Gastrointestinal: Dysphagia, dysmotility, aspiration risk, malnutrition (poor wound healing, muscle weakness, electrolyte abnormalities); may impair respiratory function if abdominal distention is present and not controlled. CIRCUMSTANCES TO DELAY/ CONDITIONS

FVC <30%; consider delay for training in noninvasive respiratory support

TREATMENT PREOPERATIVE PREPARATION Premedications

Use with caution as patients are very sensitive to sedative effects. The resultant hypoventilation may lead to rapid cardiopulmonary deterioration. Special Concerns for Informed Consent

• Review resuscitation guidelines and advanced directives for individual patients, as goals of care may vary depending on disease severity/stage. • Decisions regarding resuscitation parameters, attitudes toward prolonged dependency on mechanical ventilation, and tracheostomy should be clearly articulated and accessible in the medical record. INTRAOPERATIVE CARE Choice of Anesthesia

• Consider alternatives to sedation and general anesthesia whenever possible. • When general anesthesia is necessary, total intravenous anesthesia should be utilized.

Monitors

• Standard ASA monitors • Arterial line may help assess blood gases. • Major operations with expected high blood loss or fluid shifts (e.g., spine fusion) may warrant invasive monitors to guide resuscitation and postoperative management. Induction/Airway Management

• Airway support options depend on baseline pulmonary status. Intubation and mechanical ventilation may be necessary or preferred if: – Poor respiratory muscle strength – Ventilator dependent – Tracheostomy in situ – High risk for aspiration – Macroglossia, snoring is severe; patients are prone to airway obstruction with sedation. • The limited mobility of the mandible and C-spine: Makes jaw-thrust a less effective maneuver at receiving airway obstruction; may hinder vocal cord visualization on laryngoscopy. • Total intravenous anesthesia for induction • Muscle relaxation for intubation may not be necessary, given the baseline muscle weakness. Succinylcholine is absolutely contraindicated. • Other potential airway devices include noninvasive positive pressure ventilation, laryngeal mask airway, mechanical ventilation with mouthpiece, tracheostomy, BiPAP (bilevel positive pressure ventilator) with face-mask or nasal interface. Maintenance

• For GA cases, total intravenous anesthesia for maintenance. Muscle relaxation may not be necessary. • For MAC cases, titrate sedation cautiously and relieve airway obstruction.

Extubation/Emergence

• Consider noninvasive respiratory support to facilitate extubation (BiPAP or CPAP) • For FVC <50% (especially FVC <30%), consider: – Extubation directly to non-invasive respiratory support – Delaying extubation until respiratory secretions are well controlled – Delaying extubation until the SpO2 is normal or baseline

FOLLOW-UP BED ACUITY

• ICU setting is often necessary in order to provide: – Careful assessment of respiratory parameters such as hypoxemia due to hypoventilation, atelectasis – Secretion management, chest percussions – Manual assisted cough and mechanical insufflation-exsufflation (MI-E) device postoperatively – Mechanical ventilation • Optimize pain control. If sedation or hypoventilation occurs, delay ETT extubation 24–48 hours or use noninvasive positive pressure ventilation. • Consider enteral feeding with nasogastric or nasoduodenal tube in patients who cannot achieve adequate oral nutrition 24–48 hours postoperative. • Consider total parenteral nutrition in patients who develop ileus.

MEDICATIONS/LAB STUDIES/CONSULTS

• Pulmonary and cardiology evaluation as needed • Nutrition assessment, consider strategies for dysphagia

COMPLICATIONS

• Pulmonary: Increased when the FVC <50%, especially high when the FVC <30%. They include aspiration, weakness, atelectasis and decreased functional residual capacity (hypoxemia), and failure to wean from mechanical ventilation. • Cardiovascular: Hypotension and arrhythmias • Gastrointestinal: Postoperative gastroparesis, intestinal dysmotility, constipation; may be exacerbated by opioid analgesics. • Rhabdomyolysis secondary to depolarizing muscle relaxants (succinylcholine) • Malignant hyperthermia: Increased risk

REFERENCES

1. Hayes J, Veyckemans F, Bissonnette B. Duchenne muscular dystrophy: An old anesthesia problem revisited. Pediatr Anesth. 2008;18:100–106.

2. Birnkrant DJ, Panitch HB, Benditt JO, et al. American College of Chest Physicians consensus statement on the respiratory and related management of patients with Duchenne muscular dystrophy undergoing anesthesia or sedation. Chest. 2007;132(6):1977–1986. 3. Gurnaney H, Brown A, Litman RS. Malignant hyperthermia and muscular dystrophies. Pediatr Anesthesiol 2009;109(4):1043–1048. 4. Hopkins PM. Anaesthesia and the sex-linked dystrophies: Between a rock and a hard place. Br J Anaesth. 2010;104(4):397–400.

ADDITIONAL READING

• Muscular Dystrophy Association. http://www.mdausa.org/ See Also (Topic, Algorithm, Electronic Media Element) • Flow volume loops • Spirometry • Postoperative pulmonary complications • Hyperkalemia

CODES ICD9 359.1 Hereditary progressive muscular dystrophy ICD10 G71.0 Muscular dystrophy

CLINICAL PEARLS

• High risk of cardiac and pulmonary complications with sedation or anesthesia. Alternatives such as local anesthesia or minimally invasive procedures should be considered. • Avoid succinylcholine and volatile anesthetic gases (halothane, sevoflurane, isoflurane, sevoflurane) due to potentially fatal hyperkalemia and rhabdomyolysis, respectively. • Postoperative mechanical ventilation may be needed. Noninvasive positive pressure ventilation can facilitate extubation in patients with low FVC (<30%).

DYSPHAGIA

John Henao, MD Andrew Herlich, DMD, MD, FAAP

BASICS DESCRIPTION

• Dysphagia describes abnormal deglutition from impaired coordination, obstruction, or weakness affecting swallowing biomechanics. – Odynophagia: Painful swallowing – Globus (hystericus): Sensation of a lump in the throat • Dysphagia is often associated with significant comorbidities, including difficult airways, and also poses a risk for aspiration. • Patients with certain comorbidities frequently suffer from undiagnosed dysphagia.

EPIDEMIOLOGY Incidence

Overall lifetime incidence: 7% Prevalence

• Patients with CVA: >30% (1) • Patients 65 years or older: 40% (1) • Patients with Parkinson’s: 52–82% (1) • Patients with Alzheimer’s: 84% (1) • Institutionalized elderly: >60% (1) Morbidity

• In general, aspiration pneumonia occurs in 4–8 of every 1,000 patients admitted to a hospital in the US (2). • Aspiration occurs in up to 40% of patients with dysphagia, but rates vary by etiology. Mortality

• Dependent upon underlying etiology of dysphagia • Aspiration carries a risk of 3.8–4.6%.

ETIOLOGY/RISK FACTORS

• Chronic gastroesophageal reflux • Developmental disability • Increased age • Infection (botulism, diphtheria, Lyme, HIV, Candida, herpes, CMV, syphilis) • Medications: Anticholinergics, HMG-CoA reductase inhibitors, metoclopramide, chemotherapy agents, sedatives, antipsychotics, neuroleptics, antacids, antihistamines, and

NSAIDS • Neurologic impairment (cervical spinal injuries anterior > posterior, CVA, dementia, TBI) • Neuromuscular degeneration (ALS, multiple sclerosis, myopathies) • Respiratory (intubation >48 hours, tracheostomy, ventilator dependency) • Substances (alcohol, cigarettes) • Surgery related (head and neck or esophageal, cervical spine, intracranial, thoracic, postradiation effects)

PATHOPHYSIOLOGY

• Deglutition consists of 3 phases based on functional and anatomic characteristics. – Oral phase (preparatory and propulsive portions) alters the food bolus size, shape, volume, and pH. It involves voluntary and involuntary mechanisms controlled by CN V, VII, and XII, and is dependent on the lips, muscles of mastication, saliva, and tongue. Dysfunction is most frequently a result of poor tongue control. – Pharyngeal phase consists of the elevation of the entire pharyngeal tube including the larynx. This reflex is controlled by CN IX and X and is dependent on the epiglottis, hyoid bone, larynx, pharyngeal walls, soft palate, tongue, and vocal folds. Dysfunction of the pharyngeal phase represents the most common cause of aspiration. – Esophageal phase involves relaxation of the cricopharyngeal muscle and facilitates passage into the esophagus, after which the bolus is transported via primary peristalsis. This reflex is controlled by the medulla and is dependent on peristalsis and relaxation of the lower esophageal sphincter.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients may be hypovolemic. Reduced oral intake can result in hypernatremia with associated hypertonic hyperosmolality and intracellular compartment shrinkage. Assess volume status and create a fluid management plan. • Anticipate a difficult airway, as dysphagia is often the result of distorted anatomy. • Use caution when passing equipment (NG, OG, esophageal stethoscope, TEE). • Increased risk of aspiration makes a rapid-sequence intubation appropriate in certain cases (including pharyngeal disorders such as Zenker’s diverticulum or GERD).

PREOPERATIVE ASSESSMENT SYMPTOMS

• Oral or pharyngeal dysphagia: Aspiration pneumonia, change in voice or speech, difficulty initiating swallow, excessive salivation, nasal regurgitation, swallow followed by coughing, choking, or sensation of food sticking in the back of throat, reflexive cough combined with a wet voice (gurgling sounds produced on phonation of a prolonged “e”; has an 84% positive predictive value) (2), and weight loss • Esophageal dysphagia: Aspiration pneumonia, heartburn, pain during swallowing, regurgitation of food particles, swallow followed by sensation of food sticking in the throat or the upper chest, and weight loss • Absence of symptoms may indicate silent aspiration (more common in older males).

History

• Time of onset or frequency of symptoms; rapidity of progression • Association with liquids versus solids • Changes in dietary habits • Presence of pain • Drooling or facial muscular weakness • Weight loss or failure to thrive • Presence of halitosis • Aspiration or recurrent pneumonias • Trauma involving the head, neck, or chest • Neurologic or neuromuscular disorder • Ingestion of acidic material or foreign body

Pediatric Considerations

Dysphagia more commonly presents in children with multiple impairments. Additional history may include discussion of growth and development of the swallowing aperture; development of normal oromotor reflexes; maturation of feeding behavior; and acquisition of adequate nutrition for somatic growth. Signs/Physical Exam

• General: Syndromal/non-syndromal and craniofacial anomalies • Nose: Choanal atresia, congenital mass • Oral cavity: Dentition, gag reflex, palate, tongue, tonsils • Hypopharynx: Mass effect, pooling of secretions • Larynx: Congenital anomaly, mass, vocal fold mobility, voice quality • Neck: Osteophytes, presence of mass, thyroid gland • Pediatrics: Observe feeding and sucking and assess esophageal patency (consider passing an NG tube) TREATMENT HISTORY

• Previous gastric tube placement to avoid aspiration from oral feedings • Botulism toxin injections for achalasia

MEDICATIONS

• Nitrates, CCBs, sildenafil, or botulism toxin injections for treatment of achalasia (3) • Topical steroids or leukotriene receptor inhibitors for treatment of eosinophilic esophagitis

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Modified barium swallow (MBS) or fiberoptic endoscopic evaluation of swallowing (FEES)/with sensory testing (FEEST): Evaluate mechanical disorder. This is the gold standard for identifying patients who have the potential to develop pneumonia and for diagnosing aspiration and swallowing problems. • Upper endoscopy (EGD): Evaluate mechanical disorder

• X-ray: Evaluate aspiration (patchy opacity, lower lobe infiltrate, air space disease) or motility disorder (air–fluid levels vs. absence of stomach bubble) (3) • Manometry: Evaluate motility disorder (3) • pH monitoring: Evaluate reflux • CT head and chest: Evaluate masses (3)

CONCOMITANT ORGAN DYSFUNCTION • See “Etiology/Risk Factors” • Obstructive sleep apnea

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Suspected pneumonia from aspiration • Hypovolemia and hypernatremia • Newly suspected dysphagia. Absent swallow response on command, inability to manage oral pharyngeal secretions

CLASSIFICATIONS

• Penetration: Material enters the laryngeal area to the level of the true vocal folds. • Aspiration: Material moves below the true vocal folds and enters the trachea.

TREATMENT PREOPERATIVE PREPARATION Premedications

Consider IV fluid boluses if patient is suspected to be hypovolemic. Special Concerns for Informed Consent

Decreased cognitive function; may need consent from family member or power of attorney INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on type of surgery and patient comorbidities: – If general anesthesia is chosen, an endotracheal tube should be considered in patients at risk for aspiration. – If sedation is chosen, goals of sedation should be established; oversedation can result in aspiration, particularly in the supine position. Monitors

Standard ASA monitors

Induction/Airway Management

Difficult intubation should be anticipated in the oral phase disorders such as hypertrophic tonsils, and those with congenital defects. Maintenance

• Gastric suctioning to decrease stomach volume and risk of aspiration. It may be difficult to direct equipment to the esophagus in patients with velopharyngeal insufficiency as well as esophageal strictures, masses, or Schatzki’s ring. • Replete fluid deficits while balancing the risk of fluid overload that could exacerbate comorbidities.

Extubation/Emergence

• Patient positioning with the head elevated to prevent upper airway obstruction or aspiration • Ensure full reversal of neuromuscular blockade • Elderly or patients with Parkinson’s disease or Alzheimer’s may experience postoperative delirium, further increasing risk of aspiration. • Frequent assessments of airway patency

POSTOPERATIVE CARE BED ACUITY

Dependent upon the surgery, ability to maintain proper nutrition and hydration, and risk for aspiration, as well as the presence of comorbid disease MEDICATIONS/LAB STUDIES/CONSULTS

Consult: ENT, GI, speech language pathology (SLP), dietician, PT, and OT [B]. 66.8% of patients with dysphagia secondary to neurogenic causes experience improved swallow function after SLP services (4).

COMPLICATIONS

• Airway obstruction • Aspiration pneumonia • Bronchospasm • Chronic chest infections • Death • Dehydration • Malnutrition • Pediatric complications: Apnea, bradycardia, choking episodes, chronic noisy breathing, reactive airway disease, bronchitis, atelectasis

REFERENCES

1. Rofes L, Arreola V, Almirall J, et al. Diagnosis and management of oropharyngeal dysphagia and its nutritional and respiratory complications in the elderly. Gastroenterol Res Pract. 2011:818979. 2. Smith-Hammond CA, Goldstein LB. Cough and aspiration of food and liquids due to oralpharyngeal dysphagia: ACCP evidence-based clinical practice guidelines. Chest. 2006;129:154–168. 3. Lawal A, Shaker R. Esophageal dysphagia. Phys Med Rehabil Clin N Am. 2008;19(4):729– 745.

4. Ashford J, McCabe D, Wheeler-Hegland K, et al. Evidence-based systematic review: Oropharyngeal dysphagia behavioral treatments. Part III: Impact of dysphagia treatments on populations with neurological disorders. J Rehabil Res Dev. 2009;46(2):195–204. See Also (Topic, Algorithm, Electronic Media Element) • Aspiration • Gastroesophageal reflux disease (GERD) • Duchenne’s muscular dystrophy • Postoperative delirium

CODES ICD9

• 787.20 Dysphagia, unspecified • 787.21 Dysphagia, oral phase • 787.22 Dysphagia, oropharyngeal phase ICD10 • R13.10 Dysphagia, unspecified • R13.11 Dysphagia, oral phase • R13.12 Dysphagia, oropharyngeal phase

CLINICAL PEARLS

• Abnormal swallowing can cause aspiration and increases the likelihood of pneumonia. • History and symptoms concerning for malignancy: Worsening dysphagia, weight loss, alcohol or tobacco use, and long-standing GERD • JCAHO mandates that all stroke patients be screened for dysphagia before initiating an oral diet. • Despite normal EGD findings, esophageal biopsies need to be considered in the patient with intermittent solid-food dysphagia to rule out eosinophilic esophagitis. • MBS and FEES are the best tests available to evaluate dysphagia. • In the geriatric population, diagnosis is frequently delayed because dysphagia may present with atypical symptoms, or the symptoms may be attributed to other coexisting disorders. Additionally, elderly patients are less likely to seek medical care as they often tolerate symptoms better.

ECLAMPSIA

Daniel Mulcrone, MD Andrew Herlich, DMD, MD, FAAP

BASICS DESCRIPTION

Eclampsia describes new-onset convulsions or coma during pregnancy. It is • An emergency and carries a high risk of morbidity and mortality. Definitive treatment is delivery of the fetus. • Often a complication of severe preeclampsia; however, it can also occur in patients without hypertension and proteinuria • Can occur in the ante-, intra-, or postpartum period

EPIDEMIOLOGY Prevalence

Can occur in ∼5 per 10,000 live births (1,2); may be higher (5–100 per 10,000 live births) in developing countries (3)

Prevalence

• Antepartum: ∼40–50% • Intrapartum: ∼20–40% • Postpartum: ∼10–40%

Morbidity

• Preterm delivery (∼50%) • HELLP syndrome (hemolysis, elevated liver enzymes, low platelets, ∼10–15%) • Placental abruption (∼7–10%) • Acute renal failure (∼5–10%) • Disseminated intravascular coagulation (∼5%) • Cardiopulmonary arrest (∼5%) • Pulmonary edema (∼3–5%) • Aspiration pneumonia (∼2%) • Liver hematoma (∼1%) • Stroke (ischemic or hemorrhagic, ∼0.02%)

Mortality

• Maternal mortality ∼10% (63,000 maternal deaths annually) • Neonatal mortality ∼10%

ETIOLOGY/RISK FACTORS • Etiology unclear

• Maternal risk factors: – Demographics: Age >40 years old, African American ethnicity – Pregnancy associated: Nulliparity, multiple gestations, molar pregnancy – Comorbidities: Hypertension, renal disease, diabetes mellitus, factor V Leiden deficiency – Smoking: (Note: Surprisingly has been associated with a decreased risk of preeclampsia) • Fetal risk factors: – Gestational age <28 weeks • Paternal risk factors: – History of fathering a preeclamptic pregnancy with another woman – Mother with preeclampsia during gestation

PHYSIOLOGY/PATHOPHYSIOLOGY

• The etiology of eclamptic seizures remains unclear. Theories include systemic hypertension resulting in: – Cerebral over-regulation (vasoconstriction/vasospasm) which leads to hypoperfusion of the brain and localized ischemia – Loss of cerebral autoregulation leading to hyperperfusion and endothelial damage with edematous sequelae – Oxidative stress

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Control seizures and monitor for neurologic deficits which could signify an intracranial hemorrhage • Ensure maternal oxygenation, prevent maternal aspiration, and control hypertension (target SBP <160 mm Hg; DBP <110 mm Hg) • Prepare for urgent/emergent delivery

PREOPERATIVE ASSESSMENT SYMPTOMS

• May be asymptomatic prior to seizure • Preeclampsia symptoms: Visual disturbances (photophobia/blurred vision), headache, right upper quadrant pain, epigastric pain, altered mental status

History

• Eclampsia risk factors • Neurologic or seizure disorder

Signs/Physical Exam

• Seizures: Generalized tonic–clonic seizures lasting ∼60 seconds • Coma

MEDICATIONS

• Antiepileptics, magnesium • Antihypertensives

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Labs: – Urinalysis for proteinuria – CBC, especially platelets and Hct – CMP, including Mg2+ – Coagulation studies, including PT/INR, PTT, and fibrinogen – Type and Cross • Imaging studies: – CT head: Useful in identifying cerebral edema, loss of cortical sulci, and/or cerebral hemorrhage

CONCOMITANT ORGAN DYSFUNCTION

• Central nervous system (CNS): Risk of cerebral edema, cerebral hemorrhage, and/or alterations in cerebral autoregulation • Cardiovascular: Decreased central venous pressure (CVP), increased peripheral vascular resistance (PVR), coronary vasospasm, left ventricular hypertrophy, and/or increased sensitivity to catecholamines • Pulmonary: Airway edema, pulmonary edema, and/or increased risk of gastric aspiration • Renal: Acute renal failure, decreased glomerular filtration rate, and/or decreased clearance of uric acid • Hematologic: Hemoconcentration, increased blood viscosity, thrombocytopenia, and/or coagulopathy • Hepatic: Risk of liver hematoma, hepatocellular damage, and/or periportal hepatic necrosis • Placental: Uteroplacental insufficiency may lead to fetal hypoxia and/or intrauterine growth restriction. There is an increased risk of placental abruption and/or premature labor. CIRCUMSTANCES TO DELAY/ CONDITIONS

Delivery may be delayed if the parturient is stable and reassuring fetal heart tones are present.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Magnesium sulfate (first line for seizures) – Dosing: 4–6 g IV bolus over 15 minutes, followed by 1–2 g/hr for seizure prophylaxis – Therapeutic level: ∼6–8 mEq/mL – Contraindications: Heart block, Addison’s disease, hepatitis, myasthenia gravis, markedly reduced renal function – Pregnancy class A – Possible interactions: Nifedipine (hypotension) and non-depolarizing neuromuscular blockade (prolonged duration)

– Toxicity manifests with hyporeflexia and/or respiratory depression. Calcium gluconate (1 g IV) counteracts effects of magnesium. • Phenytoin (second line for seizures) – Dosing: 10 mg/kg dose over 1 hour – Contraindications: 2nd or 3rd degree AV block, bradycardia, Adams–Stokes syndrome – Pregnancy class D – Adverse reactions: Blood dyscrasia, bullous or purpuric skin rash, QRS widening, cardiac arrest (rapid infusion), hyperglycemia, and hepatic dysfunction • Diazepam (second line for seizures) – Dosing: 5–10 mg IV over 15 minutes; may be repeated every 15 minutes for a maximum dose of 30 mg – Contraindications: Narrow-angle glaucoma, hepatic failure, renal failure – Pregnancy class D: Freely crosses the placenta and accumulates in the fetal circulation – Adverse reactions: Cardiac arrest (rapid infusion), neonatal hypotonia, floppy infant syndrome, infantile kernicterus • Lorazepam (second line for seizures) – Dosing: 4 mg IV infused over 5 minutes; repeat in 10 minutes for a maximum dose of 8 mg IV in a 12-hour period – Contraindications: Narrow-angle glaucoma, hepatic failure, renal failure – Pregnancy class D: Freely crosses the placenta and accumulates in fetal circulation – Adverse reactions: Cardiac arrest (rapid infusion), neonatal hypotonia, floppy infant syndrome, infantile kernicterus • Hydralazine (first line for BP control) – Dosing: 5–10 mg IV every 15 minutes – Pregnancy class C – Possible interactions: Severe hypotension may occur if co-administered with MAOIs and/or beta-blockers. – Adverse reactions: Uterine hypoperfusion, reflex tachycardia • Labetalol (first line for BP control) – Dosing: 20 mg IV every 10 minutes up to a maximum dose of 300 mg – Contraindications: Cardiogenic shock, bradycardia, pulmonary edema, AV nodal block, reactive airway disease, and CHF – Pregnancy class C – Adverse reactions: Neonatal bradycardia • Nifedipine (second line for BP control) – Dosing: 10 mg PO TID titrated to effect for a maximum dose of 120 mg/day – Pregnancy class C – Possible interactions: May cause severe hypotension if administered with magnesium sulfate

Special Concerns for Informed Consent

Surrogate consent may be necessary if the patient is in a postictal state or is comatose. INTRAOPERATIVE CARE Choice of Anesthesia

• Neuraxial anesthesia (spinal or epidural)—if platelets and coagulation are normal. If an epidural catheter is already in place and properly functioning, the anesthetist may consider bolusing with a fast onset local anesthetic (chloroprocaine, lidocaine with bicarbonate, etc.) to avoid general anesthesia. – Hypotension may accompany initiation or bolusing of neuraxial anesthesia. Patients with preeclampsia are often intravascularly volume depleted (increased systemic vascular resistance). • General anesthesia may be necessary in emergent deliveries or if the patient has coagulation abnormalities. – Severe hypertension, with resultant intracranial hemorrhage, may accompany laryngoscopy. – Airway edema may increase difficulty of laryngoscopy. – Prolonged duration of non-depolarizing neuromuscular blockade in parturients on magnesium sulfate

Monitors

• Pulse oximetry: Decrease in SpO2 in the setting of pulmonary edema, respiratory depression,

and/or pulmonary aspiration • Blood pressure monitoring: Consider invasive blood pressure monitoring in the setting of refractory hypertension (BP >180/120) • CVP: May be useful in determining volume status and for infusion of vasodilators • EKG • Fetal heart tracing

Induction/Airway Management

• General anesthesia for emergent deliveries – Rapid-sequence intubation with cricoid pressure to minimize risk of aspiration – Avoid hypertensive response to laryngoscopy with deepening of intravenous or inhalational anesthetic, opioids (e.g., remifentanil), beta blockers (esmolol has a short duration of action), or vasodilators (e.g., nitroglycern, calcium channel blockers).

Maintenance

• General anesthesia is maintained with a combination of volatile anesthetic and nitrous oxide. – Following delivery of fetus, decrease volatile anesthetic to <0.5 MAC to minimize decreases in uterine tone. – IV opioids can be given following clamping of the cord.

Extubation/Emergence

Standard extubation criteria; may be precluded by airway edema. Additionally, ensure that the mother is awake, alert, and capable of protecting their airway.

FOLLOW-UP BED ACUITY

Consider ICU admission in patients with evidence of end-organ damage and/or need for mechanical ventilation MEDICATIONS/LAB STUDIES/CONSULTS

• Continue antihypertensive therapy until the blood pressure normalizes • Continue seizure prophylaxis for 24 hours following the last seizure • Labs: Follow Cr/BUN, platelets, INR/PT until values normalize • Consider consulting neurology, pediatrics, and/or maternal fetal medicine

COMPLICATIONS

• Recurrent seizures • Cerebral dysfunction • Pulmonary edema • Acute renal failure • Hepatic dysfunction • Disseminated intravascular coagulation • Placental abruption • Maternal death • Fetal death

REFERENCES

1. Katz VL, Farmer R, Kuller JA. Preeclampsia into eclamspia: Toward a new paradigm. Am J Obstet Gynecol. 2000;182:1389–1396. 2. Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol. 2005;105(2):402–410. 3. Morriss MC, Twickler DM, Hatab MR, et al. Cerebral blood flow and cranial magnetic resonance imaging in eclampsia and severe pre-eclampsia. Obstet Gynecol. 1997;89:561– 568. 4. Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med. 1995;333(4):201–205. 5. McDonald SD, Malinowski A, Zhou Q, et al. Cardiovascular sequelae of preeclampsia/ eclampsia: A systematic review and meta-analysis. Am Heart J. 2008;156:918–930. 6. Vigil-De Gracia P, Silvia S, Montufar C, et al. Anesthesia in pregnant women with HELLP syndrome. Int J Gynaecol Obstet. 2001;74:23–27. See Also (Topic, Algorithm, Electronic Media Element) • Preeclampsia • Magnesium

CODES ICD9 • 642.60 Eclampsia, unspecified as to episode of care or not applicable

• 642.61 Eclampsia, delivered, with or without mention of antepartum condition • 642.62 Eclampsia, delivered, with mention of postpartum complication ICD10

• O15.00 Eclampsia in pregnancy, unspecified trimester • O15.02 Eclampsia in pregnancy, second trimester • O15.9 Eclampsia, unspecified as to time period

CLINICAL PEARLS

• Molar pregnancy or antiphospholipid syndrome should be suspected if eclampsia presents in the first trimester of pregnancy. • Eclampsia may not necessarily be a continuum of preeclampsia and may exhibit no signs or symptoms of preeclampsia before onset of seizure activity. • Definitive treatment of eclampsia is delivery of the fetus. However, onset of eclampsia may still occur in the postpartum period. • Primary anesthetic objectives are cessation of the seizure, avoidance of maternal hypoxia, prevention of aspiration pneumonia/pneumonitis, management of hypertension, and prompt preparation for emergent delivery.

EJECTION FRACTION Amrik Singh, MD

BASICS DESCRIPTION

• The ejection fraction (EF) is defined as the percentage of end diastolic volume that is ejected during ventricular systole. EF usually applies to the left ventricle (LV). • Normal EF ranges from 55% to 70%.

PHYSIOLOGY PRINCIPLES

• Ejection fraction: EF = (EDV – ESV) / EDV – End diastolic volume (EDV): The volume of blood within the ventricle immediately prior to systole – End systolic volume (ESV): The volume of blood within the ventricle immediately after systole – Alternatively, the stroke volume is equal to the difference between the EDV and ESV (SV = EDV – ESV) EF = SV / EDV • As the LV pressure becomes higher than the aortic pressure during systolic contraction, the aortic valve opens. A portion/fraction of the EDV is ejected into the aorta until the aortic valve closes again and the LV begins its isovolemic relaxation phase. Even at a constant contractility, the measured EF can vary with varying preload and afterload. • Frank Starling Law: A larger LV end diastolic volume leads to increased cardiac muscle length with a higher force of contraction that consequently results in an increased EF. This mechanism is exhausted in failing hearts. • Echocardiography is the most frequently used technique to measure EF using M-mode, 2D and 3D modalities. – M-mode measures the fractional shortening (FS) of the mid-LV end diastolic internal diameter during systole. Doubling the FS value can be used to obtain a rough estimate of EF in the absence of optimal images or in the interest of time. Its accuracy is decreased in a ventricle with asymmetric contractility along different planes. The normal range for FS is 25–45%. – 2D echocardiography uses Simpson’s method to calculate EDV and ESV of the LV. The method is based on the division of the LV into multiple discs and summation of individual disc volumes. The data is acquired from apical (transthoracic) or mid-esophageal (TEE) 2and 4-chamber views and is less affected by abnormal size or asymmetry of the ventricle. Fractional area change (FAC), which is a rough estimation of EF, measures percent change in the area during systole and is calculated by tracing the end diastolic and systolic area of the mid-LV. It is not accurate in a ventricle with asymmetric contractility along its long axis. – 3D echocardiography eliminates some of the inherent geometrical assumptions and

mathematical modeling needed in the M-mode and 2D methods because the LV image is acquired in its true shape and provides more accurate assessment in the presence of regional dysfunction. • Left ventriculography: – A contrast agent is injected directly into the LV cavity and images are obtained during diastole and systole, most commonly in a 30° right anterior oblique view. – This method is commonly used during diagnostic or therapeutic cardiac catheterization/angiography. – Contraindicated in patients at risk for contrast-induced nephropathy • Magnetic resonance imaging: – Has a high accuracy due to excellent resolution with minimal inter-observer variability and is considered the gold standard – It also uses Simpson’s method to calculate LV volume. – Associated with minimal adverse effects • Computed tomography: – Requires IV contrast administration – A slow sinus rhythm is necessary to obtain good quality images. – Can also evaluate any calcification in the coronary arteries • Nuclear medicine technique: – Involves injection of radiotracer material intravenously and analyzing recorded cardiac images – For example, a patient’s red blood cells are labeled with Technetium-99 and re-injected intravenously followed by imaging of the LV at a high frame rate.

ANATOMY

• Depolarization leads to calcium influx into the myocardial cells. The amount of calcium influx coupled with preload (length of cardiac muscle) and afterload (systemic vascular resistance, blood viscosity, aortic valve stenosis) determine the force of contraction. • The heart works as a closed circuit; therefore left and right ventricles, although different in size, thickness, and chamber pressure, have identical EF. • Regional wall motion and aneurysmal abnormalities will impact EF calculations that use linear measurements.

DISEASE/PATHOPHYSIOLOGY

• EF is a good clinical indicator of LV systolic function. A low EF indicates systolic dysfunction due to myocardial ischemia or non-ischemic cardiomyopathy and often leads to signs and symptoms of congestive heart failure (CHF). CHF in the presence of normal EF indicates significant diastolic dysfunction. The lifetime risk of developing CHF is 20% for both men and women. • In the presence of normal ventricular contractility, a higher EDV (e.g., increased venous return or aortic insufficiency) will result in increased EF. Therefore, it is important to report the preload status at the time of the EF measurement. • Low afterload (e.g., low systemic vascular resistance or severe mitral regurgitation) will also result in a higher EF. A normal measured EF in these conditions may actually indicate contractile dysfunction.

PERIOPERATIVE RELEVANCE

• The primary goal in patients with low EF is to: – Focus on the etiology of systolic dysfunction – Optimize preoperative cardiovascular status – Maintain baseline hemodynamics – Minimize cardiovascular stress – In patients with ischemic heart disease, optimize preoperative medical management, decrease preoperative anxiety, and decrease myocardial oxygen demand by controlling heart rate, contractility, and wall tension. Improve myocardial oxygen supply by maintaining optimal hemoglobin levels, oxygenation, and coronary perfusion pressure (CPP). • Elective surgery should be delayed in the presence of active heart failure. • Avoid excessive myocardial suppression by anesthetic agents; expect slow circulation time for all drugs and slow emergence from anesthesia. • Invasive cardiovascular monitoring may be necessary to guide intravascular volume status and control hemodynamics closely. • Patients with significantly low EF (<35%) may have had cardiac resynchronization therapy and/or an implantable cardioverter-defibrillator device placed that will need to be managed appropriately. • Patients with chronic CHF have down-regulation of β-1 receptors that might make them less responsive to β-agonist therapy in improving contractility and EF. Chronic β-blocker therapy up-regulates β-1 receptors in these patients and has been shown to improve survival. • The prevalence of diastolic heart failure increases with age. LV hypertrophy from chronic hypertension or aortic stenosis also contributes to increased stiffness and decreased compliance. Maintain preload and adequate diastolic time. Lusitropic agents such as milrinone may be effective in improving cardiac output. Most anesthetic agents do not impair diastolic function. Pediatric Considerations

The myocardium in children, especially neonates, is less compliant compared to an adult heart. Therefore, it is much more sensitive to small changes in in heart rate, preload, and afterload EQUATIONS

• SV = EDV − ESV; where SV is stroke volume, EDV is end diastolic volume, and ESV is end systolic volume • EF = (100 × SV) / EDV; where EF is ejection fraction, SV is stroke volume, and EDV is end diastolic volume • FS (Fractional Shortening) = 100 × [(LV diastolic diameter) – (LV systolic diameter)] / (LV diastolic diameter) • FAC (Fractional Area Change) = 100 × [(LV diastolic area) – (LV systolic area)] / (LV diastolic area) • CPP (Coronary Perfusion Pressure) = (Diastolic blood pressure) – (Left ventricular end

diastolic pressure)

GRAPHS/FIGURES See Table

REFERENCES

1. Lloyd-Jones DM, Larson MG, Leip EP, et al. Lifetime risk for developing congestive heart failure: The Framingham Heart Study. Circulation. 2002;106:3068–3072.

2. Ramani GV, Uber PA, Mehra MR. Chronic heart failure: Contemporary diagnosis and management. Mayo Clin Proc. 2010;85:180–195. 3. San Román JA, Candell-Riera J, Arnold R, et al. Quantitative analysis of left ventricular function as a tool in clinical research: Theoretical basis and methodology. Rev Esp Cardiol. 2009;62:535–551. See Also (Topic, Algorithm, Electronic Media Element) • Cardiac output • Congestive heart failure

CLINICAL PEARLS

• EF is a measure of systolic function of the heart. • A low EF often indicates ischemic or non-ischemic cardiac disease. • A normal EF does not rule out heart failure, and is seen with diastolic dysfunction. • Assure preoperative optimization and maintain a positive myocardial oxygen supply and demand ratio perioperatively. • Be aware of low cardiovascular reserve and excessive myocardial depression by anesthetic agents.

ELECTRICAL SAFETY IN THE OPERATING ROOM David P. Frey, DO Adam Thaler, DO

BASICS DESCRIPTION

• An electrical shock or injury occurs when a person is part of, or completes, an electrical circuit. • Electrical hazards in the operating room (OR) are numerous, making proficiency in safety imperative. • Electrical injury is classified as: – Macroshock: Large amounts of current; results range from discomfort to death – Microshock: Minute, imperceptible amounts of current that are capable of death in electrically susceptible patients • A standard power cord consists of a: – Hot wire: Carries current from the source to equipment – Neutral wire: Carries current from equipment back to the source – Ground wire: A third wire, positioned at the lowest position, and functions as a safety device. Its prong is longest to ensure that it is the first to plug into an outlet. • Grounding is a confusing term since it has 2 separate meanings in reference to power and to equipment. EPIDEMIOLOGY Prevalence

40% of electrical accidents in hospitals occur in the OR (1).

Morbidity

Burns, seizures, muscle contraction, respiratory paralysis, and ventricular fibrillation (Vfib) Mortality

Not available

ETIOLOGY/RISK FACTORS

• Any piece of electrical equipment is a source of potential hazard that demands understanding of electrical safety from all members of the care team. Some examples include: – Ungrounded equipment; if the ground wire to a piece of equipment is damaged, it is possible for charge to build on the case of the equipment and eventually discharge to a patient, provider, or both. – Damaged power cords – Internal cardiac devices (ICDs)

– Esophageal temperature probes – Conductive fluids – Electrosurgical units (ESUs) – Lasers – EKG leads • Electrically susceptible patients: Refers to a person with some kind of conducting device in direct contact with the heart over a small area (pacing wire, central catheter, etc.).

PHYSIOLOGY/PATHOPHYSIOLOGY

• Electricity is commonly thought of as a flow of charge through a conducting material. It requires a source of voltage, 2 points at differing electric potentials, and a closed circuit that is able to conduct charge. • Ohm’s law: States that voltage is equal to the current multiplied by resistance: V = I × R (for DC current); similar to the cardiovascular system where pressure is equal to cardiac output times resistance. – Voltage (V): The force driving current against the resistance in a circuit; measured in volts. It is the potential difference of charge (high potential versus low potential). It is similar to pressure. – Current (I): The flow of charge measured in amperes. It is traditionally thought of as the flow of positive charge from a high potential (positive terminal) to low potential (negative terminal). However, current is measured as the flow of negatively charged electrons; thus, electron flow is opposite (from low to high potential) of the positive charge flow. Current is classified as Direct (DC; flows in one direction only) or Alternating (AC; changes directions periodically; what is supplied by utility companies). It is similar to cardiac output. – Resistance (R): Can be thought of as the opposition to the flow of current; unit is Ohms. Human tissue is inherently resistant to current. The higher the resistance, the more voltage that is necessary for current to pass. – Impedance (Z): For AC, resistance is referred to as impedance (V = I × Z). • Radio frequency: Measured in Hertz (Hz) and refers to the number of times in 1 second that an AC reverses direction. Power from the utility company is AC of 120 V at 60 Hz. Common radio frequencies (5): – 60 Hz: Household appliances – 200 kHz–3.3 MHz: Electrosurgical equipment – 54–880 MHz: Television signal • The severity of injury is dependent on the amount of current, the duration of flow, and current density (the amount of current applied per unit area). Current density is increased when there is an increase in the current or when it is applied to a smaller area. ESUs operate on this principle by concentrating current at the ESU tip. • Macroshock: Refers to large amounts of current flowing through a person. The effect of a 60 Hz current on an average person for 1 second (2): – 1 mA: Threshold of perception – 5 mA: Maximal harmless current – 10–20 mA: “Let go” current before sustained muscle contraction – 50 mA: Pain, fainting, mechanical energy; heartbeat and respiration continue

– 100–300 mA: Ventricular fibrillation; respiratory center intact • Microshock: Minute amounts of current that can result in injury or death only in electrically susceptible patients. – 0.1 mA: Ventricular fibrillation (Note: the threshold for perception with macroshock is 1 mA). – 0.01 mA: Recommended maximal leakage current for OR devices • DC is generally considered safer than AC; it takes approximately 3 times the DC current to produce the injuries seen with AC at 60 Hz. This, however, does not mean that DC is benign as death can still result. • Temperature: Current passing through any type of resistance will raise the temperature of that substance, potentially leading to thermal injury ranging from cell destruction to burns. • Electrosurgery: The high frequency used will not cause cardiac fibrillation, only burns. – Unipolar: Current will pass through the patient, through the attached return plate, and back to the ESU (completing a circuit). The return plate (large blue adhesive pad) is a dispersive electrode with a large surface area that provides a low current density pathway. If incorrectly applied, it is possible for a high current density to develop and burn the patient. If not applied or a wire is broken, it is possible that the current will find a different route through the operator, EKG leads, prosthetic devices, etc., and result in injury. – Bipolar: This device only passes current between the 2 tips of an electrode resembling a forceps. The active and return electrodes are the 2 blades, so there is no need for a return plate and much less power is needed compared to a unipolar electrode. • ICD interference: The current may be misperceived by the device as an arrhythmia and elicit anti-tachycardic pacing or shock delivery. Newer devices have improved insulation, and the development of frequency-based devices will be able to recognize interference. However, the ASA recommends reprogramming the device directly or turning off with a magnet before surgery.

PREVENTATIVE MEASURES

• Differences exist in the electrical safety measures built into operating rooms that the anaesthetist should be aware of. • Isolated power system: Most OR power sources are built with an isolation transformer that separates the outlet from the actual power source. It greatly diminishes the risk of shock by requiring that a person be in contact with both lines of an isolated power system to complete the circuit. In contrast, for a non-isolated power source, standing on the ground completes a circuit; thus, a person standing in contact with the ground will complete a circuit by touching the hot wire (3,4). • Line isolation monitor (LIM): Continuously monitors the integrity of the isolated system. The isolation is degraded with every device that is connected, secondary to inherent leakage currents. Integrity of the system is displayed in milliamperes (mA) and alarms if the total leakage current is 2–5 mA. This is not a value of current flowing; it is the current that would be able to flow during a fault. So the alarm does not necessarily signal an emergent situation but rather a degradation of isolation. Devices will continue to function but the safety of the isolated system is gone. It should be noted that the LIM is not designed to protect against microshock, as its threshold is set above 1 mA (3,4,5).

• Ground wire: The third and lowest prong of a power cord is meant to offer a path of lowest resistance in case of a fault. Most of the current will return along the ground wire away from the person. If this is not present or if it is broken, the person will experience a considerable, and perhaps lethal, shock. In addition, it dissipates leakage current that is potentially lethal to electrically susceptible patients. • Hospital-grade outlets: Identifiable by a green dot. Have been shown to have greater integrity in ground wire connection than non-hospital-grade outlets. • Emergency outlets: Identifiable by a red outlet. These outlets provide power from a backup generator in case of a power outage (2). • Hospital-grade plugs: Allow for visible inspection of ground wire integrity through the use of clear plastic or easy disassembly (2) • Emergency power: All hospitals are required to have backup power. Generators should start within a few seconds of detecting loss of power from the utility company. As such, generators may not turn on if power is lost only to isolated rooms within the hospital (2). • Damaged equipment and power cords should not be used until repaired. All equipments must undergo regular maintenance and inspection (2). • Grasp cords by their plugs when removing. • Keep cords off of the ground in order to avoid puddles of conductive liquids and damage from rolling equipment in addition to their potential to trip members of the care team. • Multi-outlet extension boxes are prone to fluid contamination. They should be avoided, if at all possible. • Electrosurgery: Ensure proper placement of the return plate. Encourage the use of a bipolar electrodes in electrically susceptible patients. Bipolar electrodes create little, to no, sparking and have not been recorded as a cause of fire.

PREOPERATIVE ASSESSMENT • LIM-equipped rooms will alarm at a preset limit of leakage current, usually 2–5 mA. • Microshock will result in Vfib on EKG in electrically susceptible patients. • The need for higher settings on the ESU may signal an improperly placed or faulty return pad.

TREATMENT • In the event of a LIM alarm: – Systematically unplug the last piece of equipment connected, as it is probably the faulty one. Faulty equipment should be removed and serviced. – If the equipment is life-sustaining and essential, it could continue to remain in use. However, the system is no longer isolated and there is a potential for serious shock. – It is possible that no equipment is faulty and there are simply too many devices since leakage current is additive. Excessive use of extension cords will also increase the leakage current. – If the offending device cannot be found, the search should expand to the actual outlets, extension boxes, and environmental hazards such as puddles.

• In the event of a power outage: – Most times, the emergency generator will provide power, but a contingency plan should already exist with necessary equipment. – Battery-supplied light sources: Laryngoscopes and cell phones can serve as light until flashlights are located. – Battery-powered monitors and workstation: Prepare for hand ventilation. Inhaled anesthetics, other than desflurane, will continue to be vaporized pneumatically.

FOLLOW-UP Patients should be informed if they are involved in a perioperative electrical outage or accident and be provided necessary care.

REFERENCES

1. runer J, Aronow S, Cavicchi R. Electrical incidents in a large hospital: A 42 month register. J Assoc Adv Med Instr. 1972;6:222–230. 2. Raftery EB, Green HL, Yacoub MH. Disturbances of heart rhythm produced by 50-Hz leakage currents in human subjects. Cardiovasc Res. 1975;9:263–265. 3. Hutchisson B, Baird MG, Wagner S. Electrosurgical safety. AORN J. 1998;68(5):829–830. 4. Bernstein MS. Isolated power and line isolation monitors. Biomed Instrum Technol. 1990;24:221. 5. Massarweh NN, Cosgriff N, Slakey DP. Electrosurgery: History, principles, and current and future uses. J Am Coll Surg. 2006;202(3):520–530.

ADDITIONAL READING

• Barash PG, Cullen BF, Stoelting RK, eds. Clinical anesthesia, 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2006.

See Also (Topic, Algorithm, Electronic Media Element) • Burns • Fire in the operating room • Ventricular fibrillation

CODES ICD9 994.8 Electrocution and nonfatal effects of electric current ICD10 T75.4XXA Electrocution, initial encounter

CLINICAL PEARLS

• Manufacturers can accomplish leakage current standards by keeping their power cords short. By using an extension cord you are increasing the leakage current. • LIMs do not protect against microshocks.

ELECTROCONVULSIVE THERAPY (ECT) Stephen M. McHugh, MD Li Meng, MD, MPH

BASICS DESCRIPTION General

• Electroconvulsive therapy (ECT) is the transcutaneous delivery of an electrical stimulus to a patient’s brain in order to produce a generalized seizure. It was first developed in the 1930s as a treatment for schizophrenia, and performed without anesthesia until the 1960s. • Current indications include major depression, bipolar disorder, and certain subtypes of schizophrenia. • The typical course of therapy includes 2–3 sessions per week for 3–4 weeks followed by weekly or monthly maintenance sessions. • Leads are usually placed in a bitemporal or right unilateral configuration. After the electroshock is delivered by the psychiatrist, monitoring of both the central and peripheral nervous systems is performed. • CNS effects are desired. EEG monitoring typically reveals a latent period (2–3 seconds) that is followed by a tonic (10–12 seconds) and then a clonic (30–50 seconds) phase. A seizure length of at least 25 seconds is considered necessary for therapeutic effect. The first session often includes an upward titration of the electrical stimulus to determine the dose required to achieve the desired seizure length. • The peripheral effects are “side effects” that are monitored and minimized to prevent harm to the patient. They include autonomic nervous system discharge as well as uncontrolled motor activity. – Autonomic nervous system: Electrical stimulation of the brain is associated with an increased parasympathetic discharge (corresponds with the tonic phase; 10–15 seconds) followed by an increased sympathetic discharge (corresponds with the beginning of the clonic phase, but lasts 5–7 minutes). • Contraindications include: – Absolute: Pheochromocytoma – Relative: MI in past 3 months, CVA in past 3 months, intracranial mass, elevated ICP (ECT can significantly increase cerebral blood flow), cardiac conduction abnormalities, aortic/cerebral aneurysms, high-risk pregnancy Position

• Supine • Left uterine displacement should be used for all parturients in the second and third trimesters. Incision

None

Approximate Time

Less than 20 minutes EBL Expected None

Hospital Stay

Less than 1 day

Special Equipment for Surgery

• Electrical leads to produce seizure • Electroencephalogram (EEG) • Electromyogram (EMG) • Second blood pressure cuff or tourniquet

EPIDEMIOLOGY Prevalence

• 14 million Americans are diagnosed with depression each year. • Approximately 400,000 ECT treatments are performed each year.

Prevalence

• Lifetime risk of major depression is 17%. • Depression resistant to pharmacotherapy is present in up to 50% of patients.

Morbidity

Dental injury is the most common complication. Mortality

4 in 10,000 procedures; cardiac events comprise 67% of deaths. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Rapid loss of consciousness and recovery for a short duration procedure; often an out-of-OR procedure. • Airway management is usually non-invasive with a bag-mask device (Ambu, Jackson-Reese). • Anticipate and prevent adverse peripheral effects including hemodynamic changes and the potential for biting or extremity injury • Avoidance of medications that increase seizure threshold or decrease duration; the majority of anesthetic drugs have effects on the threshold.

PREOPERATIVE ASSESSMENT SYMPTOMS

Depression, mania, psychosis, and catatonia

History

• Psychiatric illness including major depression, bipolar disorder, and schizophrenia • Focused cardiac and neurologic system history to look for relative contraindications as well as patients who are at increased risk for adverse events Signs/Physical Exam

• Careful airway exam to assess the ability to ventilate as well as intubate • A dental exam should document any baseline damage and be confirmed with the patient. • Focused cardiac and neurologic exam as indicated by the history

MEDICATIONS

• Antidepressants (MAOIs, TCAs, SSRIs, SNRIs, and atypical antidepressants); direct acting sympathomimetics may have an exaggerated effect in patients taking TCAs. • Lithium is usually held for 3 days prior to ECT as it can interfere with effects of neuromuscular blocking drugs, barbiturates, and benzodiazepines. • Antipsychotic medications • Antihypertensive medications should be continued to avoid extreme hypertensive events during the procedure. • Anticonvulsant medications should be held on the morning of the procedure.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• EKG to screen for relative contraindications including arrhythmias and evidence of myocardial ischemia • CXR if history or exam shows evidence of pulmonary disease that could affect ventilation during procedure • Non-contrast head CT if concern for possible intracranial mass • Blood glucose if patient requires insulin for DM • Potassium level if patient has renal failure, is taking a potassium-sparing diuretic, or has other risks for hyperkalemia CONCOMITANT ORGAN DYSFUNCTION

• Special attention should be paid to cardiac and neurologic comorbidities. • ECT has been reported to convert atrial fibrillation to sinus rhythm. Because of this, all patients undergoing ECT with AF should be fully anticoagulated for at least 3 weeks prior to ECT. • Pregnancy is not a contraindication to ECT and is considered safe in all trimesters (1)[C].

TREATMENT PREOPERATIVE PREPARATION Premedications

• Glycopyrrolate (0.2 mg IV) can decrease secretions and the risk of bradyarrhythmias.

• Benzodiazepines should be avoided as they increase the seizure threshold. • In patients at increased risk of aspiration pneumonitis, consider H2 blockers, non-particulate antacids, and promotility drugs. • Ketorolac, PO NSAIDs, or acetaminophen can be given prophylactically to patients experiencing headache or myalgias after previous ECT treatments. • Caffeine may occasionally be given intravenously to increase seizure duration.

Special Concerns for Informed Consent

• Communicate the potential for post-procedure amnesia, headaches, myalgias, and dental injuries. • Patients with severe psychiatric disorders may not be able to consent for themselves.

Antibiotics/Common Organisms Antibiotics are not indicated. INTRAOPERATIVE CARE Choice of Anesthesia

• Most commonly performed with general anesthesia using an IV induction agent, succinylcholine, and bag-mask ventilation. – The “gold standard” induction agent is still considered methohexital (0.75–1.0 mg/kg) due to its minimal effect on seizure threshold and short duration of action. However, shortages and lack of availability often make it necessary to utilize other medications. – Propofol (0.75 mg/kg) is associated with decreased hypertension and equal seizure quality as compared to methohexital (2)[A]. – Thiopental, etomidate, and ketamine have also been used successfully. – Remifentanil (1 mcg/kg) can reduce the dose of IV induction agent needed and increase the likelihood of adequate seizure duration (3)[A]. – Avoid barbiturates in patients with acute intermittent porphyria. • Mask induction with sevoflurane has been used successfully for patients with difficult IV access; however, this may be associated with prolonged induction and recovery times.

Monitors

• ASA standard monitors • A second BP cuff (or tourniquet) is usually placed on the non-IV arm or lower extremity and is inflated above the systolic BP prior to induction. This technique prevents neuromuscular blockade distally and allows observation of motor duration of the seizure. • BIS monitoring may be useful for predicting the seizure duration (4)[B]. • AICDs must be deactivated as seizure activity may be mistaken for a cardiac arrhythmia and a back-up defibrillator should be available. Pacemakers should be set to a fixed-rate (demand mode) pacing prior to ECT.

Induction/Airway Management

• Standard induction with an IV agent following pre-oxygenation. – Mask ventilation with an oral or nasal airway as needed; hyperventilation can be used to decrease the seizure threshold.

– A bite block or mouth guard should be used to avoid dental injury during the seizure. – Succinylcholine (1 mg/kg) is given after induction. In the event that a depolarizing agent is contraindicated, a non-depolarizing neuromuscular blocking drug should be used. This may result in prolonged procedure duration. Avoid excessive doses of succinylcholine to prevent ongoing paralysis after the patient regains consciousness. • Intubation may be necessary for patients at risk for airway obstruction/difficulty with bag mask ventilation. A rapid-sequence intubation with cricoid pressure is indicated for patients at increased risk of aspiration. • A full array of emergency airway equipment must always be available.

Maintenance

• Parasympathetic discharge occurs first and can present as bradyarrhythmias or asystole. Treatment with an anticholinergic medication may be appropriate. • Sympathetic discharge follows, typically with hypertension and tachycardia. Ventricular tachycardia is also possible. These conditions are usually transient and stop with completion of the seizure, but short-acting drugs such as esmolol, labetalol, nitroglycerin, or nicardipine may be necessary.

ALERT Hypotension should not be treated with mixed-acting sympathomimetics (e.g., ephedrine) in patients taking MAOIs. Extubation/Emergence

Reverse non-depolarizing neuromuscular blocking drugs if used

FOLLOW-UP BED ACUITY

• Standard PACU bed • AICDs must be reactivated and pacemakers reset.

ANALGESIA

Headache and myalgias can be treated with IV or PO NSAIDs or acetaminophen. COMPLICATIONS

• Anterograde and retrograde amnesia are usually limited to immediate peri-procedure memories. • Post-procedure delirium • Dental damage due to direct stimulation of masseter muscles • Skeletal fractures from inadequate neuromuscular blockade

PROGNOSIS

• ECT is more effective than pharmacotherapy in achieving remission of depression; studies have shown a 90% response rate. • Maintenance sessions are usually required at gradually increasing time intervals.

• Clinical improvement is usually evident after 3–5 sessions.

REFERENCES

1. Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: A report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol. 2009;114(3):703–713.

2. Geretsegger C, Nickel M, Judendorfer B, et al. Propofol and methohexital as anesthetic agents for electroconvulsive therapy: A randomized, double-blind comparison of electroconvulsive therapy seizure quality, therapeutic efficacy, and cognitive performance. J ECT. 2007;23(4):239–243. 3. Akcaboy ZN, Akcaboy EY, Yigitbas B, et al. Effects of remifentanil and alfentanil on seizure duration, stimulus amplitudes and recovery parameters during ECT. Acta Anaesthesiol Scand. 2005;49(8):1068–1071. 4. Gombar S, Aggarwal D, Khanna AK, et al. The bispectral encephalogram during modified electroconvulsive therapy under propofol anesthesia-relation with seizure duration and awakening. J ECT. 2011;27(2):114–118. See Also (Topic, Algorithm, Electronic Media Element) • Increased intracranial pressure • Pacemakers/ICDs • Autonomic nervous system

CODES ICD9 • 295.90 Unspecified schizophrenia, unspecified • 296.20 Major depressive affective disorder, single episode, unspecified • 296.80 Bipolar disorder, unspecified ICD10 • F20.9 Schizophrenia, unspecified • F31.9 Bipolar disorder, unspecified • F32.9 Major depressive disorder, single episode, unspecified

CLINICAL PEARLS

• Patients respond similarly to subsequent sessions of ECT, so accurate record-keeping is vital. Prior records should be checked for medications used and patient responses. • The initial ECT session often requires multiple electrical stimulations to determine seizure threshold, and this can increase the potential for parasympathetically mediated side effects such as bradycardia and asystole.

ELECTROENCEPHALOGRAM (EEG) Carsten Nadjat-Haiem, MD

BASICS DESCRIPTION

• The raw EEG is a reflection of cortical brain activity. • EEG monitoring may be utilized in the perioperative period to assess the depth of anesthesia and attainment of burst suppression, as well as indirectly monitor for cortical ischemia during surgical procedures (aneurysm clipping, carotid endarterectomy). • Analysis of the EEG requires knowledge of the differing waveforms. However, the complexity can mislead even sophisticated quantitative monitors and can lead to erroneous clinical decisions. • Modern monitors, such as the Bispectral Index (BIS) and Spectral Entropy (M-entropy), attempt to quantify this raw EEG, yielding an easy-to-interpret number. • The EEG is influenced not only by the medications administered, but also by a myriad of factors in the patient’s physiology and underlying pathology. • An accurate assessment of the depth of anesthesia via the raw EEG may reduce the incidence of awareness and improve recovery from anesthesia. PHYSIOLOGY PRINCIPLES

• Classically, patients require a full “montage” of electrodes covering the entire scalp to capture the whole spectrum of EEG generated. This is especially true when looking for regional ischemia (e.g., during carotid endarterectomy, and clipping of cerebral aneurysms) due to surgical interventions to guide further surgical decisions. • For the purpose of depth of anesthesia, monitoring 3 or 4 electrodes placed on the forehead close to the hairline will obtain an EEG sufficient to assess the depth of anesthesia (positive, negative, and reference). The rest of the scalp may be “neglected” since the frontal aspect is more resistant to pharmacologic sleep than the more posterior aspects (frontal predominance); allows for a margin of safety. • The surface electrodes pick up voltage fluctuations in the synaptic activity of the dendrites, and the sum of a large number of these is reflected in each EEG electrode. They are not specific to the voltage generated by dendritic cells, and will pick up signals generated by other, unwanted current sources such as facial, eye, and heart muscles, and electrical sources. The understanding of these noise generators is crucial in making clinical decisions. – Myogenic activity can be distinguished from the EEG by causing the waveform to “wander” above and below the baseline. Patient blinking and facial movement will cause a similar deviation from baseline and will make identification of these noise generators easy. – Muscle relaxants will eliminate the myogenic artifact. However, one must be careful to administer paralytics to patients who are only marginally asleep to avoid recall. Studies have shown that, even in the absence of myogenic artifact, the EEG is depressed by

administering paralytics. This is likely due to reduction in the afferent input to the brain from muscle spindles, slowing the EEG. – Electrical interference from line currents have a frequency of 60 Hz and are easy to detect; the highest frequency of EEG encountered is typically 30 Hz • EEG patterns (see Table 1). – Awake: High frequency and low voltage; the tracing will appear as a blurred line on the monitor. – Sedation: Loss of fast α activity and an increase in β activity. – Deep sedation: Slowing of β activity, appearance of spindle activity. Eventually, α and β activity disappears, and θ activity appears. – General anesthesia: θ waves predominate. α and β activity disappear, and with increasing depth, slow waves (Δ) predominate. – Deep levels of general anesthesia: Isoelectric EEG interrupted by “bursts” of electrical activity (burst suppression). – Further deepening of anesthesia: Increase the length spent suppressed and reduce the number of “bursts.” Eventually, isoelectricity will prevail without “bursts.” – Characteristics may not be easily evident with rapid transition between phases (i.e., during induction of general anesthesia) – Physiologic sleep and anesthetic sleep are similar, but not identical – Different anesthetic agents will produce different EEG patterns. • Physiologic sleep and anesthetic sleep are similar, but not identical. Different anesthetic agents will produce different EEG patterns.

ANATOMY

• Extrapyramidal neurons are arranged in the cerebral cortex. • Synaptic activity in the dendrites causes electrical activity, which changes over time and place. • These fluctuations in potentials in the dendritic trees of pyramidal neurons are summed up by overlying electrodes on the scalp.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Baseline EEGs in the awake patient aid with establishing “normal” and differentiating pathology intraoperatively. – Low-amplitude EEG can be drug induced, genetically determined, pathologic, or metabolic (e.g., hypoglycemia). – Healthy patients in an awake state can demonstrate very slow EEGs. – Dementia patients may display increased slow wave activity and decreased fast activity. – Schizophrenics have an increase in frontal slow waves, and a decrease in α waves. – Alcohol generally increases α waves, and severe intoxication can cause burst suppression. – Cocaine and cannabis increase α activity. – Cerebrovascular disease causes slowing. – Severe brain injury and cerebral palsy cause significant EEG slowing. • Cerebral ischemia. EEG monitoring to detect cerebral ischemia (e.g. during carotid endarterectomy, aneurysm clipping) is well established. Slowing of the EEG during a stable anesthetic and stable surgical stimulation should alert one to cerebral ischemia if the blood

pressure is marginal. • Changes in EEG pattern: Hypoglycemia, hypothermia, and hypotension will cause EEG slowing and even progress to an isoelectric EEG • Δ pattern – There may be periods of time where despite a stable level of anesthesia and no change in surgical stimulation, patients will transition to a predominately Δ pattern, indicating a very deep level of anesthesia. The cause of this is unknown, and the significance of this is also not known. One must be vigilant and pursue possible causes for this (e.g., cerebral ischemia) if this pattern persists despite lightening of anesthetic depth. – May paradoxically appear during sudden noxious stimuli; the cause remains unknown. This appearance may give the appearance of actually increasing anesthetic depth, yet the patient is actually transitioning into a lighter plane of anesthesia.

PERIOPERATIVE RELEVANCE

• The EEG can be used as a gauge of anesthetic depth and possibly reduce the risk of awareness as well as improve the recovery from anesthesia, and identify risk of cerebral ischemia. • The EEG can be used as an indicator of cerebral perfusion (e.g., during carotid endarterectomy, cerebral aneurysm clipping). Changes to look for would be a sudden slowing or isoelectricity with clamp application. • The EEG is a poor predictor of movement. There are several reasons for this. The EEG reflects cortical activity, and movement during anesthesia is not a cortical phenomenon, but controlled at deeper levels of the brain, and also at the level of the spinal cord. A patient can be judged to be “deep” yet move. The sequence of events will be that the EEG is deep, a noxious stimulus is administered to the patient, generators at the spinal cord or deep brain level will initiate patient movement, and eventually these stimuli will transition to the cortical level. The EEG will display a “lighter” level of anesthesia AFTER the patient has moved. If the brain activity is recorded in deeper structures (such as near the thalamus) a much better correlation between depth and patient movement can be obtained. • The EEG is useful in situations where patients are at greatest risk for awareness and recall. Groups at risk are traditionally trauma patients, women having emergent Cesarean sections, and patients undergoing cardiac surgery. In these scenarios, either because of the intolerance to adequate anesthesia, or the urgency for a rapid induction, patients may be at higher risk for awareness. The EEG can be an adjunct to other parameters correlating with patient depth (blink reflex, movement, blood pressure, heart rate, etc.) (3). • Barbiturates initially produce fast EEG waves, and then successively slower waves culminating in isoelectricity with increasing doses. The initial “rapid response” is only seen if very small doses are given. It is not seen with typical induction doses. • Isoflurane at subanesthetic doses will yield fast activation, and slowing of the EEG with increasing concentration. Isoflurane can produce isoelectricity. • Sevoflurane is very similar to isoflurane in its effect on the EEG, but has been observed to cause seizure-like movements at high concentrations. • Ketamine, an NMDA receptor antagonist, causes an increase in the frequency of the EEG. This may mislead the practitioner to erroneously interpret this as lighter anesthesia, and overdose the patient. This will also lead to higher numbers on quantitative EEG monitors

such as the BIS. • Nitrous oxide has a minimal effect on the EEG. Therefore, a patient on a nitrous oxide– volatile anesthetic can actually be deeper than a patient who is on a volatile anesthetic alone despite the fact that the EEG indicates the patient to be more lightly anesthetized. Nitrous oxide may also cause a decrease in the frequency of the EEG several minutes after discontinuation. • Opioids in small doses have a minimal effect on the EEG, but produce slowing at larger doses. Opioids will either slow an EEG or reduce the likelihood of movement at a stable EEG. Alfentanil may produce seizure-like activity, or unmask epileptiform foci. • Epinephrine and ephedrine can cause increasing frequencies on the EEG. • α-2 agonists, such as clonidine and dexmedetomidine, have similar effects on the EEG as barbiturates, propofol, and etomidate.

GRAPHS/FIGURES

Table 1 Summary of EEG Frequencies at Different States of Anesthesia

REFERENCES

1. Bennett C, Voss LJ, Barnard JPM, et al. Practical use of the raw electroencephalogram waveform during general anesthesia: The art and science. Anesth Analg. 2009;109(2):539– 550. 2. Avidan MS, Zhang L, Burnside BA, et al. Anesthesia awareness and the bispectral index. N Engl J Med. 2008;358(11):1097–1108. 3. Ekman A, Lindholm ML, Lenmarken C, et al. Reduction in the incidence of awareness using BIS monitoring. Acta Anaesthesiol Scand. 2004;48(1):20–26.

ADDITIONAL READING

• American Society of Anesthesiologists Task Force on Intraoperative Awareness. Practice advisory for intraoperative awareness and brain function monitoring. A report. Anesthesiology. 2006;104(4):847–864. See Also (Topic, Algorithm, Electronic Media Element)

• Burst suppression • Hypoglycemia

CLINICAL PEARLS

• The EEG is a very useful tool in judging anesthetic depth if one interprets the EEG using clinical judgment, patient factors, clinical situation, and drugs administered. • The use of quantitative EEG monitors such as the BIS cannot be advocated if they are used in a vacuum without interpreting the raw EEG and other patient factors. • The EEG is the gold standard for identifying brain ischemia. A sudden slowing of the EEG during carotid endarterectomy or cerebral aneurysm clipping has to prompt immediate reassessment of the surgical intervention. • The EEG is relatively insensitive to opioid and nitrous oxide administration, but very

sensitive to halogenated volatile agents. Therefore, a patient who is undergoing a procedure with a balanced anesthetic including nitrous oxide and an opioid is less likely to move than a patient who is receiving an exclusively volatile anesthetic at any given depth of anesthesia.

ELECTROMYOGRAPHY (EMG) Parisa Partownavid, MD

BASICS DESCRIPTION

• Electromyography (EMG) is a special type of motor monitoring that has been used intraoperatively since the mid-1970s. • It allows real-time identification and functional assessment of vulnerable nerves during surgery. Prior to its common use, surgeons relied on the Stagnara wake-up test or ankle clonus. These tests were less than ideal: They were disruptive to the surgery, potentially dangerous and traumatic to the patient, and could not be performed continually. • Additionally, perioperative nerve injuries such as ulnar nerve damage may warrant EMG evaluation. PHYSIOLOGY PRINCIPLES

• EMG is the recording of electrical muscle activity; the tracings allow interpretation as to the function of the nerve. This is similar to the electrocardiogram of the heart where electrical depolarization and repolarization can be detected by electrodes. • Electrodes are shaped as probes, needles, or wires capable of stimulating muscle contraction and/or detecting muscle activity. • Interactive software is able to process and display the electrophysiological signals as they are picked up by the recording electrodes. • Spontaneous EMG monitoring involves the placement of multiple needle electrodes into the muscle that is being examined. The EMG detects and records muscle electrical activity continually. Mechanical irritation of roots or peripheral nerves can trigger motor unit potential discharges. This aids with identifying nerves as well as inadvertent manipulation during dissection, retraction, or electrocautery use. • Evoked EMG monitoring involves placement of needle electrodes at a stimulating site (e.g., transcranially at the motor cortex [tcMEP], filum terminale) and also over peripheral muscles to record contraction. Supraphysiologic current is applied at chosen times and muscle contraction is recorded; therefore, evoked EMG assesses the integrity of the nerve fibers between the stimulating site and the muscle. PHYSIOLOGY/PATHOPHYSIOLOGY

• EMG allows for intraoperative, indirect neuromonitoring as well as aids in the diagnosis and assessment of peripheral nerve injuries. • Factors affecting change in the signal: Anesthesia, tissue temperature, surgical stage, tissue stresses, and previous pathology. Table 1 Effect of certain agents or conditions on EMG monitoring PERIOPERATIVE RELEVANCE

• Spontaneous (continuous) EMG in anesthetized patients: – The free-run EMG shows no muscle activity (a flat line), and the speaker connected to the amplifier remains silent. – Manipulation of peripheral nerves or roots (such as stretching, contusion, compression, and rubbing) results in EMG bursts called neurotonic discharges. – Mechanical irritation is translated and displayed on the monitor screen and produces a crispy noise in the speakers that provide immediate auditory feedback to the surgeon. – Limitations of the method: During surgery, it is possible to record spontaneous EMG activity not related to the intervention, such as propagated end plate potentials, fibrillations, positive sharp waves, complex repetitive discharges, fasciculation, and myokymia. This can occur in 12–16% of cases (false positives). Failure to assess non-irritative mechanisms of nerve damage such as ischemia, and remarkably sharp nerve transection (false negative) • Evoked EMG in anesthetized patients is typically in the form of motor evoked potentials (MEP) and are used to monitor nerve conduction in the anterior motor tracts of the spinal cord. – SSEPs (somatosensory evoked potentials) were initially used to assess the integrity of the dorsal column and lateral sensory tract function. However, injury to the anterior column of the spinal cord (motor fibers) will have no, or a possibly delayed, change in SSEP signals. Therefore, MEPs are employed in combination with SSEPs to afford a higher sensitivity for anterior spinal cord injury. – When motor nerve fibers are electrically stimulated, they trigger a contraction in the muscles of the corresponding myotome. The electrodes placed in these muscles record the muscle contraction as a compound muscle action potential. Evoked EMG assesses the integrity of the nerve fibers between the stimulating site and the muscle. – Any drug or physical parameter that changes impulse conduction along an axon may change the evoked potential waveform. • During head and neck surgery, the small space combined with a number of cranial nerves traversing this space can result in inadvertent nerve injury: – Parotidectomies, mastoidectomies, and acoustic neuromas: Facial nerve (VII) provides motor innervation to the muscles of facial expression, posterior belly of the digastric muscle, and stapedius muscle. Injury can result in paralysis of one side of the face, facial droop, impairment of taste, and sensitivity to sound (hyperacusis). Facial nerve monitoring involves placement of needle electrodes in the obicularis oculi and obicularis muscles that can indicate irritation of CN 7. – Thyroidectomies and parathyroidectomies: The recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN) innervate the laryngeal muscles; injury can result in vocal cord paralysis. A special endotracheal tube is utilized that can detect vocal cord movement to aid with nerve localization and detect irritation. – Radical neck dissections: The accessory nerve (XI) innervates the trapezius muscle; injury can result in shoulder dysfunction. • Neurosurgery – Tethered cord release can result in injuries to lower extremity motor neurons that

innervate the quadriceps femoris, tibialis anterior, and gastrocnemius muscles. Evoked EMG stimulates the filum terminale and anal and urethral sphincter tone are measured. – Acoustic neuroma procedures can result in damage to CN 7 and CN 8. EMG monitoring and brainstem auditory evoked potentials (BAEPs) may be implemented. BAEPs involve delivering clicks (in lieu of delivering current to stimulate muscle fibers); it is relatively resistant to anesthetic agents. • Vascular surgery – Carotid endarterectomy may use MEPs to assess for ischemia to the motor cortex from emboli or impaired perfusion during clamping. – Thoracic or abdominal aneurysm repair use MEPs to assess for spinal cord injury that can result from damage to the artery of Adamkiewicz or decreased perfusion during cross clamping. • Orthopedic surgery – Spine procedures utilize MEPs to detect direct injury to the spinal cord, nerve roots, or blood supply. • Anesthetic medications – Inhaled anesthetics decrease the waveform amplitude and increase latency. IV anesthetics have the same effect but to a lesser degree. – The best anesthetic regimen for surgery involving intraoperative monitoring is controversial. – Although total intravenous anesthesia most dependably allows signal attainment, it is often costly, requires multiple infusion pumps, and may not be easily titrated. – The safest plan is to create a stable anesthetic milieu prior to baseline signal attainment and attempt to minimize changes, particularly at critical moments where nerve injury can occur (e.g., placement of screws, dissection). – Communication regarding change in anesthetic technique or bolus administration is important. – Acceptable anesthetic agents include total IV anesthesia technique with short-acting narcotic and propofol infusion, nitrous oxide and anesthetic agents, and short-acting muscle relaxants (for induction). – Neuromuscular blocking agents and local anesthetics should be avoided. • Regional anesthesia should be avoided when intraoperative neuromonitoring is planned. • EMG can be used as a diagnostic tool following complications in regional anesthesia. Although peripheral nerve or spinal cord injury is rare, it is a significant complication of regional anesthesia. – In the event of complete or incomplete absence of nerve function beyond the duration of the anesthetic or the progression of neurologic deficit (in addition to neurosurgical consultation and radiologic imaging), electrophysiological studies such as EMG should be done. – Consideration should be given to bilateral examination and early studies to establish baseline, pre-existing lesions, and prognosis.

REFERENCES

1. Denier S. Highlights of anesthetics considerations for intraoperative neuromonitoring.

Semin Cardiothorac Vasc Anesth. 2010;14(1):51–53. 2. Dillon FX. Electromyographic (EMG) neuromonitoring in otolaryngology-head and neck surgery. Anesthesiol Clin. 2010;28:423–442. 3. Gorji R. Anesthesia and neuromuscular monitoring: Electroencephalography and evoked potentials. Available at: www.neuroanesthesia.net/ep-manual.pdf 4. Guerit JM. Neuromonitoring in the operating room, why, when and how to monitor? Electroencephalogr Clin Neurophysiol. 1998;106:1–21. 5. Liem L. Intraoperative neurophysiologic monitoring. Available at: http://emedicien.medscape.com/article/1137763-overview 6. Neal J, Bernards C, Hadzic A, et al. ASRA practice advisory on neurologic complications in regional anesthesia and pain medicine. Reg Anesth Pain Med. 2008;33(5):404–415.

7. Paradiso G, Lee G, Sarjeant R, et al. Multi-modality neurophysiological monitoring during surgery for adult tethered cord syndrome. J Neurosci. 2005;12(8):934–936. 8. Sorenson EJ. Neurologic injuries associated with regional anesthesia. Reg Anesth Pain Med. 2008;33(5):442–448. See Also (Topic, Algorithm, Electronic Media Element)

• Somatosensory and motor evoked potentials (SSEPs/MEPs) • Parathyroidectomy • Thyroidectomy

CLINICAL PEARLS

• Following the use of neuromuscular blocking agents, the return of 4 muscle twitches on train-of-four testing is sufficient to perform a consistent EMG run/recording. • Transcranial motor evoked potentials (tcMEP): Stimulation of the motor cortex through the scalp with recordings over the corresponding muscles • Cortical motor evoked potentials (cMEP): direct stimulation of the motor cortex during a craniotomy with recordings over the corresponding muscles

END STAGE LIVER DISEASE Vadim Gudzenko, MD Anahat Dhillon, MD

BASICS DESCRIPTION

End-stage liver disease (ESLD) is usually manifested by cirrhosis of the liver (fibronodular hyperplasia and bridging fibrosis). Functionally, ESLD is characterized by impaired synthetic function, cholestasis, and portal hypertension (1).

EPIDEMIOLOGY Prevalence

Exact prevalence is unknown, but it is estimated that 0.15% of the population has liver cirrhosis. Mortality

Perioperative mortality in patients with cirrhosis varies from 8.3% to 25% depending on the severity of disease and type of surgery (2). ETIOLOGY/RISK FACTORS

Viral hepatitis (primarily B and C), alcohol abuse, autoimmune conditions, drug reactions, cholestasis, genetic metabolic aberrations, and inflammatory disease of bile tracts PHYSIOLOGY/PATHOPHYSIOLOGY

• Impaired synthetic function. Fibronodular hyperplasia and bridging fibrosis cause damage to hepatocellular units; consequently, glycogenolysis, gluconeogenesis, protein synthesis, and metabolism of byproducts/medications are impaired. This manifests clinically as decreased albumin production, malnutrition, muscle wasting, coagulopathy, cholestasis, and bilirubinemia. • Portal hypertension. Fibronodular hyperplasia and fibrosis also cause sinusoidal obliteration and prevent effective portal venous blood flow. This results in venous congestion of the spleen (platelet sequestration), small bowel, and colon as well as esophageal varices and gastropathy from accessory drainage along the diaphragm, mediastinum, and esophagus. Portal hypertension in combination with hypoalbuminemia cause ascites and pleural effusions. • Coagulopathy. General malnutrition, poor absorption of vitamin K (secondary to severe cholestasis), and impaired synthesis of coagulation factors result in impaired coagulation (1).

ANESTHETIC GOALS/GUIDING PRINCIPLES

Assessment of concomitant organ dysfunction and optimization. Patients have an increased

risk of morbidity and mortality.

PREOPERATIVE ASSESSMENT SYMPTOMS

Malaise and fatigue, jaundice, loss of appetite, itching, and bruising History

• Risk factors: Alcohol abuse, illicit drug use, and a history of blood transfusions • Family history of jaundice, anemia, or hereditary liver disease • In a patient with confirmed liver cirrhosis, assess for the presence of ascites or edema, severity of encephalopathy, and variceal bleeding.

Signs/Physical Exam

Temporal wasting, jaundice, spider nevi, gynecomastia, testicular atrophy, ascites, hepatomegaly, palmar erythema, and asterixis (3)

TREATMENT HISTORY

Transjugular intrahepatic portosystemic shunt (TIPS), esophageal banding, and paracentesis MEDICATIONS

• Lactulose, rifaximin, and neomycin are taken for management of hepatic encephalopathy. • Furosemide and spironolactone are used for the management of ascites. • Non-selective beta blockers (propranolol and nadolol) are used for control of portal hypertension and prevention of variceal bleeding. • Octreotide, a splanchnic vasoconstrictor, is used for acute variceal bleeding.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Routine screening labs in patients without risk factors, history, or suspicion of liver disease are not recommended. • For a patient with an established diagnosis of ESLD/cirrhosis: – CBC with platelet count, creatinine, coagulation panel (PT/INR, PTT), LFTs (ALT, AST, and bilirubin), and albumin – Transthoracic echocardiography to evaluate for the presence of pulmonary hypertension and cardiomyopathy

CONCOMITANT ORGAN DYSFUNCTION

• Hepatic encephalopathy is a spectrum of neuropsychiatric conditions varying from mild confusion to deep coma; the exact mechanism is unknown. It can be precipitated by infection, GI bleeding, hypoxia, azotemia, and other stressful states. Elevated levels of ammonia are associated with encephalopathy; however, the level does not have a direct correlation with severity (1,2). • Pulmonary dysfunction (hepatopulmonary syndrome) from intrapulmonary arteriovenous shunts can result in hypoxia. Hallmarks include orthodeoxia and platypnea (desaturation

and dyspnea in the supine position). • Renal dysfunction (hepatorenal syndrome): Develops with advanced portal hypertension and is associated with profound splanchnic vasodilatation, leading to decreased renal perfusion and renal insufficiency. Hepatorenal syndrome is usually reversible after liver transplantation.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Child–Turcotte–Pugh (CTP) scores: Elective surgery for class A is well tolerated, class B is permissible with optimization, and class C should not be considered for elective surgery due to prohibitively high perioperative mortality (1). • Ascites increases the risk for perioperative pulmonary complications, postoperative wound infection, and dehiscence. Moderate-to-severe ascites can be treated with large volume paracentesis and intravenous administration of albumin (4). • Worsening hepatic encephalopathy should be optimized with medical therapy (lactulose, rifaximin, or neomycin) before elective surgery. • Coagulopathy and thrombocytopenia should be corrected before major surgery to decrease the risk of major bleeding, but transfusion of large volumes of FFP might be detrimental secondary to volume overload.

CLASSIFICATIONS

• CTP class includes 2 clinical signs (ascites and encephalopathy) and 3 lab values (albumin, bilirubin, and PT/INR). Combination of points for each feature defines class: A—mild, B— moderate, and C—severe (1,4). • MELD score (Model for End-stage Liver Disease) takes into account creatinine, bilirubin, and INR and was originally devised as a prognostic tool of short-term mortality of patients with cirrhosis undergoing TIPS procedure. MELD has been validated as a predictor of perioperative morbidity and mortality for a variety of surgeries. Higher scores (>14) are correlated with high perioperative mortality. In 2002, the United Network for Organ Sharing (UNOS) adopted MELD for donor liver allocation (3).

TREATMENT PREOPERATIVE PREPARATION Premedications

• Parenteral vitamin K should be considered. • FFP, platelets, and cryoprecipitate are used to correct coagulopathy and thrombocytopenia. • Benzodiazepines and opioids should be used judiciously because the metabolism of midazolam, diazepam, and morphine is significantly impaired and can worsen encephalopathy (2).

INTRAOPERATIVE CARE Choice of Anesthesia

• Regional anesthesia may be considered if coagulopathy is not present.

• General anesthesia with an ETT is typically preferred when there is increased risk of aspiration. • Monitored anesthesia care should be considered whenever appropriate for the procedure.

Monitors

• Arterial line for monitoring blood pressure, blood sugars, and acidosis may be needed. • Central venous catheters have been shown to be safe with coagulopathy and may be necessary when large volumes of fluid resuscitation are anticipated (to guide and avoid over-resuscitation which can lead to further liver damage). Ultrasound placement may reduce inadvertent arterial injury. • Transesophageal echocardiography should be used with extreme caution due to the risk of rupturing esophageal and gastric varices.

Induction/Airway Management •

Rapid-sequence induction with succinylcholine is most commonly used. Pseudocholinesterase levels may be decreased resulting in a prolonged duration of paralysis. • Induction agents should be titrated slowly and to effect due to altered pharmacokinetics/ pharmacodynamics (increased volume of distribution, decreased protein binding, decreased clearance, increased hemodynamic and central nervous system sensitivity). • Nasotracheal intubation or nasal airway manipulation should be done with extreme caution.

Maintenance

• Maintenance agents: Typically volatile agent +/– nitrous oxide with the goal of maintaining hemodynamics and MAP within baseline. Cirrhotic liver is extremely susceptible to ischemic injury in the setting of even mild hypotension. Modern volatile anesthetics (desflurane and sevoflurane) do not directly affect hepatic perfusion (unlike halothane which significantly reduces hepatic artery blood flow). • Although single doses of induction agents such as etomidate, propofol, and methohexital have similar pharmacokinetic properties in ESLD, recovery from propofol infusion might be prolonged. • Morphine and meperidine (primarily metabolized by the liver) can prolong encephalopathy. Pharmacokinetics of fentanyl and its derivatives (alfentanil and sufentanil) are less affected. • Steroidal muscle relaxants (vecuronium, rocuronium, and pancuronium) have an increased volume of distribution that requires higher induction dosing. If primarily metabolized by the liver, the duration of action may be prolonged. Atracurium and cisatracurium, which are metabolized by plasma esterases, are not affected in ESLD.

Extubation/Emergence

Determined by preoperative liver function, type of surgery, and medications administered. Patients with ESLD are at increased risk for prolonged emergence.

FOLLOW-UP BED ACUITY

Monitored floor or ICU management should be considered in CTP class B and C or following

major surgery.

MEDICATIONS/LAB STUDIES/CONSULTS

• Sedatives and pain medications that are predominantly metabolized by the liver should be avoided because they can precipitate and exacerbate hepatic encephalopathy. • Maintaining cardiovascular stability is crucial to maintain hepatic perfusion. • Venous pressure should be maintained on the lower side to avoid venous congestion of liver. If using CVP monitoring, keep CVP <10 mm Hg. • Early nutrition is extremely important in recovery of intestinal and hepatic function. Enteral nutrition is preferable. • Probability of perioperative renal failure is increased; therefore maintaining stable renal perfusion is key. Renal protective strategies, such as dopamine, nesiritide, fenoldopam infusion, or mucomyst, have not shown improved outcomes in clinical trials. • Low threshold for antibiotic administration should be used since patients with ESLD are susceptible to infections and are at increased risk for perioperative sepsis and wound infections. • Coagulopathy and thrombocytopenia should be corrected aggressively.

COMPLICATIONS

• Most common: Hemorrhage, sepsis, liver failure, fluid overload, and hepatorenal syndrome. • Surgical wound complications include infection, dehiscence, fistula, abscess, and surgical site bleeding. • General complications include pneumonia/ARDS, ventilation dependence, chronic heart failure, arrhythmia, myocardial infarction, urinary tract infections, paralytic ileus, pulmonary embolism, and death (2).

REFERENCES

1. Wiklund RA. Preoperative preparation of patients with advanced liver disease. Crit Care Med. 2004;32(Suppl 4):S106–S115. 2. Hanje AJ, Patel T. Preoperative evaluation of patients with liver disease. Nat Clin Pract Gastroenterol Hepatol. 2007;4(5):266–276. 3. Millwala F, Nguyen GC, Thuluvath PJ. Outcomes of patients with cirrhosis undergoing non-hepatic surgery: Risk assessment and management. World J Gastroenterol. 2007;13(30):4056–4063. 4. Ziser A, Plevak DJ. Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery. Curr Opin Anaesthesiol. 2001;14(6):707–711.

ADDITIONAL READING

• Ginès P, Cárdenas A, Arroyo V, et al. Management of cirrhosis and ascites. N Engl J Med. 2004;350(16):1646–1654. • Hemprich U, Papadakos PJ, Lachmann B. Respiratory failure and hypoxemia in the cirrhotic patient including hepatopulmonary syndrome. Curr Opin Anaesthesiol. 2010;23(2):133– 138.

• Meltzer J, Brentjens TE. Renal failure in patients with cirrhosis: Hepatorenal syndrome and renal support strategies. Curr Opin Anaesthesiol. 2010;23(2):139–144. • Ramsay M. Portopulmonary hypertension and right heart failure in patients with cirrhosis. Curr Opin Anaesthesiol. 2010;23(2):145–150.

See Also (Topic, Algorithm, Electronic Media Element) • Cirrhosis • Postoperative jaundice

CODES ICD9

• 571.5 Cirrhosis of liver without mention of alcohol • 573.9 Unspecified disorder of liver ICD10 • K74.60 Unspecified cirrhosis of liver • K76.9 Liver disease, unspecified

CLINICAL PEARLS

• Perioperative mortality after abdominal surgery in patients with CTP class C is 70–80%. Emergent surgery is an independent risk factor of mortality. • Acute liver failure might develop on postoperative day 2 or 3 in patients with stable liver disease secondary to perioperative hepatic hypoperfusion. • Perioperative fluid overload is detrimental due to an increase in venous pressure and venous congestion which leads to hepatic hypoperfusion.

END TIDAL CARBON DIOXIDE (ETCO2) Siamak Rahman, MD

BASICS DESCRIPTION

• ETCO2 is the partial pressure or maximal concentration of carbon dioxide (CO2) at the end

of an exhaled breath; it is expressed as a percentage of CO2 or mm Hg. Normal values are 5– 6% CO2, which is equivalent to 35–45 mm Hg. A capnogram is the ETCO2 plotted against

time. • ETCO2 is used as a noninvasive estimate of alveolar and hence arterial carbon dioxide

partial pressures (or percentages). This is based on 2 assumptions: – ETCO2 is approximately 4–5 mm Hg lower than PaCO2 in the awake state. This normal

gap signifies the magnitude of the physiological dead space (sum of the anatomical and alveolar dead spaces). – A change in one causes an equal change in the other, in the same direction, thus leading to a constant gradient. • Pathological or apparatus dead space can further increase the gap between ETCO2 and PaCO2.

• As recommended by the ASA House of Delegates, the adequacy of ventilation shall be evaluated by continual observation of qualitative clinical signs and ETCO2 monitoring when

endotracheal tube or laryngeal mask airway is used as well as during moderate or deep sedation unless precluded or invalidated by the nature of the patient, procedure, or equipment.

PHYSIOLOGY PRINCIPLES

• CO2 elimination depends upon 3 interrelated variables. If 2 of these variables are held constant, any change in ETCO2 reflects an alteration in the third variable: – CO2 production

– Alveolar ventilation – Cardiac output • Monitoring of end-tidal carbon dioxide tension (ETCO2) is routinely used in different fields of medicine (emergency medicine, anesthesiology, and critical care medicine). • ETCO2 monitors are either semi-quantitative changes (relies on changes in pH and color of

the paper) or quantitative changes (based on infrared absorption of the light passing through the gas). The quantitative method uses either in-line measurement or a side stream sampling of the exhaled air. The measured ETCO2 in non-intubated patients (side stream

sampling technique) via a nasal cannula or an oxygen mask is a sign of breathing. It may

also correlate to the actual ETCO2, depending on the device used to deliver oxygen and the

flow of oxygen. • Capnogram is the ETCO2 plotted against time.

– Phase I (a→b): Inspiration and the first portion of exhalation (gas from large airways). Under normal circumstances, there is no CO2 during inspiration, and during the beginning of exhalation, gas from the large airways empties first (devoid of CO2).

– Phase II (b→c): Expiration continues and marks the transition between airway and alveolar gas. CO2 is seen as a rapid upstroke toward the alveolar plateau.

– Phase III (c→d): Expiration of alveolar gas, known as the alveolar plateau. Under normal circumstances, it is flat. – Phase IV (d→e): Onset of inspiration and represented as a down slope. Of note, the ETCO2 value is the highest value, and often measured at the d point.

Normal capnogram

ANATOMY

• ETCO2 sampling monitors locations.

– Distal: Decreased dead space, resulting in decreased gap. Cardiac oscillations are often smoothed over when the sampling port is more distal to the airways (deeper tracheal or bronchial areas).

DISEASE/PATHOPHYSIOLOGY • CO2 production:

– Decreased production, and hence ETCO2, may be seen with hypothermia.

– Increased production, and hence ETCO2, may be seen with hypermetabolic states such as

malignant hyperthermia, thyroid storm, fever, sepsis, or shivering. • Alveolar ventilation: – Decreased minute ventilation, and hence ETCO2, may be seen with inadequate ventilator

settings, or in spontaneously ventilating patients with narcotics, residual paralysis, metabolic alkalosis, or other IV or volatile anesthetic agents, affecting tidal volume and/or

respiratory rate. – Increased minute ventilation, and hence ETCO2, may be seen with inadequate ventilator

settings, pain, metabolic acidosis, or awareness under anesthesia. – Atelectasis and other situations in which the alveoli are perfused, but not ventilated (pneumonia, mucus plug, and pulmonary edema), have little effect on ETCO2 because CO2 is highly soluble and will diffuse out almost completely in better ventilated alveoli. Thus, shunting has only a minor effect on the ETCO2 and PaCO2 gradient.

– Airway obstruction can result from bronchospasm, upper airway obstruction, biting, or excessive mucus production. The capnogram may demonstrate a delayed alveolar emptying with a slow rise of expired CO2, leading to failure to obtain a true plateau (sloping of phase II). It does not normally change the ETCO2 value.

• Cardiac output: ETCO2 can function as an indicator of profound hypotension and cardiac

arrest. Dead space ventilation results in V/Q mismatching secondary to impaired pulmonary blood flow and exhalation of CO2. Thus, despite decreases in the ETCO2, the PaCO2

continues to rise, resulting in an increased gap. – During cardiac arrest, the ETCO2 falls close to zero; when cardiopulmonary resuscitation starts, the ETCO2 increases and correlates to pulmonary blood flow.

– Pulmonary emboli from air, clot, fat, or amniotic fluid also impair pulmonary blood flow, and a decreased ETCO2 can signal this occurrence (low specificity). PERIOPERATIVE RELEVANCE

• Endotracheal tube placement confirmation is the most common use of ETCO2 detection. This is done by a calorimetric ETCO2 detector in emergency situations and outside of the operating room. After esophageal intubation, ETCO2 may be initially detected but will taper off; thus, sustained ETCO2 should be noted over several breaths.

• Hypoventilation and obstruction during spontaneous breathing and sedation cases can be detected early with ETCO2.

• Circuit disconnect: In addition to low-pressure alarms which are often used to detect the drop in peak inspiratory pressure (PIP) that occurs when a patient becomes disconnected from a ventilator, lack of ETCO2 detection could be a sign of circuit disconnect. • Diaphragmatic paralysis: Curare notch is the early sign of reversal of muscle paralysis.

Curare notch, diaphragmatic movement, or attempted spontaneous ventilation

Phase I second elevation can represent diaphragmatic efforts or attempted breaths

• Malignant hyperthermia: Early detection is of utmost importance, and a rise in ETCO2 is one of the earliest signs. ETCO2 trends could also be efficacious in monitoring the treatment.

• Elevated baseline or partial rebreathing represents CO2 in the inspired gas. The return of

ETCO2 close to zero depends mostly on the proper functioning of the breathing circuit,

valves, and CO2 absorber. Abnormalities may be seen with a low fresh gas flow, faulty

expiratory valve, and exhausted CO2 absorber.

Phase I elevated, with Phase III sloping signifies increasing inspired CO2 and expired CO2. Can be seen when the absorbent

is depleted or faulty unidirectional valve

• Cardiogenic oscillations: Synchronous changes in pulmonary blood flow during slow expiration and mechanical agitation of different lung regions induced by cardiac activity and pulmonary blood flow contribute to the creation of ripples. This is often observed in a repetitive pattern during the alveolar plateau in synchrony with the heartbeat.

Cardiac oscillations that will correlate to heart rate

• Sudden loss of ETCO2 waveform during anesthesia could be due to a lack of respiratory effort, airway obstruction, unintentional extubation, or circuit disconnect.

Decreasing ETCO2 with each breath may be seen with esophageal intubation, profound hypotension, or cardiac arrest

• Profound hypotension: In addition to palpating a pulse, rechecking noninvasive blood pressure cuff, a sudden decrease in the ETCO2 can be a useful tool to confirm the diagnosis of low cardiac output and allow for early treatment. • Mechanical forces during thoracic or abdominal surgery may be seen during phase 1.

Phase I irregularities may be seen with mechanical forces on the thorax or abdomen that get transmitted as tiny oscillation to the end of the endotracheal tube

REFERENCE

1. Dubin A, Murias G, Estenssoro E, et al. End-tidal CO2 pressure determinants during hemorrhagic shock. Intensive Care Med. 2000;26(11):1619–1623.

ADDITIONAL READING

• American Society of Anesthesiologists. Standards for basic anesthetic monitoring. Available at: http://www.asahq.org/ See Also (Topic, Algorithm, Electronic Media Element) • Dead space • Venous air embolism • Malignant hyperthermia • Pulmonary ventilation and perfusion matching • Cardiac output

CLINICAL PEARLS

• End-tidal CO2 is the partial pressure of CO2 at the end of expiration during tidal breathing. It is assumed to be representative of alveolar gas but it is lower than alveolar PCO2 (the

alveolar dead space dilutes and lowers the end-tidal PCO2).

• Mixed expired PCO2 (PETCO2) is the partial pressure of CO2 in the expired gas during a tidal breath. It is much lower than ETCO2 because the CO2-free gas from anatomical dead space

dilutes even further. • There is only a subtle difference between PETCO2 and ETCO2 so ETCO2 is a valid substitute for PETCO2.

ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP) Basavana G. Goudra, MD, FRCA, FCARCSI Vinay Chandrasekhara, MD

BASICS DESCRIPTION General

• Endoscopic retrograde cholangiography (ERCP) is a diagnostic and therapeutic procedure performed with a flexible endoscope and fluoroscopy to examine the biliary tree and/or the pancreatic ducts. • Indications include obstructive jaundice due to common bile duct stones/strictures, papillary stenosis, or a pancreatic head mass. It is also indicated for the treatment of pancreatic duct abnormalities associated with recurrent or chronic pancreatitis (pancreatic duct strictures or stones), bile duct and pancreatic duct leaks (either traumatic or iatrogenic), cholangitis (infection of the bile duct from prolonged biliary stasis), and for evaluation of ampullary tumors. • A side-viewing endoscope is inserted through the mouth into the second portion of the duodenum where the major papilla is identified. Using a catheter with or without the assistance of a guidewire, the duct of choice (biliary, pancreatic, or both) is cannulated. The duct(s) are visualized by injecting contrast dye along with simultaneous fluoroscopy. • Based on the findings, a variety of therapeutic procedures can be performed. Endoscopic sphincterotomy or cutting of the sphincter of Oddi muscle is routinely performed to allow for improved drainage and flow of bile and pancreatic secretions. Additionally, stents can be placed either in the biliary or in the pancreatic duct to facilitate drainage. Biliary stones can be extracted with the use of a balloon catheter or a basket or can be crushed with a mechanical lithotriptor. Position

• Usually prone with the head laterally rotated to the left • Occasionally lateral or supine if the patient is unable to tolerate the prone position (comorbidities, recent abdominal surgery) Approximate Time

30–60 minutes, depending on the endoscopist’s experience and the procedural indication EBL Expected None

Hospital Stay

• Can be performed in an outpatient setting; hospital stays are not mandated unless a

complication arises. • May be performed for inpatients as a semi-urgent procedure. These patients are often ASA 3 or 4 and may present with complex hepatobiliary issues or sepsis due to cholangitis.

Special Equipment for Surgery

May include guidewires, exchange platforms, stone extraction devices, biliary and pancreatic stents and dilators EPIDEMIOLOGY Incidence

• Gallstone disease is estimated to affect >20 million adults in the US at an annual cost of $6.2 billion (1). • 5–10% of those undergoing laparoscopic cholecystectomy for symptomatic cholelithiasis and 18–33% of patients with acute biliary pancreatitis will also have choledocholithiasis (2). • Pancreatic cancer is the 10th most common site of new cancer, but is the 4th leading cause of cancer death in the US and worldwide.

Prevalence

• An estimated 1.41% of men and women will be diagnosed with cancer of the pancreas; in 2010 an estimated 43,140 new cases were diagnosed in the US, accounting for 2.8% of all cancers (3). • Roughly 2,000–3,000 new cases of extrahepatic cholangiocarcinomas are diagnosed in the US each year.

Morbidity

Low; can include bleeding, cholangitis, perforation, and pancreatitis Mortality

The overall mortality related to complications from ERCP is 0.6%. ANESTHETIC GOALS/GUIDING PRINCIPLES

• ERCPs present a unique challenge to the anesthesia provider: – They are often performed in an out-of-OR location. – Patients often lack a secure airway and are expected to maintain spontaneous ventilation (SV). – The airway is shared with the endoscopist. – Patients are in the prone position. – IV anesthetic techniques are implemented. – The intensity of stimulation could be similar to minor surgery. • Multiple IV techniques may be utilized with a goal of maintaining spontaneous ventilation and hemodynamic stability while rendering the patient unresponsive to stimulation. • Significant liver disease requires dosing modification since it can affect the volume of distribution, have prolonged duration of action (hepatically cleared drugs), and increase the availability of free (active) drug (decreases in albumin and other plasma proteins). • Unlike intravenous administration of contrast, injection of contrast into the bile duct or

pancreatic duct is not commonly associated with renal failure and does not require preprocedural creatinine levels to be checked.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Abdominal or back pain • Jaundice • Loss of weight • Cachexia • Ascites • Psychological anxiety, depression

History

• Recent or planned cholecystectomy, bile leak • Weight loss, jaundice, abdomen and back pain if pancreatic mass or cholangiocarcinoma is suspected • Recent pancreatitis, gallstones, alcohol use, chronic pancreatitis • Liver transplant • Primary sclerosing cholangitis • Hepatitis B or C

Signs/Physical Exam

• Charcot’s triad of cholangitis: Jaundice, fever, right upper quadrant pain • Evaluate for signs of chronic liver disease • Airway exam must be performed in the event that the airway needs to be supported or secured.

MEDICATIONS

Recent or chronic opioid use may increase anesthetic requirements. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

Liver function tests and markers of hepatic function (INR, platelet count) CONCOMITANT ORGAN DYSFUNCTION

• Hepatic decompensation leading to encephalopathy, renal failure, or cardiopulmonary compromise may occur. • Pancreatic insufficiency

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics may be appropriate. • Analgesics may be considered for patients with acute or chronic pain.

Special Concerns for Informed Consent

• Risk of aspiration, sepsis, bleeding from airway interventions • Discuss deep sedation and realistic goals. Patients are not typically going to be “knocked out.”

Antibiotics/Common Organisms

Coverage for biliary infections may be required for patients with cholangitis or persistent biliary obstruction. Typical antibiotics include fluoroquinolones with or without metronidazole or a combination of beta-lactam/beta-lactamase inhibitor (e.g., ampicillin– sulbactam or piperacillin–tazobactam). INTRAOPERATIVE CARE Choice of Anesthesia

• Deep sedation is commonly preferred with a total IV technique. Although frequently considered as “MAC,” as the patient neither recalls nor responds to the procedural stimulation, it can also be classified as general anesthesia and consented as such. Propofol is commonly used in combination 1. with a potent opioid or ketamine with titration to SV. • General endotracheal anesthesia is used infrequently and is dependent on the anesthesia provider’s comfort with the patient’s airway (e.g., Mallampati 4, risk of aspiration, morbid obesity) as well as difficulty and anticipated length of the procedure.

Monitors

• Standard ASA monitors • In sick inpatients, continue invasive monitoring, if already established.

Induction/Airway Management

– Deep sedation with propofol and fentanyl – Nasal trumpets may be inserted to provide a conduit (bypasses oropharynx and endoscope) to deliver an FIO2 of 1.0 at high flows into the hypopharynx.

By using an endotracheal tube connector and Mapleson C or other portable circuit, one can provide some degree of positive pressure ventilation when the endoscope is in situ. • A jet ventilator can be used supraglottically to provide intermittent or continuous highfrequency ventilation. This would allow maintenance of oxygenation and permits deeper sedation. • General endotracheal anesthesia is induced in standard manner, in the supine position, after appropriate pre-oxygenation. Consider a rapid-sequence induction, as appropriate. After confirming tube location and securing it appropriately, the patient is positioned, with careful attention to pressure points.

Maintenance

• Deep sedation: A multitude of regimens exist, often with propofol at the core. When supplemented, a reduction in dosing should be anticipated. Although the anesthetic drugs

may be combined in the same syringe or bag, this limits the ability to titrate one medication upwards or downwards. – Propofol is a GABA receptor agonist that provides sedation; at higher doses it can result in loss of consciousness and amnesia. However, it has a 300% pharmacokinetic and pharmacodynamic variability, can lead to unanticipated apnea, and does not provide analgesia (or amnesia reliably). – Ketamine provides analgesia while maintaining SV. However, it can cause tachycardia, excessive salivation (which can provoke laryngospasm), and emergence phenomenon. – Remifentanil is a potent analgesic (mu receptor). However, respiratory depression, bradycardia, nausea/vomiting, and chest wall rigidity limit its use as a sole drug in endoscopy. – Dexmedetomidine can provide sedation and analgesia. However, its use in the endoscopy suite is limited due to its long onset time and increased duration of action. Additionally, it can cause intense bradycardia and hypotension. • Titration to effect at various levels of stimulation while maintaining a spontaneously ventilating patient is more important than the drug or technique used.

Extubation/Emergence

With the use of potent, short-term hypnotics and opioids, patients usually “wake up” within 5–7 minutes after termination of the anesthetic. The use of longer-acting medications or decreased drug clearance capacity can prolong the time to emergence.

POSTOPERATIVE CARE BED ACUITY

• Most are performed on an outpatient basis. • Comorbid conditions and vital signs should dictate the level of care for inpatients.

ANALGESIA

Not typically needed COMPLICATIONS

• Common surgical complications: – Bleeding – Infection – Perforation – Pancreatitis – Cramps in the abdomen usually disappear after the gas used for insufflation is absorbed. • Common anesthetic complications: – Postoperative nausea and vomiting – Respiratory depression, hypoxia, desaturation.

REFERENCES

1. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States. Part 1: Overall and

upper gastrointestinal diseases. Gastroenterology. 2009;136:376–386. 2. ASGE Standards of Practice Committee. The role of endoscopy in the evaluation of suspected choledocholithiasis. Gastrointest Endosc. 2010;71:1–9. 3. merican Cancer Society. Cancer facts & figures. Atlanta: American Cancer Society, 2010.

ADDITIONAL READING

• Adler DG, Baron TH, Davila RE, et al. ASGE guideline: The role of ERCP in diseases of the biliary tract and pancreas. Gastrointest Endosc. 2005;62:1–8. See Also (Topic, Algorithm, Electronic Media Element)

• Colonoscopy • End stage liver disease • Cholecystectomy

CLINICAL PEARLS

• Nasal trumpet contraindications include antiplatelet medications and coagulopathies from liver disease. • Given the extended procedure duration and need for deeper levels of sedation compared to other routine endoscopic procedures, most centers rely on an anesthesia care team-directed propofol sedation rather than IV conscious sedation.

ENDOSCOPIC SINUS SURGERY Shannon M. Gossett-Popovich, MD

BASICS DESCRIPTION General

• Also known as FESS (functional endoscopic sinus surgery). It serves as a diagnostic and therapeutic procedure in which limited surgical intervention can improve ventilation and drainage of the ostiomeatal complex (also known as the “Messerklinger technique”). – Indications include: Chronic sinus infection refractory to medical management Recurrent sinusitis Nasal polyposis Control of epistaxis Sinus mucoceles Excision of nasal tumors – Involves insertion of a rigid, nasal endoscope into the nose for direct visualization of the sinus openings – The procedure allows for removal of tissue obstructing the ostiomeatal complex, allowing for drainage of mucus, while protecting normal, non-obstructing anatomy and mucous membranes. • Other indications include: – Skull base surgery CSF leak closure Endoscopic pituitary surgery – Orbital surgery Orbital decompression Dacryocystorhinostomy Optic nerve decompression Position

• Supine with the bed at a 90° or 180° position. • Reverse Trendelenburg with the head up 30–40° to allow for decreased arterial pressure and prevention of venous congestion (improves surgical conditions and decreases blood loss). There is a potential risk of venous air embolism in the head-up position during ESS.

Incision

Endoscope inserted into the nose. It is a minimally invasive technique that alllows for a thorough examination of the nose from the anterior nare to the postnasal space. Approximate Time

1–3 hours

EBL Expected 100–300 mL

Hospital Stay

Outpatient or overnight hospital stay Special Equipment for Surgery

• Rigid fiberoptic nasal endoscope • Vasoconstricting agents (cocaine or local anesthetic solution with epinephrine) aid in decreasing bleeding in the surgical field. • Intraoperative image-guidance systems

EPIDEMIOLOGY Prevalence

Sinusitis is a very common condition (31 million Americans affected each year). Prevalence

Increased likelihood of surgical intervention needed in patients with a history of asthma, allergic disorders, deviated nasal septum, and previous nasal surgery Morbidity

Major complications: 0.44% incidence (versus 1.4% in non-endoscopic procedures). CSF leaks comprise almost half of all major complications (0.2%). Mortality

Extremely low risk of death

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The airway should be protected from contamination. • Adequately addressing postoperative pain and avoiding postoperative nausea and vomiting can facilitate expeditious recovery and discharge. • Provide optimal surgical conditions and minimize risk of bleeding

PREOPERATIVE ASSESSMENT SYMPTOMS

Chronic sinusitis, nasal polyps, epistaxis, olfactory disturbances, nasal obstruction, postnasal discharge, headaches, mid-facial pain History

• Previous nasal surgery, nasal polyps, deviated nasal septum • Asthma, allergic disorders • Active infection/inflammation

• Gastroesophageal reflux disease (GERD) • Presence of vascular tumors

Signs/Physical Exam

• Head and neck exam: Airway/nasal abnormalities • Cardiopulmonary exam: Wheezing, breathing obstruction

MEDICATIONS

• Preoperative steroids can improve operating conditions in patients with rhinosinusitis and polyposis. • Preoperative antibiotics may be considered to decrease infection and inflammation. • Medications that increase the risk of perioperative bleeding (anticoagulation and antiplatelet drugs) should be withheld prior to surgery (but the risks of stopping these should be carefully considered given the patient’s history). – Aspirin, NSAIDs, vitamin E, ginkgo biloba, ginseng, and garlic should be withheld 7 days prior to surgery.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC, PT/PTT, INR, Type & Screen • CT scan of the sinuses to identify disease extent and pathological tissue (aids in surgical planning) • Radiographic embolization of vascular tumors should be considered, if present, to decrease the risk of bleeding. CONCOMITANT ORGAN DYSFUNCTION Pulmonary disorders

TREATMENT PREOPERATIVE PREPARATION Premedications

Vasoconstriction, with cocaine or a local anesthetic with epinephrine, is administered by the surgeon prior to endoscopy to decrease blood flow to the nasal sinus tissue. Special Concerns for Informed Consent

While unlikely, it may be prudent to obtain consent for possible blood transfusion if deemed necessary during the procedure. Antibiotics/Common Organisms

• Cephalosporins are chosen most commonly to provide Staphylococcus coverage. • 57% of surgeons preferred antibiotic prophylaxis, despite lack of solid evidence to support use of prophylactic antibiotics.

INTRAOPERATIVE CARE Choice of Anesthesia

• Local anesthesia with mild sedative: Careful patient selection is necessary and extreme caution should be used due to blood/secretions that may accumulate in the airway. • General anesthesia with an endotracheal tube (ETT) or laryngeal mask airway (LMA)

Monitors

• Standard ASA monitors: A noninvasive BP cuff is usually adequate unless the patient’s comorbidities necessitate an arterial line. • One large-bore, well-functioning IV • Eyes should remain uncovered during surgery. Surgeon will continually monitor for orbital swelling, afferent papillary defect, or eyelid bruising.

Induction/Airway Management

• Slow controlled induction (unless the patient requires rapid-sequence induction) • ETT versus LMA – ETT requires higher anesthetic depth to maintain a target BP. Local anesthetic can be applied to the vocal cords prior to intubation to decrease the risk of postoperative laryngospasm. Avoid tight ETT ties; minimize positive end expiratory pressure to keep the central venous pressure and venous congestion at a minimum. – LMA provides excellent operating conditions. It allows for decreased sympathetic stimulation on insertion, protects the upper airway from contamination, and allows for smoother emergence. It will not, however, protect against regurgitation; thus, contraindications include hiatal hernia, GERD, obesity, and a full stomach.

Maintenance

• Total intravenous anesthesia (TIVA): Propofol and remifentanil are commonly utilized as they are easily titratable to HR and BP goals and provide a smooth and rapid emergence. Remifentanil has the benefit of providing hemodynamic stability, while inducing slight hypotension. It lowers BP via decreasing cardiac output without peripheral vasodilation. However, it can cause PONV. • Neuromuscular blockade can be used as needed to facilitate placement of the ETT and/or positive pressure ventilation. • Fluids should be administered with caution and care to avoid overloading the patient, raising the BP, and allowing for controlled hypotension if the patient is a good candidate for this method of anesthesia. • Consider controlled hypotension methods to decrease blood loss and improve surgical conditions. – A preoperative dose of alpha-2 agonist clonidine (5 mcg/kg) may be helpful in some patients. – Vasodilating agents that decrease systemic vascular resistance (SVR) and lower mean arterial pressure (MAP) <50 mm Hg have been shown to improve surgical conditions. – Bradycardia has been found to improve surgical conditions. Decreasing heart rate with a short acting beta-blocking drug such as esmolol can provide better surgical conditions

than a vasodilator that decreases the mean arterial pressure. – Controlled hypotension should be used with caution: 0.6% risk of ischemic organ failure. • Antiemetic administration intraoperatively is recommended to reduce PONV and should be chosen based on the suitability to each patient.

Extubation/Emergence

• Blood and secretions may be present in the airway and should be thoroughly cleared. • Avoid coughing and straining which can lead to venous engorgement and bleeding. • Laryngospasm can lead to negative pressure pulmonary edema. • Ideally wait until airway reflexes have completely returned prior to extubation.

FOLLOW-UP BED ACUITY

Ambulatory surgery or overnight hospital observation if significant blood loss or comorbidities dictate ANALGESIA

• Opioid analgesics may be needed (especially after remifentanil usage) in the early postoperative period. • Non-opioid analgesics such as COX-2 selective NSAIDs – Provide excellent analgesia without impairing platelet function or altering bleeding times – Extreme discretion is necessary with the use of COX-2 selective drugs in patients at risk of thrombotic complications. • Non-selective NSAIDs should be avoided due to the risk of perioperative bleeding. • Long-acting local anesthetic infiltration of the surgical field has not been found to improve postoperative pain.

COMPLICATIONS

• Surgical failure of procedure • General risks include bleeding, embolism, infection, anesthetic-related side effects, and transfusion. • Damage to adjacent structures: – Brain: CSF leak, meningitis, headaches, hemorrhage – Eye: Blindness, visual changes, double vision, nasolacrimal duct damage, extraorbital muscle injury, intraorbital hemorrhage, watery eyes – Nasal: Hemorrhage, anosmia, adhesions – CV: Carotid artery damage leading to stroke or death

PROGNOSIS

• 80–90% rate of success of surgery – Prognosis is improved in patients with recurrent acute or chronic infective sinusitis, and those presenting with symptoms of facial pain and nasal blockage.

REFERENCES

1. Al-Mujaini A, Wali U, Alkhabori M. Functional endoscopic sinus surgery: Indications and complications in the opthalmic field. OMJ. 2009;24:70–80. 2. Bajaj Y, Gadapelli C, Reddy TN. Functional endoscopic sinus surgery: Review of 266 patients. Internet J Otorhinolaryngol. 2007;6(1).

3. Baker AR, Baker AB. Anaesthesia for endoscopic sinus surgery. Acta Anaesthesiol Scand. 2010;54(7):795–803.

4. Tirelli G, Bigarini S, Russolo M, et al. Total intravenous anesthesia in endoscopic sinus: Nasal surgery. Acta Otorhinolaryngol Ital. 2004;24(3):137–144. (C) 5. Yoo HS, Han JH. Comparison of surgical condition in endoscopic sinus surgery using remifentanil combined with propofol, sevoflurane, or desflurane. Korean J Anesthesiol. 2010;59(6):377–382. (C) See Also (Topic, Algorithm, Electronic Media Element) Controlled hypotension

CLINICAL PEARLS

• Minimally invasive technique with a low risk of major complications (CSF leak most common). • The goal of the procedure is to restore sinus ventilation and normal mucociliary drainage of the sinuses. • TIVA with propofol, remifentanil, and LMA have been shown to provide excellent operating conditions in suitable patients. • Minimizing conditions that may predispose the patient to increased bleeding perioperatively is of great importance.

ENDOVASCULAR ANEURYSM REPAIR (EVAR) Jared Feinman, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION General

• Endovascular aortic repair (EVAR) is a minimally invasive technique that was initially introduced in the early 1990s for patients with poor health status that were considered “unfit" for open aortic repair. • EVAR is now widely used in elective cases and is garnering potential for ruptured abdominal aortic aneurysm (rAAA) repair. • Large vascular sheaths are introduced into the femoral arteries, through which guidewires, catheters, and stent grafts are then passed. • Fluoroscopy is utilized to perform a pre-intervention angiogram (to confirm preoperative CT measurements) and subsequently guide stent deployment. • The stent graft is advanced to the level of the aneurysm, carefully positioned at the top and bottom of the defect, and opened. Opening occurs by removal of the sheath, allowing radial forces of self-expanding stents and active fixation using hooks or barbs that attach to the artery wall to hold the graft firmly in place (against normal aortic intima proximal and distal to the aneurysm). This creates “new walls” in the aorta through which blood flows and “excludes” the aneurysm, which will eventually thrombose around the stent graft. • Anatomic criteria for successful EVAR: – Femoral or external iliac arteries are sheath insertion points, and must be >7 mm in diameter (tortuosity, calcifications, stenotic disease may also complicate sheath insertion). – Proximal aortic neck diameter should be 18–28 mm. Additionally, there should be at least 15 mm of non-aneurysmal artery to allow successful proximal fixation of the stent. Presence of mural calcifications, thrombus, and angulation are secondary considerations. – Common iliac artery is the usual distal attachment site, and should be 8–20 mm in diameter. Additionally, there should be at least 20 mm of non-aneurysmal artery to allow successful stent fixation. • Advantages of EVAR over open repair: – Avoids a large abdominal incision that can be associated with increased bleeding and the need for transfusion, significant postoperative pain with resultant pulmonary dysfunction, inflammation, and third-spacing. There is also less potential for injury to surrounding structures. – Reduced hospital stays and ICU admissions – Avoids aortic cross-clamping and unclamping which can be associated with significant hemodynamic shifts, distal ischemia, and renal injury – Allows for anesthetic choice: Monitored anesthesia care (MAC), general anesthesia (GA),

or neuraxial blocks – Hypothermia is less likely. – Associated with reduced 30-day postoperative morbidity and mortality in elective repair, rAAA repair, elderly patients, and high-risk patients compared to open procedures. • Disadvantages of EVAR over open repair: – Not suitable for 20–50% of AAA repairs – Annual surveillance CT angiograms are required to assess graft positioning and endoleak. – Pre-procedural imaging is required to assess the anatomic criteria; thus, it may not be suitable in a hemodynamically unstable rAAA. – Increased cost for stents and annual CT scans. However, this may be offset by reduced hospital stay and morbidity (i.e., renal injury). – Increased need for re-interventions (endoleaks, device failure, access site hematomas and infection, aneurysmal remodeling) – Long-term survival benefit versus open AAA repair may not be sustained (studies have shown equivalent all-cause mortality at 2- and 5-year follow-up).

Position

• Supine • Prep from nipples to knees in anticipation of immediate conversion to open surgery

Incision

Bilateral, small femoral arteriotomy at the level of the groin Approximate Time 1–3 hours

EBL Expected 250 mL

Hospital Stay

• 2–3 days (vs. 5–10 days for open repair) • 10 days for rAAA

Special Equipment for Surgery

• Stent-equipped balloon catheter • Fluoroscopy, IV contrast dye • Capability to convert to open repair

EPIDEMIOLOGY Prevalence

50,000 AAA repairs are performed annually; approximately 43% are EVAR. Prevalence

Increases with age, male gender, smokers, hypertension, family history, connective tissue disease

Morbidity

• Re-intervention is 20% (compared to 6% with open repair)

Mortality

• 30-day mortality for elective repair (compared to 4.6% for open); however, the trend toward an early mortality advantage may be lost as early as 12 months, with no difference in allcause mortality at 5 years (DREAM trial). • A benefit in overall or aneurysm-related mortality may not exist over medical management in patients unfit for open surgery. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patient population with significant comorbidities • Cardiac complications are the most common, significant perioperative complication, and cause of late mortality • Nephrotoxicity from IV contrast dye; particularly in patients with pre-existing renal dysfunction. Consider renoprotective measures. • Prepare to convert to an open repair “electively” or emergently.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Often asymptomatic • Expansion can present with pain. • Pulsating sensations in abdomen, chest, lower back, or scrotum • Rupture presents with severe, sudden, or persistent pain in the abdomen or back; clammy skin, shock, nausea, vomiting

History

• Often found incidentally on imaging for other complaints • Careful assessment of comorbidities; patients are “vasculopaths,” and disease of the cerebral, myocardial, renal, and peripheral vasculature may also be present.

Signs/Physical Exam

• Palpable abdominal mass • Abdominal bruits may be noted.

MEDICATIONS

• Beta-blockers lower the number of pulsations and strength of contractility against the aneurysmal wall. Outcome studies have shown a reduction in cardiac and overall morbidity and mortality (DECREASE study), but there may be an increase in stroke risk (POISE study). • Anticoagulants (clopidogrel, heparin, aspirin, warfarin)

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, creatinine • PT/PTT, INR • Hemoglobin • Ultrasound of the aneurysm to assess for size and the presence of free peritoneal fluid • CT scan provides 100% sensitivity in detection and also allows for preoperative anatomic planning, including consideration for EVAR.

CONCOMITANT ORGAN DYSFUNCTION • Cerebrovascular disease • Coronary artery disease • Peripheral vascular disease • Chronic obstructive pulmonary disease

TREATMENT PREOPERATIVE PREPARATION Premedications

• Perioperative beta-blockers should be titrated to heart rate and balanced against drops in blood pressure or increased peak inspiratory pressures in reactive airway disease. Introduction to, and initiation of, therapy should also be considered. • Statins should be continued perioperatively. Introduction to, and initiation of, therapy should also be considered. Studies have suggested that patients started on statins prior to major vascular surgery may have reduced hospital length of stay, postoperative complications, overall cost, incidence of renal complications, and mortality. However, guidelines do not exist as to drug selection, dosing, minimal treatment period, or other criteria at this time. Special Concerns for Informed Consent

• Blood consent for potential transfusion (especially if converted to open repair) • Potential for postoperative intubation

INTRAOPERATIVE CARE Choice of Anesthesia

• GA with ETT for pulmonary disease, Parkinson’s, chronic back pain, rAAA • Monitored anesthesia care • Regional (epidural, CSE) T12 level; need to inquire about anticoagulation medications, may need preoperative PT/PTT/INR. Not contraindicated by usual intraoperative heparinization. Follow ASRA guidelines for removal. If insertion is traumatic, the case may need to be delayed. Monitors

• Arterial line (beat-to-beat blood pressure monitoring, ACT, labs): Consider preoperative placement if there is a potential for HD instability during induction. • 2 large-bore IVs (14–18 g) for rapid resuscitation in case of rupture or emergent conversion

to open repair • Central line access not usually necessary unless left ventricular dysfunction or poor IV access • Foley catheter (allows adequate hydration with IV contrast dye)

Induction/Airway Management

Slow, controlled induction; avoid coughing, bucking, HD instability that may cause rupture or exacerbate ischemia or COPD. Maintenance

• Heat loss can result from significant exposure during prepping and draping. • Stent deployment needs to take place during apnea (if GA, hold ventilation; if MAC/regional it requires patient to be able to follow commands). • Low HR reduces movement interference of the image (systolic beats cause aortic wall distension). • Marked hypotension may indicate retroperitoneal or intra-abdominal bleeding. • Heparinization may require repeat dosing and monitoring of ACTs with a goal of 200–250. Reversal with protamine may be required and should be discussed with the surgeon. • Stent deployment can result in brief ischemia distal to the graft. • Diligent assessment of UOP: Consider renoprotective measures against contrast-induced nephrotoxicity, particularly in patients with baseline renal insufficiency. These include sodium bicarbonate, mannitol, adequate IV fluid hydration, and statins.

Extubation/Emergence

• Avoid coughing and bucking • Avoid hypertension. Consider antihypertensive drip such as diltiazem, nitroglycerin, nitroprusside, and/or esmolol. • Postoperative neurologic exam to assess for cerebral and peripheral ischemia

FOLLOW-UP BED ACUITY

• Telemetry or ICU • No flexion at groin for several hours after removal of large arterial sheaths • Antiplatelet therapy (clopidogrel, aspirin), statins, and beta-blockers may need to be started or continued postoperatively.

ANALGESIA

• Pain is typically mild; local anesthetic infiltration, NSAIDs, and PO opioids are often sufficient. • Epidural catheters should be removed using ASRA guidelines, and only after documenting normal coagulation status.

COMPLICATIONS

• Rate of secondary intervention following EVAR is 10–15% per year, most commonly for endoleak.

• Endoleak: Extravasation of blood outside of the stent graft and into the aneurismal sac (seen in 20–30% of all EVARs during early postoperative period) – Type I: Leak at proximal or distal graft attachment site (<5% of all leaks, and 80% heal spontaneously by 6 months) – Type II: Flow to and from the aneurysm sac by patent branch vessels (20–30% of all leaks, about 50% of these heal spontaneously) – Type III: Junctional leak due to overlapping device components – Type IV: Increased porosity of graft fabric, heals spontaneously over time • Endotension: In 5% of EVARs, the aneurysm continues to grow despite the absence of any leak. Etiology of endotension remains unclear, but patients may require eventual open repair. • Stent graft device issues: Fracture of metallic components (stents, hooks, or barbs), tears in the fabric component, inadequate proximal or distal seal zone, thrombus or calcification that limits stent purchase, or migration may require revision. • Acute dissection or rupture (1–1.5% per year after EVAR) requires emergent open repair or EVAR revision. • Embolization of atheromatous or thrombotic debris causing ischemia or stroke • Retroperitoneal hemorrhage • Postoperative delirium in the elderly • Adverse cardiac events (ischemia, infarct, arrhythmias, CHF, hypertension, hypotension) • Renal injury from IV contrast (∼50–80 mL of dye used for intraoperative angiograms) and/or deployment of the stent over the renal arteries • Postoperative fever and leukocytosis are common. • Access site infection or hematoma

REFERENCES

1. Greenhalgh RM, Powell JT. Endovascular repair of abdominal aortic aneurysm. N Engl J Med 2008;358(5):494–501. 2. Eliason JL, Upchurch GR. Endovascular abdominal aortic aneurysm repair. Circulation 2008;117:1738–1744. 3. DREAM Study Group. Long-term outcome of endovascular repair of abdominal aortic aneurysm. N Engl J Med. 2010;362:1881–1889. 4. Bakker EJ, van de Luijtgaarden KM, van Lier F, et al. General anaesthesia is associated with adverse cardiac outcome after endovascular aneurysm repair. Eur J Vasc Endovasc Surg. 2012. 5. Hyhlik-Durr A, Bischoff MS, Hakimi M. Technical aspects of EVAR for infrarenal AAA. J Cardiovasc Surg. 2012;53(1 Suppl 1):111–118.

ADDITIONAL READING • DECREASE study • EUROSTAR study

See Also (Topic, Algorithm, Electronic Media Element)

• Abdominal aortic aneurysm • Abdominal aortic aneurysm (open repair)

CODES ICD9

441.9 Aortic aneurysm of unspecified site without mention of rupture ICD10 I71.9 Aortic aneurysm of unspecified site, without rupture

CLINICAL PEARLS

• Minimally invasive procedure with reduced 30-day morbidity and mortality compared to open repair; however, the survival benefit is lost as early as 12 months. • Beta-blockers and statins should be continued perioperatively; some evidence to suggest that initiation of therapy confers a survival benefit. • Acute dissection or rupture requires emergent conversion to an open repair. • There is some evidence showing that general anesthesia is associated with an increased risk of cardiac events compared to local/regional techniques.

EPIDURAL

Sharon L. Lin, MD Jane C. Ahn, MD

BASICS DESCRIPTION

• A technique for accessing the epidural space in order to deliver medications. Epidurals are placed perioperatively for analgesia, surgical anesthesia, and in laboring patients. Pain physicians also perform the procedure for diagnostic and therapeutic purposes. • Epidurally administered medications are delivered close to their intended site of action, as opposed to the intravenous route. This allows the anaesthetist to deliver smaller doses, with the benefit of reduced side effects. Furthermore, medications within the epidural space serve in an “extended release” capacity. PHYSIOLOGY PRINCIPLES

• Epidural kits: Accessing the epidural space requires the use of a hollow bore needle (varies in length, diameter, and sharp edge). Single shots can be performed with a 19 G Crawford epidural needle; continuous catheters can be placed with a styletted Tuohy epidural needle that is usually 16–18 G and 8–10 cm in length. Syringes are available in glass or plastic. • Identification of the epidural space relies on tactile sensation. Unlike IVs where blood return confirms correct location or intrathecal/spinal blocks where CSF return confirms location, epidural placement relies on a slight change in resistance to injection. – Loss of resistance technique utilizes fluid or air; chronic pain physicians often utilize radiographic imaging to assist with correct placement. No difference in block success has been identified between air and saline for localization of the epidural space. Air may be associated with a patchy block, or rarely pneumocephalus or subcutaneous emphysema. • Indwelling catheters allow for medication delivery either as repeat boluses or continuous infusions. Stiff, plastic catheters facilitate easy insertion; however, paresthesias and intravascular catheter insertion may be more frequent. Flexible wired catheters may result in a slightly more difficult insertion, but may reduce the likelihood of puncturing intravascular or intrathecal spaces. Patient-controlled epidural analgesia (PCEA) allows for continuous infusion with patient-initiated bolus dosing and has been associated with overall lower drug usage and higher patient satisfaction. • Depth of insertion <4 cm may increase the risk of catheter dislodgement by patient movement whereas insertion >6 cm increases the risk of migration into the subdural or intrathecal space or knot development. • Medications commonly used include local anesthetics, opioids, vasopressors (epinephrine, phenylephrine), and clonidine. All medications need to be preservative-free to avoid undesired effects (i.e., transient neurologic symptoms). • Local anesthetics produce differential blockade; nerve fibers have different sensitivities due to their location in the spinal cord, diameter, and the presence or absence of myelin.

Sympathetic nerve fibers are blocked first, and are usually followed by pain, touch, and motor blockade. Large, myelinated nerve fibers are more sensitive to local anesthetic blockade compared to smaller, unmyelinated fibers. – Concentration: Affects block density – Volume: Influences spread and the number of segments blocked (taller patients require larger volumes). – Dermatomal distribution: Approximately 1–2 mL of local anesthetic is required to block each anatomic segment. Generally half of the volume spreads cranially and half spreads caudally; however, spread may be greater cranially. • Opioids: Effective as a sole or adjuvant analgesic agent when administered epidurally. They do not generally cause hypotension. Choice is often based upon availability, institution, and pharmacokinetics (lipid solubility, duration of action, onset, and safety profile). – Lipid solubility: Lipophilic opioids (fentanyl, sufentanil) have effects at the spinal cord and systemically (secondary to vascular absorption). Hydrophilic opioids (morphine) have effects primarily at the spinal cord. – Onset and duration of action: Lipophilic opioids provide rapid onset of analgesia and reduced respiratory depression due to rapid clearance from CSF. Hydrophilic opioids produce a delayed but longer duration of analgesia along with a higher incidence of side effects due to cephalic or supraspinal spread. • Vasoconstrictors: Epinephrine enhances anesthetic depth and duration by decreasing the rate of vascular absorption of local anesthetic. It is also an indicator of inadvertent intravascular injection. Phenylephrine is not as effective as epinephrine. • Bicarbonate increases the pH of the local anesthetic solution and the proportion of drug in its un-ionized form (capable of intraneuronal diffusion to access its site of action); thus it shorten the block onset time. Usual dose is 1 mL per 10 mL of local anesthetic. • Clonidine: Prolongs and intensifies epidural local anesthetic effects via agonism of alpha-2 receptors on primary afferents, interneurons, and descending noradrenergic pathways found in the spinal dorsal horn. Side effects include sedation, dry mouth, and dose-dependent hypotension and bradycardia. • Dexmedetomidine: Analgesic effect via alpha-2 receptor agonism at the spinal cord. Rapid diffusion into CSF with epidural effects seen in 5–20 minutes. • Ketamine: Safety in epidural space is not established. Racemic mixtures are associated with neurotoxicity, but the preservative-free S(+) enantiomer may be safe. • Steroids: The optimal dose, site of injection, and concurrent use of local anesthetics have not been established in randomized controlled trials. Epidural steroid injections appear to benefit patients with radicular pain and disc herniation, but only on a short-term basis. • Dermatomes: Catheter incision-congruent epidural analgesia is associated with superior analgesia, decreased morbidity, and minimal side effects such as lower extremity motor block and urinary retention. • Pressure changes in the pleural cavity are transmitted to the paravertebral space, then to the epidural space. Deep inspiration will increase the negative epidural pressure, while coughing will produce positive pressure.

ANATOMY

• The anterior border of the epidural space is comprised of the posterior aspect of the

vertebral body that is covered by the posterior longitudinal ligament. The posterior border is formed by the ligamentum flavum. • Epidural space communicates freely with paravertebral spaces and root sleeves; it contains blood vessels, anterior and posterior spinal nerve roots, lymphatics, fat, and the filum terminale. Epidural fat is loose and allows injected fluid to diffuse through it. Unilateral blocks can result from segmentation by tissue. • When performing a lumbar epidural, the needle passes through skin, subcutaneous fat, supraspinous ligament, interspinous ligament, and ligamentum flavum. Thoracic epidural placement via paramedian approach bypasses the supraspinous and interspinous ligaments.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Epidural hematomas may be secondary to traumatic neuraxial block, anticoagulants, or spontaneous bleeding from a spinal arteriovenous malformation. Patients present with sudden, severe back pain with a radicular component. Neurologic deficits may progress over hours to days. • Epidural abscess is an infection with inflammatory granular tissue or pus in the epidural space; there is a potential for rapid neurologic impairment due to spinal cord compression. • Nerve damage: Permanent neurologic injury is rare. Techniques to avoid nerve injury include minimal sedation during placement, discontinuing advancement if a paresthesia is encountered, and insertion below the spinal cord when possible (L1 in adults, L3 in infants and children). • Postdural puncture headache is likely from a low-pressure CSF leak that is worsened by standing or straining, but relieved by lying supine. It develops in approximately 50–70% of patients after accidental dural puncture with an epidural needle. The sitting position increases CSF hydrostatic pressure and may increase inadvertent dural puncture. • Medication issues: Local anesthetics can cause hypotension and bradycardia, motor block, nausea and vomiting, toxicity, and urinary retention. Opioids can cause nausea, vomiting, pruritus, constipation, systemic absorption, delayed respiratory depression requiring frequent monitoring or continuous pulse oximetry, and urinary retention with potential delayed discharge. • Total spinal: Inadvertent introduction of local anesthetics into the intracranial subarachnoid space may result from unintentional dural puncture during placement, catheter migration, or subdural spread. • Adhesive arachnoiditis is associated with 2-chloroprocaine. • Epidural catheter breakage can occur intrathecally, intravascularly, or subcutaneously. • Failed epidural or placement of nonfunctioning epidural catheter ranges from 6% to 25%. Unilateral block is more common when catheter insertion is >5 cm into the epidural space or when the epidural needle is aimed towards a unilateral nerve root during insertion.

PERIOPERATIVE RELEVANCE

• Indications: Intraoperative and postoperative pain relief for lower limb, pelvic, lower/upper abdominal, and thoracic surgery as well as nonsurgical pain • Contraindications (absolute): Patient refusal, bleeding diathesis/coagulopathy, infection at the insertion site, and proven local anesthetic allergy • Contraindications (relative): Bacteremia, increased intracranial pressure, hypovolemic

shock, pre-existing neurologic injury or disease, severe valvular cardiac disease, previous back surgery at the site of blockade, and certain thromboprophylaxis regimens • Surgical anesthesia: Epidural anesthesia may also be utilized as a primary anesthetic with or without MAC. With any epidural placement, preparation for airway management and a difficult airway is necessary due to potential complications such as failed epidural, high or total spinal, or local anesthetic systemic toxicity. Blockade to the mid-thoracic level does not significantly change tidal volume, vital capacity, and minute ventilation in patients with adequate lung function. Patients with severe chronic lung disease who are dependent on accessory muscle function may be at higher risk of respiratory distress. – In contrast to spinal analgesia, epidural analgesia requires a longer onset, has a longer duration of action after single bolus injections, and increased medication dose is utilized compared to spinals. Appropriate level of insertion is more important as compared to spinal medications where the level of anesthesia may be adjusted significantly using the effect of gravity. • Postoperative analgesia: Catheters may be placed preoperatively or postoperatively. Preoperative placement can allow for easier positioning and improved pain control on emergence. Benefits of epidural analgesia include decreased postoperative pulmonary complications, lower incidence of deep venous thrombosis, attenuation of stress response to surgery, reduced intraoperative blood loss, reduced mortality, and facilitation of earlier return of GI motility via attenuation of spinal reflex inhibition of the GI tract. • T4–8 catheter insertion: Thoracotomy, video-assisted thoracic surgery (VATS), radical mastectomy, thymectomy, post-traumatic rib fractures. Results in improved ventilation with consequent decreases in postoperative pulmonary complications (hypoxia/atelectasis, infection). • T6–8 catheter insertion: Whipple procedure, gastrectomy, duodenectomy, esophagectomy, hepatic resection • T7–10 catheter insertion: General abdominal surgery, cystoprostatectomy, nephrectomy • T8–11 catheter insertion: Abdominal aneurysm repair, colorectal surgery, radical prostatectomy, total abdominal hysterectomy • L1–L4 catheter insertion: Femoral-popliteal bypass, knee surgery, other lower extremity surgery • Epidural blood patch is effective in 50–70% of patients with postdural puncture headaches. After accessing the epidural space, approximately 20 mL of freshly drawn blood is slowly injected into the epidural space after obtaining the blood using sterile technique. • Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia leads to dilation of normal and stenotic coronary arteries.

Pregnancy Considerations

• Labor epidurals: Benefits include avoidance of hyperventilation, decreased circulating catecholamines, uterine relaxation, and patient comfort. Neuraxial blocks are the preferred anesthetic technique in parturients as it avoids instrumenting a potentially difficult airway and allows the mother to remain awake during their baby’s birth. Early labor epidural placement is advantageous in high-risk patients as it may be used for surgical anesthesia in the event of an emergency Cesarean section. There is a higher incidence of unintended epidural vein cannulation due to epidural venous engorgement.

• Higher incidence of unintended epidural vein cannulation is reported in pregnant patients due to epidural venous engorgement.

Geriatric Considerations

Intervertebral foramina decrease in size with increasing age, resulting in higher block levels for similar epidural doses of local anesthetic. Additionally, a decrease in adipose tissue within the epidural space may also decrease dose requirements. Pediatric Considerations

The distance from the skin to the epidural space is approximately 1 mm/kg between 6 months and 10 years of age. Usual volumes of injectate range from 0.5–1 mL/kg (up to 20 mL).

REFERENCES

1. Ellis H. The anatomy of the epidural space. Anaesth Intens Care Med. 2009;10(11):533– 535. 2. Fischer B. Techniques of epidural block. Anaesth Intens Care Med. 2009;10(11):552–556. 3. Saberski LR, Kondamuri S, Osinubi OY. Identification of the epidural space: Is loss of resistance to air a safe technique? A review of the complications related to the use of air. Reg Anesth. 1997;22(1):3–15. 4. Tiso RL, Thomas PS, Macadaeg K, et al. Epidural catheter direction and local anesthetic dose. Reg Anesth. 1993;18:308–311. 5. Visser WA, Lee RA, Gielen MJ. Factors affecting the distribution of neural blockade by local anesthetics in epidural anesthesia and a comparison of lumbar versus thoracic epidural anesthesia. Anesth Analg. 2008;107(2):708–721. 6. Waurick R, Aken HV. Update in thoracic epidural anaesthesia. Best Pract Res Clinic Aneaesthesiol. 2005;19(2):201–213. See Also (Topic, Algorithm, Electronic Media Element) • Total spinal • Combined spinal epidural • Epidural hematoma • Epidural abscess

CLINICAL PEARLS

• Adjuvant drugs such as opioids added to the local anesthetic solution will improve the sensory blockade, improve pain scores, and allow a lower concentration of local anesthetic to be used. • Case reports of complications associated with the use of air for the loss of resistance technique include pneumocephalus, venous air embolism, subcutaneous emphysema, and spinal cord and nerve root compression. Inadequate anesthesia (“patchy block”) has also been reported with air. The use of saline may reduce the incidence of these complications; however, there is no definite consensus.

• Continuous epidural analgesia may significantly benefit the patient, but only if there is an acute pain service or physicians immediately available to troubleshoot and provide boluses of epidural catheters when needed. • If PCEA is not available, an IV PCA should be ordered to supplement epidural analgesia and provide increased patient satisfaction. • The distance from the skin to the epidural space is 4–6 cm in the majority of the population (~80%). It is generally recommended that the epidural catheter be inserted 5 cm into the epidural space.

EPIDURAL ABSCESS Sharon L. Lin, MD Jane C. Ahn, MD

BASICS DESCRIPTION

• A collection of pus or inflammatory granular tissue in the epidural space with the potential for rapid, irreversible neurologic impairment and death. Requires prompt diagnosis and intervention. • Epidural abscess associated with epidural catheter insertion is fortunately a rare occurrence. However, due to the lack of available information, clear guidelines for diagnosis, treatment, and prevention have not been established in anesthesiology. Extrapolation of infection reduction from other scenarios (surgical site infection) and case reports have been utilized to better understand and describe this complication. • Potential routes of infection include iatrogenic inoculation or contamination, seeding from the bloodstream, or extension from a nearby infected structure. • Among obstetrical patients, infection is the most common cause of neuraxial injury.

EPIDEMIOLOGY Prevalence

• Variable due to low rate of reporting, technical skills of the provider, and other epidemiologic issues • Spinal epidural abscess: 0.2–2 in 10,000 people admitted to hospital • Rare after obstetrical epidural anesthesia

Morbidity/Mortality

• Delayed recognition (presence of neurologic deficit) may lead to permanent neurologic injury, sepsis, and death. • Mortality ranges from 6% to 32%; usually due to sepsis.

ETIOLOGY/RISK FACTORS

• Coexisting risk factors have been shown to be present in up to 80% of reported cases. • Most common risk factors: IV drug use, infection elsewhere in the body, degenerative joint disease, trauma, alcoholism, placement of stimulators or catheters, and neurosurgical procedures • Transient bacteremia and hematogenous spread of infection • Diabetes mellitus • Diagnostic and therapeutic spinal interventions (epidural steroid injections) • Immunocompromised patients • Malignancy • Longer duration of epidural catheterization (possible increased risk after >4 days; however,

studies with mean duration of catheter up to 6 days did not show increased risk) • Age 30 years and older (peak incidence in 60s and 70s) • Morbid obesity • Males • Penetrating injury to the spine or osteomyelitis • Skin infection or abscess • Caudal anesthesia • Poor aseptic technique, performing neuraxial block without surgical mask and hat, or traumatic insertion

PHYSIOLOGY/PATHOPHYSIOLOGY

• Pus or inflammatory granular tissue collections can result in spinal cord dysfunction secondary to inflammation, as well as venous thrombosis, thrombophlebitis, edema, and ischemia secondary to compression of the spinal arteries. • Most epidural abscesses lie posteriorly because the dura mater is adherent to the vertebral column anteriorly. Abscesses can extend easily over several vertebral segments because there are no anatomic barriers in the posterior epidural space. • Potential mechanisms for inoculation include exogenous and endogenous sources: Iatrogenic contamination, the bloodstream, or infection from a nearby source. • Epidural placement by anaesthetists is an opportunity for introduction of skin flora or other contaminants. Staphylococcus aureus is the most common infective organism. Additional bacteria, particularly Staphylococcus epidermidis, reside in large numbers in the deeper recesses of hair follicles and are often difficult to eradicate by antiseptic skin preparations. – Inappropriate sterile technique or a break in sterility – Prolonged catheterization – Traumatic catheter insertion may be associated with breaks in sterile technique and subsequent need for manipulation. – Blood in the epidural space provides a nidus for infection. – Immunocompromised patients (diabetics, chronic steroid therapy, malignancy) – Infection elsewhere: Inflammation at the epidural entry point occurs at a higher frequency when there is an infected wound elsewhere. However, it is not a contraindication to epidural insertion. – Lack of sterile dressing on an indwelling epidural catheter entry point • Labor epidurals: Increased risk in obstetric patients has been associated with catheters being placed outside of the OR (delivery suite), the use of a surgical mask by the anaesthetist, and lack of prophylactic antibiotics. • Bloodstream: Gross or silent bacteremia. In 30–40% of cases, there is no identifiable source and silent bacteremia is believed to be the culprit. • Direct extension: Vertebral osteomyelitis or psoas muscle abscess • Injectate: Racemic bupivacaine is bacteriostatic. • Common bacteria – Gram-positive cocci: S. aureus comprises 50–66% of all cases; of those, 15–40% are caused by MRSA (particularly in patients with implantable spinal or vascular devices); S. epidermis – Gram-negative bacilli: Escherichia coli, Haemophilus influenzae

– Atypical organisms and fungi: Pseudomonas and Mycobacterium tuberculosis are most commonly isolated from IV drug users and patients with tuberculous spondylitis. • Severe and untreated cases can result in coma and cerebral edema.

PREVENTATIVE MEASURES

• Aseptic technique: Wear mask, wash hands in alcohol or full surgical scrub after removing hand jewelry. Prep widely with chlorhexidine in alcohol twice, drape the patient’s back, and use powder-free sterile gloves without touching any unsterile area. • Chlorhexidine is superior to povidone-iodine before epidural catheterization and lowers the incidence of positive bacteriologic cultures. • Use a bacterial filter during continuous epidural infusion. • Limit disconnection and reconnection of neuraxial delivery systems. • Accidentally disconnected catheters should be removed. • Limit the duration of epidural catheterization. • Daily evaluation of indwelling catheters for signs and symptoms of infection (fever, WBC elevation, erythema or tenderness over epidural insertion site). • Monitor neurologic function. • Evidence for prevention of epidural abscess is sparse. Extrapolation from other fields, indirect evidence, logic, and commonsense are utilized; case reports may be the only “evidence.”

PREOPERATIVE ASSESSMENT • Diagnosis may be difficult initially due to nonspecific signs or when neurologic signs or symptoms have not manifested. • Back pain with percussion or palpation of the spine, progressing to paralysis • Erythema, induration or tenderness over epidural insertion site • Neurologic changes can include meningeal signs, headache, paresthesias, difficulty standing, and sphincter incontinence. • Laboratory analysis shows leukocytosis (↑WBC) with a left shift, elevated erythrocyte sedimentation rate, and elevated C-reactive protein. • Blood cultures may be positive. • Perform culture of epidural catheter tip or CSF analysis to determine viral, bacterial, or fungal etiology. • Imaging studies: X-ray may be abnormal if epidural abscess is secondary to spinal osteomyelitis; however, plain x-ray images are neither sensitive nor specific. • CT without contrast is not sufficiently sensitive to soft tissue densities in the spinal canal. • Gadolinium-enhanced MRI is the most sensitive and specific imaging modality. Images demonstrate linear enhancement that surrounds non-enhancing purulent or necrotic matter. • CT myelography may be performed if an MRI is contraindicated; consider sending the CSF for gram stain and culture. • Neurosurgery consultation • Infectious disease specialist consultation

DIFFERENTIAL DIAGNOSIS

• Herniation of intervertebral disc • Vertebral osteomyelitis or discitis • Meningitis • Metastatic tumor • Spinal cord injury • Low back pain • Transient neurologic symptoms • Epidural hemorrhage • Perinephric abscess • Postdural puncture headache

TREATMENT • Some case reports indicate percutaneous drainage of abscess using fluoroscopic guidance or CT-guided aspiration of abscess may be effective. • Surgical intervention: Decompression within the first 24 hours with laminectomy, hemilaminectomy, or interlaminar fenestration is associated with improved prognosis. • Administer antibiotics: Empirical antimicrobial therapy should include a first-line antistaphylococcal agent (vancomycin) plus coverage for aerobic Gram-negative bacilli (cephalosporin or fluoroquinolone). Once cultures return, antibiotic therapy should be tailored. • Prompt removal of in situ catheter if epidural abscess is suspected. • Lumbar puncture is not recommended as it may induce meningitis if the needle traverses the epidural abscess.

FOLLOW-UP • Long-term antimicrobial therapy is often required for 4–6 weeks; 6–8 weeks for patients with contiguous osteomyelitis. • Complete recovery with full neurologic function is likely if neurologic symptoms are present for <24 hours before initiation of therapy. • Final neurologic outcome is assessed at least 1 year after treatment since some patients may continue to regain neurologic function.

CLOSED CLAIMS DATA

• Epidural abscess comprised 4.5% (4/89) of neuraxial anesthesia claims in obstetrical anesthesia (All Claims, n = 368). • Epidural abscess comprised 4% (4/93) of all neuraxial block claims associated with steroid injection (All Claims, n = 93). – Claims resulting in payment: 43% – Payment range: $2,000–$1,812,500

REFERENCES

1. Pradilla G, Ardila GP, Hsu W, et al. Epidural abscesses of the CNS. Lancet Neurol.

2009;8:292–300.

2. American Society of Anesthesiologists. Practice advisory for the prevention, diagnosis and management of infectious complications associated with neuraxial techniques. Anesthesiology. 2010;112:530–545. 3. Borum SE, McLeskey CH, Williamson JB, et al. Epidural abscess after obstetric epidural analgesia. Anesthesiology. 1995;82:1523–1526. 4. Mamourian AC, Dickman CA, Drayer BP, et al. Spinal epidural abscess: Three cases following spinal epidural injection demonstrated with magnetic resonance imaging. Anesthesiology. 1994;78:204–220. 5. Darouiche R. Spinal epidural abscess. N Engl J Med. 2006;355:2012–2020.

ADDITIONAL READING

• Reihsaus E, Waldbaur H, Seeling W. Spinal epidural abscess: A meta-analysis of 915 patients. Neurosurg Rev. 2000;23:175–204. • Sendi P, Bregenzer T, Zimmerli W. Spinal epidural abscess in clinical practice. QJ Med. 2008;101:1–12.

See Also (Topic, Algorithm, Electronic Media Element) • Epidural hematoma • Transient neurologic symptoms

CODES ICD9 324.9 Intracranial and intraspinal abscess of unspecified site ICD10 G06.2 Extradural and subdural abscess, unspecified

CLINICAL PEARLS

• Prevent bacterial contamination by adhering to strict aseptic technique, and wearing sterile gloves, mask, and hat. • Initial clinical presentation of an epidural abscess, however, can be nonspecific. Fever and tenderness over the epidural site may be the only symptoms. • A large meta-analysis divided clinical manifestations into 4 stages (N = 915). However, there appeared to be high inter-individual variability along with time to presentation (hours to days). – Stage 1: Back pain (71%) and fever (66%) – Stage 2: Radicular pain (20%) – Stage 3: Muscle weakness (26%), sphincter incontinence (24%), and sensory deficits (13%) – Stage 4: Paralysis (31%) and quadriplegia (3%) below level of infection

EPIDURAL HEMATOMA (SPINAL) Caroline Fosnot, DO, MS Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Accumulation of blood in the epidural space, resulting in compression or ischemia of the spinal cord. This can have devastating neurologic consequences. • Hematomas remain a potential risk for a number of neuraxial procedures including: – Epidural or spinal anesthesia – Lumbar drain placement – Diagnostic lumbar puncture – Spinal cord stimulator insertion – Epidural or transforaminal steroid injections • It may also occur spontaneously or secondary to surgical trauma.

EPIDEMIOLOGY Prevalence

• Incidence of spontaneous epidural hematomas is unknown. • Epidural hematoma in a patient on fibrinolytic or thrombolytic therapy is estimated at <1%. • Occurrence of an epidural hematoma in association with neuraxial procedures is rare. Given the infrequent occurrence, incidence is estimated: – Epidural ∼1:150,000 – Labor epidurals ∼1:175,000 – Spinal <1:220,000 Morbidity/ Mortality

Spinal cord compression and/or ischemia can result in permanent nerve damage, cauda equina syndrome, and/or paraplegia if left untreated. ETIOLOGY/RISK FACTORS

• Pharmacologic agents: – Anticoagulation agents: Warfarin, heparin, enoxaparin, dalteparin – Fibrinolytic agents: Tissue plasminogen activator, streptokinase, urokinase – Antiplatelet agents: Clopidogrel, ticlopidine • Bleeding disorders: – Hereditary: Von Willebrand disease, hemophilia A, hemophilia B – Acquired: Uremia, preeclampsia, hepatic failure, leukemia, lymphoma, idiopathic thrombocytopenia purpura, hypothermia, disseminated intravascular coagulopathy • Traumatic neuraxial procedure

• Cavernous angioma or arteriovenous malformation (AVM)

PHYSIOLOGY/PATHOPHYSIOLOGY

• Anatomy of the spinal cord: The spinal cord extends to the first lumbar vertebrae (L1) in adults (L3 in children). It is surrounded by 3 meninges (inner to outer): Pia, arachnoid, and dura mater. The CSF accumulates between the pia and arachnoid meninges. • Epidural space: The epidural space is a potential space bound anteriorly by the dura mater and posteriorly by the ligamentum flavum. The epidural space normally contains tissue, fat, and the epidural venous plexus. – Expansion of the epidural space can occur with the introduction of local anesthetics, blood, or pus. • Injury of the epidural venous plexus can result in accumulation of blood within the epidural space. Traumatic neuraxial procedures, particularly in the setting of abnormal coagulation, may lead to compression and/or ischemia of the spinal cord. • Neurologic deficits typically develop within 4–6 hours of the neuraxial procedure; in rare instances, symptoms may develop 4–7 days after a procedure.

PREVENTATIVE MEASURES

• Avoid neuraxial blocks in patients with bleeding diathesis: – Thrombocytopenia – Coagulopathy • Avoid neuraxial procedures in the presence of anticoagulation agents. Guidelines outlined by American Society for Regional Anesthesia (ASRA) (1): – Unfractionated heparin (UFH) SQ: No contraindications if total daily dose <100,000 U; check platelets and PTT if on SQ dose >3 days IV: Discontinue 4 hours; check PTT – Warfarin: Discontinue 4–5 days; INR <1.5 – Low molecular weight heparin (LMWH) (enoxaparin and dalteparin): Prophylactic dosing (enoxaparin 0.5 mg/kg/day; dalteparin 2,500–5,000 U/day): Discontinue 12 hours Treatment dosing (enoxaparin 1 mg/kg b.i.d. or 1.5 mg/kg/day; dalteparin 120 U/kg/day): Discontinue 24 hours Remove catheter 2 hours before LMWH doses – Clopidogrel: Discontinue 7 days prior – Ticlodipine: Discontinue 14 days prior – NSAIDS/Aspirin: No contraindication – Herbal/OTC medications: No contraindications

PREOPERATIVE ASSESSMENT • Severe back pain localized to site of the neuraxial procedure • Radicular pain in appropriate dermatome distribution • Sensory or motor deficits • Depressed reflexes

• Bladder or bowel incontinence • Reduced anal sphincter tone • Coagulation studies: PT, PTT, INR • CBC: Identify infection (WBCs), thrombocytopenia • CT scan: Hyperdense fluid collection impinging on spinal cord • MRI scan: Fluid collection compressing spinal cord • Myelography: Illustrates a space-occupying lesion; not the first choice for an acute workup

DIFFERENTIAL DIAGNOSIS • Epidural abscess • Disk herniation • Local neuritis

TREATMENT • Orthopedic or neurosurgical consult – Decompression within 8–12 hours is associated with improved neurologic outcomes. • Cases with minimal neurologic compromise may be managed conservatively with serial neurologic exams.

FOLLOW-UP • Physical therapy and/or neurologic rehabilitation for deficits • Patient education about risk of epidural hematoma with future neuraxial procedures

CLOSED CLAIMS DATA

• As of 1992, there were 16 cases of spinal cord injury associated with epidural hematomas (2) – Systemic anticoagulation: 13/16 Preoperative heparin: 3/16 Intraoperative heparin: 13/16 Postoperative heparin: 5/16 – Neuraxial procedure: 13/16 Epidural: 11/16 Subarachnoid: 2/16 – Delay in diagnosis: 10/16 Sensory and motor deficits inappropriately attributed to local anesthetic – Payment: 9/16 Median payment: $447,381

REFERENCES

1. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy. Reg Anesth Pain Med. 2010;35(1):64–101.

2. Cheney FW, Domino KB, Caplan RA, et al. Nerve injury associated with anesthesia: A closed claims analysis. Anesthesiology. 1999;90(4):1062–1069.

ADDITIONAL READING

• American Society of Regional Anesthesia Guidelines on Thromboprophylaxis

See Also (Topic, Algorithm, Electronic Media Element) • Epidural abscess • Epidural • Prothrombin time

CODES ICD9 432.0 Nontraumatic extradural hemorrhage ICD10 • S06.4X9A Epidural hemorrhage w LOC of unsp duration, init • S06.4X9D Epidural hemorrhage w LOC of unsp duration, subs • S06.4X9S Epidural hemorrhage w LOC of unsp duration, sequela

CLINICAL PEARLS

• Surgical patients often present with anticoagulation for coexisting embolic disease (cardiac, cerebral, peripheral vascular) and/or perioperative thromboprophylaxis. • Neuraxial procedures and catheter removal should occur in the presence of minimal anticoagulation agents. • ASRA has established guidelines for neuraxial procedures in the presence of anticoagulation agents. • Patients at increased risk of epidural hematoma formation should be monitored closely with serial neurologic exams. • Severe back pain and worsening neurologic symptoms may signify an expanding epidural hematoma. • Prompt diagnosis and treatment improve neurologic outcomes.

EPIDURAL STEROID INJECTION Eric S. Hsu, MD

BASICS DESCRIPTION

• Epidural steroid injection (ESI) is performed to administer long-acting corticosteroids, preservative-free local anesthetics, and normal saline into the epidural space to provide symptomatic pain relief. It has the benefit of: – Delivering medications in close proximity to the inflamed nerve – Minimizing systemic side effects of steroids • Pain relief from ESI is most likely the result of reducing inflammation and is often part of a multimodal approach that also incorporates functional restoration. PHYSIOLOGY PRINCIPLES

• Prostaglandins (particularly prostaglandin E2) and leukotrienes contribute to inflammation, sensitization, and pain at spinal nerve roots (1)[A]. – Phospholipase A2 (PLA2) is the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins and leukotrienes. • Steroids function to decrease inflammation in the epidural space by inhibiting the action of PLA2. Additionally, steroids may also: – Prevent and/or diminish ectopic neural discharge from neuromas – Interfere with nociception by blockade of unmyelinated C-fibers but not A-beta fibers – Reduce capillary permeability • Steroids utilized include: – Methylprednisolone acetate (MPA, Depo-Medrol): 80–120 mg – Triamcinolone acetonide: 80 mg • Dilute local anesthetics may also be administered to offer temporary analgesia without demonstration of any specific level of sensory or motor blockade. – Lidocaine has the advantage of providing a quick onset. – Bupivacaine has the advantage of providing a longer duration. • Normal saline is utilized to dilute the local anesthetic or provide a “flushing” agent that dilutes the chemical or immunologic agents that promote inflammation and pain. • There is no standard volume or composition in ESI. Typical volume of medication solution is 3–9 mL for interlaminar ESI and 10 mL or more for caudal ESI. ANATOMY

• Epidural injections can be performed at the cervical, thoracic, lumbar, or caudal level. • Both interlaminar and transforaminal approaches can be utilized and are based upon the physician’s preference. • Interlaminar ESI (ILESI), also termed translaminar ESI, provides diffuse coverage of the posterior epidural space.

– Epidural needle is utilized. – Technique is similar to perioperative epidural placement with the palpation of landmarks, a midline (or paramedian) approach that begins at the skin, and then through subcutaneous tissue, paraspinal muscles, supraspinous ligament, interspinous ligament, and finally loss of resistance at the ligamentum flavum. – Radiography is utilized in the anteroposterior and lateral positions to aid in advancement and confirmation of epidural spread of contrast. • Transforaminal ESI (TFESI) distributes injectate around the nerve root sleeve as well as into the epidural space. – It may be more precise and effective when the pathogenesis is from a specific nerve root. – The goal is to identify and inject medications at the level of the intervertebral foramen that lodges the specific affected spinal nerve root. – A spinal needle is advanced to the inferolateral margin of the pars interarticularis utilizing C-arm fluoroscopy; oblique view. – The lateral view is then used to guide the needle toward the anterior and superior aspect of the foramen to avoid the exiting nerve root. – If a paresthesia is noticed by the patient during needle placement, the needle should be withdrawn slightly, and the position confirmed with radiographic contrast in both anteroposterior and lateral views. • Caudal ESI (CESI) is an ILESI approach that uses the landmarks of the sacral hiatus and enters through sacrococcygeal ligaments into the sacral canal and epidural space. • Fluoroscopic guidance is utilized to facilitate location and optimal positioning. A test dose of contrast medium confirms the flow along the target nerve and rules out intrathecal and intravascular injections. – 17% of cases of ILESI without radiography can be subdural or superficial to ligament flavum. – 35% of CESI without radiography result in intravascular injection (despite negative heme on aspiration) or failure to reach the epidural space. – Injectate of ESI may not reach the target level or interface even with correct needle placement in the epidural space. – It is possible to thread a catheter from the caudal space to higher lumbar levels to ensure that medications reach appropriate levels.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Radicular pain is a sharp, lancinating, radiating pain, often shooting from the low back down to the lower limbs in a dermatomal distribution. It is the result of mechanical and inflammatory irritation. – Inflammation and nerve root edema have been demonstrated on radiographic imaging, surgical findings, and histologic examination. – Clinical manifestations of nerve root inflammation include some or all of the following: Radicular pain, dermatomal hypesthesia, weakness of muscle groups innervated by the involved nerve root(s), diminished deep tendon reflexes, and positive straight or reverse leg-raising tests. – Mechanical compression alone usually causes only motor deficits and altered sensation but does not necessarily cause pain.

– Chronic inflammation can result in edema, Wallerian degeneration, and fibrotic changes to the neural tissues. • Animal models have demonstrated inflammatory mediators in herniated disc material, such as PLA2, interleukins, tumor necrosis factor-α, and nitric oxide. Animal models demonstrated: – Motor weakness, demyelination of nerve roots, and decreased withdrawal thresholds with administration of PLA2 in lumbar nerve roots. – Thermal hyperalgesia and motor weakness with ligation of spinal nerve roots. – A reduction of thermal hyperalgesia lasting 3–4 weeks following ESI. • Complications of ESI include medication effects and needle trauma. – Corticosteroids are capable of suppressing the hypothalamic–pituitary–adrenal (HPA) axis and plasma cortisol level for up to 3 weeks after a single epidural injection of 80 mg methylprednisolone. Diabetic patients can also see a transient increase in glucose levels. Additionally, epidural steroids have been associated with the development of osteoporosis and arachnoiditis (intrathecal injection). Certain steroid formulations contain benzyl alcohol which is potentially toxic to neural tissue (arachnoiditis, meningitis). – Local anesthetics: Hypotension from sympathetic efferent blockade has been reported in up to 2.5% of lumbar ESIs. Allergic reactions are rare. – Contrast dye reactions often occur within a few minutes after injection. Those with a history may be considered for pretreatment with antihistamines, corticosteroids. – Neurologic injuries from cord compression (hematoma or abscess), direct injection into the spinal cord – Bleeding from vascular injury by the needle – Vasospasm of the artery of Adamkiewicz has been seen with TFESI. – Dural injuries: Puncture may be linked to headaches. – Infectious complications: Epidural abscesses and meningitis – Radiation: Stochastic effects of fluoroscopy

PERIOPERATIVE RELEVANCE

• Studies that convincingly define specific indications for ESI are lacking (2)[B]. • Potential indications for ESI may include: – Herniated disc: The gel-like material (nucleus pulposus) within the disc can bulge or rupture through a weak area in the surrounding wall (annulus). Irritation, pain, and swelling occur when this material extrudes and comes into contact with a spinal nerve. – Degenerative disc: A breakdown or aging of the intervertebral disc can cause collapse of the disc space, tears in the annulus, and growth of bone spurs. – Sciatica: Pain that travels along the sciatic nerve in the buttocks and down the legs. It is usually caused by compression of the 5th lumbar or 1st sacral spinal nerve. – Spinal stenosis: A narrowing of the spinal canal and nerve root canal that can cause back and leg pain, especially when walking. This is typically the result of impaired vascular flow to the nerve root with resultant irritation, edema, and dysfunction. – Spondylolysis: A weakness or fracture of the par interarticularis between the upper and lower facets of a vertebra (spondylolisthesis) can compress nerve roots and cause pain. – Compression fractures with radicular pain – Degenerative scoliosis

– Facet or nerve root cyst with radicular pain – Postherpetic neuralgia – Diabetic neuropathy • Efficacy and outcomes: – There is fair evidence that ESI is moderately effective for short-term (but not long-term) symptom relief of sciatica or prolapsed lumbar disc with radiculopathy (3)[C]. – Most studies have reported that optimal outcome results from a series of 1–3 ESIs by interlaminar, caudal, or transforaminal approach. – Symptoms <3 months have a positive response rate of 90%; <6 months it reduces to 70%; >1 year further reduction to 50%. – Studies suggest that no more than 3 ESIs should be performed in the absence of clinical benefit. • Contraindications: – Local and systemic infections – Pregnancy – Bleeding disorders – Poorly controlled comorbidities such as diabetes, congestive heart failure, renal disease – Acute spinal cord compression – Allergic reactions to contrast, corticosteroid, local anesthetic • Procedure: – Performed in a sterile procedure room – Intravenous access for cervical spine procedures is usually attained prior to the procedure; not routinely placed for lumbar procedures. – Mild or no sedation may be administered; patient should be able to communicate with the physician. – Positioning is often prone, but can also be performed in the sitting or lateral position. – Appropriate postoperative recovery room monitoring to assess for hemodynamic change and sedation • Pain relief is seen in several stages: – Immediate pain relief is from the local anesthetic. – Maximal relief may take up to 7 days after ESI. – Benefit from ESI may last weeks to months depending on original pathology and therapy (4)[C].

REFERENCES

1. DePalma MJ, Slipman CW. Evidence-informed management of chronic low back pain with epidural steroid injections. Spine J. 2008;8(1):45–55. 2. Friedrich JM, Harrast MA. Lumbar epidural steroid injections: Indications, contraindications, risks, and benefits. Curr Sports Med Rep. 2010;9(1):43–49. 3. Chou R, Atlas SJ, Stanos SP, et al. Nonsurgical interventional therapies for low back pain: A review of the evidence for an American Pain Society clinical practice guideline. Spine. 2009;34(10):1078–1093. 4. Armon C, Argoff CE, Samuels J, et al. Assessment: Use of epidural steroid injections to treat

radicular lumbosacral pain. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2007;68(10):723–729.

ADDITIONAL READING

• Dagenais S, Tricco AC, Haldeman S. Synthesis of recommendations for the assessment and management of low back pain from recent clinical practice guidelines. Spine J. 2010;10(6):514–529. • Manchikanti L, Boswell MV, Singh V, et al. Comprehensive evidence-based guidelines for interventional techniques in the management of chronic spinal pain. Pain Physician. 2009;12(4):699–802. • Rathmell JP. A 50-year-old man with chronic low back pain. JAMA. 2008;299(17):2066– 2077.

See Also (Topic, Algorithm, Electronic Media Element) • Epidurals • Radiation safety

CLINICAL PEARLS

• ESI is indicated for reducing the inflammatory response and radicular pain over the extremity that is associated with acute disc herniation, degenerative disc disease, spinal stenosis, spondylolysis, compression fractures, and postherpetic neuralgia. • ESI has been shown to be moderately effective for short-term (but not long-term) symptom relief of sciatica or prolapsed lumbar disc with radiculopathy. • ESI is commonly incorporated as part of the comprehensive approach in the management of degenerative disc disease and spinal stenosis. It is recommended in a series of up to 3 treatments so clinical efficacy may outlast the half-lives and presumed duration of either local anesthetics or steroids. • Both fluoroscopic guidance and test dose of local anesthetic are crucial in transforaminal ESI.

EPIGLOTTITIS

Brian Gierl, MD Andrew Herlich, DMD, MD, FAAP

BASICS DESCRIPTION

Epiglottitis describes cellulitis of the epiglottis and aryepiglottic folds that may result in extrathoracic airway compromise and require emergent intubation. The condition is more appropriately termed supraglottitis. EPIDEMIOLOGY Prevalence

• Pediatric: 0.7 per 100,000 persons annually in the US (1,2) – Most common age is 3–7 years, although case reports of epiglottitis in infants exist. – Rate reflects 10-fold decrease since Haemophilus influenzae type B (HiB) vaccine was introduced in 1988. • Adult: 1–2 per 100,000 persons annually – Incidence unchanged across several decades Morbidity

No long-term sequelae (1)

Mortality

• Pediatric: Rare • Adult: 0.9% of all cases; mostly secondary to airway compromise and cardiorespiratory collapse, often after discharge with a diagnosis of laryngitis ETIOLOGY/RISK FACTORS

• Etiology – Haemophilus influenza type B; remains the classic etiology in children although up to 10% of children presenting with epiglottitis have a history of HiB vaccination (3). – Group A β-hemolytic streptococci – Staphylococci – Pneumococci – Candida albicans viruses in children and adults • Risk factors – Male:Female ratio of 3:2 – Pediatric: Risk increased without HiB vaccine – Adult: Risk increased with tobacco abuse – Uncommon in the immunocompromised patient • General prevention (3,4)

– Pediatric HiB vaccination

PHYSIOLOGY/PATHOPHYSIOLOGY

• Cellulitis of the epiglottis and aryepiglottic folds with possible epiglottic abscess results in edema and airway obstruction that may lead to cardiorespiratory arrest. – The swollen epiglottis acts as an extrathoracic obstruction, limiting airway inflow velocity (similar to obstructive sleep apnea or vocal cord dysfunction). Expiratory flow (both peak expiratory flow [PEF] and maximum expiratory flow [MEF] rates) and lung volumes are not affected. – Tachypnea further increases inflow velocity and worsens the degree of obstruction, limiting tidal volumes and worsening shortness of breath. • Associated conditions – Concomitant infections, such as otitis media, cervical adenitis, pneumonia, and meningitis, occur in 50% of pediatric patients.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Once the diagnosis is suspected, the patient must be accompanied by a physician capable of providing an emergency airway and should remain seated (the supine position worsens this extrathoracic variable airway obstruction). • Intubate in the OR with personnel and instruments available to obtain a surgical airway. – Rigid bronchoscope – Tracheotomy kit – Cricothyrotomy kit • Pediatric: Adrenergic outflow in the form of agitation or crying can cause tracheal collapse and can lead to clinical deterioration with an already compromised airway. – Avoid racemic epinephrine (the chosen therapy for laryngotracheobronchitis [croup]). Significant airway deterioration has been attributed to further agitation from administration (5).

PREOPERATIVE ASSESSMENT SYMPTOMS

• Fever, odynophagia, dysphagia, muffled “hot potato” voice, stridor – Shortness of breath, tachypnea, tachycardia, and rapid progression are associated with a more serious clinical course and warrant aggressive treatment. – Laryngotracheobronchitis presents with fever, hoarseness, and stridor, without odynophagia or dysphagia.

History

Abrupt onset with symptoms developing over 6–24 hours. This is in contrast to laryngotracheobronchitis, in which symptoms develop over days, typically after an upper respiratory infection. Signs/Physical Exam

• Definitive diagnosis is the direct visualization of a red, swollen epiglottis either under

flexible or direct laryngoscopy. • Patients assume the tripod position, leaning forward with arms on their knees and neck extended to maximize airway diameter. • Stridor, respiratory distress, and drooling are late signs. Inspiratory stridor indicates significant airway narrowing. Progression to biphasic stridor is an even more ominous sign of impending airway collapse. • Delayed capillary filling is common due to dehydration secondary to odynophagia and drooling. • Adults frequently have tenderness to palpation over the hyoid bone.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Lateral neck radiograph obtained with hyperextension during inspiration will reveal a round, thickened epiglottis (“thumb sign”), loss of vallecula air space, and thickening of the aryepiglottic folds. • Direct fiberoptic visualization of an inflamed epiglottis and aryepiglottic folds confirms the diagnosis. • Leukocytosis with left shift and neutrophil predominance is common and indicates a bacterial etiology. • Obtain blood cultures after securing the airway and before initiating broad-spectrum antibiotic therapy (allows the antibiotic regiment to be tailored to the offending organism). • Differential diagnosis: – Pediatric: Laryngotracheobronchitis Bacterial tracheitis Diphtheria Pertussis Tonsillitis Retropharyngeal abscess Foreign body obstruction Allergic reaction – Adult: Laryngotracheobronchitis Mononucleosis Diphtheria Pertussis Tonsillitis Laryngeal mass Allergic reaction

TREATMENT PREOPERATIVE PREPARATION

Premedications

• Avoid depression of respiratory drive in any person with airway compromise. • Pediatric: – Maintain parental contact and avoid anxiety-provoking procedures such as phlebotomy. – Heliox may be used in a cooperative, older child to reduce inspired gas density, increase carbon dioxide diffusivity by 3.5 times, and increase flow rate by 1.8 times through the narrowed airway.

INTRAOPERATIVE CARE Choice of Anesthesia

Pediatric patients without IV access should have an inhalation induction followed by placement of IV access and intubation. Monitors

Standard ASA monitors

Induction/Airway Management

• Pediatric: – Pre-oxygenate and induce anesthesia via an inhalation induction in the upright position while minimizing crying and airway compromise (if IV access exists prior to induction, irrespective of the route of induction, spontaneous ventilation should be preserved at all times, if possible. The use of lidocaine IV 1 mg/kg may be administered to decrease laryngospasm). – A decreased minute ventilation from airway obstruction will slow inhalation induction. – Establish IV access after an adequate depth of anesthesia is achieved and initiate volume resuscitation. – Avoid any neuromuscular blockade prior to securing the airway. – Consider placing a laryngoscope blade into the vallecula to lift the base of the swollen epiglottis and relieve the obstruction. If the glottis aperture is difficult to visualize, consider compressing the chest to expel a glottic bubble. – Place a styletted endotracheal tube under direct vision; choose an ETT 0.5 mm smaller than would otherwise be chosen for the patient. – Have a physician who is competent in the performance of a surgical airway present until the airway is secured. • Adult (2): – Airway intervention is not frequently required. – Consider heliox administration. – Pre-oxygenate and perform awake fiberoptic intubation if required.

Maintenance

Prevent accidental extubation by appropriately securing the endotracheal tube. Extubation/Emergence

• Extubate only after pharyngeal pyrexia has resolved, typically within 24–48 hours.

– Evaluate for the presence of an air leak around the endotracheal tube. – Consider examination of supraglottic structures via fiberoptic bronchoscopy. – Consider extubation in the operating room. • Prevent self-extubation with appropriate sedation and restraints.

FOLLOW-UP BED ACUITY

Intensive care for intubated patient or any patient with diagnosed epiglottitis until their condition improves MEDICATIONS/LAB STUDIES/ CONSULTS

• Broad-spectrum antibiotics effective against β-lactamase producing Haemophilus influenzae with good CSF penetration until blood culture results are available. Ceftriaxone and ampicillin–sulbactam are common choices. • The use of corticosteroids has not been shown to reduce length of ICU stay or hospital stay (5).

COMPLICATIONS

• Pneumonia • Otitis media • Meningitis • Pulmonary edema

REFERENCES

1. Shah RK, Stocks C. Epiglottitis in the United States: National trends, variances, prognosis, and management. Laryngoscope. 2010;120:1256–1262. 2. Frantz TD, Rasgon BM, Quesenberry CP. Acute epiglottitis in adults. JAMA. 1994;272:1358–1360. 3. Shah RK, Roberson DW, Jones DT. Epiglottitis in the Haemophilus influenzae type B vaccine era: Changing trends. Laryngoscope. 2004;114(3):557–560.

4. Guardani E, Bliss M, Harley E. Supraglottitis in the era following widespread immunization against Haemophilus Influenzae type B: Evolving principles in diagnosis and management. Laryngoscope. 2010;120:2183–2188. 5. Kissoon N, Mitchell I. Adverse effects of racemic epinephrine in epiglottitis. Pediatr Emerg Care. 1985;1(3):143–144. 6. Madhotra D, Fenton JE, Makura ZCG, et al. Airway intervention in adult supraglottitis. Ir J Med Sci. 2004;173(4):197–199. See Also (Topic, Algorithm, Electronic Media Element)

• Difficult airway • Tracheostomy • Cricothyrotomy

• Flow volume loops • Laminar flow

CODES ICD9

• 464.30 Acute epiglottitis without mention of obstruction • 464.31 Acute epiglottitis with obstruction • 476.0 Chronic laryngitis ICD10 • J05.10 Acute epiglottitis without obstruction • J05.11 Acute epiglottitis with obstruction • J37.0 Chronic laryngitis

CLINICAL PEARLS

• Pediatrics: – Children are more likely than adults to require intubation due to a smaller baseline airway diameter. – Consider heliox via facemask to improve airflow in a cooperative patient. – Perform an inhalation induction in the child’s desired position while minimizing agitation and maintaining spontaneous ventilation (even if an IV is present). • Adults: – Intubate adult patients with a rapid progression of moderate respiratory distress, stridor, suprasternal retractions, a respiratory rate >30/min, perioral cyanosis, or an arterial carbon dioxide >45 mm Hg over the prior 24 hours (4,6). – Consider helium–oxygen inhalation therapy. – Perform an awake fiberoptic intubation in adults with an endotracheal tube that is 0.5 mm smaller.

ESOPHAGEAL INTUBATION Michael Carter, MD, PHD Laura F. Cavallone, MD

BASICS DESCRIPTION

• Esophageal intubation may occur during attempted tracheal intubation due to the anatomical proximity of the two structures. Possible consequences of inadvertent tube placement or dislodgement into the esophagus during repositioning include: – Injury to the esophagus – Gastric insufflation and aspiration – Hypoxia – Cardiovascular collapse • Intended “esophageal intubations” with orogastric tubes, nasogastric tubes, and esophageal temperature probes can also cause esophageal injury and contribute to injury claims in anesthesiology. EPIDEMIOLOGY Prevalence

• In non-operative emergency settings, esophageal intubation has been reported at rates from 1.3% to more than 5%, varying by study location. • Actual incidence may be higher as many esophageal intubations are recognized immediately and corrected without report. Morbidity/Mortality

• Data from the American Society of Anesthesiologists (ASA) Closed Claims Project Database indicated esophageal intubation as the cause of 13% of claims originating from a respiratory damaging event and resulting in death or permanent brain damage. • Previous analysis reported esophageal perforation as the result in 90% of all esophageal injury claims. • Esophageal perforation may result in infection, pneumomediastinum, pleuritis, or abscess formation. Symptoms may progress to shock or death if untreated. Treatment is usually surgical. If treated within 24 hours, complete recovery is expected. If treatment is delayed, mortality up to 50% can be expected. ETIOLOGY/RISK FACTORS

• Setting: – First responders to trauma scene outside hospital – Emergency rooms – Hospital setting outside the OR (floor codes/emergency airway) • Difficult airway

• Head repositioning • Transport • Age >60 years • Female gender • Anatomical anomalies (tracheoesophageal fistula, laryngeal mass)

PHYSIOLOGY/PATHOPHYSIOLOGY

• Esophageal damage: The normal trachea with its cartilaginous rings is held open for the passage of endotracheal tubes (ETT). The esophagus collapses on itself, and passage of the ETT (even without a stylette) can tear mucosa causing a perforation. • Risk of aspiration increases. Attempts at ventilating after esophageal intubation will insufflate the stomach. The increase in intragastric pressures significantly increases the possibility of aspiration into the pulmonary tree. • Hypoxemia resulting from ineffective oxygenation causes vasodilation, with increases in heart rate and cardiac output as compensatory mechanisms to maximize perfusion. • Cardiovascular collapse can result. Maximal vasodilation will cause hypotension with resultant reductions in perfusion, precipitating shock, and cardiovascular collapse.

PREVENTATIVE MEASURES

• Patient positioning: Obtain optimal sniffing position or other appropriate positioning as indicated by body habitus and comorbidities. • Appropriate monitors: Ensure that the pulse oximetry is on the patient prior to intubation. Always have CO2 detection device available. • Visualization of glottis at intubation: Try to visualize the ET tube passing through the vocal cords. • Have a video or optical intubating device available if a challenging airway is suspected. • Follow the ASA Difficult Airway Algorithm in cases where a difficult airway is encountered, rather than force a blind intubation.

PREOPERATIVE ASSESSMENT • Lung auscultation lacks recognizable breath sounds bilaterally and in all fields. • Stomach auscultation can reveal gurgling sounds while bag ventilation is attempted. • Fiberoptic bronchoscopy remains the definitive gold standard to confirm tube placement. Insertion through the ETT should demonstrate visible tracheal rings and muscular bands. • Real-time ultrasound: The transverse view at the level of the thyroid may be used to detect intubation of the esophagus. The limiting factor may be the experience of the sonograph operator as this technique is not widely used yet. • Esophageal detection devices (EDD) are attached to the ETT after intubation and apply vacuum to the tube. Resistance indicates a collapsed lumen around the ETT, suggesting esophageal intubation. • CXR: Because the proximal airway overlies the esophagus, esophageal intubation may not be distinguished from tracheal intubation. In addition to not necessarily being conclusive, results are also slow to obtain. Thus, it is not recommended as a first choice to confirm tracheal intubation. It is, however, useful for determining endotracheal position of the ETT

(distance from the carina) after confirmed tracheal intubation by other means. • Chest and/or abdominal pain may be seen postoperatively secondary to injury from esophageal intubation from ETT, orogastric tubes, nasogastric tubes, and temperature probes.

MONITORS

• End-tidal CO2 tracing: May show no tracing or a reduced tracing that diminishes over time.

Bag-mask ventilation prior to intubation may result in stomach insufflation with a gas mixture containing exhaled CO2. Also may be confounding in the setting of dead space

ventilation (cardiac arrest, pulmonary embolism). • Pulse oximetry: After esophageal intubation normal oximetric values may be displayed if pre-intubation oxygenation was sufficient. However, without pulmonary ventilation, residual oxygen is taken up by pulmonary capillary blood flow and over time will be exhausted. As the PaO2 begins to fall, the saturation, and thus the pulse oximeter, will begin

to decrease. The time to decrease depends on the residual capacity of the patient and effectiveness of pre-oxygenation. Pulse oximetry may also be less reliable in states of low cardiac output or cardiac arrest. • Colorimetric end-tidal CO2 detectors are devices commonly used in settings outside of the OR (e.g., emergency response teams, floor codes/emergency airways, etc.). They allow for inline rapid detection of CO2 while ventilating the patient. They can give false-negatives in

the setting of cardiac collapse (code situation with reduced cardiac output) or false-positives (gastric insufflation with mask ventilation).

DIFFERENTIAL DIAGNOSIS

It is critical to immediately recognize ETT misplacement in the esophagus. Esophageal intubation often needs to be distinguished from other ETT malpositioning or the inability to ventilate the lungs after intubation. The differential diagnosis includes: • Pharyngeal intubation with the tip of the ETT at level of arytenoid cartilages or above • Selective endobronchial intubation • Herniation of the ETT cuff occluding the tip of the tube and preventing ventilation • Severe bronchospasm causing inability to ventilate and decreased CO2 return • Low cardiac output states and pulmonary embolism (conditions that may present with very low ETCO2 readings)

TREATMENT • Prompt diagnosis of the situation is critical. • Suctioning through the ETT while it is still in the esophagus has been suggested. • Removal of the ETT and replacement in the appropriate position must be performed promptly. A change in airway management technique and/or provider is possibly indicated at this time. • Supportive measures for ventilation (bag-mask ventilation) and perfusion (pressors if

needed) must be provided prior to reintubation as needed. Consider administration of additional anesthetic agents, as appropriate. • Esophageal perforation requires surgical consultation and possible repair.

FOLLOW-UP • Any repositioning or airway manipulation after tracheal intubation requires re-examination and assessment of vital signs and monitors to ensure ETT is still in the trachea and not displaced into the esophagus. • After recognized intubation of the esophagus, patient must be monitored for chest or abdominal pain as those are the first presenting symptoms of esophageal perforation. Fever, tachycardia, dyspnea, and tachypnea are symptoms of progression after esophageal perforation. Surgical consult should be obtained immediately if injury is suspected.

CLOSED CLAIMS DATA

• As mentioned above, an analysis of data from the ASA Closed Claims Project (years 1986– 2000) reported esophageal intubation to be responsible for 13% of events associated with death or permanent brain damage. • Analysis of previous claims (1961–1996) showed esophageal injuries to account for 18% of airway injuries during anesthesia, with the highest mortality (19%) and the largest monetary settlement (median payment $138,975) when compared to all other airway injuries of the same claims period.

REFERENCES

1. Cheny FW, Posner KL, Lee LA, et al. Trends in anesthesia-related death and brain damage. Anesthesiology. 2006;105:1081–1086. 2. Domino KB, Posner KL, Caplan RA, et al. Airway injury during anesthesia. Anesthesiology. 1999;91:1703–1711.

3. Martin LD, Mhyre JM, Shanks AM, et al. 3,423 Emergency tracheal intubations at a university hospital: Airway outcomes and complications. Anesthesiology. 2011;114:42–48. See Also (Topic, Algorithm, Electronic Media Element)

• Laryngoscopy positioning • End-tidal carbon dioxide

CLINICAL PEARLS

• Confirmation of ETT placement should include physical exam as well as monitors; reliance on only one method may delay diagnosis. • Maintain a high index of suspicion if the airway was difficult with a poor view. Consider visual confirmation (fiberoptic bronchoscope, video-assisted laryngoscopy) as quickly as possible if you are unsure or the patient shows clinical signs of inappropriate ventilation and oxygenation. DON’T wait for oxygen desaturation to verify. • Notify the surgical team of any suspected complications and watch for possible esophageal

perforation. • Be aware of other situations that may involve “esophageal intubations” in the perioperative period and their associated risks. Positioning of the following devices may result in injury or perforation, particularly in patients with esophageal hernias or diverticulitis: – Esophageal temperature probe – Orogastric or nasogastric tubes – Transesophageal Doppler and transesophageal echocardiographic probes • Although a rare occurrence, esophageal intubation while accessing the trachea for intubation through a tracheostomy opening or a stoma has been described. It is a possibility to consider in the case of an undiagnosed tracheoesophageal fistula through which the ETT, even though correctly inserted through the tracheal opening, may proceed into the esophagus.

EXTRACELLULAR FLUID

Venugopal S. Reddy, MD, EDIC, FFARCS

BASICS DESCRIPTION

• In an average adult male, 60% of the body weight is water, and in an average adult female, 50% is water. Water is spread across 2 compartments and is in dynamic equilibrium with one another: – Intracellular compartment (ICC): 40% of total body weight, 66% of total body water (∼28 L in a 80 kg male). It is mainly comprised of potassium, proteins, and organic anions. – Extracellular compartment: 20% of body weight, 33% of total body water (∼14 L in a 80 kg male). It is mainly comprised of sodium, chloride, and bicarbonate. This compartment is further subdivided into: Interstitial fluid (fluid lying between the cells or tissue fluid): 15% of total body weight, 24% of total body water (∼10 L in a 80 kg male) Intravascular fluid (plasma): 5% of total body weight, 10% of total body water (∼4 L in a 80 kg male) Transcellular fluid (fluids lying outside the normal components such as CSF, mucus, digestive juices): 2% of total body weight, 2–4% of total body water (∼1–2 L in a 80 kg male). • Movement of proteins, ions, and water between compartments. Although the composition differs between the compartments, all of the body’s fluid compartments are in osmotic equilibrium, except during transient changes. – Intracellular←→Extracellular compartments: The cell membrane consists of a bilipid layer membrane that is laden with protein receptors and ion transport channels that regulate the movement of proteins and ions. Water can move freely. – Interstitial←→Intravascular compartments: These 2 compartments within the extracellular compartment are separated by a capillary endothelium that allows free passage of ions (diffusion based) and water but not large protein molecules (red blood cells, platelets, albumin, etc.). PHYSIOLOGY PRINCIPLES

• Extracellular fluid (ECF) volume is proportional to the total sodium content. It is comprised of an: – Intravascular fluid (IVF) compartment: This is the circulating volume. Approximately 35– 40% of plasma volume is comprised of red blood cells (hematocrit); another 7% is comprised of proteins and lipids. – Interstitial fluid (ISF) compartment: The space between the capillary and the cell; represents the milieu in which the cells are bathed. The ISF is separated from the IVF compartment by the capillary endothelium which allows free passage of ions, but not large protein molecules. Because the ISF is in dynamic equilibrium with the ICC, it has a

different composition in different tissues and in different areas of the body. • Extracellular versus intracellular fluid composition – ECF mainly contains large amounts of sodium cation, chloride anion, and bicarbonate. In addition, it also carries cell nutrients such as glucose, fatty acids, and amino acids. These do not pass freely into the cells, but are carefully regulated based upon metabolic needs and are often hormonally mediated (insulin, growth hormone, etc.). – Intracellular fluid mainly contains potassium cation, followed by magnesium and phosphate anion. The ionic concentrations are carefully regulated by ion channels and ATP-dependent pumps. • Intravascular versus interstitial fluid: The ionic composition is fairly similar; differences exist mainly in the chloride and protein concentration. • Homeostatic control of the extracellular compartment: There are several mechanisms that detect deviations in total body water and osmolarity and maintain them within a narrow range. Maintenance of total body water and osmolarity is carried out mainly by the kidneys. • Osmotic receptors: – Antidiuretic hormone (ADH): Also known as arginine vasopressin. Synthesized in the supraoptic and paraventricular nuclei in the hypothalamus. ADH is the main determinant of renal excretion of water. – Renin–angiotensin–aldosterone: Juxtaglomerular cells in the glomerulus secrete renin. Renin is responsible for the conversion of angiotensinogen to angiotensin I, and this in turn is converted into angiotensin II. – Atrial natriuretic peptide: Secreted by the cells in the cardiac atria in response to distension of atria; opposes the effect of aldosterone and causes diuresis. – Kidneys respond to the above-mentioned hormones to maintain homeostasis. Intrinsically, they also maintain sodium balance, which ultimately determines the ECF volume. • Starling’s law of capillary filtration represents the net fluid filtration at any point within a systemic or pulmonary capillary. Q = Ka [(Pc – Pt) – s (Πc – Πt)], where: – Q = Net flow of fluid; values >0 indicate flow out of the capillary and values <0 indicate flow into the capillary – Ka = Capillary permeability – Pc = Capillary hydrostatic pressure; dominant force at the arterial end of a capillary – Pt = Interstitial hydrostatic pressure

– s = Staverman reflection coefficient for albumin, pulmonary lymph flow, interstitial space geometry, and compliance – Πc = Colloid oncotic pressure; dominant force at the venous end of the capillary

– Πt = Tissue oncotic pressure

• Increased capillary hydrostatic pressure (Pc), decreased colloid oncotic pressure (Πc), and

increased tissue oncotic pressure (Πt) would increase filtration of fluid from the

intravascular bed to the interstitial space causing interstitial edema. Increased interstitial hydrostatic pressure (Pf) and a decreased tissue oncotic pressure (Πt) would decrease filtration. It is also important to appreciate that an increased capillary permeability and a decrease in pulmonary lymphatic flow tend to encourage edema formation.

• Variables that can be measured: The capillary hydrostatic pressure is clinically measured as the pulmonary capillary wedge pressure (PCWP). The other variable that can be measured is colloid oncotic pressure (Πc). What are not measured are interstitial pressures, capillary

permeability, and the Staverman reflection coefficient for albumin, pulmonary lymph flow, interstitial space geometry, and compliance. • At the arterial end of a vessel, the hydrostatic pressure is greater than the osmotic pressure, so the net movement favors water and other solutes being passed into the tissue fluid. At the venous end, the osmotic pressure is greater, so the net movement favors substances being passed back into the capillary. This difference is created by the direction of the flow of blood and the imbalance in solutes created by the net movement of water favoring the tissue fluid. PHYSIOLOGY/PATHOPHYSIOLOGY

Clinical disturbances in body fluid are often described based upon the ECF condition. A few rules should also be considered: The 2 compartments are (almost) always in osmotic equilibrium; the components of the ICC do not cross the cell membrane (water does); and normal kidneys, hormone function, and thirst mechanisms will eventually reinstate homeostasis. • Hypo-osmotic expansion (excessive water intake): The primary disturbance is an increase in free water that will distribute throughout both spaces (increase ECF and ICF volume). It secondarily decreases the osmolality of both the ECF and ICF. • Hypo-osmotic contraction (salt wasting by the kidneys): The primary insult is a decrease in the ECF and ICF osmolality. Because water follows sodium, both ECF and ICF volume are also decreased secondarily. • Iso-osmotic expansion (isotonic crystalloid administration, congestive heart failure, renal disease): There is an increase in total body volume and osmoles; therefore, there is no change in the ECF or ICF osmolality, but the ECF and ICF volume increase. The interstitial space provides a “cushion,” with resultant edema. • Iso-osmotic contraction (hemorrhage, burns): The primary insult is a decrease in both total body volume and osmoles; therefore, there is no change in ECF or ICF osmolality. The ECF volume decreases primarily and can draw fluid from the interstitial and intracellular space in order to maintain perfusion and circulation to tissues (this ability is limited). • Hyperosmotic expansion (hypertonic saline, mannitol, hyperglycemia): The primary effect is an increase in total body osmoles with the ECF >>> ICF. As a result, the ECF volume increases from movement of water out of the ICC into the intravascular compartment. • Hyperosmotic contraction (insensible losses such as sweating, respiratory track evaporation): The primary insult is a loss of free water that will decrease both ECF and ICF volume by approximately 1,400 mL (~7 times the original infused volume). The secondary insult is an increase in osmolality, although there is no increase in total body osmoles. • Third space loss: Early work on this topic (1960’s) suggested that during major surgery or trauma there will be an internal redistribution of ECF that no longer participates in the maintenance of hemodynamic status or urine output. This so-called “third space” contributes to generalized tissue edema seen frequently after massive fluid loading. The composition of third space losses is equivalent to the ECF and electrolyte composition plus a

small amount of protein. This loss could be replenished by infusion of crystalloids such as lactated Ringer’s or normal saline. Third space loss depends on the severity of tissue damage, duration of tissue damage, and hypotension.

PERIOPERATIVE RELEVANCE

• Normal saline and lactated Ringer’s have a similar osmolality to the ECF; therefore, water distributes equally throughout the whole of ECF. Because ISF comprises 2/3rd of the ECF, most crystalloids are distributed to the ISF resulting in interstitial edema. • 5% dextrose is a hypo-osmolar solution with an osmolality around 270 Osm. With the metabolism of glucose, there is a decrease in the plasma osmolality and water uniformly distributes to all the compartments. Since the ICC is the largest, most of the water will enter into the cell and cause cellular edema. • Hypertonic saline: The osmolality is around 2,500 Osm compared to 290 Osm in the plasma. An infusion of 200 mL of 7.5% hypertonic saline would quickly expand the intravascular volume by a volume approximately 7 times the original infused volume. The mechanism by which hypertonic solutions increase plasma volume expansion is secondary to shifting of fluid mainly from the ICC (and to a smaller extent by the interstitial compartment). This concept has been used in the early management of hypovolemic shock. Intravascular volume increase lasts about 30–45 minutes. In order to prolong the effect of hypertonic saline, some clinicians use hypertonic saline with dextran to extend its effect. • Colloids: The addition of proteins with oncotic pressure (in an isotonic crystalloid solution) results in an increased plasma oncotic pressure. Colloids are capable of expanding the intravascular compartment by approximately 100–150%. A key benefit is the increase in plasma volume without concomitant interstitial expansion. • Hyperosmolar solutions: Mannitol and urea are therapeutically administered to draw water out of the ICC. Its mechanism of action relies on its inability to cross cell membranes, thus increasing the ECF osmolality preferentially. Mannitol is commonly administered for neurosurgical cases and increased intracranial pressure. In the event of a disrupted blood– brain barrier, the solution would be able to enter the cell and increase intracellular osmolality.

EQUATIONS

Fluid distribution in an 80 kg male: • Total body water = 80 × 0.6 = 48 L • Intracellular water (ICC) = 80 × 0.4 = 32 L • Extracellular water = 80 × 0.2 = 16 L • Interstitial fluid = 80 × 0.15 = 12 L • Plasma = 80 × 0.05 = 4 L GRAPHS/FIGURES See Table See Table

REFERENCE

1. Brandstrup B. Fluid therapy for the surgical patient. Best Pract Res Clin Anesthesiol. 2006;20:265–283. 2. Shields CJ. Towards a new standard of perioperative fluid management. Ther Clin Risk Manage. 2008;4:569–571.

3. Yeager MP, Spence BC. Perioperative fluid management: Current consensus and controversies. Semin Dial. 2006;19:472–479.

CLINICAL PEARLS

• During homeostasis, all of the body’s fluid compartments are in osmotic equilibrium. During transient changes, pathological or therapeutic, water moves based upon hydrostatic, oncotic, and osmotic forces. • Extracellular fluid (ECF) mainly comprises sodium, chloride, and bicarbonate ions. The ECF volume is proportional to the total sodium content. • The interstitial and intravascular compartments have similar ionic compositions; it varies mainly in the chloride and protein concentrations.

EXTRACORPOREAL SHOCKWAVE LITHOTRIPSY (ESWL) James J. Konvicka, MD

BASICS DESCRIPTION General

• Extracorporeal shockwave lithotripsy (ESWL) is a minimally invasive technique that was initially introduced in 1980 to treat calculi that cannot pass through the urinary tract. • It is the preferred technique by urologists for the treatment of renal stones, proximal stones, and midurethral stones. Benefits of ESWL over open and endoscopic (cystoscopic) techniques: – Rates of cure are equivalent. – Significant reduction in treatment costs – Minimally invasive • Methods to localize the stone: – Fluoroscopy, biplanar or monoplanar, can be used to visualize radio-opaque stones, and contrast dye can be injected into the ureter for radiolucent (uric acid) stones. – Ultrasonography can provide images of all types of stones that are large enough, but airfilled intestinal loops may limit visualization of ureteral stones. • Prior to the ESWL, cystoscopy with stent placement is commonly performed to facilitate the passage of stones through the ureters. • Stones are pulverized in vivo into reduced size fragments that can be expelled by the body spontaneously. – There is little difference in the density of soft tissues; as a result, shockwaves move through tissue with a minimal dissipation of energy. – At the interface of the stone and fluid, there is a significant difference in density, along with the concentration of the shockwaves in a focused area that provides a major dissipation of energy. – Fragmentation is due to this energy overcoming the tensile strength of the calculus. – The process is repeated until the stone is pulverized into fragments that are ideally <1 mm, allowing them to pass spontaneously and painlessly. • To avoid arrhythmias (R on T syndrome), shockwaves are synchronized and triggered by the EKG to occur 20 milliseconds after the R wave during the refractory period for older generation lithotriptors. Therefore, length of treatment was determined by heart rate. Newer units have been developed to deliver lower energy and function independent of the EKG. Position

• Supine, lithotomy; lateral decubitus and prone may be considered depending upon the stone location. • A small, water-filled drum or a cushion with a silicone membrane is placed next to the

patient’s skin and functions as the coupling medium, thereby avoiding immersion-related physiologic alterations. First-generation lithotriptors required the patient to be immersed in water as the coupling medium.

Incision

Ureteroscopy through the urethra is performed. Otherwise, no skin incision is required. Approximate Time

• Older lithotripters: 1,500–2,000 shocks that may be triggered by the EKG R wave. • In general, typically 35–45 minutes

EBL Expected Minimal

Hospital Stay

None; typically an outpatient procedure Special Equipment for Surgery

• Lithotriptor: Has 4 basic components—an energy source, focusing device, coupling medium, and stone localization system. • Ureteroscope • Fluoroscopy, ureteral contrast dye • Ultrasound

EPIDEMIOLOGY Prevalence

Annual incidence of urolithiasis is 16.4 per 10,000 in the US. Prevalence

• 3 times more common in men than in women • Peaks in the 3rd to 4th decade of life

Morbidity

1–4% develop stone fragment pileup in the ureter; risk increases for greater stone burdens (10% for stone collections >2.0 cm2). Mortality Minimal

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Shock wave movement and impact through cutaneous tissue and viscera cause most of the pain and discomfort during ESWL. • Minimizing patient movement and respiratory excursion is necessary to maximize stone damage, limit surrounding tissue damage, and decrease the length of the procedure.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Flank pain often mimicking appendicitis • Renal insufficiency or renal failure • Obstructed pyelonephritis or pyelitis

History

• Screening for contraindications – Absolute contraindications: Bleeding disorder or anticoagulation Pregnancy – Relative contraindications: Large calcified aorta or renal artery aneurysms Untreated urinary tract infections Pacemaker or AICD Neurostimulation implant Morbid obesity

Signs/Physical Exam Hematuria

MEDICATIONS

• Analgesics • Antibiotics to treat infections if present

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Pregnancy test • Urinalysis and urine culture • KUB for radio-opaque stones • CT scan for anatomic information • Pacemakers and defibrillators: Pacemakers are often converted to demand mode pacing because shock waves may be misinterpreted as a “sensed” signal and inhibit or trigger activity. Defibrillators may misinterpret the shock wave as an arrhythmia and inappropriately deliver a shock. Deactivation of either device should be in concordance with either the company or in-house device clinic to ensure that it is properly performed as well as appropriately “re-activated.”

CONCOMITANT ORGAN DYSFUNCTION

Renal insufficiency may be present if there is obstruction.

TREATMENT

PREOPERATIVE PREPARATION Premedications

• Topical application of local anesthetic cream to the skin area that contacts the shockwave tube may decrease the need for IV analgesics. • Anxiolytics and narcotics may be titrated to effect, as needed.

Special Concerns for Informed Consent

• In patients with pacemakers or defibrillators, discuss perioperative management. • In patients receiving deep sedation or neuraxial blocks, discuss reasonable sedation goals and the potential to convert to a general anesthetic.

Antibiotics/Common Organisms

• First choice is a fluoroquinolone or trimethoprim-sulfamethoxazole. • Alternatives: Aminoglycosides, aztreonam, ampicillin, first- or second-generation cephalosporin, or amoxicillin/clavulanate

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with endotracheal tube (ETT): Has the potential benefit of decreasing respiratory excursion of the diaphragm with inspiration and expiration as well as allowing brief periods of apneic oxygenation • General anesthesia with ETT and jet ventilator (jet adapter is attached to the ETT) may be used to decrease movement, the number of shocks delivered, as well as OR and anesthesia time. Drawbacks related to jet ventilation include: – Risk for barotrauma and hypercarbia – Inability to measure tidal volumes, FIO2

– Need for a total IV anesthesia technique (can actually increase anesthetic time and negate the potential decreased procedure time) • General anesthesia with laryngeal mask airway (LMA): Drawbacks include the potential for stomach and bowel insufflation that can impair visualization by the surgeon. An LMA with a port to place an orogastric tube may alleviate this problem. Additionally, spontaneous breathing may move the stone in and out of the shockwave zone (both inspiration and exhalation are active processes under general anesthesia). • Deep sedation: Advantages include the avoidance of airway instrumentation and faster recovery time. Drawbacks include difficulty with lying still, respiratory excursions that may move the stone in and out of the focal zone, and limitations of sedation during stimulating portions of the procedure (e.g., cystoscopy and stent placement). • Neuraxial anesthesia (T6 level is required): Epidural fluid boluses may cause an air–tissue interface in the epidural space; this can result in shockwaves causing damage in this area. A spinal technique may avoid this complication. Drawbacks include difficulty lying still and respiratory excursion moving the stone in and out of the focal zone. Additionally, the dermatomal level that is required (T6) can cause motor blockade of respiratory accessory muscles; patients with pulmonary disease may depend upon these muscles to maintain

adequate ventilation and oxygenation.

Monitors

Standard ASA monitors

Induction/Airway Management

• Prior to induction, the stone is usually localized and the patient is positioned. Prone and lateral positioning are done after induction. • Standard induction techniques

Maintenance

• General anesthesia is commonly maintained with volatile agents. When jet ventilation is utilized, a total intravenous technique needs to be utilized. • Ventilation – Spontaneous respiration may allow the stone to move in and out of shockwave field. This may prolong the treatment time. – Paralysis and controlled ventilation will allow brief apneic oxygenation and controlled respiratory excursion. – A low heart rate may increase the treatment time in older lithotriptors that fire after the R wave. – Fluoroscopy requires radiation safety.

Extubation/Emergence

There are no specific issues with emergence for this procedure.

FOLLOW-UP BED ACUITY

Recovery room followed by discharge home ANALGESIA

• Pain is typically mild and described as soreness. • Renal colic from stone fragment passage is not uncommon. • Thin patients may have more pain because the converging shockwave is concentrated at the point of skin penetration.

COMPLICATIONS

• Flank petechiae, hematuria, and passage of stone fragments with associated renal colic are common. • Perinephric hematoma • Acute and chronic hypertension • Bacteriuria and sepsis • Less common complications may include pulmonary contusion, hemoptysis, pancreatitis, splenic hematoma, elevated liver function tests (transient), and biliary colic with inadvertent fragmentation of adjacent biliary stones.

PROGNOSIS

• Depending on stone size, composition, and location, cure rates are >90%; however, stones may recur. • ESWL has a similar rate of success compared to other stone removal techniques.

ADDITIONAL READING

• Lee C, Weiland D, Ryndin I, et al. Impact of type of anesthesia on efficacy of medstone STS lithotripter. J Endourol. 2007;21(9):957–960. • Ozcan S, Yilmaz E, Buyukkocak U, et al. Comparison of three analgesics for extracorporeal shock wave lithotripsy. Scand J Urol Nephrol. 2002;36(4):281–285. • Pearle MS, Calhoun EA, Curhan GC, et al. Urologic diseases in America project: Urolithiasis. J Urol. 2005;173(3):848–857. • Sorensen C, Chandhoke P, Moore M, et al. Comparison of intravenous sedation versus general anesthesia on the efficacy of the Doli 50 lithotriptor. J Urol. 2002;168(1):35–37.

See Also (Topic, Algorithm, Electronic Media Element) • Cystoscopy • Radiation safety

CLINICAL PEARLS

• ESWLs are minimally invasive procedures that have reduced morbidity and mortality compared to open stone removal. • Older generation units may trigger off the R wave. • General endotracheal anesthesia with paralysis may be requested by surgeon.

F-INSPIRATORY

Debra Domino Pulley, MD

BASICS DESCRIPTION

• F-inspiratory (FI) is defined as the fractional percentage or relative concentration of a

specific gas in a mixture of inspired gases. – Varies between 0 and 100% – Commonly refers to oxygen (FIO2) but also applies to any gas that is inhaled by the

respiratory system such as nitrogen, nitrous oxide, and any volatile anesthetic gas – Inspiratory gases → alveoli → pulmonary capillaries → tissues (brain, fat, muscle, etc.). • FA is the fractional concentration of a gas in the alveoli.

• Partial pressure of a gas is the fractional amount of a gas times the barometric pressure. PA is the partial pressure of a gas in the alveoli.

PHYSIOLOGY PRINCIPLES

• Oxygen – FIO2:

Room air oxygen fraction is 21% at sea level. Intraoperatively, the fresh gas flows can be adjusted in relation to one another to attain the desired FIO2. The anesthesia machine displays the FIO2 of the fresh gas flow.

– Circuit: The fresh gas flow mixes with the exhaled gases. An oxygen analyzer in the breathing circuit thus measures the actual FIO2 that the patient receives.

– Alveoli: During inspiration, gases enter the body and travel to the lung. Water vapor is added to the inhaled gas, and at the alveolar level, the gas is maximally saturated. The partial pressure of water vapor at normal atmospheric pressures is 47 mm Hg. The partial pressure of oxygen in the alveoli cannot be easily measured, but it can be calculated using the alveolar gas equation: PAO2 = [FIO2 × (Patm - PH2O)] [PaCO2/RQ]. This requires only an arterial blood gas to measure PaCO2. The A-a

gradient is the difference between partial pressure of oxygen in the alveoli and partial pressure of oxygen in arterial blood. – Alveolar capillary membrane: Gas flows down an area of high to low partial pressure to attain equilibrium. Thus, oxygen moves from the alveoli to the pulmonary capillaries; at the same time, CO2 flows from the pulmonary capillaries into the alveoli and is eliminated with exhalation. Blood. After crossing the alveolar and capillary membranes, oxygen binds with hemoglobin and dissolves in the blood. The amount bound to hemoglobin is (1.36 × Hb

× SaO2)/100. At sea level, the amount dissolved is 0.0031 × PaO2. Blood oxygen

content is thus comprised of both values. Henry’s law states that the amount of dissolved gas will be proportional to the partial pressure. In a hyperbaric chamber, 100% oxygen is pressurized to 2 or 3 times the atmospheric pressure. Since the partial pressure increases 2 to 3 times, the amount of dissolved oxygen in the blood also increases. – Tissues: Oxygen is necessary at the cellular level for aerobic metabolism. An increase in demand results in a hypoxic state that facilitates gas flow down a partial pressure gradient. Additionally, changes in the metabolic environment (pH, etc.) cause a right shift in the oxygen–hemoglobin saturation curve and facilitate unloading to the tissues. • Volatile anesthetics – Vaporizer dials are set to deliver a specific fraction of gas into the fresh gas flow. This concentration can also be expressed as partial pressure: Pagent = FIagent × Patm. – Circuit: The fresh gas flow, at the specific volatile agent fraction, mixes with the exhaled gases. The gas analyzer in the breathing circuit allows a measure of the FIagent that is

actually being delivered to the patient. – Alveoli: The partial pressure of the inhaled anesthetic at the alveoli is the fraction times atmospheric pressure minus water vapor pressure. The minimum alveolar concentration (MAC) is the lowest alveolar (absolute) concentration to produce immobility to 50% of subjects at 1 atm (expressed as% atm). MAC values are indirectly measured by the end-tidal concentration (FEagent); there is no

current method to measure the alveolar concentration. The lower the MAC, the more potent the anesthetic. Nitrous oxide is one of the least potent anesthetics and has a MAC greater than 100%. It would need to be delivered in a hyperbaric chamber to be a complete anesthetic. When volatile agents are mixed, or more commonly when volatile agents are utilized with nitrous oxide, MAC values are additive. – FA/FI: As a volatile anesthetic is inhaled, the alveolar concentration (FA) will rise until it

reaches the inspired concentration (FI). The rate at which this occurs is determined by

several factors: Inspired concentration (FIagent)

Alveolar ventilation Opposing the increasing concentration of a gas is the uptake or absorption of the gas into the blood and tissues. Uptake is the product of 3 factors: solubility, cardiac output, and the difference (gradient) between mixed venous partial pressure and alveolar partial pressure – Tissues: The concentration of the inhaled anesthetic in a tissue is dependent upon the partial pressure and tissue solubility. The partial pressure of inhaled gases in the brain will determine the depth of anesthesia. • Concentration effect: Increasing the inspired concentration of a gas results in an increased alveolar concentration and also affects the rate of rise of FA/FI. This is due to a concentrating effect and an augmented inflow effect. • Second gas effect: Describes the concentration effect of one gas (nitrous oxide) upon another. High concentrations of nitrous oxide are usually delivered. At the time of

induction, rapid uptake of nitrous from the alveoli into the blood occurs to obtain equilibrium. This results in a decrease in alveolar volume and an increase in the concentration of other gases present in the alveoli.

ANATOMY

• The alveolus is the terminal end of a series of branching tubes from the trachea. It is where gas exchange occurs. • Capillaries form a dense network in the walls of the alveoli. – Capillary diameter is 10 microns. – Red blood cell diameter is 6–8 microns. • There is a very thin blood–gas barrier (<0.5 microns), and this includes a layer of surfactant, alveolar epithelium, interstitium, capillary endothelium, and plasma

DISEASE/PATHOPHYSIOLOGY

• Decreased FIO2 can result in hypoxemia, which is defined as an arterial PO2 <60 mm Hg. Methods to increase the FIO2 include:

– Nasal cannula: There is an approximately 4% increase in FIO2 for each liter per minute increase in flow. Thus, 2 L via NC is equivalent to approximately 29% FIO2.

– Simple mask: Covers the mouth and nose and decreases mixing with room air. With exhalation, 1-way valves decrease rebreathing of carbon dioxide. It is suggested that at least 4 L/min should be used to avoid rebreathing of carbon dioxide. An FIO2 of

approximately 40–50% can be delivered. – Nonrebreather mask: In addition to covering the mouth and nose, the reservoir bag contains approximately 1.5 L of oxygen. With inspiration, gas from the bag is preferentially taken up. With exhalation, 1-way valves decrease rebreathing of carbon dioxide. This allows for the delivery of an FIO2 of 60–90%.

– Trach collar: Used for patients with a tracheostomy; it is similar to a simple mask, except it fits over the ostomy. – At higher elevations, barometric pressure will decrease. The fractional component of oxygen does not change, but the partial pressure will decrease. – Hyperbaric oxygen treatment has been useful in situations when the delivery of oxygen to tissues from hemoglobin is inadequate. Per Henry’s law, increasing the atmospheric pressure will increase the amount of oxygen dissolved in the blood. These include Profound anemia Carbon monoxide poisoning Failing skin grafts and flaps Infections Traumatic injury Radiation necrosis Non-healing wounds • High FIO2 may cause – “Absorption” atelectasis: Nitrogen is a relatively insoluble gas in blood, and thus serves as an alveolar “filler” (prevents collapse of alveoli). Thus, in the absence of nitrogen, oxygen

absorption can result in complete absorption (into the pulmonary capillaries) of gas contained in the alveoli (particularly in marginally ventilated alveoli). – Acute lung injury from mild tracheobronchitis to diffuse alveolar damage – Decrease in ventilation and accumulation of carbon dioxide in patients with COPD – Retinopathy in the newborn • Increasing FIO2 at higher levels of shunt will not (or only minimally) decrease the A-a gradient

PERIOPERATIVE RELEVANCE

• In the perioperative setting, different compositions of gases enter the body. These include oxygen, air (oxygen and nitrogen), nitrous oxide, helium, and volatile anesthetics such as isoflurane, sevoflurane and desflurane. • Significant morbidity and mortality (including hypoxic brain injury) can occur when inadequate oxygen is delivered to a patient. Safety mechanisms have involved changes in design to decrease the incidence of delivering a low oxygen mixture or the wrong gas to a patient. They include: – Multiple oxygen sources: Pipeline supply, cylinder supply, auxiliary oxygen supply – Gas specific systems: Diameter indexed safety system, pin index system – Oxygen supply and pressure alarms: Fail safe valve, pressure regulators – Oxygen/nitrous oxide proportioning systems – Inspired oxygen concentration monitor • Exhausted CO2 absorbent can lead to inspired CO2 and a decreased FIO2. • Treatment strategies when hypoxia occurs include: – Increasing the inspired oxygen concentration prior to induction when apnea will occur – Administering oxygen immediately after cessation of N2O to eliminate diffusion hypoxia.

• Different mechanisms of perioperative hypoxia can be distinguished by calculating the (Aa)O2 gradient.

• Onset and emergence: Can be hastened by changing the concentration, increasing ventilation, using an anesthetic that is less soluble, and increasing the fresh gas flow. • Aerosolized drugs that are inhaled such as albuterol, prostacyclin, corticosteroids, and racemic epinephrine are liquids and do not enter the bloodstream via gas exchange

EQUATIONS

• Dalton’s law of partial pressure – the total pressure of a mixture of gasses is equal to the sum of the partial pressure of each gas – PT = P1 + P2 + P3 +… + Pn • PI = FI × Patm, where PI is the partial pressure of inspired gas, FI is the fraction of inspired gas, and Patm is the atmospheric pressure.

• Alveolar gas equation – the partial pressure of oxygen in the alveoli – PAO2 = [FIO2 × (Patm – PH2O)] – PaCO2/RQ – Typically, Patm = 760 mm Hg, PH2O = 47 mm Hg, and RQ = 0.8

– PAO2 = (FIO2 × 713) – (PaCO2/0.8)

– A-a gradient – the difference between alveolar and arterial O2 – A-a gradient = PAO2 – PaO2

• Oxygen content of blood – CaO2 = (1.36 × Hb × SaO2/100) + (0.0031 × PaO2) GRAPHS/FIGURES

FIGURE 1. Rate of rise of anesthetic gas. There is an initial rapid rise, which slows with time as equilibrium between the

input and uptake from the alveoli occurs. Soluble anesthetics have greater uptake by the blood and thus take longer to reach equilibrium. Conversely, poorly soluble inhaled agents quickly reach equilibrium.

REFERENCES

1. Yasuda N, Lockhart SH, Eger El II, et al. Comparison of kinetics of sevoflurane and isoflurane in humans. Anesth Analg. 1991;72:316–324. 2. Yasuda N, Lockhart SH, Eger El II, et al. Kinetics of desflurane, isoflurane, and halothane in humans. Anesthesiology. 1991;74:489–498. 3. Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. NEJM. 1996;334:1642–1648. 4. Benoit Z, Wicky S, Fischer JF, et al. The effect of increased FIO2 before tracheal extubation on postoperative atelectasis. Anesth Analg. 2002;95:1777–1781. 5. Edmark L, Auner M, Enlund M, et al. Oxygen concentration and characteristics of progressive atelectasis formation during anaesthesia. Acta Anaesthesiol Scan. 2011;55:75– 81. See Also (Topic, Algorithm, Electronic Media Element) – Blood oxygen carrying capacity – Supplemental oxygen

CLINICAL PEARLS

– Delivery of the inhaled anesthetic will be more rapid with increased concentration of inhaled anesthetic, increased fresh gas flow, and increased alveolar ventilation.

– Emergence from anesthesia will be more rapid with lower solubility anesthetics, increased alveolar ventilation, and increased fresh gas flow. – High inspired concentration of oxygen before induction and during emergence can increase atelectasis. – Hypoxemia with normal A-a gradient is caused by alveolar hypoventilation. – Hypoxemia with increased A-a gradient is caused by V/Q mismatch, shunt, and/or impaired diffusion. – Postanesthesia, hypoxemia occurs frequently and supplemental oxygen may be required.

FACET JOINT INJECTIONS, LUMBAR Zachary M. Zumbar, MD, MPH Beth H. Minzter, MD, MS, FIPP

BASICS DESCRIPTION

• Facet joint disease, also known as zygapophysial arthropathy, is a common cause of back pain. • Lumbar facet arthropathy accounts for 15–40% of cases of chronic low back pain. The exact prevalence is uncertain because most studies excluded patients with radicular symptoms or prior back surgery. PHYSIOLOGY PRINCIPLES

Facet joints are a junction or pivot point between bony levels of the spine; movement (and limits to motion) is the result of rotation around this joint (akin to railroad tracks). • Cervicals: Joints in the upper cervical spine face backward, upward, and medial (pneumonic: BUM), whereas the joints in the lower cervical spine face forward, downward, and lateral (pneumonic: FDL). The atlanto-occipital joint is responsible for flexion– extension; the atlanto-axial joint is responsible for rotation; and the joints from C2 to C7 are responsible for smaller levels of flexion–extension, rotation, and lateral bending. • Thoracic: Backward, upward, and lateral (pneumonic: BUL). The axis of rotation is at the center of both the vertebral body and the disc. As such, the discs experience rotation torsion but minimal shearing forces. Consequently, the upper thoracic vertebrae (T1–T10) offer great rotational motion range (∼35° to the left or right) and are mainly constrained by ligamentous attachments and the costal cage. • Lumbar: Backward and medial; they face each other (pneumonic: BM). As a result of their orientation, the axis of rotational motion is at the base of the spinous process. The disc experiences greater shearing forces (the disc and vertebral body must slide past one another in opposite directions) that severely limit rotation compared to the upper thoracics. Their rotation is ∼5° to the left or right, whereas they are capable of forward and backward bending. The upper lumbar facet joints are oriented more parallel to the sagittal plane, whereas the lower lumbar facet joints are oriented more parallel to the coronal plane. ANATOMY

• The paired facet joints join the vertebral arches of 2 adjacent vertebrae along the posterolateral spine. • They are true synovial joints with a synovial membrane, hyaline cartilage, and a fibrous capsule containing 1–1.5 mL of synovial fluid. • Posteriorly, the joint capsule is continuous with the multifidus muscle. • Anteriorly, the capsule is continuous with the ligamentum flavum. • The innervation of each facet joint comes from the medial branches of the dorsal ramus at

the same level and one level above the respective joint.

DISEASE/PATHOPHYSIOLOGY

• Causes of facet joint pain include: – Recurrent strain and low-grade trauma (responsible for most cases of facet joint pain) – Lateral bending causes the greatest strain on the L1–2, L2–3, and L3–4 facet joint capsules. – Forward flexion causes the greatest strain on the L4–5 and L5–S1 facet joint capsule – Acute trauma – Rapid deceleration injuries can result in dislocation. • Predisposing factors to facet joint pain: – Osteoarthritis – Inflammatory arthritides – Synovial impingement – Synovial inflammation – Synovial cysts in the facet joint – Meniscoid entrapment – Chondromalacia facetae – Pseudogout – Villonodular synovitis – Infection • Findings on history: – Lumbar facet pain from any level may radiate into the groin. – Pain from upper lumbar segments can radiate into the flank, hip, and upper lateral thigh. – Pain from lower lumbar segments tends to radiate deeper into the thigh, usually laterally or posteriorly. – Facet joint pain rarely radiates below the knee, though pathologic changes in the joint may cause foraminal stenosis resulting in radicular symptoms distinct from the joint pain itself. • Physical examination findings: – Individual studies have shown findings of paraspinal tenderness or pain reproduction with either forward flexion or extension–rotation on physical examination in patients with block-confirmed facet pain. – However, other studies have found that a positive response to diagnostic blocks is associated with the absence of pain exacerbation with forward flexion or extension– rotation. • Diagnosis: – A positive response to a diagnostic block is the standard for diagnosis. Medial branch blocks and intraarticular injections are considered to be equally efficacious for diagnosis, and there is no strong evidence of the superiority of one to the other. – No set of history and physical examination findings has been found to be diagnostic for facet joint pain. – Degenerative changes can be seen on radiologic imaging but do not reliably correlate with facet joint pain. CT and MRI findings have not been consistently shown to correspond with response to diagnostic blocks. • Spondylolysis is the result of weakness or stress fracture in the pars interarticularis that

connects the upper and the lower segments of the facet joints. It is most commonly seen at the L4 and L5 level. • Spondylolisthesis describes vertebra slipping out of the proper position onto the bone below it. It can result from spondylolysis, congenital causes, or degeneration. In degenerative spondylolisthesis, aging results in the discs losing water, which makes them less capable of resisting vertebra movement. If the bone presses on a nerve, it manifests as pain.

PERIOPERATIVE RELEVANCE

• Conservative therapies for facet joint disease: – Physical therapy – Osteopathic manipulation – Acupuncture – NSAIDs and acetaminophen – SNRI and tricyclic antidepressants – Psychological counseling for coping skills • Invasive therapies include intraarticular steroid injections, radiofrequency denervation, cryodenervation, and phenol neurolysis. • Intraarticular steroid injections have shown inconsistent outcomes. Conclusions of some studies indicate that injections do not provide statistically significant benefit while others have shown that they can provide intermediate-term relief (3–6 months). Complications are rare but can include infections, spinal anesthesia, and postdural puncture headache. • Radiofrequency ablation/denervation (RFA) has shown variable outcomes as well. Among the confounding issues of those that failed to show benefit are suboptimal needle placement and not selecting candidates through the use of diagnostic blocks. The most methodologically well done studies have shown significant pain relief lasting from 6 months to >1 year. Complications can include transient numbness, paresthesias, and neuritis. • Techniques for needle placement and radiofrequency ablation are similar. – Fluoroscopic guidance is utilized and sterile technique must be maintained. With the patient prone, an AP view of the target joint is obtained. – The L5 dorsal ramus can be approached from this view, the target point of which is the junction of the sacral ala and the superior articular process. – For lumbar levels cephalad to the sacral ala, the C-arm is rotated obliquely, approximately 15–20° until a clear view of the joint is obtained. This is sometimes referred to as the “Scottie-dog” view. The target for needle placement is the junction of the superior articular process and the transverse process. A 25-gauge needle is advanced into the joint, until it contacts bone. Confirmation of needle position can be made with AP and lateral views. – A small amount of contrast is injected to confirm intraarticular spread. Then 0.5–1 mL of injectate containing steroid, with or without local anesthetic, is injected into the joint. While injecting contrast or steroid mixture, care should be taken to ensure that the integrity of the joint capsule is not disrupted. – For RFA, a 18- to 22-gauge radiofrequency cannula with a 10-mm active tip should be used for each level. The target point for RFA is also the junction of the superior articular process and the transverse process or sacral ala, depending on the level. However, since the radiofrequency lesion extends radially from the electrode, the cannula should lie along

the lateral aspect of the superior articular process just above its junction with the transverse process or sacral ala. This placement can be facilitated with a slight caudal tilt of the C-arm prior to starting. After proper placement is confirmed with AP and lateral imaging and test stimulation, ablation can commence. • Other treatments that have been used include pulsed radiofrequency denervation, cryodenervation, and phenol neurolysis. • Surgical intervention: There is little evidence to support surgical intervention for chronic lumbar facet arthropathy. Additionally, diagnostic facet blocks do not improve surgical outcomes.

GRAPHS/FIGURES

REFERENCES

1. Cohen SP, Hurley RW. The ability of diagnostic spinal injections to predict surgical outcomes. Anesth Analg. 2007;105:1756–1775. 2. Cohen SP, Raja SN. Pathogenesis, diagnosis, and treatment of lumbar zygapophysial (facet) joint pain. Anesthesiology. 2007;106:591–614. 3. Dreyfuss P, Halbrook B, Pauza K, et al. Efficacy and validity of radiofrequency neurotomy for chronic lumbar zygapophysial joint pain. Spine. 2000;25:1270–1277. 4. Ianuzzi A, Little JS, Chiu JB, et al. Human lumbar facet joint capsule strains: I. During physiological motions. Spine J. 2004;4:141–152.

5. van Kleef M, Barendse GA, Kessels A, et al. Randomized trial of radiofrequency lumbar facet denervation for chronic low back pain. Spine. 1999;24:1937–1942.

ADDITIONAL READING

• Benzon HT, Rathmell JP, Wu CL, et al., eds. Raj’s practical management of pain, 4th ed. Philadelphia, PA: Mosby/Elsevier, 2008. • Raj PP, Lou L, Erdine S, et al., eds. Interventional pain management: Image-guided procedures, 2nd ed. Philadelphia, PA: Saunders Elsevier, 2008. • Rathmell JP. Atlas of image-guided intervention in regional anesthesia and pain medicine and complications in regional anesthesia and pain medicine. Philadelphia, PA: Lippincott Williams & Wilkins, 2006.

See Also (Topic, Algorithm, Electronic Media Element) • Epidural steroid injections • Sacroiliac joint injections

CODES ICD9 716.98 Arthropathy, unspecified, other specified sites ICD10 M12.08 Chronic postrheumatic arthropathy [Jaccoud], vertebrae

CLINICAL PEARLS

• The lumbar facet joints are a common source of low back pain. • Local anesthetic blocks are the only reliable method for diagnosing facet joint pain. • Both conservative and invasive therapies are available to treat facet joint pain.

FAT EMBOLUS SYNDROME Andrea Parsons, MD

BASICS DESCRIPTION

• Fat embolus is the presence of fat droplets within the peripheral and lung microcirculation. It most commonly occurs with long shaft bone (femur, tibia, radius, ulna, rib) or pelvic fractures, but is also seen with joint arthroplasty, liposuction, and bone marrow transplants. • Fat emboli syndrome (FES) is a rare and life-threatening consequence of fat emboli with a classic triad of hypoxemia, delirium, and petechial rash that presents 24–72 hours after fracture or surgical procedure. • Early diagnosis and support of pulmonary and cardiac systems may improve prognosis.

EPIDEMIOLOGY Incidence

• Epidemiologic values may underestimate true numbers since diagnosis lacks specific laboratory tests or studies (1). • Isolated fractures of any long bone (femur, tibia, radius, rib, etc.): 0.1% or 1 in 1,000 patients • Multiple fractures of unilateral femur: 1.2% • Bilateral femurs: up to 33% • Liposuction: 19 in 100,000

Morbidity

• Mechanical obstruction can cause distal ischemia. • Paradoxical embolus can result in a cerebral or myocardial ischemic event. • Inflammatory response can result in hypoxia, heart failure, or cerebrovascular accident.

Mortality

• Large emboli can quickly progress to death despite adequate resuscitation. • Fulminant FES: As high as 10–45% (2) • Liposuction: 8.5% (3) ETIOLOGY/RISK FACTORS

• Fat embolism most commonly occurs when endogenous fat is released from a tubular (long shaft) bone or pelvic fracture into the circulation. Exogenous lipid emulsions injected into the circulation can also cause fat embolism (1). • Risk factors include: – Long bone fractures (femur, tibia, radius, ulna, rib): Closed fractures have a higher incidence than open fractures. – Pelvic fractures: Closed fractures show higher incidence than open fractures.

– Orthopedic procedures (joint arthroplasty) – Soft-tissue injuries – Liposuction – Bone marrow harvesting/transplant – Bone tumor lysis – Lipid infusions

PHYSIOLOGY/PATHOPHYSIOLOGY

• Fat embolus is distinct from fat embolus syndrome. Fat embolus describes the presence of fat globules in systemic and pulmonary circulations and is often asymptomatic. On the other hand, FES is a clinical consequence of fat embolus and manifests as a triad of: – Pulmonary changes (shortness of breath, hypoxemia) – Cerebral dysfunction (agitation, delirium, coma) – Petechial rash (only in 20–50% of cases) • The factors which predispose a patient to the development of this rare and life-threatening syndrome remain unclear. Although fat emboli are present in several patients with long bone fractures, only 1–3% develop FES. There is an increased incidence with multiple fractures and bilateral injuries, suggesting the quantity of fractures may play a role. • Pathophysiology involves inflammatory and mechanical manifestations: – Inflammatory: In patients who develop FES, the breakdown of embolized fat into free fatty acids has been linked to the development of acute respiratory distress syndrome (ARDS) and cardiac dysfunction. Injury of vascular endothelium can lead to inflammatory pathway activation via endothelin-1, fibrin, neutrophils, etc. Activation of this pathway can result in pulmonary vasoconstriction (pulmonary hypertension), increased vascular permeability (pulmonary edema), platelet aggregation (thrombocytopenia), and V/Q mismatch (hypoxemia). – Mechanical: Embolized fat travels to the right heart causing increased pulmonary artery and right heart pressures. This can lead to right heart strain (increased central venous pressure, jugular venous distension, peaked T waves) and decreased cardiac output (increased wedge pressure, decreased MVO2, hypotension). Significant right ventricular outflow tract obstruction can lead to right heart failure, cardiovascular collapse, and/or death. • Mechanical/traumatic etiologies: Occurs when bone marrow or adipose tissue is forced into venules, which occurs with traumatic injury (fractures, liposuction, etc.). With bone fractures, fat enters venules that are held open by osseous attachments. • High intramedullary pressures: The reaming of the bone shaft, bone cement application, or prosthetic placement can cause the extrusion of fat from the bone marrow into the circulation. • Nontraumatic: Occurs with lipid agglutination in critically ill patients receiving nutritional fat emulsions. • Paradoxical embolism: Fat can also pass from the right to left side of the heart through a patent foramen ovale and may result in a cerebral or myocardial infarction. Patent foramen ovale can be present in 20–30% of the general population.

PREVENTATIVE MEASURES

• Early immobilization of bone fractures reduces the risk of FES. Operative reduction further reduces the risk, as opposed to conservation measures (e.g., traction). • Although still controversial, some evidence suggests that steroids given prophylactically in the emergency department reduce the incidence of fat embolism. • Surgical techniques to limit the increase in intraosseous pressures in cases involving bone cement: Cleaning the bone to remove debris and marrow prior to bone cement placement, creating a venting hole in the bone, and/or allowing the bone cement to become viscous before applying.

DIAGNOSIS • Clinical diagnosis: Guidelines for diagnosing fat embolism syndrome include one sign from the major criteria category and 4 signs from the minor criteria category (4). – Major criteria: Petechiae in a vest distribution Hypoxemia with PaO2 <60 mm Hg, FIO2 >0.4

Central nervous system depression disproportionate to hypoxemia Pulmonary edema – Minor criteria: Tachycardia (heart rate >110 beats per minute) Pyrexia (temperature >38.5°C) Emboli visible in retina Fat in urine Fat in sputum Unexplained drop in hematocrit or platelet count Increasing erythrocyte sedimentation rate • V/Q mismatch (ventilation/perfusion ratio). – Low V/Q ratio (shunt) indicates impaired ventilation with respect to perfusion; can occur with FES if pulmonary edema or ARDS is present (inflammatory). – High V/Q ratio (dead space) indicates impaired perfusion with respect to ventilation; can occur with FES as the fat emboli impair blood flow through the lung (mechanical). • ECG: New right bundle-branch block or nonspecific T-wave changes. • Thrombocytopenia can occur with the consumption of platelets. Anemia and low fibrinogen levels can also be present. • Transesophageal echocardiography can show evidence of emboli in the right ventricle, but it is more useful to assess volume status and cardiac function if circulatory collapse is imminent. • A late laboratory marker of FES is serum lipase, which becomes elevated 3 to 5 days after embolization and peaks at 5 to 8 days. • Histology: Fat globules in vascular spaces • Over time, chest radiography can show evolution of ARDS infiltrates.

DIFFERENTIAL DIAGNOSIS • Acute coronary syndrome

• Cardiogenic shock • Thromboembolus • Thrombotic thrombocytopenic purpura • Bone cement implantation syndrome: Hypotension associated with the use of polymethylmethacrylate or bone cement

TREATMENT • Repair of orthopedic and soft-tissue injury should be performed promptly. Consider continuous pulse-oximetry perioperatively in high-risk patients (long shaft bone fractures). • The mainstay of treatment is supportive therapy. Use advanced cardiac life support (ACLS) guidelines when necessary. • Maintain oxygen saturation >90% in order to optimize tissue oxygenation. Administer supplemental oxygen and consider intubation with mechanical ventilation if increased FiO2 and positive end-expiratory pressure (PEEP) is needed. • Monitor hemodynamics closely to optimize tissue perfusion. Use fluids and vasopressors as needed. Ephedrine, epinephrine, norepinephrine, and dobutamine can provide inotropic support to a failing right heart. • Treat anemia and coagulopathy appropriately.

FOLLOW-UP • Close postoperative monitoring; pulse oximetry • Patients may require mechanical ventilation or other support (i.e., continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP]).

CLOSED CLAIMS DATA

• Femur fractures are the most frequent cause of lawsuits for orthopedic surgeons. In adults, the most common complications include poor technique, infection, wrong-site surgery, fat and/or pulmonary embolus, and delay in diagnosis or treatment. – 32% of all claims involving femur fractures resulted in payments (n = 820). – Payment average: $113,000

REFERENCES

1. Stein PD, Yaekoub AY, Matta F, et al. Fat embolism syndrome. Am J Med Sci. 2008;336(6):472–476. 2. Huber-Lang M, Brinkmann A, Straeter J, et al. An unusual case of early fulminant posttraumatic fat embolism syndrome. Anaesthesia. 2005;60(11):1141–1143. 3. Grazer FM, DeJong RH. Fatal outcome from liposuction: Census survey of cosmetic surgeons. Plast Reconstr Surg. 2000;105:436–446. 4. Gurd AR, Wilson RI. The fat embolism syndrome. J Bone Joint Surg Br. 1974;56B:408–416.

ADDITIONAL READING

• American Academy of Orthopaedic Surgeons. Managing orthopaedic malpractice risk, 2nd ed. 1999. • Johnson MJ, Lucas GL. Fat embolism syndrome. Orthopedics. 1996;19:41–48.

See Also (Topic, Algorithm, Electronic Media Element) • Bone marrow transplant • Dead space

CODES ICD9

958.1 Fat embolism ICD10 • T79.1XXA Fat embolism (traumatic), initial encounter • T79.1XXD Fat embolism (traumatic), subsequent encounter • T79.1XXS Fat embolism (traumatic), sequela

CLINICAL PEARLS

• Fat embolus is distinct from fat embolus syndrome. • The pathophysiology of FES is composed of mechanical obstruction, injury related to free fatty acids, and endothelial injury causing activation of inflammatory pathways. • The classic triad of pulmonary changes, cerebral dysfunction, and petechiae suggest FES. However, it should be suspected in a trauma patient with V/Q mismatch, especially when there is no other pulmonary injury (e.g., pulmonary contusions). • Treatment is supportive including ACLS guidelines.

FEMORAL NERVE BLOCK Angela T. Hsu, MD

BASICS DESCRIPTION

• The femoral nerve consists of motor and sensory innervations to the anteromedial thigh and medial leg. • The femoral nerve block is a superficial regional block that is easy to perform and has a very high success rate. When combined with a sciatic nerve block, almost complete anesthesia and analgesia can be provided to the entire lower extremity below midthigh. PHYSIOLOGY PRINCIPLES

Local anesthetics bind to intracellular fast sodium channels and prevent nerve impulse initiation and propagation. ANATOMY

• The femoral nerve is formed from the dorsal divisions of the L2–L4 ventral rami, within the psoas muscle. • The femoral nerve emerges distally from the lateral border of the psoas muscle and descends in the groove between the psoas and the iliacus muscles. • Below the inguinal ligament, the femoral nerve is located lateral to the femoral artery and deep to the fascia lata and fascia iliaca. It is separated from the femoral artery by a portion of the psoas muscle which explains why a blind paravascular injection does not lead to local anesthetic spread to the femoral nerve.

• The femoral nerve divides into anterior and posterior divisions. – Anterior division: Medial cutaneous nerve, intermediate cutaneous nerve, and muscular branches Motor: Sartorius and pectineus muscles Sensory: Anterior and medial thigh – Posterior division: Saphenous nerve, muscular and articular branches Motor: Quadriceps muscle (rectus femoris and vastus intermedius, lateralis, and medialis) Sensory: Medial aspect of the lower leg – Functional innervation: Dermatomal innervation: Skin of anteromedial thigh, knee, medial aspect of the lower leg to medial malleolus Myotomal innervation: Sartorius, pectineus, and quadriceps femoris muscles (rectus femoris and vastus intermedius, lateralis, and medialis) Osteotomal innervation: Anterior hip joint, anterior femur, and anteromedial knee joint

PERIOPERATIVE RELEVANCE

• Blocks of the lower extremity are gaining popularity with the advent of ultrasound guidance. • Femoral nerve block ± other lower extremity blocks can provide anesthesia for lower extremity surgery when centroneuraxial blocks are contraindicated due to anticoagulation or undesirable because of a sympathectomy. • Even with anticoagulation, rarely is a femoral nerve block associated with significant

hematoma. • Indications – Analgesia: Femoral neck or shaft fracture Total hip arthroplasty Total knee arthroplasty Anterior cruciate ligament (ACL) repair – Surgical anesthesia Saphenous vein stripping Knee arthroscopy Femoropopliteal bypass surgery Quadriceps muscle biopsy Skin graft anterior thigh • Contraindications (relative): – Presence of prosthetic femoral artery graft – Situations in which dense sensory blockade could mask the onset of compartment syndrome • Complications (rare): – Hematoma – Local infection – Intraneural injection – Fall risk if patient ambulates before block resolution – Local anesthetic toxicity Central nervous system: Tinnitus, confusion, metallic taste in the mouth Cardiac: Tachycardia, hypertension, arrhythmia • Medication selection: – Choice of local anesthetic, concentration, ± epinephrine, and volume depends on whether the block will be used for analgesia or surgical anesthesia. With ultrasound-guided blocks, as little as 10 mL can be used. Analgesia: 10–15 mL of 0.5% ropivacaine or 0.25% bupivacaine can last for 5–12 hours. For longer coverage (12–30 hours), 15–30 mL may be used. Surgical anesthesia: 15–20 mL of 1.5% mepivacaine with 1:400,000 epinephrine can last for 3–4 hours. For longer cases, 15–20 mL of 0.5% ropivacaine with epinephrine or 0.5% bupivacaine can last for 5–7 hours. • Nerve stimulator technique: – Patient position: Supine – Equipment: Standard monitors Nearby resuscitative equipment A 5 cm, 22 gauge insulated needle Nerve stimulator set to deliver current at 1.0 mA, frequency 1 Hz, and pulse duration of 0.1 msec. – Palpate the femoral artery along the inguinal crease. The femoral nerve usually lies 1–2 cm lateral to the artery; thus to maintain this spatial distance, the needle should be

inserted at the same angle as the patella. The needle can be inserted 1 cm above or below the inguinal crease with a 30- to 45° cephalad tilt. Above the crease, the femoral nerve is more compact and usually has not divided into its branches and for this reason may be a more desirable approach. – The needle is advanced until a twitch of the patella (quadriceps) is elicited. If the twitch is maintained after turning down the nerve stimulator to 0.5 mA, a slow injection of local anesthetic is started. • Ultrasound technique: – Patient position: Supine – Equipment: Standard monitors and nearby resuscitative equipment A 5 cm, 22 gauge insulated needle Ultrasound with linear probe and the transducer set at high frequency (8–15 Hz) to locate the relatively superficial femoral nerve. – With the ultrasound probe, first identify the femoral vessels, noting the vein is collapsible. – From medial to lateral: Femoral vein → artery→nerve – From superficial to deep: The fascia lata is first encountered, then the fascia iliaca, and then the femoral nerve lying superficial to the iliopsoas muscle. – The femoral nerve will often appear as a triangular or flat hyperechoic (white) structure.

Image, with permission, by Dr. Christine Chavez.

Out of plane needle technique: Insert needle perpendicular to transducer from caudad to cephalad. In this case, only a cross section of the needle shaft (small dot) is visible on ultrasound image. It is difficult to track the location of the needle tip with this technique. Combining this technique with a nerve stimulator is recommended. Aim for a patellar twitch in order to assess correct needle tip depth. – In plane needle technique: The needle is inserted from lateral to medial in plane with the ultrasound beam. This technique allows for visualization of the needle tip. Depending on the depth of the nerve, a longer needle may be required.

Image, with permission, by Dr. Christine Chavez.

ADDITIONAL READING

• Murray JM, Derbyshire S, Shields MO. Lower limb blocks. Anaesthesia. 2010;65(1):57–66. • Szucs S, Morau D, Iohom G. Femoral nerve blockade [Review]. Med Ultrason. 2010;12(2):139–44. • ranco CD. Chap. 7, Regional Book. JHS Hospital of Cook County, 2009.

See Also (Topic, Algorithm, Electronic Media Element) • Local anesthetic toxicity • Sciatic nerve block

CLINICAL PEARLS

• For nerve stimulator technique: – Stimulation of the sartorius muscle (band of muscle from superior–lateral to inferior– medial thigh) without a patellar twitch should not be accepted. The sartorius muscle is innervated by anteromedial branches of the femoral nerve and one cannot be sure if the branches lie within or outside the femoral nerve sheath. Withdraw the needle and redirect laterally and slightly deeper. – Local muscle stimulation of psoas or pectineus muscles means the needle is too deep. Withdraw needle and redirect. – Vascular puncture means the needle is too medial. Withdraw needle, hold pressure, and then reinsert 1 cm laterally. – If the needle is inserted and produces no twitches, reassess landmarks and work progressively laterally from femoral artery. Reassess that the needle angle is parallel with that of the patella. – In obese patients, where the femoral artery is difficult to palpate and ultrasound is not available, consider the use of a Doppler to localize the arterial pulsations. • For ultrasound technique: – Although ultrasound guidance has the potential to minimize complications, both intravascular injection and intraneural injection have been reported despite its use. Be vigilant for detecting signs of intravascular injection.

FETAL CARDIOVASCULAR PHYSIOLOGY Richard C. Month, MD

BASICS DESCRIPTION

• Fetal circulation is primarily a series circuit as opposed to the parallel pulmonary and systemic circuits of the infant and adult. • In utero, the right ventricle (RV) is the primary systemic ventricle, with the left ventricle (LV) acting mainly to pump comparatively “highly” oxygenated blood to the coronary arteries and brain (1). • This is created by a series of shunts: – The ductus venosus (DV) shunts oxygenated blood from the umbilical vein (UV) into the inferior vena cava (IVC), bypassing the liver. – The ductus arteriosus (DA) shunts blood from the pulmonary arteries into the descending aorta, bypassing the lungs, head, and upper extremities. – The foramen ovale (FO) shunts blood from the right atrium (RA) into the left atrium, bypassing the lungs. • The low-resistance placenta acts as the gas exchange organ while the high-resistance pulmonary circulation is mainly bypassed.

PHYSIOLOGY PRINCIPLES

• In utero physiology is structured to maximize oxygen delivery to the brain and heart in the comparatively hypoxic fetal environment. • Simultaneously, maintenance of this fetal environment is dependent on this degree of hypoxia. – Hypoxia decreases nitric oxide production with resultant hypoxic pulmonary vasoconstriction. The high pulmonary artery pressures lead to increased right heart pressures that maintain the right-to-left shunt through the FO. – Hypoxia also leads to increased circulating prostaglandins, which maintain the patency of the DA and the DV. • Delivery is marked by rapid and profound changes in this circulation that start the transition to normal extrauterine circulation. These changes may take as long as several days to complete.

ANATOMY

• Normal in utero circulation (1): – Starting in the placenta, oxygenated blood is returned to the fetal circulation via the UV. – The majority of this oxygenated blood is shunted around the liver through the DV into the IVC and right atrium. – 40% of the blood returning via the IVC crosses the FO into the left atrium LA. – This blood enters the LV and is pumped into the ascending aorta. 70% of this blood flows

to the upper extremities and brain (relatively well-oxygenated), returning to the RA via the superior vena cava (SVC). – SVC blood return enters the RA and is preferentially directed across the tricuspid valve into the RV. Only 10% of the blood returning into the SVC will cross the FO. – Blood then travels into the PA, where 90% is shunted via the DA into the descending aorta. – About 40% of total cardiac output is then returned to the placenta via the umbilical arteries (remaining flows to the lower extremities and organs). • Normal transition to extrauterine life (2): – Rapid changes in right and left heart pressures lead to decreased shunting. With the clamping of the umbilical cord, the low-pressure placenta is removed from the neonate’s circulation. The resultant increase in neonatal afterload increases pressure in the left heart. Simultaneously, as the neonate takes its first breath, circulating oxygen tensions increase rapidly, leading to increased bradykinin and nitric oxide and decreased pulmonary vascular resistance. Circulating prostaglandins, responsible for maintaining patency of the DA in utero, fall rapidly. – These changes in pressures lead to decreased flow across, and eventual closure of, the FO and DA. Functional closure of the FO is nearly immediate after birth, when the pressure change “pushes" the septum primum against the septum secundum. Fusion of the septa occurs within the first 3 months of life. Closure of the DA usually occurs within the first 3 to 10 days of life.

DISEASE/PATHOPHYSIOLOGY

• Intrauterine fetal hypoxia leads to a “diving reflex.” – Heart rate slows to decrease myocardial oxygen demand. – Blood is preferentially shunted to the brain, myocardium, and adrenals. – Transient hypertension results; however, as hypoxia persists, cardiac output and myocardial contractility fall, leading to hypotension. – These changes may lead to a depressed neonate, hypoxia in the neonatal period, and delayed transition (see below). • Changes in the pulmonary circulation in utero can lead to delayed or incomplete transition to a neonatal circulation. – Maternal NSAID use can cause closure of the DA in utero; this causes increased pulmonary blood flow and hypertrophy of the pulmonary vasculature. This hypertrophy can also be seen with post-term gestation and chronic placental insufficiency. – Congenital diaphragmatic hernia and pleural effusions lead to lung compression and decreased size of the pulmonary vascular bed. This can lead to pulmonary hypertension in the neonatal period. • Dysfunctional transition to extrauterine circulation (3): – Transient hypoxia is well-tolerated in the neonate. Prolonged hypoxia or acidosis, however, can lead to impaired transition from fetal to neonatal physiology. This disorder is called persistent fetal circulation or persistent pulmonary hypertension of the newborn (PPHN).

Continued hypoxia maintains in utero levels of pulmonary vasoconstriction due to a lack of bradykinin and NO production. High pulmonary vascular resistance leads to increased flow across the DA, mechanically maintaining its patency. High pulmonary artery pressures lead to high right heart pressures, which prevent functional closure of the FO. Hypoxia also leads to persistently elevated prostaglandin levels, further maintaining the patency of the DA. – PPHN, if untreated, can lead to persistent hypoxia, irreversible pulmonary hypertension, and right heart failure. – Treatment is aimed at correcting reversible causes of hypoxia and delivering supplemental oxygen if necessary.

PERIOPERATIVE RELEVANCE

• Maintenance of fetal circulation: Fetal circulation, specifically patency of the DA, can be maintained pharmacologically (with intravenous prostaglandin infusion), as a bridge to surgery for congenital heart disorders featuring obstruction to outflow of oxygenated blood. For example: – Aortic stenosis – Aortic atresia – Hypoplastic left heart syndrome – D-Transposition of the great arteries

GRAPHS/FIGURES

FIGURE 1. Fetal circulation. Numbers are percentage of combined left and right ventricular output reaching each point.

Ao—Ascending Aorta, PA—Pulmonary Artery, RV—Right Ventricle, LV—Left Ventricle, RA—Right Atrium, SVC—Superior Vena Cava, LA—Left Atrium, IVC—Inferior Vena Cava. (Adapted from Ostheimer GW. Anaesthetists’ role in neonatal

resuscitation and care of the newborn. Can J Anaesth. 1993;40:R50–R63, with permission.)

REFERENCE

1. Ostheimer GW. Anaesthetists’ role in neonatal resuscitation and care of the newborn. Can J Anaesth. 1993;40:R50–R63. 2. Lakshminrusimha S, Seinhorn RH. Pulmonary vascular biology during neonatal transition. Clin Perinatol. 1999;26:601–619. 3. Wimmer JE. Neonatal resuscitation. Pediatr Rev. 1994;15:255–265. See Also (Topic, Algorithm, Electronic Media Element) • Fetal heart tracings • Congenital diaphragmatic hernia • Tetralogy of Fallot

CLINICAL PEARLS

• Fetal circulation exists primarily as a series circuit with the RV as the main systemic ventricle and the LV mainly delivering blood to the brain and myocardium. This is possible through 3 main shunts: the DV, DA, and FO. • The neonate’s first breath causes an increase in oxygen tension and decreased pulmonary vascular resistance while umbilical cord clamping causes increased systemic vascular resistance. This leads to the functional closure of the DA and FO. • Delayed transition to neonatal circulation can be caused by persistent hypoxia and acidosis in the neonatal period or by structural anomalies in the heart or lungs, and can lead to a persistent fetal circulation or PPHN (with resultant persistent hypoxia and right heart failure). The mainstay in treatment of delayed transition is avoidance and correction of hypoxia and acidosis by mechanical ventilation and supplemental oxygen. • In certain congenital heart defects, patency of the DA can be maintained with prostaglandin infusion as a bridge to surgery.

FETAL HEART TONES Richard C. Month, MD

BASICS DESCRIPTION

• Electronic continuous fetal heart monitoring has become the mainstay of intrapartum management of fetal well-being. The technique utilizes both changes in fetal heart rate and timing of contractions to infer the intrapartum status of the neonate. • The team-oriented approach in caring for the obstetric patient makes it imperative that the anesthesia provider understands the terminology, appreciates the level of concern, and can effectively communicate the tracings. • Fetal heart rate (FHR) can be monitored externally by continuous Doppler ultrasound or internally by fetal scalp electrode. • Uterine contraction pattern can be monitored externally by tocodynamometry or internally by intrauterine pressure transducer. • A reassuring fetal heart rate tracing correlates more than 90% of the time with a 5-minute Apgar score of 8 or higher. However, a nonreassuring fetal heart rate tracing carries a falsepositive rate as high as 50% (1)[A].

PHYSIOLOGY PRINCIPLES

• Fetal heart rate pattern is the result of dynamic interplay between fetal sympathetic and parasympathetic nervous systems. • Fetal baroreceptors and chemoreceptors respond to asphyxia, acidosis, anemia, and/or infection. The activity of these peripheral and central receptors mediates parasympathetic and sympathetic tone, resulting in changes in the fetal heart tracing. • These patterns are discussed in terms of 4 separate and interrelated parameters: Baseline, variability, accelerations, and decelerations (2)[A]. – Baseline: – The mean fetal heart rate in any 10-minute window. – Normal is 110–160 beats per minute (BPM). – Variability: – Irregular fluctuations in both frequency and amplitude of fetal heart tracing measured over a 10-minute period. – Classified as absent (no fluctuation from baseline), minimal (<5 BPM from baseline), moderate (6–25 BPM from baseline), or marked (>25 BPM from baseline). – Moderate variability is considered normal. – Accelerations: – Visually apparent abrupt increases in fetal heart rate of at least 15 BPM lasting at least 15 seconds. – For fetuses less than 32 weeks of gestation, an increase of at least 10 BPM for at least 10 seconds is sufficient to be considered as an acceleration.

– Presence is generally considered reassuring; however, absence is not necessarily abnormal. – Decelerations: – Visually apparent, abrupt decreases in fetal heart rate of at least 15 BPM lasting at least 15 seconds. – Early deceleration: Gradual, symmetric decrease and return of fetal heart rate associated with uterine contraction; the nadir of the deceleration occurs simultaneous with the peak of the contraction (Figure 1).

FIGURE 1. Early deceleration. Gradual, symmetric decrease and return of FHR that occurs simultaneously with the peak of uterine contraction.

– Late deceleration: Gradual, symmetric decrease and return of fetal heart rate associated with uterine contraction; the nadir of the deceleration occurs after the peak of the contraction (Figure 2).

FIGURE 2. Late deceleration. Gradual, symmetrical decrease and return of FHR that occurs after the beginning of a uterine contraction.

– Variable deceleration: Abrupt, asymmetric decrease and return of the fetal heart rate. When associated with uterine contractions, the onset, nadir, and duration vary with successive contractions (Figure 3).

FIGURE 3. Variable deceleration. Abrupt, asymmetric decrease and return of FHR that lasts greater than 15 seconds and

less than 2 minutes.

DISEASE/PATHOPHYSIOLOGY

• Baseline – Fetal bradycardia is usually associated with fetal asphyxia and acidosis, especially when FHR was previously normal. In rare situations, fetal bradycardia is caused by maternal or fetal disease, including certain autoimmune disorders. – Fetal tachycardia is most commonly secondary to maternal infection and/or fever (e.g., chorioamnionitis). Other causes of tachycardia include fetal anemia, hypovolemia, or congenital heart disease. • Variability – Intact variability implies intact sympathetic and parasympathetic nervous systems and, by extension, an intact central nervous system. – Decreases in variability imply fetal CNS depression and can be caused by: Fetal asphyxia and acidosis Normal fetal sleep Maternal medications (beta blockers, opioids, anxiolytics, magnesium, lithium) Maternal general anesthesia • Accelerations – The presence of accelerations is a reassuring sign, further implying an intact CNS. – Lack of accelerations, however, is a nonspecific sign that, by itself, is neither reassuring nor nonreassuring. • Decelerations – Early decelerations are associated with fetal head compression within the birth canal. The resulting increased fetal intracranial pressure leads to reflex bradycardia. It is not considered worrisome and usually foretells imminent delivery. – Late decelerations are associated with uteroplacental insufficiency. Lack of sufficient oxygen transfer leads to fetal acidosis and hypoxia. Through chemoreceptor activation, heart rate slows to maximize oxygen extraction and decrease demand, and blood is shifted centrally to supply the most vital organs (brain, heart, adrenals). Always considered abnormal and a poor prognostic sign. – Variable decelerations are associated with umbilical cord compression. Compression of the umbilical artery removes the low-resistance placenta from the fetal circulation, causing an abrupt increase in fetal systemic vascular resistance. This activates fetal baroreceptors causing rapid reflex bradycardia. Can become worrisome if they are prolonged or repetitive due to worsening fetal oxygenation of acidosis. • Sinusoidal heart rate tracing – Specific pattern of fetal heart rate. Smooth sine-like waves with 3–5 cycles per minute lasting 20 minutes or longer. – Always considered profoundly abnormal. – Associated with chronic fetal anemia (e.g., Rh isoimmunization), fetal or fetal-maternal hemorrhage, or acute fetal asphyxia.

PERIOPERATIVE RELEVANCE

• There exists a 3-tiered FHR Classification System to aid in determining the presence of fetal acidemia or the need to intervene (2)[A]. • Category I fetal heart tracings are normal (reassuring) and are indicative of fetal well-being. It consists of all of the following: – Baseline FHR 110–160 BPM – Moderate variability – No late or variable decelerations. • Category II fetal heart tracings are of indeterminate significance. It consists of all tracings that do not fall into Category I or Category III. It should be reassessed frequently. • Category III fetal heart tracings are abnormal (nonreassuring) and are highly predictive of fetal acidosis. It should be met with prompt intervention including correction of maternal hypotension, oxygen therapy, maternal repositioning, etc. It may indicate the need for urgent/emergent delivery. It consists of either of the following: – Absent variability WITH recurrent late decelerations, OR recurrent variable decelerations, OR fetal bradycardia – Sinusoidal FHR pattern.

REFERENCES

1. Schifrin BS, Dame L. Fetal heart rate patterns. Prediction of Apgar score. JAMA. 1972;219: 1322–1325. 2. Macones GA, Hankins GD, Spong CY, et al. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: Update on definitions, interpretation, and research guidelines. Obstet Gynecol. 2008;112:661–666. 3. Graham EM, Peterson SM, Christo DK, et al. Intrapartum electronic fetal heart rate monitoring and the prevention of perinatal brain injury. Obstet Gynecol. 2006;108(3 Pt 1):656–666.

ADDITIONAL READING

• Perinatology.com. Intrapartum fetal heart rate monitoring. http://www.perinatology.com See Also (Topic, Algorithm, Electronic Media Element) • Fetal cardiovascular physiology • Uterine blood flow • Cesarean section, emergent

CLINICAL PEARLS

• Normal fetal heart tracing correlates highly with a 5-minute Apgar score of 8 or higher; however, an abnormal tracing can have a false-positive rate as high as 50%. • Tracings are described by 4 components: Baseline, variability, accelerations, and

decelerations. • Abnormal or absent variability can be associated with fetal CNS depression and/or fetal asphyxia. However, studies have not conclusively demonstrated its effect on perinatal mortality or pediatric neurologic morbidity (3). • Late decelerations are the result of uteroplacental insufficiency and indicate periods of fetal hypoxia. They are always abnormal. • Fetal heart tracings are now classified into 3 categories: Category I tracings are normal and indicative of fetal well-being, Category II tracings are indeterminate, and Category III tracings are abnormal and require intervention.

FIBRINOGEN

Kenichi A. Tanaka, MD, MSc Satoru Ogawa, MD

BASICS DESCRIPTION

• Fibrinogen, or Factor I, is converted to fibrin by thrombin and is a critical component of the coagulation system. • Perioperatively, hypofibrinogenemia may be treated with purified human fibrinogen, cryoprecipitate, or fresh frozen plasma. PHYSIOLOGY PRINCIPLES

• Normal plasma fibrinogen in adults is 1.5–3.5 g/L (150–350 mg/dL). Synthesis occurs in the liver and is increased during an inflammatory state (infection, pregnancy, etc.). • Physiological function: Fibrinogen is captured in the wound by activated platelets via glycoprotein IIb/IIIa receptors. A fibrin monomer is formed after thrombin cleaves peptides from fibrinogen. Thrombin also activates factor XIII, which cross-links fibrin monomers into a mesh. Fibrin can catalyze plasmin activation by serving as binding sites (lysine residues) for plasminogen and tissue plasminogen activator. • Purified human fibrinogen (lyophilized) is currently indicated for acute bleeding episodes in patients with congenital fibrinogen deficiency (e.g., afibrinogenemia, hypofibrinogenemia). – Derived from pooled human plasma – The concentrate is pasteurized (heat treated) at 60°C for 20 hours for virus inactivation. – Can be stored between +2 to +8°C for 30 months – Therapeutic target level is 1.0–1.5 g/L (or 100–150 mg/dL). – In patients with congenital hypofibrinogenemia, the half-life is reported to be 78.7 ± 18.1 hours. DISEASE/PATHOPHYSIOLOGY

• Factor I deficiency: Presents as a combined bleeding disorder; it affects both platelets and clotting – Qualitative: Dysfibrinogenemia results from defects to the factor I molecule. Patients rarely present with bleeding; in fact, some are predisposed to forming clots. Typically does not require any treatment such as cryoprecipitate, fresh frozen plasma, or purified fibrinogen. Occasionally, patients may be on anticoagulants. – Quantitative: Both conditions are inherited in an autosomal-dominant fashion and can affect both males and females. Afibrinogenemia is the complete absence of fibrinogen and is typically diagnosed in newborns. It often presents as bleeding from the umbilical cord, genitourinary tract, or CNS.

Hypofibrinogenemia is a low level of fibrinogen (<100 mg/dL). Symptoms can range from mild, moderate, to severe bleeding. • Increased fibrinogen levels: – Stroke: Associated with an increased risk of fatal and non-fatal, first-time, and hemorrhagic and ischemic strokes. – Coronary artery disease: Patients have increased levels, particularly those with a history of myocardial infarction. – Independent risk factor. Some studies have suggested that increased levels of fibrinogen exceed the effects of homocysteine, cholesterol, and other lipids in the pathogenesis of myocardial and cerebral infarction. – Mortality. A significant independent predictor of death from all causes in both men and women. This is believed to be due to its ability to promote thromboses, the underlying mechanisms for ischemia of myocardial infarction and stroke. – Cancer, diabetes, hypertension: Increased levels have been associated with these disease states. – Inflammatory process: Fibrin may play a role in inflammatory processes such as the development of rheumatoid arthritis. – Modification of levels. Smoking cessation, exercise, and medications have been shown to decrease levels. • Complications of fibrinogen replacement: – Purified fibrinogen: In disseminated intravascular coagulation (DIC), it can potentially worsen coagulopathy and organ dysfunction by forming fibrin in microcirculations. Allergic reactions The risks of pathogen transmission are considered to be low but possible for nonenveloped virus including parvovirus B19 and hepatitis A. Venous and arterial thromboembolic complications should be cautioned. The safety of purified human fibrinogen concentrate during pregnancy or breastfeeding has not been established in controlled clinical trials. • Complications of cryoprecipitate and fresh frozen plasma replacement: – Volume overload and decreased hematocrit – Transfusion-related acute lung injury – Thromboembolic risks with cryoprecipitate – Infectious transmission – Acute hemolytic transfusion reaction, nonhemolytic febrile, and allergic reactions – Hypocalcemia

PERIOPERATIVE RELEVANCE

• Measuring fibrinogen: – The Clauss method is used to measure the fibrinogen concentration (30–60 minutes turnaround time). It may be falsely elevated after large amounts of hydroxyethyl starch infusion. – Thromboelastometry can be used to measure fibrin(ogen)-specific clot firmness using cytochalasin D (FIBTEM value below 7 and 10 mm suggests plasma fibrinogen <150 mg/dL).

• “Acquired” hypofibrinogenemia: – Major bleeding can be accompanied by decreased levels during trauma and surgery. Assuming normal fibrinogen level at baseline, critical levels (1 g/L or 100 mg/dL) of fibrinogen are reached after a loss of about 1.4 times the blood volume. – Cell saver: Large amounts of shed blood processed in the cell salvage system can deplete plasma coagulation factors, including fibrinogen. – Disseminated DIC that is associated with severe sepsis and eclampsia. • Purified fibrinogen replacement: – No blood typing or thawing is necessary. – Less likely to induce hemodilution and thrombocytopenia after infusion compared to fresh frozen plasma (FFR). • Following major obstetric hemorrhage, a work up should include an assessment of fibrinogen levels. • Fibrin sealant: Human plasma-derived fibrinogen is clinically used as a fibrin sealant (Tisseel, Crosseal, Evicyl) for topical hemostasis. EQUATIONS

• Dose (mg/kg body wt) = [target level (mg/dL) – measured level (mg/L)]/1.7 (mg/dL per mg/kg body weight). • To raise plasma fibrinogen from 99 to 150 mg/dL, the required dose is (150 – 99)/1.7 = 30 mg/kg. • In case of bleeding and fibrinogen level is unknown, the recommended initial dose is 70 mg/kg. GRAPHS/FIGURES

See Table

REFERENCE

1. Manco-Johnson MJ, Dimichele D, Castaman G, et al. Pharmacokinetics and safety of fibrinogen concentrate. J Thromb Haemost. 2009;7:2064–2069. 2. Hiippala ST, Myllylä GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg. 1995;81:360–365. 3. Kruskal JB, Commerford PJ, Franks JJ, et al. Fibrin and fibrinogen-related antigens in patients with stable and unstable coronary artery disease. NEJM. 1987;317(22):1361– 1365. 4. Nienaber U, Innerhofer P, Westermann I, et al. The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion. Injury. 2011;42(7):697–701. 5. Alexopoulos D, Ambrose JA, Strump D, et al. Thrombosis-related markers in unstable angina pectoris. J Am Coll Cardiol. 1991;17(4):866–871. 6. Zhang B, Zhang W, Li X, et al. Admission markers predict lacunar and non-lacunar stroke in young patients. Thromb Res. 2011;128(1):14–17. 7. Bembenek J, Karlinski M, Kobayashi A, et al. Early stroke-related deep venous thrombosis:

Risk factors and influence on outcome. J Throm Thrombolysis. 2001;32(1):96–102. 8. Lowe G. Can haemostatic factors predict atherothrombosis? Intern Emerg Med. 2001;6(6):497–501. See Also (Topic, Algorithm, Electronic Media Element) • Fresh frozen plasma • Cryoprecipitate • Coronary artery disease • D-dimer • Transfusion related lung injury

CLINICAL PEARLS

• Fibrinogen replacement in congenital fibrinogen deficiency reduces bleeding episodes and thromboembolic complications related to invasive procedures. • Antifibrinolytics (-aminocaproic acid and tranexamic acid) may be useful in stabilizing fibrin against a premature breakdown by plasmin. It is not recommended in cases of DIC. • Coagulase-positive bacteria (e.g., Staphylococcus aureus) are able to convert fibrinogen to fibrin as a defense mechanism, enabling abscess formation. • Red blood cells can be split apart by fibrin strands as they flow through a forming clot. These fragmented RBCs are called schistocytes and can result in a microangiopathic hemolytic anemia. • In acute respiratory distress syndrome, neutrophils create capillary leakage that allows fibrinogen and proteins into the lung space and the creation of hyaline membranes. • Estrogen increases the synthesis of fibrinogen among other factors and inhibits antithrombin III. • D-dimer is a measure of fibrin split products and may be a useful laboratory measurement to rule out pulmonary embolism in low-risk patients. During fibrinolysis, activated plasmin degrades the cross-linked fibrin, which releases fibrin degradation products and exposes the D-dimer antigen, which is typically not present in the body except when the coagulation system has been activated.

FLOW VOLUME LOOPS Sylvia H. Wilson, MD Ilka Theruvath, MD, PhD

BASICS DESCRIPTION

• Spirometry measures lung volumes (y-axis) as a function of time (x-axis). – Flow rates are determined from spirometry by measuring volume achieved over a given time period (y/x values).

FIGURE 1. Spirometry and lung volumes.

• Flow volume loops are a graphic representation of inspiratory and expiratory air flow (yaxis) as a function of lung volume (x-axis). It measures a complete respiratory cycle in a clockwise manner from forced maximal expiration to maximal inspiration. – Components of maximum air flow depend on volumes.

FIGURE 2. Normal flow volume loop.

– Volume (x-axis): Movement along the x-axis from left to right indicates decreasing lung volumes. – Expiration (positive y-axis): Curve moves from high to low lung volumes (left to right on x-axis). There is a rapid rise to peak expiratory flow (PEF) followed by a linear fall as lung volumes decrease, airways narrow, and resistance increases. – Inspiration (negative y-axis): Curve moves from low to high lung volumes (right to left) in a symmetrical saddle shape.

PHYSIOLOGY PRINCIPLES

• Lung volumes (Figure 1): Measurements obtained with spirometry – Tidal volume (TV): Volume of air measured with passive ventilation. – Inspiratory reserve volume (IRV): Volume of air measured from end tidal volume inspiration to maximal inspiration. – Expiratory reserve volume (ERV): Volume of air measured from passive expiration to maximal forced expiration. – Residual volume (RV): Volume of air that remains in the lungs after maximal expiration; unable to measure with spirometry. • Lung capacities (Figure 1): Represents the sum of two or more lung volumes on spirometry. – Functional vital capacity (FVC): Volume of air forcibly exhaled after maximal inspiration (does not include RV). FVC = IRV + TV + ERV – Functional residual capacity (FRC): Volume of air present in the lungs at the end of passive expiration. FRC = ERV + RV – Total lung capacity (TLC): Volume of air contained within the lungs following maximal inspiratory effort. TLC = FVC + RV • Lung flows (Figure 2): – PEF: Maximum rate of respiratory gas flow during expiration (peak of expiratory curve). Following PEF, the slope of the expiratory curve is nearly linear. It is a function of airway diameter, patient effort, and expiratory muscle strength – Maximal expiratory flow at 50% FVC (MEF50): Flow value on the positive y-axis at the midpoint of the x-axis. – Maximal inspiratory flow at 50% FVC (MIF50): Flow value on the negative y-axis at the

midpoint of the x-axis. – Under normal conditions, MEF50 is only slightly less than MIF50 (secondary to dynamic

compression resulting in reduced flow). – Under pathophysiologic conditions, the discrepancy between the MEF50 and MIF50 can be

significant. • Comparison of flow-volume curves performed during resting ventilation with those during forced inspiration and expiration should demonstrate significant ventilatory reserves in normal subjects (1)[B].

DISEASE/PATHOPHYSIOLOGY

• Obstructive lung disease: – Asthma, chronic bronchitis, bronchiectasis, COPD

FIGURE 3. Obstructive lung disease.

– Curves shift leftward on the x-axis secondary to hyperinflation. “Air trapping” results in higher lung volumes and RV. – PEF and MEF50 are significantly reduced, and MEF50 < MIF50.

– “Scalloping” of the expiratory loop (positive y-axis) indicates reduced expiratory flow at all lung volumes (no longer linear). – Since inspiratory flow (not expiratory flow) is primarily increased during exercise, patients with obstructive disease experience increased end-expiratory lung volumes (hyperinflation) with exertion. This may be in addition to hyperinflation present at baseline. • Restrictive lung disease: – Fibrosis, scoliosis, obesity

FIGURE 4. Restrictive lung disease.

– Curves shift rightward on the x-axis secondary to a decreased TLC; all lungs volumes are reduced. – PEF, MEF50, and MIF50 are all reduced; flow reduction is congruent over the inspiratory and expiratory loops and MEF50 ∼ MIF50. Additionally, PEF is not as diminished or

affected compared to obstructive disease. • Fixed upper airway (extrathoracic) obstruction: – Tracheal stenosis, goiters

FIGURE 5. Fixed extrathoracic obstruction.

– Volumes (x-axis) are not affected. – Flow is decreased throughout the respiratory cycle at all lung volumes. – Curves are flattened on both the inspiratory and expiratory curves, MEF50 ∼ MIF50.

• Variable (nonfixed) upper airway (extrathoracic) obstruction:

– Vocal cord dysfunction, obstructive sleep apnea, tracheomalacia

FIGURE 6. Variable extrathoracic obstruction.

– Volumes (x-axis) are not affected. – Flow is decreased with inspiration but does not affect expiration (MEF50 > MIF50). PEF is

unchanged. – The inspiratory curve is flattened. – Insensitive test for upper airway obstruction: The tracheal lumen circumference must be decreased to less than 8 mm (80% reduction in tracheal area) before abnormalities are detected (2)[B]. • Variable (non-fixed) intrathoracic obstruction: – Endobronchial tumors or bronchial compression by other malignancies (anterior mediastinal masses)

FIGURE 7. Variable intrathoracic obstruction.

– Volumes (x-axis) are unchanged. – Flow is decreased during expiration but does not affect inspiration (MEF50 < MIF50); PEF is significantly reduced.

– The expiratory curve is markedly affected.

PERIOPERATIVE RELEVANCE

• Flow-volume loops can aid in the diagnosis and monitoring of the progression of chronic lung diseases. • Flow volume loops provide an alternative to advanced imaging modalities that are not immediately available or feasible in the operative room and intensive care unit. – Asthma, COPD exacerbations – Endobronchial intubations • Vocal cord dysfunction (Figure 6): Flow volume loops are commonly utilized to confirm the diagnosis (3)[B]. • Anterior mediastinal mass (Figure 7): In addition to the clinical history and radiological imaging, flow-volume loops provide a tool to measure the “functional” effects of a mass. Abnormalities in the expiratory loop may be accentuated in the supine position and may indicate the potential for complete airway obstruction with anesthetic induction and muscle relaxation.

EQUATIONS

• FVC = IRV + TV + ERV; where FVC is forced vital capacity, IRV is inspiratory reserve volume, TV is tidal volume, and ERV is expiratory reserve volume • FRC = ERV + RV; where FRC is functional residual capacity, ERV is expiratory reserve volume, and RV is residual volume • TLC = FVC + RV; where TLC is total lung capacity, FVC is forced vital capacity, and RV is residual volume

REFERENCE

1. Stoller JK. Spirometry: A key diagnostic test in pulmonary medicine. Cleve Clin J Med. 1992;59:75–78. 2. Dempsey JA, McKenzie DC, Haverkamp HC, et al. Update in the understanding of respiratory limitations to exercise performance in fit, active adults. Chest. 2008;134:613– 622. 3. Deckert J, Deckert L. Vocal cord dysfunction. Am Fam Physician. 2010;81:156–159.

ADDITIONAL READING

• Gal TJ. Pulmonary function testing. In Miller’s anesthesia, 6th ed., chap. 26. 2004:1100– 1103. • Stock MC. Respiratory function in anesthesia. In Barash PG, ed. Clinical anesthesia, 5th ed, 804–807. • Philadelphia, PA: Lippincott Williams & Wilkins, 2006.

See Also (Topic, Algorithm, Electronic Media Element) • Spirometry • Anterior mediastinal mass

• Asthma

CLINICAL PEARLS

• Spirometry is the measurement of volume (y-axis) versus time (x-axis). • Flow volume loops are plots of air flow (y-axis) as a function of lung volume (x-axis) during FVC maneuvers obtained by spirometry. All determinants of air flow depend on lung volumes. • PEF, maximal expiratory flow at 50% vital capacity (MEF50), and maximal inspiratory flow at 50% vital capacity (MIF50) are useful in describing dynamic airway obstruction. The volumes and shape of flow-volume loops provide additional information. • Flow-volume loops are instructive in the preoperative assessment (vocal cord dysfunction, anterior mediastinal mass, chronic lung disease) and intraoperative and postoperative evaluation (asthma exacerbation).

FRESH FROZEN PLASMA Kenichi A. Tanaka, MD, MSc Satoru Ogawa, MD

BASICS DESCRIPTION

• Transfusion of fresh frozen plasma (FFP) is mainly indicated for the treatment of complex coagulopathies in which multiple coagulation factors and inhibitors are depleted. Some common indications include the following (1,2): – Massive bleeding in trauma, cardiovascular surgery, or organ transplantation with prolonged prothrombin time and/or activated partial thromboplastin time – Active bleeding during or prior to invasive procedures/surgery in patients with congenital or acquired factor deficiency when no alternative therapies (factor concentrates) are available. – Acute reversal of vitamin K antagonist therapy – Disseminated intravascular coagulation – Thrombotic thrombocytopenia purpura • A cross matching is not required, but ABO compatibility should be considered before transfusion (Table 1). See Table PHYSIOLOGY PRINCIPLES

• Normal plasma volume is about 50 mL/kg or 3,500 mL in a 70-kg man. • Normal coagulation factor levels are in the range of 50–150% (0.5–1.5 IU/mL). • Plasma proteins exert an oncotic pressure of 25–30 mm Hg (60–70% derived from albumin). Normal plasma albumin levels are 3.5–5.0 g/dL. • Plasma preparation: – Whole blood centrifuge: Donor whole blood is centrifuged and the top plasma fluid layer is separated from red blood cells and platelets. – Plasmapheresis donations: Allows for a single donor and reduces recipient exposure to infection and HLA antibodies. It is an extracorporeal therapy technique that involves removal of whole blood, sequestration of plasma via a cell separator, and return of nonplasma components. • Freezing: – FFP is frozen within 8 hours of collection to –18°C to help prevent inactivation of labile coagulation factors V and VIII. – FP24 is the plasma that is frozen within 24 hours of phlebotomy (3). It is being used increasingly as a substitute for FFP because it allows for selection for male-only donors in an attempt to reduce the risk of transfusion-related acute lung injury (TRALI). It contains slightly lower levels of factors V and VIII, but their replacements are not typically indicated.

– Although they are technically different products, they are considered therapeutically equivalent. Both are stored, thawed, and infused similarly. • Storage: – <–18°C: products can be stored for up to 12 months – <–65°C: products can be stored up to 7 years • Contents: – 1 donor unit of FFP = 250 mL (∼220 mL plasma, ∼30 mL anticoagulant) – In theory, 1 mL of plasma = 1 unit of coagulation factors; thus 1 plasma unit contains 220 units. Actual coagulation factors vary significantly among different plasma units. Freezing and thawing may reduce factor levels. – Contains coagulation factors, anticoagulant proteins, albumin, and immunoglobulins – Devoid of red cells, leukocytes, and platelets. (The lack of leukocytes makes the risk of CMV transmission a nonissue.) • Thawed FFP – After thawing, FFP contains near normal levels of many plasma proteins (procoagulant and inhibitory components of the coagulation cascades, acute phase proteins, immunoglobulins, and albumin), fats, carbohydrates, and minerals in circulation. – Coagulation factors are reasonably well maintained with some decreases of factor V and VIII in thawed plasma kept at 1–6°C for up to 5 days. • ABO compatibility: – Antigenic red blood cells are removed during processing; however, small amounts may still be present in donor FFP. Additionally, ABO antigens may be present in the donor FFP. To that extent, although ABO compatibility is preferred whenever possible, in emergencies, it is not necessary. – Type AB is considered the universal FFP donor, as it has no antibodies in the plasma to Type A, B, AB or O erythrocytes (Table 1).

DISEASE/PATHOPHYSIOLOGY

• Complications of FFP administration: – TRALI is caused by anti-HLA antibodies present in donor plasma. It is the leading cause of morbidity and mortality after plasma transfusion. Female donor units are more likely to be associated with TRALI. In some countries, male donors are specifically chosen, with a demonstrated decrease in incidence. More commonly, male donor FP24 is being utilized. – Allergic reactions are the most common complication with a 1–3% incidence. – Patients with IgA deficiency may develop an anaphylactic reaction when transfused with IgA-containing blood products including FFP. IgA is a serum immunoglobulin and antibody found at mucosal surfaces. IgA deficiency results from an intrinsic B cell defect. – Fluid or circulatory overload can result from large volume administration, particularly in patients with limited cardiovascular reserve. • Infection transmission: – The risks of viral transmission, particularly hepatitis C and human immunodeficiency virus, have been significantly reduced by the nucleic acid testing of donor blood. – Treatment of FFP with methylene blue or solvent-detergent further reduces virus transmission risks. – Prion disease transmission (Creutzfeldt-Jakob disease) should be reduced by avoiding

plasma collections from an endemic area. – Hypocalcemia from citrate overload can occur with massive plasma transfusion.

PERIOPERATIVE RELEVANCE

• In adults, 1 unit of plasma increases most factors by ∼2.5%; 4 plasma units by ∼10%. A 10% increase in factor levels is typically necessary to make a significant change in coagulation status. However, this will vary depending on the patient’s size and clotting factor levels. • Pediatric dosing: 10–15 mL/kg gives a 15–20% rise in factor levels. • Little evidence exists to inform the best therapeutic plasma transfusion practice. Current indications include the following (2,3): – Abnormal coagulation screening tests in the face of bleeding or prophylactically in nonbleeding subjects prior to invasive procedures or surgery. – Microvascular bleeding in the presence of PT or PTT > 1.5 times normal. This is believed to correspond to factor levels <30% of normal. However, the relationship among coagulation tests, the extent of coagulopathy, and the need for FFP remains unclear. – Urgent reversal of warfarin; consider vitamin K if time permits and prothrombin complex concentrate if available. – Massive transfusion may require coagulation factor replacement with FFP without waiting for laboratory results. Abnormalities of PT/PTT are often seen after a rapid infusion >4 units of packed RBCs. The main advantage of “damage control resuscitation” with a fixed ratio (1:1) transfusion of RBC and FFP is the prevention of severe dilution and early correction of coagulopathy. – Isolated factor deficiency (factors II, V, VII, IX, X, XI) replacement II, V, VII, IX, X, XI) when specific component therapy is unavailable – Hereditary antithrombin or protein C deficiency; however, purified lyophilized antithrombin or protein C concentrate is available and preferable to FFP. – Disseminated intravascular coagulation – Plasmapheresis for thrombotic thrombocytopenic purpura – Infants with protein-losing enteropathy – Cell salvage processing can result in depletion of plasma fractions. FFP may be needed after several units have been administered • Plasma is not as viscous as packed RBCs and does not need to be diluted with crystalloid.

REFERENCES

1. Stanworth S, Brunskill SJ, Hyde CJ, et al. Appraisal of the evidence for the clinical use of FFP and plasma fractions. Best Pract Res Clin Hematol. 2006;19:67–82. 2. ’Shaughnessy DF, Atterbury C, Bolton Maggs P, et al. Guidelines for the use of fresh-frozen plasma, cryoprecipitate, and cryosupernatant. Br J Haematol. 2004;126:11–28. 3. Yim R. Fresh frozen plasma for transfusion: A review. Blood Bulletin. 2008;10:1–2. See Also (Topic, Algorithm, Electronic Media Element) • Transfusion-related lung injury • Red blood cell transfusion

• Infectious risk of transfusion

CLINICAL PEARLS

• Critical levels (20–25%) of normal coagulation factors levels are reached after a loss of twice the blood volume. • Excessive crystalloid/colloid administration in a massive hemorrhage can result in dilutional coagulopathy, which may be prevented by early administration of FFP. • Adult dosing, in general, is recommended with 5–8 mL/kg. However, a dose up to 10–30 mL/kg may be necessary to keep coagulation factors above 50% of normal. • Plasma-derived, virus-inactivated prothrombin complex concentrate is an alternative to FFP in acute reversal of vitamin K antagonist therapy. • Fresh frozen plasma administration is contraindicated for the augmentation of plasma volume or albumin concentration due to its potential for immunological and infectious risks as well as limited supply.

FUNCTIONAL RESIDUAL CAPACITY Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Functional residual capacity (FRC): – Is equal to residual volume (RV) plus expiratory reserve volume (ERV) – Is the volume of air in the lungs at the end of a normal exhalation or tidal volume (TV) – Participates in alveolar gas exchange, not volume movement. TV serves as the functional component of volume movement and gas exchange (“checking account" where most of the activity takes place). Gas (oxygen, volatiles, nitrogen) from the TV readily diffuses into the alveolar units that comprise the FRC (akin to a "volume of distribution"). – Functions as a “storage" or “reservoir" for O2 in the event of hypoxia or apnea ("overdraft coverage"). – Corresponds to an intrapleural pressure of 0 cm H2O. The outward rib cage expansion and

inward lung recoil forces are balanced (“tug-of-war" tie). • Factors that reduce FRC include: Compression of the thoracic wall, cephalad movement of abdominal contents and diaphragm, and increased blood volume of the chest/abdomen.

FIGURE 1. Lung volumes. FRC is the sum of ERV and RV. IRV = inspiratory reserve volume, FRC = functional residual capacity, VC = vital capacity, VT = tidal volume, ERV = expiratory reserve volume, RV = residual volume.

PHYSIOLOGY PRINCIPLES

• FRC is comprised of the RV and ERV. Lung capacities are comprised of lung “volumes." The lung volumes are measured parameters. FRC is approximately 35 mL/kg (~2,500 mL in a healthy 70–kg male). • The (inward) lung recoil force is referred to as transpulmonary pressure (Ptp). The (outward) chest wall force is referred to as the transmural pressure (Ptm). At end expiration of a

normal TV, Ptp and Ptm are numerically equal but opposite in sign (positive and negative),

resulting in an equilibrium. • FRC during a normal TV does not contribute to the minute ventilation (volume movement).

The open alveoli in the FRC, however, will equilibrate with the gas composition in the TV. Thus, FRC functions as a reservoir, or a volume of distribution, in which O2, nitrogen,

volatiles, and CO2 diffuse to. Assuming normal blood perfusion to the alveolar units,

oxygenation, ventilation, and gas exchange with the blood take place. During periods of apnea (no new oxygen in the TV), FRC becomes a valuable supply for oxygen. Hence, it provides “overdraft coverage” and buffers alveolar gas tensions against abrupt alterations in O2 and CO2 during the respiratory cycle.

– ERV during a forced vital capacity (FVC) can participate in volume exchange (open alveoli can contribute to gas exchange). – RV during a FVC cannot contribute to volume exchange (unable to empty the alveoli from dynamic airway closure/collapse). • The concept of FRC as a “reservoir” or “savings account” is utilized and harnessed when we preoxygenate prior to anesthetic induction. In the event of apnea, the body will have 35 mL/kg of 100% O2 available (e.g., a 70-kg healthy male: 35 mL × 70 kg 2,500 mL × 1.0 FiO2 = 2,500 mL O2; body uses ∼ 250 mL O2/minute). This provides additional time

before desaturation in the event that ventilation, laryngoscopy, or fiberoptic bronchoscopy are difficult or prolonged. • Alveoli within the FRC need to be patent/open in order for gas to diffuse into, participate in gas exchange, and function as an oxygen reservoir. Obstruction at any point during the breathing cycle or atelectasis may lead to a venous admixture. • In young healthy individuals, the majority of the alveoli in the FRC (RV + ERV) remain open in the standing position (available for gas exchange and reservoir). This is because the closing volume (CV) is less than FRC (CV <<< FRC). – Closing volume is the volume at which dynamic compression of the airways begins. – Alveoli do not have cartilaginous structures that hold them open but are instead dependent upon proteins (elastin, collagen, trypsin) that surround the alveoli in the parenchyma.

FIGURE 2. The proteins maintain a tight conformational structure that “pull" open the surrounding alveoli (tight coiling effect in parenchyma pulls open the alveoli which are essentially potential spaces).

– When lung volumes reduce (forceful exhalations, FVC, or reductions in FRC), Ptm is increased. When the volume falls below the CV, Ptm exceeds the ability of the

parenchymal proteins to keep alveoli open. Atelectasis and air trapping or auto-PEEP occurs.

– Alveoli in Zone 4 (lung bases) are most affected during maximal exhalation. They have low resting volumes from gravitational forces on blood (increased Ptm) and are vulnerable

to compression during active expiration. – CV is affected by age, smoking, and disease states that affect the tight conformational structure of these parenchymal proteins (reduced coiling). Thus, there is reduced alveolar patency and increased closing at all lung volumes; gas exchange cannot occur and shunting occurs. CV initially infringes upon ERV and proceeds into the TV. – Closing capacity (CC) = CV +RV • FRC is variable. Factors that affect the Ptp and Ptm can increase or reduce FRC. They include

the thoracic wall, abdominal wall, diaphragm, and blood volume within the lung/abdominal cavities. Meanwhile, CV is not variable but based upon the “health” or “tightness” of the surrounding parenchymal proteins. • FRC cannot be measured with spirometry; RV cannot contribute to volume exchange during a FVC and hence, cannot be directly measured – Gas dilution techniques: Inhalation of a known concentration and volume of an inert tracer gas, such as helium, is performed for 7–10 minutes in a closed circuit (allows for equilibration). The final exhaled helium concentration is diluted in proportion to the unknown volume of air in the patient’s chest (RV) and can be calculated. – The nitrogen-washout technique (single-breath and multiple-breath techniques): In the single-breath technique, the patient inhales 100% oxygen and exhales into a 1-way valve with a nitrogen sampler; creates a curve of nitrogen versus expired volume. At the beginning of exhalation, nitrogen concentration is 0 (dead space contribution that does not participate in alveolar exchange). With continued exhalation, nitrogen concentration starts increasing as alveolar volume is exhaled. – Bedside ventilator-based FRC measurement techniques are available. There is evidence that FRC measurement (combined with arterial oxygenation and respiratory compliance) can help guide and assess therapy.

ANATOMY

• Lung units: Alveoli, pulmonary capillaries. • Rib cage: Intercostal, sternocleidomastoid, and scalene muscles; xiphoid process, ribs. • Abdominal contents: Fat, fluid, blood flow, pregnancy. • Diaphragm: C3, C4, C5 bilateral innervations (affected with interscalene blocks).

DISEASE/PATHOPHYSIOLOGY

• Factors that reduce lung expansion will reduce FRC and result in alveolar collapse/atelectasis and air trapping. Atelectasis results in V/Q mismatch (shunting; blood perfuses collapsed alveoli and are not oxygenated; gas exchange cannot occur). With increased numbers of alveolar units being shunted, the F(A-a) gradient increases and hypoxia results. Furthermore, airway compliance, O2 reservoirs, and mixed venous O2 reduce; peak and static airway pressures increase. • Absorption atelectasis: Reductions in FRC also result in air trapping. Absorption of gas behind the closed or intermittently closed airway leads to collapse/atelectasis [hence V/Q mismatch, shunting, and increased F(A-a) gradient]. This may be exacerbated by a high

FiO2 from near complete uptake of oxygen in the alveoli. Room air and partial air mixtures

contain nitrogen which is inert and poorly dissolved in blood. As a result, nitrogen serves as an alveolar “filler,” reducing complete collapse (like foam packaging in a box; if compressed, less likely to be completely collapsed). • The outward chest wall force (Ptp) and inward lung recoil (Ptm) determine the FRC (intrinsic

factors). However, they are altered by factors that affect the thoracic wall, abdominal wall, diaphragm, and blood volume. These factors are variable, extrinsic, and often affected by anesthesia and surgery. FRC is still the volume at the end of a normal TV, and Ptp + Ptm

continues to equal 0 mm Hg; however, lung volume at FRC will be re-established • Thoracic wall: Reduction in diameter and cross-sectional area are seen with restrictive lung diseases affecting the chest wall—scoliosis, muscle dystrophies (ALS, paraplegia, etc.), and obesity (fat on the chest). – Age affects chest wall compliance. Babies have very compliant thorax and lung (allows for easy passage through birthing canal); FRC is small and roughly equal to RV. They also have a low O2 reservoir and increased O2 consumption (∼ 6 mL O2/kg/minute, double that of older children and adults) that results in rapid desaturation during apnea (1). – Elderly have ossified thoraxes that become stiffer and increase outward forces and FRC (3% per decade). CV, however, increases at a greater rate, leading to airway closure, atelectasis, and V/Q shunting. – Inspiratory muscle tone affects the intercostals, sternocleidomastoid, and scalene muscles during GA and/or NMBD (reduces thoracic outward force, FRC) (2). – Barrel chest, seen with emphysema, increases chest wall diameter, Ptm, TLC, and hence

FRC. It is a compensatory mechanism to reduce atelectasis in the face of an increased CV from damaged parenchymal proteins that are unable to maintain patent alveoli. • Abdominal wall: Obesity, pregnancy, ascites, abdominal and thoracic surgery, abdominal retractors and packing, pneumoperitoneum, and supine and Trendelenburg position allow for cephalad movement of abdominal contents. This results in external compression or “invasion” into the lung cavity and an increase in Ptp (reduces FRC).

• Diaphragm: Intrinsic muscle tone is reduced with NMBD and anesthesia (IV and volatile), reducing diaphragmatic excursion and lung expansion (reduced FRC). Bilateral diaphragm paralysis (cervical quadriplegia, surgical injury, radiation) produces similar effects on FRC. • Blood volume within lung/abdominal cavities as seen during surgery, congestive heart failure (CHF), acute respiratory distress syndrome (ARDS), and fluid overload states reduce lung expansion and hence FRC. • CV, unlike FRC, has limited variability. • An abnormal increase in FRC can result from obstructive airway diseases (asthma, reactive airway disease, emphysema, chronic bronchitis) due to an increase in RV, at the expense of ERV. The increased RV cannot contribute to the exhaled volume; gas exchange can occur in alveoli that open with inhalation/increased lung volumes, despite closing with exhalation (decreased lung volumes). – High-altitude inhabitants compensate for low atmospheric O2 with increased FRC and lung volumes in general. In this scenario, they increase the FRC compared to CV so that more

alveoli are open and can function in oxygen exchange. They have an increased work of breathing at the higher lung volumes. • Intraoperative shunt is greater in patients with pre-existing low PaO2, but the percentage increase is larger in healthy subjects

PERIOPERATIVE RELEVANCE

• Reductions in FRC may be significant intraoperatively and perioperatively. Intraoperative shunt is greater in patients with pre-existing low PaO2, but the overall percentage is larger

in healthy subjects. • Supine position (0.8 L) and induction of general anesthesia (0.5 L) are not inconsequential (1.3 L reduction; reduces lung volumes from 3.5 to 2.2 L, brings closer to, and may overlap CV) (1) • Although positive pressure ventilation reduces the effects of the diaphragm and abdominal wall on FRC, it does not negate it entirely (3). – Implementing large TV (10–12 mL/kg) and PEEP may increase FRC and gas exchange. Opens atelectatic alveoli during inspiration (allows O2 and CO2 to be exchanged with

blood); consider pressure control ventilation or an increased inspiratory pause time (increases time that alveoli are open during inspiration). – PEEP preferentially affects upper lung zones; airway closure and reduced FRC predominantly affect dependent lung zones. Higher PEEPs may improve airway patency in dependent lung regions but can reduce cardiac output and pulmonary perfusion (V/Q mismatching, dead space) • 30° head-up tilt (not back up) allows gravity to bring the abdominal contents downward, increase FRC, and reduce atelectatic units. • High FiO2 that is often used perioperatively can result in absorption atelectasis in poorly ventilated or “closed" alveoli. • After intubation, early recruitment maneuvers (up to 40 cm H2O for 10 seconds) may reduce

atelectasis. • Coughing during intubation, intraoperatively, or extubation reduces FRC. Avoid with adequate induction and NMB medication dosage and time for onset. Consider recruitment maneuvers prior to extubation. • Postoperative reductions in FRC can cause hypoxemia, atelectasis, and pneumonia; different etiology than intraoperative decreases. Results from absorption atelectasis (high O2 behind

closed airways), incisional pain, and reflex dysfunction of the diaphragm (local irritation, bowel distension, pneumoperitoneum) after abdominal and thoracic surgeries – Active lung expansion: Deep breathing exercise and coughing, incentive spirometry, CPAP. Intensity and frequency of sessions are more important than form of therapy. • Postoperative analgesia: Epidural analgesia may allow for deep breathing and diaphragmatic excursion.

EQUATIONS

• FRC = RV + ERV; FRC = TLC – IRV – TV; where FRC is functional residual capacity, RV is residual volume, ERV is expiratory reserve volume, TLC is total lung capacity, IRV is

inspiratory reserve volume, and TV is tidal volume. • CC = CV + RV; where CC is closing capacity, CV is closing volume, and RV is residual volume.

REFERENCES

1. on HF, Wahba WM, Craig DB. Airway closure, gas trapping, and the functional residual capacity during anesthesia. Anesthesiology. 1972;36(6):533–539. 2. Laws AK. Effects of induction on anaesthesia and muscle paralysis on functional residual capacity in the lungs. Can Anaesth Soc J. 1968;15(4):325–331.

3. Heinze H, Sedemund-Adib B, Heringlake M, et al. Changes in functional residual capacity during weaning from mechanical ventilation: A pilot study. Anesth Analg. 2009;108(3):911–915.

ADDITIONAL READING

• Murray and Nadel’s Textbook of Respiratory Medicine, 5th ed. Saunders, 2010.

See Also (Topic, Algorithm, Electronic Media Element) • Closing capacity • Spirometry • Ventilation and perfusion matching

CLINICAL PEARLS

• Functional residual capacity is comprised of the RV and ERV. • FRC is affected by several perioperative factors (general anesthesia, supine positioning, abdominal procedures, obesity, abdominal surgery, etc.) and can result in shunting.

GASTRECTOMY

Allen Alexander Holmes, MD, MS

BASICS DESCRIPTION General

• Gastrectomy describes the surgical excision of part (subtotal) or all (total) of the stomach. The most common indication is for cancer, but emergent cases of gastric trauma or uncontrollable bleeding ulcers do occur. Most bariatric procedures involve a functional subtotal gastrectomy. • Following incision, dissection involves separating the ligaments that connect the stomach to the spleen and colon. A clamp is placed at the duodenum, which is then resected and sutured close. Subsequently, the stomach is clamped and resected (partially or completely). The anastomosis is performed usually via a Roux-en-Y jejunal limb. – Esophagojejunostomy for total gastrectomy – Gastrojejunostomy for subtotal gastrectomy • For cancer, an associated limited “D1” or extensive “D2” lymphadenectomy is performed. • A feeding jejunostomy tube (J-tube) is frequently placed for postoperative nutrition. • Laparoscopy. Diagnostic evaluation may be performed prior to laparotomy. Resection may also be performed but has been limited to patients requiring a distal gastrectomy (early stage disease or palliation). Position

• Supine • Prep from nipples to pubis

Incision

• Midline laparotomy +/– lateral extension (“L” or Makuuchi incision) or bilateral subcostal incision (Chevron incision) • Laparoscopy via 3–5 small incisions for trochar insertion

Approximate Time

3–6 hours depending on the degree of lymphadenectomy and whether the anastomosis is hand-sewn versus stapled EBL Expected

• 100–200 mL for uncomplicated cases • Higher with extended lymphadenectomy (especially involving the spleen or pancreas) and total gastrectomy • Bleeding ulcers or traumatic injuries can result in massive blood loss

Hospital Stay

7–14 days, primarily dependent on tolerance of oral feeding Special Equipment for Surgery

Possible laparoscopic equipment EPIDEMIOLOGY Prevalence

In the US, there were 21,000 new cases of gastric cancer diagnosed in 2010. Prevalence

• Helicobacter pylori infection is implicated in distal gastric cancer • Gastric cancer patients have a mean age in their 70s

Morbidity

• Complication rate of 9% in subtotal gastrectomy and 13% for total gastrectomy • Postoperative complications are increased if lymph node dissection is performed; they are doubled if spleen or adjacent organs are removed.

Mortality

• In the US in 2010, there were 10,570 deaths due to gastric cancer. Increased occurrence in Japan, Iceland, Chile, and Australia. • Perioperative mortality is 1% in subtotal gastrectomy and 2% for total gastrectomy.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Avoid excessive fluid administration; a positive fluid balance may affect postoperative complications and mortality (particularly cardiac and pulmonary). • If a total laparoscopic approach is attempted, there is a possibility to convert to an open procedure. If a laparoscopic diagnostic exam is performed first, the case could be aborted on short notice. • An epidural catheter should be considered for adequate postoperative pain management.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Often asymptomatic • Vague pain, nausea, indigestion, early satiety, and weight loss • Melena for bleeding ulcers, leiomyosarcomas, and large adenocarcinomas

History

• Assessment of comorbidities • Bowel prep for surgery • Consumption of smoked, pickled, or salt-cured foods

Signs/Physical Exam • Usually nonspecific

• Rarely, a palpable epigastric mass

MEDICATIONS

• Gastric cancer patients demonstrate improved survival with chemotherapy prior to surgery (1). However, treatment can affect multiple organ systems: • Myelosuppression • 5-FU – Coronary vasospasm • Anthracyclines – Cardiac toxicity • Cisplatin – Nephrotoxicity • Trastuzumab – Cardiac toxicity and pulmonary toxicity • Ulcers. Acid reducing drugs including antacids, H2 blockers, and proton pump inhibitors

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC to evaluate bone marrow function • Chemistry panel (electrolyte derangements after bowel prep) • PT/PTT prior to epidural, especially in setting of recent chemotherapy • Staging CT or PET scan • Endoscopic exam

CONCOMITANT ORGAN DYSFUNCTION

• Malignancy. Types: • Adenocarcinoma (90–95%) • Lymphoma • Leiomyosarcoma • GI stromal tumor • Carcinoid • Usual comorbidities of advanced age • Ulcers refractory to medical therapy may be complicated by bleeding, perforation, or pyloric obstruction.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines can be titrated for anxiety • GI medications to decrease gastric volume and acid may be considered in patients at risk for aspiration. • Octreotide helps to minimize vasoactive compound release from carcinoid tumors • Deep venous thrombosis (DVT) prophylaxis should be discussed with the surgeon.

Special Concerns for Informed Consent

Epidural catheter placement, including risks and benefits, should be discussed if planned.

Antibiotics/Common Organisms

• Bowel anaerobes (Bacteroides, etc.) • 2nd or 3rd generation cephalosporin (cefotetan, cefoxitin, ceftriaxone) • Ertapenem (advantage of one time dose for 24-hour coverage) • Quinolone + metronidazole for β-lactam allergy

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with endotracheal tube • Epidural catheter for postoperative pain (mid-thoracic level) management

Monitors

• Standard ASA monitors • Arterial line for most cases to allow for beat-to-beat BP monitoring and frequent labs • Central venous access if large bore peripheral access is unavailable • Noninvasive hemodynamic monitors may be helpful in avoiding excessive fluid administration.

Induction/Airway Management

Generally, a rapid sequence induction is indicated as patients can have poor gastric emptying. Maintenance

• Volatile or IV balanced technique • Muscle relaxation is usually needed to assist with surgical exposure. • Narcotic or continuous epidural for pain management. Epidural infusions may be started intraoperatively; however, the sympatholysis may compound hypovolemia/hemorrhage; some practitioners wait until the period of blood loss has been completed to avoid this. • Fluids. Administration should be tailored to maintain an effective circulatory volume while avoiding interstitial fluid overload.

Extubation/Emergence

• A fully awake extubation is recommended to decrease the risk of aspiration. • Carefully secure and protect any NG tube if present as it will be impossible to replace across anastomosis without reopening.

POSTOPERATIVE CARE BED ACUITY

• A monitored bed (telemetry versus ICU) is typical for total gastrectomy or any case involving significant blood loss. • A regular floor bed is possible for uncomplicated subtotal gastrectomy in otherwise healthy patients.

ANALGESIA

• Epidural or PCA. In addition to providing improved pain relief in the first 72 hours after

surgery (2), epidural infusions are also associated with a decreased incidence of pulmonary complications (3). DVT prophylaxis should be considered when planning catheter removal. • Continuous bilateral transversus abdominis plane (TAP) blocks are an opioid-sparing alternative to epidurals, although evidence is lacking (4).

COMPLICATIONS

• Anastomotic leak or failure • Postoperative bleeding • Any cancer patient is at increased risk of DVT and PE. • Postoperative pneumonia • Poor oral feeding tolerance • Dumping syndrome – Result of poorly digested contents being dumped into small bowel. Symptoms include cramps and nausea and can be immediate or delayed in onset.

PROGNOSIS

5-year survival for gastric cancer is 30–50% for stage II and 10–25% for stage III

REFERENCES

1. agner AD, Unverzagt S, Grothe W, et al. Chemotherapy for advanced gastriccancer. Cochrane Database Syst Rev. 2010;(3):CD004064. [A] 2. erawatganon T, Charuluxanun S. Patientcontrolled intravenous opioid analgesia versus continuous epidural analgesia for pain after intra-abdominal surgery. Cochrane Database Syst Rev. 2005;(1):CD004088.[A] 3. Popping DM, Elia N, Marret E, et al. Protective effects of epidural analgesiaon pulmonary complications after abdominal and thoracic surgery: A meta-analysis. ArchSurg. 2008;143(10):990–999; discussion 1000. [A] 4. Charlton S, Cyna AM, Middleton P, et al. Perioperative transversus abdominis plane (TAP) blocks for analgesia after abdominal surgery. CochraneDatabase Syst Rev. 2010;12:CD007705. [B] See Also (Topic, Algorithm, Electronic Media Element) • Laparoscopy • Insensible fluid losses

CLINICAL PEARLS

• Communicate with the surgeon regarding the status of all NG tubes including esophageal stethoscopes and thermometers prior to stapling. • Compression of the right heart and concomitant hypotension is common as surgeons work at the distal esophagus. • Recent chemotherapy can cause multiorgan system derangements.

GASTROESOPHAGEAL REFLUX DISEASE (GERD) Tara L. Paulose, MD

BASICS DESCRIPTION

• Gastroesophageal reflux disease (GERD) describes the abnormal reflux of gastric contents into the esophagus due to – Incompetent or relaxed lower esophageal sphincter (LES) tone – Increased intragastric pressures • This can result in pulmonary aspiration during general anesthesia or sedation

EPIDEMIOLOGY Incidence

• Documented gastric reflux in 20–40% of the population

Prevalence

No predilection for age or sex Morbidity

• Discomfort • Can lead to metaplasia (Barrett’s), low-grade dysplasia, high-grade dysplasia, and ultimately adenocarcinoma. • Barrett’s metaplasia increases the risk of adenocarcinoma by 30–60 times that of the general population. Mortality

Esophageal cancer is the 7th leading cause of cancer death worldwide; information is not available on the number that results specifically from GERD. ETIOLOGY/RISK FACTORS

• Pregnancy • Obesity • Delayed gastric emptying; diabetes, history of vagotomy • Presence of a hiatal hernia • Presence of intra-abdominal pathology; tumor • Ingestion of offending foods and/or medications: – Caffeine – Alcohol – Calcium channel blockers – Nitrates – Beta-blockers

– Progesterone hormone

PATHOPHYSIOLOGY

• Reflux of acidic stomach contents into the esophagus is pathological and can result from factors that increase the barrier pressure; barrier pressure = intragastric pressure – lower esophageal pressure. It can result from an – Increased intragastric pressure – Incompetent LES – Excessive relaxation of the LES • Repeat and chronic exposure to acidic contents can result in atypical cell development and potentially adenocarcinoma of the esophagus.

Geriatric Considerations

The geriatric population often presents with atypical symptoms such as “anginal” pain and develop esophagitis secondary to concomitant use of medications (e.g. NSAIDs) to treat comorbid conditions. Pediatric Considerations

Common in the pediatric population, particularly in the first year of life, characterized as the complete absence of severely diminished LES tone. Pregnancy Considerations

This patient population carries an especially high-risk given the increase in abdominal pressure secondary to uterine enlargement as well as the effects of progesterone of the LES. ANESTHETIC GOALS/GUIDING PRINCIPLES

• GERD can result in the passive reflux and aspiration of stomach contents into the lungs during any anesthetic period where protective airway reflexes are blunted (including sedation). • Preoperatively, aim to neutralize and decrease the volume of gastric contents in order to minimize the possibility of reflux and thereby, aspiration. • Aim to minimize the risk of aspiration: Consider rapid sequence induction (RSI), avoid insufflating the stomach during hand ventilation, and consider endotracheal devices over supraglottic airways.

PREOPERATIVE ASSESSMENT SYMPTOMS

• “Heartburn;” anginal symptoms in the absence of cardiac findings • Regurgitation of actual gastric contents • Metallic taste in mouth • “Full” sensation in chest • Cough • Dysphagia • Hoarseness of voice

History

• Focused questions regarding presence, frequency, and severity • Exacerbation of symptoms while recumbent or bent over • Presence of symptoms with an empty stomach • History of sleeping with several pillows in the absence of cardiac history • Confirmation of NPO status • Review of comorbid conditions/factors that increase reflux/aspiration risk (e.g., diabetes, hiatal hernia, ileus, protracted hospital stay, opioid use) Signs/Physical Exam

• Typically unremarkable • Dental erosion • Wheezing; an uncommon finding

TREATMENT HISTORY

• Lifestyle modifications: – Weight loss – Avoidance of trigger foods/medications – Time lapse between oral intake and recumbency – Smaller, frequent meals – Elevation of head of bed • Nissen fundoplication is a surgical intervention that may be performed for persistent symptoms despite adequate treatment trials MEDICATIONS

• Antacids can immediately neutralize/increase the pH of gastric contents. Antacids are inorganic salts that release anions upon dissolving in acidic gastric secretions; anions combine and neutralize hydrochloric acid. Increasing the gastric fluid pH will inactivate pepsin, which then has bile-chelating effects as well as stimulates gastrin release; this results in enhanced motility and esophageal sphincter tone. Nonparticulates (sodium citrate, 0.3M) are more commonly used because mixing is more complete and rapid than particulate antacids and if aspirated, they cause less foreign body reactions. Chronic use can cause urine alkalinization and result in urolithiasis. • H2 receptor antagonists decrease the baseline parietal cell acid and volume secretion as well as blunt the response to normal stimulus (e.g., food, histamine, insulin, caffeine). It is a competitive antagonist of histamine and inverse agonist at H2 receptors of gastric parietal cells. In turn, the reduced acid and volume inactivates pepsin and stimulates gastric release. Chronic use can inhibit p450 enzymes and prolong the duration and concentration of warfarin, lidocaine, and diazepam. • Proton pump inhibitors irreversibly bind to and inhibit H+/K+ ATPase enzymes on parietal cells; they inhibit the “proton pump” and gastric acidity. This is the terminal step of gastric acid production and is irreversible; therefore, it is capable of inhibiting close to 100% of gastric acid secretion (1)[B].

DIAGNOSTIC TESTS & INTERPRETATION

Labs/Studies

• Largely a symptom-based diagnosis • Patients may have undergone an endoscopy, 24-hour esophageal pH monitoring, esophageal manometry, chest radiograph/upper GI series, or gastric emptying study on an outpatient basis. These tests are not typically ordered preoperatively. • EKG or cardiac enzymes may have been ordered to rule out cardiac etiology.

CONCOMITANT ORGAN DYSFUNCTION

• Esophagitis leading to Barrett’s esophagus • Increased risk of esophageal adenocarcinoma

CIRCUMSTANCES TO DELAY/ CONDITIONS

Generally speaking, there is no need to delay a case if appropriate airway technique and induction is undertaken by an experienced operator.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Antacids. Useful in urgent and emergent cases where immediate gastric acid reduction is desired (e.g., Cesarean sections); ideally administered 15–20 minutes prior to induction. Sodium citrate for adults: 10–30 mL PO q6h prn; pediatrics: 5–15 mL PO q6h. Can increase gastric fluid volume with resultant stomach distention; this can possibly increase nausea, emesis, and volume of aspirate should aspiration occur (can offset the desirable effects of pH reduction). • H2 receptor antagonists do not affect the pH of the fluid already in the stomach, only future production. Onset of action is 20–30 minutes (ideally administered 60–90 minutes prior to induction). Ranitidine 50 mg IV (dilute in 20 mL NS or D5W). Famotidine 20–40 mg IV. • Proton pump inhibitors do not affect the pH of the fluid already present in the stomach, only future production. Pantoprazole is available in IV formulation and 40 mg IV may be administered. • Promotility agents can be used to decrease the volume of gastric contents by increasing gastric emptying; can also increase LES tone. Metoclopramide for adults: 10–15 mg IM or IV; pediatrics 0.1–0.2 mg/kg IM or IV. Special Concerns for Informed Consent

• Increased risk of aspiration during deep sedation and induction/emergence of anesthesia. Deep sedation may not be an option; may have to consider lighter levels or general endotracheal anesthesia. • Patient will need to be fully awake with full recovery of protective airway reflexes prior to extubation. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with a cuffed endotracheal tube. • Deep sedation may impair upper airway reflexes; may need to consider lighter levels or no sedation.

Monitors

Standard ASA monitors

Induction/Airway Management

• Preoxygenation • Standard induction for low-risk patients (based on history) • RSI for high-risk patients. A true rapid sequence involves administering the induction agent and muscle relaxant in succession without assessing the ability to bag-mask ventilate the patient; the endotracheal tube is placed as soon as muscle relaxation has set in. Cricoid pressure (Sellick’s maneuver) is maintained prior to induction and until tracheal tube placement is confirmed. A modified RSI involves minimal ventilation with an airway pressure <20 cm H2O; cricoid pressure is maintained in the same manner.

• Induction in the “head-up” position; reverse Trendelenburg is preferred over “back up.” Reverse Trendelenburg takes advantage of gravity and decreases passive reflux. The “back up” position can increase intragastric pressures. • Awake intubation in cases of severe GERD history or “potential full stomach” – this technique aims to complete an endotracheal intubation in a patient whose airway reflexes and esophageal sphincter tone remain intact as it is undertaken with only topicalization of the airway to blunt reactivity, prior to induction of anesthesia. • Cuffed endotracheal tube is the preferred airway device to decrease the entry of gastric contents into the lungs. The ProSeal LMA may be considered for lower risk cases, since despite it being a supraglottic airway, it also includes a channel through which the stomach can be emptied (via suction).

Maintenance

Consider the placement of an orogastric tube to suction stomach contents and decrease volume. May leave in place to allow for suctioning prior to extubation. Extubation/Emergence

• Suctioning gastric contents prior to emergence • Consider readministration of antacid, H2 blockers, or promotility agents prior to extubation. • Standard criteria. Patient should be fully awake, muscle relaxation reversed, and capable of protecting their airway. • Elevated head of bed

POSTOPERATIVE CARE BED ACUITY

• Dependent on surgical procedure and patient comorbidities. • If aspiration is noted or suspected, the airway is unstable, or there are poor airway reflexes, a higher level of care to an ICU or step-down unit may be warranted.

MEDICATIONS/LAB STUDIES/ CONSULTS

• Patients may present in the recovery room with chest pain secondary to reflux. Lifethreatening causes (cardiac, pulmonary) should be considered and ruled out, as appropriate, despite the possibility of GERD. • Gastroenterology consult if needed to assess severity of GERD and sequelae.

COMPLICATIONS

• Aspiration pneumonia • Aspiration pneumonitis • Postoperative chest pain • Postoperative pulmonary complications

REFERENCES

1. JeskeHC. Preoperative administration of esomeprazole has no influence on frequency of refluxes. J Clin Anesth.2008;20:191–195. 2. SchiemanC, GrondinSC. Paraesophageal hernia: Clinical presentation, evaluation, andmanagement controversies. Thorac Surg Clin.2009;19:473–484. 3. RichterJE. The many manifestations of gastroesophageal reflux disease:Presentation, evaluation, and treatment. Gastroenterol Clin NorthAm.2007;36:577–599. 4. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: Application of healthy patients undergoing elective procedures. A report by the American Society of Anesthesiologists Task Force on Preoperative Fasting. Anesthesiology. 1999;90:896–905. 5. Cotton BR, Smith G. The lower esophageal sphincter and anaesthesia. Br Jour of Anes. 1984;56:37. • Hardy JF. Large volume gastroesophageal reflux: A rationale for risk reduction in the perioperative period. Can J Anesth. 1988;35:162–173. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary aspiration • Hiatal hernia • Postoperative pulmonary complications

CODES ICD9 530.81 Esophageal reflux ICD10 K21.9 Gastro-esophageal reflux disease without esophagitis

CLINICAL PEARLS

• GERD can place a patient at increased risk for aspiration and respiratory sequelae. • A thorough history-taking, appropriate premedication, and tailored anesthetic plan are paramount to patient safety.

GASTROINTESTINAL BLOOD FLOW Megan M. Freestone-Bernd, MD Mary E. McAlevy, MD

BASICS DESCRIPTION

• The splanchnic circulation consists of the blood flow to the stomach, intestines, pancreas, liver, and spleen. • At rest, the splanchnic circulation receives 15–25% of the cardiac output; this is equivalent to ~30 milliliters of blood per minute per 100 grams of tissue (30 mL/min/100 g) and can reach 250 mL/min/100 g. • Splanchnic circulation passes through the liver prior to entering the inferior vena cava and back into the general circulation. PHYSIOLOGY PRINCIPLES

• Blood flow increases sequentially along the digestive tract as digestion occurs. • Vasodilation of the splanchnic circulation increases to augment blood flow during digestion. It is regulated by (1): – Parasympathetic nervous system stimulation which increases glandular secretion of gastrin, secretin, vasoactive intestinal peptide, and cholecystokinin. – Possibly kallikrein and bradykinin (directly secreted by GI glands into the GI tract lumen) – β-agonists – Products of digestion such as fatty acids and glucose. – Decreased oxygen concentration from an increased metabolic rate during digestion. • Vasoconstriction of the splanchnic circulation is mediated by sympathetic nervous system stimulation, α-agonists, vasopressin, angiotensin, and endothelin (1). • Hepatic arterial buffer response (HABR) describes the ability of the body to protect the liver during low-flow states by increasing hepatic arterial flow when portal venous blood flow is decreased. It is hypothesized that the buildup of adenosine in low-flow states is responsible for the vasodilation of the hepatic artery (1). ANATOMY

• Celiac artery. Branches off the abdominal aorta and then divides into the gastric artery which supplies the stomach. The gastric artery divides into the splenic artery which supplies the spleen and pancreas. • Superior mesenteric artery. Branches off the abdominal aorta and forms smaller arteries that supply the small intestine and pancreas. • Inferior mesenteric arteries. Branches off the abdominal aorta and forms smaller arteries that supply the large intestine. • Superior and inferior mesenteric arteries. Form arcading arterial branches that allow multiple pathways for blood flow and decreases the risk of ischemia.

• Portal vein. Venous blood leaves the stomach, spleen, pancreas, and intestine through the portal vein, which provides about 70% of the blood supply to the liver. The remainder of the hepatic blood supply comes from the hepatic artery. • Hepatic vein. Drains the liver (portal vein and hepatic artery) and empties into the inferior vena cava.

DISEASE/PATHOPHYSIOLOGY

• Acute circulatory failure – Splanchnic blood flow may either be reduced proportionately or disproportionately, as related to systemic perfusion. Oxygen supply to the liver does not decrease until more than 30% of the total blood volume is lost due to HABR. Additionally, the decrease in perfusion is variable; the celiac trunk may receive less blood flow than the superior mesenteric, inferior mesenteric, and hepatic arteries (1). – Patients with right ventricular failure are at increased risk of developing severe liver dysfunction. There may be a 20-fold increase in either serum alanine or aspartate aminotransferase. This is reversible and is usually seen in patients with documented systolic BP <75 mm Hg for greater than 15 minutes (1). • High sympathetic stimulation states such as shock, hemorrhage, or hypovolemia can result in: – Vasoconstriction of the splanchnic circulation. This may provide as much as 200–400 mL of blood back into the general circulation (high capacitance). – Decreased splanchnic blood flow, as described above. • Hemodilution. Studies have shown that there is an overall increase in the blood flow to the splanchnic circulation; this is believed to preserve oxygenation/tissue perfusion (1). • Portal hypertension can occur from cirrhosis. It describes impaired blood outflow from the portal bed and an increase in splanchnic blood flow. Eventually, the increased pressure in the portal bed, combined with a lack of drainage, results in the formation of collateral circulation to other areas of the general circulation. These collateral vein sites cause caput medusa, hemorrhoids, and esophageal varices (2). • Mesenteric occlusion activates visceral afferent sympathetic fibers secondary to ischemia of the abdominal visceral organs, severe hypoxia, and the release of bradykinin and prostaglandins. This results in a reflex increase in arterial BP, heart rate, and cardiac contractility. The reflex is more profound with superior mesenteric artery occlusion than with celiac artery occlusion.

PERIOPERATIVE RELEVANCE

• Pneumoperitoneum for laparoscopic surgical procedures may also cause decreased splanchnic blood flow. At insufflation pressures of 12–15 mm Hg, the intra-abdominal pressure is greater than normal portal circulation pressure. There is a reduction in cardiac output and mesenteric vasoconstriction resulting in decreased organ perfusion and portal venous flow (3). • Cardiopulmonary bypass (CPB) causes a systemic inflammatory response that may lead to increased GI permeability related to ischemia/reperfusion, and/or inflammation. During CPB, GI blood flow does not change but mucosal blood flow may decrease by as much as 50%. Perioperative volume loading and early postoperative enteral nutrition may help

improve mucosal blood flow. • Supraceliac aortic cross clamping. Aortic clamping results in vasodilation proximal to the clamp (to decrease myocardial afterload) and vasoconstriction distally (to maintain perfusion pressure). Supraceliac clamping can have profound hemodynamic changes as compared to more distal clamping (e.g., infrarenal): – Increased preload from vasoconstriction of the splanchnic vasculature and volume shifting to the central circulation. – Increased afterload from the mechanical clamp. With infrarenal clamping, vasodilation of the splanchnic vasculature can help alleviate the increase in afterload. – Increased myocardial work. This may be poorly tolerated in patients with poor LV function due to increased myocardial work and oxygen consumption. Myocardial ischemia and LV failure can result if not properly anticipated. Aggressive treatment may be performed with vasodilators such as nitroprusside, nicardipine, and propofol.

REFERENCES

1. Jakob SM. Splanchnic blood flow in low-flow states. Anesth Analg. 2003;96:1129–1138. 2. Cichoż-Lach H, Celiński K, SŁomka M, et al. Pathophysiology of portal hypertension. J Pharmacol. 2008;59, Suppl 2:231–238. 3. Sammour T, Mittal A, Loveday BPT, et al. Systematic review of oxidative stress associated with pneumoperitoneum. Br J Surg. 2009;96:836–850.

ADDITIONAL READING

• Mitsuoka H, Kistler EB, Schmid-Schönbein GW: Generation of in vivo activating factors in the ischemic intestine by pancreatic enzymes. Proc Natl Acad Sci. 2000;97:1772–1777.

See Also (Topic, Algorithm, Electronic Media Element) • Abdominal aortic aneurysm, suprarenal • Cirrhosis • Laparoscopy • Isovolemic hemodilution • Cardiopulmonary bypass (CPB)

CLINICAL PEARLS

• Vasopressin and drugs that act as α-agonists will cause intestinal vasoconstriction. • β-agonists will cause intestinal vasodilation. • The HABR compensates during low venous blood flow to the liver by increasing hepatic arterial blood flow. • Splanchnic blood flow may be decreased due to pneumoperitoneum depending on the insufflation pressure used, anesthetic technique, and patient positioning (3). • Damage to the GI mucosa during CPB may be decreased by perioperative volume loading (1).

GASTROSCHISIS Joel Stockman, MD Swati Patel, MD

BASICS DESCRIPTION General

• Gastroschisis presents as the evisceration of the gut through a 2–3 cm defect in the anterior abdominal wall and lateral to the umbilicus; it usually occurs on the right. The abdominal wall and covering (sac) are absent. • The pathogenesis is poorly understood, but four mechanisms have been proposed: – Teratogenic exposure during the 4th week of development can hinder embryonic mesenchymal differentiation. – Amniotic membrane rupture at the umbilical cord during physiologic herniation or later secondary to delayed umbilical ring closure. – Abnormal right umbilical vein leading to growth impairment and viability of the mesenchyme, resulting in a skin defect and rupture. – Intrauterine occlusion of the omphalomesenteric artery leading to ischemia and atrophy of the abdominal muscles (1). • Management includes surgical correction involving either of two modes of closure (2). – Staged silo repair with delayed closure (spring-loaded versus stitched). Spring-loaded silo can be placed at the bedside, without the need for general anesthesia, whereas the stitched silo requires placement in the operating room. Delayed closure in the operating room occurs once abdominal contents are successfully reduced (2–7 days). – Primary closure can lead to ventilatory compromise, impede venous return, or cause aortocaval compression secondary to increased intra-abdominal pressure from direct compression (abdominal compartment syndrome).

Position Supine

Incision

Midline closure of present defect Approximate Time

Dependent on the size of the defect; ∼2 hours EBL Expected

Dependent on the extent of adhesions Hospital Stay

Approximately 45 days (2)

Special Equipment for Surgery

Ventilator with pressure control (PC) capability and spirometry EPIDEMIOLOGY Incidence

• Approximately 4/10,000 births • Increased risk associated with decreasing maternal age; greatest in women <20 years of age (1).

Prevalence

The male to female ratio is 1.5:1. Morbidity

• Infants with gastroschisis experience significant delays in starting and reaching full feeding support and may require prolonged total parenteral nutrition (TPN) support (3)[C]. – Extensive intestinal resection may result in short-gut syndrome. – Constriction of mesentery may cause intestinal atresia and decreased absorptive capacity of the gut. – Closed loop obstruction from volvulus or malrotation of the midgut.

Mortality

Current survival appears to be >85%. Postponed surgical management and the develop of abdominal compartment syndrome are associated with a worsened prognosis (4)[C]. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Fluid and heat loss are a primary focus. It can be minimized by using a warm, moist, sterile saline-soaked gauze or plastic bowel bag as well as ensuring a neutral thermal environment. • Extruded bowel is susceptible to infection, so broad spectrum antibiotics should be started. • Ventilatory compromise may be present prior to repair secondary to prematurity, decreased FRC from impaired diaphragm excursion during reduction in extruded bowel, and during primary closure. • Additionally a primary closure can present as an “abdominal compartment syndrome” and care must be taken to prevent this devastating complication.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Acid–base status should be closely monitored; respiratory compromise can occur secondary to the defect • Gastroesophageal reflux is not uncommon.

History

• Defect is typically identified on the prenatal ultrasound.

• Malabsorption and intestinal fixation (secondary to chronic exposure to amniotic fluid) may accompany the abnormality. • Non-GI abnormalities are uncommon. • Need for preoperative intubation is dependent on respiratory and acid–base status and degree of prematurity. Signs/Physical Exam

• Defect typically to the right of the umbilicus and measures <5 cm • Intestine may show varying degrees of inflammation and edema. This is dependent on the magnitude of ischemic injury caused by mesenteric compression and amniotic fluid exposure (implications include fluid losses and increased bleeding). • Observe for obvious signs of hypovolemia.

MEDICATIONS

• Broad spectrum antibiotics • Histamine-2 (H2) receptor blockade • TPN

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC • Electrolytes • Type and screen; depending on starting hematocrit and comorbidities, consider crossmatching 10–20 cc/kg. • Arterial blood gas (ABG) • CXR • Echocardiogram

CONCOMITANT ORGAN DYSFUNCTION

• Rare, but may be related to prematurity. • Cardiac anomalies (most commonly PDA, ASD, VSD) present in ∼4% of infants (5)[C].

TREATMENT PREOPERATIVE PREPARATION Premedications Not anticipated

Special Concerns for Informed Consent

• Need for continued postoperative intubation • Transfusion unlikely secondary to repair, but if comorbidities increase likelihood, risks of transfusions should be discussed.

Antibiotics/Common Organisms

Broad spectrum antibiotics are used to prevent peritoneal cavity contamination. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia for primary closure • Sedation can be administered in the neonatal intensive care unit (NICU) in intubated patients (ketamine and/or fentanyl, midazolam) for abdominal reduction via a silo device • Neuraxial technique (epidural or caudal catheter) has been described for aiding with reduction of extruded bowel; it may also allow for early extubation in patients with small defects. May not be necessary for patients who will remain intubated and sedated for several days postoperatively.

Monitors

• Standard ASA monitors with a pulse oximeter above and below the diaphragm to assess lower extremity perfusion with abdominal closure. • Consider arterial line for serial ABGs to assess potential abdominal compartment syndrome. • Foley catheter for fluid resuscitation assessment. • Surgical (tunneled) central line placement may be considered for future prolonged TPN administration. Additionally, it allows for monitoring of central venous pressures that may guide fluid management and assure adequate venous return once the abdomen is closed. • If no central access will be placed, adequate IV access (at minimum, one well running IV) must be established prior to the start of surgery. • Umbilical arterial line or venous line may be placed in the NICU to aid with BP monitoring and volume resuscitation. However, they may need to be removed during abdominal closure if it is in the surgical field. Preoperative discussion with surgeons is warranted.

Induction/Airway Management

• Decompression of the stomach with suctioning via an orogastric or nasogastric (NG) tube may decrease the risk of aspiration. Additionally, decreasing bowel distention can increase the likelihood of successful abdominal closure. • Rapid sequence IV induction is indicated. Care with (or avoidance of, if possible) bag mask ventilation if possible. Drugs should be tailored to the patient’s underlying conditions; those without significant comorbidities and who are adequately volume resuscitated may tolerate a propofol induction. Alternatively, etomidate or ketamine and/or narcotics may be appropriate when cardiac anomalies are present. Rocuronium or succinylcholine may be used (potential risk factors for succinylcholine must be considered prior to use). • Age/size appropriate ETT should be placed; the leak should not prevent the ability to adequately ventilate the patient once the bowel is reduced and the abdomen is closed. Appropriate leak will depend on the size of the defect and underlying lung disease (20–30 mm Hg may be required). A low profile cuffed ETT may be considered to allow for dynamic changes in ventilatory pressures required but care must be taken to maintain the leak below 30 mm Hg (pressure at which mucosa may be prone to ischemia).

Maintenance

• Fresh gas. Avoid nitrous oxide as it can distend bowel. The oxygen-air mixture should be

titrated to maintain the SpO2 in the mid-90s to decrease the risk of retinopathy of

prematurity. • MAC. Unlike infants who have a higher MAC requirement than adults, neonates have a decreased (up to 25% less) MAC requirement. • Opioid technique with judicious use of volatile anesthetics (to avoid hypotension) is indicated. High dose narcotics, such as fentanyl (5–15 μg/kg) can be titrated as tolerated for intraoperative maintenance, especially when extubation is not planned. • Muscle relaxation facilitates closure of the abdomen. • Ventilation parameters. Monitor peak inspiratory pressures (PIP) and tidal volumes (TV) throughout abdominal closure. An increase in PIPs or a decrease in TVs or SpO2% may

mean abdominal closure will not be tolerated. Maximum allowable PIP is dependent on underlying lung disease, degree of prematurity, and need to avoid barotrauma; but in general, pressures >25 mm Hg should be avoided. Additionally, high frequency oscillatory ventilation may be required if conventional ventilation is inadequate. Serial ABGs may guide management. – Fluid requirements will be high. Up to 10–200 mL/kg/hr may be required during primary closure and is dependent on the level of bowel exposure. – Use isotonic fluids or colloid (albumin) for volume resuscitation. – Warm all fluids and maintain body temperature with forced air warmer and radiant heater. Additionally, room should be warmed to (70–72°F) prior to start of case. – Run TPN or dextrose containing IV fluids (usually D10) at ½ maintenance to avoid intraoperative hyperglycemia. Blood sugar should be monitored closely. • Intra-abdominal pressure monitoring via intragastric (NG tube) or intravesicle catheter (Foley) can guide surgeons on whether abdominal closure can be tolerated; should be maintained <20 mm Hg. Decreased preload secondary to compression of the inferior vena cava or decreased urine output secondary to diminished renal blood flow can provide further evidence of increased intra-abdominal pressure.

Extubation/Emergence

• Postoperative ventilation is common in most neonates for 24–48 hours, especially for larger defects. • Immediate postoperative extubation may be considered for small defects. Also consider the size of the patient, associated defects, hemodynamic stability, and intraoperative events.

POSTOPERATIVE CARE BED ACUITY

NICU. Postoperative ventilation is common in most neonates for 24–48 hours. ANALGESIA

• Ketamine and/or opioid for staged NICU closure • Opioid +/– benzodiazepine following primary closure • Epidural/caudal catheters may be appropriate (institution dependent)

COMPLICATIONS

• Infection – GI (necrotizing enterocolitis), ventilatory, wound, etc. • Prolonged postoperative ileus • Abdominal compartment syndrome, which may impede splanchnic blood flow, resulting in intestinal ischemia or necrosis. • Hepatotoxicity secondary to prolonged parenteral nutrition. • Hypertension secondary to decreased renal perfusion.

PROGNOSIS

Long-term bowel complications are not uncommon (e.g., malrotation, volvulus, small bowel obstruction, gastroesophageal reflux) (2,3).

REFERENCES

1. Feldkamp et al. Development of gastroschisis: Review of hypotheses, a novel hypothesis, and implications for research. Am J Med Genet Part A. 2007;143:639–652. 2. Banyard D, Ramones T, Phillips SE, et al. Method to our madness: An 18-year retrospective analysis on gastroschisis closure. J Pediatr Surg. 2010;45(3):579–584. 3. Kitchanan S, Patole SK, Muller R, et al. Neonatal outcome of gastroschisis and exomphalos: A 10-year review. J. Paediatr Child Health. 2000;36:428–430. 4. Tasai MH, Huang HR, Chu SM, et al. Clinical features of newborns with gastroschsis and outcomes of different initial interventions: Primary closure versus staged repair. Pediatr Neonatol. 2010;51(6):320–325. 5. Kunz LH, Gilbert WM, Towner DR. Increased incidence of cardiac anomalies in pregnancies complicated by gastroschisis. Am J Obstet Gynecol. 2005;193:1248–1252. See Also (Topic, Algorithm, Electronic Media Element) • Insensible fluid losses • Omphalocele

CODES ICD9 756.73 Gastroschisis ICD10 Q79.3 Gastroschisis

CLINICAL PEARLS

• Unlike omphaloceles, gastroschisis is usually an isolated defect. • Fluid resuscitation is a key element of anesthetic management, as the exposed bowel has the potential for significant insensible fluid losses. • Careful monitoring for changes in respiratory function during closure is mandated.

GERIATRIC PHYSIOLOGY Stephen Dechter, DO Bruce Vrooman, MD

BASICS DESCRIPTION

• Aging correlates with a physiologic decline and increase in prevalence of disease. • Care of geriatric patients is growing in number and need and will continue to do so; it is important for the anesthesia provider to understand the accompanying physiology/pathophysiology that results with age. PHYSIOLOGY PRINCIPLES

• Neurologic system – Cerebral blood flow (CBF) and volume decrease due to a combination of reduced cerebral metabolism and cerebral vascular changes including atherosclerosis, decreased vessel wall compliance, and vessel narrowing. – Short-term memory, learning, and information processing decrease. – Temperature regulation is impaired; there is decreased autonomic vasomotor control and sensitivity to changes. • Cardiovascular system – Systolic blood pressure (SBP) and diastolic blood pressure (DBP) increase due to decreased atrial and vessel elasticity (1)[A]; there is a resultant widened pulse pressure. – Atrial contraction becomes increasingly important due to impaired diastolic filling (2)[A]. – Resting and maximum heart rate (HR) decrease due to a reduction in beta-adrenergic responsiveness and cardiac contractility; the general rule is maximum HR = 220–age. – Left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and stroke volume increase due to myocardial structural changes (contractility, hypertrophy, and enlargement). – Resting and exercise cardiac output (CO) remain normal due to Frank–Starling mechanisms (2)[A]. – Valves thicken and calcify – Maximal oxygen consumption (VO2) decreases due to loss of body muscle mass, vascular

structural changes, and gas exchange systems (3)[A]. – Baroreflexes become impaired due to reduced arterial compliance leading to impaired mechanical transduction of arterial pressure changes and reduced cardio-vagal neural outflow. • Pulmonary system – Oxygen gas exchange is impaired due to increased ventilation/perfusion imbalances; lower PaO2 baseline values and normal SpO2% are seen. – Carbon dioxide excretion is normal

– Hypercapnic and hypoxic respiratory responses are impaired; there is also a reduced ability to handle congestive heart failure (CHF), infection, and obstruction. – Total lung capacity (TLC) is normal (4)[A]; residual volume (RV) can increase by 50%; vital capacity (VC) can decrease by 50–75% due to decreased chest wall compliance combined with air trapping. – Functional residual capacity (FRC) increases due to stiffer, ossified thoraxes by ~3% per decade (decreased compliance, increased outward forces. Closing volume (CV), however, decreases to a greater extent and leads to airway closure, atelectasis, and V/Q shunting. – FEV1 decreases by 20–40 mL/year; forced vital capacity (FVC) decreases in males

>females; results in increased breathing energy expenditure (up to 20%) due to changes in small peripheral airways and reduced chest wall compliance. – Respiratory muscle strength, cough, and ciliary function decrease. • Hepatic system – Hepatic mass and blood flow decrease due to cell loss and reduction in the number of mitochondria with a compensatory increase in hepatocyte and mitochondrial size to preserve function. – Drug metabolism decreases • GI system – Esophageal function and emptying decrease – Gastric motility, acid secretions, and absorption decrease (calcium, iron, zinc, folic acid, B12) – Colonic muscle contraction and rectal perception decrease • Renal system – Renal mass, tubular mass, renal blood flow, creatinine clearance, and glomerular filtration rate decrease (1% per year after age 30) due to atrophy of afferent and efferent arterioles, generalized sclerosis, and comorbid disease (primary renal failure, atherosclerosis). – Drug clearance decreases – Sodium, potassium, hydrogen ion concentration, and vascular volume usually have no change. • Immunologic system – Risk of infection increases due to impaired immune function secondary to decreased functional competence of NK cells, granulocytes, macrophages, impaired phagocytosis and chemotaxis-impaired cytokine production, T and B cell deficits, and increased number of autoantibodies. • Endocrine system – Insulin resistance increases; insulin secretion becomes impaired; FBS and cortisol remain normal. – Thyroid hormone regulation decreases; T4 stays normal. – Testosterone, estrogen, and growth hormone decrease. • Musculoskeletal system – Muscle mass, strength, and power decrease – Bone mineral density decreases – The increase in weight and decrease in body water/lean body mass lead to an increase in body fat%. Fat-soluble drugs (fentanyl, benzodiaze- pines) have an increased volume of

distribution (VD). Water-soluble drugs (ethanol, digoxin, gentamicin) have a decreased VD

(5)[A]. • Integumentary system – Connective tissue elasticity, moisture, and skin sensation decrease. – Collagen cross-linking increases and causes tissue fragility. This increases the risk of pressure ulcers and skin breakdown.

ANATOMY

• Brain weight: 15% decrease • Blood volume contraction: 20–30% • Liver volume: 24% decrease • Renal mass: 20% decrease

DISEASE/PATHOPHYSIOLOGY

• Neurologic diseases – Cerebrovascular accident (CVA) risk doubles each decade after age 55 (10-year probability of CVA in men is 5.9% at age 55, 13.7% at age 70, and 22.3% at age 80). – Dementias may be the result of genetic, autoimmune, infectious, vascular, or traumatic brain/neuronal damage. 10% of those aged 65 and older and 20% of those aged 80 and over have some form of dementia. – Increased incidence of glaucoma, cataracts, macular degeneration, and presbyopia. 4% of those aged 65 years and 16% of those aged 85 have visual impairment. – Hearing loss may cause social isolation and contribute to paranoid ideation. 20% of those aged 50 and 90% of those aged 80 have hearing loss. • Cardiovascular diseases – Hypertension (HTN) is often treated with antihypertensives. These drugs can have side effects including orthostasis, urinary frequency, dehydration, and fatigue. Prevalence is 44% at age 40 and 65% at age 70. – Arrhythmias. Treatment with antiarrhythmic medications, anticoagulation, and implantable pacemakers (5)[A]. Prevalence is 2% at age 60 and 10% at age 80. – Coronary artery disease (CAD) from plaque/cholesterol buildup can decrease coronary blood flow. Symptoms include substernal chest pain (33%), dyspnea (20%), weakness, malaise, worsening CHF, syncope, arrhythmia, or confusion. Prevalence is 20% at age 55 and 30% at age 75. – CHF symptoms include dyspnea and chest pain. Treatments with digoxin and diuretics have anesthetic implications. Prevalence is 22% at age 60 and 70% at age 80. – Valvular disease from thickened and calcified valve tissue may develop. Symptoms range from asymptomatic to dyspnea to fatigue. Treatment includes anticoagulation and valvular replacement. Prevalence is 40% at age 75–85 for mild disease and 13% for severe disease. • Pulmonary diseases – Obstructive sleep apnea (OSA) from blockage of the soft palate during sleep can result in increased work of the diaphragm/lungs and brief apneic episodes. Symptoms include fatigue, snoring, headaches, and HTN. Prevalence of sleep-disordered breathing is up to 30% in the elderly.

– Chronic obstructive pulmonary disease (COPD) may result from years of smoking. Prevalence is 20–40% in those aged >65. – Respiratory failure from coexisting disease (pneumonia, left ventricular failure) is more likely. Increased work of breathing on top of their baseline may increase. – Extubation may be delayed due to decreased ventilatory responses to hypoxia and hypercarbia, maximal breathing capacity, VC, cough strength, and clearance of secretions, as well as increased air trapping and V/Q mismatch. • Immunologic diseases – Cancer increases with age due to uninhibited cell growth with tumor formation and/or distant metastasis. Symptoms include weight loss, fever, chills, night sweats, and new onset back pain. Prevalence is 1% at age 50 and 4% at age 85. – Infectious response may be impaired. • Endocrine diseases – Diabetes is associated with large and small vessel disease. Prevalence is 10% at age 50 and 20% over age 75. • Musculoskeletal diseases – Osteoarthritis increases presentation to the OR for joint replacements. Prevalence increases from 27% at age 70 to 44% at age 80. – Osteoporosis may result in an increased incidence of fractures. Prevalence in women over 50 is 4% and 44% at 80.

PERIOPERATIVE RELEVANCE

• Neurologic relevance. Postoperative cognitive dysfunction (POCD) is common in the elderly. At 3 months after surgery, the incidence of POCD was 9.9% in patients >60 years old versus 2.8% for the control group. • Cardiac relevance. Increased risk of arrhythmias, HTN, hypotension; induction time can be affected (inhalational agents can have an increased onset, and intravenous agents a decreased onset time). • Pulmonary relevance. Increased risk of pulmonary edema, pneumonia, aspiration (impaired cough and mucociliary clearance). • Hepatic relevance. Impaired metabolism requires a decreased dosage of induction agents (e.g., propofol and inhalational agents); results in prolonged effects of opioids, benzodiazepines, local anesthetics, and neuromuscular blocking drugs. • Renal relevance. Low muscle mass decreases serum creatinine values. A “normal” value may be abnormal. Drug excretion may be impaired resulting in prolonged half-life (t1/2); fluid

balance may be impaired. • GI relevance. Increased risk of aspiration due to impaired gastric emptying and esophageal motility. • Musculoskeletal relevance. Weakness, prolonged recovery, poor mobility, increased risk of DVT, pneumonia, and decubitus ulcers. See Table

REFERENCE

1. Franklin SS, Gustin W 4th, Wong ND, et al. Hemodynamic patterns of age-related changes

in blood pressure. The Framingham Heart Study. Circulation. 1997;96(1):308–315. 2. Lakatta EG, Levy D. Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises. Circulation. 2003;107(2):346–354. 3. Fleg JL, Lakatta EG. Role of muscle loss in the age-associated reduction in VO2 Max. J Appl Physiol. 1988;65(3):1147–1151. 4. Janssens JP, Pache JC, Nicod LP. Physiological changes in respiratory function associated with aging. Eur Respir J. 1999;13(1):197–204.

5. Mangoni AA, Jackson SHD. Age-related changes in pharmacokinetics and pharmacodynamics: Basic principles and practical applications. Br J Clin Pharm. 2004;57(1):6–14.

6. Qaseem A, Snow V, Shekelle P. Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008;149(6):404–415.

ADDITIONAL READING

• Abass IB. The biology and physiology of aging. West J Med. 1990;153(6):641–645. • Kitzman DW, Diastolic heart failure in the elderly. Heart Fail Rev. 2002;7(1):17–27. • U.S. Census Bureau. http://www.census.gov/ See Also (Topic, Algorithm, Electronic Media Element) • Respiratory physiology • Diabetes mellitus • Coronary artery disease

CLINICAL PEARLS

• Increased perioperative mortality is due to multisystem changes related to aging. • Caution is warranted with induction agents and medications due to impaired metabolism (renal, pulmonary, cardiac, hematologic, hepatic) that can lead to overdose and death. • Monitor body temperature carefully due to impaired thermoregulation. • Careful monitoring of fluid balance, electrolytes, and oxygen saturation is necessary. • Caution with use of NSAIDs (renal failure, GI side effects) and opioids (pulmonary depression, sedation, AMS).

GESTATIONAL DIABETES Peter Drocton, MD Mark Zakowski, MD

BASICS DESCRIPTION

• Diabetes mellitus (DM) is a common metabolic disorder. – Type 1 DM is primarily characterized by insulin deficiency. – Type 2 DM is primarily characterized by insulin resistance. • Gestational diabetes mellitus (GDM) implies that the first occurrence is during pregnancy and brought on by the hormonal changes of pregnancy. • Pregestational DM occurs before pregnancy • Good glycemic control has been shown to reduce perinatal complications; 60–95 mg/dL has been used as a target range. EPIDEMIOLOGY Prevalence

Gestational diabetes has an ∼7% incidence; it is increased among certain ethnic groups (Latino, African-American) Prevalence

Not available Morbidity

• Maternal morbidity associated with – Diabetic ketoacidosis (DKA) in ∼1–2% of diabetic pregnancies, related to Type I DM – Severe hypoglycemia occurs in ∼50% of patients, higher incidence in Type 1 DM – Pregnancy-induced hypertension (PIH) and preeclampsia occur with greater frequency in parturients with GDM – Progression of end-organ damage including retinopathy, nephropathy, and neuropathy – Autonomic cardiovascular dysfunction • Neonatal morbidity characterized by – Hypoglycemia – Hypocalcemia – Respiratory distress syndrome from delayed release of surfactant in lungs – Hyperbilirubinemia – Macrosomia with associated shoulder dystocia and birth injuries – Birth defects (especially with pregestational DM) Mortality

Pregestational DM perinatal mortality rate ∼5%

ETIOLOGY/RISK FACTORS

• Etiology of GDM: Presumed to be due to hormonal changes of pregnancy in order to spare glucose for fetal utilization. • Risk factors: Obesity, advanced maternal age, previous history of GDM, family history of DM.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Normal pregnancy results in – Decreased insulin sensitivity by ∼50%. – Increased insulin requirements due to increases in anti-insulin hormones of pregnancy. Human placental lactogen (HPL) has a growth hormone (GH)-like effect that increases glucose availability for the fetus. • Fetus – Maternal insulin does not cross the placenta – Fatty acids cannot be utilized for energy until the 3rd trimester • Gestational diabetes – Impaired beta-cell function results in insufficient insulin release – Insulin sensitivity is further decreased, compared to non-GDM pregnancies • Impaired glucose control can result in placental degeneration and calcification • Pain can elevate cortisol levels and further worsen insulin sensitivity

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Anticipate added risks with general anesthesia such as – Difficult intubation due to stiff-joint syndrome (generally Class C) – Aspiration from diabetic gastroparesis – Autonomic cardiovascular dysfunction and hemodynamic instability • Regional anesthesia with either spinal or epidural has been shown to be effective and preferred to general anesthesia. Vasopressor therapy, however, may be needed following bolus doses. • Delivery complications include unexplained fetal demise with increasing gestational age. Thus, it is suggested that patients with GDM should be delivered by 40 weeks; pregestational diabetics should be delivered by 39 weeks.

PREOPERATIVE ASSESSMENT SYMPTOMS

If undiagnosed, the patient may complain of increased thirst, frequent urination, blurry vision, or orthostatic symptoms History

• Assess glycemic control, episodes of hyperglycemia, and hypoglycemia • Evidence of cardiovascular disease, autonomic dysfunction, or other coexisting morbidities including neuropathies

Signs/Physical Exam

• Hypertension may be present secondary to preeclampsia/PIH. • General assessment of cardiac and pulmonary status • Brief neurologic exam to look for peripheral nerve palsies and neuropathies • “Prayer sign” – inability to closely approximate the palms and fingers when hands placed together may imply stiff-joint syndrome and potential difficult intubation due to poor neck extension. TREATMENT HISTORY

Fasting glucose >105 g often requires insulin therapy if diet and exercise fail to control the condition. MEDICATIONS

• Oral hyperglycemic agents (glyburide) may be used. • Metformin is not generally used, but pregestational DM patients may have continued to take it. • Insulin regimen should be reviewed with consideration for insulin infusion. • Pregestational DM patients have a 50% increase in insulin requirement by term. • Anticipate sharply decreased insulin needs soon after delivery (as much as 15% on the first postpartum day). DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Typically diagnosed on screening at 24–28 weeks gestation, either via fasting glucose (>126 mg) or oral glucose tolerance test (OGTT) (>200 mg at 2 hours). • Frequent glucose measurements • Hemoglobin (Hgb) A1C: 4–6% normal, >7% indicates impaired control. • Platelets, coagulation factors, fibrinogen, and proteinuria in cases with suspected PIH/preeclampsia. • Fetal status followed by more frequent nonstress tests and biophysical profile • Fetal lung maturity testing by amniocentesis for indications of maturity: Lecthicin:sphingomyelin ratio >2, presence of phosphatidyl glycerol (component of surfactant) and Lamellar bodies (surfactant vacuoles). CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular effects including hypertension, heart disease, and renal disease • Neuropathy • Proliferative retinopathy • Delayed fetal production of surfactant

CIRCUMSTANCES TO DELAY/CONDITIONS

• Elective Cesarean section without documentation of fetal lung maturity at <39 weeks gestation • Moderate-to-severe hyperglycemia or hypoglycemia if fetal conditions allow time to treat and optimize.

CLASSIFICATIONS

• White classification during pregnancy: – Class A1: Gestational, diet controlled – Class A2: Gestational, on insulin or oral antihyperglycemic • White classification for pre-existing diabetes – Class B: Diagnosis of DM for <10 years – Class C: Diagnosis of DM for >10 years – Class R: DM complicated by retinopathy – Class F: DM complicated by nephropathy – Class T: DM with renal transplant

TREATMENT PREOPERATIVE PREPARATION Premedications

• Antacids (sodium bicitrate) and promotility agents (metoclopramide) • Adequate fluid resuscitation prior to induction of general or regional anesthesia

INTRAOPERATIVE CARE Choice of Anesthesia

Maternal safety is improved with regional anesthesia Induction/Airway Management

• Assessment for, and anticipation of, stiff-joint syndrome with reduced neck movement resulting in difficult intubation (Prayer sign) • Cardiovascular instability should be monitored for and may require greater vasopressor use.

Maintenance

• During labor, an insulin infusion may be utilized (0.8–1.0 units/kg) to keep glucose 70–90 mg/dL (tight control) or 80–100 mg/dL. Glucose infusion 5–10 g/hour may be needed if NPO • Carefully pad extremities during Cesarean sections; diabetics are more prone to nerve injuries/neuropathies • Judicious fluid administration in patients with cardiovascular disease or preeclampsia (increased risk of pulmonary edema) Extubation/Emergence

In intubated patients, consider a leak test prior to extubation. Increased airway edema may be present from excessive fluid administration.

FOLLOW-UP BED ACUITY

• Higher nursing acuity for insulin infusions • Coexisting moderate-to-severe maternal disease may warrant increased nursing care.

MEDICATIONS/LAB STUDIES/CONSULTS

• Continued glucose monitoring through the peripartum period • Can typically discontinue insulin infusion postdelivery

COMPLICATIONS

• Maternal – Hyperosmolar hyperglycemic state – Diabetic ketoacidosis – Subsequent pregnancies have a 40–50% risk of GDM – Development of type 2 DM (60%) – Increased risk for infection (impaired WBC effectiveness) • Neonatal – Respiratory distress syndrome requiring supplemental oxygen or intubation – Hypoglycemia requiring careful monitoring – Hyperbilirubinemia – Increased risk of developing GDM (females)

REFERENCES

1. ridijian G,Benjamin TD. Update on gestational diabetes. Obstet Gynecol Clin N Am. 2010;37:255–267. 2. Pani N, Mishra SB, Rath SK. Diabetic parturient – Anaesthetic implications. Indian J Anaesth. 2010;54:387–393.

ADDITIONAL READING

• American Diabetes Association • American Congress of Obstetricians and Gynecologists Practice Bulletin 30 Gestational Diabetes, Practice Bulletin 60 Pregestational Diabetes • World Health Organization

See Also (Topic, Algorithm, Electronic Media Element) • Diabetes mellitus • Pregnancy-induced hypertension

CODES ICD9 648.83 Abnormal glucose tolerance of mother, antepartum condition or complication ICD10 O24.419 Gestational diabetes mellitus in pregnancy, unsp control

CLINICAL PEARLS

• Avoidance of maternal hyperglycemia during pregnancy and labor allows for better maternal and neonatal outcomes. • Maintain tight glucose control; may need insulin and glucose infusion during labor. • PIH and preeclampsia are twice as likely to occur in the setting of GDM • Prayer sign can predict stiff-joint syndrome and the possibility of a difficult intubation. • Insulin requirement in the postpartum period decreases and requires constant vigilance. • Routinely check newborn glucose and evidence of hyperbilirubinemia.

GLOMERULAR FILTRATION RATE (GFR) Gregory E. R. Weller, MD, PhD

BASICS DESCRIPTION

• Glomerular filtration rate (GFR) is widely considered to be the best overall index of renal function. • GFR is the rate (volume per unit time) that plasma fluid is filtered by functioning nephrons and is used to detect, grade, and follow the course of kidney disease. Patients with a low GFR have a greater likelihood of the following: – Significant comorbidities. – Intraoperative and postoperative complications such as worsening of renal failure, cardiovascular complications, electrolyte disturbances, etc. • Despite its utility, GFR is not easily measured and attained. To that extent, it is often approximated by creatinine clearance (CCr) or other equations that estimate GFR based on serum creatinine (SCr), each with its own pros and cons. PHYSIOLOGY PRINCIPLES

• The kidneys receive ∼20–30% of the cardiac output. • Ultrafiltration: – Blood flows from the afferent arteriole, through the highly permeable renal glomerular capillaries, and out the efferent arteriole. – Plasma is filtered through these capillaries into the surrounding Bowman’s capsule. The ultrafiltrate then passes through the proximal tubule, loop of Henle, distal tubule, and collecting ducts while being subjected to tubular reabsorption and secretion, prior to being excreted as urine (the majority of glomerular filtrate is reabsorbed and returned to the systemic circulation). – The diameter of efferent arterioles is smaller than that of afferent arterioles, leading to a pressure gradient that is countered by osmotic and hydrostatic pressures and drives ultrafiltration. • Regulation of GFR: – Renal blood flow (RBF) and GFR are maintained via autoregulation across a wide range of mean arterial pressures (∼70–170 mm Hg). – Outside of this autoregulated range, GFR is dependent on systemic BP. Renal autoregulation can be impaired by chronic hypertension (HTN), hyperlipidemia, obesity, and insulin resistance. – The ratio of GFR:renal plasma flow (RPF) is the filtration fraction (FF), and under normal circumstances is ∼20%. Afferent arteriolar vasodilation or efferent arteriolar vasoconstriction will increase the FF to maintain a constant GFR in the setting of a decreased RPF. – GFR decreases by increased renal tubular flow (tubuloglomerular feedback).

– GFR decreases by sympathetic stimulation, via renin-angiotensin system-mediated constriction of renal afferent arterioles. • GFR measurement: – GFR can be calculated by measuring endogenous (e.g., creatinine) or exogenous (e.g., inulin) substances that have steady-state levels in blood, are freely filtered by glomeruli, and are not (or only minimally) secreted or reabsorbed in the renal tubules. GFR = (urine concentration × urine flow)/(plasma concentration) – GFR can be approximated by CCr, although this will generally overestimate GFR by 5– 20% due to small amounts of tubular creatinine secretion. Tubular secretion of creatinine can be competitively inhibited by cimetidine. – CCr is best measured with a 24-hour urine collection and spot steady-state serum measurements, but this is logistically challenging. – Creatinine is produced by the breakdown of creatine in skeletal muscle. Increased muscle mass (e.g., males, African-Americans) will lead to higher SCr at any level of CCr. Conversely, decreased muscle mass (malnutrition, paraplegia) will result in lower creatinine generation. – Numerous equations (see below “Equations”) have been developed that estimate CCr or GFR, based on factors including SCr, age, race, gender, height, weight, BUN, serum albumin, etc. – Most labs have recently changed SCr assays from an older alkaline picrate (Jaffe) chromographic technique to a newer enzymatic technique that iscalibrated to isotope dilution mass spectroscopy (IDMS). This results in ~5% lower SCr values, leading to adjustments in previous GFR estimation formulas. – A more recently investigated endogenous protein called cystatin C may offer improved GFR estimation compared to creatinine, but most estimation formulae still rely on SCr. • Normal values: – Normal GFR for adults is 110–130 mL/min per 1.73 m2. (GFR is usually reported adjusted for body surface area because renal function is proportional to kidney size, which in turn is proportional to body surface area; 1.73 m2 is considered the normal mean for healthy young adults.) – Premature infants have correspondingly lower GFR.

Pediatric Considerations

• Slightly higher for men versus women • GFR for full-term neonates is 15–40% that of adult values. GFR doubles over the first 2 weeks postnatally and then continues to increase slowly until reaching adult value at 1–2 years. • Use Schwartz formula for GFR estimation in pediatric patients. (The Cockcroft–Gault, Modification of Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulae were derived and validated using adult populations.)

Geriatric Considerations

• Elderly patients have lower muscle mass, which generates less steady-state creatinine, so their SCr can be deceptively low (i.e., a SCr that is normal for younger adults may reflect a significantly impaired GFR in the elderly).

• In the elderly, RBF and GFR are decreased due to vascular sclerosis and renal parenchyma atrophy. DISEASE/PATHOPHYSIOLOGY

• GFR < 60 mL/min/1.73 m2 defines chronic kidney disease. • GFR can decrease by half (e.g., 120 to 60 mL/min/1.73 m2) before becoming clinically apparent (due to large functional kidney reserves). • The prevalence of complications of chronic kidney disease increases significantly below 60 mL/min/1.73 m2. • Chronic kidney disease staging: – Stage 1: GFR > 90 mL/min/1.73 m2 (kidney damage with normal GFR) – Stage 2: GFR 60–89 (mild) – Stage 3: GFR 30–59 (moderate) – Stage 4: GFR 15–29 (severe) – Stage 5: GFR < 15 (kidney failure; on dialysis)

PERIOPERATIVE RELEVANCE

• Decreased preoperative renal function is a strong predictor for intraoperative and postoperative acute renal failure. • General anesthesia and, to a lesser extent, neuraxial anesthesia mildly and reversibly impair GFR. • Volatile anesthetic agents produce a dose-dependent decrease in RBF and GFR (and consequently urine output), an effect likely secondary to their negative impact on cardiac output and systemic BP. Volatiles do not directly affect autoregulation. • Chronic renal failure (CRF) can contribute to the following: – Anemia (decreased erythropoietin) – Electrolyte disturbances (e.g., hyperkalemia) – Heart disease (HTN, coronary artery disease, CAD) – Coagulopathy (decreased platelet function) – Hypoalbuminemia – Increased gastric volumes – Increased risk of infectious complications (e.g., sepsis) • CRF patients are often diabetic. • CRF patients may have arteriovenous (AV) fistulas that limit the placement of IV lines, arterial lines, and BP cuffs. • Perioperative management: – Drug doses must be adjusted for those drugs that have significant renal elimination, secretion, or metabolism such as antibiotics, some muscle relaxants (tubocurarine, pancuronium), H2-receptor blockers, morphine and meperidine metabolites, contrast agents, etc. – Maintain a low threshold for the placement of an arterial line (due to cardiac comorbidities and for arterial blood gases, ABGs) and central venous access (due to volume disturbances). – Carefully assess volume status intraoperatively and monitor fluid intake and urine output.

– Monitor electrolytes and consider replacement as needed.

EQUATIONS

Online calculators for each of these formulae are widely available (e.g., www.kidney.org/gfr).

• Cockcroft–Gault formula (1): – Published in 1976 – Estimates CCr – CCr = (140–Age) × Weight × (0.85 if Female)/(72 × SCr); where CCr is measured as mL/min, Age in years, Weight in kg, and SCr in mg/dL. – Does not account for race – Does not adjust for body surface area – Clearly demonstrates the dependence of CCr on age – Most drug-dosing guidelines for impaired renal function are based on Cockcroft–Gault estimates • 4-variable MDRD formula (2): – Published in 2000 – Estimates GFR – Based on patients enrolled in MDRD study – GFR = Const × (SCr)−1.154 × (Age)−0.203 × (0.742 if Female) × (1.210 if AfricanAmerican); where Const = 175 if the lab calibrates SCr to IDMS standard, or 186 if not; GFR is measured in mL/min/1.73 m2; Age in years; SCr in mg/dL. – Tends to underestimate GFR at higher (more normal) values above 60 mL/min/1.73 m2 – Does not adjust for body mass; will underestimate GFR for heavy patients • 6-variable MDRD formula (3): – Published in 1999 – Estimates GFR – Expanded version of MDRD formula – GFR = Const × (SCr)−0.999 × (Age)−0.176 × (0.762 if Female) × (1.18 if AfricanAmerican) × (BUN)−0.170 × (Albumin)+0.318; where Const = 160 if the lab calibrates SCr to IDMS standard, or 170 if not; GFR is measured in mL/min/1.73 m2; Age in yrs; SCr in mg/dL. – Tends to underestimate GFR at higher (more normal) values – Does not adjust for body mass; will underestimate GFR for heavy patients • CKD-EPI formula (4): – Published in 2009 – Estimates GFR – Developed by CKD-EPI in effort to improve on existing MDRD models – GFR = 141 × min(SCr/k,1)a × max(SCr/k,1)−1.209 × 0.993Age × (1.018 if Female) × (1.159 if African-American); where k is 0.7 for Females and 0.9 for Males; a is −0.329 for Females and −0.411 for Males; GFR is measured in mL/min/1.73 m2; Age in yrs; SCr in mg/dL. – More accurate and less biased than MDRD formulae, especially improved at higher GFRs • Schwartz pediatric formula (classic) (5):

– Published in 1976 – Estimates GFR in children – GFR = k × Height/SCr – k is 0.33 for premature infants, 0.45 for full-term infants, and 0.55 for children age 1–12 years – GFR in mL/min/1.73 m2; Height in cm; SCr in mg/dL • Schwartz pediatric formula (updated) (6): – Published in 2009 – GFR = 0.413 × Height/SCr – Reflects modern IDMS standardized SCr measurements

REFERENCES

1. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41. 2. Levey AS, Greene T, Kusek JW, et al. A simplified equation to predict glomerular filtration rate from serum creatinine (Abstract). J Am Soc Nephrol. 2000;11:155A (A0828). 3. evey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Ann Intern Med. 1999;130:461–470. 4. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612. 5. Schwartz GJ, Haycock GB, Edelmann CM Jr, et al. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics. 1976;58:259–263. 6. Schwartz GJ, Munoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20:629–637. www.kidney.org (National Kidney Foundation) Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function – Measured and estimated glomerular filtration rate. N Engl J Med. 2006;354:2473–2483. 7. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease. Am J Kidney Dis. 2002;39:S1–S266. Also available at www.kidney.org/professionals/kdoqi. See Also (Topic, Algorithm, Electronic Media Element)

• Chronic renal failure • Renal blood flow • Creatinine clearance

CLINICAL PEARLS

• GFR is considered to be the best overall index of renal function. • Estimate GFR using well-established, validated models based on SCr values: • Use CKD-EPI or modified MDRD formulae for clinical GFR estimates. • Use Cockcroft–Gault formula to estimate GFR for drug-dosing purposes. • Use modified Schwartz formula for children up to 12 years.

• Patients with low GFR (<60 mL/min/1.73 m2) have significant renal function impairment, are more likely to have important comorbidities (anemia, volume disturbances, electrolyte abnormalities, cardiac disease, etc.), and are at increased risk for intraoperative and postoperative complications. • Many drugs require reduced doses or dosing intervals (“renal dosing”) in patients with low GFR.

HEART TRANSPLANT Charles H. Brown IV, MD Nanhi Mitter, MD

BASICS DESCRIPTION General

• Heart transplant is the gold standard for the treatment of end-stage heart failure. Mechanical ventricular assist devices may be used as a “bridge to transplant.” • Indications for cardiac transplant include (1) – Severe, end stage disease that is refractory to surgical or medical therapy – NYHA Class III–IV despite maximum therapy – Compliant, motivated patient <70 years old – Heterotopic transplant is indicated for severe pulmonary hypertension and extreme donor/recipient size discrepancy. • Contraindications for cardiac transplant (1) – Fixed pulmonary vascular resistance (PVR) >5 Wood units – Active tobacco, alcohol, or drug use – Active neoplasm. Oncology consult regarding risk of recurrence for previous neoplasm – Major debilitating disease – Patient non-compilance – Relative contraindications: BMI>30, diabetes with end organ • Requires full cardiopulmonary bypass; cannula are inserted in the normal fashion (venous drainage from the IVC and the SVC and return via the aortic canula). Surgeons may use either a (2) – Biatrial technique (traditional): The recipient’s ventricles are removed, while leaving the right and left atrium and great vessels in place. The atrial cuffs of the transplanted heart are sewn onto the recipient’s. – Bicaval technique: The recipient’s ventricles and right atrium are excised while the left atrium and great vessels are left in place. The transplanted IVC and SVC are sewn to the free edges of the recipient’s SVC and IVC.

Position

Supine-careful attention to padding Incision

• Sternotomy • Prepare for possible groin cannulation, especially if previous sternotomy.

Approximate Time

• 6–8 hours. Repeat sternotomy patients require longer dissection time.

• Preparation of the recipient must be carefully timed with donor organ harvest; the recommended ischemic time is <4 hours.

EBL Expected

• Frequent postbypass coagulopathy requiring antifibrinolytic agents and transfusion of pRBCs, FFP, platelets, and cryoprecipitate. Coagulopathy generally occurs as a result of cardiopulmonary bypass, as well as preoperative anticoagulation and liver dysfunction. • Common surgical complications – Cardiac dysfunction of left, right, or both ventricles – Coagulopathy – Organ failure (kidneys, lungs) – Arrhythmias – Rejection

Hospital Stay

Typical ICU discharge by POD #3 but may have protracted hospital course. Special Equipment for Surgery

• Full cardiopulmonary bypass machine • Pacing capability • Availability of ventricular assist devices or intra-aortic balloon pumps

EPIDEMIOLOGY Incidence

• In the US, ∼2,000 heart transplants are performed each year. • The most frequent indications are idiopathic or ischemic cardiomyopathy.

Prevalence

Approximately 35% of patients listed for heart transplant will actually receive a transplant. Morbidity

• Early: Graft failure • Intermediate: Acute rejection or infection • Late: Allograft vasculopathy, lymphoproliferative disease, chronic rejection.

Mortality

• 1 year survival: 80–90% • Additional mortality: 4% per year. • Approximately 20–30% of patients on the transplant list will die from cardiac causes before a donor is found.

ANESTHETIC GOALS/GUIDING PRINCIPLES

Maintain and be prepared to aggressively support an adequate rhythm, preload, contractility, and afterload – Patients are exquisitely sensitive to changes in any of these parameters.

PREOPERATIVE ASSESSMENT SYMPTOMS

• NYHA Class III–IV symptoms of heart failure • Left-sided failure: Respiratory insufficiency, cyanosis, poor perfusion, orthopnea, paroxysmal nocturnal dyspnea, easy fatigue. • Right-sided failure: Peripheral edema, ascites, hepatomegaly.

History

• Assessment is often limited because of urgent surgery, but full transplant evaluation should be available. • Evaluate current symptoms, any changes in ischemic threshold or cardiac function, and NPO status.

Signs/Physical Exam

Evaluate volume status and signs of pulmonary vascular congestion • Lung auscultation • JVD • Peripheral edema • Poor perfusion or cyanosis

MEDICATIONS

• Beta-blockers • Diuretics • ACE inhibitors or angiotensin receptor blockers. • Digoxin • Inotropes • Anticoagulants

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes are often altered due to diuretics or excessive fluid retention. • Liver function tests may reflect hepatic venous congestion. • Coagulation studies • EKG: Dysrhythmias are common. • CXR to evaluate pulmonary venous congestion. • Echocardiography to assess right and left heart function, valvular abnormalities, and the presence of pericardial or pleural effusion. • Left and right heart catheterization. • Evaluation of pulmonary hypertension is critical.

CONCOMITANT ORGAN DYSFUNCTION

• Rule out existing organ dysfunction that would lead to mortality soon after transplant. • Reversible hepatic or renal dysfunction is often present.

• Endocrine and electrolyte abnormalities are common: Salt and water retention, glucose abnormalities, and hypokalemia due to diuretics.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Patients usually have elevated levels of catecholamines and are dependent on high preload (2). • Small doses of sedation may result in severe hemodynamic changes. • Patients are generally anxious but are very well informed about their care.

Special Concerns for Informed Consent

• Postoperative intubation and mechanical ventilation • Transfusion of blood products

Antibiotics/Common Organisms

• Patients will be immunosuppressed so meticulous attention to aseptic technique is vital. • Use blood products free of cytomegalovirus for patients lacking antibodies to this organism.

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia (2) • Timing coordinated with donor heart availability

Monitors

• Arterial line (preinduction) • Central venous catheter – Right IJ access may be utilized, although concern for access for future biopsies. • PA catheter – Insertion may be difficult in the dilated heart. Full insertion could possibly wait until after the donor heart implantation. • TEE • Large bore access • Repeat sternotomy: Consider placement of defibrillator pads and cross-matched and checked pRBCs in the room prior to sternotomy. Induction/Airway Management

• Concern for “full stomach,” preoxygenation, +/– rapid sequence induction with cricoid pressure, unexpected difficult airway equipment readily available. • Very sensitive to hemodynamic changes. Goal is to maintain heart rate, preload, contractility, and afterload. Continue inotropic support if the patient was reliant on it. • For induction, opioids and benzodiazepines are commonly used for hemodynamic stability. Some patients may tolerate low volatile agent.

Maintenance

• Standard concerns for cardiopulmonary bypass. • Insulin infusion will likely be necessary given the administration of steroids. • Weaning from bypass – The newly transplanted heart is preload dependent so special care should be given to maintain adequate filling pressures. – Particular attention should be paid to right ventricle function; it is the most common etiology of failure to wean.

Extubation/Emergence

• Patients remain intubated with sedation • Complications – Primary allograft failure secondary to inadequate myocardial protection, prolonged ischemic time, and reperfusion injury. – Right ventricle dysfunction Etiology may be secondary to residual pulmonary hypertension, air in the right coronary artery, valve insufficiency, or prolonged ischemic time. Increases in PVR can result from hypoxemia, hypercarbia, acidemia, and excessive tidal volumes and should be avoided. Treat with aggressive inotropic therapy and selective pulmonary vasodilators (inhaled nitric oxide, prostaglandins). – Coagulopathy, especially in patients with prior sternotomy.

POSTOPERATIVE CARE BED ACUITY

• Patients require cardiac surgical ICU care. • Cardiac issues – Maintain adequate oxygenation and ventilation – Meticulous optimization of hemodynamics. – Treat coagulopathy and hypothermia. • Transplant issues – Immunosuppressive regimen is initiated.

ANALGESIA

Standard postcardiac surgical pain management COMPLICATIONS

• Acute rejection during the first 6 months – Monitored by serial myocardial biopsies. • Pulmonary and systemic hypertension • Arrhythmias • Respiratory and renal failure. • Immunosuppression and subsequent risk of infection. Viral and fungal infections more common in long term.

PROGNOSIS

• Recipient risk factors for increased mortality include age, race, prior transplant, poor HLA matching, ventilator dependence, and size mismatching. • Donor risk factors for increased mortality are age, race, gender, and long ischemic time.

REFERENCES

1. Mehra M, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Patients—2006. J Heart Lung Transplant. 2006;25(9):1024–1042.

2. Fann JI, Reitz BA. Heart and lung transplantation. In Jaffe R, Samuels SI (Eds.), Anesthesiologist’s Manual of Surgical Procedures. 3rd edn. Lippincott Williams & Wilkins. Philadelphia, 2004:360–364. 3. Jacob S, Sellke F. Is bicaval orthotopic heart transplantation superior to the biatrial technique? Interact CardioVasc Thorac Surg. 2009;9(2):333–342.

ADDITIONAL READING

• Ramakrishna, et al. Anesthesia for heart transplantation. Ann Cardiac Anesth. 2009;12(1): 71–78.

See Also (Topic, Algorithm, Electronic Media Element) • Cardiopulmonary bypass • Congestive heart failure • Post-heart transplant

CODES ICD9

V42.1 Heart replaced by transplant ICD10 Z94.1 Heart transplant status

CLINICAL PEARLS

• Cardiac denervation occurs in heart transplant recipients – Stimuli do not produce normal responses of increased chronotropy and inotropy. – Instead, these patients respond to increased demand primarily by increases in stroke volume and, thus, are very preload dependent. – Vagolytic agents such as atropine will likely not affect heart rate. The heart continues to respond to direct acting agents such as epinephrine. • Anesthetic care of the donor follows general principles of brain-dead donor care – Maintain normovolemia, normothermia, normal to high preload, MAP 80–90 mm Hg (may

need vasopressors). – Avoid hypoxia and transfuse if oxygen supply is inadequate. – ARDS or neurogenic pulmonary edema may necessitate high levels of PEEP. – Central DI may lead to massive diuresis. • Right ventricle function is paramount – Preoperative assessment should demonstrate PVR <5 Woods units. – Postoperative management should optimize RV function. • Biatrial versus bicaval technique (3): – The bicaval technique may be associated with the following short-term benefits: Decreased atrial pressure, tricuspid valve regurgitation, and mortality, as well as quicker return to sinus rhythm – Long-term outcomes, however, do not appear to show a difference in survival at 1 and 3 years. – The bicaval technique is considered more technically demanding and may be associated with longer pump bypass and ischemic time.

HELLP SYNDROME Judith A. Turner, MD, PhD

BASICS DESCRIPTION

• HELLP is a syndrome of pregnancy characterized by Hemolysis, Elevated Liver enzymes, and Low platelets. • Diagnostic criteria for HELLP include thrombocytopenia (platelet count <100,000/L), AST and/or ALT >70 IU/L, and hemolysis with LDH >600 IU/L. • Twenty percent of patients with severe preeclampsia develop HELLP but the syndrome can occur without hypertension (HTN) and/or proteinuria. • Signs of HELLP usually manifest between 28 and 36 weeks gestation; however, ∼20% of patients will show initial manifestations at >48 hours after delivery. Resolution of symptoms usually occurs within 48 hours postpartum but can take up to 4 weeks. EPIDEMIOLOGY Incidence

• Overall deliveries: ∼0.6% • Preeclampsia develops in ∼10% of all pregnancies in the US.

Morbidity

• Maternal morbidity: Hepatic rupture, disseminated intravascular coagulation (DIC), seizure, pulmonary edema, renal failure • Fetal morbidity: Intrauterine growth restriction (IUGR), placental abruption, preterm delivery Mortality

Maternal and fetal mortality are associated with hepatic rupture and/or seizure. ETIOLOGY/RISK FACTORS

• Etiology unclear; HELLP is considered a severe form of preeclampsia. • Maternal risk factors for preeclampsia – Demographics: Age >40 years old, African-American ethnicity – Pregnancy associated: Nulliparity, multiple gestations, molar pregnancy – Comorbidities: HTN, renal disease, diabetes mellitus, factor V Leiden deficiency, antiphospholipid antibody • Paternal risk factors for preeclampsia: History of fathering a preeclamptic pregnancy with another woman; history of having a mother with preeclampsia during his gestation • HELLP recurrence is rare (∼3%).

PATHOPHYSIOLOGY

• Theories include abnormal implantation of trophoblastic tissue and imbalanced production of mediators. An atypical maternal immune response to embryonic trophoblasts can result in impaired invasion of trophoblastic cells into the uterine wall. This results in maladaptation of myometrial spiral arteries (high-resistance, and hence reduced uteroplacental flow). The hypoperfusion can cause placental hypoxia and the release of inflammatory cytokines into the maternal circulation with consequent endothelial dysfunction. • An imbalance of placental production of prostacyclin and thromboxane can result in systemic vasoconstriction and placental ischemia.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Control HTN (target SBP <160 mm Hg; DBP <110 mm Hg). • Seizure prophylaxis • Accelerate fetal lung maturity for gestational age <36 weeks with betamethasone if preterm delivery anticipated. • Evaluate for hemorrhage risk factors including thrombocytopenia, coagulopathy, and hepatic dysfunction. • Identify increased risk of hepatic rupture including thrombocytopenia, elevated liver enzymes, and right upper quadrant pain. • Prepare for urgent/emergent delivery. Indications for emergent delivery include nonreassuring fetal heart tones lasting >10 minutes, placental abruption, hepatic rupture, seizure, and/or end-organ damage.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Pulmonary: Dyspnea. • Hepatic: Abdominal pain, ascites, jaundice. • Hematologic: History of petechiae, mucosal bleeding, bruising. • Neurologic: Hyperexcitability, headaches, visual changes, seizure.

History

• Preeclampsia risk factors • Evaluate for other causes of elevated liver enzymes and/or RUQ pain: Hepatitis, cholecystitis, pancreatitis, appendicitis. • Rule out other causes of thrombocytopenia: Idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), systemic lupus erythematosus (SLE).

Signs/Physical Exam

• Airway: Pharyngolaryngeal edema • Pulmonary: Pulmonary edema, hypoxemia. • Cardiovascular: HTN, decreased central venous pressure (CVP). • Hematologic: Evidence of DIC (bruising, petechial, bleeding around catheter sites). • Renal: Oliguria.

• Hepatic: Hepatic edema. • Neurologic: Signs of intracranial hypertension (headache, vomiting, altered mental status).

TREATMENT HISTORY Preeclampsia therapy MEDICATIONS

• Antihypertensives • Seizure prophylaxis • Betamethasone

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Labs: Urinalysis for proteinuria, uric acid; complete blood count (platelets, hematocrit); complete metabolic panel (including Mg2+), coagulation studies, serum transaminates; Type and Cross. • Imaging studies – Abdominal ultrasound, CT, or MRI. Evaluate for hepatic infarction, hematoma, or rupture. – Chest X-ray. Evaluate for pulmonary edema. • Decreased glomerular filtration rate (GFR); increased proteinuria, uric acid, urine protein:creatinine ratio. CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular: Decreased CVP; increased peripheral vascular resistance, sensitivity to catecholamines; vasospasm, LV hypertrophy. • Pulmonary: Airway edema, pulmonary edema, increased risk of gastric aspiration. • Renal: Acute renal failure; decreased GFR, clearance of uric acid. • Hematologic: Hemoconcentration (increased blood viscosity), thrombocytopenia, coagulopathy. • Hepatic: Liver hematoma, hepatocellular damage, periportal hepatic necrosis. • CNS: Risk of cerebral edema, cerebral hemorrhage, alteration in cerebral autoregulation. • Placental: Uteroplacental insufficiency may lead to fetal hypoxia, IUGR. Increased risk of placental abruption, premature labor. CIRCUMSTANCES TO DELAY/CONDITIONS

• Delivery of the fetus and placenta is the only curative therapy. • Emergent delivery may be delayed in the absence of the following: Deterioration of clotting function (progression of thrombocytopenia and/or DIC); evidence of hepatic dysfunction, hematoma, and/or rupture; severe, refractory HTN >24 hours; renal failure; pulmonary edema, eclampsia or onset of neurologic deficits; placental abruption; nonreassuring fetal status. CLASSIFICATIONS

• HELLP syndrome • Preeclampsia

• Eclampsia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Seizure prophylaxis – Magnesium sulfate (first line): 4–6 g IV bolus over 15 minutes, followed by 1–2 g/hr. Therapeutic level ∼ 6–8 mEq/mL. – Phenytoin (second line): 10 mg/kg dose over 1 hour. – Diazepam (second line): 5–10 mg IV over 15 minutes, may be repeated every 15 minutes for a maximum dose of 30 mg. • BP control – Hydralazine (first line): 5–10 mg IV q15 minutes. – Labetalol (first line): 20 mg IV every 10 minutes up to a maximum dose of 300 mg. – Nifedipine (second line): 10 mg PO TID titrated to effect for a maximum dose of 120 mg daily. • Fetal lung maturity – Betamethasone given in divided doses to accelerate fetal lung development in anticipation of deliveries <36 weeks gestation. Special Concerns for Informed Consent

• Regional anesthesia and coagulopathy. • Blood products. Platelets rarely given for thrombocytopenia in the absence of hemorrhage. • Possible need for invasive monitoring.

INTRAOPERATIVE CARE Choice of Anesthesia

• Neuraxial anesthesia (spinal or epidural) is preferred. A careful evaluation of the risks versus benefits should be made in the setting of thrombocytopenia. Contraindications include patient refusal, elevated ICP, inability to cooperate, evidence of coagulopathy, or signs of local infection. Hypotension may accompany initiation of neuraxial anesthesia; patients with preeclampsia are often hypovolemic. • General anesthesia may be necessary in emergent deliveries (fetal distress, placental abruption, hepatic rupture, severe pulmonary edema, seizure, and/or end-organ dysfunction). Use is associated with increased risk of aspiration, transient neonatal depression, severe HTN, and cerebral hemorrhage. Monitors

• Pulse oximetry. Decrease in SpO2 in the setting of pulmonary edema, respiratory depression, and/or pulmonary aspiration. • BP monitoring. Consider invasive BP monitoring in the setting of refractory HTN (BP >180/120) or for frequent blood sampling.

• CVP. May be useful in determining volume status and for infusion of vasodilators. • Pulmonary arterial catheter rarely indicated. • Urinary output. Useful in evaluation of volume resuscitation and renal function. • Fetal heart tracing.

Induction/Airway Management

• Limit use of benzodiazepines and opioids prior to delivery; their use is associated with neonatal (respiratory/CNS) depression. • General anesthesia for emergent deliveries. A rapid sequence intubation with cricoid pressure should be used to minimize the risk of aspiration. Airway edema may increase difficulty of laryngoscopy. Avoid a hypertensive response to laryngoscopy by deepening of the anesthetic or using remifentanil and/or esmolol.

Maintenance

• General anesthesia can be maintained with a combination of volatile anesthetic and nitrous oxide. Volatile anesthetic at <0.5 MAC minimizes decreases in uterine tone. IV opioids and benzodiazepines can be given following clamping of the cord. • Magnesium sulfate prolongs the duration of nondepolarizing neuromuscular blockade.

Extubation/Emergence

• Extubation criteria include adequate oxygenation and ventilation as well as the ability to protect the airway. • Airway edema may necessitate reintubation. • Severe HTN and cerebral hemorrhage may accompany emergence and extubation.

POSTOPERATIVE CARE BED ACUITY

Consider ICU admission in patients with evidence of end-organ damage and/or need for mechanical ventilation. MEDICATIONS/LAB STUDIES/CONSULTS

• Continue antihypertensive medication until BP normalizes. • Continue seizure prophylaxis for 24 hours following last seizure. • Labs. Follow platelets, INR/PT, hepatic enzymes, BUN/Cr until values normalize.

COMPLICATIONS

Hepatic rupture or dysfunction; pulmonary edema, renal failure, thrombocytopenia, DIC, seizure, placental abruption, IUGR, preterm delivery, maternal or fetal death.

REFERENCES

1. Gasem T, Al Jama FE, Burshaid S, et al. Maternal and fetal outcome of pregnancy complicated by HELLP syndrome. J Matern Fetal Neonatal Med. 2009;22(12):1140–1143. 2. Practice guidelines for obstetric anesthesia: An updated report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Available at:

http://www.asahq.org/publicationsAndServices/OBguide.pdf. Accessed on January 08, 2011. Sibai BM, Stella CL. Diagnosis and management of atypical preeclampsia/eclampsia. Am J Obstet Gynecol. 2009;200:481.e1–481.e7. Katz L, de Amorim MMR, Figueiroa JN, et al. Postpartum dexamethasone for women with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome: A double-blind, placebo-controlled, randomized clinical trial. Am J Obstet Gynecol. 2008;198:283.e1–283.e8. 3. Turner J. Diagnosis and management of preeclampsia: An update. Int J of Women’s Health. 2010;2:1–11.

ADDITIONAL READING

• American College of Obstetricians and Gynecologists (ACOG) Practice bulletin: Diagnosis and management of preeclampsia and Eclampsia. Obstet Gynecol. 2002;99(1):159–167. See Also (Topic, Algorithm, Electronic Media Element)

• Pregnancy induced hypertension • Preeclampsia • Eclampsia

CODES ICD9 • 642.50 Severe pre-eclampsia, unspecified as to episode of care or not applicable • 642.51 Severe pre-eclampsia, delivered, with or without mention of antepartum condition • 642.52 Severe pre-eclampsia, delivered, with mention of postpartum complication ICD10 • O14.20 HELLP syndrome (HELLP), unspecified trimester • O14.22 HELLP syndrome (HELLP), second trimester • O14.23 HELLP syndrome (HELLP), third trimester

CLINICAL PEARLS

• Hepatic rupture is associated with an increased risk of maternal and fetal mortality. • Risk versus benefit of neuraxial analgesia/anesthesia must be carefully considered in the setting of severe thrombocytopenia. • Platelet transfusion is generally reserved only for cases of active or spontaneous bleeding.

HEMOGLOBIN

Michael P. Hofkamp, MD Russell K. McAllister, MD

BASICS DESCRIPTION

• Hemoglobin (Hb) is a molecular structure in red blood cells (RBCs) responsible for oxygen transport and acid/base balance. • Hb has an oxygen-binding capacity of 1.34 mL of oxygen per gram of Hb and provides a very efficient mechanism for carrying and transporting the gas. PHYSIOLOGY PRINCIPLES

• The Hb molecule comprises four noncovalently bound polypeptide chains (α-1, α-2, β-1, β-2). Each chain holds a heme group containing an iron atom responsible for binding oxygen. The hydrophobic portion of the heme is buried within the protein, while the hydrophilic “arms” are on the outer surface. This conformation results in a globular structure with four heme groups, capable of binding 4 oxygen molecules. • The primary function of Hb is to bind oxygen in pulmonary capillaries and then release it to the tissues. Hemoglobin exists in 4 physiologic forms: oxyhemoblobin (bound to oxygen) and deoxyhemoglobin (not bound to oxygen), as well as carbaminohemoglobin (bound to carbon dioxide; thus functions to transport CO2) and methemoglobin (reduced hemoglobin, cannot bind oxygen). • The oxyhemoglobin dissociation curve describes the relationship between PaO2 and the

oxygen saturation of Hb. A normal oxyhemoglobin dissociation curve is characterized by 50% of Hb being saturated with oxygen at a PaO2 of 26 mm Hb (P50 value).

• Cooperative binding – Oxygen binding to Fe2+ induces a conformational change in the Hb structure that facilitates oxygen binding to the other heme groups. – The shape of the oxyhemoglobin curve is sigmoid because as oxygen tensions increase it becomes exponentially easier for Hb to bind oxygen molecules. Conversely, as oxygen tension decreases, it becomes exponentially harder for Hb to bind oxygen. The splay of the curve on both the left and right sides reflects these exponential relationships. • A right-shifted oxyhemoglobin dissociation curve reflects a decreased affinity of Hb for oxygen, which facilitates unloading of oxygen to the tissues. Conditions that shift the oxyhemoglobin dissociation curve to the right: – Acidemia (increased [H+]–Bohr effect) – Increase in 2,3-diphosphoglycerate (chronic arterial hypoxemia or anemia), carbon dioxide, or temperature – Pregnancy (though it is reduced with preeclampsia) – Sickle cell disease

• A left shift in the oxyhemoglobin curve reflects an increased affinity of Hb for oxygen. This increased affinity is physiologically advantageous in situations where oxygen tension is low. Conditions that shift the oxyhemoglobin dissociation curve to the left: – Alkalemia – Increased levels of fetal Hb (P50 = 19 mm Hg) and fetal circulation where HbF avidly

binds oxygen in the uterus to be unloaded in the very low oxygen tensions of the fetal tissues. – Methemoglobinemia or carboxyhemoglobinemia (see details below) – High concentrations of transfused blood that has been stored. • Emerging evidence suggests that Hb is involved in the transport of nitric oxide, a vasodilator, to the tissues. • Hb accomplishes its buffering action through exposed histidine residues on the polypeptide chains. • The viscosity of RBCs contributes to resistance. Resistance = [(viscosity × length)/diameter4]. Because pressure = Flow × resistance, viscosity is directly related to pressure. • Erythropoietin is a hormone produced in the kidneys and liver that promotes synthesis of RBCs.

ANATOMY

• Adult Hb normally consists of HbA, HbA2, and HbF. – 95–98% of adult hemoglobin is HbA. – 2–3% of adult hemoglobin is HbA2. – Less than 2% of adult hemoglobin is HbF.

DISEASE/PATHOPHYSIOLOGY

• Anemia: “not enough” Hb – Causes can be categorized as blood loss, decreased production of RBCs, and/or increased destruction of RBCs. – Iron deficiency anemia is common in menstruating females and can be treated with dietary supplementation of iron. – Pernicious anemia is caused by a lack of secretion of gastric intrinsic factor leading to low absorption of vitamin B12. – The decrease in blood viscosity can result in decreases in blood pressure. • Polycythemia: An excess of Hb – Polycythemia vera is a hereditary cause – Acquired causes result from a compensatory response to chronic hypoxia. They include COPD, sleep apnea, congenital heart disease. Athletes seeking a competitive advantage have been reported to use erythropoietin to artificially increase RBC mass. – Extreme levels of polycythemia can increase blood viscosity and cause thrombosis resulting in cerebrovascular accidents or cardiac events; impairs ideal “rheology” through blood vessels. • Sickle cell disease – HbS is the result of a mutation in the coding gene for HbA (substitution of a valine instead

of glutamic acid at the 6th position of the β-subunit); this creates a new hydrophobic spot within the normally hydrophilic outer arm. In hypoxic environments, deoxygenated Hb aggregates with hydrophobic spots on other deoxygenated Hb molecules, resulting in polymerization. Homozygous patients are severely affected, while heterozygous patients are carriers. – Pathophysiology. HbS is less resilient than HbA with a RBC lifespan of 10–20 days instead of the normal 120 days with resulting anemia. Sickled RBCs tend to clump together leading to decreased organ blood flow and even infarction. Increased production of HbF is a compensatory response. – Management. Optimize volume status (avoid dehydration); exchange transfusions when indicated; adequate pain control; avoid factors that favor sickling such as hypoxemia, hypothermia, and stasis (tourniquets) • Thalassemias – α. Caused by a defect in the α-1 or α-2 gene. The severity of disease is dependent on the number of affected genes. – β. Caused by a defect in genes coding for β-globulin. The minor variant exhibits a hypochromic, microcytic anemia. The intermediate variant has an increase in HbF and a left shift on the oxyhemoglobin dissociation curve. The major variant (Cooley’s anemia) can manifest with significant problems in infancy that include overgrowth of the maxilla, CHF, pericarditis, SVT, cor pulmonale, and hepatomegaly. Treatment includes supportive care and transfusion to keep Hb above 9 g/dL. • HbC – Glutamic acid is replaced by lysine at the 6th position on the β-globulin chain. – Autosomal recessive disease with heterozygous asymptomatic carriers; in contrast, homozygous patients have a mild hemolytic anemia. • HbE – Similar to HbC, glutamic acid is replaced by lysine, but at the 26th position of the βglobulin chain. – Similar to HbC, HbE is also autosomal recessive with heterozygotes as asymptomatic carriers and homozygotes displaying a mild hemolytic anemia. • HbA1c. Hb reacts with glucose molecules to form glycosylated Hb. The higher the glucose concentration the Hb is exposed to, the higher the number of glycosylated molecules. Therefore, HbA1c is a good measure of the glucose level over the previous several weeks and is used to monitor glycemic control in diabetics. • Methemoglobinemia – The iron in Hb can be oxidized to Fe3+ (from normal Fe2+). Oxidized Hb is unable to bind oxygen and impairs oxygen delivery to the tissues. – Methemoglobin absorbs light equally at the two wavelengths used in pulse oximetry, giving a ratio of 1. This ratio is read by the conventional pulse oximeter to be a saturation of 85%. – Methemoglobinemia can be caused by administration of oxidizing substances, such as prilocaine (EMLA cream), procaine (Hurricaine spray™), dapsone, nitrates, and aniline dyes. – Deficiencies in NADH methemoglobin reductase (G6PD deficiency, pyruvate kinase

deficiency) decrease the ability to convert methemoglobin to normal Hb. – Treatment of methemoglobinemia is with methylene blue 1–2 mg/kg given as a slow IV push over 5 minutes (contraindicated in G6PD deficiency due to resulting hemolysis). • Carboxyhemoglobinemia – Occurs most commonly as a result of smoke exposure (chronic smokers, structure fire victims) or from improper ventilation in areas with car exhaust fumes. – Carbon monoxide (CO) has a 300-fold greater affinity for Hb compared to oxygen. – Hb saturated with CO cannot deliver oxygen to the tissues. – A conventional pulse oximeter will not detect the abnormal oxygen saturation in CO poisoning. – Hyperbaric oxygen can overcome Hb’s preferential binding of CO in clinically significant cases.

PERIOPERATIVE RELEVANCE

• Adequate oxygenation of tissues is dependent on appropriate levels of Hb saturated with oxygen. • Blood transfusion – Hb can be transfused in the form of packed RBCs (most common) and whole blood. – The only indication for Hb transfusion is to increase the oxygen-carrying capacity of blood. Unlike crystalloid and colloid solutions, transfusion of packed RBCs is not an appropriate volume expander. However, because it can increase blood viscosity (and hence resistance to flow), it can increase blood pressure. • Transfusion “triggers”: – Evidence of an existing or impending deficiency in oxygen delivery to the tissues – Assessment of adequate oxygenation of tissues can be challenging and the entire clinical picture needs to be taken into account. Review of vital signs, crystalloid and colloid infusion, blood loss, acid/base status, presence of lactic acidosis, Hb/Hct, and possibly mixed venous oxygen saturation can help guide the decision-making process. – Based on viscosity and cardiac pump performance, the Hb level that maximizes oxygen delivery to the tissues has been shown to be 10 g/dL. However, there are no absolute “triggers” for Hb transfusion. Patients at risk for cardiac disease are generally maintained at a Hb of 10 g/dL or greater. Otherwise healthy patients frequently tolerate a Hb as low as 6 g/dL. • Sickle cell disease – Mostly supportive care involving optimization of volume status, oxygenation, and temperature to avoid a vaso-occlusive crisis. – Transfusion of RBCs is indicated when signs or symptoms of anemia are present (e.g., dyspnea, high output cardiac failure, and postural hypotension). • Ischemic optic neuropathy – Anemia is thought to be a risk factor in this rare perioperative event that involves ischemia of the optic nerve and vision loss. • Jehovah’s witnesses – Patients will often refuse transfusion of blood products, even under life-threatening circumstances. – Jehovah’s witness patients have been reported to survive with Hb levels as low as 3 g/dL.

– Strategies to minimize blood loss. Some Jehovah’s witness patients will allow return of autologous blood that has been salvaged intraoperatively. Individual patients will sometimes insist that a complete circuit be connected between them and the salvaging apparatus. Isovolemic hemodilution involves collecting whole blood from a patient in the immediate perioperative period and replacing that volume with crystalloid or colloid. It does not decrease the volume of blood loss (unlike controlled hypotension), but instead decreases the mass of red blood cells that are lost (the blood that is lost has a lower hematocrit). However, some Jehovah’s witnesses will not accept autologous blood collected using this technique. • Newer pulse oximeters can monitor Hb levels and variant forms of Hb continuously. • Research into oxygen-carrying Hb substitutes, such as perfluorocarbons continues, but has not yet produced a viable alternative to RBC transfusion.

Pregnancy Considerations

Physiologic anemia of pregnancy. Plasma volume increases relative to red cell mass and results in a dilutional anemia. A “normal” Hb in pregnancy is 11 g/dL. To compensate, cardiac output increases and there is a right shift of the oxyhemoglobin dissociation curve. Pediatric Considerations

The increase in oxygenation that occurs with normal breathing after birth, causes a sharp rise in tissue O2 level; this causes a negative feedback on erythropoietin production with resultant

anemia. Normal Hb levels decrease for 6–8 weeks before production of erythropoietin resumes. This anemia rarely requires intervention. Geriatric Considerations

Elderly patients have a higher incidence of cardiac risk factors that favor maintaining an Hb level above 10 g/dL. EQUATIONS

Calculation of arterial content of blood: CaO2 = (SaO2 × Hb × 1.34) + 0.003(PaO2); where

CaO2 is the arterial content of oxygen in blood, SaO2 is the oxygen saturation, and PaO2 is the

partial pressure of oxygen in blood.

REFERENCES

1. Firth PG. Anesthesia and hemoglobinopathies. Anesthesia Clin. 2009;27(2):321–326. 2. Kamat V. Pulse oximetry. Indian J Anaesth. 2002;46(4):261–268.

ADDITIONAL READING

• www.umass.edu/molvis/tutorials/hemoglobin/sickle.htm See Also (Topic, Algorithm, Electronic Media Element) • Methemoglobinemia • Oxygen carrying capacity

• Sickle cell disease • Hemolytic anemia

CLINICAL PEARLS

• Increasing oxygen-carrying capacity is the only indication for transfusion of RBCs. • Hydroxyurea increases the amount of fetal Hb in sickle cell patients. • Recombinant erythropoietin (EpogenTM, ProcritTM) can be administered to patients with chronic anemia with the goal to avoid transfusion. The Food and Drug Administration (FDA) has issued a “Black Box Warning” against erythropoietin administration to patients to a target Hb >12 g/dL as it has been associated with an increased incidence of thromboembolic events. The FDA recommends using the lowest dose possible to gradually raise the Hb to the lowest level sufficient to avoid transfusion.

HEMOLYTIC ANEMIA Malina M. Varner, MD Kathleen S. Donahue, DO, FAAP

BASICS DESCRIPTION

• Hemolytic anemia describes a low red blood cell (RBC) count that results from lysis of erythrocytes. • Over 200 causes exist and are either (1): – Congenital: Hemoglobinopathies, enzyme defects, and cell membrane defects – Acquired: Injury to the cells increases splenic sequestration and clearance by the immune system; or abnormal immune complexes form and attach to the RBC (signals for hemolysis). • Perioperative management depends on the etiology. The preoperative evaluation, optimization, intraoperative management, and postoperative care should be appropriately tailored. EPIDEMIOLOGY Incidence

Accounts for 5% of all causes of anemia (1) Morbidity

• Depends on the underlying etiology of anemia • Patients can develop leg ulcers, folate deficiency, hemosiderosis, and gallstones • Can precipitate angina and heart failure in patients with underlying cardiovascular disease

Mortality

Overall incidence of death is rare ETIOLOGY/RISK FACTORS

• Congenital (commonly diagnosed in childhood) (1): – Hemoglobinopathies: Sickle cell, thalassemia – Enzyme defects: G6PD deficiency – Cell membrane defects: Hereditary spherocytosis • Acquired – Mechanical injuries: Artificial valves, cardiopulmonary bypass (CPB), preeclampsia – Hypersplenism – Burns – Drugs that impose oxidative stress on the erythrocyte (nitrates, methylene blue, methyldopa, ribavirin) – Infectious: Malaria, Escherichia coli 0157:H1, C. perfringens

– Autoimmune hemolytic anemia (AIHA) – Transfusion-related

PATHOPHYSIOLOGY

• Inherited hemolytic anemias. Lysis is the final outcome to a variety of deficits within the erythrocyte: – Hemoglobinopathies. In sickle cell disease, the average red cell half-life is decreased. This is due to the following: Mechanical cell membrane damage while traversing through capillaries; injury from reactive oxygen species; and the formation of antibodies to erythrocyte clusters seen during sickling (2). – Enzymes. G6PD deficiency results in the inability to produce glutathione, which is responsible for reducing hemoglobin during oxidative stress. The oxidized hemoglobin precipitates in the RBC and forms Heinz bodies that are “flagged” and removed by the spleen (3). – Cell membrane structure. Hereditary spherocytosis and its abnormal sphere shape result in splenic sequestration and hemolysis, thereby reducing its lifespan. • Acquired hemolytic anemias. – Mechanical injury: Prosthetic heart valves, CPB, eclampsia, hemolytic uremic syndrome (HUS), disseminated intravascular coagulopathy (DIC) – Exposure – Disease (malaria invades the erythrocyte and causes destruction) – Drugs may cause immune-mediated hemolysis • Erythrocyte lysis causes release of hemoglobin molecules as well as lactate dehydrogenase (LDH).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Although hemolytic anemia comprises only 5% of all causes of anemia, it should be considered and ruled out when anemia is present. When diagnosed, the underlying etiology should be discerned and treatment and management should be tailored accordingly. • A hematology consult prior to surgical intervention should be considered in patients with rare etiologies.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Anemia: Angina, dyspnea, and weakness due to decreased oxygen carrying capacity (2). • Right upper quadrant (RUQ) pain due to gallstone formation from excessive bilirubin.

History

• Often suspected after an incidental laboratory finding • Known family history if hereditary

Signs/Physical Exam

• Generalized pallor (1) • Pale conjunctiva

• Tachycardia, tachypnea, and hypotension • Splenomegaly, RUQ tenderness • Leg ulcer • Acute chest syndrome (sickle cell disease)

TREATMENT HISTORY

• Depends on the cause • Sickle cell disease: Blood transfusions, splenectomy • Autoimmune: Corticosteroids, plasmapheresis • Drug induced: Discontinue possible medications as precipitating factors

MEDICATIONS

Depends on the etiology but can include folic acid, iron replacement, and corticosteroids (1).

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC: Low hemoglobin levels; normal MCV. Increased erythrocyte levels may be associated with MCV elevation (1). • Haptoglobin levels are decreased due to binding with free hemoglobin. • Reticulocyte counts are increased and reflect the bone marrow’s attempt to restore erythrocyte levels. • LDH levels are elevated due to release into the circulation when erythrocytes are destroyed. • Bilirubin: Indirect levels are often elevated due to an increased load that “backs up” before being conjugated by the liver. • Peripheral smears may demonstrate the etiology of hereditary causes. • WBC and platelet counts may provide information about underlying malignancy or hematologic disease. • Type and screen for operative procedures where blood loss may occur. • Type and cross for patients with transfusion dependent anemia or patients with difficult to cross blood due to rare antibodies (always consider in patients with a history of mulitple transfusions). • CXR if there is concern for hemodynamic compromise or acute chest syndrome (2).

CONCOMITANT ORGAN DYSFUNCTION

• Splenic infarct in sickle cell • Myocardial stress due to poor oxygen supply • Renal failure

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Acute cardiovascular decompensation • Acute chest syndrome • Sepsis if underlying infectious cause • Need for exchange transfusion or plasmapheresis

CLASSIFICATIONS

• Congenital • Acquired

TREATMENT PREOPERATIVE PREPARATION Premedications

• Avoid oxidative stress (hemolytic crisis) from anxiety and pain by appropriately titrating benzodiazepines and fentanyl in patients with known G6PD deficiency (3). • Exchange transfusions and appropriate hydration may be performed in sickle cell patients. There is no general consensus regarding preoperative hemoglobin levels, but some clinicians transfuse to maintain a hemoglobin level of 10 g/dL (2). • For AIHA, controversy exists whether pretreatment with high-dose corticosteroids is beneficial; however, these patients may be on chronic immunosuppression. Consider administering a stress dose of steroids, if appropriate (1).

Special Concerns for Informed Consent

Patients should be informed about the possible need for blood transfusion. INTRAOPERATIVE CARE Choice of Anesthesia

• Based primarily on the surgical procedure and patient comorbidities. • Avoid medication that may cause hemolysis under oxidative stress (3). – Acetaminophen – Antibiotics including penicillin, nitrofurans, isoniazid, and chloramphenicol – Sulfa derivatives such as furosemide – Antimalarial drugs – Miscellaneous including methylene blue, quinidine, vitamin K analogs, probenecid, and possibly nitroprusside. • Regional and/or neuraxial anesthesia may be considered to optimize postoperative pain control and decrease stress. Significant sedation for these procedures may cause hypoxia and hypercarbia that can precipitate sickling in susceptible patients (2).

Monitors

• Standard ASA monitors • Additional invasive monitoring is primarily dictated by the type and length of the surgery as well as comorbid conditions. The necessity for frequent labwork should be considered. • Foley catheters may be helpful as hemoglobinuria may be visually diagnosed.

Induction/Airway Management

• Depends on the surgical procedure • Avoid hypoxia and hypotension that could provoke sickling or a hemolytic crisis in G6PD deficiency.

Maintenance

• G6PD deficiency. Avoid oxidative stressors such as hypoxia, hypovolemia, and hypothermia as well as select drugs. The use of benzodiazepines, fentanyl, propofol, and ketamine has not been shown to cause a hemolytic crisis (3). • Sickle cell crises may be avoided with aggressive hydration, avoidance of hypoxia, hypothermia, and acidosis. • Acute hemolytic transfusion reactions are manifest by hypotension, tachycardia, rash, hyperthermia, and hematuria (1). – Immediately stop the transfusion – Begin resuscitative measures in the form of hemodynamic support and aggressive hydration and diuresis (to combat acute renal failure, ARF) – Send additional donor and recipient blood to be retested in the laboratory.

Extubation/Emergence

Careful attention should be paid to adequate pain control and oxygenation to avoid stress that could trigger an acute hemolytic crisis.

POSTOPERATIVE CARE BED ACUITY

Determination based primarily on the type of surgery MEDICATIONS/LAB STUDIES/CONSULTS • Hematology consult • Postoperative CBC should be followed

COMPLICATIONS

• Hemodynamic compromise due to acute hemolysis and decreased oxygen carrying capacity • ARF precipitated by elevated free hemoglobin

REFERENCES

1. Lucio L.Hemolytic Anemias and Anemia Due to Acute Blood Loss (Chapter 101). In: Fauci AS, Braunwald E, Kasper DL, et al. (eds.). Harrison’s Principles of Internal Medicine, 17th ed. McGraw-Hill Professional. New York, New York; 2008.

2. irth PG, McMillan KN, Haberkern CM, et al. A survey of perioperative management of sickle cell disease in North America. Paediatr Anaesth. 2011;21(1):43–49. 3. Elyassi AR, Rowshan HH. Perioperative management of the glucose-6-phosphate dehydrogenase deficient patient: A review of literature. Anesth Prog. 2009;56(3):86–91. See Also (Topic, Algorithm, Electronic Media Element) • Sickle cell disease • Anemia • Cardiopulmonary bypass • Preeclampsia

CODES ICD9

• 282.0 Hereditary spherocytosis • 283.9 Acquired hemolytic anemia, unspecified ICD10

• D58.0 Hereditary spherocytosis • D59.9 Acquired hemolytic anemia, unspecified

CLINICAL PEARLS

• Acute causes of hemolytic anemia in the operating room are likely related to blood transfusion or medication administration. The inciting agent should be discontinued immediately and supportive measures provided.

HEMOPHILIA Neesa Patel, MD

BASICS DESCRIPTION

• Hemophilia is an inherited disorder of hemostasis characterized by a deficiency in clotting factors. – Hemophilia A: Deficiency of factor VIII (FVIII) coagulant protein; X-linked recessive inheritance. – Hemophilia B: (Christmas disease) Deficiency in factor IX (FIX) coagulant protein; Xlinked recessive inheritance – Hemophilia C: Deficiency of factor XI (FXI); autosomal-recessive inheritance (rare) • Hemophiliacs pose the risk of increased surgical and postoperative bleeding; their care should be tailored and coordinated between the anesthesia provider, surgeon, and hematologist. EPIDEMIOLOGY Incidence

• Hemophilia A: 1 in 10,000 male births. Severe form is found in 7 out of 10 with the disease • Hemophilia B: 1 in 50,000 male births • The ratio of hemophilia A to B is 9:1 • Hemophilia C: Very rare; seen more commonly in Ashkenazi Jews

Prevalence

In the US: ∼20,000 people Morbidity

Intracranial hemorrhage and complications associated with blood transfusions Mortality

Overall mortality is twice that of a healthy male ETIOLOGY/RISK FACTORS

• Results from large inversions, insertions, deletions, or point mutations of FVIII or FIX genes; located on the long arm of chromosome X. • The disease is typically inherited, but acquired disease is also a possibility.

PATHOPHYSIOLOGY

• FVIII and FIX circulate in the plasma in an inactive form. When activated, these two factors cooperate to cleave and activate FX (controls the conversion of fibrinogen to fibrin). • Lack of either of these factors significantly alters clot formation resulting in clinical

bleeding. Factor activity is described as a percentage; for example, normal patients have 100% activity, whereas severe disease is defined as <1% activity. • The hallmark of hemophilia is hemorrhage into joints that causes long-term inflammation and deterioration of the joint. Human synovial cells in joints synthesize high levels of tissue factor pathway inhibitor, resulting in a higher degree of FXa inhibition, mainly for moderate-to-severe forms. There is no excessive bleeding after minor cuts or abrasions for mild-to-moderate disease. • Acquired hemophilia is the development of FVIII inhibitors (autoantibodies) in persons without a history of FVIII deficiency (1). Associated conditions include idiopathic, collagen vascular disease, drug reaction (e.g., to penicillin), and lymphoproliferative malignancies.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients pose an increased risk of bleeding and hemorrhage perioperatively. Hematology consultation should be considered to aid with perioperative management. • In elective cases, specific coagulant factor replacement (mild, moderate, severe) or 1deamino-8-d-arginine vasopressin (DDAVP) (mild disease) are typically administered. Levels of the deficient coagulation factor should be assayed 48 hours before surgery and restored to 40% of normal before surgery (higher for major surgeries and orthopedics). • For emergent surgery, consider fresh frozen plasma (FFP) (mild-to-moderate disease), DDAVP, concentrate replacement, and FVIIa (refractory bleeding).

PREOPERATIVE ASSESSMENT SYMPTOMS

Hematuria, GI bleeds, easy bruising History

• Bleeding (seldomly from small cuts or venipuncture). Patients with severe disease commonly report a history of intraarticular and intramuscular bleed. • The majority of patients are known to have hemophilia because of family history.

Signs/Physical Exam

Joint deformities, large subcutaneous, and soft-tissue hematomas. TREATMENT HISTORY

• Multiple transfusions • Hospital admissions for bleeding post-trauma

MEDICATIONS

Factor concentrate. Severe hemophiliacs are commonly placed on prophylactic IV infusions for reduction in arthropathy and to prevent bleeding (2).

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• PTT values are prolonged, whereas `PT’ is typically normal.

• Factor levels VIII or IX • Preoperative screening for factor inhibitors (IgG antibodies) should be measured in severe disease states (FVIII antibodies seen in ∼25% and FIX in ∼3–5%) (3). Inhibitors can result in a diminished, inhibitory, or anaphylactic response to concentrates.

CONCOMITANT ORGAN DYSFUNCTION

• Synovitis and joint destruction in patients with hemarthroses. This results in permanent deformities, misalignment, loss of mobility, and extremities of unequal lengths. • Transfusion-related infections have markedly reduced with improvements in donor screening, virucidal techniques, and the development of recombinant products. • Commonly associated with von Willebrand’s disease. Women may be “symptomatic carriers” of hemophilia. FVIII and von Willebrand factor (VWF) levels tend to rise during pregnancy and then often fall abruptly following delivery. Coagulation parameters should be obtained in the 3rd trimester to evaluate for the safety of epidural placement (4).

CIRCUMSTANCES TO DELAY/CONDITIONS

Elective surgery should be delayed for proper evaluation of activity levels and treatment with concentrates, as appropriate. CLASSIFICATIONS

• Severe disease: <1% normal factor activity (<0.01 IU/mL). Spontaneous bleeding may occur, classically hemoarthrosis. • Moderate disease: 1–5% normal factor activity (0.01–0.05 IU/mL). • Mild disease: 5–40% normal factor activity (>0.05 to <0.40 IU/mL).

TREATMENT PREOPERATIVE PREPARATION Premedications

• Desmopressin (DDAVP)—may administer to control or prevent bleeding in mild-to-moderate hemophilia A. DDAVP is a synthetic analogue of vasopressin (antidiuretic hormone) that lacks pressor activity; It increases circulating FVIII levels 2–4 times above baseline via release from endothelial storage sites; in those with FVIII levels 9% of normal, it can increase circulating FVIII levels 4–6 times above baseline (5). Dosage: 0.3 μg/kg IV over 15– 30 minutes; should be administered 30 minutes prior to scheduled procedure while monitoring BP and pulse. • Recombinant FVIII and FIX (moderate and severe disease) should be administered in consultation with a hematologist. For every 1 U/kg of concentrate that is administered, activity levels rise by ∼1–2%. – In elective surgery, the goal is to attain 40% activity. In severe disease, an initial dose of 20 U/kg can be given within 1 hour of surgery, followed by 1.5 U/kg/hour of FVIII or 2 U/kg/hour of FIX. – For major surgical procedures, factor levels should be between 60% and 100% prior to surgery and maintained at 30–50% until the wound has healed (typically for 10–14 days)

(3). – For orthopedic procedures, activity levels of 80–100% are suggested and should be maintained at 30% for several days after the procedure. • Presence of inhibitors to FVIII and FIX may make therapy with concentrates not an option. Instead, recombinant FVIIa may be given as an initial IV bolus of 90–120 μg/kg over 2–5 minutes and redosed every 2 hours until hemostasis is attained (6).

Special Concerns for Informed Consent

Jehovah’s witness: Consent must be detailed for any plasma-derived clotting factor replacement. INTRAOPERATIVE CARE Choice of Anesthesia

• General or sedation depending on the surgical procedure • Neuroaxial blocks are contraindicated given the risk of epidural hematoma. • Peripheral nerve blocks (PNBs) may be safely performed in a hemophiliac patient, provided that FVIII and IX activity levels are appropriate (7). Consider ultrasound assisted to decrease the risk of tissue trauma or vessel puncture.

Monitors

• Dependent on surgery. High-risk or prolonged procedure should consider invasive monitors. • Arterial line may be beneficial in patients for serial PTT and factor level evaluation in severe hemophiliacs. • A second large bore IV line should be placed for infusion of factors.

Induction/Airway Management

Concerns for bleeding from airway trauma are decreased if factor replacement has been initiated. Maintenance

Intraoperative bleeding poses the greatest risk despite optimizing preoperatively. Be prepared to administer FFP, FVIIa, or increase the infusion rate of factor concentrate. Extubation/Emergence

Standard criteria apply depending on the patient’s medical history, airway concerns, and type of surgery.

POSTOPERATIVE CARE BED ACUITY

• Depends on the risk of postoperative bleeding, type of surgery, and severity of disease • Depending on the institution, factor concentrate infusion may not be administered on the floor.

MEDICATIONS/LAB STUDIES/CONSULTS

• Ongoing consultation with hematologist • Labs: Factor levels, inhibitors, and PTT levels should be checked postoperatively and as needed. • Additional factor replacement should be guided by the activity of clotting factors for about 6–10 days postoperatively (depending on the surgical procedure) (8), and in conjunction with a hematologist.

COMPLICATIONS

Ongoing surgical bleeding beyond the initial postoperative period is a concern.

REFERENCES

1. Bitting RL, Bent S, Li Y, Kohlwes J. The prognosis and treatment of acquired hemophilia: A systematic review and meta-analysis. Blood Coagul Fibrinolysis. 2009;20(7):517–523. 2. erntorp E. Consensus perspectives on prophylactic therapy for haemophilia: Summary statement. Haemophilia. 2003;9(Suppl 1):1–4. 3. Martlew VJ. Peri-operative management of patients with coagulation disorders. Br J Anaesth. 2000;85(3):446–455. 4. Varughese J, Cohen AJ. Experience with epidural anaesthesia in pregnant women with von Willebrand disease. Haemophilia. 2007;13(6):730–733. 5. Mannucci PM, Ruggeri ZM, Pareti FI, et al. 1-Deamino-8-d-arginine vasopressin: A new pharmacological approach to the management of haemophilia and von Willebrands’ diseases. Lancet. 1977;1(8017):869–872. 6. Shapiro AD, Gilchrist GS, Hoots WK, et al. Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in haemophilia patients with inhibitors undergoing surgery. Thromb Haemost. 1998;80(5):773–778. 7. Sripada R, Reyes JJ, Sun R. Peripheral nerve blocks for intraoperative management in patients with hemophilia A. J Clin Anesth. 2009;21(2):120–123. 8. Brettler DB, Levine PH. Factor concentrates for treatment of hemophilia: Which one to choose? Blood. 1989;73:2067. 9. Ramsahoye BH, Dasani H, Pearson JF. Obstetric management in von Willebrand disease: A report of 24 pregnancies and a review of the literature. Haemophilia. 1995;1:140–144. 10. Logan AC, Goodnough LT. Recombinant factor VIIa: An assessment of evidence regarding its efficacy and safety in the off-label setting. Hematology Am Soc Hematol Educ Program. 2010;2010:153–159. See Also (Topic, Algorithm, Electronic Media Element) • von Willebrand’s disease • Partial thromboplastin time

CODES ICD9

• 286.0 Congenital factor VIII disorder • 286.1 Congenital factor IX disorder ICD10

• D66 Hereditary factor VIII deficiency • D67 Hereditary factor IX deficiency

CLINICAL PEARLS

• Early consultation with a hematologist is critical to evaluate the extent of disease and treatment options. • If a patient has had a history of multiple factor replacements in the past, there is an increased likelihood that inhibitors may have formed. • Obstetrical literature suggests maintaining FVIII levels to more than 30% to minimize the risk of bleeding after delivery (9). • Recombinant factor VIIa is FDA approved to treat bleeding secondary to hemophilia (10). When administered in pharmacological doses (~1000 times greater than normal circulating levels), rFVIIa improves the coagulation process at the site of injury by: – Directly (without forming a complex with tissue factor [TF]) activating factor X on the activated platelets at the site of injury, and thus bypassing the need for factors VIII and IX. – Boosting the TF-dependent pathways • Cardiopulmonary bypass. Preoperative preparation includes attaining a factor activity level of 100%. During bypass, it is not necessary to administer an infusion to counteract the dilutional effect of the pump circuit. A repeat bolus of factor concentrate is given post bypass and prior to wound closure followed by factor infusion. It is safe to administer standard heparinization doses during cardiac bypass as well as protamine reversal.

HEPARIN-INDUCED THROMBOCYTOPENIA (HIT) A. Katharina Beckmann, MD James D. Boone, MD

BASICS DESCRIPTION

• Describes a drug-induced thrombocytopenia after exposure to any dose or type of heparin • Two types of heparin-induced thrombocytopenia (HIT) exist: – Type I most likely has a nonimmune mechanism. Heparin causes mild platelet aggregation, especially in patients with activated platelets. This results in increased platelet sequestration in the spleen, leading to thrombocytopenia. – Type II is an autoimmune complication after heparin exposure. Unlike other drug-induced thrombocytopenias, HIT does not cause bleeding. Instead, it causes thrombosis and carries an increased risk for thromboembolic complications. For the purpose of this chapter, HIT will refer to type II. EPIDEMIOLOGY Incidence

• Type I: 1–4% following exposure to unfractionated heparin and in <1% of patients treated with low molecular weight heparin (LMWH). • Type II: 0.5–5% after exposure to unfractionated heparin for more than 4 days.

Morbidity

In association with thrombosis 9–11% Mortality

• Overall 1% • If thrombosis develops: 8–20% (despite treatment)

ETIOLOGY/RISK FACTORS

• Longer duration of heparin therapy (>4 days) • Use of unfractionated heparin rather than LMWH • Bovine in origin rather than porcine • Surgical rather than medical patients; highest risk after cardiac, orthopedic, and neurosurgical procedures • Female gender • Rare in pediatric, obstetric, and patients receiving hemodialysis • Malignancy • Severe thrombocytopenia • High heparin-PF4 antibody titer

PHYSIOLOGY/PATHOPHYSIOLOGY

• Heparin is a highly sulfated and negatively charged glycosaminoglycan that has a high affinity for platelet factor 4 (PF4). – PF4 is highly positively charged. It is found in the alpha-granules of platelets and exists in the plasma in low levels (following platelet activation, the PF4 plasma concentration rises). – PF4 binds to heparin, forming a heparin-PF4-complex. A conformational change in PF4 occurs, that leads to the exposure of new epitopes. These epitopes act as immunogens, and stimulate the production of IgG antibodies. – The heparin-PF4 complex binds to platelets via heparin binding sites. – When IgG binds to this complex, platelets become activated and further release PF4. This leads to Platelet consumption Thrombocytopenia Thrombin release Tissue factor activation; sets off the cascade and leads to a prothrombotic state. • Since LMWH has a shorter molecular length than unfractionated heparin, it binds weakly to PF4 and is less likely to cause HIT.

PREVENTATIVE MEASURES

• Heparin avoidance • Early recognition and treatment to avoid complications

DIAGNOSIS • Type I: – Mild thrombocytopenia with an early-onset (usually within 2 days) – The platelet count is rarely <80 × 109/L – Spontaneous resolution within a few days even if heparin is continued. – Patients are usually asymptomatic and have no thrombosis. • Type II. Diagnosis should initially be made on a clinical basis: Development of thrombocytopenia while on heparin, exclusion of other causes of thrombocytopenia, and resolution of thrombocytopenia after cessation of heparin administration. – The moderate-to-severe reduction in platelet count usually occurs gradually after 5–10 days. Delayed-onset HIT can present with a fall in platelet count days or weeks after heparin exposure. – Platelet count is usually around 50 × 109/L (alternatively, there is a 50% reduction from baseline). However, the platelet count can also be normal if a 50% reduction occurred after an elevated baseline count. – Unless heparin is stopped, the platelet count will not return to baseline. – Thrombotic complications are common, whereas bleeding is rare. Thromboses can occur in veins, arteries or both, depending on the clinical setting. – In postoperative patients, deep vein thrombosis (DVT) and pulmonary embolism are more common. Venous thrombosis can be severe and can even cause venous gangrene. – In patients with a history of peripheral vascular disease and advanced artherosclerosis,

arterial thrombosis is more common and can lead to limb gangrene and leg amputation. • Laboratory testing. Can be helpful in the confirmation of HIT, but is less important if the clinical picture is clear. Additionally, the assays with the highest sensitivity and specificity may not be readily available and have a slow turnaround time. If laboratory tests are needed to make a diagnosis decision, treatment should not be withheld. They are divided into either functional tests or immunoassays: – Functional tests assess platelet activation and altered platelet function caused by HIT antibodies. C-serotonin release assay (SRA) is considered the gold standard with a 90–98% sensitivity. It has a 95% specificity for early-onset HIT and a 80–97% specificity for lateonset HIT. Heparin-induced platelet aggregation (HIPA) has a 90–98% sensitivity. It has a 95% specificity for early HIT and 80–97% specificity for late-onset HIT. – Immunoassays. Enzyme-linked immunosorbent essay (ELISA) is the most common. The solid-phase anti-PF4/heparin ELISA complex detects HIT antibody binding. ELISA can show false positives since it detects all antibodies (even those not causing HIT). ELISA has a >91–97% sensitivity. It has a >95% specificity with early platelet fall and a 50–93% specificity with a late platelet fall. • Doppler of extremities should be considered to rule out thrombosis.

DIFFERENTIAL DIAGNOSIS

Thrombocytopenia caused by • Drugs such as glycoprotein IIb/IIIa inhibitors and antibiotics • Sepsis • Disseminated intravascular coagulopathy • Pulmonary thromboembolism • Bone marrow disease • Intra-aortic balloon pumps • Hemofiltration therapies

TREATMENT • Type I: Since type 1 is usually transient and clinically insignificant most patients remain asymptomatic and no specific treatment is required. If it is difficult to differentiate between type I and type II, the patient should be treated as having type II. • Type II: – Discontinuation of all sources of heparin, including LMWH and heparin-coated catheters. – Avoid prophylactic platelet transfusions. – Give alternative anticoagulant to avoid clot formation while the platelet count recovers and antibody formation decreases. Alternative anticoagulation includes either direct thrombin inhibitors (lepirudin, bivalirudin, argatroban) that reduce activity of thrombin or heparinoids (danaparoid, fondaparinux) that reduce thrombin formation. These drugs act immediately and should be continued for at least 5 days or until thrombosis is under control.

– Warfarin is not an option for immediate alternative anticoagulation. Since warfarin initially decreases protein C levels faster than the coagulation factors, it can worsen thrombosis and cause leg gangrene and cutaneous necrosis. Treatment with danaparoid, lepirudin, bivalirudin, or argatroban should overlap warfarin therapy for a few days. – Thrombolytic therapy may be needed in patients with severe DVT and limb gangrene or pulmonary embolism. – In patients who cannot be anticoagulated, an inferior vena cava filter can be placed. – Embolectomy might be necessary in some cases.

FOLLOW-UP • Serial platelet counts should be performed. • HIT antibodies usually disappear in a 100 days after the onset of HIT. • To prevent the recurrence of thrombosis, long-term treatment (e.g., for 6 months) is usually required. • Re-exposure. Heparin is unlikely to result in a recurrence of HIT; however, recommendations lean toward heparin avoidance in the future if possible. – If no heparin alternative is available, negative HIT antibodies need to be confirmed and heparin should only be used for a short period of time. – Patients with positive HIT antibodies needing noncardiac surgery with anticoagulation (e.g., vascular surgery) can be given argatroban as an alternative to heparin. – Elective cardiac surgery with cardiopulmonary bypass (CPB) should be postponed in patients with positive HIT antibodies until the platelet count is restored and HIT antibodies are eliminated from the circulation. Heparin should only be used during the surgery, and an alternative anticoagulant should be used pre- and postoperatively. – If cardiac surgery cannot be postponed and HIT antibodies are still present, consider the following alternatives: Bivalirudin for anticoagulation on CPB Lepirudin during off-pump cardiac surgery Heparin plus the antiplatelet agent tirofiban or danaparoid.

REFERENCES

1. Chong BH. Heparin-induced thrombocytopenia. J Thromb Haemost. 2003 Jul;1(7):1471– 1478. 2. Shantsila E, et al. Heparin-induced thrombocytopenia: A contemporary clinical approach to diagnosis and management chest. 2009;135(6):1651–1664.

ADDITIONAL READING

• www.heparininducedthrombocytopenia.com

See Also (Topic, Algorithm, Electronic Media Element) • Cardiopulmonary bypass • Thrombocytopenia

CODES ICD9

289.84 ICD10 D75.82 Heparin induced thrombocytopenia (HIT)

CLINICAL PEARLS

• Recognize thrombocytopenia in the setting of heparin administration. Thrombocytopenia is defined as a >50% reduction from baseline platelet count or absolute values <100 × 109/L after 5–10 days of heparin administration • HIT carries a high risk for thrombosis and thromboembolic events. • If Type 2 HIT is suspected, heparin, LMWH, and all heparin sources need to be discontinued and alternative anticoagulation should be started.

HEPATIC ENCEPHALOPATHY Allyson J.A. Morman, MD Keith E. Littlewood, MD

BASICS DESCRIPTION

• Hepatic encephalopathy (HE) is a serious, progressive, and reversible metabolic encephalopathy characterized by neuropsychiatric abnormalities and neuromuscular dysfunction that range from mild cognitive and motor impairment to coma and death. • HE results from the abnormal accumulation of toxic substances that are normally cleared (detoxified) by the liver. EPIDEMIOLOGY Incidence

New or worsening HE occurs in 30–35% of patients following a transjugular intrahepatic portosystemic shunt (TIPS) procedure (1).

Prevalence

• Minimal HE occurs in 60–80% of patients with cirrhosis. • Overt hepatic encephalopathy (OHE) can be seen in 30–45% of patients with advanced liver disease. Morbidity

Severely impairs driving skills and/or work performance. Mortality

After the 1st occurrence of OHE, mortality at 1 year was 42% and 23% at 3 years (2).

ETIOLOGY/RISK FACTORS

• GI bleeding (excess protein load) • Sepsis • Dehydration (excessive diuretics, vomiting, diarrhea) • Hyponatremia, hypokalemia • Postsurgical states • Medication noncompliance • Sedative use (opiates, benzodiazepines, antidepressants) • TIPS placement • Constipation • Excessive dietary protein

PATHOPHYSIOLOGY

• Elevated levels of ammonia in the presence of an inflammatory response cause astrocyte swelling and fluid accumulation in the brain (cerebral edema). – Ammonia is normally converted to urea by the liver; however, with liver failure, ammonia concentrations rise. – An alternative pathway in muscle (via glutamine synthetase enzyme) serves to metabolize ammonia to glutamine. Saturation of this secondary pathway leads to accumulation of ammonia in plasma that easily passes through the blood-brain-barrier and comes into contact with astrocytes. – Astrocytes convert excess ammonia to glutamine intracellularly. This process will lead to cellular swelling, cerebral edema, and ultimately increased intracranial pressure (ICP). • Historically, the role of ammonia accumulation has dominated explanations of pathogenesis, but it is now recognized that the pathogenesis is multifactorial. Oxidative stress, endogenous benzodiazepine-like ligands, astrocyte swelling, GABA-like molecules, abnormal histamine and serotonin neurotransmission, endogenous opioids, neurosteroids, inflammatory cytokines, and manganese toxicity are other potential mediators of pathogenicity.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess the severity of HE and treat underlying as well as precipitating causes prior to surgery. Emergent cases may require proceeding with concurrent perioperative management. • Pharmacokinetic alterations can include: Decreased hepatic metabolism; decreased albumin leading to less protein binding (more free drug available); and increased volume of distribution due to ascites and increased total body water compartments.

PREOPERATIVE ASSESSMENT SYMPTOMS

Difficulty concentrating, increasing pruritus History

• Course of HE • Assess for the presence of comorbidities: History of esophageal varices, easy bruising, ascites, orthodeoxia/platypnea, renal dysfunction • Recent paracentesis

Signs/Physical Exam

• Altered mental status, ascites, peripheral edema, jaundice, asterixis. • In severe cases (e.g., type A), may see muscular rigidity or clonus, extensor plantar responses, slurred speech, tremor, or decerebrate posturing.

TREATMENT HISTORY Liver transplantation MEDICATIONS

• Lactulose; first-line therapy with a direct effect on the GI system. It is a nonabsorbable disaccharide that is fermented in the colon and reduces the intestinal production and absorption of ammonia. • Rifaximin; direct effect on the GI system. A nonabsorbable antibiotic that is very expensive and reserved for patients who are either intolerant or refractory to lactulose. Its cost, however, may be justified by the reduced need for hospitalization. • Flumazenil; direct neurological therapy. A GABA antagonist that can produce short-term reversal of HE symptoms. Has fallen out of favor secondary to its potential to decrease the seizure threshold and its transient efficacy. • Metronidazole and neomycin; antibiotics that reduce intestinal ammonia production. However, it lacks data that support its efficacy. – Long-term neomycin administration is associated with nephrotoxicity and ototoxicity. – Long-term metronidazole administration is associated with peripheral neuropathy. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Arterial ammonia levels. In acute liver failure, ammonia levels >200 μg/L were found to be almost invariably associated with cerebral uncal herniation in patients with grade 3 and 4 HE (3). Otherwise, ammonia levels (especially ones that are drawn venously) are not reliable indicators of severity of HE. • Sodium levels. Hyponatremia is present in ~25% of patients with acute liver failure; it becomes more prominent with severe encephalopathy. • CBC, PT/PTT/INR

CONCOMITANT ORGAN DYSFUNCTION End stage liver disease

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Overt hepatic encephalopathy (OHE) should be optimized medically and the underlying etiology addressed prior to an elective and possibly an urgent procedure. This may not always be possible, as with GI bleeding (etiology) or other emergent cases. • Coagulopathy • Poor nutrition status • Hypovolemia

CLASSIFICATIONS

• Overt hepatic encephalopathy (OHE). Combination of neurological and neuropsychiatric abnormalities that can be detected by bedside clinical tests. • Minimal hepatic encephalopathy (MHE). Normal mental and neurological function but abnormal results on formal neuropsychometric testing. • World Congresses of Gastroenterology Classification System – Type A: Associated with acute liver failure. Increased incidence of elevated ICP that can lead to brain stem herniation and death. Thirty percent mortality rate if the ICP is elevated (4). – Type B: Associated with portosystemic bypass without intrinsic liver disease

– Type C: Associated with cirrhosis • West Haven Criteria. Grades the severity of HE and is based on intellect/behavior as well as level of consciousness and neurological findings. – Grade 1 – Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction. – Grade 2 – Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behavior. – Grade 3 – Somnolence to semistupor, but responsive to verbal stimuli; confusion; gross disorientation. – Grade 4 – Coma (unresponsive to verbal or noxious stimuli). • Childs–Pugh class score measures lab values (total bilirubin, serum albumin, PT/INR) and clinical symptoms (ascites, hepatic encephalopathy) to assess perioperative mortality risk. Class A is 10%, Class B is 30%, Class C is 82%. • Model for end-stage liver disease (MELD) score. Originally developed to predict short-term mortality in patients undergoing a TIPS procedure, but currently being used as a predictor for 30-day postoperative mortality and organ allocation in the US (5). It provides an objective measure and is based on laboratory values (INR, bilirubin, creatinine). A score of 5 has a 5% risk; a score of 10 has a 7% risk; a score of 15 has a 11% risk; a score of 20 has a 17% risk; and a score of 25 has a 26% risk.

TREATMENT PREOPERATIVE PREPARATION Premedications

• If benzodiazepines are needed, they should be short-acting and given in reduced doses (drug clearance is reduced, half-life increased). • Fentanyl can be used safely despite being almost completely metabolized by the liver.

Special Concerns for Informed Consent

• Patient may not be able to provide consent. • Increased risk of morbidity and mortality that need to be weighed against the urgency of the procedure. • Potential for postoperative intubation.

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia is commonly chosen to provide airway protection in grade III or IV HE (bleeding varices, ascites, obtundation), or manage ICPs, esophageal varices, severe ascites, or obtundation. • Any patient presenting with moderate encephalopathy has impaired liver failure and drugs/dosages should be modified appropriately. Monitors

• Consider neurosurgical consultation for the placement of an ICP monitoring device. • Consider an arterial line in high-risk patients in order to closely monitor acid/base status.

Induction/Airway Management

• Consider a rapid sequence induction or awake intubation in patients with concurrent GI bleeding/history of esophageal varices. • Pharmacokinetic profile of propofol is not significantly altered in the presence of liver disease and is thus a safe induction agent; however, may cause hypotension. • Nondepolarizing muscle relaxants selection. Most have prolonged half-lives because of impaired biliary excretion. Atracurium and cisatracurium do not rely on hepatic or renal excretion (Hoffmann elimination). • Anticipate hypotension as endogenous stores of catecholamines are often depleted and wider swings in BP can be expected.

Maintenance

• Volatile anesthetics. Isoflurane and desflurane are preferred (low hepatic metabolism, less effects on hepatic blood flow); however, sevoflurane is probably also appropriate. Avoid halothane and enflurane: Decreases total hepatic blood flow and their higher hepatic metabolism leads to formation of adducts. Adducts are formed with liver proteins that can be recognized as neoantigens. They are associated with the production of humoral and cellular immune responses that are involved in hepatotoxicity. • Opioid selection. Fentanyl has advantages already noted. When utilized, other opioids should be given at reduced doses secondary to their toxic metabolites (meperidine) and/or prolonged duration of action (morphine, hydromorphone). • Maintain ICP <20–25 mm Hg with a CPP >50–60 mm Hg. Prolonged ICP >40 mm Hg and CPP <50 mm Hg have been shown to be associated with poor outcome (3). Mannitol, hyperventilation, head-up position, and hypertonic saline may be considered. • Consider empiric antibiotics if the precipitating cause of the HE episode remains undefined. • Meperidine has prolonged duration of action as does its major metabolite, normeperidine (more susceptible to seizures), and should be avoided. Extubation/Emergence

If the ICP is increased, or there is a risk for aspiration (AMS, grade III or IV HE), consider leaving the patient intubated to manage PaCO2 most effectively.

POSTOPERATIVE CARE BED ACUITY

Admit to ICU if surgery is prolonged, cardiac and/or pulmonary surgery were performed, intraoperative hypotension, excessive blood loss, or Grade III/IV HE. MEDICATIONS/LAB STUDIES/CONSULTS

• Continue preoperative lactulose and antibiotics. • Carefully titrate sedatives and pain medications to prevent exacerbation. • Consider hepatology or GI consult.

COMPLICATIONS

• Worsening jaundice, encephalopathy, and ascites • Hepatorenal syndrome • Development of sepsis and secondary disseminated intravascular coagulation.

REFERENCES

1. Somberg KA, Riegler JL, LaBerge JM, et al. Hepatic encephalopathy after transjugular intrahepatic portosystemic shunts: Incidence and risk factors. Am J Gastroenterolgy. 1995;90:549–555. 2. ustamante J, et al. Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999;30(5):890–895.

3. roglu Y, Byrne WJ. Hepatic encephalopathy. Emerg Med Clin N Am. 2009;27:401–414. 4. Shawcross D, Jalan R. The pathophysiological basis of hepatic encephalopathy: Central role for ammonia and inflammation. Cell Mol Life Sci. 2005;64:2295–2304. 5. Northup PG, et al. Model for end-stage liver disease (MELD) predicts nontransplant surgical mortality in patients with cirrhosis. Ann Surg. 2005;242(2):244–251. 6. Bajaj JS. The modern management of hepatic encephalopathy. Aliment Pharmacol Ther. 2010;31:537–547. 7. Furst SM, Chen M, Gandolfi AJ. Use of halothane as a model for investigating chemicalinduced autoimmune hepatotoxicity. Drug Inf J. 1996;30(1):301–307.

ADDITIONAL READING •

The American College of Gastroenterology http://www.acg.gi.org/physicians/clinicalupdates.asp

Clinical

Practice

Guidelines:

See Also (Topic, Algorithm, Electronic Media Element) • End-stage liver disease • Hoffman elimination

CODES ICD9 572.2 ICD10 K72.90 Hepatic failure, unspecified without coma

CLINICAL PEARLS

• Infection/inflammation and oxidative stress act synergistically with ammonia to create the pathogenesis of the clinical syndrome. Most commonly, the precipitating incident is either

medication noncompliance or infection. Empiric antibiotics should be started. • Serum ammonia levels are elevated in 90% of patients, but encephalopathy can be present with normal serum ammonia levels as well. • Catecholamine and other neurohormonal responses are impaired in patients with liver disease. Thus, intraoperative hypovolemia or hemorrhage may not be able to trigger adequate compensatory mechanisms. Subsequent decreases in oxygen delivery to the liver can further worsen hepatic dysfunction.

HEPATITIS C Neesa Patel, MD

BASICS DESCRIPTION

• Hepatitis C is a virus that can cause acute and chronic inflammation of the liver. Clinical presentation can range from inactive, dormant carrier states to severe fibrosis, cirrhosis, end-stage liver disease, or hepatocellular carcinoma. • Patients with hepatitis C can present perioperatively for procedures that are related (e.g., liver transplantation, transjugular intrahepatic portosystemic shunt (TIPS), and liver resection) and unrelated to liver disease. • Healthcare workers are at an increased risk for exposure due to needlestick injuries. The average incidence of seroconversion to hepatitis C virus (HCV) after unintentional needle sticks or sharps exposures from an HCV-positive source is 1.8% (range of 0–7%) (1). • Unfortunately, at this time there is no proven effective postexposure prophylaxis for persons exposed to HCV blood or contaminated body fluids. EPIDEMIOLOGY Prevalence

• In the US: 28,000 new infections/year • Chronic hepatitis develops in about 85% of those infected.

Prevalence

In the US, there are an estimated 3.2 million persons (1.3% of the population) (2).

Morbidity

It is the leading cause of liver transplantation, accounting for 30% of all liver transplants. Mortality

Chronic HCV accounts for 8–10,000 deaths/year ETIOLOGY/RISK FACTORS

The US Centers for Disease Control and Prevention (CDC) recommend assessment of HCV risk factors; those with risk factors should be screened for HCV antibodies (anti-HCV). The American Association for the Study of Liver Diseases rates the level of evidence for screening in all of the following risk groups as class 1B (3): • High risk: IV drug abusers, hemophilia patients treated with clotting factor concentrates produced before 1987, HIV-positive patients • Intermediate risk: Recipients of blood transfusions or solid organ transplants before 1992, patients with unexplained elevated aminotransferase levels, patients born from infected mothers.

• Low risk: People who have had sexual relations with multiple or infected partners; healthcare workers exposed to HCV (e.g., needlestick) (4).

PHYSIOLOGY/PATHOPHYSIOLOGY

• HCV replicates within hepatocytes but can be found in multiple sites throughout the body. It is not directly hepatotoxic. • Liver parenchyma damage is mediated by inflammatory cytokines that lead to varying degrees of hepatic fibrosis. Only some patients develop progressive fibrosis and eventually cirrhosis. Predictors of progression include – Advanced age at the time of infection – Male gender – Excessive alcohol use – Co-infection with hepatitis B virus (HBV) – Hemophiliacs with multiple transfusions – Injection drug users and HIV – Persistently elevated aminotransferase activity – Concomitant liver disease (5–7) • Because the immune system’s antibody response cannot clear the infection, there is slow progress in the development of a vaccine.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Hepatitis C infection alone without end-organ damage usually does not require specific perioperative considerations. However, even asymptomatic patients should be screened before elective surgery; the INR is the most sensitive indicator of disease severity. • Patients who have developed liver disease or cirrhosis should be carefully evaluated and optimized prior to surgery. Perioperative goals should include maintaining hepatic perfusion and avoiding factors that might precipitate liver failure or hepatic encephalopathy. • Elective surgery should be delayed in patients with acute hepatitis of any etiology until resolution (8).

PREOPERATIVE ASSESSMENT SYMPTOMS

• Chronic hepatitis C infection is usually asymptomatic. • In the acute phase, look for signs of acute hepatitis: Malaise, nausea, and right upper quadrant pain, followed by dark urine and jaundice. • Patients with uncompensated end-stage liver dysfunction can present with signs of encephalopathy.

History

• Assess for risk factors and consider screening as appropriate • Clinically important hepatic dysfunction is more likely to occur in patients with preexisting liver disease.

Signs/Physical Exam

Acute hepatitis: Myalgia, right upper quadrant pain, anorexia. However, it is also frequently asymptomatic (many patients may hence be unaware of infection or carrier status). TREATMENT HISTORY

• Liver transplantation • TIPS • Large volume paracentesis • Endoscopic variceal ligation

MEDICATIONS

• Interferon-alpha and oral ribavirin during the first 6 months of infection. • Diuretics (spironolactone) for ascites • Antibiotics (cephalosporins) for spontaneous bacterial peritonitis • Lactulose and poorly absorbable antibiotics (rifaximin, neomycin, metronidazole) for hepatic encephalopathy. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Enzyme immunoassays (EIAs) for diagnosing HCV infection are recommended as the initial serologic test for screening populations at risk. • A positive anti-HCV EIA requires HCV RNA measurement to discriminate between current infection on the one hand, and either resolved HCV infection or a false-positive result on the other (4) • CBC • Coagulation studies: INR is the most sensitive indicator of severity of disease • Complete metabolic panel

CONCOMITANT ORGAN DYSFUNCTION

Cirrhosis and end-stage liver disease manifest as impaired hepatic synthesis and metabolism as well as increased hepatic vascular pressures:

• CNS: Encephalopathy, asterixis, peripheral neuropathy • Cardiovascular: Decreased systemic vascular resistance, high output cardiac failure • Pulmonary: Pulmonary shunting may cause hypoxemia and pulmonary hypertension; pleural effusions • Hepatic: Cirrhosis, portal hypertension, varices, ascites, splenomegaly • Renal: Insufficiency or failure; hepatorenal syndrome describes renal disease in the absence of primary disease and may be related to hypoperfusion. • Coagulation: Decreased production of hepatic synthesized factors, thrombocytopenia • Infectious: Spontaneous bacterial peritonitis • Cutaneous: Jaundice, palmar erythema, spider nevi, male gynecomastia

CIRCUMSTANCES TO DELAY/CONDITIONS

• Elective surgery should be delayed in patients with acute hepatitis of any etiology until

resolution of hepatocellular dysfunction (1). • When surgery cannot be avoided, meticulous care should be taken perioperatively to maintain hepatic perfusion and avoid factors that might precipitate liver failure, hepatic encephalopathy, or both.

CLASSIFICATIONS

• Acute infection – Symptoms consistent with acute viral hepatitis along with jaundice/dark urine or serum alanine aminotransferase levels >400 IU/L – Positive hepatitis C antibody (anti-HCV), recombinant immunoblot assay (HCV RIBA), or nucleic acid test (NAT). – Combined with a negative IgM antibody to hepatitis A virus and hepatitis B core antigen • Chronic infection – Symptoms may range from none to severe – Positive anti-HCV by EIA combined with either a more specific assay or HCV RIBA, or NAT.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis may be administered safely in asymptomatic patients with normal liver function tests. • Correct coagulopathies with vitamin K and fresh frozen plasma. • Correct electrolyte abnormalities • Intravascular volume repletion

Special Concerns for Informed Consent

Depending on the severity of liver dysfunction, anesthetic morbidity, and mortality rise INTRAOPERATIVE CARE Choice of Anesthesia

• Asymptomatic without ESLD can be performed with general, regional, or deep sedation depending on the surgical procedure and patient preference. • In coagulopathic patients, neuroaxial blocks should be avoided. Regional techniques may be acceptable but risks of bleeding should be weighed against the benefits of avoiding general anesthesia. Monitors

• Standard ASA monitoring • Invasive monitoring such as an arterial or central line may be appropriate depending on the extent of the procedure and liver disease severity. Induction/Airway Management

• A standard induction may be appropriate in patients without (or only minimal) liver dysfunction • If significant liver dysfunction, use caution with benzodiazepines, morphine, demerol, neuromuscular agents.

Maintenance

Volatile agents. Halothane and enflurane appear to reduce hepatic artery blood flow via systemic vasodilation and a mild negative inotropic effect. Halothane is also associated with hepatotoxicity. Extubation/Emergence Standard precautions

FOLLOW-UP BED ACUITY

• Depends on extent of liver disease, surgical procedure, and intraoperative course. • Monitor for signs of acute liver failure, including worsening jaundice, encephalopathy, and ascites.

MEDICATIONS/LAB STUDIES/CONSULTS

• Patients with preoperative acute hepatitis or cirrhosis from hepatitis C are at increased risk of postoperative jaundice. • Patients with more advanced liver disease (CTP class B or C cirrhosis) are at increased risk of encephalopathy, cerebral edema, coagulopathy, hemorrhage, and portal hypertension.

COMPLICATIONS

• Infectious exposure to the hepatitis C patient – Cuts or needle-stick injuries may occur in up to 15% of all surgeries. – The risk of HCV transmission depends on the volume of blood transmitted, but <0.5% of such injuries are considered high risk (e.g., hollow-bore needle) (9). – There is no vaccine or immunoglobulin to protect against transmission. Additionally, prophylactic post-exposure treatment with interferon and/or ribavirin is not recommended. – At this time, the following recommendations are: Baseline testing of the injured for anti-HCV and ALT activity Follow-up testing 4–6 months for anti-HCV and ALT activity or HCV RNA at 4–6 weeks Careful monitoring for laboratory abnormalities and signs/symptoms of acute infection Avoidance of blood, plasma, organ, tissue, or semen donation

REFERENCES

1. holson CF, Provenza JM, Bacon BR. Hepatologic considerations in patients with parenchymal liver disease undergoing surgery. Am J Gastroenterol. 1990;85:487–496. 2. Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in

the United States, 1999 through 2002. Ann Intern Med. 2006;144:705–714. 3. Ghany MG, Strader DB, Thomas DL, et al., American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: An update. Hepatology. 2009;49:1335–1374. 4. Albeldawi M, Ruiz- Rodriguez E, Carey WD. Hepatitis C virus: Prevention, screening, and interpretation of assays. Cleve Clin J Med. 2010;77(9):616–626. 5. Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection: Host, viral, and environmental factors. JAMA. 2000;284:450–456.

6. Seeff LB. Natural history of chronic hepatitis C. Hepatology. 2002;36:S35–S46. Shakil AO, Conry-Cantilena C, Alter HJ, et al. Volunteer blood donors with antibody to hepatitis C virus: Clinical, biochemical, virologic, and histologic features. Ann Intern Med. 1995;123:330–337.

7. Gholson CF, Provenza JM, Bacon BR. Hepatologic considerations in patients with parenchymal liver disease undergoing surgery. Am J Gastroenterol. 1990;85:487–496. 8. U.S. Public Health Service. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm Rep. 2001;50(RR-11):1. See Also (Topic, Algorithm, Electronic Media Element) • Liver resection • Liver transplant • Transjugular intrahepatic portosystemic shunt (TIPS) • Cirrhosis • End-stage liver disease • Postoperative jaundice • Hepatic encephalopathy • Infectious disease exposure in the healthcare worker

CODES ICD9 • 070.51 Acute hepatitis C without mention of hepatic coma • 070.54 Chronic hepatitis C without mention of hepatic coma • 070.70 Unspecified viral hepatitis C without hepatic coma ICD10 • B17.10 Acute hepatitis C without hepatic coma • B18.2 Chronic viral hepatitis C • B19.20 Unspecified viral hepatitis C without hepatic coma

CLINICAL PEARLS

• Patients with asymptomatic Hepatitis C infection alone usually tolerate anesthesia without

sequela. • Elective surgery should be delayed in patients with acute hepatitis. • Care should be taken when clinical signs of cirrhosis are apparent.

HERNIORRHAPHY Emily L. Drennan, MD

BASICS DESCRIPTION General

• A hernia is defined as a protrusion of any viscous structure from its proper cavity. • Hernias can occur at any point in the abdominal wall, but some of the more common are – Inguinal and femoral (groin hernias) occur from defects in the transverse abdominis layer. Direct hernias protrude through the posterior wall of the inguinal canal, whereas indirect hernias protrude through the internal inguinal ring. – Umbilical hernias may be congenital or acquired. Congenital hernias arise from a weakness in the area where the fetal vessels exited the muscular layer of the abdominal wall. Umbilical hernias may also develop later in life, as continued tension in the same area leads to progressive weakening of the muscular layer and eventual protrusion of abdominal contents. – Incisional hernias occur from prior surgical incisions. They are more common following midline incisions, wound infection, or trauma. • Hernia descriptions – Reducible hernias refer to the ability to replace the contents of the hernia sac within their proper cavity with pressure. – Nonreducible hernias cannot be replaced with pressure. – Incarcerated hernias occur when a portion of bowel becomes trapped in the defect and the blood supply to that portion is compromised. • The size of the hernia is not as important as the size of the defect in the abdominal wall, as a small defect is more prone to entrap and strangulate bowel. • Elective versus emergent repair – Elective repair is performed to avoid the complication of incarceration and bowel obstruction. – Emergent repair is performed when symptoms and physical exam indicate the hernia is incarcerated and to avoid bowel necrosis and intra-abdominal sepsis. • Mesh may be used as an adjunct to the primary repair in order to reinforce the repair or “plug” the defect. The use of mesh is possible with umbilical or groin hernias, depending on the approach taken for the repair. • Laparoscopic versus open depends on surgeon preference and characteristics of the hernia such as location, size, and adherence of intra abdominal contents to the site of defect. – Groin hernia: Laparoscopic or open; the laparoscopic approach may be preperitoneal or intraperitoneal. – Ventral hernia: Laparoscopic or open – Umbilical hernia: Laparoscopic or open

Position

• Inguinal: Supine • Ventral: Supine

Incision

• Ventral, umbilical, incisional: Incision at the site of defect • Inguinal – Open: Three- to four-inch groin incision – Laparoscopic: Three or four one-inch incisions for trochar insertion

Approximate Time

• Length of case depends on the extent of the hernia. • Open inguinal hernia repairs last approximately 1 hour.

EBL Expected

• Minimal • Large abdominal hernia repairs with extensive lysis of bowel adhesions may result in significant blood loss that is difficult to quantitate because it is not captured with the suction.

Hospital Stay

• Straightforward hernia repairs may be performed on an outpatient basis. • More extensive repairs, incarcerated hernias, or defects causing bowel obstruction require more extensive hospitalizations for pain control and return of bowel function.

Special Equipment for Surgery

• Laparoscopic repairs: Laparoscopy monitors, cameras, trochars, etc. • Mesh

EPIDEMIOLOGY Incidence

• In the US: >1 million hernia repairs are performed annually; it is the most commonly performed general surgery procedure. • Inguinal hernias are the most common type. • Men are affected more than women, by as much as a 19:1 ratio. • Inguinal hernia incidence in children is as high as 4.4%.

Prevalence

Inguinal hernia estimated at 4.6% Morbidity

• Related to complications of repair – Adhesions – Infection – Chronic pain

– Hernia recurrence • Related to complications of missed diagnosis – Incarcerated bowel – Bowel obstruction – Peritonitis

Mortality

• Insignificant for elective hernia repairs • Emergent hernia repairs carry up to a seven-fold increased mortality risk; this is related to advanced age, ischemic bowel/need for bowel resections.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Neuraxial techniques may be utilized as a sole technique (inguinal, femoral) or an adjunct to a general anesthetic (incisional, umbilical). • Minimize postoperative morbidity that can delay discharge home (nausea, pain).

PREOPERATIVE ASSESSMENT SYMPTOMS

• It is very common to have an asymptomatic hernia. • Fullness at site • Ache or pain radiating into site • Incarcerated hernia can present with pain at the site, nausea, and vomiting.

History

• Swelling or fullness at site that is associated with increases in intra-abdominal pressure • History or prior abdominal surgery • Family history of hernia • Medical condition, such as BPH or chronic cough, that lead to increases in intra-abdominal pressure. • New onset nausea, vomiting, and abdominal pain may indicate a hernia involving bowel obstruction.

Signs/Physical Exam

• Mass at site, visible with standing or increased intra-abdominal pressure • If mass or fullness is present, assessing the mobility is important.

MEDICATIONS None

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Preoperative labs as indicated for patient’s comorbidities • KUB or CT scan to evaluate for obstruction and extent of hernia. • If incarceration is suspected, WBC and/or BMP are indicated to evaluate for sepsis and

electrolyte abnormalities.

CONCOMITANT ORGAN DYSFUNCTION

Incarcerated hernias may have other organs involved; the most common is small bowel or colon, presenting as obstruction or strangulation.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Standard, unless evidence of obstruction • Incarcerated hernia carries a high-risk for aspiration; consider an H2 blocker. Avoid metoclopramide in the setting of obstruction

Special Concerns for Informed Consent

If the planned procedure is laparoscopic, consent for open as well. Antibiotics/Common Organisms

• First-generation cephalosporin • Skin flora, including staphylococcus and streptococcus, are most common

INTRAOPERATIVE CARE Choice of Anesthesia

• Groin hernias – Local with a genitofemoral, iliohypogastric, or ilioinguinal nerve block – Paravertebral block – Neuraxial block – General anesthesia • Ventral and umbilical hernias – General – Neuraxial • Laparoscopic procedures must be performed with general endotracheal anesthesia.

Monitors

Standard ASA

Induction/Airway Management

• For open procedures, an LMA may be appropriate if muscle relaxation is not necessary (groin hernias). • Consider rapid sequence induction with cuffed endotracheal tube intubation in patients at risk for aspiration or emergent repairs. Maintenance

• Balanced inhaled or IV agent with or without muscle relaxant as needed for surgical

exposure and closure. • For groin hernia under local anesthesia, consider small boluses of benzodiazepines, opioids, or propofol (consider infusion).

Extubation/Emergence

• Avoidance of coughing and bucking is desired to avoid increases in abdominal pressure with resultant tearing of sutures or displacement of mesh. A deep or comfortable extubation may be considered, if appropriate. • If bowel obstruction is present preoperatively, then the patient should be extubated when fully awake, fully reversed, and capable of protecting their airway.

Pediatric Considerations

• Groin hernias are the most common in children. • Pediatric patients have lower recurrence rates once the hernia defect is fixed. • Caudal blocks provide excellent postoperative analgesia. • Infants with significant pulmonary comorbidities are good candidates for hernia repair under spinal anesthetic. • There is no clear benefit to laparoscopic hernia repair in children, and it may increase operative time, cost, and postoperative discomfort.

POSTOPERATIVE CARE BED ACUITY

• Elective hernia repair appears to carry minimal increased risk of morbidity or mortality (particularly when groin hernia repair is performed under local anesthesia). • Emergent hernia repairs may be complicated by postoperative sepsis related to bowel involvement.

ANALGESIA

• Local infiltration of the wound appears to provide the best postoperative pain relief • Regional anesthesia (caudal, continuous epidural catheter, long acting epidural morphine, tranversus abdominus plane (TAP) block) • Opioid of choice • NSAIDs such as IV ketorolac or PO ibuprofen; PO acetaminophen

COMPLICATIONS

• Recurrence of hernia – 10% with open repair – 1% if mesh utilized • Damage to surrounding structures, that is, bowel, bladder, spermatic cord, nerves, blood vessels • Bleeding • Infection • Chronic postoperative pain • Postoperative urinary retention

PROGNOSIS

• Excellent overall prognosis, excluding recurrence risk • Emergent repair carries a significant increase in 30-day postoperative mortality.

REFERENCES

1. Kendell J,Wildsmith JAW, GrayIG. Costing anaesthetic practice. An economic comparison of regional and generalanaesthesia for varicose vein and inguinal hernia surgery. Anaesthesia.2000;55:1106–1126.

2. Song D, Greilich NB, White PF, et al. Recovery profiles and costs of anesthesia for outpatient unilateral inguinal herniorrhaphy. Anesth Analg. 2000;91:876–881.

3. Koivusalo AI, Korpela R, Wirtavuori K, et al. A single-blinded, randomized comparison of laparoscopic versus open hernia repair in children. Pediatrics. 2009;123(1):332–337. See Also (Topic, Algorithm, Electronic Media Element) • Laparoscopy • Deep extubation

CODES ICD9 • 553.8 Hernia of other specified sites without mention of obstruction or gangrene • 553.9 Hernia of unspecified site without mention of obstruction or gangrene ICD10 • K46.0 Unsp abdominal hernia with obstruction, without gangrene • K46.1 Unspecified abdominal hernia with gangrene • K46.9 Unspecified abdominal hernia without obstruction or gangrene

CLINICAL PEARLS

• For non-emergent groin hernias, open hernia repair under local anesthesia with sedation has the best risk and cost profile as well as patient satisfaction. • Emergent surgery for hernia repair carries a significant mortality risk; thus elective repair, when feasible, is preferable, especially if the defect is small.

HIATAL HERNIA

Zhuang-Ting Fang, MD, MSPH

BASICS DESCRIPTION

• Hiatal hernia is a protrusion of a portion of the stomach through the diaphragmatic esophageal hiatus into the thoracic cavity. • The impaired ability of the lower esophageal sphincter (LES) to protect against reflux of gastric contents, places the patient at an increased risk for aspiration. Thus, there is a potential for patients in the perioperative period to have an – Aspiration pneumonitis – Aspiration pneumonia (a more delayed manifestation) • The majority of patients with hiatal hernia are treated medically for the symptoms of gastroesophageal reflux disease (GERD). Patients whose symptoms are not well controlled prior to surgery should be treated as having an increased aspiration risk. EPIDEMIOLOGY Incidence

• Increases with age: ~10% in patients <40 years of age compared to ~70% in patients >70 years of age. • Increased incidence with morbid obesity

Prevalence

Hiatal hernia is common; 30% of patients undergoing upper GI examination by radiography were found to have a sliding type hiatal hernia. Morbidity

Surgical repair exposes patients to an approximately 24% postoperative morbidity. Mortality

Surgical repair carries an increased risk of mortality (as high as 2.4%) in elderly patients secondary to comorbidities and surgical complications. ETIOLOGY/RISK FACTORS

• Hiatal hernia may be congenital or acquired • Predisposing factors for acquired hiatal hernia: – Weakening of muscle and loss of elasticity when people age – Women, which may result from the increased intra-abdominal pressure during pregnancy – Obesity from increased abdominal pressure – Chronic constipation due to low fiber diet – Abdominal ascites

PATHOPHYSIOLOGY

• The upper part of the lower esophageal sphincter (LES) normally lies within the diaphragmatic hiatus, while the lower portion is normally intra-abdominal. The LES is maintained within the abdominal cavity by the phrenoesophageal ligament. The angle of His between the cardia of the stomach and the distal esophagus prevents reflux of gastric contents into the esophagus. • There are two types of hiatal hernia – Sliding hiatal hernia: A portion of the stomach and lower esophagus slide up into the thoracic cavity. This is the most common type. – Paraesophageal hernia: A portion of the stomach herniates through the hiatus, while the esophagogastric junction remains in its normal anatomical location. It is less common, but can lead to ischemia of the herniated part of the stomach if it becomes incarcerated. • Symptoms of hiatal hernia present as GERD. It may also present as chest pain mimicking angina. GERD in patients with a hiatal hernia can result from – The backward flow of gastric acid into the esophagus and trapping into the hernia sac during swallowing. – Contraction of the crural diaphragm during inspiration leads to a compartmentalization of the stomach between the LES and the diaphragm • Any sudden increase in intra-abdominal pressure will increase the LES pressure by acting on the portion of the LES below the diaphragm. • Diabetic gastroparesis and gastric ulcers may delay gastric emptying leading to worsening of symptoms in hiatal hernia patients. • Certain drugs that may slow gastric emptying, including opioids, beta-blockers, tricyclic antidepressants, and aluminum hydroxide antacid may increase the risk of aspiration in hiatal hernia patients.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The goal of anesthesia management is to prevent aspiration; appropriate techniques prior to induction and emergence should be considered. • An open or laparoscopic Nissen fundoplication may be performed to surgically repair a hiatal hernia. While the results are comparable to an open procedure, laparoscopic fundoplication may decrease postoperative pain and hospital stay while providing a more rapid return to work and better cosmetic results. Downsides of the surgery include a recurrence of symptoms, swallowing difficulties, failure, and increased bloating and discomfort.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Indigestion, epigastric pain, nausea and vomiting, regurgitation, and chest pain. In patients with concomitant cardiovascular diseases, chest pain of cardiac origin needs to be ruled out before the treatment of the GERD. • Chronic aspiration may present as an acid taste or sensation of refluxing liquid into the mouth or paroxysms of coughing and/or wheezing.

History

Quality of heart burn and inciting factors Signs/Physical Exam

Epigastric tenderness may be present in patients with severe acid reflux symptoms. TREATMENT HISTORY

Failed Nissen fundoplication MEDICATIONS

• H2-receptor antagonists: Decrease gastric acid secretion for both gastric pH and volume. • Proton pump inhibitors are the most powerful medications for GERD. They block the final steps in the hydrogen ion secretion by the parietal cells and raise stomach pH • Antacids: Usually raise the pH of the gastric fluid, but at the same time increase gastric volume. • Metoclopramide: Shortens gastric emptying time, increases LES tone, and is an antiemetic. It does not affect gastric pH. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Complete blood count, electrolytes, urea, and creatinine • CXR; if aspiration is suspected. • Barium radiography • Gastric endoscopy examination

CONCOMITANT ORGAN DYSFUNCTION • GERD • Chronic aspiration

CIRCUMSTANCES TO DELAY/CONDITIONS

If the patient is believed to have a “full stomach” due to recent food intake, and the surgical procedure is elective, the operation should be postponed. CLASSIFICATIONS

• Sliding hiatal hernia (Type I) • Paraesophageal hernia (Types II, III, and IV)

TREATMENT PREOPERATIVE PREPARATION Premedications

• GERD medications should be continued until surgery. • Antacids are immediately effective in decreasing gastric acidity, but may increase gastric volume slightly.

• Metoclopramide can be administered to decrease the gastric volume.

Special Concerns for Informed Consent Risk for aspiration

INTRAOPERATIVE CARE Choice of Anesthesia

• For general anesthesia, quick control of the airway with an endotracheal tube (rapid sequence induction) is indicated to prevent refluxing of gastric content into the oropharynx and lungs. If a difficult intubation is anticipated, intubation should precede induction (awake fiberoptic intubation). • General anesthesia delivered via a mask or laryngeal mask airway is contraindicated. • For monitored anesthesia care (MAC), avoid oversedation which can lead to a loss of the gag reflex and aspiration. • Regional anesthesia with minimal sedation may be considered, if it is practical for the procedure.

Monitors

Standard ASA monitors

Induction/Airway Management

• Suction should be checked and immediately available. • Rapid sequence induction is indicated in patients with symptomatic hiatal hernia, without a difficult airway. Despite the need for rapidly securing the airway, adequate time needs to be given to allow for the onset of induction agents and neuromuscular blockade to avoid coughing, straining, and bucking (can cause strong forceful movement of stomach contents upwards). • Succinylcholine 1.5 mg/kg or rocuronium 1–1.2 mg/kg is usually used in addition to the induction agents, including propofol, thiopental, or etomidate. • Sellick’s maneuver (firm pressure over cricoid cartilage prior to induction) is used to collapse the esophagus and prevent gastric content reaching the oropharynx and lungs. • Consider placing the patient in reverse Trendelenburg to reduce passive reflux (gravity). • A wide assortment of cuffed endotracheal tubes and laryngoscopy blades should be prepared in advance to facilitate quick intubation.

Maintenance

• An orogastric tube may be gently inserted to suction any stomach contents after endotracheal intubation, and left in place until the end of the procedure. • Short-acting anesthetics should be considered to enhance rapid wakening of patients • Nondepolarizing muscle relaxants should be used cautiously to avoid persistent postoperative paralysis.

Extubation/Emergence

• Removal of the orogastric tube while on suction. • Ensure full recovery or reversal if muscle relaxants are used.

• Patients should be extubated only after they are fully awake and regain the ability to protect their airway. • Consider placing the patient in a reverse Trendelenburg position to reduce the incidence of passive reflux. • Prophylaxis for postoperative nausea and vomiting.

POSTOPERATIVE CARE BED ACUITY

Depends on the surgical procedure, patient comorbidities, and intraoperative events. If pulmonary aspiration is suspected, a higher level of care is warranted to monitor for respiratory dysfunction and hypoxia MEDICATIONS/LAB STUDIES/CONSULTS

Administration of narcotics for postoperative pain should be done carefully, as they may delay gastric emptying as well as inhibit the gag reflex (from oversedation). COMPLICATIONS

• Perioperative aspiration: Treat with supportive measures including suctioning of the oropharynx, protection of the airway with endotracheal intubation, supplemental oxygen, and ventilatory support in severe cases as well as bronchoscopy and pulmonary lavage. • Additional surgical complications of Nissen fundoplication include pneumothorax, injury to the stomach, esophagus, and liver in addition to bleeding and infection.

REFERENCES

1. Schieman C, Grondin SC. Paraesophageal hernia: Clinical presentation, evaluation, and management controversies. Thorac Surg Clin. 2009;19(4):473–484. 2. Koerber JP, Roberts GE, Whitaker R, et al. Variation in rapid sequence induction techniques: Current practice in Wales. Anesthesia. 2009;64(1):54–59. 3. Neumann L, Poulton B, Ridley S. Life-threatening complications of hiatus hernia. Anaesthesia. 1999;54(1):93–94. See Also (Topic, Algorithm, Electronic Media Element) • Gastric esophageal reflux disease • Aspiration

CODES ICD9 • 553.3 Diaphragmatic hernia without mention of obstruction or gangrene • 553.3 Hiatal hernia ICD10

K44.9 Diaphragmatic hernia without obstruction or gangrene

CLINICAL PEARLS

• In patients with a diagnosed hiatal hernia, perioperative care should be tailored to reduce the incidence of aspiration. • Aspiration may lead to pneumonitis or pneumonia, both potentially fatal illnesses. • Special care must be taken when using transesophageal echocardiography in patients who may have hiatal hernia, because there is an increased risk of esophageal perforation.

HICCUPS

Dierk A. Vagts, MSc, DEAA, EDIC

BASICS DESCRIPTION

• Hiccups are caused by intermittent, involuntary contractions of the diaphragm and inspiratory muscles. The characteristic sound arises from very fast shutting of the glottis (1). • Perioperatively, brief bouts of hiccups are most often precipitated by medications, irritation of the diaphragm, or gastric distention from swallowing blood, gas, or debris. • Chronic or intractable hiccups can adversely affect the quality of a patient’s life by causing fatigue, sleep disorders, dehydration, depression, anorexia and weight loss, and death (from the underlying disorder) (2).

EPIDEMIOLOGY Incidence

1–4% of patients develop hiccups with the placement of a laryngeal mask airway (LMA). Prevalence

No data available Morbidity

Risk of • Hyperventilation during anesthesia • Aspiration during induction, extubation, or emergence • Wound dehiscence • Reflux esophagitis • Interference with the surgical field (2) Mortality

Not known

ETIOLOGY/RISK FACTORS

• Etiology might be organic, idiopathic or psychogenic. • Anesthetic: Induction medications; LMA insertion (expansion of the oropharyngeal and/or upper esophageal space may stimulate the vagus nerve); carbon dioxide (laparoscopic procedures); gastric distention (2) • Gastrointestinal: Hepatic failure, cholelithiasis, pancreatitis, hiatal hernia, gastroesophageal reflux disease (atypical manifestation) (3) • Psychiatric: Anorexia, hysteric neurosis, personality disorder traits • Central nervous system: Ventriculoperitoneal shunt, multiple sclerosis, arteriovenous malformation, epidural or subdural hematoma, traumatic brain injury, hyperdopaminergic

states • Cardiac: Deviant cardiac pacemaker electrodes, myocardial infarction, pericarditis • Pulmonary: Lung contusion, bronchial carcinoma, bronchitis, pleural empyema, asthma • Head and Neck: Neck tumors • Renal: Insufficiency, uremia • Metabolic: Hypocalcemia, hyponatremia (4)

PHYSIOLOGY/PATHOPHYSIOLOGY

• Not completely understood; there are several hypotheses to explain the phenomenon of hiccups. – Protective mechanism to reduce the intake of large amounts of nutrition – Support the development of the respiratory system in utero – Phylogenetic residual phenomenon of gill breathing (2) • There are three general components – Afferent limb: Vagal, phrenic, and sympathetic (T6–T12) branches – Central processor: Spinal cord (C3–C5), brain stem, midbrain. Processing is believed to be mediated by several poorly defined neurotransmitters, including GABA and dopamine – Efferent limb: Phrenic nerve, recurrent laryngeal nerve, accessory nerves to the diaphragm, glottis, anterior scalenes, external intercostals, lower esophageal sphincter muscles (2)

PREVENTATIVE MEASURES Not known

DIAGNOSIS • Self-limited hiccups are often from peripheral sources such as the epigastrium, and occur secondary to gastric distention, irritation, or reflux. • Intractable hiccups are often from central mechanisms such as CNS disorders.

DIFFERENTIAL DIAGNOSIS

In the case of intractable hiccups (longer than 1 month), the infiltration of a tumor into the phrenic nerve must be excluded.

TREATMENT • Perioperative hiccups are usually self-limited and resolve without treatment. If they interfere with the procedure or exceed 2 hours, treatment may be considered. There is currently no evidence-based treatment. Options can be divided into pharmacological, nonpharmacological, and invasive measures. • Pharmacological – Intraoperatively Ephedrine 5–10 mg IV; may act on central receptors Neuromuscular blocking drugs, if appropriate

Gastric acid reducers such as proton pump inhibitors and H2 blockers may be effective

when hiccups are the result of GERD. Metoclopramide; aids with gastric emptying Atropine 0.5 mg IV; may act directly on the esophagus by decreasing intraesophageal pressure and hence peripheral mechanoreceptor-mediated reflexes, or indirectly on the CNS via enhancement of sympathetic nerve activity (5). Antidopaminergics such as chlorpromazine 25–50 mg IV or IM, droperidol, or haloperidol; have inhibitory effects at the hypothalamus. Propofol 0.25–0.5 mg/kg IV; titrate to effect Ketamine (6) Lidocaine 1 mg/kg IV; may follow with a continuous infusion. Serotonin-5HT-1-A-receptor antagonists; receptors are located in the medulla in regions involved with respiratory control. Inhibition shortens inspiratory discharges (8). – Postoperatively Ephedrine, gastric acid reducers, metoclopramine, atropine, antidopaminergics, propofol, ketamine, lidocaine, serotonin-5HT-1-A-receptor antagonists may be appropriate Baclofen 5 mg PO TID; a GABA agonist, typically used to treat spastic movement by decreasing excitability and synaptic transmission at the level of the spinal cord. It is believed that a similar mechanism is responsible for decreasing the hiccup reflex. Gabapentin 300 mg PO TID; slow onset and more appropriate for chronic or intractable hiccups (4,7). Carvedilol 6.25 mg QID; unclear mechanism; may be an alternative to antidopaminergic medications (9). Antiepileptic drugs; phenytoin inhibits the transmission of motor activity; valproic acid increases the function of GABA; carbamazepine blocks post-tetanic potentiation. For psychogenic hiccups: Try distraction by assigning a new task • Nonpharmacological intraoperative and postoperative (2) – Increase PaCO2 by Holding or decreasing ventilation Rebreathing CO2

– Reduction of Hering–Breuer reflex by inflating and keeping the lungs extended with Continuous positive airway pressure (CPAP) (10) Valsalva maneuver – Induction of contrairritation to inhibit the reflex for hiccups with a different reflex Traction on the tongue Bilateral orbital compression Carotid massage Rectal massage Stimulation of nasopharynx with a catheter or nasopharyngeal airway (11) Gastric lavage The Heimlich maneuver is not recommended. • Invasive measures for intractable or chronic hiccups – Paravertebral block C3–C5, right or left side – Cervical peridural anesthesia at C7 with 8 mL lidocaine 1.5% (12)

– Phrenic nerve block Electrical nerve stimulation between the sternocleidomastoid and anterior scalene muscle (may perform unilaterally or bilaterally) Surgical blockade (13,14) – Recurrence of hiccups is common after a single-injection technique for phrenic nerve blockade; thus a catheter technique should be considered. All techniques try to interrupt the neural pathway (15).

FOLLOW-UP There is no evidence for any of the possible treatment options. However, as it is necessary to stop hiccups to reduce the risk of aspiration during general anesthesia, patients may benefit from sharing of the events. CLOSED CLAIMS DATA Not available

REFERENCES

1. Fass R. Stimulusand site specific induction of hiccups in the oesophagus of normal subjects. Gut.1997;41:590–593. 2. zibor-Krisen U, Devide A, Hoetzel A, et al. Persistent intractable hiccup in the perioperative period. AINS. 2008;43:674–676. 3. Becker DE Nausea, vomiting, and hiccups: A review of mechanisms and treatment. Anesth Prog. 2010;57(4):150–156. 4. Tegeler ML, Baumrucker SJ. Gabapentin for intractable hiccups in palliative care. Am J Hosp Palliat Care. 2008;25(1):52–54. 5. Kanaya N, Nakayam M, Kanaya J, et al. Atropine for the treatment of hiccup after laryngeal mask insertion. Anesth Analg. 2001;93(3):791–792. 6. Shants RT. Ketamine for the treatment of hiccups during and following anesthetic. A preliminary report. Anesth Analg. 1973;52:822–824. 7. Alonso-Navarro H, Rubio L, Jimenez-Jimenez F. Refractory hiccup: Successful treatment with gabapentin. Clin Neuropharmacol. 2007;30:186–187. 8. Takahashi T, Murata T, Omori M, et al. Successful treatment of intractable hiccups with serotonin (5-HT)1A receptor agonist. J Neurol. 2004;251:486–487. 9. Stueber D, Swartz CM. Carvedilol suppresses intractable hiccups. J Am Board Fam Med. 2006;19:418–421. 10. Saitto C, et al. Treatment of hiccups by continuous positive airway pressure (CPAP) in anesthetized subjects. Anesthesiology. 1982;57:345. 11. angar D. Elimination of hiccups with a nasopharyngeal airway. J Clin Anesth. 1992;4:86.

12. Sato S. Cervical epidural block can relieve postoperative intractable hiccups. Anesthesiology. 1993;78:1184–1186.

13. Okuda Y. Use of a nerve stimulator for phrenic nerve block in treatment of hiccups. Anesthesiology. 1998;88:525–527. 14. Renes SH, van Geffen GJ, Rettig HC, et al. Ultrasound-guided continuous phrenic nerve block for persistent hiccups. Reg Anesth Pain Med. 2010;35:455–457.

15. Lierz P, Felleiter P. Anesthesia as therapy for persistent hiccups. Anesth Analg. 2002;95:494–495.

ADDITIONAL READING

• Kranke P, Eberhart LH, Morin AM, et al. Treatment of hiccup during general anaesthesia or sedation: A qualitative systematic reviews. EJA. 2003;20:239–244. • Straus C, Vasilakos K, Wilson RJA, et al. A phylogenetic hypothesis for the origin of hiccough. Bioesssays. 2003;25:182–188.

See Also (Topic, Algorithm, Electronic Media Element) • Tardive dyskinesia • Laryngeal mask airway

CODES ICD9 786.8 Hiccough ICD10 R06.6 Hiccough

CLINICAL PEARLS

• Hiccups are a sudden contraction of the diaphragm and intercostal muscles followed immediately by laryngeal closure. • Mostly occurs during inspiration and is inhibited by elevations in PaCO2.

HOFMANN ELIMINATION Corey C. Downs, MD

BASICS DESCRIPTION

• The chemist August Wilhelm von Hofmann (1818–1892) was the first to synthesize quaternary amines, a cationic salt in which the nitrogen atom is bound to four groups and carries a positive charge (NR4+). When subjected to the harsh conditions of basic solutions and high temperatures, quaternary amines will undergo a chemical reaction, Hofmann degradation, breaking into two fragments–a tertiary amine and an alkene.

• If a drug could undergo a similar spontaneous degradation reaction under the milder, physiological conditions that exist within the body, it would allow for organ-independent and enzyme-independent termination of its effect. • Hofmann elimination describes the mechanism by which some drugs based on a quaternary amine structure can undergo spontaneous degradation in vivo to inactive metabolites; it is a temperature and pH-dependent process. At this time, only the neuromuscular blocker atracurium and one of its isomers, cisatracurium, appear to harness this effect.

PHYSIOLOGY PRINCIPLES

• Quaternary amines. Prepared by alkylation of tertiary amines in a process called quaternization. The newly added alkyl group is typically a large, weak base, thus making it a good “leaving” group under the appropriate conditions (high temperatures and a strong basic solution). • Hofmann elimination – Breakdown of quaternary amines. Can occur under physiologic conditions: pH = 7.4, temperature = 37°C – Temperature-dependent metabolism – pH-dependent metabolism – Organ-independent metabolism – Enzyme-independent metabolism • Currently available drugs. Despite the benefits of spontaneous degradation under physiologic conditions, the arsenal of anesthetic medications undergoing Hofmann

elimination to a clinically significant degree is limited to two neuromuscular blockers. – Neuromuscular blocking drugs share a common structure, a quaternary ammonium group that is essential for their function (binding to nicotinic acetylcholine receptors). – Atracurium besylate was specifically chosen to take advantage of Hofmann elimination. The beta-positional relationship between its nitrogen and carbonyl group results in a molecular structure that allows Hofmann elimination to occur under physiological conditions (1). A small portion of atracurium also undergoes metabolism via ester hydrolysis. Its side effects of histamine release (hypotension, tachycardia, bronchospasm), as well as the potentially toxic effects of the tertiary amino alkaloid, laudanosine, have limited its clinical use.

– Cisatracurium besylate is the R, cis-R’-isomer of atracurium. More potent Lacks or has significantly less histamine release and related side effects

Although elimination results in the production of laudanosine, the amount is significantly less than with atracurium.

DISEASE/PATHOPHYSIOLOGY

• Liver and renal disease. Because of its organ independence, the rate of Hofmann elimination is essentially unaffected in these disease states. – The dose requirements and recovery profiles of atracurium and cisatracurium in liver failure patients are not significantly different from those in patients with normal liver function (2). – No significant difference was found in recovery parameters of patients with renal failure receiving atracurium when compared to normal controls (3). • Temperature derangements. Hofmann elimination will accelerate with increasing

temperature, while slowing for decreasing temperature. However, the clinical significance of this change within ranges compatible with life is minimal or only requires minor dose adjustments. – Cisatracurium’s duration of action can be prolonged while on hypothermic cardiopulmonary bypass (4). – Hyperthermic states, as seen in malignant hyperthermia, hyperthyroidism, or hyperthermic intraperitoneal chemotherapy, may cause a higher clearance of atracurium (5). – Slow infusions of either of these drugs through hot-lines containing basic carrier solutions theoretically could lead to accelerated breakdown. • pH derangements. Hofmann elimination will accelerate as the body becomes more alkaline, while slowing in acidic conditions. Over the narrow pH range compatible with life this effect is likely of little significance. • Genetic variations. As a nonenzymatic process, Hofmann elimination is unaffected by genetic variations and mutations in enzymes. For example, unlike succinylcholine, cisatracurium is not affected by atypical plasma cholinesterase. • Age does not appear to affect Hofmann elimination. Obesity does not change the rate of Hofmann elimination.

PERIOPERATIVE RELEVANCE

In patients with renal or liver impairment, there is often concern over prolongation of a drugs effect. For neuromuscular blockers this unpredictable duration can lead to an inability to extubate, case delays, and airway compromise. Because they are processed primarily by Hofmann elimination, atracurium and cisatracurium can be part of an anesthetic plan with minimal or no change in dose requirements regardless of the patient’s pathology.

REFERENCES

1. Stenlake JB, Waigh RD, Urwin J, et al. Atracurium: Conception and inception. Br J Anaesth. 1983;(Suppl 1):3S–10S. 2. De Wolf AM, Freeman JA, Scott VL, et al. Pharmacokinetics and pharmacodynamics of cisatracurium in patients with end-stage liver disease undergoing liver transplantation. Br J Anaesth. 1996;76:624–628. 3. Fahey MR, Rupp SM, Fisher DM, et al. The pharmacokinetics and pharmacodynamics of atracurium in patients with and without renal failure. Anesthesiology. 1984;61:699–702. 4. Withington D, Menard G, Varin F. Cisatracurium pharmacokinetics and pharmacodynamics during hypothermic cardiopulmonary bypass in infants and children. Pediatr Anesth. 2011;21:341–346. 5. Jonker G, Hoogenboom LJ, van Ramshorst B, et al. Atracurium during induced hyperthermia. J Anesth. 2009;23(3):442-444.

ADDITIONAL READING

• Kisor D, Schmith V, Wargin W, et al. Importance of the organ-independent elimination of cisatracurium. Anesth Analg. 1996;83:1065–1071.

• Prielipp R, Coursin D, Scuderi P, et al. Comparison of the infusion requirements and recovery profiles of vecuronium and cisatracurium 51W89 in intensive care unit patients. Anesth Analg. 1995;81:3–12.

See Also (Topic, Algorithm, Electronic Media Element) • Neuromuscular blockade • End-stage liver disease • Chronic renal failure • Metabolic acidosis

CLINICAL PEARLS

• Hofmann elimination is a nonenzymatic, organ-independent degradation of quaternary amines that for some drugs can occur at physiological temperatures and pH thus terminating their clinical effect. • Atracurium and cisatracurium primarily are inactivated via Hofmann elimination leading to a more predictable duration of action with minimal or no dose adjustment in patients with liver failure, renal impairment, or genetic variations in enzymes. • Perhaps future research will develop additional drugs to take advantage of Hofmann elimination, thus extending the options and safety margins for these patient populations.

HYPERBARIC OXYGEN THERAPY Shawn T. Simmons, MD

BASICS DESCRIPTION

• Hyperbaric oxygen (HBO) therapy is defined as the breathing of 100% oxygen inside a pressure vessel at greater than one atmosphere absolute (ATA). – Application of 100% oxygen to isolated body parts or breathing oxygen at surface (sea level) pressure is not HBO. • Terminology is often marine related due to the close relationship between hyperbarics and diving: – Dive = treatment – Depth = treatment pressure – Descent = compression of the chamber – Ascent = decompression of the chamber • There are two general types of chambers: – Monoplace Capacity limited to one patient at a time Generally compressed with oxygen Limited patient access. Monitors and IVs must enter chamber through a specially designed “pass-through.” Less expensive to purchase and run than multiplace units – Multiplace Capacity for more than one patient at a time Generally compressed with air; oxygen is delivered to the patient via hood, mask, or other airway (endotracheal tube, tracheostomy tube) Most often have an inside attendant that is compressed with the patient(s). This allows for easier patient care and manipulation of ventilators, IVs, etc., but requires the use of dive tables to avoid decompression illness (“the bends”) in the attendant. More expensive to purchase (each is custom built for the specific location), maintain, and staff • In general, a hyperbaric oxygen treatment consists of breathing 100% oxygen for 60–120 minutes at pressures of 2.0–2.4 ATA. The pressure, duration, and number of treatments are varied depending on the disease being treated and the chamber type used (multiplace chamber are often able to achieve higher pressures than monoplace chambers). PHYSIOLOGY PRINCIPLES

• Boyle’s gas law: The volume of a gas is inversely proportional to its pressure when the temperature is held constant. – Increased pressure directly shrinks gas bubbles in the blood and tissues. – Patients must equalize the pressure in the middle ear to the external environment via the

Eustachian tube or risk eardrum rupture. – An untreated pneumothorax may transform into a tension pneumothorax on decompression as the extrapleural gas in the chest cavity expands. – Implanted devices, such as pacemakers, must be certified for hyperbaric environments as the change in pressure can result in malfunction and/or damage. – Air must be eliminated from IV tubing and bags to avoid air embolism on decompression. – Drains must be open to air during compression and decompression to allow equalization of pressure. – Endotracheal tube cuffs must be filled with saline or constantly adjusted during descent and ascent. • Henry’s gas law: The partial pressure of a gas dissolved in a liquid is directly proportional to the pressure of the gas on the surface of the liquid. – Increased ambient pressure and 100% oxygen increase the amount of oxygen dissolved in the plasma. Oxygenation of ischemic tissues Promotes angiogenesis Increased diffusion gradient to enhance elimination of inert gases Bacterial control via direct killing of anaerobic species and enhanced leukocyte function Hyperoxia causes arterial vasoconstriction; there can be a ∼10% increase in systemic vascular resistance under hyperbaric conditions. CNS oxygen toxicity can provoke seizures in susceptible patients. Pulmonary oxygen toxicity can result in pulmonary fibrosis during prolonged exposures.

ANATOMY

• Oxygen is delivered to tissues via the bloodstream, so a minimum capillary density is needed to observe a benefit. • Tissue oxygenation decreases geometrically as distance from the capillary increases.

DISEASE/PATHOPHYSIOLOGY

• Only certain diseases and conditions have been approved as appropriate for HBO therapy by the Undersea and Hyperbaric Medicine Society (1)[A] • Air or gas embolism – Air is introduced into the vascular system, usually via medical devices or trauma. – Hyperbaric effects Increased pressure directly shrinks gas bubbles in the bloodstream and tissues. Elevated oxygen tension provides an enhanced diffusion gradient for the elimination of inert gas. Therapy: Depending on severity, prolonged treatments at high pressures (3.0–6.0 ATA) may be needed to resolve symptoms. • Carbon monoxide (CO) poisoning – CO is produced from incomplete combustion – CO has ∼200 times the affinity for hemoglobin (Hgb) than O2 and is also a direct cellular toxin (can cause acute cardiac and acute/delayed neurological dysfunction). – Hyperbaric effects HBO greatly accelerates the elimination of CO from the blood.

Can help prevent delayed neurologic sequela (2)[A]. Therapy: A short series (1–3) of higher pressure (2.8–3.0 ATA) treatments. • Clostridial myositis and myonecrosis (gas gangrene) is caused by organisms in the clostridia family. – Clostridia organisms secrete exotoxins that impair host defenses and produce the toxic host reaction. – Hyperbaric effects Inhibits bacterial growth (clostridia is a facultative anaerobe and is not directly killed by oxygen). Stops alpha-toxin production (the exotoxin produced by clostridia that is most associated with morbidity and mortality). Therapy: A short series of treatments, the first being at higher pressure (3.0 ATA), until the patient stabilizes. The initial three treatments are delivered in 24 hours, then twice daily after that. • Crush injury, compartment syndrome, and other types of acute ischemia – Trauma reduces blood flow to tissues, which then become ischemic, resulting in vasogenic edema, further compromising blood flow and tissue oxygenation. – Hyperbaric effects Oxygenates ischemic tissues Reduces compartment edema due to decreased inflow due to arteriolar constriction from hyperoxia and unchanged venous outflow. Therapy: A short series of twice daily treatments at 2.0–2.4 ATA until the acute ischemia is resolved. • Decompression sickness – Breathing air at increased ambient pressures (such as when scuba diving) causes increased levels of nitrogen to be dissolved in the tissues and blood. – During decompression/ascent, this nitrogen comes out of solution and forms bubbles in the tissues and bloodstream if adequate decompression time is not allowed (i.e., nitrogen comes out of solution faster than it can be eliminated through the lungs). – These bubbles lodge in capillaries, resulting in decreased blood flow (joint pain, myocardial and neurologic ischemia, V/Q mismatch, etc.), platelet aggregation, and activation of the complement cascade. – Hyperbaric effects Shrinks bubbles in plasma and tissues. Enhanced diffusion gradient for inert gases. Therapy: Depending on severity, prolonged treatments at high pressures (3.0 ATA) may be needed to resolve symptoms. • Enhancement of healing in selected problem wounds – Problem wounds often fail to heal due to inadequate oxygen delivery secondary to impaired microvascular injury, such as in diabetes. – Transcutaneous oxygen monitoring can be used to assess potential benefit of hyperbaric therapy (3)[B]. – Hyperbaric effects Promotes angiogenesis

Bacterial control Oxygenate ischemic tissues Enhanced fibroblast activity Therapy: 20–30 daily treatments at 2.0–2.4 ATA. • Exceptional anemia – Massive bleeding without the possibility of transfusion (religious beliefs, difficult crossmatch). – Hyperbaric effects At 3.0 ATA on FiO2 1.0, enough oxygen can be dissolved in plasma to support basic

metabolic function without hemoglobin. Therapy: Short series of high pressure (2.8–3.0 ATA) treatments until blood products are available or until Hgb has increased to acceptable levels. Interval between treatments should be guided by evidence of recurring ischemia (ECG change, acidosis, etc.). • Intracranial abscess – Adjunctive HBO therapy indicated for patients with: Multiple abscess or those in deep tissues or dominant locations, immunocompromised, contraindications to surgery, or no response to standard treatment. – Hyperbaric effects Bacterial control Oxygenate ischemic tissues Therapy: Once to twice daily treatments at 2.0–2.4 ATA. Optimal duration of treatments unknown. • Necrotizing soft tissue infections – Multiorganism, rapidly spreading infections that often tract along fascial layers. – Hyperbaric effects Bacterial control Oxygenation of ischemic tissues Therapy: Short series twice daily treatments at 2.0–2.4 ATA • Osteomyelitis (refractory) – Infection of bone that is difficult to clear due to impaired blood flow and ischemic environment. – Hyperbaric effects Bacterial control Oxygenation of ischemic bone Enhanced osteoclast function Therapy: 20–30 (or more) daily treatments at 2.0–2.4 ATA. • Delayed radiation injury (soft tissue and bony necrosis) (4)[B] – Radiation therapy causes endovascular injury that results in decreased capillary density. – Capillary density continues to decrease over time, even after radiation therapy ends, resulting in ischemic tissues in the irradiated field. – This ischemia can result in tissue breakdown either spontaneously or after trauma, including surgery. – Hyperbaric effects Promotes angiogenesis

Bacterial control Oxygenates ischemic tissues Therapy: 20–30 daily treatments at 2.0–2.4 ATA Marx protocol: Used in the case of osteoradionecrosis of the jaw when a tooth extraction is planned in a previously irradiated area. The patient is given 20 treatments prior to the extraction and 10 treatments postextraction. • Skin grafts and flaps – Compromised blood flow to grafts and flaps can result in ischemia and loss of the graft. – Hyperbaric effects Oxygenation of ischemic tissues Promotes angiogenesis Therapy: A short series of twice daily treatments at 2.0–2.4 ATA until the acute ischemia is resolved. • Thermal burns – Thermal injury impairs oxygenation via vascular coagulation and edema. – Hyperbaric effects Oxygenation of ischemic tissues Therapy: A series of treatments at 2.0–2.4 ATA.

PERIOPERATIVE RELEVANCE

• Hyperbaric treatment performed immediately prior to debridement can help differentiate viable from dead tissue. • Myringotomies will need to be performed on intubated patients and others who are unable to clear their ears (equalize the pressure in the inner ear with the external environment).

EQUATIONS

• Boyle’s law: P1V1 = P2V2; where P is pressure and V is volume • Alveolar oxygen equation – PAO2 = FiO2(PB – PH2O) – (PaCO2/RQ) PaO2 = alveolar oxygen pressure.

PB = barometric pressure (mm Hg).

PH2O = water vapor pressure (usually 48 mm Hg). RQ = respiratory quotient (usually 0.8) 21% O2 at 1 ATA: PaO2 = 100 mm Hg

100% O2 at 3 ATA: PaO2 = 1,500 mm Hg

• Arterial oxygen content – CaO2 = 1.34(Hgb)(%sat) + (0.003)(PaO2)

1.34(Hgb)(%sat) = oxygen attached to Hgb (0.003)(PaO2) = oxygen dissolved in plasma.

At 3 ATA on 100% oxygen, 5 mL/dL of oxygen can be dissolved in the plasma, which can support resting metabolism. • 1 ATA = 33 feet of seawater = 14.2 psi

REFERENCES

1. Gesell LB, Chairman and Editor. Hyperbaric Oxygen Therapy Indications: The Hyperbaric Oxygen Committee Report, 12th edn. Durham, NC: Undersea and Hyperbaric Medicine Society, 2008. 2. Weaver LK, et al. Hyperbaric oxygen for acute carbon monoxide poisoning. N Engl J Med. 2002;347(14):1057–1067. 3. Fife CE, et al. The predictive value of transcutaneous oxygen tension measurement in diabetic lower extremity ulcers treated with hyperbaric oxygen therapy: A retrospective analysis of 1,144 patients. Wound Repair Regen. 2002;10(4):198–207. 4. Feldmeier JJ. Hyperbaric oxygen for delayed radiation injuries. Undersea and Hyperb Med. 2004;31(1):133–145.

ADDITIONAL READING

• Clark RE. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: A randomized and controlled double-blind crossover trial with long-term follow-up. Int J Radiat Oncol Phys. 2008;72(1):134–143. • Kindwall EP, Whelen HT. Hyperbaric Medicine Practice, 3rd edn. Best Publishing Company, Flagstaff, Arizona, 2008. • www.UHMS.org See Also (Topic, Algorithm, Electronic Media Element) • PaO2

• Partial pressure • Carbon monoxide poisoning

CLINICAL PEARLS

• For acute indications (CO, crush injury, failing graft, etc.), benefits are decreased with increased delay in the start of treatments. • In the case of delayed radiation injury (osteoradionecrosis or soft-tissue radionecrosis), it takes ∼8 treatments to start to see clinical evidence of angiogenesis, which becomes maximized at roughly 80% of preradiation levels at ∼20 treatments. • Wounds must have an element of hypoxia (diabetes, radiation injury, trauma, etc.) to be helped by hyperbaric oxygen. – Hyperbaric treatments will not help normally oxygenated wounds heal faster. – Wounds that are not healing for other reasons (pressure, venous insufficiency, etc.) will not benefit from HBO therapy. • Contraindications to HBO therapy: – Untreated pneumothorax – Concurrent chemotherapy with adriamycin (heart failure in hyperoxic environment) or cisplatinum (wound breakdown in hyperoxic environments). – Concurrent or prior exposure to bleomycin (reports of acute pulmonary fibrosis when exposed to high oxygen concentrations. No known safe interval between treatment with

bleomycin and exposure to hyperoxia). • There is little-to-no evidence in the peer-reviewed literature to support the use of HBO to treat chronic CNS injuries/dysfunction (stroke, cerebral palsy, autism, etc.).

HYPERGLYCEMIA

Michael S. Green, DO Poovendran Saththasivam, MD

BASICS DESCRIPTION

• Hyperglycemia (>180–200 mg/dL) is common in diabetics as well as critically ill patients without diabetes. It can result from – Insulin deficiency – Insulin receptor resistance – Excess of glucagon – Glucose over-administration • Stress-induced hyperglycemia compared to diabetic hyperglycemia has been reported to increase the length of hospital stay and in-hospital mortality. EPIDEMIOLOGY Prevalence

• Approximately 23 million patients have diabetes. • Type 2 diabetes is seen in ~12.9% of people older than 20 years of age.

Morbidity

Diabetes is associated with a higher risk of acute myocardial infarction, stroke, and heart failure Mortality

• Three-fold increase in mortality in patients with hyperglycemia following acute myocardial infarction. • Poor outcome has been observed in non-diabetic patients with acute stroke and stressinduced hyperglycemia. ETIOLOGY/RISK FACTORS

• Underlying diabetes mellitus (DM) • Inadequate insulin dosing in diabetics • Concurrent medical illness: Stroke, acute myocardial infarction, trauma, sepsis, hypoxia • Medication side effect • Obesity

PHYSIOLOGY/PATHOPHYSIOLOGY

• In healthy individuals, the blood glucose level is closely regulated by insulin production, hepatic glucose uptake, and production. • Insulin actions include

• Increased transport of glucose, potassium, and amino acids into cells • Protein synthesis • Glycogen synthesis • Inhibition of gluconeogenesis • Counterregulatory hormones (cortisol, catecholamine, growth hormone) decrease peripheral glucose uptake, inhibit hepatic glucose uptake, and increase hepatic gluconeogenesis and glycogenolysis. • Hyperglycemia • Insulin deficiency (or insulin resistant states) can result in fat catabolism and increased formation of acetyl CoA. Acetyl CoA will then form ketone bodies. • Immune function. Impairs phagocytic function (adherence and chemotaxis) of neutrophils and monocytes. Believed to be secondary to elevated cytosolic calcium in polymorphonuclear (PMN) leukocytes that result in reduced ATP synthesis as well as reduced superoxide formation in leukocytes. • Fluid balance. Glycosuria promotes dehydration and various electrolyte imbalances. It can cause serum hypertonicity and acidosis. • Cardiovascular system. Hyperglycemia can increase systolic and diastolic BP, prolong the QTc, and elevate catecholamine levels. Hyperglycemia can increase platelet activation and adhesion, leading to thrombosis; as well as inflammatory markers such as TNFα, IL-6, and IL-18. Studies have also demonstrated that it affects ischemic preconditioning of the heart and reduced coronary collateral blood flow. • Central nervous system (CNS). The penumbra area that surrounds the ischemic zone in the brain is at increased risk for further infarction in hyperglycemic states because of the ensuing acidosis and high lactate levels. High levels of lactate can damage astrocytes, endothelial cells, and neurons. • Glycemic control. Studies have yielded varying results. • In critically ill surgical patients, tight glycemic control using intensive insulin therapy (between 80 and 110 mg/dL) has shown improved outcomes. • However, subsequent studies in the medical intensive care unit (ICU) have failed to show similar benefits in all patients and more hypoglycemic episodes observed in patients with more than 3 days of hospital stay. • Furthermore, glucose variability has been shown to be more important than maintaining the glucose level in a certain range. Fluctuation of blood glucose can cause increased apoptosis, cytokine expression, and oxidative stress markers.

PREVENTATIVE MEASURES

Surgical and anesthetic techniques that can minimize hyperglycemia responses: • Minimally invasive surgery. The stress of surgery can reduce insulin sensitivity and the release of counterregulatory hormones that can cause hyperglycemia. • Avoid hypovolemia which can trigger a hyperosmolar hyperglycemic nonketotic (HHNK) state (severe hyperglycemia often >600 mg/dL, hyperosmolarity often >320 mOsm/kg, glycosuria with worsening hypovolemia, and central nervous system depression). Dehydration combined with baseline impaired insulin production can further decrease insulin levels and worsen hyperglycemia (compared to diabetic ketoacidosis, HHNK has

sufficient levels of insulin to prevent lipolysis and ketone production). • Prevent nausea and vomiting (can lead to hypovolemia and electrolyte imbalances). Identify patients at risk and avoid drugs with emetic properties (if possible) and administer prophylactic treatment. • Appropriate pain relief management to reduce the stress of surgery • Neuraxial blockade. General anesthesia can result in a greater release of stress hormones compared to local or epidural anesthesia. Volatile anesthetic agents can inhibit insulin release and increase hepatic glucose output.

DIAGNOSIS • Preoperative blood sugar testing in all diabetics. • Intraoperative blood sugar testing should be considered in brittle diabetics and critically ill patients. • Postoperative blood sugar testing is typically performed in all diabetics in the recovery room. Cases that are short in duration, ambulatory, minimal stress, and/or performed with sedation may not require repeat testing in the recovery room (e.g., cataract, skin biopsies, etc).

DIFFERENTIAL DIAGNOSIS Inaccurate monitor results

TREATMENT • A multidisciplinary approach involving the anesthesia provider, surgeon, endocrinologist, intensivist, cardiologist, and dietitian may be necessary to minimize the perioperative morbidity and mortality in diabetic patients. • Preoperatively, blood glucose should be adequately controlled as per American Diabetes Association (ADA) recommendations. • HbA1C should ideally be <7% • Preprandial glucose between 90 and 130 mg/dL • Postprandial glucose <180 mg/dL • Schedule elective cases for diabetic patients early in the day. • On the day before surgery • Oral hypoglycemic drugs should be dosed normally • Long or intermediate acting insulin can be given in usual doses while taking a normal diet. Evening or night doses are normally decreased to avoid hypoglycemia on the day of surgery. • While NPO, order blood sugar checks frequently. If hypoglycemic, treat with 15–20 gm of glucose. Options include clear liquids, in the form of sugary drinks and fruit juices, sodas, or electrolyte solutions. • On the morning of the surgery • Hold oral hypoglycemic agents to prevent reactive hypoglycemia • Withhold short-acting insulin, but insulin pumps can be maintained at basal rate

• Intermediate insulin may be given according to the following formula: Fraction = [(Dosing interval in hours) – (Hours of fast during interval)]/Dosing interval in hours. For example, a patient is scheduled for hernioplasty. He will be eating normally at 10 am after minimally invasive anesthesia. – If he takes 24 U NPH daily at 7 am, then the fraction of intermediate insulin to give is (24 – 3)/24 = 7/8. Thus, at 7 am, he will receive 7/8th of his morning dose or 21 U of NPH. – If he takes 24 U of NPH twice a day at 7 am and 7 pm, then the fraction of insulin to give is (12 – 3)/12 = 3/4. Thus, at 7 am, he will receive 3/4th of his morning dose or 18 U of NPH. • For cases later in the day • Maintain a basal rate for patients on insulin pump • Consider advising that the patient takes a fraction of the intermediate acting insulin according to the formula above. • Consider allowing a small/light early snack such as toast (center-dependent). • Intraoperatively • Insulin-dependent diabetics: Consider administering an insulin infusion starting at 0.02 U/kg/h (100 U of insulin is mixed with 100 mL of IV fluid to yield a concentration of 1 U/mL) with a separate D5% or D5NS drip at 100–125 mL/h, for adult patients. Subsequent titration should be based upon the desired glucose target. • Alternatively, for insulin-dependent diabetics undergoing short procedures or minor surgeries, or noninsulin-dependent diabetics, scheduled glucose testing may be performed and treated as needed. • Correction of hyperglycemia may be performed with correction doses of ultra short-acting insulin; 1–4 U IV typically decreases blood sugar by 50 mg/dL. • Recovery room or on the inpatient ward. While the patient is NPO, sliding scale insulin dosing is commonly performed. When oral intake has resumed, oral medications may be restarted alongside a sliding scale regimen. In insulin dependent diabetics, regular insulin dosing may be restarted alongside a sliding scale regimen. • In the ICU • Some studies have documented decreased morbidity and mortality with normalization of blood glucose within a range of 140–150 mg/dL. • Type 1 diabetic patients require basal amounts of insulin. • Type 2 diabetic patients: Withhold all oral hypoglycemia agents to prevent reactive hypoglycemia. Patients with renal disease are at increased risk of lactic acidosis if treated with biguanides. • Initiate a sliding scale insulin infusion with a basal longer acting preparation to provide more consistent glucose control. • Subcutaneous insulin administration during critical illness may be unpredictable. • Transition from the intensive care to general care with basal-bolus insulin has been shown to demonstrate superior glycemic control. Ideally, the transition should take place either before leaving the ICU or shortly thereafter. Several techniques have been described and are often institution or practitioner specific. • The starting dose for subcutaneous insulin should be 50–80% of the total IV insulin dose over the last 24 hours; it may be given daily or divided into twice daily dosing as a long-

acting insulin analog (insulin detemir or insulin glargine). For example, if 72 U of IV insulin have been administered over 24 hours, then the subcutaneous insulin dosing would range from 36 to 58 U (QD or BID). – Alternatively, the Miami 4/12 formula can be utilized. Dosage of basal insulin = body weight (kg)/4. For example, a patient who weighs 72 kg needs 72/4 = 18 U of basal insulin. Dosage of bolus insulin = body weight (kg)/12. For example, a patient who weighs 72 kg needs 72/4 = 6 U of rapid-acting insulin before a meal. – The first dose of long-acting insulin should be given 2–3 hours and the short-acting insulin 1–2 hours before stopping an insulin infusion.

FOLLOW-UP • Patients, who were diagnosed as stress-induced hyperglycemia, requiring intensive insulin therapy or not known to be diabetic before, need outpatient follow-up to confirm the diagnosis of DM in an unstressed state. • Long-standing and uncontrolled diabetes can cause a myriad of intraoperative events: • Difficult intubation due to joint rigidity seen in Type 1 DM. • Risk of aspiration due to gastroparesis • Wide hemodynamic disturbances during induction

REFERENCES

1. Cowie CC,Rust KF, FordES, et al. Full accounting of diabetes and pre-diabetes in the U.S. population in1988–1994 and 2005–2006. 2. Diabetes Care.2009;32(2):287–294. 3. Fahy BG, Sheehy AM, Coursin DB. Glucose control in the intensive care unit. Crit Care Med. 2009;37(5):1769–1776. 4. Lipshutz AK, Gropper MA. Perioperative glycemic control: An evidence-based review. Anesthesiology. 2009;110(2):408–421. 5. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2005;28(Suppl 1):S37–42. 6. Marik PE. Glycemic control in critically ill patients: What to do post NICE-SUGAR? World J Gastrointest Surg. 2009;1(1):3–5. 7. Raju TA, Torjman MC, Goldberg ME. Perioperative blood glucose monitoring in the general surgical population. J Diabetes Sci Technol. 2009;3(6):1282–1287. 8. Vann MA. Perioperative management of ambulatory surgical patients with diabetes mellitus. Curr Opin Anaesthesiol. 2009;22(6):718–724.

ADDITIONAL READING

• Joshi GP, Chung F, Vann MA, et al.; Society for Ambulatory Anesthesia. Society for Ambulatory Anesthesia consensus statement on perioperative blood glucose management in diabetic patients undergoing ambulatory surgery. Anesth Analg. 2010;111(6):1378–1387.

• Meneghini LF. Perioperative management of diabetes: Translating evidence into practice. Cleve Clin J Med. 2009;76(Suppl 4):S53–59. • NICE-SUGAR Study Investigators; Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283– 1297.

See Also (Topic, Algorithm, Electronic Media Element) • Hypoglycemia • Diabetes mellitus

CODES ICD9

790.29 Other abnormal glucose ICD10 R73.9 Hyperglycemia, unspecified

CLINICAL PEARLS

• Postoperative hyperglycemia is associated with increased risk of infection, longer hospital stay, and myocardial infarction. • Hyperglycemia is a common complication in patients receiving enteral and parenteral nutrition. • Hypoglycemia is a barrier for the achievement of euglycemia in patients with diabetes.

HYPERKALEMIA

Michael S. Green, DO Poovendran Saththasivam, MD

BASICS DESCRIPTION

• Hyperkalemia is defined as a serum potassium >5.5 mEq/L. If it goes unrecognized or there is a delay in treatment, it can lead to cardiac and respiratory arrest. • Potassium is predominantly an intracellular cation and is important in electrophysiological functions. The body has several regulatory mechanisms to maintain the potassium concentration within narrow levels; to avoid hyperkalemia, the cation is shifted intracellularly and/or excretion is enhanced. • Hyperkalemia may present preoperatively or develop intraoperatively. The anesthesia provider must be vigilant in the identification and treatment of this potentially lifethreatening electrolyte abnormality. EPIDEMIOLOGY Incidence

Hospitalized patients: 1.1–10% Prevalence

• End-stage renal disease: 5–10% • Male:female ratio of 1:1

Morbidity

Increased in elderly patients with diabetes, chronic renal disease, and hypertension. Mortality

Untreated cases: 67%

ETIOLOGY/RISK FACTORS

• Altered internal balance: Acidosis, insulin deficiency, renal failure, decreased aldosterone levels, increased tissue breakdown. • Altered external balance: Blood transfusions, drugs that affect renal excretion or internal balance. • Pseudohyperkalemia: Thrombocytosis, leucocytosis, hemolyzed sample, increased release from abnormal cells. PHYSIOLOGY/PATHOPHYSIOLOGY

• Nearly 98% of total body potassium is intracellular; the remaining 2% is extracellular. The total potassium load in the body is ~50 mEq/kg (average 70 kg human has ~3500 mEq).

Serum potassium is usually maintained from 3.5 to 5.0 mEq/L. • Na+/K+ ATPase is located in the cell membrane. It is a counter-exchange mechanism that pumps Na+ extracellularly and K+ intracellularly in a 3:2 ratio. The pump functions to maintain the resting cell membrane potential, cell volume, and intracellular calcium concentration. It is further regulated by insulin, acidosis, drugs, and catecholamines. • Hyperkalemia from intracellular to extracellular shifting: – Insulin directly stimulates the Na+/K+ ATPase pump in the liver, skeletal muscle, and fat cells. It promotes intracellular uptake of potassium. Insulin deficiency can hence impair the transcellular uptake of glucose as well as the Na+/K+ ATPase pump. – Excessive tissue breakdown or increased cellular catabolism can result in a release of excessive amounts of potassium to the extracellular environment. Examples include malignant hyperthermia, rhabdomyolysis, massive hemolysis, and tumor lysis syndrome. – Beta-2 adrenergic agonists promote intracellular uptake of potassium by stimulating the Na+/K+ ATPase pump. Conversely, non-selective beta-blockers may decrease uptake. – Metabolic acidosis promotes potassium efflux via hydrogen ion exchange. For every 0.1 mmol/L decrease in pH, there is a 0.6 mmol/L increase in serum potassium. The Na+ H+ ion exchanger allows for the cells to function as a buffer against alkalemia or acidemia. In acidemia, H+ ions move intracellularly, in exchange for Na+ moving extracellularly. This reduces intracellular shifting of K+ via the Na+ - K+–ATPase. The opposite occurs in alkalemic states. – Hypertonicity leads to a loss of intracellular water and concentrates the intracellular potassium concentration. This creates a driving force that favors potassium movement out of the cell. – Medications, including NSAIDS and digoxin, impair the movement of potassium into the cell by inhibiting the Na+/K+ ATPase pump in the cell membrane. – Succinylcholine causes rapid transient hyperkalemia from “cellular leak.” • Hyperkalemia from impaired excretion occurs primarily from renal and gastrointestinal derangements. In the kidneys, excretion occurs mainly at the cortical collecting duct and aldosterone is a hormonal regulator of serum K+. Approximately 60–75% of filtered potassium in the glomerulus is reabsorbed in the proximal tubule and 15–20% in the thick ascending limb of the loop of Henle. Hyperkalemia stimulates aldosterone production with resultant renal tubular elimination of K+ and reabsorption of Na+ and water. – In patients with a glomerular filtration rate (GFR) of 5–10 mL/min, potassium excretion is impaired at the distal collecting duct as a result of a decrease in sodium and water delivery. Conditions like severe heart failure, dehydration, or hypovolemia also limit the sodium and water delivery to the distal collecting ducts. – Mineralocorticoid deficiency (aldosterone) can decrease excretion at the cortical collecting duct. – Medications such as potassium sparing diuretics (amiloride, triamterene) and antibiotics (trimethoprim-sulfamethoxazole, pentamidine) can decrease urinary potassium excretion by inhibiting the sodium channels in the kidney. – Aging results in decreased renal mass, renal blood flow, GFR, and loss of tubular transport function. This predisposes elderly patients to hyperkalemia. Additionally, elderly patients

are more likely to take NSAIDS, ACE inhibitors, beta-blockers, digitalis, and potassium sparring diuretics. • Hyperkalemia from increased intake – In patients with intact renal function, a supranormal intake is needed to cause hyperkalemia. In patients with impaired renal function (GFR <15 mL/min/1.73 m2), only a slight increase in potassium intake can cause severe hyperkalemia. • Electrophysiologic effects of hyperkalemia in heart muscles: – Hyperkalemia leads to an increased resting membrane potential (less negative; e.g., –90 mV to –80 mV) secondary to a decrease in the transmembrane potassium gradient. This result manifests as a shortening in the duration of the action potential in all cardiac cells. – Phase 0. When the membrane is partially depolarized, there are fewer sodium channels in the resting state that are ready for opening and ion conductance. This results in a decrease in the Vmax (phase 0), slowing of the impulse conduction, and prolongation of membrane depolarization. On the EKG, this is manifested by a prolonged P wave, PR interval, and QRS complex. – Phase 2 and 3. The potassium current in the myocyte membrane is responsible for the potassium efflux during these phases. Potassium currents increase during hyperkalemic states, via unknown mechanisms, leading to acceleration of repolarization. On the EKG, this is manifested by a peaked T wave. – Atrial tissue is more sensitive to hyperkalemia than the ventricles and nodal cells. At a potassium level of 8–9 mEq/L, the SA node may stimulate the ventricle without evidence of atrial activity, producing a sinoventricular rhythm. On the EKG, this is manifested as an absent P wave with a wide QRS complex. – As hyperkalemia worsens, SA node conduction ceases, and the passive junctional pacemaker becomes the primary electrical stimulation for myocardium. On the EKG, this is manifested as a QRS complex that continues to widen, blends with the T wave, and produces the classic sine wave pattern. At this point, ventricular fibrillation and asystole is imminent. • Pseudohyperkalemia is defined as a [K+] increase of at least 0.5 mEq/L and results from difficult phlebotomy, excessive alcohol swabbing of the skin, or clenching of the fist. When the value is excessive or does not fit the clinical picture, the lab draw should be repeated to confirm true hyperkalemia. PREVENTATIVE MEASURES

• Additional care and strict monitoring of serum potassium is needed for patients with impaired renal function or heart failure who are on spironolactone and ACE inhibitor. • Serial measurement of serum potassium coupled with EKG monitoring and management of the patient’s overall clinical condition can prevent fatal cardiac arrhythmia. • In patients with normal renal function, temporarily shifting potassium intracellularly can be therapeutic. In patients with poor renal function, shifting potassium intracellularly may need to be combined with hemodialysis.

DIAGNOSIS

• Plasma concentration >5.5 mEq/L – Mild hyperkalemia: 5.5–6.5 mEq/L – Moderate hyperkalemia: 6.5–7.5 mEq/L – Severe hyperkalemia: >7.5 mEq/L • Symptoms: Often asymptomatic thus, a clinical history of kidney disease or certain medications, coupled with laboratory and EKG results, aid in the diagnosis of hyperkalemia. • EKG changes are progressive and depend on the speed at which hyperkalemia manifests or changes. Progressive EKG manifestation are – Peaked T waves (5.5–6.5 mEq/L) – ST segment depression – Widening of the PR interval (>6.5 mEq/L) – Widening of the QRS interval – Loss of P wave (>8.0 mEq/L) – Sine wave pattern – Ventricular fibrillation – Asystole

DIFFERENTIAL DIAGNOSIS Pseudohyperkalemia

TREATMENT • Membrane stabilization with calcium in severe hyperkalemia or EKG manifestations (immediate) – IV calcium gluconate 10%: Infuse 10 mL over 10 minutes while monitoring the EKG. If no improvement, or EKG deterioration after initial improvement, repeat the dosage. Onset of action: <3 minutes. Duration of action: 30–60 minutes. – IV calcium chloride 10%: Provides three times more calcium. Infuse 3–10 mL over 10 minutes. Can cause tissue necrosis if extravasation occurs. • Redistribution of potassium into cells (quick) – Regular insulin 10 units IV with 50 mL of dextrose 50% is concomitantly given to prevent hypoglycemia. Onset of action is within 10–20 minutes and the peak effect is seen at 30– 60 minutes and persists for 4–6 hours. – IV or nebulized albuterol may be used as adjunctive therapy in severe hyperkalemia. Stimulates the Na+/K+ ATPase through beta-2 receptor agonism. The recommended dose is 0.5 mg IV or 20 mg nebulized. – Epinephrine 0.05 μg/kg/minute IV infusion, similarly, stimulates the Na+/K+ ATPase through beta-2 receptor agonism. – Sodium bicarbonate functions by increasing plasma pH and producing metabolic alkalosis. It is usually reserved for cases with severe acidosis, or if other indications for bicarbonate therapy are present. NaHCO3 is less effective for patients with renal failure. – Hyperventilation will transiently move K+ into cells by causing a temporary alkalosis. • Elimination of potassium from the body – Diuretics may be used for patients who are not volume depleted or do not have severe

renal impairment. Loop diuretics alone, or in combination with thiazide diuretics, may promote potassium excretion by enhancing distal sodium and water delivery to the principal cells in the cortical collecting ducts. – Hemodialysis is the most effective mechanism to eliminate potassium from the body.

REFERENCES

1. Lehnhardt A,Kemper MJ. Pathogenesis, diagnosis and management ofhyperkalemia. Pediatr Nephrol. 2010;25(3):403–413.

2. Palmer BF. A physiologic-based approach to the evaluation of a patient with hypokalemia. Am J Kidney Dis. 2010;56(6):1184–1190. 3. Weisberg LS. Management of severe hyperkalemia. Crit Care Med. 2008;36(12):3246– 3251. 4. Einhorn LM, Zhan M, Hsu VD, et al. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med. 2009;169(12):1156–1162. 5. Naderi AS, Palmer BF. An unusual case of acute hyperkalemia during pregnancy. Am J Obstet Gynecol. 2007;197(3):e7–8. 6. Parham WA, Mehdirad AA, Biermann KM, et al. Hyperkalemia revisited. Tex Heart Inst J. 2006;33(1):40–47.

ADDITIONAL READING

• Prough DS, Funston JS, Svensen CH, et al. Fluids, electrolytes, and acid-base physiology. In Barash PG et al. (Eds.), Clinical Anesthesia, 6th edn. Philadelphia: Lippincott Williams & Wilkins, 2009, p. 311.

See Also (Topic, Algorithm, Electronic Media Element) • Hypokalemia • Acid-base physiology • Diabetic ketoacidosis

CODES ICD9 276.7 Hyperpotassemia ICD10 E87.5 Hyperkalemia

CLINICAL PEARLS

• Exclude pseudohyperkalemia by repeating serum potassium in patients with normal EKG and no obvious risk factor for hyperkalemia. • Hyperkalemia is seen in diabetic ketoacidosis; it is caused by insulin deficiency that impairs

normal intracellular potassium movement. • Calcium gluconate protects the myocardium from fatal arrhythmia by reducing (more negative) the threshold potential of myocytes thus restoring the resting membrane potential. • Succinylcholine can cause elevation of serum potassium by 0.5–1 mEq/L with standard dosing.

HYPERNATREMIA

Michael S. Green, DO Poovendran Saththasivam, MD

BASICS DESCRIPTION • Hypernatremia is defined as a serum [Na+] >145 mEq/L; it indicates an absolute or relative water deficit. • Major causes include – Excessive loss of water – Inadequate water intake – Lack of antidiuretic hormone (ADH) – Excessive sodium intake from iatrogenic causes or accidental administration • Hypernatremia results in a hypertonic, hyperosmolar state within the extravascular compartment that draws water from the intracellular compartment causing cell shrinkage. This concept is harnessed therapeutically in patients with intracranial hypertension to decrease intracranial volume. EPIDEMIOLOGY Incidence

Found in ∼1% of hospitalized patients. Prevalence

• Increased in patients who are intubated, have altered mental status, and where access to water is compromised (e.g., infants and elderly). In infants, it is usually associated with diarrhea or severe febrile illness. • Diagnosed equally among males and females.

Morbidity

• Severe hypernatremia, defined by a [Na+] >160 mEq/L, or rapid onset of less than 12 hours, can result in intracranial bleeding, convulsions, neurologic deficits, and coma. • Chronic hyperosmolality and hypotonic fluid treatments can also cause cerebral edema, convulsions, coma, and death.

Mortality

Varies widely and is dependent on the severity of the condition and the rapidity of onset. • Acute changes: 42–75% • Chronic changes: 10–60% ETIOLOGY/RISK FACTORS

• Inadequate water intake (no gain in sodium)

– Restricted access to water; seen in nursing home or hospitalized persons who are dependent on others to meet fluid requirements. – Impaired thirst mechanisms can result from a defect in the osmoreceptor or cortical thirst center as well as structural lesions involving the hypothalamus. • Hypotonic fluid loss – Diabetic insipidus: Both central and nephrogenic causes – Gastrointestinal (GI) losses: Diarrhea, vomiting, fistula – Burns – Peritoneal dialysis – Insensible losses: Skin (excessive sweating), respiratory tract – Renal losses: Osmotic diuresis as a result of hyperglycemia or diuretic therapy (mannitol), postobstructive diuresis • Sodium overload (in excess of body water) – Excessive sodium intake: Iatrogenic causes include IV sodium bicarbonate or hypertonic saline (3% normal saline contains 30 g/L of sodium chloride which is equivalent to a [Na+] of 513 mEq/L); excessive PO salt intake. – Mineralocorticoid excess: Cushing’s syndrome, hyperaldosteronism • Medications that affect the function of the renal collection system: Lithium, glyburide, foscarnet, demeclocycline, amphotericin B, methoxyflurane.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Under normal conditions, the sodium concentration is tightly regulated and maintained within a narrow range. Increases in sodium stimulate a strong thirst sensation and ADH release from the pituitary gland to re-establish normal levels. Physiological values are crucial to a myriad of functions within the human body: – Maintains normal electrophysiological balance of the cell membrane. The normal transmembrane potential is maintained by the Na+/K+-ATPase pump, which pumps 3 sodium ions out of the cell for every 2 potassium ions transported into the cell. – Maintains water homeostasis (water follows sodium) – Maintains normal extracellular and intracellular osmolality – Conducts electrical impulses in nerves, muscle, and cardiac tissue via specialized sodium channels. – Regulates blood pressure BP via aldosterone’s effects • General effects of hypernatremia: Hypertonic hyperosmolality that causes movement of water from the intracellular to extracellular space and results in intracellular compartment shrinkage. • Hypernatremia and the central nervous system: To offset cellular shrinkage, the brain increases intracellular solute uptake. Adverse effects include – Intracranial bleeding. The brain is pulled away from the calvarium and can cause tearing of the bridging veins. Intraparenchymal bleeding results from capillary enlargement and rupture from cell shrinkage. – Encephalopathy. Cellular shrinkage disrupts synaptic transmission and brain cell function. • Hypernatremia and the cardiovascular system. Rapid increases in serum sodium result in volume overload (fluid shifting out of the intracellular space) and can overwhelm the left

ventricle with resultant dysfunction. Fluid may “backup” into the pulmonary vasculature and result in cardiogenic pulmonary edema. Conversely, the administration of hypertonic saline has been used to treat severe hypovolemia (e.g., trauma) by drawing water into the vasculature/circulation. • Hypernatremia and the renal system. Studies in rats have shown that an acute increase in serum sodium leads to renal vasodilatation. Hypertonic saline infusions stimulate vasopressin and oxytocin, alter sympathetic activity, cause transient hypertension, and result in a sustained increase in renal blood flow. • Central diabetes insipidus (DI) describes impaired ADH synthesis that manifests as polyuria and defects in the ability to concentrate urine. The kidneys cannot produce/maintain the hypertonic medullary interstitium that is required to concentrate urine; this results in a solute (osmotic) diuresis and excessive free water loss. Central DI may be seen after pituitary surgery, severe head trauma (damage to the neurohypophyseal stalk), or basilar skull fracture. • Nephrogenic diabetic insipidus describes renal resistance to ADH; it manifests similarly to central DI (polyuria and an inability to concentrate urine). Hereditary nephrogenic DI can result from a gene mutation of the ADH receptor or the AQP-2 water channel. Acquired nephrogenic DI is commonly due to lithium toxicity or metabolic abnormalities, particularly hypokalemia and hypercalcemia. • Mineralocorticoid excesses will increase aldosterone levels, leading to potassium depletion and sodium retention (increase in total body sodium). Aldosterone acts on the distal collecting ducts to increase tubular reabsorption of sodium and potassium excretion.

PREVENTATIVE MEASURES

Free water loss via the GI, respiratory, and urinary tract should be replaced in critically ill patients.

DIAGNOSIS Pediatric Considerations

Symptoms include hyperpnea, muscle weakness, restlessness, a characteristic high pitched cry, insomnia, lethargy, and coma. Signs and symptoms • Lethargy, mental status changes, irritability • Thirst, shock, peripheral edema, ascites, and myoclonus • Muscular tremor, rigidity, hyperactive reflexes, and spasticity • Serum [Na+] >145 mEq/L • If the urine output is >100 mL/hour with hypernatremia, the patient should be evaluated for DI. A urine osmolality <300 mOsm/L and serum sodium >150 mEq/L makes the diagnosis of DI likely.

DIFFERENTIAL DIAGNOSIS

Must make a distinction between the three types: • Low total body sodium (loss of water >sodium); also referred to as hypovolemic

hypernatremia – Renal: Osmotic diuresis from hyperglycemia or mannitol. Urine [Na+] >20 mOsm/L – Extrarenal: Diarrhea, insensible fluid losses, vomiting. Urine [Na+] <10–20 mOsm/L • Normal total body sodium (water loss); also referred to as euvolemic hypernatremia – Renal: Central and renal DI. Urine osmolality: Low. Urine [Na+]: Variable. – Extrarenal: Impaired water intake. Urine osmolality: High Urine [Na+] >20 mOsm/L. • High total body sodium (gain of sodium >water) and includes hypertonic saline; also referred to as hypervolemic hypernatremia. Urine [Na+] >20 mOsm/L

TREATMENT • Depends on the underlying cause and course of development – In chronic hypernatremia, brain cells accumulate organic osmoles when intracellular water is lost, thus minimizing cell shrinkage. If corrected too fast, cerebral edema will occur as a result of rapid uptake of water into brain cells that outpaces the extrusion of organic osmoles and electrolytes from the brain cells. To that extent, a reduction in serum [Na+] by <10 mEq/day, or 0.5 mEq/hour in chronic hypernatremia, is recommended. – In acute hypernatremia, rapid correction (e.g., 1 mEq/hour) may not increase the risk of cerebral edema. • High total body sodium/hypervolemic hypernatremia. Excessive salt and water can be corrected with a potent diuretic (e.g., furosemide) combined with a hypotonic solution such as D5%W. Alternatively, hemodialysis may be utilized. • Normal total body sodium/euvolemic hypernatremia. – Central DI. Intranasal DDAVP 5–10 μg once or twice daily or aqueous vasopressin SC 5–10 U twice daily. In an emergency, IV DDAVP 1–2 μm BID or TID. – Nephrogenic DI. Thiazide diuretics with or without prostaglandin synthetase inhibitors (e.g., indomethacin or amiloride) and modest sodium restriction. • Low total body sodium/hypovolemic hyponatremia. Correct hypovolemia using 0.9% normal saline followed by correction of the water deficit with a hypotonic solution. The free water deficit can be estimated as follows: Total body water (TBW) × [(serum Na+/140) – 1]. The TBW for males and females are 0.6 and 0.5 multiplied by the lean body weight, respectively. In elderly patients and those with significant dehydration, a more conservative estimate is needed (0.5 for males and 0.4 for females). – For example, a male patient with a body weight of 70 kg presenting with a serum sodium of 160 mEq/L would have a free water deficit = 70 × 0.6 × [(160/140) – 1]; this is equal to 42 × 0.143 or 6 L. – Correction of the water deficit can occur with oral intake, a G tube, or IV replacement using D5%W or 0.45% NaCl.

REFERENCES

1. Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342(20):1493–1499. 2. Wakil A, Atkin SL. Serum sodium disorders: Safe management. Clin Med. 2010;10(1):79–

82. 3. Prough DS. Physiologic acid-base and electrolyte changes in acute and chronic renal failure patients. Anesthesiol Clin North America. 2000;18(4):809–833.

4. Robertson G, Carrihill M, Hatherill M, et al. Relationship between fluid management, changes in serum sodium and outcome in hypernatraemia associated with gastroenteritis. J Paediatr Child Health. 2007;43(4):291–296. 5. Leung C, Chang WC, Yeh SJ. Hypernatremic dehydration due to concentrated infant formula: Report of two cases. Pediatr Neonatol. 2009;50(2):70–73.

ADDITIONAL READING

• Prough DS, Funston JS, Svensen CH, et al. Fluids, electrolytes, and acid-base physiology. In Barash PG et al. (Eds.), Clinical Anesthesia, 6th edn. Philadelphia: Lippincott Williams & Wilkins, 2009, p. 309.

See Also (Topic, Algorithm, Electronic Media Element) • Diabetes insipidus • Cushing’s syndrome • Crystalloids

CODES ICD9 276.0 Hyperosmolality and/or hypernatremia ICD10 E87.0 Hyperosmolality and hypernatremia

CLINICAL PEARLS

• Hypernatremia increases the minimum alveolar concentration of inhaled anesthetic agents, possibly because of enhanced sodium conductance during depolarization of excitatory membranes. • Common errors in the correction include underestimation of fluid deficit, ongoing fluid losses, and maintenance fluid requirement.

HYPEROSMOLAR HYPERGLYCEMIC NONKETOTIC (HHNK) COMA Jeffrey Katz, MD Ori Gottlieb, MD

BASICS DESCRIPTION

• Hyperosmolar hyperglycemic nonketotic (HHNK) coma is defined as a – Severe hyperglycemic state (often >600 mg/dL) – Hyperosmolarity (often >320 mOsm/kg) – Hypovolemia from glycosuria – Central nervous system (CNS) depression • It is more commonly seen in older patients with noninsulin-dependent diabetes. • HHNK is differentiated from diabetic ketoacidosis (DKA) in that the magnitude of acidosis and ketosis are less profound and often develop more insidiously. However, it should be noted that up to one-half of patients with diabetic ketoacidosis also have hyperglycemic hyperosmolarity. EPIDEMIOLOGY Incidence

• Lower incidence than DKA • HHNK accounts for <1% of all primary admissions for diabetes mellitus (DM) • Exact incidence is unknown due to a lack of population studies.

Prevalence

• Mean age of onset in the 7th decade • Increased in elderly and institutionalized patients

Morbidity

Typically from the precipitating disease. Mortality

Ranges from 10 to 20%; death is typically related to the precipitating cause. ETIOLOGY/RISK FACTORS

• Noninsulin-dependent DM (baseline decreased insulin levels) • Increased glucose levels – Poor diabetes medication compliance – Corticosteroids – Sympathomimetics – Cardiopulmonary bypass

– Hyperalimentation or total parenteral nutrition • Altered thirst response or compromised access to free water – Advanced age – Institutionalized patients – Sepsis – Infections (urinary tract infections, pneumonia, sepsis) – Diuretics

PATHOPHYSIOLOGY

• In noninsulin-dependent diabetics, increased blood glucose levels are further exacerbated by decreased fluid intake, increased fluid loss, or impaired renal function. The kidneys excrete glucose in the urine; however, this ability can become impaired in the setting of hypovolemia causing a decrease in the glomerular filtration rate or renal dysfunction. Of note, hypovolemia is further compounded by the osmotic diuresis that ensues as a result of hyperglycemia. • Gluconeogenesis. The body mounts a stress response to the inciting event with counterregulatory hormones (glucagon, cortisol, growth hormone). The liver is stimulated to increase glucose production and decrease utilization, further exacerbating hyperglycemia. This occurs to a lesser extent than in DKA. • Electrolytes. Total body deficits of potassium, sodium, chloride, phosphate, calcium, and magnesium result. – Potassium. Similar to DKA, patients may initially present with hyperkalemia due to extracellular shifting of the ion, but are total body depleted. This is due to several causes: Metabolic acidosis: H+ ions moves intracellularly via the Na+–H+ ion exchanger while Na+ moves extracellularly. This reduces intracellular shifting of K+ via the Na+/K+ ATPase. Decreased insulin levels: Decreases the Na+/K+ ATPase pump activity that moves potassium intracellularly. Osmotic diuresis: Potassium is excreted in the urine Catabolism: Chronic states result in total body depletion – Sodium. Depletion occurs due to osmotic diuresis. However because water losses may exceed sodium losses, a hypovolemic hypernatremic state may be initially present.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Delay elective procedures. The goal is to re-establish euvolemia and electrolyte levels as much as possible before going to the operating room. • Indication for emergency surgery may be the precipitating illness for HHNK coma and thus full preoperative correction is not always possible. In this case, initiate measures to restore euvolemia and replete electrolytes as the first priority, then correct hypoglycemia.

PREOPERATIVE ASSESSMENT SYMPTOMS

Mental status changes

History

• Evaluate diabetes severity, prior episodes of HHNK coma, and comorbidities • Determine the underlying/inciting cause • Time of onset

Signs/Physical Exam

• Volume status • Neurologic assessment • Shock • Polyuria • Vomiting

TREATMENT HISTORY

• Volume resuscitation • Potassium management (hyperkalemia versus hypokalemia); recall that total body stores are decreased, but that extracellular shifting of potassium may lead to dangerously elevated serum levels. • Intubation for airway protection if the patient has altered mental status

MEDICATIONS

• Insulin administration • Antibiotics if precipitating event is sepsis or infection

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Serum glucose • HbgA1C (to evaluate glucose control over the past 3 months) • Electrolytes (potassium, sodium) • BUN/Cr • Arterial blood gas • Urine and serum ketones • EKG may demonstrate abnormalities related to hyperkalemia or hypokalemia

CONCOMITANT ORGAN DYSFUNCTION

• Neuropathy – Autonomic nervous system dysfunction may result in difficulties with regulating blood pressure and temperature. • Gastroparesis – Many consider patients with DM as a “full stomach” despite NPO status. • Cardiovascular disease – Macrovascular disease of the coronary arteries increases morbidity and mortality in diabetics. • Renal insufficiency results from microvascular disease of renal vessels. • Nonenzymatic glycosylation and formation of abnormal proteins may result in decreased elastance and thus difficult intubation. CIRCUMSTANCES TO DELAY/CONDITIONS

Delay elective procedures. In urgent or emergent procedures, reestablish euvolemia and

electrolyte levels as much as possible before going to the operating room. CLASSIFICATIONS

Hyperglycemic crisis of DM include HHNK and DKA. These disorders are differentiated by the magnitude of acidosis and lack of ketosis; however, they can overlap.

TREATMENT PREOPERATIVE PREPARATION Premedications

In emergent surgeries, treatment with volume resuscitation, insulin infusion, and electrolyte replacement should be continued en route to the operating room. Special Concerns for Informed Consent

• May not be possible to attain consent from the patient. • Family members should be advised about the severity of their condition, emergent nature of the surgery, and the increased risk of mortality. INTRAOPERATIVE CARE Choice of Anesthesia

General endotracheal anesthesia is almost always chosen; patients with mental status changes make poor candidates for sedation or regional blocks. Monitors

• Standard ASA monitors • Arterial line may be useful for frequent lab checks as well as to monitor beat-to-beat BP in patients that are hypovolemic. • Foley catheter. Ins and outs should be carefully monitored • Some consider CVP monitoring to be useful in guiding fluid administration.

Induction/Airway Management

• Endotracheal tube for airway protection is most often utilized. • Patients are hypovolemic and may become unstable with induction medications. Consider etomidate and/or ketamine, if appropriate. The risks of adrenocortical suppression with the use of etomidate need to be considered, however. • Induction agents may have effects on glucose homeostasis but are likely clinically insignificant. Maintenance

• Intensive care therapy should be continued in the operating room in the same manner. • Labs – Blood glucose – Electrolytes • Volume resuscitation

– If severe hypovolemia, 0.9% normal saline (NS) resuscitation. – If mild hypovolemia, consider 0.45% NS if high/normal [Na+] and 0.9% NS if low [Na+]. • Insulin therapy – Regular insulin 0.1 units/kg initial IV bolus – Insulin infusion at 0.1 units/kg/hour • Potassium replacement – If the [K+] >5.3 mEq/L, continue insulin and monitor every 2 hours. – Be cautious in patients with impaired renal function • Normothermia. Hypothermia decreases the response to insulin.

Extubation/Emergence

Base the decision to extubate on mental status, volume status, and hemodynamic stability.

POSTOPERATIVE CARE BED ACUITY

ICU admission is commonly indicated for altered mental status, hypovolemia, shock requiring vasopressors, or if insulin infusions are still required. MEDICATIONS/LAB STUDIES/CONSULTS

• Endocrine consult may be advantageous • Frequent blood glucose checks • Electrolytes monitoring. Potassium moves intracellularly as the acidosis is corrected

COMPLICATIONS

• Inadequate resuscitation • Hypoglycemia may result from excess insulin therapy. • Overzealous potassium replacement can lead to cardiac arrhythmias. • Pulmonary edema/heart failure from overzealous fluid administration. • Cerebral edema or central pontine myelinosis from rapid correction of sodium imbalance.

REFERENCES

1. Hirsch I, et al. Perioperative management of surgical patients with diabetes mellitus. Anesthesiology. 1991;74:346–359. 2. Kitabchi A, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2006;29(12):2739–2748. 3. Milaskiewicz R, et al. Diabetes and anaesthesia: The past decade. Brit J of Anaesth. 1992;68:198–206. 4. Lorber D. Nonketotic hypertonicity in diabetes mellitus. Med Clin North Am. 1995;79(1):39–52. 5. Matz R. Management of the hyperosmolar hyperglycemic syndrome. Am Fam Physician. 1999;60(5):1468–1476. See Also (Topic, Algorithm, Electronic Media Element)

• Diabetic ketoacidosis • Diabetes mellitus • Hyperkalemia • Hypokalemia • Hypernatremia

CODES ICD9

250.20 Diabetes with hyperosmolarity, type II or unspecified type, not stated as uncontrolled ICD10

E11.01 Type 2 diabetes mellitus with hyperosmolarity with coma

CLINICAL PEARLS

• Pure HHNK differs from DKA in that the degree of hyperglycemia and dehydration is greater, whereas the degree of acidosis, lipolysis, and ketosis is absent or minimal. Additionally there is CNS depression. • The mortality of HHNK is greater than DKA. Mortality is associated with the underlying disease process, not hyperglycemia. • Delay elective surgery until the patient is adequately volume and electrolyte repleted.

HYPERTENSION

Gundappa Neelakanta, MD

BASICS DESCRIPTION

According to the Joint National Committee’s 2003 report, hypertension is defined as a systolic blood pressure (BP) >140 mm Hg or a diastolic BP >90 mm Hg. EPIDEMIOLOGY Incidence

• Affects ∼50 million people in the US (almost 25% of US adult population) and 1 billion people worldwide. • Individuals who are normotensive at age 55 years have a 90% lifetime risk of developing hypertension. Prevalence

Increases with age. About half of all adults between the ages of 60 and 69 years and three quarters of all adults age >70 years have hypertension. Morbidity

• A linear relationship exists between an increase in BP and risk of developing ischemic heart disease and stroke. • Randomized controlled trials have provided unequivocal proof that lowering BP with regular medication dramatically reduces cardiovascular disability and death, and slows the progression of chronic kidney disease • Patients with isolated systolic hypertension also have a higher cardiovascular morbidity. • There is increasing evidence that patients with labile and white coat hypertension are also at increased risk of cardiac and vascular complications. Mortality

Worldwide: ∼7.5 million deaths annually are attributable to hypertension. ETIOLOGY/RISK FACTORS

• Essential (primary) hypertension describes high BP when no cause has been identified. Associated factors include obesity, excess dietary sodium intake, reduced physical activity, inadequate intake of fruits, vegetables and potassium, and excess alcohol intake. • Secondary hypertension (<5%) is due to identifiable causes such as sleep apnea, druginduced or related causes, chronic kidney disease, primary aldosteronism, renovascular disease, chronic steroid therapy, Cushing’s syndrome, pheochromocytoma, coarctation of the aorta, thyroid, or parathyroid disease. PATHOPHYSIOLOGY

• The pathogenesis of essential hypertension is not completely understood. Studies have suggested that it may result from impaired sodium excretion by the kidneys, or an overactive renin-angiotensin or sympathetic nervous system. During the early stages, an increase in cardiac output and normal total peripheral resistance is seen. Over time, the cardiac output returns to normal levels, but the total peripheral resistance increases and intravascular volume decreases • The relative intravascular volume depletion can become unmasked with sympatholysis from anesthetic medications and neuraxial techniques.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Perioperative anesthetic management aims to maintain hypertensives within a range of 10– 20% of preoperative values. However, increased vascular stiffness and decreased vascular filling predispose patients to greater swings in BP. Thus, tight control may require the use of antihypertensives, vasopressors, and invasive monitoring. • There is conflicting evidence that mild-to-moderate preoperative hypertension in the absence of target organ damage is an independent predictor of postoperative cardiac complications of cardiac death, postoperative myocardial infarction (MI), heart failure, or arrhythmias. • Cardiac events in hypertensives occur at a higher frequency in the perioperative period for cardiac surgery, carotid artery surgery, peripheral vascular surgery, abdominal aortic surgery, and thoracoabdominal surgery. • Severe hypertension or crisis in the perioperative period (diastolic BP >120 mm Hg) or impending organ damage poses definite risks of cardiac complications such as myocardial ischemia, MI, or stroke. Causes may include abrupt withdrawal of clonidine or betablockers, interaction of monoamine oxidase inhibitors (MAO) with sympathomimetic agents, pheochromocytoma, preeclampsia, or eclampsia. • Preoperative BP medications should be continued in the preoperative as well as perioperative period. ACE inhibitors and ARBs may cause profound and refractory hypotension when taken on the morning of surgery; however there are no guidelines at this time on how to manage.

PREOPERATIVE ASSESSMENT SYMPTOMS

Usually asymptomatic History

• Preoperative increases in BP due to anxiety or white coat syndrome can be distinguished from previous clinic BP measurements. • A “silent killer.” ∼30% of adults are unaware of their hypertension and may present to the preoperative suite undiagnosed. • Questioning should be directed at determining the severity, presence of target organ damage, and associated comorbidities.

Signs/Physical Exam

• Vital signs, peripheral pulses, body mass index (BMI) • Cardiac examination • Auscultation for carotid, abdominal, or renal bruits and assessment for abdominal or renal masses. TREATMENT HISTORY

This may include adoption of healthy lifestyles that reduce, prevent or delay hypertension, and increase the efficacy of antihypertensive medications. Lifestyle modifications include adoption of dietary changes that are low in salt and rich in fruits and vegetables, limitation of alcohol intake, regular exercise, and weight loss. MEDICATIONS

• Drug type, recent changes, and compliance should be reviewed. Over 40% of patients with hypertension do not take medications and 2/3rd are not optimally controlled. Furthermore, most patients are on more than one antihypertensive. • Diuretics. Thiazide-type diuretics are first-line treatment for most patients with uncomplicated hypertension, either alone or in combination with other classes. • Beta-blockers • Calcium channel blockers • Alpha-adrenergic blockers • ACE inhibitors/angiotensin receptor blockers (ARBs) • Central sympatholytics • Direct vasodilators • Hypertensive patients with diabetes mellitus (DM), chronic kidney disease, heart failure, post-MI, high coronary disease risk, and recurrent stroke prevention are compelling indications for treatment with a certain, specific class of antihypertensives.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Renal function: CBC, electrolytes, BUN, creatinine, glucose, urinary albumin • Cardiovascular function: Chest radiography, EKG, stress test or coronary angiography, as appropriate • Cerebrovascular function: Carotid artery duplex scan, as appropriate

CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular, cerebrovascular, renovascular, and peripheral vascular disease • Obesity, sleep apnea, DM • Untreated hypertension can lead to target organ damage of the heart (LVH, angina, and heart failure), brain (stroke or transient ischemic attack, dementia), chronic kidney disease, peripheral arterial disease, and retinopathy.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Preoperative diastolic blood pressure (DBP) <110 mm Hg. Studies have suggested that patients can safely undergo elective surgery. • Hypertensive urgency describes a severe elevation in BP without progressive end-organ

dysfunction. Preoperative DBP >110 mm Hg have been associated with an increased risk of cardiac and vascular morbidity; thus elective surgery may be postponed until good antihypertensive control has been achieved. However, there is increasing evidence that in the absence of cardiac, vascular, or renal complications in this population, immediate control of hypertension prior to surgery may be effective in preventing complications. • Hypertensive emergencies describe a DBP >120 mm Hg AND accompanying end-organ dysfunction. Surgery should be delayed for emergent treatment.

CLASSIFICATIONS

• BP readings are the average of two or more seated checks on each of two or more separate office visits. • Prehypertension: Systolic blood pressure (SBP) 120–139 mm Hg, DBP 80–89 mm Hg • Stage 1: SBP 140–159 mm Hg, DBP 90–99 mm Hg • Stage 2: SBP >160 mm Hg, DBP >100 mm Hg. • Hypertensive urgency: Severe elevation without progressive end-organ dysfunction. • Hypertensive crisis/emergency: SBP >180 mm Hg, DBP >120 mm Hg and accompanying end-organ damage (hypertensive encephalopathy, intracerebral hemorrhage, subarachnoid hemorrhage, acute stroke, unstable angina, acute MI, congestive heart failure, acute renal dysfunction, and acute aortic dissection)

TREATMENT PREOPERATIVE PREPARATION Premedications

• In general, antihypertensive medications should be continued in the preoperative and postoperative period. An increased risk of intraoperative bradycardia has been associated with beta-blockers and intraoperative hypotension with calcium channel blockers, ACE inhibitors, and ARBs on the morning of surgery. • Anxiolytics such as midazolam are extremely useful to decrease the level of anxiety and consequent increases in BP prior to surgery. INTRAOPERATIVE CARE Choice of Anesthesia

• Dependent on the type and site of surgery, associated comorbidities, patient’s preference, etc. • Regional anesthesia may, however, obtund the sympathetic hypertensive response to surgical stimuli. Hypotension may occur with neuraxial blocks, especially in the presence of hypovolemia. Monitors

• Standard ASA monitors are adequate in most patients. • Invasive arterial line monitoring for continuous BP monitoring is indicated in patients with uncontrolled hypertension, certain comorbidities, or surgical procedures.

• Other invasive hemodynamic monitoring may be indicated based upon comorbidities, surgical procedure.

Induction/Airway Management

• Time of wide BP swings that can result in impaired myocardial oxygen supply or demand. Consider frequent cycling and anticipate and treat perturberances. • Choice of induction medication is less important than careful titration. Hypotension can result from sympatholytic and/or direct vasodilatory effects combined with intravascular volume depletion, and is commonly treated with a fast onset, short duration vasopressor. • Hypertensive stress responses to airway manipulation may be decreased with the prophylactic or therapeutic use of fentanyl, beta-blockers, or vasodilator drugs such as nitroglycerine.

Maintenance

• None of the modern inhalational anesthetic agents have been shown to have any advantages over the other. • Hypertension is usually the result of light anesthesia, surgical stimulus, drug errors, hypoxia, hypercarbia, or fluid overload. Unusual causes of sudden, unexpected, or severe hypertension in the perioperative period include undiagnosed pheochromocytoma, hyperthyroidism, malignant hyperthermia, intracranial hypertension, or other causes mentioned above related to withdrawal of drugs like clonidine or interaction of MAO inhibitors with sympathomimetic agents. • Hypotension should be carefully avoided to maintain cerebral blood flow (CBF) as there is likely a right shift in the cerebral autoregulation curve. Common causes of intraoperative hypotension include hypovolemia, anesthetic drug overdose, or interaction with betablockers, calcium channel blocker, ACE Inhibitors, or ARBs.

Extubation/Emergence

Anticipate a hypertensive response and be prepared to treat.

POSTOPERATIVE CARE BED ACUITY

Uncontrolled hypertension requires a higher level of care and monitoring. MEDICATIONS/LAB STUDIES/CONSULTS

Resume antihypertensive medications as soon as possible after surgery. If oral intake is not possible, the drug should be administered via the nasogastric tube or IV route (equivalent doses, preferably same class). COMPLICATIONS

• Hypertension may result from pain or a full bladder. Other causes include hypoxia, hypercarbia, fluid overload, drugs, and cerebrovascular accident. • Unexpected severe hypertension in the intraoperative or perioperative setting should lead to suspicion of undiagnosed pheochromocytoma.

REFERENCES

1. The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 Report. JAMA. 2003;21(289):2560–2572. 2. mith I, Jackson I. Beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors and angiotensin receptor blockers: Should they be stopped or not before ambulatory anaesthesia? Curr Opin Anesthesiol. 2010;23:687–690.

3. Fayad A, Yang H. Is peri-operative isolated systolic hypertension (ISH) a cardiac risk factor? Curr Cardiol Rev. 2008;4:22–33. • Mancia G. Blood pressure reduction and cardiovascular outcomes: Past, present, and future. Am J Cardiol. 2007;100:3J–9J.

See Also (Topic, Algorithm, Electronic Media Element) • Perioperative hypertension • Pregnancy-induced hypertension • Geriatric physiology • ACE inhibitors and hypotension

CODES ICD9 401.9 Unspecified essential hypertension ICD10 I10 Essential (primary) hypertension

CLINICAL PEARLS

• Uncontrolled and untreated hypertension increases cardiac, vascular, cerebrovascular morbidity and kidney disease progression. Chronic treatment and adequate control of hypertension reduces these complications. • Patients with hypertension are more prone to swings in BP perioperatively. • Isolated systolic hypertension is associated with higher incidence of cardiac complications and arrhythmia. • Preoperative hypertension. Ensure correct BP readings: Patient seated, feet down, arms at the heart level, cuff encircling at least 80% of arm’s width, and SBP measured at the beginning of Korotkoff sounds and DBP measured at the disappearance of Korotkoff sounds. • Chronic hypertension shifts the cerebral blood flow autoregulation curve to the right.

HYPERTHERMIA

Praveen Kalra, MBBS, MD, FCCP

BASICS DESCRIPTION

• Hyperthermia is defined as an elevation of core body temperature above the normal diurnal range of 36–37.5°C and is due to a failure of thermoregulation. • It is not synonymous with fever, which is regulated at the level of the hypothalamus in the setting of inflammation and cytokine release. Febrile patients are commonly encountered in the ICU setting and present perioperatively (for surgery or have postoperative fever). Postoperative fever includes the pneumonic: Wind (pulmonary causes such as aspiration, pulmonary embolism, pneumonia), water (UTI), wound (surgical site infections), walking (deep venous thrombosis), and “what did we do” (medications, blood product transfusions, intravascular, urethral, nasal, and abdominal catheters). Postoperative fever includes the pneumonic: – Wind: Pulmonary causes such as aspiration, pulmonary embolism, pneumonia – Water: Urinary tract infection – Wound: Surgical site infection – Walking: Deep venous thrombosis – “What did we do:" Medications, blood product transfusions; intravascular urethral, nasal, abdominal catheters • Hyperthermia has perioperative relevance ranging from passive hyperthermia (excessive heating, most common in infants and children) to drug reactions (malignant hyperthermia [MH] neuroleptic malignant syndrome [NMS]) to increased incidence in laboring patients who receive epidural anesthesia. EPIDEMIOLOGY Incidence

• NMS in patients taking neuroleptic drugs ranges from 0.02–3% • Unexplained postoperative fever: Incidence remains ill-defined; however, studies suggest that it is common and resolves within 48 hours without antibiotic treatment. Morbidity/Mortality

• Heat stroke mortality: 21–63% • MH: 1–17% (prior to introduction of dantrolene, as high as 70%) • NMS mortality: 10–20%.

ETIOLOGY/RISK FACTORS

• Iatrogenic perioperative causes – Conductive warming systems – Fluid and blood warmers

– Warm operating rooms • Drug reactions – Malignant hyperthermia: Succinylcholine, volatile inhalational agents – Neuroleptic drugs (NMS) – Atropine – Salicylates – Lithium – Sympathomimetics – Serotonergic syndrome • Fever (Wind, water, wound, walking, “what did we do") – Urinary tract infections – Abscesses – Catheter-related infections – Sepsis – Meningitis – Pneumonia – Atelectasis – Wound infections • Endocrine – Hyperthyroidism – Thyroid storm

PHYSIOLOGY/PATHOPHYSIOLOGY

• Body temperature is maintained within a narrow range and is a balance between heat production and heat dissipation. It is regulated by the thermoregulatory center located in the anterior hypothalamus and varies over the course of the day. – Heat production results from metabolic processes as well as heat absorption from the environment. – Heat loss is principally via evaporation to the environment (ineffective above a relative humidity of 75%). Other methods of heat dissipation include radiation (emission of infrared electromagnetic energy), conduction (direct transfer of heat to an adjacent cooler object), and convection (direct transfer of heat to convective air currents). However, these processes are inefficient when the environmental temperature exceeds skin temperature. • Temperature elevation causes increased oxygen consumption and metabolic rate with resultant tachypnea, hypercarbia, and tachycardia; as well as a reduced mixed venous oxygen saturation. Thus, increased oxygen demand can aggravate preexisting cardiac or pulmonary insufficiency. Above 37°C, each one degree increase corresponds to an ∼13% increase in oxygen consumption. Above 42°C (108°F), oxidative phosphorylation is uncoupled, making enzymes nonfunctional and thus putting the patients at risk for multiple organ failure. Hepatocytes, vascular endothelium, and neural tissues are most sensitive to these effects. • Hyperthermia does not involve resetting the thermoregulatory centers; it remains unchanged and can lead to uncontrolled increases in body temperature that can be rapidly fatal. • MH is a rare genetic disorder that is triggered by succinylcholine administration or exposure

to volatile inhaled anesthetic agents. It manifests as a hypermetabolic crisis with unregulated release of calcium from myocyte sarcoplasmic reticulum. Despite the name “malignant hyperthermia,” increased temperature is a late finding and proceeds hypercarbia, tachycardia, acidosis, hyperkalemia, and possibly rhabdomyolysis • NMS is an idiosyncratic reaction to antipsychotic agents, believed to be the result of central dopamine receptor blockade. It presents as altered mental status, rigidity, fever, and dysautonomia. It is more common with neuroleptic agents (haloperidol, droperidol, fluphenazine); however, all classes of antidopaminergics can result in NMS (clonazpine, olanzapine, metoclopramide, promethazine). Although it is not a dose-dependent phenomenon, higher doses are a risk factor. • Endocrine disorders. Hyperthyroidism and thyroid storm represent an abnormal increase in basal metabolic rate with resultant heat products. • Epidural analgesia for labor; patients are more likely to experience hyperthermia and overt clinical fever. Believed to be due to placental and chorioamnio membrane inflammation; however, the mechanism is not completely understood at this time. Because of its potential for neonatal brain injury (cerebral palsy, encephalopathy, learning defects), it can lead to a greater number of Cesarean sections. Additionally, heat transfer to the neonate may result in unnecessary neonatal workup of sepsis. • Fever is caused by exogenous or endogenous pyrogens. Exogenous pyrogens are mainly microbes or their toxins (lipopolysaccharide endotoxin produced by gram-negative bacteria). Endogenous pyrogens are mainly cytokines (IL-1, IL-6, TNF, ciliary neutrotrophic factor). The interaction of pyrogens with hypothalamic circumventricular vascular endothelium is the first step in raising the thermoregulatory set point to febrile levels. – Immediate onset postoperative fever. Occurs in the operating room or a few hours after surgery; they often resolve without therapy and are often unexplained (most often due to trauma, infection, blood transfusion, or due to drugs ). – Acute onset postoperative fever. First week after surgery and is commonly due to surgical site infections, ventilator-associated pneumonia, aspiration, intravascular catheter infections, UTI. – Subacute onset postoperative fever. 1–4 weeks after surgery and includes fever from antibiotic-associated diarrhea, febrile drug reactions, thrombophlebitis. – Delayed onset postoperative fever. Greater than 4 weeks after surgery and includes infections

PREVENTATIVE MEASURES

• Monitoring of temperature intraoperatively can help avoid iatrogenic hyperthermia from excessive warming techniques and assist with early detection of other causes. • In patients with known history or familial history of MH, avoid triggering agents. • Surgical site infections are reduced with aseptic technique; prophylactic antibiotics should be considered. • Central line placement should be performed with maximal barrier sterile technique. • ICU bundles should be implemented to avoid ventilator-associated pneumonia, deep venous thrombosis, and pulmonary embolism.

DIAGNOSIS • History of heat exposure, infection, or the use of certain drugs that interfere with thermoregulation. • Vital signs: Increased temperature; pattern can be helpful. Sinus tachycardia, tachypnea, widened pulse pressure, and hypotension. A temperature >41.5°C and can be observed in severe infections of CNS hemorrhages. The most important causes of severe hyperthermia (>110° F or 40°C) are heat stroke, MH, and NMS. Temperature-pulse dissociation (relative bradycardia) is seen in typhoid fever, brucellosis, and leptospirosis. • Physical exam should be performed to assess for infection. Chest auscultation may reveal rhonchi or reduced sounds; Foley catheter may appear cloudy; wound, central line, and peripheral IV sites may appear erythematous or purulent. • Diagnostic procedures – CBC, basal metabolic panel, electrolytes, BUN, Cr, CK enzymes, and liver enzymes – PT, PTT, and INR because of the risk of DIC – Urine for myoglobinuria – Toxicological screening – CXR may demonstrate pulmonary edema – EKG may reveal sinus tachycardia – Blood, urine, catheter (IV, central line), and sputum cultures – Head CT and lumbar puncture to be performed if CNS etiologies are suspected.

Monitors

• Consider assessment of core temperatures (e.g., rectal). • End-tidal CO2 monitor to detect MH

• Invasive monitoring as dictated by the patient’s clinical status: Arterial line and ABG, CVP, mixed venous oxygen saturation

TREATMENT • Depends on inciting cause • Continuous core temperature monitoring with rectal or esophageal probes • Cold water immersion is the most effective method of rapid cooling, but complicates monitoring and access. Alternatives include application of ice to the axilla, groin, and neck; however, may be poorly tolerated in awake patients. Cold oxygen, cold gastric lavage, cooling blankets, mist of lukewarm water combined with large fans to circulate air may augment evaporative cooling. • Avoidance of alpha-adrenergic agents; vasoconstriction can decrease heat dissipation • Shivering that occurs during cooling methods may be suppressed with meperidine, clonidine, or benzodiazepines as appropriate. • Acetaminophen for fever (infectious, blood products) and some causes of hyperthermia. However, not effective in environmental hyperthermia. There is no role of antipyretic agents in the management of heat stroke since the underlying mechanism does not involve a change in hypothalamic set point.

• Heat stroke, NMS, and MH require ensuring an adequate airway, breathing, circulation; initiation of rapid cooling and treatment of complications. • MH and NMS require immediate discontinuation of triggering agents. MH requires treatment with dantrolene, diuresis, and treatment of acidosis and hyperkalemia. 24-hour support is available from consultants at MH Association of US. 1-800-MH-HYPER. NMS treatment is controversial and use of dantrolene, bromocriptine, and amantadine is largely unsupported. • Infection location and responsible organism should be sought out and treated with antibiotic. Unexplained postoperative fevers without a source of infection should not be treated empirically with antibiotics; often resolve within 48 hours without specific therapeutic interventions. • Central line infections require removal of access site.

FOLLOW-UP Counseling after acute MH. Definitive diagnosis is made by susceptibility testing.

REFERENCES

1. Dinarello CA, Porat R. Pathophysiology and treatment of fever in adults: Up to date 2010. J Endotoxin Res. 2004;10:201–222. 2. essler DI. Perioperative heat balance. Anesthesiology. 2000;92(2):578–596. 3. egal S. Labor epidural analgesia and maternal fever. Anesth Analg. 2010;111(6):1467– 1475. 4. Lee-Chiong TL, Stitt JT. Disorders of temperature regulation. Compr Ther. 1995;21(12):697–704.

ADDITIONAL READING

• Garibaldi RA, Brodine S, Matsumiya S, et al. Evidence for the noninfectious etiology of early postoperative fever. Infect Control. 1985;6:273 • Insler SR, Sessler DI. Perioperative thermoregulation and temperature monitoring. Anesthesiol Clin. 2006;24(4):823–837.

See Also (Topic, Algorithm, Electronic Media Element) • Malignant hyperthermia • Blood transfusions • Ventilator-associated pneumonia • Hypothermia

CODES ICD9 995.86 Malignant hyperthermia

ICD10

• T88.3XXA Malignant hyperthermia due to anesthesia, initial encounter • T88.3XXD Malignant hyperthermia due to anesthesia, subs encntr • T88.3XXS Malignant hyperthermia due to anesthesia, sequela

CLINICAL PEARLS

• Hyperthermia is defined as elevation of core body temperature above the normal diurnal range of 36–37.5°C due to failure of thermoregulation. • Temperature elevation is accompanied by an increase in oxygen consumption and metabolic rate resulting in hyperpnea and tachycardia. • Differential diagnosis is extensive and includes infectious, endocrine, CNS and toxic etiologies. • Management includes initiation of rapid cooling and treatment of complications.

HYPERTHYROIDISM Joe C. Hong, MD

BASICS DESCRIPTION

• Hyperthyroidism is an endocrine disorder that results in an excess of biologically active thyroid hormones: Thyroxine (T4) and triiodothyronine (T3). • Uncontrolled overt hyperthyroidism can lead to thyroid storm. This is a medical emergency that presents with marked tachycardia, hyperthermia, weakness, and altered levels of consciousness and can result in congestive heart failure (CHF) and shock (1).

EPIDEMIOLOGY Incidence

• ∼1:1,000 women per year. • ∼1:10,000 men per year.

Prevalence

General US population:

• Subclinical hyperthyroidism: ∼1%. Over the age of 55 years, it increases to 2% • Overt hyperthyroidism: ∼0.2%

Morbidity

• Thyroid hormone increases bone resorption. Patients with hyperthyroidism have low bone density and are at an increased risk of fracture. • Incidence of atrial fibrillation is 2.5 times greater than in patients without hyperthyroidism (2). • Increased incidence of stroke.

Mortality

Increased risk is attributable to an increased incidence of cardiovascular disease. ETIOLOGY/RISK FACTORS

• Female sex (prevalence ratio of 8:1) • Smokers • Elderly • Positive family history • Other autoimmune disorders • Iodide repletion after iodide deprivation

PATHOPHYSIOLOGY

• Thyroid hormone functions in several capacities, including normal heart, liver, kidney, and

skeletal muscle metabolism, as well as cell differentiation and growth. • T4 and T3 are produced by follicular cells in the thyroid gland in a classic negative feedback system. Thyroid-releasing hormone (TRH; from the hypothalamus) stimulates the release of thyroid-stimulating hormone (TSH; from the anterior pituitary) that in turn stimulates T3 and T4 release (from the thyroid gland). T3 and T4 feedback to inhibit synthesis and release of TRH and TSH. Additionally, high levels of iodide ion can inhibit T4 synthesis and release. • Hormone synthesis involves iodide uptake into the gland, iodination of thyroglobulin, coupling of iodotyrosines to form T4 and T3, and release of thyroid hormone. T4 is converted to T3 intracellularly, which binds to thyroid receptor proteins in the cell nucleus, activates DNA transcription, and increases the rate of RNA synthesis, which ultimately affects protein synthesis. • The clinical manifestations of hyperthyroidism are the exaggerated expressions of the physiologic activities of T3 and T4. • Graves’ disease is an autoimmune disease whereby autoantibodies to TSH receptors bind to and stimulate thyroid hormone production and secretion. • Hashimoto’s thyroiditis is an autoimmune inflammation of the thyroid gland resulting in the release of stored thyroid hormone. After inflammatory “burnout,” the patients become hypothyroid. • Toxic multinodular goiter develops when long-standing thyroid goiters become autonomous, resulting in thyroid hormone production and secretion independent of TSH stimulation. • Other less common causes include radiation thyroiditis, excessive replacement therapy, TSHproducing pituitary adenomas, and ectopic sources of thyroid hormone (struma ovarii).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Intraoperative risk is directly correlated to the severity of hyperthyroidism, and patients scheduled for elective surgery should be made euthyroid prior to surgery. • In patients requiring nonelective surgery, the avoidance of hyperthyroid crisis is the guiding principle of management.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Symptoms are due to the supraphysiologic activity of T3 and T4. • Alertness, emotional lability, nervousness, irritability, poor concentration • Muscular weakness, fatigue • Palpitations • Voracious appetite, weight loss • Hyperdefecation • Heat intolerance

History

Focused on the multiple organ systems affected by the supraphysiologic activities of T3 and T4: Neurological, cardiovascular, hematological, GI, metabolic, pulmonary, and musculoskeletal systems.

Signs/Physical Exam

• Due to the supraphysiologic activity of T3 and T4. • Hyperkinesia, rapid speech • Proximal muscle (quadriceps) weakness, fine tremors • Moist skin, abundant hair; onycholysis • Lid lag, stare, chemosis, periorbital edema, proptosis • Accentuated first heart sound, tachycardia, atrial fibrillation, widened pulse pressure, dyspnea MEDICATIONS

• Strategy should involve inhibition of TSH, TRH, peripheral conversion of T4 to the biologically active T3, and the antagonism of beta-adrenergic activity. • Propylthiouracil (PTU) and methimazole are thioamide derivatives that inhibit the synthesis of thyroid hormones. PTU also has the added advantage of inhibiting the peripheral conversion of T4 to T3 (3). • Potassium iodide and glucocorticoids inhibit the release of thyroid hormones. Glucocorticoids also inhibit peripheral conversion of T4 to T3 (3). • Beta-blockers provide adrenergic antagonism by minimizing inotropism, chronotropism, and the potential for arrhythmias (3). • Medical control of hyperthyroidism may require several weeks.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC: Anemia • Coagulation panel: Thrombocytopenia and decreased vitamin K-dependent clotting factors. • Chemistry panel: Hypercalcemia and hyperglycemia. • EKG and appropriate cardiac evaluation based on history and physical exam. • CT scan in patients with large goiter may be helpful in assessing airway anatomy.

CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular: Increased risk of myocardial ischemia due to increased resting heart rate, stroke volume, and cardiac output. Increase in beta-receptor sensitivity increases the incidence of atrial fibrillation, premature ventricular contractions, and high-output CHF. • Pulmonary: Weakness of respiratory muscles leading to a reduction in vital capacity and lung compliance. • GI: Impaired drug absorption secondary to rapid GI transit. Hyperdefecation and diarrhea leads to hypokalemia and hypovolemia. • Hematological: Anemia, thrombocytopenia, and decreased vitamin K-dependent factors. • Metabolic: Hypercalcemia from increased bone resorption and impaired glucose tolerance due to up-regulation of beta-adrenergic receptors. • Musculoskeletal: Increased risk of osteopenia and fracture due to bone resorption. Generalized weakness in skeletal muscles from metabolic derangements and the catabolic state associated with severe hyperthyroidism. CIRCUMSTANCES TO DELAY/CONDITIONS

• Thyroid storm is a medical emergency and must be treated prior to surgery. • Signs and symptoms as well as concomitant organ dysfunction must be optimized prior to elective surgery.

TREATMENT PREOPERATIVE PREPARATION Premedications

Patients usually have high anxiety. Appropriate use of anxiolytics/sedatives should be balanced against the presence of airway compromise in patients with goiter. INTRAOPERATIVE CARE Choice of Anesthesia

• Deep general endotracheal anesthesia for thyroidectomy. • Anesthesia technique for nonthyroid surgery should be dictated by the type of surgery and planned position, as well as surgeon/anaesthetist preference. Monitors

• Standard ASA monitors. • Invasive monitoring as dictated by planned surgery and patient comorbidities. • EMG endotracheal tube per surgeon request for thyroid surgery.

Induction/Airway Management

• Large goiter can cause tracheal deviation, compression, and tracheomalacia. Preoperative CT of the neck may help to delineate the severity of airway compromise. Awake fiberoptic intubation should be considered if there is a high suspicion of airway compromise. Care should be taken to blunt the adrenergic effect of awake intubation in these patients with sensitized adrenergic tone. • Induction drug should be chosen carefully based on comorbidities. Ketamine should be used with care as this drug may increase adrenergic tone in these sensitized patients. • Succinylcholine or nondepolarizing muscle relaxants with sympathomimetic effects or histamine release should be used with caution. • Patients with exophthalmos require careful application of ointment to the cornea and secure taping of the eyelids. Maintenance

• The avoidance of a thyroid crisis is the guiding principle in managing hyperthyroid patients. • Maintenance of a deep level of surgical anesthesia is prudent. • Medications that increase sympathetic tone should be avoided. Examples include pancuronium, ephedrine, and meperidine. • Anticholinergics for reversal of neuromuscular blockade may also increase sympathetic tone. Careful attention must be paid to prevent an exaggerated sympathetic response. Glycopyrrolate has less chronotropic effect than atropine and therefore may be the preferred choice.

Extubation/Emergence

• After a thyroidectomy: – Coughing/bucking on emergence should be minimized to decrease the likelihood of neck hematoma formation. Preintubation tracheal lidocaine can provide airway analgesia. – Communication with the surgeon regarding likelihood of recurrent laryngeal nerve injury needs to take place prior to emergence and extubation.

POSTOPERATIVE CARE BED ACUITY

Patients with poorly controlled hyperthyroidism and significant comorbidities should be monitored in the ICU setting. COMPLICATIONS

• Thyroid storm is a rare medical emergency that typically develops postoperatively in patients with hyperthyroidism. Thyroid storm may be difficult to distinguish from malignant hyperthermia, neuroleptic malignant syndrome, or pheochromocytoma. Mortality may be as high as 20–30% (4). Management of thyroid storm involves: – Oxygen, airway protection, hyperventilation, aggressive fluid replacement. – Beta-adrenergic blockade, typically with a short-acting titratable beta-blocker like esmolol. – PTU, methimazole, potassium iodide, corticosteroids. – Cooling measures involving cool IV fluids, cooling blankets, nasogastric, or bladder lavage. – Plasmapheresis or peritoneal dialysis can remove excess thyroid hormones (5). • Thyroidectomy – Airway compromise (most common) from hematoma, airway edema, tracheomalacia, hypocalcemia from hypoparathyroidism, and partial bilateral recurrent laryngeal nerve injury. The RLN innervates all intrinsic laryngeal muscles except the cricothyroid (SLN). Specifically, the RLN innervates a number of adductors, and a single abductor (posterior cricoarytenoid muscles). Injury to the abductor component can result in unopposed adduction (including from the SLN innervated cricothyroid). Complete transection will result in the affected vocal cord lying in the midline (injury to the adductors and abductors). – Injury to the nearby carotid artery can result in massive bleeding and possible stroke – Intraoperative carotid sinus irritation may lead to hemodynamic fluctuations and bradyarrhythmias – Occult pneumothorax can result from lower neck surgical dissection

REFERENCES

1. Singer PA, et al. Treatment guidelines for patients with hyperthyroidism and hypothyroidism. Standards of care committee, American Thyroid Association. JAMA. 1995;273:808. 2. herman SI, et al. Clinical and socioeconomic predispositions to complicated thyrotoxicosis:

A predictable and preventable syndrome? Am J Med. 1996;101:192. 3. ooper DS. Antithyroid drugs. N Engl J Med. 2005;352:905.

4. ayak B, et al. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006;35:663. 5. etry J, et al. Plasmapheresis as effective treatment for thyrotoxic storm after sleeve pneumonectomy. Ann Thorac Surg. 2004;77:1839.

ADDITIONAL READING

• Franklyn JA. The management of hyperthyroidism. N Engl J Med. 1994;330:1731. • Graham GW, et al. Perioperative management of selected endocrine disorders. Int Anesthesiol Clin. 2000;38:31. See Also (Topic, Algorithm, Electronic Media Element)

• Hypothyroidism • Vocal cord palsy

CODES ICD9 • 242.90 Thyrotoxicosis without mention of goiter or other cause, and without mention of thyrotoxic crisis or storm • 242.91 Thyrotoxicosis without mention of goiter or other cause, with mention of thyrotoxic crisis or storm ICD10 • E05.80 Other thyrotoxicosis without thyrotoxic crisis or storm • E05.90 Thyrotoxicosis, unsp without thyrotoxic crisis or storm • E05.91 Thyrotoxicosis, unspecified with thyrotoxic crisis or storm

CLINICAL PEARLS

• Intraoperative risk is directly correlated to the severity of hyperthyroidism. • Preoperative medical management involves inhibition of thyroid hormone synthesis, release, and peripheral conversion. Commonly used medications include PTU, methimazole, potassium iodide, glucocorticoids, and beta-adrenergic blockade. • Careful airway management and possible awake fiberoptic intubation may be indicated in patients with large goiter. • The avoidance of thyroid crisis by maintaining a deep level of surgical anesthesia while minimizing exposure to sympathomimetic medications is the guiding principle in managing hyperthyroid patients. • Postoperative complications are usually related to airway compromise. Causes include hematoma, airway edema, tracheomalacia, and partial bilateral recurrent laryngeal nerve injury.

• Thyroid storm is a medical emergency with high mortality. Decisive emergent management is crucial.

HYPERTROPHIC CARDIOMYOPATHY Adam M. Thaler, DO

BASICS DESCRIPTION

• Hypertrophic cardiomyopathy (HCM) describes idiopathic, abnormal left ventricle hypertrophy (LVH) (specifically an asymmetric septum). • The obstructive variant, commonly referred to as hypertrophic obstructive cardiomyopathy (HOCM) can impair LV ejection of blood to the systemic circulation. EPIDEMIOLOGY Prevalence

• In the US population: 1:500 people. It is the most common genetic cardiovascular disease • Males > females • Most commonly presents in the third decade of life, but it may present in persons of any age. Morbidity

Arrhythmias: Atrial fibrillation, atrial flutter, ventricular ectopy, ventricular tachycardia, and ventricular fibrillation (one of the highest-risk groups for ventricular fibrillation) Mortality

• Most common cause of sudden cardiac death (SCD) • Annual mortality rates overall are ∼1% per year. • Children with HCM have an SCD risk of up to 6% per year. • Some adult subgroups 6% per year (2) • In competitive athletes, there are <100 deaths a year (equates to about 1 death per 220,000 athletes). ETIOLOGY/RISK FACTORS

Genetic predisposition. HCM is an autosomal dominant trait that causes mutations in sarcomeric proteins. This results in structural abnormalities: A catenoid (curved surface with the property of net zero curvature at all points) configuration of the septum, which results in myocardial cell hypertrophy and disarray. PATHOPHYSIOLOGY

• The hypertrophied myocardium exhibits – Decreased lusitropy. Abnormalities of the cardiac microcirculation deplete energy stores essential for the sequestration of calcium during diastole, resulting in subendocardial ischemia. This causes persistent interaction of the contractile elements during diastole and increased diastolic stiffness.

– Increased ejection fraction (EF) that is commonly >80% despite diastolic dysfunction and decreased compliance. – Increased myocardial oxygen demand. Similar to LVH and aortic stenosis (AS), there is greater muscle mass. – Decreased myocardial oxygen delivery. Hypertrophied muscle creates more resistance to perfusion. – Decreased wall tension. T = (R × ΔP)/H, where T = tension, R = radius, ΔP = pressure gradient, and H = wall thickness – However, over time, the thickened heart may become weak and ineffective causing ventricular enlargement, systolic dysfunction (decreased EF), and dilated cardiomyopathy (increased wall tension). • Abnormal sympathetic stimulation: Heightened responsiveness of the heart to the excessive production of catecholamines or the reduced neuronal uptake of norepinephrine might exacerbate HCM. • Abnormally thickened intramural coronary arteries: These do not dilate normally, which leads to myocardial ischemia and, with time, can progress to myocardial wall fibrosis. • Obstructive disease variant. Systolic anterior motion (SAM) of the anterior leaflet of the mitral valve can result in dynamic left ventricular outflow tract (LVOT) obstruction when the ventricle size decreases. Previously believed to result from high velocity flow and a Venturi effect on the anterior leaflet of the mitral valve, but recent echocardiographic evidence indicates that SAM is a low velocity phenomenon and that drag (the pushing force of flow), not the Venturi effect, is the dominant hydrodynamic force on the mitral leaflets. LVOT obstruction can be present at rest or can be induced with a Valsalva maneuver. • Changes in electrical and muscular conduction and alterations of coronary perfusion increase the incidence of atrial and ventricular arrhythmia and risk for SCD.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintenance of cardiac output, coronary perfusion, and prevention of cardiac decompensation are the primary goals. • Monitor and maintain normal sinus rhythm. • In patients with HOCM, decrease “emptying” of the heart by: – Maintaining adequate intravascular volume – Maintaining appropriate systemic vascular resistance (SVR): Avoid vasodilators, provide vasoconstriction – Decreasing inotropy and chronotropy: Avoid inotropes and control sympathetic response with adequate anxiolytics and narcotics.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Usually asymptomatic • Dyspnea is seen in 90% of symptomatic patients; it results from the high LV filling pressures (decreased compliance and causes pulmonary edema) • Syncope from inadequate CO upon exertion

• Other: Fatigue, dizziness, palpitation, tachydysrhythmias, heart failure, and SCD

History

• Family history of cardiac disease or sudden death • Commonly diagnosed after symptomatic exercising or during workup for diastolic or systolic CHF or angina. Signs/Physical Exam

• Systolic ejection crescendo–decrescendo murmur heard best between the apex and left sternal border. Murmur/gradient increases with any decrease in preload (Valsalva, diuretics, standing) or decrease in afterload (vasodilation). • Double or triple apical impulse from forceful LA contraction against highly noncompliant LV. • Bisferiens carotid pulse due to obstruction • Brockenbrough–Braunwald–Morrow. Describes an increase in peak-systolic gradient combined with a decrease in pulse pressure after an extrasystolic beat. TREATMENT HISTORY

• Prophylactic ICD or pacemaker (allows high dose beta-blockade) • Septal myectomy. The removal of a small amount of cardiac muscle from the ventricular septum. Performed when severe symptoms of CHF or outflow tract gradients are >50 mm Hg. • Nonsurgical percutaneous transluminal septal ablation. Alcohol is injected into septal branches of the LAD causing therapeutic infarction within septal myocardium to decrease hypertrophy and LVOT obstruction. Requires a permanent pacemaker 30% of the time. MEDICATIONS

• Beta-blockers are first-line therapy. By decreasing the heart rate, diastole is prolonged (increased time for passive ventricular filling, perfusion of the left ventricle, decreased oxygen consumption). In patients with HOCM, they are useful by decreasing contractility/inotropy. • Calcium channel blockers (CCB) improve ventricular filling by increase LV compliance. In patients with HOCM, they are useful by decreasing LVOT obstruction. • Amiodarone for prophylaxis against arrhythmias

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• EKG: Left ventricular hypertrophy • Echocardiogram: Myocardial hypertrophy, EF >80% due to hypercontractile condition; assessment of mitral valve and presence of SAM • Catheterization: Increased LV end-diastolic pressures (LVEDP) and LV-aorta pressure gradients between LV and aorta • Definitive diagnosis: Endomyocardial biopsy showing myocardial fiber disarray and DNA analysis

CONCOMITANT ORGAN DYSFUNCTION

• Hypertension • Pulmonary hypertension, congestion, pleural effusion • Arrhythmias

CIRCUMSTANCES TO DELAY/CONDITIONS Uncontrolled arrhythmias CLASSIFICATIONS

Obstructive versus nonobstructive • The obstructive variant has historically been known as idiopathic hypertrophic subaortic stenosis (IHSS) and asymmetric septal hypertrophy (ASH). It is more commonly referred to today as hypertrophic obstructive cardiomyopathy (HOCM). • The nonobstructive variant (apical HCM) is also called Yamaguchi syndrome.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Continue beta-blockers or CCB perioperatively • Relieve anxiety • Expansion of intravascular volume to minimize the adverse effects of positive pressure ventilation (decreased preload in the presence of diastolic dysfunction) and to decrease LVOT obstruction in patients with HOCM. • Manage pacemaker/defibrillator appropriately

INTRAOPERATIVE CARE Choice of Anesthesia

• Dependent on type of surgery, patient comorbidities, and physical exam. • In patients with HOCM, the use of spinal anesthesia is relatively contraindicated due to the rapid decrease in SVR. Pregnancy Considerations

In the 3rd trimester, increases in inotropy, aortocaval compression, sympathetic stimulation, and blood loss during delivery can result in cardiac decompensation. Regional, neuroaxial, and general anesthesia have been safely administered for labor. Monitors

• Standard ASA monitors • Additional monitoring depends on the surgery. Arterial line can help assess rapid hemodynamic changes and the potential for hypotension and MI; may be placed preoperatively. If the patient is at a high risk for decompensation, consider a pulmonary artery catheter to monitor the right and LV function (may overestimate true volume status

as a result of reduced diastolic compliance). • Transesophageal echocardiogram (TEE) may be indicated to evaluate myocardial function and detect regional wall motion abnormalities.

Induction/Airway Management

Administration of volatile anesthetic or beta-blocker before laryngoscopy can blunt the sympathetic response. Maintenance

• Hypotension. – Decreased coronary perfusion pressure can result in ischemia of the hypertrophic myocardium. – In patients with HOCM, decreases in SVR should be avoided. Volatile and IV agents can decrease SVR; avoid excessive doses, consider concomitant alpha agonism (low dos phenylephrine infusion). – Avoid drugs with beta-activity (ephedrine, epinephrine) as they can increase myocardial contractility and HR. • Pain, awareness, and stimulation can increase the HR and contractility (increases oxygen demand). • Ventilation. Positive-pressure ventilation can significantly decrease preload. In patients with HOCM, this can result in dynamic LVOT obstruction. Smaller tidal volumes or avoidance of PEEP may be considered. • Drugs. Caution with histamine-releasing medications or those that increase HR (vancomycin, morphine, etc.). In patients with HOCM, vasodilators should be used cautiously to treat hypertension as they can decrease SVR; alternatively, consider beta blockade. • Fluids. Prompt replacement of blood loss and titration of IV fluids is important; aggressive replacement may result in pulmonary edema secondary to diastolic dysfunction. • Arrhythmias. Immediate pharmacologic or electrical cardioversion • Laparoscopy. Abdominal insufflation can cause severe hypotension and preload reduction; insufflate slowly and maintain pressure <15 mm Hg.

Extubation/Emergence

All factors that stimulate sympathetic nervous system (SNS) such as pain, shivering, anxiety, hypoxia, and hypercarbia should be avoided.

POSTOPERATIVE CARE BED ACUITY

• Patients may benefit from ICU or telemetry given the high risk of cardiac complications; the postoperative period is marked by increased myocardial oxygen demand, increased catecholamine levels, hypoxia, hypercoagulability, and large fluid shifts. MI occurs more frequently postoperatively. • Consider supplemental oxygen (nasal cannula, face mask). • Good analgesia can decrease SNS activity; consider PCA, epidural, or regional as

appropriate.

COMPLICATIONS

• In patients with HOCM, LV outflow tract obstruction from a variety of perioperative events (hypovolemia, hypotension, increased inotropy) can cause acute decompensation. • Arrhythmias

REFERENCES

1. Luckner G, et al. Systolic anterior motion of the mitral valve with left ventricular outflow tract obstruction: Three cases of acute perioperative hypotension in noncardiac surgery. Anesth Analg. 2005;100(6):1594–1598.

2. ingh KV, Shastri C, Raj V, et al. Anaesthetic management of a case of hypertrophic obstructive cardiomyopathy for non cardiac surgery. Internet J Anesthesiol. 2007;12(2). 3. Thompson R, Liberthson R, Lowenstein E. Perioperative anesthetic risk of noncardiac surgery in hypertrophy obstructive cardiomyopathy. JAMA. 1985;254(17):2419–2421.

ADDITIONAL READING

• Dilated cardiomyopathy • Left ventricular end-diastolic pressures • Ventricular hypertrophy

CODES ICD9 • 425.11 Hypertrophic obstructive cardiomyopathy • 425.18 Other hypertrophic cardiomyopathy ICD10 • I42.1 Obstructive hypertrophic cardiomyopathy • I42.2 Other hypertrophic cardiomyopathy

CLINICAL PEARLS

• SAM can be induced in an otherwise healthy patient who comes in with severe hemorrhage and is administered epinephrine. The catecholamine surge causing a hypercontractile state and the underfilled ventricle presents similarly to HOCM. Other causes of LVOT obstruction include sepsis, excess SNS, pericardial tamponade, aortic valve replacement (AVR) for AS, or mitral valve replacement (MVR). • SAM may be an unrecognized cause of acute perioperative cardiovascular collapse. Acute treatment includes volume infusion and vasopressors.

HYPOGLYCEMIA

Michael S. Green, DO Poovendran Saththasivam, MD

BASICS DESCRIPTION

• Hypoglycemia is defined as a serum glucose <70 mg/dL. • Tight glucose control has been shown to improve outcomes in critically ill patients; however, hypoglycemia is the most common complication of insulin therapy and has more immediate and direct deleterious effects. • Additionally, severely ill, elderly patients, and neonates have an increased susceptibility to the deleterious effects of hypoglycemia (permanent neurologic damage and death). EPIDEMIOLOGY Incidence

• Rare in persons not treated for diabetes. • Severe hypoglycemia (episodes per 100 patients/year) – Type 1 diabetic: 11.5 – Type 2 diabetic treated with oral hypoglycemic agents: 0.05 – Type 2 diabetes treated with insulin: 11.8 – Elderly patients: 2 • Neonates: 1–5 per 1,000 live birth; higher incidence in large-for-gestational age, preterm, and intrauterine growth restricted (IUGR) infants, as well as those born to diabetic mothers. Morbidity

Increased when intensive insulin therapy (IIT) in the medical intensive care unit (ICU) is implemented; particularly in patients with renal or hepatic failure. ETIOLOGY/RISK FACTORS

• Iatrogenic hypoglycemia – Overdose of insulin or other antidiabetic drug ingestion. – Decreased exogenous glucose intake (missed meals/snack or after overnight fasting). • Alcohol ingestion • Side effect of certain drugs: Haloperidol, pentamidine, quinine, and nonselective betablockers. • Severe illness • Tumors: Pancreatic islet cell adenoma or carcinoma, hepatoma, and sarcoma • Adrenal insufficiency • Autoimmune processes • Increased sensitivity to insulin following exercise, weight loss, or due to insulin sensitizers. • Renal failure: Decreased clearance of insulin

• Neonates – Preterm delivery – Transient hypoglycemia of the newborn – IUGR – Sepsis – Hypothermia – Birth asphyxia – Inborn errors of metabolism – Hepatic enzyme deficiencies – Transplacental exposure to maternal hypoglycemic medications • Elderly: Frail, polypharmacy, and multiple hospital admissions.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Glucose is a principal energy substrate for the body; for the brain, it is the sole energy substrate. • Glucose is synthesized from gluconeogenesis (from the metabolism of pyruvate, lactate, glycerol, and glucogenic amino acids) and glycogenolysis that results from the breakdown of glycogen. • In normal glucose homeostasis, blood glucose levels are tightly regulated by insulin, glucagon, epinephrine, and cortisol. The liver is the principal storage site for glucose in the form of glycogen. • A decrease in blood glucose level will cause – Drops in endogenous insulin production – Release of epinephrine, glucagon, growth hormone, and cortisol that act as counterregulatory hormones. – An increase in hepatic glucose production – A decrease in peripheral utilization of glucose – Neurogenic and neuroglycopenic symptoms • Diabetes – Type 1, or insulin-dependent, diabetics have reduced or absent insulin secretion. In addition, they have an impaired release of counterregulatory hormones such as glucagon and epinephrine. – In type 2 diabetes, patients are capable of generating and secreting insulin, but peripheral tissues are resistant to its effects. There is a lower risk of hypoglycemia compared to type 1 diabetes, potentially due to the sustained ability to secrete counterregulatory hormones. – Exogenous insulin administration and oral antihyperglycemic medications (e.g., sulfonylureas) can cause iatrogenic hypoglycemia. • Neonatal hypoglycemia can cause seizure and permanent brain damage. The brain utilizes glucose as the sole substrate of energy. In the rapidly growing neonatal brain, cerebral consumption comprises nearly 90% of their total glucose consumption; however, neonates are susceptible to hypoglycemia due to – Inadequate hepatic glycogen reserve – Immaturity of the liver in synthesizing glucose (hepatic gluconeogenesis). – Relative hyperinsulinism in infants of diabetic mother – Inherited disorders of metabolism

– Impaired release of counterregulatory hormones • Evidence is suggesting that the benefits of tight glucose control may be outweighed by the potential harm of hypoglycemia. – The ACCORD trial revealed that intensive glucose control in patients with type 2 diabetes mellitus (HBA1C <6%) is associated with increased mortality and no reduction in adverse cardiovascular events. – The NICE SUGAR study revealed that in the ICU patients treated with IIT had increased mortality. IIT was defined as a blood glucose aim of 81–106 g/dL; the conventional group was defined as a blood glucose aim of <180 g/dL. – Several studies report that maintaining a stable glucose level is equally important to the absolute glucose values. Fluctuations in glucose control lead to oxidative stress that cause macrovascular complications. • Cardiac surgical patients, particularly those requiring prolonged intensive care admissions, are an exception; they show a clear benefit from strict glycemic control.

PREVENTATIVE MEASURES

• Diabetics. Preoperative assessment of glucose control, type and dose of medications, frequency of hypoglycemia, and current HBA1C level is needed. • On the day before surgery – Oral medications are usually dosed normally – Long or intermediate-acting insulin can be taken in usual doses while on a normal diet. Evening of night doses are normally decreased. – If hypoglycemic while NPO, treat with 15–20 gm of glucose. Options include clear liquids, in the form of sugary drinks and fruit juices, sodas, or electrolyte solutions. – Blood sugar checks should be done frequently when NPO. • On the morning of surgery – In type 2 diabetics, oral medications and short-acting injectables should be withheld. – Insulin pumps should be maintained at a basal rate and short-acting insulin should be withheld. – For morning cases, hold intermediate-acting insulin or give a percentage of the dose calculated as below: Fraction = [(dosing interval in hours) – (hours of fast during interval)]/(dosing interval in hours) – For cases later in the day, maintain a basal rate for patients on an insulin pump and for patients on intermediate insulin, give a percentage of the dose based on the formula above. • In the recover room or hospital ward, resume oral hypoglycemic agents and insulin with food. • Hyperglycemia in the perioperative period. Correction doses of ultra short-acting insulin: 1– 4 U IV typically decreases blood sugar by 50 mg/dL.

DIAGNOSIS • Signs and symptoms are the result of: – Adrenergic excess; diaphoresis, tachycardia, palpitations, or tremulousness/shakiness.

– Neuroglycopenia; headache, confusion, mental sluggishness, seizures, or coma • In anesthetized patients all symptoms may be masked; unexplained tachycardia can sometimes present. Blood glucose monitoring is confirmatory. • In awake patients – Severe hypoglycemia: Requires the presence of another person to actively administer carbohydrates, glucagon, or other treatments. It does not require documentation of the plasma glucose level. Symptoms resolve after restoring normal blood glucose. – Documented symptomatic hypoglycemia: The presence of hypoglycemic symptoms along with a documented blood glucose <70 mg/dL. – Asymptomatic hypoglycemia: Absence of hypoglycemic symptoms but documented blood glucose <70 mg/dL. – Probable symptomatic hypoglycemia: Presence of hypoglycemic symptoms with unknown blood glucose level. – Relative hypoglycemia: Presence of hypoglycemic symptoms but blood glucose level >70 mg/dL. – Whipple’s triad: Hypoglycemic symptoms, symptoms relieved after glucose intake, and documented low blood glucose level. • Elderly patients display fewer hypoglycemic symptoms. • Women respond less strongly to hypoglycemia than men.

DIFFERENTIAL DIAGNOSIS • Seizure • Vasovagal attack • Cardiac arrhythmia • Panic attack

TREATMENT • Fully conscious patient – Oral glucose (15–20 g), sucrose or sugar containing fluid, orange juice, or a piece of fruit. – Ensure adequate subsequent food intake to prevent recurrence. • Impaired consciousness – Administer Dextrose 50% 25–50 mL IV until there is a return of consciousness or normal blood glucose level. Then start a Dextrose 5% (D5W) or Dextrose 10% (D10W) infusion and titrate to effect. – In severe hypoglycemia, glucagon 1 mg IV may be administered. In patients without IV access, glucagon IM or SQ may be given. • Symptomatic infants – D10W 2 mL/kg IV bolus, followed by an infusion rate of 6–8 mg/kg/min. To achieve this rate: D5W: IV rate (in mL/hr) = 8.4 × body weight (kg) D10W: IV rate (in mL/hr) = 4.2 × body weight (kg) • Anesthetized patient – Administer Dextrose 50% 25–50 mL IV, followed by repeat testing and careful observation

with possible infusion. If glucose levels remain low, repeat the bolus and consider starting an infusion.

FOLLOW-UP • Anesthetic management should aim to minimize the stress response during the intraoperative and postoperative period. Consider adequate pain relief and prophylaxis for nausea and vomiting. • Dexamethasone can elevate blood glucose for several hours, with a maximum blood glucose noted 120 minutes after dosing. • Autonomic neuropathy can cause swings in hemodynamic response during induction.

REFERENCES

1. Zammitt NN, Frier BM. Hypoglycemia in type 2 diabetes. Diabetes Care. 2005;28:2948– 2961. 2. ryer PE. Management of hyperglycemia in type 2 diabetes: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2007;30(1):190–192. 3. Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: A report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005;28(5):1245–1249. 4. Gabriely I, Shamoon H. Hypoglycemia in diabetes: Common, often unrecognized. Cleve Clin J Med. 2004;71(4):335–342. 5. Wintergerst KA, Buckingham B, Gandrud L, et al. Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unit. Pediatrics. 2006;118(1):173–179. 6. NICE-SUGAR Study Investigators, Finfer S, Chittock DR, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283– 1297. 7. Vann MA. Perioperative management of ambulatory surgical patients with DM. Curr Opin Anaesthesiol. 2009;22(6):718–724.

ADDITIONAL READING

• Joshi GP, Chung F, Vann MA, et al.; Society for Ambulatory Anesthesia. Society for Ambulatory Anesthesia consensus statement on perioperative blood glucose management in diabetic patients undergoing ambulatory surgery. Anesth Analg. 2010;111(6):1378–1387. • Moghissi ES, Korytkowski MT, Dinardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009;32:1119–1131. • The DCCT Research Group: Hypoglycemia in the Diabetes Control and Complications Trial. Diabetes. 1997;46:271–286.

See Also (Topic, Algorithm, Electronic Media Element) • Hyperglycemia • Diabetes mellitus

CODES ICD9 251.2 Hypoglycemia, unspecified ICD10 E16.2 Hypoglycemia, unspecified

CLINICAL PEARLS

• Hypoglycemia is the main obstacle in achieving good glycemic control in patients with diabetes. • Cardiac surgical patients benefit from strict glucose control, but the aim for most ICU patients is a stable blood glucose <180 g/dL. • Glucose is the sole energy substrate for the brain; furthermore, there are no stores to protect against a decreased supply.

HYPOKALEMIA

Matthew C. Gertsch, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION • Hypokalemia is defined as a plasma potassium (K+) concentration <3.5 mEq/L (normal 3.5–5 mEq/L). Causes include K+ loss or intracellular shifting. Symptoms range from arrhythmias to myalgias to respiratory depression. • Hypokalemia may be a poor indicator of total body stores because of its asymmetric body distribution. Ninety-eight percent of the body’s potassium is located intracellularly (75% in muscle, 6% in red blood cells, and 5% in the liver). The remaining 2% is located in the intravascular and extracellular compartments (2). • Patients commonly present for surgery with low K+ levels, which is the most common electrolyte abnormality in hospitalized patients. Anaesthetists must be able to determine when and how a patient should be managed with such abnormalities.

PHYSIOLOGY PRINCIPLES

• The majority of the body’s potassium stores are located intracellularly. • The membrane resting potential is an electrochemical gradient that plays a role in transport, signal transduction, myocardial pacemakers and contraction, and cell volume homeostasis. Consequently, there are several mechanisms that serve to maintain intravascular concentrations within a tight range. – The Na+–K+–ATPase enzyme pump (embedded in the cell membrane) moves 3 Na+ ions extracellularly and 2 K+ ions intracellularly. The exchange requires the expenditure of 1 adenosine triphosphate (ATP). The electrochemical gradient is manifested by an intracellular concentration of 150 mEq/L (intravascular concentration is ∼3.5–5 mEq/L). • Additional mechanisms: K+ concentrations between the two compartments are also affected by pH, insulin, and catecholamines or sympathomimetics with beta-adrenergic receptor activity. – pH: The Na+–H+ ion exchange facilitates buffering against alkalemia or acidemia. In alkalemia, H+ ions move extracellularly to offset the disturbance and Na+ moves intracellularly. This increase in intracellular Na+ stimulates the Na+–K+–ATPase, which results in a secondary intracellular shift of K+. Conversely, in acidemia, H+ ions move intracellularly, in exchange for Na+ moving extracellularly. This reduces intracellular shifting of K+ via the Na+–K+–ATPase (can result in hyperkalemia). – Insulin: Activates the Na+–K+–ATPase in cells, causing an intracellular shift of K+. – Beta-adrenergics: Activate adenylyl cyclase and increase cAMP levels, which then activate protein kinase A. Results in activation of calcium-gated K+ channels as well as Na+–K+–

ATPase. • K+ excretion: In addition to intracellular shifting, K+ levels are also regulated by the kidneys (90%), the gastrointestinal (GI) tract, and sweat. Aldosterone, a mineralocorticoid, lowers plasma K+ concentration at several levels in the renal tubule.

ANATOMY

• Although the resting membrane potential is maintained by the Na+–K+–ATPase, certain cells exert their functional capacity via depolarization. – Pacemaker cells spontaneously depolarize to produce an electrical signal that travels to conduction cells and adjacent myocardial muscle cells in a domino-like fashion. Repolarization (Phase 3) is primarily via potassium efflux. – Myocardial muscle cells depolarize in response to adjacent pacemaker or muscle cells. Electrical depolarization is coupled to mechanical contraction and blood being pumped. Repolarization is mediated via potassium efflux; however, it is divided into an early (Phase 1) and late (Phase 3) phase by an extended plateau. – Nerve cells communicate and transmit their signal via electrical signaling that involves changes in resting membrane potential. Repolarization occurs via potassium efflux.

DISEASE/PATHOPHYSIOLOGY

• Hypokalemia is defined as a serum [K+] <3.5 mEq/L. This disturbance is the result of either reduced total body stores or redistribution into the intracellular space. • Reduced total body stores may result from reduced intake or increased excretion (renal or extrarenal). – Reduced intake: The minimum daily requirement is 40–50 mEq/day – Increased renal excretion: Type I and II renal tubular acidosis, diuretic therapy, carbonic anhydrase inhibitors, ureterosigmoidostomy, posthypercapnia, increased mineralocorticoid activity (aldosterone), and hemodialysis – Increased extrarenal excretion: Diarrhea, vomiting and nasogastric suction, increased sweat loss, and laxative abuse • Intracellular shifting can occur perioperatively via alkalemia, exogenous insulin administration, and beta-adrenergics. – Alkalemia: Hyperventilation results in hypocarbia, and can be caused perioperatively by controlled mechanical ventilation (increased respiratory rate or tidal volume), stimulation, or pain. Another cause is excessive bicarbonate administration. – Exogenous insulin may be administered for glucose control. Hyperalimentation may increase endogenous insulin release. – Beta-adrenergics may be administered as catecholamines or sympathomimetics (epinephrine, dobutamine, isoproterenol, and ephedrine). Nebulizers and inhalers for the treatment of COPD or asthma. Thyrotoxicosis causes excessive beta-adrenergic stimulation. • Clinical manifestations of hypokalemia result from hyperpolarization of cell membranes, as well as from prolongation of action potentials and refractory periods. Thus, it primarily affects cardiac, skeletal muscle, GI, and renal systems. – Cardiac: Dysrhythmias (premature atrial contractions, premature ventricular contractions,

AV block, ventricular tachycardia, ventricular fibrillation), conduction defects (increased PR and QT intervals, reduced T wave amplitude, T wave inversion or U waves, and ST segment depression), and potentiation of digitalis toxicity. – Skeletal muscle: Weakness, paralysis, rhabdomyolysis, fasciculations, and tetany (typically do not manifest until the serum [K+] is <3 mEq/L) – GI: Ileus, constipation – Renal: Metabolic alkalosis, nephrogenic diabetes insipidus, impaired urinary concentrating abilities, increased NH3 production, and hypokalemic nephropathy.

• Acute changes are less well tolerated than chronic changes. • Correlation between serum and total body K+ is not exact and may be difficult to extrapolate. It is estimated that in chronic hypokalemia reduced plasma levels of 1 mEq/L can equal a total body deficit of 200–400 mEq (1).

PERIOPERATIVE RELEVANCE

• Mild hypokalemia (3.0–3.5 mEq/L) does not typically require urgent correction (2). • [K+] <3.0 mEq/L often requires K+ replacement. Of note, values greater than or equal to 2.6 mEq/L have not been shown to increase morbidity or mortality in patients undergoing anesthesia. • [K+] between 2.0 and 2.5 mEq/L are likely to cause arrhythmias and muscular weakness; furthermore, it can potentiate the effects of neuromuscular blocking agents and can delay recovery. • Potassium replacement. Oral and IV preparations are available. Perioperative correction often involves IV KCl preparations. The maximum recommended rate of infusion is 10–20 mEq/hour (peripheral IV: 10 mEq/hour; central line access 20 mEq/hour). Higher rates of administration carry the risk of hyperkalemia or arrhythmias. • Magnesium replacement should be concurrently performed. • Delay or proceed? The decision to delay for further optimization versus proceeding depends upon: – Urgency of surgery. Urgent or emergent surgery may be performed with careful EKG monitoring and avoidance of hyperventilation, alkalosis, and beta-adrenergics. K+ replacement should be undertaken. In the event that arrhythmias or EKG changes manifest, boluses of 1 mEq may be administered while monitoring for resolution. – Acute versus chronic onset. When patients present preoperatively with hypokalemia, a determination of its onset should be attempted. Review old laboratory values. – Clinical manifestations should be assessed – EKG changes – Need for perioperative hyperventilation. Intracranial surgical procedures may require intracranial pressure optimization via hyperventilation (hypocarbia). Additionally, the use of mannitol or furosemide to provide “brain relaxation” can further decrease potassium levels (excreted by the kidneys). Attempts to correct potassium should be undertaken prior to surgery. In the event that the patient’s clinical condition deteriorates, proceed as discussed above for urgent/emergent surgery. – Need for beta-adrenergic agents

REFERENCES

1. Lim S. Approach to hypokalemia. Acta Med Indones. 2007;39(1):56–64.

2. Katerinis I, Fumeaux Z. Hypokalemia: Diagnosis and treatment. Rev Med Suisse. 2007;3(101):579–582.

ADDITIONAL READING

• Lin SH, Halperin ML. Hypokalemia: A practical approach to diagnosis and its genetic basis. Curr Med Chem. 2007;14(14):1551–1565.

See Also (Topic, Algorithm, Electronic Media Element) • Hyperkalemia • Buffering systems • Cardiac action potential • QT prolongation

CODES ICD9 276.8 Hypopotassemia ICD10 E87.6 Hypokalemia

CLINICAL PEARLS

• Hypokalemia is the most common perioperative electrolyte abnormality. May manifest as arrhythmias, conduction disturbances, muscle weakness, potentiation of neuromuscular blocking agents, and delayed awakening. • Anaesthetists must determine whether to delay surgery in order to optimize plasma levels or proceed. This clinical decision must factor in the urgency of surgery, the rate that hypokalemia developed, and the manifestation of clinical signs or symptoms. • Proceeding with surgery may require perioperative replacement; however, replenishment must be done slowly and cautiously. Maximal IV repletion rate in most cases is 10–20 mEq/hour (peripheral IV is suggested as 10 mEq/hour; central line access as 20 mEq/hour). • Small changes in plasma levels may actually represent significant total body deficits.

HYPONATREMIA

Adam Romanovsky, MD Sean M. Bagshaw, MD, MSc, FRCPC

BASICS DESCRIPTION • Hyponatremia describes a serum sodium (Na+) concentration <135 mmol/L (Exact value depends on laboratory assay used.) • In addition to being the most common electrolyte derangement, hyponatremia has been associated with increased morbidity and mortality. EPIDEMIOLOGY Incidence

Hyponatremia is the most commonly encountered electrolyte disorder in hospitalized patients Prevalence

• 1–2% in hospitalized patients • 4.4% of postoperative patients • Nearly 30% of critically ill patients

Morbidity

Hyponatremia is associated with prolonged durations of stay in the intensive care and hospital, and associated with a higher rate of discharge to a long-term care facility. Mortality

• Associated with an increased all-cause mortality in hospitalized patients • It is an independent risk factor for death in cirrhosis, heart failure, and following acute myocardial infarction.

ETIOLOGY/RISK FACTORS

Hypoosmolar Hyponatremia. Describes an increase in plasma water in excess of plasma sodium. • Increased endogenous antidiuretic hormone (ADH) – Hypovolemic Intravascular volume depletion. GI losses (diarrhea, vomiting) Skin losses (burns, sweat) Renal losses (diuretics, cerebral salt wasting, ketonuria, bicarbonaturia) Third spacing into a “nonfunctional” space (edema, tissue trauma) Adrenal insufficiency (may also be euvolemic). Decreased aldosterone results in volume contraction due to renal loss; ADH is released in response. Cortisol insufficiency also

stimulates ADH release. – Hypervolemic Decreased effective circulating volume (heart failure, cirrhosis, nephrotic syndrome). In addition to increases in ADH, arterial underfilling is detected by baroreceptors in the aortic arch, carotid sinus, and afferent renal arterioles that then activate the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS) resulting in avid sodium and water retention. – Euvolemic Syndrome of inappropriate ADH secretion (SIADH). Increased levels of ADH cause water retention (decreased serum osmolality). Reset osmostat. A type of SIADH where ADH release is stimulated by a lower osmolality than would be expected in a normal patient. Seen in pregnancy and chronic malnutrition. Hypothyroidism. Mechanism is not completely understood. Possibly due to reduced cardiac output or SIADH. • Increased exogenous ADH (usually euvolemic) – Desmopressin or vasopressin use – Oxytocin infusion during the induction of labor or postpartum • Appropriately suppressed ADH (usually euvolemic but may be hypervolemic) – Insufficient solute to excrete excess free water. In beer drinker’s potomania, excessive hypotonic fluid intake results in an overwhelmed capacity to excrete free water. – Intake of hypotonic fluids – Polydipsia – Excessive hypotonic IV fluids – Absorption of glycine or sorbitol solutions during hysteroscopy or trans-urethral resection of the prostate (TURP) (may be associated with normal or elevated osmolality) Hyperosmolar hyponatremia. May be referred to as redistributive hyponatremia because water shifts from the intracellular to the extracellular compartment with a resultant dilution of sodium. The total body water and total body sodium are unchanged. • Mannitol. This effect is sometimes harnessed during increased intracranial pressure to decrease cerebral volume. Similarly, for neurosurgical cases, mannitol may be administered prior to opening the dura to decrease brain volume and protrusion. • Hyperglycemia • Maltose (IVIg) • Pseudohyponatremia. The plasma is diluted by excessive proteins or lipids. The total body water and total body sodium are unchanged. – Hyperproteinemia – Hyperlipidemia PHYSIOLOGY/PATHOPHYSIOLOGY

• Antidiuretic hormone (ADH). Excessive exogenous or endogenous ADH prevents the excretion of maximally dilute urine. – ADH results in free water absorption as water moves passively down its concentration gradient from the tubules to the hypertonic medullary interstitium via aquaporin-2

channels in the medullary collecting ducts. – Endogenous ADH release from the posterior pituitary gland is normally stimulated by an increase in serum osmolality thereby maintaining normal serum osmolality between 280 and 300 mOsm/kg. Sodium, along with its anion (mostly chloride or bicarbonate) account for the vast majority of serum osmoles. – ADH release may be enhanced despite a low serum osmolality in the following situations (described above under etiology): Decreased intravascular volume (in an attempt to maintain serum volume) Decreased effective circulating fluid volume SIADH and reset osmostat – Exogenous ADH acts in the same way as endogenous ADH with resultant free water absorption and hyponatremia. – In polydipsia and beer drinker’s potomania, patients excrete maximally dilute urine; however, their excessive intake of hypotonic fluid overwhelms the renal diluting capacity resulting in hyponatremia. • Neurological effects – Hyponatremia increases free water movement into the intracellular space and cellular edema. Because of the fixed space of the cranium, symptoms manifest from increased intracranial volume and can result in herniation and death. When chronic, the cells are able to compensate by moving solutes out and into the extracellular space (water moves extracellularly as well); this decreases the pathological effects.

DIAGNOSIS • The history and physical exam should be focused on searching for the underlying cause, assessing volume status, and determining if the derangement is acute (present <48 hours) or chronic (present >48 hours or if uncertain of time onset) causes • History – Fluid loss from diarrhea, burns, vomiting – Cardiac, renal, and hepatic disorders – Medications (desmopressin, thiazide diuretics, oxytocin, carbamazepine, SSRIs) – IV fluids – Surgical history • Symptoms – Mild and chronic cases are often asymptomatic – Acute or more severe cases may have nausea, malaise, lethargy, headache, or seizures • Signs/physical exam – May have altered mental status or be obtunded – Assessment of intravascular volume status: Jugular venous pressure, capillary refill, edema, dry mucous membranes, hypotension, and tachycardia • Laboratory investigations: Serum osmolality, urine osmolality, urine sodium • Additional studies such as creatinine, urea, liver function panel, cortisol, and TSH can further aid with the diagnosis.

DIFFERENTIAL DIAGNOSIS

• Measurement of serum osmolality and serum glucose will rule out hyperosmolar hyponatremia. – Hyperglycemia: Na+ is decreased by 1.6 mEq/L for every 100 mg that glucose exceeds 100 mg. True [Na+] = [Na+] + [1.6 (glucose−100)/100] • Clinical exam to assess the volume status is important in differentiating between hypervolemic, euvolemic, and hypovolemic hyponatremia. • Patients with intravascular volume depletion and decreased effective circulating fluid volume tend to avidly retain sodium and therefore have a low urine [Na+]. – Urine [Na+] is typically <20 mEq/L – Fractional excretion of sodium (FENa) is a more accurate way to determine sodium excretion. – FENa = ([Na+]urine × Crplasma)/([Na+]plasma × Crurine) × 100; a FENa <1–2% is consistent with avid sodium retention. – An exception is when renal sodium loss leads to volume contraction (e.g., diuretics and cerebral salt wasting). [Na+]urine and FENa are usually >20 mEq/L and >2%, respectively.

In these circumstances, a FEurea <30% suggests avid renal reabsorption – Because of high levels of ADH, urine osmolality will be high (>400 mOsm/L). • Patients with hyponatremia from SIADH or exogenous ADH do not avidly retain sodium. Typically, [Na+]urine is >20 mEq/L and FENa >2%.

– Urine osmolality is inappropriately high (exact value depends on degree of excess ADH secretion/administration). • Polydipsia and beer drinker’s potomania present with maximally dilute urine (<100 mOsm/L). – These patients do not avidly retain sodium. – FENa is typically >2% but [Na+]urine may be low due to high urine volumes.

TREATMENT • Identify and manage acute symptomatic hyponatremia before proceeding with the operation. In addition, when specific causes can be identified they should be treated accordingly: – Intravascular depletion from GI or renal losses, as well as insensible and third spacing, should be repleted. – Congestive heart failure: Volume overload should be treated with diuresis and/or optimization of cardiac function (may require inotropic agents). Sodium and water restriction are imperative. – Volume overload states such as cirrhosis should be managed with water and sodium restriction, diuresis, and treatment of underlying disorder. – SIADH is managed with water restriction and management of the underlying disorder (see SIADH chapter). Other possible therapies include demeclocycline or vasopressin antagonists.

– Polydipsia is managed with water restriction • Sodium correction. Prevent excessive rises in [Na+] in patients with documented chronic hyponatremia (>48 hours). – Maximum rate of change <0.5 mmol/L/hour (<10 mmol/L in 24 hours, <18 mmol/L in 48 hours) – Rapid increases in [Na+] in chronic hyponatremia can lead to osmotic demyelination. • Avoid intraoperative exacerbation of hyponatremia. Worsening hyponatremia may lead to cerebral edema, seizures, and possibly death.

FOLLOW-UP • Repeat serum electrolytes • Consider medicine or nephrology consultation

REFERENCES

1. Bagshaw SM, Townsend DR, Mcdermid RC. Disorders of sodium and water balance in hospitalized patients. Can J Anesth. 2009;56:151–167. 2. Wald R, Jaber BL, Price LL, et al. Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med. 2010;170(3):294–302. 3. Sterns R, Cappuccio J, Silver S, et al. Neurologic sequelae after treatment of severe hyponatremia: A multicenter perspective. J Am Soc Nephrol. 1994;4:1522–1530. 4. Adrogué, HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581–1589. See Also (Topic, Algorithm, Electronic Media Element)

• TURP syndrome • Hypernatremia • Urine osmolality • Plasma osmolarity • Hypothyroidism • Syndrome of inappropriate antidiuretic hormone (SIADH)

CODES ICD9 276.1 Hyposmolality and/or hyponatremia ICD10 E87.1 Hypo-osmolality and hyponatremia

CLINICAL PEARLS

• Hyponatremia should not be ignored. • To proceed or delay? Elective surgeries should be delayed for a [Na+] <130 mmol/L in

order to complete a full workup and begin treatment. Proceeding with urgent or emergent surgeries must be done with caution while weighing the risk–benefit ratio of delay. • Perioperatively, worsening of hyponatremia or a rapid rise of serum [Na+] in chronic hyponatremia should be avoided.

HYPOTHERMIA N. Matthew Decker, BS

BASICS DESCRIPTION

• Hypothermia refers to a subnormal core temperature (<37°C) and can be divided into three subcategories: – Mild hypothermia: 32–35°C – Medium hypothermia: 28–32°C – Severe hypothermia: <28°C • Perioperative hypothermia occurs in three phases: – An initial decrease in core temperature of 1–1.5°C in the first hour of anesthesia – Slower linear decrease in heat due to heat loss outpacing metabolic heat production – After 3–5 hours of anesthesia, a thermal plateau of core temperature EPIDEMIOLOGY Incidence

• Nearly all patients undergoing general anesthesia become mildly hypothermic (1–3°C reduction in core body temperature). – Varies between centers; reported to be as high as 70% (1)[B] • Hypothermia is often undetected during spinal and epidural anesthesia due to reduced monitoring of core temperature and inability of patients to feel cold. Morbidity

• Mild hypothermia has been shown to increase blood loss by ∼16% and relative risk for transfusion by 22% (2)[A]. • Mild hypothermia is associated with – Myocardial ischemia (can be therapeutic in cardiopulmonary bypass), arrhythmias. – Surgical wound infection – Prolonged recovery from anesthesia

Mortality

No specific data available; cause of death is difficult to differentiate between hypothermia related complications and preexisting comorbidities. ETIOLOGY/RISK FACTORS

• Body morphology. Insulating properties of fat reduce core-to-peripheral temperature gradient. Risk of hypothermia is inversely proportional to patient body fat percentage. • Age extremes – Infants and young children have a high surface area to mass ratio, allowing intraoperative heat loss to easily exceed metabolic heat production.

– Geriatric patients have a lower metabolic rate, thus produce less metabolic heat. • Size of incision • Severe trauma (including burns) • Chronic illness decreases metabolic heat production (e.g., cardiovascular disease).

PHYSIOLOGY/PATHOPHYSIOLOGY

• All general anesthetics cause a loss in core body temperature, mostly from reducing thermoregulatory controls and promoting vasodilation. • Heat loss can result from: – Radiation. Describes the transfer of heat from one surface to another by emission of photons. Heat from the patient radiates into the cool operating room air and accounts for ~90% of heat loss. – Convection. Describes the carrying of heat from the core to the periphery. Second largest contributor to heat loss (after radiation) Dependent on peripheral blood flow and core-to-peripheral temperature difference – Conduction. Adjacent tissue-to-tissue transfer of heat. Slow Dependent on tissue characteristics (insulation properties of tissue, diffusion coefficient) and differences in surface temperatures. – Evaporation. Derived from heat of vaporization of water (0.58 kcal/g) Respiratory evaporative losses are small, usually <10% of basal metabolic rate. Substantial heat loss occurs from evaporation through the surgical incision. Skin-prep (especially alcohol-based) solutions contribute to evaporation heat loss (–0.2 to –0.7°C/m2 depending on solution). – Cold intravenous fluids. The body warms cold fluids via conduction from blood and tissues. IV fluid at room temperature decreases mean body temperature ∼0.25°C per liter. – Irrigation. Irrigation fluid can reduce core body temperature by carrying heat way from core organs (via conduction). • Neurologic effects – Cerebral metabolic rate of oxygen (CMRO2) decreases by 6–7% for every 1° decrease in

temperature. – Delayed awakening from anesthesia • Cardiac effects of hypothermia – Heart rate and cardiac output gradually decrease – Hypotension (particularly in severe hypothermia) – Atrial and ventricular arrhythmias increase. Atrial fibrillation can occur secondary to atrial distention. Ventricular fibrillation is an immediate hazard at core temperatures <28°C. – Prolonged asystole (most commonly occurs at core temperatures below 32°C) – J-waves (Osborn waves), positive deflections at the end of the QRS complex, appear on ECG (typically below 30°C). Clinically insignificant and disappear on rewarming. – During cardiopulmonary bypass, hypothermia is utilized to decrease the myocardial metabolic rate (decreases oxygen consumption during periods of decreased oxygen supply). The perfusion pump is utilized to rapidly cool (and rewarm) the patient; it dwarfs

all other sources of heat transfer (e.g., radiation, convection). Afterdrop is a term used to describe a rapid decrease in core temperature that can occur after discontinuation of bypass. It is caused by a large core-to-peripheral temperature gradient and from insufficient rewarming of peripheral tissues. • Pulmonary effects of hypothermia – Pulmonary vascular resistance (PVR) increases. – Significant respiratory depression can occur with severe hypothermia. – Reduced cough reflex and cold-induced bronchorrhea can lead to aspiration and difficulty clearing secretions. • Hepatic effects of hypothermia – Enzyme activity (e.g., conjugation, detoxification) can decrease with a resultant decrease in drug metabolism. – Decreased synthesis of coagulation factors (in addition factors are also sensitive to decreases in temperature). • Hematologic effects of hypothermia – Leukocyte and platelet counts commonly decrease secondary to splenic, hepatic, and intravascular sequestration; this effect reverses with rewarming – Hematocrit levels can increase secondary to volume contraction that results from osmotic diuresis. Consequently, viscosity increases when temperatures drop below 27°C • Metabolic effects – Basal metabolic rate decreases 5–7% per 1°C; at 28°C it is decreased by 50%. – Renal function decreases; a “cold diuresis" occurs secondary to depressed oxidative tubular activity resulting in reduced sodium and water reabsorption. – Insulin release as well as glucose uptake into cells are impaired, resulting in hyperglycemia. This effect is reversed with rewarming. • Therapeutic hypothermia – Indicated for neuroprotection in procedures likely to cause cerebral ischemia (e.g., cardiopulmonary bypass, neurosurgery). Outcome studies have demonstrated increased cerebral performance scores and greater survival after discharge, with no significant difference in adverse events between hypo- and normothermic groups. – Evidence indicates beneficial effect to inducing mild hypothermia within hours of restoring circulation following cardiac arrest (3)[A]. – No significant benefit has been shown from the use of mild hypothermia in the treatment of traumatic head injury (4)[A], stroke (5)[A], or in coronary artery bypass surgery (6) [A].

PREVENTATIVE MEASURES

• Preoperative (on ward, before premedication) – Keep patient comfortably warm. Actively warm patient if hypothermic. • Prior to induction – Measure oral temperature, ask about thermal comfort level. – Prewarm all patients for 20 minutes (forced air) to reduce the core-to-periphery temperature gradient. – Limit skin exposure. – When possible, start anesthesia only when patient is normothermic.

DIAGNOSIS • Oral measurements are adequate but typically 0.2–0.3°C below actual core temperature. • Core temperature measurements through a Foley catheter can be inaccurate in cases of high urine output. • Core temperature <35°C. – Gold standard is pulmonary artery measurement. – Nasopharyngeal, urinary bladder (via Foley catheter), and esophageal measurements are adequate, less invasive alternatives. – Rectal temperature is acceptable in pediatrics, but measurements lag behind core temperature readings in adults (1)[B].

TREATMENT • There is currently no evidence-based gold standard for treating accidental hypothermia. Intraoperative measures may include – Measure patient temperature continuously – Limit skin exposure. A single layer of cutaneous insulation (cotton blanket) can reduce heat loss by 30% (1)[B]. – Active warming with a forced-air warming device can decrease heat loss from radiation as well as rewarm the patient. Its use may not be feasible in trauma cases or where the skin needs to be exposed. – Warm intravenous fluids when administered at a rate >1 L/hour – Warm irrigation fluids – Operating room temperature ≥21°C In anesthetized neonates, risk of hypothermia was roughly doubled when OR temperature <23°C.

FOLLOW-UP • Measure patient oral temperature in PACU every 15 minutes. • Continue active warming until the patient is normothermic. • Shivering. Can result in increased myocardial oxygen consumption up to 200–300%. For shivering, meperidine 25 mg IV or clonidine 75 μg IV may be utilized (1)[B].

CLOSED CLAIMS DATA

• 54/3,000 total anesthesia claims secondary to burns. • 64% of burns were due to IV fluid bags or bottles warmed in an oven prior to applying to patient’s skin. • 0 claims attributed to injuries due to forced-air warming (7).

REFERENCES

1. Torossian A. Thermal management during anaesthesia and thermoregulation standards for the prevention of inadvertent perioperative hypothermia. Best Pract Res Clin Anaesthesiol.

2008;22(3):659–668. 2. Rajagopalan S, Mascha E, Na J, et al. The effects of mild perioperative hypothermia on blood loss and transfusion requirement. Anesthesiology. 2008;108:71–77. 3. Arrich J, Holzer M, Herkner H, et al. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database Syst Rev. 2010;8. 4. ydenham E, Roberts I, Alderson P. Hypothermia for traumatic head injury. Cochrane Database Syst Rev. 2009;4:CD001048.

5. en Hertog HM, van der Worp HB, Tseng MC, et al. Cooling therapy for acute stroke. Cochrane Database Syst Rev. 2009;1:CD001247. 6. ees K, Beranek-Stanley M, Burke M, et al. Hypothermia to reduce neurological damage following coronary artery bypass surgery. Cochrane Database Syst Rev. 2009;1.

7. Cheney FW, Posner KL, Caplan RA, et al. Burns from warming devices in anesthesia. Anesthesiology. 1994;80:806–810.

ADDITIONAL READING

• Kelly FE, Nolan JP. The effects of mild induced hypothermia on the myocardium: A systematic review. Anaesthesia. 2010;65:505–515. • Rueler JB. Hypothermia: Pathophysiology, clinical settings, and management. Ann Intern Med. 1978;89:519–527. • Sessler DI. Mild perioperative hypothermia. N Engl J Med. 1997;336(24):1730–1737. • Sessler DI. Perioperative heat balance. Anesthesiology. 2000;92:578–596.

See Also (Topic, Algorithm, Electronic Media Element) • Circulatory arrest • Cardiopulmonary bypass

CODES ICD9 991.6 Hypothermia ICD10 • T88.51XA Hypothermia following anesthesia, initial encounter • T88.51XD Hypothermia following anesthesia, subsequent encounter • T88.51XS Hypothermia following anesthesia, sequela

CLINICAL PEARLS

• The majority of heat loss in patients is due to a core-to-peripheral temperature gradient and cutaneous radiation. • Nearly all patients under general anesthesia undergo mild hypothermia. Those under neuraxial anesthesia (spinal, epidural) are also at risk

• Mild hypothermia is associated with increased bleeding, greater susceptibility to infection, and morbid cardiac events. • Deep hypothermic circulatory arrest (DHCA) may be used concurrently with cardiopulmonary bypass in complex cardiac and proximal thoracic aortic procedures. DHCA is thought to increase ischemic tolerance and protect against injury to the CNS, viscera, and kidneys.

HYPOTHYROIDISM Joe C. Hong, MD

BASICS DESCRIPTION

Hypothyroidism is a clinical state resulting from decreased circulating levels of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) or from peripheral hormone resistance. EPIDEMIOLOGY Incidence

• ∼4:1,000 women per year. • ∼0.6:1,000 men per year.

Prevalence

• 1.9% of the female US population. • 0.1% of the male US population. • 6.9%–7.3% of patients age 55 or over. • Women are 10 times more likely to be hypothyroid compared to men (1).

Morbidity

• Patients with hypothyroidism are at increased risk for atherosclerotic heart disease due to increased incidence of hypercholesterolemia. • Increased incidence of dementia and depression

Mortality

• Severe hypothyroidism may lead to coma and death if untreated. • Increased incidence of suicide

ETIOLOGY/RISK FACTORS

• Female sex • Elderly • Positive family history • History of autoimmune disorders • History of treatment with radioactive iodine or antithyroid medications such as propylthiouracil (PTU) or methimazole • History of radiation to the neck • History of thyroid surgery

PATHOPHYSIOLOGY

• Thyroid hormone functions in several capacities, including normal heart, liver, kidney, and skeletal muscle metabolism, as well as cell differentiation and growth.

• T4 and T3 are produced by follicular cells in the thyroid gland in a classic negative feedback system. Thyroid-releasing hormone (TRH; from the hypothalamus) stimulates the release of thyroid-stimulating hormone (TSH; from the anterior pituitary), which in turn stimulates T3 and T4 release (from the thyroid gland). T3 and T4 inhibit synthesis and release of TRH and TSH, via a feedback loop. Additionally, high levels of iodide ion can inhibit T4 synthesis and release. • Hormone synthesis involves iodide uptake into the gland, iodination of thyroglobulin, coupling of iodotyrosines to form T4 and T3. T4 and T3 are released from the thyroid gland into the bloodstream (20:1 ratio). • When T4 enters target cells, it is converted to T3 (more potent). Both T4 and T3 bind to thyroid receptor proteins within the cell nucleus and activate DNA transcription and increase the rate of RNA synthesis, which ultimately affects protein synthesis. • Hypothyroidism manifests as the lack of physiologic activities of T3 and T4. Primary hypothyroidism (95% of cases) is defined by the inability of the thyroid gland to produce thyroid hormones, while secondary hypothyroidism is defined as a functional thyroid gland that is deprived of TSH (2). ANESTHETIC GOALS/GUIDING PRINCIPLES

• Determine the severity and tailor an anesthetic plan to the concomitant organ dysfunction. • Mild or well controlled hypothyroidism likely poses no increased surgical risk.

PREOPERATIVE ASSESSMENT SYMPTOMS

• General: Lethargy, decreased vigor, cold intolerance, diminished food intake, and weight gain. • Neurologic: Slow thinking. • Integument: Dry skin, thickened hair, hair loss, broken nails. • Gastrointestinal (GI): Constipation. • Gynecologic: Menorrhagia, diminished libido.

History

• Focus on the multiple systems affected by the lack of physiologic activity of T3 and T4. • Symptoms are insidious in onset and easily overlooked despite multisystem involvement. • In patients with a history of Hashimoto’s thyroiditis, a careful review of associated autoimmune diseases such as lupus erythematosus, rheumatoid arthritis, primary adrenal insufficiency, and Sjögren’s syndrome is necessary.

Signs/Physical Exam

• Neurologic: Slow speech, mental slowing, depression. • HEENT: Round puffy face, periorbital edema, hoarseness. • Integument: Cold/thick/dry/scaling skin, dry/coarse/brittle hair, dry and longitudinally ridged nails. • Cardiovascular: Bradycardia, decreased stroke volume, narrow pulse pressure, cardiac enlargement, pericardial effusion.

• GI: Ascites. • Extremities: Ankle edema. • In severe hypothyroidism or myxedema, there can be impaired mentation, coma, enlarged tongue, decreased upper airway tissue tone, hypoventilation, CHF, hypothermia, and hyponatremia secondary to SIADH. MEDICATIONS

• Replacement therapy is typically with synthetic T4 (levothyroxine) which may take up to 2 weeks before symptomatic improvement is seen. • Synthetic T3, which is the biologically active form of thyroid hormone, can be used to attain a more acute response. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Increased TSH for primary hypothyroidism; decreased TSH for secondary hypothyroidism. • Decreased thyroid hormones T3 and T4. • Decreased radioiodine uptake by the thyroid gland. • Macrocytic anemia. • Elevated serum cholesterol and CK level. • Hypoglycemia, hyponatremia. • Low voltage EKG.

CONCOMITANT ORGAN DYSFUNCTION

• Degree of organ dysfunction is concomitant with the severity of hypothyroidism. • Cardiac involvement includes pericardial effusion, QT prolongation, T-wave inversion, and CHF; also, decreased cardiac output (stroke volume and heart rate), pulse pressure, and blood volume hinders the heart’s ability to respond to circulatory stress. • Pulmonary involvement includes decreased respiratory drive in response to hypoxemia and hypercarbia, decreased maximal breathing capacity, and decreased diffusion capacity for carbon monoxide. • CNS involvement includes increased sensitivity to sedative medications and decreased level of consciousness progressing to coma. CIRCUMSTANCES TO DELAY/CONDITIONS

• Patients with signs and symptoms of severe hypothyroidism or myxedema should have elective surgery postponed until after adequate replacement therapy. • Patients with severe hypothyroidism or myxedema requiring emergent surgery require immediate hormone replacement with T3, stress dose steroids, and intensive monitoring of their response to therapy. • In patients with coronary artery disease, care must be taken during thyroid replacement therapy. Several studies have shown that replacement therapy may exacerbate angina and even induce myocardial infarction. • Most experts believe mild hypothyroidism poses no increased surgical risk (3).

TREATMENT PREOPERATIVE PREPARATION Premedications

• Carefully titrate sedatives and analgesics because hypothyroid patients may be more sensitive to these medications. • Aspiration prophylaxis should be considered because severe hypothyroidism or myxedema may have a significant delay in gastric emptying. INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia is indicated for thyroidectomy. • Anesthesia technique for nonthyroid surgery should be dictated by the type of surgery, planned position, as well as surgeon/anaesthetist preference. • Patients with severe hypothyroidism or myxedema should be intubated and have their ventilation controlled due to decreased respiratory response to hypoxemia and hypercarbia. Monitors

• Standard ASA monitors. • Invasive monitoring as dictated by the type of surgery, patient comorbidities, and severity of hypothyroidism. • Patients with severe hypothyroidism or myxedema are particularly susceptible to CHF. Pulmonary artery catheter, peripheral arterial catheter, and transesophageal echocardiography may be helpful to guide ionotropic support and fluid management. • EMG endotracheal tube per surgeon request for thyroid surgery.

Induction/Airway Management

• Large goiter can cause tracheal deviation, compression, and tracheomalacia. In addition, the frequently associated findings of obesity, large tongue, and decreased upper airway tone among hypothyroid patients can make airway management difficult. Awake fiberoptic intubation should be considered, if there is a high suspicion for airway compromise. • Ketamine may be the induction agent of choice in patients with severe hypothyroidism or myxedema due to its inotropism and ability to maintain sympathetic tone. • Rapid or modified rapid sequence induction may be warranted in patients with significant delay in gastric emptying. Maintenance

• Mixed technique of a volatile agent, nitrous oxide, and short-acting opioid may be the technique of choice. The presence of nitrous oxide and opioid will allow for a lower concentration of the volatile agent, resulting in less cardiac depression and vasodilation. • Controlled ventilation is necessary in patients with severe hypothyroidism or myxedema due to impaired ventilatory response to hypercarbia and hypoxemia. • Minimum alveolar concentration is unchanged in patients with hypothyroidism (4). • Warming blanket and warm IV fluids should be used to minimize risk of hypothermia.

Extubation/Emergence

• For thyroidectomies, coughing/bucking on emergence should be minimized to decrease the likelihood of neck hematoma formation. Preintubation tracheal lidocaine can provide airway analgesia. • Because of increased sensitivity to sedatives and analgesics, the use of non-narcotic analgesics may help prevent delayed emergence. • Complications: – Delayed emergence due to increased sensitivity to sedatives and analgesics. – Hypothermia. – Postoperative dependence on mechanical ventilation. – Thyroidectomy: Airway compromise such as hematoma, airway edema, tracheomalacia, and bilateral recurrent laryngeal nerve injury. Massive bleeding and stroke may occur when injury to the nearby carotid artery occurs. Carotid sinus irritation may lead to hemodynamic fluctuations and bradyarrhythmias. Respiratory compromise from an occult pneumothorax may result from lower neck surgical dissection.

POSTOPERATIVE CARE BED ACUITY

Patients with severe hypothyroidism or myxedema should be monitored in the ICU postoperatively. COMPLICATIONS

For thyroid surgery, postoperative respiratory distress may be the result of a neck hematoma or hypocalcemia causing laryngospasm and decreased upper airway tone. The latter may be difficult to differentiate in the myxedematous patient that has decreased upper airway tone.

REFERENCES

1. Singer PA, et al.Treatment guidelines for patients with hyperthyroidism and hypothyroidism. Standards of care committee, American thyroidassociation. JAMA.1995;273:808. 2. anderpump MP, et al. The epidemiology of thyroid disorders in the community: A twentyyear follow-up of the Whickham Survey. Clin Endocrinol. 1995;43:55. 3. arling PA. Thyroid disease. Br J Anaesth. 2000;85:15. 4. einberg AD, et al. Outcome of anesthesia and surgery in hypothyroid patients. Arch Intern Med. 1983;143:893.

ADDITIONAL READING

• Graham GW, et al. Perioperative management of selected endocrine disorders. Int Anesthesiol Clin. 2000;38:31. • Kohl BA, Schwartz S. How to manage perioperative endocrine insufficiency. Anesthesiol Clin. 2010;28:139.

See Also (Topic, Algorithm, Electronic Media Element) • Thyroidectomy • Hyperthyroidism • Recurrent laryngeal nerve

CODES ICD9

244.9 Unspecified acquired hypothyroidism ICD10

E03.9 Hypothyroidism, unspecified

CLINICAL PEARLS

• The overriding goal of management is determining the severity of the hypothyroidism and designing an anesthetic plan tailored to the concomitant organ dysfunction. • In patients with history of Hashimoto’s thyroiditis, a careful review of associated autoimmune diseases is necessary. • Most experts believe mild hypothyroidism poses no increased surgical risk and patients may be able to proceed for surgery. • Patients with severe hypothyroidism or myxedema must be medically optimized prior to surgery. Replacement therapy with T4 or more acutely with T3 should be undertaken with monitoring of symptomatic improvement. • Careful airway management and possible awake fiberoptic intubation may be indicated in patients with large goiter, large tongue, and/or decreased airway tone. • Severely hypothyroid and myxedematous patients should have appropriate invasive monitoring, induction with ketamine, and airway intubation with controlled ventilation. Careful titration of short-acting opioid analgesics or the use of nonopioid analgesics may help in minimizing the risk of delayed emergence.

HYPOXIA, INTRAOPERATIVELY Suzanne Strom, MD

BASICS DESCRIPTION

Intraoperative hypoxia is defined as arterial oxygen tension (PaO2) <60 mm Hg, which

correlates to a blood oxygen saturation (SpO2) <90%. EPIDEMIOLOGY Incidence

Transient intraoperative hypoxia has been shown to occur in 7% of patients who receive an anesthetic for surgery. Prevalence

• Hypoxia can occur during all stages of the anesthetic, particularly during induction and emergence. • It occurs most frequently in patients with American Society of Anesthesiology (ASA) physical status classification III and IV. Morbidity

Hypoxic brain injury, myocardial ischemia, stroke, renal injury ETIOLOGY/RISK FACTORS

• Decreased fraction of inspired oxygen (FiO2) results from a failure to provide adequate inspired O2. It can result from

– Pipeline O2 supply failure, empty tank, hypoxic gas mixture

– Higher altitude • Inadequate alveolar ventilation or alveolar hypoventilation. The alveolar gas equation is as follows: FA = [(Pbarometric – PH20)(FiO2)] –(PaCO2/0.8); increases in carbon dioxide in the alveoli will decrease the FAO2 and, hence, PaO2.

– CNS depression. Respiratory depression from drugs, structural, or ischemic lesions – Circuit or machine disconnection – Obstruction. Upper airway, mucous plug, endotracheal tube (ETT) kink, herniated ETT cuff – Inadequate ventilator settings/parameters • Venous admixture. Under normal conditions, there is a fixed physiologic shunt (∼5%) from pleurohilar veins, bronchial veins, and Thebesian circulation. • V/Q mismatch – Dead space: Pulmonary embolism, profound hypotension, cardiac arrest

– Shunt: Bronchospasm, asthma, pneumonia, endobronchial intubation, pulmonary edema, aspiration, inhibition of hypoxic pulmonary vasoconstriction (HPV), pneumothorax, pleural effusion, hemothorax, acute lung injury (ALI), acute respiratory distress syndrome (ARDS) • Right-to-left anatomic shunts – Atrial septal defects – Ventricular septal defects • Diffusion defects. Diffusion capacity depends on the thickness of the alveolar wall, the area available for gas exchange, and the partial pressure difference of gas between the two sides. – Thickened wall. Pulmonary fibrosis (chronic) or pulmonary edema (acute) – Decreased equilibration time secondary to tachycardia • Excessive metabolic O2 demand such as hyperthermia, hyperthyroidism, shivering, and malignant hyperthermia (result in a decreased mixed venous oxygen saturation). • Impaired tissue oxygen delivery/perfusion – Myocardial infarction – Congestive heart failure – Shock – Arrhythmias – Cardiac tamponade – Sepsis – Arteriovenous malformation

PHYSIOLOGY/PATHOPHYSIOLOGY

• Aerobic metabolism. Each molecule of glucose can generate 36 ATP under normal cellular metabolism and oxidative phosphorylation. – C6H12O6 + 6O2 → 6CO2 + 6H2O + Energy

– The energy created is stored in the third phosphate bond on adenosine triphosphate (ATP). ATP is utilized for muscle contraction, ion pumps, cellular secretion, and protein synthesis: Energy + ADP + Phosphate → ATP – ATP cannot be stored and must be continually formed requiring a constant supply of substrates and O2.

• Anaerobic metabolism. When O2 is not available, anaerobic metabolism occurs in order to manufacture ATP; however, it is inefficient (one glucose molecule yields 2 ATP) and produces lactic acid. Progressive lactic acidosis impairs enzymatic function and ion concentration gradients. • Hypoxia is sensed in the carotid bodies (at the bifurcation of the common carotid arteries) and the aortic bodies (surrounding the aortic arch). These peripheral sensors interact with central respiratory centers via the glossopharyngeal nerves to produce reflex increases in alveolar ventilation. Hypoxia receptor activity does not appreciably increase until the PaO2 decreases below 50 mm Hg, at which point the SpO2 is 80%.

• Compensatory mechanisms. When there is an imbalance of O2 supply to demand, the body

mobilizes its compensatory mechanisms to ensure adequate availability (e.g., increased O2

extraction and cardiac output). • Signs of hypoxia. Early signs are the result of sympathetic system activation and include tachycardia, hypertension, and an increased cardiac output. Late signs include myocardial dysrhythmias, bradycardia, hypotension, and cardiac arrest.

PREVENTATIVE MEASURES

• Deliver adequate supplemental FiO2

• Carefully monitor for signs of hypoventilation

DIAGNOSIS • Verify all low SpO2 measurements.

– Ensure that the SpO2 rate correlates with the EKG tracing

– Verify accurate waveform – Move pulse oximetry probe to different fingers, or an earlobe, nostril, or nasal ala. • Check in-line FiO2 measurements.

• Assess for adequate ventilation – If the patients is not intubated, listen for stridor, snoring, lack of air movement. – If intubated, hand ventilate to assess pulmonary compliance and expand collapsed lung segments. Increased compliance: Consider cuff leak or deflation, supraglottic cuff, circuit leak Decreased compliance: Consider bronchospasm, pneumothorax, mainstem intubation, pulmonary edema; biting, secretions, or kinking of the ETT – Auscultate the lungs to assess for Bilateral breath sounds; rules out mainstem intubation, pneumothorax. Wheezing; rules out bronchospasm, aspiration, pulmonary embolism Crackles or rales; rules out pulmonary edema – Check end-tidal CO2 (EtCO2) to verify intubation and evaluate capnograph pattern for

abnormalities such as obstruction. • Portable chest x-ray should be obtained to ascertain atelectasis, infiltrates, or pneumothorax. • Measure the arterial blood gas to evaluate the PaO2. The SpO2 is a non-invasive monitor that may not accurately reflect the PaO2 in the setting of: Hypothermia, poor circulation,

electrocautery, motion, ambient lighting, carbon monoxide poisoning, methylene blue administration, and cyanide poisoning. Additionally, PaO2 values can be utilized to calculate the Alveolar to arterial gradient/ratio.

DIFFERENTIAL DIAGNOSIS

• Evaluating the Alveolar to arterial (A-a) gradient may help determine the cause. Alternatively the a/A ratio can be utilized when increased FiO2 is being implemented.

• Oxygen administration may help differentiate between hypoventilation and V/Q mismatch. In patients with: – Low FiO2, hypoventilation, and V/Q mismatching, increasing the FiO2 will increase the

oxygen saturation. – Large shunts (>25% of total cardiac output), the blood flow that returns from unventilated alveoli or right-to-left anatomic shunts will be unchanged; it is not exposed to the increased oxygen fraction.

TREATMENT • Increase delivered FiO2 to 100% while evaluating reversible causes

• Atelectasis is the most common cause; recruitment maneuvers can be very effective: – Increase tidal volumes (Vt) to 10–12 mL/kg – Add positive end-expiratory pressure (PEEP) – Recruitment maneuvers – Alternatively, some patients with hypoxia have ALI or ARDS and management is based on a lung protective ventilation strategy (LPVS) that minimize additional ventilatorassociated lung injury using lower Vt. • Secretions: Suction the ETT, consider bronchoscopy • Biting: Place a bite block, deepen anesthetic, administer neuromuscular blocking drugs. • Bronchospasm: Administer aerosolized bronchodilators, deepen the anesthetic with volatile agents or propofol • Hypoventilation: Adjust minute ventilation. In patients that are not intubated, alleviate possible upper airway obstruction (chin life, jaw thrust, oronasopharyngeal airway insertion, suction oropharynx, apply positive pressure ventilation with a mask, or consider LMA/ETT insertion). • Pneumothorax: Needle decompression if hemodynamically unstable; if time permits, a chest tube should be inserted • Diffusion problems: If pulmonary edema, increase the surface area for diffusion by increasing the transalveolar pressure (administration of continuous positive airway pressure [CPAP] if not intubated, PEEP if intubated). • Machine issue: If suspected, immediately convert to an Ambu bag while searching for the cause (disconnect, internal issue); do not let the patient deteriorate while searching for the cause • Maintain adequate cardiac output and hemoglobin levels • If hypoxia does not resolve with appropriate interventions, terminate surgery as soon as possible

FOLLOW-UP CLOSED CLAIMS DATA

• In the 1986 Closed Claims review, adverse outcomes associated with respiratory events constitute the single largest class of injury (522 of 1,541 cases; 34%). Death or brain damage occurred in 85% of cases. Most outcomes (72%) were considered preventable with better monitoring. Inadequate ventilation (196; 38%) was one of the three mechanisms of injury and accounted for 75% of the adverse respiratory events.

• In the 2000 review, which looked at the period of time after widespread introduction of pulse oximetry and EtCO2 monitoring, the adverse outcomes associated with respiratory events decreased significantly.

REFERENCES

1. Blum JM, Fetterman DM, Park PK, et al. A description of intraoperative ventilator management and ventilation strategies in hypoxic patients. Anesth Anal. 2010;110(6):1616–1622. 2. are G, Kavanagh B. Hypoxemia during surgery: Learning from history, science, and current practice. Can J Anesth/J Can Anesth. 2010;57:877–881. 3. Pedersen T, Moller AM, Hoyannisyan K. Pulse oximetry for perioperative monitoring. Cochrane Database Syst Rev. 2009;4:CD002013. • Ehrenfeld JM, Funk LM, Van Schalkwyk J, et al. The incidence of hypoxemia during surgery: Evidence from two institutions. Can J Anesth. 2010;57. See Also (Topic, Algorithm, Electronic Media Element)

• Hypoxia, postoperatively • Carotid body • Dead space • Anaerobic metabolism • Alveolar-arterial gradient and ratio • Pneumothorax

CODES ICD9 • 799.02 Hypoxemia • 998.9 Unspecified complication of procedure, not elsewhere classified ICD10 • R09.02 Hypoxemia • T81.89XA Oth complications of procedures, NEC, init

CLINICAL PEARLS

• Always assume a low SpO2 is accurate until proven otherwise.

• Atelectasis is the most common cause of intraoperative hypoxia. Recruitment maneuvers may need to be done regularly in intubated patients with decreased functional residual capacity (FRC) such as obesity, pregnancy, laparoscopic procedures, and Trendelenburg position. Similarly, recruitment maneuvers might be necessary in those with increased closing capacity such as the elderly. • Hypoxia should always be at the top of a differential diagnosis for abnormal cardiovascular vital signs such as hypertension, tachycardia, and arrhythmia, as well as nausea and altered

mental status.

HYSTERECTOMY Natesan Manimekalai, MD

BASICS DESCRIPTION General

• Hysterectomy is the surgical removal of the uterus and is the second most frequently performed surgical operation in the US after Caesarean section. • Emergent hysterectomy is performed in the immediate postpartum period for uncontrollable hemorrhage from rupture, placenta accreta, and uterine atony. • Elective hysterectomy is performed for several indications: – Uterine fibroids (30%) – Dysfunctional uterine bleeding (20%) – Endometriosis and adenomyosis (20%) – Genital prolapse (15%) – Pelvic inflammatory disease – Endometrial hyperplasia – Cervical intraepithelial neoplasia, invasive uterine cancer, and ovarian cancers • Types of hysterectomy – Total hysterectomy. Surgical removal of the uterus including the cervix. This is the most common type. – Partial or supracervical hysterectomy. Upper portion of the uterus is removed leaving the cervix intact. – Total hysterectomy with bilateral salpingo-oophorectomy. In addition to the entire uterus with the cervix, ovaries and fallopian tubes are also removed. – Radical hysterectomy. Removal of the cervix, the uterus, the upper portion of the vagina, and supporting tissues with pelvic lymph nodes. Usually done for cervical or endometrial cancer. • Surgical approaches (1) – Abdominal hysterectomies Indications: Multiple fibroids and/or the presence of abdominal adhesions from previous abdominal surgeries May have increased postoperative pain and impaired wound healing because of the abdominal scar – Vaginal hysterectomy Indications: Uterine prolapse, dysfunctional uterine bleeding, and/or obese patients in whom healing of an abdominal wound may be compromised. – Advantages over abdominal hysterectomy: Shorter hospital stay, lower cost, and faster recovery. Reduction in overall postoperative morbidity and period of convalescence. – Laparoscopic-assisted vaginal hysterectomy (LAVH): Removal of the uterus through the

vaginal approach, with assistance from laparoscopic instruments inserted through small incisions in the abdomen. Advantages over abdominal hysterectomy: Decreased postoperative pain, faster postoperative healing, and shorter hospital stay Disadvantage of LAVH: Longer duration of surgery and increased risk of major complications – Total laparoscopic hysterectomy. Complete removal of the uterus by laparoscopy. Accomplished with a morcellator, an instrument that cuts the uterus into small pieces and can be removed from the abdominal cavity via the laparoscopic ports. – Robotic–Da Vinci hysterectomy. Removal of the uterus using the laparoscopic instruments remotely operated by the surgeon.

Position

• Abdominal hysterectomy: Supine • Total laparoscopic and robotic hysterectomy: Supine with steep Trendelenburg • Vaginal hysterectomy and LAVH: Lithotomy

Incision

• Abdominal: Vertical or transverse (Pfannenstiel) in the lower abdomen • Vaginal: Small vaginal incision • LAVH: Abdominal small incisions for trochars; small vaginal incision • Total laparoscopic and robotic hysterectomy: Small abdominal incisions for trochars only

Approximate Time

• Abdominal hysterectomy: ∼1–3 hours • Vaginal hysterectomy: ∼1–3 hours • Laparoscopic hysterectomy, LAVH, and robotic hysterectomy: ∼2–6 hours

EBL Expected

• Elective hysterectomy: 200–600 mL • Peripartum hysterectomy: 2,000–4,000 mL. Increased blood loss can be due to the larger size of the uterus, more friable tissue, and dilated blood vessels in the uterus and pelvis (2).

Hospital Stay

• Abdominal hysterectomy: 3–5 days • Vaginal, LAVH, laparoscopic, and robotic: 2–3 days

Special Equipment for Surgery • Laparoscopic equipment • Morcellator • Robotic equipment

EPIDEMIOLOGY Incidence

• 590,000 performed annually in the US.

– 66% via abdominal approach – 22% via vaginal approach – 12% via laparoscopic approach • Peripartum hysterectomy: 4.1 cases per 10,000 births

Morbidity

• The overall hysterectomy-related morbidity rate is 6.1%. • Higher with laparoscopic hysterectomies

Mortality

• For benign cases: 1–6 cases per 10,000 • Cancer related: 29.2 cases per 10,000 • Peripartum: 37.8 cases per 10,000, primarily due to bleeding

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Monitor intraoperative blood loss and maintain hemodynamic stability. • Prevent nerve injuries: – Femoral nerve damage can result from excessive abduction and external rotation of the hip joint. – Peroneal nerve injury can result from suspension of the legs in the stirrups for the lithotomy position. • Plan for good postoperative pain control and early ambulation to prevent DVT and pulmonary embolism (PE).

PREOPERATIVE ASSESSMENT SYMPTOMS

Anemia; pale or weak History

• Indication • Type of hysterectomy • Continuous or profuse bleeding • Assessment of comorbidities like hypertension, diabetes, pulmonary, and renal disease • For cancer, chemotherapy or radiation

Signs/Physical Exam Routine

MEDICATIONS Iron

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies • CBC

• PT/PTT • EKG if indicated • Pregnancy testing for women of childbearing age • Type and screen; if the patient is anemic, crossmatch packed red blood cells. • Consider chemistry and chest x-ray if comorbidities indicate.

CONCOMITANT ORGAN DYSFUNCTION • Anemia from fibroids • Tumor • Postpartum hemorrhage

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics as appropriate • Fluid bolus if the patient appears dehydrated (NPO status, bowel prep)

Special Concerns for Informed Consent

• Potential for transfusion • Choice of anesthesia (general versus neuraxial with sedation) for vaginal and abdominal hysterectomies. • Epidural for postoperative pain management when abdominal performed

Antibiotics/Common Organisms

Third-generation cephalosporin; skin organisms INTRAOPERATIVE CARE Choice of Anesthesia

• Dependent on the type of hysterectomy, patient’s condition, length of the procedure, and patient’s requests. • General anesthesia is the preferred technique for LAVH, total laparoscopic hysterectomy, Robotic–Da Vinci hysterectomy, and radical abdominal hysterectomy. • Neuraxial. Patients may be hypovolemic from bowel preparation, NPO status, or bleeding. – Spinal anesthesia can provide surgical anesthesia for vaginal and simple abdominal hysterectomies. It provides excellent muscle relaxation. – Epidural catheters are commonly placed for postoperative analgesia in combination with general anesthesia. It can also be used to provide surgical anesthesia for total abdominal and vaginal hysterectomy, and the epidural can be used postoperatively for pain. – Combined spinal epidural technique combines the benefits of both modalities. Monitors

• Standard ASA monitors. • Foley catheters aid with monitoring urinary output and detect injury to the urinary tract

(heme). • Arterial line may be considered based on comorbidities: End-organ damage requiring beatto-beat BPs and frequent blood draws (hemoglobin, glucose). • Central line access and pressures may be considered based on comorbidities or extensive resection.

Induction/Airway Management

• General anesthesia is performed with an endotracheal tube. Induction may unmask hypovolemia from bowel preparation and NPO status. • Spinal anesthesia. Use a small needle, to minimize the incidence of spinal headache. Typically, bupivacaine is utilized with a short (fentanyl) and/or long (morphine) acting opioid.

Maintenance

• An oral gastric tube is placed to decompress the stomach in laparoscopic cases. May be considered for abdominal cases as well to potentially decrease the risk of postoperative nausea and vomiting. • Temperature. Fluid warmers, blanket warmers, and airway humidifiers can be used to prevent hypothermia. • Fluids. Administration is based on NPO status, bowel prep, and blood loss. Ins and outs should be carefully monitored. Abdominal incisions can have increased insensible losses that should be accounted for and repleted as appropriate. • Methylene blue dye. The surgeon may request IV administration to detect urinary tract injury. Normally, it remains intravascularly and is excreted in the urine. In the event of injury, the blue color will extravasate into the surgical field. May result in transient pulse oximetry decrease. • Positioning. Careful attention should be paid to the positioning and padding of extremities against stirrups and the OR table to prevent nerve injuries.

Extubation/Emergence

• Standard extubation criteria apply • Prophylactic antiemetics; patients have an increased risk, thus multimodal therapy should be considered.

POSTOPERATIVE CARE BED ACUITY

Floor bed is typically appropriate ANALGESIA

• PCA is commonly utilized following general anesthesia. • Transverse abdominis plane block with catheters allows for prolonged administration of local anesthesia for postoperative pain control. • Epidural catheters. Low-dose local anesthetic with opioid provides excellent pain relief; reduces the amount of opioid requirement, and postoperative ileus (3).

COMPLICATIONS

• Excessive bleeding during surgery • Postoperative hemorrhage • Infection • Injury to ureter, bladder, or other pelvic structures • Bowel injury, though it is rare • Blood clots in the veins lead to DVT or PE. Early ambulation reduces the risk of thromboembolism, postoperative morbidity, duration of hospital stay, and hospital costs.

REFERENCES

1. Johnson, Barlow D, Lethaby A, et al. Surgical approach to hysterectomy for benign gynecological disease. Cochrane Database Syst Rev. 2006;2:CD003677.

2. Wright JD, Devine P, Shah M, et al. Morbidity and mortality of peripartum hysterectomy. Obstetric Gynecol. 2010;115(6):1187–1193. 3. Massicotte L, Chalaoui KD, Beaulieu D, et al. Comparison of spinal anesthesia with general anesthesia on morphine requirement after abdominal hysterectomy. Acta Anaesthesiol Scand. 2009;53(5):641–647. 4. Okin C, Guido RS, Meyn LA, et al. Vasopressin during abdominal hysterectomy: A randomized controlled trial. Obstet Gynecol. 2001;97(6):867–872. See Also (Topic, Algorithm, Electronic Media Element) • Epidural • Laparoscopy • Placenta accreta • Insensible fluid loss • Uterine rupture

CLINICAL PEARLS

• Obstetric hemorrhage and postpartum hysterectomy may be decreased by arterial embolization. In placenta accreta, endovascular interventions like prophylactic temporary balloon occlusion or transcatheter embolization of the anterior division of the internal iliac arteries can minimize postoperative hemorrhage AQ Please provide complete detail in ICD code. • Injection of vasopressin into the uterus during abdominal hysterectomy has been shown to reduce blood loss by 40% without increasing morbidity (4). Vasopressin produces vasospasm of uterine vasculature and uterine muscle contractions, thereby reducing blood loss during the procedure. • As an alternative to hysterectomy in cases of symptomatic fibroids, uterine artery embolization may be performed.

I:E RATIO

Siamak Rahman, MD

BASICS DESCRIPTION

• The I:E ratio describes the duration of inspiration to the duration of expiration. – Each complete ventilator breath has an allotted time for inspiration time for inspiration (Itime) before the ventilator must cycle into exhalation time (E-time). – The sum of the I-time and E-time equals the allotted time per breath (total duration). – The ventilator delivers a set number of breaths per minute, or ventilator frequency and this determines the length of each breath. A frequency of 20 would result in 3 seconds/breath whereas a frequency of 10 would result in 6 seconds/breath. • Programming the I:E ratio – Generous I-time allows recruitment of collapsed lung segments. – Adequate E-time avoids gas trapping. PHYSIOLOGY PRINCIPLES

• Inspiratory time. Describes the time over which the tidal volume is delivered (volume control (VC) or the pressure is maintained (pressure control). – Sufficient I-time is needed to allow distribution of the positive pressure inspiratory volume and recruit collapsed lung segments (redistribution of gas from more compliant alveoli to less compliant alveoli). Sustained elevations in airway pressure may recruit lung units more effectively than transient increases. Additionally, sustained alveolar inflation appears to decrease dead space, perhaps by facilitating the delivery of gas to well perfused (less compliant) areas. – Volume-controlled ventilation. As the I-time is increased, peak inspiratory pressures and turbulence decrease; there is more time to deliver the set volume. Decreased peak pressures also allow for improved venous return to the right atrium (and cardiac output) particularly in volume-depleted patients. Inspiratory pause. Following the tidal volume delivery, a pause may be programmed to maintain inflation of the alveoli (optimize ventilation to perfusion). This pause occurs during the programmed I-time: I:E = (inspiratory time + inspiratory pause time):expiration – Pressure-controlled ventilation (PCV). As the I-time is increased, larger tidal volumes and decreased turbulence result; there is more time to recruit collapsed lung segments at a given pressure. • Expiratory time. Sufficient E-time is needed to allow alveoli to empty prior to the subsequent positive pressure inspiratory breath. • Selecting an I:E ratio is a balance between decreasing turbulence and peak pressures and increasing tidal volumes against allowing enough time for exhalation and preserving preload.

– Adults. Normal spontaneous ventilation usually ranges from 1:1.5 to 1:2.5. – Children. The I:E ratio during normal spontaneous ventilation in young children is typically 1:3. • Inverse respiratory ventilation (IRV). In theory, prolongation of the inspiratory time can maintain mean airway pressures (MAP) and tidal volume at lower levels of positive endexpiratory pressure (PEEP) and peak alveolar pressure, provided that excessive endexpiratory gas trapping does not occur.

DISEASE/PATHOPHYSIOLOGY

• Hypoventilation and respiratory acidosis may occur if there is insufficient time for tidal volume delivery or pressure limits are reached prematurely. • Gas trapping occurs if there is insufficient time for alveoli to empty before the next breath. This can result in progressive hyperinflation of alveoli and progressive rise in end-expiratory pressure (known as auto-PEEP) with resultant barotrauma or cardiovascular compromise due to high intrathoracic pressures. Situations where this may result include: – Increased inspiratory time or inverse inspiratory time, compared to expiration – Obstructive disease states such as asthma or chronic obstructive pulmonary disease (COPD) – High respiratory rates, resulting in a shortened absolute expiratory time. Has been observed with high-frequency oscillatory ventilation (HFOV).

PERIOPERATIVE RELEVANCE

• Time cycling is used for pressure, volume, and dual controlled (VC with pressure limits) modes. Either the I:E ratio or inspiratory time is set and flows are adjusted accordingly to ensure that the set tidal volume is delivered. • Volume-cycled. The flow is set and the inspiration ends when the set tidal volume has been delivered. • Hypoxemia not responding to increased FiO2. Inverse I:E ratio can facilitate redistribution of the tidal volume from more compliant to less compliant alveoli. Under general anesthesia this is well-tolerated, but in the awake or mildly sedated patient, this is poorly tolerated. • Acute respiratory distress syndrome (ARDS). Inverse I:E ratios have been utilized to reduce peak inspiratory pressures and barotrauma. Additionally, a long, sustained inspiration reduces the mean airway pressure while increasing the PaO2 for a given FiO2. Despite the

benefits in gas exchange, the prolonged inspiratory duration relative to expiration is uncomfortable for the alert patient, and paralysis may be required. However, the effects of PCV with different I:E ratios on respiratory mechanics, gas exchange, and hemodynamics in patients with adult respiratory distress syndrome have failed to show any short-term beneficial effect of PCV or PCIRV (inverse ratio) over conventional VC with PEEP in patients with ARDS (1).

EQUATIONS See Table

GRAPHS/FIGURES

Measuring intrinsic PEEP: quantitative measurement of intrinsic PEEP can be obtained in an apneic patient by using the expiratory pause hold control on the ventilator. This allows equilibration of pressures between the alveoli and the

ventilator allowing the total PEEP to be measured. The value for total PEEP can be read from the airway pressure dial or the PEEP display.

Intrinsic PEEP = Total PEEP − Set PEEP

REFERENCES

1. Lessard MR, Guérot E, Lorino H, et al. Effects of pressure-controlled with different I:E ratios versus volume-controlled ventilation on respiratory mechanics, gas exchange, and hemodynamics in patients with adult respiratory distress syndrome. Anesthesiology. 1994;80(5):983–991. 2. Marcy TW, Marini JJ. Inverse ratio ventilation in ARDS. Rationale and implementation. Chest. 1991;100(2):494–504. See Also (Topic, Algorithm, Electronic Media Element) • Pneumothorax • Chronic obstructive pulmonary disease • Asthma • Jet ventilation

CLINICAL PEARLS

• Normal, spontaneous ventilation follows an inspiratory to expiratory ratio of 1:2. During mechanical ventilation, the I:E ratio is commonly set to this as well. • In the ventilated patient, the inspiratory time may be increased to improve oxygenation or decrease the peak inspiratory pressures; however it may result in auto-PEEPing, barotrauma, or poor patient tolerance (sedated patients). • Inspiratory pause time is an option in modes where a fixed tidal volume is set and delivered.

IGA DEFICIENCY

Sonia Vaida, MD Chris A. Steel, MD Berend Mets, MB, ChB, PhD, FRCA, FFASA

BASICS DESCRIPTION

• IgA deficiency is defined as a decreased ability or inability to produce IgA antibodies. • Most patients are asymptomatic. However, some patients are more prone to develop recurrent upper respiratory tract infections, lower GI infections, and autoimmune disorders. • Patients with an inability to produce IgA can develop IgA autoantibodies, and are thus at risk for anaphylactic or anaphylactoid reactions when exposed to blood products that contain IgA. EPIDEMIOLOGY Prevalence

• The most common primary immunodeficiency. • 1:700 in people of European descent. • Very low incidence in the Asian population.

Prevalence

• Up to 40% of patients with IgA deficiency can develop autoantibodies to IgA. • In the general population, 1:1,200 have IgA deficiency and anti-IgA antibodies (1). • In the general population, anaphylactic transfusion reactions from IgA deficiency occur in 1:20,000 to 1:47,000.

Morbidity

Possible severe anaphylactic or anaphylactoid reactions to blood or blood products. Mortality Very rare

ETIOLOGY/RISK FACTORS

• Mainly inherited as an autosomal dominant or autosomal recessive trait. However, it can also be acquired (e.g., drug induced and secondary to viral infections). • Patients with absolute IgA deficiency can develop antibodies to IgA and therefore are at risk for severe allergic reactions when transfused with standard, IgA containing blood components.

PHYSIOLOGY/PATHOPHYSIOLOGY

• IgA is a serum immunoglobulin and antibody predominantly found at mucosal surfaces with

an important role in immune protection. • IgA deficiency results from an intrinsic B cell defect, which prevents their differentiation into IgA producing cells (2). The defect seems to involve stem cells. • Patients possess a higher risk of moderate to severe allergic manifestations (1).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• In patients with confirmed or suspected IgA deficiency, obtain IgA levels; if <0.05 mg/dL, test for anti-IgA antibodies. • Blood product options and methods – Packed red blood cells (pRBCs). IgA deficient units may be stored by the blood bank (deglycerolized allows for longer storage times) Alternatively, units can be washed to remove residual plasma (containing donor IgA antibodies) and decrease the risk of anaphylaxis – Fresh-frozen plasma (FFP) and cryoprecipitate are obtained from IgA-deficient blood donors and can be kept frozen for 1 year or in the thawed state for 1–2 days. – Platelets can be obtained from IgA-deficient blood donors or can be washed to remove IgA; however, washing can impair platelet function. – To avoid an allergic reaction, intravenous immunoglobulin G (IVIG) preparation treated with solvent detergent has been utilized to pretreat patients with IgA deficiency and high levels of IgA antibodies prior to transfusion. • If anti-IgA antibodies are present, surgery is elective, and blood transfusion is expected, then IgA-deficient blood and blood products should be obtained. Discuss the availability of IgAdeficient blood and blood products with the blood bank pathologist. • In a life-threatening situation, do not withhold blood or blood products based on an unknown risk of a transfusion reaction (1). Ideally, IgA-deficient products should be administered, if available. If not, pretreat with 200 mg hydrocortisone IV and 50 mg diphenhydramine IV, and administer washed pRBCs or platelets. FFP or cryoprecipitate may be administered after pretreating the patient and monitoring closely for signs of a reaction.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Most patients are asymptomatic and diagnosed coincidentally. • May be identified among blood bank donors.

History

• Consider IgA deficiency in patients with a history of recurrent acute respiratory infections (sinusitis, pneumonia, etc.) • Determine how the patient was diagnosed with IgA deficiency. • History of anaphylactic reactions associated with transfusion of blood; if so, determine if IgA levels and IgA antibodies were identified.

Pediatric Considerations

Gravid patients with known IgA deficiency should have anti-IgA antibody levels checked and

the availability of specific blood products should be discussed with the blood bank pathologist. If the patient has an increased risk for bleeding (e.g., placenta previa), a Cesarean section should be scheduled and IgA-deficieny blood products should be available (3).

Signs/Physical Exam

Signs of bronchiectasis may be present in some patients with recurrent pneumonias. TREATMENT HISTORY

• Patients with severe or frequent infections from IgA deficiency can be candidates for IVIG. • The best way to avoid triggering a reaction is to simply avoid exposing patients with antiIgA antibodies to blood products with IgA. • When this is unavoidable in an emergent situation, the patient should be pretreated as previously mentioned and monitored closely for signs of a reaction. MEDICATIONS

• No specific medication is available. • Pulmonary, GI, or autoimmune disorders should be treated accordingly.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• IgA levels. Know your laboratory’s lower limit of IgA detection. • Anti-IgA antibody presence.

CONCOMITANT ORGAN DYSFUNCTION

• Pulmonary: Recurrent upper respiratory infections (bronchitis, pneumonia), otitis media, asthma • GI: Recurrent GI infections, chronic diarrhea. • Autoimmune diseases: Celiac disease, Graves’s disease, systemic lupus erythematous, rheumatoid arthritis • Lymphoid malignancies

CIRCUMSTANCES TO DELAY/CONDITIONS

If anti-IgA antibodies are present, and there is a likelihood that blood or blood products will be needed, delay elective surgery and obtain IgA-deficient products. CLASSIFICATIONS

IgA1 and IgA2 subclasses

TREATMENT PREOPERATIVE PREPARATION Premedications

Diphenhydramine and corticosteroids can be administered in emergency situations if IgA levels and/or anti-IgA antibody presence are unknown prior to transfusion of standard blood

products.

INTRAOPERATIVE CARE Choice of Anesthesia

No preference for a type of anesthesia. Monitors

• Standard ASA monitors • Consider invasive monitors in a patient with anti-IgA antibodies and expected bleeding/transfusion.

Induction/Airway Management No preference Maintenance

• No preference • In general, when administering blood products, there should be vigilance for flushing, wheezing, bronchospasm, hypotension, or other clinical signs of anaphylaxis. • If an allergic reaction is suspected, stop the transfusion and administer hydrocortisone and diphenhydramine. • In patients with known IgA deficiency, consider autologous blood transfusion or cell salvage. Also prepare the IgA-deficient or washed blood products prior to the case or as soon as possible.

Extubation/Emergence No preference

FOLLOW-UP BED ACUITY

The reaction between IgA and anti-IgA antibodies would occur shortly after administration of products containing IgA. If no significant reaction is noted, a delayed anaphylactic reaction is unlikely. MEDICATIONS/LAB STUDIES/CONSULTS

• Should an anaphylactic reaction occur: – Stop blood transfusion – Administer IV fluids – Maintain hemodynamic parameters with epinephrine in low doses (if needed) – Type and cross match – Perform a direct antiglobulin test and an IgA antibody test (if not already ordered). • Blood product is considered IgA deficient if the serum IgA is <0.05 mg/dL.

COMPLICATIONS

• Possible anaphylactic reaction to blood or blood products

• Be prepared to treat anaphylaxis • Epinephrine should be ready to administer

REFERENCES

1. andler SG. How I manage patients suspected of having had an IgA anaphylactic transfusion reaction. Transfusion. 2006;46:10–13. 2. Yel L.Selective IgA deficiency. J Clin Immunol. 2010;30:10–16. 3. Steel C, Vaida S, Mets B. Massive blood transfusion in a patient with immunogobulin a deficiency undergoing cesarean delivery. Anesth Analg. 2010;110:1088–1090.

ADDITIONAL READING

• Flickinger C, Petrone T, Church A. A review: American rare donor program. Immunohematology. 2004;20:239–243. • Gilstad CW. Anaphylactic transfusion reactions. Curr Opin Hematol. 2003;10:419–423.

See Also (Topic, Algorithm, Electronic Media Element) • Anaphylaxis

CODES ICD9 279.01 Selective IgA immunodeficiency ICD10 D80.2 Selective deficiency of immunoglobulin A [IgA]

CLINICAL PEARLS

• Patients are advised to wear an identification bracelet. • There is an IgA-deficient blood donor registry (consult American Rare Donor Registry). • If testing for IgA is not available before urgent transfusion, do not withhold transfusion with standard blood products.

INFECTIOUS DISEASE EXPOSURE IN THE HEALTHCARE WORKER Russell K. McAllister, MD Andrew L. Barker, MD

BASICS DESCRIPTION

• Working in the healthcare setting necessitates a degree of exposure to infectious hazards that is greater than non-healthcare-related jobs. – Parenteral injury, inhalational exposure, and direct contact with bodily fluids are the primary means of communication or exposure. – The most common parenterally transmitted diseases are HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV). – Universal precautions should be the standard. Additional precautions must be taken for airborne pathogens such as tuberculosis, H1N1 influenza, and human papillomavirus (HPV). • Agents used in bioterrorism attacks have become increasingly more important for the healthcare provider to be familiar with. EPIDEMIOLOGY Prevalence

• There are ~800,000 percutaneous injuries per year in the US. Most needlesticks occur in the OR from suture needlesticks. • HIV seroconversion after a needle stick from an HIV positive patient is 0.3%; in 2004, 57 healthcare workers reported contracting HIV in the workplace. • Hepatitis B seroconversion after parenteral exposure can vary between 2% and 40% for the nonimmunized. Since the introduction of the hepatitis B vaccination, infections have decreased from 10,721 in 1983 to 384 in 1999 (a 96% reduction). • Hepatitis C seroconversion after parenteral exposure is estimated at 1.3%. • Tuberculosis infection among all healthcare workers has an incidence ranging from 3.6 to 5.4 workers per 100,000 from 1994 to 2000. • HPV infection following inhalational exposure is unknown; most likely very rare.

Morbidity/Mortality

• HIV infects ∼5 million people worldwide annually. Roughly 900,000 cases of AIDS were reported in the US in 2002. With appropriate antiretroviral therapy early in the disease course, HIV patients have a life expectancy between 20 and 50 years. Without treatment, however, the median life expectancy is estimated to be between 9 and 11 years from the time of infection. The major cause of death is opportunistic infections in the later stages of the disease.

• Hepatitis B causes asymptomatic disease in 60–65% of infected people, acute hepatitis in 20–25% of infected people, and chronic hepatitis in roughly 1% of people. • Hepatitis C causes active liver disease in 75–80% of infected people, cirrhosis in 10–20% of infected people, and liver cancer in 1–5% of cirrhosis patients. • New, active tuberculosis infections affect 16,000 people per year in the US. Forty-five percent of these infections occur in immigrants. In 10–50% of immunocompromised hosts, the bacteria migrate to various organs and cause a disseminated disease. The major cause of death is due to lung disease. • Laryngeal papillomatosis does not cause a malignant disease, but frequently causes recurrent papillomas that require multiple operations for treatment. • Creutzfeldt–Jakob disease affects ∼1 in 1,000,000 people each year. It is uniformly fatal and has an average duration of 7 months.

ETIOLOGY/RISK FACTORS

• Parenteral infections – Wearing gloves has been shown to decrease the frequency of seroconversion from needlestick injuries. Likewise, gloves prevent transmission of infection via open skin wounds on the hands. – Percutaneous injuries from smaller gauge needles have a lower incidence of seroconversion than larger needles. This is likely due to the degree of tissue trauma inflicted by the needle, as well as the viral load being transferred on the needle itself. – Hollow bore needles have a higher rate of seroconversion than solid (suture) needles. – Transmission from a patient with a high viral load has a higher incidence of seroconversion than when a patient has a lower viral load. • Inhalational infections – Personal protective equipment like an N95 mask has been shown to reduce the transmission of inhaled infections to healthcare workers. – Negative pressure rooms prevent bacteria transmitted by the inhalational route from being released into hallways and other rooms. – When using a laser on HPV lesions, a suction device can be used to collect aerosolized virions and is thought to reduce the risk of transmission of the virus. • Prion diseases – The only known risk factor for prion disease transmission is direct contact with infected patient material. Creutzfeldt–Jakob disease is the most common prion disease worldwide, and 85–90% of cases arise spontaneously rather than via an infectious route. • Bioterrorism agents – Anthrax, Yersinia pestis (plague), smallpox, and Clostridium botulinum are among the most common agents used in bioterrorism. – The most significant risk factor for infection with these agents is direct exposure. There are no documented modifiable risk factors for these diseases other than standard universal precautions. PHYSIOLOGY/PATHOPHYSIOLOGY

• HIV is a retrovirus that infects human macrophages and CD4+ T-cells. • Hepatitis B is a DNA virus that replicates primarily in hepatocytes.

• Hepatitis C is an RNA virus that also preferentially infects hepatocytes. The direct cytotoxic effects on the hepatocyte are thought to be responsible for the bulk of the damage caused by hepatitis C, in contrast to the immune-mediated cytotoxic effects of hepatitis B. • Tuberculosis is caused by Mycobacterium tuberculosis. Tuberculosis typically leads to a latent infection in the apical portions of the lung. However, an assortment of factors can cause the bacteria to reactivate or disseminate into the blood stream, causing miliary tuberculosis. The major cause of organ dysfunction is due to the caseating necrosis caused by the immune response to the bacteria and surrounding structures. • HPV can be disseminated into the healthcare environment via surgical lasering of infected lesions. These virions can be inhaled into the respiratory tract and may (rarely) cause an infection of laryngeal or other airway structures. Infection primarily causes laryngeal papillomatosis, which can lead to hoarseness or airway obstructions. Treatment focuses on removal of the papillomas with a laser. • Influenza A is caused by the influenza virus. Symptoms include fever, myalgias, sore throat, and pneumonia that may be fatal. • Bacillus anthracis is a large spore-forming, Gram positive, rod-shaped bacteria that causes anthrax. Anthrax’s prodrome consists of a fever, cough, and chest or abdominal pain. The prodrome is typically 1–6 days in duration, but disease progression is imminent when the fever acutely worsens. This is rapidly followed by hypoxia and possibly death. • Smallpox virus is spread by the respiratory aerosol route or contact with infected bodily fluids. It causes symptoms 7–17 days after infection, which first consist of fever, headache, and/or backache. The characteristic rash starts on the mucosa of the oropharynx, face, and extremities. The rash becomes vesicular and pustular in its later stages as it migrates toward the trunk. Mortality is 30% or greater. • Yersinia pestis is the causative agent of the plague. The bacteria have an array of mechanisms to avoid host defenses while weakening the immune system. Depending on the route of infection, symptoms can include pustules and ulcerations of the skin or hemorrhagic, necrotizing pneumonia. Fulminant bacteremia with resultant disseminated intravascular coagulation, hemorrhages, and thrombi are the major causes of death. • Botulism is caused by Clostridium botulinum, a spore-forming, Gram-negative rod found in inadequately sterilized canned foods. The neurotoxin produced by the bacteria prevents the release of neurotransmitters, which results in paralysis. Without supportive care, mortality is estimated at 60%. With supportive care, however, mortality is estimated at 5–10%. • Creutzfeldt–Jakob disease and other spongiform encephalopathies are caused by prions. Prions are proteins that have had a spontaneous conformational change in their tertiary structure. This conformational change causes a chain reaction, which leads to massive neural degeneration. The most common presenting symptom is dementia, which progresses to a uniformly fatal encephalopathy. PREVENTATIVE MEASURES

• Universal precautions should be taken in all situations. Appropriate eye care, gloves, and personal protective equipment should be made available in any location where healthcare personnel may come into contact with infected patients or bodily fluids. • Needleless IV tubing may reduce risk. • One-handed needle recapping

• Hospital policies mandating appropriate isolation for high-risk patients should be in place. There should be appropriate warning signs to alert all healthcare personnel of possible exposure.

PREOPERATIVE ASSESSMENT • The constellation of physical examination findings will differ based on the specific infectious disease in question. • All exposures need to be appropriately reported to employee health; after hours, the emergency room or infectious disease on-call person usually has the capability of initiating the workup and therapy as needed. • Specific screening tests following exposure to various infectious diseases are dictated by the route of injury. • For percutaneous injuries, HIV, hepatitis B, and hepatitis C titers should be drawn as soon as possible following the injury. • Following initial titers, repeat screening should be performed at given intervals based on the disease in question. • For tuberculosis, PPD screening should be performed on an annual basis for all healthcare providers.

DIFFERENTIAL DIAGNOSIS

Will vary depending on the specific infectious agent.

TREATMENT • Healthcare workers who are exposed to HIV should be considered for a 4-week course of treatment with a combination of zidovudine and lamivudine, lamivudine and stavudine, or didanosine and stavudine. Resistant strains can occur. • Hepatitis B exposures should be treated with prompt institution of the hepatitis B vaccine series in individuals who have not already completed the series. In addition to the vaccination series, hepatitis B immune globulin should be considered for patients who have not completed the vaccination series OR who have an inadequate response to a completed vaccine series. • Hepatitis C exposures are not treated with immune globulin or antiviral agents (interferon, with or without ribavirin). Only follow-up testing should be performed. • Anthrax should be treated by a 60-day course of ciprofloxacin or doxycycline. If the bacteria are known to be penicillin sensitive, however, the treatment should be a 60-day course of penicillin G or amoxicillin. • Smallpox has no definitive therapy. Secondary infections should be treated on an as needed basis should they arise. • Yersinia pestis is highly transmissible and requires respiratory/droplet isolation until at least 3 days of antibiotic therapy has been completed. Treatment can include a 10-day course of streptomycin, gentamicin, doxycycline, or ciprofloxacin. • Botulism should be treated with supportive care, which may include prolonged mechanical

ventilation. In addition, specific antitoxins are available based on bacterial serotype. • There is no known cure or therapy for prion diseases such a Creutzfeldt–Jakob disease. The only action currently known to be effective is to prevent further spread of disease by limiting exposures of uninfected individuals.

FOLLOW-UP Determined by the disease in question

REFERENCES

1. elay ED. Transmissible spongiform encephalopathies in humans. Annu Rev Microbiol. 1999;53:283–314.

2. Centers for Disease Control and Prevention. Novel influenza A infections among healthcare personnel – United States, April-May 2009. 2009;58(23):641–645. 3. Garden JM, O’Banion MK, Shelnitz LS, et al. Papillomavirus in the vapor of carbon dioxide laser-treated verrucae. JAMA. 1988;259(8):1199–1202. 4. Centers for Disease Control and Prevention. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. 2001;50(RR11):1–42. 5. Fine A. New York State Department of Health. Summary of biological warfare agents. 2001. 6. Texas Department of State Health Services. Texas contaminated sharps injuries, 2008. Available at: http://www.dshs.state.tx.us/idcu/health/infection_control/bloodborne_pathogens/report/20 (accessed February 15, 2011.

See Also (Topic, Algorithm, Electronic Media Element) • Radiation safety • Hepatitis C

CODES ICD9 V01.9 Contact with or exposure to unspecified communicable disease ICD10 Z20.9 Contact w and exposure to unsp communicable disease

CLINICAL PEARLS

• Vigilance and prevention are the most effective ways to avoid transmission of diseases. • Following exposure, certain diseases can be treated with postexposure prophylaxis in order

to decrease the rate of infection. • The carrier rate among healthcare workers for methicillin-resistant Staphylococcus aureus (MRSA) may be as high as 1 in 20 (approximately 2–3 times greater than the general population). Only about 5% of those have symptoms. Healthcare workers may be 2–3 times more likely to be a carrier of MRSA. • Healthcare workers are considered to be at significant risk for acquiring or transmitting hepatitis B, influenza, measles, mumps, rubella, and varicella. All of these are preventable by vaccines. Immunocompromised healthcare workers are at a greater risk and the Centers for Disease Control issue vaccination recommendations for this population.

INFRARENAL AAA REPAIR E. Gail Shaffer, MD, MPH Richard McAffee, MD

BASICS DESCRIPTION General

• Although endovascular aortic repair (EVAR) is gaining popularity, open repair of infrarenal abdominal aortic aneurysms remains an important treatment option. Additionally, it may be carried out after endovascular repair has been attempted and failed. • The choice between open versus endovascular repair depends on many factors including surgeon preference, patient preference, aneurysm characteristics (size, shape, and location), and comorbidities. • Following careful dissection and exposure of the aneurysm, the patient is heparinized. The aortic cross-clamp is first placed distally (to prevent atheroembolic events) and then proximally. For infrarenal AAAs, clamping usually occurs below the level of the renal arteries; however, suprarenal clamping may be necessary in some situations. • The graft is first sutured proximally, then a clamp is placed on the graft. The proximal aortic clamp is removed, and the proximal suture line is examined for bleeding. • The graft is then sutured distally to the aorta or iliacs, the graft clamp is removed and flow is assessed. If there are no leaks, the distal clamps are removed. • Reversal of heparin with protamine should be discussed with the surgeon.

Position

• Supine for transperitoneal approach • Supine with left flank elevation for retroperitoneal approach

Incision

• Transperitoneal: Midline abdominal • Retroperitoneal: Oblique incision along 10th rib extending toward umbilicus

Approximate Time 2–5 hours

EBL Expected

• Approximately 500 mL • Ruptured AAAs have increased loss

Hospital Stay

• Open repair: 5–10 days • Ruptured AAA: 10 days or greater

Special Equipment for Surgery

• Preparation for large volume blood loss may include cell salvage and rapid infuser • Neuromonitoring is not typically used, but may be considered for extensive, “re-do” AAA repairs, or for thoracic AAA repairs.

EPIDEMIOLOGY Incidence

• Newly diagnosed: ∼200,000/year • AAA repairs: 35,000–40,000/year; over 50% are performed via open repair • Conversion to open from EVAR: ∼3%

Prevalence

• More prevalent with age, significant smoking history, hypertension (HTN), male gender, family history, and connective tissue disease. • Biggest predictors of risk of rupture are the diameter and rate of expansion.

Morbidity

Open repair has a higher morbidity and mortality than EVAR; however, this difference is not significant when comparing long-term survival. Mortality

Elective AAA repair 28-day mortality ranges from 3.3% to 27.1% in men and 3.8% to 54.3% in women; 5 year mortality from 12.9% to 78.1% in men and 24.3% to 91.3% in women. Age, congestive heat failure, cerebrovascular disease, and diabetes are independent risk factors for 5-year mortality. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients may present with multiple comorbid issues that need to be independently assessed and optimized. • Wide hemodynamic shifts can be seen with clamping and unclamping of the aorta; the anesthesia provider must be in constant communication with the surgeon as well as understand the physiological changes and treatment modalities at each stage.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Expanding AAA may present with pain • Pulsatile mass may cause back and stomach pain

History

• Often asymptomatic • Elicit history of cerebral, cardiac, renal, and peripheral vascular disease

Signs/Physical Exam

Palpable abdominal mass and bruits may or may not be present. MEDICATIONS

• Beta-blockers can reduce cardiac morbidity and mortality (DECREASE study) and should be continued perioperatively. Heart rate (HR) control and decreased contractility result in less systolic pressure generated against the aneurysm wall. • Statin’s pleiotropic effects can reduce postoperative cardiac, cerebral, and renal morbidity; should be continued perioperatively. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, BUN/Cr • Hemoglobin/hematocrit • Coagulation parameters (PT, INR, PTT) • EKG (further cardiac workup is based on symptoms and EKG results). • CXR if significant smoking history, chronic obstructive pulmonary disease (COPD) • Cardiac evaluation may include stress testing and cardiac catheterization.

CONCOMITANT ORGAN DYSFUNCTION • Peripheral vascular disease • Cerebrovascular disease • COPD

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics as needed; anxiety may increase BP and the risk of AAA rupture. • Beta-blockers have been shown to reduce morbidity and mortality in major vascular surgical patients; titrate to a HR <80 bpm. • Perioperative statin therapy initiation may be indicated. • Cross-matched blood products should be in the room.

Special Concerns for Informed Consent • Potential for blood transfusion • Invasive monitoring • Postoperative intubation in the ICU

Antibiotics/Common Organisms

Skin flora; first-generation cephalosporin such as cefazolin INTRAOPERATIVE CARE Choice of Anesthesia

General endotracheal anesthesia +/– T8 epidural placement for postoperative analgesia. Monitors

• 2 large-bore IVs • Arterial line; consider preinduction placement • Central venous catheter should be considered for pressure monitoring and inadequate PIV access • Pulmonary artery catheter for pulmonary artery pressure (PAP), MVO2, CO, SVR monitoring based on comorbidities • Foley catheter • TEE depending on comorbidities

Induction/Airway Management

• A slow, controlled induction is necessary to ensure an adequate depth of anesthesia and minimize hemodynamic changes. Hypotension can impair perfusion; HTN can result in aneurysmal rupture (transluminal pressures, coughing, bucking, etc.). • Epidural is advantageous for postoperative pain; it is often prudent to wait until after the aorta is unclamped and hemodynamics have stabilized to bolus the epidural and begin an infusion.

Maintenance

• Balanced volatile or IV techniques may be utilized. • Cross-clamping of the aorta – Preload: Variable increase (minimal to significant) – Afterload is increased by the clamp. The more distal the clamp, the less increase in afterload. Compensatory vasodilation above the clamp occurs. Patients with poor left ventricular (LV) function may not be able to tolerate the increase in myocardial work and oxygen consumption. Myocardial ischemia and “flash” pulmonary edema can result if not properly anticipated. Treatment is with vasodilators at the time of clamping (nitroprusside, nicardipine, propofol). – HR: No change typically. – Contractility will increase in a normal heart; in those with CAD or CHF, the heart may not be able to compensate. – Cardiac output: No change (or decreased in the setting of LV dysfunction). – SVR distal to the clamp is increased to maintain perfusion; thus the administration of vasodilators to decrease myocardial afterload may impair perfusion pressure. Distal tissue hypoxia results in anaerobic metabolism with lactic acid production and the accumulation of vasoactive metabolites (oxygen free radicals, cytokines, and prostaglandins). • Unclamping of the aorta – Preload decreases as vasodilated arterial beds fill with blood; volume loading should be performed prior to unclamping. – Afterload is abruptly decreased. Consider initiating phenylephrine or norepinephrine drip a few minutes prior to anticipated release of cross-clamp or bolusing as needed. – HR: May reflexively increase in response to hypotension – Contractility: Washout of metabolites from distal ischemia may impair inotropy; consider

the use of inotropes. – Cardiac output changes are variable; if adequately volume loaded, the abrupt drop in afterload favors a high cardiac output; however, hypovolemia or ischemic metabolites more often lead to a decreased cardiac output. – PAP can increase from hypercarbia, acidosis, and ischemic metabolites. – If hypotension cannot be medically managed, it may be necessary for the surgeon to reclamp the aorta. • Renal perfusion may be compromised. Renoprotective measures are limited to maintaining adequate volume status, avoiding hypoxemia and hypoperfusion, and administering mannitol and sodium bicarbonate. • Maintain normothermia with active warming devices (forced air warmer, etc.) to counteract anticipated heat loss from large incision, visceral exposure, skin open to room air, and prolonged operative time. • Volume replacement: May have large insensible losses. Significant blood loss may be possible, especially with ruptured AAA.

Extubation/Emergence

• Standard extubation criteria; special attention to blood loss, hemodynamics, and normothermia. Complicate surgeries or comorbid conditions may warrant leaving the patient intubated postoperatively. • Smooth extubation (avoid coughing and bucking). • Control of HTN and tachycardia is important; consider beta-blockers and/or vasodilators (bolus or drips). • Postoperative neurologic exam should evaluate cerebral and peripheral ischemia.

POSTOPERATIVE CARE BED ACUITY

• ICU bed for most patients • Close control of BP to decrease bleeding from graft site, often requiring vasoactive infusions

ANALGESIA

• Patient may have significant pain. • If an epidural catheter is present, ensure that the level of coverage, rate, and concentration are adequate. Catheter removal may be performed after ensuring that the coagulation status is normal.

COMPLICATIONS

• Cardiac complications such as myocardial ischemia or infarction, HTN (most common) • Hemorrhage or coagulopathy • Lower extremity or bowel ischemia • Renal failure • Respiratory failure

PROGNOSIS

• Incidence of reoperation is less with open repair compared to EVAR. • Late graft complication with open repair is very low (less than 2.5%). • 30-day mortality is higher compared to EVAR; however, no difference is observed at 12 months.

REFERENCES

1. Eliason JL, Clouse WD. Current management of infrarenal abdominal aortic aneurysms. Surg Clin N Amer. 2007;87(5):1017–1033. 2. Mantha S, Ochroch EA, Roizen MF, et al. Anesthesia for vascular surgery. In: Barash PG, Cullen BF, Stoelting RK, eds., Barash Clinical Anesthesia. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:1122–1133. 3. Moulakakis KG, Dalainas I, Myloas S, et al. Conversion to open repair after endografting for abdominal aortic aneurism: A review of causes, incidence, results, and surgical techniques of reconstruction. J Endvasc Ther. 2010;17(6):694–702. 4. Poldermans D, Boersma E, Bax JJ, et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. New Engl J Med. 1999;341(24):1789–1794. See Also (Topic, Algorithm, Electronic Media Element) • Abdominal aortic aneurysm • Abdominal aortic aneurysm (endovascular repair, EVAR)

CODES ICD9 441.4 Abdominal aneurysm without mention of rupture ICD10 I71.4 Abdominal aortic aneurysm, without rupture

CLINICAL PEARLS

• Open infrarenal AAA repair is a major vascular surgery that requires close collaboration between the surgeons and anesthesia providers. • Patient population with significant comorbidities; unless evidence exists otherwise, assume all patients have vascular disease of the heart and cerebrum. • Wide hemodynamic shifts from aortic cross-clamp and release need to be anticipated. In discussion with the surgeon, these shifts can be minimized with pharmacologic intervention. • Hemodynamic shifts from rapid blood loss are also possible – blood should be in the room before incision and large bore IV access is essential.

INSENSIBLE FLUID LOSSES Ashley Greene, DO Mary E. McAlevy, MD

BASICS DESCRIPTION

• Insensible fluid losses are defined as losses of fluid secondary to evaporation into the environment. They are – Difficult to measure and ascertain – Involve estimates that are calculated from clinical experience – Replaced with either crystalloid or colloid; controversy exists as to the preferred fluid. Ultimately, the principal goal should be to optimize cardiac output. • Common sources of insensible losses include – Open wounds, in particular abdominal incisions and exposure – Condensation in the breathing circuits – Sweating – Fever – Hyperventilation • Insensible losses differ from “third spacing” (transcellular movement of fluids) or temporary sequestration (movement of fluid into functionless spaces). These can result from inflammation, trauma, or damage to the normal integrity of the vascular barrier PHYSIOLOGY PRINCIPLES

• The current practices of managing insensible losses are hypotheses; interestingly enough, there are no current studies that have proven that they are significant and need substantial replacement. • Perioperative fluid therapy of insensible losses are guided by the following assumptions: – The preoperative patient is volume depleted as a result of fasting, continued physiologic insensible loss, and urine output. – Intraoperatively, insensible fluid loss to the environment increases with the size of the surgical incision, amount of tissue exposed, and duration of exposure. – Insensible fluid losses require replacement Basal insensible loss. Mainly transdermal and estimated to be at most 0.5 mL/kg/hour and may increase to 10 mL/kg/hour with major abdominal surgery. Size of incision. Insensible loss increases proportionally in relation to the surface area exposed to the environment. Nonhumidified gases. Patients breathing nonhumidified gases have an increase in their insensible losses. This is further accentuated if the patient is hyperventilated. ANATOMY • Abdomen

• Muscle • Thorax

PHYSIOLOGY/PATHOPHYSIOLOGY

• Both hypovolemia and hypervolemia can have deleterious effects. In the perioperative period, anesthesia providers rely on physical examination, vital signs and monitors, as well as laboratory values to assess volume status and guide therapy. • Hypovolemia. Decreases ventricular preload and hence stroke volume (Frank–Starling). Initially, the body may be able to compensate by increasing the heart rate and systemic vascular resistance. However, as hypovolemia progresses, the cardiac output can be impaired and organ hypoperfusion and dysfunction can result. Outcome studies have also shown that it can prolong hospital stay. – History. NPO status, fever, diarrhea, vomiting. Intraoperative blood loss, size of incision. – Physical exam. Dry mucus membranes, decreased skin turgor, decreased capillary refill, sunken fontanelles in newborns, increased heart rate, decreased BP, decreased urine output, and changes in mental status (awake patient) – Laboratory values. Hemoconcentration, hypernatremia, and an increased BUN:Cr ratio (>20:1) – Invasive monitors. Arterial line, central venous monitoring, pulmonary artery catheters, and transesophageal echocardiogram may be used in conjunction with, and to correlate, the overall clinical picture. • Hypervolemia. Can lead to pulmonary edema and increased myocardial oxygen demand (increased preload and wall tension). – History. Ins and outs – Physical exam. Edema (likely pitting), wheezing, crackles on lung exam, increased urinary output, jugular venous distention. In the awake patient, cough and dyspnea. – Laboratory values. Hyponatremia, decreasing Hct levels (due to hemodilution), and increased A-a gradient or decreased a/A ratio.

PERIOPERATIVE RELEVANCE

• Much of current practice on fluid management is based on algorithms that propose replacement of – Preoperative deficits (e.g., NPO status and bowel prep) – Maintenance requirements – Surgical losses – Insensible fluid and third space losses • Perioperative loss of fluid can be broken down into continuous loss (urine output and insensible perspiration) and losses exclusively from trauma (mainly blood loss). In the awake patient, continuous losses are replaced via the GI tract through the absorption of colloid-free fluid and electrolytes. However in the “fasted” patient this mechanism may fail and deficit replacement is performed by the anesthesia provider with crystalloid fluid. • The principal goal of fluid management should be to optimize cardiac preload. • Controversy and considerations – Outcomes. Fluid management can have effects on nausea and vomiting, tissue perfusion, pain, need for surgical revision, length of hospital stay and bowel motility, among other

things. – Generous fluid resuscitation during laparoscopic procedures can decrease both postoperative pain and the incidence of nausea and vomiting in patients prone to PONV. – Errors with measurement. Insensible losses are difficult to accurately calculate, unlike blood loss that can be visibly ascertained. It is often largely overestimated in clinical practice, and many feel that it is negligible and should not be included in maintenance requirements. – Volume status. A clinical impression is based on several variables. At this time, direct blood volume measurements are not available to the anesthesia provider. – Colloid versus crystalloid. Many proponents still advocate that maintenance requirements and preoperative deficits should be replaced with crystalloid solution while blood loss should be replaced with colloid solution. – Fluid restriction. “Optimizing does not mean maximizing.” Newer studies are challenging the current “standard” views of fluid therapy. In fact, some experts advocate not replacing perceived preoperative deficits, but instead fluid “restricted” strategies during the perioperative period (especially during major elective GI procedures). This theory is based on an increasing number of reports that demonstrate that excessive intravascular volume can lead to an increase in morbidity and mortality. Overhydration can lead to pulmonary edema, increased ICU duration, ileus, and abdominal compartment syndromes. – Anesthetic drugs commonly result in decreased systemic vascular resistance and vasodilation. This can unmask hypovolemia or relative hypovolemia (e.g., chronic hypertensives with increased vascular tone, but decreased intravascular volume).

GRAPHS/FIGURES See Table

REFERENCE

1. Chappell D, Jacob M, Hofmann-Kiefer K, et al. A rational approach to perioperative fluid management. Anesthesiology. 2008;109:723–740. 2. Joshi GP. Intraoperative fluid restriction improves outcomes after major elective gastrointestinal surgery. Anesth Analg. 2005;101:601–605. 3. Matthias J, Daniel C, Markus R. The “third space” – Fact or fiction? Best Pract Res Clin Anaesthesiol. 2009;23:145–157. 4. Gan TJ, et al. Goal-directed intraoperative fluid administration reduces length of hospital stay after major surgery. Anesthesiology. 2002;97(4):820–826. See Also (Topic, Algorithm, Electronic Media Element)

• Crystalloids • Colloids • Extracellular fluids

CLINICAL PEARLS

• Controversy exists on how to best manage insensible fluid losses in regard to

– How to accurately measure? – Whether to replace with colloid versus crystalloid fluids – Should a “restrictive” strategy be utilized? Studies have suggested that it may improve outcome; however, the patient’s health, type of surgery, and outcome being measured have not been standardized across these studies. • At this time, the goal remains to maintain intravascular volume status, as both under and over resuscitation can be hazardous. • Goal-directed plasma volume expansion during the intraoperative period may be associated with improved outcome: – Reduction in hospital stay – Earlier return of GI function – Decreased postoperative complications.

INTERNATIONAL NORMALIZED RATIO (INR) Jason Han Chua, MD Anahat Dhillon, MD

BASICS DESCRIPTION

• INR reports the international normalized ratio of prothrombin time (PT), which is a measurement of the extrinsic and final common pathways of coagulation. • The extrinsic pathway is triggered in vivo by tissue injury and the release of tissue factor. • PT is performed in vitro by recalcification of patient blood in the presence of tissue factor; PT is the time in seconds when fibrin clot forms (measured by visual, optical, or electromechanical methods). • Normal values for PT are usually between 12 and 15 seconds depending on the lab, hence the need for a normalized ratio that is unitless. • INR is the most frequently ordered test to monitor warfarin anticoagulation.

PHYSIOLOGY PRINCIPLES

• Extrinsic pathway – Initiated by tissue factor release via tissue injury. – Rapidly proceeds to the final common pathway via factor VII and calcium. • Common pathway – Begins with assisted activation of factor X (by intrinsic or extrinsic pathway). – Factor Xa converts prothrombin to thrombin, which in turn converts fibrinogen to fibrin monomer, which crosslinks to form stable clot with calcium and factor XIII. – Factor X also serves to initiate platelet-surface clotting activity, a vital component of the clotting cascade (greatly accelerates overall clot formation). • Role of thrombin – Positive feedback via activation of cofactors V and VIII. – Accelerates fibrin crosslinking via factor XIII activation. – Stimulates platelet adhesion and aggregation. – Releases tissue plasminogen activator from endothelium, facilitating clot resorption. – Activates protein C (negative feedback via inactivation of factors Va and VIIIa). ANATOMY

PT is sensitive to reduced activity of vitamin K-dependent factors (II, VII, IX, X, C, S), which are produced in the liver. PHYSIOLOGY/PATHOPHYSIOLOGY

• Prolongation of INR – Warfarin; most common cause – Vitamin K deficiency (malnutrition or prolonged use of antibiotics)

– Hepatic dysfunction. Mild dysfunction may lead solely to PT prolongation due to predominant deficiency in factor VII; more severe dysfunction may prolong PT and activated PTT (aPTT) due to a decrease in vitamin K-independent factors. – Other deficiency or inhibition of factors II, V, VII, X, or fibrinogen – Rarely, antiphospholipid antibodies can have antithrombin activity; it is usually associated with a hypercoagulable state. • Alternate assays include – Chromogenic factor X – Prothrombin-proconvertin time (not available in the US) • Mixing study: INR abnormality in the absence of warfarin administration may be due to factor deficiency or inhibition. Differentiation is accomplished via a mixing study, where patient plasma is mixed 1:1 with pooled plasma. – Deficiency: Normalization after dilution. Specific factor assays can reveal the specific factor deficiency. – Inhibition: Continued abnormality after dilution.

PERIOPERATIVE RELEVANCE

• Warfarin’s anticoagulation effect is mediated via inhibition of vitamin K-dependent gammacarboxylation of factors II, VII, IX, and X. – Factors remain immunologically detectable, although biologically inactive. – Full anticoagulation does not take place until preformed, normal factors are cleared, which usually takes 36–72 hours. – PT may be prolonged sooner due to the short half-life of factor VII (5–7 hours); recall, however, that the intrinsic pathway does not require factor VII. – Proteins C and S have shorter half lives than the other vitamin K-dependent factors, and thus a theoretical risk exists for hypercoagulability early after initiation of warfarin therapy. Skin necrosis has been described when used to treat protein C deficiency. – Equilibration of factor levels usually occurs at least 1 week after initiation of therapy. – Target INR varies depending on the patient’s indication for warfarin therapy, but is typically between 2.0 and 3.0. • Abnormal INR – May be seen with first year warfarin therapy, age >65 years, hypertension, alcoholism, liver disease, stroke, and history of GI bleeding. – Patients with prolonged INR and any of the above risk factors undergoing major surgery with significant expected blood loss may benefit from preoperative correction of INR (via vitamin K in elective procedures or fresh frozen plasma in emergent procedures). • When considering a neuraxial anesthetic technique in an anticoagulated patient, ASRA consensus is to document a normal INR prior to placing the neuraxial block and an INR <1.5 when removing an epidural catheter. – Concern is for epidural hematoma, which may cause spinal cord compression with devastating neurologic consequences. – Regular neurologic checks should be performed for up to 24 hours following. – The same concern may not exist for placement of peripheral nerve blocks, as epidural hematoma is not a consideration.

EQUATIONS

• International sensitivity index (ISI) is determined for each reagent/instrument combination depending on the performing lab. • INR = (measured PT/control PT)ISI GRAPHS/FIGURES

Coagulation cascade

Bold arrows: factor conversion; Thin arrows: activation Dashed arrows: inhibition

REFERENCES

1. nsell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S. 2. ensley FA, Martin DE, Gravlee GP. Coagulation management during and after cardiopulmonary bypass. In A Practical Approach to Cardiac Anesthesia. Philadelphia, PA, 2008:497–498. 3. irsh J, Poller L. The international normalized ratio. A guide to understanding and correcting its problems. Arch Intern Med. 1994;154:282. 4. Horlocker T, Wedel D, Benzon H. Regional anesthesia in the anticoagulated patient: defining the risks (the second ASRA consensus conference on neuraxial anesthesia and anticoagulation). Reg Anesth Pain Med. 2003;(28):172–197. 5. Zehnder JL, Clinical Use of Coagulation Tests, UpToDate. Hirsch J, Fuster V, Ansell J, Halperin JL. AHA/ACC Scientific Statement: American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy. Circulation. 2005;107:1692–1711.

ADDITIONAL READING • www.asra.com

See Also (Topic, Algorithm, Electronic Media Element) • Prothrombin time (PT) • Partial thromboplastin time (PTT) • Cirrhosis • Protein C • End-stage liver disease • Epidural hematoma

CLINICAL PEARLS

• Whole blood should be collected in citrated anticoagulant at the specific ratio of one part citrate to nine parts blood. Most collection tubes have the correct fill level marked. • Polycythemic patients require a smaller amount of anticoagulant due to relatively lower volume of plasma in the sample. Lack of correction leads to artificially prolonged INR. • Sample should be free of tissue fluids, IV solutions delivered through indwelling catheters, and heparin. • The American College of Chest Physicians and National Heart, Lung, and Blood Institute suggested the following therapeutic ranges for warfarin therapy: – 2.0–3.0 for prevention of venous thromboembolism, treatment of deep venous thrombosis and pulmonary embolism, tissue heart valves, atrial fibrillation, and acute myocardial infarction – 2.5–3.5 for mechanical prosthetic valves

INTESTINAL OBSTRUCTION Suzanne Strom, MD

BASICS DESCRIPTION

• Patients with intestinal obstruction commonly present to the operating suite for exploratory laparotomy or laparoscopy. However, they are considered a “full stomach” and pose an increased risk when sedating or securing their airway. Hypoxia, respiratory failure, and ARDS can result if stomach and/or intestinal contents trespass into the trachea. EPIDEMIOLOGY Incidence

• Small bowel obstruction is the most common cause of intestinal obstruction and comprises 60–80% of all obstructions. • Perioperative aspiration. Despite the number of patients with “full stomach” and intestinal obstruction, the incidence in the general population may be as low as 0.05% because of provider vigilance. Morbidity

• Approximately one-quarter of patients having surgery for obstruction will have some complication. Rates increase when the patient has advanced age, comorbidities, a delay in treatment, or previous abdominal surgery. • Laparoscopic repair of lesions has decreased rates of morbidity and mortality.

Mortality

• Small bowel obstructions caused by adhesions carry a 5–10% risk of mortality. The risk rises significantly in patients with large bowel obstruction from malignancy or bowel gangrene, reaching 15–28%. • Mortality from aspiration alone can be anywhere from 3% to 70%. • Abdominal surgery that is complicated by aspiration pneumonitis has a mortality risk as high as 75%. ETIOLOGY/RISK FACTORS

• Intestinal obstructions are most often caused by: – Adhesions secondary to previous surgery – Inflammatory processes – Endometriosis • Risk factors for aspiration are – GI dysfunction. Abnormal lower esophageal sphincter (LES) function, abnormal esophageal motility, esophageal diverticulum or neoplasm, hiatal hernia, peptic ulcer, gastritis, abdominal distension, intestinal or gastric outlet obstruction, abdominal trauma,

gastroesophageal reflux disease (GERD) abdominal infection, recent meal, obesity, pregnancy, and presence of nasogastric (NG) tube (tube stents open the LES and prevents full closure while not completely emptying the stomach contents). – Airway dysfunction. Inadequate pharyngeal reflexes, weak cough, and recent extubation (dysfunctional vocal cords, poor muscular coordination of hypopharynx, residual sedation). – Comorbidities. Extremes of age, altered mental status, pain, emergency operation, upper abdominal or emergency abdominal surgery, and elevated intracranial pressure (ICP).

PATHOPHYSIOLOGY

• Third spacing. Patients with intestinal obstruction have considerable movement of intravascular volume into the interstitial space because of the inflammatory response to bowel distension and ischemia. It can result in significant hypovolemia. • Aspiration. The increase in abdominal pressure can result in aspiration of stomach/bowel contents when patients are sedated or during the period between induction and endotracheal intubation. – The three factors most important in determining the severity of a pulmonary insult in aspiration are the volume, pH, and amount of particulate matter. – The most severe pneumonitis can be caused with volumes >25 mL (or 0.3 mL/kg) and a pH <2.5. – Particulate matter can physically obstruct small airways and lead to ventilation/perfusion mismatch, hypoxia, hemorrhagic edema, and even acute pulmonary hypertension. • Pulmonary implications – Functional residual capacity (FRC) is decreased with abdominal distension, the supine position, and general anesthesia. Atelectasis results in an increased Alveolar-arterial gradient. – Impairment of normal diaphragmatic function and splinting from incisional pain can cause continued respiratory embarrassment postoperatively. This is worsened by residual anesthesia, IV anesthetics, and neuromuscular blockade. – Vital capacity remains abnormal for at least 1 week following upper abdominal surgery; aggressive pulmonary hygiene is encouraged.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Anticipate the possibility that bowel obstruction has an increased risk for pulmonary aspiration. Consider: – NG tube placement and suctioning prior to induction – Induction in the reverse Trendelenburg position – Rapid sequence induction with cricoid pressure – Suction equipment checked and ready – Ability to quickly reposition the patient into Trendelenburg should aspiration occur • Volume status should be assessed. Third spacing of fluids, vomiting, and NPO status can result in a relative intravascular hypovolemia. Induction on anesthesia can result in hemodynamic compromise or collapse.

PREOPERATIVE ASSESSMENT SYMPTOMS

Determine if the patient has had nausea and vomiting. History

Evaluate for NPO status, GERD, and other risk factors. Signs/Physical Exam

• Evaluate abdomen • Skin turgor, and mucous membranes for signs of hypovolemia.

TREATMENT HISTORY

• If the patient has had an NG tube placed, it is important to note its output. • The patient may have had oral contrast for imaging of the lesion, which can add to the increased gastric volume.

MEDICATIONS

Evaluate for the use of prokinetic agents, Histamine-2 (H2) blockers, proton-pump inhibitors,

as well as pain medicines.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Review electrolytes for expected derangements and acid–base disorders. • CBC should be ordered to evaluate for hemoconcentration. WBC should be followed since the patient is at risk for sepsis.

CONCOMITANT ORGAN DYSFUNCTION

Patients with obstruction often have poor nutrition, sepsis, hypovolemia, tachycardia, and hypotension. CIRCUMSTANCES TO DELAY/CONDITIONS

If the patient has not been adequately resuscitated (as evidenced by normalization of heart rate and BP, return of urine output, and normalization of hemoconcentration and BUN/Cr ratio), one should weigh the risks of proceeding with the benefits of fluid resuscitation prior to induction. CLASSIFICATIONS

Partial versus complete obstruction

TREATMENT PREOPERATIVE PREPARATION Premedications

• Volume resuscitation • Reduce acidity of gastric contents. Nonparticular, clear antacids such as sodium bicitrate increase the pH of fluids immediately while increasing gastric volume. However, they are associated with only mild pulmonary changes if aspirated. H2 blocking agents such as

famotidine are effective at reducing the acidity and can also mildly decrease gastric fluid volume (use may be limited due to onset time). By contrast, proton-pump inhibitors like protonix are effective more rapidly, but still need to be administered 1 hour prior to surgery. • Consider reducing gastric volume with NG tube placement.

Special Concerns for Informed Consent

The severity of the associated conditions and risk of morbidity should be addressed. INTRAOPERATIVE CARE Choice of Anesthesia

While it is possible to have adequate surgical exposure with neuraxial anesthesia, aspiration risk and the possibility of hemodynamic instability often necessitate general anesthesia with a cuffed endotracheal tube (also allows for positive pressure ventilation to compensate for decreased lung compliance) Monitors

• Standard ASA monitors should be used. • CVC or arterial line placement may be necessary if the patient is hemodynamically unstable.

Induction/Airway Management

• Goals include avoiding aspiration while maintaining hemodynamic stability. • Rapid sequence induction (RSI). Should proceed with cricoid pressure and rapid administration of sedative/hypnotic and neuromuscular blockade. Avoidance of mask ventilation can decrease insufflation of the stomach. Cricoid pressure (Sellick maneuver) should be applied and not released until the cuff is inflated and tube placement has been verified by capnography and auscultation. • Awake intubation should be considered in difficult airways (RSI is contraindicated).

Maintenance

• Choice of anesthetic is only limited by concerns about nitrous oxide (N2O) administration.

This may lead to increased intraluminal volume and pressure, which can cause bowel ischemia and difficulty with abdominal closure. Use should be avoided or minimized until closure of the abdominal fascia is complete. • Fluid resuscitation should continue in the intraoperative period. Additionally, there is the potential for significant insensible fluid losses and third spacing. • Monitor for electrolytes and acid–base status, as appropriate. • Ventilator settings. Increased peak inspiratory pressures may be seen with decreased pulmonary compliance from the underlying pathology as well as retractors and positioning. Consider adjusting volumes, respiratory rate, I:E ratios, and mode (volume versus pressure)

to optimize pressures and decrease the risk of barotrauma, hypoxia, or hypercarbia. Increases in atelectasis may be offset or decreased with PEEP. • Muscle relaxation should be administered and monitored to aid with exposure and closing. • Temperature. Large bowel incisions may present difficulty with maintaining normothermia. Ensure that patients are covered and warming techniques considered for the upper and lower body; fluids are warmed; irrigation is warmed; and consider warming the room.

Extubation/Emergence

• In any patient with known intestinal obstruction or “full stomach,” an attempt should also be made to suction the esophageal and gastric material before emergence from anesthesia. • In addition, extubation should occur only after swallowing, adequate strength, and the ability to follow commands has been clearly demonstrated. • Delayed awakening might occur due to metabolic causes. Patients with acidosis, hemodynamic instability, and ventilation/perfusion mismatch can result in failure to meet extubation criteria.

POSTOPERATIVE CARE BED ACUITY

Depending on the severity of the pathology, patients should be monitored appropriately. MEDICATIONS/LAB STUDIES/CONSULTS

• Analgesia – Postoperative opioids should be carefully administered to prevent excessive sedation and subsequent aspiration during recovery. – Placement of a regional or neuraxial block in the postoperative period can prevent splinting and sedation, as well as improve deep breathing techniques. Ensure that the patient has been properly resuscitated and does not have a coagulopathy. • Electrolytes and CBC as appropriate • Antibiotics as appropriate

COMPLICATIONS

• The most common concerns are – Aspiration pneumonia and respiratory failure – Cardiovascular instability from acidosis and hypovolemia.

REFERENCES

1. El-Orbany M, Connolly LA. Rapid sequence induction and intubation: Current controversy. Anesth Analg. 2010;110(5):1318–1325. 2. g A, Smith G. Gastroesophageal reflux and aspiration of gastric contents in anesthetic practice. Anesth Analg. 2001;93:494–513. 3. Olsson GL, Hallen B, Hambraeus-Jonzon K. Aspiration during anaesthesia: A computeraided study of 185,358 anaesthetics. Acta Anaesthesiol Scand. 1986;30:84. See Also (Topic, Algorithm, Electronic Media Element)

• Aspiration • Functional residual capacity • Intubation and extubation criteria

CODES ICD9

560.9 Unspecified (Intestinal obstruction) ICD10

K56.60 Unspecified intestinal obstruction

CLINICAL PEARLS

• The three factors most important in determining the severity of a pulmonary insult in aspiration are the volume, pH, and amount of particulate matter. • Unrecognized or “silent” regurgitation can occur, as well as subsequent aspiration that is subclinical.

INTRACRANIAL HYPERTENSION Shreyas Bhavsar, DO

BASICS DESCRIPTION

• Intracranial pressure (ICP) is the pressure exerted on the dura by the contents of the cranial vault; normal ICP is <15 mm Hg. • Intracranial hypertension (ICH) is a neurological emergency that, if left untreated, can cause brain herniation, irreversible neuronal damage, compromised cerebral blood flow (CBF), and eventually death. • Treatment includes medical management and possibly surgery (resection of the mass lesion or a decompressive craniectomy for cases refractory to medical management). These procedures are performed to improve brain tissue oxygenation and CBF. PHYSIOLOGY PRINCIPLES

• The cranium is comprised of – Brain matter – Cerebrospinal fluid (CSF) – Blood; both arterial and venous – A noncompliant intracranial vault with only a small reserve for additional volume (provided by the intervertebral spaces). • Monroe–Kellie hypothesis: The intracranial volume is in dynamic equilibrium; the increase in one component volume will cause a decrease in volume of the other components in order to prevent increases in ICP. • Cerebral perfusion pressure (CPP) = MAP–ICP, where MAP is mean arterial pressure and ICP is intracranial pressure – Normal cerebral autoregulation maintains CPP between 50 and 150 mm Hg (see Equation). – If the CPP is <50 mm Hg or >150 mm Hg, then CBF directly follows changes in perfusion pressure. – PaO2: Severe hypoxia causes cerebral vasodilation. A PaO2 <50 mm Hg drastically increases CBF. – PaCO2: CBF is directly proportional to changes in PaCO2. Between a PaCO2 of 20 and 80 mm Hg, blood flow changes ∼1–2 mL/100 g/min per mm Hg of PaCO2.

– Cerebral metabolic rate of oxygen (CMRO2): Cerebral metabolic activity is directly coupled to increases or decreases in CBF.

ANATOMY

• Intracranial volume is comprised of – Brain tissue: 80%

– CSF: 8–12% – Intracerebral blood • Radiological images of brain with high ICP will reveal a midline shift and effaced basal cisterns.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Once maximum capacitance is achieved, additional volume will quickly increase the ICP. • Anatomical factors that increase ICP – Brain tissue: Tumors, edema (ischemic stroke, cerebral contusion), trauma (epidural hematoma, subdural hematoma, cerebral contusion), psuedomotor cerebri – CSF: Hydrocephalus – Blood: Hypoxia, hypercarbia, obstruction of venous return from head position, Valsalva maneuvers or increased intrathoracic pressures (coughing, gagging, excessive PEEP), seizures, severe hypertension, hypotension (vasodilation to maintain CBF can increase cerebral blood volume)

PERIOPERATIVE RELEVANCE

• Clinical signs of increased ICP – Headache – Nausea/vomiting – Periodic or irregular breathing – Decreased mental status (obtunded, comatose) – Papilledema – Cushing response: Severe hypertension, bradycardia, and irregular respirations • This response indicates severe brain herniation. ICP leads to compression of intracerebral vessels and cerebral ischemia. Reflexively, the body activates hemostatic mechanisms to maintain cerebral perfusion by increasing the systemic BP (mainly systolic and hence widening the pulse pressure). Likely, the carotid baroreceptors sense the increased pressure and, in turn, activate the vagal response to slow the heart rate. • Perioperative goals include maintaining the CPP by: – Mean arterial pressure (MAP): Increase or maintain – ICP: Decrease or prevent increases • Monitors – Standard ASA monitors, with special attention to capnography – Arterial line for continuous BP monitoring and blood gas sampling (PaO2, PaCO2,

glucose). – Fluid intake and output with a Foley catheter and possibly a central venous catheter – Continuous ICP monitoring – Nerve stimulator to help determine depth of neuromuscular blockade – EEG may be needed during barbiturate coma to determine depth of sedation, evaluate for seizures, and to help establish cerebral electrical silence. • Induction and airway management – Head of bed (HOB) at 30°. Facilitates cerebral venous drainage and decreases intracerebral blood volume. However, it may hinder brain tissue oxygenation. – Intubation and controlled ventilation can facilitate (or avoid) hypoventilation.

– Rapid sequence intubation (RSI) should be used in emergent conditions. The benefits of quickly securing the airway and controlling respiratory parameters (avoiding hypoxia, hypercarbia) outweigh the small and transient increase in ICP from succinylcholine. However, if the patient is not adequately anesthetized or only partial muscle relaxation has occurred, ICP can increase during direct laryngoscopy and intubation. • Maintenance is typically via a combined technique to minimize any further increases in ICP. – Volatile anesthetics decrease CMRO2 in a dose-dependent manner, dilate cerebral blood vessels, and increase CBF (uncoupling). – Nitrous oxide causes mild cerebral vasodilation. Its effects are generally mild especially when used with other IV agents. – Propofol decreases CBF and CMRO2 and has some anticonvulsant properties.

– Opioids have little direct effect on CBF, CMRO2, and ICP. Respiratory depression may cause changes in PaCO2.

– Muscle relaxation has no direct effect on the brain. – Succinylcholine can potentially increase ICP but that effect can be attenuated with a defasciculating dose of a nondepolarizing neuromuscular blocker and adequate induction agent. – Head flexion and rotation can impede venous outflow from the brain and should be avoided. – Hyperventilation: Adjusting the PaCO2 to 30–35 mm Hg is one of the fastest techniques to decrease ICP. Decreases in the PaCO2 alkalinize the CSF and cause cerebral

vasoconstriction. This phenomenon, however, fades with time as the CSF readjusts to a normal pH (vasoconstrictive effects typically last 11–20 hours). Avoid excessive hyperventilation (PaCO2 <25 mm Hg), as it can contribute to cerebral ischemia.

– Maintain a CPP >60 mm Hg. With increased ICP, cerebral perfusion is maintained by systemic hypertension and sympathetic hyperactivity. To that extent, caution is advised in treating hypertension as it may result in cerebral ischemia (hypotension is an independent risk factor for poor outcomes). At the same time, the risk of persistent systemic hypertension includes cerebral edema and intracranial hemorrhage. Furthermore, cerebral autoregulation can be compromised in areas of brain injury and complicates the management of systemic hypertension. If treatment is undertaken, short-acting titratable drugs (beta-blockers, propofol) can be used to lower the BP and avoid increases in ICP. Avoid drugs such as nifedipine, nitroglycerine, or nitroprusside as they can induce cerebral vasodilation and worsen ICP. – Mannitol is a hyperosmolar agent that is commonly used to lower ICP (effect is dosedependent). IV bolus doses of 0.25–1 g/kg can begin to decrease the ICP in 1–5 minutes (peak effect of 20–60 minutes, duration up to 6 hours). Redosing may be required for continued clinical effect. Advantages include its free radical scavenging properties and reduction in CSF production. Adverse effects include hypotension (initial vasodilatory response), exacerbation of congestive heart failure (initial intravascular osmotic effect), electrolyte abnormalities (later diuresis), and cerebral edema (areas of compromised blood-brain barrier, or rebound from prolonged administration). Mannitol is, thus,

contraindicated in hypovolemic and hypotensive patients. – Hypertonic saline creates an osmotic gradient for interstitial intracerebral fluid to shift intravascularly. This reduces overall brain volume and decreases ICP. This has a more pronounced effect compared to mannitol and can be used in a hypovolemic and/or hypotensive patient needing intravascular volume expansion. Potential adverse effects include hyperchloremic metabolic acidosis, platelet dysfunction, prolonged coagulation parameters, and central pontine myelinolysis. – Furosemide: A loop diuretic that may decrease the production of CSF; less effective than hypertonic saline and mannitol. – Sedation and analgesia: Pain and agitation can increase ICP and should be addressed. Benzodiazepines can decrease CMRO2 and CBF without effects on the ICP; beware of

hypotension or hypercarbia. – Avoid seizures: Consider antiepileptics to avoid significant increases in CMRO2, CBF, and

ICP. – Avoid hyperglycemia: Associated with poor neurological outcomes. The optimal target glucose range is uncertain but generally maintained below 220 mg/dL. – Corticosteroids decrease vasogenic edema from primary and metastatic tumors; a common regimen is dexamethasone 4 mg IV every 6 hours. Steroids can increase serum glucose levels and if left uncontrolled can lead to hyperglycemia. – Barbiturate coma has not been shown to improve outcomes but can be considered in refractory, elevated ICP. Proposed mechanisms: a coupled reduction in CBF with decreased CMRO2 and arterial vasoconstriction (decreases CBF). Disadvantages include the loss of neurological exam and hypotension. – CSF drainage: Removal of CSF is a quick and reliable method to lower the ICP. The most common method is through a ventriculostomy that has the advantage of being both a therapeutic and diagnostic maneuver. Disadvantages include a risk of infection, hemorrhage, and difficulty in placement with diffuse cerebral edema or slit-like ventricles. Fiberoptic monitoring devices can be placed in the subarachnoid space, epidural space, or brain parenchyma. They are easier to place but cannot remove volume and cannot be recalibrated. An external ventricular device can be placed for temporary measures, while ventricular shunts are placed for chronic ICP management (i.e., hydrocephalus). – Avoid hyperthermia: Increases in temperature can elevate the CMRO2 and hence CBF.

Outcome studies have demonstrated worsened neurologic injury in traumatic brain injury. Treatment includes antipyretics, cooling blankets, and treatment of infectious causes. – Hypothermia: Controversial with no studies showing improved neurological outcomes. It may be considered in cases of severe refractory ICH maximized on medical management. • Extubation and emergence – Extubation criteria are the same as with any surgical procedure (confirm that neurological issues are stable or resolved); if extubation is not possible, consider appropriate sedation. Avoid bucking/straining/coughing that can worsen ICP or cause cerebral hemorrhage. Consider IV lidocaine to attenuate the gag reflex to suctioning/extubation. Rapid awakening is also important to conduct a neurological assessment postoperatively.

EQUATION

CPP = MAP - ICP; where CPP is cerebral perfusion pressure, MAP is mean arterial pressure, and ICP is intracranial pressure. GRAPHS/FIGURES

FIGURE 1. Increases in intracranial volume begin to increase the intracranial pressure within the fixed/rigid cranial vault after compensatory mechanisms have been exhausted.

REFERENCE

1. ershad EM, Humphreis WE, Suarez JI. Intracranial hypertension. Semin Neurol. 2008;28(5):690–702. 2. Jantzen JP. Prevention and treatment of intracranial hypertension. Best Pract Res Clin Anaesthesiol. 2007;21(4):517–538. 3. Rangel-Castilla L, Gopinath S, Robertson CS. Management of intracranial hypertension. Neurol Clin. 2008;26(2):521–541. 4. Wolfe TJ, Torbey MT. Management of intracranial pressure. Curr Neurol Neurosci Rep. 2009;9(6):477–485. See Also (Topic, Algorithm, Electronic Media Element) • Cerebral blood flow • Cerebral metabolic rate • Circulatory arrest • Burst suppression

CODES ICD9 348.2 Benign intracranial hypertension ICD10 G93.2 Benign intracranial hypertension

CLINICAL PEARLS

• Treatment of ICH includes medical and surgical means.

• Medical treatment – HOB at 30° – Secure airway and ensure normal oxygenation (PaO2 >60 mm Hg) – Hyperventilate to a PaCO2 of 30–35 mm Hg

– Maintain CPP >60 mm Hg – Mannitol 0.5–1.0 g/kg IV bolus – Consider hypertonic saline, antiepileptics, steroids, barbiturate coma – Diuretics – Avoid factors that aggravate ICP • Surgical treatment is often undertaken if the ICP increases suddenly or is refractory to medical management. – CSF drainage via ventriculostomy – Decompressive craniectomy

INTRAOPERATIVE MYOCARDIAL ISCHEMIA Alan P. Zaggy, MD

BASICS DESCRIPTION

• Intraoperative myocardial ischemia can occur when there is an oxygen supply and demand imbalance. This can lead to such perioperative events as: – Congestive heart failure (CHF) – Arrhythmias – Myocardial infarction (MI) – Cardiogenic shock and end-organ damage – Death • A thorough preoperative cardiac evaluation can identify the severity (and presence) of disease in patients with diagnosed or suspected coronary artery disease (CAD). History and physical exam, combined with laboratory, EKG, and stress testing (stress EKG, echocardiography, nuclear scans), can confirm or refute myocardium at risk for ischemia. EPIDEMIOLOGY Incidence

• CAD, the primary contributing factor to myocardial ischemia, affects over 11 million Americans. • The incidence of perioperative myocardial ischemia is unknown as its detection is largely a function of monitoring technique (simple or multilead EKGs with or without computer ST segment analytic enhancement, pulmonary artery catheter, TEE, etc.) and the skill of the monitoring personnel. Prevalence

CAD in the general population increases with age. • Age 15–44 years: 4 per 1,000 • Age >65 years: 80 per 1,000

Morbidity

Myocardial ischemia can lead to infarction, arrhythmias, heart failure. Mortality

Perioperative MI remains the leading cause of postoperative death in the elderly (1)[C]. ETIOLOGY/RISK FACTORS • Preoperative risk factors: – Increasing age – Previous MI

– Angina – Arrhythmias – Hypertension – Diabetes mellitus – Peripheral vascular disease – Hypercholesterolemia – Cigarette smoking • Perioperative risk factors: – Hypertension – Hypotension – Hypoxia – Hemodilution – Tachycardia – Increased cardiac work/tension

PHYSIOLOGY/PATHOPHYSIOLOGY

• Ischemia can result from a decrease in oxygen supply or an increase in oxygen demand. • Decreased myocardial oxygen supply is the result of a decrease in coronary blood flow or blood oxygen content: – Decreased coronary artery perfusion pressure can result from decreased diastolic blood pressure or increased left ventricular end-diastolic pressure. CPP = DBP - LVEDP, where CPP is coronary perfusion pressure, DBP is diastolic blood pressure, and LVEDP is left ventricular end-diastolic pressure. – Coronary artery stenosis (fixed) or vasospasm (variable) obstructs coronary blood flow. Distal to the stenosis, the vessel becomes maximally dilated over time to maintain blood flow. However, it lacks the ability to further compensate for decreases in blood flow. – Thromboembolic phenomenon. Stasis, inflammation, and tachycardia can dislodge clots and block coronary arteries, decreasing coronary blood flow. – Tachycardia decreases diastolic time, and, thus, the duration that the LV is perfused. During systole, LV intracardiac pressures exceed CPP; thus, blood flow only occurs during diastole. – Decreased blood oxygen-carrying capacity can result from red blood cell loss/anemia, decreased oxygen saturation, or hypoxemia. • Increased myocardial oxygen demand occurs when there is an increase in cardiac work: – Tachycardia increases the number of times that the myocardium depolarizes and repolarizes as well as mechanically contracts and relaxes. – Increased contractility. Mechanical contraction follows myocyte depolarization and involves the energy consuming process of sarcomere shortening. – Increased ventricular wall tension can occur with Increased afterload (pressure work): Increased systemic (or pulmonary) vascular resistance, intraventricular pressures and radius, as well as hyperviscosity, and decreased aortic compliance Increased preload (volume work) – Ventricular hypertrophy. The increased muscle mass requires a greater amount of energy for each contraction. Additionally, the “watershed” subendocardium is more likely to

become ischemic during times of decreased supply or increased demand.

PREVENTATIVE MEASURES

• Optimize myocardial oxygen supply – Maintain mean arterial pressures. General anesthesia with volatile or IV medications as well as neuraxial blocks can decrease BP. Consider the use of nitrous oxide to allow decreased doses, low-dose vasopressor infusions, and fluid and/or blood administration, as appropriate. – Decrease LVEDP. Consider enhancing inotropy to improve emptying as well as decreasing preload – Decrease the risk for thromboembolic phenomenon. Discuss with the surgeon and primary care doctor/cardiologist the perioperative management of platelet inhibitors or other anticoagulants in patients currently on medications or at high-risk for cardiac events. The pleiotropic effects of statins have been shown to improve endothelial function, enhance the stability of atherosclerotic plaques, decrease oxidative stress and inflammation, and inhibit the thrombogenic response. Certain patient populations may benefit from de novo preoperative administration; additionally, abrupt withdrawal in patients taking statins has been associated with an increase in myocardial events. – Decrease the heart rate with beta-blockers, calcium channel blockers, and opioids. Additionally, avoid increases in heart rate from drugs with sympathetic or vagolytic properties as well as hypotension (reflex). Anticipate increases during laryngoscopy, incision, surgical stimulation, and extubation. – Optimize blood oxygen content with adequate hemoglobin levels and oxygen partial pressure. Consider transfusing blood, increasing the FIO2, adjusting ventilator settings

(respiratory rate, tidal volumes), and administering positive end-expiratory pressure (PEEP). • Decrease myocardial oxygen demand – As above, decrease the heart rate and anticipate inciting medications or events that can cause tachycardia. – Decrease inotropy, if appropriate, by removing sympathetic stimulation, administering beta-blockers, and avoiding drugs with positive inotropy. However, decreases in ejection fraction/stroke volume can increase the LVEDP (thus decreasing the CPP) as well as forward flow. – Decrease preload. Consider diuretics, venodilators, fluid restriction, and enhancing forward flow with inotropy, as appropriate. – Decrease afterload. Maneuvers to decrease systemic vascular resistance may jeopardize the mean arterial pressure and should be done cautiously.

DIAGNOSIS • Vital signs: Tachycardia, hypotension, hypertension, cardiac arrest • EKG. The standard lead monitoring (3 lead: I, II, III) is relatively insensitive, but can be altered by placing the left shoulder lead at the cardiac apex yielding a 3 lead: I, II, modified

V5 that allows for ischemic monitoring of the inferior (II) and lateral (V5) LV walls (the areas most vulnerable to ischemia). Diagnostic mode with computer ST segment analytic enhancement is more robust when used with a 5 lead system. Intraoperative 12-lead EKG is generally cumbersome and impractical. However, it may be considered when ischemia is suspected. – ST segment depression or elevation – T wave changes – Arrhythmias – Conduction changes • Pulmonary artery catheters may demonstrate increases in LVEDP or PCWP, reflecting a change in ventricular compliance during ischemic states, or acute mitral insufficiency from papillary muscle ischemia. The etiology of these changes should be determined to distinguish them from false positives. Additionally, decreases in cardiac output and mixed venous oxygen saturation can also suggest ischemia. • Transesophageal echocardiogram (TEE). New regional wall-motion hypokinesis, dyskinesis; systolic thinning/thickening abnormalities; new papillary muscle dysfunction/mitral insufficiency.

DIFFERENTIAL DIAGNOSIS

• False positive ST-segment changes may result from – Mitral valve prolapse – Pressure overload of the LV in young hypertensive patients can lead to false positive STsegment changes (2)[B]. – Left bundle branch block – Wolff–Parkinson–White syndrome – Right bundle branch block – Digitalis, tricyclic antidepressants, diuretics – Artificial pacemakers • Arrhythmias may be seen with sympathetic agents, metabolic abnormalities, drug toxicities

TREATMENT • Many of the treatment maneuvers are similar to preventative actions, but can differ in the degree of aggressiveness, level of invasive monitoring, as well as the possible need for discontinuing the surgery and intraoperative or postoperative cardiology evaluation. Additionally, because the heart is the pump for its own blood supply, decreasing oxygen consumption may come at the cost of decreasing the oxygen supply; this requires careful titration and optimization. • Decrease the heart rate with beta-blockers and remove inciting stimuli in order to increase oxygen supply and decrease demand. Beta-blockers need to be titrated appropriately to avoid undesired decreases in inotropy. • Decrease inotropy with myocardial depressants (beta-blockers, volatile anesthetics) in order to decrease myocardial work (3)[B] while maintaining an appropriate forward flow/stroke volume.

• Optimize the BP to balance coronary perfusion with myocardial tension (afterload). – Mean arterial pressures can be increased with vasopressors (alpha-agonists such as phenylephrine, norepinephrine, or vasopressin). High-dose dopamine and epinephrine have predominantly alpha-effects, but may be accompanied by tachycardia. Consider removing medications that decrease the systemic vascular resistance (e.g., volatiles, IV medications, and epidural infusions). – Decrease afterload with nitrovasodilators, volatile agents, calcium channel blockers. • Decrease preload with venodilators such as nitroglycerin (immediate) or diuretics such as furosemide (onset 20–30 minutes). Additionally, decreasing the LVEDV/LVEDP can optimize the CPP. • Increase blood oxygen content – Blood transfusion can increase the hemoglobin level, but is associated with metabolic abnormalities, immune reactions, increased viscosity, and worsened outcomes in critically ill patients. – Increase oxygen delivery – Optimize ventilation/perfusion (tidal volumes, respiratory rate, PEE) • Discontinue or abbreviate the surgical procedure, if appropriate. • Cardiology evaluation may be performed intraoperatively or in the recovery room.

FOLLOW-UP • EKG. Attain a 12-lead EKG and place the patient on continuous monitoring. • Cardiac enzymes should be drawn to evaluate for myocardial damage. Troponin (most cardiac-specific peaks at 12 hours), CK-MB (relatively cardiac-specific peaks at 10–24 hours), LDH (least cardiac-specific peaks at 72 hours). • Cardiology consultation to oversee dynamic cardiac stress or angiographic evaluation, acute interventional management (4)[A] (5)[B], and ongoing risk factors (6)[A].

REFERENCES

1. Djokovic JL, Hendley-Whyte J. Prediction of outcome of surgery and anesthesia in patients over 80. JAMA. 1979;242:2301. 2. roelicher VF, Yanowitz FG, Thompson AJ, et al. The correlation of coronary angiography and the electrocardiographic response to maximal treadmill testing in 76 asymptomatic men. Circulation. 1973;48:597. 3. emmotsu S, Hashimoto Y, Shimosato S. Inotropic effects of isoflurane on mechanics of contraction in isolated cat papillary muscles from normal and failing hearts. Anesthesiology. 1973;39:470. 4. Singh S, Bahekar A, Molnar J, et al. Adjunctive low molecular weight heparin during fibrinolytic therapy in acute ST-segment elevation myocardial infarction: A meta-analysis of randomized control trials. Clin Cardiol. 2009;32:358–364. 5. Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: Randomized placebo-controlled trial. Lancet. 2005;366:1622–1632.

6. Russell CL, Conn VS, Jantarakupt P. Older adult medication compliance: Integrated review of randomized controlled trials. Am J Health Behav. 2006;30:636–650. See Also (Topic, Algorithm, Electronic Media Element) • 12 Lead EKG • Coronary artery disease • Perioperative statins

CODES ICD9

414.8 Other specified forms of chronic ischemic heart disease ICD10 I25.89 Other forms of chronic ischemic heart disease

CLINICAL PEARLS

• Largely preventable with diligent hemodynamic monitoring and close attention to maintaining baseline hemodynamics and physiologic conditions in the face of surgical interventions. • Accurate EKG lead placement – especially leads II, V5 – is a cornerstone of myocardial ischemia detection. • Treatment should consist largely of restoration of baseline hemodynamic and physiologic conditions.

INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAM (TEE) Nanhi Mitter, MD Mary Brady, MD, FASE

BASICS DESCRIPTION

• TEE was first developed by cardiologists in the 1970s. It was used as a tool to measure left ventricular performance. • An M-mode transthoracic probe was originally used for epicardial imaging in patients undergoing coronary artery bypass grafting (CABG). Disadvantages of this included: – Interruptions in the surgery because it was manipulated by the surgeons – An inability to reproduce the images. • The first TEE probe was made of a wire and a vinyl esophageal stethoscope catheter. Modifications have continued; now probes are capable of: – Doppler technology, including color flow Doppler (CFD) – M-mode, 2D, and 3D • The National Board of Echocardiography provides two main types of perioperative TEE certification: – Advanced certification (since 2004) – Basic certification (since 2009) PHYSIOLOGY PRINCIPLES

• Doppler technology provides measurement of the velocity of red blood cells traveling within the heart. • The simplified Bernoulli equation provides an estimation of the pressure gradient between 2 chambers of the heart. This equation utilizes the velocity measured by Doppler technology. Δp = 4 (v2) – Specifically, the simplified Bernoulli equation can be used to estimate the right ventricle systolic pressure (RVSP) by measuring the velocity of the tricuspid regurgitation jet: RSVP (PASP) = 4vTR2 + RAP; were PASP is pulmonary artery systolic pressure and RAP

is right atrial pressure. – Another example of the utility of the simplified Bernoulli equation is in the evaluation of the gradient across a potentially stenotic AV. The pressure gradient between the LVOT and the AV can be estimated by measuring the velocity in the aorta. – Color Doppler technology provides estimation of blood flow direction. Blood flowing toward the transducer is depicted as red; blood flowing away from the transducer is depicted as blue. – BART: This mnemonic helps to remember the direction of blood flow in relation to the TEE probe: Blue Away, Red Towards

ANATOMY

A comprehensive examination can be performed based on the images outlined by Shanewise et al. These 20 images will allow a complete intraoperative examination. If adequate time is not available for a complete examination (i.e., in emergency situations), an abbreviated examination can be performed in order to obtain information from the 8 images listed below.

DISEASE/PATHOPHYSIOLOGY

• Chamber dimension: Abnormal chamber size can be associated with pathologic conditions. For example, increased left atrial size is seen in severe mitral regurgitation. • LV function: There are many measurements of LV function including Simpson’s method of discs, stroke volume, fractional area change, strain technology and tissue Doppler velocity. One of the simplest ways to determine a rough estimate of EF is by estimating endocardial thickening and excursion in the transgastric (TG), left ventricle (LV), midpapillary, sagittal views (SAX). This view is also helpful in evaluating ischemia as it represents perfusion from the 3 main coronary arteries. • Volume status: Gross LV filling can be estimated by using end-diastolic LV chamber size most often evaluated at the TG LV mid pap SAX view. • Valvular evaluation: A complete evaluation requires baseline knowledge of normal valve anatomy so as to diagnose abnormal anatomy by 2D Echo. This is corroborated with Doppler (CFD or Spectral) across the valve. Utilization of 2D echo and Doppler technology allows a detailed examination to evaluate the following (structure and function) in a native and/or prosthetic valve (e.g., the presence/absence of normal washing jets or abnormal perivalvular leaks).

• Aortic evaluation: The evaluation of the aorta should include interrogation for plaque, dissection, aneurysms, and thrombus from the root to the descending thoracic aorta (with the exception of the distal ascending and arch which cannot be imaged well due to interposition of left main stem bronchus as air prevents ultrasound penetration at that site). • Additional utility: Pleural effusions, pericardial effusions, and intracardiac masses can also be evaluated. Central venous pressure can also be estimated using the IVC diameter (ratio between inspiration and expiration). Specific signs of tamponade physiology from pericardial effusion include RA diastolic collapse and decreased RV filling. • Congenital: TEE is an invaluable tool in imaging cardiac anatomy in adult patients after complex congenital reconstruction who may be presenting for cardiac surgery as an adult. PERIOPERATIVE RELEVANCE

According to the 2010 ASA/SCA Guidelines, the indications can be classified by setting:

• Cardiac – “For adult patients without contraindications, TEE should be used in all open heart (e.g., valvular procedures) and thoracic aortic surgical procedures and should be considered in coronary artery bypass graft surgeries.” • Noncardiac – “TEE may be used when the nature of the planned surgery or the patient’s known or suspected cardiovascular pathology might result in severe hemodynamic, pulmonary, or neurologic compromise.” – “If equipment and expertise are available, TEE should be used when unexplained lifethreatening circulatory instability persists despite corrective therapy.” • ICU – “For critical care patients, TEE should be used when diagnostic information that is expected to alter management cannot be obtained by transthoracic echocardiography or other modalities in a timely manner.” – Three causes of hypotension that TEE is useful to manage: Hypovolemia Ischemia (best view: TG LV mid pap SAX) Tamponade – Regional wall abnormalities can be assessed: Normal: >30% Hypokinetic: <30% Akinetic: No movement Dyskinetic: Paradoxical systolic movement • Contraindications (ultimately, these are based on one’s clinical judgment) – Absolute Previous esophageal surgery Stricture Tracheoesophageal fistula Esophageal trauma Zenker’s diverticulum Colonic interposition

– Relative Barrett’s esophagus Hiatal hernia Large descending aortic aneurysm Unilateral vocal cord paralysis Esophageal varices Postradiation therapy Previous bariatric surgery • Complications are rare, but include: – Esophageal perforation – Esophageal injury – Hematoma – Laryngeal palsy – Dysphagia – Dental injury – Death • Artifacts – There are many types of well-known ultrasound artifacts. The details of these can be found in the references.

REFERENCES

1. Cheitlin MD, Armstrong WF, Aurigemma GP, et al. ACC/AHA/ASE 2003 guideline update for the clinical application for echocardiography: Summary article: A report of the American College of Cardiology/American Heart Association task force on practice guidelines (ACC/AHA/ASE committee to update the 1997 guidelines for clinical application of echocardiography). J Am Coll Cardiol. 2003;42:954–970. 2. Hilberath JN, Oakes DA, Shernan, et al. Safety of Tranesophageal Echocardiography. J Am Soc Echocardiogr. 2010;23:1115–1127. 3. Nishimura RA, Miller FA Jr, Callahan MJ, et al. Doppler echocardiography: Theory, instrumentation, technique, and application. Mayo Clin Proc. 1985;60(5):321–343. 4. Oka Y. The evolution of intraoperative transesophageal echocardiography. Mt Sinai J Med. 2002;69:18–20. 5. Quiñones MA, Otto CM, Stoddard M, et al. Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography Recommendations for quantification of Doppler echocardiography: A report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr. 2002;15(2):167–184.

6. Shanewise JS, Cheung AT, Aronson S, et al. ASE/SCA Guidelines for performing a comprehensive intraoperative multi-plane transesophageal echocardiography examination: Recommendations of the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists task force for certification in perioperative transesophageal echocardiography. Anesth Analg. 1999;89:870–884.

7. Thys DM, Abel MD, Brooker RF, et al. Practice Guidelines for Perioperative TEE: An Updated Report by the American Society of Anesthesiologists (ASA) and the Society of Cardiovascular Anesthesiologists (SCA) Task Force on TEE. Anesthesiology. 2010;112:1084– 1096. 8. www.echoboards.org See Also (Topic, Algorithm, Electronic Media Element) • Aortic stenosis • Pericardial tamponade

CLINICAL PEARLS

• It is important to note that the ASA/SCA perioperative guidelines specifically state that “proficiency…is of paramount importance due to risk of adverse outcomes resulting from incorrect interpretation.”

INTRARENAL ACUTE KIDNEY INJURY Andaleeb Abrar Ahmed, MBBS, MD, MPH Jill Eckert, DO

BASICS DESCRIPTION

• Acute renal failure (ARF), also known as acute kidney injury (AKI), is a common syndrome characterized by a rapid decline in glomerular filtration rate (GFR), accompanied by azotemia with, or without, oliguria. It is divided into three categories: – Prerenal. Impaired blood flow to the kidney – Intrarenal. Disease processes involving renal parenchymal tissue (may also result from prerenal causes). – Postrenal. Impaired movement of urine out of the kidneys. • Prevention and management of intrarenal ARF involves careful preoperative assessment, avoidance of nephrotoxic agents, maintenance of normovolemia, and close perioperative monitoring. EPIDEMIOLOGY Prevalence

• 1% of all patients undergoing general surgery develop postoperative AKI. • 1%–7% of patients with perioperative AKI require renal replacement therapy. • 35–40% cases of AKI can be attributed to intrarenal causes.

Prevalence

• 5–7% of hospital admissions and 30% of intensive care unit (ICU) admissions carry a diagnosis of AKI. • Acute tubular necrosis (ATN) accounts for 85% of intrinsic AKI. • Contrast-induced nephropathy (CIN) is the 3rd most common cause of AKI in hospitalized patients.

Morbidity

AKI is also associated with prolonged length of hospital stay and increased healthcare cost (1). Mortality

• Postoperative AKI worsens long-term survival in patients with normal baseline renal function (1). • AKI after noncardiac surgery is an independent predictor of hospital mortality. • AKI in the critical care setting has a mortality of 50% or higher.

ETIOLOGY/RISK FACTORS

• Causes of intrinsic AKI can be conceptually divided into four categories – Acute tubular necrosis Ischemia from hypotension or shock Nephrotoxic agents. Exogenous agents including NSAIDs, radiocontrast agents, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, antimicrobials such as aminoglycosides, amphotericin B, antiretrovirals. Endogenous agents such as rhabdomyolysis. – Tubulointerstitial disease Allergic interstitial nephritis (AIN) from antimicrobials (penicillin, cephalosporin, sulphonamide), NSAIDS, proton pump inhibitors, anticonvulsants (phenytoin, valproate) Infection (bilateral pyelonephritis) Infiltration (leukemia, sarcoidosis, lymphoma, myeloma, uric acid) – Diseases of large renal vessels Renal artery obstruction (atherosclerotic plaque, thrombosis, emboli, vasculitis, cholesterol embolization) Renal vein thrombosis, or compression – Diseases of the glomeruli and microcirculation Glomerulonephritis Vasculitis, collagen vascular disease Microangiopathic disorder (hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, preeclampsia) Malignant hypertension (HTN) • Patient risk factors include – Comorbidities (heart failure, liver failure, diabetes, chronic kidney disease) – Advanced age – Sepsis – Preoperative renal insufficiency – Prolonged hypovolemia – High ASA score status (3,4) • Surgical/procedure related factors include – Emergent surgery – Intra-abdominal surgery – Cardiac surgery – Vascular surgery – Aortic cross-clamping or occlusion of the inferior vena cava (IVC) – Intra-aortic balloon counterpulsation – Organ transplantation

PHYSIOLOGY/PATHOPHYSIOLOGY

• Three-phase sequence – Initiation: Characterized by an acute decrease in GFR and increase in creatinine (Cr) and BUN. – Maintenance: Demonstrates a sustained severe reduction in GFR; variable length of time (1–2 weeks); BUN and Cr continue to rise. – Recovery: Characterized by an increase in urine volume and by a gradual decrease in

BUN, Cr to preinjury levels. • GFR. An acute decline in GFR is a hallmark of AKI. Proposed mechanisms include – Reduced glomerular filtration pressure due to renal autoregulatory disruption. – Back-leak of glomerular filtrate due to disruption of normal tubular epithelium. – Luminal obstruction due to epithelial cell sloughing. • Histopathology. Microvascular inflammation, apoptosis, and endothelial cell dysfunction play a major role in the pathophysiology of AKI. Proximal tubular epithelium demonstrates obliteration from necrotic cells that lack a nucleus. However, the basement membrane remains intact, so tubular epithelium regeneration is possible.

PREVENTATIVE MEASURES

• Any anesthetic technique causing a reduction in BP will decrease GFR, renal blood flow, and urine formation. Carefully titrated neuraxial anesthesia that achieves a sympathetic block to the T4 to T10 level may be beneficial in diminishing the renal vasoconstrictive response from sympathoadrenal stimulation. However, hypotension secondary to neuraxial anesthesia may impair renal perfusion. • Except for aiding diuresis, loop diuretics, and mannitol have no role in preventing or treating ARF. • Whenever possible, low or iso-osmolar, nonionic contrast media should be considered.

PREOPERATIVE ASSESSMENT • History – ATN: Exposure to nephrotoxic agents; recent surgery, hemorrhage, or hypotension; history of chronic renal insufficiency; evidence of sepsis, or pyelonephritis; history suggestive of rhabdomyolysis (trauma, drug abuse, seizure, urine color), tumor lysis syndrome (recent chemotherapy), myeloma (bone pain), or hemolysis (recent blood transfusion). – AIN: Recent drug use, fever, rash, or arthralgia. – Malignant HTN: Headache, neurological dysfunction, heart failure, papilledema. – Atheroembolism: Vascular procedure, atrial fibrillation, thrombolysis, or anticoagulation. – Glomerulonephritis/vasculitis: Edema, sinusitis, hematuria, hemoptysis, HTN, recent infection, and rash. • Symptoms are usually absent, mild, or nonspecific in the early stages of ARF. • Urine analyses (U/A) – Muddy brown casts and tubular epithelial cells: ATN – White cell casts/eosinophiluria: Pyelonephritis, interstitial nephritis, cholesterol emboli – Red blood cell (RBC) casts: Glomerulonephritis – Crystalluria: Drug toxicity, tumor lysis syndrome – Brown waxy casts: Chronic renal failure – Bacteria: Pyelonephritis – Proteinuria: Glomerulonephritis, thrombotic microangiopathy, cholesterol emboli, nephrotic syndrome, vasculitis, AIN, malignant HTN, and renal vein/artery thrombosis. – Hematuria: Glomerulonephritis, renal vein/artery thromboses, vasculitis. • Serum creatinine (Cr), BUN, urine indices – Serum BUN/Cr ratio >20:1, likely prerenal; <20:1, likely ATN (4).

– Urine sodium (mEq/L): <20, likely prerenal; >40 likely ATN (4) – Fractional excretion of sodium (FENa) (%): FENa = [(UNa × PCr)/(PNa × UCr)] × 100, where U = urine, P = plasma, Na = sodium, Cr = creatinine. If FENa <1%, likely prerenal; if FENa >2%, likely intrarenal (4)

– Fractional excretion of urea (FEurea) (%): FEurea = [(Uurea × PCr)/(PBUN × UCr) × 100. FEurea <35% is suggestive of prerenal etiology.

– Urine osmolality (mOsmol/kg): >500, likely to be prerenal; <400, likely ATN (4). – Urine/Plasma creatinine (UCr/PCr): >40, likely prerenal; <20, likely ATN.

• Assessment of GFR – Creatinine clearance (ml/min) is commonly used to estimate GFR. – Creatinine clearance = (UCr × Uv)/PCr, × 1440, where Uv is 24-hour urine volume in mL. – GFR is estimated using the Modification of Diet in Renal Disease (MDRD), or Cockcroft– Gaut equation. • Renal ultrasound: To assess kidney size, renal parenchyma and rule out urinary obstruction • Serum electrolytes, arterial blood gas (ABG), CBC, EKG

DIFFERENTIAL DIAGNOSIS

• Prerenal acute kidney failure • Postrenal acute kidney failure

TREATMENT • Nephrology consultation may be needed for management of dyselectrolytemia, severe azotemia, or refractory volume overload. Hemodialysis (HD), continuous renal replacement therapy, and ultrafiltration may be considered. • Early goal-directed resuscitation for sepsis • Protein restricted, low potassium diet • CIN: N acetyl cysteine (600 mg PO BID), IV NaHCO3 • Metabolic acidosis: Bicarbonate • Malignant HTN and preeclampsia: BP control • Uremic bleeding: Desmopressin • “Renal dose” dopamine and fenoldopam is unlikely to be beneficial.

FOLLOW-UP • Complications of ARF include death, arrhythmias, volume overload, hyperkalemia, metabolic acidosis, infection, pericarditis, platelet dysfunction, bleeding, anemia, and longterm renal replacement therapy. • ICU may be required for closer hemodynamic monitoring.

REFERENCES

1. orthwick E, Ferguson A. Perioperative acute kidney injury: Risk factors, recognition, management, and outcomes. BMJ. 2010;341:c3365. 2. ehta RL, Kellum JA, Shah SV, et al. Acute kidney injury network: Report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31.

3. Bentley ML, Corwin HL, Dasta J. Drug-induced acute kidney injury in the critically ill adult: Recognition and prevention strategies. Crit Care Med. 2010;38(6 Suppl):S169–174. 4. Esson ML, Schrier RW. Diagnosis and treatment of acute tubular necrosis. Ann Intern Med. 2002;137(9):744–752. See Also (Topic, Algorithm, Electronic Media Element) • Prerenal acute kidney failure • Postrenal acute kidney failure

CODES ICD9 584.9 Acute kidney failure, unspecified ICD10 N17.9 Acute kidney failure, unspecified

CLINICAL PEARLS

Patients with ARF should have nonemergent surgery delayed until improvement has occurred. If necessary to proceed: • Nephrotoxic drug exposure should be avoided in the perioperative period (e.g., aminoglycosides and ketorolac). • Volume status. Maintain normal volume status and consider placement of invasive monitors to aid with management (e.g., arterial line, central line, or pulmonary artery catheter). Diuretics should be avoided until adequate intravascular volume has been achieved. • Renally cleared drugs can have a prolonged duration of action (e.g., benzodiazepines). Additionally, active metabolites of morphine (morphine-6-glucuronide) and meperidine may accumulate, causing prolonged activity. Fentanyl and hydromorphone may be better alternatives. • Muscle relaxants. Succinylcholine should be avoided in patients with hyperkalemia or unknown potassium levels. Cisatracurium and atracurium have organ-independent clearance and should be considered. Additionally, hyperkalemia may increase the effects of depolarizing muscular blockers and opposes the action of nondepolarizing muscular blockers. • Antibiotics. Adjust according to the estimated GFR. • Labs. Frequent electrolytes and ABGs should be considered. • Avoid potassium containing solutions such as lactated Ringer’s. Packed red blood cells contain ∼4 mEq/unit and can increase with storage time (caution with multiple or older

units). • Postoperative mechanical ventilation and ICU admission may be required.

INTUBATION/EXTUBATION CRITERIA Chitra Ramasubbu, MD

BASICS DESCRIPTION

• In the US, 1–3 million patients annually require intubation and mechanical ventilation outside of the OR. This decision typically stems from the need to maintain airway patency, protection against aspiration, or provide oxygenation and ventilation for pathologic pulmonary processes. – In the OR, intubation is typically dependent on the surgical procedure and patient comorbidities; apnea or respiratory depression is drug-induced. • The decision to extubate is of considerable consequence, as delayed extubation is associated with increased duration of mechanical ventilation and increased mortality. Criteria include subjective, as well as objective parameters. – However, because intubation is typically performed to facilitate the surgical procedure, extubation criteria centers around adequate reversal of neuromuscular blocking drugs and the return of airway reflexes from perioperative medications. PHYSIOLOGY PRINCIPLES

• Normal breathing is described as negative pressure ventilation. The diaphragm and chest wall generate negative intrapleural pressures by moving caudally and with chest wall expansion, respectively. Air movement, with resultant lung expansion, results from the creation of a pressure gradient from the oropharynx to the alveoli. • Mechanical ventilation, on the other hand, is described as positive pressure ventilation (PPV), and has effects on the pulmonary and cardiovascular system. • Pulmonary effects of mechanical ventilation may include – Improvement in oxygenation, lung compliance, and V/Q matching – Increased functional residual capacity (FRC) with resultant decreases in shunt and improved oxygenation. – Decreased work of breathing (WOB) – Improved respiratory acidosis • Cardiovascular effects of mechanical ventilation may include – Improve cardiac function in patients with cardiac dysfunction by improving arterial content of oxygen to the coronaries. – Decreased ventricular afterload from increased intrathoracic pressures ANATOMY

• The larynx is a cartilaginous skeleton with ligaments and muscle. There are nine cartilages including the thyroid, cricoid, epiglottis, arytenoids (paired), corniculate (paired), and cuneiform (paired). • Sensory innervation

– Nose mucous membrane: Ophthalmic branch (V1) and the maxillary branch (V2) of the trigeminal nerve – Hard and soft palate: Palatine nerves from the trigeminal nerve – Anterior 2/3rd of tongue: Lingual nerve; a branch of the mandibular branch (V3) of the trigeminal – Posterior 1/3rd of tongue: Glossopharyngeal nerve (CN IX) – Sensation of taste: Anterior 2/3rd by the facial nerve (CN VII), posterior 1/3rd by the glossopharyngeal nerve – Below the epiglottis to above the vocal cords: Internal branch of the superior laryngeal nerve (SLN), a branch of the vagus (CN X) – Below the vocal cords: Recurrent laryngeal nerve (RLN), a branch of the vagus nerve • Motor innervation – Cricothyroid muscle (vocal cord adductors): External branch of the SLN. – All other muscles of the larynx: RLN (posterior cricoarytenoid muscle is an abductor, the remaining muscles are all vocal cord adductors). • Blood supply is via branches of the thyroid arteries. The external carotid artery gives rise to the superior thyroid artery that branches to the cricothyroid artery. During cricothyrotomy, it is best to stay midline to avoid these vessels.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Intubation complications include airway trauma, physiologic responses like hypertension, tachycardia, increased ocular pressures, arrhythmias, aspiration, and tube malposition. • Mechanical ventilation (PPV) complications include – Decreased cardiac output (CO) from diminished venous return; increased intrathoracic pressure decreases end-diastolic volume and stroke volume of both ventricles. – Increased pulmonary vascular resistance (PVR) resulting in increased right ventricular load; this may limit left ventricular distensibility and CO. • Extubation complications include hypertension, tachycardia, arrhythmias, coughing, breath holding, laryngospasm, airway obstruction, aspiration, increased ocular pressure, sore throat tracheomalacia, and laryngotracheal stenosis. • Vocal cord dysfunction may require intubation to maintain a patent airway – Bilateral paralysis of the SLN: Hoarseness and easy tiring of voice. No airway compromise. – Bilateral partial transection: The abductor portion is more prone to injury and results in unopposed adduction. The vocal cords meet in the midline and cause complete airway obstruction. – Bilateral paralysis of the vagus nerve: Affects both SLN and RLN with resultant flaccid, midpositioned vocal cords. Airway control is not a problem, but phonation is affected significantly (neuromuscular blocking drugs).

PERIOPERATIVE RELEVANCE

• General intubation criteria (any 1 of the following): – Cardiac or respiratory arrest – Loss of consciousness – Hemodynamic instability <70 mm Hg

– PaO2 <45 mg despite supplemental oxygen

• Objective intubation indications (≥2 of the following, in the context of respiratory distress): – Respiratory rate (RR) >35/min or <6/min – Oxygen desaturation <90% despite adequate supplemental oxygen – Tidal volume (VT) <5 mL/kg – Vital capacity <15 mL/kg – SBP <90 mm Hg – pH <7.20 and decreased from onset – PaCO2 >50 mm Hg

– Alveolar-arterial gradient (A-a gradient) >350 mm Hg on 100% O2

• Intubation indications in the intensive care unit (ICU) – Airway patency – Aspiration protection – Tracheobronchial toilet – Route for airway pressure therapy – Neurological: central loss of ventilatory drive, spinal cord injury, brain injury, Guillain– Barré syndrome (GBS), phrenic nerve injury – Chest wall: flail chest, rib fractures • Intubation indications in the OR settings – Airway control – Unobstructed leak-free airway for prolonged ventilation – Thoracoabdominal surgery – Head and neck surgery – Risk of aspiration – Positioning (prone, lateral decubitus) – Resuscitation of the moribund patient – Preemptive utility if feared that ventilation/intubation may later become impossible. • Weaning from extubation should be considered as early as possible in both the ICU and the OR. In the ICU, the majority are successfully weaned on first attempt (physicians frequently underestimate the ability of patients to be successfully weaned). In the ICU, the initial weaning is a two-step process and begins with assessment of readiness to wean, followed by suitability to extubate. • Readiness to wean – Clinical assessment for an intact cough reflex, absence of excessive tracheobronchial secretions, and resolution of acute phase of disease causing the intubation – Objective assessment with a rapid shallow breathing index (RSBI). It is calculated as RR/VT. A value of <100–105 breaths/min/L predicts successful spontaneous breathing test (SBT) with a sensitivity of 0.97 and specificity of 0.65. • Suitability to extubate can be assessed objectively with the SBT. The initial SBT should last for 30 minutes and consists of T-tube breathing or low levels of PS (5–8 cm H2O) with or without 5 cm H2O PEEP while making assessments of – Adequate mentation

– Stable cardiovascular status (heart rate (HR) ≤140 bpm, SBP 90–160 mm Hg, minimal or no vasopressors) – Stable metabolic status – Adequate oxygenation SaO2 >90% on fraction of inspired oxygen (FiO2) ≤40% or PaO2/FiO2 ≥150 mm, PEEP ≤8 cm H20

– Adequate ventilation RR ≤35 breath/min Mean inspiratory pressure (MIP) ≤20–25 cm H2O VT >5 mL/kg

Vital capacity >10 mL/kg • Failed SBT criteria include – RR >35 breaths/minute for >5 minutes – SaO2 <90% for >30 seconds or PaO2 ≤50–60 mm Hg on FiO2 ≥50% – PaCO2 >50 mm Hg

– HR >140 bpm – SBP >180 or <90 mm Hg – pH <7.32 – Increased WOB, cyanosis – Agitation, anxiety – Depressed mental status – Cardiac arrhythmias • Causes of failed SBTs include – Psychological dysfunction (anxiety, agitation, delirium) – Infections – Electrolyte abnormalities – Respiratory load (COPD, asthma, pulmonary edema, infiltrates, secretions, edema) – Cardiac load (ischemia, increased metabolic demand, CHF, anemia) – Nutrition (deconditioning, malnutrition, obesity) – Neuromuscular disease (depressed central drive, GBS, myasthenia gravis) – Endocrine (hypothyroidism, hyper/hypoglycemia, adrenal insufficiency) • Pressure support ventilation (PSV) as a weaning mode after a failed SBT has strong support in the literature. The literature does not support the use of synchronized intermittent mandatory ventilation (SIMV) alone for weaning. Little data exists for the use of SIMV/PSV combined. • Noninvasive ventilation may shorten the duration of intubation in patients with hypercapnic respiratory failure. However, in hypoxic respiratory failure, it could be used with caution in the event of extubation failure. • Cuff-leak test involves deflating the cuff or occluding the ETT, and observing if the patient can breathe around the tube. – Failed leak test does not mean failed extubation, but that if extubation is performed, they may require close monitoring. – A positive leak test does not guarantee successful extubation.

• Reasons not to extubate, even when the patient meets extubation criteria include unstable Cspine, inability to protect airway, likely to return to the OR, and potentially difficult reintubation. • Tracheostomy may be required in patients who fail extubation, as prolonged intubation may cause airway edema and injury. – Advantages include decreased WOB, comfort, patient communication, and pulmonary hygiene. – Disadvantages include risk of tracheal stenosis, infection, and procedure related complications. • Extubation criteria in the OR has unique challenges of its own – Adequate oxygenation – Adequate ventilation – Full reversal of neuromuscular blockage (5 second head lift, train-of-four, sustained tetany) – Hemodynamic stability – Mental status intact – Return of reflexes (cough, gag) – Adequate acid–base status – Normothermia – Adequate pain control – Stable metabolic status – Adequate volume status – Electrolytes • Potential difficult extubations postoperatively include – History of a difficult intubation – Sleep apnea – Airway edema – Postsurgical complications from thyroid surgery (RLN injury risk), diagnostic laryngoscopy, uvulopalatoplasty, carotid endarterectomy (hematoma, nerve palsies), cervical spine procedures, and maxillofacial surgery.

EQUATIONS

RSBI = RR/tidal volume (VT)

REFERENCES

1. oles JM, Bion J, Connors A, et al. Weaning from mechanical ventilation. Eur Respir J. 2007;29(5):1033–1056. 2. acIntyre NR, Cook DJ, Ely EW Jr, et al. Evidence-based guidelines for weaning and discontinuing ventilatory support: A collective task force facilitated by the American College of Chest Physicians; the American Association for Respiratory Care; and the American College of Critical Care Medicine. Chest. 2001;120(6 Suppl):375S–395S. 3. ongnecker DE, Brown DL, Newman MF, et al. Anesthesiology, 1st edn. New York: McGraw Hill, 2008, Chapter 83.

ADDITIONAL READING

• Miller RD, Fleisher LA, et al. Miller’s Anesthesia, 6th edn. Philadelphia: Elsevier Churchill Livingstone, 2005, Chapter 75.

See Also (Topic, Algorithm, Electronic Media Element) • Difficult airway • Acute respiratory distress syndrome • Tracheostomy

CLINICAL PEARLS

• The incidence of unplanned extubation ranges from 0.3% to 16%, 83% of which are initiated by the patient. Almost half of patients who self-extubate do not require reintubation. • SBTs do not guarantee that the patient will remain extubated, especially if the airway is unstable or the patient is unable to clear secretions. • If intubation was difficult, airway edema should be suspected.

JET VENTILATION Huafeng Wei, MD, PhD

BASICS DESCRIPTION

• Method of ventilation that is characterized as an open system, with high frequency, and low tidal volumes. • Inspiration is characterized as positive pressure, jet pulsed breaths delivered via a jet nozzle. Exhalation occurs passively and around the jet nozzle; there is no dedicated expiratory limb. • Jet ventilation may be performed supraglottically, infraglottically, or transtracheally. Furthermore, it can be delivered manually or by automatic devices. • Anesthesia providers utilize jet ventilation when the operative field needs to be shared or still; or in the formidable “cannot ventilate, cannot intubate” difficult airway. PHYSIOLOGY PRINCIPLES

• Distinguishing and desirable features of jet ventilation include an open system, high frequency, and low tidal volumes. – Open system for inspiration and exhalation. The internal diameter (ID) of the jet nozzle is small and does not “seal” the airway (unlike the endotracheal tube (ETT) cuff). Furthermore, there is no dedicated expiratory limb (unlike controlled mechanical ventilation (CMV)); instead air egresses out and around the nozzle. Additionally, the jet pulsed inspiratory breaths entrain air via the Venturi effect (high speed pulses generate negative pressures on the gas flow edge that drags air or oxygen from the opening environment into the airway). – High frequency (>60 breaths/minute). Results in “auto-PEEP” (positive end-expiratory pressure) from air trapping and subsequent alveolar opening; without this effect, the low tidal volumes generated would not be able to insufflate alveoli and optimize V/Q matching. Thus, this is a desired effect that increases airway pressures (Paw) and PaO2, but

at the risk of hypercapnia and barotrauma. – Low tidal volumes. Correspond to low peak airway pressures (PIP) and intrathoracic pressures, with resultant increases in venous return. • Components of jet ventilation include a gas source, jet valve, and jet nozzle. – Gas source: Oxygen or oxygen mixed with air from either a wall source or cylinder. – Jet valve: Electronically or manually controlled valve to generate jet pulses when it opens and closes. Gas passes intermittently through the valve to produce jet pulses at different frequency. – Jet nozzle: Any tubing with an ID around 2 mm to deliver jet pulses from the jet valve. These are usually disposable compliant tubes at various lengths (e.g., 14G or 16G angiocatheter, transtracheal jet catheter, Cook tube exchanger, and soft suction catheter). • Working parameters and settings include respiratory frequency, driving pressure, inspiration time, FiO2, and humidification.

– Respiratory frequency: 15–150 breaths/minute. As frequency is increased, exhalation time is reduced and can result in physiologically beneficial auto-PEEPing. Air build-up, due to insufficient time for exhalation, results in alveolar opening with consequent improvements in V/Q matching and oxygenation. High frequencies result in reduced chest wall excursions, thereby providing a more “still” surgical field. However, the shorter exhalation times combined with the smaller tidal volumes compared to CMV results in less CO2

elimination (hypercarbia) and greater dead space ventilation (inefficient ventilation). – Driving pressure refers to the pressure applied to the jet valve. In adults, settings usually start at ~20–25 Psi, with a maximum of 50 Psi. Driving pressure is a major determinant of tidal volume; increases result in higher tidal volumes and minute ventilation. – Inspiration time is typically set at 30–40%. It dictates the time spent in insufflation versus exhalation. By increasing this value, tidal volumes and oxygenation (due to reduced exhalation time and auto-PEEPing) are increased – FiO2: Is set at 100% and is the oxygen concentration at the jet nozzle. The actual FiO2 is significantly less in the alveoli due to Venturi effects and the open system (Figure 1)

FIGURE 1. Venturi effect entrains room air at the level of the jet nozzle.

– Humidification: For prolonged use of jet ventilation, gas from jet pulses should be humidified to avoid airway mucus membrane damage or formation of airway mucus clot and airway obstruction. • Monitoring during jet ventilation is limited because it is an open system. The following cannot be accurately monitored or measured. – FiO2. Decreases along the axis of the airway towards alveoli due to air entrance from Venturi effects. The entrained air from the surrounding opening system mixes with and dilutes the injected oxygen from the jet valve. This decreases the actual oxygen at the alveolar gas exchange site. – Partial pressure of end-tidal of carbon dioxide (PetCO2). Varies along the axis of the

airway due to the opening system. – Airway pressure. Increases along the axis of the airway due to air trapping, especially at high frequency. – Tidal volume. Primarily depends on the driving pressure.

ANATOMY

Approaches of jet ventilation include supraglottic, infraglottic, and transtracheal. • Supraglottic jet ventilation (SJV). Jet nozzle is positioned above the vocal cords with the air aimed toward the glottic opening. Non-invasive and may have less incidence of barotrauma compared to other approaches; additionally, faster to set up. Can be utilized in “cannot intubate, cannot ventilate” and difficult airway scenarios as well as in upper GI endoscopy cases. Also applicable to when the jet ventilator is attached to an LMA adaptor. • Infraglottic jet ventilation. Jet nozzle is positioned below the vocal cords. Has less ambient air entrainment (from Venturi effect) and possibly sore throat than supraglottic access. Utilized when sharing the airway; additionally, also applicable to when the jet ventilator is attached to an ETT adaptor • Transtracheal jet ventilation (TTJV). Jet nozzle is attached to cricothyroidotomy access. Invasive and higher risk of barotrauma (up to 10% in emergent airway access). Utilized in “cannot ventilate, cannot intubate” scenarios; however, must be avoided in complete upper airway obstruction to prevent barotrauma. PHYSIOLOGY/PATHOPHYSIOLOGY

• Barotrauma occurs when pressure builds up in a closed tissue pocket, similar to when a balloon is constantly blown up until it eventually ruptures. The high-pressure system can result in injuries including pneumothorax, pneumomediastinum, and subcutaneous emphysema. Avoid jet ventilation in known barotrauma or where there is upper airway obstruction that would preclude gas egress/exhalation. Additionally, some suggested preventative measures include – Begin to learn and use jet ventilation in elective cases rather than during emergent TTJV – Keep the airway system open and avoid pressure building up in a closed tissue pocket – Consider using noninvasive jet ventilation (supraglottic) – Implement low driving pressures (<25 Psi), low frequency (<120 breaths/minute) • Hypercapnia. Worsened with high-frequency jet ventilation, particularly in obese patients, reduced chest wall compliance, or COPD with increased baseline CO2 levels. Consider switching to CMV periodically to check PetCO2 to avoid hypercapnia or hypocapnia. Can

check ABG if arterial line is available. May be treated by increasing tidal volumes (increase driving pressure or inspiratory time, or decrease respiratory rate). • Insufficient oxygenation can result from insufficient alveolar expansion (insufficient ventilation). Seen more commonly in patients with baseline pulmonary disease. May be prevented by increased FiO2, driving pressure, or inspiratory time. Adding ambient oxygen can increase the delivered FiO2.

• Inadequate humidification may result in necrotizing tracheobronchitis and mucus clotmediated airway obstruction. Use humidification methods if available especially for

prolonged use of jet ventilation. (Current clinical studies do not identify an agreed upon time point).

PERIOPERATIVE RELEVANCE

• With its three features of open system, high frequency, and small tidal volumes, jet ventilation is often utilized to support respiration and perform mechanical ventilation in certain clinical scenarios. • Open systems – “Cannot ventilate, cannot intubate” emergent airway. Included in the ASA difficult airway algorithm. TTJV is comparatively faster, easier to perform, and more often used than emergent tracheostomy. A cricothyroidotomy is performed with either a commercially available cricothyroidotomy needle or a 14G or 16G angio catheter. – GI endoscopy; SJV via a nasal airway allows oxygenation and ventilation without intubating or other airway devices that are invasive or preclude endoscopy. – Difficult airway management. Allows oxygenation while a definitive airway is attained, as during the process of tracheal intubation under direct laryngoscopy or a fiberoptic bronchoscopy. – ENT cases with an open airway such as rigid bronchoscopy, vocal cord, or other upper airway surgeries. During surgical procedures of the upper respiratory tract, surgeons and anesthesia providers must share the airway, and the use of an ETT may obscure access to the surgical site; conversely, surgical instruments can preclude tight sealing of the airway. High-frequency jet ventilation (HFJV) is used to continuously or intermittently provide oxygenation and ventilation. – Thoracic or pulmonary cases such as one lung ventilation, bronchofiberoptic examination or resection of airway tumors, tracheal resection, bronchopleural fistulas • High frequency to provide oxygenation with minimal diaphragm movement – Electrophysiology procedures such as atrial fibrillation or atrial flutter ablations. Less movement allows for more precise mapping and ablation. May reduce the operating time relatively. – Shock wave lithotripsy. CMV or SV via an LMA can result in significant respiratory movement and is akin to hitting a “moving target.” Jet ventilation may be implemented at high frequency and therefore minimize the diaphragm movement and provide optimistic environment for lithotripsy. • Low tidal volume and low intrathoracic pressure. Serves to minimize interference with venous return and may improve hemodynamic in patients with hypovolemia or shock. HFJV (RR at 100/min) seems to be better than CMV to maintain BP and cardiac output during hypovolemia in animal studies. Synchronization of the heart rate with breathing using the R wave of the EKG to trigger jet ventilation has been shown to improve cardiac function in animal studies. • Total IV anesthetic technique is utilized to maintain general anesthesia when utilized in this capacity. A balanced technique utilizing sedatives, opioids, or muscle relaxants may be utilized depending on the case specifics and the needs.

REFERENCES

1. ourgain JL, Desruennes E, Fischler M, et al. Transtracheal high frequency jet ventilation for endoscopic airway surgery: A multicenter study. Br J Anaesth. 2001;87(6):870–875. 2. hra G, Gockner G, Kashanipour A, et al. High-frequency jet ventilation in European and North American institutions: Developments and clinical practice. Eur J Anaesthesiol. 2000;17(7):418–430. 3. Wei HF. A new tracheal tube and methods to facilitate and placement in emergency airway management. Resuscitation. 2006;70:438–444. 4. ezaie-Majd A, Bigenzahn W, Denk D, et al. Superimposed high-frequency jet ventilation (SHFJV) for endoscopic laryngotracheal surgery in more than 1500 patients. Br J Anaesth. 2006; 96:650–659.

5. Peng J, Ye J, Zhao Y, Liang J, Huang H, Wei H, Peng S. Supraglottic jet ventilation in difficult airway management. J Emerg Med. In Press, 2012.

6. Dziewit JA, Wei H. Supraglottic Jet Ventilation Assists Intubation in a Marfan’s Syndrome Patient with a Difficult Airway. J Clin Anesth. 2011;23:407–409. 7. Dziewit JA, Wei H. Supraglottic Jet Ventilation Assists Intubation in a Patient with Difficult Airway Due to Unrecognizable Supraglottic Structures. J Anesth Clin Res. 2011;2:141. doi: 10.4172/2155-6148.1000141.

ADDITIONAL READING

• Boyce JR, Peters GE, Carroll WR, et al. Preemptive vessel dilator cricothyrotomy aids in the management of upper airway obstruction. Can J Anesth. 2005;52:765–769. • Caplan RA, Benumof JL, Berry FA, et al. Practice guidelines for management of the difficult airway. An updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology. 2003;98:1269–1277. See Also (Topic, Algorithm, Electronic Media Element)

• Pneumothorax • Difficult airway • Cricothyroidotomy • Bronchoscopy

CLINICAL PEARLS

• Jet ventilation has unique features that differentiate it from CMV. It provides an open airway system, has respiratory rates between 12 and 1,000 breaths/minute and greater dead space ventilation (Vd in adults is usually 150 mL; however, can still provide efficient oxygenation and ventilation with unclear mechanisms). Additionally, jet ventilation has low PIP, auto-PEEPing is a desired feature (results from high frequencies), inhalational anesthetics cannot be used, and is poorly humidified. • Perioperative utilization includes situations where a “still” surgical field is desired, there is a shared surgical site, and difficult airway management. • Unfortunately, there is a poor ability to monitor FiO2, PetCO2, Paw, and tidal volume.

JUGULAR VENOUS OXYGEN SATURATION (SJO2) Keren Ziv, MD Linzy Fitzsimons, MD

BASICS DESCRIPTION

• Jugular venous oxygen saturation (SjO2) is a measurement used to indirectly assess global

cerebral oxygen extraction by measuring the balance of oxygen consumption and delivery in the brain. It is the most widely used method of continuous cerebral oxygenation monitoring. • It involves percutaneous catheter insertion into the jugular bulb that then measures SjO2 via fiberoptic reflectance oximetry or by manual blood draws analyzed via co-oximetry. • Studies have demonstrated that early SjO2 catheter insertion may improve patient outcome. PHYSIOLOGY PRINCIPLES

• The brain is an exceedingly, metabolically active organ and accounts for ∼20% of the resting total body O2 consumption. Most of the oxygen consumption is used for excitation and conduction of the neuronal signals in the brain, and a smaller amount is used for synthesis and metabolism of neurotransmitters as well as cellular homeostasis. • Cerebral metabolic oxygen consumption (CMRO2) is normally 3–3.5 mL of O2 per 100 g of

brain tissue per minute (3.5 mL/100 g/min). • SjO2 provides an assessment of the balance between oxygen delivery and consumption in the brain, to allow an estimate of the CMRO2.

– Normal values range from 50% to 75% (equating to an approximate 25–50% oxygen extraction). – Saturation of jugular venous blood is dependent on the cerebral blood flow (CBF), arterial saturation, and CMRO2.

• The calculation of SjO2 utilizes the Fick equation: CMRO2 = CBF × (CaO2–CjO2), where

CaO2 is arterial oxygen content and CjO2 is jugular (venous) oxygen content; it represents

the arteriovenous oxygen difference. – CMRO2 ∼ [CBF × 1.34 × Hb(SaO2–SjO2)]. Oxygen has a blood solubility of 0.003; the

dissolved contribution is negligible and hence deleted from the equation. – Assuming that Hb and SaO2 are constant, SjO2 ∼ CBF/CMRO2. Thus, SjO2 is predominantly dependent on the SaO2, CMRO2, and CBF.

• During SjO2 monitoring, a spectrophotometric catheter using three light wavelengths is used to measure both the hemoglobin value and oxygen saturation.

ANATOMY

• The majority of the blood from the brain drains into the internal jugular (IJ) veins therefore making it a practical site to assess for cerebral venous oxygen saturation. – The left IJ predominately drains subcortical areas while the right IJ predominately drains the cortical areas. Studies have suggested that: – Oxygen saturations are similar in both IJ veins, particularly with diffuse cerebral injury. – Focal disease may produce a larger saturation difference between the sides. – Catheter placement is typically on the side of greatest flow; some advise placement on the side of the injury (controversial). • The catheter can be inserted into the IJ vein between the two heads of the sternocleidomastoid muscle (distally) or at the level of the cricoid ring (proximally) and is directed cephaladly toward the jugular bulb. On radiography, the tip should be at about the C1–C2 vertebrae and as close to the skull base as possible, to minimize facial vein contamination.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Decreased SjO2 suggests ischemia and can result from increased oxygen extraction (demand)

or decreased CBF (supply). – Increased demand Intracranial hypertension Seizures Pyrexia – Decreased supply Systemic hypoxia Hypotension or vasospasm leading to decreased CBF Intracranial hypertension with decreased CPP • Increased SjO2 can result from decreased brain oxygen extraction (demand), increased CBF (supply), or impaired oxygen extraction. – Decreased demand (CMRO2)

Increased cell death suggesting worsening brain damage – Increased supply Hyperemia – Impaired oxygen extraction Shunting (arteriovenous malformations); oxygenated blood does not perfuse ischemic areas (bypasses). Failed oxygen extraction. – Measurement errors: Contamination from extracranial drainage; can range from 0% to 6.6% (mean 2.7%). Sampling a rate >1–2 mL/minute can result in sampling or contamination by the facial vein. • Severe brain injury – CBF and CMRO2 are altered during the first few days and SjO2 provides a measure of objective insight into worsening brain injury. – Following injury, patients are at increased risk of secondary cerebral insults caused by hypoxia and ischemia, leading to further brain damage.

– SjO2 unfortunately provides information on a global scale and may therefore be inaccurate in situations dealing with local ischemia. It may be incorrectly assumed that SjO2 is

normal in a heterogeneous brain because areas of local ischemia may be compensated for by areas of luxury perfusion. • Potential complications of insertion – Carotid artery puncture (1–4%) – Thrombosis – Hematoma – Infection

PERIOPERATIVE RELEVANCE

• Cerebrovenous oxygen saturation, in combination with hemodynamic and intracranial data, can aid in the detection and treatment of cerebral ischemia following stroke, trauma, cardiac arrest, or cardiopulmonary bypass. • Although individual SjO2 values may prove to be less than accurate, using SjO2 trends is a

useful tool in the perioperative period to help guide both the anesthetic and intensive care unit management. • While the normal range of SjO2 is considered to be 50–75%, it is not clear whether this is

true for patients with TBI. Studies, however, have demonstrated that a single episode of SjO2 <50% is associated with a twofold increase in mortality. Therefore, current recommendations dictate maintaining the SjO2 between 55% and 75% in order to extend

the margin of error. • SjO2 may be altered by several coincident factors such as hemoglobin concentration, temperature, oxygenation, and carbon dioxide levels. Other modalities of measuring oxygen utilization such as near-infrared spectroscopy are often monitored in addition to SjO2.

• Choosing side to monitor. One technique is to test intracranial compliance. This may be done by compressing each jugular vein, one at a time, and observing the rise in ICP. The side with the greatest increase in ICP drains more blood and suggests a larger vascular territory of the brain. When there is no difference, the right side is often chosen as it is more commonly the dominant anatomical site. • Cannulation technique. Placement should be performed in the horizontal or Trendelenburg position, while avoiding ICP >20 mm Hg.

EQUATIONS

• CMRO2 = CBF × (CaO2–CjO2); where CMRO2 is the cerebral metabolic oxygen

consumption, CBF is cerebral blood flow, CaO2 is the arterial oxygen content, CjO2 is the

jugular venous oxygen content. • SjO2 = SaO2 – (CMRO2/[CO × Hb × 1.39]); where SaO2 is arterial blood oxygen saturation, CMRO2 is the cerebral metabolic oxygen consumption, CO is cardiac output, Hb is hemoglobin, and 1.39 represents the amount of oxygen that one gram of hemoglobin can carry.

REFERENCES

1. hite H, Baker A. Continuous jugular venous oximetry in the neurointensive care unit – A brief review. Can J Anesth. 2002;49(6):623–629. 2. ohlwink UK, Figaji AA. Methods of monitoring brain oxygenation. Childs Nerv Syst. 2010;26:453–464.

3. Gopinath SP, Valdaka AB, Uzura M, et al. Comparison of jugular venous oxygen saturation and brain tissue PO2 as monitors of cerebral ischemia after head injury. Crit Care Med. 1999;27(11):2337–2345.

4. Macmillan CSA, Andrews PJD. Cerebrovenous oxygen saturation monitoring: Practical considerations and clinical relevance. Intensive Care Med. 2000;26:1028–1036.

ADDITIONAL READING

• Steiner IA, Andrews PJD. Monitoring the injured brain: ICP and CBF. Br J Anaesth. 2006;97:26–38.

See Also (Topic, Algorithm, Electronic Media Element) • Mixed venous oxygen saturation • Pulse oximetry • Cerebral metabolic oxygen consumption (CMRO2) • Intracranial hypertension

CLINICAL PEARLS

• SjO2 monitoring indirectly assesses the brain’s ability to extract and metabolize oxygen; it

relies on the Fick principle of oxygen consumption (supply versus demand). At this time, there are no direct methods to measure the adequacy of the oxygen supply at the cellular level. • May be inaccurate in measuring focal ischemia. • Assumptions are dependent on the CMRO2 and CBF being coupled. • Research regarding use in children with TBI is limited.

JUNCTIONAL RHYTHM Piotr K. Janicki, MD, PhD Marek Postula, MD, PhD

BASICS DESCRIPTION

• Junctional heart rhythms and premature junctional (escape) beats originate from the area around the atrioventricular (AV) node. They occur when the AV node takes over as the primary pacemaker site in the heart because either the – Sinoatrial (SA) node has failed, or the – AV node is firing faster and overtakes the SA node • Junctional rhythms classification – Junctional rhythm: Rate is 40–60 beats per minute (bpm). – Junctional accelerated rhythm: Rate is 60–100 bpm. – Junctional tachycardia: Rate is >100 bpm. • Junctional rhythms are an example of a supraventricular rhythm in which the QRS complex morphology is usually narrow (<0.12 seconds) and regular. There are no P waves seen before the QRS complexes; instead, they occur either simultaneously with the QRS complexes or are retrograde. EPIDEMIOLOGY Prevalence

Common in patients with sick sinus syndrome or in patients who have significant bradycardia that allows the AV nodal region to determine the heart rate Prevalence

• Episodes of AV nodal reentrant tachycardia may occur at any age. However, commonly presents for the first time in childhood or adolescence. • Common during sleep in children and in athletic adults.

Morbidity

• Junctional ectopic tachycardia (JET) often presents in the first 24–48 hours after surgery for congenital heart defects (1). • A congenital form exists with normal cardiac anatomy, and a positive family history is present in up to 50% patients with congenital form of junctional tachycardia. Mortality

• No evidence exists to suggest an increased mortality for incidental junctional rhythm. • The permanent form of JET is rare and constitutes <1% of pediatric arrhythmias. It commonly leads to cardiomegaly and congestive heart failure in up to 60% of patients, with an associated mortality rate of 35%.

ETIOLOGY/RISK FACTORS

• Demographics – Younger population and/or athletic individuals during periods of increased vagal tone on the SA node. • Coexisting disease – Ischemia of the AV node, especially with acute inferior infarction involving the posterior descen-ding artery, the origin of the AV nodal artery branch – Sick sinus syndrome (including drug-induced) – Chronic obstructive pulmonary disease (COPD) – Less common: Congenital form, systemic amyloido-sis, diphtheria, acute rheumatic fever, Lyme disease • Surgery or procedure – Valve surgery – Direct current cardioversion – Cardiac catheterization – Maneuvers that enhance vagal tone: Laparoscopy, peritoneal retraction, eye surgery, etc. • Medications – Inhaled anesthetics; most commonly with enflurane – Drugs that induce sinus bradycardia: Beta-blockers, calcium channel blocker, and most antiarrhythmics – Digoxin toxicity – Isoproterenol infusion • Metabolic – Hyperkalemia • Increased adrenergic tone

PHYSIOLOGY/PATHOPHYSIOLOGY

• Junctional rhythms (and escape beats) are the result of – SA node that has failed due to ischemia, intrinsic disease, vagal tone, changes in autonomic tone, or medications that suppress the SA node. – AV nodal firing at a faster rate than the SA node; subverts hierarchy and overtakes a “normal” sinus node. Less commonly, it is observed in digitalis toxicity, following cardiac surgery (particularly valve replacement), during acute myocardial infarction, or during isoproterenol infusion (2). • Junctional rhythms can result in a decreased or absent atrial contribution or “kick” during ventricular diastole. This can result in decreased preload and hence, stroke volume (Frank– Starling curve); ultimately leads to a decrease in cardiac output (stroke volume times heart rate). This discor-dant contraction can also result in atrial contraction against a closed tricuspid valve, resulting in increased right atrial and central venous pressures.

PREVENTATIVE MEASURES

• Congenital form. There are no preventative measu-res or perioperative factors that have been identified to target prevention at the time of surgical repair. • Symptomatic cases may benefit from a consultation with a cardiologist to better define the

etiology and approach to prevention.

PREOPERATIVE ASSESSMENT Intraoperatively

• EKG findings – Rate: Typically 40–60 bpm; accelerated rhythms reach 60–100 bpm, while junctional tachycardia can be as high as 100 bpm. – P wave (atrial depolarization). Is either missing or inverted. When present, it can be seen before, during (hidden), or after the QRS complex and is most noticeable in leads I and II, and aVL. – P–R interval. When the P wave occurs before the QRS complex, the interval will be <0.12 seconds. – QRS wave. Typically a normal waveform is seen; may appear abnormal when the P wave falls within the QRS complex. – Escape beats. Premature beat, with above-described P and QRS waveforms. No pause is seen prior to the next beat. • Physical exam – Regular pulse – Prominent jugular venous pulsations – Cannon “a” waves may be seen on central venous pressure waveforms due to the right atrium contracting against a closed tricuspid valve. • Labs – Electrolytes – Digoxin level (if appropriate) Awake or Outpatient Setting • Symptoms are typically nonspecific and include palpitations, fatigue, poor exercise tolerance, dyspnea, and presyncope. • A two-dimensional echocardiograph in patients with suspected structural heart disease • A stress echocardiograph or nuclear imaging test in patients with symptoms consistent with coronary ischemia • An implantable loop recorder may help diagnose junctional rhythm in patients with very infrequent symptoms. • In specific cases an electrophysiologic study (EPS) or invasive electrophysiologic evaluation. DIFFERENTIAL DIAGNOSIS

• AV block • AV dissociation • Atrioventricular nodal reentry tachycardia (AVNRT) • Digitalis toxicity • Sinus node dysfunction • Low atrial ectopic foci can cause inverted P waves.

TREATMENT • Intraoperative treatment is dependent on the underlying cause and if the rhythm is causing hemodynamic instability (3). The junctional rhythm serves as an escape mechanism to maintain the heart rate during periods of bradycardia or asystole and should not be suppressed. – Underlying cause. Ischemia and metabolic derangements should be identified and treated accordingly. Treatment of digitalis intoxication may include correcting potassium levels and/or administering atropine, digoxin immune Fab (Digibind).

– Stable patients. Pharmacologic therapy is not typically needed when junctional rhythms result from increased vagal tone. – Unstable patients. Decrease the dose of inhalational anesthetics. Administer anticholinergic drugs such as glycopyrrolate or atropine to speed up the SA node and re-establish hierarchy. Vasopressor support as needed JET is generally treated medically; amiodarone may be the best antiarrhythmic medication. • Postoperative JET – Initial approach: Discontinue vagolytic agents and reduce the doses of inotropic agents. – Serum calcium and potassium should be normalized. – IV amiodarone is the first-line agent in patients with JET from all causes. Beta-blockers, with or without procainamide may be also considered; however beta-blockers may depress myocardial contractility, and procainamide may accelerate JET – When JET is not eliminated – In rare, resistant, life-threatening cases, transcatheter radiofrequency ablation or modification of the His bundle may be necessary. – Postoperative JET is limited – Core temperature cooling has value in the infant and small child; cooling blankets can be utilized to obtain a temperature of ~34–35°C. • Congenital and adult JET warrant aggressive management, especially in the young, with amiodarone or sotalol.

FOLLOW-UP • Symptomatic cases may benefit from a consultation with a cardiologist and/or an electrophysiologist to better define the etiology and approach to prevention. • Sick sinus rhythm, high-grade, or complete AV block. Patients may be considered for a permanent pacemaker implantation. • Radiofrequency catheter ablation also can be used to treat JET if there is no response to pharmacological therapy. • A treatment option for JET is an AV junction ablation with permanent pacemaker implantation.

REFERENCES

1. Haas NA, Plumpton K, Justo R, et al. Postoperative junctional ectopic tachycardia (JET). Z Kardiol 2004;93(5):371–380. 2. Ufberg JW, Clark JS. Bradydysrhythmias and atrioventricular conduction blocks. Emerg Med Clin North Am. 2006;24(1):1–9.

3. Blomström-Lundqvist C, Scheinman MM, Aliot EM, et al. European Society of Cardiology Committee, NASPE-Heart Rhythm Society. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias–executive summary: A report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society. J Am Coll Cardiol. 2003;42(8):1493–1531.

ADDITIONAL READING

• Libby P, Bonow RO, Mann DL, et al. Specific arrhythmias: Diagnosis and treatment. In: Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine. 8th edition. Philadelphia, PA: WB Saunders, 2007:640–645. • Josephson ME. Clinical Cardiac Electrophysiology. 4th edition. Baltimore, MD: Williams & Wilkins, 2008.

See Also (Topic, Algorithm, Electronic Media Element) • Intraoperative myocardial ischemia • Phosphate

CODES ICD9 • 427.0 Paroxysmal supraventricular tachycardia • 427.89 ICD10 • I47.1 Supraventricular tachycardia • I49.8 Other specified cardiac arrhythmias

CLINICAL PEARLS

• No pharmacologic therapy is needed for asymptomatic, otherwise healthy individuals with junctional rhythms that result from increased vagal tone. • Emergency care includes evaluation of the 12-lead EKG findings, airway protection and oxygenation, and BP support, depending on the cause of the rhythm. • In patients with complete AV block, high-grade AV block, or symptomatic sick sinus syndrome (i.e., sinus node dysfunction), a permanent pacemaker may be needed. The

junctional rhythm serves as an escape mechanism to maintain the heart rate during periods of bradycardia or asystole and should not be suppressed.

FIGURE 1. Junctional rhythm. Rate of 40–60 bpm

FIGURE 2. Accelerated junctional rhythm. Rate of 60–100 bpm

FIGURE 3. Junctional tachycardia. Rate >100 bpm

KASAI PROCEDURE (HEPATOPORTOENTEROSTOMY) Alison R. Perate, MD

BASICS DESCRIPTION General

• The Kasai procedure is a therapeutic/palliative procedure for biliary atresia (BA). BA is characterized by extrahepatic biliary duct fibrosis with some extension into the liver. The obliteration of the extrahepatic bile ducts prevents bile from draining, leading to liver cirrhosis and ultimately liver failure. – Fetal form: 10–20% of cases, born jaundiced, ABSENCE of bile ducts – Perinatal form: 80–90% of cases, healthy neonate, develops symptoms • Not a treatment for Alagille syndrome (intrahepatic biliary fibrosis) • Mostly done via an open technique, but some centers are gaining experience with robotic and laparoscopic techniques. • The liver is mobilized, the porta hepatis is exposed, and the fibrous tissue is excised widely. • A roux-en-y is created with the intestine (typically jejunum) and sutured widely to the porta hepatis. Position

• Supine • Prep from the nipples to the pubic bone

Incision

Right subcostal incision Approximate Time 3 hours

EBL Expected

Typically 10–20 mL/kg, primarily during dissection of the porta hepatis Hospital Stay 2–3 weeks

Special Equipment for Surgery

Intraoperative cholangiography may be done to verify occlusion. EPIDEMIOLOGY Prevalence

5–10/100,000 newborns have BA.

Prevalence

BA is increased in: • Non-Caucasian races • Advanced maternal age • Maternal multiparity • Female sex of baby

Morbidity

• >70% will need a liver transplantation following the Kasai. • It is commonly believed that survival of the native liver is related to the age of the patient at the time of the Kasai with most studies showing best results for those infants under 60 days of age (this is controversial, as some studies show no difference).

Mortality

• Varies widely depending on the surgeon and study • 5-year survival after Kasai ranges from 20% to 70%. • Decreased mortality with open procedure versus laparoscopic

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Hemorrhage can occur at any point due to the proximity of portal vessels. Blood products should be readily available. • Intravascular volume is critical. Excess will cause liver edema. • Liver disease may result in anemia, coagulopathy, decreased total body proteins, vitamin deficiencies, and prolonged drug life.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Lack of appetite • Pruritus • Stigmata of liver disease

History

Patients often present with acholic stools, jaundice, and direct bilirubinemia. The diagnosis is usually made in the first 3–4 months of life. Signs/Physical Exam • Jaundice • +/– Hepatomegaly • Poor weight gain • Ascites • Pale stools

MEDICATIONS

• Preoperative vitamin K 1–2 mg/day • Postoperative steroids, antibiotics, and fat-soluble vitamins

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC • Chemistry panels • Coagulation studies (PT, PTT, INR): Elevated PT can be corrected with vitamin K administration. • Liver function tests: Increased conjugated hyperbilirubinemia

CONCOMITANT ORGAN DYSFUNCTION Liver failure

TREATMENT PREOPERATIVE PREPARATION Premedications

Anxiolysis is not necessary in this age group. Special Concerns for Informed Consent

• Consent for blood transfusion • Consent for arterial line and central line, if needed • Consent for epidural (if no coagulopathy)

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with endotracheal tube • Epidural placed for postoperative pain management. In small infants a caudal catheter is utilized and threaded up to T7–T8. Patient should be assessed for coagulopathy.

Monitors

• Standard ASA Monitors • Arterial line for continuous blood pressure monitoring and lab draws • 2 large-bore IVs for rapid resuscitation • Central line may be necessary if unable to obtain adequate peripheral access or at the surgeon’s request.

Induction/Airway Management

• In the absence of increased intra-abdominal pressure (from ascites), an inhalation induction is acceptable. • An IV induction is preferred in cases where an IV has been placed for preoperative hydration or tests.

Maintenance

• Because of the age of the patient, it is easiest to place a caudal epidural in the lateral position once the patient is anesthetized. – The catheter is threaded cephalad to the low thoracic level (typically T8–T9 corresponds with the incision). – Epidural placement can be confirmed with the injection of radio-opaque dye through the catheter under fluoroscopy. – Epidural solution varies by institution. Bupivacaine 0.25% + opioid (fentanyl) is very common. • Maintenance is typically with volatile agents, oxygen, and air. Avoid nitrous oxide as it can cause bowel distention. Muscle relaxation should be appropriately administered to provide optimal surgical exposure. Consider organ-independent NMBD if severe liver disease. • Normothermia should be maintained; the neonate resorts to non-shivering thermogenesis to maintain heat. • Maintain euvolemia. Hypovolemia will cause decreased cerebral flow from hypotension, but increased intravascular volume increases portal pressures and can result in liver swelling. • Blood products should be ready to administer in the event of portal injury (typically 1 unit of packed red blood cells). If the patient is significantly coagulopathic from liver failure, fresh frozen plasma may also be available. • Incision is usually small, and most of the surgical repair is done after the liver has been externalized from the abdomen. This can result in torquing of portal vessels with resultant hypotension. • Since most of the operation is done outside of the abdomen, there is usually minimal impact on ventilation.

Extubation/Emergence

• Extubation should be considered if the patient is awake, strong, able to protect their airway, and hemodynamically stable. • If an epidural is in place, it should be adequately dosed.

FOLLOW-UP BED ACUITY

Neonatal or pediatric ICU ANALGESIA

Pain can be controlled via epidural +/– IV opioid. If IV opioids are used, the epidural solution should be opioid-free. COMPLICATIONS

• Cholangitis • Bile leak (10–15%) • Malabsorption syndrome • Portal hypertension and subsequent esophageal varices

• Liver failure • Bowel obstruction (10%) • Bleeding • Infection/sepsis (5–10%)

REFERENCES

1. u LN, Chen HL, Chang CJ, et al. Prophylactic oral antibiotics in prevention of recurrent cholangitis after the Kasai portoenterostomy. J Pediatr Surg. 2003;38:590–593. 2. Ure BM, Kuebler JF, Schukfeh N, et al. Survival with the native liver after laparoscopic versus conventional Kasai portoenterostomy in infants with biliary atresia: A prospective trial. Ann Surg. 2011;253(4):826–830.

3. Leonhardt J, Kuebler JF, Leute PJ, et al. Biliary atresia: Lessons learned from the voluntary German registry. Eur J Pediatr Surg. 2011;21(2):82–87.

ADDITIONAL READING

• Puri P, Hollwarth M. . New York: Springer, 2009.

See Also (Topic, Algorithm, Electronic Media Element) • End-stage liver disease

CLINICAL PEARLS

• The Kasai procedure is palliative in most cases. >70% of cases will require a liver transplant. • There is a potential for massive blood loss (relative to the neonate’s blood volume). • Maintain euvolemia. • Epidurals work well for pain control postoperatively. • The biggest postoperative concern is to prevent cholangitis with prophylactic postoperative antibiotic treatment. If cholangitis is suspected, steroids are added.

KIDNEY TRANSPLANTATION Kenneth F. Kuchta, MD

BASICS DESCRIPTION General

• Performed in patients with end-stage renal disease (ESRD) to eliminate or preempt dialysis, prolong longevity, and improve the quality of the recipient’s life. • ESRD can be due to a variety of causes, including diabetes, hypertension, glomerulonephritis, polycystic kidney disease, chronic pyelonephritis, and systemic lupus erythematosus. • Procedure: A “3-way” Foley catheter is sterilely inserted with the additional lumen allowing infusion of fluid before the ureteral anastomosis (and for possible continuous bladder irrigation in the event of clot retention). The extraperitoneal space is dissected to expose the iliac vessels and bladder. The external iliac vein is clamped, and the donor renal vein is anastomosed to it (renal vein-to-iliac-vein anastomosis). The external iliac artery is clamped, and the donor renal artery is anastomosed to it (renal artery-to-iliac-artery anastomosis). The vessel clamps are then removed. A ureteroneocystostomy is then performed (the donor ureter is anastomosed to the recipient’s bladder); the bladder is distended with antibiotic irrigation to aid with visualization and the detrusor muscle of the bladder is dissected away from the mucosa. • Advances in immunosuppression and organ preservation techniques, as well as acceptance of brain death, development of an organ donor network, and establishment of reimbursement mechanisms have all led to the development of renal transplantation as a relatively common procedure. • A limited donor pool has been extended with living donation. Living donors may be related, unrelated “Good Samaritans,” paired or even chain donations. Position Supine

Incision

Lower abdominal to transplant the kidney to the iliac fossa Approximate Time

3 hours; if combined with a pancreatic transplant (in diabetics) time may double EBL Expected

Usually <200 mL Hospital Stay

3–7 days

Special Equipment for Surgery

An organized multidisciplinary transplant team that is integrated with the national organ transplant organization EPIDEMIOLOGY Prevalence

• 17,413 transplants performed in the US in 2008 (1) – 11,382 deceased donors (1) – 5,968 living donors (1) Prevalence

• 547,982 ESRD in the US in 2008 (1) – 382,343 managed by dialysis (1) – 165,639 managed by a kidney transplant (1)

Morbidity

• Cardiovascular and infectious morbidity seem to predominate among those with ESRD. Infection is related to both dialysis access and other independent sources. • Problems with vascular access are an additional common reason for hospital admission.

Mortality

88,620 deaths in patients with ESRD in the US during 2008 (1)

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Taking the often “dry” renal failure patient to an adequately volume loaded state is the goal in renal transplantation. Recipients, however, often have cardiovascular conditions that can put them at risk for CHF. • Once adequate volume loading has been assured, adequate perfusion of the new kidney may need to be supplemented by means of an inotrope such as dopamine. • Low bicarbonate, high potassium, and low hematocrit are expected in these patients; excessive deviations might need to be treated with dialysis or transfusion preoperatively.

PREOPERATIVE ASSESSMENT SYMPTOMS

Any recent changes should be elicited especially with regard to chest pain, dyspnea, or exercise tolerance. History

• Typically patients presenting for renal transplantation will come with an extensive preoperative evaluation. For deceased donor transplants, the goal is to have patients in optimal condition for transplant to occur with limited warning. Despite this, the anesthesia preoperative evaluation may serve as the last chance to ensure that important changes in

the patient’s condition have not occurred. Hence, the preoperative visit may concentrate on: – The usual dialysis schedule and the most recent dialysis – History of chest pain, dyspnea, cardiac history and evaluations, exercise tolerance – In the diabetic patient, the duration of treatment and usual glucose levels – Bleeding tendencies

Signs/Physical Exam

A careful cardiovascular exam, especially paying attention to volume status and apparent changes in the exam MEDICATIONS

Typically ESRD patients are on a plethora of drugs: Beta-blockers, calcium channel blockers, diuretics, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, statins, protein pump inhibitors, laxatives, iron/erythropoietin, vitamins/electrolyte supplements, and insulin (in diabetics) DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, especially potassium level and evidence of acidosis • Preoperative glucose • Hemoglobin and hematocrit • Review any preoperative cardiac workup, including stress tests and EKG.

CONCOMITANT ORGAN DYSFUNCTION

• Diabetes • Hypertension • Cardiovascular disease – About 50% of transplanted patients die of cardiovascular disease or stroke. – The usual risk factors for atherosclerotic cardiovascular disease (smoking, hypertension, abnormal cholesterol and lipid levels, diabetes, male gender, advanced age) are often found in renal failure patients as well. – Renal failure can create challenges for the patients with cardiovascular disease; anemia, volume overload, and labile blood pressures add additional risk for these patients. – For patients with prior transplants, immunosuppressants, graft rejection, and dysfunction can further add to the cardiac risk and management challenges (2). • Pulmonary hypertension • A variety of bleeding abnormalities • Hepatitis C • Anemia

TREATMENT PREOPERATIVE PREPARATION Premedications

As determined by the patient’s coexisting disease and general condition Special Concerns for Informed Consent

Consent for planned or possible invasive monitors, a review of the risks in light of comorbidities, and the possibility of postoperative intubation and ICU admission (though perhaps not especially common) might be appropriate. Antibiotics/Common Organisms

Routine antibiotics for urological procedures. Infectious disease precautions are even more crucial in light of perioperative immunosuppression. INTRAOPERATIVE CARE Choice of Anesthesia

• Most under general anesthesia • Can be done under spinal or epidural anesthesia, and some centers have even reported combined general and regional to improve postoperative pain control and improved respiratory function. Concerns about uremic coagulopathy and remaining heparin from dialysis or potential intraoperative administration have dampened enthusiasm for regional.

Monitors

• Central venous monitoring is useful for monitoring volume loading throughout the perioperative period. Difficult IV access, frequent blood draws, and the potential for dopamine administration might also influence the placement of a central line. Planned thymoglobulin administration (with the risk of vessel sclerosis) also encourages the placement of central lines in some centers although others have successfully administered this drug via a high-flow vessel using a dilute solution. • Arterial line placement and other invasive monitoring are dependent upon the medical condition of the patient. Some centers attempt to minimize arterial line use as the radial artery may be used for dialysis access. • A “3-way” urinary catheter is placed not only to monitor urine output following reperfusion, but is also often clamped with irrigation infused into the bladder during attachment of the ureter to facilitate this portion of the procedure. Complete emptying of the irrigant from the foley following ureteral anastomosis allows a more accurate assessment of urine output from the newly transplanted kidney.

Induction/Airway Management

• Succinylcholine will increase potassium levels 0.5–1 mEq/L (to the same extent as those without renal disease). It can be used if the potassium is not already elevated. • Consider a rapid sequence induction based upon NPO status and diabetic gastroparesis. • As the patient is usually postdialysis, and therefore volume depleted, propofol should be used with caution and etomidate might be considered. Propofol, however, is often well tolerated.

Maintenance

• Muscle relaxant: Cisatracurium offers a theoretical advantage of Hoffman elimination (not

dependent on renal metabolism). Rocuronium, vecuronium, and mivacurium may all be prolonged in renal failure. While a longer acting agent is probably not advisable, these moderate duration relaxants have been used with careful monitoring. • Opioids: Meperidine and morphine in high doses pose concerns with accumulation of renally excreted active metabolites. The metabolite of meperidine, normeperidine, can cause seizures. Fentanyl, alfentanil, sufentanil, and remifentanil drug effects are minimally affected by renal failure. • Volatile agent: Some practitioners avoid sevoflurane due to the potential for renal toxicity. Others are not convinced that this is an issue given the paucity of convincing human data, even in patients with renal dysfunction. • Immunosuppression and hemodynamic management vary by institution; it is best to establish preoperative consensus among the teams involved. Immunosuppression may begin with tacrolimus (often given orally in the preoperative period) followed by steroids and either basiliximab or thymoglobulin. Thymoglobulin must be given slowly (typically over 6 hours), with a 0.22 μm filter and into a high-flow vessel (to reduce vessel sclerosis). • Heparin infusion may be needed if there is concern with the anastomosis. • Lasix and mannitol may be used to induce diuresis. • If CVP is used to manage fluid administration, the plan is to reach the “ideal” level by the time of reperfusion. • Dopamine might be added (perhaps at 2–10 mcg/kg/min) to achieve an adequate blood pressure for renal perfusion. • Periodic checks of electrolytes (and in diabetics, glucose) are advisable.

Extubation/Emergence

Most patients are extubated at the end of surgery. Volume overload or other complications may preclude immediate extubation.

FOLLOW-UP BED ACUITY

ICU typically not needed unless underlying disease or intervening complication requires this level of monitoring ANALGESIA

• Mild-to-moderate pain usually managed with parenteral narcotics, often with a PCA or via epidural analgesia. • Ketorolac and other NSAIDs should probably be avoided due to potential nephrotoxic side effects.

COMPLICATIONS

• Cardiovascular complications: CHF, MI, CVA • Delayed graft function, graft failure, rejection, vascular thromboses • Infections

PROGNOSIS

5-year survival after renal transplantation is 70% versus only 30% in a comparable dialysis group. Serious comorbidities may be reduced or resolve completely after transplantation.

REFERENCES

1. S Renal Data System. , National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2010.

2. Kiberd BA. Cardiovascular disease in kidney transplant recipients. Adv Stud Med. 2007;7:169–178.

ADDITIONAL READING

• Jankovic Z, Sri-Chandana C. Anaesthesia for renal transplantation: Recent developments and recommendations. Curr Anaesth Crit Care. 2008;19:247–253. • Lemmens HJM. Kidney transplantation: Recent developments and recommendations for anesthetic management. Anesth Clin N Am. 2004;22:651–662.

See Also (Topic, Algorithm, Electronic Media Element) • End-stage renal disease • Uremia

CODES ICD9 • V42.0 Kidney replaced by transplant • 585.6 End stage renal disease ICD10 • N18.6 End stage renal disease • Z94.0 Kidney transplant status

CLINICAL PEARLS

• The typical concerns with fluid restriction in renal failure are dramatically altered due to the desire to provide an adequate perfusion to the new kidney. Hence volume loading (and if necessary an inotrope, such as dopamine, at relatively low doses and after adequate volume has been assured) has been the typical management of renal transplants. This is done with caution and the hope that the new kidney begins to produce urine. Volume overloading, especially in the setting of delayed kidney function, is a definite possibility that fortunately occurs in a small number of cases. If this scenario is suspected, keeping the patient intubated, consideration of more invasive monitoring, and dialysis in the postoperative period may be necessary.

LACTATION AND ANESTHESIA Chitra Ramasubbu, MD

BASICS DESCRIPTION

• Every health care organization, based on numerous studies, has found breastfeeding to significantly benefit both the mother and the infant. • Anaesthetists are likely to encounter breastfeeding mothers in their practice, and concerns about the transfer of medications (including local anesthetics, benzodiazepines, opioids, and volatile agents) into breast milk will arise. • There is very limited data regarding the transfer of medications into human milk. Current practice and recommendations are mostly empiric and “common sense.” • The interruption of breastfeeding for long periods is difficult for the infant, uncomfortable for the mother, and may interrupt bonding. • During informed consent, the various modalities, risk of the therapies, effect on the newborn, and possible breastfeeding effects must be discussed. EPIDEMIOLOGY Incidence

• The incidence of surgery during pregnancy ranges from 0.3% to 2.2%. In the US, up to 75,000 pregnant women undergo surgery. • There is limited data regarding the incidence of lactating women undergoing surgery.

Morbidity/Mortality

Neonatal abstinence syndrome may be seen in neonates who have been exposed to intrauterine opioids; more applicable to chronic substance abuse. However this cannot be extrapolated to transfer of opioids from breast milk. PHYSIOLOGY/PATHOPHYSIOLOGY

• The transfer of drugs into milk is determined by the equilibrium forces between the maternal plasma and milk compartment. They include: – Concentration – Half-life of drug – Lipophilicity – Molecular weight • Anesthetic medications: The good majority of drugs used perioperatively have short halflives with rapid redistribution. – Anesthetic agents are rapidly cleared from the maternal plasma within minutes secondary to redistribution to deep tissue compartments, thus minimizing the degree of exposure. – Medications with longer durations of action and active metabolites may have a higher risk to the infant. However, short-term use of these medications is unlikely to produce harmful

effects. – Essentially, it is assumed that if the mother is awake and alert, the medications have left the plasma/milk compartment and have entered the muscle and fat tissue compartments, from which it will be released slowly. • Timing of pumping or breastfeeding in relation to the peaks and troughs of medication has effects on the dose of medication transferred to the milk. Additionally, the amount of milk ingested by the infant affects the amount of drug transfer. • Reduced milk production can occur with aggressive fluid resuscitation. When the plasma oncotic pressure is decreased, breast engorgement can result.

PREVENTATIVE MEASURES

• The early return to breastfeeding is advantageous for both mother and infant. • Consider continuing breastfeeding without any interruptions in the following instances: – Early breastfeeding, when the colostrum volume is small (reduces the amount of drug transfer) – Single doses of medications – Short procedures – Drugs with a short duration of action – Drugs without long-acting active metabolites – Most instances • Consider holding or interrupting breastfeeding in the following instances: – Premature and younger infants; can be more susceptible to small doses of medications. – Infants who are prone to apnea and hypotension; may require interruption of breastfeeding for 12–24 hours.

TREATMENT • Normal term or older infants can resume breastfeeding as soon as the mother is awake, stable, and alert. • A single pumping and discarding of milk after surgery will eliminate any drug retained in milk fat. However, this is seldom necessary and not recommended. • Induction drugs, including propofol, midazolam, etomidate, and thiopental, enter the milk compartment only minimally due to their brief distribution phases. The transport to milk is low to nil. • Anesthetic gases have brief plasma distribution phases, and milk levels are likely nil. However, there are no reports in the literature. • Ketamine use in breastfeeding mothers has not been reported in the literature. Secondary to its side effects of hallucination and dissociative anesthesia, ketamine may not be considered an ideal anesthetic agent in the breastfeeding mother. • Remifentanil may be appropriate for short procedures due to its short duration of action. However, there is no published data to document its effects on fetal sedation. • Diazepam has a long duration of action and consequently transfers into breast milk. The active metabolites have been reported to cause drowsiness in infants. • Midazolam, with a rapid onset of action and metabolic elimination, is preferred for the rapid

induction of anesthesia. The amount of midazolam transferred to an infant via milk is minimal. • Optimal maternal pain control is necessary for initiation and continuation of breastfeeding. For postpartum pain management, non-opioids are preferred. – Acetaminophen at appropriate doses is effective and safe. – Ibuprofen has low-to-nil transfer and is a moderately effective analgesic. – Ketorolac has extremely low transfer into breast milk and is a potent analgesic in mothers without contraindications to it. In the peripartum period, it is frequently used. – Prolonged naproxen use has been associated with GI disturbances in the infant despite low transfer into milk. • Mothers should be encouraged to control pain with the lowest effective dose. High-dose opioid analgesia may affect the infant’s suckling vigor and alertness. – Morphine, in low-to-moderate doses, appears to be reasonably safe in most studies. However, there are variations in the effects of morphine, and some infants are more susceptible to morphine-related sedation than others. – Hydromorphone has been shown to transfer to breast milk. – Hydrocodone and codeine have been safely used in millions of breastfeeding mothers. However, there is no data regarding its transfer through milk. Higher doses may lead to infant sedation. – Fentanyl levels in breast milk have been studied and have been found to be low. – Sufentanil transfer should be similar to fentanyl, even though it has not been published. – Meperidine has a greater incidence and duration of neonatal depression, cyanosis, and bradycardia and should be used minimally. Small doses may be used 1 hour before possible delivery time. When PCA is chosen, morphine and fentanyl are preferred over meperidine. • Local anesthetics: – Bupivacaine enters breast milk in very low doses and in small doses is considered safe. – Parenteral lidocaine infusion for the treatment of arrhythmias was studied in a lactating mother and found to be exceedingly low. – Surgical cases that require large amounts of infiltrated drug, such as plastic surgery, consider pumping and discarding milk for 12 hours before resuming breastfeeding. • Regional anesthesia is preferred over general anesthesia for maternal safety in the peripartum period due to the reduced amount of medications that are globally administered. The same concept may be extrapolated to the breastfeeding mother, and should be considered and discussed. – Minimize local anesthetic dose – Minimize motor blockade – Opioids are commonly added to local anesthetics in both epidurals and spinals for its synergistic effect of producing powerful and longer duration of pain control. Also it reduces the concentration of local anesthetic needed for optimal pain relief, thus reducing motor blockade, hypotension, and overdose reactions. However, there are reports of neonatal sedation and poor suckling following fentanyl epidural anesthesia. – Vasoconstrictors such as epinephrine are used to improve quality of regional block by allowing greater penetration of local anesthetic and reduced diffusion from the epidural

space. Epinephrine may enter breast milk but is rapidly destroyed in the infant’s GI tract prior to absorption. • Atropine use is controversial. Infants are sensitive to anticholinergic agents. Atropine is passed into the milk and may interrupt milk production and produce antimuscarinic effects in infants. There is no data regarding the transfer of glycopyrrolate into milk. However, glycopyrrolate, with its poor lipophilicity and oral bioavailability, is preferred over atropine.

FOLLOW-UP If the mother continues to have difficulty breastfeeding postoperatively, refer to a lactation consultant.

REFERENCES

1. Montgomery A, Hale TW, Academy of Breastfeeding Medicine Protocol Committee. ABM clinical protocol #15: Analgesia and anesthesia for the breastfeeding mother. Breastfeed Med. 2006;1(4):271–277. 2. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001;108(3):776–789. 3. Hale TW. Anesthetic medications in breastfeeding mothers. J Hum Lact. 1999;15(3):185– 194.

ADDITIONAL READING

• Spigset O. Anaesthetic agents and excretion in breast milk. Acta Anaesthesiol Scand. 1994;38(2):94–103. • Zeisler JA, Garder TD, De Mesquita SA. Lidocaine excretion in breast milk. Drug Intell Clin Pharm. 1986;20:691–693.

See Also (Topic, Algorithm, Electronic Media Element) • Substance abuse during pregnancy

CLINICAL PEARLS

• The type of anesthetic depends on the type of surgery and must be tailored to the needs of the individual mother and infant. • The effect of anesthesia on the postpartum mother and infant depends on multiple factors including age of infant, stage of lactation (early or late), and ability of infant to tolerate small quantities of anesthetic medications. • Discontinuing breastfeeding for long periods of time results in suffering for both the nursing infant and mother. • Current opinion is that breastfeeding can be resumed as soon as the mother feels physically and mentally capable to do so and that there is no time interval needed before restarting breastfeeding.

• Limited data and evidence is available and guidelines are lacking.

LAMINAR AIR FLOW Theodore J. Cios, MD, MPH Khaled Sedeek, MD

BASICS DESCRIPTION

• Laminar airflow, also sometimes referred to as streamlined flow, occurs when adjacent layers of a fluid (air, water) slide steadily past each other without disruption. Laminar flow: – Has a pattern that is parallel to the long axis of the tube – Occurs at a lower velocity than the critical velocity – Is dependent upon viscosity (1,2) – Obeys the Hagen–Poiseuille equation – Is more likely to occur at low speeds, small diameters, low densities, and high viscosities • Turbulent flow occurs when flow rates exceed the critical velocity. Turbulent flow: – Has a continuously changing flow pattern (magnitude and direction) and is not linear. It is characterized by irregular fluctuations or mixing of the fluid or gas. The mechanical energy dissipates as heat. – Is dependent upon density (1,2) – Inertial forces overcome viscous forces, and there is not enough viscosity to dissipate motion. – Does not follow the Hagen–Poiseuille equation – Is more likely to occur at high speeds, large diameters, high densities, and low viscosities

PHYSIOLOGY PRINCIPLES

• The Hagen–Poiseuille equation describes the changes in pressure of a non-compressible fluid or gas flowing in a cylindrical tube (1). Changes in pressure are directly related to the fluid viscosity, length of the tube, and flow; it is indirectly related to the radius to the 4th power. ΔP = (8 nLQ) / r4, where ΔP is the pressure gradient, n is the viscosity of the fluid, L is the length of the tube, Q is the flow, and r is the radius. – Viscosity: Can be thought of as the internal/ inherent resistance of a fluid or gas to being deformed. The greater the viscosity, the more energy that is required to move that fluid (e.g., water vs. lava). – Flow through a cylindrical tube: The material in the center of the tube has the greatest velocity, whereas the material adjacent to the walls is stationary due to friction. – Radius: Inversely related to the change in pressure to the 4th power; that is, a small change in the radius of a tube will produce a disproportionate change in pressure. • The Reynolds number quantifies the amount of inertial and viscous forces for specific fluid flow conditions (1). – It is directly related to velocity, density, and diameter; it is inversely related to viscosity. Reynolds number = (vpd)/n, where v is linear velocity, p is the density of the fluid, d is the diameter of the tube, and n is the viscosity of the fluid.

– Increases in fluid viscosity will indirectly decrease the Reynolds value; it is more difficult for viscous lava to move fast enough to attain turbulence. – Turbulent flow results when a critical Reynolds number is reached. Numbers >2,000 make turbulent flow likely (1).

DISEASE/PATHOPHYSIOLOGY

• Asthma: In bronchoconstriction, narrowing the diameter/radius of the bronchiole by smooth muscle contraction creates a sizeable change in the pressure (radius is raised to the 4th power). This creates a transition point in the airflow pattern and can potentially cause turbulence. • Tracheal stenosis: Similar to bronchoconstriction, a decrease in radius creates a transition point in airflow pattern; the increased pressure can result in turbulence. • Atherosclerosis: Deposits can cause abrupt changes in the vessel diameter (decreased radius) that can result in turbulent flow. Additionally, if there is a compensatory increase in vessel diameter distal to the lesion, turbulent flow is more likely to result. • Anemia/polycythemia: In anemic patients, blood is less viscous and has a greater propensity to undergo turbulent flow (inertial forces are greater than viscous forces). The opposite is true for patients with polycythemia and other conditions with higher blood viscosity.

PERIOPERATIVE RELEVANCE

• Anesthetic circuit – Corrugated anesthetic circuit tubing causes turbulent flow to occur at a lower velocity than if tubes were smooth (2,3). Corrugated tubing is designed to allow bending of the hose while preventing twisting and interruption of gas flow. It is less likely to kink and obstruct airflow, especially when making turns or attempting to overcome potentially acute angles. It maintains its diameter during bending (increased Reynold’s number); thus the tubing continues to function well when coiled or bent. – Connector pieces of anesthetic circuits have sharp angles and also increase the likelihood of turbulent flow (2,3). – Endotracheal tube: Flow is laminar, and a small change in diameter will have a profound impact since these 2 parameters are inversely related to the 4th power. Kinking or the presence of secretions will also lead to greater changes in pressure and the development of turbulence. – Applying the Reynolds number equation, the density of a gas has a more significant effect at high flow while viscosity is more significant at low flow. • Cardiovascular system – Vessels: Elastic vessels decrease the tension against the walls and decrease turbulent flow by accommodating changes in flow velocity and changes in diameter that may otherwise alter the Reynolds number. However, large diameters with high velocity tend towards turbulent flow. – At sharp angles/transition points such as arterial bifurcations (carotid, iliac, etc.), previously laminar flow is likely to become turbulent for a period due to changes in the frictional forces encountered. • Respiratory system – Tracheal stenosis: Results in acute constriction of flow by altering the diameter of the

tube, thereby creating transition points proximal and distal to the obstruction at which turbulent flow can occur. May be potentially auscultated over the anterior larynx. – During a resting breathing state (low velocity) airway flow becomes laminar at the level of the bronchioles. However, with exertion (increased velocity), laminar flow may be limited to even smaller airways. • Therapeutic modalities – Helium: Has a lower density than oxygen; thus using high concentrations in a mixture of fresh gas decreases the total density and resistance to flow, with a resultant decrease in the Reynold’s number and potentially turbulence (4). Heliox, a mixture of oxygen and helium, can be useful in certain clinical scenarios such as upper airway obstruction secondary to foreign body, vocal cord dysfunction, respiratory distress, post-extubation stridor, and similar causes (5). – Xenon: An inert gas with a greater density than oxygen can increase turbulence at lower flow rates, when administered as part of a gas mixture. Xenon inhalation can cause a significant increase in peak airway pressure during mechanical ventilation and may limit its use as an anesthetic agent (6,7). – Altitude: At high altitudes, there is lower atmospheric pressure and lower gas density, but little change in viscosity. Consequently, the gas flow through a rotameter will be greater than expected at high flows (turbulence, and more affected by density) but not affected at low flows (laminar, and more influenced by viscosity).

EQUATIONS

• Hagen–Poiseuille equation: ΔP = 8 nLQ/r4, where Q = flow, ΔP = pressure gradient, r = radius, L = length of the tube, n = viscosity of the fluid • Reynolds number = vpd/n, where v = linear velocity, p = density of the fluid, d = diameter of the tube, n = viscosity of the fluid GRAPHS/FIGURES

REFERENCES

1. Young HD, Freedman RA. University physics, 10th ed. Addison-Wesley, 2000. 2. min E. Physics in anesthetic practice, 1st ed., 2003.

3. arbrook GD, Davis PD, Kenny GN. Basic physics and measurement in anaesthesia, 5th ed. Elsevier, 2003. 4. atz IM, Martin AR, Muller PA, et al. The ventilation distribution of helium–oxygen mixtures and the role of inertial losses in the presence of heterogeneous airway obstructions. J Biomech. 2011;44(6):1137–1143.

5. Mihaescu M, Gutmark E, Murugappan S, et al. Modeling flow in a compromised pediatric airway breathing air and heliox. Laryngoscope. 2008;118(12):2205–2211. 6. Rueckoldt H, Vangerow B, Marx G, et al. Xenon inhalation increases airway pressure in ventilated patients. Acta Anaesthesiol Scand. 1999;43:1060–1064. 7. Abramo A, Di Salvo C, Foltran F, et al. Xenon anesthesia improves respiratory gas exchanges in morbidly obese patients. J Obesity. 2010;2010. pii: 421593. Epub 2010 March 2. See Also (Topic, Algorithm, Electronic Media Element) • Asthma • Turbulent flow • Tracheal stenosis

CLINICAL PEARLS

• Heliox is usually 21% oxygen and 79% helium but concentrations of 30% and 70%, respectively, can be used (5). • Using heliox in subglottic pediatric obstruction with in vitro models has been shown to decrease airway resistance by up to 40% (5). • Xenon significantly increases airway pressure and may be of limited use in clinical practice (6,7).

LAPAROSCOPY

Colin Bauer, MD Judith A. Turner, MD, PhD

BASICS DESCRIPTION

• Laparoscopy describes minimally invasive surgical procedures within the chest, abdomen, pelvis, and/or neck. Carbon dioxide (CO2) insufflation expands cavities (e.g.,

pneumoperitoneum [PPN]) to facilitate surgical visualization and intervention. Visualization of joints (arthroscopy) and the bladder (cystoscopy) can be performed with fluid insufflation. • Patient position varies depending on surgery. Common positions include lateral decubitus (nephrectomy), supine (appendectomy), Trendelenburg (prostatectomy), and/or reverse Trendelenburg (gastric bypass). • Generally requires 2–5 incisions for the insertion of multiple ports/trocars; however, some procedures may be performed through a single incision (e.g., appendectomy). • Surgical time varies depending on the patient’s prior surgical history and the specific procedure being performed; simple procedures such as cholecystectomy and appendectomy are generally <1 hour. • Greater than 2 million laparoscopic procedures are performed annually.

PHYSIOLOGY PRINCIPLES

• Insufflation is generally accomplished using a gas, although liquid is used for a small subset of procedures (arthroscopy, cystoscopy). – CO2 is the most commonly used gas for insufflation because it is colorless (enhances

visualization), inexpensive, non-combustible, and highly soluble in blood (decreases risk of a venous air embolism). – Nitrous oxide and oxygen are combustible and are associated with an increased risk of OR fires. – Air and helium have decreased blood solubility and are more likely to cause gas emboli. • Physiologic effect of a pneumoperitoneum: – Cardiac: Decreased preload, increased afterload (secondary to norepinephrine), and decreased cardiac output. Initiation of PPN may be associated with a vagal response and/or asystole; atropine or glycopyrrolate should be immediately available. – Respiratory: Decreased functional residual capacity (FRC), decreased lung compliance, decreased PaO2, and increased peak inspiratory pressures caused by insufflation-induced cephalad migration of the diaphragm and abdominal contents • Trendelenburg or reverse Trendelenburg position is used to improve visualization by using gravity to displace the bowel and other organs from the surgical site. • Physiologic effects of Trendelenburg position:

– Cardiac: Increased venous return and cardiac output. Mitigates some of the adverse cardiac effects of a PPN. – Respiratory: Decreased FRC, lung compliance, and PaO2, and increased peak inspiratory

pressures caused by gravity-induced cephalad displacement of diaphragm and abdominal contents • Physiologic effects of reverse Trendelenburg position: – Cardiac: Decreased venous return (caused by venous pooling in lower extremities) and decreased cardiac output – Respiratory: Increased FRC and pulmonary compliance, and decreased peak inspiratory pressures by facilitating caudal displacement of diaphragm and abdominal contents. Mitigates some of the adverse respiratory effects of a PPN.

DISEASE/PATHOPHYSIOLOGY

• Mortality related to laparoscopy is rare, estimated at 1 in 10,000. • Morbidity associated with laparoscopic procedures usually involves complications related to formation of PPN, physiologic effects of hypercarbia, and/or trocar placement (inadvertent insufflation of a cavity or space other than peritoneum occurs in ~2% of laparoscopic surgeries). • Vagal reflex or asystole with institution of the pneumoperitoneum • CO2 venous embolus: Insertion of a Veress needle or trocar directly into a blood vessel may

lead to a CO2 embolus (associated with a 28% mortality). Manifestations range from

subclinical to hypoxemia, profound hypotension, dysrhythmias, and even cardiac arrest. • Referred shoulder pain from diaphragmatic irritation (C3–5 innervation) • Hypercarbia: CO2 insufflation can lead to hypercarbia if minute ventilation does not

increase proportionately. The ensuing respiratory acidosis can lead to: – Cardiac contractility – Arrhythmias – Pulmonary vasoconstriction – Hyperkalemia – Increased intracranial pressures • Perforation: Placement of Veress needle or trocars can lead to inadvertent organ or blood vessel perforation. – Vascular injury is the most lethal complication (up to 15% mortality); insertion of a Veress needle or trocar into a major blood vessel can cause life-threatening bleeding and is an indication for conversion to an open procedure. • Pneumothorax/pneumomediastinum: – Risk factors include insufflation pressures >15 mm Hg, surgery duration >200 minutes, and congenital or acquired defects in the diaphragm or pleura. – Signs include hypercarbia, increased airway pressure, and hemodynamic instability (tension pneumothorax). – Treatment involves release of the PPN; placement of a chest tube may be necessary in the event of hemodynamic instability. • Subcutaneous emphysema

– Risk factors include malposition of Veress needle in subcutaneous tissue, insufflation pressures >15 mm Hg, and/or surgery duration >200 minutes. – Manifestations include crepitus, increased EtCO2, and respiratory acidosis. PERIOPERATIVE RELEVANCE

• Advantages of laparoscopy: – Improved cosmesis – Shorter recovery time – Decreased pain – Decreased blood loss – Decreased pulmonary complications – Lower incidence of wound infections – Faster recovery of bowel function – Minimizes stress, inflammatory, and metabolic response • Relative contraindications to laparoscopy: – Intracranial hypertension – Hypovolemia – Severe cardiac disease (coronary, valvular, cardiomyopathy) – Severe pulmonary disease (chronic obstructive pulmonary disease, restrictive diseases) – Coagulopathy • Length of hospital stay varies; simple procedures may be performed as outpatient surgeries.

GRAPHS/FIGURES See Table

REFERENCES

1. Gerges FJ, Kanazi GE, Jabbour-khoury SI. Anesthesia for laparoscopy: A review. J Clin Anesth. 2006;18:67–78. 2. Henny CP, Hofland J. Laparoscopic surgery: Pitfalls due to anesthesia, positioning, and pneumoperitoneum. Surg Endosc. 2005;19:1163–1171. 3. Saggar VR, Singhal A, Singh K, et al. Factors influencing development of subcutaneous carbon dioxide emphysema in laparoscopic totally extraperitoneal inguinal hernia repair. J Laparoendosc Adv Surg Tech. 2008;18(2):213–216. 4. Permpongkosol S, Link RE, Su LM, et al. Complications of 2,775 urological laparoscopic procedures: 1993 to 2005. J Urol. 2007;177:580–585. 5. Fuller J, Scott W, Ashar B, et al. Laparoscopic trocar injuries: A report from a U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) Systematic Technology Assessment of Medical Products (STAMP) Committee. November 7, 2003. Available at: http://www.fda.gov/medicaldevices/safety/alertsand notices/ucm197339.htm

ADDITIONAL READING

• Kuczkowski KM. Nonobstetric surgery in the parturient: Anesthetic considerations. J Clin Anesth. 2006;18:5–7. • Manchanda G, Bhalotra AR, Bhadoria P, et al. Capnothorax during laparoscopic cholecystectomy. Indian J Anaesth. 2007;51:231–233. • Takahata O, Kuniswa T, Nagashima M, et al. Effect of age on pulmonary gas exchange during laparoscopy in the Trendelenburg lithotomy position. Acta Anaesthesiol Scand. 2007;51:687–692.

See Also (Topic, Algorithm, Electronic Media Element) • Cystoscopy • Appendectomy • Cholecystectomy • Video-assisted thoracoscopic surgery (VATS)

CLINICAL PEARLS

• Complications of laparoscopy include pneumothorax/pneumomediastinum, hypercarbia, hypotension, subcutaneous emphysema, and/or injury to bowel/ureter/blood vessels or other organs. • Pregnancy considerations: Laparoscopy is the most common surgical procedure performed during the first trimester. General anesthesia for laparoscopy can be safely performed during pregnancy but fetal monitoring should be considered. • Geriatric considerations: EtCO2 is a less reliable estimate of PaCO2 in the elderly. The

baseline increase in alveolar dead space seen in the geriatric patient is exacerbated by laparoscopy and the Trendelenburg position. • Pediatric considerations: Consider using a cuffed endotracheal tube. Increased intraabdominal pressure with a PPN may necessitate increased peak airway pressures.

LARYNGOSCOPY POSITIONING Laura F. Cavallone, MD Davide Cattano, MD, PhD

BASICS DESCRIPTION

There are a number of alternative head and neck positioning techniques that can be performed to improve visualization of the vocal cords during direct laryngoscopy. They include the: • Sniffing position • Neutral “in-line” position • Ramped position • Beach chair position

PHYSIOLOGY PRINCIPLES

• “Sniffing” position is generally thought to be the best position for a patient in preparation for intubation and airway management. Ivan Magill, who first proposed the position and its definition, described it as somebody “sniffing the morning air” or “drinking a pint of beer.” – Main advantages: Optimizes airway patency and facilitates mask ventilation. Provides good exposure of the glottis in most adult subjects and facilitates intubation of the trachea. – Studies have shown conflicting evidence of its efficacy compared to other combinations of extension and flexion of the upper and lower cervical spine and atlanto-occipital joint. Results and conclusions appear to be dependent on the type of population investigated, the endpoints of the studies (easiness of visualization as opposed to easiness of intubation), the experience of the providers, and the type of blades utilized. – Although no univocal conclusion has been reached so far, the sniffing position is most likely a very reasonable “starting point” in preparation for laryngoscopy in the majority of adult patients. Additionally, it may occasionally require adjustments to improve glottis visualization, depending on an individual patient’s variability. • Neutral “in-line” position is the term used to define the cervical spine and head alignment in the natural position assumed while supine. There is no head elevation, cervical spine flexion, or extension. – Main advantages: Provides the best axes alignment for children and infants. Avoids further injury or potential injury in patients with a traumatized cervical spine or at risk for such conditions, respectively. – Disadvantages: Glottis exposure with conventional direct laryngoscopy can be suboptimal in most adults. • “Ramped” position may be achieved by placing blankets or other specifically manufactured devices underneath the upper body and head of the patient. – Main advantages: Facilitated ventilation and visualization of the glottis. Fat tissue at the

level of the neck and chest is favorably displaced by gravity, and can aid with maneuvering the laryngoscope blade and handle. • Beach chair position describes the elevation of the OR bed to 45°. – Main advantages: Offers optimal airway patency in conditions in which there is a risk of airway collapse and obstruction with the patient in the supine position. – Some anaesthetists advocate that even a 25° “back-up” position of the OR bed offers significant improvement of the laryngeal view compared to the classical supine position, and consider this a valuable alternative to the “ramped position.”

ANATOMY

• Sniffing position: Following the observations of Magill, Bannister and Macbeth first studied the angles of the oral, pharyngeal, and laryngeal axes with the head in different positions. Their aim was to identify the best possible alignment of the 3 axes for the purpose of exposing the glottis and facilitating endotracheal tube insertion with direct laryngoscopy. – In the studies by Bannister and Macbeth, the key components to optimal alignment were identified as: Flexion of the lower cervical spine, extension of the upper cervical spine, and extension of the atlanto-occipital joint (same as “sniffing position” of Magill). – The external landmarks used were: The position of the chin, the angle of the mandible with respect to the OR table, and the position of the ears anterior to (or at level with) the sternum. These positions were noted and correlated with optimal exposure of the glottis (Figure 1). Although in reality the perfect alignment of these axes does not seem to be achieved, as shown in recent MRI studies, this still seems to be the position that offers the best approximation to the illustrated “ideal alignment.”

FIGURE 1. “Sniffing position (1).”

• Neutral position: There is no elevation of the head compared to the rest of the body, and the cervical spine rests in its natural position without being flexed or extended. In this position the oral, pharyngeal, and laryngeal axes are not aligned.

FIGURE 2. Neutral “in-line” position. There are 3 distinct axes (1).

• Ramped position: The presence of a “wedge” underneath the upper body of the patient creates a horizontal alignment between the external auditory meatus and the sternal notch. The aim is to achieve in obese patients the same “best alignment” of the 3 axes (oral, pharyngeal, and laryngeal) that is reached with the sniffing position in nonobese patients.

FIGURE 3. Ramped position (1).

• Beach chair position: The patient’s head is in line with the anesthesia provider’s xiphoid process. In this position airway patency is maintained better than in the supine position and access to the airway by the anesthesia provider is still relatively easy. The provider may be on a step and at an angle of the backrest to facilitate direct laryngoscopy and manual bagmask ventilation.

FIGURE 4. Beach chair position (1).

DISEASE/PATHOPHYSIOLOGY

• The presence of medical conditions that alter the patient’s anatomy and/or the body habitus may significantly influence the choice of the appropriate position to secure the airway. – Obese patients may benefit from a “ramped,” “beach chair,” or other “back-up” position to optimize glottis exposure. – Known or suspected cervical spine injury patients are at risk of spinal cord lesions if positioned in the “sniffing position.” Neutral position with “in-line” manual stabilization techniques and/or awake fiberoptic technique is recommended for these patients. – In rheumatoid arthritis patients, anterior atlantoaxial subluxation and displacement or fracture of the odontoid process may occur in the “sniffing position.” Extreme caution is recommended with any movement of the cervical spine during intubation. – Scoliosis and previous cervical spine surgery may alter neck mobility and prevent optimal positioning for laryngoscopy. – Conditions affecting the ability of the patient to maintain airway patency, such as the presence of extrinsic or intrinsic obstruction of the upper airway, may require the use of alternative techniques for intubation (e.g., fiberoptic-assisted intubation in the sitting or beach chair position with the patient spontaneously breathing).

Pediatric Considerations

• In infants and small children, the prominence of the occiput in relation to the body results in slight neck flexion when the child is supine, and, according to some experts, head elevation is not required to obtain optimal positioning for direct laryngoscopy. • Moderate head flexion may facilitate nasotracheal intubation in infants and young children. • Overall there is substantial lack of agreement among experts on the best position for direct laryngoscopy in young children. • Down syndrome and other congenital syndromes associated with craniofacial anomalies require special attention in planning for laryngoscopy and intubation.

PERIOPERATIVE RELEVANCE

• The choice of one specific position over another may have a critical impact on intubation success rate and/or maintenance of adequate oxygenation while managing the airway. It is critical to identify patients who may require airway management in the ramped, beach chair, or “back-up” position (high risk of airway obstruction in the supine position) and patients who require “in-line” stabilization in the neutral position (unstable cervical spine). It is also important to be able to recognize anatomical anomalies/changes that may require adjustments of the head and neck position in order to obtain better access to the airway for intubation and/or ventilation. While no predefined formula exists to help in any given condition, attention to this matter and careful consideration of alternative positioning is an important component of a successful strategy for airway management. • Non-pathological modifications of the body habitus must not be disregarded when planning for direct laryngoscopy positioning. Certain hairdos may affect the possibility to appropriately extend the superior cervical spine and the atlanto-occipital joint (e.g., large mass of thick hair pulled up at the back of the head or hair that is worked into firm braids).

REFERENCES

1. Illustration by Cavallone L, MD.

2. Greenland KB, Eley V, Edwards MJ, et al. The origins of the sniffing position and the Three Axes Alignment Theory for direct laryngoscopy. Anaesth Intensive Care. 2008;36(Suppl 1):23–27. 3. Lee BJ, Kang JM, Kim DO. Laryngeal exposure during laryngoscopy is better in the 25° back-up position than in the supine position. Br J Anaesth. 2007;99(4):581–586.

4. Rao SL, Kunselman AR, Schuler HG, et al. Laryngoscopy and tracheal intubation in the head-elevated position in obese patients: A randomized, controlled, equivalence trial. Anesth Analg. 2008;107(6):1912–1918. 5. Fox WT, Harris S, Kennedy NJ. Prevalence of difficult intubation in a bariatric population, using the beach chair position. Anaesthesia. 2008;63(12):1339–1342.

6. Vialet R, Nau A. Effect of head posture on pediatric oropharyngeal structures: Implications for airway management in infants and children. Curr Opin Anaesthesiol. 2009;22(3):396– 399. See Also (Topic, Algorithm, Electronic Media Element) • Difficult airway • Functional residual capacity • Esophageal intubation

CLINICAL PEARLS

• Correctly positioning a patient on the OR bed prior to induction of general anesthesia and in preparation for laryngoscopy is a fundamental part of preoperative planning and one of the determinants of success at managing the airway. • It is critical to utilize the appropriate position for each patient and for each intubating device. • For example, video-laryngoscopes that have a side tube channel to guide ETT insertion through the glottis appear to have increased success with an “in-line” (neutral) neck position compared to a “sniffing position.” Additionally, it has been suggested that these devices may present a higher rate of success and less cervical movement during intubation in conditions that require in-line manual stabilization compared to a Macintosh blade. • Optimal pre-oxygenation also depends on patient positioning. Pre-oxygenation in the headup position seems more efficacious than pre-oxygenation in the supine position since it improves the functional residual capacity. • While the “sniffing” analogy has been used for almost a century, other analogies, such as “win with the chin” with reference to the best position for winning a foot race (Brindley 2010), have been proposed and considered effective in teaching basic positioning for laryngoscopy to novices.

LARYNGOSPASM

Pascal O. Owusu-Agyemang, MD

BASICS DESCRIPTION

• Laryngospasm is a protective reflex closure of the glottis as a result of abnormal stimulus (1) [B]. • Perioperatively this can result in airway obstruction with resultant desaturation. EPIDEMIOLOGY Incidence

• The overall incidence of laryngospasm is 0.87% (2)[C]. • The incidence ranges from 1.74% in children aged 9 years old to 2.82% in infants (2)[C].

Prevalence

• Increased in children • More frequent during emergence from anesthesia • Tonsillectomies and adenoidectomies have the highest incidence of post-extubation laryngospasm.

Morbidity

• Oxygen desaturation • Anoxic brain injury • Negative pressure pulmonary edema • Bradycardia • Pulmonary aspiration • Cardiac arrest

Mortality

Although laryngospasm has been quoted as a preceding cause of airway obstruction and ultimately death, the exact incidence of mortality is unknown. ETIOLOGY/RISK FACTORS

• Insufficient depth of anesthesia • Young age • Airway irritation (blood/secretions, regurgitation) • Airway manipulation • Upper respiratory tract infections • Smokers • Passive smoke exposure • Type of surgery (e.g., tonsillectomy and adenoidectomy)

PHYSIOLOGY/PATHOPHYSIOLOGY

• Afferent fibers of the superior laryngeal nerve control laryngeal muscle contractions which protect the airway during swallowing. • Laryngospasm occurs when there is loss of inhibition of the laryngeal closure reflex as a result of abnormal excitation (3)[A]. This commonly occurs during induction and upon emergence from anesthesia. The patient is particularly vulnerable during the second stage of anesthesia. The presence of saliva, mucus secretions, and airway devices (endotracheal tube, trumpets) can elicit abnormal excitation and can lead to laryngospasm. • It is important to note that laryngospasm is mediated by skeletal muscle while bronchospasm is smooth muscle mediated. • Laryngospasm is characterized by the prolonged interruption of respiration due to a ball valve mechanism of the vocal cords, false cords, and supraglottic tissue.

PREVENTATIVE MEASURES

• Topical lidocaine can blunt the airway response to irritation and instrumentation. • If mask induction is performed, sevoflurane or halothane should be used as these 2 agents are the least irritating to the airway. • Desflurane is very irritating to the unprotected airway and should be avoided during mask inductions. • If IV line insertion is performed after a mask induction, it should be done after deep anesthesia has been achieved. • The use of an adequate dose of muscle relaxants will minimize the chances of laryngospasm during intubation. An appropriate amount of time should be allowed for full onset. • Suctioning of the oropharynx before emergence (stage 2) from anesthesia • Antisialagogues (to reduce secretions) may be considered. • Avoid painful stimulation during emergence.

DIAGNOSIS • Laryngospasm can be characterized as partial or complete. • Partial laryngospasm is generally associated with an audible inspiratory or expiratory sound of airway obstruction. • As the obstruction becomes worse, tracheal tug and paradoxical respiratory movements of the chest and abdomen will develop. • Should laryngospasm progress from partial to complete, the audible signs cease, leaving only visible signs of airway obstruction. • Oxyhemoglobin desaturation, cyanosis, bradycardia, and subsequently cardiac arrest may follow if the symptoms are not treated promptly.

DIFFERENTIAL DIAGNOSIS

• Supraglottic obstruction: This is usually relieved by performing a jaw thrust, chin lift, and insertion of an oropharyngeal airway (2)[C]. • Bronchospasm: This is characterized by wheezing on auscultation and diminished breath sounds (2)[C].

TREATMENT • Partial laryngospasm – CPAP with 100% oxygen and a tight-fitting mask can help facilitate ventilation and/or deepen the level of anesthesia • Complete laryngospasm – CPAP will not break complete laryngospasm because forced inflation of the pharynx distends the piriform fossa on either side of the larynx and presses the aryepiglottic folds more firmly against each other. Oxygen will fill the stomach instead of the lungs. – In the absence of an IV line, perform continuous positive airway pressure (CPAP) with 100% oxygen, optimize airway with a jaw thrust and chin lift, and deepen anesthesia with an inhalational agent (preferably sevoflurane or halothane). If these measures fail, administer succinylcholine 4 mg/kg intramuscularly. – In addition to IV propofol, airway optimization should be performed. This should be done by performing a jaw thrust and chin lift maneuver. This will stretch the geniohyoid muscle to partially open the larynx and allow for ventilation and further deepening of anesthesia with inhalational agents. – If the above measures fail a muscle relaxant may be given to relax the vocal cords. Succinylcholine 0.1 mg/kg allows for quick onset and recovery. – Emergence even after treatment with succinylcholine. It is therefore important to eliminate contributing noxious stimuli before attempting another emergence. – In the presence of an IV line, complete laryngospasm should be treated by deepening anesthesia with propofol (0.25–0.8 mg/kg) (1)[B].

Pediatric Considerations

• Succinylcholine administration in children may be associated with severe bradycardia and cardiac arrest; thus, it is highly recommended to give atropine (0.02 mg/kg) with succinylcholine. • Gentle chest compression with 100% oxygen in children. 3 theories for efficacy: – Vocal cord spasm prevents entrance of air into the lung, but not its exit; thus, chest compression “pushes” air in the lung directly on the vocal cords to relieve the spasm. It functions to deliver positive pressure, but from the “opposite” direction of CPAP. – Second, chest compression stimulates fast, shallow breathing with or without increases in minute ventilation. This results in an increased respiratory drive. – Third, the Hering–Breuer deflation reflex mediated via the vagus nerve is activated by stimulation of stretch receptors or stimulation of proprioceptors activated by lung deflation. Thus, vocal cord relaxation may result from vagal nerve impulses. – Benefits over CPAP include not distending the stomach or splinting of the diaphragm (4) [A]. • Magnesium: Doses of 15 mg/kg over 20 minutes appeared to significantly decrease the incidence of laryngospasm in pediatric patients (5).

FOLLOW-UP

• Patients without immediate, apparent complications should be observed for 2–3 hours and then discharged. • Negative pressure pulmonary edema can occur after laryngospasm. This is the result of decreased intrathoracic pressure generated by an attempted inspiration against a closed glottis. This creates a mean negative transpulmonary pressure, leading to transudation of fluid from the pulmonary capillaries into the interstitial space. – The clinical signs are oxygen desaturation, pink frothy sputum in the airway, or signs of alveolar infiltration on CXR. – Treatment is directed at supplementation of oxygen and diuretics. Occasionally, patients may require reintubation to facilitate adequate oxygenation. • Patients who develop cardiopulmonary complications including negative pressure pulmonary edema should be admitted for further care.

CLOSED CLAIMS DATA

• A review of the malpractice database from 1973 to 2000 revealed that airway obstruction including laryngospasm (n = 8) was the most common respiratory event. • Another review of the Pediatric Perioperative Cardiac Arrest Registry from 1998 to 2004 determined that causes accounted for 27% of all cardiac arrest episodes and that airway obstruction from laryngospasm was the most common cause (6%).

REFERENCES

1. Al-alami AA, Zestos MM, Baraka AS. Pediatric laryngospasm: Prevention and treatment. Curr Opin Anaesthesiol. 2009;22(3):388–395. 2. Alalami AA, Ayoub CM, Baraka AS. Laryngospasm: Review of different prevention and treatment modalities. Paediatr Anaesth. 2008;18(4):281–288. 3. Burgoyne LL, Anghelescu DL. Intervention steps for treating laryngospasm in pediatric patients. Paediatr Anaesth. 2008;18(4):297–302. 4. Al-Metwalli RR, Mowafi HA, Ismail SA. Gentle chest compression relieves extubation laryngospasm in children. J Anesth. 2010;24:854–857. 5. Gulhas N, Durmus M, Demirbilek S, et al. The use of magnesium to prevent laryngospasm after tonsillectomy and adenoidectomy: A preliminary study. Paediatr Anaesth. 2003;13(1):43–47.

ADDITIONAL READING

• Olsson GL, Hallen B. Laryngospasm during anaesthesia: A computer-aided incidence study in 136,929 patients. Acta Anaesthesiol Scand. 1984;28(5):567–575.

See Also (Topic, Algorithm, Electronic Media Element) • Superior laryngeal nerve

CODES

ICD9

478.75 Laryngeal spasm ICD10

J38.5 Laryngeal spasm

CLINICAL PEARLS

• Laryngospasm results in obstruction of the larynx and may lead to desaturation, postobstructive pulmonary edema, bradycardia, and cardiac arrest. • The incidence is highest in children and during emergence from anesthesia. • For partial laryngospasm, the initial treatment typically consists of CPAP and 100% oxygen, combined with a jaw thrust maneuver. If unsuccessful, propofol and muscle relaxants may be required to relax the vocal cords.

LATEX ALLERGY

Marc A. Logarta, MD, DABA, FANZCA

BASICS DESCRIPTION

• Allergy to latex manifests as a variety of clinical symptoms and is often categorized into Type IV and Type I hypersensitivity reactions. • Type IV hypersensitivity is a cell-mediated or delayed type reaction. It is often localized to the area of contact and occurs 48–72 hours after exposure. Often referred to as allergic contact dermatitis, T-cell-mediated allergy, or chemical allergy. • Type I hypersensitivity is IgE-mediated and results in an immediate response. It is systemic and ranges from contact urticaria to occupational rhinoconjunctivitis, asthma, or anaphylaxis. • Latex is the second most common cause of anaphylaxis in the operating room. Under general anesthesia it presents as cardiovascular compromise, airway swelling and obstruction, flushing, and edema. EPIDEMIOLOGY Incidence

• Sensitivity to latex has been increasing in prominence since the introduction of Universal Precautions. • Life-threatening reactions in the US occur in approximately 1 in 30,000–50,000 people undergoing general anesthesia. Prevalence

• General population in the US (sensitization or allergy): 1–2% • Healthcare workers: 3–14% • Rubber industry workers: 10% • Spina bifida and congenital urogenital anomalies: 24–60%

Morbidity/Mortality

Anaphylactic reactions under anesthesia have a mortality of 3.4%. ETIOLOGY/RISK FACTORS

• Anaphylactoid reaction • Repeated exposure to latex over time (repeated bladder catheterizations, spinal bifida patients, multiple surgeries, especially laparotomies) • Occupational exposure to latex (healthcare workers, latex factory workers) • Urticaria • Asthma • Rhinitis

• Spina bifida patients • Atopic patients • Female preponderance • Cross-reactivity with allergies to a variety of fruits (bananas, avocadoes, mangoes, watermelons) and chestnuts

PHYSIOLOGY/PATHOPHYSIOLOGY

• Raw latex is the milky sap from the rubber tree (Hevea brasiliensis), to which ammonia is added as the main preservative. • Type I hypersensitivity is an IgE-mediated reaction to natural rubber latex antigen. It can manifest as mild to life-threatening symptoms that include contact urticaria, occupational rhinoconjunctivitis, asthma, or anaphylaxis. – Latex sensitization occurs when exposure (airborne, parenteral, mucosal routes) to latex antigen induces CD4+ and T cells to produce IL-4, IL-5, IL-6, IL-10, granulocytemacrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF). These cytokines and mediators result in the production of IgE antibody specific to latex antigen. – Upon re-exposure (airborne, parenteral, mucosal routes) to latex antigen, there is a crosslinkage of IgE molecules by latex on the surface of mast cells. This results in mast cell degranulation and the release of mediators such as histamine, tryptase, slow-reacting substance-A (SRS-A), prostaglandin, and leukotrienes. – These mediators increase mucous secretion, capillary permeability, bronchial smooth muscle tone (H1 receptor activation bradykinin), as well as decrease arterial tone (H2 receptor activation). Manifests as bronchospasm, V/Q mismatch, hypoxemia, and hypotension. – Activation of Hageman factor can start a cascade of disseminated intravascular coagulation. – Transudation of fluid into the extravascular space can lead to a clinical hypovolemia which may result in myocardial ischemia. • Type IV hypersensitivity is a contact dermatitis reaction to chemicals used to process rubber by Langerhans and T cells. The patient presents within 48–72 hours of exposure with erythema, vesicles, scaling, hyperpigmentation, and lichenification of the contacted areas. • Irritant contact dermatitis is not a latex allergy; it is, however, the most common reaction associated with latex, and is not life-threatening. It results from various alkaline chemicals added during rubber production. The dermatitis appears within minutes to hours as a localized abrasion with pruritus, erythema, cracking, dryness, and chapping of the skin.

PREVENTATIVE MEASURES

• Prevention of exposure to latex in known latex-sensitized patients is the keystone to preventing a potentially life-threatening allergic reaction. A latex-safe protocol in each institution should be in place and should consist of identification of patients at risk, establishment of a latex-free environment, and close coordination between all staff involved in the management of these patients. • Absolute avoidance of any latex-containing products is essential throughout the perioperative period and during the hospital stay. Anesthetic equipments that may contain latex include gloves, some syringe plungers, Foley catheters, medication vials with rubber

stoppers, disposable anesthesia bags, bandages (adhesives), tourniquets, some endotracheal tubes, bellows, IV ports, blood pressure cuffs, some face masks. All manufacturer packaging should indicate the presence of latex in any medical grade product. • Preoperative prophylaxis with corticosteroids and antihistamines is controversial. At best, it may attenuate a reaction but will not prevent true anaphylaxis. • Latex-sensitive patients should be scheduled as first cases because the quantity of latex aeroallergens is likely to be the lowest early in the morning. Airborne latex antigen can be suspended in the air for up to 5 hours after a case. • A latex-free cart should be used that contains non-latex alternatives, and all latex gloves and products should be removed from the operating room. The room should also be labeled as latex-free. • A resuscitation cart should be placed adjacent to the operating room. • The American Academy of Allergy and Immunology recommends that clinical testing should be offered to high-risk patients in a latex-free environment.

DIAGNOSIS • Signs and symptoms depend on the type, route, and amount of latex exposure as well as the individual’s sensitivity. – Awake patients may manifest swelling of contact areas, hives/welts, sneezing, runny nose, ocular redness and tears, sore throat, GI cramping, wheezing, shortness of breath, and chest tightness. Respiratory manifestations include bilateral rales, stridor, and cyanosis. – Anesthetized patients may have a more dubious presentation. Dermatologic symptoms (hives, welts, flushing, swelling) may not be immediately recognized under drapes and warming devices. Hypotension is the first presenting sign in approximately 1/3rd of patients in anaphylactic shock. Additionally, respiratory manifestations such as bilateral rales, may not be immediately recognized. • Monitors – Noninvasive blood pressure monitoring: Look for worsening hypotension over a few minutes, although some patients will present with a more precipitous decline in blood pressure. – EKG: Tachycardia, dysrhythmias, ST changes; pulseless electrical activity may be the first manifestation in anaphylactic shock. – Airway pressure monitors: High peak and plateau inspiratory pressures may be seen in the mechanically ventilated patient. If the bronchospasm is severe, the patient may also have auto-PEEP which will further contribute to hypotension. Decreased pulmonary compliance may not be immediately recognized with LMAs. – End-tidal carbon dioxide: May be increased with upsloping of capnograph tracing. It should be noted that complete airway obstruction may occur with a supraglottic device, mask GA, or supplemental oxygen modality (nasal canula, face mask) for a sedation case; this will result in the extinguishment of the capnograph tracing. – Pulmonary artery catheter (PAC) or pulse contour cardiac output monitoring (PiCCO): If present, a low systemic vascular resistance will be present. • Serum tryptase levels should be sent at the time of the event, at 1 hour, and 6–24 hours

after the episode. • Serologic testing: Carries no risk of anaphylaxis and is the test of choice if the history reveals a high probability of allergic reaction. – Radioallergent absorbent testing (RAST) is capable of measuring the level of drug-specific IgE antibody in the serum. It is highly specific (80–87%), but has a low sensitivity (50– 60%); false-negatives occur 25% of the time. • Skin testing: Carries the risk of inducing systemic anaphylaxis and should only be performed by physicians with training and resources to respond to an emergency situation. – Skin prick testing uses an antigen solution at a variety of dilutions. It has been found to be very sensitive and specific. – Intradermal testing uses an antigen solution. – Patch testing may be useful in establishing the diagnosis of contact dermatitis (Type IV allergic reaction).

DIFFERENTIAL DIAGNOSIS

• Anaphylaxis due to other antigens (neuromuscular blocking agents, antibiotics, protamine, blood transfusions): • Asthma • Angioedema • Cardiogenic shock • Septic shock • Carcinoid syndrome • Pulmonary embolism

TREATMENT • Management of anaphylaxis due to latex does not differ from any other type of anaphylactic reaction. • Discontinue the exposure to latex. • Communicate the emergency situation with the operating room team. • Administer 100% oxygen; maintain a clear airway with a low threshold for intubation. • Administration of epinephrine 10–100 μg IV • Inhaled bronchodilators may be necessary. • IV crystalloid fluid as clinically indicated • Diphenhydramine 50–75 mg IV • Hydrocortisone up to 200 mg IV or methylprednisolone 1–2 mg/kg • Consideration of sodium bicarbonate if severe acidosis persists • Consider central line placement for monitoring and therapy if not already in place.

FOLLOW-UP • After an episode of anaphylaxis, the patient should be closely monitored in an ICU setting since symptoms can recur in up to 20% of patients. • If the patient experienced their first allergic reaction, then they should be referred to an

allergist or dermatologist for further testing. They should also be fully informed of the situation and wear a Medic-Alert bracelet indicating their allergy. • If no episode of anaphylaxis occurred in a latex-sensitive patient, they can likely be discharged to the ward with continued latex precautions.

REFERENCES

1. Hepner DL, Castells MC. Latex allergy: An update. Anesth Analg. 2003;96:1219–1229.

2. Kam PC, Thompson JF. Latex allergy: An emerging health hazard for operating theatre staff. Anaesthesia. 1997;84(3):570–575. 3. Farley CA, Jones HM. Latex allergy. Contin Educ Anaesth Crit Care Pain. 2002;2(1):20–23. 4. Ryder SA. Anaphylaxis. Contin Educ Anaesth Crit Care Pain. 2004;4(4):111–113.

ADDITIONAL READING

• American latex allergy association

See Also (Topic, Algorithm, Electronic Media Element) • Anaphylaxis • Asthma • ETCO2

CODES ICD9 V15.07 Allergy to latex ICD10 Z91.040 Latex allergy status

CLINICAL PEARLS

• Latex allergies have increased since the introduction of Universal Precautions in the healthcare setting. • Known latex allergies allow the operating room team to make preparations to avoid a potentially life-threatening reaction. In addition to absolute avoidance of latex-containing products, patients should be scheduled as first cases since aeroallergens can be suspended in the air for up to 5 hours. • Unknown allergies pose the greatest threat since signs and symptoms are not specific to latex anaphylaxis and may also be delayed. Dermatologic signs may not be immediately obvious under surgical drapes and cardiovascular collapse (hypotension, PEA) may be the first presenting symptom. Furthermore, inadequate circulation may delay dermatologic manifestations. • Latex antigens are found in several products in the operating room and should be well

known to the anaesthetist. Additionally, the anaesthetist is responsible for clearing out items specific to their care (disposable anesthesia bag, tourniquets, syringe plungers, medication vials with rubber stoppers, and some face masks, ETTs, etc.).

LEFT BUNDLE BRANCH BLOCK Davinder Singh, MD Jennifer Scovotti, MA Aman Mahajan, MD, PhD

BASICS DESCRIPTION

• A left bundle branch block (LBBB) occurs when transmission of a cardiac electrical impulse is delayed across the main left bundle branch or both the anterior and posterior fascicles. • The left bundle branch originates at the crest of the muscular ventricular septum and descends inferiorly along the left ventricular septal surface. It branches into 3 major fascicles: – Anterior – Posterior – Central (proceeds to the midseptal region) EPIDEMIOLOGY Incidence

• LBB affects 1% of the general population. • Occurs in up to 30% of patients with heart failure. • May occur in 20% of patients after aortic valve replacement.

Prevalence

Increases with age:

• Age 50 years, affects 0.4% of people • Age 75 years, affects 2.3% • Age 80 years, affects 5.7%

Morbidity

• Outcome is excellent in younger subjects while older patients (mean = 62 years old) have shown an increased risk for coronary disease and heart failure (20–30% incidence of each). • Patients also have an increased risk (1% per year) for progression to AV block.

Mortality

• Independent predictor of mortality in patients with known or suspected coronary artery disease • The cumulative cardiovascular disease mortality rate is 3–4 times greater than the general population. ETIOLOGY/RISK FACTORS LBBB can result from:

• Coronary artery disease • Left ventricular hypertrophy • Cardiomyopathy • Hypertension • Myocardial infarction • Ventricular septal defect repair • Septal myectomy • Aortic valve surgery • Neuromuscular and sclerodegenerative diseases • Benign condition

PATHOPHYSIOLOGY

Impaired transmission of the left bundle’s electrical impulse is associated with:

• Asynchronous left ventricular activation that reduces the efficiency of left ventricular contraction • Sequential activation of the left and right ventricles (rather than simultaneous); this can lead to wall motion abnormalities. • Shortened duration of diastolic flow that can disturb coronary perfusion

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Concern for complete heart block if the procedure involves intracardiac manipulation (e.g., right heart catheterization, PA catheter placement). There is a 2–5% chance of complete heart block with PA catheter placement. • A retrospective study has shown that asymptomatic LBBB patients undergoing noncardiac surgery do not have a higher incidence of cardiac complications, but did suggest that they may have more difficulty tolerating increased stress from noncardiac complications such as sepsis. • In patients who have heart failure from dilated cardiomyopathy and bundle branch block, resynchronization pacing has become an important component to therapy.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Often clinically silent • Some patients experience exercise intolerance, presyncope, and syncope.

History

• Patients with isolated LBBB are usually asymptomatic; however, history of syncope is concerning for occult coronary artery disease, impaired ventricular function, or higher level conduction disturbance and should be thoroughly investigated. • Assess for concurrent cardiac disease

Signs/Physical Exam

Auscultatory findings include an absent or diminished first heart sound and reversed splitting

of the second heart sound (S2 is split in expiration and single in inspiration). TREATMENT HISTORY

Resynchronization therapy may be performed in patients with dilated cardiomyopathy, a history of syncopal episodes, or for other underlying cardiac disease. MEDICATIONS

• No medications are routinely used for treatment. • Class I (including lidocaine) and III antiarrhythmic agents (including amiodarone and sotalol) can delay conduction in the His-Purkinje system and should be avoided. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• LBBB can be seen on an EKG tracing, and the electrical patterns show where the block is located. • EKG criteria includes: – QRS duration ≥120 ms – Broad notched R wave in leads I, aVL, V5, V6 – P and T waves usually opposite in direction to QRS • SVT may be mistaken for ventricular tachycardia in patients with LBBB because of the wide QRS. CONCOMITANT ORGAN DYSFUNCTION

LBBB is often a marker for 1 of 4 underlying conditions:

• Coronary artery disease • Hypertensive heart disease • Aortic valve disease • Cardiomyopathy

CIRCUMSTANCES TO DELAY/CONDITIONS

• New onset of LBBB during anesthesia (most often during hypertensive or tachycardic episodes) has been shown to be a sign of myocardial ischemia. • Abnormal electrolytes; hypokalemia, hypomagnesemia, and hypocalcemia delay repolarization and should be corrected. CLASSIFICATIONS

• LBBB has been defined as homophasic (concordant: cLBBB) or heterophasic (discordant: dLBBB) when associated with a positive or negative T wave in leads I and V5-V6, respectively. • In systolic heart failure, dLBBB is associated with a worse clinical, neurohormonal, and prognostic profile. • There are also partial blocks of the left bundle branch: “Left anterior fascicular block” (LAFB) and a “left posterior fascicular block” (LPFB).

TREATMENT PREOPERATIVE PREPARATION Premedications

Consider preoperative sedation when appropriate. Limiting anxiety and sympathetic outflow is crucial as tachycardia can induce LBBB. Special Concerns for Informed Consent None

INTRAOPERATIVE CARE Choice of Anesthesia

• Whether general or regional is chosen, operative management should focus on prevention of excessive sympathetic activity and avoidance of factors that cause tachycardia. • There is no evidence that general or regional anesthesia is safer than the other. • Ketamine should be used cautiously due to its ability to cause tachycardia.

Monitors

• LBBB prevents diagnosis of ischemia with EKG because ST and T wave changes are already present, and therefore more invasive monitoring may be required depending on operative risk factors. • Temporary pacing should be available, and pacing pads should be placed for any cardiac procedure. Induction/Airway Management

• Sympathetic outflow caused by laryngoscopy, intubation, suctioning, and cold inspired gases should be attenuated by short-acting opioids and/or esmolol. • Lidocaine, despite being used without complications, is a class Ib antiarrhythmic agent and can theoretically worsen conduction and left ventricular dyssynchrony. Maintenance

• Avoid factors that increase sympathetic activity and maintain normocarbia, normothermia, normoglycemia, normovolemia, and normoxia. • Patients should also be kept adequately anesthetized to prevent sympathetic outflow from innocuous stimuli. Extubation/Emergence

Consider a “deep” extubation while the patient remains in a surgical plane of anesthesia to decrease sympathetic outflow.

POSTOPERATIVE CARE BED ACUITY

LBBB patients may have less ability to tolerate stressful states and warrant close clinical and

laboratory monitoring.

MEDICATIONS/LAB STUDIES/CONSULTS

Maintain a low threshold for a myocardial ischemia workup given the unreliability of an EKG. COMPLICATIONS

• Complete heart block • Failure to detect cardiac ischemia • Sudden cardiac death

GRAPHS/FIGURES

FIGURE 1. Left bundle branch block (LBBB). On the left, a homophasic LBBB is shown and named for its accompanying

positive T wave (also known as concordant LBBB). On the right, a heterophasic LBBB is shown and named for its accompanying negative T wave (also known as discordant LBBB).

REFERENCES

1. Hesse B, Diaz LA, Snader CE, et al. Complete bundle branch block as an independent predictor of all-cause mortality: Report of 7,073 patients referred for nuclear exercise testing. Am J Med. 2001;110(4):253–259. 2. Rotman M, Triebwasser JH. A clinical and follow-up study of right and left bundle branch block. Circulation. 1975;51(3):477–484.

3. Imanishi R, Seto S, Ichimaru S, et al. Prognostic significance of incident complete left bundle branch block observed over a 40-year period. Am J Cardiol. 2006;98(5):644–648. 4. Dorman T, Breslow MJ, Pronovost PJ, et al. Bundle-branch block as a risk factor in noncardiac surgery. Arch Intern Med. 2000;160(8): 1149–1152. 5. Schneider JF, Thomas HE Jr, Sorlie P, et al. Comparative features of newly acquired left and right bundle branch block in the general population: The Framingham study. Am J Cardiol. 1981;47(4):931–940. 6. Keefe DL, Griffin JC, Harrison DC, et al. Atrioventricular conduction abnormalities in patients undergoing isolated aortic or mitral valve replacement. Pacing Clin Electrophysiol. 1985;8(3 Pt 1):393–398.

ADDITIONAL READING

• Stoelting R, Hines R, Marschall K. Stoelting’s anesthesia and co-existing disease, 5th ed. Philadelphia, PA: Churchill Livingstone, 2008:77–79. • Wagner GS, Macfarlane P, Wellens H, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram. Part VI: Acute ischemia/infarction. A scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol. 2009;53(11):1003–1011.

See Also (Topic, Algorithm, Electronic Media Element) • Right bundle branch block • Coronary artery disease • 12-lead Electrocardiogram

CODES ICD9 426.3 Other left bundle branch block ICD10 I44.7 Left bundle-branch block, unspecified

CLINICAL PEARLS

• LBBB patients often have significant comorbidities; it is associated with cardiovascular disease in older patients. Additionally, patients may not be able to handle cardiovascular stress as well. • LBBB prevents detection of ischemia by EKG. • There is a concern for complete heart block if procedures involve intracardiac manipulation.

LEFT VENTRICULAR END DIASTOLIC PRESSURE (LVEDP) Sumit Singh, MD Aman Mahajan, MD, PhD

BASICS DESCRIPTION

• Left ventricular end-diastolic pressure (LVEDP) is defined as the pressure in the ventricles at the end of diastole. The measurement is used in clinical practice as a means to approximate the left ventricular end-diastolic volume (LVEDV) or preload (LVEDP ∼ LVEDV). • LVEDP can be ideally determined by left ventricular catheterization in the catheterization laboratory. It is measured at the Z-point, the point on the left ventricular pressure trace where the slope of the ventricular pressure upstroke changes (approximately 50 ms after the EKG Q wave, and generally coincides with the R wave) (1).

FIGURE 1. The LVEDP is measured at the Z point. It is the point on the ventricular pressure upstroke where the slope changes. It occurs approximately 50 ms after the Q wave and usually corresponds with the R wave.

• In most clinical situations, LVEDP is determined by Swan Ganz catheterization, by floating a balloon-tipped catheter into the pulmonary artery. Although it does not enter the left ventricle, when the balloon is inflated (wedged), it isolates the catheter tip and brings it in continuity with the blood column in the left atrium and LV during end diastole. – Measurements: The pulmonary artery wedge pressure (PAWP) is equal to the LVEDP, given that there is no mitral valve pathology and the pulmonary artery catheter is in the West zone 3 of the lung (where pulmonary artery pressure > pulmonary venous pressure > pulmonary alveolar pressure).

– Waveforms: Left atrial tracings are similar to central venous pressure (CVP) tracing from the right atrium, with “a”, “c”, and “v” waves.

PHYSIOLOGY PRINCIPLES

• During an ideal ventricular diastole, the pressures in all cardiac chambers equilibrate: CVP = RVEDP = PADP = PAWP = LAP = LVEDP; where CVP is central venous pressure, RVEDP is right ventricular end diastolic pressure, PADP is pulmonary artery diastolic pressure, PAWP is pulmonary artery wedge pressure, and LAP is left atrial pressure. • Frank Starling principle states that the force of cardiac contraction is directly proportional to end-diastolic muscle fiber length at any given level of intrinsic contractility or inotropy. – Increasing the venous return of the left ventricle increases the volume and preload and thereby LVEDP (increases stroke volume). – Flat portion of diastolic filling: A significant increase in filling volume or preload results in a small increase in filling pressure. – Steep portion of diastolic filling: In comparison, there is a significant increase in filling pressure with the same volume towards the end of diastole. – Left-shifting describes abnormal decreases in compliance (e.g., sepsis, shock, myocardial ischemia, or fibrotic chambers). Additionally, there is a paradoxical increase in filling pressures with a decrease in filling volume.

FIGURE 2. The ventricular diastolic pressure-volume relationship forms a curvilinear line and the slope reflects wall compliance. Compliance is dynamic and changes with chamber volume, thus affecting the ability of using the LVEDP to approximate the LVEDV. Curve A represents normal compliance. Curve B represents a right shift or increased compliance, as can occur with dilated cardiomyopathy, where a change in the volume (x) results in a smaller increase in pressure.

FIGURE 3. Frank Starling curve. Changes in venous return correlate to changes in LVEDP/LVEDV that affect the stroke volume (SV). The inotropic state affects the stroke volume at a given preload (dashes–higher inotropy, dots–decreased inotropy).

ANATOMY

• PAWP is taken at the pulmonary artery (distal tip of pulmonary artery catheter) with the balloon inflated and occluding the branch of the pulmonary artery. • The ability of proximal pressures (CVP, PAWP, etc.) to accurately reflect the LVEDP is dependent on unobstructed continuity of blood flow during diastole. Any anatomical or physiological condition that impairs this will result in inaccurate downstream pressure estimation.

DISEASE/PATHOPHYSIOLOGY

• Conditions in which PAWP underestimates LVEDP: – Decreased left ventricular compliance (e.g., MI, LVH). The mean left atrial pressure (LAP) is less than LVEDP, and there is an increased end-diastolic “a” wave. – Aortic regurgitation (AR): The mitral valve closes before the end of diastole due to run-off from the aorta (LAP < LVEDP). – Pulmonary regurgitation: Bidirectional run-off of the pulmonary artery flow (PADP < LVEDP). – Decreased pulmonary vascular bed • Conditions in which PAWP overestimates LVEDP: – Positive end-expiratory pressure (PEEP): The pulmonary artery catheter may become lodged in lung zone 1 or 2. Pulmonary venous pressure readings are actually lower than airway pressure, leading to a falsely elevated PAWP. – Pulmonary hypertension: Increases in the pulmonary vascular resistance will record a higher PADP which does not reflect left ventricular pressures (PADP > mPAWP). – Mitral stenosis: There is obstruction to the flow of blood through the mitral valve, which results in a higher mean LAP and thereby overestimation of the LVEDP. – Mitral regurgitation: A retrograde systolic “v” wave or regurgitant systolic flow raises the mean atrial pressure. • Increased compliance. In dilated cardiomyopathy, the left ventricle is very dilated without any appreciable increase in ventricular wall thickness. This will result in increased compliance and even though the LVEDV may be very high, the corresponding LVEDP elevation might not be significant.

PERIOPERATIVE RELEVANCE

• Elevated LVEDP is an independent risk factor of mortality in cardiac surgery, independent of left ventricular ejection fraction (2,3). • Atrial kick: Normally provides 20% contribution to the LVEDV. In LVH, this may increase to 50% and the “a” wave may be prominent and provide a better estimate of LVEDP than PAWP (4). • Mitral valve: Both stenosis and regurgitation can overestimate the LVEDP. • Perioperative presentation of cardiogenic versus hypovolemic shock can be differentiated by using the LVEDP (CVP/PAWP) as a surrogate marker of preload. A low CVP, or PAWP, is

consistent with hypovolemia, and a high CVP/PAWP would indicate cardiogenic shock (e.g., MI, CHF). This can be clinically important in deciding when to give fluids versus other interventions. – The goal of all-fluid resuscitation is to increase preload and “recruit” stroke volume to increase end-organ perfusion, as per the Starling mechanism. – Markers of LVEDP (CVP/PAWP) can be trended over time with improvement or worsening of cardiac output. – Clinically, signs of increased cardiac output changes would relate to increased urine output, decreased capillary refill time, improvement in mental status and blood pressure. – Other more sophisticated monitors which can measure cardiac output changes with preload changes are esophageal Doppler monitor, echocardiography, and systolic pressure variations. • Myocardial compliance: PAWP measurements are dependent on myocardial compliance. Multiple studies on ICU patients have shown the failure of PAWP in acute illness to correlate with LVEDV (5). • Clinical use: CVP or PAWP alone is rarely used to guide therapy. In situations of shock, after the patient has been given IV fluids to raise the CVP to around 12 mm Hg (adequate preload), without improvement in blood pressure or cardiac output, other methods of assessment such as bedside echocardiography may be used for cardiac assessment. – The American Society of Anesthesiologist Practice Guidelines recommends PAC for highrisk surgical patients only (6). – Suggested clinical indications for monitoring LVEDV and LVEDP are severe sepsis and trauma, high-risk cardiac surgery, pulmonary hypertension, abdominal compartment syndrome, and therapy with PEEP.

REFERENCES

1. Braunwald E, Fishman AP, Cournand A. Time relationship of dynamic events in the cardiac chambers, pulmonary artery and aorta in man. Circ Res. 1956;4:100–107. 2. Salem R, Denault AY, Couture P, et al. Left ventricular end-diastolic pressure is a predictor of mortality in cardiac surgery independently of left ventricular ejection fraction. Br J Anaesth. 2006;97:292–297. 3. Apostolakis EE, Baikoussis NG, Parissis H, et al. Left ventricular diastolic dysfunction of the cardiac surgery patient: A point of view for the cardiac surgeon and cardioanesthesiologist. J Cardiothorac Surg. 2009;4:67. 4. Falicov RE, Resnekov L. Relationship of the pulmonary artery end-diastolic pressure to the left ventricular end-diastolic and mean filling pressures in patients with and without left ventricular dysfunction. Circulation. 1970;42:65–73. 5. Fontes ML, Bellows W, Ngo L, et al. Assessment of ventricular function in critically ill patients: Limitations of pulmonary artery catheterization. Institutions of the McSPI Research Group. J Cardiothorac Vasc Anesth. 1999;13:521–527. 6. American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Practice guidelines for pulmonary artery catheterization: An updated report. Anesthesiology. 2003;99:988–1014.

ADDITIONAL READING

• Miller RD. Miller’s anesthesia, 7th ed. Philadelphia: Churchill Livingstone, 2009.

See Also (Topic, Algorithm, Electronic Media Element) • Cardiac output • Mitral stenosis • Mitral regurgitation • Left ventricular hypertrophy • Dilated cardiomyopathy • Positive end expiratory pressure (PEEP)

CLINICAL PEARLS

• LVEDP (pressure) is a surrogate measurement for LVEDV (volume). • The assumption that the pulmonary artery catheter is in continuity with the left ventricle during diastole is only valid when the catheter is in the West zone 3 of the lungs (e.g., where the pulmonary venous pressure is greater than the airway pressure). • In using CVP and PAWP as a marker of LVEDP, it is important to be aware of the caveats of interpreting the readings. Any situation which anatomically or physiologically interrupts the continuity of blood in the heart during diastole will alter the CVP or PAWP readings. Conditions, such as mitral stenosis or regurgitation, pulmonary regurgitation, and aortic regurgitation, will all cause an overestimation or underestimation of the LVEDP by the CVP and PAWP. • The pressure volume curve in the heart is curvilinear and shifts to the right with increased LV compliance or the left with decreased compliance.

LIVER FUNCTION TESTS Jason Han Chua, MD Anahat Dhillon, MD

BASICS DESCRIPTION

• “Liver function tests” (LFTs) is the common vernacular for the standard biochemistry profile provided by most laboratories. It typically includes: – Aspartate aminotransferase (AST or SGOT) – Alanine aminotransferase (ALT or SGPT) – Alkaline phosphatase – Bilirubin (total, unconjugated, conjugated) – Albumin • LFTs are more accurately described as tests of overall liver health (metabolic and synthetic function) or inflammation (necrosis). • True, specific tests of liver function (galactose clearance, aminopyrine clearance) are not widely used. PHYSIOLOGY PRINCIPLES

• Aspartate transaminase (also known as serum glutamic oxaloacetic transaminase [SGOT]) is an enzyme found in liver parenchymal cells, brain, heart, kidneys, muscle, and red blood cells. It is responsible for transferring the aspartate amino group to ketoglutaric acid. Elevated levels may indicate tissue damage or inflammation. • Alanine aminotransferase (also known as serum glutamic pyruvic transaminase [SGPT]) is an enzyme found primarily in liver parenchymal cells and, to a lesser extent, in the heart, kidneys, and muscle. It is responsible for transferring the alanine amino group to ketoglutaric acid. Values provide a measure of hepatic damage or inflammation and are considered more specific than AST values. • Alkaline phosphatase is an enzyme that catalyzes hydrolysis of phosphate esters at an alkaline pH. More than 80% is found in the liver and bone; minor sites include the placenta, intestine, and kidney. Measurements indicate inflammation, particularly in the biliary tract. • Bilirubin is the byproduct of heme catabolism. When hemoglobin is released from red blood cells (normal breakdown, damaged or old cells), the globin is turned into amino acids. In reticuloendothelial cells, the heme is converted into unconjugated bilirubin which is waterinsoluble and binds to albumin. The liver conjugates it with glucuronic acid to form conjugated bilirubin, which is water-soluble. Bilirubin values can, thus, provide a measure of hepatic metabolic function. • Albumin is synthesized by the liver and comprises 60% of plasma proteins. It has a serum half-life of approximately 20 days. Measurements indicate hepatic synthetic function, but do not necessarily reflect acute processes. Normal adult values: 3.4–5.4 g/dL. PHYSIOLOGY/PATHOPHYSIOLOGY

• As many as 1/3rd of patients screened may have a nonspecific abnormality in LFTs. Incidence of clinically significant disease is ∼1%. • Differential diagnosis can be broken down into: – Hepatocellular inflammation or dysfunction: Inflammation and necrosis of hepatocytes result in the release of AST and ALT (e.g., hepatitis A). Normal levels of AST and ALT do not fall within a Gaussian distribution. Instead, distribution is skewed rightward, meaning levels up to 1.5 the upper limits of “normal” do not necessarily suggest liver disease. Hepatic dysfunction results in decreased metabolic and/or synthetic function. – Cholestatic disease: Includes intrahepatic and extrahepatic processes and is usually accompanied by an elevation in bilirubin (direct or indirect) and/or alkaline phosphatase. – Infiltrative disease such as amyloidosis can result in the release of AST and ALT as well as decreased metabolic and synthetic function. • Clinical history is important to help differentiate between causes: – Family history is relevant since many genetic disorders can affect liver function (Gilbert’s and Dubin Johnson, Wilson’s disease, etc.). – Sexual and social history, travel, and work exposure can also point to causes such as viral hepatitis. – Systemic conditions affecting LFTs include cardiac disease, inflammatory bowel disease, diabetes, arthritis, hypogonadism, and thyroid disease. • Transaminases: – Since AST is less specific for liver disease, an isolated elevation can suggest cardiac or muscular disease. – An elevated AST/ALT ratio >2 is more likely to be associated with alcoholic hepatitis. When it is <1.0 it is more likely to be associated with viral hepatitis. – In acute liver injury (choledocholithiasis, uncomplicated viral hepatitis, ischemic hepatitis), transaminase elevation can be severe, but often resolves within days to weeks. Normalization usually indicates improvement; however, rapid decreases may suggest profound worsening and cell death. – Non-alcoholic steatohepatitis, non-alcoholic fatty liver, obesity, and thyroid disease can lead to elevated transaminases with or without significant disease. – Pharmacologic causes include acetaminophen (potentiated with alcohol consumption), NSAIDs, ACE inhibitors, nicotinic acid, and many antibiotics and antifungals. • Alkaline phosphatase: – Obstruction of bile ducts leads to increased bile duct epithelial production of alkaline phosphatase (can occur with obstruction of small ducts without clinically significant cholestasis). – Cholestasis may be diffuse (intrahepatic cholestasis), extrahepatic (gallstones or tumors), localized (cancer), or multifocal (granulomatous disease). – Cholestasis can be differentiated from osteolytic disease either by fractionation for hepatic alkaline phosphatase or by testing gamma glutamyl transferase levels (increase when hepatic in origin). – Other causes of elevation include hyperthyroidism, heart failure, and lymphoma. – When elevated disproportionately to hyperbilirubinemia, may be due to granulomatous or infiltrative liver disease (sarcoid, fungal infection, tuberculosis, lymphoma) or early

primary biliary sclerosis or primary sclerosing cholangitis. – Pitfalls: Must be performed while fasting Parturients and children have baseline elevated levels (2–3 times normal). May indicate excessive alcohol consumption • Bilirubin: – A greater than 80% fraction of unconjugated bilirubin suggests hemolysis or Gilbert’s syndrome. – A greater than 50% fraction of conjugated bilirubin suggests hepatocellular dysfunction or cholestasis. • Albumin: – Can be decreased in severe systemic disease, liver disease >3 weeks duration, or in rapidly progressive liver disease, where albumin is consumed rapidly – Lower in parturients – In the absence of other liver test abnormalities, low albumin is usually due to non-hepatic causes such as proteinuria or malnutrition. • Prothrombin time: – Measures activity of vitamin K-dependent clotting factors which are synthesized in the liver – Cholestasis prevents absorption of vitamin K; hepatocellular disease prevents synthesis of factors. • Miscellaneous: – IgM, ANA: Elevated in autoimmune disease – Low serum copper, uric acid, and ceruloplasmin indicate Wilson’s disease. – Transferrin saturation >60% suggests hemochromatosis.

PERIOPERATIVE RELEVANCE

• Preoperative LFTs can aid with diagnosing disease/hepatic insults and assessing severity. • Associated disease: – Infectious diseases (Hepatitis B, C): Care must be taken to minimize practitioner exposure. – Hepatorenal syndrome: Renal failure associated with hepatic failure. May be reversible or irreversible. Increased morbidity/mortality due to risk of fungemia, uremia, etc. – Hepatopulmonary syndrome: Elevated pulmonary arterial pressure and increased extracardiac shunting leading to hypoxemia • Severity-dependent considerations: – Encephalopathy: Increased risk in the presence of portocaval shunt – Ascites, increased intra-abdominal pressure: Increased risk of aspiration and desaturation – Coagulopathy: Transfusion may be indicated in procedures that may not otherwise require blood; patients requiring transfusion are more prone to citrate toxicity. – Vasoplegia, low SVR: Higher cardiac output required to maintain blood pressure • Postoperative abnormal LFTs can occur in up to 25–75% of patients without liver disease, and mild elevations are considered typical. Postoperative jaundice typically presents within 2 weeks following surgery and is unusual in patients without liver disease. It is commonly the result of a combination of hypotension, hypoxemia, pigment overload, and sepsis.

EQUATIONS

Child-Pugh score: • Class A = 0–1 point, good prognosis • Class B = 2–4 points • Class C = ≥5 points, limited life expectancy Table 1 Relevant Child-Pugh Scores

REFERENCE

1. Faust TW, Reddy KR. Postoperative jaundice. Clin Liver Dis. 2004;8:151–166.

2. Kamath PS. Clinical approach to the patient with abnormal liver test results. Mayo Clin Proc. 1996;71:1089–1096.

3. Kaplan MM. Laboratory tests. In: Schiff L, Schiff ER, eds. Diseases of the liver, 7th ed. Philadelphia, PA: Lippincott, 1993:108–144. 4. Quinn PG, Johnston DE. Detection of chronic liver disease: Costs and benefits. Gastroenterologist. 1997;5:58–77. See Also (Topic, Algorithm, Electronic Media Element) • Postoperative jaundice • End-stage liver disease • Prothrombin time

CLINICAL PEARLS

• Of the routine LFTs, only albumin, bilirubin, and PT are actual indicators of liver function. • Patients with cirrhosis can have “normal LFTs.” • Mildly elevated ALT can be due to normal age and gender variability or muscle injury.

LIVER RESECTION Michelle Braunfeld, MD

BASICS DESCRIPTION General

• Liver resections are performed to remove diseased liver parenchyma: Tumors (primary and secondary), cysts, and adenomas. It is not suitable for severely cirrhotic livers because of the risk of postoperative hepatic failure. • Outcome and, hence, the decision to resect, are dependent on the location, number, and distribution of the mass, as well as the amount of liver that will remain. The liver has significant reserve capacity that allows a large portion to be excised. Additionally, it has the capability to regenerate; occasionally portal vein embolization may be performed to facilitate this. • Modalities prior to resection: – Tumor shrinkage may be achieved with chemotherapy; it can either be systemic or directed. Intra-arterial therapies can be utilized to decrease whole-body adverse effects. It involves threading a catheter through the femoral artery in the groin to the feeding vessels. – Radiofrequency ablation (RFA): May be performed percutaneously with the aid of imaging modalities or direct visualization during open procedures (or laparoscopic surgery). The tip of a needle probe is heated utilizing alternating electric current to destroy tumors. Alternatively, microwave ablation may be performed, particularly for tumors near largediameter vessels. – Portal vein embolization: Blood vessels to the tumor are embolized, and nutrients and flow are diverted to the other side with the goal of facilitating growth/regeneration. Repeat imaging to assess hypertrophy is recommended 3–4 weeks after embolization. • Following dissection, hepatic resection is either: – Anatomic: Margins defined by segmental liver anatomy – Non-anatomic: Margins defined by tumor • Surgical maneuvers to decrease bleeding include portal triad clamping (Pringle’s maneuver) and selective hepatic venous occlusion. Pringle’s maneuver is generally without hemodynamic consequence to the patient. Hepatic tolerance of this maneuver is enhanced by intermittent clamping for 15 minutes followed by unclamping for 5 minutes. Selective hepatic venous occlusion (occlusion of the hepatic venous branches without caval compromise) has been shown to be as effective as a low CVP (central venous pressure) technique for reducing blood loss in patients who are unable to tolerate a CVP <5 mm Hg (1). • Laparoscopic resection may or may not be hand-assisted. Transection is accomplished via repeated, layered application of endovascular staplers.

Position

Supine, bilateral upper extremities abducted to <90% Incision

Bilateral subcostal incisions ± midline extension Approximate Time

1.5–5 hours depending on the extent of resection EBL Expected

100–1,500 mL, depending on extent of resection and use of cell saver Hospital Stay 3–10 days

Special Equipment for Surgery • Ultrasonic dissector • Vascular stapler • Tissue sealer

EPIDEMIOLOGY Incidence

• 7,000 resections performed in 2004 (2) • 18,920 new cases of hepatic/biliary cancer in US in 2004

Prevalence

Liver cancer is considered a “rare disease” by the National Institutes of Health (NIH); there are <200,000 cases in the US. Morbidity

23–56% depending on the extent of resection, and indication for surgery (3)

Mortality

2.6% among high-volume centers (3)

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Establish adequate venous access; large fluid shifts can occur in additional to massive hemorrhage from hepatic vessels. • Maximize patient warming measures. • Help minimize blood loss by maintaining a low CVP (<5 mm Hg). • Minimize transfusion with techniques such as preoperative autologous donation, cell saver, or isovolemic hemodilution.

PREOPERATIVE ASSESSMENT

SYMPTOMS

• Usually asymptomatic. Often tumor is discovered as a result of metastatic workup or preventive surveillance. • May occasionally present with abdominal pain

History

• Resection candidates are usually screened for significant hepatic dysfunction. • Liver cancer is commonly a metastatic disease from the colon.

Signs/Physical Exam

May have stigmata of cirrhosis and/or portal hypertension MEDICATIONS

• Chemotherapy for primary tumor: Commonly utilized agents include 5-flurouracil, oxaliplatin, and cetuximab. • Antiviral medications for chronic viral hepatitis

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Standard labs are dictated by age and comorbidities. • In chronic hepatic disease, use the INR, creatinine, and bilirubin values to calculate the MELD score. CONCOMITANT ORGAN DYSFUNCTION

May have organ system dysfunction secondary to cirrhosis or portal hypertension

TREATMENT PREOPERATIVE PREPARATION Premedications

No absolute contraindications. Titrate carefully in the presence of known underlying hepatic dysfunction, especially benzodiazepines. Special Concerns for Informed Consent

• Epidural catheter placement for postoperative pain • Potential need for invasive monitors such as arterial or central line • Blood consent

Antibiotics/Common Organisms

• Biliary penetration/concentration requires Gram-negative coverage. • Ceftriaxone, ampicillin/sulbactam, and piperacillin/tazobactam can provide broader Gramnegative coverage.

INTRAOPERATIVE CARE

Choice of Anesthesia

• General endotracheal anesthesia • Regional techniques for postoperative pain management are acceptable in patients with normal preoperative coagulation parameters. Postoperative coagulopathy correlates with the extent of resection and blood loss. INR peaks on POD #1, ranging from a mean of 1.3 in left lateral segmentectomy to 1.6 in right hepatic lobectomy. Platelet count nadir is POD #3, with a mean of 110–160 K in hepatic lobectomy (major resection). Thus, although continuous epidural analgesia can be used for postoperative pain, the catheter will remain in place for a few days (generally 2–5) until coagulation abnormalities have corrected (ASRA recommendation: INR <1.5) (4,5).

Monitors

• Standard ASA monitors • Consider arterial line for larger procedures (e.g., hepatic lobectomy). • Consider central line placement for larger procedures. There is literature to support the use of peripheral venous pressures (PVP) in lieu of CVP for monitoring (6,7).

Induction/Airway Management

Consider a rapid sequence or modified rapid sequence induction in patients with portal hypertension. Maintenance

• Minimize and avoid agents that require hepatic metabolism to terminate their effects, if possible. • Consider cisatracurium if hepatic function is a concern. • Isoflurane has an excellent track record; however, sevoflurane and desflurane are also acceptable. • Maintain a CVP <5 mm Hg until parenchymal division is complete, if possible. This can minimize blood loss; the liver has multiple caval communications and elevated caval pressures cause increased back-bleeding from the hepatic surface (8). • Temperature: Implement warming measures early; hypothermia contributes to coagulopathy.

Extubation/Emergence

Plan to extubate, unless there were large fluid shifts or blood loss during the surgery

POSTOPERATIVE CARE BED ACUITY

• Varies according to extent of resection, degree of underlying disease • Pulmonary issues: Upper abdominal surgery lasting 3–5 hours places patients at high risk for postoperative pulmonary complications. The rate of complications also correlates with the extent of resection and intraoperative blood transfusion.

ANALGESIA

• Patient-controlled analgesia • Indwelling epidural catheters for postoperative analgesia are not contraindicated. However, the INR may increase immediately postoperatively along with decreases in platelet count (depending on the amount resected and underlying liver parenchymal disease).

COMPLICATIONS

• Bleeding • Bile leak • Hepatic failure: Primarily avoided by careful patient selection, preservation of adequate remnant volume, and judicious use of Pringle’s maneuver. Postoperative causes include sepsis, cholestasis, portal venous thrombosis, or remnant size/portal flow mismatch (9).

PROGNOSIS

Survival varies according to the extent of resection and underlying liver parenchymal disease.

REFERENCES

1. Smyrniotis V, Kostopanagiotou G, Theodoraki K, et al. The role of central venous pressure and type of vascular control in blood loss during major liver resections. Am J Surg. 2004;187(3):398–402. 2. Dimick JB, Cowan JA Jr, Knol JA, et al. Hepatic resection in the United States. Arch Surg. 2003;138(2):185–191. 3. Virani S, Michaelson JS, Hutter MM, et al. Morbidity and mortality after liver resection: Results of the patient safety in surgery study. J Am Coll Surg. 2007;10(3):1284–1292. 4. Schumann R, Zabala L, Angelis M, et al. Altered hematologic profiles following donor right hepatectomy and implications for perioperative analgesic management. Liver Transpl. 2004;10(3):363–368. 5. Matot I, Scheinin O, Eid A, et al. Epidural anesthesia and analgesia in liver resection. Anesth Analg. 2002;95:1179–1181. 6. Amar D, Melendez JA, Zhang H, et al. Correlation of peripheral venous pressure and central venous pressure in surgical patients. J Cardiothorac Vasc Anesth. 2001;15(1):40– 43.

7. Stéphan F, Rezaiguia-Delclaux S. Usefulness of a central venous catheter during hepatic surgery. Acta Anaesthesiol Scand. 2008;52(3):388–396. 8. Melendez JA, Arslan V, Fischer ME, et al. Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: Blood loss, blood transfusion, and the risk of postoperative renal dysfunction. J Am Coll Surg. 1998;187(6):620–625. 9. Garcea G, Maddern GJ. Liver failure after major hepatic resection. J Hepatobiliary Pancreat Surg. 2009;16:145–155. See Also (Topic, Algorithm, Electronic Media Element) • Liver transplant • Cirrhosis

• Hypothermia • Postoperative pulmonary complications

CLINICAL PEARLS

• The extent of tolerable resection is inversely proportional to the degree of underlying hepatic parenchymal disease. • Maintain a low CVP <5 mm Hg, particularly during parenchymal division to reduce blood loss. • Complex coagulopathy is associated with large resections, with immediate increase in INR. • Continuous epidural analgesia for postoperative pain management is not contraindicated. Be aware that the epidural may need to be kept in place for several days postoperatively, and that there is a risk of bleeding complications if it is displaced before coagulation function has recovered.

LIVER TRANSPLANTATION Cynthia Wang, MD Michelle Braunfeld, MD

BASICS DESCRIPTION General

• Orthotopic or heterotopic liver transplantation is the definitive treatment of choice for endstage liver disease. The first successful liver transplant was performed by Dr. Thomas Starzl in 1963. • Following incision, the liver is dissected free, and major ligamentous connections are skeletonized (common bile duct, hepatic artery and vein, portal vein). These structures are then ligated, and the suprahepatic and infrahepatic vena cava are clamped followed by removal of the diseased liver. • The donor allograft is placed into the patient’s abdomen, and anastomoses are created between the donor and recipient suprahepatic vena cava, infrahepatic vena cava, and portal vein. The liver is then reperfused by unclamping the anastomoses. • Following reperfusion of the organ, the hepatic artery anastomosis is completed, as well as the bile duct, either to the patient’s native bile duct or to the small bowel (Roux-en-Y). • In the piggyback technique, the donor hepatic vein is anastomosed end-to-side to the recipient’s vena cava, preserving the recipient cava. Position

Supine with bilateral upper extremities abducted <90° Incision

Upper abdominal inverse T incision Approximate Time

4–12 hours, depending on patient complexity and surgical difficulty EBL Expected

• Can range from <500 mL to multiple times the patient’s total blood volume in extreme cases. The average is 1,500–3,000 mL. • Blood loss and transfusion requirements are generally higher in patients with higher MELD scores. Hospital Stay

1–3 weeks postoperatively; may be longer depending on patient complexity and surgical difficulty Special Equipment for Surgery

• Rapid infuser +/– cell saver • For complex patients, consider veno-venous bypass (may need perfusionist) and intraoperative dialysis (may need additional personnel).

EPIDEMIOLOGY Incidence

• In 2008, there were 11,176 new registrants on the liver transplant waiting list (candidates may register at multiple centers); there were 6,069 liver transplant recipients. In 2010, there were 5,246 liver transplant recipients.

Morbidity

• Highly variable depending on patient complexity at the time of transplantation, coexisting disease, and complications post-transplantation • Increased with high MELD scores, morbid obesity, concomitant cardiopulmonary disease and/or renal disease, postoperative rejection, and biliary complications

Mortality

• Patient survival rates: – 3 months 94.3% – 1 year 88.4% – 5 years 73.8% – 10 years 60.0%

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients presenting for liver transplantation must be evaluated thoroughly for multisystemic ramifications of end-stage liver disease as well as concomitant disease unrelated to underlying liver disease that may affect perioperative management. • Anesthetic agents may have altered pharmacokinetics and pharmacodynamics (increased volume of distribution, decreased clearance, and increased sensitivity). • Veno-venous bypass (VVB) may be used in patients who may not hemodynamically tolerate caval clamping. VVB involves cannulating the portal and femoral veins and returning the circulation to the axillary or subclavian veins through a bypass circuit. This maintains venous return to the heart and decompresses splanchnic venous congestion.

PREOPERATIVE ASSESSMENT SYMPTOMS

• CV: Palpitations, episodes of lightheadedness or fainting due to overall decreased systemic vascular resistance, decreased functional capacity • Renal system: Polyuria, oliguria, or anuria • GI system: Hematochezia, melena, hematemesis • Hematologic system: Easy bleeding/bruising • Skin/other: Jaundice, itching, weakness, fatigue, anorexia, weight loss

History

Etiology and course of disease Signs/Physical Exam

• CNS: Altered mental status, asterixis • CV: Decreased blood pressure, possible increased jugular venous pressure if fluid overload or right heart insufficiency due to worsening pulmonary hypertension • Pulmonary system: Hypoxia/hypoxemia, clubbing, decreased breath sounds due to effusion, rales due to pulmonary edema • GI system: Palpable liver edge, ascites, splenomegaly, GI bleeding due to esophageal varices and hemorrhoids • Skin/joints: Jaundice, icterus, fetor hepaticus

MEDICATIONS

• Furosemide, spironolactone, bumetanide, hydrochlorothiazide • Lactulose, rifaximin • Cholestyramine, colestipol • Vitamin K • Propranolol • Midodrine, octreotide • Interferon for viral hepatitis • Corticosteroids for autoimmune hepatitis • Penicillamine for Wilson disease

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC: Anemia, thrombocytopenia, leukopenia or elevated white blood cell count • Chemistry panel: Hyponatremia, hypo- or hyperkalemia, hypocalcemia, hypomagnesemia, hypoglycemia, acidosis, serum creatinine >1.5 mg/dL in hepatorenal syndrome (HRS) • Coagulation panel: Increased PT/PTT/INR, hypofibrinogenemia • Aminotransferases: Elevated, AST > ALT • Alkaline phosphatase: Usually elevated • Bilirubin: Increasingly elevated with progression of liver failure • ECG, echocardiography, chemical or nuclear stress test to assess for areas of reversible ischemia, possible cardiac catheterization to assess for CAD and more accurate measurement of intracardiac and pulmonary pressures • CXR to evaluate for edema or effusions • Pulmonary function tests (if indicated) • CT scan to evaluate for possible metastases in cases of hepatocellular carcinoma

CONCOMITANT ORGAN DYSFUNCTION

• CNS: Hepatic encephalopathy, cerebral edema in patients with acute liver failure leading to increased ICP • Cardiovascular system: Hyperdynamic circulation; cirrhotic cardiomyopathy characterized by systolic and diastolic dysfunction and electrophysiologic abnormalities; may have coexisting CAD or valvular disease

• Pulmonary system: Hepatopulmonary syndrome (HPS), portopulmonary hypertension, restrictive lung disease due to ascites, pleural effusions • Renal system: HRS characterized the absence of primary renal disease, proteinuria, hypovolemia, and/or evidence of ATN; renal tubular acidosis; tacrolimus/cyclosporineassociated renal insufficiency • GI system: Portal hypertension, ascites, delayed gastric emptying, portal hypertensive gastropathy • Hematologic system: Thrombocytopathia and predisposition to disseminated intravascular coagulation (DIC), hyper- and hypofibrinolysis • Electrolyte abnormalities

TREATMENT PREOPERATIVE PREPARATION Premedications

Careful premedication at the discretion of the managing physician. May avoid premedication if signs of encephalopathy, potentially difficult airway, or high risk of aspiration. Special Concerns for Informed Consent

May have to be obtained from a designated health care proxy if the patient is encephalopathic or incapacitated Antibiotics/Common Organisms

• Need good penetration/concentration in bile • Commonly, ceftriaxone, cefotaxime, ampicillin/sulbactam. Often avoid vancomycin due to prevalence of vancomycin-resistant Enterococcus. INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia; regional for postoperative analgesia is contraindicated Monitors

• Standard ASA monitors • Direct arterial blood pressure monitor • Central venous line and pressure monitoring • Additional monitors depend on patient comorbidities and institutional practices and provider (surgeon, anaesthetist) preference – Pulmonary artery catheter with capability of measuring the CO/CI – BIS monitor – TEE – Thromboelastogram (TEG) • ICP monitor in patients with cerebral edema (i.e., acute liver failure patients); alternate monitoring options when intracranial ICP monitoring is not available include transcranial Doppler, cerebral oximetry, BIS, and EEG monitoring.

Induction/Airway Management

• Rapid sequence or modified rapid sequence induction to reduce the risk of aspiration • Use of induction agents that optimize hemodynamic stability • Gentle laryngoscopy in the coagulopathic patient

Maintenance

• Traditionally, isoflurane is used due to its ability to preserve splanchnic blood flow. In patients with cerebral edema, may consider total IV anesthesia or only minimal doses of volatile agents to decrease the degree of cerebral vasodilation. • Long-acting narcotics; cisatracurium may be preferred due to its metabolism independent of liver function if extubation in the OR is planned. • Pre-anhepatic phase: Aggressive fluid resuscitation in preparation for caval clamping; maintain hemodynamic stability; optimize coagulopathy to facilitate surgical exposure and hepatectomy • Anhepatic phase: Monitor acid–base status and electrolytes; attempt to maintain normothermia in preparation for reperfusion • Reperfusion: Quickly treat hypotension, acidosis, and dysrhythmias; correct hyperkalemia and hypothermia • Neohepatic phase: Maintain hemodynamic stability in order to ensure perfusion to the newly grafted liver; correct coagulopathy; monitor for fibrinolysis and DIC; watch for evidence of liver function/primary graft nonfunction • Optional therapies: Antifibrinolytics, mannitol, furosemide, THAM, sodium bicarbonate, insulin, methylene blue, dextrose

Extubation/Emergence

Most often, patients remain intubated and are extubated later in the ICU. In rare instances, if the intraoperative course was very straightforward, extubation in the OR may be considered. Return of neuromuscular function and adequate analgesia must be achieved prior to extubation.

POSTOPERATIVE CARE BED ACUITY ICU

ANALGESIA IV PCA

COMPLICATIONS

• Primary graft nonfunction: Within minutes to hours, often requires urgent re-transplantation • Acute rejection: Occurs within days to weeks • Chronic rejection: Occurs after 1 year • Hepatic artery thrombosis (HAT) • Bile duct stricture, biliary leak • Bleeding, infection

PROGNOSIS

• Highly variable depending on comorbidities and perioperative hospital course • Graft survival rates (cadaveric): 3 months 91.2%, 1 year 84.3%, 5 years 68.4%, 10 years 54.1% • Outcomes slightly better for living donor recipients

REFERENCES

1. Steadman RH. Anesthesia for liver transplant surgery. Anesthesiol Clin N Am. 2004;22:687–711. 2. Ozier Y, Klinck JR. Anesthetic management of hepatic transplantation. Curr Opin Anesthesiol. 2008;21:391–400.

3. Fabbroni D, Bellamy M. Anaesthesia for hepatic transplantation. Contin Educ Anaesth Crit Care Pain. 2006;6(5):171–175. 4. Ramsay MAE. Anesthesia considerations in liver transplantation. Recent developments in transplantation medicine: Liver transplantation. Available at: http://www.centerspan.org/pubs/liver/ramsay1.htm 5. OPTN Annual Report. Available at: http://optn.transplant.hrsa.gov/data/annualReport.asp 6. Starzl TE, Marchioro TL, Vonkaulla KN, et al. Homotransplantation of the liver in humans. Surg Gynecol Obstet. 1963;117:659–676. 7. Fonouni H, Mehrabi A, Soleimani M, et al. The need for venovnous bypass in liver transplantation. HPB. 2008;10:196–203.

ADDITIONAL READING

• Carithers RL. Liver transplantation. Liver Transplant. 2000;6(1):122–135. • Csete M, et al. Anesthesia for organ transplantation. In Barash PG, et al., ed. Clinical anesthesia. Philadelphia: Lippincott Williams and Wilkins, 2006:1364–1367.

See Also (Topic, Algorithm, Electronic Media Element) • Liver vasculature • End-stage liver disease

CODES ICD9 V42.7 Liver replaced by transplant ICD10 Z94.4 Liver transplant status

CLINICAL PEARLS

• Liver transplantation surgery is associated with large fluid shifts, potentially massive blood loss, and dramatic hemodynamic derangements that require adequate preparation and vigilant monitoring. • There may be some degree of institutional variability in surgical technique and monitoring resources that require careful consideration in preparing for and managing liver transplant procedures. Pediatric Considerations

• Grafts are often reduced from the adult liver (commonly left lateral segment or left lobe), and the raw surface of the graft is at risk of bleeding. Vascular access may be more challenging, and veno-venous bypass is not an option for children under 35–40 kg because of inadequate flow through small cannulae. Children have an increased risk of hepatic artery thrombosis (HAT) due to the small caliber of vessels and fluid overload. Transfusions must be carefully managed to avoid overtransfusion and overcorrection of coagulopathy due to risk of HAT.

LIVER VASCULATURE Michelle Braunfeld, MD

BASICS DESCRIPTION

• The liver is the largest endocrine organ. – It comprises approximately 2% of total body weight. – It is located in the right upper quadrant of the abdominal cavity, directly under the diaphragm. – The gallbladder sits in the fossa against the inferior surface, to the right of the falciform ligament. • Blood supply – The portal vein drains venous blood from the stomach, spleen, pancreas, and intestines. It provides approximately 70% of the hepatic blood supply. – The hepatic artery delivers arterial (oxygenated) blood; it provides approximately 30% of the hepatic blood supply. – The hepatic veins drain the liver and empty into the inferior vena cava. PHYSIOLOGY PRINCIPLES

• The liver receives a blood flow of approximately 1.5 Liters/minute and is responsible for 25% of the body’s metabolic activity. • The dual blood supply from the portal vein and hepatic artery maintains oxygen supply by reciprocal changes in flow in these vessels. Typically, the portal vein supplies 70–75% of the blood supply, while the hepatic artery supplies 25–30% of the blood supply. However, the oxygen supply from each of these sources is roughly 50%. • The liver coordinates processing and distribution of nutrients from the portal circulation. – Responsible for carbohydrate, protein, and vitamin metabolism – Urea cycle eliminates waste nitrogen. – Produces and secretes bile – Synthesizes all procoagulants except Factor VIII and von Willebrand factor – Clears activated coagulation factors and tPA – Metabolizes and eliminates toxins • Intrinsic regulation of blood flow: – Autoregulation: Describes the body’s ability to maintain a constant blood flow over a range of mean pressures. It is believed that the stretch from an increase in hepatic arterial perfusion pressure results in a myogenic contraction. Studies have shown that in a fasting liver, autoregulation is decreased (e.g., perioperatively). The portal circulation does not appear to demonstrate autoregulation and flow is pressure-dependent. – Metabolic control: Hepatic arterial blood flow increases during hypoxemia, hypercarbia, acidosis, and decreased portal oxygen tension. Increased osmolarity (e.g., digestion) also results in increased hepatic artery and portal venous blood flow.

– Hepatic arterial buffer response (HABR) describes the ability of the body to protect the liver during low-flow states by increasing hepatic arterial flow when portal venous blood flow is decreased. This results in a reciprocal relationship in order to maintain a stable oxygen supply. It is hypothesized that the build-up of adenosine in low-flow states is responsible for the vasodilation of the hepatic artery. • Extrinsic regulation of blood flow: – Neural control is via branches of the vagus and splanchnic nerves that enter the liver with blood vessels and bile ducts. There is an intercommunicating plexus that forms from the sympathetic and parasympathetic nerves and terminates on arterioles and venules. Sympathetic stimulation can divert 80% or approximately 500 mL of hepatic blood quickly, in response to hypercarbia, pain, or hypoxia; functions as a reservoir. – Humoral factors Epinephrine: The hepatic artery has both alpha- and beta-adrenergic receptors, and the portal venous system possesses alpha-receptors. Glucagon: A vasodilator of intestinal origin that causes splanchnic vasodilation, with resultant increase in portal blood flow Angiotensin II: Capable of profound vasoconstriction of the hepatic and portal systems, with concurrent reduction in mesenteric outflow; this results in a substantial reduction in total liver blood flow. Vasopressin: Splanchnic vasoconstrictor that decreases venous inflow of blood to the portal vasculature.

ANATOMY

• Functional anatomy divides the liver into 8 segments (Couinaud classification). Each segment is supplied by its own branch of the portal vein, hepatic artery, and bile duct (portal triad). • Hepatic artery originates from the celiac axis. Studies have shown that there are anomalous variations of the right or left hepatic artery in nearly 50% of dissections; additionally, when present, they are often multiple. • Portal vein is formed by confluence of the splenic vein and superior mesenteric vein.

DISEASE/PATHOPHYSIOLOGY

• Portal hypertension can result from cirrhosis. Blood outflow from the portal bed is impaired, resulting in increased pressure with the formation of collateral circulation to other areas of the general circulation (spleen, arteries, stomach). Esophageal varices develop at a hepatic venous pressure gradient (HVPG) of at least 10 mm Hg; variceal bleeding usually begins at 12 mm Hg. For prevention of variceal bleeding, portal hypertension is treated with nonselective beta-blockade (usually propranolol) to a target resting HR in the 50s or 25% below baseline. If beta-blockers are not tolerated, a long-acting nitrate may be used. • Ascites: 85% is associated with cirrhosis, and 15% is non-hepatic, e.g., associated with cardiac, renal, neoplastic, and tuberculous disease. Ascites associated with portal hypertension is caused by consequent splanchnic vasodilation and increased splanchnic lymph production. • Thrombosis of the liver vasculature: – Acute thrombosis is associated with pain, fever, and rapid development of ascites; varices

are not seen. Risk factors include intra-abdominal inflammatory processes, primary prothrombotic disorders, malignancy, and splenectomy. Acute thrombosis following liver transplantation is a devastating complication, requiring revascularization. – Portal venous thrombosis is most often associated with underlying cirrhosis, especially with concomitant malignancy. – Hepatovenous thrombosis (Budd–Chiari) is often associated with underlying malignancy and may cause massive blood loss during surgery. • Ischemic injury: Can result from prolonged hypotension, cardiogenic or noncardiogenic shock, hypoxemia, or surgical injury (hepatic artery ligation, post-transplant) • Hepatic congestion can result from right or left congestive heart failure and may result in hepatic fibrosis and cirrhosis.

PERIOPERATIVE RELEVANCE

• The extent of hepatic resection is described by segmental anatomy. For example: – Left lateral segmentectomy = segments 2, 3 – Left hepatic lobectomy = segments 2–4 – Extended left hepatic lobectomy or left trisegmentectomy = segments 2–5 – Right hepatic lobectomy = segments 5–8 – Extended right hepatic lobectomy or right trisegmentectomy = segments 4–8 • Cross-clamping to control surgical bleeding: – May involve selective clamping of inflow (portal triad) and/or outflow (hepatic veins) – The Pringle’s maneuver describes cross-clamping of the porta hepatis to decrease surgical bleeding; it is usually without significant hemodynamic consequence. – An extreme measure to control surgical bleeding in hepatic resection, termed “total hepatic vascular exclusion,” involves cross-clamp of the porta hepatis, infra-hepatic, and supra-hepatic cava. This can reduce venous return by 60–70%. • Transjugular intrahepatic portosystemic shunt (TIPS) is a percutaneous procedure that involves the creation of a portal vein to the hepatic vein tract, under fluoroscopic guidance. Primary indications include secondary prevention of variceal bleeding and refractory ascites. It may also be potentially beneficial in refractory varices, acutely bleeding varices, refractory hepatic hydrothorax, hepatorenal syndrome, failed anticoagulation in moderate Budd–Chiari syndrome, and re-bleeding after medical management in portal hypertensive gastropathy. • Octreotide and early endoscopic variceal sclerotherapy can be performed for the treatment of acute variceal bleeding. Shunt placement (either TIPS or surgical shunt) may be warranted for recurrent bleeding despite pharmacologic and endoscopic therapy. • Cholecystectomy requires isolation and detachment of the cystic artery.

REFERENCES

1. Abdel-Misih SRZ, Bloomston M. Liver anatomy. Surg Clin N Am. 2010;90:643–653. 2. Celinski SA, Gamblin TC. Hepatic resection nomenclature and techniques. Surg Clin N Am. 2010;90:737–748. 3. Garcia-Tsao G, Bosch J. Management of varices and variceal hemorrhage in cirrhosis. N Engl J Med. 2010;362(9):823–832.

See Also (Topic, Algorithm, Electronic Media Element) • Gastrointestinal blood flow • Cirrhosis • Transjugular intrahepatic portosystemic shunt (TIPS) • Cell salvage

CLINICAL PEARLS

• Regardless of the procedure planned, extent of underlying hepatic disease guides anesthetic management. • The liver is a highly vascular organ. Any procedure on it has the potential for massive blood loss. Assure adequate venous access. • If the patient has Budd–Chiari syndrome, there is no such thing as too much venous access. These patients have a high risk for massive, exsanguinating hemorrhage. • If massive transfusion is anticipated (variously defined as acute replacement of >10 U blood, >1 blood volume, or >1/2 blood volume per hour) discuss anticipated needs with the Blood Bank, plan for a “keep ahead” supply of blood products and discuss potassium minimization measures for RBCs.

LOCAL ANESTHETIC SYSTEMIC TOXICITY Angela T. Hsu, MD

BASICS DESCRIPTION

• Local anesthetic (LA) toxicity can range from mild symptoms to severe central nervous system (CNS) and cardiovascular (CV) toxicity that can result in death. • The severity of LA systemic toxicity is based on a variety of factors: – Regional block technique – Location – Type of local anesthetic utilized – Total dosage – Timeliness of detection and appropriate treatment – Individual patient risk factors • In addition to LA toxicity, local anesthetics, can also result in other adverse reactions: – Allergic reaction – Methemoglobinemia – Neurotoxicity (cauda equina syndrome, transient neurologic symptoms) EPIDEMIOLOGY Incidence

• Epidural injection: 1.2–11 per 10,000 blocks • Caudal injection: 1.3–69 per 10,000 blocks • Peripheral nerve blocks: 7.5–20 per 10,000 blocks

Morbidity

Severe cardiovascular and neurologic compromise Mortality

According to the ASA Closed Claims review of peripheral nerve blocks from 1980 to 2000, 7 of 19 claims associated with death or brain damage were attributed to LA systemic toxicity. ETIOLOGY/RISK FACTORS

• Risk factors for LA toxicity: – Location of regional block: Areas with high vascularity favor uptake of local anesthetic and result in higher blood levels. Intercostal > Caudal > Epidural > Brachial plexus > Sciatic > Spinal. – Type of local anesthetic: More potent, longer-acting LAs tend to be more toxic. The S(–) isomers (levobupivacaine and ropivacaine) seem to be less toxic than R(+) isomers or racemic bupivacaine.

– Technique and dosage Dose = volume × concentration Unnecessarily high dosing can increase the risk of serious toxicity if intravascular uptake occurs. Studies on ultrasound-guided regional blockade have indicated that with proper placement, smaller doses can provide adequate blockade. • Individual patient risk factors: – Patients at extremes of age (<4 months or >70 years) – History of cardiac conduction defects or ischemic heart disease – Cardiac, renal, and hepatic dysfunction are important predictors of local anesthetic plasma levels after a specific dose rather than body weight or BMI.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The mechanism of LA toxicity is highly controversial. Due to ethical concerns, no human randomized controlled trials exist. Data on this topic relies on animal studies and case reports. • In general, the CNS is more sensitive to LA toxicity than the CV system. For most local anesthetics, CV toxicity does not occur until 3 times the concentration necessary to produce seizures. This CV/CNS ratio tends to be lower with bupivacaine. • Hypoxia and hypercarbia can decrease the convulsive threshold and predispose to myocardial toxicity. • CNS toxicity: 2-phase pathophysiologic process: – First, preferential blockade of the inhibitory CNS pathways leaves the excitatory pathways unopposed. This can manifest as shivering/muscle tremors and proceed to tonic–clonic seizures. – With increasing plasma levels, both inhibitory and excitatory pathways are blocked. Generalized CNS depression ensues with potential respiratory arrest. • CV toxicity: One of the primary mechanisms of CV toxicity is thought to be from binding and inhibition of Na+ channels by LAs. At higher concentrations, it is believed that cardiac Ca2+ and K+ channels are also inhibited. LAs are also thought to antagonize betaadrenergic receptors. 2-phase pathophysiologic process: – In the CNS excitatory phase, activation of the sympathetic nervous system results in tachycardia and hypertension. – With increasing plasma levels, bradycardia, hypotension, and ventricular arrhythmias occur.

PREVENTATIVE MEASURES

According to the 2010 American Society of Regional Anesthesia (ASRA) practice advisory: • Use lowest effective dose of LA • Incremental dosing: Pause 15–30 seconds between each 3–5 mL dosing. • Aspirate for blood prior to each injection. • Consider using a pharmacologic marker/test dose to identify inadvertent intravascular injection: – Epinephrine 15 μg produces a greater than 10 beat increase in heart rate or a greater than

15 mm Hg increase in systolic blood pressure. – Note that beta-blockers, advanced age, labor, and general/neuraxial anesthesia may inhibit this response. – Fentanyl 100 μg produces sedation in laboring patients. • Ultrasound guidance: Reportedly decreases the incidence of intravascular injection. Whether it decreases actual incidence of LA systemic toxicity still remains to be answered.

DIAGNOSIS • Classically in LA systemic toxicity, CNS symptoms are followed by CV symptoms. However, in review of case reports, there is extreme variability in presentation. • Particularly with potent local anesthetics, cardiac toxicity may occur simultaneously or precede seizures. Sometimes CV toxicity is the only manifestation. • CNS toxicity: – Classic early symptoms: Circumoral numbness, metallic taste, lightheadedness, visual/auditory disturbances, agitation/tremors – Later symptoms: Seizure, coma, respiratory arrest • CV toxicity: – First, cardiac excitation: Tachycardia, hypertension, ventricular arrhythmias – Later, CV depression: Bradycardia, hypotension, decreased contractility, asystole

DIFFERENTIAL DIAGNOSIS

Pain during uterine contraction may also produce increased heart rate.

TREATMENT • Airway management is of utmost importance. Prevention of hypoxia and hypercarbia/acidosis can halt progression of LA toxicity to seizures and/or CV collapse, as well as aid in successful resuscitation. • For seizures, the first-line therapy is benzodiazepines. Small doses of thiopental or propofol may also be used, realizing this may worsen hypotension/CV depression. Avoid propofol when there are signs of CV compromise. Future studies may support lipid infusion as the initial treatment. • If seizures persist, consider small doses of neuromuscular blockers to halt muscle contractures, thus preventing further oxygen consumption and CO2 production. Seizures

(electrical function) may continue despite a lack of tonic–clonic muscle activity. • For cardiac arrest, perform standard ACLS with the following modifications: – Small doses of epinephrine (<1 μg/kg) if needed – Avoid vasopressin – Avoid calcium channel blockers and beta-blockers – For ventricular arrhythmias, amiodarone is preferred. Avoid local anesthetics (i.e., lidocaine, procainamide). • 20% Lipid emulsion therapy – Consider starting the infusion immediately after airway management. Lipid emulsion can

be a significant aid in resuscitation, acting as a “lipid sink,” drawing lipophilic local anesthetic from within cardiac tissues. – Dosing Bolus 1.5 mL/kg over 1 minute Infusion of 0.25 mL/kg/min for at least 10 minutes after circulatory stability is achieved. If the patient is still unstable, re-bolus and increase the infusion to 0.5 mL/kg/min. Recommended upper limit: 10 mL/kg over 30 minutes – Note: Propofol is not a substitute for lipid emulsion. • Consider cardiopulmonary bypass (CPB) if inadequate responses to lipid emulsion and vasopressor therapy.

FOLLOW-UP • Delayed re-occurrence of LA systemic toxicity has been reported. – Continue close monitoring of patients for 12 hours after severe episodes. – Maintain oxygenation and ventilation. – Once the patient is stabilized from the initial episode of LA systemic toxicity, consider consultation with a cardiologist or intensivist. – Recommend stay in a monitored setting/ICU setting to observe for signs of recurrent cardiac or central nervous system toxicity. • There are concerns of possible adverse effects following lipid therapy. – Lipid emulsion for TPN is associated with pancreatitis; however, there have been no reported cases associated with lipid infusion for LA toxicity. – Further observation and studies are needed to fully elucidate the possible adverse effects of lipid therapy for LA toxicity.

CLOSED CLAIMS DATA

LA systemic toxicity accounts for 1/3rd of claims for death or brain damage associated with regional anesthesia.

REFERENCES

1. Butterworth JF. Local anesthetics: Mechanisms, toxicities, and controversies from a clinical perspective. American Society of Anesthesiologists Annual Meeting, San Diego, CA, 2010. 2. Drasner K. Local anesthetic systemic toxicity: A historical perspective. Reg Anesth Pain Med. 2010;35:160–164. 3. Groban L. Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Reg Anesth Pain Med. 2003;28(1):3–11. 4. Lee LA, Posner KL, Cheney FW, et al. Complications associated with eye blocks and peripheral nerve blocks: An American Society of Anesthesiologists Closed Claims Analysis. Reg Anesth Pain Med. 2008;33(5):416–422. 5. Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: Incidence and preventive measures. Reg Anesth Pain Med. 2002;27(6):556–561. 6. Neal JM, Bernards CM, Butterworth JF 4th, et al. ASRA practice advisory on local

anesthetic systemic toxicity. Reg Anesth Pain Med. 2010;35(2):152–161. 7. Weinberg GL, Ripper R, Murphy P, et al. Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart. Reg Anesth Pain Med. 2006;31:296–303. See Also (Topic, Algorithm, Electronic Media Element) • Methemoglobinemia • Transient neurologic symptoms • Epidural • Caudal epidural • Cardiopulmonary bypass

CODES ICD9 968.9 Poisoning by other and unspecified local anesthetics ICD10 T41.3X1A Poisoning by local anesthetics, accidental, init

CLINICAL PEARLS

• Be prepared to handle severe LA systemic toxicity by preparing a LA toxicity kit, including lipid emulsion therapy and posting instructions on its use. • When performing a regional or neuraxial anesthetic technique, use the smallest dose of local anesthetic necessary. • Use a pharmacologic marker/test dose to aid with identification of vascular injection. • Inject 3–5 mL aliquots followed by aspiration to assess for blood. Pause for 15–30 seconds prior to resuming injection to ask the patient if they are experiencing symptoms of toxicity and observe for signs. • Be vigilant. Monitor patient during and after the injection, noting that toxicity can present >30 minutes after injection. • Consider LA toxicity in any patient with altered mental status, neurologic symptoms, or CV instability following a regional anesthetic. • Note that >40% of cases do not follow the classic presentation of local anesthetic systemic toxicity. Cardiovascular signs may be the only manifestation in severe cases.

LOWER EXTREMITY AMPUTATION Menelaos Karanikolas, MD, MPH

BASICS DESCRIPTION General

• Lower extremity (LE) amputation is one of the oldest known surgical procedures. It can be classified as: – Minor: Removal of a toe or part of the foot – Major: Removal of part of the leg. It is further described as a below-the-knee amputation (BKA) or an above-the-knee amputation (AKA). • Indications for LE amputation include: End-stage peripheral vascular disease (PVD), trauma, tumor, infection, congenital limb deficiency, and painful, non-functional limbs. In recent years, as prosthesis technology has advanced, the indications for elective amputation have expanded. • Surgical technique is important for long-term functional outcome. Use of a pneumatic tourniquet reduces blood loss and the need for transfusion (1)[B]. After incision, the muscle compartments are isolated, and the main arteries, veins, and nerves are identified. Arteries and veins are ligated separately, in order to avoid arteriovenous fistula formation. Nerves are transected under tension as proximally as possible, and are then allowed to retract in the soft tissues, in an attempt to avoid neuroma formation. • The bone is cut and the bony edges are smoothed, to minimize postoperative soft-tissue trauma and pain with application of a prosthesis. Several techniques (myoplasty or myodesis) can be used to place muscle over the cut end of the bone. Enough skin should be preserved to cover the muscle and achieve a symmetric, smooth, tension-free closure. At the end of surgery, drains are placed to avoid formation of wound hematoma. • A guillotine (or open) amputation is a quicker procedure, and is reserved for cases with infection, contaminated trauma, or uncertain survival; it leave an open wound at the end of the stump. Blood vessels are ligated and nerves are cut as described above, but the wound is not closed. Instead, the stump is dressed with gauze and application of bandages. Later, when the risk of infection is reduced, the amputation can be revised higher or grafted. • Postoperative pain, depression, need for rehabilitation, and appropriate application of prosthesis are important long-term considerations. Position

Supine: A bump under the hip is often used to limit limb rotation. Incision

Anterior and posterior, above the line of ischemic tissue demarcation Approximate Time

1–2 hours

EBL Expected

• BKA: 200 mL • AKA: >250 mL

Hospital Stay Up to 7 days

Special Equipment for Surgery

• Saw or guillotine • Pneumatic tourniquet • Vascular and orthopedic instruments

EPIDEMIOLOGY Incidence

In the US: 30,000–40,000 procedures per year (2)[B] Prevalence

In the US in 2005, 1.6 million people lived with loss of a limb; this number is projected to double by 2050 (2)[B].

Morbidity

Cardiac, respiratory (most patients are smokers), infection (most patients have diabetes), nonhealing wound, re-amputation, acute pain, phantom limb pain (PLP), and stump pain Mortality

Very high given the comorbidities of the patient population. Median survival is 20–27 months after AKA and 52 months after BKA (3)[B]. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintain hemodynamic stability: These patients are at high risk for coronary artery disease; thus, hypotension and tachycardia should be avoided. Tourniquet pain can cause tachycardia and hypertension, which can be treated with beta-blockers, opioids, or increasing the anesthetic depth. Depending on preoperative hemoglobin and surgical blood loss, transfusion of RBCs may be needed. • Use of an epidural or regional block has the advantage of avoiding general anesthesia and mechanical ventilation, and may decrease intraoperative and immediate postoperative pain. It is not clear, however, if it decreases the incidence of PLP (4)[B].

PREOPERATIVE ASSESSMENT SYMPTOMS

• Severe ischemic and/or neuropathic LE pain • Symptoms of coronary artery disease or ischemic cardiomyopathy

History

Inquire about diabetes, smoking, hypertension, chronic obstructive pulmonary disease, symptoms of coronary artery disease or congestive heart failure. Confirm the timing of hemodialysis in patients with renal failure. Signs/Physical Exam

No special considerations MEDICATIONS

• Beta-blockers should be continued perioperatively. • Antiplatelet agents: Generally should be discontinued for 7–14 days before surgery. However, the risk of discontinuation (e.g., thrombosis to coronary or cerebral vasculature) should be discussed with the surgeon and primary care physician. Additionally, it is not always feasible when the amputation is urgent. • Oral antihyperglycemics should be held on the morning of surgery to avoid hypoglycemia while the patient is NPO. Blood glucose can be checked perioperatively, and insulin can be administered to treat hyperglycemia. • Antihypertensive medications should generally be continued throughout the perioperative period. ACE inhibitors, however, have been associated with severe hypotension and should perhaps be discontinued 24–48 hours before surgery. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• EKG (coronary artery disease) • Hemoglobin: Values >10 g/dL are recommended to ensure adequate oxygen delivery for wound healing. • Blood glucose in diabetic patients: Hyperglycemia is associated with increased risk of infection. • Serum albumin: Values <3.5 g/dL indicate malnutrition and increased risk of impaired wound healing. CONCOMITANT ORGAN DYSFUNCTION

• Respiratory (COPD related to smoking) • Cardiovascular • Renal, central and peripheral nervous system (history of stroke, diabetic neuropathy)

TREATMENT PREOPERATIVE PREPARATION Premedications

• Beta-blockers, insulin as appropriate • Transfusion of FFP may be needed to correct coagulopathy (prolonged PT, INR). pRBCs should be considered for anemia, in an attempt to increase oxygen tissue delivery and

improve wound healing.

Special Concerns for Informed Consent

BKA is an intermediate cardiac risk procedure, whereas AKA is a high cardiac risk procedure. Reported perioperative mortality is 0.9–14% for BKA versus 2.8–35% for AKA, and median survival is 52 months after BKA versus 20–27 months after AKA (3)[B].

Antibiotics/Common Organisms

• Cefazolin 1–2 g IV for skin organisms • May need additional antibiotics in cases of infection, contamination, or gangrene

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia if the patient is on anticoagulants or antiplatelet medications • Regional with/without general anesthesia – Neuraxial (spinal or epidural) is an excellent choice (if no contraindications). Potential benefits include improved perioperative analgesia, increased limb perfusion due to sympatholysis, reduced blood loss, and reduced risk of deep venous thrombosis. – Regional blocks (femoral and sciatic) could be considered in anticoagulated patients.

Monitors

Arterial line may be considered for tight blood pressure control, as well as glucose, and hemoglobin monitoring. Induction/Airway Management

Endotracheal intubation for general anesthesia should be considered in patients at risk for aspiration, such as diabetes, pain, or trauma. Consider a rapid-sequence induction. Maintenance

• Use of a pneumatic tourniquet during amputation significantly reduces blood loss and transfusion requirements (1)[B], but can have significant hemodynamic effects. • Tourniquet “up” – Afterload: Systemic vascular resistance (SVR) is increased mechanically (from vascular occlusion) and secondary to norepinephrine release in response to tourniquet pain. – Preload: Increases due to “exsanguination” of the limb before the tourniquet is inflated – Cardiac output (CO): Unchanged initially, but gradually increases above baseline. • Tourniquet “down” – Afterload: The mechanical afterload decreases, and acid metabolites (such as lactate) that are released into the circulation on reperfusion cause vasodilation. – Preload: Decreases, as blood is allowed to return to the remaining limb – Cardiac output: Generally increases after amputation, but blood pressure decreases due to reduced preload and afterload. Overall, hypotension is less pronounced compared to nonamputation procedures because the load of return of metabolites entering the circulation is reduced after removal of the ischemic limb.

Extubation/Emergence

No special considerations

POSTOPERATIVE CARE BED ACUITY

• Recovery room and then regular floor • ICU care may be considered if the patient was critically ill before surgery.

ANALGESIA

Acute postoperative and chronic PLP and stump pain are significant issues. The pathophysiology of PLP is not fully understood, but cortical reorganization plays a major role. Severe preamputation pain is associated with PLP development. Several analgesic interventions, including preemptive analgesia, continuous nerve blocks, continuous epidural analgesia, epidural or IV ketamine, and oral gabapentin have been evaluated for PLP prevention, with inconclusive results. However, recent data suggest that optimized perioperative analgesia reduces PLP incidence and intensity, regardless of the analgesic modality used (4)[B]. Established phantom pain can be very difficult to treat.

COMPLICATIONS

• Cardiovascular (myocardial infarction, arrhythmias, congestive heart failure, stroke) • Respiratory (pneumonia, respiratory failure) • Ulcers, gangrene, non-healing wound • Osteomyelitis • Chronic pain, depression, and disability

PROGNOSIS

• Amputation for PVD: 15–30% of patients need contralateral amputation within 3 years. • Amputation for trauma: Severe long-term disability regardless of amputation level (5)[B] • Amputation for pediatric bone tumors: Survivors have significant long-term deficits in education and employment (6)[B]. • The level of LE amputation is important because energy expenditure for walking increases, and walking speed decreases with higher levels of amputation. In recent years there is a trend for fewer AKAs and more BKAs.

REFERENCES

1. Choksy SA, Lee Chong P, Smith C, et al. A randomised controlled trial of the use of a tourniquet to reduce blood loss during transtibial amputation for peripheral arterial disease. Eur J Vasc Endovasc Surg. 2006;31:646–650. 2. Ziegler-Graham K, MacKenzie EJ, Ephraim PL, et al. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008;89:422–429. 3. Subramaniam B, Pomposelli F, Talmor D, et al. Perioperative and long-term morbidity and mortality after above-knee and below-knee amputations in diabetics and nondiabetics. Anesth Analg. 2005;100:1241–1247. 4. Karanikolas M, Aretha D, Tsolakis I, et al. Optimized perioperative analgesia reduces

chronic phantom limb pain intensity, prevalence, and frequency: A prospective, randomized clinical trial. Anesthesiology. 2011;114:1144–1155. 5. MacKenzie EJ, Bosse MJ, Castillo RC, et al. Functional outcomes following trauma-related lower-extremity amputation. J Bone Joint Surg Am. 2004;86-A(8):1636–1645.

6. Nagarajan R, Neglia JP, Clohisy DR, et al. Education, employment, insurance, and marital status among 694 survivors of pediatric lower extremity bone tumors. Cancer. 2003;97:2254–2264.

ADDITIONAL READING

• Jaffe RA, Samuels SI. Anesthesiologist’s manual of surgical procedures, 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2009:1047–1051. See Also (Topic, Algorithm, Electronic Media Element)

• Peripheral vascular disease • Diabetes mellitus • Epidural

CODES ICD9 897.4 Traumatic amputation of leg(s) (complete) (partial), unilateral, level not specified, without mention of complication ICD10 • S88.919A Complete traumatic amp of unsp lower leg, level unsp, init • S88.929A Partial traumatic amp of unsp lower leg, level unsp, init

CLINICAL PEARLS

• Above-the-knee (AKA) or below-the-knee amputation (BKA) is a major procedure with a high perioperative morbidity and mortality. • Patients scheduled for AKA and BKA typically have numerous comorbidities including diabetes, coronary artery disease, chronic obstructive pulmonary disease, renal insufficiency, and peripheral neuropathy. • Optimized perioperative analgesia may reduce phantom pain.

LOWER EXTREMITY BYPASS Kenneth F. Kuchta, MD

BASICS DESCRIPTION General

• Most patients with peripheral vascular disease are managed medically. Endovascular procedures with balloon angioplasty and stenting are less invasive procedures but are also less durable and have technical limitations when the blockage is extensive. • The goal of lower extremity bypass is to improve blood flow, reduce pain, improve functional ability and quality of life, and prevent amputation. Common causes include: – Arterial occlusive disease due to atherosclerosis; most common – Thromboembolic, inflammatory, or traumatic events. Femoral and popliteal artery aneurysms and pseudoaneurysms are often repaired to prevent thromboembolic events as well as rare ruptures. – Advential cysts, entrapment. – As part of tumor resections • The procedure entails creating an alternate conduit for blood flow to circumvent the area of blockage and restore direct flow to the lower leg and foot. The conduit can include harvested veins (saphenous or other vein from the arm or leg) or an artificial, prosthetic graft. • Acute occlusion is a surgical emergency and is treated with embolectomy, thrombolysis, or bypass. Position

• Usually supine • Occasionally other positions may be required, such as prone for some popliteal aneurysms.

Incision

• Sufficient to expose the proximal and distal anastomosis • Additional incisions (often long) for the vein harvest may be needed, though this may be minimized with in situ grafts or endovascular harvests. Approximate Time

Highly variable (1 hour to all day) depending on the extent of bypass and the anatomic intricacies of the procedure EBL Expected

• Usually minimal blood loss • Revision procedures, infected grafts, or intraoperative difficulties can increase blood loss.

Hospital Stay

3–5 days in uncomplicated cases Special Equipment for Surgery

In patients lacking suitable autologous veins (prior harvest or excision), synthetic graft (e.g., PTFE) or cryopreserved vessels may be needed. In an infected field, cryovessel is preferred over PTFE. EPIDEMIOLOGY Incidence

Peripheral arterial disease (PAD) incidence increases with age. Prevalence

• PAD estimates vary widely; American Heart Association (AHA) states about 8 million Americans. • PAD affects approximately 20% of adults over the age of 55 years.

Morbidity

• Per National Surgical Quality Improvement Program (NSQIP), in 2004, major 30-day morbidity was 18.7%. – Wound complications (∼75% of all complications): Dehiscence, wound and organ space infection, sepsis, bleeding, and graft failure – Systemic complications: Failure to wean, reintubation, pneumonia, renal failure, pulmonary embolism, stroke, coma, cardiac arrest, and deep venous thrombosis • Morbidity was also higher in those undergoing surgery for limb ischemia: 30.1% (1).

Mortality

• Operative mortality of approximately 1–3% • Per NSQIP data, mortality was 2.7% in 2004; patients with critical limb ischemia had an increased mortality of 3.6% (1). ANESTHETIC GOALS/GUIDING PRINCIPLES

• Although the surgery itself does not typically pose significant challenges for the anesthetist, the comorbidities present significant risks and warrant careful evaluation and perioperative management. • The AHA guidelines rank infrainguinal bypass procedures as a high-risk procedure (on par with open aortic procedures, and greater than intermediate-risk procedures such as carotid endarterectomies and endovascular aortic repairs). – Claudication makes clinical assessment more difficult (unable to assess exercise tolerance, perform treadmill stress testing). – Shared risk factors for coronary disease and peripheral vascular disease may also be more prevalent in patients undergoing lower extremity bypasses. Hence having infrainguinal vascular disease may be a “marker” for sicker patients.

PREOPERATIVE ASSESSMENT

SYMPTOMS

• Early–mild intermittent claudication: Pain or fatigue in the leg muscles with exercise and relieved by rest • Late–severe disabling claudication or rest pain: Pain may be worse when lying flat and improved when the feet are dependent. • Toe and foot sores that do not heal • Acute occlusion is characterized by a sudden onset of the 5 “P”s: Pain, pallor, pulselessness, paresthesias, and paralysis. • Cardiovascular status – Past cardiac disease and evaluations as well as symptoms of chest pain and dyspnea – Evaluation of exercise tolerance should recognize that patients frequently have asymptomatic cardiac disease due to claudication. They will frequently say their walking is limited by leg pain and not chest pain. Exercise tolerance is thus often inconclusive as a screen for cardiac reserve in these patients.

History

Focus on evidence of atherosclerotic vascular disease in the heart, brain, and kidneys. Symptoms of cardiac disease may be masked since claudication may limit exertion. Signs/Physical Exam

• Lower extremity pallor, cyanosis, dependent rubor, coolness, atrophy, and decreased hair or nail growth may be noted with diminished or absent distal pulses in the evaluation by the surgical consult. – Evaluation by ankle brachial index (the ratio of the ankle to the arm pressure): A ratio <0.9 or >1.3 is abnormal, and ≤0.4 indicates severe peripheral vascular disease. – Further evaluation often leads to angiography along with attempts at angioplasty, stenting, or other minimally invasive vascular procedures. • Cardiac exam for evidence of heart failure • Carotid bruits can be significant, though often a carotid duplex has already been performed. • Pulmonary exam may indicate the adverse effects of smoking.

MEDICATIONS

• Due to concomitant disease • Beta-blocker (and potentially a statin) may have been added to reduce cardiac risk.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, BUN, creatinine, glucose • EKG • CXR • Cardiac stress testing, echocardiogram, and/or cardiac catheterization data may have been performed as part of a cardiac evaluation. CONCOMITANT ORGAN DYSFUNCTION

• Generalized vascular disease: Cardiac and cerebral • Effects of smoking • Diabetes • Hypertension • Dyslipidemia • Renal failure

TREATMENT PREOPERATIVE PREPARATION Premedications

• Perioperative beta-blockade may be started (2)[B]. – However, studies with the most favorable outcomes initiated beta-blockade at least a week before surgery (3)[B]. – A more recent study demonstrated reduced incidence of myocardial infarction, but increased risk of stroke and a higher death rate (4)[B]. The dose of beta-blocker, however, was criticized as being relatively high.

Special Concerns for Informed Consent

• Consent for possible blood transfusion, planned or possible invasive monitors • Review of the risk of cardiac and cerebral vascular complications

Antibiotics/Common Organisms

Routine prophylactic antibiotics for skin organisms unless already on a specific antibiotic for limb infection INTRAOPERATIVE CARE Choice of Anesthesia

• General, epidural, spinal, and even nerve blocks have been successfully utilized. • Epidurals have the possible advantage of avoiding airway instrumentation and the potential stress of general anesthesia as well as improved graft patency. Reductions in cardiac and pulmonary complications and graft thrombosis have been inconsistently seen in a variety of studies. • General anesthesia offers a secure airway, avoids the hemodynamic changes of a sympathectomy, and may be better tolerated (and preferred by patients) in longer procedures. • Peripheral nerve blocks may offer an alternative to neuraxial techniques when anticoagulants/antiplatelets therapy contraindicates neuraxial placement. Monitors

• Arterial line monitoring is useful for blood pressure monitoring and frequent blood draws. • A urinary catheter is frequently placed in expected lengthy procedures and to assist in monitoring volume status. • Consider central line monitoring per the patient’s underlying disease. Pulmonary artery

catheterization and/or transesophageal echocardiography may be indicated in more severe cardiac disease.

Induction/Airway Management

A slow, controlled induction may produce fewer or more tightly controlled hemodynamic swings. Maintenance

Hemodynamic stability is critical to preserve perfusion through the cerebral, myocardial, and renal vessels. Extubation/Emergence

• Extubation at the end of the case is usually feasible. • A hemodynamically smooth emergence and extubation may be beneficial in the setting of cardiac disease.

POSTOPERATIVE CARE BED ACUITY

ICU admission is dictated by the patient’s underlying disease and operative course, otherwise a regular bed is appropriate. ANALGESIA

Mild-to-moderate pain can be managed with opioids or, if present, epidural analgesia. COMPLICATIONS

• Cardiovascular and cerebral vascular events • Graft thrombosis; may be increased with prosthetic grafts • Infection (including progression of a pre-existing limb infection); although successful revascularization can facilitate improvement of an infection and closure of an ischemic wound.

PROGNOSIS

For those with claudication, the risk for future cardiovascular events is higher than the risk of limb ischemic events.

REFERENCES

1. LaMuraglia GM, Conrad MF, Chung MA, et al. Significant perioperative morbidity accompanies infrainguinal bypass surgery: An NSQIP report. J Vasc Surg. 2009;50:299– 304. 2. Mangano DT, Layug EL, Wallace A, et al. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med. 1996;335:1713–1720. 3. Poldermans D, Boersma E, Bax JJ, et al. The effect of bisoprolol on perioperative mortality

and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group. N Engl J Med. 1999;341:1789–1794. 4. Devereaux PJ, Yang H, Yusuf S, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): A randomised controlled trial. Lancet. 2008;371:1839–1847.

ADDITIONAL READING

• Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: Executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation. 2007;116:1971–1996. • Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): Executive summary. A collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease). Circulation. 2006;113(11):e463–e654. See Also (Topic, Algorithm, Electronic Media Element)

• Peripheral vascular disease • Cerebrovascular disease/TIA • Coronary artery disease

CLINICAL PEARLS

• As endovascular options have begun to replace many lower extremity bypasses (due to lower morbidity and mortality rates), the remaining operative procedures are often much more challenging and complex.

LUSITROPY

Teodora Orhideea Nicolescu, MD

BASICS DESCRIPTION

• Lusitropy describes the ability of the myocardium to relax following contraction, and hence the ventricle’s diastolic function. • Maintaining cardiac output is a direct function of normal contraction (inotropy) and relaxation (lusitropy) properties. PHYSIOLOGY PRINCIPLES

• Myocardial contraction: Electrical depolarization activates the voltage-gated sodium channels and triggers a rapid release of calcium from the sarcoplasmic reticulum. The initial burst of calcium release is inhibited by ryanodine (discontinues sarcoplasmic calcium release into the intracellular space). Calcium is a principal controlling mechanism of actin– myosin interaction. • Calcium binds to troponin C which then allosterically modulates tropomyosin; this results in uncovering of actin binding sites. When uncovered, myosin heads can bind and hydrolyze ATP (converts the chemical energy in ATP into mechanical energy; ATP → ADP + phosphate) to drive filament sliding; known as a cycle. Repeated cycles result in the movement of myosin heads along actin filaments, resulting in contraction.

FIGURE 1. Tropomyosin chains cover actin binding sites. When calcium binds to troponin C, tropomyosin uncovers or “exposes” the actin binding sites which allows myosin to bind.

• Myocardial relaxation, hence, results from the removal and sequestration of intracellular calcium. A decrease in calcium concentration results in decreased binding to troponin C and tropomyosin “re-covering” the actin binding sites, and myosin “unbinding.” Calcium removal is performed by the: – Sarcoplasmic reticulum calcium ATPase (SERCA): SERCA proteins are highly regulated by phospholamban and sarcolipin; they are also sensitive to thyroid hormone action. – Na+/Ca2+ ion exchanger

– Ca-ATPase (located in the sarcolemma) • Positive lusitropy describes increased relaxation. – Beta-agonists increase contractility/inotropy/chronotropy and are also important in improving relaxation via improved calcium ion uptake. This allows for subsequent normal filling and preload, and improved cardiac output. – At a molecular level, beta-agonism decreases the amount of calcium available for binding with troponin C by phosphorylating the phospholamban molecule. Normally, nonphosphorylated phospholamban is a SERCA antagonist, and decreases intracellular calcium removal.

FIGURE 2. Effects of left ventricular diastolic failur caused by decreased ventricular compliance (e.g., hypertrophy) on left ventricular pressure-volume loop. Heart rate, inotropy and systemic vascular resistance are unchanged.

• Negative lusitropy describes decreased relaxation and involves: – Increased intracellular calcium – Impaired SERCA function: Seen with aging (also combined with interstitial fibrosis and increased cross-linking of collagen that can cause stiffness). – Increased affinity of troponin C to calcium • Intracellular acidosis may inhibit calcium reuptake by the sarcoplasmic reticulum.

DISEASE/PATHOPHYSIOLOGY

• Diastolic dysfunction, or negative lusitropy, results in impaired ventricular compliance. – On a molecular level, it is related to an imbalance in the distribution of phospholamban and SERCA. The increased levels of intracellular calcium result in impaired lusitropy. – Increased left ventricular end-diastolic pressures (LVEDP) will decrease preload (LVEDV), with resultant decreases in stroke volume and cardiac output – Over time, left atrial and pulmonary arterial pressures can increase (this can result in

elevated right ventricular afterload) – Coronary perfusion pressure (CPP) also decreases secondary to increased intraventricular pressures during diastole (CPP = MAP – LVEDP, where MAP is mean arterial pressure).

PERIOPERATIVE RELEVANCE

• Diastolic dysfunction is an independent determinant of heart failure; poorer outcomes are seen when it is present early in post-acute myocardial dysfunction. It is diagnosed in 3 steps: – Clinical (heart failure) – Normal ejection fraction – Increased diastolic filling pressures • Echocardiographic indices: – Isovolumic relaxation time (normal 70 ms) is the time interval between aortic valve closure and mitral valve opening. When prolonged, it indicates poor myocardial relaxation. – Transmitral inflow (E/A ratio): The “E” wave represents flow during the rapid filling phase of ventricular diastole (after mitral valve opening); it represents the left atrial to left ventricular gradient. The “A” wave represents flow during atrial contraction and is approximately one-third to one-half the size of the E wave. During impaired relaxation, the E wave decreases in size (decreased left atrial-left ventricular gradient), the A wave increases in size (increased contribution), and the E/A ratio is <1. As impaired ventricular relaxation progresses, left atrial pressures increase in tandem and can cause pseudonormalization of the E/A ratio (>1). The normal appearing E wave reflects the increase in passive filling from the increased left atrial-left ventricular gradient. The normal appearing A wave reflects the decreased contribution of the atrial contraction. – Deceleration time: Describes the time it takes for the E wave velocity to become zero (normal is <220 milliseconds). In impaired relaxation, it exceeds 240 ms.

EQUATIONS

CPP = MAP – LVEDP, where CPP is coronary perfusion pressure, MAP is mean arterial pressure, and LVEDP is left ventricular end diastolic pressure.

REFERENCE

1. Chemla D, Lecarpentier Y, Martin JL, et al. Relationship between inotropy and relaxation in rat myocardium. Am J Physiol Heart Circ Physiol. 1986;250:H1008–H1016. [C] 2. Chen Y, Escoubert B, Prunier F, et al. Constitutive cardiac overexpression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase delays myocardial failure after myocardial infarction in rats at a cost of increased acute arrhythmias. Circulation. 2004;109:1898–1903. [A] 3. Coudray N, Beregi JP, Lercarpentier Y, et al. Effects of isoproterenol on myocardial relaxation rate: Influence of the level of load. Am J Physiol Heart Circ Physiol. 1993;265:H1645–H1653.

4. Fein FS, Kornstein LB, Strobeck JE, et al. Altered myocardial mechanics in diabetic rats. Circ Res. 1980;47:922–933. 5. Katz AM. Influence of altered inotropy and lusiotropy on ventricular pressure-volume loops. J Am Coll Cardiol. 1988;11:438–445. [B]

6. Satoh N, Sato T, Shimada M, et al. Lusiotropic effect of MCC-135 is associated with improvement of sarcoplasmic reticulum function in ventricular muscles of rats with diabetic cardiomyopathy. J Pharmacol Exp Ther. 2001;298:1161–1166. See Also (Topic, Algorithm, Electronic Media Element) • Chronotropy • cAMP • Cardiac action potential • Diastole

CLINICAL PEARLS

• Myocardial relaxation is influenced negatively by calcium overload. • Diastolic dysfunction can independently cause heart failure or can be associated with systolic heart failure. Emerging evidence has suggested that myocardial remodeling and diastolic dysfunction are far more important in heart failure pathogenesis than systolic dysfunction.

MAGNESIUM

Matthew C. Gertsch, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION • Magnesium (Mg2+) is a vital and abundant cation that plays a role in enzyme function, ATP synthesis, potassium balance, bone stability, and neurotransmission. Consequently, abnormalities can manifest as a variety of pathophysiologic scenarios. • Hypomagnesemia commonly presents in the perioperative period with non-specific signs and symptoms. Furthermore, it is associated with several pathologic processes (hypokalemia, arrhythmias, mitral valve prolapse, migraines, anxiety and psychiatric disorders, fibromyalgia, diabetes, hearing loss, osteoporosis, dysmenorrhea, asthma, and allergies). • Hypermagnesemia’s clinical presentation ranges from hyporeflexia to respiratory depression to cardiac arrest. It often results from exogenous replacement for the treatment of arrhythmias, hypokalemia, asthma, and preeclampsia, as well as hemolysis, or impaired renal function. PHYSIOLOGY PRINCIPLES

• Mg2+ is the fourth most common cation in the body and the second most common intracellular cation (following potassium) (1). • Distribution: Similar to potassium, magnesium is unevenly distributed throughout the body. It has been described as a physiologic calcium antagonist (regulates entry into the cell and intracellular action). Intracellularly, it is bound to ATP and enzyme complexes (1). – Bone (contains approximately 50% of total body stores). Functions to provide physical structure or scaffolding and regulates calcium and phosphorus. By binding to vitamins B6, D, and K, it regulates the absorption of calcium into bone. Thus, it is necessary for mineralization. Bone also serves as a “storage” site that can be drawn upon during times of low concentration. – Muscle (contains approximately 25% of total body stores). Plays a role in relaxation by blocking calcium influx. – Nerve cells – Nucleic acid synthesis – Energy metabolism – Red blood cells: Hemolysis may falsely elevate serum measurements. • Extracellular or serum (contains approximately 0.3% of total body stores). Present in ionized form, attached to anions, and bound to protein. Free Mg2+ is physiologically active. Similar to potassium, serum levels do not necessarily reflect total body stores. Furthermore, plasma levels are the major regulators of urinary Mg2+ excretion. • Absorption is via dietary oral intake and gastrointestinal absorption (primarily in the ileum

and colon). • Excretion: Renally cleared. • Regulation: primarily renal. Serum magnesium is filtered at the glomerular level into the renal tubule. Reabsorption occurs along the tubule to regulate serum levels. Its control is complex and at this time, no single hormone has been implicated in this process. It is known, however, that calcium and potassium levels affect reabsorption (2).

PATHOPHYSIOLOGY

• Hypomagnesemia (<1.4 mEq/L). Recently, the incidence of hypomagnesemia has increased, and may be attributed to changes in modern diets. Studies have shown that up to 11% of hospitalized patients and up to 65% of ICU patients may have Mg2+ deficiency. • Causes of hypomagnesemia. In addition to reduced intake, levels can also be reduced by gastrointestinal or renal loss. – Gastrointestinal losses can result from small bowel disorders including acute and chronic diarrhea, malabsorption, volume expansion (decreases passive transport), and gastric bypass surgery. – Renal losses can result from inhibition of sodium reabsorption or defects in Mg2+ reabsorption. Sodium reabsorption drives magnesium transport within the tubular segments. Thus loop and thiazide diuretics may enhance the deficiency. • Signs and symptoms of hypomagnesemia are non-specific and can be confused with signs and symptoms of hypokalemia, hypocalcemia, and metabolic alkalosis. They can manifest clinically as neuromuscular hyperexcitability, cardiac arrhythmias, and co-existing electrolyte abnormalities (hypokalemia, hypocalcemia). – Neuromuscular abnormalities: Excitability is manifest as tremor, twitching, tetany, and positive Chvostek and Trousseau signs. In the CNS, Mg2+ normally blocks NMDA receptors which function in excitation. Thus, it may result in generalized convulsions. – Cardiac arrhythmias: Mg2+ is necessary for all reactions involving ATP, including the Na+-K+-ATPase pump. Hypomagnesemia impairs function by impeding K+ efflux and increasing the resting membrane potential (less negative). This decreases the excitation threshold for an action potential. Additionally, the reduced intracellular K+ levels hinder repolarization. This results in increased irritability (ventricular arrhythmias: Ectopy, ventricular tachycardia and fibrillation, and Torsades de pointes) as well as conduction disturbances. EKG manifestations include widening of the QRS complex along with peaking of the T wave. Severe deficiency can flatten the T wave and may impair myocardial contractility. – Electrolyte derangements Hypokalemia: As previously mentioned, Mg2+ is necessary for proper Na+-K+-ATPase function and hypomagnesemia can result in reduced intracellular K+ levels. Additionally, hypomagnesemia is associated with renal potassium wasting in the loop of Henle (3). Hypocalcemia: Mg2+ is necessary for the release of parathyroid hormone (PTH); thus, a deficiency results in low PTH and calcium levels (3). • Association with other disease processes (does not imply causation) include: Mitral valve prolapse, fibromyalgia, diabetes, asthma, allergies, osteoporosis, and dysmenorrhea.

• Hypermagnesemia (>2.5 mEq/L) results from excessive exogenous intake/therapy, hemolysis, or impaired renal excretion/function. Hemolysis may increase levels due to increased intracellular stores. • Signs and symptoms of hypermagnesemia include weakness, hypotension, respiratory distress, arrhythmias, cardiac arrest, and coma. – Neuromuscular: Hypermagnesemia inhibits pre-synaptic acetylcholine release in skeletal muscles (manifests as weakness, hyporeflexia, and respiratory depression). In smooth muscle, Mg2+ antagonizes calcium and results in urinary retention and ileus. In the CNS, it can excessively block NMDA receptors which are involved in excitation. – Cardiac: Vascular smooth muscle dilation causes hypotension (Mg2+ antagonizes calcium). In the myocardium, it may hyperpolarize the cell membrane and cause sinus bradycardia, SA and AV nodal blocks, and cardiac arrest.

PERIOPERATIVE RELEVANCE

• Hypomagnesemia can be present in patients presenting for surgery. Signs and symptoms are often non-specific, or are overshadowed by hypokalemia or hypocalcemia. It may clinically manifest as ventricular and neuromuscular excitability. – Patients on certain medications (warfarin, birth control pills, lithium, laxative use), who are diagnosed with asthma, allergies, MVP, migraines, congestive heart failure, acute coronary events, psychiatric illness, or have had massive blood transfusions (citrate rich blood products), may have hypomagnesemia. Serum levels should be assessed. – Hypomagnesemia carries an increased risk for perioperative arrhythmias and resistance to neuromuscular blockade. – Treatment depends on the severity of clinical manifestations. In urgent and emergent situations such as Torsades de pointes, magnesium 1–2 grams IV contains 8–15 mEq and can be administered over 15 minutes followed by 1 g/h until serum levels have been normalized (4). • Hypermagnesemia can result from exogenous therapy, renal dysfunction, or hemolysis. It has several perioperative effects that the anaesthetist must be able to identify and treat appropriately. – Sedative effects of anesthetic drugs and volatiles may be compounded. – Hypotension (from reduced intracellular calcium levels in smooth muscle) can be compounded by anesthetics that directly vasodilate or reduce sympathetic discharge. – Muscle weakness (from inhibited release of synaptic neurotransmitters) may be compounded by neuromuscular blocking drugs (NMBD). Furthermore, the calcium antagonist effects of magnesium may potentiate NMBD. – Respiratory depression from muscle weakness may be compounded by anesthetics such as opioids, benzodiazepines, and volatiles. – Local anesthetic effects may be potentiated. • Preeclampsia: Magnesium is administered to parturients to reduce the incidence of eclampsia. Seizures are believed to be due to the excessive release of the excitatory neurotransmitter glutamate, which activates the NMDA receptor and leads to massive neural activity. Mg2+ competitively antagonizes glutamate (5). – Therapeutic levels are 5–7 mg/dL and are followed by physical exam (monitoring of deep

tendon reflexes) as well as laboratory testing. Deep tendon reflexes are reduced well before either respiratory depression or cardiac arrest occurs. They are easy to perform, non-invasive, and provide immediate information. – Toxic serum concentration levels differ in preeclamptics: Loss of patellar reflexes: 7–10 mEq/L Respiratory depression: 10–13 mEq/L Complete heart block: 15–25 mEq/L Cardiac arrest >25 mEq/L • Treatment of magnesium toxicity involves administering IV calcium gluconate. Calcium antagonizes the actions of magnesium in neuromuscular and cardiac functions. Additionally, in patients with normal renal function, IV diuretics may be used. In patients with abnormal renal function or renal failure, hemodialysis may be utilized. • Other therapeutic uses for magnesium include the management of patients with subarachnoid hemorrhage or asthma. • Plasma Mg2+ levels rise as renal function declines, because urinary excretion is its only regulatory system.

REFERENCES

1. Fawcett WJ, Haxby EJ, Male DA. Magnesium: physiology and pharmacology. Br J Anaesth. 1999; 83(2):302–320. 2. Wagner CA. Disorders of renal magnesium handling explain renal magnesium transport. J Nephrol. 2007;20(5):507–510. 3. Moe SM. Disorders involving calcium, phosphorus, and magnesium. Prim Care. 2008;35(2):215–237. 4. Yamamoto M, Yamagushi T. Causes and treatment of hypomagnesemia. Clin Calcium. 2007;17(8):1241–1248. 5. Lu JF, Nightingale CH. Magnesium sulfate in eclampsia and pre-eclampsia. Clin Pharmacokinet. 2000;38:305–314.

ADDITIONAL READING

• Agus ZS. Hypomagnesemia. J Am Soc Nephrol. 1999; 10:1616–1622. • Guillaume T, Krzesinski JM. Management of serum magnesium abnormalities. Rev Med Liege. 2003; 58(7–8):465–467.

See Also (Topic, Algorithm, Electronic Media Element) • Hypokalemia • Preeclampsia • Asthma • Ventricular tachycardia • Tachycardia • Ventricular fibrillation

CLINICAL PEARLS

• Hypomagnesemia may increase the risk of arrhythmias and neuromuscular excitability perioperatively. • Hypermagnesemia may compound sedative, hypotensive, respiratory depressant, and neuromuscular blocking effects of anesthetics. Local anesthetic effects may also be compounded.

MALIGNANT HYPERTHERMIA Edward Park, MD Harvey K. Rosenbaum, MD

BASICS DESCRIPTION

• Malignant hyperthermia (MH) is a pharmacogenetic disorder of the ryanodine receptor (RYR1). It is characterized by triggering of acute skeletal muscle hypermetabolism with increased oxygen consumption, as well as markedly increased production of carbon dioxide. • Triggers include halogenated volatile anesthetics, succinylcholine, and possible heat exposure or sustained strenuous exercise. EPIDEMIOLOGY Incidence

In 2009: 1:100,000 anesthetics. Prevalence

Molecular genetic testing of certain populations suggests a prevalence of 1:3,000. Morbidity/Mortality

Mortality is ~1%; it is increased when associated with significant medical co-morbidities, advanced age, the development of DIC, and heavier and more muscular builds. ETIOLOGY/RISK FACTORS

• Autosomal dominant pattern: Its heritability demonstrates incomplete penetrance and variable phenotypic expression. Sporadic, de novo mutations, without known positive family histories, are also known to occur. • Children <15 years of age; male:female ratio of 2:1; Caucasian race. • May be associated with congenital musculoskeletal defects such as clubfeet, idiopathic scoliosis, etc. PHYSIOLOGY/PATHOPHYSIOLOGY

• During normal skeletal muscle contraction, a propagated action potential reaches the L-type voltage-gated calcium channels (dihydropyridine receptors or DHPRs) along the transverse tubule system. DHPRs allow for intracellular calcium entry and cause a conformational change in coupled intracellular calcium channels (RYR1s). • RYR1s control the release of sequestered calcium from within the sarcoplasmic reticulum (SR) into the cytoplasm of skeletal muscle cells to continue the process of excitation– contraction coupling. This calcium binds to troponin complexes, allowing actin–myosin cross-linking and sarcomeric contraction to occur. • In MH, mutations in genes encoding for RYR1, DHPR, or other unidentified proteins lead to

disruption of the regulatory process that governs intracellular calcium movement from the SR and, likely, entry from the extracellular space. This leads to the excessive and unregulated release of calcium during excitation–contraction coupling. • When triggered, MH leads to sustained contractions/inability to relax the skeletal musculature, as the intracellular calcium remains outside of the SR. There is an increase in aerobic and anaerobic metabolism, creating a combined respiratory and metabolic acidosis as CO2 and lactate accumulate. Eventually, muscle tissue becomes hypoxic and rhabdomyolysis develops, leading to myoglobinuria and hyperkalemia as metabolites are released into the circulation.

PREVENTATIVE MEASURES

• Patients with proven or suspected susceptibility to MH: Attain previous anesthetic records, thoroughly review family history, and the presence of neuromuscular conditions. Additional laboratory work, cardiodiagnostic evaluation, or radiographic imaging beyond what is required for the work-up of the patient’s other underlying medical conditions is not warranted. • Avoidance of triggering agents: Strict avoidance of known triggers (succinylcholine, potent halogenated volatile anesthetics); consider alternative techniques to general anesthesia (conscious sedation, local infiltration, and regional anesthesia) if amenable to the surgical procedure in question. • Anesthesia machine: Remove (or temporarily disable) the vaporizers and all removable parts that may have been previously exposed to halogenated volatile anesthetics (CO2 absorber,

etc.). Consider an initial 5 minute flush of the circuit at high flows with the circuit attached during set-up. For the first 5 minutes of patient use, consider a fresh gas flow of 10 L/minute, with the filter attached, followed by an additional 5 minutes of flush at high flows with the circuit attached; for the first 5 minutes of patient use, consider a fresh gas flow of 10 L/min for the first 5 minutes of patient use, with the filter still attached, followed by maintenance of flows at >2 L/min for the duration of the case. • Prophylactic dantrolene: Controversial and probably unnecessary; may lead to clinically significant muscle weakness and, in patients with clinical myopathy, respiratory insufficiency. Scrupulous avoidance of halogenated volatile anesthetics and succinylcholine make an MH episode very unlikely. • Ambulatory setting: Ensure the availability of monitors and equipment necessary for the rapid escalation of care, should an MH crisis occur. The on-site presence of sufficient quantities of dantrolene (at least 10 mg/kg at a minimum adult dose or at least 36 vials of 20 mg doses) should also be confirmed. • Discharge from PACU: Following an uneventful surgery and anesthetic, the patient can be discharged home or to an appropriate hospital unit, after 2–4 hours of close postoperative observation.

DIAGNOSIS • Variable onset and presentation: Can range from a dramatic appearance shortly after induction of anesthesia, to a delayed and smoldering presentation hours into a case, or

within the first hour after emergence from general anesthesia. • Early clinical signs and symptoms represent increased metabolic demands. Unanticipated hypercarbia is the most reliable early sign; tachycardia and blood pressure lability (typically hypertension but hypotension can also occur); development of dysrhythmias; and masseter muscle or generalized muscular rigidity. • Later findings: Hyperthermia, sweating, skin mottling, hyperkalemia, myoglobinuria (appearing as cola-colored urine), mixed acidosis, elevated creatine kinase (CK) levels, and DIC. In fulminant cases, progression to malignant ventricular dysrhythmias and cardiac arrest may occur in <30 minutes after onset of an episode. • Masseter spasm: A potentially premonitory sign of an impending episode, and usually occurs after the use of succinylcholine; referred to by the term “jaws of steel.” The clinician can either cancel the case and consider referring the patient for workup of MH susceptibility or, alternatively, continue with the procedure using a non-triggering anesthetic technique while preparing to treat an episode of MH if it occurs.

DIFFERENTIAL DIAGNOSIS

• Acute processes that mimic the non-specific signs and symptoms of an MH crisis. Hypercarbia may be seen with insufficient minute ventilation; CO2 insufflation with

laparoscopic surgical techniques; subcutaneous emphysema; anesthesia circuit rebreathing from unacceptably low fresh gas flows, faulty inspiratory valves, or other equipment malfunction; embolic phenomena (increased PaCO2 to ETCO2 gradient); and infusions of

Dextrose 25% as part of total parenteral nutrition. Hyperthermia can be seen with scoliosis surgery, iatrogenic heating (warm fluids, heating blankets, etc.), and thyroid storm. • Hyperdynamic hemodynamic perturbations: Insufficient depth of anesthesia, thyroid storm, pheochromocytoma, tyramine crisis in a patient on an MAO inhibitor, neuroleptic malignant syndrome (NMS), serotonin syndrome, cerebral ischemia and/or intracranial hemorrhage, anticholinergic crisis, heat stroke, and recreational drug or other sympathomimetic toxin ingestion (i.e., cocaine, methamphetamines, or Ecstasy). Cardiovascular collapse can also be seen in an MH crisis, so septic shock and anaphylaxis should also be considered. • Muscular dystrophies, such as Duchenne or Becker muscular dystrophy, or some individuals with heat- or exercise-induced rhabdomyolysis, may develop fatal hyperkalemia and rhabdomyolysis after exposure to halogenated volatile anesthetics and succinylcholine.

TREATMENT • MH is a life-threatening medical emergency, and an immediate call for additional trained help should also be included in the first steps of treating a crisis. The surgeon should be notified of the patient’s condition, and the procedure should be terminated or concluded as expeditiously as possible while the patient is being resuscitated. • Discontinue the administration of all known triggering agents, switch to non-triggering anesthetic techniques, fluid resuscitation with cooled intravenous fluids, hyperventilate with 100% oxygen to 2 or 3 times normal minute ventilation, and administer dantrolene. • Dantrolene binds to RYR1 and restores the balance between SR calcium release and uptake

as well as calcium entry from the extracellular fluid. Thus, it decreases myofibrillar contraction (skeletal muscle relaxation) and “cools down" the hypermetabolic process. The initial recommended dose is 2.5 mg/kg; improvement in the patient’s clinical condition can begin in minutes. If not, additional boluses of 2.5 mg/kg can be administered until signs and symptoms have receded. Defervescence typically trails resolution of hypercarbia. Doses in excess of the manufacturer’s recommended total dose of 10 mg/kg may occasionally be required in the treatment of fulminant MH. • Monitors: Intravenous access with wide-bore cannulae should be obtained to aid in fluid resuscitation, drug administration, and frequent laboratory blood draws. Consider an arterial (blood gases) and central venous line, especially if the patient’s clinical condition deteriorates. If not already in place, an indwelling urinary catheter is mandatory to evaluate the brisk diuresis that occurs with fluid resuscitation and dantrolene therapy (as each vial contains 3 g of mannitol) as well as the presence of myoglobinuria. • Serial laboratory measurements: Serum electrolytes (especially potassium), renal and hepatic function panels, coagulation tests, arterial and/or venous blood gases, and serum myoglobin and CK levels. • Temperature: Follow closely and if >38.5°C, implement cooling measures: Resuscitate with chilled IV fluids and cool with ice packs, cool and dampened linens, and/or misted water with warm air fanning to promote evaporative heat loss. • Hyperkalemia: IV calcium and insulin with dextrose. Beta2-agonists may be considered after dantrolene is started, though they may aggravate any pre-existing tachyarrhythmia and should be used cautiously. Unstable cardiac rhythms may need to be cardioverted or treated with appropriate antiarrhythmic agents (e.g., amiodarone). Exercise caution in the treatment of wide QRS complex rhythms with lidocaine or procainamide, as this may be a sign of hyperkalemia and treatment with class 1 antiarrhythmics may result in asystole. • pH derangements (combined respiratory and metabolic acidosis): Hyperventilation along with bicarbonate administration (concurrent therapy for hyperkalemia) when pH <7.2. Emergent hemodialysis may be necessary for life-threatening hyperkalemia and/or acidosis. • Postoperative care: Intensive care unit, where supportive measures may need to be continued until the signs and symptoms have abated. Recrudescence can occur up to 24 hours after and requires dantrolene at doses of 1 mg/kg every 4–6 hours or via continuous infusion at 0.25 mg/kg/hr. Recrudescence reflects recurrent hypermetabolism and skeletal muscle injury. Signs can include increased ETCO2, paCO2, rapid spontaneous ventilation, myoglobinuria, rigidity, tachycardia, or hyperthermia. • Hospital discharge. There are no definitive laboratory values or criteria following an attack of MH. Typically, the patients should be asymptomatic and clinically stable, and can proceed towards an uneventful recovery at home within 2–3 days.

FOLLOW-UP • After a suspected case of MH presentation, the patient and family members need to be counseled regarding the potential future implications and ramifications of such a diagnosis. As the physician most familiar with MH and the patient’s clinical course, the anesthesiologist of record is the person most capable of beginning this process, and he/she

should write a letter for the patient’s personal medical records attesting to the events as they have unfolded and how the diagnosis of MH was made. • The Malignant Hyperthermia Association of the United States (MHAUS) is a nonprofit organization that provides information on MH for patients, family members, and health care personnel. It also offers medical assistance for elective and emergent questions and advice. • In vitro contracture testing (IVCT) exposes biopsied muscle to caffeine and halothane and tests for contracture. False-positive results can be as high as 15–20% under the North American Malignant Hyperthermia Registry protocol; 6–7% with the European protocol. False-negative results are believed to be very low. IVCT testing is limited by the cost of maintaining the relatively few centers that can perform this form of complex testing, as well as the invasive nature of the test. • An alternative to IVCT is molecular screening for genetic mutations known to produce susceptibility to MH. Although genes encoding for RYR1 proteins (located on chromosome 19) and DHPR proteins (located on chromosomes 1, 7, and 17) are most commonly implicated, there exists considerable heterogeneity in the genetic loci and linkage sites across known susceptible family lines. It must be emphasized that a negative mutation screen does NOT exclude MH susceptibility. Incomplete penetrance and variable phenotypic expression of MH raise the potential for a multi-genic predisposition towards MH susceptibility, with possible epigenetic influences leading to a relatively common final pathway.

REFERENCES

1. Allen GC, Larach MG, Kunselman AR. The sensitivity and specificity of the caffeinehalothane contracture test: A report from the North American Malignant Hyperthermia Registry. Anesthesiology. 1998;88(3):579–588. 2. Brandom BW. Ambulatory surgery and malignant hyperthermia. Curr Opin Anaesthesiol. 2009: 22(6):744–747. 3. Glahn KPE, Ellis FR, Halsall PJ, et al. Recognizing and managing a malignant hyperthermia crisis: Guidelines from the European Malignant Hyperthermia Group. Br J Anaesth. 2010; 105(4):417–420. 4. Prather Strazis K, Fox AW. Malignant hyperthermia: A review of published cases. Anesth Analg. 1993;77(2):297–304. 5. Wappler F. Anesthesia for patients with a history of malignant hyperthermia. Curr Opin Anaesthesiol. 2010;23(3):417–422.

ADDITIONAL READING

• Malignant Hyperthermia Association of the United States (MHAUS): www.mhaus.org. • The 24-hour telephone hotline of the MHAUS: (800) 644-9737 (MH-HYPER).

See Also (Topic, Algorithm, Electronic Media Element) • Trismus • Hyperthermia

CODES ICD9

995.86 Malignant hyperthermia ICD10 T88.3XXA Malignant hyperthermia due to anesthesia, initial encounter

CLINICAL PEARLS

• Diagnosis: Initially normal CK levels do NOT exclude MH. CK levels typically peak 8–12 hours following muscle injury and will slowly decline with successful treatment. If an MH episode has been promptly diagnosed and treated, the rise in CK level may be unimpressive. • Adverse drug reaction: Verapamil and/or diltiazem should NOT be used during treatment with dantrolene; hyperkalemia, myocardial depression, and cardiac arrest may result. • Monitoring: Hyperkalemia may also appear after hypermetabolism has been controlled. The authors recommend checking serum potassium levels 1 and 2 hours after initiating dantrolene therapy, and then every 8 hours for 24 hours, or as clinically indicated by ECG signs or evidence of recrudescence.

MARIJUANA ABUSE

Menelaos Karanikolas, MD, MPH

BASICS DESCRIPTION

• Marijuana (MJ) is derived from Cannabis sativa, a member of the Cannabaceae plant family. MJ is known by several different names, such as bhang, cannabis, ganja, grass, hash or hashish, pot and weed. – Chronic cannabis use is defined as almost daily use over a period of years. – Cannabis dependence is defined by impaired control over MJ use and continuing use despite harm. • Marijuana contains over 60 compounds, of which several have psychoactive properties, but delta-9 tetrahydrocannabinol (THC) is the primary component (1)[B]. • MJ can be smoked as a cigarette (joint), a cigar (blunt) or in a water pipe, but can also be brewed as tea, mixed in food, or even (rarely) injected. • Dronabinol (Marinol) and nabilone (Cesamet) are FDA-approved medications containing cannabinoid-based synthetic compounds. Legitimate medical uses include: – Analgesia, especially for neuropathic pain (2)[A]. – Antiemetic effects (patients receiving chemotherapy). – Increased appetite (cancer or AIDS patients). – Treatment of spasticity and glaucoma.

PHYSIOLOGY PRINCIPLES

• The THC content of cannabis has increased markedly, from <2% in 1980 to 8.5% in 2006. – THC acts on the CB1 and CB2 cannabinoid receptors. – When smoked, THC is rapidly absorbed through the lungs into the circulation and carried to the brain and other organs. The peak CNS effect occurs in 15 minutes, and can last for 2–4 hours (1)[B]. – When ingested orally, THC bioavailability is lower and onset is slower, but duration is longer.

DISEASE/PATHOPHYSIOLOGY

• Central nervous system: – Acute effects include: Relaxation, euphoria, heightened or distorted perception of space or time, nystagmus, tremor, impaired coordination, headaches and hyperemesis. Anxiety, panic, dysphoria, hallucinations, or sedation can also occur. – Chronic effects include: Lack of motivation, impaired memory and learning, and increased risk of psychotic disorders. – Withdrawal symptoms include irritability, impaired sleep, reduced appetite, and anxiety. These symptoms subside after 1–2 weeks of abstinence. • Airway:

– Acute effects include: Uvular edema or laryngospasm, leading to airway obstruction. – Chronic effects include: Airway inflammation, and possibly increased risk of airway cancer. • Cardiac: – Acute effects include: Coronary artery spasm resulting in myocardial ischemia, myocardial infarction or ventricular arrhythmias (in MJ users with patent coronary circulation). – Chronic effects include: Vasodilatation, tachycardia, increased myocardial oxygen demand, increased risk of myocardial ischemia or infarction. • Respiratory: – Acute effects include: Bronchodilatation, increased carboxyhemoglobin levels (up to 5 times higher compared to tobacco smokers). – Chronic effects include: Airway inflammation, as well as increased mucus secretion and edema, thereby predisposing to increased bronchial irritability. Emphysema and secondary pneumothorax have been reported in young chronic MJ users (3)[C]. There is an increased risk of pulmonary infection due to impaired pulmonary defense and possible MJ contamination by Aspergillus, Salmonella, or even fecal matter. Additionally, lung cancer has been associated with chronic MJ use. • Reproductive problems include reduced testosterone, reduced testicle size, impaired sperm motility, lower libido, impotence, and menstrual abnormalities.

Pediatric Considerations

Chronic MJ use may cause fetal intrauterine growth retardation (IUGR) due to decreased utero-placental perfusion. Pediatric Considerations

• Children exposed to maternal MJ use during gestation manifest mild developmental abnormalities and are at increased risk for non-lymphoblastic leukemia (10-fold). • MJ use by children is a real concern, and should not be overlooked, especially in pediatric patients over the age of 12.

PERIOPERATIVE RELEVANCE

• History: – Obtain a detailed and complete history of substance abuse in every patient. – Patients may attempt to hide their drug use from their family and their doctor, thus, questioning about drugs should be conducted in private, as people may not be truthful when questioned in the presence of friends or family. Unfortunately, marijuana use is very common, especially among young patients, even pediatric patients. – Possible red flags include an unexplained worsening of performance at work or school, as well as problems with social functioning or relationships, and loss of interest in pleasant activities. However, within the constraints of the perioperative period, such detailed history may not always be elicited. – Young patients with emphysema or spontaneous pneumothorax should be questioned about MJ abuse (3)[C]. • Labs: Urine, blood, or hair drug testing can confirm or exclude MJ use. Due to high lipid solubility, THC may remain in the body for up to 30 days, and can be detected in the urine

for several weeks or even months. • Antidote: There is no clinically available specific antidote or antagonist for THC, and therefore treatment of acute intoxication is symptomatic. • Central nervous system: Acute MJ intoxication decreases the need for anesthetic drugs, whereas chronic use may increase requirements for anesthetic medications, such as propofol (4)[B]. • Airway: Consider using dexamethasone as prophylaxis against upper airway edema. Topical use of local anesthetics suppresses laryngeal reflexes and may reduce the risk of laryngospasm. • Cardiac: Because MJ intoxication can increase the heart rate, drugs that cause tachycardia (ketamine, pancuronium or rocuronium, atropine, ephedrine, and epinephrine) should be avoided or used cautiously. • Respiratory: Consider using a laryngeal mask airway (LMA) rather than intubation, to reduce airway stimulation and trauma. Similar to asthma and reactive airway disease, limit bronchospastic triggers: Ensure that the patient is deep prior to airway instrumentation, consider introducing volatile anesthetics during bag mask ventilation, maintain an adequate depth of anesthesia, avoid histamine releasing drugs, and consider a deep extubation, if appropriate.

REFERENCES

1. Bryson EO, Frost EAM. The perioperative implications of tobacco, marijuana, and other inhaled toxins. Int Anesthesiol Clin. 2011; 49:103–118. 2. Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011. doi: 10.1111/j.1365– 2125.2011.03970.x 3. Beshay M, Kaiser H, Niedhart D, et al. Emphysema and secondary pneumothorax in young adults smoking cannabis. Eur J Cardiothorac Surg. 2007; 32:834–838. 4. Flisberg P, Paech MJ, Shah T, et al. Induction dose of propofol in patients using cannabis. Eur J Anaesthesiol. 2009;26:192–195. 5. Arendt M, Munk-Jørgensen P, Sher L, et al. Mortality among individuals with cannabis, cocaine, amphetamine, MDMA, and opioid use disorders: A nationwide follow-up study of Danish substance users in treatment. Drug Alcohol Depen. 2011;114:134–139.

ADDITIONAL READING

• Hernandez M, Birnbach DJ, Van Zundert AA. Anesthetic management of the illicitsubstance-using patient. Curr Opin Anaesthesiol. 2005;18:315–324. • Initiation of Marijuana Use: Trends, Patterns and Implications, published by SAMSHA, US Department of Health and Human Services, accessed online on June 9, 2011 at: http://oas.samhsa.gov/MJinitiation/chapter3.htm • Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet. 2009;374(9698):1383–1391.

See Also (Topic, Algorithm, Electronic Media Element)

• Cocaine abuse • Alcohol abuse • Smoking • Asthma

CODES ICD9

• 304.30 Cannabis dependence, unspecified • 305.20 Cannabis abuse, unspecified ICD10

• F12.10 Cannabis abuse, uncomplicated • F12.20 Cannabis dependence, uncomplicated

CLINICAL PEARLS

• The constraints of the perioperative period and nature of the patient–anaesthetist relationship make diagnosis and counseling difficult, if not impossible. Ideally, management should include education about the adverse effects of MJ, evaluation about the use of other drugs and alcohol, and the treatment of coexisting psychiatric disorders. However, if use is suspected or admitted, informed consent should discuss and describe the potential for adverse effects and increased perioperative risk. • The CNS, airway, pulmonary and cardiovascular effects of MJ are significant perioperative concerns. • Additionally, MJ is frequently combined with other substances of abuse such as alcohol, benzodiazepines, amphetamines or cocaine, and is associated with significant psychiatric and physical comorbidities. • Epidemiology – Incidence According to data recently published by the US Department of Health and Human Services, 2 million Americans a 12 and older used MJ for the first time in 1999. Incidence of MJ use is higher, and the mean age of the first MJ use is lower in males, compared to females. There is a worrisome trend of starting MJ use at a younger age. In 1999, the mean age for MJ initiation was 17.2 years for whites, 16.4 years for blacks and Hispanics, 18.8 for Asians, and 15.8 years for those reporting more than one race. – Prevalence: MJ is the illicit substance most often used in the US and worldwide: Over 50% of people in the US have used MJ at some point during their lifetime. In the US, 15.7% of 8th graders, 32.3% of 10th graders, and 42.0% of 12th graders have used MJ. 10–20% of 18–25 year-old patients use MJ. In Australia, 9.8% of injured drivers sent to the hospital are THC-positive.

10% of people experimenting with MJ become daily users and 20–30%, weekly users. Prevalence is higher among patients with psychiatric disease and/or chronic pain. – Morbidity: Compared to tobacco, marijuana smoking contains higher concentrations of airway irritants and carcinogens. Chronic MJ use increases the risk of throat and lung cancer, probably at a younger age compared to tobacco abuse. – Mortality: The fatal human dose is estimated to be 15–70 grams. Deaths related to cannabis overdose are unlikely, but cannabis is often detected along with other substances in drug overdose deaths. Compared to the general population, overall mortality is increased five-fold in MJ users, likely due to road, industrial or other accidents, violent injuries and homicides (5)[B]. Cannabis body packing, in an attempt to smuggle large quantities of cannabis across international borders, has been reported to cause fatal colonic perforation.

MASTECTOMY Edna Ma, MD

BASICS DESCRIPTION General

• A mastectomy is a surgical procedure to partially or completely remove one or both breasts. This operation is performed for either excision of a diagnosed cancerous tumor or prophylactically (to prevent cancer when there is a genetic predisposition). • A “lumpectomy” or “wide local excision” involves surgical excision of suspected tumor and the margin of the surrounding normal breast tissue, while conserving as much normal breast tissue as possible. • For staging purposes, the surgery may involve an axillary lymph node exploration and excision, called “sentinel lymph node biopsy” (1). The sentinel lymph node is the first axillary lymph node that would demonstrate any metastatic disease, given the drainage of lymph from the breast. • Some patients elect for immediate reconstruction after the mastectomy (under the same anesthetic), which could involve tissue grafting with either the latissimus dorsi flap or the transverse rectus abdominis myocutaneous (TRAM) flap or insertion of a tissue expander. Position

Supine with the arm prepped free for access to the axilla. Incision

• Near the site of the overlying tumor • May be periareolar if a nipple-sparing technique is used.

Approximate Time

Varies depending on the extent of disease and reconstruction: 1–5 hours. EBL Expected

Ranges from <50 to several hundred milliliters, depending on the extent of reconstruction. Hospital Stay

Lumpectomies may be discharged on the same day. Special Equipment for Surgery

• If a sentinel lymph node biopsy is scheduled, a blue dye (by surgeon) or a small amount of radioactively labeled tracer (by radiologist) is injected near the tumor in order to stain the lymph vessels and nodes so that the sentinel lymph node is more easily visualized. • A Geiger counter is utilized intraoperatively to locate the lymph node with the most active

uptake.

EPIDEMIOLOGY Incidence

• Women: 124.2 per 100,000 per year. There is an overall decreasing rate, which is associated with the discontinuation of hormone replacement therapy (2). • Men: Accounts for 1% of all breast cancer.

Prevalence

Most frequently diagnosed cancer in women in the US (not including skin cancer). Morbidity

Breast cancer rates decreased by about 2% between 1998 and 2007 (3). This decrease was only among women aged 50 years and older. Mortality

• Second-leading cause of cancer death among women in the US. • Fortunately, the rate has been decreasing since 1990 at an overall rate of 2.3% per year (3.3% for women aged 40 to 50 years). This decrease is largely attributed to the combination of mammography screening with improved treatment. • Approximately 1 in 35 women die from breast cancer in the US.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients can present with anxiety over their diagnosis or potential diagnosis. • Pain and postoperative nausea and vomiting are common issues in this patient population. Multimodal, opiate-sparing regimens have been advocated and studied (including paracetamol, dextromethorphan, celecoxib, gabapentin, dexamethasone, total intravenous anesthesia, and intraoperative ondansetron).

PREOPERATIVE ASSESSMENT SYMPTOMS

Varies widely from no symptoms to skin changes, fatigue, palpable mass, and rarely pain from cancer that has metastasized to the bone. History

Risk factors include age (>50 years old), family history (first degree relative), early menarche, late menopause, late first pregnancy, and nulliparity, which are presumed to prolong estrogen exposure to the breasts. Signs/Physical Exam

• May include changes in the overlying skin (“peau d’orange”), nipple discharge, or palpable mass identified by the patient or on routine examination. • Lesions may also be identified by a screening mammography (2).

MEDICATIONS

• Chemotherapeutic agents: Doxorubicin, cyclophosphamide, paclitaxel, docetaxel, cyclophosphamide. • Hormone therapy: Tamoxifen (mixed estrogen agonist–antagonist) or letrozole (an aromatase inhibitor to stop estrogen production). • Anti-emetics for chemotherapy: Ondansetron or metoclopramide.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Standard screening labs as dictated by the patient’s history (e.g., CBC, chemistries). • Advanced stages or recent chemotherapy may be associated with pancytopenia. • BRCA1 and BRCA2 are susceptibility genes associated with breast cancer. HER2/neu, a proto-oncogene, is also expressed in breast cancer. CONCOMITANT ORGAN DYSFUNCTION

• In addition to regional lymph node involvement, metastatic disease may include the bone, liver, and lungs. • Assessment for organ damage from chemotherapeutic agents (doxorubicin, adriamycin).

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics should be considered and titrated to effect. • Preoperative hydration to reduce postoperative nausea and vomiting (PONV) may be appropriate.

Special Concerns for Informed Consent

• Patients often arrive earlier to have the radiology department either place a wire to localize the tumor site or for lymphoscintigraphy involving injection of radionuclide. Under these circumstances, ensure that consents for surgery are completed and signed prior to the administration of anxiolytics. • If deep sedation is performed for lumpectomies or biopsies, discuss appropriate sedation goals.

Antibiotics/Common Organisms

• Biopsies and lumpectomies may not require prophylaxis. However, needle localization and wire placement require prophylaxis. • Broad spectrum, 3rd generation cephalosporin such as cefazolin can protect against skin flora.

INTRAOPERATIVE CARE Choice of Anesthesia

• Deep sedation may be appropriate in lumpectomies or biopsies. • General anesthesia with an LMA or ETT is appropriate for mastectomies. • Reconstructive procedures often necessitate neuromuscular blockade to provide a still surgical field; hence ETT is chosen. • Cervical epidural anesthesia (CEA) as the sole technique has been discussed in the literature as having the potential benefit of good analgesia and avoidance of PONV, as well as lower overall cost. However, it is seldom practiced due to its reported complications (4). • Thoracic epidural anesthesia (TEA) as a sole technique has also been discussed in the literature for its potential benefit of improved postoperative pain relief and recovery as well as lower cost than general anesthesia for modified radical mastectomies (5).

Monitors

• Standard ASA monitors. • Avoidance of intravenous access and non-invasive blood pressure (NIBP) in the arm ipsilateral to the surgical site, to minimize the risk of lymphedema or interference with the surgical field. • If an indwelling, tunneled catheter is present for chemotherapy, it may be accessed. Consider aspirating heparin before flushing the port.

Induction/Airway Management

• Deep sedation: Titrate to a level appropriate for local anesthetic injection. • GA: Intravenous induction; a mask induction may be performed if IV access is difficult or limited.

Maintenance

• Balanced intravenous or volatile anesthetic. Total intravenous anesthesia with a propofolbased technique may reduce PONV. • Dexamethasone for PONV should be administered after induction to avoid rectal itching or burning. • If isosulfan blue dye is injected by the surgeon, a transient spurious decrease in the pulse oximetry reading may result from systematic absorption.

Extubation/Emergence

Standard extubation criteria apply.

POSTOPERATIVE CARE BED ACUITY

• For uncomplicated mastectomy, a floor bed is usually adequate. • Free TRAM reconstructions require a higher level of care.

ANALGESIA

• PCA • Indwelling catheter delivering local anesthetic in the wound (e.g., “On-Q PainBuster” pump).

• Thoracic epidural. • Intercostal nerve blocks.

COMPLICATIONS

• Positive margins requiring reincision. • Infection. • Hematoma or seroma. • Lymphedema. • Failed reconstruction. • Postoperative nausea and vomiting.

PROGNOSIS

Prognosis is dependent on its stage. The 5-year survival for stage 1 (T1N0M0) is 92% and for stage IV (any T, any N, M1) is 14%.

REFERENCES

1. Gerber B, Krause A, Reimer T, et al. Skin-sparing mastectomy with conservation of the nipple–areola complex and autologous reconstruction is an oncologically safe procedure. Ann Surg. 2003;238(1):120–127. 2. Ravdin PM, Cronin KA, Howlader N, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007;356:1670–1674. 3. merican Cancer Society. How Many Women Get Breast Cancer? Overview: Breast Cancer. Atlanta, GA: American Cancer Society; 2009. 4. Gartner R, Kroman N, Callesen T, et al. Multimodal prevention of pain, nausea and vomiting after breast cancer surgery. Minerva Anesthesiol. 2010; 76(10):805–813. 5. Yeh CC, Yu JC, Wu CT, et al. Thoracic epidural anesthesia for pain relief and postoperation recovery with modified radical mastectomy. World J Surg. 1999;23(3):256–260. 6. Lewis JW, Shavit Y, Terman GW, et al. Apparent involvement of opioid peptides in stressinduced enhancement of tumor growth. Peptides. 1983;4:635–638. 7. Gottschalk A, Sharma S, Ford J, et al. The role of the perioperative period in recurrence after cancer surgery. Anesth Analg. 2010;110:1636–1643. See Also (Topic, Algorithm, Electronic Media Element) • Postoperative nausea and vomiting. • Epidural

CODES ICD9 174.9 Malignant neoplasm of breast (female), unspecified ICD10

• C50.919 Malignant neoplasm of unsp site of unspecified female breast • C50.929 Malignant neoplasm of unsp site of unspecified male breast

CLINICAL PEARLS

• Potential anesthetic interventions that can attenuate the surgical stress response and tumor genesis include: Use of regional anesthesia, COX inhibition (e.g., celecoxib, indomethacin), normothermia, and beta-blockers (7). – Regional anesthesia has been shown to reduce metastasis and optimize post-operative analgesia in animal studies. Surgical stress and general anesthesia may suppress the immune system, and activate the neuroendocrine and sympathetic nervous systems. – Immunosuppression, and thus promotion of cancer progression, is thought to be mediated by cytokines, chemokines, prostaglandins, and COX. Additionally, pain stimulates the hypothalamic—pituitary–adrenal axis and can activate the sympathetic nervous system. This can result in immunosuppression and suppression of natural killer T-cell activity, thus promoting tumor development in animal studies (6).

MECHANICAL CIRCULATORY ASSIST DEVICES (MCAD) Jonathan D. Leff, MD Daniel A. Lazar, MD

BASICS DESCRIPTION General

• Mechanical circulatory assist devices (MCADs) can partially or completely support the circulation of a patient with a failing heart. Indications for its placement include: – “Bridge to Recovery”: Utilized for acute cardiac decompensation. Considered “rescue” therapy in cardiogenic shock, myocardial infarction, myocarditis, postcardiotomy, heart failure. – “Bridge to Transplant”:Offers support until a donor heart becomes available. – “Destination Therapy”: Approved by the FDA in 2002 as a permanent alternative to heart transplantation in patients who are not otherwise candidates. • Pump classification: – Pulsatile flow (first generation): Large devices that are volume dependent, have unidirectional valves, and are pneumatically or hydraulically driven. – Continuous flow (second and third generations): Have several advantages including a smaller, simpler design with less mechanical parts to malfunction or replace; as well as less sheer forces on blood. They can also be implanted in smaller patients (1). There are 3 types: Axial pump: Utilizes helically shaped blades that propel blood to accelerate along the axis of the rotor. Centrifugal: The rotors are shaped to accelerate flow circumferentially and towards the outside of the pump (2). Non-contact magnetic bearing: Provides for no-touching parts within the pump since the rotors are suspended between two magnetic components. • Anticoagulation with either heparin/warfarin or antiplatelet therapy is needed to prevent thrombosis with most MCADs. This therapy is initiated soon after implantation of the device and continued throughout the duration of support. • The pump and its cannulas/connections are placed during “open heart surgery” after the institution of cardiopulmonary bypass (CPB). The pump is placed within the abdominal wall or pericardium. Cardiac inflow and outflow cannulas are positioned as follows: – Left ventricular assist device (LVAD): Inflow: Left atrium or left ventricle apex. Outflow: Ascending aorta, descending aorta. – Right ventricular assist device (RVAD): Inflow: Right atrial appendage. Outflow: Pulmonary artery. – Biventricular assist device (BIVAD) have RVAD and LVAD connections. – Percutaneous: Impella (Abiomed Danvers, Massachusetts)-consist of one cannula that is

inserted via the femoral artery and through the aortic valve; precludes the need for CPB. TandemHeart (CardiacAssist Inc. Pittsburgh, PA)- consists of two percutaneous cannulas with the inflow placed across the atrial septum to provide left heart drainage.

Position Supine

Incision

Median sternotomy or percutaneously in the catheterization lab. Approximate Time

Variable and dependent on factors such as previous sternotomy. EBL Expected

• Bleeding following device implantation can be substantial in the perioperative period (~1–3 L). • Coagulopathy may also be observed immediately after placement secondary to the device’s damaging effect on platelets and coagulation factors.

Hospital Stay

Median discharge time 27–28 days, ranging from 8 days to 12 months (3).

Special Equipment for Surgery

• Device: The pump and cannula are implanted; the computer controller, power pack/battery, and a reserve power pack are external. • Cardiopulmonary bypass circuit. • Transesophageal echocardiography.

EPIDEMIOLOGY Incidence

• Heart failure affects 4.8 million Americans; of which ∼250,000 are considered refractory to medical therapy (4). • Less than 3,000 available hearts for transplant.

Prevalence

Annually, over 1,000 LVADs are placed. Morbidity

Related to device malfunction, coagulopathy, reoperation, end-organ dysfunction, right ventricle failure, pulmonary hypertension, infection, AAPACHE score, center experience, and the extent of psychosocial support. Mortality

Most common causes of death post-LVAD implantation: Sepsis, multiorgan failure, right heart failure, device failure.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Although patients may present from home, MCADs are often placed on inpatients with decompensated congestive heart failure (CHF) or acute insults. They usually have multiple co-morbidities, are catecholamine dependent, and have slow circulation times. • Careful fluid management is required secondary to pulmonary congestion during the preoperative period. Post-LVAD implantation, the patient is preload/volume dependent for their cardiac output. • Prepare for coagulopathy by administration of antifibrinolytics and have blood products easily accessible. • A transesophageal echocardiogram (TEE) is performed, following induction of anesthesia to assess for MCAD suitability (patent foramen ovale, right ventricular function, tricuspid regurgitation, aortic insufficiency, left ventricular thrombus) as well to assist with cannula placement and device management. • When placing an LVAD, the right ventricle needs special attention and pharmacologic support.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Dyspnea, orthopnea, paroxysmal nocturnal dyspnea. • Chest pain.

History

Ischemic and/or non-ischemic cardiomyopathy. Signs/Physical Exam

Peripheral edema, elevated jugular venous pressure, S3 gallop MEDICATIONS

• CHF therapy: Diuretics, angiotensin converting enzyme (ACE) inhibitors, beta blockers, aldosterone antagonist, nitrates, digoxin, etc. • Many patients with CHF are on anticoagulation therapy such as: Aspirin, heparin, warfarin, and clopidogrel. These drugs, while useful in preventing thrombosis and ischemia, increase the risk of bleeding and may require reversal. • Intotropes in acute decompensation.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, BUN, Cr. • CBC, PT, PTT, INR, fibrinogen, D-dimer, etc. • Type and cross • Electrocardiogram • Chest X-Ray, chest radiography, echocardiography, coronary angiography

CONCOMITANT ORGAN DYSFUNCTION

• Pulmonary hypertension. • Renal insufficiency, liver failure, peripheral vascular disease, diabetes.

TREATMENT PREOPERATIVE PREPARATION Premedications

If on vasopressors/inotropes, continue as needed throughout induction and pre-CPB. Special Concerns for Informed Consent

Management of defibrillators, pacemakers, and Cardiac Resynchronization Therapy (CRT) includes disabling shock capabilities and placement of external defibrillator pads. Pacemakers, if present, should be switched to an asynchronous mode. Antibiotics/Common Organisms

• Wide spectrum antibiotics are administered in the preoperative period including: Vancomycin, rifampin, and fluconazole. • The most frequent organisms in patients with MCADs are: Staphylococcus epidermidis and Staphylococcus aureus. Other less common organisms include: faecalis and methicillinresistant Staphylococcus epidermidis [MRSE], methicillin-susceptible Staphylococcus aureus [MSSA] and Corynebacterium striatum, and methicillin-susceptible Staphylococcus epidermidis [MSSE] and Corynebacterium species.

INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia with endotracheal tube Monitors

• Standard ASA monitors. • Preinduction arterial line for beat-to-beat BP monitoring and frequent blood sampling. • Large bore peripheral intravenous access for fluid resuscitation in patients without central access. • Central venous access (8.5 or 9F) with CVP monitoring capability and multiple infusion ports for the infusion of vasoactive drugs. • Pulmonary artery catheter (PAC) allows for monitoring of pulmonary artery pressure, cardiac output, mixed venous analysis, and pacing capability. In the postoperative period, it is utilized to manage right ventricular function. • Intra-operative TEE to evaluate for: – Aortic insufficiency: Can lead to a circulatory loop between the left side of the heart and the aortic valve as blood from the outflow cannula passes retrograde into the left ventricle through an incompetent aortic valve rather than flowing in an antegrade manner to the body.

– Right heart and tricuspid valve functions: Left ventricular decompression leads to an increase in cardiac output and right ventricular volume overload (increased right ventricular preload) which may not be tolerated by the right heart. – Intracardiac shunts: A patent foramen ovale (PFO) can result in left ventricular unloading and right-to-left shunting. – Specific to CPB: De-airing as well as assessment of aortic plaques, placement of cannulas, and left ventricle decompression. • Near infrared spectroscopy (NIRS) is useful to assess frontal cortex oxygenation. Pulse oximetry is often difficult, following implantation of a continuous flow device and cerebral oximetry can provide information in regards to cerebral oxygen saturation. The use of the technology is variable among institutions.

Induction/Airway Management

• Individualized to each patient and slowly titrated to effect and hemodynamic goals; fentanyl, etomidate, and/or ketamine are commonly utilized. In general, heart failure patients have slow circulation time and are dependent upon catecholamines to support their circulation. Excessive blunting of this demand can lead to severe hypotension. • Emergency drugs such as epinephrine and ephedrine may serve to enhance the impaired cardiac output during induction. Coronary perfusion pressure should be maintained to ensure an adequate myocardial oxygen supply.

Maintenance

• Pre CPB. – Volatile anesthetics as tolerated. Nitrous oxide can increase pulmonary vascular resistance and is best avoided. – Opioids: High dose techniques may bestow hemodynamic stability. – Echocardiographic evaluation of appropriate LV decompression. – Careful attention to fluid management. – Heparinization. • Post CPB: – Patients may be vasodilated and require vasoactive drugs. – Patients are preload-dependent; maintenance of an adequate volume status is imperative for adequate cardiac output. – Right heart support for LVAD. – Monitor mechanical assist device flows. – Echocardiographic evaluation of the heart. – Pulmonary vasodilators such as nitric oxide or milrinone may be required for pulmonary hypertension and to decrease RV afterload. – Address coagulopathies which often require the use of blood products (i.e., FFP, platelets, and cryoprecipitate). This therapy can be guided with the use of thromboelastography (TEG). There is always a risk of clotting a device and therefore it is best to utilize guided therapy for administration of blood products and begin anticoagulation on postoperative day 1 or 2. – ICD reactivation.

Extubation/Emergence

May be extubated in the ICU when criteria are met.

POSTOPERATIVE CARE BED ACUITY

• ICU • Anticoagulation with heparin is started post-operatively when bleeding is stabilized and transitioned to Warfarin. • Continue antibiotics. • Aseptic technique should be maintained around the driveline when changing dressings.

ANALGESIA

Pain is typically moderate to severe and managed with PCAs. COMPLICATIONS

• Thromboembolism within the pump can lead to malfunction or cerebral vascular events. • Infections: Occur most commonly in the driveline or the abdominal wall pocket. • Hemorrhage from coagulopathies. • Right heart failure. • Device malfunction. • Cerebral air embolism. • GI bleeding.

PROGNOSIS

(LVAD) survival range 86%, 56%, 33% at 30 days, 1 year and 2 years, respectively. More recent devices continue to show improvement in survival.

REFERENCES

1. Slaughter MS, Rogers JG, Milano CA. Advanced heart failure treated with continuous-flow left ventricular assist device. NEJM. 2009;361:2241–2251. 2. Hensley FA, Martin DE, Gravlee GP. Cardiac Anesthesia. 4th ed. Philadelphia, PA: Lippincott Williams and Wilkins, 2008;587–589. 3. Leitz K, Long JW, Kfoury AG. Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era. Circulation. 2007;116:497–505. 4. Goldstein DJ, Oz MC, Rose EA. Implantable left ventricular assist devices. NEJM. 1998;339:1522–1533. 5. iha H, Netuka I, Kotulak T, et al. Anesthesia management of a patient with a ventricular assist device for noncardiac surgery. Semin Cardiothorac Vasc Anesth. 2010;14(1):29–31. See Also (Topic, Algorithm, Electronic Media Element) • Heart transplantation. • Congestive heart failure.

• Cardiopulmonary bypass. • Antifibrinolytics

CODES ICD9

428.9 Heart failure, unspecified ICD10 I50.9 Heart failure, unspecified

CLINICAL PEARLS

Patients may present to the operating room with MCADs for noncardiac procedures. Preoperative care involves consulting with MCAD management personnel, detailed assessment of end-organ dysfunction, appropriate antibiotic prophylaxis, deactivation of implantable cardioverter-defibrillator for the time of surgical procedure, and choosing the anesthesia type. Intraoperative monitoring for pulsatile devices do not require special monitoring; whereas devices with nonpulsatile blood flow require the placement of an arterial line (pulse oximetry and noninvasive blood pressure measurement are not reliable). Patients are exquisitely dependent on preload to maintain adequate cardiac output and need careful fluid management. Anesthetic agents can decrease systemic vascular resistance and need to be carefully titrated; vasoconstrictors should be readily available for administration. Management of anticoagulation needs to be discussed with the surgeon and cardiologist (5).

MEDIASTINOSCOPY Teresa L. Moon, MD

BASICS DESCRIPTION General

• A mediastinoscopy facilitates mediastinal exploration in a less invasive manner than a sternotomy or thoracotomy. • The lungs possess a rich lymphatic system that drains into the subcervical, paratracheal, and supracervical nodes. • The procedure is mainly performed to biopsy mediastinal lymph nodes to assess the spread of bronchogenic carcinoma; it is considered as the gold standard for mediastinal lymph node staging. – A cervical approach can be employed for pretracheal, paratracheal, and anterior subcarinal nodes. – A transthoracic or anterior approach is commonly used for aortopulmonary nodes. • The procedure entails dissection between the trachea and pretracheal fascia. A mediastinoscope (lighted instrument) is inserted and advanced along this plane to the level of the carina; it remains behind the aortic arch, the innominate artery, and the innominate vein. – Needle aspiration and biopsy may be performed – Clips may be placed to facilitate X-ray visualization – A drain may be inserted to allow for blood, fluid, or air collection – Often performed in conjunction with a bronchoscopy • Other indications for mediastinoscopy include: – Biopsies when sarcoidosis, Hodgkin’s disease, or tuberculosis are suspected – Excision of mediastinal masses Position

• Supine • Reverse Trendelenburg • Shoulder roll with neck extension

Incision

• Suprasternal transverse for cervical mediastinoscopy; approximately 1–2 cm above the sternum and 4 cm long. • Parasternal, usually left second interspace for transthoracic mediastinoscopy (Chamberlain’s procedure or anterior mediastinotomy). Approximate Time Less than one hour

EBL Expected

• Minimal • Risk of significant hemorrhage if vascular injury occurs.

Hospital Stay

Outpatient versus 23-hour observation. Special Equipment for Surgery

Mediastinoscope: A handle with a blade that appears similar to a laryngoscope (Miller blade). The instrument is lighted and can either have a lens that allows for direct visualization or can be attached to a cable that allows for video-assisted display onto a monitor screen. Biopsy instruments are passed through a large channel alongside the scope. EPIDEMIOLOGY Prevalence

For use in lung cancer evaluation most commonly Morbidity

• Bleeding (0.73%) • Pneumothorax (0.66%) • Recurrent laryngeal nerve injury (0.34%) • Cerebral ischemia • Esophageal perforation • Pleural tear • Laceration of trachea • Acute tracheal collapse • Tension pneumomediastinum

Mortality

Overall: 0.09%

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Airway collapse may result secondary to the presence (and size) of the mediastinal mass. Patients should be evaluated by history and symptoms as well as imaging or pulmonary flow volume loops to determine this potential. If airway collapse is likely with muscle paralysis, it is best to keep the patient spontaneously ventilating. • The anaesthetist should have a clear understanding of the anatomy of the procedure. There are multiple large vessels in the mediastinum, and potential vascular injury can be catastrophic.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Dyspnea that is positional may suggest an anterior mediastinal mass that is compressing an

airway structure • Cough

History

• Usually performed for lung cancer with enlarged nodes or mediastinal lymph node enlargement due to lymphoma, thymoma, or retrosternal goiter. • Commonly performed for sarcoidosis, tuberculosis, or therapeutic excision of a mediastinal mass. • Therapy: Chemotherapy and/or radiation.

Signs/Physical Exam • Tracheal deviation • Vein engorgement

MEDICATIONS Variable

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Chest CT: To look for any airway obstruction or distortion, or any vascular (superior vena cava) obstruction • Carotid studies: To determine if there is an increased risk for cerebral malperfusion during surgical manipulation • Type and cross: Blood should be available in the event of vascular injury

CONCOMITANT ORGAN DYSFUNCTION

• Lung cancer: Respiratory reserves may be suboptimal • Eaton–Lambert signs may be present from oat cell carcinoma, leading to resistance to depolarizing agents and increased sensitivity to nondepolarizing muscle relaxants • Compression of vascular structures by a mass: Include the heart, pulmonary artery, or superior vena cava (SVC). SVC obstruction may lead to increased ICP

TREATMENT PREOPERATIVE PREPARATION Premedications

Anxiolysis may be considered if there is no evidence of airway obstruction. Special Concerns for Informed Consent

• Awake fiberoptic intubation may be planned when there is a risk for airway obstruction (mass is encroaching into the trachea) or potential for anterior mediastinal mass collapse. Discuss the indications and reasonable sedation goals. • Massive blood loss, requiring transfusion of blood products.

Antibiotics/Common Organisms

A third generation cephalosporin for skin organisms INTRAOPERATIVE CARE Choice of Anesthesia

General endotracheal anesthesia with neuromuscular blockade offers a more controlled environment, especially with surgical manipulation Monitors

• Standard monitors • Radial arterial line • Large bore peripheral IV (14–16G) • Arterial line and/or pulse oximeter should be placed on the right upper extremity in order to immediately recognize compression of the innominate artery by surgical manipulation.

Induction/Airway Management

• Awake fiberoptic intubation if there is an anticipated difficult airway or risk of airway obstruction with induction and muscle relaxant. This technique will allow for the maintenance of airway patency and spontaneous ventilation while securing the airway. • IV induction with muscle relaxant (short acting) if the patient has no signs or symptoms of airway compression or obstruction. • Mask induction to maintain spontaneous ventilation may also be used if there is concern about airway obstruction with muscle relaxant and no contraindications such as GERD.

Maintenance

• Volatile anesthetic or total intravenous anesthesia may be chosen. Volatile agents are chosen when spontaneous ventilation is desired and should be considered in patients with reactive airway disease (potent bronchodilators). • Muscle relaxants can aid with surgical manipulation and visualization as well as prevent coughing and venous engorgement in the chest. However, it should be avoided when attempting to keep the patient spontaneously ventilating. • Avoid nitrous oxide due to the potential for pneumothorax and pneumomediastinum.

Extubation/Emergence

• Plan for extubation in the operating room. • If the surgeon identifies potential damage to the recurrent laryngeal nerve, assess injury after extubation by having the patient vocalize the letter “e.”

FOLLOW-UP BED ACUITY

• Recovery room with discharge either to home or floor. • ICU if major vascular injury with resulting reconstruction or repair. • A chest radiograph is performed in all patients to evaluate for a pneumothorax.

ANALGESIA

• Parenteral opioids. • Ketorolac. • Local anesthetic can be injected at the skin incision by the surgeon.

COMPLICATIONS

• Vascular injury is more common at the lower right paratracheal node (4R) biopsy site. • Pneumothorax • Recurrent laryngeal nerve injury • Cerebral ischemia due to compression of the innominate artery (especially in those patients with pre-existing cerebral malperfusion)

REFERENCES

1. Lemaire A, et al. Nine-year single center experience with cervical mediastinoscopy: Complications and false negative rate. Ann Thorac Surg. 2006;82:1185–1190. 2. McCurdy MD, Philips PA, Marty AT, et al. Mediastinoscopy: Procedure of choice for diagnosis and determination of operability. Cardiovasc Dis. 1974;1(3):242–250. 3. Cho JH, Kim J, Choi YS. A comparative analysis of video-assisted mediastinoscopy and conventional mediastinoscopy. Ann Thorac Surg. 2011;92(3):1007–1011. 4. Bulut T, Brutel de la Riviere A. Mediastinoscopy as a therapeutic tool. Ann Thorac Surg. 2011;91(5):1616–1618. 5. Rami Porta R. Surgical exploration of the mediastinum by mediastinoscopy, parasternal mediastinoscopy and remediastinoscopy: Indications, technique and complications. Ann Ital Chir. 1999;70(6):867–872. 6. Fernandez A, Campos JR, Filomeno LT, Jatene FB. Mediastinoscopy: Technical aspects and current indications. Rev Hosp Clin Fac Med Sao Paulo. 1994:49(4):164–167. See Also (Topic, Algorithm, Electronic Media Element) • Anterior mediastinal mass • Superior vena cava syndrome • Recurrent laryngeal nerve

CLINICAL PEARLS

• Be prepared for complications including bleeding, pneumothorax, airway collapse. • Radial arterial line and/or pulse oximeter should be placed on the right upper extremity to immediately identify innominate artery compression. • Video-assisted mediastinoscopic lymph node biopsy may be associated with fewer complications than direct visualization. In addition, it may allow for examination and removal of more lymph nodes than conventional mediastinoscopy.

MEDICATION ERRORS

Ronnie J. Glavin, MB, ChB, MPhil, FRCA, FRCP (Glas)

BASICS DESCRIPTION

• The National Coordinating Council for Medication Errors Reporting and Prevention defines a medication error as any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient, or consumer. Such events may be related to professional practice, health care products, procedures, and systems, including: prescribing order communication; product labeling; packaging; nomenclature; compounding; dispensing; distribution; administration; education use. • This definition emphasizes the complexity of drug preparation and administration and the many different stages at which something can go wrong. • A more workable definition is provided by the Institute of Medicine – an adverse drug event is an injury caused by medical management rather than the underlying condition of the patient. • An adverse drug reaction is a response to a drug that is noxious and unintended and occurs at doses normally used for the prophylaxis, diagnosis, and therapy of disease or for the modification of physiological functions. EPIDEMIOLOGY Prevalence

• Ranges from 0.5 to 1 errors/near misses per 133 patients undergoing anesthesia (1,2)[C]. • In US hospitals, adverse medication events range from 2 to 6 per 100 admissions. Prevalence

The FDA (3)[C] estimates 3 billion prescriptions are prescribed annually with adverse events resulting in more than 4 million hospital visits and 117,000 hospitalizations annually. Morbidity

Medication errors in anesthesia may result in awareness, prolonged anesthesia, and a need for prolonged ventilation. Mortality

A UK retrospective study using data from a national voluntary reporting system reported an incidence of 15 fatal or severely harmful episodes in 1,120 medication errors (1.3%) but did not define severe harm. ETIOLOGY/RISK FACTORS Common errors include:

• Incorrect dose • Substitution (syringe swap or wrong drug drawn up into syringe) • Omission (not giving the drug when intended) • Repetition

PHYSIOLOGY/PATHOPHYSIOLOGY

• Medication errors can usually be divided into two main categories: Active failures and latent conditions. • Active failures – Slips (failures of attention), for example, picking up the wrong syringe. – Lapses (failure of memory), for example, being interrupted while programming an infusion pump and forgetting to complete the program may result in that infusion not being delivered when expected or in the dose expected. – Rule-based mistakes in which the wrong rule may be invoked. An example includes emergency care when the use of amiodarone or magnesium as part of the management of acute cardiac events may be associated with wrong dilutions or incorrect rates of administration. The written material accompanying the packaging is not always easily read during crises. – Knowledge-based mistakes in which the wrong drug is prescribed or administered, but the person believes it to be the appropriate choice for that clinical context. – Violations in which the person administering or prescribing the drug knows what the correct action should be, but chooses to ignore it. For example, choosing to use an amount of local anesthetic drug that exceeds the recommended toxicity thresholds. • Latent conditions refer to components in the system that do not normally contribute to harm but when the appropriate circumstances apply, they will emerge. For example, if the electronic dispensing facility in a hospital pharmacy broke down and the doctors could not access further supplies of emergency drug, then an adverse outcome for the patient could result. These can contribute to errors or mistakes taking place. Luckily, many errors do not result in serious or life-threatening episodes because some defensive mechanisms are present. • The list of active failures highlights the importance of effective cognitive processes: Attention, memory, recall of knowledge. Circumstances that interfere with these are more likely to result in slips, lapses and mistakes and also errors of judgment, which in turn may influence the performance. Interruptions while preparing drugs may result in the wrong drug being drawn up into the syringe. Fatigue, hunger, thirst, cold or hot environments may all contribute to a reduction in attention or the effectiveness of working memory. Busy periods when many demands are placed on the anesthesia provider and unexpected emergencies where the solution is not obvious will also place a burden on the cognitive powers of the anesthesia provider, increasing the likelihood of errors and mistakes.

PREVENTATIVE MEASURES

• General measures – Creating a working environment where unnecessary distractions are discouraged and where extra vigilance is encouraged (for example cross checking complex programming of infusion pumps or calculations of infusions) during conditions of fatigue or stress.

Recognizing the presence of hunger or thirst and taking pre-emptive measures to prevent them from getting worse. Recognizing one’s own state of health, including the use of any medication. – A helpful self-checklist used in aviation is ‘I’M SAFE’, which may also be used to determine safety when caring for patients. Illness Medication Stress Alcohol Fatigue Emotion • Specific measures: Jensen (4)[A] described a list of twelve such actions and linked them to the strength of evidence for their effectiveness. These are, listed by the strength of evidence, as follows: – Strongly recommended The label on any drug or ampule or syringe should be carefully read before a drug is drawn up or injected. Legibility and contents of labels on ampules and syringes should be optimized according to agreed standards. Syringes should be labeled (always or almost always). Formal organization of drug drawers and workspaces should be used. – Recommended Labels should be checked specifically with a second person or device before a drug is drawn up or administered. Errors in IV drug administration during anesthesia should be reported and reviewed. Management of the drug inventory should focus on minimizing the risk of drug error. Similar packaging and presentation of drugs should be avoided where possible. – Possibly recommended Drugs should be presented in prefilled syringes rather than ampules. Drugs should be drawn up and administered by the anesthetist who will administer them. Color coding by class of drug according to an agreed national or international standard should be used. – Unclear Coding by syringe position or by the needle on the syringe should be used.

PREOPERATIVE ASSESSMENT • This will depend on the effects of the drug. A useful classification system gives six categories of drug reaction. These are as follows: – Augmented (dose-related) – Bizarre (non-dose-related) – Chronic (dose-related) – Delayed (time-related)

– End of use (withdrawal) – Failure (unexpected failure of therapy) – Most medication errors seen by anesthesia providers will fall into the first two categories of the above list. • It is very important to remember that medication errors affecting the patient may be due to the actions of other health care workers or even the patient and not confined to the actions of the individual anesthesia provider. For example, a patient may have been advised to omit a regular antihypertensive drug before attending surgery under anesthesia. An even more severe case would be one in which a patient with an acute medical condition had been charted as having been given a drug but had not actually received that drug. An anesthesia provider anticipating some therapeutic benefit may then be faced with an adverse outcome, for example, a patient with heartburn who had not received a scheduled dose of protein pump inhibitor or H2 blocker could be at greater risk of adverse reaction to aspiration of gastric contents. • Many of the adverse outcomes in the prospective studies were related to actions of anesthetic drugs: Prolonged anesthesia or need for prolonged ventilation. A high index of suspicion should be maintained if a patient appears to be unduly sensitive or resistant to a commonly administered anesthetic drug.

DIFFERENTIAL DIAGNOSIS

There are many ways in which a medication error may present but in the context of anesthesiology, most will present acutely and so are more likely to fall into the augmented or bizarre categories of drug reaction.

TREATMENT • Treatment will be a combination of specific and supportive. The most important component is awareness on the part of the anesthesia provider that an abnormal response by the patient may be due to a reaction to a medication error. • As an example, if a spontaneously breathing patient demonstrated signs of respiratory depression, then appropriate supportive therapy should begin at once – conversion to positive pressure ventilation and so on. A quick review of the drug ampules used may confirm that higher concentration of opioid drug than intended was prepared and administered. The specific treatment would be consideration of the use of an antagonist such as naloxone.

FOLLOW-UP The importance of the use of the generic error system is that it provides a framework that allows the anesthesia provider to structure a critical incident report. The inclusion of any latent conditions is particularly important to help identify and eliminate these and so reduce their possible future contribution to potential adverse outcome (5)[C] .

REFERENCES

1. Webster CS, Merry AF, Larsson L, et al. The frequency and nature of drug administration error during anaesthesia. Anaesth Intensive Care. 2001; 29(5):494–500.

2. Llewellyn RL, Gordon PC, Wheatcroft D, et al. Drug administration errors: A prospective study survey from three South African teaching hospitals. Anaesth Intensive Care. 2009;37(1):93–98.

3. U.S. Department of Health and Human Services Food and Drug Administration. FDAs Safe Use Initiative: Collaborating to reduce preventable harm from medications. 2009 – see website below (last accessed 27th February, 2011)

4. Jensen LS, Merry AF, Webster CS, et al. Evidence-based strategies for preventing drug errors during anaesthesia. Anaesthesia. 2004; 59(5):493–504. 5. Glavin RJ. Drug errors: Consequences, mechanisms, and avoidance. Br J Anaesth. 2010;105(1):76–82.

ADDITIONAL READING

• FDA Safe drug initiative – variety of documents and workshops available at http://www.fda.gov/Drugs/DrugSafety/ucm187806.htm • Dornan T, Ashcroft D, Heathfield H, et al. An in depth investigation into causes of prescribing errors by foundation trainees in relation to their medical education. EQUIP Study. General Medical Council, 2009. Available from http://www.gmcuk.org/about/research/research_commissioned.asp (accessed 27th February 2011).

CODES ICD9 • 960–979—poisoning by drugs, medicinals and biological substances • 968.0–968.9—poisoning by other central nervous depressants and anesthetics

CLINICAL PEARLS

• Medication errors are common and although the majority of them result in very little patient harm, the potential for patient death or severe harm is always present. • If an abnormal patient response occurs in response to an anesthetic intervention, think “Could this be a medication error?” • Medication errors are more likely during circumstances in which the cognitive processes of the anesthesia provider are under pressure.

METABOLIC ACIDOSIS Kanishka Monis, MD Poovendran Saththasivam, MD

BASICS DESCRIPTION

• Metabolic acidosis is defined as a plasma pH <7.35 that results from either an increase in nonvolatile acid production or loss of bicarbonate ions. It can: – Be acute, lasting minutes to days (common); or chronic, lasting weeks to months (less common). – Results when the body’s multiple buffering and compensatory mechanisms are exhausted. • Metabolic acidosis is divided into a normal or increased anion gap and is useful in establishing a differential diagnosis. Anion gap is defined as the unmeasured anions present in the plasma; it does not imply that anions are missing, but only that they are not directly measured. It is calculated as follows: – Anion gap = [Na+] − ([Cl-] + [HCO3-]).

– A normal anion gap is 6–10 mmol/L and is attributed to serum albumin, phosphates, and sulfates. – Perioperatively, the base excess is more commonly utilized in determining the extent of increased acid load. This is because metabolic acidosis is most commonly the result of anaerobic metabolism (lactic acidosis).

EPIDEMIOLOGY Incidence

Acute metabolic acidosis is estimated to affect ∼64% of ICU patients (1). Prevalence

Chronic metabolic acidosis has an increased prevalence in patients with chronic kidney disease. Morbidity

Primarily related to the underlying disease Mortality

Primarily related to the underlying disease ETIOLOGY/RISK FACTORS

• Increased anion gap metabolic acidosis results from increased nonvolatile acid (2,3). – Lactic acidosis – Uremia – Ketoacidosis

– Intoxication: Methanol, ethylene glycol, salicylates, paraldehyde • Normal anion gap metabolic acidosis results from the loss of bicarbonate: – Diarrhea – Chronic kidney disease – Adrenal insufficiency – Drugs: Spironolactone, prostaglandin inhibitors, triamterene, amiloride, cyclosporine – Hyperkalemic distal renal tubular acidosis (RTA) – Type I and Type II (Gordon’s syndrome) pseudoaldosteronism

PHYSIOLOGY/PATHOPHYSIOLOGY

• Normal acid production is 1 mmol/kg/day in adults and 1–3 mmol/kg/day in infants and children. • The hydrogen ion concentration is tightly regulated in the body to maintain a physiologic [H+] of 40 mEq/L. There are 3 key mechanisms: – Intracellular and extracellular buffering systems are the first-line mechanisms to remove excessive [H+]. Carbonic acid/bicarbonate system: [H+] + [HCO3−] ←→ H2CO3 carbonic anhydrase H2O + CO2. When the [H+] increases, the [HCO3−] declines as more H2CO3 forms. Carbonic anhydrase will convert H2CO3 to CO2 and H2O.

Phosphate: [H2PO4−] [H+] + [HPO44−]. The high intracellular concentration makes it

an important intracellular buffer. Hemoglobin Plasma proteins – Alveolar ventilation and elimination of carbon dioxide (CO2)

Increases in [H+] stimulate chemoreceptors in the carotid body to increase minute ventilation and exhalation of CO2. Winter’s formula aids with identifying the presence of a mixed respiratory disorder: PaCO2 = (1.5 × [HCO3-]) + 8 ± 2. When the calculated and measured PaCO2

correspond, it suggests that the metabolic acidosis is an isolated disorder. If the measured PaCO2 is greater than the calculated PaCO2, a primary respiratory acidosis is

also present; whereas, if the measured PaCO2 is lower than the calculated PaCO2, a

primary respiratory alkalosis is also present. – Renal compensation: Reabsorption and secretion. Filtered HCO3− is converted to CO2 in the lumen of the renal tubule; it then diffuses into proximal tubule cells and is subsequently reconverted to HCO3− and returned to the systemic circulation. Thus, for each HCO3− that is

reabsorbed, an H+ is secreted into the urine by the renal tubular cell. • Effects on organ systems: – Cardiovascular Impaired contractility of the myocardium

Increased pulmonary vascular resistance Decreased systemic vascular resistance – Respiratory Hyperventilation (compensatory mechanism) Shift of oxygen dissociation curve to the right Decreased 2,3-Diphosphoglycerate (DPG) in red cells leads to a decrease in hemoglobin’s affinity to oxygen. There is a “left-shift" of the oxyhemoglobin curve. – Bone Chronic acidosis, as is seen with renal disease, can result in increased mobilization of calcium from bone secondary to cellular effects on osteoclasts and osteoblasts and impaired bone matrix mineralization.

PREVENTATIVE MEASURES

• Close monitoring of blood glucose levels in diabetics to prevent ketoacidosis. • Lactic acidosis results from tissue hypoxia (anaerobic metabolism) that is due to impaired perfusion or oxygen delivery – Maintain adequate volume in burn injuries, trauma, hemorrhage, diarrhea, bowel prep, third spacing – Maintain adequate perfusion with inotropes and vasopressors – Maintain adequate blood oxygen content via increasing the inspired oxygen fraction and possibly transfusing blood, if appropriate.

DIAGNOSIS • Symptoms are non-specific in the awake patient: – Chest pain – Palpitations – Altered mental status – Nausea and vomiting – Abdominal pain – Decreased visual acuity – Decreased appetite – Weight loss – Muscle weakness • Signs: Kussmaul respirations, tachypnea, cranial nerve damage (ethylene glycol poisoning). • Arterial blood gas measurements provide values for pH, HCO3−, PaCO2, and base excess and are assessed in context with one another. – pH <7.35 – [HCO3−] <24 mmol/L. Decreased from titration of nonvolatile anions or loss. – PaCO2: Assess for respiratory compensation or concurrent acidosis.

– Base excess: More frequently utilized than the anion gap in the perioperative period; this is because metabolic acidosis is often the result of lactic acidosis secondary to anaerobic metabolism. Aids with determining the extent of the increased acid load, as opposed to aiding in the differential diagnosis.

• Anion gap (AG) calculation aids with narrowing the diagnosis: AG = [Na+] − ([Cl-] + [HCO3-]). As mentioned above (1):

– Increased AG signifies an accumulation of endogenous or exogenous acids. – Normal or non-anion gap metabolic acidosis reflects the loss of HCO3− anions from the

kidneys or GI tract, the inability of the kidneys to excrete excess [H+], or overzealous fluid resuscitation with normal saline (hyperchloremic metabolic acidosis). • Urinary pH: Normally, the urine pH is less than 5. In patients with metabolic acidosis, urine pH becomes more acidic as the kidneys attempt to excrete the acid load. • Plasma glucose: The measurement is necessary to rule out diabetic ketoacidosis, along with urine ketones and glucose. • Hyperkalemia: Acidosis leads to intracellular shifting of hydrogen ions in exchange for potassium. The EKG may reveal peaked T waves, widening of the QRS complex, and reduction in the size of the P wave.

DIFFERENTIAL DIAGNOSIS • Respiratory acidosis: – Low pH – Increased PaCO2 – Low [HCO3−]

• Mixed metabolic and respiratory acidosis: Use Winter’s formula as mentioned before.

TREATMENT • Diabetic ketoacidosis: Fluid and electrolyte replacement and insulin therapy, as well as inciting cause (e.g., infection, myocardial infarction). • Uremia: Dialysis, hemofiltration and renal replacement therapy. • Lactic acidosis: Identify and treat the underlying cause (hypovolemia, hypoxia, hypoperfusion). • Sodium bicarbonate administration: In the acidotic patient, inotropes and vasopressors may have decreased efficacy and hinder therapy aimed at the underlying cause. – NaHCO3 dissociates into a sodium and bicarbonate ion. The bicarbonate ion can bind with

hydrogen ion to form H2CO3 which can be converted via carbonic anhydrase to water and

carbon dioxide. CO2 can be exhaled via the pulmonary system.

– The bicarbonate deficit can be calculated as follows: ([HCO3-]desired − [HCO3-]measured) ×

0.6 × body weight in kg). Bicarbonate levels should not be corrected >12 mmol/L in the initial correction to prevent over treatment. – However, its use remains controversial and has not been shown to improve the outcome, even in patients in cardiopulmonary arrest. In addition, hyperosmolarity and hypernatremia can have deleterious effects. An inability to increase minute ventilation can result in a respiratory acidosis.

REFERENCES

1. Maciel AT, Park M. Differences in acid–base behavior between intensive care unit survivors and nonsurvivors using both a physicochemical and a standard base excess approach: A prospective, observational study. J Crit Care. 2009;24(4):477–483. 2. Morris CG, Low J. Metabolic acidosis in the critically ill: Part 2. Causes and treatment. Anaesthesia. 2008;63(4):396–411.

3. Morris CG, Low J. Metabolic acidosis in the critically ill: Part 1. Classification and pathophysiology. Anaesthesia. 2008;63(3):294–301. See Also (Topic, Algorithm, Electronic Media Element) • ACLS anesthetic management. • Lactic acidosis • Diabetic ketoacidosis • Anion gap • Propofol infusion syndrome

CODES ICD9 276.2 Acidosis ICD10 E87.2 Acidosis

CLINICAL PEARLS

• Acidosis decreases protein binding of local anesthetics; therefore increasing the free fraction of the drug and its risk of systemic toxicity. • Propofol infusion syndrome should be suspected when metabolic acidosis develops in patients on a propofol infusion, combined with rhabdomyolysis and cardiac failure.

METABOLIC ALKALOSIS Kanishka Monis, MD Michael Grover, MD

BASICS DESCRIPTION

• Metabolic alkalosis is a pathophysiologic state of high plasma pH (>7.45) that can be caused by the: – Accumulation of base. – Loss of acid. – Loss of fluid containing chloride ion than bicarbonate from the extracellular space (1). • It may be classified as either: – Acute versus chronic. – With or without pulmonary compensation: The lungs attempt to blunt the pH change by decreasing exhalation of carbon dioxide; however, it cannot completely restore homeostasis. – Chloride depletion, potassium depletion, volume contraction, or iatrogenic. The literature, however, discusses several other methods to classify metabolic alkalosis based upon the etiology (e.g., organ dependent) (2). • Because pH homeostasis is essential for the proper function of enzymes and protein, organ dysfunction (e.g., impaired inotropy, decreased cerebral blood flow) and impaired drug clearance may be seen (3). EPIDEMIOLOGY Mortality

• Medical and surgical inpatients with an arterial blood pH of 7.55 have been shown to have a 45% mortality (2). • Medical and surgical inpatients with an arterial blood pH of 7.65 have been shown to have an 80% mortality (2).

ETIOLOGY/RISK FACTORS

• Chloride depletion (2,4): – Gastric losses: Vomiting, nasogastric suctioning, bulimia, or pyloric stenosis – Diarrheal states: Villous adenoma, congenital chloridorrhea, inflammatory bowel disease – Use of chloruretic diuretics: Chlorothiazide, bumetanide – Cystic fibrosis • Potassium depletion (5) • Volume depletion: (Often results in, or is secondary to, chloride or potassium depletion). This is also referred to as “contraction alkalosis” in the literature (2). • Iatrogenic: Sodium bicarbonate administration.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Metabolic alkalosis can be classified by the: – Underlying pathophysiology: Chloride or potassium depletion, volume contraction, mineralocorticoid excess – Primary organ system involved (2) • Hypokalemia can cause or maintain metabolic alkalosis due to: – Intracellular shifting of hydrogen ions. – Stimulation of H+/K+ ATPase receptors at the collecting ducts. To re-establish normal potassium levels, the receptor increases potassium ion reabsorption while secreting hydrogen ion into the urine. – An increase in renal ammonia production with resultant net acid excretion as NH4+; the exact mechanism is unknown (2,6). • Chloride depletion enhances absorption and impairs excretion of bicarbonate in the kidneys. – Low levels are sensed by the macula densa and stimulate the renin–angiotensin– aldosterone system (RAAS). The RAAS functions to increase volume, retain sodium, and excrete potassium. At the level of the collecting duct, sodium is retained at the cost of hydrogen secretion into the urine. – Impairs the Cl−/HCO3− exchanger at the level of the collecting duct (2).

• Decreased volume – Decreases in glomerular filtration rate (GFR) will decrease the filtered load of bicarbonate at the glomerulus and hence excretion in urine (2). – Stimulates the renin–angiotensin–aldosterone system. At the level of the collecting duct, sodium is retained at the cost of hydrogen secretion into the urine. The maintenance of volume supersedes pH homeostasis (2). • Gastrointestinal – Gastric fluid contains 60–140 mM HCl. It can be quickly depleted with vomiting or suctioning. In addition, extracellular fluid (ECF) volume contraction, as well as sodium and potassium loss can stimulate renin and aldosterone production with renal compensation (4). – Villous adenomas secrete chloride rather than potassium and bicarbonate (4). • Skin: Cystic fibrosis is a genetic defect that causes an abnormal chloride channel protein and impaired cAMP-regulated chloride transport across epithelial cells leading to metabolic alkalosis by chloride depletion (2). • Compensation: Increases in pH depress central and peripheral receptors with resultant hypoventilation/hypercapnia. The ability to compensate, however, is limited due to: – Hypoxia from rising alveolar carbon dioxide partial pressures can stimulation chemoreceptors and result in hyperventilation. – Mechanical ventilation: Unless recognized and adjusted for, ventilator settings can result in a “relative” hyperventilatory state. – Pain in patients who are breathing spontaneously.

DIAGNOSIS

• The presence of symptoms such as cardiac arrhythmias, confusion, neuromuscular irritability or weakness, and hypoventilation (hypoxia and increased PaCO2) may suggest a

metabolic alkalosis (2). • Arterial blood gases: – Elevated pH – Increased bicarbonate concentration – Differentiate between acute and chronic processes – Identify the presence of a mixed disorder. The expected PaCO2 = 0.7[HCO3−] + 20, range ±5; the large range is the result of factors that can impair hypoventilation (see above). When the expected PaCO2 is increased or decreased, consider the possibility of a

concomitant respiratory acidosis or alkalosis. • The measurement of urinary chloride and potassium can aid with narrowing the diagnosis (however, this is not routinely performed in the perioperative setting) (2,4). – Urinary chloride <10 mEq/L Chloride depletion alkalosis Gastric losses Cystic fibrosis Colonic villous adenoma Dietary chloride deprivation – Urinary potassium concentration >30 mEq/L Renal potassium wasting Diuretics High circulating aldosterone – Urinary potassium <20 mEq/L Extrarenal potassium loss

DIFFERENTIAL DIAGNOSIS

Metabolic alkalosis is a unique disorder that is always a sign of some other underlying disease; thus, the etiology is, in itself, the differential diagnosis.

TREATMENT • Treatment should be aimed at the underlying etiology. Replacement of chloride, potassium, and volume may also be indicated, as appropriate. • Chloride responsive alkalosis (2) – Volume depleted/contracted: Administer normal saline ([Cl−] = 154 mEq/L). When severely dehydrated, reabsorption of chloride takes precedence over acid reabsorption (also known as paradoxical aciduria). The base is eventually excreted by the kidneys as volume is replenished and chloride becomes available. – Normovolemic patients: The chloride deficit can be calculated by: ([0.2 × body weight (kg)] × [difference between desired and current plasma chloride (mEq/L)]). The deficit can be replaced intravenously; ensure that chronic electrolyte disturbances are not rapidly corrected.

– Volume overload: In patients with congestive heart failure, chloride should be repleted with KCl, instead of NaCl. If hyperkalemia exists, then intravenous HCl may be indicated. – Potassium concentration must be monitored closely during the course of treatment and repleted as necessary. Hypokalemia is a common occurrence with rehydration. – Acetazolamide can be given to patients with normal renal function or when normal saline infusion is not effective; it promotes diuresis of NaHCO3 by the inhibition of carbonic

anhydrase. • Chloride-resistant alkalosis/hypokalemia (2): – Oral or intravenous KCl: Mild to moderate hypokalemia: oral KCl 40–60 mEq 4–5 times per day. Severe or life-threatening hypokalemia up to 40 mEq per hour IV potassium may be used (central line administration). Patients should have continuous EKG monitoring when high rates of IV KCl are used.

REFERENCES

1. Medarov BI. Milk-alkali syndrome. Mayo Clin Proc. 2009;84(3):261–267. 2. Galla JH. Metabolic alkalosis. J Am Soc Nephrol. 2000;11(2):369–375. 3. Anderson LE, Henrich WL. Alkalemia-associated morbidity and mortality in medical and surgical patients. South Med J. 1987;80(6):729–733. 4. Gennari FJ, Weise WJ. Acid–base disturbances in gastrointestinal disease. Clin J Am Soc Nephrol. 2008;3(6):1861–1868. 5. Assadi F. Diagnosis of hypokalemia: A problem-solving approach to clinical cases. Iran J Kidney Dis. 2008;2(3):115–122. 6. Weinstein AM. A mathematical model of distal nephron acidification: Diuretic effects. Am J Physiol Renal Physiol. 2008;295(5):F1353–1364. See Also (Topic, Algorithm, Electronic Media Element) • Respiratory alkalosis • Hypokalemia • Cystic fibrosis

CODES ICD9 276.3 Alkalosis ICD10 E87.3 Alkalosis

CLINICAL PEARLS

• Perioperative metabolic alkalosis can be seen with:

– In patients with chronic respiratory failure (respiratory acidosis), a compensatory metabolic alkalosis may develop. – Administration of hypernatremic solutions (e.g., normal saline) results in an increased strong ion deficit due to sodium gain. Sodium is buffered by bicarbonate. • Metabolic alkalosis can result in: – Electrolyte disturbances leading to arrhythmias, cardiovascular collapse, altered mental status, and delayed emergence. – pH abnormalities can decrease inotropy and increase cerebral blood flow. – Increased affinity of oxygen to hemoglobin, shifting the oxygen–hemoglobin dissociation curve to the left. – Altered efficacy and clearance of medications. – Increased mortality.

METHEMOGLOBINEMIA David P. Frey, DO Adam Thaler, DO

BASICS DESCRIPTION

• Methemoglobin (MetHb) was first described by Felix Hoppe-Seyler in 1864. • MetHb is a potentially lethal accumulation of oxidized hemoglobin. Although it is usually acquired, it can also be congenital. EPIDEMIOLOGY Incidence

• Dapsone (used to treat leprosy, or Pneumocystis pneumonia) accounts for 42% of acquired cases (1). • Benzocaine spray accounts for the most severe cases (1). Prevalence

50% of cases involve infants and the elderly, with infants <4 months being particularly susceptible (2).

Mortality

Death occurs when methemoglobin fractions approach 70%. ETIOLOGY/RISK FACTORS

• Exposure to an oxidizing agent is the most common cause of MetHb (3). – Examples of oxidizing agents: Benzocaine, lidocaine, prilocaine, acetaminophen, methylene blue (high dose), metoclopramide, and nitrates; also aniline, dapsone, celecoxib, chloroquine, cyclophosphamide, ifosfamide, methanol, phenazopyridine, phenytoin, primaquine, riluzole, trimethoprim–sulfamethoxazole. – Other exogenous oxidizing agents are found in teething gels, automobile exhaust, inhalants, industrial chemicals, smoke, and pesticides. • Well water and foods containing nitrates can be converted to nitrites (powerful oxidizers) by intestinal flora (4). • States of high oxidative stress including systemic infection and cancer (3). • Anemia (including mild degrees): MetHb is more likely to progress to symptoms when there is a lower hemoglobin reserve. • Acidosis: Endogenous reducing enzymes are less efficient at a low pH (4). • Idiopathic MetHb is commonly seen among infants <4 months old (4). • Genetic mutation is a rare cause of MetHb. Although usually benign, these patients are at increased risk of developing acute toxicity when exposed to oxidizers or oxidative states (4). • Other than the risk factors described herein, it is unknown why some people develop MetHb

while others do not.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Oxidative toxicity involves the “redox” reaction, or loss of electrons from a substrate; whereas reduction involves the transfer (gain) of electrons to a substrate. • Hemoglobin is composed of four heme groups, each with one atom of iron. The iron atom binds oxygen only in the reduced ferrous (Fe2+) state. Thus, when oxidation occurs (Fe2+ to Fe3+), a ferric heme state is created, known as methemoglobin, that does not bind and

transport oxygen to tissues. • RBC’s are uniquely susceptible to oxidation and as such, MetHb typically presents before oxidative injury in other tissues. RBCs: – Carry O2, and hence are constantly exposed to oxygen free radicals.

– Lack a nucleus and cannot synthesize new proteins; thus “older” cells are more prone to oxidative injury. – Lack mitochondria. They are less efficient at generating the cofactors and energy needed for reducing enzymes. • Normally, methemoglobin is quickly reduced (gains electrons) back to hemoglobin by cytochrome-b5 reductase (b5R); it is responsible for 99% of daily methemoglobin reduction. This keeps methemoglobin levels at around 1% in healthy individuals. • Methemoglobin is incapable of binding O2, and additionally, the Fe3+ heme creates an allosteric change that decreases the O2 unloading from any remaining Fe2+ heme groups.

Thus, it produces a combined: – Decrease in O2 carrying capacity; oxyhemoglobin becomes non-oxygen carrying methemoglobin. – Decrease in peripheral O2 delivery (impaired unloading); seen as a left-shift of the oxygen-

dissociation curve. – These abnormalities result in functional anemia and tissue hypoxia. • MetHb occurs when there is: – Increased methemoglobin production. – Decreased reduction capacity. – Thus, toxicity and symptoms depend on the methemoglobin level and any concomitant conditions that impair the ability to deliver O2 to the tissues. • Methemoglobin can also covalently bind sulfur to form sulfhemoglobin. Endogenous glutathione can serve as the sulfur donor and many drugs capable of producing MetHb can also produce sulfhemoglobinemia, which will affect treatment (4).

PREVENTATIVE MEASURES

• Re-exposure, high concentrations (>20%), and liberal use of benzocaine should be avoided. • Identify those individuals at high risk and make methylene blue (MB) and blood available for the procedure.

DIAGNOSIS

• Cyanosis is the first sign. – Develops with 1.5 g/dL of methemoglobin (∼15% total hemoglobin) due to its spectrographic properties as compared to deoxyhemoglobin that requires 5 g/dL – Difficult to detect in dark skinned patients – Maintain a high index of suspicion when cyanosis is refractory to O2 supplementation, and especially if it develops 20–60 minutes (up to 2 hours) after benzocaine, prilocaine, or lidocaine administration • Severity of symptoms is dependent on the level of methemoglobin. MetHb as a % of total hemoglobin: – <1.5% – asymptomatic – 10–20% – cyanosis – 30–40% – headache, fatigue, weakness, tachycardia, tachypnea, chest pain, and dizziness – 40–50% – dyspnea, confusion, and lethargy – 50–60% – acidosis, arrhythmias, hypoxia, seizures, coma, bradycardia, and ventricular dysrhythmias – >70% – death • Concomitant conditions: Anemia, acidosis, respiratory compromise, and cardiac disease may make patients more symptomatic for a given methemoglobin level. • Oxidant-induced hemolysis can accompany MetHb. • Pulse oximeters measure two wavelengths of light: 660 nm (red, oxyhemoglobin) and 940 nm (infrared, deoxyhemoglobin). Methemoglobin absorbs equal amounts of these wavelengths; a ratio of pulsatile and nonpulsatile absorbances equal to 1 corresponds to a hemoglobin saturation of 85%. Thus, regardless of the actual oxygen saturation, MetHb will read at 85% oxygen saturation on pulse oximeter. • Co-oximeters detect multiple wavelengths of light, and can measure the concentration of different forms of hemoglobin including reduced hemoglobin, oxyhemoglobin, carboxyhemoglobin, and methemoglobin. Measurements are accurate and available in <2 minutes. – Methemoglobin levels rise with storage time – Both sulfhemoglobin and MB have similar absorbencies and will be reported as methemoglobin • Arterial line: Placement allows for frequent arterial blood gas (ABG) measurements (lactic acidosis), beat-to-beat pressure regulation, and direct measurement of methemoglobin levels. Because PaO2 refers to dissolved gas, it will reflect true partial pressure values; however, the SpO2% calculation assumes normal hemoglobin oxygen binding characteristics and will yield a false value. Thus, the SaO2% should be directly measured by the lab.

• Arterial blood appearance – High concentrations of methemoglobin appear chocolate brown. – Deoxyhemoglobin appears dark red and upon exposure to atmospheric O2 will turn bright red. In contrast, methemoglobin will not change color over time, as it is unable to bind to oxygen. – Sulfhemoglobin also appears chocolate brown. • EKG: Presence of myocardial ischemia indicates decreased O2 delivery to other tissues.

• Potassium cyanide (Drabkin’s reagent) test. – Distinguishes between sulfhemoglobin and methemoglobin. – Methemoglobin will react to the addition of potassium cyanide and turns bright red. – Sulfhemoglobin is inert and will remain chocolate brown.

DIFFERENTIAL DIAGNOSIS

• Respiratory/cardiac compromise • Sulfhemoglobinemia • G6PD deficiency • Nicotinamide adenine dinucleotide phosphate (NADPH)-methemoglobin reductase deficiency • Congenital MetHb

TREATMENT • MetHb toxicity can be rapidly lethal but with prompt recognition and early initiation of treatment, outcomes are good. • Any oxidizing agents should be sought and discontinued. • Supportive care – Administer 100% oxygen – Maintain airway – Hemodynamic support • Methylene blue (MB): NADPH-methemoglobin reductase is a generalized reductase found in the body and has a high affinity for MB dye. If NADPH is available, it will reduce MB, which in turn reduces methemoglobin back to hemoglobin. – Treatment is indicated at approximately 20% MetHb in symptomatic patients, 30% MetHb in asymptomatic patients, and 10–30% MetHb in patients with concurrent problems that compromise O2 delivery. – The dose of 1% solution is 1–2 mg/kg or 0.1–0.2 mL/kg over 3–5 minutes intravenously, followed by 15–30 mL normal saline flush. If symptoms persist after 20 minutes, another dose of 1 mg/kg can be given 30–60 minutes after the initial dose. Do not exceed a total of 7 mg/kg because at these doses, MB can cause MetHb. – Ineffective in the following scenarios: G6PD deficiency: NADPH is largely generated by glucose-6-phosphate dehydrogenase (G6PD). MB may also induce oxidant injury or hemolysis NADPH-methemoglobin reductase deficiency Sulfhemoglobin emia • Secondary options if failure to respond to standard treatment or methemoglobin levels exceed 50%: – Hyperbaric oxygen administration – Exchange transfusion • Dextrose solutions catabolize glucose via glycolysis and replenish NADH and NADPH, which are both necessary cofactors for the reduction of methemoglobin.

FOLLOW-UP • An ABG should be obtained to confirm the absence of acidosis and no increase in methemoglobin. • Therapeutic MB can cause a false elevation in methemoglobin levels due to the similar absorbance spectrum. Confirmation should be performed by using the specific Evelyn– Malloy method which involves adding cyanide and ferricyanide reagents. • Some drugs like dapsone and aniline have been reported to produce a rebound MetHb 4–12 hours after successful MB therapy because their metabolites are oxidizers. • Oxidative hemolysis can follow MetHb 12–24 hours after first exposure to the etiologic agent. • The future use of oxidizing agents should be avoided in these patients.

REFERENCES

1. Hamilton RJ. Acquired methemoglobinemia: A retrospective series of 138 cases at 2 teaching hospitals. Ann Emerg Med. 2005;46(5):477–478. 2. So T, et al. Topical benzocaine-induced methemoglobinemia in the pediatric population. J Pediatr Health Care. 2008;22(6):335–339. 3. Kane GC, et al. Benzocaine-induced methemoglobinemia based on the Mayo Clinic Experience from 28,478 transesophageal echocardiograms. Arch Intern Med. 2007;167(18): 1977–1982. 4. Wright RO, et al. Methemoglobinemia: Etiology, pharmacology, and clinical management. Ann Emerg Med. 1999;34(5):646–656. See Also (Topic, Algorithm, Electronic Media Element) • Pulse oximeter • Cyanide poisoning • Hyperbaric oxygen • Anaerobic metabolism • Hemoglobin

CODES ICD9 289.7 Methemoglobinemia ICD10 D74.9 Methemoglobinemia, unspecified

CLINICAL PEARLS

• Dapsone is the leading cause of drug acquired cases; whereas, benzocaine spray accounts for the most severely acute elevations.

• MetHb produces a combined decrease in O2 carrying capacity and peripheral O2 delivery.

• The same drugs that cause hemolysis in G6PD deficiency can cause MetHb. • Methemoglobin binds cyanide to form the nontoxic cyanomethemoglobin and is part of the treatment for cyanide poisoning. • Recognition and treatment with IV MB is imperative to save lives. Failure to respond to MB include: – Incorrect diagnosis (e.g., sulfhemoglobinemia) – Ongoing toxin absorption – G6PD deficiency – Congenital MetHb – NADPH-dependent methemoglobin reductase deficiency – Unique toxin • Pulse oximetry – Measures light absorbance at the wavelengths 660 and 940 nm which is the absorbance of oxy- and deoxygenated blood, respectively. SpO2 is calculated from this ratio – Methemoglobin is absorbed at both of these wavelengths and will give a false value – Significant methemoglobin will only be detected as mild to moderate O2 desaturation

MINIMUM ALVEOLAR CONCENTRATION (MAC) Jeffrey W. Lim, MD, PhD Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• The “minimum alveolar concentration,” or MAC, is the alveolar fraction/concentration of volatile anesthetic that is able to prevent 50% of subjects from moving in response to surgical stimuli (1). • The concept of MAC is utilized intraoperatively as an index of: – Depth – Induction – Recovery – As well as for studies to standardize doses for different agents and to measure and assess potency (1)

PHYSIOLOGY PRINCIPLES

• Volatile agents are: – Halogenated hydrocarbons that are hydrophobic – Used perioperatively for the induction and maintenance of general anesthesia. Other uses include bronchodilation during status asthmaticus – Stored as liquids at room temperature and vaporized for anesthetic delivery via the inhaled route – Able to provide loss of consciousness, amnesia, and immobility • Pharmacodynamics: Their mechanism is unknown, but believed to act on multiple areas (unlike intravenous medications that act on a single receptor) and disrupt electrical transmission (via proteins, membrane receptors, intracellular systems) and synapses at a lower concentration than axonal synapses (2). • Pharmacokinetics – The concentration of gases are measured as partial pressures; they are denoted by Plocation (Pbrain, PA, Pa, etc; units are mmHg). However, volatile agents are denoted as fractions;

Flocation (Fbrain, FA, Fa, etc; units are %). For example, sevoflurane 2% indicates that the

agent comprises 2% of the total inspired gas. – Tissue groups: The vessel-rich group (brain, heart, liver, kidney, and endocrine organs) receives significant blood flow and concentrations quickly rise; however, they also have a small overall capacity. The muscles, fat, and the vessel-poor group (bone, ligaments, teeth, hair, and cartilage) receive less blood flow (hence volatile agent delivery) and concentrations take longer to rise; however, they have a very large capacity and function as a “depot.” When a volatile agent is stored in a “depot,” it is essentially diverted from the brain (site of action) and decreases the speed of induction and emergence. This effect

is accentuated with increased blood:gas solubility or increased duration of administration (MAC-hr). – Partition coefficients: The ratio of the amount of substance present in one phase compared with another (assumes 2 phases at equal volume and specified temperature). Allows an assessment of relative solubilities between blood and gas, brain, muscle, or fat (provides a means to assess and compare the quantity and time needed for uptake and saturation of a tissue). For example, halothane’s blood–gas partition coefficient is 2.4; thus, at equilibrium, its concentration in blood is 2.4 times greater than in gas in contact with the blood (e.g., in the alveoli). – Fi is the inspired concentration of volatile agents. It is affected by fresh gas flow rates, concentration of agent delivered, ventilation (rate, tidal volume), volume of the breathing system (circuit length and diameter), and absorption (circuit, machine). Fi is increased

with increased fresh gas flow rates, concentration delivered, and ventilation as well as decreased breathing circuit volume and absorption. – FA is the alveolar concentration of a volatile agent. FA is affected by Fi (input) as well as factors affecting uptake from the lungs (output). Uptake is affected by the blood:gas solubility, cardiac output, and the venous–arterial partial pressure difference. At equilibrium FETagent ∼ FA ∼ Fblood ∼ Fbrain, and an assessment of anesthetic depth

(induction, maintenance, and recovery) can be extrapolated from FA. FA (and rate of

induction) is increased with poorly soluble gases, impaired cardiac output, decreased alveolar blood flow, and small venous–arterial partial pressure differences. Note that FA is indirectly measured by end tidal monitors that reflect alveolar concentrations (FETagent).

– FA/Fi ratio: By convention, ratio is <1 due to uptake of the anesthetic agent by the

pulmonary circulation; if no uptake exists, it would equal 1, but it is not possible to exceed 1 on induction or maintenance. FA/Fi ratio provides a method to assess the speed

of onset. – Elimination: Recovery depends on lowering the volatile concentration in the brain tissue; FA is used as a surrogate indicator of Fbrain (FETagent ∼ FA ∼ Fblood ∼ Fbrain). Volatile

agents are eliminated by exhalation, biotransformation, and transcutaneous loss. Factors that speed up induction can also speed up recovery: Increased fresh gas flow, decreased anesthesia machine-circuit volume and absorption, decreased solubility, increased cerebral blood flow, and increased ventilation. • 1 MAC is the alveolar concentration of the volatile agent, at 1 atmosphere, that is required to produce immobility in 50% of patients at skin incision. – Determination of the value: After equilibration of the agent, subjects were exposed to a single skin incision and then observed for purposeful movement in response to the noxious stimuli. – At equilibrium, measurements of expired gases can be extrapolated to alveolar MAC, and hence, blood and brain tissue levels. Perioperatively, there is no current method to directly measure brain tissue concentration or alveolar concentration. – 1 MAC, however, does not reflect an individual’s response, and additionally, it does not guarantee amnesia.

DISEASE/PATHOPHYSIOLOGY

• Factors increasing MAC. – Infants: Generally higher, the exception being neonates which have a lower MAC value. The MAC value peaks at approximately 6 months of age (3). – Hyperthermia – Chronic alcoholism – Thyrotoxicosis – Hypernatremia – Genetic factors: Patients with red hair have an approximately 19% increased requirement. – Sympathetic drugs: Monoamine oxidase inhibitors (MAOIs) Tricyclic antidepressants (TCAs) Acute cocaine Acute amphetamines Ephedrine Levodopa • No effect on MAC – Duration of anesthesia – Gender – Hypocarbia and mild hypercarbia • Factors decreasing MAC: – Increasing age: MAC decreases by approximately 6% per decade (3) – IV anesthetics such as dexmedetomidine, propofol, ketamine, barbiturates, clonidine – Anxiolytics – Narcotics – IV local anesthetics such as lidocaine – Hypothermia: For every 10°C decrease, there is a 50% decrease – Acute alcohol intoxication – Pregnancy: After ~8 weeks of gestation, decreases are seen. Levels can decrease by up to 30% during pregnancy and return to normal within 3 days postpartum (4). – Hypotension (MAP <40 mm Hg) – Hyponatremia – Metabolic acidosis – Anemia (hematocrit <10%) – Hypercarbia (paCO2 >95 mm Hg) – Hypoxia (paO2 <38 mm Hg)

PERIOPERATIVE RELEVANCE

• MAC is an additive value and provides a point of reference for the varying stages of anesthesia. The caveat is that MAC is independent of other factors that may or may not be taken into account and is based on the average individual in the population. As with most averages, there are outliers (1). • MAC-95 is the alveolar concentration at which 95% of patients will not move in response to surgical stimuli (skin incision). It is measured at approximately 1.2–1.3 MAC for isoflurane,

sevoflurane, and desflurane. • MAC BAR is the alveolar concentration at which 50% of patients do not exhibit a sympathetic response (heart rate, blood pressure, noradrenaline levels) to surgical stimulation. It is approximately 1.6 MAC for isoflurane, sevoflurane, and desflurane. • MAC BAR95 is the alveolar concentration where 95% of patients do not exhibit a sympathetic response to surgical incision. • MAC EI is the alveolar concentration to prevent laryngeal response to endotracheal tube intubation. It is approximately 1.3 MAC for isoflurane, sevoflurane, and desflurane. • MAC-hour is the MAC time for exposure to the volatile agent; MAC is multiplied by hour increments. For example, 1.25 MAC for 2 hours represents 2.5 MAC-hours. It is used as a comparative measure of exposure when calculating adverse effects and setting dose-limits. It does not account for difference in metabolism, effects at different concentrations, and fresh gas flow. • MAC-awake is the alveolar concentration at which 50% of patients voluntarily respond (open eyes) to verbal command. It is NOT equivalent to MAC aware/recall. It is measured as approximately 0.3–0.4 MAC for isoflurane, sevoflurane, and desflurane and approximately 0.5 MAC for nitrous oxide and halothane. • MAC-aware is the MAC value at which 50% of patients are aware of surgical events despite some anesthetic being on board. MAC-aware is generally 0.4–0.5. However, for 95% confidence, the MAC value for awareness is generally up to ∼25% higher.

GRAPHS/FIGURES See Table

REFERENCE

1. Quasha AL, Eger EL II, Tinker JH. Determination and applications of MAC. Anesthesiology. 1980;53:315–334. 2. Yasuda N, Lockhart SH, Eger EI. Kinetics of desflurane, isoflurane, and halothane in humans. Anesthesiology. 1991;74:489–498. 3. Lerman J, Schmitt-Bantell BI, Gregory GA. Effect of age on the solubility of volatile anesthetics in human tissue. Anesthesiology. 1986;65:307–311. 4. Chan MTV, Gin T. Postpartum changes in the minimum alveolar concentration of isoflurane. Anesthesiology. 1995;85:1360–1363.

ADDITIONAL READING

• Barash PG, Cullen BF, Stoelting RK. Clinical Anesthesia. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2006. • Chestnut DH. Obstetric Anesthesia. 3rd ed. Philadelphia: Elsevier-Mosby: 2004. • Eger EI, Eisenkraft JB, Weiskopf RB. The pharmacology of inhaled anesthetics, Dannemiller; 2002.

See Also (Topic, Algorithm, Electronic Media Element) • Awareness under anesthesia

• FAlveolar

CLINICAL PEARLS

• MAC is the minimum concentration of gas where 50% of average patients do not move in response to a surgical stimulus. • MAC is affected by many factors including age and concomitant drug administration.

MINUTE VENTILATION Stephane Ledot, MD Yoram G. Weiss, MD, MBA, FCCM

BASICS DESCRIPTION

• Minute ventilation (MV) is the volume of all inhaled or exhaled gas in one minute. It is calculated by the multiplication of the tidal volume (VT) and respiratory rate (RR): MV = VT × RR.

• During spontaneous ventilation, MV is under tight control by the respiratory center in the brainstem. – Central and peripheral feedback mechanisms adjust MV to deliver adequate oxygen to the tissues while removing CO2 from the lungs. – At rest, for an average adult, normal tidal volume is ∼500–600 mL (6–8 mL/kg) and the respiratory frequency is around 12–22 breaths per minute. This results in a normal MV of ∼7–8 liters per minute. • Under general anesthesia, the patient can either breathe spontaneously or be mechanically ventilated. Anesthetic agents have dose-dependent effects on the medullary respiratory center that affect MV in both the spontaneously ventilating and postoperative patient.

PHYSIOLOGY PRINCIPLES

• MV in the spontaneously ventilating (SV) patient is tightly regulated by the respiratory control center, located in the medulla oblongata. It receives afferent input from mechanoreceptors, chemoreceptors, baroreceptors, and proprioceptors, as well as voluntary control from the cerebral cortex and temperature. • Brainstem respiratory control center is divided into the: – Inspiratory center: Efferent nerves stimulate spontaneous and rhythmic contraction of the diaphragm (phrenic nerves) and intercostal muscles. The apneustic center, located in the pons, provides a constant stimulus to the inspiratory center and is inhibited by the pneumotaxic center. The pneumotaxic center, also located in the pons, provides inhibitor impulses that limit phrenic nerve contraction and overdistension. It antagonizes the apneustic center (constant stimulus) and decreases tidal volume; the absence of the pneumotaxic center would result in increased tidal volume and decreased RR. The Hering–Breuer reflex consists of afferent receptors located in the bronchi and bronchioles that are activated by stretching and non-stretching. Efferent impulses are transmitted via the vagus nerve to the respiratory center. Thus, inflation acts to inhibit inhalation and prevent further inflation. As the expiratory phase begins, the receptors are no longer stretched, impulses are no longer sent, and inhalation can begin again. – Expiratory center: Under normal, resting conditions, expiration is a passive process via

relaxation of the diaphragm and intercostals as well as elastic recoil of the lungs; there is no activity within the expiratory center. With “fight or flight,” the center stimulates forceful expiration by contraction of the abdominal and internal intercostals. • Afferent input to the respiratory center. – Chemoreceptors: Function to maintain carbon dioxide, pH, and oxygen homeostasis by adjusting the rate, depth, and rhythm of respiration. Central chemoreceptors are cells located in the ventrolateral medulla (surface of the fourth ventricle) that are sensitive to the pH of the cerebrospinal fluid (CSF); they provide feedback to the medullary respiratory center. An acidic CSF stimulates increases in MV, whereas an alkalotic CSF inhibits the inspiratory center. Peripheral chemoreceptor cells are located in the carotid bodies and aortic arch and respond to O2 and CO2 concentrations in the arterial blood;

they transmit information via the glossopharyngeal nerve (IX) and the vagus nerve (X), respectively, to the respiratory center; their feedback regulates the MV on a breath by breath basis. – Baroreceptors: The most important groups are situated in the carotid sinus and aortic arch. An increase in arterial blood pressure can cause reflex hypoventilation or apnea. Conversely, hypotension elicits a sympathetic baroreceptor reflex. – Proprioceptors are located in muscles, tendons, and joints that sense movement. During “fight or flight,” these receptors transmit signals to the respiratory center that increase the RR and tidal volume. – Cerebral cortex: Voluntary control can be exerted to take deep, slow breaths. – Temperature: In hypothermic states, MV decreases via: Impairment of synaptic transmission. Decreased velocity of neuronal conduction; the ventral surface of the medulla is particularly prone. Respiratory muscles and motor neurons do not appear to be affected by hypothermia. • Ventilation: The relationship between ventilation and PaCO2 is described as follows: PaCO2 = (k) (VCO2)/VA, where k is a constant that corrects for the units (k = 0.863), VCO2 is the

metabolic production of carbon dioxide, and VA is alveolar ventilation. To maintain homeostasis, increases or decreases in the PaCO2 are met by respective increases or decreases in VA.

• Composition of the MV is equal to the sum of alveolar ventilation and dead space ventilation. – Alveolar ventilation (VA): The volume of inspired gases reaching the alveoli and taking

part in gas exchange in one minute. – Dead space (VD): The volume of inspired gas that does not participate in gas exchange. It comprises gases in non-respiratory airways (conducting airways also known as anatomic dead space) and alveoli that are not perfused (alveolar dead space).

Pregnancy Considerations

• A progressive increase in MV starts soon after conception and peaks at 50% above normal levels around the second trimester.

– Oxygen consumption increases gradually in response to the needs of the growing fetus, culminating in a rise of at least 20% at term. During labor, oxygen consumption is further increased (up to 60%) as a result of the exaggerated cardiac and respiratory work load. – Progesterone stimulates ventilation by lowering the CO2 threshold of the respiratory center and may also act as a primary stimulant. – There is a 40% rise in TV and 15% rise in RR. Since dead space remains unchanged, alveolar ventilation is about 50% higher at the end of gestation. – Because the increase in MV exceeds the CO2 production, the normal PaCO2 decreases to ∼32 mm Hg. The increased secretion of renal bicarbonate partially compensates for the hypocarbia so that pH increases only slightly (from 7.42 to 7.44).

Pediatric Considerations

• The increased MV is in response to the increased metabolic demands of growth. – In neonates, the oxygen consumption is 4–6 mL/kg (compared to 2 mL/kg in adults). – MV is 200 mL/kg/min in the newborn compared to 100 mL/kg/min at puberty. Alveolar ventilation is also double of that of an adult. – Tidal volume remains constant at 7 mL/kg throughout life, with the increase in MV primarily from an increase in RR. In neonates, the RR is ∼ 3 times that of an adult (∼30 breaths/minute) and progressively falls to adult values at adolescence. – Immature respiratory control is responsible for an increased risk of postoperative severe hypoventilation and apnea in preterm infants.

Geriatric Considerations

• In the elderly patients, MV at rest is maintained despite decreases in tidal volume secondary to increased RR. These changes are due to decreases in chest wall compliance as well as changes in the function of central chemoreceptors and peripheral mechanoreceptors in the chest wall and lung parenchyma. A reduction of 50–60% in the ventilatory response to hypoxia and hypercapnia is observed.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Alveolar hypoventilation: Normal and continued removal of CO2 from the blood is dependent on adequate MV. In the event that VA is affected, or does not adequately complement changes in PaCO2, a respiratory acidosis or alkalosis may result.

• Obesity hypoventilation syndrome (OHS) or Pickwickian syndrome: Defined as a combination of obesity (BMI >30 kg/m2) and awake arterial hypercapnia (PaCO2 >45 mm

Hg) in the absence of other known causes of hypoventilation. Although the precise mechanism is unknown, it is believed to result from the combination of: – Impaired respiratory mechanics reflective of a restrictive ventilatory defect: OHS patients have decreased total lung capacity, vital capacity, functional residual capacity, and compliance as well as increased residual volume, work of breathing, and airway resistance. – Abnormal medullary respiratory center control: OHS patients appear to lack a compensatory increased ventilatory drive to offset the effects of the mechanical

restrictions of obesity. Conversely, obese patients without OHS appear to have an augmented ventilatory response. – Neurohormonal aberrancies: Leptin is normally produced by the adipose tissue and acts on the central respiratory center to stimulate ventilation. In OHS patients, there appears to be a leptin deficiency that results in hypoventilation. • COPD: Hypoventilation is secondary to multiple mechanisms. Patients usually present with severe airway obstruction as well as a decreased responsiveness to hypoxia and hypercapnia. In advanced stages, or periods of decompensation, tidal volume is decreased, RR is increased, and work of breathing is increased resulting in a rapid shallow respiratory pattern. In addition, diaphragmatic dysfunction may result from muscle fatigue and limited movement, leading to an increased VD/VA. In patients with airflow obstruction, inhomogeneities in ventilation are responsible for the increase in dead space.

PERIOPERATIVE RELEVANCE

• General anesthesia. – Equipment or apparatus dead space is increased and can be clinically relevant in low MV ventilation states or in pediatrics. To avoid hypercarbia and acidosis, measures to decrease the dead space volume or increase MV need to be adjusted accordingly. – Inhaled anesthetics produce dose-dependent and drug-specific effects on the breathing pattern, ventilatory response to CO2 and hypoxemia, and airway resistance. The net effect is a rapid and shallow pattern of breathing, a net decrease in MV, and increase in the PaCO2.

Tidal volumes are decreased via direct depression of the medullary respiratory center (central effect), as well as impaired intercostal muscle and diaphragm function (peripheral effect). There is reduced activity of the pre-Bötzinger complex situated in the ventrolateral medulla of the brainstem; this area is assumed to be the core of the respiratory rhythm generation (respiratory pacemaker). The GABA agonist effect inhibits both inspiratory and expiratory neurons. – Intravenous anesthetics: Propofol, barbiturates, and benzodiazepines, with the exception of ketamine, produce central nervous system depression via their ability to enhance the effects of the inhibitory neurotransmitter GABA and depress the respiratory centers. These agents block mechanoreceptor transmission to the respiratory centers and provoke an apneustic breathing pattern. They also cause a depressant effect on bulbospinal expiratory neurons due to their inhibition of the NMDA receptor. – Opioids produce dose-dependent depression of the respiratory rate with compensatory increases in the tidal volume; apnea results at high doses. Effects are primarily through: An antagonist effect on the medullary respiratory center (mediated by the μ opioid receptors) as well as the pre-Bötzinger complex in the ventrolateral medulla. Also affects the Kölliker-Fuse and parabrachial nucleus of the dorsolateral pons (pneumotaxic centre). • Neuraxial anesthesia: Spinal and epidural anesthesia have very little effect on the pulmonary function (lung volumes, resting MV, dead space, and shunt fraction). In the event of a high block, active inspiratory volumes could be affected by abdominal muscle paralysis. This

effect may be more pronounced in patients with pulmonary disease (e.g., COPD) that rely on accessory muscles to maintain the MV. In addition, neuraxial opioids (intrathecal and epidural) can result in immediate or delayed respiratory depression.

EQUATIONS

• MV = VT × RR; where MV is minute ventilation, VT is tidal volume, and RR is respiratory

rate. • PaCO2 = (k)(VCO2)/VA; where PaCO2 is the partial pressure of carbon dioxide in the

arterial blood, k is a constant that corrects for units (k = 0.863), VCO2 is the metabolic

production of carbon dioxide, and VA is alveolar ventilation.

REFERENCES

1. Quanjer PH, et al. Lung volumes and forced ventilatory flows. Report Working Party ‘Standardization of Lung Function Tests’. European Community for Steel and Coal. Eur Respir J Sippl. 1996;16:5–40. 2. Powell FL, et al. Comparative physiology of lung complexity: Implications for gas exchange. News Physiol Sci. 2004;19:55–60.

3. Hendenstierna G, et al. The effects of anesthesia and muscle paralysis on the respiratory system. Intensive Care Med. 2005;31:1327–1335. 4. Yamakaye M, et al. Changes in ventilatory pattern and arterial oxygen saturation during spinal anesthesia in man. Acta Anaesthesia Scand. 1992;35:569–571. 5. Douglas NJ, et al. Respiration during sleep in normal man. Thorax. 1982;37:840–844. 6. Hegewald MJ, et al. Respiratory physiology in pregnancy. Clin Chest Med. 2011;32:1–13. 7. Barnes PJ, et al. Chronic obstructive pulmonary disease. N Engl J Med. 2000;343(4):269– 280. 8. Berger AJ, et al. Regulation of respiration. N Engl J Med. 1977;297(4):194–201. 9. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med. 2005;118:948– 956.

ADDITIONAL READING

• Guyton and Hall. Textbook of Medical Physiology. 12th ed. Saunders Elsevier; 2011. • John B West. Respiratory physiology: The essentials. 8th ed. Lippincott Williams and Wilkins; 2008.

See Also (Topic, Algorithm, Electronic Media Element) • Dead space • Mechanical ventilation • Tidal volume • Carotid body • Respiratory acidosis • Respiratory alkalosis

CLINICAL PEARLS

• MV is the product of tidal volume and respiratory rate and is ∼7–8 liters per minute for a normal adult. • Alveolar ventilation is the volume of inspired gases reaching the alveoli and taking part in gas exchange in one minute. • Volatile and intravenous agents, including opioids, have direct and indirect effects on the tidal volume and the respiratory rate. • Physiological and pathophysiological changes in MV produced by induction and maintenance of anesthesia must be understood and addressed to safely maintain adequate gas exchange. Elderly and pregnant patients demonstrate changes in normal physiologic respiratory patterns as do obese and COPD patients.

MITRAL REGURGITATION Brian L. Marasigan, MD

BASICS DESCRIPTION

• The mitral valve, normally consists of two leaflets (bicuspid valve) that open during ventricular diastole and close during systole. During systole, the mitral valve closes and prevents the backflow of blood from the left ventricle (LV) to the left atrium (LA). Closure of the valve helps maintain LV diastolic pressure and volume and thus systemic and coronary perfusion pressure. • Mitral regurgitation (MR) is the presence of a backflow leak through the valvular apparatus during systole. – Ranges in severity from trace, mild, moderate, to severe. Severity is classified by the amount of regurgitant volume, regurgitant orifice area size, and regurgitant fraction by echocardiography. – Acute MR is the sudden onset of symptoms usually due to an acute event such as myocardial infarction and valvular apparatus trauma or disruption. – Chronic MR has a gradual onset and may be sustained for many years and may be compensated or uncompensated. EPIDEMIOLOGY Incidence

• Rheumatic heart disease is the most common cause of MR world-wide; mitral valve prolapse is the most common cause in the US (accounts for 45%). • Mean age of rheumatic MR is 36 years old. • Following a myocardial infarction, 20–30% of patients develop MR.

Prevalence

• Mitral valve prolapse is present in ~4% of the population • Under 20 years of age, males > females • Males >50 years of age have more severe disease

Morbidity

• Acute MR has a higher rate of morbidity and mortality due to the pathophysiology. Acute congestive heart failure (CHF) and cardiogenic shock may occur. Operative mortality is near 80%. • Chronic MR may be asymptomatic for years. Chronic severe MR will lead to eventual decompensation with diastolic and systolic dysfunction and CHF. • Surgical management becomes the common end point to both acute and chronic MR. • Global and regional left atrial (LA) functions are altered in patients with chronic MR secondary to myxomatous mitral valve disease (1)[C].

• Left ventricular dysfunction may be present with MR and may be underestimated in severe MR. The decreased after load on the LV with backward flow through the mitral valve gives the false appearance of normal function. In severe MR, a low LV ejection fraction carries a very poor prognosis.

Mortality

• MR due to flail leaflets and LA diameter of >55 mm is associated with increased mortality under medical management (2)[B]. • Mild MR is an independent predictor of post-MI mortality. • Atrial fibrillation was identified by multivariate logistic regression analysis as a predictor of in-hospital death after non-cardiac surgery; OR 11.579 (3)[B].

ETIOLOGY/RISK FACTORS

May be associated with any condition that alters mitral valve closure. Organic, also known as intrinsic valve disease, may be due to myxomatous changes, rheumatic heart disease, mitral valve prolapse, or calcific valve disease. Functional MR results from a non-valvular disease such as dilated cardiomyopathy, causing incomplete closure of the mitral valve. PATHOPHYSIOLOGY

• Acute MR is often due to ruptured chordae or papillary muscle resulting in an acute increase in LV diastolic volume, LA volume, LV ejection fraction (EF), and aortic systolic pressure. Acute fulminant CHF may ensue and is marked by a decrease in contractility and EF. Mitral valve prolapse and tissue diseases (e.g., rheumatic heart disease, myxomatous disease) may present with an acute phase that is often milder in onset and leads to chronic MR. • Chronic MR has a more insidious onset and may take months to years to become symptomatic. Eccentric left ventricular hypertrophy, atrial enlargement, and increased heart rate compensate for the extra volume of regurgitation; ejection fraction is maintained and symptoms typically do not appear without exertion or positional changes. As regurgitant volume and MR worsen over time, the left ventricle decompensates. The ventricle becomes too enlarged and the increased wall stress and decreased myocardial perfusion lead to diminishing EF and CHF, end organ hypoperfusion, decreased coronary perfusion pressure, increased myocardial oxygen demand, and cardiogenic shock. In addition, increases in LA pressure lead to pulmonary congestion and eventually chronic decompensated CHF with right ventricular failure. LA enlargement leads to atrial fibrillation which diminishes forward flow and increases the risk of thrombus formation. Sympathetic stimulation increases systemic vascular resistance to maintain pressure but worsens MR. Without timely surgical repair, the heart may not be able to significantly recover.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintenance of cardiac output, coronary perfusion, and prevention of cardiac decompensation are the primary goals. • Maintain high-normal sinus rhythm to minimize regurgitant time and excessive left ventricular filling. • Systemic vascular resistance may be decreased, but should be balanced between facilitating forward flow (decreasing regurgitation) and maintaining adequate coronary and systemic

perfusion pressure. • Careful fluid management and inotropic support to prevent cardiovascular overload or collapse. • Decrease pulmonary hypertension by avoiding increased pulmonary vascular resistance from hypoxia, hypercapnia, acidosis, and pulmonary vasoconstrictors. • Maintain contractility with inotropes if unresponsive to volume and afterload changes.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Shortness of breath • Fatigue • Dyspnea on exertion • Palpitations • Orthopnea • Angina

History

• Family history of cardiac valvular disease, collagen or connective tissue disease, or congenital malformations. • History of rheumatic disease or risk factors for endocarditis. • Commonly diagnosed after symptomatic exercise or during work up for diastolic or systolic CHF. • May be discovered early after detailed physical exam and heart auscultation of murmur. • Usually classified by echocardiographic measurement of color Doppler flow across the valve.

Signs/Physical Exam

• Systolic murmur • Signs of congestive heart failure • Endocarditis • Cyanosis

TREATMENT HISTORY

• Medical management of angina, CHF, diabetes, hypertension, and hyperlipidemia, if associated. • Balloon mitral valvuloplasty or valve replacement. • Previous treatment of infective endocarditis. • Anticoagulation or ablation for atrial fibrillation.

MEDICATIONS

• Antihypertensives including calcium channel blockers and avoiding beta-blocker bradycardia. • Anti-anginals including nitrovasodilators. • Heart failure treatments including digoxin, ACEI/ARB, and diuretics. • Statin therapy if indicated.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Basic metabolic profile: Monitoring electrolytes and the kidney function. • Complete blood count: Monitoring for preoperative infection and hematocrit and platelet counts adequate for surgery. • Basic coagulation studies: Evaluation of liver function and adequate levels for surgery. • Electrocardiogram: Diagnosis of arrhythmia and ischemic changes. • Chest X-ray: Cardiopulmonary status • CT scan for evaluation of aorta. • Echocardiogram: Diagnosis and classification of disease severity and ventricular function.

CONCOMITANT ORGAN DYSFUNCTION

• Concomitant mitral stenosis or aortic valve disease in rheumatic heart disease • Ischemic cardiomyopathy or hypertrophic cardiomyopathy • Hypertension • Pulmonary hypertension, congestion, and pleural effusion • Renal insufficiency

CIRCUMSTANCES TO DELAY/CONDITIONS

• Severe decompensated symptomatic MR with decreased left ventricular function for noncardiac surgery • Recent MI or stroke • Sepsis or infection • Unrelated end organ failure

CLASSIFICATIONS

Severe mitral regurgitation criteria: • >60 mL regurgitant volume • >50% regurgitant volume • Effective regurgitant orifice area >0.4 cm2 • Color Doppler vena contracta >0.7 cm • Pulmonary vein flow reversal on ventricular systole • Severe LA enlargement • MR jet ‘V’ wave and PCWP cannon “V” wave

TREATMENT PREOPERATIVE PREPARATION Premedications

Midazolam to prevent anxiety and increased sympathetic tone. Special Concerns for Informed Consent

Risk for intraoperative stroke, myocardial infarction, and death should be discussed.

INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on the procedure; sedation, general (endotracheal tube or laryngeal mask airway), and regional anesthesia may be utilized. • Neuraxial techniques can result in a sympathectomy and facilitate forward flow (reduce regurgitation), but may reduce coronary perfusion pressure.

Monitors

• Standard ASA monitors. • Invasive monitors may be chosen based upon the severity of MR and the surgical procedure: 5 lead EKG, arterial line, central venous catheter, pulmonary artery catheter, transesophageal echocardiogram or less invasive cardiac output monitors.

Induction/Airway Management

• Smooth controlled induction to maintain vital signs within normal limits. • Anticholinergic medications may be administered to maintain high-normal heart rate.

Maintenance

• Volatile anesthetics, intravenous, or a combination may be utilized. Reductions in systemic vascular resistance are desirable to facilitate forward flow; however, adequate cerebral and coronary perfusion should be ensured. Total intravenous techniques may be associated with bradycardia, particularly if utilizing high doses of remifentanil. • Fluid balance includes maintaining normal preload and a hematocrit >24–30% to optimize forward flow and myocardial oxygen balance. Excessive preload may add to regurgitant volume and cause LV failure.

Extubation/Emergence No additional concerns

POSTOPERATIVE CARE BED ACUITY

Depends on surgical procedure and severity of underlying disease. MEDICATIONS/LAB STUDIES/CONSULTS

Standard postoperative fluid and electrolyte management and related laboratory studies. COMPLICATIONS

Perioperative arrhythmia

REFERENCES

1. Moustafa SE, et al. Global left atrial dysfunction and regional heterogeneity in primary chronic mitral insufficiency. Eur J Echocardiogr. 2011; 12(5):384–393. 2. Rusinaru D, et al. Left atrial size is a potent predictor of mortality in mitral regurgitation

due to flail leaflets: Results from a large international multicenter study. Circ Cardiovasc Imaging. 2011; 4(5):473–481. 3. Lai HC, et al. Mitral regurgitation complicates postoperative outcome of noncardiac surgery. Am Heart J. 2007;153(4):712–717. 4. Grigioni F, et al. Ischemic mitral regurgitation: Long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103:1759–1764.

ADDITIONAL READING

• 2006 American College of Cardiology/American Heart Association guidelines.

CODES ICD9 • 394.1 Rheumatic mitral insufficiency • 424.0 Mitral valve disorders • 746.6 Congenital mitral insufficiency ICD10 • I05.1 Rheumatic mitral insufficiency • I34.0 Nonrheumatic mitral (valve) insufficiency • Q23.3 Congenital mitral insufficiency

CLINICAL PEARLS

• Etiologies of mitral regurgitation are either: – Organic from intrinsic valvular causes such as myxomatous, rheumatic, or calcific disease. – Functional from non-valvular causes such as dilated cardiomyopathy that result in incomplete closure. • Mitral regurgitation is described based upon onset: – Acute: life-threatening and may require immediate surgical management. – Chronic: requires medical or surgical management and may be asymptomatic until late stages. • Severity is classified by echocardiographic criteria. Severe MR will have a regurgitant volume that is >60 mL or >50%, or an effective regurgitant orifice area >0.4 cm2. Significant signs and symptoms are present (shortness of breath, systolic and diastolic congestive heart failure).

MITRAL STENOSIS Brian L. Marasigan, MD

BASICS DESCRIPTION

• Mitral valve stenosis (MS) is a narrowing of this area at the valve itself. New criteria for diagnosis of severe mitral stenosis includes an open area of <1.0 cm2 with a transvalvular mean gradient of >10 mm Hg, although symptoms may begin at much earlier stages of stenosis. EPIDEMIOLOGY Incidence

Most common after rheumatic fever with a latency period of 10–25 years in under-developed countries to 20–40 years in developed countries. Prevalence

• Women: 1.6% • Men: 0.4% (1)[B]

Morbidity

• Risk for congestive heart failure, atrial fibrillation, thromboembolism, stroke, pulmonary hypertension, right-sided heart failure, and pulmonary edema. • Mitral stenosis with atrial fibrillation increases the risk of stroke 7–15% per year (2)[B]. • Mild to moderate MS may be asymptomatic except during exertion, while severe MS symptoms occur at rest. • LV dysfunction may occur in 30% of MS patients. Mortality

2-year mortality for infants with severe congenital MS is 40% (3)[B].

ETIOLOGY/RISK FACTORS

• Majority of cases are due to rheumatic fever and resultant rheumatic heart disease. • Severe mitral calcification and congenital mitral stenosis are uncommon causes.

PATHOPHYSIOLOGY

• The basic pathophysiology of MS stems from obstruction of left ventricular filling with a highly resistant valve opening. The disease process progresses as follows: – Initially, the resistance to left ventricular filling is compensated by left atrial hypertrophy (enhanced atrial kick). – With time, the left atrium begins to dilate to handle the increase in volume – However, the volume overload eventually overwhelms the left atrium and LV filling

becomes impaired. Fluid backs up into the pulmonary vasculature leading to pulmonary congestion, left congestive heart failure, and resultant right heart failure. • Left atrial enlargement increases the risk for developing atrial fibrillation. In addition, the decreased flow state increases the risk for thrombus formation. • Normal sinus rhythm and a slow rate are desired to allow time for forward flow and filling of the left ventricle

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Primary goals are the maintenance of: – Cardiac output – Coronary perfusion (diastolic perfusion pressure) – Normal and slow sinus rhythm – Volume status – Prevention of cardiac decompensation • Inotropic support may be necessary to prevent cardiovascular overload or collapse. Vasopressor support and fluid maintenance may help maintain preload and coronary perfusion pressure. • Pulmonary hypertension is a major concern and may persist after mitral valve repair. Resulting right ventricular (RV) dysfunction may be a greater concern than left ventricular (LV) dysfunction.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Severity of symptoms may be classified by NYHA I–IV. • Exertional shortness of breath, orthopnea, fatigue, palpitations, and rarely chest discomfort. • Severe symptoms occur from pulmonary edema, pulmonary hypertension, and decreased cardiac output with resultant dyspnea, angina, cough, and hemoptysis.

History

Commonly diagnosed after symptomatic exercising, during work up for diastolic or systolic CHF, or new onset atrial fibrillation. Signs/Physical Exam

• Mid-diastolic murmur with opening S2 snap. • Congestive heart failure (jugular venous distention, pitting edema, shortness of breath) and increased sympathetic tone (cool extremities, hypertension, etc.). • In infants: Cyanosis, poor growth, shortness of breath.

TREATMENT HISTORY

• Balloon mitral valvuloplasty or valve replacement • Atrial fibrillation: Ablation

MEDICATIONS

• Beta blockers to maintain a slow normal sinus rhythm.

• Heart failure treatments including digoxin and ACEI/ARBs, diuretics, nitrates. • Anticoagulants to prevent or treat thrombus. • Atrial fibrillation: Amiodarone, beta blockers, calcium channel blockers.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Basic metabolic profile: Electrolytes and kidney function aid with perioperative management and risk stratification (renal failure carries an increased risk of mortality). • Complete blood count: Preoperative infection, hematocrit, and platelet counts adequate for surgery. • Basic coagulation studies • Chest X-ray: Active congestive heart failure. • Transesophageal echocardiogram: Diagnosis and classification of disease severity and ventricular function. • Cardiac catheterization: Cardiac function and pulmonary pressure evaluation.

CONCOMITANT ORGAN DYSFUNCTION

• Cardiac: Left ventricular dysfunction, hypertension; mitral regurgitation (due to poor valve closure); aortic stenosis or regurgitation in rheumatic heart disease. • Pulmonary: Hypertension, congestion, and pleural effusion.

CIRCUMSTANCES TO DELAY/CONDITIONS • Decompensated congestive heart failure • Sepsis or infection

CLASSIFICATIONS

• Based upon echocardiographic or cardiac catheterization measurements of valve area and transvalvular pressure gradients. • Mitral stenosis severity by valve area. – Normal: 4–6 cm2 – Mild stenosis: <2.5 cm2 – Moderate stenosis: 1.0–1.5 cm2 – Severe stenosis <1.0 cm2 • Mitral stenosis severity by mean pressure gradient (PG) – Mild stenosis: <5 mm Hg – Moderate stenosis: 5–10 mm Hg – Severe stenosis: >10 mm Hg • Mitral stenosis severity by pressure half time (PHT) – Mild stenosis: 100–150 milliseconds – Severe stenosis: >220 milliseconds

TREATMENT PREOPERATIVE PREPARATION

Premedications

Benzodiazepines may be useful to prevent anxiety and tachycardia. Special Concerns for Informed Consent

• Risk for intraoperative stroke, acute congestive heart failure, myocardial infarction, and death, if increased risk, should be discussed. • Access and monitoring line placement, if needed.

INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on the procedure; sedation, general anesthesia (endotracheal tube or laryngeal mask airway (LMA), and regional techniques may be utilized. • Neuraxial techniques can result in a sympathectomy and decreased systemic vascular resistance that can impair coronary perfusion and decrease venous return (preload). It may be considered in mild or moderate MS. Epidurals allow for slow bolusing and time for fluid loading and treatment of hypotension with vasopressors. Carefully confirm appropriate anticoagulation status and profile before proceeding.

Monitors

• Standard ASA monitors • 5 lead EKG: Arrhythmia, ischemia • Arterial line: Beat-to-beat BP monitoring • Invasive monitors may be chosen based on the severity of MS and the surgical procedure.

Induction/Airway Management

Smooth, controlled induction to maintain vital signs within normal limits (heart rate and systemic vascular resistance) and allow time for treatment. Maintenance

• Volatile anesthetics, intravenous, or a combination may be utilized. The specific drug is less important than the overriding goal: maintain normal sinus rhythm, systemic vascular resistance, contractility, and preload. Anesthetic agents can decrease vascular resistance and need to be titrated appropriately, co-administered with phenylephrine, or co-administered with other adjunctive agents (e.g., opioids) to decrease the total dosage. • Adequate preload is essential to maintaining a stable cardiac output. Left ventricular filling is impaired with right ventricular and left atrial dysfunction thus predisposing to pulmonary edema. • Maintenance of normal sinus rhythm is achieved by minimizing cardiac stress and avoiding pro-arrhythmic drugs. – Caution should be exercised when administering powerful chronotropes or anticholinergics. Tachycardia increases myocardial oxygen consumption, decreases diastolic time, and decreases LV filling. – Hypotension and hypertension should be managed with rate and rhythm in mind. All inotropes and vasopressors may be used with caution.

– Ischemia usually occurs with arrhythmia, tachycardia, or hypotension, and the treatment usually lies in the reversal of those conditions. • Hyperoxia, hypocarbia and pulmonary vasodilators may improve pulmonary resistance.

Extubation/Emergence

• Avoid tachycardia and hypotension; consider having rapid onset and short-acting beta blockers and antihypertensives immediately available. • Standard extubation criteria.

POSTOPERATIVE CARE BED ACUITY

Depends on the surgical procedure, severity of underlying disease, and intraoperative events. MEDICATIONS/LAB STUDIES/CONSULTS

Cardiology consultation may be considered in severe diseases if ischemic events occur intraoperatively. COMPLICATIONS

• Perioperative arrhythmia • Mental status changes and stroke • Myocardial infarction

REFERENCES

1. Movahed MR, et al. Increased prevalence of mitral stenosis in women. J Am Soc Echocardiog. 2006; 19:911–913. 2. Carabello BA. Modern management of mitral stenosis. Circulation. 2005;112:432–437. 3. Moore P, et al. Severe congenital mitral stenosis in infants. Circulation. 1994;89:2099– 2106.

ADDITIONAL READING

• Nishimura RA, et al. ACC/AHA 2008 Guideline update on valvular heart disease: Focused update on infective endocarditis: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52(8):676–685.

See Also (Topic, Algorithm, Electronic Media Element) • Mitral regurgitation • Mitral valve replacement • Atrial fibrillation • Pulmonary hypertension • Congestive heart failure • Left ventricular end diastolic pressure (LVEDP)

CODES ICD9

• 394.0 Mitral stenosis • 424.0 Mitral valve disorders • 746.5 Congenital mitral stenosis ICD10 • I05.0 Rheumatic mitral stenosis • I34.2 Nonrheumatic mitral (valve) stenosis • Q23.2 Congenital mitral stenosis

CLINICAL PEARLS

• Mitral stenosis is most commonly an acquired disease but may be related to congenital malformations and rheumatic heart disease. • Significant signs and symptoms include shortness of breath, fatigue, palpitations, diastolic and systolic congestive heart failure, and thromboembolism. • Severity is classified by valve area and transvalvular gradients. Severe disease is defined as a valvular area <1.0 cm2 and mean PG of >10 mm Hg • Maintenance of general anesthesia includes supporting cardiac diastolic function, optimizing fluid management, sustaining a normal and slow sinus rhythm, and monitoring for arrhythmia and pulmonary edema.

MITRAL VALVE PROLAPSE Alain A. Salvacion, MD James D. Boone, MD

BASICS DESCRIPTION

• Mitral valve prolapse (MVP) is the systolic displacement of varying portions of one or both of the mitral, bicuspid leaflets above the mitral annulus into the left atrium. • Echocardiographic MVP is defined as single or bileaflet prolapse at least 2 mm above the annular plane, with or without leaflet thickening. EPIDEMIOLOGY Incidence

Equally distributed between men and women; more common in young women, but higher incidence of complications in men. Prevalence

• Most commonly diagnosed cardiac valvular abnormality. • 2–3% of the general population based on current criteria. • MVP in Marfan syndrome is reported to be between 40 and 80%

Morbidity

• Most patients are asymptomatic. • MVP syndrome includes atypical chest pain, dyspnea, palpitations, syncope, and anxiety. • Serious complications, such as endocarditis, cerebrovascular events, progressive mitral regurgitation (MR), arrhythmias, and sudden cardiac death, are uncommon but related to higher morbidity. • Moderate to severe MR and depressed left ventricular (LV) function are major risk factors for complications. • Mild MR, flail leaflet, left atrial enlargement, atrial fibrillation, and age older than 50 are minor risk factors for complications. Mortality

• Usually has a benign course and excellent prognosis. • Survival rate is similar to that in an age-matched and sex-matched population without MVP.

ETIOLOGY/RISK FACTORS

• Well-recognized association with connective tissue disorders such as Marfan syndrome (∼90% prevalence), Ehlers–Danlos, and osteogenesis imperfecta. • Most cases are sporadic, but can also be familial.

PATHOPHYSIOLOGY

• Related to histological valve tissue abnormalities, geometric discrepancies between the LV and MV, or several connective tissue disorders. • Myxomatous degeneration, characterized by leaflet thickening and redundancy, is the most common and clinically important abnormality.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Distinguish patients with functional MVP from those with advanced disease and associated hemodynamically significant MR. • Patients with functional MVP are younger and have fewer risk factors for anesthesia. In these patients, increased LV emptying should be avoided because this will accentuate MVP and lead to increased MR; therefore, hemodynamic goals should include avoiding the following: – Decreases in LV preload – Decreases in systemic vascular resistance (SVR) – Increases in contractility – Tachycardia • Patients with significant mitral degeneration and associated hemodynamically significant MR are usually older and more likely to have congestive heart failure (CHF). These patients will benefit from hemodynamics that improve forward flow, such as mildly increased heart rate, increased preload, and decreased SVR. • Patients with CHF will benefit from an anesthetic plan that preserves myocardial function.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Assess for symptoms of MVP syndrome. • Assess for symptoms of heart failure such as dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. • Assess for symptoms of arrhythmias such as palpitations.

History

• Age of diagnosis • Complications from MVP, such as endocarditis, cerebrovascular events, MR, and arrhythmias • Associated disorders • Exercise tolerance

Signs/Physical Exam

• Mid-systolic click, often accompanied by a late systolic murmur in mild MVP. • Holosystolic murmur in severe MR; click may also disappear. • S3 and rales seen in CHF. • Other signs of CHF, such as pulmonary edema, JVD, and lower extremity edema. • Look for signs of connective tissue disorders.

TREATMENT HISTORY

• Previous treatment for complications of MVP • Other treatment for associated disorders

MEDICATIONS

• Beta blockers or anti-arrhythmics for arrhythmias • Anti-coagulation, such as aspirin or warfarin for history of CVA • Heart failure medications

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Echocardiography for diagnosis, as well as assessment of LV function and severity of MR. • EKG if there is concern for arrhythmias. • CXR may show pulmonary congestion if the patient is in heart failure. • Other studies dictated by medications and other comorbidities. • Send blood cultures if there is concern for endocarditis.

CONCOMITANT ORGAN DYSFUNCTION

• There is potential for cerebrovascular events. • Other organs (e.g., lungs, liver, and kidneys) can be affected if the patient is in heart failure.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Optimize serum electrolytes to reduce risk of intra-operative arrhythmias. • Optimize volume status if patient is in CHF.

CLASSIFICATIONS

Thickening of leaflets:

• >5 mm: Classic prolapse • <5 mm: Regarded as non-classic

TREATMENT PREOPERATIVE PREPARATION Premedications

• Ensure sufficient anxiolysis to avoid tachycardia, which may reduce LV size and possibly worsen prolapse and regurgitation. • Give premedication judiciously in patients with hemodynamically significant MR and depressed LV function. • Bacterial endocarditis prophylaxis should be considered in patients with mitral valve “click” and regurgitation or high-risk features including: – Prosthetic cardiac valve – Previous endocarditis – Cyanotic congenital heart disease that is unrepaired (including those with palliative shunts and conduits).

– Completely repaired congenital heart disease with prosthetic material or device for the first 6 months post-procedure (either surgical or catheter intervention). – Repaired congenital heart disease with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device. – Cardiac transplantation recipients with cardiac valvular disease.

Special Concerns for Informed Consent Parental consent if a minor. INTRAOPERATIVE CARE Choice of Anesthesia

• Dependent on procedure, provider preference, and patient preference. • Functional MVP without significant MR or LV dysfunction will tolerate all forms of anesthesia. However, those with significant LV dysfunction should be considered for local or peripheral nerve blocks when possible or appropriate.

Monitors

• Dependent on the extent of procedure. • Patients with functional MVP usually do not require invasive monitoring. • Patients with significant MR and LV dysfunction may benefit from an arterial line for continuous blood pressure monitoring and a central line for vasopressor support. Consider a pulmonary artery catheter and/or transesophageal echocardiography (TEE) for cases involving large volume shifts.

Induction/Airway Management

• In patients with functional MVP, avoid hemodynamics that will enhance MVP such as decreases in LV end-diastolic volume, decreases in SVR, increases in contractility, or tachycardia. • In patients with significant MR, hemodynamic goals should promote forward flow such as mildly increased heart rate, increased preload, and decreased SVR while avoiding myocardial depression.

Maintenance

• Minimize sympathetic stimulation and undesirable decreases in LV emptying that may worsen prolapse, as above. • Patients with significant MR will benefit from hemodynamic goals that improve forward flow, as above. • Intra-operative arrhythmias may occur especially in head up positions (presumably due to decrease in preload and accentuation of MVP). Consider beta blockers or lidocaine. • Fluids: Maintenance of a positive fluid balance will help with decreases in preload that may accentuate prolapse or MR.

Extubation/Emergence

Avoid excessive sympathetic stimulation which may worsen prolapse or MR.

POSTOPERATIVE CARE BED ACUITY

• Routine post-operative care in majority of patients. • ICU care for patients with high-risk procedure, hemodynamically significant MR, or poor LV function.

MEDICATIONS/LAB STUDIES/CONSULTS

• Majority of patients with MVP do not require post-operative studies or consults • Repeat echocardiogram in patients undergoing mitral valve repair or replacement

COMPLICATIONS

• Monitor for fluid overload and worsening LV function in patients with poor myocardial reserve. • Patients are at risk for arrhythmias.

REFERENCES

1. HayekE, et al. Mitral valve prolapse.Lancet.2005;365:507–518. 2. Sutton MJ, Weyman A. Mitral valve prolapse prevalence and complications: An ongoing dialogue. Circulation. 2002;106:1305–1307. 3. Freed L, et al. Prevalence and clinical outcome of mitral-valve prolapse. NEJM. 1999;341:1–7. 4. Hanson E, et al. Mitral valve prolapse. Anesthesiology. 1996;85:178–195.

ADDITIONAL READING

• www.americanheart.org • www.mayoclinic.com/health/mitral-valve-prolapse

See Also (Topic, Algorithm, Electronic Media Element) • Mitral valve regurgitation

CODES ICD9 424.0 Mitral valve disorders ICD10 I34.1 Nonrheumatic mitral (valve) prolapse

CLINICAL PEARLS

• It is important to distinguish between patients with functional MVP from those with hemodynamically significant MR and LV dysfunction in order to formulate an appropriate

anesthetic plan.

MITRAL VALVE REPLACEMENT Sascha Beutler, MD, PhD Daniel Castillo, MD

BASICS DESCRIPTION General

• Surgical procedure in which the diseased mitral valve is replaced by a mechanical or biological tissue valve, commonly due to mitral stenosis, regurgitation, or severe prolapse. • Mitral valve (MV) repair, when feasible, is usually preferred over replacement for the surgical treatment of mitral regurgitation (1,2)[A]. Retrospective studies of MV repair appear to demonstrate lower operative mortality, greater improvement in LV function, and higher overall survival at 10 years as compared with MV replacement. • Most often, mitral valve surgery is performed in conjunction with either coronary bypass surgery or another valvular surgery; less frequently, the mitral valve abnormality is an isolated problem requiring cardiac surgery. • Following sternotomy and opening of the pericardium, venous and arterial cannulations are performed. The patient is then taken onto full cardiopulmonary bypass (CPB). After the heart is arrested, the left atrium is opened to expose the mitral valve. The valve leaflets are excised and the annulus is debrided. If feasible, chordae are preserved. The annulus is then measured to properly match the prosthetic valve. Interrupted sutures are placed through the annulus for its entire circumference and then passed through the sewing ring. The prosthesis is securely tied in place. • Systemic warming is initiated during the final stages of the valve implantation. After closure of the left atriotomy, the patient is placed in the head-down position and all remaining air is vented from the left heart through the LV vent. The cross-clamp is removed. Chest tubes are placed and the patient is weaned from bypass. • Minimally invasive mitral valve surgery through smaller incisions with specialized instruments is being explored; for surgery on the valve itself, conventional instruments and techniques are used. Only selected patients are eligible for these approaches. There are, as yet, no randomized comparisons of conventional and minimally invasive approaches with regard to clinical outcome, complications, and cost. Position

• Supine with the arms positioned next to the body. • The patient may be temporarily placed in Trendelenburg at the time of de-airing of the ventricles before coming off bypass.

Incision

• Median sternotomy is the standard incision. • Alternative incision sites (e.g., via a right mini-thoracotomy) are used as part of “minimally

invasive mitral valve surgery.”

Approximate Time

Time typically varies between 4–8 hours depending on the experience of the team, the type of approach (standard versus minimally invasive approach), and technical difficulties. EBL Expected

• Cardiopulmonary bypass machine leads to dilution. • Blood loss typically ranges between 1,000–2,000 cc.

Hospital Stay

Surgical intensive care unit for 1–3 days; 7–10 days total in the hospital. Special Equipment for Surgery

• Cardiopulmonary bypass machine (operated by a perfusionist). • Standard equipment for open heart surgery. • Minimally invasive approaches require special equipment. • Transesophageal echocardiography probe (intraoperative examination performed by echotrained anesthesiologists or cardiologists).

EPIDEMIOLOGY Incidence N/A

Prevalence

About 65,000 MV repairs and replacements are performed in the US each year. Morbidity

• Bleeding, reoperation, stroke, renal failure, prolonged ventilation, and infection are known complications. • The incidence varies depending on preoperative status, length, and type of operation. • The 2008 ACC/AHA valvular disease guidelines refer to risk stratification models to estimate the risk of in-hospital mortality and morbidity of valve surgery with or without coronary artery bypass surgery (2)[B]. – US based registry by the Society of Thoracic Surgeons (STS) (3)[B]. Includes data from nearly 90% of cardiac surgery providers in the US and may provide the most accurate risk stratification for valve replacement. – European system for cardiac operative risk evaluation (“Euro Score”) – Scoring system developed from Great Britain’s and Ireland’s national data base

Mortality

• Varies significantly with age, co-morbidities, type of valvular lesion, ventricular function, concomitant valvular surgery, and/or bypass surgery. • Risk stratification models are useful to predict mortality risk for the individual patient (see under morbidity).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Hemodynamic stability throughout the induction period until initiation of bypass. Management depends on the type of lesion (stenosis versus regurgitation), right and left ventricular functions, pulmonary pressures, and other clinical factors. • After successful repair/replacement and completion of bypass, the goal is to maintain adequate cardiac output and blood pressure. Inotropes may be required if the left ventricular function is depressed.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Symptoms vary depending on the type of lesion (stenosis versus regurgitation) and the time course (acute versus chronic). • Chronic mitral regurgitation often remains asymptomatic for years. • Typical symptoms include shortness of breath, fatigue, palpitations, and heart murmur.

History

• See chapters on mitral stenosis, regurgitation, and prolapse. • Determine if there is a history of esophageal strictures or other abnormality that would prohibit placement of a transesophageal echocardiography probe during the procedure.

Signs/Physical Exam

Detailed description available in chapters on MV regurgitation, MV stenosis, and MV prolapse. MEDICATIONS

• Medical management depends on the type of lesion and other co-morbidities. • Initiation of statins may reduce the incidence of atrial fibrillation and mortality.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Preoperatively, a transthoracic echocardiography and sometimes a transesophageal echocardiography are obtained. • Coronary angiography is also routinely performed to determine whether the patient requires concurrent coronary bypass grafting.

CONCOMITANT ORGAN DYSFUNCTION

• Pre-existing renal dysfunction is of concern since further deterioration may be precipitated by catheterization prior to the valve replacement and by prolonged pump times. • Chronic pulmonary disease may worsen acutely secondary to bypass and lead to hypoxemia when coming off bypass. • Pre-existing neurologic deficits put the patient at great risk for further deterioration postoperatively.

TREATMENT PREOPERATIVE PREPARATION Premedications

Consider gentle anxiolysis with benzodiazepines. Special Concerns for Informed Consent

Morbidity and mortality risks vary with the extent of surgery (e.g., coronary bypass surgery in addition to valve replacement) and preexisting comorbidities. Antibiotics/Common Organisms

Skin flora is the greatest concern. Cefazolin may be utilized within 60 minutes prior to incision if the patient is not a carrier of multi-resistant bacteria and does not have an allergy; repeat every 3–4 hours until chest closure. Alternatively, vancomycin may be considered. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia in the US. • There are case reports of open heart surgery performed under epidural with sedation in other parts of the world. Monitors

• ASA standard monitoring. • Arterial line, most often, placed prior to induction; non-pulsatile flow during bypass does not allow for accurate non-invasive blood pressure measurement. • Central venous access is usually obtained after induction; pulmonary artery catheter placement may be considered. • Transesophageal echocardiography is frequently used intraoperatively to guide and assess MV repair/replacement. Induction/Airway Management

• The goal is to provide hemodynamic stability throughout the induction period; gentle administration of propofol with pressors or etomidate is most often used in combination with fentanyl. • Mask ventilation prior to endotracheal tube placement is performed except in cases of increased aspiration risk when a rapid-sequence induction is chosen. Maintenance

• Patients are usually maintained with oxygen/volatile agents and intermittent doses of opioids and non-depolarizing muscle relaxants. • During bypass, a volatile agent is added to the blood by the perfusionist through the bypass machine. • The management of patients during bypass varies substantially by institution and practitioner.

• On bypass, the target mean arterial blood pressure is typically between 50–80 mm Hg. • On bypass, the patient’s body temperature is cooled at the beginning and warmed to normal body temperature before the termination of bypass.

Extubation/Emergence

• Patients remain intubated and are transferred to the intensive care unit. • Postoperative sedation is typically provided with propofol infusion or most recently with dexmedetomidine infusion. The latter appears to have a lower risk for the development of postoperative delirium.

POSTOPERATIVE CARE BED ACUITY

• Surgical intensive care unit. • The time to extubation varies from a few hours to 24 hours. However, it can be several days depending on the patient’s hemodynamic status, respiratory status, bleeding/coagulation, and other organ systems.

ANALGESIA

• Analgesia is usually provided by intravenous opioids either as intermittent boluses or as continuous infusion until extubation. • Once the patient is extubated and the bowel function has returned, oral opioids can be given.

COMPLICATIONS

• Atrial fibrillation: Patients often present preoperatively but also have a high risk of developing it intraoperatively or postoperatively. • Replacement of a diseased heart valve with a prosthetic valve exchanges the native disease for complications that are unique to the prosthetic valve (3)[A]. A variety of complications can occur: – Structural failure (not uncommon with bioprosthesis, very rare with mechanical valve). – Severe and recurrent bleeding due to anticoagulant therapy. Note: Mechanical valves require long-term anticoagulation therapy, most often with warfarin, while patients with bioprosthetic valves usually receive anticoagulation with warfarin only for 6 weeks to 3 months postoperatively and then aspirin life-long. – Valvular thrombosis and thromboembolic events, especially in patients with mechanical valves and inadequate anticoagulant therapy. – Severe hemolysis mostly in mechanical valves. – Endocarditis. • Complications associated with open heart surgery and cardiopulmonary bypass (see chapter Cardiopulmonary Bypass).

PROGNOSIS

As survival after a first valve replacement has improved, more patients require a second operation for replacement.

REFERENCES

1. Bonow RO, Carabello BA, Chatterjee K, et al. Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2008;118:e523–e661. Vahanian A, Baumgartner H, Bax J, et al. Guidelines on the management of valvular heart disease: The task force on the management of valvular heart disease of the European Society of Cardiology. Eur Heart J. 2007;28:230–268. 2. Ruel M, Chan V, Bedard P, et al. Very long-term survival implications of heart valve replacement with tissue versus mechanical prostheses in adults <60 years of age. Circulation. 2007;116:I294–I300. Bolman RM, 3rd. Survival after mitral valve replacement: Does the valve type and/or size make a difference? Circulation. 2007;115:1336–1338. 3. Salem DN, O’Gara PT, Madias C, et al. American College of Chest Physicians. Valvular and structural heart disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:593S. • www.sts.org/quality-research-patient-safety/quality/risk-calculator-and-models/riskcalculator • www.euroscore.org • www.ucl.ac.uk/research/riskmodel/index.html See Also (Topic, Algorithm, Electronic Media Element) • Mitral regurgitation • Mitral stenosis • Mitral valve prolapse • Cardiopulmonary bypass

CODES ICD9 • V42.2 Heart valve replaced by transplant • V43.3 Heart valve replaced by other means ICD10 • Z95.2 Presence of prosthetic heart valve • Z95.4 Presence of other heart-valve replacement

CLINICAL PEARLS

• Mitral valve repair is preferred over replacement when feasible. • Risk stratification models are useful to predict morbidity and mortality risks for the individual patient. • Replacement of a diseased heart valve with a prosthetic valve exchanges the native disease for complications that are unique to the prosthetic valve.

• There is a significant rate of structural failure of bioprosthetic valves within the first 10–15 years, requiring reoperation.

MIXED VENOUS OXYGEN SATURATION (MVO2) Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Mixed venous oxygen saturation (MvO2) is the measurement of oxygen remaining in the

blood after passing through the body’s tissue capillary beds; it measures what is not used. • A true “mixed” venous sampling is taken from the distal port of the pulmonary artery catheter; it is comprised of blood from the superior and inferior vena cava and coronary sinuses. • MvO2 is the product of the starting arterial blood oxygen, how efficiently oxygen is transported or delivered throughout the body, and the amount of oxygen used by the body. Because oxygen delivery is dependent upon cardiac output (CO), hemoglobin (Hg), and oxygen saturation (O2 sat%), MvO2 can also serve as a surrogate to assess these factors. In

addition, it reflects dynamic functioning of the pulmonary and cardiac systems. • Whereas blood pressure, O2 sat%, and other monitoring tools provide information about

large scale circulation, MvO2 is one of the clinician’s (limited) resources to assess the

efficacy of the microcirculation and cell oxygenation.

PHYSIOLOGY PRINCIPLES

• (O2 starting) – (O2 consumed) = O2 remaining. MvO2 represents the unused O2 returning to the heart by modification of the Fick principle. • MvO2, or the O2 remaining in venous blood after perfusing the body, can serve as an

indicator of oxygen supply (O2 sat%, Hg, CO), oxygen demand (metabolic requirements of

tissues/cells), and tissue oxygenation (efficacy of O2 delivery to the demand).

• Under normal, resting conditions, MvO2 = 75% (PaO2 of 40 mm Hg). O2 supply >O2

demand, with only 25% of O2 utilized or extracted from the blood, which leaves a safety

reserve of 75%. • Train station analogy: O2 (cargo) is delivered to the lungs (train station) from the

atmosphere. O2 (cargo) is uploaded by the blood (train) that passes by, onto Hg molecules (boxcars). The heart pump (engine) delivers the oxygenated blood/oxyhemoglobin (cargofilled boxcars) to the tissues/cells (towns). The Hg (boxcars) is loaded to capacity with the O2 (cargo) at the lungs (train station) and the blood (train) returns unused O2 (cargo) to the lungs (train station). Because there is no reliable method to calculate all the O2 (cargo) that

is utilized by the tissues/cells (towns), it is indirectly determined by how much is loaded onto the blood (train) and what is returned. Under normal conditions, the cells/tissues

(towns) utilize approximately 25% of what is loaded at the lungs (train station); thus 75% of the Hg (boxcars) capacity returns to the lungs (train station). • Oxygen demand: Describes the amount of O2 necessary to satisfy the body’s metabolic requirements. O2 is required at the cellular level to maintain normal cell function and the

basal metabolic rate of each organ differs. In addition, it is dependent on factors such as temperature, metabolic conditions, and muscle work. Direct measurement is difficult, but by applying the Fick principle, it can be assessed indirectly by measuring the O2 consumption

(MvO2).

• Oxygen consumption: Describes the amount of O2 used by the tissues, and is equal to the O2

demand in the healthy patient. When demand increases (increased metabolic requirement), the body compensates by increasing CO (SV, HR) or O2 extraction in order to avoid

tissue/cellular hypoxia. • Oxygen supply: Because the body cannot store O2 (unlike glucose), its supply is entirely dependent on the dynamic and sustained function of the pulmonary (O2 sat%) and

circulatory (Hg, CO) systems. – Pulmonary: With inspiration, the patient receives an FIO2 of 21%, resulting in an alveolar

partial pressure (FA) of 100 mm Hg. FA = (Pbaro – PH20) (FIO2) – (PaCO2/0.8) = (760 –

47)(0.21) – (40/0.8) = 100 mm Hg. Because the capillary venous blood lacing/enveloping the alveoli has a PaO2 of 40 mm Hg (aka MvO2), a pressure gradient

exists that allows for simple diffusion from a higher to lower partial pressure (alveoli to capillary venous). – Blood oxygen content: The O2 from the alveoli is transported in the blood in two forms: Dissolved in plasma (2%) and attached to Hg (98%). O2 blood content = O2 dissolved + O2

bound to Hg = PaO2(0.003) + Hg(1.39)(SaO2). Under normal conditions, a Hg molecule

becomes completely saturated after traversing the alveoli. – Cardiovascular: The heart provides the pumping force that delivers the oxygenated blood to the tissues where it is consumed. Arterial blood oxygen content multiplied by CO equals O2 delivery. [(Hg)(1.39)(SaO2) + PaO2(0.003)] * CO * 10. An abnormality in any of these factors can result in reduced O2 delivery.

ANATOMY

• A true mixed venous sample is taken at the pulmonary artery (distal tip of pulmonary artery catheter). This allows for adequate mixing of blood from the superior vena cava (SVC), inferior vena cava (IVC), and coronary sinus. Technology for continuous monitoring of MvO2 has been developed and is built into special pulmonary artery catheters (precludes aspirating and sending samples). • At rest, venous return from the SVC (brain, heart), has a lower saturation (more tissue consumption) than from the IVC (lower extremities). • Whether SVC O2 sat% (ScO2) can be utilized to monitor global tissue hypoxia is a matter of

controversy. The benefit of ScO2 is that it can be attained from an upper body central

venous line sample, which is less invasive and may already be in place; in addition, it may allow a surrogate assessment of CO. Technology for continuous monitoring has been developed in special central line catheters (1). • If the PAC is wedged or partially wedged, the sample will reflect the composition of arterial blood. • A left-to-right intracardiac shunt (e.g., ventricular septal defect), results in “arterialized” blood, causing a “step up” in the saturation of the MvO2 as it passes through the right ventricle.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Pathophysiologic states can result in O2 demand > O2 delivered. An increase in demand

(increased metabolic requirement) is met by an increase in CO (increased HR, SV) or oxygen extraction (75% reserve). However, after the compensatory mechanisms are exhausted, demand > consumption, the tissue/cell resorts to anaerobic metabolism (without oxygen) in order to maintain cellular function. • Low MvO2 states: Potential increase in O2 demand/consumption, or reduced CO, Hg, or arterial saturation – Increased O2 demand/consumption: Fevers, seizures, shivering, fighting ventilator,

malignant hyperthermia, thyroid storm. If the patient has adequate cardiac reserve, the body will compensate by increasing CO, to preserve tissue oxygenation. With increasing demand above that, the body will compensate by increasing O2 extraction from the

arterial blood. – Reduced CO: Ischemia, infarction, negative inotropes, increased afterload, acute failure, reduced SV or hypovolemia, shock, arrhythmias, tamponade. When this occurs, the only available mechanism is to increase O2 extraction. Poorly tolerated compared to other causes of reduced MvO2.

– Reduced Hg: Hemorrhage, anemia, surreptitious blood loss. Mild reductions can often be met by increased CO in a patient with adequate cardiac reserve. Significant blood loss is met by an increase in CO and O2 extraction from the arterial blood. If the patient has

reduced cardiac reserve, they are at risk of tissue/cell hypoxia. – Arterial desaturation: Atelectasis causing reduction in FRC from positioning, insufflations, fluid overload, retractors, or other V/Q mismatch such as pulmonary embolism. Met by increased CO, followed by O2 extraction and does not necessarily result in anaerobic

metabolism or lactic acidosis if compensated for. • High MvO2 states: Potential reduced O2 demand/consumption, increased O2 sat%, Hg, or CO; arterialized venous sample. – Reduced O2 demand/consumption: Hypothermia, anesthesia, pharmacologic paralysis.

– Sepsis results in inappropriate shunting of blood away from cells/tissues that need O2, leaving them poorly oxygenated and resorting to anaerobic metabolism. This is a maladaptation, given that the shunted blood returns to the heart highly oxygenated or

unused (increased MvO2) (2,3).

– AVMs and other large shunts can also create a similar clinical scenario (increased MvO2

despite oxygen deprivation, secondary to inappropriate shunting of blood away from tissues). – Cyanide poisoning prevents utilization of O2 at the cellular level because oxidative enzymes are blocked or only partially functional; prevents Hgb unloading from capillary blood. Blood returns highly oxygenated, (increased MvO2), despite cell hypoxia.

– Increased arterial saturation: Increased FIO2, increased FRC (alveolar recruitment from PEEP, larger tidal volumes, positioning such as reverse Trendelenburg, removal of abdominal retractors), improved V/Q matching. – Increased Hg: Blood transfusion. – Increased CO: Increased inotropy from medication, sympathetic stimulation, reduced afterload, increased preload (Starling curve), resolution of arrhythmia, increased heart rate (4). – A wedged PAC samples blood from surrounding alveoli that has been oxygenated; referred to as “arterialized” sample.

PERIOPERATIVE RELEVANCE

• When there is an imbalance of O2 supply to demand, the body mobilizes its compensatory mechanisms to ensure adequate availability; increased O2 extraction and CO.

• Intraoperatively, O2 is usually at steady state consumption, and a reduction should prompt a search for reduced tissue delivery, often from reduced CO, but also from low Hg or O2 sat%

(4). Reduced CO is problematic, as it removes one of the body’s compensatory mechanisms for tissue/cell oxygenation. • Studies have demonstrated that a decrease in MvO2 generally precedes or indicates

imminent cardiac failure (10–15 minutes prior) as well as poor overall prognosis. In addition, consequent lactic acidosis is presumptive evidence of tissue hypoxia and is also associated with a poor prognosis. • In the ICU, it can be utilized to monitor, assess, and guide therapy during sepsis. • ScVO2 may be utilized, as it is less invasive and is more routinely inserted in critically ill patients. Values should be evaluated with caution as it reflects the degree of O2 extraction

from the brain and upper body (1). • PAC migration often occurs in cardiac surgery when the heart is being manipulated. Deflate the balloon and pull the catheter back 1–3 cm.

EQUATIONS •

13.9 = K factor (derived from 1.39 × 10, see below) • MvO2 normal values: – Mixed venous oxygen saturation = 60–80%

– Mixed venous partial pressure = 35–45 mm Hg • Venous oxygen content; CvO2 = 15.5 mL/dL

– O2 dissolved + O2 bound to Hg {Hg × 1.39 × MvO2) + PvO2(0.003) = 15.5 mL/dL. – 1.39 = mL of O2 that can bind to 1 g of Hb

– 0.003 = solubility coefficient of O2 in plasma

– (15 × 1.39 × 0.75) + 40(0.003) = 15.5 mL/dL • Venous O2 transport = DvO2 = 775 mL O2/min. – CvO2 × CO × 10 = 775 mL O2/min

– 15.5 mL/dL × 5 L/min × 10 = 775 mL O2/min

– Multiplying by 10 allows to convert from dL to mL • Arterial oxygen content; CaO2 = 20.1 mL/dL – Arterial O2 Saturation = SaO2-95–98%

– Arterial O2 partial pressure = 80–100 mm Hg

– O2 dissolved + O2 bound to Hg

– [Hg × 1.39 × SaO2] + [PaO2(0.003)] = 20.1 mL/dL

– (15 × 1.39 × 0.97) + 100(0.003) = 20.1 mL/dL • Arterial O2 transport = DO2 = 1005 mL O2/min – CaO2 × CO × 10 = 1005 mL O2/min

– 20.1 mL/dL × 5 L/min × 10 = 1005 mL O2/min

• VO2 = Arterial O2 transport – Venous O2 transport – = (CO × CaO2 × 10) – (CO × CvO2 × 10)

– = CO (CaO2 – CvO2) × 10

– = CO × [(Hg × 1.39 × SaO2)−(Hg × 1.39 × SvO2)] ×10

– = CO × Hg ×1.39 × (SaO2−SvO2) × 10 – = CO × Hg × 13.9 × (SaO2 – SvO2)

– = (5 L/min × 15 g/dL × 13.9) × (0.97−0.75) – Note that the O2 dissolved in plasma is excluded because it is miniscule – = 230–250 mL O2/minute

– Extraction = 250/1005 mLO2 = 25%

REFERENCES

1. Ho KM, Harding R, Chamberlain J, Bulsara M. A comparison of central and mixed venous oxygen saturation in circulatory failure. J Cardiothoracic Vasc Anesth. 2010;24(3):434– 439. 2. Edwards JD. Oxygen transport in cardiogenic and septic shock. Crit Care Med. 1991;19(5):658–663.

3. Shoemaker WC, Appel PL, Kram HB, Bishop M, Abraham E. Hemodynamic and oxygen transport monitoring to titrate therapy in septic shock. New Horiz. 1993;1(1):145–159. 4. Cariou A, Monchi M, Dhainaut JF. Continuous cardiac output and mixed venous oxygen saturation monitoring. J Crit Care. 1998;13(4):198–213.

ADDITIONAL READING

• Kelly KM. Does increasing oxygen delivery improve outcome? Yes. Crit Care Med. 1996;12(3):635–644. • Yu M, Levy MM, Smith P, Takiguchi SA, Miyasaki A, Myers SA. Effect of maximizing oxygen delivery on morbidity and mortality in critically ill patients: A prospective, randomized controlled study. Crit Care Med. 1993;21(6):830–838.

See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary artery catheter • Cardiac output • Sepsis

CLINICAL PEARLS

• Mixed venous oxygenation saturation provides a measurement and tool to assess tissue oxygenation in the perioperative and intensive care unit period. Most of the current monitors of perfusion are on a global level. • The venous oxygen saturation is directly measured and inferences about the contributing factors can be made (hemoglobin levels, oxygen consumption, and cardiac output).

MULTIPLE MYELOMA Keyuri Popat, MD

BASICS DESCRIPTION

• Multiple myeloma describes the abnormal, excessive growth of a single clone of plasma cells with a resultant monoclonal immunoglobulinopathy. • These abnormal plasma cells grow in the bone marrow resulting in extensive skeletal destruction with osteolytic lesions, osteopenia, and/or pathologic fractures. • Patients with multiple myeloma may present for interventional pain therapy, spinal cord decompression, bone marrow transplant, pathological fracture repair, or other non-related procedures. EPIDEMIOLOGY Incidence

Approximately 1% of all cancers. Prevalence

• Approximately 10% of all hematologic malignancies • Age adjusted incidence has remained stable at 4 per 100,000 persons • Median age of onset 66 years • Men > women • African Americans > Caucasians

Morbidity

Incurable disease Mortality

Responsible for approximately 20% of deaths from hematologic malignancies; 2% of deaths from all cancers ETIOLOGY/RISK FACTORS

• First degree relatives have a 3.7-fold increase in incidence • More common in farmers, miners and those with wood dust exposure

PATHOPHYSIOLOGY

• Multiple myeloma is a clonal B cell malignancy. While some steps of replication of the malignant clone have been discovered, many remain unknown. Almost all myeloma cases are preceded by a premalignant plasma cell proliferative disorder known as monoclonal gammopathy of undertermined significance (MGUS). MGUS is present in over 30% of the population above the age of 50 years, and progresses to myeloma or a related malignancy at

a rate of 1% per year. • The disease is characterized by the aberrant expansion of plasma cells within the bone marrow as well as extramedullary sites. The most common sites are the back and chest; extramedullary plasmacytomas can be found in the oronasopharynx and paranasal sinuses and rarely throughout the gastrointestinal system, lung, and central nervous system. • Bone lesions: The abnormal proliferation of the plasma cell line results in overcrowding and encroachment of normal progenitor cells. This results in classic bone pain with lytic lesions that can present on routine skeletal films. • Hypercalcemia may be either symptomatic or discovered incidentally. This is due to increased bone resorption, which in turn is due to the release of osteoclast activating factors such as lymphotoxin, interleukin-6, hepatocyte growth factor, and receptor activator of nuclear factor kappa B ligand (RANK ligand). • Immune system: Patients with myeloma are prone to infection due to a combination of immune dysfunction and physical factors. Immune dysfunction results from impaired lymphocyte function, suppression of normal plasma cell function, and hypogammaglobulinemia (due to suppression of normal gamma globulin). Physical factors that predispose to pulmonary infection include hypoventilation secondary to pathologic fractures and pain involving the rib cage. • POEMS syndrome (osteosclerotic myeloma): Polyneuropathy, Organomegaly, Endocrinopathy (hypogonadism, adrenal insufficiency), Monoclonal protein, Skin changes is a rare presentation of monoclonal cell disorder due to chronic overproduction of proinflammatory and other cytokines (e.g., vascular endothelial growth factor). Microangiopathy, edema, effusions, increased vascular permeability, neovascularization, polyneuropathy, and pulmonary hypertension are also features of this syndrome.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assessment of concomitant organ dysfunction should be performed, with the anesthetic tailored as needed (e.g., renal disease requiring adjustments to medication doses). • Patients may have significant pain and be on chronic analgesia; appropriate pain management should be provided. • Careful patient positioning should be performed given the possibility of skeletal destruction, radiculopathy, and cord compression. • Macroglossia can result from amyloid deposition in approximately 15% of patients and may present difficulty with airway management.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Pain • Fatigue • Paralysis/paraparesis

History

• Bone pain

• Neuropathy secondary to chemotherapy • Thrombosis secondary to thalidomide • Renal failure • Anemia • Infection • Spinal cord compression

Signs/Physical Exam

• Fracture • Kyphosis • Motor and sensory neurologic deficit • Macroglossia

MEDICATIONS

• Thalidomide, bortezomib, and lenalidomide (are at higher risk for thrombosis and rarely of interstitial lung disease) • Vincristine, doxorubicin, and dexamethasone • Analgesics • Erythropoietin

TREATMENT • Stem cell transplantation • Blood, platelet, plasma transfusions • Plasma exchange (patient’s plasma is removed on a cell separator and replaced with transfusions of human albumin or synthetic plasma)

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, including calcium level • BUN/Creatinine • Complete blood count • Urinalysis for proteinuria: Plasma cell proliferation increases total serum proteins and results in “spillage” into the urine.

CONCOMITANT ORGAN DYSFUNCTION

• Nervous system: Most commonly includes radiculopathy and cord compression. This can occur due to direct plasma cell proliferation in the spinal cord or due to bone collapse. Rarely, peripheral neuropathy due to amyloidosis and central nervous system plasmacytoma is also seen. Hyperviscosity from monoclonal immunoglobulins may result in stroke or confusion. • Cardiovascular: Amyloid deposition can result in restrictive cardiomyopathy and reduce chamber filling and contractility, as well as cause capillary fragility. • Renal disease can be glomerular (amyloidosis, immunoglobulin deposition), tubular (cast

nephropathy), or interstitial (interstitial nephritis, plasma cell infiltration). This can be the presenting feature of myeloma. • Skeletal destruction commonly involves the spine and can cause vertebral collapse or cord compression. • Anemia is due to the involvement of the bone marrow which replaces normal hematopoietic tissue and by the disruption of the bone marrow microenvironment. • Airway: Macroglossia may result from amyloid deposition and can occur in 15% of patients. • Hypercoagulability occurs due to the disease itself, as well as from treatment with thalidomide. There is increased risk of both venous and arterial thrombosis.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Acute infection due to poor immunity as discussed above • Acute thrombosis • Need for plasmapheresis

CLASSIFICATIONS

• Based on bone marrow biopsy and cytogenetics. • Broadly classified as: – Monoclonal gammopathy of unknown origin (MUGUS); asymptomatic. – Multiple myeloma (MM): End organ damage maybe present. – Smoldering multiple myeloma (SMM); asymptomatic

TREATMENT PREOPERATIVE PREPARATION Premedications

Analgesics as needed; patients may have developed a tolerance and require higher dosages. INTRAOPERATIVE CARE Choice of Anesthesia

• General: Be aware of possible renal failure and thus the choice of agents used for induction and maintenance of anesthesia. Use of certain muscle relaxants cleared by the kidney may have a longer than desired duration of action. • Regional anesthesia as the sole technique or for postoperative pain may also be used. If a neuraxial technique is considered, evaluate the spine carefully for fractures and any anticoagulation issues that may contraindicate placement. • Thromboprophylaxis should be discussed with the surgeon and appropriately planned.

Monitors

• Standard ASA monitors • Consider arterial line placement in patients with concomitant organ failure

Induction/Airway Management

• Any neck manipulation should be done cautiously due to the possibility of lytic spine

lesions. • Macroglossia may make ventilation or intubation challenging. • Pharmacokinetics of anaesthetic drugs may be unpredictable due to an altered volume of distribution, drug clearance, and plasma albumin/globulin ratio. The possibilities of change in protein binding have been alluded to in the past but no studies have proven this to be clinically significant (3). Maintenance

• Analgesia may be challenging as patients may be on high dose or chronic narcotics. Requirements should be increased accordingly. • Adequate hydration is important to avoid the precipitation of hyperviscosity syndrome and renal failure. • Careful and meticulous positioning and padding of pressure points should be performed.

Extubation/Emergence

No special consideration; routine extubation criteria apply.

POSTOPERATIVE CARE BED ACUITY

• Consider supplemental oxygen (nasal cannula, face mask). • Pain management may be challenging in opioid tolerant patients; consider an acute pain consultation or the placement of regional/neuraxial blocks if appropriate.

COMPLICATIONS

• Inadequate analgesia • Fluid overload • Perioperative thrombosis

REFERENCES

1. Rajkumar SV. Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol. 2011;86(1):57–65. 2. Mahindra A, Hideshima T, Anderson KC. Multiple myeloma. Blood Rev. 2010;24(Suppl 1):S5–11. 3. Walder AD. Failure of anaesthesia with etomidate. Eur J Anaesthesiol. 1995;12(3):325– 327. 4. Dabrowska DM, Gore C, Griffiths S, et al. Anaesthetic management of a pregnant patient with multiple myeloma. Int J Obstet Anesth. 2010;19(3):336–339.

ADDITIONAL READING

• Falanga A, Marchetti M. Venous thromboembolism in the hematologic malignancies. J Clin Oncol. 2009;27(29):4848–4857.

See Also (Topic, Algorithm, Electronic Media Element)

• Bone marrow harvest • Intrarenal failure • Epidural hematoma • Vertebroplasty/kyphoplasty • Pulmonary embolism

CODES ICD9

• 203.00 Multiple myeloma, without mention of having achieved remission • 203.01 Multiple myeloma, in remission ICD10 • C90.00 Multiple myeloma not having achieved remission • C90.01 Multiple myeloma in remission

CLINICAL PEARLS

• Assess for the severity of disease in order to appropriately formulate an anesthetic plan. • Pain control may be a challenge due to multiple lytic lesions. Consider acute pain consult, regional block. • Adequate hydration can reduce the occurrence of hypercalcemia and possible renal damage. • Careful patient positioning to avoid nerve injury. • Rarely, abnormal pharmacokinetics may be present secondary to changes in the albumin/globulin ratio. • If a transfusion is needed or anticipated perioperatively, a discussion with the surgeon and possibly a hematologist should be conducted.

MULTIPLE SCLEROSIS

Christine E. Goepfert, MD, PhD, DESA

BASICS DESCRIPTION

• Multiple sclerosis (MS) is a polygenic, organ specific autoimmune disease of unknown etiology. There exist evidentiary signs of tissue destructive activity of humoral and/or cellular immune system in the myelin components of the central nervous system (CNS). • It was first described by Dr. J. M. Charcot (1825–1893) and named in accordance with the widespread “scars” seen in the CNS. • MS is the most common demyelinating disorder of the CNS and is the leading cause of acquired neurological disability in young adults. EPIDEMIOLOGY Incidence

Female > males in a 2.3:1 ratio. Prevalence

• In the US, it is present in 30–80 per 100,000 persons. • Peaks around the age of 30. • Regional differences exist. In the north–south gradient, there is a higher risk in northern, industrialized countries. It is rare in Asians and Africans. • There appears to be a genetic component, with a 10- to 50-fold greater occurrence in relatives of MS patients. Morbidity

In 20–40% of patients, it is considered benign with minimal permanent disability Mortality

• Survival is linked to the extent of disability/secondary complications (lungs, renal). • Life-expectancy is slightly shortened in most patients. • Higher risk for suicide.

ETIOLOGY/RISK FACTORS

• Complex interaction of genetic and environmental factors: Related to certain HLA types and over-expression of human endogenous retroviruses (HERVs), resulting in an altered immune response. • Multiple genetic loci have been identified; however, the penetrance of risk only has a maximum of 25%. • Involvement of infectious factors include: Viruses (EBV, HHV-6), hepatitis B vaccination, chlamydia pneumonia.

• Hygiene related factors, low levels of vitamin D, production of melanoma-like melanin.

DISEASE/PATHOPHYSIOLOGY

• MS is a neurodegenerative, primary inflammatory disease that affects both white and gray matter. It is classically considered a disease of demyelination; however, histopathology also demonstrates neuroaxonal damage. • There is a proliferation of CD4 helper T-cells with the formation of cytokines resulting in blood brain barrier (BBB) damage, production of antibodies, and perforins. • Exacerbations are dependent on oxidative/nitrosative stress mitochondrial alterations, and stressful life-events.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Decrease perioperative stress and maintain body homeostasis to avoid exacerbations. • The response to non-depolarizing muscle relaxants is variable. Succinylcholine should be avoided. • Medications for the treatment of multiple sclerosis may result in co-morbidites with anesthetic implications as well as interactions with anesthetic medications.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Depression • Paresthesias • Paresis • Ataxia, dystonia, vertigo (cerebellar symptoms) • Pain (in 30–50%): Neuropathic and neurogenic pain, trigeminal neuralgia • Chronic fatigue (>75%), emotional changes

History

• Remissions and relapses: Determine course of disease and neurological function. • Determine the effects of heat • Determine if there are side effects of therapies

Signs/Physical Exam

• Nystagmus • Spasticity with dysfunctional reflexes • Muscle atrophy • Respiratory distress, use of accessory muscles, small tidal volumes, one-sided diaphragm impairment • Hypotonia, bradycardia (autonomic nervous system)

TREATMENT HISTORY

• Stem cell transplantation • Plasmapheresis

MEDICATIONS

• General principle: Anti-inflammatory and neuroprotective therapy targeting neuronal processes and cell bodies. • Medications for the prevention of relapse: – First-line treatment: Interferon-β1α: May be administered IM or SC depending on the formulation. Can result in hepatic failure/elevated LFTs, leukopenia. Glatiramer acetate can result in a self-limited, post-injection systemic reaction with chest tightness, flushing, anxiety, dyspnea, and palpitations in 15% of patients. This may be mistaken for cardiac ischemia or hives. – Second-line agents: Mitoxantrone is an immunosuppressive, chemotherapeutic agent. May result in AML, leukopenia, congestive heart failure and decreased LVEF, nausea/vomiting. Natalizumab is a specific mAb. Side-effects include infections (e.g., UTIs, URIs), arthralgias. Fingolimod is an immunomodulator. • Medications for exacerbation: – High dose methylprednisolone (5–15 mg/kg/d for3–10 days). – Immunosuppressants: Azathioprine, cyclophosphamide • Symptom-oriented medication – Baclofen for spasticity (intrathecal, oral) – Amantadine for fatigue – Antidepressants for depression – Carbamazepine and phenytoin for pain syndromes – Anticholinergics for neurogenic bladder

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• When significant respiratory insufficiency is present, consider pulmonary function testing and an arterial blood gas. • Imaging studies: MS is primarily a clinical diagnosis. An MRI (T2-weighted) can show multifocal lesions involving periventricular white matter, optic nerve, brainstem, and spinal cord white matter. • CSF analysis: Intrathecal IgG synthesis and oligoclonal bands with lymphocytic pleocytosis. • Evoked potentials: Visual evoked potentials (VEP) and somatosensory evoked potentials (SSEPs). • Plasma: Endothelial microparticles.

CONCOMITANT ORGAN DYSFUNCTION

• Depression, emotional changes, optic neuritis (70%), nystagmus, paresthesias, spasticity with dysfunctional reflexes, and atrophy. Cerebellar symptoms include ataxia, dystonia, and vertigo. • Autonomic nervous system dysfunction may manifest as hypotonia or bradycardia. • Respiratory: Muscle weakness can result in a decreased FRC, as well as maximal inspiratory

and expiratory efforts. Diaphragmatic palsy may be seen in cervical cord involvement. If central control of ventilation is impaired, there may be a decreased response to PaCO2.

• Pain (in 30–50%): neuropathic and neurogenic pain, trigeminal neuralgia. • Chronic fatigue (>75%) • GERD

CIRCUMSTANCES TO DELAY/CONDITIONS • Current exacerbation • Acute cardiotoxic effects of mitoxantrone

CLASSIFICATIONS

• McDonald criteria: Diagnostic criteria with clinical findings to prove dissemination in time and space of lesions supported by MRI, VEP, and CSF • Relapsing-remitting (RRMS): 80% • Secondary progressive (SPMS): 50% of RRMS after 10–15 years • Primary progressive (PPMS): 15% and carries the worst prognosis • Progressive relapsing (PRMS): 5%

TREATMENT PREOPERATIVE PREPARATION Premedications

• Consider high-dose glucocorticoids above the antiemetic dose after discussion with a neurologist. • In patients with respiratory dysfunction at baseline, benzodiazepines and opioids should be cautiously titrated if needed. Patients should be monitored with pulse oximetry. Special Concerns for Informed Consent

• Patients should be informed about the potential for postoperative exacerbations. • Depression might make informed consent difficult. • Pregnancy may cause partial remission; however, in the postpartum period, there is an increased risk of exacerbation. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia is considered safe. • Regional anesthesia is possible after carefully weighing the risks and benefits. – Respiratory dysfunction may be decreased. Avoid intubation, ventilation, and sedation; beneficial in patients with central nerve involvement or respiratory muscle weakness. – “Double-crush” phenomenon due to involvement of the peripheral nervous system, which may be subclinical. Peripheral nerve damage has been reported after peripheral nerve blocks. – Epidural anesthesia may be preferred over spinal anesthesia, which is associated with

exacerbations as well as profound hypotension that is resistant to vasopressors. – Because neurons are demyelinated, they may be more susceptible to local anesthetic neurotoxicity, which can aggravate conduction blockade. To that extent, consider lower concentrations and decreased exposure.

Monitors

• Standard ASA monitors; careful attention to temperature • Neuromuscular monitoring when neuromuscular blocking agents are utilized

Induction/Airway Management

• Good pre-oxygenation • Consider a rapid sequence induction if the patient has dysphagia. There is an increased risk of aspiration if the cranial nerves are involved (decrease in pharyngeal and laryngeal reflexes). However, avoid succinylcholine, because up-regulation of acetylcholine (ACh) receptors may lead to hyperkalemia. The response to non-depolarizing drugs is variable. The patient may be resistant due to upregulation of ACh receptors or co-medication with anticonvulsants. However, muscle atrophy and baclofen can render the patient more sensitive to its effects.

Maintenance

• No studies exist that demonstrate a benefit with any particular technique. However, inhalational agents have been shown to increase the risk of hypotension due to defects in the autonomic nervous system. • Maintain at a “deep” level of anesthesia to avoid stress (MAC-BAR). • Neuromuscular blockade has an unpredictable response. Utilization of a nerve stimulator can aid with dosing • Temperature: Meticulously avoid increases in body temperature as this can slow nerve conduction in demyelinated nerves.

Extubation/Emergence

• Goals include reducing stress/distress while ensuring sufficient respiratory function. • Consider administering pre-emptive analgesia to minimize postoperative pain (needs to be balanced against its respiratory effects).

POSTOPERATIVE CARE BED ACUITY

Depends on the surgery and baseline condition. The patient should be placed in an ICU if they have respiratory muscle weakness, diaphragmatic palsy and hypoventilation, or dysphagia due to cranial nerve involvement. MEDICATIONS/LAB STUDIES/CONSULTS

Neurological assessment by the anesthesia team, and in the event of any uncertainties, by a formal neurologic consult. COMPLICATIONS

• Respiratory failure/aspiration • Exacerbations of MS, primarily due to inappropriate pain management, hyperthermia, and psychological distress • Potential drug interactions of anesthetics with immunosuppressants, antispasticity and antiepileptic drugs, and anticholinergics

REFERENCES

1. Dickerman RD, Schneider SJ, Stevens QE, et al. Prophylaxis to avert exacerbation/relapse of multiple sclerosis in affected patients undergoing surgery. Surgical observations and recommendations. J Neurosurg Sci. 2004;48(3):135–137.

2. Dorotta IR, Schubert A. Multiple sclerosis and anesthetic implications. Curr Opin Anaesthesiol. 2002;15:365–370.

3. Koff MD, Kohen JA, McIntyre JJ, et al. Severe brachial plexopathy after an ultrasoundguided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis. Anesthesiology. 2008;108(2):325–328. 4. Krone B, Grange JM. Paradigms in multiple sclerosis: Time for a change, time for a unifying concept. Inflammopharmacology. 2011;19(4):187–195. 5. Stadelmann C. Multiple sclerosis as a neurodegenerative disease: Pathology, mechanisms and therapeutic implications. Curr Opin Neurol. 2011;24:224–229. 6. Vercauteren M, Heytens L. Anaesthetic considerations for patients with pre-existing neurological deficit: Are neuroaxial techniques safe? Acta Anaesthesiol Scand. 2007;51(7):831–838. See Also (Topic, Algorithm, Electronic Media Element)

• Postoperative pulmonary complications • Epidural

CODES ICD9 340 Multiple sclerosis ICD10 G35 Multiple sclerosis

CLINICAL PEARLS

• The primary goal is to avoid any perioperative stress, especially hyperthermia. • Monitor neuromuscular blockade closely or consider alternatives such as topicalization with lidocaine or deep anesthesia with remifentanil. • Interestingly, in patients with MS, there are no exacerbations seen during pregnancy. However, there is a threefold increase in exacerbations postpartum; this is independent of whether the patient had anesthesia or not. It may be explained by infection, emotional

lability, and hyperpyrexia.

MYASTHENIA GRAVIS Fabrizio Racca, MD Elena C. Capello, MD Federica Manfroi, MD V. Marco Ranieri, MD

BASICS DESCRIPTION

• Myasthenia gravis (MG) is an autoimmune postsynaptic neuromuscular junction (NMJ) transmission disorder. In the majority of cases (85%), MG is associated with auto-antibodies against the acetylcholine (ACh) receptor. • The hallmark of the disorder is weakness and fatigability in ocular, bulbar, limb, and respiratory muscles. EPIDEMIOLOGY Prevalence

In the US, 10–20 new cases of MG per million annually Prevalence

• In the US, 150–200 cases of MG per million population • Bimodal distribution of MG tending to affect: – Young woman: 20–40 years of age – Older men: 50–70 years of age Morbidity

• Intermittent impairment of muscle strength, which may cause aspiration and increased incidence of pneumonia and falls. • Medications used to control the disease may produce adverse effects.

Mortality

• In the past, untreated MG had a mortality rate of 30–70%; now most patients have a nearnormal life expectancy. • Myasthenic crisis: Even with prompt diagnosis and treatment, the mortality rate of a myasthenic crisis is <5%. ETIOLOGY/RISK FACTORS

• Cause remains unknown. It is an autoimmune disorder and does not appear to have a genetic predisposition. In some cases, it may be associated with a thymoma or other autoimmune disorders. • Myasthenic crisis: – Infection

– Hypothermia – Hypokalemia, hypophosphatemia – Surgical intervention – Pregnancy, childbirth – Tapering of immunosuppressive medications – Drugs that may worsen the muscular weakness: Aminoglycosides, fluoroquinolones, macrolides, beta-blockers, diuretics, procainamide, magnesium salts, calcium channel blockers, intravenous iodinated contrast agents, glucocorticoids

PHYSIOLOGY/PATHOPHYSIOLOGY

• Normal muscle contraction is the result of pre-synaptic release of ACh into the NMJ. ACh binds to acetylcholine receptors (AChR) on the postjunctional membrane; when both α subunits of the AChR are bound, it undergoes a conformational change that allows sodium and calcium to flow intracellularly and increase the voltage (make positive). The membrane resting potential is ∼−90 mV, and when a membrane threshold of −30 mV is attained (∼10–20% of AChR are opened), voltage-gated ion channels open and fully depolarize the membrane, producing an action potential. • MG is the result of an antibody-mediated attack against ACh postsynaptic receptors of the NMJ, leading to a reduction in the number of ACh receptors. Consequently, there is a decrease in the agonist effect of ACh on the postsynaptic NMJ; therefore, the membrane threshold is less easily attained. • This results in a characteristic pattern of progressively reduced muscle strength with repeated use of the muscle and recovery of muscle strength following a period of rest. • Myasthenic crisis is an exacerbation and can result in a life-threatening condition, characterized by neuromuscular respiratory failure. Severe bulbar muscle weakness often accompanies the respiratory muscle weakness or may be the predominant feature. Myasthenic crisis may be precipitated by a variety of factors (see Risk Factors). In addition, it can occur spontaneously as part of the natural history of MG itself. • Cholinergic crisis results from an excess of anticholinesterase drugs. Excessive ACh stimulation produces flaccid muscle paralysis and pupil constriction.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess the severity of disease, evaluate pulmonary function, and optimize medications. • Continue anticholinesterase drugs in the preoperative period. In the postoperative period, anticholinesterase drugs should be administered slowly and cautiously. Patients may have a decreased requirement of these drugs in the first 48 hours. • Avoid muscle relaxants in MG patients, if possible. MG patients have an abnormal response to depolarizing (i.e., relative resistance) and non-depolarizing (i.e., more prolonged action) blocking agents. • The anesthetic plan should consider the use of ultra-short–acting anesthetics in order to avoid postoperative respiratory depression and hypoventilation. • Avoid postoperative mechanical ventilation (MV), whenever possible. Most patients may be safely extubated at the end of the procedure, but those with severe MG may benefit from a period of MV.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Fatigable weakness that worsens after exercise and improves with rest • Chronic, fixed weakness may also be present

History

• Age of onset • Clinical course – Early in MG, the symptoms may be absent upon awakening – Often as the disease progresses, the symptom-free periods are lost; symptoms are continuously present but fluctuate from mild to severe. • Treatment history • Hospitalizations • Intubations and ICU admissions

Signs/Physical Exam

• Ptosis and/or diplopia (>50% of patients with MG) • Bulbar symptoms including dysarthria, dysphagia, fatigable chewing (about 15% of patients with MG) • Proximal limb weakness • Facial muscles are frequently involved and make the patient appear expressionless • On physical examination, the findings are limited to the motor system, without loss of reflexes or alteration of sensation or coordination. • Careful assessment of respiratory function, ability to cough, and bulbar function

MEDICATIONS

Evaluate the adequacy of drug therapy • Anticholinesterases • Immune suppression (steroids, azathioprine, cyclosporine) • Thymectomy (for patients with generalized MG with thymoma or who are less than age 60 without thymoma) • Plasmapheresis and intravenous immune globulin. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Pulmonary function tests (negative inspiratory pressure and forced vital capacity) • Arterial blood gasses (ABGs): The paCO2 and paO2 can help to predict the need for postoperative MV. • Chest x-ray may be indicated to rule out aspiration or other pneumonias.

CONCOMITANT ORGAN DYSFUNCTION

• Thymoma: The majority of patients with AChR antibody-positive MG have thymic abnormalities; hyperplasia in 60–70% and thymoma in 10–15%.

• Other autoimmune disorders that may be present include systemic lupus erythematous, rheumatoid arthritis, pernicious anemia, thyrotoxicosis.

CIRCUMSTANCES TO DELAY/CONDITIONS THAT NEED OPTIMIZATION

If the patient is poorly controlled, a course of plasmapheresis may be of benefit in the preoperative period. There should a 24-hour delay between the last plasmapheresis and surgery to restore clotting factors. CLASSIFICATIONS

• Grades – Grade I: Only eyes affected – Grade IIa: Mild generalized MG responding well to therapy – Grade IIb: Moderate generalized MG responding less well – Grade III: Severe generalized disease – Grade IV: Myasthenic crisis requiring MV • Preoperative factors associated with need for prolonged postoperative MV include: FVC <2.9 L, history of MG >6 years, major surgery, co-existing lung disease, and grades III and IV MG

TREATMENT PREOPERATIVE PREPARATION Premedications

• Continue all the doses of medications preoperatively to avoid aggravation of symptoms and muscle weakness. • Steroid-dependent patients will require steroid stress dose (hydrocortisone up to 100 mg IV bolus before induction, then 100 mg q8h × 24h). • Avoid sedatives as they can cause respiratory compromise.

Special Concerns for Informed Consent

Inform the patient of the potential requirement for prolonged MV. INTRAOPERATIVE CARE Choice of Anesthesia

• Use of regional or local anesthesia should be utilized, whenever possible. • Since local anesthetic agents may block neuromuscular transmission, it is better to use techniques which involve the use of small quantities of these agents; therefore, subarachnoid block is preferable to the use of epidural or caudal anesthesia. Monitors

• Standard ASA monitors • Consider an arterial line in high-risk patients and for thymectomy (ABGs, electrolyte analysis, and invasive arterial pressure monitoring): Monitoring of neuromuscular transmission (nerve stimulator).

Induction/Airway Management

• Airway should be secured with an appropriate size ET tube using a non-paralyzing technique. Sevoflurane often provides adequate relaxation for tracheal intubation. • When muscle relaxant use is indicated, it is better to use small doses (1/10th of the usual dose) of non-depolarizing rather than depolarizing relaxant drugs. • The presence of a thymoma (anterior mediastinal mass) can result in intrathoracic airway or vascular obstruction and may occur upon the induction of anesthesia.

Maintenance

• Several general anesthetic techniques have been proposed (balanced anesthetic technique or TIVA), although none has been proven to be superior to the other. • Avoid muscle relaxants, if possible. Volatile anesthetics may provide adequate relaxation during surgery; however, intermediate and short-acting non-depolarizing agents can be used. It is best to use small doses with careful monitoring of neuromuscular transmission. • Preferentially utilize ultra-short–acting anesthetics (propofol, sevoflurane, remifentanil). • Avoid factors which can enhance neuromuscular blockade (hypothermia, hypokalemia, hypophosphatemia, and certain drugs).

Extubation/Emergence

• Criteria for extubation include: – Head lift (5 sec) – Negative inspiratory force of >25 cm of H2O

– Tidal volume >5 mL/kg – Adequate muscle power evidenced by nerve stimulator • Adequate postoperative pain control, pulmonary toilet, and the avoidance of drugs that interfere with neuromuscular transmission facilitate tracheal extubation. • Anticholinesterases therapy should be restarted in the immediate postoperative period. The dose is based on the preoperative pyridostigmine dose (2 mg IV neostigmine is equivalent to 60 mg PO pyridostigmine) and titrated to effect.

FOLLOW-UP BED ACUITY

• Postoperative care should take place in the ICU with monitoring of respiratory function as well as chest physiotherapy for 12 hours. • Meticulous attention to pulmonary toilet is required, particularly since respiratory secretions may be increased by anticholinesterase drugs • Good pain control, especially after thymectomy • Avoid drugs that may exacerbate MG.

COMPLICATIONS

• Weakness after surgery presents a special problem in MG patients. The differential diagnosis includes myasthenic crisis, residual effects of anesthetic drugs, non-anesthetic drugs interfering with neuromuscular transmission, and cholinergic crisis. For these reasons, many

clinicians prefer to avoid the use of muscle relaxants, or if they use muscle relaxants, allow the neuromuscular block to recover spontaneously. Tensilon (edrophonium) challenge test is useful in distinguishing myasthenic crisis from cholinergic crisis. • Aspiration, pneumonia, inadequate cough, atelectasis • Need of ventilatory assistance in the postoperative period due to respiratory failure • Rule out pneumothorax and phrenic nerve damage in case of thymectomy.

REFERENCES

1. irsch NP. Neuromuscular junction in health and disease. Brit J Anaesth. 2007;99(1):132– 138. 2. O’Neill GN. Acquired disorders of the neuromuscular junction. Int Anesthesiol Clin. 2006;42(2):107–121. 3. Tripathi M. The effect of the use of pyridostigmine and requirement of vecuronium in patients with myasthenia gravis. Journal of Postgraduate Medicine. 2003;49:311–315. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary function tests • Functional residual capacity • Anterior mediastinal mass • Flow volume loops

CODES ICD9 • 358.00 Myasthenia gravis without (acute) exacerbation • 358.01 Myasthenia gravis with (acute) exacerbation ICD10 • G70.00 Myasthenia gravis without (acute) exacerbation • G70.01 Myasthenia gravis with (acute) exacerbation

CLINICAL PEARLS

• Assess severity of the disease. • Evaluate the adequacy of drug therapy and optimize the patient’s condition. • Use of regional or local anesthesia, whenever possible • Avoid muscle relaxants and use ultra-short–acting anesthetics. • Avoid postoperative ventilation, whenever possible. • Admission to ICU for postoperative monitoring. • MG may worsen during the course of pregnancy. The first trimester and the month postpartum are the periods of highest risk of exacerbation.

MYASTHENIC SYNDROME Fabrizio Racca, MD Elena C. Capello, MD Federica Manfroi, MD V. Marco Ranieri, MD

BASICS DESCRIPTION

• Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune presynaptic neuromuscular junction (NMJ) disorder. It results from antibodies against voltage-gated calcium channels which are involved with acetylcholine (ACh) release. • The clinical picture is characterized by: – Weak proximal limb muscles – Depressed tendon reflexes – Respiratory failure – Abnormal autonomic function such as dry mouth, gastrointestinal slowing, postural hypotension – Oropharyngeal and ocular muscles are usually spared. – Weakness that improves with sustained contraction • Approximately one-half of LEMS cases are associated with a malignancy, mainly small-cell lung cancer. EPIDEMIOLOGY Incidence

• The true incidence of LEMS is unknown, but the condition is uncommon and occurs much less frequently than myasthenia gravis. • In a population-based study from a region of Holland with 1.7 million inhabitants, 220 cases of myasthenia gravis and 10 of LEMS were identified over a 9-year period. Prevalence

• Cancer is present or later found in ∼40% of patients; clinical manifestations frequently precede cancer identification. • LEMS is most commonly seen with small-cell lung cancer (∼3%). • More common in middle aged patients. • Male:female 2:1 ratio.

Morbidity

• Respiratory failure • Mostly associated with the underlying disease or cancer

Mortality

Mostly associated with the underlying disease or cancer ETIOLOGY/RISK FACTORS

• Cancers: Small-cell lung cancer, as well as non-SCLC, lymphosarcoma, malignant thymoma, cancer of the breast, stomach, colon, or prostate. • Drugs that may worsen the muscular weakness include aminoglycosides, fluoroquinolones, macrolides, beta blockers, diuretics, procainamide, magnesium salts, calcium channel blockers, intravenous iodinated contrast.

PATHOPHYSIOLOGY

• LEMS is an autoimmune disorder that reduces ACh release from the presynaptic nerve terminals. Antibodies directed against the voltage-gated calcium channel interfere with the release of Ach, resulting in muscle weakness. ACh binding and its effect on the postsynaptic membrane are not impaired, neither is the ACh receptor. • In patients with cancer, antigens that mimic voltage-gated calcium channels are believed to induce antibodies. In patients without cancer, antibodies to voltage-gated calcium channels are believed to result from an autoimmune state. • Consequently, muscle weakness improves with use as more Ach becomes available in the NMJ. This phenomenon is referred to as postexercise or postactivation facilitation.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess severity of disease and evaluate pulmonary function. • Patients show extreme sensitivity to both depolarizing and nondepolarizing blocking drugs and these should be avoided if possible. • Other non-anesthetic medications may worsen the muscular weakness by inhibiting neuromuscular transmission (see risk factors). • Postural hypotension may be exacerbated by anesthetic induction agents and mechanical ventilation (MV). • Whenever possible, the use of ultra-short acting anesthetics should be administered to avoid postoperative respiratory depression and hypoventilation.

PREOPERATIVE ASSESSMENT SYMPTOMS

Weakness that improves with activity History

• Clinical course • Hospitalizations • Intubations and ICU admissions

Signs/Physical Exam

• Proximal limb motor weakness • Depressed tendon reflexes

MEDICATIONS

• 3,4-diamimopyridine increases ACh release • Guanidine hydrochloride increases ACh release • Pyridostigmine decreases ACh metabolism and resultantly increases the amount of ACh that is available. • Immune suppressors (steroids, azathioprine, cyclosporine) • Plasmapheresis and intravenous immune globulin

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Pulmonary function tests to help predict the need for postoperative mechanical ventilation; specifically, the negative inspiratory pressure and forced vital capacity (FVC). • Arterial blood gases to assess the pCO2 and pO2. • Chest radiograph if aspiration or pneumonia is suspected.

CONCOMITANT ORGAN DYSFUNCTION • Cancer; see risk factor section • Other autoimmune disorders: – Systemic lupus erythematosus – Rheumatoid arthritis – Pernicious anemia – Thyrotoxicosis

CIRCUMSTANCES TO DELAY/CONDITIONS THAT NEEDED OPTIMIZATION

If the patient is poorly controlled, a course of plasmapheresis may be of benefit in the preoperative period. There should be a 24-hour delay between the last plasmapheresis and surgery in order to restore clotting factors.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Continue medications preoperatively to avoid aggravation of symptoms and muscle weakness. • Steroid-dependent patients may require steroid stress dose (hydrocortisone up to 100 mg IV bolus before induction, then 100 mg q8h × 24h). • In general, sedation is avoided as it may cause respiratory compromise.

Special Concerns for Informed Consent

Inform the patient of the potential requirement for prolonged MV. INTRAOPERATIVE CARE Choice of Anesthesia

• Use of regional or local anesthesia should be warranted whenever possible. • Because local anesthetic agents may block neuromuscular transmission, it is better to use techniques which involve the use of small quantities of these agents; therefore, a subarachnoid block is preferable to the use of epidural or caudal anesthesia.

Monitors

• Standard ASA monitors • Monitoring of neuromuscular transmission (nerve stimulator)

Induction/Airway Management

• The airway should be secured with an appropriate size ET tube using a non-paralyzing technique (i.e., without the use of muscle relaxant and after adequate topical analgesia of the pharynx and larynx). Sevoflurane often provides adequate relaxation for tracheal intubation. • When muscle relaxant use is indicated, it is better to use small doses (1/10th of the usual dose) of non-depolarizing drugs.

Maintenance

• Several general anesthetic techniques have been proposed (balanced anesthetic technique or TIVA), although none have been proven to be superior to the other. • Avoid muscle relaxants and use ultra-short acting anesthetics (propofol, sevoflurane, remifentanil) or volatile agents to achieve the relaxation required for surgery. If using nondepolarizing agents, it is best to use small doses with careful monitoring of neuromuscular transmission. • Avoid drugs that can enhance neuromuscular blockade (beta blockers, diuretics, magnesium, calcium channel blockers).

Extubation/Emergence

• Criteria for extubation include: – Head lift (5 seconds) – Negative inspiratory force of >25 cm of H2O

– Tidal volume > 5 mL/kg – Adequate muscle power evidenced by nerve stimulator • Adequate post-operative pain control, pulmonary toilet, and the avoidance of drugs that interfere with neuromuscular transmission facilitate tracheal extubation.

POSTOPERATIVE CARE BED ACUITY

• Post-operative care should be done in the ICU with monitoring of respiratory function as well as chest physiotherapy. • Avoid drugs that may exacerbate motor weakness (see risk factors).

COMPLICATIONS

• Aspiration, pneumonia, inadequate cough, atelectasis

• In addition to postoperative pulmonary complications, laryngeal and respiratory muscle weakness may warrant ventilatory assistance in the post-operative period.

REFERENCES

1. Hirsch NP. Neuromuscular junction in health and disease. Br J Anaesth. 2007;99(1):132– 138. 2. O’Neill GN. Acquired disorders of the neuromuscular junction. Int Anesthesiol Clin. 2006;42(2):107–121. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary function tests • Functional residual capacity • Myasthenia gravis

CODES ICD9 • 358.1 Myasthenic syndromes in diseases classified elsewhere • 358.30 Lambert-Eaton syndrome, unspecified ICD10 • G70.80 Lambert-Eaton syndrome, unspecified • G73.3 Myasthenic syndromes in other diseases classified elsewhere

CLINICAL PEARLS

• Assess severity of the disease. • Evaluate the adequacy of drug therapy and optimize the condition of the patients. Patients may require plasmapheresis or stress dosing of steroids. • Use of regional or local anesthesia, whenever possible. • Avoid muscle relaxants and use ultra-short acting anesthetics. • Avoid post-operative ventilation, whenever possible. • Admission to ICU for post-operative monitoring.

MYOCARDIAL CONTUSION Kenneth F. Kuchta, MD

BASICS DESCRIPTION

• Myocardial contusion is an injury that usually results from blunt trauma. • It does not have a standardized diagnostic criteria; clinical presentation is variable and can range from minor cardiac bruises to severe insults such as cardiac rupture and death. • Unlike much of cardiac disease managed by anaesthetists, the right ventricle tends to be predominantly affected due to its anterior location. Thus right-sided failure takes a predominant place in the pathophysiology of myocardial contusions. EPIDEMIOLOGY Incidence

• The lack of clear clinical diagnostic criteria makes determining the exact incidence difficult. • A very wide range has been reported across the literature following blunt chest trauma: 9.4– 76%. Morbidity

Associated with a higher incidence of perioperative hypotension, arrhythmias, and death. This risk may persist for one month post trauma, but the magnitude of risk has not been clearly defined. Mortality

• Overall mortality is approximately 15%. • One study found that a myocardial contusion in patients with thoracic trauma was associated with a higher operative mortality (e.g., 54% vs. 4.6%), but this seemed to be related to more severe injuries as most of the deaths were attributed to non-cardiac causes (1).

ETIOLOGY/RISK FACTORS

Blunt trauma can result in myocardial contusions due to a variety of mechanisms:

• Energy transfer to the underlying heart from direct impact to the thorax. • An injury due to deceleration of the heart. • Compression of the heart within the thorax (e.g., between the spine and sternum). • Trauma to the abdomen or lower extremities (without direct thoracic trauma) has been implicated via upward displacement of the viscera. PATHOPHYSIOLOGY

• Histopathology of the affected heart muscle can show hemorrhage, edema, necrosis, and polymorphonuclear infiltrates.

• Animal models suggest that the pathogenesis is distinct from ischemic heart disease. Although there is an initial fall in coronary arterial blood flow, it recovers quickly (over a 20-minute period), and the extent of ventricular dysfunction appears to be proportional to direct myocyte injury and necrosis. • The most common complication is arrhythmia and can occur even after mild trauma (leading to the dilemma as to the need for, and the duration of, cardiac monitoring in many trauma patients). • As the right heart lies anterior, it is most commonly involved. As a result, frank cardiac failure from left ventricular failure is less common. Increased pulmonary artery pressure (from lung contusions, ARDS, etc.) may occur concurrently in this setting and can complicate a right ventricular contusion, resulting in right ventricular failure. • Commotio cordis is a cardiac arrest as a result of a low energy impact, often during sports, resulting in a cardiac arrest. – Distinct from a myocardial contusion, as there are no histological findings of trauma to the heart. – Also called a myocardial concussion. – If the impact occurs shortly before the peak of the T wave, the result can be ventricular fibrillation. – Impact during the QRS complex can result in complete heart block.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Anesthetic management should take into account the manifestations of myocardial contusions (which may have presented preoperatively or declare themselves during the case). – Arrhythmias may need to be treated pharmacologically or via cardioversion/ defibrillation. – Recognition that cardiac failure is likely to be right sided: Adequate preload is essential, and thus TEE may be more useful than PA catheter measurements, especially in the setting of concomitant pulmonary contusions, mechanical ventilation, and elevated pulmonary artery pressures.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Often masked by other injuries or intubation in the severely injured. • Chest pain and shortness of breath (though this may be secondary to chest wall trauma or CPR). • Palpitations. • Evidence indicating high impact injuries: – Rib fractures (especially upper) and clavicle fractures – Pulmonary contusions – Pneumothorax and/or hemothorax – Flail chest – Great vessel injuries

History

Any trauma history consistent with the possibility of myocardial injury should prompt further investigation. Myocardial contusion should be considered in high-speed motor vehicle accidents with blunt force trauma (especially chest trauma), auto versus pedestrian trauma, falls, and other deceleration injuries as well as after cardiopulmonary resuscitation. Signs/Physical Exam

• Irregular pulse indicating arrhythmias. • Distended neck veins may indicate right ventricular failure or tamponade. • Muffled heart tones, pulsus paradoxus may further indicate tamponade. • Cardiovascular deterioration (decreased blood pressure, poor peripheral perfusion). • Respiratory failure could represent further deterioration.

TREATMENT HISTORY

• Intubation and mechanical ventilation • Increased oxygen requirement • Temporary pacing for complete heart block

MEDICATIONS

• Antiarrhythmics • Pharmacologic support of cardiac failure

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• EKG, though as the right ventricle is the most commonly affected, this test may have very limited utility (low negative predictive value). – ST and T wave changes are frequent, Q waves are rare. – Sinus tachycardia is the most common arrhythmia, as would be expected in trauma (i.e., low specificity). – Arrhythmias, right bundle branch block (RBBB), and interventricular conduction defects should be sought. – Ventricular tachycardia is very concerning, but may not be captured on a 12-lead EKG (continuous cardiac monitoring is suggested). • Creatinine kinase MB is generally not considered helpful due to frequent concurrent skeletal muscle injuries. • Troponin levels: Troponin I is more specific than troponin T. However, – Injury, especially small areas that may predispose to arrhythmia, may occur without release of troponin. – Hemorrhage or shock without myocardial contusion can result in troponin release. • Echocardiography. – Transthoracic method may be limited by mechanical ventilation, pneumothorax, and difficulty in positioning the patient. – Transesophageal might have some difficulty in imaging the right ventricle (the chamber most often involved) but is still useful for the diagnosis of myocardial contusions and its

complications as well as to assist with cardiovascular management of the patient. • Cardiac catheterization is indicated in the very few cases where coronary lesions are suspected.

CONCOMITANT ORGAN DYSFUNCTION

• Other blunt force injuries: Rib and clavicle fractures, flail chest. • Pulmonary injuries such as pulmonary contusions, ARDS, aspiration, and pneumothorax and/or hemothorax can potentially complicate the diagnosis and management of myocardial contusions, particularly if pulmonary hypertension occurs. • Associated cardiac injuries include: – Myocardial infarction as either a complication, or the cause, of the trauma is a definite and increasing possibility, given the changing population demographics. This can further complicate the diagnosis and management of myocardial contusion. – Coronary artery injury. – Myocardial rupture: The right ventricle is most commonly involved. – Ventricular and atrial septal defects. – Valvular lesions: Most often affects the aortic and mitral valves due to the higher intracavitary pressures. – Pericardial effusion or hemopericardium. – Pericardial rupture with the potential for myocardial herniation. – Aortic rupture.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Ideally the diagnosis of myocardial contusion should be established, including the extent of the lesion and the related complications prior to surgery. The nature of much of trauma injuries and surgery, however, does not frequently allow this luxury. Diagnostic effort may need to occur in the operating room (e.g., via TEE), although this may prove difficult due to the demands of merely caring for an unstable trauma patient. • Further workup, however, may be possible in the more elective subsequent procedures that are often part of the care of the trauma patient.

CLASSIFICATIONS Not established

TREATMENT PREOPERATIVE PREPARATION Premedications

In the setting of confirmed or suspected myocardial contusion, caution with any premedication may be warranted to avoid compromising the patient’s hemodynamic status. Special Concerns for Informed Consent

If applicable, informing the patient and/or their family of the increased risk due to a possible or confirmed myocardial contusion may be warranted. This might include possible additional

monitors that might be needed during the surgery. INTRAOPERATIVE CARE Choice of Anesthesia

• Usually dictated by concomitant injuries and necessary surgery. • In rare circumstances, sedation may be utilized to avoid general anesthesia and positive pressure ventilation, if right ventricular function is compromised.

Monitors

Depending upon the extent of the contusion and its complications, additional monitoring might be considered, including arterial, central, and pulmonary pressure monitoring as well as cardiac output monitoring and TEE. Induction/Airway Management

Careful consideration with regard to hemodynamic changes may dictate a “slow careful induction”; however, a full stomach and potentially unstable cervical spine may complicate this consideration. Maintenance

• While no specific anesthetic is indicated, the goal should be to optimize hemodynamics in a setting of potentially impaired cardiac function. • Increased FIO2 is often administered. • Consider the use of an ICU ventilator to allow for additional modes of ventilation (high frequency, etc).

Extubation/Emergence

As per the extent of injury and the course of the surgery.

POSTOPERATIVE CARE BED ACUITY

• Dependent upon the acuity of the patient’s overall condition and extent of the injury. • Strongly consider a monitored setting if there is a suspicion of a myocardial contusion in an otherwise stable (lower acuity) patient due to the potential for developing arrhythmias.

MEDICATIONS/LAB STUDIES/CONSULTS

• Continued surveillance for, and support of, the manifestation of myocardial contusion as outlined above may be indicated. • Cardiology consult, if not already obtained, should be considered.

COMPLICATIONS

• Pericardial effusions and hemopericardium can occasionally lead to late constrictive pericarditis (at times with significant calcifications) and may require pericardiectomy. • Ventricular aneurysms are also occasionally seen as a late complication with variable significance.

REFERENCES

1. Devitt JH, McLean RF, McLean BA. Perioperative cardiovascular complications associated with blunt thoracic trauma. Can J Anesth. 1993;40:197–200. 2. Baxter BT, Moore EE, Synhorst DP, Reiter MJ, Harken AH. Graded experimental myocardial contusions: impact on cardiac rhythm coronary artery flow, ventricular function, and myocardial oxygen consumption. J Trauma. 1988;28(10):1411–1417.

ADDITIONAL READING

• Orliaguet G, Ferjani M, Riou B. The Heart in Blunt Trauma. Anesthesiology. 2001;95:544– 548. • Schultz JM, Trunkey DD. Blunt cardiac injury. Critical Care Clinics. 2004;20:57–70.

See Also (Topic, Algorithm, Electronic Media Element) • Pneumothorax • Trauma • Ventricular septal defect

CODES ICD9 • 861.01 Contusion of heart without mention of open wound into thorax • 861.11 Contusion of heart with open wound into thorax ICD10 • S26.91XA Contusion of heart, unsp w or w/o hemopericardium, init • S26.91XD Contusion of heart, unsp w or w/o hemopericardium, subs • S26.91XS Contusion of heart, unsp w or w/o hemopericardium, sequela

CLINICAL PEARLS

• While most of our thinking about the heart (diagnosis and treatment) relates to the left ventricle, much of the pathophysiology of myocardial contusions relates to the right side. This is due to the orientation of the heart in the chest; the heart lies rotated, thus the right ventricle is closest to the sternum and is most vulnerable to blunt trauma. • In at least two scenarios, trauma patients may present with more traditional appearing cardiac events (with coronary-based pathophysiology) that would dictate angiography with possible stenting or bypass. – A young trauma patient with classic findings of a myocardial infarction (on EKG, enzymes and possibly echo) should be considered for the possibility of having a coronary injury. – Older patients may have suffered atherosclerotic-related myocardial infarction as either the cause of the trauma or as a result of the injury. With the aging trauma population, this added consideration only indicates how much more complex the differential diagnosis will become in the future.

MYOCARDIAL OXYGEN DEMAND Emily Gordon, MD

BASICS DESCRIPTION

• The balance between myocardial oxygen supply and demand is critical to the proper function of the heart. If myocardial oxygen demands are not met, myocardial ischemia, infarction, arrhythmias, or death may result. • Oxygen demand is not equivalent to oxygen consumption. Demand is related to need. Consumption is the actual amount of oxygen used per unit time. • The myocardium uses oxygen primarily for effective contraction. Requirements for basal metabolism comprise only 10–20% of total O2 consumption. Requirements of the electrical conduction system are even less. • The major determinants of myocardial oxygen demand are: – Heart rate – Contractility – Myocardial (systolic) wall tension

PHYSIOLOGY PRINCIPLES

• Myocardial oxygen consumption (VO2): Large amounts of ATP are needed for the proper

function of the myocardium. Aerobic metabolism (most efficient source) of fatty acids is the primary mechanism by which ATP is regenerated at rest. • Oxygen extraction: The myocardium is a tightly regulated tissue which excels in its ability to extract oxygen from the blood that enters the coronary arteries. In the non-stressed state, the myocardium extracts 70–75% of the oxygen from the red blood cells/hemoglobin that flow through the coronary arteries. Venous saturation thus equals ∼25–30%. • Coronary blood supply is comprised of coronary blood flow and blood oxygen carrying capacity. Furthermore, because coronary oxygen extraction is near maximal under resting conditions, the primary mechanism to meet increased oxygen demand is through enhanced delivery; thus, it is a dynamic process that is modulated by multiple parameters. – Autoregulation is the intrinsic mechanism to maintain a constant blood flow over a range of perfusion pressures (60–160 mm Hg); changes in pressure are met by reciprocal changes in resistance. Local metabolic and myogenic factors appear to play a role. Myogenic factors describe the response of smooth muscles to the shear forces of perfusion pressure. Metabolic factors (e.g., oxygen and carbon dioxide tension and adenosine) affect vascular smooth muscle tone as their concentrations vary. In other words, an increase in the PaCO2 would stimulate vasodilation and “washout.”

– Humoral factors include circulating agents such as angiotensin II, serotonin, thromboxane, prostacyclin, and bradykinin that effect coronary resistance. – Neural control describes autonomic innervation such as alpha, beta, and parasympathetic

activity. – Diastolic time: The left ventricle’s systolic pressures exceed the coronary artery’s diastolic perfusion pressure; thus extravascular compressive forces prevent perfusion during systole. – Blood oxygen–carrying capacity is the sum of oxygen bound to hemoglobin and dissolved in blood. It is primarily determined by the hemoglobin level (capable of binding 1.39 mL of oxygen per gram); dissolved oxygen is poorly soluble in blood (0.003), thus, its contribution is minimal. This serves as the physiologic basis for blood transfusions. • Oxygen demand: Heart rate has the greatest effect on myocardial work and oxygen demand. – Heart rate: For every heartbeat, the myocardium undergoes electrical depolarization and repolarization, generates contractility, ejects blood against the wall tension (preload or volume work and afterload or pressure work), and undergoes relaxation. Note: Tachycardia will decrease the diastolic perfusion time which primarily affects the left ventricle’s blood supply. – Cardiac contractility or inotropy is the intrinsic ability of the cardiomyocyte to shorten from its individual resting fiber length; it is independent of preload and afterload. Contraction results from myosin and actin filament binding and is dependent upon intracellular calcium ion concentration. Increases in sympathetic tone or catecholamine state, calcium levels, heart rate, as well as inotropic drugs (beta agonists, calcium, glucagon, phosphodiesterase inhibitors) have a positive effect on contractility. – Myocardial wall tension: The law of LaPlace states that wall tension is directly proportional to the chamber radius and pressure; it is inversely proportional to the wall thickness. Radius is primarily determined by preload (changes in blood volume or chamber size). Pressure is primarily determined by the afterload which is a function of systemic vascular resistance, the aortic valve, and blood viscosity. Myocardial wall thickness is responsible for long-axis function secondary to endocardial and midwall fractional shortening. However, wall thickness is not responsible for shortaxis function. Tension is dynamic (aside from wall thickness) and can vary with each heartbeat and throughout the contraction (chamber size decreases with ejection).

ANATOMY

• Coronary arteries: The presence of a stenotic lesion results in a pressure drop that is proportional to the fourth power of the radius, the length of the plaque, and the magnitude of flow. • The subendocardium (inner one-third to one-fourth of the myocardium) is most susceptible to the effects of CAD or to a reduction in perfusion pressure. This is secondary to: – Adjacent intraventricular pressures (left ventricular end-diastolic pressure) – Limited maximal vasodilator response – Blood flow only occurs during diastole; during systole, extravascular compressive forces (mechanical forces that compress coronary vasculature) are greatest

PHYSIOLOGY/PATHOPHYSIOLOGY • Heart rate is increased by: – Pain or inadequate anesthesia

– Postoperative shivering – Catecholamines – Hypovolemia – Anemia – Hypoxia – Fever – Hyperthyroidism – Administration of vagolytic drugs (e.g., atropine, glycopyrrolate) • Cardiac contractility is increased by: – Catecholamines – Increased heart rate: The Treppe or Bowditch effect describes an autoregulatory method by which myocardial contractility increases with an increase in heart rate. This mechanism is believed to result from an inability of the sodium–potassium ATPase (moves sodium extracellularly) to keep up with the sodium–calcium exchanger (moves sodium intracellularly) during tachycardia. This results in increased intracellular levels of calcium. • Myocardial wall tension is increased by: – Increased ventricular diameter (volume overload, impaired ejection fraction, dilated cardiomyopathy). – Increased aortic pressure: Hypertension, aortic stenosis, and hemoconcentration increase the pressure that needs to be generated in order to eject blood from the left ventricle.

PERIOPERATIVE RELEVANCE

• Induction of anesthesia – Laryngoscopy and airway instrumentation can result in excessive catecholamine release. The goal is to pre-empt with opioid or anti-hypertensive administration, decrease laryngoscopy time, ensure an adequate depth of anesthesia (and time for onset), and be prepared to treat hemodynamic perturbances (esmolol, nitroglycerin, additional anesthetic agents such as propofol or volatile agents). • Maintenance of anesthesia – Pain and awareness under anesthesia can result in tachycardia; ensure an adequate depth of analgesia and anesthesia. This may become challenging in the hypotensive patient. Consider the use of nitrous oxide and decrease of volatile agent, volume administration, or phenylephrine infusion to maintain adequate mean arterial pressures. – Perioperative beta-blockade may be titrated to a heart rate of 50–80 beats/min or bolused during catecholaminergic states. – Changes to desflurane concentrations can result in sympathetic discharge and tachycardia. – Normothermia may be maintained with blankets or warming devices (convective blankets, warming fluids, etc.) – Optimize volume status: Hypovolemia can result in a reflex tachycardia, whereas hypervolemia increases the myocardial chamber radius (preload). • Postoperative/PACU care – Provide adequate pain control: A multimodal approach may include anti-inflammatory medications, regional nerve blocks, and opioids, as appropriate. – Optimize volume status: The postoperative period may be marked by fluid flux between the intracellular and extracellular compartments as well as continued bleeding.

– Treat postoperative shivering (warming techniques, meperidine, clonidine). – Ensure adequate oxygenation: Residual sedatives or narcotics can decrease the functional residual capacity and result in hypoxia (increased sympathetic state). Consider nasal cannula, facemask, deep breathing, coughing or CPAP/BIPAP when indicated.

EQUATIONS

• MVO2 = CBF × (CaO2 – CvO2); where MVO2 is mixed venous oxygen saturation, CBF is cerebral blood flow, CaO2 is the arterial blood oxygen content, and CvO2 is the venous

blood oxygen content • A-VO2 = (CaO2 – CvO2) is the arterial-venous oxygen content difference (mL O2/mL blood) • CO = O2 consumption/A-VO2 difference

• Law of LaPlace: T = ΔPr/2h, where T is tension, ΔP is change in pressure, r is radius, and h is myocardial wall thickness

REFERENCES

1. DeFily DV, Chilian WM. Coronary microcirculation: autoregulation and metabolic control. Basic Res Cardiol. 1995;90(2):112–118. 2. Duncker DJ, Bache RJ. Regulation of coronary blood flow during exercise. Physiol Rev. 2008;88(3):1009–1086. 3. Duncker DJ, Merkus D. Regulation of coronary blood flow. Effect of coronary stenosis. Arch Mal Coeur Vaiss. 2004;97(12):1244–1250. 4. Ardehali A, Ports TA. Myocardial oxygen supply and demand. Chest. 1990;98(3):699–705. See Also (Topic, Algorithm, Electronic Media Element) • Coronary arteries • Intraoperative myocardial ischemia • Chronic angina • Hypothermia • Myocardial oxygen supply • Preload • Afterload

CLINICAL PEARLS

• The myocardial oxygen demand cannot be easily measured in the perioperative period. To that extent, a clear understanding of the various factors that affect demand, as well as supply, are critical to optimize an adequate balance and avoid ischemia.

NARCOTIC WITHDRAWAL Angela T. Hsu, MD

BASICS DESCRIPTION

• Sudden opioid abstinence or administration of an opioid antagonist in a narcotic-dependent individual may induce a traumatic reaction in the body, collectively characterized as opioid withdrawal syndrome. • Opioid withdrawal is rarely life-threatening, but is highly unpleasant and may complicate care in the perioperative period. EPIDEMIOLOGY Incidence

• Narcotic pain medications are the most frequent class of medications that are misused or abused; they accounted for 397,160 ED visits in 2009. • In a 2009 US survey of ER departments, heroin accounted for 213,118 visits.

Prevalence

• In 2002, the prevalence of heroin dependence was estimated at 0.14% of the US population. • Although ED visits from heroin usage has not changed significantly from 2004 to 2009, narcotic painkiller related visits have risen dramatically. • According to recent estimates, >2 million people in the US are abusing prescription opioids.

Morbidity

• Narcotic withdrawal is uncomfortable and associated with sympathetic nervous system hyperactivity. • Patients with underlying cardiac risk factors may be predisposed to arrhythmias, ischemia, and subsequent cardiovascular collapse during withdrawal. Mortality

Fatality is rare.

ETIOLOGY/RISK FACTORS

In chronic opioid-dependent patients, withdrawal may be precipitated by:

• Abrupt cessation or a significant decrease in the regular dosing of opioids • Administration of an opioid antagonist: Nalmefene, naltrexone, naloxone • Administration of an opioid agonist–antagonist: Pentazocine, butorphanol, nalbuphine, buprenorphine PHYSIOLOGY/PATHOPHYSIOLOGY

• Opioid receptors were once thought to be found exclusively in the CNS, but recent studies

show that they are found in virtually all organ systems. • Endogenous opioids not only modulate the perception of pain, but also help regulate many other physiologic functions, including: – Respiration – Blood pressure – Shock and stress states – Vasopressin release and free water clearance by the kidneys • Neuroadaptation results from the regular use of opioids. – There is a downregulation of opioid receptors with the continuous presence of high levels of opioid agonists. – At the cellular level, there are changes in several components of cyclic adenosine monophosphate (cAMP) signal transduction cascades. – Physical dependence usually occurs 1–4 weeks after continuous opioid usage. • Withdrawal from opioids can result in a sudden increase in cAMP levels in many organ systems. The sympathetic nervous system is one of the most prominent systems affected by opioid withdrawal. – Epinephrine levels increase ∼30 times and norepinephrine levels increase ∼3 times, leading to restlessness, rhinorrhea, lacrimation, diaphoresis, myosis, piloerection, and CV changes. – Explains the benefit of clonidine in attenuating withdrawal symptoms

PREVENTATIVE MEASURES

Management of heroin abusers and chronic opioid-dependent patients • Maintain opioids during the perioperative period to avoid withdrawal. Long-acting opioids such as methadone or buprenorphine formulations may be used in combination with shortacting opioids to decrease troughs in opioid levels and treat breakthroughs, respectively. • Avoid opioid antagonists and opioid agonist–antagonists in these patients since they can precipitate acute withdrawal.

DIAGNOSIS • History: As narcotic withdrawal is not associated with altered mental status (AMS), patients can often tell you if they are undergoing withdrawal secondary to opioids. They can also tell you their usual opioid dosing schedule and the timing of their last dose. • Signs and symptoms – Manifest between 5 and 24 hours from the last dosing. Methadone withdrawal may take longer to present, but is usually between 24 and 48 hours. – Peak withdrawal is 36–72 hours after the last dose. For methadone, it is 72–96 hours after the last dose. – Duration is usually 5–10 days. Methadone withdrawal typically lasts 2–3 weeks, sometimes longer. – Signs: Pupillary dilation, sweating, piloerection, tachycardia, ventricular dysrhythmias, vomiting, diarrhea, hypertension, yawning, fever, rhinorrhea – Psychological withdrawal symptoms, such as dysphoria and insomnia, may last weeks to

months. – Symptoms: Craving for opioids, restlessness, irritability, increased sensitivity to pain, nausea, abdominal cramps, myalgia, dysphoria, insomnia, anxiety • Labs: Urine or blood toxin screen confirms opioids and/or other illicit substances.

DIFFERENTIAL DIAGNOSIS

• Other substances that cause autonomic instability. AMS, disorientation, hallucinations, and seizures are not found in narcotic withdrawal but may be found when withdrawing from: – Alcohol – Benzodiazepines – Barbiturates • Other sedatives/hypnotics

TREATMENT For patients undergoing anesthesia for emergency procedures: • Abort withdrawal symptoms by administering opioid agonists. • Check electrolytes, BUN, and creatinine if there has been significant dehydration, vomiting, or diarrhea. Give fluids or replete electrolytes, as indicated. • Consider regional anesthesia when possible. • For general anesthesia, a balanced technique with volatile anesthetics +/– nitrous is recommended. • Beware of perioperative hypotension as intravascular volume depletion is common, given the fevers, malnutrition, chronic infection, and adrenocortical deficiency often associated with opioid addiction and withdrawal. • Clonidine, a central acting alpha-2 agonist, may be given orally or applied via a transdermal patch to help with sympathetic nervous system hyperactivity found in narcotic withdrawal. • NSAIDs, such as ibuprofen, are given to attenuate muscle aches. • Benzodiazepines are sometimes used for anxiety, insomnia, and muscle cramps. However, given the potential for abuse and high risk of physical dependence, this is not considered first-line therapy. • For patients undergoing procedures or for acute pain consultation where narcotic detoxification is desired: – Consider administering the original opioid dosing and planning a gradual taper. – Alternatively switch to long-acting methadone or buprenorphine for gradual detoxification. Note: Patient must be in full withdrawal prior to starting buprenorphine. As an agonist/antagonist, buprenorphine can precipitate more severe withdrawals if given prematurely. • Ultra-rapid opiate detoxification in which patients are given large doses of opioid antagonist and placed under general anesthesia for the most severe stages of withdrawal, has become popular. However, compared to buprenorphine- or clonidine-assisted opioid detoxification, it is not as effective or safe. Several serious adverse events, including possibly fatal cardiac and pulmonary complications, have been linked to ultra-rapid opioid detoxification. • Instead of detoxification, consider lifelong maintenance on methadone or buprenorphine

since these have been associated with much higher rates of long-term program retention. Studies on methadone maintenance programs have shown decreased medical comorbidity, transmission of HIV, mortality, and increased social functioning.

FOLLOW-UP The relapse rate for opioid addiction is high. Significant psychosocial support is needed beyond the withdrawal period to prevent relapse.

REFERENCES

1. Administration SAaMHS. Results from the 2007 National Survey of Drug Use and Health: National Findings. Rockville, MD: Administration SAaMHS, 2008. 2. Collet BJ. Opioid tolerance: The clinical perspective. Br J Anaesth. 1998;81:58–68. 3. Collins ED, Kleber HD, Whittington RA, et al. Anesthesia-assisted vs. buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction: A randomized trial. JAMA. 2005;294:903–913. 4. Kaye AD, Gevirtz C, Bosscher HA, et al. Ultra-rapid opiate detoxification: A review. Can J Anaesth. 2003;50(7):663–671. 5. Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348:1786–1795. 6. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. The DAWN Report: Highlights of the 2009 Drug Abuse Warning Network (DAWN)—Findings on Drug-Related Emergency Department Visits. Rockville, MD, December 28, 2010. See Also (Topic, Algorithm, Electronic Media Element) • Drug abuse in pregnancy • Alcohol withdrawal syndrome

CODES ICD9 292.0 Drug withdrawal ICD10 F11.23 Opioid dependence with withdrawal

CLINICAL PEARLS

• Opioid withdrawal is rarely life-threatening, but may complicate care in the perioperative period. • Clonidine may attenuate the sympathetic nervous system hyperactivity found in withdrawal.

• Consider the possibility of abuse of other illicit substances in patients who abuse opioids. • Consider comorbid psychiatric conditions in narcotic withdrawal patients. • When caring for opioid addicts, particularly the intravenous abuser, beware that these patients often have associated infectious problems: hepatitis, HIV, endocarditis, septic thrombophlebitis, cellulitis, abscesses, aspiration pneumonitis, malnutrition.

NEGATIVE PRESSURE PULMONARY EDEMA Agnes Miller, MD Kalpana Tyagaraj, MD

BASICS DESCRIPTION

• Negative pressure pulmonary edema (NPPE) is an uncommon, but well-recognized clinical entity that results from the negative intrathoracic pressure generated during spontaneous ventilation with concurrent upper airway obstruction. • The pulmonary edema results from either: – “Pulling” of fluids from the pulmonary capillary bed into the alveoli (Starling forces), or – Injury to the pulmonary microvascular membranes from severe mechanical stress that results in capillary “leaking” of fluid. • NPPE can result from laryngospasm or biting, commonly at induction or extubation, as well as from epiglottitis, tumors, obesity, hiccups, or obstructive sleep apnea. • Clinical manifestations result from ventilation and perfusion difficulties (V/Q mismatching or shunt) with a frequent need for reintubation and temporary ventilatory support. EPIDEMIOLOGY Prevalence

• All anesthetic practices: 0.05–0.1%. • Laryngospasm post-extubation or biting of the endotracheal tube (ETT): 74% • Initial airway management secondary to laryngospasm or obstruction from large head and neck tumors: 26%. Prevalence

Development of pulmonary edema following active intervention for acute upper airway obstruction: 11% Morbidity/Mortality

• In undiagnosed cases it can range between 11% and 44%. • If diagnosed and treated promptly, it is less than 1%.

ETIOLOGY/RISK FACTORS • Etiology – Laryngospasm – ETT biting – Airway trauma – Upper airway collapse – Bronchial obstruction – Foreign body aspiration

– Postoperative residual curarization (impairs the upper airway dilator muscle strength while preserving inspiratory muscle function) • Patient characteristics – Young, healthy, athletic (capable of generating large negative intrathoracic pressures during an obstructive event) – Obstructive sleep apnea • Surgical procedures – Oropharyngeal surgery, particularly for tumors or other potentially obstructing masses

PHYSIOLOGY/PATHOPHYSIOLOGY

• The pathogenesis of NPPE is related to the development of high negative intrapleural pressure by vigorous inspiratory efforts against an obstructed upper airway. • 2 different mechanisms may explain the development of pulmonary edema during airway obstruction: – Starling forces: High negative intrathoracic pressures draw fluid out of micro-vessels into the peri-microvascular interstitium. Cardiogenic pulmonary edema states (CHF, fluid overload) have a similar presentation but result from positive capillary pressures that “push" fluid out of micro-vessels. During upper airway obstruction and forceful inspiration, pressure in the trachea and lower airways will decrease markedly (become more negative). The pressure in the pleural space decreases (becomes more negative) by exactly the same amount. The pressure in the pulmonary vessels decreases by much less, thus increasing the pressure difference between the inside and the outside of the capillaries and accelerating the formation of interstitial fluid. – Disruption of the alveolar epithelium and pulmonary microvascular membranes from severe mechanical stress occurs, leading to increased pulmonary capillary permeability and protein-rich pulmonary edema (this resembles non-cardiogenic pulmonary edema states such as acute respiratory distress syndrome). – Starling equation: Q = K [(Pmv − Ppmv) − (πmv − πpmv)], where Q = Net transcapillary flow of fluid K = Transcapillary permeability Pmv = Hydrostatic pressure in microvessels Ppmv = Perimicrovascular interstitium

πmv = Plasma protein osmotic pressure in the peripheral vessels

πpmv = Protein osmotic pressure in the perimicrovascular interstitium

• Respiratory dynamics: – Pulmonary edema is the pathologic accumulation of fluid in the lung interstitium, and later alveoli, producing impairment in gas exchange. – Pulmonary edema leads to V/Q mismatching since less alveoli are participating in gas exchange. The severity of V/Q mismatch correlates with the severity of the pulmonary edema. – Lung edema leads to decreased lung compliance, which leads to an increased work of breathing.

PREVENTATIVE MEASURES

• Bite block to prevent biting on the ETT • In patients prone to upper airway obstruction, consider prophylactic placement of an oral airway or nasal trumpet. • Treat laryngospasm aggressively with positive pressure ventilation or succinylcholine.

PREOPERATIVE ASSESSMENT • History: Acute upper airway obstruction in spontaneously ventilating patients • Signs and symptoms: Onset can occur within minutes after the relief of obstruction. Can present as stridor, wheezing, decreased SaO2%, or frothy or pink sputum. • Studies: EKG is typically normal, but may demonstrate right heart strain. • Laboratory findings: None that are specific • Radiographic findings: Peripheral or central asymmetric peribronchial infiltrates

DIFFERENTIAL DIAGNOSIS

• Cardiogenic pulmonary edema • Neurogenic pulmonary edema • Fluid overload • Acute respiratory distress syndrome • Non-cardiogenic pulmonary edema (e.g., acute respiratory distress syndrome).

TREATMENT • The goal is to maintain a patent upper airway and administer supplemental oxygen. • Consider a trial of CPAP or pressure support as an alternative to intubation. The aim of noninvasive respiratory support is to: – Partially compensate for the increased work of breathing – Improve alveolar recruitment with better gas exchange – Reduce left ventricular afterload – Increase cardiac output and improve hemodynamics • In severe cases, consider re-intubation. Ventilation mode should be similar to the mode used during acute lung injury (i.e., small tidal volumes [6 mL/kg], increased respiratory rate [14–18 breaths/minute], and attempt to keep peak pressures <30 cm H2O).

• Pharmacologic management: – Bronchodilators may be used to treat bronchospasm and possibly increase the rate of alveolar fluid clearance. – Diuretic use is controversial and may not be necessary. • Extubation criteria: – Ensure resolution of pulmonary edema. – General extubation criteria are met.

FOLLOW-UP

• Generally, a benign condition that resolves in 24–48 hours when recognized early and necessary supportive measures are instituted. • If NPPE develops at iInduction: – An elective case should be postponed. – An emergent case should proceed after the airway has been secured. Implement smaller tidal volumes, increased respiratory rate, and maintain low peak pressures.

REFERENCES 1.

rodel DJ. Casescenario: Acute postoperative edema.Anesthesiology.2010;113:200–207.

negative

pressure

pulmonary

2. oldenberg JD. Negative pressure pulmonary edema in the otolaryngology patient. Otolaryngol Head Neck Surg. 1997;117:62–66. 3. Fremont RD. Post-obstructive pulmonary edema: A case for hydrostatic mechanisms. Chest. 2007;131:1742–1746. 4. Lorch DG. Post-extubation pulmonary edema following anesthesia induced by upper airway obstruction. Are certain patients at increased risk? Chest. 1986;90:802–805. 5. Majewski J, Górnik-Właszczuk E, Koczy B, et al. Negative pressure pulmonary edema and hemorrhage. Anestezjol Intens Ter. 2010;42(2):90–93. [in Polish].

ADDITIONAL READING • www.theasahq.org • www.uptodate.com

See Also (Topic, Algorithm, Electronic Media Element) • Cardiogenic pulmonary edema • Non-cardiogenic pulmonary edema • Laryngospasm • Postoperative pulmonary complications

CODES ICD9 518.4 Acute edema of lung, unspecified ICD10 J81.0 Acute pulmonary edema

CLINICAL PEARLS

• Pulmonary edema can result from cardiogenic or neurogenic causes, fluid overload, or acute respiratory distress syndromes, as well as from the generation of negative pressure against upper airway obstruction. It is possible that many of the cases of postoperative oxygen

desaturation are due to unrecognized NPPE. • This form of pulmonary edema is typically transient, self-limited, and easily resolved by the maintenance of a patent upper airway and supplemental oxygen. Mechanical ventilation may be needed for a very brief period of time. • The oxygen desaturation following NPPE can be confused with pulmonary aspiration and pulmonary embolism, which are potentially associated with serious morbidity and mortality.

NEPHRECTOMY Emily L. Drennan, MD

BASICS DESCRIPTION General

• A nephrectomy is the surgical removal of all, or part, of the kidney. • Nephrectomy procedures include: – Simple: Removal of the kidney alone. Indications include infection, obstruction, and hypertension. – Partial: Removal of a portion of the kidney. Indications include mass or tumor. Has increased in popularity as a means to preserve nephrons in patients with renal masses that are <4 cm in size and located in an accessible region of the kidney. – Radical: Removal of the kidney, surrounding fat, adrenal gland, and ureter. Indications include renal cell carcinoma. – Donor: Removal of a healthy kidney, ureter, and as much of the renal vessels as possible. Indication is for living related renal transplant. • Procedures: Nephrectomies can be done open, laparoscopically, or with robotic equipment. The benefits of the laparoscopic approach include less pain, earlier PO intake, and shorter hospitalization. These must be weighed against the potential for longer operative times, and are dependent on the surgeon’s level of experience. Additionally, the pneumoperitoneum significantly decreases renal blood flow. – Open and laparoscopic nephrectomy involves exposure of the kidney, control and ligation of the renal vessels at the renal hilum, ligation of the ureter, and removal of the kidney. – Open and laparoscopic partial nephrectomy involve exposure of the kidney and renal hilum, delineation of the mass (via direct visualization or ultrasound), submersion of the kidney in ice (to decrease renal metabolic rate/oxygen consumption), renal artery clamping, resection of the mass in as brief a period of time as possible (to decrease ischemia time), and reperfusion. Following reperfusion, bleeding is controlled, the renal parenchyma is closed to avoid urine leakage, and the wound is closed. In patients at highrisk for post-resection renal failure, manual compression of the renal artery may be performed instead of clamping. Position

• Flexed lateral decubitus: Retroperitoneal approach • Supine: Transabdominal approach

Incision

• Laparoscopic: 3–4 small incisions in the upper abdomen, one at the umbilicus • Open nephrectomy: Subcostal, lumbar, retroperitoneal, or flank incision

Approximate Time

• 2–3 hours for either approach • Laparoscopic times are highly dependent on surgeon experience.

EBL Expected

• 200–500 mL • Blood loss is significantly higher for partial nephrectomies and nephrectomies performed to remove large tumors involving renal vessels or the inferior vena cava (IVC).

Hospital Stay

• Laparoscopic: 1–2 days • Open: 5–7 days

Special Equipment for Surgery

• Laparoscopic: Laparoscopy monitors and equipment • Partial nephrectomy may require intraoperative ultrasound to localize lesions. • Nephrectomy for renal cell cancer may require cardiopulmonary bypass if there is significant tumor extension into the IVC.

Pediatric Considerations

• Indications include renal mass, non-functioning kidney, duplex anomalies of the kidney, vesicoureteric reflux, and multicystic dysplastic kidney. • Laparoscopic, open, partial, and total nephrectomies are all possible depending on the pathology.

EPIDEMIOLOGY Incidence

In the US, approximately 25,000 nephrectomies and 5,000 partial nephrectomies are performed annually. Prevalence

• Renal cell carcinoma is most prevalent in males aged 50 years and older.

Morbidity

• Renal failure requiring dialysis • Cardiovascular events, including perioperative myocardial ischemia • Hemorrhage • Respiratory complications, including pneumonia, pulmonary embolus, or respiratory failure • Injury to surrounding structures, particularly the spleen or pancreas with left nephrectomies • Urinary leak, if partial nephrectomy undertaken

Mortality

• Dependent on the indication for the procedure and ranges from <1% to 5% • Simple donor nephrectomies have a perioperative mortality of 0.03% • Nephrectomies for renal cell cancer have a mortality rate dependent on the stage of their

cancer and medical comorbidities.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• If partial nephrectomy is performed, preparation for blood loss during the resection of the mass is crucial. • Avoid further insult to remaining kidney – Nephrotoxic drugs – Hypotension – Hypovolemia – Sepsis

PREOPERATIVE ASSESSMENT SYMPTOMS

• May include a sensation of fullness at the site, pain, hematuria, and hypertension • Donor nephrectomies are typically healthy.

History

• Indication for the procedure • Obtain a surgical history to assess potential difficulty with the surgical procedure related to adhesions. • Obtain a social history, including tobacco abuse, to assess risk of intraoperative and postoperative complications.

Signs/Physical Exam

No specific physical exam findings; a palpable flank mass may be present in patients with renal tumors. MEDICATIONS

• Erythropoietin for patients with renal insufficiency and anemia • Oral antihypertensive agents to control blood pressure

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Type and Screen • CBC • BMP • UA • Creatinine clearance • EKG, if age >50 years or clinical risk factors present • Most patients will have a preoperative CT scan that delineates the size and extent of the mass as well as identifies abnormal anatomy that may prolong surgery or increase blood loss. • In patients with renal tumors, a CXR, bone scan, or PET scan may be performed to see if the

cancer has spread.

CONCOMITANT ORGAN DYSFUNCTION

• Simple nephrectomies performed for secondary hypertension may have significant cardiac impairment related to long-standing increased left ventricle work. • Renal cell cancer may be accompanied by para-neoplastic syndromes, including erythrocytosis, hypercalcemia, and hypertension. • Donor nephrectomies are carefully screened and generally have limited to no organ dysfunction.

TREATMENT PREOPERATIVE PREPARATION Premedications

• No particular preoperative medications indicated • Consider erythropoietin in patients with renal impairment and significant anemia.

Special Concerns for Informed Consent

• For all laparoscopic procedures, patients must be counseled that the risk of conversion to open is approximately 5%. • If an epidural is planned, consent should be obtained in the preoperative area. • Blood transfusion may be needed depending on the patient’s comorbidities, extent of preoperative anemia, and expected duration of surgery. Antibiotics/Common Organisms

• A single preoperative dose of a first-generation cephalosporin is adequate for the majority of nephrectomies. • If the procedure is performed for chronic infection, coverage for Gram-negative anaerobic organisms is needed. INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia is required for either laparoscopic or open approach. • Combined general and epidural anesthesia may be beneficial for open approach. Assess case for possible use of cardiopulmonary bypass (tumor involving vena cava) prior to epidural placement. Anticoagulation needed for pump is a contraindication to CPB. – Epidural or spinal anesthesia requires a T8 dermatome level. Monitors

• An arterial line can be used in the setting of concomitant organ dysfunction, partial nephrectomy, or other renal procedure where large blood loss is anticipated. • A central line allows for determination of central venous pressure (CVP), which can be used to guide fluid management and administer vasopressors or fluid resuscitation if indicated. • Foley catheter to monitor urine output

Induction/Airway Management

IV induction is most commonly performed except in pediatric patients. Maintenance

• Inhalation agent of choice • Cisatracurium is the neuromuscular blocker of choice in the setting of renal insufficiency as it is not dependent on renal function for elimination.

Extubation/Emergence

Ensure adequate pain control and hemodynamic stability prior to extubation

POSTOPERATIVE CARE BED ACUITY

• Floor bed is appropriate for the majority of patients. • A monitored or ICU bed may be necessary in patients with multiple medical comorbidities, significant intraoperative blood loss, or other intraoperative complications.

ANALGESIA

• Open procedure: Epidural, unless contraindicated • Laparoscopic procedure: IV analgesics • Morphine has an active metabolite that is renally cleared. Therefore, it may accumulate in renal insufficiency and cause respiratory depression.

COMPLICATIONS

• Laparoscopic approach ranges from ~8–17%, compared to an open approach of ~2–4%. – Renal failure – Hemorrhage – Infection – Nerve injury – Positioning injury – Diaphragmatic injury, with subsequent pneumothorax requiring chest tube placement

PROGNOSIS

• Dependent on indication for procedure • Patients undergoing nephrectomy for a tumor have a prognosis dependent on the type and stage of cancer as well as medical comorbidities. • Patients undergoing a simple donor nephrectomy are usually healthy and young with an excellent postoperative prognosis.

REFERENCES

1. Demyttenaere S, Feldman LS, Fried GM. Effect of pneumoperitoneum on renal perfusion and function: A systematic review. Surg Endosc. 2007;21(2):152–160. 2. Han KR, Kim HL, Pantuck AJ, et al. Use of American Society of Anesthesiologists physical

status classification to assess perioperative risk in patients undergoing radical nephrectomy for renal cell carcinoma. Urology. 2004;63(5):841–846. 3. Richstone L, Montag S, Ost MC, et al. Predictors of hemorrhage after laparoscopic partial nephrectomy. Urology. 2011;77(1):88–91. 4. Richstone L, Seideman C, Baldinger L, et al. Conversion during laparoscopic surgery: Frequency, indications and risk factors. J Urol. 2008;180(3):855–859. See Also (Topic, Algorithm, Electronic Media Element) • Laparoscopy • Hypertension • Epidural

CODES ICD9 V59.4 Kidney donors ICD10 Z52.4 Kidney donor

CLINICAL PEARLS

• Anesthetic plan is highly dependent on the indication for the procedure and the approach to nephrectomy. • For partial nephrectomy, it is important to have adequate IV access since resection of the lesion may lead to significant blood loss over a short period of time.

NEUROFIBROMATOSIS (NF) Christine E. Goepfert, MD, PhD, DESA

BASICS DESCRIPTION

• Neurofibromatosis is a genetically inherited or sporadic, progressive phakomatosis; it affects neuroectodermal tissues (skin, nerves, eye) with a speckled distribution (phakos = speckle, lens). • There are 3 main types: – NF-1 (von Recklinghausen disease): “Peripheral”; most common – NF-2 (bilateral acoustic or central neurofibromatosis): “Central” – Schwannomatosis EPIDEMIOLOGY Incidence

• NF-1: 1:2,500 to 1:3,000, mean onset 42 years old; most common form, comprising up to 90% of all cases • NF-2: Birth incidence 1:25,000–50,000, annual incidence; mean onset 24 years old • Schwannomatosis: Rare, 1:1.7–2.1 million

Prevalence

• Approximately 100,000 Americans • NF-1: 1:4–5,000 • NF-2: 1:210,000 and higher

Morbidity

NF-1: Varies between no substantial problems other than cutaneous neurofibromas and mild cognitive impairment to severe neurologic deficits and malignancies. The majority of patients have a benign disease. Mortality

• Malignancies limit lifespan • Arterial hypertension from renal artery stenosis or pheochromocytoma is associated with premature death. ETIOLOGY/RISK FACTORS

• Autosomal-dominant with 100% penetrance, but variable expressivity • New mutations comprise 50% of cases.

PATHOPHYSIOLOGY

• NF-1: Mutation of chromosome 17q11.2 leads to reduced neurofibromin. Neurofibromin acts

as a tumor suppressor, and thus inhibits a cellular proto-oncogene p21 ras and activates mTOR, a serine/threonine kinase which regulates cell growth. Thus, NF-1 is characterized by uncontrolled tumor formation that affects the skin and nerves, and is also associated with a high likelihood of malignancies, macrocephaly, and short stature. • NF-2: Mutation of chromosome 22q11–q13 leads to a defect in the product merlin, also known as schwannomin. Merlin acts as a tumor suppressor gene, the function of which is not fully understood. NF-2 is characterized by bilateral acoustic neurinomas (schwannomas), leading to hearing loss, often at a young age. Patients are also at an increased risk for meningiomas and ependymomas. • Schwannomatosis: Mutation of the INI1 gene. There is no clear pattern of inheritance. It can skip generations.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperative assessment is of utmost importance to recognize relevant conditions: – Respiratory compromise may result from upper airway lesions, cranial and cervical nerve fibroma, and thoracic deformities. Additionally, obstruction of conducting airways can result from mediastinal, tracheal, and bronchial fibromas, as well as lung fibrosis and chest wall deformities. – Airway obstruction/compromise may occur secondary to macroglossia, macrocephaly, mandibular abnormalities, and cervical spine involvement. – Pheochromocytoma: May be undiagnosed and can result in death. Baseline arterial blood pressure elevation, even in young patients, should alert the anesthetists of this potential. • If regional anesthesia is considered, assess eligibility clinically and with radiologic evaluation, preferably through thoracolumbar MRI to rule out neuraxial lesions.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Varies greatly between individuals and type of neurofibromatosis • Stridor, difficulty swallowing, throat pain, and changes in voice may suggest airway involvement.

History

Careful assessment of organ involvement Signs/Physical Exam

• See “Concomitant Organ Dysfunction” • NF-2: Bilateral vestibular schwannomas (cranial nerve VIII), leading to deafness; meningiomas, gliomas, neurofibromas

TREATMENT HISTORY

• No specific medical treatment is available. • Surgery for corresponding tumors

MEDICATIONS

Depending on organ involvement, patients may be on antiepileptic, cardiac, or pain medications. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC with platelet count • Coagulation studies • CXR and possibly thoracic CT in case of respiratory compromise • Potentially imaging via CT or MRI, if regional anesthesia considered • Cardiac investigations if required

CONCOMITANT ORGAN DYSFUNCTION

• Central nervous system: – Hydrocephalus due to aqueduct stenosis – Epilepsy – Syringomyelia – Cognitive impairment, ADHD – Cerebral gliomas • Peripheral nervous system: – Deafness – Optic glioma – Polyneuropathy • Skin: – Café-au-lait patches – Multiple cutaneous or subcutaneous tuberous neurofibromas – Plexiform neurofibromas (hallmark lesion) in 30% of patients; they are often large and disfiguring, with malignant progression in 2–16%. – Lisch nodules (iris hamartomas seen on split lamp examination) are present in 95% of patients. – Skin-fold freckling, e.g., axilla, groin, in 70% • Airway: – Intraoral lesions (tongue, larynx) may render intubation difficult; it is seen in <5% of cases. It usually occurs in areas most rich in terminal nerve plexuses. – Involvement of the cervical region and parapharyngeal space may distort the airway. • Respiratory system: – Fibrosing alveolitis – Intraoral, tracheal, or bronchial neurofibromas • Skeleton: – Macrocephaly – Pathologic fractures, especially of the tibia – Scoliosis; thoracic curvatures are seen in 10% of patients and kyphoscoliosis in 2%. This may cause ventilation difficulties and respiratory failure due to reduced lung volume; increased risk for pneumothorax with insertion of the subclavian CVL; and potential problems with positioning for intubation and surgery.

– Short stature at 10th–25th percentile – Bony dysplasia (sphenoid wing dysplasia, bowing of long bone +/– pseudarthrosis of tibia) – Compression of the spinal cord with spine deformities, instability of cervical spine • Vascular: – Generalized vasculopathy – Arterial hypertension (seen in 6% of patients) is due to catecholamine-secreting nodular plexiform neurofibroma, pheochromocytoma, or renal artery stenosis. – Fibrosing alveolitis in approximately 20% – Coronary vasospasm – Aneurysms • Malignancies with NF-1: – Pheochromocytoma is seen in approximately 1% of patients. – Cancerous tumors (e.g., gliomas) are seen in 2% of patients, CML, GI tumors (especially duodenum, carcinoids). • Hematologic: – Benign polycythemia – NF-1 related coagulopathy has been described in case reports; responds to DDAVP. • Psychiatric diseases: – ADHD – Cognitive impairment, especially learning disabilities • Other (NF-1): – Bladder outflow obstruction – Cardiac hypertrophy and outflow obstruction in 2% of patients, especially pulmonary stenosis and ventricular failure

CIRCUMSTANCES TO DELAY/CONDITIONS

• Acute cardiovascular decompensation • Untreated pheochromocytoma, requiring surgery and/or pretreatment with alpha-blockers

CLASSIFICATIONS

• NF-1: Most common, also known as von Recklinghausen disease; affects the “peripheral” system • NF-2: Also known as bilateral acoustic or central neurofibromatosis; affects the “central” system • Schwannomatosis

TREATMENT PREOPERATIVE PREPARATION Premedications

No particular considerations; however, in patients with airway involvement, administer sedatives with caution and monitoring, or avoid altogether, if appropriate.

Special Concerns for Informed Consent

If regional anesthesia, risks and benefits need to be discussed at length. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia is typically the preferred method: Inhalational or intravenous techniques are both feasible. • Neuraxial anesthesia is not contraindicated, but requires very careful assessment and consideration, since at least 2/3rd of patients have spinal neuromas and intracranial lesions. Lumbosacral imaging (e.g., with MRI) may exclude possible spinal tumors. Additionally, tumors in NF-1 are often highly vascular, thus increasing the risk for epidural hemorrhage and dural puncture. Kyphoscoliosis may render spinal or epidural anesthesia impossible. Consider the use of small-bore, atraumatic spinal needles (e.g., 27 G). • Peripheral nerve blocks possess an increased risk of neural injury; the use of ultrasound may increase safety.

Monitors

• Standard ASA monitors • Careful monitoring of muscle relaxants, since prolonged muscle blockade has been reported. • Bladder catheterization may be difficult due to ureter obstruction by retroperitoneal neurofibromas.

Induction/Airway Management

• Neurofibromas of the tracheal area are rare, but may be a cause of difficult intubation and loss of the airway. • Fiberoptic examination and potentially fiberoptic intubation or awake tracheostomy in symptomatic patients

Maintenance

• NMBs and suxamethonium may have potentially prolonged action, although only described in few case reports. • Kyphoscoliosis may cause difficulties in ventilating the patient. • Plexiform neurofibromas are associated with severe bleeding. In the event of uncontrolled, diffuse, and otherwise unexplained intraoperative hemorrhage, the empiric use of DDAVP should be considered.

Extubation/Emergence

Renal impairment and concurrent medication, e.g., antiepileptic drugs, may interfere with anesthetics or NMBs and delay or fasten emergence.

POSTOPERATIVE CARE BED ACUITY

Usually PACU, unless surgery or certain medical conditions require ICU

MEDICATIONS/LAB STUDIES/CONSULTS Only in case of unexpected events COMPLICATIONS

• Respiratory insufficiency due to scoliosis and fibrosing alveolitis • Bleeding diathesis: Diffuse bleeding is possible despite normal coagulation studies, due to platelet dysfunction. • Difficult or impossible intubation due to large neurofibromas affecting tongue, larynx, and cervical tissues • Higher risk in regional anesthesia with potential nerve injury and bleeding of plexiform neurofibromas • Undiagnosed pheochromocytomas may cause death. • Cranial herniation in case anesthetic management or condition leads to increased ICP if intracranial lesions present, such as labor, increased PaCO2, insufficiently blunted sympathetic response.

REFERENCES

1. Rocco MD, Rosenblatt ML. Ultrasound-guided peripheral nerve block in a patient with neurofibromatosis. Reg Anesth Pain Med. 2011;36(1):88–89. 2. Sakai T, Vallejo MC, Shannon KT. A parturient with neurofibromatosis type 2: Anesthetic and obstetric considerations for delivery. Int J Obstet Anesth. 2005;14(4):332–335. 3. Spiegel JE, Hapgood A, Hess PE. Epidural anesthesia in a parturient with neurofibromatosis type 2 undergoing cesarean section. Int J Obstet Anesth. 2005;14(4):336–339. 4. Richardson MG, Setty GK, Rawoof SA. Responses to nondepolarizing neuromuscular blockers and succinylcholine in von Recklinghausen neurofibromatosis. Anesth Analg. 1996;82:382–385. 5. Moorthy SS, Radpour S, Weisberger EC. Anesthetic management of a patient with tracheal neurofibroma. J Clin Anesth. 2005;17:290–292. 6. Lighthall GK, Morgan C, Cohen SE. Correction of intraoperative coagulopathy in a patient with neurofibromatosis type I with intravenous desmopressin (DDAVP). Int J Obstet Anesth. 2004;13:174–177.

ADDITIONAL READING

• Ferner RE. Neurofibromatosis 1 and neurofibromatosis 2: A twenty first century perspective. Lancet Neurol. 2007;6:340–351. • Hirsch NP, Murphy A, Radcliffe JJ. Neurofibromatosis: Clinical presentations and anaesthetic implications. Br J Anaesth. 2001;86(4):555–564. • Jett K, Friedman JM. Clinical and genetic aspects of neurofibromatosis 1. Genet Med. 2010;12(1):1–11.

CODES

ICD9

• 237.70 Neurofibromatosis, unspecified • 237.71 Neurofibromatosis, type 1 [von recklinghausen’s disease] • 237.72 Neurofibromatosis, type 2 [acoustic neurofibromatosis] ICD10

• Q85.00 Neurofibromatosis, unspecified • Q85.01 Neurofibromatosis, type 1 • Q85.02 Neurofibromatosis, type 2

CLINICAL PEARLS

• Knowledge and careful assessment of relevant concomitant conditions is critical. • In a rare case of airway obstruction, even elective fiberoptic intubation may fail due to distorted anatomy. • If unexpected uncontrolled intraoperative bleeding occurs, DDAVP may rescue the situation. • In parturients, pre-term labor can occur in up to 30% of cases. Additionally, ICP may increase if intracranial tumors are present. Neuraxial anesthesia is possible after careful and thorough assessment and lumbosacral imaging, but should be avoided in NF-1 if imaging studies are not available.

NEUROGENIC PULMONARY EDEMA Keren Ziv, MD Carsten Nadjat-Haiem, MD

BASICS DESCRIPTION

• Neurogenic pulmonary edema (NPE) is an acute, potentially life-threatening complication of significant CNS injury, such as subarachnoid hemorrhage (SAH), prolonged seizures, or traumatic brain injury (TBI). • NPE consists of a marked increase in pulmonary interstitial and alveolar fluid, with resultant dyspnea, tachypnea, tachycardia, basilar rales, copious frothy sputum, possible hemoptysis, and hypoxemia. It usually develops within minutes to hours after injury; however, immediate and late (days) onset has been described. PHYSIOLOGY PRINCIPLES

• The Starling’s equation describes the effects of hydrostatic and oncotic pressures on fluid movement between the intravascular and extracellular compartments. – Capillary hydrostatic pressure: Pressure drives fluid out of the capillary, and is highest at the arteriolar end of the capillary and lowest at the venular end. – Capillary oncotic pressure: Plasma proteins keep/draw fluid into the capillary via osmotic effects. Proteins do not readily cross the endothelial cells and, hence, do not reach equilibrium within the two compartments. Albumin accounts for 70–80% of the oncotic pressure of the plasma. – Transcapillary permeability: Permeability of the vessel wall to water. The capillaries’ semipermeable membrane allows water to pass more freely than protein. If the gaps between the cells of the vessel wall widen, then permeability to proteins increases (results in edema). ANATOMY

• NPE “trigger zones” are located in the: – Hypothalamus – Cervical spinal cord – Medulla. Contains several important centers that are believed to contribute to the pathogenesis of NPE via sympathetic stimulation: Solitary tract, area postrema, medial reticulated nucleus, and dorsal motor nucleus. Perioperative bilateral lesions in the medulla at the solitary tract and at the A1 group of neuroadrenergic neurons can cause hypertension and NPE. PHYSIOLOGY/PATHOPHYSIOLOGY

The exact mechanism is unknown. Increased intracranial pressure (ICP), brain injury, or hemorrhage is believed to cause ischemia or compression of medullary centers; this is

believed to begin a cascade of events that alter Starling’s forces: • Increased pulmonary capillary hydrostatic pressure results in an outward driving force of fluids from the pulmonary capillaries. – The inciting CNS injury sets off a massive sympathetic discharge. This results in systemic arterial hypertension, peripheral vasoconstriction, increased pulmonary artery pressure, and pulmonary vasoconstriction. – The increased myocardial workload (oxygen consumption) can cause deterioration of cardiac function. Decreases in left ventricular function can lead to increased left atrial pressures with resultant pulmonary edema. • Increased pulmonary artery permeability is a key step preceding NPE. – Hemodynamic-independent: Some studies suggest that adrenergic activation increases pulmonary vessel permeability. Epinephrine and norepinephrine can have: Direct effects that increase vascular permeability Indirect effects by stimulating secondary mediators which increase the vascular permeability, such as histamine or bradykinin – Hemodynamic-dependent: The “Blast theory” proposed by Theodore and Robin in 1975 states that a severe rise of pulmonary capillary pressure causes increased pulmonary vascular permeability, causing a shift of intravascular volume from the high-resistance systemic circulation to the low-resistance pulmonary circulation. Microvascular injury may be caused by excessive pulmonary vasoconstriction; the consequent increase in vascular permeability results in edema. • Capillary oncotic pressure: The increased permeability allows for passage of proteins through the capillaries, which then exert oncotic pressure and draw fluid out of the capillaries. Studies have shown that the alveolar fluid of patients who have developed NPE has a similar protein concentration to plasma.

PERIOPERATIVE RELEVANCE

• Patients who develop NPE have a very poor prognosis. – Associated with a 60–100% mortality – Reflects the severity of the underlying etiology; thus, an ominous sign – One retrospective study of 680 postmortem deaths from non-traumatic intracranial hemorrhage showed that pulmonary edema was seen in approximately 75% of cases. • NPE may result from several types of cerebral lesions; the most common are: – Fatal subarachnoid hemorrhage: seen in 70% of patients – Status epilepticus: seen in 30% of patients – Traumatic brain injury: seen in 50% of patients • Presentation: – Immediately (minutes to hours); most common – Delayed (days) is also seen; less common • Associated with hemodynamic and cardiac abnormalities: – Neurogenic shock – Left ventricular failure; usually transient and reversible – Elevated troponin level; does not necessarily indicate permanent myocardial injury • Chest radiography:

– Pulmonary infiltrates; maybe in a “butterfly” pattern – Cardiac silhouette is usually normal. • Differential diagnosis includes: – Aspiration pneumonia – Cardiac dysfunction: Often NPE with cardiac changes is erroneously attributed to coronary disease. ECG and enzyme levels are not useful in distinguishing between myocardial infarction and neurologic etiology of cardiopulmonary dysfunction, as they may be abnormal in both entities. The transient nature of NPE helps distinguish between neurologic and cardiac origins. – Acute respiratory distress syndrome (ARDS) • Treatment – Underlying neurologic injury. Because overall outcome is dependent upon the inciting cause, efforts should focus on this. There should be an emphasis on decreasing the ICP. – Supportive treatment consists of supplemental oxygen with or without mechanical ventilation, depending on the severity of hypoxemia. Maintain an oxygen saturation >94%. Implementation of PEEP should be optimized to balance against decreased cerebral venous drainage and worsening of ICP. – Medications: There are few studies that evaluate the efficacy of medications to treat NPE in humans; however, the following may be useful: Beta-adrenergic antagonists may decrease pulmonary capillary permeability but are usually contraindicated in the setting of cardiopulmonary and hemodynamic compromise. Dobutamine may increase cardiac output, counter alpha agonism, and promote diuresis (improved renal perfusion). Steroids have not been tested in humans and may be detrimental. Diuretics should be avoided in the absence of hypervolemia due to the risk of hypotension (can worsen cerebral perfusion pressure). However, mannitol is commonly administered to reduce brain edema, but it has unproven benefits for pulmonary edema. Chlorpromazine, via alpha-adrenergic blockade, has been used in case reports.

EQUATIONS

ADDITIONAL READING

• Ahrens J, Capelle H, Przemeck M. Neurogenic pulmonary edema in a fatal case of subarachnoid hemorrhage. J Clin Anesth. 2008;20:129–132. • Muroi C, Keller M, Pangalu A, et al. Neurogenic pulmonary edema in patients with subarachnoid hemorrhage. J Neurosurg Anesthesiol. 2008;20(3):188–192. • Pender ES, Pollack CV. Neurogenic pulmonary edema: Case reports and review. J Emerg Med. 1992;10:45–51. • Sedy J, Zicha J, Kunes J, et al. Mechanisms of neurogenic pulmonary edema development. Physiol Res. 2008;57:499–506.

See Also (Topic, Algorithm, Electronic Media Element) • Noncardiogenic pulmonary edema • Subarachnoid hemorrhage • Intracranial hypertension

CODES ICD9 514 Pulmonary congestion and hypostasis ICD10 J81.1 Chronic pulmonary edema

CLINICAL PEARLS

• Neurogenic pulmonary edema is an acute complication of severe neurologic perturbation. It is usually self-limited, and mortality is mainly conferred by the underlying neurologic insult. • Treatment is mainly supportive with an emphasis on reducing the intracranial pressure. • Many cases of NPE resolve within days. • There have been recent reports of successful treatment regimens in patients with NPE after SAH: – Immediate treatment of ICP with intubation, sedation, mannitol/hypertonic saline, and, if needed, bolus thiopental – Countering alpha-adrenergic overstimulation with dobutamine

NEUROGENIC SHOCK Keren Ziv, MD Carsten Nadjat-Haiem, MD

BASICS DESCRIPTION

• Neurogenic shock is a type of distributive shock resulting from the loss of sympathetic outflow and unopposed parasympathetic (vagal) nerve activity. • Usually due to a relatively high spinal cord injury (SCI), such as the cervical spine or high thoracic (usually above level T6) vertebrae. It may also result from regional anesthesia (high block). • There is no universally accepted definition of neurogenic shock. Some define it as an SBP <100 mm Hg with an HR <60 bpm, whereas others define it as an SBP <90 mm Hg (1,2). Overall, it is a significantly decreased MAP from baseline value, and is usually symptomatic. • Neurogenic shock differs from spinal shock in that spinal shock is defined as the temporary loss of spinal reflex activity occurring below a total or near-total SCI. The term “shock” is not a description of the circulatory system, but of reflex activity. EPIDEMIOLOGY Prevalence

• 15–52.5 cases per million in the population. 80% males between 15 and 35 years, 5% children (3) • In a recent study of 490 patients presenting with isolated SCI, neurogenic shock occurred with: – Cervical cord injuries: 19.3% (4) – Thoracic injuries: 7% – Lumbar injuries: 3%

Morbidity

• Severe hypotension may result in significant end organ damage to the brain, kidneys, and heart. • Further nerve injury can result from an unstable spine, particularly during intubation.

Mortality

Untreated neurogenic shock may result in death due to organ hypoperfusion. ETIOLOGY/RISK FACTORS

• Severe injury to the CNS: – Brain – Cervical spinal cord – High thoracic spinal cord

• Other causes include: – Spinal anesthesia – Drugs – Emotional stress – Pain – CNS dysfunction

PHYSIOLOGY/PATHOPHYSIOLOGY

• Autonomic nervous system – Parasympathetic nerves have a craniosacral outflow and their preganglionic and postganglionic connections are close to the target organs. Cranial nerves: CN 3, 7, 9, 10 Sacral nerves: S2, S3, S4 – Sympathetic preganglionic neurons have a thoracolumbar outflow. T2-L2 nerves exit the cord via ventral roots and synapse with postganglionic neurons in the paravertebral chain. Cardiac sympathetic neurons are carried from T1 to T4. • Neurogenic shock occurs due to interruption of spinal sympathetic outflow causing loss of vasomotor tone to peripheral arterial beds as well as the loss of compensatory reflex tachycardia. This results in: – Increased venous capacitance – Decreased venous return – Decreased cardiac output – Hypothermia – Warm/dry skin due to the loss of the ability to sweat – Bradycardia (unopposed parasympathetic tone results via the vagal nerve).

PREVENTATIVE MEASURES Prevention of primary injury

PREOPERATIVE ASSESSMENT • Neurogenic shock is a diagnosis of exclusion. • Classic findings are: – Hypotension – Bradycardia – Motor and sensory deficits (corresponding to the level of cord injury) – Warm extremities – Radiologic evidence of vertebral injury – However, only 20% of patients present with classic neurogenic shock symptoms (4). • Diagnosis may be difficult due to associated injuries. A head injury may make motor/sensory assessment impossible, or hypotension may be due to concomitant injury such as bleeding. Thus, prior to making the diagnosis of neurogenic shock, other causes must be sought out.

DIFFERENTIAL DIAGNOSIS

• Concomitant hypovolemic shock from occult bleeding origin in the abdomen, chest, etc. • Isolated head injury causes Cushing’s triad (hypertension, bradycardia, abnormal respiration) as opposed to shock. • Spinal shock is due to the loss of spinal reflex activity below the level of SCI and is not of a circulatory etiology; typically resolves in 3–6 weeks. The term “shock” is a misnomer.

TREATMENT • Adequate IV access and a secure airway are mandatory. Techniques to maintain cervical immobility will likely be necessary if intubation is required. • Monitors. In addition to standard monitors, invasive monitors are usually necessary to aid with management and assess response to therapy (arterial line, central line, pulmonary artery catheter, transesophageal echocardiogram). • Fluid resuscitation is performed to increase the effective circulating blood volume. Transfusion with blood products may be required depending on blood loss. A Foley catheter is placed for loss of bladder function and assessment of volume resuscitation. • Vasopressor support is often required if volume fails to treat hypotension. – Inotropic agents, such as dopamine, dobutamine, and epinephrine, may be added to improve cardiac output and perfusion pressure. – Infusion of an alpha-adrenergic agent (phenylephrine or norepinephrine) or vasopressin may be indicated to provide direct vasoconstriction and thus increase blood pressure. Isolated vasoconstrictive activity has the potential for worsening bradycardia. – In the presence of severe bradycardia, atropine or a temporary pacemaker may be required. • Surgery may be needed to stabilize the spinal cord especially in cases of complete transection or removal of a foreign body. • High-dose steroid administration for SCI is usually center-dependent and discussed with emergency, neurosurgery, or orthopedic personnel.

FOLLOW-UP • Duration is variable and may last hours to weeks. • Recovery is usually incomplete and postural hypotension may persist.

REFERENCES

1. Zipnick RI, Scalea TM, Trooskin SZ, et al. Hemodynamic responses to penetrating spinal cord injuries. J Trauma. 1993;35:578–583. 2. Levi L, Wolf A, Belzberg H. Hemodynamic parameters in patients with acute cervical cord trauma: Description, intervention, and prediction of outcome. Neurosurgery. 1993;33:1007–1017. 3. Grigorean VT, Sandu AM, Popescu M, et al. Cardiac dysfunction following spinal cord injury. J Med Life. 2009;2(2):133–145. 4. Guly HR, Bouamra O, Lecky FE. The incidence of neurogenic shock in patients with

isolated spinal cord injury in the emergency department. Resuscitation. 2008;76:57–62.

5. Piepmeyer JM, Lehmann KB, Lane JG. Cardiovascular instability following acute cervical spine trauma. Cent Nerv Syst Trauma. 1985;2:153–159. See Also (Topic, Algorithm, Electronic Media Element) • Negative pressure pulmonary edema • Total spinal anesthesia • Neurogenic pulmonary edema

CODES ICD9

958.4 Traumatic shock ICD10 T79.4XXA Traumatic shock, initial encounter

CLINICAL PEARLS

• Type of distributive shock resulting in decreased sympathetic tone and unopposed vagal tone causing hypotension and bradycardia • The most common etiology is a high SCI. • May lead to organ hypoperfusion and death • Fluids are the initial treatment; vasopressors may be necessary to maintain hemodynamic stability.

NEUROMUSCULAR JUNCTION Sukhdip Singh, MD Patricia Dalby, MD

BASICS DESCRIPTION

• Neuromuscular junction (NMJ) describes the synapse of the nerve terminal with the muscle membrane. • NMJ is an important site for the action of various drugs. Additionally, it is affected by various diseases, disorders, and pathologic processes. PHYSIOLOGY PRINCIPLES

• Acetylcholine (ACh) is synthesized in the neuron from acetyl coenzyme A and choline by the enzyme choline acetyltransferase and is then packaged into vesicles. • Release of ACh from the nerve terminal: – During a nerve action potential, Na+ channels open and allow for an influx of Na+ with subsequent depolarization of the nerve terminal. – Depolarization of the nerve terminal causes the opening of calcium channels, allowing calcium to enter the nerve. – The influx of Ca2+ mobilizes ACh-containing vesicles to attach to release sites (active zones) on the presynaptic neuronal membrane. – Docking is followed by the release of vesicle content (ACh) into the synaptic cleft. • Generation of a muscle fiber action potential: – ACh diffuses across the synaptic cleft and binds to the acetylcholine receptor (AChR) on muscle cells. – AChR binding opens anion channels, which results in influx of Na+ and Ca2+. – This ion entry generates an end plate potential (EPP). If the EPP is greater than the threshold potential, a muscle fiber action potential is generated leading to muscle cell contraction. • ACh in the synaptic cleft is degraded by the enzyme acetylcholinesterase to terminate the process.

ANATOMY

• A motor neuron divides into multiple branches that lose their myelin sheath before synapsing with the muscle cells. • All of the muscle cells supplied by a single motor neuron form a motor unit. • There is a gap between the nerve terminal and muscle membrane called the synaptic cleft. The postsynaptic membrane has folds or invaginations forming primary and secondary clefts. AChRs are concentrated on the crests of the folds. • The presynaptic nerve ending has membrane thickenings called active zones around which the Ach-containing vesicles are clustered.

• The area of the muscle immediately around the NMJ is the perijunctional zone. • Postjunctional AChRs are of 3 types—mature or junctional type, extrajunctional or immature fetal type, and the neuronal α7 type (1,2).

DISEASE/PATHOPHYSIOLOGY

• The physiologic process of normal neuromuscular transmission is affected by various disorders and pathophysiologic states. • Upregulation of AChRs: Increase in fetal immature type of AChRs occurs within 48 hours of an insult. – Associated conditions include stroke, spinal cord injury, burns, prolonged immobilization, prolonged exposure to neuromuscular blocking drugs, multiple sclerosis, and Guillain– Barré Syndrome. – Immature fetal AChRs are very sensitive to succinylcholine (SCh) and are resistant to nondepolarizing muscle relaxants (NDMRs). Clinical implication: SCh should not be used after 24 hours of an insult. Exposure to SCh causes an increased K+ efflux and hyperkalemia. • Myasthenia gravis (MG): Autoantibodies directed against the postsynaptic AChRs leading to a decreased number of receptors. – Clinical implication: Patients with MG are resistant to SCh, but the response can be unpredictable; patients treated with plasmapheresis or pyridostigmine can have a decreased activity of pseudocholinesterase resulting in potentiation of SCh action. These patients are very sensitive to NDMRs. • Lambert Eaton Myasthenic Syndrome (LEMS): Autoantibodies directed against presynaptic voltage-gated Ca2+ channels resulting in decreased release of ACh at the motor endplate. – Clinical implication: Patients with LEMS are very sensitive to both depolarizing and nondepolarizing muscle relaxants. • Muscular dystrophy: In both Duchenne and Becker muscular dystrophy, there is a defect in dystrophin production leading to absent or abnormal dystrophin. The NMJ has an upregulation of extrajunctional receptors. – Clinical implication: These patients are very sensitive to SCh, which can lead to hyperkalemia and cardiac arrest. Response to NDMRs is variable from normal to increased sensitivity. Although unproven, increased association with malignant hyperthermia and rhabdomyolysis has been suggested. • Myotonic dystrophy: Disorder characterized by delayed or slowing of muscle relaxation following voluntary contraction. This manifests as generalized myotonias and later progresses to muscle weakness and atrophy. – Clinical implication: SCh is contraindicated as it can precipitate myotonic contractions and trismus making endotracheal intubation difficult. Although the response to NDMRs is normal, a reduced dose is required due to underlying muscle wasting. Anticholinesterase medications, such as reversal agents, can precipitate myotonias.

PERIOPERATIVE RELEVANCE

• Neuromuscular monitoring: Assess neuromuscular blockade (NMB) during general anesthesia. – Single twitch: Usually given at 0.1 Hz amplitude every 10 seconds and increased until the

current is slightly greater than that needed for a maximal stimulation. Comparison of twitch height after NMB is then done relative to the maximal twitch height. Useful for establishing the pharmacodynamic properties of an agent but requires a baseline determination of twitch height per individual patient. – Train of four (TO4): 4 stimuli are given at 2 Hz and repeated every 10–12 seconds. The strength of each twitch is equal without NMB, but following NMB administration, there is a decrease relative to the strength of the blockade. The phenomenon occurs because after onset of NMB there is enough ACh available to mount the first twitch but with each stimulus the amount of ACh diminishes. Fade is the phenomenon of the relative decrease of first twitch (T1) to the fourth twitch (T4). A common clinical practice is to compare the strength of the first twitch to the

remaining 3. When there is 90% suppression of the first twitch (T1), only 1 twitch is perceived; at 75% suppression, 3 twitches are perceived. A commonly used clinical correlate is if T4/T1 is approximately 0.75, then an awake

patient can generate a 15 mL/kg vital capacity with an effective cough and sustained head lift. – Double burst stimulation (DBS): 2 short bursts of stimulation that are delivered as 3 stimuli at 50 Hz separated by 750 ms May increase the manual perception of fade because the response to the 3 intense stimuli is felt as one muscle contraction. When fade is present, there is a 75% chance that the TO4 is <0.6, but if there is no fade with DBS then there is a 90% chance that TO4 is ≥0.6. – Tetanic stimulation: 50 Hz for 5 seconds Used clinically with the TO4 to measure the degree of profound muscle relaxation – Post-tetanic count (PTC): Measured with a 1 Hz simulation 3 seconds after tetanic stimulation (50 Hz for 5 seconds) If the PTC is 10, then that is similar to the appearance of T1 or 90% suppression. If there

is no PTC at all, then the NMB is so prolonged that it cannot be reversed reliably. Post-tetanic facilitation occurs because the potent tetanic stimulation causes the increased release of ACh quanta into the synaptic cleft. • Drugs acting on the NMJ: – Depolarizing muscle relaxants: Imitate the action of ACh. Cause sustained depolarization of the motor end plate leading to initial contraction followed by prolonged muscle relaxation. Prolonged administration of SCh can lead to phase II block which has characteristics of NDMR block. – NDMRs: Compete with ACh by preventing ACh from binding to AChRs. Anticholinesterases inhibit the degradation of ACh. The increased concentration of ACh facilitates interaction with AChRs and “reverses" the NDMR block (increases the ratio of Ach to NDMR). – Other medications affecting the neuromuscular transmission include volatile anesthetics, barbiturates, alcohol, cocaine, local anesthetics, aminoglycoside antibiotics,

phenothiazines, and calcium channel blockers. • Neuromuscular disorders: Clinical implications of specific disorders are discussed in “Pathophysiology” section. – These patients are prone to increased cardiac and respiratory depression with anesthetic drugs. – Oropharyngeal muscle weakness, decreased laryngeal reflexes, and prolonged gastric emptying time predispose these patients to increased risk for intraoperative aspiration and postoperative respiratory compromise. – Regional and local anesthesia is preferred. If required, general anesthesia may be maintained with short-acting agents. – SCh should be avoided due to risk of hyperkalemia and malignant hyperthermia. – NDMRs should also be avoided. If muscle relaxation is necessary, short-acting agents, such as mivacurium, should be used.

GRAPHS/FIGURES

REFERENCES

1. Martyn JAJ, Fukushima Y, Chon JY, et al. Up-and-down regulation of skeletal muscle acetylcholine receptors. Intl Anesthesiol Clin. 2006;44:123. 2. Martyn JAJ, Richtsfeld M. Succinylcholine-induced hyperkalemia in acquired pathologic states: Etiologic factors and molecular mechanisms. Anesthesiology. 2006;104:158–169.

3. Fagerlund MJ, Eriksson LI. Current concepts in neuromuscular transmission. Br J Anaesth. 2009;3:108–114.

4. Naguib M, Flood P, McArdle JJ, et al. Advances in neurobiology of the neuromuscular junction: Implications for the anesthesiologist. Anesthesiology. 2002;96:202–231.

5. Shear TD, Martyn JA. Physiology and biology of neuromuscular transmission in health and disease. J Crit Care. 2009;24:5–10. See Also (Topic, Algorithm, Electronic Media Element)

• Duchenne muscular dystrophy • Myasthenia gravis • Myasthenic syndrome

CLINICAL PEARLS

• The most common sites for monitoring of the NMJ during general anesthesia are the ulnar and facial nerves, but other peripheral nerves, such as the median, posterior tibial, and common peroneal, can also be used. • Avoid SCh in patients with neuromuscular disorders and burns status post 24 hours due to the risk of hyperkalemia. • Avoid reversing a phase II block with anticholinesterases as the reversal response can be unpredictable. • Patients taking certain antibiotics, such as aminoglycosides and polymyxin B, may be more sensitive to NDMRs.

NONCARDIOGENIC PULMONARY EDEMA Ravi S. Tripathi, MD Erik E. Abel, PharmD, BCPS

BASICS DESCRIPTION

Noncardiogenic pulmonary edema (NCPE) is caused by one of 2 basic mechanisms: • An imbalance of Starling forces • Lymphatic insufficiency

PHYSIOLOGY PRINCIPLES

• Starling forces: NCPE can result from increased negative interstitial pressure, increased alveolar–capillary membrane permeability, or decreased plasma oncotic pressure. – Increased negative interstitial pressure (Ppmv): Imbalances between intra-alveolar pressure and interstitial or intrapleural pressure can lead to an increased transcapillary pressure gradient causing fluid shift from the microvessels (Pmv) to the perimicrovascular interstitium (Ppmv) with resultant pulmonary edema. – Increased alveolar–capillary membrane permeability (K): Endothelial injury is believed to result from inflammatory processes or sympathetic discharge. It can result in an influx of water, solutes, and macromolecules into the alveoli. – Decreased plasma oncotic pressure (πmv): Occurs in low-protein states such as with hypoalbuminemia in liver disease or critical illness, nephrotic syndrome, or protein-losing enteropathy. Pulmonary edema from decreased oncotic pressure usually involves other exacerbating factors since low-oncotic states alone are typically not sufficient to cause clinically significant presentations. – Increased hydrostatic pressures (Pmv): Involved in the pathogenesis of cardiogenic pulmonary edema. Not commonly a cause of NCPE states. Involved in the pathogenesis of cardiogenic pulmonary edema. However, it may possibly play a role in neurogenic pulmonary edema (NPE) and negative pressure pulmonary edema (NPPE). • Lymphatic insufficiency: NCPE can occur from blockage of lymphatic drainage, which is usually related to either fibrotic disease or inflammatory disease but can also be seen after lung transplantation. PHYSIOLOGY/PATHOPHYSIOLOGY

• NCPE results in: – Increased interstitial hydrostatic pressure – Increased interstitial oncotic pressure – Atelectasis with decreased functional residual capacity – Decreased PaO2, with an increased A-a gradient and a/A ratio

– Decreased pulmonary compliance – Increased work of breathing (in the spontaneously ventilating patient)

• NPPE or postobstructive pulmonary edema has been shown to occur in up to 1/1,000 patients receiving general anesthesia. It requires 2 entities: A negative intrathoracic pressure and a pathological state that prevents the intra-alveolar pressure to accommodate the gradient (obstruction). The increased intrapleural pressure transmits to the alveoli which draw fluid from the pulmonary capillaries into the interstitial space and ultimately the alveoli. On a more global scale, this acute derangement increases venous return and left ventricular afterload, which can potentially favor edema secondary to hydrostatic forces. It can occur: – Post-extubation: Accounts for approximately 74% of all perioperative NPPE. It can result from either laryngospasm or occlusion of the endotracheal tube (e.g., biting the airway conduit), as well as bronchospastic disease. – Initial airway management: Usually seen in patients with head and neck tumors, but also with laryngospasm and epiglottis-induced obstruction. – Airway collapse: Seen with obesity and obstructive sleep apnea; can cause ongoing airway obstruction and subacute or chronic NPPE. – Surgical procedures: An airway procedure such as tracheal dilation can result in complete airway obstruction while the patient remains spontaneously breathing. – Pneumothorax: A sudden release can generate sufficient negative interstitial pressure to generate pulmonary edema (usually unilaterally). • Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): These entities are the end-result of a multitude of disease processes that result in alveolar–capillary membrane injury from inflammatory processes. They are often classified as direct or indirect. – ALI is determined by a chest radiograph with bilateral infiltrates, a normal capillary wedge pressure or lack of evidence for cardiogenic failure, and a PaO2/FiO2 (P/F) ratio

<300. ARDS is a more severe form of ALI with a P/F <200. – Direct lung injury can result from pneumonia/pneumonitis, inhaled toxins, and aspiration. Ventilator-induced lung injury (VILI) must also be considered. – Indirect lung injury can result from shock, sepsis, trauma, and transfusion-related ALI. Although a component of pulmonary edema seen after cardiopulmonary bypass may be due to alveolar–capillary membrane injury, the mechanism and etiology are not completely understood. • Lymphatic insufficiency: In the perioperative period, NCPE may be seen in patients after lung transplant. • Neurogenic pulmonary edema: The pathogenesis is not completely understood. Theories include: – Massive sympathetic discharge that increases hydrostatic pressures secondary to systemic hypertension, peripheral vasoconstriction, increased pulmonary artery pressure, and pulmonary vasoconstriction. – Increased pulmonary artery permeability from direct or indirect effects of epinephrine and norepinephrine: Indirect effects may involve the secondary release of histamine or bradykinin. • Drug-induced: Pathogenesis is not completely understood. – Narcotic overdose with heroin is the most frequent offending agent; however, parenteral and intravenous forms of other legal preparations have also been associated with NCPE.

– Cocaine – Chemotherapeutic agents including cytarabine, recombinant IL-2, all-trans-retinoic acid, arsenic trioxide, mitomycin plus vinblastine, and intrathecal methotrexate (1) • Anaphylaxis can result in increased alveolar–capillary membrane injury. Common perioperative offenders include neuromuscular blocking agents, antibiotics, latex, and anesthetics.

Pregnancy Considerations

• Pulmonary edema can result from: – Severe preeclampsia: It is a defining criterion to separate severe preeclampsia from mild disease. – Noncardiogenic causes (decreased oncotic pressure, increased pulmonary capillary permeability) combined with increased intravascular hydrostatic pressure. Usually develops 2–3 days postpartum. Treatment is mostly supportive, including supplemental oxygen, fluid restriction, and diuretic therapy, but may also require mechanical ventilation with tracheal intubation. Pulmonary artery catheterization may optimize therapy. – Cardiogenic etiologies: An echocardiogram may aid with diagnosis. – Amniotic fluid embolus; usually accompanied with hemodynamic collapse (2).

PERIOPERATIVE RELEVANCE

• Pulmonary edema in the perioperative period can present with hypoxia, rales, frothy sputum, and increased peak and plateau airway pressures. The clinical scenario must always be taken into account, and cardiogenic pulmonary edema should be excluded (acute left heart dysfunction, arrhythmias). • NPPE: The clinical scenario is usually airway obstruction (stridor, wheezing, and inability to ventilate) in a patient who is able to generate high-negative intrathoracic pressure (e.g., young, healthy, athletes who are American Society of Anesthesiologists physical status categories I and II). – Obstruction can also occur in patients with foreign body aspiration, oropharyngeal tumors, and postoperative residual curarization leading to upper airway obstruction. – Intubation may be required but simple measures, such as the application of positive pressure in laryngospasm and bronchodilator therapy in patients with acute asthma exacerbations, may alleviate the underlying process. – After establishing a patent airway, treatment is largely supportive as symptoms usually resolve within 24 hours. – Diuretic therapy is controversial since the primary offense is not intravascular hypervolemia. Additionally, these patients may be intravascularly euvolemic or hypovolemic, and diuretic therapy could lead to further deterioration via hypovolemic shock. • Anaphylaxis may present as wheezing, hypotension, and shock. – Treatment is supportive and aimed at removing the offending agent. – Epinephrine is the primary pharmacologic agent for anaphylactic shock (0.2–0.5 mg every 5 minutes as needed). Histamine blockers (diphenhydramine, famotidine, ranitidine) are also beneficial.

– Measurement of tryptase and histamine levels can help in the diagnosis of an anaphylactic process; however, its clinical effects are not immediate. • ALI/ARDS: Compared with NPPE and anaphylaxis, ALI tends to develop over hours to days but progresses rapidly. – Of all treatment options studied, the only modality that has been demonstrated to reduce mortality is ventilation with low-tidal volumes of 6 mL/kg predicted body weight (3). Other lung protective ventilation strategies include low inspiratory pressures (goal plateau pressure <30 cmH2O), moderate positive end-expiratory pressure, and permissive hypercapnia in addition to lower tidal volumes (5). – In the absence of shock, a fluid-conservative strategy is favored (5). – Perioperatively, inhaled nitric oxide, inhaled epoprostenol, glucocorticoids, highfrequency oscillatory ventilation, and extracorporeal life support offer strategies to improve oxygenation (5). • Neurogenic pulmonary edema treatment is aimed at decreasing intracranial pressure in addition to supportive therapy. Diuretic therapy could be deleterious if it results in hypotension and impaired cerebral perfusion pressures. • Opioid overdose: Naloxone has not been shown to hasten recovery, and supportive therapy remains the mainstay of treatment.

EQUATIONS

Starling equation: Q = K [(Pmv – Ppmv) – (πmv – πpmv)], where • Q = Net transcapillary flow of fluid • K = Transcapillary permeability • Pmv = Hydrostatic pressure in microvessels • Ppmv = Perimicrovascular interstitium

• πmv = Plasma protein oncotic pressure in the peripheral vessels

• πpmv = Protein oncotic pressure in the perimicrovascular interstitium

REFERENCES

1. riasoulis E, Pavlidis N. Noncardiogenic pulmonary edema: An unusual and serious complication of anticancer therapy. Oncologist. 2001;6:153–161.

2. Gist RS, Stafford IP, Leibowitz AB, et al. Amniotic fluid embolism. Anesth Analg. 2009;108:1599–1602. 3. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New Engl J Med. 2000;342:1301–1308. 4. Schultz MJ, Haitsma JJ, Slutsky AS, et al. What tidal volumes should be used in patients without acute lung injury? Anesthesiology. 2007;106:1226–1231. 5. Diaz JV, Brower R, Calfee CS, et al. Therapeutic strategies for severe acute lung injury. Crit Care Med. 2010;38:1644–1650.

ADDITIONAL READING

• Krodel DJ, Bittner EA, Abdulnour R, et al. Case scenario: Acute postoperative negative pressure pulmonary edema. Anesthesiology. 2010;113:200–207. See Also (Topic, Algorithm, Electronic Media Element)

• Alveoli • Acute respiratory distress syndrome (ARDS) • Negative pressure pulmonary edema • Neurogenic pulmonary edema • Anaphylaxis

CODES ICD9 514 Pulmonary congestion and hypostasis ICD10 J81.1 Chronic pulmonary edema

CLINICAL PEARLS

• Noncardiogenic pulmonary edema (NCPE) arises from a number of etiologies, and prompt attention should be given to identifying the underlying causes with a focus on diagnosing life-threatening sources rapidly. • Once a diagnosis is made, appropriate therapy can be instituted; most treatments for NCPE include airway management, supportive care, and removal of the offending agent. • In patients with acute lung injury and acute respiratory distress syndrome, adapting lung protective ventilation is important to decrease mortality and morbidity.

NON-INVASIVE BLOOD PRESSURE (NIBP) CUFF Viachaslau Barodka, MD

BASICS DESCRIPTION

• The non-invasive blood pressure (NIBP) cuff provides an indirect estimation of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and pulse pressure (PP). • Readings are based on the pulsatile phenomena of blood ejection into the systemic arteries and generation of changing pressure (pulse wave) within the arterial tree during the cardiac cycle. PHYSIOLOGY PRINCIPLES

• Auscultatory technique: Based on the auscultation of Korotkoff sounds; normally, blood flow in arteries is laminar and does not produce sound, whereas turbulent flow does. – The inflated cuff causes mechanical constriction and deformation of the artery. – When the cuff pressure is >SBP, the artery is completely occluded during the whole cardiac cycle and no sound is produced. – When the cuff pressure is DBP, turbulent flow occurs. Appearance of the first sound during cuff deflation indicates SBP. – When the cuff pressure is
– Rheology: Viscosity affects the SVR; thus increases in viscosity also increase the SVR and BP. – Because BP is dependent on both CO and SVR, MAP can serve as a surrogate to assess these factors and what comprises them (volume status, contractility, heart rate, presence of perfusing rhythms). MAP is of special importance since it is the perfusion pressure. MAP can be estimated using the following formula: MAP = 1/3 SBP + 2/3 DBP.

ANATOMY

• Position: The NIBP cuff is placed over the upper or lower extremity; the readings record pressures in the brachial or femoral artery, respectively. The “bladder” should be over the artery (so that excessive external pressure is not needed to compress the artery), and ideally the lower edge of the cuff should be approximately 2 cm above the antecubital fossa (to avoid artifacts from bending at the elbow). • Level in relation to the heart: The extremity should be at the heart level for accurate measurements. If the extremity is below the heart level, it will falsely elevate the BP. If the extremity is above the heart level, it will falsely decrease the BP. To correct for this, add or subtract 0.7 mm Hg for each cm that the cuff is above or below the level of right atrium. • Size: Should match the extremity size to measure the BP accurately. – The cuff’s bladder width should be ~40% of the circumference of the extremity to provide adequate occlusion of flow. – The cuff’s bladder length should be ~60% of the extremity (e.g., upper extremity: shoulder to the elbow; lower extremity: knee to the ankle) to provide adequate occlusion of flow. – BP will be falsely high if the cuff is too small for the size of the extremity or when the cuff is applied too tightly. It does not adequately disperse the pressure over the arterial surface. – BP will be falsely low if the cuff is too large for the size of the extremity or when cuff deflations are too quick. Pressure is spread over too large an area and produces a damping effect on the oscillometric pulses.

DISEASE/PATHOPHYSIOLOGY

• Because BP is dependent on both CO and PVR, MAP can also serve as a surrogate to assess PVR and factors that constitute CO (volume status, contractility, heart rate, presence of perfusing rhythm). • Low BP states – Decreases in SVR Anesthetic agents (vasodilation) Sepsis Neurogenic shock Anemia Allergic reactions Severe hypoxia and acidosis Hypocalcemia Arteriovenous malformation with shunt – Reduced CO

Negative inotropes Ischemia Infarction Aortic stenosis Reduced preload (hypovolemia, increased venous capacitance, decreased LV compliance, obstruction such as tamponade) Tamponade Arrhythmias • High BP states – Increases in SVR Sympathetic stimulation Vasopressor administration Pain Hypothermia Coarctation of the aorta Application of a cross-clamp over major central arteries – Increased CO Sympathetic stimulation Pain Positive inotropes Increased preload from hypervolemia Increased heart rate • Decreases in either SVR or CO can be compensated by increases in the other, thus maintaining the same MAP. For example, in patients with cardiomyopathy and low CO, PVR is increased to maintain MAP. In septic patients with low PVR, CO increases to normalize MAP.

PERIOPERATIVE RELEVANCE

• Cuff-based NIBP continues to be the standard method used in the perioperative settings. It has the benefit of being non-invasive, as its name suggests, as well as provides an estimate of overall hemodynamic function. Limitations: – “Snapshot” of the dynamic and pulsatile circulation. Does not provide beat-to-beat readings. – Obesity: The conical shape of an extremity can result in uneven dispersion over the arterial surface. – Shivering can interfere with oscillatory measurements. – Hypotension: At low BP, oscillatory measurements may not be easily detectable by the cuff and transducer. – Arrhythmias can prevent oscillatory measurements. • Under resting conditions in adults, the normal SBP is 90–120 mm Hg and the DBP is 60–80 mm Hg. An adequate MAP is needed for optimal perfusion of vital organs (brain, heart, kidney); however, normal BP values, by itself, cannot assure adequate perfusion. Example: Low CO and tissue perfusion in the face of a high SVR and normal MAP. • High BP exerts additional afterload on the LV, leads to increased LV O2 consumption, and

may precipitate an ischemic episode. Additionally, it can increase perioperative bleeding and may result in hemorrhagic stroke or rupture of an aortic aneurysm. Even mild elevations in BP may be lethal in patients with aortic dissections.

EQUATIONS

• MAP = 1/3 SBP + 2/3 DBP; where MAP is the mean arterial pressure, SBP is the systolic blood pressure, and DBP is the diastolic blood pressure • MAP = CO × SVR; where CO is the cardiac output and SVR is the systemic vascular resistance

REFERENCES

1. Ramsey M. Blood pressure monitoring: Automated oscillometric devices. J Clin Monit. 1991;7(1):56–67. 2. Stokes DN, Clutton-Brock T, Patil C, et al. Comparison of invasive and non-invasive measurements of continuous arterial pressuring using the Finapres. Br J Anaesth. 1991;67(1):26–35. See Also (Topic, Algorithm, Electronic Media Element) • Cardiac output • Afterload • Vascular compliance • Perioperative hypertension

CLINICAL PEARLS

• The NIBP cuff is a standard ASA monitor; it provides an assessment of overall hemodynamic function. • Limitations of the NIBP include: – Inability to detect beat-to-beat pressures – Inaccuracy at low pressures – Requires appropriate cuff/bladder size selection – Decreased accuracy or inability to measure pressures during arrhythmias, movement, shivering

OBESITY HYPOVENTILATION SYNDROME (OHS)/PICKWICKIAN SYNDROME Menelaos Karanikolas, MD, MPH

BASICS DESCRIPTION

• Pickwickian syndrome, also known as obesity–hypoventilation syndrome (OHS) most commonly occurs in patients with obstructive sleep apnea (OSA). However, in 10% of cases, it can occur alone. OHS is characterized by: – Daytime chronic hypercapnia (arterial CO2 tension >45 mm Hg)

– Obesity (BMI >30) – Increase in PaCO2 >10 mm Hg from awake supine values and/or oxygen desaturation

(secondary to hypercapnea) during sleep that cannot be explained by apneic or hypopneic events. • Symptoms often overlap those of OSA: Dyspnea, daytime somnolence, and possibly right heart failure (1). • OHS patients have abnormal medullary respiratory center control; specifically, they lack a compensatory increased ventilatory drive to offset the effects of the mechanical restrictions of obesity. • The name “Pickwickian” comes from a character (a “fat boy” who is constantly falling asleep) in “The Posthumous Papers of the Pickwick Club” by Charles Dickens. EPIDEMIOLOGY Prevalence

Associated with obesity; therefore, the incidence and prevalence of OHS are expected to rise as the prevalence of obesity increases (2)[B].

Prevalence

• 10–15% of patients with obstructive sleep apnea (OSA) develop OHS. • Between 1986 and 2000, the number of individuals with BMI >40 increased 4-fold in the US. Morbidity

Increased risk for hypoxemia, pulmonary hypertension, cor pulmonale, systemic hypertension, and coronary artery disease Mortality

The 18-month mortality among hospitalized patients with OHS is significantly higher (23%) compared to obese patients without OHS (9%) (3)[B].

ETIOLOGY/RISK FACTORS

• Obesity • Obstructive sleep apnea • Gender is not a risk factor.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Obstructive sleep apnea results from excessive/redundant airway tissue that causes a variable, extrathoracic obstruction to air flow. During sleep and in the supine position, the negative inspiratory pressures are more likely to cause these tissues to collapse, whereas during exhalation, the positive pressures “push aside" the tissue. This results in hypoxic events (chronic hypoxia can increase pulmonary artery pressures, polycythemia), increased catecholamines (hypertension, arrhythmias), and poor sleep quality (daytime somnolence, fatigue). It has a significant association with obesity, but may occur in other circumstances such as enlarged tonsils. Although the majority of OHS patients have concurrent OSA (90%), it can occur in isolation; thus although they commonly overlap, they are clinically distinct. • The precise mechanism of OHS is unknown, but is believed to result from a combination of: – Impaired respiratory mechanics (manifests as a restrictive ventilatory defect). Total lung capacity, vital capacity, and compliance are decreased, whereas residual volume, work of breathing (O2 consumption, CO2 production), and airway resistance are increased (1). – Abnormal medullary respiratory center control. OHS patients appear to lack a compensatory increased ventilatory drive to offset the effects of the mechanical restrictions of obesity. On the other hand, obese patients (without OHS) demonstrate an increased ventilatory response. Studies have suggested that OHS patients have a leptin deficiency or resistance. Leptin is normally produced by adipose tissue and acts on the central respiratory center to stimulate ventilation (4)[A].

Anesthetic GOALS/GUIDING Principles

• Perioperative care of patients should focus on maintaining appropriate CO2 levels to avoid a

“relative" respiratory alkalosis. Concurrent management also requires addressing and managing comorbid issues of obesity (BMI >30) and typically obstructive sleep apnea (present in 90% of patients with OHS). • During induction and emergence, position the patient in an upright position (reverse Trendelenburg) to improve respiratory mechanics and facilitate endotracheal intubation. • Use short-acting anesthetic drugs. Benzodiazepines, opioids, and intravenous and inhalational agents that affect the hypoxic and hypercarbic drive may have more profound effects on patients with OHS. • Opioid-sparing techniques for analgesia should be considered (local infiltration, regional or neuraxial blockade). • Postoperative rehabilitation, mobilization, and physical therapy. Postoperatively, consider prolonged observation in the recovery room, or admission to the hospital and continuous pulse oximetry.

PREOPERATIVE ASSESSMENT

SYMPTOMS

• Due to reduced mobility, cardiac disease may remain asymptomatic for years. • Edema and dyspnea on exertion are common and nonspecific.

History

• OHS is under-diagnosed and undertreated. Therefore, morbidly obese patients should be asked about snoring, fatigue, somnolence, or morning headaches that are suggestive of OSA. • Previous anesthesia and hospitalization records • Tobacco, alcohol, and drug abuse can aggravate chronic hypoventilation. • Duration: The risk of cardiomyopathy increases steeply after 10 years of symptoms.

Signs/Physical Exam

• Signs of heart failure (increased jugular venous pressure, hepatomegaly, edema) may be difficult to detect due to excess fat. • Neck circumference >40 cm is associated with OSA. • Pulse oximeter readings can be normal in the presence of hypercapnia.

TREATMENT HISTORY

• Bariatric surgery (malabsorptive, restrictive, or combined) • Home CPAP or BiPAP. Inquire about settings and supplemental oxygen.

MEDICATIONS

• Insulin or oral hypoglycemic for diabetes • Medications for associated cardiovascular conditions • Diuretics for hypertension or edema • Antidepressants • Medications for obesity: Lipase inhibitors (orlistat) or appetite suppressants (rimonabant, sibutramine, phentermine) • Dietary or herbal medications for weight loss

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Serum electrolytes including serum creatinine • Arterial blood gases: Hypercarbia, A-a gradient • EKG to detect ischemia, arrhythmias, atrial or ventricular enlargement • Echocardiography to evaluate myocardial contractility, diastolic dysfunction, right ventricular hypertrophy, pulmonary artery pressures (derived), and valve function; significant tricuspid regurgitation is evidence of pulmonary hypertension. • Routine pulmonary function testing is NOT recommended for preoperative testing. • Formal sleep studies may be needed if the patient’s history is consistent with OHS and there is no established diagnosis. CONCOMITANT ORGAN DYSFUNCTION

• Pulmonary system • Cardiovascular system

• Diabetes mellitus • Musculoskeletal system (arthritis)

Pregnancy Considerations

Epidural analgesia is feasible but technically more demanding. Opioids, (particularly longacting opioids, such as morphine) may have more profound effects on ventilation and oxygenation. CIRCUMSTANCES TO DELAY/ CONDITIONS

Rare, but includes congestive heart failure exacerbation from cor pulmonale

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines and opioids should be cautiously administered with continuous pulse oximetry, even in the holding suite. • Consider H2 blockers, non-particulate antacids, or proton pump inhibitors to reduce the risk of aspiration • DVT prophylaxis

Special Concerns for Informed Consent

• Increased risk for perioperative cardiovascular (myocardial infarction, congestive heart failure, arrhythmias), and pulmonary (aspiration, pneumonia, respiratory failure, respiratory depression) complications. • Regional analgesic techniques, if appropriate

INTRAOPERATIVE CARE Choice of Anesthesia

• Spinal, epidural, and regional anesthesia have been safely performed, but may be technically more difficult. Benefits include avoidance of airway management (bag-mask ventilation and laryngoscopy) and controlled ventilation, as well as a decreased need for opioid analgesics. Drawbacks include inability for an obese patient to tolerate surgical positioning, and failed block or complication that necessitates induction of general anesthesia under suboptimal circumstances. • If general anesthesia is needed, endotracheal intubation with positive pressure ventilation is preferred. Patients have altered chest wall mechanics and response to hypercarbia and hypoxia, as well as decreased functional residual capacity (FRC). Monitors

• Standard ASA monitors • Arterial line may be indicated for monitoring arterial blood gases.

Induction/Airway Management

• Attention to adequate preoxygenation: Morbidly obese patients desaturate quickly due to decreased FRC and increased oxygen consumption. Administering CPAP (6 cm H2O) for 5

minutes while preoxygenating (followed by PEEP after intubation) may be useful in decreasing the level of atelectasis (compared to PEEP alone). • Appropriate positioning: The head and shoulders generally need to be elevated using additional pillows, blankets, or other support material. The head-elevated laryngoscopy position (5)[B] can improve laryngeal exposure during laryngoscopy. • Other general obesity considerations: Consider a rapid-sequence induction due to concerns about aspiration and difficulty with mask ventilation. Prepare for a difficult airway, and consider the use of an indirect video laryngoscopy (6)[B]. Maintenance

• PEEP can decrease atelectasis and increase FRC (decreases V/Q mismatch and increases oxygen storage capacity). • Avoid over-correction of ETCO2 to normal levels. Patients are chronically hypercarbic and

have metabolic compensation (increased HCO3-). Acute decreases can result in an acute

alkalosis. • Inhaled anesthetic agents with low fat solubility (desflurane or sevoflurane) and intravenous propofol infusion are reasonable choices. • Dexmedetomidine can decrease postoperative opioid requirements without causing respiratory depression. • Remifentanil, combined with inhaled anesthetics or propofol, allows for intraoperative analgesia without residual respiratory depression postoperatively. Particularly useful in cases with brief, profound stimulation (e.g., micro direct laryngoscopy).

Extubation/Emergence

• Extubation should be performed in a semi-recumbent position, when the patient is fully reversed and awake. • Consider placing a nasal airway preemptively, to avoid post-extubation airway obstruction, if appropriate.

FOLLOW-UP BED ACUITY

• Resume CPAP or noninvasive positive pressure ventilation • Continuous pulse oximetry • Consider an observation unit or ICU for monitoring

MEDICATIONS/LAB STUDIES/CONSULTS

• Consider postoperative arterial blood gas • Sleep medicine evaluation if OHS diagnosis suspected but not established

COMPLICATIONS

• Cardiovascular: Arrhythmias from respiratory acidosis, myocardial ischemia from hypoxia

• Respiratory: Aspiration, atelectasis, pneumonia, respiratory failure

REFERENCES

1. Piper AJ, Grunstein RR. Current perspectives on the obesity hypoventilation syndrome. Curr Opin Pulm Med. 2007;13:490–496.

2. Flegal KM, Carroll MD, Ogden CL, et al. Prevalence and trends in obesity among US adults 1999–2008. 3. JAMA. 2010;303:235–241. 4. Nowbar S, Burkart KM, Gonzales R, et al. Obesity associated hypoventilation in hospitalized patients: Prevalence, impact, and outcome. Am J Med. 2004;116(1):1–7.

5. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med. 2005;118:948– 956. 6. Levitan RM, Mechem CC, Ochroch EA, et al. Head-elevated laryngoscopy position: Improving laryngeal exposure during laryngoscopy by increasing head elevation. Ann Emerg Med. 2003;41:322–330. 7. Marrel J, Blanc C, Frascarolo P, et al. Video laryngoscopy improves intubation condition in morbidly obese patients. Eur J Anaesthesiol. 2007;24:1045–1049.

ADDITIONAL READING

• Paurier P, Alpert MA, Fleisher LA, et al. Cardiovascular evaluation and management of severely obese patients undergoing surgery: A science advisory from the American Heart Association. Circulation. 2009;120:86–95.

See Also (Topic, Algorithm, Electronic Media Element) • Cor pulmonale • Minute ventilation • Laryngoscopy positioning • Continuous positive airway pressure • Atelectasis

CODES ICD9 278.03 Obesity hypoventilation syndrome ICD10 E66.2 Morbid (severe) obesity with alveolar hypoventilation

CLINICAL PEARLS

• OHS is often unrecognized, but should be considered and suspected in morbidly obese patients, particularly with a diagnosis of OSA.

• Minimize the use of opioid analgesics, if possible, and consider regional analgesia whenever feasible. Have a low threshold for postoperative continuous pulse oximetry. • Postoperative monitoring for apnea

OCULOCARDIAC REFLEX Radha Arunkumar, MD

BASICS DESCRIPTION

• The oculocardiac reflex (OCR) is a trigeminovagal reflex. It was first described in 1908 by Dr. Aschner who observed that the application of pressure on the eyeball resulted in slowing of the heart (1). – The afferent pathway is the ophthalmic division of the trigeminal nerve (CN V), through the Gasserian ganglion, and ending in the trigeminal sensory nucleus in the floor of the fourth ventricle. – The efferent pathway is through the vagus nerve (CN X) to the heart. • Perioperatively, it is most commonly encountered with ophthalmic cases (e.g., pediatric strabismus surgery) due to pressure on the globe or traction of the extraocular muscles. It can also occur: – From orbital floor fractures and neurosurgical procedures involving the trigeminal nerve – After enucleation by stimulation of cranial nerve V in the presence of a tense orbital hematoma – During the performance of a retrobulbar block. Interestingly, retrobulbar blocks may abolish subsequent occurrence. EPIDEMIOLOGY Incidence

Strabismus surgery: 14–90% depending on the premedication, anesthetic agent, and definition of OCR chosen (2)

Prevalence

Can occur in any age group but is more frequent in children and young adults due to their inherent vagal tone Morbidity

There are several case reports of asystole and cardiac arrest in the literature that resulted in successful resuscitation. Mortality

Even though death is very rare, a handful of case reports of deaths with unsuccessful resuscitation have been reported, both directly attributable to OCR and to underlying cardiac disorders such as occult myocarditis. ETIOLOGY/RISK FACTORS • Light general anesthesia

• Stimulus strength and duration • Age (pronounced in children) • Augmented vagal tone • Potent narcotics • Beta-blockers • Calcium channel blockers • Hypoxia • Hypercarbia • Acidosis

PHYSIOLOGY/PATHOPHYSIOLOGY

• A reflex is an involuntary reaction or spontaneous movement to a stimulus; it is mediated via a reflex arch that is comprised of afferent and an efferent limb. The afferent pathway is usually sensory, and the efferent pathway is either motor or autonomic (sympathetic or parasympathetic). • Trigeminal nerve afferent: Pressure on the eye globe or traction of the extraocular muscles returns sensation via trigeminal nerve afferents. – The afferent pathway is through the ophthalmic division of the trigeminal nerve (CN V) ending in the trigeminal sensory nucleus in the floor of the fourth ventricle. • Vagal efferent: The right vagus nerve primarily innervates the SA node while the left vagus nerve primarily innervates the AV node; however, there is a significant overlap in the anatomic distribution. The vagus nerve provides the parasympathetic innervation to the heart, and its actions are mediated by the release of acetylcholine neurotransmitter (binds to cardiac muscarinic receptors) – The most common vagal efferent response is sinus bradycardia. However, junctional rhythm, atrioventricular block, bigeminy, and even cardiac arrest have been reported. – OCR has a very quick onset along with a quick offset when the stimulus is stopped. • OCR is exaggerated by: – Hypoxia, hypercarbia, and acidosis alter the cardiac resting membrane potential and make the heart more susceptible to bradycardia – Augmented vagal tone, especially in children – Potent narcotics: Through their inhibitory action on the sympathetic nervous system – Beta-blockers: Reduce the sympathetic response of the heart thereby augmenting the vagal cardiac response – Calcium channel blockers: Cause peripheral vasodilatation which exaggerates the bradycardia and hypotension

PREVENTATIVE MEASURES

• Gentle surgical manipulation and minimizing mechanical stimulation are believed to be more effective in preventing OCR than other techniques. • Avoid hypoxia, hypercarbia, acidosis, and light general anesthesia. • Pretreatment with atropine or retrobulbar block has not been shown to be effective prophylaxis. • Effects of different anesthetic regimens on the incidence of OCR have been studied during pediatric strabismus surgery.

– Ketamine infusion without volatiles has been found to have the most hemodynamic stability compared to propofol infusion and volatile agents (2,3)[A]. – Propofol or remifentanil anesthesia has been associated with a higher incidence of OCR during strabismus surgery compared to sevoflurane or desflurane anesthesia (4)[A]. – No difference has been found between desflurane and sevoflurane (5)[B].

DIAGNOSIS • ECG: Sudden onset of sinus bradycardia that is defined as a 10–20% decrease in resting heart rate that is sustained for 5 seconds or longer • Pulse oximetry: Correlating pulse will decrease or be dampened. • Blood pressure: Hypotension

DIFFERENTIAL DIAGNOSIS

Inadvertent anticholinergic administration

TREATMENT • Vigilant intraoperative monitoring is important because the reflex ceases when stimulation stops. • Inform the surgeon; discontinuing stimulation is the first step in treating OCR. • Sustained and repeated stimulation may cause the OCR to fatigue. • Persistent bradycardia is treated with IV atropine or glycopyrrolate; if the patient remains unresponsive, epinephrine administration may be necessary. • Local injection of lidocaine near the eye muscle or peribulbar/retrobulbar block with local anesthetic may be needed. Local anesthetics interfere with excitation and conduction of action potential in the nerves by blocking the voltage-gated sodium channel; this blocks the afferent limb of the reflex arc.

REFERENCES

1. Dewar KM, Wishart HY. The oculocardiac reflex. Proc R Soc Med. 1976;69(5):373–374. 2. Hahnenkamp K, Honemann CW, Fischer LG, et al. Effect of different anaesthetic regimes on the oculocardiac reflex during paediatric strabismus surgery. Paediatr Anaesth. 2000;10(6):601–608. 3. Mizrak A, Erbagci I, Arici T, et al. Ketamine versus propofol for strabismus surgery in children. Clin Ophthalmol. 2010;4:673–679. 4. Choi SR, Park SW, Lee JH, et al. Effect of different anesthetic agents on oculocardiac reflex in pediatric strabismus surgery. J Anesth. 2009;23(4):489–493. 5. Oh AY, Yun MJ, Kim HJ, et al. Comparison of desflurane with sevoflurane for the incidence of oculocardiac reflex in children undergoing strabismus surgery. Br J Anaesth. 2007;99(2):262–265.

ADDITIONAL READING

• Arasho B, Sandu N, Spiriev T, et al. Management of the trigeminocardiac reflex: Facts and own experience. Neurol India. 2009;57:375–380.

See Also (Topic, Algorithm, Electronic Media Element) • Bradycardia • Retinal detachment

CLINICAL PEARLS

• OCR is iatrogenic and most commonly occurs during pediatric strabismus surgery due to traction of extraocular muscles. • The afferent pathway is the ophthalmic division of the trigeminal nerve; the efferent pathway stems from the vagus nerve. • Sinus bradycardia is most common, but other dysrhythmias including cardiac arrest can occur. • Discontinuing surgical stimulation is key to management of OCR. • Premedication is not helpful, but IV treatment with atropine or glycopyrrolate should be administered if bradycardia is persistent.

OMPHALOCELE John T. Chalabi, MD Swati Patel, MD

BASICS DESCRIPTION

• Omphalocele is a midline abdominal wall defect. The herniated viscera is covered by a membrane that consists of: – Peritoneum on the inner surface – Amnion on the outer surface – Wharton’s jelly between the layers (1) • It results due to the failure of the bowel to return to the abdominal cavity after physiologic midgut herniation (PMH) that occurs during the 6th–10th week of gestation. • The defect is typically identified on prenatal ultrasound (after the 12th week of gestation). • Omphalocele commonly contains small intestine and liver; however, large intestine, bladder, spleen, stomach, uterus, and ovaries can also be present in the defect (2). • The physiologic impact is based on the size of the defect and associated anomalies. Bowel function is usually preserved. However, there is a high incidence of associated congenital anomalies (see Concomitant Organ Dysfunction). • Surgical management: – Staged silo repair: Spring-loaded versus stitched (with gradual reduction of abdominal contents over 7–10 days) – Primary closure is performed for smaller defects. – Delayed closure (months later) is performed for giant omphaloceles. EPIDEMIOLOGY Prevalence

Ranges between 1.5 and 3 per 10,000 births (1)

Prevalence

• The Office of Rare Diseases (ORD) of the National Institutes of Health (NIH) lists the omphalocele as a “rare” disease, affecting <200,000 people in the US. • Male-to-female ratio is 1:1.

Morbidity

• In the absence of other major anomalies, the rate of long-term morbidity is about 20%. • Major complications include: – Respiratory failure – Failure to thrive – Intestinal ischemia/obstruction, short gut syndrome – Wound infection and dehiscence

Mortality

In the literature, a 61% mortality is reported for omphalocele with associated anomalies, in contrast to <15.5% in those without (3).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintain adequate ventilation • Maintain hemodynamics and avoid hypovolemia • Prevent trauma to the herniated viscera • Maintain normothermia • Correct hypoglycemia

PREOPERATIVE ASSESSMENT SYMPTOMS

• Range from none to severe respiratory and/or hemodynamic shock; depends on the size of the hernia, concomitant diseases, and neonatal reserve. • Gastroesophageal reflux (GERD) is not uncommon.

History

• Size of the omphalocele • Mode of the delivery (vaginal, cesarean, etc.) • Any concomitant disease/syndromes • Hemodynamic stability and volume status • Acid–base status and potential lung disease associated with prematurity or hypoplasia

Signs/Physical Exam

• Membrane-covered defect ranging in size from 2 to 15 cm. • Respiratory: Look for signs of respiratory distress (patients with large defects are often intubated in the delivery room). • Cardiovascular: Look for signs of hemodynamic instability secondary to hypovolemia (weak pulses, poor distal extremity perfusion) or loud murmurs and decreased oxygen saturation suggesting the presence of congenital heart disease

MEDICATIONS

• Broad spectrum antibiotics • Total peripheral nutrition (TPN) • H2 receptor blockers

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC, electrolytes, blood glucose, coagulation studies, type and cross, and blood gas • Chest radiograph and echocardiogram

CONCOMITANT ORGAN DYSFUNCTION

• Chromosome anomalies, notably trisomy 13, 14, 15, 18, and 21, are present in up to 30% of cases. • Cardiac defects are common; they are seen in 30–50% of cases. • Neural tube defects are present in up to 40% of patients with omphalocele. • Beckwith–Wiedemann syndrome is seen in 10% of patients. It presents as macroglossia, organomegaly, early hypoglycemia (from pancreatic hyperplasia and excess insulin), and an increased risk of Wilms’ tumor, hepatoblastoma, and neuroblastoma developing later in childhood. • Pentalogy of Cantrell presents with omphalocele associated with ectopia cordis, anterior diaphragmatic hernia, defect of the pericardium and various congenital intracardiac anomalies, and defects of the lower sternum. • Organ dysfunction associated with prematurity, if present

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Unlike gastroschisis defects, the bowel is completely covered by a sac that protects it from infection and large insensible fluid losses. This allows time for: – Thorough assessment of comorbidities prior to surgical repair – Correction of hemodynamic instability • Large defects (giant omphalocele), if reduced quickly, may lead to ventilatory compromise, impede venous return, and cause aortocaval compression from direct compression (abdominal compartment syndrome). These defects may take several months to reduce/repair. CLASSIFICATIONS

Omphaloceles are categorized as: • Small (<2 cm) • Medium (2–5 cm) • Giant (6 cm and bigger)

TREATMENT PREOPERATIVE PREPARATION Premedications Not anticipated

Special Concerns for Informed Consent

• Risks particular to associated anomalies, if present. • Need for continued postoperative intubation

INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia with endotracheal tube is the anesthetic technique of choice. Monitors

• Standard ASA monitors: A pulse oximeter above and below the diaphragm should be placed. • Monitor for significant increases in peak inspiratory pressure (PIP), reductions in tidal volume (TV), or oxygen desaturation throughout the abdominal closure. These abnormalities may indicate that the primary closure will not be tolerated. • Consider invasive monitoring as necessary: – Arterial catheter for hemodynamic and blood gas monitoring if respiratory problems are anticipated (large defect, pulmonary hypoplasia, etc.) or if the patient has congenital heart disease or cardiovascular instability. – +/– CVP – Foley catheter

Induction/Airway Management

• Decompress the stomach prior to performing a rapid-sequence induction • Choice of induction agents should be based on hemodynamic status and any coexisting cardiac conditions. • Care with (or avoidance of) bag-mask ventilation to avoid bowel distention • The endotracheal tube size should be chosen to allow high-pressure ventilation if necessary.

Maintenance

• Typically opioid and volatile agents are utilized. However, the choice of agents should be tailored to comorbid conditions, as appropriate. • Muscle relaxation to facilitate abdominal relaxation • Nitrous should be avoided as it may cause bowel distention and difficulty with reduction of the hernia. • Avoid hypothermia: Warm fluids, place a full body warmer, warm the room • If on TPN, decrease to 1/2 maintenance and monitor for hypoglycemia • Fluid requirements can be up to 50–200 mL/kg/hr depending on the extent of bowel involvement and exposure. Large fluid requirements must be balanced with any coexisting heart disease.

Extubation/Emergence

• Most patients will remain ventilated postoperatively. • May consider extubation postoperatively in patients with small defects. – Consider size of patient, comorbidities, hemodynamic stability

FOLLOW-UP BED ACUITY NICU

MEDICATIONS/LAB STUDIES/CONSULTS As indicated

COMPLICATIONS

• Respiratory failure/compromise

• Pulmonary edema • Hemodynamic collapse • Electrolyte imbalance • Infection: GI (necrotizing enterocolitis), peritonitis wound, pulmonary, etc. • Abdominal compartment syndrome • Hypertension secondary to decreased renal perfusion • Postoperative ileus requiring prolonged TPN (less common than with gastroschisis)

REFERENCES

1. Ledbetter DJ. Gastroschisis and omphalocele. Surg Clin North Am. 2006;86(2):249–260.

2. Frolov P, Alali J, Klein MD. Clinical risk factors for gastroschisis and omphalocele in humans: A review of the literature. Pediatr Surg Int. 2010;26(12):1135–1148.

3. Henrich K, Huemmer HP, Reingruber B, et al. Gastroschisis and omphalocele: Treatments and long-term outcomes. Pediatr Surg Int. 2008;24(2):167–173.

ADDITIONAL READING

• Brusseau R, McCann ME. Anaesthesia for urgent and emergent surgery. Early Hum Dev. 2010;86(11):703–714.

See Also (Topic, Algorithm, Electronic Media Element) • Gastroschisis • Hypothermia • Insensible fluid losses

CODES ICD9 756.72 Omphalocele ICD10 Q79.2 Exomphalos

CLINICAL PEARLS

• Assess for associated anomalies (chromosomal, congenital heart disease, neural tube defects) • Adequate volume resuscitation should take place prior to surgical repair

ONE LUNG VENTILATION Daniel Castillo, MD Sascha Beutler, MD, PhD

BASICS DESCRIPTION

• One lung ventilation (OLV) is achieved by isolating either the right or left lung in order to: – Isolate ventilation in the case of a bronchopleural fistula or to protect the healthy lung from pus, blood, other fluids, or protein in the affected lung – Facilitate surgery/exposure by collapsing one lung while the other lung sustains ventilation and gas exchange during the procedure • Lung isolation can be achieved by 3 basic methods (1,2,3)[B]. – Placing a right or left endobronchial double lumen tube (DLT) – Placing a single lumen endotracheal tube in conjunction with a bronchial blocker (Arndt, Cohen, balloon-tipped luminal catheters) or utilizing a commercially available endotracheal tube with a built-in blocker (Univent) (4,5,6)[B] – Placing a single lumen tube in the right or left main bronchus • Lung isolation can also be done through a tracheostomy tube and is most commonly done with a bronchial blocker (3)[B].

PHYSIOLOGY PRINCIPLES

• Ventilation (V) and perfusion (Q): The relationship between V and Q determines gas exchange, with the ideal V/Q ratio being 1; however, there are physiologic regional differences. – Alveolar lung units are said to “shunt” when V < Q, whereas “dead space” results when V > Q. – Lung base: V and Q are highest in this “dependent area” when standing up. However, perfusion is proportionally greater than ventilation (V < Q), creating a shunt. – Mid-lung (Zone 2): V and Q decrease at different proportions, resulting in ventilation and perfusion matching (V = Q). – Apices: V and Q continue to decrease at different proportions, resulting in ventilation exceeding perfusion (V > Q) and creating dead space. – At any given time, shunting and dead space occur in different areas without derangements in oxygenation or CO2 removal. Thus, V/Q matching must be understood on a spectrum

based upon the number of units with mismatch, as well as the lung’s ability to compensate (distal units able to upload O2 and dispose of CO2, hypoxic pulmonary vasoconstriction

[HPV], and supplement O2).

• Bilateral ventilation with general anesthesia, different ventilatory modes, lateral position, and an open chest – Spontaneous ventilation: Anesthetic agents (volatile and intravenous) decrease the

functional residual capacity by impairing diaphragmatic and intercostal muscle function. This results in cephalad movement of the abdominal contents and decreased chest wall expansion. This increases the number of atelectatic alveolar units (V = 0). – Lateral position: The upper lung (non-dependent) has increased compliance since the abdominal pressure is mostly exerted over the lower lung (dependent and lower compliance). Perfusion remains gravity-dependent and preferentially flows to the dependent lung. – Positive pressure ventilation (PPV) and muscle paralysis: Although PPV can improve V/Q matching by overcoming the abdominal pressure on the diaphragm, the non-dependent areas are preferentially ventilated while the dependent areas are preferentially perfused. – Open chest: Exposing the non-dependent lung to atmospheric pressure increases its compliance and PPV is preferentially diverted. However, perfusion remains gravitydependent and preferentially flows to the dependent lung. • OLV: When ventilation only occurs to one side, any blood flow to the non-ventilated lung becomes shunt flow (V < Q). This results in a large alveolar–arterial oxygen gradient and decreased PaO2. Factors that aid with redistribution of pulmonary blood flow to the dependent lung help to maintain PaO2 in an acceptable range during surgery. Despite the

effect on PaO2, it has much less effect on PaCO2. The ventilated lung is able to compensate by eliminating a higher amount of CO2 to compensate for OLV (provided that minute

ventilation is maintained). – Spontaneous ventilation: In addition to the non-dependent lung being shunted, cephalad movement of abdominal contents will also increase the number of atelectatic units in the dependent lung. – PPV aids with offsetting the effect of the abdominal contents to the dependent, ventilated lung. – Lateral position: Blood that flows to the non-dependent lung is shunted (there is no ventilation). Gravity shifts the blood flow towards the dependent and ventilated lung. Maneuvers that “shift" blood flow to the non-dependent lung will therefore worsen shunting. – Open chest: Exposure of the pleural cavity to atmospheric pressure on the surgical side will help initiate collapse of the non-ventilated lung, as well as further shift/defer perfusion to the dependent lung. • HPV: A physiologic response by pulmonary capillary vessels to low oxygen tension in the alveoli. Vasoconstriction occurs, decreasing blood flow to the alveoli and diverting blood to ventilated alveoli. By optimizing blood flow, the end result is a decrease in shunting. ANATOMY

• The lungs are contained in the chest cavity, which is formed by the rib cage, the diaphragm, and chest muscles. Parietal pleura lines the inside of the rib cage. • Each lung is surrounded by its own visceral pleura. The intrapleural space is a potential space that lies between the parietal and visceral pleura has a negative pressure that “brings" together or “sucks" the two surfaces towards each other. • The tracheobronchial tree starts with the trachea and divides in a dichotomous fashion,

ending in alveolar sacs. • The trachea is about 11–13 cm long in an adult, starts at the cricoid cartilage, and first divides/bifurcates at the level of T5 (carina) to form the right and left main stem bronchus. • The right bronchus is wider, diverges from the trachea at a 25° angle and branches into the upper, middle, and lower lobes. The right upper lobe branches at approximately 1–2.5 cm distal to the carina. • The left bronchus diverges from the trachea at a 45° angle and branches into an upper and lower lobe. The left upper lobe diverges approximately 5 cm distal to the carina. • Because of these differences, right and left DLTs are slightly different in their endobronchial lumen design. Right DLTs have a side opening (Murphy’s eye) close to the tip and surrounded by the cuff so that it can be positioned at the right upper lobe origin to assure its ventilation; the cuff of a left DLT may inadvertently block the right main bronchus (2,7) [B].

DISEASE/PATHOPHYSIOLOGY

• OLV is indicated: – In massive hemorrhage or infection to isolate the lungs and avoid spillage and dissemination of infection – To control distribution of ventilation; bronchopleural fistulas, surgical opening of conductive airway, tracheobronchial tree disruption, severe hypoxemia due to unilateral lung disease – Exposure for surgical procedures: Aortic surgery, spine surgery, lung resection, esophageal surgery, single lung transplantation, and thoracoscopy among others • Pulmonary circulation has much less smooth muscle to control tone than systemic circulation; therefore, any increase in pulmonary arterial pressure (mitral stenosis, congestive heart failure, thromboembolism) can recruit and dilate pulmonary vessels and potentially interfere with HPV. Other mechanisms that have been traditionally attributed to interfere with HPV are direct vasodilating drugs (nitroglycerin, nitroprusside, etc.) and volatile anesthetics.

PERIOPERATIVE RELEVANCE

• Prior to the initiation of OLV for surgical procedures, the patient’s comorbidities should be assessed and optimized to decrease morbidity (cardiac function, pulmonary hypertension, chronic obstructive pulmonary disease, coagulopathy). • Initiation of OLV. Ventilation should be adjusted properly to minimize hypoxia. – Start by ventilating both lungs with tidal volumes of 6–8 mL/breath, a normal I:E ratio, a rate of 8–10/min, and 100% FIO2. The goal is to observe the peak and plateau airway pressures. – Upon instituting OLV, adjust the respiratory rate according to the PaCO2 without changing

the tidal volume. – If the peak and plateau pressures do not increase by >5–8 mm▒Hg, maintain the same tidal volume; otherwise, decrease tidal volume so that the airway pressure is maintained within the above-mentioned range. – Increase the respiratory rate as needed to maintain normocarbia; keep in mind that this

can indirectly increase airway pressures. • Collapsing the non-dependent lung: Exposure of the pleural cavity to atmospheric pressure on the surgical side will initiate collapse of the lung. – Accelerated by a higher FIO2 before lung isolation, clearing the airway of secretions, and

applying gentle suction to the non-ventilated lung – Slowed or hampered by small airway diseases, secretions in the airway, tumor pressure on the airway, malpositioning of the DLT, and pleural adhesion and fibrosis • Factors that aid with diverting blood flow and maintaining a PaCO2 in an acceptable range during surgery: – Passive: Gravity (lateral decubitus), pre-existing lung disease (mass), surgical manipulation and interventions (ligation of vessels) – Active (more effective): HPV • Hypoxia: – DLT malposition (major cause): Fiberoptic examination of the tube position is necessary in any patient with OLV and hypoxia; confirm that the tube is not too deep (endolobar) or that the cuff is not herniating upwards into the carina (8)[B]. – Shunting: Interventions to decrease shunting depend upon the severity of hypoxia. If mild, consider starting with continuous positive airway pressure (CPAP) to the non-dependent lung followed by positive end expiratory pressure (PEEP) to the dependent lung (may “shunt” blood to the non-dependent lung and worsen hypoxia). When acute or severe, temporary re-expansion of the non-dependent lung and/or clamping of the pulmonary artery to the non-dependent lung (if surgical conditions permit). – Secretions: Can cause localized hypoventilation, which can be improved by suctioning – Decreased cardiac output: Can impair oxygen delivery to tissues. Increasing the CO may improve hypoxia by improving mixed venous O2. GRAPHS/FIGURES

FIGURE 1. Left-sided double lumen tube. The endobronchial lumen sits in between the carina and left upper lobe. There is an increased margin for error while positioning, and even for right sided lung surgeries and procedures, a left DLT is commonly placed (with ventilation to the left lung/dependent lung through the endobronchial lumen).

FIGURE 2. Right-sided double lumen tube. The endobronchial lumen sits below the carina. However, because of the

shorter distance between the carina and right upper lobe takeoff, there is little margin for error while positioning. In order

to avoid occlusion and shunting of the right upper lobe, a Murphy’s eye is embedded into the endobronchial cuff to allow ventilation. Ventilation also occurs through the endobronchial lumen.

FIGURE 3. Fiberoptic view of a properly positioned left double lumen tube via the tracheal lumen. The carina should be

visualized along with the endobronchial cuff slightly above the bronchial lumen. The posterior tracheal rings can aid with identifying that the view is of the trachea, and not endobronchial.

REFERENCES

1. Koshy T, Nair SG. Positioning of double-lumen endobronchial tubes: Correlation between clinical and bronchoscopic findings. Indian J Anaesth. 2003;47(2):116–119. 2. Campos JH. Current techniques for perioperative lung isolation in adults. Anesthesiology. 2002;97(5):1295–1301. 3. Campos JH. An update on bronchial blockers during lung separation techniques in adults. Anesth Analg. 2003;97:1266–1274. 4. Ransom ES, Carter L, Mund GD. Univent tube: A useful device in patients with difficult airways. J Cardtothorac Vasc Anesth. 1995;9(6):725–727. 5. Campos JH, Kernstine KH. A comparison of a left-sided Broncho-Cath with the torque: Control blocker Univent and the wire-guided blocker. Anesth Analg. 2003;96:283–289. 6. Takenaka I, Aoyama K, Kadoya T. Use of the Univent bronchial-blocker tube for unanticipated difficult endotracheal intubation. Anesthesiology. 2000;93(2):590–591.

7. Kernstine KH. The incidence of right upper-lobe collapse when comparing a right-sided double-lumen tube versus a modified left double-lumen tube for left-sided thoracic surgery. Anesth Analg. 2000;90:535–540. 8. Uwe K, Karzai W, Bloos F, et al. Role of fiberoptic bronchoscopy in conjunction with the use of double lumen tubes for thoracic anesthesia: A prospective study. Anesthesiology. 1998;88:346–350.

9. Campos JH, Massa C, Alliaume B, et al. Reliability of auscultation in positioning of doublelumen endobronchial tubes. Can J Anaesth. 1992;39(7):687–690. 10. Brodsky JB, Lemmens HJ. Left double-lumen tubes: Clinical experience with 1,170 patients. J Cardiothorac Vasc Anesth. 2003;17(3):289–298.

11. Swift J. Placement of double lumen tubes—time to shed light on an old problem. Br J Anaesth. 2000;84(3):308–310. See Also (Topic, Algorithm, Electronic Media Element) • Double lumen tube • Hypoxic pulmonary vasoconstriction

CLINICAL PEARLS

• Correct positioning of a DLT can be confirmed clinically by auscultation of the lungs during manual ventilation; breath sounds should be absent distally when clamping the desired lumen (tracheal, bronchial) (9)[B]. Visualization with a fiberoptic scope is the gold standard for confirming positioning. • Patients with severe restrictive lung disease, very low cardiac output, or pneumonia in nonventilated lung may be less capable of handling the shunt created in the non-dependent lung.

OPERATING ROOM FIRES Jeanna Blitz, MD Shawna Dorman, MD

BASICS DESCRIPTION

• An operating room fire is any fire that ignites in the operating or procedure room. • Anesthesia providers should be aware of the treatment and prevention of surgical and airway fires. – Surgical fires are defined as those that occur on or around a patient. – Airway fires are defined as surgical fires that ignite within the patient’s airway or breathing circuit. • All fires require the triad of an ignition, oxidizer, and fuel. Thus, prevention in high-risk scenarios should aim at reducing or eliminating one of these elements. EPIDEMIOLOGY Incidence

• Difficult to accurately assess because there is no FDA mandate requiring operating room staff to report a fire • In the US, there are approximately 550–650 surgical fires per year. • 21% of surgical fires involve the airway.

Morbidity

Disfiguring or disabling injuries from operating room fires is estimated to occur in 20–30 patients per year (1).

Mortality

Death from operating room fires occur in ~1–2 patients per year (mostly airway fires) ETIOLOGY/RISK FACTORS

• Fire triad – Ignition: Electrocautery, lasers, fiberoptic light source, defibrillators, high-speed burrs – Oxidizers (gases that can support combustion): Oxygen and nitrous oxide – Fuel: Alcohol-based surgical preps, ETT, breathing circuits, drapes, body hair, nasal cannula, face masks, intestinal gases • High-risk surgical procedures are defined as anytime an ignition source may come in close proximity to an oxygen-rich environment. – Procedures above the xiphoid, sedation with open oxygen source (face mask, nasal cannula) Cataract Carotid endarterectomy (cervical block)

Removal of skin lesions Face lifts Blepharoplasty – Procedures that “enter" the airway Tracheostomy Biopsy (vocal cords, tracheal) Removal of lesions Oropharyngeal procedures

PHYSIOLOGY/PATHOPHYSIOLOGY

• Oxygen lowers the temperature at which a fuel will ignite. – Even materials that will not burn in room air will do so in an oxygen-enriched environment. – Oxygen-enriched fires are hotter, more intense, and spread more rapidly. • Oxygen-enriched environments are defined as any atmosphere in which the oxygen concentration is >21% or the partial pressure is >160 mm Hg (2). – Drapes promote trapping or pooling of oxygen from open sources (blow by, face mask, nasal canula). – Airway procedures enter an enclosed, oxygen-enriched environment • Nitrous oxide supports combustion by dissociating and releasing heat and oxygen.

PREVENTATIVE MEASURES

• Most, if not all, operating room, surgical, and airway fires are preventable. • Deliver safe room air sedation. – Select patients with normal pulmonary function – Judiciously administer hypnotics, sedative, and opioids – Use of a pulse oximeter AND end-tidal CO2 to monitor the patient’s oxygenation and

ventilation can decrease hypoxic events by allowing earlier diagnosis of hypoventilation. – Oxygen saturations of 92% can be safe and acceptable; <90% is undesirable because the steep portion of the oxyhemoglobin dissociation curve puts the patient at risk for rapid desaturation. • Maintain supplemental oxygen <30% when administered via an open oxygen source in any head or neck surgery (3)[C]. – Nasal cannula can be used at flow rates <4 L/minute if ignition sources are >10 cm from the oxygen outlet and the head is not draped (2)[C]. – Venturi masks entrain room air to lower the FiO2 that is delivered. – “Blow by" with a hose is used when masks are not appropriate to the clinical situation. The use of a color adapter may be helpful to indicate the FiO2 that is delivered. Confirm

that the device is properly sampling the area exposed to the ignition source. – Air–oxygen blenders are devices that mix medical air and oxygen into a gas source ranging from 21% to 100% oxygen. They are precise and reliable, but not always readily available in the operating room. – In-line oxygen sampling can be utilized to provide a more controlled oxygen delivery system. The connector of a 5.0 ETT can be attached to the Y- piece of a circuit, and the

nasal cannula or face mask can then be connected to it. The pop-off valve needs to be closed completely and fresh gas flows (oxygen and air) can be adjusted accordingly. Be careful not to deliver nitrous oxide. – Adherent tape may be used to isolate the incision from the oxygen-enriched atmosphere. • Maintain a low threshold to convert to general anesthesia if the patient cannot maintain an oxygen saturation >92% with an FiO2 <30%, rather than just increasing the FiO2. An ETT

or supraglottic device will confine enriched oxygen to the breathing circuit and lungs of the patient. • Drapes should not be placed until all flammable preps have dried fully. • Coating hair and facial hair with water-soluble surgical lubricating jelly renders the hair nonflammable. • Bipolar instead of monopolar electrocautery should be encouraged in high-risk surgeries. Bipolar devices create little or no sparking and have not been recorded to start any surgical fires. • Procedures that enter the airway or involve oropharyngeal tissue. Fires may be reduced by: – Placing moistened sponges around tissue and the endotracheal tube. – Using a laser-proof ETT. Polyvinyl chloride tubes can be readily penetrated by a laser to release oxygen within the lumen; additionally, they can burn in oxygen concentrations as low as 25%. Thus, they are considered the least safe option (4)[C]. – Decreasing the FiO2 for 2 minutes prior to entering the airway and flushing air at 5–10 L/min to wash out excess oxygen. – Encouraging surgeons to enter the airway with a scalpel instead of electrosurgery (5)[C]. – Avoiding nitrous oxide.

DIAGNOSIS • Usually obvious with the presence of flames or smoke • Unusual noise or feeling of warmth

TREATMENT • In the event of a surgical fire: – Remove burning material from the patient. Discontinue the flow of all airway gases. – Have another member of the team extinguish the flame. – Assess the patient’s injuries and treat as necessary. – Control any bleeding. – Evacuate the patient if there is danger from the smoke or fire. – Use an aqueous solution to extinguish non-electrical fires. However, the fluid resistance of surgical drapes may not allow water to reach the fire. Use a CO2 fire extinguisher if needed. – Never use a fire blanket as this will contain the fire on the patient. • In the event of an airway fire (5)[C]: – First remove the ETT or LMA.

– Turn off the oxygen or nitrous oxide. – Remove the drapes. – Pour saline into the airway to ensure that the fire is extinguished. – Mask-ventilate the patient with air until all sources of fire are suppressed. – Re-secure the patient’s airway. – Inspect the patient for injuries and treat accordingly. Rigid bronchoscopy should be performed after an airway fire.

FOLLOW-UP • Once the fire has been extinguished, evaluate the extent of the fire damage. Discuss with the surgeons whether or not to continue with the case. Each decision should be made based on fire damage, urgency of the surgery, and patient stability. • Maintain a very low threshold of leaving the patient intubated as smoke inhalation injury may have occurred, but edema may be delayed. • If the patient was awake when the fire erupted, he/she may recall the smell of the flames and the resulting pain. Consider psychiatry consult, be empathetic, and explain the event. • Consult the plastic surgeon for the management of skin and airway burns (4).

CLOSED CLAIMS DATA

• ASA currently has only task guidelines; however, there will soon be mandates that everyone must follow. • 17% of anesthetic malpractice claims are related to burns from surgical fires (4).

REFERENCES

1. Yardley IE, Donaldson LJ. Surgical fires, a clear and present danger. Surgeon. 2010;8:87– 92. 2. Orhan-Sungur M, Komatsu R, Sherman A, et al. Effect of nasal cannula oxygen administration on oxygen concentration at facial and adjacent landmarks. Anaesthesia. 2009;64:521–526. 3. ECRI. New clinical guide to surgical fire prevention. 2009;314–329. 4. Nishiyama K, Makiko K, Kodaka M, et al. Crisis in the operating room: Fires, explosions and electrical accidents. J Artif Organs. 2010;13(3):129–133. 5. American Society of Anesthesiologists Task Force on Operating Room Fires. Practice advisory for the prevention and management of operating room fires. Anesthesiology. 2008;108(5):786–801.

ADDITIONAL READING

• Bhananker SM, Posner KL, Cheney FW, et al. Injury and liability associated with monitored anesthesia care: A closed claims analysis. Anesthesiology. 2006;104:228–234. • www.ecri.org See Also (Topic, Algorithm, Electronic Media Element)

• Electrical safety • Airway fires • Thyroidectomy • Cataract • Burr hole • Smoke inhalation injury

CLINICAL PEARLS

• The majority of surgical fires are preventable. • Recognize which surgical procedures are high risk for operating room and airway fires (tonsillectomy, tracheostomy, cataract, creation of burr hole, carotid endarterectomy). • Vigilance is of utmost importance when caring for a patient undergoing a high-risk procedure with a natural airway and open oxygen source. Minimizing or eliminating enriched oxygen delivery is fundamental in preventing fires. • Convert quickly to GA with a secured airway if the patient is not able to tolerate an FiO2 <30%. • Consider the possibility of smoke inhalation injury that can result from thermal injury to the airways, particulate irritation, and gaseous-related injury.

OXYGEN ANALYZERS ON ANESTHESIA MACHINES Laura L. Roberts, MD Julie McSwain, MD, MPH

BASICS DESCRIPTION

• Modern anesthesia workstations include the anesthesia machine, a ventilator, vaporizers, monitors, and alarms; together with the breathing and scavenging system, it constitutes the anesthesia delivery system. To ensure adequate oxygen delivery, several safety mechanisms are built into the system. • The 2 largest manufacturers of anesthesia delivery systems in North America are Drager Medical, Inc. (Telford, PA) and Datex-Ohmeda, a division of GE Healthcare (Madison, WI). Despite differences between the 2 manufacturers, current guidelines mandate the following oxygen safety systems: – Multiple oxygen sources – Oxygen supply and pressure alarms – Inspired oxygen concentration monitor – Hemoglobin oxygen saturation monitor (1,2)

PHYSIOLOGY PRINCIPLES

• Multiple oxygen sources exist including a pipeline, cylinder, and auxiliary supply. • Pipeline supply: – The primary gas source for the anesthesia machine and provides oxygen (and other gases) to the system at approximately 50 psig. – Diameter-Indexed Safety System (DISS) is a specific and nationally standardized, gasspecific, system that ensures appropriate connection of all supply pipelines to the anesthesia machine. It prevents the wrong pipeline attachment and inadvertent delivery of a hypoxic gas mixture. • Cylinder supply: – A backup supply in the event of depleted or malfunctioning pipeline supply – Pin Index System (PIS) is a specific, nationally standardized, pin configuration on the cylinder yoke that corresponds to the appropriate cylinder valve on the machine. It prevents the wrong cylinder from being attached to the wrong valve and inadvertent delivery of a hypoxic gas mixture. • Auxiliary oxygen supply: – Located on the anesthesia machine and can provide supplemental oxygen with a nasal cannula, facemask, or Ambu bag; functions even if the anesthesia machine is off. – There is no oxygen analyzer in this set-up, and a misconnection could result in a hypoxic gas being delivered to the patient from this source. • Preventing the delivery of a hypoxic gas mixture is a major consideration in the design of anesthesia delivery systems. An adequate oxygen supply is ensured via several systems—the

fail-safe valve, the oxygen–nitrous oxide proportioning system, a pressure regulation and threshold system, an oxygen concentration monitor, and an oxygen saturation monitor. • Fail-safe valve: – Located downstream from the nitrous oxide source. Depending on the manufacturer, it has the ability to shut off or decrease the supply of nitrous oxide if oxygen pressure decreases. An oxygen supply failure alarm is also activated. It should be noted that the fail-safe valve operates according to oxygen pressure, not flow. A hypoxic gas can still be delivered if the pressure is unchanged or if a system leak develops distal (downstream) to the fail-safe valve. – In Datex-Ohmeda systems, the fail-safe valve is a pressure sensor shut-off valve (PSSV) that completely stops the flow of nitrous oxide and other gases when oxygen pressure falls below a predetermined threshold of 20 psig. – In Drager systems, the oxygen failure protection device (OFPD) proportionately decreases the flow of other gases as oxygen pressure decreases until a threshold is reached after which gas flow ceases. • Oxygen–nitrous oxide proportioning system: – Ensures that a minimum level of 25% oxygen is flowing when nitrous oxide is used. Since this system is linked only to nitrous oxide, if other gases are used, a hypoxic mixture may be given. – In Datex-Ohmeda systems, the Link-25 Proportion Limiting Control System connects the oxygen and nitrous oxide flow meters via a steel link chain such that as the flow of nitrous oxide increases, so does the oxygen flow. – In Drager systems, an Oxygen Ratio Monitor Controller (ORMC) limits the flow of nitrous oxide with flow resistors and diaphragms according to the flow of oxygen. • Pressure regulation and thresholds: These are designed such that oxygen is the last flow to decrease should a machine failure occur. • Inspired oxygen concentration monitor: – Aids in detecting the delivery of a hypoxic gas mixture (1). It is the only device that confirms the presence of oxygen in the inspired gas mixture. – Depending upon the machine type and manufacturer, the inspired oxygen concentration is measured by an oxygen sensor or analyzer: An oxygen sensor is a galvanic fuel cell located near the inspiratory unidirectional valve. A multi-gas analyzer incorporates a paramagnetic oxygen analyzer and samples gas near the circuit Y-piece. • Pulse oximetry

FIGURE 1. Diagram of a generic 2-gas anesthesia machine.

ANATOMY

• Gases enter the anesthesia system and flow through 3 pressure circuits: High, intermediate, and low (3). • High-pressure circuit: Consists of the gas cylinders and their primary pressure regulators – E cylinders for oxygen and nitrous oxide are initially 2,200 and 745 psig, respectively, and are downregulated to provide gases at approximately 45 psig. • Intermediate pressure circuit: Consists of the regulated pipeline/cylinder supplies to the flow control valves – In most Datex-Ohmeda machines, a second stage regulator further decreases oxygen pressure to a range of 12–19 psig and nitrous oxide to 26 psig. • Low-pressure circuit: Consists of the flow control valves to the common gas outlet – The oxygen flow meter is typically downstream of all other gases because in the event of a flow meter leak, a hypoxic gas mixture is least likely (but not prevented) with this configuration.

DISEASE/PATHOPHYSIOLOGY

• Numerous situations can occur that may lead to an inadequate oxygen concentration. These include: – A hypoxic gas delivered from the oxygen pipeline or tank – A disconnection of the fresh gas hose with use of a hanging bellows ventilator – Oxygen flow control valve turned off – Malfunction of the fail-safe system – Failure of the nitrous oxide-oxygen proportioning system

– An oxygen leak in the low pressure system – Use of inadequate oxygen flow rate with a closed circuit (4) • While adverse outcomes related to gas delivery equipment are rare, the associated injuries can be severe. In one review of claims between 1961 and 1994, gas delivery equipment problems accounted for 2% of all equipment-related adverse events, 72 of 3,791 claims. However, death or brain damage was the result in 76% of these claims (5).

Recommended Essential Steps in a Pre-Anesthesia Checkout Procedure. Feldman JM, Olympio MA, Martin D, Striker A. New guidelines available for pre-anesthesia checkout. APSF Newsletter. 2008;23:6–7.

Recommended Essential Steps in a Pre-Anesthesia Checkout Procedure.

Feldman JM, Olympio MA, Martin D, Striker A. New guidelines available for pre-anesthesia checkout. APSF Newsletter.

2008;23:6–7.

• With improved monitoring devices and additional safeguards on modern systems, adverse events have decreased. In a more recent review of claims the reported number and severity of adverse events related to anesthesia gas delivery equipments decreased to 1% and 30%, respectively (4).

PERIOPERATIVE RELEVANCE

• In order to ensure the proper function of the anesthesia delivery system and decrease the risk for a serious adverse event, equipment checklists have been developed and modified over the last several decades: – The 1993 Food and Drug Administration (FDA) Anesthesia Apparatus Checkout Recommendations (6). This checklist is most often used and contains 14 items that should be completed prior to initial machine use and can be abbreviated between anesthetics (7). – The 2008 Recommendations for Pre-Anesthesia Checkout Procedures (8). These are new guidelines developed to address changes in anesthesia workstations and contain 15 items applicable to all modern anesthesia systems. The initial machine check can also be abbreviated between anesthetics (8). • Regardless of which list is used, the most important preoperative checks are: Oxygen analyzer calibration, low-pressure circuit leak test, and circle system test. • Oxygen analyzer calibration: – One of the more important monitors on the anesthesia machine because it is the only device that evaluates the function of the low-pressure circuit and detects problems downstream of the flow meters. – It should read 21% with room air and 90% or greater when the system is flushed with oxygen. – The low oxygen concentration alarm should be enabled. • Low-pressure circuit leak test: – A test for leaks is essential to ensure system integrity because the components in the lowpressure circuit are quite susceptible to breakage and leaks, and the low-pressure circuit is downstream from all safety devices except the oxygen analyzer. – Methods for testing the low-pressure circuit vary between manufacturers. – In general, the presence or absence of a check valve near the common gas outlet greatly influences which method is used. Most Datex-Ohmeda systems have this check valve and are tested with a negativepressure leak test using a suction bulb. Drager machines do not have a check valve and are tested with a positive-pressure leak test with flow from the anesthesia machine or a bulb. • Circle system test: – This test evaluates the integrity of the breathing circuit and the unidirectional valves from the common gas outlet. – Occluding the Y-piece, closing the APL valve then pressurizing and holding the system to 30 cm H2O tests for circuit leaks. Inhaling and exhaling into the appropriate circuit limbs test the function of the unidirectional valves.

REFERENCES

1. Standard Specification for Particular Requirements for Anesthesia Workstations and their Components ASTM F1850-2005. 2. West Conshohocken, PA: American Society for Testing and Materials, 2005.

3. tandards for Basic Anesthetic Monitoring. Park Ridge, IL: American Society of Anesthesiologists, 2010. 4. Check-Out: A Guide for Preoperative Inspection of an Anesthesia Machine. Park Ridge, IL: American Society of Anesthesiologists, Inc., 1987.

5. Eisenkraft JB. Hazards of the anesthesia workstation. ASA Refresh Course Anesthesiol. 2009;37(1):37–55.

6. aplan RA, Vistica MF, Posner KL, et al. Adverse anesthetic outcomes arising from gas delivery equipment: A closed claims analysis. Anesthesiology. 1997;87:741–748.

7. Anesthesia Apparatus Checkout Recommendations. Rockville, MD: US Food and Drug Administration, 1993.Brockwell RC, Andrews JJ. Understanding your anesthesia workstation. ASA Refresh Course Anesthesiol. 2007;35(1):15–29. 8. Feldman JM, Olympio MA, Martin D, et al. New guidelines available for pre-anesthesia checkout. APSF Newsletter. 2008;23:6–7.

ADDITIONAL READING

• Eisenkraft JB. Anesthesia machine basics. Semin Anesth Perioperative Med Pain. 2005;24:138–146.

CLINICAL PEARLS

• Differences exist between manufacturers and models; therefore, it is essential to be aware of the function of the particular anesthesia system in use, including its alarms and safety features. • An anesthesia system pre-use checklist should be completed prior to the use of the anesthesia machine and between anesthetics as necessary. Though equipment checklists are helpful, it is important to remember that they are recommendations and may not contain specific instructions for all anesthesia machines. Anesthesia providers should refer to system manuals for design-specific features. • Backup sources for oxygen and emergency airway equipment must be immediately available should a machine failure occur.

OXYGEN TOXICITY Julie Marshall, MD

BASICS DESCRIPTION

• Oxygen toxicity can result from exposure to high concentrations of inhaled oxygen and is also known as oxygen toxicity syndrome, oxygen poisoning, or oxygen intoxication. It can result from either: – Full body immersion in high oxygen concentration conditions (e.g., hyperbaric chambers) – Inhalation exposure (e.g., mechanical ventilation, prematurity) • High blood partial pressures of oxygen can result in the generation of free radicals that interrupt cellular processes and damage tissue components such as the lungs, central nervous system, and eye. PHYSIOLOGY PRINCIPLES

• Oxygen is an “oxidizing” agent and accepts electrons transferred from other compounds; in doing so, it is “reduced.” This occurs most commonly in the electron transport chain, which couples electron transfer from NADH to oxygen and generates ATP across the mitochondrial membrane. • “Reduced” oxygen forms reactive oxygen species (ROS) that are natural byproducts of oxygen metabolism (i.e., electron binding). Other metabolic pathways that contribute to the formation of ROS include oxidative–reductive processes: Cytochrome P450 activity, nitric oxide synthases, and inflammatory pathways. • ROS play an important role in cell signaling, via a process called oxidative signaling. For example: – Iron uptake occurs via anion exchange protein 2 and is dependent on superoxide anion (O2-). – Hydrogen peroxide modifies cellular function and response to insults. – Platelet recruitment – Apoptosis • ROS are normally buffered by endogenous antioxidants such as superoxide dismutase, catalases, and glutathione peroxidases. Other in vitro antioxidants include Vitamins E and C and uric acid. ANATOMY

• The mitochondria generate most of the ROS in cells as a result of the oxidative–reductive process. • Free radicals may also be generated at other locations in the cell, such as the plasma membrane and cytoplasmic enzyme systems.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Oxygen reduction and the formation of ROS is a normal physiologic function. However, exposure to high concentrations of inspired oxygen can result in excessive production of ROS and overwhelm the native antioxidant supply. • The remaining active free radicals can react with components of the cell, causing cellular damage or dysfunction. Injury to proteins, lipids, or nucleic acids may cause cell death or dysfunction. ROS may also: – Create additional free radical compounds in cells, activating pro-death signals in cells – Inactivate nitric oxide reactions involved in vascular and bronchial responsiveness • Lung damage. The time to clinical emergence is inversely proportional to the FiO2 concentration (higher concentrations contribute to lung pathology at a faster rate) – Acute tracheobronchitis Can occur after 4–24 hours of 95% FiO2 at normal atmospheric pressure; may occur in 3

hours at 3 atmospheres of pressure. May see cough with substernal pain or a burning sensation in the chest Reduction of tracheal mucociliary transport with erythema and swelling of the bronchial lining. Symptoms decrease a few hours after terminating oxygen therapy. Complete resolution of symptoms occurs within days. – Diffuse alveolar damage Usually takes >48 hours of oxygen therapy to develop Similar clinical picture to acute respiratory distress syndrome (ARDS), including reduced pulmonary compliance, increased P(A–a)O2 gradient, decreased vital capacity, and

decreased carbon dioxide diffusion – Pulmonary fibrosis may occur after prolonged ventilation. – Bronchopulmonary dysplasia (BPD) Thought to be caused by direct damage to pulmonary epithelium by ROS The chance of developing bronchopulmonary dysplasia may be increased in premature infants exposed to high oxygen environments. ROS may further impair the development of the premature lung. This may be due to impairment of nitric oxide signaling involved in lung maturation. • Central nervous system toxicity may occur above normal atmospheric pressures, either underwater or in hyperbaric chambers. – Early manifestations include twitching of perioral and hand muscles, as well as cogwheel breathing from diaphragmatic twitching. – Further exposure may lead to vertigo, nausea, behavioral changes, and generalized tonic– clonic seizures. • Eye – Retinopathy of prematurity (ROP) The second most common cause of blindness in children in the US. Premature infants <30 weeks postconceptual age or <1,500 g are at higher risk. ROP is a multifactorial condition; however, hyperoxia plays an important role in development of this condition. Initially, the high oxygen concentration halts growth of vessels in the eye by suppressing vascular endothelial growth factor (VEGF).

As the eye grows, the retina outgrows the blood supply, and the retinal tissues become hypoxic. Abnormal vascular growth occurs in response, eventually leading to vision impairment or blindness. – Reversible myopia Direct oxygen contact with the lens (as in a hyperbaric chamber) can cause local toxic effects on the lens. May also occur, to a lesser extent, from inhalation of high oxygen concentrations. – Cataract formation may occur after repeated hyperbaric oxygen therapies.

PERIOPERATIVE RELEVANCE

• While there is animal data and theoretical concern that high intraoperative FiO2

concentrations may cause lung injury, there is no strong clinical evidence this occurs with routine intraoperative procedures (1)[C]. • Addition of PEEP may improve oxygenation without increasing FiO2 concentrations.

• Patients coming from intensive care units on mechanical ventilation may have lung changes from oxygen toxicity. This may make intraoperative oxygenation and ventilation more challenging. In severe cases of diffuse alveolar damage, using the patient’s intensive care unit ventilator may be advisable. • In patients being treated in the intensive care unit, decreasing FiO2 concentrations may lead

to lower mortality rates (2)[B]. • Cardiopulmonary bypass – Reperfusion injury may occur after cardiopulmonary bypass when the ischemic heart is exposed to high oxygen concentrations. – Exposure of the ischemic heart to hyperoxic conditions may generate oxygen-free radicals and lead to myocardial damage. – Normal oxygen tensions after cardiopulmonary bypass may decrease oxidative myocardial damage (3)[A]. • Bleomycin Risk factors associated with developing lung damage: Pre-existing lung injury from bleomycin Exposure to bleomycin in the last 2 months (4)[C] – If the clinical situation allows, consider administering a low FiO2 (<30%) for anesthesia or intensive care unit ventilation. – There are reports of ARDS following general anesthesia in patients who have a history of bleomycin exposure; however, there is variable evidence for this association in reports (4) [C]. • Amiodarone – It is proposed that exposure to high levels of oxygen therapy and resultant ROS generation may contribute to amiodarone-induced lung injury. – As with bleomycin, exposure to high oxygen concentrations should be avoided if clinically possible. • Premature infants – Limit oxygen concentration to patients <32 weeks postconceptrual age.

– Consider accepting lower SpO2 levels to limit hyperoxia for premature infants (5)[A]. Equations

• PAO2 = PiO2 – (PaCO2/R); where PAO2 is the partial pressure of oxygen in the alveoli, PiO2

is partial pressure of inhaled gas, PaCO2 is the partial pressure of carbon dioxide in the

artery, and R is the respiratory coefficient (normally 0.8). • Alveolar–arterial gradient: PAO2 – PaO2; where PAO2 is the partial pressure of oxygen in the alveoli, and PaO2 is the partial pressure of oxygen in the artery.

REFERENCES

1. night PR, Holm BA. Three components of hyperoxia. Anesthesiology. 2000;93(1):3–4.

2. De Jonge E, Peelen L, Kijzers PJ, et al. Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients. Crit Care. 2008;12(6):R156. 3. hnken K, Winkler A, Schlensak C, et al. Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult. J Thorac Cardiovasc Surg. 1998;116(2):327–334. 4. Mathes DD. Bleomycin and hyperoxia exposure in the operating room. Anesth Analg. 1995;81:624–629. 5. Chen ML, Guo L, Smith LEH, et al. High or low oxygen saturation and severe retinopathy of prematurity: A meta-analysis. Pediatrics. 2010;125(6):1483–1492. 6. Auten RL, Davis JM. Oxygen toxicity and reactive oxygen species: The devil is in the details. Pediatr Res. 2009;66(2):121–127. 7. Bitterman H. Bench-to bedside review: Oxygen as a drug. Crit Care. 2009;13:205.

• Donaldson L, Grant IS, Naysmith MR, et al. Acute amiodarone-induced lung toxicity. Intensive Care Med. 1998;24(6):626–630. • Jackson RM. Pulmonary oxygen toxicity. Chest. 1985;88(6):900–905. • Patel DN, Goel A, Agarwal SB, et al. Oxygen toxicity. J Indian Acad Clin Med. 2003;4(3):234–237. • Waid-Jones MI, Coursin DB. Perioperative considerations for patients treated with bleomycin. Chest. 1991;99(4):993–999.

See Also (Topic, Algorithm, Electronic Media Element) • Retinopathy of prematurity • Atrial fibrillation • Cardiopulmonary bypass • Ciliary function

CODES ICD9

987.8 Toxic effect of other specified gases, fumes, or vapors ICD10 • T41.5X4A Poisoning by therapeutic gases, undetermined, init encntr • T41.5X4D Poisoning by therapeutic gases, undetermined, subs encntr • T41.5X4S Poisoning by therapeutic gases, undetermined, sequela

CLINICAL PEARLS

• Clinical signs of pulmonary toxicity are rarely seen with a routine general anesthetic. • In the intensive care unit, attempts should be made to limit prolonged periods of hyperoxia in order to reduce the chance for pulmonary damage. Alternative ventilation techniques or application of PEEP may assist in minimizing the exposure to high oxygen concentrations. • Keep FiO2 low for premature infants if clinical situation allows, in order to minimize the

contribution to retinopathy of prematurity and bronchopulmonary dysplasia. • The clinical concerns with hyperbaric oxygen therapy include central nervous system toxicity, pulmonary toxicity, reversible myopia, and cataract formation. • If clinically possible, avoid exposing a patient with a history of bleomycin or amiodarone therapy to high oxygen level concentrations.

PACEMAKER DEPENDENT Peter M. Schulman, MD Marc A. Rozner, PhD, MD

BASICS DESCRIPTION

• No universally established definition (1). Pacing dependence can occur in a patient with a conventional pacemaker (PPM) or an implanted cardioverter-defibrillator (ICD). • Indications for pacing (whether a conventional PPM or ICD) include either a slow or inadequate intrinsic rate or the need for profound beta blockade: – Slow or inadequate HR: Sinus node disease, atrioventricular node disease, neurocardiogenic syncope, long QT syndrome – Beta blockade: Tachycardia syndromes, hypertrophic obstructive cardiomyopathy • Indications for biventricular pacing (cardiac resynchronization therapy (CRT)) include cardiomyopathy with a left ventricular ejection fraction ≤35% (2) • Absolute Pacing Dependency (PD) is defined as an absence of intrinsic heart rhythm (asystole) following cessation of ventricular pacing • Functional Pacing Dependency is defined as symptoms resulting from inadequate intrinsic heart rhythm following cessation of ventricular pacing or failure to pace both ventricles correctly in a patient with cardiac resynchronization therapy (CRT) • Preoperatively, the patient with a cardiac implantable electronic device (CIED) will likely require additional information gathering and care to determine current programmed parameters, especially pacing mode and rate. The identification of pacing dependence will alert the perioperative team to the high risk of hemodynamic embarrassment, serious injury, or death from device malfunction or failure. Care should be directed toward minimizing the chance of perioperative electromagnetic interference (EMI), as it can interfere with CIED function, possibly resulting in ventricular over-sensing and pacing inhibition. EPIDEMIOLOGY Prevalence

• Variable and dependent on definition and testing technique used (1) • Increasing yearly in the general population; the adjusted implantation incidence of permanent PPMs has increased 2.7-fold over 30 years (3) • Patients with high-grade AV block (AVB) have a higher incidence of PD than patients with sinus node disease (SND) (4). In older studies, the incidence of PD was 24–50% in AVB and 6–12% in SND. In more recent studies with different diagnostic criteria the incidence was much less (1). • In a recent study, the annual rate of new onset PD in PPM patients was 1.6% (4) • Following cardiac surgery 1–3% of patients need PPMs of which many develop PD (1)

Prevalence

• In PPM patients, the reported prevalence of PD is highly variable with a historical published range from 5–30% • In one recent study, 2.1% of PPM patients were PD, and patients with AV block had a higher prevalence than patients with sick sinus syndrome or atrial fibrillation (AF) (5)

Morbidity

• Impossible to quantify, however, PD might confer increased morbidity (6) • Risk of significant symptoms following an abrupt cessation of pacing, such as profound ventricular bradycardia, hypotension, syncope, inadequate perfusion, death.

Mortality

• Impossible to quantify • Possible association between PD and cardiovascular as well as overall mortality (5,7) • Risk of cardiac arrest following an abrupt cessation of pacing

ETIOLOGY/RISK FACTORS

• Sinus node disease (can include PD) • Advanced heart block (can include PD) • AV node ablation for treatment of drug refractory AF (almost always PD) • Neurocardiogenic syncope (rarely PD) • Cardiac surgery (can include PD) • Previous myocardial infarction (MI) (can include PD) • Temporary pacing prior to permanent pacemaker implant (can include PD)

PHYSIOLOGY/PATHOPHYSIOLOGY

• Pacing systems are comprised of a pulse generator and leads. The pulse generator houses the battery and electronic/computer equipment; it is most frequently implanted in the prepectoral fascia just inferior to the clavicle. Most current systems employ transvenously placed leads which contact the endocardium. The same electrodes are used to sense intrinsic electrical impulses from the heart as well as deliver an electrical stimulus to depolarize the myocardium in the appropriate chamber. The atrial lead is positioned with its tip in the right atrial appendage. The right ventricular lead is positioned with its tip in the right ventricular apex or outflow tract. For biventricular pacing (CRT), a third lead is placed in the coronary sinus to pace the left ventricle. Sometimes, this lead is placed on the epicardium. • Basic settings include: – Pacing mode; denoted by position (8) 1st position: Chamber(s) paced 2nd position: Chamber(s) sensed 3rd position: The response to sensing 4th position: The presence or absence of rate modulation programming 5th position: Multisite pacing, if present – Lower rate – Upper tracking rate (for dual-chamber (DDD) pacing) – Upper sensor rate (for rate modulation)

– AV delay • Demand mode. Refers to pacing without regard to the underlying rhythm. It is not available in an ICD unless shock therapy is disabled. Examples include: – AOO: Asynchronous atrial only pacing – VOO: Asynchronous ventricular only pacing – DOO: Asynchronous AV sequential pacing • Rate modulation. Describes the ability to detect exercise and increase the pacing rate (present in all new devices). Various sensors include both mechanical and electronic elements. Knowledge of sensor type and settings can prevent inappropriate treatment and patient injury when iatrogenic sensor stimulation from skin preparation or electrical interference might increase the paced heart rate in the perioperative period (9). • AV sequential pacing (DDD mode, also called p-wave synchronous ventricular pacing) represents the most common pacing mode in the US. It preserves AV synchrony, avoiding atrial contraction against a closed AV valve, which can create vertigo or pulsating symptoms called pacemaker syndrome. • Battery depletion can result in pacing system failure and failure to deliver high voltage therapy for an ICD. Low battery voltage also puts the device at-risk for EMI-induced reset. Pacing mode changes are designed to limit batter current drain; some CIEDs convert from dual chamber to single chamber pacing when elective replacement battery voltage is detected. • Outright lead detachment is rare after the first 6 weeks of implant. However, lead tip fibrosis resulting in sensing or pacing threshold issues and lead fracture or insulation failure remain important long-term issues.

PREVENTATIVE MEASURES

• Reprogramming to an asynchronous mode can prevent inappropriate pacing inhibition from EMI. For PPM (but not for ICD), most generators will respond to the placement of a magnet by converting to asynchronous pacing at a manufacturer-specific rate that identifies battery performance. Placing a magnet over an ICD usually suspends or disables anti-tachycardia detection or therapy, but rarely alters pacing (only ICDs from Sorin Corporation change pacing rate, but not mode, when exposed to a properly placed magnet). ICD patients requiring asynchronous pacing will therefore always require formal device reprogramming. Note that many CIEDs can have their magnet switch programmed off. • Minimizing intraoperative EMI: – Bipolar electrocautery should be used if possible – Short, intermittent bursts of electrocautery should be used at the lowest possible energy • The electrosurgery current-return (“grounding”) pad should be positioned so that the electrosurgery current path does not cross the chest or pacer system (6)[C].

PREOPERATIVE ASSESSMENT • Testing for PD is performed by the cardiology/pacemaker team during each regular device follow up. Various testing protocols exist that establish the presence of an inadequate or absent intrinsic rhythm at a low pacing rate. Testing is done by temporarily programming a low ventricular base rate (30–40 bpm) and assessing for the presence or absence of an

underlying rhythm and/or the onset of associated symptoms. • According to the Heart Rhythm Society (HRS)/American Society of Anesthesiologists (ASA) Consensus statement (10), CIED clinic records should be obtained for every patient prior to any elective case to reduce or eliminate confusion regarding CIED function, and the patient’s CIED physician should be contacted. In the absence of records, the HRS/ASA statement suggests a preoperative interrogation to ensure appropriate device function and programming with respect to the upcoming procedure. Some parameters (such as a reduced pacing rate for nighttime or a long AV delay) might need to be changed for an operative procedure, especially if large blood loss or fluid shifts are expected. In general, patient reports should not be trusted; many report a pacemaker check after only a simple 12 lead electrocardiographic evaluation and patients rarely understand or are informed about CIED or lead alerts.

TREATMENT Temporary pacing modalities in the perioperative period may be used to stabilize a patient with urgent or emergent pacing indications: transesophageal, transcutaneous, and transvenous pacing. Esophageal pacing (EP) utilizes a specially constructed esophageal stethoscope with two stainless steel rings, designed to stimulate the left atrium. EP requires intact atrial and AV nodal function; thus it is absolutely contraindicated in the presence of AF or flutter, as well as significant AV nodal disease. Transcutaneous pacing utilizes 2 cutaneous pads with pacing achieved via an external defibrillator. Transvenous pacing is achieved by placing a temporary pacing wire through a central vein so that its tip lies in the right ventricle. It is more reliable and can therefore be used for a longer duration than EP or transcutaneous pacing.

FOLLOW-UP • PPM patients should have a comprehensive device interrogation at least annually. ICD patients should undergo a comprehensive device interrogation every 3–6 months, and CRT patients should be checked every 3 months. For some low risk, non PD patients with the latest generators, telephone interrogations can replace office visits. • Postoperatively, care must be taken to ensure that a CIED continues to function appropriately. CIEDs exposed to EMI, especially if pacing inhibition was observed or blood transfused, should be checked. The HRS/ASA states that for any high-risk patient, or where preoperative or intraoperative programming was performed, or where a question arose about pacing or ICD function, that a postoperative check should be performed prior to discharge from a monitored environment. For a low-risk patient, a CIED could be checked in an ambulatory clinic after patient discharge from the PACU. The site of the postoperative check should be established during the preoperative process, since the patient’s CIED physician should be involved in the perioperative planning.

CLOSED CLAIMS DATA

Analyses of pacing systems show failures at multiple levels. The 1990–2002 FDA Data

Analysis (11) showed that there were 2.25 million PPMs and 415,780 ICDs implanted in US. The annual malfunction replacement rate for PPMs was 4.6 per 1,000 implants and 20.7 per 1,000 implants for ICDs. 61 deaths were attributed to generator malfunction. Mechanical problems with device leads were common; the reported failure rate of ICD leads at 8 years was 28–40% (1).

REFERENCES

1. orantzopoulos P, Letsas P, Grekas G, et al. Pacemaker dependency after implantation of electrophysiological devices. Europace. 2009;11:1151–1155.

2. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352:225–237.

3. Uslan DZ, Tleyjeh IM, Baddour LM, et al. Temporal trends in permanent pacemaker implantation: A population-based study. Am Heart J. 2008;155: 896–903. 4. Nagatomo T, Abe H, Kikuchi K, et al. New onset of pacemaker dependency after permanent pacemaker implantation. Pacing Clin Electrophysiol. 2004;27:475–479. 5. Lelakowski J, Majewski J, Bednarek J, et al. Pacemaker dependency after pacemaker implantation. Cardiol J. 2007;14:83–86. 6. American Society of Anesthesiologists. Practice advisory for the perioperative management of patients with cardiac implantable electronic devices: Pacemakers and implantable cardioverter-defibrillators: An updated report by the American society of anesthesiologists task force on perioperative management of patients with cardiac implantable electronic devices. Anesthesiology. 2011;114:247–261. 7. Tang AS, Roberts RS, Kerr C, et al. Relationship between pacemaker dependency and the effect of pacing mode on cardiovascular outcomes. Circulation. 2001;103:3081–3085. 8. Bernstein AD, Daubert JC, Fletcher RD, et al. The revised NASPE/BPEG generic code for antibradycardia, adaptive-rate, and multisite pacing. North American Society of Pacing and Electrophysiology/British Pacing and Electrophysiology Group. Pacing Clin Electrophysiol. 2002;25:260–264. 9. Lau W, Corcoran SJ, Mond HG. Pacemaker tachycardia in a minute ventilation rateadaptive pacemaker induced by electrocardiographic monitoring. Pacing Clin Electrophysiol. 2006;29:438–440. 10. Crossley GH, Poole JE, Rozner MA, et al. The Heart Rhythm Society (HRS)/American Society of Anesthesiologists (ASA) Expert Consensus Statement on the Perioperative Management of Patients with Implantable Defibrillators, Pacemakers and Arrhythmia Monitors: Facilities and Patient Management This document was developed as a joint project with the American Society of Anesthesiologists (ASA), and in collaboration with the American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Heart Rhythm. 2011;8:1114–1154. 11. Maisel WH, Moynahan M, Zuckerman BD, et al. Pacemaker and ICD generator malfunctions: analysis of Food and Drug Administration annual reports. JAMA. 2006;295:1901–1906.

12. Maisel WH, Hauser RG, Hammill SC, et al. Recommendations from the Heart Rhythm Society Task Force on Lead Performance Policies and Guidelines Developed in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA). Heart Rhythm. 2009;6:869–885.

ADDITIONAL READING

• Moses HW, Mullin JC. A Practical Guide To Cardiac Pacing. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007.

See Also (Topic, Algorithm, Electronic Media Element) • Cardiac Pacemaker Cells • Bradycardia • Hypertrophic Cardiomyopathy

CODES ICD9 • V45.01 Cardiac pacemaker in situ • V45.02 Automatic implantable cardiac defibrillator in situ ICD10 • Z95.0 Presence of cardiac pacemaker • Z95.810 Presence of automatic (implantable) cardiac defibrillator

CLINICAL PEARLS

• PD patients are at high risk for serious injury or death in the event of pacing system malfunction. • Perioperative pacing system malfunction from EMI and other factors is difficult to predict and occurs commonly. • A key preoperative consideration is establishing the presence or absence of PD in PPM patients if EMI is likely to be present. When EMI is likely (such as intraoperative monopolar electrosurgery), PD patients might require reprogramming to an asynchronous pacing mode or application of temporary pacing modalities.

PANCREATIC TRANSPLANTATION Selma Ishag, MB, BS, MD Catherine Ifune, MD, PhD

BASICS DESCRIPTION General

• Transplantation of the pancreas is the surgical treatment for insulin dependent diabetes mellitus. It can be performed – Simultaneously with a kidney transplant (Simultaneous Pancreas-Kidney, SPK); most commonly performed. Indicated in diabetic patients with imminent or established endstage renal disease (ESRD). – Following a kidney transplant (Pancreas After Kidney, PAK). May be indicated in diabetic patients who have received a renal transplant. – Alone (Pancreas Transplant Alone, PTA); rarely performed. Indicated for severe metabolic complications of diabetes, intolerance to exogenous insulin therapy, and failure of insulin therapy to prevent acute complications. • Preparation of the graft includes removing the recipient’s spleen and mobilizing the portal vein. This is followed by reconstructing the donor’s superior mesenteric and splenic arteries to form a Y graft using the donor iliac artery bifurcation. • Arterial anastomosis is to the recipient’s iliac artery and the venous anastomosis is either to the recipient’s iliac vein (systemic drainage, technically easier) or portal vein (portal drainage, more physiologic since insulin undergoes first pass metabolism in the liver, avoiding hyperinsulinemia). • Drainage of exocrine secretion is by anastomosing the donor’s duodenal segment to either the recipient’s bladder (bladder drainage, BD) or small bowel (enteric drainage, ED). BD is used more frequently in PTA to monitor urine amylase levels as an indicator for rejection. ED is used more frequently for SPK. • Exclusion criteria include: – Insufficient cardiac reserve – Age >65 years – Obesity (>50% ideal body weight) – Malignancy – Active infection – Ongoing drug or alcohol abuse – History of non-compliance – Psychological instability • An evolving, less invasive treatment for insulin dependent diabetes mellitus is percutaneous islet cell transplantation into the portal vein; however, the risk of immunosuppression may not justify the current outcome benefit. On the other hand, autografts of islet cells after

pancreatic resection for pancreatitis maintains normoglycemia for several years; additionally, no immunosuppression is necessary.

Position

• Supine, with arms abducted <90° • Protect dialysis access site

Incision

• Transperitoneal midline incision • Sometimes 2 separate lower quadrant incisions for SPK

Approximate Time

3–8 hours if combined transplant EBL Expected 250–500 mL

Hospital Stay

Intensive care unit for 24–48 hours Special Equipment for Surgery

Major abdominal surgery equipment EPIDEMIOLOGY Incidence

1,500–1,800 per year worldwide Prevalence

30,000 pancreatic transplants performed worldwide from 1966–2008 Morbidity

• Immediate surgical complications 13% • Graft rejection 5–25%, peaks between 3 and 12 months post-transplant

Mortality

Patient survival of >90% at 3 years and 67% at 10 years. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintain adequate graft perfusion by optimizing volume status and perfusion pressure. • Maintain euglycemia

PREOPERATIVE ASSESSMENT SYMPTOMS

• Hyperglycemia: Polyuria, polydipsia, weight loss, nausea, vomiting, and abdominal pain if

ketoacidotic • Hypoglycemia: Sweating, anxiety, tremor, CNS symptoms including seizures or loss of consciousness • In chronic diabetics, symptoms of end-organ involvement need to be assessed

History

• Diabetes mellitus, mostly Type I; Type II in 6–7% • Rarely, total pancreatectomy • Renal failure; assess hemodialysis duration, schedule, complications (hyperkalemia, hypotension)

Signs/Physical Exam

• Airway exam • Assessment of volume status and of veins for peripheral IV placement. • Assessment of AV fistula or dialysis access site.

MEDICATIONS

• Insulin • Treatment for end-organ impairment

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC • Basic metabolic panel • Type and cross match blood • Screening for ischemic heart disease: EKG, stress test, coronary angiography, if necessary.

CONCOMITANT ORGAN DYSFUNCTION • Macrovascular complications of diabetes – Coronary artery disease – Peripheral vascular disease – Stroke • Microvascular complications of diabetes – Diabetic nephropathy – Neuropathy – Retinopathy • Autonomic neuropathy, gastroparesis • Anemia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolysis as needed

• Consider aspiration prophylaxis • Continue cardioprotective medications

Special Concerns for Informed Consent • Blood transfusion • Invasive monitoring lines • Postoperative ventilatory support

Antibiotics/Common Organisms

• Second generation cephalosporin. Repeat dosing may be necessary. • Antifungal usually started postoperatively

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia • Postoperative systemic heparinization contraindicates epidural catheter placement for postoperative pain management.

Monitors

• Standard ASA monitors • Arterial line prior to induction if significant cardiac disease or autonomic dysfunction (avoid site of AV fistula) • One large bore peripheral IV • Central venous catheter placement for volume status monitoring, infusion of antithymocyte globulin, possible vasoactive infusion and postoperative hyperalimentation. • Foley catheter • Nasogastric tube • Mechanical DVT prophylaxis

Induction/Airway Management

• GERD and gastroparesis are common. Consider a RSI. IV access is generally preferred in older children/adolescent patients meeting “full stomach” criteria. • Potential for difficult airway due to glycosylation of joints (stiff-joint syndrome) affecting temporomandibular and atlanto-occipital joints.

Maintenance

• Balanced technique with muscle relaxation. • Avoid nitrous oxide. Consider the use of atracurium or cisatracurium for muscle relaxation. Use narcotics with limited active metabolites such as hydromorphone. • Start immunosuppressive therapy after induction of anesthesia. Most transplant centers use induction therapy with a single high dose of corticosteroids followed by alemtuzumab or an infusion of antithymocyte globulin intraoperatively. Of note, the antithymocyte globulin can cause hypotension and in some cases the infusion rate must be reduced to maintain adequate BP. • Hemodynamics

– Maintain an elevated central venous pressure (CVP) (12–14 mm Hg) and systolic BP (around 140 mm Hg) with fluid administration, and inotropes if necessary. – Goal is optimal perfusion of the transplanted organs. This is balanced by the need to avoid graft and bowel edema which can complicate the pancreas transplant as well as abdominal closure at the end of the case. – Expect hypotension and acidosis at reperfusion and prepare to promptly optimize hemodynamics, to maintain graft blood flow. • Correct acid-base status and normalize electrolytes • Consider mannitol for free radical scavenging before reperfusion. • Glycemic control – Check blood glucose every hour initially and every half-hour post reperfusion. – An insulin infusion may be used to keep blood sugars between 100 and 200 mg/dL. Tight glycemic control enhances graft survival by decreasing metabolic demand on islet cells until reperfusion injury has resolved. – Octreotide is a somatostatin analogue which reduces gastrointestinal, biliary, and pancreatic secretions and may also be used to transiently rest islet cells. – Continuous D5W infusion to provide intracellular nutrition and decrease free fatty acid production avoiding the potential for adverse cardiac events. • Maintain normothermia.

Extubation/Emergence

• Fully awake, following standard criteria • Avoid hypertension

POSTOPERATIVE CARE BED ACUITY

• Surgical intensive care unit. Careful monitoring of volume status, hemodynamics, electrolytes and glucose. • Monitor for bicarbonate loss in BD. • Immunosuppression: Maintenance therapy is started postoperatively with a calcineurin inhibitor (usually tacrolimus), mycophenolate mofetil, and corticosteroids. Studies have shown that this triad provides excellent graft survival of 86% at 1 year and 53% at 10 years.

ANALGESIA

Moderate pain is consistent with abdominal surgery. Usually IV opioid PCA is used. COMPLICATIONS

• Assess for postoperative cardiac dysfunction • Surgical – Technical failure due to decreased vascularity of the pancreas – Thrombosis requires graft removal; seen in 6% of cases. Routine postoperative antithrombotic prophylaxis may decrease the incidence. – Infection 2–3% – Pancreatitis 2–3%. Early presentation is possibly from ischemia reperfusion injury;

whereas late presentation can be from urinary reflux into the graft if BD. Treatment consists of supportive measures. – Bleeding <1% • Acute rejection can occur after 7 days. Heavy immunosuppression is necessary.

PROGNOSIS

• Improved life expectancy. At 5 years, diabetics on dialysis have a survival of 30–40% versus 78% after kidney transplant and 82% after SPK. • Improved quality of life • Improved renal graft function • Regression of atherosclerosis with reduced rates of MI and acute pulmonary edema • Arrested deterioration of retinopathy • Rejection occurs for both organs simultaneously and is monitored by creatinine levels

REFERENCES

1. Larson-Wadd K, Belani KG. Pancreas and islet cell transplantation. Anesthesiology Clinics of North America. 2004;22:663–674. 2. Koehntop DE, Beebe DS, Belani KG. Perioperative anesthetic management of the kidneypancreas transplant recipient. Current opinion in Anesthesiology. 2000;13:341–347. 3. Gruessner AC, Sutherland DER, Gruessner RWG. Pancreas transplantation in the United States: A review. Current Opinion in Organ Transplantation. 2010;15:93–101. 4. American Diabetes Association. Pancreas and Islet Transplantation in Type I Diabetes. Diabetes Care. 2006;29(4):935. 5. White SA, Shaw JA, Sutherland DER. Pancreas transplantation. Lancet. 2009;373:1808– 1817.

ADDITIONAL READING

• Beebe DS, Kendall DM, Gruessner RWG, et al. Pancreas transplantation. In: Anesthesia and transplantation. Sharpe MD, Gelb AW, eds. Boston: Butterworth-Heinmann; 1999:217–240. • Heilman RL, Mazur MJ, Reddy KS. Immunosup-pression in simultaneous pancreas-kidney transplantation. Drugs. 2010;70(7):793–804. See Also (Topic, Algorithm, Electronic Media Element)

• Renal Transplantation • Diabetes Mellitus • Hyperglycemia

CLINICAL PEARLS

• Check immunosuppression regimen and start immunosuppressive therapy soon after induction of anesthesia. • Prepare for tight blood glucose control intraoperatively. • Careful fluid and hemodynamic management to optimize perfusion of the transplanted

organs • Anticipate and treat hemodynamic changes at reperfusion

PAO2 Matthew Ellison, MD Erik Olness, MD

BASICS DESCRIPTION

• PaO2 is the partial pressure of oxygen in the arterial blood. Although PaO2 is in equilibrium

with dissolved (blood) and bound (oxyhemoglobin) oxygen, these other states do not exert partial pressure. • Although normal values can be estimated by the use of a simple equation, accurate values must be determined by laboratory arterial blood gas (ABG) analysis. • Hypoxemia is defined as decreased PaO2 in blood whereas hypoxia is defined as low oxygen availability to the body or to individual organs/tissues • PAO2 is the alveolar partial pressure of oxygen. In contrast to PaO2, it is a calculated value. PHYSIOLOGY PRINCIPLES

• The partial pressure of a gas is defined as the pressure exerted independently by that gas in a mixture of gases – According to Dalton’s Law, the total pressure of a mixture of gases is equal to the sum of the partial pressures of each individual gas • The partial pressure of a gas dissolved in a liquid is the partial pressure that would be exerted by the gas while in a gaseous phase and while in equilibrium with the liquid – According to Henry’s Law, if one were to double the pressure of a gas, then the concentration of that gas in solution would be doubled as well • Solubility is the ability of a substance (O2) to dissolve in a solute (blood). The solubility coefficient of a gas is the volume of the gas that can be dissolved in a certain volume of solvent at a specified temperature and pressure – At standard body temperature, the solubility coefficient (and the solubility) of CO2 is approximately >20 times that of O2; therefore, diffusion abnormalities should not result

in hypercapnia • The net diffusion of a gas, such as O2, is dependent on the:

– Partial pressure gradient. Since the partial pressure of O2 in the alveoli (PAO2) is greater than the partial pressure of the dissolved O2 in the blood, more O2 molecules will diffuse from the alveoli into the pulmonary capillary blood. It is also dependent on Diffusion coefficient. Based on the solubility and molecular weight of the gas in question Thickness and surface area of the pulmonary capillary membrane. Because of its tremendous size and microscopic thickness (0.4–0.5 μm), a normal pulmonary capillary membrane provides almost no resistance to the diffusion of lipid soluble gases such as

O2 and CO2

Transit time. The rate limiting step in the transport of O2 from the alveoli to the blood is

typically the loading of O2 onto Hb, not the diffusion of O2 across the pulmonary

capillary membrane • Diffusion capacity is the amount of gas (O2) that can be transferred from the alveoli to the blood across the alveolar-capillary membrane. The O2 diffusing capacity at rest in an adult

male is ∼21 mL/min/mm Hg and may increase to 65 mL/min/mm Hg with strenuous exercise • PaO2 will be
venous blood called the venous admixture. Normally, the venous admixture consists of blood from the bronchial-pulmonary venous communication, the Thebesian circulation, and low V/Q areas in the lung

ANATOMY

• Hemoglobin is a molecule consisting of 4 heme and 4 protein subunits. Heme is an ironporphyrin compound comprising an essential part of O2 binding sites; only the divalent (+2 charge) form of iron can bind O2. Hemoglobin A1 (normal adult hemoglobin) consists of 2α and 2β chains held together by weak bonds between the amino acid residues. Theoretically, each gram of Hb can carry up to 1.39 mL of O2.

• Peripheral chemoreceptors include the aortic and carotid bodies; PaO2 has a minimal effect

on central chemoreceptors – The aortic bodies (found in the aortic arch and its branches) have predominantly circulatory effects, while the carotid bodies (located at the bifurcation of the common carotid artery) have predominantly ventilatory effects – Neural output from the aortic bodies travels to the medullary centers via the vagus (CN X) nerve, while output from the carotid bodies reaches the central respiratory centers via the afferent glossopharyngeal (CN IX) nerve – Both carotid and aortic bodies are stimulated by decreased PaO2, but not by decreased SaO2 or CaO2

– Neural activity from these receptors begins to increase when the PaO2 falls to <100 mm

Hg. When PaO2 levels reach 60–65 mm Hg, neural activity is substantially augmented to

increase the minute ventilation – Patients that depend on hypoxic ventilatory drive (those with COPD, for example) have PaO2 values in the mid 60s; this must be considered when weaning these patients from mechanical ventilatory support as spontaneous ventilation will not resume until the PaO2 falls to <65 mm Hg

DISEASE/PATHOPHYSIOLOGY

• The oxygen–hemoglobin (also known as the oxyhemoglobin) dissociation curve is the graphical illustration of the measured relationship between PaO2 and SaO2.

– SaO2 is a measure of the percentage of hemoglobin binding sites occupied by O2. A normal PaO2 of 100 mm Hg results in a SaO2 of about 98%

– The curve is sigmoidal in shape; it represents conformational changes to Hb as more O2

molecules bind to, or dissociate from, it. These changes accelerate the loading, or unloading, of the fourth O2 molecule.

– The “S” shape also minimizes the effects of changes in PaO2 on the SaO2, while in the normal range. However, there is a “steep” vertical section where small changes in PaO2

result in significant drops in the SaO2; it also corresponds to the PaO2 level where

chemoreceptors begin firing. – P50 (the point at which Hb is 50% saturated) normally falls at a PaO2 of 26.7 mm Hg.

– If the oxyhemoglobin curve is shifted to the left (reduced P50), then hemoglobin has a

higher than normal affinity for O2, resulting in decreased O2 unloading. Circumstances

causing a leftward shift include: Abnormal hemoglobin (fetal), alkalosis, carboxyhemoglobin, decreased 2,3-DPG, hypothermia, and methemoglobin. When the curve is shifted to the right (increased P50), Hb has a lower affinity for O2 leading to increased O2 unloading in the periphery. Shifting of the curve to the right may be caused by: Abnormal hemoglobin, acidosis, hyperthermia, increased 2,3-DPG, and increased CO2

• The most common mechanism for hypoxemia is an increased alveolar-arterial gradient • The diffusion of O2 can be slowed when the thickness of the pulmonary capillary membrane

becomes pathologically thickened. This may occur in diseases such as pulmonary fibrosis, pulmonary edema (accumulation of interstitial fluid in the membrane), and pneumonia (inflammatory fluid accumulation in the membrane)

PERIOPERATIVE RELEVANCE

• Dissolved oxygen usually has very little impact on the total arterial oxygen content because most of the oxygen in blood is carried by hemoglobin (see equation ) • Pulse oximetry is listed an American Society of Anesthesiologists Standards for Basic Anesthetic Monitoring. It is a safe, noninvasive, continuous method to measure oxygenation and rapidly detect hypoxia. Oximetry readings provide an estimation of the PaO2, based on

the oxygen–hemoglobin curve. – Values are based on the Lambert–Beer law stating that oxyhemoglobin and deoxyhemoglobin absorb different quantities of red and infrared light – Oxyhemoglobin (HbO2) absorbs more infrared light at a wavelength of 940 nm and therefore, appears red to the human eye – Deoxyhemoglobin (Hb) absorbs more red light at 660 nm, appearing blue or cyanotic – Oxygen saturation is calculated by a microprocessor that compares the ratio of light absorption at the red and infrared wavelengths – Functional oximetry is defined as HbO2 divided by the sum of HbO2 and Hb; it does not

include COHb and MetHb which, in normal physiological states, are present in small concentrations. The operating room and ICU pulse oximeter are functional pulse

oximeters. – Fractional oximetry is defined as the ratio of HbO2 to the total Hb (all 4 species: HbO2,

Hb, COHb, MetHb). It is measured by laboratory co-oximeters. – The pulse oximeter isolates the pulsatile component of blood based on plethysmography, in an attempt to eliminate false readings from venous blood or tissue – Pulse oximeters also measure heart rate based on this pulsatile flow in addition to the SpO2

• Although generally very accurate at SpO2 readings from 70 to 100%, pulse oximeters have

several potential problems – Values reflect an average value over a time span of 5–8 seconds; this delay can translate into a delay in treatment. – Artifacts may be caused by fingernail polish, ambient light, methylene blue dye, and motion. – Low perfusion states such as cardiac arrest, hypothermia, increased SVR, severe anemia, cardiac bypass, or tourniquet placement may affect the ability to obtain a reading – Carboxyhemoglobin (COHb) absorbs light in a similar manner to HbO2, resulting in a

falsely high reading in patients with CO poisoning – Methemoglobin absorbs light equally at red and infrared wavelengths, providing a constant pulse oximeter reading of ∼85%. SpO2 may be falsely high or low depending on the actual SaO2

– Unable to distinguish between PaO2 values greater than 100 mmHg – will all have oxygen

saturations of 100% • ABG analysis measures PaO2 values as well as arterial pH, PaCO2, HCO3−, and base deficit. It allows for an assessment of oxygenation (PaO2), ventilation based on the PaCO2, and

provides insight into the acid–base status with pH measurement and base deficit. • Normal range of PaO2 in an adult is 60–100 mm Hg and is dependent on multiple factors

including alveolar ventilation, FiO2 (inspired O2 concentration), SvO2 (mixed venous O2 saturation), and ventilation–perfusion ratio – If PaO2 is <60 mm Hg, then hypoxemia is present

– If hypoxemia is present, calculation of the A-a gradient will help to determine the cause – Normal A-a gradient may result from hypoventilation or low FiO2

– Increased A-a gradient can be caused by V/Q mismatching, increased right to left shunting, and diffusion abnormalities

EQUATIONS

• Approximation of arterial oxygen tension based on age = PaO2 = 102 – Age/3

• Alveolar gas equation = PAO2 = FiO2 (PB – PH2O) – PACO2 / R; PACO2/R is used an as indirect measure of VO2/VA where VO2 is O2 consumption and VA is alveolar ventilation

• Arterial Oxygen Content = CaO2 = O2 bound to Hb + O2 dissolved in blood = [SaO2 × (Hb ×

1.34)] + [PaO2 × 0.0031]

• Oxygen Delivery = DO2 = CO × CaO2

• Dalton’s Law = Ptotal = Pgas1 + Pgas2 + PgasN

• Henry’s Law = Cg = k × Pg, where Cg is concentration of the gas in solution, k is a solubility constant, and Pg is the partial pressure of the gas

• Diffusion Capacity for O2 = DLO2 = Oxygen Uptake / (PAO2 – PC’O2) • Functional Oximetry = SpO2 = HbO2 / (HbO2 + Hb)

• Fractional Oximetry = SaO2 = HbO2 / (HbO2 + Hb + COHb + MetHb + other hemoglobins)

REFERENCES

1. Boemke W, Krebs MO, Rossaint R. Blood gas analysis. Anaesthesia. 2004;53(5):471–492. 2. ilber HC, Vender JS. Arterial blood gas monitoring. Crit Care Clin. 1995;11(1):233–248. 3. Story DA. Alveolar oxygen partial pressure, alveolar carbon dioxide partial pressure and the alveolar gas equation. Anesthesiology. 1996;84(4):1011.

ADDITIONAL READING

• Sherwood, Lauralee. Human Physiology: From Cells to Systems. 3rd ed. Belmont: Wadsworth, 1997.

See Also (Topic, Algorithm, Electronic Media Element) • Mixed Venous Oxygen Saturation • Hemoglobin • Methemoglobinemia • Pulse Oximetry • Alveolar Arterial Gradient and Ratio

CLINICAL PEARLS

• PaO2 is a measured value obtained from an ABG and PAO2 is a calculated value

• The A-a gradient for O2 is typically <15 mm Hg but increases up to 30 mm Hg as one ages

– Increased A-a gradient can be caused by V/Q mismatching, increased right to left shunting, and diffusion abnormalities • The majority of O2 transported in the blood is carried by Hb and not dissolved in the blood • The oxyhemoglobin dissociation curve is a sigmoidal shaped curve portraying the relationship between PaO2 and SaO2

– Causes of a leftward shift include: Abnormal hemoglobin (fetal), alkalosis, carboxyhemoglobin, decreased 2,3-DPG, hypothermia, and methemoglobin – Causes of a rightward shift: abnormal hemoglobin, acidosis, hyperthermia, increased 2,3DPG, and increased CO2

• PaO2 stimulates ventilation via the peripheral chemoreceptors with minimal effect on the

central receptors • Operating room pulse oximeters emit light at wavelengths or 660 and 940 nm and work based on Lambert–Beer law

PARATHYROIDECTOMY Joe C. Hong, MD

BASICS DESCRIPTION General

• Parathyroidectomy is indicated for the management of hyperparathyroidism. • The biochemical diagnosis of hyperparathyroidism is made in the setting of elevated serum calcium and parathyroid hormone (PTH) levels (1). • Causes of hyperparathyroidism include: – Primary: Direct hyper-functioning of the parathyroid gland due to parathyroid adenoma or glandular hyperplasia. – Secondary: Parathyroid hyperplasia caused by chronic renal disease or vitamin D deficiency. – Multiple endocrine neoplasia syndromes. – Parathyroid carcinoma. • When a single gland adenoma is suspected, localizing imaging studies (neck ultrasonography and 99mTc-Sestamibi scan) can aid with a limited and focused parathyroidectomy (2). • Multiple gland disease requires bilateral neck dissection and 4-gland bilateral exploration. Position

• Supine with arms tucked bilaterally. • A roll is placed transversely beneath the scapulae to facilitate mild neck extension, and thereby optimizes surgical exposure. • In patients with cervical spine disease, range of neck extension should be carefully assessed preoperatively.

Incision

• Focused parathyroidectomy: 2–3 cm transverse incision lateralized towards the side of the suspected adenoma. • Bilateral exploration or redo: 4–6 cm transverse midline neck incision.

Approximate Time

• Typically 30–60 minutes for focused parathyroidectomy. • Up to 2+ hours for bilateral exploration or redo parathyroidectomy.

EBL Expected

• Focused: Minimal • Bilateral exploration: 25–100 mL

Hospital Stay

• Depends on patient comorbidities. • Focused parathyroidectomy can be done on an ambulatory basis to 24-hour overnight stay. • Bilateral exploration or redo surgery usually requires a 24–48+ hour hospital course.

Special Equipment for Surgery

• Some surgeons prefer an electromyography (EMG) endotracheal tube for recurrent laryngeal nerve monitoring (3). • For deep neck dissections, an esophageal temperature probe may aid in the digital palpation of landmarks.

EPIDEMIOLOGY Incidence

• In the US: 100,000 cases of primary hyperparathyroidism per year • Single gland adenoma: ~80–85% • Multiple gland hyperplasia: ~10–15% • Double gland adenoma: ~2–5% • Parathyroid carcinoma: ~1%

Prevalence

• In the US population: 1:500–1:1,000 have a history of hyperparathyroidism. • Female > male (4:1) • Increases with age • Peak incidence in the 6th decade of life

Morbidity

• Recurrent laryngeal nerve injury: – Unilateral injury leads to hoarseness. – Bilateral partial injury can lead to complete airway obstruction or stridor and the need for intubation or tracheostomy. • Neck hematoma • Hypocalcemia • Operative failure to resect all sources of hypersecreting tissue (multiple gland hyperplasia or double adenoma).

Mortality

Extremely rare

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Severe symptomatic hypercalcemia with resulting intravascular volume depletion and cardiac dysrhythmia should be medically managed and optimized prior to surgery. • Preoperatively, consider IV hydration as this will restore intravascular volume and temporize hypercalcemia. • Furosemide, after volume resuscitation, will further decrease plasma calcium concentration prior to surgery. • Intraoperatively, the need for recurrent laryngeal nerve monitoring will preclude the use of

non-depolarizing muscle relaxants. • Dexamethasone is commonly used to temporize postoperative airway edema. • Bucking on emergence should be minimized to decrease the likelihood of neck hematoma formation.

PREOPERATIVE ASSESSMENT SYMPTOMS

• “Painful bones, renal stones, abdominal groans, and psychiatric moans.” • Often asymptomatic except for biochemical evidence of hypercalcemia and elevated PTH levels.

History

• Often asymptomatic; discovered after routine laboratory examination reveals hypercalcemia. • Non-specific history of bone pain, kidney stones, abdominal distress, anxiety, fatigue, and depression. • For secondary hyperparathyroidism, history of chronic renal insufficiency, end-stage renal disease. • Personal or family history of multiple endocrine neoplasia syndromes.

Signs/Physical Exam

• Skeletal “painful bones”: – Osteoporosis – Skeletal demineralization – Spontaneous fracture – Bone pain • Renal “kidney stones”: – Nephrolithiasis – Nephrocalcinosis – Reduced glomerular filtration – Polydipsia – Polyuria • Gastrointestinal “abdominal groans”: – Abdominal distress – Gastroduodenal ulcer – Gastroesophageal reflux disorder – Anorexia – Vomiting – Pancreatic calcification • Neuropsychiatric: “Psychiatric moans”: – Fatigue – Anxiety – Depression – Psychosis

– Somnolence – Coma • Cardiovascular: – Hypertension – Short QT interval – Intravascular volume depletion • Neuromuscular: – Muscle fatigue – Hypotonia

MEDICATIONS

• Bisphosphonates • Calcimimetics • Estrogen therapy in postmenopausal women

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Elevated serum calcium and PTH levels • Per routine labs based on comorbidity • EKG (short QT interval)

CONCOMITANT ORGAN DYSFUNCTION

• Renal insufficiency secondary to nephrolithiasis and nephrocalcinosis • Cardiac dysrhythmias and short QT interval secondary to hypercalcemia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Ensure adequate IV hydration as hyperparathyroid patients are often intravascularly volume depleted • Midazolam may be titrated to comfort, as anxiety is a prominent symptom of hypercalcemia. • Patients with bone pain may benefit from fentanyl premedication.

Special Concerns for Informed Consent

• Regional/local with sedation versus general anesthesia and the possibility of conversion from MAC to general anesthesia. • Possibility of postoperative intubation in rare cases of partial bilateral recurrent laryngeal nerve injury. Antibiotics/Common Organisms

First generation cephalosporins, such as cefazolin, is recommended prior to surgical skin incision. Clindamycin is an alternative for patients with a cephalosporin allergy.

INTRAOPERATIVE CARE Choice of Anesthesia

• For bilateral neck dissection, 4-gland exploration, and redo operations, a general endotracheal anesthesia is indicated. • MAC sedation +/− a superficial cervical plexus block or local infiltration is appropriate when well-localized single gland disease is expected (2). MAC should be avoided in obese patients or those with claustrophobia. • Even when general anesthesia is employed, a superficial cervical plexus block provides excellent postoperative analgesia.

Monitors

• Standard ASA monitors • Invasive monitoring is dictated by patient comorbidities.

Induction/Airway Management

• EMG endotracheal tube per surgeon request. • Induction and airway management is dictated by preoperative airway assessment. • Parathyroid pathology is rarely severe enough to cause compressive effects on the airway. However, review of available radiographic studies and discussion with the surgeon can delineate potential difficulties.

Maintenance

• Balanced technique is most commonly employed. • Since focused parathyroidectomies are short ambulatory procedures, the use of lowsolubility inhalational anesthetics such as desflurane or sevoflurane with or without nitrous oxide will result in rapid emergence. • Total intravenous anesthesia may be utilized to optimize EMG monitoring.

Extubation/Emergence

• Coughing/bucking on emergence should be minimized to decrease the likelihood of neck hematoma formation. Preintubation tracheal lidocaine can provide airway analgesia. • Communication with the surgeon regarding the likelihood of partial bilateral recurrent laryngeal nerve injury needs to take place prior to emergence and extubation. If present, the patient must remain intubated until a new tracheostomy is placed.

POSTOPERATIVE CARE BED ACUITY

• For uncomplicated procedures, a standard floor bed is usually adequate. • Patients for focused parathyroidectomy may be discharged on an ambulatory basis after adequate time of postoperative observation.

ANALGESIA

• Preoperative superficial cervical plexus block provides excellent postoperative analgesia. • Patients with bilateral neck dissection who are not blocked may be placed on patient-

controlled analgesia.

COMPLICATIONS

• Intraoperative complications include massive bleeding and possible stroke when injury to the nearby carotid artery occurs. • Intraoperative carotid sinus irritation may lead to hemodynamic fluctuations and bradyarrhythmia. • Respiratory compromise from an occult pneumothorax resulting from lower neck surgical dissection. • The SLN innervates the cricothyroid, a vocal cord (VC) tensor; whereas the RLN innervates the posterior cricoarytenoid (VC abductor) and the rest of the intrinsic laryngeal muscles (VC adductors). – Injury to the SLN: The cricothyroid muscle is unable to tense the VCs, giving a weak and husky voice. – Injury to RLN: Abductors are more vulnerable to injury. Therefore, partial nerve damage may result in a selective abductor paralysis while a complete transection paralyzes both adductors and abductors. Unilateral complete transection: Paralyzed VC that lies midway between adduction and abduction, just lateral to the midline (results in hoarseness). Unilateral partial transection: When abductors are more severely paralyzed than adductors, the affected VC lies in the midline adducted position. Bilateral complete transection: VCs are positioned midway between abduction and adduction. Breathing is still possible with a glottic opening smaller than normal. Bilateral partial transection: When abductor are more severely affected than adductors, both VCs meet in the midline and this results in complete airway obstruction. • Neck hematoma. • Hypocalcemia. • Hypoparathyroidism. • Failure to resect all hypersecreting parathyroid tissue resulting in persistent hypercalcemia.

PROGNOSIS

Surgical cure rate for primary hyperparathyroidism is above 95%.

REFERENCES

1. raser WD. Hyperparathyroidism. Lancet. 2009; 374(9684):145–158. 2. Shindo ML, Rosenthal JM, Lee T. Minimally invasive parathyroidectomy using local anesthesia with intravenous sedation and targeted approaches. Otolaryngol Head Neck Surg. 2008;138(3):381–387. 3. Miller MC, Spiegel JR. Identification and monitoring of the recurrent laryngeal nerve during thyroidectomy. Surg Oncol Clin N Am. 2008; 17(1):121–144.

ADDITIONAL READING

• Adler JT, Sippel RS, Chen H. New trends in parathyroid surgery. Curr Probl Surg. 2010;47(12):958–1017.

• Felger EA, Kandil E. Primary hyperparathyroidism. Otolaryngol Clin North Am. 2010;43(2):417–432. See Also (Topic, Algorithm, Electronic Media Element)

• Thyroidectomy • Hypocalcemia • Recurrent Laryngeal Nerve • Carotid Sinus • Deep Extubation • Vocal cord palsy

CLINICAL PEARLS

• Severe symptomatic hypercalcemia from hyperparathyroidism is a medical emergency. Management consists of IV hydration and furosemide prior to surgical resection. • Intraoperatively, the need for recurrent laryngeal nerve monitoring will preclude the use of non-depolarizing muscle relaxants. • Superficial cervical plexus block provides excellent analgesia for postoperative pain management. This regional technique can be the primary anesthetic in a focused parathyroidectomy. • Bucking on emergence should be minimized to decrease the likelihood of neck hematoma formation.

PARKINSON’S DISEASE

Christine E. Goepfert, MD, PhD, DESA

BASICS DESCRIPTION

• Parkinson’s disease is a common chronic, progressive, neurodegenerative disease with hallmarks of hypokinesia, rigidity, resting tremor, and postural instability. • Profound and selective loss of nigrostriatal dopaminergic neurons and the presence of alphasynuclein proteinaceous inclusions (Lewy bodies) EPIDEMIOLOGY Prevalence

• Overall: 13.4 per 100,000 persons • North America: ∼1 million people

Prevalence

• Increases with age: 1% in 60-year olds, 4–5% in those aged 85 years and above. • Race: Hispanics > non-Hispanic Whites > Asians > Blacks • Gender: Men slightly > women

Morbidity

See concomitant organ dysfunction Mortality

• Comparable to the general population, although may be increased with male gender, gait disorder, and absent rest tremor • Pneumonia is most often the terminal event

ETIOLOGY/RISK FACTORS

• Etiology is unknown, but believed to be multifactorial and likely a combination of polygenic inheritance, environmental exposure, and gene-environment interaction • Genetic factors (substantial): Multiple gene loci have been identified (Park1-17, SPG11, ACA2, 3). The majority are sporadic; family history comprises 20% of all cases • Environmental factors and neurotoxins: Pesticides (paraquat), herbicides, metals; chemical products (paints, glues, solvents, printing products, gasoline, asbestos, varnishes or stains); well water; living in rural areas within industrialized countries; farming (men only) • Idiopathic: Pathologic protein aggregation (alpha-synuclein, ubiquitinated proteins); oxidative stress; mitochondrial dysfunction; disturbed intracellular signal transmission; dysregulation of manganese homeostasis; neuroinflammation PHYSIOLOGY/PATHOPHYSIOLOGY

• Parkinson’s disease manifests from the degeneration of heterogeneous populations of neurons, most notably in the substantia nigra pars compacta (SNpc) and aminergic brainstem nuclei. This causes unopposed activity of GABA nuclei in the basal ganglia with resultant inhibition of thalamic nuclei and consequent suppression of the motor cortex. Clinical effects appear when there is 80% loss of striatal dopamine and 50% loss of nigral neurons. • Lewy bodies are concurrently found; they are intraneuronal cytoplasmic inclusions that are: Spherical, eosinophilic protein aggregates, and composed of numerous proteins (alphasynuclein, parkin, ubiquitin, synphilin, and neurofilaments). They are believed to interfere with normal cellular processes and sequester proteins important for cell survival (alternatively, it has been postulated that they are protective and sequester harmful protein aggregates).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients are at risk for postoperative pulmonary complications, primarily due to aspiration. Anesthetic management with appropriate dosing of drugs aims at a fully awake patient with positive protective reflexes at the time of emergence. • Cardiovascular instability may result from drug–drug interactions, malnutrition, and autonomic nervous system dysfunction • Patients may be more prone to hypothermia secondary to malnutrition and autonomic nervous system dysfunction.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Motor symptoms: Bradykinesis, hypokinesis, rigidity, tremors, postural instability, dysphagia • Dystonias from L-dopa • Confusion, dementia

History

‘Shaking palsy’, first described in 1817 by Dr. James Parkinson (London) Signs/Physical Exam

Reduced mouth opening from rigidity TREATMENT HISTORY

• Surgery: Gpi-pallidotomy, VL-thalamotomy • Deep brain stimulation – VIM (tremor) – STN and GPI (rigidity, dyskinesia) • Experimental therapies: Stem-cell therapy, fetal tissue transplantation, adrenal medullary transplants

MEDICATIONS

• Goals: Increase dopamine in basal ganglia (not periphery), decrease side effects of

acetylcholine on neurons • Levodopa (with peripheral inhibitor of dopa decarboxylase carbidopa or benserazide): Most effective medication to improve motor symptoms; however has a short half-life. Side effects: Motor fluctuations, peak dose dyskinesia and freezing, and acute dopaminergic side effects (nausea, vomiting, orthostatic hypotension, hallucinations, psychosis) • COMT inhibitors (entacapone, tolcapone): Extends half-life of levodopa by preventing its metabolism. Side-effect: Hepatic failure • Dopamine agonists. Ergots and non-ergots directly stimulate receptors in the striatum. Ergotrelated side effects: Pulmonary fibrosis, cardiac valve fibrosis, erythromelalgia, and dopaminergic side effects (nausea, vomiting, orthostatic hypotension, hallucinations, impulse control disorders, sleep attacks, leg edema) • Anticholinergic drugs. Most effective on tremor; however, use is limited by cognitive side effects such as confusion and hallucinations, urinary retention, tachycardia, dry mouth, and eyes • NMDA antagonists (amantadine). Releases dopamine from central neurons and delays uptake; also an anticholinergic. Side effects: Hallucinations, confusion, leg edema, urinary retention • MAO-B inhibitors (selegiline, rasagiline, deprenyl). Increase dopamine through blockade of MAO-B oxidation of dopamine. Side effects: Serotonergic syndrome, dietary restrictions

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, serum albumin/transferrin: Might be deranged through malnutrition • Blood glucose: If taking selegiline • Hepatic enzymes: If taking tolcapone • ECG: For assessment of arrhythmias, and if taking amantadine (long QT) • CXR, PFTs, possibly ABG: If respiratory dysfunction present

CONCOMITANT ORGAN DYSFUNCTION

• Neuropsychiatric symptoms: Olfactory deficits (70–100%); fatigue (40–70%); depression (25–50%); psychosis (16–40%), mostly visual and increased with dopaminergic medications; dementia (25–35%); apathy; impulsive and compulsive behavior (sexual disinhibition); cognitive dysfunction; sleep disturbances; restless legs. • Pain (40–70%) secondary to dystonia and myogelosis • Ophthalmologic disturbances: Decreased lash reflexes, dry eyes, saccadic eye movements • Motor: – Bradykinesia/hypokinesia: Dysarthria, dysphagia, reduced movements, small steps, propulsion and retropulsion, micrographia, hypomimia, freezing – Rigidity: Neck, jaw, contractures – Tremors: At rest (distally), postural – Postural instability: Falls, decreased movement in large joints, loss of balance • Airway and respiratory systems: Diminished cough reflex; abnormal control and function of intrinsic laryngeal and pharyngeal muscles due to rigidity; bradykinesia; decreased coordination; and an obstructive ventilatory pattern in up to 1/3rd of patients.

• Autonomic nervous system: Postural instability, urinary incontinence, gastroparesis, defective cardiovascular control, impaired temperature regulation, disturbance of sweating • Cardiovascular system: Arrhythmias, leg edema, orthostatic, or drug-induced hypotension • Gastrointestinal function: Dysphagia, hypersalivation (70–80%), due to reduced automatic swallowing; weight loss; and malnutrition

CIRCUMSTANCES TO DELAY/CONDITIONS

Insufficient medical therapy with prolonged off-phases may hamper extubation CLASSIFICATIONS

• Hoehn and Yahr staging of PD from 1 to 5 • Unified Parkinson Disease Rating Scale (UPDRS): – Mentation, behavior, mood – Activities of daily living – Motor symptoms

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines: Increased sensitivity, prolonged effects • Continue Parkinson’s medications as close to time of surgery (except in DBS procedures) • Beta-blockers: Suppress tremor • Anticholinergics: Diphenhydramine can decrease tremors and provide sedation.

Special Concerns for Informed Consent

Dementia in up to 35%; may need to acquire consent from family or power of attorney. INTRAOPERATIVE CARE Choice of Anesthesia

• Regional anesthesia: Should be considered when feasible as it has the benefit of avoiding airway instrumentation. Neuraxial techniques, however, can cause hypotension due to sympatholysis • General anesthesia: Hemodynamic instability may occur secondary to hypovolemia, norepinephrine-depletion, autonomic dysfunction, malnutrition, and drug-induced hypotension Monitors

• Standard ASA monitors • Foley catheter if urinary incontinence • Invasive monitors may be indicated depending on the severity of disease, comorbidities, and surgical procedure Induction/Airway Management

• Induction medications should be chosen and titrated carefully due to the risk of hypotension. Thiopentone and etomidate have been demonstrated to be clinically safe; propofol may cause dyskinesia and abolish tremors (avoid during DBS placement), however effects are unpredictable; ketamine may provoke an exaggerated sympathetic response, although in low-dose, it can be titrated to effect with good control of tremor and dysarthria. • Increased risk for arrhythmias during induction if electrolytes are deranged • Aspiration risk: Consider a rapid sequence (or modified) induction if gastroparesis, hypersalivation, dysphagia are present. Avoid succinylcholine due to the potential for hyperkalemia • Difficult airway should be anticipated based upon an airway exam (small mouth opening), neck rigidity.

Maintenance

• Lower anesthetic requirements • Opioids: Fentanyl and morphine have been shown to cause muscle rigidity and alfentanil can result in an acute dystonic reaction; these effects can be reversed with naloxone. Meperidine is contraindicated with selegiline (MAO inhibitor) and can cause hyperthermia and muscle rigidity. Remifentanil has been shown to suppress tremor. • Volatile anesthetics: Can inhibit dopamine reuptake and increase spontaneous and depolarization-evoked dopamine release. Halothane can cause arrhythmias due to sensitization of the heart to catecholamines. Isoflurane, enflurane, sevoflurane, and desflurane have been shown to be clinically safe; however, pre-existing hypotension may be amplified through peripheral vasodilation. • Muscle relaxants: Non-depolarizing agents have been shown to be clinically safe. • Dexmedetomidine has been shown to be well suited, even during DBS placement; however, it has a risk for hypotension.

Extubation/Emergence

• Postoperative nausea and vomiting may be treated with 5-HT3A medications or steroids. Avoid antidopaminergics such as butyrophenones (haloperidol and droperidol), phenothiazines, and metoclopramide can reverse dopamine effects in the basal ganglia and are contraindicated. • Laryngospasm due to hypersecretion: Consider glycopyrrolate to decrease secretions and avoidance of coughing during emergence. • Airway obstruction secondary to pharyngeal muscle discoordination. • Delirium with confusion and hallucinations

FOLLOW-UP BED ACUITY

ICU bed if the patient requires postoperative intubation, or may need reintubation. MEDICATIONS/LAB STUDIES/CONSULTS • NSAIDs: Good adjuncts

• Resume Parkinson’s medications as soon as possible; may be necessary to place an NG tube for administration

COMPLICATIONS

• Severe hypotension • Aspiration, respiratory failure, respiratory insufficiency due to impaired cough reflex • Psychosis: Low-dose benzodiazepines or neuroleptics (clozapine, but also olanzapine, risperidone, and quetiapine) • Post-extubation laryngospasm • Drug–drug interaction with additive effects on blood pressure and with MAOI

REFERENCES

1. ew M.Overview of Parkinson’s disease. Pharmacotherapy. 2007;27(12 Pt 2):155S–160S. 2. Bekris LM. The genetics of Parkinson disease. J Geriatr Psychiatry Neurol. 2010;23(4):228– 242. 3. Gárdián G, Vécsei L. Medical treatment of Parkinson’s disease: today and the future. Int J Clin Pharmacol Ther. 2010;48(10):633–642. 4. Nicholson G, Pereira AC, Hall GM. Parkinson’s disease and anaesthesia. Br J Anaesth. 2002;89:904–916.

ADDITIONAL READING

• Kalenka A, Schwarz A. Anaesthesia and Parkinson’s disease: How to manage with new Therapies. Curr Opin Anaesthesiol. 2009;22:419–424. • Gagne JJ, Power MC. Anti-inflammatory drugs and risk of Parkinson disease: A metaanalysis. Neurology. 2010;74(12):995–1002.

See Also (Topic, Algorithm, Electronic Media Element) • Alzheimer’s disease • Postoperative pulmonary complications

CODES ICD9 332.0 Paralysis agitans ICD10 G20 Parkinson’s disease

CLINICAL PEARLS

• Thorough preoperative assessment is indispensable. • In non-Parkinson surgery, drug therapy needs to be maintained precisely. • For longer surgeries, levodopa may be administered via a gastric tube or apomorphine can

be given subcutaneously (with antiemetic). • Precipitating factors and drugs need to be avoided. • Substantial additive effects on pre-existing arterial hypotension through anesthetics are common. • Avoiding respiratory complication (especially aspiration), should be a key anesthetic goal.

PARTIAL PRESSURES Priti G. Dalal, MD, FRCA Dmitri Bezinover, MD, PhD

BASICS DESCRIPTION

• There are 3 states of matter: Solid, liquid, and gas. Matter, regardless of its state, is composed of atoms and molecules (molecular theory) (1,2). – Solids (drugs and electrolytes) and liquids (water) achieve equilibrium by diffusion based upon concentration gradients or differences. – Gases achieve equilibrium based upon partial pressure gradients or differences. • The partial pressure of a gas describes the pressure exerted by those gas molecules against the walls that it is contained within (e.g. alveoli, anesthetic circuit, blood vessels). • Perioperatively, the anesthesia provider and intensivist utilize the concept of partial pressures to describe gas molecules in air (alveoli) as well as liquid (blood). PHYSIOLOGY PRINCIPLES

• Molecules dissolved in a liquid are described as “concentrations”: The amount or mass of the particular molecule per a specified volume (e.g. mg/mL, g/L) (1,2). – Molecules in plasma and extracellular fluid attain equilibrium based upon their concentration gradient; drugs, and electrolytes distribute in this manner. • Molecules in the gaseous state, however, possess a high kinetic energy, low density and viscosity, as well as the ability to expand indefinitely. – Thus, the term “concentration” cannot be used to describe gases. – Instead, the term “partial pressure” is used to describe the “amount” or distribution of a particular gas molecule • Partial pressures implement the concept of volume and pressure – Volume describes the 3-dimensional area that molecules occupy whether solids, liquids and gases. – Since gas molecules expand indefinitely, volume cannot be used to accurately or completely describe the amount of gas. – Pressure, however, can be measured. Gas molecules in a closed container (defined volume) exert a measurable force against the walls of the container. • Partial pressures are used to describe a particular gas “concentration.” – In a mixture of gases, each gas bestows a “partial” contribution to the pressure and is termed the partial pressure of the gas. – It is a function of the number of molecules that exert pressure against the walls of the container (fraction). – Partial pressure gradients drive gas diffusion and the attainment of equilibrium. • In the alveoli and breathing circuit, each gas exerts a partial pressure against the walls that it is contained in (due to indefinite expansion) and based upon the number of molecules of

the particular gas. • In the blood, gas molecules are present either in the following states: – Gaseous form above the level of the liquid. Only gas molecules in their gaseous form exert a partial pressure; diffusion and equilibrium is based upon partial pressures. – Dissolved based upon their individual solubility characteristics. They do not exert a partial pressure, but are in equilibrium with molecules in their gas form – Bound to substances (hemoglobin, proteins); does not exert a partial pressure. – Transformed to form other compounds based on the chemical reaction; does not exert a partial pressure. – Oxygen and carbon dioxide in the blood are present in all the above-mentioned forms; however, they are usually measured and discussed as partial pressures (gaseous form). • Solubility affects the amount of gas dissolved in liquid (blood, cerebrospinal fluid, water) – The solubility coefficient (λ) is the milliliters of gas dissolved per milliliters of liquid per atmosphere (1 atm = 760 mm Hg) partial pressure of the gas at any given temperature. – In other words, gas solubility is directly proportional to the pressure of that gas above the surface of the solution. – Increased partial pressures “force” gas molecules into the solution – This is the concept behind carbonated beverages. Bottling is done under pressure to increase the carbon dioxide that is dissolved in solution. Thus, when the bottle is opened, the pressure above the solution decreases and carbon dioxide bubbles out or effervesces. Hyperbaric oxygen therapy also functions in this manner. • Temperature affects the amount of gas dissolved in liquid (blood, cerebrospinal fluid, water) – Increases in kinetic energy enhance the motion of molecules and breaks intermolecular bonds, allowing escape from solution. – This results in an increased total pressure of all gases (increased total force exerted against the walls of a container). – Critical temperature is the temperature above which a gas cannot be liquefied regardless of the pressure applied. The critical temperature of nitrous oxide is 36.5°C. Below an ambient temperature of 36.5°C, nitrous oxide exists as a heterogenous mixture of gas and liquid within a cylinder. The critical temperature for oxygen is −119°C. • Partition coefficient describes the ratio of concentrations of a substance in 2 heterogenous phases in equilibrium with each other; it is dependent upon the partial pressures and solubility of the gas in the 2 phases. Anesthesia providers frequently utilize this concept when discussing volatile agents (blood:gas, brain:blood, fat:blood, oil:gas ratios). • Oxygen enters the body as a gas via the alveoli. Blood in pulmonary capillary arteries “pick up” the oxygen and carry it to tissues bound to hemoglobin molecules or in the gaseous or dissolved forms. – Hemoglobin binds oxygen to form oxyhemoglobin. Each gram of normal hemoglobin molecule has a binding coefficient of 1.39 mL O2/dL. – Oxygen solubility in blood. At 37°C, O2 has a solubility coefficient of 0.003 mL O2/dL of blood/mm Hg PaO2. Thus, a normal blood gas PaO2 of ∼100 mm Hg equates to 0.3 mL

O2/dL of blood. This is based on Henry’s law of solubility of gases.

– Oxygen cascades down its partial pressure gradient from a PaO2 of ∼100 mm Hg in the

pulmonary capillaries and ultimately through the blood and tissue to the intracellular mitochondria (PO2 ∼ 2 mm Hg).

– Solubility and temperature: Increases in temperature result in increases in kinetic energy of the gas molecule and reduced solubility. Conversely, decreased temperature reduces the kinetic energy of the gas molecule and increases solubility. – Saturation or dissociation curves are used to describe oxygen and carbon dioxide in blood. It plots the concentration of the gas molecule in blood (y-axis) against the gas molecule’s partial pressure (x-axis).

DISEASE/PATHOPHYSIOLOGY

• Carotid and aortic body chemoreceptors carefully regulate respiratory function in response to changes in pH, PaO2, and PaCO2 (2,3). Hypoxemia, hypercapnia, and acidemia lead to an increase in chemoreceptor activation and receptor firing; ultimately serving to increase minute ventilation. The threshold for chemoreceptor activation is a PaO2 < 80 mm Hg, PaCO2 > 40 mm Hg, or pH < 7.4.

• Absorption atelectasis (3): The tendency for airways to collapse if proximally obstructed in the setting of 100% oxygen administration. – Alveolar space primarily consists of oxygen and nitrogen. In the setting of proximal airway obstruction, the alveolar gases diffuse into the blood along their concentration gradient. The diffusion of nitrogen is limited by its poor solubility in plasma and thus it remains in the alveolar space (functions as a “space holder”). – In the setting of a high inspired concentration of oxygen and/or nitrous oxide, the “splinting” or “stenting” effects of nitrogen are lost and absorption atelectasis can occur. • Nitrous oxide expansion of an enclosed space. Air is composed of nitrogen (79%) and oxygen (21%). Nitrous oxide is poorly soluble in blood and will rapidly enter air spaces to reach equilibrium. However, nitrogen is 20 times less soluble in blood than nitrous oxide, and slowly diffuses/exits out of an air space into blood to reach a new equilibrium. Consequently, air spaces can increase in size (e.g., bowel causing difficulty with surgical visualization or closure); and closed air space expansion may be harmful (e.g., endotracheal tube cuff tracheal ischemia, venous air embolism enlargement, pneumothorax expansion, etc). • Diffusion hypoxia: When a low FiO2 is inhaled at the conclusion of a nitrous oxide anesthetic, an abrupt decrease in alveolar oxygen tension can occur. Nitrous oxide diffuses from the blood into the alveoli, diluting the oxygen available for pulmonary gas exchange. • Concentrating effect: Increasing the inspired concentration of a gas increases both the alveolar concentration and the rate of rise (FA/Fi) of alveolar concentration.

– If 50% of an inhalation anesthetic is taken up by the pulmonary circulation, an inspired concentration of 20% (20 parts of anesthetic in a total volume of 100 parts gas) will result in an alveolar concentration of 11% (10 parts anesthetic in a remaining gas volume of 90 parts). – If the inspired concentration is increased to 80%, and the pulmonary uptake is unchanged at 50%, the resulting alveolar concentration will be 67% (40 parts of anesthetic remaining in a total volume of 60 parts of gas).

PERIOPERATIVE RELEVANCE

• Calculating the contents of a nitrous oxide cylinder using the cylinder weight and Avogadro’s law (1): – The molecular weight of nitrous oxide is 44 g and a full nitrous oxide cylinder weighs 3.4 kg. According to Avogadro’s hypothesis, 1 mole of nitrous oxide weighs 44 g and 1 mole of nitrous oxide occupies 22.4 L. Therefore, 3.4 kg (3400 g) of nitrous oxide will occupy 1730 L ([3400 g/44 g] × 22.4 L). • Vaporizers and altitude change: Vaporizers deliver a set percentage of saturated vapor pressure to the fresh gas flow. Every potent inhalation anesthetic has a different saturated vapor pressure, which is independent of atmospheric pressure. – In areas of higher altitude, and thus lower atmospheric pressure, (i.e., Denver, Colorado), the saturated vapor pressure of a particular inhalational agent will contribute a higher percentage of the total pressure (Dalton’s law). Thus, for a given percentage of anesthetic administered, the partial pressure and depth of anesthesia should be greater. – In areas of lower altitudes, and thus higher atmospheric pressure (i.e., Death Valley), the vapor pressure contributes to a lesser percentage of the total pressure. The output for a given percentage setting on the vaporizer is reduced. • The alveolar gas equation allows a determination of the composition of alveolar gases. The inspired air in the alveoli is mainly composed of nitrogen (79%), oxygen (21%), carbon dioxide (0.03%), and water vapor. Based on Dalton’s and Henry’s law, at one atmospheric pressure of 760 mm Hg: The partial pressure of oxygen in dry air is 0.21 × 760 = 160 mm Hg. – The partial pressure of water vapor at one atmosphere when the air is fully saturated with vapor is 47 mm Hg. Inspired air that is fully saturated with water vapor reaching the lungs has a partial pressure = PatmO2 – Patm H2O = 160−47 = 113 mm Hg. – The Alveolar partial pressure of oxygen at room air may be calculated using the Alveolar Gas equation: PAO2 = PiO2–(PaCO2/R), where PAO2 = partial pressure of oxygen in the

alveolar gas; PiO2 = partial pressure of oxygen in the inspired gas; PaCO2 = pressure of

carbon dioxide in the artery, R = respiratory quotient – The Alveolar partial pressure at varying FiO2 can be calculated as follows: PAO2 = [(Pbaro – PH20)(FiO2) – PaCO2/R]

• Blood gas analysis: Measures the partial pressure of the gases in the arterial or venous blood that mainly include carbon dioxide and oxygen. The partial pressure of a gas in the blood determines the amount of gas that may be dissolved in the blood and attached to hemoglobin, and hence available to tissue. Alpha stat and pH stat are discussed at length elsewhere. • Hyperbaric oxygen chamber has 2 components that increase oxygen delivery: Increased hydrostatic pressure and increased oxygen pressure. The hydrostatic pressure reduces bubble volume, and the absence of inspired nitrogen increases the gradient for elimination of nitrogen and reduces hypoxia in downstream tissues. Increased oxygen pressure at the tissue level is the primary therapeutic goal. At 1.3 atm, the Alveolar gas equation is as follows: [{(760 × 1.3) – (47)}FiO2 – (PACO2/0.8)]

• Deep sea divers suffer from a condition called ‘Bends’ if they do not readjust slowly to the lower pressure at the surface (1). Deep sea divers breathe compressed air and are subject to high pressures when submerged; thus, the amount of nitrogen dissolved in blood and other tissues increases. If the diver returns to the surface too rapidly, the nitrogen forms bubbles in the blood as it becomes less soluble due to a decrease in pressure. The nitrogen bubbles can cause great pain and possibly death. To alleviate this problem, artificial breathing mixtures of oxygen and helium are used. Helium is only 1/5th as soluble in blood as nitrogen. As a result, there is less dissolved gas to form bubbles. Treatment with hyperbaric oxygen serves to “re-pressurize” the bubbles and dissolve them back into the blood.

EQUATIONS

• Ideal gas law. PV = nRT (1) • Boyle’s law. P1V1 = P2V2

• Charles’ law. V1/T1 = V2/T2

• Third gas law. P1/T1 = P2/T2

• Avogadro’s law. V1/n1 = V2/n2

• Dalton’s law. PT = Pa + Pb+ Pc

• Henry’s law of solubility. Pi = k × Ci

REFERENCES

1. avis PD, Kenny GNC. Basic Physics and Measurement in Anaesthesia, 5th edition, Butterworth-Heinemann; 2003. 2. anong WF. Review of Medical Physiology. 22nd edition, copyright © The McGraw-Hill Companies, Inc. 2005.

REFERENCES

3. West JB. Respiratory physiology, the essentials; 8th edition, copyright © Lippincott Williams and Wilkins; 2008. See Also (Topic, Algorithm, Electronic Media Element) • Hyperbaric Oxygen Therapy • PaO2 • PaCO2 • Arterial blood gases • pH Measurements

CLINICAL PEARLS

• Partial pressure is defined as the pressure exerted by a gas on the walls of the enclosed space in a mixture of gases. • The amount of gas dissolved is based upon the gas molecule, the liquid, the partial pressure of the gas, and the temperature.

PARTIAL THROMBOPLASTIN TIME (PTT) Parisa Partownavid, MD

BASICS DESCRIPTION

• PTT is a screening test for hemostasis and is one of the most frequently ordered tests in coagulation medicine. • PTT measures the integrity of the intrinsic and final common pathways of the coagulation cascade (Figure 1).

FIGURE 1. Schematic of coagulation cascade. HMWK = high-molecular-weight kininogen; PK = prekallikrein.

FIGURE 2. Approach to a prolonged PTT.

• It represents the time (in seconds) for the patient’s plasma to clot after the addition of phospholipid (an intrinsic pathway activator) and calcium.

PHYSIOLOGY PRINCIPLES

• PTT measures coagulation factors in the intrinsic and common pathways. These factors (in order of their role in the coagulation cascade) are: – High-molecular-weight kininogen (HMWK) – Prekallikrein (PK) – Factor XII – Factor XI – Factor IX – Factor VIII – Factor V – Factor X – Factor II – Fibrinogen • Normal range: depends on the reagent and instrument combinations each laboratory uses.

PHYSIOLOGY/PATHOPHYSIOLOGY

– Deficiencies or inhibitors of clotting factors within the intrinsic and final common pathways result in prolongation of the PTT. Etiologies can result from: – Anticoagulation: Heparin, low-molecular-weight heparins, warfarins. – Systemic disease – Coagulation factor deficiencies – Presence of an inhibitor – Artificial causes • Anticoagulation – Heparin binds to antithrombin III, causing a conformational change that accelerates its action 1000–3000-fold. Activated antithrombin III inactivates thrombin and Factor X (common pathway) that clot blood; dose-related prolongation of PTT is seen. – Low-molecular weight heparins (LMWHs) accelerate anti-factor X activity and can cause a mild prolongation of PTT (rarely <40 seconds) – Warfarin inhibits vitamin K epoxide reductase which is responsible for Factor II, VII, IX, and X (common, instrinsic, extrinsic pathway). • Systemic disease: – Liver disease: All coagulation factors are made in the liver except for vWF. Thus, the PTT time is a good indicator of liver metabolic function. It should be noted, however, that the PT is a better indicator of early liver failure; factor VII, which is a part of the extrinsic pathway, has the shortest half-life and is affected first. – Connective tissue disease: Lupus anticoagulants. – Amyloidosis: Factor X deficiency. – Myeloproliferative disease: Factor V deficiency. – Disseminated intravascular coagulation and fibrinolysis. • Coagulation factor deficiency: – Hemophilia A: X-linked recessive transmission of Factor VIII deficiency.

– Hemophilia B: X-linked recessive transmission of Factor IX deficiency. – Hemophilia C: Factor XI. – Factor II, V, X: Autosomal inheritance. – von Willebrand’s disease: A hereditary or acquired coagulation abnormality that can result in a qualitative or quantitative deficiency of von Willebrand factor (vWF). vWF is a protein required for platelet adhesion. As von Willebrand’s disease may be accompanied by factor VIII deficiency, PTT could be prolonged in these patients. • Presence of an inhibitor: – Specific factor inhibitor: Directed against specific clotting factors (e.g., factor VIII or factor V inhibitor) or excess heparin in the specimen (blood collected from heparinized catheter). – Nonspecific inhibitors (e.g., lupus anticoagulants). • Artificial causes: – Lipemic, icteric, and hemolyzed plasma samples (interferes with light transmission) – High hematocrit in patients with erythrocytosis (more plasma to anticoagulant ratio) – Even in the absence of the above conditions the test needs to be repeated.

PERIOPERATIVE RELEVANCE

• Prolonged PTT in the perioperative period: – Nasal airway/intubation is generally avoided in the presence of a coagulopathy. – Esophageal and gastric instrumentation should be minimized due to the risk of bleeding. – Central line placement in the thorax can result in life-threatening hemothorax. Adequate compression of large vessels in the event of arterial or venous bleeding is difficult, if not impossible. If placement is attempted in the neck, ultrasound technique may reduce inadvertent carotid artery puncture. • Prolonged PTT and neuraxial anesthesia techniques can increase the risk of bleeding around the spinal cord. – It is considered the most significant hemorrhagic complication in regional anesthesia due to the catastrophic nature of bleeding into a fixed and noncompressible space. – Incidence: Actual incidence of neurologic dysfunction from hemorrhagic complications associated with neuraxial blockade is unknown. Although the incidence cited in the literature is estimated to be <1 in 150,000 epidural placements and <1 in 220,000 spinal anesthetics, recent epidemiologic surveys suggest that the frequency is increasing and may be as high as 1 in 3,000 in some patient populations. – Management: The decision to perform spinal or epidural anesthesia/analgesia and the timing of catheter removal in a patient receiving antithrombotic therapy should be made on an individual basis. The risk of a spinal hematoma must be weighed against the benefits of regional anesthesia for a specific patient. If spinal or epidural needle/catheter placement is performed, the patient’s coagulation status should be optimized during placement, duration of epidural catheterization, and removal of the catheter. • In plexus and peripheral nerve blockade: – The associated risk of bleeding remains undefined. – Neurologic deficits: The expandable nature of the peripheral site decreases the chance of irreversible neural ischemia (unlike the epidural space). – Massive hemorrhage: Bleeding into the neurovascular sheath (especially in plexus blocks)

may result in a significant decrease in the hematocrit. – Incidence: Due to the rarity of the complications and lack of randomized studies, the information available is based on case reports. The overall incidence of bleeding complications associated with peripheral nerve blocks is low. – Management: The decision to perform peripheral nerve or plexus blocks (single injection or continuous catheter infusion) is at the discretion of the anesthesiologist after weighing the benefits of regional anesthesia against the risk of neural damage from hematoma or bleeding complications. In superficial limb blocks, anatomical landmarks are generally well defined or easily visualized with ultrasound imaging, and a developing hematoma can be easily accessed and compressed. On the other hand, bleeding complications may not be easily diagnosed in deeper blocks such as the posterior lumbar plexus block, especially with the use of a continuous catheter technique.

REFERENCES

1. amal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clinic Proceedings. 2007; 82(7):864–873. 2. Muilenburg DJ, Singh A, Torzilli G, et al. Surgery in the patient with liver disease. Anesthesiology Clinics. 2009;27(4):721–737. 3. Horlocker TT, Wedel DJ, Rolingson JC, Enneking FK, Kopp SL, Benzon HT, Brown DL, Heit JA, Mulroy MF, Roenquist RW, Tryba M, Yuan C. Regional anesthesia in the patient receiving anitthrombotic or thrombolytic therapy. American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Regional Anesthesia and Pain Medicine. 2010;35(1):64–101. 4. Ho M, Ganapathy S. Is peripheral/plexus block safe in the anticoagulated patient? Techniques in Regional Anesthesia and Pain Management. 2006:10:56–61. See Also (Topic, Algorithm, Electronic Media Element) • Epidural Hematoma • Prothrombin Time (PT) • Cirrhosis

CLINICAL PEARLS

• Routine coagulation studies are not indicated unless clinical or medication history suggests the potential for a coagulopathy. • It is important to recognize bleeding disorders that will not be detected by PTT assays. These disorders include: – Qualitative and quantitative platelet defects, which require specialized platelet function testing. – von Willebrand disease, which requires assays for von Willebrand factor. – Factor XIII deficiency, which requires specialized factor XIII screening or functional assays. – Deficiency of plasminogen activator inhibitor 1, which requires specific assays.

PATENT DUCTUS ARTERIOSUS Kimberly Howard-Quijano, MD Swati Patel, MD

BASICS DESCRIPTION

• In utero, the ductus arteriosus is a vascular connection that shunts blood from the main pulmonary artery (PA) to the descending aorta thereby decreasing pulmonary blood flow and increasing placental perfusion. • The ductus arteriosus closes functionally within 15 hours of birth and closes permanently 2– 3 weeks after birth. Spontaneous closure is brought on by increasing oxygen concentrations and decreased circulating placental prostaglandins. • Persistent patent ductus arteriosus (PDA) occurs when the ductus arteriosus fails to close after birth resulting in a pathologic left-to-right shunt from the aorta to the main PA.

EPIDEMIOLOGY Prevalence

• Term infants: 1 per 2,500 live births • Preterm infants: 33 per 100 live births • Spontaneous closure ∼0.6% per year

Prevalence

The National Birth Defects Prevention Network cites a wide range: 8–99 per 10,000 live births Morbidity

PDA in preterm infants is associated with bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), myocardial dysfunction, congestive heart failure (CHF), pre-renal azotemia, necrotizing enterocolitis, and interventricular hemorrhage. Mortality

Untreated PDAs have a mortality rate of approximately 1/3rd by 30 years of age and 2/3rd by 60 years of age. ETIOLOGY/RISK FACTORS

• More common in preterm infants. • Female to male ratio is 3:1. • Often present in complex congenital heart defects. It provides a source of blood flow between pulmonary and systemic circulations in infants with single ventricles prior to palliative interventions. • Can be associated with chromosomal abnormalities such as Down’s syndrome.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The ductus arteriosus closes spontaneously after birth in response to increased oxygen concentrations and decreased circulating placental prostaglandins including PGE2 and PGI2. The ductus arteriosus in preterm infants has been shown to have decreased sensitivity to oxygen concentrations and increased sensitivity to prostaglandins perhaps leading to an increased incidence of PDA in preterm infants. • PDA causes a left-to-right shunt at the level of the great arteries (aorta to main pulmonary artery). The amount of shunting depends on the size of the PDA and the ratio of resistances between the pulmonary and systemic vasculature. – The ratio of pulmonary vascular resistance (PVR) to systemic vascular resistance (SVR) is the driving force that determines the direction and volume of flow through the shunt. – The length and diameter of the PDA also affect shunt flow, with short and wide PDAs having the greatest flow. • A large PDA, and hence left-to-right shunt, causes increased PA blood flow, increased return from the pulmonary veins to the left atrium, pulmonary compliance, and if left untreated, eventually left heart failure, CHF, and CLD. – Over time, increased PVR can become irreversible, leading to pulmonary hypertension and right heart failure. – If PVR > SVR there can be a reversal of shunt (now right-to-left) leading to Eisenmenger’s syndrome (cyanosis, polycythemia). • A large PDA also causes a decrease in aortic diastolic BP due to backward flow of blood from the aorta to the PA during diastole or diastolic runoff. Diastolic runoff can lead to decreased coronary perfusion and myocardial ischemia. • The combination of CHF, myocardial ischemia, and diastolic runoff can lead to decreased cardiac output and systemic hypoperfusion putting the infant at risk for acidosis, renal failure, and necrotizing enterocolitis.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Anesthetic technique should depend on the patient’s presenting clinical condition, prematurity, birth weight, co-existing disease and surgical procedure. • Special attention should be given to maintaining adequate ventilation and cardiac perfusion.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Vary depending on the size of the PDA, severity of shunt, shunt direction, and range from asymptomatic to severe. • Increased work of breathing or shortness of breath, poor weight gain, feeding intolerance, fatigue, cyanosis, and decreased urinary output

History

• Birth history: pregnancy or birth complications, prematurity, and birth weight. • Past medical history: length of NICU stay, pulmonary status (history of intubation, length of intubation, BPD, CLD, recent chest x-ray), cardiovascular condition (history of other

congenital cardiac anomalies, recent EKG or echocardiogram), other congenital anomalies, and history of blood product transfusions. • Past surgical history and history of anesthesia or airway complications. • Family history of congenital anomalies or malignant hyperthermia. • Feeding history: growth retardation, failure to thrive. • Current clinical condition: Evidence of myocardial ischemia, systemic hypoperfusion, or respiratory insufficiency. When applicable, ventilator settings and endotracheal tube size and position as well as any problems ventilating patient, recent or current need for ionotropes, vascular access and invasive monitoring should be determined.

Signs/Physical Exam

• Tachycardia, tachypnea • Continuous machine-like heart murmur heard best at the left upper sternal border • Laterally displaced apical impulse • Widened pulse pressure, bounding pulses • Differential cyanosis and BP: Pre-ductal pulse oximetry and BP are often higher then postductal measurements • Patients with CHF may have signs of systemic hypoperfusion including diminished peripheral pulses, decreased capillary refill, hypotension, or acidosis.

TREATMENT HISTORY

• First-line treatment for failed spontaneous closure involves pharmacologic efforts with cyclooxygenase (COX) inhibitors (i.e., Ibuprofen or Indomethacin). • Surgical closure can also be performed via thoracotomy, VATS (video assisted thoracic surgery), or robot assisted VATS. • Transcatheter closure may be performed if the size and shape are amenable to device closure.

MEDICATIONS

As above (COX inhibitors)

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Arterial Blood Gas (ABG): may show cyanosis, hypoxemia, hypercapnia or acidosis. • CBC: Anemia, polycythemia if cyanosis present. • Comprehensive Metabolic Panel (CMP): Metabolic acidosis, pre-renal azotemia, hypoglycemia, or other electrolyte abnormalities. • Chest Radiography: Enlarged heart and increased pulmonary circulation. • Echocardiography: Presence of PDA, shunt direction, evidence of volume overload, myocardial function, other cardiac anomalies.

CONCOMITANT ORGAN DYSFUNCTION

• Lungs- BPD, CLD, increased PVR and decreased pulmonary compliance leading to increased work of breathing and difficulties ventilating patient. • Renal failure (pre-renal azotemia)

• Necrotizing enterocolitis • Interventricular hemorrhage

CIRCUMSTANCES TO DELAY/ CONDITIONS

• Unstable premature infants with poor feeding and difficult ventilation often require facilitated PDA closure in order to stop pulmonary over-circulation and improve feeding, weight gain, and extubation. If on high frequency oscillatory ventilation or too unstable for transport, PDA ligation can take place in the NICU at the bedside. • Acute illness (upper respiratory infection with fever or pneumonia) in stable outpatients that are undergoing elective closure may need to be delayed until resolution.

CLASSIFICATIONS

• Symptomatic or asymptomatic • Direction of the shunt (left-to-right versus right-to-left shunt).

TREATMENT PREOPERATIVE PREPARATION Premedications

Patients needing premedication (usually >6 months of age) may be premedicated with midazolam (0.05–0.1 mg/kg IV or 0.5–1.0 mg/kg PO) Special Concerns for Informed Consent

Premature infants and low birth weight infants are at increased risk for anesthetic and surgical complications as well as remaining intubated after surgery. INTRAOPERATIVE CARE Choice of Anesthesia

• Choice of anesthetic should depend on the clinical condition at the time of surgery, prematurity, birth weight, co-existing disease, and surgical procedure. General endotracheal anesthesia is always needed. • High spinal, epidural or caudal anesthesia in conjunction with general anesthesia may be used to provide postoperative pain control. Monitors

• Standard ASA monitors • Pre-ductal and post-ductal pulse oximetry. Pre-ductal measured in the right upper extremity. Post-ductal measured in the left upper or either of the lower extremities. • Invasive or non-invasive monitoring of the arterial BP in both pre-ductal and post-ductal locations; consider invasive monitoring if the patient has CHF or other co-existing conditions. • Central venous monitoring for patients with CHF or other co-existing conditions.

Induction/Airway Management

• Inhalational induction with sevoflurane is appropriate for stable patients without intravenous access. • Intravenous induction with fentanyl, muscle relaxants, and possibly etomidate is appropriate in severe or decompensated CHF patients who may not tolerate the cardiodepressent effects of inhalational anesthesia. • Prior to the start of surgery, patients should have adequate IV access and blood products available in order to treat possible intraoperative blood loss. • Hypothermia should be avoided by actively warming the patient as well as intravenous fluids and/or blood products.

Maintenance

• Inhalational anesthesia with sevoflurane is appropriate for stable patients. • Unstable patients with CHF or decreased myocardial function may not tolerate inhalational maintenance. Fentanyl and muscle relaxants can be used in conjunction with very low-dose sevoflurane. • A decrease in post-ductal pulse-oximetry is seen if either the aorta or the main pulmonary arteries are inadvertently ligated. • Blood pressures. The diastolic BP should increase after ductus ligation with cessation of diastolic run off to the lungs. If post-ductal BP decreases or is absent following duct ligation, the descending aorta may have been ligated. If a pre- and post-ductal BP gradient exists, an aortic coarctation may be present or was created operatively.

Extubation/Emergence

• Dependent on age, birth weight, co-existing disease, pre-operative clinical condition, and surgical course or complications. • Consider leaving intubated if already intubated prior to ligation (due to pulmonary overcirculation) or in premature infants with a history of CLF or PBD to optimize pain control, fluid, and ventilatory management. • Consider extubating if stable, not intubated before surgical repair, and uncomplicated surgical course.

FOLLOW-UP BED ACUITY

• Determined by age, weight, comorbidities, and post-operative condition. • Preterm infants often require at least 24-hour post-operative admission with apnea monitoring. • Symptomatic patients often require admission in either a neonatal or pediatric intensive care unit. • Asymptomatic patients or patients undergoing transcatheter closure may not necessarily require intensive care admission post-operatively and often can go home the same day after follow-up echo.

MEDICATIONS/LAB STUDIES/CONSULTS

• Dependent on age of patient, pre-operative status and/or other comorbidities. • CBC to evaluate hematocrit after surgical blood loss and intra-operative volume shifts. • Blood gas may be drawn to assess oxygenation and ventilation as well as possible postoperative acidosis.

COMPLICATIONS

• Complications if left untreated can include: Pulmonary hypertension, CHF, Eisenmenger’s syndrome, endocarditis, or arrhythmias. • Intraoperative complications may include: Hemorrhage, infection, damage to the left recurrent laryngeal nerve, pulmonary edema, or diaphragmatic paralysis from damage to the phrenic nerve.

REFERENCES

1. amrick S, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics. 2010;125:1020–1030. 2. Koch J, Hensley G, Roy L, et al. Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics. 2006;117(4):1113–1121. 3. Schneider DJ, Moore JW. Patent ductus arteriosus. Circulation. 2006;114(17):1873–1882. 4. Fortescue EB, Lock JE, Galvin T, McElhinney DB. To close or not to close: The very small patent ductus arteriosus. Congenital Heart Disease. 2010; 5(4):354–365.

ADDITIONAL READING

• Andropoulos DB, Stayer SA, Russell IA, Mossad EB. Anesthesia for Congenital Heart Disease. • Cote CJ, Lerman J, Todres ID. A Practice of Anesthesia for Infants and Children.

See Also (Topic, Algorithm, Electronic Media Element) • Fetal Cardiovascular Physiology • Atrial Septal Defect

CODES ICD9 747.0 Patent ductus arteriosus ICD10

Q25.0 Patent ductus arteriosus

CLINICAL PEARLS

• A persistent PDA causes a left-to-right shunt at the level of the great arteries leading to increased PVR, pulmonary edema, decreased pulmonary compliance, and left heart volume overload. • If left untreated, PDA can lead to myocardial dysfunction, CHF, pulmonary hypertension and

CLD. • Hypothermia, hypoxia, and acidosis in the neonate may temporarily increase PVR compared to SVR and cause shunt reversal with resultant cyanosis and decreased cardiac output.

PEDIATRIC CARDIAC PHYSIOLOGY Johanna C. Schwarzenberger, MD

BASICS DESCRIPTION

• Since cardiac catheterization is a difficult undertaking in the newborn and growing infant, most physiologic data about the cardiovascular system of the fetus, neonate, and pediatric patient is derived from invasive studies in sheep. Molecular function of the developing cardiac muscle has been investigated across many mammalian species, yet human data is lacking. • The pediatric cardiovascular system undergoes vast changes from fetal life to adolescence and knowledge about the specific developmental stages is crucial in understanding cardiovascular compromise in the pediatric patient. PHYSIOLOGY PRINCIPLES

• Series circulation. Following birth, the neonatal heart adapts to the new loading conditions resulting from a series circulation. As the lungs replace the low resistance placenta for gas exchange, the pulmonary vascular resistance drops continuously in the first days of life. Pulmonary blood flow becomes 20 times higher than during fetal circulation. In addition, the right ventricle is no longer exposed to the high afterload during fetal circulation. Remodeling of the pulmonary vascular bed occurs as a result of many factors: – Exposure to oxygen, a pulmonary vasodilator – Ventilation indirectly changes alveolar surface tension and thus affects perivascular tissue pressures – Changes in the metabolic milieu of the lung: Prostaglandins, bradykinins, histamine, angiotensin II • Cardiac output (CO). Overall CO per kilogram of body weight of the neonate is high when compared with the adult heart. In the newborn, CO reaches close to 200 mL/kg/minute. This high value mirrors the high oxygen consumption of neonates for processes such as thermoregulation, growth, and work of breathing. CO requirements are reduced to normal adult levels as lung mechanics become more effective in gas exchange. By adolescence, the CO is equivalent to that of an adult heart (2.5–3 liters/minute/m2). • Structural and cellular aspects of cardiac function – Fetal. Initially, neonatal myocytes contain immature myofibrils that are arranged in a disordered fashion featuring an incomplete sarcomere. To allow growth of the cardiac muscle, myocyte division during fetal life is traded for myocyte hypertrophy shortly after birth. In addition, the heart has an immature calcium transport due to an underdeveloped transverse tubular system and sarcoplasmic reticulum – Neonatal. At birth, developmental changes in myofibril size and structure begin and continue through childhood until their organized adult shape is attained. This involves: A reduction of the size of the nuclei but an increase in cellular mass.

With an increase of the cell surface area, the sarcolemma and T-tubule system develop after birth. Invagination of the T-tubule is vital for effective excitation-contraction coupling. Maturation of the sarcoplasmic reticulum and its calcium release channels occur at the same time as T-tubule development • Neonatal contractility. Despite the cellular development, the effective contractile mass of the neonatal myocardium is 50% that of the adult. As a result, the neonatal heart improves cardiac output by increasing heart rate rather than by improving its loading conditions with an increased preload. • Neonatal wall tension (a function of preload and afterload). The Frank Starling principle defines afterload as the weight against which myocardial fibers contract; decreases in afterload increase fiber shortening. In vivo, afterload is affected by the wall stress exerted onto the cardiac muscle as much as the impedance of the vasculature and the ejection pressure the heart has to pump against. LaPlace’s law defines wall stress: The circumferential wall stress (T) is equal to the pressure (P) times the radius (r) divided by twice the wall thickness (h). Consequently, afterload is also preload dependent. An increase in the left ventricular end diastolic volume increases the radius. It also affects the inertial mass against which the muscle has to pump. Venous return is determined by right atrial pressure. If right atrial pressure is increased, passive venous return has to overcome this pressure. In the pediatric heart, the left ventricular performance is reduced, making the restricted LV prone to ischemia and reperfusion injury. • The neonatal heart and the effects of neural, hormonal, and local mediators on vascular tone. – Neural innervation and responsiveness of the vasculature undergo developmental changes from the neonate to the adult. The sympathetic nervous system is incomplete at birth whereas the parasympathetic nervous system is complete. The developed systemic vasculature embraces a vast network of afferent and efferent signals with multiple effector site on the heart, smooth muscle vasculature, and endocrine system (e.g., adrenal gland). In addition, there are sophisticated feedback loops initiated by baroreceptors and chemoreceptors that are located in the carotid body, aortic arch, and atrial walls. – Local regulation of vascular tone occurs in response to hypoxemia, hypercarbia, low flow, and acidosis. The endothelium releases hormonal mediators with autocrine, paracrine, and endocrine action. Mediators include prostaglandin, nitric oxide, ATP sensitive potassium channels, and endothelin. – Glucocorticoid receptors also partake in maintaining vascular tone. Low cortisol may cause impaired cardiac performance and low vascular tone.

ANATOMY

• In utero the circulatory pattern is in parallel. There are 3 vascular beds (pulmonary, systemic, and placental) that are connected by shunts in the fetal circulation altering the specific tasks of the left and right ventricle compared to their work in adult life. The right ventricle performs two-thirds of the contractile work and thus becomes the dominant ventricle; it develops greater muscle mass compared to the left ventricle. – Placenta. Oxygenated blood from the placenta enters the umbilical veins and flows through the ductus venosus into the inferior vena cava to enter the right atrium.

– Right atrium. The cardiac output is divided to either pass through the open foramen ovale to the left atrium or through the tricuspid valve into the pulmonary vasculature. The majority of blood enters the left atrium and joins blood returning from the pulmonary veins which then passes through the mitral and aortic valve to the coronaries, ascending aorta, the head vessels and lastly through the descending aorta. Of the blood that enters the tricuspid valve, only 7% passes through the lungs due to the high vascular resistance; the remainder is shunted via the ductus arteriosus (PDA) to the descending aorta • At birth, the placenta is clamped and the foramen ovale and PDA are closed, thereby establishing an adult cardiac circulatory pattern that pumps blood in series.

DISEASE/PATHOPHYSIOLOGY

• A transitional circulation with right-to-left shunting through an open foramen ovale and/or PDA may persist in the presence of congenital heart disease or severe lung disease (meconium aspiration, diaphragmatic hernia, sepsis). It manifests clinically as hypoxia, hypercarbia, and acidosis. The underlying pathophysiology increases the pulmonary vascular resistance with resultant increases in right atrial pressures. This facilitates right-toleft intracardiac shunting via the patent foramen ovale as well as extra-cardiac shunting via the patent ductus arteriosus. • Congenital heart disease may present as: – Decreased systemic perfusion. Low systemic output may be either due to a failing systemic ventricle or a predominant left-to-right shunt resulting in Qp > Qs. – Tachypnea develops slowly as the pulmonary vascular resistance falls and the hemoglobin concentration declines. Decreased PVR results in increased pulmonary blood flow secondary to left-to-right shunting at the level of the heart or the great vessels. Physiologic anemia results from decreased erythropoietin levels in response to the relatively hyperoxic environment compared to in utero. – Cyanosis occurs when there is decreased pulmonary blood flow from right-to-left shunting (deoxygenated blood bypasses the lungs and enters the systemic circulation). • Hypercyanotic spells describe the acute reduction in pulmonary blood flow due to a variable outflow obstruction to the pulmonary vascular bed. This may be seen in infants with Tetralogy of Fallot and similar physiology. They present with abnormal respiratory pattern, severe cyanosis, and changes in the level of consciousness.

PERIOPERATIVE RELEVANCE

• As with the adult, adequate oxygen delivery to the tissues is dependent on systemic blood flow, hemoglobin concentration, and hemoglobin oxygen saturation. • Parameters that are unique to the pediatric heart include: – Bradycardic/parasympathetic response to stress. The neonate response to stress is via the parasympathetic system. Since neonatal cardiac performance is heart rate dependent, it is imperative that vagal stimulating procedures are either avoided or anticipated. Pretreatment with a parasympatholytic, such as atropine, is advisable. The impact of vagal stimulation is lessened by general anesthesia and deep ICU sedation. – The high sympathetic output state of the heart makes the neonate prone to cardiovascular compromise when using beta-blockers or inhalation anesthetics. – The neonatal heart improves cardiac output by increasing heart rate rather than by

increasing preload. However adequate preload must be maintained by reducing fasting periods and/or pre-operative intravenous fluid administration. – Inotropic support may be necessary to (re)establish the balance between venous return, optimal right atrial pressure, end diastolic ventricular pressure, and ventricular afterload. It should be noted that the response to inotropes may be decreased secondary to the incomplete development of the sympathetic nervous system. – Elevated levels of ionized calcium may be necessary for optimal cardiac performance in the neonatal heart. – Hypocortisolism should be considered in the young infant unresponsive to vasopressor therapy.

EQUATIONS

• Cardiac Output = Heart Rate × Stroke Volume • Systemic oxygen delivery = Systemic blood flow (Qs) × oxygen content of systemic arterial blood • LaPlace’s Law: T = (P × r)/2 h • Ohm’s Law: R = P/Q

GRAPHS/FIGURES

Table 1 Cardiovascular variables according to age (1)

REFERENCES

1. Flemming S, Thompson M, Stevens R, et al. Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: A systematic review of observational studies. Lancet. 2011;377(9770):1011–1018. 2. Rohan AJ, Golombek SG. Hypoxia in the term newborn: Part one-cardiopulmonary physiology and assessment. MCN Am J Matern Child Nurs. 2009; 34(2):106–112. 3. Blackburn S. Placental, fetal, and transitional circulation revisited. J Perinat Neonatal Nurs. 2006; 20(4):290–294. 4. Heymann MA. Control of the pulmonary circulation in the fetus and during transitional period to air breathing. Eur J Obstet Reprod Biol. 1999;84(2):127–132.

ADDITIONAL READING

• Artman M, Mahony L, Teitel DF. “Neonatal Cardiology" 2nd edition, 2011, McGraw-Hill • Rudolph AM. “Congenital Diseases of the Heart” 3rd edition, 2009, Wiley-Blackwell.

See Also (Topic, Algorithm, Electronic Media Element) • Cardiac Output • Afterload • Preload • Oxygen Content • Pediatric Respiratory Physiology

CLINICAL PEARLS

The newborn, immature heart compared to the adult, has: • A decrease in: – Force of contraction – Velocity of fibrous shortening – Response to exogenous catecholamines • Increased dependency upon increases in heart rate to enhance cardiac output. • Hypothermia in the neonate can severely compromise systemic perfusion. Since the newborn lacks the ability to shiver it resorts to thermogenesis in the brown fat. Neural input in response to hypothermia releases noradrenalin in brown fat resulting in the oxidation of triglyceride. This process increases oxygen consumption of the neonate, making it prone to lactic acid production (metabolic acidosis may ensue). Acidosis combined with the higher norepinephrine levels increases pulmonary vascular resistance. Hypothermia induced increases in PVR may revert the neonate’s circulation back to a transitional fetal circulation with the inability to oxygenate and to maintain adequate systemic perfusion.

PEDIATRIC RESPIRATORY PHYSIOLOGY Kimberly Howard-Quijano, MD Samuel H. Wald, MD

BASICS DESCRIPTION

• Pediatric patients have age-dependent respiratory physiology that changes with child development. The younger the patient, the greater the variance from adult physiology. • In general, pediatric patients have: – Increased respiratory rate – Increased oxygen (O2) consumption

– Increased airway resistance – Decreased functional residual capacity (FRC) – Decreased lung compliance – No change in tidal volumes or dead space per kg • The increased compliance and shape of the neonatal chest leads to increased work of breathing and decreased FRC. This, in conjunction with increased O2 consumption, can lead to rapid desaturation during periods of apnea. • Infant and toddler respiratory systems continue to develop until approximately 10 years of age. • Anatomical differences between the pediatric and adult airways as well as increased sensitivity to anesthetic-induced upper airway obstruction in neonates and infants may make mask ventilation and intubation more difficult. PHYSIOLOGY PRINCIPLES

– Compliance: – In utero, pulmonary respiration is performed by the low resistance placenta and the lungs remain “collapsed.” – At birth, pulmonary respiration shifts to the neonate’s lungs. The first breaths require large pressures (40–80 cm H2O) to overcome the surface forces needed to inflate the

lungs. Adequate surfactant, present in term infants, helps to decrease the inflation pressures. – Neonates and infants have decreased lung compliance (compared to older children and adults) due to the increased airway resistance caused by a relative paucity and immaturity of alveoli and decreased elastin. Alveoli maturation is not complete until 8–10 years of age. – In addition to decreased lung compliance, neonates also have increased chest wall compliance. This increased compliance is due to cartilaginous ribs and limited thoracic muscle mass. Less elastin leads to decreased chest wall recoil, decreased dynamic FRC, and increased work of breathing. As children grow, chest wall compliance decreases with

a resultant decrease in the work of breathing and an increase in the FRC. • FRC: Adult FRC is 50% of the total lung capacity (TLC); however, infants under general anesthesia have a FRC as low as 10–15% of the TLC. – When the FRC decreases to less than closing capacity, small airway closure occurs with tidal volume breathing, leading to worsened atelectasis, ventilation to perfusion mismatching, and decreased arterial O2 concentrations.

– The decrease in FRC caused by increased chest wall compliance is overcome in spontaneously ventilating infants by continued diaphragmatic activity in the early expiratory phase, relative tachypnea (with start of inspiration during preceding expiration to cause intrinsic PEEP), as well as sustained tonic activity of respiratory muscles. – Under general anesthesia, especially with muscle relaxants and paralysis, the compensatory mechanisms that neonates use to increase dynamic FRC are abolished, increasing the risk of atelectasis and respiratory insufficiency. • Ventilation: Neonates have an elevated respiratory rate that will gradually decrease to near adult levels by adolescence. – The carbon dioxide (CO2) response curve in neonates is shifted to the right and has a decreased slope. Thus, a higher arterial CO2 is required to stimulate an increase in minute

volume and the response is also dampened compared to older children and adults. – The slope of the CO2 response curve increases with postnatal age.

• Oxygenation: Neonates and infants have increased metabolism and O2 consumption.

– Neonates have a bimodal response to hypoxemia. Initially there is a transient increase in ventilation followed by a sustained decrease in ventilation. This decrease is believed to be secondary to direct suppression of the medullary respiratory centers and is more pronounced in premature infants. – The predominance of fetal hemoglobin (Hgb) in the neonatal circulation shifts the O2–Hgb

dissociation curve to the left. Hgb F has decreased 2,3-DPG causing increased Hgb–O2 affinity and a resultant left shift of the O2–Hgb dissociation curve with a lower P50 (partial

pressure of O2 at which Hgb is 50% saturated). Neonatal P50 = 19 mm Hg

3 months of age P50 = 27 mm Hg

9 months of age P50 peaks at 29–30 mm Hg Adult P50 = 27 mm Hg

– Increased concentrations of Hgb may be necessary to maintain adequate O2 delivery in neonatal patients.

ANATOMY

• The pediatric airway, especially in Neonates and infants have: Neonates and infants can be more technically challenging for mask ventilation and intubation due to the anatomical differences when compared to adult airways. – A proportionally larger occiput and tongue. – A more cephalad larynx (C2-C4 level compared to C6 in adults).

– A more anterior attachment of the vocal cords. – A long horse shoe-shaped epiglottis. – A short trachea and neck. • The cricoid cartilage is the narrowest point of a pediatric airway until approximately 5 years of age. In adults, the narrowest point is the glottis. • Infants are obligate nasal breathers until 5 months of age. • The neonatal chest wall is composed of cartilaginous ribs with a more horizontal attachment to the vertebral column. This causes increased chest wall compliance and less efficient ventilation with increased work of breathing. • Pediatric patients have much smaller absolute diameters of their upper and lower airways. Poiseuille’s law for laminar flow (R = 8 Ln/πr4, where R is resistance and r is radius) shows that even a small decrease in airway radius, when put to the fourth power, will cause a large reduction in airway caliber (1–2 mm of edema will cause a proportionately larger obstruction in pediatric patients versus adults, given the smaller diameter of their trachea and airways). DISEASE/PATHOPHYSIOLOGY

• Neonates and infants have periodic breathing at baseline. 80% of term infants and 100% preterm infants will have asymptomatic apnea of <10 seconds without cyanosis or bradycardia, most often during sleep. General anesthesia increases the frequency of periodic breathing or “postoperative apnea.” – The younger the infant, the greater the risk for postoperative apnea; premature infants have the greatest risk. After general anesthesia, neonates may require postoperative apnea monitoring for 24 hours depending on post conceptual age. – Factors associated with postoperative apnea include extent of surgery, anesthesia technique, anemia, and postoperative hypoxia. • Pediatric patients frequently suffer from upper respiratory infections (URI) and may present the day of surgery with recent history of URI. – During and up to 6 weeks following a URI, pediatric patients may have reactive airways and are more prone to bronchospasm, laryngospasm, and respiratory complications following general anesthesia. – Risk factors for respiratory complications in patients with/following URI: The younger the age of the patient. Active symptoms of fever, nasal congestion, rhinorrhea, or productive cough. History of reactive airway disease. • Laryngospasm: Sustained tight closure of the vocal cords by contraction of adductor muscles. More likely to occur in the setting of light anesthesia, recent or current URI, airway anomalies, ear/nose/throat procedures, hyperventilation with hypocapnia, and during induction or upon emergence. Treatment for laryngospasm includes increasing the depth of anesthesia, positive pressure ventilation, and/or muscle relaxation/paralysis. • Congenital syndromes can be associated with anatomical anomalies causing a more difficult mask ventilation or intubation. Syndromes known to be associated with difficult airways include: – Pierre Robin – Treacher Collins

– Goldenhar – Mucopolysaccharidosis – Down – Edwards – Freeman–Sheldon – Kenny–Caffey – Schwartz–Jampel – Cri du chat

PERIOPERATIVE RELEVANCE

• Infants are more prone to desaturation and hypoxia during induction of general anesthesia. – More sensitive to anesthetic-induced upper airway obstruction. – Decreased FRC and increased O2 consumption lead to rapid desaturation during periods of

apnea. • Pediatric airway anatomy can make mask ventilation and intubation more technically difficult. – Careful positioning and a shoulder roll can often improve mask ventilation and endotracheal intubation. – Proper mask size, an oral airway, and a chin lift or jaw distraction can improve mask ventilation. – Blade selection and endotracheal tube (ETT) size are important during pediatric intubation. ETT size can be approximated by [(Age in years)/4] + 4 Depth can be estimated by 3 × (ETT size) See Table 2 – Given that the narrowest point of the pediatric airway is the cricoid cartilage, which is past the glottis, it is important to check for an airway leak around the ETT at approximately 20–25 cm H2O to ensure that the ETT is not putting pressure on the trachea causing airway edema and possible postoperative croup or obstruction. • Barotrauma. The developing lung in neonates and infants are more prone to barotrauma. – While either pressure control (PC) or volume control (VC) ventilation can be used intraoperatively, PC is more commonly used to prevent barotrauma. • High concentrations of O2 can be damaging to neonates, especially premature neonates. – The lowest FiO2 possible to maintain adequate oxygenation should be used to prevent retinopathy of prematurity in susceptible neonates. – 100% FiO2 can lead to absorption atelectasis after 5 minutes of preoxygenation.

• Positive end expiratory pressure (PEEP) can help counteract the decrease in FRC in infants under general anesthesia. – PEEP of 6 cm H2O is recommended in children <6 months of age.

– PEEP of 6 cm H2O can also help combat absorption atelectasis caused by high concentrations of inspired O2.

• Premature infants are prone to more anesthetic complications including difficulty with

intubation, mask ventilation, and both intraoperative and postoperative ventilation. Premature neonates have: – A smaller airway, making intubation technically more difficult. – Decreased surfactant, immature alveoli, and small lower airway diameters that decrease lung compliance and ability to ventilate. – Immature chest wall development that can lead to decreased FRC. – Underdeveloped respiratory centers with a decreased hypoxic ventilatory response and higher apneic threshold. – The possibility of developing persistent pulmonary hypertension from chronic or frequent hypoxia and hypercapnia. Increased resistance to flow through the pulmonary vasculature can result in right-to-left shunting via the foramen ovale or ductus arteriosus. – Increased risk for postoperative apnea.

EQUATIONS

• ETT size = [(Age in years)/4] + 4 • Depth of ETT (cm) = 3 × ETT size • Poiseuille’s law for laminar flow: R = 8 Ln/πr4 – R = resistance – L = length – n = viscosity – r = radius

GRAPHS/ FIGURES

Table 1 Age-Related Pulmonary Physiology Table 2 Age-Related Airway Sizes

REFERENCES

1. Colin A, McEvoy C, Castile R. Respiratory morbidity and lung function in preterm infants 32–36 weeks gestational age. Pediatrics. 2010;126:115–128. 2. Von Ungern-Sternberg B, Regli A, Schibler A, et al. The impact of positive end-expiratory pressure on functional residual capacity and ventilation homogeneity impairment in anesthetized children exposed to high levels of inspired oxygen. Anesth Analg. 2007;104:1364–1368. 3. Flick R, Wilder R, Peiper S, et al. Risk factors for laryngospasm in children during general anesthesia. Paediatr Anaesth. 2008;18:289–296.

ADDITIONAL READING

• Cote CJ, Lerman J, Todres ID. A Practice of Anesthesia for Infants and Children. 4th ed. Philadelphia, PA: Elsevier; 2009.

See Also (Topic, Algorithm, Electronic Media Element) • Upper respiratory infection, preoperatively • Laryngospasm

• Work of breathing • Respiratory system compliance

CLINICAL PEARLS

• Pediatric patients have age-dependent respiratory physiology, with premature infant and neonatal physiology differing the most from adult respiratory physiology. – Increased O2 consumption – Decreased FRC leading to rapid O2 desaturation during periods of apnea

– Immature respiratory centers with decreased ventilatory responses to hypoxia, right shifting of the CO2 response curve, and decreased apneic threshold

– Increased risk for laryngospasm, postoperative apnea, and respiratory complications of general anesthesia. • Premature infants and neonates are at increased risk for laryngospasm, postoperative apnea, and respiratory complications of general anesthesia.

PERICARDIAL TAMPONADE Lori Gilbert, MD

BASICS DESCRIPTION

• Pericardial tamponade is a clinical syndrome caused by accumulation of fluid in the pericardial space; this creates an increase in intrapericardial pressure that restricts cardiac filling and decreases cardiac output. Tamponade can result from the accumulation of blood, pus, or air as a result of effusion, trauma, or rupture of the heart. • Cardiac tamponade can be due to slow or rapid compression of the heart. Large, slowly progressing chronic effusions are frequently well tolerated due to compensatory stretching of the pericardial sac. However, even with compensation, there is a critical point where the effusion reduces the volume of the cardiac chambers, increases intracavitary pressures, and causes drastic reduction in preload and cardiac output. Acute collections are a medical emergency and can be fatal if not quickly recognized and treated. EPIDEMIOLOGY Prevalence

• In the US: 2 cases per 10,000 people • In patients with large pericardial effusions (defined as >10 mm on echocardiogram), 35– 47% will progress to tamponade. • In patients with end-stage renal disease (ESRD), there is an increased incidence of pericarditis and pericardial effusions leading to tamponade. • Malignant effusions are the most common cause of pericardial tamponade.

Prevalence

• Most commonly seen in middle-aged and older populations. • Tamponade related to trauma or HIV is more common in young adults. • In regions endemic to tuberculosis, pericarditis is a prominent cause of effusion and tamponade. Mortality

Cardiac tamponade is an emergency; it is universally fatal if left untreated. ETIOLOGY/RISK FACTORS

• Idiopathic (large pericardial effusion) • Iatrogenic: Postcardiac surgery, electrophysiology procedures (atrial fibrillation and other ablations), percutaneous valve repair, percutaneous coronary intervention • Malignancy • Trauma • ESRD/uremia

• Aortic dissection • Drugs: Hydralazine, procainamide, isoniazid, minoxidil • Less common causes: Collagen vascular disease (lupus, scleroderma), tuberculosis, radiation, bacterial and fungal infections, HIV infection

PHYSIOLOGY/PATHOPHYSIOLOGY

• The pericardial sac consists of the visceral and parietal layers that surround the heart. The pericardial sac normally contains up to 50 mL of serous fluid that minimizes friction on the epicardium and thus helps to equalize hydrostatic pressures over the heart surface. Therefore, the pericardium has a small reserve volume and once the critical volume is reached, intracardiac filling pressures increase and diastolic volumes decrease. This results in a dramatic impairment of cardiac filling and a concomitant reduction in cardiac output. • In an effort to prevent chamber collapse, ventricular diastolic, right atrial, and wedge (left atrial) pressures all rise to equal pericardial pressures. This equalization of pressures is highly characteristic of tamponade. • Pulsus paradoxus is an exaggeration of the normal drop in systemic BP with inspiration (>10 mm Hg). With inspiration, there is increased venous return to the right, “full” heart. The increased volume pushes the intraatrial and intraventricular septums into the left heart. This results in decreased volumes of the left heart which manifests as a decrease in systemic cardiac output and a drop in systemic BP.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• “Full, fast, forward:" Avoid decreases in volume, bradycardia, vasodilation, and cardiac depression. The primary derangement is a decrease in stroke volume from impaired preload secondary to decreased ventricular chamber size. – Maintain filling pressures to overcome diastolic filling restrictions – Heart rate is a critical determinant of CO, as stroke volumes are significantly decreased (CO = SV × HR) – Increased vascular tone is necessary to maintain perfusion to the heart and brain, as SV/CO is decreased – Contractility is necessary to maintain efficient ejection of the stroke volume • Anesthetic technique should maintain a high sympathetic output until tamponade is relieved.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Dyspnea, tachycardia, tachypnea, chest pain, syncope • Weight loss, fatigue, anorexia may be seen in patients with malignancy or systemic disease • Musculoskeletal pain or fever may be present with connective tissue disorder • Night sweats, fever, weight loss can occur in patients with tuberculosis • Feeling of impending doom

History

• Recent cardiovascular surgery, coronary intervention, or trauma

• Malignancy • Renal failure (uremic pericarditis) • IV drug abuse or opportunistic infections (HIV) • Recent chest wall radiation • Lupus/drug-induced lupus • Recent pacemaker lead implantation

Signs/Physical Exam

• Elevated jugular venous pressure (JVP): Kussmaul’s sign describes a paradoxical rise in JVP on inspiration (instead of the normal decrease) • Pulsus paradoxus: Inspiratory systolic fall in arterial pressure of 10 mm Hg or more during normal breathing • Muffled heart tones • Hypotension, tachycardia; diaphoresis, dyspnea • Ewart’s sign: Bronchial breathing and dullness on percussion at the lower angle of the left scapula in pericardial effusion. • Y-descent on the central line waveform is abolished due to decreased diastolic filling of the ventricles (they are “full”). The X-descent is accentuated. TREATMENT HISTORY

• Needle pericardiocentesis may be performed to relieve intracardiac pressures; the use of imaging such as fluoroscopy, CT or echocardiographic techniques may be utilized. The most common approach for pericardiocentesis is the paraxiphoid, between the xiphoid and the left costal margin. • In hypotensive patients, volume expansion may be used as a temporizing measure; however, volume expansion in someone with active tamponade has been associated with increased intra-pericardial pressures, RA pressure and LV end-diastolic pressure. • Pericardiectomy (pericardial window) may also be indicated for hemodynamically unstable patients or in patients with recurrent tamponade. • Treat the underlying cause.

MEDICATIONS

• Ibuprofen, aspirin for pericarditis • Stomach acid reducer (H2 blocker, proton pump inhibitor)

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Doppler echocardiography can reveal chamber collapse of the right atrium, which may also be seen in hypovolemia without tamponade. Right ventricular collapse is a more specific finding for tamponade. • CXR • CBC to evaluate for infective or anemic causes • ESR to evaluate for inflammatory causes • Cardiac enzymes • ECG can reveal low voltage QRS complexes, PR segment depression, or electrical alternans,

which describes alternate-beat variation in the direction or amplitude of any ECG waveform segment. • Pericardiocentesis fluid for culture and cytology. • Cardiac catheterization (Swan–Ganz)

CONCOMITANT ORGAN DYSFUNCTION

• Renal failure (uremic pericarditis) • Pulmonary disease (e.g., tuberculosis) • Joint disease (e.g., lupus, rheumatoid arthritis) • Hypothyroidism

CIRCUMSTANCES TO DELAY/ CONDITIONS

Pericardiocentesis under local anesthesia prior to induction of general anesthesia with sternotomy. CLASSIFICATIONS

• Acute tamponade (immediately life threatening): Trauma, aortic rupture, or as a complication of an invasive diagnostic or therapeutic intervention. • Sub-acute tamponade (chronic): Malignancy, uremia, tuberculosis, or idiopathic pericarditis. Large amounts of pericardial fluid are tolerated until the critical ‘knee’ is reached on the pressure/volume curve of the heart. • Low pressure tamponade: Hemodialysis, traumatic hemorrhage, or over-diuresis; patients may be severely hypovolemic. Intracardiac and pericardial diastolic pressures are only 6 to 12 mm Hg. Patients may require a fluid challenge of 1 L isotonic saline to elicit tamponade dynamics.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Epinephrine or other vasopressors, inotropes/chronotropes may be needed. • Low-dose ketamine can be started with midazolam if local anesthesia with sedation is to be used. • Prep and drape the patient before induction if tamponade has not been relieved by needle pericardiocentesis. Special Concerns for Informed Consent

• In large, chronic effusions and minimal degrees of tamponade, the patient is often capable of giving consent on their own. • Acute tamponade is considered immediately life threatening and the decision to proceed is dictated by common sense even without formal consent. INTRAOPERATIVE CARE Choice of Anesthesia

• Local anesthesia with sedation to maintain spontaneous ventilation • General anesthesia with spontaneous ventilation • General anesthesia with positive pressure ventilation; surgeon must be prepared to emergently perform a sternotomy and relieve pressure.

Monitors

• Large bore IV access • Arterial line • Continuous transesophageal echocardiography (TEE) if possible to assess ventricular filling and contractility.

Induction/Airway Management

• General anesthesia with spontaneous ventilation: Mask induction with volatile agents and/or ketamine may be considered. • General anesthesia with positive pressure ventilation: Select agents that minimize depression of cardiac function and cause the least vasodilation and hypotension, such as ketamine or etomidate. Despite the benefit of maintaining spontaneous ventilation, patients are often induced, made apneic, intubated, and ventilated with positive pressure. When this occurs, the patient must be prepped and draped and the surgeons immediately prepared to perform a sternotomy. • Awake intubation that maintains spontaneous ventilation can lead to coughing or bucking, which increases intrathoracic pressure.

Maintenance

• Mechanical ventilation with positive pressure (increased intrathoracic pressures) will further decrease cardiac output by decreasing preload as well as increasing right ventricular afterload (decreases right ventricular outflow and forward flow). • Volume: Maintain filling pressures high enough to overcome diastolic filling restriction. CVP or PCWP may need to be >20–30 mm Hg. • Avoid vasodilation, bradycardia and maintain a high sympathetic output until tamponade is relieved. Inotropes and chronotropes may be needed

Extubation/ Emergence

• Patients are still at risk for pulmonary venous congestion or pulmonary edema from a sudden increase of pulmonary vascular return to the left atrium. • Patients with pre-existing left ventricular dysfunction, coronary artery disease, or valvular dysfunction should be observed. • Extubation is guided by individual cases: Traumatic, medical, or other causes of tamponade may lead one to keep the patient intubated depending on hemodynamics. • Treat hypertension appropriately.

FOLLOW-UP BED ACUITY

The patient should be sent to the ICU where adequate monitoring for signs of re-accumulation

of fluid, myocardial infarction, and other pathology can be observed and rapidly treated. MEDICATIONS/LAB STUDIES/CONSULTS

• EKG, echocardiogram • Treat sudden increases in SVR/hypertension • Cardiac enzymes • Consults: Cardiology, cardiothoracic surgery

COMPLICATIONS

A possible post-drainage complication is pulmonary edema, which occurs most frequently in patients with chronic pericardial effusion who have had large volume pericardiocentesis.

REFERENCES

1. O’Connor C, Tuman K. The Intraoperative management of patients with pericardial tamponade. Anesthesiol Clin. 2010;28:87–96. 2. Spodick DH. Acute cardiac tamponade. N Engl J Med. 2003;349:684–690. 3. Khandaker M, Espinosa RE, Nishimura RA, et al. Pericardial disease: Diagnosis and management. Mayo Clinic Proceedings. 2010;85(6):572–593. 4. Aye T, Milne B. Ketamine anesthesia for pericardial window in a patient with severe COPD. Can J Anesth. 2002;49(3):283–286.

ADDITIONAL READING

• www.cardiosource.org (American College of Cardiology)

See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary artery catheter waveforms • Uremia

CODES ICD9 423.3 Cardiac tamponade ICD10 I31.4 Cardiac tamponade

CLINICAL PEARLS

• The differential diagnosis for cardiac tamponade is constrictive pericarditis, pulmonary embolism, and tension pneumothorax.

PERIOPERATIVE BLINDNESS John L. Ard Jr., MD

BASICS DESCRIPTION

• Vision loss after nonocular surgery is a devastating complication that is most often associated with: – Spine surgery (1) – Cardiac surgery (1) – Head and neck operations (1) • The most common diagnoses include: – Posterior ischemic optic neuropathy (PION) – Anterior ischemic optic neuropathy (AION) – Central retinal artery occlusion (CRAO) – Occipital infarct (cortical blindness) • Although a minority of patients recover some partial vision, the improvement is often clinically insignificant. In addition, there are no proven treatment options. EPIDEMIOLOGY Prevalence

Depends on the type of surgery • Cardiac surgery: 8.64 cases/10,000 surgeries (2) • Spinal fusion: 3.09 cases/10,000 surgeries (2) • Appendectomy: 0.12 cases/10,000 surgeries (2) • Age range: 5–81 years • Male > female

Morbidity

Depends on the diagnosis • ION (anterior and posterior) – Usually bilateral, painless vision loss – Afferent pupil defect or nonreactive pupil – No light perception – Color vision is decreased or absent • CRAO – Unilateral vision loss – No light perception – Afferent pupil defect – After prone spine surgery, it is often associated with periorbital or eyelid edema, chemosis, proptosis, ptosis

• Cortical blindness – Patients have reduced vision with normal pupil reaction, intact corneal reflexes, and normal eye movement.

ETIOLOGY/RISK FACTORS

• Ischemic optic neuropathy (posterior): The etiology or cause of this complication is unknown but it is presumably a vascular injury caused by arterial hypoperfusion or possibly elevated venous pressures secondary to prone positioning and/or interstitial tissue edema. – Occurs most commonly in prone spine surgery of long duration (>6 hours) and large blood loss (>1 L). – Also occurs in cardiac surgery, head and neck surgery, but rarely in other types of surgery. – Other associated factors (not necessarily causative) Hypotension Anemia Excessive fluid administration Vasopressors Elevated venous pressure • Ischemic optic neuropathy (anterior): The etiology is unknown, but like posterior ION, it is presumably a vascular injury caused by arterial hypoperfusion or possibly elevated venous pressure. Occurs most frequently after cardiac surgery but can also occur in prone spine and head and neck surgeries (3). • Central retinal artery occlusion: Emboli are the usual cause in cardiac surgery; whereas direct pressure on the globe causes this injury in the prone spine surgery. • Cortical blindness: The etiology is ischemia and infarction involving the occipital lobe of the brain (where the visual cortex is located). It is either due to emboli that occur secondary to manipulation of the great vessels during cardiac or vascular surgery, or from hypoperfusion secondary to hypotension. The parieto-occipital region of the brain is a watershed zone for the middle cerebral and posterior cerebral arteries, and may undergo infarction during periods of systemic hypotension or if emboli block blood supply. Neuronal cell death is imminent after approximately 6 minutes of halted blood circulation. – Risk factors (4) Hypertension Diabetes mellitus Renal insufficiency Smoking history COPD Peripheral vascular disease Cardiac disease

PHYSIOLOGY/PATHOPHYSIOLOGY

• Normal anatomy of the optic nerve: – Contains myelinated axons that arise from the ganglion cells in the retina. • Nerve fibers traverse from (distal to proximal) – Head and ocular portions traverse the sclera – Orbital portion is ~3 cm in length

– Optic canal extends to the optic chiasm; it then travels through the brain – Visual cortex is found in the occipital lobe of the brain (final destination) – Arterial blood supply (subject to anatomic variation): Anterior to the lamina cribrosa: Derived from the short ciliary arteries Posterior to the lamina cribrosa: Derived from the circle of Zinn Orbital portion: Derived from the pial circulation which are end branches of the ophthalmic and retinal arteries. – Optic nerve venous drainage: The ocular and orbital portions flow primarily into the central retinal vein.

PREVENTATIVE MEASURES

• ION in prone spine surgery: Since the etiology is uncertain, preventive measures are speculative. – Colloids as well as crystalloids should be used for resuscitation in large blood loss cases (5)[C]. – Head should be positioned level with, or higher than, the heart, if possible (5)[C]. – Head should be in a neutral position (5)[C]. – Consider staging long spinal procedures (5)[C]. • CRAO – Prone spine surgery: Ensure proper positioning of the head with frequent eye checks to assure that the eyes are pressure free – Cardiac surgery: Efforts should be made to reduce the incidence of emboli during surgery

PREOPERATIVE ASSESSMENT • Patients should be evaluated in the immediate postoperative period. Vision loss usually manifests as soon as the patient is conscious. • Urgent ophthalmology consult is mandatory. – PION: Optic disk appears normal, initially. – AION: Optic disc edema and hemorrhages on fundoscopic examination. – CRAO: Macular/retinal edema, cherry red spot, or attenuated retinal vessels are typical on fundoscopic examination. • If diagnosis is not apparent after eye examination, then neurological imaging is in order, preferably MRI with gadolinium and stroke protocol technique (6)[C].

DIFFERENTIAL DIAGNOSIS Corneal abrasion

TREATMENT • ION (anterior and posterior) – Optimize hemoglobin levels, hemodynamic status, and oxygenation (5)[C]. – Agents that lower intraocular pressure like acetazolamide have been administered unsuccessfully.

• CRAO – Optimize hemoglobin levels, hemodynamic status, and oxygenation (5)[C]. • Cortical blindness – Increase oxygen delivery to the visual cortex by optimizing cerebral perfusion pressure and hematocrit (6)[C].

FOLLOW-UP As per ophthalmology

CLOSED CLAIMS DATA

• In 1999, the American Society of Anesthesiologists established the Postoperative Visual Loss Registry to investigate the mechanism of perioperative ION. • As of 2006, 93 spine surgery cases had been collected. – 83 cases were diagnosed with ION – 10 cases were diagnosed with CRAO

REFERENCES

1. ee LA, Roth S, Posner KL, et al. The American Society of Anesthesiologists Postoperative Visual Loss Registry: Analysis of 93 spine surgery cases with postoperative visual loss. Anesthesiology. 2006;105:652–659 2. Yang S, Drum M, Roth S. The prevalence of perioperative visual loss in the United States: A 10-year study from 1996 to 2005 of spinal, orthopedic, cardiac and general surgery. International Anesthesia Research Society. 2009;109:1534–1545. 3. Roth S. Perioperative visual loss: what do we know, what can we do? Br J Anaes. 2009;103:i31–i40. 4. Berg K, Harrison A, Lee M. Perioperative visual loss in ocular and nonocular surgery. Clin Ophthalmol. 2010;4:531–546. 5. American Society of Anesthesiologists Task Force on Perioperative Blindness. Practice advisory for perioperative visual loss associated with spine surgery. A report by the American Society of Anesthesiologists Task Force on Perioperative Blindness. Anesthesiology. 2006;104:1319–1328. 6. Newman NJ. Perioperative visual loss after nonocular surgeries. Am J Ophthalmol. 2008;145:604–610.

ADDITIONAL READING •

ASA Closed Claims Postoperative http://depts.washington.edu/asaccp/eye/index.shtml

See Also (Topic, Algorithm, Electronic Media Element) • Corneal abrasion

Visual

Loss

Registry:

CODES ICD9

• 362.31 Central retinal artery occlusion • 377.41 Ischemic optic neuropathy • 377.75 Cortical blindness ICD10 • H34.10 Central retinal artery occlusion, unspecified eye • H47.019 Ischemic optic neuropathy, unspecified eye • H47.619 Cortical blindness, unspecified side of brain

CLINICAL PEARLS

• Patients undergoing prolonged spinal surgery in the prone position with an expected large blood loss are at increased risk for postoperative blindness. – Consider informing these patients of the risk of visual loss in their preoperative visit. – Consider CVP monitoring. – Balanced colloid and crystalloid resuscitation. • Document positioning and eye checks on anesthesia record. • This injury occurs infrequently so it is difficult to study.

PERIOPERATIVE HYPERTENSION Cameron J. Ricks, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Hypertension: – Systolic BP >140 mm Hg – Diastolic BP >90 mm Hg • Hypertensive crisis or emergency: – Systolic BP >180 mm Hg – Diastolic BP >120 mm Hg – Accompanied by end-organ dysfunction such as hypertensive encephalopathy, intracerebral hemorrhage, subarachnoid hemorrhage, acute stroke, unstable angina, acute myocardial infarction, congestive heart failure, acute renal dysfunction, and acute aortic dissection. • Hypertensive urgency is defined as a severe elevation in BP without progressive end-organ dysfunction.

EPIDEMIOLOGY Prevalence

• In general, the worldwide prevalence of hypertension may be as high as 1 billion people. In the US, over 50 million people have BP warranting some form of treatment. • Primary hypertension: 90–95% • Secondary hypertension: 5–10%

Morbidity

Perioperatively: Diastolic BP >110 mm Hg has been shown to increase cardiac complications such as bradycardia, tachycardia, and ischemia. Mortality

• ∼7.1 million deaths can be attributed to hypertension worldwide. • Perioperatively, hypertensives have a 3.8 times increased odds ratio of postoperative death compared to normotensives. The 30-day postoperative cardiac mortality is 4 times that of age-matched controls. ETIOLOGY/RISK FACTORS

• Primary hypertension: Sedentary lifestyle, stress, obesity (in particular visceral), hypokalemia, salt sensitivity, alcohol intake, vitamin D deficiency, aging, family history. Other correlating factors include elevated renin, sympathetic nervous system overactivity, insulin resistance (Syndrome X or metabolic syndrome), and low birth weight.

• Secondary hypertension: Conditions that affect the kidneys, arteries, heart, or endocrine systems such as renal stenosis, coarctation of the aorta, pheochromocytoma, preeclampsia, and Cushing’s disease.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Systolic BP – Within the heart, it refers to the pressure during a cardiac contraction and requires invasive monitoring. – In the periphery, it can be measured with a non-invasive BP cuff. It measures the resultant pulsatile pressure against the peripheral vasculature from the blood ejected during cardiac systole. – Systole accounts for 1/3rd of the systole–diastole cycle. • Diastolic BP – Within the heart, it refers to the pressure of the relaxed ventricles. – In the peripheral vasculature, it refers to the tone of the arteries. • Mean arterial pressure is the average pressure in the heart and vasculature. It is calculated as follows, MAP = 2/3 (diastolic pressure) + 1/3 (systolic pressure). • Primary hypertension is not well understood. – During the early stages, there is increased cardiac output and normal total peripheral resistance. – With time, the cardiac output drops to normal levels, but the total peripheral resistance increases. – Theories include the inability of the kidneys to excrete sodium, causes natriuretic factor to increase (excretes sodium, but side effect is increased total peripheral resistance); overactive renin–angiotensin system causing vasoconstriction and retention of sodium and water (increased blood volume causes hypertension); and overactive sympathetic nervous system leading to increased stress response. – The end result is reduced intravascular volume and increased total peripheral resistance. – With time, this can lead to hemodynamic instability perioperatively (see below) and endorgan damage. Central nervous system (CNS) Cardiac Renal Retina Metabolic • Preoperatively: Patients can present with anxiety about the procedure/anesthesia or without taking their scheduled morning antihypertensive. • Intraoperatively: Induction often produces an exaggerated drop in BP attributed to the sympatholysis from induction medications combined with the intravascular hypovolemia from abnormal fluid regulation with hypertension (sympatholytics unmask the relative hypovolemia). Laryngoscopy often demonstrates an exaggerated increase in BP likely due to an exaggerated sympathetic response. Hypotension during maintenance often occurs from direct vascular dilation or sympatholysis. • Postoperative: The early post-anesthesia period is associated with pain-induced sympathetic stimulation, hypothermia, hypoxia, and intravascular volume overload. In addition, fluid

mobilization 24–48 hours postoperatively results in intravascular hypervolemia.

PREVENTATIVE MEASURES

• Preoperative evaluation to allay fears and concerns as well as advise about BP medications. – Preoperative clinic may allow the opportunity, if identified early enough, to optimize poorly controlled hypertension with the primary care physician – A phone call the night prior to surgery (along with proper instructions for antihypertensive medications on the morning of surgery), meeting preoperatively to discuss the operative course thoroughly, and home anxiolysis can aid in BP control. • Induction and laryngoscopy: Anticipate instability. These events occur back to back with widely different hemodynamic responses. – Propofol decreases preload, afterload, and contractility, hypotension may be avoided with slower and smaller doses. – Etomidate may provide more stable hemodynamics. A balanced induction with etomidate and propofol can avoid hypotension and hypertension. – Large narcotic doses can reduce induction medications and may blunt the sympathetic response to laryngoscopy. Although it preserves cardiac contractility, it may blunt sympathetic drive with resultant bradycardia and vasodilation. – Administration of vasopressors as appropriate; performing a laryngoscopy and intubation to “treat” hypotension prior to readiness is a poor practice. – Lidocaine IV or topical may blunt sympathetic response to laryngoscopy. – Volatile agents during bag mask ventilation can blunt sympathetic response. – Airway instrumentation should be performed quickly and effectively. – Preoperative placement of an arterial line or frequent BP cuff measurements (change frequency) may improve appropriate titration of medications. • Intraoperatively: Periods of low stimulation may be met with hypotension or a BP that precludes adequate perfusion of vital organs. – Assessment of volume status: NPO, maintenance, insensible and blood loss, other causes such as sepsis or anaphylaxis. Volume replacement should be performed; avoid overhydration which can result in postoperative fluid shifting. – Titrate narcotics and epidural boluses slowly to assess effects and have the opportunity to treat hypotension. – Heart rate, and rhythm should be optimized. – Reduction of volatile or TIVA while maintaining unconsciousness. – Nitrous oxide can maintain hemodynamics to a greater extent than volatile agents; additionally, it allows for “titrating down” volatile agents. – During stimulation, hypertensives may have an exaggerated response. Consider titrating short-acting medications, particularly if it is felt that the stimulation will be short lived (e.g., propofol, volatile agents, esmolol, nitroglycerine, calcium channel blockers). • Emergence: Consider titrating longer-acting antihypertensives if the patient’s BP starts increasing. Choices include metoprolol, labetalol, and hydralazine. • Postoperative: Orders for antihypertensive medications should identify titration parameters and appropriate dosing. If ineffective, consider alternative medications, telemetry, or ICU admission. Appropriate pain management should be provided (consider regional blocks, PCA, local infiltration, as appropriate). Pain, anxiety, delirium, hypoxia, and hypercarbia

can result in hypertension and should be appropriately managed.

PREOPERATIVE ASSESSMENT • Non-invasive BP cuff (forearm, arm, calf) and/or invasive arterial line (radial, brachial, axillary, femoral, dorsalis pedis). • Hypertensive crisis – CNS symptoms include motor, sensory, speech, visual defects from a stroke, or confusion, headache, and convulsions from hypertensive encephalopathy – Cardiac symptoms include angina, or angina equivalent (awake patient), EKG changes, drop in BP, arrhythmias, heart failure and desaturation – Renal: Hypertensive nephropathy – Retina: Hypertensive retinopathy – Metabolic: Elevated sugar levels

DIFFERENTIAL DIAGNOSIS

• Incorrect reading from poor technique, such as small cuff, or inappropriate placement. • Cushing’s response from increased intracranial pressure (an adaptive measure that increases the mean arterial pressure in order to preserve adequate cerebral perfusion; classically accompanied by bradycardia and irregular respirations).

TREATMENT • Confirm accuracy with a different limb, ascertaining correct cuff size and proper technique before administering therapy. • Determine baseline value from the patient, clinic documents, and/or preoperative evaluation. Assess for target organ damage as discussed above. • Hypertensive crisis/emergency – Cancel surgery – Place IV line – Treat with IV medications, boluses or drips; metoprolol, labetalol, hydralazine, diltiazem, or nitroglycerin. – Arrange for ER admission or direct admission to telemetry or ICU. It is the anaesthetist’s responsibility to coordinate a higher level or specialized care. Cancelling the case and telling the patient to follow up with their primary physician, check BP at home, take home medications, or drive to the emergency room may be construed as abandonment. In an ambulatory center, consider calling 911 for hospital transfer. – Consider arterial line placement. • Hypertensive urgency – Review antihypertensive medications. – Consider having patient take home medication with a small sip of water or administering the IV equivalent (metoprolol, hydralazine), or another IV antihypertensive. – Treat anxiolysis with good communication, discussion with the patient, and, if needed, anxiolytic medications.

– The decision to proceed with the surgery is dependent upon several factors: Urgency of the procedure (cancer diagnosis), BP measurement, other co-morbidities, anaesthetist’s personal experience, baseline BP, etc. • Induction and laryngoscopy are short-lived; derangements in BP should be treated with short-acting medications to avoid “ups and downs.” • Intraoperative: Consider phenylephrine, ephedrine or epinephrine boluses to temporize hypotension. If it is felt that the cause of hypotension is the profound reduction in systemic vascular resistance from volatile agents, consider phenylephrine infusion to provide alpha agonism and avoid “swings” in perfusion pressures. • Postoperative: The early post-anesthesia period can be associated with exaggerated sympathetic stimulation from pain, hypothermia, hypoxia, and volume overload. Focus on treatment of the cause.

FOLLOW-UP • Undiagnosed hypertension: Should follow up with their primary care physician for further work-up after procedure. • Hypertensive urgency: Should consider admission to the floor, telemetry, or the ICU for monitoring and treatment. • Hypertensive emergency: Should be treated immediately with IV medication to a goal of MAP reduction no more than 20% and transferred to the ICU for monitoring and IV BP control.

CLOSED CLAIMS DATA Not investigated

REFERENCES

1. eventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7 Report. JAMA. 2003;289:2560–2672. 2. ACC/AHA Guideline Update for Perioperative Cardiovascular Evaluation for Noncardiac Surgery (Committee to update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). J Am Coll Cardiol. 2002;39:542–553. 3. Marvik PE, Varon JV. Perioperative hypertension: a review of current and emerging therapeutic agents. J of Clin Anes. 2009;21:220–229.

ADDITIONAL READING

• Howell SJ, Sear JW, Foex P. Hypertension, hypertensive heart disease and periopeative cardiac risk. Br J Anaesth. 2004;92(4):570–583.

See Also (Topic, Algorithm, Electronic Media Element) • Hypertension • Intraoperative myocardial ischemia

CODES ICD9

• 401.9 Unspecified essential hypertension • 405.99 Other unspecified secondary hypertension ICD10

• I10 Essential (primary) hypertension • I15.9 Secondary hypertension, unspecified

CLINICAL PEARLS

• Careful consideration of the patient’s baseline BP as well as the urgency and type of surgery should be considered prior to case cancellation. • Hypercarbia, hypoxia, and pain are common intraoperative and postoperative causes of hypertension.

PERIOPERATIVE SEIZURES Wendy HP Ren, MD, FAAP

BASICS DESCRIPTION

• Perioperative seizures occur mostly in patients with a preexisting seizure disorder. In particular, those with: – Frequent seizures at baseline – Recent seizure activity – Multiple antiepileptic drugs (AEDs) • They can also occur in patients with metabolic derangements, local anesthetic systemic toxicity, or from anesthetic medications. Pathological processes that result in myoclonic movements may be misconstrued as a seizure. • Perioperative seizures have not been shown to be influenced by anesthesia type (general, MAC, regional) or procedure. EPIDEMIOLOGY Prevalence

• General population: Occurs in 0.03% for all patients undergoing all types of anesthesia. • Diagnosis of seizure disorder: Occurs in 2–5.8% undergoing all types of anesthesia. • Incidence is increased in the pediatric population as well as those who are intellectually and developmentally delayed. Prevalence

Related to the patient’s underlying condition, as opposed to the type of anesthesia. It is more likely to occur in patients who have frequent seizures, especially if they have had seizures close to the time of the procedure, and if they require multiple antiepileptic medications. Morbidity

• Perioperative seizures often resolve without medication. • Injury to the tongue, head, or extremities may result as well as aspiration of stomach contents. • Prolonged seizures may result in cerebral ischemia leading to coma and death.

ETIOLOGY/RISK FACTORS

• In the perioperative setting where patients are fasting and anxious, factors that may contribute to seizures include: – Antiepileptic medication noncompliance (missed or delayed dosing) – Altered gastrointestinal absorption of antiseizure medications – Electrolyte disturbances – Sleep deprivation

• Anesthetics with pro-convulsant potential: – Inhaled volatile anesthetics (e.g., enflurane, sevoflurane) with rapid changes in brain concentration – Local anesthetics (e.g., lidocaine, bupivacaine) have the potential to be pro-convulsant even at non-toxic levels. – Opioids (e.g., fentanyl, alfentanil, sufentanil, meperidine) – Sedative/hypnotic medications (e.g., propofol, etomidate, ketamine, methohexital) – Of note, despite the pro-convulsant potential, most anesthetics have both proconvulsant and anticonvulsant properties.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The mechanism of anesthetic effect on seizure threshold is speculated to be a result of an imbalance between excitatory and inhibitory neurotransmission. Most perioperative seizures occur at induction or emergence when anesthetic levels are changing rapidly. • The incidence of epilepsy is higher in the intellectually and developmentally disabled population, and there is increased morbidity and mortality in children with seizures and neurologic deficits. This group of patients tends to have more frequent seizures and often requires anesthesia for routine procedures (e.g., radiologic examinations and dental examinations and treatment) or procedures related to trauma incurred during a seizure that a healthy patient otherwise would not require. • Local anesthetic toxicity – The CNS is more sensitive to local anesthetics than the cardiovascular system. Classic early symptoms include circumoral numbness, metallic taste, lightheadedness, visual and auditory disturbances, agitation, or tremors. Later symptoms consist of seizures and coma. – First, a preferential blockade of the inhibitory CNS pathways leaves the excitatory pathways unopposed. This can manifest as shivering/muscle tremors and proceed to tonic–clonic seizures. With increasing plasma levels, both inhibitory and excitatory pathways are blocked. Generalized CNS depression ensues with potential respiratory arrest. – Potent, longer acting, and R(+) isomers of local anesthetics such as bupivacaine tend to be more toxic. – Hypoxia and hypercarbia can decrease the convulsive threshold. • Hypoglycemia can result in neuroglycopenia with headache, confusion, mental sluggishness, seizures, or coma. Patients at greatest risk are those receiving parenteral nutrition with dextrose-containing solutions that are abruptly stopped. Neonates require dextrose infusions because they lack glycogen stores due to hepatic immaturity. In addition, in diabetics, longacting insulin preparations and oral hypoglycemics can result in hypoglycemia when combined with NPO status. • Hypoxia leading to brain ischemia can present as seizures in addition to other neurologic deficits. • Electrolyte abnormalities such as hyponatremia and hypocalcemia have been reported to lower the seizure threshold. • Febrile seizures: There are no reports of this occurring under anesthesia. The pathogenesis involves a rapid rise in temperature, usually from a viral infection. Intraoperative temperatures do not rise that rapidly, especially when monitored.

PREVENTATIVE MEASURES

• Since patients with frequent seizures at baseline are at highest risk of having a seizure in the perioperative period, it is essential to be prepared to treat seizure activity regardless of the surgical procedure or anesthetic technique. In addition, avoid missing doses of AEDs and consider IV dosing if the patient is not tolerating PO intake. • Patients on parenteral nutrition with dextrose-containing solutions should have their infusions weaned and not stopped to avoid hypoglycemia. Consider more frequent blood sugar monitoring. • Diabetics should have their blood sugars checked prior to surgery as well as be instructed to hold long-acting insulin preparations and oral hypoglycemics. Ideally, their procedures should be scheduled early in the morning to avoid excessive fasting periods. • In patients with febrile seizure history, it is important to monitor temperature and treat with cooling measures and antipyretics when necessary (per oral or per rectal).

PREOPERATIVE ASSESSMENT • Initial diagnosis is usually on the basis of clinical signs: Tonic–clonic, tonic, clonic, or myoclonic movements that do not resolve. The seizure may be associated with a loss of consciousness and/or postictal sedation. • Status epilepticus is defined either as simple prolonged seizure, or recurrent seizures, with decreased consciousness for longer than 30 minutes.

DIFFERENTIAL DIAGNOSIS

• Delayed awakening should include the possibility of a postictal state, as well as: – Residual anesthetics (volatile, opioid, benzodiazepine, etc.) – Coma • “Seizure-like” or myoclonic activity may be the result of: – Rigors and shivering – Sepsis – Neuromuscular syndrome (NMS) – Malignant hyperthermia (MH) – Thyroid toxicosis – It should be noted that true seizures may also occur with NMS, MH, and thyroid toxicosis. • Anesthetic drug–induced myoclonic movements have an unknown pathogenesis and this symptomatic presentation differs from their proconvulsant effects.

TREATMENT • Perioperative seizures often resolve without therapy. • Although the cessation of seizure activity is critical, it is also important to discern treatable causes; for example, hypoxia, metabolic derangements, non-therapeutic AED levels. • Supportive measures include supplemental oxygen with facemask or assisting ventilation with a bag mask. Patients at risk for pulmonary aspiration should be placed in the lateral position. Consider padding areas of potential traumatic injury.

• Seizures lasting longer than 5 minutes can be treated with benzodiazepines. If this therapy fails, consider the administration of barbiturates or phenytoin. In patients with a history of epilepsy, the family or caregivers may have experience with treatment options that have been successful in the past. • The development of status epilepticus may require the induction and maintenance of general anesthesia to avoid brain ischemia and coma; consultation with a neurologist should be performed as soon as possible. Induction with intravenous medications (propofol, etomidate) should be followed by the placement and continuous monitoring of EEG. Although the classic teaching has been to utilize volatile agents for maintenance, there have been reports of the successful use of propofol, etomidate, and even ketamine. Muscle relaxants stop extremity movement and tongue biting and may be considered to decrease the risk of injury; however, it should be noted that they have no effect on stopping electrical seizure activity.

FOLLOW-UP Consider postoperative EEG monitoring if the patient continues to have seizures, as well as a neurology consultation.

REFERENCES

1. iesen AD, Jacob AK, Aho LE, et al. Perioperative seizures in patients with a history of a seizure disorder. Anesth Analg. 2010;111(3):729–735. 2. Benish SM, Cascino GD, Warner ME, et al. Effect of general anesthesia in patients with epilepsy: A population-based study. Epilepsy Behav. 2010;17(1):87–89. 3. Kopp SL, Wynd KP, Horlocker TT, et al. Regional blockade in patients with a history of a seizure disorder. Anesth Analg. 2009;109(1):272–278. 4. Cheng M, Tempelhoff R. Anesthesia and epilepsy. Curr Opin Anaesthesiol. 1999;12(5);523– 528. 5. Ren WH. Anesthetic management of epileptic pediatric patients. Int Anesthesiol Clin. 2009;47(3):101–116. See Also (Topic, Algorithm, Electronic Media Element) • Seizure disorders • Hypoglycemia • Hyponatremia • Local anesthetic systemic toxicity

CODES ICD9 780.39 Other convulsions

ICD10

R56.9 Unspecified convulsions

CLINICAL PEARLS

• Since patients with frequent seizures at baseline are at highest risk of having a seizure in the perioperative period, it is essential to be prepared to treat seizure activity regardless of the surgical procedure or anesthetic technique. • Perioperative seizures occur most commonly during induction and emergence. They often resolve without treatment. However, it is important to discern treatable causes; for example, hypoxia, metabolic derangements, non-therapeutic AEDs. Consider supportive care and injury prevention.

PERIOPERATIVE STATINS N. Matthew Decker, BS Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase; they are primarily indicated for the treatment of hypercholesterolemia and reducing low-density lipoprotein-cholesterol (LDL-C). • Statins have also been shown to possess several pleiotropic effects: – Improved vascular endothelial function – Immunomodulation – Stabilization of atheromatous plaques – Protection against thrombosis • In future investigations, indications for perioperative statin use are likely to be expanded and further delineated. PHYSIOLOGY PRINCIPLES

• Pharmacology: Primary role is the reduction of cholesterol synthesis. Statins competitively inhibit HMG-CoA reductase in the liver. HMG-CoA reductase catalyzes the synthesis of mevalonate, the rate-limiting step in cholesterol biosynthesis. • Decreases in hepatic intracellular cholesterol synthesis and release result in extrahepatic upregulation of LDL receptor expression on their cell surfaces, thereby increasing clearance of LDL and VLDL. • Pleiotropic effects – Improved endothelial function; impairments are closely associated with adverse outcomes. Hypercholesterolemia and atherosclerosis impair endothelium-dependent vasodilation and nitric oxide (NO) production. NO has several anti-inflammatory and anti-thrombotic effects that protect against chemokine expression, left ventricular remodeling and dysfunction, and thrombogenesis. – Immunomodulation: Statins decrease systemic inflammation and stabilize atheromatous plaques by reducing: LDL levels: Normal oxidative modification of LDL-C elicits an antigenic response by macrophages, strongly promoting inflammation. Interleukins (IL): The inflammatory process in atherosclerotic plaques produce inflammatory mediators (e.g., interleukin-6 [IL-6]) Tumor necrosis factor (TNF): A pro-inflammatory cytokine produced from atherosclerotic plaque-related inflammatory processes. C-reactive Protein (CRP): Produced by hepatocytes in response to IL-6 and TNF. CRP is a universal marker for inflammation, and is prognostic for coronary heart disease. – Protection against thrombosis: Statin therapy reduces platelet adhesion and inhibits

thrombogenesis. Venous thrombosis increases the risk of MI and stroke.

DISEASE/PATHOPHYSIOLOGY

• Adverse effects are rare and dose dependent. – Muscle damage: Rhabdomyolysis and myopathy (rare). More common when combined with fibrate therapy or used jointly with amiodarone or verapamil. – Mild transient proteinuria: There is no associated pattern of renal failure or injury. – Mild hepatotoxicity: Hepatic transaminase levels are elevated in 0.5–2.0% of patients; this is a dosedependent response (1)[A]. Abnormal liver function is typically clinically insignificant and progression to liver failure due to statin therapy is rare, if existent. Despite this evidence, cholestasis and acute liver disease are contraindications to statin therapy. – Teratogenicity has been described and therefore statins should not be used during pregnancy. – Diabetes mellitus: Slightly increases the risk of development. • Evidence of adverse effects due to perioperative statin exposure (muscle cramps or myalgias, jaundice, or hepatic tenderness) should be followed by testing for creatine kinase or liver function tests, and statins should be discontinued (2)[A].

PERIOPERATIVE RELEVANCE

• Cardiac protection – Perioperative MI Type I MI (coronary plaque rupture): Statin therapy has been shown to decrease the incidence by stabilizing coronary plaques and protect against rupture, thus reducing coronary thrombosis (2)[A]. Type II MI (due to oxygen supply/demand mismatch): Not affected by statin therapy. – Arrhythmias: Decreased incidence, likely via an anti-inflammatory process. Statin therapy has been shown to consistently and significantly protect against atrial fibrillation. However, there is inconclusive evidence indicating protection against ventricular fibrillation. – Valvular effects: Active inflammatory processes can lead to valvulitis and calcification. Inhibition of inflammation and stabilization of valvular endothelium is thought to inhibit progression of stenosis. Statin therapy is associated with a reduced incidence of both rheumatic aortic and mitral valve stenosis. There is conflicting evidence as to whether statin exposure influences postoperative morbidity and mortality (as measured by EuroSCORE risk of mortality and long-term survival rates) after valvular heart surgery (2). – All-cause mortality following cardiac surgery: Significantly decreased with both long-term treatment and immediate preoperative statin exposure. • Vascular protection – Thrombosis/venous adverse events are decreased. – Atherosclerosis

Therapy with rosuvastatin or atorvastatin reduced LDL ≥40%, the amount necessary to achieve atherosclerosis regression. Reasonable target LDL-C levels in high-risk patients are <70 mg/dL (2)[A]. – Abdominal aortic aneurysm (AAA): A meta-analysis correlates statin exposure with reduced expansion rates of small AAA, as well as improved outcomes in surgical and endovascular AAA repair. Likely due to immunomodulatory effects. – Carotid artery disease: Statins may slow progression or cause regression of intima-media thickness and decrease the rate of microemboli. Outcome studies have shown a reduction in stroke risk and cardiovascular events (1). – Peripheral artery disease: Statins have been shown to decrease the incidence of cardiac events, perioperative mortality, and renal dysfunction. • Renal protection – Percutaneous coronary interventions: Statin preloading has been shown to decrease contrast-induced nephropathy (CIN). – Major vascular surgery: Chronic use has been associated with decreased renal insufficiency and improved recovery rates from renal injury (2)[A]. The role of preloading is unclear. • Neuroprotection – Stroke: Observational studies demonstrate reduced frequency of stroke following major vascular surgery (3). When combined with beta-blockers, statin exposure reduced the incidence of stroke during CABG. – Encephalopathy: Evidence is currently inconclusive. • Other effects – Sepsis: Statins appear to play an adjuvant role via suppression of inflammation (reduced IL-6 and TNF levels) and antithrombotic effects. Meta-analyses correlate therapy with reduced infection and improved mortality rates during sepsis. Randomized trials are needed to develop applicable recommendations for use in sepsis. – Reactive airway disease: Statin exposure is linked with reduced bronchial hyperreactivity. • Perioperative strategy of beginning statin therapy: While there is evidence suggesting the beneficial effects of statin therapy in perioperative outcome, further evidence from randomized clinical trials is needed to develop a comprehensive strategy. At this time, dose, type, and duration of therapy need to be determined as well as differentiating between indications for high-risk and average-risk patients. – Indications: Currently only for treatment of high-risk cardiac patients. Should be combined with aspirin and titrated with a beta-blocker regimen in patients with ischemic heart disease (4)[A]. – Type: A meta-analysis of literature determined rosuvastatin or atorvastatin ≥20 mg/dL (potency: Rosuvastatin > atorvastatin > pravastatin > simvastatin) to be optimal (achieved target LDL-C levels) (1)[A]. Rosuvastatin has a similar risk-benefit profile as other statins, but its increased potency is advantageous due to the dose-dependent nature of adverse effects. Fluvastatin is less potent than rosuvastatin or atorvastatin. However, its longer half-life and extended release may make it preferable in patients unable to receive oral medications in the immediate postoperative period. It is not hepatically metabolized, so

it may be preferred in cases of hepatic injury (2)[A],(1)[B]. – Duration of therapy: Short-term therapy (≤7 days) initiated preoperatively in cardiac and vascular surgical patients is associated with a reduced incidence of adverse events. If possible, it has been suggested to administer the day of or the night before surgery to maximize potential benefits. A high loading dose immediately prior to percutaneous coronary intervention was also shown to reduce myocardial injury and major cardiac adverse events (1)[A]. • Discontinuation of statin therapy – Statin therapy should not be discontinued prior to open or endovascular procedures and should be resumed postoperatively as soon as possible. – Discontinuation after major vascular surgery has been shown to significantly increase incidence risk for cardiac death or recurrent MI (5). – A delay of >4 days in restarting therapy increased the risk of cardiac myonecrosis (related to duration of hospitalization and death) in treatment of infrarenal aneurysms (5)[B]. – Effects of statin withdrawal are related to severity of coronary artery disease.

Geriatric Considerations

There is evidence that perioperative statin treatment has a greater effect on outcome in older, high-risk patients than in younger patients.

REFERENCES

1. Paraskevas PI, Mikhailidis DP, Veith FJ. Optimal statin type and dosage for vascular patients. J Vasc Surg. 2011;53(3):837–844. 2. Singh N, Patel P, Wyckoff T, et al. Progress in perioperative medicine: focus on statins. J Cardiothorac Vasc Anes. 2010;24(5):892–896. 3. Liakopoulos OJ, Choi Y, Haldenwang PL, et al. Impact of preoperative statin therapy on postoperative adverse outcomes in patients undergoing cardiac surgery: A meta analysis of over 30000 patients. Eur Heart J. 2008;29(12):1548–1559. 4. Poldermans D, Bax JJ, Boersma E, et al. Guidelines for preoperative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery. Eur J Anaesthesiol. 2010;27:92–137. 5. Le Manach Y, Estevez CI, Bertrand M, et al. Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing vascular surgery. Anesthesiology. 2011:98–104.

ADDITIONAL READING

• Bouchard D, Carrier M, Demers P, et al. Statin in combination with beta-blocker therapy reduces postoperative stroke after coronary artery bypass graft surgery. Ann Thorac Surg. 2011;91:654–660. • Landmesser U, Drexler H. The clinical significance of endothelial dysfunction. Curr Opin Cardiol. 2005;20:547–551. • Quist-Paulsen P. Statins and inflammation: an update. Curr Opin Cardiol. 2010;25:399–405.

• Robinson JG, Smith B, Maheshwari N, et al. Pleiotropic effects of statins: Benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol. 2005;46:1855–1862.

See Also (Topic, Algorithm, Electronic Media Element) • Coronary artery disease • Liver function tests • Peripheral vascular disease • Aortic valve repair • Abdominal aortic aneurysm • Septic shock • Chronic angina

CLINICAL PEARLS

• Statins are associated with multiple beneficial pleiotropic effects, which improve outcomes in both high-risk and average-risk patients during cardiovascular procedures. • Postoperative statin withdrawal is associated with increased risk of adverse events and death. Statin therapy should not be discontinued prior to open or endovascular procedures and should be resumed postoperatively as soon as possible. • Further randomized clinical studies are needed to define the role and efficacy of the pleiotropic effects of statins in perioperative strategy.

PERIOPERATIVE STROKE Nina Singh-Radcliff, MD Praveen Kalra, MBBS, MD, FCCP

BASICS DESCRIPTION

• Perioperative strokes are predominantly ischemic and embolic (less frequently hemorrhagic). They result in formidable morbidity and unfortunately high mortality. • The majority occur postoperatively (83% vs. 17% intraoperatively) and are usually identified on postoperative Day 1 (45%). • Similar to cardiac disease, the anaesthetist should risk stratify, optimize risk factors, and consider preventive measures in order to reduce incidence and aid in management. EPIDEMIOLOGY Prevalence

• Perioperative stroke ranges from 0.1–5%. • Incidence increases with intraoperative hypotension (1%), the presence of carotid stenosis (3.6%), and cardiac surgery (5%) (1,2). Morbidity/Mortality

Acute mortality: 16–50%. Early mortality may be due to further extension of cerebral infarction with edema and increased ICP. Late mortality may be from aspiration, pneumonia, sepsis, MI, or metabolic derangement. ETIOLOGY/RISK FACTORS

• Patient-related risk factors: Prior stroke or TIA (particularly if within the prior 6 months); advanced age (>70 years old); female gender; long bone fractures; hypertension (particularly poorly controlled); diabetes mellitus; preeclampsia; peripheral vascular disease; carotid disease; arrhythmias; systolic dysfunction (EF <40%); renal disease; hypercoagulability; valvular disease. • Intraoperative (procedure-related) risk factors: Type and nature of surgical procedure; anesthetic choice (GA vs neuraxial vs local); duration of surgery, cardiopulmonary bypass (CPB); aortic cross-clamp time; manipulations of neck or proximal aortic atherosclerotic lesions; arrhythmias; hyperglycemia; hypotension or hypertension; controlled hypotension; urgent surgery; air embolism after endoscopic procedures; intravascular interventions; fat embolism after orthopedic procedures; paradoxical embolism from postoperative deep-vein thrombosis in patients with patent foramen ovale (PFO). • Postoperative risk factors: Heart failure; low ejection fraction; myocardial infarction (MI); arrhythmias (particularly atrial fibrillation); dehydration; blood loss; hyperglycemia; infection. PHYSIOLOGY/PATHOPHYSIOLOGY

• Perioperative strokes are predominantly ischemic and embolic; they result from a combination of patient risk factors, surgical stress and inflammation, as well as anestheticrelated hemodynamic changes. • Atrial fibrillation is a co-morbid disease present in 27.6% of all perioperative strokes. It can cause cardioembolism (particularly when anticoagulants have been held for surgery) or cerebral hypoperfusion (from rapid ventricular rate and hypotension). Perioperative electrolyte abnormalities, sympathetic stimulation, and pulmonary complications may predispose patients to new-onset atrial fibrillation after surgery. • Valvular heart disease and prosthetic valves serve as a nidus for embolus formation, particularly when anticoagulation must be held for surgery. • PFO is present in up to 30% of the general population and provides a direct communication from the right (venous) to the left (arterial) side of the heart. This allows air from IV or other venous catheters to more easily gain access to the cerebral and cardiac arteries (the pulmonary system has some capacity to absorb and exhale air from the venous circulation). • Surgical trauma is associated with tissue injury and disrupted endothelial homeostasis. Microvascular dysfunction, inflammation, and oxidative stress decrease nitric oxide, promote hypercoagulability, and predispose vessels to vasoconstriction, leukocyte adhesion, and thrombosis factors. Furthermore, there is evidence that the fibrinolytic systems are impaired while hemostatic systems are activated postoperatively for up to 21 days: Decreased tissue plasminogen activator (t-PA) and increased activity of plasminogen activator inhibitor type 1 as well as levels of fibrinogen-degradation product, thrombin– antithrombin complex, thrombus precursor protein, and D-dimer. • Carotid endarterectomy: Causes include ischemia during carotid artery clamping, postoperative thrombosis or embolization, and, to a lesser extent, intracerebral hemorrhage. Thrombus and thromboembolization, due to technical error or imperfection at the endarterectomy site, can cause up to 38% of all perioperative strokes. Re-operation and reexploration is often performed to assess for intraluminal thrombi or other causes (1). • Cardiac surgery has multiple factors that increase the incidence of stroke or short- and longterm cognitive changes (executive dysfunction, short-term memory loss, and psychomotor slowing). Causes include intracardiac surgery, surgical trauma, pre-existing vascular changes, temperature, postoperative atrial fibrillation, CPB, and hypoperfusion. Intracardiac surgery introduces gaseous and particulate emboli. Atrial fibrillation occurs in 30–50% of patients postoperatively (peaks on POD 2–4) and has been attributed to electrolyte imbalance and intravascular volume shifts. CPB introduces air, fat, platelet, and fibrin aggregates into the systemic circulation and can lead to stroke. This most frequently occurs during placement and removal of aortic cross-clamps and cannulae (2). • Anesthetic causes stem from hemodynamic changes such as hypotension and hypoxemia; there is some evidence of exacerbating hypercoagulability. Patients with chronic hypertension have a right shift in their cerebral autoregulation curve, making them less capable of handling abrupt drops in BP compared to normotensives. • Dehydration can accelerate thrombus formation due to decreased levels of antithrombin III and increased venous hemostasis.

PREVENTATIVE MEASURES

• Risk stratification includes an assessment of risk factors and optimization of co-morbid

conditions. Those at high risk should be considered for minimization or avoidance of surgery if and when possible. • Carotid disease, particularly symptomatic stenosis, should be evaluated by means of Doppler ultrasound. Patients with >60% stenosis should be evaluated or assessed for correction prior to scheduled surgery; risks of delaying surgery versus the benefits must be weighed. Carotid revascularization prior to, or at the same time as cardiac surgery remains controversial. Opponents state that it exposes patients to the risks of perioperative stroke and MI twice and that the benefits may not exceed the risks. However, the risk of hemodynamically significant, high-grade, asymptomatic carotid stenosis, particularly bilateral stenosis, may exceed that of carotid revascularization. Antiplatelet and aspirin reduces the incidence without increasing the odds of bleeding complications (1). • Recent stroke: Outcome studies suggest delaying surgery for 2–6 weeks; this allows for a stable post-infarction neurologic status to be achieved and for brain vascular reserve to return to normal. However, the urgency of surgery and extent of stroke and co-morbid diseases must be weighed. • Avoid perioperative hyperglycemia, fever, and dehydration. Hyperglycemia should be treated aggressively with insulin. • Infections should be prevented and treated perioperatively (pulmonary, urinary, wound, central lines). High white cell counts correlate with an increased incidence of stroke as well as atrial fibrillation. • Cerebral protection prophylaxis involves measures that reduce oxygen consumption and includes the use of barbiturates or attainment of burst suppression, general anesthesia, and hypothermia. • Neuromonitoring techniques (particularly during CEA or cerebral aneurysm clipping) include functional, flow, and pressure monitors. They help to identify ischemic events. However, they are also indirect and have the potential for false positives and negatives. • Choice of anesthetic: MAC with local infiltration has been associated with a reduced incidence of stroke. Epidural anesthetics have been associated with a reduced incidence of emboli, likely due to the increase in blood flow and reduction in venous stasis in the lower extremities. However, hypotension from sympatholysis should be anticipated, avoided, and aggressively treated. • Cardiac surgery: Consider minimally invasive procedures; minimize duration of CPB, hypotensive episodes, aortic trauma in patients with severe calcification; implement higher MAPs during CPB (especially in patients with carotid disease), de-airing maneuvers of chambers, pulsatile perfusion bypass, hypothermic measures, and alpha-stat pH management. Separately, risk reduction of atrial fibrillation via adequate hydration, maintenance of electrolytes, and possibly prophylaxis with amiodarone, beta-blockers, and statins. Consideration for IV heparin therapy in patients who are high risk (history of CVA or TIA) and develop atrial fibrillation; this should be continued for 30 days after the return of normal sinus rhythm. • Bridging anticoagulation and antiplatelet therapy with medications such as heparin or argatroban may be implemented in order to minimize the period of time where the patient is at risk; consider for high-risk patients. • Resumption of anticoagulants or antiplatelets should be coordinated with the surgical and

primary teams. This involves an assessment of active bleeding (drains, wound sites, stable hemoglobin). • Continuing blood thinners in certain procedures and surgeries such as dental procedures, arthrocentesis, cataract surgery, and endoscopy or colonoscopy with biopsies have minimal risk for major bleeding. Some studies have shown that continuing warfarin for knee or hip replacements with an INR of 1.8–2.1 may be safe and effective. However, blood thinners should be withheld in more invasive procedures. • Statins may reduce the incidence of stroke following major vascular and cardiac surgeries (3% absolute reduction); their role in non-cardiac surgery is not well-defined at this time. The mechanism is believed to be due to pleiotropic effects: Stabilization of atheromatous plaques at risk for rupture, vasodilation by stimulating nitric oxide, reduction of C-reactive protein, and inhibition of thrombosis and platelet aggregation. Although it is clear that patients on chronic statin therapy should be continued perioperatively, the debate exists over initiating statin therapy (which statin, how long, what dose, which patients). • Aspirin therapy is associated with up to 7% absolute reduction in early stroke. • Beta-blockers, although shown to reduce adverse cardiac events and mortality, may increase stroke and mortality perioperatively possibly due to hypotension and bradycardia. However, this is controversial as the key study did not control for BP, timing, type and heart rate parameters.

PREOPERATIVE ASSESSMENT • History of sudden loss of focal brain function or mental status. • Delayed anesthetic awakening should first rule out medication (neuromuscular blocking drugs, narcotics, benzodiazepines, and other sedatives) and metabolic (hypothermia, hypoglycemia, acidosis, alkalosis, hyponatremia, hypercarbia, hypoxia) causes (2). • Non-contrast head CT or MRI • Transesophageal or transthoracic echocardiogram may help detect microemboli and macroemboli, as well as the presence of a PFO. • Neurology consultation.

DIFFERENTIAL DIAGNOSIS

• Delayed anesthetic awakening due to medications or metabolic causes • Delirium • Postoperative toxic metabolic disturbances including hypoglycemia, acute renal failure, drug intoxication, hepatic insufficiency • Seizures • Increased intracranial pressure and edema

TREATMENT • Prevention and prophylactic measures are key, given the poor morbidity and mortality. • Dependent upon cause: In the event of aspiration risk, intubation should be performed. • Thrombolytic therapy for embolic causes may be considered within 48 hours of symptom

onset and after weighing the risks for bleeding. It is contraindicated after major surgery; alternatively, intraarterial administration and endovascular mechanical disruption may be considered. Consult and coordinate with neurology and stroke teams. • Increased intracranial pressure may be treated with ventriculostomy to reduce further injury. • Reduction of cerebral oxygen consumption may be performed via hypothermic measures or barbiturate coma or burst suppression. • Normoglycemia should be maintained. Hyperglycemia has been associated with worsened outcomes as well as increased atrial fibrillation. • BP management remains controversial. Most consensus guidelines recommend that BP NOT be treated acutely in patients with ischemic stroke unless SBP >220 mm Hg or DBP >110 mm Hg or the patient has active CAD, heart failure, or aortic dissection. In addition to arterial line BP monitoring, potential IV choices include labetalol, nicardipine, nitroglycerin, and nitroprusside. • Antihypertensive medications may be restarted approximately 24 hours after stroke in patients with preexisting hypertension who are neurologically stable. • Anticipate and prevent medical complications of stroke. Common conditions associated with stroke are MI, heart failure, dysphasia, aspiration, pneumonia, urinary tract infection, DVT, PE, dehydration, malnutrition, and pressure sores.

FOLLOW-UP • Neurology consult • Physical and occupational therapy

CLOSED CLAIMS DATA

• Stroke comprises 3% of all claims (N = 6446)

REFERENCES

1. alm EA, Tuhrim S, Wang JJ, et al. Risk factors for perioperative death and stroke after carotid endarterectomy: Results of the New York carotid artery surgery study. Stroke. 2009;40(1):221–229. 2. ouglas JM, Spaniol SE. A multimodal approach to the prevention of postoperative stroke in patients undergoing coronary artery bypass surgery. Am J Surg. 2009;197(5):587–590. 3. Selim M. Current concepts perioperative stroke. NEJM. 2007;356:706–713 4. anders RD, Grocott HP. Perioperative stroke: Time to redefine the impact of age? Stroke. 2012;43:3–5. 5. ashour G, Shanks A, Kheterpal S. Perioperative stroke and associated mortality after noncardiac, nonneurologic surgery. Anesthesiology. 2011;114(6):1289–1296. 6. arik S, Cohen JR. Perioperative stroke after general surgical procedures. NY State J Med. 1993;93(3):162–165. 7. cDonagh D, Mathew J. Perioperative stroke: Where do we go from here? Anesthesiology.

2011;114(6):1263–1264. 8. ateman B, Schumacher H, Wang S, et al. Perioperative acute ischemic stroke in noncardiac and nonvascular surgery: Incidence, risk factors, and outcomes. Anesthesiology. 2009;110(2):231–238.

ADDITIONAL READING

• American Society of Anesthesiologists Closed Claims Study • Poldermans D, Schouten O, van Lier, et al. Perioperative stroke and beta-blockade. Anesthesiology. 2009;111(5):940–945. See Also (Topic, Algorithm, Electronic Media Element)

• Atrial fibrillation • Carotid endarterectomy • Cardiopulmonary bypass • Electroencephalogram (EEG)

CODES ICD9 997.02 Iatrogenic cerebrovascular infarction or hemorrhage ICD10 I97.811 Intraoperative cerebrovascular infarction during oth surgery

CLINICAL PEARLS

• Perioperative stroke is a grave complication that increases with certain patient, surgical, and anesthetic factors. • The majority of perioperative strokes are secondary to thromboembolic phenomenon.

PERIPHERAL VASCULAR DISEASE Eric W. Nelson, MD

BASICS DESCRIPTION

• Organic peripheral vascular disease (PVD) is atherosclerosis of blood vessels outside of the heart and brain. – It results from hardening and narrowing of blood vessels and causes insufficient tissue perfusion, similar to coronary or carotid artery disease. – It is a systemic disease that affects many circulatory networks including the kidneys, extremities, and stomach. • Patients with PVD frequently present for vascular as well as non-related procedures (1,2). – Peripheral vascular surgery is classified as a “high-risk” surgical procedure by the American Heart Association Perioperative Guidelines. – Even in non-vascular procedures, patients present with significant comorbidities that can result in “high” or “intermediate” patient risk stratification. EPIDEMIOLOGY Prevalence

• 12–14% of individuals in the general population (3). • 20% of individuals over the age of 70 years (3). • 1 in 3 diabetics over the age of 50 years (3). • Endovascular procedures are increasing in frequency; approximately 1,300 endovascular abdominal aortic aneurysm (AAA) repairs are performed each year in the US.

Morbidity

50% of affected patients had a major event or surgery in a 6-year time span. Mortality

33.2% death rate over 5 years ETIOLOGY/RISK FACTORS • Diabetes (2,3) • Hypercholesterolemia • Coronary artery disease • Hypertension • Renal failure • Smoking

PHYSIOLOGY/PATHOPHYSIOLOGY

• PVD can be classified as either organic (the result of atherosclerosis) or functional

(thrombosis, emboli, acute trauma, vasculitis, autoimmune disease). The focus of this chapter is organic PVD (3). • Atherosclerosis can be described as a ubiquitous process of chronic low-grade inflammation and plaque formation with the possibility of superimposed acute thrombotic events. • PVD affects the venous and arterial systems and impairs perfusion. This can result in chronic distal ischemia and increases the potential for acute complete occlusion and infarction.

ANESTHETIC GOALS/GUIDING PRINCIPLES

Myocardial dysfunction is the most important cause of morbidity in patients with PVD; therefore, cardioprotective strategies should not only be maintained during anesthesia, but also perioperatively.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Intermittent claudication is typically an early symptom. • Pain at rest is a more worrisome symptom as it typically signifies ischemia in the affected extremity. • Patients also typically notice skin changes on the affected extremity.

History

• Duration and progression of PVD, activity level, pain. • A complete history of the patient’s PVD must be supplemented by a thorough investigation of other vascular diseases (cardiovascular, cerebrovascular, renovascular) to help determine the best type of anesthetic, monitoring, and if further workup is necessary.

Signs/Physical Exam

• 5 P’s of PVD: Pain, pallor, paresthesia, paralysis, pulselessness • Auscultate for bruits and palpate for thrills • Skin examination: Atrophic and shiny, alopecia, dry, scaly, erythema, brittle nails

MEDICATIONS

• Cardioprotective drugs: Beta-blockers, statins, aspirin, ACE inhibitors • Cilostazol and pentoxifylline help to decrease claudication in patients with PVD but have not been found to decrease mortality. • Oral hypoglycemics and insulin are commonly seen; patients should hold long-acting oral drugs on the morning of surgery to avoid perioperative hypoglycemia. Metformin is commonly held perioperatively due to its potential for fatal metabolic acidosis. • Anticoagulation: Potent platelet inhibitors, heparin infusions, or thrombolytic therapy may need to be started or continued perioperatively; this decision should be discussed with the surgeon and the cardiologist.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes to assess renal function • CBC to assess for anemia, quantitative platelet abnormalities • ECG to check for dysrhythmias, ischemia, infarction • A cardiac stress test may be indicated to assess function and the potential for ischemia. If the patient has good exercise tolerance, >4 METS, cardiac workup is typically not necessary (however, their PVD may affect activity levels independent of coronary disease and preclude the ability to assess this). • Pulmonary function testing may be indicated in patients with lung dysfunction, particularly in surgical procedures with the potential for postoperative impairment (thoracic, upper abdominal procedures). CONCOMITANT ORGAN DYSFUNCTION

• Coronary artery disease • Chronic obstructive pulmonary disease • Cerebrovascular disease • Renal dysfunction

CIRCUMSTANCES TO DELAY/CONDITIONS

• Non-vascular procedures: If there is worsening of claudication or pain at rest, this may signal progression of disease and the need to address/treat a priori. • Absence of cardiac workup or management in patients with coronary disease or with myocardium that appears at risk for ischemia CLASSIFICATIONS

Fontaine stages for ischemia • Mild claudication • Intermittent claudication (pain with walking about 150 m) • Rest pain • Gangrene

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytics can allay increases in BP and heart rate. • Beta-blockers should be continued and titrated to goal heart rates (3). • Supplemental oxygen may be appropriate. • Blood sugar control with IV or SQ insulin as appropriate (3). • Bronchodilators and steroids may be considered in patients with pulmonary disease. • Gastric medications such as antacids, prokinetics, and acid reducers should be considered in patients with gastroparesis or delayed gastric emptying.

Special Concerns for Informed Consent

• If the patient has a history of neurovascular disease, and is deemed not competent, informed

consent may have to be obtained from a power of attorney. • Discuss smoking cessation

INTRAOPERATIVE CARE Choice of Anesthesia

• Outcome studies on anesthetic choice for PVD procedures and patients have yielded varying results and conclusions. At this time, recommendations or guidelines applicable to all patients, procedures, and situations do not exist. Rather, risks versus benefits and practicality need to be weighed. • Epidural and spinal – Benefits include the ability to block the endocrine stress response seen with surgery; avoids the need for airway manipulation and controlled ventilation; reduces the potential for blood loss, hemodynamic swings associated with general anesthesia and hypercoagulability; increases blood flow and perfusion to lower extremities and decreases time to ambulation; diminishes need for systematic opioids and their side effects (respiratory complications). – Drawbacks include risks associated with neuraxial techniques (infections, hematomas, difficult placement, high spinals, inadvertent intravascular injection) and contraindications with common anticoagulants. • Peripheral nerve blocks – Benefits include the ability to block the endocrine stress response seen with surgery as well as avoid the need for airway manipulation, controlled ventilation, and systemic opioids. – Drawbacks include failed or incomplete surgical blocks, local anesthetic systemic toxicity, complications of sedation (hypoxia, hypercarbia), and concerns with anticoagulants (brachial plexus blocks in the thorax). • General anesthesia – Benefits include the potential for a still surgical field, controlled ventilation, and patient preference to not be awake. • MAC with local anesthetic infiltration should be considered when appropriate as it avoids many of the drawbacks seen with the above mentioned techniques

Monitors

• Standard ASA monitors • ECG and ST segment monitoring will help to detect perioperative myocardial ischemia in this high-risk patient population. • Arterial line placement should be considered in patients with concurrent coronary artery disease, decreased left ventricular function, or for procedures with the potential for large swings in BP and/or require beat-to-beat BP monitoring. Consider pre-induction placement. PVD may make line placement difficult.

Induction/Airway Management

Slow and controlled to ensure steady hemodynamics and organ perfusion as well as provide an adequate depth of anesthesia. Heart rate, EKG, and arterial line/NIBP should be carefully monitored and abnormalities treated to optimize myocardial oxygen supply and perfusion.

Maintenance

• The myocardial oxygen supply and demand ratio needs to be optimized. It may be necessary to place more invasive monitors as needed intraoperatively. • In patients with chronic hypertension, the cerebral perfusion pressure curve may be shifted to the right. A good rule of thumb is to maintain BP within 20% of the patient’s baseline. • Normothermia should be maintained to avoid shivering and increased myocardial oxygen consumption. • Glycemic control should be considered in long or brittle diabetics.

Extubation/Emergence

• Avoid or treat shifts in BP and heart rate. • Consider “deep” extubation in patients with COPD to avoid bronchospasm.

FOLLOW-UP BED ACUITY

• Patients should typically be monitored on telemetry as most have CAD. • Monitoring of pulses and color of the affected extremity is useful in determining worsening of disease.

MEDICATIONS/LAB STUDIES/CONSULTS

• Restart cardioprotective medications as soon as appropriate. Discontinuation of statin therapy has been affiliated with increased cardiac morbidity and mortality (4). • Tight glycemic control can improve wound healing and reduce the incidence of infection • Consider BMP and replace electrolytes; CBC if there was blood loss during the surgery. Transfusion may be necessary to maintain adequate oxygen carrying capacity in the blood (however, it carries intrinsic risks).

COMPLICATIONS

• MI is the major source of morbidity in this population. • Extremity ischemia may occur. • Worsening renal disease • Cerebrovascular accidents

REFERENCES

1. Fleisher LA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Anesth Analg. 2008;106(3):685–712. 2. Kheterpal S, O’Reilly M, Englesbe MJ, et al. Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery. Anesthesiology. 2009; 110:58–66. 3. Shammas NW. Epidemiology, classification, and modifiable risk factors of peripheral

arterial disease. Vasc Health Risk Manag. 2007;3(2):229–234. 4. Schouten O, Hoeks SE, Welten GM, et al. Effect of statin withdrawal on frequency of cardiac events after vascular surgery. Am J Cardiol. 2007; 100(2):316–320. 5. Hallet JW. Peripheral Arterial Disease. The Merck Manuals Online Medical Library. 2008. • www.americanheart.org See Also (Topic, Algorithm, Electronic Media Element) • Coronary artery disease • Cerebrovascular disease • Carotid endarterectomy • Lower extremity bypass

CODES ICD9 443.9 Peripheral vascular disease unspecified ICD10 I73.9 Peripheral vascular disease, unspecified

CLINICAL PEARLS

• Peripheral vascular surgery is considered a high-risk surgical procedure. Patients presenting for peripheral vascular surgery often do so after failed medical or endovascular management. • In addition, patients often have intermediate or high-risk cardiac comorbidities that increase the possibility for perioperative morbidity or mortality. Common comorbidities include hypertension, coronary artery disease, cerebrovascular disease, diabetes mellitus, and pulmonary disease from smoking. • It is important to obtain a detailed cardiac history to decrease the risk of perioperative MI as much as possible.

PH MEASUREMENTS Sara Miller, MD Priti G. Dalal, MD, FRCA

BASICS DESCRIPTION

pH measurements are most commonly measured by blood gas analyzers. They are comprised of a: • pH sensor: Contains a measuring and reference electrode. • PCO2 electrode: A pH sensitive glass probe that is surrounded by a bicarbonate solution and is enclosed by a CO2 permeable membrane.

• PO2 electrode: A platinum probe bathed in an electrolyte solution and separated from the blood sample by an O2 permeable membrane (1)[A].

PHYSIOLOGY PRINCIPLES • pH is a measure of the hydrogen ion (H+) concentration in a liquid. pH is defined as the negative logarithm to the base 10 of H+. For example, if H+ equals 0.000001, then pH is equal to the negative log10[0.000001], or 6.0. • Modern blood gas analyzers directly measure: – pH: Sensing (or measuring) electrodes produce an electrical signal or potential (voltage) that is directly related to the [H+]. Reference electrodes produce a stable potential by which the potential difference is measured and converted into a pH value. – CO2 tension: CO2 is relatively soluble in blood, and exists in other forms: HCO3-, CO2, H2CO3 (CO2 + H2O←→H2CO3 ←→H+ + HCO3-). It is attached to hemoglobin as carbaminohemo- globin. These dissolved and bound forms exist in equilibrium with CO2

in its gas form, but do not exert partial pressure and are not included in the PaCO2

measurement. – Arterial oxygen tension: O2 is poorly soluble in blood; the solubility coefficient is 0.003.

Most of the O2 is carried in blood attached to hemoglobin. Dissolve and bound forms exist in equilibrium with O2 in its gas form, but do not exert partial pressure and are not included in the PaO2 measurement.

– Current equipment may also have the capability of measuring hemoglobin, electrolytes, glucose, and lactate. – Samples are warmed to 37%C prior to measurement. • Modern blood gas analyzers calculate: – Arterial oxyhemoglobin saturation – Base excess: A reflection of the amount of strong acid necessary to bring the pH to 7.4

– Bicarbonate concentration. This value is derived from the pH and PCO2 measured values.

• Factors that can affect the accuracy of pH measurements: – Gas solubility: Changes in temperature affect the kinetic energy of O2 and CO2 and

consequently the solubility of gases in blood (partial pressures). For example, decreased temperature will consequently decrease the kinetic energy of O2 and CO2; this increases their solubility and decreases their partial pressures (less in gas form). In addition, there is an increase in O2 and CO2 binding affinity to hemoglobin which further decreases the

amount of oxygen and carbon dioxide in its gas form. – Water dissociation constant (pKw): Changes in temperature affect water’s self-ionization (proton from one water molecule is transferred to another to form hydronium and hydroxide ions). H2O + H2O ←→ H3O+ + OH−. Water is the primary source of

hydrogen ions. Thus, decreased temperature will decrease [H+] and hence increase the pH (alkalosis). – Electroneutrality: Maintained due to the compensatory pK adjustment of histidine’s imidazole moieties (alpha residues) that parallel pKw. Imidazole retains its buffering capacity at all temperatures. – Storage time: A sample that is stored longer than 20 minutes before analyzing it can artificially change measured and calculated values, due to environmental cooling and cellular metabolism. Blood samples are warmer than the ambient temperature, and cooling can cause increased oxygen solubility, thereby reducing PO2. In addition, as cellular metabolism ensues, PCO2 increases and PO2 and pH decrease.

– Number of cells in the sample: Increases in the WBC, platelet, or hemoglobin levels result in increased metabolism. To reduce this effect, samples are normally placed on ice after they are obtained to maintain their stability and the addition of sodium fluoride or cyanide can reduce cellular oxygen consumption. • Cardiopulmonary bypass (CPB) management presents a unique dilemma due to the implementation of significant hypothermia. To that extent, two techniques of management are utilized. Controversy exists regarding the most optimal methods. Blood gas samples need to be warmed to 37°C prior to measurement. Whether these values are then inserted into a table or nomogram in order to temperature “correct” for partial pressures and pH to the patient’s actual temperature is what is referred to as alpha stat and pH stat measurements. – pH stat utilizes a nomogram or table to adjust to the patient’s current hypothermic temperature. The readings, therefore, will reflect in vivo partial pressures and pH (reduced partial pressures, increased pH). Management based upon these values will result in the addition of CO2 to the CPB pump in order to increase PaCO2 and reduce pH.

– Alpha stat pH management does not utilize a nomogram or table to adjust to the patient’s hypothermic temperature. This is referred to as an “uncorrected” temperature system. Thus, although in vivo partial pressures may be lower and pH higher than measured values, management using this technique focuses on “total” content and does not add CO2

to the CPB pump or affect electroneutrality. • Transcutaneous blood gas analysis is a continuous, non-invasive method to monitor blood

gas levels. The device induces hyperperfusion by local heating and PtcO2 and PtCO2 are

measured electrochemically; these values are used to estimate PaO2 and PaCO2. This technique may be inaccurate in hypoperfused states and when vasoactive drugs are used.

ANATOMY

• pH measurements can be drawn commonly from the radial artery located on the distal lateral wrist or from the femoral artery which is lateral to the femoral vein and medial to the femoral nerve in the crease of the groin. • Venous pH can be measured from any of the veins, commonly from the antecubital vein. • “Arterialized” samples may be considered from an extremity vein that has minimal tissue extraction (cold extremity).

PHYSIOLOGY/PATHOPHYSIOLOGY

CPB: • pH stat management usually requires adding CO2 to the oxygenated gas inflow. This

increases total blood CO2 content and increases cerebral blood flow (results in cerebral

autoregulation uncoupling). This “luxuriant” flow may result in an increased embolic load (including air), thus potentially increasing the risk of cerebral injury (2)[B]. In ischemic stroke, pH stat management has been shown to imply better cerebral blood flow to injured brain, but it may be dangerous by elevating intracranial pressure in subacute stages (3)[B]. • Alpha stat management preserves cerebral autoregulation. There is no CO2 added to the oxygenator; thus total CO2 content stays constant. Normally, cerebral blood vessels are able

to adjust the flow of blood by vasoconstriction when arterial BP is raised and vasodilation when arterial BP is lowered; thus if the PaCO2 doubles, the CBF doubles. Since alpha stat

management maintains CO2 at normal levels, cerebral autoregulation in response to BP remains intact. As a result, it may have less adverse effects on enzyme function and cerebral autoregulation, and is more commonly utilized during CPB.

PERIOPERATIVE RELEVANCE

• Arterial blood gas measurements are useful perioperatively and on the floor when acid–base or oxygenation abnormalities are suspected. – Preoperatively, baseline values can be attained to assess a patient’s normal respiratory status. Abnormalities can aid with risk stratification, the need for preoperative optimization, as well as ventilatory settings, invasive monitors, and bed acuity. – Intraoperatively, arterial blood gas measurements are used to identify respiratory and metabolic derangements. Hypoxia and alveolar–arterial oxygen gradients can aid with discerning between ventilation/perfusion mismatching, shunting or diffusion barriers. Extubation criteria are often based upon clinical signs and examination; however, in some patients, arterial blood gas measures are useful in identifying patients who may fail extubation. – Intensive care unit: Intubated patients are carefully assessed for the return of adequate mechanical functions as well as PO2 and PCO2 levels during spontaneous ventilation.

• pH stat versus alpha stat approaches during CPB: Patients managed by the pH stat approach are considered hypercarbic and have a lower pH (respiratory acidosis). Patients managed by the alpha stat approach are considered hypocarbic and have an increased pH (respiratory alkalosis). The two techniques may have different cerebral and cardiac outcomes, and controversy exists as to which approach yields a better patient outcome Comp Please change this to a single sentence. – Adults: Several studies have shown that during moderate hypothermia, alpha stat management produces better neurologic outcomes, and is thus more widely used. – Pediatrics: Several studies have shown that pH stat management produces better neurologic outcomes secondary to decreased oxygen consumption, more homogenous brain cooling, and better cerebral metabolic recovery. Data also shows that pH stat management results in better outcomes with shorter ventilation times and shorter intensive care unit stays after pediatric cardiac surgery (4)[B]. Thus, pH stat is more commonly used; it may also be combined with alpha stat (pH stat used during cooling and alpha stat used during rewarming) (5)[B].

EQUATIONS

pH = 6.1 + log [HCO3-]/ 0.03 × PaCO2 GRAPHS/FIGURES See Table

REFERENCE

1. everinghaus JW. First electrodes for blood PO2 and PCO2 determination. J Appl Physiol. 2004;97:1599–1600. 2. Hoover LR, Dinavahi R. Jugular venous oxygenation during hypothermic cardiopulmonary bypass in patients at risk for abnormal cerebral autoregulation. Influence of alpha stat versus pH-stat blood gas management. Anesthesia and Analgesia. 2009;108:1389–1292. 3. Kollmar R, Georgiadus D, Schwab S. Alpha stat vs. pH stat guided ventilation in patients with large ischemic stroke treated by hypothermia. Neurocritical Care. 2009;2:173–180. 4. Griffin DA. Blood gas strategies and management during pediatric cardiopulmonary bypass. ASAIO Journal. 2005;5:657–658. 5. Groom RC, Froebe S, Martin J, et al. Update on pediatric perfusion practice in North America: 2005 survey. J Extra Corpor Technol. 2005;37:343–350. 6. Yao F, Malhotra V, Fontes M. Yao and Artusio’s anesthesiology: Problem oriented patient management, 2007. See Also (Topic, Algorithm, Electronic Media Element) • Extubation and intubation criteria • Metabolic acidosis • Anaerobic metabolism • Respiratory alkalosis • Respiratory acidosis

• Cardiopulmonary bypass

CLINICAL PEARLS

• pH measurements aid with diagnosing cardiorespiratory system function and derangements as well as managing acid–base disorders. • Arterial blood gas measurements may have flaws due to cooling of the sample and cellular metabolism that can affect accuracy. • pH stat: • Is temperature corrected • Aims to keep PaCO2 normal • Requires adding CO2 to inspired gases • Increases cerebral blood flow • Uncouples cerebral autoregulation. • Alpha stat: • Is temperature uncorrected • Does not add CO2 to inspired gases

• Maintains electrochemical neutrality • Preserves cerebral autoregulation • More commonly used in adult CPB.

PHEOCHROMOCYTOMA Joe C. Hong, MD

BASICS DESCRIPTION

• Pheochromocytoma is a rare endocrine disorder characterized by catecholamine-secreting tumors of chromaffin tissue. The hallmark of pheochromocytoma is the excess production of catecholamines. • 10% of pheochromocytomas are extra-adrenal; they can occur wherever chromaffin tissue is located. These sites include the celiac, mesenteric, renal, hypogastric, testicular, and paravertebral sympathetic nerve plexus. EPIDEMIOLOGY Prevalence

In the US: ∼800 new cases/year Prevalence

• ∼1:5,000 patients with hypertension have pheochromocytoma. • Prevalence equal in men and women.

Morbidity/Mortality

• Patients with pheochromocytoma are at increased risk of multisystem morbidity and mortality, particularly of the cardiovascular system. Comorbidities are the result of high catecholamine levels on the end organs. • Intraoperative diagnosis of a previously unknown pheochromocytoma is associated with morbidity and mortality approaching 50% (primarily from myocardial infarctions or cerebrovascular accidents) (1). • Preoperative diagnosis with appropriate medical and anesthetic management significantly decreases perioperative mortality and morbidity. ETIOLOGY/RISK FACTORS

Positive family history of pheochromocytoma, multiple endocrine neoplasia (MEN) syndrome, or von Hippel–Lindau disease. PHYSIOLOGY/PATHOPHYSIOLOGY

• The vast majority of pheochromocytomas arise spontaneously; however, some are associated with familial syndromes such as simple familial pheochromocytoma, MEN types IIa and IIb, neurofibromatosis, tuberous sclerosis, von Hippel–Lindau disease, and Sturge–Weber syndrome. • Rule of 10: Approximately 10% familial, 10% bilateral, 10% extra-adrenal, and 10% malignant.

• Pheochromocytomas are capable of manufacturing, storing, and secreting catecholamines (norepinephrine, epinephrine, and dopamine). The vast majority (90%) secrete predominately norepinephrine (2).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Prior to surgery, patients must be adequately alpha-blocked followed by beta-blocked, volume resuscitated, and concomitant organ dysfunctions identified and optimized prior to surgery (3). • Careful intraoperative communication between the surgeon and the anaesthetist must take place to help anticipate periods of hemodynamic fluctuation.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Manifestations of supraphysiologic activity of catecholamines. Headaches, palpitations, and diaphoresis are the most common symptoms. • Other symptoms include anxiety, flushing, flank pain, abdominal pain, dizziness, syncope, nausea, vomiting, weight loss, and constipation.

History

• In patients with undiagnosed pheochromocytoma, clinical suspicion is warranted when the patient exhibits a history of difficult to control hypertension despite multiple drug therapy or paroxysmal spells of sudden increases in BP, headaches, diaphoresis, palpitation, and pallor. • In patients with known diagnosis, a careful review of a BP diary, antihypertensive regimen, duration of therapy, and timing of last dose will help establish adequacy of alpha-blockade. • History taking should also identify other signs of adequate alpha-blockade such as nasal congestion and orthostasis. • A focused, relevant review of systems should include neurologic, cardiovascular, hematologic, gastrointestinal, metabolic, pulmonary, and musculoskeletal systems.

Signs/Physical Exam

• Manifestations of supraphysiologic activity of catecholamines. Hypertension is the most common sign and can be either sustained or paroxysmal. • Other signs and examination findings include fever, tachycardia, orthostatic hypotension, and palpable flank mass.

MEDICATIONS

• Preoperative alpha-blockade is vital in controlling BP and reversing catecholamine-induced vasoconstriction and hypovolemia. • Oral phenoxybenzamine, a non-competitive alpha-1 and alpha-2 antagonist, is the drug of choice for alpha-blockade. It should be started and titrated upward, ideally, several weeks prior to surgery (4). • Oral prazosin and doxazosin are alpha-1 antagonists with fast onset and short half-lives making them easier to titrate. Competitive antagonism puts them at a disadvantage as they

can be overcome by a large catecholamine surge. • Phentolamine is an intravenous competitive alpha-1 and alpha-2 antagonist. The competitive nature of antagonism also means that it can be overcome by a large catecholamine surge. • Beta-blockade should be used only after achieving adequate alpha-blockade (if not, can cause a relatively unopposed alpha-adrenergic tone, resulting in CHF). Beta-blockade is important for the control of tachycardia, arrhythmias, and myocardial ischemia. Metoprolol is the agent of choice after adequate alpha-blockade. Labetalol with a beta:alpha ratio of 3:1 is a good alternative.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Elevated free catecholamine or catecholamine metabolites in a 24-hour urinary sample has the highest sensitivity for making a laboratory diagnosis. • Imaging studies utilizing CT and MRI offer accurate and consistent identification of adrenal pheochromocytomas. • 131I-meta-iodobenzyl guanidine (MIBG) scan is useful in detecting recurrent tumors, metastases, and extra-adrenal tumors. • Hgb in unblocked patients will show polycythemia due to hemoconcentration. Adequate alpha-blockade will result in blood volume re-expansion and a decrease of Hgb back to normal values. • Chemistry panel should be ordered to assess hyperglycemia and renal function. • EKG should be examined for evidence of arrhythmias, ischemia, and left ventricular hypertrophy. • Chest x-ray should be examined for evidence of CHF. • Echocardiogram to assess for cardiomyopathy should be considered if there is a decrease in exercise tolerance.

CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular: Increased risk of arrhythmias, particularly ventricular tachycardia and fibrillation; dilated and hypertrophic cardiomyopathy in chronic high catecholamine states; and congestive heart failure, myocarditis, and myocardial infarction. • Pulmonary: Cardiogenic pulmonary edema from dilated cardiomyopathy as well as noncardiogenic pulmonary edema. • Gastrointestinal: High catecholamine state may decrease peristalsis leading to ileus and obstipation. • Renal: Renal artery stenosis from mass effect and renal infarction from hypertensive crisis leading to acute renal failure. • Hematologic: Polycythemia from intravascular volume depletion secondary to high systemic vascular resistance. • Metabolic: Glucose intolerance leading to diabetes. Lactic acidosis.

CIRCUMSTANCES TO DELAY/CONDITIONS

Recently diagnosed pheochromocytoma without adequate alpha-blockade.

TREATMENT PREOPERATIVE PREPARATION Premedications

Benzodiazepine and opioids are helpful for awake arterial line placement. INTRAOPERATIVE CARE Choice of Anesthesia

• The vast majority of adrenalectomies for resection of pheochromocytoma are performed via the laparoscopic approach. Deep general endotracheal anesthesia is the technique of choice. • Neuraxial anesthesia to provide analgesia for incisional pain should be considered when open adrenalectomy is planned. It does not, however, prevent catecholamine surges; and hypotension after ligation of venous drainage may be more difficult to treat with sympatholysis. Monitors

• Standard ASA monitors • Arterial line • Central venous catheter; pulmonary artery catheter if evidence of catecholamine-induced cardiomyopathy or CHF • Urinary catheter

Induction/Airway Management

• Induction should only proceed after arterial BP monitoring is established and emergency drugs to treat acute hypertension and tachycardia are immediately available. • Propofol can be used safely for induction. Patients need to be deeply anesthetized prior to laryngoscopy and intubation. Drugs that increase sympathetic activity such as ketamine should be avoided. • Succinylcholine should be used with caution due to the theoretical concern that fasciculations will increase intraabdominal pressure leading to tumor compression and release of catecholamines. • Nondepolarizing muscle relaxants (mivacurium, atracurium) that liberate histamine, which can stimulate catecholamine release, should be avoided. Pancuronium, with sympathomimetic activity, should also be avoided. Maintenance

• Patients should be maintained at a deep level of general anesthesia. Opioids and volatile anesthetics that do not sensitize the heart to catecholamines should be used. • Anticipate marked increases in BP and heart rate during the establishment of pneumoperitoneum and tumor manipulation. Mechanical compressive forces during these two critical stages of surgery may cause release of catecholamines. • Nitroprusside infusion via a central venous catheter provides a quick on, quick off method of BP control that is easy to titrate. Other medications used successfully to temporize surges in catecholamine include nitroglycerine, phentolamine, nicardipine, and esmolol.

• Anticipate marked decrease in BP and heart rate during ligation of the tumor’s venous drainage. The sudden removal of the catecholamine source can precipitate hypotension in a well alpha-blocked patient. – Intravascular volume loading prior to ligation of venous drainage can temporize the hypotensive effect of acute catecholamine withdrawal. – Vasopressin infusion via a central venous catheter provides an effective method to treat hypotension as it does not rely on the availability of alpha-adrenergic receptors (which may still exhibit a significant degree of antagonism from preoperative alpha-blockade). – Phenylephrine, norepinephrine, and epinephrine can be used to treat hypotension. However, a larger than anticipated dose may be necessary due to preoperative alphablockade. • Glucose should be checked at regular intervals after ligation; the sudden withdrawal of catecholamines may cause acute hypoglycemia.

Extubation/Emergence

General extubation criterion can be used.

FOLLOW-UP BED ACUITY

Patients with persistent labile BP requiring a postoperative infusion of vasoactive medications should be monitored in the ICU. COMPLICATIONS

• The majority of intraoperative complications are related to catecholamine-induced extremes of BP and heart rate. These may manifest as stroke, cerebral hemorrhage, myocardial ischemia and infarct, other major end-organ damage, and death. • Common postoperative complications include hypotension, hypertension, and hypoglycemia. – Hypotension is most common and is likely due to a combination of residual preoperative alpha-blockade, insufficient volume resuscitation, adrenoreceptor down-regulation, and lack of catecholamine output from the contralateral adrenal gland that had been chronically suppressed. – Most common cause of residual hypertension is due to elevated catecholamine stores in adrenergic nerve endings. This may persist for up to 1 week after resection. Other causes of residual hypertension include volume overload, inadvertent ligation of a renal artery, or presence of residual tumor.

REFERENCES

1. Pacak K. Preoperative management of the pheochromocytoma patient. J Clin Endocrinol Metab. 2007;92(11):4069–4079. 2. Connery LE, Coursin DB. Assessment and therapy of selected endocrine disorders. Anesthesiol Clin North America. 2004;22(1):93–123.

3. Kinney MA, Warner ME, vanHeerden JA, et al. Perianesthetic risks and outcomes of pheochromocytoma and paraganglioma resection. Anesth Analg. 2000;91(5):1118–1123. 4. Witteles RM, Kaplan EL, Roizen MF. Safe and cost-effective preoperative preparation of patients with pheochromocytoma. Anesth Analg. 2000;91(2):302–304.

ADDITIONAL READING

• Kinney MA, Narr BJ, Warner MA. Perioperative management of pheochromocytoma. J Cardiothorac Vasc Anesth. 2002;16(3):359–369. • Prys-Roberts C. Phaeochromocytoma – recent progress in its management. Br J Anaesth. 2000; 85(1):44–57.

See Also (Topic, Algorithm, Electronic Media Element) • Adrenalectomy • Laparoscopy

CODES ICD9 227.0 Benign neoplasm of adrenal gland ICD10 • D35.00 Benign neoplasm of unspecified adrenal gland • D35.01 Benign neoplasm of right adrenal gland • D35.02 Benign neoplasm of left adrenal gland

CLINICAL PEARLS

• Pheochromocytoma may present with paroxysmal spells known as the “5 P’s” – Pressure: Sudden increase in BP – Pain: Headache, abdominal and flank pain – Perspiration – Palpitation – Pallor • Patients with pheochromocytoma must be adequately alpha-blockade followed by betablocked (if tachycardic), volume resuscitated, and concomitant organ dysfunctions identified and optimized prior to surgery. Phenoxybenzamine is the alpha-blocker of choice as it mediates antagonism in a non-competitive fashion. • Signs of adequate alpha-blockade include re-expansion of intravascular volume as measured by the normalization of Hgb concentration, normalization of BP, and nasal congestion. • Intraoperative hemodynamic fluctuations are most prominent during induction/intubation, establishment of pneumoperitoneum, tumor manipulation, and ligation of the tumor’s venous drainage. • Arterial line is needed to monitor for hemodynamic fluctuations. Central venous catheter is useful for assessing volume status and for vasoactive drug infusions. Pulmonary artery

catheter is utilized if there is any evidence of catecholamine-induced cardiomyopathy or CHF. • Intraoperative hypertension is best managed with titration of nitroprusside and esmolol. • Intraoperative hypotension occurs after ligation of venous drainage and is best managed by intravascular volume resuscitation and temporized by an infusion of vasopressin. • Common postoperative complications include hypotension, hypertension, and hypoglycemia.

PHOSPHATE

Ravi S. Tripathi, MD Erik E. Abel, PharmD, BCPS

BASICS DESCRIPTION

• Phosphate is an abundant intracellular anion and required for cell membrane structure, cellular energy, cell transport, and oxygen release from hemoglobin. • Normally, phosphate is maintained at 3–4.5 mg/dL in adults and 4–5 mg/dL in children. • Abnormalities of phosphate homeostasis are seen in many common perioperative conditions such as malnutrition, alcoholism, sepsis, trauma, hyperparathyroidism, patients with metastases, major surgery, diabetic ketoacidosis, refeeding syndrome, and pathophysiologic states associated with high serum catecholamine levels. PHYSIOLOGY PRINCIPLES

• Phosphate is required for many key cellular functions: – Adenosine triphosphate (ATP) and creatinine phosphate as an energy store via highenergy phosphate bonds – DNA and RNA in genetic translation – 2,3-diphosphoglycerate (2,3-DPG) as a key component in oxygen transport and release of oxygen to tissues – Cellular metabolism with uptake of phosphate increased by ingestion of glucose, fructose, insulin levels, beta-adrenergic stimulation and anabolism – Phospholipids and cell membrane structure – Hydroxyapatite in bone makes up 90% of total body phosphate (the remaining 10% is intracellular and <1% is extracellular) – Inorganic phosphate provides an acid–base buffering system • Absorption: Phosphate is normally ingested in excess of daily requirement – It is absorbed passively in the small intestine (duodenum and jejunum); however, it becomes an active sodium-dependent transport process in hypophosphatemia. – Calcium, magnesium, aluminum and other cations can decrease absorption by binding/chelating phosphate. – Absorption is also regulated by 1,25-dihydroxyvitamin D3. – Decreased phosphate absorption leads to the pathology of hypophosphatemia in postoperative and/or physiologically stressed patients • Production: When the body requires extra calcium, bone (hydroxyapatite) is broken down and phosphate (in addition to calcium) is liberated. • Excretion: Excess phosphate is excreted via the kidneys and the gastrointestinal system. – In the glomerulus, phosphate is filtered freely with a glomerular concentration similar to plasma. – In co-transport with sodium, phosphate is reabsorbed in the proximal tubule. This co-

transport is regulated by plasma levels and the parathyroid hormone (PTH). PTH normally inhibits phosphate reabsorption and increases excretion renally; thus, in patients with hyperparathyroidism and increased PTH, plasma phosphate may be low. On the other hand, patients lacking proper parathyroid function may suffer from hyperphosphatemia. – Increased renal loss can be seen in the postoperative or trauma patient, as well as hypomagnesemia and volume expansion.

DISEASE/PATHOPHYSIOLOGY

• Hyperphosphatemia occurs with either increased absorption, increased release of skeletal phosphate, and/or decreased excretion. – Renal failure with a GFR <25 mL/min impairs normal excretion. – Hypoparathyroidism is often associated with hypocalcemia. – Tissue damage or cell death from hematologic malignancies with high cell turnover, cell destruction, and/or tumor lysis syndrome. – Other causes include iatrogenic hyperphosphatemia (i.e., parenteral administration in total parenteral nutrition [TPN], cathartics, medications with vitamin D), hypothermia, malignant hyperthermia, rhabdomyolysis, and massive liver failure. • Hypophosphatemia is severe when levels decrease to <1 mg/dL, respiratory or cardiovascular symptoms manifest, and/or cellular dysfunction is present. – Increased cellular uptake of phosphate from the extracellular compartment across the cell membrane is the most common cause in hospitalized and critically ill patients. – Etiologies of phosphate redistribution include carbohydrate-induced hypophosphatemia, refeeding syndrome or TPN therapy, treatment of diabetic ketoacidosis, diuretics or steroid therapy, osmotic diuresis, acidosis, tetany, and catabolic states. – Septic, trauma, and other patients with high catecholamine states (endogenous and/or exogenous epinephrine and norepinephrine) are prone to decreases in serum phosphate. – Prolonged respiratory alkalosis can cause cellular uptake of phosphate due to imbalances in intracellular pH and increased glycolysis. Phosphate continues to decrease even after hyperventilation ceases. Furthermore, the respiratory alkalosis associated with sepsis in gram-negative bacteremia and salicylate poisoning may explain the hypophosphatemia seen in these patients. – Hyperthermia and recovery from exhaustive exercise. – Poor dietary uptake and malnutrition such as in hospitalized alcoholic patients (50%) results in total body deficiency. – Depletion of phosphate in the form of 2,3-DPG shifts the oxygen dissociation curve to the left, leading to decreased tissue delivery of oxygen. – Decreased phosphate in the form of ATP leads to a lack of energy. This can exacerbate respiratory failure due to muscle weakness and diminish energy available for myocardial tissue. – Hypophosphatemic syndrome includes phosphate trapping, rhabdomyolysis, cardiomyopathy, respiratory insufficiency from profound muscle weakness, erythrocyte and leukocyte dysfunction, skeletal demineralization, metabolic acidosis, and nervous system dysfunction.

PERIOPERATIVE RELEVANCE

• Manifestations of hyperphosphatemia are primarily related to the formation of calcium phosphate salts and the subsequent development of hypocalcemia. Treatment includes the following: – Correcting the underlying etiology. – Reducing dietary intake, decreasing iatrogenic/parenteral supply, and augmenting dietary loss with enteric dietary phosphate binders (i.e., calcium acetate, calcium carbonate, aluminum hydroxide, or sevelamer) may be beneficial. – Increasing renal excretion by saline volume expansion and/or diuresis. If appropriate indication exists, renal replacement therapy may be needed or adjusted. • Hypophosphatemia is more commonly seen in the perioperative period. In critically ill patients, incidence ranges from 44–68% and is associated with increased mortality. – Pulmonary complications include respiratory muscle dysfunction, which leads to acute respiratory muscle failure and difficulty liberating patients from mechanical ventilation. – Myocardial dysfunction is not uncommon with manifestations of arrhythmias, decreased contractility, and acute heart failure. – Neurologic manifestations include paresthesia, myopathy, encephalopathy, delirium, seizures, and coma. – Muscle weakness and malaise is also common with rhabdomyolysis resulting from severe hypophosphatemia. – Hematologic abnormalities include dysfunction of all cell lines (erythrocytes, platelets, and leukocytes). – Immune dysfunction may occur as a result of impaired chemotactic, phagocytic, and bactericidal activity of granulocytes. • Cardiac surgery: In patients undergoing elective cardiac surgery, 34.3% of patients suffered from postoperative hypophosphatemia (1). – Hypophosphatemia was associated with prolonged ventilation, increased requirement of inotropic support, and prolonged hospital stay. – Blood, plasma, and platelet transfusions were associated with decreased postoperative phosphate levels. • Hepatic surgery: In patients undergoing major hepatic surgery, the incidence of hypophosphatemia was 67% in one series (2), while another series showed decreased phosphate levels in all patients undergoing hepatic lobectomy (3). – Postoperative complications were more prevalent in patients with hypophosphatemia. – Proposed mechanisms include intracellular shifts into hepatocytes and renal phosphate wasting. – Antacids were associated with increased postoperative hypophosphatemia. • Trauma – The incidence of hypophosphatemia and other electrolyte abnormalities is higher in patients with severe head injury than with patients without significant head injury (4). – Hypothermic protocols for neuro-protection in patients with severe head injury further exacerbate hypophosphatemia (5). • Kidney transplant recipients are also prone to hypophosphatemia due to multiple mechanisms that are not clearly understood.

• In patients with the potential for refeeding syndrome, it is best to initially avoid glucosecontaining fluids and then reintroduce them slowly. – Since the electrolyte abnormalities (hypophosphatemia, hypokalemia) occur due to increased cellular uptake–associated glucose and insulin, avoiding glucose-containing substances can alleviate electrolyte derangements. – If there is evidence of refeeding syndrome, nutrition should be started slowly and advanced only after electrolytes are stabilized.

EQUATIONS

• Phosphate replacement can be made in the form of both sodium phosphate and potassium phosphate, either orally or parenterally. The desired amount to be administered can be achieved by multiplying the volume of distribution (400 mL/kg) by the desired change. The rate of IV administration should not exceed 0.25 mmol/kg over 4–6 hours to avoid hypocalcemia and tissue damage. • In patients with hyperkalemia or risk factors for hyperkalemia, sodium phosphate may be preferred over potassium phosphate.

REFERENCES

1. Cohen J, Kogan A, Sahar G, et al. Hypophosphatemia following open heart surgery: Incidences and consequences. Eur J Cardiothorac Surg. 2004;26(2):306–310. 2. Buell JF, Berger AC, Plotkin JS, et al. The clinical implications of hypophosphatemia following major hepatic resection or cryosurgery. Arch Surg. 1998;133(7):757–761. 3. George R, Shiu MH. Hypophosphatemia after major hepatic surgery. Surgery. 1992;111(3):281–286. 4. Polderman KH, Bloemers FW, Peerdeman SM, et al. Hypomagnesemia and hypophosphatemia at admission in patients with severe head injury. Crit Care Med. 2000;28(6):2022–2025. 5. Polderman KH, Peerdeman SM, Girbes AR. Hypophosphatemia and hypomagnesemia induced by cooling in patients with severe head injury. J Neurosurg. 2001;94(5):697–705. 6. Geerse DA, Bindels AJ, Kuiper MA, et al. Treatment of hypophosphatemia in the intensive care unit: A review. Crit Care. 2010;14(4):R147. See Also (Topic, Algorithm, Electronic Media Element) • Trauma • Renal transplant • End stage renal disease

CLINICAL PEARLS

• Hypophosphatemia is prevalent in patients undergoing major surgery, including cardiac surgery, hepatic surgery, abdominal aorta surgery, trauma, and burn victims. • Identifying patients at risk for hypophosphatemia (i.e., post-surgical, malnourished) allows for earlier detection and prompt treatment to prevent major complications, especially

respiratory failure, cardiac failure, and mortality. • Correction of hypophosphatemia with large doses of intravenous phosphate can lead to hypocalcemia by precipitation of calcium phosphate salts. Electrolytes should be monitored either during or after replacement of phosphate.

PIERRE ROBIN SEQUENCE Mohamad Iravani, MD Swati Patel, MD

BASICS DESCRIPTION

• Pierre Robin syndrome presents as a variable degree of micrognathia (resulting from mandibular aplasia), glossoptosis, and cleft palate. • The cardiovascular and neuromuscular systems may also be affected. • Synonyms: Pierre Robin sequence; Pierre Robin malformation; Robin sequence; Pierre Robin anomalad EPIDEMIOLOGY Prevalence

May occur in isolation or as part of a more complex syndrome (Stickler syndrome, cerebrocostomandibular syndrome, velocardiofacial syndrome, fetal alcohol syndrome and trisomy 18). Greater than 80% occur as part of a syndrome. Prevalence

• Ranges from 1 in 8,500 to 1 in 20,000 children. • The male to female ratio is one-to-one.

Morbidity

Airway obstruction and failure to thrive Mortality

A mortality of 2.2–26% has been reported in the literature. ETIOLOGY/RISK FACTORS

The etiology of Pierre Robin sequence is unclear but it may be associated with the deletion 2q32.2–33.2 PHYSIOLOGY/PATHOPHYSIOLOGY

• The term Pierre Robin sequence, in place of a syndrome, was introduced because a sequence of events leads to the anomaly rather than a constellation of anomalies. • Mandibular hypoplasia is the initial event that leads to the posterior placement of the tongue (glossoptosis) and loss of support and coordination of the genioglossi muscles. – Thus, on inspiration, the tongue is further displaced posteriorly, worsening airway obstruction. – Chronic obstruction can lead to failure to thrive, pulmonary hypertension, and cor pulmonale.

• Cleft palate results from the failure of the tongue to descend during development, which interferes with the midline fusion of palatal shelves. • Severe airway obstruction may require immediate intervention at birth. Prone or lateral position may assist in maintaining airway patency (these patients may necessitate induction and intubation in the lateral or prone position). • Subsequent growth of the mandible, development of voluntary tongue control, and improved coordination of the parapharyngeal muscles occurring over the first years of life leads to lessening of the airway obstruction.

ANESTHETIC GOALS/GUIDING PRINCIPLES

Preservation of a patent airway is the main perioperative goal; the posterior positioning of the tongue, combined with micrognathia requires special consideration. • Induction: Maintenance of spontaneous ventilation with adequate ventilation and oxygenation must be ensured until the airway is secured. • Extubation: Patients must be fully awake and have full reversal of muscle relaxation. In addition, tongue stitches, careful monitoring, and emergency airway equipment need to be considered. • Elective tracheostomy may be considered for patients with severe obstruction especially if the patient will need multiple surgeries or to prevent chronic obstruction and development of pulmonary hypertension.

PREOPERATIVE ASSESSMENT SYMPTOMS

• May range from none to severe airway obstruction resulting in respiratory distress, hypoxia, and hypercarbia. • Severe disease may be associated with feeding difficulties and resultant failure to thrive.

History

• History of apnea and obstruction including the position required for airway patency. • Need for supplemental oxygen. • Full cardiac history to rule out associated congenital heart disease. • Record of previous anesthetics should be obtained for relevant information regarding airway management.

Signs/Physical Exam

• Vital signs • Patient position necessary for airway patency • Degree of airway obstruction and retractions • Degree of mandibular hypoplasia and tongue position • Assessment for cardiac murmur • Presence of any other anomalies

TREATMENT HISTORY

• Nasopharyngeal airway, lip–tongue adhesions, or urgent tracheostomy may be necessary if patient positioning fails to improve the obstruction. • Mandibular distraction has been used successfully to alleviate airway obstruction and avoid tracheostomy. Note that while distraction of the mandible can decrease the degree of obstruction, it may not change the Cormack and Lehane grade classification for grading the view of direct laryngoscopy. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

As indicated by the severity of symptoms and co-morbidities • Echocardiography • CXR (hyperventilation, pneumonia, CHF) • Arterial or venous blood gas

CONCOMITANT ORGAN DYSFUNCTION

• Ocular diseases such as congenital glaucoma and retinal detachments • Sensorineural hearing loss • Pulmonary hypertension, cor pulmonale from chronic hypoxia

CIRCUMSTANCES TO DELAY/CONDITIONS

Any evidence of a recent URI such as rhinorrhea, abnormal lung sounds, or a cough might justify a postponement of elective surgery.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Due to the high incidence of airway obstruction, preoperative benzodiazepines should be avoided or used with extreme caution depending on the index of suspicion. • Peripheral access should be obtained and anti-cholinergics should be given to decrease oral secretions and to counteract the vagal hyperreflexia present in these patients.

Special Concerns for Informed Consent

Airway management can be extremely difficult and parents should be accordingly informed of the possible loss of airway and its consequences, including the need for emergent tracheostomy. INTRAOPERATIVE CARE Choice of Anesthesia

Consider regional anesthetic techniques whenever possible, so as to avoid airway instrumentation. Monitors

• Consider augmenting the ETCO2 waveform size on the monitor (slow rise to peak indicates expiratory obstruction) • Consider an arterial line in high-risk patients (for serial ABGs)

Induction/Airway Management

• Unless previous anesthetic records document the ability to mask ventilate and intubate or the index of suspicion based on physical examination is reasonably low, fiberoptic intubation with maintenance of spontaneous respirations is strongly recommended (consider awake nasal or oral fiberoptic intubation). • It is crucial to have a plan before induction; appropriate equipment including a tracheostomy tray and adequate personnel must be available. • The main goal is preservation of spontaneous ventilation; therefore muscle relaxants should be avoided until the airway is secured. • Topicalization of the airway with nebulized 4% lidocaine is beneficial for blunting airway responses to intubation (care must be taken to avoid toxicity in small infants). • The choice of anesthetic regimen for sedation during intubation is crucial. The key is to maintain an adequate depth of anesthesia to prevent laryngospasm without loss of spontaneous respiratory effort. – Sevoflurane and propofol have been used successfully but caution must be used as both may cause airway obstruction and/or apnea. – Ketamine and/or dexmedetomidine have been used successfully in this setting. Ketamine and dexmedetomidine both preserve spontaneous respiration while providing adequate anesthesia. When used together, dexmedetomidine may offset the excess oral secretions and sympathomimetic effects of ketamine. • The narrowed pharyngeal space (secondary to small jaw and relatively large posteriorly located tongue) can add an additional challenge for fiberoptic intubation. During intubation, consider: – Additional skilled personnel to provide jaw thrust – Tongue “retraction” anteriorly using towel clamp, tongue stitch, or gauze. Care must be taken to minimize trauma to the tongue. • Fiberoptic endotracheal intubation through a laryngeal mask airway has been successfully described. • Indirect videolaryngoscopy can also be utilized, as it allows a more anterior view of the airway. • Once the airway is established and appropriate position is confirmed, consider suturing the ETT in place for added security.

Maintenance

Consider steroid (dexamethasone) administration if airway edema is anticipated. Extubation/Emergence

• Extubation should be carried out only when the patient is fully awake with regular breathing and adequate tidal volumes. • A tongue stitch may aid in maintaining a patent airway postoperatively.

FOLLOW-UP BED ACUITY

• One-to-one nursing in an ICU setting is mandatory to allow for close monitoring of respiratory issues. • Emergency airway equipment should be immediately available.

MEDICATIONS/LAB STUDIES/CONSULTS

• No particular medications are indicated for Pierre Robin. • Arterial blood gas may provide guide to degree of airway obstruction. • For patients with severe obstruction or known difficult airway, consider ENT consult or standby in the operating room for potential urgent/emergent tracheostomy.

COMPLICATIONS

The main complications are associated with loss of airway and the subsequent hypoxia/anoxia.

REFERENCES

1. Bush PG, Williams AJ. Incidence of the Robin Anomalad (Pierre Robin syndrome). Br J Plast Surg. 1983;36:434–437. 2. Rintala A, Ranta T, Shears T. On the pathogenesis of cleft palate in the Pierre Robin syndrome. Scand J Plast Reconstr Surg. 1984;18:237–240. 3. issonnette B. Syndromes: Rapid recognition and perioperative implications. McGraw-Hill Companies, Inc. 2006. 4. Iravani M, Wald SH. Dexmedetomidine and ketamine for fiberoptic intubation in a child with severe mandibular hypoplasia. J Clin Anesth. 2008;20(6):455–457. 5. Van den Elzen APM, Semmekrot BA, Bongers EMHF, et al. Diagnosis and treatment of the Pierre Robin Sequence: Results of a retrospective clinical study and review of the literature. Eur J Pediatr. 2001;160:47–53. See Also (Topic, Algorithm, Electronic Media Element)

• Tracheostomy • Difficult airway • Cleft palate

CODES ICD9 756.0 Anomalies of skull and face bones ICD10 Q87.0 Congen malform syndromes predom affecting facial appearance

CLINICAL PEARLS

• Maintain spontaneous ventilation until the airway is secured or the ability to bag mask ventilate is confirmed. • Consider suturing the tube for the duration of the procedure. • Consider a tongue stitch for the postoperative period to decrease obstruction. • Always have equipment ready for re-intubation.

PLACENTA ACCRETA Izabela M. Wasiluk, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Placenta accreta refers to the abnormally deep and firm attachment of the placenta to the uterine wall. This may lead to massive, life-threatening hemorrhage during manual placental separation. • The differential diagnosis of placenta accreta includes other causes of postpartum hemorrhage: – Uterine: Atony, rupture, inversion, retention of placental products – Non-uterine: Vaginal tears, perineal hematoma, coagulopathy • When discovered early, an elective Cesarean section/hysterectomy may be performed in a more controlled situation: – Can be scheduled at a facility capable of managing postpartum hemorrhage. – A multidisciplinary team can be scheduled to be in the operating room (obstetrician, anaesthetist, neonatologist, interventional radiologist). – Uterine preservation may be considered. – Type and crossed blood products can be in the room and ready for transfusion; a cell saver can be set up and ready for use. The blood bank should be informed. – Techniques to decrease blood loss may be implemented, including leaving the placenta in situ. – An epidural catheter may be considered as opposed to general anesthesia. • However, when diagnosed at the time of, or after, placental separation, the delivery of care becomes emergent and challenging to members of the health team. In addition, maternal morbidity and mortality increase. EPIDEMIOLOGY Prevalence

• In the US: Occurs in 1 of 2,500 deliveries • Increased association in women with placenta previa: Approaches 10% of cases (1) • Increased 10-fold in the past 50 years due to the increased frequency of Cesarean sections. – Unscarred uterus: 3% (2) – ≥5 prior Cesarean sections: 67%

Prevalence

Cesarean sections have increased due to maternal obesity, multiple gestations (assisted reproductive technology), concern about litigation, and decreases in the use of operative vaginal delivery for cephalic and breech presentations (5)

Morbidity

• Hysterectomy, loss of fertility • Coagulopathy, DIC • Hypotension

Mortality

Maternal mortality rate is 7% ETIOLOGY/RISK FACTORS

• Number of Cesarean sections (relative risk 11.32) (1). • Advanced maternal age >35 years (relative risk 4.45) • Placenta previa (relative risk 2.28). • Previous myomectomy

PHYSIOLOGY/PATHOPHYSIOLOGY

• Normally, the layer of the decidua basalis prevents the attachment of placental villi through the endometrium and into the myometrium. Thus, at delivery, the placenta can readily detach from the uterine wall. • In placenta accreta, deeper invasion by trophoblasts may occur in thin, poorly formed decidua, as seen in the lower segment of the uterus or related to prior hysterotomy scars. • This may lead to failure of the placenta to separate after delivery, or uncontrolled bleeding when it does.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Management and outcome depend upon when the placenta accreta is diagnosed. Common to both scenarios is the need for a multidisciplinary team. • When diagnosed early, or before placental separation, surgical management often involves an elective Cesarean hysterectomy. Procedures or techniques to decrease blood loss include intrauterine artery balloon catheterization for ligation and/or reversible embolization, endouterine square hemostatic sutures, and leaving the placenta in the uterus during the hysterectomy. • There has been a recent trend toward conservative management/uterine preservation in an attempt to preserve fertility. This involves implementing some of the above-mentioned techniques that decrease blood flow to the uterus, thus allowing separation of the placenta. • In both scenarios, the anaesthetist must be prepared to treat postpartum hemorrhage. This can involve the transfusion of multiple units of blood products, as well as the use of a cell saver, antifibrinolytics, or recombinant factors. Large-bore IV access is necessary. • The decision to provide anesthesia via an epidural or general anesthesia is dependent upon several factors: Elective versus emergent, volume status, altered mental status, development of a coagulopathy, and comfort of the anaesthetist and patient.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Usually signs and symptoms are not detected until labor and delivery. • Third trimester vaginal bleeding can be noted.

History

• Prior Cesarean section, placenta previa, myomectomy, or manual removal of the placenta • Advanced maternal age

Signs/Physical Exam

• Profuse vaginal bleeding during manual separation of the placenta after delivery • Non-delivery of the placenta in a half-hour post delivery.

TREATMENT HISTORY

See techniques for decreasing blood loss MEDICATIONS Not applicable

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• 45% women with placenta accreta were found to have elevated serum alpha-fetoprotein levels. • Definitive diagnosis can be made only on histologic examination. • Ultrasonography has a relatively high sensitivity (0.77) and specificity (0.96). • MRI increases diagnostic accuracy in cases when ultrasonography is inconclusive (sensitivity 0.88, specificity 1.0) (3).

CONCOMITANT ORGAN DYSFUNCTION

• Possible invasion into the myometrium or the serosa and surrounding structures. • Disseminated intravascular coagulopathy (DIC)

CIRCUMSTANCES TO DELAY/CONDITIONS

• In elective cases, all members of the multidisciplinary team should be available. In addition, cell salvage, blood products that are type and crossed, and possibly recombinant factors or antifibrinolytics should be present before proceeding. • In emergent cases, any delay should be avoided.

CLASSIFICATIONS

Three variants of the condition are recognized on the basis of the degree of placental penetration of the myometrium: • Placenta accreta: Chorionic villi abnormally adhere to the myometrium. • Placenta increta: Villi invade the myometrium. • Placenta percreta: Villi penetrate through the uterine serosa and may adhere to surrounding structure.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Gastric volume and acid reducing medications in elective cases. • In emergent cases, fluid resuscitation (crystalloid, colloid, transfusion products) and vasopressor therapy, should be started, as appropriate. Special Concerns for Informed Consent

• In elective cases, a discussion about invasive monitoring, transfusion of blood products, and choice of anesthesia should be discussed. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia is usually administered, in particular, for emergent cases. • If a laboring epidural is in place, continuous epidural anesthesia may be used for many cases of elective Cesarean hysterectomy (4). Conversion to general anesthesia, however, may be warranted in hemodynamically unstable patients secondary to massive peripartum hemorrhage with cardiovascular decompensation Monitors

• Standard monitors • Two large-bore IVs • Arterial line for BP monitoring and frequent lab draws. Consider noninvasive cardiac output monitoring (NICOM) for monitoring CO, CI, PVR, and PVRI. • Central line placement may be considered for large-bore access, pressure monitoring, and the administration of medications (e.g., vasopressors). Induction/Airway Management

• General anesthesia: A rapid sequence induction should be performed, after the abdomen is prepped and the surgical team, blood products, and other personnel are in the room. The goal is to minimize the time from induction to delivery and hence anesthetic drug exposure to the fetus. • Laboring epidural in place: Bolus with local anesthetic and confirm an adequate T6 level.

Maintenance

• If the accreta is found co-incidentally during a Cesarean section, the interventional radiologist should be informed so that procedures to decrease blood loss before hysterectomy/placental separation can be performed. • Blood product transfusion may be guided by hematocrit/hemoglobin levels, platelet values, coagulation profile, thromboelastogram, and/or clinical judgment. • Cell saver allows for autologous blood to be returned to the patient after being suctioned from the field, washed, and filtered. It requires a technician to set up and manage. When large volumes of blood are auto-transfused, a coagulopathy may result from the loss of

clotting factors and platelets. • Recombinant-activated factor VII is a potent procoagulant that bypasses parts of the coagulation cascade. It is commonly used for hemophilia, but off-label uses include the treatment of refractory bleeding. Studies suggest that there is a more favorable outcome when it is administered early in the course of refractory hemorrhage, rather than as a last resort. Risk may be prohibitive if the patient is at high risk for thromboembolic complications or has developed disseminated intravascular coagulation. • Tranexamic acid (TA) is a synthetic lysine analog that can be used prophylactically for refractory bleeding. TA acts reversibly by inhibiting the binding of plasminogen to charged lysine sites on the surface of fibrin molecules; thus it prevents the conversion of plasminogen to plasmin.

Extubation/Emergence

• Extubation may be considered if the patient is: – Hemodynamically stable – Volume repleted – Without airway edema from the large fluid shifts – Other extubation criteria are met • If an epidural catheter is in place, and a coagulopathy is suspected, it should not be removed until fully resolved, and PT/PTT/INR are within normal limits.

FOLLOW-UP BED ACUITY

Intensive care unit should be available for direct transfer. MEDICATIONS/LAB STUDIES/CONSULTS

• CCU bed with hemodynamic monitoring • Maintain oxygenation, circulation, control of hemorrhage, and coagulopathy

COMPLICATIONS

• Hemorrhagic shock, cardiovascular collapse • Uterine atony • Coagulopathy/DIC • Hysterectomy

REFERENCES

1. Miller DA, Chollet JA, Goodwin TM. Clinical risk factors for placenta previa – placenta accreta. Am J Obstet Gynecol. 1997;177:210–214. 2. Silver RM, Landon MB, Rouse DJ, et al. Maternal morbidity associated with multiple repeat cesarean deliveries. Obstet Gynecol. 2006;107(6):1226–1232. 3. Warshak CR, Eskander R, Hull AD, et al. Accuracy of ultrasonography and MRI in the diagnosis of placenta accreta. Obstet Gynecol. 2006;108:573–581.

4. Chestnut DH, Dewan DM, Redick LF, et al. Anesthetic management for obstetric hysterectomy: A multiinstitutional study. Anesthesiology. 1989;70:607–610.

5. Warshak CR, Ramos GA, Eskander R, et al. Effect of predelivery diagnosis in 99 consecutive cases of placenta accreta. Obstet Gynecol. 2010;115(1):65–69. 6. Hull AD, Moore TR. Multiple repeat cesareans and the threat of placenta accrete: Incidence, diagnosis, management. Clin Perinatol. 2011;38(2):285–296.

7. John J Sciarra. Gynecology and Obstetrics. Philadelphia, PA: Lippincott, Williams and Wilkins, 2000.

• Robert Resnick. Diagnosis and Management of Placenta Accreta. UpToDate.

See Also (Topic, Algorithm, Electronic Media Element) • Placenta previa • Cell savage • Antifibrinolytics • Recombinant-activated factor VII • Hysterectomy

CODES ICD9 667.00 Retained placenta without hemorrhage, unspecified as to episode of care or not applicable ICD10 • O43.211 Placenta accreta, first trimester • O43.212 Placenta accreta, second trimester • O43.219 Placenta accreta, unspecified trimester

CLINICAL PEARLS

• Placenta accreta may cause major postpartum bleeding. • Women with placenta previa and/or a history of prior Cesarean deliveries are at increased risk of placenta accreta. • A Cesarean section combined with a hysterectomy (placenta left in situ) is frequently necessary, although uterine conservation may be considered in select cases. • A multidisciplinary approach and rapid resuscitation efforts are required in order to have a desirable clinical outcome.

PLACENTA PREVIA Peter H. Kim, MD Mark Zakowski, MD

BASICS DESCRIPTION

• Placenta previa is a condition in pregnancy where the placenta overlies all or part of the internal os of the cervix. – A total placenta previa completely covers the cervical os. – A partial placenta previa covers only a portion of the cervical os. – A marginal or a low-lying placenta previa only encroaches on the edge of the internal cervical os. EPIDEMIOLOGY Prevalence

In the US: 2.8/1,000 live births (1)

Morbidity

• Complete or partial placenta previa is an absolute indication for Cesarean delivery. Cervical dilation with labor will lead to spontaneous, life-threatening maternal hemorrhage. • According to the World Health Organization (WHO), placenta previa is the number one risk factor for blood transfusion in obstetrics. • There is an increased risk of placenta accreta (where the placenta is attached too deep in the uterine wall) in parturients with a placental previa. This causes difficulty with the placental detachment. Hemorrhage can occur during manual attempts to detach the placenta, resulting in the need for a hysterectomy. In parturients with placenta previa, placenta accreta can occur in: – ∼3% who have had an unscarred uterus – ∼11% who have had a previous Cesarean section – ∼40% who have had two previous Cesarean deliveries Mortality

• Maternal mortality rate: 0.03% of all births in the US. The majority of deaths are attributed to maternal hemorrhage and disseminated intravascular coagulation (DIC) (3). • Neonatal mortality: 10.7/1000 births. The majority of deaths are attributed to prematurity and/or fetal growth restriction (1). ETIOLOGY/RISK FACTORS

• The etiology of placenta previa is unknown. • Risk factors include: Previous placenta previa, presence of a uterine scar, multiparity, multiple gestation, and advanced maternal age.

– Women >35 years old are ∼3 times more likely to have placenta previa than women <25 years old (4).

PHYSIOLOGY/PATHOPHYSIOLOGY

No specific cause has been identified to date

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Evaluate maternal airway in the event that a general anesthetic must be performed emergently. • Regional anesthesia is preferred. General anesthesia carries a 1.7 times increased risk of maternal mortality (5) due to airway complications. Parturients are more likely to have airway edema and difficulty with mask ventilation and intubation; this is combined with a decreased functional residual capacity (FRC) and increased oxygen demand. • Prepare for maternal hemorrhage. – Ensure adequate IV access. – Type and cross for blood. – In the operating room, O-negative or crossmatched (preferred) packed red blood cells, as well as fresh frozen plasma, platelets, and possibly activated factor VII need to be immediately available. • Identify the position of the placenta to assess the risk of placenta accreta; there is an increased risk if the placenta overlies a previous uterine scar.

PREOPERATIVE ASSESSMENT SYMPTOMS

Lightheadedness or dizziness History

• Timing of bleed: Vaginal bleeding from placenta previa generally occurs in the second or third trimester. • Painless vaginal bleeding: In contrast, placental abruption is characterized by vaginal bleeding with painful contractions. Bleeding from a placenta previa may spontaneously stop but it will recur. • History of a prior uterine surgery and/or injury: There is an increased risk of placenta accreta if a placenta previa occurs in the presence of a prior uterine scar.

Signs/Physical Exam

• Painless vaginal bleeding • Hypotension • Tachycardia • Non-reassuring fetal heart tracing

MEDICATIONS

• If the diagnosis of placenta previa is made between 24 and 34 weeks gestation, corticosteroids may be administered to accelerate fetal lung maturity. Patients with placenta

previa are prone to preterm labor. • Volume resuscitation

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Assess the severity of hemorrhage: Hemoglobin/hematocrit. Values may be falsely elevated if adequate fluid resuscitation has not occurred. • Evaluate coagulation status: Platelets, PT/PTT, INR, fibrinogen. • Type and cross • Abdominal ultrasound: Confirms the presence and type of placenta previa. Evaluate the risk of placenta accreta. • No vaginal examinations should be performed if there is a suspected previa.

CIRCUMSTANCES TO DELAY/ CONDITIONS

If the parturient is hemodynamically stable and vaginal bleeding is controlled. Cesarean delivery should be delayed to allow for fetal lung maturity. CLASSIFICATIONS

Marginal, partial, total

TREATMENT • Cesarean delivery is indicated in the presence of complete or partial placenta previa. – Timing of delivery is determined by the fetal and maternal status.

PREOPERATIVE PREPARATION Premedications

• Anti-aspiration precautions: Sodium bicitrate, cimetidine, and/or metoclopramide. • Avoid benzodiazepines and opioids; they can cross the placenta and contribute to neonatal depression. • Type and cross 4–6 pRBC units; may need to transfuse O-negative uncrossmatched blood in an emergency. Consider rapid transfusion devices or cell saver.

Special Concerns for Informed Consent

• Conversion to general anesthesia if the patient is hemodynamically unstable. • Possible need for transfusion of blood products. • Possible need for placement of invasive monitors including arterial catheter and/or central venous catheterization.

INTRAOPERATIVE CARE Choice of Anesthesia

• Neuraxial anesthesia preferred. • General anesthesia indicated for actively bleeding, hemodynamically unstable patients.

Monitors

• Standard: Pulse oximetry, noninvasive BP, EKG, temperature, capnography. • Invasive monitors (arterial catheter, CVP) if indicated.

Induction/Airway Management

• Regional anesthesia is preferred. • Rapid-sequence intubation if general anesthesia is indicated. – Etomidate (0.3 mg/kg) or ketamine (1.5 mg/kg) preferred for hemodynamically unstable patients. – Be prepared for difficult intubation. There is a 7-fold increase in failed intubation in the parturient population. – Succinylcholine, a depolarizing muscle relaxant, is preferred (1–1.5 mg/kg). The greater blood volume is countered by the lower concentration of plasma pseudocholinesterase (metabolizes succinylcholine) during pregnancy.

Maintenance

• The neonatal team should be in the room. • General anesthesia is maintained with a combination of volatile anesthetic and nitrous oxide. Following delivery of the fetus, decrease the volatile anesthetic to <0.5 MAC to minimize decrease in uterine tone. • Opioids: IV or epidural dosing can be given following clamping of the cord. • Muscle relaxation: Non-depolarizing muscle relaxants may be used to facilitate closure; dosage is not altered for the parturient. • Volume status – Aggressively titrate fluids to maintain hemodynamic stability (BP >100 mm Hg, HR <120) and urine output (>0.5 mL/kg/hr). Consider early use of colloids (e.g., Hetastarch 6% or albumin 5%). – Blood loss may be difficult to assess visually (typically underestimated by 33–50%) (6). All blood loss should be quantitated, including weighing laparotomy sponges and bed underpads. – In the case of massive transfusion, the recommendation is that pRBCs and fresh frozen plasma are given in a 1:1 ratio; one unit of platelets is given for every 4 units of pRBCs. • Normothermia: Utilize fluid warmers as well as forced air warming blankets. There is an increased tendency for hypothermia and shivering (increased metabolic demand) with massive blood loss and fluid replacement. • Uterotonics to reduce bleeding after delivery: – Oxytocin; proceed with additional agents after 20 units – Methylergonovine 0.25 mg IM (do not administer IV) – 15-methyl prostaglandin F2-alpha 250 mcg IM or directly into the uterus – Misoprostol 1000 mcg may be placed rectally (prostaglandin E1 derivative) • Alternate techniques to control hemorrhage – Arterial embolization in the radiology suite – Intrauterine balloon tamponade – Surgical ligation of uterine and hypogastric arteries may slow down the bleeding.

Extubation/Emergence

• Extubation criteria include adequate oxygenation, adequate ventilation, and ability to protect the airway. • Consider orogastric tube suctioning prior to extubation to reduce the gastric volume. • Prophylactic antiemetics

FOLLOW-UP BED ACUITY

• Monitor for continued or recurrent bleeding and DIC in the recovery room and postpartum period. • In the setting of moderate to severe hemorrhage, consider higher acuity care until hemodynamically stable or no further bleeding for several hours.

MEDICATIONS/LAB STUDIES/CONSULTS Follow Hb/Hct and coagulation status. COMPLICATIONS

• Maternal hemorrhage – Poor contractility of the lower uterine segment following separation of the placenta previa may lead to increased blood loss. – Increased risk of entering the placenta with uterine incision at Cesarean delivery. – Increased risk of placenta accreta in the setting of placenta previa. – If bleeding is uncontrolled, may necessitate ligation of uterine vessels or hysterectomy. • Disseminated intravascular coagulation (DIC)

REFERENCES

1. Ananth CV, Smulian JC, Vintzileos AM. The effect of placenta previa on neonatal mortality: A population-based study in the United States, 1989 through 1997. Am J Obstet Gynecol. 2003;188(5):1299–1304. 2. Silver RM, Landon MB, Rouse DJ, et al. Maternal morbidity associated with multiple repeat cesarean deliveries. Obstet Gynecol. 2006;107:1226–1232. 3. Crane S, Chun B, Acker D. Treatment of obstetrical hemorrhagic emergencies. Curr Opin Obstet Gynecol. 1993;5(5):675–682. 4. Zhang J, Savitz DA. Maternal age and placenta previa: a population-based, case-control study. Am J Obstet Gynecol. 1993;168(2):641–645. 5. Hawkins J, Chang J, Palmer S, et al. Anesthesia-related maternal mortality in the United States: 1979–2002. 6. Obstet Gynecol. 2011;117:69–74. 7. Lyndon A, Miller S, Huwe V, et al. CMQCC.org, Blood Loss: Clinical techniques for ongoing quantitative measurement. Available at : http://www.cmqcc.org/resources/916.

See Also (Topic, Algorithm, Electronic Media Element) • Placenta accreta • Difficult airway

CODES ICD9 • 641.00 Placenta previa without hemorrhage, unspecified as to episode of care or not applicable • 641.10 Hemorrhage from placenta previa, unspecified as to episode of care or not applicable ICD10

• O44.00 Placenta previa specified as w/o hemorrhage, unsp trimester • O44.10 Placenta previa with hemorrhage, unspecified trimester

CLINICAL PEARLS

• The hallmark of placenta previa is painless vaginal bleeding. Placenta previa can be classified as complete, partial, or low lying/marginal. In addition, it can be a risk factor for placenta accreta. • Bleeding typically stops, but may worsen with recurring episodes. • Vaginal examinations are contraindicated in the setting of a placenta previa. • Parturients with marginal or low-lying placenta previa may be considered for vaginal delivery. However, those with a complete or partial placenta previa must be delivered by Cesarean section. • Placenta previa is a risk factor for maternal hemorrhage. Adequate intravascular access should be attained and blood products should be immediately available.

PLACENTAL ABRUPTION Rajeshwary Swamidurai, MD

BASICS DESCRIPTION

• Placental abruption is the premature, complete, or partial separation of the placenta from the uterine wall prior to delivery of the fetus, after 20 weeks gestation. • It may be revealed by vaginal bleeding or remains concealed.

EPIDEMIOLOGY Prevalence

• Occurs in ∼0.5–1% of deliveries (1,2,3,4) • Rate of clinically detected abruptions have increased in the US, with a disproportionate increase seen in African-American women (1) • Incidence peaks between 24–26 weeks gestation, and decreases with advancing gestational age (2). Morbidity

• Maternal morbidity depends on the severity of the abruption and results from DIC, renal failure, transfusion reactions, ischemic necrosis of distal organs, hemorrhagic shock, uterine rupture, and uncontrolled hemorrhage resulting in hysterectomy (1,2,3). • Fetal morbidity depends on the location and severity of abruption, in addition to the gestational age of the fetus. It results from hypoxia, anemia, CNS anomalies, IUGR, SGA, preterm delivery or fetal death. Retroplacental abruptions have the worst prognosis (2).

Mortality

• Perinatal mortality has been reported as 11–12% (2,3).

ETIOLOGY/RISK FACTORS

• Maternal risk factors – History of prior abruption – History of smoking, cocaine, and substance abuse – Alcohol consumption – Hypertension or preeclampsia – Elevated 2nd trimester maternal AFP – Thrombophilias – Folate deficiency or Anemia (11) – Placenta previa or bleeding early in pregnancy – Uterine fibromyomas/tumors – Advanced maternal age – Higher mean levels of homocysteine

– Hospitalizations for acute and chronic respiratory diseases during pregnancy (9) • Procedural or situational risk factors – Trauma or domestic violence – Velamentous insertion of umbilical cord or short cord • Fetal-related risk factors – Multifetal gestation (or sudden decompression of the uterus) – Oligohydramnios – Preterm premature rupture of membrane – Intrauterine infections or chorioamnionitis – Male fetus

PHYSIOLOGY/PATHOPHYSIOLOGY

• Placental abruption most likely results from a cascade of underlying pathophysiological processes, and the precise mechanism remains elusive in many cases. Furthermore different mechanisms may be involved in preterm versus term abruptions . Inflammatory mediators present in both acute and chronic inflammatory processes, may play a role in increased premature production of matrix metalloproteinase-9, an enzyme that helps in the normal placental detachment following delivery (5). • Abnormal placental vasculature, thrombosis, and decreased placental perfusion may play a role in abruption on the basis of pathologic studies (3). Acute vasospasm of small vessels, coupled with thrombosis of decidual vessels may lead to necrosis and venous hemorrhage at the decidual placental interface, leading to uteroplacental insufficiency (2). In some cases, abnormal trophoblast invasion leading to rupture of spiral arteries and premature separation of the placenta may be responsible for abruption (6). • Cocaine is a vasoconstrictor and may cause vasospasm of uterine vessels leading to uteroplacental insufficiency and abruption (7). • Increased capillary frailty, changes in uteroplacental circulation, and arterial rupture may cause abruption in smokers (4). Nicotine’s effects may result from vasoconstriction of uterine and umbilical arteries, coupled with increased carboxyhemoglobin levels that compromise oxygenation, leading to hypoxia, placental microinfarctions, necrotic foci, and ultimately abruption (8). • Acute shearing forces may affect the placenta–decidua interface, leading to abruption. This occurs with rapid deceleration injuries or sudden decompression following membrane rupture of an over-distended uterus (polyhydramnios or multiple gestations).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Vaginal delivery may be considered if the mother is stable and the fetus is at term or near term with a reassuring fetal status. • In the absence of maternal hypotension, clotting abnormalities, or signs of fetal distress, labor analgesia may be provided by an epidural for vaginal delivery (2). • In cases of fetal death with severe abruption, vaginal delivery is possible, as long as the mother is stable. However, potential coagulopathy should be evaluated if considering an epidural.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Vaginal bleeding • Abdominal or back pain • Frequent uterine contractions • Fetal distress or fetal death

History

Elicit associated risk factors and symptoms since diagnosis is based mostly on clinical grounds. TREATMENT HISTORY

• Administer continuous high-flow supplemental oxygen • Maintain left uterine displacement • Monitor for bleeding and if DIC is present, correct coagulopathy prior to surgery, if possible • Monitor maternal vital signs and fetal heart tones continuously • Insert large bore IV lines and begin LR or NS infusion.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hemoglobin, hematocrit—to assess bleeding • Platelets, fibrinogen, FDP, PT, aPTT, D-dimer—to assess coagulopathy • BUN, electrolytes—to assess volume status/renal dysfunction • Blood type and cross match • Abdominal and vaginal ultrasound. Ultrasound is not sensitive but has a high PPV (10).

CONCOMITANT ORGAN DYSFUNCTION

DIC, Renal failure, Hemorrhagic shock, Uterine rupture, Uncontrolled hemorrhage, Ischemic necrosis of distal organs. CIRCUMSTANCES TO DELAY/CONDITIONS

• If the fetus is preterm, shows no signs of distress, and the abruption is minimal, then the patient may be hospitalized with conservative management, allowing pregnancy to continue in order to promote fetal lung maturity prior to delivery. The patient should be transferred to a facility with a neonatal unit capable of caring for a preterm baby. • If the mother is unstable, or the fetal status is non-reassuring, then delivery should be undertaken via prompt C-section (2).

CLASSIFICATIONS

Premature, complete, or partial separation

TREATMENT

PREOPERATIVE PREPARATION Premedications

Cross-matched blood, FFP, and platelets should be available if DIC is present. Special Concerns for Informed Consent

• Blood consent • Potential postoperative intubation • Planned or potential invasive monitoring

INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia is usually the preferred option for emergency C-section due to the potential underlying coagulopathy and hypovolemia from hemorrhage. Monitors

• In addition to routine monitors, central venous pressure monitoring may be helpful for fluid management. • An arterial line may be useful for continuous BP monitoring. • Foley catheter output may be useful to guide fluid status.

Induction/Airway Management

• Consider agents that maintain better hemodynamics such as ketamine or etomidate. • RSI with cricoid pressure should be considered on induction to minimize chances of aspiration. • Friable and edematous laryngeal mucosa, combined with underlying coagulopathy may result in uncontrolled hemorrhage during intubation. • Preparation for a difficult airway should include difficult airway equipment such as LMAs, intubating LMAs, flexible fiberoptic bronchoscope, and videolaryngoscopy, if available. • An awake fiberoptic intubation may be considered for a difficult airway if time permits.

Maintenance

• 50% nitrous oxide may be used along with oxygen and a reduced dose of volatile anesthetic prior to delivery. • Following delivery, nitrous oxide may be increased and the dose of volatile anesthetic may be lowered to promote uterine contractions. IV agents such as opioids and midazolam may be used to supplement anesthesia. • These patients are at increased risk for uterine atony, therefore oxytocin should be infused promptly after delivery.

Extubation/Emergence

• Bleeding should be controlled, hypovolemia and any coagulopathy should be corrected prior to extubation. • If the patient has undergone massive blood/products transfusion or fluid administration, or if there are signs of ongoing bleeding or coagulopathy, the patient should remain intubated

and transferred to the ICU.

FOLLOW-UP BED ACUITY

Most parturients improve following delivery, but if hypotension or coagulopathy persists, the patient should be admitted to a multidisciplinary ICU for continued observation and management. MEDICATIONS/LAB STUDIES/CONSULTS

• Oxytocin infusion may be continued in the postoperative period. • Fluid management and vigilant observation for further bleeding should be continued. Hemoglobin, hematocrit, and vital signs should be monitored. • Coagulation profile and D-dimer should be ordered if DIC is suspected.

COMPLICATIONS

• Uterus may be hypotonic following delivery and may necessitate an emergency hysterectomy. • Prolonged hypovolemia may result in ATN. • Coagulation cascade products may lead to renal cortical necrosis resulting in chronic renal failure. • Severe preeclampsia may be masked by hypovolemia in cases of massive hemorrhage, and therefore extra vigilance is required to avoid overlooking this diagnosis.

REFERENCES

1. nanth CV, Oyelese Y, Yeo L, et al. Placental abruption in the United States, 1979 through 2001: Temporal trends and potential determinants. Am J Obstet Gynecol. 2005;192:191– 198. 2. Oyelese Y, Ananth CV. Placental abruption. Obstet Gynecol. 2006;108(4):1005–1016. 3. Ananth CV, Wilcox AJ. Placental abruption and perinatal mortality in the United States. Am J Epidemiol, 2001;153:332–337. 4. Ananth CV, Smulian JC, Vintzileos AM, et al. Incidence of placental abruption in relation to cigarette smoking and hypertensive disorders during pregnancy: A meta-analysis of observational studies. Obstet Gynecol. 1999;93(4):622–628. 5. Ananth CV, Getahun D, Peltier MR, et al. Placental abruption in term and preterm gestations. Evidence for heterogeneity in clinical pathways. Am J Obstet Gynecol. 2006;107:785–792. 6. Elsasser DA, Ananth CV, Prasad V, et al. Diagnosis of placental abruption: Relationship between clinical and histopathological findings. Eur J Obstet Gynecol Reprod Biol. 2010;148(2):125–130. 7. Hoskins IA, Friedman DM, Frieden FJ, et al. Relationship between antepartum cocaine abuse, abnormal umbilical artery doppler velocimetry and placental abruption. Obstet

Gynecol. 1991;78(2):279–282. 8. Kaminsky LM, Ananth CV, Prasad V, et al. The influence of maternal cigarette smoking on placental pathology in pregnancies complicated by abruption. Am J Obstet Gynecol. 2007;197:275.e1–275.e5. 9. etahun D, Ananth CV, Peltier MR, Smulian JC, Vintzileos AM. Acute and chronic respiratory diseases in pregnancy: associations with placental abruption. Am J Obstet Gynecol. 2006;195:1180–1184. 10. lanz C, Purnell L. Clinical utility of sonography in the diagnosis and treatment of placental abruption. J Ultrasound Med. 2002;21:837–840.

11. nanth CV, Smulian JC, Demissie K, Vintzileos AM, Knuppel RA. Placental abruption among singleton and twin births in the United States: Risk factor profiles. American Journal of Epidemiology. 2001;153:771–778.

CODES ICD9

• 641.20 Premature separation of placenta, unspecified as to episode of care or not applicable • 641.23 Premature separation of placenta, antepartum condition or complication ICD10 • O45.90 Premature separation of placenta, unsp, unsp trimester • O45.91 Premature separation of placenta, unsp, first trimester • O45.92 Premature separation of placenta, unsp, second trimester

CLINICAL PEARLS

• In the presence of abruption, rule out DIC as a source of coagulopathy and hypovolemia from massive hemorrhage before performing spinal or epidural anesthesia. • Aggressive fluid and product resuscitation is required in the setting of massive hemorrhage or DIC to prevent long-term consequences.

PLASMA OSMOLALITY Erik Olness, MD Stephen O. Bader, MD

BASICS DESCRIPTION

• Osmolarity and osmolality are similar terms and are often used interchangeably. – Osmolarity is defined as the number of moles of solute in a liter of solution. – Osmolality refers to the number of moles of solute in a kilogram of solution; it is generally the preferred term Water’s molecular mass represents the number of water molecules more accurately than the volume (molecular mass does not change with temperature, whereas water volume does, albeit only slightly). 1 kg of water occupies exactly 1 L at 4%C, allowing the interchangeability of osmolality and osmolarity in most instances. • Osmoles are the number of unique particles into which a given substance dissociates in solution. – 1 mole of NaCl in solution contains 2 osmoles, since NaCl dissociates into Na+ and Cl− ions. – 1 mole of glucose in solution contains one osmole as glucose does not dissociate. • Freezing point depression osmometry is used to directly measure plasma osmolality. • Tonicity, a related term referring to the effect of a solution on cell volume, is often equated incorrectly with osmolarity or osmolality. PHYSIOLOGY PRINCIPLES

• An average adult male is ∼60% water by weight; females are 50% water. • Total body water (TBW) is divided into 2 major fluid compartments separated by cellular membranes: Intracellular fluid (ICF) and extracellular fluid (ECF). The ECF can be further divided into: – Intravascular fluid, contained within the vascular endothelium – Interstitial fluid, which includes all fluid outside of cells • The fluid volume contained in a given compartment is determined by the compartment’s solute concentration and composition. Differences in solute concentrations are largely due to the physical characteristics of the barriers separating compartments. The trapped solutes within compartments create osmotic forces that govern the distribution of water and ultimately compartment volume. • The cell membrane–bound Na+/K+ ATPase ion pump exchanges sodium (Na+) for potassium (K+) in a 3:2 ratio. 3 Na+ ions are transported extracellularly for 2 K+ ions transported intracellularly. – Cell membranes are relatively impermeable to Na+, and to a lesser extent K+, such that

Na+ is the most important determinant of extracellular osmotic pressure while K+ is the most important determinant of intracellular osmotic pressure. • Cells are impermeable to most proteins resulting in a high intracellular protein concentration. The anionic proteins are nondiffusible, making the unequal Na+/K+ exchange crucial in preventing intracellular hyperosmolality. • Fluid compartment exchange is primarily governed by diffusion through cell membranes and capillary endothelium. A substance’s rate of diffusion across a membrane depends on: – The substance’s permeability through a given membrane – The hydrostatic pressure difference between the two sides – The substance’s concentration difference – The electrical potential across the membrane for charged substances • The ECF’s osmolality is equal to the sum of the concentration of all dissolved solutes. – Na+ and its paired anions account for nearly 90% of the dissolved solutes in the ECF. – This makes the following approximation possible: Plasma osmolality ∼2 × Plasma Na+ concentration ([Na+]plasma). Measured plasma osmolality is normally 280–290 mOsm/L.

• TBW and Na+ balance are maintained in a tight range by the interaction of multiple neurohumoral mechanisms, including the renin–angiotensin– aldosterone system, the hypothalamic–pituitary axis, the atrial and brain natriuretic peptides, and the sympathetic nervous system. • The main regulatory mechanism for water metabolism is the pituitary secretion of antidiuretic hormone (ADH), also known as arginine vasopressin.

ANATOMY

• Osmoreceptors in the hypothalamus closely regulate plasma osmolality by controlling the secretion of ADH and the thirst mechanism. – The osmoreceptors can detect changes in osmolality as small as 1–2%. – When ECF osmolality increases, these hypothalamic cells shrink and trigger the release of ADH from the posterior pituitary. – ADH is produced in the supraoptic and paraventricular nuclei of the hypothalamus, before being stored in the posterior pituitary. It acts on renal distal tubules and collecting ducts to increase water reabsorption by inducing increased expression of aquaporin-2 channels. • A decrease in osmolality causes the osmoreceptors to swell, suppressing ADH release, and results in increased excretion of water. – This diuresis peaks at about 90–120 minutes – Complete suppression of ADH secretion can result in excretion of 10–20 L of water a day • Non-osmotic triggers of ADH release are: – A 5–10% decrease in blood volume via carotid and aortic arch baroreceptors and possibly atrial stretch receptors – Pain, emotional stress, and hypoxia • Thirst mechanism. Osmoreceptors in the lateral preoptic area of the hypothalamus also respond to changes in extracellular osmolality, triggering thirst when osmolality increases and suppressing thirst when osmolality decreases. Thirst represents the major defense mechanism against hyperosmolality and hypernatremia, as it is the only response that increases water intake. However, the thirst mechanism is only functional in the conscious

patient.

DISEASE/PATHOPHYSIOLOGY

• Hyperosmolality (refers to the plasma osmolality): Usually, but not always, associated with hypernatremia. Water moves/shifts out of cells and into the vasculature in response. Clinical signs are predominantly neurologic. Lethargy, restlessness, and hyperreflexia can progress to coma, seizures, and death. Cerebral vein rupture leading to intracerebral or subarachnoid hemorrhage can result from rapid decreases in brain volume. Hyperosmolality is generally treated by correcting water deficits over a period of 48 hours with hypotonic solutions intravenously or increased oral water intake. • Diabetes insipidus (DI) is a defect in renal concentrating ability characterized by inappropriately dilute urine (<200 mOsm/kg) in the setting of an elevated serum osmolality (>295 mOsm/kg). Thus, polyuria, in the setting of hypernatremia or other indications of hyperosmolality, is seen. – Central DI results from a lack of ADH secretion from the hypothalamic–pituitary apparatus. It can result from a myriad of brain lesions, but is rare: Neurosurgical procedures such as transsphenoidal pituitary resection, traumatic or hypoxic brain injury, ruptured cerebral aneurysm, tumors, or inflammatory/infiltrative processes. Central DI can be diagnosed by an increase in urine osmolality after administering exogenous ADH in the form of desmopressin, also known as DDAVP. – Nephrogenic DI is characterized by normal ADH secretion, but failure of the kidneys to respond appropriately. The diagnosis is confirmed by administering exogenous ADH and subsequent production of dilute urine. Causes include congenital, drug-induced, and idiopathic etiologies; it can also be caused by hypercalcemia and hypokalemia. Treatment is geared towards correcting the underlying disorder and maintaining adequate water intake. Paradoxically, administration of a thiazide diuretic can decrease urine output by depleting total body Na+ and intravascular volume. More water is absorbed in the proximal tubules, and water delivery to distal tubules and collecting ducts is reduced. Protein and sodium restriction can also reduce urinary output. • Hypoosmolality (serum osmolality <260 mOsm/kg) always indicates excess TBW relative to body solutes or an excess water to solute ratio in the ECF. It is nearly always associated with hyponatremia. As with hyperosmolality, clinical symptoms of hypoosmolality are primarily neurologic with severity related to how quickly extracellular hypoosmolality develops. Rapid decreases in osmolality result in increased intracellular water, leading to brain edema and increased intracranial pressure. • Hyponatremia is the most common electrolyte abnormality encountered in clinical medicine. The majority of cases are chronic and asymptomatic. Patients with [Na+] >125 mEq/L are frequently asymptomatic. Early symptoms such as anorexia, nausea, and weakness are nonspecific. Progression of cerebral edema results in confusion, lethargy, seizures, coma, and ultimately death unless treated. Plasma sodium levels <120 mEq/L are associated with serious manifestations. • The syndrome of inappropriate ADH secretion (SIADH): The most common reason for acquired hyponatremia in hospitalized patients. A large variety of causes, including brain injury, critical illness, paraneoplastic syndromes, inflammation, pain, infections, and

medications (selective serotonin reuptake inhibitors, opiates, tricyclic antidepressants, diuretics, antineoplastic agents, antihypertensives, proton pump inhibitors). Characterized by excess ADH secretion, resulting in decreased plasma osmolality (<275 mOsm/kg) and inappropriately concentrated urine (>100 mOsm/kg). Patients are euvolemic and have normal acid–base balance. Typically, it is a diagnosis of exclusion. • Adrenal insufficiency can lead to increased ADH secretion from both non-osmotic stimulation secondary to decreased BP, and increased adrenocorticotropic hormone levels. • Hyperglycemia can result in [Na+]plasma decreases of ∼1 mEq/L for every 62 mg/dL increase in glucose concentration. • An osmolal gap is the discrepancy between measured and calculated osmolality; it indicates the presence of abnormal osmotically active substances). It can be seen in the following conditions: – Methanol, ethanol, isopropyl alcohol, or ethylene glycol intoxication – IV mannitol therapy – Chronic renal failure – Ketoacidosis – Patients absorbing large amounts of glycine or sorbitol containing irrigants – Marked hyperlipidemia or hyperproteinemia

PERIOPERATIVE RELEVANCE

• Hypernatremia and anesthetics: – If associated with hypovolemia, hypotension and tissue hypoperfusion can occur; vasodilation and cardiac depressant effects of anesthetic agents are accentuated. Decreased volume of distribution requires reducing most IV drug doses, whereas decreased cardiac output speeds up the onset of inhalational agents. – Increases MAC values of inhaled agents – Significant hypernatremia ([Na+] >150 mEq/L) should result in postponement of elective procedures until fluid deficits are corrected and underlying causes established. • A classic triphasic response to surgical or traumatic injury to the neurohypophysis consists of early central DI symptoms (<24 hours). This lasts for 3–5 days, followed by a period of hyponatremia resulting from the release of stored pituitary ADH. A week or more after the injury, the patient may experience permanent central DI, as the pituitary stores of ADH are exhausted. • Hyponatremia is frequently a sign of a serious underlying condition requiring careful preoperative workup. [Na+] >130 mEq/L are generally considered safe for patients undergoing general anesthesia and should be corrected to this level prior to all elective procedures even if the patient is asymptomatic. Lower concentrations can result in clinically significant cerebral edema that can manifest intraoperatively as a decrease in MAC or postoperatively as somnolence, agitation, or confusion. • Patients undergoing transurethral resection of the prostate, hysteroscopy, or other procedures can absorb large amounts (up to 20 mL/min) of water from irrigating fluids, placing them at risk of developing acute hypoosmolality. • Hypoosmolality is treated by eliminating body water using diuretics or replacing the patient’s sodium deficit with saline solutions. Except in severe brain edema or known acute

cases, serum [Na+] should not be corrected more than 10 mEq/L in the first 24 hours, and not more than 18 mEq/L in 48 hours. Rapid correction has been associated with demyelinating lesions in the pons known as central pontine myelinolysis (CPM) resulting in irreversible neurologic injury.

EQUATIONS

• TBW in liters can be estimated: – 0.5 × weight (kg) for women – 0.6 × weight (kg) for men • Plasma osmolality can be estimated:

Osmolality (mOsm/kg) ∼ 2 × [Na+]plasma(mEq/L)

– When elevated, glucose and urea contribute significantly to extracellular osmolality, therefore: • Saline solutions for the hyponatremic patient: 0.9% saline contains 154 mEq/L Na+ 3% saline contains 513 mEq/L Na+

REFERENCES

1. Bagshaw SM, Townsend DR, McDermid RC. Disorders of sodium and water balance in hospitalized patients. Can J Anesth. 2009; 56:151–167. 2. cAlister V, Burns KE, Znajda T, et al. Hypertonic saline for perioperative fluid management. Cochrane Database Syst Rev. 2010;20(1): CD005576.

ADDITIONAL READING

• Barash, Paul G, Cullen, et al. Clinical Anesthesia. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009. • Brenner. Brenner and Rector’s The Kidney, 8th ed. Saunders, 2007. • McPherson RA, Pincus MR. Henry’s clinical diagnosis and management by laboratory methods, 21st ed. Philadelphia, PA: W.B. Saunders, 2006 • Morgan GE, Mikhail MS, Maged S, et al. Clinical Anesthesiology. 4th ed. New York: Lange/McGraw-Hill, 2006.

See Also (Topic, Algorithm, Electronic Media Element) • Syndrome of inappropriate antidiuretic hormone • Diabetes insipidus • Hyponatremia • Hypernatremia • Extracellular fluid • TURP syndrome

CLINICAL PEARLS • Serum [Na+] can be used as a quick estimate of plasma osmolality under normal conditions.

• While abnormal osmolality and [Na+] are common, they can be a sign of serious problems. • Rapid changes in osmolality from administration of hyperosmolal or hypoosmolal fluids should be avoided.

PLATELETS

Yun Rose Li, BS Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Platelets are small cellular fragments that function to promote hemostasis and coagulation upon endothelial cell injury. • Minor platelet deficiencies usually present as bleeding of mucous membranes, petechiae, and epistaxis; large deficiencies can lead to life-threatening spontaneous hemorrhage. • Preoperative platelet counts are not typically checked unless there are clinical signs of coagulopathy. • A low platelet count is a poor indicator of platelet function. • Tests such as thromboelastograms measure clotting kinetics and aid with assessing function.

PHYSIOLOGY PRINCIPLES

• Platelets are small, irregularly shaped cell fragments that lack nuclei. Following endothelial cell injury, subendothelial collagen, von Willebrand factor (vWF), and tissue factor (TF) are exposed and activate the circulating platelets that they contact. Platelet clumping occurs and the coagulation cascade is activated to strengthen the clot. • Normal values for endogenous platelets: – Range: 150,000–400,000/μL – Production: ∼1 × 1011 produced daily – Survival: ∼9–10 days • Platelet donation – Pooled platelets: Centrifugation separates plasma and red blood cells from platelets. One platelet concentrate is attained via a “hard spin,” followed by a “soft spin” (or vice versa) of a whole blood unit (450 mL). The term “pooled” describes combining concentrates; however, it increases recipient exposure to HLA and infection (usually 6 different donor concentrates to comprise 1 jumbo unit). – Plasmapheresis: Extracorporeal collection of blood followed by separation and removal of platelets from red blood cells and plasma; the red blood cells and plasma are returned to the donor. The process lasts ∼90 minutes, and yields a single or double plateletpheresis unit (equivalent to 1 or 2 jumbo units of pooled platelets, respectively). The main benefit is the decreased exposure to multiple donors. Today, ∼80% of the US platelet supply comes in this manner. • Platelet storage – May be stored for up to ∼5 days at room temperature. – Unlike other blood products, cannot be cooled to slow down metabolism or reduce bacterial growth; platelet function is temperature sensitive. Temperatures <18°C damage micro-canalicular structures, and induce clustering of platelet receptors. In the recipient’s

circulation, macrophages will rapidly remove these previously “chilled” platelets. – Need to be continuously agitated to reduce bacterial growth – Special plastic containers are used to increase the surface-to-volume ratio and allow sufficient gas exchange between the internal volume and external ambient air (hypoxia is detrimental to survival, and metabolism is not slowed as with other transfusion units that can be cooled) • Platelet transfusion (1,2) – Cross-matching the recipient’s platelets with those of the donor is unnecessary; however, incompatibility can reduce post-transfusion counts. Platelets possess ABO antigens on their surface and RBCs are present in small amounts (<0.5 mL); when several units are needed, incompatible RBCs may cause hemolysis. Conversely, Type A and B antibodies from the donor’s plasma portion may react against the recipient’s RBCs when large volumes are administered. If several units are needed, ABO matching is prudent. – Rh antigens are not present on the platelet surface; however, RBCs (<0.5 mL) contained in the concentrate may lead to Rh immunization. Avoid incompatibility in women of childbearing years; if unavoidable, Rh Ig should be considered to prevent alloimmunization. • Normal values for transfused platelets – Range: “Platelet concentrate” is the term used for the platelets separated from 1 unit of WB. At most institutions, 6 platelet concentrates = 1 jumbo pack, or ∼3 × 1011 platelets. Plateletpheresis donors donate a “single” or “double” unit in a sitting. A single unit or 1 plateletpheresis unit = 3 × 1011 platelets; this is equivalent to 1 jumbo pack or 6 units of platelet concentrate. – Survival: ∼1–7 days post-transfusion. At day 5, intravascular recovery is ∼51%.

ANATOMY

• Platelets are produced by invaginations from the surface of megakaryocytes in the marrow of trabecular bone. • Inactive platelets circulate in the blood for ∼10 days as smooth, disk-shaped cells and are degraded via phagocytosis in the spleen and by Kupffer cells in the liver

DISEASE/PATHOPHYSIOLOGY

• Thrombocytopenia: A low platelet count can result from: – Increased destruction – Decreased production – Dilutional effects – Pseudothrombocytopenia • Thrombocytosis (thrombocythemia): Elevated platelet counts are due to: – Essential causes (e.g., myeloproliferative diseases) – Reactive causes (e.g., hyposplenism, splenectomy, acute phase reactant) – Iatrogenic causes • Infections – Storage of platelets at higher temperatures increases the risk of bacterial growth. – Frequently, infection is introduced by a needle entering the vein through nonsterile skin; it

can also occur, albeit rarely, from donor bacteremia or occult colon cancer. – Mortality from infection is high, particularly in immunocompromised patients with cancer or blood disorders. – Donor pathogens include HIV, HBV, HCV, CMV. • Febrile transfusion reactions: Secondary to leukocytes and soluble cytokines; may be avoided by transfusing leukocyte-reduced platelets. • Acute hemolytic reactions: Type A and B antibodies from the donor’s plasma may react against the recipient’s RBCs when large numbers of ABO-incompatible units are given. • Transfusion-associated graft versus host disease (TA-GVHD): Describes the abnormal immune response of T-lymphocytes attacking the host tissue; the risk is increased in immunocompromised patients. It is uniformly fatal, and there are minimal to no proven treatment options. Prevention consists of gamma-irradiating donor platelets prior to transfusions. • Transfusion related lung injury (TRALI): To reduce the incidence, storage may be performed in additive solutions instead of plasma.

PERIOPERATIVE RELEVANCE

• Quantitative: For most patients, a minimum of 50,000–100,000/μL is adequate to avoid bleeding during procedures and surgeries. See table for specific procedures and suggestions. • Qualitative: Platelet dysfunction and microvascular bleeding can occur despite adequate platelet counts. Uremia, aplastic anemia, chemotherapy, irradiation, ITP, and DIC can impair proper platelet function. Functional tests include the thromboelastogram (increased R time, decreased MA suggest platelet dysfunction). • Transfusion parameters – In a 70 kg patient, 1 × 1011 platelets increase platelet counts ∼10,000/μL. – 1 unit of pooled platelets (∼5–10 concentrates) contains ∼3 × 1011 and can increase recipient platelet counts by ∼30–60,000/μL. This is roughly equivalent to dosing 1 platelet concentrate/10kg – 1 plateletpheresis unit contains ∼3 × 1011 platelets, and can increase counts ∼30– 60,000/μL (equivalent to a jumbo unit of pooled platelets) • Transfusion considerations (2) – In children, consider ordering specific amounts from the blood bank to decrease waste (e.g., 20–25 mL). – “Volume reduce” by removing plasma to decrease the volume load in children or fluid overloaded patients (dialysis patients, congestive heart disease). However, this can result in a loss of 15–55% of platelets; alternatively, a smaller dose (with smaller volume) may be appropriate. – Inpatients or chronic conditions: Frequent transfusions of a lower dose of platelets may reduce the total amount of platelets needed, whereas larger doses extend the time needed between transfusions and may be more convenient. – Lack of response may be due to patient factors such as HLA antibodies, splenomegaly, DIC, amphotericin administration, and fever, as well as long storage time. Consider HLA matching, cross-matching, or “fresh platelets” (<48 hours after collection). – If donor-incompatible platelets are administered, consider washing or removing plasma

and resuspension with saline. This serves to decrease donor plasma antibodies and incompatible RBCs. • Massive transfusion/“damage control resuscitation." 1:1:1 transfusion of pRBC:FFP:platelets reduces risk of thrombocytopenia that can occur from the initial loss, followed by dilution from component therapy (FFP, PRBC devoid of platelets). • “Swirling” is a visual effect from diffraction when platelets are manually re-suspended and held up to a strong light. This indicates that the platelets are high quality and discoid and can be easily performed at bedside. Old platelets lack “swirling” and have a spherical morphology that lacks diffraction.

GRAPHS/FIGURES

Recommended platelet levels for procedures and surgeries: See Table

REFERENCES

1. McCullough J. Overview of platelet transfusion. Seminars in hematology. 2010;47(3):235– 242. 2. Stroncek DF, Rebulla P. Platelet transfusions. Lancet. 2007;370(9585):427–438.

ADDITIONAL READING

• Michelson AD. Platelets. 2nd ed. Academic Press, 2005. • Slichter SJ. Evidence-based platelet transfusion guidelines. Hematology. 2007;172–178.

See Also (Topic, Algorithm, Electronic Media Element) • Fresh frozen plasma • Thrombocytopenia • Transfusion related lung injury (TRALI) • Von Willebrand’s disease • Transfusion infection

CLINICAL PEARLS • Physiologic range = 150–400,000/μL; there are approximately 1 × 1011 newly produced platelets/day. For most patients, a minimum of 50–100,000/μL is adequate to avoid bleeding during procedures and surgeries. • Platelets are stored at a higher temperature than other transfusion products; they cannot be frozen, refrigerated, or infused through warmed tubing.

PNEUMONECTOMY Daniel Castillo, MD Sascha Beutler, MD, PhD

BASICS DESCRIPTION General

• Pneumonectomy describes the complete removal of the lung and can be performed for ipsilateral lymph node metastasis or when a lobectomy and its modifications are not sufficient to remove diseased tissue. • For open procedures (thoracotomy), exposure and dissection involves either rib spreading or removal of a portion of the rib. The pulmonary artery and veins are identified and stapled first, followed by the main bronchus; removal of the lung from the chest cavity occurs subsequently. An extrapleural pneumonectomy requires a more extensive resection of lymph nodes, pericardium, diaphragm, parietal pleura, and the chest wall. • The procedure may also be performed thoracoscopically (VATS). The smaller incision and reduced surgical stress (inflammatory mediators) may decrease postoperative pain and pulmonary dysfunction. Position

• Lateral decubitus with the operative side up. • A bean bag and axillary roll are often utilized.

Incision

• Posterior-lateral incision usually at the fifth or sixth intercostal space. • Median sternotomy approach has been described but is rarely performed today.

Approximate Time ∼2–3 hours

EBL Expected

<500 mL; re-do or extrapleural pneumonectomies can be significantly higher Hospital Stay

An average of 5–12 days

Special Equipment for Surgery

Arm boards and arm rest for lateral positioning EPIDEMIOLOGY Prevalence

Most commonly performed for lung carcinoma Prevalence

The prevalence of lung cancer is second to that of prostate cancer in men and breast cancer in women. Morbidity

• Postoperative pulmonary complications range from 11 to 49% (1)[B]. • Right pneumonectomy is associated with cardiac herniation. • Age > 65 years, right-sided procedures, and dysrhythmias were associated with an increased risk of a major complication (p < 0.05) (2)[B]. • Dysrhythmias increased the median length of stay from 8 to 11 days (p < 0.05). Age > 65 years, intrapericardial or extrapleural pneumonectomy, right-sided procedure, and any major complication are factors associated with an increased risk of dysrhythmias (p < 0.05) (2)[B]. • Others: Pulmonary embolism, myocardial infarction (MI), bronchopleural fistulas, chylothorax, subcutaneous emphysema, phrenic and recurrent laryngeal nerve injury.

Mortality

• Overall 30-day mortality ranges from 5–13% (5)[B]. • Increased with low predicted postoperative FEV1 (ppo-FEV1), high perfusion fraction of the resected lung (3)[B], and postoperative acute lung injury (30–50%) (4)[B].

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperative evaluation of lung and cardiac function along with discussion with the surgeon can help decrease factors leading to pulmonary complications. • One lung ventilation physiology and management • Judicious intraoperative fluid management can decrease acute lung injury (ALI).

PREOPERATIVE ASSESSMENT SYMPTOMS

Dyspnea, cough, hemoptysis History

• Extensive evaluation of pulmonary disease and cardiac status; exercise tolerance, cigarette smoking • Myasthenic syndrome (Eaton–Lambert)

Signs/Physical Exam

• Cyanosis, clubbing • Auscultation: Crackles, wheezes, distant sounds. • Pulmonary hypertension: Split or increased second sound • Heart failure: Peripheral edema, jugular venous distention, hepatomegaly

MEDICATIONS

• Radiation therapy and chemotherapy • Inhaled beta agonists, anticholinergics, or steroids • Antibiotics • Diuretics • Home oxygen • Antiarrhythmics

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• EKG – COPD: Right atrial and ventricular hypertrophy, low voltage QRS, and poor R wave progression across the precordial leads – Cor pulmonale: Enlarged P waves in lead II. • Arterial blood gas: Baseline hypoxia or CO2 retention • Imaging: Chest x-ray (CXR), CT scan, MRI to identify airway anatomy, masses, obstruction to flow and narrowing of airway, lung lesions/disease, lung hyperinflation, effusions, abscesses and hematomas • Pulmonary function tests: Performed to establish a baseline, to determine the ability to tolerate lung resection, and to risk stratify. • Split-lung function tests: Predicts the function of the lung tissue that will remain after resection CONCOMITANT ORGAN DYSFUNCTION

• Cardiac failure due to pulmonary disease • Right ventricular straining and hypertrophy • Arrhythmias • Hepatic congestion

TREATMENT PREOPERATIVE PREPARATION Premedications

• Minimize use of benzodiazepines and narcotics (may worsen hypercarbia). Benzodiazepines may contribute to postoperative delirium, especially in elderly patients. • Nebulizers: Beta agonists and anticholinergics.

Special Concerns for Informed Consent

• Possibility of prolonged postoperative intubation and mechanical ventilation • Blood and blood product transfusion • Invasive monitoring: Central line, arterial line, transesophageal echocardiography (TEE) • Regional anesthesia: Epidural, paravertebral blocks(6)[B]

Antibiotics/Common Organisms

Third generation cephalosporin for skin organisms INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia with thoracic epidural placement or ipsilateral paravertebral blocks with catheter placement for continuous infusion (6,7)[B]

Monitors

• Standard ASA monitors • Arterial line • Central line for CVP tracing and SvO2 monitoring • TEE

Induction/Airway Management

• Induction agent (often based on cardiac status) along with IV lidocaine, narcotics, and muscle relaxation are most commonly used. Introduction of volatile agent during bag mask ventilation will bronchodilate prior to laryngoscopy and intubation. • Double lumen tube (DLT), bronchial blocker, or main-stemmed single lumen tube. A fiberoptic scope is used to confirm proper placement.

Maintenance

• Ventilation – During OLV, implement an FiO2 of 1.0, low tidal volumes 5–6 mL/kg, and limit peak and plateau pressures to <35 and 25 cm H2O, respectively (8)[A].

– In the event of hypoxia, reassess tube position with FOB, if surgically possible proceed with brief manual bilateral lung ventilation, if not possible implement CPAP to the nondependent lung, followed by PEEP to the dependent lung, and consider pulmonary artery clamping. – ABGs should be performed intermittently or for intraoperative events to assess PaO2, PaCO2

• Fluids: A fluid restrictive technique has been shown to decrease the risk of ALI; however, it must be balanced with preserving renal funciton. It may be necessary to implement inotropes and vasoactive drugs to maintain adequate perfusion pressure and hemodynamic stability. Blood products should be administered in accordance with blood loss. • Renal: Maintain adequate perfusion pressures and a urine output of 0.5 mL/kg/hr. • Hemodynamics: Monitor cardiac function through TEE, CVP for right ventricle straining and failure, especially after pulmonary artery occlusion. • Analgesia: IV narcotics should be limited if a regional epidural catheter has been placed. Medication administration through the epidural catheter is usually initiated toward the end of the procedure once the chance of acute blood loss and unexpected hypotension is low. Extubation/Emergence

• Following repositioning, the heart can herniate into the empty right chest causing severe hemodynamic changes. The patient should be immediately repositioned in the left lateral decubitus and the surgeon should evaluate. A CXR can reveal if there is rapid filling of the empty chest and if drainage is necessary to balance the mediastinum. • If the patient is left intubated, the DLT needs to be exchanged for a single lumen. Sedation with propofol, dexmedetomidine, midazolam, or fentanyl should be started for transport to the ICU.

FOLLOW-UP BED ACUITY

ICU for a few days, followed by a step-down unit or floor. ANALGESIA

• Analgesia through a paravertebral or epidural catheter should be started or continued (6) [B], (7)[B]. Aids with deep inspiratory maneuvers and tolerance of respiratory rehabilitation. Studies have shown decreased postoperative complications. (7)[B]. • IV narcotics can be used if regional analgesia is not in place.

COMPLICATIONS

• Postoperative bleeding • Mediastinal shifting • Reintubation after inadvertent extubation can be catastrophic if the ETT is pushed through the bronchial stump • Arrhythmias usually after 48–72 hours postoperatively • Injuries related to the lateral decubitus position • Pulmonary edema, pulmonary embolism

PROGNOSIS

• High risk patients (9,10,11)[B]: – PaCO2 >46 mm Hg

– PaO2 <60 mm Hg (FiO2 of 21%) – FVC <50% or <1.5 mL/kg – FEV1 <50%

– Vital capacity <2 L – MVV <50% or 50 L/minute – RV/TLC <50% – DLCO <50% – Predicted post-resection FEV1 <800 mL

– Blood flow to the resected lung >70% – VO2max <10 mL/kg/min

• Pulmonary complications increase the morbidity and mortality rate by 35% (1)[B].

REFERENCES

1. lgar F, Alvarez A, Salvatierra A, et al. Predicting pulmonary complications after pneumonectomy for lung cancer. Eur J Cardiothorac Surg. 2003;23:201–208. 2. Harpole DH, Liptay MJ, DeCamp MM Jr, et al. Prospective analysis of pneumonectomy: Risk factors for major morbidity and cardiac dysrhythmias. Ann Thorac Surg. 1996;61:977–982.

3. Kim JB, Lee SW, Park SI, et al. Risk factor analysis for postoperative acute respiratory distress syndrome and early mortality after pneumonectomy: The predictive value of preoperative lung perfusion distribution. J Thorac Cardiovasc Surg. 2010;140:26–31.

4. icker M, de Perrot M, Spiliopoulos A, et al. Risk factors for acute lung injury after thoracic surgery for lung cancer. Anesth Analg. 2003;97:1558–1565.

5. Ramnath N, Demmy TL, Antun A, et al. Pneumonectomy for bronchogenic carcinoma: Analysis of factors predicting survival. Ann Thorac Surg. 2007;83(5):1831–1836. 6. Richardson J, Sabanathan S, Jones J, et al. A prospective, randomized comparison of preoperative and continuous balanced epidural or paravertebral bupivacaine on postthoracotomy pain, pulmonary function and stress responses. Br J Anaesth. 1999;83(3):387– 392. 7. Powell ES, Cook D, Pearce AC, et al. A prospective, multicentre, observational cohort study of analgesia and outcome after pneumonectomy. Br J Anaesth. 2011;106(3):364–370. 8. Schilling T, Kozian A, Huth C, et al. The pulmonary immune effect of mechanical ventilation in patients undergoing thoracic surgery. Anesth Analg. 2005;101:957–965. 9. Smetanta GW.Preoperative pulmonary evaluation: Identifying and reducing risks for pulmonary complications. Cleve Clin J Med. 2006;73(Suppl 1):S36–S41.Slinger P, et al.Preoperative evaluation of the thoracic surgery patient. Semin Anesth. 2002;21:168. 10. Nakahara K, Ohno K, Hashimoto J, et al. Prediction of postoperative respiratory failure in patients undergoing lung resection for cancer. Ann Thorac Surg. 1988;46:549–552. See Also (Topic, Algorithm, Electronic Media Element) • One lung ventilation • Video-assisted thoracoscopic surgery (VATS) • Bronchoscopy • Myasthenic syndrome • Postoperative pulmonary complications • Double lumen tube

CLINICAL PEARLS

• Optimal analgesia is key in postoperative management and outcome of thoracic surgery (6) [B], (7)[B]. • Pulmonary complications carry a significantly increased risk of mortality in postpneumonectomy patients.

PNEUMOTHORAX Moustafa Ahmed, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Pneumothorax describes the leaking and trapping of air or gas in the pleural space between the visceral and parietal pleura. The abolishment of the negative pleural pressure can result in intrapulmonary shunting, lung collapse, and hemodynamic embarrassment. • Definitions (1,2): – Non-communicating: The chest wall is intact or closed. – Communicating: The chest wall is open and air from the atmosphere directly enters the pleural space. – Tension: Results from the presence of a one-way valve where air enters and cannot leave, causing compression and displacement of mediastinal structures. – Primary spontaneous: Occurs without underlying disease. – Secondary spontaneous: Occurs as a result of underlying lung disease. – Traumatic: Accidents or iatrogenic • Perioperatively, patients with pneumothorax most often present: – Following a trauma – Iatrogenically from central line placement, brachial plexus blocks, barotrauma, or the surgical procedure – With a pre-existing diagnosis and a chest tube in situ EPIDEMIOLOGY Prevalence

• More than 20,000 new cases of spontaneous pneumothorax each year in the US (3). – Primary spontaneous pneumothorax (PSP) comprises ∼55% of cases – Secondary spontaneous pneumothorax (SSP) comprises ∼45% of cases • Of brachial plexus blocks, the supraclavicular approach has the highest incidence and ranges from 0.5–6% and diminishes with using ultrasound-guided nerve block.

Prevalence

• The recurrence rate of PSP is 28% and SSP is 43%. It typically occurs within 6 months–3 years (3). • Male > female

Morbidity

New cases cost the health system around $130,000,000.00 annually Mortality

• SSP is associated with a higher morbidity and mortality than PSP. • Death is secondary to respiratory and/or cardiac arrest.

ETIOLOGY/RISK FACTORS

• PSP occurs without underlying lung disease. – Tall, thin males, 10–30 years old – Smokers – Congenital disorders such as Marfan’s syndrome and familial pneumothorax – Change in atmospheric pressure or emotional changes – Pregnancy • SSP occurs in patients with underlying lung disease (1). – Airway disease: Chronic obstructive pulmonary disease, asthma, cystic fibrosis – Infectious lung disease: Tuberculosis, pneumoconioses, necrotizing pneumonia, pneumocystis carinii pneumonia – Idiopathic pulmonary fibrosis: Sarcoidosis, histiocytosis X – Connective-tissue disease: Rheumatoid arthritis, ankylosing spondylitis, polymyositis/dermatomyositis, scleroderma, Marfan’s syndrome, Ehlers–Danlos syndrome – Cancer: Lung cancer, sarcoma • Traumatic pneumothorax – Accidental: Penetrating, non-penetrating, rib fracture, diving, flying – Iatrogenic: During invasive diagnostic and supportive modalities like transbronchial biopsies, thoracentesis, mechanical ventilation, pleural biopsy, central venous access, brachial plexus blocks

PHYSIOLOGY/PATHOPHYSIOLOGY

• The thoracic space is comprised of (going from out to in): – Chest wall: Rigid, with outward expanding properties – Parietal pleura: Layer of tissue that is attached to the inner surface of the rib cage and moves in conjunction with the ribs. – Intrapleural space: A potential space that is under negative pressure and contains a small amount of fluid (provides lubrication and aids with movement). Maintains a “connection” between the chest wall and lungs (via the pleura), allowing them to move in conjunction with one another – Visceral pleura: Layer of tissue that covers the lungs, blood vessels, and bronchi – Lungs: Soft tissue without rigidity, and a tendency to collapse inward. • Leaking or trapping of air in the pleural sac can lead to a loss of negative intrapleural pressure with resultant lung collapse and outward chest wall movement. This can result in: – Intrapulmonary shunting secondary to atelectasis (perfusion without ventilation) – Decreased pulmonary compliance from decreased lung volumes. Manifests as increased peak and mean pressures – Tension pneumothorax if a one-way valve traps air within the intrapleural space with each inspiration. Pressure develops and accumulates without a means to escape and can cause compression and displacement of mediastinal structures (heart, great vessels). Severe hypotension or cardiac arrest as well as hypoxia and respiratory arrest can occur.

PREVENTATIVE MEASURES

• Ventilator settings should be adjusted to decrease peak and mean pressures • For subclavian line placement – Consider ultrasound guidance – In mechanically ventilated patients, decrease tidal volumes; in awake, spontaneously ventilated patients, ask the patient to hold their breath after exhaling. – Utilize a shallow angle for needle insertion – Minimize the number of attempts and consider alternate sites, if appropriate • For brachial plexus blocks, consider ultrasound guidance, in particular with supraclavicular blocks • Prior to sternotomy, hold inspiration

PREOPERATIVE ASSESSMENT • Intraoperatively – History: Trauma patients; recent central line placement or brachial plexus block; high peak or mean pressures needed to mechanically ventilate the patient; recent surgical events; smokers; tall thin males; and underlying pulmonary disease – Symptoms: Dependent upon the size and speed by which it occurs. In awake patients, sudden onset of chest pain associated with shortness of breath, coughing. – Physical examination General: Hypoxia, cyanosis, tachycardia, hypotension Chest: Rapid shallow breathing, dyspnea, deviation of the trachea, limited chest wall motion, distended neck veins; asymmetry of chest wall expansion; hyper-resonance; diminished or absent breath sounds on the side of the pneumothorax, absent egophony and bronchophony Beck’s triad: Hypotension, jugular venous distention, and muffled heart tones – Arterial blood gas: PaO2 decreased, Alveolar- arterial (A-a) gradient increased (a/A ratio decreased). – Chest radiography can confirm the diagnosis as well as provide information on the size and location. It should be performed during inspiration to yield the best results. However, in the event of hemodynamic instability and high suspicion of a pneumothorax, it should not delay needle decompression (1). Non-tension: The visceral pleura is separated from the parietal pleura and appears as a white line with no lung or vascular markings adjacent to the chest wall. Tension: Lung tissue has collapsed and “hugs" the heart; there is a “black-out" of a large portion of the affected lung site (air); and mediastinal structures are shifted away from the affected lung. – Ultrasound scan: May be more readily available to perform. This technique is commonly used in trauma bays with the benefit of being fast and effective, and improving earlier detection. It has a sensitivity of 95–100% (superior to CXR and comparable with CT scan) (4).

DIFFERENTIAL DIAGNOSIS

• Acute coronary syndrome • Aortic dissection • Esophageal spasm • Acute pericarditis • Pericardial tamponade • Pulmonary embolism • Pleural effusion • Pneumonia • Foreign body and airway obstruction • Esophageal perforation

TREATMENT • Management strategy is based on the degree of clinical compromise, and not necessarily the size of the pneumothorax. A chest tube, or tube thoracostomy, is performed to drain the air collection and allow for re-expansion of the lung. It is attached to a drainage system with three compartments (collection, water seal, and suction control chamber). A chest radiograph is performed to verify placement (2). • Tension pneumothorax management is a clinical emergency and requires (2): – Immediate needle decompression, by placing a 14 gauge angio-catheter in the second intercostal space at the midclavicular line. If the angio-catheter is not long enough or the patient has a thick chest wall, it is possible to use the fourth or the fifth interspace as an alternative site (the chest wall is not as deep at this space) – Placement of a chest tube.

FOLLOW-UP • Persistent air leak requires a thoracic surgery consult. Surgical management may be indicated for: – Persistent air leak more than 5–7 days with chest tube drainage or failure of lung reexpansion – Spontaneous hemothorax – Professions at risk (pilot, divers) – Pregnancy – Synchronous bilateral spontaneous pneumothorax – First contralateral pneumothorax – Second ipsilateral pneumothorax • Chemical pleurodesis may be indicated when the patient is not a candidate for surgery, or refuses surgical intervention (high rate of recurrence). It involves the insulation of sclerosant into the pleural space that induces aseptic inflammation with resultant adhesion of the parietal and visceral pleura. Agents include tetracycline, minocycline, talc, and doxycycline. • Air travel should be avoided until full resolution. • Diving should be permanently avoided unless instructed to do so.

CLOSED CLAIMS DATA Not available

REFERENCES

1. acDuff A, Arnold A, Harvey J. Management of spontaneous pneumothorax: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010;65(Suppl 2):ii18–ii31. Warakaulle DR, Trail ZC. Imaging of pleural disease. Imaging. 2004;16(4):10–21. 2. Wakai A, O’Sullivan RG, McCabe G. Simple aspiration versus intercostals tube drainage for primary spontaneous pneumothorax in adults. Cochrane Database Syst Rev. 2007:CD004479. 3. Lyon M, Walton P, Bhalla V, et al. Ultrasound detection of the sliding lung sign by prehospital critical care providers. Am Emerg Med. 2012; 30(3):485–488. 4. Baumann MH, Strange C, Heffner JE, et al. AACP Pneumothorax Consensus Group. Management of spontaneous pneumothorax: An American College of Chest Physicians Delphi consensus statement. Chest. 2001;119(2):590–602. See Also (Topic, Algorithm, Electronic Media Element) • Chest tubes • Trauma • Video-assisted thoracoscopic surgery (VATS)

CODES ICD9 • 512.0 Spontaneous tension pneumothorax • 512.81 Primary spontaneous pneumothorax • 512.89 Other pneumothorax ICD10 • J93.0 Spontaneous tension pneumothorax • J93.9 Pneumothorax, unspecified • J93.11 Primary spontaneous pneumothorax

CLINICAL PEARLS

• Patients with chest tubes in situ may present for surgical procedures. The anaesthetist should identify the cause, size of the pneumothorax, and current chest tube management. • Avoid nitrous oxide in trauma patients, as a pneumothorax may be present but not identified. In addition, maintain a high degree of suspicion for the development of Beck’s triad, or increases in peak and mean pressures in this patient population.

POLYCYTHEMIA Keyuri Popat, MD

BASICS DESCRIPTION

• Polycythemia is Greek for “too many cells in the blood.” Also known as erythrocytosis, it describes the elevation of the hematocrit either from an increase in red blood cell mass (absolute) or decrease in plasma volume (relative). • Polycythemia vera (PCV) is a myeloproliferative disorder that is often accompanied by dysfunctional platelets and an increase in white blood cells. • Secondary polycythemia is the body’s compensatory or physiologic response to chronic hypoxia. • Polycythemia can increased blood viscosity and the risk of thrombosis.

EPIDEMIOLOGY Prevalence

Polycythemia vera: 1.9/100,000 people Prevalence

Higher in males aged 70–79 years Morbidity

Arterial ischemic complications occur in 24–43% of patients Mortality

Median survival of patients with untreated PCV is 6–18 months from the time of diagnosis. The main causes of death are thrombosis and disease transformation into myelofibrosis with myeloid metaplasia (MMM) and/or acute myeloid leukemia. Survival of treated patients exceeds 10 years. ETIOLOGY/RISK FACTORS

• Primary polycythemia results from increased sensitivity of erythroid progenitors to regulatory growth factors; most commonly PCV. • Secondary polycythemia or physiologic polycythemia – Chronic hypoxia from chronic obstructive pulmonary disease, obstructive sleep apnea (OSA), or Pickwickian syndrome – Elevated altitude – Cyanotic heart disease – Increased erythropoiesis from exogenous erythropoietin or erythropoietin-secreting tumors – Endocrine disorders such as Cushing’s syndrome • Relative polycythemia can result from a decrease in plasma volume. Causes include

insensible fluid losses, diarrhea, sweating, fever, or phlebotomy

PHYSIOLOGY/PATHOPHYSIOLOGY

• PCV is a chronic myeloproliferative disorder that is characterized by erythroid proliferation and secondary platelet proliferation. PCV can progress from a proliferative stage to a metastatic phase and develop into a malignant phase. Treatment revolves around controlling excessive production of erythrocytes or platelets. However, the clinical course of PCV can be complicated by a variety of events, such as: – Bleeding due to poor quality of platelets despite normal or high numbers, as well as acquired von Willebrand’s disease (likely due to increased binding of large vWF multimers to the platelets and their removal from the plasma). Cytoreduction with drugs such as hydroxyurea corrects the clinical and lab value. Desmopressin can also be used for treatment. – Thrombosis can result from the increased viscosity of blood. Fatal thrombotic complications include myocardial infarction. Low dose aspirin is helpful • Secondary polycythemia is a physiologic, compensatory response to chronic hypoxia by stimulating erythropoietin. In turn, erythropoietin stimulates red blood cell production to increase the oxygen carrying capacity and delivery to tissues. – Smoking: Carbon monoxide (CO) results in decreased levels of oxyhemoglobin; CO has a 300-fold increased affinity to hemoglobin compared to oxygen. In addition, carboxyhemoglobin has impaired oxygen offloading at peripheral tissues. – OSA – High altitude – Endocrine disorders: Patients with JAK2 mutation also have hypercortisolism – Congenital heart disease: Cyanotic heart disease results in increased pulmonary vascular resistance as well as sustained hypoxia. The body may respond with increased erythropoietin levels. • Increased blood viscosity can result in: – Increased myocardial wall tension. LaPlace’s law states that tension is directly proportional to myocardial chamber radius and intraventricular pressures, and indirectly related to myocardial wall thickness. Viscosity is a determinant of intraventricular pressure (e.g., a bag filled with air would require less tension to empty than if filled with water or a thick, gel-like substance). – Decreased blood flow secondary to thrombosis – Decreased blood flow secondary to increased vessel wall resistance

ANESTHETIC GOALS/GUIDING PRINCIPLES

• For PCV, the severity of disease needs to be assessed; consider a hematology consult to determine the need for phlebotomy, hemodilution, thromboprophylaxis, and prevention of hemorrhage. • Since secondary polycythemia is an indicator of chronic hypoxic disease, the underlying pathology should be assessed. In patients with COPD, a careful history and examination should be made to identify exacerbations or infection.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Headache • Weakness • Pruritus due to mast cell degranulation, with release of histamine • Burning pain in hands and feet due to microvascular thrombotic • Epistaxis

History

• Headaches • Excessive sweating • Exposure to, or residence in, high altitudes

Signs/Physical Exam

• Thrombosis • Splenomegaly due to platelet sequestration • Hepatomegaly • Gouty arthritis increased uric acid due to cell breakdown

TREATMENT HISTORY

• Phlebotomy involves bleeding the patient down to a decreased hematocrit. This is usually done in conjunction with aspirin and maybe chlorambucil or hydroxyurea • Oxygen therapy may aid with decreasing erythrocytosis in patients with secondary polycythemia (e.g., chronic obstructive pulmonary disease).

MEDICATIONS

• Hydroxyurea • Aspirin • Chlorambucil • Interferon alpha • Secondary polycythemia from pulmonary disease. Patients may be on bronchodilators, inhaled or oral steroids, or antibiotics.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hemoglobin/hematocrit • Red blood cell volume • White blood cell count • Platelets: Patients can have concurrent thrombocytosis. • Coagulation profile; abnormalities should prompt testing for von Willebrand’s disease. • Urinalysis: Hematuria may be the only clue to the presence of erythropoietin-secreting renal cell carcinoma • Chest radiography

• JAK2 mutation on blood work • Bone marrow biopsy will show an increased number of megakaryocytes in a moderately to markedly hypercellular marrow.

CONCOMITANT ORGAN DYSFUNCTION

• Peptic ulcer disease • Renal failure • Organ dysfunction due to thrombosis (myocardial infarction, cerebrovascular accident, deep venous thrombosis, pulmonary embolism)

CIRCUMSTANCES TO DELAY/CONDITIONS

• Acute thrombosis as evidenced by acute myocardial ischemia or acute ischemic stroke • Pulmonary disease exacerbation (e.g., COPD)

CLASSIFICATIONS

• Primary polycythemia • Secondary polycythemia • Relative polycythemia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Hydration • Phlebotomy and hemodilution • Thromboprophylaxis with sequential compression devices, antiplatelets, anticoagulants

INTRAOPERATIVE CARE Choice of Anesthesia

• Depends upon the surgical procedure and patient preference • Neuraxial blocks may be contraindicated depending upon the thromboprophylaxis chosen, as well as platelet dysfunction. Monitors

• ASA standard monitors • Consider an arterial line for frequent intraoperative labs • Foley catheters may be placed when hemodilution needs to be performed, or in cases that are long or have large fluid shifts Induction/Airway Management

• Airway instrumentation should be performed with care, as platelet dysfunction can result in bleeding • In patients with pulmonary disease, avoid bronchospasm by ensuring an adequate depth of anesthetic and muscle relaxation prior to airway instrumentation

Maintenance

• Fluid hydration: Maintain adequate hemodynamics and urine output. The monitors would depend on the type of surgery and any other co-morbidities. • In patients with pulmonary disease, maintain an adequate depth of anesthesia to avoid bronchospasm. • Acquired von Willebrand’s disease can result in increased intraoperative bleeding.

Extubation/Emergence

• Avoid airway trauma • In patients with pulmonary disease, consider deep extubation or other maneuvers to avoid coughing, bucking, or bronchospasm

FOLLOW-UP BED ACUITY

Standard postoperative care

MEDICATIONS/LAB STUDIES/CONSULTS

Hematology consult may be considered as appropriate COMPLICATIONS

• Thrombosis including myocardial infarction, cerebrovascular thrombosis, deep vein thrombosis, pulmonary embolism • Bleeding from dysfunctional platelets or disseminated intravascular coagulation

REFERENCES

1. Logan MS, Watson CM, Nottingham JM. Symptomatic splenomegaly in polycythemia vera: A review of the indications for splenectomy and perioperative considerations. Am Surg. 2009;75(5):363–368. 2. Landolfi R, Di Gennaro L. Thrombosis in myeloproliferative and myelodysplastic syndromes. Hematology. 2012;17(Suppl 1):S174–176. 3. Barosi G, Lupo L, Rosti V. Management of myeloproliferative neoplasms: From academic guidelines to clinical practice. Curr Hematol Malig Rep. 2012;7(1):50–56. 4. Passamonti F. How to manage polycythemia vera. Leukemia. 2012;26(5):870–874. 5. Kent BD, Mitchell PD. McNicholas WT. Hypoxemia in patients with COPD: Cause, effects, and disease progression. Int J Chron Obstruct Pulmon Dis. 2011;6:199–208. See Also (Topic, Algorithm, Electronic Media Element) • Obesity hypoventilation syndrome • Chronic bronchitis • Smoking

CODES ICD9

• 238.4 Polycythemia vera • 289.0 Polycythemia, secondary • 289.6 Familial polycythemia ICD10 • D45 Polycythemia vera • D75.0 Familial erythrocytosis • D75.1 Secondary polycythemia

CLINICAL PEARLS

• Spurious polycythemia should be assessed in light of overall volume status; hemoconcentration should first be ruled out.

POSITIVE END EXPIRATORY PRESSURE (PEEP) Justin C. Shields, MD Andrea Vanucci, MD, DEAA

BASICS DESCRIPTION

• Positive end expiratory pressure (PEEP) is the supra-atmospheric pressure present in the alveoli at the end of expiration. • During mechanical ventilation, PEEP is generated by valves incorporated into the ventilator or externally applied to the expiratory side of the respiratory circuit. • PEEP has effects on the pulmonary and cardiovascular systems. – Pulmonary: Increases functional residual capacity (FRC) by preventing collapse and contributes to the re-opening of distal airways and alveoli; optimizes ventilation and hence V/Q matching. – Cardiac: Decreases venous return to the heart, and diminishes cardiac output. This effect is more pronounced in patients with normal lung compliance and/or hypovolemia. – “Best PEEP” is the level of end expiratory pressure required to produce maximal oxygen transport, while maintaining an adequate cardiac output necessary to deliver the arterial oxygen to the peripheral tissues. It represents the point of equilibrium between the effects on the respiratory and cardio-circulatory system. PHYSIOLOGY PRINCIPLES

• “Physiologic PEEP” is present in all spontaneously breathing subjects and is produced by narrowing of the glottis during exhalation. Physiologic PEEP is estimated to be around 3–5 cm H2O.

• “Extrinsic PEEP” is applied to the airways of patients on ventilator support with the goal of improving oxygenation and respiratory mechanics. Clinicians may select different levels of PEEP depending on a patient’s clinical condition, and the respiratory and hemodynamic response to the initial setting. • PEEP’s effects on respiratory function: – Stabilizes lung parenchyma by maintaining the patency of distal airways and alveoli especially in the dependent areas of the lung that tend to collapse in patients under general anesthesia. Patent alveoli can be ventilated and participate in oxygenation of pulmonary blood (V/Q matching). This is manifested as an increase in SpO2, PaO2, and

decrease in intrapulmonary shunt fraction. – Increases FRC by contributing to the re-opening of collapsed alveoli – Prevents cyclic opening and closing of alveoli during the respiratory cycle. This repeated opening and closing has been associated with alveolar damage and the systemic release of inflammatory mediators. Theoretically, they can contribute to the development of multiorgan failure.

– Extrinsic PEEP may decrease work of breathing in patients with airway flow limitation on partial respiratory support. – Overdistension is associated with decreased lung compliance and increased dead space ventilation. • PEEP’s effects on cardiovascular function: – Increases mean airway pressure that gets partially transmitted to the heart and increases the transmural pressure. As a result, this can compromise venous return to the right atrium, and reduce cardiac output. On the contrary, in patients with reduced left ventricle function, PEEP decreases the relative afterload of the LV. LV dysfunction can result in decreased pulmonary volume and compliance. As a result, greater (more negative) inspiratory pressures, and hence transmural pressures, are required to maintain tidal volumes. The addition of PEEP can partially offset this. – Alveolar overdistension results in compression of alveolar capillaries and increased pulmonary vascular resistance; this results in increased right ventricular afterload and can impair right ventricular output. • PEEP’s effects on neurologic function: – Levels >10 cm H2O may increase intracranial pressure (ICP) by impeding venous drainage from the brain. Thus, in patients with increased ICP, judicious PEEP titration is recommended, taking into consideration both changes in oxygen delivery to the brain and intracranial compliance. – PEEP use with the intent of maintaining positive pressure in the intracranial venous sinuses is a frequently reported practice. However, there is no conclusive evidence to suggest that PEEP alone is sufficient to prevent venous air embolism (VAE) in neurosurgical procedures. In addition, in patients with a patent foramen ovale, it can increase the mean intrathoracic pressures and theoretically favor the entry of an embolus into the left heart. • PEEP’s effects on renal function: – If PEEP compromises cardiac output, it can decrease renal perfusion and activate the renin–angiotensin–aldosterone system (RAAS). The RAAS causes an increase in solute and water reabsorption at the glomerular level, and reduced urinary output.

ANATOMY

PEEP exerts most of its direct effects at the level of the alveoli and distal bronchi. Atelectasis, however, occurs mostly in the dependent portions of the lungs during general anesthesia or with the use of neuromuscular blockade. PHYSIOLOGY/PATHOPHYSIOLOGY

• Atelectasis is considered a pre-inflammatory state, and can serve as a nidus for infection and contribute to pulmonary complications. • “Intrinsic PEEP”: Although the therapeutic effects of physiologic and extrinsic PEEP are often discussed, “intrinsic” PEEP (or auto-PEEP) should also be considered. Intrinsic PEEP is caused by alveolar air trapping secondary to incomplete breath exhalation. This incomplete expiration results in supra-atmospheric alveolar pressure and increased lung volume. There are 3 possible mechanisms leading to the development of intrinsic PEEP: – Dynamic hyperinflation, caused by large tidal volumes and high respiratory rate, which

does not allow full lung exhalation before the next breath starts. – Airway flow limitation, caused by `premature’ small airway collapse that is typical of patients with increased closing volumes (e.g., COPD). – Increased expiratory resistance, as seen with a kinked endotracheal tube, small diameter endotracheal tube, or airway obstruction by bronchial secretions. • Extrinsic and intrinsic PEEP can both contribute to barotrauma.

PERIOPERATIVE RELEVANCE

• Obesity: A greater degree of atelectasis occurs during general anesthesia in obese patients. Application of PEEP/CPAP by a face mask should begin prior to induction with the patient in reverse Trendelenburg position. During the case, PEEP at a level of 10 cm H2O combined with frequent recruitment maneuvers (40–60 cm H2O for 6–8 seconds) has been shown to

be effective. Continue PEEP until extubation and consider CPAP in the PACU. • Laparoscopic surgery decreases FRC and respiratory compliance by moving the diaphragm cephalad, and causing atelectasis. PEEP alone (at a level of 10 cm H2O) does not improve oxygenation; however, in combination with frequent recruitment maneuvers and beach chair positioning, PEEP has been shown to improve oxygenation, end expiratory lung volume, and respiratory compliance (3)[B].

Pediatric Considerations

• FRC decreases under general anesthesia and paralysis. In infants, who typically have very compliant chest walls, PEEP helps in maintaining the FRC, because it compensates for the prevailing tendency toward alveolar collapse that results from the interaction between the uneven and opposing forces generated by lung elastic recoil (favoring collapse) and by the smaller forces generated by the chest wall (promoting lung expansion). PEEP at levels of 3– 6 cm H2O has been shown to increase FRC in ventilated children without respiratory disease. Its effects on increasing FRC is more pronounced in children receiving 100% FiO2

(prevention of reabsorption atelectasis is the likely mechanism). Optimal intraoperative PEEP settings have not been clearly established for children, but likely vary depending on age, comorbidities, and body size. • One lung ventilation: Application of low to moderate levels of PEEP to the dependent lung can improve arterial oxygenation depending upon individual amounts of atelectasis, presence of intrinsic PEEP, and TV settings (4)[A]. PEEP usually improves oxygenation in patients who respond to recruitment maneuvers. Conversely, by increasing mean pressure in the dependent lung, it can shunt blood to the non-dependent and non-ventilated lung, worsening V/Q mismatch. • Prone positioning: Benefits are probably less pronounced, and optimal levels are likely lower than in the same subjects in the supine position. This is due to the different effects on the distribution of ventilation and perfusion as compared to supine subjects, leading to greater V/Q mismatch in prone patients (2)[B]. • COPD: These patients are prone to develop intrinsic PEEP and require personalized ventilator management; the I:E ratio should be adjusted to provide a longer expiratory time. A low respiratory rate is also recommended. The application of low levels of extrinsic PEEP

(less than intrinsic PEEP) in supported ventilator modes can help alleviate intrinsic PEEP by maintaining the peripheral bronchi open. In particular, during one lung ventilation, these patients tend to develop intrinsic PEEP. The application of extrinsic PEEP may worsen air trapping. • Asthma: Flow limitation and airway inflammation can result in intrinsic PEEP. Thus, as in COPD patients, low respiratory rates and adequate expiratory time should be established. PEEP in controlled, mechanical ventilation may lead to hyperinflation. Conversely, spontaneously breathing patients will have a reduced work of breathing with modest amounts of PEEP. • Acute respiratory distress syndrome (ARDS): PEEP increases oxygenation and improves respiratory mechanics by minimizing the amount of cyclic opening and closing of alveoli (associated with the systemic release of inflammatory markers and multiple organ dysfunction). Current evidence recommends the use of higher levels of PEEP for PaO2:FiO2 levels ≤200 mm Hg and lower levels of PEEP for PaO2:FiO2 between 201–300 mm Hg. It is

recommended that PEEP be increased with FiO2 in a stepwise fashion to maintain end

expiratory transpulmonary pressure (Ttp) between 0–10 cm H2O. Ttp can be calculated by

subtracting the esophageal pressure (a surrogate of pleural pressure) from airway pressure. Esophageal balloon catheters can be used to measure esophageal pressure (6)[B]. In patients with ARDS, an initial higher level of PEEP (>12 cm H2O) may confer a survival benefit

with respect to lower levels (7)[A]. • The typical initial setting of PEEP is 5 cm H2O; titration is usually up or down by 2–3 cm H2O while monitoring for changes in:

– Hemodynamics: Heart rate, BP, and urine output – Arterial line (if present): Changes in pulse pressure or stroke volume variation, possibly reversed by volume loading. – Oxygenation: Increases in SpO2 saturation and PaO2 on arterial blood gases.

– ETCO2: Increased values may suggest decreased intrapulmonary shunt or increased cardiac output (improved CO2 delivery for exhalation).

– Respiration mechanics: A reduced gradient between plateau pressure and end expiratory pressure suggests a PEEP-induced increase in lung recruitment shown by an increase in respiratory compliance. However, high PEEP can cause barotrauma such as pneumothorax or subcutaneous emphysema. Peak and airway pressures must be constantly monitored. – FiO2 titration: High FiO2 can result in absorption atelectasis; if possible, titrate FiO2

downward. – Intrinsic PEEP is suspected when the expiratory flow waveform fails to return to 0 at the end of expiration. – “Best PEEP”: Requires concurrent measurements of the cardiac output and PaO2.

• Outcome studies of PEEP during anesthesia: There is no sufficiently powered study to indicate any improvement in mortality or in pulmonary complications following the use of PEEP. There is, however, data indicating higher PaO2/FiO2 ratios on postoperative day 1 and less atelectasis by CT scan in patients who received PEEP during anesthesia (5)[A].

• Contraindications: PEEP should be avoided or used cautiously in patients with the following conditions: – Hypotension/hypovolemia – Increased ICP – Focal pneumonias: PEEP may cause overdistension of alveoli in the healthy lung, causing compression of their capillaries and leading to diversion of blood flow to the affected lung segments, causing hypoxemia. – Bronchopleural fistulas: PEEP may lead to overpressurization of the pleural cavity causing a tension pneumothorax. PEEP can also delay healing of a bronchopleural fistula (1)[A].

EQUATIONS

Lung compliance = Vt/(Ppl − PEEP); Vt = Tidal volume, Ppl = Plateau pressure

REFERENCES

1. Acosta P, Santisbon E, Varon J. The use of positive end-expiratory pressure in mechanical ventilation. Crit Care Clin. 2007;23:251–261. (A) 2. Petersson J, Ax M, Frey J, et al. Positive end-expiratory pressure redistributes regional blood flow and ventilation differently in supine and prone humans. Anesthesiology. 2010;113:1361–1369. (B) 3. Futier E, et al. Intraoperative recruitment maneuver reverses detrimental pneumoperitoneum-induced respiratory effects in healthy weight and obese patients undergoing laparoscopy. Anesthesiology. 2010;113:1310–1319. (B) 4. Karzai W, Schwarzkopf K. Hypoxemia during one-lung ventilation. Anesthesiology. 2009;110:1402–1411. (A) 5. Imberger G, McIlroy D, Pace NL, et al. Positive end-expiratory pressure (PEEP) during anesthesia for the prevention of mortality and postoperative pulmonary complications. Cochrane Database of Syst Rev. 2010;9. (A) 6. Talmor D, Sarge T, Malhotra A, et al. Mechanical ventilation guided by esophageal pressure in acute lung injury. NEJM. 2008;359:2095–2104. (B) 7. Briel M, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: Systematic review and meta-analysis. JAMA. 2010;303(9):865–873. (A) See Also (Topic, Algorithm, Electronic Media Element)

• Functional residual capacity • Acute respiratory distress syndrome • Laparoscopy

CLINICAL PEARLS

• In patients under general anesthesia, PEEP contributes to preventing end expiratory closure of airways and alveoli, which is the primary mechanism leading to shunt and hypoxemia in anesthetized and mechanically ventilated subjects.

• The application of PEEP must be carefully titrated while weighing the benefits of improved respiratory mechanics and arterial oxygenation against the risk of barotrauma and decreased cardiac output. • Intrinsic PEEP may increase inspiratory work of breathing in patients either breathing spontaneously, or on CPAP and PS modalities. The application of extrinsic PEEP at values less than the intrinsic PEEP (50–70% of intrinsic PEEP) may reduce the work of breathing.

POST-HEART TRANSPLANT Kalpana Tyagaraj, MD

BASICS DESCRIPTION

• Heart transplantation has become an established therapeutic modality for patients with endstage heart disease. • Refined transplantation techniques, improved patient selection, cyclosporine immunosuppression, improved monitoring and anesthetic management techniques as well as appropriate postoperative care have enhanced the survival rate of recipients. • Consequently, many more of these patients present for elective or emergency operations.

EPIDEMIOLOGY Prevalence

• US population: ∼2,000–2,500 heart transplants are performed annually. • The number of transplant surgeries is primarily limited by the availability of donors.

Prevalence

Familial idiopathic dilated cardiomyopathy: ∼20–40% Morbidity

See Concomitant Organ Dysfunction Mortality

Overall survival rate: 1 year 81%, 3 years 75%, 10 years 70% ETIOLOGY/RISK FACTORS

The two most common indications for transplantation are ischemic cardiomyopathy and idiopathic dilated cardiomyopathy. Together, they comprise 90% of all transplant recipients. PHYSIOLOGY/PATHOPHYSIOLOGY

• Denervated heart: The post-transplant heart retains normal Frank–Starling mechanisms, impulse formation and conductivity, as well as intact α and β receptors that respond to circulating catecholamines. However, it lacks normal responses and variations to respiration, carotid massage, and Valsalva maneuvers. The denervated heart has a faster basal resting heart rate, increased incidence of cardiac dysrhythmias, and a preloaddependent cardiac output. • Allograft rejection: Most episodes occur within the first 3 months with a peak at about 4–6 weeks. The pathogenesis involves cellular (lymphocyte infiltration) and/or humoral (antibody) mechanisms. The clinical spectrum of rejection includes fatigue, ventricular dysrhythmias, congestive heart failure, silent myocardial infarction, and sudden death.

Early diagnosis is by endocardial biopsy. The time course involves a hyperacute stage (first 24 hours after transplant), an acute stage (within 6–8 weeks), and a chronic stage (months to years after transplant). Treatment involves augmented steroid therapy. • Infection: Immunosuppressive agents should be continued indefinitely, making infection an ever-present risk. The leading cause is direct contact with contaminated material. Infections are most prevalent in the first few weeks after transplantation, and include mediastinitis and opportunistic infections (CMV, Pneumocystis carinii, toxoplasma, and Legionella). • Effects of immunosuppressive agents on anesthetic management: Cyclosporine enhances the effects of muscle relaxants. Thus, a prolonged blockade may be seen after vecuronium or pancuronium. • Effects of anesthetic management on immunosuppressive agents: Cyclosporine or tacrolimus levels must be kept within indicated therapeutic range. – Dilution with massive fluid infusion and cardiopulmonary bypass can result in significant reductions in levels. – Drugs that decrease blood levels: Phenobarbital, phenytoin, carbamazepine, and ticlopidine – Drugs that increase blood levels: Many antibiotics, antifungal agents, metoclopramide, verapamil, and diltiazem – Propofol does not appear to affect cyclosporine blood levels – Data on the effects of general anesthesia and cyclosporine pharmacokinetics are limited. • Allograft coronary artery disease (CAD): Present in ∼21% of patients 5 years posttransplant; it is the leading cause of death 3–5 years post-transplant. The coronary arteries undergo an accelerated process of coronary atherosclerosis (CAV). The etiology appears to be multifactorial; risk factors include pre-existing CAD, female donors, female recipients, and congenital cardiac disease. • Post-transplant hypertension: Present in ∼67% of patients at 5 years post-transplant. Cyclosporine therapy appears to be an important etiologic factor. Treatment with nifedipine is poorly tolerated because of vasodilation, and beta-blockers are best avoided. Diltiazem and ACE inhibitors are the drugs of choice (note that diltiazem can increase cyclosporine levels and dose needs to be adjusted accordingly). • Renal dysfunction: Present in ∼13% of patients at 5 years post-transplant. Cyclosporine therapy appears to be an important etiologic factor. In addition, it may be worsened by the simultaneous administration of NSAIDs or trimethoprim/sulfamethoxazole. Erythromycin and diltiazem elevate cyclosporine blood concentrations and can further deteriorate renal function.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The physiology of the denervated heart needs to be understood and appropriate medications should be chosen to treat bradycardia and hypotension. • Heart transplant patients may be undergoing rejection and manifesting myocardial dysfunction; additionally, they have increased CAV and cardiac dysrhythmias. A thorough evaluation of the cardiovascular system is mandated. • Strict aseptic precautions need to be followed and maintained; all intravascular and airway equipment should be handled with sterile gloves.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Angina, dyspnea, orthopnea, paroxysmal nocturnal dyspnea, limited functional capacity, syncope. • Fever, cough, or any other symptoms of systemic infection

History

• Medication compliance • Episodes of rejection • Exercise tolerance

Signs/Physical Exam

• Evaluate for infection • Jugular venous distention, pitting edema • Check for hypertension, arrhythmias. • Airway examination: Potential difficult airway because of lymphoproliferative disease and soft tissue hyperplasia because of corticosteroids.

TREATMENT HISTORY

About 5–10% of transplanted patients require a permanent pacemaker because of persistent dysrhythmias. MEDICATIONS

• Immunosuppressive agents: Cyclosporine, tacrolimus • Steroids • Anti-hypertensive: Diltiazem and ACE inhibitors

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Serum creatinine, liver function tests: Organ dysfunction secondary to immunosuppressive therapy. • Anti-rejection drug levels • Chest radiography: To rule out congestive heart failure and pneumonia. • EKG: Often two “p” waves are seen; first degree AV block is common. Incomplete and complete heart blocks are seen in 5–10% of patients. Dysrhythmias are common. • Echocardiogram: To evaluate LV function and myocardial ischemia. • Results of the annual follow-up and angiography should be followed • External pacemaker and defibrillator should be properly evaluated, if present.

CONCOMITANT ORGAN DYSFUNCTION

• Cardiac: Accelerated CAD, arrhythmias, hypertension • Renal dysfunction • Hepatobiliary disease: Neoplasm • Pancreatic disease: Relatively common in a transplanted patient.

CIRCUMSTANCES TO DELAY/CONDITIONS

Acute rejection, congestive heart failure, and persistent untreated arrhythmias may warrant delaying elective surgery in post-cardiac transplant patients.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Continue preoperative anti-rejection medications and steroids • Appropriate antibiotic prophylaxis should be administered (and repeated appropriately in the perioperative period) • Intravascular volume status should be addressed and optimized; consider fluid bolusing prior to induction (cardiac output is preload dependent). Special Concerns for Informed Consent

The need for invasive monitoring, telemetry, or ICU care INTRAOPERATIVE CARE Choice of Anesthesia

• Dependent upon the procedure; deep sedation, general, and regional anesthesia have all been performed safely. • Neuraxial anesthesia may be poorly tolerated because of the denervated heart. To minimize hypotension, slow, titrated dosing with local anesthetics should be administered, while maintaining the preload with IV fluids and pressors such as epinephrine or ephedrine. Monitors

• Standard ASA monitors • EKG will have two P waves, one from the native SA node and another from the donor SA node • Invasive monitoring depends upon the preoperative cardiac functional status and invasiveness of the surgery • Transesophageal echocardiogram may be an alternative to invasive hemodynamic monitoring • Large bore IV access should be secured to assure the ability to administer volume

Induction/Airway Management

• Orotracheal intubation is preferred to nasotracheal intubation because of the risk of infection. • Sympathetic response to direct laryngoscopy and intubation are typically absent. The posttransplant heart is denervated and associated with a loss of sympathetic and parasympathetic innervation. Sympathetic responses are delayed, blunted, and occur in response to circulating catecholamines. Maintenance

• Effects of volatile inhalational agents are well tolerated because most of the transplanted hearts have near-normal contractility. • Nitrous oxide may be used, as needed. • Depth of anesthesia: Tachyardia is an unreliable indicator. • Ventilator settings: Hyperventilation should be avoided because cyclosporine and tacrolimus can lower the seizure threshold. • Hemodynamics – Bradycardia: Positive chronotropic drugs such as isoproterenol may be needed. Vagolytic drugs such as atropine and glycopyrrolate are ineffective because of parasympathetic denervation. – Hypotension: Epinephrine and indirect acting vasopressors like ephedrine need to be used to restore BP. Glucagon is also useful as a positive inotropic and chronotropic agent. – Cardiac output is augmented by increasing the stroke volume; thus fluid boluses to increase preload are administered to restore the BP • In patients with renal dysfunction, choose drugs that do not rely heavily upon renal clearance and avoid nephrotoxic drugs. When muscle relaxation is given, consider the use of cisatracurium. • Ventricular dysrhythmias: Lidocaine should be used cautiously as it may have negative inotropic effects.

Extubation/Emergence

• Reversal agents: Neostigmine will not have any effect on the heart rate, but will produce effects at other muscarinic receptors. Reversal agents should be used concomitantly with anticholinergics to counteract the peripheral muscarinic effects. • Re-innervation of the transplanted heart may occur and has a more effective response to sympathetic nervous system output. However, this is highly variable and of uncertain functional significance.

FOLLOW-UP BED ACUITY

Depends upon the procedure, preoperative status, and intraoperative events. MEDICATIONS/LAB STUDIES/CONSULTS

• Continue immunosuppressive drugs • Proper functioning of the pacemaker needs to be ascertained. • Appropriate hemodynamic monitoring, including invasive monitors, needs to be continued.

COMPLICATIONS

Infection, worsening renal function, arrhythmias, hypertension, drug interactions.

REFERENCES

1. Kostopanagiotou G, et al. Anaesthetic and perioperative management of adult transplant recipients in nontransplant surgery. Anesth Analg. 1999;89(3):613–622.

2. Cheng DCH, Ong DD. Anaesthesia for non-cardiac surgery in heart-transplanted patients. Can J Anaesth. 1993;40(10):981–986.

ADDITIONAL READING

• Bready L, Dillman D, Noorily SH. Decision Making in Anesthesiology: an algorithmic approach: Chapter 165 • Hensley F, Martin ME, Gravlee GP. A Practical Approach to Cardiac Anesthesia: Chapter 15.

See Also (Topic, Algorithm, Electronic Media Element) • Laparoscopy • Trauma • Pacemaker dependent

CODES ICD9 V42.1 Heart replaced by transplant ICD10 Z94.1 Heart transplant status

CLINICAL PEARLS

• Laparoscopic cases are being increasingly performed in these patients. There is a slightly higher rate of conversion to open procedures (27% in transplant recipients compared to 11% in general population). Advantages include a shorter hospital stay, maintenance of oral immunosuppression, low morbidity, and early return to preoperative routine. • Trauma: Patients may be more susceptible to soft tissue damage and poor bone healing due to immunosuppressive therapy. Graft dysfunction secondary to injury should be ruled out. Initial resuscitation is similar to any other trauma patient. Pregnancy Considerations

• Maternal effects during pregnancy: Little effect on allograft survival; may have a higher risk of preeclampsia, preterm labor, and acute rejection. Immunosuppressive drugs can cause hepatorenal toxicity. Fetal effects: Low birth weight; abnormal function of the pancreas, liver and lymphocytes; immunosuppressive drugs are able to cross the placenta. In the second and third trimesters, these drugs affect the fetus’ immune system; however, they do not appear to be strongly associated with congenital anomalies in the first trimester.

POST-TONSILLAR BLEED Ranu Jain, MD

BASICS DESCRIPTION General

• Adenoidectomy and tonsillectomy are the most common operations performed in pediatric patients. Post-tonsillar bleeding that requires return to the operating room poses several challenges to the anaesthetist (e.g., full stomach, difficulty securing the airway, dehydration). • Blood supply to the tonsils – Arterial blood supply to the tonsils is via the right and left external carotid arteries and their branches. The superior pole is supplied by bilateral lesser palatine arteries and the inferior pole is supplied by bilateral branches of the dorsal lingual arteries and the ascending palatine arteries. – Venous return is to the plexus around the tonsillar capsule, the pharyngeal plexus, and bilateral lingual veins. – Post-tonsillectomy bleeding is usually venous in origin. • Classifications – Primary bleeds occur within 24 hours of surgery. Approximately 75% of bleeds occur within 6 hours. – Secondary bleeds occur up to 28 days post-surgery and are associated with sloughing of the eschar (dead tissue) overlying the tonsillar bed, loosened vessel ties, or infection from underlying chronic tonsillitis. – Primary bleeding is more profuse and brisk than secondary. – 77% of the bleeding originates in the tonsillar fossa, 27% in the nasopharynx, and 7% in both. ETIOLOGY/RISK FACTORS

• Increasing age • Male gender • Increased surgical time • Bleeding disorders • Use of NSAIDs • Surgical technique (blunt and sharp dissection have a 2.15% incidence compared to electrocautery with 0.9%). Position

Supine, with a shoulder roll Incision

None

Approximate Time 30–40 minutes EBL Expected

Depends on the time taken to find and stop the bleeding. The amount can range from minimal to significant. Hospital Stay

Typically an overnight stay

Special Equipment for Surgery Mouth gag

EPIDEMIOLOGY Prevalence

• Post-tonsillar bleeding can occur in ∼9% of all tonsillectomies. • Increases significantly with age; in 30–34 year olds it occurs in ∼18–20% of patients

Morbidity

Serious hemorrhage (need for blood transfusion or return to the operating room) is ∼1.4% and appears to increase with age ANESTHETIC GOALS/GUIDING PRINCIPLES

• Consider full stomach precautions and the increased risk of pulmonary aspiration from swallowed blood • Be prepared for a potentially difficult intubation due to blood in the airway, or airway edema from a previous intubation. • The post-tonsillectomy patient can be hypovolemic from several factors including emesis, ongoing blood loss, potential decreased oral intake due to postoperative pain. Thus, although tonsillar bleeds are emergencies, the patient must be resuscitated before the induction of anesthesia to avoid cardiovascular collapse.

PREOPERATIVE ASSESSMENT SYMPTOMS

• May present with altered mental status if severely hypovolemic. • It is very difficult to estimate the blood loss since large amounts of blood may be swallowed.

History

• Time of the original surgery • Time since last ingestion of food • Examine the previous anesthesia record, if available, to identify endotracheal tube size, ease of intubation, and opioid dosages. Opioids administered during the original operation must

be taken into account if treating a primary bleed, particularly when redosing morphine.

Signs/Physical Exam

• Mental status: Irritability and lethargy are late signs of hypovolemia. • Heart rate: Increases are seen in response to catecholamine release in order to maintain cardiac output. Bradycardia may result from metabolic acidosis and hypoxia and is a preterminal sign • BP: Hypotension is a late sign of hypovolemic shock in children. An acute blood loss of 30% may occur before the changes of BP are seen. • Perfusion: Capillary refill >2 seconds, mottling, pallor, cyanosis, and cold clammy skin are due to peripheral vasoconstriction thus poor perfusion. • Tachypnea: Develops as a compensatory response to metabolic acidosis (from severe anemia and poor perfusion). • Urine output may be decreased

MEDICATIONS

• IV fluids • Blood transfusion

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hemoglobin/hematocrit • Coagulation studies (PT/PTT, INR) • Blood gas analysis may reveal metabolic acidosis secondary to poor tissue perfusion.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Volume resuscitation should be performed with isotonic crystalloid or with blood, as appropriate. IV boluses of fluid, 20 mL/kg, should be administered and repeated if necessary after reassessment of the cardiovascular system. Large volumes of crystalloids may be required (40–60 mL/kg) • The patient may be very apprehensive. If premedication is necessary, benzodiazepines may be considered in certain scenarios with very close monitoring

Special Concerns for Informed Consent • Possible need for blood transfusion • Possible postoperative intubation

Antibiotics/Common Organisms

Not typically indicated, but may be considered based on surgeon preference. INTRAOPERATIVE CARE

Choice of Anesthesia

General endotracheal anesthesia Monitors

• Standard ASA monitors • Intravenous access may be placed preoperatively to provide fluid resuscitation prior to induction as well as allow for a rapid sequence induction. In hemodynamically stable patients, it may be acceptable to insert after mask induction. • An arterial line may be needed for closer monitoring of the BP, depending on co-morbidities

Induction/Airway Management

• Patients are considered to have a full stomach from the swallowed blood and the following should be available before starting the case. – Two suction devices with wide bore tubing, turned on, and available for immediate use. – Laryngoscope with different blades – Endotracheal tube, with smaller diameter size available in case of laryngeal edema – Weight appropriate LMA (backup rescue device) – The surgeon should be scrubbed and ready to operate. • There is some debate about the safest technique of anesthesia for a bleeding tonsil. The two common choices are: – Modified rapid sequence induction with cricoid pressure (requires an IV). Adequate preoxygenation in an anxious, bleeding child may be difficult; thus, facemask ventilation will be required. The doses of the induction agents are reduced (e.g., propofol 1–2 mg/kg, ketamine 1–2 mg/kg, etomidate 0.2 mg/kg) followed by the administration of succinylcholine (1.2–2 mg/kg) or rocuronium (1–1.2 mg/kg). Care must be taken not to inflate the stomach during facemask ventilation, as this can result in regurgitation and aspiration. – Inhalational induction in the head down, lateral position may be performed if the child has no IV access (and is hemodynamically stable). This technique helps drain blood from the airway by means of gravity and clots can be gently suctioned from the airway once an adequate depth of anesthesia is achieved. Oxygenation is well maintained during spontaneous ventilation. An IV line should be started once the patient is deep enough; muscle relaxant can be administered followed by intubation.

Maintenance

• A balanced anesthetic technique is typically used, with inhalational agents and careful titration of IV opioids. • Additional paralytic is not usually needed. • During the operation, warm fluid and blood should be administered on the basis of clinical assessment. The hematocrit should be checked after rehydration to have a better estimate of the blood loss. • Prophylactic anti-emetics (ondansetron, dexamethasone) should be given.

Extubation/Emergence

• Prior to extubation, the stomach should be suctioned and decompressed with an orogastric

tube. The endotracheal tube should be suctioned to eliminate secretions. • If there is any doubt of aspiration, direct visualization of the airway is recommended with the bronchoscope. • Reversal should be administered if a non-depolarizing agent is used. • The patient should be extubated when fully awake and with a normal gag and cough reflex.

FOLLOW-UP BED ACUITY

• Observe closely in an intermediate monitoring or intensive care unit. • Check hematocrit levels every 6–8 hours, until stable. • The ability to tolerate oral intake is usually a criteria for discharge.

ANALGESIA

• NSAIDs are not given. • Pain can be initially controlled by IV narcotics (e.g., fentanyl, morphine). • When the patient is able to eat, transition the patient to PO medications

COMPLICATIONS

• Laryngospasm/bronchospasm • Aspiration • Nausea/vomiting secondary to blood in the stomach (functions as a cathartic) • Infection • Anemia • Delayed emergence due to hypothermia, anemia, or multiple anesthetics

REFERENCES

1. Alexander Hons RJ, Kukreja R, Ford GR. Secondary post-tonsillectomy haemorrhage and informed consent. J Laryngol Otol. 2004;118:937–940. 2. Ozkiris M. Comparison of three techniques in pediatric tonsillectomy. Eur Arch Otorhinolaryngol. 2011;269(5):1497–1501. 3. Kim YS, Hong SJ, Choi J, et al. Spontaneous tonsillar hemorrhage and post-tonsillectomy hemorrhage. Clin Exp Otorhinolaryngol. 2010;3(1):56–58.

ADDITIONAL READING

• Alatas N, San I, Cengiz M. A mean red blood cell volume in tonsillectomy, adenoidectomy and adenotonsillectomy. Int J Pediatr Otorhinolaryngol. 2006;70(5):835–841.

See Also (Topic, Algorithm, Electronic Media Element) • Tonsillectomy and adenoidectomy

CODES

ICD9

998.11 Hemorrhage complicating a procedure ICD10

J95.830 Postproc hemor/hemtom of a resp sys org fol a resp sys proc

CLINICAL PEARLS

• The patient may be hypotensive and anemic, and may require resuscitation with fluids and blood products prior to anesthesia induction and/or perioperatively. • Most anaesthetists feel more comfortable with the IV rapid sequence induction in the supine position with the application of cricoid pressure to reduce the risk of aspiration. The use of muscle relaxants helps produce ideal conditions for intubation. • Always use full stomach precautions. • Anticipate difficulty visualizing the airway if there is ongoing active bleeding. • A smaller endotracheal tube may be necessary.

POST-DURAL PUNCTURE HEADACHE Rajeshwary Swamidurai, MD

BASICS DESCRIPTION

• Post-dural puncture headache (PDPH) usually manifests as a severe, incapacitating frontal or occipital headache following the introduction of a spinal or epidural needle into the dura with subsequent loss of CSF through the puncture site • It can occur following a diagnostic lumbar puncture, spinal, combined spinal/epidural or epidural anesthesia procedure. EPIDEMIOLOGY Prevalence

• All epidural procedures: Ranges from 0.19–4.4% (1,2) • Inadvertent dural puncture following labor epidurals: Ranges from 0.04–6% (3,4,5) • Incidence of PDPH following accidental dural puncture with epidural placement: Ranges from 50–85% (1,6) • Following spinal anesthesia (1): 40% with a 20 GA, 25% with a 25 GA, 2–10% with a 26 GA, and <2% with a 29 GA needle. • Following lumbar puncture: Ranges from 12–38% (7)

Morbidity

• Usually a self-limiting condition, with most headaches resolving within a week with conservative management. However, it can vary in intensity from mild to severe, and may be associated with photophobia, nausea, vomiting, neck stiffness, tinnitus, diplopia, and dizziness (1,6). • Symptoms following labor epidural placement may be so severe as to interfere with the patient’s ability to care for herself or her newborn and to interact with other family members (2). • Severe symptoms may delay hospital discharge and result in increased cost (1). • In one study, 17.8% of patients who developed a PDPH still complained of a headache 2–7 years following the procedure. 46.7% of patients complained of backache 1 year later (8). • Cranial nerve palsies, unmasking of pre-existing cerebral pathology, seizures, persistent CSF epidural fistulas, cranial subdural hematomas, intracerebral bleeding, and aneurysm rupture have been reported following dural puncture (9,10,11).

Mortality

Uncommon: Rare cases of fatal subdural hematomas have been reported. ETIOLOGY/RISK FACTORS

• Female gender: Almost twice as likely compared to males

• Young age: Rare over the age of 60 years; most commonly seen in 20–30 year olds • Pregnancy • Lower BMI • Larger gauge needle • Cutting versus pencil point needle • Greater number of attempts • Repeated dural punctures (12) • Perpendicular as opposed to parallel direction of needle bevel with respect to dural fibers • Previous history of PDPH • Inexperienced operator • Sleep deprivation, operator fatigue and effect of night work in junior personnel • Loss of resistance to air

PHYSIOLOGY/PATHOPHYSIOLOGY

• Several mechanisms have been postulated. The most commonly accepted thought is that the loss of CSF from the intrathecal space leads to a decrease in CSF volume and pressure, which in turn causes painful traction on the meninges and intracranial pain sensitive structures. Compensatory cerebral venous dilation may also occur, further giving rise to PDPH symptoms. • The loss of CSF volume may also lead to activation of adenosine receptors resulting in venous and arterial vasodilation (1).

PREVENTATIVE MEASURES

• Smaller, non-cutting needles should be used whenever possible. • If inadvertent dural puncture occurs with an epidural needle, strategies include: – Threading a catheter into the intrathecal space and leaving it in place for at least 24 hours; this may cause immediate plugging of the dural hole and promotion of an inflammatory reaction that helps to seal the hole (9). – 5-step strategy (1,2): Injecting the CSF back into the intrathecal space; advancing a catheter into the intrathecal space; injecting 3–5 mL of preservative-free saline through the catheter; using the catheter for labor analgesia with a bolus, followed by an infusion; and leaving the catheter in place for 12–20 hours. – Prophylactic epidural blood patch (injecting 15–20 mL of sterile venous blood into the epidural space) may not reduce the incidence of development, but may shorten the length and severity of symptoms (8,13). – Epidural morphine: May decrease PDPH incidence, need for EBP, and onset to PDPH (4) • Cosyntropin: Synthetic ACTH analog; associated with a significant reduction in the incidence of PDPH and need for EBP, along with significant prolongation of the time from accidental dural puncture to occurrence of PDPH (3).

PREOPERATIVE ASSESSMENT • History of dural puncture • Clinical symptoms: Incapacitating, dull or throbbing, frontal headache with radiation to the occiput

• Positional component: There is an exacerbation of the headache and symptoms when upright (usually within 20 seconds) and amelioration of symptoms when supine (usually within 20 seconds) (14). • Onset and duration: Usually develops within 7 days (typically within 48 hours) and resolves within 14 days of the procedure (9).

DIFFERENTIAL DIAGNOSIS

• Migraine • Caffeine-withdrawal headache • Meningitis • Sinus headache • Preeclampsia • Drugs (amphetamine, cocaine) • Brain tumor • Cerebral vein thrombosis • Cervical facet syndrome • Pneumocephalus-related headache • Lactation headache • Posterior leukoencephalopathy • Stroke (ischemic and hemorrhagic) • Subarachnoid/subdural hematoma

TREATMENT • Conservative management. Shown to provide varying degrees of symptom relief, but none have been shown to cure PDPH – Supine position: Ameliorates symptoms but may not provide therapeutic benefit – Hydration: May help to offset the decrease in CSF pressure. There is no evidence for therapeutic effect (1) – Caffeine: Causes cerebral vasoconstriction and thus may ameliorate symptoms, but the effect may be transient. Caffeine is a CNS stimulant and rare side effects include dizziness, jitteriness, flushing, and palpitations. Insomnia occurs in one-third of the patients and caffeine may lower the seizure threshold, unmasking seizures (15). – Theophylline: Causes potent cerebral vasoconstriction and may be used as an alternative to caffeine (1). – Sumatriptan: Serotonin agonist that causes cerebral vasoconstriction. It is expensive and must be administered subcutaneously (1). – Cosyntropin: Multiple doses may be effective after spinal anesthesia. Symptomatic relief is associated with increased beta endorphin levels and increased intravascular volume (16). – Hydrocortisone: May decrease the intensity in women who develop PDPH following spinal anesthesia for C-section (16). – Gabapentin: May be effective for prophylaxis and treatment of PDPH (16) – Abdominal binder: May reduce symptoms due to increased CSF pressure caused by increased intra-abdominal pressure. It is rarely used due to patient discomfort (6).

– Epidural dextran: Although postulated to remain in the epidural space longer due to the high viscosity and MW of dextran, there is no clear evidence for this, or for accelerated dural healing via an inflammatory process (1,2). It may be associated with anaphylaxis (10). • Although the above conservative, expectant measures may be carried out supportively, aggressive management should be considered in symptomatic patients to decrease patient discomfort, costs of extended stay, and return ER visits (5,9). – EBP remains the gold standard for treating patients with symptomatic PDPH, despite conservative measures (1,2,17). Its immediate effect is likely due to compression of the dura caused by injection of blood into the epidural space, which leads to increased CSF pressure and reduced traction on the pain sensitive structures. Its delayed effect likely involves formation of a clot at the site of the dural tear. The injected blood forms a plug at the dural hole and reduces further leakage of CSF. In one study, relief of symptoms has been reported as high as 93% after one EBP and 97% after a second EBP (17). If the headache persists after a second attempt, imaging studies should be considered, as well as other etiologies for headache (16). Efficacy appears to be improved when EBP is performed later as opposed to earlier, unknown reason. Level. Should be performed at or below the level of the dural tear due to the preferential cephalad spread of blood (10). Volume. Most effective amount has not been determined; 15–20 cc of sterile blood is generally injected and discontinued if and when the patient complains of back pain (9). Contraindications include any potential contraindications for epidural cannulation such as cutaneous or systemic infections, coagulopathies, or patient refusal (6,10). Complications of EBP include backache, neck pain, leg pain, paresthesias, mild pyrexia, bradycardia, pneumocephalus, intrathecal injection of blood, meningitis, arachnoiditis, and the possibility that further epidural blockade quality may be affected (11).

FOLLOW-UP • Routine spinal anesthesia or inadvertent puncture of the dura with an epidural needle: Patients should be followed closely for potential PDPH development. Since the presentation may be delayed, patients should be followed up at routine intervals following hospital discharge and instructed to return to the ER if symptoms develop. • EBP placement: Patients should be followed up at regular intervals to ensure that symptoms have not returned and there have been no complications stemming from the EBP.

REFERENCES

1. Kuczkowski KM. The management of accidental dural puncture in pregnant women: What does an obstetrician need to know? Arch Gynecol Obstet. 2007;275:125–131. 2. Kuczkowski KM. Post-dural puncture headache in the obstetric patient: An old problem. New solutions. Minerva Anestesiol. 2004;70:823–830. 3. Hakim SM. Cosyntropin for prophylaxis against postdural puncture headache after accidental dural puncture. Anesthesiology. 2010;113:413–420.

4. Al-metwalli RR. Epidural morphine injections for prevention of post dural puncture headache. Anaesthesia. 2008;63:847–850.

5. Angle P, Tang SLT, Thompson D, et al. Obstetric and pediatric anesthesia expectant management of postdural puncture headache increases hospital length of stay and emergency room visits. Can J Anaesth. 2005;52:397–402. 6. Kuntz KM, Kokmen E, Stevens JC, et al. Post-lumbar puncture headaches: Experience in 501 consecutive procedures. Neurology. 1992;42:1884–1887. 7. Jeskins GD, Moore PAS, Cooper GM, et al. Long term morbidity following dural puncture in an obstetric population. Int J Obstet Anesth. 2001;10:17–24. 8. Gaiser R. Postdural puncture headache. Curr Opin Anesthesiol. 2006;19:249–253. 9. Harrington BE. Postdural headache and the development of the epidural blood patch. Reg Anesth Pain Med. 2004;29:136–163.

10. Williams EJ, Beaulieu P, Fawcett WJ, et al. Efficacy of epidural blood patch in the obstetric population. Int J Obstet Anesth. 1999;8:105–109. 11. Scavone BM, Wong CA, Sullivan JT, et al. Efficacy of a prophylactic epidural blood patch in preventing post dural puncture headache in parturients after inadvertent dural puncture. Anesthesiology. 2004;101:1422–1427. 12. Paech M. Unexpected postpartum seizures associated with post-dural puncture headache treated with caffeine. Int J Obstet Anesth. 1996;5:43–46. 13. Thaw M, Paech MJ. Management of postdural puncture headache in the obstetric patient. Curr Opin Anesthesiol. 2008;21:288–292. 14. Safa-Tisseront V, Thormann F, Malassine P. Effectiveness of epidural blood patch in the management of post-dural puncture headache. Anesthesiology. 2001;95:334–339. 15. Bezov D, Lipton R, Ashina S. Post–dural puncture headache: Part I diagnosis, epidemiology, etiology, and pathophysiology. Headache. 2010;50:1144–1152. 16. ezov D, Ashina S, Lipton R. Post–dural puncture headache: Part II–Prevention, management, and Prognosis. Headache. 2010;50:1482–1498. 17. eeberger MD, Kaufmann M, Staender S, et al. Repeated dural punctures increase the incidence of postdural puncture headache. Anesth Analg. 1996;82:302–305. See Also (Topic, Algorithm, Electronic Media Element)

• Vaginal delivery • Epidural • Caudal epidural • Epidural steroid injections

CODES ICD9 349.0 Reaction to spinal or lumbar puncture

ICD10

G97.1 Other reaction to spinal and lumbar puncture

CLINICAL PEARLS

• Use smaller-sized and non-cutting needles for spinal and epidural procedures, when possible. • Following inadvertent dural puncture with an epidural needle, consider maneuvers listed above to help prevent PDPH development. • After development of a PDPH, consider performing a therapeutic epidural blood patch if symptoms are severe or persist, despite conservative therapeutic measures.

POSTOPERATIVE CHEST PAIN Philip Levin, MD

BASICS DESCRIPTION

• Postoperative chest pain can be caused/related to any part of the thorax, including the heart, lungs, esophagus, muscle, bone, and skin. Despite the possibility for innocuous causes (reflux), life-threatening causes (myocardial infarction [MI]) must be ruled out and, if identified, treated quickly. • It is a rare event that a patient complains of de novo anginal-type chest pain. Therefore, it is important to review the patient’s history and assess risks to help distinguish and discern chest pain due to cardiac origin. EPIDEMIOLOGY Prevalence

• Postoperative MI: 0–4%, depending on coronary artery disease (CAD) risk stratification. • Those at-risk for, or have CAD: 3.9% (1) for a major perioperative cardiac event

Mortality

Patients that have an MI after noncardiac surgery have an in-hospital mortality rate of 10– 15%. They also have an increased risk that persists for at least a year compared to those who did not have an MI. ETIOLOGY/RISK FACTORS

• Acute MI, angina: CAD, anemia secondary to surgery, hypertension (HTN), preoperative use of cocaine or other similar stimulants, recently placed coronary stents, high-risk surgery, cerebrovascular disease, use of insulin therapy for diabetes, signs of heart failure on preoperative examination, a preoperative serum creatinine >2 mg/dL, new long-standing ST-T wave changes noted intraoperatively. • Aortic dissection: s/p cardiac catheterization, aortic surgery. • Pulmonary embolism (PE): Obesity, prolonged immobility, femur fracture, pregnancy, cancer, history of prior PEs, family history of blood clots, arrhythmias, recently discontinued anticoagulation or antiplatelet medications. • Pneumothorax: Surgical injury to the chest or diaphragm, central line placement, brachial plexus block, ventilator complication. • Aspiration pneumonia: Poor motor control, extremes of age, emergency status, recent meal, morbid obesity, events during intubation or extubation, delayed gastric emptying, decreased gastric emptying, decreased lower esophageal sphincter tone. • Gastroesophageal reflux disease (GERD): History of GERD, decreased lower esophageal sphincter tone (e.g., pregnancy), certain medications (e.g., anticholinergics). • Perforated viscus: Complicated abdominal or thoracic surgery.

• Costochondritis: Thoracic surgery, lateral position during surgery, repetitive minor trauma to the chest wall during surgery.

PHYSIOLOGY/PATHOPHYSIOLOGY

• MI: Surgery with its associated trauma, pain, hypothermia, and anemia can induce an inflammatory, hypercoagulable state that can lead to coronary plaque rupture and arterial thrombosis. ST-segment elevated MI is associated with complete thrombotic occlusion of an epicardial coronary artery. Severe imbalances in myocardial oxygen supply and demand can also result in infarction. • Angina: Chest pain results from an imbalance between myocardial oxygen supply and demand that can result from increased levels of catecholamines and cortisol. It differs from an MI in that the arteries are not completely blocked and there is little or no permanent damage to the heart; however, it could be an indicator of impending MI. • Aortic dissection: A tear in the intimal layer is followed by formation and spread of a subintimal hematoma. This produces a false lumen, which can reduce blood flow to the major arteries arising from the aorta. If the dissection involves the pericardial space, cardiac tamponade may result. • PE: Occurs when a clot breaks loose and embolizes to block pulmonary blood vessels. Deep vein thrombosis (DVTs) in the lower extremities are triggered by venostasis, hypercoagulability, and vessel wall inflammation (increased in the perioperative period). Patients who have undergone gynecologic surgery, or major trauma may have deep vein thrombosis (DVTs) that move proximally to the popliteal vessels and from there embolize to the lungs. • Pneumothorax: Occurs with the entrance of air into the pleural cavity. A tension pneumothorax (air enters, but cannot exit as a result of a “ball-valve" mechanism) results in lung collapse, respiratory compromise, and mediastinal shifting. • Perforated viscus: A hole or a tear in the wall of the gastrointestinal tract allows air to enter the abdominal cavity, which irritates the diaphragm and can cause chest pain. • Aspiration pneumonia: Occurs when material (food, foreign body) or fluid (gastric contents, blood, or saliva) enters the lungs from the pharynx into the trachea. The consequences depend on the type, amount, and pH of material aspirated. Acidic gastric contents cause alveolar–capillary breakdown, resulting in interstitial edema, intraalveolar hemorrhage, atelectasis, increased airway resistance, and commonly hypoxia. • GERD: Occurs when gastric content refluxes into the esophagus, causing symptoms with or without associated esophageal mucosal injury (i.e., esophagitis). Usually the result of lower esophageal sphincter dysfunction. • Esophageal spasm: Remains unknown; however, it is believed to relate to a loss of inhibitory innervations in the body of the esophagus (2). • Costochondritis: An inflammatory process of the costochondral or costosternal joints that causes localized pain and tenderness.

PREVENTATIVE MEASURES

• Cardiac events: Patients on beta-blockers or statins prior to surgery should receive their dose in the perioperative period. Patients with recently placed bare metal stents should wait at least 6 weeks and those with drug-eluting stents should wait at least 1 year before

discontinuing dual platelet therapy to decrease the risk of acute stent thrombosis. Treat postoperative anemia, hypothermia, hypotension or HTN, and pain aggressively to decrease myocardial oxygen demand/supply mismatch. • PE: Early ambulation, mechanical and/or pharmacologic thromboprophylaxis have been demonstrated to be effective. • GERD: Administer acid reflux medication in the perioperative period.

PREOPERATIVE ASSESSMENT • MI or angina: Variable and can include tachycardia or bradycardia, hypotension or HTN, tachypnea, diaphoresis, and a fourth heart sound. Sign of CHF include S3 heart sound (gallop), pulmonary rales, lower extremity edema, and elevated jugular venous pressure. EKG changes: ST-segment elevation (≥2 mm in leads V1, V2 or V3 and ≥1 mm in the other leads) or depression (≥1 mm) in at least 2 contiguous leads, or symmetric inversion of T waves (≥1 mm) in at least 2 contiguous leads (3). New Q waves in two neighboring leads may be seen. • Aortic dissection: Hypertension (secondary to release of catecholamines), hypotension (excessive vagal tone), cardiac tamponade, hypovolemia, syncope, altered mental status. Dyspnea may be caused by CHF or tracheal/bronchial compression. Dysphagia form esophageal compression. A new diastolic murmur and a decrease in oxygen saturation may occur. A CT scan of the aortic vessels should be considered. • PE: Unilateral leg swelling from DVT, hypoxemia (<95%), and pulse >94 bpm. Massive PE causes hypotension due to acute cor pulmonale. Wheezing may be present. EKG changes: Prominent S wave in lead I; Q wave and inverted T wave in lead III pattern due to right ventricular strain. May also see peaked P waves in lead II, new right bundle branch block, right axis deviation, or new onset atrial fibrillation. Decreased oxygen saturation. D-dimer is a unique degradation product produced by plasmin-mediated proteolysis of cross-linked fibrin; levels are increased in PEs (nonspecific). A high resolution CT angiograph is a sensitive diagnostic tool; if it is not available, then a V/Q scan should be performed (less sensitive and specific). A duplex ultrasound of a DVT can also aid with diagnosis. • Pneumothorax: Decreased or absent breath sounds on the affected side with dyspnea, decreased pulse oximetry. When large, hypotension can result. • Aspiration pneumonia: Tachypnea, tachycardia; decreased breath sounds, rales, dullness to percussion over the area of consolidation; and hypoxemia. Chest radiograph is usually normal initially; a CT scan of the chest may yield results more quickly. • Perforated viscus: Rebound abdominal tenderness and fever. Hypotension secondary to significant blood loss or septic shock. An abdominal radiograph would show free air. • Costochondritis: Pain on palpation of the affected costochondral joints. • ECGs: Can be uninterpretable if the patient has known bundle branch block, chronic STsegment changes, or is pacer dependant. • Blood troponin level: To identify infarction; a typical rise and gradual fall is a sign of cardiac ischemia or PE. • Transthoracic or esophageal echocardiogram (TTE or TEE): New wall motion abnormalities on echocardiography are likely due to MI. New right ventricular dysfunction may also

suggest PE. • Radionuclide scan: New fixed cardiac defects on radionuclide scan is likely due to myocardial infarct. • Chest x-ray: Can rule out pneumothorax, check for enlarged mediastinum (aortic dissection), or infiltrate formation (aspiration pneumonia). For PE, the film may initially be normal; occasionally there may be dilation of the pulmonary vessels proximal to an embolism along with collapse of distal vessels. After 24–72 hours, the loss of pulmonary surfactant can cause atelectasis and pulmonary infiltrates which may appear like pneumonia. Aspiration pneumonia typically has a delayed presentation on radiography. • Arterial blood gas: Hypoxia and possible respiratory acidosis in pneumonia, pneumothorax, and PE. • White blood cell count (WBC): Increased with bacterial infections associated with aspiration pneumonia, as well as PE, and perforated viscus (if associated with sepsis). However, it can also be elevated after trauma and major operations. • Barium swallow: If a trial of proton pump inhibitors does not work and chest pain of an esophageal origin is still suspected, then a barium swallow can be done to rule out diffuse esophageal spasm or to detect hiatal hernias (associated with GERD). • Esophagogastroduodenoscopy (EGD): Can be done to rule out esophagitis and peptic ulcer disease. Esophageal manometry can be used to further detect diffuse esophageal spasm, and monitor the lower esophageal sphincter (which can help detect GERD).

DIFFERENTIAL DIAGNOSIS

• Cardiac: Acute MI, angina, aortic dissection • Pulmonary: Embolism, pneumothorax, aspiration pneumonia • Gastrointestinal: Acid reflux, esophagitis, esophageal spasm, perforated viscus • Musculocutaneous: Costochondritis

TREATMENT • MI and hemodynamically stable: Consult a cardiologist and possibly an intensivist. Medical management includes supplemental oxygen, morphine to adequately treat the patient’s pain (decreases sympathetic stimulation and has preload-reducing properties), nitroglycerin (decreases cardiac preload and causes coronary vasodilation), IV beta-blockers (decreases myocardial O2 consumption; may not be appropriate in patients with decompensated CHF,

severe COPD, severe hypotension from shock), and aspirin 325 mg (decreases platelet aggregation). IV unfractionated heparin may be given (to decrease thrombin formation) if suspicion of plaque rupture is high and the bleeding risks are acceptable. The cardiologist may also recommend starting an ACE inhibitor and a statin. • MI and hemodynamically unstable: Consult a cardiologist; cardiac catheterization with percutaneous coronary intervention may be necessary. Patients that have recently discontinued antithrombotic medications for cardiac stent placement should be catheterized immediately to rule out acute stent thrombosis. • Aortic dissection: Consult a thoracic surgeon, keep the heart rate between 60 and 80 bpm (beta-blockers), and systolic BP between 100 and 120. Treat pain adequately to maintain

pulse and BP within a target range. Urgent surgical intervention may be necessary depending on the location and type of dissection. • PE: Supplemental oxygen promotes pulmonary vascular dilation; vasoconstrictive agents and IV fluids should be given to treat hypotension. Anticoagulation with heparin, either unfractionated or low molecular weight, may be given to prevent clot progression; thrombolytic therapy may be considered. Consultation with the surgeon and an intensivist should be done prior to heparin and thrombolytic therapy since there is a great risk of major bleeding in postoperative patients. • Small pneumothorax: Typically resolves on its own without intervention. If large, a chest tube should be placed to decompress the air around the lung and allow for re-expansion. • Perforated viscus: Requires surgical intervention. • Aspiration pneumonia: Suction upper airway for any gastric content, provide supplemental oxygen, and consider intubation if signs of respiratory failure or poor oxygenation are present. Consider a pulmonary/critical care consult on the basis of severity. • GERD or esophagitis: Antacids, H2 blockers, or proton pump inhibitors. • Costochondritis: Patient reassurance and adequate pain control.

REFERENCES

1. Devereaux PJ, Goldman DJ, et al. Perioperative cardiac events in patients undergoing noncardiac surgery: A review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk. CMAJ. 2005;173(6):627–634. 2. Krieger-Grubel C, Hiscock R, Nandurkar S, et al. Physiology of diffuse esophageal spasm (DES)-when normal swallows are not normal. Neurogastroenterol Motil. 2010;22:1056– e279. 3. Devereaux PJ, Goldman L, Yusuf S, et al. Surveillance and prevention of major perioperative ischemic cardiac events in patients undergoing noncardiac surgery: A review. CMAJ. 2005;173(7):779–788. 4. Priebe HJ. Myocardial infarction-aetiology and prevention. Br J Anaesth. 2005;95(1):3–19.

ADDITIONAL READING

• Adesanya AO, de Lemos JA, Grilich NB. Management of perioperative myocardial infarction in noncardiac surgical patients. Chest. 2006;130:584–596.

See Also (Topic, Algorithm, Electronic Media Element) • Myocardial infarction • Pneumothorax • Aortic dissection • Aspiration pneumonia • Gastroesophageal reflux disease • Anemia

CODES

ICD9

• 338.18 Other acute postoperative pain • 786.50 Chest pain, unspecified ICD10

• G89.18 Other acute postprocedural pain • R07.9 Chest pain, unspecified

CLINICAL PEARLS

• Postoperative chest pain can be caused by many different etiologies. It is critical to immediately rule out and treat the life-threatening causes. • Review the patient’s medical history and intraoperative record for clues on the cause of postoperative chest pain. For example, does the patient have known CAD or GERD? • Perform a physical examination and order diagnostic testing as indicated • Implement treatment quickly and consult specialists as appropriate.

POSTOPERATIVE COGNITIVE DYSFUNCTION (POCD) Richard M. Rivera, MD

BASICS DESCRIPTION

• Postoperative cognitive dysfunction (POCD) describes a deterioration in cognition that can be seen following surgery. It manifests as acute or persistent disturbances in the information processing of the brain including: – Executive function – Language – Attention – Perception – Verbal abilities – Learning – Memory – Abstract thinking – However, patients typically remain oriented • The onset may begin within days of surgery and may last >1 year in 1% of elderly patients; it is considered a reversible condition in the majority of elderly patients. In addition, POCD differs from delirium, postoperative delirium (POD), and dementia. – Delirium (DSMIV) is defined as a change in mental status characterized by a reduced awareness of the environment and disturbance in attention; it may be accompanied by hallucinations, disorientation, or temporary memory dysfunction. In addition, the patient may express hypoactive, hyperactive, or mixed psychoactive behavior. – POD describes delirium in the postoperative surgical patient. Patients are often lucid in the recovery room, with onset developing between postoperative days 1–3. – Dementia (DSMIV) is a progressive decline in cognition or behavior from a prior level of functioning in one or more of the following: Memory, reasoning, language, visual processes, executive functions, social-interpersonal behaviors, and personality. It is caused by brain disease. • At this time, POCD lacks a consensus definition and studies face several methodologic limitations, despite the growing awareness within the field of anesthesiology and amongst the public. EPIDEMIOLOGY Prevalence

• At 1 week postoperatively, POCD following: – Cardiac surgery: 30–80% – Major noncardiac surgery: 19–26% – Minor surgery: 7% • No difference seen with general versus regional anesthesia

Prevalence

Geriatric patients are more likely to have POCD at 1 week and 3 months postoperatively compared to their younger cohorts Morbidity

• Results in patients requiring longer hospital stays and greater assistance at home • Increased likelihood of dropping out of the labor market.

Mortality

If present at the time of hospital discharge and persists at 3 months, there is an increased mortality within 1 year after surgery. ETIOLOGY/RISK FACTORS • Increasing age • Major surgery • Stress response • Hypotension • Cerebral hypoxia • Microemboli • Cardiac surgery • Anesthesia • Genetics

PHYSIOLOGY/PATHOPHYSIOLOGY

• The definitive cause of POCD remains unknown. – Age: Changes in the white and gray matter may decrease the “cognitive reserve.” This may be somewhat offset by higher levels of education and physical activity. – Stress response: Surgery results in the release of neuroendocrine hormones, cytokines, and alterations in cortisol. Major procedures may have an increased stress response. – Hypotension: Studies have shown that elderly, hypertensive patients with low intraoperative mean arterial pressures have increased cognitive impairment at 1 day and 1 week postoperatively. – Cerebral hypoxia: In cardiac surgery, a decrease in cerebral oxygen saturation has been associated with an increased risk of POCD – Microemboli, as measured by Doppler in orthopedic cases, may be a factor in the development of POCD. – Regional anesthesia does not reduce the risk of POCD as compared to general anesthesia. However, a greater depth of anesthesia has been associated with a >1 year mortality in elderly patients – Genetically, the APO-E 4 allele is associated with Alzheimer’s disease and is present in a subgroup of POCD patients • Future research appears to be focused on: – The mechanism by which age may play a role – The effects of genetics on predisposition – The relationship between POD and POCD

– Preoperative “mental exercise training” as well as postoperative interventions to decrease the incidence and/or duration of POCD

PREVENTATIVE MEASURES

• There are no specific, proven methods for prevention. • Preoperative testing may be considered in patients at risk for POCD. • Maintenance of systolic BP at >90 mm Hg, especially in hypertensive patients • Maintain an adequate cerebral perfusion pressure, particularly in the beach-chair position or cardiac surgical procedures • Consider monitoring the depth of anesthesia with a BIS monitor to avoid excessive levels • Reduce perioperative stress by placing continuous infusion neuraxial or regional blocks preoperatively and maintaining them in the intraoperative and postoperative period. • Anesthetic choice, regional versus general, does not appear to influence the incidence of POCD

PREOPERATIVE ASSESSMENT • At this time, there is no standard, consensus testing for POCD. Diagnosis is on the basis of establishing a decrease between preoperative and postoperative cognitive functions. • There are several tests available to aid in evaluating memory, sensorimotor speed, cognitive flexibility, and aspects of motor performance: – Mini mental status examination (MMSE): Frequently utilized and takes approximately 5– 10 minutes to administer – Clock drawing test – List learning test – Paragraph or story learning test

DIFFERENTIAL DIAGNOSIS

• POD • Dementia • Acute alcohol withdrawal • Residual anesthesia/analgesics

TREATMENT There is no specific treatment of POCD at this time.

FOLLOW-UP • If a patient is suspected of, or diagnosed with POCD, a discussion should be made with the patient, family, and surgeon. • Patients may require greater assistance after discharge and follow-up with a geriatrician or neurologist should be considered and arranged, if appropriate.

REFERENCES

1. Silverstein H, et al. Central nervous system dysfunction after noncardiac surgery and anesthesia in the elderly. Anesth. 2007;106(3):622–628. 2. Ramaiah R. Postoperative cognitive dysfunction in the elderly. Anesth Clin. 2009;27:485– 496.

3. Monk T, et al. Predictors of cognitive dysfunction after major noncardiac surgery. Anesth. 2008;108(1):18–30. 4. Monk TG, Price CC. Postoperative cognitive disorders. Curr Opin Crit Care. 2011;17(4):376–381.

5. Price CC, Garvan CW, Monk TG. Type and severity of cognitive decline in older adults after noncardiac surgery. Anesthesiology. 2008;108(1):8–17.

6. ekker A, Lee C, de Santi S, et al. Does mild cognitive impairment increase the risk of developing postoperative cognitive dysfunction? Am J Surg. 2010;199(6):782–788. 7. sai TL, Sands LP, Leung JM. An update on postoperative cognitive dysfunction. Adv Anesth. 2010;28(1):269–284.

ADDITIONAL READING

• Silbert B, Evered L, Scott DA. Cognitive dysfunction in the elderly: Is anesthesia implicated? Best Pract Res Clin Anaesthesiol. 2011;25(3):379–393. 8. Bilotta F, Doronzio A, Stazi E, et al. Early postoperative cognitive dysfunction and postoperative delirium after anaesthesia with various hypnotics: Study protocol for a randomized controlled trial–the PINOCCHIO trial. Trials. 2011;6(12):170. See Also (Topic, Algorithm, Electronic Media Element) • Perioperative hypertension • Geriatric physiology

CODES ICD9 293.9 Unspecified transient mental disorder in conditions classified elsewhere ICD10 G97.82 Oth postproc complications and disorders of nervous sys

CLINICAL PEARLS

• When in the beach-chair position for neurosurgical procedures, the arterial line should be placed and zeroed at the level of the auditory meatus • Consider the use of preemptive analgesia with regional or neuraxial blocks to minimize the surgical stress response. • Consider BIS monitoring to titrate medication and volatile agent dosing.

POSTOPERATIVE DELIRIUM Carlee Clark, MD Horst Rieke, MD, PhD

BASICS DESCRIPTION

• The diagnostic and statistical manual (DSM) of Mental Disorders IV diagnosis of delirium is a: – Disturbance of consciousness with inattention accompanied by a change in cognition or perceptual disturbance that develops over a short period of time (hours to days) and fluctuates over time • It exists on a continuum: – Hyperactive: Abnormal psychomotor activity with picking or pulling at lines and monitors, combative with staff and family, visual hallucinations, or increased state of arousal and hypervigilance; more common during the night. – Hypoactive: Uncomplaining, lying listless, and may even follow commands; most common and most commonly undiagnosed. – Hypoalert: May seem sedated or somnolent. • Postoperative delirium has a temporal relationship with surgery and frequently occurs between postoperative days 2 and 7 (1). EPIDEMIOLOGY Prevalence

• Postoperative delirium – Hip fracture 4–53% (2) – Postcardiac surgery 32–38.5% (3) – Elderly patients 15–53% (4) – General surgery 5–15% (5) • Trauma and ICU patients 60–80% (6) • Medical and surgical inpatients 15–60% (7)

Prevalence

Ranges from 5–50% Morbidity

• Increased length of hospital and ICU stay • Increased hospital cost • Greater dependency of care on discharge • Higher nursing home disposition rates • Cognitive deterioration

Mortality

• Postoperative delirium patients have a 15–20% mortality rate (8) • Elderly patients and ICU patients with delirium have an increased 6-month mortality (9,10). • Patients with delirium have a 62% increase in 12-month mortality (11).

ETIOLOGY/RISK FACTORS

• Preoperative risk factors – Critical illness – Severity of illness – Prior history of delirium – History of alcohol abuse – History of tobacco use – Poor preoperative functional status – Preoperative use of narcotic analgesics – Preoperative depression and dementia – History of Parkinson’s disease • Intraoperative risk factors – Vascular surgery – Cardiac surgery – Hip fracture – Emergent surgery – Greater intraoperative blood loss • Postoperative risk factors – Postoperative transfusions – Postoperative hematocrit <30% – Severe postoperative pain – High doses of benzodiazepines – Postoperative polypharmacy – Electrolyte abnormalities

PHYSIOLOGY/PATHOPHYSIOLOGY

• The exact pathophysiology in the development and progression of delirium is unknown, but it is associated with many different etiologies. • Neurotransmitter imbalance: A relative deficiency of cholinergic transmission can result in decreased central cholinergic and increased dopaminergic, GABA, and serotonergic neurotransmission. The aging brain has a relative deficiency of acetylcholine, as do dementia patients, resulting in greater susceptibility. Perioperatively: – Medications: Steroids, anticholinergics, benzodiazepines, opioids, some anesthetics, anticonvulsants, bromides, and antibiotics – Metabolic and endocrine derangements: Electrolyte abnormalities, dehydration – Withdrawal syndromes: Alcohol, benzodiazepines, or opioids • Type of anesthesia: There is no difference in the incidence of delirium when comparing patients having undergone MAC, general anesthesia, or a regional anesthetic (12,13). • Systemic inflammation secondary to the surgical procedure: An inflammatory response to surgical tissue injury can result in cytokine, TNK, histamine, and cortisol release, as well as proliferation of macrophages. These inflammatory mediators may interfere with normal

metabolism and function, thereby, causing delirium (14–16). • Anatomic defects: Anatomic changes in the brain seen on CT, MRI, and PET scanning have implicated the prefrontal, non-dominant posterior parietal, basal ganglia, and temporal– occipital cortex (17).

PREVENTATIVE MEASURES

Identification of patients with preoperative risk factors and minimization of intraoperative and postoperative risk factors. “Prophylactic” measures mimic therapeutic measures. • Cardiac surgery delirium prediction score (18) • General elective surgery delirium prediction score (19) • Nonpharmacologic measures (see Treatment) • Haloperidol prior to, and following, the surgical procedure; little data to support this practice. • Atypical antipsychotics; prophylactic efficacy is not supported by data • Dexmedetomidine in ventilator-dependent patients may result in decreased delirium and resolution of symptoms quicker than those sedated with benzodiazepines (20). • Avoidance of benzodiazepines • Avoidance of new polypharmacy • Adequate pain control

PREOPERATIVE ASSESSMENT • Delirium is a diagnosis based on clinical signs and symptoms defined in the DSM IV – Rapid onset with a fluctuating course – Disorganized thinking – Alterations in level of consciousness with inattention • It is a diagnosis of exclusion and organic causes need to be excluded: – Thorough history and physical examination looking for risk factors or new pathology. – Basic metabolic panel, CBC, arterial blood gas – Pulse oximetry, temperature, telemetry, and BP monitoring • Patients frequently have sleep disturbances • Confusion assessment method for the ICU (CAM-ICU): Can be used in verbal and nonverbal patients.

DIFFERENTIAL DIAGNOSIS

• Hypoxemia • Hypercarbia • CNS or systemic infection • Cerebrovascular accident • Hypoglycemia/hyperglycemia • Electrolyte abnormalities • Urinary retention • Alcohol or medication withdrawal • Dementia • Medication administration

TREATMENT • Focus on improving patient cognition and decreasing adverse events such as aspiration, prolonged immobilization, impaired cognition, or death. • Non-pharmacologic interventions should be initiated first. – Reorientation to person, place, and time is important. It is helpful to encourage the family members to do the same. – Improve sleep quantity and quality; sleep aids if necessary. – Correct day/night cycle; lights on during the day and off at night. – Stimulating activities multiple times a day; visiting with family, watching television, puzzles – Early mobilization, range of motion activities and physical therapy – Replace glasses and hearing aids as soon as possible – Remove unnecessary lines, particularly Foley catheters and central lines – Avoid restraints if possible – Nutrition and hydration – Avoid urinary retention – Patients may require sitters to prevent harm to themselves. • Avoid medications that can worsen postoperative delirium such as benzodiazepines, anticholinergics, steroids, and opioids. • Optimize the postoperative pain regimen by using multimodal analgesia when possible to decrease the amount of opioids required. • Antipsychotics: IV haloperidol is the drug of choice for delirium treatment as recommended by The American Psychiatric Association and the Society of Critical Care. – Mechanism of action (MOA): Dopamine receptor antagonist resulting in decreased dopamine neurotransmission. – Dosing: Mild symptoms and for the elderly: 0.5–2 mg IV; moderate symptoms: 2.5–5 mg IV; severe symptoms: 5–10 mg IV. Administer every 30 minutes until agitation has resolved. – Maintenance: Dosing should be scheduled every 4–6 hours with PRN dosing for acute episodes. Maximum daily dosing is 20 mg. – Side effects: Sedation, prolongation of QT on EKG, it is not FDA approved for this purpose and carries a Black Box warning for arrhythmias (including Torsade de Pointes) extrapyramidal signs, minimal anticholinergic effects. – A baseline ECG should be available prior to initiation of therapy. • Atypical antipsychotics should be considered when patients have a contraindication to haloperidol. – Quetiapine MOA: Receptor antagonist at dopamine, serotonin, histamine and alpha 1 and 2 adrenergic receptors. Dosing: 25 mg–100 mg PO BID. Maximum daily dose is 200–400 mg. Not appropriate for acute agitation, as it is only available in oral form. Side effects: Prolongation of QT on ECG, extrapyramidal signs, anticholinergic effects, sedation

– Olanzapine MOA: Receptor antagonist at dopamine, serotonin, and histamine receptors. Dosing: 2.5–5 mg PO/IM/sublingual daily. Maximum daily dose is 20 mg. Can be given IM for acute agitation. Side effects: Prolongation of QT on ECG, extrapyramidal signs, anticholinergic effects, sedation – Dexmedetomidine MOA: Alpha 2 adrenergic receptor agonist Dosing: 0.2–1.0 mcg/kg/hr Side effects: Bradycardia, hypotension More data is needed before applying to nonventilated patients with delirium (20).

FOLLOW-UP • Patients with delirium need to be continuously reassessed for clinical improvement or deterioration. Transfer to an ICU is common. • Pharmacologic agents can be stopped a few days after the cessation of delirium.

REFERENCES

1. arcantonio ER, Goldman L, Mangione CM. A rule for prediction of delirium after noncardiac surgery. JAMA. 1994;27:134–139. 2. Bruce AJ, Ritchie CW, Blizard R, et al. The incidence of delirium associated with orthopedic surgery: A meta-analytic review. Int Psychogeriatr. 2007;19(2):197–214. 3. ockalingam S, Parekh N, Bogoch I, et al. Delirium in the postoperative cardiac patient: A review. J Cad Surg. 2005;20(6):560–567. 4. Demeure MJ, Fain MJ. The elderly surgical patient and postoperative delirium. J Am Coll Surg. 2006;203:752–757. 5. Bekker AY, Weeks EJ. Cognitive function after anaesthesia in the elderly. Best Pract Res Clin Anaesthesiol. 2003;17:259–272. 6. Ishaq L, McMillan M, Taylor S, et al. The impact of delirium on clinical outcomes in mechanically ventilated surgical and trauma patients. Crit Care Med. 2009;37(6):1898– 1905. 7. Ely EW, Siegel MD, Inouye SK. Delirium in the intensive care unit: An underrecognized syndrome of organ dysfunction. Semin Resp Crit Care Med. 2001;22:115–126. 8. Ansaloni L, Catena F, Chattat R, et al. Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery. Br J Surg. 2010;97(2):273–280. 9. Fann JR.The epidemiology of delirium: A review of studies and methodological issues. Semin Clin Neuropsychiatry. 2000;5:64–74. 10. Ely EW, Shintani A, Truman B, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291:1753–1762. 11. Leslie D, Zhang Y, Holford T, et al. Premature death associated with delirium at 1-year

follow-up. Arch Int Med. 2005;165:1657–1662. 12. Papaioannou A, Fraidakis O, Michaloudis D, et al. The impact of the type of anaesthesia on cognitive status and delirium during the first postoperative days in elderly patients. Eur.J.Anaesthesiol. 2005;22:492–499. 13. Williams-Russo P, Sharrock NE, Mattis S, et al. Cognitive effects after epidural vs general anesthesia in older adults: A randomized trial. JAMA. 1995;274:44–50. 14. Saper CB.Neurobiological basis of fever. Ann NY Acad Sci. 1998;856:90–94.

15. Bierhaus A, Humpert PM, Nawroth PP. NF-B as a molecular link betweenpsychosocial stress and organ dysfunction. Pediatri Nephrol. 2004;19:1189–1191. 16. ichers MC, Maes M. The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-α-induced depression. J Psychiatry Neurosci. 2004;29:11– 17. 17. Trzepacz P.Is there a final common neural pathway in delirium? Focus on acetylcholine and dopamine. Sem ClinNeuropsychiatry.2000;5:132–148. 18. Rudolph JL, Jones RN, Levkoff S. Derivation and validation of a preoperative prediction rule for delirium after cardiac surgery. Circulation. 2009;119:229–236. 19. arcantonio EJ, Goldman L, Mangione CM, et al. A clinical prediction rule for delirium after elective noncardiac surgery. JAMA. 1994;271:134–139. 20. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: A randomized trial. JAMA. 2009;301(5):489–499. 21. Jacobi J, et al.American Psychiatric Association and the Society of Critical Care practice guidelines for delirium. Crit Care Med. 2002;30:119–141. • www.ICUdelirium.org See Also (Topic, Algorithm, Electronic Media Element) • Postoperative cognitive dysfunction • Hypoxia, postoperatively • Postoperative stroke

CODES ICD9 293.9 Unspecified transient mental disorder in conditions classified elsewhere ICD10 G97.82 Oth postproc complications and disorders of nervous sys

CLINICAL PEARLS

• Postoperative delirium frequently occurs postoperative days 2–7 • Delirium has three subtypes: Hyperactive, hypoactive, and mixed. Hypoactive most commonly goes undiagnosed because the patient is not disruptive.

• Delirium screening can aid with identifying patients at risk and minimizing perioperative risk factors as well as implementing prophylactic measures. Nonpharmacologic therapy is first-line for prevention and treatment of delirium. • Haloperidol is the drug of choice for delirium treatment. The patient should have an ECG before initiating haloperidol therapy secondary to the potential for QT prolongation.

POSTOPERATIVE HYPOXIA Suzanne Strom, MD

BASICS DESCRIPTION

Postoperative hypoxia is defined as an arterial oxygen tension (PaO2) <60 mm Hg, which

correlates with SpO2 <90%. EPIDEMIOLOGY Prevalence

• Postoperative respiratory problems are the most frequently occurring complication during the recovery period. • Up to 30% of postoperative patients have oxygen saturations (SpO2) <90% while breathing room air.

ETIOLOGY/RISK FACTORS

• The major etiologies for postoperative hypoxia are airway obstruction and hypoventilation. • Airway obstruction. Causes include: – The tongue falling back against the posterior pharynx – Laryngospasm – Glottic edema – Secretions – Emesis or blood in the airway – Hematoma in the neck from surgery; external pressure on the trachea – Gauze packing left unintentionally in the mouth, airway, or esophagus. Can cause immediate or delayed complete airway obstruction. – Vocal cord paralysis • Hypoventilation: Defined as a PaCO2 >45 mm Hg and is common following general anesthesia. In most cases, the hypoventilation is mild and overlooked unless the PaCO2 is

>60 mm Hg or arterial blood pH is <7.25. Hypercarbia is a sympathetic stimulant that can manifest as tachycardia, hypertension, and cardiac irritability. Decreased respiratory drive can result from: – Residual anesthetic agents and postoperative analgesics (most common) – Residual neuromuscular blockade as a result of inadequate reversal, overdose, hypothermia, pharmacologic interactions with antibiotics (clindamycin), renal or hepatic dysfunction, or electrolyte disturbances. – CNS lesion or ischemia – Inadequate respirations can result from splinting with incisional pain, diaphragmatic dysfunction, abdominal distention, or firm dressings.

• Decreased functional residual capacity (FRC) causes increased right-to-left intrapulmonary shunting relative to closing capacity (common cause). Causes include: – Atelectasis – Parenchymal infiltrates (including those caused by aspiration) – Large pneumothorax – Pleural effusion – Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) – Absorption atelectasis – Bronchospasm • Other causes that need to be ruled out when the above-mentioned do not appear to explain hypoxia: – Low cardiac output caused by myocardial infarction, congestive heart failure, shock, arrhythmias, or cardiac tamponade. – Increased O2 consumption from shivering – Pulmonary embolism, especially if the patient complains of dyspnea • Risk factors: – Extremes of age – Pregnancy – Obesity – Smokers – Pre-existing cardiac or respiratory disease.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Hypoxia results in inadequate oxygen supply for normal cellular metabolism and oxidative phosphorylation. In low oxygen states, anaerobic metabolism proceeds to continue manufacturing ATP; however, it is inefficient and produces lactic acid. Progressive lactic acidosis impairs enzymatic function and concentration gradients. • In the face of decreased oxygen delivery and increased myocardial oxygen demand, ischemia and worsened acidosis can result. The final result of continued hypoxia is cell death. • Hypoxia is sensed in the carotid bodies (at the bifurcation of the common carotid arteries) and the aortic bodies (surrounding the aortic arch). These peripheral sensors interact with central respiratory centers via the glossopharyngeal nerves to produce reflexive increases in alveolar ventilation. However, hypoxia receptor activity does not appreciably increase until the PaO2 decreases <50 mm Hg, at which point the SpO2 is 80%.

• Signs: Hypoxia stimulates the sympathetic system and initially can cause tachycardia, hypertension, and increased cardiac output. Late signs of hypoxia include myocardial dysrhythmias, tachycardia, bradycardia, hypertension, hypotension, and cardiac arrest. • Concomitant hypercarbia should also be considered, which can cause a respiratory acidosis in addition to the metabolic (lactic) acidosis caused by hypoxia.

PREVENTATIVE MEASURES – Supplemental FiO2:

– Should be considered in all patients who have received deep sedation or general

anesthesia in the postoperative period; transient hypoxia can develop even in healthy patients. – Can be discontinued if room air SpO2 measurements are acceptable and the patient is

relatively alert and awake. An arterial blood gas can help guide decisions in challenging cases. – Longer periods of administration should be considered in patients at increased risk for hypoxia (impaired baseline status, abdominal or thoracic procedures). – When continued upon discharge from the recovery room, care should be taken in those with COPD and a history of CO2 retention that are being transferred to a unit which does

not have constant pulse oximetry measurement. • The head of the bed should be elevated at least 30° if the patient is responsive unless contraindicated by the surgical procedure (e.g., recent femoral sheath access). Similarly, coughing and deep breathing should be encouraged.

PREOPERATIVE ASSESSMENT • Verify low SpO2 measurement.

– Ensure that the SpO2 rate correlates with the EKG tracing

– Verify accurate waveform – Move pulse oximetry probe to different fingers, an earlobe, nostril or nasal ala – Measure arterial blood gas to confirm; also aids with differentiating between absolute shunt/large V/Q mismatching and low FiO2, hypoventilation, and smaller V/Q

mismatching. • Correlation between PaO2 and SpO2 may be affected by hypothermia, poor circulation,

electrocautery, motion, ambient lighting, and methylene blue administration. • Evaluate for – Respiratory rate (opioid-induced hypoventilation presents with low respiratory rate and large tidal volumes) – Flow of air – Respiratory pattern – Labored breathing (accessory muscles) – Chest wall movement – Excessive somnolence – Airway obstruction. In total obstruction, the chest wall descends as the abdomen rises during each respiration instead of the abdomen and chest rising together. With partial obstruction, usually presents as sonorous respirations. • In an awake patient, assessment of neuromuscular blockade can be done by having the patient sustain a head lift for 5 seconds or by a nerve stimulator in an unconscious patient. • Portable chest x-ray should be obtained to ascertain atelectasis, infiltrates, or pneumothorax.

DIFFERENTIAL DIAGNOSIS

Evaluating alveolar to arterial (A–a) gradient may help determine the cause. The alveolar oxygen equation is as follows:

• PAO2 = FiO2 (PB − PH2O) − (PaCO2/RQ)

– PAO2 = partial pressure of oxygen in the alveoli – FiO2 = fraction of inspired oxygen

– Pb = barometric pressure (sea level = 760 mm Hg)

– PH2O = partial pressure of water vapor in the airway (47 mm Hg)

– PaCO2 = partial pressure of carbon dioxide in the blood

TREATMENT • Increase the FiO2 while evaluating for reversible causes.

• Since airway obstruction is the most likely cause, start with arousal of the somnolent patient, followed by chin lift, jaw thrust, oro- and nasopharyngeal airway insertion. Elevation of the head of the bed can improve anatomic considerations. • If laryngospasm is suspected, continuous positive pressure may be implemented to “break” it. If unsuccessful, administer succinylcholine (20 mg/70 kg) with continuous positive pressure ventilation. • If respiratory depression is caused by opioids, consider reversal with naloxone titrated in 0.04 mg increments in adults. Watch for side effects such as pain, sympathetic stimulation, and pulmonary edema. • Treat residual neuromuscular paralysis with additional cholinesterase inhibitors if the maximum dose has not been achieved. In the event that it has been attained, supportive measures should be taken: – Bag mask ventilation – Invasive airway instrumentation (LMA or ETT) following induction • Laryngeal mask airway (LMA) insertion or endotracheal intubation may be necessary to reestablish ventilation if the patient is unconscious, hypercarbic, or acidotic. Repeated airway instrumentation and intraoperative fluid administration can worsen the glottic view from original laryngoscopy at the beginning of surgery; alternative techniques for securing the airway should be available such as a bougie, cricothyrotomy, indirect video laryngoscopy, or transtracheal jet ventilation. • Glottic edema leading to stridor should be treated with IV dexamethasone 0.5 mg/kg up to 10 mg (slow onset) or aerosolized racemic epinephrine 0.5 mL of a 2.25% solution with 3 mL of normal saline (faster onset). • If wound hematoma is suspected, immediately open the wound. • Maintain adequate cardiac output and hemoglobin levels.

REFERENCES

1. Noble DW. Hypoxia following surgery – an unnecessary cause of morbidity and mortality? Minerva Anestesiol. 2003;69(5):447–450. 2. Tyler IL, Tantisira B, Winter PM, et al. Continuous monitoring of arterial oxygen saturation with pulse oximetry during transfer to the recovery room. Anesth Analg. 1985;64:1108–

1112. 3. Pedersen T, Moller AM, Hoyannisyan K. Pulse Oximetry for Perioperative monitoring. Cochrane Database Syst Rev. 2009;(4):CD002013. See Also (Topic, Algorithm, Electronic Media Element) • Oxygen content • Hypoxia intraoperative • Difficult airway • Laryngospasm

CODES ICD9 • 799.02 Hypoxemia • 997.01 Central nervous system complication ICD10 • G97.82 Oth postproc complications and disorders of nervous sys • R09.02 Hypoxemia

CLINICAL PEARLS

• Always assume that a low SpO2 is accurate until proven otherwise.

• Hypoxia should always be at the top of a differential diagnosis for abnormal cardiovascular vital signs such as hypertension, tachycardia, and arrhythmia, as well as nausea and altered mental status in a postoperative patient.

POSTOPERATIVE JAUNDICE Catherine Dawson Tobin, MD William David Stoll, MD

BASICS DESCRIPTION

• Jaundice in the postoperative period may result from a combination of hypotension, hypoxemia, pigment overload, or sepsis, with the clinical picture resembling hepatitis. It is: – Usually evident within 2 weeks after surgery – Can occur in up to 47% of patients with cirrhosis – Unusual in patients without liver disease • Abnormal liver chemistry tests (LCTs), on the other hand, can range from 25–75% in patients without liver disease; mild elevations are thus considered typical. • Postoperative LCT abnormalities and jaundice are usually categorized and worked-up in one of the following 4 groups: – Increased bilirubin production (pre-hepatic) – Hepatocellular disease (intrahepatic) – Cholestatic disorders (posthepatic) – Pre-existing liver disease EPIDEMIOLOGY Prevalence

• Elective abdominal surgery: <1% (1)[A] • Cardiac surgery: 26.5% – Higher in mitral valve replacement (MVR) combined with coronary artery bypass graft (CABG) than CABG alone and aortic valve replacement (AVR) plus CABG (2)[B] – Heart transplantation: 57% (3)[B] • Postoperative acute acalculous cholecystitis is more common in men than women, represents 70% of all acute cholecystitis in children (1)[A]. Morbidity

A history of pre-operative cirrhosis is associated with a 30% complication rate with surgery, the most common being pneumonia (4)[B]. Cirrhosis is a common cause of jaundice

Mortality

• Postoperative jaundice is associated with: – A 5.5% mortality after CABG or MVR – A 11.6% 30-day postoperative mortality in patients who have pre-operative cirrhosis • Acalculous cholecystitis mortality can reach 70% (1,5)[A]

ETIOLOGY/RISK FACTORS

• Pre-existing liver disease: Viral hepatitis, cirrhosis, alcoholic hepatitis, mononucleosis, or congenital disorders • Major blood loss requiring blood transfusions • Prolonged hypotension in surgery • Medications: Erythromycin, chlorpromazine, halothane, enflurane, sulfonamides, penicillin, phenytoin, methyldopa, acetaminophen, methyltestosterone, rifampin, isoniazid, and nitrofurantoin • Hemolytic blood diseases: Sickle cell, thalassemias, G6PD deficiency, autoimmune anemia • Mechanical heart valves • In cardiac surgery: Prolonged bypass, aortic cross clamping; intra-aortic balloon pump use; pre-operative hepatic dysfunction due to heart failure; and type of surgery • Total parenteral nutrition (TPN): Short-term use can cause fatty liver and cholestasis, whereas long-term use can result in steatohepatitis, cholestasis, and acalculous cholecystitis • Acalculous cholecystitis: Male; major surgery including cardiac and GI, trauma, burns, renal failure; mechanical ventilation with positive end expiratory pressure (PEEP); TPN for at least 3 months; and critically ill patients

PHYSIOLOGY/PATHOPHYSIOLOGY

• Heme is a prosthetic group with an iron atom in the center of a porphyrin group. It is most commonly found in hemoglobin molecules within red blood cells. – Normal breakdown of hemoglobin occurs in reticuloendothelial cells with unconjugated (indirect) bilirubin byproduct. – Unconjugated bilirubin is water insoluble, binds readily to albumin, and is conjugated with glucuronic acid in the liver. – Conjugated (direct) bilirubin is water soluble and excreted in bile and urine. Normal lab values: Total bilirubin: 0.2–1.9 mg/dL Direct bilirubin: 0–0.3 mg/dL Indirect bilirubin: 0.2–0.7 mg/dL • Jaundice is the clinical manifestation of hyperbilirubinemia and describes a yellow pigmentation of the skin, sclera, and mucus membranes. • Pre-hepatic causes of postoperative jaundice result from increased red blood cell breakdown and unconjugated bilirubin levels. This can overwhelm the liver’s capacity to conjugate bilirubin. Perioperatively, this can result from: – Hemolysis (the rupture and release of hemoglobin) can result from blood transfusions, hemolytic diseases, mechanical heart valves, cardiac surgery. – Hematoma resorption • Intrahepatic causes of postoperative jaundice result in a reduced ability to conjugate bilirubin. Perioperative causes include hepatocellular injury (ischemia, medications, viral) or pre-existing liver disease. – Ischemic injury may result from cardiogenic or noncardiogenic shock, hypoxemia, or surgical injury (hepatic artery ligation, post-liver transplant) – Medications, TPN, and volatile agents – Viral infections can present after 3 weeks of surgery. In 2001, the Centers for Disease Control and Prevention reported the risk of hepatitis C infection from a unit of transfused

blood in the US to be less than one per million transfused units. – Pre-existing liver disease that was not recognized until after surgery is also possible. For example, unrecognized cholestatic liver disease such as primary sclerosing cholangitis or primary biliary cirrhosis. Gilbert’s syndrome, which is the most common inherited cause of unconjugated hyperbilirubinemia, is another possibility. • Posthepatic causes of postoperative jaundice result from an inability to excrete conjugated bilirubin. Intrahepatic and extrahepatic causes can result in the obstruction of bile flow or cholestasis. – Intrahepatic cholestasis can be caused by benign postoperative cholestasis, acalculous cholecystitis, sepsis, or medication induced. – Extrahepatic cholestasis can be caused by choledocholithiasis, cholecystitis, acalculous cholecystitis, upper abdominal surgery, postoperative pancreatitis, postoperative bile duct injury, stricture or tumor, or unrecognized liver diseases like primary sclerotizing cholangitis. • Postoperative abnormal LCTs in normal individuals may be due to decreased hepatic blood flow or the surgical procedure.

PREVENTATIVE MEASURES

• Do not perform elective surgery in cirrhotic or acute viral hepatitis patients (5)[B]. • Avoid TPN or blood transfusions when possible. • Avoid halothane. • Avoid using same syringes or multidose vials on patients to prevent infectious disease spread such as hepatitis. • Avoid severe hypotension.

PREOPERATIVE ASSESSMENT • Is based upon clinical and intraoperative history with laboratory results confirming the diagnosis. • Bilirubin overproduction (pre-hepatic) presents with elevated unconjugated bilirubin levels. It may also result in: – Elevated reticulocyte count – Low haptoglobin – Presence of schistocytes – Elevated AST and LDH (alkaline phosphatase and ALT are not largely elevated) (5)[B] • Decreased conjugation from hepatocellular injury presents with elevated unconjugated bilirubin levels. It may also result in: – Elevated aminotransferases (5–100 times normal) – Elevated LDH – Elevated alkaline phosphatase (2 times normal). – Positive viral hepatitis A and B serologies, hepatitis C RNA by PCR; elevated ALT and AST up to 10 times normal, LDH and alkaline phosphatase (small increases). – Halothane hepatitis presents with fever, arthralgias, skin rash, eosinophilia, repeated exposure to halothane • Decreased bilirubin excretion presents with elevated conjugated bilirubin. It may also result

in: – Elevated alkaline phosphatase (3 times normal) – Acholic stools – Pruritus – Biliary strictures, bile leaks, retained common bile duct stones can present with epigastric or right upper quadrant pain, fever, and jaundice – Acalculous cholecystitis demonstrates increased gallbladder wall thickness on ultrasound >4 mm, no response to cholecystokinin (CCK), intramural gas, and sloughed mucosal membrane (1)[A].

Pregnancy Considerations

Consider preeclampsia or acute fatty liver of pregnancy (AFLP) as possible diagnosis.

TREATMENT • Defer all other elective procedures • Discontinue medication if suspected to be drug-induced. • In cholestasis, consider open or laparoscopic cholecystectomy or antibiotics, endoscopic or radiologic interventions, or antibiotics. If seriously ill or unstable, percutaneous cholecystostomy can be done (1)[A]. Consider Vitamin K when severe disease is causing elevations in PT. • In hepatic hypoperfusion, consider invasive BP monitoring with an arterial line to avoid further hepatic hypoperfusion. • In hypersensitivity-drug-related liver injury, consider corticosteroids. • In fulminant hepatic failure, consider liver transplantation • Elevated LCTs in otherwise normal patients may be observed without intervention. However, if severe and getting worse, consider a hepatology consult CLOSED CLAIMS DATA

• Halothane hepatitis: 38 claims – Halothane plus patient with underlying condition: 2 claims – Halothane plus a hepatotoxic chemo: 1 claim – Of all 41 cases, 3 occurred after 1990, most recent was 1997 – 20 patients (49%) with halothane hepatitis died • Infectious hepatitis: 2 claims – Hepatitis B from reusing syringes for skin wheel – Hepatitis C from reusing multidose vial (at least 41 patients in the claim)

REFERENCES

1. Molina EG, Reddy KR. Postoperative jaundice. Clin Liver Dis. 1999;3:477–488. 2. Mastoraki A, Karatzis E, Mastoraki S, et al. Postoperative jaundice after cardiac surgery. Hepatobiliary Pancreat Dis Int. 2007;6:383–387. 3. Hsu RB, Lin FY, Chen RJ, et al. Incidence, risk factors, and prognosis of postoperative

hyperbilirubinemia after heart transplantation. Eur J Cardiothorac Surg. 2007;32:917–922. 4. Ziser A, Plevak DJ. Morbidity and mortality in cirrhotic patients undergoing anesthesia and surgery. Anesthesiology. 1999;90:42–53.

5. Faust TW, Reddy KR. Postoperative jaundice. Clin Liver Dis. 2004;8:151–166.

ADDITIONAL READING

• Barash PG, Cullen BF, Stoelting RK. Clinicial Anesthesia, 5th ed. Chapter 39: Anesthesia and the liver. New York, NY: Lippincott Williams and Wilkins, 2006. • www.asaclosedclaims.org See Also (Topic, Algorithm, Electronic Media Element) • Cholecystectomy • Blood transfusions

CODES ICD9

• 782.4 Jaundice, unspecified, not of newborn • 997.49 Other digestive system complications ICD10 • K91.89 Oth postprocedural complications and disorders of dgstv sys • R17 Unspecified jaundice

CLINICAL PEARLS

• Perform a thorough history and physical examination with a focus on surgical causes, intraoperative ischemic events, drugs, and pre-existing liver disease • Consider ordering an ultrasound of the right upper quadrant to rule out acalculous cholecystitis (high mortality). • Avoid halothane when possible.

POSTOPERATIVE NAUSEA AND VOMITING (PONV) Christine E. Goepfert, MD, PhD, DESA

BASICS DESCRIPTION

• Postoperative nausea and vomiting (PONV) is still a leading adverse event and more distressing for patients than postoperative pain • PONV is multifactorial in its origin, as a consequence of emetogenic triggers (such as inhaled anesthetics, opioids) to susceptible patients (women, history of motion sickness and PONV, non-smokers, long surgery). EPIDEMIOLOGY Prevalence

Can reach up to 80% Prevalence

Females are 3 times more likely, with up to 80%, to develop PONV Morbidity

Vomiting can result in rare, but potentially severe issues such as retinal detachment, suture dehiscence, wound bleeding, aspiration, subcutaneous emphysema, or esophageal rupture Mortality

Not proven

ETIOLOGY/RISK FACTORS

• General anesthesia (GA) with volatile agents and opioids (most common) remain the most relevant known causes. • Risk factors and independent predictors: – Women, until high age, independent of anesthesia technique (strongest predictor) – Non-smoking (1.8 times more likely) – History of PONV and/or motion-sickness – Young age: Children >3 years, adolescents, young adults independent of gender – Increased duration of anesthesia – Postoperative opioid use • Associated, evidence-based parameters: – Weakly associated: Anxiety – Unlikely associated: High FiO2, ginger

• NOT associated, evidence-based parameters (against individual impressions): Obesity, facemask ventilation, use of nasogastric or orogastric tube, IV use of neostigmine, phase of menstrual cycle, weather, and the phase of the moon.

• Regional anesthesia: Neuroaxial blockade and peripheral nerve blocks have more than a 4fold lower incidence of PONV. Risk factors and independent predictors include: Female gender, history of motion sickness, preoperative tachycardia, preoperative IV opioids, intrathecal procaine, use of phenylephrine or epinephrine, hypotension or high intrathecal block above T4.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Chemoreceptor trigger zone. Located in the area postrema at the bottom of the 4rd ventricle. Receives afferent input from various peripheral and central emetogenic neurons in response to toxic materials in the GI lumen, smell and sight, drugs (opioids), and toxins. • Nucleus tractus solitarius receives input from vestibular and GI vagal afferents, as well as the cortex, cerebellum, and vagal and glossopharyngeal nerves. The vestibular system is stimulated by motion and possibly by anesthetics and opioids. The cortex is influenced by emotions, pain, anticipation, and personality. • Lateral reticular formation of the medulla oblongata coordinates vomiting in the medulla and functions as the vomiting center. • The reason that PONV is high in women and remains elevated until advancing age remains unknown. It is obviously independent from the patient’s menstrual cycle. • Nicotine stimulates indirect GABA-mediated cerebral dopamine release, and nicotine withdrawal may lead to low postoperative cerebral dopamine levels, reducing activation of dopaminergic circuits in the CRTZ. • Children <3 years old do not suffer PONV; the risk becomes very high in adolescents and young adulthood. In men, the incidence of PONV decreases with age. The reasons for this effect remain speculative. • Longer and more complex surgeries lead, accordingly, to more PONV, depending on the administration of volatile anesthetics and intraoperative opioids. The type of surgery is not an independent predictor for PONV; however, the underlying conditions are, such as gender, length of surgery, volatile anesthetics, and intraoperative opioids. With maybe the exception of strabismus surgery in children, there is only an assumed association between different types of surgery and PONV. • Opioids: – Preoperative opioids: Few studies, irrelevant. – Intraoperative opioids: Dose, and not type, of opioid is relevant for causing PONV. – Postoperative opioids: Doubles the risk of PONV; dose, and not type, of opioids is relevant. • Propofol possesses antiemetic properties, with a dose-dependent effect: Anesthetic doses are most effective. • Inhalational anesthetics strongly lead (dose-dependently) to PONV. There is no difference between the volatile agents isoflurane, enflurane, sevoflurane and desflurane. • Nitrous oxide weakly contributes to PONV and is additive to the effects of volatiles.

PREVENTATIVE MEASURES

• Risk scores. The patient’s baseline risk is the main determinant of the effectiveness of antiemetic interventions. A simplified risk score by Apfel, Koivuranta et al. identifies 4 predictors: Female gender, history of motion sickness and/or PONV, nonsmoking status, and use of postoperative opioids. If 0, 1, 2, 3, or 4 of these risk factors are present, the

incidences of PONV over 24 hours in inpatients are 10%, 20%, 40%, 60%, and 80%. – Prophylaxis in low risk patients (1 risk factor, risk score <10%): Prophylaxis is rarely justified. The risks of treatment (sedation, headache, low BP, QT prolongations, Torsades de pointes etc.) should be weighed against the patient’s preference and medical concerns due to vomiting (e.g., a middle-aged male smoker having a microlaryngoscopy). – Moderate risk patients (2–3 risk factors, risk score 20–40%): Consider 1 or 2 antiemetic drugs or measures (e.g., total intravenous anesthesia [TIVA] with opioid and no other antiemetic drugs, or 4 mg of dexamethasone and block to minimize opioid consumption). An example is a middle-aged, non-smoking female with no other known risk factors undergoing an appendectomy. – High-risk patients (>3 risk factors, risk score >60%): Consider combination treatment (e.g., regional anesthesia instead of GA, or TIVA with additional antiemetic). An example is a young non-smoking female undergoing a craniectomy for the removal of a brain tumor. • Treatment guidelines suggest that outpatients should receive longer acting antiemetic measures. • Different mechanisms of antiemetic strategies have additive effects.

PREOPERATIVE ASSESSMENT • Nausea: Feeling of urge to vomit with sickness of the stomach, which can be measured with a VAS. • Vomiting: Expelling stomach contents through the mouth and nose.

DIFFERENTIAL DIAGNOSIS

Differentiate between nausea and vomiting due to anesthesia and other causes related to surgery or medical conditions; for instance, increased intracranial pressure, ileus, long fasting period, pre-existing nausea and vomiting due to chemotherapy (CINV).

TREATMENT • Although it is often self-limiting, PONV decreases patient satisfaction significantly • D2 antagonists may be used prophylactically as well as acutely for PONV

– Metoclopramide (benzamide) 25–50 mg IV: Extrapyramidal side effects (dystonia, akathisia, dysphoria, anxiety, restlessness) can occur in up to 0.8%. – Droperidol (butyrophenone) 0.625–1.25 mg IV: Dose-dependent side effects include sedation, extrapyramidal side effects. The FDA issued a Black Box Warning due to the potential for lethal arrhythmias, including Torsades de pointes, under low dose droperidol. Prior to administration, a 12-lead EKG should be performed and avoided in females with a QTc >450 ms and in males with a QTc >440 ms. It should be noted that other anesthetics generally have a more pronounced effect on QTc prolongation – Haloperidol (butyrophenone) 1–2 mg IM: IV use is off-label in the US. • Histamine (H1) antagonists can cause sedation, potentially leading to delayed awakening. – Diphenhydramine 25 mg IV: Acts on H1 receptor antagonists in the nucleus tractus

solitarius, other vomiting centers, and the vestibular system. It also functions as a weak anticholinergic. – Cyclizine 50 mg IV, promethazine 25 mg IV: Are non-specific antihistamines and equally potent anticholinergics; they are thus contraindicated in glaucoma and prostate hypertrophy. Side effects include urinary retention, blurred vision, dry mouth, and very rarely extrapyramidal side effects. • Anticholinergics: Central, muscarinic receptor antagonist – Atropine: Since it crosses the BBB, it has effects on PONV. However, it is less effective due to its short half-life. – Scopolamine TDS 1 mg/24 hr: Transdermal application as a patch effective up to 72 hours. Side effects include visual disturbances, dilated pupils, dry mouth, dizziness and agitation, particularly if rubbing the patch and touching their eyes. • Steroids: Dexamethasone 4–5 mg IV acts on the central inhibition of the nucleus tractus solitarii, but not the area postrema. It is commonly administered after induction as it can have severe and intense rectal burning and is slow in onset (commonly used prophylactically) • Serotonin (5-HT3) antagonists are the most popular class of prophylactic antiemetic drugs. They appear to act on all levels of central structures involved in PONV. They are associated with QTc prolongation and cardiac arrhythmias. – Ondansetron 4 mg IV has a plasma half-life of 4 hours. – Tropisetron 2 mg IV: QTc prolongation is observed only in high doses up to 80 mg IV. – Dolasetron 12.5 mg IV is the minimum effective dose; 50 mg is the equipotent of ondansetron. The plasma half-life is nearly twice as long as ondansetron. – Granisetron 1 mg IV (lower doses of 0.1 mg have also been shown to be effective). Similar plasma half-life to dolasetron. • Neurokinin (NK1) antagonists act on vagal afferents in the GI tract and in the area postrema; they are competitive inhibitors of substance P – Aprepitant 40 mg PO is effective against vomiting, but not nausea – Other NK antagonists in development: Casopitant and rolapitant; IV fosaprepitant is only approved for CINV • Miscellaneous drugs – Mirtazapine 30 mg PO for premedication reduces PONV through reduction of anxiety – Opioid antagonists have efficacy due to reduction of delay in gastric emptying. Naloxone 0.25 μg/kg/hr has been shown to be superior to placebo • Alternative remedies and approaches: – Ginger: Studies have not shown clear evidence for efficacy. – Liberal crystalloid fluid supplementation: May be of benefit for late onset PONV, potentially due to the lower need to drink early after surgery. – P6-stimulation of “nei guan” point via acupressure, acupuncture, transcutaneous nerve stimulation, laser stimulation, or acu-stimulation device: evidence for efficacy on PONV, especially in high-risk patients

FOLLOW-UP

• Rescue treatment strategies need to be started early to improve outcomes (e.g., time to discharge). Preferred pharmacologic rescue treatments include: – Serotonin antagonists are the first choice, if not given in the OR before – Dexamethasone – Antidopaminergics – Stimulation of P6 acupressure point – Scopolamine TDS – Non-opioid analgesics, such as NSAIDs – It is more effective to choose an alternative acting antiemetic to the one previously given. • Regional techniques such as peripheral nerve blocks or catheter techniques, to spare oral or IV opioids for postoperative pain control.

CLOSED CLAIMS DATA

PONV is not mentioned in the 2011 Closed Claims’ Analysis

REFERENCES

1. Apfel CC, et al. A simplified risk score for predicting postoperative nausea and vomiting: Conclusions from cross-validations between two centers. Anesthesiology. 1999;91(3):693– 700. 2. Carpenter RL, et al. Incidence and risk factors for side effects of spinal anesthesia. Anesthesiology. 1992;76(6):906–916. 3. Eberhard LH, et al. The development and validation of a risk score to predict the probability of postoperative vomiting in pediatric patients. Anesth Analg. 2004;99(60):1630–1637. 4. Fero KE, et al. Pharmacologic management of postoperative nausea and vomiting. Expert Opin Pharmacother. 2011;12(15):2283–2296. 5. Pierre S, et al. A risk score-dependent antiemetic approach effectively reduces postoperative nausea and vomiting – a continuous quality improvement initiative. Can J Anaesth. 2004;51(4):320–325. 6. Apfel CC, et al. Transdermal scopolamine for the prevention of postoperative nausea and vomiting: A systematic review and meta-analysis. Clin Ther. 2010;32(12):1987–2002. 7. Lee A, Fan LTY. Stimulation of the writs acupuncture point P6 for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev. 2009;15:CD003281. • Wallenborn J, et al. The impact of isoflurane, desflurane, or sevoflurane on the frequency and severity of postoperative nausea and vomiting after lumbar disc surgery. J Clin Anesth. 2007;19(3):180–185.

CODES ICD9 • 787.01 Nausea with vomiting • 997.49 Other digestive system complications

ICD10

• K91.89 Oth postprocedural complications and disorders of dgstv sys • R11.2 Nausea with vomiting, unspecified

CLINICAL PEARLS

• An underappreciated risk factor for PONV is the length of surgery. • The most effective antiemetic strategy would be to avoid emetogenic triggers, which are GA with volatile agents and opioids, and perform opioid-free regional anesthesia instead. • If a GA needs to be done in very susceptible patients, a TIVA with or without additional antiemetic strategies is advisable. • PONV properties of opioids seem to depend on the (equipotent) dose, not on type of opioid. • The risk of PONV in local and regional anesthesia is not 0%; it is, however, at least 4 times lower compared to general anesthesia. • No available antiemetic strategy will completely eliminate PONV. In very high-risk patients, multimodal therapy with independently acting measures and drugs should be chosen.

POSTOPERATIVE PULMONARY COMPLICATIONS (PPCS) Kalpana Tyagaraj, MD

BASICS DESCRIPTION

Postoperative pulmonary complications (PPCs) are as common as cardiac complications for patients undergoing non-cardiothoracic surgery. Similarly, they contribute to morbidity, mortality, and length of stay. EPIDEMIOLOGY Prevalence

5–10% of all surgical patients experience PPCs. Morbidity

The most significant PPCs are: Atelectasis, pneumonia, respiratory failure, and exacerbation of underlying chronic lung disease. Mortality

Following abdominal aortic aneurysm (AAA) repair, patients who develop postoperative respiratory failure (PPF) have an in-hospital mortality that reaches 40–42% (compared to 6% for those without). ETIOLOGY/RISK FACTORS

Patient-related risk factors • Age: Appears to be an independent, significant risk factor. In a study of patients older than 80 years, the overall 30-day mortality rate was 6.2%. As age is obviously a nonmodifiable risk factor, and the potential risk of complications does not invariably translate into increased mortality, surgery should not be declined because of advanced age alone. • Chronic obstructive pulmonary disease (COPD): The most common risk factor. Patients with severe COPD (forced expiratory volume in 1 second [FEV1] <40% predicted) are 6 times more likely to have a major postoperative complication. Despite the increased risk, a prohibitive level of pulmonary function for an absolute contraindication is not apparent. The benefits of surgery must be weighed against these complications. A careful preoperative evaluation should include identification of high-risk patients and aggressive treatment. Elective surgery should be deferred in symptomatic patients with poor exercise capacity or having an acute exacerbation. • Cigarette use: Patients who currently smoke have a 2-fold increased risk even in the absence of COPD. The risk is highest in patients who smoked within the last 2 months. Patients who quit smoking for more than 6 months have a risk similar to those who do not smoke. The risk of postoperative pneumonia appears to remain elevated up to 1 year after smoking cessation.

• ASA classification: The incidence of PPC increases with comorbidities. Class I: 1.2%; Class II: 5.4%; Class III: 11.4%; Class IV: 10.9% • Obesity (BMI > 30): Causes a reduction in lung volume, V/Q mismatch, and relative hypoxemia that are accentuated after surgery. In severe cases, pulmonary hypertension, cor pulmonale, and hypercapnic respiratory failure (“pickwickian" syndrome) are seen. • Asthma: Increases the risk of bronchospasm, hypoxemia, hypercapnia, inadequate cough, atelectasis, and pulmonary infection following surgery. Inadequate preoperative control may increase the risk. • Obstructive sleep apnea (OSA): Patients are at increased risk of developing deterioration of breathing, severe hypoxemia, and hypercapnia in the postoperative period. Obese patients with sleep apnea may present difficulties with endotracheal intubation or early postoperative upper airway obstruction, requiring reintubation or other therapies.

Procedure-related risk factors • Surgical site: The incidence of PPC is inversely related to the distance of the surgical incision from the diaphragm. The complication rates for thoracic surgery range from 19–59%, upper abdominal surgery 17–76%, and lower abdominal surgery 0–5%. AAA repair is associated with the highest risk. • Duration of surgery: Patients undergoing procedures lasting longer than 3–4 hours have a higher incidence rate (40%) compared to procedures less than 2 hours (8%). • Anesthetic technique: General anesthesia (GA) appears to be associated with a higher risk of clinically important complications compared with epidural or spinal anesthesia. The associated mechanisms appear to be GA-associated respiratory changes, residual effects of sedatives, narcotics and neuromuscular blockers. The duration of anesthesia also correlates with PPC. • Emergency surgery: The limited time available to implement protective strategies (e.g., intensive preoperative inspiratory muscle training) increases the incidence of PPC. PHYSIOLOGY/PATHOPHYSIOLOGY

• Intraoperative changes: Many PPCs are related to the disruption of normal respiratory muscle activity which begins at the time of induction and continues into the postoperative period. The lack of coordinated activity decreases efficiency and impaired functional residual capacity (FRC) causes atelectasis. Of note, chest wall distortion and atelectasis is more pronounced with mechanical ventilation. – Volatile and intravenous drugs affect the central regulation of breathing. The altered neural drive to respiratory muscles results in respiratory depression. – Airway instrumentation can result in reflex stimulation and the release of inflammatory mediators with resultant bronchoconstriction. Increased airway resistance limits expiratory gas flow, which can produce hyperinflation with risk of barotrauma and abnormal gas exchange. – Tracheal intubation and anesthetic vapors impair mucociliary transport. – Prolonged anesthesia and surgery can impair the function of the inflammatory cells and cause postoperative infections. – Cardiopulmonary bypass can cause acute lung injury – Surgical trauma and barotrauma can cause pneumothorax

– Laryngospasm can cause negative pressure pulmonary edema – Aspiration of stomach contents can occur during induction and emergence, or intraoperatively with supraglottic devices or deep sedation • Postoperative changes: The role of surgical trauma is most pronounced after thoracic and abdominal surgery. Causes include the functional disruption of respiratory muscles (intercostals and abdominal muscles) by incisions; postoperative pain that limits voluntary respiratory motion; and visceral stimulation that can decrease phrenic motor neuron output and limit diaphragmatic descent. The persistent decrease in FRC and respiratory muscle function lasts for several days after surgery. Prolonged atelectasis can result in pneumonia. Even laparoscopic techniques can still stimulate abdominal viscera and affect pulmonary mechanics.

PREVENTATIVE MEASURES

• Preoperative risk assessment: A complete history and physical examination helps to identify risk factors for PPC. Seek any history of smoking, exercise intolerance, unexplained dyspnea, or cough. Note evidence of COPD, such as decreased breath sounds, wheezes, crackles, or a prolonged expiratory phase. Consider further workup as needed. – Pulmonary function tests (PFTs): Several retrospective studies of routine PFTs found only a marginal benefit in predicting postoperative complications, other than in those undergoing lung resection. Preoperative spirometry has not been shown to be predictive of complications following abdominal surgery. Thus, testing should be restricted to those patients with unexplained dyspnea or exercise tolerance, or undergoing resectional surgery. – Arterial blood gasses (ABGs): Measures of pH, PaO2, and PaCO2 may be utilized to

establish an objective baseline, or deviation from it. – Chest radiography: Studies suggest that it adds little to the clinical evaluation in healthy patients and routine preoperative evaluation is unnecessary. – Polysomnographic sleep study: In patients with sleep apnea, the diagnosis should be confirmed and the severity assessed with a sleep study. The severity is judged based on the apnea–hypopnea index and the lowest oxygen saturation value during sleep. • Multifactorial Risk Index for Predicting Postoperative Respiratory Failure: Developed and validated respiratory failure risk index from 44 VA medical centers. – Useful to evaluate the perioperative risk for developing PPF (defined as the inability to be extubated 48 hours after surgery); considered the most serious of thePPCs. – Operation-specific risk factors had the highest value, in particular, the type of surgery; however, the ability to intervene and decrease these factors is minimal. – Patient-related factors are amenable to treatment or optimization and play a role in decreasing the PPF risk. • Preoperative strategies to reduce PPC: – Smoking cessation for 8 weeks – Proper perioperative fluid management – Correction of possible malnutrition – Pulmonary rehabilitation – Educate patients on lung expansion maneuvers and inspiratory muscle training

– Antibiotic therapy for acute bronchitis. • Intraoperative strategies to reduce PPC: – Intermediate and short-acting neuromuscular blocking agents – Regional anesthesia when feasible – In extremely high-risk patients, less invasive, shorter or modified procedures should be considered. – When possible, laparoscopic procedures should be substituted for open procedures. – In patients with known or possible sleep apnea, the perioperative use of sedatives and narcotics should be minimized. • Postoperative strategies to reduce PPC: – Lung expansion maneuvers (incentive spirometry, deep breathing exercises, intermittent positive pressure breathing [IPPB], continuous positive airway pressure [CPAP]), postural drainage, percussion and vibration, coughing, suctioning, and mobilization. – Pain control: Adequate postoperative pain control helps minimize pulmonary complications by facilitating earlier ambulation and lung expansion. In upper abdominal procedures, epidural analgesia had lower rates of pulmonary complications and a shorter hospital stay. Epidural narcotics provide a longer duration of action, a lack of excessive sedation and respiratory depression, and a minimum or absence of sensory motor loss. – Good glycemic control: Associated with a reduced duration of mechanical ventilation; however, its specific impact on PPCs is unclear – Nasogastric decompression: Selective use of nasogastric tubes in patients with postoperative nausea and vomiting (PONV), inability to tolerate oral intake, or symptomatic abdominal distention may be appropriate. However, the routine use following abdominal surgery is associated with higher rates of pneumonia. – Total parenteral nutrition: Although poor nutrition is a risk factor for PPC, the routine use of total parenteral nutrition has no benefit over enteral nutrition or no hyperalimentation, except in patients with severe malnutrition or prolonged inadequate enteral feeding. – Prevention of venous thromboembolism (VTE): Surgery is a well-recognized risk factor for the development of deep vein thrombosis and pulmonary embolism. The risk is influenced by patient and procedure-related factors; appropriate thromboprophylaxis is essential in high-risk patients. See Table

REFERENCE

1. ong W, Weber E. Factors associated with postoperative pulmonary complications in patients with severe COPD. Anaesth Analg. 1995;80:276–284. 2. Arouzullah A. Multifactorial risk index for predicting postoperative respiratory failure in men after major noncardiac surgery. Ann Surg. 2006;232:242–253. 3. Lawrence V. Strategies to reduce postoperative pulmonary complications after noncardiothoracic surgery: systematic review for the American College of Physicians. Ann Int Med. 2006;144:596–608.

ADDITIONAL READING

• www.emedicine.medscape.com - perioperative pulmonary management See Also (Topic, Algorithm, Electronic Media Element) • Atelectasis • Hypoxia, postoperatively • Asthma • Obstructive sleep apnea • Geriatric physiology

CODES ICD9

• 518.0 Pulmonary collapse • 997.32 Postprocedural aspiration pneumonia • 997.39 Other respiratory complications ICD10 • J95.2 Acute pulmonary insufficiency following nonthoracic surgery • J95.821 Acute postprocedural respiratory failure • J95.89 Oth postproc complications and disorders of resp sys, NEC

CLINICAL PEARLS

• PPCs contribute significantly to overall perioperative morbidity and mortality rates. • The goal of perioperative pulmonary management is to identify patients at high risk for significant postoperative pulmonary complications, so that appropriate interventions can be implemented in order to minimize that risk.

POSTOPERATIVE RENAL DYSFUNCTION Patrick Kim, MD Selma Ishag, MB, BS, MD

BASICS DESCRIPTION

• Acute kidney injury (AKI) is a frequently encountered postoperative complication with significant short-term and long-term consequences. • The Acute Kidney Injury Network classifies AKI as: – Stage 1: Increase in SrCr >0.3 mg/dL or 1.5–2-fold increase from baseline, or urine output (UOP) <0.5 mL/kg/hr × 6 hours – Stage 2: 2–3-fold increase in SrCr, or UOP <0.5 mL/kg/hr × 12 hours – Stage 3: >3-fold increase in SrCr or an acute increase of >0.5 mg/dL in patients with a baseline SrCr >4 mg/dL, or UOP <0.3 mL/kg/hr × 24 hours or anuria × 12 hours; or patients requiring renal replacement therapy (RRT) • Despite being the basis of the AKI definition, SrCr is not a very sensitive marker of the condition: – Changes in GFR are reflected by SrCr levels 2–3 days after an insult. – Levels vary with the patient’s age, body habitus, and volume status. • Newer biomarkers of AKI are being developed: – Neutrophil gelatinase-associated lipocalin (NGAL). A protein is upregulated by tubular endothelial cell after an ischemic injury. Urinary and plasma levels are being studied. – KIM-1: Transmembrane protein that is highly expressed by de-differentiated tubular cells following injury. – Cystatin C: Produced by all nucleated cells. It is freely filtered and completely reabsorbed and degraded by the tubules. Reflects glomerular filtration, not tubular injury. Value not yet certain but could identify AKI before elevations of creatinine occur. – IL-18: Tubular epithelial pro-inflammatory cytokine that gets activated in proximal tubules following injury. May be a predictor of mortality in critically ill patients. EPIDEMIOLOGY Prevalence

• Difficult to ascertain due to the previously widely varying definitions of acute renal failure in the literature. • Varies widely depending on the surgery. Estimated at 1% in major non-cardiac surgery and up to 25% in cardiovascular surgery patients Prevalence

Varies according to patient population. Occurs in approximately 5–7% of hospitalized patients and 30–35% of ICU patients.

Morbidity

Significant: Postoperative acute renal failure is associated with an increased risk of perioperative infection, longer ICU and/or hospital stay, need for renal replacement therapy (RRT), and acceleration of coronary vascular disease with increased long-term morbidity. Mortality

Significant: Patients with an increase in serum creatinine by 2 mg/dL or who require hemodialysis have an 8-fold increase in 30-day mortality. Even a modest increase in SrCr >0.5 mg/dL in hospitalized patients is associated with a 6.5-fold increase in the odds of inhospital death. ETIOLOGY/RISK FACTORS

• High risk surgical procedures include: Cardiac and vascular surgery, heart and liver transplant, hepatobiliary surgery, and procedures utilizing radiocontrast • High risk patients include: – Renal insufficiency, both mild and moderate – Ascites – Active congestive heart failure – Emergency surgery – Age >56 years – Diabetes mellitus – Hypertension – Male sex

PHYSIOLOGY/PATHOPHYSIOLOGY

• Total renal blood flow (TRBF) is about 20% of the cardiac output with an oxygen delivery of 80 mL/min/100 g of tissue. • The renal cortex receives most of the TRBF and has a low oxygen extraction ratio (∼20%). • The renal medulla has a smaller blood flow and a high oxygen extraction ratio (∼80%), consequent to the high metabolic demand of tubular reabsorptive function. Thus, the renal medulla is susceptible to ischemic insults. • In acute tubular necrosis (ATN), ischemia and/or direct toxicity result in apoptosis and shedding of tubular cells as well as recruitment of vasoactive and inflammatory mediators that worsen ischemic injury. Loss of tubular cells allows leakage of glomerular filtrate into the interstitium which results in edema that may progress to chronic inflammation and fibrosis, ultimately leading to chronic kidney disease. • Perioperatively, a combination of factors contribute to renal dysfunction: – Preoperatively: Hypovolemia due to preoperative fasting, bowel preparation – Intraoperatively: Effect of anesthetics on hemodynamics and renal perfusion, effect of surgical technique on renal blood flow (e.g., laparoscopic procedures), blood loss, neuroendocrine response to anesthesia and surgery, excessive fluid resuscitation – Use of nephrotoxins such as contrast media, antibiotics, NSAIDs, etc.

PREVENTATIVE MEASURES

• The cornerstone of treatment is prevention.

• Pharmacologic interventions have been controversial, and as of yet, no pharmacologic interventions have definitively been beneficial in the prevention of renal failure in the perioperative period with the exception of mannitol administration prior to renal transplant reperfusion. • Maintain adequate blood pressure. – Autoregulation maintains a constant renal blood flow between mean arterial pressures (MAPs) of 80–160 mm Hg. – Improved renal hemodynamics has been shown with MAPs around 75 mm Hg. – The autoregulation curve may be shifted to the right in chronic hypertensives, so higher pressures may be needed. • Ensure euvolemia. – Oxygen delivery to the kidneys may be reduced in hypovolemia, resulting in ischemic ATN. – Excessive fluid resuscitation may lead to abdominal compartment syndrome (intraabdominal hypertension [IAH]) and impaired renal perfusion. – Normal saline given in volumes >30 mL/kg can cause a non-gap hyperchloremic metabolic acidosis and hyperkalemia. Hyperchloremia may result in a decrease in renal blood flow, glomerular filtration rate, and urine output. – Albumin may not be more beneficial than crystalloids except in specific situations such as in cirrhotic patients with spontaneous bacterial peritonitis. – There is conflicting evidence on the renal safety of hydroxyethyl starch. • Optimize the oxygen delivery to the kidneys by maintaining an adequate hemoglobin level and cardiac output. • Avoid nephrotoxins. – Iodinated contrast agents are being used with increasing frequency and can cause contrast induced-acute kidney injury (CI-AKI). In addition to being directly toxic to tubular cells, they can cause renal vasoconstriction. Unfortunately at this time, no definitive technique has been shown to consistently decrease or eliminate this risk. The following may be considered: Adequate hydration to a goal of 100–150 mL/hr of UOP to potentially “wash off” the agent and minimize contact time with tubular cells; antioxidants such as N-acetyl cysteine, statins, and urine alkalinizers such as sodium bicarbonate may reduce free radical-related tubular cell apoptosis; the use of low osmolar agents (approximately twice the osmolarity of plasma) in normal patients and iso-osmolar agents in patients at risk of CI-AKI; avoid concomitant use of other nephrotoxins as well as repeat exposure (within 72 hours) of receiving a contrast medium load. – NSAIDs inhibit vasodilatory prostaglandins and can result in decreased glomerular filtration pressure by vasoconstricting afferent arterioles. Consider avoiding in high-risk patients. However, in one study, no long-term impairment in renal function was found when given postoperatively to kidney donors. – ACEI and ARBs: Decrease glomerular filtration pressure by vasodilating efferent arterioles. Avoid in hypovolemia. – Antibiotics such as aminoglycosides can cause ATN by accumulating in the proximal tubules. – Other nephrotoxins include antifibrinolytics such as aprotinin, immunosuppressants such

as cyclosporine and tacrolimus, and chemotherapeutic agents such as cisplatin.

PREOPERATIVE ASSESSMENT • History and physical examination including medication review, perioperative exposure to nephrotoxins, volume and hemodynamic assessment. • On urinalysis, hyaline casts suggest prerenal azotemia, whereas pigmented casts are seen in ATN. • Concentration of urine solutes and avid sodium retention is seen in prerenal azotemia. This will result in a specific gravity >1.015, osmolality >350 mOsm/kg, and urine sodium <20 mmol/L. • Fractional excretion of sodium (FENa) is helpful in distinguishing between prerenal azotemia and ATN. FENa levels <1% suggest prerenal azotemia and >3% suggest ATN; however, patients with prerenal azotemia treated with diuretics may have high FENa. • Fractional excretion of urea may be helpful in differentiating between prerenal azotemia and ATN. • Newer biomarkers such as NGAL and KIM-1 may play a role in distinguishing ATN from other causes of AKI. • Exclude urinary tract obstruction. – Renal ultrasound – High resolution CT scan of abdomen and pelvis

DIFFERENTIAL DIAGNOSIS

• Prerenal AKI results as a consequence of true hypovolemia or decreased effective circulating blood volume (as in cirrhosis, CHF). • Intrinsic AKI can be due to tubular, interstitial, or glomerular injury. – ATN is the most common cause of intrinsic AKI. It occurs as a result of ischemia (prolonged absolute or relative hypotension), exposure to nephrotoxins, and/or the endotoxins and inflammatory mediators released in septic patients. – Acute interstitial nephritis is infiltration of the interstitium by lymphocytes secondary to the use of NSAIDs or antibiotics. – Acute glomerulonephritis is characterized by rapid progression and may be seen in poststreptococcal infection or in the setting of endocarditis. • Postrenal AKI: Urinary tract obstruction can be seen perioperatively in pelvic surgery following inadvertent injury to the bladder or ureter(s). Intraoperative identification may include the use of intravenous methylene blue or indigo carmine.

TREATMENT • Mainly supportive • RRT may be initiated before the development of the classic indications of hyperkalemia, metabolic acidosis, volume overload, and symptomatic uremia. Controversy still exists on the best modality of RRT (continuous RRT or intermittent hemodialysis) and the dosing (intensity of dialysis).

FOLLOW-UP • Basic metabolic profile • Free excretion of sodium, urea • Urine specific gravity • Postoperative urinary output • 24-hour creatinine clearance

CLOSED CLAIMS DATA

Perioperative renal failure Closed Claims Data. There were 75 claims from 1978 to 2006: • Male: 53% • Age >53 years: 50% • ASA 3–5: 45% • Intraoperative oliguria or anuria: 31% • Emergency surgery (ASA classification): 29% • Vascular surgery: 16% • Cardiac surgery: 3% • Perioperative events leading to renal dysfunction/failure: – Patient condition or surgical cause: 17% – Wrong blood administered: 15% – Electrolyte imbalance or inappropriate fluid therapy: 13% – Medication error: 12% – Excessive blood loss: 8% • Outcome and liability: – Mortality: 47% – Substandard anesthesia care: 48% – Payments/settlement to patient: 56% – Median payment: $255,000 (range: $4,000–$3,625,000)

REFERENCES

1. agshaw SM, et al. Review article: Acute kidney injury in critical illness. Canadian J Anesth. 2010;57:985–998. 2. Kheterpal S, Tremper K, Heung M, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery. Anesthesiology. 2009;110:505– 515. 3. Crowley ST, Pexioto AJ. Acute kidney injury in the intensive care unit. Clin Chest Med. 2009;29–43. 4. Jones D, Lee H. Perioperative Renal Protection. Best Pract Res Clin Anesthesiol. 2008;22(1):193–208. 5. Khalil P, Murty P, Palevsky P. The patient with acute kidney injury. Prim Care Clin Office Pract. 2008;35:239–264. 6. Posner KL. Personal communication. ASA Closed Claims Project N8954, March 1, 2011.

ADDITIONAL READING

• Chertow MG, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005;16:3365–3370. • Friedwald VE, Goldfarb S, Laskey W, et al. The editor’s roundtable: contrast-induced nephropathy. Am J Cardiol. 2007;100(3):544–51. • Jarnberg P. Renal protection strategies in the perioperative period. Best Pract Res Clin Anesthesiol. 2004;18(4):645–660. • Sear JW. Kidney dysfunction in the postoperative period. Brit J Anesth. 2005;95(1):20–32. • Tang I, Murray P. Prevention of perioperative acute renal failure: what works? Best Pract Res Clin Anesthesiol. 2004;18(1):91–111.

CODES ICD9 • 584.9 Acute kidney failure, unspecified • 997.5 Urinary complications, not elsewhere classified ICD10 • N17.8 Other acute kidney failure • N99.89 Oth postprocedural complications and disorders of GU sys

CLINICAL PEARLS

• With the exception of maintaining adequate renal perfusion pressures and fluid hydration, there are not many interventions that can actively prevent renal failure postoperatively. • Low intraoperative urinary output is not always correlated with postoperative renal failure. • Oliguria during laparoscopic procedures is due to compression of the kidneys and their vessels by the pneumoperitoneum. It usually resolves after desufflation. Avoid insufflations pressures >15 mm Hg.

POSTOPERATIVE SHIVERING Jose M. Soliz, MD

BASICS DESCRIPTION

Postoperative shivering is involuntary, oscillatory muscle activity that augments heat production; it is common upon emergence from anesthesia. EPIDEMIOLOGY Prevalence

• Up to 40% of patients shiver during recovery after undergoing a general anesthetic (1) • Up to 30% of patients shiver during epidural anesthesia • The incidence of shivering is affected by the core body temperature: – At 35.5°C, up to 50% of patients shiver. – Between 34.5–35.4°C: Up to 90% of patients shiver. Morbidity

• Increases O2 consumption by up to 300%; as a result, it may increase the incidence of adverse myocardial events in high-risk patients. • Increases CO2 production

• Increases plasma catecholamine levels • Increases intraocular and intracranial pressures • Increases postoperative pain and discomfort • Hypothermia may exacerbate postoperative bleeding, prolong neuromuscular blockade, delay emergence, delay wound healing, and increase the risk of surgical site infection (1).

Mortality

May indirectly increase due to adverse cardiovascular events and increased risk of infection. Data is not currently available. ETIOLOGY/RISK FACTORS

• Most commonly occurs as a complication of hypothermia (2) • Normothermic shivering can also occur in: – Younger patients – Prolonged surgery – Orthopedic surgery

PHYSIOLOGY/PATHOPHYSIOLOGY

• The preoptic region of the hypothalamus is the dominant autonomic thermoregulatory center. When this region is cooled, shivering is believed to be mediated via recurrent inhibition of a group of inhibitory neurons called Renshaw cells. Shivering thus serves as a

normal, physiologic, protective mechanism to create warmth by energy expenditure. • Perioperative hypothermia – During general peripheral vasodilation results in redistribution of heat from the core to the periphery; this typically occurs over the first hour. – Heat loss from the patient to the environment/surroundings occurs via radiation, conduction, convection, and evaporation. • Anesthetic agents and shivering. During surgery, anesthetic medications increase the shivering threshold and protect against intraoperative shivering. However, as plasma concentrations decrease in the postoperative period, shivering can occur (8). • Neuraxial anesthesia and shivering. Spinal and epidural anesthetics produce sympathetic blockade with resultant vasodilation and heat loss. The mechanism of postoperative shivering is not fully understood. – Shivering is a function of motor activity; thus dermatomes that have motor blockade will not produce oscillatory muscle activity. – Spinal blocks initially decrease core temperature faster than epidural anesthesia; thus, the shivering threshold is achieved faster. • Non-thermoregulatory shivering: Shivering is not isolated to hypothermic states; the pathogenesis is not completely understood. Potential causes include: – The release of pyrogenic mediators elicited by surgical tissue damage – Anesthetic drugs – Postoperative pain – Decreased sympathetic activity – Uninhibited spinal reflexes/loss of descending control – Adrenal suppression – Fever – Respiratory alkalosis

Pediatric Considerations

• Neonates have an increased body surface area and are susceptible to hypothermia in the perioperative period. In addition, neonates cannot respond to cold stress by shivering; these mechanisms do not develop until the age of 6 months to 1 year. Measures to decrease heat loss and generate heat include: – Peripheral vasoconstriction via norepinephrine release: This can lead to pulmonary artery constriction and right-to-left shunting (hypoxia, cyanosis), as well as decreased tissue perfusion with subsequent tissue hypoxia and metabolic acidosis. – Non-shivering thermogenesis (NST): Describes the metabolism of brown fat which increases oxygen consumption and carbon dioxide production. The increased oxygen requirements may lead to hypoxia and metabolic acidosis; the increased carbon dioxide production may lead to tachypnea (if unable to adequately exhale the increased load, can result in respiratory acidosis). Furthermore, inhalational anesthetics inhibit brown fat metabolism, further increasing neonatal susceptibility to hypothermia in the operating room.

Pregnancy Considerations

Epidural meperidine, fentanyl, alfentanil, and morphine have been used to treat shivering in

the obstetric patient. Intravenous propofol has also been used to decrease cold responses. Shivering can also occur in the laboring patient who did not receive neuraxial anesthesia, which suggests a non-thermoregulatory mechanism for shivering during labor. PREVENTATIVE MEASURES

• Prevention of hypothermia is preferred to rewarming in the postoperative period (3). This can be facilitated by: – Intraoperative temperature monitoring: Core body temperature is measured in the distal esophagus, nasopharynx, tympanic membrane, or pulmonary artery. – Blankets and drapes to decrease radiation of heat into the cooler environment. – Forced air warming decreases the radiation of heat into the cooler environment as well as actively warms the patient. It is considered the most effective method. – Increasing the ambient temperature of the surgical suite decreases the radiation of heat into the environment – Warm intravenous fluids and blood products – Humidify anesthesia circuits

PREOPERATIVE ASSESSMENT Visualized cutaneous muscle contractions DIFFERENTIAL DIAGNOSIS

• Seizure • Muscle spasms from hypocalcemia, hypokalemia • Rigors in patients developing fever • Extrapyramidal symptoms in patients with Parkinson’s disease or Parkinson-like syndrome.

TREATMENT • Hypothermic shivering: Cutaneous warming with blankets or forced air in the recovery room. • Non-thermoregulatory (and hypothermic shivering, while simultaneously rewarming) can be treated with pharmacologic agents: – Meperidine 12.5 mg or 25 mg IV; via kappa receptor effects. – Granisetron 40 mcg/kg IV (5); via 5-HT3 activity. – Tramadol 0.1 mg/kg IV; via a modulatory effect on central monoaminergic pathways. It has the benefit of decreased sedation compared to meperidine (6). – Opioids (morphine, fentanyl); likely via analgesic effects. – Physostigmine 0.04 mg/kg IV; crosses the blood–brain barrier and is a cholinesterase inhibitor. Cholinergic stimulation of the hypothalamic–pituitary–adrenal axis and the adrenal medulla enhance the secretion of arginine vasopressin, epinephrine, and norepinephrine; these neurotransmitters are believed to be involved in body temperature control. Physostigmine is associated with bradycardia and gastrointestinal upset. – Ketamine 0.5 mg/kg IV prophylactically (7); mechanism via antagonism of the NMDA

receptor. – Clonidine 75 mcg IV; a centrally acting alpha-2 receptor agonist. May decrease blood pressure. – Chlorpromazine 10–20 mg IV; exact mechanism to reduce shivering is unknown. It may possibly occur via antidopaminergic or anticholinergic activity. – Doxapram 100 mg IV (3); centrally acts to increase the shivering threshold, may also have weak opioid receptor activity. – Dexmedetomidine 1 mcg/kg; likely via reduced central adrenergic flow.

FOLLOW-UP • If patients are hypovolemic, rewarming may cause vasodilatation leading to hypotension, reflex tachycardia, and myocardial ischemia. Replacing intravascular volume while rewarming may be necessary. • Opioid-related side effects can occur when used for the treatment of shivering. Monitor for respiratory depression, drowsiness, altered mental status, nausea, vomiting, and pruritus.

CLOSED CLAIMS DATA

Devices used to warm the patient’s skin resulted in 28 burns (N = 3000 total claims). 18 of the 28 were from IV fluid bags or water bottles applied directly to the patient’s skin. 5 of the 28 burns resulted from circulating water mattresses (4).

REFERENCES

1. Bhattacharya PK, Bhattacharya L, Jain R, et al. Post anesthesia shivering (PAS): a review. Indian J Anaesth. 2003;47(2): 88–93. 2. Leopold H, Eberhart J, Doderlein F, et al. Independent risk factors for postoperative shivering. Anesth Analg. 2005;101:1849–1857. 3. Kranke P, Eberhart LH, Roewer N, et al. Pharmacological treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials. Anesth Analg. 2002;94:453–460. 4. Cheney FW, Posner KL, Caplan RA, et al. Burns from warming devices in anesthesia. Anesthesiology. 1994;80:806–810. 5. Sajedi P, Yaraghi A, Moseli HA. Efficacy of graniesetron in preventing postanesthetic shivering. Acta Anaesthesiol Taiwan. 2008;46(4):166–170. 6. Tsai YC, Chu KS. A comparison of tramadol, amitryptyline, and meperidine for postepidural anesthetic shivering in parturients. Anesth Analg. 2001;93(5):1288–1292. 7. Sagir O, Guthas N, Toprak H, et al. Control of shivering during regional anesthesia: Prophylactic ketamine and granisetron. Acta Anaesthesiol Scand. 2007;51(1):44–49.

8. Horn EP. Postoperative shivering: Aetiology and treatment. Curr Opin Anaesthesiol. 1999;12(4):449–453.

ADDITIONAL READING

• Hypothermia • Surgical site infection • Chronic angina

CODES ICD9

995.89 Other specified adverse effects, not elsewhere classified ICD10

T88.51XA Hypothermia following anesthesia, initial encounter

CLINICAL PEARLS

• Prevention of hypothermia is key. • Intraoperative forced air warming is the most effective method of preventing hypothermia. • Various pharmacologic agents can be used as treatment. Meperidine (12.5 mg or 25 mg IV) is the most consistently effective.

POSTRENAL ACUTE KIDNEY INJURY Jonathan Anson, MD

BASICS DESCRIPTION

• Acute kidney injury (AKI) is a sudden decrease in kidney function causing acid–base imbalance along with fluid and electrolyte disturbances. • AKI causes can be divided into: – Prerenal – Intrarenal – Postrenal: Accounts for just 5–10% of all AKI, but is often easily reversible. • In the perioperative period, patients may present: – For temporary or definitive surgical treatment to relieve a pre-existing urinary obstruction – For pre-emptive stent placement prior to abdominal or pelvic surgeries – With anuria, oliguria, or signs and symptoms of AKI secondary to mechanical obstruction • The reversible nature of postrenal disease makes a prompt diagnosis essential.

PHYSIOLOGY PRINCIPLES

• Nephrons are the functional units of the kidney. – Afferent arterioles form glomerular capillaries within the Bowman’s capsule (cup-like structure). They exit via efferent arterioles after filtering into the nephron via hydrostatic forces. – Urine ultrafiltrate passes from the proximal convoluted tubule to the loop of Henle to the distal convoluted tubule and finally to the collecting ducts. • Glomerular filtration rate (GFR) is the plasma volume filtered by the kidneys per unit of time and is used to assess the kidney function. GFR can be estimated by calculating a patient’s creatinine clearance. Additionally, trends in creatinine clearance can be used to predict perioperative outcomes. ANATOMY

• Gross anatomy of the kidney: – Consists of an outer cortical layer and inner medulla. – Renal artery, renal vein, and ureter enter/exit the kidney at the hilus on the midportion of the concave side. – At the hilus, the ureter dilates into the renal pelvis. The renal pelvis further divides into many tube-like calyces that combine to form the renal parenchyma. – Sympathetic innervation is via the T8-L1 preganglionic fibers. – Parasympathetic input is from the vagus nerve. • Gross anatomy of the ureter: – Muscular tubes propel urine from the renal pelvis to the bladder. – The lumen is lined with transitional epithelium.

– Descends anterior to the psoas muscle and crosses the pelvic brim at the bifurcation of the iliac arteries. – Ureters enter the bladder at the vesicoureteric junction. – Ureterovesical valves prevent backflow of urine. • Gross anatomy of the bladder: – Hollow, muscular, elastic organ that collects urine excreted by the kidney. – The bladder wall is composed of a smooth muscle called detrusor. – Internal surface consists of the transitional epithelium, cuboidal cells that can expand and contract to support volume fluctuations. – Sympathetic innervation is via T11-L2 – Parasympathetic innervation is from S2–S4. Bladder stretching induces the parasympathetic nervous system to contract the detrusor muscle and expel urine to the urethra

PHYSIOLOGY/PATHOPHYSIOLOGY

• Postrenal failure occurs when urine flow from both kidneys is obstructed. This can result from obstruction of a single kidney in the presence of a diseased contralateral kidney or partial or complete obstruction of the bladder or urethra. Specific instances where this can occur are: – Urethral obstruction bilaterally, such as stones or strictures – Bladder obstruction – Neurogenic bladder – Prostatic hypertrophy – Obstruction of the renal pelvis – Blood clots – Cancer of the bladder, prostate, or cervix – Mechanical obstruction of a Foley catheter • Urinary obstruction increases renal intraluminal pressure with resultant: – Decreased renal blood flow – Decreased glomerular filtration rate – Decreased tubular function; distal tubule injury impairs sodium reabsorption with accompanying hyperkalemic renal tubular acidosis – Systemic hypertension via an unknown mechanism, but possibly involving renin– angiotensin activation and volume overload – Pain from distension of the renal capsule, collecting system, or bladder. More common with acute complete obstruction such as ureteral calculus; slow-developing obstructions such as tumors tend to cause less pain – Prolonged obstruction leads to tubular atrophy and irreversible injury

Pediatric Considerations

Anatomic abnormalities are the most common cause of urinary obstruction in children. They include urethral strictures and stenosis of the ureteropelvic or ureterovesical junctions. Geriatric Considerations

The incidence of benign prostate hypertrophy (BPH) increases with age. Eighty percent of

men over the age of 80 years have BPH and therefore are at a higher risk for urinary obstruction and postrenal failure Pregnancy Considerations

• Hydronephrosis and hydroureter without evidence of obstruction is a normal finding present in 80% of pregnancies • More likely to occur on the right side • A dilated collecting system is a risk factor for pyelonephritis

PERIOPERATIVE RELEVANCE

• Patients at increased risk for postrenal dysfunction: – Anticholinergic drugs (acute or chronic): Decreased detrusor contractility places patients at increased risk postoperatively. – Narcotics: Decreased detrusor contractility and ureteral colic. – Benign prostatic hypertrophy: Risk is increased with intraoperative narcotics and missed doses of chronic alpha blockade. – Neuraxial blocks: Blocking the S2–S4 nerve roots can lead to decreased bladder contractility. Advanced age, history of BPH, and neuraxial narcotics can further increase this risk. A urinary catheter should always be used intra-operatively with a neuraxial block. – Preoperative renal impairment: The stress response to surgery can induce a decrease in RBF and GFR, ultimately leading to ischemic damage. This can exacerbate a co-existing postrenal disorder. • Postrenal AKI in the intraoperative period: Usually noticed as a decrease or cessation of urinary output in patients with a bladder catheter. Kinks, clots, or other reversible obstructions should be ruled out prior to presumptively assuming that there is a prerenal or intrarenal cause. It may also present as hypertension or hypervolemia. • Postrenal AKI in the Post Anesthesia Care Unit (PACU) typically presents as an inability to void. Tachycardia, hypertension, and abdominal pain are also common. Bladder ultrasound scan may be considered and can avoid the placement of a catheter. A catheter should be placed if there is evidence of bladder distension on ultrasound. Ability to void is not a criterion for discharge at all institutions (some may use it for urologic or laparoscopic procedures or if neuraxial anesthesia is used). • Postrenal AKI on the floor or ICU: Presents with signs of fluid overload (tachycardia, hypertension, or pulmonary edema in severe cases) as well as decreased or absent urine output. Electrolyte disturbances such as hyperkalemia and metabolic acidosis can be present as well. • Diagnosis – A serum BUN:Cr >15 can result from increased tubular pressure causing BUN reabsorption. However, this is not a marker of acute change. Trends can be monitored to track progression of renal impairment over time. – Fractional excretion of sodium (FENa) may initially be <1% before tubular function is compromised – Renal ultrasound is the test of choice to diagnose urinary tract obstruction. It can assess for hydronephrosis or hydroureter without the risk of radiocontrast. It has a 25% false

positive rate. False negatives may initially occur due to the low compliance of the collecting system (negative for dilation) or in the setting of retroperitoneal fibrosis or tumor surrounding the collecting system (prevents dilation). – CT scans should be considered as a follow up to a positive ultrasound – Intravenous pyelogram (IVP) should be considered if there is a high suspicion for calculi. It has a low false positive rate, can identify the exact level of obstruction, and requires contrast agent. Contrast agents should be used with caution as they can be highly allergenic and may worsen kidney injury. Bicarbonate infusions are often co-administered to reduce the risk of kidney injury. • Management of postrenal AKI: The primary goal of treatment is to re-establish urine output, especially if there is complete obstruction. Definitive treatment is a secondary goal. – Obtain early urologic consult – Insert a urinary catheter if one is not already in place – Temporary treatments are typically reserved for complete obstruction, infection, AKI, transplanted kidney, or pregnancy and are meant to quickly relieve obstruction and prevent deterioration. They include a cystoscopy with retrograde stent placement or percutaneous nephrostomy tubes. Both have a high success and low complication rate. – A meta-analysis that compared retrograde stents to percutaneous nephrostomy tubes did not show one to be superior to the other at relieving obstruction and resolving sepsis (2) [B]. – Antibiotic therapy may be started if the urine is cloudy after the obstruction is relieved. Typically, either a fluoroquinolone or ampicillin/gentamicin is started empirically and titrated to culture results. – Diuresis after the obstruction is relieved can result in a UOP as high as 500–1,000 mL/hr (secondary to overaggressive IV fluid administration causing volume expansion and continued high urine output). Hypovolemia and hypotension may result, requiring fluid administration and monitoring, as appropriate. – Definitive treatment is usually delayed for 2–3 weeks until the acute infection is treated. – Renal recovery after correction of the obstruction is dependent on the severity and duration of obstruction.

EQUATIONS

• Fractional excretion of sodium (FENa) = (Urine sodium / Plasma sodium) / (Urine creatinine / Plasma creatinine) • The RIFLE criteria provide a uniform definition for AKI created by the Acute Dialysis Quality Initiative. It is based on the elevation of SCr and change in urine output and consists of 3 graded levels of injury and 2 outcome measures. – Risk = 1.5 × increase SCr, GFR decrease 25%, Uo <0.5 mL/kg for 6 hours

– Injury = 2 × increase SCr, GFR decrease 50%, Uo <0.5 mL/kg for 12 hours

– Failure = 3 × increase SCr, GFR decrease 75%, Uo <0.5 mL/kg for 24 hours or anuria for 12 hours – Loss = complete loss kidney function requiring dialysis for >4 weeks – ESRD = complete loss of kidney function requiring dialysis for more than 3 months

• As the RIFLE stage increases, mortality increases (3)[A].

REFERENCES

1. Licurse A. Renal Ultrasonography in the evaluation of acute kidney injury. Arch Intern med. 2010;170(21):1900–1907.

2. Ramsey S. Evidence-based drainage of infected hydronephrosis secondary to ureteric calculi. J Endourol. 2010;24(2):185–189. 3. Uchino S. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med. 2006;34:1913–1917.

ADDITIONAL READING

• http://www.asn-online.org/publications/ (American Society of Nephrology)

See Also (Topic, Algorithm, Electronic Media Element) • Cystoscopy • Postrenal acute kidney injury • Ureteral reimplantation • Postoperative renal dysfunction • Glomerular filtration rate

CODES ICD9 • 584.9 Acute kidney failure, unspecified • 599.60 Urinary obstruction, unspecified ICD10 • N13.8 Other obstructive and reflux uropathy • N17.9 Acute kidney failure, unspecified

CLINICAL PEARLS

• Mechanical obstruction of the urinary catheter is a common cause of anuria in the PACU. Early recognition of a kinked catheter can prevent an expensive workup and harm to the patient. • Renal ultrasound is a non-invasive test to evaluate for hydronephrosis. It avoids the use of potentially nephrotoxic contrast in patients who already have AKI. • Careful attention must be paid to a patient’s volume status after reversal of urinary obstruction and subsequent post-obstructive diuresis. • Dosing of renal metabolized or eliminated drugs may have to be adjusted. • Electrolyte disturbances may be present. – Hyponatremia: If due to water excess, UNa >20 mmol/L; if due to excessive sodium

retention, UNa <20 mmol/L.

– Hyperkalemia: May see peaked T-waves, arrhythmias. Chronic hyperkalemia is better tolerated than acute.

POTASSIUM

Suzanne Strom, MD

BASICS DESCRIPTION

• Potassium is necessary for the maintenance of the cellular membrane potential, intracellular osmotic pressure, and transmission of action potentials. • Normal plasma [K+] is 3.5–5 mEq/L; normal intracellular [K+] is 140 mEq/L. A redistribution or shifting of K+ between the ECF and ICF compartments can result in marked changes in their concentration without a change in total body potassium content • Hypokalemia is defined as a plasma [K+] <3.5 mEq/L and can result in arrhythmias, decreased cardiac contractility, myalgias, and respiratory depression. • Hyperkalemia is defined as a plasma [K+] >5.5 mEq/L and can result in weakness and arrhythmias that can progress to cardiac arrest.

PHYSIOLOGY PRINCIPLES

• Intracellular K+ comprises 98% of total body stores; whereas intravascular and extracellular compartments comprise 2%. This discrepancy is the result of maintaining the cell membrane’s resting potential. • The membrane resting potential is an electrochemical gradient that plays a role in transport, signal transduction, myocardial pacemakers and contractility, and cell volume homeostasis. – The Na+–K+ ATPase enzyme pump (embedded in the cell membrane) exchanges 3 Na+ ions extracellularly for 2 K+ ions intracellularly while consuming one ATP molecule. In doing so, it maintains the electrochemical gradient with an intracellular [K+] of 150 mEq/L, compared to an intravascular concentration of approximately 3.5–5 mEq/L. • Additional mechanisms: K+ concentrations between the two compartments are also affected by pH, insulin, and catecholamines or sympathomimetics with beta-adrenergic receptor activity. – pH: The Na+–H+ ion exchanger allows for the cells to function as a buffer against alkalemia or acidemia. In alkalemia, H+ ions move extracellularly to offset the disturbance; Na+ moves intracellularly. This increase in intracellular Na+ stimulates the Na+–K+ ATPase; thus the buffering effect results in a secondary intracellular shifting of K+. Conversely, in acidemia, H+ ions move intracellularly in exchange for extracellular Na+ movement; this process reduces intracellular shifting of K+ via the Na+–K+ ATPase. – Insulin: Activates the Na+–K+ ATPase in cells. – Beta-adrenergics: Activates adenylyl cyclase and increases cAMP levels, which, in turn, activates protein kinase A. This results in the activation of calcium-gated K+ channels as well as Na+–K+ ATPase with resultant intracellular shifting of potassium. • K+ excretion: In addition to intracellular shifting, K+ levels are also regulated by the

kidneys (90%), the gastrointestinal tract, and sweat. Aldosterone, a mineralocorticoid, lowers the plasma K+ concentration at several levels in the renal tubule.

ANATOMY

Depolarizing cells (with potassium repolarization) • Pacemaker cells spontaneously depolarize (sodium enters the cell and makes the resting potential positive). Depolarization serves as an electrical signal that passes to adjacent conduction and myocardial cells in a domino-like fashion. Repolarization of pacemaker cells is primarily via potassium efflux (Phase 3). • Myocardial cell depolarization is coupled to mechanical contraction and blood being “pumped.” Repolarization is mediated via potassium efflux; however, it is divided into an early (phase 1) and late (phase 3) phase by an extended plateau. • Nerve cells communicate and transmit their signal via electrical signaling that involves changes in resting membrane potential. Repolarization occurs via potassium efflux. PHYSIOLOGY/PATHOPHYSIOLOGY

• Acute [K+] changes are less well-tolerated than chronic changes. • Hypokalemia is the result of either reduced total body stores, or redistribution into the intracellular space. – Reduced total body K+ stores may result from reduced intake or increased excretion (renal or extra-renal). Reduced intake: The minimum daily requirement is 40–50 mEq/day Increased renal excretion: Type I and II renal tubular acidosis, diabetic ketoacidosis, diuretic therapy, carbonic anhydrase inhibitors, ureterosigmoidostomy, posthypercapnia, increased mineralocorticoid activity (aldosterone), and hemodialysis. Increased extra-renal excretion: Diarrhea, vomiting and nasogastric suction, increased sweat loss, and laxative abuse. – Intracellular shifting can occur perioperatively via alkalemia, exogenous insulin administration, and beta-adrenergics. Alkalemia can be metabolic and result from excessive bicarbonate administration or hyperventilation (mechanical ventilation, pain, stimulation). Exogenous insulin may be administered for glucose control. Hyperalimentation may increase endogenous insulin release. Beta-adrenergic excess may be exogenous (administration of epinephrine, dobutamine, isoproteronol, ephedrine; nebulizer/inhaler) or endogenous (thyrotoxicosis). • Clinical manifestations of hypokalemia result from hyperpolarization of the cell membrane. In cardiac pacemaker cells, it also increases the duration of repolarization. – Cardiac: Dysrhythmias (premature atrial contractions, premature ventricular contractions, AV block, ventricular tachycardia, ventricular fibrillation), conduction defects (increased PR and QT intervals, reduced T wave amplitude, T wave inversion or U waves, and ST segment depression), and potentiation of digitalis toxicity. – Skeletal muscle: Weakness, paralysis, rhabdomyolysis, fasciculations and tetany (typically do not manifest until the serum [K+] <3 mEq/L). – Gastrointestinal: Ileus, constipation.

– Renal: Nephrogenic diabetes insipidus, impaired urinary concentrating abilities, increased NH3 production, and hypokalemic nephropathy.

• Hyperkalemia is the result of either increased total body stores or redistribution out of the intracellular compartment into the serum. – Increased total body K+ stores may result from increased intake or decreased excretion (renal or extra-renal). Increased intake: Transfusions, intake of sodium substitutes, potassium penicillin, or increased absorption from a ureterojejunostomy. Decreased renal excretion: Marked reductions in glomerular filtration, decreased mineralocorticoid (aldosterone) activity, or a defect in potassium secretion in the distal nephron (distal RTA). – Extracellular shifting can occur perioperatively with succinylcholine administration, acidemia, hemolysis, rhabdomyolysis, massive tissue trauma, hyperosmolality, digitalis overdoses, and beta-adrenergic blockade. It can also occur with cell lysis following chemotherapy, administration of arginine hydrochloride, and during episodes of hyperkalemic periodic paralysis. Succinylcholine: Plasma [K+] can increase 0.5–1 mEq/L with administration of an intubation dose. Acidemia: Hypoventilation results in hypercarbia and can be caused perioperatively by respiratory depression from inhalational anesthetics, benzodiazepines, and opioids. Cell destruction: K+ release may occur with trauma, burns, rhabdomyolysis, hemolysis, tumor lysis, or reperfusion of an ischemic limb or organ. Beta-adrenergic blockade: Increased potassium may be seen in patients receiving betaadrenergic blockade Insulin deficiency • Clinical manifestations of hyperkalemia result from hypopolarization of the cell membrane. In cardiac pacemaker cells, it also decreases the duration or repolarization. – Cardiac: Dysrhythmias leading to CV collapse. Peaked T waves (6–7 mEq/L), ST depression, prolonged P–R interval and widened QRS (10–12 mEq/L), ventricular fibrillation or asystole. – Skeletal muscle: Weakness, paralysis. – Gastrointestinal: Ileus, constipation. – Renal: Metabolic acidosis by interfering with renal ammonium (NH4+) excretion. • Potassium artifact might be seen with hemolysis of blood sample from venipuncture.

PERIOPERATIVE RELEVANCE

• Hypokalemia: [K+] values of 2.0–2.5 mEq/L are likely to cause arrhythmias and muscular weakness; furthermore, it can potentiate the effects of neuromuscular blocking agents and can delay recovery. – Potassium replacement: Oral and intravenous preparations are available. Perioperative correction often involves intravenous KCl preparations. The maximum recommended rate of infusion via a peripheral IV is 10 mEq/hr and via a central line is 20 mEq/hr. Higher rates of administration carry the risk of hyperkalemia or arrhythmias.

– Urgent or emergent surgery may be performed with careful EKG monitoring and avoidance of hyperventilation, alkalosis, and beta-adrenergics. Potassium and magnesium replacement should be concurrently performed. • Hyperkalemia – Urgent or emergent surgery may be performed with careful EKG monitoring and avoidance of hypoventilation or acidosis. – Treatment involves: Membrane stabilization. Calcium gluconate 10% (70 kg patient): 10–30 mL IV over 10– 20 minutes. Intracellular shift (for a 70 kg patient): Glucose 25–50 g IV (avoid hypoglycemia) with regular insulin 10–20 units IV. Sodium bicarbonate: 50–100 mEq IV. Hyperventilation: With each pH change of 0.1, there is an inverse change in [K+] of 0.5 mEq/L (goal: PaCO2 = 25–30 mm Hg). Removal: Diuretics, exchange resins (Kayexalate), dialysis.

REFERENCES

1. Katerinis I, Fumeaux Z. Hypokalemia: Diagnosis and treatment. Rev Med Suisse. 2007;3(101):579–582. 2. Parham Q, Mehdirad A, Biermann K, et al. Hyperkalemia revisited. Tex Heart Inst J. 2006;33(1):40–47.

ADDITIONAL READING

• Lin SH, Halperin ML. Hypokalemia: A practical approach to diagnosis and its genetic basis. Curr Med Chem. 2007;14(14):1551–1565.

See Also (Topic, Algorithm, Electronic Media Element) • Buffering systems • Cardiac action potential • QT prolongation • Hyperkalemia • Hypokalemia

CLINICAL PEARLS • Disturbances with either total body or plasma K+ concentrations can cause weakness and possibly lethal arrhythmias. Careful preoperative and intraoperative monitoring of both K+ levels and factors that affect intracellular shifting is crucial. • Anaesthetists must determine whether to delay surgery in order to optimize plasma potassium levels or proceed.

PREECLAMPSIA

Henry Ra, MD Judith A. Turner, MD, PhD

BASICS DESCRIPTION

• Preeclampsia is a pregnancy-specific, multi-organ system disease characterized by hypertension and proteinuria beginning after 20 weeks gestation and resolving by 6–12 weeks postpartum. • May be mild, severe, or part of a larger spectrum of diseases, including pregnancy-induced hypertension, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. EPIDEMIOLOGY Prevalence

5–8% of all pregnancies; rising incidence in the US. Morbidity

• Maternal morbidity: Seizures (eclampsia), HELLP syndrome, renal disease, pulmonary edema, hemorrhage, disseminated intravascular coagulation (DIC), cerebrovascular accident. • Fetal morbidity: Placental abruption, fetal growth restriction, preterm delivery. • Increased incidence of Cesarean section in severe cases. • Early onset preeclampsia (before 34 weeks gestation) associated with increased risk for future cardiovascular disease. Mortality

• Comprises ∼10–15% of maternal death worldwide. • Third leading cause of maternal mortality in the US (behind pulmonary embolus and hemorrhage). • Late onset preeclampsia (after 34 weeks gestation) has lower maternal and fetal morbidity and mortality compared to early disease. ETIOLOGY/RISK FACTORS

• Maternal factors: – Nulliparity – Preeclampsia in previous pregnancy – Family history of preeclampsia – Pre-gestational diagnosis of chronic hypertension, diabetes, vascular, or renal disease – Obesity (BMI >35) – Presence of antiphospholipid antibodies

– African American or Filipino race – Age >40 years • Paternal factors: Male who previously fathered a preeclamptic pregnancy; male born from a preeclamptic pregnancy.

PHYSIOLOGY/PATHOPHYSIOLOGY Two proposed hypotheses:

• An atypical maternal immune response to embryonic trophoblasts results in impaired invasion of trophoblastic cells into the uterine wall. This leads to maladaptation of myometrial spiral arteries with reduced, high-resistance, utero-placental flow. The irregular placental perfusion can cause placental hypoxia and the release of inflammatory cytokines into the maternal circulation with consequent endothelial dysfunction. • An imbalance of placental production of prostacyclin and thromboxane can result in systemic vasoconstriction and placental ischemia.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess the severity of disease and end-organ damage. • Avoid hemodynamic extremes, especially when general anesthesia is attempted (intubation and extubation). • Gentle fluid resuscitation with caution of excess fluid administration. • Delivery of fetus/placenta is the only cure.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Seizures, visual disturbances, headaches • Pulmonary and peripheral edema • Shortness of breath • Abdominal pain • Nausea/vomiting • Vaginal bleeding • Decreased urine output

History

• Prenatal history and care, including pre-gestational diagnoses of hypertension and renal disease. • Fetal anomalies/intrauterine growth restriction (IUGR). • Family history • History of preeclampsia with previous pregnancy • Reduced fetal movement

Signs/Physical Exam • Hypertension • Proteinuria

• Hypovolemia – ∼10% fluid deficit in mild preeclampsia – ∼35% fluid deficit in severe preeclampsia • Pharyngolaryngeal edema • Tachypnea, crackles at lung bases • Right upper quadrant pain • IUGR

MEDICATIONS

• Prevention: Aspirin may be prescribed for high-risk patients (abnormal uterine artery Doppler at 16 weeks gestation). It is not recommended for prophylactic use in low-risk patients. • Antihypertensives – Hydralazine (first line): 5–10 mg IV q15 minutes – Labetalol (first line): 20 mg IV q10 minutes up to a maximum dose of 300 mg. – Nifedipine (second line): 10 mg PO TID titrated to effect for maximum dose of 120 mg daily. Should be avoided in women with CAD, DM >15 years, or >45 years old. – Continuous epidural infusion can block sympathetic nerve fibers and may assist with BP control. • Magnesium sulfate (first line): 4–6 g IV bolus over 15 minutes, followed by 1–2 g/hr for seizure, prophylaxis. Therapeutic level ∼6–8 mEq/mL • Ergot alkaloids (e.g., Methergine) should be avoided as it may cause a hypertensive crisis.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• 24-hour urine protein • Urine protein: urine creatinine ratio • Hgb/Hct/platelet count • Liver enzymes to assess for HELLP syndrome • Blood type and screen or cross-matching, as appropriate • Fetal ultrasound • Echocardiogram if suspicion for cardiomyopathy

CONCOMITANT ORGAN DYSFUNCTION

• CNS: Visual disturbance, headache, eclamptic seizures, or cortical blindness may be due to cerebral edema. • CV: Vasoconstriction due to endothelial dysfunction and consequent hypertension. • Respiratory: Increased risk of pulmonary edema due to lower colloid oncotic pressures and increased capillary permeability • Renal: Proteinuria due to increased permeability of albumin and other plasma proteins. • Hematologic: Microconsumption coagulopathy, and/or thrombocytopenia. • GI: Hepatic edema causing RUQ pain; rupture of Glisson’s capsule in severe disease may lead to hepatic hemorrhage; elevated liver enzymes in HELLP syndrome. CIRCUMSTANCES TO DELAY/CONDITIONS

• Appropriate BP control is necessary before induction of general anesthesia, even in emergent cases. • Coagulopathy may preclude the use of neuraxial anesthesia.

CLASSIFICATIONS

• Mild preeclampsia: Systolic >140 mm Hg or diastolic >90 mm Hg with proteinuria (>300 mg/24 hrs) • Severe preeclampsia: Systolic >160 mm Hg or diastolic >110 mm Hg and/or end-organ damage. – Renal involvement defined as proteinuria >3 g/24 hrs, 3+ on urine dipstick, or sudden oliguria – CNS involvement – Pulmonary edema – Liver dysfunction – RUQ/epigastric pain – Thrombocytopenia – HELLP syndrome – Evidence of fetal compromise • Eclampsia: New onset of grand mal seizures occurring during or after pregnancy that do not have another identifiable cause.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Avoid benzodiazepines and limit narcotics. • Nonparticulate antacid (i.e., bicitrate) • MgSO4 infusion for seizure prophylaxis Special Concerns for Informed Consent

• Regional anesthesia and coagulopathy • Possible need for blood transfusion • Possible need for invasive monitoring

INTRAOPERATIVE CARE Choice of Anesthesia

• ACOG and ASA recommend regional anesthesia in patients without evidence of coagulopathy. • Early placement of epidural should be considered to avoid general anesthesia. • Spinal anesthesia is a suitable alternative to epidural for Cesarean section even in severe preeclampsia. Monitors

• Standard ASA monitors • Consider arterial line for better hemodynamic monitoring. • CVP and PAP monitoring is rarely necessary.

Induction/Airway Management

• Neuraxial techniques: Consider supplemental O2 via facemask or nasal canula for patients

with neuraxial anesthesia/analgesia. • General endotracheal anesthesia (GETA) – Rapid sequence induction, along with aspiration precautions. – Difficult airway: There is an increased risk of failed intubation due to pharyngolaryngeal edema. Be prepared for a difficult airway, including having a supraglottic device available. – Careful attention to BP management with induction and intubation; intracranial hemorrhage, secondary to severe hypertension, is the leading cause of morbidity and mortality in preeclamptic women. Consider having esmolol and nitroglycerin available. – Hypotension with induction may lead to fetal compromise/distress. Maintenance

• Neuraxial. In the OR, intermittent boluses with high concentration local anesthetics (possibly without epinephrine) for surgical anesthesia/analgesia. • GETA. Less than 0.5 MAC of volatile anesthetic supplemented by nitrous oxide after delivery of the fetus. All inhalational agents cause uterine relaxation and can contribute to postpartum hemorrhage. – MgSO4 causes prolonged duration of non-depolarizing neuromuscular blockade. • Gentle fluid resuscitation with caution to avoid fluid overload

Extubation/Emergence

• The patient is considered to have a full stomach. • Avoid severe hypertension.

FOLLOW-UP BED ACUITY

• ICU admission may be indicated if there is evidence of severe end-organ damage, including renal failure, cerebral hemorrhage, hepatic rupture, and/or pulmonary edema. • Routine postpartum ward may be appropriate in a patients without pulmonary edema or hemodynamic derangements. • Preeclampsia and all of its associated complications may present de novo after delivery. • IV MgSO4 should continue for 24 hours postpartum. COMPLICATIONS

• HELLP, DIC, eclampsia, pulmonary edema, cerebral hemorrhage, placental abruption. • MgSO4

– Toxicity: Decreased deep tendon reflexes, EKG changes, respiratory depression (10–15 mEq/L), cardiac arrest (25 mEq/L) – Fetal depression

REFERENCES

1. Turner JA. Diagnosis and management of pre-eclampsia: An update. Int J Womens Health. 2010;2:327–337. 2. Steegers EA, von Dadelszen P, Duvekot JJ, et al. Lancet. 2010;376(9741):631–644. 3. Gogarten W. Preeclampsia and anaesthesia. Curr Opin Anaesthesiol. 2009;22:347–351.

4. American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Practice Guidelines for Obstetric Anesthesia. Anesthesiology. 2007;106:843–863. 5. Visalyaputra S, Rodanant O, Somboonviboonvv W, et al. Spinal versus epidural anesthesia for cesarean delivery in severe preeclampsia: A prospective randomized, multicenter study. Anesth Analg. 2005;101:862–868.

ADDITIONAL READING

• American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin: Diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol. 2002;99 (1):159–167. • Lewis G , ed. 2007. The confidential enquiry into maternal and child health (CEMACH). Saving mothers’ lives: Reviewing maternal deaths to make motherhood safer-2003–2005. 6. The Seventh Report on Confidential Enquiries into Maternal Deaths in the United Kingdom. London: CEMACH. • www.preeclampsia.org

See Also (Topic, Algorithm, Electronic Media Element) • HELLP syndrome • Pregnancy-induced hypertension • Eclampsia

CODES ICD9 • 642.40 Mild or unspecified pre-eclampsia, unspecified as to episode of care or not applicable • 642.50 Severe pre-eclampsia, unspecified as to episode of care or not applicable ICD10 • O14.00 Mild to moderate pre-eclampsia, unspecified trimester • O14.10 Severe pre-eclampsia, unspecified trimester • O14.90 Unspecified pre-eclampsia, unspecified trimester

CLINICAL PEARLS

• Preeclampsia is a relatively common, transient multi-organ system disease diagnosed after 20 weeks gestation. • Early placement of a epidural should be considered to assist with BP control and as a preferred alternative to general anesthesia. Rule out coagulopathy and thrombocytopenia before neuraxial anesthesia is attempted. • When a GETA is indicated, be prepared for a difficult tracheal intubation and have back-up airway equipment, including supraglottic devices, if available.

PREGNANCY INDUCED HYPERTENSION Richard C. Jensen, MD Judith A. Turner, MD, PhD

BASICS DESCRIPTION

• Pregnancy-induced hypertension (PIH) is a spectrum of hypertensive disorders of pregnancy including gestational hypertension (GH), chronic hypertension, preeclampsia, and eclampsia. • GH is defined as systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg in a woman without preexisting hypertension or signs of preeclampsia. It manifests after 20 weeks gestation and resolves by 12 weeks postpartum. • Chronic hypertension involves either pre-pregnancy hypertension (SBP >140 mm Hg or DBP >90 mm Hg) or failure of hypertension to resolve within 12 weeks postpartum. • Preeclampsia is the onset of hypertension and proteinuria after 20 weeks gestation with remission by 6–12 weeks postpartum. Eclampsia is new onset of seizures or unexplained coma in a woman with signs and symptoms of preeclampsia. EPIDEMIOLOGY Prevalence

• Hypertension complicates ∼20% of pregnancies • GH is encountered in ∼5% of pregnancies. • Chronic hypertension is present in 1–2% of pregnancies. • Preeclampsia–eclampsia develops in ∼5% of pregnancies in the US; nearly 20% of women with chronic hypertension develop preeclampsia. Morbidity

• Sustained hypertension can result in end-organ damage such as renal failure, left ventricular hypertrophy, and/or cerebrovascular accident. • Maternal morbidity associated with preeclampsia–eclampsia includes pulmonary edema, disseminated intravascular coagulation, hepatic rupture, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), and seizures. • Fetal morbidity is due to increased incidence of placental abruption, intrauterine growth restriction, and preterm delivery. Mortality

• PIH is the third leading cause of maternal mortality in the US behind pulmonary embolus and hemorrhage. It accounts for ∼10% of all deaths, with intracranial hemorrhage as the primary cause. • Approximately 10% of neonatal deaths occur in the presence of PIH.

ETIOLOGY/RISK FACTORS

• GH risk factors: History of GH in a previous pregnancy. • Chronic hypertension risk factors – Essential chronic hypertension: Obesity, African American ethnicity, increased salt intake, hyperlipidemia, family history – Secondary chronic hypertension: Oral contraceptive use, renal disease, aortic coarctation, endocrine disorders • Preeclampsia-eclampsia risk factors – Maternal: Age >40 years, African American ethnicity, obesity, hypertension, diabetes, thrombotic vascular disease (interestingly, smoking decreases the risk) – Pregnancy-associated: Nulliparity, multiple gestations, molar pregnancy – Fetal: Gestational age <28 weeks – Paternal: History of fathering a preeclamptic pregnancy with another woman

PHYSIOLOGY/PATHOPHYSIOLOGY

• Chronic hypertension: Adrenergic hyperactivity and altered calcium homeostasis leading to decreased peripheral vascular resistance and cardiac stimulation; increased vasoreactivity leading to elevated systemic vascular resistance; increased renal reabsorption of salt and water leading to increased circulating blood volume. • The cause of preeclampsia remains unclear.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Control hypertension (target SBP <140 mm Hg; DBP <90 mm Hg). • Assess the severity of disease and end-organ damage. • Evaluate for preeclampsia and implement seizure prophylaxis if severe. • Accelerate fetal lung maturity for gestational age <36 weeks with betamethasone if preterm delivery is anticipated. • Regional anesthesia is preferred in the absence of coagulopathy and/or thrombocytopenia. Neuraxial analgesia may facilitate management of hypertension and avoidance of general endotracheal anesthesia for an emergent procedure. • Prepare for urgent delivery if indicated. Indications for emergent delivery include nonreassuring fetal heart tones lasting >10 minutes, placental abruption, end-organ damage, and/or seizure.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Decreased fetal movement • Preeclampsia: Shortness of breath, abdominal pain, seizures, visual disturbances, headaches

History

• Prenatal history: Nulliparity, multiple gestations, molar pregnancy • PIH risk factors • Fetal anomalies/intrauterine growth restriction • Fasting status if urgent/emergent Cesarean delivery becomes necessary.

Signs/Physical Exam

• Airway: Pharyngolaryngeal edema • Pulmonary: Pulmonary edema, hypoxemia. • Cardiovascular: Hypertension, LV hypertrophy, and/or decreased CVP. • Hematologic: Anemia, thrombocytopenia, and/or disseminated intravascular coagulation (DIC). • Renal: Decreased GFR, increased proteinuria, increased uric acid, increased urine protein:creatinine ratio, and/or oliguria. • Hepatic: Increased serum transaminases, hepatic edema, hepatic hematoma, periportal hepatic necrosis, rupture of Glisson’s capsule with hepatic hemorrhage • Neurologic: Cerebral edema, cerebral hemorrhage. • Placental: Intrauterine growth restriction, non-reassuring fetal heart tracing, and/or placental abruption. MEDICATIONS

• GH or chronic hypertension: Methyldopa 250 mg PO BID, maximum dose 3g/day; Labetalol 100 mg PO BID or TID, maximum dose 1,200 mg/day; Nifedipine 30–90 mg PO/day, maximum dose 120 mg/day. • Preeclampsia–eclampsia. antihypertensives: Hydralazine 5–10 mg IV q15 minutes; Labetalol 20 mg IV every 10 minutes, maximum dose of 300 mg. Seizure prophylaxis: Magnesium sulfate 4–6 g IV bolus over 15 minutes, followed by 1–2 g/hr. • Ergot alkaloids (e.g., Methergine) should be avoided due to risk of causing hypertensive crisis. • Betamethasone to stimulate fetal lung maturity in the setting of preterm delivery.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Labs: Urinalysis for proteinuria, CBC (especially platelets and Hct), CMP (magnesium), coagulation studies, type and cross. • Imaging studies (if indicated): Chest x-ray (pulmonary edema), head CT (useful in identifying cerebral edema, loss of cortical sulci, and/or cerebral hemorrhage), abdominal ultrasound, CT, or MRI (if hepatic infarction, hematoma or rupture suspected), echocardiogram (if cardiac dysfunction is suspected). CIRCUMSTANCES TO DELAY/CONDITIONS

• In cases of severe PIH prior to fetal lung maturity (24–34 weeks gestational age), consider delaying delivery for 48 hours after the administration of systemic steroids. • BP control is necessary prior to induction of general anesthesia, even in emergent deliveries.

CLASSIFICATIONS

• GH: Elevated BPs after 20 weeks gestation that resolves by 12 weeks postpartum. • Chronic hypertension: Pregnancy hypertension or hypertension in pregnancy that fails to resolve following delivery. • Preeclampsia–eclampsia: The new onset of hypertension and proteinuria after 20 weeks

gestation. • Chronic hypertension with superimposed preeclampsia: The development of preeclampsia in a parturient with chronic hypertension.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Aspiration prophylaxis in the setting of GETA (nonparticulate antacids, metoclopramide, H2 blockers) • BP control • Seizure prophylaxis for preeclampsia–eclampsia.

Special Concerns for Informed Consent

• Regional anesthesia and coagulopathy. • Blood products in the setting of thrombocytopenia, coagulopathy, and/or hemorrhage. • Possible need for invasive monitoring if severe, refractory hypertension and/or evidence of end-organ damage. INTRAOPERATIVE CARE Choice of Anesthesia

• Neuraxial anesthesia (spinal or epidural) preferred. Contraindications for neuraxial anesthesia include patient refusal, elevated intracranial pressure (ICP), inability to cooperate, evidence of coagulopathy, signs of local infection. • General anesthesia may be necessary in emergent deliveries (fetal distress, placental abruption, hepatic rupture, severe pulmonary edema, seizure, and/or end-organ dysfunction). – Associated with increased risk of aspiration, transient neonatal depression, severe hypertension, and cerebral hemorrhage. – Maternal mortality is 7-fold greater with GETA compared with neuraxial anesthesia. Failed intubations are 10 times more likely in obstetric patients compared with general population.

Monitors

• Pulse oximetry: Decrease in SpO2 in the setting of pulmonary edema, respiratory depression, and/or pulmonary aspiration. • BP monitoring: Consider invasive BP monitoring in the setting of refractory hypertension (BP >180/120) or for frequent blood sampling. • Central venous pressure: May be useful in determining volume status and for infusion of vasodilators. • Pulmonary arterial catheter rarely indicated but may be useful in the setting of severe cardiac disease and/or pulmonary hypertension. • Urinary output: Useful in evaluation of volume resuscitation and renal function.

• Fetal heart tracing

Induction/Airway Management

• Limit use of benzodiazepines and opioids prior to delivery; use is associated with neonatal depression. • General anesthesia for emergent deliveries. – Rapid sequence intubation with cricoid pressure to minimized risk of aspiration. – Avoid hypertensive response to laryngoscopy with deepening of anesthetic, remifentanil, and/or esmolol.

Maintenance

General anesthesia may be maintained with a combination of volatile anesthetic and nitrous oxide. Volatile anesthetic at <0.5 MAC minimizes a decrease in the uterine tone. IV opioids and benzodiazepines can be given following clamping of the cord. Magnesium sulfate prolongs duration of non-depolarizing neuromuscular blockade. Extubation/Emergence

• Airway edema may necessitate reintubation. • Severe hypertension and cerebral hemorrhage may accompany emergence and extubation.

FOLLOW-UP BED ACUITY

• Hemodynamically stable patients may be monitored on regular postpartum wards. • Magnesium sulfate should be continued for 24 hours postpartum in patients with preeclampsia/eclampsia. Preeclampsia and its associated complications may present de novo after delivery. • ICU admission may be indicated if there is evidence of severe end-organ damage including renal failure, cerebral hemorrhage, hepatic rupture, and/or pulmonary edema.

MEDICATIONS/LAB STUDIES/CONSULTS

• Continue antihypertensive therapy until the BP normalizes. • Follow platelets, INR/PT, hepatic enzymes, BUN/Cr until values normalize. • In the setting of eclampsia, continue seizure prophylaxis for 24 hours following last seizure.

COMPLICATIONS

• GH and chronic hypertension: Development of preeclampsia–eclampsia, hemorrhagic stroke, placental abruption • Complications associated with magnesium sulfate for seizure prophylaxis: Maternal toxicity, uterine atony, postpartum hemorrhage, fetal depression

REFERENCES

1. urner JA.Diagnosis and management of preeclampsia, an update. Int J Womens Health. 2010;2:327–337.

2. American College of Obstetricians and Gynecologists (ACOG) Practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Obstet Gynecol. 2002;99(1):159–167. 3. Practice guidelines for obstetric anesthesia: An updated report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia. Available at: http://www.asahq.org/publicationsAndServices/OBguide.pdf. Accessed on Jan 08, 2011.

ADDITIONAL READING • www.preeclampsia.org

See Also (Topic, Algorithm, Electronic Media Element) • HELLP Syndrome • Preeclampsia • Eclampsia • Hypertension

CODES ICD9 642.90 Unspecified hypertension complicating pregnancy, childbirth, or the puerperium, unspecified as to episode of care or not applicable ICD10 • O13.1 Gestational htn w/o significant proteinuria, first trimester • O13.2 Gestatnl htn w/o significant proteinuria, second trimester • O13.9 Gestational htn w/o significant proteinuria, unsp trimester

CLINICAL PEARLS

• PIH describes a spectrum of diseases: Gestational hypertension, preeclampsia, and chronic hypertension (with or without superimposed preeclampsia). • Preeclampsia is characterized as hypertension and proteinuria diagnosed after 20 weeks gestation. Management involves aggressive BP control, seizure prophylaxis, and monitoring for end-organ damage. Delivery of the fetus and placenta is the only definitive treatment • Regional anesthesia is preferred over general anesthesia for Cesarean delivery. When GETA is necessary, anticipate and treat BP lability and be prepared for a difficult airway.

PRELOAD

Larry C. Field, MD Daniel M. Rusu, MD

BASICS DESCRIPTION

• Unless otherwise specified, preload describes the volume of blood distending the left ventricle at the end of diastole (i.e., end of the ventricular filling phase), also known as left ventricular end-diastolic volume (LVEDV). The concept of preload can also be applied to any chamber of the heart • Direct assessment of cardiac preload requires measurement of the blood volume within the reference chamber. This is generally done via echocardiography which can be performed intraoperatively but is also possible by MRI, CT, radionuclide angiography, and cardiac catheterization. In the perioperative period, preload is often assessed indirectly via interpretation of static cardiac filling pressures and/or the dynamic relationship of filling pressures on cardiac output. PHYSIOLOGY PRINCIPLES

• Static measures of preload: Cardiac preload is a major determinant of cardiac performance via the Frank–Starling mechanism. The curvilinear Frank–Starling curve demonstrates the effect of preload versus contractility (as measured by stroke volume). Until the chamber is grossly overdistended, increasing preload [end-diastolic volume (EDV)] will increase the intrinsic strength of the systolic contraction and increase the stroke volume.

FIGURE 1. Frank—Starling curve: http://www.ncbi.nlm.nih.gov/books/NBK2220/

FIGURE 2. Stroke volume preload dependence

• Ventricular preload (filling volume) is increased by: Increased filling pressure (increased total blood volume, decreased venous compliance, or gravity/Trendelenburg position) or increased myocardial compliance. Chamber compliance determines how much the EDV increases relative to the increased pressure. • Ventricular preload is decreased by: Hypovolemia (dehydration, hemorrhage), impaired atrial contraction (loss of ‘atrial kick’), increased heart rate (decreased filling time), decreased afterload (smaller residual end-systolic volume), and diastolic heart failure (impaired relaxation/compliance). • Although pressure measurements are commonly used as surrogate measures of preload (EDV), it is important to note that the pressure–volume relationship is not linear and is often dynamic. – In the absence of significant lung disease or mitral valve disease, pulmonary artery occlusion pressure (PAOP) approximates LVEDP; LVEDP is assumed LVEDV – In the absence of tricuspid valve pathology, central venous pressure (CVP) or right atrial pressure (RAP) approximates right ventricular end-diastolic pressure (RVEDP); RVEDP is assumed RVEDV – In the absence of significant right heart pathology, pulmonary disease, or mitral valve disease, adequate RVEDV (as suggested by its CVP surrogate) is also assumed to translate into adequate LVEDV (preload for the systemic circulation). – Surrogate pressure measurements may not begin to increase from near zero (slope of pressure–volume relationship is near zero) until ventricular volumes are above 40–50 mL. A curvilinear increase in filling pressure per unit preload volume is then seen until ventricular volumes near their end-diastolic capacity, where the pressure–volume slope increases (this slope assumes a more linear relationship if the pericardium is removed).

FIGURE 3. Pressure-volume relationship of the left ventricle. http://www.cvphysiology.com

• Dynamic measures of preload: Trends indicating the change in stroke volume or blood pressure over different preload conditions are more useful indicators of ongoing volume responsiveness than static pressure surrogates. – When total blood volume is low compared to vascular capacitance (relative hypovolemia with low preload), an adequate fluid challenge (>10 mL/kg of crystalloid given in <30 min) may provide only a transient increase in blood pressure and little (<3 cm H2O) sustained increase in CVP/PAOP – When total blood volume is approaching vascular capacity and cardiac preload is still low, an adequate fluid challenge should provide a sustained blood pressure increase and a sustained (>3 cm H2O) increase in CVP/PAOP.

– When total blood volume is in excess and cardiac preload reserve has been exhausted, ongoing fluid challenges will not further increase blood pressure/cardiac output, but significant sustained CVP/POAP increases will still be seen. – Passive leg raises or Trendelenburg positioning may provide the patient with a significant enough “volume challenge” to determine volume responsiveness. • Under the conditions of regular controlled positive pressure ventilation (>8 mL/kg tidal volumes) and regular sinus heart rhythm, heart–lung interactions will cause cardiac preload conditions to change throughout the respiratory cycle. – Increased systolic pressure, pulse pressure, and stroke volume variations indicate increased cardiac preload dependence and can predict ongoing fluid responsiveness. Depending on the non-invasive cardiac output measuring device and variable selected, a variation of >11–13% of stroke volume often predicts volume responsiveness (1)[A]. Respiratory variation of the pulse oximetry plethysmograph of >14% may also suggest volume responsiveness (2)[B]. Aortic blood flow velocity variation >12% (measured by echocardiography or esophageal Doppler) is similarly highly predictive of volume responsiveness (3)[B]. – Looking at the venous system via bedside ultrasound, an inferior vena cava (IVC) distensibility index >12% predicts volume responsiveness (4)[B]. IVC engorgement occurs as positive pressure ventilation inhibits blood return to the right heart. • In spontaneously ventilating patients, IVC collapse of >50% suggests a CVP <10 and

predicts volume responsiveness.

ANATOMY

• Microscopically, preload describes the sarcomere length related to myocyte stretching. • Macroscopically, preload is the three-dimensional volume of blood within the chamber that is responsible for the one-dimensional sarcomere length of the stretched myocytes.

Pregnancy Considerations

• To avoid IVC compression by the uterus, left uterine displacement (rotation of hips/torso towards left side) is suggested when a parturient (of >24 weeks gestation) would otherwise be positioned supine. • Uterine compression of the IVC may impair venous return and decrease preload, resulting in up to a 30% reduction of cardiac output.

DISEASE/PATHOPHYSIOLOGY

• Volume overload. Upon gross overdistention of the chamber, microscopic myofibrils (myosin and actin) are stretched beyond their ability to optimally overlap, decreasing their strength/contractility and heart failure ensues (Figure 1). • Diastolic dysfunction results in increased filling pressures as a compensatory mechanism to maintain adequate/minimal EDV. Such compensated patients often appear more sensitive to filling pressure/volume decreases and are relatively “preload dependent.” • Myocardial ischemia. Filling of a cardiac chamber during diastole involves both the active (early) relaxation by the myocytes and the passive compliance of chamber’s wall. Active relaxation of a cardiac chamber is decreased during myocardial ischemia. Relaxation (diastolic) abnormalities occur in the ischemic tissue before contraction (systolic) dysfunction is seen. Impaired active relaxation (during ischemia) will result in reduced ventricular filling during diastole, contributing to the appearance of decreased compliance (decreased ventricular volume for same filling pressure). • Left ventricular hypertrophy (LVH). As the ventricular wall thickens, it becomes less compliant. LVH can develop with: – Increased afterload: Hypertension, morbid obesity, and aortic stenosis that result in a chronic increase in work. – Reduced compliance: Infiltrative diseases such as amyloidosis or cardiac tumors where there is an increase in myocardial stiffness. • Rhythm disturbances (tachycardia, heart block, atrial fibrillation, or atrial flutter) may impair filling by decreasing coordinated active relaxation or by simply decreasing the total filling time. • Tricuspid stenosis and mitral stenosis result in increased measured CVP and PAOP, respectively, while RVEDP and LVEDP may remain normal (valvular stenosis creates a pressure gradient and violates the assumptions required for CVP and PAOP approximate RVEDP and LVEDP, respectively). • External compression from pericardial effusion, positive end-expiratory pressure (PEEP), tension pneumothorax, pleural effusions, or greatly increased abdominal pressures may reduce passive ventricular compliance. • Intraventricular filling defects (tumors and clots) and septal shifts causing ventricular

interdependence (severe pulmonary hypertension, high levels of PEEP, and RV infarction) may restrict diastolic filling of cardiac chambers. • Surrogate filling pressures (CVP and PAOP) cannot reliably discern diastolic dysfunction from systolic dysfunction. In several studies in critically ill patients, volume assessment via transesophageal echocardiography disagreed with static pulmonary artery catheter pressure assessments in up to 55% of patients and significantly altered medical management in 32– 44% of those patients (5)[B].

PERIOPERATIVE RELEVANCE

• Volume responsiveness refers to the ability of an increase in preload (volume challenge) to produce a clinically significant increase in stroke volume (resulting in increased blood pressure and cardiac output). – Ongoing volume responsiveness suggests that the LV is still on the upslope of the Frank– Starling curve (increased LVEDP generates the expected increased ventricular contractility). – Lack of volume responsiveness suggests that the LV has “fallen off” the Frank–Starling curve (meaning increased LVEDP no longer generates increased contractility). • Many pathophysiologic processes disrupt the normal relationship between measured filling pressures and actual preload volumes, making appropriate interpretation of filling pressures difficult.

EQUATIONS

• SV = EDV – ESV; where SV is stroke volume, EDV is end diastolic volume, and ESV is end systolic volume • Ejection fraction = [(EDV – ESV)/EDV] • Stroke volume variation (SVV) = [(SVmax − SVmin)/SVmean] where SV is proportional to the area under the pulse contour curve

REFERENCES

1. Hofer CK, Senn A, Weibel L, et al. Assessment of stroke volume variation for prediction of fluid responsiveness using the modified FloTrac and PiCCOplus system. Critical Care. 2008;12:R82. 2. Cannesson M, Desebbe O, Rosamel P, et al. Pleth variability index to monitor the respiratory variations in the pulse oximeter plethysmographic waveform amplitude and predict fluid responsiveness in the operating theatre. Br J Anaesth. 2008;101:200–206. 3. Michard F, Boussat S, Chemla D, et al. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med. 2000;162:134–138. 4. Feissel M, Michard F, Faller JP, et al. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med. 2004;30:1834–1837. 5. Beaulieu Y. Bedside echocardiography in the assessment of the critically ill. Crit Care Med. 2007;35:S235–S249.

ADDITIONAL READING

• Bar-Yosef S, Schroeder RA, Mark JB. Hemodynamic Monitoring. In: Longnecker et al., eds. Longnecker DE, Brown DL, Newman MF, et al. Anesthesiology. New York, NY: McGraw-Hill Medical; 2008:519–551. • Chappell D, Jacob M, Hofman-Keifer K, et al. A rational approach to perioperative fluid management. Anesthesiology. 2008;109:723–740.

See Also (Topic, Algorithm, Electronic Media Element) • Positive end expiratory pressure (PEEP) • Left ventricular end diastolic pressure

CLINICAL PEARLS

• Echocardiographic assessment of EDV is the gold standard for preload determination. When echocardiography is performed to optimize preload, the filling pressures required to achieve that desired preload should be noted and maintained (although compliance may still change over time). • Dynamic pressure changes (both arterial and venous) in response to fluid challenges are better guides to ongoing fluid resuscitation than static preload pressure surrogates (CVP/PAOP). • During positive pressure mechanical ventilation, the SVV induced by the heart–lung interaction is a more reliable assessment of volume responsiveness than static filling pressure. – CVP/PAOP should always be measured during the passive exhalation phase of the respiratory cycle to avoid artifactual changes due to active inspiratory forces (PEEP transmitted during this exhalation will still elevate the measured filling pressures). – Due to higher intrathoracic pressures, positive pressure ventilation (especially with higher PEEP) impedes diastolic ventricular filling, so higher filling pressures (CVP/PAOP) are then required to maintain the normal preload. • Measures of preload or volume responsiveness do not necessarily indicate volume need. If a patient is normotensive with presumed normal cardiac output as measured by the end organ function (e.g., urine output), conservative fluid management is likely appropriate regardless of SVV or CVP. • Expect the need for higher filling pressures to maintain normal/adequate EDV in patients suspected of LVH. In the absence of echocardiography, LVH may be clinically suspected in hearts that have been working against high afterload over many years (e.g., chronic poorly treated hypertension or morbid obesity) or when high voltage changes are seen on the electrocardiogram. • While low filling pressures (CVP/PAOP) are generally associated with suboptimal filling volumes (i.e., additional volume responsiveness), high filling pressures often correlate poorly with filling volumes (due to coexisting pathophysiology or measurement difficulties). Confidence in the presumed pressure–volume relationships should decrease as measured filling pressures increase (echocardiography or dynamic preload measures should be considered for confirmation of preload status when deciding to restrict further fluids due to

high CVP/PAOP measurements).

PREMATURE ATRIAL CONTRACTIONS Dwayne E. McClerklin, MD

BASICS DESCRIPTION

• Premature atrial contractions (PACs) describe the initiation of a discordant atrial contraction by an ectopic atrial pacemaker focus. • In the perioperative period, PACs are seen – In patients with a chronic, baseline occurrence (most common) – In response to hypoxia, hypercarbia, or metabolic derangements (e.g., hypokalemia, hypomagnesemia). EPIDEMIOLOGY Prevalence

Information not available Prevalence

Very common and often asymptomatic; therefore, difficult to quantify with any accuracy. Morbidity

• In isolation, PACs usually do not indicate heart disease. • Under certain circumstances, premature atrial depolarizations may trigger re-entrant tachycardias or atrial fibrillation. Atrial fibrillation is the most common secondary dysrhythmia associated with premature atrial depolarizations. Mortality

Not fatal intrinsically; however, death can occur from the secondary arrhythmia. ETIOLOGY/RISK FACTORS

• Extremes of age • Excessive caffeine consumption • Hyperthyroidism • Alcohol abuse • Tobacco abuse • Chronic lung disease • Ischemic heart disease • Digitalis toxicity • Anxiety • Pregnancy • Perioperative causes – Hypoxia

– Hypercarbia – Sympathetic stimulation – Metabolic abnormalities Hypokalemia Hypomagnesemia Hypercalcemia • Following cardioversion

PHYSIOLOGY/PATHOPHYSIOLOGY

• Pacemaker cells: Spontaneous (phase 4) diastolic depolarization conveys the property of automaticity (pacemaking) that is characteristic of cells in the following: – Sinoatrial (SA) node: Action potentials are characterized by a membrane potential of –40– 60 mV (vs. –85 mV in the ventricular myocyte), slow and spontaneous phase 4 upstroke, and rapid phase 0 depolarization after the threshold potential is reached. – Atrioventricular (AV) nodes – His–Purkinje system – Cells surrounding the coronary sinus – Cells surrounding the pulmonary veins • Hierarchy: The intrinsic rates of depolarization in cardiac pacemakers are greatest in atrial pacemakers, followed by AV junctional pacemakers, followed by ventricular pacemakers. – The sinoatrial node (SA), located at the junction of the right atrium and superior vena cava, functions as the primary pacemaker of the heart. It displays the highest intrinsic rate of action potential discharge at 80–100 bpm. – Packemaker cells in the AV node may initiate an action potential if the SA node is not functioning properly. Consequently, pacemaker cells in the ventricle may initiate an action potential in the event that the SA and the AV node do not fire. • P wave: The action potential generated by the SA node is transmitted rapidly through the atria, to the AV node, and is the source of the P wave seen on the ECG. • Autonomic nervous system: Dynamically regulates the rate of phase 4 depolarization and, therefore, the firing rate of pacemaker cells. • Premature atrial depolarization and contraction: A known or unknown eliciting factor results in an ectopic atrial depolarization that occurs prior to SA node depolarization; it fires early and out of turn, subverting the hierarchy. The premature depolarization can then, in a domino-like fashion, depolarize adjacent cells in the atrium, travel to the AV node, and produce a normal ventricular depolarization. Consequently, a premature mechanical contraction will result. • Premature atrial depolarization and abnormal accessory tracts: A circus rhythm may result in patients with abnormal pathways that connect the atria and ventricles (normally, the AV node is the only connection between the atria and ventricles). – If the accessory pathway is still refractory when the premature atrial depolarization encounters it, then the impulse will conduct normally through the AV node. – However, if the premature atrial depolarization impulse encounters the accessory pathway when it is out of its refractory period, it can result in a self-sustaining “circus rhythm.” Antidromic tachycardia: When the accessory tract is excited in the atria, conduction to the ventricles is via the accessory node. Subsequent atrial depolarization occurs from

retrograde transmission (ventricles to the atria) via the AV node. A widened QRS complex is seen on the EKG. Orthodromic tachycardia (more common): When the accessory tract is excited in the ventricles, retrograde transmission (ventricles to the atria) is via the accessory tract and subsequent atrial depolarization occurs through the AV node. A normal width QRS is seen on the EKG.

PREVENTATIVE MEASURES

• Maintenance of physiologic acid-base status as well as avoidance of hypoxia, hypercarbia, electrolyte derangements, and sympathetic stimulation. • Anxiolysis • Treatment of underlying chronic condition • Avoidance of alcohol use, tobacco use, and caffeine consumption.

PREOPERATIVE ASSESSMENT • Intraoperatively: – Early P wave of different sizes, shapes, or axes than the patient’s sinus P wave complex. However, if the ectopic focus occurs near the atrial pacemaker, the P wave may appear identical to the patient’s normal sinus P wave. – The P–R interval varies. Premature atrial depolarizations that originate near the AV node may feature a shortened PR interval due to the proximity of the ectopic focus to the AV node. A longer P–R interval may be seen if the premature atrial depolarization reaches the AV node during the relative refractory period. If the premature atrial depolarization reaches the AV node during the absolute refractory period, it is not conducted. It appears as an isolated P wave. – QRS complexes are normal and narrow; they are conducted normally via the AV node and through the right and left bundle branches. – Aberrant, wide QRS complexes may be seen when the premature atrial depolarization is conducted to ventricular tissue before complete repolarization has occurred. – Compared to premature ventricular depolarizations, premature atrial depolarizations are not associated with a full compensatory pause. • Awake or outpatient setting. – Symptoms: Often asymptomatic; patients who are symptomatic endorse a “wavering” heartbeat or a “skipped” beat. – Holter monitoring is the most sensitive method of diagnosing PACs.

DIFFERENTIAL DIAGNOSIS

• Premature ventricular depolarizations: Lack an associated P wave complex and feature a full compensatory pause prior to initiation of the successive depolarization. • Sinus arrhythmia: Features normal sinus P waves and P–R intervals and 1:1 AV conduction. Sinus arrhythmia may be associated with inspiration and expiration. • Digitalis effect: The ECG demonstrates ST segment sloping and a regular rhythm.

TREATMENT • Rule out hypoxia, hypercarbia, myocardial ischemia, sympathetic stimulation (pain, awareness), and metabolic abnormalities. If present or suspected, therapy should be aimed at the underlying cause. • Determine hemodynamic stability. – Stable: No treatment is required. – Unstable: Beta-blockade and calcium channel blockers may be necessary. • Chronic therapy: Ranolazine is a novel antianginal agent that alters the trans-cellular Na+ current and has been shown to be effective in terminating premature atrial depolarizations.

FOLLOW-UP • For intraoperative PACs, inform the patient’s family if the PACs were associated with hemodynamic instability or anesthetic cause. • Hemodynamic causes: If from hypoxia, hypercarbia, hypotension, hypertension, or ischemia, ensure that the underlying cause has been treated and resolved. • If the intraoperative PACs were secondary to an anesthetic cause, careful examination of the intraoperative anesthetic record may provide information regarding the potential triggering agents or conditions. Documentation of the findings is warranted to prevent recurrence or replication of the onset of PACs. • Consider a telemetry bed, particularly if associated with hemodynamic instability.

REFERENCES

1. Perez MV, Dewey FE, et al. Electrocardiographic predictors of atrial fibrillation. Am Heart J. 2009;158:622–628.

2. Sosalla S, Wagner S, et al. Altered Na+ currents in atrial fibrillation: Effects of ranolazine on arrhythmias and contractility in human atrial myocardium. J Am Coll Cardiol. 2010;55:2330–2342. 3. Narayan SM, Kazi D, et al. Repolarization and activation restitution near human pulmonary veins and atrial fibrillation initiation: Mechanisms separating persistent from paroxysmal atrial fibrillation. J Am Coll Cardiol. 2008;52: 1222–1230. 4. Stein PK, Barzilay JI, et al. Heart rate variability and its changes over 5 years in older adults. Age Ageing. 2009;38:212–218. 5. Folkeringa RJ, Hartgers J, et al. Atrial extrasystoles after exercise predict atrial fibrillation in patients with left ventricular hypertrophy. Heart. 2006;92:545–546. See Also (Topic, Algorithm, Electronic Media Element) • Premature ventricular contractions • Pacemaker cells of the heart

CODES

ICD9

427.61 Supraventricular premature beats ICD10

I49.1 Atrial premature depolarization

CLINICAL PEARLS

• Premature atrial depolarizations are commonly benign dysrhythmias. They can, however, trigger a circus rhythm via an accessory tract or atrial fibrillation (rare). • Intervention is warranted only if there is an associated compromise in hemodynamic stability. • Beta blockers and calcium channel blockers are the most commonly used agents to terminate PACs in the event of hemodynamic compromise.

PREMATURE VENTRICULAR CONTRACTIONS J. Aaron Williams, MD

BASICS DESCRIPTION

• Premature ventricular contractions (PVCs) describe a discordant ventricular contraction that is caused by an ectopic ventricular pacemaker focus. PVCs are also referred to as ventricular premature beats (VPBs) and ventricular extrasystoles. • Although PVCs can be a common, non-pathologic occurrence, the new onset or an increased frequency in the perioperative period should alert the anaesthetist to the possibility of ominous underlying pathology: – Hypoxia – Hypercarbia – Acidosis – Myocardial ischemia EPIDEMIOLOGY Prevalence

• True incidence is hard to ascertain secondary to most being asymptomatic at onset and over time. • Increases primarily with age. • Predilection toward males, and African Americans (vs. Caucasians).

Prevalence

• Numbers vary greatly with the length of the monitoring period; longer periods result in a much higher detection rate (e.g., single EKG versus 2 minute EKG versus 24-hour Holter monitoring). • PVCs are detected in at least 50% of young men and women (on 24-hour Holter monitoring) (1,2). • Elderly patients in one study had a nearly 30% incidence of >30 PVCs/hr (Lown classification 2) (3). Morbidity

• Palpitations causing distress, or uncommonly, pre-syncopal or syncopal episodes. • Related to underlying condition. • Bigeminy, over time, can lead to cardiomyopathy irrespective of other disease processes (4).

Mortality

• Related to the underlying condition or progression to more malignant arrhythmias. • Increased mortality has been associated with: – Increased frequency/number

– Multiform waves – Runs of PVCs (couplets, NSVT) – Complex arrhythmias during exercise, and particularly after exercise (5).

ETIOLOGY/RISK FACTORS

• Perioperative – Normal variant – Hypoxemia – Hypercarbia/acidosis – Myocardial ischemia/infarction – Pulmonary embolism – Electrolyte imbalance: Hypokalemia, hypomagnesemia, and hypercalcemia (can result from intraoperative furosemide, mannitol, and IV contrast dye) – Any high-catecholamine state – Medications: Epinephrine, norepinephrine, dopamine, digoxin, tricyclic antidepressants, aminophylline, other anti-arrhythmic agents (flecainide, etc.) – Bradycardia – Anxiety – Localized irritation/mechanical factors: Central venous line introducer wire or catheter, pulmonary artery catheter, surgical tools or hands in the operative field (particularly in open heart surgery as well as in thoracic surgery, Nuss procedures, etc.) • Chronic conditions: Hypertension, left ventricular hypertrophy, prior myocardial infarction, cardiomyopathy, and valvular heart disease • Provocative events: Exercise, smoking/nicotine exposure, caffeine and chocolate ingestion

PHYSIOLOGY/PATHOPHYSIOLOGY

• Three mechanisms in general: – Enhanced automaticity: Electrolyte disturbances and elevated-catecholamine states can affect the membrane resting potential/automaticity of ventricular pacemakers – Triggered activation: Ischemia, digoxin – Re-entrant phenomenon: Ischemic pathways or old infarcts can delay normal impulse conduction and cause delayed firing that is “off-cycle” or “out-of-sync.” • May originate from one focus or multiple foci within one or both ventricles (i.e., outside the SA–AV-nodal or His–Purkinje systems) • Hemodynamic concerns: – Can cause hemodynamic instability; the lack of an atrial kick during ventricular diastole can decrease the stroke volume and cardiac output (particularly with bigeminy or frequent PVCs). – Although commonly benign in nature, may signify a more sinister underlying disorder. – May progress to malignant dysrhythmias in certain conditions (6).

PREVENTATIVE MEASURES

• In the operating room, avoid hypoxemia, hypercarbia/acidosis, hypotension or tachycardia (myocardial ischemia), and other above-mentioned causes. – Chronic beta-blocker therapy may be appropriate in certain settings (i.e., symptomatic,

post-MI arrhythmias, etc.) (7). • Outpatient setting: Avoid caffeine, nicotine, alcohol, and chocolate, as well as herbals and diet pills containing stimulants (pseudoephedrine, etc.).

PREOPERATIVE ASSESSMENT Intraoperatively

• Primarily an EKG diagnosis: Level 1A (7) – Premature ventricular depolarization – No P wave (as seen with a premature atrial depolarization/contraction) – Irregular, wide-complex QRS – Compensatory pause takes place prior to the next normal beat. – R–R interval of surrounding beats is usually constant – If multifocal, it will show various QRS morphologies. • Pulse oximeter or arterial line waveform can be observed to rule out electrical artifact, patient movement, or movement around the patient. If it is “real” one would see an irregularly placed pulsation/beat with a smaller waveform (amplitude). • Initial diagnostic tests – 12-lead EKG would be helpful if new-onset ischemia is suspected – Arterial blood gas to check for acidosis, hypoxia, hypercarbia – Electrolyte studies – Initial cardiac enzymes if ischemia is suspected • Other diagnostic tests: – CXR if a central venous line or retained wire is suspected – Digoxin level (if applicable) – Urine drug screen – Echocardiogram Awake or outpatient setting: • History – Many are asymptomatic – Can be associated with palpitations (from the augmented beat after the PVC) or a “pause” in the heartbeat from non-sustained ventricular tachycardia (NSVT) or ventricular tachycardia (VT) – Previous presyncopal or syncopal episodes from bigeminy or progression to NSVT/VT – Presence on the preoperative EKG; however, it is more likely to be detected on intraoperative EKG (longer duration of monitoring than preoperative 10-second EKG) • Diagnostic tests – 24-hour Holter monitoring: Level 1A (7) – Cardiac stress testing – Coronary angiography – Electrophysiologic testing • Lown classification system: (8) – 0 = No PVCs – I = <30 PVCs/hr

– II = ≥30 PVCs/hr – III = Multiform PVCs – IVa = Couplets (normal beat followed by two PVCs sequentially) – IVb = Ventricular tachycardia (≥3 PVCs sequentially)

DIFFERENTIAL DIAGNOSIS

• EKG artifact from motion (patient or other people touching the patient) • EKG artifact from electrocautery or ESWL • Premature atrial contractions • Sinus pauses • Second-degree type I or II heart block • Third-degree heart block

TREATMENT • Management involves concurrent correction or treatment of the underlying cause as well as ensuring hemodynamic stability. – Stable: If new-onset, investigate for ominous causes. If absent, remain vigilant to possibly detect any secondary causes. – Unstable: Consider stopping the surgical interventions (pneumoperitoneum, pericardial manipulation, etc.), and/or finishing/canceling the case. Consider implementing the BLS/ACLS algorithms (i.e., defibrillation for pulseless VT, etc.). • Treat secondary causes as appropriate: – Electrolyte replacement – Ventilator changes for respiratory acidosis – Central venous line manipulation if it is in too deep. – Optimizing myocardial oxygen supply and demand if acute coronary syndrome or ischemia may be present. • Symptomatic treatment: Suppression of PVCs in the perioperative period with lidocaine or metoprolol may aid with hemodynamic stability. However, there are no studies on this particular scenario and, thus, it should not delay the above-mentioned therapies.

FOLLOW-UP • If a history of pre-syncope or syncope is uncovered preoperatively, one may consider cardiology evaluation prior to elective procedures. • If new onset occurs intraoperatively, a cardiology consult, telemetry monitoring, and/or further diagnostic tests may be warranted depending on the history and situation. • Patients with malignant arrhythmias or frequent PVCs may benefit from ablation therapy (7).

REFERENCES

1. Brodsky M, Wu D, Denes P, et al. Arrhythmias documented by 24-hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart

disease. Am J Cardiol. 1977;39:390–395.

2. Sobotka PA, Mayer JH, Bauernfeind RA, et al. Arrhythmias documented by 24-hour continuous ambulatory electrocardiographic monitoring in young women without apparent heart disease. Am Heart J. 1981;101:753–759.

3. Glaser SP, Clark PJ, Appelbaum HJ. Occurrence of frequent complex arrhythmias detected by ambulatory monitoring. Chest. 1979;75:565–568. 4. Chugh SS, Shen WK, Luria DM, et al. First evidence of premature ventricular complexinduced cardiomyopathy: A potentially reversible cause of heart failure. J Cardiovasc Electrophysiol. 2000;11(3):328–329.

5. Dewey FE, Kapoor JR, Williams RS, et al. Ventricular arrhythmias during clinical testing and prognosis. Arch Intern Med. 2008;168:225–234. 6. Dalal D, Nasir K, Bomma C, et al. Arrhythmogenic right ventricular dysplasia: A United States experience. Circulation. 2005;112:3823–3832. 7. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines. Circulation. 2006;114:e385–e484. 8. Lown B, Wolf M. Approaches to sudden death from coronary heart disease. Circulation. 1971;44:130–142. See Also (Topic, Algorithm, Electronic Media Element) • Ventricular tachycardia • Intraoperative hypoxia

CODES ICD9 427.69 Other premature beats ICD10 I49.3 Ventricular premature depolarization

CLINICAL PEARLS

• PVCs can represent a varied clinical picture from benign to suggestive of severe pathology. • Uncommonly, they may progress to more malignant arrhythmias. • Treatment revolves around identifying and treating the underlying disease process. • Uncommonly, direct treatment of PVCs is indicated (beta-blockers, ablation).

PRERENAL ACUTE KIDNEY INJURY Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Acute renal failure (ARF), also known as acute kidney injury (AKI), is characterized by a rapid decline in the glomerular filtration rate (GFR), accompanied by azotemia with, or without, oliguria. • Prerenal AKI describes the loss of kidney function secondary to the flow of blood before it reaches the kidneys; it is also termed prerenal azotemia. This differs from renal AKI that affects the kidney itself and postrenal AKI where the movement of urine out of the kidneys is impaired. Prerenal AKI is the most common cause of ARF and can result from: – Decreased blood volume – Low blood flow states – Interrupted blood flow to the kidneys • Early recognition and treatment of underlying causes is critical, as prerenal AKI is usually reversible EPIDEMIOLOGY Prevalence

• Varies widely across studies and patient population. • All cause AKI may be seen in ∼5–8% of hospitalized patients and ∼50% of ICU patients. • Prerenal causes are estimated to comprise ∼75% of AKI cases.

Morbidity

AKI (all cause) can result in: • Fluid overload • Electrolyte imbalance • pH abnormalities • Impaired metabolism/clearance of drugs • Impaired excretion of waste products (uremia) Mortality

Although most patients who develop prerenal AKI have complete recovery of their kidney function, they have a greater than two-fold increase in in-hospital mortality. ETIOLOGY/RISK FACTORS

• Causes of prerenal AKI can be classified as: – Low volume states: Hypovolemia (burns, edema, diarrhea, vomiting, hemorrhage, dehydration) – Low perfusion states: Hypotension, shock (cardiac, septic, anaphylactic), cirrhosis, drugs

(ACE inhibitors, NSAIDs) that decrease glomerular capillary perfusion – Interrupted blood flow to the kidneys: Renal artery stenosis or embolus, trauma to the kidney, aortic cross clamping • There is an increased risk for prerenal AKI in: – Critically ill patients – Patients who are exposed to nephrotoxic agents (intravenous contrast, aminoglycosides, NSAIDs, etc.) – Patients with pre-existing renal disease

PHYSIOLOGY/PATHOPHYSIOLOGY

• Determinants of renal blood flow (RBF): – Cardiac output: The kidney receives ∼20% of the cardiac output; this is equivalent to 1 L/min in a 70 kg adult. The kidneys not only have a high metabolic requirement, but they also function as a filtering and homeostatic organ. – Renal perfusion pressure is dependent on the mean arterial pressure (MAP) in the renal artery and vascular resistance of the renal arterioles, primarily the afferent and efferent arterioles. – Autoregulation (intrinsic mechanism) of the RBF and GFR blunt the otherwise deleterious effects of variable blood pressure; it does not entirely negate the changes. Within MAPs of 80–180 mm Hg, RBF and GFR are relatively constant. Autoregulation occurs via two mechanisms: A myogenic response of vascular smooth muscle (fast response to stretch) and tubuloglomerular feedback (vasoconstrictive transmitters released by salt-sensing cells within the macula densa). – Extrinsic factors (humoral and nervous system): Bidirectional regulatory influences occur between the vasoconstrictor and vasodilatory hormonal systems. Renin–angiotensin–aldosterone feedback mechanism Antidiuretic hormone (ADH) Sympathetic system/adrenergic activity It appears that adrenergic activity and angiotensin II are the dominant influences that independently and synergistically impact the determinants of glomerular filtration. Interactions between the two are complex and significant. • Reduced renal perfusion stimulates intrinsic and extrinsic regulatory mechanisms in an attempt to compensate and maintain the GFR. • Early stages: – Renal parenchyma usually remains intact and functional – Lab tests demonstrate sodium reabsorption and urine concentration; FENa <1% • Sustained decreases in blood flow: – The time to, and level of, decrease varies widely amongst patients – Typically, a complete lack of blood flow for 30–60 minutes can result in permanent, irreversible cell damage; results in a secondary intrarenal AKI (acute tubular necrosis) • Severe hypoperfusion results in selective vasoconstriction of the renal and splanchnic beds in order to preserve perfusion to the brain and heart.

PREVENTATIVE MEASURES

• The cornerstone of treatment is prevention, prevention, and prevention. Goal-directed

therapy that optimizes preload, afterload, and contractility with fluids, vasopressors/inotropes, and blood transfusions may decrease the development of AKI. • Low blood volume requires volume resuscitation. – Carefully monitor insensible and blood losses, as well as urine output in the perioperative period so that interventions can be made early and preemptively. – Volume status assessment is a clinical judgment that is based upon vital signs (heart rate, blood pressure), monitors (urine output, arterial line variation, central venous pressures, pulmonary artery catheter measurements, echocardiogram), and physical examination (mucus membranes, capillary refill). – Replacement may be with isotonic crystalloid or colloid solutions and possibly blood. Controversy surrounds the best modality and outcome studies. – Excessive fluid resuscitation may lead to abdominal compartment syndrome and impaired renal perfusion. – Normal saline given in volumes greater than 30 mL/kg can cause a non-gap hyperchloremic metabolic acidosis and hyperkalemia. Hyperchloremia may decrease RBF, GFR, and urine output. • Low blood flow states require interventions to restore renal perfusion. – Treatment or optimization of the underlying etiology is key. – Autoregulation maintains a constant RBF between MAPs of 80–160 mm Hg; however, this curve may be shifted to the right in chronic hypertensives and thus require higher pressures. – Consider the use of inotropic medications and vasoconstrictors, as appropriate, to facilitate forward flow and perfusion. • Renal protection: The use of pharmacologic agents such as dopamine, fenoldopam, statins, and bicarbonate are aimed at decreasing potential intraoperative pathology. However, these agents have not consistently been shown to prevent or decrease AKI. • Avoid potential renal insults: Nephrotoxic agents such as iodinated contrast agents, NSAIDS, ACE inhibitors, and aminoglycoside antibiotics.

PREOPERATIVE ASSESSMENT • The RIFLE/AKIN classification has standardized the definition of renal failure. • Prerenal disease is distinguished by: – Urinalysis that is usually normal; positive ketones may be present – BUN/Cr ratio of >20:1; the decrease in flow to the kidneys results in more time for BUN to be reabsorbed. – Urine sodium <20 mEq/L – FENa <1% – Urine osmolality > 500 mOsm/kg • Note that the laboratory values in isolated prerenal AKI reflect “normal” renal function that attempts to conserve sodium and concentrate urine

DIFFERENTIAL DIAGNOSIS

Although causes of AKI are differentiated into prerenal, intrarenal, and postrenal, AKI with resultant acute tubular necrosis is commonly the consequence of multiple insults.

TREATMENT • Based upon treating the underlying cause. • Consider invasive monitoring with arterial line and central venous pressure or pulmonary artery catheter in order to provide goal-directed therapy. – Volume repletion with crystalloid, colloid, or blood. Caution should be exercised to avoid over-hydration with resultant tissue edema. – Improve cardiac function/output – Support renal perfusion pressure • In patients that develop intrarenal failure – Renal replacement therapy (RRT) – Dopamine and loop diuretics have not been shown to improve recovery, decrease the need for RRT, or improve survival.

FOLLOW-UP • Kidney function should return to normal within 24–72 hours

REFERENCES

1. houdhury D.Acute kidney injury: Current perspective. Postgrad Med. 2010;122:29–40. 2. Bagshaw SM, Bellomo R. Acute kidney injury in critical illness. Can J Anesth. 2010;57:985–998. 3. Liano F, Pascual J. Epidemiology of acute renal failure: A prospective, multicenter, community-based study. Kidney Int. 1996;50: 811–818. 4. Blantz RC, Singh P. Analysis of the prerenal contributions to acute kidney injury. Contrib Nephrol. 2011;174:4–11. 5. Kramer HJ, Horacek V, Backer A, et al. Relative roles of nitric oxide, prostanoids and angiotensin II in the regulation of canine glomerular hemodynamics. A micropuncture study. Kidney Blood Press Res. 2004;27(1):10–7. See Also (Topic, Algorithm, Electronic Media Element) • Glomerular filtration rate • Intrarenal disease • Postrenal disease • Renal blood flow

CODES ICD9 584.9 Acute kidney failure, unspecified ICD10

N17.8 Other acute kidney failure

CLINICAL PEARLS

• Prerenal azotemia (and postrenal AKI) “spare” damage to the kidney tissue compared to intrarenal causes. Laboratory values of prerenal disease, thus, reflect the kidney’s (maintained) ability to conserve sodium and concentrate urine. • Severe azotemia can lead to decreased protein binding and increased effect for some anesthetic agents.

PRESSURE–VOLUME LOOPS Emily K.B. Gordon, MD

BASICS DESCRIPTION

• Ventricular pressure–volume loops depict the relationship between pressure and volume in the left ventricle (LV). They aid with assessment of preload, contractility, and afterload as well as other physiologic parameters. • Commonly used techniques to acquire this data include left heart catheterization (direct measurements) and pulmonary artery catheters (extrapolation). PHYSIOLOGY PRINCIPLES

• The pressure–volume relationship delineates a single cardiac cycle. This is comprised of four basic phases: – Phase a (Points 4–1): Ventricular filling: Begins with the mitral valve open and blood from the left atrium passively enters the ventricle. This is followed by the atrial kick and ends with mitral valve closure. – Phase b (Points 1–2): Isovolumetric contraction: Begins with the mitral and aortic valve closed and contraction without ejection of blood. It ends with aortic valve opening. – Phase c (Points 2–3): Ejection: Begins with the aortic valve open and blood being propelled into the systemic circulation. It ends with aortic valve closure. Note that electromechanical diastole begins during ejection of blood from the aorta; the ventricle begins to relax and the aortic valve does not close until the LV pressure drops below aortic pressure. – Phase d (Points 3–4): Isovolumetric relaxation: Begins with the mitral and aortic valve closed and relaxation of the ventricle without a change in volume. It ends with mitral valve opening.

• Preload is depicted by the end diastolic volume (EDV; Point 1). • Afterload is represented by the pressure at the end of isovolumetric contraction (Point 2). • Inotropy can be assessed by the end-systolic pressure–volume relationship (ESPVR). The ESPVR curve becomes steeper and shifts to the left as inotropy (contractility) increases. • Stroke volume is represented by the difference between the EDV and end-systolic volume (ESV).

• Left ventricular compliance is depicted by the reciprocal of the slope seen at end-diastole (Point 1); this is called the end-diastolic pressure–volume relationship (EDPVR). • Stroke work (SW) describes the work performed by the ventricle to eject the stroke volume into the aorta. It can be assessed by the area within the pressure–volume loop or pressure– volume area (PVA) (Points 1–4). This combines the external stroke work (SW) with the potential energy (PE) remaining at the end of systole. Myocardial oxygen consumption can

be estimated by the PVA (recall that the primary determinants of VO2 are preload,

afterload, and contractility).

ANATOMY

• The ventricle is best described as an ellipsoid shape and its volume is best described by the geometric formula V = 4/3πr3, where r is the radius.

DISEASE/PATHOPHYSIOLOGY

• Systolic dysfunction signifies a loss of inotropy. – End-diastolic volume (preload): Increase

– ESV: Increase – Stroke volume: Decrease – Inotropy: Decrease; ESPVR slope decreases and shifts rightwards – Compliance: A dilated ventricle will exhibit an increase; EDPVR slope will decrease and shift rightward – Afterload: For any given afterload, there is a decreased velocity of fiber shortening – Stroke work: Decreased – Tension: Increase • Diastolic dysfunction signifies a decrease in ventricular filling secondary to hypertrophy or impaired relaxation (decreased lusitropy). – End-diastolic volume (preload): Decrease – ESV: Decrease or no change – Stroke volume: Decrease – Inotropy: No change or increases – Compliance: Decrease; EDPVR slope will increase – Afterload: Increases when secondary to hypertrophy – Stroke work: Decreased secondary to a decrease in stroke volume – Tension: Decrease

• Aortic stenosis (AS): The narrowing of the LVOT requires the LV to generate a much higher pressure in order to create an adequate stroke volume per each ventricular contraction. The amount of pressure that the LV must generate to create an adequate stroke volume is dependent on the degree of stenosis and the flow rate across the valve. Chronically, the total coronary flow increases in proportion to the increased LV wall stress and mass, but eventually, adequate subendocardial flow becomes difficult to attain leading to ischemia. – End-diastolic volume (preload): Increases acutely – ESV: Increase (to a greater extent than EDV) – Stroke volume: Decrease – Inotropy: Increases; slope of ESPVR increases and shifts leftward

– Compliance: Decreases; slope of EDPVR increases secondary to the left ventricular hypertrophy that is typically associated with AS – Afterload: Increase – Stroke work: Decrease – Tension: Increase • Mitral stenosis (MS) is marked by the pathologic obstruction of flow from the left atrium to the LV. This obstruction results in elevated LA pressure and pulmonary pressures. There is a

decrease in stroke volume secondary to a decrease in end-diastolic volume (preload). This decrease in preload leads to a decrease in cardiac output (CO) and aortic pressure, particularly aortic diastolic pressure. – End-diastolic volume (preload): Decrease – ESV: Decrease or no change – Stroke volume: Decrease – Inotropy: No change – Compliance: No change – Afterload: No change – Stroke work: Decrease

• Aortic regurgitation (AR), also known as aortic insufficiency (AI), is caused by the aortic valve not closing at the end of systolic ejection which allows blood to flow back from the aorta to the LV during the diastolic relaxation. As a result, there is no true LV isovolumic relaxation because blood is flowing back into the LV before the mitral valve even opens. – End-diastolic volume (preload): Increase – ESV: Initially, mild increase or no change; with failure, significant increase – Stroke volume: Initially, increase in stroke volume; if the ventricle goes into systolic failure, there is a decrease – Inotropy: Mild decrease or no change; does not change significantly in the chronic state – Compliance: Increase; slope of EDPVR decreases and shifts rightward

• Mitral regurgitation (MR) results in blood from the LV entering the left atrium during ventricular systole. This results in an increase in the LA’s volume and pressure during ventricular systole. There is no true isovolumetric contraction phase because as soon as the LV pressure exceeds LA pressure, blood flows backwards across the mitral valve and into the atrium. Additionally, there is no true isovolumetric relaxation because as the aortic valve closes and the ventricle relaxes, the MV remains open and blood flows back into the LA. This leads to an even smaller ventricular volume. – End-diastolic (preload): Increase – ESV: Small decrease or no change – Stroke volume: “Increase;” this is because the loop accounts for both the blood ejected forward into the aorta as well as the blood ejected back into the left atrium – Inotropy: No change or mild decrease – Compliance: Increases; the slope of EDPVR decreases and shifts rightward – Afterload: Decrease – Stroke work: Increase – Tension: Decrease

PERIOPERATIVE RELEVANCE

• Aortic stenosis – Prevent hypotension – Prevent events that decrease CO – Maintain normal sinus rhythm – Avoid tachycardia and bradycardia • Mitral stenosis – Maintain heart rate slightly lower to allow sufficient time in diastole and flow across the MV – Avoid atrial fibrillation in order to maintain the atrial kick – Carefully titrate fluid administration in order to avoid volume overload • Aortic regurgitation – Maintain HR >80 beats/min to avoid increased diastolic time and therefore LV overload – Avoid an increase in systemic vascular resistance (SVR) – Treat acute overload with vasodilators • Mitral regurgitation – Prevent events that would decrease CO – Maintain normal to fast heart rate – Afterload reduction – Maintain adequate preload EQUATIONS

• T = (ΔP × R)/2 h; where T is tension, ΔP is change in pressure, R is radius, and h is wall thickness. • EF = [EDV − ESV]/EDV = SV/EDV • Cardiac work = (stroke work) × (heart rate)

REFERENCES

1. Fonseca J, Andrade A, Nicolosi DE, et al. Cardiovascular simulator improvement: Pressure versus volume loop assessment. Artif Organs. 2011;35(5):454–458. 2. Andrews DT, Royse AG, Royse CF. Functional comparison of anaesthetic agents during myocardial ischaemia-reperfusion using pressure–volume loops. Br J Anaesth. 2009;103(5):654–664. 3. Sasayama S, Nonogi H, Sakurai T, et al. Assessment of cardiac function by left heart catheterization: An analysis of left ventricular pressure–volume (length) loops. J Cardiogr Suppl. 1984;(1):25–34. 4. Katz AM. Influence of altered inotropy and lusitropy on ventricular pressure–volume loops. J Am Coll Cardiol. 1988;11(2):438–445. 5. eremias A, Brown DL. Cardiac Intensive Care, 2nd edition. Philadelphia, PA: Elsevier; 2010 See Also (Topic, Algorithm, Electronic Media Element) • Contractility • Preload • Afterload

• Ejection fraction • Lusitropy

CLINICAL PEARLS

• Preload can be increased by giving intravenous fluids. • Stroke volume can be increased by instituting inotropic therapy and optimizing preload and afterload. • Afterload can be reduced with the use of vasodilators (i.e., calcium channel blockers, nitroglycerin, etc.).

PRETERM INFANT John T. Chalabi, MD Samuel H. Wald, MD

BASICS DESCRIPTION

The premature infant is defined as being born before 37 weeks of gestation. EPIDEMIOLOGY Prevalence

• Comprises 12.3% of all births in the US annually (1) • The highest rates are seen in non-Hispanic Americans and African Americans; and the lowest are seen in Asians or Pacific Islanders. Prevalence

Greater than 500,000 births Morbidity

• CNS: Intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP) • Cardiac: Patent ductus arteriosus (PDA) • Pulmonary: Respiratory distress syndrome (RDS), meconium aspiration syndrome, bronchopulmonary dysplasia (BPD), apnea of prematurity (AOP), persistent pulmonary hypertension • GI: Necrotizing enterocolitis (NEC), gastroesophageal reflux disease (GERD), jaundice/hyperbilirubinemia • Infectious: Bacterial sepsis • Metabolic: Hypoglycemia, hypocalcemia

Mortality

Although two-thirds of infant deaths in the US occur among infants born prematurely, only 17% of infant deaths are classified as being attributable to premature birth. ETIOLOGY/RISK FACTORS

• Birth defects • Maternal risk factors – History of premature birth – Twins, triplets, or other multiple pregnancy – Uterine or cervical abnormalities – Poor prenatal care – Smoking – Alcohol consumption

– Substance abuse – Select medication exposure – Physical, sexual, or emotional abuse – Infection – Hypertension and preeclampsia – Diabetes – Obesity or malnutrition – Short time period between pregnancies – In vitro fertilization – Vaginal bleeding – Non-Hispanic, African-American race – Extremes of maternal age (<17, >35) – Low socioeconomic status

PHYSIOLOGY/PATHOPHYSIOLOGY

• Nervous system – IVH has a 20–30% incidence in infants born <31 weeks and weighing <1,500 g at birth. – ROP has a higher incidence in lower post-conceptual age infants. Hyperoxia causes abnormal neovascularization. However, because normal photoreceptor development requires high levels of oxygen, the underdeveloped retinal vasculature cannot meet the oxygen demands and hypoxia-inducible factor and vascular endothelial growth factor are consequently released. These factors result in “neovascularization" with abnormal proliferation from the retina to the vitreous. Neovascularization can cause fluid leak, hemorrhage, and retinal scar formation with traction of the retina. In severe case it can cause retinal detachment. – Cognitive impairment is more likely. • Cardiovascular – A less compliant ventricle is more dependent on heart rate for cardiac output. – Decreased sensitivity to catecholamines. – Small absolute blood volume. – Underdeveloped baroreflex. – Higher incidence of PDA. • Respiratory – Low levels of surfactant cause RDS, ventilation/perfusion mismatch, and hypoxia. – Small airways are prone to obstruction (subglottic stenosis, laryngotracheomalacia). – There is an increased susceptibility to oxygen toxicity and barotrauma resulting in BPD from prolonged intubation. – Apnea of prematurity (AOP) reflects immaturity of the respiratory control system that manifests as an unstable respiratory rhythm. The neonatal neurotransmission pathway is underdeveloped and both central and peripheral chemoreceptors are impaired. The preterm neonate displays a reduced ventilatory response to hypercapnia; a biphasic response to hypoxia (initial increase in ventilation for 1 minute, followed by a phase of decreased ventilation; severely preterm infants typically do not display a period of hyperventilation); and an enhanced inhibitory response by upper and lower airway afferent innervation secondary to stimulation (i.e. negative pressure and positive airflow).

– Persistent pulmonary hypertension from persistent right-to-left shunt through a foramen ovale, PDA, or both. • Immune system: Increased susceptibility to infection is related to the immaturity of both cellular and hormonal aspects. • Renal function is dependent upon the post-conceptual age: A 28–30 week post-conceptual age infant has a GFR that is almost half that of a term infant. The initial creatinine value reflects the maternal creatinine and should decrease within 3–4 weeks. • Gastrointestinal: Preterm infants frequently have an immature gag reflex and are unable to coordinate sucking, swallowing, and breathing until 34–36 weeks post-conceptual age; this makes feeding difficult. • Metabolic – Temperature dysregulation can result from a lack of brown fat, high body surface area to body mass ratio, lack of adequate insulation, and high evaporation rate. – There is an increased risk of developing hypoglycemia due to immature hepatic glycogenolysis and adipose tissue lipolysis, hormonal dysregulation, and deficient hepatic gluconeogenesis and ketogenesis. – Anemia due to repeated phlebotomy, shortened RBC survival, rapid growth, and transition from fetal to neonatal life.

ANESTHETIC GOALS/GUIDING PRINCIPLES

Anesthetic goals should be centered around maintaining baseline ventilatory and circulatory status while providing an adequate level of analgesia, amnesia, and immobility.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Body hair (lanugo) • Abnormal breathing patterns (shallow, irregular pauses in breathing) • Enlarged clitoris (female infant) • Small scrotum, smooth without ridges, and undescended testicles (male infant) • Low muscle tone • Feeding problems • Soft, flexible ear cartilage • Thin, smooth, shiny skin

History

• Vital signs • Current weight and birth weight • Gestational and post-conceptual age • Type of delivery • Lung disease • Cardiovascular history (structural anomaly, history of apnea and/or bradycardia) • Presence of genetic abnormalities or other syndromes • Infections

Signs/Physical Exam

• The Ballard Score is a set of procedures developed by Dr. Jeanne L Ballard, MD to determine the gestational age through neuromuscular and physical assessment of a newborn fetus. It consists of multiple charts and diagrams with neonates in different postures; the combined score determines the gestational age. • Attention should also be given to the following: Hypotonia, respiratory distress, failure to thrive, temperature dysregulation, small for gestational age, jaundice, and anemia

TREATMENT HISTORY

History of treatment for specific conditions should be clarified and investigated, noting if the condition was treated completely, or if there are any residual effects, and if there are any physiologic changes from the disease. For instance: • Prolonged intubation • Cardiac failure/arrest, cardiac surgeries • Apnea • Seizures • IVH MEDICATIONS

The prescribed medications can alert the anaesthetist to a number of preexisting conditions: • Prostaglandin: PDA, pulmonary hypertension • Caffeine: Apnea • Vasopressors: Heart failure, septicemia • ACE inhibitors: Hypertension, heart failure • Digoxin: Right heart failure, hypertrophic obstructive cardiomegaly • Diuretics: Heart failure, acute renal failure, hypervolemia • Beta-blocker: Hypertrophic obstructive cardiomegaly DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Chemistry • Bilirubin level • Arterial or venous blood gas • Chest radiograph • Echocardiogram

CONCOMITANT ORGAN DYSFUNCTION See Pathophysiology

CIRCUMSTANCES TO DELAY/CONDITIONS

• Emergency cases should be done as the stability of the patient allows. • Elective cases should be postponed until apnea, the major risk of anesthesia, is reduced; this can last for up to 60 weeks post-conceptual age.

CLASSIFICATIONS

• Low birth weight infants: 1,500–2,500 g • Very low birth weight infants: 1,000–1,500 g • Extremely low birth weight infants: <1,000 g

TREATMENT PREOPERATIVE PREPARATION Premedications

Vagolytics may be used to reduce salivation and increase the heart rate (atropine, scopolamine, glycopyrrolate) Special Concerns for Informed Consent

The consent should detail the risks of anesthesia in the perioperative period and the possibility of post-operative ventilation, the post-anesthesia recovery plan, and any special concerns about the disease. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia is commonly used. • Regional techniques (caudal blocks, spinal anesthesia) as a sole technique may be used for lower abdominal and lower extremity procedures, particularly in infants that have developed BPD or are at increased risk of apnea.

Monitors

• ASA standard monitors. • Depending on the surgical procedure and comorbidities, an arterial line or central venous line may be needed. • Neuromonitoring: The train of four may not be reliable.

Induction/Airway Management

• Induction consists of appropriate preoxygenation, the possible administration of vagolytics, and the use of propofol, barbiturates, opioids, ketamine, benzodiazepines, and/or dexmedetomidine • Increased total body water increases the volume of distribution for muscle relaxants compared to older children and adults. • Airway considerations: In general, pediatric patients have a relatively small oropharyngeal space, higher larynx at the C3 level, anterior position of glottic opening, large head and tongue, and floppy epiglottis • Airway equipment – Oral airway size 000, 00, 0, 40 mm – Endotracheal tube (ETT) sizes 2.0–3.5 – Pediatric laryngoscope handle with Miller blade 00 or 0 – ETT usually secured at 6–9 cm at the gum

Maintenance

• Preterm infants have lower minimum alveolar concentration requirements compared to term infants. • Oxygen concentration should be kept as low as possible to reduce the possibility of ROP. • Active warming should be implemented during surgery with the knowledge that the preterm infant’s skin is more fragile and susceptible to burns.

Extubation/Emergence

• The patient should be fully awake and have full return of the neuromuscular function • Good respiratory effort • Stable hemodynamics • Acceptable body temperature • Equipment available for re-intubation

FOLLOW-UP BED ACUITY

Almost all preterm infants should be admitted to the neonatal intensive care unit, pediatric intensive care unit, or monitored bed for continuation of care, recovery, and detection of apnea up to 60 weeks post-conceptual age. MEDICATIONS/LAB STUDIES/CONSULTS

Labs should be ordered with consideration that blood draws in excess may cause anemia and prolong recovery.

REFERENCES

1. Martin JA, Osterman MJK, Sutton PD. Are preterm births on the decline in the United States? Recent data from the National Vital Statistics System. NCHS Data Brief. 2010;39:1– 8.

2. Goldenberg RL, Culhane JF, Iams JD, et al. Epidemiology and causes of preterm birth. Lancet. 2008;371:75–84. 3. Mathew OP. Apnea of prematurity: pathogenesis and management strategies. Journal of Perinatology. 2010;1–9.

ADDITIONAL READING • www.ballardscore.com

See Also (Topic, Algorithm, Electronic Media Element) • Apnea of prematurity • Anemia of prematurity • Retinopathy of prematurity • Patent foramen ovale

CODES ICD9

765.10 Other preterm infants, unspecified [weight] ICD10 P07.30 Preterm newborn, unspecified weeks of gestation

CLINICAL PEARLS

• Immaturity of the organ systems is the main concern for the anesthetic care of premature infants. • The increased risk of apnea in the perioperative period should be a consideration. • Prematurity affects both the pharmacokinetics and pharmacodynamics of the commonly used anesthetic agents.

PRETERM LABOR Shetal H. Patel, MD Sivam Ramanathan, MD Mark Zakowski, MD

BASICS DESCRIPTION

Preterm labor describes the onset of uterine contractions of sufficient strength and frequency to result in progressive cervical dilatation and effacement between 20 and 37 weeks of gestation. EPIDEMIOLOGY Prevalence

• Premature births have increased by 40% in the last 2 decades. • The highest rates of preterm births are in Africa (12%) and North America (11%), and the lowest rate is in Europe (∼6%). • In the US, 3.5% of births occur at <34 weeks of gestation • 30% of preterm labor resolves spontaneously. • 50% of women with preterm labor will deliver at term.

Morbidity

• Neonatal: – Long-term consequences: Mental retardation, developmental delay, cerebral palsy, seizure disorders, blindness, deafness, hyaline membrane disease, chronic pulmonary disease, and retinopathy of prematurity. – Infants delivered at <32 weeks gestation (∼2% of all births) account for the greatest amount of health care dollars spent on the neonate • Maternal morbidity is often associated with tocolytic therapy: – Magnesium sulfate: Respiratory arrest, cardiac arrest – Beta-agonists: Hypokalemia, hyperglycemia, cardiac arrhythmias, hypotension, pulmonary edema – Calcium channel blockers: Hypotension, headache, nausea Mortality

Preterm birth is the second leading cause of perinatal mortality after fetal anomalies. ETIOLOGY/RISK FACTORS

• Greater than 50% of preterm births occur in women who have no apparent risk factors. • A previous history of preterm labor is the most predictive risk factor. – 14% incidence in a subsequent pregnancy after one previous preterm delivery – 28% incidence in a subsequent pregnancy after two previous preterm deliveries

• Maternal characteristics (1): – African-American > Caucasian women – <18 years old or >35 years old – Lower socioeconomic status – History of tobacco use – History of cocaine or amphetamine use • Maternal anatomic features: – Uterine overdistention: Multiple gestations, polyhydramnios, macrosomia, and/or fibroids – Cervical dilatation >2 cm at 32 weeks – Short cervix – Bleeding after 12 weeks gestation • Surgical risk factors: – Abdominal surgery after the 1st trimester – History of surgery on the cervix – History of first or second trimester abortion • Infectious exposure: – Bacterial vaginosis – Pyelonephritis – Severe periodontal disease

PHYSIOLOGY/PATHOPHYSIOLOGY

• Inflammatory insults such as infections, ischemia, trauma, or allergic reactions incite the production of cytokines and prostaglandins. These inflammatory intermediates initiate uterine contractions and the release of proteases which damage the fetal membranes and decidua. • These events can result in cervical ripening, dilation, and possible rupture of membranes.

PREVENTATIVE MEASURES

Tocolytics are used to prolong gestation and enable fetal growth and development, as well as enable corticosteroids to exert a beneficial effect on fetal lung maturation. They are not recommended after 34 weeks gestation. • Calcium channel blockers (e.g., nifedipine) – Decreases the concentration of free calcium within the myometrium by blocking voltagedependent calcium channels in the cell membrane – Dose: Loading dose of 10 mg PO every 20 minutes until contractions stop to a maximum of 30 mg; then 10 mg PO every 6 hours – Maternal side effects: Vasodilation, headache, nausea – Fetal side effects: No direct effects • Prostaglandin synthetase inhibitors (indomethacin) – Inhibit production of prostaglandins F2α and E2α, which are potent stimulators of uterine activity – Dose: Loading dose of 50 mg PO then 25 mg PO every 6 hours for 48 hours – Maternal side effects: Gastric irritation, coagulation abnormalities (rare) – Fetal side effects: Premature closure of fetal ductus arteriosus; less likely if indomethacin given prior to 32

weeks gestation Decreased fetal urine excretion leading to oligohydramnios and, rarely neonatal renal failure Increased incidence of necrotizing enterocolitis, intracranial hemorrhage, and bronchopulmonary dysplasia • Magnesium sulfate – Decreases uterine activity by decreasing intracellular calcium concentrations as well as competitively binding to calcium receptors. – Dose: Loading dose of 4 g IV over 30 minutes; then infusion of 2 g/hr (with normal renal function) to achieve a serum concentration of 5–8 mg/dL (4–7 mEq/L) – Maternal side effects depend on serum magnesium concentration Loss of deep tendon reflexes: 10–12 mg/dL (>7 mEq/L) Respiratory paralysis: 12–18 mg/dL (>10 mEq/L) Cardiac arrest: >25–30 mg/dL (>25 mEq/L) – Fetal side effects: Decreased fetal heart rate variability, hyporeflexia, decreased tone, respiratory depression • Beta-2-adrenergic agonists (terbutaline and ritodrine) – Binding to beta-2-adrenergic receptors within the myometrium activates adenyl cyclase and increases cyclic-AMP. Increased cyclic-AMP decreases intracellular calcium and contractile activity. – Ritodrine dose: Initial dose of 0.05–0.1 mg/minute IV and increased at 15 minute intervals to 0.35 mg/minute – Terbutaline dose: 0.25 mg SQ every 1–6 hours – Maternal side effects: Hypokalemia, hyperglycemia, chest pain, shortness of breath, cardiac arrhythmias, hypotension, pulmonary edema – Fetal side effects: No direct effects • Oxytocin antagonist (atosiban): Currently only available in Europe • Screening for bacterial vaginosis (BV) – BV can increase the risk of preterm birth by two-fold. – Anaerobic organisms replace normal lactobacilli – BV present in up to 25% of pregnant women

PREOPERATIVE ASSESSMENT • Symptoms: – Pelvic pressure – Abdominal cramping – Increase in vaginal discharge – Backache – Painless in up to 50% of instances • Signs/physical examination: – Uterine contractions lasting >30 seconds and occurring at least every 10 minutes – Cervical dilation ≥2 cm – Cervical effacement ≥80%

• Fetal fibronectin (FFN) – A basement membrane protein produced by the fetal membranes and functions as an “adhesion binder” – Appearance of FFN in cervical secretions after 22 weeks may indicate disruption of the normal adhesion between chorioamnion and the underlying decidua – Most useful test when cervical length 16–30 mm – The negative predictive value for preterm delivery (within 7 days of test) is up to 99.5% and 99.2% (within 14 days) • Cervical ultrasonography – Cervical shortening is one of the earliest indicators of cervical incompetency or the onset of labor – Cervical length <25 mm between 16–24 weeks may increase the risk of preterm delivery.

TREATMENT • Increase fetal lung maturity with corticosteroids (betamethasone) (1) – Can decrease the risk of cerebral palsy by up to 45% – Recommended to be administered between 24 and 34 weeks of gestation – Dose: 12 mg IM, repeat in 12–24 hours – The optimum treatment to delivery interval is after 48 hours and within 7 days of steroid use – Contraindications: Chorioamnionitis with sepsis, uncontrolled diabetes mellitus • Fetal neuroprotection with magnesium sulfate (2) – Decreases risk of cerebral palsy up to 45% – Dose: Loading dose of 6 grams IV over 30 minutes, followed by an infusion of 2 grams/hour for a minimum of 12 hours prior to delivery. – Recommended for neonates <32 weeks gestational age • Management of delivery – Cesarean delivery is indicated for breech presentation and low gestational weight (relative). There is some concern that a vaginal delivery may lead to head trauma and subsequent intracranial hemorrhage in neonates with an estimated gestation weight <1,500 grams. A classical or T-incision may be indicated if <32 weeks gestation. Regional anesthesia is preferred over general anesthesia. – Vaginal delivery: The goal is to avoid precipitous delivery that may increase stress on the fetal head. Neuraxial analgesia provides the benefit of a well-relaxed perineum for a controlled delivery. Take into account possible interactions with tocolytic therapy, especially when beta-adrenergic agonists and calcium-channel blockers/antagonists are utilized. • Uterotonic agents following delivery: – At <28 weeks gestation, the uterus may not respond to oxytocin due to insufficient quantity and responsiveness of oxytocin receptors within the myometrium. – Direct-acting uterotonic agents, including methylergonovine and carboprost, may be more effective in achieving adequate uterine tone.

REFERENCES

1. COG Practice bulletin No. 80: Premature rupture of membranes. Obstet Gynecol. 2007;109(4):1007–1019. 2. ACOG Committee opinion no. 455: Magnesium sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol. 2010;115(3):669–671.

ADDITIONAL READING

• Beck S, Wojdyla D, Say L, et al. The worldwide incidence of preterm birth: A systematic review of maternal mortality and morbidity. Bull World Health Organ. 2010;88(1):31–8. • Chandraharan E, Arulkumaran S. Acute tocolysis. Curr Opin Obstet Gynecol. 2005;17(2):151–156. • Hole JW, Tressler TB. Management of preterm labor. J Am Osteopath Assoc. 2001;101:S14– S18. • National Guideline Clearinghouse. Management of preterm labor. • www.acog.org/publications/patient_education/bp087.cfm. The American Congress of Obstetrics and Gynecologists. • www.guidelines.gov/content.aspx?id=3993.

See Also (Topic, Algorithm, Electronic Media Element) • Cerebral palsy • Vaginal delivery • Premature infants

CODES ICD9 644.20 Early onset of delivery, unspecified as to episode of care or not applicable ICD10 O60.00 Preterm labor without delivery, unspecified trimester

CLINICAL PEARLS

• Preterm birth occurs in 12% of pregnancies and is one of the leading causes of neonatal morbidity and mortality. • Tocolytics including magnesium sulfate, calcium channel blockers, prostaglandin synthetase inhibitors, and beta-2-adrenergic agonists can be used to delay preterm delivery. • Corticosteroid administration reduces neonatal morbidity associated with preterm birth. • Magnesium sulfate administration prior to preterm delivery leads to a reduced incidence of cerebral palsy. • Beware of interactions of treatments for preterm labor and anesthetic techniques (e.g., excessive hypotension). • Cesarean delivery is indicated for breech presentation of the preterm neonate.

PROPOFOL INFUSION SYNDROME (PRIS) Jeremy Wong, MD

BASICS DESCRIPTION

• Propofol infusion syndrome (PRIS) was first termed in 1998 to describe a clinical state associated with propofol infusion in children. Patients demonstrated acute refractory bradycardia that led to asystole in the presence of one or more of the following: – Metabolic acidosis (base deficit >10 mmol/L) – Rhabdomyolysis or myoglobinuria – Lipemic plasma – Clinically enlarged or fatty liver on autopsy • A more recent definition of PRIS was published in 2009 and included: – Metabolic acidosis – Cardiac dysfunction – One of the following: Rhabdomyolysis Hypertriglyceridemia Renal failure • To date, most of the information available on PRIS is based on case reports and retrospective studies. EPIDEMIOLOGY Prevalence

• Large prospective study cited an incidence of 1.1% (11 of 1,017 patients) • More than 80 case reports have been recorded. • In a retrospective 2008 MEDWATCH analysis, 1,139 potential cases of PRIS were identified.

Morbidity

Severity ranges from minor laboratory abnormalities that resolve completely without sequelae to multi-organ failure and death Mortality

Reports range from 18–83%

ETIOLOGY/RISK FACTORS

• Large total cumulative propofol dose (>4 mg/kg/hr for longer than 48 hours) • Severe head injury • Airway infection • High catecholamine and serum glucocorticoid levels • Low carbohydrate intake/high fat intake

• Critical illness • Young age • Inborn errors of fatty acid oxidation

PHYSIOLOGY/PATHOPHYSIOLOGY

• Propofol is commonly used in the perioperative period for its sedative and hypnotic properties. It can be utilized to induce and maintain general anesthesia (solely or in combination with other agents) as well as for sedation during procedures, to reduce intracranial pressure, provide neuroprotection, or to maintain sedation with mechanical ventilation. – Mechanism of action: Potentiates GABA receptor binding by attaching to the beta subunit of the GABAA receptor. GABA is an inhibitory neurotransmitter that hyperpolarizes the

cell membrane (increases chloride conductance), thereby preventing depolarization and neurotransmission. – Cardiovascular effects: Capable of profound decreases in systolic BP from vasodilation of the arterial and venous systems, as well as myocardial depression and bradycardia. Propofol’s antagonist effect at beta-receptors and calcium channels is believed to result in bradycardia and impaired myocardial contractility. – Onset: 90–100 seconds or “one arm–brain circulation” – Metabolism: Hepatic and extra-hepatic metabolism. The liver metabolizes propofol to inactive water-soluble compounds (glucuronide, sulfate) that are renally excreted. The lungs and kidneys are responsible for 30–60% of elimination; the urine and feces 3%. • The pathophysiology of PRIS is complex, involving multiple simultaneous mechanisms but has the common feature of cardiovascular collapse • Impairment of ATP production: Propofol inhibits beta-oxidation of free fatty acids and the mitochondrial electron transport chain. This results in a disruption of ATP production, cellular hypoxia, and metabolic acidosis. The imbalance between cellular energy production and utilization causes peripheral and cardiac muscle necrosis. • Arrhythmias: Damage to the myocardial conduction system of the heart may result from: – Direct effects of propofol on ion currents – Indirect effects by increased free fatty acid levels, acidosis, and hyperkalemia • Risk factors – High levels of endogenous and exogenous catecholamines increase the cardiac output and portal flow. This can increase propofol requirements and the potential for PRIS with myofibrillar degeneration and stress cardiomyopathy. – Mitochondrial myopathies result from defects in the mitochondrial respiratory chain. When they are stressed with illness, infection, or starvation, they are unable to utilize free-fatty acids for energy. This results in muscle cell breakdown and can be compounded with propofol administration.

PREVENTATIVE MEASURES

In the critically ill, consider maintaining an adequate carbohydrate supply, limiting excess lipid loads, or using alternative methods of sedation. • Patients with inadequate carbohydrate intake or children (with smaller carbohydrate stores)

may tend towards fat metabolism and thus increased circulating fatty-acid load, which may predispose to PRIS. • Evidence is mixed regarding the contribution of lipid load to PRIS. It is unclear whether or not the lipid component of propofol is at least partly responsible for the development of PRIS.

PREOPERATIVE ASSESSMENT • Although no specific test is available, monitoring of pH, lactate, and CK levels are recommended when unusually high doses or long infusion periods are unavoidable, or in high-risk patients. It should be noted, however, that there have been reports of PRIS deaths despite frequent laboratory monitoring and immediate cessation of propofol upon the development of laboratory abnormalities. • Presentation varies considerably, but practitioners should be aware of the signs that have been described. – Early signs can include unexplained lactic acidosis, lipemic serum, and cardiac dysfunction or Brugada-like electrocardiogram changes. – Later signs include cardiac failure, tachyarrhythmias or heart block, ventricular fibrillation or ventricular tachycardia, rhabdomyolysis (elevated CPK and myoglobinuria), hyperkalemia, renal failure, and fatty degeneration of the liver.

DIFFERENTIAL DIAGNOSIS

Consider other causes of lactic acidosis:

• Decreased oxygen delivery – Hypotension (hypovolemia, cardiogenic shock, septic shock) – Severe anemia – Severe hypoxemia – Carbon monoxide poisoning – Ischemic tissue (bowel, extremity, etc.) • Increased oxygen demand – Exercise – Seizures – Shivering – Malignant hyperthermia • Disrupted oxygen utilization – SIRS – Malignancy – TPN (with thiamine deficiency) – Congenital lactic acidosis – Mitochondrial myopathies – Drugs/toxins (NRTIs, metformin, nitroprusside, alcohol, propylene glycol, salicylates)

TREATMENT

• PRIS is difficult to treat once it develops; efforts are mostly supportive. • Discontinue propofol immediately. • Cardiorespiratory support should be provided as needed. • Hemodialysis/hemofiltration has been reported to be effective. • Partial exchange blood transfusion (PEBT) has been recently reported in the treatment of PRIS. A hemodynamically unstable 10-year-old boy on propofol for the treatment of status epilepticus was successfully treated with PEBT as a bridge to continuous veno-venous hemofiltration. • IV fluids and inotropes are often ineffective. • Cardiac pacing has shown some success in several case reports. • ECMO has been reported in the successful treatment of 3 patients with PRIS. In a recently published case report, a 17-year-old on propofol for status epilepticus developed PRIS. Lactic acidosis improved with continuous hemofiltration, but cardiovascular collapse developed. ECMO was successfully used until cardiac recovery ensued and was discontinued 5 days later.

REFERENCES

1. am PCA, Cardone D. Propofol infusion syndrome. Anaesthesia. 2007;62:690–701. 2. asile B, Rasulo F, Candiani A, et al. The pathophysiology of propofol infusion syndrome: A simple name for a complex syndrome. Intensive Care Med. 2003;29:1417–1425. 3. Wysowski D, et al.Reports of death with use of propofol (Diprivan) for nonprocedural (long-term) sedation and literature review. Anesthesiology. 2006;105(5):1047–1051. 4. Roberts R, et al.Incidence of propofol-related infusion syndrome in critically ill adults: A prospective, multicenter study. Crit Care. 2009;13:R169.

ADDITIONAL READING

• Da-Silva SS, Wong R, Coquillon P, Gavrilita C, Asuncion A. Partial-exchange blood transfusion: An effective method for preventing mortality in a child with propofol infusion syndrome.Pediatrics.2010;125(6):e1493–e1499.Guitton J, et al.Propofol infusion syndrome during refractory status epilepticus in a young adult: Successful ECMO resuscitation. Neurocrit Care. 2010.

See Also (Topic, Algorithm, Electronic Media Element) Lactic acidosis

CODES ICD9 995.22 Unspecified adverse effect of anesthesia ICD10 T88.59XA Other complications of anesthesia, initial encounter

CLINICAL PEARLS

• The infusion rate and duration of infusion are particularly important risk factors for the development of PRIS. It is recommended that infusions >4 mg/kg/hr for longer than 48 hours be avoided. • Early PRIS, however, has been shown to develop during high-dose, short-term infusions such as those used in the practice of anesthesiology. • Special care should be taken when patients receive high-dose infusions or prolonged infusions, and in those who have risk factors that make the development of PRIS more likely (such as mitochondrial disease or fatty acid oxidation defects, young age, critical illness of the CNS or respiratory origin, exogenous catecholamine or glucocorticoid administration, or inadequate carbohydrate intake). • The monitoring of pH, lactate, and CK is recommended when unusually high doses or long infusion periods are unavoidable. • If prolonged or high-dose propofol administration is unavoidable, supplemental sedatives can be used to decrease the amount of propofol necessary for the desired level of sedation. Note, however, that a recent study in rabbits suggests that using an adjunct-like remifentanil did not delay or prevent the development of PRIS despite reducing the tolerance to co-administered propofol.

PROSTATECTOMY Matthew D. Cohen, DO

BASICS DESCRIPTION General

• Prostatectomies are performed: – Either to reduce the size of the prostate when causing bladder outlet obstruction, or to remove the prostate secondary to tumor. – Via open, laparoscopic, robotic assisted (RALRP), or trans-urethral (TURP) approaches. • TURP is used for the treatment of bladder outlet obstruction from enlargement of the prostate, but is not a treatment for prostate cancer. It is performed through a specialized cystoscope (resectoscope) through which an electrocautery loop is passed and used to reduce the impingement of the urethra caused by the prostate. Newer techniques use a laser (PVP, greenlight) to vaporize the portion of the prostate that is causing obstruction. This is associated with a nearly bloodless surgical field. • Open procedures, radical perineal prostatectomy (RPP), or radical retropubic prostatectomy (RRP) allow direct visualization and access. They are generally used for larger tumors or significant intraperitoneal metastatic disease and are associated with increased blood loss, and possibly longer hospital length of stay. However, this is largely dependent on an individual surgeon’s practice and other patient factors. Some studies show a more favorable oncologic outcome and improved urinary continence rates for open procedures but others refute that finding (4). • Robotic or laparoscopic techniques are generally used for patients with limited disease; robotic procedures allow for increased dexterity. The data is conflicting with regards to complication rate and oncologic outcomes compared to open procedures. There does seem to be a higher rate of bowel injuries and fistula formation though, with a minimally invasive approach (4).

Position

• TURP: Lithotomy, arms out • Open abdominal: Supine, arms out • Open RPP: Lithotomy, arms out • Laparoscopic/RALRP: Lithotomy, arms tucked, steep Trendelenburg (up to 40°) (1).

Incision

• TURP: None, equipment inserted via penis • Abdominal: Low midline or Pfannenstiel • RRP: Perineal • Laparoscopic/RARLP: 4–5 small incisions for trochar insertion

Approximate Time

• Surgical time will vary by institution and surgeon skill • TURP: 1–2 hours; longer duration is associated with higher risk of TURP syndrome • Open: 1–3 hours • RPP: 3 hours • RALRP: 2–4 hours

EBL Expected

• TURP: <500 mL • Open simple: 500 mL • RRP 200 mL–1500 mL (3) • Robotic: 50–1,000 mL (3). • Some patients with prostate cancer have a mild DIC that manifests perioperatively and can result in higher than expected blood loss

Hospital Stay

• The majority of patients are discharged on the first postoperative day. • TURP patients are often kept overnight to monitor for any significant postoperative bleeding. • Open procedures: 1–3 days

Special Equipment for Surgery

• TURP procedures require cystoscopy equipment and a fluid irrigation system • For laser vaporization of the prostate, everyone in the OR, including the patient, must wear protective eyewear to reduce the chance of injury if the laser fiber should break, causing exposure to laser light. • da Vinci® robotic surgical system for RARLP

EPIDEMIOLOGY Prevalence

Benign prostatic hyperplasia will occur in >80% of men; surgical intervention is required in ∼20%. Prevalence

There were approximately 2,276,112 men alive in the US with a diagnosis of cancer as of January 1, 2007. Morbidity

• Surgical complications include bleeding, infection, incontinence, impotence • TURP: Significant intraoperative bleeding (10%), failure to void (6.5%), TURP syndrome (2– 5%), perforation of the bladder/urethra (<0.5%) • Robotic/laparoscopic: Postoperative vision loss (ischemic optic neuropathy) is a rare but devastating complication that may be influenced by prolonged surgical times in a steep head-down position, hypotension, and pronounced hemodilution.

Mortality

Thirty-day mortality for TURP and open procedures is <1%. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Although TURP and RALRP are minimally invasive procedures, the patients are often elderly and have significant comorbidities that must be considered. • The anaesthetist must be vigilant for signs of venous gas embolism during dissection of the deep dorsal venous plexus. • Appropriate fluid management during RALRP can positively impact outcomes. Minimizing fluids given prior to dissection of the deep dorsal venous plexus and removal of the prostate results in significantly decreased blood loss throughout the procedure (7).

PREOPERATIVE ASSESSMENT SYMPTOMS

• BPH: Difficult urination, weak urinary stream, and waking at night to void. • Advanced or metastatic disease: Bone pain, anemia, and renal failure.

History

• Inquire about common comorbidities such as COPD, CAD, and urinary retention/renal failure. • Patients with glaucoma, history of CVA, or cerebral aneurysm may be poor candidates for robotic or laparoscopic procedures requiring steep Trendelenburg positioning.

Signs/Physical Exam

• A thorough physical examination including auscultation of heart and lungs and evaluation of peripheral pulses should be performed. • A standard airway examination. • A neurologic examination can help identify pre-existing nerve injuries.

MEDICATIONS

• Chemotherapeutic agents • Alpha-adrenergic antagonists

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Preoperative Hgb/Hct along with Type and Screen is appropriate for all radical prostatectomies. Cross-matching of blood products should be considered on the basis of patient factors and surgeon skill/expected blood loss. • Coagulation studies and platelet count should be considered prior to a planned neuraxial anesthetic, particularly if the clinical history suggests. • Other tests (e.g., ECG, Echo, PFT) are based on comorbid conditions.

CONCOMITANT ORGAN DYSFUNCTION

• Renal failure and azotemia can result from prolonged, severe, untreated prostatic hypertrophy, and urinary obstruction. • Metastatic disease to the brain, spine, or abdominal organs is possible.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Caution should be exercised when using benzodiazepines in elderly patients as their effects can be prolonged. • Continue perioperative beta-blockade

Special Concerns for Informed Consent

• For RALRP, a discussion of the positioning and the risk of facial swelling, nerve palsies, postoperative vision loss, and possible need for postoperative intubation (due to airway edema) should occur. • For neuraxial techniques, either as the sole anesthetic in TURP or for postoperative pain management in open procedures, a discussion of the risks and benefits should be conducted. Antibiotics/Common Organisms

• Antibiotic prophylaxis has been shown to reduce postoperative bacteriuria, bacteremia, high-grade fever, and use of additional perioperative antibiotics (2). • TURP – Fluoroquinolone or TMP–SMX is the preferred antibiotic. – Alternatively may use aminoglycoside +/− ampicillin or a first/second generation cephalosporin. • Open or laparoscopic – First/second generation cephalosporin, aminoglycoside + clindamycin, or flagyl preferred. – Alternatively may use fluoroquinolone or ampicillin/sulbactam. INTRAOPERATIVE CARE Choice of Anesthesia

• Open procedures: GETA +/− epidural – Epidural analgesia may reduce the risk of postoperative DVT and ileus. There is some weak evidence that with lower grade tumors, epidural analgesia is associated with improved oncologic outcomes (6). • TURP: General anesthesia (GA) or neuraxial (need T10 level). Considerations include: – Allows for continuous monitoring of the patient’s mental status for signs of TURP syndrome or fluid overload. – Does not block the obturator reflex. The obturator nerve originates from L2–4 and runs close to the prostatic urethra, bladder neck, and inferolateral bladder wall. Bladder distention from irrigating fluid brings the nerve close to the lateral bladder wall; thus,

electrical currents can stimulate the nerve and cause an adductor muscle reflex of the lower extremity. An obturator nerve block by the surgeon can prevent this (needs to be blocked before it bifurcates into the anterior and posterior divisions). • Laparoscopic/Robotic: General endotracheal anesthesia

Monitors

• Standard ASA monitors • Two large bore IVs for radical prostatectomy • Urine output is often interrupted during the procedure and is unreliable as a monitor. Hematuria is not unexpected. • Arterial lines are sometimes used during robotic procedures because access to the patient is severely limited when the robot is engaged.

Induction/Airway Management

Standard induction and airway management with alteration, as needed, depending on patient comorbidities or physical examination (e.g., difficult airway). Maintenance

• Any standard balanced maintenance technique is appropriate. • During TURP, ensure an adequate depth of anesthesia to prevent movement that may cause injury to the external urinary sphincter and lead to postoperative incontinence. Note: GA without muscle relaxation does not prevent the obturator reflex from occurring. Fluids should be judiciously administered, as absorption from the open prostatic venous plexuses can result in hypervolemia. • Muscle relaxation during a RALRP is critically important; patient movement while the robot is engaged can lead to significant injury to the patient and damage to the equipment.

Extubation/Emergence

RALRP is associated with upper airway edema and an endotracheal tube occlusion test is often performed prior to extubation to ensure airway patency.

FOLLOW-UP BED ACUITY

Medical–Surgical unit, unless comorbid conditions warrant more advanced cardiac monitoring. ANALGESIA

• For open procedures, a combination of IV, oral and/or peridural analgesics are often used. • For minimally invasive techniques, IV or oral analgesics are often sufficient.

COMPLICATIONS

• Postoperative erectile dysfunction: Regardless of technique, preservation of the neurovascular bundles is critical in preserving potency. • Obturator or peroneal nerve injury from lithotomy positioning

• Rectal injury – Delayed bleeding • Urinary incontinence is common initially but over 90% eventually regain good urinary control. • TURP – Complications related to irrigant absorption (TURP syndrome, hypothermia, CHF, DIC, blindness) – Bacteremia/sepsis – Bladder rupture

PROGNOSIS

• For BPH, prognosis is good once obstruction is removed. • For organ-contained malignancies, the 10-year survival is 70–85% after prostatectomy. If there is extracapsular extension of disease, the survival rate is 60% at 5 years and 30% at 10 years.

REFERENCES

1. Kalmar AF, et al. Influence of steep Trendelenburg position and CO(2) pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during robotic prostatectomy. Br J Anaesth. 2010;104(4):433–439. 2. Wolf JS, et al. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol. 2008;179(4):1379–1390. 3. Farnham SB, et al. Intraoperative blood loss and transfusion requirements for roboticassisted radical prostatectomy versus radical retropubic prostatectomy. Urology. 2006;67(2):360–363. 4. Nelson JB. Debate: Open radical prostatectomy vs laparoscopic vs robotic. Urol Oncol. 2007;25(6):490–493. 5. Sanda MG. Genetic susceptibility of benign prostatic hyperplasia. J Urol. 1994;152(1):115– 119. 6. Umbreit E, et al. Percutaneous nephrolithotomy for large or multiple upper tract calculi and autosomal dominant polycystic kidney disease. J Urol. 2010;183(1):183–187. See Also (Topic, Algorithm, Electronic Media Element) • TURP syndrome • Laparoscopy

CLINICAL PEARLS

• Patients presenting for prostatectomy are often elderly with multiple comorbid conditions. • Acute septicemia may occur in up to 6–7% of patients undergoing TURP. This may manifest as tachycardia, fever, and chills, however, severe cases may result in “septic shock” with cardiovascular collapse. • Patients undergoing RALRP should be gradually placed into the steep Trendelenburg

position to ensure adequate ventilation, hemodynamic stability, and stability of patient position.

PROTEIN C

John B. Carter, MD

BASICS DESCRIPTION

• Protein C has 2 functions: – As an anticoagulant within the coagulation cascade – Modulates the inflammatory response • Homozygous Protein C deficiency is a rare, fatal thrombotic disease. Heterozygous disease occurs more commonly and increases the risk of venous thromboembolism. • Acquired deficiencies in Protein C can also be seen in sepsis, and its levels can serve as a predictor of mortality. PHYSIOLOGY PRINCIPLES

• Protein C is a vitamin-K anticoagulant that is synthesized by the liver in an inactive form (1). • Anticoagulant functions – Conversion of Protein C to activated protein C (aPC) by thrombin occurs on the endothelial cell surface and involves 2 membrane receptors: Thrombomodulin, endothelial protein C receptor (1,2). – Thrombomodulin – Endothelial Protein C receptor. – The major action of aPC is to inactivate factors Va and VIIIa, as well as neutralize plasminogen activator inhibitor; its overall effect is reduction of blood clotting. Additionally, its actions are enhanced by protein S (1,2). – These antithrombotic actions are especially important to the venous circulation as well as the microcirculation. • Anti-inflammatory and cytoprotective functions (3) – Mediated through endothelial Protein C receptor and protease-activated receptor-1 – Inflammatory mediators are also down-regulated

PHYSIOLOGY/PATHOPHYSIOLOGY

• Hereditary deficiency is an autosomal dominant disorder. Heterozygous presentation has an incidence of 1 in 200 to 1 in 500 in the population; it is higher in those with a history of thromboembolism. Mutations can result in either quantitative or qualitative deficiencies (2). – Type 1: Quantitative defect of Protein C (most common). This can result from a decrease in production or half-life of Protein C. – Type 2: Qualitative defect of Protein C, with normal levels. This can result from defects in its interaction with thrombomodulins, factor V, and factor VIII. – Venous thrombosis Typically present after adolescence

Great deal of phenotypical variation In heterozygotes, it most commonly occurs spontaneously (70%) but can also result during pregnancy or in the postoperative arena (30%). Has an increased incidence when associated with another deficiency such as protein S, antithrombin III, or factor V Leiden. Acute events are treated with heparin; long-term anticoagulation with warfarin or low molecular weight heparin (LMWH) is frequently indicated. Warfarin-induced skin necrosis. Because warfarin’s mechanism of action is via suppression of vitamin K epoxide reductase, it not only decreases synthesis of coagulant factors, but also Protein C. Additionally, Protein C levels are decreased prior to other coagulant factors, thus causing a transient hypercoagulable state Hematology consultation is necessary for management Arterial thrombosis is not increased Homozygous or double heterozygous fatality commonly occurs in infancy from neonatal purpura fulminans. Administration of Protein C concentrate (Ceprotin; derived from fresh frozen plasma) may be useful. • Acquired protein C deficiency can result from: – Disseminated intravascular coagulopathy (DIC) – Severe liver disease – Hemolytic uremic syndrome – Thrombotic thrombocytopenic purpura – Sepsis (4,5): Critically ill patients often have systemic activation of both inflammation and coagulation Pro-inflammatory cytokines have been shown to impair anticoagulant pathways such as the Protein C system. Coagulation can also affect inflammatory activity. Activated coagulation proteases have been shown to affect specific cellular receptors on inflammatory and endothelial cells, thereby modulating the inflammatory response (1). This relationship appears to play a major role in microvascular failure and subsequent organ failure (1). Recombinant human aPC (drotrecogin alfa) and Xigris (Eli Lilly) have antithrombotic, prothrombolytic, and anti-inflammatory effects. They have been FDA-approved in the treatment of sepsis.

PERIOPERATIVE RELEVANCE

• Patients with Protein C deficiency are at increased risk of thrombosis and long-term anticoagulation is frequently advised during pregnancy or after a deep venous thrombosis. Perioperative anticoagulation management should be discussed and coordinated with the surgeon and hematologist. – Consider “bridging” with LMWH. – Heparin SQ should be considered. – Sequential compression devices should be started. – In addition, anticoagulation should be re-instituted as soon as feasible. • Regional anesthesia and anticoagulation – See ASRA guidelines for specific recommendations.

– Neuraxial blocks: If the benefit (pain control, increased lower extremity blood flow, reduced intraoperative bleeding, etc) is significant, then placement and catheter removal should be considered and coordinated around anticoagulation issues. – Peripheral nerve blocks: In general, anatomical landmarks are well defined or easily visualized with ultrasound imaging and a developing hematoma can be easily accessed and compressed. On the other hand, if infraclavicular brachial plexus blocks or deeper blocks such as the posterior lumbar plexus block (especially with the use of continuous catheter technique) are performed, bleeding complications may not be easily diagnosed or treated. • In the ICU, decreased Protein C levels have been associated with increased mortality, multisystem organ failure, and/or sepsis.

REFERENCES

1. Levi M, van der Poll T. Inflammation and Coagulation. Crit Care Med. 2010;38(2 Suppl):S26–34.

2. Bick Rodger. Prothrombin G20210A mutation, antithrombin, heparin cofactor II, protein C, and protein S defects. Hemotol Oncol Clin N Am. 2003;17:9–36. 3. Mosnier LO, Zlokovic BV, Griffin JH. The cytoprotective protein C pathway. Blood. 2007;109:3161–3172. 4. Brunkhorst F, Sakr Y, Hagel S, et al. Protein C concentrations correlate with organ dysfunction and predict outcome independent of the presence of sepsis. Anesthesiology. 2007;107:15–23. 5. Marti-Carvajal A, Salanti G, Cardona AF. Human recombinant activated protein C for severe sepsis. The Cochrane Database of Systematic Reviews. 2007;3:CD 004388. 6. Bernhard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. Massachusetts Medical Society. 2001. See Also (Topic, Algorithm, Electronic Media Element)

• Sepsis • Pulmonary embolism • Prothrombin time • Epidural hematoma

CLINICAL PEARLS

• Heterozygous Protein C deficiency is a relatively common disorder associated with an increased incidence of thromboembolism. It may be considered if there is a family history of venous thrombosis. The diagnosis and management are best performed by a hematologist. • While mortality in sepsis is associated with decreased levels of Protein C, recombinant aPC is not routinely prescribed. In the PROWESS trial, the 28-day survival was improved by 6.1%; however, there was an increased risk of bleeding. Other trials have not supported these findings. There is weak evidence to support its use in patients with severe sepsis (APACHE score > 25) and at a high risk of death. At this time, more randomized controlled

trials are needed. In addition, a Cochrane review in 2007 concluded that recombinant aPC is not indicated in pediatrics (4,6).

PROTHROMBIN TIME (PT) Parisa Partownavid, MD

BASICS DESCRIPTION

• The PT is a screening test for hemostasis, and is one of the most frequently ordered tests in coagulation medicine. • It is a measure of the integrity of the extrinsic and final common pathways of the procoagulant cascade (Figure 1).

FIGURE 1. Schematic of coagulation cascade. HMWK = high-molecular-weight kininogen; PK = prekallikrein.

• PT represents the time (in seconds), for the patient’s plasma to clot after the addition of calcium and an activator (tissue factor/factor III) of the extrinsic pathway

PHYSIOLOGY PRINCIPLES

• The PT measures coagulation factors in the extrinsic and common pathways. These factors (in order of their role in the coagulation cascade) are: – Factor VII (extrinsic pathway) – Factor V (common pathway) – Factor X (common pathway) – Factor II (common pathway) – Fibrinogen (common pathway) • The liver synthesizes Factor V and fibrinogen. Factors II, VII, and X are Vitamin-K-dependent factors that are also synthesized in the liver. • The normal range: Depends on the reagent and instrument combinations that each laboratory uses. To that extent, the International Normalized Ratio (INR) is utilized to standardize PT results. The tissue factor (TF) manufacturer provides an International Sensitivity Index (ISI) that is derived from an international TF reference and utilized to

calculate INR values.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Deficiencies or inhibitors of clotting factors within the extrinsic and final common pathways result in prolongation of the PT. Etiologies can result from systemic disease, vitamin K antagonists or deficiencies, congenital deficiencies, inhibitors, and artificial causes. • Systemic disease: – Liver disease: All coagulation factors are made in the liver except for vWF and a subunit of factor XIII – Connective tissue disease: Produces lupus anticoagulants – Amyloidosis: Results in factor X deficiency – Myeloproliferative disease: Results in factor V deficiency – Disseminated intravascular coagulation and fibrinolysis • Anticoagulation – Warfarin inhibits vitamin K epoxide reductase which is responsible for the synthesis of Factors II, VII, IX, and X (common, extrinsic, and intrinsic pathways). PT is the most sensitive measure of factor VII and X activity. – Heparin binds to antithrombin III, causing a conformational change that accelerates its action 1000–3000-fold. Activated antithrombin III inactivates thrombin and Factor X (common pathway). PTT is a more sensitive measure of heparin’s effects. • Vitamin K deficiencies: – Decreased nutritional intake – Malabsorption • Congenital coagulation factor deficiency: – Factor II, V, VII, or X (autosomal inheritance) • Presence of an inhibitor – Specific factor inhibitors directed against specific clotting factors, (e.g., factor VIII or factor V inhibitors). – Nonspecific inhibitors (e.g., lupus anticoagulants) • Artificial causes: – Lipemic, icteric, or hemolyzed plasma samples (interferes with light transmission). – High hematocrit (Hct) in patients with erythrocytosis (more plasma to anticoagulant ratio). – Even in the absence of the above conditions, the test needs to be repeated.

PERIOPERATIVE RELEVANCE

• In general anesthesia with an abnormal PT, consider avoiding: – Nasal airway/intubation – Esophageal and gastric instrumentation – Central line placement in the thorax or neck. Adequate compression in the thorax is difficult, but can be performed in the neck. If placement in the neck is attempted, ultrasound may reduce inadvertent carotid artery puncture. • In neuraxial anesthetic techniques, a prolonged PT can increase the risk of bleeding around the spinal cord. – Epidural hematoma is considered the most significant hemorrhagic complication in

regional anesthesia due to the catastrophic nature of bleeding into a fixed and noncompressible space. – Incidence: Actual incidence of neurologic dysfunction from hemorrhagic complications associated with neuraxial blockade is unknown. Although the incidence cited in the literature is estimated to be <1 in 150,000 epidural anesthetics, and <1 in 220,000 spinal anesthetics, recent epidemiologic surveys suggest that the frequency is increasing and may be as high as 1 in 3,000 in some patient populations. – Management: The decision to perform spinal or epidural anesthesia/analgesia and the timing of catheter removal in a patient receiving antithrombotic therapy should be made on an individual basis. The risk of a spinal hematoma must be weighed against the benefits of regional anesthesia for a specific patient. If spinal or epidural needle/catheter placement is performed, the patient’s coagulation status should be optimized during placement, duration of epidural catheterization, and removal of the catheter. • In plexus and peripheral nerve blockade, the associated risk of bleeding remains undefined. – Neurologic deficits: The expandable nature of the peripheral site decreases the chance of irreversible neural ischemia (unlike the epidural space). – Massive hemorrhage: Bleeding into the neurovascular sheath (especially in plexus blocks) may result in a significant decrease in the hematocrit. – Incidence: Due to the rarity of the complications and lack of randomized studies, the information available is based on case reports. The overall incidence of bleeding complications associated with peripheral nerve blocks is low. – Management: The decision to perform peripheral nerve or plexus block (single injection or continuous catheter infusion) would be at the discretion of the anaesthetist weighing the benefit of regional anesthesia against the risk of neural damage from hematoma or bleeding complications. Generally, in superficial limb blocks, anatomical landmarks are well defined or easily visualized with ultrasound imaging and a developing hematoma is easily accessed and compressed. In deeper blocks (e.g., posterior lumbar plexus block, infraclavicular brachial plexus block), bleeding complications may not be easily diagnosed, especially with the use of continuous catheter technique. • Warfarin therapy – During the first few days of therapy, the PT reflects primarily a reduction of factor VII, the half-life of which is ∼6 hours. – After discontinuation of warfarin therapy, the coagulation status may not be adequate in the first 1–3 days for hemostasis in spite of a decrease in the PT or the INR (indicating return of factor VII activity). – Warfarin therapy should have been stopped for 4–5 days before initiation of neuraxial block in addition to normalization of the PT/INR. – In urgent/emergent situations, the effects of warfarin may be reversed by oral or intravenous of vitamin K and/or transfusion of fresh frozen plasma.

GRAPHS/FIGURES

FIGURE 2. Approach to a prolonged PT.

REFERENCES

1. amal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007;82(7):864–873. 2. uilenburg DJ, Singh A, Torzilli G, et al. Surgery in the patient with liver disease. Anesthesiol Clin. 2009;27(4):721–737 3. orlocker TT, Wedel DJ, Rolingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy. American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines 3rd ed. Reg Anesth Pain Med. 2010;35(1):64–101. 4. Ho M, Ganapathy S. Is peripheral/plexus block safe in the anticoagulated patient? Techniques in Regional Anesthesia and Pain Management. 2006;10:56–61. See Also (Topic, Algorithm, Electronic Media Element) • Epidural hematoma • Partial thromboplastin time • Cirrhosis

CLINICAL PEARLS

• There are no practice advisories or guidelines regarding routine coagulation testing. It is generally performed when clinical or medication history suggests the potential for a coagulopathy.

• It is important to recognize bleeding disorders that will not be detected by PT assays. These disorders include: – Qualitative and quantitative platelet defects, which require specialized platelet function testing. – von Willebrand disease, which requires assays for the von Willebrand factor – Factor XIII deficiency, which requires specialized factor XIII screening or functional assays. – Deficiency of plasminogen activator inhibitor 1, which requires specific assays.

PULMONARY ARTERY CATHETER WAVEFORMS Lauren Mai Pieczynski, MD Adam Thaler, DO

BASICS DESCRIPTION

• Pulmonary artery catheters are flow-directed, balloon-tipped devices that can provide: – Pressure measurements of the central venous/right atrium (RA), right ventricle (RV), and pulmonary artery (PA); the left atrial and left ventricular end diastolic pressure can be estimated by the pulmonary capillary wedge pressure (PCWP), also known as the PA occlusion or wedge pressure. – An assessment of the cardiac output/cardiac index – Values to calculate the pulmonary vascular resistance (PVR) and the systemic vascular resistance (SVR). – Sampling of blood from the RA, RV, and PA; mixed venous oxygen saturation can be determined. • Pressure values are a surrogate for volume, and are dependent upon the chamber compliance. To that extent, the use of echocardiography can provide a direct assessment of volume. • Several randomized clinical trials have not been able to convincingly demonstrate the benefits of intervention on patient outcome in terms of morbidity and mortality in the ICU, management of heart failure, or the perioperative period PHYSIOLOGY PRINCIPLES

• RA waveform: Consists of 3 positive (a, c, v waves) and 2 negative (x, y descents) deflections. – a wave reflects RA contraction near the end of ventricular diastole. – c wave reflects bulging of the tricuspid valve into the RA during early ventricular systole. – x descent corresponds to atrial relaxation and decreased RA pressure. – v wave represents passive atrial filling during ventricular systole. – y descent corresponds to tricuspid valve opening and filling of the RV in early ventricular diastole. – The numeric value represents the mean pressure and is a surrogate for preload. • RV waveform: – Systolic pressure is dramatically increased, with a prominent upstroke and downstroke. – Diastole is characterized by a flattened upstroke as the RV rapidly fills with blood; this is followed by a slow filling phase and then atrial systole (steeper slope). – The numeric value is displayed as a systolic and diastolic value. • PA waveform: – Systolic pressure is similar to the RV pressure, but the diastolic pressure is increased (represents the diastolic vascular tone).

– A dicrotic notch represents closure of the pulmonic valve. • PCWP waveform: – Reflects LA pressures, with a shape similar to the RA tracing, but with higher pressure values and a more irregular tracing. – a wave reflects LA contraction. – c wave is often not seen, but reflects the mitral valve closure. – x descent represents the decrease in LA pressure following the a wave. – v wave represents the LA filling. – y descent corresponds with decreased LA pressure following opening of the mitral valve and filling of the LV. – Numeric values are used to estimate the LV end diastolic pressure (LVEDP; surrogate for LV preload) if no obstruction exists between the LA and the LV • Respiratory cycle: Should be considered when interpreting pressure measurements. – During spontaneous inspiration, the intrathoracic pressure decreases; whereas with exhalation, it increases. In the intubated patient, positive pressure ventilation has the reverse effect. – Therefore, in order to minimize respiratory effects, measurements are made at endexpiration, when the intrathoracic pressure is close to zero.

ANATOMY

• The standard, adult PAC is 7.0–9.0 FR and ∼110 cm in length. It has several lumens and connections for transducing pressures. The lumens from proximal to distal are: Proximal lumen (25 cm from the distal tip, lies in the RA); injectate lumen (∼20 cm from the distal tip, lies in the RV); thermistor lumen (∼4 cm from the distal tip); distal lumen (tip of catheter, lies in either the right or left side of the PA); balloon lumen (tip of catheter, can inject 1.5 mL of air). • Following the placement of a sterile introducer sheath into a central vein, the PA catheter is inserted while monitoring the waveforms and pressures. After the catheter tip has entered the RV, the distal balloon is inflated to “float” the catheter as blood is pumped toward the LV; akin to a sail amongst waves. Proper positioning is determined by the pressure waveform or fluoroscopic guidance.

PHYSIOLOGY/PATHOPHYSIOLOGY

• RA pressure reflects the central venous pressure (CVP), and is increased in RV failure, rightsided valvular disease, and cardiac tamponade. – Enlarged a waves are seen with tricuspid stenosis. “Cannon" a waves are seen with atrioventricular dissociation (RA contracts against a closed tricuspid valve during ventricular contraction). – a waves may be absent in atrial fibrillation. – Enlarged v waves are present with tricuspid regurgitation. – Tamponade impairs venous return, decreasing the end-diastolic volume and cardiac output, dramatically increasing filling pressures, and leading to the equalization of pressures in all chambers at end-diastole. • RV systolic pressure is increased in pulmonary hypertension, pulmonic stenosis, or pulmonary embolism. RV diastolic pressure is increased in right heart failure and cardiac

tamponade. • PA pressure elevations are seen in left heart failure, mitral valve disease, and primary parenchymal lung diseases such as chronic bronchitis and emphysema. Pulmonary vascular disease from pulmonary embolism and primary pulmonary hypertension also lead to elevated pressures. Left-to-right cardiac shunts, as in atrial septal and ventricular septal defects, are other potential causes. • PCWP can be increased in left heart failure and mitral valvular disease. – Enlarged a waves can be seen during mitral stenosis. – Elevated v waves can be present with mitral regurgitation or ventricular septal defects. • Complications with placement of the PAC. – Arrhythmias are the most common complication Transient PVCs: 68% of placements Transient right bundle branch block: 5%. In patients with pre-existing left bundle branch block, it can lead to a complete heart block Persistent ventricular dysrhythmias: 3.1% Atrial dysrhythmias: 1.3% – Pneumothorax occurs with 0.5% of IJ cannulations, but is more common with subclavian vein catheter placement. – Infections can occur, with increased frequency in continuous monitoring and in patients with pre-existing sepsis. – Hemorrhage and damage to vascular structures can also occur. PA rupture is rare, occurring in 0.02–0.2%, but has a mortality rate of 50%.

PERIOPERATIVE RELEVANCE

• Despite the widespread use of PA catheters in hemodynamically unstable patients, there are many controversies that exist regarding appropriate indications for their usage. The American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization concluded that the placement of PA catheters should not be routinely used with low risk of hemodynamic complications, and should be reserved for high-risk settings that depend on the patient, surgery, and practice-setting variables. If clinical assessment or non-invasive measures are not appropriate to determine the hemodynamic status, or if the use of the catheter can change management, then its use is indicated. – Indications for PAC in surgical patients include: – Procedures that have a high-risk of complications from hemodynamic shifts (cardiac surgery, aortic cross-clamping, liver transplantation). – Patients with advanced cardiopulmonary disease. – Shock. Can aid in the diagnosis, management, and measurement of therapeutic responses. – Pulmonary edema to differentiate between the mechanisms (cardiogenic versus noncardiogenic).

EQUATIONS

• Normal pressure values – RA: 1–5 mm Hg (mean) – RV: 15–30/1–7 mm Hg – PA: 15–30/4–12 mm Hg, mean 9–19 mm Hg

– PCWP: 4–12 mm Hg (mean) • Cardiac output (CO) = 4.0–6.5 Liters/minute (normal) – This is measured in a PAC by the thermodilution technique, where a known volume and temperature of sterile solution is injected and the change in PA blood temperature is measured by the thermistor. • CO can also be calculated by Fick’s equation = (oxygen consumption)/(10 × arterio-venous oxygen difference) • SvO2 (mixed venous blood oxygenation) = SaO2 – (VO2/[CO × 1.36 × Hb]) – SaO2 = arterial Hb saturation (%)

– VO2 = oxygen consumption (mL O2/min)

– Hb = hemoglobin concentration (g/dL)

GRAPHS/FIGURES

REFERENCES

1. illy LS. ed. Pathophysiology of heart disease. Philadelphia, PA: Lippincott Williams & Wilkins, 2003. 2. Roizen MF, Berger DL, Gabel RA, et al. Practice guidelines for pulmonary artery catheterization: An updated report by the American Society of Anesthesiologists Task Force on Pulmonary Artery Catheterization. Anesthesiology. 2003;99:988–1014. 3. Summerhill EM, Baram M. Principles of pulmonary artery catheterization in the critically ill. Lung. 2005:183–209. 4. Shah MR, Hasselblad V, Stevenson LW, et al. Impact of the pulmonary artery catheter in critically ill patients: Meta-analysis of randomized clinical trials. JAMA. 2005;294(13):1664–1670. 5. Sandham JD, Hull RD, Brant RF, et al. A randomized, controlled trial of the use of

pulmonary-artery catheters in high-risk surgical patients. N Engl J Med. 2003;48(1):5–14.

ADDITIONAL READING

• Binanay C, Califf RM, Hasselblad V, et al. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: The ESCAPE trial. JAMA. 2005;294(13):1625–1633. • Harvey S, Harrison DA, Singer M, et al. Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): A randomised controlled trial. Lancet. 2005;366(9484):472–477. • UptoDate: Pulmonary artery catheterization: Indications and complications; Pulmonary artery catheterization: Interpretation of tracings

See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary embolism • Mitral valve stenosis • Mixed venous oxygen saturation • Cardiac tamponade • Systole • Diastole • Pneumothorax • Cardiac output methods to measure • Pulmonary hemorrhage

CLINICAL PEARLS

• PACs are useful tools in the measurement of hemodynamic parameters, such as cardiac output, mixed venous oxygen saturation, and measurement of pressures in the right heart, PA, and indirectly, the LA. • It can enhance the assessment of hemodynamic status in patients further than clinical assessment alone, and can help guide the administration and management of fluids and vasoactive drugs. • When compared to the echocardiogram, the PAC differs in that it measures pressures (volumes are extrapolated), mixed venous oxygen saturation, and SVR can be calculated; additionally, it can be left in place postoperatively.

PULMONARY ATRESIA Nirvik Pal, MD

BASICS DESCRIPTION

• Pulmonary atresia is a congenital heart defect with pulmonary valve (PV) “closure” that precludes normal blood flow from the right ventricle (RV) to the pulmonary vasculature. It requires some form of a “shunting” method in order to deliver blood to the lungs. There are 2 major categories: – Intact ventricular septum (PA/IVS): Pathology is mostly proximal to the PV, with a small RV and tricuspid valve (TV), as well as RV-dependent coronary blood flow. – Ventricular septal defect (PA/VSD): Pathology is mostly distal to the PV, with discontinuity between the RV and the PA, a misaligned large VSD, and large major aortopulmonary collateral arteries (MAPCA) to the PA or directly supplying the lung lobes. • Multiple staged surgeries are often needed depending on the morphology of the lesion; patients often do not survive without definitive care. EPIDEMIOLOGY Prevalence

• Live births with PA/IVS: 0.07 per 1,000. • PA/VSD accounts for ∼3.4% of all congenital heart defects.

Mortality

Without repair, neonates have a 50% risk and infants up to 6 months have an 85% risk. ETIOLOGY/RISK FACTORS

• Lacks a familial association • Intrauterine right ventricular outflow tract (RVOT) obstruction • Trisomy 18 and 21 may be associated with PA/IVS

PHYSIOLOGY/PATHOPHYSIOLOGY

• Pulmonary atresia is characterized by a maldevelopment of the PV leading to obstruction in normal blood flow from the RV to the lungs for oxygenation and ventilation. In intrauterine life, oxygenation is provided by the mother/placenta, and pulmonary atresia is tolerated. • PA/IVS is characterized by pathology mostly proximal to the PV. This includes a: – Small but hypertrophied RV – Small TV leading to limited blood flow and eventual hypoplasia of the RV. – Tricuspid regurgitation (TR) often results from the structural defect or RV outflow obstruction. If there is no, or minimal, TR, the RV chamber may be small, hypertrophic, and have significant sinusoid formation. In moderate-to-severe TR, low RV pressures may lead to reduced development of sinusoids and fistulae.

– Dilated right atrium – Shunts: Atrial septal defect (ASD) and patent foramen ovale (PFO) are almost always present. A patent ductus arteriosus (PDA) may also be seen. – Blood flow: Sinusoids in the RV myocardium are present in over 50% of patients. The number of sinusoids is increased with higher RV systolic pressures, smaller TV diameter, smaller RV volume, and the absence of, or minimal, TR. There is a “dual” myocardial blood supply from normal aorto-coronary flow and RV-coronary artery fistulae (desaturated venous blood from RV sinusoids). This can result in chronic ischemia of the myocardium. • PA/IVS treatment goals: – Minimize mortality – Promote RV growth – Limit non-definitive surgeries • PA/IVS treatment options: – Complete biventricular repair with closure of the ASD/PFO (40–60% of cases) – Biventricular repair without closure of ASD/PFO – “One-and-half” ventricle repair with cavopulmonary anastomosis – “Single ventricle repair” with total cavo-pulmonary connection (Fontan) – Heart transplantation • PA/IVS surgical techniques are determined by the extent of RV and TV hypoplasia, TR, and the extent of RV-dependent coronary circulation. These techniques include: – RVOT patch annuloplasty with prostaglandin (PG) infusion to keep the PDA open. – RVOT patch annuloplasty with systemic to PA shunt – Pulmonary valvulotomy and systemic to PA shunt • PA/VSD is often considered an “extreme” form of tetralogy of Fallot and the pathology is mostly distal to the PV. There are 4 anatomic subtypes: – (I) Simple valvular or infundibular atresia: Narrowing at the PV or the infundibulum. Often accompanied by a patent PDA. – (II) Absent main pulmonary artery (PA) although continuity of branches of the PA are maintained by PDA-dependent flows. No communication between the RV and the PA exists. – (III) Hypoplastic true PA with multiple major aorto-pulmonary collateral arteries (MAPCA). – (IV) Total absence of a true PA with pulmonary blood flow entirely through MAPCAs. The entire pulmonary blood flow is dependent on these multiple branches from the aorta. • PA/VSD treatment goal is biventricular repair via: – Reconstruction of the pulmonary vascular bed by combining all sources of pulmonary blood supply – Restoration of RV to PA continuity – Closure of the VSD • PA/VSD surgical techniques often are staged procedures and depend on individual morphology: – RV to PA conduit or aortopulmonary window or shunt – Unifocalization or taking all MAPCAs and attaching to a single PA (single or multiple

surgeries) – Definitive intracardiac repair of the VSD • Excess flow through MAPCAs may lead to congestive heart failure (1,2).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Avoid right ventricular decompression (low preload) in patients with RV to coronary blood supply. • Maintain ductal patency with PG infusion. There is an increase in apneic episodes with high PG doses. • The patient may need balloon dilatation of infundibular stenosis or MAPCA embolization in cardiac catheterization suite prior to surgery.

PREOPERATIVE ASSESSMENT SYMPTOMS

Congestive heart failure; edema, shortness of breath, tachypnea, hepatic congestion. History

Cyanosis

Signs/Physical Exam

• Ductal flow murmur: Continuous flow murmur of the PDA. • Single second heart sound

TREATMENT HISTORY

Staged procedures: See above. MEDICATIONS

PG infusion to prevent PDA closure

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• EKG: Right axis deviation, right atrial enlargement • Chest radiography: Normal to low lung vascularity depending on ductal patency. • Echocardiogram: Mainstay of diagnosis, both prenatal and postnatal. • Cardiac catheterization: Confirmation of echocardiogram findings and ruling out of RV to coronary fistulae.

CONCOMITANT ORGAN DYSFUNCTION Trisomy 18 or 21

CIRCUMSTANCES TO DELAY/CONDITIONS Acute congestive heart failure CLASSIFICATIONS

PA/IVS and PA/VSD: See Pathophysiology

TREATMENT PREOPERATIVE PREPARATION

Special Concerns for Informed Consent

• Discuss the potential for postoperative intubation • Blood transfusion consent

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia • For unifocalization procedures, consider thoracic epidural/continuous intercostal nerve block catheters Monitors

• Standard ASA monitors • Arterial line • Central venous line; PA catheters are not utilized due to the structural defects

Induction/Airway Management

• IV or inhalational technique. • Unifocalization procedures often require lung isolation with bronchial blockers.

Maintenance

• MAPCA ligation may lead to desaturation. When this is anticipated, or if the patient has a baseline SpO2 saturation <70%, cardiopulmonary bypass with moderate hypothermia and a beating heart may be considered. In order to prevent cerebral hypoperfusion from pulmonary run-off of oxygenated blood, the maximum possible number of MAPCAs should be ligated before initiating CPB. • After unifocalization procedures, a single cardiac output is perfused through the pulmonary circuit. If the mean PAP is <30 mm Hg, VSD closure is performed. If the mean PAP is >30 mm Hg, a fenestrated closure may be attempted with delayed closure of the fenestration. • Heparin infusions are started after shunt procedures, once surgical bleeding is controlled (1,2). Extubation/Emergence

The decision to extubate depends upon the baseline conditions, intraoperative course (e.g., cardiopulmonary bypass, blood loss), and standard extubation criteria (metabolic status, pulmonary parameters).

FOLLOW-UP

BED ACUITY ICU

MEDICATIONS/LAB STUDIES/CONSULTS • Gradual tapering of PG infusions • Maintain O2 saturation above 70%

• Continue heparin • Reduce RV preload with milrinone or dobutamine • Watch for a “circular shunt”: Blood from the aorta to PA to PDA to RA to incompetent PV, to LA to ASD and returning to the aorta, can result in high output cardiac failure.

COMPLICATIONS

• Shunt thrombosis • Myocardial ischemia particularly in RV-dependent coronary circulation • RV failure • Intrapulmonary bleeding • Reperfusion injury to the lung due to sudden increases in cardiac output • Pulmonary hypertension post unifocalization

REFERENCES

1. Lake CL, Booker PD. Anomalies of pulmonary valves and right ventricular outflow tract. Pediatric Cardiac Anesthesia, 4th ed. Lippincott Williams & Wilkins, 2005. 2. Andropoulos DB, Stayer SA, Russell IA. Anesthesia for right sided obstructed lesion. Anesthesia for Congenital Heart Disease, 2nd ed. Wiley-Blackwell, 2009. 3. Bailey PD Jr, Jobes DR. The Fontan patient. Anesthesiol Clin. 2009;27(2):285–300. 4. Qu JZ. Congenital heart diseases with right-to-left shunts. Int Anesthesiol Clin. 2004;42(4):59–72. 5. Marcelletti CF, Iorio FS. Workshop on “one and one-half” ventricular repairs. Ann Thorac Surg. 1998;66:615. • Yuh DD, Reitz BA. Consensus approach to pulmonary atresia with intact ventricular septum as described by the Congenital Heart Surgeons’ Society (CHSS). Congenital Cardiac Surgery., New York, NY: McGraw-Hill Inc, 2002 (99).

See Also (Topic, Algorithm, Electronic Media Element) • Tricuspid atresia • Cardiopulmonary bypass

CODES ICD9 746.01 Atresia of pulmonary valve, congenital

ICD10

Q22.0 Pulmonary valve atresia

CLINICAL PEARLS

• A thorough understanding of the defect is necessary along with prior surgical “staging” procedures that may have been performed; review studies and discuss with the surgical team or cardiologist for any potential concerns or questions. • In PA/IVS, the management is based upon the extent of the RV-dependent coronary blood supply and RV development. • In PA/VSD, the management is based upon the extent of MAPCAs and successful unifocalization.

PULMONARY EMBOLISM Carlos A. Puyo, MD

BASICS DESCRIPTION

• Pulmonary embolism (PE) may manifest as a cardiovascular emergency secondary to mechanical obstruction and the release of inflammatory mediators in the pulmonary arterial system. • The majority result from blood clots in the pelvic and deep veins of the lower extremities, but can also occur with amniotic fluid, fat, air, and septic emboli. • Intraoperative and postoperative PE can result from venous stasis and inflammatory mediators related to surgery. Additionally, the choice of anesthetic technique (general versus regional) may have an impact on perioperative hypercoagulability. Epidural and spinal anesthesia have been shown to have a decreased incidence of deep venous thrombosis (DVT). • DVT/PE is regarded as an avoidable and preventable event. Thus, anesthesia providers play a role in implementing and ensuring that preventative measures are performed. EPIDEMIOLOGY Prevalence

Annual incidence for DVT is estimated to occur in 23–69 cases per 100,000 surgical cases. Prevalence

• Varies depending on the population studied and coexisting diseases. • PE has been documented in 15–55% of cases after autopsy (death from all causes).

Morbidity

PE may occur in up to 50% of patients with DVT. Mortality

• In the US: 300,000 deaths annually. • If undiagnosed and untreated within 1 hour, 10% of patients may die.

ETIOLOGY/RISK FACTORS

• Acquired factors: – Obesity – Pregnancy and post-partum period – Estrogen use – Surgery: Orthopedic (hip or knee), GI, gynecological, cancer. – Age 40 years and older – Trauma: Fractures (hip or leg).

– Spinal cord injury – Malignancy: Secondary to chemotherapy, hormone therapy. – Prolonged immobilization: Travel, surgery – Central venous catheters – Antiphospholipid antibody syndrome – Polycythemia vera • Hereditary factors: – Protein C and S deficiency – Antithrombin III deficiency – Factor V Leiden – Prothrombin gene mutation – Dysfibrinogenemia – Plasminogen deficiency • Other factors: – History of DVT, heparin-induced thrombocytopenia (HIT), varicose veins. – Medical conditions such as: Congestive heart failure (CHF), arrhythmia, respiratory failure, and inflammatory disease (bowel, rheumatoid arthritis).

PHYSIOLOGY/PATHOPHYSIOLOGY

• Mechanical obstruction: PE may have various degrees of obstruction within the pulmonary circulation depending on the number and location of emboli. This can result in: – Dead space ventilation (ventilation without perfusion) – Increased right ventricular afterload – Pulmonary infarct • Inflammatory mediators: Additionally, obstructive material may set off an inflammatory cascade that releases vasoactive products and serotonin. The effect is a constellation of: – Pulmonary edema – Shunting (impaired alveolar ventilation secondary to atelectasis) and hypoxemia – Increased airway resistance (wheezing) – Increased minute ventilation – Decreased vital capacity – Decreased diffusing capacity – Tachycardia and hypotension • In severe cases, right ventricular dysfunction and respiratory collapse may result secondary to an elevation in wall tension, ventricular dilation, and ischemia. Cardiogenic shock and myocardial ischemia may occur.

PREVENTATIVE MEASURES

• Avoid prolonged immobilization • Heparin/low-molecular-weight heparin (LMWH) may be administered preoperatively/postoperatively. Since most antithrombotic drugs are renally excreted, caution must be observed when administering to patients with renal dysfunction. LMWH has a better therapeutic profile than unfractionated heparin (UFH) and may provide superior DVT prophylaxis in high-risk surgical groups (trauma, hip, and knee replacement). • Intermittent pneumatic compression devices and elastic stockings applied during the

perioperative period have shown benefit in patients with a moderate risk for DVT or with a known contraindication for anticoagulation. • An inferior vena cava (IVC) filter is indicated if there is a recent diagnosis of DVT/PE and the patient is unable to receive anticoagulation. • Utilize adjuvant therapies for pain management such as intravenous analgesics (PCA) or local regional techniques (nerve blocks, epidural, spinal, and wound infiltration). Regional techniques may control acute pain for hours to days depending on the technique used. Epidural and spinal anesthesia may decrease the rates of DVT, likely as a result of sympathetic blockade with improvement in circulation and decrease in hypercoagulability. • Fat emboli occurrence can be minimized with early treatment of the underlying cause: Surgical repair of long bone fractures, careful monitoring of fat content in total parenteral nutrition infusions, and surgical repair of cardiac wall defects (PFO). • Septic emboli must be ruled out in patients with persistent fever and positive blood cultures. A search for the embolic source (e.g., heart valves) is important in guiding therapeutic decisions.

Pregnancy Considerations

• The risk of PE is ∼15 times higher in the postpartum period than during pregnancy, and is likely related to venous stasis, alterations in circulating clotting factors (I, II, VII, VIII, IX, and X), declines in protein S, increased platelet activation, and elevated fibrin production. The therapeutic approach is the same as the non-pregnant patient. • Amniotic fluid emboli prevention requires avoidance of any uterine trauma (surgical and nonsurgical) or spontaneous rupture.

PREOPERATIVE ASSESSMENT • Clinical findings include tachycardia, tachypnea, calf pain or swelling, cough, hemoptysis, chest pain/pleural rub, increased jugular pressure, or syncope (lacking sensitivity and specificity) • Location: Central vascular zones include the main pulmonary artery, left and right main pulmonary arteries, anterior trunk, right and left interlobar arteries, left upper lobe trunk, right middle lobe artery, and right and left lower lobe arteries. Peripheral vascular zones include the segmental and subsegmental arteries of the right upper lobe, right middle lobe, right lower lobe, left upper lobe, lingula, and left lower lobe. • Extent: A PE is considered to be massive when it involves both pulmonary arteries or results in hemodynamic compromise. • Pre-test risk stratification is important for diagnosis and treatment. The Wells (2) and Geneva (3) scores factor in risk factors and clinical findings and may aid in guiding further diagnostic work-up. • Computerized tomography (CT) scan. A spiral chest CT scan produces a 3-D image by rotating the scanner around the body in a spiral and has a greater sensitivity (and is quicker) than plain CT imaging (2-D). Contrast material may be injected to provide delineation of the pulmonary vasculature and improve definition of nonvascular structures (CT angiogram). However, contrast may be harmful to the kidneys. • Pulmonary angiography use is reserved for cases requiring a catheter-based treatment.

• Ventilation-perfusion (V/Q) lung scanning is an alternative to CT angiography if contrast dye is a concern. Highly sensitive in patients without cardiopulmonary disease. • Compression ultrasonography can detect proximal DVT in 20% of patients with PE; they have a high sensitivity and specificity for proximal DVT of the lower extremities (evidence grade A). • Chest radiography is useful to rule out acute conditions such as hemothorax and pneumothorax. • Echocardiography is an alternative if the patient is too unstable for transport. TEE has a sensitivity of 60–80% and specificity of 95–100%. TTE is useful in detecting right ventricular dysfunction. Findings include abnormalities in ventricular wall motion, ventricular dilation, paradoxical septal motion, tricuspid insufficiency, elevated pulmonary artery pressure, and IVC congestion. • PA catheter may be considered for management and differential diagnosis purposes. • ECG may have an S1, Q3, T3 pattern consistent with acute cor pulmonale. Right bundle branch block (RBBB) and right axis deviation may also be present. ECG findings in PE are neither specific nor sensitive. Helpful in MI diagnosis during an acute hemodynamic crisis. • Arterial blood gas analysis is useful to evaluate hypoxemia, hypercarbia, and can aid with the differential diagnosis of PE. • D-dimer levels: If there is a low pre-test probability, a negative test can be useful to rule out a PE (strong negative predictive value).

DIFFERENTIAL DIAGNOSIS • Congestive heart failure • Pulmonary hypertension • Acute coronary syndrome

TREATMENT • Intravenous anticoagulation: – Heparin enhances the activity of antithrombin III, which inhibits thrombin and other factors such as Xa, IXa, XIa, and XIIa. Thrombin also inhibits factors V, VIII, and thrombin-induced platelet activation. Initial treatment of PE and DVT consists of a heparin bolus (80 U/Kg) with a maintenance dose (18 U/Kg); aPTT levels should be titrated to 1.5–2.5 times normal levels or a plasma concentration of 0.3–0.7 IU/L within 24 hours. Current evidence suggests treatment for 5–6 days in combination with oral therapy (evidence level A). – LMWH are derived from heparin after chemical and enzymatic depolymerization to create shorter compounds that have a decreased ability to combine with other molecules. Enoxaparin 1 mg/kg SQ q12 hours or 1.5 mg/kg SQ QD can be used for the treatment of PE and DVT (has been shown to be as effective as heparin for PE, and more effective for DVT). LMWHs have the benefit of SQ administration, lower rates of HIT, and do not require routine laboratory monitoring. If monitoring is necessary (obesity, pregnancy, renal failure), anti-factor Xa levels are checked. • Oral anticoagulation:

– Warfarin inhibits the enzymes that convert vitamin K epoxide to reduced vitamin K. The initial dose for PE and DVT treatment is 5–10 mg daily with individual factors requiring dose adjustments. INR levels should be titrated to a level of 2.0–3.0 for venous thromboembolism (VTE) for 2 consecutive days prior to the discontinuation of heparin. Treatment for 3 months is recommended for PE due to reversible causes (evidence level A). • Thrombolytic therapy (urokinase, streptokinase, alteplase) is indicated in proven cases of PE with cardiogenic shock. They rapidly dissolve thrombus, but carry significant risk of intracranial bleeding. It has the greatest benefit if used within 48 hours of the onset of symptoms. • Thrombin inhibitors: If HIT is suspected, consider therapy with argatroban, lepirudin, or bivalirudin. • Catheter-based pulmonary embolectomy and local intraembolic thrombolytic therapy can be lifesaving. Surgical embolectomy can be considered in patients with free-floating thrombi in the right atrium.

FOLLOW-UP • Acute intraoperative PE should be suspected in any patient with a strong preoperative history suggestive of DVT. • Intraoperative TEE (transesophageal echocardiogram) may be helpful with the diagnosis of PE.

REFERENCES

1. Konstantinides S. Clinical practice. Acute pulmonary embolism. N Engl J Med. 2008;359:2804–2813. 2. Wells PS, Anderson DR, Rodger M, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: Management of patients suspected of pulmonary embolism presenting to the emergency department by using a simple clinical model and D-Dimer. Ann Intern Med. 2001;135:98–107. 3. Le Gal G, Righini M, Roy PM, et al. Prediction of pulmonary embolism in the emergency department: The revised Geneva score. Ann Intern Med. 2006;144:165–171. 4. Tapson VF. Acute pulmonary embolism. N Engl J Med. 2008;358:1037–1052. 5. Hirsch J, Guyatt G, Albers GW, et al. Antithrombotic and thrombolytic therapy: American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines Executive Summary. Chest. 2008;133:71S–105S. See Also (Topic, Algorithm, Electronic Media Element) • Dead space • Venous air embolism • D-dimer

CODES

ICD9

415.19 Other pulmonary embolism and infarction ICD10

I26.99 Other pulmonary embolism without acute cor pulmonale

CLINICAL PEARLS

• Diagnosis and treatment of PE requires a high index of suspicion and rapid risk stratification. • Hemodynamically unstable patients require immediate evaluation to exclude sepsis, hypovolemia, and new onset arrhythmia. If the initial assessment is negative, they are regarded as high risk for PE. • Prevention is essential in hospitalized patients with the use of heparin, LMWH, warfarin, and/or sequential compression devices.

PULMONARY FUNCTION TESTS Ilka Theruvath, MD, PhD Sylvia H. Wilson, MD

BASICS DESCRIPTION

• Pulmonary function tests (PFTs) measure lung volumes, airflow, and diffusing capacity of gas across the alveolar–capillary membrane (DLCO). • Lung volumes and capacities refer to the volume of air associated with different phases of the respiratory cycle.

FIGURE 1. Lung volumes and capacities.

• Lung volumes are directly measured. They include: – Tidal volume (TV), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), and residual volume (RV). • Lung capacities are composed of one or more lung volumes. They include: – Inspiratory reserve capacity (IRC), vital capacity (VC), total lung capacity (TLC), and functional residual capacity (FRC). • Forced expiratory spirometry measures expiratory flow and volume while the patient forcefully exhales after maximal inhalation.

FIGURE 2. Forced expiratory spirometry.

PHYSIOLOGY PRINCIPLES

• TV: Volume of air inspired with passive breathing. – Normal TV: ∼6–8 mL/kg – TV decreases with decreased lung compliance and/or reduced ventilatory muscle strength. • IRV: Maximal volume of air that can be additionally inspired after a normal tidal inspiration. – Normal IRV: ∼1.9–3.3 L • ERV: Maximum volume of air forcibly expired after a normal tidal expiration. – Normal ERV: ∼0.7–1 L • RV: Volume of air remaining in the lungs after forceful expiration. It cannot be exhaled, and hence cannot be measured on routine spirometry. – Normal RV: ∼1 L • Inspiratory capacity (IC): Volume of air inspired with maximum lung expansion after resting expiration. – IC = IRV + TV (normal ∼2.5 − 3.5 L) – Reduced IC can signify extrathoracic airway obstruction. • FRC: Volume of gas remaining in the lungs after passive expiration. – FRC = ERV + RV (normal ∼1.8 − 2.3 L) – FRC influences the ventilation–perfusion relationship within the lung. – Reduced FRC leads to an increase in venous admixture and arterial hypoxemia. – Indirect determination of FRC (because RV cannot be measured on spirometry). Equilibration method: FRC is calculated by the equilibration of a tracer gas (helium) in a closed-circuit system. Using a spirometer and starting at FRC, the patient breathes a given concentration of helium and oxygen. Helium equilibrates between the patient’s lungs and the spirometer. Since the system is closed, FRC can be determined by (Concentration1 × Volume1) = (Concentration2 × Volume2). Washout method: FRC is calculated from the washout of a tracer gas (nitrogen) within the lungs. The patient breathes 100% oxygen for several minutes to “wash out” alveolar nitrogen. Nitrogen fractional concentration and expired volume is measured over 7 minutes. The initial and final alveolar nitrogen fractional concentrations and the nitrogen concentration in the collected expirate are used to calculate FRC. Plethysmography: The patient sits in a box with a pressure transducer and breathes through a mouthpiece. The mouthpiece is connected to an electronic shutter and a

differential pressure pneumotachometer. Mouth pressure and box pressure changes are measured during tidal breathing and panting maneuvers. The differential pressures are used to calculate thoracic gas volume and FRC. • VC: The maximum volume of air that can be exhaled after maximal inspiration. – VC = IRV + TV + ERV (normal ∼60 mL/kg) – VC correlates with the ability for deep breathing and effective coughing. • TLC: The volume of air within the lungs after maximum inspiratory effort. – TLC = IRV + TV + ERV + RV (normal ∼ 5 L) • Forced vital capacity (FVC): The volume of air exhaled with maximal expiration after maximal inspiration. – FVC normally equals VC. – FVC measurements are dependent on patient effort and cooperation. • Forced expiratory volume in 1 second (FEV1): The volume of air exhaled forcefully in the

first second of an FVC maneuver. – Measure of flow (volume expired over time). – Dependent on patient effort. Low FEV1 may be a result of inadequate effort, not lung

disease. • FEV1/FVC: Normalizes FEV1 measurements to the patient’s individual lung volume.

– Normal FEV1/FVC ≥ 0.75; the volume of air that is expired in 1 second should be 75% of

the forced vital capacity. • Forced midexpiratory flow rate (FEF25-75%): Exhaled volume between 25% and 75% of FVC.

– Formerly called the maximum midexpiratory flow rate (MMFR). – Less effort dependent than FEV1 or FVC, but may be reduced by submaximal inspiration

(decreased FVC) or markedly decreased expiratory effort. – Normal values vary widely due to the dependence on FVC. Both the absolute value (normal ∼ 2–5 L/sec) and the percentage of predicted value (normal ∼ 100% ± 25%) are recorded. • Diffusing capacity (DLCO): Measures the diffusion of carbon monoxide (CO) across the alveolar–capillary membrane. Diffusion capacity is determined by measuring the partial pressure difference between inspired and expired CO. – DLCO reflects the diffusing capacity of physiologic gases, such as oxygen and carbon dioxide. • Maximum voluntary ventilation (MMV): Largest volume that can be breathed in 1 minute by voluntary effort. – MMV records the patient breathing as rapidly and deeply as possible for 10 seconds by a pneumotachograph and the results are extrapolated to 1 minute. – Best indicator of ventilatory muscle endurance.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Obstructive lung disease: Asthma, chronic bronchitis, emphysema, bronchiolitis, and chronic obstructive pulmonary disease (COPD). – Diminished expiratory airflow from collapse of small airways. Decreased FEV1/FVC and FEF25-75%.

– Airway collapse during expiration causes air trapping with subsequent hyperinflation. Increased TLC, FRC, RV. • Restrictive lung disease: Intrinsic and extrinsic pulmonary processes. – Intrinsic (loss of alveolar airspace): Pulmonary fibrosis, sarcoidosis, or pneumonia. – Extrinsic (reduction of lung space): Scoliosis, disorders of thoracic cage, pleural effusion, pneumothorax, or neuromuscular disorders. – Smaller lung volumes along with normal or decreased expiratory flow (decreases to a lesser extent than volume). Normal or increased FEV1/FVC and FEF25-75% – Reduction of all lung volumes, especially TLC, VC, and RV. • Compromise of alveolar capillary unit: Loss of lung parenchyma (emphysema or COPD), thickening of the alveolar–capillary membrane (interstitial lung disease or pulmonary fibrosis), or pulmonary vascular disease. – Reduction of DLCO

PERIOPERATIVE RELEVANCE

• Patients undergoing general anesthesia and surgical procedures (particularly thorax and upper abdomen) develop changes in pulmonary function that may contribute to postoperative pulmonary complications. – VC is reduced up to 25–50% of preoperative values after open thorax or upper abdominal procedures and remains depressed for 10–14 days. – FRC decreases by 10–15% in the supine position. • The primary goal of preoperative PFTs is to recognize patients at high risk of postoperative pulmonary complications. – Reduced FVC values (<15 mL/kg) are associated with postoperative pulmonary complications (1). Most commonly seen in quadriplegics or severe neuromuscular disease. Reduced FVC is associated with ineffective cough and development of atelectasis. • PFTs provide some predictive benefit in patients undergoing lung resection. – Predicted postoperative FEV1 calculated by multiplying the preoperative FEV1 by the

percentage of lung tissue expected to remain after resection. An increased risk of perioperative pulmonary morbidity is associated with a predicted postoperative FEV1 <30% (2).

EQUATIONS

• IC = TV + IRV; where IC is inspiratory capacity, TV is tidal volume, and IRV is inspiratory reserve volume • FRC = ERV + RV • VC = IRV + TV + ERV; where VC is vital capacity, ERV is expiratory reserve volume, and IRV is inspiratory residual volume • TLC = VC + RV; where TLC is total lung capacity, VC is vital capacity, and RV is residual volume

REFERENCES

1. Qaseem A, Snow V, Fitterman N, et al. Risk assessment for and strategies to reduce perioperative pulmonary complications for patients undergoing noncardiothoracic surgery: A guideline from the American College of Physicians. Ann Int Med. 2006;144(8):575–580. 2. Bapoje SR, Whitaker JF, Schulz T, et al. Preoperative evaluation of the patient with pulmonary disease. Chest. 2007;132(5):1637–1645. 3. Task force on preanesthetic evaluation. Practice advisory for preanesthesia evaluation: A report by the American Society of Anesthesiologists. Anesthesiology. 2002;96(2):485–496.

ADDITIONAL READING

• Stock MC. Respiratory Function in Anesthesia. In: Barash PG, ed. Clinical Anesthesia. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:804–807.

CLINICAL PEARLS

• Preoperative PFTs help clinicians diagnose previously unknown lung diseases and allow the assessment of the severity of known lung diseases. • While PFTs are well established in the preoperative workup of patients undergoing pulmonary resections, it is not recommended for routine preoperative evaluation (3). • PFTs should not be used in isolation to determine if a patient is ineligible for surgical intervention. Rather, it should be utilized in conjunction with other assessments of cardiopulmonary functions such as history, physical examination, exercise testing, arterial blood gas analysis, chest radiography, ventilation–perfusion scintigraphy, and split-lung function studies as indicated.

PULMONARY HEMORRHAGE Gerard R. Manecke Jr., MD

BASICS DESCRIPTION

• Pulmonary hemorrhage is a life-threatening emergency characterized by severe, acute lung bleeding. It may cause gas exchange problems, airway obstruction, and hemodynamic compromise. • In the perioperative period, it: – May be present as a medical emergency in which an anesthesia provider is asked to assist airway management. – May occur intraoperatively as an acute process or complication (surgery, pulmonary artery catheterization, airway management). EPIDEMIOLOGY Prevalence

Rare complication that is reported in <1% of anesthetics Prevalence

• Ongoing pulmonary hemorrhage is very rare (it either resolves, is treated successfully, or the patient succumbs to it). • Conditions predisposing to it, such as fungal infection or tuberculosis (TB) are rare, with the prevalence dependent upon the specific population. Morbidity

• Blood or clot in the airway may cause airway/endotracheal tube obstruction. • Blood loss may cause hypovolemia or hemorrhagic shock.

Mortality

High and can exceed 50% depending upon the etiology as well as the timeliness and effectiveness of treatment. ETIOLOGY/RISK FACTORS

• Pulmonary infection – Cavitary TB (“Rasmussen’s aneurysm”) – Fungal infection • Bronchiectasis • Wegener’s granulomatosis: A vasculitis affecting the nose, ears, kidneys, and lungs. • Goodpasture’s syndrome: An autoimmune disease affecting the kidneys and lungs. • Hydrostatic gradient bleeding – Negative pressure in airway obstruction (1)[C]

– Severe acute pulmonary hypertension • Pulmonary vessel trauma – Thoracic trauma – Pulmonary artery catheter (PAC) placement

PHYSIOLOGY/PATHOPHYSIOLOGY

• Diffuse pulmonary hemorrhage results from: – Infectious processes with widespread pulmonary capillary or arterial breakdown (e.g., capillaritis). – Large pulmonary capillary–alveolar hydrostatic gradient (severe pulmonary hypertension, negative pressure from airway obstruction). • Localized bleeding usually results from trauma, with the exception of cavitary infections such as TB. – Pulmonary artery rupture – Complication of pulmonary thromboendarterectomy (2)[C]

PREVENTATIVE MEASURES

• PACs must be used with care. – “Wedge” the catheter only for good reason. – Withdraw the catheter 1–2 cm prior to inflating the balloon. – Remove the catheter gently, as there have been case reports of accidental suturing to the PA wall during cardiac surgery. General rule: If something is not easy to remove, do not use force!

PREOPERATIVE ASSESSMENT • Blood appears in the airway – Dark blood usually indicates pulmonary arterial bleeding. – Bright red blood usually indicates bronchial (systemic) arterial bleeding. • History and records may reveal: – History of fungal or tuberculous infection – Recent chest trauma – Recent PAC placement – Difficult removal of a double lumen endobronchial tube after pneumonectomy (may have been accidentally sutured in place during surgery) – Difficult pulmonary thromboendarterectomy with disruption/perforation of a pulmonary artery (2)[C] • Fiberoptic bronchoscopy (FOB) is recommended to determine the source of bleeding (diffuse vs. lobar process, left vs. right). It may be necessary to perform a rigid bronchoscopy when the flexible scope is inadequate.

DIFFERENTIAL DIAGNOSIS

• Pulmonary edema with severe capillary leak may have a hemorrhagic component. • GI bleeding (hematemesis) • Nasopharyngeal or oropharyngeal bleeding

TREATMENT • Supportive modalities: – Control the airway with placement of an endotracheal tube. Use the largest ETT feasible to allow for effective suctioning and bronchoscopy. – Provide oxygen and ventilation. – Positive airway pressure (e.g., PEEP) may help tamponade bleeding. – Consider lung isolation to keep the bleeding localized and preserve gas exchange in uninvolved lung segments (maintain V/Q matching). Double lumen endobronchial tubes are excellent for lung isolation. However, suctioning and FOB may be difficult because of the smaller lumens. In addition, if an endotracheal tube is already in place, it should only be removed with great caution; airways may be edematous and intubation may become difficult or impossible, even with exchange catheters. Bronchial blocker (ArndtTM, UniventTM, Fogarty catheter). However, it is not feasible to maintain lung isolation while performing a bronchoscopy or suctioning. – Correct coagulopathy if it is present. – Transfuse red blood cells as necessary • Therapeutic modalities – Consider topical vasoconstrictor; can be delivered either via an endotracheal tube or locally via FOB. Vasopressin (2 U/mL, 20 mL) Phenylephrine (100 mcg/mL, 20 mL) Epinephrine (5 mcg/mL, 20 mL) – Embolization of the bleeding bronchial artery or balloon occlusion of the pulmonary artery may be performed by interventional radiologists (4)[C]. – Consider lung resection or pneumonectomy for localized bleeding refractory to other treatments.

FOLLOW-UP • After bleeding resolves, the assistance of the anaesthetist may be required for: – Removal of the bronchial blocker – Exchange of double lumen tube with a single lumen endotracheal tube – Weaning from mechanical ventilation and extubation

CLOSED CLAIMS DATA

• Since it is rare, there are few closed claims data on pulmonary artery hemorrhage during anesthesia. – 2 cases of pulmonary artery rupture from PAC out of a total of 3,533 claims in the ASA Closed Claims Database: http://depts.washington.edu/asaccp/ASA/index.shtml

REFERENCES

1. Dolinski SY, MacGregor DA, Scuderi PE. Pulmonary hemorrhage associated with negative-

pressure pulmonary edema. Anesthesiology. 2000;93:888–890. 2. Manecke GR Jr, Kotzur A, Atkins G, et al. Massive pulmonary hemorrhage after pulmonary thromboendarterectomy. Anesth Analg. 2004;99:672–675. 3. Huang GS, Wang HJ, Chen CH, et al. Pulmonary artery rupture after attempted removal of a pulmonary artery catheter. Anesth Analg. 2002;95:299–301.

4. Dopfmer UR, Braun JP, Grosse J, et al. Treatment of severe pulmonary hemorrhage after cardiopulmonary bypass by selective, temporary balloon occlusion. Anesth Analg. 2004;99:1280–1282. 5. Carron H, Hill S. Anesthetic management of lobectomy for massive pulmonary hemorrhage. Anesthesiology. 1972;37:658–659.

ADDITIONAL READING

• Manecke GR Jr, Kotzur A, Atkins G, et al. Massive pulmonary hemorrhage after pulmonary thromboendarterectomy. Anesth Analg. 2004;99:672–675.

See Also (Topic, Algorithm, Electronic Media Element) • Double lumen tube • One lung ventilation

CODES ICD9 786.30 Hemoptysis, unspecified ICD10 R04.89 Hemorrhage from other sites in respiratory passages

CLINICAL PEARLS

• Pulmonary hemorrhage is life-threatening; asphyxia is the most common cause of death. • The most common causes are infection and pulmonary vessel trauma. • Impaired gas exchange leading to hypoxia and hypercarbia along with airway obstruction is common. • Diagnosis often involves FOB to localize the source of bleeding. • Treatment often involves tracheal or endobronchial intubation, continuous airway pressure, topical vasoconstrictors, and bronchial blockade.

PULMONARY HYPERTENSION Nirvik Pal, MD Anand Lakshminarasimhachar, MBBS, FRCA

BASICS DESCRIPTION

• Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure > 25 mm Hg. Pulmonary artery hypertension is also defined as pulmonary vascular resistance (PVR) > 3 Wood units (240 dynes s/cm5) (1). It can result from chronic disturbances or diseases in pulmonary venous and arterial pressures, cardiac output, or left atrial pressures. – Primary PH: Due to intrinsic pathology of reactive pulmonary vasculature. – Secondary PH: As a result of some other primary pathology of lung, heart, or systemic diseases. • The pulmonary vasculature is often responsive to hypoxia, hypercarbia, acidosis, and noxious stimuli such as airway instrumentation or suctioning; in PH, it may be hyperreactive. Increased pulmonary artery pressures can result in RV dysfunction, ischemia, and failure, as well as systemic hypotension, and cardiac arrest. EPIDEMIOLOGY Prevalence

• New cases of primary PH in the US: ∼300/year • New cases of secondary PH in the US: ∼1,000/year

Prevalence

• Primary PH in the US: 1:906,666 • Secondary PH in the US: 1:272,000

Morbidity

Increased incidence of prolonged intubation, ICU stay, and length of hospital stay Mortality

Higher perioperative mortality in both cardiac and non-cardiac surgeries due to the increased incidence of pulmonary embolism, heart failure, deep vein thromboses, ARDS, etc. ETIOLOGY/RISK FACTORS See classifications

PHYSIOLOGY/PATHOPHYSIOLOGY

• Resistance = pressure/flow (1) – Therefore, PVR = (PAP − LAP)/CO – Alternatively, PAP = LAP + (CO * PVR), where PVR is pulmonary vascular resistance,

PAP is pulmonary artery pressure, LAP is left atrial pressure, CO is cardiac output • Depending upon the etiology, PH may result from a rise in the left atrial pressure, right heart blood flow, pulmonary vascular resistance, or a mix of these conditions. • Increased left atrial pressure (as may be seen with left ventricular failure, long-standing mitral stenosis, or severe mitral regurgitation) increases the “afterload” of the pulmonary vasculature. • Increased right heart blood flow, from “shunting” or “mixing” cardiac lesions (atrial septal defect, ventricular septal defect) increases flow through the pulmonary vasculature with a resultant increase in pulmonary pressure. • Increased PVR or pulmonary arterial hypertension (PAH) can result from vasoconstriction, cellular proliferation, thrombosis, and apoptosis in pulmonary arteries. At a molecular level, this is often mediated by nitric oxide, endothelin, prostacyclin, serotonin pathways, or genetic constitution like BMPR2, ALK-1, or 5-HTT mutations. • With time, PH results in right ventricular hypertrophy or dilation, followed by dysfunction or failure due to: – High RV afterload – RV ischemia from hypoperfusion during systole (normally RV perfusion happens both in systole and diastole) due to elevated PA pressure – Systemic hypotension from interventricular septal shifting of the dilated RV that leads to restricted LV filling

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The anaesthetist needs to be aware of the underlying pathophysiology and severity of the disease, as well as assess if the patient is currently optimized. The RV status should be determined and the use of pulmonary vasodilators may be necessary. • Perioperative goals include avoidance of hypoxia, hypercarbia, coughing, and bucking during induction or emergence; in addition, appropriate volume status, cardiac output, and systemic BP need to be maintained. • In PH, TPG = mPAP – PCWP; where TPG is transpulmonary gradient, mPAP is mean pulmonary artery pressure, and PCWP is pulmonary capillary wedge pressure. If the TPG >12 mm Hg, PH may be due to high PVR; if the TPG <12 mm Hg, PH may be due to left heart failure.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Fatigue, weakness • Dyspnea • Angina can result from an imbalance in oxygen supply and demand

History

• Palpitations from arrhythmias • Syncopal events from hypotension or arrhythmias (due to dilated heart chambers)

Signs/Physical Exam

• Edema from RV or LV failure • Jugular venous distension • Clubbing may indicate congenital heart disease or chronic lung disease • Cyanosis

TREATMENT HISTORY

• Supplemental oxygen • Medication pump installed to continuously deliver pulmonary vasodilators • Lung transplantation (or awaiting one)

MEDICATIONS

• Anticoagulation: Perioperative management should be discussed with the surgeon and primary physician. In addition, it may preclude neuraxial anesthesia. • Diuretics can affect electrolytes and volume status • Contraception: Severe PH is considered unsafe for labor and delivery. • Calcium channel blockers provide systemic and pulmonary vasodilation; may be useful in reversible PH • Phosphodiesterase inhibitors (PDE-5i) • Endothelial receptor antagonist (ETRA)

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Autoantibody tests: Scleroderma, SLE, RA, vasculitis • Liver function tests: May be elevated from hepatic congestion • Chest radiograph: May show emphysema or prominent lung vasculature • EKG: RV enlargement, right axis deviation, right heart strain pattern • Echocardiogram: Right ventricular function, congenital heart disease • Pulmonary function tests: Chronic lung disease • Sleep study: Obstructive sleep apnea • V/Q scan: Chronic thromboembolic disease • Right heart catheterization can reveal the status of the RV function, PA pressures, and congenital heart lesions. • Left heart catheterization for LV function and transpulmonary gradient. Vasodilator tests can show the reversibility of PH and is performed during catheterization using inhaled prostaglandin or nitric oxide; utilized to help plan subsequent therapy. CONCOMITANT ORGAN DYSFUNCTION

• Liver dysfunction • Left heart disease • Arrhythmias from dilated chambers

CIRCUMSTANCES TO DELAY/CONDITIONS Acute RV ischemia, dysfunction, or failure CLASSIFICATIONS

• World Health Organization classification of PH (Venice, 2003) (2): – (I) Pulmonary hypertension: Idiopathic, familial, associated with diseases (congenital heart disease, collagen vascular disease, portal hypertension, HIV, drugs, toxins) – (II) PH secondary to left heart disease: Left-sided hypertension or ventricular heart disease. – (III) PH secondary to lung disease with or without hypoxemia: Interstitial lung disease, chronic obstructive pulmonary disease, sleep-disorders, alveolar hypoventilation disease, chronic exposure to altitude – (IV) PH secondary to thrombotic or embolic disease: Thromboembolic obstruction of the proximal or distal pulmonary arteries – (V) Miscellaneous: Sarcoidosis, histiocytosis X

TREATMENT PREOPERATIVE PREPARATION Premedications

• Sedation can result in hypoxia or hypercarbia and exacerbate PH; if used, judicious administration, supplemental oxygen, and pulse oximetry is recommended. • Supplemental oxygen

Special Concerns for Informed Consent

Postoperative intubation should be discussed INTRAOPERATIVE CARE Choice of Anesthesia

• Sedation • Regional: Platelet inhibition may result from systemic pulmonary vasodilators like prostacyclin • General anesthesia

Monitors

• Standard ASA monitors • Arterial line placement for beat-to-beat BP monitoring and frequent ABGs; consider placing pre-induction • Central line placement for measurements of central venous pressures that can reflect changes in PAP, RV, or LA pressures • Pulmonary artery catheter may be indicated in severe disease, or when the underlying cause is due to left heart disease • TEE depending on the complexity of surgery

Induction/Airway Management

• Sedation should implement supplemental oxygen via nasal cannula, face mask, or nonrebreather as appropriate. • Regional techniques should implement supplemental oxygen if sedation is given; neuraxial

techniques can result in sympatholysis and should be dosed appropriately. Epidural catheters allow for slow bolusing and time to treat hemodynamic changes. Balance the need for preoperative fluid boluses with the potential for CHF. • General anesthesia: A laryngeal mask airway (LMA) may be used, but has the potential for hypercarbia; consider pressure support modes to maintain volumes. Endotracheal tube (ETT) allows for greater control of ventilatory parameters, and is often chosen. • Avoid hypotension with induction; consider etomidate (avoid ketamine), high dose narcotic technique, concurrent inotropic or vasopressor treatment. Avoid hypercarbia with adequate bag mask ventilation. Avoid hypoxia by appropriately pre-oxygenating, limiting duration of laryngoscopy. Avoid noxious responses to airway instrumentation by ensuring that the patient is adequately induced prior to any airway instrumentation. Avoid nitrous oxide as it can increase pulmonary vascular resistance.

Maintenance

• Ventilation strategy is aimed at avoiding hypoxia, hypercarbia, and increased thoracic pressures (3). – Tidal volumes: Maintaining ventilation at optimal functional residual capacity is essential. Tidal volumes that are too high or too low may lead to increased PVR either due to compression of overdistended alveoli or atelectasis. – PaCO2: Maintain at normal or mild alkalosis by increasing RR or TV; weigh against the potential to increase mean pulmonary pressures – PaO2: Increase FIO2, PEEP to reduce atelectasis (need to balance PEEP levels against the

increase in thoracic pressures). • Inhaled pulmonary vasodilators (nitric oxide, prostacyclin [PGI2]) are often preferred to

systemic vasodilators as these agents have the added benefit of maintaining hypoxic pulmonary vasoconstriction. Since they are delivered via the inhalation route, they only vasodilate vessels that are perfusing ventilated alveoli; which prevents desaturation by avoiding pulmonary blood flow to non-ventilated areas of the lung. • Maintain systemic BP for adequate RV perfusion. • Careful monitoring of RV function; reductions may require the use of inotropic drugs such as phosphodiesterase inhibitors that bestow inotropy with afterload reduction (e.g., milrinone). Dobutamine and dipyridamole may also be utilized. • Prevent and treat metabolic acidosis. • Maintain an adequate level of anesthesia and analgesia to blunt sympathetic or stress responses. • Fluid administration needs to be monitored as excess fluid may precipitate ventricular failure and pulmonary edema.

Extubation/Emergence

Coughing, bucking, bearing down can result in excessive pulmonary pressures. Deep extubation with continued ventilatory support via bag mask may be considered to avoid this.

FOLLOW-UP

BED ACUITY

• Bedside telemetry at a minimum is usually needed. • ICU/HDU care may be necessary in severe disease, intraoperative events, inotropic support, or pulmonary vasodilator treatment.

MEDICATIONS/LAB STUDIES/CONSULTS

• Pulmonary and/or cardiology consult; consider having a discussion with the patient’s specialist who is managing their disease prior to the procedure to discuss any recommendations and establish good follow-up. • Inhaled vasodilators (nitric oxide or prostacyclin)

REFERENCES

1. ritts CD, Pearl RG. Anesthesia for patients with pulmonary hypertension. Curr Opin Anesthesiol. 2010;23:411–416. 2. McLaughlin V, McGoon M. Pulmonary artery hypertension. Circulation. 2006;114:1417– 1431. 3. Blaise G, Langleben D, Hubert B. Pulmonary arterial hypertension: Pathophysiology and anesthetic approach. Anesthesiology. 2003;99:1415–1432. 4. Farber H, Loscalzo J. Pulmonary artery hypertension. N Engl J Med. 2004;352:1655–1665. 5. Hoeper MM, Barbera JA, Channick RN, et al. Diagnosis, assessment and treatment of nonpulmonary arterial hypertension pulmonary hypertension. J Am Coll Cardiol. 2009;54(suppl 1):S85–S96. 6. Memtsoudis SG, Ma Y, Chiu YL, et al. Perioperative mortality in patients with pulmonary hypertension undergoing major joint replacement. Anesth Analg. 2010;111(5):1110–1116. 7. Ramakrishna G, Sprung J, Ravi BS, et al. Impact of pulmonary hypertension on the outcomes of noncardiac surgery. J Am Coll Cardiol. 2005;45(10):1691–1699. 8. Reich DL, Bodian CA, Krol M, et al. Intraoperative hemodynamic predictors of mortality, stroke, and myocardial infarction after coronary artery bypass surgery. Anesth Analg. 1999;89:814–822. 9. Van Wolferen S, Marcus JT, Boonstra A, et al. Prognostic value of right ventricular mass, volume, and function in idiopathic pulmonary arterial hypertension. Eur Heart J. 2007;28:1250–1257. See Also (Topic, Algorithm, Electronic Media Element)

• Obstructive sleep apnea

CODES ICD9 • 416.0 Primary pulmonary hypertension • 416.8 Other chronic pulmonary heart diseases

ICD10

• I27.0 Primary pulmonary hypertension • I27.2 Other secondary pulmonary hypertension

CLINICAL PEARLS

• A thorough understanding of the underlying pathophysiology, severity, and current treatment of PH. • Maintain systemic BP. • Reduce pulmonary artery pressure. • Monitor right ventricle function.

PULMONARY VASCULATURE Ali Salehi, MD

BASICS DESCRIPTION

• The pulmonary vasculature is a vascular bed that delivers non-oxygenated blood from the right ventricle to the lungs, facilitates gas exchange at the alveolar level, and delivers oxygenated blood to the left atrium. • It is a high-flow, low-pressure system. Pulmonary vascular endothelium is exposed to the whole cardiac output (CO) and has a surface area of 200 m2. Compared to the systemic circulation, its resistance is lower secondary to a higher compliance of peri-capillary pulmonary arterioles (thinner media, fewer smooth muscle cells). Normal pulmonary artery pressure (PAP) is 1/5th that of systemic arterial pressure (SBP). • Histologically, like all other vessels, pulmonary vessels consist of 3 layers: Intima (endothelium), media (smooth muscle), and adventitia. PHYSIOLOGY PRINCIPLES

• Oxygenation: Although gas exchange can theoretically occur in any pulmonary vascular wall, under normal conditions, little O2 and CO2 exchange occurs before the true pulmonary

capillaries. As blood enters the capillary bed, it loses velocity because of a sudden increase in the overall surface area from arterioles (1 m2) to capillaries (50–70 m2), though it is still pulsatile due to the low vascular resistance. The capillary network has considerable length, crossing several alveoli of the terminal respiratory unit before forming a venule. The length of the capillary network, together with the large surface area of the pulmonary capillary bed, provides reasonable transit time (~0.5–1 seconds) for the red blood cells. This allows sufficient time for equilibrium between oxygen and carbon dioxide tensions to occur in the alveoli and the capillary bed. • Reservoir: Functions as a reservoir between the right and left heart. There is sufficient blood volume in the pulmonary vascular bed to enable moderating the changes in right ventricular output over 2–3 beats. • Blood filter: 75% of the circulating blood is in the venous system; the pulmonary microvasculature is the first vascular bed that blood flows through. A moderate amount of microemboli have no detectable effect on the pulmonary vascular bed due to the presence of multiple parallel pathways in the microcirculation. • Physiologic factors: – CO: Increases in the CO recruit previously closed vessels and distend open vessels with a resultant increase in the overall pulmonary vascular surface area and decrease in the PVR. – Ventilation: PVR is at its maximum with small lung volumes (constriction of extra-alveolar vessels) as well as large lung volumes (compression of alveolar vessels). PVR is at its minimum at the functional residual capacity (FRC). This results in a “U”-shape relationship between PVR and lung volumes.

– Alveolar oxygen: Increases in alveolar oxygenation result in pulmonary vasodilatation, whereas alveolar hypoxia results in pulmonary vasoconstriction (hypoxic pulmonary vasoconstriction; HPV). HPV serves to divert blood flow from poorly ventilated areas of the lung to the better ventilated areas, which improves the ventilation/perfusion matching. – CO2 and pH: CO2 exerts no direct effect on the pulmonary vasculature, but increases the

hydrogen ion concentration. Decreasing the pH results in pulmonary vasoconstriction and increased PVR. – Autonomic nervous system: Pulmonary vasculature shows less vasomotor response to autonomic stimulation than the systemic vasculature. • Pulmonary vasodilators: Pulmonary vascular endothelium mediates smooth muscle tone, pulmonary vascular resistance (PVR), and PAP in response to different stimuli through vasodilator and vasoconstrictor activity. Vasodilators include: – Nitric oxide (NO) synthase activity converts L-arginine to L-citrulline and releases NO. NO diffuses to pulmonary vascular smooth muscle where it increases the activity of guanylate cyclase which converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and increases the cytoplasmic levels of cGMP. cGMP mediates relaxation of vascular smooth muscle and vasodilatation. Phosphodiesterase-5 (PDE-5) catalyzes the breakdown of cGMP, thus limiting the duration of vasodilatation. – Activation of cyclooxygenase enzyme results in the production of prostacyclin (PGI2) from arachidonic acid. PGI2 diffuses to smooth muscles (SMCs) and upregulates the activity of

adenylate cyclase and conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). cAMP mediates relaxation of vascular smooth muscle (SM) and vasodilatation. – Phosphodiesterase-3 (PDE-3) catalyzes the breakdown of cAMP and limits the time of vasodilatation. It has been shown that PDE-3 is inhibited by cGMP. – Cyclic nucleotides activate specific protein kinases which decrease the influx of Ca++ into the SM and decrease the sensitivity of the SM contractile apparatus to Ca++. • Pulmonary vasoconstriction is mediated via several mechanisms: Prostaglandin F2α and Prostaglandin A2; endothelin stimulates production of growth factors; serotonin promotes smooth muscle proliferation and hyperplasia; angiotensin binds AT1 receptors, increasing intracellular calcium and stimulating protein kinase C (7).

ANATOMY

• The main pulmonary artery divides at the level of the sternal notch to the left and right branches entering the relative hilum. Each pulmonary artery then divides into lobar arteries which accompany the corresponding bronchi. Subsequently, the lobar arteries and bronchi branch into segmental arteries and bronchi followed by arterioles and end in alveolar capillaries. • The alveolar capillaries are lined with non-fenestrated endothelial cells. The overall surface area of the capillary endothelium is 130 m2. Water and solutes pass through the capillary bed through receptor-mediated uptake or transcellular transport. The latter is usually restricted by tight junctions.

• Two pulmonary veins (superior and inferior) on each side carry the oxygenated blood from the lungs to the left atrium. They run independently of the arteries and the bronchi in the lungs. • Due to high PVR in utero, only 5–10% of the right ventricular CO goes through the lungs and the remainder is diverted into the systemic circulation through the patent ductus arteriosus (PDA). After birth and the first breath, NO and PGI2 are released in response to increased oxygen levels and the productions of ATP from the oxygenated red blood cells. This results in a rapid drop in PVR and a 10-fold increase in pulmonary blood flow along with the closure of the patent foramen ovale (PFO) and the PDA.

DISEASE/PATHOPHYSIOLOGY

• Pulmonary edema occurs when fluid enters the alveoli faster than it is removed and can result in impaired gas exchange and hypoxemia. The Starling equation cites the factors that govern fluid transit in the lungs. The driving force for fluid filtration in the lungs is the balance between the transmural hydrostatic pressures (Pc–Pi) and the colloid osmotic pressures (πc–πi). The actual amount of filtrate that is produced depends on the integrity of

the barrier to filtration (Lp) and reflection (σd) coefficients. The safety factors that protect

the lungs from edema include the lung lymphatic system, resorption into blood vessels, drainage into the mediastinum and pleural space, and active transport by alveolar and distal airway epithelial cells. – Pulmonary edema results from increases in driving pressures (increased pressure edema), barrier conductance (increased permeability edema), or both. Barrier permeability differentiates the two and is normal in increased pressure edema and abnormal in increased permeability edema. – Increased lung microvascular hydrostatic pressure can result from left ventricular dysfunction, mechanical obstruction of left atrial outflow (mitral stenosis), volume overload, pulmonary venous hypertension, or increased lymphatic outflow pressure. – Re-expansion pulmonary edema can be seen in patients with a collapsed lung (pneumothorax, hemothorax) after placement of chest tube and removal of air and fluid, or in patients undergoing thoracic surgery and lung isolation. This is thought to be due to the generation of negative intrathoracic pressure and ischemia-reperfusion injury. Upon reperfusion, not only are free radicals and inflammatory mediators released, which increase the permeability of the basement membrane, but PVR also shifts more toward the postcapillary venules and increases hydrostatic pressure in the capillary bed. • Endothelial dysfunction: Inflammation, acidosis (in the setting of infection), hypoxemia, increased CO (pregnancy, anemia, hyperthyroidism), and elevated pressures (left ventricular failure, mitral stenosis/regurgitation, pulmonary venous occlusion) can lead to endothelial dysfunction. It can result in a decrease in endothelium-derived NO, and prostacyclin as well as an increase in thromboxane and endothelin-1 with resultant pulmonary vasoconstriction, SM proliferation, and platelet aggregation. Platelet aggregation leads to in situ thrombosis and release of serotonin and plasminogen activator inhibitor (decrease in fibrinolytic activity) which exacerbate pulmonary vasoconstriction and rise in PVR. Endothelin and serotonin cause fibroblast proliferation, collagen deposition in the adventitia, and

hyperplasia and hypertrophy of the pulmonary vascular smooth muscle. If the underlying condition is not treated and controlled, it will lead to pulmonary hypertension.

PERIOPERATIVE RELEVANCE

• Patients with a risk of pulmonary edema (congestive heart failure, renal failure, liver failure) should be carefully evaluated and optimized prior to surgery. Excess fluid can be removed with the use of diuretics or dialysis. Perioperative volume administration should be performed with caution to provide adequate preload but to avoid volume overload and pulmonary congestion. • Patients undergoing thoracic procedures with lung isolation are at a higher risk for reexpansion pulmonary edema. • Negative pressure pulmonary edema can be seen during extubation (more common in young healthy patients). The generation of large negative intrathoracic pressures with concurrent upper airway obstruction result in either “pulling” of fluids from the pulmonary capillary bed into the alveoli (Starling forces) or injury to the pulmonary microvascular membranes from severe mechanical stress that results in capillary “leaking” of fluid. • Persistent hypoxemia can result in a sustained rise of PAP and vascular remodeling. PVR rises as the PaO2 decreases below 60 mm Hg. Hence, supplemental oxygen is a cornerstone

of management of patients with pulmonary hypertension. • During mechanical ventilation in patients with pulmonary hypertension or other pulmonary pathology, attention to the “U”-shape relationship between lung volumes and PVR is important in selecting appropriate tidal volumes. Optimal tidal volume is closer to FRC, which results in the lowest PVR and avoids intrapulmonary shunting (small tidal volume) and decreased pulmonary perfusion (large tidal volumes). • Pulmonary hypertension – NO, prostacyclin analogs (Epoprostenol, Iloprost), endothelin inhibitors (Bosentan), PDE-3 antagonists (milrinone, amrinone) and PDE-5 antagonists (sildenafil) are the cornerstones of management of patients with pulmonary hypertension based upon the mechanisms discussed before. Most of these drugs are used in the perioperative management of these patients. – Patients with pulmonary hypertension should be closely monitored. All attempts should be made to prevent any sudden rise in PVR and PAP which can lead to RV failure. These include adequate oxygenation, hyperventilation (in intubated patients with close attention to tidal volume and respiratory rate) with a goal end-tidal CO2 of 35–40 mm Hg, correction of acidosis (respiratory/metabolic), adequate pain control (to attenuate sympathetic response), maintenance of normothermia and euvolemia.

EQUATIONS

• Starling equation for microvascular barrier: Jv = LpS [(Pc − Pi) − σd (πc − πi)] – Jv is net fluid filtration rate across the microvascular barrier – Lp is the hydraulic permeability of the barrier

– S is the surface area of the barrier – Pc is pulmonary capillary hydrostatic pressure

– Pi is interstitial hydrostatic pressure

– πc is the capillary (microvascular) plasma colloid osmotic (or oncotic) pressure

– πi is the interstitial (perimicrovascular) fluid osmotic pressure

– σd is the average osmotic reflection coefficient of the barrier (a measure of how effective the barrier is in hindering the passage of solutes from one side of the barrier to the other).

REFERENCES

1. Rubinfire M, Bayram M, Hector-Word Z. Pulmonary hypertension in the critical care setting: Classification, pathophysiology, diagnosis, and management. Crit Care Clin. 2007;23(4):801–834.

2. Fischer LG, Van Aken H, Bürkle H. Management of pulmonary hypertension: Physiological and pharmacological considerations for anesthesiologists. Anesth Analg. 2003;96(6):1603– 1616. 3. Brimioulle S, Vachiery JL, Brichant JF, et al. Sympathetic modulation of hypoxic pulmonary vasoconstriction in intact dogs. Cardiovasc Res. 1997;34(2):384–392. 4. Wojciak-Stothard B, Haworth SG. Perinatal changes in pulmonary vascular endothelial function. Pharmacol Ther. 2006;109(1–2):78–91. 5. MacKnight B, Martinez EA, Simon BA. Anesthetic management of patients with pulmonary hypertension. Semin Cardiothorac Vasc Anesth. 2008;12(2):91–96. 6. effner JE. Mechanisms underlying ischemia/reperfusion injury of the lung. In: Matthay MA, Ingbar D, eds. Pulmonary edema. New York, NY: Marcel Dekker; 1998:379–341. 7. Higuchi S, Ohtsu H, Suzuki H, et al. Angiotensin II signal transduction through the AT1 receptor: Novel insights into the mechanisms and pathophysiology. Clin Sci. 2007;112(8):417–428.

ADDITIONAL READING

• Mason: Murray and Nadel’s textbook of Respiratory Medicine, 5th ed. Volume 1, Chapter 1: Anatomy of the Lungs, Pulmonary Circulation. • Mason: Murray and Nadel’s textbook of Respiratory Medicine, 5th ed. Volume 2, Chapter 55: Pulmonary Edema and Acute Lung Injury.

See Also (Topic, Algorithm, Electronic Media Element) • Negative pressure pulmonary edema • Cardiogenic pulmonary edema • Acute respiratory distress syndrome

CLINICAL PEARLS

• The pulmonary vasculature is an active bed that is under the control of numerous mediators and physiologic functions. In addition, if functions as a blood reservoir, filtration system, and metabolizes several drugs.

PULMONARY VENTILATION–PERFUSION MATCHING Ana Maria Manrique-Espinel, MD Todd M. Oravitz, MD

BASICS DESCRIPTION

• Ventilation is defined as the mechanism of gas flow through the lungs that allows exchange of oxygen into and carbon dioxide out of the system. • Perfusion is defined as the mechanism of blood flow through the lungs that allows uptake of oxygen into red blood cells and simultaneous removal of carbon dioxide; it functions to transport gases from tissue to lung and vice versa. • The relationship between ventilation (V) and perfusion (Q) determines gas exchange. The ideal V/Q ratio is 1; however, there are physiologic regional differences and the average V/Q ratio is 0.8 (4 liters/minute compared to 5 liters/minute). – Upper lung areas receive more ventilation relative to perfusion; therefore V > Q and V/Q > 1 – Lower lung fields receive more perfusion relative to ventilation; therefore V < Q and V/Q < 1 PHYSIOLOGY PRINCIPLES

• Matching: Under physiologic states, ventilation and perfusion are not equally distributed within the lung. – Ventilation: Minute ventilation (MV) is the product of tidal volume and respiratory rate; in the average adult, MV is ∼4 L/min. – Perfusion: The lungs accept the entire cardiac output (CO). Thus, blood flow to the lungs is equal to stroke volume multiplied by heart rate; in the average adult, CO is ∼5 L/min. – Regional differences in V, Q, and hence matching, exist normally in the lungs as a result of gravitational and non-gravitational factors. • Gravitational forces. – Ventilation: Gas more readily distributes to the apex of the lungs; the alveoli are bigger and there is less resistance to inflow. – Perfusion: Blood more readily distributes to the base of the lungs secondary to gravity. • Non-gravitational forces. – Ventilation: Intrinsic anatomic variation of the airways, lung volumes, or airway resistance which are dependent upon pleural hydrostatic gradients, regional compliance, and bronchial anatomy. – Perfusion: Dependent upon differences between the arterial pulmonary pressure, arterial venous pressure, and interstitial and alveolar pressures. Studies suggest that hydrostatic forces are the most important influence on V/Q and result in more central flow compared to peripheral flow. Mapping of the lung has shown an “onion distribution” of the perfusion; perfusion is greatest at the hilum and decreases towards the periphery.

• Zones: 4 areas of ventilation/perfusion distribution have been described: – Zone 1: Apex of the lung. The alveolar pressure is greater than both pulmonary arterial and venous pressures. – Zone 2: Middle of the lung. Pulmonary arterial pressure exceeds alveolar pressure. Blood flow will depend on the difference between arterial and alveolar pressures and, in fact, is independent of venous pressure (unless it is higher than alveolar pressure). – Zone 3: Base of the lung. Arterial and venous pressures are higher than alveolar. Blood flow is continuous and will increase with increases in the hydrostatic pressure. – Zone 4: Describes a physiologic zone, not an anatomic zone, where the vessels are decreased in diameter and there is increased resistance to blood flow. Occurs at high and low lung volumes as well as increased interstitial pressures. • Oxygen and carbon dioxide: The oxygen content and composition of the gases follow the mass conservation law in which the total oxygen content of the blood is equal to the sum of the pulmonary capillary oxygen content and the oxygen content in the shunt. Variations in V/Q determine the composition of the gases at each level of the lung, as well. Arterial oxygen pressure (PaO2) is higher in the apex and the arterial carbon dioxide (PaCO2) is lower. The oxygen uptake is higher in the lower base of the lung because this is the area where there is more flow (most efficient). • Measuring V/Q: The gold standard is the multiple inert gas elimination technique “MIGET." Most recently single-photon emission computed tomography has been used “SPECT”

ANATOMY

• Regional flow – Blood flow is higher in the dorso-caudal areas of the lung compared with ventrocephalad areas. – “Onion distribution” describes the preferential perfusion to the hilum of the lung, decreasing toward the periphery. – The right lung receives more ventilation and perfusion in the upright and supine position than the left lung. • Regional ventilation: – Apices have bigger alveoli. Lower zones of the lung have smaller, more compliant alveoli that facilitate air entry. – Gas exchange is better in the dependent areas of the lung regardless of the position. – The shape of the thoracic cavity is also an important influence in the differences in the regional ventilation.

DISEASE/PATHOPHYSIOLOGY

• Dead space refers to areas of the lung that are ventilated but have no blood flow. V/Q = V/0 = ∞ – Anatomical dead space: Volume of gas occupying the conducting airways where there is no gas exchange; it may be affected by the size of the subject, age, posture, and position of the neck. Normal dead space is ∼150 mL (∼2 mL/kg). – Alveolar dead space: Volume of gas that passes through the alveoli but does not perform effective exchange. This may occur due to a lack of perfusion to the alveoli. The alveolar dead space can increase significantly when there is low CO, pulmonary embolism, or

inadequate settings for mechanical ventilation in the lateral position. – Physiologic dead space (VD) is the sum of all parts of the tidal volume that do not

participate in gas exchange (anatomical plus alveolar dead space). Normally, this comprises ~30% of the tidal volume; in pediatrics it reaches close to half of the tidal volume. – Aging produces an increase in the vascular resistance of the small capillaries and fibrosis of the interstitium that interferes with gas exchange;as a consequence, elderly patients have increased heterogeneity of ventilation and perfusion of the lung. Also the decreased elastic recoil in some areas produces collapse of alveoli and decreased ventilation. • Shunt – Physiologic shunt: Describes blood that travels through the pulmonary vasculature but does not contact ventilated alveoli (atelectasis concept). V/Q = 0/Q = 0. In pediatrics, the physiologic shunt is increased ~10%. – Anatomic shunt: Describes blood that bypasses the lungs through an anatomic channel such as the bronchial veins, Thebesian veins, and right- to-left shunts (ventricular septal defect).

PERIOPERATIVE RELEVANCE

• General anesthesia: – Spontaneous ventilation: The diaphragm function is impaired and there are increases in physiologic shunting (decreased FRC). – Mechanical ventilation and muscle relaxation: Ventilation is greater in the upper portions of the lung (less resistance to flow); whereas, the blood flow is greater in the dependent portions of the lung. • Position: In the awake, spontaneously ventilating patient, distribution of ventilation in the upright lung was shown to vary somewhere between 6–24%. When supine, the variation through the lung derived from the gravitational forces is small. Under general anesthesia: – Supine: Cephalad movement of the diaphragm and abdominal contents results in decreased FRC; there is decreased ventilation to the base of the lung, while perfusion continues. – Trendelenburg: Accentuated cephalad movement of the diaphragm and abdominal contents; decreased ventilation to the base of the lung, with continued but decreased perfusion (secondary to gravitational forces). – Reverse Trendelenburg: Gravity results in caudal displacement of the diaphragm and abdominal contents with resultant improvement to ventilation in this area. Perfusion to the base is increased due to gravitational forces – Lateral: Both ventilation and perfusion are greater in the dependent lung. • Hypoxic pulmonary vasoconstriction (HPV): Occurs in normal lung, under hypoxemic conditions to decrease shunting. Low oxygen pressures are sensed in the pulmonary endothelium, causing the release of calcium from the sarcoplasmic reticulum, which results in vasoconstriction. There is evidence of inhibition of HPV from inhaled anesthetics. Thus, hypoxic or poorly ventilated alveoli will continue to be perfused. • Pulmonary disease: The effects of general anesthesia and mechanical ventilation may have a significant impact in ventilation/perfusion matching. Patients should be carefully assessed

preoperatively for risk stratification and implementation of maneuvers that may decrease postoperative pulmonary complications. • One lung ventilation (OLV): Changes depend on: – Awake and breathing spontaneously: Ventilation is dominant in the dependent (lower) lung, along with perfusion. – General anesthesia and mechanical ventilation: Following clamping (onset of OLV), ventilation will be directed to the dependent lung, with the non-dependent or operative side compressed. Perfusion will follow the hydrostatic pressure, being more prominent in the dependent lung. However, a significant right- to- left shunt is created in the nondependent lung, because it continues to be perfused.

EQUATIONS

• Alveolar ventilation equation: VA = f (VT - VD); where VT is tidal volume, VD is dead space ventilation, and f is the frequency of breaths. • Alveolar gas equation: PAO2 = PIO2 – PaCO2/R; where PAO2 = partial pressure of oxygen in the alveoli PIO2 = partial pressure of oxygen in the inspiratory gas; PaCO2 = partial

pressure of carbon dioxide in the artery; and R = the respiratory exchange ratio or VCO2/VO2.

• Ventilation/perfusion ratio equation: VA/Q = 8.63R

• (CaO2 − CvO2) / PaO2; where CaO2 = arterial oxygen content; CvO2 = venous oxygen content.

REFERENCES

1. Evans AM, Hardie DG, Peers C, et al. Hypoxic pulmonary vasoconstriction: Mechanisms of oxygen-sensing. Curr Opin Anaesthesiol. 2011;24(1):13–20. 2. opkins SR, Arai TJ, Henderson AC, et al. Lung volume does not alter the distribution of pulmonary perfusion in dependent lung in supine humans. Physiol. 2010;588(Pt 23):4759– 4768. 3. Taylor BJ, Johnson BD. The pulmonary circulation and exercise responses in the elderly. Semin Respir Crit Care Med. 2010;31(5):528–538. 4. King GG, Harris B, Mahadev S. V/Q SPECT: utility for investigation of pulmonary physiology. Semin Nucl Med. 2010;40(6):467–473. 5. Salome CM, King GG, Berend N. Physiology of obesity and effects on lung function. J Appl Physiol. 2010;108(1):206–211. 6. Glenny RW. Determinants of regional ventilation and blood flow in the lung. Intensive Care Med. 2009;35(11):1833–1842.

ADDITIONAL READING

• Pulmonary physiology. Michael G. Levitzky. 7th ed. McGraw Hill 2007 Chapter 5 Ventilation–Perfusion relationships. 113–129. • Respiratory Physiology. John B west. 8th ed. Lippincott 2008 – Chapter 5 Ventilation–

Perfusion relationships—How matching of gas and blood determines gas exchange. 55–74.

See Also (Topic, Algorithm, Electronic Media Element) • Dead space • Postoperative pulmonary complications • One lung ventilation

CLINICAL PEARLS

• Changes in mechanical ventilation settings, position of the patient, and hemodynamics are factors that can be manipulated to achieve adequate ventilation–perfusion matching.

PULSE OXIMETRY Gundappa Neelakanta, MD

BASICS DESCRIPTION

• The pulse oximeter noninvasively estimates the percentage of hemoglobin–oxygen saturation in the arterial blood. • Expressed as SpO2%.

• Functions as a measure of how much oxygen is bound to hemoglobin, as a percentage of the maximum carrying capacity. • The two-part probe is applied over a reasonably translucent site with good blood flow, such as the finger or ear lobe. • Comprised of an emitter that produces light on one end and a photodetector on the other end; the tissue lies in between.

PHYSIOLOGY PRINCIPLES

• Delivery of oxygen to the tissues by the blood is dependent on: The total oxygen-carrying capacity of blood, cardiac output, and blood flow to the tissues. Almost all of the oxygen carried in the blood is bound to hemoglobin. Only a small amount is present in the dissolved form due to the low solubility coefficient (0.003 mL of oxygen per dL of blood per mm Hg PaO2). Conversely, each gram of hemoglobin carries 1.34 mL of oxygen when completely saturated. Note: The percent oxygen saturation of hemoglobin is in equilibrium with and dependent on the PaO2 of blood.

• Oxyhemoglobin curve: Used to describe the relationship between the PaO2 and oxygen saturation. Some important numbers to remember include: – PaO2 760 mm Hg = SpO2 100%

– PaO2 100 mm Hg = SpO2 97.4% Increasing the PaO2 > 100 mm Hg will not significantly increase the oxygen-carrying capacity. – PaO2 70 mm Hg = SpO2 93%

– PaO2 28 mm Hg = SpO2 50% (known as the P50)

• Sigmoidal shape: The hemoglobin molecule favors oxygen loading in the lungs and unloading to the tissues. – The upper part of the curve is almost flat; thus, the PaO2 in the lungs (alveoli) has to drop

<70 mm Hg before a significant change in the hemoglobin saturation of oxygen can occur. This provides a margin of safety. – The steep portion between a PaO2 of 10–40 mm Hg represents how a small change in the PaO2 will result in larger changes in oxygen saturation. This serves a critical physiologic

function in peripheral tissues where the PaO2 is very low. Thus, slight changes in the PaO2

will result in greater unloading of oxygen to the tissues.

See Table • P50: Describes the PaO2 at which the hemoglobin saturation is 50%. The binding and dissociation of oxygen to hemoglobin can be affected by several factors including: pH, PaCO2, temperature, and 2,3 diphosphoglycerate (2,3 DPG). These changes result in right

and left shifting of the oxy-hemoglobin curve. – Right shifting refers to a decreased oxygen affinity to hemoglobin; a greater PaO2 is

required to saturate the hemoglobin molecule. Physiologic conditions include acidosis, as well as, higher PaCO2 levels, temperatures, and 2,3 DPG levels; such conditions are

prevalent in peripheral tissues and facilitate the unloading of oxygen. The relatively flat upper portion of the curve is less affected, thus minimizing the impact on the loading of oxygen in the lungs. – Left shifting refers to an increased oxygen affinity to hemoglobin; a smaller PaO2 is required to saturate the hemoglobin molecule. Physiologic conditions include alkalosis, as well as decreases in PaCO2, temperatures, and 2,3 DPG.

• The principle of pulse oximetry is based upon the differential light absorption characteristics of oxygenated and deoxygenated hemoglobin. – Oxyhemoglobin absorbs more infrared light at wavelength of 840 nm. – Reduced deoxyhemoglobin absorbs more red light at a wavelength of 680 nm. – Transmission method: The emitter and photodetector are on opposite sides from each other. The transmitted red (R) and infrared (IR) signals are received at the photodetector, and the R/IR ratio is calculated and converted into a SpO2% value. – Arterial pulsations result in a momentary increase in blood volume across the measuring site and enhance light absorption. An algorithm differentiates absorbance between static tissue components (e.g., venous flow, bone, skin, muscle, etc) and dynamic arterial flow. • Limitations in pulse oximeters can result in false readings, false alarms, data drop outs, and missed desaturations from: – Motion artifacts

– Irregular heart rhythms – Electrocautery interference – Intense ambient light interference – Poor signals during low perfusion or poor perfusion states – Vasopressor use – Cold periphery – Some types of nail varnishes

ANATOMY

• The optically shielded probe is usually applied to finger tips or ear lobes. Occasionally, it can also be applied to the buccal mucosa or ala of the nares in situations of poor perfusion. • These probes contain light emitting diodes applied on one side of the finger and a sensor on the opposite side. The probes may get significantly warmed and need to be changed in vulnerable populations: preemies or neonates.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Decreased cardiac output: Results in decreased oxygen delivery to the tissues (causes include reduced cardiac preload, heart failure, and shock). With anemia, pulse oximeter SpO2% may

be normal; however, there may be decreased oxygen delivery to the tissues. • Hypoxia: Mechanisms may be broadly categorized as due to low inspired oxygen concentration, hypoventilation, ventilation–perfusion mismatch, shunt, and low cardiac output. Various medical conditions such as pneumonia, pneumothorax, and pulmonary embolism cause hypoxia often by a combination of the above-mentioned mechanisms. • Dyshemoglobins: Can affect the accuracy of the conventional two wavelength pulse oximeter readings. – Methemoglobin will read at 85% oxygen saturation regardless of actual levels. Pulse oximeters measure two wavelengths of light: 660 nm (red, oxyhemoglobin) and 940 nm (infrared, deoxyhemoglobin). Methemoglobin absorbs equal amounts of these wavelengths; a ratio of pulsatile and nonpulsatile absorbances equal to 1 corresponds to a hemoglobin saturation of 85%. Normal methemoglobin levels are <1%. – Carboxyhemoglobin and oxyhemoglobin have similar absorption characteristics. Its presence will give falsely elevated readings and therefore is clinically significant. Carboxyhemoglobin does not carry oxygen and also affects dissociation of oxygen to the tissues. Usual carboxyhemoglobin levels are <1.5% in non-smokers, and higher in city dwellers, and can be as high as 3–15% in smokers. – Fetal hemoglobin will not affect the accuracy of estimation of hemoglobin saturation. HgF, however, does cause a shift in the oxyhemoglobin dissociation curve to the left (binds oxygen more tightly resulting in higher saturations at lower PaO2 levels). Consequently, there is decreased “off-loading” of oxygen at peripheral tissues. – Effects of sickle cell hemoglobin are controversial with some studies showing large errors and others minimal.

PERIOPERATIVE RELEVANCE

• Pulse oximetry allows for the immediate recognition of hypoxia and has contributed to the

safety of modern anesthesia and intensive care management. It is a routinely used monitor in most clinics, every operating room, and perioperative and intensive care unit across the US and the western world. – Shows excellent correlation with the measured co-oximeter hemoglobin SpO2 above 75%.

– Used during patient transport as well as in procedure rooms where sedation is administered. – Used during intrapartum monitoring of the fetus, neonatal resuscitation, and premature neonates to limit pulmonary oxygen toxicity and retrolental fibroplasia. • Specialty sensors – Congenital heart disease: Sensors have been developed that show greater correlation with saturations as low as 60%. – Parameters such as the pleth variability index (PVI), have been derived from the variation in the plethysmographic waveform during ventilation. This may be helpful in the goaldirected administration of intravenous fluids during perioperative management. – Newborn sensors have been developed that can measure the high pulse rate, as well as provide maximum sensitivity that allows for quick application of monitor information. – Specialized monitors exist to detect carbon monoxide poisoning in the field by firefighters and emergency medical technicians (EMT), as well as diagnosis and monitoring of treatment in the emergency rooms.

EQUATIONS

Delivery of O2/min = CO (mL/min) × (hemoglobin concentration in gm/dL × 1.34 ×

SpO2) + (0.003 × PaO2 in mm Hg).

REFERENCES

1. arker SJ, Badal JJ. The measurement of dyshemoglobins and total hemoglobin by pulse oximetry. Curr Opin Anaesthesiol. 2008;21:805–810. 2. Wukitsch MW, Petterson MT, Tobler DR, et al. Pulse oximetry: Analysis of theory, technology, and practice. J Clin Monit. 1988;4:290–301. 3. Pedersen T, Moller AM, Hovhannisyan K. Pulse oximetry for perioperative monitoring. Cochrane Database Syst Rev. 2009;7(4):CD002013. 4. Chapman KR, Liu FL, Watson RM, Rebuck AS. Range of accuracy of two wavelength oximetry. Chest. 1986;8(4):540–542. 5. Josten KU. Oximetry. Br J Anaesth. 1986;58(2):248–249. 6. May WS Jr. Respiratory monitoring. Int Anesthesiol Clin. 1986;24(1):159–169.

ADDITIONAL READING

• Barrett KE, Barman SM, Boitano S, Brooks H, “Chapter 36. Gas Transport & pH in the Lung” (Chapter). Barrett KE, Barman SM, Boitano S, Brooks H: Ganong’s Review of Medical Physiology, 23e.

See Also (Topic, Algorithm, Electronic Media Element)

• Methemoglobinemia • Oxygen-carrying capacity • Intraoperative hypoxia • Mixed venous oxygen saturation

CLINICAL PEARLS

• The pulse oximeter will only reveal hemoglobin’s oxygen saturation; it does not provide PaO2 values. Therefore, pulse oximetry should be interpreted with caution, where monitoring of the PaO2 is critical (e.g., fetal or neonatal monitoring).

• The SpO2% does, however, provide an indirect measure of the PaO2 when the partial

pressure is <100 mm Hg. • Pulse oximeter readings may be normal, but the oxygen-carrying capacity of blood may be severely reduced in the presence of anemia.

PULSELESS ELECTRICAL ACTIVITY J. Scott Bluth, BS Nina Singh-Radcliff, MD

BASICS DESCRIPTION

• Pulseless electrical activity (PEA), previously known as electromechanical dissociation (EMD), is defined as electrical depolarization of the heart in the absence of synchronous cardiac myocyte shortening. New evidence suggests that it is a heterogenous clinical condition with varying levels of BP and cardiac activity: – Pseudo PEA: Severe hypotension, no clinically detectable pulses, residual cardiac activity. – True PEA: BP and cardiac wall motion are completely absent. • Treatment requires initiation of advanced cardiac life support (ACLS) with concurrent diagnosis and treatment of the underlying cause; this approach has not evolved in decades. Recent increases in the incidence of PEA have aroused interest and the development of animal models to better understand the pathogenesis in order to improve therapies and survival. • Anaesthetists must be aware of potential, common perioperative events that could incite PEA such as hypoxia, hypovolemia, potassium abnormalities, hypothermia, acidosis, and concomitant beta-blocker and calcium-channel blocker use; as well as pulmonary embolism, hypoglycemia, cardiac tamponade, tension pneumothorax, and coronary artery thrombosis. EPIDEMIOLOGY Prevalence

• Comprises ∼35–40% of all in-hospital cardiac arrests • Comprises ∼22–30% of all out-of-hospital cardiac arrests • Pseudo-PEA data not available

Morbidity/Mortality

• In-hospital PEA cardiac arrests: 11% survival, of which 62% had good neurologic outcomes. • Out-of-hospital arrests: 2.5% survival to discharge. • Outcomes following PEA were slightly better than those following asystole.

ETIOLOGY/RISK FACTORS

PEA and other forms of cardiac arrest are often caused by a set of reversible conditions conveniently referred to as the “H’s” and “T’s.” These factors should be considered and corrected as quickly as possible while life-saving efforts are being performed. • Hypoxia (common perioperative cause) • Hyperkalemia or hypokalemia • H+ ions (acidemia) • Hypovolemia (common perioperative cause)

• Hypothermia • Hyperglycemia • Tamponade • Tension pneumothorax • Thrombosis, coronary • Thrombosis, pulmonary • Toxins (poisoning) • Trauma

PHYSIOLOGY/PATHOPHYSIOLOGY

• Electrical depolarization is typically followed by mechanical contraction and blood ejection from the ventricles. This sequence is fast and elegant; however, there are several clinical conditions that can impede it. • The H’s and T’s involve cardiac, respiratory, and metabolic disturbances with a common end-point: Electrical activity without a meaningful pulse. The exact pathogenesis remains unclear; however, evidence suggests that myocardial ischemia is the common pathophysiologic insult, either by decreased preload or cardiac contractility. – Decreased preload may result from hypovolemia, tension pneumothorax, tamponade, or pulmonary thrombosis. – Decreased cardiac contractility may result from hypoxia, hypothermia, potassium abnormalities, acidosis, or coronary thrombosis. • Global myocardial ischemia can consequently result in hypoxia, acidosis, and increased vagal tone. These disturbances are believed to cause depolarization and the uncoupling of excitation and contraction with resultant PEA. – Hypoxia results in anaerobic metabolism and lactic acidosis, with resultant hyperkalemia. It has negative inotropic effects. – Intracellular acidosis from hypoxia and the build-up of metabolic by-products may be responsible for impairing calcium affinity to troponin C. It has negative inotropic effects. – Increased vagal tone can reduce heart rate and BP. • Animal studies have suggested that calcium uptake following reperfusion may be involved in, or is the result of, PEA. A significant uptake of calcium into myocardial cells is followed by swelling, damage to mitochondria and myofibrils, and deposits of intramitochondrial calcium phosphate. The increased calcium uptake has been postulated to impair voltagegated calcium ion channels, calcium stores in the sarcoplasmic reticulum, and affinity of calcium to troponin C (1). • Beta-blocker and calcium-channel blocker use has been associated with an increased incidence of PEA and a concomitant decrease in ventricular fibrillation. The etiology has been attributed to their negative inotropic effects (2). PREVENTATIVE MEASURES

Avoidance of the “H’s” and “T’s” of PEA

PREOPERATIVE ASSESSMENT • The history should provide information regarding possible etiologies (drug overdose,

diabetes, coronary artery disease, trauma, intubation, insertion of central venous catheter, etc.) • Physical examination should include a palpation for a pulse, temperature, assessment for tracheal shifting, breath sounds, distended jugular veins. • Diagnostic procedures/Other – Blood sugar – Potassium level – Arterial blood gas – Echocardiogram to assess for cardiac tamponade, hypovolemia – Handheld Doppler to rule out pseudo-PEA • Monitors – Pulse oximetry, BP cuff, and arterial line indicate the lack of a pulse or mechanical contraction. – Tachycardia and hypertension often precede onset; however, perioperatively, this lacks specificity (surgical stimulation, light anesthesia, ephedrine, etc.). – EKG can demonstrate suggestive etiologies prior to the onset of PEA (usually applicable for intraoperative events). Peaked T waves: Consider hyperkalemia Inverted T waves (U waves): Consider hypokalemia ST segment changes: Consider cardiac thrombosis (myocardial infarction) Wide QRS: Consider myocardial injury, hyperkalemia, hypoxia Wide QRS and slow: Consider drug overdose from tricyclic antidepressants, betablockers, calcium-channel blockers Narrow QRS: Consider hypovolemia, pulmonary embolus, cardiac tamponade

DIFFERENTIAL DIAGNOSIS

• Pseudo-PEA • Implantable pacemaker firing in asystole

TREATMENT • ACLS for PEA. – The goal during resuscitation is to maintain perfusion to vital organs during cardiac arrest and simultaneously diagnose and treat any underlying causes until return of spontaneous circulation (ROSC) occurs. • In the operating room, begin CPR, administer or increase oxygen delivery, attach defibrillator. • PEA is not a shockable rhythm; therefore its algorithm differs from that of ventricular fibrillation and tachycardia (3). – Perform chest compression and ventilation for 2 minutes. The provider performing chest compressions should switch every 2 minutes. – Administer epinephrine (1 mg IV every 3–5 minutes) or vasopressin (40 U IV) to replace the first or second dose of epinephrine. – Note that atropine is no longer recommended for routine use in PEA/asystole.

– Check for shockable rhythm after 2 minutes. – If shockable, follow the appropriate algorithm – If not shockable, check for pulse. If pulse is present, begin post-resuscitation care. If absent, continue chest compressions and rhythm evaluation. • Airway management should also be addressed during the ACLS algorithm. – In the perioperative setting, the patient’s airway may already be secured; proper placement should be confirmed. – If the patient is undergoing monitored anesthetic care (MAC), mask ventilation or intubation should be performed – In the scenario where a supraglottic device is being utilized, consider converting to an endotracheal tube to provide positive pressure ventilation if appropriate. – The key is to minimize interruptions in chest compressions during airway placement. • Differential diagnosis: While performing CPR, providers should review the potentially reversible “H’s” and “T’s” as possible causes and correct them when possible (4). – Hypoxia should be treated with oxygen at a FiO2 100%.

– Hyperkalemia can be treated with a combination of calcium, bicarbonate, glucose, and insulin to stabilize myocardial cells and shift potassium intracellularly. Administer furosemide to enhance potassium excretion. – Hydrogen ion excess (acidemia) may be treated with IV bicarbonate and hyperventilation. – Hypovolemia can be corrected with IV fluid hydration or blood transfusion in cases of severe hemorrhage. – Hypothermia can be corrected with active internal warming techniques. – Tamponade can be treated with thoracotomy in cases of trauma or pericardiocentesis guided by echocardiography when possible. – Tension pneumothorax should be treated with needle decompression and chest tube placement. – Thrombosis, coronary: Thrombolytic therapy, coronary reperfusion, and emergency cardiopulmonary bypass should be considered. – Thrombosis, pulmonary: Consider fibrinolytic therapy when pulmonary infarction is suspected or known. – Toxins: Activated charcoal is indicated in many instances of drug overdose. Some toxins require specific correctional measures but ACLS guidelines should always be followed. Urgent toxicology consultation is recommended when ROSC occurs, if there are no other obvious causes. – Trauma involving the head and neck requires C-spine stabilization. The jaw-thrust maneuver should be used to establish an airway.

FOLLOW-UP • Intraoperative arrests with ROSC: The decision to proceed with the surgery depends on whether the initiating event has been resolved (or will recur) and the level of urgency/emergency of the procedure. Postoperatively, patients should be admitted to an intensive care unit for surveillance and ongoing therapy as indicated. • Out of OR arrests with ROSC: Patients should be transferred to an intensive care unit for

further stabilization and ongoing treatment, as indicated. Unresponsive patients should be considered for transfer to a facility that can provide a comprehensive care plan that includes rigorous cardiac, neurologic, and metabolic monitoring (5). • Avoid hyperventilation. Hyperventilation also increases intrathoracic pressure and inversely lowers cardiac output (5). • Induced hypothermia may be considered for neural and visceral protection • Coronary angiography and PCI are indicated when necessary and may be helpful even in comatose patients who do not show signs of ST segment elevation on ECG (5).

REFERENCES

1. arabee TM, Paradis NA, Bartsch J, et al. A swine model of pseudo-pulseless electrical activity induced by partial asphyxiation. Resuscitation. 2008;78(20):196–199.

2. oungquist ST, Kaji AH, Niemann JT. Beta-blocker use and the changing epidemiology of out-of-hospital cardiac arrest rhythms. Resuscitation. 2008;288:3308–3013. 3. Neumar RW, Otto CW, Link MS, et al. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122(18 suppl 3):S729–S767.Paradis NA, Halperin HR, Kem K. Cardiac arrest: The science and practice of resuscitation medicine. Cambridge University Press.Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: Postcardiac arrest care: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122(18 suppl 3):S768– S786.ACLS algorithmDesbiens NA: Simplifying the diagnosis and management of pulseless electrical activity in adults: A qualitative review. Crit Care Med. 2008;36(2):391–396 • Vanden Hoek TL, Morrison LJ, Shuster M, et al. Part 12: Cardiac arrest in special situations: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122(18 suppl 3):S829–S861.

See Also (Topic, Algorithm, Electronic Media Element) • Hyperkalemia • Cardiac tamponade • Pneumothorax • Pulmonary embolism • Hypothermia • ACLS anesthesia management

CODES ICD9 427.5 Cardiac arrest ICD10 • I46.9 Cardiac arrest, cause unspecified • I46.8 Cardiac arrest due to other underlying condition

CLINICAL PEARLS

• PEA refers to a heterogenous group of cardiac rhythm disorders; all characterized by pulselessness in the presence of some types of electrical activity other than VT or VF. • Treatment involves institution of the ACLS algorithm with concurrent diagnosis and treatment of the inciting cause. • Although the causes vary greatly, there appears to be a shared pathophysiologic cascade. Following an initial global myocardial ischemic event, hypoxia, acidosis, and increased vagal tone ensue. The pathogenesis is not completely understood at this time; however, there appears to be a renewed interest, given the increased incidence of PEA in cardiac arrests. A greater understanding may improve therapy and prognosis.

PYLORIC STENOSIS Jinlei Li, MD, PhD

BASICS DESCRIPTION

• Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis (IHPS), is the most common cause of intestinal obstruction in infants. It typically presents in infants between the ages of 5 days to 5 months, with the average age being 3 weeks. • Intractable, non-bilious projectile vomiting of ingested food is characteristic. • The classic/traditional treatment is an open pyloromyotomy via a Ramstedt RUQ transverse incision. More recently, circumumbilical laparoscopic approaches have supplanted the open repair, with cosmetic benefits and lower rates of wound infections (1,2). EPIDEMIOLOGY Prevalence

In the US: 3:1,000 infants Prevalence

More common in those of Northern European descent, less common in Africans, and rare in Asians Morbidity

• Dehydration • Metabolic derangements • Aspiration pneumonia

Mortality Rare

ETIOLOGY/RISK FACTORS

• Male to female infant ratio 4:1 • First born • Caucasians • Macrolide antibiotics (oral erythromycin) • Etiology unknown and probably multifactorial

PHYSIOLOGY/PATHOPHYSIOLOGY

• A hypertrophied pyloric sphincter muscle in the newborn causes functional obstruction and blocks the passage of stomach contents into the small intestine. • Contents of the small intestine do not reflux back into the stomach; thus bile is not present in the vomitus unlike other GI tract obstructions that occur below the pylorus.

• Gastric acid is comprised of 0.5% hydrochloric acid (HCl), and large quantities of potassium chloride (KCl) and sodium chloride (NaCl). Thus vomiting depletes sodium, potassium, chloride, and hydrogen ions. This results in a hypochloremic, hypokalemic metabolic alkalosis. • Initially, chloride ion loss inhibits the excretion of bicarbonate in the kidneys (to maintain electroneutrality) with a resultant metabolic alkalosis. In severe dehydration, the renin– angiotensin–aldosterone system is activated by hypovolemia. Hyperaldosteronism leads to retention of sodium and paradoxic excretion of potassium and hydrogen ions resulting in aciduria. In the body’s effort to maintain physiologic pH, a compensatory respiratory acidosis and hypoventilation ensue.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Pyloric stenosis is a medical, not surgical, emergency. Optimize fluid status, correct acid– base disturbances and electrolyte derangements prior to surgery. • Assume that the patient is a “full stomach”; a rapid sequence induction or awake intubation should be performed after gastric suctioning in the supine, lateral, and prone positions (3).

PREOPERATIVE ASSESSMENT SYMPTOMS

• Projectile non-bilious vomitus, belching, abdominal pain • Constant hunger, failure to thrive • Dehydration, manifested by depressed fontanelles, dry mucous membranes, or poor skin turgor

History

Age: Typically diagnosed between 3 weeks and 6 months of age. Signs/Physical Exam

• Palpation of an olive-sized mass in the right epigastric region. • Indirect hyperbilirubinemia and jaundice may exist in a small group of patients, possibly due to starvation. These typically resolve after surgery.

TREATMENT HISTORY

• The patient should remain NPO • IV fluids: Initial resuscitation in dehydrated patients should start with a 0.9% NaCl bolus of 20 mL/kg. Patients with normal laboratory values should have 1.5–2 times maintenance rates of a fluid such as 5% dextrose in water (D5W) or 0.25–0.45% NaCl. • Since lactate is metabolized to bicarbonate, lactated Ringer’s should be avoided. • Electrolyte replacement: Potassium can be added to fluid as needed after urine output is normalized. • A nasogastric tube may be placed prior to surgery to suction the stomach and prevent (or reduce) aspiration.

MEDICATIONS

• H2-blockers and antacids have not traditionally been used, as patients are routinely kept NPO as well as suctioned orally or nasally both preoperatively and prior to extubation. • Bicarbonate, in general, is not indicated even in patients with metabolic acidosis. The acid– base imbalance is the direct result of severe dehydration and hypoperfusion and therefore efforts should be directed to correct the underlying pathology. • Limited data is available for nonsurgical treatment. There is some evidence that IV or oral atropine can cause regression or decreased severity of obstruction. However, surgical correction is the standard of care and medical management should only be considered if the patient is a poor surgical candidate or whose parents are opposed to surgery (4).

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Generally accepted values for surgical readiness: – Serum [Cl-] <100 mEq/L – Serum [HCO3-] <28 mEq/L

– Urine output 0.5–1 mL/kg/hr • Ultrasound, has a 95% sensitivity and 100% specificity; it has largely replaced the historical oral contrast barium swallow test as the standard diagnostic tool CONCOMITANT ORGAN DYSFUNCTION Rare

CIRCUMSTANCES/CONDITIONS TO DELAY

Correction of volume deficit and electrolyte disturbances with IV fluids must be done prior to surgical repair. This can usually be accomplished in 24–48 hours.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Premedication with narcotics and benzodiazepines are generally avoided to prevent hypoventilation (respiratory acidosis) in the setting of metabolic alkalosis. • Atropine is routinely administered prior to gastric suction tube placement and succinylcholine injection to prevent bradycardia. Infants have stiff ventricles and are dependent on their heart rate to maintain adequate cardiac output; thus, bradycardia is poorly tolerated.

Special Concerns for Informed Consent Risk of pulmonary aspiration INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia with an endotracheal tube Monitors

• Standard ASA monitors • One IV catheter is adequate (22 gauge) • Invasive monitors such as arterial lines are generally not indicated in a fluid-resuscitated patient without other comorbidities.

Induction/Airway Management

• Patients may present with a nasogastric tube. If not, gastric contents should be removed with an orogastric tube prior to induction. Several passes in different positions may be necessary. • A rapid sequence IV induction with cricoid pressure is traditionally performed to reduce the risk for aspiration. • An awake intubation is indicated if there are concerns for a difficult airway or high risk for aspiration. Viscous lidocaine can be used to topicalize the oropharynx. • Although succinylcholine is generally contraindicated in children, it may be considered in pyloric stenosis surgery; atropine is administered to prevent bradycardia. When succinylcholine is contraindicated, intubation without muscle relaxant or with rocuronium can be performed. • Propofol and pentothal have been successfully used. Etomidate can result in adrenal suppression. • The choice of ETT size should be based on the baby’s age and weight. In this patient population, a cuffed or uncuffed 3.5–4.5 ETT is usually appropriate. A size 3.5 cuffed or uncuffed tube can typically be used. Although uncuffed tubes are routinely utilized to avoid subglottic stenosis, in this clinical scenario, cuffed tubes are appropriate (5).

Maintenance

• Inhalational agents or IV technique. • Narcotics should be used cautiously, if at all, secondary to existing metabolic alkalosis and subsequent ventilatory suppression. The surgical team routinely infiltrates the wound with local anesthetics at the end of the procedure. Acetaminophen is usually sufficient for postoperative pain control. • Oxygen should be minimized as tolerated to avoid oxygen toxicity and retinopathy of prematurity, especially in preterm patients. Nitrous oxide is generally avoided in laparoscopic procedures, at least during insufflation. • In laparoscopic surgery, there may be hypercapnia secondary to CO2 absorption.

Hyperventilation should be avoided to prevent apnea. Abdominal insufflation can result in decreased venous return, reduced functional residual capacity, and increased airway pressure; this should be anticipated and treated accordingly. • Normothermia should be maintained. Infants have a relatively larger body surface area from which heat can radiate to the cooler environment. In addition, temperature regulatory mechanisms have not fully developed. Severe hypothermia can lead to metabolic acidosis and coagulopathy.

Extubation/Emergence

• Awake extubation is recommended, given the risk of aspiration, hypoventilation, and apnea. • If a non-depolarizing muscle relaxant has been used, check twitch monitor and adequately dose reversal agents as appropriate. • Stomach and oral secretions should be thoroughly cleared prior to extubation.

FOLLOW-UP BED ACUITY

Regular floor bed; observation for 12 hours is needed to assess for postoperative apnea and hypoventilation. MEDICATIONS/LAB STUDIES/CONSULTS

This age group is prone to hypoglycemia and glucose levels should be checked especially when dextrose-containing maintenance fluids are ceased. COMPLICATIONS

• Duodenal perforation • Incomplete myotomy with recurrent vomiting • Dehiscence • Hernia

REFERENCES

1. Bissonnette B, Sullivan PJ. Pyloric stenosis. Can J Anesth. 1991;38(5):668–676.

2. Hulka F, Harrison MW, Campbell TJ, et al. Complications of pyloromyotomy for infantile hypertrophic pyloric stenosis. Am J Surg. 1997;173:450–452. 3. Cook-Sather SD, Tulloch HV, Cnaan A, et al. A comparison of awake versus paralyzed tracheal intubation for infants with pyloric stenosis. Anesth Analges. 1998;86:945–951. 4. Yamataka A, Tsukada K, Yokoyama-Laws Y, et al. Pyloromyotomy versus atropine sulfate for infantile hypertrophic pyloric stenosis. J pediatr surg. 2000;35(2):338–342. 5. Lichtor JL, Shiveley TJ, Wallace EC. Images in anesthesiology: pyloric stenosis. Anesthesiology.. 2010;112:1270.

ADDITIONAL READING

• Malhotra V, Sharma A. Pyloric Stenosis. In: Yao FF, ed. Yao and Artusio’s anesthesiology problem-oriented patient management. 6th edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:514–526.

See Also (Topic, Algorithm, Electronic Media Element) • Alkalosis metabolic • Hypokalemia • Hypoglycemia

CODES ICD9

• 537.0 Acquired hypertrophic pyloric stenosis • 750.5 Congenital hypertrophic pyloric stenosis ICD10

• K31.1 Adult hypertrophic pyloric stenosis • Q40.0 Congenital hypertrophic pyloric stenosis

CLINICAL PEARLS

• Pyloric stenosis is a medical, not surgical, emergency. Fluid and electrolyte abnormalities should be optimized prior to surgical repair. • Patients are considered to have a “full stomach” and require gastric decompression followed by a rapid sequence induction or awake fiberoptic intubation. • Judicious use of respiratory depressants such as narcotics and benzodiazepines. • Postoperative hypoventilation or apnea can occur with intraoperative hyperventilation or an alkalotic CSF.

QT PROLONGATION

Marc A. Logarta, MD, DABA, FANZCA

BASICS DESCRIPTION

• The QT interval (QT) refers to the time between the start of ventricular depolarization to the end of repolarization; normally between 0.3 and 0.44 seconds. • A prolonged QT interval is affiliated with ventricular arrhythmias, particularly the development of Torsades de Pointes. This condition is otherwise known as long QT syndrome (LQTS) and can be either congenital or “acquired.” • Surgical stimulation and several perioperative medications can have adverse effects on patients with LQTS. EPIDEMIOLOGY Prevalence

US: 1:1,100–5,000 people Morbidity

Although some patients present initially with syncope to the emergency department, for many patients there is no pre-morbid state prior to collapse and out-of-hospital cardiac arrest. Mortality

US: 4,000/year Risk Factors

• Increased sympathetic tone can precipitate Torsades de Pointes. • Electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia) • Drugs (see Table 1) • Anorexia nervosa (severe starvation) • Subarachnoid hemorrhage • Hypothermia Table 1 Medications that affect the QT interval PHYSIOLOGY/PATHOPHYSIOLOGY

• Normal ventricular depolarization: After the sinoatrial (SA) node spontaneously depolarizes (sodium channel influx), the signal is spread via 3 accessory conduction tracts in the atrium to the atrioventricular (AV) node. Adjacent myocardial cells depolarize in a domino fashion. Electrical depolarization is followed by mechanical contraction of the atrium, with blood being pumped into the ventricles. The conduction fibers from the atrium are connected to those in the ventricle via the bundle of His (preceded by the AV node); in the ventricles, the signal is then transmitted along the left and right bundle branches onto the Purkinje fibers.

In the same manner, the adjacent muscle cells are depolarized in a domino fashion, and depolarization is followed by ventricular contraction and blood ejection. • Normal early myocardial repolarization in the ventricle begins with a rapid, transient efflux of potassium. Potassium efflux continues via slowly activating (iKs) and rapidly activating (iKr) delayed rectifier channels. However, this process is counteracted by an influx of calcium and sodium that prolongs repolarization and allows time for mechanical contraction and systolic ejection of blood. The complex interactions between these ions and their respective channels dictate the duration and characteristics of repolarization. • Heterogenous rate of repolarization: The rate of repolarization is not equal between the epicardium, mid-myocardium, and endocardium. The mid-myocardial cells have less iKs channels and more iNa channels; therefore, the rate of repolarization is slower than the other 2 layers. This causes a transmural dispersion of repolarization (TDR). – EKG: The peak of the T wave represents epicardial cell repolarization and the end of the T wave represents mid-myocardial cell repolarization (where repolarizatoin is slowest). – TDR is manifested on the EKG by the interval between the peak of the T wave to the end of the T wave (Tp-e). • The QT interval represents the time period during which ventricular depolarization and repolarization occur. It is rate-dependent; bradycardia has longer intervals whereas tachycardia has shorter intervals. Thus, its assessment and interpretation must factor in, and be corrected for, heart rate. The corrected QT (QTc) is calculated using Bazett’s formula, QTc = [QT/(R–R)]. R−R is the R-to-R interval in seconds. • LQTS is caused by the malfunction of cardiac ion channels. Any condition that qualitatively or quantitatively decreases the iK channel function or increases the iNa channel function will prolong the QT interval, exaggerate the TDR, and prolong repolarization. This heterogeneity of repolarization leads to an increased potential for self-sustaining re-entrant circuits and early after-depolarizations (EADs), which can degenerate into Torsades de Pointes. – Prolonged QT is defined as a corrected QT interval (QTc) >0.45–0.47 seconds in males and 0.47–0.48 seconds in females. • “Acquired” LQTS is thought to occur in silent gene carriers until symptoms manifest after being exposed to a provoking drug or sympathetic stimulation.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperative assessment of the patient may reveal historical and/or ECG characteristics diagnostic for LQTS. It is necessary to correct for heart rate; most modern EKG machines provide a QTc value. • Anesthesia in patients with untreated LQTS carries a very high risk for malignant ventricular arrhythmias. They should be optimized prior to surgery and should be on a maintenance beta-blocker regimen. • Avoidance of sympathetic outflow is necessary as this predisposes to re-entrant ventricular arrhythmias and Torsades de Pointes.

PREOPERATIVE ASSESSMENT SYMPTOMS

• 60% of patients are asymptomatic until a presenting syncopal or pseudoseizure episode (usually in childhood or early adulthood). • Occasionally, the first symptom may present as Torsades de Pointes under anesthesia.

History

• In patients without known LQTS, some “red flags” to watch out for are syncope with or without stress, unexplained sudden cardiac death before age 30 in immediate family members, and family members with known LQTS. It will often manifest as a child or in early adulthood. If concern for LQTS is raised in an elective case, referral to a cardiologist should be made for a possible electrophysiology study. • Patients with a known history of LQTS should be on scheduled beta-blockers that are continued perioperatively. Serum electrolytes should be within normal limits. Signs/Physical Exam

• Often nonspecific physical examination • Adequately beta-blocked patients should (ideally) not have any change in QT interval during a Valsalva maneuver. MEDICATIONS

Beta-blockers help reduce the incidence of cardiac events, but they are not entirely effective for preventing sudden death. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• ECG: Prolonged QTc, T wave alternans, notched T wave in 3 leads • Serum electrolytes should be assessed and abnormalities should be corrected. • If a pacemaker or ICD is present, follow appropriate perioperative management.

CONCOMITANT ORGAN DYSFUNCTION

• In Jervell and Lange-Nielsen syndrome, patients also have congenital deafness. • In Andersen syndrome (LQT7), patients have periodic paralysis.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Inadequate beta-blockade • Abnormalities in electrolytes can delay repolarization (hypokalemia, hypomagnesemia, and hypocalcemia). CLASSIFICATIONS

• Acquired LQTS: It is now thought that these cases have common nucleotide polymorphisms that alter ion channel repolarization behavior in the presence of drugs, electrolyte abnormalities, or in certain disease states. • Congenital LQTS: 8 different genotypes (LQT1-8) have been identified. Romano–Ward syndrome is the most common presentation of congenital LQTS and is inherited in an autosomal dominant manner. Jervell and Lange-Nielsen syndrome is autosomal recessive and is associated with deafness.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Consider preoperative sedation when appropriate. Limiting anxiety and sympathetic outflow is crucial. • Avoid abrupt and loud noises; may trigger Torsades de Pointes.

INTRAOPERATIVE CARE Choice of Anesthesia

Epidurals, spinals, and general anesthetics have all been administered safely; there is no evidence that one mode is safer than the other. Monitors

• Low threshold for intra-arterial monitoring • Low threshold for central venous access, as it can facilitate transvenous pacing.

Induction/Airway Management

• Midazolam, fentanyl, morphine, and propofol appear to be benign in LQTS. Thiopental prolongs the QT interval but may reduce dispersion of depolarization and has been safely used in congenital LQTS. Ketamine should be avoided. • Succinylcholine may prolong the QT interval. • Laryngoscopy, intubation, suctioning, and cold-inspired gases can cause a sympathetic outflow; these potent stimuli may be attenuated by a short-acting opioid and/or esmolol. • Consider topical anesthesia to vocal cords prior to intubation. • Total IV anesthesia with a propofol and remifentanil infusion may provide excellent attenuation of sympathetic outflow throughout induction, intraoperative maintenance, and emergence; with the advantage of a short context sensitive half-life. Maintenance

• Avoid sympathetic stimulation by maintaining normocarbia, normothermia, normoglycemia, normovolemia, and normoxia. • Volatile anesthetics prolong the QT interval, but isoflurane and sevoflurane have been used safely in congenital LQTS. • Keep patient “deep” or adequately anesthetized; otherwise innocuous stimuli can result in increased sympathetic outflow. • High ventilatory pressures should be avoided as this may cause QT prolongation. • Pancuronium has vagolytic properties and should be avoided. • Avoid sympathomimetic drugs such as ephedrine. • Droperidol should be avoided in LQTS. Ondansetron is considered a medication with possible risk for prolonging the QT interval. Extubation/Emergence

• Consider “deep” extubation while the patient is in a surgical plane of anesthesia, if

appropriate. • Neostigmine, edrophonium, atropine, and glycopyrrolate should be avoided because each may cause QT interval prolongation.

FOLLOW-UP BED ACUITY

• Will need postoperative ECG monitoring, as the perioperative period may exacerbate QT prolongation. • Good pain control can avoid sympathetic stimulation.

COMPLICATIONS

• Torsades de Pointes: – Some episodes will be short and self terminating. – Can occur at any point in the perioperative period. – Can manifest in hemodynamic instability and degenerate into ventricular fibrillation. • Treatment consists of: – If unstable, ACLS should be instituted immediately with early chest compressions, asynchronous defibrillation, and magnesium sulfate (30 mg/kg). – Magnesium dose can be repeated after 15 minutes, followed by an infusion of 3–20 mg/min if arrhythmias persist. – If resistant to magnesium, Torsades can be treated with pacing to accelerate the heart rate.

REFERENCES

1. Kies SJ, Pabelick CM, Hurley HA, et al. Anesthesia for patients with congenital long QT syndrome. Anesthesiology. 2005;102:204–210. 2. Hunter J, Sharma P, Rathi S. Long QT syndrome. Continuing education in anaesthesia. Critical Care and Pain. 2008;8(2):67–70. 3. Schwartz PJ, Moss AJ, Vincent GM. Diagnostic criteria for the long QT syndrome: An update. Circulation. 1993;88:782–784.

ADDITIONAL READING • www.torsades.org

See Also (Topic, Algorithm, Electronic Media Element) • ACLS anesthetic management • 12-lead EKG • Ventricular fibrillation • Magnesium • Defibrillation

CODES

ICD9

• 426.82 Long QT syndrome • 794.31 Nonspecific abnormal electrocardiogram [ECG] [EKG] ICD10

I45.81 Long QT syndrome

CLINICAL PEARLS

• LQTS is a significant cause of sudden death in young people, and is probably underdiagnosed. • For a significant number of patients with LQTS, their first manifestation may be under anesthesia. • Avoid stimuli that evoke sympathetic outflow including hypothermia, pain, hypoxia, excessive ventilatory pressure, and hypovolemia. • For patients with known LQTS, ensure that they are not hypokalemic, hypocalcemic, or hypomagnesemic. Ensure that they are adequately beta blocked.

RADIATION SAFETY Russell K. McAllister, MD Bradley T. Dollar, MD

BASICS DESCRIPTION

• Medical exposure to irradiation typically comes from three major sources: Diagnostic radiologic examinations, the use of radiopharmaceuticals in nuclear medicine, and therapeutic applications of radiation. We will focus on radiologic examinations. • Anesthesia providers are exposed to increasing amounts of radiation as the intraoperative use of fluoroscopy and other radiologic techniques increase. • Anesthesiology pain practitioners increasingly use fluoroscopy to facilitate proper needle placement for nerve blocks. • Perspective: Radiation exposure occurs daily in the form of cosmic rays from outer space (higher during airplane travel) and naturally occurring radioactive materials (e.g., radon gas). Persons living at higher altitude or at the north and south poles have higher exposure to cosmic radiation than persons at sea level or nearer the equator. PHYSIOLOGY PRINCIPLES

• Factors affecting the dose of radiation with x-ray include patient size, beam angle, type of fluoroscopy, and acquisitions. • Patient size: – Radiation is attenuated by 1/2 for every 5 cm of soft tissue. For example, a patient with 10 cm of extra tissue requires four times the dose to maintain the same image quality. – Dose increases in a fluoroscopy unit are automatically controlled so the operators do not perceive these differences. • Beam angle: – Directing the beam through the patient at an oblique angle will raise the radiation dose due to increased tissue thickness. • Type of fluoroscopy: – Continuous fluoroscopy allows real time visualization of dynamic activity using low x-ray tube currents. – Pulse fluoroscopy acquires frames that are less than real time (e.g., 7.5 or 15 frames per second) thereby reducing patient dose. – Pulsed – High (30 f/s) approaches continuous dose rate. – Photospot images (e.g., acquisitions) are obtained utilizing the same imaging chain as fluoroscopy but the x-ray tube current increases from 1 to 5 mA to ∼300 mA. Photospot images are of diagnostic quality required for most clinical diagnosis. • Increased magnifications: – Dose increased in order to maintain image brightness – Not a substantial effect on patient or operator.

• Collimation: The process of restriction and confinement of an x-ray beam to focus only on the area of interest. – Decreases area of skin and volume of tissue exposed and makes it easier to distribute the skin dose – Less scatter to personnel – Improved image quality from less scatter – Increases automatic brightness control that increases entrant skin dose

ANATOMY

• Tissue weighting factors refer to the different probabilities for the occurrence of stochastic radiation effects. Higher values reflect an increased probability of detrimental effects to that organ system from radiation exposure. See Table

• Additional anatomical considerations: – Eyes. Excessive exposure can lead to premature cataracts (left eye most common for c-arm operators due to usual location of beam). – Developing fetus during pregnancy can be affected (especially during organogenesis in the first trimester). – Patient skin. Varying the entry point of the radiation beam, when practical, will spread the radiation over more skin and reduce the likelihood that any one area will be overexposed. The image intensifier should be lowered as close as practical to the patient’s skin to minimize scatter and maximize the gap between the x-ray tube and the skin. Even for a fixed fluoroscopy unit (tube fixed under the unit’s table so that the tube to skin distance is fixed) lowering the image Intensifier will lower the skin dose.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Cells that survive radiation exposure may be subsequently modified. This can occur as carcinogenenesis or hereditary effects, both of which are stochastic effects. • Stochastic effects (cancer and genetic damage) have an increased risk of occurrence with increased radiation dose; they occur many years after exposure. There is no threshold or certainty that they will occur, only an increased risk (stochastic effects are also known as the “linear-no threshold theory”). Furthermore, the severity of that disease is independent of the dose once the disease is present. • Nonstochastic effects (deterministic effects). Unlike stochastic effects, they have a clear relationship between the exposure and the effect. Nonstochastic effects often result from very large dosages in a short period of time and manifest within hours or days. Examples include erythema, skin and tissue burns, sterility, and radiation sickness. • Genetic mutations leading to hereditary effects. Any dose of radiation has the potential to cause a mutation in the DNA that can be passed on genetically. Females are born with all of the eggs that they will have for their lifetime. Proper shielding should occur to minimize the risk. • Early effects of ionizing radiation. These are dose-dependent stochastic effects of total body radiation that occur in the following sequence: – Hematologic (bone marrow syndrome)

– GI syndrome – CNS syndrome (highest doses of exposure). – Local tissue damage (skin, gonads, extremities) – Hematologic depression – Cytogenic damage • Late effects: – Leukemia – Malignancies (bone, lung, breast, etc.) – Local tissue damage (skin, gonads, eyes) – Shortened life span – Genetically significant dose • Effects on fetus: – Lethal effects can occur before or immediately after implantation of the fertilized ovum in the uterine wall or at any time during intrauterine development. It can be expressed as prenatal or neonatal death. – Congenital malformation is expressed after birth as a result of radiation exposure during organogenesis (multiple organ systems may be affected, but is most commonly seen in the CNS, skeletal, and ocular systems). – Childhood malignancies (leukemia) – Diminished growth and development (intrauterine or after birth) – Atomic bomb survivors exposed in utero most commonly presented with microcephaly and mental retardation defects. PERIOPERATIVE RELEVANCE

• Radiation reduction can be accomplished by – Reducing the gap between the patient and the image intensifier (less scatter) – Minimizing beam time – Collimating (with fluoro OFF) – Using the lowest possible fluoro pulse rate (high-dose settings deliver 10 times the dose). – Minimizing acquisition (use last image hold and cine hold). – Using lowest frame rate acquisition as needed (and variable frame rate). – Changing beam angle to vary skin dose to avoid patient skin burns (collimation helps). – Using the least magnification possible. – Positioning the C arm fluoroscopy field of view on the opposite side of the practitioner (reduces the exposure of the upper body). – During cross table x-rays, if the image intensifier side is positioned over the patient, dosing can be reduced by 1/5th (scatter occurs as the beam contacts the patient). • Reducing provider dose: – Lead apron. During fluoroscopy, a 0.5 mm lead equivalent apron can attenuate 95% of the scattered radiation to the shielded torso; a 0.25 mm apron attenuates 80%. Wear a wraparound apron if the back will be to the source. – Thyroid shield – Custom lead protective glasses: A 5 mm thick lens will block 92% of the radiation and a 10 mm thick lens will block 99%. Regular glass lenses of 5 and 10 mm thickness block 30% and 50% of radiation, respectively.

– Table skirt – Overhead shield – Lead gloves provide minimal protection and may cause a false sense of security – Holding hands with lead-lined gloves in x-ray beam causes fluoroscopy unit to adjust to increase the dose delivered (don’t place hands in primary beam). – Stand at least 6 feet from beam if possible. • Monitoring provider radiation dose: – Over apron dosimeter is placed at the thyroid collar to monitor exposure to eyes, thyroid, and head. – Under apron dosimeter to monitor exposure to the rest of the body. – For practitioners near the beam, a finger ring dosimeter to monitor exposure to hands. – Pregnant providers should be provided an additional dosimeter to be worn under the lead apron at waist level to monitor fetal exposure and should strongly consider a wrap around lead apron that provides coverage from exposure from behind. Usual precautions should be utilized as well. • Recommended dose limits. The International Commission on Radiological Protection recommends an effective dose limit of 20 mSv/year (mSv = millisievert) averaged over 5 years to limit the probability of stochastic effects. In addition, the effective dose should not exceed 50 mSv in any given year. Pregnant females should have a supplementary equivalent dose limit of 2 mSv applied to the surface of the abdomen to reduce the risk of fetal effects.

EQUATIONS

• Equivalent doses = sum of the weighted absorbed doses; does not take into account the differing susceptibilities of radiation to different organs. • Effective dose = sum of the weighted equivalent doses in all tissues and organs of the body. Accounts for the “tissue weighting factor” that represents the relative contribution of that organ to the total detriment due to those effects resulting from uniform radiation of the whole body. • Rule of thumb – One step back from tableside: Cuts exposure by a factor of 4.

GRAPHS/FIGURES

Radiation units – There are a number of units to measure radiation dose and exposure: • rad: Radiation absorbed dose • rem: Roentgen-equivalent-man • Roentgen (R, r) (rent-gen, rent-chen). • sievert (Sv) (see-vert). The most pertinent unit for measuring ionizing radiation effective dose, which accounts for relative sensitivities of different tissues and organs exposed to radiation. The radiation quantity measured by the sievert is called the effective dose. A mSv is one-thousandth of a sievert. • Comparative patient radiation doses of different studies: – Dental x-ray – 0.005 mSv – Chest x-ray – 0.1 mSv – Mammogram – 0.4 mSv – CT abdomen/pelvis – 15 mSv – CT abdomen/pelvis with and without contrast – 30 mSv

– Fluoroscopic-guided procedures – Difficult to measure due to operator variability and fluoroscopy time differences.

REFERENCES

1. Mettler FA, Upton AC. Medical Effects of Ionizing Radiation, 3rd ed. Philadelphia: WB Saunders Company, 2008.

2. Norris TG. Radiation safety in fluoroscopy. Radiol Technol. 2002;73(6):511–536. 3. Schueler BA, Vrieze TJ, Bjamason H, et al. An investigation of operator exposure in interventional radiology. RadioGraphics. 2006;26:1533–1541. 4. Seeram E. Radiation Protection. Philadelphia: Lippincott-Raven, 1997. 5. Tremains MR, Georgiadis GM, Dennis MJ. Radiation exposure with use of the inverted-carm technique in upper-extremity surgery. J Bone Joint Surg. 2011;83:674–678. See Also (Topic, Algorithm, Electronic Media Element) • Infectious disease exposure in the health care worker

CODES ICD9 990 Effects of radiation, unspecified ICD10 • T66.XXXA Radiation sickness, unspecified, initial encounter • T66.XXXD Radiation sickness, unspecified, subsequent encounter • T66.XXXS Radiation sickness, unspecified, sequela

CLINICAL PEARLS

• Minimizing provider exposure includes the use of shielding, increasing distance from the source of radiation, and reducing exposure time. • Ultrasound uses acoustic radiation and no known risk is associated with this type of imaging. • MRI. The patient and provider are exposed to rapidly changing magnetic fields as well as electromagnetic radiation. Although thought to be safe, there is a potential for undiscovered biological effects. Known hazards may occur in providers with pacemakers, defibrillators, or other implantable devices. In addition, ferrous materials in the vicinity can become hazardous projectiles. • Standard set-up for a C-arm is the x-ray tube in the down position (near the floor) and the image intensifier in the up position. These devices are occasionally inverted. It is important to recognize the configuration so that the practitioner is able to minimize provider exposure and also in order to properly shield the patient. • Lead aprons should be hung and not folded. Folding leads to cracks in the lead that can cause decreased effectiveness in the barrier.

• Routine maintenance of equipment should be performed to ensure proper functioning and safety. • X-rays done in patient settings that have multiple patients (postanesthesia care unit) should be avoided to minimize unnecessary exposure of other patients to radiation. • Anesthesia providers are occasionally asked to care for critically ill patients in the CT scanner. Recall that radiation doses for CT scans are much higher and the provider should maintain as many safety measures as possible (time, distance, and barriers). • There is significantly increased x-ray tube current to obtain a photo spot (acquisition) image: 1 photo spot image is approximately equivalent to 20–25 seconds of fluoroscopy time (though significant variation can exist secondary to technique).

RADICAL NECK DISSECTION Julie McSwain, MD, MPH Laura L. Roberts, MD

BASICS DESCRIPTION General

• Performed to remove primary and metastatic cancer from the head and neck. The close proximity of several structures, including lymph nodes in the neck, facilitates spread to nearby tissues. • Traditional radical neck dissection (RND) is defined as the exploration and systematic removal of lymph nodes from all five levels of the neck as well as an en bloc resection. – Neck levels describe and identify lymph nodes in the neck. Level I begins cephalad to the submental and submandibular triangles. Subsequent levels progress caudally down the neck with level 5 including the spinal accessory nerve and transverse cervical artery. – En bloc resection describes the removal of the sternocleidomastoid muscle, internal jugular (IJ) vein, and spinal accessory nerve (CNXI) contained within those neck levels (1)[C]. • Modified RND removes lymph nodes from all five levels but is “modified” to preserve the sternocleidomastoid muscle, IJ vein, and/or CN XI. Position

• Supine; often with a shoulder roll to improve neck extension and exposure • Head laterally rotated to opposite side of the surgery • Arms often tucked to allow surgeons to stand closely • Head of bed often rotated 180° from the anesthesia machine

Incision

Varies based on patient characteristics and surgeon preference (e.g., wine glass, apron access, McFee). Typically, a horizontal skin incision with vertical extension along the neck allows for good exposure. Approximate Time

Variable. Usually takes 2–4 hours but may take significantly longer if a free flap reconstruction is involved. Pathological evaluation of lymph nodes during surgery may increase anesthetic time with very little surgical stimulation to the patient. EBL Expected

• Typically 100–300 mL • Blood loss may be increased in patients who have received preoperative radiation therapy, require primary tumor resection in addition to lymphadenectomy, or require flap reconstruction.

• It may be prudent to type and screen all patients undergoing RND and crossmatch those with anemia or at an increased risk for blood loss.

Hospital Stay

2–5 days; recent evidence for <24-hour stay has been reported in patients who had no primary site resection and no oral resection (2)[B].

Special Equipment for Surgery

• Nerve monitoring via direct nerve stimulation for the spinal accessory nerve (CN XI), hypoglossal nerve (CN XII), and marginal mandibular branch of the facial nerve are common. The marginal mandibular branch of the facial nerve aids in smiling (supplies muscles of lower lip and chin); it is a small nerve and is at higher risk of injury. • Difficult airway equipment may be needed to secure the airway, including surgical tracheostomy equipment.

EPIDEMIOLOGY Prevalence

In the US, ∼ 5,000–10,000 neck dissections/year Prevalence

Dependent on primary cancer source (e.g., squamous cell, melanoma, thyroid, and salivary gland) Morbidity

Ranges from 3–30% and includes bleeding and infection. Risk increases based on the nature of dissection (radical, modified), ASA class, and duration of anesthesia (3)[B].

Mortality Low

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patient population often has a history of longstanding tobacco use with resultant cardiovascular and pulmonary comorbidities. • Airway management may be challenging given the location and amount of tumor burden in the neck as well as a previous history of radiation or surgery on the head or neck for primary tumor. • Nerve monitoring precludes the use of intermediate and long-acting muscle relaxants. • Fluid and hemodynamic management may be challenging if free flap reconstruction is employed; need to balance the maintenance of anesthesia, combined with low surgical stimulation and the need to avoid vasopressors (may jeopardize perfusion of the free flap).

PREOPERATIVE ASSESSMENT SYMPTOMS

• Common symptoms include dysphagia, odynophagia, and neck/jaw pain that can result in

weight loss and malnutrition. • Some patients may be asymptomatic and metastatic tumor is found on serial follow-up exam.

History

Carefully question the patient about previous anesthetics and history of past intubation attempts. Many patients have a history of previous head and neck surgery or radiation therapy to the neck, which can complicate airway management. Evaluation of old anesthetic records, if available, may be invaluable. Signs/Physical Exam

• Auscultation of the heart and lungs, at a minimum, is necessary for each patient. • Careful airway exam given the potential for a difficult airway (Mallampati score, mouth opening, thyromental distance, neck mobility, tracheal palpation, and cervical range of motion).

MEDICATIONS

• Chemotherapeutic agents • Bronchodilators, steroids • H2 blockers or proton pump inhibitors

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Type and screen is usually warranted for all patients. • Further preoperative lab testing is based on individual patient comorbidities. • Preoperative lymph node biopsies may be performed by the surgeon prior to RND. • Radiographic studies such as neck CT or head/neck MRI are often performed preoperatively to assess for involvement of nearby structures (e.g., vasculature). PET scan may be completed to evaluate for further metastatic disease. Anaesthetist may consider reviewing films to assess for tumor invasion or edema of the trachea. • Barium swallow may be performed preoperatively to evaluate patients at high risk for swallowing difficulty/malnutrition.

CONCOMITANT ORGAN DYSFUNCTION

• Cerebrovascular disease, coronary artery disease, and COPD are common if the patient is elderly and has a significant history of tobacco use. • Thyroid disease/dysfunction may be evident if the patient has a history of primary thyroid cancer.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Patient specific: Related to patient comorbidities (e.g., beta-blockers, albuterol, and

nonparticulate antacids) • Airway topicalization, anticholinergics, and anxiolytics may be necessary for patients requiring awake fiberoptic intubation.

Special Concerns for Informed Consent

Consent for anesthesia should include a discussion of special airway management (e.g., need for awake fiberoptic), the possibility of blood transfusion if the patient is at a higher risk for blood loss, the possibility of tracheostomy, and postoperative mechanical ventilation. Antibiotics/Common Organisms

• Broad spectrum, third-generation cephalosporin such as cefazolin can protect against skin flora. • Ampicillin/sulbactam if the surgery involves the parapharyngeal cavity or free flap reconstruction. • Clindamycin is a reasonable alternative for the penicillin-allergic patient.

INTRAOPERATIVE CARE Choice of Anesthesia

• Typically general anesthesia with an ETT • Consider a combination of regional anesthesia (superficial or deep cervical plexus blocks for postoperative pain management) and general anesthesia in select patient populations. Regional anesthesia as the sole anesthetic is limited by patient willingness, anaesthetist’s experience, surgical time, and surgical site involvement.

Monitors

• Two large bore IVs • Arterial line may be considered in patients with known heart dysfunction and moderate-tosevere lung dysfunction, or in patients undergoing concomitant free flap reconstruction. • Flow-volume loops for patients with moderate to severe lung dysfunction. • Central line is rarely required unless the patient has moderate-to-severe left ventricular dysfunction or poor existing IV access. CVC sites are typically limited to the contralateral IJ/subclavian (or femoral veins if the patient is undergoing bilateral RND). • Brain function monitors such as a BIS may be helpful if total IV anesthesia is employed or if muscle relaxants are avoided due to nerve monitoring.

Induction/Airway Management

• Special airway management should be considered based on the preoperative airway assessment, history of previous anesthetics, history of radiation therapy, recent radiographic studies, and discussion with surgical ENT colleagues to delineate potential difficulties with intubation. • If a standard IV general induction is to be performed, have difficult airway equipment and assistants readily available for a potential difficult airway. • Awake tracheostomy may be necessary if the airway is severely compromised. • If surgical nerve monitoring is planned, avoid intermediate and long-acting muscle relaxants to facilitate intubation.

Maintenance

• A balanced technique based on the anaesthetist’s preference, use of nerve monitoring, and length of procedure • Total intravenous anesthesia (TIVA). Propofol TIVA is usually well-tolerated by patients. It results in rapid emergence and has been shown to reduce postoperative nausea/vomiting; it may be combined with another sedative or opioid as part of a balanced technique. May see hypotension at general anesthetic doses; decreases in BP with propofol TIVA may be associated with decreased surgical blood loss. • Volatile agents. Easy to use, well tolerated by patients. • Narcotics. Free flap reconstruction may be associated with significant postoperative pain. However, opioids can result in sympatholysis and potential hypotension that is compounded during times of minimal surgical stimulation. Balance the titration or infusion of narcotics intraoperatively against the potential for hypotension, or consider starting titration toward the end of the procedure. • Free flap perfusion may be enhanced by the avoidance of vasopressors and keeping the patient warm. Vasoconstrictors may reduce flow; hypothermia results in vasoconstriction. • If surgical nerve monitoring used, avoid muscle relaxants. • IV and breathing circuit extensions may be necessary when the bed is turned

Extubation/Emergence

• Standard extubation criteria apply. Try to avoid coughing/bucking on the ETT; control BP during emergence to avoid bleeding from the wound. • Extubation in patients who were difficult to intubate, have undergone long procedures with free flap reconstruction and/or tracheostomy placement, or are at high risk for pharyngeal or laryngeal edema, should only be performed with extreme caution, if at all. Consider postoperative mechanical ventilation and intensive care unit (ICU) transport.

FOLLOW-UP BED ACUITY

For uncomplicated RND, a floor bed is usually adequate. ICU monitoring is often necessary for patients who have undergone free flap reconstruction and recent tracheostomy placement. ANALGESIA

• IV narcotics, including patient-controlled analgesia, are typical. • Superficial or deep cervical plexus nerve blocks may be considered in patients with chronic pain or other unique conditions.

COMPLICATIONS

• Intraoperative complications include – Hypotension/bradycardia due to carotid sinus irritation – Prolonged QT interval due to interruption of the cervical sympathetic innervation of the heart in patients undergoing right RND – Air embolism if the IJ is opened or sacrificed

– Airway trauma/edema due to a difficult airway or prolonged intubation – Pneumothorax if dissection is low in the neck – Massive hemorrhage and/or stroke if the carotid is injured (4)[C]. • Postoperative complications include – Hypertension due to carotid sinus denervation (5)[B] – Airway compromise due to tight dressing/possible hematoma or postoperative oropharyngeal/laryngeal edema – Diaphragm dysfunction if the phrenic nerve is injured – Facial edema if the IJ is sacrificed – Winged scapula and shoulder dysfunction if the spinal accessory nerve is sacrificed – Facial droop if the facial nerve is injured – Carotid blow-out (rare but carries 50% mortality) (4)[C]. • Preoperative malnutrition and history of neck radiation increases the risk of a postoperative wound infection and poor wound healing.

PROGNOSIS

Overall good, but ultimately based on the type and extent of metastatic disease and the ability to completely resect disease burden.

REFERENCES

1. obbins KT, Shaha AR, Medina JE, et al.Consensus statement on the classification and terminology of neck dissection. Arch Otolaryngol Head Neck Surg. 2008;134(5):536–538. 2. Tracy JC, Spiro JD. Short hospital stay following neck dissection. Arch Otolaryngol Head Neck Surg. 2010;136(8):773–776. 3. Ferrier MB, Spuesens EB, Le Cessie S, et al. Comorbidity as a major risk factor for mortality and complications in head and neck surgery. Arch Otolaryngol Head Neck Surg. 2005;131:27–32. 4. Kerawala CJ, Heliotos M. Prevention of complications in neck dissection. Head Neck Oncol. 2009;12:1–35. 5. Celikkaat S, Akyol MU, Koc C, et al. Postoperative hypertension after radical neck dissection. Otolaryngol Head Neck Surg. 1997;117:91–92.

ADDITIONAL READING

• Lalwani AK. Current Diagnosis and Treatment in Otolaryngology: Head and Neck Surgery. McGraw-Hill Medical, USA, 2008.

See Also (Topic, Algorithm, Electronic Media Element) • Tracheostomy • Cervical block • Carotid sinus

CLINICAL PEARLS

• RND is a common surgical procedure for cervical metastasis from head and neck cancer. • Most patients now undergo a modified version of the classical RND that allows sparing of important vascular and nervous structures and in turn reduces overall morbidity and mortality. • GETA is usually employed intraoperatively; be prepared for a potential difficult airway. • Nerve monitoring may prohibit the use of neuromuscular blockers. • Damage to major vascular structures in the neck is rare but potentially life-threatening.

RAYNAUD’S PHENOMENON Edward Kosik, DO

BASICS DESCRIPTION

• Raynaud’s phenomenon (RP) is an exaggerated and reversible vasospasm of digital arteries in response to cold or stress. It is classified as either monophasic, biphasic, or triphasic based upon the presence of – Pallor – Cyanosis – Rubor (hyperemia) • Primary Raynaud’s describes vasospasm not caused by an underlying disorder. It classically affects all fingers and is also known as Raynaud’s disease or idiopathic Raynaud’s. • Secondary Raynaud’s describes vasospasm associated with another disorder, such as an autoimmune disorder (e.g., scleroderma, systemic sclerosis). It generally has an asymmetric distribution and is also known as Raynaud’s syndrome and is usually more severe than primary Raynaud’s. EPIDEMIOLOGY Prevalence

• The exact prevalence is not known because of differences in diagnostic criteria. (0.5% to >20%) • Females > males • Primary > secondary

Morbidity

• Primary Raynaud’s rarely results in digital ulcers or gangrene. • Secondary Raynaud’s has variable morbidity that is related to the known cause.

ETIOLOGY/RISK FACTORS

• Primary Raynaud’s – Age <30 years – Exposure to vinyl chloride – Use of vibrating tools such as jackhammers – Use of certain medicines (vinblastine, cisplatin, beta-blockers, and migraine drugs) – Living in a cold climate – Smoking (controversial) – Thoracic outlet syndrome • Secondary Raynaud’s – Age >30 years – Immunologic diseases: Scleroderma, systemic sclerosis, CREST syndrome

– Pulmonary hypertension

PHYSIOLOGY/PATHOPHYSIOLOGY

• The pathophysiology is not fully understood and multiple theories/explanations exist. The most widely accepted mechanism includes vascular, neural components, and the coagulation system. There is excessive vasoconstriction relative to vasodilation and the neural component affects vascular tone and circulating mediators: – Vasoconstrictors: Increased levels of endothelin-1, neuropeptide Y, and platelet thromboxane A2; increased activity of α2C-adrenoreceptor expression can be increased in

some instances by estrogen (may play a role in primary Raynaud’s disease in women). – Vasodilators: Decreased levels of nitric oxide; and prostaglandins, which have vasodilating properties, could also be responsible for inhibition of platelet aggregation (coagulopathy) and increase in fibrinolytic activity. – Neural components: Calcitonin-gene-related peptide is a vasodilator released by nerve endings and is diminished in both primary and secondary RP. – Coagulation system activation may be secondary to vascular obstruction, platelet thromboxane A2.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Keep the patient normothermic, paying close attention to distal extremities. • Avoid hypotension and hypovolemia. • If an arterial line is needed, consider placing a femoral arterial line, if possible. • IV administration of vasoconstrictors should be avoided if possible. Alternatively, use smaller doses and with great caution, as well as consider inotropes and (warmed) fluid administration, as appropriate • Avoid the use of epinephrine and phenylephrine in regional blockade. • Continue perioperative medications such as calcium channel blockers

PREOPERATIVE ASSESSMENT SYMPTOMS

• Pain and stiffness in extremities when exposed to cold. Determine if the patient experiences pallor, cyanosis, or rubor. • Collect information that pertains to the underlying immunological cause.

History

• Identify primary versus secondary • Frequency of vasospastic episodes • Collect information related to underlying immunological cause

Signs/Physical Exam

Color change in digits to pale, cyanotic, or hyperemic. TREATMENT HISTORY

• Sympathectomy may be performed for severe disease. It is performed by removing the nerve attachments at the extremities and has variable success. • Nerve blocks to sympathetic nerves may be effective, but likely need to be repeated. • Amputation may be necessary if there is necrotic or gangrenous tissue (very rare).

MEDICATIONS

• First line treatment – Calcium channel blockers (nifedipine, amlodipine, and fenoldipine) provide vasodilation in the extremities, thus decreasing the frequency and severity of attacks, as well as possibly aid with the healing of skin ulcers. – Alpha receptor antagonists counteract the effects of endogenous norepinephrine (prazosin, doxazosin). • Second-line treatment – ACE inhibitors, angiotensin receptor blockers – Nitroglycerin paste can be applied topically for digital ulcers – Sildenafil – Fluoxetine – Prostaglandins DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

None in particular; order as needed for specific causes CONCOMITANT ORGAN DYSFUNCTION

There is some evidence that Raynaud’s patients are at increased risk for CVA.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Calcium channel blockers; consider having the patient take a regular or reduced dose of their home regimen with a small sip of water. • Administer anxiolytics as appropriate; anxiety has been known to exacerbate some types of Raynaud’s.

INTRAOPERATIVE CARE Choice of Anesthesia

• General and regional anesthesia are both acceptable techniques. • Regional blocks should not contain epinephrine or phenylephrine as they may cause an exaggerated vasoconstrictive response. • Use of tourniquets is controversial.

Monitors

• Standard ASA monitors • Use a noninvasive BP cuff (as opposed to a radial arterial line), if possible

Induction/Airway Management

• Be prepared to perform special airway management techniques in patients with small mouth openings (scleroderma) or limited neck mobility (rheumatoid arthritis). • Rapid sequence induction should be considered if the patient exhibits signs of esophageal dysmotility or gastric reflux.

Maintenance

• Ensure that the patient is euvolemic to avoid hypotension and maintain perfusion to digits. • Vasopressors should be used with caution due to the possibility of an exaggerated response. • Position patients with care to maintain optimal blood flow to the extremities (e.g., caution should be used with elevation of the hand in the lateral position). • Maintain normothermia – Warm the room to decrease radiation of heat from the patient into the cooler environment – Convection warming blankets reduce radiation of heat into the cooler environment as well as actively warm the patient. Consider implementing in the preoperative holding area – Warm IV fluids – In patients with advanced disease, use gloves and socks on their extremities. – Use reflective coverings – Hat covering

Extubation/Emergence

No special concerns unless systemic disease affects the respiratory system; otherwise use normal extubation criteria.

FOLLOW-UP BED ACUITY

Determined by underlying disease, surgical procedure, and intraoperative events MEDICATIONS/LAB STUDIES/CONSULTS

• Analgesia – Consider that pain may be from extremity vasoconstriction

COMPLICATIONS

Digital ischemia and/or gangrene

REFERENCES

1. Baumhäkel M, Böhm M. Recent achievements in the management of Raynaud’s phenomenon. Vasc Health Risk Manag. 2010;6:207–214. 2. Cooke JP, Marshall JM. Mechanism of Raynaud’s disease. Vasc Med. 2005;10:293–307. 3. Herrick AL. Pathogenesis of Raynaud’s phenomenon. Rheumatology. 2005;44:587–596.

4.

NIH. Raynaud’s Phenomenon http://www.niams.nih.gov/HealthInfo/RaynaudsPhenomenon/default.asp. Published April 2009. Accessed 9/19/2011. 5. Suter LG, Murabito JM, Felson DT, et al. The incidence and natural history of Raynaud’s phenomenon in the community. Arthritis. 2005;52(4):1259–1263. See Also (Topic, Algorithm, Electronic Media Element) • Hypothermia • Scleroderma • Pulmonary hypertension • Rheumatoid arthritis

CODES ICD9 443.0 Raynaud’s syndrome ICD10 I73.00 Raynaud’s syndrome without gangrene

CLINICAL PEARLS

• Keep the patient warm!!! • When an arterial line is indicated, assess the risks versus the benefits of placement in the radial artery; consider other proximal sites • Use IV vasoconstrictors with great caution • Avoid beta-blockers (especially nonselective) as they can cause unopposed alpha constriction.

RECOMBINANT ACTIVATED FACTOR VII (RFVIIA) Keyvan Karkouti, MD, FRCPC, MSc

BASICS DESCRIPTION

• Recombinant activated factor VII (rFVIIa; Novo Nordisk A/S, Bagsvaerd, Denmark) is similar to human plasma-derived activated factor VII. • It is supplied in single-use vials (as lyophilized powder) of 1, 2, 5, or 8 mg, and following reconstitution with normal saline, is administered intravenously over 2–3 minutes. • When administered in doses sufficient to achieve supraphysiological concentrations, it is a potent procoagulant that bypasses parts of the coagulation cascade. • Current indications are for treatment or prevention of bleeding episodes in patients with – Hemophilia A (factor VIII deficiency) with antibodies to factor VII – Hemophilia B (factor IX deficiency) with antibodies to factor IX – Acquired hemophilia (a rare condition that is associated with cancer, pregnancy, or autoimmune disorders, and is characterized by development of antibodies against factors VIII) – Congenital factor VII deficiency • The most common off-label use is for treatment of refractory bleeding in various settings, including cardiovascular surgery, trauma, and obstetrics. PHYSIOLOGY PRINCIPLES

• Normal coagulation – About 1% of circulating native factor VII is present in the activated form. – Following tissue injury, tissue factor (TF) is released from the subendothelium of injured vessels and forms a complex with circulating activated factor VII (TF–FVIIa). – The TF–FVIIa complex then initiates the coagulation cascade by activating factors X and IX on the injured cell surface. Activated factor X generates small amounts of thrombin, which activates platelets, factor VIII, and other cofactors. Activated factor IX diffuses to the surface of the activated platelets at the site of injury, and in combination with activated factor VIII, activates factor X. This leads to the thrombin burst that is needed for fibrin clot formation. • When administered in pharmacological doses (∼1,000 times greater than normal circulating levels), rFVIIa improves the coagulation process at the site of injury by – Directly (without forming a complex with TF) activating factor X on the activated platelets at the site of injury, and thus bypassing the need for factors VIII and IX. – Boosting the TF-dependent pathways • The amount of thrombin generated by rFVIIa is directly proportional to the administered dose. • The circulating half-life of rFVIIa, which is independent of dose, is about 3 hours in adults

and 1 hour in children.

DISEASE/PATHOPHYSIOLOGY

• Congenital or acquired hemophilia (approved indication). rFVIIa bypasses the need for factors VIII and IX to form fibrin clot. High doses (90 μg/kg every 2 hours) are required to achieve hemostasis. • Congenital factor VII deficiency (approved indication). Lower doses (15–30 μg/kg every 4–6 hours) are required to achieve hemostasis. • Functional platelet disorders (e.g., Glanzmann’s thrombasthenia, which is a congenital defect in the platelet GPIIb/IIIa receptor; an approved indication in Europe) require high doses similar to those used in patients with congenital hemophilia. • Thrombocytopenia. Conflicting effectiveness data; not approved in any jurisdiction for this indication. • Prophylactic use (to prevent anticipated bleeding). A recent meta-analysis of randomized studies in various settings, including cardiac surgery with cardiopulmonary bypass, hepatic resection, liver transplantation, traumatic pelvic fracture, spinal surgery, and radical prostatectomy, found modest benefits with rFVIIa in reducing blood loss and blood transfusion, with no statistical increase in thromboembolic events. The studies excluded patients at high risk for thromboembolic complications and the number of events was small. • Therapeutic use (to treat established bleeding). – Intracerebral hemorrhage: In a large phase III randomized study, rFVIIa at 80 μg/kg reduced hemorrhage expansion, but showed no benefit in clinical outcomes and doubled the incidence of arterial thrombotic events. – Trauma: In a large phase III randomized study in patients who received 4–8 units of packed red blood cells (pRBCs) and had ongoing blood loss, a total of 400 μg/kg of rFVIIa had a modest beneficial effect in blood loss and blood transfusion without increasing thromboembolic event rates. The trial was terminated early due to failure to show an improvement in mortality rates, which was the desired outcome. – Cardiac surgery with cardiopulmonary bypass: In a phase II randomized study in patients with postoperative bleeding in the ICU, 40–80 μg/kg of rFVIIa reduced re-exploration rates (by about 50%), transfusion rates, and blood loss. However, patients had a nearly twofold increase in thromboembolic events, although this difference did not reach statistical significance. • Rescue use (to treat bleeding that is refractory to maximal standard therapy): – No randomized trials have examined the use of rFVIIa as rescue therapy for refractory hemorrhage. – Observational studies in various settings (cardiac surgery, trauma, obstetrics), however, suggest that it can be effective and safe in treating refractory hemorrhage. – Risk may be prohibitive in patients at high risk for thromboembolic complications (e.g., previous stroke, carotid artery disease, and arterial insufficiency) or in patients with established disseminated intravascular coagulation or sepsis (due to systemic TF expression). – Dose recommendations vary, but 35–70 μg/kg repeated once or twice seems to be sufficient in most cases. – The risk–benefit profile is more favorable if rFVIIa is administered early in the course of

refractory hemorrhage rather than as a last resort. • A recent systematic review assessing the safety of the off-label use of rFVIIa found that it increases the risk of arterial thromboembolic adverse events by nearly twofold.

PERIOPERATIVE RELEVANCE

• When patients with approved indications present for invasive procedures or surgery, consultation with the hematologist is recommended to determine appropriate dosage and frequency of rFVIIa administration. • Off-label use considerations. Given its high cost and potential for thromboembolic complications (twofold increase in arterial thromboembolic adverse events), its prophylactic use should be avoided, particularly in patients with preexisting or acquired risk factors for thromboembolic complications. If considering its use as rescue therapy for refractory hemorrhage: – Assess appropriateness on a case-by-case basis, based on an individualized risk–benefit analysis that weighs the perceived risks of ongoing blood loss versus thromboembolic complications. – Use early in the course of hemorrhage, but correct the underlying coagulopathy and anemia as best as possible. For example, transfuse pRBCs to maintain a Hct >25%, platelets to maintain a count >80 × 109/L or to correct suspected platelet dysfunction (e.g., postcardiopulmonary bypass), transfuse fibrinogen or cryoprecipitate to reach a fibrinogen concentration of >1.5 g/L, transfuse plasma to reach an INR of <1.5. – Correct acidosis and hypothermia – Administer antifibrinolytic drugs if appropriate • Monitoring: There are no routine laboratory tests for monitoring the effects of rFVIIa, but the following tests may be relevant. – PT: A plasma-based assay that measures the time to clot formation by a TF source. It is shortened in all patients who receive rFVIIa irrespective of clinical response. However, if it is not normalized after rFVIIa therapy, it predicts a lack of response. – Activated PTT: A plasma-based assay that measures the time to clot formation by non-TF sources (celite or kaolin). It is shortened by rFVIIa, likely due to the ability of rFVIIa to directly activate factor X. It is not a reliable monitor of rFVIIa effect in patients who do not have hemophilia. – Thromboelastogram. A whole-blood assay that monitors the viscoelastic properties of the forming clot. rFVIIa shortens the time to clot formation and improves clot formation dynamics. It is not a reliable monitor of rFVIIa effect in patients who do not have hemophilia.

REFERENCES

1. Gill R, Herbertson M, Vuylsteke A, et al. Safety and efficacy of recombinant activated factor VII: A randomized placebo-controlled trial in the setting of bleeding after cardiac surgery. Circulation. 2009;120:21–27. 2. Grottke O, Henzler D, Rossaint R. Activated recombinant factor VII (rFVIIa). Best Pract Res Clin Anaestheiol. 2010;24(1):95–106.

3. Hauser C, Boffard K, Dutton R, et al. Results of the CONTROL trial: Efficacy and safety of recombinant activated factor VII in the management of refractory traumatic hemorrhage. J Trauma. 2010;69(3):489–500. 4. Hers I, Mumford A. Understanding the therapeutic action of recombinant factor VIIa in platelet disorders. Platelets. 2008;19(8):571–581. 5. Karkouti K, Beattie W, Arellano R, et al. Comprehensive Canadian review of the off-label use of recombinant activated factor VII in cardiac surgery. Circulation. 2008;118:331–338. 6. Levi M, Levy J, Andersen H, et al. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med. 2010;363(19):1791–1800.

7. Lin Y, Stanworth S, Birchall J, et al. Use of recombinant factor VIIa for the prevention and treatment of bleeding in patients without hemophilia: A systematic review and metaanalysis. CMAJ. 2001;183 (1):E9–E19. 8. Logan A, Goodnough L. Recombinant factor VIIa: An assessment of evidence regarding its efficacy and safety in the off-label setting. Hematology Am Soc Hematol Educ Program. 2010:153–159. 9. Mayer S, Brun N, Begtrup K, et al. Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358(20):2127–2137. 10. Roberts H, Monroe D, Hoffman M. Safety profile of recombinant factor VIIa. Semin Hematol. 2004;41(Suppl 1):101–108. 11. Roberts H, Monroe D, White G. The use of recombinant factor VIIa in the treatment of bleeding disorders. Blood. 2004;104(13):3858–3864. See Also (Topic, Algorithm, Electronic Media Element) • Fresh frozen plasma • Cardiopulmonary bypass (CPB) • Antifibrinolytics • Prothrombin time (PT) • Partial thromboplastin time (PTT)

CLINICAL PEARLS

• When patients with approved indications present for invasive procedures or surgery, consultation with hematology is recommended to determine appropriate dosage and frequency of rFVIIa administration. • If considering the use of rFVIIa for an unapproved/off-label condition such as refractory bleeding: – Obtain informed consent from the patient or next of kin, if at all possible – Assess appropriateness on a case-by-case basis, weighing the perceived risks of ongoing blood loss versus thromboembolic complications (assume a twofold increase in risk) – Use low doses (35–70 μg/kg, repeated once or twice if no response based on clinical assessment) – Use early in the course of hemorrhage, but correct the underlying coagulopathy as best as possible.

– Avoid concomitant use of other activated clotting factors (risks unknown and may be synergistic).

RECURRENT LARYNGEAL NERVE Jane C. Ahn, MD Sharon L. Lin, MD

BASICS DESCRIPTION

• The recurrent laryngeal nerve (RLN) provides both sensory and motor innervation to the larynx. – Supplies motor function to all intrinsic muscles of the larynx except for the cricothyroid muscle (innervated by the external branch of the superior laryngeal nerve). – Supplies sensory innervation to the vocal cords and subglottis. PHYSIOLOGY PRINCIPLES

• The RLN innervates all of the intrinsic laryngeal muscles except for the cricothyroid (innervated by the external branch of the superior laryngeal nerve). Specifically, all of the muscles that are innervated by the RLN (e.g., lateral cricoarytenoid, interarytenoid, vocalis, etc.), except for the posterior cricoarytenoid (only vocal cord abductor), adduct the vocal cords. • Coughing, gagging, and laryngospasm result from the efferent limb of the RLN

ANATOMY

• Originates as a branch of the vagus nerve (CN X). • The right and left vagus nerves exit the skull base via the jugular foramens. • In the neck, the right and left vagus nerves descend in the right and left carotid sheaths, respectively, between the internal jugular vein and internal carotid artery, and into the thoracic outlet. • Within the thorax, the vagus nerve gives off the recurrent laryngeal nerve. • The right RLN loops around the right subclavian artery at the level of the innominate artery and ascends along the tracheoesophageal groove behind the common carotid artery. • The left RLN follows the carotid artery into the mediastinum, loops around the aortic arch lateral to the ligamentum arteriosum. • Once the RLNs enter the larynx, they divide into motor and sensory branches. • The left RLN has a longer course (∼12 cm from aorta to cricothyroid) compared to the right RLN (∼5–6 cm from subclavian to cricothyroid), which may make it more prone to injury (1). • Blood supply to the RLN is provided by the inferior thyroid artery.

DISEASE/PATHOPHYSIOLOGY

• Injury to the RLN can occur from: • Inadvertent injury during surgical procedures • Tumor

• Aortic aneurysms (hoarseness may be one of the first presenting signs) • Trauma • Neurotoxic drugs • Viral or bacterial infections • Vascular insult • Surgical injury to the RLN can occur anywhere along the nerve’s course: Neck, chest, or skull base. • Most common surgical procedures citing RLN injury include • Thyroid and parathyroid surgery (33% of all surgical cases) (2) • Anterior cervical spine surgery (15%) (2) • Carotid endarterectomy (11%) (2) • Recurrent laryngeal nerve transmission may be transiently blocked when a supraclavicular, interscalene, or stellate ganglion block is performed. It typically manifests as hoarseness. • Recurrent laryngeal nerve paralysis • May be difficult to assess because many patients can be asymptomatic, especially if caused by slow growing tumor. • Unliateral palsy – Partial: Abductors are more vulnerable to injury. Therefore, partial nerve damage may result in a selective abductor paralysis with a VC that lies in the midline (adducted position) – Complete: Affects both adductors and abductors and results in a vocal cord that lies midway between adduction and abduction, just lateral to the midline. • Bilateral palsy – Partial: When the abductor is more severely affected than adductors, both vocal cords meet in the midline and cause complete airway obstruction – Complete: Vocal cords are positioned midway between abduction and adduction. Breathing is still possible with a glottic opening smaller than normal.

PERIOPERATIVE RELEVANCE

• Intraoperative nerve monitoring (spontaneous electromyelography [EMG]) has gained increasing popularity as a means of identifying the RLN during surgical procedures. The EMG detects and records muscle electrical activity continually. Mechanical irritation of the RLN triggers motor unit potential discharges and aids with detection of the nerve during surgical dissection as well as inadvertent manipulation and injury (retraction, cautery, scalpel). It requires the use of specialized equipment and precautions (3): • Use of a specialized endotracheal tube with electrodes at the level of the glottis. • Electrodes should make contact with the medial surface of the vocal cords (bilaterally) to allow monitoring. • An antisialagogue such as glycopyrrolate may help reduce saliva pooling at the vocal cords that can impede monitoring. • Frequent intraoperative suctioning may be required for saliva pooling. • Use short-acting muscle relaxants for intubation as long-acting neuromuscular blockers will prevent effective neuromonitoring. • The endotracheal tube may migrate after positioning for surgery with neck extension and should be considered if adequate EMG signal cannot be obtained.

• Regional anesthesia of the RLN and proper preparation can significantly aid successful awake fiberoptic intubation (4): • Thoroughly discuss procedure and reassure patient. • Administer adequate sedation for a calm, cooperative patient. • An antisialagogue such as glycopyrrolate can decrease secretions and improve visualization during fiberoptic guidance. • Topical local anesthetic can be applied through a variety of ways: Aerosol spray, atomizer, nebulizer, and gargling. • Translaryngeal nerve block delivers local anesthetic to areas supplied by the sensory component of the RLN (subglottis, upper trachea). • Identify structures by extending the patient’s neck and palpating the midline of the cricothyroid membrane. Insert a 20G or 22G needle with an attached 5 cc syringe (filled with 3–5 cc of local anesthetic) using the dominant hand and constantly aspirating. The nondominant hand is usually “anchored” to the patient and helps stabilize the needle. The presence of air bubbles in the syringe is an indicator of proper needle placement. Prior to injection, ask the patient to forcefully inhale, which will help spread local anesthetic. Potential complications of a translaryngeal block include bleeding, puncture of the membranous portion of the trachea, and systemic local anesthetic toxicity. Use with caution in patients where significant coughing is undesirable or those at high risk for aspiration as their cough reflex will be greatly impaired. GRAPHS/FIGURES

REFERENCE

1. Myssiorek D. Recurrent laryngeal nerve paralysis: Anatomy and etiology. Otolaryngol Clin N Am. 2004;37:25–44. 2. Rosenthal LHS, Benninger MS, Deeb RH. Vocal cord immobility: A longitudinal analysis of etiology over 20 years. Laryngoscope. 2007;117:1864–1870. 3. Randolph GW, Dralle H, Abdullah H, et al. Electrophysiologic recurrent laryngeal nerve monitoring during thyroid and parathyroid surgery: International standards guideline statement. Laryngoscope. 2011;121:S1–S16.

4. Simmons ST, Schleich AR. Airway regional anesthesia for awake fiberoptic intubation. Reg Anes Pain Med. 2002;27(2):180–192. See Also (Topic, Algorithm, Electronic Media Element) • Superior laryngeal nerve • Laryngospasm • Thyroidectomy • Anterior cervical disc fusion (ACDF) • Carotid endarterectomy • Local anesthetic systemic toxicity

CLINICAL PEARLS

• RLN injury can occur with head and neck surgical procedures, most commonly thyroid, anterior cervical spine, and carotid endarterectomy. Intraoperative nerve monitoring can decrease the incidence of RLN injury. • The RLN can be temporarily blocked with stellate ganglion blocks, interscalene blocks, or supraclavicular brachial plexus blocks. It manifests as hoarseness that is self-limiting and resolves when the local anesthetic wears off. • Regional anesthesia of the RLN can significantly facilitate awake fiberoptic intubation in difficult airway cases. The translaryngeal block should be performed with caution in patients at high risk for aspiration or in patients where severe coughing is undesired. • Unilateral RLN palsy may be asymptomatic or manifest as dysphagia and dysphonia. Partial bilateral RLN injury can manifest as airway obstruction and require emergent intubation.

RENAL BLOOD FLOW George J. Ranier, MD

BASICS DESCRIPTION

• Renal blood flow (RBF) refers to the volume of blood that perfuses the kidneys per unit time; renal plasma flow (RPF) refers to the volume of plasma that perfuses the kidneys per unit time. When discussing glomerular filtration rate (GFR), RPF is more appropriate (cellular components do not filter across glomerular capillaries). • The kidneys receive enormous blood flow relative to their mass; not only do they have a high metabolic requirement but they also function as a filtering and homeostatic organ. RBF is ∼20% of the cardiac output or 1 L/min in a 70 kg adult. PHYSIOLOGY PRINCIPLES

• Blood that enters the kidney eventually reaches the nephrons, the functional filtering units within the renal cortex. Each nephron consists of a system of small blood vessels (arterioles and capillaries) and a system of tubules. – Within the nephron, there are two sets of arterioles, afferent and efferent, that bring blood to and from the glomerulus, respectively. – The glomerulus is a capillary bed that is located within the renal cortex and is where the initial step of urine formation occurs via plasma filtration. Blood that is not filtered from the afferent arterioles, leaves the glomerulus via efferent arterioles and enters the peritubular capillary network. – The glomerulus is surrounded by the Bowman’s capsule, which collects the filtered plasma and channels it into a system of renal tubules that eventually dumps urine into the renal pelvis. • Blood flow in the kidneys, as in any other organ, can be described mathematically by Ohm’s law, where Pressure (P) = Flow (Q) multiplied by Resistance (R). Rearranging for flow, Q = P R. – RBF is dependent on mean arterial pressure (MAP) in the renal artery and vascular resistance of the renal arterioles, primarily the afferent and efferent arterioles. – Resistance to blood flow is determined by three factors: Vessel length, vessel radius, and blood viscosity. Resistance is inversely proportional to the 4th power of the vessel’s radius (Poiseuille’s law). • Blood flow through the renal cortex is unique, in that there are two sets of vessels. The first set is comprised of the afferent and efferent arterioles; the second set is comprised of capillaries that form the glomerular tuft and peritubular capillaries. – The resistance in these vessel sets makes up the majority of renal vascular resistance. – Because they are in series, a change in vascular tone will produce the same effect on RBF regardless of whether it is an afferent or efferent arteriole. – Changes in resistance are additive

– Because the peritubular capillaries are downstream from the afferent arterioles, glomerular capillaries, and efferent arterioles, they function as a lower pressure system. This is important, because for plasma filtration to occur at the glomerulus, a higher relative pressure is required, whereas, reabsorption within the peritubular capillaries requires a lower relative pressure. • A portion of the renal plasma flow (RPF) is filtered from the glomerular capillaries into the Bowman’s capsule. The volume of this filtrate produced over time is called the glomerular filtration rate (GFR). – The filtration fraction is the ratio of glomerular filtration to RPF; normal values are 0.2. – GFR for a healthy male adult is roughly 180 L/day. The high ratio of GFR to plasma volume allows the kidneys to excrete waste products and maintain tight control over the body’s internal milieu. – The filtration rate across the capillary is governed by the membrane’s surface area and permeability, as well as the filtration pressure. – For GFR, this allows derivation of the following formula: Kf(PGC – PBC – πGC), where Kf is the product of hydraulic permeability and surface area, PGC is the glomerular capillary hydrostatic pressure, PBC is the hydrostatic pressure in the Bowman’s capsule, and πGC is

the oncotic pressure of glomerular capillary plasma. GFR equals the product of hydraulic permeability and surface area (Kf) times the net filtration pressure (the mathematical sum

of hydrostatic and osmotic pressures acting across the glomerulus). • Autoregulation of the RBF and GFR blunts the otherwise deleterious effects of variable BP. Normal arterial BP can vary widely, and because the glomerular capillaries are thin-walled, they can be easily damaged by excessive BP. – Within a MAP of 80–180 mm Hg, RBF and GFR are relatively constant secondary to autoregulation. – Autoregulation occurs via two mechanisms: A myogenic response of vascular smooth muscle and tubuloglomerular feedback. The myogenic response is a fast response to stretch, while tubuloglomerular feedback acts via vasoconstrictive transmitters released by salt-sensing cells within the macula densa. – Within the nephron, alterations in afferent and efferent arteriolar tone regulate the hydrostatic pressure within the glomerular capillaries (PGC). This layer of control over the GFR is independent of overall RBF. – It is important to remember that while autoregulation blunts changes in RBF and GFR that would otherwise occur in direct response to changes in MAP, it does not totally negate those changes.

ANATOMY

• The kidneys are bilateral retroperitoneal organs, each weighing about 150 g and supplied by its own renal artery. • Functionally and anatomically, the kidney can be divided into an outer portion, or cortex, and an inner portion, or medulla. • Blood enters each kidney via its associated renal artery. The renal artery progressively divides into interlobar, arcuate, and then interlobular arteries. As these arteries branch, they

travel from the inner region of the kidney toward the cortex, where the interlobular arteries eventually give rise to the afferent arterioles. The afferent arterioles lead to glomeruli and form a “tuft” of capillaries. The glomerulus, with its surrounding Bowman’s capsule, forms the renal corpuscles (found only in the renal cortex). • Within the glomerulus, about 20% of the plasma is filtered into Bowman’s capsule, while the remaining 80% (plus cellular components) flows into the efferent arterioles. • Blood flowing from efferent arterioles may take several paths, depending on the location of the glomerulus within the kidney. Efferent arterioles that arise from cortical glomeruli subdivide into secondary capillaries, called peritubular capillaries, throughout the cortex. These eventually form veins by which blood exits the kidney. But the efferent arterioles that arise from juxtamedullary glomeruli take a different path. They course into the outer medulla, subdivide, and eventually form the vasa recta. Both vasa recta and the glomeruli contribute to the exchange of water and solutes that enable the kidney to regulate water and electrolyte balance. • All blood flowing into the kidney passes through the cortex, with a fraction of that blood flow then entering the medulla (the medulla receives less blood flow than the cortex). Because of this disparity of blood flow, in conditions of hypoperfusion the medulla is particularly vulnerable to ischemic damage. • The kidneys receive sympathetic innervation that controls RBF via afferent and efferent arterioles, juxtaglomerular apparatus, and portions of the tubules. Parasympathetic innervation has minimal influence.

DISEASE/PATHOPHYSIOLOGY

• There are two main causative factors of perioperative renal insults that can lead to acute kidney injury (AKI): Hypoperfusion/ischemia and nephrotoxic agents. AKI is diagnosed when there is an absolute increase in serum creatinine by 0.3 mg/dL or a 50% increase from baseline. Alternatively, it can be diagnosed as a reduction in urine output to <0.5 mg/kg/hr for ≥6 hours. • AKI can be grouped into three anatomic categories: Prerenal, intrarenal, and postrenal. • Prerenal AKI is the direct result of renal hypoperfusion, and is the most common cause of AKI. – Hypoperfusion may be caused by dehydration, acute blood loss, sepsis, congestive heart failure, aortic cross-clamping, renal artery thrombosis or embolism, or any other process that reduces extracellular fluid volume or circulating volume. – Complete lack of blood flow to the kidneys for 30–60 minutes can result in irreversible cell damage. – Drugs such as ACE inhibitors and NSAIDs can also cause prerenal AKI by a reduction in glomerular capillary perfusion. – In the early phase of prerenal AKI, the renal parenchyma is still intact and functional. During this period, autoregulatory mechanisms compensate to maintain the GFR by controlling the tone of afferent and efferent arterioles. – Prerenal AKI, if recognized, is often easily reversible but can progress to tubular cell injury and intrarenal AKI if unrecognized. – Prerenal AKI is also termed prerenal azotemia. • Intrarenal AKI, or intrinsic AKI, is classified by the portion of the nephron that is involved.

This can include the tubules, interstitium, vasculature, and glomerulus. – Acute tubular necrosis (ATN) involves specific injury to the renal tubules, and is most commonly the result of ischemia secondary to reduced RBF. It progresses through four distinct phases: Initiation, extension, maintenance, and recovery. Each phase is marked by characteristic cellular events and rates of glomerular filtration. In the first phase, or initiation phase, cellular ATP is depleted. Renal tubule epithelial cells are injured, swell, and form bullae. Next, during the extension phase, inflammation and microvascular congestion occur. As the insult progresses, cells become necrotic, detach, and form casts in the distal tubules. This obstruction further reduces GFR. During the third phase (or maintenance phase), GFR is at a nadir, but cells are undergoing repair. In the final recovery phase, GFR improves as cellular function slowly returns. In addition to renal hypoperfusion, there are numerous toxins that can cause ATN including IV contrast agents, aminoglycoside antibiotics, NSAIDs, the heme pigment released during rhabdomyolysis, and cocaine. – Diseases of the vasculature (micro or macro) can also cause intrinsic AKI via hypoperfusion. In the instance of microvascular disease, this occurs as the consequence of glomerular capillary thrombosis and microvascular occlusion. Examples include TTP, HELLP syndrome, and hemolytic–uremic syndrome. Macrovascular disease is characterized by atheroembolic events that occlude larger vessels. • Postrenal AKI, as the name implies, results from obstruction of urinary outflow. This obstruction can occur at any point from the tubules to the urethra. Examples include prostatic hypertrophy, genitourinary tumors, renal calculi, thromboses, uric acid precipitates from gout, and light chain proteins seen in patients with multiple myeloma.

PERIOPERATIVE RELEVANCE

• Anesthesia and surgery most often result in decreases in RBF, RPF, and GFR. Because the majority of anesthetic agents have negative effects on BP and cardiac output, this is not surprising. Additionally, the release of catecholamines that accompany surgical stimulation has the added impact of increasing renal vascular resistance, which reduces RBF and RPF, and may further decrease GFR. • Short periods of relative hypotension are not uncommon in the perioperative setting, due to either surgical or anesthetic manipulation. – With decreased RBF, the kidneys are often able to preserve filtration via compensatory mechanisms. Within the glomerular capillaries, filtration fraction is maintained by efferent arteriolar vasoconstriction. This decreases RBF but increases glomerular capillary pressure, and hence GFR. – Longer periods of hypotension, as may accompany cross-clamping, hemorrhage, or sepsis, result in afferent vasoconstriction and further decrease the RBF. The consequence is a reduction in filtration fraction and GFR, with deleterious effects on oxygen delivery and the potential for AKI. – The presence of oliguria, defined as urine output <0.5 mg/kg/hr, while concerning, is of limited predictive value for AKI, however. • Infusions of commonly used vasopressor drugs, such as norepinephrine, have been shown to decrease GFR in animals. This is likely true in humans; however, a survey of the literature

yields conflicting results. • The effects of neuraxial blockade are variable, depending on the degree to which BP and cardiac output drop. Because of the multitude of factors that influence RBF, including level of block, underlying disease, endogenous catecholamines, angiotensin, ADH, and many other circulating factors, it can be challenging to draw firm conclusions regarding the ultimate impact of regional anesthesia on RBF and GFR. However, several meta-analyses have found that epidural anesthesia reduces perioperative renal morbidity.

EQUATIONS

• Flow = MAP/Resistance; where Flow is renal blood flow, MAP is mean arterial pressure, and Resistance is renal arteriolar resistance (comprised mainly by afferent and efferent arterioles). – Glomerular Filtration Rate: GFR = Kf (PGC – PBC – πGC) • Filtration Fraction: FF = GFR/RPF

REFERENCES

1. Berne RM, Levy MN. Physiology. 2nd edn. St. Louis, MO: Mosby; 1988. 2. Eaton DC, Pooler JP. Vander’s Renal Physiology. 7th edn. New York, NY: McGraw Hill Medical; 2009. 3. Goldman L, Ausiello D. Cecil Textbook of Medicine. 23rd edn. Philadelphia, PA: Saunders; 2008. 4. Legrand M, Payen D. Understanding urine output in critically ill patients. Ann Intensive Care. 2011;1(1):13. 5. Mercatello A. Changes in renal function induced by anesthesia. Ann Fr Anesth Reanim. 1990;9(6):507–524. 6. Suleiman MY, Passannante AN, Onder RL, et al. Alterations of renal blood flow during epidural anesthesia in normal subjects. Anesth Analg. 1997;84(5):1076–1080. 7. Waugh WH. Modest pressure natriuresis and autoregulation during water diuresis in dogs. Blood Vessels. 1991;28(6):420–441. See Also (Topic, Algorithm, Electronic Media Element) • Glomerular filtration rate • Creatinine clearance • Epidural

CLINICAL PEARLS

• Even uneventful anesthetics and surgery often cause reductions in RBF and GFR. • The kidneys possess the ability via autoregulatory mechanisms to maintain GFR even when RBF is decreased and at times further reduce RBF by causing vasoconstriction.

RESCUE ECHOCARDIOGRAPHY Timothy R. Ball, MD William C. Culp, Jr., MD, FASE

BASICS DESCRIPTION

Unexplained perioperative hemodynamic instability is a class I indication for perioperative transesophageal echocardiography (TEE). Rescue echocardiography may be utilized to: • Quickly identify potential causes of unexplained hypotension • Assess the basic function of the left and right ventricles • Guide fluid management and inotropic medication administration during perioperative resuscitation PHYSIOLOGY PRINCIPLES

• A TEE uses high-frequency sound waves to depict the heart’s movement; esophageal placement brings the transducer within close proximity to the heart, and removes interference from the ribs or lungs. • Ejection fraction is calculated or visually estimated as the percent of volume ejected at end systole compared to the volume at end diastole. – End-systolic and end-diastolic volumes can be estimated by measuring left ventricular diameter or area. ANATOMY

• For a rapid and simple TEE examination, the midesophageal and trans-gastric views are the most helpful. – Midesophageal views allow rapid visualization of ventricular function, as well as mitral, aortic, and tricuspid valve functions. They include: The 4-chamber view The 5-chamber view The aortic valve short-axis view The aortic valve long-axis view – Trans-gastric view allows quick estimation of volume status and ventricular function as well as detecting pericardial effusions. This view of the left and right ventricles is attained by delicate probe anti-flexion from the midesophageal, 4-chamber view. PHYSIOLOGY/PATHOPHYSIOLOGY

• Contraindications for TEE – Absolute contraindications include a history of: Esophagectomy Esophagogastrectomy – Relative contraindications include a history of:

Esophageal trauma Esophageal stricture Esophageal fistula Esophageal surgery • Risks associated with TEE. The reported complication rates of TEE in the intraoperative adult population and in the adult ICU population are 0.2 and 2.6–4.0%, respectively. They include: – Oropharyngeal trauma – Esophageal perforation or other trauma – Unintended tracheal extubation or compression/obstruction of the trachea • Hypotension: While there are multiple etiologies for intraoperative hypotension, rescue TEE can quickly differentiate many of these causes. – Hypovolemia: Hemorrhage – Vasodilation: Anaphylaxis, sepsis – Systolic dysfunction: Ischemia, infarction • Cardiac tamponade: A large pericardial effusion with collapsed cardiac chambers. Symptoms can be non-specific with equivocal physical findings intraoperatively. TEE is the gold standard for diagnosis. • Pulmonary embolism: Can result from clot, air, fat, or other debris that enters the pulmonary vasculature. It results in a mechanical obstruction (dead space) with a secondary inflammatory response (shunting). • Shunt: Intracardiac shunts such as atrial septal defects and ventricular septal defects • Valvular pathology: Aortic stenosis, mitral stenosis, severe mitral regurgitation, and severe aortic insufficiency

PERIOPERATIVE RELEVANCE

• Midline insertion of the TEE probe in an endotracheally intubated patient may be performed with or without the aid of a laryngoscope. During insertion, the probe should be in a neutral position to avoid resistance. • Hypotension. Diagnosis may be made by imaging the left ventricle and measuring the ejection fraction, end-diastolic area, and end-systolic area. Diastolic area measurements function as reasonable, quick surrogates for true volume measurements in an emergency and are easily planimetered. – Hypovolemia: The appearance of normal left ventricular ejection fraction but low enddiastolic area – Vasodilation: Normal to high left ventricular ejection fraction with normal end-diastolic area and markedly low end-systolic area – Systolic dysfunction: Severely decreased ejection fraction of the left ventricle with very large end-diastolic and end-systolic areas. • Cardiac tamponade: Using midesophageal and trans-gastric views, a pericardial effusion may be evident around the whole of the heart or isolated. Tamponade physiology may be seen with collapse of the ventricles during diastole and atrial collapse during systole. • Pulmonary embolism: Using a midesophageal 4-chamber view may reveal a dilated right ventricle with a hypovolemic and even hyperdynamic appearing left ventricle; thrombus may be visualized in the main pulmonary arteries (uncommonly seen). Large venous gas

embolisms may look similar with gas bubbles visualized on TEE as bright white “fireflies” moving in the right ventricle. Extremely large gas embolisms may show the right ventricle filled with an echogenic bright white substance. If a large gas or air embolism is suspected, stop the surgical procedure including gas insufflation, and proceed as clinically indicated by ACLS protocol. Persistent hemodynamic instability necessitates insertion of a TEE probe and quick examination to rule out massive embolism or another potential cardiac cause such as myocardial ischemia. • Intracardiac shunts: May be seen in the midesophageal, 4-chamber view. Septal defects of the atria and ventricles will require superimposing Doppler color over the septa which may show flow across the septa. A bubble study with agitated saline may show a flow of bubbles across the interatrial septum if the right atrial pressures are higher than the left atrial pressures, but a lack of bubbles crossing the septum does not rule out a left to right shunt. • Aortic valve pathology: Using the midesophageal, aortic valve short-axis view (change the probe angle from 0 to 30% from a 4-chamber view) allows rapid visualization of the valve to estimate valve opening. A highly echogenic (bright white) valve that appears to not open well may be aortic stenosis. Superimposed color Doppler may show flow in the valve during diastole in cases of aortic valve insufficiency. • Mitral valve pathology: In the midesophageal, aortic valve long-axis view with superimposed color Doppler (change the probe angle from 0% to 120% in the 4-chamber view) the valve may have flow through it during systole indicative of regurgitation. A calcified valve that is highly echogenic and a very large left atrium (greater than 4 cm in diameter) may indicate mitral stenosis. The mitral valve may also be assessed in the standard midesophageal, 4-chamber view with superimposed color Doppler.

REFERENCES

1. Savage RM, Aronson S, Shernan SK. Comprehensive Textbook of Perioperative Transesophageal Echocardiography, 2nd ed. Lippincott Williams and Wilkins, 2011. 2. Practice Guidelines for Perioperative Transesophageal Echocardiography: An Updated Report by the American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists Task Force on Transesophageal Echocardiography. Anesthesiology. 2010;112(1):1–13. 3. Helberath JN, et al. Safety of Transesophageal Echocardiography. J Am Soc Echocardiogr. 2010;23(11):1115–1127. See Also (Topic, Algorithm, Electronic Media Element) • Cardiac tamponade • Pulmonary embolism • Venous air embolism

CLINICAL PEARLS

• During rescue TEE for a hemodynamically unstable patient, a quick limited examination is warranted to rule out hypovolemia, vasodilation, and left ventricular dysfunction. • In the presence of refractory hypoxemia, a rescue TEE may assist in the diagnosis of

pulmonary embolism or intracardiac shunt. • Valvular pathology may also be seen and may require expert echocardiographer’s assistance.

RESIDUAL LUNG VOLUME Gundappa Neelakanta, MD

BASICS DESCRIPTION

• Residual volume (RV) is the volume of air remaining in the lungs at the end of a maximal forced expiration. Although, by definition, it does not function in volume exchange, it continues to function in gas exchange. • At RV, the low lung volume and external compressive forces collapse terminal bronchioles, without causing atelectasis. The closure of these conducting zone bronchioles prevents alveolar collapse and the complete collapse of lung (large inspiratory efforts are needed to re-expand the alveoli). PHYSIOLOGY PRINCIPLES

• Residual volume – Normal values for RV are about 20% of the total lung capacity (TLC). In a normal sized adult male, the RV is about 1.2 L and in women about 1.0 L. – Gas exchange. The RV provides a constant supply of oxygen during inspiration and exhalation. Thus, it functions to provide stability and avoid rapid fluctuations in blood gas uptake. – Volume exchange. The RV cannot be expelled even with active, maximal exhalation. Terminal bronchioles close at low lung volumes and with external forces. This prevents complete alveolar and lung collapse that would require enormous inspiratory pressure to re-expand the lungs. • Volumes and capacities are a function of inward and outward forces. – The lungs are an elastic structure made of collagen and elastic fibers. The natural tendency of alveoli is to collapse inward due to the surface tension and contractile forces of the lung parenchyma. Expansion is, thus, resisted and requires either negative pressure across the lung and pleura (transpulmonary pressure) or positive pressure within the lung (mechanical ventilation) to offset the contractile forces. – The chest wall is also an elastic structure with properties similar to an expandable and compressible spring. The natural tendency is to expand outward. • Functional residual capacity (FRC). At the end of normal expiration, the outward expanding forces are exactly balanced by the inward recoil of the lungs, known as the FRC. This is an equilibrium point, and the volume at which the resting tidal volume begins and ends. It is comprised of the RV and expiratory reserve volume (ERV); FRC = RV + ERV. • Expiratory reserve volume (ERV). Defined as the volume from the end of normal exhalation (or FRC) to RV. This volume may be expelled when exhalation is active and exceeds the outward chest wall forces. • Measurement. Isolated measurements of RV are rarely performed in clinical practice. – Spirometry is a commonly used tool to measure inhaled and exhaled volumes. However,

because the RV does not participate in volume exchange, it cannot be measured in this manner. Thus, indirect methods need to be utilized. – Whole body plethysmograph is the “gold standard” in measuring lung volumes including RV. It can be used in children and does not require patient cooperation with breathing. However, it cannot be performed in a physician’s office and is available only in specialized pulmonary function laboratory. – Closed circuit breathing technique. The patient inhales a known concentration of an inert indicator gas (e.g., nitrogen, hydrogen, helium) from a spirometer. The gas spreads throughout the lungs and reaches an equilibrium. Exhaled gas is collected from the closed system and the RV is determined by the dilution and eventual equilibrium of the indicator gas. – Open circuit technique. The patient breathes 100% oxygen at maximal expiration (down to RV) and the concentration of nitrogen that is washed out in the expired gas is used to calculate the RV. – The closed and open circuit techniques may be limited by patient cooperation, the presence of trapped air in alveoli (due to closed airways), or alveoli that take much longer than the test period to equilibrate; these factors can result in inaccurate measurements. • Factors that affect lung and RV include age, gender, height, and weight. Therefore, lung volumes are usually expressed according to predicted volumes at a person’s body surface area and is expressed at standard body temperature (37°C), atmospheric pressure, and saturated with water vapor (BTPS). – Age: RV increases due to the loss of lung recoil and decreased resistance to the collapse of aged airways. – Position: There is a small but insignificant decrease in the RV due to a change in position from sitting to supine due to an increase in the amount of blood in the lung.

ANATOMY

• Alveoli are open and connect to the environment by conducting and transitional zones. – Conducting zone. Describes terminal bronchioles not in contact with pulmonary blood flow; does not take part in gas exchange. The closure of these bronchioles can occur without atelectasis. The closure of conducting zone bronchioles is, thus, important in the prevention of alveolar collapse and the complete collapse of lung. – Transitional zone. Describes small alveolated tubes that cannot be easily separated from the alveoli and take part in the gas exchange. They are susceptible to the surface tension changes and alveolar collapse can occur.

DISEASE/PATHOPHYSIOLOGY

• Increased RV and RV/TLC ratio (hyperinflation) results when emptying of the lungs is impaired. Damage to the alveolar septa, peripheral airways, and lung parenchyma can be seen with long-term smoking, alpha-1 antitrypsin, and emphysema. The decreased elastic recoil of alveoli and hence radial traction of small airways leads to closure of peripheral airways. With severe disease, bullae formation can occur (large air filled spaces that are not in contact with the pulmonary capillaries) resulting in wasted ventilation. – Oxygenation. This results in an increase in the alveolar to arterial oxygen gradient (A-a gradient).

– Ventilation. Elimination of carbon dioxide is not generally affected as CO2 is 20 times

more diffusible than oxygen. – FRC increases (FRC = RV + ERV) – Clinically, this manifests as an increase in the A–P diameter of the lungs, muffled heart sounds, and flattened diaphragm. • Decreased RV results when external forces prevent adequate expansion; restrictive lung disease. Oxygenation may be normal especially at rest. In advanced disease, hypoxia is present due to V/Q mismatch and diffusion defect. CO2 elimination is not affected. FRC decreases (FRC = RV + ERV) – Parenchymal disease (interstitial pulmonary fibrosis). RV is decreased, FEV1 is preserved, and the ratio of FEV1 to the FEV is often increased.

– Chest wall deformity includes scoliosis and pectus excavatum. Lung volumes are only modestly decreased in these patients. – Neuromuscular disorders include Duchenne’s muscular dystrophy, myasthenia gravis, and amyotrophic lateral sclerosis. Respiratory muscle weakness results in low lung volumes.

PERIOPERATIVE RELEVANCE

• Anesthesia and medications. – Increased RV and RV/TLC states are at risk of pneumothorax during IPPV and with the administration of nitrous oxide. Inhalation induction may be delayed due to the increased lung volumes (lower rate of rise in the alveolar concentration/fraction for a given inspiratory fraction, hence decreased FA/Fi) or dead space (pulmonary blood does not perfuse the alveoli and cannot deliver agent to the brain). – Decreased RV states have a decreased FRC that predisposes to rapid hypoxemia as well as faster uptake of inhaled anesthetic agents (brain tissue concentrations are achieved more rapidly due to a faster rate of rise in the FA/Fi ratio). • Abdominal surgery. Increases RV, but decreases ERV to a greater extent, with consequent decreases in the FRC. Lower abdominal procedures can decrease the ERV by 25%, while upper procedures can result in a 60% decrease. • Lung resection. Preoperative clearance often involves an assessment of the RV and TLC to determine suitability for surgery and predict postoperative pulmonary function. An RV/TLC ratio >50% predicts high risk for pulmonary resection. A RV/TLC ratio >40% may be associated with a 30% mortality versus 7% when the RV/TLC ratio is <40%. • Severe COPD may be treated with lung volume reduction surgery (LVRS). The loss of outward circumferential pull leads to collapse of the small airways. Reducing the overall lung volume by multiple, peripheral wedge resections can restore the elastic pull on the small airways and decrease obstruction; this can facilitate emptying of alveoli with resultant decreases in the RV. Patients with severe, upper-lobe predominant emphysema, profound breathlessness, identifiable distension, and hyperinflated lung tissue (FEV1 <40%, RV >150%, TLC >120% of predicted values) are good candidates for LVRS.

EQUATIONS

TLC = VC + RV; where TLC is the total lung capacity, VC is the vital capacity, and RV is

residual volume

GRAPHS/FIGURES

ADDITIONAL READING

• Hedenstierna G. Alveolar collapse and closure of airways: Regular effects of anesthesia. Clin Physiol Func Imaging. 2003;23(3):123–129. • Levitzky MG. Alveolar Ventilation (Chapter 3). Levitzky MG: Pulmonary Physiology, 7e: http://www.accessmedicine.com/content.aspx?aID =2773620. • Naunheim KS, et al. Long-term follow-up of patients receiving lung-volume-reduction surgery versus medical therapy for severe emphysema by the National Emphysema Treatment Trial Research Group. Ann Thorac Surg. 2006;82(2):431–443. • Rehder K, Marsh HM, Rodarte JR, et al. Airway closure. Anesthesiology. 1977;47(1):40–52. • Stocks J, Quanjer PH. Reference values for residual volume, functional residual capacity and total lung capacity. ATS Workshop on Lung Volume Measurements. Official Statement of the European Respiratory Society. Eur Respir J. 1995;8(3):492–506. • Wahba RM. Airway closure and intraoperative hypoxaemia: Twenty-five years later. Can J Anaesth. 1996;43(11):1144–1149.

See Also (Topic, Algorithm, Electronic Media Element) • Asthma • Functional residual capacity • Smoking

CLINICAL PEARLS

• Isolated measurement and interpretation of RV is uncommon. • Increased RV may be seen with emphysema and alpha-1 antitrypsin deficiency. There is a loss of circumferential outward pull of the small airways leading to small airway collapse and trapping of air in the alveoli. • Decreased RV may be seen with restrictive lung disease (parenchymal disease, chest wall deformity, neuromuscular disorders).

RESPIRATORY ALKALOSIS Mariya Svilik, MD

BASICS DESCRIPTION

• Respiratory alkalosis is a physiologic state of high pH (>7.45) and low partial pressure of carbon dioxide (paCO2) (<35 mm Hg). • This clinical condition is caused by hyperventilation that results in excessive elimination of CO2. • Respiratory alkalosis is commonly classified as either: – Acute respiratory alkalosis: Low paCO2, high pH, onset of 6–24 hours.

– Chronic respiratory alkalosis: Low PaCO2, near normal pH, onset of >6–24 hours. The

longer duration allows the body time to compensate by excreting sodium bicarbonate ions renally. • Since pH homeostasis is essential for proper protein function, and consequently organ function, its derangement affects multiple organ systems including the cerebral, cardiovascular, renal, pulmonary, and GI systems.

EPIDEMIOLOGY Prevalence

In the general, in-patient population, the incidence can be as high as 26% (1).

Prevalence

Varies greatly with disease etiology ETIOLOGY/RISK FACTORS

• Central nervous system (CNS). The medullary respiratory center is affected by disease processes and input from peripheral and central receptors, as well as voluntary control from the cerebral cortex: – Infection – Tumor – Brain injury – Drug poisoning such as salicylates – Caffeine – Liver failure – Fever – Pain – Anxiety • Pulmonary – Hypoxia governs breathing to a greater extent than CO2, thereby triggering the respiratory

center to increase the respiratory rate and tidal volume (minute ventilation). It can result from pulmonary emboli, pneumonia, pneumothorax, pulmonary edema, aspiration, interstitial lung disease, asthma, emphysema or chronic bronchitis. Additionally, ascent to high altitudes can decrease the fraction of inspired oxygen. – Iatrogenic: Mechanical hyperventilation • Cardiovascular: Congestive heart failure, right-to-left shunt, and anemia result in lowoxygen states that stimulate peripheral receptors. • Catecholamines increase ventilation via direct dilation of the smooth muscles of the bronchi. • Nicotine and acetylcholine stimulate the carotid and aortic bodies. • Hyperthyroidism increases the respiratory drive in response to hypoxemia and hypercapnia. The specific mechanism is not known. • Systemic sepsis results in tissue hypoxia as well as metabolic acidosis. In addition, the lungs provide a large surface area for heat exchange thus helping to control body temperature via neural input from the hypothalamus. • Pregnancy: Respiratory alkalosis is a normal physiologic response. A sustained elevation of progesterone causes a hypoxic ventilatory response as a result of its effect on carotid bodies, while estrogen acts on the CNS thereby augmenting carotid sinus nerve activity on ventilation.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Carbon dioxide is a product of cellular metabolism and is excreted via the lungs. It is transported in blood in three main ways: – Bicarbonate ions in red blood cells (RBCs) and plasma (majority). After entering the RBC, CO2 combines with water via carbonic anhydrase to form carbonic acid; it is then broken down to H+ and HCO3−. The H+ binds to deoxyhemoglobin, while HCO3− is extruded

from the cell in exchange for a Cl- ion to maintain electroneutrality. This reaction also occurs in the plasma, but at a slower rate due to the lack of carbonic anhydrase. This mechanism for transport also serves to buffer the extracellular fluid compartment against pH derangements. – Bound to hemoglobin (Hgb) (carbaminohemoglobin) and protein – Dissolved in blood; a small percentage exists in the gas form and exerts partial pressure that can be measured on an arterial blood gas reading. • Chemoreceptors exist in the central and peripheral system and serve to detect changes in CO2 and pH; they send input to the medullary respiratory center. – Central chemoreceptors are the primary regulators of respiratory rate and are located on the ventrolateral surface of the medulla oblongata in the brain; they detect changes in pH of CSF. Since CSF is separated from the blood, electrolytes do not diffuse freely into CSF. However, volatile gases such as carbon dioxide can move easily through the barrier. Once CO2 is in the CSF, it can react with water to eventually produce hydrogen ions and

bicarbonate and thereby alter the CSF pH. With time, the chemoreceptor will eventually desensitize to the derangement. – Peripheral chemoreceptors: aortic body and carotid body. Unlike the central chemoreceptors, they do not desensitize to stimulus. The aortic body receptors detect

changes in the paO2 and paCO2 of the blood, whereas the carotid body receptors detect

changes in the paO2, paCO2, and pH of the blood. The chemoreceptors serve to increase or

decrease the respiratory rate and tidal volume, hence adjusting ventilation. Output from the peripheral receptors reaches the central respiratory centers, which in turn affect the ventilation. • High altitude and hypoxia govern breathing to a greater extent than CO2. When the paO2 falls below 100 mm Hg, neural activity from peripheral receptors begins to increase. However, the paO2 needs to reach 60–65 mm Hg for a substantial increase in minute

ventilation to occur and make the individual dependent on hypoxic ventilatory drive. This, consequently can result in respiratory alkalosis. • pH derangements result when the buffering mechanisms are overwhelmed. – Henderson Hasselback equation: – HCO3− + H+ ←→ H2CO3 ←→ CO2 + H2O – Acute: pH = 0.008 × (40–paCO2) and the ΔHCO3− = 0.2 × ΔpaCO2

– Chronic: pH = 0.017 × (40–paCO2) and the ΔHCO3− = 0.5 × ΔpaCO2

• Electrolyte derangements – Hypokalemia. To offset the pH imbalance, hydrogen ions shift from intracellular to the extracellular space via the Na+-H+ ion exchanger (Na+ moves into the cell). The increase in intracellular Na+ stimulates the Na+-K+-ATPase, which results in a secondary intracellular shift of K+. – Hypocalcemia. Alkalosis results in an increased negative charge on albumin that leads to increased Ca++ binding and decreased unbound Ca++ ions. Additionally, calcium binds to bone in exchange for hydrogen ions stored in bone material. Hypocalcemia can result in tetany and paresthesias. • Decreased cerebral blood flow (CBF). CBF is directly proportional to paCO2 values between 20 and 80 mm Hg. Normal brain blood flow is 50 mL/100 g/min. A paCO2 value of 20 mm

Hg will result in severely decreased CBF to 25 mL/100 g/min. Acute decreases below this value can produce EEG signs of cerebral ischemia. • Cardiovascular system. Hypocalcemia can result in dysrhythmias and vasodilation. • Pulmonary system. Hypocarbia can result in decreased pulmonary vascular resistance as well as increased bronchial smooth muscle tone from hypocalcemia. • Medications. Respiratory alkalosis can potentiate the effects of nondepolarizing neuromuscular blockade secondary to hypokalemia and alkalemia.

PREVENTATIVE MEASURES

• Perioperatively, the end-tidal CO2 should be monitored with adjustments made to the

respiratory rate and tidal volume as appropriate. Arterial blood gas (ABG) measurements can confirm paCO2 and pH values, particularly when there is an increase in dead space

ventilation. • Increases in minute ventilation, particularly when spontaneously ventilating, may suggest pain or awareness under anesthesia and administration of opioids or deepening of the

anesthetic should be considered.

PREOPERATIVE ASSESSMENT • Respiratory alkalosis is a relatively common abnormality seen in in-patients. It may not always be recognized preoperatively; however, a history of recent infection, liver or thyroid disease, as well as psychological disturbances, may be clues to its presence. • Diagnostic tests and interpretation – ABG: Identify an elevated pH with a low paCO2. The pH value can aid with distinguishing between acute and chronic states. – Chemistry panel: To determine the effect on electrolytes such as K+, Cl−, HCO3−, and

Ca++. The bicarbonate value, which is decreased by the kidneys, can aid with distinguishing between acute and chronic states. – Liver function tests: To determine if liver failure may be the cause of respiratory alkalosis. – Chest x-ray: Can help confirm pneumonia, pulmonary congestions, pneumothorax, lung disease, pulmonary edema, cardiac enlargement, and congestion. – Chest CT: If pulmonary embolism is suspected – Head CT/MRI: Help to confirm an injury, tumor, or CVA – CBC: If sepsis is suspected – Cultures: If sepsis is suspected; if a CSF infection is suspected, perform cultures on CSF fluid.

DIFFERENTIAL DIAGNOSIS

Respiratory alkalosis is a unique disorder that is always a sign of some other underlying disease; thus, the etiology is, in itself, the differential diagnosis.

TREATMENT • When detected preoperatively, the underlying cause should be sought and corrected. If found intraoperatively, it is most commonly the result of mechanical hyperventilation; however, other causes should also be at least considered. • Medication: If alkalosis is >7.60, careful titration of HCl, ammonium chloride, and arginine hydrochloride can be administered. All three medications must be administered carefully under constant supervision. Although they have other uses, their main function here is as systemic acidifiers. The HCl component of each of the drugs serves to buffer excess bicarbonate. • Additional treatment: If alkalemia is severe, consider patient intubation and mechanical (hypo)ventilation as well as hemodialysis. In cases of chronic respiratory alkalosis, correction to normocarbia needs to be gradual to avoid metabolic acidosis; the body compensates via the kidneys by excreting extra HCO3− to normalize the pH. • Complementary and alternative therapies: In cases of anxiety or panic attacks, the patient can be instructed to breathe into a paper bag, thereby causing some of the CO2 to be rebreathed. Patients can be taught to identify an episode of an acute anxiety attack and

practice this maneuver until the panic attack and resultant hyperventilation subsides. They can also carry out relaxation and biofeedback exercises in order to manage the severity of their anxiety and panic attacks. • Surgical treatment of hyperthyroidism and liver disease can return the paCO2 to normal.

REFERENCES

1. alange P, Carlone S, Galassetti P, et al. Incidence of acid-base and electrolyte disturbances in a general hospital: A study of 110 consecutive admissions. Recenti Prog Med. 1990;81(12):788–791. 2. Terzano C, Di Stefano F, Conti V. Mixed acid-base disorders, hydroelectrolyte imbalance and lactate production in hypercapnic respiratory failure: the role of noninvasive ventilation. PLoS One. 2012;7(4):e35245. 3. h YK. Acid-base disorders in ICU patients. Electrolyte Blood Press. 2010;8(2):66–71. 4. uintanilla AP. Acute acid-base disorders. 2. Specific disturbances. Postgrad Med. 1976;60(5):75–83 See Also (Topic, Algorithm, Electronic Media Element) • Metabolic alkalosis • Hypokalemia • Hypocalcemia • Minute ventilation • Respiratory acidosis • Cerebral blood flow

CODES ICD9 276.3 Alkalosis ICD10 E87.3 Alkalosis

CLINICAL PEARLS

Perioperatively, the anesthesia provider must keep in mind that respiratory alkalosis can result in • Cerebral ischemia. Rapid correction may alternatively result in vasodilation and intracranial hypertension. Often during surgery, patients are intubated and are placed on mechanical ventilation. Adjustments made to the ventilator tidal volume and respiratory rate can lead to rapid correction of paCO2 to normal. However, such rapid corrections could result in acute changes in CSF pH and consequently cerebral blood flow. • Cardiac instability from hypotension or dysrhythmias.

• An increase in the affinity of O2 to Hgb will shift the O2–Hgb dissociation curve to the left.

This makes it more difficult for Hgb to offload oxygen to tissues and can potentially cause tissue hypoxia. • Prolonged respiratory depression from opioids (alkalemia). • A potentiated effect of nondepolarizing neuromuscular blockade (hypokalemia and alkalemia).

RESPIRATORY SYSTEM COMPLIANCE Craig R. Cook, MD, PhD Andrea Vanucci, MD, DEAA

BASICS DESCRIPTION

• Respiratory compliance is defined as the change in respiratory system volume divided by the change in distending airway pressure; C = ΔV/ΔP. • Respiratory system (RS) compliance is the composite of chest wall (CW) compliance, and lung (L) compliance. RS, CW, and L compliances are concepts of respiratory mechanics, the branch of physiology studying the forces causing or opposing air movement in and out of the lungs. • Compliance is an index of the elastic properties of the respiratory system; it is also a determinant of alveolar gas flow and work of breathing. • The inverse, or reciprocal, of compliance is elastance: E = ΔP/ΔV. • Measuring lung compliance provides useful data to quantify the severity of lung pathology and to decide ventilatory strategies in the operating room and intensive care unit (ICU) (1) [A].

PHYSIOLOGY PRINCIPLES

• Respiratory system compliance is the change in milliliters per cmH2O pressure (mL/cmH2O).

It provides an objective measure and means to discuss an elastic structure’s ability (or inability) to “stretch.” • Compliance values vary with lung volume, and, thus, are not linear. CW, L, and RS compliance are maximal at the functional residual capacity (FRC). – FRC is defined as the balance point between the natural tendency of the CW toward expansion and of the lung toward collapse. Such balance determines the lung volume at rest. – When lung values are above or below the FRC, compliance values decrease; there is a reduced change in volume for a given pressure. • Compliance is analogous to electrical capacitance, where chest wall and lung compliance are in series. It is also calculated in the same manner: 1/total compliance = 1/lung compliance + 1/chest wall compliance. Typical values: – Total compliance: ∼100 mL/cmH2O – C(L): ∼150–200 mL/cmH2O – C(CW): ∼200 mL/cmH2O

• Elastance is the reciprocal of compliance and is a measure of the RS’s tendency to recoil toward its original dimensions following deformation and upon removal of a distending or compressing force; it is analogous to the behavior of a stretched rubber band or spring. – Chest wall recoil is due to anatomical structures such as the ribs and chest wall muscles,

whereas, lung recoil is due to elastin fibers and the surface tension forces in alveoli. – Inspiration is caused by the active contraction of the diaphragm and other inspiratory muscles. At rest, expiration is mainly passive and is due to relaxation of respiratory muscles and the elastic recoil of lungs. – Elastin protein is found in the lungs, as well as arteries, skin, and bladder. Following inhalation, or stretch, it provides the force to return the lungs to their FRC. Pathologic disease states include Marfan syndrome or α-1 antitrypsin disease. • The surface tension of alveoli favors collapse of the lung following LaPlace’s law: P = 2T/R, where P is pressure within the alveoli measured in pascals (Pa), T is the surface tension of the alveoli measured in Newtons/meter, and R is the radius of the alveoli measured in meters (m). Surfactant is a lipoprotein complex produced by type 2 alveolar cells. It decreases alveolar surface tension (T), and hence increases compliance, decreases work of breathing, and helps to prevent alveolar collapse.

ANATOMY

Determinants of respiratory system compliance include the lungs and chest wall (and any associated disease or pathology). Of note, the abdominal contents are a major determinant of respiratory compliance; increased intra-abdominal pressure (obesity, pneumoperitoneum, pregancy) translates to decreased compliance. DISEASE/PATHOPHYSIOLOGY

• In a normal respiratory system, tidal volume ventilation should occur along the rectilinear portion of the compliance curve. In disease states, however, it becomes more difficult to adequately deliver tidal volume ventilation within the limits of the rectilinear portion of the compliance curve. • Restrictive pulmonary disorders decrease compliance of the lungs, chest wall, or both. – Lung compliance: Pulmonary edema, fibrosis, pneumonia, acute respiratory distress syndrome (ARDS), acute lung injury (ALI), pleural effusions, pneumothorax, mediastinal masses, and vascular engorgement – Chest wall: Kyphoscoliosis and muscular disease – Both: Increased abdominal pressure from pregnancy, ascites, obesity, and laparoscopic procedures. • Obstructive lung disease. In emphysema or bullous lung disease, although static compliance can be increased, dynamic compliance may be decreased. • Age affects chest wall compliance. In the elderly, the thorax is stiff due to ossification and increases outward forces. In infants, the CW has a very high compliance; as a result, during passive expiration, the outward chest wall recoil does not oppose the lungs tendency toward collapse. This may cause the FRC to decrease below the airway’s closing pressure. Positive end-expiratory pressure (PEEP) may counteract this phenomenon and preserve FRC, and hence, oxygenation and ventilation.

PERIOPERATIVE RELEVANCE

• In the operating room, the anesthesia provider can assess dynamic and static compliance. – The anesthesia machine is capable of measuring pressures during “peak” and “plateau,” or dynamic and static inspiratory breaths, respectively.

– These values and curves allow inferences and calculations of the compliance. – Some machines are capable of generating pressure–volume curves; where the slope is equal to compliance at a specific volume. • Dynamic compliance (Cdyn) is specific to the peak inspiratory or distending compliance of the lung and chest wall. – C(dyn) = V(t)/(Ppeak – PEEP); volume change divided by peak airway pressure minus end-expiratory pressure. – Decreased dynamic compliance is seen with atelectasis, asthma, pulmonary edema, pleural effusions, ascites, abdominal retractors or packing, pneumoperitoneum, and endobronchial intubation. – Artifactual increases in dynamic pressure measurements result from the breathing tube and circuit apparatus: ETT diameter, secretions, kinking; ventilator settings. They do not actually change compliance. • Static compliance (Cstat) is specific to end- inspiration, when no gas flow is present. It is mainly determined by the lung and chest wall compliance, but not by ventilator settings, the breathing circuit, or ETT. – C(stat) = V(t)/(Pplat – PEEP); volume change divided by plateau pressure minus endexpiratory pressure – Intrinsic PEEP (assessed by means of an end-expiratory pause) must be considered, otherwise compliance could be miscalculated. • Specific compliance: C/FRC. It mirrors the elasticity of the aerated lung tissues. • Pressure–volume curves can be constructed to reflect changes in static and dynamic compliance. Volume (y-axis) is plotted as a function of pressure (x-axis) and the slope corresponds to compliance. Both inspiratory and expiratory compliance curves can be constructed. – The curves are nonlinear, but sigma shaped, when compliance is tested over a sufficient range of vital capacity. In most patients, a lower and a superior inflection point can be detected. These points correspond to volumes of the respiratory system at which its elastic properties change rapidly. If present, the lower inflection point (LIP) identifies an abrupt increase in the compliance that has been traditionally interpreted as a sign of lung tissue recruitment. Alternatively, the upper inflection point (UIP) signifies an abrupt decrease in compliance as a result of overdistention of alveoli. Hysteresis between the inspiratory and expiratory compliance curves is also observed. Hysteresis reflects that, upon expiration, at a given pressure, the lungs exhibit greater volume compared to inspiration. Thus, the expiratory and inspiratory limbs of the compliance curve do not overlap. • Compliance curves are utilized in the ICU to assess severity of lung diseases, guide ventilatory management, and evaluate progression of the lung disease or efficacy of undertaken treatments. • General anesthesia affects chest wall compliance. Volatile IV anesthetics as well as paralysis result in diaphragm relaxation with consequent cranial displacement of the abdominal contents. This results in increased intra-abdominal pressure with decreased CW and L compliance (2)]A]. • Intraoperative clinical changes in compliance can be anticipated based on patient-related and procedure-related risk factors. Ventilator settings (PEEP, TV, RR) should be adjusted

accordingly. Decreased compliance can be seen with: – Patient-related risk factors: Age, high BMI, smoking, respiratory infections, pregnancy, abdominal distension, chest deformations. – Procedure-related risk factors: Thoracic and abdominal procedures, Trendelenburg, surgical retractors, cardiopulmonary bypass, one lung ventilation, and pneumoperitoneum. – Atelectasis from pulmonary edema, low tidal volumes, pulmonary disease, foreign body aspiration, and endobronchial intubation can decrease compliance. – An abrupt increase in peak pressures, in the absence of any of the previously mentioned changes, may suggest a tube kinking or occlusion by secretions, as well as an asthma attack. – Increases in compliance may also be seen with alveolar recruitment, resolution of lung parenchyma pathological processes, and changes in ventilator setting or in CW compliance. • ARDS and ALI are disorders that profoundly affect pulmonary compliance. – During lung expansion with positive pressure inhalation, new alveoli are recruited and start to open (reflected by the LIP on pressure-volume curves). – On exhalation, some alveoli collapse or are derecruited (reflected by a steep slope change in the expiratory pressure-volume curve). – The exact physiologic meaning of the LIP is still debated. Traditionally, its presence has been interpreted as the airway pressure value at which many alveolar units are recruited simultaneously, but studies in ICU patients have shown that it may be more influenced by the CW than the L component. Additionally, CT studies have shown that recruitment occurs along the entire compliance curve, independent of the LIP. – Maintaining airway pressures between the LIP and UIP may prevent cyclic alveolar derecruitment and overdistention. Ventilation outside the inflection points can cause shear stress with resultant release of inflammatory mediators that can have both a local and systemic effect and contribute to multiorgan failure. Traditionally, in ICU patients, the PEEP level is set above the LIP (2,3,4)[A]. • Respiratory compliance is also a determinant of the respiratory work of breathing, and influences the patient’s ability to sustain unsupported ventilation. Monitoring compliance can provide additional useful information in a ventilator weaning process. • 1/total compliance = 1/lung compliance + 1/chest wall compliance • Total elastance = lung elastance + chest wall elastance • C(dyn) = V(t)/(Ppeak – PEEP) • C(stat) = V(t)/(Pplat – PEEP) • LaPlace’s law: P = 2T/R; P is pressure within the alveoli measured in pascals (Pa), T is surface tension of the alveoli measured in newtons/meter, R is radius of the alveoli measured in meters (m).

GRAPHS/FIGURES

FIGURE 1. Pressure-volume curve reflecting volume as function of pressure; the slope corresponds to compliance. The upper inflection point (UIP) represents an abrupt decrease in compliance from overdistention of alveoli. The lower

inflection point (LIP) reflects an abrupt increase in compliance from lung tissue recruitment. Hysteresis is also demonstrated.

REFERENCES

1. Perchiazzi G, Giuliani R, Ruggiero L, et al. Estimating respiratory system compliance during mechanical ventilation using artificial neural networks. Anesth Analg. 2003;97:1143–1148. 2. Pelosi P, Luecke T, Rocco PR. Chest wall mechanics and abdominal pressure during general anaesthesia in normal and obese individuals and in acute lung injury. Curr Opin Crit Care. 2011;17(1):72–79. (A) 3. arris RS. Pressure-volume curves of the respiratory system. Respir Care. 2005;50(1):78–98. (A) 4. lbaiceta GM, Blanch L, Lucangelo U. Static pressure-volume curves of the respiratory system: Were they just a passing fad? Curr Opin Crit Care. 2008;14(1):80–86. (A)

ADDITIONAL READING

• Stahl CA, Moller K, Schumann S, et al. Dynamic versus static respiratory mechanics in acute lung injury and acute respiratory distress syndrome. Crit Care Med. 2006;34(8):2090–2098.

See Also (Topic, Algorithm, Electronic Media Element) • Functional residual capacity • Acute respiratory distress system • Atelectasis

CLINICAL PEARLS

• Compliance can be assessed and monitored intraoperatively and in the ICU. Pressure– volume loops are graphically displayed by several anesthesia machines and ICU ventilators. These graphs inform us of dynamic compliance values and changes, as well as about modifications of inspiratory and expiratory resistances. If compliance decreases, the P–V loop moves down toward the pressure axis. Over distention can be detected by a pronounced increase in airway pressure at end-inspiration with a very modest change in volume. Increased respiratory resistances determine an enlargement of the area of hysteresis.

• Rapid changes in compliance in intraoperative patients must be investigated to rule out possible complications, like asthma, and obstruction or kinking of the ETT. • If the change in compliance is caused by pneumoperitoneum insufflation, alarms based on airway pressures should be reset accordingly to the new baseline.

RETAINED PLACENTA REMOVAL Swarup S. Varaday, MBBS, FRCA, FCARSI

BASICS DESCRIPTION General

• The third stage of labor denotes the interval between vaginal delivery of the neonate and placental separation. Normally, placental separation and delivery occurs in <10 minutes. If the placenta is not detached within 30 minutes, the third stage of labor is considered prolonged. • Normal placental adherence is likely to be caused by the persistence of one of the placental inhibitory factors (nitric oxide or progesterone). Prior to the onset of labor, levels reduce; allowing placental detachment. Normal shearing, detachment, and expulsion are dependent on the contraction of the retroplacental myometrium. • Retained or adherent placental tissue prevents adequate contraction of the uterus and results in postpartum hemorrhage. – The succenturiate lobe of the placenta is usually the portion that is left behind. It is a small accessory lobe that is connected to the main part of the placenta by a blood vessel. – Trapping of detached placenta behind a closed cervix can also occur; but is less common – Variants of accreta where placental tissue is attached deep into the uterine wall can result in severe forms of retained placenta and blood loss. • Manual removal of the placenta is achieved by inserting a hand inside the uterus and separating the placenta from the uterine wall. – Uterotonics (oxytocin, methylergonovine) are administered before and/or after removal to stimulate contraction and prevent bleeding; uterine massage can also aid with contraction. – In the event that the placenta is trapped behind a closed cervix, uterolytics (nitroglycerine, volatile anesthetics) may be warranted, followed by administration of uterotonics after removal. – If retained placenta is difficult to remove and comes out in fragments, a curettage may be indicated to scrape the inside of the uterus to remove the fragments. – In placenta accreta, the removal of fragments may be difficult or impossible and require emergent hysterectomy and or ligation of bilateral iliac vessels. • Risk Factors – Previous retained placenta – Previous injury/scar to the uterus – Preterm delivery – Induced or augmented labor – Multiple gestation – Prior dilatation and curettage Position

Lithotomy position with legs resting on stirrups. Approximate Time

Ranges from 20 minutes to 1 hour for manual placental removal and D&C. EBL Expected

Ranges from mild (100 mL) to profound (2,000 mL or more) Hospital Stay

Depends on the severity of blood loss, concomitant organ dysfunction, and extraction procedure (e.g., hysterectomy versus uncomplicated manual extraction). Special Equipment for Surgery

• D&C instruments • Capability to proceed with hysterectomy • Set-up for invasive monitoring • Blood warmer • Rapid Infuser

EPIDEMIOLOGY Prevalence

At 30 minutes, the median rate of retained placenta was shown to be 2.67% in developed countries versus 1.46% in developing countries (1).

Prevalence

5–10% of major obstetric hemorrhage cases. More frequent among gestations <26 weeks compared to those >37 weeks. Morbidity

Related to the direct consequences of blood loss as well as the potential complications of hemostatic and resuscitative interventions. Mortality

Postpartum hemorrhage is potentially life-threatening. Data from retained placenta is not available. However, mortality is rare in developed countries due to early intervention and resuscitation. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess the severity of blood loss and optimize volume status, including the potential need for emergent blood transfusion. • The anesthetic plan should provide good analgesia with or without uterine relaxation. • Emergent hysterectomy or bilateral iliac vessel ligation are rare, but possible interventions.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Shortness of breath • Dizziness

History

• Placenta not expelled or partially expelled after delivery of the fetus • Estimated blood loss • Amount of crystalloids or blood transfused • Existing labor epidural

Signs/Physical Exam

• Pallor • Cold clammy skin • Dry mucus membranes and decreased skin turgor • Tachypnea • Tachycardia • Narrow pulse pressure • Poor capillary refill • Decreases urine output • Altered sensorium

MEDICATIONS

• Oxytocin • Methergine • Prostaglandins • Magnesium

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC, platelets; results may not be immediately available. • PT, PTT, fibrinogen; results may not be immediately available • Type and crossmatch • Ultrasound of the abdomen may be performed by the obstetric team to help evaluate the location of retained placental products. CONCOMITANT ORGAN DYSFUNCTION

• Coagulopathy may be due to severe blood loss and depleted clotting factors, or secondary to severe preexisting preeclampsia. • Oliguria and acute renal failure if severe blood loss. • Sheehan syndrome (hypopituitarism); during pregnancy, the pituitary gland is enlarged without a corresponding increase in blood supply. Second, the anterior pituitary is supplied by a low-pressure portal venous system. Major hemorrhage or hypotension during the peripartum period can result in ischemia of the affected pituitary regions leading to necrosis. The first sign is loss of lactation. Therapy requires hormone replacement. The posterior pituitary is usually not affected due to its direct arterial supply.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Aspiration prophylaxis may be considered, but should not delay induction in truly emergent procedures. Antacids may not be feasible in altered patients. • Fluid resuscitation • Blood transfusion if necessary

Special Concerns for Informed Consent

• Blood consent for potential transfusion • Potential to proceed with hysterectomy • Potential for postoperative intubation

INTRAOPERATIVE CARE Choice of Anesthesia

• Regional techniques allow the avoidance of airway instrumentation and may be considered in volume repleted and hemodynamically stable patients. – Spinal anesthetic may be appropriate in patients without an epidural catheter. It has the benefit of a fast onset, dense blockade, and definitive end-point (CSF) – Epidural catheter bolus may be appropriate if the patient has an existing, well-functioning epidural in place. • Minimal sedation and analgesia may be appropriate if the placenta is already separated and trapped by the closed cervix. • General anesthesia (GA) is recommended if bleeding is excessive, the patient is hypovolemic, there is no well-functioning epidural in situ, uterine instrumentation is needed, placenta accreta has been diagnosed, or a hysterectomy is strongly possible. Monitors

• Standard anesthesia monitoring • Foley catheter to measure urine output and aid in the assessment of urine output • Consider invasive monitoring with an arterial line or CVP line if significant bleeding and unstable vitals. Induction/Airway Management

• Spinal anesthetic should be dosed to achieve a T10 sensory level. • Epidural “topping off” is performed with a local anesthetic. Consider one with a quick onset such as chloroprocaine, mepivacaine, and lidocaine (with bicarbonate). Goal of a T10 sensory level. • Sedation and analgesia should be titrated to effect. This can result in transient hypotension. • GA should be induced with a rapid sequence induction – Cricoid pressure should be applied and suction readily available. – Ketamine as an induction agent may be considered if the patient is hemodynamically unstable.

– Pregnant women have an increased risk of difficult airways; be prepared with special intubating devices as appropriate.

Maintenance

• Uterolytic administration. Be aware of potential side-effects – Oxytocin: hypotension (increased when administered as a rapid IV bolus), water intoxication, uterine rupture – Ergometrine: nausea, vomiting, abdominal pain, hypertension, cardiac arrhythmias – Prostaglandins: bronchospasm, increased pulmonary vascular resistance • Uterolytics are utilized when the placenta is trapped behind a closed cervix. – Nitroglycerin is commonly used. IV dosing is rapid in onset (within 60 seconds) and short in duration (60 seconds); there are minimal hemodynamic effects at doses of 50 μg. SL dosing is also rapid in onset (35–65 seconds); 2 sprays of 0.4 mg for a total of 0.8 mg. May cause hypotension, especially in hypovolemic patients. – Inhalational agents provide good uterine relaxation at concentrations >1 MAC, but may result in hypotension.

Extubation/Emergence

• Extubation should occur after the patient is awake, fully reversed, has good respiratory effort, and regained protective airway reflexes. • Consider leaving the patient intubated when hemodynamically unstable or in DIC.

FOLLOW-UP BED ACUITY

• Vigilance for bleeding • Consider supplemental oxygen with nasal cannula or face mask as appropriate

ANALGESIA

• Pain is typically mild and PO opioids are often sufficient. • If the patient had a hysterectomy, analgesia may be provided with neuraxial opioids or PCA. • Epidural catheters should be removed only after documenting normal coagulation status when bleeding was significant.

COMPLICATIONS

• Perforation of the uterus may result from manual exploration of the uterus or curettage. • Laparotomy and possible hysterectomy may be necessary if other techniques are unsuccessful or a placenta accreta is present. • Hemorrhage can result in hypotension and the need for blood transfusion; may be necessary to administer type O uncrossmatched blood. • Complications due to blood transfusion (TRALI) and excess fluid resuscitation (pulmonary edema) • Infection

REFERENCES

1. heung WM, Hawkes A, Ibish S. The retained placenta: Historical and geographical rate variation. J Obstet Gynaec. 2011;31(1):37–42. 2. Leduc D, Senikas V, Lalonde AB, et al. Active management of third stage of labor: Prevention and treatment of postpartum hemorrhage. J Obstet Gynaecol Can. 2009;31(10):980–993. 3. Mercier FJ, Van de Velde M. Major obstetric hemorrhage. Anesthesiology Clin. 2008;26(1):53–66.

4. Ahonan J, Stefanovic V, Lassila R. Management of post-partum haemorrhage. Acta Anesthesiol Scand. 2010;54(10):1164–1178. See Also (Topic, Algorithm, Electronic Media Element) • Postpartum hemorrhage • Hysterectomy

CODES ICD9 • 666.02 Third-stage postpartum hemorrhage, delivered, with mention of postpartum complication • 666.04 ICD10 • O72.0 Third-stage hemorrhage • O73.0 Retained placenta without hemorrhage

CLINICAL PEARLS

• Management of a retained placenta should be active. • Uterotonics are the first line of treatment; however, uterolytics may be required when the placenta is retained behind a closed cervix. • Check volume status and estimated blood loss. May require aggressive resuscitation with fluids and blood. • Avoid spinal anesthetic in the presence of profound hypotension and inadequate fluid resuscitation.

RETINAL DETACHMENT Gundappa Neelakanta, MD Allen Hu, MD

BASICS DESCRIPTION General

• Retinal detachment (RD) is a condition in which the retina is separated from the underlying retinal pigment epithelium (RPE) accompanied by the collection of subretinal fluid. The cells of the nerve tissue are isolated from their supplies of nourishment and can die, leading to a loss of vision. There are four types of RD: – Rhegmatogenous (“rhegma” = tear) detachments occur when fluid from the vitreous cavity flows through a retinal tear and dissect underneath the retina, causing detachment from the wall of the eye (most common). Tears are either triangular or circular. – Tractional detachments occur when scar tissue from inside the eye contracts and pulls the retina away from its attachment to the wall of the eye (more common in diabetics). – Exudative or serous detachments occur when fluid collects in the normally closed space from uveitis or choroid tumor. Unlike rhegmatogenous detachments, the fluid does not come through a tear in the retinal tissue. – Combined tractional/rhegmatogenous detachments • RD is a common ophthalmic emergency that may require urgent surgery to prevent blindness. Principles of surgical repair involve identification and treatment of causes and the recreation of a firm adhesion (pneumatic retinopexy and/or scleral buckle) between the retina and the wall of the eye. – Tears are treated by promoting adhesion between the outer retinal layers and RPE with diathermy, cryotherapy, laser endophotocoagulator, or indirect laser photo coagulator. Note: Tears may occur without detachment and may be treated in the office setting when discovered to prophylact detachment. – A scleral buckle is a silicone band or sponge that is sutured and tightened to the sclera to indent it toward the detached retina and establish contact between the retina and retinal pigment layer. This promotes closure of breaks and decreases the effects of traction and other factors responsible for RD. – Vitrectomy involves operating on the retina from within the eye. Three small incisions are made to allow for infusion of fluid into the eye, insertion of a fiberoptic light source, and insertion of an instrument (microscissors, forceps, knife, or vitrector). The instrument is used to remove the vitreous gel under the eye, followed by a pneumatic retinopexy (injection of gas or air intravitreally to flatten the retina from inside). The tamponading agent is typically a gas such as sulfur hexafluoride (SF6) or perfluoropropane (C3F8) that

may remain in the eye for as long as 6 weeks. If a more permanent endotamponade is necessary, silicone oil may be used. Patients may require another surgery in the future to

remove the silicone oil. • After RD surgery, patients may need to maintain the head in a certain position to ensure the endotamponade agent is positioned against the retinal break.

Position

• Supine with the head typically immobilized (tape over the forehead), nonoperative eye covered with a shield, and whole face and body draped • Access to the airway is limited.

Incision

Access to the eyeball through an incision in the lower or lateral conjunctiva. Approximate Time

Variable; 1–3 depending on position and extent of RD and the combination of procedures required (scleral buckle, vitrectomy, injection of gas bubble, laser, cryopexy or cautery). EBL Expected

Minimal and typically insignificant Hospital Stay

Most patients are discharged home the same day from the recovery room. Inpatient stay is rarely required. Special Equipment for Surgery

Specialized pars plana vitrectomy machine with wide angle viewing systems, laser, cryopexy, and diathermy EPIDEMIOLOGY Prevalence

• It is relatively uncommon with an annual incidence of ∼36,000 in the US. Estimated incidence of 12 in 100,000 in the general population with an annual risk of 0.01%, and lifetime risk of 0.6%. • RD is more common with aging as the vitreous gel begins to develop pockets of liquefaction. As these pockets become more numerous, they combine to form larger pockets and can break away from the retina. Once the seal is compromised, the structures “peel” away from each other.

Morbidity

• Worsened prognosis when affects the macula. • Considerable morbidity due to loss of vision or decreased visual acuity.

Mortality Rare

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Emergency surgery is rarely indicated. Most surgeries are performed within 24 hours if the

macula is “on” (macula spared) or within 7 days if the macula is “off” (macula involved). • A retrobulbar block (or general anesthesia) can provide a still patient with immobility of the eye and analgesia or anesthesia. • If general anesthesia is used, smooth induction and emergence are critical to avoiding increases in intraocular pressure. • Long-acting gas such as SF6 and C3F8 may be injected for treatment of RD. Use of nitrous

oxide in these patients is contraindicated both intraoperatively and postoperatively for up to 6 weeks. Animal experiments show that the intraocular pressure can double in about 25 minutes with the use of 75% nitrous oxide; this may result in retinal artery occlusion, retinal ischemia, and eventual vision loss. Although intracavitary dwell time of these gases is about 28 days, permanent vision loss has occurred with the use of nitrous oxide as late as 6 weeks following surgery.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Floaters and light flashes are not due to RD but can occur. • Visual acuity may be normal if the macula is not involved. Central visual field and visual acuity is affected in the presence of macular involvement.

History

• Patients with high myopia, cataract surgery, severe ocular trauma, ocular infections, lattice degeneration, and glaucoma are at higher risk for development of rhegmatogenous retinal detachment (RRD). • Lattice degeneration is the most common cause of vitreoretinal degeneration. The risk of RD with lattice degeneration increases in association with the degree of myopia. • Patients present with painless loss of vision • Traumatic RD involves a history of direct trauma to the eye.

Signs/Physical Exam

• Direct or indirect ophthalmoscopic examination, aided by scleral depression, shows an opaque, elevated, corrugated retina that freely undulates with eye movement. • Retinal tears are often multiple.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

Significant media opacities, such as hyphema (blood in anterior chamber) or vitreous hemorrhage as a result of trauma, can preclude direct examination of the retina. A B-scan ultrasound examination may be needed to rule out RD. CONCOMITANT ORGAN DYSFUNCTION Usually none

TREATMENT PREOPERATIVE PREPARATION Premedications

• Patients are generally anxious secondary to the anticipated operation on the eye, postoperative pain, and visual outcomes. • Detailed explanations, assurance of analgesia, and midazolam IV may help alleviate the anxiety. Special Concerns for Informed Consent

Difficulty reading the written informed consent forms. Antibiotics/Common Organisms

Systemic antibiotics are not usually required. Antibiotics are injected into the conjunctiva at the end of surgery. INTRAOPERATIVE CARE Choice of Anesthesia

• Most procedures are performed under regional anesthesia via either a retrobulbar or peribulbar block. – A retrobulbar block provides adequate analgesia and akinesia of the ocular muscles. Complications (rare) include risk of globe perforation especially in patients with high myopia; retrobulbar hemorrhage; or injection into the CSF via the dural sheath around the optic nerve, resulting in apnea, hypotension, and bradycardia. Treatment involves hemodynamic support and ventilation until the effects of local anesthesia are terminated, usually in a few hours. – Peribulbar blocks have fewer complications, but may provide inadequate anesthesia. Supplemental topical anesthesia is frequently required, especially toward the end of a prolonged surgery. • General anesthesia may be chosen due to patient preference, extent of planned surgery, or surgeon’s preference. Monitors

• Standard ASA monitors and neuromuscular twitch monitor during general anesthesia. • Invasive monitors are rarely required given minimal hemodynamic perturbations but are dictated by the patient’s underlying medical status. Induction/Airway Management

• Retrobulbar block is usually performed by inserting a needle above the inferior orbital rim. After passing the equator of the globe, the needle is redirected cephaladly toward the apex of the orbit. Length and gauge of the needle, choice of local anesthetic drug, and volume vary. The use of additional supplemental drugs also varies. • Retrobulbar or peribulbar block is performed under monitored anesthesia care (MAC). A variety of anesthesia drugs, such as propofol, alfentanil, remifentanil, or fentanyl, may be

used alone or in combination to provide sedation during the block. The goal is to provide adequate sedation, amnesia, and analgesia for injection without significant cardiorespiratory depression. • Consider full stomach or other associated injuries if the RD is due to eye trauma. Most patients can be scheduled to avoid full stomach precautions. • If general anesthesia is indicated, plan for a smooth induction to avoid coughing and bucking. Endotracheal intubation is safest for airway management.

Maintenance

• MAC can be provided with a number of intravenous agents. Avoid oversedation with resultant hypoxia, hypercarbia, and inability to follow commands • General anesthesia is maintained with a choice of inhalational agent in oxygen and air; avoid the use of nitrous oxide. However, if used, nitrous oxide needs to be turned off for 20–30 minutes prior to the injection of intraocular gas. • Supplemental analgesia may be provided by titrating small doses of fentanyl or longer acting opioids (also provides postoperative analgesia). • Complete neuromuscular paralysis, with monitoring of neuromuscular function, helps avoid unintentional movement of the patient during surgery under general anesthesia. • Antiemetics should be given prophylactically to prevent nausea and vomiting as they can increase intraocular pressure.

Extubation/Emergence

• A local anesthetic, usually bupivacaine, may be injected or instilled into the retrobulbar space at the end of surgery under general anesthesia to provide postoperative analgesia. • Coughing and bucking on the endotracheal tube should be avoided during extubation. Deep extubation may be achieved by a combination of techniques using inhalational or IV anesthesia, or instillation of lidocaine via the endotracheal tube.

FOLLOW-UP BED ACUITY

No special monitoring is required. However, patients may be instructed to maintain their head in a certain position (e.g., head down) as soon as possible, which may interfere with airway protection and oxygenation. They are usually discharged home from the recovery room after all criteria for discharge are met. ANALGESIA

Postoperative analgesia is usually adequate with combined oral codeine/acetaminophen medications for 24 hours. Severe pain may require evaluation by the ophthalmologist. COMPLICATIONS

• Scleral buckle: Choroidal or retinal incarceration, suprachoroidal or subretinal hemorrhage, strabismus and diplopia, worsening of myopia, late extrusion, and infection of buckle. • Vitrectomy and pneumatic retinopexy: Induced cataract, glaucoma, retinal trauma, optic nerve trauma, intraocular bleeding.

• Rare cases of venous air embolism have been reported during air/fluid exchange.

PROGNOSIS

With appropriate surgical intervention, anatomic success rates of 90–95% can be achieved; nonetheless up to 40% of treated patients have visual acuity of 20/50 or worse. Postoperative visual acuity is adversely affected by preoperative involvement of the macula and longer duration of RD. It is also adversely affected by macular edema and formation of macular pucker.

REFERENCES

1. Brucker AJ, Hopkins TB. Retinal detachment surgery: The latest in current management. Retina. 2006;26(6 Suppl):S28–S33. 2. D’Amico DJ. Primary retinal detachment. N Engl J Med. 2008;359:2346–2354. See Also (Topic, Algorithm, Electronic Media Element) • Oculocardiac reflex • Total spinal • Local anesthetic systemic toxicity

CODES ICD9 • 361.00 Retinal detachment with retinal defect, unspecified • 361.81 Traction detachment of retina • 361.9 Unspecified retinal detachment ICD10 • H33.009 Unsp retinal detachment with retinal break, unspecified eye • H33.20 Serous retinal detachment, unspecified eye • H33.40 Traction detachment of retina, unspecified eye

CLINICAL PEARLS

• Most cases of RD require surgery. However, urgent surgery is rarely required and most cases can be delayed for adequate preoperative evaluation and preparation. • Long-acting gases such as sulfur hexafluoride or perfluoropropane, may be injected into the intravitreous cavity for tamponade. Use of nitrous oxide in these patients is contraindicated both intraoperatively and postoperatively for up to 6 weeks. • Further, the above gases may be injected in an office setting (pneumopexy) for retinal tears under local anesthesia. Elicitation of such a history is important if these patients present for surgery unrelated to the eye.

RETINOPATHY OF PREMATURITY (ROP) Amitabh Goswami, DO, MPH

BASICS DESCRIPTION

• Retinopathy of prematurity (ROP) describes the abnormal development of retinal vasculature in preterm infants that can result from oxygen therapy; formerly known as retrolental fibroplasia. • It remains the most common cause of childhood blindness in the US. • Anesthesia providers are often involved in providing care to patients presenting for ophthalmic procedures. In addition, in premature patients who present for unrelated surgery, a clear understanding of the pathogenesis along with appropriate preventive measures may reduce the incidence of this unfortunate disease. EPIDEMIOLOGY Prevalence

In patients diagnosed with ROP, the severe form comprises 36% of cases. Prevalence

• 8% in infants >32 weeks • 19% in infants 27–31 weeks • 43% in infants <27 weeks

ETIOLOGY/RISK FACTORS

• Prematurity: <1,000 g, <29 weeks gestation • Infant comorbidities and treatment – Hypoxia/hyperoxia – Apnea/bradycardia – Hypercapnia/hypocapnia – Asphyxia/acidosis/shock – Anemia requiring blood transfusions – Sepsis – Intraventricular hemorrhage and seizures – Nutritional deficiency – Bilirubinemia requiring phototherapy – Ventilator support – Surfactant therapy • Pregnancy complications that predispose to prematurity include: – Hypertension – Diabetes – Bleeding

– Smoking

PHYSIOLOGY/PATHOPHYSIOLOGY

• ROP develops in two main stages: Hyperoxia followed by hypoxia of the retinal vasculature. • The hyperoxic stage. Normal vascularization is affected and vessel growth ceases. Because of the high rate of blood flow to the choroidal circulation, the retina is particularly affected. • The hypoxic phase follows. Normal photoreceptor development requires high levels of oxygen. However, the abnormal, underdeveloped retinal vasculature (secondary to hyperoxia) cannot meet oxygen demands. Consequently, hypoxia-inducible factor and vascular endothelial growth factor are released and stimulate “neovascularaization" with abnormal proliferation from the retina to the vitreous. Neovascularization can cause fluid leak, hemorrhage, and retinal scar formation with traction of the retina. In severe cases, traction can lead to detachment and blindness. • Progression. Spontaneous recovery is seen in up to 85% of cases, with mild ROP having the most favorable prognosis (usually regresses in 2–3 months). Moderate ROP may resolve in 6 months; however, severe ROP can result in blindness or limited vision. • Fetal prematurity is also associated with hyaline membrane disease (60–80%). • Exposure to high FiO2 while in utero does not result in ROP due to hemoglobin F. • Classification strategies based upon opthalmoscopic findings at the junction of the vascular and avascular retina: – STAGE 1: Demarcation line – STAGE 2: Ridge formation – STAGE 3: Ridge with extraretinal fibrovascular proliferation – STAGE 4: Sub-total retinal detachment – STAGE 5: Retinal detachment – Rush disease: Rapid progression (days) to severe ROP and retinal detachment – Plus disease: Dilation and tortuosity of arterioles and venules in the posterior pole.

PREVENTATIVE MEASURES

• Elective or outpatient procedures should be deferred until the preterm infant reaches at least 50 weeks postconceptual age. • Noninvasive spectrophotometric retinal oximeters have improved the ability to regulate oxygen tensions. Previously, the lack of noninvasive techniques to measure retinal oxygen tension or saturation of retinal blood vessels obligated clinical decisions to be based on arterial measurements alone. • Perioperatively, however, preventive measures include minimizing oxygen administration while avoiding arterial hypoxemia: – Maintain PaO2 between 60 and 80 mm Hg – Maintain the SaO2 between 92% and 96%

PREOPERATIVE ASSESSMENT • All premature infants with birth weights <1,200–1,700 g should be screened at 4–6 weeks. • Larger premature infants should be screened if oxygen therapy exceeds 50 days.

• Early pediatric ophthalmologist consultation. • History. An ophthalmic history with attention to birth history, birth weight, birth trauma, asphyxia, maternal drug history, cardiovascular and respiratory status. – Signs and exam may reveal a shallow anterior chamber, corneal edema, iris atrophy, poor papillary dilation, leukocoria (white pupils), vitreous hemorrhage, nystagmus, strabismus, retrolental fibroplasias, and retinal detachment.

TREATMENT Peripheral retinal ablation can be accomplished with

• Laser therapy (treatment of choice) allows for deep tissue penetration, is minimally invasive, and can be less painful than other modalities. • Cryotherapy freezes abnormal retinal tissue. However, it requires general anesthesia, is more painful, and expensive. • Scleral buckle and vitrectomy may be needed for retinal detachment. • Other treatment modalities include – Exogenous rHuEPO (erythropoietin) – Intravitreal injection of bevacizumab has been reported as a supportive measure in aggressive ROP. – Serum IGF-1 from breast milk or exogenous IGF-1. – Maintaining serum glucose <120 mg/dL. – Treatment of anemia with a liberal transfusion policy. – Photopic adaptation by adjusting illumination and retinal oxygen consumption can be reduced. – Vitamin E supplements – Omega-3 supplements

FOLLOW-UP • Initial exam between 31 and 32 weeks postconceptual age. • Follow-up exam every 1–2 weeks until the periphery is vascularized, then monthly exams. • Parents must be taught to care for their blind or visually impaired child. • Referrals to PT, OT, and agencies for the blind to help families avoid developmental delays.

REFERENCES

1. Good WV. Retinopathy of prematurity and the peripheral retina. J Pediatr. 2008;153(5):591–592. 2. Jussain N, Clive J, Bhandari V. Current incidence of retinopathy of prematurity, 1989– 1997. Pediatrics. 1999;104:e26. 3. Quinn GE. International classification of retinopathy of prematurity. The Committee for the Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123:991– 999.

4. Phelps DL. ETROP Cooperative Group. The early treatment for retinopathy of prematurity study: Better outcomes, changing strategy. Pediatrics. 2004;114(2):490–491. 5. journalofpediatricophthalmology.com An Epidemiological Analysis of Retinopathy of Prematurity Over Ten Years. See Also (Topic, Algorithm, Electronic Media Element) • Anemia of prematurity • Fetal cardiovascular physiology • Retinal detachment surgery • Oxygen toxicity

CODES ICD9 362.20 ICD10 • H35.101 Retinopathy of prematurity, unspecified, right eye • H35.102 Retinopathy of prematurity, unspecified, left eye • H35.109 Retinopathy of prematurity, unspecified, unspecified eye

CLINICAL PEARLS

• The incidence and severity of ROP increases with decreasing gestational age and birth weight. • Fetal hemoglobin (HbF) may protect against ROP. • Prevention of ROP ultimately depends on the prevention of premature birth. • Anesthesia providers should avoid the administration of “hyperoxic" gases to patients at risk for ROP. Furthermore, these patients also pose a challenge, as their associated comorbidities may have competing interests (increased need for oxygen delivery).

RETROPHARYNGEAL AND PERITONSILLAR ABSCESS Dam-Thuy Truong, MD Angela Truong, MD

BASICS DESCRIPTION General

Deep neck space infections encompass a wide range of clinical severity. • In the early period, diffuse cellulitis can usually be treated with antibiotics. • In the late period, if the retropharyngeal and peritonsillar abscesses are left untreated the suppurative collections may rapidly expand to the mediastinum, carotid sheath, and base of the skull or cause lethal airway obstruction. Position

• Supine; head elevated 20° • OR table straight or turned 90–180°

Incision

Intraoral

Approximate Time 60–120 minutes EBL Expected 50–150 mL

Hospital Stay 3–5 days

Special Equipment for Surgery

Cricothyrotomy set and tracheostomy sets opened and ready for use in the OR EPIDEMIOLOGY Prevalence

• Peritonsillar abscess in adolescents and adults: 30 per 100,000 • Retropharyngeal abscess is most common in pediatric patients age 6 months to 6 years (mean age 3–5) Prevalence

Increased in low socioeconomic status and/or those with chronic oral, dental, and respiratory infections due to poor oral hygiene or inadequate health care

Morbidity

Related to hospitalization, surgical procedures, general anesthesia, and potential complications Mortality

Overall mortality 1–2.6%. Results from: • Airway obstruction with progression of edema and airway manipulation during attempts to secure the airway • Invasion or rupture into neighboring structures (Carotid sheath). Septic mediastinitis has a 50% mortality.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Meticulous planning and cooperation between the anesthesia provider and otolaryngologist must be maintained throughout the case. • All necessary equipment for airway management should be ready in the operating room, including a variety of laryngoscopes, different sized endotracheal tubes (ETTs), laryngeal mask airways (LMA), fiberoptic bronchoscopes, jet ventilation equipment, and tracheostomy sets. • Despite the severity of the situation, airway control should be done meticulously, gently, and patiently. – Maintain spontaneous ventilation until after successful intubation: Avoid sedatives, hypnotics, and muscle relaxants. – Maintain airway patency: Avoid airway trauma causing complete airway obstruction. – If unsuccessful, discontinue fiberoptic intubation (FOI) attempts and proceed to tracheostomy before complete airway obstruction or respiratory arrest occurs.

PREOPERATIVE ASSESSMENT SYMPTOMS

Fever, malaise, irritability, lethargy, sore throat, dysphagia, odynophagia, difficulty breathing History

Recent URI, trauma to neck or oral cavity (head and neck surgery, dental procedure), immunosuppressed state Signs/Physical Exam

• Toxic appearance, febrile, trismus, neck swelling, torticollis, decreased neck range of motion, nuchal rigidity, retropharyngeal bulge • Tachypnea and stridor indicate impending airway obstruction. • Hemorrhage from ear, nose, or mouth signals carotid artery rupture.

MEDICATIONS

• Antibiotics • Dexamethasone

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC: Elevated WBC (range 3,100–45,000/microliter with a mean of 17,000/microliter). A normal count does not rule out retropharyngeal abscess since 18% of patients have a WBC <8,000/microliter. • Throat culture; aspirated pus for Gram stain, culture, and sensitivity; blood culture • CT scan of neck: Hypodense lesion in the retropharyngeal space with peripheral ring enhancement, soft tissue swelling, and mass effect • Lateral neck x-rays: Swelling of the posterior pharyngeal wall is diagnostic for retropharyngeal abscess. • Nasopharyngoscopy is performed with topical anesthesia to the nasopharynx and can help assess airway edema upon initial presentation and can be done periodically for ongoing airway evaluation. CONCOMITANT ORGAN DYSFUNCTION

Septic shock and multiorgan system failure (acute renal failure and adult respiratory distress syndrome)

TREATMENT PREOPERATIVE PREPARATION Premedications

• Avoid sedatives in potential airway compromise • Anticholinergics to help decrease secretions • Steroids to help decrease edema • Fluid resuscitation for dehydration • Initiate antibiotics treatment

Special Concerns for Informed Consent

• Pediatric cases require consent from parents • Potential for a surgical airway

Antibiotics/Common Organisms

• Aerobes, anaerobes, Gram-negative organisms, and/or mixed flora. • IV broad-spectrum antibiotics: Clindamycin and metronidazole – Adult: Clindamycin 600–900 mg IV q8h with metronidazole 1 g IV load followed by 500 mg q6h – Child: Clindamycin 25–40 mg/kg/d IV divided q6–8h with metronidazole 30 mg/kg/d divided q8h

INTRAOPERATIVE CARE Choice of Anesthesia

• Local anesthesia for needle aspiration

• General anesthesia for incision and drainage

Monitors

• Standard ASA monitors • Arterial line in cases with – Anticipated large blood loss – High risk of perioperative airway compromise – Severe comorbidities

Induction/Airway Management

• The choice of techniques to secure the airway must be carefully individualized, depending on anticipated difficulties and the expertise and skills of the anaesthetist and otolaryngologist in charge. • A routine induction, laryngoscopy, and intubation may be considered in the following circumstances: – Early diagnosis – Minimal neck edema – No trismus – Normal airway with no special risk for difficult ventilation and intubation • Inhalation induction with oxygen and sevoflurane may be carefully and deliberately performed in young children who cannot cooperate for awake fiberoptic bronchoscopy or tracheostomy. – Maintain spontaneous respirations with gentle manual CPAP to prevent airway collapse and inflation of the stomach – Intubate only after an adequate depth of anesthesia is achieved to prevent laryngospasm – Use a smaller ETT than usual because of the potential for edema of the airway • Awake FOI should be performed in cooperative patients with the potential for airway compromise. It requires judicious topicalization of the airway with local anesthetic. – All the steps of the procedures should be clearly explained to the patient to gain complete cooperation. – Because of copious secretions, pretreatment with anticholinergics may be needed and it may take longer to achieve optimal conditions for intubation. – Localization of the glottic opening may be facilitated by delivering high flows of oxygen through the fiberoptic bronchoscope to disperse secretions, or compression of the chest wall to create air bubbles coming from the larynx. – A small and well-lubricated LMA may be inserted gently to help focus on the larynx and help in the guidance of the fiberoptic bronchoscope armed with an Aintree catheter to successfully intubate the trachea. • Awake tracheostomy should be performed by an experienced otolaryngologist when extreme anatomical airway distortion is present. – Generally considered the gold standard in securing these difficult airways – Severe neck swelling and inability of the patient to lie supine requires a very experienced otolaryngologist to achieve success under these difficult conditions.

Maintenance

Standard maintenance for general anesthesia with the use of short-acting, easily reversible agents Extubation/Emergence

• Extubate when fully awake • Keep intubated postoperatively if airway edema persists

FOLLOW-UP BED ACUITY

• Postanesthesia care unit • Intensive care unit if the patient is to remain intubated

ANALGESIA

Careful titration of opioid analgesic drugs or NSAIDs as appropriate COMPLICATIONS

• Intraoperative loss of airway control; accidental extubation • Massive hemorrhage • Severe supraglottic and glottic edema

PROGNOSIS

Excellent in patients without serious comorbidities

REFERENCES

1. Ho AM, Chung DC, To EW, et al. Total airway obstruction during local anesthesia in a nonsedated patient with a compromised airway. Can J Anesth. 2004;51(8):838–841. 2. McGuire G, El-Beheiry H, Brown D. Loss of the airway during tracheostomy: Rescue oxygenation and re-establishment of the airway. Can J Anaesth. 2001;48(7):697–700. 3. Ovassapian A, Tuncbilek M, Weitzel E, et al. Airway management in adult patients with deep neck infections: A case series and review of the literature. Anesth Analg. 2005;100(2):585–589. 4. Parhiscar A, Har-El G. Deep neck abscess: A retrospective review of 210 cases. Ann Otol Rhinol Laryngol. 2001;110(11):1051–1054. 5. Potter JK, Herford AS, Ellis E III. Tracheostomy versus endotracheal intubation for airway management in deep neck space infections. J Oral Maxillofac Surg. 2002;60(4):349–354. See Also (Topic, Algorithm, Electronic Media Element) • Trismus • Difficult airway • Laryngospasm

CODES

ICD9

• 475 Peritonsillar abscess • 478.24 Retropharyngeal abscess ICD10

• J36 Peritonsillar abscess • J39.0 Retropharyngeal and parapharyngeal abscess

CLINICAL PEARLS

• Avoid blind nasotracheal intubation, rigid direct laryngoscopy, and rigid fiberoptic stylets due to their low success rates and high risk of serious complications. • FOIs – Do not attempt FOI in cases of impending complete airway obstruction; proceed directly to awake tracheostomy. – Secretions and tissue edema can present barriers to effective topicalization. To that extent, supplement by spraying the airway with local anesthetic through the fiberoptic bronchoscope. – Limit the number of FOI attempts; if unsuccessful, proceed to tracheostomy before airway obstruction or respiratory arrest occurs. • Back up plans/safety precautions – Before starting the FOI, it is prudent to have the surgeon examine the neck and mark the site for tracheostomy in the event that an emergent surgical airway needs to be performed. Consider prepping the site. – Prior to beginning airway manipulation, a cricothyroid puncture with a 14 g angiocatheter may be inserted to facilitate jet ventilation in the case of a dire emergency. – Have available a rescue emergency ventilatory support plan in case both FOI and tracheostomy attempts are unsuccessful: LMA, cricothyrotomy, jet ventilation.

RH FACTOR

Natesan Manimekalai, MD

BASICS DESCRIPTION

• Rh (“Rhesus factor”) is a glycoprotein with antigenic properties that can be present on red blood cell (RBC) membranes. Individuals – With Rh antigen are denoted Rh positive (or their blood type followed by a positive; for example, A+, B+, AB+, O+) – Without Rh antigen are denoted Rh negative (or their blood type followed by a negative; for example, A−, B−, AB−, O−) • In 1940, Drs. Karl Landsteiner and Alexander S. Wiener described an antiserum that was produced by immunizing rabbits with RBCs from Rhesus macaque; it agglutinated about 85% of human RBCs. The antigen that induced this immunization was named Rh factor to indicate that Rhesus blood was the donor for the production of the serum PHYSIOLOGY PRINCIPLES

• The Rh blood group is the second most immunogenic and clinically significant blood group system after ABO. • The Rh blood group system consists of more than 45 antigens, among which the D, C, c, E, and e are most important. • Agglutinins (antibodies) develop spontaneously in the plasma to the ABO blood group system, whereas antibodies to the Rh system are produced either through blood transfusion or placental transfer from the fetus during pregnancy. • Rh antigen is determined as follows – Homozygous Rh positive, antigen DD (Rh+) – Heterozygous Rh positive, antigen Dd (Rh+) – Homozygous Rh negative, antigen dd (Rh–) • D antigen is wildly prevalent and more antigenic in the population than E or C. However, even in Rh negative individuals, E and C antigens may present and can cause a mild transfusion reaction.

ANATOMY

The genes encoding the Rh proteins (RHD) are present on the short arm of chromosome 1. PHYSIOLOGY/PATHOPHYSIOLOGY

• Rh incompatibility – Low incidence in the general population. – When an Rh negative person receives Rh positive blood, anti-Rh agglutinins develops slowly over a period of 6 weeks to 4 months. – The slow development of Rh antibody will not produce any immediate transfusion

reactions on first exposure. However, should the same person be exposed to Rh positive blood a second time, there will be an enhanced transfusion reaction against the transfused RBCs (hemolysis occurs at a slower rate compared to acute hemolytic reactions from ABO incompatibility). • Hemolytic disease of the newborn (HDN) – A serious and potentially fatal disease produced by hemolysis of Rh positive fetal RBCs. When an Rh negative mother becomes pregnant with an Rh positive baby, the fetal Rh positive RBCs enter the maternal circulation during delivery and initiate an immune response in the mother. In subsequent pregnancies, the Rh antibodies enter the fetal circulation through the placenta. If the second baby is also Rh positive, then these antibodies lyse the fetal blood cells. – Severity: Can range from mild (fetus is minimally anemic) to moderate and severe (profoundly anemic and an excessive amount of bilirubin will be produced). In extremely severe conditions, the fetus develops erythroblastosis fetalis that is characterized by ascites, edema, pleural and pericardial effusions, high output cardiac failure, and extramedullary hematopoiesis. – Fetal bilirubin: Transported to the mother through the placental circulation and metabolized by the maternal liver. Immediately after the birth, the excess bilirubin cannot be metabolized by the immature fetal liver and the baby becomes extremely jaundiced. The excess bilirubin crosses the blood–brain barrier and reaches the CNS and produces a condition called kernicterus. Kernicterus is characterized by the loss of reflexes, posturing, inactivity, poor feeding, bulging fontanelles, and seizures. Later, the infant may develop hearing loss, and mental retardation.

PERIOPERATIVE RELEVANCE

• RBCs. ABO and Rh compatibility should be performed and confirmed prior to any blood transfusion. In an emergency situation, patients should receive O Rh Negative blood (O−). Men and postmenopausal women may receive O+ blood. • Fresh-frozen plasma (FFP). ABO compatibility is preferred, but may not be necessary in an emergency. Because FFP may contain only a small amount of RBCs, sensitization to Rh is unlikely; thus, donor FFP may be administered regardless of the recipient’s Rh status. No prophylaxis is typically required; however, if administered to a woman of childbearing potential, there is some evidence to support prophylaxis. • Platelets. Platelets possess ABO antigens, but not Rh. ABO and Rh typing are not necessary, but incompatibility can decrease post-transfusion counts (mainly from ABO incompatibility). Because platelets contain only a small amount of RBCs, sensitization to Rh antigen is unlikely; thus, donor platelets may be administered regardless of the recipient’s Rh status. No prophylaxis is typically needed; however, if administered to a woman of childbearing potential, there is some evidence to support prophylaxis. • Cryoprecipitate. ABO compatible units are preferred when large volumes are needed; however, Rh compatibility does not appear to be necessary. • Rh incompatibility following blood transfusion in the general population creates difficulties in finding future compatible donors. • Risk factors for Rh isoimmunization during pregnancy.

– Spontaneous abortion – Placenta previa – Placental abruption – Ectopic pregnancy – Abdominal/pelvic trauma – Intra uterine fetal death – Amniocentesis – Cordocentesis – Chorionic villous biopsy – Routine pregnancy • Rh typing is performed in every pregnant patient via a serum blood draw. If the mother is Rh negative, Rh typing is performed on the father. • Fetal Rh typing can be done from amniocentesis or chorionic villus sampling (CVS). • In Rh negative mothers with a second Rh positive fetus, serial measurements of maternal antibody titers are performed during pregnancy. Additionally, frequent ultrasonography is performed to monitor the fetal well-being and to detect anemia and signs of hydrops, like the diameter of the umbilical vein, placental thickness, and pericardial effusion. • Color-flow Doppler: Measuring the peak systolic middle cerebral artery (MCA) velocity by ultrasound has proved to be a reliable method to detect fetal anemia. Peak systolic velocity is measured by using the pulsed Doppler. Measurements can be started as early as 18 weeks of gestation and are to be repeated at 1- to 2-week intervals until 35 weeks. • Anti-D IgG prophylaxis coats and destroys Rh positive fetal cells when they enter the maternal circulation, thereby preventing maternal sensitization. It is administered in the following situations – Rh incompatible transfusion in women with childbearing potential – Rh negative mothers with an Rh positive fetus (regardless of antibody levels). It is given as either a single injection of 300 μg IM (1,500 UI) at the 28th week of gestation or two injections of 100–125 μg (500–625 UI), at the 28th week and 34th week of pregnancy. Additionally, because the half-life of IgG is 17–21 days, an additional 300 μg is administered within 72 hours of delivery. Prophylaxis does not appear to have any side effects on the fetus and can decrease the risk of alloimmunization of an Rh negative gravid women to 0.2% during that pregnancy, as well as the probability of immunization in subsequent pregnancies. – As a “booster” dose in Rh negative mothers with an Rh positive fetus Threatened abortion Hydatidiform mole Ectopic pregnancy Fetal death Blunt trauma to the abdomen Placenta previa Placental abruption Amniocentesis External cephalic version. • Fetal intraperitoneal blood transfusions are considered to correct fetal anemia and prevent

hydrops fetus. It involves delivering blood (fresh, packed, Type O, Rh negative, crossmatched with maternal serum, gamma irradiated to prevent graft-versus-host reaction) in 10 mL aliquots to raise hematocrit levels to 40%. If blood has been stored, the additive can be removed by washing. If antigen-compatible allogenic blood is unavailable, then maternal RBCs may be utilized (it does not have to be ABO matched). A Tuohy needle is introduced into the peritoneal cavity of the fetus under ultrasound guidance and an epidural catheter is threaded. Specific indications include – A mother who has a history of previous perinatal loss. – Previous need for neonatal exchange transfusion. – High antibody titer. – MCA Doppler suggests anemia. – Ultrasound evidence of fetal hydrops • Fetal intrauterine intravenous transfusion (IVT) is used to treat hydrops fetalis and may require repeat procedures. Anesthesia for the mother is required (sedation or neuraxial). For the fetus, a needle is inserted under ultrasonographic guidance into an umbilical vein and neuromuscular blockade is administered (vecuronium 0.1 mg/kg). Subsequently, blood that is packed, fresh, Type O, Rh negative, cross-matched with maternal serum, and gamma irradiated to prevent graft-versus-host reaction is injected. Maternal blood may be used if antigen-compatible allogenic blood is unavailable (does not require ABO matching). The amount needed is calculated as follows: fetal weight (g) × 0.14. The mother is subsequently admitted to the hospital for 24 hours of observation with continuous monitoring of the fetus. The procedure can be repeated every 10 days for 3 weeks, depending on the severity of the fetal anemia. Complications include transient fetal bradycardia, cord hematoma, umbilical vein compression, and fetal death. • Management of the sensitized newborn – Mild hemolytic disease (mildly anemic with Hg >14 g/dL and bilirubin <4 mg/dL): Treated with early phototherapy. – Moderate hemolytic disease: Although the newborn has some degree of anemia and is not jaundiced at birth, he or she can rapidly develop hyperbilirubinemia in the first 24 hours. This can lead to kernicterus and permanent neural damage. The neonate can receive an exchange transfusion with type-O Rh-negative blood along with intense phototherapy. – Severe hemolytic disease: These newborns are either stillborn or hydrops fetus at birth – Use of IVIG in doses of 0.5–1 g/kg in single or multiple dose regimens have been able to effectively reduce the need for exchange transfusion in the baby. • Emerging treatment methods: Serial plasmaphereses followed by weekly IV immune globulin to the mother is a recent advance.

REFERENCES

1. Elalfy MS, Elbarbary NS, Abaza HW. Early intravenous immunoglobin (two-dose regimen) in the management of severe Rh hemolytic disease of newborn-a prospective randomized controlled trial. Eur J Pediatr. 2011;170(4):461–467. 2. Liumbruno GM, D’Alessandro A, Rea F, et al. The role of antenatal immunoprophylaxis in the prevention of maternal-foetal anti-Rh (D) alloimmunisation. Blood Transfus. 2010;8(1):8–16.

3. Mari G, Russell L. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. N Engl J Med. 2000;342:9–14.

4. Moise KJ. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol. 2008;112(1):164–176.

5. Ruma MS, Moise KF, Kim E, et al. Combined plasmapheresis and intravenous immune globulin for the treatment of maternal red cell alloimmunization. Am J Obstet Gynecol. 2007;196(2):138.e1–6. See Also (Topic, Algorithm, Electronic Media Element) • Transcranial Doppler • Platelets

CODES ICD9 • 773.0 Hemolytic disease of fetus or newborn due to Rh isoimmunization • 999.70 Rh incompatibility reaction, unspecified ICD10 • P55.0 Rh isoimmunization of newborn • T80.40XA Rh incompat react due to tranfs of bld/bld prod, unsp, init

CLINICAL PEARLS

• Approximately 1% of all pregnant women develop Rh alloimmunization. • Since the introduction of exchange and intrauterine transfusions, perinatal mortality has reduced from 50% to 2–3% or less. • About 10% of the infants who received in utero therapy for hemolytic disease of the newborn later develop neurological developmental impairment and hearing loss because of prolonged exposure to high levels of bilirubin and its toxic effect on the developing eighth cranial nerve. • Interestingly, a fetus that is ABO incompatible is less likely to have HDN, because of the rapid removal of the ABO-incompatible RBCs by the naturally occurring anti-A/B antibodies.

RHEUMATOID ARTHRITIS Tayab R. Andrabi

BASICS DESCRIPTION

Rheumatoid arthritis (RA) is a chronic, systemic autoinflammatory disorder characterized by • Deforming symmetrical polyarthritis of varying distribution and severity • Association with synovitis of joint and tendon sheaths • Articular cartilage loss • Erosion of juxta-articular bone (2).

EPIDEMIOLOGY Prevalence

In the US, ∼70 per 100,000 people are diagnosed yearly. Prevalence

• 2–3 times greater in women than men (4). • Increases with age, approaching 5% in women over age 55 • Patients are most commonly first affected in their third to sixth decade of life (4). • Approximately 1–2% worldwide distribution

Morbidity

Relative to the general population, patients with RA are at a • 1.3–1.7 fold higher risk of heart failure (5,6) • 1.5–2 fold higher risk of myocardial infarction (MI) • 1.4–2.7 fold higher risk of stroke Mortality

The life span is thought to be shortened by ∼10 years (1–7), and standardized mortality ratios for RA range from 1.28 to 3.0 (5). ETIOLOGY/RISK FACTORS

• The initiating cause of RA remains unknown, but several factors may contribute. • Approximately 70% of cases are associated with the HLA-DR4 subtype, and 80% of patients are seropositive for rheumatoid factor. • Environmental factors also seem to play a role, including as yet unidentified viral or bacterial agents. • Other risk factors associated with the development of RA include female gender, a family history of RA, food allergies and intolerances, altered gut flora, psychological stress, exposure to heavy metals, and smoking (4).

PHYSIOLOGY/PATHOPHYSIOLOGY

There are two popular theories regarding the pathogenesis of RA. The first holds that the T cell, through interaction with an as yet unidentified antigen, is primarily responsible for initiating the disease and driving the chronic inflammatory process. The second theory holds that while T cells may be important in initiating the disease, chronic inflammation is selfperpetuated by macrophages and fibroblasts in a T-cell independent manner. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Careful assessment for atlantoaxial subluxation (present in up to 25% of patients) and concomitant organ dysfunction. The anesthetic plan should be tailored to specific manifestations (e.g., renal, cardiac, pulmonary disease, etc). • Stress dose steroids should be considered for patients on chronic therapy.

PREOPERATIVE ASSESSMENT SYMPTOMS

Morning stiffness, pain, fatigue, malaise, and depression History

Insidious onset

Signs/Physical Exam

• Symmetric joint swelling • Careful palpation of affected joints can help to distinguish between swelling from inflammation versus bony enlargement from osteoarthritis. • Ulnar deviation of the fingers at the MCP joints, hyperextension or hyperflexion of the MCP and PIP joints, flexion contractures of the elbows, and subluxation of the carpal bones and toes (“cocked-up”).

TREATMENT HISTORY

Total joint arthroplasties can reduce pain and improve function. Other operations include the release of nerve entrapments (e.g., carpal tunnel syndrome), arthroscopic procedures, and occasional removal of a symptomatic rheumatoid nodule. MEDICATIONS

• NSAIDs • Corticosteroids • Disease modifying anti-rheumatic drugs (DMARDs): Methotrexate, sulfasalazine, leflunomide (Arava®), etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), abatacept (Orencia®), rituximab (Rituxan®), anakinra (Kineret®), antimalarials, gold salts, Dpenicillamine, cyclosporin A, cyclophosphamide, and azathioprine (Imuran) (2).

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Cervical spine x-ray: Some authorities recommend that all RA patients should undergo preoperative screening or recent assessment of the cervical spine. • Cervical MRI scan is indicated when neurological signs are present, there is severe pain, or significant abnormality is noted on the plain x-ray film. • ENT consult: A fiberoptic nasopharyngoscopy is indicated for patients with hoarseness because of the likelihood of cricoarytenoid involvement. CONCOMITANT ORGAN DYSFUNCTION

• Neurological. Peripheral neuropathy in the lower extremities is often present with mild, primarily sensory, dysfunction. Entrapment neuropathy, such as carpal tunnel or tarsal tunnel syndromes, may also be seen. Acute subluxation of the cervical spine is a particularly worrisome complication that can cause permanent quadriparesis or death from spinal cord or vertebral artery compression. There are four subtypes: – Anterior comprises 80% of atlantoaxial subluxation. The C1 vertebra moves forward on C2 because of destruction of the transverse ligament and there is a risk of spinal cord compression by the odontoid peg. Subluxation exists when the distance between the atlas and the odontoid peg exceeds 4 mm in patients older than 44 years and 3 mm in younger patients. Anterior atlantoaxial subluxation is worsened by neck flexion. – Posterior comprises 5% of atlantoaxial subluxation. Destruction of the odontoid peg may cause backward movement of C1 on C2, which may be evident on lateral extension views of the neck. Posterior atlantoaxial subluxation is worsened by neck extension. – Vertical comprises 10–20% of atlantoaxial subluxation. Destruction of the lateral mass of C1 can lead to subluxation of the odontoid peg through the foramen magnum and compression of the cervicomedullary junction. – Lateral or rotatory subluxation (rare) results from degenerative changes in the C1/C2 facet joints. It can lead to spinal nerve compression and vertebral artery compression. • Ocular: Keratoconjunctivitis of Sjögren syndrome (most common), episcleritis (mild pain and intense redness), scleritis and corneal ulcerations (rare, but serious) • Sjögren syndrome is a chronic inflammatory disorder characterized by lymphocytic infiltration of lacrimal and salivary glands; seen in 10–15% of patients with RA. This leads to impaired secretion of saliva and tears and results in the sicca complex: Dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca). • Cardiac: Pericardial effusions, pericarditis, cardiac tamponade, myocarditis, amyloidosis, granulomatous disease, endocarditis, left ventricular failure, coronary artery disease (5). • Pulmonary: Restrictive defects from interstitial lung disease (fibrosing alveolitis), rheumatoid nodules, reduced chest wall compliance (costochondral disease) • Vascular: Rheumatoid vasculitis (small digital infarcts along the nailbeds). The abrupt onset of an ischemic mononeuropathy (mononeuritis multiplex) or progressive scleritis is typical Raynaud’s phenomenon. • Renal: Chronic renal failure from drug treatment is seen in ∼25% of patients. • Subcutaneous nodules are the most characteristic extraarticular lesion of the disease; occurs in 20–30% of cases. They are located most commonly on the extensor surfaces of the arms and elbows, but are also prone to develop at pressure points on the feet and knees. Rarely, nodules may arise in visceral organs, such as the lungs, the heart, or the sclera of the eye. • Airway

– Involvement of the cricoarytenoid joints may result in dyspnea, stridor, hoarseness, and occasionally severe upper airway obstruction (3). Patients may also present with a mass in the larynx, which can cause significant disfiguration of the surrounding structures (4). – Laryngeal amyloidosis and rheumatoid nodules may also cause obstruction of the larynx. – The temporomandibular joint (TMJ) may be involved causing limitation of mouth opening and render direct laryngoscopy impossible. – Acute subluxation may cause spinal cord and/or vertebral artery compression leading to quadriparesis or sudden death • Felty syndrome is a rare complication and is characterized by splenomegaly and leukopenia (predominantly granulocytopenia). Recurrent bacterial infections and chronic refractory leg ulcers are the major complication.

CIRCUMSTANCES TO DELAY/CONDITIONS

Unstable atlantoaxial subluxation may require stabilization prior to elective surgery.

TREATMENT PREOPERATIVE PREPARATION Premedications

Patients may have held their NSAIDs for surgery and have pain or discomfort. Preoperative opioids may be considered. Special Concerns for Informed Consent

If an awake fiberoptic intubation (FOI) is planned, indications as well as sedation goals should be discussed with the patient and family. INTRAOPERATIVE CARE Choice of Anesthesia

Regional anesthesia in conjunction with, or in lieu of, general anesthesia should be considered whenever acceptable. Regional and local anesthesia have the advantage of avoiding neck and airway manipulation as well as the systemic effects of drugs used for general anesthesia. However, nerve blocks may be technically challenging because of the loss of anatomic landmarks from contractures and flexion abnormalities. Monitors

• Standard ASA monitors • IV access may be difficult due to vasculitis or thin and fragile skin • Invasive monitors may be considered depending on concomitant disease and surgical procedure – Radial arterial lines may be difficult or inaccessible because of flexion deformities of the wrist joint – Central venous catheters in the internal jugular vein may be difficult to insert secondary to limited neck mobility.

Induction/Airway Management

• Laryngeal mask airway (LMA). If the angle between the oral and pharyngeal axes at the back of the tongue is <90°, it may be difficult to insert; a reinforced LMA may be preferable. Intubating LMAs (ILMA) may be used to achieve blind endotracheal intubation with minimal cervical spine movement. However, the great amount of force that may be exerted on the posterior wall of the pharynx at C2–C3 make the ILMA less attractive as a primary method of intubation. • Endotracheal tube. If the patient does not have signs or symptoms of atlantoaxial subluxation, TMJ disease, or a reduction in neck movement, direct laryngoscopy may be acceptable. However, if suspected, consider alternate strategies – Indirect video laryngoscopy – FOI: If the patient appears easy to ventilate, an asleep FOI may be considered. However, if there are concerns, an awake FOI should be performed. – Surgical tracheostomy can be performed under local anesthesia in patients with cricoarytenoid involvement (2).

Maintenance

• Maintenance with volatile, IV, or a balanced technique are appropriate. • Positioning: Meticulous attention should be paid to padding pressure points and maintaining neutral joint positions. • Methylcellulose eye drops may be appropriate since up to 15% of patients with RA suffer from keratoconjunctivitis. • Stress dose steroids should be administered in patients who are taking on a dose >10 mg daily • Ventilator settings may need to be adjusted in patients with restrictive lung disease.

Extubation/Emergence

Involvement of the cricoarytenoid joints may result in dyspnea, stridor, hoarseness, and occasionally severe upper airway obstruction.

FOLLOW-UP BED ACUITY

Depends on the surgical procedure, concomitant organ disease, or intraoperative events MEDICATIONS/LAB STUDIES/CONSULTS

• Restart anti-inflammatory medications as soon as possible • Continue steroid dosing

REFERENCES

1. Fombon FN, Thompson JB. Anaesthesia for the adult patient with rheumatoid arthritis. BJA. 2006;6(6):235–239. 2. Furst DE, Breedveld FC, Kalden JR. Updated consensus statement on biological agents for

the treatment of rheumatoid arthritis and other immune mediated inflammatory diseases. Ann Rheum Dis. 2003;62:ii2–9. 3. Wolfe F, Freundlich B, Straus WL. Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis. J Rheumatol. 2003;30(1):36–40.

ADDITIONAL READING • Difficult airway • Raynaud’s disease

CODES ICD9

714.0 Rheumatoid arthritis ICD10 • M06.9 Rheumatoid arthritis, unspecified • M06.30 Rheumatoid nodule, unspecified site

CLINICAL PEARLS

• Airway and neck assessment is crucial; atlantoaxial subluxation may be present and there is a potential risk of spinal cord damage. • Regional anaesthesia should be considered as an alternative to general anesthesia.

RIGHT BUNDLE BRANCH BLOCK (RBBB) Tyken C. Hsieh, MD Aman Mahajan, MD, PhD

BASICS DESCRIPTION

Impairment of conduction in the right bundle branch, which comprises one-half of the conduction system within the ventricles. EPIDEMIOLOGY Prevalence

• Increases with age: <1% at age 50 years; 17% by age 80 years. • Most common in elderly men

Morbidity

Generally asymptomatic Mortality

Unlike isolated left bundle branch block (LBBB), isolated right bundle branch block (RBBB) has an excellent prognosis. However, in the presence of known or suspected coronary artery disease (CAD), particularly acute myocardial infarction, RBBB is an independent predictor of increased cardiovascular complications and mortality. ETIOLOGY/RISK FACTORS

• Etiology – Structural heart disease (chronic pulmonary hypertension causing right ventricular hypertrophy; acute pulmonary hypertension as in pulmonary embolism; myocardial ischemia/infarction; idiopathic) – Functional: A transient “rate-related bundle-branch block” may occur with tachycardia where subsequent electrical impulses arrive before full repolarization, producing a functional delay in conduction. – Iatrogenic: Secondary to right heart instrumentation, such as central venous or pulmonary artery catheter placement. It is also a common (50%) complication of alcohol septal ablation for hypertrophic obstructive cardiomyopathy. – Pseudo-RBBB pattern: Brugada syndrome. – Normal variant • Risk factors – Advanced age. RBBB is usually a marker of a progressive degenerative disease that also affects the myocardium. PHYSIOLOGY/PATHOPHYSIOLOGY

• The right bundle branch is one of the two subdivisions of the cardiac conduction system below the bundle of His. It is a long, filamentous structure of rapidly conducting Purkinje cells that courses within the interventricular septum. At approximately the level of the right anterior papillary muscle, it branches into fascicles that spread out to supply the right ventricle (RV). • Normal impulse conduction along the left and right bundle branches results in rapid, coordinated, and synchronized depolarization of the left ventricle (LV) and RV. Impairment of conduction through the right bundle is termed RBBB. • In RBBB, impulses travel normally down the left bundle branch to depolarize the septum and LV, so the initial portion of the QRS complex is normal (septal Q wave followed by an initial R-wave). However, RV depolarization through conduction tissue is blocked and depends on propagation between LV myocytes, and is therefore both slowed and delayed. This delayed LV-to-RV depolarization results in a secondary positive deflection (a secondary R-wave, denoted R’ or r’) in the right precordial leads V1 and V2, and a negative deflection (deep, broad, “slurred” terminal S-wave) in the lateral leads I and V6. The QRS complex is always widened at >120 ms (normal <100 ms).

ANESTHETIC GOALS/GUIDING PRINCIPLES

Isolated RBBB does not require changes to anesthetic management. However, an attempt should be made to rule out possible causes or comorbidities that would change management, including CAD, pulmonary hypertension, or arrhythmias.

PREOPERATIVE ASSESSMENT SYMPTOMS

Inquire about history of palpitations, arrhythmias, syncope, angina, shortness of breath, and exercise intolerance. History

• Associated with advanced age. • May also be associated with CAD or acute or chronic pulmonary hypertension.

Signs/Physical Exam

While there may be physical exam findings with comorbidities, RBBB is a strictly electrocardiographic diagnosis. TREATMENT HISTORY

There is no specific treatment for RBBB MEDICATIONS

Class I or III antiarrhythmic medications may slow conduction through the bundle branches. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

ECG criteria for RBBB

• Complete RBBB – QRS duration greater than or equal to 120 ms in adults; AND, – An rsr′, rsR′, or rSR′ pattern (colloquially referred to as “rabbit ears” or “M”-shaped morphology) in leads V1 or V2. The R′ or r′ deflection is usually wider than the initial Rwave. In a minority of patients, a wide and often notched R-wave pattern may be seen in lead V1 and/or V2. When a pure dominant R-wave with or without a notch is present in V1, the R duration is >50 ms; AND, – S-wave of greater duration than R-wave or >40 ms in leads I and V6 in adults • Incomplete RBBB – Same criteria as for complete RBBB, except QRS duration is between 110 and 120 ms in adults • Baseline ECG in patients with RBBB should be performed to rule out high-grade conduction blocks, arrhythmias, myocardial ischemia/infarction, or evidence of RV hypertrophy. CONCOMITANT ORGAN DYSFUNCTION

If RBBB occurs in the context of pulmonary hypertension, there may be associated RV hypertrophy, dilation, or dysfunction. LV or RV function may be impaired in the setting of myocardial ischemia. CIRCUMSTANCES TO DELAY/CONDITIONS

Acute myocardial ischemia, recent myocardial infarction, or a new high-grade atrioventricular conduction block. CLASSIFICATIONS

Ischemia in the setting of RBBB. The activation of the LV is unaffected, allowing for ischemia patterns (ST elevation and depression) to be recognized. Whereas in LBBB, abnormal repolarization of the LV affects interpretation of the ST segments (and thus diagnosis of ischemia).

TREATMENT PREOPERATIVE PREPARATION

In patients with preexisting LBBB, passage of a pulmonary artery catheter may precipitate temporary RBBB as the catheter contacts the interventricular septum, leading to complete (third-degree) heart block and asystole. Thus, an alternative mechanism to pace the heart must be immediately available. This could include an internal temporary endocardial pacing wire, transcutaneous pacing pads, or epicardial pacing wires. Premedications

Isolated RBBB does not require specific premedication. INTRAOPERATIVE CARE Choice of Anesthesia

Isolated RBBB does not affect the choice of anesthetic technique, monitors, induction/airway

management, maintenance, or extubation and emergence. Monitors

• Standard ASA monitors • Additional hemodynamic monitors (e.g., arterial line), as dictated by comorbidities.

Induction/Airway Management

RBBB does not affect induction or airway management in the absence of significant cardiac comorbidities. Maintenance

Volatile or IV anesthetics are all acceptable. Extubation/Emergence

RBBB does not affect plans for extubation or emergence.

FOLLOW-UP BED ACUITY

Postoperative monitoring according to comorbidities and surgical acuity. MEDICATIONS/LAB STUDIES/CONSULTS

A postoperative 12-lead ECG may be indicated if there is concern for development of new arrhythmia or conduction disturbance. COMPLICATIONS

A RBBB may be induced during central venous catheter placement, pulmonary artery catheter placement, or alcohol septal ablation procedure.

REFERENCES

1. Dorman T, Breslow MJ, Pronovost PJ, et al. Bundle-branch block as a risk factor in noncardiac surgery. Arch Intern Med. 2000;160:1149–1152. 2. Ginsburg G, Neelakantan S, Harrell PG. Acute right bundle branch block as a presenting sign of acute pulmonary embolism. Anesth Analg. 2006;103(3):789–791. 3. Horton CL, Brady WJ. Right bundle-branch block in acute coronary syndrome: Diagnostic and therapeutic implications for the emergency physician. Am J Emer Med. 2009;27:1130– 1141. http://emedicine.medscape.com/article/894927-overview Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram. Part III: Intraventricular conduction disturbances. JACC. 2009;53(11):976–981. See Also (Topic, Algorithm, Electronic Media Element)

• Left bundle branch block • Coronary artery disease

FIGURE 1. Right Bundle Branch Block. Lead V1 demonstrates a secondary positive deflection, or secondary R wave (R’ or

r’). Lateral leads such as V6 demonstrate a negative S-wave that is deep and broad, and described as “slurred.” The QRS complex is widened >120 ms and reflects delayed LV-to-RV depolarization.

CODES ICD9 426.4 ICD10 I45.10 Unspecified right bundle-branch block

CLINICAL PEARLS

• RBBB is common in advanced age. • Isolated RBBB is generally asymptomatic, and does not in itself require changes to anesthetic management. • In patients with RBBB, one should rule out associated CAD, pulmonary hypertension, or high-grade atrioventricular conduction block. • RBBB can be precipitated by pulmonary artery catheter placement in the setting of preexisting LBBB, and alternative pacing capability should be immediately available during this procedure.

ROTATOR CUFF SURGERY Jane C. Ahn, MD Sharon L. Lin, MD

BASICS DESCRIPTION General

• The rotator cuff comprises a group of 4 muscles and their tendons that attach to the humeral head. – Functions to stabilize the glenohumeral joint as well as arm rotation and elevation. – “SITS” muscles: Supraspinatus, Infraspinatus, Teres minor, Subscapularis. • Rotator cuff disease can range from impingement syndrome to full-thickness tears. Tears commonly result from degeneration with resultant chronic tendonitis. Patients presenting for surgery are usually refractory to conservative therapy (leads to improvement in 40–80% of patients (1)) or have an acute, massive injury. • Procedures involve debridement, repair of partial and full-thickness tears, use of muscle flaps and tendon transfers for massive cuff tears, and prosthetics. They can be approached via open, mini-open, or arthroscopic repair. • Open repair – Used primarily for massive tears – More postoperative pain compared to arthroscopic repair – Longer recovery time • Mini-open repair – Most of surgery is performed arthroscopically – Minimizes deltoid injury • Arthroscopic repair – Lower risk of infection and deltoid injury – Mild postoperative pain and stiffness – Risk of respiratory compromise from extravasation of irrigation fluid with prolonged procedures. Position

• Rotator cuff surgery is usually performed in the lateral decubitus or beach chair position depending on surgeon preference. Both have advantages and disadvantages (2). • Lateral decubitus position benefits: – Arm placed in traction allowing better visualization – Decreased risk of hypotension and bradycardia – Cerebral perfusion pressure is well maintained • Lateral decubitus position disadvantages – Traction on operative extremity increases the risk for brachial plexus injury – Must reposition and redrape to convert to open procedure

– Regional blocks as a sole technique are not well tolerated in prolonged procedures and obese patients • Beach chair position benefits – Upright, anatomic position – Ease of exam and mobility of the arm under anesthesia – No need to reposition or redrape if arthroscopic case is converted to open – Regional anesthesia as the sole technique is well tolerated • Beach chair position disadvantages – Increased risk of profound hypotensive and bradycardic events – Increased risk of cerebral and spinal cord ischemia and transient vision loss related to hypotensive events – Increased risk of air embolus

Incision

Incision size depends on surgical technique: (3) • Arthroscopic: 4–7 mm • Mini Open: 3–4 cm • Open: 4–6 cm Approximate Time

Depends on procedure and approach EBL Expected

Depends on extent of procedure and approach. Arthroscopic debridement can be minimal, whereas open procedures, muscle flaps, and prosthetics can be more extensive. Hospital Stay

• Arthroscopic procedures can be performed as an outpatient. • More extensive or complicated repairs may require an inpatient stay for post-operative pain control.

Special Equipment for Surgery

• Arthroscopic equipment if mini-open or arthroscopic techniques planned. • Appropriate tables for positioning (beach chair versus lateral decubitus).

EPIDEMIOLOGY Prevalence

Approximately 150,000 rotator cuff repairs are performed in the US annually (4).

Prevalence

• Increases with age, suggesting that rotator cuff tears develop over time. • Affects 7–30% of adults at any given time (5). Morbidity

• Positioning complications

• Air embolism may also occur from irrigation fluid bags that are under pressure

Mortality

Air embolism, rare

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Deliberate or controlled hypotension may reduce blood loss, which can also improve surgical visualization and prosthetic binding. However, it must be weighed against the potential for end-organ ischemia, particularly in the beach chair position (cerebral perfusion). • Hypotension in the beach chair position should be aggressively treated to avoid cerebral and spinal cord ischemia. • Brachial plexus blocks as a sole anesthetic may be considered; sedation should be titrated appropriately to avoid airway compromise. • Positioning considerations should be made

PREOPERATIVE ASSESSMENT SYMPTOMS

Symptoms depend on degree of rotator cuff injury and can vary. Some patients are asymptomatic. • Pain • Weakness • Range of motion limitation • Limitation of ADLs (activities of daily living) • Atrophy of shoulder musculature

History

• Baseline neurological deficits should be assessed for and clearly documented when performing a brachial plexus block. • Patients may report progressive worsening of pain, weakness, and range of motion in the affected shoulder. • Acute rotator cuff tears may have a history of recent trauma.

Signs/Physical Exam

Functional deficits depend on location of tear MEDICATIONS

Pain medications: NSAIDS, opioids, and muscle relaxants DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

Imaging related to the surgery includes MRIs and ultrasounds. CONCOMITANT ORGAN DYSFUNCTION

Degenerative joint disease

TREATMENT PREOPERATIVE PREPARATION Premedications

Anxiolytics and opioids as needed for brachial plexus block, or prior to general anesthetic induction. Special Concerns for Informed Consent

If a brachial plexus block or catheter is planned as the primary anesthetic or for postoperative pain control, review risks and benefits of regional anesthesia and sedation goals. Antibiotics/Common Organisms

Prophylaxis with a third-generation cephalosporin against Staphylococcal skin flora. INTRAOPERATIVE CARE Choice of Anesthesia

• The anesthetic approach must consider the patient’s and surgeon’s preference as well as the anesthesia provider’s comfort with the procedure. • Brachial plexus block as the sole technique (interscalene or supraclavicular block). – Potential benefit of reduced hemodynamic instability, postoperative delirium, recovery room stay, and systemic opioid administration; as well as avoidance of airway instrumentation and mechanical ventilation. – Potential drawbacks include failed blocks, local anesthetic systemic toxicity, or injury from placement (hemorrhage, nerve damage). – Appropriate for the beach chair position. Poorly tolerated in the lateral decubitus position, particularly in obese patients where airway management and access are concerns. – Placement should allow enough time for onset. – Equipment to convert to a general anesthesia (GA) should be available in the event of a failed or partial block, oversedation, agitation, or anxiety. • General – Can be used in both beach chair and lateral decubitus positions. • Combination of regional and GA – Can be used in both the beach chair and lateral decubitus positions. – Peripheral nerve block/catheter reduces postoperative pain while GA with ETT guarantees secured airway. Monitors

• Standard ASA monitors • End-tidal carbon dioxide monitoring can help detect oversedation with brachial plexus blocks. Induction/Airway Management

Airway management may be with a nasal cannula, LMA, or ETT. Maintenance

• GA: Balanced anesthetic with volatile or IV drugs. Opioid titration when no brachial plexus block. • Brachial plexus block: Light sedation with propofol, dexmedetomidine, or midazolam. • Venous air embolism. Arthroscopic pumps deliver pressures >30 mm Hg that allow air bubbles to enter the joint. This, combined with venous sinusoid exposure in the beach chair position can result in venous air entrainment. Case reports have also cited unintentional air insufflation as well as unrecognized air reservoirs in the 3 L arthroscopic fluid bags as causes. • Arrhythmias from local anesthetics containing epinephrine have been reported (7).

Extubation/Emergence

• GA: Standard extubation criteria • Brachial plexus block: Reorient patient

FOLLOW-UP BED ACUITY

• Routine arthroscopic procedures are typically done as an outpatient. • Extensive, open procedures may require a regular hospital bed for inpatient stay.

ANALGESIA

• IV and oral medications • Single-shot interscalene block with long-acting local anesthetic (bupivacaine or ropivacaine). Insertion of a catheter allows for continuous infusion of local anesthetic.

COMPLICATIONS

• Profound hypotension and bradycardia can occur in 20% of patients undergoing shoulder arthroscopy in the beach chair position (2). This can result in cerebral ischemia, spinal cord ischemia, and visual loss (2). • Air embolism in the beach chair position; also from pressurized irrigating fluid bags. • Airway compromise from extravasated irrigation fluid with prolonged arthroscopic procedures (6,8). • Deltoid dysfunction and postoperative pain (especially with open procedures). • Neurapraxia from brachial plexus traction in the lateral decubitus position. • Brachial plexus block complications; local anesthetic systemic toxicity or needle injury (bleeding, nerve injury).

REFERENCES

1. eruto CM, Ciccotti MG, Cohen SB. Shoulder arthroscopy positioning: Lateral decubitus versus beach chair. Arthroscopy. 2009;25(8):891–896. 2. Ghodadra NS, Provencher MT, Verma NN, et al. Open, mini-open, and all-arthroscopic

rotator cuff repair surgery: Indications and implications for rehabilitation. J Orthop Sports Phys Ther. 2009;39(2):81–89. 3. Freely BT, Gallo RA, Craig EV. Cuff tear arthropathy: Current trends in diagnosis and surgical management. J Shoulder Elbow Surg. 2009;18:484–494.

4. Bedl A, Dines J, Warren RF, et al. Massive tears of the rotator cuff. J Bone Joint Surg Am. 2010;92:1894–1908. 5. Antonucci S, Orlandi P, Mattei PA, et al. Airway obstruction during arthroscopic shoulder surgery: Anesthesia for the patient or for the surgeon? Minerva Anestesiol. 2006;72:995– 1000. 6. Venkat G, Moon YL, Na WC, et al. Upper airway compromise by extravasated fluid: A rare complication after arthroscopic repair of atrophic cuff tear. Orthopedics. 2009;32(10). doi: 10.3928/01477447-20090818-32. 7. Zmistowski B, Austin L, Ciccotti M, et al. Fatal venous air embolism during shoulder arthroscopy. J Bone Joint Surg Am. 2010;92:2125–2127. 8. Cho SH, Yi JW, Kwack YH, et al. Ventricular tachycardia during arthroscopic shoulder surgery: A report of two cases. Arch Orthop Trauma Surg. 2010;130(3):353–356. See Also (Topic, Algorithm, Electronic Media Element) • Controlled hypotension • Venous air embolism

CODES ICD9 • 726.2 Other affections of shoulder region, not elsewhere classified • 726.13 Partial tear of rotator cuff • 727.61 Complete rupture of rotator cuff ICD10 • M75.100 Unsp rotatr-cuff tear/ruptr of unsp shoulder, not trauma • M75.110 Incmpl rotatr-cuff tear/ruptr of unsp shoulder, not trauma • M75.120 Complete rotatr-cuff tear/ruptr of unsp shoulder, not trauma

CLINICAL PEARLS

• Place the noninvasive BP cuff on the nonoperative arm rather than the calf to obtain more accurate BP measurements for patients in the beach chair position. • Obese patients are at greater risk of hypotension in the beach chair position because compression of the vena cava decreases venous return. • Hyperextension and rotation of the head can decrease vertebral artery blood flow causing infarcts of the posterior cerebral circulation. • Monitor for fluid extravasation and airway edema with excessive irrigation in prolonged arthroscopy procedures.

• Consider regional, general, or combined regional and general techniques on a case by case basis. • A brachial plexus block will block the diaphragm (C3, C4, C5) and may cause respiratory embarrassment in patients with underlying pulmonary disease. Conversely, the administration of opioids for analgesia has drawbacks.

SACROILIAC (SI) JOINT INJECTIONS Zachary M. Zumbar, MD, MPH Beth H. Minzter, MD, MS, FIPP

BASICS DESCRIPTION

• Pain from the sacroiliac (SI) joint accounts for 10–30% of cases of low back pain. • SI pain is more common in women. During pregnancy, the incidence may be as high as 80%. • The symptoms of SI joint pain can be difficult to distinguish from other pain syndromes such as lumbar facet arthropathy, lumbar radiculopathy, hip arthropathy, and myofascial pain. PHYSIOLOGY PRINCIPLES

• Functions of the SI joint include shock absorption during weight bearing and storage of elastic energy via force transfer into the sacrum. • The mobility of the joint is limited, but it is capable of small amounts of rotation and translation. ANATOMY

• The SI joint is the largest axial joint in the body. It is a diarthrodial joint, meaning that it has a joint capsule, synovial fluid and lining, and cartilaginous surfaces that allow movement. • Anterior capsule: Only portion that is truly synovial. It is innervated by the ventral rami of L4 through S2 with possible contributions from L2 and L3. • Posterior capsule: Poorly developed posterior ligamentous structure that serves to limit motion. It is innervated by the dorsal rami of L5 through S3 with possible contributions from L3, L4, and S4. PHYSIOLOGY/PATHOPHYSIOLOGY

• Causes of SI joint pain: – Axial loading; forces are transmitted along the axis of the spine – Extraneous compression or transference of shearing forces, for example, from the lower extremities or pelvis – Abrupt rotation – Abnormal mechanics, such as hypomobility or hypermobility of the joint complex – Disruption or tension of the joint capsule, synovium, or ligaments – Fracture – Chondromalacia – Inflammation from infection, malignancy, or spondyloarthropathy – Malignancy • Predisposing factors – Leg length discrepancy

– Gait abnormality – Strenuous exercise – Scoliosis – Lumbosacral spinal fusion or other lumbar spine surgery – Infection – Trauma – Spondyloarthropathy – Pregnancy • Findings on history – Pain in the superomedial and possibly superolateral buttock inferior to the posterior superior iliac spine (PSIS) – Absence of pain above L5 – Referred pain to the lateral thigh and groin, or less commonly to the posterior thigh or leg – Aggravation with bending, sitting, or rising – Relief with standing or walking • Physical exam findings. Each of the tests described below are considered positive if they produce pain localized to the SI joint and/or reproduce the patient’s pain. – Tenderness to palpation at the posterior aspect of the joint – Provocative tests such as the Patrick test: With a supine patient, flex the ipsilateral knee and place the foot on the contralateral patella or thigh. Stabilize the contralateral hip and lower the knee toward the examining table. Gaenslen test: Place the patient supine, while allowing one leg to hang over the table. Have the patient pull the knee on the table up to the chest. Apply pressure to the leg hanging off the table. Yeoman test: Place the patient prone and extend the leg at the hip while rotating the ilium. Thigh thrust: With the patient supine, the hip is flexed to 90° with the knee flexed. The examiner places a hand on the sacrum for stabilization and applies a posterior shearing stress to the SI joint through the femur. Posterior shear: With the patient in the prone position, the palm of the examiner’s hand is placed over the posterior iliac wing. An inferiorly directed thrust produces a shearing force across the SI joint. Distraction: With the patient supine, a posterolateral force is applied to both the anterior and superior iliac spines to stretch the anterior SI ligaments and synovium. Compression: With the patient in a lateral position, downward pressure is applied to the uppermost iliac crest, directed toward the opposite iliac crest. This is intended to stretch the posterior SI ligaments and compress the anterior SI joint. Gillet test: With the patient upright (standing), the examiner’s left thumb is placed over the posterior-most portion of the left PSIS and the right thumb overlies the midline of the sacrum at the same level. The patient maximally flexes the left hip and knee with a minimum of 90° of hip flexion. The thumb placements are reversed to test the right side. A negative test finds the thumb on the PSIS moving caudally in relation to the thumb on the sacrum. A positive finding occurs when the thumb on the PSIS does not move at all

or moves cranially in relation to the thumb placed on the sacrum. This test assesses movement of the innominate bone posteriorly on the sacrum, thus if it does not move caudally, the joint is not moving correctly in posterior tilt. • Diagnosis – Pain relief from an intraarticular injection is the gold standard. – Individual factors in the history and physical exam have low sensitivity, low specificity, or both. – Radiologic imaging has a low sensitivity and is not useful as a screening test. • Management – Conservative therapies Bracing Manual manipulation Physical therapy NSAIDs and amitriptyline may be used for pain control – Disease-modifying antirheumatic drugs (DMARDs), steroids, or biologic agents may be used to treat spondyloarthropathies and improve pain. – Invasive therapies include intraarticular and periarticular joint injections, radiofrequency ablation (RFA), and some alternative therapies – Intraarticular injections with local anesthetic and steroid can be both diagnostic and therapeutic. Most studies have shown benefit from intraarticular steroid injections from 1 to 12 months. The most common method of performing an intraarticular SI injection is with fluoroscopic guidance. Sterile technique must be maintained. An AP view of the joint is obtained with the patient prone. The C-arm is rotated obliquely until a clear view of the joint is obtained in which the anterior and posterior portions of the joint overlap. Using a 22- to 25-gauge needle, the posterior joint is entered close to the most inferior aspect. After negative aspiration, contrast is injected to confirm intraarticular spread, and a mixture of local anesthetic and steroid is injected into the joint. – Periarticular steroid injections have also been shown to provide good short-term relief. These are performed in a manner similar to intraarticular injections, with the exception that the steroid is deposited around the joint as opposed to inside it. – RFA of the dorsal rami supplying the posterior joint may provide longer-lasting relief in patients who respond well to intraarticular blocks. The joint itself can also be targeted for RFA, but RFA of the nerves is more effective. There is debate as to how many intraarticular injections should be done before proceeding to RFA. – Other treatments that have been used but are less well studied include surgical stabilization, hyaluronic acid injections, botox injections, prolotherapy, and neuroaugmentation.

GRAPHS/FIGURES

FIGURE 1. Anterior view of the anatomy of the sacroiliac joint.

FIGURE 2. Intraarticular sacroiliac injection. The sacroiliac joint is approached posteriorly.

REFERENCE

1. Benzon HT, Rathmell JP, Wu CL, et al. (eds). Raj’s Practical Management of Pain, 4th ed. Philadelphia: Mosby/Elsevier, 2008. 2. Cohen SP. Sacroiliac joint pain: A comprehensive review of anatomy, diagnosis, and treatment. Anesth Analg. 2005;101:1440–1453. 3. Dreyfuss P, Henning T, Malladi N, et al. The ability of multi-site, multi-depth sacral lateral branch blocks to anesthetize the sacroiliac joint complex. Pain Medicine. 2009;10:679– 688. 4. Dreyfuss P, Michaelsen M, Pauza K, et al. The value of medical history and physical examination in diagnosing sacroiliac joint pain. Spine. 1996;21:2594–2602.

5. Ostgaard HC, Andersson GJ, Karlsson K. Prevalence of back pain in pregnancy. Spine. 1991;16:549–552. 6. Raj PP, Lou L, Erdine S, et al. (eds). Interventional Pain Management: Image-Guided Procedures, 2nd ed. Philadelphia: Saunders Elsevier, 2008.

7. Rathmell JP. Atlas of Image-Guided Intervention in Regional Anesthesia and Pain Medicine and Complications in Regional Anesthesia and Pain Medicine. Philadelphia: Lippincott Williams & Wilkins, 2006. See Also (Topic, Algorithm, Electronic Media Element) • Radiation exposure • Facet joint injections

CLINICAL PEARLS

• The SI joints are a common source of low back pain. • Intraarticular blocks are useful for both diagnosis and treatment of SI joint pain. • Both conservative and invasive therapies are available. • Spillover of local anesthetic onto the sciatic nerve may produce short-term lower extremity weakness after both intraarticular and periarticular injections.

SARCOIDOSIS

Linh Trang Nguyen, MD

BASICS DESCRIPTION

• Sarcoidosis is a multisystem inflammatory disease characterized by noncaseating epithelioid granulomas. • Virtually every organ may be involved with the lung being most frequently affected (>90% of patients). Other common areas include the skin (30%), eyes (25%), and lymph nodes (1). 5% of patients have diagnosed cardiac involvement, although autopsies reveal up to 30% subclinical involvement (2). • It is a diagnosis of exclusion. Granulomas must be present in at least 2 organs. Lymphoma as well as mycobacterial and fungal infections need to be considered in the differential diagnosis of sarcoidosis when the CXR shows bilateral hilar adenopathy. A tissue diagnosis is usually required, and other causes of multisystem granulomatous diseases must be excluded (3).

EPIDEMIOLOGY Prevalence

• In the US: 10.9 cases per 100,000 among the white population (1) • 35.5 cases per 100,000 among the black population (1)

Prevalence

• Most patients are between 20 and 40 years old, although it can be seen in children and the elderly (a second peak occurs in women over 50 years of age) (4,5). • In Europe, the majority of sarcoidosis patients are white or Nordic (4). • More prevalent among nonsmokers

Morbidity

• May be asymptomatic • Chronic in one-third of patients (1) • Two-thirds of patients experience spontaneous remission within 10 years of diagnosis. However, 10–30% of patients have a more chronic or progressive course (1). • In blacks, the disease presentation is usually more severe and chronic. Additionally, more extensive and chronic pulmonary disease is seen (1,6). Mortality

Ranges from 1% to 5% (6). Often due to severe involvement of lung parenchyma, leading to pulmonary fibrosis and respiratory failure; myocardial involvement, leading to lethal arrhythmias (VT) and congestive heart failure; and neurological involvement (2) ETIOLOGY/RISK FACTORS

Unknown etiology (3). The hypothesis is that sarcoidosis is due to environmental exposure to an infectious (herpes virus, mycobacterium, propionibacterium) or noninfectious agent (beryllium, mold, mildew, pesticides) which triggers an inflammatory response in a genetically predisposed host (HLA-A1, B8, DR-3) (1,2,3,7) PHYSIOLOGY/PATHOPHYSIOLOGY

• Noncaseating granulomas, which consist of macrophages, CD4 type I helper T cells, CD8 Tlymphocytes, and B-lymphocytes, form in many organs and disrupt the normal architecture of the organ (1,3) • If there is spontaneous resolution of the granulomas, then there are no clinical sequelae. However, at least 20% of patients appear to develop a chronic form of the disease; associated with the secretion of high levels of interleukin 2, interferon gamma and tumor necrosis factor (TNF) (1). These cytokines play an important role in the granulomatous inflammatory process, and are the targets of immunosuppressive drugs used to treat sarcoidosis. • Severe organ impairment occurs if there is scarring or fibrosis from the granuloma resolution.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess the severity of disease and identify the organ systems involved • Medications. History and side effects, especially for immunosuppressive and antimalarial drugs, should be elicited. Patients on corticosteroids may require a stress dose.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Can be vague, and mimic those of cancer symptoms, including fatigue, weight loss, body aches, lack of energy, fever • Dry eyes, blurry vision, light sensitivity, eye pain with ophthalmic involvement • Dyspnea, dysphagia with laryngeal involvement (8) • Syncope, heart failure with cardiac involvement • Shortness of breath, dry, nonproductive cough with pulmonary involvement • Arthritis with joint involvement

History

• Disease onset, length of time since diagnosis • Cardiopulmonary functional status

Signs/Physical Exam

• Eye redness from uveitis • Dysphonia, stridor with laryngeal involvement (8) • Arrhythmia, jugular venous distension, hepatomegaly, lower extremity edema from congestive heart failure • Hypoxemia from pulmonary sarcoidosis, fine crackles, expiratory wheeze may be present on lung exam

• Tender, red skin nodules from erythema nodosum. Subcutaneous tissue surrounding the sarcoid osseous lesions may be inflamed, erythematous, and swollen • Hepatomegaly, jaundice • Joint swelling and erythema

MEDICATIONS

• Not all patients require therapy; spontaneous remission occurs in a large number of patients. • Glucocorticoids are considered first-line therapy (1). The treatment duration ranges from 6 to 9 months (topical, inhaled, oral depending on organ involved); optimal dosing and duration are unknown (7). For pulmonary sarcoidosis, 3–4 weeks are usually needed before major improvements are seen. Side effects include weight gain, osteoporosis, glucose intolerance, delayed wound healing, and infections (6). • Other immunosuppressive drugs, including chloroquine, methotrexate, azathioprine, TNFalpha inhibitors (infliximab, adalimumab) are considered second-line therapy. Side effects include myelosuppression and leucopenia, elevated LFTs, infections, lymphoma, and cardiomyopathy (6). • Cyclophosphamide and thalidomide are used only in unremitting, refractory disease that is unresponsive to first- or second-line therapy. Cyclophosphamide may cause hemorrhagic cystitis, and thalidomide may cause deep vein thromboses (6).

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• BUN, Cr: Assess renal function • Serum calcium: May be elevated from increased intestinal absorption due to overproduction of calcitriol by pulmonary macrophages • CBC: May demonstrate the presence of anemia, thrombocytopenia, eosinophilia • LFTs: May be elevated with liver involvement. If so, may consider testing synthetic function with coagulation tests. • Hemoglobin A1C: May be elevated due to chronic corticosteroid use • Serum ACE levels: Angiotensin converting enzyme is secreted by the epithelioid cells of granulomas, and may reflect the granuloma load. However, ACE levels has not been found to be useful in monitoring disease activity and treatment response (3). • PFT: May reveal reduced lung volumes (decreased FEV1 and FVC), and decrease in the diffusing capacity for carbon monoxide (3) • CXR: May show hilar lymphadenopathy and interstitial infiltrates 95% cases have bilateral lymphadenopathy, 5% cases have unilateral lymphadenopathy (1) • EKG: May demonstrate abnormalities such as atrioventricular (AV) block and ventricular arrhythmias (2) • Echocardiogram study to assess left ventricular function and to look for the presence of pulmonary hypertension • High-resolution CT to look for hilar and mediastinal lymphadenopathy • Ophthalmologic examination looking for signs of uveitis • Muscle enzymes may be elevated with sarcoid myositis (7)

CONCOMITANT ORGAN DYSFUNCTION

Sarcoidal granulomas in the different tissues and organs lead to the following presentations:

• Nervous system: Peripheral neuropathies, meningitis, encephalitis, seizures, diabetes insipidus due to pituitary involvement, cranial nerve palsies, especially CN2 and CN7 paraplegia or quadriplegia with spinal cord involvement (1) • Eyes: Uveitis, blindness in severe cases (8) • Larynx (0.5–8.3%): Vocal cord edema, supraglottic obstruction from granulomas of epiglottis, aryepiglottic folds, and arytenoids (8) • Cardiac: Restrictive cardiomyopathy, conduction abnormalities, and arrhythmias (2) • Lungs: Most commonly affected and includes parenchymal disease, hilar and mediastinal involvement, pulmonary fibrosis, and pulmonary hypertension • Liver: Hepatomegaly • Spleen: Splenomegaly • Kidneys: Glomerulonephritis, interstitial nephritis, nephrocalcinosis, and nephrolithiasis • Skin: Erythema nodosum • Osseous involvement in 13% of patients (7) • Joints: Arthritis • Sarcoid myopathy in 75% of patients. May be asymptomatic (the majority) or may cause myositis leading to muscle contracture and hypertrophy (7).

CIRCUMSTANCES TO DELAY/CONDITIONS

• Lung involvement is common; there is no need to postpone an elective surgery unless there is an active infection, severe wheezing, or recent pulmonary embolism. • Right heart failure and cor pulmonale • High-grade AV block requiring pacemaker implantation • Ventricular arrhythmia requiring implantable cardioverter-defibrillator (ICD) placement • Left ventricular dysfunction requiring optimization with heart failure medications (ACE inhibitors, ARBs, beta-blockers, diuretics) and cardiac resynchronization therapy

CLASSIFICATIONS

• Onset: Acute, subacute, or insidious • Pulmonary sarcoidosis is classified as stage 0–4 depending on the presence of intrathoracic adenopathy, pulmonary infiltrates, and pulmonary fibrosis (3). • Lofgren syndrome is a type of acute sarcoidosis characterized by the triad of erythema nodosum, bilateral hilar adenopathy, and arthritis (1). • Heerfordt’s syndrome is a rare type of sarcoidosis consisting of uveitis, parotid swelling, fever, and facial nerves palsy (3).

TREATMENT PREOPERATIVE PREPARATION Premedications

• Stress-dose steroids should be considered for patients on chronic steroids. • Prophylactic dexamethasone may be considered for patients with laryngeal involvement

requiring airway instrumentation. • Pacemaker and ICDs, if present, should be appropriately interrogated and managed.

Special Concerns for Informed Consent Regional anesthesia, if planned INTRAOPERATIVE CARE Choice of Anesthesia

Depends on surgical procedure and patient preference. Regional anesthesia should be considered when there is severe lung involvement and cor pulmonale. Thrombocytopenia may be present, and may limit the choice of regional technique such as epidurals Monitors

• Standard ASA monitors • Consider arterial line placement in patients with severe lung or cardiac involvement to monitor arterial blood gases and for beat-to-beat blood pressure monitoring

Induction/Airway Management

• Laryngeal involvement may require fiberoptic intubation or the use of a smaller endotracheal tube. • Airway compression may present due to enlarged paratracheal lymph nodes.

Maintenance

• Ventilation: In patients with pulmonary hypertension, hypoxia and hypercarbia increase pulmonary pressures and should be avoided. In patients with pulmonary fibrosis, avoid excessive airway pressures to reduce the incidence of barotrauma. • Medications. Altered drug metabolism and excretion may be present with concomitant kidney and liver disease. • Fluids. Meticulous management in patients with cardiomyopathy. • Attention to pressure points, and adequate padding in patients on chronic steroids and fragile skin

Extubation/Emergence

Full reversal of neuromuscular blockade is warranted before extubation of a patient with limited pulmonary reserve.

FOLLOW-UP BED ACUITY

Depends on the surgical procedure, severity of disease, and perioperative events MEDICATIONS/LAB STUDIES/CONSULTS

• Judicious use of opioids in patients with poor pulmonary function; consider regional anesthesia • Supplemental oxygen should be administered, as appropriate

• Monitor for life-threatening airway obstruction and respiratory arrest in patients with laryngeal involvement • Cardiac monitoring should be considered for patients with conduction abnormalities and arrhythmias.

COMPLICATIONS

• Fluid overload, cardiac arrhythmias, congestive heart failure, and pulmonary edema may occur in patients with cardiac sarcoidosis and cardiomyopathy. • Hypotension from adrenal cortical suppression from chronic corticosteroid use may occur.

REFERENCES

1. Iannuzzi MC, Fontana JR. Sarcoidosis: Clinical presentation, immunopathogenesis, and therapeutics. JAMA. 2011;305(4):391–399. 2. Soejima K, Yada H. The work-up and management of patients with apparent or subclinical cardiac sarcoidosis: With emphasis on the associated heart rhythm abnormalities. J Cardiovasc Electrophysiol. 2009;20(5):578–583. 3. Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183(5):573–581. 4. American Thoracic Society. What is Sarcoidosis? American Journal of Respiratory and Critical Care Medicine. 2006;173:P3–P4. 5. Baughman RP, Teirstein AS, Judson MA, et al. Clinical Characteristics of Patients in a CaseControl Study of Sarcoidosis. American Journal of Respiratory and Critical Care Medicine. 2001;164:1885–1889. 6. Lazar CA, Culver DA. Treatment of sarcoidosis. Semin Respir Crit Care Med.2010;31(4):501–518. 7. Sweiss NJ, Patterson K, Sawaqed R, et al. Rheumatologic manifestations of sarcoidosis. Semin Respir Crit Care Med. 2010;31(4):463–473. 8. Mayerhoff RM, Pitman MJ. Atypical and disparate presentations of laryngeal sarcoidosis. Ann Otol Rhinol Laryngol. 2010;119(10):667–671. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary hypertension • Pacemaker dependent • Pulmonary function tests

CODES ICD9 • 135 Sarcoidosis • 517.8 Lung involvement in other diseases classified elsewhere ICD10

• D86.0 Sarcoidosis of lung • D86.3 Sarcoidosis of skin • D86.9 Sarcoidosis, unspecified

CLINICAL PEARLS

• Sarcoidosis is a systemic disease, with an uncontrolled cellular immune response affecting multiple organs therefore, a complete preoperative assessment is necessary, with particular emphasis on pulmonary and cardiac involvement. Due to the lack of a pathognomonic test for sarcoidosis, and the nonspecific symptomatologies, patients may present to the preoperative clinic without an established diagnosis of sarcoidosis. Instead, they may have been given a diagnosis of asthma or bronchitis. • Immunosuppressive drugs used to treat sarcoidosis may cause significant toxicities and should be carefully reviewed.

SCIATIC NERVE BLOCK Jane C. Ahn, MD Sharon L. Lin, MD

BASICS DESCRIPTION

• The sciatic nerve is the largest peripheral nerve in the human body; it provides motor and sensory innervation. • The sciatic nerve block can be used in combination with a lumbar plexus, femoral, or saphenous block in order to provide anesthesia and analgesia to the entire lower extremity. Additionally, – It may provide site-specific anesthesia and minimize the need for general anesthesia during outpatient surgery, thus minimizing the length of stay and cost (1). – It provides postoperative analgesia, decreasing opioid consumption and side effects (1). – A catheter can be placed to provide continuous infusion of local anesthetic and prolonged analgesia. • Sciatic nerve blocks can be performed utilizing a variety of technologies including peripheral nerve stimulation (PNS) and/or ultrasound guidance (US). PHYSIOLOGY PRINCIPLES

• The sciatic nerve provides sensory innervation to the posterior thigh, knee, part of the knee joint, and the entire leg below the knee except for the medial aspect (this is supplied by the saphenous nerve, a branch of the femoral nerve). • It supplies motor function to hamstrings and flexor and extensor muscles of the ankles and feet. • A distal sciatic nerve block (popliteal block) will spare sensation to the posterior thigh and knee as well as motor function to the hamstrings.

ANATOMY

• The sciatic nerve originates from the lumbosacral plexus, L4-S3 nerve roots. • It exits the greater sciatic foramen and travels caudally along the piriformis muscle posterior to the femur. • It bifurcates into 2 terminal branches ∼7–8 cm proximal to the popliteal crease in the popliteal fossa: Tibial nerve (located medially) and common peroneal nerve (located laterally). • The tibial and common peroneal nerves are enclosed in a common nerve sheath.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Major complications from lower extremity nerve blocks are rare compared to other peripheral nerve blocks (e.g., brachial plexus and eye blocks) • Nerve injury may be due to the following (2):

– Trauma from the needle – Local anesthetic neurotoxicity – Local anesthetic systemic toxicity – Ischemic injury secondary to pressure and volume of the local anesthetic – Addition of vasoconstrictors – Hematoma or vascular injury – Surgical trauma and positioning – Tourniquet injury – Postoperative swelling and positioning – Preexisting pathology • Sciatic nerve injury accounts for 3% of nerve injuries associated with peripheral nerve blocks from ASA Closed Claims Database (3).

PERIOPERATIVE RELEVANCE

• A sciatic nerve block is an alternative to epidural or spinal anesthesia for lower extremity surgery if used in conjunction with a lumbar plexus, femoral, or saphenous nerve block. It can also serve as an alternative to patient refusal or when coagulopathies preclude neuraxial blocks. • The sciatic nerve can be blocked anywhere along its course from the parasacral space to the popliteal fossa: – A proximal sciatic block is recommended in combination with lumbar plexus or femoral block for procedures involving the thigh, knee, or thigh tourniquet. – A distal sciatic block (popliteal block) is recommended in combination with a saphenous block for procedures of the lower leg, ankle, or foot. It has the benefit of allowing the patient to ambulate with crutches because hamstring function is preserved. • Peripheral nerve stimulation versus ultrasound. Data indicates that US guidance for sciatic nerve blocks can improve the onset and success of sensory blockade as well as decrease the local anesthetic requirements and time to perform the block (level IB evidence for Grade A recommendation (4). However, clinical relevance in differences between PNS versus US techniques is ultimately dependent on experience and comfort of the clinician. • The parasacral approach (of Mansour) blocks the entire sacral plexus before it forms the sciatic nerve when it exits the greater sciatic foramen. It is the most proximal approach (5) (Figure 1). – Position: Lateral (Sim’s) position – Landmarks: Posterior superior iliac spine (PSIS) and ischial tuberosity with a line connecting the two points – Needle insertion point: 6 cm inferior to the PSIS along the line – Depth: ∼5–8 cm – Redirection: If bone is contacted, the needle should be redirected 1 cm inferior and advanced no further than an additional 2.5 cm – Other: Performed in close proximity to pelvic vessels and viscera

FIGURE 1. Parasacral approach (of Mansour). a = posterior superior iliac spine, b = ischial tuberosity. The needle insertion point is ∼6 cm inferior to Point a.

• The classic approach (Labat–Winnie) blocks the sciatic nerve after it exits the greater sciatic foramen distal to the piriformis muscle (6). – Position: Lateral (Sim’s) position – Landmarks: Greater trochanter (GT), PSIS, sacral hiatus. One line is drawn connecting the GT and PSIS and a second line is drawn connecting the GT and sacral hiatus. A perpendicular line bisecting the first line and intersecting the second line is drawn – Needle insertion point: The intersection of the perpendicular line with the 2nd line (GT to sacral hiatus). – Depth: ∼6–7 cm – Other: The needle traverses multiple muscle layers and may cause greater discomfort. • The anterior approach blocks the sciatic nerve as it passes posteriorly behind the femur at the level above the lesser trochanter (7) (Figure 2). – Position: Supine – Landmarks: Inguinal ligament (line connecting anterior superior iliac spine and pubic tubercle). A perpendicular line is drawn bisecting the inguinal ligament and extending 8 cm caudad. – Needle insertion point: Needle is inserted perpendicular to the skin, 8 cm distally along the line perpendicular to the midpoint of the line connecting the anterior superior iliac spine and pubic tubercle.

FIGURE 2. Anterior approach to the sacral nerve. The inguinal ligament is identified by drawing a line from the anterior

superior iliac spine to the pubic tubercle. At the midpoint, a perpendicular line is drawn caudally. Needle insertion is 8 cm from this point.

– Depth: ∼10–11 cm – Other: May require multiple needle passes to “walk off” the lesser trochanter. By also blocking the posterior femoral cutaneous nerve, tourniquet pain can be prevented. The femoral nerve may be inadvertently encountered when performing the block; therefore monitor for patellar stimulation. • Subgluteal approach (di Benedetto) blocks the sciatic nerve more distally, caudal to the gluteus muscles (6). It is located in a palpable sulcus between the biceps femoris and semitendinosus muscles (aka “Sciatic Line”) (Figure 3). – Position: Lateral (Sim’s) – Landmarks: GT, ischial tuberosity with a line connecting the two points. A second line is drawn from the midpoint of the first line, perpendicular and extending 4 cm caudally. – Needle insertion point: Needle is inserted perpendicular to the skin, 4 cm caudally in the line perpendicular to the midpoint of the line connecting the GT and ischial tuberosity. A depression should be palpated at this level and represents the groove between the biceps femoris and semitendinosus muscles. – Depth: ∼4–5 cm – Other: There is no difference in block failure rate between the classic and subgluteal approach (5).

FIGURE 3. Subgluteal Approach.

• Posterior popliteal approach blocks the sciatic nerve above the popliteal crease before dividing into the tibial and common peroneal branches (8). – Position: Prone – Landmarks: At the level of popliteal crease, palpate the biceps femoris tendon (laterally) and semimembranosus and semitendinosus tendons (medially). Ask the patient to tense hamstrings to accentuate the tendons. Follow the biceps femoris cephalad until the border of the popliteal apex is reached (the intersection of biceps femoris and semimembranosus and semitendinosus muscles). – Needle insertion point: 0.5 cm below the apex of the fossa – Depth: ∼4–5 cm – Other: A higher rate of success is noted if inversion is elicited with nerve stimulation compared to eversion (8). Tibial nerve stimulation results in plantar flexion of the foot or

toes. The common peroneal nerve stimulation results in dorsiflexion of the foot or extension of the toes (Figure 4).

FIGURE 4. Popliteal approach to the sciatic nerve on ultrasound. BFlh is biceps femoris long head. BFsh is biceps femoris short head.

• The lateral popliteal approach also blocks the sciatic nerve above the popliteal crease before bifurcating, but allows the patient to remain supine that may be helpful in patients who are obese or unable to tolerate prone position due to pain or orthopedic apparatus (9) (Figure 5). – Position: Supine – Landmarks: Groove between the biceps femoris and vastus lateralis muscle on the lateral aspect of the leg. – Needle insertion site: Is in a horizontal plane 11 cm cephalad to the most prominent point of the lateral femoral epicondyle. – Depth: Insert needle until the femur is contacted, then redirect 30° posteriorly until plantar flexion is elicited with nerve stimulation. – Other: See posterior popliteal block approach

FIGURE 5. Lateral Popliteal Approach.

REFERENCE

1. lein SM, Evans H, Neilson KC, et al. Peripheral nerve block techniques for ambulatory surgery. Anesth Analg. 2005;101(6):1663–1676. 2. Liguori GA. Complications of regional anesthesia: Nerve injury and peripheral blockade. J Neurosurg Anesthesiol. 2004;16(1):84–86.

3. Lee LA, Domino KB. Complications associated with peripheral nerve blocks: Lessons from the ASA Closed Claims Project. Int Anesth Clin. 2005;43(3):111–118.

4. Salinas FV. Ultrasound and review of evidence for lower extremity peripheral nerve blocks. Reg Anesh Pain Med. 2010;35:S16–S25. 5. Ripart J, Cuvillon P, Nouvellon E, et al. Parasacral approach to block the sciatic nerve: A 400 case study. Reg Anesth Pain Med. 2005;30:193–197. 6. Di Benedetto P, Bertini L, Casati A, et al. A new posterior approach to the sciatic nerve block: A prospective randomized comparison with the classic posterior approach. Anesth Analg. 2001;93:1040–1044. 7. Chelly JE, Delaunay L. A new anterior approach to the sciatic nerve bock. Anesthesiology. 1999;91(6):1655–1660. 8. Borgeat A, Blumenthal S, Karovic D, et al. Clinical evaluation of a modified posterior anatomical approach to performing the popliteal block. Reg Anesth Pain Med. 2004;29:290–296. 9. Taboada M, Alvarez J, Cortes J. The effects of three different approaches on the onset time of sciatic nerve blocks with 0.75% ropivacaine. Anesth Analg. 2004;98:242–247. See Also (Topic, Algorithm, Electronic Media Element) • Femoral nerve block • Epidural • Local anesthetic systemic toxicity

CLINICAL PEARLS

• There are multiple approaches to blocking the sciatic nerve along its course as it originates from the lumbosacral plexus and travels distally. • Avoid epinephrine for proximal sciatic nerve blocks due to the risk of sciatic nerve ischemia resulting from a combination of vasoconstrictive effects, nerve stretching, and compression from a tourniquet. • Give patients clear instructions regarding fall precautions as they may have hamstring weakness (proximal sciatic nerve block) or foot drop (popliteal block). • The lateral approach to the popliteal block may be well suited for patients who are obese or unable to tolerate the prone position.

SCLERODERMA Andrea Parsons, MD

BASICS DESCRIPTION

• Scleroderma is an inflammatory, connective tissue disease characterized by vascular sclerosis, and fibrosis of the skin and viscera. • Patients with the disease may present for surgical management of pericardial effusions, upper gastrointestinal procedures, dysrhythmias, and renal dysfunction, or for nonrelated problems. EPIDEMIOLOGY Prevalence

• Difficult to determine due to its variable protein manifestations • Diffuse scleroderma: 20 in 1,000,000 people

Prevalence

• Four times more likely to develop in women • Onset most commonly between 30 and 50 years of age • African Americans have an increased prevalence compared to Caucasians as well as greater diffuse skin involvement, incidence of pulmonary fibrosis, and overall worsened prognosis. Morbidity

• Prognosis depends on the extent of visceral involvement rather than cutaneous involvement. • Cardiac, renal, and GI tract involvement can result in a significant decline in quality of life.

Mortality

• Limited disease: May have a normal life expectancy. • Severe diffuse disease is seen in up to 10% of patients and has a 50% survival rate at 5 years. • Leading causes of death: Pulmonary hypertension, pulmonary fibrosis. • Highest mortality among connective tissue diseases; no cure.

ETIOLOGY/RISK FACTORS

The exact inciting cause of scleroderma is unknown, but genetic, environmental, and infectious causes have been postulated. PHYSIOLOGY/PATHOPHYSIOLOGY

• Scleroderma is a multisystem connective tissue disease with variable clinical presentation. It is characterized by inflammatory processes that result in functional and structural abnormalities of small blood vessels:

– Tissue fibrosis results from fibroblast activation and excessive production of extracellular matrix (collagen deposition); this is the hallmark of the disease – Smooth muscle proliferation with impaired relaxation – Vessel damage – Platelet aggregation with luminal obliteration – These changes affect the myocardial, renal, and GI vascular beds

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Management should focus on the severity of organ system involvement. • The airway should be carefully examined; patients may have a limited mouth opening as well as oral and nasal telangiectasias that can cause profuse bleeding if traumatized. • Pulmonary function should be assessed as pulmonary fibrosis can lead to restrictive lung disease. • Cardiac status should be assessed for fibrosis of the conduction system and pulmonary hypertension.

PREOPERATIVE ASSESSMENT SYMPTOMS

Swelling of hands and feet, joint contractures, tight facial skin, heartburn, fatigue, shortness of breath History

• Organ system involvement and severity of disease: Skin, heart, lung, kidney, GI tract, thyroid • History of anti-inflammatory use (corticosteroids, immunomodulators) • GERD symptoms and medications

Signs/Physical Exam

Edema of hands and feet, sclerodactyly, calcinosis, Raynaud’s phenomenon, telangiectasias, dyspnea, dysphagia, weakness, weight loss MEDICATIONS

• Dihydropyridine calcium channel blockers (amlodipine), nitrates, and alpha-adrenergic blockers are given to improve vascular flow. • Cyclophosphamide can be given to slow the progression of pulmonary fibrosis. • Prostaglandins are often given for severe pulmonary hypertension. • Immunomodulators and corticosteroids can be given to help treat myositis and alveolitis in certain patients. • Antiplatelet therapy and anticoagulation have been used for patient with severe Raynaud’s phenomenon.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC to assess for anemia • Complete metabolic panel to assess for renal impairment • Coagulation studies if the patient has malabsorption (decreased vitamin K-dependent clotting factors) or liver disease • ECG to assess for conduction abnormalities • CXR, ABG if significant pulmonary impairment • Type and screen or type and cross if anemia is present. • Pulmonary function test if lung disease is severe (typical results for restrictive lung disease include low FVC, low FEV1, and elevated FEV1/FVC) • Stress test, echocardiogram, etc. if cardiac involvement is significant. • Thyroid function tests if thyroid disease is present.

CONCOMITANT ORGAN DYSFUNCTION Scleroderma can affect multiple systems:

• Nervous system: Neuropathies due to thickened nerve sheath connective tissue (carpal tunnel syndrome, trigeminal neuralgia) • Cardiac: Conduction abnormalities; cardiac dysfunction related to systemic and pulmonary hypertension (e.g., congestive heart failure); pericarditis, pericardial effusions; coronary vasospasm • Respiratory: Diffuse interstitial pulmonary fibrosis leading to decreased lung compliance; aspiration pneumonitis; chest wall restriction; weakness • Renal: Renal dysfunction due to accelerated hypertension • GI: Hypomotility of the esophagus and small intestines, which can be accompanied by bacterial overgrowth with resultant malabsorption; xerostomia (dry mouth) or Sjögren’s, esophagitis; GERD and Barrett’s esophagitis; primary biliary sclerosis; esophageal strictures; esophageal adenocarcinoma • Musculoskeletal: Arthritis; myopathy, myositis • Endocrine: Hypothyroidism • Hematologic: Anemia occurs due to malabsorption of iron, vitamin B12, and folate. • Vascular: Raynaud’s phenomenon, digital ischemia, and ulcers • Cutaneous: Sclerodactyly; edema of the hands and feet; skin tightening; calcinosis; telangiectasias; contractures CIRCUMSTANCES TO DELAY/CONDITIONS

Significant cardiac arrhythmias, active congestive heart failure, pericardial effusion; acute renal failure; high aspiration risk in patients with full stomach CLASSIFICATIONS

• Localized scleroderma: Involvement is confined to the skin • Limited systemic sclerosis/scleroderma: Cutaneous manifestations mainly affect the hands, arms and face; CREST syndrome—Calcinosis, Raynaud’s phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasias • Diffuse systemic sclerosis/scleroderma: Rapidly progressing, affects widespread areas of skin and at least one internal organ

TREATMENT PREOPERATIVE PREPARATION Premedications

• Aspiration prophylaxis with antacid, H2-receptor antagonist, and/or metoclopramide • Antisialagogue if fiberoptic intubation planned • Anxiolysis • Stress dose steroids should be considered if the patient has been treated for more than 2 weeks within the past 6–12 months to avoid manifestations of adrenal insufficiency. Steroids with glucocorticoid and mineralocorticoid activity should be administered. INTRAOPERATIVE CARE Choice of Anesthesia

• Regional anesthesia can be technically difficult due to skin and joint changes. Additionally, use caution with regional techniques if patients are on antiplatelet/anticoagulation therapy or if coagulation studies are abnormal. • Avoid drugs that are cleared by the kidneys or use reduced doses if renal impairment is present Monitors

• Standard ASA monitors • Avoid orogastric and nasogastric tubes, esophageal stethoscope with esophageal strictures • Avoid nasal or oral manipulation in patients with telangiectasias • Foley catheter for assessment of urine output, especially in patients with renal impairment • Use caution with invasive peripheral arterial monitoring as patients have vasomotor instability (Raynaud’s phenomenon) • Placement of IVs, central venous catheters, etc. can be challenging due to skin changes.

INDUCTION/AIRWAY MANAGEMENT

• Induction agents can result in profound hypotension due to vasomotor instability and contracted intravascular volumes. • Contracted skin around the mouth can result in limited mandibular range of motion and mouth opening; an awake fiberoptic intubation should be considered. • Normal airway exam: Consider a rapid sequence intubation as patients are at high risk for aspiration due to relaxed lower esophageal sphincters, dysmotility, etc. Perform gentle laryngoscopy to avoid disrupting telangiectasias. Maintenance

• Caution with positioning and tape for IV sites, ETT, and eyes due to skin sensitivity. • Avoid disturbances that can increase pulmonary vascular resistance (hypoxemia, hypercarbia, acidosis, etc.). • Positive pressure ventilation is often necessary due to restrictive lung disease. • Increased FiO2 and PEEP is often needed due to impaired diffusion capacity.

• Avoid hypothermia. Use convective blanket warmers, fluid warmers, and maintain a warm room temperature to avoid peripheral vasoconstriction. • Intractable intraoperative hypotension may be due to adrenal insufficiency, treat with stress dose steroids.

EXTUBATION/EMERGENCE

• Postoperative ventilation may be required if lung disease is severe. • Consider reversing nondepolarizing muscle relaxants to avoid postoperative weakness. • Careful observation for respiratory depression associated with opioids and other sedatives.

FOLLOW-UP BED ACUITY

• Telemetry if cardiac involvement is significant • Intensive care unit if the patient requires postoperative ventilatory support

MEDICATIONS/LAB STUDIES/CONSULTS • Consider postoperative ECG • CXR if signs of CHF are present • CBC

COMPLICATIONS

Aspiration pneumonitis, postoperative ventilation, weakness, cardiac arrhythmias

REFERENCES

1. Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009;360(19):1989– 2003. 2. Abraham DJ, Krieg T, Distler J. Overview of pathogenesis of systemic sclerosis. Rheumatology. 2009;48 (Suppl 3):iii3–7. 3. Roberts JG, Sabar R, Gianoli JA. Progressive systemic sclerosis: Clinical manifestations and anesthetic considerations. J Clin Anesth. 2002;14(6):474–477. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary hypertension • Difficult airway • Raynaud’s syndrome

CODES ICD9 710.1 Systemic sclerosis ICD10

M34.9 Systemic sclerosis, unspecified

CLINICAL PEARLS

• May present with challenging airways; prepare for an awake fiberoptic intubation. • Determine the extent of organ system involvement, obtain appropriate labs and studies to further assess severity of disease, and treat appropriately. • IV access can be difficult to obtain due to swelling and contractures. • Postoperative ventilation is often necessary if the patient has significant lung disease.

SCOLIOSIS REPAIR Chris A. Steel, MD Nina Singh-Radcliff, MD

BASICS DESCRIPTION General

• Scoliosis is a lateral and rotational deformity of the spine with a Cobb angle >10°. The angle is measured by drawing a parallel line from the superior border of the most displaced caudal vertebral body and then a second line is drawn parallel to the inferior border of the most displaced cephalad vertebral body. Perpendicular lines to both are drawn and the intersecting angle is measured. • Types of scoliosis include idiopathic or acquired, congenital, neuromuscular (DMD is the most common disorder), myopathic, traumatic, and tumor-related disorders. Idiopathic or acquired scoliosis is the most common cause of scoliosis as well as the most common indication for surgery because it often involves lateral curvature and rotation of the thoracic and lumbar spine along with vertebra and rib cage deformity. Additionally, it is commonly performed as a staged anterior and posterior procedure. • Conservative treatment involves a brace and observation. Surgery can prevent curve progression and correct the deformity; and is indicated when there is rapid progression or the curvature is >40° in the lumbar spine or >50° in the thoracic spine. With increased curvature, rotation progresses and the chest cavity narrows; this can result in restrictive lung diseases, respiratory insufficiency, pulmonary hypertension, and in severe cases, cor pulmonale. • Posterior approach involves a midline incision followed by dissection of subcutaneous tissue and muscle in order to provide adequate exposure of the spine. Instrumentation with pedicle screws or laminar hooks is inserted to stabilize the spine; rods are then used to reduce the curvatures and realign the spine. For severe deformities, additional, complicated deformity correction maneuvers are performed such as vertebral column resections (VCRs) or pedicle subtraction osteotomy (PSO). Bone graft is placed over the posterior elements to create fusion. • Anterior approach is utilized when the deformity is primarily at the thoracolumbar junction (T12-L1). One lung ventilation (OLV) or left side rib removal may aid with thoracic exposure. A vascular surgeon is usually present to aid with surgical exposure due to the concern of great vessel lacerations. Additionally, a chest tube is typically placed if a thoracotomy is performed. • Anterior spinal fusion may be performed in conjunction with either the posterior or lateral approach to improve reduction in the curve and enhance fusion. This technique is utilized in patients with severe deformities or who are still growing (anterior column will continue to grow and reduction would be affected). After the disc is removed, bone graft is inserted

into the disc space to facilitate fusion and maintain proper distance between vertebrae. Stabilizing screws and rods can be placed into the lateral vertebral body to improve alignment and assist fusion.

POSITION

• Prone for posterior approach. Shoulders should be abducted <90° and elbows flexed <90°, padded, and ulnar nerves free. Eyes and nose should be protected and free of pressure; consider using Prone-View, Gardner-Wells tongs, or Mayfield head holder. Breasts and genitalia should be appropriately padded. Use of a spinal frame allows the abdomen to hang free and without IVC compression. The neck should be kept midline and neutral in a slight reverse Trendelenburg position (∼30°). • Supine for anterior approach with arms tucked, padded, and ulnar nerves free. • Lateral decubitus position for a transthoracic or thoracoabdominal approach. Adequate padding and an axillary roll should be placed.

Incision

Length depending on the number of levels involved. APPROXIMATE TIME

Approximately 1.5–2.5 hours for a single level; add 1 hour for each additional level. EBL EXPECTED

300–5,000 mL; variable and based on the number of levels involved, the surgeon’s skills/dexterity, the use of antifibrinolytics (e.g., tranexamic acid or EACA), and controlled hypotension. HOSPITAL STAY

Approximately 5–7 day admission

SPECIAL EQUIPMENT FOR SURGERY

• C-arm fluoroscopy or O-ARM. Require appropriate radiation protection. • OSI table with Jackson Frames, or Wilson Frames. • Cell saver • Bone graft (autolograft, allograft, and BMP) • Neuromonitoring computer and personnel for monitoring motor-evoked potentials (MEPs), somatosensory-evoked potentials (SSEPs) and electromyography (EMG).

EPIDEMIOLOGY Prevalence

In the US: ∼50,000/year are performed Prevalence

• Adults: 1–15% of the population • Adolescents: 1–4% of the population (idiopathic disease comprises 60–70% of cases)

Morbidity

• Neurologic deficits: 1–5% with 0.37% incidence of major neurologic complications (up to 11% following PSO); substantial blood loss: 1–5%; pneumothorax: 1–5%; intraoperative awareness with explicit recall: 0.1–0.2%; visual field defects and vision loss: 0.03–0.1% • Pulmonary embolism, including venous air embolism (VAE) and fat embolism, postoperative wound infection, atelectasis and pneumonia, dural lacerations, CSF leaks • Failure to fuse, hardware fracture, bone graft migration are possible.

Mortality

Rare (0–0.5%)

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Positioning for prone, supine, and lateral approaches can prove challenging and require meticulous care. • Patients may have restrictive lung disease and in severe cases pulmonary hypertension or cor pulmonale. • Airway management may be affected by limited range of motion and cervical scoliosis and kyphosis. • Neuromonitoring. MEPs, SSEPs, and EMG require modification of anesthetic technique to optimize quality of results. Additionally, intraoperative “wake-up testing” and postoperative neurologic assessment require techniques that allow for rapid awakening. • Controlled hypotension may be beneficial in healthy patients to reduce bone bleeding. Additionally, isovolemic hemodilution can reduce the number of red blood cells (RBCs) lost and cell saver can decrease exposure to donor blood products.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Pain, paresthesia, and weakness in lower extremities. • Lower back pain (LBP)

History

• No improvement with conservative therapy. • Chronic pain medications • Comorbidities increase with age

Signs/Physical Exam

Preexisting sensory and motor deficits should be reviewed and documented MEDICATIONS

Pain patches, pain medications

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, CBC, PT/PTT/INR, CXR, EKG, and PFT are routine tests. Type and cross at least two units of packed RBCs.

• Spine X-ray, MRI, and CT scan are often performed prior to surgery. • TEE or stress test may be considered depending on comorbidities and/or functional status.

CONCOMITANT ORGAN DYSFUNCTION

• Restrictive lung disease, respiratory insufficiency, and pulmonary hypertension. • Cardiomyopathy, congenital heart disease, and cor pulmonale. • Chronic pain syndrome.

TREATMENT PREOPERATIVE PREPARATION Premedications

Anxiolysis and analgesia as needed

SPECIAL CONCERNS FOR INFORMED CONSENT

• Smoking cessation. Nicotine inhibits bone-growing cells and reduces successful fusion. • Patient should be instructed how to correctly use incentive spirometry and PCA. • Discuss the potential of an intraoperative wake-up test; consider a rehearsal.

ANTIBIOTICS/COMMON ORGANISMS

3rd generation cephalosporin for skin organisms

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia • Partial or total intravenous anesthesia (TIVA) to optimize neuromonitoring.

MONITORS

• Arterial line may be considered based on anticipated blood loss, comorbidities, and extent of controlled hypotension. • Central line may be considered to aid with assessing intravascular volume status as well as provide postoperative TPN. • Temperature-sensing Foley catheter. • SSEPs. Stimulation of a peripheral nerve with subsequent recording of the stimulus over the sensory cortex allows for the assessment of the posterior spinal cord and provides an objective assessment of the central and peripheral nervous systems. Both upper and lower extremity SSEPs should always be monitored. Upper extremity SSEP data would be sensitive to any upper extremity ischemia due to malposition or inadequate padding in the prone position. Volatile agents at a MAC >0.5 decrease the amplitude and increase the latency of the waveforms. • EMG. Spontaneous EMG is used to identify nerve root irritation during lumbar procedures (such as decompressions or TLIFs). Triggered EMG is used to evaluate the proper placement of pedicle screws. Muscle relaxant should be allowed to wear off prior to the start of EMG monitoring.

• Transcranial electrical motor-evoked potentials (TCeMEPs or MEPs). Stimulation of the motor cortex through the skull via electrodes placed into the scalp. Responses are recorded from muscles of the upper extremity and lower extremity assessing the entire motor pathway from cortex to muscle contraction. TIVA is the optimal technique for MEP monitoring. A bite block must be placed between the patient’s back teeth to prevent tongue laceration due to jaw clenching with stimulation.

INDUCTION/AIRWAY MANAGEMENT

• A limited range of motion may preclude the sniffing position; consider having a video laryngoscope or fiberoptic bronchoscope (awake or asleep) to utilize for the initial attempt at airway management. • ETT should be carefully secured to prevent self-extubation particularly in lateral and prone positioning. Consider No-Sting Skin-Prep or Benzoin to enhance adhesiveness of the tape followed by Op-Sites to waterproof from sweat, saliva, or other secretions. • Neuromuscular blockade is contraindicated when EMG or MEPs are monitored. Succinylcholine (Sux) or small dose of nondepolarizing muscle relaxants may be utilized to optimize intubating conditions and will wear off quickly. However, succinylcholine should not be used in patients with neuromuscular (DMD) scoliosis.

MAINTENANCE

• Confirm that the head is supported and kept in the midline/neutral position. • MEPs and SSEPs have improved reliability with the use of partial or total IV drug administration. Propofol is often utilized along with volatile/N2O <0.5 MAC, narcotic

(remifentanil, sufentanil), and/or other sedative/analgesic (dexmedetomidine, ketamine). The goal is to maintain a steady state, particularly during times where injury may occur (e.g., PSO and instrumentation), and avoid bolusing that may cause significant reductions in monitoring data. Immediate action should be taken for any significant data change; all technical, physiologic, and anesthetic factors should be quickly ruled out. • Critical to maintain an adequate level of anesthesia, as sudden movements can result in danger to the patient (bucking, coughing). • Temperature. Convection warming blankets, fluid warmers, and warmed blood products should be applied and administered. Hypothermia can affect coagulation, hinder awakening, cause arrhythmias, and increase pulmonary vascular resistance. • Fluid management. Blood loss may be significant. Autologous blood transfusion strategies (cell saver, isovolemic hemodilution) and controlled hypotension are often implemented. Coagulopathies may develop and transfusion with FFP may be necessary. • “Wake-Up” testing may be performed if neurological monitoring suggests the possibility of nerve damage, particularly while instrumenting or reducing the curvature. Extubation/Emergence

• Prepare for a fast and smooth emergence for neurologic exam. • Consider 30° reverse Trendelenburg position to avoid passive aspiration.

FOLLOW-UP

BED ACUITY

• Postoperative care involves acute pain management, removal of drains, neurological assessment, and monitoring for hematoma. • Ward/Telemetry or ICU if complex spinal procedure, substantial blood loss, significant comorbidities, or frequent neurological testing needs to be done. • Total recovery may take several months. Most patients are out of bed and start rehabilitation on POD 1, and are discharged home in a week.

Analgesia

• Significant pain may be expected for up to 4 days postoperatively. Implement a multimodal approach using PCA, anxiolytics, and muscle relaxants to control spasm. • Thoracic epidural catheter (TEC) placement may be performed intraoperatively by the surgeon and can significantly aid with the management of postoperative pain.

COMPLICATIONS See Morbidity PROGNOSIS

Relief of leg pain in the majority of patients (>80%), and relief of LBP in most of patients (60–70%).

REFERENCES

1. Buchowski JM, et al. Neurologic complications of lumbar pedicle subtraction osteotomy. Spine. 2007;32 (20):2245–2252. 2. Padberg AM, et al. Intraoperative electrophysiologic monitoring: Consideration for complex spinal surgery. Neurosurg Clin N Am. 2006;17:205–226. 3. Raw DA, et al. Anesthesia for spinal surgery in adults. Br J Anaesth. 2003;91(6):886–904. 4. Ornstein E, Berko R. Anesthesia techniques in complex spine surgery. Neurosurg Clin N Am. 2006;17:191–203. See Also (Topic, Algorithm, Electronic Media Element)

• Cell salvage • Somatosensory and motor-evoked potentials (SSEP/MEPs) • Isovolemic hemodilution • Controlled hypotension

CODES ICD9 • 737.30 Scoliosis [and kyphoscoliosis], idiopathic • 754.2 Congenital musculoskeletal deformities of spine ICD10

• M41.9 Scoliosis, unspecified • M41.20 Other idiopathic scoliosis, site unspecified • Q67.5 Congenital deformity of spine

CLINICAL PEARLS

• TIVA and avoidance of nondepolarizing muscle relaxants can enhance intraoperative neuromonitoring. Its goal is to provide early identification of potential neurological injury to avoid neurological deficits postoperatively. • Prepare for massive blood loss with adequate fluid replacement with IV fluids (colloid and crystalloid), blood loss reduction strategies, and transfusion of blood products. • Ensure a smooth and quick emergence for neurological exam.

SEIZURE DISORDERS Wendy HP Ren, MD, FAAP

BASICS DESCRIPTION

• Seizures are symptoms of underlying neurologic disorders that may be – Genetic – Traumatic – Metabolic – Infectious – Malignant – Pharmacologic – Idiopathic • Epilepsy syndromes are based on clinical descriptions and etiologies, such as age of onset, seizure types, EEG features, and other factors such as family history. Seizures occur as part of an epileptic syndrome; thus, identification of the syndrome helps determine the appropriate therapy and the prognosis. • Epileptics may need anesthesia for routine procedures as there is a higher incidence of individuals with intellectual and developmental disabilities (mental retardation, cerebral palsy, autism, and psychiatric and behavioral disabilities). Anesthesia and or sedation may be used to facilitate procedures such as dental restorations, EEGs, and other imaging studies. Additionally, the incidence of epilepsy increases with the severity of disability. • Well-controlled epileptics may also present for unrelated surgical procedures. Postoperative seizures may be seen secondary to missed antiepileptic drugs (AEDs), stress, sleep deprivation, anesthetic drugs, or metabolic derangement. EPIDEMIOLOGY Prevalence

• In the US, 100,000 people have a new onset seizure each year • Greater in the elderly

Prevalence

• In the US, 2,000,000 persons have epilepsy, of which 300,000 are children under the age of 14. • Approximately 10% of the population will have at least one seizure at some point in their life. Morbidity

• In children it can lead to neurologic impairment and developmental delay. • Driving and operating machinery should be avoided. • Coma

Mortality

Uncontrolled, prolonged seizure activity can result in death. ETIOLOGY/RISK FACTORS

• Seizures are symptoms of underlying disorders that may be genetic, traumatic, metabolic, infectious, malignant, pharmacologic, or idiopathic. • Diagnosis and management can be challenging for both the family and healthcare providers, partly because the incidence of epilepsy is higher in the intellectually and developmentally disabled population.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Seizure classifications are based on location, clinical symptoms, spread, and duration. Appropriate classification of seizure disorders is crucial in providing effective treatment and prognosis. • Alterations in GABA neurotransmission have been implicated in epilepsy, and pharmacotherapy is targeted to affect central nervous system receptors or neurotransmitter activity.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Epileptic patients may present for – Diagnostic procedures. Require preservation of the EEG; epileptic activity required. Many of these procedures require a cooperative patient, and at times, immobility to obtain optimal results. The pediatric, as well as neurologically impaired, population often requires sedation or general anesthesia. Effects of sedatives/anesthetics on the quality of the diagnostic study must be taken into account. – Nonrelated and routine procedures. Patients with developmental disabilities are not only more challenging to treat in the perioperative period, due to a lack of cooperation, but often have the greatest likelihood of polypharmacy, drug interactions, and unpredictable sedation efficacy. • AEDs and anesthetic agents – Enzyme induction. Antiepileptic medications may upregulate enzymes that are responsible for drug metabolism and consequent termination of action (e.g., P450). This can result in rapid metabolism of certain anesthetic drugs and muscle relaxants. – Side effects. Include drowsiness, sedation, somnolence, and lethargy, which may have an additive effect when combined with the anesthetic. A thorough evaluation prior to administration of anesthetics with these factors in mind can help guide the choice of anesthetics as well as establish appropriate post-sedation monitoring and discharge criteria. • EEG and epileptic activity. Anesthetic agents may have proconvulsant effects, anticonvulsant effects, or pro- and anticonvulsant effects depending on the dose and clinical situation.

PREOPERATIVE ASSESSMENT SYMPTOMS

Description of seizure type(s), post-ictal symptoms History

• Seizure history: Frequency, last seizure, precipitating events, loss of consciousness, treatment efficacy, comorbidities, physical and developmental disabilities/limitations • Perioperative seizures or complications.

Signs/Physical Exam

• Level of consciousness, awareness, and activity to establish discharge criteria. • Airway exam. Physical limitations for airway management and operative positioning.

TREATMENT HISTORY

Nonmedication therapy may include a ketogenic diet, vagal nerve stimulator implant, or craniectomy. MEDICATIONS

• Epilepsy has many causes, and treatment is based on the diagnosis that is derived from a compilation of findings. Evaluation of patients with a single, unprovoked seizure must take into account the likely risk of seizure recurrence, patient age, level of activity, personal preference, and potential side effects of antiepileptic drugs. Only after a second seizure is the diagnosis of epilepsy made and routinely treated with AEDs. • Determine the last dose, symptoms from missed doses. • AEDs frequently induce the P450 enzyme system, so patients may require increased dose and frequency of nondepolarizing neuromuscular blockers. • Gabapentin can compound analgesic effects • Valproate side effects: Sedation, nausea/vomiting, rashes, scleroderma, systemic lupus erythematosus, hepatic failure, thrombocytopenia • Carbamazepine side effects: Anemia, leucopenia, hyponatremia • Phenytoin side effects: Altered thyroid function

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

Despite potential side effects from AEDs, routine labs are not generally indicated CONCOMITANT ORGAN DYSFUNCTION

• Usually related to AED side effects • Increased incidence of depression and other psychiatric morbidities. In multiple studies, improvement in quality of life is related to seizure control. CIRCUMSTANCES TO DELAY/CONDITIONS

• Reports of increased seizure activity or new onset of seizure type (nontypical seizure) • Prolonged NPO status (missed AED dose) or concurrent illnesses may increase seizure risk.

CLASSIFICATIONS Based on

– Location: – Generalized seizures are due to abnormal activity on both sides of the brain – Focal (partial) seizures begin in a specific area of the brain and may be motor, sensory, or both. • Symptoms: – Tonic: Stiffening – Clonic: Rhythmic jerking – Combined tonic-clonic – Myoclonic – Absence: Staring episode – Atonic: Loss of muscle tone • Spread: – Partial seizures that result in a loss of awareness are termed “complex partial” – If it evolves to include both hemispheres of the brain, it is termed “complex partial with secondary generalization.” • Etiology allows for further subdivisions: Idiopathic (genetic), cryptogenic, and symptomatic.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines should be avoided for diagnostic procedures. • Ketamine may activate epileptogenic foci. • Dexmedetomidine may be administered IV or intranasally for sedation and is devoid of EEG affects. • Consider IV preparation of AED if necessary • Consider a neurology consultation for management of perioperative seizure or anticipated prolonged NPO status. Special Concerns for Informed Consent

Patients and family should be made aware of the potential for perioperative seizures, postictal delayed awakening, and prolonged postanesthesia monitoring. INTRAOPERATIVE CARE Choice of Anesthesia

• Dependent on the procedure, comorbidities, need for akinesis, and risk for aspiration. • Diagnostic procedures require avoidance of anticonvulsant anesthetics.

Monitors

• Standard ASA monitors • Consider EEG monitoring if there is a high risk of undetectable seizure activity (e.g., use of muscle relaxation in a high risk patient) Induction/Airway Management

• Seizures are most common during emergence and induction, as rapid changes in brain concentrations of anesthetic occur. • Consider the risk of aspiration in patients with severe disabilities; a cuffed endotracheal tube may be appropriate.

Maintenance

• Anesthetic technique is dependent on the procedure (diagnostic, therapeutic, nonrelated). • Anticonvulsant anesthetics: Volatile anesthetics, propofol, thiopental, and etomidate. • Neutral anesthetics: Dexmedetomidine and choral hydrate (sedation procedures) • Proconvulsant properties – A rapid rise in sevoflurane. – Enflurane and methohexital may activate epileptogenic foci. – Ketamine may result in subcortical epileptogenic stimulation. – Etomidate and propofol have both been implicated in seizure-like movements. – High doses of opioids such as remifentanil, alfentanil, sufentanil, and fentanyl are also associated with seizure activity.

Extubation/Emergence

Seizures may occur during emergence due to rapid changes in anesthetic brain concentrations.

FOLLOW-UP BED ACUITY

Consider intensive care if the patient has uncontrolled seizures in the perioperative period. MEDICATIONS/LAB STUDIES/CONSULTS

• Consider a neurology consult to manage anticonvulsants if the patient cannot tolerate their home regimen or if seizure disorder is not controlled. • If the patient has a seizure, check for glucose and electrolyte derangements. Consider checking anticonvulsant levels; however, therapeutic levels may not be clinically relevant and consultation by a neurologist is preferable. • Discharge: A caregiver who knows the patient’s baseline mental status is helpful for discharge planning.

COMPLICATIONS

• Perioperative seizure • Consider postictal unconsciousness if delayed awakening. Consider delaying extubation in the seizing patient to provide airway protection.

REFERENCES

1. Browne TR, Holmes GL. Epilepsy. N Engl J Med. 2001;344:1145–1151. 2. Drugs for epilepsy. Treat Guidel Med Lett. 2003;1:57–64.

3. Kohrman MH. What is epilepsy? Clinical perspectives in the diagnosis and treatment. J Clin Neurophysiol. 2007;24:87–95. 4. Modica PA, Tempelhoff R, White PF. Pro- and anticonvulsant effects of anesthetics (Part I and II). Anesth Analg. 1990;70:303–315, 433–444. 5. Ren WH. Anesthetic management of epileptic pediatric patients. Int Anesthesiol Clin. 2009;47(3):101–116. 6. Smith D, Minshall I. Drug management of epilepsy. Practitioner. 2003;247:19–22, 24, 27– 28 passim. See Also (Topic, Algorithm, Electronic Media Element) • Perioperative seizures • Hypoglycemia • Anesthesia for neuroradiology • Intubation and extubation criteria

CODES ICD9 • 345.90 Epilepsy, unspecified, without mention of intractable epilepsy • 780.39 Other convulsions ICD10 • G40.909 Epilepsy, unsp, not intractable, without status epilepticus • R56.9 Unspecified convulsions

CLINICAL PEARLS

• Anaesthetists need to be aware of the common adverse effects of AEDs • Perioperative seizures occur most commonly during induction and emergence. • Many anesthetics have both proconvulsant and anticonvulsant properties. Generally, most anesthetics are anticonvulsant at high doses except opioids.

SEPTIC SHOCK Anahat Dhillon, MD Sumit Singh, MD

BASICS DESCRIPTION

• Sepsis describes a documented infection (culture or Gram stain of a normally sterile body fluid for pathogenic organism or focus of infection identified by visual inspection) and two or more manifestations of the systemic inflammatory response syndrome: – Temperature >38°C or <36°C – Heart rate >90 beats/min – Respiratory rate >20 breaths/min or paCO2 <32 mm Hg – WBC >12,000/μL, <4,000/μL, or >10 immature (band) forms. • Septic shock is a severe form of sepsis and involves hypotension despite adequate resuscitation, end-organ hypoperfusion (e.g., lactate >2 mmol/L), and organ dysfunction (e.g., urine output <0.5 mL/kg). It has features of high output cardiac failure and distributive shock. EPIDEMIOLOGY Prevalence

• ∼50–95 cases per 100,000 annually • In the US, >750,000 cases/year

Morbidity

Complications include renal failure (50%), disseminated intravascular coagulopathy or DIC (38%), and acute respiratory distress syndrome (ARDS) (18%). Mortality

In the US, ∼200,000/year

ETIOLOGY/RISK FACTORS

• Gram-positive bacteria (30–50%): Staphylococcus pyrogenase, S. pneumonia, S. aureus • Gram-negative bacteria (25%): Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenza • Fungal: Candida albicans • Anaerobes: Clostridium perfringens • Older individuals (>65 years) have increased comorbidities, impaired immunological response to infections, and increased exposure to potentially resistant organisms in nursing homes, all contributing to increased mortality. They account for ∼60% of severe sepsis cases. • Immunocompromised patients (neoplasms, AIDS, hepatic or renal failure).

• Compared to community-acquired infection, nosocomial infections have a higher mortality rate (10% versus 15%). • Community acquired pneumonia (CAP) patients will develop severe sepsis in 48% and septic shock in 5% of cases. • Source of sepsis also determines outcomes, with urosepsis having a 30% mortality rate compared to 55% if the source was pulmonary, GI or unknown.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The aim of normal inflammation is to locally contain the spread of infection. However, in certain cases, the inflammatory process spreads across the locally infected area, invades the bloodstream, and causes a generalized response, known as sepsis. • Sepsis is a complex, malignant intravascular inflammation. The lipopolysaccharide of Gramnegative bacteria and the peptidoglycan of Gram-positive bacteria bind to cell receptors (CD 14, TLR-2,4) and induce production of pro-inflammatory cytokines (tumor necrosis factor α [TNF α], interleukin-1 [IL-1]), chemokines (ICAM-1, VCAM-1), and nitric oxide. The endothelium cells express adherence molecules that attract leukocytes and macrophages that in turn release more cytokines (TNF and ILs). TNF further stimulates production of other secondary inflammatory mediators, besides being self-stimulating (autocrine). Activation of the complement system, release of IL-1, 2, 6, 8, 10, platelet-activating factor, interferons, and eicosanoids result in recruiting more leukocytes and macrophages. These inflammatory mediators cause local vasodilation, hyperemia, and increased permeability resulting in protein rich edema. They also contribute to cellular injury. Other proposed mechanisms of cellular injury are apoptosis (programmed cell death) and ischemic damage. • Pattern recognition receptors (PRRs) recognize specific structures of microorganisms. In sepsis response, PRR such as toll-like receptors (TLR) are capable of sensing a wide range of organisms (bacteria, fungi, viruses and protozoa). Their activation leads to cellular activation and inflammatory response initiation. • Some cytokines (IL-6, IL-10) have an anti-inflammatory effect by inhibiting production of TNF α and IL-1. In a normal effective response to an infectious insult, the pro- and antiinflammatory responses balance each other out and the initial infectious insult is overcome. In certain cases, the initial infectious assault may be so severe and sufficient to produce sepsis. In another scenario, after the initial insult, the balance between pro- and antiinflammatory forces may not be established leading to a massive systemic inflammatory response, or a period of immune suppression.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Initiate therapy early. Intubation and mechanical ventilation, invasive monitoring, laboratory work, antibiotics, and treatment of hypoperfusion. • Intensive care unit (ICU) bundles may be carried out by the anesthesiologist in the ICU or continued into the perioperative period. They include – Identifying a specific anatomic site of infection within the first 6 hours. If intravascular devices are believed to be the source, they should be removed. – Broad-spectrum antibiotics should begin within 3 hours of ED admission and within 1 h of non-ED admission. However, blood cultures should be obtained prior to antibiotic administration.

– Measure serum lactate – Hypotension and/or elevated lactate should be treated with IV fluids. If unresponsive, vasopressors should be implemented to maintain a MAP >65 mm Hg. Achieve a CVP of >8 mm Hg, central venous oxygen saturation (ScvO2) >70%, or mixed venous oxygen saturation (SvO2) >65%. This may require pRBC transfusion or inotropy.

– Steroids (hydrocortisone 200–300 mg/day for 7 days) may be used in vasopressordependent shock. – Consider recombinant human activated protein C (rhAPC). Activated protein C normally regulates blood clotting, inflammation, cell death, and endothelial integrity. In sepsis the levels are reduced, and randomized controlled trials suggest that it can decrease mortality, especially in the first 24 hours in patients with APACHE score >25.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Fever, rigors, chills • Abdominal pain (if the source of sepsis is abdominal) • Mental status changes and confusion (especially if patient febrile or hypoxic)

History

• Look for preceding conditions: Intraabdominal sources (diverticulitis, Crohn disease, previous abdominal surgery, cholecystitis, subacute appendicitis), urosepsis (pyelonephritis, nephrolithiasis, congenital urological abnormalities, benign prostate hypertrophy, and previous urological surgeries). • Immunocompromised patients, diabetics, systemic lupus erythematosus (SLE), alcoholics, and steroid-dependent patients are at increased risk of bacteremia and sepsis. • Suspect IV line infections, especially when other sources of infection have been ruled out. Central venous lines >1 week are most commonly involved. Arterial lines are rarely involved and peripheral venous lines are almost never associated.

Signs/Physical Exam

• Hypotension, tachycardia, bounding pulse. Inflammatory mediators such as TNF α, not only cause a decrease in peripheral vascular resistance but also cause a myocardial depressant effect (septic cardiomyopathy). • Early stages: Warm flushed skin. Later stages: Cold, mottled extremities • Oliguria or anuria • Hypoxia, tachypnea, respiratory alkalosis • Hyperthermia or hypothermia

TREATMENT HISTORY

Intubation and mechanical ventilation. There is an increased work of breathing secondary to increased minute ventilation and airway resistance, and decreased lung compliance. Additionally, patients may have developed ALI/ARDS. MEDICATIONS

• Vasopressors: Norepinephrine, dopamine, phenylephrine, vasopressin. No definitive evidence of superiority has been demonstrated. • Antibiotics: Broad-spectrums include vancomycin in combination with a 3rd-generation cephalosporin or carbapenem. If pseudomonas is suspected, vancomycin with two antipseudomonal agents (e.g., ceftazidime, meropenem, ciprofloxacin, and meropenem) are used.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Chem 10 to evaluate renal function, CBC plus differential, lactic acid levels • Arterial blood gases (ABGs) to assess acid base abnormality and oxygenation and any A-a gradient. • Mixed venous saturation • Procalcitonin is an early biomarker of sepsis that has been found to be most sensitive and specific in recent studies. • Bedside echocardiography can reveal or rule out cardiogenic causes, as well as guide resuscitation.

CONCOMITANT ORGAN DYSFUNCTION Underlying sources; see above

CIRCUMSTANCES TO DELAY/CONDITIONS

• Procedures should be limited to those absolutely necessary (source control) and that can potentially improve survival. • Prior to the OR, proper resuscitation with IV fluids, vasopressors, and early goal directed therapy should be done (MAP >65 mm Hg, CVP 8–12 mm Hg, adequate urine output, correction of acid base abnormality and lactic acidosis, and achieving a mixed venous oxygen (MVO2%) or ScvO2% >70%). • Patients in renal failure may need preoperative dialysis catheter placement followed by dialyses; intraoperative continuous veno-venous hemodialysis (CVVH) may be necessary.

TREATMENT PREOPERATIVE PREPARATION Premedications

• FFP, platelets, and cryoprecipitate may be considered in coagulopathic or thrombocytopenic patients. • Vasopressor drips should be prepared beforehand, in anticipation of hypotension. • Cautious administration of benzodiazepines and opioids; patients have minimal physiologic reserve and can get hypotensive or hypoxic. • H2 blocker or proton pump inhibitors for stress ulcer prophylaxis.

Special Concerns for Informed Consent

• Altered mental status may preclude consent • Anesthesia and surgery is extremely high risk • Need for additional invasive monitoring • Blood consent

INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia with ETT Monitors

• Arterial line: BP monitoring, titration of vasopressors, ABGs, glucose, and lactate levels. Respiratory variations provide a dynamic parameter of intravascular volume assessment and may be more accurate than CVP. • Central venous catheter: Pressures and ScvO2 can guide fluid therapy. Pulmonary artery catheters are not recommended for routine use in sepsis. • Sufficient IV access for volume resuscitation. • Core temperature monitoring, as pyrexia of sepsis may be offset by heat loss from the surgical field. Induction/Airway Management

• Rapid sequence intubation due to decreased gut motility (secondary to hypoperfusion). Succinylcholine can be used, provided that the patient is not hyperkalemic. Avoid when source of infection is intraabdominal; succinylcholine may release excessive amounts of K+. Rocuronium can be used in such cases. • Induction agent with cardiovascular stability such as etomidate or ketamine can be used. Etomidate use in sepsis has been debated because of its reversible adrenocortical suppression. However, no prospective randomized control trial has shown any increase in adverse effects with a single dose. • Be prepared to treat hypotension with fluid boluses and/or vasopressors

Maintenance

• Administer antibiotics within 30 minutes of skin incision. • Consider or continue steroid administration. • Consider benzodiazepines or scopolamine in patients who cannot tolerate the effects of volatile agents or hypnotics, to decrease the incidence of awareness under anesthesia. • Maintain normothermia and normoglycemic (80–150 mg/dL). • Maintain Hg levels between 7 and 9 g/dL and platelets above 50,000/μL. • Limit TV (6–8 mL/kg) and plateau pressure <30 cm H20.

Extubation/Emergence

Postoperatively mechanical ventilation is often continued into the ICU until the patient is more hemodynamically stable.

FOLLOW-UP

BED ACUITY

ICU care for monitoring of vital signs, narrowing of antimicrobial therapy as guided by the culture results, supportive care such as continuation of mechanical ventilation, vasopressors, dialysis, and early initiation of enteral nutrition. MEDICATIONS/LAB STUDIES/CONSULTS Infectious disease, nephrology as needed

REFERENCES

1. Angus DC, et al. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–1310.

REFERENCES

2. Baluch A, et al. Septic shock: Review and anesthetic considerations. Middle East J Anesthesiol. 2007;19(1):71–86. 3. Dellinger RP, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296–327. 4. Levy M, et al. The Surviving Sepsis Campaign: Results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010;36(2):222–231. 5. Schuerholz T, Marx G. Management of sepsis. Minerva Anesthesiol. 2008;74(5):181–195. See Also (Topic, Algorithm, Electronic Media Element) • Acute respiratory distress syndrome (ARDS)

CODES ICD9 785.52 Septic shock ICD10 R65.21 Severe sepsis with septic shock

CLINICAL PEARLS

• Fluids should be administered in septic shock until there is improvement in perfusion (or cardiac output). • Vasopressors and inotropes may be necessary to prevent fluid overload and pulmonary edema.

SHUNT, INTRAPULMONARY Eric Bolin, MD

BASICS DESCRIPTION

• Intrapulmonary shunt (IPS) occurs when blood passes through the lungs without acquiring oxygen. This results in the return of oxygen-poor venous blood to the left heart that mixes with well-oxygenated pulmonary venous blood. It may result from – Ventilation/perfusion abnormalities – Anatomical arteriovenous anastomosis • Normally the fraction of blood that passes through the lungs without acquiring oxygen is very low and therefore has no clinical significance. PHYSIOLOGY PRINCIPLES

• Intrapulmonary shunt (IPS). A right-to-left shunt results in a hypoxic shunt, whereas a leftto-right shunt does not. – Ventilation/perfusion shunting describes perfusion without ventilation; this is in contrast to dead space, which is ventilation without perfusion. A shunt may be relative or absolute; an absolute shunt occurs when ventilation is zero. – There are 4 lung zones: Zone 1 PA > Ppa > Ppv Zone 2 Ppa > PA > PPV

Zone 3 Ppa > PPV > PA

Zone 4 Ppa > PISF > Ppv > PA

PA = Alveolar pressure, Ppa = pulmonary artery pressure, Ppv = pulmonary venous pressure, PISF = pulmonary interstitial pressure

In zones 3 and 4, partial or complete alveolar collapse can result in relative or absolute shunt. • Intracardiac shunt, while anatomically distinct from IPS, can have the same net impact on oxygenation and may contribute to shunt fraction. Examples include ventral and atrial septal defects and a patent foramen ovale. Initially, the relatively higher pressures on the left side of the heart results in blood being shunted from left-to-right. However, with time, the increased blood flow through the pulmonary vasculature can result in overload, with consequent pulmonary hypertension. If the pulmonary pressures become high enough, shunt reversal may occur (blood flows from the right-to-left), thus converting a nonhypoxic shunt into a hypoxic shunt. Eisenmenger syndrome describes the combination of increased pulmonary pressures, cyanosis, and erythrocytosis from shunt reversal. • Hypoxic pulmonary vasoconstriction (HPV) refers to the normal physiologic constriction of pulmonary vasculature in response to hypoxia in an attempt to divert blood flow to well-

oxygenated regions of the lung. HPV improves oxygenation by improving V/Q ratios regionally, and reduces relative shunt. While HPV is an intrinsic physiologic mechanism that may improve oxygenation, it is important to note that volatile anesthetic agents inhibit HPV. This may contribute to increased shunt fraction under general anesthesia. • Shunt fraction/venous admixture. Describes the magnitude of IPS as a percentage of cardiac output that returns to the left atrium without being oxygenated; it is a physiologic concept. The shunt fraction/venous admixture may be thought of as the amount of venous blood that would have to be mixed with optimally oxygenated blood to account for the difference in oxygen content between the optimally oxygenated blood and the observed oxygen content. – The formula is derived from a two-compartment model of the lung. In the first compartment, all lung segments have a V/Q ratio of 1. In the second compartment, all segments have a V/Q ratio of 0. This formula is generally used with an FiO2 of 100% to conceptually eliminate lung units with very low V/Q ratios, or relative shunt; at an FiO2

of 1.0, these segments will oxygenate blood well. – Shunt fraction = QS/QT = (CcO2 – CaO2)/(CcO2 – CvO2) and is a composite of any and

all factors affecting oxygenation. The trend is more important than the absolute value. With respect to the two compartment model, the shunt fraction can be thought of as the perfusion of the compartment for which V/Q = 0. – Normal (physiologic) shunt fraction is ∼2–5% and occurs through anatomic shunts from the pleural, bronchiolar, and Thebesian veins.

ANATOMY

• Thebesian veins arise in the myocardium and empty into the left atrium. • Bronchial veins drain small bronchi, septa, and connective tissue in the lungs. Bronchial circulation returns to the left heart via the pulmonary veins. • Pleural veins drain the visceral pleura and return to the left heart via the pulmonary veins.

DISEASE/PATHOPHYSIOLOGY

• Processes that may contribute to the development of IPS include – Atelectasis in the perioperative period is the result of several factors. Anesthetic agents affect and impair the movement of the diaphragm and intercostal muscles (diaphragm allows cephaled invasion of the abdomen and the anteroposterior movement of the rib cage is affected). Supine and Trendelenburg positioning further accentuates these effects. Mechanical ventilation preferably delivers volume to nondependent lung spaces, whereas blood flow is greatest in dependent areas. In the postoperative period, pain can lead to “splinting,” or shallow respiration due to pain; optimal management requires sufficient pain control without oversedation. – Acute lung injury. A form of noncardiogenic pulmonary edema that is characterized by acute hypoxic respiratory failure and bilateral pulmonary infiltrates with resultant significant V/Q mismatch and resultant hypoxemia. ARDS is a subset of acute lung injury (2). – Congestive heart failure. Impaired cardiac pump function can result in “backup” into the right atrium and pulmonary vasculature. Initially, recruitment and dilation of the pulmonary vasculature occurs; this is followed by fluid extravasation into the interstitial

space and then entry into the alveoli. These processes impair alveolar expansion. – Consolidated pneumonia leads to alveoli being clogged with exudative material. Ventilation of these units is zero, representing a true shunt. • Hepatopulmonary syndrome (HPS) describes a triad of pulmonary vascular dilation, liver disease, and a defect in oxygenation. Pulmonary vascular dilation: – Increases flow through AVMs with a resultant increase in shunt fraction – Contributes to V/Q mismatching by increasing blood flow without a corresponding increase in ventilation (3). • Arteriovenous shunting describes direct vascular anastomoses between pulmonary arteries and veins. The magnitude of an arteriovenous shunt can be affected by changes in position and lung volumes. – Position. In the presence of an asymmetrical cranial to caudal distribution of pulmonary arteriovenous malformations (AVMs), changing posture may increase shunt fraction. The Trendelenburg position combined with predominantly basal AVMs will increase blood flow and shunt. – Lung volumes. Increases in lung volume increase the resistance in normal pulmonary blood vessels to a greater extent than AVMs. The result is an increase in blood flow through AVMs, and hence shunt fraction. This is consistent with increased lung volumes having no effect on shunt fraction in healthy patients free of AVMs (1).

PERIOPERATIVE RELEVANCE

• Saline contrast echocardiography can be used to diagnosis intracardiac shunting by injecting agitated saline into the venous circulation. The appearance of bubbles immediately in the left heart (1–2 cardiac cycles) is consistent with the presence of an intracardiac shunt. The delayed appearance of bubbles (4–8 cardiac cycles) is consistent with the presence of an IPS (3,4). • IPS caused by atelectasis under general anesthesia (V = 0 for atelectatic alveoli, representing a true shunt) may be improved significantly with strategies and maneuvers that increase alveolar size and assume a more favorable shape for exposure to pulmonary vasculature. – Intermittent postintubation or intraoperative application of high levels of PEEP (up to 15 cmH2O) and a tidal volume up to 18 cc/kg until a peak inspiratory pressure of 40 cmH2O is reached has been shown to decrease atelectasis. After recruitment, PEEP is maintained at 5 cmH20 to ensure that recruited alveoli remain open (5).

– Obese patients experience a profound decrease in lung compliance, decreased PaO2, and

increased PaCO2 relative to nonobese individuals. The application of PEEP at 10 cmH20

has been shown to significantly improve pulmonary mechanics and oxygenation (6). – Noninvasive positive pressure preoxygenation, when combined with a postintubation or intraoperative recruitment maneuver of 40 cmH20 for 40 seconds, patients exhibited

improved oxygenation and end expiratory lung volumes (7). • Absolute shunt. Atelectatic alveoli (fully collapsed, fluid filled, proteinaceous filled) are not ventilated. Thus, hypoxemia from these causes remains unresponsive to increased FiO2;

blood flow is not exposed to alveolar gases and therefore cannot be oxygenated. Conversely,

relative shunt occurs when ventilation is low but greater than zero; it remains responsive to increased FiO2. EQUATIONS

• Shunt fraction = QS/QT = (CcO2 – CaO2)/(CcO2 – CvO2) = <5% – CcO2 = oxygen content of ideal pulmonary end capillary blood – CaO2 = oxygen content of mixed arterial blood – CvO2 = mixed venous oxygen content

– Calculation of the shunt fraction via this equation requires a pulmonary artery catheter to obtain a mixed venous oxygen saturation, limiting the utility of this index. • Ventilation/perfusion = V/Q = (4 L/min)/(5 L/min) = 0.8. – Gross normal value for both lungs varies widely for individual lung units. • Ventilation perfusion ratio = VQI = (1 – SaO2)/(1 – SvO2)

– This formula substitutes saturation values for oxygen content because hemoglobin concentration is constant (therefore, oxygen content correlates with saturation).

REFERENCES

1. Ueki J, et al. Oxygen and 99mTc-MAA shunt estimations in patients with pulmonary arteriovenous malformations: Effects of changes in posture and lung volume. Thorax. 1994;49:327–331. 2. Rubenfeld GD, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353(16):1685–1693. 3. Rodriguez-Roisin R, et al. Hepatopulmonary syndrome – A liver-induced lung vascular disorder. N Engl J Med. 2008;358:2378–2387. 4. Castro P, et al. Intrapulmonary shunting associated with sildenafil treatment in a patient with idiopathic pulmonary arterial hypertension. Thorax. 2011 Epub ahead of print. 5. Tusman G, et al. Alveolar recruitment strategy improves arterial oxygentaion during general anesthesia. Br J Anesth. 1999;82:8–13. 6. Pelosi R, et al. Positive end-expiratory pressure improves respiratory function in obese but not in normal subjects during anesthesia and paralysis. Anesthesiology. 1999;91:1221–1231. 7. Futier E, et al. Noninvasive ventilation and alveolar recruitment maneuver improve respiratory function during and after intubation of morbidly obese patients. Anesthesiology. 2011;114:1354–1363. See Also (Topic, Algorithm, Electronic Media Element)

• Ventilation and perfusion mismatching • Pulmonary hypertension • Patent foramen ovale • Ventral septal defect • Atelectasis

CLINICAL PEARLS

• Increased IPS can cause significant hypoxemia during the perioperative period. Shunting due to atelectasis is a common cause of hypoxemia that can be treated and ameliorated with appropriate ventilator management. • Surgery should be avoided or minimized in the presence of conditions or disease processes that significantly increase shunt fraction and thereby result in hypoxemia. These conditions include but are not limited to acute lung injury, ARDS, pneumonia, and pulmonary edema. • Normal physiologic shunt, which is 2–5%, is functionally equivalent to an IPS, and is reflected in calculations of IPS.

SICK SINUS SYNDROME Adam M. Stuart, MD

BASICS DESCRIPTION

• Sick sinus syndrome (SSS) is characterized by abnormalities in the generation of cardiac impulses from the sinoatrial node (SAN). – Sinus bradycardia – Sinus arrest – Sinus exit block – SA and AV conduction disturbances – Chronic atrial tachyarrhythmias – Alternating episodes of atrial bradyarrhythmias and tachyarrhythmias (tachy-brady syndrome). • SSS is categorized into etiologies that are intrinsic or extrinsic to the SAN.

EPIDEMIOLOGY Prevalence

• Overall incidence has not been quantified • Accounts for at least 50% permanent pacemaker placement in the US.

Prevalence

• Increases with age (mean age = 68 years) • Occurs equally in both genders and without predominance in any one race

Morbidity

• Its association with advanced cardiovascular (CV) disease may carry a variety of coexisting conditions. • Associated with thromboembolism and/or stroke; chronic atrial fibrillation (a-fib), AV block; and complications of therapeutic anticoagulation Mortality

• Increased risk of sudden cardiac death • Following permanent pacemaker placement, 1–year mortality is 5–10% and 5–year mortality is 25–30%. This is, in part, attributable to comorbid CV disease. • Ventricular pacing is associated with higher mortality than atrial pacing alone. • Pacemakers in patients with tachy-brady syndrome have been shown to ameliorate symptoms of bradycardia and frequency of a-fib, but not improve survival. • Patients with only bradycardia have a better prognosis; their mortality is similar to that of the general population (1).

ETIOLOGY/RISK FACTORS

• Intrinsic etiologies – Most commonly caused by fibrosis of nodal tissue – Idiopathic (most common cause) – Cardiac: Chronic ischemia, infarction, myocarditis, pericarditis, cardiomyopathy – Autoimmune: Amyloid, sarcoid, SLE – Genetic: Familial SAN disorders, Friedreich’s ataxia, hemochromatosis – Infectious: Chagas, diphtheria, rheumatic disease – Neoplasm: Leukemia, metastatic disease – Pediatric: Congenital abnormalities • Extrinsic etiologies – Iatrogenic: Digitalis, calcium channel blockers, beta-blockers, sympatholytics, antiarrhythmics – Hypoxia – Electrolyte imbalance: Hyper/hypokalemia, hypoglycemia – Hyper/hypothyroid

PHYSIOLOGY/PATHOPHYSIOLOGY

• Idiopathic fibrosis of the SAN is the most longstanding hypothesis; however, other general mechanisms have been proposed and researched primarily in animal models. Intrinsic dysfunction is the result of failure to generate a sinus impulse and/or diminished travel of an impulse to surrounding myocardium. • Age-related remodeling of the cardiac extracellular matrix can affect cellular ionic currents and channels. • Familial condition has been linked to genetic mutations in genes that encode ion channels, such as the Na+ channel (SCN5A), funny current (HCN4), and Ca2+ channel = (CASQ2). • Acute inferior wall myocardial ischemia/infarction is associated with a transient alteration of neurologic rhythm control. • Heart failure has demonstrated down regulation of funny current channels. • Extreme physical conditioning can result in intrinsic changes to the SAN and the cardiac conduction system from dilation and hypertrophy (2).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Medical therapies and coexisting medical conditions should be optimized. • Device interrogation and appropriate preoperative reprogramming should be performed. • The anesthetic plan should aim for hemodynamic stability, rate control, and adequate ventricular filling/ejection. • Preoperative therapeutic anticoagulation must be optimized. Chronic anticoagulation is recommended in tachy-brady syndrome and chronic atrial fibrillation. Preoperative therapeutic anticoagulation must be optimized.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Syncope, dizziness, or lightheadedness • Palpitations

• Fatigue, poor exercise tolerance • Dyspnea, orthopnea

History

• History of dysfunction and type • Coexisting conditions and risk factors – CAD is common • Functional status

Signs/Physical Exam

• CV exam – Irregular rhythm on auscultation or palpation of pulses, bradycardia/tachycardia, JVD, orthostatic hypotension – Carotid massage: A sinus pause >3 seconds should elicit concern for SSS. – A Valsalva maneuver will not cause an increase in the HR (3) • Extremities – Cyanosis: Thromboembolism – Edema from congestive heart failure • Neurologic – Focal deficits: Stroke TREATMENT HISTORY

Permanent pacemaker +/– defibrillator placement. Patients with any form of tachycardiarelated SSS may require rate control with beta-blockers and appropriate prevention of bradycardia with pacing. MEDICATIONS

• Medical treatment is utilized in accordance with specific symptoms or rhythm disturbance. – Warfarin therapy particularly in tachy-brady syndrome – Negative chronotropic medications (beta-blockers, calcium channel blockers, digitalis) may be used in select patients with a tachycardic component, but may cause excess bradycardia, block or arrest and should be used judiciously as chronic treatment. Pacemaker placement may aid with maximizing therapy. – Rhythm conversions with procainamide or quinidine are uncommon and unpredictable. – Theophylline therapy may be employed with dual-chamber pacing (1,3). DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, INR, PTT • EKG: May demonstrate pacing or a variety of manifestations in untreated patients • Cardiac enzymes in the setting of recent onset arrhythmias • Pacemaker device interrogation. The type, setting, and manufacturer of the pacemaker should always be determined. Device interrogation may be appropriate if not performed recently or there are concerns of malfunction based on the patient’s symptoms. • Preoperative consultation with cardiology/EP care team does not typically require a full

workup, provided that the patient is regularly followed in clinic.

CONCOMITANT ORGAN DYSFUNCTION

• CV (as described above) • Neurologic: Focal deficits as well as generalized CNS deficits related to cerebral hypoperfusion • GI and renal dysfunction also as a result of organ hypoperfusion

CLASSIFICATIONS

• Generally SSS is classified by the distinct rhythm and or rate disturbance that is specific to each patient’s condition. • Intrinsic versus extrinsic causes (4)

TREATMENT PREOPERATIVE PREPARATION Premedications

Implanted pacemakers allow for rate control with beta-blockers and Ca+ channel blockers in the case of tachyarrhythmias. If a pacemaker device is not present, these medications may exacerbate the underlying conduction disturbance and should be utilized cautiously. Similar disturbances may result from sympatholytic medications such as clonidine or methyldopa (1,5). Special Concerns for Informed Consent

• Delay of elective surgery in view of new or incompletely investigated arrhythmias • Thromboembolic or hemorrhagic complications • Possible need for intraoperative cardioversion and/or pacing.

INTRAOPERATIVE CARE Choice of Anesthesia

• Dictated by the procedure and comorbidities, with consideration given to sympatholytic activity or effect that may uncover or worsen bradycardias. • Regional and neuraxial methods may be contraindicated in the setting of anticoagulation therapy. – Neuraxial techniques may blunt the cardioaccelerator fibers (T1–T4). Monitors

• Standard ASA monitors with EKG • Noninvasive BP monitor may be acceptable in hemodynamically stable patients, but the threshold for arterial catheter placement should be lowered. • Central venous line and transesophageal echocardiography may also be considered

Induction/Airway Management

• No specific induction agents/methods have been established. The sympatholytic effects of

induction agents can produce transient or sustained bradyarrhythmias (5). • IV lidocaine administration may interrupt sinus node activity causing arrest or severe bradycardia (6) • Sympathetic discharge associated with laryngoscopy may elicit tachyarrhythmias in patients with tachycardia related SSS (5). • In asymptomatic patients, SSS may be unmasked and require halting the procedure pending workup.

Maintenance

• General anesthesia with either IV or inhalational administration may be acceptable. • New onset bradycardia may initially be treated with beta-agonists or antimuscarinics.

Extubation/Emergence

• Minimize sympathetic simulation • Balanced titration of reversal agents

FOLLOW-UP BED ACUITY

• Routine postoperative care in hemodynamically stable patients with uncomplicated course • Step down or ICU bed for any hemodynamic instability or new onset sinus node dysfunction

MEDICATIONS/LAB STUDIES/CONSULTS

• Anticoagulation as indicated, beta or calcium channel blocker for control of tachyarrhythmias • Electrolytes, cardiac enzymes where indicated by new onset sinus dysfunction • Device reprogramming, cardiology/EP follow-up

COMPLICATIONS

• Myocardial ischemia • Cardiac arrhythmias • Systemic hypoperfusion/ischemia • Thromboembolism versus bleeding

REFERENCES

1. Adan V, et al. Diagnosis and treatment of sick sinus syndrome. Am Fam Physician. 2003;67:1725–1732. 2. Monfredi O, et al. The anatomy and physiology of the sinoatrial node-a contemporary review. Pacing Clin Electrophysiol. 2010;33(11):1392–1440. 3. Brignole M. Sick sinus syndrome. J Clin Geriatr Med. 2002;18:211–227. 4. Epstein AE, et al. ACC/AHA/HRS 2008 Guidelines for device-based therapy of cardiac rhythm abnormalities: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation.

2008;117(21):2820–2840. 5. Atlee JL. Perioperative cardiac dysrhythmias. Anesthesiology. 1997;86(6):1397–1424.

6. Kim KO, et al. Profound bradycardia with lidocaine during anesthesia induction in a silent sick sinus syndrome patient. J Clin Anesth. 2011;23(3):227–230.

ADDITIONAL READING

• Bradycardia • Pacemaker cells in the heart • Pacemaker dependent

CODES ICD9 427.81 Sinoatrial node dysfunction ICD10 I49.5 Sick sinus syndrome

CLINICAL PEARLS

• Patients with signs/symptoms attributable to SSS but without appropriate out-patient follow-up should receive a complete preoperative workup for elective procedures. • Temporary pacing may be required in patients with suspected or diagnosed SSS who do not have implanted pacemakers. • Sympatholytic therapies, vagal stimulation associated with induction, intubation and surgical procedures may uncover SAN dysfunction. • New onset sinus abnormalities and/or arrhythmias should prompt postponement of nonemergent procedures. • Asymptomatic sinus bradycardia in older patients may be the only preoperative sign of SAN dysfunction.

SICKLE CELL DISEASE Radha Arunkumar, MD

BASICS DESCRIPTION

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by chronic hemolysis, acute painful vaso-occlusive crises, and end-organ damage EPIDEMIOLOGY Prevalence

• Most common in people of African and Mediterranean descent; also common in people from the Caribbean, South and Central America, Middle East, and parts of India • Greater than 230,000 affected children are born every year in sub-Saharan Africa. • In North America and Europe, ∼2,600 and 1,300 affected children are born every year, respectively (1).

Prevalence

• Prevalence of SCD is highest in sub-Saharan Africa. • Affects 50,000–100,000 people in the US. • 1 in every 600 African-Americans has SCD.

Morbidity

• Approximately 30% of patients have severe disease with widespread organ damage and early death, 60% have a less devastating clinical course, and 10% remain relatively well most of their life. • Risk factors for increased perioperative morbidity include increased age, pregnancy, and preexisting infections. Mortality

• In the US, the mean age at death for men and women with SCD is 42 and 48 years, respectively • Organ failure is a significant cause of perioperative mortality

ETIOLOGY/RISK FACTORS

• Hemoglobin A (HbA) is the predominant hemoglobin in adulthood; it has 2α and 2β globin chains. A single point mutation in the 6th codon on the α globin chain results in substitution of valine for glutamic acid and hemoglobin S (Sickle Hb – molecular hallmark of SCD). This defect creates a new hydrophobic spot on the outer portion of the molecule (normally hydrophilic and in contact with plasma) (2). • In both normal and sickle Hb, deoxygenated Hb results in a small hydrophobic patch; thus in SCD, there is a double hydrophobic spot that seeks out and sticks to other hydrophobic

spots on other Hb molecules. As a result, deoxygenated Hb aggregates into chains; the tetramers stick to each other and polymerize (form long fibers) instead of remaining independent. • Risk factors that favor “sickling” – Hb deoxygenation secondary to hypoventilation and hypoxemia – Decreased perfusion secondary to decreased cardiac output, hypotension, hypovolemia/dehydration, and cardiopulmonary bypass – Venous stasis secondary to patient immobility, extremity tourniquets, and improper patient positioning – Metabolic factors such as acidosis, hypothermia, and infection – Alcohol binges, high altitudes, and prolonged airline flights also precipitate complications in SCD patients.

PHYSIOLOGY/PATHOPHYSIOLOGY

• “Sickling” results in the normally pliable biconcave erythrocyte assuming a rigid sickle shape on deoxygenation. This causes cell membrane damage, hemolysis, clogging of the microcirculation, and ischemic organ damage with vaso-occlusive crises. • Vaso-occlusive processes account for the majority of complications; clinical presentation depends on the vascular bed affected • Increased hemolysis – Decreases the red blood cell lifespan from ∼120 days to ∼15 days, resulting in anemia. – Disrupts intracellular nitric oxide (NO) metabolism and hence decreases NO bioavailability. This causes increased endothelial oxidant and shear stress with resultant endothelial inflammation and exacerbation of vasoconstriction and tissue ischemia (3). • Oxyhemoglobin curve is shifted to the right (P50 = 31 mm Hg, compared to normal P50 = 27 mm Hg). This reflects the decreased affinity of Hb for oxygen.

Pregnancy Considerations

Painful crises occur more commonly during pregnancy ANESTHETIC GOALS/GUIDING PRINCIPLES

• Pathophysiological changes that accompany SCD may necessitate a surgical procedure such as splenectomy, cholecystectomy, skin grafting for leg ulcers, curettage of osteomyelitic bone cavities, acute abdomen, orthopedic prosthetic surgery, Cesarean section, etc. • Since reversal of the sickling process is difficult, the focus is on prevention. Thus, goals for perioperative care include avoidance of acidosis, hypoxemia, dehydration, venous stasis, and hypothermia. • Patients may have increased narcotic requirements from chronic use.

PREOPERATIVE ASSESSMENT SYMPTOMS • Pain • Fever

• Dyspnea, tachypnea

History

• SCD should be considered in patients of African-American descent. • Exacerbations and hospitalizations • Evidence of chronic organ damage including lung, kidney, liver, spleen, and brain

Signs/Physical Exam

• Vital signs including room air saturation and pain score • Dactylitis is inflammation of an entire digit that can result from a vaso-occlusive crisis with bone infarcts; it is a hallmark of severity of SCD. • Cardiac assessment • Respiratory evaluation for obstructive and restrictive lung disease • Neurologic assessment

TREATMENT HISTORY

• Bone marrow transplant • Exchange transfusions are used to alter the Hb level rapidly and to replace sickle cells with normal cells. Thus, it reduces the concentration of sickle cells without increasing the hematocrit, whole blood viscosity, or iron accumulation (the volume of HbA containing cells infused is equal to what is removed). However, outcomes studies have not supported its use. • Blood transfusions to maintain a hematocrit greater than 30%. The efficacy of this has not been demonstrated in a randomized trial. The Transfusion Alternatives Preoperatively in Sickle cell disease (TAPS) is a randomized controlled trial that is currently being undertaken to compare outcomes with and without transfusion (4).

MEDICATIONS

• Hydroxyurea increases Hb F production and has been shown to decrease pain episodes, acute chest syndrome (ACS) events, and hospitalizations (5)[A]. • Folate • Narcotics • ACE inhibitors

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Sickledex test –screening for SCD – addition of reducing substance to peripheral blood smear under microscope to demonstrate sickling • Hb electrophoresis – More specific test to demonstrate HbS% • Evaluation for end-organ damage – CBC, coagulation studies – Anemia – Renal function tests – BUN, creatinine, urinalysis for proteinuria, and occult infection – Liver function tests and bilirubin levels – EKG – CXR, ABG, lung function tests

• Immediate preoperative Hb within 24 hours, since it may change rapidly. • Blood type and screen to rule out alloantibodies from frequent transfusions.

CONCOMITANT ORGAN DYSFUNCTION

• Central nervous system: Overt stroke is seen in up to 11% of patients before the 3rd decade of life. Ischemic stroke is more common in the 1st decade, while hemorrhagic stroke occurs more frequently in the 3rd decade. Risk factors for stroke include low Hb levels, elevated leukocyte counts, elevated homocysteine levels, low HbF%, hypertension, or recent or frequent ACS. Cognitive impairment from ischemic brain lesions can occur in the absence of clinically overt stroke. • Cardiovascular system: Anemia is compensated with a hyperdynamic circulation, expanded plasma volume, and dilated cardiomyopathy at an early age. • ACS: Caused by sequestration of sickled cells, fat embolism, and thrombosis in the pulmonary vasculature. Frequent cause of hospitalization and leading cause of death. May present as dyspnea, tachypnea, wheezing, fever, pleuritic pain, or a drop in Hb level. CXR may reveal a new pulmonary infiltrate. • Pulmonary: Chronic sickle lung disease is characterized by obstructive and restrictive lung disease, dyspnea, pulmonary hypertension, and cor pulmonale • Liver: Chronic hemolysis results in unconjugated hyperbilirubinemia that can manifest as jaundice and pigmented gallstones. • Abdominal crisis will require that the clinician rule out an acute abdomen. • Skeletal system: Microvascular occlusion of bone marrow results in severe pain in the back, femur, ribs and sternum, necessitating treatment with opioid analgesics. Can result in dactylitis (early onset in severe disease) or Salmonella osteomyelitis. • Renal: Dysfunction due to vaso-occlusion causing hematuria, decreased urine concentrating capacity, glomerular injury, progressive proteinuria • Spleen: Acute splenic sequestration of blood with life-threatening anemia, painful massive splenomegaly, and cardiovascular collapse can occur. Over time, splenic atrophy can result with the loss of splenic function due to vaso-occlusive autoinfarction; patients are more susceptible to overwhelming bacterial infections that can be fatal. • Skin: Painful ulcerations around the ankles are very common. • Painful crisis is the most common reason for hospitalization; results from ischemia and infarction precipitated by vaso-occlusion • Other: Priapism, avascular necrosis of the femoral head, retinopathy, vitreous hemorrhage and hyphema with sudden blindness, hearing loss.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Dehydration should be corrected • Preoperative prophylactic transfusion to a HCT goal of 30% is of potential benefit in moderate and high-risk cases. • Exchange transfusions may be considered prior to major surgery.

CLASSIFICATIONS

• Homozygous (HbSS): Trait is inherited from both parents • Heterozygous (HbAS): Trait is inherited from one parent and HbA from the other parent;

sickle cell trait (SCT) patient is a carrier and will not exhibit the manifestations of SCD.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytic and pain medications as appropriate • Shorter fasting times for pediatric patients

Special Concerns for Informed Consent

• Possibility of perioperative sickling and crises • Blood transfusions

INTRAOPERATIVE CARE Choice of Anesthesia

• General and regional anesthetics have both been used successfully. • Neuraxial blocks. Vasodilation and improved pain control may be beneficial. Prophylactic IV fluids should be administered to avoid hypotension.

Monitors

• Standard ASA monitors • Foley catheter may be needed to improve fluid management and resuscitation • Invasive monitoring as dictated by the surgical procedure or patient’s disease

Induction/Airway Management

• Standard induction with drugs titrated to avoid hypotension • Airway management as appropriate

Maintenance

• Oxygenation: Increased FiO2 and positive end-expiratory pressure may be necessary

• Perfusion: Fluid hydration, β agonists, or anticholinergics • Transfusion should be based on an individualized assessment of surgical circumstances and patient’s oxygen delivery. • Normothermia should be fastidiously maintained; warm intravenous fluids, apply convective warming devices, and consider warming the room. • Meticulous positioning is essential.

Extubation/Emergence

Decision is based on surgical circumstances and concomitant preexisting complications.

FOLLOW-UP BED ACUITY

ICU admission for patients with severe disease and undergoing major procedures MEDICATIONS/LAB STUDIES/CONSULTS

• Supplemental oxygen in the PACU and floor may avoid hypoxemia • Hydrate with IV fluids • Adequate treatment of postoperative pain with narcotics and/or regional blocks • Ketorolac may be given (caution in patients with severe pulmonary and renal dysfunction) • Antiemetics for PONV to avoid dehydration • Acute pain service consult for pain crisis may be warranted

COMPLICATIONS

• Atelectasis – Chest physiotherapy and pulmonary toilet in the PACU and postoperatively • Pain crisis: Pain scoring, effective analgesia with opiates, adjuvant analgesics with nonsteroidals and acetaminophen, possible regional, pulmonary monitoring, psychological support • ACS: Oxygen, effective analgesia, incentive spirometry, antibiotics, transfusion, mechanical ventilation if respiratory failure, steroids and NO may be of possible benefit.

REFERENCES

1. Rees DC, Williams TN, Gladwin MT. Sickle cell disease. Lancet. 2010;376:2018–2031. 2. Schnog JB, Duit AJ, Muskiet FAJ, et al. Sickle cell disease; a general overview. Neth J Med. 2004;62:364–374. 3. Firth PG, Head CA. Sickle cell disease and anesthesia. Anesthesiology. 2004;101:766–785. 4. TAPS RCT http://clinicaltrials.gov/ct2/show/NCT00512577 5. Brawley OW, Cornelius LJ, Edwards LR, et al. NIH Consensus Development Conference statement: Hydroxyurea treatment for sickle cell disease. Ann Inter Med. 2008;148(12):932–938. See Also (Topic, Algorithm, Electronic Media Element) • Hypothermia • Hemoglobin

CODES ICD9 282.61 Hb-SS disease without crisis ICD10 D57.1 Sickle-cell disease without crisis

CLINICAL PEARLS

• Goals for perioperative management include avoidance of hypoxia, acidosis, dehydration,

hypothermia, and venous stasis, as well as providing adequate pain control.

SMOKE INHALATION INJURY Charles E. Cowles, Jr., MD

BASICS DESCRIPTION

• Smoke inhalation can result in – Injury to the airway due to superheated air, steam, or particulate matter – Systemic toxicities from by-products of combustion • Patients can present to the anaesthetist for initial airway management, surgery for burns and other injuries, as well as pain management. Additionally, smoke inhalation injury can result from operating room or airway fires. EPIDEMIOLOGY Prevalence

• Found in 5–35% of patients with burn injuries. • In the US, there are 700,000 burn injuries per year (1).

Mortality

• Thermal burn injury (all-cause mortality): 25–65% • Smoke inhalation injury accounts for the majority of fire-related deaths.

ETIOLOGY/RISK FACTORS

• Closed space fire • Gas, electrical, chemical, steam, or scalding injuries.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Smoke inhalation injury describes thermal injury to the airways, particulate irritation, and gaseous-related injury. – Presentation involves significant airway swelling and edema; and may be delayed – Animal models suggest that calcitonin gene-related peptide (CGRP) plays a role in increasing airway hyperemia, transvascular fluid flux, and respiratory malfunction. Attenuation with an antagonist was shown to decrease edema and alveolar inflammation. Future efforts may target this gene. – Interleukin-8 (IL-8) also appears to play a role in the inflammatory pathogenesis. In animal models, pretreatment with anti-IL-8 demonstrated attenuation of lung permeability, suggesting another potential therapeutic target. – Inducible nitric oxide synthase (NOS) also increases the effects of smoke inhalation injury; inhibition of NOS has been shown to improve pulmonary gas exchange and reduce pulmonary shunt fraction compared to controls. • Particulate irritation to the airways can be seen with gas or flame burns. The pathogenesis involves impaired motility of respiratory cilia. Additionally, it may also dissolve into

harmful substances. • Gaseous-related Injury – Carbon monoxide (CO) is a product of incomplete combustion that binds to ferric atoms in hemoglobin to form carboxyhemoglobin. CO has a 260–300 times greater affinity to hemoglobin compared to oxygen; thus it “displaces” oxygen and prevents binding and impairs oxygen delivery to tissues. As a result, tissues resort to anaerobic metabolism with resultant lactic acid production. – Hydrogen cyanide is a by-product of burning synthetic polymer materials. Cyanide binds to ferric ions in the mitochondrial electron transport chain; it prevents the final electron transfer to oxygen and halts adenosine triphosphate (ATP) production. Tissues resort to anaerobic metabolism, with resultant lactic acid production. – Acrolein results from burning wood and petroleum products and causes protein denaturation along the airways. – Hydrochloric acid is formed from burning plastics and polyvinylchloride (PVC); it can cause pulmonary edema and lethal arrhythmias. – Toluene diisocyanate is produced from burning foam products, furniture, and insulating materials; it causes severe bronchospasm upon exposure to lower airways.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintain a high index of suspicion for smoke inhalation injury based on history and physical exam. There should be a low threshold for securing the airway if thermal injury to the airways is suspected or present. Similarly, CO or cyanide toxicity, if suspected, should be confirmed and treated. • In the event of an operating room fire, or rescue scene, make sure as a healthcare provider, you do not become a victim. Evacuate yourself and the patient from the area of smoke or fumes before initiating any care.

PREOPERATIVE ASSESSMENT SYMPTOMS

Coughing, nausea, headache, confusion, somnolence History

• Type of fire • Duration of exposure • Events leading to exposure • Determine whether the fire was in an enclosed structure such as a building or vehicle

Signs/Physical Exam

• Facial burns, carbonaceous sputum, soot in the mouth, singeing of facial hair, and second or third degree burns elsewhere on the body correlate strongly with associated airway injuries (2). • “Cherry Red” colored skin and mucosal surfaces are very late findings and are often noted post-mortem.

TREATMENT HISTORY

• Intubation if airway edema is suspected • High-frequency oscillatory ventilation (HFOV) has been shown to significantly improve oxygenation in burn injury patients, but not in patients with smoke inhalation injury (3)[A]. • High concentrations of oxygen are required for the treatment of CO toxicity as a bridge therapy until hyperbaric treatment can be provided. Hyperbaric oxygen therapy is the delivery of 100% oxygen at increased atmospheric pressures. By providing an overabundance of oxygen, CO is displaced from hemoglobin molecules. MEDICATIONS

Hydroxocobalamin for cyanide toxicity; the cyanide antidote kit should be avoided because nitrites can result in a methemoglobinemia that could be fatal if the patient also has high levels of carboxyhemoglobin. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Arterial blood gas (ABG) with carboxyhemoglobin level • Electrocardiogram (EKG) • Lactate levels (4)

CONCOMITANT ORGAN DYSFUNCTION

• Acute respiratory failure from burn injury • Acute renal failure from rhabdomyolysis • Severe fluid redistribution in burn patients

CIRCUMSTANCES TO DELAY/CONDITIONS

• Due to significant associated morbidity and mortality, only emergency surgery should be contemplated in the patient with suspected smoke inhalation. • Carboxyhemoglobin levels >25% should be strongly considered for hyperbaric oxygen therapy prior to any operative procedure.

TREATMENT PREOPERATIVE PREPARATION Premedications

Benzodiazepines and opioids can cause respiratory depression or affect hemodynamics; if administered, should be done judiciously and with monitoring. Special Concerns for Informed Consent

Attempts to obtain consent should be made, as with any emergency case. However, it should not delay life-saving treatment INTRAOPERATIVE CARE

Choice of Anesthesia

• General endotracheal anesthesia is commonly chosen due to the emergent nature of cases involving smoke inhalation and the need for a secured airway. Thus, regional and neuraxial blocks as a sole anesthetic are not appropriate. • Regional anesthesia such as nerve blocks and epidural anesthesia can be considered for management of pain, but factors such as the patient’s ability to communicate, urgency of the procedure, and hemodynamic stability should be strongly considered.

Monitors

• Standard ASA monitors • Arterial line for frequent blood gas measures and assessment of the pH • Co-oximetry for detection of CO. The standard pulse oximeter and ABG are not capable of distinguishing between carboxyhemoglobin and oxyhemoglobin (can yield falsely elevated oxygen levels).

Induction/Airway Management

• If a difficult airway is anticipated, have a fiberoptic bronchoscope, indirect video laryngoscope (Glidescope), jet ventilator, or surgical airway available. Consider utilizing advanced techniques during the initial attempt. • Smaller endotracheal tubes should be available; if burns affect the lips or nose, use of an extended length, small diameter tube may be considered to accommodate swelling. • Patients are considered to have a “full stomach” for recent burns; however, rapid sequence inductions are contraindicated if a difficult airway is suspected. Consideration may need to be made for an awake fiberoptic intubation. • Succinylcholine should be avoided if the burn injury occurred >24 hours. The proliferation of extrajunctional receptors can result in profound hyperkalemia. • Etomidate is capable of maintaining good hemodynamic stability, but is associated with adrenal insufficiency. This may be of concern if multiple surgeries are anticipated

Maintenance

• Volatile agents may result in further airway irritability and may even have impaired uptake and elimination with severe lung injury. • Fluid management should be guided by the associated burn injury and the time interval since the burn injury. Patients who have developed lung injury are particularly susceptible to pulmonary edema from excess fluid administration. • Hypothermia can be an issue for all burn patients, and is exacerbated by the vasodilatory effects of general anesthetics. Prevention of heat loss, the use of forced air warming blankets, and increasing the ambient room temperature of the operating room may help prevent hypothermia.

Extubation/Emergence

Use caution if recent burn injury to airways, as swelling may worsen during the first 24 hours. Consider leaving the patient intubated postoperatively with appropriate sedation.

FOLLOW-UP BED ACUITY

Burn unit is the most suitable location

MEDICATIONS/LAB STUDIES/CONSULTS

• Patient should be managed by a burn specialist and intensivist who is capable of managing difficult airways and performing repeat bronchoscopies. • Serial lactate and carboxyhemoglobin can aid with directing therapy in CO and cyanide toxicity.

COMPLICATIONS

• Smoke inhalation may be an overlooked problem in patients with other trauma or with distracting burn injuries. • Hypoxemia is possible from progressive lung injury and systemic toxicities. • Significant airway edema can occur in the first 24 hours after exposure, even if the initial presentation appears unremarkable.

REFERENCES

1. all JR.Burns, Toxic Gases, and Other Hazards Associated with Fires: Deaths and Injuries in Fire and Non-Fire Situations. Quincy, MA:. National Fire Protection Association, Fire Analysis and Research Division, 2001. 2. Madnani DD, Steele NP, de Vries E. Factors that predict the need for intubation in patients with smoke inhalation injury. Ear Nose Throat J. 2006;85(4):278–280. 3. Cartotto R, Walia G, Ellis S, et al. Oscillation after inhalation: High frequency oscillatory ventilation in burn patients with the acute respiratory distress syndrome and co-existing smoke inhalation injury. J Burn Care Res. 2009;30:199–227. 4. Baud F, et al. Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med. 1991;325:1761–1766.

ADDITIONAL READING

• Center for Disease Control. http://www.cdc.gov/HomeandRecreationalSafety/FirePrevention/fireactivities.htm • Undersea & Hyperbaric Medical Society. www.uhms.org See Also (Topic, Algorithm, Electronic Media Element) • Burns • Carbon monoxide poisoning • Cyanide toxicity • Hyperbaric oxygen therapy • Ciliary function

CODES ICD9

987.9 Toxic effect of unspecified gas, fume, or vapor ICD10 T59.814A Toxic effect of smoke, undetermined, initial encounter

CLINICAL PEARLS

• Early endotracheal intubation should be undertaken if airway burns are suspected, even if the burn injury appears minor. • Assess for carboxyhemoglobin levels; standard pulse oximetry is not capable of distinguishing between carboxyhemoglobin and oxyhemoglobin. Early hyperbaric oxygen therapy is beneficial for CO poisoning. • Consider cyanide toxicity for cases involving closed spaces or structural fire, which is treated with hydroxocobalamin and not a standard cyanide kit.

SMOKING

Jagan Devarajan, MD, FRCA Beth H. Minzter, MD, MS, FIPP

BASICS DESCRIPTION

• Anaesthetists commonly encounter patients with both short and long term sequelae of smoking and its associated pulmonary and cardiovascular complications in the perioperative period. • An upcoming surgery can provide an opportunity and motivation to quit smoking for ever, as patients are forced to abstain due to non-smoking policies that are practiced by hospitals. Thus, if possible, anaesthetists should play a role in counseling preoperatively, and as healthcare providers, have a responsibility to advise for permanent cessation. EPIDEMIOLOGY Prevalence

• Approximately 1 in 5 adult Americans currently smoke. • Higher in men (23.9%) than women (18%)

Morbidity

Smoking has adverse effects on every organ system in the body and reduces health in general. It impairs physical fitness, endurance, and general well-being. Mortality

Approximately 1 in every 5 deaths each year (443,000 deaths) is attributed to either direct or indirect effects of smoking. More deaths are caused by smoking than that of HIV, illegal drug use, alcohol behavior, and motor vehicle accidents combined. ETIOLOGY/RISK FACTORS

• Smoke from tobacco has more than 25 carcinogens, though the most damaging products are nicotine, tar, and carbon monoxide. The particulate phase contains at least 3,500 compounds, mostly carcinogens and free radicals. • Tobacco has nicotine (2–5%), sugars (mainly reduced) (8–25%), and moisture (10–14%).

PHYSIOLOGY/PATHOPHYSIOLOGY

Nicotine stimulates preganglionic autonomic receptors, resulting in the release of epinephrine from adrenal glands, norepinephrine from nerve endings, and dopamine and endorphins from the central nervous system. They are responsible for different perceptions and behaviors, including the euphoria associated with smoking. Hence, it is a highly addictive substance. ANESTHETIC GOALS/GUIDING PRINCIPLES

Smoking cessation: Ideally smoking should be stopped 8 weeks prior to surgery (patients should be advised at the surgeon’s office or at the time of scheduling). If that does not occur or the patient is unable to stop, abstinence should be recommended for at least 24 hours prior to surgery, or the evening before surgery to decrease the deleterious effects of nicotine and carbon monoxide.

PREOPERATIVE ASSESSMENT SYMPTOMS

COPD and cardiovascular symptomatology should be sought. History

• Pack year history • Respiratory: Infections, recent COPD exacerbations, dyspnea, increased fatigability. • Cardiovascular: Evidence of coronary artery disease (CAD) (e.g., previous MI and chest pain) and peripheral vascular disease (e.g., claudication and rest pain).

Signs/Physical Exam

Respiratory and cardiovascular symptomatology should be sought. TREATMENT HISTORY Counseling

MEDICATIONS

• Nicotine replacement therapy • Bupropion, an atypical antidepressant

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Pulmonary function tests (PFTs) would demonstrate an obstructive pattern (decrease in FEV1 that is greater than the decrease in FVC, and a decreased FEV1/FVC ratio). • Arterial blood gas can show hypoxia, hypercapnia • Co-oximetry can measure carbon monoxide levels

CONCOMITANT ORGAN DYSFUNCTION

• Pulmonary system: Most common cause of lung carcinoma and COPD. Perioperatively, smoking increases airway irritability, sensitizes the reflex responses to chemical irritants, and increases mucus production. Bronchial mucus transport during general anesthesia is further slowed in smokers compared with nonsmokers. Carbon monoxide decreases oxygen binding to hemoglobin and thus decreases overall blood oxygen content. Smoking is associated with increased incidences of periopera- tive laryngospasm, bronchospasm, episodes of desaturation, development of pneumonia, respiratory failure and unanticipated ICU admission and requirement of ventilatory support. • Cardiovascular system. Increases the risk of developing CAD, cerebrovascular disease, and

stroke by 2–4 times. By accelerating atherosclerosis, it indirectly contributes to perioperative cardiac morbidity and mortality. Carbon monoxide present in smoke can injure myocardium due to chronic exposure and increases the myocardium’s susceptibility to viral infections, cardiomyopathy, and CHF. Perioperatively, smoking increases heart rate, BP, and myocardial contractility, thereby increasing myocardial work and oxygen consumption. It also increases plasma levels of catecholamines. • Hepatic system. Induces the liver microsomal enzymes; thus, medications that undergo hepatic metabolism may require increased dosing (e.g., benzodiazepines and morphine) • Endocrine system: Increases secretion of antidiuretic hormone resulting in dilutional hyponatremia • Hematologic system: Associated with increase in production of hemoglobin, RBCs, WBCs, platelets, and fibrinogen. Despite an increased incidence of thromboembolic disease in smokers, the relative risk of deep venous thrombosis (DVT) is not higher than that of nonsmokers. • Wound and bone healing. Impairs immune response. Smokers are more likely to develop postoperative complications related to wound healing such as dehiscence and infection. It also has been shown to contribute to impairment of bone healing and nonunion of spinal fusions. In patients undergoing knee and hip replacements, smoking cessation decreased wound infection from 23% to 4%. • Mutagenicity. Increases the risk of developing cancer of the lung, oral cavity, kidney, urinary bladder, cervix, stomach, and uterus. • Maternal/fetal heath. Increases the risk of infertility, abortions, ectopic pregnancy, premature rupture of membranes, and placenta previa and abruption. The risk of prematurity and low birth weight, still birth, and sudden infant death syndrome is higher in children born to smoking mothers compared to nonsmokers

CIRCUMSTANCES TO DELAY/CONDITIONS Acute COPD exacerbation

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytic medications can reduce the psychological effects of smoking cessation. • Bronchodilators in patients who show a reversible bronchospastic component to their reactive airway disease. • Antibiotics in those who have active respiratory tract infections. • Pulmonary toilet. Humidification and chest physical therapy to improve secretion clearance; incentive spirometry education. • Steroids may be considered in patients with moderate-to-severe reversible airway disease; however, their effects are not immediate and need to be weighed against potential risks.

Special Concerns for Informed Consent

Postoperative pulmonary complications such as respiratory failure, unanticipated intensive

care admission, pneumonia, laryngospasm, bronchospasm, and increased requirement of postoperative respiratory therapy and aerosol therapy INTRAOPERATIVE CARE Choice of Anesthesia

• Local or regional anesthesia are often preferable to general anesthesia (avoids airway manipulation, positive pressure ventilation, and unpredictable interactions with opioids). • Neuraxial techniques for surgical anesthesia. Motor blockade above the T10 level can markedly decrease the forced expiratory flow in patients with impaired pulmonary function. • Epidural analgesia for postoperative pain can facilitate deep breathing and coughing and improves respiratory care.

Monitors

• Pulse oximetry: Beware of overestimation of oxygen saturation due to the presence of carboxyhemoglobin. May require pulse oximetry with multiple wavelengths to attain accurate readings. • Electrocardiogram with ST segment analysis can help detect myocardial ischemia. • Arterial line. In major surgeries, especially neurosurgical cases, paCO2 measurements are highly recommended to estimate the paCO2 – EtCO2 gradient (smokers have elevated

gradients).

Induction/Airway Management

• Preoxygenation (denitrogenation) with 100% oxygen can negate the effects of increased closing capacity and carbon monoxide levels. • Any IV induction agent at adequate dosages is satisfactory. Although thiopental does not cause bronchospasm, it does not blunt reactivity. • IV lidocaine is useful during induction to decrease airway reactivity to intubation, or, alternatively, one can spray lidocaine on the vocal cords before intubation. • Airway manipulation and surgical stimulation should be avoided during the “excitatory stages” of anesthesia to decrease the incidence of respiratory-related adverse events.

Maintenance

• Volatile agents are preferred due to their salutary effects on bronchial reactivity. Avoid introduction of high concentrations of desflurane during induction to prevent breathholding and laryngospasm. Desflurane stimulates respiratory irritant receptors in chronic smokers and thereby the sympathoadrenal system, resulting in higher BPs and tachycardia. Nitrous oxide is not contraindicated in patients without bullous emphysema; however, underlying respiratory pathology may decrease the patient’s ability to tolerate decreased FiO2.

• Neuromuscular blockade. If utilized, neuromuscular monitoring is mandatory for the titration of muscle relaxants. Nicotine stimulates nicotinic acetyl cholinergic receptors in small plasma concentrations resulting in increased requirement of muscle relaxants to induce and maintain neuromuscular blockade. This effect, however, is not uniform among all muscle relaxants. Monitoring will help to prevent bucking and bronchospasm during maintenance.

Extubation/Emergence

• Extubation in the excitatory stage of anesthesia can result in laryngospasm, bronchospasm, and breath holding. Consider a “deep extubation,” if appropriate. • Nicotine may have antinociceptive effects and decrease the incidence of nausea and vomiting. However, prophylactic antiemetics should still be considered.

FOLLOW-UP BED ACUITY

Dependent on surgical procedure, intraoperative events, and the need for postoperative intubation and mechanical ventilation MEDICATIONS/LAB STUDIES/CONSULTS

• Oxygen therapy usually will be required in the PACU and occasionally on the nursing floor. • Requirement of analgesics often will be higher due to increased metabolism of drugs and decreased pain threshold. Patient-controlled analgesia (PCA) is highly recommended. Regional, epidural, and field blocks should be considered, if appropriate. • Breathing exercises, physical therapy, and incentive spirometry are mandatory. • DVT prophylaxis • Surveillance of wounds to facilitate early detection and treatment of wound infections • Nicotine patches may be prescribed to prevent nicotine withdrawal. Nicotine patches are not known to increase wound infections.

COMPLICATIONS

Nicotine withdrawal, inadequate pain control, poor wound healing, DVT, PPC

REFERENCES

1. CDC. Cigarette smoking among adults – United States, 2006. MMWR. 2007;56:1157–1161. 2. Turan A, Mascha EJ, Roberman D, et al. Smoking and perioperative outcomes. Anesthesiology. 2011. 3. Warner DO. Perioperative abstinence from cigarettes: Physiologic and clinical consequences. Anesthesiology. 2006;104:356–667. See Also (Topic, Algorithm, Electronic Media Element)

• Chronic bronchitis • Oxygen-carrying capacity

CODES ICD9 305.1 Tobacco use disorder

ICD10

Z72.0 Tobacco use

CLINICAL PEARLS

• All hospitals are nonsmoking, forcing patients to adopt a nonsmoking behavior, which will give them the chance to experience the effects of abstinence from smoking and to explore options for continued cessation in the future. • Anaesthetists should follow the simple three-step system approach designed by the ASA Smoking Cessation Initiative Task Force: – A – Ask a patient about smoking status – A – Advise smokers to quit, and – R – Refer smokers to free national telephone quit line • Anaesthetists should also advise and help smokers to stop smoking during the postoperative ward rounds. Patients who develop smoking-related complications are shown to be compliant with the postoperative instructions. • Pulmonary effects of smoking cessation. Ciliary function improves in 48–72 hours; sputum production decreases in 1–2 weeks; pulmonary function improves after 4–6 weeks; and the immune function of alveolar macrophages improves in 6–8 weeks. The incidence of PPC was not different between patients who continued to smoke until surgery (48%) and those who quit within 8 weeks before surgery (56%). In contrast, those who quit >8 weeks before surgery (17%) had a rate of PPCs similar to that of nonsmokers (11%). • Cardiovascular effects of smoking cessation. Even a short period of abstinence should have beneficial effects on the cardiovascular system, as the major culprits such as nicotine and carbon monoxide have short elimination half lives (1 and 4 hours, respectively). At 8 hours, BP and heart rate decrease. As CO levels return to normal in 12–24 hours, O2 levels and body temperature increase to normal. At 24 hours, the risk of acute coronary event decreases. By 1 year, there is a 50% reduction in the risk of CAD. By 5 years, CVA and CAD risk is reduced to that of nonsmokers. • This cessation of smoking for 1 or 2 days can produce excessive anxiety, increased secretion of mucus, as well as a bronchospastic and hypercoagulable state. Nevertheless, these symptoms can be managed with anxiolytics, bronchodilators, and anticoagulants. By continuing not to smoke in the perioperative period, patients may benefit in the long term.

SOMATOSENSORY- AND MOTOR-EVOKED POTENTIALS (SSEP AND MEP) Carsten Nadjat-Haiem, MD

BASICS DESCRIPTION

• Evoked potentials are electrophysiologic responses of the nervous system to stimulation of either sensory or motor pathways. • Monitoring somatosensory-evoked potentials (SSEPs) and motor-evoked potentials (MEPs) can aid with assessing the integrity of the brain, brainstem, spinal cord, and peripheral nervous system during surgeries where these structures are at risk for injury. • Intraoperative changes in evoked potentials can be due to ischemia, surgical injury, and physiologic and pharmacologic influences. Physiologic factors include carbon dioxide and oxygen tension, BP, acid–base balance, hematocrit, and temperature. • To the anaesthetist, the effect of the various anesthetic agents used is of paramount importance as to assure proper anesthetic depth and hemodynamics in addition to gaining proper monitoring conditions. PHYSIOLOGY PRINCIPLES

• SSEP monitoring was first adopted in the 1980s and their advent improved neurological outcome. However, there were instances where patients would suffer from motor deficits because SSEPs do not monitor motor pathways. – Transcranial stimulation developed in the mid-1980s and allowed for integrity assessment of the motor pathway, but the initial quality of the MEPs was poor. – The introduction of high frequency multi-pulse stimulation in the early 1990s (and now post-tetanic MEPs) significantly improved recordings. • Evoked potentials are a measurement of electrical potentials in response to stimulating the nervous system via electrical, sensory, or magnetic stimulation. • SSEPs are used to assess the integrity of the sensory pathway. – Spinal cord transmission is via the posterior spinal cord and the blood supply is via a pair of posterior spinal arteries. – Generation of stimuli is typically via electrodes and electrical current being applied near peripheral nerves (e.g., median nerve, posterior tibial nerve, and peroneal nerve); the impulse travels cephaladly along the posterior cord. – Recordings of the transmitted electrical potential are made at subcortical levels (e.g., neck, spine, and epidural space) or at the cortical levels from the scalp or cerebral cortex on the contralateral side. – The potentials generated in this fashion are small compared to the EEG; therefore repetitive stimulation and summation, in addition to computer averaging, are used to gain a stable waveform. – Amplitude is the peak-to-trough voltage difference. Amplitude changes are expressed as a

percentage change from baseline recordings. – Latency is the time from stimulation to peak response. It is dependent on the location of the recording (i.e., it takes more time for the impulse to travel to a subcortical versus a cortical level). Again, the change in latency is determined by comparing baseline recordings to later recordings. • MEPs are used to test the integrity of the motor pathways. – Spinal cord transmission is via the anterior spinal cord and the blood supply is comprised of a single anterior spinal artery (arises from the vertebral arteries) that is supplemented in the caudal cord by anterior segmental medullary arteries and the artery of Adamkiewicz. – Generation of the potential occurs transcranially at the motor cortex via electrical or magnetic stimulation and travels caudally to the peripheral nerves. – Recordings take place at the spinal nerves, peripheral nerves, or distal muscle level. – Unlike SSEPs, MEPs have large interpatient variability. Changes in amplitude and latency from baseline to later recordings have little clinical relevance. Therefore, MEPs most often are recorded as being either present or absent.

ANATOMY

• SSEPs travel along the following pathway: – Peripheral stimulus – Peripheral nerve – Dorsal root ganglia – First-order fibers in the posterior column nuclei – Second-order fibers crossing to the opposite site – Medial lemniscus to the thalamus – Third-order fibers to the frontoparietal sensorimotor cortex • MEPs travel along the following pathway: – Motor cortex stimulation – Corticospinal tract – Anterior horn of spinal cord – Peripheral motor nerve

DISEASE/PATHOPHYSIOLOGY

There are many diseases and conditions affecting SSEPs and/or MEPs. They include any physical lesion along the conducting pathway; chronic renal failure, hepatic encephalopathy, hyperthyroidism, diabetes mellitus, myoclonus epilepsy, stroke, coma; Friedreich’s ataxia, Guillain–Barré syndrome, leukodystrophies, multiple sclerosis, polyneuropathy, and Reye’s syndrome. PERIOPERATIVE RELEVANCE

• SSEP monitoring. The exact criteria of what constitutes clinically relevant changes are lacking. – Latency: changes of 7–10% can occur without resultant neurological deficits. Typically an increase of 50% indicates neurological sequelae. – Decreased amplitude is considered a more sensitive indicator than increased latency.

• Volatile anesthetics and SSEPs. Inhibit synaptic transmission to a greater extent than axonal transmission. – Manifests as dose-dependent decreases in amplitude and increases in latency. In addition, they can cause morphologic changes in the waveform. – There is less effect on readings when recordings are made at the cortical level in patients with good baselines, even at one MAC (and possibly up to 1.3 MAC with sevoflurane and desflurane) in the majority of subjects, if no nitrous oxide is used. – There is a greater effect on readings when recorded further away from the generator (e.g., at the cortical rather than the spinal level). • Nitrous oxide and SSEPs: – Dose-dependent decreases in cortical amplitude with intact latency occur at concentrations of 60–70%. – Equipotent levels (in terms of MAC) depress readings greater than volatile anesthetics and most IV anesthetics. • IV anesthetics affect SSEPs to a lesser extent than volatile anesthetics. – Propofol is similar to barbiturates in terms of SSEP modulation. Even large induction doses of 2.5 mg/kg usually do not produce amplitude changes, but may increase latency up to 20%. TIVA with propofol/opioid may initially cause significant decreases in amplitude and increases in latency, but these usually return to baseline after 30 minutes. – Etomidate will actually increase cortical amplitude up to 400%, but may decrease subcortical amplitude by up to 50%. – Ketamine will also increase cortical amplitude, but has no effect on subcortical waveforms. – Barbiturates at high doses allow for SSEP recordings, but may increase latency and decrease amplitude. – Opioids at high doses have minimal effects. Overall, on an equipotent basis, a propofol/opioid technique will cause less amplitude reduction and latency increase than other techniques. – Benzodiazepines do not have a significant effect; at high doses, they can have a moderate effect at best. – Neuromuscular blocking drugs have no influence on SSEPs and may actually improve recordings by eliminating eletromyogenic artifacts. – Other drugs such as clonidine, dexmedetomidine, adenosine, and droperidol have a minimal effect on SSEPs. • Regional anesthesia diminishes or even eliminates SSEPs depending on the density of the block. • Metabolic effects on SSEPs: – Hypothermia will increase latency, but amplitude changes are variable. SSEPs are preserved at temperatures where the EEG is isoelectric. – Hypocarbia decreases latency; it has no effect on amplitude in anesthetized subjects. Mild hypercarbia has no effect. – Mild hypoxia (to a paO2 of 48 mm Hg) does not affect SSEPs. However, worsening hypoxia will decrease amplitude and increase latency. – Hypotension below the level of autoregulation will decrease amplitude without affecting

latency. – Hemodilution affects amplitude as follows: Increases at a Hct between 16% and 20% and decreases at a Hct between 11% and 15%. • MEP monitoring. The stimulus technique now employs multi-pulse stimulation in order to increase response amplitudes. In general, MEPs have a large inter- and intrapatient trial-totrial variability. Because of this large variability, no specific criteria to warn of impending injury have been established. Therefore, some will regard MEPs as either present or absent to make clinical decisions. • Volatile agents and MEPs: – Low levels can significantly affect readings. – Isoflurane can be used up to 0.5 MAC only if multi-pulse stimulation is used. – Concentrations of 0.75 and 1 MAC will yield adequate responses in only 61% and 8% of the time, respectively. – Direct stimulation of the motor cortex will allow for concentrations of up to 1.5 MAC isoflurane or sevoflurane. – Measurements at the spinal level allow for higher levels of volatile agents without an effect on readings (levels up to 1 MAC have minimal effect). • Nitrous oxide and MEPs: – Concentrations up to 50% added to agents such as opioids, ketamine, and low-dose propofol (up to 50 μg/kg/min) will not cause significant myogenic responses if multipulse stimuli are used. – Higher doses of nitrous oxide will reduce amplitudes. – Spinally recorded MEPs allow for concentrations of up to 70%. • IV agents and MEPs: – Propofol has become the first choice agent when obtaining MEPs because of its rapid metabolism, titratability, and quick emergence. There is, however, a limit beyond which propofol will depress MEPs. Infusion rates of 75–100 μg/kg/min will cause MEP depression in 33–83% of patients. Above this rate, adequate MEPs were obtained in only 60–88% of patients. This depression cannot be overcome by increasing impulse numbers per stimulation. – Etomidate is the ideal agent for MEP acquisition. Induction doses of 0.3 mg/kg will suppress MEPs for 2–5 minutes and then return to baseline. Etomidate infusions of 10–30 μg/kg/min will yield excellent MEPs. Depression of the adrenocortical axis due to etomidate infusion needs to be carefully weighed against obtaining quality MEPs. – Thiopental will cause loss of MEPs at total doses of 4–9 mg/kg. – Methohexital infusions of 100 μg/kg/min with ketamine (20 μg/kg/min) and 25% nitrous oxide will yield adequate myogenic MEPs even with single train stimulation. – Under single pulses, methohexital and etomidate infusions will yield better MEPs than propofol at equipotent doses. – Ketamine, like etomidate, is an excellent choice for obtaining MEPs. It should be strongly considered when a subject’s baseline MEPs may be marginal to begin with. – Opioid infusions have minimal effects on MEPs obtained by multi-train stimulation. Bolus doses (e.g., fentanyl) can depress MEPs for several minutes. Remifentanil is less suppressive than other opioids and may be an ideal choice.

– Benzodiazepines cause less depression than propofol or thiopental. Usual doses given as premedication pose no problems. Infusions of midazolam at 0.1 mg/kg/hr have no effect on MEPs. – Partial neuromuscular blockade to a single twitch height of 20–50% of baseline will aid with surgical exposure, if needed, while still allowing for acquisition of MEPs. Higher levels of paralysis will increase trial-to-trail variability and reduce amplitude. Less paralysis will reduce response variation. Patients with preexisting neuromuscular weakness should not be paralyzed as to avoid loss of MEPs. When using partial paralysis, twitch height has to be monitored in the same muscle groups used for MEP acquisition. • Metabolic effects on MEPs: – Clinically relevant temperatures (32–38°C) have little effect. – Deliberate hypotension to a mean BP of 60 mm Hg has little effect. – MEPs during complete ischemia of the lower limbs and the spinal cord can occur after 2 minutes if measured at the myogenic level, but take up to 30 minutes if measured as spinal potentials.

EQUATIONS

• Amplitude = Peak-to-trough voltage difference. • Latency = time from stimulus to peak response.

REFERENCES

1. Banoub M, Tetzlaff JE, Schubert A. Pharmacologic and physiologic influences affecting sensory evoked potentials. Anesthesiology. 2003;99(3):716–737. 2. Kumar A, Bhattacharya A, Makhija N. Evoked potential monitoring in anesthesia and analgesia. Anesthesia. 2000;55(3):225–241. 3. Kawaguchi M, Hayashi H, Yamamoto Y, et al. Recent advances in monitoring of myogenic motor-evoked potentials: Development of post-tetanic motor evoked potentials. J Anesth. 2008;22(4):489–492. 4. Lotto ML, Banoub M, Schubert A. Effects of anesthetic agents and physiologic changes on intraoperative motor evoked potentials. J Neurosurg Anesthesiol. 2004;16(1):32–42. 5. Sloan TB, Janik D, Jameson L. Multimodal monitoring of the central nervous system using motor-evoked potentials. Curr Opin Anesthesiol. 2008;21(5):560–564.

CLINICAL PEARLS

• Regional anesthesia diminishes or even eliminates SSEPs and MEPs depending on the density of the block. • TIVA with agents such as ketamine, etomidate, midazolam, and low infusion rates of propofol will yield the best MEPs and excellent SSEPs. • Patients who need MEP monitoring will need to have a soft bite block in place. • Close cooperation between the anaesthetist, surgeon, and electrophysiologist is needed to state monitoring goals and create a plan ahead of the procedure to obtain optimal monitoring results. • Avoid anesthetics and physiologic changes as much as possible during critical parts of an

operation (e.g., distraction during scoliosis surgery) to avoid confounding factors to the SSEPs and MEPs.

SPINAL SHOCK Laura B. Hemmer, MD Antoun Koht, MD

BASICS DESCRIPTION

• Spinal shock describes the transient loss of spinal cord function distal to a complete or incomplete acute spinal cord injury (SCI). It may last several weeks, and possibly months. • A low systemic vascular resistance (SVR) state (with hypotension) and bradycardia often coexist with acute SCI. These hemodynamic perturbations are known as neurogenic shock (a separate entity from spinal shock). • The presence of spinal shock is important in the determination of injury levels and prognosis; and it may confound the accurate assessment of neurological status in the post injury period. • In the immediate/acute post injury period, priority should be to reduce secondary injury and prevent an incomplete injury from progressing. In later months, when patients are likely to present for urological and other procedures, special attention to avoid complications of hyperreflexive responses may be required. EPIDEMIOLOGY Prevalence

In the US, the incidence of SCI is ∼12,000 cases per year (1).

Morbidity

Hypotension is associated with progression of secondary neurologic injury (1). PHYSIOLOGY/PATHOPHYSIOLOGY

• The exact definition/model of spinal shock is controversial (2). It is commonly considered to be a transient physiological interruption of spinal cord function caudal to the injury that results in areflexia, flaccid paralysis, loss of sensation, and loss of temperature regulation. Four phases have been proposed: – Phase 1 (0–24 hours post injury). Absent deep tendon reflexes (DTRs) and flaccid muscles that are largely due to a loss of supraspinal excitatory input. Impaired sympathetic innervation also occurs during this phase. – Phase 2 (1–3 days post injury). Initial reflex return via supersensitivity to neurotransmitters. – Phase 3 (4 days to 1 month post injury). Early hyperreflexia via replacement synapse growth; most DTRs reappear and acute hemodynamic perturbations improve during this phase. – Phase 4 (1–12 months post injury). Spasticity and hyperreflexia via continued synapse growth (axon-length-dependent timeframe) (2).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• SCI interferes with the ability of the spinal cord to autoregulate its blood flow, so perfusion becomes more pressure dependent (1). Additionally, concomitant injuries and neurogenic shock may compound hemodynamic perturbations. Secondary ischemic SCI is likely mitigated with supportive measures. – Maintain mean arterial BP in the high-normal range (> 90 mm Hg) (1)[B]. Based on studies in traumatic brain injury, blood pressure support is usually continued for the first 7 days after injury (1)[C]. – Avoid hypoxia (paO2 ≤60 mm Hg) (1)[C]. – Avoid acute anemia (1)[C]. • Special precautions during airway management may be required; discuss the cervical spine stability/clearance status with the spine surgeon. • Succinylcholine should be avoided after 48–72 hours of denervation states, as described below (3)[C].

PREOPERATIVE ASSESSMENT SYMPTOMS

• Inquire about motor and sensory function and the presence of dyspnea and/or increased work of breathing. • In the chronic SCI patient, inquire about hyperreflexia symptoms (e.g., headache or blurred vision with bowel/bladder distention).

History

Elicit the time and mechanism of SCI, level of cord injury, and rule out concomitant hypovolemic shock from blood loss and other injuries in the trauma patient. Signs/Physical Exam

• Perform a routine preanesthesia exam including a careful airway exam and assessment for cervical spine stability. • A detailed sensory and motor exam should be performed and documented in the acute post injury period as a baseline and to compare to the postoperative exam.

TREATMENT HISTORY

• Phase 1–2: Fluid resuscitation, blood product administration, and use of experimental hypothermia therapy. • Phase 3–4: Prior anesthetic records, including intubation details, and prior tracheostomy history.

MEDICATIONS

Phase 1–2: Vasopressors, vagolytics, and use and timing of corticosteroids (controversy exists regarding efficacy of glucocorticoids) (1).

DIAGNOSTIC TESTS & INTERPRETATION

Labs/Studies

• Basic metabolic panel, complete blood count, coagulation studies • Type and Screen/Cross, depending on expected blood loss • EKG (acute higher level SCI can interrupt sympathetic fibers and cause unopposed parasympathetic activity; bradycardia is common. Other arrhythmias have also been reported). • Chest x-ray (pulmonary edema is possible with aggressive fluid administration). • Serial vital capacity measurements and arterial blood gases to monitor for respiratory decompensation in nonmechanically ventilated patient with possible SCI-induced respiratory dysfunction. CONCOMITANT ORGAN DYSFUNCTION

• Cardiovascular dysfunction with neurogenic shock. A relative bradycardia may be present instead of the expected compensatory tachycardia with hypotension (1). This is most common within the first couple weeks after injury; bradycardia is most prevalent on Day 4 after injury (4). • Respiratory dysfunction (restrictive pattern) depending on the level of SCI. • Other traumatic injuries, such as subdural hemorrhage or thoracic, abdominal, and orthopedic injuries. CIRCUMSTANCES TO DELAY/CONDITIONS

Early emergent surgical decompression may be necessary. Unless the patient requires acute hemodynamic stabilization, emergency surgery should not be delayed.

TREATMENT PREOPERATIVE PREPARATION Premedications

• For recent trauma, patients are considered to have a full stomach. Drugs should be administered to decrease gastric fluid volume and increase gastric fluid pH (e.g., nonparticulate antacid, H2-receptor antagonist, and gastrokinetic agent). • If a fiberoptic intubation is planned, consider an antisialagogue to decrease secretions and improve visualization. • Determine if methylprednisolone has been administered or is being infused; NASCIS dosing (controversial) is 30 mg/kg bolus and 5.4 mg/kg/hour maintenance for up to 48 hours post injury (1).

Special Concerns for Informed Consent

• Acute SCI patient: Possible prolonged intubation and mechanical ventilation requirements depending on respiratory dysfunction; possible hemodynamic instability depending on the degree of neurogenic shock and concomitant injuries may require the placement of invasive monitors; patient counseling if awake intubation is planned. • Chronic SCI patient: Possible hemodynamic instability with autonomic hyperreflexia (may

require invasive monitoring).

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia for vertebral decompression. Avoid anesthetic techniques that interfere with the postoperative neurological exam. • For chronic SCI, consider regional or neuraxial techniques, as appropriate for the planned surgery.

Monitors

• Standard ASA monitors • In the acute post injury phase, placement of arterial lines (continuous blood pressure monitoring) and central venous catheters (assess preload, help guide fluid management, and administer vasoactive drugs) is routine (1)[C]. • Pulmonary artery catheterization may be considered depending on the degree of hemodynamic derangements. • Neuromonitoring (may include somatosensory and motor evoked potentials and electromyography) for spine surgery. • Decompress the stomach and bladder unless contraindicated since SCI can cause gastric paresis and/or dystonic bladder; organ distension may contribute to autonomic dysfunction.

Induction/Airway Management

• Maintain cervical spine immobilization for an uncleared spine. There is no outcome data to support one intubation technique over another (5)[C]. – Awake fiberoptic intubation with topical anesthesia allows the head and neck position to remain in a neutral position, maintains protective airway reflexes, and allows for neurological exam postintubation. – Direct laryngoscopy with manual in-line immobilization or other techniques can also be considered. – Application of cricoid pressure, if clinically indicated, is permissible in cervical spine injury (5)[C]. • Select a hemodynamically stable induction regimen (e.g., etomidate and ketamine). • Avoid succinylcholine for muscle relaxation after 48–72 hours of denervation states (risk of lethal hyperkalemia from up-regulation of muscle nicotinic acetylcholine receptors) (3)[C]. Many anesthesia providers avoid succinylcholine after even shorter durations (24 hours) of denervation states as a further precaution against hyperkalemia.

Maintenance

• Balanced technique with intravenous and/or volatile agents. Neuromonitoring may require limiting volatile agents and avoiding neuromuscular blocking agents. • Acute post injury phase: – Volume resuscitate to increase preload. Fluids may include crystalloids, colloid, and blood products. Optimal type of fluid therapy is unknown. However, hypotonic fluids are usually avoided since they can worsen cellular swelling. – Administer vasopressors to restore vasomotor tone and inotropes to increase cardiac

output. Choice of therapy depends on the hemodynamic condition of the patient; no specific algorithm exists to guide choice of therapy. – Intraoperative blood loss may be considerable and utilization of blood cell salvage is helpful.

Extubation/Emergence

• Prompt emergence is desired to facilitate a neurological exam. • Extubate when the patient is fully awake, following commands, and able to manage and protect their airway. Laryngeal edema may be present (especially after long spine surgery requiring large volume fluid resuscitation in the prone position); consider cuff-leak test prior to extubation. • Hypoxemia and endobronchial suctioning may worsen bradycardia from unopposed vagal stimulation (4).

FOLLOW-UP BED ACUITY

Invasive hemodynamic monitoring and support in the intensive care unit is usually continued for 7 days post injury, based on studies in traumatic brain injury (1)[C].

MEDICATIONS/LAB STUDIES/CONSULTS

Multidisciplinary care is required including neurosurgery and/or orthopedic surgery, critical care, physiatry, and social service management. COMPLICATIONS

• Pulmonary dysfunction: Consider aggressive chest physiotherapy and, if prolonged intubation/mechanical ventilation is anticipated, consider tracheostomy. • Venous thromboembolism: Consider mechanical and/or anticoagulant prophylaxis. • Skin breakdown: Prevent unnecessary pressure points and monitor contact areas. • Stress ulceration: Initiate prophylaxis with H2-receptor antagonist or proton pump inhibitor.

REFERENCES

1. Gupta R, Bathen ME, Smith JS, et al. Advances in the management of spinal cord injury. J Am Acad Orthop Surg. 2010;18:210–222. 2. Ditunno JF, Little JW, Tessler A, et al. Spinal shock revisited: A four-phase model. Spinal Cord. 2004;42:383–395. 3. Martyn JAJ, Richtsfeld M. Succinylcholine-induced hyperkalemia in acquired pathologic states. Anesthesiology. 2006;104:158–169. 4. Guly HR, Bouamra O, Lecky FE. The incidence of neurogenic shock in patients with isolated spinal cord injury in the emergency department. Resuscitation. 2008;76:57–62. 5. Crosby ET. Airway management in adults after cervical spine trauma. Anesthesiology. 2006;104:1293–318.

ADDITIONAL READING

• Fehlings MG, Rabin D, Sears W, et al. Current practice in the timing of surgical intervention in spinal cord injury. Spine. 2010;35:S166–173. • Veale P, Lamb J. Anaesthesia and acute spinal cord injury. BJA (CEPD Reviews). 2002;2:139–143. • Wuermser LA, Ho CH, Chiodo AE, et al. Spinal cord injury medicine. Acute care management of traumatic and nontraumatic injury. Arch Phys Med Rehabil. 2007;88:S55– 61.

See Also (Topic, Algorithm, Electronic Media Element)

• Neurogenic shock • Autonomic hyperreflexia/dysreflexia • Somatosensory and motor evoked potentials (SSEPs and MEPs)

CODES ICD9 958.4 Traumatic shock ICD10

T79.4XXA Traumatic shock, initial encounter

CLINICAL PEARLS

• Spinal shock is a transient loss of spinal cord function that can occur after acute SCI. Neurogenic shock, with hypotension and bradycardia, often coexists with spinal shock. • Secondary SCI may be mitigated with supportive measures. Avoid hypotension and hypoxia and maintain elevated mean arterial pressure.

SPIROMETRY

Timothy T. Tran, MD Ivan M. Kangrga, MD, PhD

BASICS DESCRIPTION

• Spirometry reflects respiratory mechanics. It describes the relationship between maximal forceful exhaled volume (following maximal inspiration) and time. – It is safe, inexpensive, and noninvasive. – Maximal and reproducible patient effort is essential for the accuracy of the test. • Spirometry, lung volumes, and diffusing capacity (DLCO) constitute pulmonary function testing (PFTs).

PHYSIOLOGY PRINCIPLES

• Spirometry reflects a complex interaction of respiratory muscle strength, elastic properties of the chest wall and lungs, and airway resistance. For example, forced exhalation reflects the ability of the expiratory muscles to overcome the outward force of the thorax. Spirometry cannot measure airway resistance directly, rather it is estimated based on expiratory flows. • Spirometry testing – During spirometry, patients are asked to breath normal tidal volumes (Fig.1), inhale maximally, and then exhale with maximal force (blast) and length of exhalation. – The generated graph is interpreted to determine key flow and volume parameters (Fig. 2).

FIGURE 1. Spirometry involves having the patient take a maximal inspiration after tidal breathing and then forcefully exhaling in what is referred to as a “blast exhalation.”

FIGURE 2. Generated graph from spirometry data delineates volumes, volume as a function of time, and flow rates.

• Spirometry parameters. Values are usually expressed as a percentage of normal values. Normal values are defined as mean ±2 SD based on height, age, gender, and ethnicity. – Forced vital capacity (FVC): Maximal volume forcibly exhaled following a maximal inspiration. – Forced expiratory volume in 1 second (FEV1): Single most important measure to determine significant obstructive pathology and to gauge its severity. – FEV1/FVC is the fraction of the vital capacity (VC) that can be exhaled in 1 second. It is a

key metric used to help distinguish between obstructive and restrictive patterns. Decreased values indicate obstruction whereas a normal or higher than normal ratio and reduced lung volumes suggest restrictive physiology. – Forced expiratory flow between 25% and 75% (FEF25-75%) of FVC reflects flow in small

airways; it is not effort dependent. The large variability of normal values limits applicability. – Peak expiratory flow (PEF): Used to monitor responsiveness to bronchodilators; flow must be maintained for at least 10 ms.

ANATOMY

• Inspiratory muscles – Diaphragm: Innervated by the phrenic nerve (C3–C5). Responsible for one-third of the tidal volume when upright and two-third when supine. During contraction, the dome descends (up to 10 cm), elongating the thorax and increasing intra-abdominal pressure. – External intercostals (intercostal nerves) and accessory muscles (scalene muscles, C4–C8; and sternocleidomastoid, CN XI) both increase the anteroposterior and transverse diameters of the chest. • Expiratory muscles – During spontaneous ventilation, expiration at rest is passively driven by the elastic recoil. Inspiratory muscles are relaxed, and no muscles contract. – During spontaneous ventilation, active expiration (exercise, singing) is generated by the muscles of the abdominal wall and internal intercostals.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Spirometry is not a diagnostic test; it reveals respiratory mechanical patterns. These patterns should be reconciled with clinical diagnosis and other diagnostic tests. Once the specific

diagnosis is known, spirometry is used to quantify the severity of disease and monitor the progress of therapy. • Obstructive pulmonary disease (OPD) is characterized by decreased airway flow: Both FEV1 and FEV1/FVC are decreased (FVC is typically normal or increased). The course of disease

and response to therapy is best followed by changes in FEV1 (1)[B].

– Emphysema is characterized by enlargement of the airspaces and obstructive chronic bronchitis (OCB) is characterized by excessive mucus production in the bronchi. Severity is assessed per the Global Initiative for Obstructive Lung Disease (GOLD) criteria. Key differential: DLCO is reduced in emphysema but not in OCB. – Asthma is characterized by airway obstruction, inflammation, hyperresponsiveness to triggers, and the following symptoms: Wheezing, dyspnea, cough, and chest tightness. Diagnostic criteria for asthma: Reduced FEV1/FVC (with no specific ratio); and reversible airflow impairment, defined as an improvement of >12% (or >0.2 L) in FEV1 or FVC.

Lack of response does not automatically rule out the diagnosis, as some patients require more aggressive intervention to demonstrate reversibility. Parenchymal gas exchange is preserved to a greater extent than in emphysema, evident by a normal or increased DLCO.

• Restrictive pulmonary disease is characterized by decreases in FVC and either normal or increased FEV1/FVC.

– Interstitial disease (e.g., pulmonary fibrosis) causes decreases in lung volumes, with normal or elevated flow ratios, but decreased DLCO, PaO2, and PaCO2.

– Kyphosis and scoliosis: Depending on severity, may have decreased FVC, FEV1, or both.

– Neuromuscular disorders (amyotrophic lateral sclerosis, multiple sclerosis, Duchenne’s muscular dystrophy, myasthenia gravis): Reduced FVC often correlates with severity of disease. Maximal inspiratory and expiratory flows detect muscle weakness. – Habitus Obesity: Decreased chest wall compliance and increased large and small airway resistance result in decreased FVC and FEV1. Also, reduction in volumes and V/Q mismatching. Pregnancy: Usually normal spirometry but changes in lung volumes do occur.

PERIOPERATIVE RELEVANCE

• Postoperative pulmonary complications result in prolonged hospital stay and increased health costs (2)[B]. – Reduced lung volumes due to diaphragmatic dysfunction, splinting from pain, respiratory depressant effects of narcotics, and impaired mucociliary clearance are the main mechanisms of pulmonary complications. – These changes promote postoperative atelectasis, pneumonia, and V/Q mismatches. For example, after thoracic or upper abdominal surgery, FVC and FRC may be reduced up to 60% and 30%, respectively, and can last for 1–2 weeks. Lower abdominal surgery is associated with similar changes but to a lesser degree (3)[B]. • Thoracic surgery: Spirometry is indicated in all patients undergoing lung resection, but for

nonlung thoracic surgery it is not always required. (Note: ppo = predicted postoperative) – Patients with FEV1 >2 L (>80% predicted) tolerate pneumonectomy and those with FEV1

>1.5 L (>60% predicted) can undergo lobectomy (4)[B]. – Increased risk is seen if the FEV1 is <1.5 L; FEV1 <800 mL is generally considered prohibitive for lung resection; a calculated ppoFEV1 <40% suggests an increased risk,

<30% high risk – In borderline patients, DLCO and calculated ppoDLCO (Equation 2) refine the above by

assessing parenchymal function; a ppoDLCO <40% is associated with high risk and <20%

with unacceptable risk. – When FEV1 and DLCO are >80% predicted, no further testing is required. For borderline values, integrated cardiopulmonary testing (VO2max) may be indicated.

– The difficulty of assigning a specific test value prohibitive for lung surgery stems from diversity in patient population (age, sex, gender, race) and variable severity of disease of the remaining lung (e.g., lack of homogeneity of lung disease). • Perioperative spirometry can aid with risk stratification and planning of risk modification interventions, with the goal of decreasing complications in at-risk patients. Routine testing is NOT indicated in asymptomatic or low-risk patients undergoing nonthoracic, nonabdominal surgery. A thorough history and physical remain the most important tools for perioperative risk assessment. It may be appropriate for: – Dyspnea or exercise intolerance of unexplained etiology to differentiate between pulmonary and cardiac causes – Chronic obstructive pulmonary disease (COPD) or asthma where clinical evaluation cannot determine if therapy is optimized – In general, patients have a high risk for postoperative pulmonary complications when there is an FVC <50% of predicted; FEV1 <50% of predicted, FEV1 <1 L, or postoperative FEV1 <40% of predicted; or significant hypoxemia (paO2 <60 mm Hg) or

hypercapnia (paCO2 >45 mm Hg).

• Perioperative risk modification strategies in patients with increased risk of complications (5) [B] include – Preoperative optimization: Asthmatics should have their symptoms controlled prior to surgery, peak flows >80% predicted, or personal best. Anticholinergics and beta-2 agonists given in meter-dosed inhalers are effective. Corticosteroids are useful and are not associated with increased incidence of perioperative infection. COPD: Symptom and exacerbation control and optimization – Use regional anesthesia technique if possible to avoid airway instrumentation. – Consider a thoracic epidural for thoracic or abdominal surgery to optimize postoperative pain control. This allows for deep breathing, incentive spirometry, and return to early ambulation. – Use of nonopioid analgesia when applicable; opioids depress the respiratory drive and can increase the paCO2.

– Avoid neuromuscular blockade if possible; when utilized, ensure that the patient is fully reversed. – Lung protective ventilation strategy includes tidal volumes <8 mL/kg, pressure controlled ventilation, inspiratory pressure <35 cm H2O, PEEP 4–10 cm H2O, and occasional

recruitment maneuvers should be considered. – Careful adjustment of the I:E ratio and ventilatory rate can minimize air trapping (ensures that inspiration starts at FRC). – Intraoperative delivery of bronchodilators and meticulous pulmonary toilette. – Bronchospasm can be treated by increasing the depth of inhaled anesthetic, administering bronchodilators (albuterol, ipratropium); meter-dosed inhalers appear to have better medication delivery compared to nebulizers. – Avoidance of irritating agents such as desflurane during induction and emergence helps prevent bronchospasm. – Postoperative planning should include adequate monitoring of the environment and the use of noninvasive or invasive ventilatory support.

EQUATIONS

• Predicted postoperative FEV1: ppoFEV1% = FEV1% × (1–fraction of functional lung tissue

removed) • Predicted postoperative DLCO: ppoDLCO% = DLCO% × (1–fraction of functional lung tissue removed). The fraction of functional lung tissue that will be removed can be estimated by CT or ventilation/perfusion scan.

REFERENCE

1. ayes D, Kraman SS. The physiologic basis of spirometry. Respir Care. 2009;54(12):1717– 1726. 2. Colice GL, et al. Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: ACCP evidence-based clinical practice guidelines (2nd edn). Chest. 2007;132:161S. 3. hetta A, et al. Changes in lung function and respiratory muscle strength after sternotomy vs. laparotomy in patients without ventilatory limitation. Eur Surg Res. 2006;28:489–493. 4. Rock P, Rich PB. Postoperative pulmonary complications. Curr Opin Anaesthesiol. 2003;16:123–132. 5. Lawrence VA, et al. Strategies to reduce postoperative pulmonary complications after noncardiothoracic surgery: Systemic review for the American College of Physicians. Ann Intern Med. 2006;144:596–608.

ADDITIONAL READING

• Ault ML, Stock MC. Respiratory Function. Clinical Anesthesia. 6th edn. Philadelphia: Lippincott Williams & Wilkins, 2009. • West JB. Pulmonary Pathophysiology: The Essentials. 6th edn. Philadelphia: Lippincott Williams & Wilkins, 2003.

See Also (Topic, Algorithm, Electronic Media Element) • Flow volume loops • Pulmonary function tests • Functional residual capacity • Asthma • Chronic bronchitis

CLINICAL PEARLS

• The use of perioperative spirometry is not based on randomized controlled studies; therefore, routine preoperative testing is not indicated. • Spirometry alone is not diagnostic and should not be the sole reason to exclude surgical candidacy. The history and physical remains the best tool for perioperative risk assessment. • Spirometry temporarily increases pressures in the thorax, abdomen, cranium, and eyes. Spirometry causes exertion and should be used with caution in recent MI or angina.

SPLENECTOMY Emily L. Drennan, MD

BASICS DESCRIPTION General

• A normal spleen in an adult weighs ∼5 ounces and has dimensions of 5×3×6 inches. Normal functions include filtration of blood as well as production of immune opsonins and other complement components. • Splenectomies are performed for the following indications: – Spherocytosis – Metastatic malignancy – Splenic trauma – Idiopathic thrombocytopenic purpura (ITP) – Thrombotic thrombocytopenic purpura (TTP) – Spherocytosis – Sickle cell disease – Lymphoma – Splenic abscess – Splenic cyst – Splenic vein thrombosis – Cirrhosis of the liver – Esophageal varices • Splenectomies may be performed through an open incision or laparoscopically, with the latter approach preferred as long as the size of the organ is not an issue. • Open splenectomy involves identifying and dissecting the short gastric vessels, splenocolic ligament, and inferior pole vessels. The vessels are ligated at the hilum, the spleen is freed from the diaphragm and then removed from the abdomen. Bleeding is assessed and controlled and the incision is closed. • Laparoscopic splenectomy starts with the patient in the reverse Trendelenburg position. Three or four 10 mm ports are placed into the abdomen. The dissection of the spleen is carried out as in the open procedure. When the spleen is free, it is either morcellized and removed in a collection bag or removed whole via an enlarged incision. • Accessory spleens may be present in up to 20% of patients. In patients undergoing splenectomy for a hematologic disorder, they may not be cured by splenectomy as anticipated. • Alternate techniques for patients in whom surgical splenectomy is contraindicated (due to significant comorbidities) treatment include radiofrequency ablation (RFA) of the spleen or splenic artery embolization. Additionally, these procedures may also be performed prior to a splenectomy to decrease the size or blood supply.

• Partial splenectomy may be performed to retain the important immune functions of the organ. The goal is to retain at least 25% of the splenic mass of a normal spleen.

Position

• Open: Supine • Laparoscopic: Semilateral position, left arm extended over head

Incision

• Open: Midline or left subcostal • Laparoscopic: Four or five 1 cm incisions, one at the umbilicus as the camera port, and the others in the left upper quadrant for instrumentation.

Approximate Time

• Approximately 45–60 minutes; longer if the spleen is particularly enlarged or the patient has had previous upper abdominal surgery. • Laparoscopic cases are longer, up to 2 or 3 hours

EBL Expected 100–300 mL

Hospital Stay

• Open: 5–7 days • Laparoscopic: 1–3 days

Special Equipment for Surgery

Immunization against pneumococcus, meningococcus, and Haemophilus influenzae should be performed prior to surgery, if possible. EPIDEMIOLOGY Prevalence

• The number of splenectomies have significantly decreased over the past 20 years with the recognition of morbidities resulting from asplenia. Surgeons are more likely to attempt to salvage a damaged spleen in order to preserve the patient’s immune function. • The National Surgical Quality Improvement project indicates that 2,167 procedures were performed in the US during the years of 2005–2008.

Prevalence

ITP affects ∼90,000 people in the US and Europe and is the most common non-trauma indication for splenectomy. Morbidity

• Dependent on the indication for the procedure. • Morbidity for trauma patients is dependent on other injuries present. • Open approach is 28.9% and laparoscopic is 11.7%. • Most common morbidity is atelectasis, present in ∼25% of patients undergoing abdominal surgery.

Mortality

Operative mortality is <1%.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Maintain adequate muscle relaxation to facilitate exposure, the creation/maintenance of the pneumoperitoneum, and the removal of an enlarged spleen through a small abdominal incision. • Provide blood component transfusion as needed to maintain hemostasis, particularly platelet transfusion.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Left upper quadrant pain or fullness • Early satiety as the spleen compresses the stomach

History

• Splenic trauma • Underlying pathology for spleen removal (e.g., sickle cell disease)

Signs/Physical Exam

• Palpation of the enlarged spleen in the right upper quadrant • Generalized lymphadenopathy may be present if cause is immune related • Bruit over the left upper quadrant or epigastrium related to splenic congestion

MEDICATIONS

Preoperative vaccination against pneumococcus, meningococcus, and H. influenzae is indicated. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Ultrasound may confirm an enlarged spleen. • Nuclear scan may identify an accessory spleen. • Preoperative CBC is indicated to assess for anemia and platelet count.

CONCOMITANT ORGAN DYSFUNCTION

May include immunodeficiency or liver dysfunction depending on the procedure indication

TREATMENT PREOPERATIVE PREPARATION Premedications

Preoperative vaccinations, especially pneumococcal vaccine

Special Concerns for Informed Consent

• If the planned procedure is laparoscopic, the surgical consent should also include “possible” open approach, as well. • A discussion about postoperative pain management should include the possibility of an epidural, and the associated risk, especially in patients with thrombocytopenia. For scheduled laparoscopic procedures, a discussion for postoperative placement may be made in the event that it is converted to an open incision.

Antibiotics/Common Organisms

• Preoperative antibiotics to cover skin flora are indicated, such as a first-generation cephalosporin or clindamycin. • Postoperative antibiotic prophylaxis is controversial. It is generally indicated in children <5 years of age, but not in adults. Other groups such as those with underlying immune deficiencies may benefit from postoperative oral penicillin prophylaxis, but the data is not clear. • Common organisms involved in postoperative infections include – Encapsulated bacteria – Staphylococcus aureus – Gram-negative organisms – Malaria – Babesiosis

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia • Epidural placement for postoperative pain in open procedures, particularly if the splenectomy is performed as part of a staging laparotomy with a large midline abdominal incision. Patients with thrombocytopenia (TTP, ITP) or other coagulopathies (liver disease with varices) may not be appropriate candidates.

Monitors

• Standard ASA monitors • Arterial line may be indicated for patients with significant comorbid disease or massive hypersplenism.

Induction/Airway Management

• Standard induction • A cuffed endotracheal tube is necessary for both open and laparoscopic procedures

Maintenance

• A nasogastric tube should be placed after induction to decompress the stomach, enhance surgical exposure, and facilitate the isolation of short gastric arteries from the stomach to spleen. • Choice of inhalation agent and muscle relaxant to facilitate surgical exposure.

• Insufflation for laparoscopy leads to reduced lung compliance. 15 mm Hg is the typical intra-abdominal pressure, but this may be decreased if it is necessary to improve ventilation. • Reverse Trendelenburg positioning is utilized to allow abdominal displacement with gravity. This can improve some of the respiratory parameters (peak inspiratory pressures, functional residual capacity, lung compliance), but decrease cardiac preload. • Thromboelastography, if available, can be used to guide platelet transfusion intraoperatively.

EXTUBATION/EMERGENCE

• Standard criteria for extubation. • In an open splenectomy, the nasogastric tube is left postoperatively to continue gastric distention. In laparascopic cases, it may not be necessary to leave after extubation (depends on surgeon’s preference).

FOLLOW-UP BED ACUITY

• Open splenectomy carries a high risk for postoperative atelectasis and diaphragmatic dysfunction. • Overwhelming post-splenectomy sepsis is mostly likely to present in the immediate postoperative period. It presents as fever, bacteremia, coagulopathy, and progresses rapidly to shock; thus, requires emergent treatment.

ANALGESIA

• Patient controlled analgesia • Ketorolac if no other contraindication • Epidural catheter bolus and infusion

COMPLICATIONS

• Hemorrhage • Overwhelming post-splenectomy sepsis • Chronic thrombocytosis • Portal vein thrombosis • Pancreatitis • Left lower lobe atelectasis • Wound infection • Subphrenic abscess • Postoperative hypercoagulable state

Pediatric Considerations

• The rate of overwhelming post-splenectomy sepsis in children <5 years of age is significant. Infants <1 year of age have a 10% risk (highest risk). • The risk of post-splenectomy sepsis remains high for the first 2 years after the procedure is performed.

PROGNOSIS

• Generally excellent and mostly related to underlying disease state and injuries. • Post-splenectomy thrombocytosis is treated with aspirin or hydroxyurea. However, the benefit is not clear. • Overwhelming post-splenectomy sepsis carries a mortality rate of 50–70% and is considered a medical emergency. • Data indicates that splenectomy may increase the lifetime risk of developing pulmonary hypertension.

REFERENCES

1. Kyaw MH, et al. Evaluation of severe infection and survival after splenectomy. Am J Med. 2006;119(3):276.

2. Schutze GE, et al. Invasive pneumococcal infections in children with asplenia. Pediatr Infect Dis J. 2002;21(4):278–282. 3. Watters JM, Sambasivan CN, Zink K, et al. Splenectomy leads to a persistent hypercoagulable state after trauma. Am J Surg. 2010;199(5):646–651. See Also (Topic, Algorithm, Electronic Media Element) • Trauma • Sickle cell disease • Thrombocytopenia • Laparoscopy

CLINICAL PEARLS

• The majority of splenectomies that are performed today are laparoscopic, with chronic ITP being the most common indication. • The greatest morbidity results from postoperative sepsis, especially in children. • Despite the benefits of an epidural for postoperative analgesia, it may be contraindicated in thrombocytopenic or coagulopathic patients.

SUBCLAVIAN STEAL SYNDROME Rongjie Jiang, MB, MS Jeffrey J. Schwartz, MD

BASICS DESCRIPTION

• Subclavian steal syndrome is a phenomenon of transient cerebral ischemic attacks following ipsilateral arm exercise in the presence of severe stenosis (>80%) or occlusion of the subclavian artery proximal to the origin of the vertebral artery. – During exercise, blood flows retrograde from the ipsilateral vertebral artery to the distal subclavian artery to supply the arm; in doing so, blood is diverted from the circle of Willis and can result in transient cerebral ischemia. • Coronary–subclavian steal syndrome is a rare complication following use of the left internal mammary artery (LIMA) graft for coronary artery bypass (CABG) in the presence of severe proximal stenosis in the left subclavian artery. This may produce reversal of blood flow from the heart to the ipsilateral arm during exercise that leads to angina pectoris. PHYSIOLOGY PRINCIPLES

• Subclavian steal is a flow-related phenomenon. – At rest, when a proximal occlusion develops in the subclavian artery, the arm becomes dependent on the collateral vessels from the head, shoulder, and neck, particularly retrograde flow from the ipsilateral vertebral artery. – When the arm is exercised, the blood vessels dilate and create a low resistance vascular bed. More blood flows from the contralateral vertebral artery to the basilar artery and there is increased retrograde flow into the ipsilateral vertebral artery down to the subclavian artery to supply the arm. • Coronary–subclavian steal can happen when patients have a coronary bypass using an in situ LIMA graft, in conjunction with significant stenosis in the proximal left subclavian. Thus, retrograde flow can occur and direct the blood away from the heart to the arm.

ANATOMY

• Normally, BPs are similar in both arms. A significant discrepancy raises a possibility of stenosis in a subclavian artery, or coarctation of the aorta. • The vertebral arteries arise from the superior aspect of the proximal subclavian artery and feed into the basilar artery, which is part of the circle of Willis. • The cerebral collateral conduits are mainly formed by the circle of Willis. It is an arterial ring surrounding the optic chiasma and hypothalamus. – Anteriorly, it is formed by the left and right anterior cerebral arteries that arise from the left and right internal carotid arteries; they are “linked” by the anterior communicating arteries. – Posteriorly, it is formed by the division of the basilar artery into the left and right

posterior cerebral arteries. – Laterally, the left and right posterior communicating arteries join the left and right posterior cerebral arteries to the internal carotid arteries. • The internal mammary artery arises from the inferior aspect of the proximal subclavian artery, opposite the vertebral artery.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The most common cause of proximal occlusive lesions in the subclavian arteries is atherosclerosis. The most common sites are the – Left subclavian artery (62%) – Right subclavian artery (28%) – Right innominate artery (10%) – Other less common causes include Takayasu disease Temporal arteritis Status post surgical repair of coarctation of the aorta Congenital lesions of the aortic arch or subclavian artery Status post Blalock–Taussig procedure for tetralogy of Fallot Compression of the subclavian artery in the thoracic outlet • Not all retrograde flow through the vertebral artery leads to neurologic symptoms; the majority of time it is asymptomatic. It usually only becomes symptomatic when occlusive lesions in the cerebral collateral conduits are present. 80% of patients with subclavian steal syndrome have contralateral vertebral or carotid disease. • Neurological symptoms in subclavian steal syndrome usually resolve after discontinuing exercise of the arm. Common symptoms include – Vertigo (50%) – Diplopia (19%) – Syncope (18%) – Dysarthria (12.5%) – Ataxia – Blurring of vision – Perioral numbness – Paresthesia – Infarction is rare • Other symptoms: – Exercise-induced arm pain – Absent or diminished pulse in the ipsilateral arm and a significantly unequal systolic BP from one side to the other (>20 mm Hg). – Bruit in the supraclavicular fossa • A recurrence of angina in a patient who has had a coronary bypass using a LIMA graft with presence of stenosis in the proximal left subclavian artery indicates a possibility of coronary–subclavian steal.

PERIOPERATIVE RELEVANCE

• The most common etiology is atherosclerosis. Thus, subclavian stenosis is associated with an

increased total mortality and cardiovascular disease mortality after adjusting for common risk factors (2). They share the same risk factors as those with coronary artery disease: – Advanced age – Male sex – Family history – Cigarette smoking – Hypercholesterolemia – Diabetes mellitus – Hypertension – Hyperhomocysteinemia • Less common etiologies need to be identified if present. They may dictate special anesthetic planning and special requirements on intraoperative monitoring. • Diagnostic studies are done not only to confirm the diagnosis but also to ensure patent proximal common carotid and distal subclavian arteries and to rule out any coexisting lesions in the collateral pathways. – Duplex ultrasonography (combined two-dimensional ultrasound and pulse-wave Doppler) of the neck arteries. A coexisting severe carotid stenosis generally requires that a carotid endarterectomy be performed first and then a reevaluation of any persistent neurologic symptoms be made. – Four-vessel cerebral angiography – CT angiography – Magnetic resonance angiography in patients with renal insufficiency • Conservative treatment includes controlling hypertension, lipid modification, glycemic control in diabetes, smoking cessation, and antiplatelet treatment with aspirin. • Surgical treatment is only indicated for symptomatic patients. – Endovascular angioplasty and/or stenting of the subclavian artery has a success rate of 86–93%. The complication rate is about 3–17%. The restenosis rate is about 0–16% in stenting after 12–48 months. Stenting requires postoperative aspirin and clopidogrel for 6–12 months to reduce the risk of restenosis. – Extrathoracic carotid–subclavian bypass (using a prosthetic conduit) requires a brief period of complete clamp of the carotid artery for anastomosis that is usually well tolerated. An intraluminal shunt is necessary only if there are significant lesions in the contralateral common or internal carotid arteries. – Extrathoracic subclavian transposition (subclavian to carotid anastomosis) requires more extensive dissection compared to carotid–subclavian bypass. Phrenic nerve injury or the thoracic duct injury is possible. – Axillary-axillary bypass can be done when there is significant ipsilateral carotid disease. The prosthetic graft is usually placed underneath the skin overlying the sternum. A sternotomy after an axillary-axillary bypass would put the graft at risk. – Subclavian endarterectomy requires thoracotomy and is rarely performed. • Postoperative monitoring: – Bleeding in the access site – Neurological status (cerebral ischemic events from thrombosis of the target vessel or distal embolization up the carotid or vertebral arteries)

– Check BP in both arms • To prevent coronary–subclavian steal syndrome, it is crucial to rule out any high-grade proximal stenosis in the left subclavian artery before LIMA is considered as a graft (3). At a minimum, bilateral upper extremity noninvasive BP should be checked. A difference of 15 mm Hg identifies all patients with subclavian stenosis of >50% (4). If present, stent the subclavian artery prior to CABG, then use an in situ LIMA graft. In an emergent setting, a free LIMA graft to LAD appears to be a reasonable choice (1). GRAPHS/FIGURES

FIGURE 1. Blockage of the subclavian artery proximal to the vertebral artery. During exercise, blood vessels in the arm dilate (decrease resistance). Blood from the cerebral vasculature flows preferentially in the direction of decreased resistance and retrograde down the vertebral artery. This results in “steal”.

REFERENCE

1. ogers JH, Calhoun RF. Diagnosis and management of subclavian artery stenosis prior to coronary artery bypass grafting in the current era. J Card Surg. 2007;22(1):20–25. 2. Aboyans V, Criqui MH, McDermott MM, et al. The vital prognosis of subclavian stenosis. J Am Coll Cardiol. 2007;49(14):1540–1545. 3. Hwang HY, Kim JH, Lee W, et al. Left subclavian artery stenosis in coronary artery bypass: Prevalence and revascularization strategies. Ann Thorac Surg. 2010;89(4):1146–1150. 4. Osborn LA, Vernon SM, Reynolds B, et al. Screening for subclavian stenosis in patients who are candidates for coronary bypass surgery. Catheter Cardiovasc Interv. 2002;56(2):162– 165. 5. Osiro S, Zurada A, Gielecki J, et al. A reivew of subclavian steal syndrome with clinical correlations. Med Sci Monit. 2012;18(5):RA57–RA63. 6. choa VM, Yeghiazarians Y. Subclavian artery stenosis: a review for the vascular medicine practitioner. Vasc Med. 2011;16(1):29–34.

ADDITIONAL READING

• Burlhan E, Soma F, Iared W. Angioplasty versus stending for subclavian artery stenosis. Cochrane Database Syst Rev. 2011; 5(10):CD008461.

See Also (Topic, Algorithm, Electronic Media Element) • Circle of Willis • Coronary artery disease • Peripheral artery disease

CODES ICD9

435.2 Subclavian steal syndrome ICD10 G45.8 Oth transient cerebral ischemic attacks and related synd

CLINICAL PEARLS

• A difference of 15 mm Hg in bilateral upper extremity brachial artery BP readings identifies all patients with subclavian stenosis of >50%. • The majority of patients with proximal subclavian stenosis are asymptomatic even when there is retrograde flow from the ipsilateral vertebral artery. It requires only conservative management.

SUBSTANCE ABUSE AND PREGNANCY Chitra Ramasubbu, MD

BASICS DESCRIPTION

• The sequelae of substance abuse superimposed on the physiological changes of pregnancy can have serious consequences to both the mother and fetus. • Commonly abused substances in pregnancy include cocaine, amphetamines, opioids, marijuana, alcohol, and tobacco. Opioid abuse includes morphine, meperidine, heroin, fentanyl, and methadone. • Alcohol use is a leading cause of preventable birth defects and developmental disabilities in the US. • There is a need for prevention strategies for at-risk parturients. Psychological and social comorbidities must be thoroughly evaluated in this subset of parturients EPIDEMIOLOGY Prevalence

• There has been an increase in substance abuse during pregnancy over the past three decades. • The incidence of fetal alcohol syndrome (FAS) is 3.7 cases per 10,000 live births.

Prevalence

• Prenatal illicit drug abuse is estimated at ∼5% in the US. However, it may be significantly higher than estimated due to inadequate reporting. • Smoking is estimated to be <10%. Of note, 90% of opioid-dependent women are also heavy smokers. • Alcohol abuse in the parturient population is about 12% and binge drinking occurs in ∼3% of pregnancies. • FAS ranges from 0.5 to 2 cases per 1,000 live births.

Morbidity/Mortality

• The Health Resources and Services Administration (HRSA) suggests a 40% increase in the risk of death during the first year of life in infants with frequent smoke exposure. • Fetal alcohol exposure is the leading cause of preventable birth defects and developmental disorders in the US. • Heavy alcohol intake increases the overall neonatal mortality by 18%. • Women who use drugs such as cocaine during pregnancy have more than twice the risk of delivering a preterm, low birth weight baby than those who do not. They are also five times more likely to have a baby with a birth defect. • Neonatal abstinence syndrome (NAS) is seen in up to 94% of neonates with intrauterine opioid exposure; it is present in up to 60–80% of neonates exposed to maternal methadone.

ETIOLOGY/RISK FACTORS

• Drug use varies by race/ethnicity with nonwhite women being twice as likely as Caucasian parturients to use illicit drugs. • A strong predictor of alcohol and tobacco use during pregnancy is their use prior to pregnancy. • Lack of prenatal care, history of premature labor, and tobacco use are associated with substance abuse. • There is a high rate of psychiatric illnesses in substance-dependent women including anxiety (32%) and depression (30%). • There is a strong correlation between childhood abuse in mothers and later drug dependence.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The mechanism of action depends on the substance abused. • Alcohol abuse affects every organ in the body. It affects several neurotransmitters including GABA, glutamate, serotonin, and dopamine resulting in its euphoric, anxiolytic, and sedative effects. Long-term ingestion results in an increase in glutamate receptors, which on alcohol withdrawal result in an excitatory state. – FAS involves a spectrum of symptoms including characteristic facial appearances, growth restriction, neurotoxicity, and cardiovascular abnormalities. There is no safe level of alcohol consumption. Regardless of the gestational period, these adverse effects can occur. • Tobacco exposure leads to tissue destruction and cellular changes that contribute to organ damage. It dramatically increases the prevalence of cardiovascular and pulmonary disease processes higher than in the mother. – Consequences include hypotrophic placenta, placental vasoconstriction leading to spontaneous abortion, fetal growth restriction, and low birth weight. – Nicotine crosses the placenta reaching fetal concentrations 15% higher than those of mother. It is also transferred via breast milk. • Cocaine blocks the presynaptic uptake of sympathomimetic neurotransmitters like norepinephrine, serotonin, and dopamine resulting in prolonged adrenergic stimulation. It is lipophilic and rapidly diffuses through the placenta. – Fetal complications result from maternal vasoconstriction leading to uteroplacental insufficiency, acidosis, and hypoxia. Cocaine is teratogenic as well. – Maternal complications include premature labor, placental abruption, uterine rupture, cardiac arrhythmias, cardiac ischemia/infarction, stroke, and death. • Amphetamines are indirect sympathomimetic drugs that cause euphoria, appetite suppression, and increased alertness. It may be difficult to distinguish from cocaine intoxication. Maternal complications of ingestion include premature labor, placental abruption, uterine rupture, cardiac arrhythmias, cardiac ischemia/infarction, stroke, and death. • Marijuana has a complex mechanism of action with an unpredictable clinical picture. There is no evidence of teratogenicity reported. However, low birth weight, delay in cognitive development, and complications during labor have been reported. • Opioid abuse can result in NAS that is characterized by a variety of symptoms including

fevers, poor sucking, stuffy nose, excessive crying, yawning, tremor, hyperexcitability, sneezing, vomiting, and diarrhea in the fetus. The IV mode of administration increases the mother’s risk of endocarditis, malnutrition, cellulitis, skin abscesses, hepatitis, and HIV infections.

PREVENTATIVE MEASURES

• The anesthetist does not have an extensive role in the prevention of parturient substance abuse; however, they should be aware of treatment and prevention modalities that may affect the patient’s peripartum care. • Abstinence is ideal; however, most opioid-dependent women cannot remain drug free throughout pregnancy. This may result in relapse with cycles of intoxication and withdrawal that leads to fetal distress. – Methadone maintenance is the gold standard in opioid-dependent parturients, although the drug is not approved for use during pregnancy. – Evidence shows that parturients on methadone have higher follow-up rates, improved prenatal care, and reduced fetal morbidity and mortality. – Buprenorphine maintenance therapy has been shown to be safe in the mother and fetus and may be an alternative for the treatment of opioid-dependent women in pregnancy. • Psychosocial intervention and counseling play an important role. This includes establishing an appropriate living environment and settling financial problems. • Psychiatric medications may be appropriate; there is a high rate of psychiatric illnesses in substance-dependent women including anxiety (32%) and depression (30%). SSRIs are widely used to treat major depression and anxiety in this population. Such patients should be carefully monitored for serotoninergic toxic effects. • Tobacco abstinence of 4–6 weeks decreases postoperative respiratory morbidity to nonsmoker levels.

PREOPERATIVE ASSESSMENT • History: Most parturients with a history of drug abuse deny it. A lack of prenatal care, history of premature labor, and smoking should evoke a high index of suspicion for substance abuse. • Signs and symptoms depend on the type of substance abused, route of administration, and frequency of use. • Cocaine: Tachycardia, hypertension, cardiac arrhythmias; confusion, hyperreflexia, fever, dilated pupils, proteinuria, edema, and seizures. • Amphetamines: Confusion, hyperreflexia, fever, dilated pupils, proteinuria, edema, and seizures. • Alcohol withdrawal: Tremors, hypertension, confusion, agitation, hallucinations, nausea, tachycardia, and arrhythmias. Acute withdrawal occurs after 6–48 hours of abstinence. Delirium tremens can occur from 2 to 10 days after the last drink. • Acute marijuana use: Tachycardia, nasal, or conjunctiva congestion. • Opioid overdose: Respiratory depression, miotic pupils, lethargy, and sedation. • Opioid withdrawal: Mydriasis, restlessness, tachycardia, tachypnea, hypertension, lacrimation, rhinorrhea, yawning, and piloerection. Withdrawal symptoms usually occur 4–

6 hours after the last opioid dose and peak at 48–72 hours. • Alcohol screening tools. – T-ACE: Tolerance, Annoyed by criticisms, having felt the need to Cut down, Eye opener in the morning. – TWEAK: Tolerance, Worry by family member, Eye opener, Amnesia, Kut down. • Maternal urine toxicology screening can be used to identify the recent use of illicit substances. Cocaine metabolites are seen in maternal urine for 24–60 hours after drug administration. • Analysis of fetal urine may serve as a marker as well.

DIFFERENTIAL DIAGNOSIS

• Differentiating between the symptoms of substances abused is difficult when multiple substances are involved. • In the presence of cognitive decline or focal deficits, gross structural brain disorders like head trauma or spontaneous bleeds must be ruled out. • Hypertension, proteinuria and convulsions seen in cocaine or amphetamine intoxication may be mistaken for preeclampsia or eclampsia. Liver and kidney dysfunction may be present in preeclampsia, whereas, a positive urine toxicology screen can help distinguish cocaine or amphetamine abuse. • Symptoms of alcohol/benzodiazepine withdrawal may resemble cocaine or amphetamine intoxication.

TREATMENT • IV access may be difficult; central vein access may be required. • Standard ASA monitors (pulse oximetry, NIBP, EKG, temperature monitoring) for laboring epidurals may be necessary. • Invasive monitors including an arterial line, central venous pressure and/or pulmonary artery catheter (rarely) may be indicated in parturients with a high risk of bleeding, uncontrolled hypertension, or severe hypotension. • Regional anesthesia – Preferred in smokers secondary to the pulmonary effects of tobacco that include increased secretions, decreased ciliary motility, impairment of gas exchange, and bronchospasm. – Infection may preclude placement. – Adequate fluid resuscitation is essential prior to placement. – Direct-acting sympathomimetics (phenylephrine) may be necessary to treat hypotension. Depleted catecholamine stores (seen with chronic cocaine and amphetamine use) can result in a resistance to ephedrine (indirect method of action). • General anesthesia – Emergent delivery of the neonate may be necessary in cases of fetal and maternal instability. – Aspiration prophylaxis should be implemented. – Be prepared to treat hypertension, cardiac arrhythmias, and myocardial ischemia. – Drugs and fluids should be carefully administered in the setting of cardiac failure or

hepatic dysfunction; consider invasive monitoring. – Marijuana use compounded with volatile agents may result in profound myocardial depression. – Acute intoxication with CNS depressants (benzodiazepines, alcohol, and opioids) requires a reduced amount of anesthetic. – Acute intoxication with CNS stimulants (cocaine or amphetamine) requires an increased amount of anesthetics. • Altered pain perception may result from changes in the opioid receptors and endorphin levels. • Hypertension and chest pain from cocaine or amphetamine use may be treated with nitroglycerin, labetalol, and/or hydralazine. Propranolol is contraindication secondary to the potential of unopposed alpha-adrenergic stimulation following beta-adrenergic blockade. • Treatment of alcohol withdrawal includes benzodiazepines and alpha-2 agonists such as clonidine. • A resuscitation cart should be placed adjacent to the operating room.

FOLLOW-UP • In the postpartum period, the patient should be monitored for signs of substance withdrawal. Appropriate therapy with antihypertensive agents, benzodiazepines, and alpha2 agonists may be required. • The neonate is monitored closely in the neonatal intensive care unit for symptoms of withdrawal.

REFERENCES

1. Howell EM, Heiser N, Harrington M. A review of recent findings on substance abuse treatment for pregnant women. J Subst Abuse Treat. 1999;16(3):195–219. 2. Keegan J, Parva M, Finnegan M, et al. Addiction in pregnancy. J Addict Dis. 2010;29(2):175–191. 3. Kuczkowski KM.Anesthetic implications of drug abuse in pregnancy. J Clin Anesth. 2003;15(5):382–394. 4. Kuczkowski KM.The effects of drug abuse on pregnancy. Curr Opin Obstet Gynecol. 2007;19(6):578–585. 5. Winklbaur B, Jung E, Fischer G. Opioid dependence and pregnancy. Curr Opin Psychiatry. 2008;21(3):255–259. See Also (Topic, Algorithm, Electronic Media Element) • Cocaine abuse • Alcohol abuse

CODES

ICD9

• 648.30 Drug dependence of mother, unspecified as to episode of care or not applicable • 648.40 Mental disorders of mother, unspecified as to episode of care or not applicable • 649.00 Tobacco use disorder complicating pregnancy, childbirth, or the puerperium, unspecified as to episode of care or not applicable ICD10

• O99.320 Drug use complicating pregnancy, unspecified trimester • O99.310 Alcohol use complicating pregnancy, unspecified trimester • O99.330 Smoking (tobacco) complicating pregnancy, unsp trimester

CLINICAL PEARLS

• Substance abuse in the pregnant woman has an unfortunately high incidence. It requires tailoring of the anesthetic management to the needs of the individual high-risk patient. • A preanesthetic plan with nonjudgmental questioning is essential. • Breast-feeding is encouraged in patients on methadone or buprenorphine maintenance. It can potentially decrease NAC severity.

SUPERIOR LARYNGEAL NERVE Peter K. Yi, MD

BASICS DESCRIPTION

• The superior laryngeal nerve (SLN) provides sensory innervation to a portion of the oral pharynx and motor innervation to the cricothyroid muscle, whose primary function is to tense the vocal cords. • The SLN is an important nerve to block in order to achieve adequate anesthesia for instrumentation of the airway (e.g., awake fiberoptic intubation). PHYSIOLOGY PRINCIPLES

• Branch of the vagus nerve • The SLN, itself, is made up of two branches: – Internal: Provides sensation to the base of the tongue, epiglottis, and arytenoids – External: Provides motor innervation solely to the cricothyroid muscle ANATOMY

• The SLN separates from the vagus nerve at the base of the skull and travels along with the internal carotid artery to the superior pole of the thyroid gland (2). • It divides into the internal and external branches at the level of the hyoid bone. • The internal branch of the SLN is usually larger and enters the thyrohyoid membrane before innervating the larynx. • The smaller external branch of the SLN travels along the lateral border of the inferior pharyngeal constrictor muscle. It then descends in an anterior-medial direction and courses along with the superior thyroid artery. As the external branch of the SLN and the superior thyroid artery enter the thyroid capsule, the external branch takes a more medial direction to innervate the cricothyroid muscle. DISEASE/PATHOPHYSIOLOGY

• Because of its sometimes discreet location under the inferior pharyngeal muscle fascia, the external branch of the SLN may be severed during (3) – Thyroid lobectomies – Parathyroidectomies – Anterior approaches to the cervical spine – Neck dissections – Carotid endarterectomies • Since the majority of motor innervation to the vocal cords is by the recurrent laryngeal nerve, damage to the external branch of the SNL does not result in complete vocal cord dysfunction. It could however result in – Decreased voice quality

– Decreased voice strength – Easy tiring – Hoarseness – Possible increased risk for aspiration; the cricothyroid muscle functions to maintain tension and elongation of the vocal cords.

PERIOPERATIVE RELEVANCE

• The SLN provides sensation from the inferior portion of the epiglottis to the vocal cords. Thus, blocking the nerve with local anesthetic agents can be useful for: – Awake fiberoptic intubation – Awake bronchoscopy or esophagoscopy – Transesophageal echocardiography in critically ill patients who cannot be sedated – Treatment or prevention of laryngospasm or stridor especially in the pediatric patient population – Supplement to total IV anesthesia for airway procedures such as rigid bronchoscopy. • SLN block technique (1): – The hyoid bone, located superior to the thyroid cartilage and inferior to the angle of the mandible, is palpated and displaced laterally to identify the greater cornu at each end while the neck is extended (see Figure).

FIGURE 1. Anatomical depiction of superior laryngeal nerve block technique.

– A 25-gauge needle is advanced toward the cornu of the hyoid with one hand, while the other hand applies contralateral pressure at the opposite end. – The needle is advanced until the tip contacts the hyoid bone and then is walked off laterally and posteriorly passing the thyrohyoid membrane to a depth of 1–2 cm.

– The needle is aspirated to ensure that the placement is not intravascular or in the pharynx – 1–3 cc of local anesthetic is injected. The identical procedure is repeated on the other side. • Alternate approach: – Identify the superior ala of the thyroid cartilage and insert the needle toward the superior margin of the cartilage. – The needle is then walked superiorly off the cartilage through the thyrohyoid membrane. – The needle is aspirated and ∼2–3 cc of local anesthetic is injected. This is then repeated on the opposite side. • Risks of SLN blocks (4): – Hypotension and bradycardia have been reported. – Inability to protect the airway and potential for aspiration – Local anesthetic systemic toxicity; small amounts of intravascular injections can readily cause CNS side effects due to the close proximity to the brain. – Edema or airway obstruction if inserted too deeply; insertion into the thyroid cartilage at the level of the vocal cords may cause edema and airway obstruction. – Hematoma formation; maintain pressure should this occur. • Laryngospasm is an exaggeration of the normal glottic closure as a result of stimulation of the vocal cords via the SLN. It is triggered by the presence of blood, secretions, or surgical debris during light anesthesia. It is more common during upper airway procedures and in children. – Manifests initially as stridor and can lead to complete airway obstruction. – Management involves removing the offending stimulus with suctioning, positive pressure ventilation to open the airway, and/or small doses of IV anesthetic or muscle relaxant (typically succinylcholine due to its quick onset and very short duration of action).

REFERENCES

1. Furlan JC. Anatomical study applied to anesthetic block technique of the superior laryngeal nerve. Acta Anaesthesiol Scand. 2002;46(2):199–202. 2. Furlan JC, Brandao LG, Ferraz AR, et al. Surgical anatomy of the extralaryngeal aspect of the superior laryngeal nerve. Arch Otolaryngol Head Neck Surg. 2003;129(1):79–82. 3. Furlan JC, Cordeiro AC, Brandão LG. Study of some “instrinsic risk factors” that can enhance an iatrogenic injury of the external branch of the superior laryngeal nerve. Otolaryngol Head Neck Surg. 2003;128(3):396–400. 4. Wiles JR, Kelly J, Mostafa SM. Hypotension and bradycardia following superior laryngeal nerve block. Br J Anaesth. 1989;63(1):125–127. See Also (Topic, Algorithm, Electronic Media Element) • Recurrent laryngeal nerve • Laryngospasm

CLINICAL PEARLS

• The SLN can also be blocked “noninvasively” – The tongue is retracted and held with gauze.

– A local anesthetic-soaked gauze is placed in a right angle forcep and held at the pyriform sinuses bilaterally for ∼5 minutes. • Unlike partial damage to the recurrent laryngeal nerve (innervation to the single abductor posterior cricoarytenoid), damage to the SLN does not cause airway obstruction and stridor. To that extent, neuromonitoring of the SLN is not routinely performed during surgical procedures. However, damage can be significant to patients who rely on their voice for their occupation. • Damage to the SLN presents as loss of tension of the vocal cord with a wavy appearance on laryngoscopy or bronchoscopy.

SUPPLEMENTAL OXYGEN John J. Freely Jr., MD Christopher A. Skorke

BASICS DESCRIPTION

• The primary goal of oxygen therapy is to prevent or correct hypoxemia and/or tissue hypoxia. • Efficient and rapid oxygen delivery (DO2) is a vital component in the care of critically ill or

injured patients. Certain disease processes including myocardial infarction, acute lung injury, ARDS, pulmonary fibrosis, cardiogenic pulmonary edema, cyanide poisoning, and carbon monoxide inhalation all require supplemental oxygen. • In general, supplemental oxygen is indicated for adults, children, and infants (older than 1 month) when the PaO2 is <60 mm Hg or the SpO2 is <90% while breathing room air. Oxygen therapy is indicated in neonates if the PaO2 is <50 mm Hg, SaO2 <88%, or

capillary PO2 is <40 mm Hg.

• During general anesthesia, supplemental oxygen is required to prevent declines in the PaO2

that can result from decreased functional residual capacity (FRC) and hypoventilation. • The clinical status of the patient and the desired dose of oxygen will determine the choice of the DO2 system. Patients vary considerably in their response to oxygen; additionally, there are several potential hazards associated with its use. Careful monitoring is required to avoid the consequences of hyperoxia.

PHYSIOLOGY PRINCIPLES

• A continuous supply of oxygen is fundamental to normal cellular function and aerobic metabolism. • The transfer of oxygen from alveolar air to pulmonary capillary blood is affected by the PaO2 in the alveoli, its ability to diffuse across the alveolar capillary membrane, and the matching of alveolar ventilation to capillary perfusion. • Delivered oxygen partial pressure (PiO2) is equal to the barometric pressure at one

atmosphere times the fraction of oxygen. At room air it can be calculated as follows: 760 mm Hg × 0.21 = 149.7 mm Hg. At a fraction of inspired oxygen (FiO2) of 1.0, it is

calculated as follows: 760 mm Hg × 1.0 = 760 mm Hg. Upon entering the airway, the gas is humidified and the inspired oxygen tension is reduced by the added water vapor (PH2O is

47 mm Hg at 37°C). Thus it can be calculated as follows: PiO2 = [(Pbaro − PH2O) × FiO2]

• Alveoli. The inspired gases are mixed with residual alveolar gas from previous breaths; oxygen is also taken up and carbon dioxide is added. – Alveolar oxygen tension (PAO2) can be estimated using the alveolar gas equation: PAO2 =

PiO2 – (PaCO2/RQ), where the PaCO2 = arterial CO2 tension and RQ = respiratory quotient. Large increases in PaCO2 (>75 mm Hg) readily produce hypoxia (PaO2 <60

mm Hg) at room air but not at high inspired O2 concentrations.

– The PAO2 can also be quickly estimated in millimeters of mercury (mm Hg) by

multiplying the percentage of inspired O2 concentration by 6. For example at 50%, the

PAO2 is 6 × 50 mm Hg or 300 mm Hg.

• Gradient. The PaO2 in the alveoli for a patient breathing room air (∼100 mm Hg) exceeds that of mixed venous blood (40 mm Hg) and mitochondria (<10 mm Hg). This gradient is the driving force for DO2 from the alveoli to the tissue.

• Adequate tissue oxygenation requires that oxygen content and delivery exceed consumption. Sufficient oxygen content is dependent on normal arterial oxygen tension (PaO2) and

hemoglobin concentration. DO2 to tissues necessitates appropriate blood volume, heart rate,

and cardiac function. Tissue ischemia and hypoxia may occur with circulatory impairment or failure, even if the oxygen content is normal. – Arterial oxygen content (CaO2) is the sum of oxygen dissolved in solution plus that carried by hemoglobin and is expressed by the following equation: CaO2 = 1.34(Hb) (SaO2) +

(0.003) (PaO2), where Hb is the hemoglobin concentration, SaO2 is the arterial

oxyhemoglobin saturation, and PaO2 is the partial pressure of oxygen in arterial blood. Normal CaO2 is ∼20 mL O2/dL.

– DO2 is the amount of oxygen that is transported from the lungs to the microcirculation and is dependent on the cardiac output (Q) and the CaO2. DO2 can be compromised by a

reduction in any component (cardiac output, hemoglobin concentration, or SaO2); however, a decrease in one component may be offset by an increase in another to maintain DO2.

– Oxygen consumption can be calculated indirectly from the Fick equation: VO2 = Q ×

(CaO2–CvO2), where the arteriovenous content difference represents the quantity of O2 extracted by the peripheral tissues. When DO2 is reduced, VO2 usually remains normal

because of increased oxygen extraction (mixed venous O2 saturation decreases); thus VO2 remains independent. With further reductions in DO2, a critical point is reached, beyond

which VO2 becomes directly proportional to DO2. This supply-dependent O2 state typically

is associated with progressive lactic acidosis caused by cellular hypoxia. • Oxygen administration systems are best classified according to their ability to provide adequate flow levels and a range of FiO2. Patient compliance, the presence and type of

artificial airway, and the need for humidification are other considerations in selecting a type of oxygen therapy. • Nasal cannulas provide oxygen into the nasopharynx and it mixes with room air. – Rate: 1–4 L/min

– FiO2: 0.25–0.4; concentration varies depending on the patient’s respiratory rate, tidal

volume, and extent of mouth breathing – Advantages: Comfort and the ability to eat and speak – Disadvantage: Low maximum inspired concentrations of oxygen and the unpredictability of what amount of oxygen is truly being delivered to the patient. Rates >4 L/min can dry the mucous membranes and are discomforting to the patient. – Cautions: Oxygen should be humidified. Flow rates in newborns and children >2 L/min are usually not recommended due to inadvertent administration of positive airway pressure at higher flow rates. • Simple masks fit loosely over the nose and mouth. – Rate: 6–10 L/min – FiO2: 0.3–0.6 – Advantages: Higher oxygen concentrations can be delivered compared to nasal cannula; useful in mouth breathing – Disadvantages: Not precise – Caution: There is some accumulation of CO2 from rebreathing, which may pose a risk in CO2 retainers.

• Partial rebreathing masks consist of a simple mask with a reservoir attached. The term partial refers to the portion of the patient’s expired tidal volume that refills the reservoir bag. – Rate: 10–12 L/min – FiO2: 0.5–0.6

– Advantages: Conserves oxygen supply, particularly during transport – Disadvantages: The lack of a tight seal and valves allows for mixing of room air and the inability to provide an FiO2 of 1.0.

– Cautions: If the oxygen supply is insufficient to prevent collapse of the reservoir, entrainment of room air through the exhalation ports can occur. • Nonrebreathing masks consist of a mask and reservoir modified with two valves. – Rate: 7–15 L/min – FiO2: 0.4–1.0 depending on the flow rate

– Advantages: Exhaled air egresses out of the one way valves, thus allowing for higher fractions of oxygen that can be inspired from the reservoir bag. In spontaneously breathing patients, this technique most reliably supplies the highest oxygen concentration. – Disadvantages: Lacks a tight seal and allows the potential for mixing of room air; cannot provide pressure support or PEEP – Cautions: A key factor to the successful application of this mask is to use a sufficient flow of oxygen so that the reservoir bag is partially filled during inspiration. • Oxygen hoods and tents are enclosure systems primarily used for infants or neonates who require prolonged administration of oxygen. Oxygen hoods are clear plastic cylinders that cover an infant’s head. Oxygen tents are clear plastic shells that cover an infant’s head and upper body. – Rate: Hoods 10–15 L/min; tents >10–15 L

– FiO2: Hoods 0.8–0.9; tents 0.5

– Advantages: More easily tolerated than nasal cannula or masks – Disadvantages: Cannot exactly control FiO2 or deliver positive pressure ventilation

– Cautions: Retinopathy of prematurity (ROP) • Ventilation bags are usually used to provide oxygen and assisted ventilation, either with a mask or through an artificial airway. These are high flow fixed performance systems. – Rate: High flows – FiO2: Close to 1.0

– Advantages: Useful for transport of intubated and mechanically ventilated patients. Face mask positive pressure ventilation can potentially prevent intubation in some situations. – Disadvantages: Cannot measure pressures that are being delivered. Positive pressure ventilation via a face mask may result in stomach insufflation and does not protect the airway from aspiration.

ANATOMY

• Oxygen is carried in the blood in two forms: Dissolved and combined with hemoglobin. • The oxyhemoglobin dissociation curve describes the relationship between PaO2 and

hemoglobin. • Hemoglobin has the dynamic ability to bind and release oxygen and this capability is modulated by pH, CO2, 2,3-diphosphoglycerate, temperature, and fetal hemoglobin. Under normal physiological circumstances, this promotes oxygen uptake in the pulmonary arteries and unloading into the tissues.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Five possible causes of a reduction in PaO2:

– Low inspired oxygen tension – Alveolar hypoventilation – Diffusion impairment – Ventilation/perfusion (V/Q) mismatching – Shunt • Supplemental oxygen is effective in prolonging the survival of patients with COPD that have a resting PaO2 <60 mm Hg; it also mildly improves a patient’s subjective feelings of

dyspnea. However, hypoventilation is a complication often seen in this patient population who also are chronic CO2 retainers. These patients are somewhat dependent on a relative

hypoxemia, due to an altered respiratory drive. In addition, oxygen-mediated release of hypoxic vasoconstriction can result in greater blood flow to areas that are poorly ventilated, worsening the shunt. Elevation of arterial oxygen tension to relatively normal levels can cause severe hypoventilation in these patients. • Absorption atelectasis can occur in patients on oxygen therapy. High concentrations of oxygen in poorly ventilated alveoli are prone to atelectasis when nitrogen (which serves as an alveolar “filler") is washed out of the lungs. The pulmonary capillaries readily take up alveolar oxygen (uptake greater than intake), leading to alveolar collapse.

• Oxygen toxicity. Lung damage can occur with prolonged high concentrations of oxygen. Toxicity is dependent on both the inspired PaO2 and the length of exposure. The alveolar

oxygen tension rather than the arterial oxygen tension is more important in the development of lung toxicity. Generally speaking, 100% oxygen for <24 hours is considered safe, but concentrations >50% for prolonged periods of time are undesirable as they may lead to toxicity. Oxygen toxicity is believed to be due to intracellular generation of highly reactive oxygen metabolites or free radicals. These metabolites are cytotoxic because they readily react with cellular DNA, sulfhydryl proteins, and lipids. The injury to the lung is indistinguishable from ARDS. Pulmonary capillary membrane permeability increases, and the membrane is thickened secondary to proliferation of type II alveolar cells. Pulmonary O2 toxicity in newborn infants is manifested as bronchopulmonary dysplasia.

• ROP is a neovascular retinal disorder that is common in premature infants. Initially, the hyperoxic stage impairs normal vascularization of the retina. The retina is particularly sensitive to this effect, because of the high rate of blood flow to the choroidal circulation. The hypoxic stage follows and is the result of high oxygen requirements by the retinal vasculature being unmet. As a result, hypoxia-inducible factor and vascular endothelial growth factor are consequently released. These factors result in “neovascularization" with abnormal proliferation from the retina to the vitreous. Neovascularization can cause fluid leak, hemorrhage, and retinal scar formation with traction of the retina. In severe cases, traction can lead to detachment and blindness. • Oxygen is highly combustible and has the potential to cause fires and explosions. Caution must be taken when the fire triad (ignition source, oxidizer, fuel) can develop (e.g., sedation cases with supplemental oxygen for procedures above the xiphoid that use electrosurgical instruments).

PERIOPERATIVE RELEVANCE

• The concept of O2 stores is vital in anesthesia. During apnea, the vital flux of O2 is

interrupted, and existing stores of O2 are consumed by cellular metabolism. When these

stores are depleted, hypoxia and subsequent cell death follow. • Normal O2 stores are limited to what is present in the lungs (FRC), bound to hemoglobin, and dissolved in blood. To that extent, the oxygen contained within the FRC is the main O2 store. Following ventilation with 100% O2, FRC contains a much greater content of O2 as

compared to a patient breathing room air. This increase in O2 stores delays hypoxemia

following apnea and ultimately forms the basis for preoxygenation (or denitrogenation) prior to induction of anesthesia.

EQUATIONS

• PiO2 = (Pbaro – PH2O) × FiO2; where PiO2 is the partial pressure of oxygen that after mixing with water vapor, Pbaro is the atmospheric pressure, PH2O is the partial pressure of water vapor found in the airway, and FiO2 is the fraction of inspired oxygen.

• PAO2 = PiO2 – [PaCO2/RQ]; where PAO2 is the partial pressure of oxygen in the alveoli,

PaCO2 is the partial pressure of carbon dioxide in the artery, and RQ is the respiratory

quotient. • CaO2 = 1.34(Hb)(SaO2) + (0.003/PaCO2); where CaO2 is the oxygen content in the

arteries, Hb is hemoglobin, SaO2 is the arterial oxygen saturation, and 0.003 is oxygen’s

solubility coefficient. • DO2 = Q × CaO2; where DO2 is the oxygen delivery to organs/tissue, Q is the cardiac output. • VO2 = Q × (CaO2 – CvO2); where VO2 is the oxygen consumption by tissues, CvO2 is the oxygen content in the veins.

REFERENCES

1. Bateman NT, Leach RM. ABC of oxygen. Acute oxygen therapy. BMJ. 1998;317:798. 2. Bradley JM, Lasserson T, Elborn S, et al. A systematic review of randomized controlled trials examining the short-term benefit of ambulatory oxygen in COPD. Chest. 2007;131:278. 3. Durrington HJ, Flubacher M, Ramsay CF, et al. Initial oxygen management in patients with an exacerbation of chronic obstructive pulmonary disease. QJM. 2005;98:499. 4. Jensen AG, Johnson A, Sandstedt S. Rebreathing during oxygen treatment with face mask. The effect of oxygen flow rates on ventilation. Acta Anaesthesiol Scand. 1991;35:289. 5. Myers TR. American Association for Respiratory Care (AARC). AARC Clinical Practice Guideline: Selection of an oxygen delivery device for neonatal and pediatric patients— 2002 revision and update. Respir Care. 2002;47:707. 6. Stoller JK, Panos RJ, Krachman S, et al. Oxygen therapy for patients with COPD: Current evidence and the long term oxygen treatment trial. Chest. 2010;138:179. 7. SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Carlo WA, Finer NN, et al. Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med. 2010;362:1959. 8. Tanni SE, Vale SA, Lopes PS, et al. Influence of oxygen delivery system on the quality of life of patients with chronic hypoxemia. J Bras Pneumol. 2007;33:161. 9. Vallet B. Perioperative oxygen therapy and oxygen utilization. Curr Opin Crit Care. 2010;16:359–364. See Also (Topic, Algorithm, Electronic Media Element) • Oxygen toxicity • Partial pressures

CLINICAL PEARLS

• Supplemental oxygen is often utilized perioperatively to avoid the harmful effects of hypoxemia in the setting of benzodiazepines, opioids, residual volatile agents, or neuromuscular blocking agents.

• It is important to assess the need as well as the characteristics of each DO2 system.

SUPRACELIAC/SUPRARENAL AAA REPAIR Ali R. Abdullah, MBChB Ibetsam Hilmi, MBChB, FRCA

BASICS DESCRIPTION General

• An aneurysm is defined as a permanent dilation of a blood vessel that is at least 1.5 times the diameter of the expected normal value; it can be fusiform or saccular in morphology. • Abdominal aortic aneurysms (AAAs) can be either above the renal arteries (suprarenal) or below (infrarenal). Compared to infrarenal AAA repair, suprarenal repair is associated with greater: – Hemodynamic effects – Blood loss – Risk of spinal injury – Renal insufficiency – Conversion to open repair from endovascular • Following dissection and exposure of the aneurysm, the patient is heparinized. Crossclamping of the aorta is performed distal to the aneurysm, followed by clamping of the aorta above the renal arteries. Once the graft is sutured into place, the proximal and distal suture lines are examined for bleeding. • Heparin reversal may be performed after discussion with the surgeon; protamine 1mg for every 100 U of heparin. • While open repair is still indicated in certain cases (e.g., lack of an adequate implantation site for the stent), endovascular repair is commonly performed. Open repair is associated with – Increased 30-day mortality – Increased morbidity: Longer hospital stay and postoperative pulmonary, cardiac, and renal complications – Increased blood transfusion requirement – Increased analgesia requirement Position/Incision

Supine with upper abdominal incision Approximate Time

• <6 hours • Cross-clamping may last for 30–60 minutes

EBL Expected • >250 mL

• Common surgical complications – bleeding, coagulopathy, prolonged cross-clamp time, and visceral injuries

Hospital Stay

• 5–10 days for open repair • Ruptured aneurysms may require a longer hospital stay.

Special Equipment for Surgery • Cell salvage • Rapid infuser

EPIDEMIOLOGY Prevalence

• AAA is present in 5.9 per 100,000 people. • Increased incidence with age due to exposure to risk factors and decreased aorta compliance. • In the US, AAAs are more common in white males than black males.

Prevalence

• <1% in the population under 50 years old. • By the 7th decade of life, prevalence >5%

Morbidity

Acute rupture, paraplegia, postoperative sepsis, respiratory failure, renal dysfunction, MI, and heart failure. Mortality

Male/female mortality ratio 4/5

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patient population often with multiple comorbidities that require concurrent management in the perioperative period. • Anticipate large hemodynamic swings and optimize changes in blood pressure and tachycardia to maintain perfusion to vital organs. • Implement measures to protect renal function. • Spinal cord protection may involve distal aortic perfusion, CSF drainage, and systemic/local hypothermia.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Often asymptomatic. • Abdominal pain is a common complaint. • Acute rupture can present with severe, sudden abdominal pain, and/or hemorrhagic shock.

History

• Detect any coexisting disease; risk factors include smoking, hypertension, hyperlipidemia, family history, age, and diabetes mellitus. • Etiology includes atherosclerosis (90%), hereditary disorders (e.g., Marfan’s), traumatic, inflammatory, or as a sequelae of chronic aortic dissections. Signs/Physical Exam

HTN, tenderness in abdomen or lower back, throbbing mass in abdomen, audible thrill in abdomen on auscultation. MEDICATIONS

Beta-blockers. By decreasing BP and heart rate, they are effective in reducing the sheer force on the aortic wall and may reduce the incidence of aneurysmal rupture. Additionally, initiation prior to major vascular surgery may reduce morbidity and mortality; optimal dose, particular drug, duration of time, and target heart rate have not been elucidated. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, renal panel, Hg, coagulation studies. • Abdominal US/CT scan for diagnosis and monitoring of size. • Cardiac evaluation: EKG; stress testing. A coronary angiography may be performed for high risk patients or a stress test that suggests ischemia. CONCOMITANT ORGAN DYSFUNCTION

Peripheral vascular disease, coronary artery disease, renal insufficiency, COPD, diabetes mellitus, morbid obesity, transient ischemic attacks, or previous cerebrovascular events.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Beta-blockers; titrate to heart rate • Anxiolytics, and analgesia • Initiation of statins

Special Concerns for Informed Consent

• Blood consent • Potential for postoperative intubation, spinal cord injury, myocardial events • Epidural catheter consent if no contraindications to placement. Traumatic placement may necessitate delaying the procedure (intraoperative heparin)

Antibiotics/Common Organisms

Cefazolin 1–2 g IV; if cephalosporin allergy, any other broad- spectrum antibiotic

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia • Epidural catheter placement for open procedures if coagulation studies are within acceptable limits and antiplatelet therapy does not contraindicate. Consider a paraverterbral block in the presence of an INR >1.5.

Monitors

• Standard ASA monitors • Two large bore IVs • Arterial line; consider preinduction placement • Central venous catheter for CVP monitoring and venous access • Pulmonary artery catheter and transesophageal echocardiography (TEE) if comorbidities warrant • Foley catheter • Motor-evoked potentials (MEPs) to assess anterior spinal cord perfusion • BIS to monitor depth of anesthesia

Induction/Airway Management

• A slow, controlled induction should be performed to ensure an adequate depth of anesthesia and minimize hypertensive and tachycardic responses during laryngoscopy and intubation – Choose quick onset/offset agents (e.g., esmolol, nitroglycerine) – In patients at risk for pulmonary aspiration, carefully weigh the risks versus benefits of a rapid sequence induction (HTN, tachycardia) • Muscle relaxation. Baseline MEPs are usually attained after induction. If needed and not contraindicated, succinylcholine should be utilized. Alternatively, short duration nondepolarizing agents may be needed but should be communicated and discussed with the surgeon and neuromonitoring team • Epidural analgesia is advantageous for postoperative pain; it is often prudent to wait until after the aorta is unclamped and hemodynamics has stabilized to bolus the epidural and begin an infusion.

Maintenance

• Balanced anesthetic with volatile agent or IV techniques; avoid muscle relaxants if MEPs are measured. • Cross-clamping: – Preload: Increased secondary to venous redistribution. – Afterload: Increased by the clamp; more profound than with infrarenal clamps. Compensatory vasodilation occurs above the clamp. May be poorly tolerated in patients with left ventricular dysfunction (increased tension/myocardial oxygen consumption). Myocardial ischemia and left ventricular failure can result if not properly anticipated. Treat aggressively with vasodilators (nitroprusside, nicardipine, propofol). – Heart rate: Reflex bradycardia may be seen. – Contractility will increase in a normal heart; patients with cardiac disease may not be able

to compensate. – SVR: Increases distal to the clamp to maintain perfusion; vasodilators can impair distal perfusion pressure. • Unclamping of the aorta: Release and activation of a wide range of bioactive mediators (e.g., proinflammatory cytokines, nitric oxide) leads to systemic vasodilatation with relative hypovolemia and myocardial depression. – Preload: Decreases as vasodilated arterial beds fill with blood; volume loading should be performed prior to unclamping. – Afterload is abruptly decreased. Consider initiating phenylephrine or norepinephrine drip a few minutes prior to anticipated release of cross clamp or bolusing, as needed. – Contractility: Washout of metabolites from lower extremity ischemia may impair inotropy and necessitate the use of inotropes. – Pulmonary artery pressure can increase from hypercarbia, acidosis, and ischemic metabolites. – Frequent ABG testing should be performed to diagnose and treat lactic acidosis from splanchnic hypoperfusion, hypocalcemia, or other electrolyte imbalances. • Spinal cord ischemia can result from interruption to its blood supply secondary to a variable and unpredictable anatomy of the collateral intercostal and lumbar arteries (especially the artery of Adamkiewicz). – Lumbar CSF drains are placed preoperatively. Drainage of CSF can increase cord perfusion (dependent on mean arterial pressure minus CSF pressure/venous pressure in the epidural veins). – Methylprednisolone 30 mg/kg before and after aortic occlusion may result in improved spinal cord protection. – Minimize clamp time to <30 minutes. – Lower limb MEPs provide indirect monitoring of compromised cord perfusion. – Other strategies: Maintain a high systemic arterial pressure, low systemic venous pressure, and adequate right heart venous return; correct acidosis; and avoid hypoxia. • Coagulopathy. Can cause, (or result from), excessive surgical bleeding, intraoperative heparin, or multiple transfused cell salvage units (washing and processing depletes coagulation factors). • Renal protection. Adequate hemodynamics, volume, and inotropy. Mannitol 0.5 g/kg prior to cross clamping, sodium bicarbonate infusions, and fenoldapam/dopamine may be used, but their efficacy is controversial.

Extubation/Emergence

• Avoid sympathetic stimulation during extubation/emergence. • Continue antihypertensive medications during extubation/emergence and ensure adequate analgesia prior to extubation; if an epidural catheter is in place and the patient is hemodynamically stable, the infusion may be started. • Neurological function should be assessed as soon as possible.

FOLLOW-UP

BED ACUITY ICU

ANALGESIA

• Maybe difficult to titrate in the intubated ICU patient. • Continue regional anesthesia in the postoperative period and only remove if no signs of coagulopathy are present (check the TEG and/or INR, PTT and platelet count)

COMPLICATIONS

• Hypotension could be a sign of intraabdominal or retroperitoneal bleeding. • Postoperative care may be complicated by the presence of comorbidities such as CAD, COPD, and CRF. • Complications include MI, neurological deficits, spinal cord ischemia, renal failure, sepsis, respiratory failure, and ventilator dependency.

REFERENCES

1. Blanchard JF. Epidemiology of abdominal aortic aneurysms. Epidemiol Rev. 1999;21(2):207–221. 2. Chang CK, Chuter TA, Reilly LM, et al. Spinal arterial anatomy and risk factors for lower extremity weakness following endovascular thoracoabdominal aortic aneurysm repair with branched stent-grafts. J Endovasc Ther. 2008;15(3):356–362. 3. DREAM Study Group. Long-term outcome of endovascular repair of abdominal aortic aneurysm. NEJM. 2010;362:1881–1889. 4. El-Sabrout RA, Reul GJ. Suprarenal or supraceliac aortic clamping. Tex Heart Inst J. 2001;28:254–264. 5. Jacobs MJ, Mess W, Mochtar B, et al. Spinal cord blood supply in patients with thoracoabdominal aortic aneurysms. J Vasc Surg. 2002;35(1):30–37. 6. Jean-Claude JM, Reilly LM, Stoney RJ, et al. Pararenal aortic aneurysms: The future of open aortic aneurysm repair. J Vasc Surg. 1999;29:902–912. 7. Kahn RA, Stone ME, Moskowitz DM. Anesthetic consideration for descending thoracic aortic aneurysm repair. Semin Cardiothorac Vasc Anesth. 2007;11:205. See Also (Topic, Algorithm, Electronic Media Element)

• Abdominal aortic aneurysm • Somatosensory and motor-evoked potentials • Postoperative renal dysfunction • Endovascular aneurysm repair (EVAR) • Somatosensory and motor evoked potentials (SSEPs/MEPs)

CODES ICD9

441.4 Abdominal aneurysm without mention of rupture ICD10 I71.4 Abdominal aortic aneurysm, without rupture

CLINICAL PEARLS

Preserve myocardial, pulmonary, renal, and CNS perfusion. Postoperative renal failure ranges form 12–31% and is the most common factor seen in early mortality.

SUPRAGLOTTIC DEVICES Jennifer Wu, MD, MBA

BASICS DESCRIPTION

• Supraglottic devices are blind-insertion airway support devices that sit above the glottis. They – Allow for spontaneous and/or limited positive pressure ventilation – Are used as planned or rescue airway devices – Are available mostly as disposable devices – Are generally latex free • Commonly utilized devices on the market include the – Laryngeal mask airway (LMA) – Combitube – King LT-D/LTS-D (suction capability) PHYSIOLOGY PRINCIPLES

• Indications: Supraglottic devices are appropriate when mask ventilation is desired but endotracheal intubation is not necessary. • Advantages: – Compared to mask ventilation, it is more secure, allows “hands-free" ventilation, and decreases spillage of volatile agents into the operating room. – Avoidance of laryngoscopy (and muscle relaxation) – Avoidance of tracheal stimulation in cases where general anesthesia is desired (e.g., reactive airway disease). – Decreased postoperative sore throat – Part of the difficult airway algorithm (2). May facilitate ventilation in patients that cannot be ventilated with a mask. Additionally, it can serve as a conduit for tracheal intubation, especially in a difficult airway situation. An endotracheal tube, tube exchanger, Aintree, or fiberoptic bronchoscope can also be passed, depending on the device. • Placement: Following induction, the device is inserted blindly into the pharynx and rests above the vocal cords. The apertures are positioned to deliver fresh gas flow directly over the laryngeal inlet. • LMA – Four main components: Soft cuff, airway tube, inflation balloon, and connector – The cuff is designed to conform to the contours of the hypopharynx with its lumen facing the laryngeal opening. – The airway tube has a single large-bore lumen; an appropriately sized endotracheal tube can be passed through it. – Sizing varies by manufacturer and is usually weight based. – Used in the difficult airway algorithm in a “cannot intubate, cannot ventilate” situation.

• Combitube (1) – Four main components: Two cuffs, double lumen, two inflation balloons, and two possible connections – The distal cuff is low volume and can hold up to 15 mL of air; the proximal cuff is larger and can hold up to 85 mL of air. They are designed to seal the upper airway and isolate the trachea from the esophagus. – It is inserted blindly and the distal cuff enters either the trachea or esophagus; the lumen used for ventilation depends on the location in which it was placed. – If the distal cuff is inserted in the trachea, then the distal lumen delivers air directly into trachea. If the distal cuff is inserted into the esophagus, multiple apertures located in between the distal and proximal cuff serve to deliver air over the laryngeal inlet. – Only available in adult sizes 37 Fr and 41 Fr; cannot be used in the pediatric population. • King LT-D/LTS-D – Four main components: Two cuffs, single lumen tube, a single inflation balloon, and connector – It is inserted blindly, with the lumen entering the esophagus (size and angle favor posterior passage). The two cuffs (one for the oropharynx and the other for the esophagus) are inflated simultaneously; the cuffs are high volume and low pressure. – Multiple ventilation holes are located between the cuffs; they are positioned to deliver air over the laryngeal inlet. – The single lumen allows passage of a bronchoscope or tube exchanger to emerge through a “ramp” in the pharyngeal cuff that is directly over the laryngeal inlet. This allows for tube exchange or examination. – The King LTS-D has a double lumen/side port that allows passage of suction, a tube exchanger, or a fiberoptic scope that would emerge at the distal end (esophagus) and would not disrupt ventilation. – Sizing is based on height ANATOMY

• LMA – The cuff area should be lubricated with plain jelly to reduce friction against the hard palate. The use of lidocaine jelly may cause postoperative numbness that distresses patients. – The cuff can be fully, partially, or not inflated during insertion. – Insertion is commonly performed with the head extended using the dominant hand. – The cuff is pressed upward toward the hard palate. – Care should be taken not to “drag” the tongue; this may be achieved by displacing the tongue from the hard palate with fingers from the nondominant hand (or providing a chin lift), a tongue depressor, or even a laryngoscope. – The LMA should be advanced past the epiglottis; final position should be in the hypopharynx above the vocal cords. The ventilation outlet is midline, directly over the glottic opening. – A “good fit” is confirmed by assessing tidal volumes and the pressure where a leak is detectable. – Removal may be performed with the cuff fully, partially, or not inflated. Some advocate

not deflating in order to “pull out” secretions

FIGURE 1. Laryngeal mask airway. Single-lumen, single-cuff, single-balloon inflation

• Combitube (1) – Insertion should occur with the cuffs deflated and lubricated with plain jelly. – Using the dominant hand, the device is placed blindly and gently, without force, to a depth where the upper incisors are between the two black lines on the device. The tongue should not be “dragged;” consider above-mentioned techniques as appropriate. – The distal cuff is inflated with 10–12 mL and ventilation is performed via the distal connector while listening for gurgling sounds over the epigastrium or bilateral breath sounds over the lungs. – If breath sounds over the lungs are heard, the tube has entered the trachea; the distal cuff should remain inflated and ventilation is performed via the distal lumen, as with a standard endotracheal tube. – More commonly, gurgling sounds are heard over the epigastrium, indicating that the tube has entered the esophagus. Inflate both cuffs to prevent air from escaping through the esophagus or back out the oropharynx/nasopharynx. Ventilate via the proximal lumen. Fresh gas flow is delivered through the multiple apertures situated above the distal cuff.

FIGURE 2. Combitube. Double-lumen, double-cuff, double-balloon inflation

• King LT-D

– Insertion should occur with the cuffs deflated and lubricated with plain jelly. – The device is inserted blindly with the dominant hand into the esophagus until the upper incisors are between the black lines on the device. The nondominant hand is used to hold the mouth open and apply a chin lift as needed. Some advocate for introduction using a lateral approach, followed by rotation back to midline once the tip is behind the base of the tongue – The distal cuff inflates in the esophagus and the proximal cuff inflates at the base of the tongue. – It may be necessary to gently pull back while assessing ease of ventilation and tidal volumes. Readvancement cannot be performed with the cuffs inflated. – To utilize the gastric lumen in the King LTS-D, the suction catheter needs to be lubricated.

FIGURE 3. King LT-D. Single-lumen, double-cuff, single-balloon inflation

DISEASE/PATHOPHYSIOLOGY

• Relative contraindications for supraglottic devices include – Risk of aspiration: Because these devices sit above the vocal cords and do not isolate the trachea from the esophagus, patients are not protected from aspiration. Endotracheal intubation is preferable for patients who are pregnant or in patients at risk for aspiration. – Major abdominal or thoracic surgery – When high-inspiratory pressures are required for ventilation: Supraglottic devices are not ideal for laparoscopic procedures or Trendelenburg position because it may be difficult to administer adequate positive pressure ventilation. Additionally, decreased respiratory system compliance can be seen in patients with obesity and restrictive pulmonary disease. – Patient positioning influences the seating and seal. Supraglottic devices should not be used for cases in the prone position. Leak and cuff pressures are altered in the LMA with changes in head extension and mouth opening. • Potential difficulties: – “Poor seating” or malpositioning, resulting in poor seal and large leak. – Dental trauma – Bleeding – Sore throat. – Hiccups – Vagal response • Laryngospasm: Because supraglottic devices sit above the vocal cords, they do not protect against laryngospasm. Laryngospasm can occur at any time when there is an inadequate

depth of anesthesia.

PERIOPERATIVE RELEVANCE

• Because the trachea is not manipulated, the use of a supraglottic device makes bronchospasm and coughing on emergence less likely. The sympathetic stimulation with direct laryngoscopy is also avoided. • General anesthesia must be induced before insertion, but laryngoscopy and muscle relaxation are not necessary. • Patient is able to breathe spontaneously, through a wider lumen than an endotracheal tube. • In addition to being used electively, they are also part of the difficult airway algorithm (2). When laryngoscopy fails and ventilation is not effective, an LMA (or other supraglottic device) can be placed blindly. • The amount of air to be placed in the supraglottic device and the optimal cuff pressure are controversial. Placing the amount of air recommended by the manufacturer may avoid overinflation and excessive cuff pressures. • Some devices include a built-in bite block. Otherwise, a prepared bite block or gauze may be used to prevent biting down. • Some devices include a port for nasogastric tube placement. Otherwise, placement of such a tube may be difficult or impossible without compromising the seal. • The LMA is useful to assist with intubation. With the LMA-Aintree technique, an LMA is placed and ventilation is confirmed (3). An Aintree Intubation Catheter (AIC) is fiberoptically guided through the LMA into the trachea. The LMA and fiberoptic scope are removed while the AIC is left in place. The endotracheal tube is passed over the AIC and the AIC is removed.

REFERENCE

1. Urtubia RM, Aguila CM, Cumsille MA. Combitube: A study for proper use. Anesth Analg. 2000;90:958–962. 2. Practice guidelines for management of the difficult airway: An updated report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology. 2003;98: 1269–1277. 3. Turk M, Gravenstein D (2007). Aintree Intubation Catheter Technique in Unanticipated Difficult Intubation. Retrieved March 10, 2011 from University of Florida Department of Anesthesiology, Center for Simulation, Advanced Learning and Technology, Virtual Anesthesia Machine Web site: http://vam.anest.ufl.edu/ airwaydevice/aintree/index.html.

4. Bein B, Scholz J. Supraglottic airway devices. Best Practice & Research Clinical Anaesthesiology. 2005;19(4):581–593.

See Also (Topic, Algorithm, Electronic Media Element) • Difficult airway • Laryngospasm

CLINICAL PEARLS

• Supraglottic devices are useful in “cannot intubate, cannot ventilate” situations. • They do not protect the trachea from aspiration of gastric contents or laryngospasm (4). • The Combitube has an increased incidence of sore throat, dysphagia, and upper airway hematoma when compared to LMAs and endotracheal tube. Esophageal rupture is a rare complication that has been reported, thus known esophageal disease is a contraindication.

SURGICAL SITE INFECTIONS, PREVENTION Edward C. Nemergut, MD

BASICS DESCRIPTION

A surgical site infection (SSI) is a bacterial infection of the skin or underlying tissue that results from a surgical wound. This definition was established in 1992 when the Centers for Disease Control (CDC) revised its definition of “wound infection” to prevent confusion between the infection of a surgical incision and the infection of a traumatic wound. EPIDEMIOLOGY Prevalence

• The overall incidence of SSI is ∼3%; however, the incidence varies greatly for each operative procedure, surgeon, hospital, and country. • Depending upon the series, SSIs are the second or third most common nosocomial infection after urinary tract infections and lower respiratory infections, respectively. • “Contaminated” procedures are typically associated with the highest incidence of infection. In the CDC’s Study on the Effect of Nosocomial Infection Control (SENIC), the wound infection risk in patients undergoing colon surgery ranged from 9% to 27% • “Clean” procedures are typically associated with a lower incidence of infection. • In the US, there are ∼500,000 SSIs each year.

Morbidity

• Highly dependent on the site of infection and the depth of the tissues infected. For example, deep sternal wound infection after cardiac surgery is associated with high morbidity; whereas skin infection after a superficial lipoma resection is associated with lower morbidity. Nevertheless, most SSIs are superficial, but contribute greatly to the morbidity and mortality associated with surgery. • In the US, mean estimates of prolonged hospitalization vary from 5 to 20 days per infection. A review of the incidence and economic burden of SSIs in Europe estimated that the mean length of extended stay attributable to SSIs was 9.8 days. • SSI also leads to a longer ICU stay and a five-fold increase in the need for hospital readmission. • Costs are higher after discharge because many patients recovering from wound infections are usually discharged before the wound closes entirely, and thus require dressing changes and home nursing visits. Patients may also require long-term IV antibiotics and the consequent need for central line access. Mortality

Like morbidity, mortality is highly dependent on the site of infection and the depth of the tissues infected. For example, the mortality associated with deep sternal wound infection after

cardiac surgery ranges from 6% to 30%, with a mean around 13%. ETIOLOGY/RISK FACTORS

• Type of surgery • Character and magnitude of bacterial contamination • Hypothermia • Hyperglycemia • The presence of foreign bodies in the wound • Hypovolemia • Patient immune function or immunosuppression • Blood transfusion • Inappropriate or inadaquate antimicrobial prophylaxis • The National Nosocomial Infection Surveillance System (NNISS) can help quantify risk based on the type of surgery, American Society of Anesthesiologists’ physical status rating, and surgical duration.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Wound contamination – Even with perfect surgical technique, clean surgical wounds will inevitability become contaminated with bacteria. The ability of a patient to prevent contamination from becoming an infection is dependent on an intact immune response. The first few hours after surgery represent the critical period; wherein the course from contamination to infection is either blunted or progresses (even if the infection may not manifest for several days). • Immune response – The body’s first line of defense against bacterial pathogens is nonspecific killing by neutrophils, an oxygen-dependent process. Oxidative killing depends on the production of the bactericidal superoxide radical from molecular oxygen, catalyzed by the enzyme NADPH oxygenase. It is not surprising that the risk of infection is related to the oxygen tension in the wound and infection. In one study, tissue oxygen measured in the patient’s upper arm only 75 minutes after colorectal surgery predicted development of postoperative SSI, although infections were typically diagnosed more than a week later. • Optimization – The prevention of infection revolves around optimizing wound physiology. Adequate tissue perfusion provides ample oxygen substrate and neutrophils. – In order to be effective, antibiotics must be present in the skin and subcutaneous tissues at adequate concentrations prior to surgical incision.

PREVENTATIVE MEASURES

• The Surgical Care Improvement Project (SCIP) partnership is a multi-year national campaign in the US focused on substantially reducing surgical mortality and morbidity, including the incidence of SSIs. Some recommendations are more applicable to surgeons (e.g., appropriate hair removal), whereas others are more applicable to anaesthetists. • Appropriate timing and selection of antibiotics – Timely administration of antibiotics is necessary for effective infection prophylaxis so that

adequate tissue concentrations are present at the time of surgical incision. Most recommendations suggest that IV antibiotics should be administered between 15 and 60 minutes prior to incision. – It is also important to select antibiotics that cover the bacteria most likely to cause infection in a given procedure. In general, a first-generation cephalosporin (e.g., cefazolin) is appropriate for most clean procedures. For contaminated procedures, a secondgeneration cephalosporin (e.g., cefoxitin) may be appropriate. Beta-lactam allergic patients require special considerations. – As anaesthetists are typically responsible for the administration of antibiotics, they should be familiar with all current guidelines. • Optimize wound physiology. Adequate tissue perfusion provides ample oxygen substrate and neutrophils. • Maintenance of normothermia (>36°C) – In a 1996 study of patients undergoing colorectal surgery, patients randomized to hypothermia were three times more likely to develop a SSI compared to patients randomized to normothermia. Additionally, the duration of hospitalization was prolonged by 2.6 days in the hypothermia group. • Control of hyperglycemia – In patients undergoing cardiac surgery, perioperative hyperglycemia is strongly associated with SSIs. That said, the risks of aggressive glucose control must be measured against the significant risks associated with hypoglycemia. Recommendations may be patient-specific and disease-specific; however, most data suggests that glucose should be controlled with an IV insulin infusion to keep levels below 180 mg/dL. • Hyperoxia – The use of normobaric hyperoxia (∼80%) has been shown to decrease the risk of SSI during surgery and the immediate postoperative period. Of note, in all trials demonstrating efficacy, hyperoxia was continued for a minimum of 2 hours after the conclusion of surgery. – It is unknown if normobaric hyperoxia used only during the intraoperative period is associated with decreases in the risk of SSI. A meta-analysis of the results found it reasonable to conclude that hyperoxia has a beneficial, albeit limited, effect on the incidence of SSI.

PREOPERATIVE ASSESSMENT • CDC criteria, revised in 1992, for incisional SSI are an infection at the incision site within 30 days after surgery as defined by any of the following items: – Purulent drainage from the incision or drain located above the fascial layer – Organism isolated from a fluid culture in a closed wound – Surgeon deliberately opens wound (unless the wound culture is negative) – Surgeon’s or attending physician’s diagnosis of infection • The CDC criteria for deep surgical wound infections are an infection related to surgery occurring at the operative site within 30 days of surgery involving tissues or spaces at or beneath the fascial layer and any of the following:

– Purulent drainage from the drain placed beneath the fascial layer – Wound spontaneously dehisces or is deliberately opened by the surgeon when the patient has a fever (>38°C) and/or localized pain or tenderness, unless the wound culture is negative – An abscess or other evidence of infection seen on direct examination, during surgery, or by histopathologic examination – Surgeon’s diagnosis of infection

TREATMENT SSIs are typically treated with a combination of antibiotic and/or surgical drainage.

FOLLOW-UP • Scheduled antibiotics are often necessary • Return to the operating room for a “wash out” in certain incidences.

REFERENCES

1. Haley RW, Culver DH, Morgan WM, et al. Identifying patients at high risk of surgical wound infection. A simple multivariate index of patient susceptibility and wound contamination. Am J Epidemiol. 1985;121(2):206–215. 2. Houbiers JG, et al. Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal surgery: A prospective study. Transfusion. 1997;37(2):126–134. 3. Jonsson K, Jensen JA, Goodson WH III, et al. Assessment of perfusion in postoperative patients using tissue oxygen measurements. Br J Surg. 1987;74(4):263–267. 4. Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of wound infection and temperature group. N Engl J Med. 1996;334(19):1209–1215. 5. Mauermann WJ, Nemergut EC. The anesthesiologist’s role in the prevention of surgical site infections. Anesthesiology. 2006;105(2): 413–421. 6. Mauermann WJ, Sampathkumar P, Thompson RL. Sternal wound infections. Best Prac Res Clin Anaesthesiol. 2008;22(3):423–436. 7. Murray BW, Huerta S, Dineen S, et al. Surgical site infection in colorectal surgery: A review of the nonpharmacologic tools of prevention. J Am Coll Surg. 2010;211(6):812–822. 8. Nichols RL. Preventing surgical site infections: A surgeon’s perspective. Emerg Infect Dis. 2001;7(2): 220–224. See Also (Topic, Algorithm, Electronic Media Element) • Hypothermia • Hyperglycemia

CODES ICD9

998.59 Other postoperative infection ICD10 • T81.4XXA Infection following a procedure, initial encounter • T81.4XXD Infection following a procedure, subsequent encounter • T81.4XXS Infection following a procedure, sequela

CLINICAL PEARLS

• Although generally thought to be a surgical complication, the incidence of SSIs is lower when anaesthetists take an active role in infection prevention. Studies have shown that when anaesthetists administer antibiotics, on time administration occurs 92% of the time. • Keep patients warm. • Check and control blood glucose in patients prone to hyperglycemia. • Consider normobaric hyperoxia if there is no contraindication.

SYNCHRONIZED ELECTRICAL CARDIOVERSION Susan Kaplan, MD

BASICS DESCRIPTION General

• Synchronized electrical cardioversion is the delivery of a brief pulse of external electrical direct current (DC) across the chest wall to convert certain abnormal rhythms to a normal sinus rhythm (NSR) in elective or emergent scenarios. It is utilized for (1): – Atrial fibrillation (elective treatment is the most common indication). – Reentry supraventricular tachycardia (SVT) – Atrial tachycardia – Monomorphic ventricular tachycardia (VT) with pulses • Elective cardioversion (CVN) is generally performed by a cardiologist or electrophysiologist in a controlled setting. • Urgent or emergent CVN may be performed in the perioperative period by the anaesthetist. • A biphasic, synchronized discharge is delivered via paddles or self-adhesive electrodes (pads or patches). – Current flow is either in the anterolateral (AL) or anteroposterior (AP) direction. – Electrode positioning: Parasternal and inferoapical for AL, parasternal and left infrascapular for AP. – Electrodes should be firmly adherent to chest wall with sufficient conductive gel to prevent skin burns or improper current dispersion. – If a pacemaker or internal cardioverter defibrillator (ICD) is present, electrodes should be positioned 15 cm from the device (2), preferably in the AP position • Energy requirements for DC CVN vary depending on the underlying rhythm (Biphasic mode). – Atrial fibrillation: 120–200 J; if initial shock fails, increase sequentially (200 J then 360 J) (1) – Atrial flutter: 50–100 J (2) – Monomorphic VT with pulse: 100 J; if initial shock fails, increase sequentially (200 J then 360 J) (1) • Synchronization and discharge occur with the R or S wave of the QRS complex to avoid energy delivery during the relative refractory period of the myocardium (apex of T wave) that can result in malignant ventricular arrhythmias • Common surgical problems – Inadequate anticoagulation (international normalized ratio (INR) <2.0–3.0) – Atrial thrombus evident on transesophageal echocardiography (TEE) precluding DC CVN – Impaired transthoracic impedance Increased body mass index

Emphysema Insufficient contact between electrodes and chest wall – Inability to convert to NSR – Bradyarrhythmias • Contraindications: – Sinus tachycardia, multifocal atrial tachycardia, digoxin toxicity – Inadequate anticoagulation – Presence of atrial thrombus – Pulseless VT, ventricular fibrillation (VF)

Position

• Supine, arms tucked at sides • May be performed in the operating room (OR), emergency room (ER), on a stretcher or hospital bed

Incision

• None • Paddles or self-adhesive electrodes

Approximate Time

• Seconds for electrical discharge • Several minutes if multiple discharges are required • Anesthesia time 5–10 minutes

EBL Expected None

Hospital Stay

• Elective CVN is generally performed on an outpatient basis; observation for several hours after procedure • Semiurgent, emergent CVN is performed in the OR, or at the bedside

Special Equipment for Surgery

• ECG/defibrillator with synchronized discharge • Paddles (and conductive gel) or self-adhesive electrodes

EPIDEMIOLOGY Prevalence

Not available Morbidity

• Soreness or pain over chest wall, especially with repeated electrical discharges • Arrhythmias • Device malfunction if pacemaker or ICD present • Oral trauma

• Skin burns (insufficient conductive gel)

Mortality Rare

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Amnesia and analgesia are required for a short duration of time. • Patients with significant cardiac disease and functional impairment may deteriorate rapidly, even with reduced dosing and careful titration of sedation medications. • Precautions should be taken to avoid patient self-injury during electrical discharge. • Despite elective CVNs being performed frequently in remote locations (outside the OR), the same medications and equipment that are standard to the OR should be available • Emergent DC CVN may be life-saving in the perioperative setting in patients with unstable arrhythmias.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Palpitations, irregular heart beat • Shortness of breath, chest pain • Fatigue, reduced exercise tolerance • Lightheadedness, dizziness, syncope • Some patients asymptomatic

History

• Date of onset, frequency, duration of symptoms • Previous history atrial flutter, AF, VT • Cardiac and noncardiac diseases, cardiovascular risk factors (ischemia, myocardial infarct, valvular disease, coronary artery disease) • Alcohol, caffeine, drug, smoking history • Previous interventions (pacemaker, ICD, CVN, ablation procedures) • Medication changes or dosing changes

Signs/Physical Exam

Irregularly, irregular pulse MEDICATIONS

• New onset AF (<48 hours): Risk of thromboembolism is low; anticoagulation is not typically required before or after CVN • Paroxysmal AF (terminates spontaneously within 7 days, often within 24 hours) – Full anticoagulation – If INR <2.0–3.0, a TEE should be performed to rule out thrombus. – If no thrombus is evident, heparin must be started prior to CVN. – Anticoagulation should be continued for 4 weeks after CVN. – Anticoagulants include warfarin (most commonly prescribed), aspirin, heparin, low

molecular weight heparin, and clopidogrel. • Persistent AF (>7 days); same treatment as paroxysmal AF • Additional medications are usually prescribed in patients with long-standing AF to prevent stroke or other embolic events, atrial remodeling, or tachycardia-induced cardiomyopathy (3). • Rate control medications – Beta-blockers – Calcium channel blockers • Rhythm control medications – Flecainide, propafenone – Sotalol, dofetilide, ibutilide – Amiodarone, dronedarone – Verapamil – Quinidine

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• ECG – Atrial fibrillation: Irregularly, irregular R-R intervals, absence of P waves – Atrial flutter: Saw tooth pattern – SVT – Atrial tachycardia – Monomorphic VT • Coagulation profile • Chest radiograph to detect underlying cardiopulmonary pathology • Transthoracic echocardiography to identify underlying heart disease, dilated atria, atrial thrombus • 24-hour electrocardiographic monitoring or event recorder to diagnose paroxysmal AF • Electrolytes, CBC, INR • Renal, hepatic, and thyroid function • In urgent, emergent situations, acquisition of above should rarely preclude treatment.

CONCOMITANT ORGAN DYSFUNCTION

• Structural or valvular heart disease, hypertension, coronary artery disease • Obesity, obstructive sleep apnea, diabetes • Hyperthyroidism • Stroke, thromboembolic disease of the heart, lungs, kidneys, limbs

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines for anxious patients

• Heparin infusion when appropriate • Anti-arhyrhmic infusions when appropriate

Special Concerns for Informed Consent

• Emergency intubation or CPR if malignant ventricular arrhythmias or asystole occur and are unresponsive to medications • Possible oral trauma

INTRAOPERATIVE CARE Choice of Anesthesia

A continuum between deep sedation and general anesthesia Monitors

• Standard ASA monitors • Functioning IV (18, 20 gauge) with crystalloid infusion; in patients with severe cardiac disease, judicious fluid administration

Induction/Airway Management

• Supplemental oxygen via nasal cannula or face mask (simple, nonrebreather) in spontaneously breathing patients • If airway obstruction or apnea: – Jaw thrust – Positive pressure ventilation – In rare circumstances, urgent placement of endotracheal tube (ETT) or laryngeal mask airway (LMA) in patients who cannot be mask ventilated. • Induction agents titrated to loss of eyelid and glabellar reflexes – Propofol most commonly used – Etomidate may be substituted in patients with an ejection fraction (EF) <30–40% • Opiates may be added in patients with drug dependency • Elective intubation (LMA, ETT) in select patients (e.g., known difficult airway, aspiration risk).

Maintenance

• Procedure is typically of such a short duration that no additional medications are needed unless a repeat CVN must be performed. • Emergency medications should be available and ready for immediate administration (e.g., atropine, ephedrine, phenylephrine, epinephrine)

Extubation/Emergence

• Emergence and response to commands occurs as induction medications redistribute to peripheral compartments. • Generally 5–7 minutes, longer with repeated dosing for multiple shocks.

FOLLOW-UP

BED ACUITY

• Elective CVN – Outpatients – Observation to assure normal recovery from anesthesia – Treatment of postoperative problems such as nausea and vomiting • Semiurgent, emergent CVN – Observation to assure normal recovery from anesthesia, maintenance of NSR – Treatment of patients with unstable hemodynamics

ANALGESIA

• Not generally required • Fentanyl or ketorolac for pain, soreness

COMPLICATIONS

• Procedure related – Failed conversion to NSR – Bradyarrhythmias, reoccurrence AF – R-on-T phenomena, malignant ventricular arrhythmias, asystole (rare) – Accidental shock to healthcare personnel • Anesthesia related – Prolonged sedation – Hypoxia or inability to mask ventilate – Postoperative nausea and vomiting – Aspiration – Tongue, lip laceration if patients bite down during electrical discharge

PROGNOSIS

• Success rate is 90% when AF <1 year duration (5) and no underlying heart disease; 50% when arrhythmia present >5 yrs or atrial diameter >5 cm (2). • Adult monomorphic VT with pulse responds well to a single shock at 100 J (1).

REFERENCES

1. Link MS, Atkins DL, Passman RS, et al. Part 6: Electrical therapies: Automated external defibrillators, defibrillation, cardioversion, and pacing. 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(suppl 3):S706–S719. 2. Sucu M, Davutoglu V, Ozer O. Electrical cardioversion. Ann Audi Med. 2009;29(3): 201– 206. 3. Lafuente-Lafuente C, Mahe I, Extramiana F. Management of atrial fibrillation. Br Med J. 2010;340:40–45. 4. Khoo CW, Lip GYH. Acute management of atrial fibrillation. Chest. 2009;135:849–859. 5. Cakulev I, Efimov IR, Waldo AL. Cardioversion. Past, present, and future. Circulation. 2009;120: 1623–1632.

ADDITIONAL READING

• Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 guidelines for the management of patients with atrial fibrillation): Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114(7):E257–354.

CLINICAL PEARLS

• Elective CVN of atrial fibrillation (<1 year) has a 90% success rate with a single electrical discharge of 100–200 J. This value decreases to 50% when AF is present for longer than 5 years. • Induction agents should be titrated slowly, especially in patients with a low EF. • Protect the patient from self-injury as well as yourself from accidental shock. • In the perioperative setting, early DC CVN may be life-saving in patients with unstable arrhythmias. • Malignant ventricular arrhythmias and asystole are rare after CVN, but be prepared to treat. • Synchronized electrical cardioversion is NOT effective in focal and multifocal atrial tachycardias.

SYNCHRONIZED INTERMITTENT MANDATORY VENTILATION (SIMV) Lan Chi Tran, MD Daniel R.C. Nieva, MD

BASICS DESCRIPTION

• Synchronized intermittent mandatory ventilation (SIMV) is a time-cycled mode that provides a minimum level of ventilation, while allowing the patient to breathe spontaneously between preset mechanical breaths. It allows for three different types of breaths and prevents “breath stacking”: – Controlled or mandatory breath; a backup rate is set to prevent apnea or hyperventilation – Assisted (synchronized) breaths for spontaneously initiated breaths that fall within the synchronization window. Limits barotrauma from high peak pressures that could arise if a preset breath is delivered when the patient is maximally inhaled (breath-stacking) or forcefully exhaling (dyssynchrony). – Spontaneous breaths that occur outside the synchronization window (can be pressure supported). • SIMV was originally developed as a weaning mode; however, it is now popularly used as a primary mode of ventilation in the intensive care unit (ICU). In the operating room, under general anesthesia, it has also garnered popularity. Benefits can include – Improved patient comfort – Decreased “breathing against the ventilator” from asynchrony or “bucking;" this can theoretically decrease the need for sedation and muscle relaxants (1,2)[B]. – Decreased hyperventilation; prevents respiratory and left-shift of the oxygen-dissociation curve (decreased O2 unloading to tissue). • Parameters that need to be set: – FiO2

– Positive end-expiratory pressure (PEEP) – Method of support; preset tidal volumes (SIMV-Vol), pressure control level (SIMV-PC), or pressure support (SIMV-PSV) – Sensor sensitivity – Backup respiratory rate (RR) – Trigger window – I:E ratio

PHYSIOLOGY PRINCIPLES

• Full and partial ventilator support. Full ventilator support is provided when patients are apneic, sedated, or paralyzed. Partial ventilator support is provided when the patients are spontaneously ventilating.

• Interactive components of SIMV. Timing windows are used to give a mechanical breath during a pause in the patient’s respiratory cycle; should a spontaneous breath take place, the preset breath is synchronized to it. A spontaneous breath is detected by a flow sensor at the opening of the airway (at endotracheal tube [ETT] adaptor). The flow sensor is triggered by changes in airway pressure, airflow, and respiratory movements. Flow cycling (responsible for switching from expiration to inspiration) stops ventilator-derived breaths when spontaneous inspiration terminates and improves synchronization because the patient modulates the length of inspiration. These components function to prevent breath stacking. • Patient-triggered versus ventilator-triggered breaths. Spontaneous breaths that fall within the timing window are supported or synchronized. Spontaneous breaths that occur outside the synchronization window are not supported unless pressure support ventilation (SIMVPSV) is added. • Work of breathing (WOB). Spontaneous breaths incur energy and work. If they are not supported, it can result in increased WOB, tachypnea, abnormal breathing patterns, and respiratory fatigue (3,4)[A]. The addition of SIMV-PS serves to support the spontaneous breath, decreases work, and reduces shallow breaths that can result in atelectasis and shunting. Thus, WOB is inversely proportional to inspiratory pressure support. However, it does not abolish the breathing effort made by the patient; the WOB is equivocal to other controlled modes (2)[B]. • Settings – FiO2: As with most modes of ventilation, this needs to be selected. Patients are often started at an FiO2 of 1.0 with downward titration to avoid oxygen toxicity and decreased

surfactant production. – PEEP: Reduces atelectasis during expiration and results in improved oxygenation, lung volume (by increasing functional residual capacity), and lung compliance. Optimal PEEP is calculated based on the level at which static compliance is highest (generally 5–12 cm H2O). Avoid PEEPs >12–15 cm H2O that can result in overdistention of alveoli and

decreased cardiac output. – Method of support (tidal volume versus pressure control). In tidal volume support (SIMVVC), a volume is set for each ventilator delivered or synchronized breath. Peak inspiratory pressure (PIP) varies as lung compliance changes; and sudden drops in compliance can lead to barotrauma. In pressure control (SIMV-PC), a pressure is set for each ventilator delivered or synchronized breath; it prevents high PIP and thus prevents barotrauma. However, the tidal volume may change if lung compliance is dynamic. There can be a wide range of breath-to-breath tidal volumes and risk of hypocarbia. Inspiratory pressure support (SIMV-PS) is usually set at 30–50% of the difference between the PIP and PEEP; it aids with overcoming resistance imposed by an ETT and ventilator circuit for spontaneous patient breaths. – Sensor sensitivity is the amount of negative inspiratory force needed to trigger a breath from the ventilator. It is usually set at −1 to −2 cm H2O.

– Backup RR is typically at 8–12 breaths/minute. A higher rate decreases expiratory time and risks air trapping and auto-PEEP. – Trigger window is the proportion of expiratory pause that the ventilator waits for an

inspiratory effort. A spontaneous breath during this window will be “synchronized” and supported. – I:E ratio is typically set at 1:2. For obstructive airway disease, breath stacking, or autoPEEP, it is often changed to 1:2.5 to 1:4. Consider an inverse I:E ratio in poorly compliant lungs or ARDS.

ANATOMY

During SIMV, depth and rate of spontaneous ventilation is driven by the patient’s intrinsic ventilatory drive, and respiratory muscle effort. PHYSIOLOGY/PATHOPHYSIOLOGY

Adverse effects are similar to other modes of mechanical ventilation: • Ventilator-associated pneumonia (VAP) • Oxygen toxicity: Prolonged exposure to FiO2 >0.5 can result in alveolar membrane injury

from prolonged exposure to hyperoxia. The pathogenesis is believed to be secondary to excess oxidant production, lipid peroxidation, protein oxidant damage, and cell death. • Absorption atelectasis can occur at higher inspired oxygen fractions. In poorly ventilated alveoli, uptake/absorption of oxygen by blood exceeds replenishment and alveoli “collapse” (shunting). • Bronchopulmonary dysplasia. Chronic lung injury can be seen in neonates exposed to positive pressure ventilation and hyperoxia. Toxic factors cause injury to small airways and microvasculature, thus interfering with alveolar septation. SIMV has been shown to be associated with a lower risk of chronic lung injury in neonates (3)[B]. • Barotrauma/volutrauma. Inappropriate ventilator settings, plateau pressures >30 cm H2O, peak pressure >40 cm H2O. Lower risk with SIMV compared to other controlled modes of

ventilation. • Acute lung injury (ALI). High distending pressures in alveoli can increase vascular filtration pressure and microvascular permeability to protein as well as produce pulmonary capillary stress fractures and surfactant inactivation. Mucous flow can be impeded and lung rupture may occur. Mechanical damage leads to leakage of fluid, protein, and blood into the tissue and air spaces. • V/Q mismatch. Alveolar distension can compress vessels and result in decreased alveolar perfusion. • Decreased cardiac output. Increased intrathoracic pressure from positive pressure ventilation can decrease filling in the compliant right heart. This can result in decreased cardiac preload, which is exacerbated in the setting of hypovolemia. • Increased WOB and risk of respiratory fatigue if used without pressure support (5)[A].

PERIOPERATIVE RELEVANCE

• Intraoperatively, SIMV can be used to ensure a minimal level of ventilation in spontaneously breathing patients whose RR and effort will decrease after administration of narcotics, sedatives, and volatile agents. It is a useful tool during emergence and allows a smooth transition from full ventilator support to partial ventilator support to unsupported spontaneous breathing. Weaning can be achieved by

– Reducing the backup RR and/or the tidal volumes (decrease volume or pressure settings). Requires patient to take on greater proportion of breathing. – Decreasing ventilation to raise the paCO2 (permissive hypercarbia) above apneic threshold

and stimulate spontaneous breathing. – Conversely, increasing ventilation or SIMV rate (overbreathing) lowers the paCO2 below the resting paCO2 (apneic threshold) and depresses ventilatory drive.

• In the ICU, SIMV is commonly used to wean patients off mechanical ventilation. Studies in adults have not shown statistical differences in weaning duration, use of sedation, weaning fatigue, length of ICU stay, or mortality compared to other controlled modes (IMV & A/C) (1,2,5)[A]. Weaning can be achieved by – Decreasing the initial set rate to ∼2–4 breaths/minute every 12 hours as tolerated (monitor the rapid shallow breathing index and arterial blood gases) until a rate of 2–4 breaths/minute. – Adding PS (∼5–8 cm H2O) to overcome the resistance imposed by the ETT, ventilator tubing, and circuit valve. – Extubation can be considered if the patient is tolerating a backup RR <4/minute for >120 minutes. • Overall lower peak pressures with SIMV compared to other controlled modes in neonates has been shown to decrease chronic lung injury (3)[B].

EQUATIONS

• Tidal volumes depend on pulmonary status: – Normal Adult: 8–10 mL/kg of ideal body weight. – ARDS/ALI: 5– 8 mL/kg of ideal body weight, plateau pressure <30 cm H2O • Ideal body weight: – Male: 50 + 0.91 (height in cm – 152.4) – Female: 45.5 + 0.91 (height in cm – 152.4) • Minute ventilation at rest: TV × RR. (Normal adult: 5–8 L/min) • Lung compliance = ΔVolume (L)/ΔPressure (cm H2O)

GRAPHS/FIGURES

FIGURE 1. Pressure versus time for the three different types of breaths seen with synchronized intermittent mandatory ventilation (SIMV).

REFERENCE

1. Giuliani R, et al. Patient-ventilator interaction during synchronized intermittent mandatory ventilation. Effects of flow triggering. Am J Respir Crit Care Med. 1995;151:1–9. 2. Vitacca M, et al. Assessment of physiologic variables and subjective comfort under different levels of pressure support ventilation. Chest. 2004;126:851–859.

3. Reyes ZC, et al. Randomized, controlled trial comparing synchronized intermittent mandatory ventilation and synchronized intermittent mandatory ventilation plus pressure support in preterm infants. Pediatrics. 2006;118:1409–1417.

4. Patel DS, et al. Work of breathing during SIMV with and without pressure support. Arch Dis Child. 2009;94:434–436. 5. Ortiz G, et al. Outcomes of patients ventilated with synchronized intermittent mandatory ventilation with pressure support: a comparative propensity score study. Chest. 2010;137:1265–1277. See Also (Topic, Algorithm, Electronic Media Element) • Assist-controlled ventilation • Mechanical ventilation • Ventilator associated pneumonia • Positive end-expiratory pressure • Work of breathing

CLINICAL PEARLS

• SIMV delivers backup ventilation (rate and tidal volumes) in a manner that does not compete with the patient’s spontaneous efforts. • Suitable to general anesthesia where the ventilator can provide minimal minute ventilation or augment spontaneous effort in patients whose RR and efforts decrease with administration of anesthetic agents/narcotics.

SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION (SIADH) Adam Romanovsky, MD Sean M. Bagshaw, MD, MSc, FRCPC

BASICS DESCRIPTION

• The syndrome of inappropriate antidiuretic hormone (SIADH) causes an inability to excrete free water. It manifests as hypoosmolality and hyponatremia; total body sodium does not change. • SIADH presents as hyponatremia with normal total body sodium (Na+)

EPIDEMIOLOGY Incidence

Most common cause of hyponatremia in hospitalized patients. Prevalence

Exact prevalence is uncertain Morbidity

• Hyponatremia is associated with an increased duration of hospital stay and a higher rate of discharge to a long-term care facility. • May have added morbidity due to underlying illness (e.g., malignancy).

Mortality

Hyponatremia is associated with increased all-cause mortality in hospitalized patients. ETIOLOGY/RISK FACTORS

• Medications/drugs – Narcotic analgesics – Antipsychotics – Selective serotonin reuptake inhibitors – Tricyclic antidepressants – NDMA agonists (e.g., ecstasy) – Cyclophosphamide – Carbamazepine – ADH analogues (vasopressin, desmopressin, oxytocin) • CNS disorders – Meningitis, encephalitis, brain abscess – Stroke – Intracranial hemorrhage

– Post-transsphenoidal pituitary surgery – Intracranial tumor • Malignancy – Lung – Genitourinary tract – GI tract – Lymphoma • Pulmonary disease – Pneumonia – Tuberculosis – Parenchymal abscess – Empyema • Other – Pain – Nausea – Stress – HIV infection – Hereditary – Idiopathic

PATHOPHYSIOLOGY

• ADH is synthesized in the hypothalamus and is secreted from the posterior pituitary gland. It is normally released in response to an increase in serum osmolality, which is sensed by hypothalamic osmoreceptors. Release is also stimulated by activation of baroceptors in the aortic arch, carotid sinus, and left atrium as a result of low blood pressure and low cardiac output. • ADH binds to V2 receptors in the renal medullary collecting ducts leading to increased free water reabsorption (e.g., solute-free) via aquaporin-2 channels. This excess retention of solute-free water leads to hyponatremia by dilution of the patient’s serum sodium; the total body sodium does not change. • The SIADH describes the secretion of ADH independent of plasma osmolality or volume status. This results in – Increased free water reabsorption – Decreased serum sodium concentration – No change in total body sodium – Slightly increased body fluid volume – Increased urine osmolality – Decreased urine volume – No change in urine sodium excretion

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Identify and manage acute symptomatic hyponatremia before proceeding with the operation. • Prevent an excessive rise in sodium concentration in patients with documented chronic hyponatremia (>48 hours) as it can lead to osmotic demyelination (central pontine

myelinolysis). Correction should not exceed 0.5 mEq/L/hr • Avoid intraoperative exacerbation of hyponatremia by using IV fluids that are hypotonic to the patient’s urine. Worsening hyponatremia may lead to cerebral edema, seizures, and possibly death.

PREOPERATIVE ASSESSMENT SYMPTOMS

Hyponatremia: Ranges from asymptomatic to nausea, headache, lethargy, altered mental status, seizures, and coma. History

Underlying cause

Signs/Physical Exam

• Assessment of mental status • Assessment of volume status • Examination for features of underlying cause

TREATMENT HISTORY Free water restriction MEDICATIONS

• Loop diuretics (e.g., furosemide) • Demeclocycline • ADH antagonist therapy (tolvaptan or conivaptan

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Serum [Na+] <135 mEq/L • Serum osmolality <280 mOsm/kg • Urine [Na+] is dependent on the patient’s sodium intake as sodium excretion is not impaired (typically >40 mEq/L). • Urine osmolality is inappropriately high in the context of low serum osmolality. Exact osmolality depends on the degree of excess ADH activity; typically >300 mOsm/kg and may be significantly higher. • Serum creatinine and urea (typically normal) • Serum cortisol • Serum thyroid stimulating hormone

CONCOMITANT ORGAN DYSFUNCTION

Underlying causes can be pulmonary, CNS, or malignancy CIRCUMSTANCES TO DELAY/CONDITIONS

• Delay elective surgeries if the [Na+] <130 mEql/L to complete full workup and treatment. • Symptomatic hyponatremia (e.g., cardiac arrhythmias and mental status changes) • Proceeding with urgent or emergent surgery in these patients must be done with caution

CLASSIFICATIONS

• Hyponatremia is divided into acute (present for <48 hours) or chronic (present for >48 hours or if uncertain of the time of onset).

TREATMENT PREOPERATIVE PREPARATION Premedications

Benzodiazepines and opioids should be avoided in patients with an altered level of consciousness. INTRAOPERATIVE CARE Choice of Anesthesia

When possible, regional anesthesia may be preferred to facilitate monitoring of clinical manifestations in patients with neurologic abnormalities. Monitors

• Standard ASA monitors • Arterial line or central venous access can be useful for frequent blood sampling. Long operations may require frequent checks of serum sodium to ensure stability and guide fluid management. Induction/Airway Management

Symptomatic patients, especially those with cerebral edema, are at risk of increased intracranial pressure during intubation. Maintenance

• No specific technique has been shown to be superior to the other. Volatile anesthetics may lead to increased intracranial pressure from “uncoupling” of cerebral blood flow and oxygen consumption. • For hemodynamic support, avoid vasopressin or use with caution as it can worsen hyponatremia; acts as exogenous ADH. • Fluid choice should be guided by frequent surveillance of serum sodium and urine osmolality. Any fluid with lower osmolality than urine may lead to exacerbation of hyponatremia. – Normal saline (0.9% NaCl) and lactated Ringer’s solution have an electrolyte-based osmolality of 308 and 272 mOsm/kg, respectively. For many patients with SIADH, these fluids will be hypotonic in comparison to their urine. Therefore, use of these fluids (which are generally considered isotonic) may lead to worsening hyponatremia. This underscores the importance of frequent monitoring of serum Na+ in these patients.

– Hypertonic saline may be necessary in symptomatic or severe hyponatremia. This should be done with caution so as to avoid a rapid rise in serum sodium.

Extubation/Emergence

Increased confusion and decreased level of consciousness may preclude safe extubation.

POSTOPERATIVE CARE BED ACUITY

• Most patients can be managed safely in a regular floor bed unless precluded by an abnormal level of consciousness. • For symptomatic patients or those with rapid shifts in serum sodium, close observation should begin in the postoperative recovery unit and continued in an intensive care unit.

MEDICATIONS/LAB STUDIES/CONSULTS

• Repeat serum electrolytes (SIADH can be exacerbated by postoperative pain and nausea) • Consider nephrology consultation

COMPLICATIONS

• Worsening hyponatremia may lead to cerebral edema, seizures, and possibly death. • Rapid increase in serum sodium in chronic hyponatremia can lead to osmotic demyelination.

REFERENCES

1. Ellison DH, Berl T. The syndrome of inappropriate diuresis. New Engl J Med. 2007;356:2064–2072. 2. Hannon MJ, Thompson CJ. The syndrome of inappropriate antidiuretic hormone: Prevalence, causes and consequences. Eur J Endocrinol. 2010;162:S5–S12. 3. Sterns R, Cappuccio J, Silver S, et al. Neurologic sequelae after treatment of severe hyponatremia: A multicenter perspective. J Am Soc Nephrol. 1994;4:1522–1530. 4. Wald R, Jaber BL, Price LL, et al. Impact of hospital-associated hyponatremia on selected outcomes. Arch Int Med. 2010;170(3):294–302. See Also (Topic, Algorithm, Electronic Media Element) • Hyponatremia • Intracranial hypertension • Crystalloids • TURP syndrome

CODES ICD9 253.6 Other disorders of neurohypophysis

ICD10

E22.2 Syndrome of inappropriate secretion of antidiuretic hormone

CLINICAL PEARLS

• Do not ignore hyponatremia; SIADH requires a comprehensive workup. • IV fluid choice is patient and situation specific. The administration of fluid that is hypotonic to the patient’s urine can worsen hyponatremia; therefore, hypertonic saline may be necessary.

SYSTEMIC LUPUS ERYTHEMATOSUS Chitra Ramasubbu, MD

BASICS DESCRIPTION

• Systemic lupus erythematosus (SLE) has a complex pathogenesis with a link to autoimmunity against various native cellular components. • A diagnosis of SLE is made when patients meet 4 of the 11 criteria simultaneously or in succession. Criteria include: – Rash: Malar or discoid – Photosensitivity – Oral ulcers – Serositis (pericarditis, pleuritis) – Arthritis – Renal disorders (proteinuria, renal casts) – Neurological disorders (seizures, psychosis) – Hematological disorders (anemia, leukopenia, thrombocytopenia) – Positive anti-DNA antibody, anti-Sm antibody, antiphospholipid antibody – Positive antinuclear antibody • The multiple organ and system involvement has variable clinical presentations; optimal perioperative care by the anaesthetist requires a thorough understanding and awareness. EPIDEMIOLOGY Incidence

Ranges from 2 to 7.6 cases per 100,000 persons per year Prevalence

• National Health Survey reports a prevalence of 53.6/100,000. • Ten times more common in women than men with a predilection for women of childbearing age • Nine times more common in Afro-Caribbean females

Morbidity

• In a multicenter study of 1,000 patients followed over a 10-year period: Arthritis 48%; malar rash 31%; active neuropathy 28%; neurologic involvement 19%; Raynaud’s phenomenon 16%; serositis 16%; thrombocytopenia 13%; and thrombosis 9% • Myocardial ischemia is 50 times more likely to develop in women aged 44–55 years compared to healthy women as shown in the Framingham Offspring study. Mortality

• 10-year survival from the time of onset: 92%.

• 20-year survival from the time of onset: 68%.

ETIOLOGY/RISK FACTORS

• The exact etiology remains unknown. There appears to be a link to race, multiple susceptibility gene loci, hormones, and environmental factors. • Women of child-bearing age • African American women • Use of exogenous hormones • History of hypertension • Type I/II sun-reactive skin type • Family history of SLE • Smoking

PATHOPHYSIOLOGY

• It is hypothesized that abnormal apoptosis and intolerant lymphocytes are responsible for the disease’s manifestations. – Increased apoptosis may result from DNA methylation and is accompanied by plasma and nuclear antigen display on cell surfaces. – Normally, lymphocytes do not target these intrinsic antigens; however, abnormal lymphocyte signaling results in targeting of these cell surface antigens. – Antibody-antigen immune complexes form that can lodge in the microvasculature and cause complement activation. These complexes also become deposited on renal and skin basement membranes.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess for the severity of disease, including acute flares and end-organ damage. Careful attention should be paid to the cardiovascular, pulmonary, and renal systems. • Assess and evaluate for the need of “stress dose” steroids in patients with chronic steroid use.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Shortness of breath • Chest tightness • Cough • Tachypnea • Neuropathic pain

History

• Review disease course and presence of end-organ damage. – ER visits and hospitalizations – Treatment history – Triggers • A discussion with the patient’s rheumatologist (or note) can provide accurate information on

the history of the disease, course of the illness and current therapies.

Signs/Physical Exam

• Cardiovascular system exam – Murmurs may indicate valvular disease – Diminished heart sounds, friction rub may indicate pericarditis • Pulmonary exam – Diminished or inaudible breath sounds or coarse breath sounds may indicate pleural effusions, interstitial lung disease or pneumonia • Check for atlanto-axial subluxation signs

TREATMENT HISTORY

• Hemodialysis or renal transplant for chronic renal disease. • Pericardiocentesis or pericardial window for history of tamponade. • Mechanical valve replacement for Libman-Sacks vegetations; prosthetic valves are susceptible to valvulitis relapse.

MEDICATIONS

• Cyclophosphamide: Cardiotoxicity • Azathioprine and methotrexate: Hepatotoxicity • Methotrexate: Pulmonary fibrosis; when combined with NSAIDS can result in acute renal failure and pancytopenia • Mycophenolate: Pancytopenia • Long term steroids: Hyperglycemia, hypercholesteremia, osteoporosis, and hypertension • NSAIDS, aspirin: Peptic ulcers, platelet inhibition • Hydroxychloroquine: Retinotoxicity, cardiotoxicity, neurotoxicity

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC to rule out anemia, thrombocytopenia, leukopenia. If anemic, consider hemolysis workup. • Electrolytes, particularly in patients with lupus nephritis. • Liver function tests to investigate autoimmune hepatitis or drug hepatotoxicity. • Coagulation factors. An elevated PTT may be seen in patients with lupus anticoagulant. • Antibody and complement levels, if present, should be compared to previous values. • Antiphospholipid antibody indicates an increased risk of thrombosis. • Chest radiography can reveal interstitial lung disease, pneumonia, or pleural effusions. • EKG can reveal increased risk of myocardial ischemia, acute right heart failure, or PVCs. • Echocardiogram may be indicated if signs of endocarditis or valvular disease exist.

CONCOMITANT ORGAN DYSFUNCTION

• Neurologic – Increased risk of cerebrovascular disease, even in the absence of classic risk factors – Migraine or tension headaches are common • Cardiac

– Pericarditis, pericardial effusion, tamponade. – QT prolongation may result from hydroxychloroquine therapy. – Common arrhythmias include sinus tachycardia, atrial fibrillation, and atrioventricular block – Libman-Sacks vegetations are verrucous non-infective vegetations that can be seen on echocardiogram in ~1 in 10 SLE patients. • Pulmonary – Common parenchymal manifestations include interstitial lung disease, diffuse alveolar hemorrhage, and acute lupus pneumonitis. – In patients with pericarditis, there is an association with pleural effusions.

CIRCUMSTANCES TO DELAY/CONDITIONS • Acute flare • Serositis (pericarditis/pleuritis) • Upper respiratory infection • Pneumonia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Stress dose steroids may be indicated if the patient has been treated for more than 2 weeks within the past 6–12 months to avoid manifestations of adrenal insufficiency. Steroids with glucocorticoid and mineralocorticoid activity should be administered. • Anxiolysis as needed • Patients with a history of thrombosis may warrant therapeutic anticoagulation. Discuss with the hematologist and surgeon prior to starting. • Aspiration prophylaxis should be considered • Appropriate antibiotic therapy is warranted secondary to the increased risk for infection

Special Concerns for Informed Consent

Discuss the need for invasive monitoring, if applicable INTRAOPERATIVE CARE Choice of Anesthesia

Neuraxial and regional anesthesia may be contraindicated in patients that have a baseline coagulopathy, are being anticoagulated, or need to be anticoagulated in the immediate postoperative period. Monitors

• Standard monitors • Consider arterial line in high-risk surgeries (patient population with increased cardiac risk)

Induction/Airway Management

• Laryngeal mask airways (LMAs) sit supraglotically and may minimize airway manipulation and edema. Post-intubation subglottic stenosis is a potential in patients with active SLE, even after brief periods of intubation. • Endotracheal tubes – A rapid sequence intubation (RSI) may be indicated in patients with gastroesophageal reflux (present in 11–50% of patients) – Laryngeal edema, subglottic stenosis, and vocal cord paralysis can make laryngoscopy and intubation difficult – Oral mucosal ulceration may be present in one-third of patients; laryngoscopy should be performed gently • Muscle relaxation – Increased doses of nondepolarizing muscle relaxants may be needed. One study demonstrated that there is a 20% dose increase for vecuronium, 45% for pancuronium, and 37% for atracurium – Succinylcholine may have a prolonged duration of action in patients taking cyclophosphamide (a pseudocholinesterase inhibitor). Succinylcholine is metabolized in the plasma by pseudocholines- terase enzyme.

Maintenance

• Proper positioning with padding can prevent peripheral nerve compression and fractures of osteoporotic bones • Eye protection and lubrication can prevent corneal abrasions. Sjögren’s syndrome predisposes to corneal abrasions. • Drug interactions with immunosuppressants – Nitrous oxide may worsen bone marrow suppression. – Muscle relaxants (see above) • Lupus nephritis – Maintain adequate urine output with proper fluid resuscitation (frequent monitoring and adjustments to fluids). – Avoid hypotension – Avoid nephrotoxic drugs • Avoid Raynaud’s phenomenon by – Maintaining normothermia – Humidifying and warming inspiratory gases

Extubation/Emergence

Cricoarytenoid arthritis may cause airway obstruction following tracheal extubation.

POSTOPERATIVE CARE BED ACUITY

• Vigilance for airway obstruction • Consider supplemental oxygen (nasal cannula, face mask); incentive spirometry to reduce atelectasis • Thromboprophylaxis includes early mobilization and pharmacologic anticoagulation

• Good pain control

COMPLICATIONS

Drug-induced SLE may result from treatment with procainamide, hydralazine, isoniazid, penicillamine, and alpha-methyl dopa.

REFERENCES

1. Ben-Menachem E. Review article: Systemic lupus erythematosus: A review for anesthesiologists. Anesth Analg. 2010;111(3):665–676. 2. http://www.niams.nih.gov 3. Manson JJ, Rahman A. Systemic lupus erythematosus. Orphanet J Rare Dis. 2006;27(1):6. 4. www.lupus.org

See Also (Topic, Algorithm, Electronic Media Element) • Pericardial tamponade • QT prolongation

CODES ICD9 710.0 Systemic lupus erythematosus ICD10 M32.9 Systemic lupus erythematosus, unspecified

CLINICAL PEARLS

• Perioperative management of SLE patients should be tailored to the individual patient. • Assess severity of disease and organ involvement in order to plan an appropriate anesthetic technique. • Patients with SLE may present for procedures specific to the disease (renal transplants, pericardial windows) or for nonrelated procedures (pregnancy).

SYSTOLE

Srikantha L. Rao, MBBS, MS Niraja Rajan, MB, BS, FAAP

BASICS DESCRIPTION

• In simple terms, systole is the time during which the ventricles contract and eject blood. It is followed by diastole (a period of relaxation), and a set of these events in both the atria and ventricles comprises a cardiac cycle. – The sino-atrial (SA) node, also known as the cardiac pacemaker, spontaneously and rhythmically initiates each cardiac cycle. The action potential at the SA node is propagated through both atria (atrial contraction – P wave on EKG) and then through the atrio-ventricular node (PR interval on EKG), His bundle and Purkinje system to both ventricles (QRS complex on EKG). Ventricular repolarization is seen as the T wave on the EKG. – Isovolumic contraction. During the first phase of left ventricular (LV) systole, the ventricle begins contraction with the mitral and aortic valve closed leading to a rapid increase in intraventricular pressure but no change in volume. – Ejection phase: The second phase of systole begins with the opening of the aortic valve (ventricular pressure exceeds the aortic pressure) and ends when the ventricle has stopped contracting, although ejection is still taking place (the aortic valve is still open). – Diastole: Marks the onset of ventricular relaxation. Ejection into the aorta continues until the left ventricular pressure drops below the aortic pressure and the aortic valve closes. • Physiologic systole begins at the start of isovolemic contraction and ends at the peak of ventricular ejection. Clinical systole (by echocardiography) begins with mitral valve closure and ends with aortic valve closure. • Systole and diastole require energy. During diastole, ventricular relaxation occurs by the removal/uptake of calcium from troponin C and into the sarcoplasmic reticulum. The factors that affect systolic function, preload, afterload, heart rate and contractility overlap the effects of calcium on the ventricle. PHYSIOLOGY PRINCIPLES

• The amount of blood ejected by the ventricle with each contraction is the stroke volume (SV). Normal SV in an adult man is 70–80 mL. SV is determined by preload, afterload, and contractility. The description below pertains to LV systolic function. The amount of blood ejected by the heart per minute is the cardiac output (CO). • Preload – Is the load on the ventricle before contraction and is determined by ventricular volume. – It is the end-diastolic myocardial fiber length and is represented by the end-diastolic volume (EDV); normally around 120 mL. – Cardiac muscle develops most of its force over a small range of shortening near its

maximal length. Thus, within limits, increases in preload (rise in EDV) will increase the SV and systolic pressure. – Factors affecting preload include venous return (including venous tone), total blood volume, intrathoracic pressure, body position, and atrial contraction. – Surrogate measures of LV volume used to estimate EDV are pulmonary capillary wedge pressure (PCWP) or central venous pressure (CVP). • Afterload – Is the load on the ventricle at the start of a contraction. In simple terms, afterload is the impedance to ejection of blood. – Most of the resistance to ejection is from the systemic vascular resistance (SVR). – An increase in afterload decreases ventricular ejection. – Ventricular wall stress (tension) is a concept that incorporates both preload and afterload. Arterial blood pressure, vascular compliance and volume, and wall thickness all factor into tension. It can be calculated by LaPlace’s law: Tension = (change in pressure) (ventricular radius)/(wall thickness ×2). • Contractility – Is the muscle’s ability to generate work (contract, develop pressure, generate a contractile force) from a set end-diastolic fiber length. – Increased contractility refers to a greater velocity of contraction (Vmax) reaching a higher

peak force. This definition is useful at the subcellular level to measure contractility in isolated papillary muscle. – Another measure of contractility, the rate of pressure development (dP/dt), is not used clinically. – Ejection fraction (EF) is a clinically useful index of contractility. • Both systolic and diastolic function can be assessed using pressure-volume curves that can be obtained during cardiac catheterization. • Coronary blood flow – 75% of total coronary blood flow occurs during diastole. During systolic contraction, there is an increase in tissue pressure that impedes arterial flow; blood is redistributed from the subendocardial to the subepicardial layer of the LV. Systole has minimal impact on coronary flow to the right ventricle (RV). – Coronary blood flow at rest is about 250 mL/min (4–5% of CO) or 75 mL/100 g/min, assuming the adult heart weighs 300 g and the CO is 5 L/min. – The myocardial oxygen consumption at rest is 8–10 mL/100 g/min, about 10% of the total body consumption of oxygen. – In the coronary circulation, near maximum oxygen extraction (75% of arterial oxygen content) occurs during rest. Hence, an increase in coronary blood flow is necessary when myocardial oxygen consumption occurs. – Heart rate, LV wall stress, and contractility determine myocardial oxygen consumption.

ANATOMY

• The heart consists of two atria and two ventricles that circulate blood in series; the RV pumps through the low-resistance pulmonary circulation, while the LV pumps through the high-resistance systemic circulation.

• The RVs and LVs differ in their shape, size, and pressure against which they contract. • The LV is ellipsoidal in shape with the muscle fibers arranged longitudinally in the subepicardium and subendocardial layers, and circumferentially in between these two layers. The LV ejects blood with a corkscrew type of motion with the apex moving toward the base. Wall motion of regions supplied by branches of the coronary artery can be individually assessed semi-quantitatively by echocardiography. • The RV is crescent-shaped with an inflow and outflow region that contract sequentially to eject blood into the low-pressure pulmonary circulation. 3-D echocardiography is becoming useful in quantifying RV systolic function. • The atrial systole contributes 25–30% of the volume toward ventricular filling, and the SV could significantly decrease in the absence of this atrial contraction during cardiac dysrhythmias and could also be compounded by impaired relaxation of the ventricles, for example, during atrial fibrillation in older patients. PERIOPERATIVE RELEVANCE

• Electrical activity of the heart is monitored using the ECG, while the mechanical events are monitored using the arterial and pulmonary BP or echocardiography. • A pulmonary artery catheter has been traditionally used to estimate CO by thermal dilution. Assuming a normal LV systolic and diastolic function, EDV is estimated from left ventricular end-diastolic pressure (LVEDP). In disease states where ventricular compliance is abnormal, LVEDP correlates poorly with CVP/PCWP. • With transesophageal echocardiography (TEE), EDV can be directly measured, as well as estimate the EF. • The majority of intravenous induction agents decrease BP via venodilation (decreased preload) and/or vasodilation (decreased afterload). • Isoflurane, desflurane, and sevoflurane used for maintenance of anesthesia (1–1.5 MAC), decrease SV by 15–30%. An increase in heart rate caused by these inhaled agents may minimize the decrease in CO. • Positive-pressure ventilation (PPV) leads to raised intrathoracic pressure leading to reduced venous return, in turn reducing SV and thereby BP. The onset of positive pressure ventilation is associated with a greater decrease in RV function compared to LV function; however, with time, the reduction in RV output will decrease LV output. During PPV, the SV varies with inspiration and exhalation. When this variation is >15%, it may be indicative of relative hypovolemia and volume responsiveness. • Newer pulse contour analysis monitors allow estimation of LV SV from systemic arterial pressure waveforms. • Stand-alone monitors exist that use esophageal Doppler probes to estimate SV. These probes measure the velocity (peak and mean) of blood in the descending thoracic aorta, and by integrating it over the ejection time, obtain the velocity time integral (VTI). VTI multiplied by the cross-sectional area of the aorta (assuming a diameter, given the patient’s age, gender, and height and weight) provides the SV with every beat. A similar method may be used to estimate SV using TEE. EQUATIONS

• In a normal-sized human with a heart rate (HR) of 70–80 beats per minute, cardiac output

(CO) is 5–6 L/min. – CO = SV × HR • Cardiac index (CI) is CO indexed to bodies of varying sizes, expressed using body surface area (BSA) – CI = CO/BSA • SVR = (MAP – CVP)/CO × 80 – MAP is mean arterial pressure – CVP is central venous/right atrial pressure – Normal SVR is 900–1,500 dynes.sec.cm−5 • LV wall stress = (Pressure × Radius)/(2 × Wall thickness) • EF = (EDV – ESV)/EDV – EF is ejection fraction – ESV is end-systolic volume – EDV is end-diastolic volume – SV is stroke volume

REFERENCES

1. Hunter WC, Janicki JS, Weber KT. Mechanical properties of the ventricle during systole. Fed Proc. 1980;38(2):169–174. 2. Meller J, Herman MV, Teichholz LE. Noninvasive assessment of left ventricular function. Adv Intern Med. 1979;24:331–357. 3. Shoucri RM. Studying the mechanics of left ventricular contraction. IEEE Eng Med Biol Mag. 1998;17(3):95–101. See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary artery catheter waveforms • Cardiac output • Cardiac output, methods to measure • Diastole • Afterload

CLINICAL PEARLS

• Systole and diastole are both energy-requiring processes. • Adequate and judicious IV hydration before induction of anesthesia is recommended, especially in the older patient, to minimize the cardiovascular effects of the induction drugs and PPV. • When compared to other methods, an increase in CO achieved by optimizing intravascular volume that increases venous return (preload) is the most efficient method, as it does not lead to increased oxygen consumption. • A dilated, thin-walled ventricle (failing ventricle) has greater wall stress than a thickerwalled, smaller ventricle. When hydrating patients with heart failure, reducing afterload is important. • Hypoxia, acidosis, ischemia, calcium-channel blockers and beta-blockers decrease

contractility.

TACHYCARDIA

Piotr K. Janicki, MD, PhD Marek Postula, MD, PhD

BASICS DESCRIPTION

• Tachycardia is defined as an arrhythmia with a rate >100 beats per minute. • Tachycardia can be classified in several ways based on the appearance of the QRS complex (wide- or narrow-QRS complex), origin (supraventricular or ventricular), and regularity (regular or irregular). – A narrow-QRS complex (QRS <0.12 seconds) supraventricular tachycardia (SVT) originates above or within the atrioventricular (AV) node. Examples include (in the order of observed incidence): sinus tachycardia, atrial fibrillation and flutter, AV nodal reentry, accessory pathway-mediated tachycardia, atrial tachycardia, multifocal atrial tachycardia (MFAT), and junctional tachycardia (rare in adults). – A wide-QRS complex tachycardia (≥0.12 seconds) usually originates outside of the normal conduction system and may be either ventricular or supraventricular in origin. Examples include ventricular tachycardia (VT), ventricular fibrillation (VF), preexcited tachycardia (Wolff–Parkinson–White (WFW) syndrome), ventricular-paced rhythms, and SVT with aberrancy (the latter represents tachycardia with supraventricular origin). • Perioperatively, tachycardia may be an early indicator of an underlying condition and warrants evaluation, treatment of the underlying cause, and possibly symptomatic treatment of the heart rate, particularly in unstable patients. EPIDEMIOLOGY Prevalence

• SVT is common across all age groups • Regular SVT (or paroxysmal SVT) is more likely to be encountered in the younger patient with no structural heart disease as compared to atrial fibrillation, which has a 70% concentration in those older than 65 years of age. Prevalence

In 1996, the estimated prevalence of all tachycardias in the US was 2.3 million. Morbidity

• Arise principally from spontaneous degeneration into the more malignant ventricular rhythms, including VF. • Can precipitate myocardial ischemia

Mortality

Reported mortality from SVTs is primarily associated with atrial fibrillation and flutter.

ETIOLOGY/RISK FACTORS

• Narrow complex tachycardia – Sinus tachycardia (enhanced catecholamine release) or reflexively Hypoxia Acute coronary ischemia and myocardial infarction Acidosis Hypotension and shock Volume depletion Anemia Hypoglycemia Pain, light anesthesia, awareness, anxiety Fever, hyperthermia Bladder distension Shivering Sepsis Pulmonary embolism Medications: Anticholinergics, beta-agonists (ephedrine, epinephrine), desflurane Rare causes: Pheochromocytoma, hyperthyroidism, malignant hyperthermia • Cardiac conduction disease: AV nodal reentry, accessory pathway-mediated, multifocal tachycardia • Wide complex tachycardia – Ischemia – Bundle branch block – Tricyclic antidepressant overdose – Hyperkalemia

PHYSIOLOGY/PATHOPHYSIOLOGY

• Sinus tachycardia is usually the result of sympathetic nervous system activation in concert with a decrease in cardiac vagal tone. No specific drug treatment is required. The therapy should be directed toward identification and treatment of the underlying cause. Concurrent symptomatic rate reduction may be considered in patients at risk for ischemia from increased myocardial oxygen consumption or decreased supply (e.g., coronary artery disease) • Narrow-QRS complex tachycardia is the most commonly seen arrhythmia during the perioperative period. The mechanisms of this tachycardia include – Reentry SVT: Caused by abnormal rhythm circuit that allows a wave of depolarization to repeatedly travel in a circle in cardiac tissue. – Abnormal automaticity. Due to rapid repetitive depolarization from a single cell or group of cells is the basic mechanism for MFAT, focal (ectopic) atrial tachycardia, and junctional tachycardia. These arrhythmias can be difficult to treat, are not responsive to cardioversion, and are usually controlled with drugs that slow conduction through the AV node with subsequent slowing of the ventricular rate.

PREVENTATIVE MEASURES

Aimed at avoidance of causes:

• Avoid hypoxia • Optimize myocardial oxygen supply and demand • Maintain fluid hydration • Transfuse red blood cells, if appropriate • Provide an adequate depth of anesthesia and analgesia • Identify patients at risk for DVT and initiate appropriate prophylaxis • Give anticholinergics slowly, when coadministered with anticholinesterases • Optimize underlying comorbid conditions • Continue perioperative antibiotics • Continue perioperative beta-blockade, as appropriate

PREOPERATIVE ASSESSMENT • Rule out life-threatening causes of tachycardia: Hypoxia, ischemia, and acidosis. • Review the EKG to assess wave morphology – Narrow-QRS complex (SVT) tachycardia has a QRS <0.12 seconds. Assess rate, regularity, and P-wave presence and morphology. – Wide-QRS complex tachycardia has a QRS interval ≥0.12 seconds • Sinus tachycardia – Review recent events (intubation, blood loss, incision or surgical stimulation, movement, other vital signs) and medications administered • Wide complex tachycardia: To distinguish between ventricular and SVT (with aberrations) origin: – Maneuvers (i.e., carotid sinus pressure and Valsalva maneuver) – the response of the arrhythmia to maneuvers may provide insight to the mechanism of the wide complex tachycardia (SVTs tend to stop with this maneuver while ventricular arrhythmias do not). – Diagnostic pharmacologic interventions: SVT: Verapamil, diltiazem, adenosine, or beta-blockers will terminate PSVT and slow SVT VT: Procainamide, sotalol, or amiodarone may terminate the rhythm. Adenosine will not stop or slow down. Laboratory tests • Arterial blood gas to assess for hypoxia, acidosis, and anemia • Plasma potassium and magnesium concentrations. Hypokalemia and hypomagnesemia both predispose to the development of ventricular tachyarrhythmias. Hyperkalemia can cause a wide-QRS complex rhythm with the loss of a detectable P-wave, although this usually has a slow rate (so-called “sinoventricular rhythm”). In patients taking digoxin, quinidine, or procainamide, consider measuring plasma concentrations to assist in evaluating possible toxicity. • Chest x-ray (cardiomegaly or evidence of previous cardiac surgery) DIFFERENTIAL DIAGNOSIS

• Narrow complex tachycardia

– Sinus tachycardia – Atrial fibrillation or flutter – AV nodal reentry – Accessory pathway-mediated tachycardia • Atrial tachycardia – Multifocal atrial tachycardia – Junctional tachycardia (rare in adults) • Wide complex tachycardia – Ventricular tachycardia – Ventricular fibrillation – Supraventricular tachycardia with aberrancy – Preexcited tachycardia (WPW syndrome) – Ventricular-paced rhythms

TREATMENT • If the patient is hemodynamically unstable (hypotension, acutely altered mental status, signs of shock, chest pain, acute heart failure), proceed immediately to appropriate electrical shock therapy (synchronized cardioversion or defibrillation for VF): – Synchronized cardioversion initial recommended dose: Narrow regular: 50–100 J Narrow irregular (e.g., atrial fibrillation): 120–200 J biphasic or 200 J monophasic Wide regular: 100 J Wide irregular (defibrillation dose – NOT synchronized): 360 J monophasic or 120–200 J biphasic Pediatric: Initial dose of 2–4 J/kg. Subsequent energy levels may be considered, but should not exceed 10 J/kg. – Not effective for multifocal and focal atrial tachycardia • Polymorphic VT requires immediate defibrillation with the same strategy used for VF. Prevention of recurrent polymorphic VT may be performed with magnesium, pacing, and/or sotalol, amiodarone, or procainamide. • Stable ST. Treatment should be aimed at the underlying cause. In patients at risk for myocardial ischemia or demonstrating hemodynamic compromise, consider rate control with beta-blockers. • Regular, stable narrow complex tachycardia – Vagal maneuvers – Consider: Beta-blockers or calcium channel blockers – Amiodarone may be considered in patients with congestive heart failure – Adenosine 6 mg IV followed by a 20 mL saline flush; may repeat with a 12 mg rapid IV push after 1–2 minutes. • Stable wide-QRS tachycardia: – Procainamide, amiodarone, sotalol

FOLLOW-UP

• Patients who develop sustained and/or nonsustained VT during the perioperative period should be referred to a cardiologist for further evaluation, including an evaluation of their ventricular function and screening for heart ischemia. • Several studies suggest beta-blocker therapy can reduce mortality and the incidence of cardiovascular complications (including the development of arrhythmias) during surgery, and for up to 2 years afterward. • For long-term treatment of SVTs: AV nodal blocking agents (e.g., verapamil, diltiazem, betablockers, digoxin), amiodarone, and disopyramide may be started by cardiology. • Radiofrequency ablation is a safe, effective, and cost-effective method for suppressing SVT.

REFERENCES

1. Neumar Link MS, Atkins DL, Passman RS, et al. Part 6: Electrical therapies: Automated external defibrillators, defibrillation, cardioversion, and pacing: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 Suppl 3):S706–S719. Neumar RW, Otto CW, Link MS, et al. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(suppl 3):S729–S767. Reising S, Kusumoto F, Goldschlager N. Lifethreatening arrhythmias in the intensive care unit. J Intensive Care Med. 2007;22(1):3–13. 2. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines: Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114(10):e385–484. See Also (Topic, Algorithm, Electronic Media Element) • Atrial fibrillation • Ventricular tachycardia • Ventricular fibrillation • Bradycardia • Intraoperative hypoxia • Anemia • Intraoperative myocardial ischemia • Atrial tachycardias

CODES ICD9 • 427.1 Paroxysmal ventricular tachycardia • 427.89 Other specified cardiac dysrhythmias • 785.0 Tachycardia, unspecified

ICD10

• R00.0 Tachycardia, unspecified • I47.1 Supraventricular tachycardia • I47.2 Ventricular tachycardia

CLINICAL PEARLS

• When the heart rate is <150/min, it is unlikely that symptoms of instability are caused primarily by the tachycardia unless there is impaired ventricular function or structure (e.g., outflow tract obstruction, aortic stenosis, mitral stenosis, etc). • When cardiac function is poor, cardiac output can be dependent on a rapid heart rate. In such compensatory sinus tachycardias, stroke volume is limited; thus, decreases in the heart rate can be detrimental (e.g., induction of general anesthesia with cardiac tamponade). • If the tachycardia is suspected to be the cause of acute altered mental status, ischemic chest discomfort, acute heart failure, hypotension, or other signs of shock, the patient should receive immediate synchronized cardioversion. • If there is any doubt whether monomorphic or polymorphic VT is present in the unstable patient, provide high-energy defibrillation without waiting for detailed analysis of the rhythm. • Active tachyarrhythmias for which the patient should undergo evaluation and treatment before noncardiac surgery: – Symptomatic ventricular arrhythmias – Supraventricular arrhythmias (including atrial fibrillation) with uncontrolled ventricular rate (heart rate >100 bpm at rest) – Newly recognized VT.

TARDIVE DYSKINESIA

Russell K. McAllister, MD Tricia A. Meyer, PharmD, MS, FASHP

BASICS DESCRIPTION

• Tardive dyskinesia (TD) is a severe, and potentially irreversible, adverse effect of long-term pharmacologic therapy with dopamine receptor antagonists, primarily in the form of antipsychotic drugs. – Characterized by purposeless, involuntary, and repetitive movements in single or multiple body regions. – Tardive comes from the French word “tardif,” which means tardy or late. The abnormal movements usually occur “late” in therapy with antipsychotic medications. – Dyskinesia comes from the Greek words “dys” and “kinesis” and means difficulty of movement. – Antipsychotic medications function mainly as antagonists at postsynaptic dopamine receptors (primarily dopamine-2 receptor). They are most commonly used in the treatment of psychiatric disorders such as schizophrenia. – More than 20% of patients in nursing homes are administered antipsychotics for behavioral issues associated with dementia; therefore, the perioperative impact of TD should be expected to increase as our surgical population increases in age. • TD has an incidence of 2–4% per year of treatment with neuroleptic antipsychotics. • Acute dystonic reactions (ADRs) differ from TD in that movement-related issues following administration of antipsychotic or antiemetic agents usually occur within 48 hours of treatment onset. – These reactions are rarely life threatening, but frequently anxiety inducing. – Dystonic reactions are characterized by abnormal contractions of muscle groups in abnormal positions and frequently lead to tremendous patient discomfort. ANATOMY

• The orofacial area is mainly affected by classic TD with quick, involuntary movements that may include – Blinking – Grimacing – Smacking – Licking – Sucking – Puckering – Chewing – Tongue movements • The trunk and limbs may display choreoathetoid movements. This is described as snake like

or twisting movements.

PHYSIOLOGY/PATHOPHYSIOLOGY

• It is considered to be a disorder of dopamine systems, and evidence suggests that chronic dopamine blockade results in receptor sensitivity and may be involved in the pathogenesis of TD. • The specific pathophysiology of TD is not fully understood but may involve the formation of free radicals and mitochondrial energy failure. • Factors that may increase the incidence of TD include – Advanced age (especially in women; thought to be due to decreased estrogen levels and increased phenylalanine levels) – Greater than 6 months duration of use of a first-generation antipsychotic – History of Parkinsonian side effects – Previous brain injury – Phenylketonuria (increased levels of phenylalanine levels). • Symptoms may first appear around, or after, 6 weeks of antipsychotic therapy but are more commonly seen with therapy of 2 years or longer. • The disorder is difficult to treat and prompt withdrawal of the offending drug is recommended. Typically, approximately one-third of patients with TD will have resolution within 3 months of discontinuation of the offending medication. Most will have a remittance within 5 years. Additionally, TD may actually worsen upon discontinuation or reduction in dose of the antipsychotic medication following years of therapy.

• Atypical, or second-generation, antipsychotic drugs may have a lower incidence of TD compared to typical antipsychotics. Clozapine and quetiapine have the lowest incidence. • Subtypes of TD include: – Tardive akathisia: Frequent, complex stereotyped movements. Legs are commonly involved (marching or walking in place, crossing/uncrossing). Additionally, trunk rocking, respiratory grunting/moaning, and complex hand movements (face rubbing or scratching) – Tardive dystonia: Involuntary movements that resemble multiple movement disorders (generally slower and more sustained) – Tardive tics, myoclonus, stereotypy, and tremor may also be included as subtypes • A diagnosis of TD is made after exclusion of other movement disorders and is usually diagnosed by physical exam as well as neuropsychiatric and medication history. Other druginduced movement disorders include – Acute dystonia – Neuroleptic malignant syndrome – Neuroleptic-induced Parkinsonism – Asterixis, chorea – Serotonin syndrome

PERIOPERATIVE RELEVANCE

• Acute, short-term, perioperative use of antidopaminergic agents will not cause a patient to develop TD. Additionally, there is no known evidence that administration leads to a quicker

onset of TD symptoms in patients on long-term antidopaminergic therapy. However, in patients with, or having a history of, TD, it is possible that antidopaminergics can worsen or cause a remission. – Anticholinergics and serotonin-specific reuptake inhibitors have antidopaminergic effects. – Antiemetic drugs Metoclopramide and prochlorperazine are dopamine-blocking agents. TD may occur after prolonged use. In 2009, the FDA issued a Black Box Warning for long term and high dose use of metoclopramide related to the high risk of developing TD. Haloperidol, perphenazine, and droperidol are antiemetic agents also classified as antipsychotics. These drugs are used in the perioperative period. 5-hydroxytryptamine-3 receptors (“tron” drugs such as ondansetron and dolasetron) may be safer choices for the treatment of postoperative nausea and vomiting in patients who are known to have TD. This class of drugs is not associated with TD or ADRs. – Calcium channel blockers have also been rarely implicated. • Respiratory distress may manifest from laryngeal or diaphragmatic dyskinesia. • ADR that are not classified as TD may present perioperatively with the acute use of antiemetic medications that have antidopaminergic effects. – The antihistamine diphenhydramine, due to its anticholinergic properties, has been used to treat this disorder with good success. – In addition, benztropine and benzodiazepines have also been used successfully. Effective doses may vary. – Routine use of metoclopramide in women prior to Cesarean section may increase the incidence of ADR. Risks and benefits of metoclopramide should be considered in this patient population at higher risk for aspiration of gastric contents.

GRAPHS/FIGURES

• Typical (first-generation) antipsychotics – Chlorpromazine (Thorazine®) – Droperidol (Inapsine*). Approved indications for droperidol are to reduce incidence of nausea and vomiting, although it may also be classified as an antipsychotic agent. – Fluphenazine (Prolixin®) – Haloperidol (Haldol®) – Loxapine (Loxitane®) – Perphenazine (Trilafon®) – Pimozide (Orap®) – Thiothixene (Navane®) – Thioridazine (Mellaril®) – Trifluoperazine (Stelazine®) • Atypical (second-generation) antipsychotics – Aripiprazole (Abilify®) – Asenapine (Saphris®) – Clozapine (Clozaril®) – Iloperidone (Fanapt®)

– Lurasidone (Latuda®) – Olanzapine (Zyprexa®, Zyprexa, Zydis®) – Paliperidone (Invega®) – Quetiapine (Seroquel®) – Risperidone (Risperdal®, Risperdal Consta®) – Ziprasidone (Geodon®)

REFERENCES

1. Barak Y, Swartz M, et al. Vitamin E (alpha-tocopherol) in the treatment of tardive dyskinesia: A statistical meta-analysis. Ann Clin Psychiatry. 1998;10(3):101–105.

2. Burke RE, Kang UJ, Jankovic J, et al. Tardive akathisia: An analysis of clinical features and response to open therapeutic trials. Mov Disord. 1989;4(2):157–175. 3. Chou K, Friedman J. Tardive syndromes in the elderly. Clin Geriatr Med. 2006;22:915–933. 4. Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 17th edn. 2008; New York, NY: McGraw-Hill. 5. Koek RJ, Pi EH. Acute laryngeal dystonic reactions to neuroleptics. Psychosomatics. 1989;30:359–364. 6. Lencz T, Malhorta A. Pharmacogenetics of antipsychotic-induced side effects. Dialogues Clin Neurosci. 2009;11(11):405–415. 7. Mejia NI, Jankovic J. Tardive dyskinesia and withdrawal emergent syndrome in children. Expert Rev Neurother. 2010;10(6):893–901. 8. Rao A, Camilleri M. Review article: Metoclopramide and tardive dyskinesia. Aliment Pharmacol Ther. 2010;31:11–19. 9. Soares-Weiser K, Fernandez H. Tardive dyskinesia. Semin Neurol. 2007;27:159–169. 10. Wemove.org is a website devoted to education regarding movement disorders. 11. Woods SW, Morgenstern H, Saska JR, et al. Incidence of tardive dyskinesia with atypical versus conventional antipsychotic medications: A prospective cohort study. J Clin Psychiatry. 2010;71(4):463–474. See Also (Topic, Algorithm, Electronic Media Element) • Schizophrenia

CODES ICD9 333.85 Subacute dyskinesia due to drugs ICD10 G24.01 Drug induced subacute dyskinesia

CLINICAL PEARLS

• Abrupt withdrawal of the antipsychotic agents (as can occur in the perioperative period) can lead to withdrawal dyskinesia that may signal the onset of TD. • No pharmacologic treatment has been shown to be completely effective in treating TD. Tetrabenazine (Xenazine®) is a dopamine depleting agent and is suggested for treatment of TD. Tetrabenazine was approved in the US in 2008 as an orphan drug for treatment of chorea associated with Huntington’s disease. The patient and a provider must complete a treatment form and send to the company. Once approved, the patient is assigned to one of four specialty pharmacies for dispensing. • Reserpine, a catecholamine depleting agent, has been used to treat refractory cases of choreatic TD. • Treatment with Vitamin E has been thought to attenuate symptoms of TD when given early in the course of disease. This effect is thought to be due to the antioxidant properties of Vitamin E. A 2007 meta-analysis revealed no significant improvement; however, those who were assigned to the placebo groups showed more deterioration in their symptoms. • Treatment of TD is usually unsatisfactory and prevention of the disorder is best accomplished by judicious use of antipsychotic medications known to cause TD. Likewise, frequent reassessments of the need for these drugs are recommended, and the lowest dose possible should be used to achieve the desired response.

TETRALOGY OF FALLOT A. Katharina Beckmann, MD James D. Boone, MD

BASICS DESCRIPTION

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. It is characterized by • Right ventricular outflow tract (RVOT) obstruction due to pulmonary valve stenosis or a dynamic subvalvular (infundibular) obstruction • Ventricular septal defect (VSD) • Deviation of the aorta to the right, overriding the right ventricle (RV) and left ventricle (LV) • Concentric right ventricular hypertrophy

EPIDEMIOLOGY Prevalence

• Live births: 3 in 10,000 • Occurs equally in males and females

Prevalence

Comprises 3.5–8% of all congenital heart diseases Morbidity

The morbidity depends on the severity of the right-to-left (R-to-L) shunt and on other organ dysfunction resulting from chronic heart failure and hypoxemia. Mortality

• After the first year of life: 25% • Four years of age: 40% • Ten years of age: 70% • Forty years of age: 95%

ETIOLOGY/RISK FACTORS

• Multifactorial • Untreated maternal diabetes • Phenylketonuria • Intake of retinoic acid • Trisomies 21, 18, 13 • Microdeletion of chromosome 22

PHYSIOLOGY/PATHOPHYSIOLOGY

• When the LV pressures exceed the RV pressures, flow across the VSD is L-to-R, and patients can be asymptomatic. However, when the RV pressures exceed the LV pressures, deoxygenated blood shunts across the intraventricular septum, causing systemic hypoxemia. The severity of disease is determined by the amount of R-to-L shunting, which is in turn dependent on ventricular pressure differences and the degree of RVOT obstruction. – Acidosis, hypoxemia and hypercarbia can all cause an increase in PVR, contributing to a detrimental increase in RV pressure. • Newborns are rarely cyanotic at birth unless the RVOT is atretic, leading to a mandatory Rto-L shunt. R-to-L shunt and cyanosis may not develop for several months; with time, the increase in pulmonary blood flow (from L-to-R shunting) can lead to significantly increased pulmonary pressures. – Can result in myocardial ischemia. This can lead to a drop in cardiac output with possible circulatory collapse or death. • Tet spells (hypercyanotic spells) are paroxysmal episodes of arterial hypoxemia that result from a decrease in SVR or increase in pulmonary vascular resistance (PVR) (favor R-to-L shunt). It presents as cyanosis, tachypnea, and possibly neurologic compromise. Tet spells: – Occur in 20–70% of patients and peak at the age of 2–3 months. – Are usually proceeded by agitation, crying, feeding, defecation, or any increase in physical activity. – Can result in transient cerebral ischemia causing paleness, limpness, and even unconsciousness. – The squatting (or knee-chest) position is one of the treatments for Tet spells because it compresses the femoral arteries and increases SVR, reducing the R-to-L shunt. • The RVOT obstruction can have a dynamic component (muscular) that contracts in response to inotropic stimuli. Therefore, increased contractility and tachycardia during times of stimulation or stress can worsen the pulmonary stenosis, causing increased R-to-L shunting and cyanosis. • Acidosis, hypoxemia and hypercarbia can all cause an increase in PVR, contributing to a detrimental increase in RV pressure.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• A clear understanding and appreciation of the patient’s anatomy is crucial in developing a rational, appropriate plan. • Avoid agitation, hypovolemia, acidosis, excessive crying, anxiety, and increased airway pressures. • Give premedication to ensure sufficient anxiolysis but avoid oversedation and resulting respiratory acidosis, which can increase PVR. • Maintain SVR and treat hypotension with phenylephrine and/or volume infusion. • Avoid drugs with beta-agonist properties as they may worsen infundibular spasm. • Recognize and treat Tet spells with volume infusion and/or phenylephrine, increasing the depth of anesthesia, and/or decreasing stimulation.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Mild-to-moderate cyanosis in the neonatal period without respiratory distress • Hypercyanotic Tet spells with a sudden decrease in oxygen saturation due to complete or near complete obstruction of RVOT • Poor weight gain, failure to thrive in children

History

• Prenatal testing • Perinatal history • Other congenital anomalies • Development/milestones in children • Ask for signs of cyanosis (Tet spells, clubbing) and frequency of occurrence • Exercise tolerance

Signs/Physical Exam

• Normal S1, single loud S2 (secondary to more anteriorly located aorta) • Systolic ejection murmur at left upper sternal border (due to RVOT) • Clubbing, perioral cyanosis • Check pulse oximetry. A normal saturation should be between 90% and 100% unless the patient is actively shunting from R-to-L (e.g., Tet spell). TREATMENT HISTORY

• Surgical correction by closure of the VSD and relief of the RVOT obstruction. RVOT dilation may result in QRS prolongation and ventricular arrhythmias, as well as pulmonary regurgitation with resultant RV hypertrophy and dysfunction. • Palliative surgery with a Blalock–Taussig shunt diverts blood flow from the left subclavian artery to the pulmonary artery (PA) to bypass the pulmonary stenosis. MEDICATIONS

• Prostaglandins may be used in neonates to preserve ductal patency postpartum if infundibular obstruction is severe and stable blood flow to the lungs is needed. Blood then flows directly from the aorta to the PA, bypassing the pulmonary obstruction. • Heart failure medications • Beta-blockers

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC. Polycythemia may develop from chronic arterial hypoxemia • Coagulation studies. Liver congestion may result in coagulopathy • ECG (right axis deviation, RVH) • Chest x-ray (CXR). Assess for right aortic arch, decreased pulmonary vascular markings, boot shaped heart • Echocardiography • CT angiogram, cardiac MRI • Cardiac catheterization (not indicated unless multiple VSDs, or abnormalities with the PA or coronary anatomy are present)

CONCOMITANT ORGAN DYSFUNCTION

• Cardiac: Severe tricuspid regurgitation, right heart failure, biventricular heart failure • Pulmonary: Edema, hypoxia, cyanosis, pulmonary hypertension • Hepatic: Congestion and impaired coagulation • Hematologic: Polycythemia form chronic hypoxemia; can cause thrombosis, endocarditis, strokes, and multiorgan dysfunction

CIRCUMSTANCES TO DELAY/CONDITIONS • Fulminant heart failure • Severe dehydration • Severe hypoxemia • Arrhythmias

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines and opioids should be carefully titrated to avoid oversedation and hypercarbia (can increase PVR). Consider avoiding intramuscular injections, which can lead to agitation and a possible Tet spell. • May want to avoid anticholinergics as tachycardia can narrow the RVOT, increase the R-to-L shunt, and lead to hypoxemia. • Endocarditis prophylaxis for dental procedures. • Assess volume status. Hypovolemia can exacerbate the RVOT obstruction. In patients with polycythemia from chronic hypoxemia, a prolonged NPO period can increase blood viscosity and lead to sludging. In severe cases, preoperative phlebotomy might be indicated. Special Concerns for Informed Consent Parental consent if a minor INTRAOPERATIVE CARE Choice of Anesthesia

• Individualize based on the patient and surgical procedure. • May want to avoid spinal anesthesia as this could lead to an undesirable drop in SVR.

Monitors

• Standard ASA monitors • In a pediatric patient with a patent ductus arteriosus two pulse oximeters should be placed to monitor a preductal (right hand) and a postductal (lower extremity) saturation. • Arterial line may be appropriate to monitor the PaO2 • Consider central line, PA catheter, and/or transesophageal echocardiography for high-risk surgeries (intraperitoneal and/or intrathoracic cardiac and noncardiac surgeries).

Induction/Airway Management

• Prior to induction, ensure euvolemia. Consider IV fluid bolus. • If an IV is present, etomidate or ketamine induction allows maintenance of the SVR. A mask induction may be appropriate in patients without an IV in situ or milder degrees of shunting. Systemic oxygenation and BP must be carefully monitored. High doses of volatile agents can cause detrimental decreases in SVR. • Hypotension on induction should be promptly treated with an IV fluid bolus and/or vasopressors. An alpha agonist such as phenylephrine is preferred because of the beneficial effects on SVR. • Opioids can be useful to blunt sympathetic response from intubation or surgical stimulation. • Nondepolarizing muscle relaxants can be used for paralysis, but histamine releasing muscle relaxants should be avoided to prevent a drop in the SVR. The chronotropic effects of pancuronium may be helpful in maintaining cardiac output. • Avoid a sympathetic surge with intubation (increases contractility) by ensuring that the patient is deep. The airway should be secured quickly in order to avoid hypoxemia and hypercarbia. • Any kind of airway obstruction can trigger a Tet spell. Hypercarbia and hypoxemia increase PVR and R-to-L shunting. A vicious cycle of further desaturations and decreased pulmonary blood flow can develop.

Maintenance

• Maintenance can be achieved with any inhalational agent as long as SVR and BP are maintained. • Alternatively nitrous oxide can be combined with ketamine; this combination maintains BP and SVR well. • Opioids and benzodiazepines can also be used but should be carefully administered to avoid a decrease in BP and SVR. Morphine should be used with caution due to its potential for histamine release. • Controlled ventilation is usually appropriate to maintain normocapnia. Excessive positive airway pressures can adversely increase the resistance to blood flow through the lungs. • Take meticulous care to avoid any infusion of air, which can lead to systemic air embolization (especially if nitrous oxide is used). If infusion of air is suspected, increase the FiO2 to 1.0 (turn the nitrous oxide off immediately to avoid an increase in bubble size).

• Maintain hemodynamic goals: – Deep anesthetic state to avoid sympathetic surges – Normal/high SVR to avoid “emptying” of the heart – Maintain adequate intravascular volume and treat hypotension aggressively with IV fluid boluses and vasopressors – Low PVR to avoid R-to-L shunting • Avoid hypothermia because this can lead to an increase in PVR and cause a R-to-L shunt.

Extubation/Emergence

• Before emergence, ensure adequate analgesia. • Tachycardia can be treated with short acting beta-blockers such as esmolol.

• Awake extubation can help avoid hypercarbia and hypoxemia; however, coughing and bucking on the endotracheal tube is also not desired.

FOLLOW-UP BED ACUITY

• Monitored bed with pulse oximetry • Consider ICU for high-risk patients

Medication/Lab studies/Consults COMPLICATIONS

• Right heart failure from volume overload • Biventricular dysfunction • Severe hypoxemia

REFERENCES

1. Apitz C, et al.Tetralogy of Fallot. Lancet. 2009;374(9699):1462–1471.

2. Bailliard F, et al.Tetralogy of Fallot, review. Orphanet J Rare Dis. 2009;13(4):2.

3. Fox D, et al.When “blue babies” grow up: What you need to know about tetralogy of Fallot. Cleve Clin J Med. 2010;77(11):821–828. 4. Schaff H, et al.Anesthetic management for transurethral resection of bladder in a 74-yearold man with uncorrected tetralogy of Fallot. J Clin Anesth. 2005;17(3):155–157. 5. www.mayoclinic.org/tetralogy-of-fallot See Also (Topic, Algorithm, Electronic Media Element) • Pediatric cardiac physiology • Shunt • Patent ductus arteriosus

CODES ICD9 745.2 ICD10 Q21.3 Tetralogy of Fallot

CLINICAL PEARLS

• Minimize R-to-L shunt by keeping the SVR high, maintaining intravascular volume, and keeping the PVR low (avoid hypercarbia, hypoxia, hypothermia, and acidosis). • Avoidance and treatment of Tet spells.

THALASSEMIAS Jeremy Wong, MD

BASICS DESCRIPTION

• Thalassemia is an autosomal-recessive hemolytic disorder caused by a decrease or absence of globin chain synthesis. It is classified as either α or β depending on the globin chain that is affected. Its manifestations are mostly secondary to anemia, iron overload, effects of chelation therapy, and thrombosis. • In contrast, sickle cell anemia and other hemoglobinopathies are characterized by the synthesis of dysfunctional globin proteins. EPIDEMIOLOGY Prevalence

Major thalassemia: ∼56,000/year are born with the disease worldwide Prevalence

• Among the most common genetic disorders, affecting 15 million people worldwide. Thalassemia trait may provide a degree of protection against malaria, thus explaining its genetic prevalence in tropical and subtropical regions. • β-thalassemia: >1% of people in the Mediterranean, India, Southeast Asia, North Africa, and Indonesia. • α-thalassemia: Found in 5–10% of people in the Mediterranean, 20–30% in West Africa, and ∼68% in South Pacific. Morbidity

• Usually related to anemia and its treatment: Splenomegaly, splenectomy, or blood transfusion. • Significant morbidity also occurs from liver disease, chronic infection, organ damage from iron overload, and complications from chelation therapy (cataracts, deafness, infection). Mortality

Worldwide: 3.4% of deaths in children <5 years ETIOLOGY/RISK FACTORS

Autosomal-recessive genetic inheritance PHYSIOLOGY/PATHOPHYSIOLOGY

• In all thalassemias, imbalanced globin chain synthesis causes a disruption of the normal 1:1 ratio of α and non-α chains. The defective red blood cells (RBCs) and their precursors are detected by the immune system and destroyed/hemolyzed.

– In β-thalassemias (defect in β chain synthesis), excess α chains precipitate in RBC precursors, damaging the membrane and leading to cell destruction (disrupted erythropoiesis). Cells that survive are released into the circulation, but they are subject to hemolysis. To compensate for the anemia, there is increased production of fetal hemoglobin (HbF) because the free α chains can bind with γ chains (Note: Has a higher O2 affinity).

– In α-thalassemias (defect in α chain synthesis), the excess γ chains (early in life) or β chains (later in life) are relatively soluble and able to form viable, soluble homotetramers. Hb Bart is comprised of 4γ chains and HbH is comprised of 4β chains. • Severe anemia stimulates erythropoietin production and expansion of extramedullary marrow in the thorax, head, and paraspinal regions. This leads to deformations of the face and skull as well as osteopenia. Neuropathy can be present due to nerve compression by large extramedullary hematopoietic masses. • Iron overload is associated with increased bleeding, susceptibility to infection, organ dysfunction (including left ventricular (LV) dysfunction and myocarditis), and endocrinopathies (diabetes, thyroid, adrenal disorders). In transfused patients, a heavy iron turnover is seen. In nontransfused patients, iron overload is the result of increased GI absorption, possibly to compensate for ineffective erythropoiesis. • Splenomegaly can result from the unusually large numbers of abnormal RBCs processed by the spleen. • Thrombotic tendency, pulmonary hypertension, leg ulcerations, priapism, and stroke may be a result of endothelial dysfunction due to the decreased bioavailability of nitric oxide (NO).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Common surgical procedures include splenectomy, cholecystectomy, line placement, osteotomies for bony deformities, and repair of fractured bones. • Special care must be taken to anticipate difficult airways in patients with abnormal maxillofacial anatomy. • Potential blood loss must be anticipated in the setting of baseline anemia. • Because of the risk for thrombosis, perioperative prophylaxis should be considered, and complications recognized and treated as needed.

Pregnancy Considerations

• In pregnant women with thalassemia, the Hb levels should be maintained above 10 g/dL in order to reduce the high reported rate of spontaneous abortion, intrauterine growth restriction, prematurity, as well as suppress hyperactive erythropoiesis in the mother. • Deferoxamine, if taken, is usually discontinued due to possible teratogenic effects. Of note, pregnancy, itself, may be an iron chelator due to hemodilution and fetal consumption of free iron. • Caesarean delivery is usually planned in order to reduce the cardiovascular stress associated with labor (especially in patients with compromised LV function) and to avoid complications of cephalopelvic disproportion due to small stature that is commonly seen in thalassemics.

PREOPERATIVE ASSESSMENT SYMPTOMS

Fatigue, weakness, fevers, loss of appetite/weight loss, shortness of breath History

• α-thalassemia: Mild or moderate forms demonstrate hematologic abnormalities at birth • β-thalassemia major is usually diagnosed in the latter part of the first year of life (but can appear as late as age 3–5 years) after the body converts from HbF to HbA production (γ chain production stops).

Signs/Physical Exam

Pallor, jaundice, hepatosplenomegaly, failure to thrive, bony deformities including frontal bossing, prominent facial bones, dental malocclusion (“chipmunk facies”), neuropathy, heart murmur, signs of congestive heart failure. TREATMENT HISTORY

• Patients with severe thalassemia require regular blood transfusion in combination with wellmonitored chelation therapy. The goal is to maintain an Hb value of at least 9–9.5 g/dL. Units should be leukocyte poor. • Splenectomy may be indicated for those with hypersplenism who require excessive blood transfusions or who develop bleeding due to thrombocytopenia • For select patients, stem cell transplantation is indicated. This is the only curative therapy available. If successful, no blood transfusions are required, but patients may still require chelation therapy.

MEDICATIONS

• Deferoxamine (chelating agent). Delays or prevents onset of cardiac disease. 30–40 mg/kg/day by subcutaneous infusion over 8–12 hours for 5 days/week, with IV supplementation as needed. Usually started 1–2 years after transfusions are initiated. • Vitamin E (antioxidant given for iron overload) • Folic acid to replenish stores that may be depleted from high cell turnover. • Aspirin for thromboprophylaxis.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC. In severe thalassemia, Hb often ranges from 2 to 8 g/dL, and MCV and MCH are usually very low. WBC count is often elevated in β-thalassemia major. Platelet count is usually normal unless there is marked splenomegaly. Peripheral blood smear shows marked hypochromasia and microcytosis. • Serum iron levels are elevated, with saturation as high as 80%. Serum ferritin level is high. • Skeletal imaging may show classic bone changes, osteopenia, and fractures. • MRI and CT can be used to evaluate large extramedullary tumor-like masses, or iron overload in the liver and heart (monitor response to chelation therapy). Liver biopsy may

also be performed. • ECG and echocardiogram may be indicated to evaluate cardiac function and iron overload.

CONCOMITANT ORGAN DYSFUNCTION

• Cardiopulmonary: Arrhythmias, pericarditis, CHF, pulmonary hypertension • GI: Hepatomegaly, cirrhosis • Hematologic: Infection, splenomegaly, thrombosis • Endocrine: Diabetes, thyroid dysfunction, adrenal dysfunction • Skeletal: Osteoporosis, fractures, osteonecrosis, maxillary hyperplasia, hypertelorism • Neurologic: Paresthesia, paralysis, hearing loss, vision loss

CIRCUMSTANCES TO DELAY/CONDITIONS

Evidence of cardiopulmonary compromise or significant endocrine dysfunction should delay elective procedures to allow for further workup and optimization. CLASSIFICATIONS

• α-thalassemias result from a deficiency or deletion of one or more of the 4α genes (2 from each parent). – Clinically silent carrier state: No symptoms, but may have mild microcytic, hypochromic anemia. – α-thalassemia trait: Deletion of 2α genes causes a mild hypochromic anemia. – α-thalassemia intermedia (Hemoglobin H disease): Deletion of 3α genes leads to moderately severe hemolytic anemia, hepatosplenomegaly, jaundice, and vasculopathy; patients may require occasional or frequent transfusions depending on severity of disease. – α-thalassemia major: Deletion of all 4α genes causes HbF Bart’s disease (hydrops fetalis syndrome, unless intrauterine blood transfusions given). • β-thalassemias result from a deficiency or deletion of one or more of the 4β genes (2 from each parent) – Clinically silent carrier state: No symptoms, but can have a mild microcytic, hypochromic anemia – β-thalassemia trait: Deletion of 2β genes causes anemia, marked hypochromia and microcytosis, elevated Hb A2, HbF, or both. – β-thalassemia intermedia: Deletion of 3β genes leads to severe anemia, but are not typically transfusion dependent due to a compound heterozygote state. – β-thalassemia major: Deletion of all 4β genes causes Cooley’s anemia (transfusion dependent anemia, massive splenomegaly, craniofacial abnormalities, growth retardation). • β-thalassemia associated with β chain structural variants: Coinheritance with HbE results in HbE/β thalassemia, which may cause clinical anemia varying in severity from thalassemia intermedia to thalassemia major.

TREATMENT PREOPERATIVE PREPARATION

Premedications

• Prophylactic antibiotics, particularly in patients who have had a splenectomy. • RBC transfusion, if appropriate • Thromboprophylaxis, as appropriate.

Special Concerns for Informed Consent

Blood consent should be discussed given the higher likelihood of anemia and need for transfusion. INTRAOPERATIVE CARE Choice of Anesthesia

• Anesthetic literature is scant, but both regional and general anesthesia are probably safe as long as thrombocytopenia is not present. • Spine abnormalities due to osteoporosis may make neuraxial anesthesia more difficult.

Monitors

• Standard ASA monitors • Invasive monitoring may be indicated, depending on the operation and presence of cardiac dysfunction.

Induction/Airway Management

Bony abnormalities of the maxillofacial area may make intubation difficult. Have difficult airway equipment nearby and/or ready. Maintenance

• Balanced anesthetic techniques that minimize cardiovascular depression are especially important. Cardiac output should be maintained to ensure optimal peripheral oxygen delivery in patients with significant anemia. • Blood transfusion should be performed with leukocyte reduced red cells. • Cell salvage has been successfully used to manage blood loss. Successful cardiopulmonary bypass in patients with Hemoglobin H has also been described.

Extubation/Emergence

No specific considerations, unless difficult airway is present.

FOLLOW-UP BED ACUITY

Depending on the degree of organ dysfunction and nature of surgery, an ICU bed may be warranted. MEDICATIONS/LAB STUDIES/CONSULTS

• Restart deferoxamine as soon as possible if discontinued preoperatively. • Transfusion-dependent patients should have frequent blood counts and transfusions as

needed to maintain target values. • Serum ferritin levels are often used as a marker for hepatic and macrophage iron stores in order to guide chelation therapy. • For patients with severe disease, a hematology consultation is recommended to aid with perioperative management. COMPLICATIONS

Primarily involves airway complications, congestive heart failure, transfusion reactions, and thrombosis.

REFERENCES

1. Butwick A, Findley I, Wonke B. Management of pregnancy in a patient with thalassemia major. Int J Obstet Anesth. 2005;14(4):351–354. 2. Firth P. Anesthesia and hemoglobinopathies. Anesthesiology Clin. 2009;27:321–336. 3. Morris CR. Mechanisms of vasculopathy in sickle cell disease and thalassemia. Hematology. 2008;1:177–185. 4. Vichinsky E. Changing patterns of thalassemia worldwide. Cooley’s Anemia: Eighth Symposium. Annals of the New York Academy of Sciences. 2005;1054:18–24. 5. http://emedicine.medscape.com/article/958850-overview\ See Also (Topic, Algorithm, Electronic Media Element) • Hemoglobin • Anemia • Hemolytic anemia

CODES ICD9 • 282.40 • 282.43 α thalassemia • 282.44 β thalassemia ICD10 • D56.0 α thalassemia • D56.1 β thalassemia • D56.9 Thalassemia, unspecified

CLINICAL PEARLS

• Patients with thalassemia may have concomitant organ dysfunction that can complicate anesthetic management, including heart failure, arrhythmia, pulmonary hypertension, and splenomegaly. • Extramedullary bone expansion may lead to changes in airway anatomy that can make

intubation difficult. • Patients with thalassemia may have increased risk for thrombosis, especially if splenectomized. • Chelation therapy and regular blood transfusions are important tools in the management of significant thalassemias.

THE ADDICTED ANESTHESIA CARE PROVIDER Ethan O. Bryson, MD

BASICS DESCRIPTION

• Opioid addiction represents a major issue in the anesthesia workplace, so much so that some have called it an occupational hazard. • Alcoholism and addiction to other substances impact anesthesia care providers at rates similar to other professions. • The drug of choice for anesthesia care providers entering treatment is typically an opioid, usually fentanyl. • There is an association between chemical dependence and mental illness. Successful treatment for addiction requires treatment of comorbid psychopathology. • Participation in self-help groups is considered a vital component in the therapy of the impaired healthcare provider. EPIDEMIOLOGY Incidence

• The incidence of drug abuse among anesthesia care providers as indicated by referral to treatment centers is between 1% (for attending physicians) and 2% (for residents and cRNAs). • The incidence of drug abuse as indicated by anonymous self-reporting is upwards of 10%.

Prevalence

• Drug abuse is at least as prevalent among anesthesia care providers as it is among the general population, and tends to mirror the community prevalence. • The prevalence of alcohol and other drug abuse over the course of the anesthesia care provider’s career is 12–15%. Morbidity

• The addicted anesthesia care provider may develop hypersensitivity to physical stimuli including allodynia in addition to developing tolerance. • These individuals are at increased risk for developing blood-borne viral infections such as HIV, hepatitis C virus (HCV) and hepatitis B virus (HBV). • Chronic injection can lead to soft tissue infections. • They are also at risk for drug overdose and drug dependence, and may also have associated mental health problems. Mortality

The risk of drug-related death among anesthesia care providers is highest in the first 5 years after training and remains increased over that of other healthcare providers.

ETIOLOGY/RISK FACTORS

• Occupational exposures to drugs of abuse that sensitize the reward pathways in the brain may promote substance use by physically altering the brain’s chemistry. • Many genes have been identified as being associated with the susceptibility to drug addiction and traits associated with risk taking behavior. • While most individuals who experiment with drugs do not become dependent; individuals who exhibit traits such as novelty-seeking and antisocial behavior are at higher risk for developing addiction. • In some cases self-administration of drugs of abuse may indicate an attempt to self-medicate the symptoms associated with psychiatric illness. • Emotional stress coupled with physical exhaustion and access to drugs of abuse may trigger addiction in susceptible individuals.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Dopamine release in the mesolimbic system of the brain reinforces drug-seeking behaviors associated with several drugs of abuse. • Drugs of abuse physically alter the chemistry of the addicted brain. Alterations in the relative levels of GABA, dopamine, and serotonin (neurotransmitters associated with reward pathways) favor drug-seeking behavior.

PREVENTATIVE MEASURES

• A contributing cause of addiction in anesthesia care providers is the easy access to opioids and other psychoactive medications. Tighter control allows for earlier detection and documentation in suspected cases of abuse. • Anesthesia information management systems can be used to identify patterns suspicious for diversion among anesthesia personnel. • Wasted medications should be returned to the pharmacy and analyzed to verify content. • Random drug screening has been proposed as a deterrent, but most nonmilitary hospitals do not employ such practices. • Education regarding the risk for addiction in anesthesia care providers as well as the signs and symptoms associated with the disease is very important.

DIAGNOSIS • Because the addicted anesthesia care provider needs to remain close to their drug of choice, they may appear quite functional until late in the disease. • There is no specific pattern of behavior that suggests addiction; it can be as minimal as a change in behavior over a short period of time. Changes typically seen in the addicted anesthesia care provider include the following: – Withdrawal from family, friends, and leisure activities – Mood swings, with periods of depression alternating with periods of euphoria – Increased episodes of anger, irritability, and hostility – Spending more time at the hospital, even when off duty – Volunteering for extra call

– Refusing relief for lunch or coffee breaks – Requesting frequent bathroom breaks – Signing out increasing amounts of narcotics or quantities inappropriate for the given case – Weight loss and pale skin • The addicted individual is often the last to recognize that a problem exists. • It is important that relatives, friends, and coworkers gain a clear understanding of the disease and understand what to do if they suspect addiction.

DIFFERENTIAL DIAGNOSIS

• The anesthesia care provider who exhibits some of the signs and symptoms above may not, in fact, be diverting and abusing drugs. • Other possibilities include – Trying to establish oneself in the group practice – Attempting to increase personal income – Coexisting mental illness

TREATMENT Once an anesthesia care provider has been identified as requiring treatment for addiction, a referral is made to an inpatient facility that specializes in the treatment of healthcare providers. • It is important for recovery that the affected individual develops the support of other similarly affected healthcare providers. • Treatment involves detoxification, monitored abstinence, intensive education, exposure to self-help groups, and psychotherapy. • Individual and group therapy sessions attempt to alter addictive behaviors. The length of inpatient stay for this initial treatment lasts anywhere from 8 weeks to 3 months and in cases of relapse may require a 12-month stay.

FOLLOW-UP • State medical societies are allowed to enroll addicted healthcare providers into diversion programs designed to rehabilitate the affected individual and return them to practice. The addicted anesthesia care provider is allowed to return to clinical practice only under close supervision. • The length of post-treatment monitoring contracts are at least 5 years. The contracts mandate regular random collection of urine and/or hair samples for evidence of drug use as well as participation in facilitated group and individual therapy and anonymous 12-step programs. • Return to work should be in a graded fashion so that the anesthesia care provider has adequate time to attend to recovery-related obligations and is not overwhelmed by clinical duties. Duties may be gradually increased on a set schedule that can be adjusted after consulting with the worksite monitor and therapist. • The risk of relapse is increased in individuals with a family history of addiction or coexisting

mental illness. Such persons should be advised to strongly consider retraining in another medical field with less access to the major opioids.

CLOSED CLAIMS DATA

In a review of 2,715 claims in the database, only 7 mention substance abuse as possibly playing a role in malpractice litigation against anesthesiologists.

REFERENCES

1. Booth JV, Grossman D, Moore J, et al. Substance abuse among physicians: A survey of academic anesthesiology programs. Anesth Analg. 2002;(95):1024–1030.

2. Bryson EO, Silverstein JH. Addiction and substance abuse in anesthesiology. Anesthesiology. 2008;109(5):905–917. 3. Bryson EO, Hamza H. The drug seeking anesthesia provider. Int Anesthesiol Clin. 2011;49(1):157–171. 4. Bryson EO, Frost EAM (Eds). Perioperative Addiction. New York, NY: Springer Science and Business Media, 2011. See Also (Topic, Algorithm, Electronic Media Element) • Alcohol abuse

CLINICAL PEARLS

• The most common drug abused by anesthesia care providers is fentanyl. • If a colleague is suspected of abusing drugs or alcohol, the issue should be taken to the state’s physician or nursing health program. • Addiction is a chronic, relapsing disease. There is no cure but patients can be successfully managed with a variety of treatment modalities. • Legal issues – Not bringing an affected individual to the attention of those who can help may leave people open to legal liability if the impaired anesthesia care provider subsequently injures a patient. – Not all states have mandatory reporting laws; familiarization with the state’s specific expectations should be made. – In the event that the state does not mandate that impaired providers are reported, this should not preclude one from filing a complaint. – If you have first-hand knowledge of provider impairment, you have an ethical obligation to report it in order to protect the public and to get the individual the help that they need.

THORACIC ANEURYSM REPAIR Alina M. Grigoire, MD, MHS, FASE Ileana Gheorghiu, MD

BASICS DESCRIPTION General

• A thoracic aortic aneurysm (TAA) is a permanent, localized dilation that is at least 1.5 times the diameter of the expected normal value. Classifications are based on the anatomic location and extent of involvement (Crawford, Debakey, and Stanford). • Surgical repair often implements partial left heart bypass (LHBP) or femoral-femoral (femfem) cardiopulmonary bypass (with selective cerebral perfusion and deep hypothermic circulatory arrest [DHCA]) when the aneurysm is located at the ascending aorta or arch; there is proximal involvement of structures (aortic valve, annulus, sinuses of Valsalva, etc.); it is large in size; or repair is anticipated to be complex or require a long cross-clamp time. These techniques decrease hemodynamic stability and spinal cord ischemia/ paralysis. In select cases (e.g., descending aneurysms), repair may be considered without LHBP or femfem bypass. • Following surgical exposure, partial or full heparinization is administered, bypass techniques are implemented, and the aorta is cross-clamped both distal and proximal to the aneurysm. The aneurysm is opened and repaired typically with a Dacron graft. This is followed by declamping, reperfusion, adequate hemostasis, and closure. • Open surgical repair involves surgical exposure, followed by partial or full heparinization and partial left heart bypass (LHBP) or femoral-femoral (fem-fem) cardiopulmonary bypass (CPB). The aorta is cross-clamped both proximal and distal to the aneurysmal segment, the aneurysm opened and repaired with Dacron graft. This is followed by declamping, reperfusion, adequate hemostasis, and closure. • Endovascular repair has become a popular approach; it provides the benefit of a less invasive surgical technique with faster recovery and better short-term outcomes. Position

Right (R) lateral decubitus with hips rotated toward a more supine position. Incision

• Left (L) lateral thoracic • Median sternotomy for CPB with deep hypothermic circulatory arrest (DHCA) technique

Approximate Time

4–5 hours average, depending on surgical experience EBL Expected

500–1,500 mL blood loss, dependent on surgical experience Hospital Stay 5–10 days

Special Equipment for Surgery

• Partial LHBP with selective organ perfusion. • Fem-fem CPB with DHCA and selective cerebral perfusion.

EPIDEMIOLOGY Prevalence

• No current feasible screening technique • 10.4/100,000 person/years; equal in both sexes • Ascending aorta 51%, aortic arch 11%, descending aorta 38% • Average growth of 0.07 cm/year in ascending aorta and 0.19 cm/year in descending aorta. Growth rate >1 cm/year is an indication for elective surgical repair.

Prevalence

400/100,000 autopsies by the age of 65. Morbidity

• Cumulative risk of rupture is 20% at 5 years. • Risk factors for rupture: Female, elevated diastolic pressure, aneurysm >5 cm, obstructive pulmonary disease.

Mortality

• 27.4% overall in-hospital mortality for acute aortic dissection • Type A: 26% surgical management and 58% medical management. Type B: 31.4% surgical management and 10.7% medical management

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Hemodynamic (HD) instability is very common in the presence of dissecting aneurysms (cardiac tamponade, ongoing hemorrhage, myocardial ischemia, organ malperfusion). • Repair involves significant HD changes such as massive blood loss, drop in preload, acute increase in afterload with cross-clamping, and myocardial depression. • Neuroprotection techniques can include a spinal drain, neurophysiologic monitoring, and electroencephalogram (EEG) for DHCA technique.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Enlargement: Hoarseness (recurrent laryngeal nerve compression), dysphagia, plethora and edema, congestive heart failure (CHF), pain (neck, jaw, precordial, interscapular). • Dissection/rupture: Hemiparesis, hemiplegia, HD instability, tamponade, respiratory distress, cardiogenic shock.

History

Most frequently diagnosed incidentally Signs/Physical Exam

Hypertension (HTN) or hypotension, syncope, altered mental status, superior vena cava syndrome, cardiac tamponade (pulsus paradoxus, jugular venous distension, Kussmaul’s sign), limb ischemia MEDICATIONS

• Beta-blockers: Decrease aortic wall tension and myocardial oxygen consumption, decrease perioperative morbidity and mortality, could augment preexisting left ventricular (LV) dysfunction. • Anticoagulant and antiplatelet medication: Impact the placement of spinal drains • Antihypertensives: Sodium nitroprusside and nitroglycerine (both have negative impact of spinal cord perfusion pressure (SCPP)); nicardipine is the drug of choice DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hg, WBC, platelet count/function, PT/PTT, INR, BUN/creatinine • CT/MRI angiography: 100% sensitivity, as well as assessment of the extension of aneurysms and airway involvement (distortion of L main stem bronchus). • Angiogram: Accurate diagnosis of the tear points, involvement of the artery of Adamkiewicz, dissection into other major arteries (great vessels, renal, mesenteric, common iliac arteries). • Carotid Doppler: Evaluate the extent of dissection into carotid arteries, rule out atherosclerotic plaques with potential risk for stroke during selective antegrade cerebral perfusion. • Pulmonary function tests for preexisting pulmonary disease, COPD, restrictive lung disease, previous lung resection to assess the feasibility of one lung ventilation. • Echocardiogram and dobutamine stress test for preexisting ischemic cardiomyopathy, coronary stents, pulmonary hypertension (PHTN), right ventricular dysfunction. CONCOMITANT ORGAN DYSFUNCTION

Cerebrovascular, coronary artery, pulmonary, renal, peripheral vascular disease

TREATMENT PREOPERATIVE PREPARATION Premedications

• Antihypertensive and antianginal medication should be continued, as appropriate. • Anxiolytics can minimize HTN and rupture.

Special Concerns for Informed Consent

• Emergency intervention for unstable cases/altered mental status

• Consent for blood transfusion • Potential for postoperative intubation • Potential for spinal cord injury and paralysis

Antibiotics/Common Organisms

Wide coverage of both gram (+) and (–) germs; Staphylococcus aureus, most common, followed by Salmonella. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with endotracheal tube (ETT) • Epidural anesthesia may also be used; however, it poses a higher risk for spinal cord hematoma and makes postoperative neurotesting more challenging.

Monitors

• Standard monitors and Foley catheter. • Preinduction radial arterial line (R side for descending aortic procedures, L side for ascending aorta and arch); femoral line after induction (R side for L thoracotomy with LHBP, L side for fem-fem CPB with DHCA technique). • Large-bore peripheral IVs and multiport central line. A rapid infusion system should be primed and connected. Consider a pulmonary artery catheter for preexisting LV dysfunction, pulmonary HTN. • Nasopharyngeal temperature (NPT) for brain temperature and bladder temperature (BT) for visceral temperature. • Spinal drain for monitoring CSF pressure and spinal cord protection. • Regional cerebral oximetry: Assessment of adequate, bilateral brain oxygenation during CPB with DHCA and selective cerebral perfusion. • BIS may be considered, particularly for LHBP or fem-fem bypass. • TEE: Confirmation of the extent and severity of aortic pathology, assessment of volume status, myocardial function, aortic valve function, adequate LV decompression during CPB with DHCA. • Neuromonitoring: MEP, SSEP, EEG for CPB with DHCA.

Induction/Airway Management

• Maintain HD stability and volume status • Double lumen tubes (DLT) are used to improve visualization for descending aneurysms; usually left-sided (consider a right DLT if the left mainstem bronchus is compressed or distorted). • Single lumen ETT for ascending aortic and arch surgery.

Maintenance

• LHBP technique is used for partial redistribution of blood from the upper to the lower body, reduction in afterload and myocardial O2 consumption, and improved SCPP. Heparinize to an activated clotting time of 300 s and maintain flows at 1,000–2,000 mL/min. • Fem-fem CPB with DHCA. Full heparinization, cool to 18°C, initiate DHCA after 20 min of

18°C core temperature, rewarm slowly with NPT-BT gradient ≤2°C • Spinal cord protection – Steroids can decrease spinal cord edema; mannitol can enhance free radical scavenging. – Lumbar drains may be placed for spinal cord protection when bypass techniques are not used. Spinal cord perfusion pressure is equal to the mean arterial pressure minus the intracranial pressure. CSF is drained in 10 mL aliquots when the lumbar CSF pressure exceeds 10 mm Hg; avoid draining >20 mL/hour. – Neuromonitoring. Avoid high levels of volatile agents and consider TIVA (propofol, fentanyl, remifentanil). Boluses should be avoided, particularly at critical times to avoid false positives. Avoid muscle relaxation, if possible; alternatively maintain 2–3 twitches when MEP monitoring is used (this should be discussed with the surgical and neuromonitoring team). • Avoid muscle relaxation, if possible; alternatively, maintain 2–3 twitches when MEP monitoring is used. • Spinal cord protection: SCPP = MAP – ICP. CSF is drained for lumbar CSF pressure >10 mm Hg in 10 mL aliquots; avoid draining >20 mL/hour. Steroids and mannitol decrease spinal cord edema and free radical scavenging. • Aortic clamping is associated with an acute increase in afterload, preload (secondary to volume redistribution), myocardial oxygen consumption, and ICP • Aortic unclamping is associated with hypotension from hypovolemia, accumulation of vasoactive substances, acidosis, hypocalcemia. • Coagulopathy is commonly encountered as the result of dilution, hypothermia, quantitative and qualitative platelet dysfunction, heparin effect, and fibrinolysis. Antifibrinolytic use is recommended.

Extubation/Emergence

If a DLT was utilized, should be carefully changed to a single lumen ETT (patient may have significant facial and laryngeal edema).

FOLLOW-UP BED ACUITY

• Intensive care unit • Maintain systolic blood pressure (SBP) >140 mm Hg for adequate SCPP • Avoid anticoagulants and antiplatelet medication for the first 48 hours.

ANALGESIA

• Significant pain • Local anesthetic infiltration at the incision site • Opioid/dexmedetomidine drip

COMPLICATIONS

• Bleeding, graft infection, heart attack, stroke, renal failure, bowel ischemia, respiratory

failure. • Spinal cord injury is multifactorial in etiology: Interruption of blood flow, spasm of the microcirculation, increased CSF, inadequate revascularization of the spinal arteries. – Increase SBP to >140 mm Hg or a MAP >90 mm Hg using vasopressors – Drain CSF to achieve a CSF pressure ≤10 mm Hg (maximum 20 mL/hr) – Consider steroids and magnesium. PROGNOSIS

5-year overall survival is 56%.

REFERENCES

1. Coselli JS,Conklin LD, LeMaire SA. Thoracoabdominal aortic aneurysms repair: Review and update of current strategies. Ann Thorac Surg. 2002;74:S1881–1884. 2. Coselli JS, Moreno PL. Descending and thoracoabdominal aneurysm. In Cohn LH, Edmunds LH Jr, eds. Cardiac Surgery in the Adult. New York: McGraw-Hill, 2003:1169–1190. 3. Crawfors ES, Coselli JS. Thoracoabdominal aneurysm surgery. Semin Thorac Cardiovasc Surg. 1991;3:300–322. 4. Davies RR, Gallo A, et al. Novel measurement of relative aortic size predicts rupture of thoracic aortic aneurysm. Ann Thorac Surg. 2008;85:S1–41. 5. Khan RD, Stone ME, et al. Anesthetic considerations for descending thoracic aortic aneurysms repair. Semin Cardiothorac Vasc Anesth. 2007;11:205–223. See Also (Topic, Algorithm, Electronic Media Element)

• Abdominal aortic aneurysm • Circulatory arrest • One lung ventilation • Somatosensory- and Motored-evoked potentials (SSEPs/MEPs) • Antifibrinolytics

CODES ICD9 • 441.2 Thoracic aneurysm without mention of rupture • 747.29 Other anomalies of aorta ICD10 • I71.2 Thoracic aortic aneurysm, without rupture • Q25.4 Other congenital malformations of aorta

CLINICAL PEARLS

• Maintain a low preload prior to cross-clamping. • If acute hypoxia occurs during one lung ventilation and aortic cross-clamp, consider asking

the surgeon to partially cross-clamp the left pulmonary artery to minimize blood being shunted to the unventilated left lung. • If the BP drops during LHBP and the TEE confirms normal LV function with an underfilled LV, decrease the LHBP flow to increase LV preload. • Acute HD instability could occur during aortic cross-clamping due to blood loss from the collateral circulation.

THROMBOCYTOPENIA Mona G. Sarkiss, MD, PhD

BASICS DESCRIPTION

• Thrombocytopenia is defined as a platelet count <150,000/μL; it can result from decreased production, increased destruction, dilution, and errors with measurement. The platelet count is not, by itself, a predictor of platelet function and perioperative bleeding. • Occasionally thrombocytopenia is associated with hypercoagulability and an increased risk of thrombosis. EPIDEMIOLOGY Prevalence

• Pseudothrombocytopenia: 0.2% in the general population, 1.9% in hospitalized patients, and 2% in patients taking abciximab. • Autoimmune thrombocytopenia (in the US): Adults less than 10 per 100,000 and children 1– 4 per 100,000. • Heparin-induced thrombocytopenia (HIT): Up to 8% of patients receiving heparin are at risk of developing antibodies to platelets; only 1–5% will progress to develop HIT with thrombocytopenia and one-third may suffer from arterial and/or venous thrombosis. • Gestational thrombocytopenia: Occurs in 5.8% of pregnancies and is not associated with increased risk of bleeding. • Preeclampsia related thrombocytopenia occurs in 50% of preeclamptic patients but clinical hemorrhage is uncommon.

ETIOLOGY/RISK FACTORS

• Impaired production: – Congenital – Acute leukemia, myelodysplasia – Osteoporosis – Toxins: Chemotherapy, alcohol – Infections: HIV – Radiotherapy • Increased intravascular destruction: – Autoimmune: Primary causes: Idiopathic thrombocytopenia, systemic lupus erythematous Secondary causes: Drug-induced (HIT), post-transfusion, neonatal autoimmune thrombocytopenia – Non-autoimmune: Disseminated intravascular coagulopathy (DIC) Thrombotic thrombocytopenic purpura (TTP)

Hemolytic uremic syndrome (HUS) Infection Preeclampsia/HELLP syndrome • Increased extravascular destruction: – Hypersplenism • Dilutional: – Massive transfusion • Pseudothrombocytopenia

PHYSIOLOGY/PATHOPHYSIOLOGY

• Idiopathic thrombocytopenia: Attachment of antibodies or immune complexes to platelets resulting in their premature removal from the circulation by the reticuloendothelial system. • Systemic lupus erythematous: Antiplatelet antibodies or circulating immune complexes bind to platelets. • HIT – HIT type 1: A benign, non-autoimmune condition. Mild thrombocytopenia occurs within 1–2 days after heparin therapy and resolves spontaneously within a few days even with continued heparin therapy. – HIT type II: IgG antibodies bind to heparin bound to platelet factor 4. Together, this IgG– heparin–PF4 complex binds to platelet receptors and activates them. Venous thrombosis occurs more commonly than arterial thrombosis. Occurs 5–10 days after the initiation of therapy. • Post-transfusion thrombocytopenia occurs about 10 days after a blood transfusion and is due to antibodies in the recipient against human platelet antigen 1a (HPA–1a) on transfused platelets. • Neonatal alloimmune thrombocytopenia (NAIT) results from transfer of maternal IgG antiplatelet antibodies across the placenta to the fetus. The antibody attaches to the HPA-1a inherited from the father and is lacking in the mother. Severe thrombocytopenia during the early phase of the second trimester can occur and may cause intracranial hemorrhage (20% incidence). • DIC results from an abnormal, systemic activation of the coagulation cascade. This leads to deposition of fibrin in the microcirculation and aggregation and "consumption" of platelets with consequent thrombosis causing ischemia and organ necrosis. The blood becomes “unclottable" and severe hemorrhage occurs. • TTP is due to an inability to cleave large multimers of von Willebrand factor (vWF). These large multimers bind to platelets and cause thrombosis of the small vessels. TTP may result in renal failure and impaired neurological function. • HUS is similar to TTP in that there is a failure of cleavage of large multimers of vWF. It is characterized by the acute onset of microangiopathic hemolytic anemia, renal injury, and a low platelet count. HUS can be triggered by infection (e.g., Escherichia coli and HIV), genetic predisposition, medication, and systemic diseases that cause microvascular injury (e.g., systemic lupus). • HELLP syndrome results in microvascular injury with endothelial cell damage along with progressive platelet activation and consumptive thrombocytopenia. • Infection. Viral (e.g., HIV, EBV, and CMV), rickettsial, and parasitic infections (e.g., malaria)

can reduce platelet production causing thrombocytopenia. Also sepsis in the critically ill is associated with an increase in macrophage colony-stimulating factor; it is responsible for histiocyte engulfment of megakaryocytes. • Splenomegaly. Up to 90% of platelets may be sequestered in the spleen but it is not usually associated with bleeding. • Dilutional thrombocytopenia can occur in patients who have received multiple units of whole blood or packed RBCs (pRBCs). Blood stored at 4°C for 24 hours has few viable functioning platelets (after 6 hours storage at 4%C, platelets lose 50–70% of their activity. • Pseudothrombocytopenia. Occurs due to in vitro agglutination of platelets by EDTA anticoagulant and can result in falsely low platelet counts being recorded with automated measurements. • Pregnancy associated thrombocytopenia is mild, asymptomatic, and present in 5% of pregnant women at term.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• A thrombocytopenic patient should be evaluated for the underlying cause, the possibility of qualitative platelet dysfunction, other coagulation defects, and signs and symptoms of impaired hemostasis. • Each unit of transfused platelets increases the platelet count by 10,000/μL assuming that there is no immediate sequestration and destruction by hypersplenism or dilution by IV fluids and pRBCs. • Ensure that the blood bank has a recent type and cross-match with pRBCs and platelets available and ready for immediate transfusion, if needed. Of note, cross-matching the recipient’s platelets with those of the donor is not necessary; however incompatibility can reduce post-transfusion counts.

PREOPERATIVE ASSESSMENT SYMPTOMS

Hematemesis, hemoptysis, hematochezia, melena History

• Easy bruising or bleeding gums • Medications that can cause impaired or decreased platelet counts • Malignancies and radiation

Signs/Physical Exam

• Bruising, petechiae, purpura of the skin conjunctiva or oral mucosa • Bleeding at venipuncture sites or petechiae at the BP cuff site.

TREATMENT HISTORY

Dependent on the etiology and severity • ITP: Steroids, IV immunoglobulin (IVIG), splenectomy • TTP, HUS: IVIG, plasmapheresis

• HIT: Discontinue heparin, consider alternative anticoagulant if blood thinning is still needed • Hypersplenism: Splenectomy

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• A manual platelet count is more accurate and reliable in patients with recent thrombocytopenia. • When pseudothrombocytopenia is suspected, counts should be repeated in citrateanticoagulated or heparin-anticoagulated blood samples. • Platelet function tests include – PFA-100 – Plateletworks analyzer – Thromboelastogram (TEG). Assesses the entire process of clot formation including platelet and coagulation factor function. – Aggregometry – Con and plate analyzer

CONCOMITANT ORGAN DYSFUNCTION

Depends on underlying cause and can include • Renal failure • Liver cirrhosis • Bone marrow failure • Anemia and hypovolemia • Thrombocytopenic thrombotic disorders may result in deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), and cerebrovascular accident (CVA) CIRCUMSTANCES TO DELAY/CONDITIONS

• For complex causes of thrombocytopenia, a hematology consult may be warranted to optimize the patient preoperatively and continue appropriate therapy intraoperatively and postoperatively. • Spontaneous bleeding occurs with platelet counts <20,000/μL (1). • Neurosurgery and ophthalmic surgery, where even minimal bleeding can have a deleterious effect, should be performed only with a platelet count ≥100,000/μL. • Major invasive surgery including cardiac surgery can be safely performed with platelet counts of 50,000/μL only if platelet function is normal and no other coagulation abnormalities exist (2). • Obstetrics patients with HELLP syndrome. Platelet transfusions should be considered when the count is <30,000/μL for vaginal delivery or <50,000/μL for Cesarean section (2). • Lumbar puncture for intrathecal chemotherapy should not be performed with platelet counts <20,000/μL (4).

CLASSIFICATIONS

• Impaired production • Increased destruction (intravascular or extravascular)

• Dilutional • Pseudothrombocytopenia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Preoperative platelet transfusion if the platelet count is <50,000/μL or active hemorrhage is present and surgery must be performed. • DDAVP 0.3 μg/kg IV in patients with renal failure or von Willebrand’s disease • A temporary increase in platelet count can be achieved with IVIG, plasma exchange, or corticosteroids, when appropriate.

Special Concerns for Informed Consent

Discuss the possibility of blood product transfusion INTRAOPERATIVE CARE Choice of Anesthesia

Spinal anesthesia requires a minimal platelet count of 50,000/μL while epidural anesthesia requires a minimal platelet count of 80,000/μL (2). When weighing the risks and benefits, coagulation profile should also be considered. Monitors

• Standard ASA monitors • Central line placement. Oozing from the site may occur if the platelet count is <50,000/μL (5).

Induction/Airway Management

Airway instrumentation should be performed gently due to the risk of mucosal bleeding. Consider lubricating the ETT and laryngoscope. Nasal intubation is relatively contraindicated. Maintenance

• Nasogastric tube placement should be avoided. • Volume status. Should be continuously assessed, due to the risk of bleeding. • Transfusion. pRBC and platelet transfusion, as needed.

Extubation/Emergence

• Vigilance with airway bleeding during extubation • Avoid nasal trumpet placement

FOLLOW-UP BED ACUITY

Depends on the surgical procedure, comorbidities, and intraoperative events (e.g., massive transfusion and ongoing bleeding). MEDICATIONS/LAB STUDIES/CONSULTS

• Corticosteroids, when appropriate, should be continued in the postoperative period. • Follow-up platelet counts • Hematology consult may be required

COMPLICATIONS

• Thrombocytopenia related – Postoperative bleeding – Bleeding or hematoma at IV, central line, and arterial line sites – Postoperative thrombosis: DVT, PE, MI, CVA • Platelet transfusion related – Alloimmunization can be minimized by using leukocyte-depleted platelet concentrates or HLA-matched platelets. – Graft-versus-host disease can be prevented by gamma-irradiation of platelet concentrates prior to transfusion in patients with immunodeficiencies (6). – Increased risk of disease transmission • Perioperative thrombosis: DVT, PE, MI, CVA.

REFERENCES

1. obas M.Preoperative assessment of coagulation disorders. Int Anesthesiol Clin. 2001;39(1):1–15. 2. Samama CM, Djoudi R, Lecompte T, et al. Perioperative platelet transfusion. Recommendations of the French Health Products Safety Agency (AFSSAPS) 2003. Minerva Anestesiol. 2006;72(6):447–452. 3. Spahn DR. Strategies for transfusion therapy. Best Pract Res Clin Anaesthesiol. 2004;18(4):661–673. 4. Howard SC, Gajjar AJ, Cheng C, et al. Risk factors for traumatic and bloody lumbar puncture in children with acute lymphoblastic leukemia. JAMA. 2002;288(16):2001–2007. 5. Fisher NC, Mutimer DJ. Central venous cannulation in patients with liver disease and coagulopathy–A prospective audit. Intensive Care Med. 1999;25(5):481–485. 6. Kam PC. Anaesthetic management of a patient with thrombocytopenia. Curr Opin Anaesthesiol. 2008;21(3):369–374. See Also (Topic, Algorithm, Electronic Media Element) • Platelets • Heparin-induced thrombocytopenia • Preeclampsia • von Willebrand’s disease

CODES

ICD9

• 287.30 Primary thrombocytopenia,unspecified • 287.49 Other secondary thrombocytopenia • 287.5 ICD10

• D69.49 Other primary thrombocytopenia • D69.59 Other secondary thrombocytopenia • D69.6 Thrombocytopenia, unspecified

CLINICAL PEARLS

• Bleeding time does not correlate with the risk of intraoperative bleeding. • Avoid platelet transfusion before the spleen is removed during splenectomy.

THYROIDECTOMY Joshua A. Atkins, MD, PhD

BASICS DESCRIPTION General

• Thyroidectomy describes the complete or partial excision of the thyroid gland. • Indications include – Hyperthyroidism due to autoimmune or multinodular thyroid disease – Thyroid malignancy – Thyroid nodules with growth potential – Goiter causing tracheal compromise, swallowing difficulty, or other discomfort • Exposure. Following a horizontal incision (lower neck, usually in skin crease if present) into the first three layers (skin, subcutaneous fat, and superficial fascia), the upper flap is elevated until it reaches the thyroid cartilage and the lower flap is pulled downward. The deep fascia is incised in a vertical, midline manner and the infrahyoid muscle is laterally retracted. • Identification of the parathyroid glands, recurrent laryngeal nerve (RLN), and superior laryngeal nerve (SLN) are performed to protect them from injury. • Devascularization to the thyroid gland involves clamping and ligating the – Superior thyroid artery; a branch of the external carotid. Ligation is typically made proximal to the gland to avoid injury to the external laryngeal nerve. – Inferior thyroid artery; a branch of the thyrocervical trunk. Ligation is performed distal to the superior and inferior parathyroid arteries to preserve the blood supply to the parathyroid glands. • The thyroid is dissected off the trachea (pretracheal fascia) to avoid damage prior to removal of the gland. • Endoscopic removal has been described but is not commonly performed.

Position

• Supine • Arms tucked to facilitate the surgeon’s access to the neck. • Shoulder rolled to hyperextend the neck and optimized exposure.

Incision

• Generally involves a small incision across the anterior neck at the level of the thyroid cartilage. • Dissection may be complicated in patients with aggressive cancer, prior surgery, or a history of radiation. • In rare cases, the thyroid gland extends into the mediastinum (retrosternal goiter) and a sternotomy incision is required.

Approximate Time 1–3 hours

EBL Expected Minimal

Hospital Stay

• Unilateral lobectomy is generally an outpatient procedure. • Total thyroidectomy is generally associated with a short inpatient admission.

Special Equipment for Surgery

• Intraoperative neuromonitoring may be performed in select cases (endotracheal tube with monitoring electrodes [e.g., NIM tube]). • Ultrasound for anatomic confirmation of lesion location (select cases).

EPIDEMIOLOGY Morbidity

• RLN damage. – RLN is a branch of the vagus nerve (CN X) and provides sensation to the trachea and innervation to all the muscles of the larynx (vocal cord adductors and the single abductor posterior cricoarytenoid), except the cricothyroid muscle. – Unilateral RLN damage leads to hoarseness. – Bilateral partial RLN damage (to the abductor) leads to stridor and respiratory distress (from unopposed adduction by the RLN and the SLN’s cricothyroid muscle). • SLN damage. – SLN is a branch of the vagus nerve and provides sensation to the larynx and innervation to the cricothyroid muscle. – Unilateral SLN damage has minimal effects. – Bilateral SLN damage leads to hoarseness and easy tiring of the voice. • Hypoparathyroidism. Inadvertent removal of the parathyroid glands can lead to acute hypocalcemia with spasticity/tetany. – If removal of parathyroid glands is recognized, they can be surgically reimplanted. • Hematoma leads to airway compromise. • Hypothyroidism (iatrogenic).

Mortality Rare

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Preoperative assessment of the indication for surgery, physiologic status, and size/location of mass. If the mass is extending into the mediastinum, a review of the CT scan and a discussion with the surgeon should be performed; the need for pulmonary function testing (flow-volume loops) or other imaging may be necessary to assess the extent of airway obstruction or potential for post-induction cardiovascular collapse due to impingement on central vascular structures.

• Hyperthyroidism should be aggressively treated prior to surgery unless emergency surgery is required. • Consult with the surgeon regarding the need for nerve monitoring. EMG monitoring necessitates avoidance of long-acting neuromuscular blockage. • Significant impingement on the trachea by thyrooid tissue can produce tracheomalacia with resultant dynamic collapse of the airway after removal (results in a variable, extrathoracic obstructive lesion).

PREOPERATIVE ASSESSMENT SYMPTOMS

• Compression of local structures – Dysphagia from esophageal compression – Dyspnea secondary to tracheal compromise – Hoarseness caused by compression of RLN or SLN • Hyperthyroidism. Palpitations, heat intolerance, weight loss, fatigue, hair loss, tremor, muscle weakness.

History

Patients typically present for surgery after a thyroid mass/nodule is found on incidental exam. The majority of patients are asymptomatic. Signs/Physical Exam

• Thyroid goiter • Tachypnea and/or stridor from airway compression • Hyperparathyroidism is associated with tachycardia, tremors, and perspiration • Exophthalmos/periorbital edema is associated with Grave’s disease. • Inability to lie flat on exam (air hunger). • Inability to produce a forceful cough during valsalva.

MEDICATIONS

• Beta-blockers (especially propranolol) treat the sympathetic response associated with elevated thyroid levels. • Propylthiouracil (PTU) or methimazole (MMZ) blocks the production of thyroid hormone.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Thyroid function tests: Thyroid stimulating hormone (TSH), T4 (free + total), T3 • CBC (mild anemia is common) • Electrolytes (including ionized calcium) • Flow-volume loops. Evaluate for airway obstruction in the sitting, reclining, and supine positions if anterior mediastinal mass is suspected or present. • ECG. Assess for normal rhythm, QT interval, and presence of other disease. • CXR. Evaluate for active infection, tracheal deviation, and extension into mediastinum.

• CT. Further assessment of mediastinal involvement and tracheal impingement. • Consider preoperative otorhinolaryngology consultation and functional vocal cord evaluation in patients with hoarseness or in high-risk procedures (cancer, reoperation, postradiation thyroid procedure). This is primarily a surgical issue to facilitate postoperative assessment of nerve injury.

CONCOMITANT ORGAN DYSFUNCTION

• Cardiac. Cardiomyopathy and/or atrial fibrillation if long-standing, untreated hyperthyroidism. • Neurologic. Grave’s disease is associated with ocular symptoms; neuropsychiatric symptoms can occur in severe hyperthyroidism.

TREATMENT PREOPERATIVE PREPARATION Premedications

Anxiolytics as appropriate; use with caution if airway compression is suspected. Special Concerns for Informed Consent None

INTRAOPERATIVE CARE Choice of Anesthesia

• General endotracheal anesthesia is the most common approach. – LMAs can be considered in select patients. • Local/regional block with sedation can be considered in select patients (not common). – Cervical plexus block with local infiltration. – Not optimal for monitoring cases or procedures involving large goiters and invasive disease. Monitors

• Standard ASA monitors. • Neuromonitoring (select cases). • Invasive arterial monitoring in patients with significant risk of thyrotoxicosis.

Induction/Airway Management

• In most patients, the thyroid goiter has minimal impingement on the airway and no special measures are required. • Patients with a significant tracheal impingement should undergo topicalized, awake fiberoptic intubation. – Tracheal compromise is suggested by CT findings, an obstructive pattern on flow-volume loops, or the presence of severe dysphagia, hoarseness/stridor, or difficulty lying flat. – Consider using a small ETT if tracheal compression is suspected. • Videolaryngoscopy (GlideScope, etc.) can facilitate placement of the EMG’s electrode sensors

at the vocal cords. – Allows the surgeon and neurophysiologist to confirm placement of the tube and avoid repeated laryngoscopy. – Used intraoperatively to reevaluate the position of electrodes if the signal is lost.

Maintenance

• General anesthesia with volatile anesthetics or total IV anesthetic. • Muscle relaxant is not necessary for surgical exposure. Avoid long-acting relaxant if monitoring the RLN. • Consider dexamethasone for postoperative nausea and vomiting prophylaxis and modulation of airway edema.

Extubation/Emergence

• Carefully consider the need for postoperative intubation. Tracheomalacia, leading to dynamic airway obstruction, can occur in patients with significant preoperative tracheal involvement by the thyroid mass. Acute airway obstruction is a concern in the setting of intraoperative RLN injury. – Functional evaluation of vocal cord function can be performed at emergence via fiberoptic assessment. Performed as the ETT is withdrawn at emergence or via an LMA placed prior to emergence. – Continuous real-time monitoring for vocal cord movement during surgery with fiberoptic bronchoscopy through an LMA has been proposed. – Low-dose remifentanil infusion (0.02–0.05 μg/kg/min) may facilitate tolerance of the ETT and functional vocal assessment, while minimizing coughing. • Avoid coughing at emergence. Straining against the ETT may promote suture disruption and hematoma formation. Postoperative hematoma formation can cause airway compromise. – Resumption of spontaneous ventilation during closure may facilitate prompt extubation on emergence. – Suctioning of the airway should be done before extubation and while the patient is “deep” to remove any accumulated blood or secretions that can stimulate coughing.

FOLLOW-UP BED ACUITY

• Routine nursing care • In complicated procedures, there is significant concern for RLN injury and respiratory symptoms; consider prolonged PACU stay and monitored floor bed.

ANALGESIA

• Acetaminophen • Opioid • Local infiltration • Cough lozenges

COMPLICATIONS

• Hypoparathyroidism with acute hypocalcemia and tetany • Recurrent laryngeal nerve injury with hoarseness or obstruction • Tracheomalacia with dynamic airway obstruction • Neck hematoma from post-surgical bleeding that may occur suddenly after an episode of wretching or coughing – This is a surgical emergency. Airway management can be exceptionally challenging due to compression from the hematoma. – The most effective intervention is surgical decompression of the neck hematoma at the bedside prior to induction of anesthesia or attempted intubation.

REFERENCES

1. Dillon FX.Electromyographic (EMG) neuromonitoring in otolaryngology-head and neck surgery. Anesthesiol Clin. 2010;28(3):423–442. 2. Murkin JM.Anesthesia and hypothyroidism: A review of thyroxine physiology, pharmacology, and anesthetic implications. Anesth Analg. 1982;61(4):371–383. 3. Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin N. 2006;35:663–686. 4. Yerzingatsian KL. Thyroidectomy under local analgesia: The anatomical basis of cervical blocks. Ann Roy Coll Surg Eng. 1989;71:207–210. See Also (Topic, Algorithm, Electronic Media Element) • Electromyelography (EMG) • Recurrent laryngeal nerve • Superior laryngeal nerve • Anterior mediastinal mass • Flow volume loops • Hyperthyroidism

CODES ICD9 • 193 Malignant neoplasm of thyroid gland • 242.90 Thyrotoxicosis without mention of goiter or other cause, and without mention of thyrotoxic crisis or storm ICD10 • C73 Malignant neoplasm of thyroid gland • E05.90 Thyrotoxicosis, unsp without thyrotoxic crisis or storm

CLINICAL PEARLS

• Enlargement of the thyroid gland can cause compression of the trachea, esophagus, and RLN.

• Patient should be euthyroid before proceeding with an elective thyroidectomy. • Thyroid storm is a medical emergency that may present in a patient with hyperthyroidism. – Common manifestations include arrhythmias (SVT and Afib) and hyperthermia. – Acute treatment includes beta-blockade, corticosteroids, PTU, and antipyretics. • Neuromonitoring is generally reserved for more invasive thyroid masses. • Smooth emergence minimizes the risk of hematoma formation and airway compromise.

TIDAL VOLUME Quinn L. Johnson, MD

BASICS DESCRIPTION

• The principal function of respiration is to exchange oxygen and carbon dioxide with circulating blood at the level of the alveoli (takes place during inspiration and expiration). • Tidal volume (TV) refers to the amount of air that is involved in one half of respiration, either the volume of expiration or the volume of inspiration. In addition to being used to calculate minute ventilation (respiratory rate times TV), it serves as a major component of several lung capacities: – Total lung capacity (TLC) – Inspiratory capacity (IC) – Forced vital capacity (FVC) • The concept of the TV is utilized when discussing: – Spontaneous ventilation: An average measure of inspiration or expiration volumes that occurs for an individual, typically during normal breathing. Direct measurement of the TV occurs using a spirometer or through a variety of lesser-utilized dilutional techniques. – Mechanical ventilation: The amount of air delivered or returned into the breathing circuit. Volume modes allow for the TV to be set; they are often pressure limited to avoid barotrauma. Conversely, pressure modes have variable tidal volumes and depend on the lung’s compliance. PHYSIOLOGY PRINCIPLES

• Normal values – Spontaneous ventilation: ∼6–7 cc/kg; for an average 70 kg adult, this equates to roughly 500 cc of volume. – Mechanical ventilation: ∼7–15 cc/kg are programmed for delivery secondary to compliance of the circuit, chest wall resistance, and increased apparatus dead space. • Components of TV. Not all of the TV is involved in air exchange. Dead space describes the portion of the volume not involved in actual gas exchange. – Anatomic dead space: Involves passageways such as the trachea and upper bronchioles. Typically around 30%. – Alveolar dead space: Alveoli that are not being perfused (contributes a negligible amount in healthy patients). – Physiologic dead space: The combined volume of the anatomic and pathologic dead space. This is roughly equivalent to 2 cc/kg or 150 cc in an adult. – Apparatus, mechanical, or equipment dead space describes the additional TV that does not participate in air exchange (endotracheal tube, laryngeal mask airway, corrugated extendors, humidifiers, etc.). Clinically, this is often minor in adults, but can become significant in pediatrics, particularly neonates.

• Movement of air – Spontaneous ventilation at rest. Inspiration, at rest, results primarily from contraction of the diaphragm and the external intercostal muscles. This causes an increase in the thoracic cavity volume and the development of negative pressure compared to the atmosphere. The pressure difference that is created allows the flow of air into the pulmonary system. Expiration, at rest, is normally passive. As the muscles of inspiration relax, the thoracic cavity decreases in volume and the elastic recoil of the lungs act in concert to create a positive pressure compared with the atmosphere; air flows out of the pulmonary system. Not all of the air is expelled from the lungs; the volume left behind is referred to as the functional residual capacity (comprises the expiratory reserve volume and residual volume). – Spontaneous ventilation during disease states or distress. Adequate oxygenation requires the use of accessory muscles. Inspiration can involve the scalene, sternocleidomastoid, or pectoralis muscles. Expiration becomes an active process and involves the abdominal muscles or internal intercostals. – Mechanical ventilation. Inspiration is dependent on the generation of positive pressure. Two general modes for controlled ventilation are commonly used: Volume control and pressure control. Volume control will attempt to deliver a preset volume of gas to the patient using a variable, but limited, amount of pressure. Pressure-dependant ventilation utilizes a set pressure and, therefore, results in variable TVs to the patient. Volumes and pressures then can be adjusted based on clinical and laboratory values to optimize ventilation. Expiration remains a passive process; occurs after the removal of positive pressure ventilation due to chest wall recoil and peritoneal cavity contents. • Measurements of TV – Spirometry: A device that measures the volume of air for both inspiration and expiration breathed by a patient. The rate of volume movement is also recorded. Overall, it provides a means to identify possible pulmonary pathology (e.g., COPD, pulmonary fibrosis). – Ventilator. TV can be measured directly using a respirometer, usually found in the expiratory limb of the ventilator circuit. A unidirectional microvane or a bidirectional volumeter is physically spun by the gas flow as it leaves the patient; the number of rotations correlate (are calibrated) to a specified TV. A second indirect measure of TV is a gas flow rate meter found in newer equipment. Ultrasound techniques measure the volume of air moving past the transducers and the TV is calculated based on this relationship. • Position – Spontaneous ventilation. In the supine position, the relaxed diaphragm is located higher in the thoracic cavity compared to when the patient is in a standing or upright position. Because of this height difference, the diaphragm will have more space to contract and results in a larger volume being moved for a given amount of energy (work). – Mechanical ventilation. Often performed in the supine position. Neuromuscular blockade and/or general anesthesia result in the diaphragm rising high into the thoracic cavity from abdominal contents pushing against a “weakened" diaphragm. This will result in decreased lung volumes, and therefore, larger pressures are necessary to expand the alveoli when ventilating a patient.

– Prone and, to a lesser degree, lateral positioning can improve respiratory mechanics secondary to the effects of gravity (shifting of abdominal contents and improved diaphragm excursion). Similarly, a patient in reverse Trendelenburg has improved respiratory mechanics compared to the supine and Trendelenburg position.

DISEASE/PATHOPHYSIOLOGY

• Impaired oxygenation or ventilation in the spontaneously ventilating patient often results in the recruitment of accessory muscles during inspiration and expiration to increase the TV and compensate for increases in dead space or shunting. However, not all pathological processes are limited to the pulmonary system, and may include cardiac and metabolic disease. • Dead space increases in either mechanical ventilation or spontaneous breathing in the following situations: – Rapid, shallow breathing as may be seen from abdominal or thoracic incisional pain. The smaller TVs result in an increased fraction of dead space (can exceed 50%). – Pulmonary embolism prevents perfusion to alveolar units being ventilated, thus increasing pathological dead space. The location of the embolism will determine the extent of the increase in dead space. – Cardiac arrest/severe hypotension results in alveolar units that continue to be ventilated but now have decreased or absent perfusion. • Obesity. Pulmonary compliance may decrease by 35% in morbidly obese patients secondary to reductions in both pulmonary and chest wall compliance. This results in an increased respiratory rate, but smaller TVs. This breathing pattern creates a preferential ventilation of poorly perfused lung tissue and leads to hypoxemia and/or hypercapnia particularly while under anesthesia (1) unless TVs are augmented. • Geriatrics. Lung volumes decrease; however, the volume solely attributable to age is difficult to predict because smoking history, occupational illnesses, environmental conditions, and exposure to lung pollutants also factor into the decrease. The loss of height associated with spinal osteoporosis can affect thoracic volumes (2). In addition, the internal structure of the lungs is affected; TV begins to decrease in the mid-40’s secondary to an increasing closing volume. The encroachment of closing volume on TV increases with age such that by age 65 they are equal in the sitting position. In general, respiratory rates remain unchanged and there is a diminished response to correct hypercapnia or hypoxia.

Pregnancy Considerations

• Changes begin early as the uterus increases in size; they become more clinically obvious and peak during the 3rd trimester. The gravid uterus will displace the diaphragm superiorly, by up to 4 cm, and the thoracic cavity will increase both the transverse and anteroposterior diameters in part due to the effects of the hormone relaxin. As a result, respiration becomes more dependent on the diaphragm (3). While several lung volumes are decreased during pregnancy (expiratory reserve volume, residual volume, and functional residual volume), the TV component increases by up to 40%. Oxygen consumption and carbon dioxide production will increase in large part due to the growing fetus, but this is matched with an increase in minute ventilation by 30–50%. The increase in minute ventilation is attributable to progesterone, known to stimulate increased ventilation directly at the respiratory center

found in the medulla. The increase in minute ventilation will cause the arterial partial pressure of CO2 to decrease to between 26 and 32 mm Hg. Pediatric Considerations

• Both dead space and TV estimations per kilogram remain constant in the pediatric population. However, accurate estimation and then delivery of that TV becomes more difficult for mechanical ventilation. Because the volume being delivered is very small, even minor issues can have an unexpectedly large impact on the actual volume that is delivered. Volume can be lost secondary to the compliance of the breathing circuit, or a leak in the ventilator circuit due to the number of accessory items (humidifiers or heaters). To that extent, specialized pediatric circuits can be utilized (less compliant, smaller ventilation bags) and pediatric ventilators can improve TV delivery. Despite these improvements, vigilance is necessary to avoid inadequate ventilation leading to hypoxia and hypercapnia (4).

PERIOPERATIVE RELEVANCE

• Obesity. Initial interventions include increasing TV and/or adding PEEP. However, the dangers of a greatly increased TV include hyperventilation, hypocapnia, high airway pressures, and increased risk of parenchyma damage due to the combination of volume and pressure. Frequently, while normalizing oxygen levels, hypocapnia results. The respiratory alkalosis can cause a shift in the oxyhemoglobin curve that increases affinity of the heme molecule for oxygen and results in worsening of tissue oxygenation (5). The strategy for maintaining oxygenation and normocapnia for obese patients is complex, particularly during laparoscopic surgery. Despite multiple studies, no single method has been demonstrated to improve ventilation. • Acute lung injury. Recent studies have indicated that patients who have acute lung injury such as ARDS may benefit from low TVs (6 cc/kg) when utilizing mechanical ventilation. These lower volumes have been associated with lower serum concentrations of inflammatory mediators. Overall, this is correlated with a decrease in mortality in patients who have ARDS and other acute lung injury (6). • The geriatric patient is at increased risk of hypoxia, particularly when sedated and the use of supplementary oxygen is warranted even for simple procedures (7).

EQUATIONS

• IC = TV + IRV, where IC is inspiratory capacity, TV is tidal volume, and IRV is inspiratory reserve volume. • FVC = IRV + TV + ERV, where FVC is forced vital capacity and ERV is expiratory reserve volume. • TLC = IRV + TV + ERV + RV, where TLC is total lung capacity and RV is residual volume.

REFERENCES

1. Sprung J, Whalley DG, Falcone T, et al. The effects of tidal volume and respiratory rate on oxygenation and respiratory mechanics during laparoscopy in morbidly obese patients.

Anesth Analg. 2003;97:1. 2. eleznik J. Normative aging of the respiratory system. Clin Geriatr Med. 2003;19:1.

3. obrowski RA. Pulmonary physiology in pregnancy. Clin Obstet Gynecol. 2010;53:285–300.

4. amel RRT, Cheifetz MD. Measuring pediatric tidal volumes. RT: For Decision Makers in Respiratory Care. 2002. 5. ardoczky GI, Yernault JC, Houben JJ, et al. Large tidal volume ventilation does not improve oxygenation in morbidly obese patients during anesthesia. Anesth Analg. 1995;81:385–388.

6. Parsons PE, Eisner MD, Thompson BT, et al. Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med. 2005;33(1):1–6. 7. Bailey PL, Wilbrink J, Zwanikken P, et al. Anesthetic induction with fentanyl. Anesth Analg. 1985;64:48–53. 8. Bachiller PR, McDonough JM, Feldman JM. Do new anesthesia ventilators deliver small tidal volumes accurately during volume-controlled ventilation? Pediatric Anesthesiology. 2008;106(5):1393–1400. See Also (Topic, Algorithm, Electronic Media Element) • Functional residual capacity • Dead space ventilation

CLINICAL PEARLS

• Newer ventilators have been “tweeked" to compensate for the compliance of the breathing system and adjust for changes in fresh gas flow; this allows for the programmed volume to more appropriately match the delivered volume. In pediatric patients, this can facilitate volume control ventilation and improve matching of desired TV with that of delivered TV.

TONSILLECTOMY AND ADENOIDECTOMY Joshua A. Atkins, MD, PhD

BASICS DESCRIPTION General

• Tonsillectomy and adenoidectomy (T&A) is one of the most common surgical procedures undertaken each year, although frequency has steadily declined. The procedure involves surgical excision of lymphatic tissue that is either – The source of recurrent infections (tonsil/adenoid/inner ear) with associated pain, inflammation, or abscess – Neoplastic (usually associated with additional procedures such as neck dissection) – Hyperplastic and contributing to airway obstruction during sleep as part of the obstructive sleep apnea (OSA) syndrome • The operative site, the oropharynx, is visualized with the aid of a mouth gag; a device utilized to prop open the mouth and keep the endotracheal tube (ETT) away from the surgical field. It can be suspended onto the Mayo stand. • Local anesthetic with epinephrine is usually injected to provide pain relief and surgical hemostasis (vasoconstriction). A throat pack is also inserted to prevent aspiration of blood • Adenoidectomies, when performed, are done first, as they are more posterior. The tonsillar capsule is then dissected away from the surrounding muscle. A variety of devices can be used including standard cautery, laser, Harmonic Scalpel, and Coblation. In select patients, it may be performed robotically. Position

• Supine, bed rotated 90° away • Shoulder roll to facilitate visualization; head rest

Incision Small

Approximate Time 20 minutes

EBL Expected Minimal

Hospital Stay

• Ambulatory typically • Overnight depending on comorbidities (e.g., OSA)

Special Equipment for Surgery

• Laser or robot in some institutions • Mouth gag

EPIDEMIOLOGY Prevalence

Majority of procedures performed in pediatric patients (75%). Morbidity

• Sore throat (up to several weeks) • Bleeding requiring emergent reexploration (not uncommon) • Airway swelling (rare)

Mortality

Rare: 1:40,000 procedures

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Common procedure in pediatric patients; may be the first exposure to a general anesthesia (GA) and risk factors such as malignant hyperthermia must be considered. Succinylcholine, although suitable for the procedure, should be avoided in this population. • Procedure requires deep anesthesia and immobility. The short duration of the procedure precludes the routine use of non-depolarizing muscle relaxants in many cases. “Deep extubation” to avoid laryngospasm, as well as coughing and bucking (increases suture stress) against obstruction, bleeding, and aspiration. • Patients with OSA may be difficult to ventilate after induction, more likely to obstruct after extubation, and sensitive to sedatives and opioids. Depending on severity, may need noninvasive respiratory support postoperatively or overnight admission.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Recurrent sore throat, pharyngitis, otitis media • Dysphagia • Mouth breathing, daytime somnolence, nighttime awakening, snoring (suggestive of OSA)

History

• Screen for active, severe infection; recognize that in patients with recurrent tonsillitis, complete resolution of infection is unlikely to occur without removal of the glands. • Screen for OSA; determine if using a continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) machine at home and the settings. • In patients with cancer, review CT scan, notes from the ENT surgeon, prior biopsies, etc.

Signs/Physical Exam

• Airway exam • Large neck circumference • Enlarged tonsils

• Pulmonary exam for signs of significant active infection, wheezing, chronic hypoxia • Dental assessment for loose or chipped teeth

MEDICATIONS

• Antibiotics; may have an increased incidence of antibiotic allergies due to repeated therapy. • Asthma medication; chronic obstruction by hypertrophic tonsils may be initially misdiagnosed as reactive airway disease. • Use of aspirin should be discontinued for 7 days and other NSAIDS for 3 days prior to operation. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• PT/PTT, INR (usually part of standard workup to identify any unsuspected bleeding diathesis) • CBC • ECG in OSA patients; assess for increased P-wave amplitude or right axis deviation that suggest right ventricular hypertrophy • Review sleep study in OSA patients for Apnea Hypopnea Index (AHI) as a measure of OSA severity. An AHI >30 indicates severe disease; an AHA <15 indicates mild disease. CONCOMITANT ORGAN DYSFUNCTION

• If associated with obstructive sleep apnea, patient may demonstrate pulmonary hypertension and cardiac dysfunction from chronic hypoxemia. • May demonstrate metabolic syndrome associated with morbid obesity (glucose intolerance, hypertension, hyperlipidemia).

TREATMENT PREOPERATIVE PREPARATION Premedications

• Sedatives and opioids are generally avoided in OSA patients. • Consider midazolam in pediatric patients without OSA. • Antisialogogues may be considered to reduce secretions.

Special Concerns for Informed Consent

• Consent of parents in pediatric cases. Parents may accompany the child into the OR for mask induction as deemed appropriate. • For OSA patients, request that the patient bring their own CPAP/BiPAP (compatibility with different devices can vary significantly).

Antibiotics/Common Organisms Third-generation cephalosporin INTRAOPERATIVE CARE

Choice of Anesthesia

GA with either • ETT; standard approach • Flexible laryngeal mask airways (LMAs) may be considered in special circumstances • Natural airway under GA in select healthy pediatrics patients for fast procedures

Monitors

Standard ASA monitors

Induction/Airway Management

• Induction is typically via IV or inhalational induction, followed by ETT placement. – Oral R.A.E. tubes are typically utilized; they have a fixed curvature such that the size of the tube must be appropriately matched to the size of the patient (e.g., distance from the pharynx to the glottis). Secure the R.A.E. tube to the center of the lower jaw, not off to one side. – Standard ETTs are preferred in unilateral tonsillectomies (e.g., cancer), and are secured to the opposite side. – Laser tube should be considered if CO2 laser will be used for resection.

– Topical lidocaine (4% LTA) during laryngoscopy can reduce laryngeal responsiveness during surgery. – Muscle relaxation can optimize intubating conditions but procedures tend to be very short with nondepolarizing relaxant invariably outlasting the duration of the procedure. – Succinylcholine is an alternative possibility but is associated with a risk of malignant hyperthermia (pediatrics, first GA) and significant myalgia in outpatients. – In cancer, take special care to avoid traumatic laryngoscopy that may disrupt the lesion causing significant bleeding and the potential for airway compromise. – Consider videolaryngoscopy in cancer and OSA patients. – In morbidly obese patients, consider the ramp position and denitrogenation with CPAP/pressure support. • LMA (flexible version) can be considered in special circumstances. – Allows airway management at a lighter plane of anesthesia without incumbent risks of intubation. – Avoids the need for muscle relaxants – May be less stimulating in the pediatric patient with active pharyngeal inflammation – May exhibit less emergence phenomenon – Requires familiarity with flexible LMA – Requires collaboration with surgeon – Vigilance for possibility of kinking of LMA by mouth gag – Must be prepared for rapid conversion to ETT.

Maintenance

• Volatile or IV maintenance is typically utilized to provide deep levels of anesthesia. • IV maintenance with propofol and remifentanil infusion may facilitate – Airway management and intraoperative immobility without muscle relaxant

– Rapid emergence with a more smooth transition to consciousness – Decreased risk of nausea and vomiting • Caution as the surgeon places a mouth gag (deep levels of anesthesia and potential for displacement or compression of the ETT) • Analgesia. Rectal acetaminophen may be administered in pediatric patients. Ketorolac is generally avoided as it can potentiate bleeding via platelet inhibition; even mild bleeding in the airway can be dangerous. Minimal intraoperative opioid is suggested, as it can be titrated more aggressively after extubation. Fentanyl 2–3 μg/kg is adequate for many patients. • Consider dexamethasone for dual-agent postoperative nausea and vomiting prophylaxis, modulation of edema formation, and reduced inflammatory pain component.

Extubation/Emergence

• Use gentle suctioning during emergence to avoid disruption of surgical hemostasis. More than a trace of blood in post-extubation secretions should be evaluated by the surgeon prior to leaving the operating room. • Goal is to minimize coughing and bucking that can move the tube against the surgical incision and increase the risk for suture disruption and rebleeding. • Suctioning of the airway should be done before extubation to remove any accumulated blood. • Prophylactic antiemetic to reduce risk of suture disruption from retching • Deep extubation. May minimize the stimulation of the ETT during emergence; this must be balanced with the risks of blood in the airway, soft-tissue obstruction, and laryngospasm. • OSA patients. Consider extubation in the head-up position and immediate transition to CPAP/BiPAP until ready for PACU discharge. In the OR, this can be accomplished with a Mapleson circuit, bag/valve/mask system, or even more readily with the Boussignac CPAP system. In severe OSA and a difficult airway, consider short-term postoperative intubation to allow for decompression of peritonsillar edema.

FOLLOW-UP BED ACUITY

• In OSA patients, continuous pulse oximetry monitoring and possibly overnight stay. • Nursing familiarity with noninvasive ventilation modes.

ANALGESIA

• Acetaminophen • Opioids (oral, IM, IV) • Cool liquids

COMPLICATIONS

• Bleeding is the most common complication (up to 5%) and requires emergent surgical intervention. – Bleeding occurs at two times: Within hours of the initial surgery or after 1 week when the

scab is displaced from the surgical site. – Necessitates emergent reoperation – There may be significant clot or active bleeding in the airway. – Difficult to quantify blood loss; consider preinduction volume resuscitation and hemoglobin measurement in pediatric patients. – Airway management is subsequently challenging; videolaryngoscopy may not be helpful in a bloody airway. – Consider rapid sequence induction versus risks of aspiration and obstruction with inhalational induction and maintenance of spontaneous ventilation. – In pediatric patients bleeding may be associated with significant hypovolemia that should be corrected prior to induction – Prior to extubation, evacuation of gastric contents should be considered as heme is a potent trigger for PONV; placement of an orogastric tube under direct vision is preferable to blind placement in such patients • Postextubation laryngospasm (especially pediatrics) with associated hypoxemia – Treat with jaw thrust, positive pressure ventilation, or timely administration of muscle relaxant with hypnotic agent, if an oral airway is inserted, use caution to avoid damage to sutures and surgical site. – May be prevented with good suctioning, surgical hemostasis, deep extubation – Monitor for signs and symptoms of pulmonary edema (hypoxia, frothy secretions, dyspnea), and consider CXR and hospital admission if present.

REFERENCES

1. Batra YK, Al Qattan AR, Ali SS, et al. Assessment of tracheal intubating conditions in children using remifentanil and propofol without muscle relaxant. Paediatr Anaesth. 2004;14(6):452–456. 2. Fields RG, Gencorelli FJ, Litman RS. Anesthetic management of the pediatric bleeding tonsil. Paediatr Aneasth. 2010;20(11):982–986. 3. Gravningsbraten R, Nicklasson B, Raeder J. Safety of laryngeal mask airway and short-stay practice in office-based adenotonsillectomy. Acta Anaesthesiol Scand. 2009;53(2):218–222. 4. Mandel JE. Laryngeal mask airways in ear, nose, and throat procedures. Anesthesiol Clin. 2010;28(3):469–483. 5. Paul W. Flint Ed. Cummings: Otolaryngology Head and Neck Surgery, 5th edn. Philadelphia: Elsevier, 2010. See Also (Topic, Algorithm, Electronic Media Element) • Post-tonsillar bleed • Obstructive sleep apnea • Deep extubation • Laryngospasm

CODES

ICD9

• 463 Acute tonsillitis • 474.00 Chronic tonsillitis • 474.01 Chronic adenoiditis ICD10

• J03.90 Acute tonsillitis, unspecified • J03.91 Acute recurrent tonsillitis, unspecified • J35.01 Chronic tonsillitis

CLINICAL PEARLS

• Common indications are recurrent infection and OSA. OSA patients have an increased risk of obstruction after induction and extubation, as well as sensitivity to opioids and sedatives.

TOTAL LUNG CAPACITY Arne O. Budde, MD, DEAA

BASICS DESCRIPTION

• Total lung capacity (TLC) is the volume of the lungs at the end of a maximal inspiration. It is measured in liters (or milliliters) and is approximately 4–6 L in a normal adult. • It is dependent on several factors including age, height, gender, sex, ethnicity, and sometimes weight or body surface area. • TLC helps differentiate between restrictive and obstructive lung disease. In the perioperative period, anaesthetist are frequently concerned about the functional residual capacity (FRC), a component of the TLC. PHYSIOLOGY PRINCIPLES

• Lung volumes are direct measurements of the various respiratory parameters in the respiratory cycle. Commonly measured volumes include – Residual volume (RV): The volume of gas that persists in the lungs after a maximum expiratory effort. – Expiratory reserve volume (ERV): The volume of additional gas that can be exhaled at end-expiration of a tidal volume breath (or FRC). – Tidal volume (TV): The volume of gas that an individual is normally breathing in and out. – Inspiratory reserve volume (IRV): The maximum volume of gas that can be inspired at the end-inspiration of a tidal volume breath. • Lung capacities comprise two or more of the above-listed lung volumes to describe the different phases of the respiratory cycle. Commonly calculated capacities include – FRC: The volume of gas at the position of a normal end-tidal expiration. – Vital capacity (VC): The maximal volume of gas that can be expired from the lungs from the position of maximal inspiration; or alternatively, the maximal volume of gas that can be inspired from the position of maximal expiration (residual volume). – TLC: The volume of the lungs at maximal inspiration. • TLC comprises the sum of all the lung volumes: TLC = RV + ERV + TV + IRV. TLC is the total lung volume or capacity, as its name implies. • Simple spirometry alone cannot measure the TLC. Spirometry measures air movement into or out of a mouthpiece; and it is impossible to exhale the RV. • The FRC can be measured using one of three commonly utilized techniques, with subsequent calculation of the RV and TLC (1). Techniques include the helium dilution (wash-in) technique, nitrogen wash-out technique, and whole body plethysmography. • Factors affecting lung volumes and hence TLC include height, gender, and ethnic origin. – White adult male: 6.5 L – White adult female: 5.5 L – Asian and Afro-Caribbean populations have 10–15% lower volumes than Caucasians (2).

• Normal ratios – FEV1/FVC: The majority of a forced vital capacity (FVC) is exhaled within the first second.

– RV/TLC: Small and demonstrates that the majority of the TLC is available for volume exchange; conversely, the majority of the TLC is the VC. TLC – VC = RV.

ANATOMY

• The American Thoracic Society and the European Respiratory Society (ATS/ERS) have published guidelines including regression equations for reference values for lung volumes and capacities (3,4). Average normal adult values for lung volumes and capacities are defined as follows – RV: 1,200 mL – ERV: 1,200 mL – TV: 500 mL – IRV: 300 mL – VC : 4,500 mL – FRC: 2,400 mL – TLC: 6,000 mL

DISEASE/PATHOPHYSIOLOGY

• The values of TLC, VC, FRC, and FEV1 enable the physician to differentiate between

restrictive and obstructive lung disease (5). • Obstructive airway disease – Includes asthma, chronic obstructive lung disease (chronic bronchitis and emphysema), bronchiectasis, cystic fibrosis, and bronchiolitis. – FEV1/FVC ratio decreases

– TLC is normal or increased. Increased TLC results from hyperinflation as seen with emphysema; due to a loss of parenchymal elastic recoil. – The RV/TLC ratio often exceeds 60% in COPD; in other words, the RV increases from air trapping with forced exhalation and is not available for volume movement/exchange. • Restrictive lung disease – Includes lung parenchymal diseases such as sarcoidosis, idiopathic pulmonary fibrosis, and interstitial lung disease from either medications or radiation. – Extraparenchymal diseases include neuromuscular pathologies (diaphragmatic weakness and paralysis, myasthenia gravis, Guillain–Barré syndrome, muscular dystrophies, and cervical spine injury) and chest wall pathologies (kyphoscoliosis, obesity, and ankylosing spondylitis). – FEV1/FVC is normal or increased. – TLC is decreased. The American Thoracic Society’s criteria for grading the severity of restrictive lung function states that Mild disease: TLC ≥70% of normal Moderate disease: ≥60–70% Moderately severe: TLC <60%. – The RV/TLC ratio is preserved in fibrosis (RV decreases to a similar extent). In extrapyramidal disease that is characterized by inspiratory dysfunction, RV is not

significantly affected (RV/TLC may be increased).

PERIOPERATIVE RELEVANCE

• During preoxygenation the TLC is filled with 100% oxygen to provide a cushion during apnea or in the event of “cannot ventilate, cannot intubate.” Although the FRC cannot be measured easily in the perioperative period, its storage capacity is nevertheless utilized. • Anesthesia and postoperative medications alter lung volumes and ventilatory pattern – TLC decreases postoperatively: Thoracic and upper abdominal surgery >lower abdominal surgery >peripheral surgery. – VC is decreased by 25–50% after surgery and normalizes after 1–2 weeks. – Supine positioning decreases FRC by 10–15%. – Tracheal intubation slightly decreases FRC. – General anesthesia further reduces FRC by 5–10%. • Effect of altered lung volumes on anesthesia – The RV/TLC ratio correlates with outcome following thoracic surgery: A RV/TLC ratio of >50% is indicative of a high-risk patient for pulmonary resection. – Rapid desaturation during apnea occurs within seconds even after preoxygenation with an FiO2 of 1.0.

– High peak airway pressures due to stiff lungs lead to increased risk of barotrauma and volutrauma. • Effect of age on lung volumes – Young adults have a RV/TLC ratio of 25%; therefore, 75% of the TLC can be expired. – Elderly patients have an increasing RV/TLC ratio (up to 45% in a 75-year old) due to decreased lung and airway elasticity. Airways tend to close prematurely with resultant decreases in VC and increases in RV.

EQUATIONS

• TLC = RV + ERV + TV + IRV; where TLC is the total lung capacity, RV is residual volume, ERV is expiratory reserve volume, TV is tidal volume, and IRV is inspiratory reserve volume • TLC = RV + VC; where VC is the vital capacity

GRAPHS/FIGURES

FIGURE 1. Respiratory volumes and capacities.

REFERENCES

1. Clayton N. Lung function made easy: Assessing lung size. Chron Respir Dis. 2007;4(3):151– 157. 2. ankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999;159:179–187. 3. American Thoracic Society. Lung function testing: Selection of reference values and interpretative strategies. Am Rev Respir Dis. 1991;144(5):1202–1218. 4. Wanger J, Clausen JL, Coates A, et al. Standardisation of the measurement of lung volumes. Eur Respir J. 2005;26(3):511–522. 5. Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J. 2005;26(5):948–968.

ADDITIONAL READING

• AARC Clinical Practice Guideline. Static lung volumes. 2001 revision and Update. Respir Care. 2001;46(5):531–539. • http://www.thoracic.org/education/pulmonary-function-testing/index.php See Also (Topic, Algorithm, Electronic Media Element) • Functional residual capacity • Tidal volume • Spirometry • Residual volume

CLINICAL PEARLS

• TLC has perioperative relevance to the anaesthetist during preoxygenation prior to

induction. Although the RV is not available for volume exchange, it is capable of being utilized as an oxygen store. • Preoperative evaluation of lung disease may involve measuring the FEV1, FEV, and VC and can assist with diagnosis, stratification, progression, or response to therapy. • TLC cannot be measured by simple spirometry.

TOTAL SPINAL Sharon L. Lin, MD Jane C. Ahn, MD

BASICS DESCRIPTION

• A total spinal can result from inadvertent introduction of local anesthetics into the intracranial subarachnoid space. Typically results from unintentional dural puncture, subdural spread, or catheter migration with epidural placement. • Early signs and symptoms may include anxiety, numbness/weakness of the arms and hands, and dyspnea. As the local anesthetic reaches the brainstem, apnea, hypotension, bradycardia, and loss of consciousness may occur rapidly • Spread of local anesthetic within the intrathecal space is affected by: – Dose – Patient position relative to baricity – Patient characteristics – Spinal/epidural technique • The potential for a total spinal as well as systemic local anesthetic toxicity make it mandatory that equipment to ventilate, intubate, and resuscitate should be immediately available whenever a neuraxial or regional block is performed. EPIDEMIOLOGY Prevalence

• Overall incidence of total spinal anesthesia after epidural placement is <0.03%. • Overall incidence of total spinal anesthesia after a spinal anesthetic is 0.2%.

Morbidity

If treated promptly, morbidity and mortality is minimal. Mortality

• Typically results from delayed recognition and treatment of apnea and cardiovascular collapse. Unrecognized apnea has a 100% mortality. ETIOLOGY/RISK FACTORS

• Unintentional dural puncture • Epidural catheter migration • Surbarachnoid catheter placement • Subdural spread of local anesthetic causing high block • Combined spinal epidural (CSE) • Large volume injection into the epidural space (compresses spinal canal, promoting cephalad spread of intrathecal drugs)

• Injection of local anesthetic at a high thoracic level • High doses of local anesthetic in spinal block • Retrobulbar block • Peripheral nerve blocks – Interscalene block – Lumbar plexus block – Intercostal nerve block (injection via dural cuff extending along nerve root) – Blocks performed under general anesthesia • Pregnancy • Chronic pain procedures – Cervical spine injection

PHYSIOLOGY/PATHOPHYSIOLOGY

• Local anesthetics block fast sodium channels and neurotransmission when in contact with the spinal cord. Perioperative analgesia and anesthesia can be achieved through blockade of sensory and motor conduction at specific dermatomes targeted to the level of surgical incision. • However, if cephalad spread of local anesthetic within the intrathecal space occurs, undesired effects, including a total spinal may result. A total spinal is when local anesthetic medications are introduced into the intracranial subarachnoid space, resulting in the sudden onset of apnea, bradycardia, hypotension, and unconsciousness. • Pathophysiology and clinical manifestations depend on the spinal level that the local anesthetic reaches, and may range from a high spinal to a total spinal. – Thoracic. Respiratory difficulty results from the loss of chest wall sensation by paralysis of the intercostal muscles. Patients with a high spinal often describe their breathing as feeling abnormal; however, can demonstrate a good inspiration and can cough and speak normally. – Cervical. As the block rises higher, the diaphragmatic nerves (C3, 4, 5) are blocked and respiratory failure develops rapidly. – Brainstem. If intrathecal local anesthetic reaches this level, a block of sensory and motor nerves below the neck occurs. Additionally, dilated, nonreactive pupils result from a loss of parasympathetic efferent activity via the Edinger–Westphal nucleus. Hypoperfusion of the respiratory centers results in respiratory arrest. – Brain. Loss of consciousness results from diffusion of local anesthetic into the fourth ventricle. Flaccid jaw muscles result from blockade of the motor branch of trigeminal nerve in the rostral subarachnoid cisterns. • Cardiovascular effects – Vasodilation. Venous and arterial vessel dilation result in reduced preload/stroke volume (venous return) and afterload (systemic vascular resistance). – Bradycardia. Results from unopposed parasympathetic tone and blockade of the cardioaccelerator fibers arising from T1 to T4. Heart rate may also decrease as a result of a fall in right atrial filling. – Cardiac output is impaired due to a combination of reduced stroke volume and heart rate. – Cardiac arrest can result from hypotension and hypoxemia. • Cephalad spread depends on the local anesthetic dose, patient position and characteristics,

as well as technique. – Local anesthetic dose is determined by concentration, volume, baricity, and presence of vasoconstrictors. – Patient position is relevant in relation to the baricity (hyperbaric solution in Trendelenburg; hypobaric in reverse Trendelenburg). – Patient characteristics include height, age, gender, intra-abdominal pressure, and anatomical configuration of the spinal cord. – Technique includes type of needle, site of injection, direction of needle bevel, velocity of injection, and use of barbotage. • Pregnancy. Patients have increased intra-abdominal pressure and a diminished volume of the lumbar spinal canal due to distention of the epidural veins. A high spinal or total spinal may result in aspiration or present with severe fetal heart tone decelerations. • Blocks may continue to extend for at least 30 minutes after injection. • Although total spinals are often associated with epidural and spinal blocks, peripheral nerve blocks (e.g., brachial plexus interscalene blocks) have been implicated.

PREVENTATIVE MEASURES

• Local anesthetic infusion. Avoid rapid volume injection into the epidural space, avoid dural puncture, and use lower doses of local anesthetic if dural puncture is suspected. • Aspiration to rule out CSF. Should be performed prior to catheter insertion or bolusing through the epidural needle. A 3 cc syringe is more likely to detect CSF return compared to a 10 cc or larger syringe. Always check for negative aspiration prior to bolusing of local anesthetic. • Slow injection. Give local anesthetic in incremental doses (3 mL at a time) while continuously monitoring and assessing the patient for signs and symptoms of high spinal (in addition to assessing for local anesthetic toxicity). • Pregnant patients. Consider lower doses. • Check sensory level following boluses. Evaluate by assessing for loss of temperature sensation, pinprick, and inability to detect light touch. • Failed epidurals converted to spinal anesthetics are not associated with high blocks in one retrospective study of 61 patients. However, extra caution is required in the presence of any fluid in the extradural space (volume and time dependent). Consider a reduction in spinal dose or volume.

PREOPERATIVE ASSESSMENT • Symptoms, signs, and physical exam – Early recognition is key – Prior to hypotension, patient may complain of nausea or “not feeling well.” Tingling in the fingers indicates a high block at the T1 level or above. – Pulmonary. Early signs of apnea and hypoventilation include poor respiratory effort, whispering, and an inability to cough. Sudden respiratory arrest is due to hypoperfusion of the respiratory centers in the brainstem. – Cardiac. Hypotension and bradycardia, cardiovascular collapse, ventricular arrhythmias. – Neurologic. Sudden loss of consciousness, flaccid motor tone, dilated and nonreactive

pupils, high sensory block extending to cervical dermatomes, numbness, and weakness of hands. – Lack of recall of event is common • Diagnostic procedures – Aspiration of catheter reveals continuous clear or warm-to-touch fluid. – Laboratory analysis of aspirated spinal fluid is positive for serum level glucose. – Serum local anesthetic level may distinguish between total spinal and intravascular injection (not commonly performed in an acute setting).

DIFFERENTIAL DIAGNOSIS

• High spinal • Subdural blockade • Intravascular injection of local anesthetic • Cerebrovascular accident

TREATMENT • Prevention • Stop further local anesthetic administration, provide oxygen, immediately support ventilation, and prepare for intubation • Hemodynamics – Fluid bolus – Vasopressors – Inotropes – Trendelenburg positioning to treat hypotension may raise the level of the block and should be avoided. – Bradycardia can be treated with anticholinergic agents (atropine) or indirect stimulation of beta-adrenergic receptors (ephedrine)

FOLLOW-UP • Complete recovery to normal neurologic function is dependent on the dose of local anesthetic injected. A spinal anesthetic may start to regress after 1–2 hours, whereas an inadvertent epidural injection into the intrathecal space may result in a block lasting several hours (due to the increased amounts of local anesthetic injected). • Consider central line placement for monitoring and therapy if not already in place. • If hemodynamic stability returns, it may be appropriate to consider continuing with surgical procedure. • Patients should remain intubated and mechanically ventilated until the block regresses sufficiently (presence of airway reflexes, adequate spontaneous respiratory effort). Consider sedating the patient, as appropriate.

CLOSED CLAIMS DATA

• Of 1,480 claims for surgical or obstetric anesthesia using regional or epidural techniques,

high or total spinal block comprised 79 cases (5%). – Among the 79 high spinal cases, 16 patients died (20%), 23 had permanent disabling outcomes (29%), and 39 (49%) had temporary or nondisabling injuries, 1 with unknown outcome. Payment was made in 47 (59%) of the high block claims, with median payment of $753,500 (payment range: $15,700–$9,000,000).

REFERENCES

1. Dutton RP, Eckhardt WF, Sunder N. Total spinal anesthesia after interscalene blockade of the brachial plexus. Anesthesiology. 1994;80:939–941.

2. Park PC, Berry PD, Larson MD. Total spinal anesthesia following epidural saline injection after prolonged epidural anesthesia. Anesthesiology. 1998;89(5):1267–1270.

3. Pousman RM, Mansoor Z, Sciard D. Total spinal anesthetic after continuous posterior lumbar plexus block. Anesthesiology. 2003;98:1281–1282. 4. Ben-David B. Complications of regional anesthesia: An overview. Anesthesiol Clin North America. 2002; 20(3):665–667. 5. Lee LA, Posner KL, Cheney FW, et al. Complications associated with eye blocks and periopheral nerve blocks: An American Society of Anesthesiologists closed claims analysis. Reg Anesth Pain Med. 2009; 33(5):416–22. See Also (Topic, Algorithm, Electronic Media Element)

• Epidural • Combined spinal epidural • Spinal

CODES ICD9 995.22 ICD10 T88.59XA Other complications of anesthesia, initial encounter

CLINICAL PEARLS

• High spinals and total spinals are life-threatening complications of neuraxial anesthesia; however, morbidity and mortality is minimal when respiratory distress or apnea is recognized and treated immediately. • Iatrogenic and preventable. Slow initiation of neuraxial block with continuous monitoring of the patient and intermittent aspiration for CSF usually will prevent the progression to total spinal.

TRACHEAL AND CRICOTRACHEAL RESECTION Francisco Rivas-Doyague, MD Juan Moya-Amorós, PhD

BASICS DESCRIPTION General

• Resection remains the gold standard technique for the treatment of tracheal (Kuester operation) and cricotracheal stenosis (Pearson operation). The goals of surgical correction include ensuring normal breathing without tracheostomy and to facilitate proper oral nutrition and phonatory function. • After securing the airway and hyperextending the neck, the cervicotomy approach involves visceral compartment dissection down to the anterior surface of the trachea, while carefully avoiding the laryngeal nerves and other structures. The Kuester operation involves circumferential tracheal resection of the stenosis with subsequent end-to-end anastomosis (or “tracheal tugging”). The Pearson operation involves tracheal as well as anterior cricoid and possibly lateral arch resection followed by cricotracheal anastomosis. A sterile endotracheal tube (ETT) is inserted after tracheal opening. The average length of resection can range from 1.5 to 6 cm. • A partial or total sternotomy may be necessary when the area to be resected is distally located; on rare occasion a right thoracotomy may be warranted for juxtacarinal stenosis. • Benign etiologies – Inflammatory strictures and tracheoesophageal fistulas (TEF) in patients undergoing prolonged mechanical ventilation (endotracheal intubation) are the most frequent pathology requiring this intervention. – Traumatic injuries, idiopathic (less frequent). – Systemic diseases: Amyloidosis, Wegener’s disease (less common). • Malignant etiologies – Primary tracheal tumors (<0.1% of neoplasms): Squamous cell carcinoma, adenoid cystic carcinoma (cylindroma), carcinoid tumor. – Secondary tumors (local invasion): Thyroid, mediastinum, lung, esophagus. Position

• Supine with neck hyperextended; arms tucked. Padding materials should be placed under the glenoscapular area and between the scapular line. • Lateral decubitus positioning is utilized for the thoracotomy approach.

Incision

• Cervicotomy: Provides a good approach to the larynx and cervicothoracic trachea. • Partial/total sternotomy: Approach to distal segments of the trachea and carina. • Right thoracotomy (rare): For juxtacarinal stenosis.

Approximate Time 180–240 minutes EBL Expected <150 mL

Hospital Stay 10–15 days

Special Equipment for Surgery

• Sterile intubation tube • Montgomery T tube (occasionally). Device used as a combined tracheal stent and airway after surgery. It is an uncuffed silicone T-tube that can be inserted with the long limb in the trachea and the short limb projecting through the tracheostomy stoma. The extratracheal limb and/or upper open end of the intratracheal portion need to be occluded to prevent loss of volume during controlled ventilation. • Flexible/rigid bronchoscope

EPIDEMIOLOGY Prevalence

• Glottic and subglottic stenosis: 1.5–3% • Severe tracheal stenosis is rare, usually associated with previous tracheostomy, reaching up to 11% in the case of mild stenosis (with <10% of tracheal lumen reduction). • TEF <1%

Morbidity

• Up to 29% of minor complications require endoscopic treatment (granulomas, discrete stenosis). • Suture dehiscence 2.9%.

Mortality

• Tracheal resection: 2.4–4.5% • Cricotracheal resection: 1.6–5.5%

ANESTHETIC GOALS/GUIDING PRINCIPLES

Infection with Staphylococcus aureus methicillin-resistant or Pseudomonas aeruginosa is usual in patients treated with previous bronchoscopic procedures.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Inspiratory dyspnea and progressive stridor • Hoarseness and difficulties with expectorant (less frequent) • Asphyxial crisis after extubation

• Asymptomatic, incidental finding on bronchoscopy

History

• Prolonged intubation in ICU • Evaluation of previous endoscopic treatments • Emergency visits for dyspnea and stridor

Signs/Physical Exam

• Stridor with deep inspirations • Dysphonia (less common) • Tubal murmur increased on neck auscultation • If a tracheostomy is in place, an assessment of the stoma must be done: Size, location in relation to the midline, and presence of granulomas. MEDICATIONS

• Inhaled corticosteroids: Decrease in the inflammatory component of the mucosa • Mucolytics, to facilitate the removal of tracheobronchial secretions

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Coagulation studies • EKG, chest radiograph • Flexible bronchoscopy. Provides an assessment of stricture caliber, length, distance from the start to vocal cords, developmental stage (fibrosis, acute/subacute inflammation, tracheomalacia, TEF), and vocal cord mobility • Cervical CT scan (with sagittal reconstruction): To assess the actual length of the stricture. • Assessment of nutritional status

CONCOMITANT ORGAN DYSFUNCTION

• Dependent on the etiology of the ICU stay, and need for prolonged intubation or tracheostomy. • Neurological diseases. Altered mentation and the inability to cooperate can increase postoperative complications and may be a relative contraindication for surgery • Contraindications for surgery: Life expectancy <2 years.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Corticosteroids can reduce tracheal edema; prolonged high doses should be avoided as they can impair healing • Prokinetics, gastric secretion inhibitors may decrease aspiration risk. • Mucolytics and preoperative chest physiotherapy education.

Special Concerns for Informed Consent

• Need to maintain a Montgomery T-tube after intervention. • Dysphonia secondary to recurrent and/or superior laryngeal nerve injury. • Risk of wound dehiscence with the need for an urgent tracheotomy.

Antibiotics/Common Organisms

Amoxicillin – clavulanic acid 2 g q8 hours from the time of anesthetic induction and for 3 days after intervention. INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia • Regional techniques depending on the approach (e.g., epidural or paravertebral catheter for a thoracotomy approach).

Monitors

• Standard ASA monitors • Two large-bore peripheral veins catheters • Arterial line for beat-to-beat BPs and blood gas analysis. The left radial artery is preferred to avoid interferences in the event that the arterial brachiocephalic trunk is manipulated during surgery • Monitoring of the respiratory function: Pressure-volume curves, capnography, tidal volume. Mainstem intubation is common.

Induction/Airway Management

• Have the following available: ETTs of different caliber, including a 5.0 and 6.0; difficult airway equipment; and a pediatric fiberoptic scope • Tracheostomized patients. Induction may be carried out as usual, given the secured airway, followed by orotracheal intubation (OTI) with a small caliber tube. If it is not possible to insert the ETT past the stenosis, dilation with a rigid bronchoscope should be followed by armored tube placement. A sufficient anesthetic and muscle relaxation level should be achieved to avoid coughing as it could cause serious injury to the airway or bleeding. • Non-tracheostomized patients. The use of short-acting drugs is recommended, due to the potential for a difficult intubation. In patients with suspected difficulty, consider an awake FOI, or dilation with a rigid bronchoscope followed by armored tube insertion. For rigid bronchoscopy, anesthetic technique regarding oxygenation (jet ventilation, apneic oxygenation, positive pressure ventilation via a side port) and medications are surgeon, patient, anaesthetist, and institution- dependent. The goal should be to provide a sufficient anesthetic level, as coughing could cause serious injury to the airway or bleeding. Once the tracheal obstruction has been bypassed and the airway secured, long-acting muscle relaxant may be used.

Maintenance

• During surgical dissection, a gas inhalation technique may be used until the airway is

opened and secured from the operative field; at that time, it is necessary to convert to a total intravenous technique (TIVA) • A nasogastric (NG) tube should be placed prior to patient positioning to facilitate intraoperative identification of the esophagus (and for postoperative management). • Maintain direct access to the patient’s head. It may be necessary to provide short and intermittent periods of apnea while surgically entering the airway. A sterile endotracheal tube is inserted directly into the tracheal opening with the tip above the carina; the breathing circuit is attached to it (allows for continued delivery of tidal volumes, while minimizing interference in the surgical field). The orotracheal tube is pulled back but should remain below the vocal cords to facilitate repositioning when the sterile tube is removed. • The head will need to be maximally flexed during anterior surface trachea repair.

Extubation/Emergence

• Should be performed in the operating room with the surgical team present. • Ensure spontaneous respiration, full resolution of muscle relaxation, avoidance of coughing and bucking, and suctioning of tracheobronchial secretions prior to tube removal. • Postoperative ventilation maneuvers that require hyperextension of the neck are contraindicated. • Clinical evaluation of respiratory function should be continuously monitored for (e.g., absence of stridor).

FOLLOW-UP BED ACUITY

• The bed position should be maintained at 45°, and the neck flexed. Some centers attach the head to the bed with two pillows placed on both sides to prevent head movement. • Intermittent NG aspiration should be performed during the first 24–48 hours. When the debit is low (<100–150 mL/24 hours), it can be plugged into a collection bag 24 hours before being removed. • NPO until peristalsis is detected. An oral tolerance test with small sips of water through a straw is often performed. • Nebulized treatment every 4 hours for the first 24 hours, and then every 6–8 hours. Humidified air should be interspersed. ANALGESIA

• Analgesic requirements are low, except in sternotomy and thoracotomy approaches; consider epidural or paravertebral catheter placement for them. • A combination of nonsteroidal anti-inflammatory drugs and paracetamol is usually sufficient for the cervical approach. Opioids may be added, as appropriate.

COMPLICATIONS

• Glottic and subglottic edema (stridor, respiratory distress) should be treated with corticosteroids.

• Anastomotic dehiscence (subcutaneous emphysema, respiratory distress). Treatment is with bronchoscopic OTI (tip below the suture), surgical revision, and the possibility of tracheostomy at the suture site. • Arteriotracheal fistula 1–2% (cough, massive hemoptysis, respiratory distress, shock). Treatment is with OTI and surgical revision to isolate the focus ± arterial bypass. • Chronic complications include – Granulation tissue. Less frequent with the use of absorbable material; laser therapy – Restenosis. Treatment possibility: Reintervention, laser treatment, endoprostheses.

PROGNOSIS

The cure rate in tracheal stenosis is ∼93.7% and in cricotracheal stenosis 90.3%.

REFERENCES

1. Amorós JM, Ramos R, Villalonga R, et al. Tracheal and cricotracheal resection for laryngotracheal stenosis: Experience in 54 consecutive cases. Eur J Cardiothorac Surg. 2006;29(1):35–39. 2. Cameron D. Wright. Surgical management of subglottic stenosis. Operative Techniques in Cardiac & Thoracic Surgery. 2008;13(1):53–65. 3. Guha A, Mostafa M, Kendall JB. The Montgomery T-tube: Anaesthetic problems and solutions. Br J Anaesth. 2001;87(5):787–790. 4. Marques P, Leal L, Spratley J, et al. Tracheal resection with primary anastomosis: 10 years experience. Am J Otolaryngol. 2009;30:415–441. 5. Nirmal K. Veeramachaneni, Bryan F. Meyers. Surgical repair of iatrogenic cervical tracheal stenosis. Operative Techniques In Cardiac & Thoracic Surgery. 2008;13(1):40–52.

CODES ICD9 519.19 Other diseases of trachea and bronchus ICD10 J39.8 Other specified diseases of upper respiratory tract

CLINICAL PEARLS

• It is recommended to perform a flexible bronchoscopy for stenosis screening in all patients undergoing prolonged OTI and mechanical ventilation. • Stenosis shorter than 1 cm, without circumferential stenosis, and with residual cartilaginous support, as well as patients with multiple comorbidities may be managed with endoscopic dilation, carbon dioxide laser, or stent placement. However, these interventions may actually increase the severity of the lesion. • In TEF, surgery is the first option. • In the event of severe stenosis of the airway, first-line management is OTI with a small-bore

tube (5–6 mm) and dilation with rigid bronchoscopy in a specialized center. • Patients with Montgomery T tubes may present for follow-up procedures (e.g., granuloma removal) or other unrelated procedures and require special management.

TRACHEAL STENOSIS

Spyros D. Mentzelopoulos, MD, PhD Kalliopi Athanassiadi, MD, PhD Iosifina Kolliantzaki, MD

BASICS DESCRIPTION

• The adult trachea or windpipe is 9–15 cm long and consists of 15–20 C-shaped cartilages joined vertically by fibroelastic tissue and closed posteriorly by the unstrapped trachealis muscle (1). • The average, cross-sectional, inner diameter of the trachea is within 19–21 mm in adult men and 16–17 mm in adult women (2). • The Greek term “stenosis” means (abnormal) narrowing of its lumen. Symptoms are dependent on stenosis severity. EPIDEMIOLOGY Prevalence

• Acquired subglottic stenosis in adults and children: >80% result from prolonged endotracheal intubation and/or tracheostomy. • Among all intubated patients: 10–31%; <5% are symptomatic

Morbidity

Depends on stenosis severity, anatomical extent, and underlying pathology, as well as associated comorbid conditions, treatment strategy, and treatment-related complications. Mortality

Depends on etiology and stenosis morphology. Surgical treatment is associated with a periand/or postoperative disease-related mortality of 0–33%. ETIOLOGY/RISK FACTORS

• Congenital tracheal stenosis. Secondary to developmental abnormalities of the trachea or major intrathoracic vessels. • Acquired tracheal stenosis. Frequently related to orotracheal intubation or tracheostomy, and subsequent development of granulation tissue that matures to fibrous tissue. Cuff pressures of >30 mm Hg can obliterate capillary perfusion, with subsequent mucosal ulceration, chondritis, cartilaginous necrosis, development of granulation tissue, fibrous narrowing, and circumferential stenosis. The endotracheal tube (ETT) tip can also repeatedly impinge and traumatize the anterior or posterior tracheal wall; posterior wall trauma can lead to the formation of a tracheoesophageal fistula. PHYSIOLOGY/PATHOPHYSIOLOGY

• Respiratory flow characteristics. Laminar flow occurs when a fluid moves in a steady manner and in parallel layers. There is no mixing between adjacent layers, which slide smoothly past one another; it is akin to “homocentric fluid cylinders,” with the innermost flowing at maximum velocity (approximately double the overall, average velocity) and the outermost being immobile. • In fluid mechanics, the Reynolds number (Re) is a dimensionless ratio of the inertial-toviscous forces for given flow conditions. At an Re <2,300, flow is typically laminar; Re >2,300 results in fluid elements no longer traveling in straight lines with constant speed; and at an Re >4,000, motion becomes turbulent (random, chaotic, the air particles swirl in eddies, and there is a rapid variation of pressure and velocity in space and time). • With stenosis, the Re may exceed 10,000 and corresponds to higher, eddies-associated, kinetic energy dissipation. In addition, downstream to a stenotic segment, there may be a poststenotic expansion of the tracheal lumen, causing abrupt deceleration and/or separation of the tracheal airflow. The latter may result in a centerline jet surrounded by slowly turning eddies, which further augment the frictional energy dissipation. The stenosisinduced, resistive/frictional energy loss corresponds to a substantial increase in the work of breathing and can ultimately lead to respiratory decompensation, especially if stenosis severity increases with time. • Types. Depending on the nature and site of the stenosis, the obstruction can be inspiratory or expiratory; and fixed or variable. Flow limitation exists when inspiratory and/or expiratory flow reaches a plateau, before the completion of inspiration and/or expiration, respectively. This (maximal) plateau flow is independent of any further increase in patient effort. – Fixed obstruction. Describes a cross-sectional area of the stenotic segment that does not change during the respiratory cycle; it may cause both inspiratory and expiratory flow limitation, independent of its location. – Variable obstruction. Means that the cross-sectional area of the stenotic segment is partly dependent on the pressure difference across the tracheal wall, which in turn varies between the inspiratory and expiratory phase. Also, the timing of maximal collapsibility of the stenosis varies according to its location. In a variable extrathoracic stenosis located in the Upper third of the trachea. The intraluminal pressure drops below the extraluminal (atmospheric) pressure during inspiration, and the tracheal wall tends to collapse causing inspiratory flow limitation. Lower two thirds of the trachea (and/or the main bronchi). The extraluminal (intrathoracic) pressure exceeds the intraluminal pressure during expiration, and the airway wall tends to collapse causing expiratory flow limitation.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The narrowed airway may present unique challenges with respect to airway control and maintenance of ventilation. • A thorough knowledge of the nature (structural versus functional), severity (numerical code), and location of the tracheal stenosis, as well as the possible impact of any comorbid conditions, should be determined during the preoperative evaluation.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Can appear progressively or abruptly; includes exercise intolerance, hemoptysis. • At rest, symptoms may not develop until they have reached 70–75% stenosis (3). Cyanosis is a late sign, signalling complete airway obstruction (3). • Frequently confused with bronchial asthma; symptoms may be unresponsive to bronchodilators and may worsen in the supine position or during neck extension.

History

Prior airway interventions (e.g., orotracheal intubation and tracheostomy) and associated complications (e.g., airway trauma), surgery, or trauma involving the airway and/or the neighboring anatomical structures; and comorbid conditions Signs/Physical Exam

Brassy cough, wheezing progressing to exercise stridor, and superior vena cava syndrome TREATMENT HISTORY

Interventional bronchoscopic procedures employing: • Laser photoresection • Mechanical (e.g., balloon) dilatation • Stenting • Intraluminal brachytherapy (occasionally complemented by chemotherapy, and radiotherapy) • Tracheal surgery MEDICATIONS

• Topical application of mitomycin C • Intralesional long-acting corticosteroid injection

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC • Pulmonary function tests • CT and virtual bronchoscopy: Multidetector CT with coronal, sagittal, and 3-dimensional reconstruction and virtual bronchoscopy constitute the current state-of-the-art tools for evaluation of major airway stenoses. • MRI • Fiberoptic bronchoscopy

CONCOMITANT ORGAN DYSFUNCTION

• Congenital stenosis. May have vascular (pulmonary artery sling, anomalous origin of the innominate artery, or double aortic arch), cardiac (ventricular or atrial septal defect, or pulmonary atresia), or esophageal (proximal atresia with distal tracheoesophageal fistula)

anomalies as well as other (vertebral, anal, renal, and limb) deformities. • Adult tracheal stenosis. May have severe cardiac (congestive heart failure), respiratory (obstructive airways disease), and vascular (thoracic aortic aneurysm) comorbidities that increase morbidity/mortality.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Potential underlying comorbidities should be optimized prior to elective procedures. • Severe or worsening stenosis may warrant evaluation and treatment before proceeding with the surgical procedure.

CLASSIFICATIONS

• Numerical codes correspond to a specific range of% reduction in the cross-sectional area of the tracheal lumen: – 0: 0% – 1: <25% – 2: 26–50% – 3: 51–75% – 4: 76–90% – 5: 91%–complete obstruction • Stenosis type (4) – Structural (4 subtypes) Exophytic/intraluminal Extrinsic Distortion Scar/stricture – Dynamic/functional (2 subtypes): Damaged cartilage/malacia Floppy membrane • Stenosis location – Score I: Upper third of the trachea – Score II or III: Middle or lower third of the trachea – Score IV or V: Right or left main bronchus

TREATMENT PREOPERATIVE PREPARATION Premedications

• In patients with severe or dynamic stenosis, avoid any premedication that could potentially cause respiratory depression. • Antisialagogues may be given; however, the drying of secretions can aggravate the stenosis by causing a mucous plug. • Consider humidified oxygen, racemic epinephrine, and steroids, as appropriate.

Special Concerns for Informed Consent

Life-threatening intraoperative complications such as complete airway obstruction can occur. INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on the procedure and severity of stenosis. • Local and regional techniques should be considered when possible to avoid airway instrumentation and potential trauma/edema.

Monitors

Standard ASA monitors

Induction/Airway Management

• Adequate preoxygenation (e.g., administration of 100% O2 for 5–15 minutes during tidal

volume breathing) should precede induction. • A slow, inhaled volatile induction with maintenance of spontaneous ventilation may be considered until the airway is secured. • Alternatively, the use of short-acting IV anesthetics can be titrated to eyelid reflex, with concurrent bag-mask-assisted ventilation. • Have several ETT sizes available.

Maintenance

• An inhaled or an IV (e.g., propofol) anesthetic agent combined with an opioid (e.g., fentanyl and remifentanil) can be used. • Prepare for the possibility of airway collapsibility distal to the ETT tip with the use of external positive end-expiratory pressure (PEEP) to stabilize the major airway(s).

Extubation/Emergence

• Standard criteria apply. Aim for a smooth extubation. • If there was airway trauma at the time of induction, consider checking for a “leak” around the ETT, administering steroids, or keeping the patient intubated.

FOLLOW-UP BED ACUITY

Depends on the surgery, comorbidities, and intraoperative events. Patients who may have sustained airway trauma with airway management should be carefully observed and managed. MEDICATIONS/LAB STUDIES/CONSULTS

• Consider humidified oxygen, racemic epinephrine, diuretics, steroids, and antireflux medications, as appropriate. • Chest physiotherapy can aid with the clearance of secretions.

COMPLICATIONS

Airway trauma or edema

REFERENCES

1. llis H, Feldman S. The respiratory pathway. In: Ellis H, Feldman S, eds. Anatomy for Anaesthetists, 7th ed. Oxford: Blackwell Science Ltd, 1997:3–78.

2. Breatnach E, Abbott GC, Fraser RG. Dimensions of the normal human trachea. AJR Am J Roentgenol. 1984;142:903–906. 3. edley TJ, Drazen JM. Aerodynamic theory. In: Comprehensive Physiology, Supplement 12: Handbook of Physiology. The Respiratory System, Mechanics of Breathing. Wiley online library, DOI: 10.1002/cphy; accessed at http://onlinelibrary.wiley.com/book/10.1002/cphy/toc. 4. Freitag L, Ernst A, Unger M, et al. A proposed classification system of central airway stenosis. Eur Respir J. 2007;30:7–12.

ADDITIONAL READING

• Mentzelopoulos SD, Tzoufi MJ. Anesthesia for tracheal and endobronchial interventions. Curr Opin Anaesthesiol. 2002;15:85–94.

See Also (Topic, Algorithm, Electronic Media Element) • Pulmonary function tests • Tracheostomy • Laminar flow • Tracheal and cricotracheal resection

CODES ICD9 • 519.19 Other diseases of trachea and bronchus • 748.3 Other anomalies of larynx, trachea, and bronchus ICD10 • J39.8 Other specified diseases of upper respiratory tract • Q32.1 Other congenital malformations of trachea

CLINICAL PEARLS

• The trachea extends from the inferior border of the cricoid cartilage (level of 6th cervical vertebra) to its bifurcation (level of 5th–6th thoracic vertebra in the erect position) (1). The upper third of the trachea is extrathoracic (i.e., lies above the suprasternal notch); it lies within the pretracheal fascia that also contains the thyroid, esophagus, and recurrent laryngeal nerves (1). The lower two-thirds of the trachea are intrathoracic. • As a central mediastinal structure, the lower trachea is encircled by the aortic arch, left recurrent laryngeal nerve, esophagus, right vagus nerve and azygos vein, and superior vena

cava (1).

TRACHEOESOPHAGEAL FISTULA REPAIR Ellen Y. Wang, MD

BASICS DESCRIPTION General

• A tracheoesophageal fistula (TEF) is a congenital or acquired communication between the trachea and esophagus. The specific cause is not known, but involves separation failure of the foregut into the esophagus and trachea during embryologic development. TEFs are typically associated with esophageal atresia (EA) and other congenital abnormalities, especially the VACTERL syndrome, which involves three or more of the following: – Vertebral anomalies: Hemivertebrae, vertebral fusion, scoliosis (incidence 17%) – Anorectal anomalies: Imperforate anus, cloacal deformities (12%) – Congenital heart disease: Ventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, atrial septal defect, atrioventricular canal, coarctation of the aorta, and right-sided aortic arch (20–25%) – Tracheoesophageal fistula – Esophageal atresia – Renal abnormalities: Renal agenesis or dysplasia, horseshoe kidneys, ureteral malformations (16%) – Limb abnormalities: Radial dysplasia, absent radius, syndactyly, polydactyly (10%) • Other associated syndromes include DiGeorge, Pierre–Robin, Holt–Oram, CHARGE, or polysplenia • Acquired TEFs are rarer than congenital anomalies, and occur secondary to malignancy, inflammatory processes, corrosive ingestion, or traumatic injury. Although uncommon, TEFs can occur with prolonged mechanical ventilation with an endotracheal tube. • Primary repair involves isolation and ligation of the fistula and primary anastomosis of the esophagus. • If the infant is unable to withstand primary repair (due to low birth weight, pneumonia or other congenital anomalies), a gastrostomy can be performed first to decompress the stomach and minimize regurgitation into the lungs, and a central line may be placed for parenteral nutrition. • If the esophagus has a long gap (>3 cm), there are several options: – Delayed primary repair to allow growth of the esophagus – Serial dynamic lengthening to stretch the esophagus – Gastric pull-up – Esophageal replacement where a segment of bowel or stomach may be interposed to bridge the gap Position

• Supine, for assessment of fistula with rigid bronchoscopy or tracheoscopy (1), possible

Fogarty balloon catheter placement in fistula. • Left lateral decubitus position for right thoracotomy approach; right lateral decubitus for left thoracotomy.

Incision

• Right-sided thoracotomy; left-sided if there is a right-sided aortic arch (2.5%) (2). • An extrapleural approach to the posterior mediastinum is used whenever possible. • Alternatively, a thoracoscopic transpleural approach may be chosen. • A right cervical neck dissection may occur for high H-type TEF (70% of H-types) (3).

Approximate Time

2–4 hours for primary repair EBL Expected Minimal

Hospital Stay

Weeks to months

EPIDEMIOLOGY Prevalence

• 1:3,000–4,000 live births; 20–30% of infants are premature • 90% of TEF is associated with EA • Types of TEF (Gross/Vogt classification) (3) – Type A/II – Isolated EA, no fistula to trachea: 4–7% of cases. – Type B/IIIa – EA, proximal end connected to trachea, blind distal pouch. – Type C/IIIb – EA with blind proximal pouch, distal end connected to the trachea: ~90% of cases – Type D/IIIc – EA, both proximal and distal ends connect to trachea. – Type E/H-type – Isolated TEF, with continuous esophagus and fistula with trachea: 4% of cases. – Type F – Esophageal stenosis.

Morbidity/Mortality

• Typically, survival rate is >90% • Okamoto classification (2009) (2) – I: birth weight >2 kg, no major cardiac anomaly (survival 100%) – II: birth weight <2 kg, no major cardiac anomaly (survival 81%) – III: birth weight >2 kg and major cardiac anomaly (survival 72%) – IV: birth weight <2 kg and major cardiac anomaly (survival 27%)

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Avoidance of aspiration is of utmost importance. The patient should be kept NPO, in a semiupright position to prevent reflux, and have intermittent/continual suctioning of the upper pouch.

• Avoidance of positive pressure ventilation, especially before Fogarty balloon catheter placement or fistula ligation. Gastric distention from high airway pressures through the fistula decreases functional residual capacity, impairs ventilation/oxygenation, and increases the risk of aspiration.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Preexisting lung disease from aspiration or respiratory distress syndrome due to prematurity. • Other prematurity conditions: Hypoglycemia, hypocalcemia, apnea/bradycardia, and anemia.

History

• Should be suspected in maternal polyhydramnios, where EA prevents swallowing of amniotic fluid. • After birth, the infant typically presents with increased oral secretions, gagging, cyanotic spells, coughing relieved by suctioning, regurgitation exacerbated by feedings, and inability to pass the suction catheter more than 9–10 cm into the esophagus. • Recurrent pneumonias are associated with H-type TEF, which can be diagnosed later in life. • Prior to surgery, dextrose-containing fluids should be given to prevent dehydration and hypoglycemia, acid–base abnormalities corrected, and respiratory status optimized.

Signs/Physical Exam

• May have low birth weight • Respiratory distress leading to mechanical ventilatory support • Abdominal distention may occur due to air in the stomach • May have a sacral dimple

MEDICATIONS

A thorough medication history should be obtained, including vasopressor and sedation use, recent transfusion history, and allergy history. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Plain radiograph reveals air in the stomach, radiopaque contrast in a blind esophageal pouch, or coiling of an OG tube in the upper pouch of patients with EA. • Direct visualization with endoscopy or bronchoscopy may be used, particularly in the diagnosis of acquired TEFs. • Baseline chest, abdomen, pelvis and spine radiographs, echocardiogram, and renal and lumbar ultrasonography should be obtained. • Preoperative hematocrit, electrolytes, glucose, BUN, and Cr should be obtained.

CONCOMITANT ORGAN DYSFUNCTION

• Congenital heart disease is present in 20–25% of TEFs.

• Coexisting anomalies are most common in isolated EA and least common in isolated TEF.

TREATMENT PREOPERATIVE PREPARATION Premedications

Not usually necessary

Special Concerns for Informed Consent

• Postoperative ventilation and ICU care • Possible blood transfusion

Antibiotics/Common Organisms

Prophylactic antibiotics aimed to reduce the risk of respiratory infection. INTRAOPERATIVE CARE Choice of Anesthesia

General anesthesia with an endotracheal tube, with or without epidural catheter placement Monitors

• Standard ASA Monitors. Both preductal and postductal pulse oximeters may be necessary. • Good peripheral IV access (usually 2 large-bore IVs). Consider central venous catheter placement if peripheral IV access is unsatisfactory. • An arterial line, right radial (preductal) or umbilical, is preferred for close monitoring of blood gases and continuous BP monitoring. • A Foley catheter to assess fluid status. • A precordial stethoscope may be helpful in detecting intraoperative airway obstruction.

Induction/Airway Management

• Suction the proximal esophageal pouch prior to induction • Consider awake intubation • Alternative approach would be mask induction with maintenance of spontaneous ventilation (or gentle positive pressure ventilation) with adjunct IV medications (propofol, fentanyl, ketamine). This method is commonly chosen if a bronchoscopy is done first for placement of a Fogarty balloon catheter to occlude the fistula. • At the end of rigid bronchoscopy, the ETT can be placed under direct visualization. Alternatively, the ETT can be placed in the right mainstem bronchi and withdrawn slowly until bilateral breath sounds are heard. A cuffed tube may be used to occlude the TEF. Position can be confirmed with a fiberoptic scope. Left mainstem intubation may be necessary if the fistula is below the carina (11% cases) (2). • After intubation, careful attention must be paid to positioning the tube tip distal to the fistula so that the lungs are ventilated and the stomach is not distended in order to decrease the risk of reflux of gastric contents into the lungs. The endotracheal tube position must be checked after positional changes.

Maintenance

• Balanced technique with volatile anesthetics, oxygen +/– air, narcotics, and a neuromuscular relaxant. Avoid nitrous oxide. Titrate the FiO2 to maintain a preductal SpO2

>95%. • A combined general/regional technique may be considered to facilitate early extubation with an epidural placed after the airway is secured, assuming there are no vertebral anomalies. The catheter can be inserted at the thoracic/lumbar level or caudally and advanced to T6–T7. An epidurogram can confirm tip position. • Adequate oxygenation/ventilation may be a struggle, as a result of the following: – Lung retraction can impair ventilation, and intermittent release of retraction may be necessary to allow reinflation of the lung. – Blood clots and secretions can plug the endotracheal tube, and frequent suctioning may be required. – Surgical manipulation of the trachea can cause manual obstruction. – Dislodgement of the Fogarty balloon catheter can occlude the trachea. – Air leakage through the fistula can result in inadequate ventilation; gastric distention can lead to aspiration or impaired ventilation. • Manual ventilation may be necessary in small neonates, especially during surgical manipulation of the lungs causing variable lung compliance. • Volume maintenance with crystalloid-containing dextrose is usually adequate, as blood loss is minimal. Premature infants that are anemic may need blood transfusions. It is important to avoid fluid overload, which can cause pulmonary edema. • Intermittent blood gas monitoring should follow pH, pO2, pCO2, hematocrit, glucose, and electrolytes as needed, especially in thoracoscopic cases when end-tidal CO2 measurements

may not be accurate. • Temperature regulation is very important in neonates. Attempts should be made to keep fluids and ambient room temperature warm.

Extubation/Emergence

• In healthy infants with a simple TEF repair, extubation may be possible at the end of the case. However, the benefits of extubation must be weighed against the risk of reintubation and compromise of the repair. • Most infants will remain on ventilatory support for at least 24–48 hours postoperatively, with avoidance of bag mask ventilation for several days postoperatively to prevent stress at the esophageal suture lines. • Long gap EA repairs will require longer periods of ventilatory support.

FOLLOW-UP BED ACUITY

• ICU monitoring is required • Postoperative suctioning should be carefully done, with catheters marked to avoid insertion past the anastomosis.

• Excessive neck extension should be avoided to minimize tension on the suture lines. • Neuromuscular blocking agents may be used to suppress spontaneous ventilation.

ANALGESIA

Continuous opioid infusions or epidural analgesia COMPLICATIONS

• Leak or strictures at the anastomosis or fistula site, esophageal reflux and dysmotility • Recurrent upper and lower respiratory infections, tracheomalacia, recurrent fistulas • Scoliosis and chest wall deformities from postthoracotomy syndrome

PROGNOSIS

Respiratory (obstructive and restrictive ventilatory defects, airway reactivity, and pneumonia) and GI complications (reflux, dysphagia, dysmotility) may persist throughout life, and subsequent visits to the operating room are common.

REFERENCES

1. eanovic D, et al.Tracheoscopy assisted repair of tracheo-esophageal fistula (TARTEF): A 10year experience. Pediatr Anaesth. 2007;17(6):557–562. 2. Broemling N, Campbell F. Anesthetic management of congenital tracheoesophageal fistula. Pediatr Anaesth no. doi: 10.1111/j.1460-9592.2010.03377.x 3. childi O, Grewal H. Congenital anomalies of the esophagus. Otolaryngol Clin North Am. 2007;40(1):219–244, viii. 4. pitz L.Oesophageal atresia. Orphanet J Rare Dis. 2007;11:2–24.

ADDITIONAL READING

• Holzman RS, Mancuso TJ, Polaner DM. A Practical Approach to Pediatric Anesthesia, Chapter 14. Lippincott Williams & Wilkins, 2008.

See Also (Topic, Algorithm, Electronic Media Element) • Preterm infant • Pediatric cardiac physiology • One lung ventilation

CODES ICD9 • 530.84 Tracheoesophageal fistula • 750.3 Tracheoesophageal fistula, esophageal atresia and stenosis ICD10 • J86.0 Pyothorax with fistula • Q39.1 Atresia of esophagus with tracheo-esophageal fistula

• Q39.2 Congenital tracheo-esophageal fistula without atresia

CLINICAL PEARLS

• Repair of TEF/EA in the neonate can present numerous challenges, and careful preoperative planning and communication with the surgeon are essential in treating these patients. • Other challenges are inherent in the care of a neonate, including difficult venous and arterial access, volume and electrolyte management, and temperature regulation.

TRACHEOSTOMY Kelly Bruno, BS, MD

BASICS DESCRIPTION General

• Tracheostomy is a surgical airway obtained by incision directly through the anterior wall of the trachea, followed by insertion of a tracheostomy or endotracheal tube (ETT). • Indications – Upper airway obstruction such as head or neck tumor, angioedema, epiglottitis, vocal cord dysfunction, severe sleep apnea. – Severe facial or nasal trauma, edema, or subcutaneous emphysema. – Pulmonary toilet in patients with poor control over airway secretions or inability to cough, as seen in cerebrovascular disease or muscular disorders. – Patients requiring long-term mechanical ventilation (especially if longer than 14 days). – “Cannot ventilate, cannot intubate” emergency scenario. Additionally, patients may present with an emergently placed cricothyroidotomy that needs to be converted to a more stable airway. • Advantages of a tracheostomy tube – Improves breathing efficiency by reducing dead space by ∼150 mL. – Improved comfort (bypasses oropharyngeal and hypopharyngeal gag reflexes). – Allows patient to talk and consume food. – Decreases the work of breathing • Disadvantages of a tracheostomy tube – Bypasses the upper airway that normally humidifies, warms, and filters air. – Increased mucus production in response to dry tracheal and bronchial epithelium can occlude tracheostomy tube. • Tracheostomy placement techniques – Surgical technique (ST) approach. Landmarks commonly identified include the suprasternal notch and the upper borders of the cricoid and thyroid cartilage. Local anesthetic with vasoconstrictor (to decrease bleeding) is infiltrated into the Jackson’s triangle (bordered inferiorly by the suprasternal notch, laterally by the sternocleidomastoid muscles on either side, and superiorly by the cricoid cartilage). A midline vertical incision (∼2–3 cm) is made from the lower border of the cricoid cartilage to the suprasternal notch (some clinicians perform a 2–3 cm transverse incision over the 2nd tracheal ring) through the skin and subcutaneous tissue. Bleeding vessels are cauterized or ligated to improve visualization and prevent blood from entering the airway. Retractors are used to aid with visualization during subsequent blunt dissection down to the tracheal ring; the thyroid isthmus often requires upward retraction. Entry into the trachea can be performed with a vertical, midline incision between the 2nd and 3rd

tracheal rings to allow for insertion of an appropriately sized, lubricated tracheostomy tube. Stay sutures are inserted into the trachea, one on either side of the midline, and sutured to the skin to aid with dissection and recannulation should the tracheostomy tube become dislodged after early placement. The tracheostomy tube is secured to the skin. – Percutaneous tracheostomy (PCT) approach. Can be performed at the bedside in the intensive care unit (ICU) or in the operating room by a trained clinician. Benefits of PCT compared to ST are that it is cost-effective, quicker, and easier to learn; it can also be performed at the bedside and can decrease the risk associated with transporting a critically ill patient. Multiple techniques have been described in the literature. The Ciaglia technique is commonly performed; it uses a wire inserted between the 1st and 2nd or 2nd and 3rd tracheal rings as a guide over which sequential dilators are forced through the tracheal wall to create a stoma of appropriate size.

Position

• The patient is positioned supine with the neck extended. Sterile prep is usually performed from the mandible above to the nipples below. – A shoulder pad placed under the patient’s shoulders can be used to obtain adequate neck extension. – A head ring should be used to stabilize the patient’s head. – Cervical disease or unstable spine may preclude extension and optimal positioning.

Incision

• ST approach. A standard 2–3 cm transverse or vertical incision over the 2nd tracheal ring. • PCT approach. The skin overlying the appropriate tracheal ring is punctured with an IV catheter.

Approximate Time

• ST: 15–35 minutes • PCT: 5–15 minutes

EBL Expected Minimal

Hospital Stay

Dependent on the underlying condition. Often performed in situations that require extended mechanical ventilation. Special Equipment for Surgery

• Surgical or PCT kit • Tracheostomy tube • Fiberoptic bronchoscopy for guidewire placement in Ciaglia PCT (if desired)

EPIDEMIOLOGY Prevalence

One of the most commonly performed ICU procedures. Rates of tracheostomy intervention,

however, vary widely in ICUs across the US due to ambiguous evidence-based studies. Prevalence

Increasing with improved critical care. Morbidity

• Intraoperative: Hemorrhage, air embolism • Immediate postoperative: Blocked or displaced tube, pneumothorax, subcutaneous emphysema, pneumonia, tracheal infection. • Delayed postoperative: Subglottic or tracheal stenosis, tracheocutaneous fistula, tracheal obstruction due to growth of granulation tissue, tracheoarterial fistula causing massive hemorrhage (appear to be more frequent with ST). • Studies suggest that PCT is associated with a higher incidence of short-term complications when compared to ST. These include tracheal lacerations, tracheoesophageal fistulas, and paratracheal insertion. Mortality

Most common causes of death are hemorrhage and displaced tube. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Work of breathing is comprised of the sum of elastic and resistive work. Tracheostomies can decrease the resistive component due to decreased length and improved ability to suction (decreased resistance) compared to endotracheal tubes. Additionally, there is improved efficiency due to the bypassing of anatomical deadspace from the upper airway passages (nose, mouth, pharynx). • Preoperative assessment should include the tracheostomy indication, physiologic status, and physical abnormalities of the head, neck, and throat. Tracheostomy placement for long-term mechanical ventilation should not be performed in hemodynamically unstable patients. • In situations where airway obstruction may be present, consider reviewing CT, fiberoptic, and laryngoscopy findings, if available. • The incidence of airway fires may be decreased by reducing the FiO2.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Airway obstruction: Agitation, cyanosis, changes in consciousness, choking, confusion, difficulty breathing, gasping for air, panic, wheezing. • Cerebrovascular disease: Paralysis, numbness, tingling, changes in vision, slurred speech, inability to speak, difficulty swallowing, loss of balance or coordination, changes in personality or mood, drowsiness, unconsciousness. • Facial or nasal trauma: Changes in sensation over facial distribution, deformed facial or nasal bones, missing teeth, double vision, difficulty breathing.

History

• Patients typically present with upper airway obstruction, significant upper airway

secretions, or the need for long-term mechanical ventilation. • For elective tracheostomies, take a full history and discuss previous exposures to anesthesia. • For emergency tracheostomies or those performed in the ICU, review the patient’s history with particular attention to indications of hypoxemia, hypovolemia, hypotension, and acidosis.

Signs/Physical Exam

• Identify potential difficulties with placement such as obesity, short neck, subcutaneous emphysema, and edema • Airway obstruction: Decreased breath sounds, rapid, shallow, or slowed breathing • Cerebrovascular disease: Muscle weakness, changes in neurological exam • Facial or nasal trauma: Bleeding from nose, eyes, mouth, lacerations, periorbital bruising, and edema

MEDICATIONS

Do not administer anticoagulants for the duration of the procedure to reduce the risk of bleeding at the incision site or into the airway. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

Hematocrit and coagulation factors: Consider assessment if there is clinical evidence (or suspicion) of a coagulopathy. Platelet count should be at least 50,000/μL. Patients with severe coagulopathies should not undergo a PCT. CONCOMITANT ORGAN DYSFUNCTION

• Varies based on the indication for a tracheostomy and must be assessed on an individual basis. • Patients requiring tracheostomy for long-term assisted ventilation in a critical care setting often have higher morbidity and mortality.

TREATMENT PREOPERATIVE PREPARATION Premedications None

Special Concerns for Informed Consent

• A consent form should be signed by a conscious patient for elective tracheostomies. • Informed consent is excused (implied consent) in emergency situations involving an unconscious patient. Antibiotics/Common Organisms

Prophylactic antibiotics for common skin pathogens

INTRAOPERATIVE CARE Choice of Anesthesia

• ST is usually performed under general endotracheal anesthesia (in situ or de novo). In tenuous airways (e.g., upper airway obstruction), where maintenance of spontaneous ventilation is mandatory, mild or no sedation may be necessary. Vasoconstrictors are used in both circumstances. • PCT is usually performed under general endotracheal anesthesia.

Monitors

Standard ASA monitors

Induction/Airway Management

• Patients who require a tracheostomy for long-term mechanical ventilation often have an ETT in situ. • Patients with upper airway obstruction or otherwise suspected difficult airway may be considered for: – Fiberoptic bronchoscopy and ETT placement (awake or asleep). When awake, topical anesthesia, with minimal or no sedation, and supplemental oxygen. Consider using a small ETT if tracheal compression is suspected. – Tracheostomy placement without placing an ETT while keeping the patient SV. Minimal or no sedation and supplemental oxygen is administered. • In the event of a “cannot ventilate, cannot intubate” scenario consider the placement of an LMA, two-handed mask ventilation, supraglottic jet ventilation, or awakening the patient while surgical access is attained. Maintenance

• Local anesthetic agents and vasoconstrictors are injected at the incisional site and subcutaneous tissue (decreases pain and bleeding via vasoconstrictors) • If sedation with SV is performed, may be maintained with opioids, propofol, ketamine, or dexmedetomidine. These should be cautiously titrated, if used. • General anesthesia may be maintained with inhalational or total IV anesthesia. Muscle relaxation is not necessary for surgical exposure – Prior to surgical entry into the trachea, the FIO2 should be decreased, as tolerated, to

avoid an airway fire (add air to fresh gas flows). Additionally, tidal volumes and peak inspiratory pressures should be noted for postoperative comparison with the newly placed tracheostomy tube. – Surgical entry into the trachea with a scalpel often results in puncture of the ETT cuff; may be avoided by deflation of the cuff and pulling back (not out) the ETT. In the event of a difficult or impossible reintubation, consider the use of a tube exchanger through the ETT to aid with reinsertion, if the tracheostomy becomes difficult.

Extubation/Emergence

• Once the tracheostomy tube is in place, the ventilator is connected. End-tidal carbon dioxide, tidal volumes, and peak pressures are confirmed to ensure proper placement.

• With the ventilator attached, the tracheostomy tube is secured with tape or ties. • The patient is extubated if the tracheostomy tube is placed successfully.

FOLLOW-UP BED ACUITY

• Typically ICU to allow for routine cleaning of the tracheostomy tube, inner cannula, and stoma along with maintenance of proper humidity in order to prevent life-threatening conditions like tube dislodgement or occlusion of tube. • Regular suctioning should be performed as directed by the tube manufacturer to maintain patency. • Skin around the stoma can be cleaned with hydrogen peroxide then rinsed with normal saline. ANALGESIA

• Acetaminophen • Opioid • Local infiltration

COMPLICATIONS

• Hemorrhage. The innominate artery crosses anteriorly, from left to right, at the superior thoracic inlet, beneath the sternum. • Stomal cellulites, tracheal infections • Subcutaneous emphysema, pneumomediastinum • Pneumothorax • Luminal stenosis • Dislodged or occluded tracheostomy tube • Tracheoesophageal fistula • Nerve damage. The recurrent laryngeal nerves may be damaged if dissection deviates from the midline.

REFERENCES

1. Chew J, et al. Tracheostomy: Complications and their management. Arch Otolaryngol. 1972;96(6):538–545. 2. Dempsey GA, Grant CA, Jones TM. Percutaneous tracheostomy: A 6 year prospective evaluation of the single tapered dilator technique. Br J Anaesth. 2011;105:782–788. 3. Durbin C. Techniques for performing tracheostomy. Resp Care. 2005;50(4):488–496. 4. Fikkers BG, et al. Emphysema and pneumothorax after percutaneous tracheostomy: Case reports and an anatomic study. Chest. 2004;125(5):1805. 5. Kakar P, et al. Percutaneous dilatation tracheostomy in critically ill patients with documented coagulopathy. Crit Care. 2008;12:334. 6. King C, Moores LK. Controversies in mechanical ventilation: When should a tracheotomy

be placed? Clin Chest Med. 2008;29:253–263. 7. Trouillet JL, et al. Early percutaneous tracheotomy versus prolonged intubation of mechanically ventilated patients after cardiac surgery: A randomized trial. Ann Intern Med. 2011;6:373–383. See Also (Topic, Algorithm, Electronic Media Element) • Cricothyroidotomy • Difficult airway • Airway fire • Jet ventilation • Laminar flow

CODES ICD9 V44.0 Tracheostomy status ICD10 Z93.0 Tracheostomy status

CLINICAL PEARLS

• ST may also be performed at the patient’s bedside to avoid transporting a critically ill patient. The anaesthetist should have all medications and airway equipment available and ready.

TRANSCRANIAL DOPPLER Paul Kerby, MB, BS Selma Ishag, MB, BS, MD

BASICS DESCRIPTION

• Transcranial Doppler (TCD) studies provide a noninvasive, real-time method of assessing cerebral hemodynamics. • TCD measurements and utility are based on the concept that velocity is inversely related to the area of the artery’s lumen; vasospasm narrows the lumen and hence results in increased velocity. • It may be used as an indirect measure of blood flow and to evaluate the state of cerebral autoregulation. PHYSIOLOGY PRINCIPLES

• TCD ultrasonography utilizes the principle that sound waves transmitted at a certain frequency will be reflected back at a different frequency as a result of relative motion between the source and the receiver. • TCD signal frequency remains constant in soft tissues but changes according to the motion of red blood cells (RBCs) in their path. The difference in frequency between the transmitted and reflected waves is the Doppler shift. • The Doppler shift is affected mainly by the velocity of blood flow and the angle of insonation (the angle between the ultrasound beam and the blood flow direction). • “Gating” is changing the depth of interrogation. This allows for measurements at different loci along the longitudinal axis of the vessel. • At low frequency (2 MHz), the attenuation of signals by the skull and soft tissues is less than with conventional Doppler instruments (5–10 MHz) • Pulsed ultrasound waves are directed at intracerebral arteries through acoustic windows (see Anatomy). • Cerebral blood flow velocity (CBFV) is calculated and displayed against time. Three velocities are calculated: – Peak systolic velocity (PSV) derived from the waveform – End-diastolic velocity (EDV) derived from the waveform – Mean velocity (FVm) = (PSV + [EDV × 2]) / 3 is considered the best indicator. • The pulsatility index (PI) and resistance index (RI) are also calculated. The PI is directly related to the difference in the systolic and diastolic velocity and inversely related to the mean velocity. PI = (PSV − EDV)/FVm. Normal values range from 0.85–1.10 and are influenced by the blood pressure, partial pressure of carbon dioxide, and vessel compliance (it is not influenced by the angle of insonation). RI, as its name implies, is also a reflection of vascular resistance. ANATOMY

Acoustic windows are found at natural foramina or thin areas of the skull where the sound wave can penetrate more easily. There are three natural acoustic windows: • Transtemporal: Above the zygomatic arch. Insonates the arteries in the Circle of Willis (middle, anterior, and posterior cerebral arteries—MCA, ACA, and PCA). After identification of the MCA, the artery is followed to the bifurcation of the internal carotid artery into the MCA and ACA. Blood flow in the MCA is toward the probe and the Doppler signal is depicted above the zero line, while the ACA signal is below the zero line. • Transorbital: Over the eyelid. Insonates the ipsilateral carotid siphon and its collateral ophthalmic artery. Possibility of scanning for contralateral MCA and ACA. • Transforaminal (or suboccipital): Between the atlas and the base of the skull. Scanning of vertebral arteries and basilar artery potentially up to its bifurcation into the PCA.

PHYSIOLOGY/PATHOPHYSIOLOGY

• A mean FV (FVm) >120 cm/s can be caused by – Vasospasm – Hyperemia – Increased PaCO2 – Arterial stenosis – Increased age – Volatile anesthetics • Causes of decreased FV can be caused by – Hypotension – Increased ICP – Decreased PaCO2

– Pregnancy – IV anesthetics (excluding ketamine) – Hypothermia – Brain death • Increased PI and RI can be seen by – Increased ICP – Hydrocephalus – Traumatic brain injury – Intracerebral hemorrhage – Stroke – Brain death • Subarachnoid hemorrhage (SAH) – Vasospasm typically occurs in the large arteries at the base of the brain within 7 days following a SAH. It is thought to be secondary to the presence of extravasated blood. – Depending on the diagnostic tool and frequency of testing, the incidence of vasospasm is almost 100% but is symptomatic in only 20–30% of cases (described as delayed ischemic deficit [DID]). – TCD was shown to detect vasospasm 2.5 days before the appearance of DID and can potentially improve patient outcomes if early intervention is implemented. – To detect vasospasm, TCD utilizes the principle that the velocity of blood flow in an artery

is inversely proportional to the cross-sectional area of that artery. – A mean MCA flow velocity (FVm) >120 cm/s is abnormal and >200 cm/s corresponds to severe vasospasm. – To differentiate between increased systemic flow velocities in the ipsilateral ICA and vasospasm, the Lindegaard Ratio (LR) is used (FVMCA/FVICA). If the FV is elevated, then the LR value indicates the following <3 hyperemia 3–6 mild vasospasm >6 severe vasospasm – TCD measurements can be repeated at the bedside daily or more frequently as part of a comprehensive protocol for vasospasm detection and management. – Although it can aid in the diagnosis of vasospasm, the effect of TCD on improving patient outcome has not yet been established. • Stroke prevention in sickle cell disease (SCD) – There is Class I evidence that supports the use of TCD for assessing the risk of stroke in children with SCD. – Children with SCD are at risk of progressive occlusion of large intracranial arteries (ICA and MCA). – Mean FV >200 cm/s is considered abnormal and requires transfusion to lower hemoglobin S concentration (below 30%). • Stroke risk assessment – The benefit of carotid artery revascularization to prevent stroke in asymptomatic patients with carotid artery disease has not been clearly defined. To that extent, the presence of embolic signals in the MCA is being studied as a predictor of risk of stroke. – Asymptomatic patients with microembolic signals (MES), have a 15.6% risk of stroke compared to 1% risk of those who do not. – Thus, TCD may be useful in the selection of high-risk asymptomatic patients to undergo carotid revascularization. • Stroke treatment – The rate of recanalization is increased when TCD monitoring is utilized during thrombolysis; this is possibly due to improved exposure of the clot to thrombolytics. – Microbubbles injected with thrombolytics increased the rate of recanalization. • Traumatic brain injury – TCD may have a role in the assessment of ICP, cerebral autoregulation, and vasospasm. – ICP: Intracranial hypertension is associated with increased PI. TCD may have a role in ICP estimation in patients with stroke, liver failure, preeclampsia, and other conditions where the use of invasive ICP measurement has not been established. – Autoregulation: Cerebral autoregulation maintains a constant CBF at MAP between 60 and 160 mm Hg. Loss of autoregulation is common after TBI. Whether a change in FV reflects changes in BP and CO2 levels is being studied as an indicator of an intact autoregulation. – Vasospasm: FV decreases during the first 48 hours and then increases for the following 72 hours. The increase may represent vasospasm or hyperemia. Using LR, the cause can be distinguished, potentially improving patient management. • Brain death: Can serve as a tool to demonstrate cerebral circulatory arrest. Patients must

have demonstrated flow before death, as 8% of the population lack acoustic windows. Three waveforms are associated with arrest: Oscillating flow, small systolic spikes, and no signal.

PERIOPERATIVE RELEVANCE

• Carotid endarterectomy (CEA) – TCD is useful in monitoring for cerebral ischemia during CEA, as well as for detecting perioperative emboli, postoperative thrombosis, and postoperative hyperperfusion. – It still remains unclear at what FV shunt placement is indicated. – Emboli occurring during dissection and wound closure are particulate and are more important in predicting adverse events than predominantly gaseous emboli that occur during shunt placement and cross-clamp release. – Occurrence of particulate emboli may be amenable to changes in surgical technique such as back bleeding, flushing, and the use of Dextran-40. – Postoperative hyperperfusion is seen in ∼1% of patients and may present with headache, facial and eye pain, neurologic deficit, and seizures. FV may be up to 230% above baseline and could potentially be used to guide hemodynamic management. – TCD has not yet been shown to improve outcome in CEA patients. • Cardiac surgery – Loss of cerebral autoregulation and occurrence of emboli may be seen during cardiopulmonary bypass. – TCD may be useful in guiding perfusion pressure management, but data has not demonstrated an improvement in outcome. – There is some evidence to support the use of TCD during surgical repair of type A aortic dissection with retrograde cerebral perfusion.

EQUATIONS

• Doppler shift = 2 × Vf × Fsrc × cos(α)/V; where Vf is the velocity of blood flow, Fsrc is the

transmitted frequency source, V is the speed of sound in soft tissue (constant value 1540 m/s), and a is the angle of insonation. • PI = (PSV – EDV)/MV • RI = (PSV – EDV)/PV

REFERENCES

1. Doblar D.Intraoperative transcranial ultrasonic monitoring for cardiac and vascular surgery. Semin Cardiothorac Vasc Anesth. 2004;8:127–145. 2. Fodale V, et al.Transcranial Doppler and anesthetics. Acta Anesthesiol Scand. 2007;51:839– 847. 3. Kincaid MS.Transcranial Doppler ultrasonography: A diagnostic tool of increasing utility. Curr Opin Anesthesiol. 2008;21:552–559. 4. Markus HS, et al.Asymptomatic embolisation for prediction of stroke in the Asymptomatic Carotid Emboli Study (ACES): A prospective observational study. Lancet Neurol. 2010;9:663–671. 5. Moppett IK, Mahajan RP. Transcranial Doppler ultrasonography in anaesthesia and

intensive care. Br J Anaesth. 2004;93:710–724. 6. Rigamonti A, et al.Transcranial Doppler monitoring in subarachnoid hemorrhage: A critical tool in critical care. Can J Anesth. 2008;55:112–123. 7. Tsivgoulis G, Alexandrov AV, Sloan MA. Advances in transcranial Doppler ultrasonography. Curr Neurol Neurosci Rep. 2009;9:46–54.

8. White H, Venkatesh B. Applications of transcranial Doppler in the ICU: A review. Intensive Care Med. 2006;32:981–994. 9. Saqqur M, Zygun D, Demchuk A. Transcranial doppler in neurocritical care. Crit Care Med.2007;35(5 Suppl):S162–S172. See Also (Topic, Algorithm, Electronic Media Element) • Cerebral vasospasm • Sickle cell disease • Rh factor • Carotid endarterectomy • Transient ischemic attack • Cardiopulmonary bypass

CLINICAL PEARLS

• Limitations – 8% of the population do not have acoustic windows and results – Results can be highly operator dependent. • Newer technology uses power motion mode (M-mode) to improve window detection and provides multigating and measurement of flow from multiple vessels to simplify operator dependence. • Newer multifrequency TCD technology (2.0 and 2.5 MHz simultaneously) allows for distinction between gaseous and solid emboli. • As vessel caliber narrows, FV will increase until a point when a rapid decrease occurs due to complete occlusion.

TRANSDUCERS

Aditya Venkataraman, MD Daniel R.C. Nieva, MD

BASICS DESCRIPTION

• Transducers are devices that convert one type of energy to another. • In the perioperative setting, transducers are utilized as invasive monitors that convert pressure waveforms into an electrical signal that is then displayed onto a monitor. The most commonly used monitors are intra-arterial, central venous, pulmonary artery, and intracranial catheters. PHYSIOLOGY PRINCIPLES

• Modern transducers are small, external, disposable chips with a fluid–air interface and sample frequencies >200 Hz. • Continuous fluid column. Changes in pressure or pulsatile fluctuations distal to the catheter are transmitted to the transducer via a continuous fluid column. – The catheter is inserted into the patient’s body at the desired location. – The fluid column goes from the catheter → stiff tubing → stopcock → stiff tubing → transducer → soft tubing → fluid bag (usually contains heparin).

FIGURE 1. Diagram of a generic 2-gas anesthesia machine.

• Transducer. Within the transducer is an internal diaphragm with a “strain gauge.” Pressure fluctuations from the fluid column are conveyed from the diaphragm to a silicon chip or simple wire; this movement or stretch results in voltage output by the strain gauge that is proportional to the pressure applied at the diaphragm. Consequently, pressure fluctuations result in changes in the electrical resistance of the strain gauge (V = IR; where V is voltage, I is current, and R is resistance). • Wheatstone bridge component. Describes the circuitry of the transducer chip. The unknown resistance at the strain gauge (from pressure fluctuations) can be deduced using the three known resistance values of the bridge component; application of Kirchhoff’s law states that the algebraic sum of all voltages and currents in a loop must equal zero. The Wheatstone bridge is capable of measuring small changes in resistance and, therefore, is also suitable to

measure the resistance change in a strain gauge.

FIGURE 2. Wheatstone bridge component. R1, R2, and R3 voltages are known and Rx can be calculated because the

algebraic sum of all voltages should equal zero.

• Electronic data. Changes in resistance are subsequently converted to electronic data (e.g., systolic, diastolic, and mean arterial pressures). • Fourier analysis. Arterial, central venous, and pulmonary artery pressure tracings are complex waveforms best translated using Fourier analysis. This method allows the arterial waveform to be expressed as a summation of simple sine and cosine waves. The quality of the transduced waveform varies with the characteristics of the intravascular catheter, connection tubing, and the actual transducer system. • Frequencies. The frequency of the transducer must exceed the frequency of the arterial or (venous) waveform. Most commercially available transducers have frequencies >200 Hz. If the transducing system has a frequency that is too low, frequencies of the measured waveform will approach the frequency of the transducer. Consequently, the system will resonate and pressure waveforms recorded on the monitor will be amplified versions of true arterial pressure. • Damping describes a decrease in frequency through the continuous fluid column. The waveform is “smoothed" out and the dicrotic notch is often flattened or absent. This results in underestimating the systolic pressure and overestimating the diastolic pressure. The mean arterial pressure remains accurate. Examples of this include – Air bubbles – Long, narrow, and compliant tubing – Presence of additional stopcocks – Loose connections – Kinks in the catheter or tubing – Blood in the transducer – Clots in the catheter – Empty flush bag – Low cardiac output (cardiogenic shock, sepsis, severe hypovolemia)

• Underdamping describes excessive resonance in the system; the tracing is characterized by a high initial spike in the waveform. This results in overestimation of systolic pressure and an underestimation of diastolic pressure. The mean arterial pressure remains accurate. Examples include – Long, excessive tubing – Excessive catheter movement (catheter whip/fling) – Atherosclerosis – Vasoconstriction – Aortic regurgitation – Hyperdynamic states – Hypertension – Catheter occlusion of the vessel

• Flush bags preserve the accuracy of readings by preserving the integrity of the transducer. They are usually pumped up to 300 mm of pressure and control the forward flow of flush into the system, keeping it open, at a rate of ∼3–4 mL/hour. Otherwise, the pressurized fluid from the patient would climb back up the catheter. Heparin is sometimes added to avoid clotting; however, it appears that the pressure itself is sufficient. Additionally, heparin should not be used in patients with heparin-induced thrombocytopenia. PERIOPERATIVE RELEVANCE

• The accuracy of the transducer is heavily dependent on correct calibration and zeroing. Depending on the desired level of zeroing (mid-axillary line for arterial catheters), a stopcock at the level of the desired point of measurement is opened to air (atmosphere) and the system zeroed. • For procedures in the sitting or beach chair position, the arterial pressure in the brain differs from that at the level of the heart. Thus, the transducer should be zeroed at the level of cerebral circulation, most often the external auditory meatus (approximates the level of the Circle of Willis). • The transducer must be moved in tandem with patient movement. If the transducer falls below the point of zeroing, transduced pressures will be falsely elevated. Conversely, if the

transducer is raised above the point of zeroing, transduced pressures will be falsely decreased. • Raising or lowering the transducer relative to the patient will alter the reading. A 10 cm change in height will alter the arterial line pressure reading by 7.5 mm Hg. The same change would occur for CVP since in both systems, the transducer interprets a change in fluid column level as a change in pressure (1 mm Hg = 1.36 cm H2O). • Flush test. Performing a high-pressure flush and observing the initial oscillations prior to return of the pressure waveform can aid with identifying damping and underdamping within the system. Overdamping is indicated by a gradual pressure decay or an undershot and slow return to baseline without any oscillation after a flush. In contrast, underdamping is revealed by widely spaced oscillations.

REFERENCE

1. Estafanous FG, Barash PG, Reves JG. Cardiac Anesthesia: Principles and Clinical Practice. Philadelphia, PA: Lippincott; 2001:198. 2. Feinstein DM, Raemer DB. Arterial-line monitoring system simulation. J Clin Monit Comput. 2000;16(7):547–552. 3. Joshi AW, Raybagkar VH, Desa VV, et al. Emerging Physics. India: Pearson Education; 2010:81. 4. McCann UG II, Schiller HJ, Carney DE, et al. Invasive arterial BP monitoring in trauma and critical care: Effect of variable transducer level, catheter access, and patient position. Chest. 2001;120(4):1322–1326. 5. Saidman LS, Smith WT. Monitoring in Anesthesia. MA: Waltham, Butterworth; 1985:89. 6. Sinclair I. Sensors and Transducer. MA: Waltham, Butterworth-Heinemann; 2001:88.

7. WM Mushin, PL Jones. Physics for the Anesthetist, 4th edn. NJ: Hoboken, Blackwell Scientific Publications; 1987:496–500. See Also (Topic, Algorithm, Electronic Media Element) • Blood pressure • Arterial line waveform • Pulmonary artery catheter waveforms • Systole • Diastole

CLINICAL PEARLS

• The natural frequency of the transducer system is optimized by: – Minimizing tubing length – Minimizing the number of air bubbles within the tubing – Using a low-complicance/high-pressure tubing

TRANSFUSION INFECTIONS Anh-Thuy Nguyen, MD

BASICS DESCRIPTION

• Improvements in public health have reduced the risk of transfusion infection. Today, the risk of transfusion infections is much less than that of transfusion reactions. • Bacterial infection remains the most frequent infectious complication, while viral and parasitic infections are also possible. Additionally, a more mobile donor population has increased the variety of infections found in the blood supply. EPIDEMIOLOGY Prevalence

• The incidence and prevalence of the disease below are not the same in the blood donor population as that in the general public. The number changes again once the donors and blood units are screened. Hence, the transfusion risk is often cited. • Viral infections – Cytomegalovirus (CMV): 50–70% of adults are carriers (1) – Enterovirus – Epstein–Barr virus (EBV): 90% of adults are carriers – Hepatitis A virus (HAV): Donor screening only; hepatitis B virus (HBV): 1/500,000 per unit exposure (PUE); hepatitis C virus (HCV): 1/2,000,000 PUE – HIV: 1/2,000,000 PUE – Human parvovirus B19: 50–60% of adults by the age of 30 years are seropositive, and 90% of those older than 60 years – Human T-cell lymphotropic virus-1 (HTLV-1): <1/650,000 PUE; HTLV-2: <1/650,000 PUE – West Nile virus (WNV) (Flaviviridae): 2.2–10/10,000 PUE in endemic area • Bacterial infections: Most frequent – Platelets are stored at room temperature and have the highest incidence: 1/100,000 PUE with a fatality rate of 1/500,000 PUE. Risk is further increased with pooled random-donor compared to single-donor apheresis platelets. – Red blood cells: 1/5,000,000 PUE, fatality rate of 1/8,000,000 PUE • Parasitic infections – Babesiosis (Babesia spp.): Over 70 cases from 1979 to 2008, 12 were fatal. – Chagas disease (Trypanosoma cruzi): A few cases reported. – Malaria (Plasmodium spp.): <1/1,000,000 PUE (greater in endemic areas), 11% fatality • Other – Variant Creutzfeldt–Jakob disease (vCJD): A few cases reported (5) • Emerging infectious disease threats – Severe acute respiratory syndrome (SARS), Monkey Pox, Leishmania, Influenza, Dengue

Fever, Chikungunya virus (CHIKV), Xenotropic murine leukemia virus (XMRV)

ETIOLOGY/RISK FACTORS

• Donor population • Technique of blood collection • Storage conditions

PHYSIOLOGY/PATHOPHYSIOLOGY

• CMV. Usually asymptomatic; those who develop symptoms may experience an illness resembling infectious mononucleosis (fever, swollen glands, fatigue). In compromised immune systems, serious illness involving fever, pneumonia, liver infection, anemia, and retinitis. Symptomatic babies can develop nervous system damage and developmental disabilities. • Enterovirus. 66 human enterovirus serotypes have been identified (e.g., polioviruses, Coxsackie A viruses, Coxsackie B viruses, and echoviruses). Symptoms can range from mild respiratory illness (common cold), GI infection, “hand, foot and mouth” disease, pleurodynia, acute hemorrhagic conjunctivitis, herpangina, aseptic meningitis, myocarditis, severe neonatal sepsis-like disease, to acute flaccid paralysis. • EBV (herpes virus HHV-4). Can cause infectious mononucleosis 35–50% of the time. It increases the risk of developing Burkitt’s lymphoma, nasopharyngeal carcinoma, and B-cell lymphoma in the immunocompromised patients. • Hepatitis A is self-limited and without chronic manifestations; not tested by the blood bank. • Hepatitis B is an acute infection that can cause fulminant hepatitis. 6–10% of infected patients become chronic carriers. Chronic HBV infection can lead to cirrhosis and hepatocellular carcinoma. • Hepatitis C. 80% of infected people are asymptomatic. Acute infection can cause flu-like symptoms, jaundice, abdominal pain, fatigue, and decreased appetite. Chronic infections can lead to cirrhosis and hepatocellular carcinoma. • HIV. Many infected people may show little or no symptoms until years later. Within the first few weeks of infection, one may have flu-like symptoms. Years later, lymphadenopathy, diarrhea, weight loss, fever, cough, shortness of breath, and progression to AIDS can result. In addition, they may experience soaking night sweats, chills, fever >38°C for several weeks, persistent lesions in the mouth, headaches, blurred vision, and skin lesions. • Human parvovirus B19 causes mild symptoms in healthy patients (slapped cheeks in children, limited arthritis, cold-like symptoms in adults). Parvovirus can cause aplastic anemia in AIDS patients, aplastic crisis in patients with sickle cell anemia and hereditary spherocytosis, and hydrops fetalis due to severe fetal anemia resulting in miscarriage or stillbirth in pregnant women. • HTLV is associated with the development of acute T-cell leukemia/lymphoma. • WNV. 80% of infected people are asymptomatic. Of those who show symptoms, most have flu-like symptoms. 1 in 150 will develop severe illness ranging from high fever and neck stiffness to stupor, disorientation, coma, tremors, convulsions, and paralysis. Symptoms may last for weeks, and neurological effects may be permanent. • Bacteremia signs and symptoms can include high fever, high white cell count (if the patient is not neutropenic), tachypnea, tachycardia, hypotension, to GI symptoms such as nausea,

vomiting or abdominal pain. Escherichia coli: Diarrhea, usually bloody, and can lead to kidney failure. Klebsiella oxytoca: Pneumonia, diarrhea. Klebsiella pneumonia: Pneumonia, empyema. Pseudomonas aeruginosa: Endocarditis, meningitis, brain abscess, osteomyelitis, malignant otitis externa, characteristic skin lesions called ecthyma gangrenosum. Serratia marcescens: Pneumonia, meningitis, and cerebral abscess, osteomyelitis, skin ulcers. Staphylococcus aureus: Endocarditis, pneumonia. Staphylococcus lugdunensis: Endocarditis. – Syphilis (Treponema pallidum): 4 stages of syphilis with different presentations. Stage 1 or primary syphilis – skin lesion (chancre); stage 2 or secondary syphilis – rash on palms of hands and bottoms of feet and mucus lesions, sometimes accompanied by lymphadenopathy; Stage 3 or latent syphilis – asymptomatic but can infect others; Stage 4 or tertiary syphilis – can affect multiple organs with gummata, cardiovascular syphilis, neurosyphilis. – Yersinia spp.: Abscess in liver, kidney, spleen, lungs, cellulitis, pyomyositis, pneumonia, meningitis, panophthalmitis, endocarditis, osteomyelitis, infected mycotic aneurysm • Parasitic infections – Babesiosis: Tick-borne malaria-like illness caused by species of the intraerythrocytic protozoan Babesia. Symptoms include fever, hemolytic anemia, and hemoglobinuria. – Chagas disease: Acute stage symptoms can include flu-like symptoms, myocarditis, and mengoencephalitis. Chronic disease affects the nervous system (encephalopathy, dementia, motor deficits), digestive system (megacolon and megaesophagus), and heart (cardiomyopathy). – Malaria: Ranging from flu-like symptoms to anemia, jaundice, convulsion, and coma. • Other. vCJD is a rapidly progressive dementia accompanied by physical and speech impairment as well as seizures.

PREVENTATIVE MEASURES

• The Abbreviated Donor History Questionnaire (ADHQ) focuses on querying donors about factors that best predict recent infection. – Today: “Are you feeling well and healthy today?” – In the past 12 months have you: “Had a blood transfusion?” “Had a transplant such as organ, tissue, or bone marrow?” “Had a graft such as bone or skin?” “Come into contact with someone else’s blood?” “Had an accidental needle-stick?” “Had sexual contact with anyone who has HIV/AIDS or has had a positive test for the HIV/AIDS virus?” “Had sexual contact with a prostitute or anyone else who takes money or drugs or other payment for sex?” “Had sexual contact with anyone who has ever used needles to take drugs or steroids, or anything not prescribed by their doctor?” “Had sexual contact with anyone who has hemophilia or has used clotting factor concentrates?” “Had sexual contact with a person who has hepatitis?” “Had a tattoo?” “Had ear or body piercing?” “Had or been treated for syphilis or gonorrhea?” “Been in juvenile detention, lockup, jail, or prison for more than 72 hours?” Female donors: “Had sexual contact with a male who has ever had sexual contact with another male?” – In the past three years have you: “Been outside the United States or Canada?” – From 1980 to the present, did you: “Spend time that adds up to five years or more in Europe?” “Receive a blood transfusion in the United Kingdom?” – From 1977 to the present, have you: “Received money, drugs, or other payments for sex?”

Male donors: “Had sexual contact with another male, even once?” – Have you ever: “Had a positive test for the HIV/AIDS virus?” “Used needles to take drugs, steroids, or anything not prescribed by your doctor?” “Used clotting factor concentrates?” “Had hepatitis?” “Had malaria?” “Had Chagas’ disease?” “Had babesiosis?” “Received a dura mater (or brain covering) graft?” “Had sexual contact with anyone who was born in or lived in Africa?” “Been in Africa?” “Have any of your relatives had Creutzfeldt-Jakob disease?” • Proper collection technique at donation involves sterilizing the donor’s skin prior to phlebotomy and diverting the first 10–30 cc of blood collected into an integral pouch separate from the collection bag. • Cold storage inhibits infectious growth; syphilis disappears • Preferential use of apheresis platelets reduces donor exposure • Leukoreduction of donor units is indicated in immunocompromised and immunologically naïve patients for CMV (reduces the risk of infection), enterovirus (risk of infection negligible), EBV, Chagas disease. • Pathogen reduction methods or pathogen inactivation/reduction technologies (PRTs) (6) involves the use of heat treatment, solvent/detergent (S/D) treatment, and filtration methods for fractionated plasma-derived therapeutics. Other methods used in Europe but not yet adopted in the US include methylene blue treated FFP, use of the helix/intercept system or intercept platelet system (which prevents DNA replication), and use of riboflavin and light treatment for platelets • Use of viral and bacterial detection methods (NATs, serology tests, and antibody binding) – CMV: Particle agglutination and enzyme-linked immunosorbent assay (ELISA) test – Viral screening of blood units: NAT (nucleic acid testing or nucleic acid amplification technique) HBV DNA NAT, HCV RNA NAT, HIV RNA NAT, WNV NAT – HTLVl/ll: Antil-HTLVI and anti-HTLVll – Syphilis: Treponemal test – T. cruzi antibody screening

PREOPERATIVE ASSESSMENT • Maintain a high index of suspicion for post-transfusion infection • Test for suspected organism in the recipient for bacteria, mycobacteria, fungus, virus, parasite, etc. • Investigate when unexplained clinical events occur after transfusion that are consistent with transfusion-transmitted infection, such as encephalitis, meningitis, or other unexplained CNS abnormalities, sepsis, hemolytic anemia and/or fever (in cases of babesiosis or malaria), death. • For pathogens routinely screened in the blood donor, test for any infection in the recipient occurring within 6 months after transfusion if (a) The index donation testing was negative but (b) The donor was subsequently found to be infected, and (c) The recipient had no pretransfusion history of the same infection.

DIFFERENTIAL DIAGNOSIS • Blood transfusion reaction

• Infection from other sources

TREATMENT • Stop transfusion if fever or tachycardia occurs during a transfusion, or discolored blood bag • Culture patient and product bag • Use supportive measures (such as antibiotics, antiviral, vasopressors, and fluids as needed) • Treat each infection accordingly.

REFERENCES

1. Pamphilon DH, Rider JR, Barbara JA, et al. Prevention of transfusion-transmitted cytomegalovirus infection. Transfus Med. 1999;9:115–123. 2. Perkins HA, Busch MP. Transfusion-associated infections: 50 years of relentless challenges and remarkable progress. Transfusion. 2010;50:2080–2099. 3. Kuehnert MJ, Roth VR, et al. Transfusion- transmitted bacterial infection in the United States, 1998–2000. 4. Transfusion. 2001;41:1493–1499. 5. CDC.gov 6. Hewitt PE, Llewelyn CA, et al. Creutzfeldt-Jacob disease and blood transfusion: Results of the UK transfusion medicine epidemiological review study. Vox Sang. 2006;91:221–230. 7. Goodrich RP, Custer B, Keil S, et al. Defining “adequate” pathogen reduction performance for transfused blood components. Transfusion. 2010;50:1827–1837.

ADDITIONAL READING

• The National Healthcare Safety Network Manual—NHSN Biovigilance Component Protocol (www.cdc.gov/nhsn/PDFs/hemovigModuleProtocol_current.pdf) • www.FDA.gov Simplified Blood Donor Screening Questions

See Also (Topic, Algorithm, Electronic Media Element) • Infectious disease in healthcare workers • Platelets • Transfusion-related lung injury (TRALI) • Postoperative jaundice • Hepatitis C

CODES ICD9 999.34 Acute infection following transfusion, infusion, or injection of blood and blood products

ICD10

T80.22XA Acute infct fol tranfs,infusn,inject blood/products, init

CLINICAL PEARLS

• Despite improved screening techniques, infectious disease remains a real consequence of product transfusion.

TRANSFUSION-RELATED ACUTE LUNG INJURY (TRALI) Marc A. Logarta, MD, DABA, FANZCA

BASICS DESCRIPTION

• Transfusion-related acute lung injury (TRALI) is a complication of allogenic blood transfusion. Today, it is the number one cause of transfusion-related morbidity and mortality and exceeds that of infectious disease transmission. • Recent clinical and radiological parameters have been formulated to aid with the diagnosis: – TRALI has an acute onset, hypoxemia (PaO2/FiO2 <300, SpO2 <90% on room air, or other clinical evidence of hypoxia), bilateral infiltrates on CXR, and no evidence of left atrial hypertension. – There should be no preexisting ALI prior to transfusion. – During, or within 6 hours of, transfusion – No temporal relationship to an alternative risk factor for ALI. • Characteristics of TRALI are indistinguishable from noncardiogenic pulmonary edema or ALI due to other etiologies. EPIDEMIOLOGY Prevalence

• May be underestimated due to diagnostic ambiguity, rapid progression, and its rare occurrence. Diagnostic criteria have only been recently proposed and accepted. • Packed red blood cells: 1:4,000–1:557,000 transfused units • Fresh frozen plasma (FFP): 1:7,800–1:74,000 transfused units • ICU population: 8% (recent prospective cohort study with current diagnostic guidelines)

Morbidity

• Increased oxygen support is required in100% of patients • Mechanical ventilation is required in 75% of patients.

Mortality

• Ranges from 6% to 20%. • In 2006, there were 35 reported deaths in the US (greater than all other causes of transfusion-related mortality combined). • Remains significantly less than other forms of ALI (which range from 40% to 60%). However, it should be noted that transfusion of blood products is an independent risk factor for the development of (other forms of) ALI (and hence mortality). ETIOLOGY/RISK FACTORS

• All donor blood components: Whole blood, packed red blood cells, apheresed platelets, whole blood platelets, FFP, cryoprecipitate, granulocytes, IV immunoglobulin, and stemcell

products (greater when products with high volumes of plasma are given). • Plasma from multiparous donors has high levels of antibodies to human leukocyte antigen (HLA) and human neutrophil alloantigen (HNA). Antibodies to HLA and HNA develop through exposure to fetal blood and can be present in up to 25% of units. • Donors who have been previously implicated in TRALI; up to 65%. • Recipients who have had multiple transfusions • Recipients of organ transplantation • Critically ill recipients; “first hit.”

PHYSIOLOGY/PATHOPHYSIOLOGY

• The pathophysiology is not completely understood. Current evidence suggests that there are two mechanisms at play: Immune antibody-mediated and non-immune. • Immune mediated (antibody-mediated TRALI). Donor leukoagglutinating (HLA Class I, HLA Class II, neutrophil-specific) antibodies bind to and activate recipient neutrophils. These neutrophils collect (or get trapped) in the pulmonary capillary beds. In approximately 6% of TRALI cases, donor neutrophils bind to recipient leukoagglutinating antibodies, resulting in activated neutrophils that can also collect in the pulmonary capillary beds. • Nonimmune mediated (“two-hit phenomenon”). The first hit involves immune priming and is on a continuum with activation and injury. Critically ill patients may be prone to pulmonary vascular endothelial insult from sepsis, cancer, recent surgery, cytokine administration, massive transfusion, cardiac disease, or trauma. The second hit involves the introduction of a TRALI-inducing agent. When donor plasma is transfused, biologically active lipids, antibodies, cytokines, or endotoxins, that have been accumulated during storage, are more likely to activate recipient neutrophils that collect (or get trapped) in the pulmonary capillary beds. • In BOTH immune and nonimmune TRALI, the activated neutrophils collect and sequester in the pulmonary capillary beds, release inflammatory mediators (IL-1, IL-6, TNF, IL-18), granules, oxygen radicals, and proteases as well as set-off a complement cascade. Ultimately, both pathways result in endothelial damage, protein leak, and pulmonary edema. • Pathological findings – Interstitial and intra-alveolar edema with proteinaceous fluid – Neutrophil extravasation into the interstitium and alveolar airspaces, as well as increased numbers within the pulmonary capillary vasculature – Destruction of pulmonary vasculature • Clinical manifestations – Result from increased vascular permeability to fluid and protein into interstitial and intraalveolar spaces (hallmark of noncardiogenic pulmonary edema; whereas cardiogenic pulmonary edema results from increased hydrostatic pressure). – Alveolar atelectasis causes V/Q mismatching and hypoxia. – Signs/symptoms, laboratory findings, and imaging mimic acute respiratory distress syndrome (ARDS).

PREVENTATIVE MEASURES

• Increased clinician awareness has resulted in increased vigilance regarding this disease

entity • Sourcing plasma from male donors (95% of plasma from American Red Cross is from males) • Use of “fresher" platelets and red cells – which may have reduced lipid priming activity • Screening of parous female donors for HLA Ab and antineutrophil Ab would identify donors that may pose a risk. • Identifying cases of TRALI so that other units from the same donor can be identified. Testing of the donor in question and if positive, deferring them from future donations. • Use of pooled solvent/detergent treated plasma (Europe).

PREOPERATIVE ASSESSMENT • Physical exam – Vital signs reveal tachypnea, hypoxia, tachycardia, hypotension, and fever – General: Shortness of breath – Respiratory: Need for high FiO2 to maintain oxygen saturation, diffuse bilateral rales,

cyanosis of lips and nail beds – Cardiac: Rule out cardiac pulmonary edema including jugular venous distension or S3 gallop • Monitors – EKG: Rule out the possibility of cardiac pulmonary edema including ST segment changes, T-wave inversions, arrhythmias – Invasive arterial line: Frequent arterial blood gas monitoring – Pulmonary capillary wedge pressure: Should show normal left-sided filling pressures • Diagnostic procedures – Chest radiography: Bilateral pulmonary infiltrates (may persist despite symptom improvement) – Arterial blood gases: PaO2/FiO2 <300

– Transesophageal echocardiogram: Aids with the exclusion of other diagnoses (e.g., cardiogenic pulmonary edema) – Antigen and antibody testing: Donor samples can be obtained from all remaining product given in the past 6 hours or a fresh sample from the donor. They should be tested for HLA Class 1, HLA Class 2, and neutrophil-specific antibodies. – Leukocyte crossmatch between donor serum and recipient leukocytes; if positive, confirms the diagnosis of immune TRALI.

DIFFERENTIAL DIAGNOSIS

• Transfusion-associated circulatory overload (TACO) • Noncardiogenic pulmonary edema; ARDS from aspiration, pneumonia, lung contusion, shock, trauma, sepsis. May be clinically indistinguishable. • Cardiogenic edema • Allergic and anaphylactoid reactions • Bacterial contamination of transfused blood products (sepsis) • Acute hemolytic transfusion reaction

TREATMENT • Stop transfusion. • Oxygen support for mild cases but often intubation and mechanical ventilation is required. • If ventilatory support is required, a ventilatory strategy that would avoid further lung injury is reasonable. As with treatment of other patients with ALI, avoidance of high peak inspiratory pressures is recommended. • Notify the blood bank and return the remaining product for testing. • Consider fluid administration if clinically hypovolemic. Unlike cardiac pulmonary edema or ARDS, diuretics are not indicated. • Steroids are controversial; at this time, there is no convincing evidence that demonstrates an improved outcome. • Hemodynamic support may be necessary. • In contrast to other etiologies of ALI, the recovery from immune-mediated TRALI is relatively better. Most cases will resolve in 1–5 days.

FOLLOW-UP After transfusion is stopped, the hypoxemia usually resolves in the following 48–96 hours.

REFERENCES

1. Bux J.Transfusion-related acute lung injury (TRALI): A serious adverse event of blood transfusion. Vox Sanguinis. 2005;89:1–10. 2. Bux J. The pathogenesis of transfusion-related lung injury (TRALI). Br J Haematol. 2007;136(6):788–799. 3. Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusion-related acute lung injury: Statement of a consensus panel. Transfusion. 2004;44:1774–1789. 4. Triulzi D. Transfusion-related acute lung injury: Current concepts for the clinician. Anes Analg. 2009;108(3):770–776. See Also (Topic, Algorithm, Electronic Media Element) • Hypoxia • Noncardiogenic pulmonary edema • Adult respiratory distress syndrome

CODES ICD9 518.7 Transfusion related acute lung injury (TRALI) ICD10 J95.84 Transfusion-related acute lung injury (TRALI)

CLINICAL PEARLS

• Leading cause of transfusion-related morbidity and mortality in the US. • Previously a diagnosis of exclusion; however, more defined criteria have been recently established. • Treatment should consist of early diagnosis and support with oxygenation. Other causes of acute respiratory distress and ALI should also be considered as their treatment is very different.

TRANSIENT ISCHEMIC ATTACK Tod A. Brown, MD

BASICS DESCRIPTION

• Transient ischemic attacks (TIAs) are a sudden, temporary, stroke-like condition of presumed vascular origin. The traditional or historical definition describes it as, “cerebral dysfunction of ischemic nature lasting no longer than 24 hours with a tendency to recur.” • A modified, tissue-based definition implements neuroimaging findings and describes TIAs as, “a brief episode of neurological dysfunction caused by focal brain or retinal ischemia, with clinical symptoms lasting less than an hour and without neuroimaging evidence of acute infarction.” • Patients with a history of TIAs may present for urgent or emergent carotid endarterectomy, craniotomy, or minimally invasive interventional procedures. Additionally, patients may present for surgery unrelated to the disease or have postoperative manifestations of TIAs. EPIDEMIOLOGY Prevalence

In the US: 200,000–500,000/year Morbidity

• Ninety-day risk of stroke following a TIA: 10–20% • Five-year risk of stroke following a TIA: 30%

Mortality

• Combined 10-year risk of stroke, MI, or vascular death of 42.8% (~4% per year). • Stroke is the second most common cause of death worldwide (1).

ETIOLOGY/RISK FACTORS

Risk factors for experiencing a TIA include • Hypertension; most prevalent and significant (2) • Cigarette smoking • Obesity • Hyperlipidemia • Heart disease • Carotid artery disease • Diabetes • Alcoholism • Atherosclerosis • Polycythemia • Sickle cell anemia

PHYSIOLOGY/PATHOPHYSIOLOGY

• TIA may be considered an ischemic penumbra of varied duration; it can proceed to cerebral infarction or resolve, but must be considered a harbinger of stroke. • It is the result of temporary hypoperfusion secondary to various causes. The most common cause is an embolus that frequently arises from distant sites like the aorta, cardiac clots (atrial fibrillation), or bifurcation of the internal carotid, middle, or anterior cerebral arteries. They are typically comprised of platelet-fibrin or atherosclerotic material.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patients on anticoagulation who are presenting for surgery unrelated to their TIAs should be discussed with the surgeon, neurologist, cardiologist, or primary care physician regarding ideal management. Consider bridging therapy prior to the surgery with low molecular weight heparin and reinstituting therapy as soon as possible. • Patients who present postoperatively with TIAs should be evaluated expeditiously with appropriate neurological evaluation, so that intervention such as anticoagulation or invasive radiological therapy has the chance to interrupt or limit progression to stroke.

PREOPERATIVE ASSESSMENT SYMPTOMS

Syncope, loss of balance, vision changes, weakness or heaviness in extremities, numbness especially in the face, arms or legs, change in speech pattern or recognition. History

• Brief episode(s) of stroke-type symptoms with rapid resolution and complete recovery. • Risk factors, including atrial fibrillation, cardiac shunts and lesions such as artificial valves, may be completely or partially evaluated. • Patients may have coincident decreases in level of cognition, orientation, and neurological function, which should be noted to facilitate postoperative evaluation.

Signs/Physical Exam

• Because TIA is defined as the resolution of stroke type symptoms, the physical exam is often benign. However, neurological deficits should be determined and documented appropriately. • Carotid bruits, irregularly irregular rhythm, or cardiac murmurs.

TREATMENT HISTORY

• Corrective procedures: Carotid endarterectomy, intracranial–extracranial bypass, or invasive radiological procedures (stenting). • Electrophysiologic ablation procedures

MEDICATIONS

• “Blood thinners:” Aspirin, clopidogrel, heparin • Statins (for their pleiotropic, membrane stabilizing properties)

• Antidysrhythmics

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC • Electrolytes, BUN, Cr, glucose • Evaluation of hypercoagulability • EKG; cardiac rhythm disturbances, such as atrial fibrillation, should be completely evaluated and treated. • Echocardiogram to evaluate chamber size, clots, and shunts (PFO). • Carotid Doppler studies • C-reactive protein is of interest and may be helpful to predict future stroke and TIA, but may not be useful as an immediate preoperative test (3). • MRI/CT

CONCOMITANT ORGAN DYSFUNCTION

• Vascular disease (coronary artery and renal disease) • Diabetes can complicate large vessel occlusive disease with small vessel disease; worsening perfusion problems. • Hypertension makes the risk of end-organ ischemia under anesthesia, secondary to relative hypotension, a concern. • Arrhythmias

CIRCUMSTANCES TO DELAY/CONDITIONS

• Partially or improperly evaluated TIAs need proper investigation prior to elective surgery. • Recent or accelerating episodes of TIA. • Uncontrolled hypertension. SBP >200 mm Hg and DBP <100 mm Hg are reasons to consider delay. • Potassium and electrolytes should be optimized to reduce the incidence of rhythm disturbance in patients with a history of, or strong risk factors for TIAs or stroke. CLASSIFICATIONS

• ABCD2 classification for TIA helps to define risk (higher scores are associated with increased risk of stroke) and guide treatment. – A: Age over 60 years is 1 point – B: BP >140/90 mm Hg is 1 point – C: Clinical features, including unilateral weakness, are 2 points and speech disturbance without weakness is 1 point. – D2: Diabetes is 1 point and duration of symptoms 1 point for <60 minutes and 2 points for >60 minutes (4). • CHADS2 scoring aids with assessing the risk of stroke in patients with atrial fibrillation. – CHF, hypertension, age over 75, diabetes, and stroke get one point for each of the risk factors. – Prior stroke or TIA receives 2 points. – A score of five or six, history of a stroke or TIA within 3 months, or rheumatic valvular

heart disease are at high risk (5).

TREATMENT PREOPERATIVE PREPARATION Premedications

• Continue scheduled antiarrhythmics and antihypertensives on schedule. • Perioperative beta-blockers have been associated with an increase in stroke, possibly due to hypotension. If utilized, they should be done cautiously while maintaining adequate cerebral perfusion pressures. INTRAOPERATIVE CARE Choice of Anesthesia

• Depends on the surgical procedure, comorbidities, and patient preference. • Neuraxial techniques may be contraindicated by anticoagulants.

Monitors

• Standard ASA monitors • Arterial line may be appropriate in patients with severe cerebrovascular disease to ensure adequate cerebral perfusion pressures or with cardiac arrhythmias (in concordance with the surgical procedure). • BIS monitoring may be helpful in detecting CNS ischemia/TIA (6). Induction/Airway Management

Induction agent choice should maintain stable hemodynamics (avoid hypotension, hypertension, sympathetic stimulation that can exacerbate arrhythmias). Maintenance

No specific anesthetic technique (volatile versus IV) has been shown to decrease the incidence of intraoperative cerebral ischemia, TIAs, or postoperative stroke. Extubation/Emergence

• Hypertension may require antihypertensives like labetalol, esmolol, or nitroglycerin. • Wakefulness post emergence aids the immediate neurological evaluation.

FOLLOW-UP BED ACUITY

Depends on the surgical procedure, patient comorbidities, and intraoperative events MEDICATIONS/LAB STUDIES/CONSULTS

• Delayed emergence can occasionally simulate postoperative TIA so a brief period (15 minutes) of observation may be warranted prior to further workup. Neurology consultation

and diagnostic studies such as CT scan or MRI scan as appropriate. • Reinstitution of “blood thinners” should be done as soon as safely possible. • Reinstitution of antihypertensives and stains should be performed as soon as possible.

COMPLICATIONS • Stroke • Confusion

REFERENCES

1. age BF, et al.Validation of clinical classification schemes for predicting stroke. JAMA.2001;285(22):2864–2870. 2. aston OJ, et al.Definition and evaluation of transient ischemic attack. Stroke. 2009;doi:1 0.1161/STROKEAHA.1 08.192218 (A). 3. i Napoli M, et al.Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke. Stroke. 2005;36(6):1316–1329 (B).

4. ora S, Ridker PM. Justification for use of statins in primary prevention. Am J Cardiol. 2006;97(2A):33A–41A. (B) 5. ohnston SC, et al.Validation and refinement of scores to predict very early stroke risk after TIA. Lancet. 2007;369:283–292. (B) 6. leeker CP, et al.Bispectral index changes during acute brainstem TIA/ischemia. Case Reports in Medicine. 2010; Article 697185. doi:10.1155/2010/697185 (C). 7. acco RL, Adams R, Albers G, et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: A statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: Cosponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline. Circulation. 2006;113:e409–449. (B) 8. ost N, et al.Plasma concentration of c-reactive protein and risk of ischemic stroke and transient ischemic attack. Stroke. 2001;32:2575. (A) 9. eenith TV, et al.Perioperative care of a patient with stroke. Int Archf Med. 2010;3:33 DOI:10.1186/1755-3-33. (B) 10. olf PA, Clagett GP, Easton JD, et al. Preventing ischemic stroke in patients with prior stroke and transient ischemic attack: A statement for healthcare professionals from the Stroke Council of the American Heart Association. Stroke. 1999;30:1991–1994. (A) See Also (Topic, Algorithm, Electronic Media Element) • Postoperative stroke • Carotid endarterectomy • Perioperative statins • Perioperative hypertension • Atrial fibrillation • Circle of Willis

• Sickle cell anemia • Cigarette smoking

CODES ICD9

• 435.8 Other specified transient cerebral ischemias • 435.9 Unspecified transient cerebral ischemia ICD10

• G45.8 Oth transient cerebral ischemic attacks and related synd • G45.9 Transient cerebral ischemic attack, unspecified

CLINICAL PEARLS

• Patients with a history of TIA have revealed to the practitioner that their anatomy and physiology is that of a “near miss” for stroke. Risk may be modified with preoperatively screening those with inordinate risk and changing the dynamics that predispose patients to CNS ischemia during the perioperative period. • TIA represents CNS ischemia and should be considered on par with cardiac ischemia: A precursor for infarction.

TRANSIENT NEUROLOGIC SYMPTOMS Sharon L. Lin, MD Jane C. Ahn, MD

BASICS DESCRIPTION

• Transient neurologic symptoms (TNS) present as lower back pain and lower extremity dysesthesias radiating to the buttock, thighs, and lower limbs after the resolution of a spinal anesthetic. • Symptoms vary from mild to severe and often resolve within 5 days. • The pathophysiology remains unclear; neurologic exams, MRI, and electrophysiologic testing have failed to demonstrate any abnormalities. • Although typically associated with intrathecal lidocaine, other local anesthetics including bupivacaine, tetracaine, and ropivacaine have also been shown to cause TNS. EPIDEMIOLOGY Prevalence

• Transient radicular irritation: 0.4% • TNS after spinal anesthesia: 10–37% • TNS risk is 6–7 times higher with lidocaine than with bupivacaine and five-fold higher than with prilocaine – Lidocaine 2% and 5% concentrations: Up to 33% occurrence – Bupivacaine 1–2% – Mepivacaine: 7% – Tetracaine: 1–3% – Procaine: 1% – Ropivacaine: 0–1% – Prilocaine: 0–1% Morbidity/Mortality

No reported long-term morbidity or mortality with TNS due to the transient nature of symptoms. Patient discomfort is the main adverse effect. ETIOLOGY/RISK FACTORS

• Etiology is not completely understood • Risk factors – Local anesthetics intrathecally (especially lidocaine) – Lithotomy position – Prolonged surgery – Vasoconstrictor additives to local anesthetic solutions, such as epinephrine – Outpatient status

– No association with glucose concentration, osmolarity of anesthetic solution and injected concentration of lidocaine – No association with age, height, weight, sex, needle type or size, difficulty of block placement, paresthesias

PHYSIOLOGY/PATHOPHYSIOLOGY

• Intrathecally administered local anesthetics induce a reversible block of neurotransmission at the spinal cord. • However, all local anesthetics also have the potential for neurotoxic or other adverse effects on the spinal cord, ranging from cauda equina syndrome to TNS. • TNS consist of self-limited lower back pain with radiation to the buttocks, thighs, and lower limbs after spinal blockade has resolved. Onset is typically within 12–36 hours of surgery with duration lasting 6 hours to 5 days. • The mechanism remains unclear and possibly results from local anesthetic neurotoxicity. The majority of data comes from retrospective studies and meta-analyses that help identify associated etiologies and describe the clinical course of symptoms. • Theories that have been proposed and discarded include spinal cord ischemia, extent of local anesthetic distribution, spinal infection, or hemorrhage. • TNS does not appear to be associated with neurologic pathology. TNS appears to be lacking identifiable pathology. Neurologic exams, radiographic imaging, electromyelography (EMG), and nerve conduction studies are usually normal. Specifically, there appears to be an absence of sensory-motor deficits, or muscle-tendon reflex abnormalities that are common with acute radicular irritation. • Local anesthetics – All local anesthetics have been reported to cause TNS – Intrathecal lidocaine is attractive for ambulatory surgery due to its intense sensory and motor blockade, combined with its short duration of action. Lidocaine, however, has been associated with up to a 30% incidence (even at concentrations as low as 0.5%). – Intrathecal mepivicaine also has a favorable pharmacokinetic profile in ambulatory surgery, but carries a reasonable incidence of TNS – Preservative-free 2-chloroprocaine has recently gained popularity for its excellent shortduration of spinal anesthesia with little risk for TNS. It should be noted, however, that in the 1980s, high-dose 2-chloroprocaine was associated with permanent neurological deficits that were believed to be due to the preservatives in the solution. • Position. The lithotomy position has been associated with a higher incidence of TNS. Possible causes include the stretching of the cauda equina and reduced perfusion pressure of the vasa nervorum. This combination may increase vulnerability of nerve fibers. • Outcome. TNS is characterized by its self-limited course. Greater than 90% of cases resolve completely within 1 week. This differs from other neurotoxic effects of local anesthetics such as cauda equina syndrome. – Cauda equina syndrome. Associated with permanent neurologic injury that is characterized by bowel and bladder dysfunction, pain and paresis of the lower extremities, and patchy sensory deficits. It has been associated with continuous spinal microcatheters, lidocaine 5% spinals, and 2-chloroprocaine (during the 1980s due to sodium metabisulfate formulations).

PREVENTATIVE MEASURES

• The avoidance of lidocaine in spinal anesthesia and the use of the lowest local anesthetic concentration that is available. If short duration is desired, consider preservative-free 2chloroprocaine. • Avoidance of vasoconstrictors in spinal anesthetic solution • Precautions to avoid stretch injury during lithotomy positioning or prolonged surgeries.

PREOPERATIVE ASSESSMENT • Symptoms, signs, physical exam – New onset low back pain after resolution of the sensory and motor blockade – Pain in buttocks radiating to the lower extremities. Thigh pain (especially the back of thighs) is greater than lower limb pain. Usually bilateral, but may be unilateral – Pain ranges from light to severe – Dysesthesia – Hypoesthesia – Aching – Hypesthesia – More commonly pain in thighs (especially back of thighs) rather than lower limbs • Diagnostic procedures and studies – Diagnosis of exclusion – Laboratory exam. Coagulation studies and white blood counts should be normal, which can assist in ruling out epidural hematoma and epidural abscess, respectively. – Consider CT scan or MRI to rule out other neurologic conditions. – No consistent abnormalities of nerve conduction velocity, EMG or SSEP in acute and delayed follow-up of TNS patients.

DIFFERENTIAL DIAGNOSIS

• Spinal hematoma • Epidural abscess • Permanent neurologic damage • Preexisting lower back pain

TREATMENT • NSAIDs • Opioids • Trigger point injections • Pain usually resolves after 2–5 days

FOLLOW-UP • Symptoms often disappear spontaneously by Day 5. • EMG, nerve conduction studies, or diagnostic imaging studies are usually not necessary.

• Consider neurology consultation if neurologic deficits persist beyond 10 days.

CLOSED CLAIMS DATA

No data, due to transient symptoms

REFERENCES

1. Freedman JM, Li DK, Drasner K, et al. Transient neurologic symptoms after spinal anesthesia. Anesthesiology. 1998;89:633–641.

2. Liu SS. Current issues in spinal anesthesia. Can J Anesth. 2002;49(6):R1–R5. Pollock J, Burkhead D, Neal JM, et al. Spinal nerve function in five volunteers experiencing transient neurologic symptoms after lidocaine subarachnoid anesthesia. Anesth Analg. 2000;90:658– 665. 3. Pollock JE, Neal JM, Stephenson CA, et al. Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anesthesia. Anesthesiology. 1996;84:1361– 1367.

4. Zaric D, Christiansen C, Pace NL, et al. Transient neurologic symptoms after spinal anesthesia with lidocaine versus other local anesthetics: A systematic review of randomized, controlled trials. Anesth Analg. 2005;100:1811–1816. See Also (Topic, Algorithm, Electronic Media Element)

• Epidural abscess • Epidural hematoma

CODES ICD9 • 724.2 Lumbago • 781.99 Other symptoms involving nervous and musculoskeletal systems • 782.0 Disturbance of skin sensation ICD10 • M54.5 Low back pain • R20.9 Unspecified disturbances of skin sensation • R29.818 Other symptoms and signs involving the nervous system

CLINICAL PEARLS

• Transient neurologic symptoms are characterized by transient low back pain with radiation to the buttocks and thighs. The pathophysiology remains unknown. • Diagnosis of exclusion with normal neurologic exam, radiologic imaging, and EMG testing. However, other potentially catastrophic entities such as epidural hematoma and epidural abscess should be ruled out. • Risk reduction includes avoiding of lidocaine, high doses of spinal anesthetic medications,

and vasoconstrictor additives.

TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT (TIPS) Selma Ishag, MB, BS, MD

BASICS DESCRIPTION General

• Transjugular intrahepatic portosystemic shunt (TIPS) is a percutaneous procedure that involves the creation of a tract between the portal vein and hepatic vein, under fluoroscopic guidance. It is performed to treat portal hypertension. • Portal hypertension. Esophageal varices develop at a hepatic venous pressure gradient (HVPG) of at least 10 mm Hg. Blood is diverted from the high pressure of the cirrhotic and fibrotic liver to the spleen, intestines, and stomach (creates abnormal varices). The development of ascites or variceal bleeding usually begins at 12 mm Hg. • Prior to the procedure, the patency of the portal vein is verified by ultrasound or angiography. The right internal jugular vein is accessed via needle aspiration and ultrasound guidance. The percutaneous tract is dilated and a large bore sheath is inserted into the right atrium. The right atrial pressure is measured. • A smaller catheter is then passed through the sheath (superior vena cavaright atriuminferior vena cava) and into the hepatic vein. A wedged hepatic venograph is performed, and retrograde flow of the contrast agent through the liver into the portal system provides an image of the portal vein and its branches. Iodinated contrast agents provide excellent image resolution but carry a risk of liver parenchymal injury (high viscosity) as well as anaphylaxis or renal toxicity. Carbon dioxide is often preferred as a contrast agent for its low viscosity and ease of diffusion through the sinusoids into the portal venous system. • Under guidance from the venogram images, a needle is passed within the liver parenchyma into the portal vein and direct portal vein pressures are measured. The pressure gradient between the portal vein and the right atrium is calculated (portosystemic pressure gradient). • Specialized balloon dilators are passed over the portal vein needle to create a tract through the liver parenchyma; a large bore sheath and stent are then advanced into the portal vein. The sheath is retracted and the stent is deployed. • Postdeployment, the stent is balloon angioplastied to an 8 mm diameter, initially, because too much portal vein flow bypassing the liver increases the risk of encephalopathy and can worsen liver function. The portosystemic pressure gradient is measured; if the reduction is <12 mm Hg in patients with variceal bleeding or <8 mm Hg in patients with ascites, then a 10 mm balloon is used to dilate the shunt further. • A post-insertion venography is performed to confirm adequate stent positioning and good flow through the newly created shunt. • Preexisting varices may also be embolized at this time. • Indications. Primary indications include secondary prevention of variceal bleeding and

refractory cirrhotic ascites. TIPS may be potentially beneficial in refractory, acutely bleeding varices, refractory hepatic hydrothorax, hepatorenal syndrome (HRS), failed anticoagulation in moderate Budd–Chiari syndrome, prevention of rebleeding from gastric and ectopic varices, and rebleeding after medical management in portal hypertensive gastropathy. • Absolute contraindications include primary prevention of variceal bleeding, congestive heart failure (CHF), severe pulmonary hypertension, multiple hepatic cysts, uncontrolled systemic infection, and unrelieved biliary obstruction.

Position

Supine, arms tucked Incision

• Right internal jugular access • Ultrasound guidance

Approximate Time 1–4 hours

EBL Expected

Minimal, but can potentially be massive from vessel injury combined with coagulopathy Hospital Stay 1–2 days

Special Equipment for Surgery

• Fluoroscopy, Doppler ultrasonography • Special needle sets, angioplasty balloons, endovascular stent grafts, CO2 injection apparatus. • Embolic agents may be required

EPIDEMIOLOGY Prevalence

Not available Prevalence

15,000 TIPS were performed from its first report in the 1980s till the year 2000. Morbidity

<3% major procedural complications Mortality

Immediate mortality from intraabdominal hemorrhage or right heart failure is 1.7%. ANESTHETIC GOALS/GUIDING PRINCIPLES

• A full assessment of the patient’s liver disease and concomitant organ dysfunction should be performed.

• Maintain a balance between hepatic oxygen supply and demand. – The hepatic artery supplies 30% of the liver’s blood flow and 50% of its oxygen requirement. The portal vein supplies the balance. – Autoregulation maintains hepatic blood flow by increasing hepatic arterial flow if there is a decrease in the portal vein flow. • Decreased albumin levels, impaired metabolism, and increased volume of distribution affect drug pharmacokinetics. • Consider transfusion of fresh frozen plasma and blood products prior to and during the procedure, as needed.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Variceal bleeding • Intractable ascites

History

• Advanced liver disease. • Model for end-stage liver disease (MELD) formula for risk stratification utilizes INR, bilirubin, and creatinine levels. – Best outcome with MELD score <14. – TIPS may be performed as a salvage treatment for active bleeding with a MELD score >24. – Carefully weigh risk of hepatic decompensation with the benefit of TIPS for a MELD score between 15 and 25.

Signs/Physical Exam

Hypoxemia, clubbing, cyanosis, encephalopathy, ascites, bruises, jaundice MEDICATIONS

• Nonselective beta-blockers allow unopposed alpha-mediated splanchnic vasoconstriction and should be titrated to a heart rate as low as 55 bpm or intolerance. • Diuretics. Spironolactone 400 mg and furosemide 160 mg maximum daily dose. • Lactulose

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CBC • Coagulation studies • Liver function tests • Kidney function and electrolytes • Type and Crossmatch blood • Cardiac echocardiogram to rule out CHF, portopulmonary hypertension, right-to-left shunt • Liver imaging for portal vein thrombosis, hepatic mass.

CONCOMITANT ORGAN DYSFUNCTION

• Hepatic encephalopathy • Cirrhotic cardiomyopathy: high cardiac output, impaired systolic response to stress, diastolic dysfunction as well as electrophysiologic abnormalities, mainly prolonged QTc interval putting the patient at risk of lethal arrhythmias. • Portopulmonary hypertension: Mean PAP >15 mm Hg due to an imbalance of vascular mediators, favoring vasoconstriction. • Hepatopulmonary syndrome: Increased A-a gradient due to intrapulmonary vasodilation. • Hepatorenal syndrome. Portal hypertension and splanchnic blood pooling result in relative hypovolemia and activation of the renin–angiotensin–aldosterone system. Renal vasoconstriction and hypoperfusion lead to HRS type 1 or 2 depending on the rate of progression. Carries a poor prognosis. • Coagulation disorders secondary to decreased levels of liver-dependent coagulation factors, thrombocytopenia, and fibrinolysis. • Anemia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Cautious use of benzodiazepines • Correct coagulopathies • Correct electrolytes, can cause arrhythmias

Special Concerns for Informed Consent • Blood transfusion • Possible invasive monitoring lines • Postoperative ventilator support

Antibiotics/Common Organisms

First-generation cephalosporins against skin flora INTRAOPERATIVE CARE Choice of Anesthesia

• Deep sedation may be utilized • General anesthesia should be considered in patients with a difficult airway, high risk of bleeding, aspiration, encephalopathy, anxiety, or inability to stay still. Also preferred if compromised pulmonary status from hepatopulmonary syndrome or ascites. Monitors

• Standard ASA monitors • Invasive lines are determined by the patient’s comorbidities. • Adequate IV access should be attained in the event that large volume resuscitation is

required.

Induction/Airway Management

If general anesthesia, intubation is preferred due to the limited access to the head (and increased risk for aspiration if active gastrointestinal bleeding or ascites). Maintenance

• Volatile agents: Isoflurane, sevoflurane and desflurane have the least effect on hepatic blood flow. • Neuromuscular blockade. Organ independent elimination of atracurium and cisatracurium • Opioids. The half-life is prolonged in liver disease. • Volume. Patients are intravascularly volume depleted (functionally hypovolemic) while being total body water overloaded. Judicious volume replacement with colloids, blood products, or crystalloids should be administered as appropriate. • If performed under monitored anesthesia care, judicious use of sedatives is recommended. Either propofol or dexmedetomidine may be used for maintenance of sedation. Dexmedetomidine has some analgesic effect and causes minimal respiratory depression. It may cause significant hypotension in intravascularly depleted patients, but this side effect is probably negated after diversion of portal blood into the systemic circulation.

Extubation/Emergence

Standard extubation criteria. Patients should be fully awake.

FOLLOW-UP BED ACUITY

Close monitoring for 24–48 hours ANALGESIA

Minimal requirement COMPLICATIONS

• Intraprocedural: – Carotid artery or tracheal puncture – Arrhythmias – Traversing the liver capsule is common but intraperitoneal bleeding is rare (1–2%). – Creation of an arterioportal, arteriobiliary or biliarystent fistula requires occlusion of the fistula and creation of a new shunt. – Extrahepatic puncture of the portal vein; potentially fatal – Stent displacement into the IVC, right atrium, or even the pulmonary artery. • Postprocedural: – Stent thrombosis occurs in 10–15% of patients possibly from leakage of bile into the stent (early occurrence). Less common now with PTFE covered stent grafts. – Stent occlusion from pseudointimal hyperplasia (restenosis) is common. May present with recurrence of symptoms. Surveillance is performed with Doppler ultrasound on

postprocedure day 1 and every 3 months. TIPS angiography and dilation are performed if there is evidence of occlusion clinically or on ultrasound. – Hemolysis from trauma to RBCs; resolves in 3–4 weeks. – Infection. “Endotipsitis” is rare, but requires long-term antibiotic therapy.

PROGNOSIS

• 30-day survival reaches 90% • 1-year mortality after TIPS for bleeding varices 10–52% and for ascites 24–54%. • New or worsening encephalopathy is seen in 20–30% of patients and responds to medical management but may rarely necessitate occlusion of the TIPS.

REFERENCES

1. Boyer TD. Transjugular intrahepatic portosystemic shunt: Current status. Gastroenterology. 2003;124:1700–1710. 2. Boyer TD, Haskal ZJ. The role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension: Update 2009. Hepatology. 2010;51(6):2236–2237. 3. Gaba RC, Khiatani VL, Knuttinen MG, et al. Comprehensive review of TIPS technical complications and how to avoid them. AJR. 2011;196:675–685. 4. Heidelbaugh JJ, Bruderly M. Cirrhosis and chronic liver failure: Part i. Diagnosis and evaluation. Am Fam Physician. 2006;74(5):756–762. 5. Heidelbaugh JJ, Bruderly M. Cirrhosis and chronic liver failure: Part ii. Complications and treatment. Am Fam Physician. 2006;74(5):767–776. 6. Scher C. Anesthesia for transjugular intrahepatic portosystemic shunt. Int Anesth Clin. 2009;47(2):21–28. 7. Senousy BE, Draganov PV. Evaluation and management of patients with refractory ascites. World J Gastroenterol. 2009;15(1):67–80. 8. Toubia N, Sanyal AJ. Portal hypertension and variceal hemorrhage. Med Clin N Am. 2008;92:551–574. See Also (Topic, Algorithm, Electronic Media Element) • End-stage liver disease • Hepatic encephalopathy • Radiation safety

CODES ICD9 572.3 Portal hypertension ICD10 K76.6 Portal hypertension

CLINICAL PEARLS

• Precautions of anesthesia in a remote location: Follow ASA guidelines for nonoperating room locations, maintain radiation safety, and confirm available assistance and resources (medications, transfusion requirements, etc.).

TRANSSPHENOIDAL PITUITARY RESECTION Victor Duval, MD

BASICS DESCRIPTION General

• Harvey Cushing pioneered transsphenoidal pituitary surgery in the early 1900’s. • Today, the endoscopic endonasal approach with stereotactic guidance is often a joint effort between an ENT surgeon and neurosurgeon (minimally invasive). Stereotactic imaging produces a three-dimensional map by placing an image-guidance system on the head and utilizing available CT and MRI scans in order to aid with navigating through the nose, locating the lesion, and identifying the position of surgical instruments. • The ENT surgeon performs the creation of bony openings by inserting an endoscope into a nostril and advancing it to the back of the nasal cavity. Instruments are then passed through the endoscope to remove a small portion of the nasal septum, sphenoid sinus, and sella. The neurosurgeon performs the pituitary resection with curettes. A fat graft may be needed to fill the empty space previously occupied by tumor (often attained from the abdomen). The ENT surgeon then proceeds to close the bony openings. The sella is sealed with a bone graft from the septum (or synthetic graft) and sealed with fibrin glue to prevent CSF leaks. Position

• Supine • Head on horseshoe or in Mayfield pin-head holder

Incision

No actual incision; a passage to the sphenoid sinus is established, followed by resection of the anterior and posterior walls of the sphenoid sinus Approximate Time

2–4 hours. Pathologic examination may increase anesthetic time. EBL Expected

• Usually minimal. Rapid, massive blood loss is always a possibility (rare) due to the proximity of the carotid arteries and cavernous sinus. • All patients should have a type and screen and adequate vascular access.

Hospital Stay 2–3 days

Special Equipment for Surgery • Microscope

• Stereotactic guidance • Endoscope

EPIDEMIOLOGY Prevalence

• Varies from 1 to 7 cases per 100,000 per year. • Between the years of 1996–2000, it is estimated that 5,410 cases were performed annually in US nonfederal hospitals.

Prevalence

• Autopsy studies demonstrate pituitary tumors in 14.4% of the deceased population; whereas radiologic studies suggest that it is 22.5%. • Accounts for ∼9% of all brain and CNS tumors.

Morbidity

• Tumor recurrence, CNS metastases, and, rarely, distant metastases can occur. • Surgical repair – Serious complications such as CSF leak, meningitis, stroke, intracranial hemorrhage, and visual loss occur at a rate of 1–2%. – Less severe complications such as sinus disease, nasal septal perforations, and wound problems occur at a rate of 6–7%.

Mortality

Surgical mortality is estimated at 0.4–0.9%

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The mass typically presents with one or more of the following effects: Mass effect (headaches, visual defects), or pituitary hormone hypersecretion or hyposecretion. • Patients with signs of acromegaly may be difficult to ventilate. An awake fiberoptic technique may be needed. • Blood should be readily available and IV access should be adequate to accommodate the possibility of potentially sudden and massive blood loss. • Electrolytes and volume status should be monitored frequently if signs of central diabetes insipidus (CDI) develop. • Emergence and extubation should be timed in such a way as to avoid vigorous coughing without compromising airway patency post extubation.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Patients with macroadenomas or other large suprasellar masses often present with headaches, visual field defects, and hypopituitarism. • Large masses can also cause syndrome of inappropriate antidiuretic hormone (SIADH) and hydrocephalus.

• Prolactin secreting microadenomas often present with secondary amenorrhea. • Growth hormone secreting tumors lead to acromegaly. • Adrenocorticotropic hormone secreting tumors usually cause Cushing’s disease. • Thyroid secreting tumors often result in hyperthyroidism.

History

Patients with suprasellar pathology tend to be younger and relatively free of comorbid medical conditions unrelated to their primary lesion. Signs/Physical Exam

• Particular attention should be paid to the airway exam in patients with suspected acromegaly. • Patients with Cushing’s disease often show characteristics of excess endogenous corticosteroid secretion such as hypertension, truncal obesity, moon facies, thin skin, and fragile cutaneous veins. MEDICATIONS

• Patients with hyperthyroidism may be on beta-blockers and/or antithyroid drugs, such as methimazole and propylthiouracil. • Patients with growth hormone secreting tumors may be on antihypertensive medications.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Type and screen all patients. • Baseline hemoglobin concentration may be useful. • A basic metabolic panel should be reviewed in patients with suspected systemic involvement. CONCOMITANT ORGAN DYSFUNCTION

Excess growth hormone secretion can lead to hypertensive cardiovascular disease, diabetes mellitus, and impaired renal function.

TREATMENT PREOPERATIVE PREPARATION Premedications

Anticholinergics, anxiolytics, and airway topicalization may be necessary for patients with acromegaly requiring an awake fiberoptic intubation (AFOI) Special Concerns for Informed Consent

• Airway management if AFOI is planned. • Possibility of blood transfusion for all patients.

Antibiotics/Common Organisms

Third-generation cephalosporin, such as cefazolin for prophylaxis against nasopharyngeal flora INTRAOPERATIVE CARE Choice of Anesthesia

General endotracheal anesthesia for airway protection Monitors

• ASA standard monitors • Two large bore IVs • Consider arterial line for monitoring BP, hemoglobin concentration, and sodium levels.

Induction/Airway Management

• Routine induction and laryngoscopy; consider an oral RAE. • Consider AFOI in patients with acromegaly due to large tongue, decreased hyomental distance, and long epiglottis.

Maintenance

• Balanced anesthetic technique based on physician preference • No contraindication to nitrous oxide. Although some choose to avoid it, it may help attain goals for emergence. • Hypotension can develop secondary to blood loss, diabetes insipidus (DI), or hypopituitarism.

Extubation/Emergence

• Closure can be rapid if no fat graft is placed. The surgeon may request a Valsalva maneuver to check for a CSF leak. If a leak persists, a lumbar drain will be placed. • The surgeon will pack the nose at the end of the case. • Vigorous coughing should be avoided; however, deep extubation is discouraged due to the increased risk of aspiration. • Pneumocephalus can also result if positive pressure ventilation is required to treat post extubation airway compromise. • PONV prophylaxis should be given to avoid increased intracranial pressure, which can lead to CSF leak, and exposure of the surgical site to gastric contents. • Intraoperative neurologic injury secondary to hypoperfusion or pneumocephalus may lead to delayed emergence. A head CT should be obtained if the patient does not regain consciousness.

FOLLOW-UP BED ACUITY

• Intensive care unit or neuroobservation unit • Strict ins & outs

ANALGESIA

Pain is usually mild to moderate and responds well to IV narcotics. COMPLICATIONS

• Large, invasive tumors are associated with a higher rate of complications. • Hemorrhage is the most significant intraoperative complication to prepare for since it can be sudden, massive, and difficult to control. • CDI; more common with larger masses and those located posteriorly. It can present anytime from the intraoperative period to 48 hours postoperatively. Urine output and electrolytes should be monitored frequently if it is suspected. The treatment includes volume replacement and administration of DDAVP (desmopressin) • CSF leak • Air embolus can also occur in the setting of cavernous sinus injury.

PROGNOSIS

• The post surgical prognosis is very good. • Endocrine dysfunction can be corrected. On the other hand, end-organ damage from uncorrected deficiencies may be irreversible.

REFERENCES

1. Barker FG, Klibanski A, Swearingen B. Transsphenoidal surgery for pituitary tumors in the United States, 1996–2000: Mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab. 2003;88(10):4709–4719. 2. Ciric I, Ragin A, Baumgartner C, et al. Complications of transsphenoidal surgery: Results of a national survey, review of the literature, and personal experience. Neurosurgery. 1997;40(2):225–236. 3. Ezzat S, Asa SL, Couldwell WT, et al. The prevalence of pituitary adenomas: A systematic review. Cancer. 2004;101(3):613–619. 4. Jaffe RA. Intracranial Neurosurgery. Section 1.1. Anesthesiologist’s Manual of Surgical Procedures, 4th edn. Philadelphia, PA: Lippincott Williams & Wilkins, 2009. 5. Nemergut EC, Dumont AS, Barry UT, et al. Perioperative management of patients undergoing transsphenoidal pituitary surgery. Anesth Analg. 2005;101:1170–1181. See Also (Topic, Algorithm, Electronic Media Element)

• Acromegaly • Hyperthyroidism • Cushing’s disease • Syndrome of inappropriate antidiuretic hormone (SIADH) • Venous air embolism • Diabetes insipidus

CLINICAL PEARLS

• Patient characteristics and surgical factors can present a challenge to airway management. A thorough assessment of the airway is critical to key decisions that must be made at the

beginning and end of the anesthetic management for these cases. • Preparations must be made for the potential for large, rapid blood loss. • Intraoperative and postoperative hypotension can be common and multifactorial. Close monitoring of fluid status and urine output is important in diagnosis and treatment.

TRAUMA

Shreyas Bhavsar, DO

BASICS DESCRIPTION

• Trauma is the leading cause of death in the first four decades of life. • Of traumatic deaths, 50% occur immediately while 30% occur within one to a few hours after injury; this is known as the “golden hour” rule. Hemorrhagic shock is the leading cause of early death. PHYSIOLOGY PRINCIPLES

Initial assessment consists of a primary and secondary survey. • Primary survey: Addresses the “ABCDE” – airway, breathing, circulation, disability, and exposure. Goal: Start resuscitation and control hemorrhage – Airway: Secure airway in an obtunded/comatose patient, GCS <8, or potential airway obstruction due to blood, facial fractures, etc. – Breathing: Determine adequacy of ventilation and respiratory quality. Look for cyanosis, retractions, stridor, flail chest, tracheal shift, breath sounds, subcutaneous emphysema – Circulation: Assess pulse rate, pulse pressure, BP, and peripheral circulation (capillary refill, temperature of extremity, color). Control hemorrhage and replace intravascular volume. Physiologic changes seen with degree of hemorrhage: Stage 1 (<15% blood loss): Mild tachycardia (100–120 bpm); compensation with vascular constriction allows maintenance of BP, urine output, pulse pressure, respiratory rate, and mental status. Pallor may be noted, but capillary refill is generally normal. Stage 2 (15–30%): Tachycardia, hypotension, decreased urine output, pulse pressure narrowing from rise in diastolic pressure, mild tachypnea, anxiety, sweating from sympathetic response, delayed capillary refill. Stage 3 (30–40%): Classic signs of hypovolemic shock begin, including marked tachycardia (>120 bpm), hypotension, marked tachypnea (>30 bpm), altered mental status, sweating with cool, pale skin, worsening oliguria, delayed capillary refill. Stage 4 (>40% blood loss): Weak pulse with severe tachycardia, severe tachypnea, dropping systolic BP (often <70 mm Hg), decreased level of consciousness, skin is sweaty, cool, and extremely pale, anuria. • Secondary survey – Continue resuscitation – Continue search for, and repair of, potential injuries. – Perform lab tests and diagnostic studies. The serum hemoglobin and hematocrit are often not reliable indicators of acute blood loss (patients bleed whole blood). PHYSIOLOGY/PATHOPHYSIOLOGY • Neurological

– Subdural/epidural hematoma – Cerebral contusion/concussion – Increased intracranial pressure (ICP) and imminent brain herniation • Airway – Mandible, maxilla, larynx, trachea, dental trauma • Respiratory – Pneumothorax (tension, hemothorax) – Pulmonary contusion – Acute respiratory distress syndrome (ARDS): Characterized by a PaO2/FiO2 ratio of <200

and patchy bilateral infiltrates on chest radiograph without evidence of cardiogenic etiology. – Diaphragmatic injury – Broken ribs: Ranges from a single rib to flail chest (several ribs broken in multiple places that results in paradoxical chest wall movements). Can result in pneumothorax or pulmonary contusion. Suspect severe mechanism of injury and other injuries whenever 1st rib fracture is seen. – Fat emboli from long bone fractures • Cardiac – Shock is the clinical manifestation of decreased perfusion to end organs. It is characterized by hypotension, tachycardia, acidosis, large base-deficit, and increased serum lactate levels. Treatment includes fluids (crystalloids, colloids), blood products (packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate), vasopressors, and treatment of underlying cause (antibiotics for septic shock, blood for hemorrhagic shock). The endpoint of shock resuscitation is normalization of hemodynamic parameters, acidosis, lactate levels, and base-deficit. – Contusion: Can be associated with hypotension, leak of cardiac enzymes into serum, and dysrhythmias – Tamponade: If severe, can lead to Beck’s triad (hypotension, distended jugular veins, and muffled heart sounds). Can see pulsus alternans on EKG and systolic BP drop by 10 mm Hg with deep inspiration (pulsus paradoxus) • Vascular – Traumatic aortic dissection: Should be suspected whenever a widened mediastinum is seen on chest x-ray. Usually associated with severe deceleration injury pattern. • GI – Aspiration of blood or gastric contents – Blunt/penetrating abdominal trauma – Abdominal compartment syndrome – Increased intestinal permeability • Renal – Hematuria, urethral tract injury, bladder rupture • Musculoskeletal – Fractures (open, closed) – Crush injuries – Compartment syndrome

– Burns • Inflammatory consequences. Major trauma has several inflammatory manifestations including severe tissue injuries, hemorrhagic shock, and ischemia-reperfusion consequences. – An uncontrolled inflammatory process may play a key role in the development of multiple organ dysfunction, resulting in an increase in post-traumatic delayed morbidity and mortality (1). – IL-6 levels increase and are sustained, representing a major determinant of the magnitude of the hypothalamic–pituitary–adrenal (HPA) axis responses, especially cortisol secretion to stressors (4). – Adrenocortical dysfunction and vasopressor dependency have been reported (2). Cardiovascular collapse can mimic septic shock. Cosyntropin stimulation testing can confirm the diagnosis and prevent unnecessary steroid administration (3). The cosyntropin stimulation test takes over an hour for results to be interpreted (baseline cortisol levels must be drawn and then compared to levels taken after 1 hour of injection of cosyntropin). In the OR, its applicability is limited; thus in extremis, where the BP is not responsive to vasopressors, adrenal insufficiency should be considered and treated with dexamethasone 10 mg IV (will not interfere with cosyntropin test) or preferably with hydrocortisone 100 mg.

PERIOPERATIVE RELEVANCE

• Depressed consciousness: Leads to hypoventilation, inability to protect airway, gastric aspiration, and limited history and physical exam that can lead to missed injuries. • Premedication. Time permitting, nonparticulate antacid, H2 blocker, and/or metoclopramide should be considered. • Monitors – Standard ASA monitors – Foley catheter – Peripheral nerve monitor – BIS monitor. Intraoperative awareness and recall can reach 43% in serious trauma compared with 11% is less serious cases (6). – ICP monitoring Consider when mechanism of injury involves head trauma where cerebral edema and mass effect can lead to cerebral ischemia Monitoring is important to establish hemodynamic parameters and institute medical/surgical treatments of elevated ICP to help prevent brain herniation – Initially, peripheral large bore IVs. Consider central access to aid with volume resuscitation or for additional IV access. • Induction. – Preoxygenate with 3–5 large vital capacity breaths at an FIO2 of 1.0 (or 5 minutes with

tidal volume breathing). – IV induction is faster in patients with intravascular volume depletion and increased free concentration of drug (loss of plasma binding proteins). The induction agent needs to be chosen while considering the patient’s overall volume status. Ketamine (sympathomimetic properties) and etomidate (stable hemodynamic parameters) are commonly chosen. Both,

however, can cause hypotension in some situations; etomidate can impair adrenocortical function with a single induction dose. – Volatile anesthetics: Alveolar and brain concentrations increase quickly due to low cardiac output states. – Regional anesthesia: May be considered as a sole anesthetic in patients who have isolated orthopedic injuries or for postoperative analgesia. Prior to a neuraxial block placement, coagulation status should be assessed. Additionally, local anesthetics can block sympathetics and compound hypotension in already hypovolemic patients (5). • Airway – No C-spine issues (gun shot or stabbing): Rapid sequence intubation with cricoid pressure and induction agent like succinylcholine or high-dose rocuronium. – C-spine injury should be suspected until proven otherwise in patients with altered levels of consciousness, tenderness to palpation or neck pain, distracting injury, neurological deficit, and intoxication. Avoid neck hyperextension Use jaw thrust maneuver for airway manipulation Manual in-line stabilization to secure airway Direct laryngoscopy may be difficult (prepare for Bullard scope, Airtraq, GlideScope, lightwand, intubating LMA, or fiberoptic bronchoscope) Consider prepping and draping the neck for an emergent surgical airway prior to induction, if difficulty suspected • Maintenance – Minimum alveolar concentration (MAC) in hypovolemic patients may be reduced by 25%. – IV scopolamine may be utilized for patients in extremis who cannot tolerate the hypotensive or sympatholytic effects of anesthetics. It is a good amnestic and has sedative properties. • Hypothermia can result in coagulopathy and dysrhythmias as well as delayed emergence, decreased cardiac contractility, cold diuresis, impaired wound healing, and decreased metabolism of drugs • Blood products – pRBC transfusion: Ideally transfuse type and crossed blood. If time does not permit, uncrossmatched O negative blood may be utilized – Complications of pRBC infusion: Hypothermia, hyperkalemia, allergic reaction, incompatibility, infection. Early transfusion (<24 hours from hospital admission) is also an independent risk factor for the development of ARDS (7). – Coagulopathy. Dilutional thrombocytopenia is the most common and should be considered whenever the blood volume that is transfused is equivalent to the patient’s total blood volume. Coagulation factors also decrease during massive transfusion and contribute to coagulopathy. Transfusion should be guided by laboratory confirmed abnormalities. – Damage control resuscitation (DCR). A growing body of evidence shows that increased ratios of FFP:RBC and PLT:RBC transfusion improves survival in patients with severe hemorrhage. The optimal ratio remains unknown but “early and often” seems to be getting more attention to avoid coagulopathy, acidosis, and hypothermia (8). • Always consider other undiagnosed injuries when hemodynamic parameters change for the

worse or do not improve with resuscitation/surgery • Intoxication – Acute alcohol ingestion can depress MAC, chronic alcohol abuse increases MAC, and risk of delirium tremens – Acute cocaine intoxication can cause hypertension and dysrhythmias.

Pregnancy Considerations

• Airway can be difficult due to pregnancy-related airway changes and also from potential Cspine injury and immobilization. • Left uterine displacement can avoid aorto-caval syndrome. • Consult OB early if the fetus is viable (generally after 24 weeks gestation) • Emergency C-section may be required for fetal distress • Trauma can induce preterm labor (<37 weeks gestation) • Physiologic anemia of pregnancy and/or ongoing blood loss can complicate management.

REFERENCES

1. Moore FA, Moore EE. Evolving concepts in the pathogenesis of postinjury multiple organ failure. Surg Clin North Am. 1995;75:257–277. 2. Hoch RC, Rodriguez R, Manning T, et al. Effects of accidental trauma on cytokine and endotoxin production. Crit Care Med. 1993;21:839–845. 3. Claussen MS. Acute adrenal insufficiency presenting as shock after trauma and surgery: Three cases and review of the literature. J Trauma. 1992;32(1):94–100. 4. Mastorakos G, Chrousos GP, Weber JS. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab. 1993;77:1690– 1694. 5. Gregoretti C, Decaroli D, Miletto A, et al. Regional anesthesia in trauma patients. Anesthesiol Clin. 2007;25(1):99–116, ix–x. 6. Lubke GH, Kerssens C, Phaf H, et al. Dependence of explicit and implicit memory on hypnotic state in trauma patients. Anesthesiology. 1999;90(3): 670–680. 7. Benson AB, Moss M. Trauma and acute respiratory distress syndrome: Weighing the risk and benefits of blood transfusions. Anesthesiology. 2009;110(2):216–217. 8. Johansson PI, Stensballe J. Hemostatic resuscitation for massive bleeding: The paradigm of plasma and platelets- a review of the current literature. Transfusion. 2010;50:701–710. See Also (Topic, Algorithm, Electronic Media Element) • Spinal cord injury • Hypothermia • Cocaine • Blood transfusion

CODES

ICD9

• 958.4 Traumatic shock • 959.9 Unspecified site injury ICD10

• T14.90 Injury, unspecified • T79.4XXA Traumatic shock, initial encounter

CLINICAL PEARLS

• In trauma patients, always suspect that patients have – A “full stomach” – A cervical spine injury – Other injuries or worsening of current injuries when hemodynamic parameters change • Agitation/combative behavior is not always intoxication from substance abuse. Consider pain, hypoxia, intracranial injury, full bladder, electrolyte imbalance.

TREADMILL STRESS TEST (TMST) Kenneth F. Kuchta, MD

BASICS DESCRIPTION

• A treadmill stress test (TMST) is a traditional screening test for coronary artery disease that is perhaps the least invasive and most cost effective, while retaining a reasonable sensitivity and specificity. • Patients with coronary and cardiac disease may have normal resting EKGs; however, by increasing the oxygen demand, signs of heart disease may be unmasked. • A TMST is thus used to diagnose coronary artery disease, determine functional capacity, and estimate prognosis in a variety of settings – Evaluation of chest pain – Known or suspected coronary artery disease – Follow-up after myocardial infarction – Valvular heart disease – Follow-up after revascularization – Preoperatively to provide a measure of functional cardiovascular status and, perhaps even more important, may identify patients at risk for intraoperative ischemic events. • Semantically a “treadmill stress test” only describes the mechanism used to stress the heart, not the means of detecting ischemia. Traditionally continuous EKG monitoring was used, but more recently thallium or other nuclear medicines or echocardiography is being used to detect ischemia even when the stressor is exercise via a treadmill. As these versions of stress tests are covered elsewhere in this book, this chapter will be limited to a stress test with treadmill exercise as the stressor, while EKG monitoring is used to detect ischemia (what could be more accurately called a treadmill EKG). PHYSIOLOGY PRINCIPLES

• The heart is essentially an aerobic organ with a limited ability to obtain energy from aerobic metabolism. Furthermore, at rest, oxygen extraction from the coronary circulation is near maximal. • With increased oxygen demand from exercise (in a TMST) or from stress during surgery, the myocardium attempts to increase oxygen delivery by increasing coronary blood flow (via decreasing vessel resistance with vasodilation; in patients with coronary artery disease, this ability is often limited). • The TMST, thus, attempts to mimic the stress of the surgical procedure in an attempt to estimate the propensity for ischemia. • Procedure – Preparation: Appropriate cardiac evaluation, including a history and physical – Monitors: Placement of EKG electrodes (12-lead) for continuous monitoring and a noninvasive BP cuff. Baseline measurements are taken.

– Exercise protocol: The Bruce protocol is most commonly utilized (others can be used). It starts off with a slow speed; the workload is raised in stages, comprised of 3-minute intervals with the protocol dictating the speed and slope. The EKG is continuously monitored, and the BP is typically recorded during the second minute of each stage (may be done more frequently, as needed). – Exercise end point: Achieving a target heart rate that is 85% of the maximal predicted for the patient’s age is a commonly used endpoint to assure an adequate level of stress is attained. For example, a 50-year old has a maximal predicted heart rate of 170; thus a target heart rate is 144. Workload or time limit is also occasionally used. – Elements involved in the interpretation Baseline EKG Duration of the exercise period Maximal heart rate Workload in METS EKG findings: ST segment changes, arrhythmias BP changes Symptoms during exercise Other subjective comments may also be included

ANATOMY

• The EKG leads represent the electrical function of the heart in different trajectories; it is a 2dimensional assessment. Because the heart is a 3-dimensional organ, several leads are utilized. Normal function or abnormalities may be extrapolated to the likely arterial supply; however, anatomical variations require that invasive testing be performed to accurately identify diseased vessels. • Inferior leads (II, III, and aVF): Inferior heart muscle; usually supplied by the right coronary artery. • Lateral leads (aVL, I, V5, and V6): Lateral wall of the left ventricle; usually supplied by branches of the left circumflex and left anterior descending artery. • Anterior leads (V3 and V4): Anterior wall of the heart; usually supplied by the left anterior descending artery. • Septal leads (V1 and V2): Intraventricular septum; branches of the left anterior descending artery usually supply the anterior two-thirds of the septum.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The specific criteria for interpretation may vary. – The most important finding is ST segment elevation or depression (greater than or equal to 1 mm horizontal or downsloping for at least 60–80 millisec) – Other findings may also suggest (or support) the presence of ischemia: Chest pain consistent with angina A drop in systolic pressure of more than 10 mm Hg Development of a S3 or S4 murmur may indicate myocardial dysfunction and ischemia Development of significant arrhythmias (VT, premature ventricular contractions [PVCs], tachyarrhythmias) or EKG changes (type I atrioventricular block [AVB], bundle branch block [BBB], hemiblocks, AV conduction abnormalities, T-wave flattening, P-wave

changes) • Results are usually reported as – Positive: High probability of ischemia – Negative: Low probability of ischemia (hopefully with an adequate level of stress) – Inconclusive (e.g., the development of arrhythmias without ST segment changes) – Uninterpretable tests can also be reported due to Equipment failure Inability to complete the exam (which may be due to deconditioning, fatigue, claudication, or lack of cooperation) Beta-blockade or intrinsic slow heart rate (as in a pacer dependent patient) can also prevent achieving maximal predicted heart rate. • The results are often further qualified by whether the patient achieved the exercise goal (supramaximal) or failed (submaximal). • A positive test in the preoperative period will usually lead to a cardiac catheterization to verify the diagnosis and help plan for possible intervention (e.g., angioplasty or cardiac surgery). Inconclusive results and uninterruptible tests may lead to an alternate stress test or cardiac catheterization.

PERIOPERATIVE RELEVANCE

• Coronary artery disease. Patients presenting for surgery may have known disease or occult disease that could otherwise manifest in the perioperative period. – Advanced age, hypertension, hypercholesterolemia, and tobacco use are risk factors for coronary artery disease that are often seen in patients presenting for surgery. – Diabetes is not only a risk factor but can also increase the chance for silent ischemia. – Peripheral vascular disease is strongly associated with coronary artery disease (∼twothird of patients have significant coronary artery disease). Claudication can frequently limit exercise tolerance and the ability to achieve exercise goals (submaximal). • Exercise tolerance. A patient’s exercise tolerance is the cornerstone of a cardiovascular evaluation, often determining when to perform a stress test preoperatively. As noted, however, diabetes and claudication can limit this evaluation.

EQUATIONS

Maximum Predicted Heart Rate = 220–age (acceptable exercise endpoint is 85% of this value)

REFERENCES

1. Gibbons RJ, Balady GJ, Bricker JT, et al. ACC/AHA 2002 guideline update for exercise testing: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). American College of Cardiology. Website. Available at www.acc.org/clinical/guidelines/exercise/dirIndex.htm. 2. Rodgers GP, Ayanian JZ, Balady G, et al. American College of Cardiology/American Heart Association Clinical Competence Statement on Stress Testing. A Report of the American College of Cardiology/American Heart Association/American College of Physicians– American Society of Internal Medicine Task Force on Clinical Competence. Circulation.

2000;102:1726–1738.

See Also (Topic, Algorithm, Electronic Media Element) • Coronary artery disease • Premature ventricular contractions • 12-lead EKG • Coronary arteries • Perioperative statins

CODES ICD9

V81.2 Screening for other and unspecified cardiovascular conditions ICD10

Z13.6 Encounter for screening for cardiovascular disorders

CLINICAL PEARLS

• Limitations to performing the procedure or interpreting the results: – Inability to walk long distance (as in claudication or in deconditioned patients) – Presence of a BBB (making ST segment interpretation difficult) – Inability to increase heart rate (due to beta-blockers or patients who are pacer dependent). • Traditionally cardiac stress tests are used to identify patients at risk for ischemia triggering coronary angiography and possible angioplasty or CABG in order to decrease the risk of the originally proposed surgery. This paradigm has several limitations: – While those returning for surgery after coronary artery bypass grafting have a lower cardiovascular risk, the morbidity and mortality of heart surgery is not insignificant. – Coronary angioplasty and stenting may not change long-term outcome and may delay needed surgery because of the need for anticoagulation. – Protective interventions such as beta-blockade and statins have been shown to decrease cardiac morbidity and mortality in high risk or cardiovascular patients.

TRICUSPID ATRESIA Nirvik Pal, MD

BASICS DESCRIPTION

• Tricuspid atresia (TA) is a congenital heart disease with maldevelopment of the tricuspid valve (TV); it leads to restriction of blood flow from the right atrium (RA) to the right ventricle (RV). • Nevertheless, it is a “univentricular heart” with a single left physiologic ventricle that supplies both the systemic and pulmonary circuits in parallel. EPIDEMIOLOGY Prevalence

• Comprises 1–3% of all congenital heart disease. • Other defects are present in close to 20% of patients with TA

Morbidity

• Failure to thrive • Congestive heart failure (CHF)

Mortality

• Without surgical correction, ∼60% will die in infancy • Operative mortality <2%.

PHYSIOLOGY/PATHOPHYSIOLOGY

• With normal cardiac physiology, blood return to the heart enters the RA and then flows to the RV via the tricuspid valve. However, TA prevents normal flow, and intra-atrial communication with the RA must exist (right-to-left shunting). • Pulmonary blood flow (PBF) is dependent on the individual anatomy. It can arise from the – Physiologic (left) single ventricle – Rudimentary RV – Patent ductus arteriosus (PDA) • Ratio of systemic vascular resistance (SVR) to pulmonary vascular resistance (PVR) determines the blood flow pattern. – High PVR results in more blood flow to the systemic circuit as well as cyanosis and hypoxemia. – High SVR results in more blood flow to the pulmonary circuit. This can result in signs and symptoms of CHF. • Mixing of oxygenated and deoxygenated blood takes place through the – PFO/ASD – VSD (if present)

• Left ventricle. Functions as the single ventricle. With time, the volume overload and chronic hypoxemia can impair its function and result in – Decreased ejection fraction – Mitral annular dilatation – Mitral insufficiency

ANESTHETIC GOALS/GUIDING PRINCIPLES

Maintain a “Cardiac Grid”: • Heart rate: Appropriate for age and sinus rhythm • Contractility: Preserve cardiac contractility (avoid cardiodepressant drugs) • Preload: Optimize preload • SVR: In patients with low PBF, maintain high SVR to promote PBF and oxygenation. In those with high PBF, maintain low SVR to promote forward systemic flow and prevent pulmonary edema. • PVR: In low PBF, reduce the PVR. In high PBF, elevate the PVR. Maintain adequate functional residual capacity (FRC) for optimal ventilation without hemodynamic compromise.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Failure to thrive • Shortness of breath

History

• May present early or late depending on the extent and severity of the lesion. • Tachycardias • “Black-outs” (stroke/dysrhythmia)

Signs/Physical Exam

• Reduced PBF: Severely reduced oxygen saturation, cyanosis • Excess PBF: Normal oxygen saturation and reduced lung compliance may lead to ventricular failure and dilatation with CHF. • Low cardiac output state: Moderately reduced oxygen saturation, low mixed venous oxygen saturation, metabolic acidemia, hepatomegaly, peripheral edema, raised jugular venous pulsation. • Single second heart sound, moderate systolic murmur • Clubbing of fingers

TREATMENT HISTORY

• Goal: Heart transplantation or prevent or delay the development of pulmonary hypertension by reconstruction of the “series” circuit between the systemic and pulmonary circulations. Essentially this would mean a “single/one ventricle repair” (Fontan circulation) that may need several staged procedures.

– Stage I: (0–6 months) goal is to balance between the pulmonary and systemic blood flow and permit growth of the PA. In patients with a low PBF, shunt operations are performed (e.g., modified Blalock–Taussig shunt) and in those with high PBF, PA banding may be performed to restrict blood flow to the lungs. – Stage II: (4–8 months) goal is to maintain the balance between pulmonary and systemic blood flow as the child soon starts outgrowing the prior shunt. A bidirectional Glenn shunt or a hemi-Fontan procedure is often performed at this time. Also known as a single cavopulmonary connection (SVC connected to PA). – Stage III: (15 months–3 years) goal is to completely redirect the systemic blood flow to the pulmonary circuit in a series fashion (Fontan physiology). Essentially, it is the total cavopulmonary connection (along with SCV, even the IVC is connected to PA). Often the completion of this procedure needs to wait so as to achieve adequate (single) ventricular compliance at the new end-diastolic volume.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Hemoglobin • Coagulation tests, liver function tests (assess synthesis of coagulation factors) • EKG: Left-sided ST and T-wave abnormalities. • CXR: Cardiomegaly (in CHF), accentuated pulmonary vasculature depending on the PBF. • Echocardiogram: TA, ASD, hypoplasia of the RV. Also may show VSD, coarctation of the aorta, subaortic stenosis, TGA. Assess for ventricular dysfunction • Catheterization: Confirm the position of the great vessels, evaluate hemodynamics (pulmonary vascular pressures).

CONCOMITANT ORGAN DYSFUNCTION • Polycythemia • Coagulopathies • Dysrhythmias • Cerebrovascular accidents

CLASSIFICATIONS

TA: • Type I: Normal relationship of great vessels (69%) – IA: No VSD with pulmonary atresia (9%) – IB: Restrictive VSD with pulmonary stenosis (51%) – IC: Nonrestrictive VSD with no pulmonary stenosis (9%) • Type II: d-transposition of great vessels (28%) – IIA: VSD with pulmonary atresia (2%) – IIB: VSD with pulmonary stenosis (8%) – IIC: VSD with no pulmonary stenosis (18%) • Type III: l-transposition of great vessels: (3%)

TREATMENT

PREOPERATIVE PREPARATION Premedications

Avoid oversedation to prevent hypoxemia or hypercapnia. If necessary, can consider midazolam intranasal. Special Concerns for Informed Consent

Consider phlebotomy for patients with very high hematocrits (>70%) and presenting with altered mental status due to sluggish circulation. INTRAOPERATIVE CARE Choice of Anesthesia General anesthesia Monitors

• Standard ASA monitors • Intra-arterial BP monitoring • Central venous catheters may predispose to thrombosis, may consider direct transthoracic left atrial line placement.

Induction/Airway Management

Balanced anesthesia technique with inhaled or IV induction. Maintenance

• Management of PVR – Depends on the size of the PAs and pulmonary arteriolar resistance that in turn depends on PaO2, pH, PaCO2, and sympathetic stimulation. Decreases in the PaO2 or pH decrease

the PBF; whereas, increases in the later two increase the PBF. Depending on the presentation (reduced PBF or increased PBF), maneuvers can be implemented to manipulate the PBF. • Post-CPB both for partial and total cavopulmonary connection – Maintenance of optimal FRC (avoid under and over distension of the lungs); normocapnia with an optimal respiratory rate (<20/minute), inspiratory time (<1 second), and peak end-expiratory pressure (PEEP) (<6 mm Hg). – Modified ultrafiltration (MUF) post-CPB has been associated with reduced postoperative blood loss and improved lung function. – Nitric oxide may be utilized for persistent elevated PA pressure. – Myocardial dysfunction may need inotropic support with dopamine. Inodilators like milrinone may decrease PA pressures while augmenting contractility/ejection fraction. – Mild hypercapnia. In cases of partial cavopulmonary connection (Glenn shunt/hemiFontan) a PaCO2 of 45–50 mm Hg may increase the cerebral blood flow and eventually PBF through SVC–PA connections; can improve systemic oxygenation. • Total pulmonary venous connections are often fenestrated at the tunnel so as to provide some ventricular preload at the expense of momentary desaturation which may happen due

to hypovolemia or a sluggish circulation. This may often be indicated by systemic saturation below 85% and a low mixed venous saturation. A gradient of 7 mm Hg between the left atrial pressure (LAP) and the right atrial pressure (RAP) is generally adequate to maintain a passive forward PBF (1,2).

Extubation/Emergence

Both in partial and total cavopulmonary connections, early extubation is most favored due to better hemodynamics and PBFs achieved with spontaneous ventilation.

FOLLOW-UP BED ACUITY

• All patients after any stage of repair require an ICU stay until stabilized hemodynamically. • Patients having a noncardiac surgery who had a repair of TA before, may need either ICU admission or HDU care postoperatively depending on the nature of surgery and the pathophysiologic and functional status of the patient preoperatively.

MEDICATIONS/LAB STUDIES/CONSULTS

• Treating cardiologist: For insight into the current status of the patient. • Hematologist: If phlebotomy is considered.

COMPLICATIONS

• Hypoxemia: More commonly seen after partial cavopulmonary connections. Normal FRC, PaCO2, respiratory rate, short inspiratory time, and minimal PEEP may help. • Low cardiac output state: More commonly seen after a total cavopulmonary connection. Correction of volume status, mechanical ventilation, and supportive inotropes should help. • Arrhythmias: Tachyarrhythmias are poorly tolerated; they limit PBF during diastole. • Sequela: Arrhythmias, thrombosis, ventricular dysfunction, and protein losing enteropathy. • Noncardiac surgery, post-Fontan: Increased blood loss due to high venous pressure and coagulopathy, optimal ventilation strategy, maintain euvolemia. It is imperative to discuss the anatomy and physiological state of the patient with the patient’s cardiologist. • AndropoulosDB, StayerSA, Rusell IA.Anesthesia for the Patient with a Single Ventricle. Anesthesia for Congenital Heart Disease,2nd edn. Hoboken, NJ: Wiley-Blackwell, 2009.

REFERENCES

1. Lake CL, Booker PD, et al. Tricuspid Atresia. Pediatric Cardiac Anesthesia, 4th edn. Philadelphia, PA: Lippincott Williams & Wilkins, 2005. 2. Donotrio MT, Jacobs ML, Spray TL, et al. Acute changes in preload, afterload and systolic function after superior cavopulmonary connections. Ann Thorac Surg. 1998;65:503–508. 3. Li J, Hoskote A, Hickey C, et al. Effect of carbon dioxide on systemic oxygenation, oxygen consumption, and blood lactate levels after bidirectional superior cavopulmonary anastomosis. Crit Care Med. 2005;33:984–989. 4. Mott AR, Alommrani A, Tortoriello TA, et al. Changes in cerebral saturation profile in

response to mechanical ventilation alterations in infants with bidirectional superior cavopulmonary connections. Pediatr Crit Care Med. 2006;7:346–350.

ADDITIONAL READING

• Rosenthal A,Dick M. Tricuspid atresia. In:Adams FH, EmmanouilidesGC, Riemenschneider TA (Eds),Moss’ `Heart Disease in Infants, Children and Adolescents,’ 4thedn. Baltimore: Lippincott, Williams &Wilkins, 1989:903. See Also (Topic, Algorithm, Electronic Media Element)

• Patent ductus arteriosus • Ventricular septal defect (VSD)

CODES ICD9 746.1 Tricuspid atresia and stenosis, congenital ICD10 Q22.4 Congenital tricuspid stenosis

CLINICAL PEARLS

• A thorough understanding of the current hemodynamic status of the patient is necessary. • In patients with low PBF: Management is directed toward increasing the PBF. • In patients with high PBF: Management is aimed at reducing the PBF and preventing or aggravating the onset of CHF.

TRISMUS

Thomas I. Epperson III, MD Joseph R. Whiteley, DO

BASICS DESCRIPTION

• Trismus is defined as the complete inability to open the mouth and can result from a number of causes ranging from preexisting pathology to acute intraoperative pathology • Perioperatively, trismus may result in difficulty with securing the airway or as a precursor of malignant hyperthermia (MH). EPIDEMIOLOGY Prevalence

Seen in 1–4% of general anesthetic cases Prevalence

More common in pediatrics; 40–50% of cases are seen in patients less than 10 years of age. Morbidity

Associated with MH. 40–50% of trismus patients have a positive halothane contracture test. Mortality

• Death in less than 1% from lost airway • One to five percent mortality from treated MH.

ETIOLOGY/RISK FACTORS

• Pediatrics <10 years of age – Patients with an increased association for MH such as Duchenne’s muscular dystrophy, central core disease, osteogenesis imperfecta, and King–Denborough syndrome. – Strabismus surgery has a slight increased risk. • Preexisting pathologic processes – Peritonsillar abscesses – Temporomandibular disorder (TMD) – Bruxism – Pericoronitis – Tetanus – Radiation or surgery to the head or neck • Medications such as amphetamines

PHYSIOLOGY/PATHOPHYSIOLOGY

• Trismus describes a common end-point of an inability to open the mouth.

• MH. Trismus is a feared predecessor of MH; it has a demonstrated association. MH is a pharmacogenetic disorder of the ryanodine receptor. It is characterized by the triggering of acute skeletal muscle hypermetabolism with increased oxygen consumption and carbon dioxide production. • Peritonsillar abscess from tonsillitis • Temporal mandibular joint disorders • Bruxism (grinding of teeth) is often seen in patients in a coma and can lead to trismus. It may be relieved by botulin toxin injection. • Pericoronitis describes inflammation around the crown of a tooth resulting from an infection. • Tetanus can result from the bacteria Clostridium tetani and describes the toxicity to nerves that leads to muscle rigidity or “lock jaw.” • Radiation or surgery to the head and neck • Medications – Injection of local anesthetics can cause injury to the temporalis and medial pterygoid muscles causing trismus. – Amphetamines and phenothiazines are thought to cause motor disturbances of the trigeminal nerve and spasm of masticatory muscles leading to bruxism and possible trismus.

PREVENTATIVE MEASURES

• In patients with a known history or family history of MH, avoid triggering agents such as succinylcholine and volatile agents. Use of a total IV anesthetic or regional technique should be utilized. • Carefully assess for a difficult airway with preexisting trismus – A mouth opening <3 finger breaths or 20 mm is considered significant. • Treatment for preoperative trismus includes NSAIDS, muscle relaxants, heat, exercises, and range of motion devices.

PREOPERATIVE ASSESSMENT • The inability to open the mouth despite an abolition of twitches after neuromuscular relaxation is administered. • MH; signs include trismus, total body rigidity, tachycardia, mixed respiratory and metabolic acidosis, hypercarbia (early sign), increased temperature (late sign), and myoglobinuria.

DIFFERENTIAL DIAGNOSIS

• Masseter muscle rigidity (MMR) describes difficulty with opening the mouth, but not the complete inability. • Inadequate depth of anesthesia or neuromuscular relaxation • Neuroleptic malignant syndrome • Etomidate myoclonus

TREATMENT

• Trismus after induction – Bag mask ventilation possible Asleep nasal or oral fiberoptic intubation Light wand Retrograde wire-assisted intubation Awaken patient – Bag mask ventilation difficult/impossible Blind nasal intubation Awaken patient and perform a nasal or oral fiberoptic intubation. Surgical airway • Pre-existing trismus – Bag mask ventilation appears possible Awake or asleep nasal or oral fiberoptic intubation Advanced airway technique after induction: Light wand, retrograde wire-assisted intubation – Bag mask ventilation appears difficult/impossible Awake nasal or oral fiberoptic intubation Surgical airway • If patient appears “light,” resulting in an inability to open the mouth, increase the depth of anesthetic. • If MH is suspected, discontinue the surgery and anesthetic. – If an emergency case, change anesthetic to nontriggering MH agents and monitor for signs of MH. – MH treatment Discontinue triggering agents (volatile agent) Hyperventilate, with 100% oxygen at high flow Start dantrolene at 2.5 mg/kg, repeat every 5 minutes until symptoms improve or up to 10 mg/kg (maximum dose may need to be exceeded in some cases). Consider continuing dantrolene at 1 mg/kg for up to 24 hours Send arterial blood gases and treat metabolic acidosis with bicarbonate 1–2 mEq/kg to maintain pH Monitor CK, electrolytes, and myoglobin until normalized. Check hepatic function Consider placing arterial or central venous line Treat hyperkalemia with calcium, glucose/insulin, and bicarbonate. Maintain adequate urine output with hydration and consider mannitol for renal protection Cool patient’s core body temperature to 37–39°C

FOLLOW-UP • If trismus is the result of pre-existing conditions, consider labeling the patient as a “Difficult Airway.” • If MH is suspected, admit the patient for 24 hours to monitor for manifestations. Discuss workup (caffeine test, muscle biopsy).

REFERENCES

1. Glahn KPE, Ellis FR, Halsall PJ, et al. Recognizing and managing a malignant hyperthermia crisis: Guidelines from the European Malignant Hyperthermia Group. Br J Anaesth. 2010;105(4):417–420. 2. Litman RS, Rosenberg H. Malignant hyperthermia. JAMA. 2005;293(23):2918–2924.

3. Rosenburg H. Trismus is not trivial. Anesthesiology. 1987;67(4):453–455. 4. Schwartz L, Rockoff MA, Koka BV. Masseter spasm with anesthesia. Anesthesiology. 1984;61(6):772–775.

5. Shulman DH, Shipman B, Willis FB. Treating trismus with dynamic splinting: A cohort case report. Adv Ther. 2008;25(1):9–16. 6. Van der Spek AF, Fang WB, Ashton-Miller JA, et al. The effects of succinylcholine on mouth opening. Anesthesiology. 1987;67(4):459–465. See Also (Topic, Algorithm, Electronic Media Element)

• Malignant hyperthermia • Difficult airway

CODES ICD9 • 771.3 Tetanus neonatorum • 781.0 Abnormal involuntary movements ICD10 • A33 Tetanus neonatorum • R25.2 Cramp and spasm

CLINICAL PEARLS

• If trismus presents after induction, the decision to proceed with the surgery depends on the surgical procedure, urgency of the case, and ability for postoperative care (ambulatory center versus hospital). • An airway exam prior to induction may identify patients with risk factors for trismus. Be prepared to manage their airway with alternate devices or techniques.

TURP SYNDROME Daniel Cormican, MD Jay A. Roskoph, MD, MBA

BASICS DESCRIPTION

• Transurethral resection of the prostate (TURP) is a common urologic procedure to help alleviate the urinary obstructive symptoms of benign prostatic hypertrophy (BPH) (1). This endoscopic procedure utilizes irrigation solution to aid with visibility; it distends structures and clears tissue debris and blood. However, the exposed prostate vasculature can absorb irrigant fluids, resulting in systemic absorption. • TURP syndrome is an iatrogenic constellation of signs and symptoms caused by volume overload, hyponatremia (serum sodium <125 mEq/L), and osmolality and solute aberrations. TURP syndrome can – Produce deleterious effects on central nervous, cardiovascular, metabolic, and renal systems. – Be potentially fatal if not recognized and treated appropriately. • The anesthetic plan for a TURP procedure may consist of either a general or neuraxial technique, while maintaining a high index of suspicion for TURP syndrome if signs and symptoms arise. Cardiac morbidity and mortality is equivocal when comparing general and neuraxial anesthesia. EPIDEMIOLOGY Prevalence

• 0.78–1.4% of all TURP procedures • Alternative treatments for BPH have resulted in a decreased number of procedures and hence occurrence. Morbidity

• Varies depending on the severity of the syndrome • In general, patients with significant comorbidities are at a greater risk for morbidity associated with TURP Syndrome. Mortality

Can reach up to 25% in severe TURP syndrome (defined as symptoms of TURP syndrome plus hyponatremia <120 mEq/L) (2). ETIOLOGY/RISK FACTORS

• Resection of the prostatic urethra and prostate gland nodule is completed using a resectoscope equipped with electrocautery capability. An irrigation solution is used to maintain visibility for the surgeon. Systemic absorption of the irrigant leads to TURP

syndrome. • A variety of factors are associated with an increased risk of TURP syndrome – Position: Increased with Trendelenburg position, as gravity facilitates absorption. – Prostate size: Gland size >45 g; larger glands often increase vascular exposure to irrigation solutions – Procedure time: Gland resection time >90 minutes; longer procedure times increase exposure to irrigation solutions – Surgical hemostasis/visibility: Impaired visibility of the surgical field requires the use of more irrigation. Decreased visibility may also increase surgical times; this results in increased exposure time of irrigation solution to the open vasculature. – Irrigant fluid bag height: (controversial) There are reports that a fluid bag height >60 cm above the patient creates high irrigation pressures, which increases risk (2,3).

PHYSIOLOGY/PATHOPHYSIOLOGY

• The prostate is made up of four zones contained within one capsule. The gland has a rich vascular supply within and immediately adjacent to the gland. – Irrigation solution gains immediate access to the circulation via openings in the prostate capsule during resection procedures, or over time as irrigant solution is taken up from retroperitoneal and/or perivesicular spaces. Among other concerns, irrigation solutions are ideally transparent, nonhemolytic, isotonic, nonconductive, and inexpensive. Glycine solution: Glycine itself may lead to hyperglycinemia, which is associated with encephalopathy, seizures, and visual disturbances. Glycine is known to increase NMDA receptor activity, which may then increase CNS excitation. Liver and kidney metabolism of intravascular glycine creates glycolic acid and ammonia, both of which are potentially toxic. Cytal solution: Can create increased levels of fructose, which is poorly handled by those with liver dysfunction. Physiologic saline, sorbitol, and mannitol have also been described for use in TURP. • Intravascular volume expansion: Large volumes of irrigant solution can be moved into the intravascular circulation; this is enhanced with large volume irrigation and lengthy procedures. This volume increase is poorly tolerated in patients with renal disease or poor left ventricular function (1,2). • Hyponatremia: Acute hyponatremia can develop due to the rapid uptake of irrigation solutions. These changes in serum sodium are poorly tolerated (especially by the CNS). Hyponatremia causes intracellular edema within neurons, which alters normal neuronal function. The relative decrease in serum sodium is important, but the symptomatic patient with a serum sodium <120 mEq/dL defines severe TURP Syndrome. • Hypoosmolality: Often associated with hyponatremia; acute hypoosmolality causes changes in neuronal transmembrane potentials. Such changes can lead to CNS abnormalities, due to cerebral edema and altered neuronal transmission.

PREVENTATIVE MEASURES

• Avoid the steep Trendelenburg position • Surgical efficiency promotes shorter procedure times and less volume of irrigant solution used.

• Maintain the irrigant solution bag at a height <60 cm above the level of the patient. • If concern for TURP syndrome arises, discussion with the surgeon should occur. Consideration should be given to checking serum sodium, which would assist in early diagnosis of hyponatremia. • Some surgeons may ask for prophylactic furosemide; this should be done with careful consideration of volume status and serum sodium; attention must be paid to furosemide side effects (hypotension, electrolyte imbalances). • Consider other BPH treatment options in patients with very large prostate glands and significant comorbidities. • Spinal or epidural anesthesia may be preferable to general anesthesia as TURP syndrome symptoms may be identified earlier in responsive patients. • Minimize maintenance fluids and boluses. Consider low-dose phenylephrine infusion preceding a neuraxial technique to avoid hypotension, in lieu of fluid boluses. • Newer TURP procedures (e.g., TURP with GreenLight laser) allow for use of saline irrigation, which may reduce incidence of TURP syndrome.

PREOPERATIVE ASSESSMENT • TURP Syndrome is a clinical diagnosis based on identification of signs and symptoms, which are often vague. A high index of suspicion on the part of the anaesthetist and urologist is thus essential. Signs, symptoms, and laboratory findings include – Neurologic: Agitation or lethargy, confusion and restlessness, which may progress to seizures, paralysis, and coma. Nausea and vomiting may be seen, as may visual disturbances. – Cardiovascular: Hypertension and bradycardia or dysrhythmia may be seen as early findings. Respiratory distress, hypotension, and frank shock may follow. – Metabolic/renal: Hyponatremia, hypoosmolality, hyperglycinemia, hyperammonemia, and acute renal failure may be noted on laboratory evaluation. • Severe TURP syndrome is commonly defined as a symptomatic patient with a serum sodium <120 mEq/L.

DIFFERENTIAL DIAGNOSIS

• Cerebrovascular accident • Acute renal failure • Postoperative delirium • Acute coronary syndrome or cardiogenic shock

TREATMENT • Mild symptoms: First symptoms are often nausea and face/neck paresthesias; the first signs may be bradycardia and decreased BP. Initial treatment should be directed at symptoms (e.g., treat nausea with antiemetics). Consider close monitoring and review of laboratory data. • Severe symptoms

– Hypertension and/or bradycardia may require invasive monitoring (arterial line or central line), atropine, or inotropes. If believed to be due to hypervolemia, volume removal may be necessary. Furosemide treatment, beginning at a low dose (20 mg IV), helps reduce free water volume; however its use is suggested only in the setting of hypervolemia, as hyponatremia may worsen. Additional doses can be titrated as needed. Hemodialysis for volume removal has a role as well, especially in patients with ESRD that are unable to create urine or clear toxins (like glycine or ammonia). – Severe hyponatremia may require hypertonic saline administration, with the goal to slowly raise the serum sodium over several hours. It is recommended that the serum sodium be increased at a rate of ∼0.5 mEq/hour. If corrected too fast, central pontine myelinolysis (CPM) may result. CPM occurs with rapid neuronal cellular volume decrease secondary to rapid correction of hyponatremia; symptoms occur 2–6 days after sodium correction, and can include dysphagia, dysarthria, muscle weakness/paralysis, and obtundation; may be irreversible. – Seizures may be halted with barbiturates, benzodiazepines, or propofol. The use of barbiturates or propofol may impair ventilation and airway protection Serum magnesium levels may also be altered during TURP syndrome and a magnesium (Mg2+) infusion trial (an NMDA antagonist) may stop seizures, especially in the setting of hyperglycinemia (1,2). Mg2+ can be given as 2 g over 10 minutes while watching for toxicity (muscle weakness, mental status changes, pulmonary edema). – Cardiovascular collapse requires ACLS with mechanical ventilation as necessary. • Consider consultation of appropriate medical specialists (e.g., nephrologists for fluid and electrolyte evaluation, neurologists for neurologic status evaluation).

FOLLOW-UP ICU care as required by patient status and monitoring needs.

REFERENCES

1. Gravenstein D. Transuretheral resection of the prostate (TURP) syndrome: A review of the pathophysiology and management. Anesth Analg. 1997;84:438–446. 2. Hawary A, Mukhtar K, Sinclair A, et al. Transuretheral resection of the prostate syndrome: Almost gone but not forgotten. J Endourol. 2009;23:2013–2020. 3. Malhotra V. Transurethral resection of the prostate. Anesthesiol Clin North Am. 2000;18:883–897.

ADDITIONAL READING

• Adrogue HJ, Madias NE. Hyponatremia. N Eng J Med. 2000;342:1581–1589.

See Also (Topic, Algorithm, Electronic Media Element) • Hyponatremia • Epidural

• Spinal

CODES ICD9

• 276.1 Hyposmolality and/or hyponatremia • 997.5 Urinary complications, not elsewhere classified ICD10

• E87.1 Hypo-osmolality and hyponatremia • N99.89 Oth postprocedural complications and disorders of GU sys

CLINICAL PEARLS

• A high index of suspicion is crucial so that the condition can be treated in its earliest stage. A high level of monitoring and supportive care should be immediately instituted. If untreated, it may progress to death. • Signs and symptoms of TURP syndrome can be vague and seemingly unrelated. The pathophysiologic basis is – Acute volume overload – Dilutional hyponatremia – Osmolality/solute aberrations.

ULCERATIVE COLITIS Andrea Parsons, MD

BASICS DESCRIPTION

• Ulcerative colitis is an inflammatory bowel disease that is characterized by inflammation leading to ulcers in the large intestine. It usually involves the rectum and may extend more proximally to involve the colon. • Patients present in the perioperative period for colectomies (curative), ileostomy-related procedures, or management of non-related problems. EPIDEMIOLOGY Incidence

• US: 2–14 cases per 100,000 (1) • Bimodal distribution with diagnosis peaking between ages 15 and 25 and then in the 50s

Prevalence

More common in females (2)

Morbidity

• The ultimate cure is colectomy • Patients suffer from flare-ups that can cause significant discomfort and weight loss.

Mortality

Low, but there is an increased rate of colorectal cancers. ETIOLOGY/RISK FACTORS

• The exact cause of ulcerative colitis (UC) is unknown, but immune system abnormalities and environmental factors have all been postulated as causes of UC (3). • There is a genetic predisposition as evidenced by familial and twin studies. PATHOPHYSIOLOGY

• UC is an inflammatory bowel disease that leads to cell necrosis and the development of ulcers. These ulcers bleed and produce pus. • Cause: Evidence suggests that normal intestinal flora can trigger an aggressive and inappropriate immune reaction in patients with a multifactorial genetic predisposition. No specific environmental, dietary, or infectious causes have been identified. • Inflammation is often confined to the mucosa of the colon and rectum; whereas in Crohn’s disease, it is transmural. Additionally, with UC there is continuous, adjacent involvement; whereas in Crohn’s disease, it is patchy and cobble-stoned. – Cytokine release includes interleukin-1 (IL-1) which causes diarrhea and acts as a pyrogen.

Other cytokines released include IL-6, IL-8, and tumor necrosis factor-α (TNF-α). – Neutrophils and mononuclear cells are believed to cause cryptitis and crypt abscesses. – Cytokines lead to differentiation of lymphocytes to T cells (mainly Helper T cells Type 2), leading to immune system activation, inflammatory response, and subsequent damage of the intestinal mucosa. • Diarrhea and pain can cause electrolyte abnormalities and malnutrition. • Anemia occurs due to blood loss (acute or chronic) and due to malabsorption of iron, vitamin B12, and folate. • Diagnosis can be made with a biopsy of affected tissue via endoscopy. • Imaging with plain films and CT scan can aid in diagnosis, especially diagnosing complications such as toxic megacolon

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess the severity of the disease and concomitant organ dysfunction. • Anesthetic plan should focus on fluid and electrolyte management, assessment of anemia, and use of steroids.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Exacerbations consist of diarrhea with blood and mucus, abdominal cramping, bloating, acute pain, weakness, rectal bleeding, fevers, weight loss, pain in the lower left abdomen. • Toxic megacolon can occur in severe cases when impaired colonic motility is present. This can lead to perforation.

History

• Severity of chronic condition • Recent acute flares • Co-morbidities and complications of therapy such as diabetes and hypertension from chronic steroid use.

Signs/Physical Exam

• Signs of dehydration: Decreased skin turgor, capillary refill, urinary output, blood pressure as well as tachycardia • Signs of electrolyte abnormalities: Muscle weakness • Malnutrition and vitamin deficiencies • Painful lower extremity swelling may indicate a deep venous thrombosis (increased risk); shortness of breath may indicate a pulmonary embolus

TREATMENT HISTORY

• Surgical resection of the colon is a treatment option for severe disease and for toxic megacolon unresponsive to medical treatment. • Total parenteral nutrition (TPN)

MEDICATIONS

• Antiinflammatories: Maintenance therapy includes 5-aminosalicylic acid, steroids (prednisone), and immunomodulators such as azathioprine, cyclosporin, and infliximab for refractory disease (4). • Diagnosis is via biopsy of affected tissue on sigmoidoscopy/colonoscopy. Imaging with plain films and CT scan can also aid with diagnosis, especially complications such as toxic megacolon. DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Complete blood count to assess for anemia and hemoconcentration • Complete metabolic panel (electrolytes and LFTs). BUN/Cr ratio of 20:1 may indicate dehydration, and low bicarbonate values may indicate acidosis due to dehydration or infection. • Coagulation studies if liver disease is present • EKG • Type and screen or type and cross if anemia is present

CONCOMITANT ORGAN DYSFUNCTION Extra-intestinal manifestations:

• Eye: Episcleritis, uveitis, dry eyes • Liver: Jaundice, fluid retention, primary sclerosing cholangitis • Bone: Arthritis, including ankylosing spondylitis, can result in reduced flexibility, joint pain, and reduce mobility. Metabolic bone disease can occur from chronic electrolyte abnormalities and poor absorption of nutrients. • Hematologic: Autoimmune hemolytic anemia • Skin: Erythema nodosum (tender, red nodules that appear over the shins and ankles as well as the arms) and pyoderma gangrenosum (necrosis of skin leading to large ulcers) CIRCUMSTANCES TO DELAY/CONDITIONS

• Significant hypovolemia and/or electrolyte disturbances • Severe anemia requiring blood transfusion

CLASSIFICATIONS

• Based on severity – Mild – Moderate – Severe • Based on the extent of colonic involvement – Proctitis (involvement of rectum only) – Proctosigmoiditis (involvement of the rectum and sigmoid colon) – Left-sided colitis (involvement of the rectum and colon up to the splenic flexure) – Pancolitis (involvement of the entire colon)

TREATMENT

PREOPERATIVE PREPARATION Premedications

• Anxiolysis as needed • Stress dose steroids should be considered if the patient has been treated for more than 2 weeks within the past 6–12 months to avoid manifestations of adrenal insufficiency. Steroids with glucocorticoid and mineralocorticoid activity should be administered.

INTRAOPERATIVE CARE Choice of Anesthesia

• Epidurals for intraoperative (with or without GA) and postoperative management should be considered for abdominal procedures. However, neuraxial blocks may be precluded with coagulopathy.

Monitors

• Standard ASA monitors • Avoid rectal temperature monitoring • Foley catheter in long cases, suspected hypovolemia, or anticipated large fluid shifts • Arterial line may be considered in patients who are anemic, have baseline electrolyte abnormalities, brittle diabetes (from steroid use), or if the surgical procedure is anticipated to yield large blood loss. • Consider a central venous catheter for pressure monitoring and guidance on fluid resuscitation.

Induction/Airway Management

• In hypovolemic patients, consider adequate preoperative fluid hydration prior to induction. • Etomidate or ketamine can be useful in hypovolemic patients; have vasopressors available. • In anemic patients, consider having blood available or transfuse prior to induction.

Maintenance

• Muscle relaxation can aid surgical exposure and closure of abdominal fascia for bowel surgery. • Fluid management: Replace deficits with crystalloid. Be aware of and replete insensible losses. Patients are at risk for significant third-spacing and bowel edema, especially due to low colloid oncotic pressures. This can make closure of abdominal incisions more difficult. • Low albumin levels due to malnutrition: Adjust medication doses appropriately, particularly with highly protein-bound drugs. Unbound, free drug is pharmacologically active, and is also available for metabolism. Thus consider smaller boluses and more frequent dosing. Additionally, hypoalbuminemia may result in increased total body water and volume of distribution for hydrophilic drugs. • Consider avoiding nitrous oxide for bowel surgery as it can cause the bowel to expand and make fascial closure more difficult. • Diabetics may require intraoperative glucose management with insulin. • Intractable intraoperative hypotension may be due to adrenal insufficiency; treat with stress dose steroids.

• Eye protection to avoid worsening ocular manifestations • Skin may be thin or easily breached from long-term steroid use; caution with positioning and tape for IV sites, ETT, and eyes

Extubation/Emergence

Reversal of nondepolarizing muscle relaxants can help minimize weakness as patients often have underlying weakness due to malnutrition and electrolyte disturbances.

POSTOPERATIVE CARE BED ACUITY

Telemetry if the patient has severe electrolyte derangements MEDICATIONS/LAB STUDIES/CONSULTS

• Consider an epidural or PCA for post-operative pain control with large incisions for colectomy. • Avoid ketorolac and non-steroidal anti-inflammatory drugs due to metabolic bone disease. • Postoperative complete blood count (CBC).

COMPLICATIONS

• Weakness, cardiac arrhythmias, hypo/hyperglycemia • Complications due to hyperalimentation include hypo/hyperglycemia, hyperchloremic metabolic acidosis, fluid overload, electrolyte abnormalities, renal and hepatic dysfunction

REFERENCES

1. Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology. 2004;126(6):1504–1517. 2. Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007;5(12):1424–1429. 3. Abraham C, Cho JH. Inflammatory bowel disease. N Eng J Med. 2009:361(21):2066–2078. 4. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007; 369(9573):1627–1640.

ADDITIONAL READING

• Kornbluth A, Sachar DB, Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105(3):501– 523. • National Digestive Diseases Information Clearinghouse

See Also (Topic, Algorithm, Electronic Media Element) • Crohn’s disease

• Epidural

CODES ICD9

• 556.8 Other ulcerative colitis • 556.9 Ulcerative colitis, unspecified ICD10

• K51.90 Ulcerative colitis, unspecified, without complications • K51.919 Ulcerative colitis, unsp with unspecified complications

CLINICAL PEARLS

• Assess fluid status and electrolytes and resuscitate as indicated. • UC can cause weakness due to electrolyte abnormalities and malnutrition. • Patients often present for colectomy, proctectomy, wound biopsy, incision/drainage, irrigation and debridement; urgent surgery for actual or impending perforation.

ULNAR NEUROPATHY Jane C. Ahn, MD Sharon L. Lin, MD

BASICS DESCRIPTION

• The ulnar nerve is formed by the C8 and T1 nerve roots and travels as part of the medial cord of the brachial plexus. • Ulnar injury is most common at the elbow, where the nerve is exposed and vulnerable as it traverses superficially in the ulnar groove. Prolonged pressure at the elbow during surgery may result in compression and ischemia of the ulnar nerve. • Ulnar nerve injury is the most common postoperative nerve injury. However, there is no direct evidence that positioning or padding alone can prevent perioperative ulnar neuropathies due to the multifactorial etiology. • Injury to the ulnar nerve may result in sensory or motor disturbances as well as pain in the distribution of the nerve. Presentation is variable: – Symptoms: Pain, numbness, and tingling present most commonly – Severity: Mild to severe – Onset: Immediate to delayed (several days after surgery) – Resolution: Spontaneous to persistent (lasting longer than 3 months) EPIDEMIOLOGY Incidence

• Persistent ulnar neuropathy in non-cardiac surgery patients: 0.04%–0.5% (1,2). • Cardiac surgery patients: 1.5%–24%, secondary to injury from median sternotomy (3). • Male:female ratio of 3:1; which may be due to anatomic differences of the elbow. In males, the tubercle of the coronoid process at the elbow is larger and has less fat around the medial aspect (1). • Medical and surgical patients: Occurs in equal frequency when hospitalized for more than 2 days (3).

Morbidity/Mortality

• Prognosis depends on the preservation of the ulnar nerve axon. – Neurapraxia (damage to myelin sheath but preservation of the axon) is more likely to resolve. – Axonal injury results in slower recovery and can have incomplete resolution. ETIOLOGY/RISK FACTORS

• Exact mechanism is often unknown, but improper positioning or padding during surgery is often implicated. • Ulnar nerve damage can occur through:

– Compression and stretch – Ischemia – Metabolic derangements – Direct trauma or laceration • Independent risk factors: – Male gender – Prolonged hospitalization greater than 14 days – Extreme body habitus (BMI <24 or ≥38) • Other associated factors: – Pre-existing subclinical neurologic dysfunction (e.g., diabetes mellitus, severe peripheral vascular disease, use of neurotoxic chemotherapy) – Increasing age – Use of general anesthesia – Prolonged hypotension – Local anesthetic toxicity – Manipulation of the brachial plexus during surgery – Compressive dressings/casts – Tourniquet inflation – Hematoma or abscess formation – Stretch or compression during surgical positioning

PHYSIOLOGY/PATHOPHYSIOLOGY

• The ulnar nerve comprises motor and sensory fibers from the C8 and T1 nerve roots. Before entering the axilla, the ulnar nerve separates from the brachial plexus after the medial cord divides into the ulnar nerve, median nerve, and medial cutaneous nerves of the arm and forearm. The ulnar nerve travels through the upper arm, elbow, forearm and digits and can be damaged at any point in its course. • Cubital tunnel: The most common area of injury due to the superficial location of the nerve. – The cubital tunnel retinaculum (CTR) forms the roof of the cubital tunnel and connects the medial epicondyle and olecranon at the elbow. – Flexion tightens the CTR overlying the ulnar nerve and persistent compression can lead to damage. – Women have a higher fat content on the medial side of the elbow which may be protective against developing an ulnar neuropathy. • Proximal forearm: The ulnar nerve travels superficially in the proximal forearm making it vulnerable to compression by the coronoid process of the ulna. – The coronoid process is more pronounced in men compared to women, which may contribute to the higher incidence of ulnar neuropathy in men. • Guyon’s canal at the wrist: Second most common area of injury. The sensory branches of the ulnar nerve are prone to compression. • Double-crush syndrome may occur when a pre-existing, even subclinical, nerve injury is more likely to incur damage if a second injury occurs.

PREVENTATIVE MEASURES

• ASA Practice Advisory Committee recommends the following positioning precautions: (4)

– Arm abduction limited to ≤90% in supine position – Arms should be positioned to decrease pressure on the ulnar groove – Use neutral forearm position when tucking arms – Always use padded arm boards • The ASRA Practice Advisory Committee recommends the following for regional anesthesia: (5) – Consider modifying the regional technique in patients with pre-existing clinical or suspected sub-clinical peripheral nerve injury (reduce dose, concentration, or potency of local anesthetic and reduce vasoconstrictive additives). – Avoid placement of regional blocks in adults under general anesthesia or heavy sedation except in circumstances when the physician and the patient agree that the benefit outweighs the risks.

DIAGNOSIS • History: Risk factors, onset • Symptoms: Paresthesia, pain, and numbness along the medial portion of the palm and 4th and 5th digits. • Physical Exam: Reduced sensation, atrophy of the hypothenar eminence, weakness of the interossei muscles, “claw hand” deformity (seen in severe cases) of the 4th and 5th digits. Exam should be carefully documented. • Studies – Nerve conduction velocity testing (NCV) and electromyography (EMG) may identify the location of neural insult. However, because neurophysiologic changes are most apparent 14–21 days after injury, earlier testing with NCV and EMG may be helpful for establishing a baseline and aiding in prognosis. – CT or X-ray to look for bone or joint abnormalities responsible for compression.

DIFFERENTIAL DIAGNOSIS • Brachial plexopathy • Carpal tunnel syndrome • Median nerve neuropathy • Radial nerve neuropathy

TREATMENT • No therapeutic procedure has been proven to consistently improve symptoms of ulnar neuropathy. • If symptoms fail to progressively improve, neurological consultation should be sought in 2–3 weeks. • Complete absence of nerve function or the progression of neurologic deficits should prompt urgent evaluation by a neurologist or orthopedic hand surgeon. – Cubital tunnel decompression or reconstructive nerve repair may or may not be useful in select cases.

FOLLOW-UP After the initial neurological evaluation, incomplete and unresolved lesions should be followed up in 3–5 months. CLOSED CLAIMS DATA

• Approximately 28% of all nerve injury claims in the ASA Closed Claims Study involved ulnar neuropathy (including all general anesthesia, regional, MAC cases) (6). • 85% of ulnar nerve injury claims are associated with general anesthesia (6). • 27% of cases related to ulnar nerve injury specifically state that extra padding was used at the elbows (6). • Permanent ulnar nerve damage resulted from 4% of total peripheral nerve block claims (134 peripheral nerve block claims out of 1,005 regional anesthesia claims) (7). • Anesthesia care judged appropriate in 73% of ulnar nerve injury cases (6). • Frequency of payment was 47% in ulnar nerve injury cases where care was deemed appropriate and median payment was $35,600 (6).

REFERENCES

1. Warner MA, Warner ME, Martin JT. Ulnar neuropathy: Incidence, outcome, and risk factors in sedated or anesthetized patients. Anesthesiology. 1994;81:1332–1340. 2. Warner MA, Warner DO, Matsumoto JY, et al. Ulnar neuropathy in surgical patients. Anesthesiology. 1999;90:54–59. 3. Prielipp RC, Morrell RC, Butterworth J. Ulnar nerve injury and perioperative positioning. Anesthesiol Clin N Am. 2002;20(3):589–603. 4. Practice advisory for the prevention of perioperative peripheral neuropathies. A report by the ASA Task Force on prevention of perioperative peripheral neuropathies. Anesthesiology. 2000;92:1168–1182. 5. Neal JM, Bernards CM, Hadzic A, et al. ASRA Practice Advisory on neurologic complications in regional anesthesia and pain medicine. Reg Anesth Pain Med. 2008;33(5):404–415. 6. Cheney FW, Domino KB, Caplan RA, et al. Nerve injury associated with anesthesia: A Closed Claims Analysis. Anesthesiology. 1999;90:1062–1069. 7. Lee LA, Posner KL, Domino KB, et al. Injuries associated with regional anesthesia in the 1980s and 1990s: A closed claims analysis. Anesthesiology. 2004;101:143–152.

ADDITIONAL READING • Corneal abrasions

CODES ICD9

354.2 Lesion of ulnar nerve ICD10 • G56.20 Lesion of ulnar nerve, unspecified upper limb • G56.21 Lesion of ulnar nerve, right upper limb • G56.22 Lesion of ulnar nerve, left upper limb

CLINICAL PEARLS

• Ulnar neuropathy has been shown to occur in equal frequency in medical patients hospitalized and on prolonged bed rest in the supine position. Hospitalized patients commonly flex their elbows and rest their hands on the upper abdomen or chest. This position increases external compression, stretch and pressure on the ulnar nerve. • The cause of ulnar neuropathy is often unknown; however, extra vigilance with positioning and padding may help prevent some cases, particularly in patients with identifiable risk factors. • Carefully document all precautions taken to protect the ulnar nerves. In the event of an injury, careful follow-up, coordination of care and documentation are critical.

UMBILICAL CORD PROLAPSE Natesan Manimekalai, MD

BASICS DESCRIPTION

• Umbilical cord prolapse into the cervical canal, adjacent to or in front of a fetal presenting part, can lead to cord compression and fetal asphyxia. It occurs most commonly during or after membrane rupture. • A prolapsed cord is an obstetric emergency; delay in management is associated with a significant increase in neonatal morbidity and mortality. EPIDEMIOLOGY Incidence

• Overall incidence: ∼0.4% • Breach presentation: ∼1%

Morbidity

• Fetal morbidity is associated with asphyxiation, and can result in motor and cognitive deficits. • Maternal morbidity is associated with emergent Cesarean delivery: Pain, endometritis, bowel/bladder injury, and/or hemorrhage. Mortality

Fetal mortality: ∼15%. The rate has significantly decreased within the past 2 decades due to advancements in Cesarean delivery techniques, in utero resuscitation, and neonatal intensive care units. ETIOLOGY/RISK FACTORS

• Premature rupture of membranes (1) • Breech presentation • Long umbilical cord • Fetal prematurity • Uterine distention: Polyhydramnios, multiple gestations, multiparity • Obstetric interventions: Artificial rupture of membranes, external cephalic version, internal podalic version of the second twin, placement of an intrauterine pressure catheter. PHYSIOLOGY/PATHOPHYSIOLOGY

• Prolapse of the umbilical cord in front of the fetal presenting part leads to a reduction or cessation of fetal blood flow. With contractions, there is further compromise of fetoplacental perfusion. • Exposure of the umbilical cord to the lower temperature outside the uterus causes

vasospasm of the umbilical arteries and an additional decrease in fetal oxygen supply. • Fetal hypoxia manifests as severe, variable decelerations and profound fetal bradycardia. • Fetal death follows if the cord compression is not relieved immediately.

PREVENTATIVE MEASURES

• Obstetrical concerns: – Artificial rupture of membranes should be performed with caution if the fetal presenting part is not engaged. – In utero resuscitative measures may help reduce further cord compression and improve outcome. • Joint obstetric and anesthesia concerns: – In the presence of cord presentation, emergent Cesarean section should be performed. – The Joint Commission on Accreditation of Healthcare Organizations recommends that labor and delivery units regularly conduct simulated emergency Cesarean section procedures and debrief the entire team after the simulation. Emergency Cesarean section simulation drills and standardization of procedures for Cesarean deliveries appear to reduce the decision-to-delivery time and improve both fetal and maternal outcome (2).

DIAGNOSIS Made by the obstetrics team • Cervical exam: Umbilical cord visible or palpable in the vagina or at the vulva. • Fetal heart tracing: Variable decelerations, fetal bradycardia • In high-risk women, intra-partum ultrasound scan or color Doppler can be diagnostic prior to amniotomy.

TREATMENT • In utero resuscitative measures – Once cord prolapse is recognized, management focuses on immediate delivery. Cervical dilatation and fetal condition are rapidly assessed. The fetus may be delivered vaginally if cervical dilation is complete and delivery is imminent. Cesarean delivery is indicated if vaginal delivery is not imminent. – While preparing for Cesarean delivery, the obstetric team will make attempts to relieve pressure on the umbilical cord. This is performed by: Manually elevating the presenting fetal part away from the umbilical cord Positioning the parturient in the Trendelenburg, left lateral decubitus, or knee–chest position to reduce the pressure on the umbilical cord Inserting urinary catheter and distending the bladder with ∼500 mL of saline to elevate the presenting part and reduce cord compression Minimizing the handling of the cord Covering the portion lying outside the vagina with warm packs to prevent vasospasm Using tocolysis to halt uterine contractions • Pre-anesthetic preparation

– Establish intravenous access and initiate a rapid fluid bolus. – Assess the airway – High-flow oxygen via non-rebreathing mask to supplement oxygen delivery to the fetus. Conversely, if a general anesthetic is going to be performed, preoxygenate the patient. – Check the cord pulsation – Anti-aspiration precautions should be made with sodium bicitra, metoclopramide, and/or H2-blockers.

• General anesthesia is indicated if neuraxial analgesia is not already established and there is evidence of fetal distress. – Rapid sequence induction with cricoid pressure following sterile preparation and draping of the abdomen. – Hyperventilation should be avoided because it may reduce uteroplacental blood flow. – Prior to the delivery of the fetus, anesthesia is maintained with inhalation agent at 1 MAC. – Following delivery, inhalation agents are reduced to <0.5 MAC to minimize uterine relaxation. – An orogastric tube is placed to empty the stomach prior to extubation. – Extubate when awake and alert to prevent gastric aspiration. • Neuraxial anesthesia is preferred in the setting of increased maternal risk associated with general anesthesia (e.g., difficult airway). – In the presence of a pre-existing epidural, surgical anesthesia can be accomplished in 3 minutes with a 20 mL bolus of 3% chloroprocaine. – Spinal anesthesia can be performed in the head down, lateral decubitus, knee–chest position (3). Avoid the sitting position. Fetal heart tones should be continuously monitored during placement. • Neonatal resuscitation (4) – Neonates delivered after cord prolapse will invariably need resuscitation. The neonatal resuscitation team (NRT) should be present at the time of the delivery. It is important that health care providers other than those attending to the mother are available for neonatal resuscitation. – The initial steps in resuscitation are clearing of the airway, stimulation, and providing warmth. Evaluate respirations, heart rate, color, and muscle tone. – If the baby is apneic or gasping or if the heart rate remains <100 bpm, start positivepressure ventilation with bag-valve mask and/or endotracheal tube. Increased heart rate is indicative of effective ventilation. – Chest compressions are initiated if the heart rate is <60 bpm despite adequate ventilation for 30 seconds. Compressions to ventilations are performed at a rate of 3:1. – If the heart rate is <60 bpm despite adequate ventilation and chest compressions, administration of epinephrine may be indicated. The IV dose of epinephrine is 0.01–0.03 mg/kg per dose.

FOLLOW-UP • Patient-controlled analgesia for the post-partum mother • Local anesthetic infiltration

• Transverse abdominal plane block • Early ambulation • DVT prophylaxis

REFERENCES

1. Dilbaz B, Ozturkoglu E, et al. Risk factors and perinatal outcomes associated with umbilical cord prolapse. Arch Gynecol Obstet. 2006;274(2):104–107. 2. Siassakos D, et al. Retrospective cohort study of diagnosis-delivery interval with umbilical cord prolapse: the effect of team training. BJOG. 2009; 116(8):1089–1096.

3. Ginosar Y, et al. Emergency Cesarean delivery for umbilical cord prolapse: The head-down, knee-chest prone position for spinal anesthesia. Can J Anaesth. 2008;55(9):612–615.

4. Kleinman ME, et al. Pediatric basic and advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Pediatrics. 2010; 126(5):e1261–e1318. See Also (Topic, Algorithm, Electronic Media Element) • Epidural • Fetal heart tones

CODES ICD9 • 663.00 Prolapse of cord complicating labor and delivery, unspecified as to episode of care or not applicable • 762.4 Prolapsed umbilical cord affecting fetus or newborn ICD10 • O69.0XX0 Labor and delivery complicated by prolapse of cord, unsp • P02.4 Newborn (suspected to be) affected by prolapsed cord

CLINICAL PEARLS

• Umbilical cord prolapse is an obstetric emergency. • Risk factors include long umbilical cord, breech presentation, prematurity, uterine distention, and artificial or premature rupture of membranes. • Methods to temporarily minimize cord compression include manual reduction of the presenting part, knee–chest position, tocolysis, and bladder distention. • Emergency delivery is necessary to minimize fetal morbidity and mortality. • Emergency Cesarean section is a complex surgical procedure that requires effective communication among the multidisciplinary delivery team, including obstetricians, nurses, anaesthetist, pediatricians, and support personnel.

UPPER RESPIRATORY INFECTION, PREOPERATIVELY Elizabeth Rebello, MD

BASICS DESCRIPTION

• Children frequently present on the day of surgery with symptoms of an upper respiratory infection (URI). They have an increased risk of adverse respiratory that include: – Laryngospasm – Bronchospasm – Breath holding – Arterial oxygen desaturation • The question of whether to proceed or whether to cancel the case may be a source of debate. • The preoperative assessment should discern elements to optimize the anesthetic plan and to anticipate and limit any perioperative adverse respiratory events. EPIDEMIOLOGY Prevalence

Frequency of URI in children • Children under the age of 5 have, on average, 5–6 URIs per year (2). • Active symptoms may last 7–10 days. • Residual pulmonary effects remain for 2–6 weeks.

Prevalence

Not available Morbidity

• Risk of perioperative adverse events in children without an URI – One in every 5 children undergoing elective surgery has a mild intraoperative adverse event (3). – One in every ten has a postoperative adverse event (3). • Risk of perioperative adverse events in children with an URI: – Increased 7-fold in with an URI and 11-fold if the patient’s trachea was intubated (1) • Both groups have a low incidence of serious complications

ETIOLOGY/RISK FACTORS

• Risk factors for perioperative adverse events in children with an URI who present for surgery (4,5). – Viral nasopharyngitis accounts for 95% of URIs. Rhinovirus is the most common Other viruses include: Influenza, parainfluenza, coronavirus, respiratory syncytial virus – Copious secretions

– Tobacco smoke exposure – Snoring – Nasal congestion – Endotracheal tube in child <5 years of age – Prematurity (<37 weeks) – Surgery involving the airway – Reactive airway disease

PHYSIOLOGY/PATHOPHYSIOLOGY

• Airway reactivity can persist for up to 6 weeks after an infection. – Unclear mechanism which may involve neural mediation. – Viral neuraminidases may inhibit muscarinic receptors (6). – Inhibition results in an increase in acetylcholine and bronchoconstriction. • Changes in pulmonary physiology during viral infections: – Decreased forced vital capacity – Decreased functional residual capacity – Reduced diffusion capacity – Increased intrapulmonary shunting

PREVENTATIVE MEASURES

• Encourage parents to avoid pediatric exposure to environmental tobacco smoke – Children exposed to tobacco smoke had a 10-fold increase in the risk of laryngospasm (7).

PREOPERATIVE ASSESSMENT • Determine if any respiratory symptoms represent an infectious or non-infectious process as they may be similar – Infectious: Viral, bacterial – Non-infectious: Allergic • Viral cultures and lab tests – Lack sensitivity – May be impractical in a preoperative clinic setting or immediate preoperative setting • Clinical judgment and parental input – Most anaesthetists would cancel the case if it is elective and the child appears lethargic, febrile, with productive cough, purulent rhinitis, and rhonchi. Most would proceed with an elective case if the child has a mild to moderate URI that is stable. However, there is a wide spectrum of cases that fall between these categories for which clinical judgment on the part of the anaesthetist is based upon parental input and urgency of the case. There are no established practice guidelines – Parental feedback that the patient had a “cold” was a clinical predictor of anesthetic complications (5)[A]. DIFFERENTIAL DIAGNOSIS

• Upper respiratory tract infection: – Runny nose

– Congestion – Cough • Lower respiratory tract infection: – Wheezing – Crackles – Rales – Sputum production • Allergic process • Vasomotor

TREATMENT • If the decision is made to continue with the case, the goals for anesthetic management include: – Reduce secretions – Limit manipulation of a potentially sensitive airway – Suction airway under deep anesthesia (4,5)[A] • Choice of airway management. It should be noted that the incidence of adverse events is greater during the removal of the device compared to placement (8): – Endotracheal tube: Provides a more secure airway Has an increased risk for perioperative complications due to airway irritation and manipulation (1,5)[A]. – The laryngeal mask airway: May be an appropriate alternative Has a decreased risk of sore throat and postoperative nausea and vomiting (8)[C]. Is associated with a low incidence of adverse respiratory events. However, adverse events were increased when the URI was present within the last two weeks (9). • Preemptive bronchodilators and corticosteroids: In children with mild–moderate asthma, pretreatment reduced respiratory system resistance during intubation (10). • Lidocaine: May reduce airway hyperreactivity, but insufficient evidence exists to recommend routine use • Volatile agents: – Similar incidence of respiratory events with sevoflurane compared with halothane in a randomized study (11). – Lower perioperative events when sevoflurane was used to induce and maintain anesthesia as compared to induction with sevoflurane and maintenance with isoflurane (4).

FOLLOW-UP • If a case is rescheduled due to an URI, surgery should be delayed for at least 4 weeks following the URI (4). – For minor URIs, a 1–2 week delay may be sufficient. • Outcome studies have been equivocal.

CLOSED CLAIMS DATA

• Causes of perioperative pediatric cardiac arrest and death from the Pediatric Perioperative Cardiac Arrest Registry demonstrate that none were associated with an URI (12). • Data from closed claims studies for adults and children indicate that no cases were reported to have been associated with an URI (13,14).

REFERENCES

1. Cohen MM, Cameron CB. Should you cancel the operation when a child has an upper respiratory tract infection? Anesthesia and Analgesia. 1991:72:282–288.

2. Monto AS, Ullman BM. Acute respiratory illness in an American community. The Tecumseh study. JAMA. 1974;227:164–169.

3. Mamie C, Habre W, Delhumeu C, et al. Incidence and risk factors of perioperative adverse events in children undergoing elective surgery. Paediatri Anaesth. 2004;14:218–224. 4. Tait AR, Malviya S, Voepel-Lewis T, et al. Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections. Anesthesiology. 2001;95:299–306. 5. Parnis SJ, Barker DS. Clinical predictors of anesthetic complications in children with respiratory tract infections. Paediatr Anaesth. 2001;11:29–40. 6. Fryer A, El-Fakahany E, Jocoby D. Parainfluenza virus type 1 reduces the affinity of agonists for muscarinic receptors in guinea-pig lung and heart. Eur J Pharmacol. 1990;181:51–58. 7. Lakshmipathy N, Bokesch PM, Cowen DE, et al. Environmental tobacco smoke: A risk factor for pediatric laryngospasm. Anesth Analg. 1996;82:724–727. 8. Tait AR, Pandit OA, Voepel-Lewis T, et al. Use of the laryngeal mask airway in children with upper respiratory tract infections: A comparison with endotracheal intubation. Anesth Analg. 1998;86:706–711. 9. von Ungern-Sternberg BS, Boda K, Schwab C, et al. Laryngeal mask airway is associated with an increased incidence of adverse respiratory events in children with recent upper respiratory tract infections. Anesthesiology. 2007;107:714–719.

10. Silvanus MT, Groeben H, Peters J. Corticosteroids and inhaled salmeterol in patients with reversible airway obstruction markedly decrease the incidence of bronchospasm after tracheal intubation. Anesthesiology. 2004;100:1052–1057.

11. Rieger A, Schroter G, Philippi W, et al. A comparison of sevoflurane with halothane in outpatient adenotomy in children with mild upper respiratory tract infections. J Clin Anesth. 1996;8:188–197. 12. Mooray JP, Geiduschek JM, Ramamoorthy C, et al. Anesthesia-related cardiac arrest in children: Initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) Registry. Anesthesiology. 2000;93:6–14. 13. Morray JP, Geiduschek JM, Caplan RA, et al. A comparison of pediatric and adult closed malpractice claims. Anesthesiology. 1991;75:932–939. 14. Caplan RA, Posner KL, Ward RJ. Adverse respiratory events in anesthesia: A closed claims

analysis. Anesthesiology. 1990;72:828–833.

See Also (Topic, Algorithm, Electronic Media Element)

• Pediatric respiratory physiology • Laryngospasm

CODES ICD9

465.9 Acute upper respiratory infections of unspecified site ICD10

J06.9 Acute upper respiratory infection, unspecified

CLINICAL PEARLS

• The decision to proceed or cancel elective surgery for the child with an URI should be based on what is safest for that patient. • Children with uncomplicated minor respiratory infections may be managed safely. • Children with copious secretions, productive cough, purulent rhinitis, fever, and nasal congestion are at increased risk of perioperative adverse events. • Children exposed to tobacco smoke have an increased risk of laryngospasm. • A comprehensive preoperative assessment will help identify factors that predict outcome and guide the anesthetic plan for the child with a URI.

UREMIA

Rongjie Jiang, MB, MS Kirk H. Shelley, MD, PhD

BASICS DESCRIPTION

• Uremia, or urea in the blood, specifically describes the accumulation of toxins secondary to renal impairment. It does not encompass other commonly seen manifestations of renal disease such as derangements in extracellular volume, inorganic ion concentrations, or lack of known renal synthetic products. • Azotemia is the term used to describe increased urea levels without symptoms. • Uremic syndrome describes the conglomeration of symptoms that result from the accumulation of waste products that are normally cleared by the kidneys: – Anorexia – Nausea – Vomiting – Pruritus – Anemia – Fatigue – Coagulopathy • The impaired clearance of BUN is not the cause of all the above symptoms, but is nonetheless a good indicator of the severity of the syndrome (1).

EPIDEMIOLOGY Prevalence

In 2007, 111,000 patients entered the US End-Stage Renal Disease (ESRD) program Prevalence

As of December 31, 2007, a total of 527,283 patients enrolled in the ESRD Medicare-funded program Morbidity

Patients with a diagnosis of uremia may have a 54% perioperative morbidity (ranges from 12% to 64% in 8 published studies) Mortality

Uremic patients undergoing general surgery have a 4% mortality; cardiac surgery 10% ETIOLOGY/RISK FACTORS

The common causes of ESRD include: • Diabetes mellitus (40%)

• Hypertension (27%) • Chronic glomerulonephritis (13%) • Cystic kidney disease (3.5%) • Interstitial nephritis (4%) • Obstructive uropathy • Lupus nephritis • Human immunodeficiency virus

PHYSIOLOGY/PATHOPHYSIOLOGY

• Uremic toxins are comprised of small water-soluble, small lipid-soluble, and larger middle molecules (4). • Small water-soluble compounds (<500 Da) – Urea – Guanidines; some of these arginine-analogs are competitive inhibitors of nitric oxide (NO) synthase (may lead to vasoconstriction and hypertension). Asymmetric dimethylarginine has a strong relationship with cardiovascular events. – Oxalate – Phosphate; increased levels can cause pruritus or hyperparathyroidism – Creatinine is a good marker for renal function; there is no apparent direct adverse effect from its accumulation. • Small lipid-soluble, protein-bound compounds are not effectively removed by current dialysis methods. – Phenols – Homocysteine; renal failure patients typically have levels that are 2–4 times above normal. It is an independent risk factor for cardiovascular disease. – Indoles can induce glomerular sclerosis. – Furanpropionic acid correlates with neurologic abnormalities. • Larger middle molecules (>500 Da) can be filtered by high-flux membranes. – Beta-2-microglobulins are associated with dialysis-related amyloidosis. – Parathyroid hormone – Advanced glycosylation end (AGE) products – Leptin, which suppresses appetite – Proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) – Immune complement components • Indications for renal replacement therapy do not necessarily overlap with uremic toxins – Volume overload – Hyperkalemia – Severe metabolic acidosis – Intoxication of dialyzable substances – Symptomatic uremia

ANESTHETIC GOALS/GUIDING PRINCIPLES

Perioperative management of uremia often overlaps that of renal failure. Uremia specifically describes pathophysiology from the accumulation of organic waste products seen as a result

of renal failure.

PREOPERATIVE ASSESSMENT SYMPTOMS

Symptoms of uremic syndrome History

• Etiology of renal disease • Assess comorbidities

Signs/Physical Exam

• Easy bruising or bleeding • Pleuritic chest pain or pericardial rubs may indicate uremic pericarditis.

TREATMENT HISTORY

Dialysis is the primary treatment. Duration, last treatment, complications, weight change (>2 kg indicates loss of intravascular volume) are important details to inquire about, and allow for coordination postoperatively MEDICATIONS

Phosphate binders, calcitriol, erythropoietin DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, including glucose, calcium, phosphorus, magnesium • BUN and creatinine • PT, PTT • CBC, liver enzymes, albumin, bilirubin • ECG, chest x-ray (CXR) • Stress tests and/or coronary angiography, if indicated. • 2D echocardiography when left ventricular dysfunction or uremic pericarditis is suspected.

CONCOMITANT ORGAN DYSFUNCTION

• Neurologic: Encephalopathy, peripheral neuropathy, memory defects, inability to plan, inattention • Cardiovascular: Accelerated atherosclerosis, hypertension, uremic cardiomyopathy, pericarditis, and volume overload. If revascularization is required, then coronary artery bypass surgery is superior to coronary angioplasty due to the high rate of restenosis in uremic patients. • Gastrointestinal: Gastroparesis, uremic gastroenteritis, nausea, and vomiting • Electrolyte disturbances: Hyponatremia, hyperkalemia, hyperphosphatemia, hypermagnesemia, and hypocalcemia • Metabolic: Insulin resistance may contribute to the accelerated vascular disease seen • Hematologic: Platelet dysfunction correlates with the severity of both uremia and anemia.

Normochromic normocytic anemia may result from marrow suppression by uremic factors (in addition to reduced erythropoietin). • Endocrine: Secondary hyperparathyroidism and glucose intolerance

CIRCUMSTANCES TO DELAY/CONDITIONS

• Dialysis: Non-heparin hemodialysis is preferred on the day of surgery and/or within 24–48 hours after major surgery. – Severe hypertension in uremic patients on dialysis preoperatively may be a signal of volume overload and an indication for dialysis before surgery. – Hyperkalemia and metabolic acidosis should be considered for dialysis before surgery, as well.

TREATMENT PREOPERATIVE PREPARATION Premedications

• Gastric acid reduction: Patients who are uremic and diabetic may have gastroparesis. • Recombinant erythropoietin or darbepoetin may be used in elective surgery to boost hemoglobin level to 12–13 g/dL weeks before the planned procedure. If possible, transfusion should be avoided to decrease leukocyte antigen exposure and increase the successful rate of kidney transplantation if available later on. • Treatment of uremic bleeding includes (1): – DDAVP (desmopressin) 0.3 mcg/kg IV or SC. It lasts for 6–8 hours and increases the circulating level of factor VIII–von Willebrand factor (vWF) complex. – Cryoprecipitate 10 units IV over 30 minutes. The effect lasts for 12–18 hours. It contains factor VIII–vWF complex. – Conjugated estrogen 0.6 mg/kg/day IV for 5 days. The effect lasts for 14 days.

Special Concerns for Informed Consent

Protect the designated arm for future or existing accesses by avoiding needle sticks, BP measurements, or central lines on the same side of the arteriovenous access. INTRAOPERATIVE CARE Choice of Anesthesia

• Neuraxial techniques: Uremic patients usually have normal PT, PTT, and platelet count; however, they may have prolonged bleeding time due to platelet dysfunction. The risks and benefits of epidural placement need to be evaluated carefully. • General anesthesia with ETT is commonly used to decrease the possibility of pulmonary aspiration Monitors

• Standard ASA monitors • Arterial lines should be considered for emergency or major surgery. • Central line pressure monitoring may be appropriate for emergency or major surgery. Use of

ultasound guidance may decrease inadvertent arterial puncture. • Pulmonary artery catheter or transesophageal echocardiography (TEE) should be considered in patients presenting with septic or cardiogenic shock.

Induction/Airway Management

• Airway instrumentation should be gentle to avoid injury and bleeding. • Rapid sequence induction should be considered when gastroparesis is suspected. • Large swings in BP and heart rate are common in uremic and hypertensive patients during intubation. If there is concern about coronary artery disease (CAD), fentanyl 5 μg/kg or esmolol 0.5–1.0 mg/kg can attenuate the response to laryngoscopy.

Maintenance

• Desflurane and isoflurane have been shown to be safe in renally impaired patients. Sevoflurane has theoretical potential for renal toxicity from its metabolite fluoride or its byproduct compound if used with sodium or barium hydroxide lime absorbents. • Avoid nondepolarizing muscle relaxants that require renal clearance, including pancuronium, rocuronium, and vecuronium. Cisatracurium and atracurium are eliminated via Hoffman degradation and are preferred in uremic patients. Dosing of reversal agents does not change; 50% of neostigmine is cleared by the kidneys. The prolonged clearance of anticholinesterase drugs gives some protection against residual blockade. • The opioids fentanyl, sufentanil, alfentanil, and remifentanil are cleared primarily by the liver, and thus preferred. Morphine’s acive metabolite, morphine-6-glucuronide (M6G), accumulates in renal failure and has CNS and respiratory depressive effects. Meperidine is metabolized to normeperidine that can accumulate in renal failure and cause seizures. • Traditionally, the intraoperative fluid of choice is normal saline. However, large amounts of normal saline can cause hyperchloremic metabolic acidosis, which can increase hyperkalemia, compared to lactated Ringer’s solution (2). • Transfusion of multiple units of packed red blood cells in uremic patients can worsen hyperkalemia. If transfusion is anticipated, intraoperative continuous venovenous hemodialysis (CVVHD) should be arranged. Continuous venovenous hemofiltration (CVVH) removes fluid but not solute. It is used solely for volume overload (3).

Extubation/Emergence

Medication clearance may be prolonged. Ensure that neuromuscular blocking drugs are reversed and that the patient is fully awake.

FOLLOW-UP BED ACUITY

• PACU, then floor or telemetry • ICU if unstable

MEDICATIONS/LAB STUDIES/CONSULTS Dialysis

COMPLICATIONS Uremic bleeding

REFERENCES

1. ines RL, Marschall KE, et al. Anesthesia and co-existing disease. Churchill Livingstone. 2008:332–333. 2. O’Malley CM, et al. A randomized, double-blind comparison of lactated Ringer’s solution and 0.9% NaCl during renal transplantation. Anesth Analg. 2005;100:1518–1524. 3. Petroni KC, Cohen NH. Continuous renal replacement therapy: Anesthetic implications. Anesth Analg. 2002;94:1288–1297.

4. Vanholder R, et al. Review on uremic toxins: Classification, concentration, and interindividual variability. Kidney Int. 2003;63:1934–1943.

ADDITIONAL READING

• Kasper DL, et al.Harrison’s Principles of Internal Medicine, 16th ed. New York, NY: McGrawHill, 2005:267, 1654–1657.

See Also (Topic, Algorithm, Electronic Media Element) • Hyperkalemia • Acute renal failure • End-stage renal disease

CODES ICD9 • 585.9 Chronic kidney disease, unspecified • 586 Renal failure, unspecified ICD10 • N18.9 Chronic kidney disease, unspecified • N19 Unspecified kidney failure

CLINICAL PEARLS

• Perioperative care of the uremic patient has special considerations, in addition to those of renal failure. Uremia is a subset illness of renal disease; it is not mutually exclusive and cannot be viewed in “isolation.” • Treatment of uremic bleeding includes DDAVP, cryoprecipitate or conjugated estrogen.

URETERAL REIMPLANTATION Rebecca A. Drinkaus, MD

BASICS DESCRIPTION General

• Ureteral reimplantation is an open or laparoscopic procedure where the ureters are reimplanted in the bladder wall. The procedure treats a condition known as vesicoureteral reflux (VUR), where abnormally positioned ureters allow retrograde flow of urine into the renal collecting system. • Uncorrected VUR can lead to recurrent UTI, dilation of the ureter, pyelonephritis, and renal scarring. When disease is severe, it can lead to hypertension, growth impairment, and renal insufficiency (1). • Types of VUR – Primary (presents in childhood): Most common form of reflux and is due to incomplete closure of the ureterovesical junction (UVJ) which is caused by a relatively short intravesical ureter. – Secondary: Associated with an abnormally high pressure in the bladder that results in failure of the UVJ to close during bladder contraction. • The decision to treat medically with antibiotics or surgically is made on the basis of the grade of VUR, age, and symptoms. • The International Reflux Study Group (IRSG) grades VUR on the basis of the degree of retrograde filling and dilation of the urinary system. – Grade I (mild): Reflux only fills the ureter without dilation. – Grade II (mild): Reflux fills the ureter and the collecting system without dilation. – Grade III (moderate): Reflux fills and mildly dilates the ureter and collecting system with mild blunting of the calyces. – Grade IV (severe): Reflux fills and grossly dilates the ureter and the collecting system with blunting of the calyces. Some tortuosity of the ureter is also present. – Grade V (severe): Massive reflux grossly dilates the collecting system. All the calyces are blunted with a loss of papillary impression, and intrarenal reflux may be present. There is significant ureteral dilation and tortuosity. • Initial treatments for VUR include continuous antibiotic prophylaxis (CAP) and endoscopic injection of dextranomer/hyaluronic acid copolymer. • VUR is usually observed in children; however, it may present itself after puberty and in adulthood. In many cases, lower-grade VUR resolves spontaneously. Spontaneous resolution without treatment can occur within 24 months of diagnosis in 61% of patients. • There are various methods of surgical repair including intravesical and extravesical reimplantation techniques. • Laparoscopic ureteral reimplantation is associated with shorter hospital stays and reduced

blood loss, but it is technically challenging.

Position Supine

Incision

Low transverse

Approximate Time 2–4 hours

EBL Expected

Often <100 mL for pediatric open procedure Hospital Stay

Average of 3 days for open procedure (2)

Special Equipment for Surgery

• Cystoscopy equipment; often performed prior to reimplantation to confirm anatomy and the presence of inflammation or infection • Laparoscopic equipment

EPIDEMIOLOGY Prevalence

• Diagnosed in 1% of the pediatric population • Based upon ethnicity, gender, and age of patient. VUR is more common in females; however, during infancy, males present more frequently with more severe VUR. The incidence of VUR is also less in African-American children (3).

Prevalence

• Has not been established due to variations in severity, lack of symptoms, and lack of noninvasive diagnostic tools. • There is a strong genetic predisposition for primary VUR with a prevalence of 27.4% in siblings and 35.7% for children of an affected parent (4).

Morbidity

The success rate for this surgery is about 98%. Mortality

Surgical risk in patients without comorbidities is low. ANESTHETIC GOALS/GUIDING PRINCIPLES

• Regional anesthesia can be used for intraoperative and postoperative pain control. • Reduction of bladder spasms in the postoperative period • Maintain hydration and adequate urine output

PREOPERATIVE ASSESSMENT SYMPTOMS

• UTI (fever, dysuria, urinary frequency, poor feeding) • Symptoms of bowel and bladder dysfunction (BBD): Urinary frequency and urgency, prolonged voiding intervals, daytime wetting, perineal/penile pain, holding maneuvers, constipation/encopresis • Patients may be asymptomatic even when renal scarring is present.

History

• History of repeated UTI even while on antibiotic treatment • Assess for contraindications to regional anesthesia • Any history of renal insufficiency

Signs/Physical Exam

• Routine examination will show few signs unless severe renal disease exists. • Assess for hypertension

MEDICATIONS

Antibiotics for infection

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Serum creatinine • Serum electrolytes • Urine culture should be ordered several weeks prior to surgery in order to treat any existing infection. • Voiding cystourethrogram (VCUG), radionuclide cystography (RNC) • Renal imaging with dimercaptosuccinic acid (DMSA) can show renal cortical damage and scarring.

CONCOMITANT ORGAN DYSFUNCTION Assess for history of renal insufficiency.

TREATMENT PREOPERATIVE PREPARATION Premedications

Benzodiazepines as appropriate for preoperative anxiety. Oral administration should be performed 30 minutes prior to the procedure if no IV exists for maximum absorption and effect. Special Concerns for Informed Consent

• Potential to convert from laparoscopic to open procedure • Consent for regional procedures

Antibiotics/Common Organisms

• Patients are placed on CAP but may develop infection in spite of treatment. Trimethoprim– sulfamethoxazole, trimethoprim, and nitrofurantoin may be given for antibiotic prophylaxis. • The most common organism for pediatric UTI is Escherichia coli followed by other gramnegative organisms.

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with endotracheal tube (ETT). • Regional anesthesia techniques (caudal +/− catheter or epidural catheter) can be used as a supplement to general anesthesia. If the suspicion of bladder inflammation or infection is high, regional blocks are often placed after a cystoscopy is performed (in the event that the case is cancelled).

Monitors

• Standard ASA monitors • 1–2 peripheral IV catheters are typically adequate. • Foley catheters are usually placed on the field by the surgeon; however, because placement has been associated with longer hospital stay and bladder spasms in some studies, some surgeons may not place a catheter. If a regional block is considered beneficial, discuss with the surgical team their plan for Foley placement. Consider doing a single shot caudal at the beginning and end of the surgical case or removal of caudal or epidural catheters after dosing at the end of the case if no urinary catheter is placed.

Induction/Airway Management

Mask induction with nitrous oxide and sevoflurane may be done prior to IV placement. Nitrous may also be used for placement of an IV and followed by IV induction in anxious older children or teenagers. Maintenance

• Air–oxygen mixtures are well tolerated. Nitrous should be avoided in laparoscopic procedures to avoid gastric distension. • Muscle relaxation may be used throughout the entire procedure and is necessary for laparoscopic procedures. • Analgesia: Low-dose narcotics are used with both open and laparoscopic cases; dosing can be titrated to respiratory rate at the end of the case, as narcotics can contribute to urinary retention. Epidural anesthesia can be considered for continuous analgesia intraoperatively as a narcotic sparing technique. • Age, weight, and comorbidities should be considered when dosing any medication. • Laparoscopic cases should be monitored for complications including pneumoperitoneum and air embolism. • Fluids: Urine measurement is not always readily available and fluid losses are not large.

Maintenance fluids and insensible losses should be replaced. • Consider rotation of the BP cuff to another extremity if a long surgical time is expected.

Extubation/Emergence

• Redose regional anesthetic or narcotic prior to extubation. • Consider administering the first dose of ketorolac prior to emergence. In patients with impaired renal function, may consider avoiding.

FOLLOW-UP BED ACUITY

Floor bed with oximetry ANALGESIA

• IV narcotics (fentanyl, morphine, hydromorphone) can be used postoperatively for incisional pain. Respiratory depression may occur if IV narcotics are given concurrently with intrathecal narcotics. • Continuous epidural anesthesia can be used for postoperative pain. PCEA should be considered only in those patients physically and cognitively able to push a button. In general, these patients are over 7 years of age. It is best used in teenage patients or older who can tolerate larger doses of anesthetic with few side effects. • Bladder spasm pain is common postoperatively. Ketorolac has been shown to decrease the frequency and severity of bladder spasm and to be associated with reduced hospital length of stay.

COMPLICATIONS

• Persistent VUR with UTI • Contralateral reflux can occur with unilateral repair • Obstruction from edema, blood clots, or submucosal hematoma. A follow-up renal ultrasound is recommended after the procedure to assess for obstruction.

PROGNOSIS

• Resolution of reflux following open surgery: 98% • Resolution rate following endoscopic injection: 50%–92%

REFERENCES

1. Peters CA. Summary of the AUA guideline on management of primary vesicoureteral reflux in children. J Urology. 2010;184:1134–1144. 2. Routh JC. Ketorolac is underutilized after ureteral reimplantation despite reduced hospital cost and reduced length of stay. Urology. 2010;76(1):9–13. 3. Chand DH. Incidence and severity of vesicoureteral reflux in children related to age, gender, race and diagnosis. J Urology. 2003;170(4):1548–1550. 4. Skoog SJ. Pediatric vesicoureteral reflux guidelines panel summary report: Clinical practice

guidelines for screening siblings of children with vesicoureteral reflux and neonates/infants with prenatal hydronephrosis. J Urology. 2010;184:1145–1151.

ADDITIONAL READING •

American Urology Association clinical guidelines http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines.cfm • NYSORA Pediatric Epidural Analgesia and Anesthesia in Children http://www.nysora.com/ • Smellie JM. Medical versus surgical treatment in children with severe bilateral vesicoureteric reflux and bilateral nephropathy: A randomized trial. Lancet. 2001;357:1329–1333. See Also (Topic, Algorithm, Electronic Media Element)

• Epidural • Caudal • Laparoscopy

CODES ICD9 593.70 Vesicoureteral reflux unspecified or without reflux nephropathy ICD10 N13.70 Vesicoureteral-reflux, unspecified

CLINICAL PEARLS

• Regional anesthesia techniques can provide good pain control. • Administration of ketorolac for bladder spasm may improve patient satisfaction and decrease hospital stay. • Antibiotics are continued during the intraoperative and postoperative periods. • The prognosis is excellent for all ureteral reimplantation techniques.

URINE OSMOLALITY

Andaleeb Abrar Ahmed, MBBS, MD, MPH Jill Eckert, DO

BASICS DESCRIPTION

• Urine osmolality is a measure of the concentration of osmotically active particles; it can range from 50 (maximally dilute urine) to 1,200 (maximally concentrated urine) mOsm/kg. Primary particles include: – Sodium – Chloride – Potassium – Urea • This measured value is used to assess: – Plasma electrolyte and fluid balance – Concentrating and diluting ability of the kidney in response to plasma osmolality • In normal physiologic conditions, urine specific gravity corresponds to urine osmolality.

PHYSIOLOGY PRINCIPLES

• Terminology. – One osmole: The amount of particles equal to Avogadro’s number (6.02 × 1023). – Osmolarity: The amount of osmotically active particles present per liter of solution (mmol/L). – Osmolality: The amount of osmotically active particles present per kilogram of solvent (mmol/kg). For dilute solutions, osmolarity and osmolality can be used interchangeably. – Tonicity: The osmotic pressure of two solutions separated by a semipermeable membrane. Solutes that can cross will reach equilibrium. Thus tonicity results from solutes that cannot cross the membrane. In the body, tonicity refers to the state of the extracellular fluid (ECF compared to that of the intracellular fluid). • The kidney regulates urine concentration (and osmolality) by 3 physiologic processes: – Maintenance of a hypertonic medullary interstitium by countercurrent exchangers and urea cycling. This is an active transport and energy consuming process. – Different water permeabilities of the ascending and descending loops of Henle. – Effect of arginine vasopressin (AVP; formerly ADH) on distal tubules and collecting ducts. It increases water permeability via effects on V2 receptors. Water flows down an osmotic

gradient into the hyperosmotic renal medulla. AVP is normally released in response to increased serum osmolarity; nonosmotic stimuli include pain, nausea, emotional stress, and decreased ECF volume. • Serum osmolality: The osmotic threshold ranges from 270 to 290 mOsm/kg. Sodium is the primary plasma electrolyte and determines plasma osmolality; thus, changes in sodium ion concentration reflect/accompany disturbances in water balance.

– Plasma hypoosmolality: Decreased AVP release causing the excretion of a dilute urine Low urine osmolality (<100 mOsm/kg) Low specific gravity (<1.003) Kidneys retain sodium – Plasma hyperosmolality: Increased AVP release causing the excretion of a concentrated urine High urine osmolality (>200–300 mOs/kg) High specific gravity (>1.02)

ANATOMY

• Osmoreceptors are located in the paired supraoptic and paraventricular nuclei of the anterior hypothalamus, where AVP is also synthesized. When stimulated (e.g., hyperosmolality, decreased ECF volume), AVP is axonally transported to the posterior pituitary for secretion. • G-protein–coupled V2 receptors, located on the basolateral cell membrane of the collecting duct, respond to AVP. AVP-induced activation of V2 receptors causes insertion of aquaporin-

2 water channels in the apical membrane of principal cells in the collecting duct (1).

PHYSIOLOGY/PATHOPHYSIOLOGY

• Urine osmolality is utilized in correlation with clinical history and examination, plasma osmolality, serum sodium, and volume status to differentiate between causes of hypernatremia and hyponatremia, as well as polyuria, SIADH, and cerebral salt wasting (CSW). • Urine osmolality is elevated (concentrated urine) in the following conditions: – Dehydration/hypovolemia – SIADH – Postoperative state – Solute diuresis (glycosuria, mannitol, radiocontrast agents) – High protein feeding – Resolving acute tubular necrosis – Postobstructive diuresis – Mineralocorticoid and glucocorticoid deficiencies – Congestive heart failure, cirrhosis – Hypothyroidism from nonosmotic release of AVP (3). – Drugs: Carbamazepine, SSRI, oxytocin, cyclophosphamide, clofibrate, vincristine, chlorpropamide, DDAVP • Urine osmolality is decreased (dilute urine) in the following conditions: – Diabetes insipidus – Polydipsic states (psychiatric) – Hypotonic IV fluids – Acute tubular necrosis – Drug: Lithium, demeclocycline, glyburide, tolazamide • Dehydration/hypovolemia may present with hypotension, tachycardia, and decreased skin turgor. Lab findings:

– Urine osmolality: Increased – Urine volume: Decreased – Serum osmolality: Typically increased – Serum sodium: Both hypernatremia and hyponatremia can occur – Total body sodium: Decreased • Postoperative state (high AVP state) – Urine osmolality: Increased – Urine volume: Variable – Serum osmolality: Decreased – Serum sodium: Decreased – Total body sodium: Unchanged or decreased • Solute diuresis – Urine osmolality: Increased – Urine volume: Increased – Serum osmolality: Typically increased – Serum sodium: Depends on the type of solute – Total body sodium: Decreased • Mineralocorticoid and glucocorticoid deficiency – Urine osmolality: Elevated – Urine volume: Decreased or normal – Serum osmolality: Variable – Serum sodium: Decreased – Total body sodium: Typically decreased with mineralocorticoid deficiency, and normal with glucocorticoid deficiency • Congestive heart failure and cirrhosis – Urine osmolality: Decreased – Urine volume: Variable – Serum osmolality: Decreased – Serum sodium: Decreased – Total body sodium: Increased • SIADH and CSW may present after a neurosurgical procedure or CNS insult with hypoosmolar hyponatremia. Lab findings: – Urine osmolality: Increased – Urine volume: Decreased – Serum osmolarity: Decreased – Serum sodium: Decreased – Total body sodium: Normal • Central diabetes insipidus can develop after a hypophysectomy, injury to the pituitary stalk, head trauma, supra- or interstellar tumor/cyst. Lab findings: – Urine osmolality: Decreased (<250 mOsm/L) – Urine volume: Increased – Serum osmolarity: Increased – Serum sodium: Increased – Total body sodium: Normal

PERIOPERATIVE RELEVANCE

• General anesthesia may interfere with urinary concentrating capacity despite an increase in plasma AVP. • In the postoperative period, nonosmotic release of AVP, along with hypotonic IV fluid administration can lead to hyponatremia (with elevated urine osmolality). • Inert fluids containing glycine, sorbitol, or mannitol are used for irrigation during transurethral resection of the prostate (TURP). They can be rapidly absorbed via open venous sinuses in the prostate gland causing hyponatremia, volume overload, and hypoosmolality. • Methoxyflurane has been associated with polyuric nephrotoxicity especially at doses >1 MAC for 2 hours (2 MAC hours). This volatile agent is no longer used in developed countries.

EQUATIONS

• Free water clearance (CH2O) = V - {Uosm/Posm} × V, where Uosm (mOsm/kg) = Urine osmolality, Posm (mOsm/kg) = Plasma osmolality, and V = urine flow rate. CH2O is a

measure of water regulation by renal tubules. CH2O >0 implies that the kidney is producing dilute urine, whereas CH2O <0 means that the kidney is conserving water, likely under the

influence of AVP • Urine-to-plasma osmolality ratio (Uosm:Posm) of >1.5 indicates an intact urine concentrating ability, whereas isosthenuria (Uosm:Posm = 1) in the setting of acute renal failure indicates

ATN (in the absence of diuretics). • Calculated plasma osmolality (mOsm/kg) = (2 × [Na+]) + (BUN/2.8) + (glucose/18) (1). • Estimated total body water (TBW) = Weight (kg) × fraction of body weight (%). Fraction is 0.6 in children; 0.6 and 0.5 in nonelderly men and women, respectively; and 0.5 and 0.45 in elderly men and women, respectively (2). • Sodium deficit (mEq/L) = TBW × ([Na+]desired + [Na+]current)

REFERENCES

1. in M, Liu SJ, Lim IT. Disorders of water imbalance. Emerg Med Clin North Am. 2005;23(3):749–770. 2. Adrogué HJ. Hyponatremia. N Engl J Med. 2000;342(21):1581–1589. 3. Adler SM, Verbalis JG. Disorders of body water homeostasis in critical illness. Endocrinol Metab Clin North Am. 2006;35(4):873–894. 4. Esson ML, Schrier RW. Diagnosis and treatment of acute tubular necrosis. Ann Intern Med. 2002;137(9):744–752. 5. Decaux G, Musch W. Clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol. 2008;3(4):1175–1184. See Also (Topic, Algorithm, Electronic Media Element) • Extracellular fluid

• Hyponatremia • Hypernatremia

CLINICAL PEARLS

• Urine osmolality, in addition to history, symptoms, signs, physical examination, serum sodium and osmolality, and urine volume, can aid in the diagnostic workup of hyponatremia, hypernatremia, polyuria, CSW, and diabetes insipidus.

URINE OUTPUT

Jiadong Wei, MD Jean Charchaflieh, MD, DrPH, FCCM, FCCP

BASICS DESCRIPTION

• Urine output (UO) is the volume of urine produced over a certain period of time. It varies depending upon volume status, renal function, renal perfusion, and physiologic demands. • Normal UO is >0.5–1 mL/kg/hr for adults (e.g., 30–40 mL/hr for an average-sized adult) and close to 1 mL/kg/hr for children. • UO is dependent on: – Hydraulic and oncotic pressures within the glomerular capillary – Local and systemic neurohumoral influences – An intact kidney–ureter–bladder feedback loop • Changes in UO serve as an early indicator of systemic complications, such as inadequate organ perfusion/shock, acute renal dysfunction, dehydration or hemorrhage, and fluid overload PHYSIOLOGY PRINCIPLES

• Renal blood flow (RBF) constitutes about 20–25% of the cardiac output (CO); the kidneys constitute about 0.5% of total body weight. • The pressure within the renal arterioles in the glomerulus drives the ultrafiltration of fluids and solutes into the Bowman’s capsule. As the ultrafiltrate courses through the renal tubules, its volume is reduced by reabsorption of water and solutes, and secretion of waste products takes place. • Glomerular filtration rate (GFR), is the rate at which blood is filtered through glomeruli and normally has a value of 90–120 mL/min. GFR can be measured by IV administration of a non-toxic, non-metabolized, and freely filtered substance that is neither reabsorbed nor secreted in the tubules (e.g., inulin or creatinine). Increased GFR may result from dilation of the afferent arteriole, constriction of the efferent arteriole, or increase in the BP. • Hormones – Angiotensin II has several effects on the nephron. It increases mean arterial BP; constricts efferent > afferent arterioles; increases active transport of Na+ out of the proximal convoluted tubule (PCT) into plasma and elicits the release of prostaglandins. Consequently, its effect on RBF and UO is variable. – Prostaglandins dilate blood vessels in the renal cortex and constrict those in the renal medulla (increased RBF and UO) – Both the parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) increase the active transport of phosphate (PO43−) back into the blood (increased UO) – Aldosterone increases the reabsorption of Na+ in the distal convoluted tubule (DCT) and

the collecting tubules (decreased UO) – The release of vasopressin (antidiuretic hormone [ADH]) release from the posterior lobe of the pituitary gland is regulated by the serum osmolarity. Release of ADH results in water reabsorption from the DCT and collecting tube (decreased UO) • Ureteral peristalsis (UP) and interaction between the bladder, the kidneys, and the ureters (kidney–ureter–bladder feedback loop) also influence RBF and UO. • Urine is stored in the bladder before micturition, which is under both voluntary control and spinal reflex pathways.

ANATOMY

• Each kidney contains ∼1 million nephrons, which are composed of a glomerulus and renal tubules (Figure 1). • A glomerulus is a capillary tuft that is surrounded by the Bowman’s capsule, which connects to the renal tubules. • Arterial blood reaches the glomerulus via an afferent arteriole and leaves via a smaller efferent arteriole.

PHYSIOLOGY/PATHOPHYSIOLOGY

• Abnormal UO: – Oliguria: Adults and children <0.5 mL/kg/hr; infants <1 mL/kg/hr – Anuria: <50 mL/hr. Acute anuria is usually a sign of obstruction or acute renal failure (ARF); whereas chronic anuria usually occurs with end-stage renal disease (ESRD). – Polyuria: Adults >3 Liters/24 hours; children >2 L/m2/24 hrs. It results from physiologic, pharmaceutical, or pathologic causes such as excretion of non-absorbable solutes or water. Frequency or nocturia is not necessarily associated with polyuria. • Acute kidney injury (AKI): Associated with oliguria (worse prognosis), polyuria, or normal UO, and has a very high mortality rate. Urinary diagnostic indices help differentiate prerenal from intra-renal AKI (Table 1). – Pre-renal AKI can result from decreased perfusion or hypovolemia (e.g., poor oral intake, hemorrhage; cardiogenic, anaphylactic, septic shock) – Intra-renal AKI can result from acute tubular necrosis (including rhabdomyolysis and toxic nephropathy), glomerulonephritis, vascular disease, and interstitial nephritis. The oliguric phase of ATN can last 1–6 weeks and can be followed by a diuretic phase. UO is used for diagnosing and staging. – Post-renal AKI can result from obstruction of urine flow (e.g., inability to void, benign prostatic hypertrophy, prostate cancer, cervical cancer, retroperitoneal fibrosis, retroperitoneal lymphoma, metastatic carcinoma, and nephrolithiasis). • 2 commonly used systems to stage AKI; both systems utilize either the UO or serum creatinine (SCr), whichever is worse. – RIFLE: Risk, Injury, Failure, Loss, End-stage kidney disease. The first 3 stages (Risk, Injury, Failure) reflect the severity of AKI and correspond to the 3 stages of AKIN. The last 2 stages (loss, end-stage kidney disease) reflect the duration of AKI. – AKIN: Acute Kidney Injury Network. – Stage R (AKIN stage 1) is defined as a 0.3 mg/dL increase from baseline in (SCr) or UO <0.5 mL/kg/hr for 6 hours. Stage I (AKIN stage 2) is defined as an increase in SCr to

twice the baseline or UO <0.5 mL/kg/hr for 12 hours. Stage F (AKIN stage 3) is defined as an increase in SCr to 3 times the baseline or UO <0.3 mL/kg/hr for 24 hours or anuria for 12 hours. • Chronic kidney disease (CKD): In early CKD, the kidney loses its concentrating function resulting in the excretion of dilute urine (polyuria, nocturia). In advanced CKD, the kidney loses both concentrating and diluting functions; therefore, the osmolality of the urine becomes similar to that of plasma. Loss of kidney function is mostly due to loss of functioning nephrons and partly due to disruption of the countercurrent mechanism located in the medulla. Injury will eventually progress to the functioning nephrons due to increased, compensatory filtration that ultimately overwhelms and damages them. • Diabetes insipidus – Central diabetes insipidus (CDI) is caused by decreased release of ADH from the hypothalamic osmoreceptors: The supraoptic (paraventricular) nuclei or the superior portion of the supraoptico-hypophyseal tract. The vast majority of cases of CDI result from neurosurgery, trauma, tumors, infiltrative diseases, or idiopathic mechanisms. Additional causes include hypoxic encephalopathy, Wolfram syndrome, post-supraventricular tachycardia (SVT), and anorexia nervosa. – Nephrogenic diabetes insipidus (NDI) results from renal tubular resistance to ADH. NDI can be hereditary (vasopressin V2 or aquaporin-2 gene mutation) or drug related (lithium, cidofovir, or hypercalcemia). – Plasma ADH level is the best method for distinguishing between CDI and NDI. – Water deprivation test plus exogenous ADH is used to distinguish primary polydipsia from both CDI and NDI.

PERIOPERATIVE RELEVANCE

• General anesthesia (GA), stress, trauma, and surgery (particularly aortic cross-clamping and declamping) influence renal function primarily by affecting filtration and reabsorption. Mechanisms include sympathetic activity, renin–angiotensin–aldosterone system (RAAS), intravascular volume, systemic vascular resistance (SVR), CO, BP, RBF, and nephrotoxins. • Volatile versus IV anesthesia: Both techniques can decrease BP, CO, and SVR; redistribute RBF; and increase Na+ and H2O reabsorption leading to decreased UO.

• Drugs – Norepinephrine in small doses (0.2 mcg/kg/min) may preferentially constrict efferent arterioles (increased RBF and UO). Large doses (2 mcg/kg/min) constrict all blood vessels (decreased RBF and UO). – Dopamine in small doses (2 mcg/kg/min) may preferentially dilate renal blood vessels (increased RBF and UO). – Narcotics and barbiturates can produce a small decrease in GFR, which might lead to postoperative oliguria. • Ureteral peristalsis (UP) – Increased UP may increase UOP: Cholinergic agonists, adrenergic receptor antagonists, histamine, and possibly morphine. – Decreased UP may decrease UO: Adrenergic receptor agonists. • Regional anesthesia (RA) above T4 leads to a sympathectomy-induced loss of autoregulation

of RBF; thus, RBF and filtration are directly dependent on perfusion pressure. Additional factors influencing UO during RA include circulating catecholamines, RAAS, ADH, steroids, and prostaglandins. • Postoperative AKI: Oliguric AKI, particularly in older patients, is associated with increased mortality and long-term renal injury compared to non-oliguric AKI. • Systemic diseases may impair urine transport (e.g., UTI, appendicitis, regional enteritis, ulcerative colitis, and peritonitis). • Postoperative AKI risk factors: – Age >65 years – Emergency surgery – High-risk surgery – Cardiac disease: Ischemic heart disease, congestive heart disease, cardiac risk index (RCRI) score >2. – ASA physical status IV/V • Intraoperative oliguria: Patients with a Foley catheter should have their UO monitored at least every 30 minutes. Decreases should prompt an assessment of potential possibilities: – Pre-renal: Hypovolemia (secondary to fluid deficits, hemorrhage, or insensible losses) or decreased renal perfusion pressures from hypotension or certain medications. Pre-renal factors are the most common cause of oliguria in the perioperative period; however, postrenal and intra-renal causes should also be considered. – Post-renal: Improperly placed or kinked Foley catheter; distal drain tip opposite of fluid urine level (e.g., tip lies toward the anterior dome of the bladder while the urine is gravity dependent and lies toward the posterior dome). – Intra-renal: ATN from nephrotoxic drugs, rhabdomyolysis, or prolonged pre-renal causes. – Consider a fluid challenge: Typically performed as a bolus of 10% of the intravascular volume (e.g., a 75 kg male has an intravascular blood volume of ∼4900 mL; 10% is 490 mL and thus a crystalloid bolus that is 3 times that will result in a 10% increase). Reassess for diuresis. If unsuccessful, consider repeating a 5–10% fluid challenge. For patients with congestive heart failure or renal disease, consider a smaller first and second bolus.

EQUATIONS

Normal GFR (90–120 mL/min) varies according to age, sex and body size. • Schwartz pediatric GFR: GFR = (Δ × height [cm])/Scr (Δ is 0.33 for low birth weight infants, 0.45 for term infants, 0.55 for children 2–12 yrs and girls 13–21 yrs, and 0.70 for boys 13–21 yrs) (1). • Adult estimated GFR (eGFR), also called creatinine clearance (Ccr). Cockcroft-Gault equation: Ccr = (140-age) × weight × 0.85 (if female) × 1.73)/(72 Scr × BSA) (2). • Modification of Diet in Renal Disease (MDRD) equation: GFR = 175 × standardized Scr 1.154 × age - 0.203 × 1.212 (if black) × 0.742 (if female) (3). • Fractional excretion of Na (FENa) = Urine Na/Plasma Na ÷ Urine creatinine/Plasma creatinine (4). • Renal failure index (RFI) = Urine Na × Plasma Creatinine/Urine Creatinine (5).

GRAPHS/FIGURES

FIGURE 1. EKG waves, segments, and intervals

Table 1 Urinary diagnostic indices

REFERENCE

1. chwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am. 1987;34:571–590. 2. evey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145(4):247–254. 3. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. 4. Abelha FJ, Botelho M, Fernandes V, et al. Determinants of postoperative acute kidney injury. Crit Care. 2009;13(3):R79. 5. Macedo E, Malhotra R, Claure-Del Granado R, et al. Defining urine output criterion for acute kidney injury in critically ill patients. Nephrol Dial Transplant. 2011;26(2):509–515. See Also (Topic, Algorithm, Electronic Media Element) • Glomerular filtration rate (GFR) • Renal blood flow • Uremia • Creatinine clearance

CODES

ICD9

• 788.42 Polyuria • 788.5 Oliguria and anuria ICD10

• R34 Anuria and oliguria • R35.8 Other polyuria

CLINICAL PEARLS

• Any patient under fluid resuscitation and/or close fluid management requires precise UO information. Fluid monitoring is crucial for critically ill patients. • Real-time and accurate monitoring of UO can improve the clinical management of patients in the ICU and allow early recognition of AKI. • UO appears to be a valid criterion with prognostic value in patients with AKI. • Diuretics are therapeutically used to increase UOP and/or alter electrolyte levels (can also be an unwanted side-effect). Carbonic anhydrase inhibitors act on the proximal convoluted tubule; loop diuretics in the ascending loop of Henle; thiazide diurectics in the distal tubule; potassium-sparing diuretics in the aldosterone-sensitive principle cells of the cortical collecting tubule.

UTERINE BLOOD FLOW Andrea Parsons, MD

BASICS DESCRIPTION

• The exchange of oxygen, carbon dioxide, metabolites, and drugs between the maternal and fetal circulation takes place within the placenta. Maternal and fetal blood exchange occur as blood flows around the chorionic villi. • Uterine blood flow (UBF) supplies the placenta and myometrium and dramatically increases during pregnancy to meet the demands of the placenta and fetus. • At term, uteroplacental blood flow is around 600 mL/minute due to maximal dilation of uterine arteries. Thus, flow is mainly dependent on maternal blood pressure (1).

PHYSIOLOGY PRINCIPLES

• UBF is proportional to the uterine perfusion pressure (defined as the uterine arterial pressure [UAP] minus the uterine venous pressure [UVP]) divided by the uterine vascular resistance (UVR). • At pregnancy, a complex relationship develops between the uterus and placenta with maternal spiral arteries from the uterus invading the placenta. A low vascular resistance system is established.

ANATOMY

• Uterus and placenta: Blood flows to the uterus via the left and right uterine arteries and then through the endometrial arteries. 90% of blood flows into the intervillous space in the placenta. Next, blood flows through to the chorionic villi, where maternal and fetal blood exchange occurs. • Placenta to the fetus: Oxygenated and nutrient-rich blood flows from the placenta to the fetus via 1 umbilical vein. • Fetus to mother: Deoxygenated blood from the fetus returns to the placenta via 2 umbilical arteries. From the placenta, blood flows into maternal endometrial veins to the uterine veins.

DISEASE/PATHOPHYSIOLOGY

• In the peripartum period, impairment of UBF can be discussed or conceptualized within the context of: – Decreased uterine arterial pressure (UAP) – Increased uterine venous pressure (UVP) – Increased uterine vascular resistance (UVR) • Decreased uterine artery pressure can result due to systemic hypotension: – Supine hypotension syndrome results from aortocaval compression. The gravid uterus compresses the inferior vena cava leading to decreased venous return, decreased cardiac

output, and systemic hypotension. Compression of the abdominal aorta directly decreases uterine perfusion pressure. – Neuraxial anesthesia (spinal and epidural anesthesia): Sympathectomy leads to venodilation, decreased cardiac output, and systemic hypotension – General anesthesia: Induction medications lead to decreased systemic vascular resistance and hypotension. • Increased uterine venous pressure decreases the pressure gradient that favors flow through the uterus: – Vena caval compression – Valsalva maneuvers – Uterine contractions – Drug-induced uterine hypertonia (oxytocin or cocaine use) • Increased uterine venous resistance: – Vasopressor administration (particularly alpha-1 agonism). However, the vasoconstrictor effects are countered by local endothelial effects within the uterine artery – Dysfunctional endothelium (e.g., preeclampsia) – Pregnancy induced hypertension • Uteroplacental insufficiency describes inadequate blood flow to the placenta during pregnancy and/or labor. It can result in intrauterine growth restriction during pregnancy and can lead to signs of fetal distress (e.g., fetal decelerations) during labor. – Fetal abnormalities: Placental developmental abnormalities, uteroplacental vasculature abnormalities, and acquired obstruction (e.g., umbilical cord prolapse). – Maternal diseases: Chronic hypertension, gestational hypertension, preeclampsia, autoimmune disorders, renal or vascular disorders. In addition, chronic hypoxemia and substance abuse can also lead to uteroplacental insufficiency. • Placental abruption, defined as decidual hemorrhage leading to premature separation of the placenta prior to the fetal delivery, can cause uteroplacental insufficiency. Causes include: – Acute trauma – Hypertension – Preterm premature rupture of membranes – Uterine tachysystole (hypertonic contractions) – Ischemic placental disease – Thrombophilias – Uterine wall abnormalities (e.g., fibroids) – Cocaine, tobacco use

PERIOPERATIVE RELEVANCE

• Fetal heart rate (FHR) monitoring is a non-invasive tool to aid in the assessment of fetal wellbeing. Uteroplacental insufficiency is often evidenced by non-reassuring FHR patterns. FHR monitoring is classified as reassuring, non-reassuring, and ominous (2). • Reassuring patterns include: – Baseline FHR 110–160 bpm – Good variability 6–25 bpm – Age-appropriate FHR accelerations – Absence of late or variable decelerations

• Non-reassuring patterns include: – Absent, minimal, or marked variability – Recurrent late decelerations, which reflect a CNS reflex to hypoxia – Recurrent variable decelerations, which generally occur with umbilical cord compression – Prolonged bradycardia – Sinusoidal heart rate pattern • Fetal scalp stimulation or fetal pH determination (less frequently done) can be performed to assess the significance of the pattern. Failure to respond to fetal acidemia (pH <7.20) has been correlated with low Apgar scores and poor outcome (hypoxic ischemic encephalopathy, intraventricular hemorrhage, and cerebral palsy). • Persistent non-reassuring FHR or ominous heart rate patterns (sustained bradycardia) lead the obstetricians to perform a Cesarean section. • Oxygen administration with a face mask, partial rebreather mask, or non-rebreather mask. • Left uterine displacement: A maneuver to help avoid supine hypotension syndrome and aortocaval compression. Displacement can be simply performed by placing a wedge (pillow, roll, blanket) under the patient’s right flank. During a Cesarean section, a right tilting of the bed may be performed in lieu of a wedge. Decreases UVP, decreases UVR. • Fluid boluses of 1–2 L of crystalloid or 0.5–1 L of colloid can be given with neuraxial techniques to offset hypotension caused by the sympathectomy. Preserves UAP. • Vasopressors such as ephedrine (5–10 mg IV bolus) and phenylephrine (50–100 mcg IV bolus) can help maintain maternal BP in the perioperative period. Increases UAP (3). – Historically, phenylephrine was not used to treat maternal hypotension due to concern that alpha-adrenergic effects cause uterine vasoconstriction (increase UVR). Current research shows that UBF is not decreased by a significant amount when using phenylephrine at clinical doses. • Hypertonic uterine dysfunction or uterine tachysystole is defined as >5 contractions in 10 minutes, averaged over a 30-minute window. This can occur with induction of labor and can lead to uteroplacental insufficiency, placental abruption, and uterine rupture. Treatment includes cessation of labor induction medications (e.g., oxytocin) and administration of beta-2 adrenergic receptor agonists. Selective beta-2 adrenergics: – Binding increases intracellular production of cAMP, resulting in decreased calcium levels. This leads to smooth muscle relaxation (myometrial relaxation in the uterus). – Tocolysis can be achieved for ∼48 hours. Desensitization occurs through downregulation of receptors, thus limiting long-term use. – The use of terbutaline as a tocolytic is an off-label use. – Maternal side effects: Tachycardia, palpitations, flushing (related to cross-reactivity of beta-1 receptors) Hyperglycemia (beta-2 stimulation of glucagon release) Hypokalemia (potassium shifts intracellularly) Pulmonary edema Seizures – Fetal side effects: Tachycardia (crosses placenta) – Ritodrine was withdrawn from the market in the US due to side effects (hypotension, maternal and fetal tachycardia, tremors, anxiety, etc.) (4)

EQUATIONS

UBF = (UAP - UVP) / UVR; where UBF is uterine blood flow, UVP is uterine venous pressure, and UVR is uterine vascular resistance.

REFERENCES

1. Palmer SK, Zamudio S, Coffin C, et al. Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy. Obstet Gynecol. 1992;80(6):1000–1006.

2. Macones GA, Hankins GD, Spong CY, et al. The 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring: Update on definitions, interpretation, and research guidelines. Obstet Gynecol. 2008;112:661–666. 3. Mintzer BH, Johnson RF, Paschall RL, et al. The diverse effects of vasopressors on the fetoplacental circulation of the dual perfused human placenta. Anesth Analg. 2010;110(3):857–862. 4. Lam F, Gill P. Beta-agonist tocolytic therapy. Obstet Gynecol Clin North Am. 2005;32(3):457–484.

ADDITIONAL READING

• American Congress of Obstetricians and Gynecologists • Society for Obstetric Anesthesia and Perinatology

See Also (Topic, Algorithm, Electronic Media Element) • Aortocaval compression of pregnancy • Umbilical cord prolapse • Fetal cardiovascular physiology • Uterine rupture • Fetal heart tones

CLINICAL PEARLS

• The anaesthetist can affect UBF with neuraxial blocks and by administering general anesthetics. Maintaining maternal BP at a normal level is imperative to maximize UBF. • Avoidance of hypotension may be achieved by administering a fluid bolus before performing neuraxial anesthetics. Hypotension should be immediately treated by vasopressors. • Evidence of non-reassuring heart rate patterns, often due to uteroplacental insufficiency, is a common indication for Cesarean section. • Terbutaline can help increase UBF if a patient is having hypertonic contractions.

UTERINE RUPTURE Sara C. Nelson, MD Mark Zakowski, MD

BASICS DESCRIPTION

• Uterine rupture is a complete separation of the uterine wall that results in fetal distress and maternal hemorrhage – Incomplete rupture: Peritoneum is intact – Complete rupture: Contents of the uterus enter the peritoneal cavity or broad ligament – Dehiscence: Subclinical, membranous separation of a previous uterine scar or “window" with an intact uterine serosa • Usually occurs in women attempting a vaginal birth after Cesarean section (VBAC)

EPIDEMIOLOGY Prevalence

• No prior uterine scar: 0.05% • Prior uterine rupture: ∼6% – Low transverse Cesarean incision ∼0.7% – Classical or T Cesarean incision ∼7% • Trial of labor after Cesarean delivery (TOLAC) with spontaneous labor: ∼0.5% – TOLAC with non-prostaglandin induction (e.g., oxytocin): ∼0.8% – TOLAC with prostaglandin inductions (e.g., misoprostol): ∼2.5% Morbidity

• TOLAC associated with ∼70% rate of successful VBAC • Successful VBAC after 1 Cesarean delivery (CD) is associated with comparable or lower maternal morbidity than elective repeat CD. • Majority of the maternal morbidity associated with TOLAC occurs when the TOLAC fails and a CD occurs. • Preventing one adverse neonatal outcome from attempted VBAC and uterine rupture is estimated to require 1591 CDs at a cost of $2.4 million. Mortality

• 10–25% of uterine rupture cases result in serious maternal and fetal morbidity or mortality. • Associated with a 10-fold increase in the risk of neonatal mortality

ETIOLOGY/RISK FACTORS

• Prior uterine surgery: CD, myomectomy • Uterine trauma – Indirect trauma: Blunt (seat belt injury), excessive fundal pressure, extension of cervical

laceration – Direct trauma: Penetrating wound, external version, intrauterine manipulation, postpartum curettage • Uterine distention: Grand multiparity, fetal malpresentation, fetal macrosomia • Excess uterine activity: Oxytocin induction, prostaglandin induction • Uterine anomalies: Bicornuate uterus

PREVENTATIVE MEASURES

• General: – Continuous fetal heart rate (FHR) monitoring can facilitate early detection of uterine rupture. – Effective communication between obstetric and anesthesia teams can facilitate early treatment of uterine rupture. • Intrapartum management during TOLAC – Continuous FHR monitoring – Intrauterine pressure catheter (IUPC) versus an external tocometer should be considered. A loss of contractile strength can be a sign of rupture. – Type and screen – Anesthesia consult: Neuraxial analgesia is NOT contraindicated in TOLAC patients and may provide a conduit for rapid surgical anesthesia if an urgent CD is indicated. – American College of Obstetricians and Gynecologists (ACOG) recommends TOLAC be undertaken at a facility capable of immediate CD. If these resources are not immediately available, the patient should be counseled on increased risk (3).

PREOPERATIVE ASSESSMENT • Changes in the FHR: Fetal bradycardia (70% of cases), variable and/or late decelerations (1) • Abdominal pain (7–10%) – Change in the character of pain during TOLAC may be indicative of uterine rupture. – Escalation of epidural dosing requirements may be a surrogate marker of impending uterine rupture. – Epidurals do not mask the pain of uterine rupture and therefore may be used safely in TOLAC (2). • Hemodynamic instability (5–10%) • Vaginal bleeding (3–5%) • Recession of fetal presenting part (<5%)

DIFFERENTIAL DIAGNOSIS

• Non-reassuring FHR: – Fetal bradycardia (HR< 100 bpm): Fetal asphyxia and acidosis; maternal autoimmune disorder (rarely) – Variable decelerations: Umbilical cord compression (i.e., cord prolapse) – Late decelerations: Uteroplacental insufficiency (i.e., placental abruption) – Decreases in variability caused by: Fetal sleep, asphyxia/acidosis, maternal medications (Beta-blockers, opioids, anxiolytics, magnesium, lithium), maternal GA

• Intrapartum abdominal pain – Placental abruption – Hepatic subcapsular hematoma or rupture (associated with HELLP syndrome) – Broad ligament hematoma or rupture – Progression of labor or inadequate analgesia • Intrapartum vaginal bleeding – Placental abruption – Placenta previa

TREATMENT • Emergent CD • General anesthesia is indicated if an epidural is not already present. • Availability of personnel for neonatal resuscitation • Control of uterine bleeding: Uterine repair, uterine arterial ligation, and/or hysterectomy • Aggressive volume resuscitation with crystalloid, colloid, and/or blood products, as indicated. Patients without a prior uterine scar are more likely to need a blood transfusion (fibrous scar edges are less vascular than newly ruptured myometrium). • Consider invasive monitors if the patient is hemodynamically unstable.

FOLLOW-UP Women with a uterine rupture should be counseled on the high risk (6–32% depending on location) of repeat rupture during subsequent pregnancies and should be managed by elective repeat CD before the onset of labor. CLOSED CLAIMS DATA

• The American Society of Anesthesiologists Closed Claims database contains 426 claims associated with obstetric anesthesia since 1990. • 71% of cases of newborn death/brain damage were associated with a non-reassuring FHR and an urgent/emergent CD. – Uterine rupture was present in 9% of the cases of newborn death/brain damage. – In the cases where anesthesia was implicated, causative factors included anesthesia delay, poor communication, and substandard care. • The most common anesthesia-related causes of maternal death/brain damage were general anesthesia with difficult intubation and maternal hemorrhage. – Maternal hemorrhage accounted for 16% of these cases, one of which was due to uterine rupture.

REFERENCES

1. Bucklin BA. Vaginal birth after cesarean delivery. Anesthesiology. 2003;99:1444–1448. 2. Cahill AG, Odibo AO, Allsworth JE, et al. Frequent epidural dosing as a marker for impending uterine rupture in patients who attempt vaginal birth after cesarean delivery.

Am J Obstet Gynecol. 2010; 202:335.e1–e5.

3. Committee on Practice Bulletins-Obstetrics. Vaginal birth after previous cesarean delivery. Obstet Gynecol. 2010;116:450–463.

ADDITIONAL READING

• Davies JM, Posner KL, Lee LA, et al. Liability associated with obstetric anesthesia. Anesthesiology. 2009;110:131–139. • Lydon-Rochelle M, Holt VL, Easterling TR, et al. Risk of uterine rupture during labor among women with a prior cesarean delivery. N Engl J Med. 2001;345:3–8.

See Also (Topic, Algorithm, Electronic Media Element) • Epidural • Vaginal delivery • Fetal heart tracings

CODES ICD9 • 665.00 Rupture of uterus before onset of labor, unspecified as to episode of care or not applicable • 665.10 Rupture of uterus during labor, unspecified as to episode of care or not applicable ICD10 • O71.00 Rupture of uterus before onset of labor, unsp trimester • O71.1 Rupture of uterus during labor

CLINICAL PEARLS

• VBAC is associated with lower maternal morbidity and mortality than elective repeat Cesarean section. The incidence of uterine rupture in patients attempting TOLAC is <1% with 1 prior CD. • Epidural analgesia is not contraindicated in women attempting VBAC and may provide a more expeditious transition to surgical anesthesia if needed. • Close fetal monitoring and the immediate availability of personnel necessary for an emergency CD can reduce morbidity and mortality in patients attempting VBAC. – The most common sign of uterine rupture is fetal bradycardia. • Patients with a history of prior uterine rupture or classical uterine incision are considered high risk for uterine rupture and should not be offered a TOLAC.

V/Q MISMATCHING Joseph Resti, MD Shashank Saxena, MD

BASICS DESCRIPTION

• Diffusion of gases across the alveolar–capillary membrane is a passive process, and is determined by the partial pressure gradient between the alveolar airspace and the pulmonary capillaries (Fick’s principle). • Under conditions of normal diffusion, proper matching of pulmonary ventilation and blood perfusion is essential to proper gas exchange. • Mismatching of ventilation and perfusion, at a global or alveolar level, results in abnormal gas exchange, and can lead to clinically significant hypoxemia as well as hypercarbia. PHYSIOLOGY PRINCIPLES

• Ventilation and perfusion are both measured in units of volume over time (e.g., L/min), and, under normal resting conditions, are roughly equal (4–6 L/min). • At the level of the entire lung. – Alveolar ventilation (VA) is calculated by subtracting the dead space ventilation (VD) from the minute volume (VE): VA = VE - VD.

– Perfusion is defined as right ventricular output; and because the right ventricle is in series with the left ventricle, they are equal in value. • Alveolar–capillary unit: V/Q matching (and mismatching) should be visualized at the level of each alveolar–capillary unit. For example, in one lung ventilation, if only the left lung was ventilated but the left pulmonary artery was cross-clamped, this would leave only the right lung perfused. The overall lung V/Q matching would be equal (in terms of L/min), but at the level of the alveolar–capillary unit, V/Q matching would be zero. • Under normal conditions with proper V/Q matching (e.g., V/Q ratio close to 1.0), alveolar and capillary gases equilibrate (100 mm Hg and 40 mm Hg for O2 and CO2, respectively) by

the end of blood transfer through the unit. – Oxygen: The venous content is 40 mm Hg, and therefore the gradient is roughly 60 mm Hg (100 mm Hg in the alveolar space minus the pressure in the venous space), resulting in a shifting of O2 from the alveolar space to the capillary blood.

– Carbon dioxide: The venous content is 45 mm Hg, and therefore the gradient is roughly 5 mm Hg (venous pressure minus the pressure in the alveolar space, which is roughly 40 mm Hg), resulting in a shift of CO2 from the blood to the alveolar space.

• Regional differences exist for ventilation and perfusion, under normal circumstances. – Ventilation: Dependent regions of the lung are better ventilated compared to nondependent regions. The dependent regions of the lung have a less negative intrapleural pressure, resulting in a smaller transmural gradient and smaller, more compliant alveoli at

FRC. This results in increased ventilation with inspiration. – Perfusion: Dependent lung regions are better perfused compared to nondependent regions. The effects of gravity on the intravascular pressure result in greater distention and recruitment of pulmonary vessels. This leads to decreased resistance and increased flow. – Regional differences are more exaggerated for perfusion compared to ventilation. In the dependent parts of the lung, there is higher perfusion relative to ventilation, resulting in a V/Q ratio of <1.0. In the nondependent areas of the lung, there is more ventilation relative to perfusion, resulting in a V/Q ratio of >1.0 • In units with a V/Q ratio of <1.0, there will be lower O2 tension and higher CO2 tension. The inverse is true in regions of V/Q >1.0. • Physiologic shunt. There is a small amount of blood that normally bypasses the pulmonary circulation and accounts for 2–5% of the cardiac output. This unoxygenated blood is responsible for the normal A-a gradient that is seen in healthy patients.

ANATOMY

• Alveolar–capillary membrane: Extremely thin and diffusion of both O2 and CO2 occur

quickly. CO2 is roughly 20 times more diffusible than O2; however, under normal, resting

conditions, both are fully diffused within 0.25 seconds, even though transit time through the capillary 0.75–1.2 seconds. • Alveoli: Regional differences exist among the alveoli. In the non-dependent region of the lungs, the alveoli are larger and less compliant, resulting in less ventilation. In the dependent region of the lungs, they are smaller and more compliant, resulting in more ventilation. • Pulmonary vasculature: When compared to the systemic vasculature, the pulmonary vasculature is much more compliant (owing to thin walls) and has substantially less smooth muscle, resulting in the unique properties of distensibility and recruitment, important to understanding regional perfusion. DISEASE/PATHOPHYSIOLOGY

• The most common cause of hypoxemia is regional V/Q mismatching. Other etiologies include diffusion limitation, global hypoventilation, decreased inspired O2, and increased shunting.

– When V/Q approaches 0 (i.e., absolute shunt), the PAO2 and PACO2 will equal pulmonary

capillary pressure gradients. – When V/Q approaches infinity (i.e., dead space as in subsegmental pulmonary embolus), the PAO2 and PACO2 will equal the inspired air partial pressures.

– In reality, distribution is not uniform, and ratios range anywhere from 0 (shunt) to ∞ (dead space ventilation). – Relative shunt (0 < V/Q < 1.0) is responsive to oxygen therapy. Etiologies include COPD, mild pulmonary edema, and mild atelectasis. – True shunt (V/Q = 0), or when the shunt fraction is >25%, is not responsive to oxygen therapy. Etiologies include lobar atelectasis, dense pneumonia, severe acute lung injury, and advanced pulmonary edema. • There are multiple etiologies for elevated V/Q (dead space), and they are related to

nonuniform or decreased blood flow throughout the lung. Examples include obstruction of blood flow (pulmonary embolus or thrombus), destruction of vascular beds (emphysema), severe pulmonary hypertension, and pneumothorax. Hypoxia in these diseases will improve with elevated FiO2.

• For each disease process, the lungs have corrective mechanisms to improve V/Q mismatching. – For shunting, the problem lies in the perfusion of unventilated alveoli. Therefore, the lung will undergo hypoxic pulmonary vasoconstriction (HPV), in which the lungs divert blood away from hypoxic alveoli, in an attempt to return V/Q matching closer to one. – For increased V/Q (dead space), the problem is the lack of perfusion to properly ventilated alveoli. The lungs undergo bronchoconstriction in regions of decreased blood flow in an attempt to decrease dead space and return V/Q matching closer to normal. – The goal of both of these mechanisms is to create a “silent unit” in which there is minimal, but equal, amounts of ventilation and perfusion. • Many disease processes affect both ventilation and perfusion, as the anatomy of both the airspace (alveoli) and pulmonary vasculature are very intertwined. – A common example of this is with emphysema. A patient’s disease process with COPD is both lung parenchyma destruction, leading to airway collapse, and airway obstruction. Decreased ventilation results from airway obstruction and decreased perfusion secondary to destruction of the pulmonary vasculature. – ARDS can have multiple etiologies for hypoxia. Its initial insult, lung inflammation, results in decreased ventilation and compensatory hypoxic pulmonary vasoconstriction. However, in this disease process, vasoconstriction is exaggerated, which can result in V/Q mismatching and creation of dead space, worsening the disease process and accentuating the hypoxemia.

PERIOPERATIVE RELEVANCE

• During general anesthesia, there are changes in both lung ventilation and perfusion. – In supine patients under anesthesia, the functional residual capacity is reduced by ∼20%. Obesity can also reduce FRC. With significant decreases in FRC, the closing capacity approaches FRC and small airway closure occurs. This causes areas of low V/Q (shunt) and hence development of atelectasis. Most atelectasis develops in the dependent portions of the lung. Application of a vital capacity maneuver with an inflation pressure of 40 mm Hg for 5–10 seconds has been shown to improve atelectasis. – The application of 10 mm Hg of PEEP may also help to open collapsed lung but higher levels may worsen the shunt. • Perfusion is also affected, as the dependent areas of the lung receive more perfusion compared to the nondependent areas. If increased levels of PEEP are used during mechanical ventilation of patients under anesthesia, it will further alter V/Q matching. The effect of this is two-fold: First, there is decreased preload to the right heart, resulting in decreased cardiac output. Second, there is a redistribution of blood flow to dependent areas of the lungs, resulting in a “dead-space-like” effect in the nondependent regions of the lung. • During general anesthesia with volatile anesthetics, there is a dose-dependent reduction in hypoxic pulmonary vasoconstriction. Although the clinical significance of this is not clear, it

has been shown that this can lead to abnormal perfusion of the atelectatic dependent lung during general anesthesia, leading to shunt physiology. • When using inhaled agents for induction, V/Q mismatching affects the rate of induction. – This is especially important in pulmonary shunt, where there are nonventilated, perfused units. The mixing of normal capillary blood with shunted capillary blood slows the rate of FA/FI, resulting in slower induction speeds. This effect is more pronounced with poorly soluble anesthetics, such as isoflurane and halothane. – Although dead space does not affect the kinetics of inhaled anesthetics to the degree of shunt, decreased cardiac output (e.g., large pulmonary embolus), a possible etiology of dead space, can result in an increased speed of induction with inhaled anesthetics. • Patient positioning can also have an effect on V/Q mismatching. While the prone position will improve V/Q matching (the rationale behind using prone positioning in the treatment of ARDS), the Trendelenburg and lateral positions will often worsen V/Q matching.

REFERENCES

1. Ault ML, Stock MC. Respiratory function. In: Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC, eds. Clinical Anesthesia. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009. 2. arshall BE, Wyche MQ. Hypoxemia during and after anesthesia. Anesthesiology. 1972;37:178–209. 3. Nyren S, Radell P, et al. Lung ventilation and perfusion in prone and supine postures with reference to anesthetized and mechanically ventilated volunteers. Anesthesiology. 2010;112(3):682–687. 4. West JB, Dollery CT. Distribution of blood flow and the pressure-flow relations of the whole lung. J Appl Physiol. 1965;20:175–183.

ADDITIONAL READING

• Levitsky MG. Pulmonary physiology. 6th ed. New York, NY: McGraw-Hill; 2003. • West JB. Respiratory physiology: The essentials. 8th Ed. Philadelphia, PA, Lippincott Williams and Wilkins; 2009.

See Also (Topic, Algorithm, Electronic Media Element) • Shunt • Dead space • Atelectasis

CLINICAL PEARLS

• The most common cause of hypoxemia is regional V/Q mismatching. – Most of these conditions improve with increased FiO2.

– In conditions that do not improve with increasing the FiO2, this should alert the anaesthetist to the possibility of shunt pathology.

• Atelectasis (shunt physiology) will develop in an average of 6% of the lung parenchyma after induction of anesthesia in the supine position. This atelectasis will be evenly distributed in the dependent portions of both lungs. • Vital capacity maneuvers will help to reduce atelectasis in the perioperative period.

VAGINAL DELIVERY Edna Ma, MD

BASICS DESCRIPTION General

• Vaginal delivery describes the birth of a baby through the vaginal canal, in contrast to a Cesarean section. It commences with the onset of labor and ends with the delivery of the placenta. • Modifications and descriptors of the procedure include: – Normal spontaneous vaginal delivery (NSVD) – Induced vaginal devliery (IVD): Use of drugs or manual techniques to begin labor – Assisted vaginal devliery (AVD): Use of instrumentation such as forceps or vacuum extraction – Vaginal birth after Cesarean section (VBAC) Position

• Left uterine displacement (LUD) to prevent aortocaval compression during labor. • Modified Fowler’s position (while actively pushing).

Incision

None (except if an episiotomy is performed) Approximate Time Variable

EBL Expected

∼500–800 mL Hospital Stay

1–3 days on average

Special Equipment for Surgery

• Ultrasound, transvaginal ultrasound • Tocometer/fetal heart tone monitoring • Equipment available for Cesarean sections

EPIDEMIOLOGY Prevalence

• In 2009, 67.1% of all births were vaginal deliveries • In 6 out of 10 vaginal deliveries, an epidural, spinal, or combined spinal/epidural was

performed. Neuraxial anesthesia was increased when a physician delivered the baby compared to a midwife. Additionally, variations exist with region, age (younger more likely to receive), race (Caucasian were more likely), education (advanced education were more than twice as likely).

Mortality

In the US, the Maternal Mortality Ratio is 13.3/100,000 live births in 2006. Leading causes are pregnancy-induced hypertension, hemorrhage, and pulmonary embolism (1). ANESTHETIC GOALS/GUIDING PRINCIPLES

Neuraxial technique provides the benefit of: • A conscious patient with good pain relief • Decreased maternal catecholamines (2) • Improved muscle relaxation (2) • Decreased dystocia (2) • Analgesis in the event of a forceps delivery, episiotomy repair, retained placenta, or emergent Cesarean section • Neonates with higher Apgar scores compared to mothers who received systemic opioid analgesics (3)

PREOPERATIVE ASSESSMENT History

General medical history, medications, allergies, surgical and anesthetic history, parity, and fetal condition (singleton, twins), pregnancy complication (hypertension, gestational diabetes) Signs/Physical Exam

Careful airway examination MEDICATIONS

• Prenatal vitamins, iron • Insulin, antihypertensives in certain conditions

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

CBC (with platelet count), chemistries, coagulation panel; Rh status, blood type

TREATMENT PREOPERATIVE PREPARATION Premedications

• GI prophylaxis

• Anxiolysis is typically avoided

Special Concerns for Informed Consent

Although a mother may elect not to have a neuraxial block, consider meeting and attaining a history and physical (airway examination), as well as consenting her for a possible Cesarean section with the possibility of a neuraxial or general anesthetic in the event of failure to progress, fetal distress, or other emergency. Antibiotics/Common Organisms

In strep-B-positive patients, a penicillin class of antibiotics is usually administered. INTRAOPERATIVE CARE Choice of Anesthesia

• IV analgesia does not typically involve the anaesthetist • Epidural (“laboring epidural”): Typically performed when the patient is 4 cm dilated (however, the American College of Obstetricians and Gynecologists consensus is “in the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labor”). Insertion and catheter placement is below the level of the spinal cord to avoid inadvertent injury (L3, L4, L5); the catheter is typically threaded 4–5 cm in the cephalad direction. The first stage of labor involves pain afferents from dermatomes T10–L1, via the sympathetic uterine, cervical, hypogastric, and aortic plexuses. The second stage of labor involves T10–S4, which includes the pudendal nerve (S2–4). • A spinal (aka saddle block) or combined spinal epidural may also be performed depending upon the proximity of delivery as well as the practitioner’s experience. Monitors

• BP, HR, SpO2 after epidural placement • Fetal heart tones

Induction/Airway Management

• An epidural test dose is often used to recognize unintentional IV or subarachnoid placement of the epidural catheter or needle (e.g., 3 mL of lidocaine 1.5% with epinephrine 1:200,000). If the catheter is in the IV space, a positive test should elicit an increase in the HR of 20 bpm within 1 minute. Some argue that change in maternal HR lack sensitivity, as increases can occur secondary to laboring and contraction pain. If the catheter is in the intrathecal space, a positive test dose could elicit motor blockage at 3–5 minutes. • Inadvertent dural puncture with an epidural needle is estimated to occur ∼1.5% of the time; a postdural puncture headache (PDPH) occurs in 52.1% of these instances (4). When detected, some practitioners thread a catheter into the intrathecal space to avoid another attempt, provide analgesia (at reduced dosages), and decrease the CSF leakage by mechanical obstruction (believed to induce an inflammatory fibrous reaction in the dura, thus facilitating closure of the puncture site after removal of the catheter). • Traumatic epidural placement (blood in needle or catheter) can result from injury to the blood vessels in the connective tissue or epidural plexus, or patient coagulopathy. The practitioner must weigh variables including patient labs (e.g., Platelets, INR, LFTs), co-

existing conditions (e.g., HELLP, obesity, scoliosis), and patient positioning (e.g., Sitting upright or lateral decubitus) before deciding if attempting epidural placement at another level is warranted. • Hypotension may occur after the test dose, bolus, or infusion as a result of a sympatholysis. Minimizing hypotension can be achieved with a fluid bolus prior to epidural activation, or IV vasopressors. Emergency drugs should be immediately available. Other causes of hypotension include aortocaval compression, high/total spinal, anaphylaxis, pitocin overdose. • High or total spinal anesthesia could result after the delivery of an epidural dose of LA into a catheter that is unrecognized in the subarachnoid or subdural space (placed or migrated) or an overdose of LA in the epidural space (rises).

Maintenance

• LUD minimizes aortocaval compression • Continuous labor epidural infusions can consist of a variety of concentrations. Typical solutions include dilute combinations of local anesthetics (bupivacaine, ropivacaine) and opiates (fentanyl, sufentanil; may be omitted if severe itching or nausea). • Patient-controlled epidural anesthesia (PCEA). Utilizes the continuous epidural technique while allowing the parturient to receive demand boluses by pressing a button. The anesthetist sets the basal rate, as well as the bolus dose, with lockout, to avoid overadministration. Compared to a fixed-rate continuous infusion, it provides a flexible approach for maintenance of labor analgesia, reduces LA dosage, has less motor blockade, and improves patient satisfaction. • Local anesthetic toxicity can occur with catheter migration or inadvertent placement into the intravascular space. Early detection and treatment are important for improving outcome. If a patient demonstrates signs of CNS excitation, thiopental, diazepam, or midazolam may prevent convulsions. If convulsions occur, intubation, followed by ACLS, as appropriate, should commence immediately. Prompt Cesarean delivery of the infant may be necessary to restore maternal circulation. Lipid emulsion can be used to treat refractory cardiac arrest from bupivacaine toxicity. • Unilateral anesthesia or “patchy” anesthesia: Can result from a single-orifice catheter; multiorifice catheters provide a more even distribution of LA. Epidural air may be introduced during placement (loss of resistance technique) and prevent LA spread. Connective tissue septa in the epidural space can result in an anatomic barrier to LA spread. Prolonged lateral decubitus positioning can result in analgesia only to the decubitus side. Catheter migration away from the midline may be resolved with slight withdrawal. • Urinary retention is a common side effect of neuraxial anesthesia as a result of blockade of sacral nerve roots. Opioids cause dose-dependent suppression of detrusor muscle contractility and decreased urge sensation via inhibition of sacral parasympathetic nervous system outflow. Thus catheterization (e.g., Foley) is frequently placed after the onset of neuraxial anesthesia. If no urinary catheter is placed, parturients should be regularly examined for bladder distention, especially if they complain of suprapubic pain during contractions. In addition, the differential diagnosis of breakthrough pain should include bladder distention. • A “walking” epidural describes a neuraxial analgesic technique that permits preserved motor

function and safe patient ambulation, typically with opioids. Low-dose LA have the potential to alter proprioception and decrease lower limb motor strength. Ambulation should still occur with assistance. • Active pushing commences when the cervix dilates to 10 cm. The anaesthetist may be called on to deliver a bolus that is quick and does not provide a dense motor block. Drug choices depend upon speed of onset, availability, experience, and comfort with a drug. Options for speedy onset include: Chloroprocaine 3%, mepivacaine with epinephrine, and lidocaine with bicarbonate to hasten onset (typically 1 mL of 8.4% sodium bicarbonate [1 mEq/mL] is added to 10 mL of lidocaine). In addition, LA solution may be diluted with sterile water or normal saline to increase the spread while decreasing the incidence of a motor blockade. When delivery is imminent, avoiding opioids decreases the chance of neonatal respiratory depression.

Extubation/Emergence

Epidural catheter removal is performed after delivery and when hemostasis is assured; it can be left in place during an episiotomy or laceration repair, retained placenta, or bilateral tubal ligation. Careful removal should be performed to ensure that the entire catheter, with tip, is removed intact. Reports of retained catheter tip in the epidural space have been reported and confirmed with imaging. Management depends on the length of the catheter, physical findings (does it emerge from the skin, is it completely subcutaneous), symptoms (radiculopathy), and patient risks (foreign body in a diabetic patient). A neurosurgical consultation is usually appropriate. Leaving the sterile foreign object in situ may be appropriate.

FOLLOW-UP BED ACUITY

• Bed rest until motor strength has fully recovered. • Postoperative check should examine for any residual anesthetic effects, neurosensory loss or weakness, urinary retention, pain at the insertion site, or headache.

Analgesia

NSAIDS or acetaminophen should be adequate for routine NSVD post-partum patients COMPLICATIONS

• PDPH • Epidural hematoma • Transient neurologic symptoms

REFERENCES

1. rimes DA.The morbidity and mortality of pregnancy: Still risky business. Am J Obstet Gynceol. 1994;170(5 Pt 2):1489–1494. 2. yon DS, Knuckles G, Whitaker E, et al. The effect of instituting an elective labor epidural program on the operative delivery rate. Obstet Gynecol. 1997;90:135–141.

3. Reynolds F.Labour analgesia and the baby: Good news is no news. Int J Obstet Anesth. 2011;20(3):267.

4. Choi PT, Galinski SE, Takeuchi L, et al. PDPH is a common complication of neuraxial blockade in parturients: A meta-analysis of obstetric studies. Can J Anaesth. 2003;50:460– 469. See Also (Topic, Algorithm, Electronic Media Element) • Aortocaval compression • Epidural • Combined spinal epidural • Fetal heart tones • Postdural puncture headache (PDPH)

CODES ICD9 650 Normal delivery ICD10 O80 Encounter for full-term uncomplicated delivery

CLINICAL PEARLS

• Airway edema due to vascular engorgement can lead to a difficult endotracheal intubation. One study reports the incidence of failed intubation in obstetric patients as 1:280, compared to 1:2,280 in nonpregnant patients. • The combination of a potentially difficult airway and the desire to have an awake, alert, and cooperative patient, favors neuraxial anesthesia as the primary choice of analgesia.

VALVULAR FUNCTION Siyavash Fooladian, MD, MPH Ryan Crowley, MD

BASICS DESCRIPTION

• The valves of the heart divide it into 4 chambers and facilitate unidirectional, antegrade flow through the heart. Heart valves open passively along a pressure gradient and close due to a reversal in the pressure gradient during different phases of the cardiac cycle. • Their proper function is critical for normal circulation and for the prevention of secondary cardiomyopathy and congestion of other organs. PHYSIOLOGY PRINCIPLES

• The cardiac cycle begins with blood return to the right and left atria from the venae cavae and pulmonary veins, respectively. • Ventricular diastole consists of 2 phases. The first phase, isovolumetric relaxation, takes place after ventricular systole; this phase occurs with all 4 valves in the closed position. Concurrently, blood is accumulating in the atria and when the atrial pressure exceeds ventricular pressures in diastole, the atrioventricular (AV) valves open (marks the second phase): – Passive blood flow from atria to ventricles represents ∼75% of ventricular filling. – Atrial systole, also known as the atrial kick, accounts for the remaining ∼25% of ventricular filling. – The annuli of the AV valves are displaced upward with ventricular filling. – It should be noted that electromechanical diastole begins while blood is being ejected from the aorta; the aortic valve closes when left ventricular pressure decreases below the aortic pressure. • Ventricular systole begins when ventricular volume and pressure increase and results in the closure of the AV valves (R wave on the ECG). – Isovolumetric contraction follows electrical depolarization (via the Purkinje system) and leads to an incremental increase in intraventricular pressure. – Once intraventricular pressures exceed pulmonary artery and aortic pressures, the semilunar valves (pulmonic and aortic valves) open and blood is ejected. ANATOMY

• The heart is a 4-chamber pump with 2 atria and 2 ventricles. • The atria serve as conduits for blood to enter the ventricles and as priming pumps during the late phase of ventricular diastole to fill the ventricle (“atrial kick”). • 2 AV valves (tricuspid valve and mitral valve) separate atria from ventricles. – Tricuspid: Septal, anterior, posterior leaflets – Mitral: Anterior and posterior leaflets

• 2 semilunar valves (pulmonic valve and aortic valve) separate ventricles from the pulmonary artery and aorta, respectively. – Pulmonic: Right, left, anterior leaflets – Aortic: Right, left, posterior (non-coronary) leaflets • Subvalvular apparatus. Chordae tendineae, located in the ventricles, attach papillary muscles to the tricuspid and mitral valves; they are comprised of collagen and elastin. The papillary muscles are relaxed during ventricular diastole and tensed during systole to prevent the leaflets from inverting into the atria when high intraventricular pressures are generated.

DISEASE/PATHOPHYSIOLOGY

• Valvular diseases lead to chronic volume or pressure stress on the atria and ventricles, leading to characteristic responses and remodeling. • Aortic stenosis (AS): Most common valvular abnormality in elderly patients, especially age >70 years. Normal aortic valve area (AVA) is between 2–4 cm2. – Causes: Congenital or acquired active inflammatory process related to aging. Congenital AS: Bicuspid aortic valve is the leading cause of congenital AS and the most common congenital valvular lesion (incidence of 1–2%; higher in males). It results from two of the leaflets fusing during development. Acquired AS: Calcific AS is the most common cause in the adult population. It is a disease of aging, thought to be caused by an active inflammatory process, similar to atherosclerotic heart disease. It leads to progressive calcification and narrowing of anatomically normal aortic valves. Becomes clinically relevant in the eighth or ninth decade of life. – Severe AS: Peak velocity >4 m/sec. Mean gradient >50 mm Hg. Aortic valve area (AVA) <1 cm2. Aortic valve velocity: LV outflow tract velocity ratio >4:1. – Progressive AS creates an increasing pressure gradient across the aortic valve, leading to a relatively fixed cardiac output. Cardiac output is maintained by the development of concentric left ventricular hypertrophy (LVH) with maintained chamber size. This serves to decrease the wall tension (LaPlace’s law: Tension = (change in pressure × radius)/(wall thickness × 2)). LV contractility and ejection fraction are maintained by concentric LVH until late in the disease process. Over time, LV compliance decreases and LV end diastolic pressure (LVEDP) increases. As a consequence, the “atrial kick” may be responsible for up to 40% of ventricular filling. – Symptoms are usually seen only in patients with severe AS. Angina: Results from ischemia due to increased oxygen demand from thickened myocardium and decreased oxygen supply from elevated LVEDP and decreased coronary perfusion pressure. Syncope: Due to exercise-induced vasodilation in the setting of fixed cardiac output, causing decreased cerebral perfusion.

Congestive heart failure (CHF): Develops with the collapse of compensatory mechanisms and rising LVEDP due to the inability of the LV to overcome increasing resistance caused by the narrowed AV orifice. • Aortic insufficiency (AI): Causes include congenital or acquired. – Congenital: Bicuspid AV or aortic root dilatation due to connective tissue disorders (Marfan’s syndrome). – Acquired: Infective endocarditis or type A aortic dissection as a result of trauma or connective tissue disorders (cystic medial necrosis with Marfan’s syndrome). – Chronic AI leads to progressive volume-induced LV dilatation and LVH. Regurgitation across an incompetent AV leads to LV systolic and diastolic volume overload. Increased LV volume leads to high LV wall tension and increased LVEDP in diastole with resultant eccentric LVH (dilated LV with normal or thickened wall). LV compliance and stroke volume increase, but contractility eventually decreases with time. Can lead to secondary mitral valve dilatation/mitral regurgitation (MR) and left atrial dilatation. Dilated aortic orifice, slow heart rate, and increased systemic vascular resistance increase the regurgitant fraction. – Symptoms: Occur after significant cardiomegaly and CHF due to myocardial dysfunction. Dyspnea: Indicates inadequate forward flow and pulmonary vascular congestion, either from progressive heart failure or significant regurgitant fraction during ventricular diastole. Paroxysmal nocturnal dyspnea. Orthopnea. Angina: At risk for myocardial ischemia due to low diastolic root pressure and increased LVEDP. • Mitral stenosis (MS): Normal mitral valve area > 4 cm2; mean gradient <2 mm Hg – Causes are predominantly due to rheumatic heart disease, in a 2:1 female predilection. 75% of MS involves other valvular lesions (one valve or combined). Combined MS/MR in ∼35–40%. Combined MS with aortic valve disease. – MS classifications: Mild: MV area = 1–2 cm2 Severe: MV area <1 cm2, mean gradient >12 mm Hg – MS pathology due to fibrosis/adhesions affects the commissures, cusps, and chords. As MS progresses, the left atrium (LA) develops pressure overload and the LV develops volume underload. An over-distended LA is prone to developing atrial fibrillation. Elevated LA pressures may be transmitted to the pulmonary vasculature, leading to reversible or irreversible pulmonary hypertension. – Signs and symptoms: Become clinically significant/symptomatic in the third or fourth decade of life. LA and pulmonary artery pressure elevation. Left atrial enlargement (LAE).

Atrial fibrillation due to LAE and underlying electrophysiologic changes of the atrial conduction system. LA thrombus formation from chronic atrial fibrillation. Cor pulmonale. Dyspnea due to pulmonary vascular congestion and increased valvular pressure gradient. Fatigue and weakness due to decreased cardiac output. • MR: Can be of either acute or chronic origin. – Acute: Infective endocarditis, ruptured chordae tendineae, or papillary muscle rupture with acute myocardial infarction. – Chronic: Rheumatic heart disease, degenerative diseases (mitral valve prolapse syndrome, Marfan’s syndrome, Ehler–Danlos syndrome), myxomatous degeneration, mitral valve prolapse. – Signs and symptoms: Volume overload leads to LA and LV dilatation, predisposes to atrial fibrillation LV volume increases, LVEDP is normal, and LVEF is high-normal to allow for a normal stroke volume with presence of regurgitant flow.

PERIOPERATIVE RELEVANCE

• Aortic stenosis: “Sinus, slow, full, tight” – Maintain Normal sinus rhythm. The atrial kick contributes to a larger percentage of ventricular filling in AS Slight bradycardia allows adequate time in diastole for ventricular filling (and coronary perfusion) as well as in systole during each cycle to eject blood through the stenosed valve Adequate intravascular volume/preload Afterload to promote coronary perfusion Contractility to overcome the high pressure gradient across the aortic valve and promote systemic ejection – Avoid Significant bradycardia (decreases cardiac output) Tachycardia (decreases diastolic time and coronary perfusion, leading to ischemia) • Aortic insufficiency: “Fast, full, forward” – Maintain A modest tachycardia to decrease ventricular volumes and minimize regurgitant time Adequate intravascular volume/preload to promote forward flow Decreased afterload to promote forward flow Contractility to promote forward flow • Mitral stenosis: “Sinus, slow, full, tight” – Maintain Normal sinus rhythm in order for the atrial kick to be effective in LV filling. Cardiovert early if new onset atrial fibrillation or atrial flutter A slower heart rate allows for adequate time in diastole for ventricular filling Adequate intravascular volume/preload Afterload

– Avoid: Increases in pulmonary vascular resistance (hypoxemia, hypercarbia, acidosis) in order to minimize worsening of any existing right heart failure. • Mitral regurgitation: “Fast, full, forward” – Maintain Modest tachycardia to decrease ventricular volumes and minimize regurgitatnt time Adequate intravascular volume/preload to supply a dilated LV Decreased afterload to enhance forward flow and decrease regurgitation Contractility; may require inotropic agents that concurrently decrease afterload (milrinone or dobutamine) – Avoid: Increases in pulmonary vascular resistance (hypoxemia, hypercarbia, acidosis) in order to minimize worsening of any existing right heart failure.

REFERENCES

1. Bonow R, Carabello B, Chatterjee K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2006;48:e1–e148. 2. Foster E. Mitral regurgitation due to degenerative mitral-valve disease. N Engl J Med. 2010;363:156–165. 3. Mittnacht AJ, Fanshawe M, Konstadt S. Anesthetic considerations in the patient with valvular heart disease undergoing noncardiac surgery. Semin Cardiothorac Vasc Anesth. 2008;12(1):33–59. 4. Schoen, FJ. Cardiac valves and valvular pathology: Update on function, disease, repair, and replacement. Cardiovasc Pathol. 2005;14(4): 189–194. See Also (Topic, Algorithm, Electronic Media Element) • Aortic stenosis • Aortic regurgitation • Mitral stenosis • Mitral regurgitation • Transesophageal echocardiography • Pressure volume loops

CLINICAL PEARLS

• AS is the most common valvular abnormality. • MS is primarily a sequela of rheumatic heart disease. • Regurgitant valvular lesions: “Fast, full, forward". • Stenotic valvular lesions: “Sinus, slow, full, tight".

VASCULAR COMPLIANCE Viachaslau Barodka, MD

BASICS DESCRIPTION

• Vascular compliance is the ability of a vessel to distend and increase volume with increasing transmural pressure (inside − outside pressure): C = ΔV ΔP, where ΔV is the change in volume and ΔP is the change in pressure. • Capacitance is the amount of volume stored at a given pressure. • Distensibility is compliance divided by the initial volume. • Arterial compliance is an index of the elasticity of large arteries such as the aorta or the carotid artery. It is used as an indication of arterial stiffening. • Elasticity or vascular stiffness is the reciprocal of compliance. For arterial vasculature, the term stiffness is more commonly used. • The stroke volume and pulse pressure can provide an estimate of arterial compliance or stiffness. Clinically, pulse wave velocity, the speed with which a pulse travels along an artery, has been shown to be the best representative of arterial stiffness. • Vascular compliance is decreased (stiffness is increased) with: – Advanced age – Diabetes – Kidney failure – Acute and chronic smoking – Essential hypertension PHYSIOLOGY PRINCIPLES

• Veins: – >70% of the body’s blood volume is stored in veins. They are high capacitance vessels and can store large amounts of blood at low pressures. – At low venous pressures, the compliance of a vein is 10–20 times greater than an artery. At high pressures (e.g., when a peripheral vein is used as a graft in CABG surgery) venous compliance becomes similar to arterial compliance. – Venous compliance impacts the cardiovascular system by regulating preload. • In arteries, where blood flow is pulsatile, the compliance is estimated as a change in radius, diameter, flow, or cross-sectional area for a given change in pulse pressure. Factors include: – Elastin and collagen: Elastin fibers bestow “cushioning” and hence increase compliance (decrease stiffness). The central arteries (aorta and carotids) are rich in elastin and are thus able to stretch and readily accomodate the stroke volume. Collagen fibers provide structural support and do not stretch. – Distending pressure: Due to changes in capacitance, blood vessel compliance is not static over varying pressures. At higher pressures, the capacity of the vessel decreases (less room) as does the compliance; this is demonstrated by a flat slope in the volume versus

pressure curve. At lower pressures, the capacity of the vessel increases (room for more) as does the compliance; this is demonstrated by a steep slope. – Rate of change: When vessels are extended rapidly, they are stiffer than when they are extended slowly. – BP: Both compliance and stiffness are directly and indirectly influenced by all factors influencing BP (vasomotor tone, circulating blood volume, stroke volume, heart rate and cardiac contractility, supine vs. upright position). Vascular tone has a significant effect; relaxation of vascular smooth muscle increases compliance, whereas contraction decreases it. Stiff arteries have poor compliance and a decreased ability to accommodate the incoming stroke volume. Diurnal variation: Like BP, compliance and stiffness show a diurnal variation, with increased stiffness during sleep. – Age: Young elastic arteries have good distensibility (high compliance, and low stiffness). With age, vessel distensibility/compliance decreases and stiffness increases from: Elastin fragmentation and degradation, collagen increases, wall thickening, atherosclerosis development, and lumen dilation. • Kinetic energy: Each stroke volume contributes only 5% to the total blood flow. 95% of the energy is potential energy stored in the distended conduit arteries. Because of the cushioning effect, most of the energy stored in BP pulsations is transformed and dissipated in the major arteries, such that eventually, blood flow is almost laminar and steady through peripheral arterioles and capillaries. • Pulse wave velocity measurements: Distance is measured at 2 separate points along the arterial tree, usually the carotid and femoral arteries or the carotid and radial arteries. The time interval is determined by measuring the time between the EKG R wave and the start or peak of the pulse wave at each of the arterial sites of measurement to derive the “time elapsed.” – Pulse wave velocity in a young person is approximately 4–6 m/s; it increases to 10 m/s by the age of 65 years and continues to increase with advancing age. • Commercially available devices to measure arterial stiffness: Several are available. Most derive their measurements from peripherally acquired waveforms by using tonometry. Central pressure waveforms are then extrapolated by mathematical modeling based on transfer function of waveforms.

ANATOMY

• The vascular wall is composed of 3 layers: – Intima: Innermost layer; contains a single layer of endothelium. – Media: Central layer; thickest and rich in vascular smooth muscle cells and elastin. – Adventitia: Outermost layer; composed mostly of collagen and provides mechanical strength to the vascular wall. • Aorta: The proximal parts of the aorta are more elastic than the distal vasculature and contain a relatively greater proportion of elastin compared to collagen. The mean pressure decreases by only 1–2 mm Hg between the ascending aorta and a peripheral artery, indicating an excellent cushioning and conduit function. The cushioning effect stores the energy of incoming blood during systole and gives it back to promote forward flow in

diastole.

DISEASE/PATHOPHYSIOLOGY

• Loss of compliance or increased vascular stiffness is manifested as: – Increased systolic BP – Decreased diastolic BP – Increased pulse pressure – No change in mean arterial pressure – Increased pulse wave velocity – Decreased blood volume at a given pressure • Concomitant organ effects. – Loss of compliance with vascular stiffening exposes organs to high pulsatile pressures that lead to arterial remodeling and microcirculatory damage in the brain and kidney. – Ventricular hypertrophy: Chronic decreases in vascular compliance manifest as an increased afterload to the left ventricle. To offset the increased workload of the heart, the ventricle can become hypertrophic. However, this increases the oxygen demand (more muscular) while decreasing the oxygen supply (thicker muscle makes capillary perfusion to the endocardium more difficult). This can progress to diastolic dysfunction and heart failure. – Vascular–ventricular coupling of stiffer vessels with a stiffer heart has an overall deleterious effect on pressure and flow regulation (including coronary blood flow), resulting in decreased cardiovascular reserve and a lower threshold for the development of cardiovascular disease. – It is now generally accepted that increased arterial stiffness is a sensitive, early, noninvasive measure of vascular disease. • Sclerosis: Arteriosclerosis describes the loss of compliance and stiffening of major conduit arteries; whereas atherosclerosis describes the formation of atherosclerotic plaques in the intima. • Aging – There is progressive thickening of the arterial wall even in the absence of atherosclerotic disease. This results from intimal thickening and sclerotic changes in the media and adventitia (progressive fragmentation of elastin fibers, decrease in the number of VSMC, and accumulation of collagen). – The pulse wave velocity can increase 2-fold between the ages of 20 and 80, a change that corresponds to a 4-fold decrease in distensibility or compliance of the aorta. • Cross-linking of extracellular matrix proteins: Advanced glycation end-products and increased activity of the enzyme transglutaminase 2 are responsible for irreversible crosslink formation between structural proteins. This leads to decreased compliance of vessels. • Genetics: Data from the Framingham Heart Study have shown that aortic stiffness is a heritable trait. Genetic polymorphisms for the angiotensin receptor, metalloproteinases, fibrillin-1, and the endothelin pathway have been reported to influence central vascular stiffness.

PERIOPERATIVE RELEVANCE

• Indices of reduced vascular compliance, such as a widened pulse pressures were shown to be

an independent predictor of renal, neurologic, and cardiovascular events in patients undergoing cardiac surgery. • Hemodynamics: Decreased arterial compliance requires the heart to generate higher pressure to eject the same stroke volume. Over time, the increased myocardial work can cause left ventricular hypertrophy, diastolic dysfunction, and eventually heart failure. • In the setting of decreased vascular compliance and increased vascular stiffness, autoregulation in the brain and kidney may become impaired or lower autoregulatory limits may develop. Organ hypoperfusion may result when such individuals are exposed to what otherwise might be considered an “acceptable” BP. Hence the goal is to maintain the MAPs at a higher level.

EQUATIONS •

Where C is compliance, ΔV = change in volume and; ΔP = change in pressure •

Where E is elastance, ΔV = change in volume and; ΔP = change in pressure

REFERENCES

1. Barodka VM, Joshi BL, Berkowitz DE, et al. Implications of vascular aging. Anesth Analg. 2011;112(5):1048–1060. 2. Steppan J, Barodka V, Berkowitz DE, et al. Vascular stiffness and increased pulse pressure in the aging cardiovascular system. Card Res Practice. 2011. 3. Safar ME. Arterial Aging – hemodynamic changes and therapeutic options. Nat Rev Cardiol. 2010;7(8):442–449.

ADDITIONAL READING

• Nichols WW, O’Rourke MF. McDonald’s Blood Flow in Arteries. 5th ed. Oxford University Press; 2005.

See Also (Topic, Algorithm, Electronic Media Element) • Mean arterial pressure • Systemic vascular resistance • Afterload

CLINICAL PEARLS

• Reductions in vascular stiffness are associated with reductions in cardiovascular risk. • Regular physical exercise has been reported to slow down the increases in arterial stiffness with age and improve arterial compliance. • Nitrates, angiotensin pathway blockers, and calcium antagonist, in contrast to diuretics and beta-blocker–based therapies, are preferentially used to decrease central arterial stiffness and improve patient outcomes independent of BP reduction.

• Stiffened arteries require a greater amount of force to cause them to expand and take up the blood ejected from the heart. This increased force requirement is provided by the heart, which begins to contract harder to accommodate the artery. Over time, this increased load causes left ventricular hypertrophy and, potentially, left ventricular failure. Additionally, increased time is required for systole, at the expense of diastolic time (recall that perfusion to the left ventricle only occurs during diastole). Thus, the hypertrophic heart has an increased oxygen demand, but is also more prone to decreased delivery, thereby increasing the incidence of cardiac damage.

VENOUS AIR EMBOLISM Nina Singh-Radcliff, MD

BASICS DESCRIPTION

Venous air embolism (VAE) describes the entrapment of air or gas from the operative field or other communication with the environment into the vasculature, resulting in mechanical obstruction and secondary chemical and inflammatory mediators that impair gas exchange. EPIDEMIOLOGY Prevalence

• Difficult to assess accurately due to the variable sensitivity of current detection methods and its subclinical presence • Posterior fossa surgery: 80% • OB-gynecologic surgeries: 11–97% • Laparoscopies: 69% • Orthopedic surgeries: 57% • Presence of a patent foramen ovale: 20–35% • Severe lung trauma: 4–14% • Cervical laminectomy: 10% • Insertion/removal of central line catheters with optimal positioning, technique: 0.13%

Morbidity/Mortality

Proportional to the volume and rate of air entry, patient position, and entry site, as well as underlying cardiac disease ETIOLOGY/RISK FACTORS

• Operative site above the heart (5 cm): – Sitting craniotomies, posterior fossa procedures, craniosynostosis repair, upright posterior cervical surgery, radical neck dissection, thyroidectomy. – Positioning (Trendelenburg, lateral decubitus, uterine displacement). THA, lateral decubitus thoracotomies, obstetric and genitourinary procedures • Mechanical insufflations – Laparoscopy, gastrointestinal endoscopy • Blunt, penetrating chest trauma • Vascular access – Central, peripheral, arterial lines – TPN, interventional radiology • Pressure infusions/fluid irrigation – Shoulder arthroscopy – Rapid infusers

• Scuba diving, aviators, astronauts, and positive pressure ventilation

PHYSIOLOGY/PATHOPHYSIOLOGY

• Two requisites: Direct communication between the air source and vasculature, plus a pressure gradient favoring the passage of air into the circulation. • Operative site >5 cm from the heart. Venous pressure exceeds atmospheric pressure, except when above the level of the heart. An injury to the vein allows air entry that travels to the right heart and then the lungs. This is increased with large, noncompressed venous channels, such as dural sinuses in neurosurgery. • Mechanical insufflations: CO2 enters inadvertent open vascular channels from surgical

manipulation. It is 20 times more dissolvable in blood than oxygen and significantly more than nitrogen, which may explain why, despite its high occurrence, it is often subclinical. • Pressure infusions/fluid irrigation: When air is accidentally introduced into the system, it can subsequently be “driven” by the fluid pressure into veins or cancellous bony surface. • Central vascular access: The equipment allows direct access to the vein during insertion or removal and when the patient is spontaneously ventilating, a negative pressure breath can provide the driving force. Inadvertent introduction of air into arterial lines, peripheral IVs, and other access is also a cause. • Clinical manifestations result from mechanical and chemical pathophysiologic mechanisms, with the key factors being volume and rate of entrainment. The alveolar/capillary interface is capable of absorbing and exhaling gas from the circulation; when it occurs over a slow period, it is capable of withstanding large quantities. When this mechanism is overwhelmed (large amount and/or fast rate), symptoms result. • Mechanical obstruction results from a gas-airlock in the right ventricular outflow tract (RVOT) or pulmonary circulation (V/Q mismatch: dead space being ventilated, but not perfused). Partial RVOT obstruction causes right heart strain (increased CVP, JVD; peaked P waves), decreased CO (increased wedge pressure; reduced MVO2, BP), with resultant

cardiac and cerebral ischemia (tachyarrhythmias, ST changes). Complete RVOT obstruction results in heart failure, CV collapse, and possible death. • Chemical pathways: Air in the right heart and pulmonary circulation trigger secondary injury from the activation of complement and inflammatory pathways (endothelin 1, platelet activator inhibitor, fibrin, neutrophils, lipid droplets, etc.). These result in pulmonary vasoconstriction/hypertension, microvascular permeability, platelet aggregation, noncardiogenic pulmonary edema, bronchoconstriction, and subsequent V/Q mismatch (shunting: Ventilation hindered, perfusion continues and returns non-oxygenated blood to the left heart circulation.). • Paradoxical air embolism: The presence of a patent foramen ovale (25–30% of the population) allows for a gas bubble to travel from the right-to-left side of the heart (bypasses lungs, direct delivery to cerebral and coronary arteries, resulting in ischemia or infarct).

PREVENTATIVE MEASURES

• Patient positioning: The sitting position is utilized to provide adequate surgical conditions (visualization, reduced bleeding). Maintain a high level of suspicion, reduce the driving

pressure gradient, and implement appropriate monitoring. Alternatives include the prone and park bench position (strongly consider with documented PFO). • Hydration: Increases CVP, and reduces the negative pressure gradient at the level of insertion. Studies have suggested maintaining the CVP at 10–15 cm H20. Consider zeroing

the transducer at the level of the right atrium, and then elevating it to the surgical site to determine if a negative pressure gradient exists. • Central line placement and removal should be performed in the Trendelenburg position (increases venous pressure at access site by gravity). During insertion and removal, consider occlusion of the needle hub/catheter, avoidance of deep inspiration when the patient is SV (avoids negative pressure/suction effect), and PEEP when the patient is being PPV. When Trendelenburg is contraindicated (increased ICP), consider temporary positioning during insertion of the guidewire or catheter, or raising the legs to increase venous return and pressure in the right atrium. • PEEP: Theoretically, it increases intrathoracic pressure, thus reducing air entrainment into the surgical site (note: In patients with increased ICP, the goal is to reduce intrathoracic pressure to facilitate venous drainage of blood into the right atrium). Controversial, because it may increase the risk of paradoxical air embolism (increased intrathoracic, pulmonary vasculature pressures, facilitates flow through the PFO) and may exacerbate negative pressure when there is a sudden release. Consider PEEP when oxygenation needs to be improved, rather than to prevent a VAE. • Avoidance of nitrous oxide is suggested particularly for sitting craniotomies. However, studies have not shown an increased incidence of VAE.

PREOPERATIVE ASSESSMENT • Spectrum of effects is dependent on rate and volume of air entrainment. • Signs and symptoms – Awake patient: Acute dyspnea, continuous cough, gasp reflex, lightheadedness, vertigo. – Pulmonary: Wheezing, bronchoconstriction, pulmonary hypertension, rales, tachypnea. – Cardiac: Dysrhythmias, peaked P waves, ST segment changes, JVD, right heart failure, low BP, CV collapse. – Cerebral: AMS, seizures, ischemia due to hypoperfusion or air emboli in the cerebral circulation from a patent foramen ovale. – Transesophageal echocardiogram: Permits detection of macroemboli and microemboli, as well as paradoxical cerebral complications. Most sensitive (can detect as little as 0.02 mL/kg). Limited by cost, invasiveness, and over-sensitivity (not clinically relevant levels). • Precordial Doppler ultrasound: Audible detection of RVOT blood flow (normal flow produces a ‘washing machine’ turbulent sound; VAE results in an erratic, high-pitched swishing roar, or “mill wheel” sound). Placed along the right heart border (second to fourth intercostals space); confirm position with “bubble test” (1 mL air + 9 mL saline delivered fast push into the central or peripheral access). Most sensitive non-invasive monitor (0.05 mL/kg or 0.25 mL of air). Limited by obesity, prone or lateral position, and concurrent use of cautery. • Pulmonary artery catheter: VAE causes mechanical obstruction and decreased CO

(obstruction in pulmonary artery results in increased PA, RV, and CV pressures; reduced CO seen as reduced MvO2; and LV ischemia can increase PAOP). Additionally, small amounts of

air may be aspirated from the lumens. Limited by being relatively insensitive (requires at least 0.25 mL/kg air), invasive (not justified as monitor unless patient has qualifying comorbidities), and minimal ability to aspirate air. • Transcranial Doppler: Useful in detecting cerebral air in patients with PFO. High sensitivity (increased with Valsalva maneuver), non-invasive • ETN2: Air is ∼75% nitrogen. If utilizing 100% O2 in the circuit, the detection of N2 in expiratory gas suggests VAE. It is the most sensitive gas-sensing method (can detect as little as 0.04% N2 and 30–90 seconds earlier than ETCO2). However, it is not routinely available

on all monitors. • ETCO2: Reduced CO2 in exhaled air results from dead space (CO2 continues to increase in

the blood, but cannot be delivered or excreted via the alveoli). Moderate sensitivity (change of 2 mm Hg may indicate VAE). Standard ASA monitor, but lacks specificity and reliability. Hypotension also produces “dead space” effect. Consider adjusting the “low” level alarm to optimize detection. • O2 saturation: Late finding. See Table

DIFFERENTIAL DIAGNOSIS • Acute coronary syndrome • Cardiogenic shock • Cerebrovascular accidents

TREATMENT • Prevention • Stop further air entry. Inform surgeon, cover surgical field with saline-soaked dressings, assess and eliminate entry site (cautery, bone wax), increase CVP with fluid hydration (reduces pressure gradient). Tilt OR table (Trendelenburg, reverse Trendelenburg, lateral decubitus) to place the likely source of air entry below the level of the heart (eliminate the negative pressure gradient). In neurosurgical procedures, consider transient jugular venous compression (increases venous pressure, helps identify open dural sinuses from retrograde flow; however, this increases ICP, and may compress the carotid artery with resultant decreases in the CPP). • Reduce volume of entrained air: Aspirate air from the right atrium via the central line port, if present. Controversial whether to place after VAE occurrence (distracts from other treatment, capable of removing only 15–20 mL). If surgical procedure with a high risk for VAE, consider a multiorifice catheter. • Reduce embolic obstruction: Strong, effective chest compressions. Consider positioning the patient in the partial left lateral decubitus position (Durant’s maneuver) to relieve airlock in the right heart (no data to support this and will interference with chest compressions).

• Hemodynamic support/supportive measures: High-flow oxygen (FiO2 1.0; may reduce

embolism volume by eliminating N2; increases oxygen delivery to ischemic areas), CPR

(defibrillation and compressions) provides blood flow and oxygenation, particularly in pulseless electrical activity. Inotropic support to the right ventricle (failure from increased pulmonary circulation afterload) can be achieved with dobutamine, ephedrine, epinephrine, and norepinephrine. • Hyperbaric oxygen therapy: Utilized for decompression therapy, (reduces the size of air bubbles by creating a high O2 diffusion gradient that accelerates N2 resorption; FiO2 1.0, at a partial pressure of 2000 mm Hg). Typically a 5-hour session for the initial treatment, followed by sessions 1–2 times a day for symptom relief. • Heparin: Prophylactic administration may reduce the severity of VAE. • Steroids: May reduce secondary inflammatory pathways; however, it does not have any effect on cytotoxic brain edema seen in VAE. • Lidocaine: Prophylactic administration may reduce the effect of VAE on the brain by decreasing brain edema. • Experimental therapies: Fluorocarbon derivatives enhance the reabsorption of bubbles and enhance the solubility of gases in the blood. Fluorocarbon FP-43 enhances O2, CO2, and N2 solubility to 100,000 times that of plasma. Human data lacking at this time.

FOLLOW-UP • If hemodynamic stability is recovered, may consider continuing with surgical procedure • Consider continued intubation with positive pressure ventilation, vasopressors • Consider central line placement for monitoring and therapy, if not already in place

CLOSED CLAIMS DATA

Air embolism comprised 8% (10/140) of IV catheter claims (All claims n = 6881). • Deaths: N = 4 • Claims resulting in payment: 100% • Payment range: $20,800–$3,302,700

REFERENCES

1. Mirski MA, Lele AV, Lunei Fitzsimmons, et al. Diagnosis and treatment of vascular air embolism. Anesthesiology. 2007;106:164–177. 2. almon SC, Moore LE, Lundberg J, et al. Venous air embolism: A review. J Clin Anesth. 1997;9:251–257. 3. Muth CM, Shank ES. Primary care: Gas embolism. N Engl J Med. 2000;342:476–482. 4. Souders JE. Pulmonary air embolism. J Clin Monit Comput. 2000;16:375–383. 5. iebler R, Kollenberg B, Pohlen G, et al. Effect of positive end-expiratory pressure on the incidence of venous air embolism and on the cardiovascular response to the sitting position during neurosurgery. Br J Anaesth. 1998;80:30–35.

6. uman KJ, Spiess BD, McCarthy RJ, et al. Cardiorespiratory effects of venous air embolism in dogs receiving a perfluorocarbon emulsion. J Neurosurg. 1986;65:238–244. See Also (Topic, Algorithm, Electronic Media Element) • Dead space • Ventilation and perfusion mismatching • Central line placement • Laparoscopy

CODES ICD9

• 673.00 Obstetrical air embolism, unspecified as to episode of care or not applicable • 958.0 Air embolism • 999.1 Air embolism as a complication of medical care, not elsewhere classified ICD10 • T79.0XXA Air embolism (traumatic), initial encounter • T80.0XXA Air embolism fol infusion, tranfs and theraputc inject, init • O88.019 Air embolism in pregnancy, unspecified trimester

CLINICAL PEARLS

• Two requirements: Direct communication between air source and vasculature PLUS a driving pressure gradient. • Pathophysiology is composed of mechanical obstruction and secondary insult due to chemical and inflammatory mediators. • Treatment should consist of prevention, prevention, prevention. Followed by stopping further entrainment, removal of entrained air, and hemodynamic support. • Iatrogenic and preventable: New technologies have expanded the realm of procedures where the patient is at risk; thus, it requires a high index of suspicion.

VENTILATOR-ASSOCIATED PNEUMONIA Praveen Kalra, MBBS, MD, FCCP

BASICS DESCRIPTION

• Ventilator-associated pneumonia (VAP) is a nosocomial pneumonia that occurs after 48 hours of mechanical ventilation via an endotracheal tube (ETT) or tracheostomy tube. • Clinical pulmonary infection score (CPIS) utilizes clinical, radiographic, physiologic, and microbiologic data. CPIS assigns a numerical score to the presence (or absence) of (1,5): – A new or progressive pulmonary infiltrate on chest radiograph – Fever >38.3°C – Leukocytosis or leukopenia – Purulent tracheobronchial secretions – Evidence exists that a score >6 correlates with VAP. – However, because these findings are non-specific, they can lead to inappropriate antibiotic treatment of non-infectious processes and also correlate poorly with microbiologic cultures. • VAP is the most common nosocomial infection in the ICU, extends ICU length of stay, increases admission cost significantly, and carries a significant morbidity and mortality. EPIDEMIOLOGY Prevalence

• Estimated incidence ranges from 9–28% of all intubated patients (5). • Incidence is greatest early in the course of hospital stay; 50% of all cases occur within the first 4 days of mechanical ventilation (1). • Risk has been found to be 3% per day during the first 5 days of ventilation, 2% per day during Days 5–10, and 1% per day after Day 10 (1,5). • Most common pathogens: Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, and Acinetobacter species; infections with methicillin-resistant Staphylococcus aureus are becoming more common in the US.

Morbidity

• Prolongs ICU stay by an average of 4.3 days; prolongs cost by ∼$40,000 (1) • Improved prognosis with early onset (within 96 hours of the start of ventilation); more likely to be infected with antibiotic-sensitive bacteria • Worsened prognosis with late onset (after 96 hours of mechanical ventilation); more likely to be infected with multidrug-resistant bacteria and have greater mortality Mortality

Overall: 25–50%; influenced by the type of infecting organism (P. aeruginosa and Acinetobacter species), underlying comorbidities (bacteremia), severity of host response, and

treatment with ineffective antibiotic therapy (2)

ETIOLOGY/RISK FACTORS

• Endotracheal intubation; no difference between oral and nasal intubations (4,5) • Reintubation (particularly following unplanned or failed extubation); likely due to aspiration of infected upper airway secretions while reintubating • Critically ill, APACHE II score >16 • Supine position • Nasogastric and enteral feeding tubes; promotes gastroesophageal disease • H2 blocker or antacid therapy • Acute or chronic lung disease, cigarette smoking • Age >60 years • Impaired mental status or excessive sedation • Witnessed aspiration • Paralytic agents • Continuous or over-sedation • Prolonged antibiotic use • Frequent ventilator circuit changes • Impaired swallowing reflex

PHYSIOLOGY/PATHOPHYSIOLOGY

• In health, the lungs are sterile. There are numerous defense mechanisms in place to protect against infection: Antimicrobial agents in saliva (non-immune), cough reflexes, mucociliary clearance, cell-mediated immunity (alveolar macrophages, neutrophils), and humoral immunity. • Intubated patients have accumulations of contaminated secretions in the subglottic space and above the ETT cuff (from the oropharynx), as well as impaired cough reflexes and mucociliary clearance, combined with injured tracheal epithelial cell. • The mechanism of micro-aspiration can result from increased hydrostatic pressure of subglottic secretions above the ETT cuff as well as aerosolization of bacteria within the respiratory tubing. • Critically ill patients can have dysfunctional or overwhelmed immune systems (impaired neutrophils, structural and functional alveolar changes). Thus, gross or micro-aspiration of oropharyngeal organisms into the distal bronchi can be followed by bacterial proliferation and pneumonia. • Less commonly, sinus and dental organisms or direct contamination from bacteremia can result in VAP. • Stress ulcer prophylaxis, a commonly implemented technique in critically ill patients, alkalinizes gastric fluid and may favor bacterial overgrowth with anaerobic gram-negative bacteria. Gastroesophageal reflux and aspiration around the ETT cuff may therefore contribute to VAP. This is controversial and studies have yielded mixed results. • Oral flora can also shift toward more aerobic gram-negative bacilli and Staphylococcus species in critical illness or secondary to antibiotic exposure • ETTs also serve as a reservoir for microbes by providing them a surface to adhere to by forming a BIOFILM.

PREVENTATIVE MEASURES

• VAP can be somewhat difficult to diagnose and also carries a significant increase in morbidity and mortality; therefore, preventive measures are key. They consist of techniques and measures as well as technology and equipment. • Maintain the patient in a semi-upright position (30–45°), particularly when receiving enteral nutrition. There is some data to support the lateral position to eliminate gravitational forces (2,3). • Daily sedation interruption to screen for patient readiness for extubation (2). • Risk assessment for stress ulcer prophylaxis; should not be automatically instituted. If necessary, consider sucralfate, as there is some evidence to suggest a reduced incidence of VAP (2). • Decontamination of the oropharynx by oral antiseptics (chlorhexidine) may reduce incidence. Oral application of antibiotics has not shown success (2,3). • Digestive decontamination may be considered in the presence of multidrug-resistant pathogens (2,3). • Hand disinfection by the healthcare team (2,3). • Continuous aspiration of subglottic secretions (CASS) can decrease bacterial colonization and requires a specialized ETT (2,3). • Noninvasive ventilation avoids intubation and mechanical ventilation (2,3). • Silver-coated ETT provides a highly effective antimicrobial substance that can prevent BIOFILM formation and subsequent infection (2,3). • Ultrathin cuffs (high volume, low pressure cuff) can prevent formation of folds, provide better sealing, and reduce VAP (2,3). • Early tracheostomy (<7 days after translaryngeal intubation) in VAP prevention remains controversial (2,3). • The CDC recommends that ventilator circuits be changed no more than every 48 hours.

PREOPERATIVE ASSESSMENT • History, symptoms, signs, physical examination – The non-specific nature of signs and symptoms of VAP makes diagnosis difficult. – Increased respiratory rate, FiO2 demand, hypoxia. – Temperature: >38.3°C • Diagnostic procedures – Chest radiograph: The presence of a new or progressive pulmonary infiltrate – White blood cell count: Leukocytosis – PaO2: Decreases

– Microbial sputum smear/Gram stain – Cultures: Sputum, tracheal, or lower respiratory tract samples. Much controversy exists over whether sputum and tracheal aspirates or invasive lower respiratory tract samples improve diagnostic and therapeutic methods. Sputum and tracheal aspirates may yield colonizing organisms from the trachea and ETT and are associated with higher antibiotic use. However, invasive methods have risk, require special equipment, and increase cost

but may not improve outcome or reduce mortality. Quantitative cultures may help differentiate colonization from infectious bacterial agents. – Triggering receptor expressed on myeloid cells (TREM-1) is a member of the immunoglobulin superfamily and is involved in the acute inflammatory response. Neutrophils express high levels of TREM-1 on exposure to infected tissues. Shown to have a sensitivity of 98% and specificity of 90%.

DIFFERENTIAL DIAGNOSIS • Aspiration pneumonitis • Atelectasis • Pulmonary embolism • ARDS • Drug reaction • Pulmonary hemorrhage • Lung contusion • Radiation pneumonitis • Infiltrative tumor

TREATMENT • Prompt and appropriate antibiotic treatment significantly improves survival in patients with VAP. Since culture results can be delayed for several days, the Gram stain and clinical suspicion (common organisms in the hospital) may need to guide initial therapy (4). • Empirical therapy for patients suspected of having multidrug-resistant pathogens should include coverage for gram-negative bacilli and Pseudomonas until sputum culture sensitivity data is available. Therapy can be narrowed once culture results arrive (4). • Evidence-based data supports limiting the total duration of antibiotics therapy to 7 days in responders.

FOLLOW-UP Some evidence to suggest that serial quantitative microbial cultures aid in assessing newer airway colonization.

REFERENCES

1. frati S, Deutsch I. Ventilator associated pneumonia: Current status and future recommendations. J Clin Monit Comput. 2010;24:161–168. 2. neumatikos IA, Dragoumanis CK, Demosthenes EB. Ventilator associated pneumonia or endotracheal associated pneumonia. Anesthesiology. 2009;110:673–680. 3. alencia M, Torres A. Ventilator associated pneumonia. Curr Opin Crit Care. 2009;15:30–35. 4. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia: Official statement of ATS and IDSA 2004. Am J Respir Crit Care Med. 2005;171:388–416.

5. oenig SM, Truwit JD. Ventilator-associated pneumonia: Diagnosis, treatment, and prevention. Clin Microbiol Rev. 2006;19(4):637–657.

ADDITIONAL READING

• Craven D, Chroneou A. Nosocomial pneumonia. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. 3717–3738. • O’Keefe-McCarthy S, Santiago C, Lau G. Ventilator associated pneumonia bundled stratgies: An evidence based practice. Worldviews on Evid Based Nurs. 2008;5(4):193–204.

See Also (Topic, Algorithm, Electronic Media Element) • Intubation and extubation criteria • Atelectasis

CODES ICD9 997.31 Ventilator associated pneumonia ICD10 J95.851 Ventilator associated pneumonia

CLINICAL PEARLS

• VAP is a nosocomial pneumonia that develops after more than 48 hours of mechanical ventilation. • Currently there are no consensus guidelines for the diagnosis of VAP. The CPIS score combines clinical, radiographical, laboratory, and microbiologic information to aid in diagnosis and treatment and is commonly used. • Preventive measures should be a cornerstone of therapy.

VENTRICLES Ali Salehi, MD

BASICS DESCRIPTION

Ventricles generate ejection pressure to maintain perfusion in the pulmonary and systemic vasculature, house part of the cardiac conduction system (His Bundle, bundle branches, and Purkinje fibers), and produce cardiac natriuretic peptides (in a lesser role than atria). PHYSIOLOGY PRINCIPLES

• Ventricular contraction and relaxation consists of 4 stages: – Isovolumetric contraction: Marks the beginning of ventricular systole. Ventricular volume is constant and equal to end diastolic volume. This stage ends with all 4 valves closed. – Ventricular ejection: Contraction continues and eventually exceed pulmonary pressures on the right and aortic pressures on the left, with resultant opening of the pulmonary valve (PV) and aortic valve (AV), respectively. Blood is ejected into the pulmonary and systemic vasculature and the ventricular volume decreases. It should be noted that electromechanical relaxation (diastole) begins at the end of this phase, while blood is being ejected. – Isovolumetric relaxation: Begins after the pulmonary and aortic valves close (chamber pressures drop below pulmonary artery and aortic pressures). The ventricular volume remains unchanged. – Ventricular filling: Ventricular pressures continue to drop until they fall below atrial pressures, resulting in the opening of the TV and MV. The ventricles passively fill due to the pressure gradient between the atria and the ventricles until the pressures equilibrate. Then the atria contract and lead to further, active venticular filling. Ventricular volume is maximal at the end of diastole (∼140 cc). • Right ventricle (RV): Contraction is described as sequential with the trabeculated portion (RV inflow) contracting first, followed by the infundibulum (longest duration 25–50 ms), and finally the smooth muscle portion. RV contraction consists of 3 mechanisms: Inward contraction of the free wall, longitudinal fiber contraction with apical descent of the tricuspid annulus, and traction on the free wall at the points of attachment due to LV contraction (1). Longitudinal shortening is more prominent than radial shortening. Additionally, the larger surface-to-volume ratio compared to the LV, result in a smaller inward motion being needed to eject the same stroke volume (SV). • Left ventricle (LV): Receives oxygenated blood and pumps it into the systemic circulation. LV contraction consists of: Longitudinal fiber contraction and apical descent of the MV, inward motion of the LV walls, and apical (counter-clockwise) and basilar (clockwise) twist. • Comparing RV to LV systole and contraction: – Duration of isovolumetric phases: LV > RV – Onset of contraction: LV before RV

– Onset of ejection: RV before LV (lower afterload) – Duration of ejection: RV longer than LV – Peak ejection velocity: LV > RV – Peak ejection: RV occurs after LV • Comparing RV to LV diastole and filling: – Duration of filling: RV begins before and finishes after the LV – Isovolumetric relaxation time: LV > RV – RV filling velocities are smaller than the LV. – Respiratory variations in the ventricular filling are more prominent in the RV than in the LV. – Compliance: RV > LV – Pericardium has a greater constraint on the RV than the LV. • Ventricular interdependence describes the effect in changes of the size, shape, and compliance of one ventricle or the other. – Systolic interdependence is mediated through the IVS. – Diastolic interdependence. RV volume or pressure overload can result in RV dilation that pushes the IVS toward the LV. This results in an increase in left ventricular end diastolic pressure along with a decrease in LV elastance, left ventricular end diastolic volume, and cardiac output (2). ANATOMY

• RV: Most anteriorly located cardiac chamber; lies underneath the sternum (thus, it is prone to cardiac contusions from trauma). Forms most of the anterior surface and the entire inferior border of the heart. It is connected to the right atrium through the TV and pumps deoxygenated blood to the pulmonary vasculature through the PV. – Base: Comprised of the TV, the largest of the cardiac valves (area ∼4–6 cm2 and 3 leaflets). These leaflets are attached to 3 papillary muscles (anterior, posterior, and septal) via chordae tendineae. – Apex: Located at the midpoint between the middle third and lower third of the IVS. – IVS: Composed of a membranous and muscular segment separating the ventricles. The membranous portion is smaller and superiorly located. The muscular part of the IVS is thicker than the RV free wall (2–3 times) due to higher intraventricular pressures generated in the LV during systole. The IVS moves toward the LV in systole and toward the RV in diastole. – Free wall: About 6–7 mm thick and is covered with muscle bundles (trabeculae carneae).

FIGURE 1. Right ventricle anatomy. (Jiang L. Right Ventricle. In: Weyman AE, ed. Principle and Practice of Echocardiography. Baltimore, MD: Lippincott Williams & Wilkins; 1994: 901–921.

– RV inflow tract (RVIT) and RVOT have separate embryologic origins, and are separated by a circular muscle bundle. The RVIT is located inferoposteriorly and has trabeculated walls. The RVOT is located anterosuperiorly and has smooth walls. • LV: Forms the apex of the heart, the entire left (pulmonic) surface and border, and most of the diaphragmatic surface of the heart. It is connected to the left atrium (LA) through the MV and pumps the oxygenated blood into the systemic circulation through the AV. – Base: Comprised of the MV and has 2 leaflets (anterior and posterior). They are attached to 2 papillary muscles (anterolateral and posteromedial) through chordae tendineae. Chordae tendineae prevent the leaflets from everting into the atrium during systole. – Apex: Located at the level of the left 5th intercostal space at the midaxillary line. – 6 walls: Anterior, anterolateral (lateral), anteroseptal, inferior, inferolateral (posterior), inferoseptal (septal). Each wall is divided into 3 segments (basal, middle, and apical). This classification aids with identifying the coronary artery that may be responsible for a new wall motion abnormality. – IVS: The anterior part of the septum is trabeculated while the posterior portion is smooth. The latter portion is called the inlet septum due to proximity to the atrioventricular valves (TV, MV). The membranous portion of the IVS is located between the inlet portion and the trabeculated part of the septum.

FIGURE 2. Left ventricle internal anatomy. (From: Multimedia Library, Children’s Hospital of Boston 2011, Robert Geggel, M.D. editor. Diagrams by Emily Flynn McIntosh.

DISEASE/PATHOPHYSIOLOGY

• Ventricular septal defects (VSD): Associated with a left-to-right shunt leading to RV volume overload, RV dilatation, pulmonary hypertension and eventually RV failure. When RV pressures surpass LV pressures, there is a reversal of flow and a right-to-left shunt, which may cause systemic hypoxemia and cyanosis (Eisenmenger’s syndrome). There are 4 types: – Muscular VSD: Results from defects in the trabeculated portion of the septum. They are completely rimmed by muscle, and can occur anywhere in the muscular septum. – Membranous VSD: True defects of the membranous septum are surrounded by fibrous tissue without extension into the adjacent muscular septum. If they extend in the muscular septum they are called perimembranous or infracristal. – Inlet VSD: Defects in the posterior smooth walled (inlet) part of the IVS. There is no muscular rim between the defect and the AV annulus; they can be part of the AV canal defect. – Supracristal (also known as subarterial, subpulmonary, or conal) VSD: Defects in the infundibular septum divide the RVOT from the LVOT (3). • Premature ventricular contractions (PVCs): Arise from ectopic foci in the ventricular myocardium and have a slow propagation velocity. This results in a bizarre-shaped widened QRS complex on the ECG. They are unable to excite the bundle of His, so there is no retrograde conduction to the atria or SA node. The next “P” wave will be buried in the PVC and unable to excite the ventricles, but the second “P” wave after the PVC will be conducted and produce ventricular depolarization. Thus, there is always a pause after the PVC. They can be unifocal or multifocal. PVC frequency <7/min is of no clinical consequence; however, multifocal PVCs or runs of PVCs can be precursors for ventricular tachycardia and fibrillation. • Ventricular tachycardia: Series of rapid regular ventricular depolarizations. They interfere with adequate ventricular filling and cause hemodynamic instability. • Ventricular fibrillation: Ventricular myocardium contracts in a totally irregular and

ineffective manner due to rapid discharges from multiple ventricular ectopic foci or circus movement. Ventricles cannot fill adequately, which leads to a significant drop in cardiac output and blood pressure. A fibrillating ventricle appears like a “sack of worms.”

PERIOPERATIVE RELEVANCE

• Auscultation of a harsh holosystolic murmur in a child during preoperative evaluation should alert the practitioner to a possible VSD and encourage further work-up. • Patients with impaired ventricular function due to any cause should be carefully evaluated preoperatively to see whether they are adequately medically managed and compensated. – Signs and symptoms that point to uncompensated heart failure include shortness of breath, cold clammy extremities, low BP, tachycardia, crackles on pulmonary auscultation, elevated JVP, lower extremity edema, and decreased exercise tolerance. – The anaesthetist should consider postponing the procedure if possible, so that the patient can be adequately optimized. • In patients with reduced ventricular function, invasive monitoring (arterial line, central line, pulmonary artery catheter) should be considered. Placement of an arterial line is usually indicated with significant reduction in ventricular function (EF < 25%) or procedures with risk of significant blood loss, fluid shifts, or sudden changes in BP. Pulmonary artery catheters are usually indicated in patients with uncompensated heart failure or unstable angina undergoing urgent/emergent surgery to direct fluid resuscitation, patients with heart failure undergoing high-risk procedures, or patients with RV failure and pulmonary hypertension. • If ventricular tachycardia or fibrillation occurs perioperatively, the practitioner should initiate appropriate ACLS protocols and medical treatment and look out to correct any underlying cause. • Patients with hypertrophic cardiomyopathy or low ejection fraction will have a defibrillator device implanted to prevent ventricular arrhythmias and sudden death. These devices need to be interrogated preoperatively and the treatment options turned off because electrocautery used by the surgeons can cause interference and be sensed by the device as an abnormal rhythm. This can elicit a shock, which can harm both the patient and the surgical team.

REFERENCES

1. Haddad F, Hunt SA, Rosenthal DN, et al. RV function in cardiovascular disease, Part I: Anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation. 2008;117:1436–1448. 2. Haddad F, Hunt SA, Rosenthal DN, et al. RV function in cardiovascular disease, Part II: Pathophysiology, clinical importance, and management of right ventricle failure. Circulation. 2008;117:1717–1731. 3. Minette MS, Sahn DJ. Ventricular septal defects. Circulation. 2006;114:2190–2197.

ADDITIONAL READING

• Ganong WF. “Origin of the Heartbeat and the Electrical Activity of the Heart", Review of

Medical Physiology 20th ed., United States, McGraw-Hill; 2001:528–544. • Moore KL, Dalley AF, Agur AMR. “Thorax”, Clinically Oriented Anatomy 6th ed, Philadelphia PA, Lippincott Williams & Wilkins; 2010:135–160. See Also (Topic, Algorithm, Electronic Media Element)

• Atria • Coronary arteries • Ventricular fibrillation • Premature ventricular contractions • Ventricular tachycardia

CLINICAL PEARLS

• The ventricles eject blood to the pulmonary and systemic circulation, and are prone to ischemia, congenital defects, and rhythm disturbances.

VENTRICULAR FIBRILLATION Jonathan K. Ho, MD Aman Mahajan, MD, PhD

BASICS DESCRIPTION

• Ventricular fibrillation (VF) describes disorganized and continuous electrical activity of the ventricular myocardium due to various inciting causes, resulting in cessation of cardiac output. • VF is often preceded by ventricular tachycardia.

EPIDEMIOLOGY Prevalence

• Sudden cardiac death carries an incidence of 0.1–0.2% per year and causes 400,000 deaths per year in US, the majority of which are due to VT/VF. • Unknown intraoperative incidence, although considered rare.

Mortality

• Cessation of cardiac output due to VF is fatal unless a perfusing rhythm is re-established. • Mortality is dependent on timely and appropriate intervention to treat the arrhythmia and underlying causes. • Operating room: 75% survival rate and 57% survival rate to discharge. • Non-OR interventional procedural areas: 64% survival rate and 41% survival rate to discharge. ETIOLOGY/RISK FACTORS

• Procedure-based risk: – Intrathoracic/cardiac procedures – ICD testing, interventional cardiac catheterization procedures • Patient comorbidities: – Cardiomyopathy – Ischemic heart disease – Brugada syndrome • Metabolic derangements: – Electrolyte disorders – Acid–base disorders – Hypothermia – Hypoxia • Myocardial ischemia or acute coronary syndromes • Pathologic events: – Hypovolemia

– Pulmonary embolus – Tension pneumothorax – Cardiac tamponade • Iatrogenic causes: – Microshock/macroshock – R on T phenomenon (asynchronous pacing, lithotripsy) – Drug toxicity

PHYSIOLOGY/PATHOPHYSIOLOGY

• VF is defined by multiple re-entrant waves of electrical activity that conduct erratically through the myocardium. Dispersion of refractoriness and heterogeneity of conduction properties within the myocardium contribute to the perpetuation of disordered electrical and mechanical activity. • Mechanical activity is completely unsyncrhonized and uncoordinated (described as “quivering") and is insufficient to pump blood out of the heart. Cardiac arrest ensues and without emergency intervention, can be fatal within minutes.

PREVENTATIVE MEASURES

• VF is a common end point for many critical pathologic processes. Avoid inciting events (ischemia, cardiac manipulation, micro/macroshock, electrolyte/acid–base derangements, surges in autonomic stimulation). • Anticipate the potential need for defibrillation in vulnerable patient populations. Consider pre-emptive placement of defibrillator pads on the patient, or having them in the room. • Patients predisposed to VT/VF may have implanted cardioverter defibrillators (ICDs). Device interrogation may yield pertinent information regarding arrhythmia burden.

PREOPERATIVE ASSESSMENT • Physical examination – In conscious patients, palpitations may precede VF, with rapid loss of consciousness. – Absent pulses. – Absent heart sounds. – Jugular venous distention (from the cardiac pump “backing up”). • Monitors – EKG with characteristic disorganization of electrical activity. – Loss of ETCO2; cessation of blood flow to the alveoli, with continued ventilation results in dead space ventilation. The PaCO2 continues to increase, as it cannot be exhaled.

– Loss of plethysmography waveform/arterial line pulsatility. – Hypotension. – Disorganized contraction on TEE. • Labs – Serum electrolyte panel (including calcium and magnesium). – Arterial blood gas analysis to detect hypoxia.

DIFFERENTIAL DIAGNOSIS

• Pulseless VT (Polymorphic VT/torsades de Pointes) • Pulseless electrical activity • Ventricular asystole • Monitoring errors, EKG artifact

TREATMENT • In the operating room, VF is often witnessed, the airway is secured, IV access is present, and skilled personnel is available. • ACLS protocol with CPR and early/immediate defibrillation: – Monophasic 360 J – Biphasic 120–200 J – Pediatric 2–4 J/kg, up to 10 J/kg • Vasopressor (epinephrine/vasopressin) therapy is considered after the first shock and CPR with the goal of improving myocardial perfusion via increased aortic root pressure. – Epinephrine 1 mg IV q3–5 minutes – Vasopressin 40 units IV may be substituted for the first and second dose of epinephrine • Consider amiodarone 300 mg IV bolus; a second dose of 150 mg may be given if no response. • Lidocaine 1–1.5 mg/kg up to 3 mg/kg may be considered if amiodarone is not available. • The underlying cause must be diagnosed and treated. VF may be refractory to defibrillation if causes of VF are not addressed (e.g., ischemia).

FOLLOW-UP • If hemodynamic stability and a stable cardiac rhythm are recovered promptly, continuing with the surgical procedure may be considered depending on the inciting event and feasibility of interrupting or delaying surgical procedure. • Must assess end-organ impact if a prolonged period of hypoperfusion occurred. • If diagnosis or treatment of the etiology is an ongoing process, a therapeutic strategy must be developed and care should be continued in an intensive care setting. – Consider therapeutic hypothermia if neurologic insult is suspected. – Identify and treat acute ischemia if present. – Provide respiratory support. – Provide hemodynamic support as needed to maintain end-organ perfusion. – Assess prognosis and recovery potential.

REFERENCES

1. hyre JM, Ramachandran SK, Kheterpal S, et al. Delayed time to defibrillation after intraoperative and periprocedural cardiac arrest. Anesthesiology. 2010;113(4):782–793. 2. Mahajan A, Hoftman N. To beat or not to beat: is timing the only question? Survival after delayed defibrillation. Anesthesiology. 2010;113(4): 765–766. 3. Peberdy MA, Callaway CW, Neumar RW, et al. Part IX: post–cardiac arrest care: 2010

American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122:S768–S786.

ADDITIONAL READING

• Cardiac electrophysiology: From cell to bedside. Douglas P. Zipes, José Jalife. Saunders/Elsevier, 2009.

See Also (Topic, Algorithm, Electronic Media Element) • Advanced cardiac life support anesthetic management • Pulseless electrical activity • Circulatory arrest • Electrical safety in the OR

CODES ICD9 427.41 Ventricular fibrillation ICD10 I49.01 Ventricular fibrillation

CLINICAL PEARLS

• Early defibrillation may positively impact outcome. • Be prepared to defibrillate in vulnerable patients/procedures. • Inciting event and underlying causes must be considered and addressed.

VENTRICULAR HYPERTROPHY Brian L. Marasigan, MD

BASICS DESCRIPTION

• Ventricular hypertrophy describes the increased growth and enlargement of ventricular muscle. It may occur in both the right (RVH) and left ventricles (LVH), but is most common in the left. • Ventricular hypertrophy occurs when work increases for the muscle and it grows to compensate. Any condition that increases resistance to forward flow or otherwise increases wall stress may lead to the muscular hypertrophy. EPIDEMIOLOGY Prevalence

Minimal data exists for general left ventricular hypertrophy (LVH) incidence and prevalence over the last 5 years Prevalence

• Prevalence in adult males 16% and females 19% • At age >70 years, prevalence is 33% in men and 49% in females.

Morbidity

LVH is an independent risk factor for: • Stroke • Congestive heart failure (CHF) • Coronary artery disease • Sudden cardiac death Mortality

Acute myocardial infarction and sudden cardiac death are direct effects of LVH physiology. Survival depends on resolving the underlying condition prior to irreversible muscular damage. ETIOLOGY/RISK FACTORS

• Age • Hypertension • Obesity • Pulmonary (RVH) or aortic disease (LVH) • Hypertrophic cardiomyopathy • Myocardial infarction • Extensive athleticism or pregnancy

• Fabry’s disease

PHYSIOLOGY/PATHOPHYSIOLOGY

• Ventricular hypertrophy • In the absence of genetic cardiomyopathy, hypertrophy is a physiologic response of increased work or stress on the ventricle, leading to the creation of new sarcomeres and muscle mass. • Pathologic responses (neurohormonal effects, muscle injury, idiopathic cardiomyopathy, volume overload, hypoxia) may also cause muscle mass to increase, with collagen deposition (4)[A]. • Concentric hypertrophy • A physiologic response to increased work or stress on the ventricle, leading to the creation of new sarcomeres and muscle mass. The increase in mass/width results in impaired lusitropy (relaxation) and compliance (potentially smaller diastolic ventricular cavity). • Primarily due to pressure overload conditions, such as chronic hypertension, aortic stenosis, or other chronic outflow tract obstructions; healthy athletes may even develop LVH in response to chronic exercise. • Increases in muscle mass result in impaired lusitropy (relaxation) and compliance (potentially smaller diastolic ventricular cavity). • Diastolic dysfunction may occur due to left ventricular stiffening. In addition, functional concentric hypertrophy may remodel to eccentric hypertrophy after a myocardial infarction (1). • Eccentric hypertrophy • Often caused by volume overload conditions with resultant dilation of the chamber as well as early dysfunction and decompensation. • Increases in muscle mass result from collagen deposition. • Oxygen supply and demand. • Decreased supply: It becomes more difficult to adequately perfuse the muscle due to increased thickness and increased left ventricular end diastolic pressure (LVEDP) • Increased demand: Myocardial depolarization, contraction, and relaxation are energydependent processes. The increase in muscle mass results in increased consumption. • Left and right ventricles • LVH; more common in adults. • Right ventricular hypertrophy (RVH): Right-sided heart lesions such as pulmonary stenosis, right ventricular outflow tract (RVOT) obstruction, or shunts are more often found in children and require early repair. In adults, it can result from pulmonary hypertension or pulmonary stenosis. Because the right ventricle is designed for low pressure and has a low muscular mass, it is more likely to decompensate relative to the left ventricle, especially in acute situations. • Dysfunction and decompensation: Ventricular hypertrophy occurs over years and without treatment of the underlying cause, it can lead to diastolic (impaired relaxation and decreased compliance) and systolic (impaired contractility) dysfunction. Decompensation can manifest as ischemia, infarction, arrhythmias, and CHF. ANESTHETIC GOALS/GUIDING PRINCIPLES

Maintenance of cardiac output, coronary perfusion, and prevention of cardiac decompensation are the primary goals. • Control hypertension (afterload), while maintaining adequate perfusion pressures. • Maintain an optimal fluid balance; patients often have a decreased preload, but can easily develop volume overload with fluid administration. • Decrease myocardial oxygen demand: Inotropy, chronotropy (consider beta-blockers). • Maintain cardiac output with inotropes to provide forward flow, if necessary. Although it increases oxygen consumption, maintaining perfusion is critical. • Manage valvular dysfunction, if present.

PREOPERATIVE ASSESSMENT SYMPTOMS

• LVH may be asymptomatic for decades • Fatigue • Dyspnea on exertion • Angina • Symptoms related to the underlying cause of hypertrophy (i.e., valvular disease)

History

• HTN in the morning may be a strong predictor of concentric hypertrophy (5)[B]. • Family history or previous diagnosis of cardiomyopathy, HTN, cardiac valvular disease, congenital valve disease. • Commonly diagnosed after symptomatic exercising or during workup for diastolic or systolic CHF or angina. • Previous cardiomegaly on chest x-ray.

Signs/Physical Exam • Syncope • CHF

MEDICATIONS

• Afterload reduction: Calcium channel blockers, angiotensin-converting enzyme inhibitors, beta-blockers, nitrovasodilators • Heart failure treatments including digoxin, ACEI/ARB, and diuretics

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Basic metabolic profile: Electrolyte and kidney function • Chest x-ray: Cardiopulmonary status • Electrocardiogram: Electrical criteria (see later) • Echocardiogram: Diagnosis and classification of disease severity and ventricular systolic and diastolic function. Wall thickness at end diastole

CONCOMITANT ORGAN DYSFUNCTION

• Hypertension • Pulmonary hypertension, congestion, and pleural effusion • Valvular disease

CIRCUMSTANCES TO DELAY/CONDITIONS • Decompensated CHF • Recent myocardial infarction or stroke • Uncontrolled HTN

CLASSIFICATIONS

• LV wall thickness for concentric LVH • Normal: 0.8–1.2 cm • Mild: 1.2–1.5 cm • Moderate: 1.5–2.0 cm • Severe: 2.0 cm or greater • EKG determinants of LVH • Sokolow + Lyon: S wave V1 + R wave V5, or V6 >35 mm • Framingham criteria: Any of the following: – R wave AVL >11 mm – R wave V4–6 >25 mm – S wave V1–3 >25 mm – S wave V1 or V2 + R wave V5 or V6 >35 mm – R wave Lead I + S wave Lead III >25 mm

TREATMENT PREOPERATIVE PREPARATION Premedications

• Benzodiazepines to prevent anxiety and blunt the sympathetic tone • Antihypertensive medication, if indicated

Special Concerns for Informed Consent

Risk for cardiac issues: Ischemia, infarction, arrhythmias INTRAOPERATIVE CARE Choice of Anesthesia

Dependent upon surgical procedure, surgeon preference, and comfort of the anaesthetist. • Sedation: Minimal hemodynamic changes • General: Hemodynamic swings may be seen with induction (hypotension), laryngoscopy and intubation (hypertension), maintenance (hypotension), and emergence (hypertension) • Neuraxial: Sympatholysis may be profound in chronic hypertensives due to increased vascular tone and intravascular hypovolemia Monitors

• Standard ASA monitors • 5-lead EKG to detect arrhythmias, ischemia; the V5 lead is useful in detecting abnormalities in the left ventricle’s apex • Arterial line may be considered for beat-to-beat BP monitoring • Central venous line may be considered to monitor fluid and medication infusion • Pulmonary artery catheter may be considered if there is a high risk for decompensation, and allows monitoring of both the right and left ventricular functions • Transesophageal echocardiography may be considered for the diagnosis and management of perioperative events

Induction/Airway Management

• Smooth controlled induction to maintain vital signs within normal limits • Minimize the duration of laryngoscopy

Maintenance

• Balanced technique with volatile or intravenous anesthetic. • Hypotension may result from intravascular volume depletion and/or decreased sympathetic tone. Consider administering low-dose phenylephrine, gentle fluid boluses, or nitrous oxide (allows decreases of volatile agent while maintaining depth of anesthesia) as appropriate; upon emergence, hypotension often resolves. • Analgesia: Regional anesthesia or narcotics may aid with hemodynamic stability

Extubation/Emergence

Hypertension is common; be prepared to treat.

FOLLOW-UP BED ACUITY

Depends on the type of surgery and patient comorbidities MEDICATIONS/LAB STUDIES/CONSULTS

• Postoperative 12-lead EKG, if ischemia or cardiac event suspected intraoperatively • Cardiac enzymes, if appropriate • Postoperative echocardiogram, if unstable • Standard postoperative fluid and electrolyte management and related laboratory studies

COMPLICATIONS

• Perioperative arrhythmia • Mental status changes and stroke • Myocardial Infarction

REFERENCES

1. Desai RV, et al. Natural history of concentric left ventricular geometry in communitydwelling older adults without heart failure during seven years of follow-up. Am J Cardiol.

2011;107(2):321–324. 2. Schirmer H, Lunde P, Rasmussen K. Prevalence of left ventricular hypertrophy in the general population; the Tromso study. Eur Heart J. 1999;20(6):429–438.

3. Cuspidi C, et al. Prevalence and severity of echocardiographic left ventricular hypertrophy in hypertensive patients in clinical practice. Blood Press. 2010;20(1):3–9. 4. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling—concepts and clinical implications: A consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35(3):569–582.

5. Matsui Y, et al. Morning hypertension assessed by home monitoring is a strong predictor of concentric left ventricular hypertrophy in patients with untreated hypertension. J Clin Hypertens. 2010;12(10):776–783.

ADDITIONAL READING

• Mann DL, Bristow MR. Mechanisms and models in heart failure: The biomechanical model and beyond. Circulation. 2005;111(21):2837–2849. See Also (Topic, Algorithm, Electronic Media Element)

• Perioperative hypertension • Afterload • Lusitropy • Left ventricular end diastolic pressure (LVEDP) • Aortic stenosis • Hypertrophic cardiomyopathy

CODES ICD9 429.3 Cardiomegaly ICD10 I51.7 Cardiomegaly

CLINICAL PEARLS

• Ventricular hypertrophy may occur in both the left and right ventricles, and is classified as either concentric or eccentric. • Concentric hypertrophy is a functional increase in muscle mass and may be seen in healthy athletes or pressure overload conditions, such as hypertension and aortic stenosis. • Eccentric hypertrophy is a pathologic increase in muscle mass and collagen, and is seen with volume overload and other pathologic conditions such as myocardial infarction. • LVH may be diagnosed and classified by echocardiography or EKG. CT, MRI or chest x-ray may be used as well. • Perioperative care centers around the type of surgery as well as type and severity of

hypertrophy.

VENTRICULAR SEPTAL DEFECT Alain A. Salvacion, MD James D. Boone, MD

BASICS DESCRIPTION

A ventricular septal defect (VSD) is an opening or defect in the ventricular septum. EPIDEMIOLOGY Prevalence

• Live births: 1.56–53.2 per 1,000; detection has increased due to better imaging and screening • Median incidence of 2,829 per 1 million live births

Prevalence

• Most common form of congenital heart disease (CHD) in childhood. • Second most common form of CHD in adults (after bicuspid aortic valve). Accounts for 10– 15% of defects. • Of all VSDs noted at age 1 month, 80% close spontaneously.

Morbidity

• Depends on size, pulmonary vascular resistance (PVR), and degree of left-to-right shunting • Increases with multiple VSDs, pulmonary hypertension, and complex associated anomalies • VSD repair is associated with an overall risk less than 5% • Excellent outcomes can be expected when the VSD is repaired before age 2

Mortality

• On the basis of studies of the natural history of VSD, 27% of patients die by age 20 years, 53% by age 40 years, and 69% by age 60 years. • Overall 25-year survival rate for all patients managed with medical or surgical therapy is 87%. ETIOLOGY/RISK FACTORS

• Etiology – In vitro, can result from a deficiency of growth or a failure of alignment or fusion of component parts of the endocardial cushion/ventricular septum. – Myocardial infarction. – Iatrogenic causes are usually related to procedures that require passage of wires and foreign objects within the heart (e.g., electrophysiology ablations). • Congenital risk factors – Maternal marijuana and alcohol use

– Maternal and paternal cocaine use – The recurrence risk in offspring of paternal VSD is 2%. – The recurrence risk in offspring of maternal VSD is 6–10% – The risk is increased in certain chromosomal disorders such as Down’s syndrome.

PHYSIOLOGY/PATHOPHYSIOLOGY

• The physiologic consequences are determined by the size of the defect, degree of left-toright shunting, and PVR. • Small VSDs allow only a modest increase in pulmonary blood flow, resulting in minimal functional disturbance. • Moderate and large defects with low PVR are associated with significant left-to-right shunting. With time, the volume overloaded pulmonary vasculature can develop pulmonary hypertension with resultant right heart failure. • Over time, irreversible increases in PVR may occur, leading to reversal of flow and Eisenmenger’s syndrome (right-to-left shunting, cyanosis, pulmonary vascular disease).

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Assess the severity of disease and left-to-right shunt as well as the presence of pulmonary hypertension, heart failure, and Eisenmenger’s syndrome. • Avoid acute and persistent increases in systemic vascular resistance (SVR) or decreases in PVR that may accentuate left-to-right shunting. • Focus on preserving ventricular function, particularly, the right ventricle. • Large increases in PVR can reverse the shunt to right-to-left, which may impair oxygenation. • Both inhalational and IV agents are well-tolerated. IV agents have a slower onset (shunting results in a recirculating effect within the heart and lungs, as opposed to being ejected into the arterial system). Volatile agents, particularly soluble agents, have a faster onset of action (less agent is absorbed from the alveoli by the pulmonary capillaries; hence alveolar concentrations remain increased and correlate to brain concentrations).

PREOPERATIVE ASSESSMENT SYMPTOMS

• Assess for symptoms of heart failure such as dyspnea, orthopnea, and paroxysmal nocturnal dyspnea • Assess for symptoms of arrhythmias such as palpitations • Poor weight gain and failure to thrive in infants

History

• Age at diagnosis • Exercise tolerance • Other accompanying congenital heart defects and anomalies

Signs/Physical Exam

• Signs of RV failure such as peripheral edema, distended jugular veins, hepatojugular reflux, ascites, hepatomegaly

• Signs of LV failure such as pulmonary edema • Signs of arrhythmias such as tachycardia or an irregularly irregular pulse • A pansystolic murmur is best heard at the left sternal border

TREATMENT HISTORY

• Previous procedures for the treatment of VSD or other congenital heart defects

MEDICATIONS

• Heart failure medications • Pulmonary hypertension medications • Antiarrhythmic medications • Anticoagulation

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• ECG may show right atrial deviation, right ventricular hypertrophy, or left ventricular hypertrophy. • CXR may be normal initially but may show cardiomegaly and pulmonary edema if in heart failure. • Echocardiogram is diagnostic. • Cardiac MRI can also be diagnostic. • Right heart catheterization to assess PVR and PA pressures, especially if there is a large or longstanding defect. • Left heart catheterization in older patients and those at risk for CAD. • Calculation of Qp:Qs shunt; >1.5–2 is an indication for surgery.

CONCOMITANT ORGAN DYSFUNCTION

• Pulmonary edema in LV failure • Predisposed to pulmonary infections • Liver dysfunction due to hepatic congestion in RV failure • Renal dysfunction due to prerenal state in heart failure

CIRCUMSTANCES TO DELAY/CONDITIONS

• Improve volume status if the patient is fluid overloaded • Optimize pulmonary hypertension, if reversible • Treat pulmonary infection • Control arrhythmias

CLASSIFICATIONS

• Perimembranous (70%) • Muscular (20%) • Infundibular (5%) • Inlet (5%)

TREATMENT PREOPERATIVE PREPARATION Premedications

• In patients with Eisenmenger’s syndrome, administration should be done very cautiously (if at all), as hypercarbia and hypoxia can increase the PVR and worsen right-to-left shunting (impairs oxygenation). • Consider antibiotic prophylaxis.

Special Concerns for Informed Consent Parental consent if a minor INTRAOPERATIVE CARE Choice of Anesthesia

• Dependent on the procedure as well as the surgeon’s, patient’s, and anaesthetist’s preference. • Patients with smaller VSDs will tolerate all forms of anesthesia. • In patients with Eisenmenger’s syndrome, LV and/or RV impairment, consider local anesthesia and peripheral nerve blocks if the procedure permits. Monitors

• Dependent on the extent of the procedure. • Small VSDs may not need invasive monitoring. • Patients with large and longstanding defects may benefit from an arterial line for continuous BP monitoring and a central line for administering and monitoring vasopressor support. • Consider a pulmonary artery catheter and/or transesophageal echocardiography for cases involving large volume shifts. Induction/Airway Management

• Patients with small VSDs may tolerate any type of induction. • Avoid anesthetics that may further depress systolic function in patients with poor myocardial reserve. • Avoid hypoxia, hypercarbia, and acidosis in patients with pulmonary hypertension (especially those with Eisenmenger’s syndrome). Maintenance

• Avoid persistent increases in SVR (worsens left-to-right shunting) and decreases in PVR during the procedure. • Patients with RV and LV impairment are at increased risk for fluid overload; monitor carefully • Intravenous medications may have a decreased onset (decreased amount enters the systemic circulation; left ventricle shunts into the right ventricle). Volatile agents, on the other hand, may have a quickened onset (increased alveolar, and hence, brain concentrations).

Extubation/Emergence

• Extubate when appropriate • Patients with Eisenmenger’s syndrome poorly tolerate hypercarbia and hypoxia.

FOLLOW-UP BED ACUITY

• Monitor fluid status closely • Monitor for arrhythmias • ICU care if the patient underwent a high-risk procedure, or has a large VSD, poor myocardial function, or Eisenmenger’s syndrome

MEDICATIONS/LAB STUDIES/CONSULTS

Providers with experience in CHD may be helpful, especially in patients with complex lesions. COMPLICATIONS

• Monitor for fluid overload and worsening RV and/or LV function in patients with poor myocardial reserve. • Patients are at risk for arrhythmias.

REFERENCES

1. annesson M, et al.Anesthesia for noncardiac surgery in adults with congenital heart disease. Anesthesiology. 2009;111:432–440. 2. Minette M, Sahn D. Ventricular septal defects. Circulation. 2006;114:2190–2197. 3. Ammash NM, Warnes CA. Ventricular septal defects in adults. Ann Intern Med. 2001;135(9):812–824.

ADDITIONAL READING

• www.americanheart.org • www.mayoclinic.com/health/ventricular-septal-defect

See Also (Topic, Algorithm, Electronic Media Element) • Patent foramen ovale • Pulmonary hypertension

CODES ICD9 745.4 Ventricular septal defect ICD10 Q21.0 Ventricular septal defect

CLINICAL PEARLS

• It is important to assess the severity of the disease, the extent and direction of shunting, and the degree of myocardial impairment in order to plan for an appropriate anesthetic technique. • Intravenous medications have a decreased onset due to left-to-right shunting; volatile agents (in particular, highly soluble agents) have an increased onset. The FA/FI rises more quickly.

VENTRICULAR TACHYCARDIA Rob C. Tanzola, MD, FRCPC Brian Milne, MD, MSc, FRCPC

BASICS DESCRIPTION

• Ventricular tachycardia (VT) originates from a focus below the AV node. It is characterized by a heart rate >100 bpm and a wide QRS complex (>120 milliseconds). • Classification is based on QRS morphology, duration, and/or hemodynamic consequences. – QRS morphology: Monomorphic or polymorphic. – Duration: Sustained (episode >30 seconds) or non-sustained (episode <30 seconds). – Hemodynamic consequences: Stable or unstable. EPIDEMIOLOGY Prevalence

• Ventricular arrhythmias (including PVCs) under general anesthesia: 6.3% (severe 0.6%). • Perioperative VT or >30 PVCs/hr in patients at high risk for coronary artery disease: 44% (15.7% incidence intraoperatively). Morbidity

• VT is usually an indicator of an underlying cardiac derangement. • Sustained VT may result in low cardiac output and/or degenerate into ventricular fibrillation. Mortality

Dependent on the cause and duration of the VT and the patient’s physiologic reserve. ETIOLOGY/RISK FACTORS

• Acquired cardiac disease: Cardiomyopathy, myocardial scar, myocardial ischemia, myocarditis. • Congenital heart disease: Aortic coarctation, Ebstein’s anomaly, tetralogy of Fallot, Brugada syndrome. • Prolonged QT: Congenital and/or drug-induced (e.g., droperidol, methadone, sotalol, procainamide, domperidone, amiodarone). • CNS disease: Subarachnoid hemorrhage, spinal cord injury. • Respiratory failure: Hypoxia, hypercarbia • Electrolyte abnormalities: Hypokalemia, hyperkalemia, hypomagnesemia, acidosis. • Excess sympathetic stimulation: Sympathomimetic drugs, endogenous catecholamines (e.g., perioperative stress, pheochromocytoma). • Thermal instability: Hypothermia (<28°C), malignant hyperthermia. • Drug overdose (e.g., digitalis, cocaine, tricyclic antidepressants, local anesthetics).

• Iatrogenic: Microshock/macroshock, cardiac irritation (e.g., pulmonary artery catheter).

PHYSIOLOGY/PATHOPHYSIOLOGY

• VT mechanisms include re-entry, enhanced automaticity, and triggered activity. • Reentry mechanism requires more than one potential activation pathway, unidirectional block in one pathway, and slow conduction through the area of block to allow reentry into the circuit. – Usual causes of monomorphic VT – Example: Myocardial infarction scar • Enhanced automaticity entails a rapid rate of discharge from typically latent pacemaker cells in the ventricle. – Spontaneous phase 4 impulse formation of the cardiac action potential, which is usually involved in producing an escape rhythm, becomes the cardiac pacemaker. – Examples: Enhanced automaticity from catecholamines in damaged tissue (acute ischemia, prior infarction), enhanced sympathetic stimulation. • Triggered activity occurs secondary to after-depolarizations (oscillations in the myocyte membrane voltage are produced by a preceding action potential). – Early after-depolarizations occur in the plateau phase of the cardiac action potential and can cause PVC’s or polymorphic VT. – Delayed after-depolarizations occur due to increases in intracellular calcium. This is associated with beta agonists and/or digoxin.

PREVENTATIVE MEASURES

• Avoid sympathetic stimulation: Adequate depth of anesthesia, pain control. • Prophylactic antiarrhythmic agents have no demonstrated survival benefit and may be arrhythmogenic. • Implantable cardioverter-defibrillators (ICDs): Decreases the incidence of sudden death in patients with LV dysfunction. • Long-QT syndrome therapy: beta-blockers, avoidance of QT-prolongation drugs, ICD, avoidance of hypokalemia or hypomagnesium, left cervicothoracic sympathetic ganglionectomy, stellate ganglion block. • Anesthesia with low arrhythmogenic potential – Induction/maintenance: Propofol, sevoflurane, nitrous oxide. – Avoidance of sympathetic stimulants: Halothane, ketamine, sympathomimetics.

PREOPERATIVE ASSESSMENT • Definitive diagnosis of VT may be difficult and time-consuming. In a hemodynamically unstable patient, emphasis should be placed on prompt treatment rather than diagnosis. • History of MI, angina, or heart failure increases the likelihood of VT. • ECG findings suggestive of VT – Wide QRS complex (>120 msec) – Atrioventricular dissociation: Visualization of P waves in or between QRS complexes. Only present <50% of the time – Fusion beats: Convergence of an action potential through both the normal pathway and

the ectopic focus producing a QRS complex of mixed morphology. – Capture beat: Atrial impulse arriving at the AV node when the ventricular myocardium is available for depolarization; results in a QRS complex of normal morphology. – Precordial concordance: QRS complexes with the same polarity in V1–V6 have a 90% specificity for VT. • Arterial line readings may demonstrate changes in BP that reflect variable atrial contribution to filling. • Central and pulmonary catheter waveforms may demonstrate cannon “A” waves that reflect atrial contraction against a closed AV valve.

DIFFERENTIAL DIAGNOSIS

Other sources of wide-complex tachycardias:

• Supraventricular tachycardia (SVT) with abnormal interventricular conduction accounts for 15% of wide-complex tachycardias • Pre-excited tachycardias (e.g., Wolff–Parkinson–White syndrome) • Ventricular paced rhythms

TREATMENT • Pulseless VT – CPR – Defibrillation (200 J biphasic, 360 J monophasic). DO NOT delay shock to determine if monomorphic or polymorphic VT. – Identify and treat the underlying cause • Stable monomorphic VT – Procainamide: 20–50 mg/min IV until the arrhythmia is suppressed, hypotension occurs, or the QRS widens by 50%. The maximum cumulative dose is 17 mg/kg or 100 mg every 5 minutes. Avoid if a prolonged QT interval or significant LV dysfunction. – Amiodarone: 150 mg IV over 10 minutes (repeat if necessary), followed by 1 mg/min infusion for 6 hours. – Sotalol: 1.5 mg/kg IV over 5 minutes. Avoid if prolonged QT interval or significant LV dysfunction. – Lidocaine (second-line therapy): Less effective in terminating VT than procainamide, sotalol, or amiodarone. – Avoid verapamil and diltiazem in stable VT, associated with profound hypotension. – Elective synchronized cardioversion: 100 J (mono or biphasic), increase in stepwise fashion if no response. – Anti-tachycardia pacing: Internal pacemaker or external pacing (rarely). • Polymorphic VT – Defibrillate immediately as patients have a tendency to degenerate into VF. – Assess the QT duration following defibrillation. In patients with a normal QT interval, ischemia is the most common cause of polymorphic VT. Treat with amiodarone and/or beta-blocker. • Torsades de Pointes

– Defibrillation (200 J biphasic, 360 J monophasic). – Avoid QT-prolonging agents – Avoid Class IA and III anti-arrhythmic agents (K+ blocking properties) – Correct electrolytes. Magnesium sulfate 1–2 grams IV over 15 minutes. Administer potassium if patient is hypokalemia (maintain a high-normal level of 4.5–5 mmol/L) – Increase heart rate: Atropine, isoproteronol, electrical pacing. Increasing the heart rate >90 bp, can suppress early after-depolarizations and shorten the QTc. • Familial long QT syndrome – Avoid sympathetic stimulation – Consider beta-blockade – Thoracic epidural, left stellate ganglion block, left surgical cardiac sympathetic denervation.

Pediatric Considerations

• Causes of ventricular arrhythmias in children include congenital heart disease, cardiomyopathies, inflammatory myocardial disease, and electrical myopathies. • A significant number of structurally normal hearts have PVCs and VT that are generally well tolerated. Benign patterns have a normal sinus rhythm repolarization, normal ventricular function, and no family history of sudden death. • Cardioversion at 0.5–2 J/kg, if unstable.

Pregnancy Considerations

• Elevated catecholamines during labor and delivery may predispose to VT. • New onset VT should prompt consideration of peripartum cardiomyopathy. • Cardioversion is indicated in unstable patients and those who fail medical treatment.

FOLLOW-UP • Invasive monitoring and intensive care setting postoperatively. • 12-lead EKG: Assess QT duration and indicators of myocardial ischemia. • Labs: Electrolytes, Ca2+, Mg2+, ABG, cardiac enzymes, toxicology screen. • Echocardiogram: Assess for structural heart disease and evidence of ischemia. • Cardiology/electrophysiology consultation – Anti-arrhythmic therapy – Electrophysiology study, ablation, or ICD – Treatment/follow-up of coronary disease • MRI is imaging test of choice for ARVC. • Genetic screening for familial disorders

CLOSED CLAIMS DATA

• 74 closed claims with VT during anesthesia – 70% during GA, 19% regional, and 8% MAC – Causes: Unexplained (25%), wrong drug or dose (12%), intravascular injection/absorption of local anesthetic (10%), airway management (9%), electrolyte imbalance or inappropriate fluid management (7%).

REFERENCES

1. eumar RW, Otto CW, Link MS, et al. Part VIII: Adult advanced cardiovascular life support: 2010 AHA Guidelines for CPR and Emergency Cardiovascular Care. Circulation. 2010;122: S729–S767. 2. Pellegrini CN, Scheinman MM. Clinical management of ventricular tachycardia. Curr Probl Cardiol. 2010;35:453–504.

3. Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the ACC/AHA Task Force and the European Society of Cardiology Committee for Practice Guidelines. Circulation. 2006;114:e385–e484. See Also (Topic, Algorithm, Electronic Media Element) • Tachycardia • Wolffe–Parkinson–White syndrome • QT prolongation

CODES ICD9 427.1 Paroxysmal ventricular tachycardia ICD10 I47.2 Ventricular tachycardia

CLINICAL PEARLS

• Common etiologies of VT: Hypoxemia, hypomagnesemia, hypokalemia/hyperkalemia, myocardial ischemia, pulmonary embolism, and excess sympathetic stimulation. • Unstable VT should be immediately defbrillated (200 J biphasic, 360 J monophasic). • Stable VT can be treated with antiarrhythmic drugs or synchronized cardioversion (100 J). • In patients with a history of VT, avoid anesthetic drugs that have been associated with it: succinylcholine (hyperkalemia); droperidol (QT prolongation and Torsades de Pointes); naloxone (sympathetic stimulation in opioid-dependent patient).

VENTRICULO–PERITONEAL SHUNT Jose M. Soliz, MD Sessunu M. Zemo, MD

BASICS DESCRIPTION General

• Ventriculo-peritoneal (VP) shunt is a surgical procedure that is performed to treat hydrocephalus; it diverts CSF from the ventricles to the peritoneal cavity. • CSF is produced by the choroid plexus in the lateral, third, and fourth ventricles. To maintain homeostasis and turnover, it drains in the following manner: – Fourth ventricle, into the – Lateral foramina of Luschka and medial foramen of Magendie, into the – Subarachnoid space, into the – Arachnoid villi, into the – Dural sinus, and into the – Venous drainage • Normal CSF production is 0.20–0.35 mL/min. Total volume of CSF in an adult is 125–150 mL. • Hydrocephalus is a congenital or acquired pathologic condition marked by an increased amount of CSF that may or may not be associated with increased pressure (1). It is classified into 3 causes: – Excessive CSF production – Obstruction of CSF pathways (non-communicating) – Decreased CSF absorption (communicating) proximal to the foramina of Lushka and Magendie at the outlet of the fourth ventricle • During surgical placement of VP shunts, an incision is made over the anticipated area of ventricular cannulation, and a Burr hole is made into the cranium that allows placement of a thin, flexible ventricular catheter. An additional incision is made over the anticipated site of peritoneal insertion and is dissected down to the peritoneum. A valve is attached to the ventricular catheter (outside the cranium) and a thin, long distal catheter is subsequently attached (this mechanism allows the valve to open and drain fluid when excessive pressure develops). The distal catheter is tunneled SC from the scalp down the neck and chest to the peritoneal incision with the help of a shunt passer. • An additional incision behind the ear can be made to aid with tunneling of the distal catheter (and can be the location where the valve sits). • Alternative cerebral shunts include: – Ventriculo-atrial shunt (VA shunt) – Ventriculo-pleural shunt (VPL shunt) – Lumbar-peritoneal shunt (LP shunt)

Position

• Supine with the head turned; or slightly lateral position • Scalp is shaved over the frontal or parietal region • Prep the patient from the head to the peritoneum • Table turned 90 or 180°

Incision

• Made over the posterior parietal region to access the occipital horn or over the coronal suture to access the frontal horn. • An incision posterior to the ear may also be performed. • Peritoneal incision with dissection down to the peritoneum. Some centers employ laparoscopic distal catheter placement in the peritoneal cavity; however, this may adversely increase intracranial pressures (ICPs).

Approximate Time 1.5 hours

EBL Expected Minimal

Hospital Stay 2–3 days

Special Equipment for Surgery

• Peritoneal and ventricular catheters • Valve • Shunt passer

EPIDEMIOLOGY Prevalence

• Congenital hydrocephalus occurs in 1–2/1,000 live births. • Acquired hydrocephalus varies due to many specific causes.

Prevalence

Present in all age groups, from the newborn to the elderly. Morbidity

Surgical complications include: • Infection <1% • Intracranial bleeding <1% • Hardware failure Mortality

Surgical mortality is <1%

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Performance of a thorough preoperative neurologic examination and documentation of any neurologic symptoms or deficits. • Maneuvers to decrease or avoid increased ICP. • Incision and tunneling of the catheter are stimulating; anticipate and prevent wide swings in BP and heart rate. • Prevention of postoperative nausea and vomiting. • Extubate when the patient is able to protect his or her airway.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Headache • Blurred vision • Nausea/vomiting

History

• Determine the underlying cause. • Review the patient’s medication list. Electrolyte imbalance and metabolic acidosis can occur with medications commonly used to treat hydrocephalus.

Signs/Physical Exam

• Increased head circumference • Increased ICP: Nausea, vomiting, altered mental status, bradycardia and hypertension (Cushing’s response), bradycardia without hypertension, change in ventilation pattern, irritability, papilledema (2).

MEDICATIONS

• May be used to delay surgical treatment or treat symptoms of hydrocephalus. Not effective as long-term treatment. – Decrease choroid plexus secretion: Acetazolamide, furosemide, spironolactone, and corticosteroids – Increase CSF absorption: Isosorbide • If seizures occur, patients may require antiepileptic medications. Serum levels should be checked preoperatively.

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• CT or MRI will identify the site of malfunction. • Lumbar puncture and ICP monitoring can aid in the diagnosis.

CONCOMITANT ORGAN DYSFUNCTION Gastric hypotonia

TREATMENT PREOPERATIVE PREPARATION Premedications

• Avoid sedation; hypoventilation and/or hypoxia can exacerbate intracranial hypertension and can potentially lead to tonsillar herniation. • H2 blockers to decrease the acidity of gastric contents may be considered Special Concerns for Informed Consent

• Patients who have severe neurologic impairment may not be able to provide consent. • There is a possibility of shunt failure and the need for shunt revision or replacement.

Antibiotics/Common Organisms

• Antibiotics are aimed at the prevention of meningitis and surgical site infection. The most commonly administered are cefazolin, vancomycin, or gentamicin. • Common organisms include Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), S. epidermidis, and Gram-negative organisms.

INTRAOPERATIVE CARE Choice of Anesthesia General anesthesia Monitors

• Standard ASA monitors • One large bore IV: 18–20 gauge

Induction/Airway Management

• Standard IV induction with propofol or etomidate allows for rapid onset with concomitant decreases in ICP. Drops in the mean arterial BP can impair cerebral perfusion pressure (CPP = MAP – ICP) and should be avoided, anticipated, and treated as appropriate. • Full stomach: Consider a modified rapid sequence induction (if appropriate) to reduce the risk of aspiration. Intubation prior to an adequate depth of anesthetic or attainment of muscle relaxation can dangerously elevate the ICP (from Valsalva, coughing, bucking). Although succinylcholine can transiently increase the ICP, it is typically mild; the benefits of its fast onset often outweigh the risk. Maintenance

• Maintenance can be achieved with a combination of volatile or intravenous agent, nitrous oxide, narcotic, and/or muscle relaxation medications. Volatile agents uncouple cerebral autoregulation and have the potential for increasing the ICP. • Ventilation: If the ICP is increased, hyperventilation may be appropriate; otherwise, normocarbia should be maintained. • Hemodynamics: Maintain normotension. Hypertension and tachycardia may be seen during incision and tunneling.

• Fluids: Replete any fluids lost due to emesis or dehydration. Otherwise, administer as needed. • Temperature: The exposure of a large body surface area makes the patient prone to hypothermia. Employ appropriate warming techniques early.

Extubation/Emergence

• Standard extubation criteria apply: An awake, fully responding patient is desired. • Adequate reversal of neuromuscular blockade. • Suction gastric contents before extubation to prevent aspiration. • Hypothermic patients should be rewarmed prior to extubation.

FOLLOW-UP BED ACUITY

• Intermediate monitoring unit or standard room. • Intensive care unit may be appropriate depending upon the patient’s preoperative status and comorbidities.

ANALGESIA

• Pain is typically mild • Local anesthetic infiltration at incision sites (cranial and abdominal) may decrease discomfort and the need for IV or PO analgesia. • Acetaminophen, NSAIDS, or tramadol as needed. Minimize narcotic usage when feasible. Maintain the ability to obtain a neurologic examination.

COMPLICATIONS

• VP shunts are prone to malfunction and shunt revision is common. It is estimated that within the first 12 months, 30–50% of shunts will fail (3). • Infection • Overdraining or underdraining of CSF • Hematoma or hygroma • Seizures

PROGNOSIS

Depends on the cause of hydrocephalus, associated disorders, and success of treatment. Pediatric Considerations

• Because an infant’s fontanelles are not closed, they can compensate for increases in CSF. Presenting signs/symptoms include a rapidly enlarging head, tense fontanelles, vomiting, irritability, seizures, dilated scalp veins, and “setting sun”/“sundowing” sign (eyes deviate downward when eyelids are retracted).

REFERENCES

1. Reddy GK, Bollam P, Caldito, et al. Ventriculoperitoneal shunt complications in

hydrocephalus patients with intracranial tumors: An analysis of risk factors. J Neurooncol. 2010;103(2):333–342. 2. Livingston JH, McCullagh HG, Kooner G, et al. Bradycardia without associated hypertension: A common sign of ventriculo-peritoneal shunt malfunction. Childs Nerv Syst. 2010;27(5):729–733. 3. Wan KR, Toy JA, Wolfe R, et al. Factors affecting the accuracy of ventricular catheter placement. J Clin Neurosci. 2011;18(4):485–488. See Also (Topic, Algorithm, Electronic Media Element) • Intracranial hypertension • Hypothermia

CODES ICD9 • 331.4 Obstructive hydrocephalus • V45.2 Presence of cerebrospinal fluid drainage device ICD10 • G91.9 Hydrocephalus, unspecified • Z98.2 Presence of cerebrospinal fluid drainage device

CLINICAL PEARLS

• Increased ICP increases the risk of perioperative vomiting, leading to aspiration. • ICP can be lowered intraoperatively with hyperventilation and IV induction agents. • The most stimulating parts of the procedure are during incision and tunneling of the shunt catheter.

VERTEBROPLASTY AND KYPHOPLASTY Elizabeth A.M. Frost, MD

BASICS DESCRIPTION General

• Minimally invasive vertebral augmentation techniques are used for the palliative treatment of vertebral compression fractures from osteoporosis or malignancies in patients not responding to conservative treatment or who continue to have severe pain. • A filler material, or bone cement, is injected percutaneously into the collapsed or weakened vertebral body in order to stabilize and strengthen the fractured bone. Pain relief is likely due to the mechanical support. – Vertebroplasty: The filler is injected directly into the bone – Kyphoplasty: The filler is injected after the establishment of a cavity by inflation of a balloon tamp. The balloon tamp provides a method to control where the delivered cement goes and may also serve to restore some of the compressed height of the vertebra. • The procedures are often performed in interventional radiology suites where the requisite special imaging equipment is readily available; it can also be performed in the operating room. • Following local anesthetic injection to the area, biopsy needles (10–13 gauge), usually bilaterally, are introduced to the collapsed or fractured vertebra under fluoroscopic guidance (transpedicular approach). • In vertebroplasty, once the needles are in the correct position, the filler is slowly injected into the vertebral body. It diffuses through the intertrabecular marrow space and creates an internal case that stabilizes the bone. One or more vertebral levels may be treated according to the pathology. • In kyphoplasty, once the needles are in the correct position, small balloons may then be introduced and inflated in the vertebral body to create a void within the cancellous bone and compact it against the sides of the vertebrae. The balloons are withdrawn and acrylic cement is injected through the biopsy needles where it hardens quickly. • Once the needles are removed, small bandages are applied to the puncture sites. • Advantages over conservative management or surgery: – Avoids prolonged hospitalization – Immediate pain relief and discontinuation of narcotics – Increased height and improvement of vital capacity and FEV1 • Disadvantages: – Leak of filler material causes transient local pain – Hypotension, hypoxemia, pulmonary embolism (all very rare) – Controversial efficacy; recent studies have suggested no improvement over placebo.

Position

Complete prone, neutral Incision

Small puncture wounds on both sides of vertebrae Approximate Time 45 minutes

EBL Expected Minimal

Hospital Stay

Ambulatory or overnight depending on the patient’s comorbidities Special Equipment for Surgery

• Imaging equipment, usually in interventional radiology suite • Filler material

Incidence

• Osteoporosis in the US: 10 million people (1) • Low bone mass in the US: 34 million people • Bone fractures in patients diagnosed with osteoporosis have a 1:2 incidence in women and 1:4 incidence in men • Vertebral compression fractures: >700,000/year

Prevalence

Increases with age, female gender Morbidity

• Cost of osteoporosis: $14 billion in direct national expenditure. • From the procedure: – Radicular pain – Hypotension, hypoxemia, and pulmonary embolism are rare events that can result from filler material emboli

Mortality

Single case report of perforation of a myocardial ventricle ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patient population with significant comorbidities • Positioning difficulties secondary to pain. In addition, the prone position precludes easy access to the airway and complicates airway management • Minimally invasive, however narcosis and sedation are essential. The patient must lie still while being able to communicate with and follow commands from the proceduralist (e.g., breath holding, neurologic examination)

PREOPERATIVE ASSESSMENT SYMPTOMS

• Severe pain • Motor weakness, poor sensation from neurologic deficits

History

• Chronic pain, multiple therapies • Careful assessment of comorbidities • Malignant fractures are often metastasized from the primary tumor. Determine primary site, and chemotherapeutic agents

Signs/Physical Exam

Sensory or motor deficits MEDICATIONS

• Narcotic patches, anxiolytics, antidepressants • Cardiac medications • Respiratory inhalers • Herbal preparations (often Chinese community) • Chemotherapeutic agents for malignant fractures (evaluate for adriamycin, doxorubicin)

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• PT/PTT, INR • CBC • Chemistries (Na, K, Cr) • Consider CXR, EKG, as appropriate

CONCOMITANT ORGAN DYSFUNCTION • Coronary artery disease • Restrictive lung disease • Urinary tract infection • Depression • Metastatic cancer

TREATMENT PREOPERATIVE PREPARATION Premedications

• Supplemental oxygen • Anxiolysis, analgesics, and/or sedation may be needed to achieve prone positioning – Anxiolytics (short-acting like midazolam)

– Analgesia (fentanyl, alfentanil, ketamine, sufentanil, dexmedetomidine, remifentanil) – Sedation (propofol, benzodiazepines, analgesics)

Special Concerns for Informed Consent

• Clear communication during the preoperative period about the procedure and positioning • Reasonable sedation goals (communication is required and poor airway access preclude heavy sedation) • Discomfort typically only with local anesthetic and filler injection; pain or discomfort should be communicated to the health team • Changes in foot or leg sensation should be communicated promptly • Breath holding may be required • Rare and transient decrease in oxygenation may occur and is related to filler injection

INTRAOPERATIVE CARE Choice of Anesthesia

• Monitored anesthesia care (MAC)/deep sedation is the preferred method. – Awake neurologic monitoring – Minimizes hemodynamic swings associated with a general anesthesia – Avoids airway instrumentation – Reduces the potential for postoperative cognitive dysfunction that may be seen with some elderly patients • General anesthesia with endotracheal tube may be warranted in certain circumstances – Pain precludes positioning – Dementia or other disease may preclude lying still – Difficult airway that would make airway management difficult if the patient becomes hypoxic or obstructs

Monitors

• Standard ASA monitors, including end tidal CO2 monitoring

• Long lines or extensions may be needed as the table is moved

Induction/Airway Management

• Monitored anesthesia care – Supplemental oxygen via NC, FM – Have a supraglottic airway available – Sedation, anxiolysis, analgesia are titrated gently to avoid oversedation, loss of ability to communicate. – Implementation of medications should be titrated based upon onset time, duration of action, comorbidities, airway, age, and side effects. Choices include midazolam, fentanyl, propofol, dexmedetomidine, remifentanil, and ketamine. CAREFUL titration is recommended to avoid respiratory depression, particularly in the prone position. • General anesthesia – Standard induction with ETT placement – Induction agent based upon cardiac status (propofol versus etomidate)

– Muscle relaxation can optimize intubating conditions and prone positioning (coughing and bucking). Intubating doses of nondepolarizing agents may not be reversible by the end of the procedure. Consider lower doses or succinylcholine, if appropriate.

Maintenance

• Monitored anesthesia care – Titrate sedation and analgesia to comfort, ability to communicate – Treat hypertension (consider labetalol, hydralazine, metoprolol) – Treat hypotension (phenylephrine, ephedrine) – Be aware of cumulative respiratory and cardiac effects of medications and duration of action – Constant assessment and evaluation of breathing • General anesthesia – Volatile or IV maintenance – Appropriate and judicious analgesic administration, as patients should awaken relatively pain free from the procedure

Extubation/Emergence

• Monitored anesthesia care – Typically able to get off of the table, relatively pain free • General anesthesia – Per routine, in supine position, adequate NMBD recovery/reversal (if utilized), responds to commands

POSTOPERATIVE CARE BED ACUITY

• Patients need to lie flat on their back for a short period of time to allow for cement hardening. • 23-hour or overnight observation to assess for neurologic changes. • Discharge within 2–3 hours may be appropriate in some patients, if neurologically intact.

ANALGESIA

NSAIDs are sufficient to treat pain from puncture wounds COMPLICATIONS

• Puncture site hematoma • New fractures of neighboring vertebrae

REFERENCES

1. National Institutes of Health Osteoporosis and Related Bone Diseases – National Resource Center (www.osteo.org) 2. Anselmetti GC, Corrao G, Monica PD, et al. Pain relief following percutaneous vertebroplasty: Results of a series of 283 consecutive patients treated in a single institution.

Cardiovasc Intervent Radiol. 2007;30(3):441–447 3. Bolster MB. Consternation and questions about two vertebroplasty trials. Cleve Clin J Med. 2010;77(1):12–16. Cosar M, Sasani M, Oktenoglu T, et al. The major complications of transpedicular vertebroplasty. J Neurosurg Spine. 2009;11(5):607–613.

4. Hulme PA, Krebs J, Ferguson SJ, et al. Vertebroplasty and kyphoplasty: A systematic review of 69 clinical studies. Spine. 2006;31(17):1983–2001. 5. Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med. 2009;361(6): 569–579 (Trial registration: Current Controlled Trials ISRCTN81871888). 6. Luginbuhl M. Percutaneous vertebroplasty, kyphoplasty and lordoplasty: Implications for the anesthesiologist. Curr Opin Anaesthesiology. 2008;219(4):504–513.

7. Orr RD. Vertebroplasty, cognitive dissonance, and evidence-based medicine: What do we do when the “evidence” says we are wrong? Cleve Clin J Med. 2010;77(1):8–11. See Also (Topic, Algorithm, Electronic Media Element) • Radiation safety • Postoperative cognitive dysfunction

CLINICAL PEARLS

• Although minimally invasive, often performed in elderly patients with multiple comorbidities, including cardiac disease, respiratory compromise related to kyphosis and repeated aspiration, urinary tract infection, metastasis, multiple drugs including narcotic dependency, poor nutritional status, and limited mobility; increasing need to involve anaesthetists. • MAC sedation to allow for neurologic assessment; however, general anesthetic may be induced under certain circumstances. • Prone position may be difficult and precludes good access to the airway. • Studies questioning long-term benefits are under review. • Better patient selection may be indicated.

VIDEO-ASSISTED THORACOSCOPIC SURGERY (VATS) Jagtar Singh Heir, DO

BASICS DESCRIPTION General

• Video-assisted thoracoscopic surgery (VATS) is a minimally invasive technique first described by Dr. Jacobeus in 1910. However, it did not gain widespread use until the early 1990s (1). • Although it was initially used to treat tuberculosis-induced pleural effusions, it has much broader applications today: – Diagnostic uses: Assessing pleural disease (TB); staging of lung, esophageal, mediastinal, and other cancers; diagnosing parenchymal disease; and pericardial biopsy (2). – Therapeutic uses: Decortications; empyemectomy; lung resection (wedge, lobectomy, bilobectomy, pneumonectomy); pericardial window; esophageal surgery (vagotomy, antireflux procedures, minimally invasive esophagectomy); sympathectomy; and coronary artery disease and valve procedures (2). • Carbon dioxide is utilized for insufflation and lung collapse. A thoracoscope is inserted into the chest and allowed for images to be transmitted to a video monitor. Additional surgical instruments can be inserted depending upon the procedure (biopsy, resection, bovie, etc.) in a similar manner as laparoscopic instruments. At the end of the procedure, the lung is reinflated, a chest tube may be placed through one of the incisions, and the remaining incisions are closed. • Potential benefits of VATS compared to thoracotomies (however, randomized controlled studies to support these benefits are lacking) (3): – Minimally invasive – Cosmetically more pleasing (smaller incisions, muscle sparing) – Decreased pain – Shorter hospital stays – Improved pulmonary mechanics – Decreased cost

Position

Lateral decubitus, often with a bean bag and axillary roll. Incision

Ranges from 2–5 small incisions used to introduce thoracoscopic instruments Approximate Time 1.5–3 hours

EBL Expected

Usually minimal; however, as large vascular structures are nearby, the risk of significant bleeding is a possibility Hospital Stay 2–3 days

Special Equipment for Surgery

• Thoracoscope • Video monitors • Double lumen tube (DLT) or bronchial blocker (BB) • Capability to convert to open thoracotomy • Postoperative chest tube

EPIDEMIOLOGY Prevalence

Depending on the institution, between 60–80% of all thoracic cases performed involve some component of a VATS procedure Morbidity

• Potential for major vascular injury (pulmonary artery or vein, SVC, aorta) • Atrial fibrillation: 10% (4) • Air leak: 7.2% • Pneumonia: 2% • Respiratory failure: 2% • Arrhythmias, particularly atrial fibrillation • Conversion to open thoracotomy

Mortality

<1% for elective procedures

ANESTHETIC GOALS/GUIDING PRINCIPLES

• The physiology and management of one lung ventilation (OLV) needs to be understood. • Preparations for blood loss and conversion to an open technique should be made. • Careful positioning and padding may decrease the incidence of nerve injuries. • Patients with pulmonary disease may decompensate with splinting and guarding from pain. Adequate postoperative analgesia may decrease the occurrence.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Often asymptomatic as lesions can be found incidentally during investigation • Respiratory complaints may include productive or non-productive cough, dyspnea, wheezing, hemoptysis

History

• Underlying respiratory or intrathoracic pathology • Careful assessment of other comorbid disease processes (e.g., coronary artery disease [CAD], COPD) Signs/Physical Exam

• Wheezing, rales, rhonchi, tachypnea • Frequent upper respiratory infections

MEDICATIONS

• Bronchodilators • Chemotherapeutic agents • Medications related to comorbidites

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Electrolytes, creatinine, CBC, coagulation profile (PT/PTT/INR). • Pulmonary function tests (PFTs) and arterial blood gases (ABGs) may be useful for prognostication. • CT scan if obstruction, large lesions, or vascular involvement is suspected. • CXR combined with CT can help discern any potential obstruction which may make DLT placement difficult. CONCOMITANT ORGAN DYSFUNCTION

Often determined by the age group. Older patients with thoracic disease processes can have an increased incidence of CAD, peripheral vascular disease (PVD), and chronic obstructive pulmonary disease (COPD).

TREATMENT PREOPERATIVE PREPARATION Premedications

• Antiarrhythmics: Perioperative beta-blockade, calcium channel blockers, amiodarone, flecainamide, and fish oils may be instituted and continued perioperatively. • Bronchodilators (puffs or nebulizers), steroids • Deep venous thrombosis (DVT) prophylaxis • Type and screen or cross

Special Concerns for Informed Consent

• Blood consent for possible need for transfusion • Potential to convert to open • Potential for postoperative intubation • Consent for possible epidural catheter, or intercostal block placement

INTRAOPERATIVE CARE

Choice of Anesthesia

• General anesthesia with a DLT is utilized for the vast majority of procedures. • Simple diagnostic or drainage procedures may be performed with a combination of local anesthesia and sedation; however, spontaneous ventilation can make the procedure more challenging. • Epidural placement at a T7–T8 level or higher may be considered.

Monitors

• Standard ASA monitors • Arterial line is useful for close hemodynamic monitoring and drawing of frequent labs (HCT, ABGs); may not be necessary for short procedures or healthier patients (ASA I, II) • 2 large-bore IVs for rapid resuscitation in cases where conversion to open thoracotomy becomes necessary • Foley catheter should be considered

Induction/Airway Management

• Slow, controlled induction is advised as many patients have CAD, PVD, HTN • Lung isolation and separation is best accomplished with a DLT, but BBs may be needed in patients where this is not feasible. Although BBs may be easier to place in patients with difficult airways, they may be easily dislodged (particularly in right sided placement) and do not allow for intermittent suctioning or continuous positive airway pressure (CPAP) to the operative lung.

Maintenance

• The controversy regarding total intravenous anesthesia (TIVA) versus inhalation agents still persists in thoracic surgery; a recent meta-analysis failed to demonstrate one technique being superior to the other. Proponents of TIVA suggest that it avoids inhibition of hypoxic pulmonary vasoconstriction seen with inhalational agents. Conversely, advocates of inhalation anesthesia assert that it is associated with a lower release of inflammatory mediators and provides bronchodilation. • Ventilation – Settings: FIO2 of 1.0. Lower tidal volumes (TVs) of 5–7 cc/kg are utilized to decrease

ventilator-induced alveolar damage. – Hypoxia: Although CPAP can improve oxygenation to the “shunted” non-dependent lung, it can simultaneously hinder visualization and impair the feasibility of the procedure. Alternatively, positive end expiratory pressure (PEEP) may be applied to the dependent lung. Intermittent inflation of the non-dependent lung is less likely to hinder the progress of VATS procedures. • Epidural infusion: The decision to begin the infusion intraoperatively, after blood loss is complete, at closure, or with smaller local anesthesia concentration or higher opioid dosing intraoperatively, is practitioner dependent. One should weigh the risks of a combined sympatholysis with blood loss against the benefit of decreased anesthetic requirements • Volume restriction is a point of contention; the literature suggests that other factors such as advanced age, smoking history, large amount of lung tissue resected, history of congestive

heart failure, and/or TVs exceeding 10–12 cc/kg are more important factors. The concept of goal-directed therapy with non-invasive cardiac output monitors or TEE (high risk patients) is advocated by some.

Extubation/Emergence

• Standard criteria • In patients with pulmonary disease, an ABG may be drawn to aid in assessing extubation parameters. • Avoidance of coughing and bucking are desired to decrease the incidence of injury to new anastomosis of the trachea or pulmonary vessels.

FOLLOW-UP BED ACUITY

• Telemetry for patients who have had more complex procedures. • Regular recovery may be considered for patients with smaller or diagnostic procedures.

ANALGESIA

• Pain is typically mild; however, dyspnea and visceral discomfort make pain scores difficult to predict. • Preoperative placement of an epidural catheter (T8 level or higher) may be considered for patients with chronic pain issues or where conversion to an open procedure is likely. Alternatively, some institutions now utilize paravertebral blocks in lieu of epidurals; however, they bear the risk of vascular injury and pneumothorax. • Intercostal nerve blocks • Elastomeric pumps with continuous infusion of local anesthetics may be administered along the incision site. • NSAIDs such as ketorolac (30 mg) or PO opioids. Systemic narcotics might impair respiratory function (morbidly obese, OSA) • About one-third of the patients complain of referred ipsilateral shoulder pain; this can be treated with a suprascapular block with variable success if opioids are not a desirable option.

COMPLICATIONS

• The most feared complication is a tension pneumothorax in procedures where a chest tube may not have been placed. It can manifest in a variety of ways but can lead to tracheal shift and subsequent sudden cardiac collapse. • Air leak from damaged lung parenchyma • Hemorrhage from injury of intrathoracic vascular structures • Empyema, lung infection or infection at the site of port entry, pneumonia • Pulmonary edema, postoperative fever, leukocytosis, and small pleural effusions are relatively common. • Deep venous thrombosis (DVT) may occur in patients with morbid obesity, cancer, peripheral vascular disease, or longer procedures.

REFERENCES

1. Braimbridge MV. The history of thoracoscopic surgery. Ann Thorac Surg. 1993;56:610– 614. 2. Fischer GW, Cohen E. An update on anesthesia for thoracoscopic surgery. Curr Opin Anaesthesiol. 2010;3:7–11. 3. Flores RM, Alam N. Video-assisted thoracic surgery lobectomy (VATS), open thoracotomy and the robot for lung cancer. Ann Thorac Surg. 2008;85:S710–S715. Shaw JP, Dembitzer FR, Wisnivesky JO, et al. Video assisted thoracoscopic lobectomy: State of the art and future directions. Ann Thorac Surg. 2008;85:S705–S709.

4. Dreyfuss D, Soler P, Basset G, et al. High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis. 1988;137:1159–1164.

ADDITIONAL READING

• Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC, eds. Clinical Anesthesia. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2009. • Yao F-SF, Fontes ML, Malhortra V, eds. Anesthesiology Problem-Oriented Patient Management. 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2008.

See Also (Topic, Algorithm, Electronic Media Element) • One lung ventilation • Double lumen tubes • Pulmonary function tests (PFTs) • Perioperative beta-blockers • Pneumothorax • Pneumonectomy

CLINICAL PEARLS

• As surgeons will have to convert to an open procedure if large bleeding occurs, it is imperative to be prepared to vigorously resuscitate as this conversion can be challenging, given the impaired visual field and time needed to convert to open.

VOCAL CORD PALSY Angela Truong, MD Dam-Thuy Truong, MD

BASICS DESCRIPTION

• Vocal cord (VC) palsy refers to the absence of VC motion due to injury to the vagus nerve or its branches, the superior laryngeal nerve (SLN) and/or the recurrent laryngeal nerve (RLN). – The SLN innervates the cricothyroid muscle (VC tensor) – The RLN innervates the posterior cricoarytenoid muscle (VC abductor) and the rest of the intrinsic laryngeal muscles (VC adductors). • Immobility of the VC refers to the absence of VC motion from any cause including disorders of the laryngeal joints. • Palsy of the VC may compromise important physiologic functions of the larynx: Breathing, swallowing, airway protection, and speech. Injury may: – Be unilateral or bilateral – Involve partial or complete transection – Result as a complication after head and neck surgery and has a potential for airway obstruction after extubation. – Require anesthesia care for phonosurgery EPIDEMIOLOGY Prevalence

• Post-thyroidectomy 1.6–2.9%; left VC affected twice as often as the right VC • Post-cardiovascular surgery: 2.3%

Prevalence

Increased with age >50 yrs, hypertension, diabetes mellitus (DM), and prolonged intubation Morbidity

• Dyspnea, dysphagia, ineffective cough, and recurrent aspiration • Psychological distress and professional issues related to voice impairment

Mortality

Rare, but can result from: • Complete airway obstruction secondary to unsuspected partial bilateral recurrent nerve injury after extubation from head and neck surgery • Pulmonary aspiration and recurrent aspiration pneumonias in bilateral VC palsy ETIOLOGY/RISK FACTORS • Surgical trauma (44%)

– Bilateral VC injury can occur after surgery involving thyroid, parathyroids, esophagus, and trachea – Left VC palsy can occur after mediastinal or cardiac surgery since the left RLN loops under the aortic arch before traversing up to the neck • Cancers (17%) include laryngeal tumors, chondromas/chondrosarcomas, and squamous cell carcinomas • Traumatic intubation or prolonged intubation (15%) leading to posterior subglottic stenosis • Neurologic causes (12%) include DM, amyotrophic lateral sclerosis, and myasthenia gravis • Inflammatory causes include Wegener’s granulomatosis, amyloidosis, sarcoidosis, polychondritis, and gastroesophageal reflux diseases (GERD) • Idiopathic (12%)

PHYSIOLOGY/PATHOPHYSIOLOGY

• VC palsy can result from injury at three levels: – Centrally at the main trunks of the vagus nerve – Peripherally at its branches – Directly at the VCs themselves • Injury to SLN: The cricothyroid muscle is unable to tense the VCs, giving a weak and husky voice. • Injury to RLN: Abductors are more vulnerable to injury. Therefore, partial nerve damage may result in a selective abductor paralysis while a complete transection paralyzes both adductors and abductors. – Unilateral complete transection: Results in a paralyzed VC that lies midway between adduction and abduction, just lateral to the midline. Speech is not seriously affected because the normal VC compensates by moving toward the paralyzed VC – Unilateral partial transection: If the abductors are more severely paralyzed than the adductors, the affected VC lies in the midline, adducted position and can decreases the glottic opening – Bilateral complete transection: VCs are positioned midway between abduction and adduction. It is often erroneously believed to cause both vocal cords to meet at the midline and create complete airway obstruction: however, complete transection paralyzes both abductors and adductors. Breathing is still possible, however, the glottic opening is smaller than normal. This scenario is akin to administering succinylcholine; there is still an opening that allows for intubation – Bilateral partial transection: If the abductors are paralyzed but the adductors are spared, the adductors will bring the vocal cords to the midline and cause complete airway obstruction

PREVENTATIVE MEASURES

• Avoid traumatic and prolonged intubation • Prevent RLN injuries during surgery, especially during thyroidectomy by identifying and preserving the nerve at its point of entry into the larynx, classically 0.5–1 cm below the inferior cornu of the thyroid cartilage • Use of the nerve-stimulator endotracheal tube (Xomed-Treace, Jacksonville, FL) can help detect the location of the RLN, especially in high risk situations:

– Large distorting tumors – Re-excision thyroidectomy – Severe post-radiotherapy fibrosis of the neck – Pre-existing VC paralysis in patients undergoing bilateral paratracheal node dissection

PREOPERATIVE ASSESSMENT • Diagnosis of potential VC palsy after head and neck surgery: – Ensure complete reversal of neuromuscular blockade to allow spontaneous ventilation at the conclusion of surgery – Extubate the patient while under deep inhalational anesthesia, followed by immediate insertion of a laryngeal mask airway – Use a fiberoptic bronchoscope to assess VC motion If adequate VC motion is present during regular breathing, deep breathing, coughing, and phonation as the patient emerges, the patient can be extubated If severe VC palsy is present, reintubate the patient for airway control and protection; administer IV steroids to decrease edema; consider a trial extubation after surgical edema has resolved; if repeated attempts at extubation fail, a tracheostomy should be performed • Diagnosis of pre-existing VC palsy as a co-morbid condition: By history, physical examination, and diagnostic procedures – History: Previous surgeries, intubations, and other causes of VC palsy – Ask about symptoms: Onset of voice changes, dyspnea, dysphagia – Physical examination: Assess the patient’s voice and listen for breathy voice, hoarseness. Assess the patient’s breathing; respirations may be stridorous – Examine the larynx by indirect mirror examination, direct and fiberoptic nasopharyngolaryngoscopy: Evaluate mucosa for scarring, subglottic stenosis, arytenoid mobility, VC asymmetry and motion – Videostrobolaryngoscopy: Provides additional information in cases of VC abnormalities when asymmetric mucosal wave patterns are present Uses pulses of light to study successive phases of VC activity Evaluates range and symmetry of motion of both VCs throughout their vibratory cycle – Laryngeal electromyography (EMG): Analyzes the electrical motor unit of the cricothyroid and thyroarytenoid muscles to test the SLN and RLN, respectively Distinguishes neuromuscular pathology from intrinsic VC and laryngeal joint pathology Performed at one month post-injury (baseline) and at two months post-injury (followup), this test helps to determine prognosis by evaluating VC recovery status – Pulmonary function tests and flow-volume loops: Findings are consistent with a variable extrathoracic airway obstruction (during spontaneous ventilation) Flattening of inspiratory loop Normal expiratory loop – CT scan from skull base to mediastinum: Helps to assess the entire trajectory of the vagus and recurrent laryngeal nerves to detect pathology

– MRI can be used in lieu of CT in pregnant patients, children, or patients with neurologic pathology

DIFFERENTIAL DIAGNOSES

• Cricoarytenoid joint ankylosis: Diagnosed by direct visualization during laryngoscopy and palpation of the suspected joint to rule out ankylosis causing VC immobility. Laryngeal EMG is also useful. • Angioneurotic edema involving the larynx • VC polyps, laryngeal tumors causing upper airway obstruction: Diagnosis confirmed by CT scans • Subglottic stenosis • Tracheal stenosis and tumors • Functional paradoxical VC motion: Diagnosed by documenting VC adduction during inspiration

TREATMENT • Voice exercises • Medical therapy: – Reflux management of GERD – Corticosteroids for inflammatory disorders affecting the larynx – Optimization of glucose management in DM neuropathy • Surgical therapy: – Unilateral VC palsy: Major concern is voice quality. If voice therapy does not provide satisfactory results, medialization can move the displaced and immobile VC toward midline Intracordal injection of teflon, collagen, autologous fat, calcium hydroxyapatite Selective re-innervation of the affected laryngeal muscles – Bilateral VC palsy: Major concern is airway obstruction Relieve obstruction and widen glottic aperture by tracheostomy Permanent procedures: Posterior cordotomy, arytenoidectomy, VC lateralization Experimental procedures: Nerve–muscle transfer to the posterior cricoarytenoid muscle, electrical pacing – Completely non-functional larynx with life-threatening recurrent aspiration pneumonias: Perform total laryngectomy as a last resort

FOLLOW-UP Spontaneous recovery occurs in 55% of patients with bilateral VC palsy; 50% of these patients recover within 1 year after initial diagnosis CLOSED CLAIMS DATA

VC paralysis accounts for 0.6% of total claims (25 out of 4,183 claims) from The ASA Closed Claims Project 1998

REFERENCES

1. Decker J, Deckert L. Vocal cord dysfunction. Am Fam Physician. 2010;81(2):156–159.

2. Dralle H, Sekulla C, Lorenz K, et al. Intraoperative monitoring of the recurrent laryngeal nerve in thyroid surgery. World J Surg. 2008;32:1358–1366. 3. Hillel AD, Benninger M, Blitzer A, et al. Evaluation and management of bilateral vocal cord immobility. Otolaryngol Head Neck Surg. 1999;121:760–765. 4. Jeannon JP, Orabi AA, Bruch GA, et al. Diagnosis of recurrent laryngeal nerve palsy after thyroidectomy: A systematic review. Int J Clin Pract. 2009;63:624–629.

5. Rubin AD, Sataloff RT. Vocal cord paresis and paralysis. Otolaryngol Clin North Am. 2007;40(5):1109–1131.

6. Sataloff RT, Praneetvatakul P, Heuer RJ, et al. Laryngeal electromyography: Clinical application. J Voice. 2010;24:228–234. See Also (Topic, Algorithm, Electronic Media Element) • Recurrent laryngeal nerve • Superior laryngeal nerve • Amyotrophic lateral sclerosis • Myasthenia gravis

CODES ICD9 • 478.30 Paralysis of vocal cords or larynx, unspecified • 478.31 Unilateral paralysis of vocal cords or larynx, partial • 478.32 Unilateral paralysis of vocal cords or larynx, complete ICD10 • J38.00 Paralysis of vocal cords and larynx, unspecified • J38.01 Paralysis of vocal cords and larynx, unilateral • J38.02 Paralysis of vocal cords and larynx, bilateral

CLINICAL PEARLS

• Special anesthetic considerations in patients with pre-existing VC paralysis presenting for general anesthesia: – Patients with known VC palsy are at risk for recurrent aspiration pneumonias; elective surgery should be undertaken only after resolution These patients should be intubated as atraumatically as possible. In patients with normal airways, direct laryngoscopy allows the benefit of direct vision during passage of the endotracheal tube through the glottis. In patients with difficult airways, fiberoptic laryngoscopy facilitates visualization of the VCs and trachea. Beware, however, that endotracheal tube passage over a bronchoscope through the VCs

is done blindly and may cause further trauma. – Be vigilant of the risk of injury to the affected VC during extubation; may cause respiratory obstruction or aspiration during emergence. • Special anesthetic considerations in patients presenting for VC medialization with monitored anesthetic care (MAC): – Procedure involves: Creation of a window in the thyroid ala cartilage Insertion of an implant in that window to medialize the affected VC Adjustment of VC medialization performed under fiberoptic visualization of affected VC motion with patient vocalization on command Fixation of implant in the optimal position – Anesthesia objectives: The patient should be comfortable during the creation of the cartilage window. The patient should be able to cooperate and phonate during the insertion and fixation portion of the procedure to help achieve optimal VC approximation. – Pharmacologic agents used: Prior airway nebulization with 4% lidocaine to decrease laryngeal reflexes Anticholinergics such as scopolamine or glycopyrrolate to help dry airway secretions Corticosteroids such as dexamethasone to decrease VC edema Antitussives such as codeine to decrease coughing during the procedure

VOLUME OF DISTRIBUTION Erik E. Abel, PharmD, BCPS Ravi S. Tripathi, MD

BASICS DESCRIPTION

• Pharmacokinetic (PK) parameters are the fundamental principles that dictate drug dose, dosing interval, and monitoring. • Multiple factors influence drug pharmacokinetic properties. They are typically divided into: – Absorption – Distribution – Metabolism – Elimination • Volume of distribution (Vd) is a theoretically derived PK parameter describing the association between serum drug concentrations relative to the amount of drug administered before metabolism and elimination occurs, or at steady state. – Degree and rate of distribution is commonly uneven due to differing tissue perfusion, tissue and protein-binding, and regional pH/temperature. – Each drug is uniquely distributed within the body and may be influenced considerably under pathophysiologic disease states. PHYSIOLOGY PRINCIPLES

• The Vd can be calculated by dividing the total amount of drug in the body by the drug’s blood plasma concentration.

• Units are in Liters/kg body weight • Small Vd suggests that the drug is mostly confined to the plasma; the value is similar to plasma volume • Large Vd suggests that the drug has more extensive spread to other tissues; the Vd exceeds the total plasma volume • Factors affecting Vd should be taken into account when determining dosing strategies: – Age The elderly population commonly has increases in body fat and decreased plasma volume, total body water, and extracellular body fluid. These factors increase the Vd of lipophilic drugs and decrease the Vd of non-lipophilic drugs. – Molecular charge and pH Dissociation constants (pKa) of drugs determine the charge of the molecule at

physiologic pH and temperatures. Acidic drugs in normal physiologic states tend to be highly protein bound (to albumin, a basic protein) and have relatively low Vd; they remain in the plasma. Basic drugs in normal physiologic states are typically taken up into tissues (muscle, adipose tissue, etc) and have a larger Vd. In the plasma, they bind to acidic proteins including alpha-1 acid glycoprotein (AAG) and lipoproteins. Dissociation constants play a role in determining solubility, tissue-binding affinity, and membrane permeability of a drug in various physiologic conditions. – Temperature Can affect the molecular charge of molecules as well as the relative affinity of a molecule for a given receptor. For example, the affinity of morphine to bind to a mu-receptor decreases as temperature decreases; potency at 30°C is one-fifth that of that at 37°C (1). Metabolism by enzymatically catalyzed reactions. Metabolic rates can decrease by 50% for every 10°C decrease in temperature (1). Additionally, the glomerular filtration rate also decreases and can contribute to decreased clearance. – Total body water Increased in pregnancy, children, infants, and neonates. Critical illness and some chronic illnesses (congestive heart failure, renal disease, liver disease) are also commonly associated with an increased Vd due to increases in total body water and decreases in plasma protein levels (decreased production or increased loss). – Protein binding Drugs may bind to plasma proteins, decreasing the free fraction of the unbound drug that is circulating and decreases redistribution into other compartments. Highly protein-bound drugs (e.g., phenytoin) should be more conservatively dosed in cachectic patients compared to normal patients, as free/unbound drug concentrations will be more easily achieved. – Adipose tissue Lipophilic drugs will readily distribute into these tissues and have a large Vd. Once the adipose sites are saturated, drug elimination occurs at a slower rate due to poor perfusion of these tissues. – Extracorporeal circulation Dosing strategies must consider the impact of extracorporeal circulation on PK parameters. Most circuits have tubing that creates a binding/adsorptive potential for drug sequestration. With renal replacement therapy, depending on the route of elimination and dialysis filter used, there can be significant decreases to drug clearance. Cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation or life support (ECMO or ECLS) will increase the Vd of most drugs; however, the impact of various oxygenators on drug disposition is less studied since this technology has advanced. – Gender One of the most important influences on Vd when considering body composition, body mass index (BMI), plasma volume, and organ perfusion.

In females, the total body weight, BMI, and plasma volume are typically lower, whereas organ perfusion and proportion of body fat are typically higher compared to males. Additionally, endogenous estrogens decrease AAG concentrations and hence binding to basic drugs (may have increased Vd) (2).

ANATOMY

• Blood–brain barrier (BBB) (3). – Drug penetration into the CNS is highly limited as a result of endothelial tight junctions. – Factors favoring BBB penetration Non-charged molecules (non-ionized) Low protein binding High lipophilicity Small molecules (<500 Daltons) – The BBB may become more penetrable with increased age and in states of inflammation. • Placental barrier (PB) – Changes as the fetus matures; syncytiotrophoblasts contribute considerably to the PB. – Maintains a tight barrier to large molecules while allowing for gas exchange, electrolyte and acid–base balance, and nutrient delivery.

DISEASE/PATHOPHYSIOLOGY

• Profound acid-base imbalances can have significant changes on the Vd of drugs (e.g., septic shock, diabetic ketoacidosis, hypercarbic respiratory failure). Critically ill patients may have extreme sensitivity to many drugs. Consider decreasing induction agent doses and other perioperative medications. • Acid-base imbalances can lead to increased vasopressor/inotropic requirements to achieve the same effect. • Low protein states: The lack of available proteins for binding requires decreased dosing to reach the same effect as compared to healthy patients, particularly with highly proteinbound drugs. In the perioperative period, it may be seen in patients with: – Liver disease – Nephrotic syndrome – Congestive heart failure – Protein-losing enteropathy – Malnutrition • Obesity can have a significant effect on the Vd of drugs. – For bolus dosing, most drugs should be dosed based on ideal body weight.

PERIOPERATIVE RELEVANCE

• CPB represents similar PK challenges as ECMO (4). – The circulating blood volume may vary significantly during the operation. – Temperature can vary greatly during CPB and affect the molecular charge/receptor binding of drugs. In addition to decreasing metabolism by the liver and kidneys, drugs that have organ-independent metabolism (e.g., atracurium/cisatracurium) also have decreased clearance. – pH can vary by tissue region depending on perfusion to that area.

– Hemoconcentrators may increase clearance. • Patients suffering from hemorrhagic shock may have profound changes in Vd. – The blood loss may be associated with a significant decrease in protein concentrations. – Additional protein loss may be associated with cell salvaging techniques during the washing and processing stage. – Large blood loss may require re-dosing of antibiotics.

EQUATIONS

• LD = Css × Vd

– LD: Loading dose – Css: Desired concentration at steady state (units of serum concentration level to determine

dosing unit) • Vd: Volume of distribution of a given drug (typically L/kg) × patient weight (kg)

GRAPHS/FIGURES See Table

REFERENCES

1. Tortorici MA, Kochanek PM, Poloyac SM. Effects of hypothermia on drug disposition, metabolism, and response: A focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system. Crit Care Med. 2007;35(9):2196–2204. 2. Gandhi M, Aweeka F, Greenblatt RM, et al. Sex differences in pharmacokinetics and pharmacodynamics. Annu Rev Pharmacol Toxicol. 2004;44:499–523. 3. Pardridge WM. Blood-brain barrier drug targeting: The future of brain drug development. Mol Interv. 2003;3(2):90–105, 51. 4. Mets B. The pharmacokinetics of anesthetic drugs and adjuvants during cardiopulmonary bypass. Acta Anaesthesiol Scand. 2000;44(3):261–273.

ADDITIONAL READING

• Bauer LA. Applied clinical pharmacokinetics. 1st ed. McGraw-Hill Medical; 2001.

See Also (Topic, Algorithm, Electronic Media Element) • Context sensitive half life • End stage liver disease • Cell savage • Chronic renal failure

CLINICAL PEARLS

• Changes in Vd can affect the dosing and clinical effects of most anesthetic agents. • Neonates, gravid women, and patients with cardiac, renal, and liver disease are prone to changes in Vd and may require dosing adjustments.

VON WILLEBRAND’S DISEASE Annie D. Lee, MD Judith A. Turner, MD, PhD

BASICS DESCRIPTION

• von Willebrand’s disease (vWD) is the most common inherited bleeding disorder; it can result from either defective or low levels of von Willebrand factor (vWf) • vWF: – Is an adhesive glycoprotein – Functions in primary (platelet adhesion) and secondary (clot formation) hemostasis – Serves as a stabilizer for Factor VIII, another protein in the coagulation cascade • There are 3 major types of disease with type-specific morbidity, mortality, and treatments: See classification below for details EPIDEMIOLOGY Prevalence

Males and females are affected equally Prevalence

• Worldwide: 0.57–1.15% • Type 1: ∼70–80% of all cases • Type 2: ∼15–20% of all cases. Type 2A is the most common subtype in this class • Type 3: Very rare

Morbidity

Variable, depends on type Mortality

Depends on severity of disease ETIOLOGY/RISK FACTORS

• vWD is the result of a gene mutation on chromosome 12 • Type 1: Autosomal dominant disorder with variable penetrance • Type 2: Autosomal dominant or recessive • Type 3: Homozygous for severe form, heterozygotes may have a less severe form • Blood type O: Regardless of vWD, in the general population, patients with type O blood can have a 25–30% decreased level of vWf, likely secondary to increased clearance. PHYSIOLOGY/PATHOPHYSIOLOGY

• vWf is produced and stored in megakaryocytes and endothelial cells (when injured, it

exposes vWf and helps begin the clotting, immediately). • Primary hemostasis: vWf binds to the platelet’s surface receptor glycoprotein Ib and activates it. The ‘activated’ platelet will: – Adhere and aggregate to other platelets – Adhere to the vessel wall • Secondary hemostasis: vWf binds Factor VIII and chaperones it to sites of vascular injury; it also stabilizes and increases Factor VIII’s half-life • Thus, defective or low levels of vWf lead to increased bleeding risk, secondary to impaired platelet adhesion and coagulation

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Determine the need for pre-treatment of vWD and/or blood transfusion for increased bleeding risk during surgery or peripartum • Hematology consultation may be useful in cases of recent diagnosis or prolonged major surgery and should be performed weeks prior, if possible. Patients with severe disease are often under the care of a hematologist • Careful assessment of the severity of vWD should be performed prior to employing a regional technique

PREOPERATIVE ASSESSMENT SYMPTOMS

• Mild–moderate: Easy bruising, epistaxis, gum bleeding, menorrhagia, melena/hematochezia, hematuria • Severe: Hemarthrosis, spontaneous uncontrolled bleeding

History

• Family history of bleeding disorder or easy bleeding • Blood transfusion or significant bleeding disproportional to a procedure

Signs/Physical Exam

• Evidence of unusual bleeding, large bruising, hemarthrosis (severe joint pain and swelling) • Severe anemia • Thrombocytopenia • Liver disease

TREATMENT HISTORY

Cryoprecipitate (CPT) may be used to manage acute bleeding. Fresh frozen plasma (FFP) can also be used but large volumes may be required to achieve hemostasis MEDICATIONS

• Desmopressin (DDAVP): First-line therapy for Types 1 and 2A: 0.3 mcg/kg IV in 30–50 mL NS over 30 minutes or nasal spray; stimulates endothelial cell release of vWf (also increases Factor VIII by unknown mechanism). May be re-dosed every 12–24 hours as needed, but tachyphylaxis can occur.

– Cardiovascular disease may contraindicate its use – Safe in pregnancy, as it does not significantly cross the placenta. – Do not administer to children aged <2 years – Has been traditionally contraindicated in Type 2B due to DDAVP-induced thrombocytopenia; however, there have been reported cases of its clinical benefit. A test dose with platelet monitoring should be performed prior to surgery • vWf replacement therapy: Second-line for Types 1–2; may be considered first-line for Types 2–3 as these may not respond to DDAVP. Typically in the form of Factor VIII concentrates with vWf in varying amounts (i.e., Haemate-P, Alphanate, BPL8Y). VHP-VWF is a vWf concentrate available only in France • IVIG: Third-line therapy (1 g/kg × 2 days) for inherited disease, but may also be used for acquired vWD • Antifibrinolytics (e.g., aminocaproic acid or tranexamic acid) may be considered • Fibrin glue on the surgical field may be helpful • Treatment for menorrhagia: Combined oral contraceptives, levonorgestrel intrauterine device

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• vWf antigen (amount of vWf; “quantitative”) • vWf ristocetin cofactor activity (vWf-RCo – functionality of vWf) • vWf multimers (structure of vWf) • PTT: Prolonged in patients with significantly low Factor VIII • Platelet tests: Platelet counts only provide quantitative measures, not qualitative. Functional tests include aggregometry, flow cytometrics, thromboelastography (TEG), among many others. Details are beyond the scope of this discussion • Type and screen/cross: There are no specific guidelines but a type and screen is recommended for all surgical cases (clinical judgment can be used for minor, superficial surgeries) and type and cross for any major surgery or any surgery with potential for large blood loss.

CIRCUMSTANCES TO DELAY/CONDITIONS

• Minor bleeding: Delay surgery for 1–5 days after hemostasis • Major bleeding: Delay 7–14 days after hemostasis

CLASSIFICATIONS

• Type 1: Low levels of vWf; mildest form of disease • Type 2: Defective and low levels of vWf – Type 2A (most common) demonstrates abnormal, high molecular weight multimer complexes that are responsible for platelet binding (qualitative), decreased levels of vWF (quantitative), as well as decreased levels of Factor VIII – Type 2B demonstrates a decrease in high molecular weight multimer complexes (qualitative) with a resultant increase in affinity for platelet glycoprotein Ib, as well as intermittent thrombocytopenia • Type 3: No vWf, low levels of Factor VIII (most serious, rare)

• Acquired: Associated with cardiac valvular diseases, angiodysplasia, thrombocytosis, hypothyroidism

TREATMENT Pregnancy Considerations

• Despite a physiologic increase in vWf and Factor VIII, patients with vWD still have a higher bleeding risk peripartum. In addition, a physiologic decrease in platelets may be seen • Check vWf:RCo and Factor VIII levels prior to any invasive procedure and, at a minimum, once in the third trimester. Prior to childbirth, levels of both should be >50 IU/dL and maintained 3–5 days after (daily testing is recommended to prevent/decrease the risk of postpartum hemorrhage). Although there is no consensus, some experts consider this a “safe” level for regional anesthesias • Consider prophylaxis with CPT, FFP, DDAVP, and factor replacement after balancing the risks and benefits of each • Continue monitoring and/or treatment at least 2 weeks postpartum due to a risk of delayed hemorrhage PREOPERATIVE PREPARATION Premedications

DDAVP, FFP, or factor placement may be recommended by the hematologist and/or in urgent/emergent procedures Pediatric Considerations

No DDAVP for children <2 years old Geriatric Considerations

• Prior to DDAVP administration, evaluate for cardiovascular diseases due to an increased risk of myocardial infarction • Electrolytes should also be monitored

Special Concerns for Informed Consent

• Increased bleeding risk • Possible need for blood product transfusion

INTRAOPERATIVE CARE Choice of Anesthesia

Risk of bleeding from neuraxial technique must be carefully considered and possibly avoided if the risks exceed potential benefits Monitors

Consider central access for fluid and blood management for higher risk procedure with the potential for significant blood loss. Consider the use of ultrasound imaging to decrease the chance of inadvertent arterial puncture as well as accessing the internal jugular or femoral

veins as they can be more easily compressed than the subclavian vein. Induction/Airway Management

Careful instrumentation with airway devices to avoid bleeding Maintenance

Careful fluid management and monitoring of blood loss with transfusion of vWf-containing concentrates and/or packed red blood cells (pRBCs) as indicated. In addition, DDAVP may result in “water intoxication,” via its antidiuretic action at the level of the renal collecting ducts Extubation/Emergence

Consider the use of an airway exchange catheter if there is concern about airway bleeding in the immediate extubation period.

FOLLOW-UP BED ACUITY

Determined by fluid shifts during procedure MEDICATIONS/LAB STUDIES/CONSULTS

• Hematology consult may be appropriate, especially in patients with vWD Type 3 • Careful monitoring of CBC, coagulation, vWf:RCo and Factor VIII; electrolytes if using DDAVP • Medication adverse effects

COMPLICATIONS

• DDAVP may be associated with hypotension, hyponatremia, and increased risk of myocardial infarction in patients with coronary artery disease • Excessive transfusion of Factor VIII has been associated with thromboembolism • Transfusion-related risk: Infection, immune-mediated

REFERENCES

1. Hambleton J. Diagnosis and incidence of inherited von Willebrand disease. Curr Opin Hematol. 2001;8(5):306–311. 2. Pasi KJ, Collins PW, Keeling DM, et al. Management of von Willebrand disease: A guideline from the UK Haemophilia Centre Doctor’s Organization. Haemophilia. 2004;10(3):218– 231. 3. Stedeford JC, Pittman JA. Von Willebrand’s disease and neuraxial anaesthesia. Anaesthesia. 2000;55(12):1228–1229. 4. Kadir RA, Lee CA, Sabin CA, et al. Pregnancy in women with von Willebrand’s disease or factor XI deficiency. Br J Obstet Gynaecol. 1998;105(3):314–321. 5. Pacheco LD, Constantine MM, Saade GR, et al. von Willebrand disease and pregnancy: A

practical approach for the diagnosis and treatment. Am J Obstet Gynecol. 2010;203(3):194–200. 6. Bowman M, Hopman WM, Rapson D, et al. The prevalence of symptomatic von Willebrand disease in primary care practice. Thromb Haemost. 2010;8(1):213–216.

7. Laffan M, Brown SA, Colins PW, et al. The diagnosis of von Willebrand disease: A guidelines from the UK Haemophilia Centre Doctor’s Organization. Haemophilia. 2004;10(3):199–217.

8. Castaman G, Tosetto A, Eikenboom JC, et al. Blood group significantly influences von Willebrand factor increase and half-life after desmopressin in von Willebrand disease Vicenza. Thromb Haemost. 2010;8(9):2078–2080. 9. Federici AB. The use of desmopressin in von willebrand disease: The experience of the first 30 years (1977–2007). Haemophilia. 2008;14(Suppl 1):5–14.

ADDITIONAL READING

• http://www.nhlbi.nih.gov/guidelines/vwd/4_managementofvwd.htm See Also (Topic, Algorithm, Electronic Media Element) • Cryoprecipitate • Fresh frozen plasma • Thrombocytopenia

CODES ICD9 286.4 Von Willebrand’s disease ICD10 D68.0 Von Willebrand’s disease

CLINICAL PEARLS

• Consider early consultation with a hematologist to determine the most appropriate interventions • Factor VIII is the best predictor of bleeding complications • DDAVP is first-line therapy for vWD Types 1 and 2A; may be associated with DDAVPinduced thrombocytopenia in Type 2B; Type 3 is unresponsive to DDAVP

WHIPPLE PROCEDURE

Vijaya Gottumukkala, MB, BS, MD, FRCA

BASICS DESCRIPTION General

• The Whipple procedure was originally described by Alessandro Codivilla, an Italian surgeon, in 1898. However, the procedure is named after Allen Oldfather Whipple (1881–1963), an American surgeon, who perfected the technique and subsequently devised multiple modifications and variants. • The Whipple procedure, either in the classic or variant approach, may be performed for the resection of: – Pancreatic adenocarcinoma – Endocrine tumors – Tumors involving the duodenum, ampulla of Vater, common bile duct – Chronic pancreatitis that is refractory to medical treatment – Traumatic injury to the pancreas • Carcinoma of the pancreas usually arises from epithelial cells of the ductal system in the exocrine part of the gland. Histologically, the majority are adenocarcinomas with varying degrees of mucin production; 60–70% of all pancreatic adenocarcinomas arise in the head of the pancreas. • Despite advances in chemotherapy, resection alone offers a potential cure. However, because pancreatic cancer is usually recognized late and local advancement is likely, it has a poor long-term outcome regardless of treatment modality. Chemo-radiation is usually used as an adjunct therapy to surgical resection. • The Whipple procedure consists of en-bloc removal of the: – Antrum (distal half of the stomach) – Gallbladder – Head of the pancreas – Duodenum – Proximal jejunum – Regional lymph nodes • Reconstruction consists of attaching: – The pancreas to the jejunum (pancreaticojejunostomy) – The hepatic duct to the jejunum (hepaticojejunostomy) – The stomach to the jejunum (gastrojejunostomy) • Gastrostomy and jejunostomy tubes are usually placed to facilitate gastric emptying and enteral nutrition. Position

• Supine

• If the internal jugular vein is needed for reconstruction of the portal vein, the head is rotated to the right and the left groin is prepped.

Incision

Midline abdominal or bilateral subcostal (“Chevron incision”) Approximate Time

5–10 hours (depending on the need for vascular reconstruction) EBL Expected

500–1,500 mL Hospital Stay 7–10 days

Special Equipment for Surgery

• Laparoscopic equipment (if diagnostic laparoscopy is needed to evaluate peritoneal/hepatic dissemination prior to surgery) • Biliary stent • Vascular set

EPIDEMIOLOGY Prevalence

In 2010, >43,000 individuals in the U S were diagnosed with pancreatic cancer, and 36,800 have died from the disease. Prevalence

• An increased risk for pancreatic cancer has been associated with smoking, advanced age, male gender, and a close relative with the diagnosis. • On January 1, 2007, there were ∼32,993 men and women living in the US with a history of pancreatic cancer • On the basis of rates from 2005–2007, 1.41% of men and women born today will be diagnosed with cancer of the pancreas at some time during their lifetime.

Morbidity

See Complications Mortality

• 30-day in-hospital mortality is <2% in high volume centers • Pancreatic cancer accounts for 5% of all cancer-related deaths, and is the fifth leading cause of death in the US population.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Patient population with significant comorbidities (age, smoking, diabetes, hypertension, atherosclerosis, coronary artery disease, malnutrition): Optimize preoperative comorbid burden for optimal postoperative recovery

• Effective analgesia (epidural preferred) • Extubation at the end of surgery • Maintenance of euvolemia • Postoperative monitoring in a high dependency unit for 48 hours • Patients with acute pancreatitis may be septic, severely hypovolemic, have a high risk for respiratory complications (ARDS, pleural effusions), or present with hypocalcemia.

PREOPERATIVE ASSESSMENT SYMPTOMS

• Varies by underlying condition necessitating procedure. • Symptoms of pancreatic cancer are usually non-specific and may include nausea, anorexia, jaundice, weight loss, and abdominal pain. Other less common symptoms include diarrhea, steatorrhea, glucose intolerance, and depression. • May have flushing, syncopal episodes, diarrhea, and wheezing if associated with a neuroendocrine or carcinoid pathology.

History

• Varies by the underlying condition necessitating the procedure. • Pancreatic cancer is usually diagnosed following a workup for vague symptoms, abdominal pain, or jaundice • Careful assessment of comorbidities, nutritional and functional status

Signs/Physical Exam

• Non-specific • Flushing, bronchospasm, jaundice with duodenal carcinoid tumors

MEDICATIONS Analgesics

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• LFT, creatinine, prealbumin • CBC, PT/PTT • Electrolytes if on diuretics, ACE I, renal insufficiency • Helical CT scan (tumor size, vascular involvement, peritoneal and liver metastasis) • Upper GI endoscopy with or without ERCP • Other tests (TEG, ECG, CXR, echocardiogram, exercise stress test, PFTs) as indicated by comorbidities

CONCOMITANT ORGAN DYSFUNCTION • Diabetes • Hypertension • Coronary artery disease

• Obesity/malnutrition • Right heart valvular lesions with carcinoid syndrome

TREATMENT PREOPERATIVE PREPARATION Premedications

• Anxiolytic and analgesic medication as needed • Gastric juice volume reducing and acid neutralizing medications if indicated. • Crystalloid fluid bolus for prolonged fasting or bowel prep, as deemed appropriate. • Continue appropriate anti-hypertensive, anti-arrhythmic, and other medications as needed • Continue somatostatin analogs if carcinoid pathology is present

Special Concerns for Informed Consent

• Blood consent for possible transfusion • Epidural catheter placement for postoperative analgesia • Potential for postoperative intubation and intensive care

Antibiotics/Common Organisms

• Skin organisms; cefazolin • In patients with acute pancreatitis, continue with current regimen

INTRAOPERATIVE CARE Choice of Anesthesia

• General anesthesia with ETT • Epidural catheter (T6–T10, depending on incision) for postoperative analgesia: Need to rule out contraindications, review medication list (herbal, clopidogrel, low molecular weight heparins, or other drugs that alter coagulation), consider preoperative PT/PTT/INR or other advanced coagulation tests as needed (TEG, PFA). Not contraindicated with usual thromboprophylaxis for postoperative DVT or intraoperative heparinization for vein reconstruction. Monitors

• ASA standard monitors • Arterial line (beat-to-beat BP monitoring, systolic pressure variation [SPV] to evaluate intravascular volume status, blood draws for lab work), consider awake A-line pre-induction in high-risk patients or with carcinoid pathology • Non-invasive cardiac output monitors (On the basis of pulse-contour analysis [stroke volume variation, SVV] or Doppler flow measurements in descending aorta [Flow corrected time, FTc]) may be a useful adjunct to evaluate hemodynamic function and intravascular volume status (be aware of the limitations of each of the technologies) (4) • 2 large-bore IVs (14/16 g) for volume resuscitation if needed. Central line access not usually necessary unless there is poor IV access • Foley catheter

Induction/Airway Management

• Standard induction techniques; adjust strategies as needed to maintain hemodynamic stability and prevent aspiration in patients at risk. • Cuffed endotracheal tube allows airway protection and the ability to institute positive pressure ventilation with surgical retraction (decreased airway compliance).

Maintenance

• Avoid nitrous oxide. Air–oxygen mixture with an FiO2 of 0.5 will help identify oxygenation

issues early. • Nasogastric tube placement may be requested • Volume: Whipple is a major procedure with complex bowel and visceral resection; insensible losses can be significant. Intravascular volume status should be carefully monitored. • Continuous epidural infusion of local anesthetic/narcotic mixture can be used throughout the procedure. • Periodic blood glucose measurements should be performed as patients can get hyperglycemic during pancreatic manipulation. Extubation/Emergence

• Standard extubation criteria • Post-extubation sensory-motor examination and evaluation of epidural puncture site for effectiveness and complications

FOLLOW-UP BED ACUITY

• High dependency unit or ICU for 48 hours • May need monitoring of invasive hemodynamic parameters to guide fluid volume/blood product transfusion • Close monitoring of blood glucose, and treatment as warranted

ANALGESIA

• Epidural is the recommended approach • Multimodal approach involving an IV PCA if an epidural is contraindicated • Follow ASRA guidelines for maintenance and removal of epidural catheters

COMPLICATIONS

• Inadequate pain control • Early postoperative glucose intolerance • Adverse cardiac events (hypotension, hypertension, arrhythmias, ischemia, infarct, and CHF) • Postoperative fever and leukocytosis are not uncommon • Postoperative ileus • Delayed gastric emptying (20%), anastomotic leaks (15%): Pancreaticojejunostomy most common, wound infections (10%)

• Postoperative delirium in the elderly • Epidural site infection or hematoma (very rare)

PROGNOSIS

High incidence of local recurrence despite margin-free resection

REFERENCES

1. shuis WJ.Early postoperative hyperglycemia is associated with postoperative complications after pancreatoduodenectomy. Ann Surg. 2011;253(4): 739–744.

2. House MG, Fong Y, Amaoutakis DJ, et al. Preoperative predictors for complications after pancreaticoduodenectomy: Impact of BMI and body fat distribution. Gastrointest Surg. 2008;12:270–278.

3. Badger SA. The role of surgery for pancreatic cancer: A 12-year review of patient outcome. Ulster Med J. 2010;79(2):70–75. 4. Green D. Latest developments in the peri-operative monitoring of the high risk surgical patient. Int Surg. 2010;8(2):90–99.

ADDITIONAL READING

• American Cancer Society. Cancer Facts and Figures 2010. Atlanta, GA: American Cancer Society, 2010.

See Also (Topic, Algorithm, Electronic Media Element) • Epidural • International nationalized ratio • Diabetes mellitus • Insensible fluid losses • Carcinoid

CLINICAL PEARLS

• The Whipple procedure is a major bowel and visceral resection surgery that may require significant blood products and fluid resuscitation. • Overall long-term survival for pancreatic cancer is still very low (median survival 20–25 months), even after a successful resection (3). • Preoperative BMI and body fat distribution is considered to be a predictor for outcome (2). • Early postoperative hyperglycemia and wide fluctuation in blood glucose levels is a prognostic indicator for morbidity (1). • Patients are prone to the development of late DVT.

WOLFF–PARKINSON–WHITE SYNDROME Marc A. Logarta, MD, DABA, FANZCA

BASICS DESCRIPTION

• Wolff–Parkinson–White syndrome (WPW) describes an abnormal, early, ventricular muscle depolarization via an accessory pathway that exists outside of the atrioventricular nodal conduction system. • Labeled as a pre-excitation syndrome; patients are at risk of developing paroxysmal supraventricular tachycardia (PSVT) or atrial fibrillation (AF). • Beta-blockers and calcium channel blockers should be avoided perioperatively. They block normal antegrade AV nodal conduction and can “divert" electrical impulse through the accessory pathway. EPIDEMIOLOGY Prevalence

US population: 0.15–0.5% Morbidity/Mortality

• Frequent and disabling SVT: 40–80% • Sudden death: 0–0.4% per year

ETIOLOGY/RISK FACTORS

• Male sex (60–70% of patients) • Ebstein’s anomaly • Atrial and ventricular septal defects • Tricuspid atresia • Corrected transposition of the great vessels

PHYSIOLOGY/PATHOPHYSIOLOGY

• Sinoatrial (SA) to atrioventricular (AV) node conduction: The cardiac action potential is initiated in the SA node; the signal spreads through the right and left atria via the anterior, middle, and posterior interatrial/internodal tracts to the AV node. Adjacent myocardial cells are depolarized in a domino fashion with electrical depolarization followed by mechanical contraction and blood being pumped into the ventricles. • Pacemaker and conduction tracts have a different histology than myocardial cells. They are capable of spontaneous depolarization as well as speedy and expedient transmission of electrical signals. • AV node: When the electrical signal arrives at the AV node, there is a physiologic pause that allows for atrial emptying into the ventricle. In normal conditions, the AV node–bundle of His is the only connection between the atria and ventricles; all electrical signals must pass

into the ventricle in this manner. The surrounding fibrous skeleton is inert and prevents what would otherwise be widespread, unorganized depolarization of the ventricles. • AV node to Purkinje fibers: Following the AV nodal pause (akin to a speed bump), the electrical signal passes to the bundle of His; depolarization is accelerated and divided into the left and right bundle branches. Adjacent ventricular myocardial cells depolarize in a domino fashion, followed by contraction and blood ejection. • In WPW and other pre-excitation syndromes, abnormal accessory pathways exist and function as connections between the atria and ventricles (a shortcut via a fast highway). – These electrically active tracts are anomalous, embryonic remnants that bridge the otherwise inert fibrous cardiac skeleton and allow atrioventricular depolarization outside of the conventional SA–AV nodal pathway. – In WPW, these fibers are referred to as the bundle of Kent. – After an SA node impulse is initiated, the electrical signal travels to the AV node as well as to the accessory pathway. While the impulse is slowed down by the AV node “speed bump,” it is not hindered along the accessory pathway. Consequently, a small part of the ventricle is depolarized through the accessory pathway earlier than the bulk of the ventricle that is depolarized through the conventional AV–His–Purkinje pathway. • EKG: The fusion of two conducted waves alters ventricular depolarization and manifests as the delta wave on the ECG, which widens the QRS complex (>0.1 seconds). The PR interval is also shortened (<0.12 seconds); due to the “shortcut” taken via the accessory tract. – Right side pathway: Appears similar to a left bundle branch block. – Left side pathway: May appear similar to a right bundle branch block. – In some cases it may be “concealed” • Dysrhythmias: Although most patients with WPW will be in sinus rhythm, recurrent tachycardias may manifest (70% PSVT, 30% AF). PSVT is either orthodromic or antidromic. • PSVT–orthodromic tachycardia (95%); ventricles are depolarized normally in an antegrade fashion via the AV nodal tract. However, subsequent atrial depolarization is not initiated by the SA node, but by retrograde conduction from the accessory pathways (ventricle to atria). – If a premature atrial impulse occurs and is conducted normally through the AV node, but the bundle of Kent is still refractory, there will be a “normal” ventricular depolarization. – However, as the impulse passes through the conventional AV–His–Purkinje pathway, it will once again encounter the bundle of Kent (in the ventricle) which will now be out of its refractory period. – The impulse will travel in a retrograde manner back into the atria and toward the AV node again. – If this self-sustaining “circus rhythm” is established, it will result in PSVT. The QRS complex will appear narrow because ventricular depolarization originates at the AV node, and the delta wave will disappear because antegrade conduction passes entirely through the AV node. • PSVT–antidromic tachycardia (5%): Atrial conduction to the ventricles is via the accessory node. Subsequent atrial depolarization occurs from retrograde transmission from the ventricles to the atria via the AV node. – If a premature atrial impulse occurs and finds the AV node refractory but the bundle of Kent is receptive to depolarization, the electrical signal will travel to the ventricles

through the accessory pathway. – It will travel in a retrograde manner through the Purkinje–His–AV nodal pathway, back into the atria only to encounter the bundle of Kent again. – If the circus rhythm establishes itself, it will result in a PSVT with wide-complex QRS intervals. • Atrial fibrillation: Although not necessarily caused by WPW, if it occurs in a patient with WPW, it can result in severe hemodynamic compromise. Without the AV node to act as a gate-keeper between the atria and ventricles, ventricular rates may rise to 300 beats/min and has been reported to degenerate into ventricular fibrillation.

ANESTHETIC GOALS/GUIDING PRINCIPLES

• Catheter radiofrequency ablation is the treatment of choice. For patients who are not candidates for ablation, pharmacologic therapy is most often instituted. • Preoperative preparation should include a review of the cardiologic studies and when possible, consultation with the cardiologist. • Avoidance of anxiety and other stimulating factors as well as preparation to treat a tachyarrhythmia should be made.

PREOPERATIVE ASSESSMENT SYMPTOMS

Patients are mostly asymptomatic; however, 50% will present with symptoms at some stage such as palpitations, chest discomfort, syncope, heart failure, and possibly cardiac arrest History

• Onset • Therapeutic modalities • In some patients, WPW may first present on a preoperative electrocardiogram.

Signs/Physical Exam

• Tachycardia (∼250–300 beats/min) • If experiencing a dysrhythmia, may be cool and diaphoretic • Bilateral crackles may be present if the patient develops pulmonary edema

MEDICATIONS

• Chronic pharmacologic therapy is often implemented for patients who have failed ablation or who are not candidates for ablation. • Orthodromic AV re-entrant tachycardia treatment includes quinidine, disopyramide, procainamide and propafenone. Second-line agents have specific AV nodal activity (calcium channel blockers, beta-blockers, digoxin) • Antidromic AV re-entrant tachycardia treatment includes flecainide and propafenone. • Amiodarone can be used for both orthodromic and antidromic AV reentrant tachycardias, but may not be desirable because of long-term side effects (pulmonary, thyroid) • Anti-arrhythmics should be continued perioperatively for non-ablative procedures (often discontinued for ablation in an attempt to elicit arrhythmias).

DIAGNOSTIC TESTS & INTERPRETATION Labs/Studies

• Consider electrolyte panel; abnormalities may predispose to tachyarrhythmias • Thyroid function studies may be considered if on amiodarone • ECG: Morphology is based upon the location of the bundle of Kent. Preoperative EKGs may actually be the first presenting abnormality • Electrophysiologic testing can locate the bypass tract. There is no reliable method to preoperatively identify the subgroup of patients who are prone to progression to ventricular fibrillation with EP testing.

CONCOMITANT ORGAN DYSFUNCTION

∼10% of patients will have other cardiac diseases (atrial septal defect, Ebstein’s anomaly, tricuspid atresia, corrected transposition of the great vessels, ventricular septal defect). CIRCUMSTANCES TO DELAY/CONDITIONS • Symptomatic arrhythmia • Congestive heart failure

CLASSIFICATIONS

• Orthodromic tachycardia (95%) • Antidromic tachycardia (5%)

TREATMENT PREOPERATIVE PREPARATION Premedications

Anxiolysis as needed to avoid increases in catecholamine levels INTRAOPERATIVE CARE Choice of Anesthesia

• Both general and regional anesthetic techniques have been used in WPW. Management should be centered around decreasing factors that can increase sympathetic outflow (decreasing refractoriness of accessory pathways). • Synchronized cardioversion and defibrillation should be readily available.

Monitors

• Electrocardiographic monitoring should be optimal for the diagnosis of supraventricular arrhythmias (Leads II and V1) • Consider the application of external pads and connection to a cardioverter/defibrillator, especially for electrophysiologic studies. • Consider an arterial line in high-risk patients • If the patient needs a central line placed for surgical or medical reasons, care should be taken upon placement (episodes of SVT have been reported as guide wires have been

advanced into the atria).

Induction/Airway Management

• Induction of anesthesia with intravenous agents such as propofol or etomidate should be titrated to attenuate the sympathetic response to laryngoscopy and intubation. The literature is mixed about the change in refractory period in response to thiopentone. • Intubation should only be attempted once the airway and hemodynamic reflexes are sufficiently blunted. • Fentanyl has been shown to have no effect on the accessory pathway. • Succinylcholine and most drugs causing non-depolarizing muscle blockade are safe in WPW. • Avoid drugs that may increase sympathetic nervous system activity such as ketamine and pancuronium.

Maintenance

• Keep the patient adequately anesthetized. • All modern volatiles have been used in WPW, although some advise against the use of desflurane.

Extubation/Emergence

• Consider “deep” extubation • Avoid anticholinesterases

FOLLOW-UP BED ACUITY

• Vigilance for dysrhythmias • Consider a monitored bed if the patient has had any evidence of tachyarrhythmias or if major surgery was performed • Optimize pain control

COMPLICATIONS

• Cardiac arrest and hemodynamically unstable patients should be treated as per advanced cardiac life support (ACLS) guidelines. • Supraventricular tachycardia (SVT) – Vagal stimulation intraoperatively may not be effective and may delay more definitive treatment. – If hemodynamically stable and in a regular, narrow complex tachycardia, adenosine 6 mg fast IV push should be considered. Electrical cardioversion/defibrillation should be readily available. – If hemodynamically stable and in a regular, broad complex tachycardia, procainamide (17 mg/kg) or amiodarone 150 mg over 10 minutes can be given. For known antidromic AV re-entrant tachycardia, the drug of choice for acute termination is procainamide. Even if the tachycardia is not immediately terminated, the hemodynamic state may improve. • Atrial fibrillation (AF) – AV-node specific antiarrhythmic drugs that are ordinarily used in non-pre-excited AF

(beta-blockers, verapamil, digoxin, adenosine) are contraindicated. Verapamil has been known to precipitate cardiac arrest in patients with known WPW with AF conducted through the bundle of Kent. – Procainamide is the drug of choice for acute therapy in the US.

REFERENCES

1. Irish CL, Murkin JM, Guiraudon GM. Anaesthetic management for surgical cryoablation of accessory conducting pathways: A review and report of 181 cases. Can J Anaesth. 1988;35(6):634–640.

2. Goldhill DR, Latosa ED, Facer E. Anaesthesia and Wolff-Parkinson-White syndrome during infancy: A review. J R Soc Med. 1988;81(6):345–347.

ADDITIONAL READING

• www.uptodate.com. Pharmacologic therapy of arrhythmias associated with the Wolff– Parkinson– White syndrome. See Also (Topic, Algorithm, Electronic Media Element)

• Atrial fibrillation • 12-lead EKG • Tachycardia

CODES ICD9 426.7 Anomalous atrioventricular excitation ICD10 I45.6 Pre-excitation syndrome

CLINICAL PEARLS

• Patients present perioperatively for ablative procedures or for unrelated surgical procedures. Anaesthetists need to optimize medical therapy, avoid sympathetic stimulation and make preparations to treat pre-excitation syndromes in patients with a diagnosis of WPW. In addition, the anaesthetist may play a role in initial diagnosis from a screening 12-lead EKG. • Amiodarone appears to be relatively safe in the acute management of both orthodromic and antidromic SVT, as well as in atrial fibrillation associated with WPW.

WORK OF BREATHING Thomas Verbeek, MBChB Revati Kanekar, MD

BASICS DESCRIPTION

• Work of breathing (WOB) is defined as the energy required for breathing movements. It is the cumulative product of the instantaneous pressure developed by the respiratory muscles and the volume of air moved during a breathing cycle. • WOB overcomes two main sources of impedance: Elastic and frictional. – Elastic work: Lung elastic recoil, thoracic cage displacement, and abdominal organ displacement (1)[C]. – Frictional (resistive) work: Airflow resistance (major component) and viscous resistance such as lobe friction (minor component). • The WOB depends upon the mode of breathing: – Spontaneous breathing: Performed by respiratory muscles (diaphragm, intercostals, accessory muscles, abdominal muscles) – Controlled ventilation: Performed by the ventilator – Assisted ventilation: Mostly performed by the ventilator. The initiation of spontaneous assisted breaths and dyssynchrony between spontaneous and assisted breaths are performed by the respiratory muscles. PHYSIOLOGY PRINCIPLES

• During quiet spontaneous breathing, expiration is passive and the WOB is performed entirely by the inspiratory muscles. Half of this work is dissipated as heat during inspiration (overcomes the opposing frictional forces). The other half is stored as potential energy in the deformed elastic tissues of the lungs and chest wall; it is available as a source of energy for expiration and then dissipated as heat to overcome frictional forces resisting expiration. Thus, because stored potential energy permits the work of inspiration to be transferred to expiratory muscles, the overall work performed is very small in healthy resting subjects (2) [C]. • Elasticity of pulmonary components: – Intrinsic elasticity of fibers is determined by collagen and elastin. They are decreased with aging and emphysema. – Surfactant decreases surface tension and elastic recoil (consequently decreases in surfactant result in increased surface tension and elastic recoil with consequent increase in WOB). • Elasticity of thoracic components: The elasticity of the chest wall (tendency to recoil outward) actually assists the inflation of the lungs; conversely, it opposes exhalation. • Functional residual capacity (FRC): At ∼35% of the vital capacity (VC), the recoil pressure of the lung and chest wall are equal, but opposite, resulting in an equilibrium volume

known as the functional residual capacity (FRC). Elastic work is required to expand or deflate the lungs from FRC. • Lung volume – Increases in volume (e.g., IRV, TLC): Airway resistance decreases (“pulled” open) Lung recoil increases Chest wall recoil decreases – Decreases in volume (e.g., ERV) Airway resistance increases Lung recoil decreases Chest wall recoil increases • Bronchial smooth muscle: Tone affects airway resistance; radius to the fourth power (r4) is inversely proportional to resistance. • Gas density and viscosity: Decreased density decreases turbulent flow; hence helium with a lower density than oxygen is utilized in certain scenarios. • Respiratory rate (RR): Increases in RR increase the WOB due to increased airflow. • Imposed WOB apparatus refers to equipment such as the endotracheal tube, breathing circuit, and ventilator. When breathing through a high-resistance apparatus at a high peak inspiratory flow rate, imposed work may exceed physiologic WOB. This can easily occur in pediatric patients because of the narrow internal diameter of an endotracheal tube (1)[C].

ANATOMY

• Rib cage: Contains and protects the lungs. The apex of the chest is small and widens at the base; the base is formed by the diaphragm. Parietal pleura is attached to the inside of the ribs and visceral pleura to the outside of the lungs. The intrapleural space is a potential space between these layers; it has a negative pressure that “pulls" them together and allows for coordinate and synchronous movement of the lungs and chest wall throughout the breathing cycle. • Diaphragm: Contraction of this principal pulmonary muscle causes the base of the thoracic cavity to descend 1.5–7 cm, and the lungs to expand outward. Diaphragmatic movement normally accounts for a 75% change in chest volume. Conditions that hinder diaphragmatic movement result in decreased muscle efficiency. Decreased contraction, and possible dyssynchrony; result in increased WOB. • Intercostal muscles increase chest volume by their action on the ribs. Upward and outward rib movements expand the chest. • Accessory muscles (sternocleidomastoid, scalene, pectoralis): During normal breathing, the diaphragm, and to a lesser extent, external intercostal muscles are responsible for inspiration. With increasing effort, the accessory muscles are recruited. • Abdominal muscles: Expiration is normally passive in the supine position but becomes active and facilitated by abdominal muscles in the upright position and with increased effort. They aid with downward movement of the ribs (3)[B].

DISEASE/PATHOPHYSIOLOGY

• Conditions that increase the WOB: – Certain skeletal deformities

– Respiratory disease – Pregnancy – Anemia • Increased WOB leads to: – Increased oxygen consumption up to 30% of total body VO2

– Respiratory muscle fatigue – Hypercapnia – Respiratory failure – These abnormalities are poorly tolerated in patients with pulmonary disease • Obstructive pulmonary diseases such as asthma and emphysema increase the work of breathing despite increased lung compliance. – Inspiration: Elastic work is decreased – Exhalation: Ventilatory muscles are used to actively exhale – Pulmonary mechanics: Increased FRC and gas trapping – Air flow: Velocity increases with turbulent flow; this, in turn, increases frictional forces – Compensation: FRC is increased to prevent dynamic airway collapse. However, these changes increase the WOB. • Restrictive pulmonary disease results from decreased lung (acute respiratory distress syndrome, pulmonary edema, fibrosis) or chest wall (severe chest wall injuries, kyphoscoliosis, obesity) compliance – Inspiration: Elastic work is increased; tidal volumes are decreased for a given change in intrapleural pressure – Exhalation: Smaller lung volumes result in decreased work – Pulmonary mechanics: Patients breathe at a lower FRC to conserve energy (increased effort is required to expand the lungs) – Compensation: Respiratory rate is increased to maintain minute ventilation. Spontaneous respiratory rate is one of the most sensitive indices of lung compliance.

PERIOPERATIVE RELEVANCE

• Although it is not commonly performed, measuring the WOB can aid with: – Assessing afterload on respiratory muscles – Ensuring patient–ventilator synchrony – Aiding weaning – Comparing different modes of ventilation • Methods to measure WOB – Esophageal pressures: Both compliance and inspiratory elastic work can be measured for a single breath by measuring airway pressure, intrapleural pressure, and tidal volume. Measurements are made in the mid-esophagus and can be used as a reflection of intrapleural pressure (4). Commercially available esophageal pressure monitors increase the ease and accuracy of measuring esophageal pressure. These monitors are useful for estimating the elastic work performed by the patient during spontaneous ventilation, mechanical ventilation, or a combination. By estimating intrapleural pressure on a real time basis, it is possible to quantitate the patient’s WOB and changes secondary to intervention.

– Computerized monitors with appropriate software and hardware differentiate the WOB and compliance components at the bedside CP 100, Bicore, Irvine California. • Decreasing the WOB – Continuous positive airway pressure (CPAP) can be used to treat increases in elastic work secondary to decreased lung compliance. With appropriate levels of CPAP, FRC increases, lung compliance improves, and elastic work decreases. – Pressure support ventilation (PSV) is a ventilator mode suited to reduce the imposed WOB and to partially or mostly unload the respiratory muscles (1)[C]. It may be useful in patients with decreased chest wall compliance. – Bronchodilator therapy may be appropriate in increased bronchial tone (increased airway resistance leads to increases in flow resistive work). – Low-resistance breathing system: Increases in imposed work from a high-resistance or faulty ventilator demand flow system are corrected by using a low-resistance breathing system. An endotracheal tube with a large internal diameter should be used when ventilatory support is anticipated during spontaneous ventilation with CPAP.

EQUATIONS

• Units of work – Joule is defined as the work done when a force of 1 N moves its point of application by 1 m. – It is also the work done when 1 L of gas moves in response to a pressure gradient of 1 kPa. 1 J = 1 Nm = 1 L kPa Power = work/time (W or J/sec) Work = Force × Distance – WOB = Pressure × Volume – VO2 (respiratory muscles) = 3 mL/min, <5% of total VO2, or <2% metabolic rate • The WOB is measured using the pressure–volume curve. This measurement requires placement of an esophageal balloon and either measurement of the chest wall compliance or the use of estimated (normal) chest wall compliance (5)[B]. – WOB = (PEE – POES) ∙ δV + 2 ∙ CCW/Vt 4(A), where PEE = end expiratory esophageal plateau pressure; POES = esophageal pressure at initiation of inspiratory flow; δV =

averaged flow rate; CCW = chest wall compliance; and Vt = tidal volume

REFERENCES

1. anner MJ, Jaeger MJ, Kirby RR. Components of work of breathing and implications for monitoring ventilator-dependent patients. Crit Care Med. 1994;22(3):515–523. 2. Update in Anesthesia. Respiratory Physiology Issue 12 (2000) article 11. Available from http://www.nda.ox.ac.uk/wfsa/html/pages/upissu.htm. 3. arrett J, Cerny F, Hirsch A. Control of breathing patterns and abdominal muscles during graded loads and tilt. J Appl Physiol. 1994;76(6):2473–2480. 4. Ballantine TVN, Proctor HJ. The work of breathing. Ann Surg. 1970;171(4):590–595. 5. Cabello B, Mancebo J. Work of breathing. Intensive Care Med. 2006;32:1311–1314.

6. Weavind L, Shaw AD. Monitoring ventilator weaning-predictors of success. J Clin Monit Comput. 2000;16:409–416.

ADDITIONAL READING

• Branson R. Respiratory Care 2000. Monitoring Work of Breathing. 2000 Open Forum Abstracts. Available from http://www.rcjournal.com/abstracts/2000/?id=A00000400 • Charles W. Mechanics of Breathing. Loyola University Medical Education Networking. Available from http://www.meddean.luc.edu/lumen/MedEd/medicine/pulmonar/physio/menu_f.htm See Also (Topic, Algorithm, Electronic Media Element) • Respiratory system compliance • Functional residual capacity • Continuous positive airway pressure

CLINICAL PEARLS

• Work of breathing involves two major components—elastic work and frictional work. • The normal value for WOB is 0.5 J/L of ventilation in normal adults (range: 0.3–0.6 J/L). • During spontaneous ventilation, the majority of work is done during inspiration; expiration is largely passive. • Patients with obstructive pulmonary pathology breathe at high tidal volumes to minimize the work of breathing. Patients with restrictive lung disease have a rapid shallow respiration to conserve energy. • Measuring WOB helps in weaning a patient from ventilator support and it is also used as a research tool to compare different modes of ventilation. • Surrogates for the WOB include simple measurements such as the frequency/tidal volume ratio and respiratory rate (3)[C].

AMIDE LOCAL ANESTHETICS Joseph Koveleskie, MD

TREATMENT DRUGS

Articaine (Septocaine®, Zorcaine®, Articadent®) • Usual dose – Adult/children age >4: Maximum recommended dose 7 mg/kg – Pregnancy risk C – Breastfeeding unknown, use caution Mechanism of Action

Reversible sodium channel blockade, inhibiting action potential formation and conduction in nerve fibers Uses

• Local, infiltrative, or conductive anesthesia in both simple and complex dental and periodontal procedures • Has also been used for peripheral nerve blocks, epidural, spinal, and intravenous regional anesthesia (IVRA) (Bier block) Onset Fast

Duration

60 minutes

Metabolism

Plasma/hepatic carboxylesterase to inactive metabolite, excreted in urine Adverse Effects

• As is typical for all local anesthetics after intravascular injection or high plasma levels from absorption of large dose: CNS excitation/depression, seizure, respiratory arrest, dysrhythmias, hypotension, and death. Rate of systemic absorption and toxicity is determine by tissue blood flow: Intravenous > tracheal > intercostals > caudal > paracervical > epidural > brachial plexus > sciatic > subcutaneous • Allergic reactions to amides (skin or anaphylactoid reactions) are possible but extremely rare. Most reactions are to preservative additives or are epinephrine-related • May cause methemoglobinemia

CLINICAL PEARLS

• Commonly used in Europe and elsewhere, approved in the US in 2000, mostly combined with epinephrine for dental use • Claimed to be less toxic than lidocaine, attributed mainly to rapid hydrolysis to an inactive metabolite • Consider lipid emulsion rescue therapy for intravascular injection of all local anesthetics

TREATMENT DRUGS

Bupivacaine (Marcaine®, Sensorcaine®, Vivacaine®) • Toxicity: 2.5 mg/kg • Pregnancy risk C • Breastfeeding not recommended, enters breast milk

Mechanism of Action

• Reversibly blocks the fast voltage gated sodium channels on central and peripheral nerves and cardiac pacemaker cells, thus interfering with the conduction of action potentials. They do not change or alter the membrane resting potential • Weak bases. Exist as powdered solids that are unstable in air and poorly soluble in water. Need to be combined with hydrochloric acid to form an ionized molecule that is water soluble • Site of action is intracellular; thus, the unprotonated, non-ionized form is required to cross the lipid bilayer and gain access to the receptor site (onset is thus dependent on its pKa). When pH = pKa, 50% of drug is uncharged and 50% is charged • Potency is mainly determined by lipid solubility; longer hydrocarbon chains can cross the lipid bilayer readily • Duration of action is determined by protein binding (alpha-1 glycoprotein); local anesthetics are only active in their free, unbound form. Pathologic states (malnourishment, liver disease) increase the amount of free drug (doses should be decreased)

Uses

Widely and extensively used for broad range of local/regional anesthetic techniques, although extreme caution is warranted to guard against intravascular injection or exceeding recommended maximum dose Onset

Infiltration and spinal—fast, epidural—moderate, peripheral nerve block—slow Duration

Spinal 60–240 minutes, infiltration 120–480 minutes, epidural 120–300 minutes, peripheral nerve block 240–960 minutes Metabolism

Hepatic microsomal enzymes, metabolites excreted in urine. Compared to the rapid

metabolism of esteratic local anesthetics, amide local anesthetic metabolism is slower and more complex. Sustained increase in plasma concentration and systemic toxicity probably more likely with amides compared to esters Adverse Effects

• Systemic toxicity, as described in “Articaine” • At high plasma levels, can cause dysrhythmias and asystole that are particularly difficult or impossible to treat with traditional ACLS or supportive measures alone • Allergic reactions to amides are possible but extremely rare. Most true “allergic” reactions are to preservative additives. Chondrolysis may occur if used in intra-articular infusion

CLINICAL PEARLS

• Avidly binds to cardiac sodium channels and dissociates very slowly, making resuscitation prolonged and difficult. An often-stated maxim for using local anesthetics, bupivacaine in particular, is to “treat every dose as a test dose.” Cardiac toxicity can be aggravated by betablockers, digitalis, calcium channel blockers, epinephrine, phenylephrine, hypoxemia, hyperkalemia, acidosis, and hypercarbia. Consider lipid emulsion early • Not recommended for IVRA

TREATMENT DRUGS

Dibucaine aka Cinchocaine (Nupercainal®, Nupercaine®, Rectacaine®) Mechanism of Action

Reversible sodium channel blockade, see “Articaine” Uses

Topical cream and suppositories for pain, pruritus, and inflammation of minor skin disorders, particularly hemorrhoids in OTC preparations. Also used in the laboratory to test inhibition of pseudocholinesterase activity Onset Fast

Duration

3–4 hours

Metabolism

Metabolized in the liver, and is the most slowly eliminated amide. Has been used for spinal anesthesia in other countries, banned in the US for spinal use due to toxicity Adverse Effects

Similar to others in the amide class. Also contact dermatitis, immune hypersensitivity

reaction, and photosensitivity

CLINICAL PEARLS

Consider lipid emulsion rescue therapy for intravascular injection of all local anesthetics

TREATMENT DRUGS

Etidocaine (Duranest®)

Usual dose: Maximum 300 mg, 400 mg with epinephrine Mechanism of Action

Reversible sodium channel blockade, see “Articaine” Uses

• Epidural, dental, and ophthalmologic infiltration • Also used as topical for intubation and postoperative analgesia in tubal ligation surgery, and for peripheral nerve block Onset Fast

Duration

Infiltration and epidural 120–480 minutes, peripheral nerve block 180–720 minutes Metabolism

Similar to other amides, but slower. <1% excreted unchanged in urine Adverse Effects

Similar to others in the amide class

CLINICAL PEARLS

• Removed from US market in 2001 • Causes considerably more pain on injection than other local anesthetics • Strong motor block but may not provide adequate sensory block for epidural • Causes porphyria in animals

TREATMENT DRUGS

Lidocaine (Xylocaine®, EMLA®) • Toxicity: 5 mg/kg, with epinephrine 7 mg/kg

• Pregnancy risk B • Breastfeeding caution

Mechanism of Action

Reversible sodium channel blockade, see “Bupivacaine” Uses

• Topical, infiltration or regional anesthesia, including caudal, epidural, and spinal blocks • Ventricular dysrhythmias, used in ACLS/PALS • Attenuation of sympathetic response and blunting of laryngeal reflexes during airway manipulation (laryngoscopy, intubation, suctioning) • Contributes to MAC (reduced MAC and propofol dosing needed) • Reduces pain/discomfort associated with propofol injection • Combined with prilocaine in EMLA cream, a topical product

Onset Fast

Duration

Topical, IVRA, and spinal 30–60 minutes, epidural 60–120 minutes, peripheral nerve block 60–180 minutes, infiltration 60–240 minutes Metabolism

Hepatic, to active metabolites (which can accumulate and contribute to toxicity), excreted in urine Adverse Effects

Similar to others in the amide class. May rarely cause methemoglobinemia

CLINICAL PEARLS

• Most commonly used drug for Bier block • Transient neurologic symptoms [TNS] have been reported with spinal anesthesia (doses as low as 0.5%). Cauda equina syndrome is associated with maldistribution or nonhomogenous distribution (microcatheters <28 g) • Sodium bicarbonate (1–2 cc of 8.4% NaHCO3 with 18–19 cc lidocaine) may be added to

increase the % of drug that is uncharged and can cross the bilipid cell membrane, shorten the onset of blockade, enhance the depth of sensory and motor blockade, and increase the spread of epidural blockade

TREATMENT DRUGS

Mepivacaine (Carbocaine®, Isocaine®, Polocaine®, Scandonest®) • Toxicity: 5 mg/kg, with epinephrine 7 mg/kg

• Pregnancy risk C • Breastfeeding unknown, use caution

Mechanism of Action

Reversible sodium channel blockade, see “Bupivacaine” Uses

Epidural, peripheral nerve block, infiltration Onset Fast

Duration

Spinal 60–120 minutes, epidural 60–180 minutes, infiltration 60–240 minutes, peripheral nerve block 120–240 minutes Metabolism

Hepatic, metabolites substantially excreted renally. Decreased clearance in neonates leading to prolonged elimination half time Adverse Effects

Similar to others in the amide class

CLINICAL PEARLS

• Causes less vasodilation and so can be used without epinephrine for similar effect • May be used in a Bier block

TREATMENT DRUGS

Prilocaine (Citanest®, EMLA®) • Toxicity: 8 mg/kg • Pregnancy risk B • No known issues with breastfeeding

Mechanism of Action

Reversible sodium channel blockade, see “Bupivacaine” Uses

Infiltration, peripheral nerve block, Bier block, topical (combined with lidocaine) Onset Fast

Duration

IVRA 30–60 minutes, infiltration 60–120 minutes, epidural 60–180 minutes, peripheral nerve block 90–180 minutes Metabolism

Hepatic and renal, most rapidly metabolized of amides. Metabolites excreted by kidney. Metabolite O-toluidine may produce methemoglobin Adverse Effects

Metabolite o-toluidine converts hemoglobin to methemoglobin (cannot bind O2 or CO2),

resulting in the loss of hemoglobin’s transport function

CLINICAL PEARLS

• Causes less vasodilation than other drugs (can be utilized without epinephrine) • May be used as alternative to lidocaine for a Bier block • Combined with lidocaine in a eutectic mixture as a cream (EMLA®), for topical anesthesia • Patients taking drugs associated with drug-induced methemoglobinemia (sulfonamides, acetaminophen, acetanilid, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, paraaminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, and quinine) are also at greater risk for developing methemoglobinemia

TREATMENT DRUGS

Ropivacaine (Naropin®)

• Toxicity 3 mg/kg • Pregnancy risk B • Breastfeeding unknown, caution advised

Mechanism of Action

Reversible sodium channel blockade, see “Bupivacaine” Uses

Epidural and peripheral nerve block, spinal Onset

Infiltration—fast, epidural—moderate, peripheral nerve block—slow Duration

Infiltration and epidural 120–360 minutes, peripheral nerve block 300–480 minutes Metabolism

Hepatic/extensive via CYP1A2, metabolites excreted in urine. In uremic patients a toxic metabolite may accumulate

Adverse Effects

Similar to others in the amide class

CLINICAL PEARLS

• Gained popularity due to greater differential blockade (sensory > motor) and decreased cardiotoxicity compared to bupivacaine • Has been used in Bier blocks but is not recommended • Intrinsic vasoconstrictor activity precludes the need for epinephrine

ANGIOTENSIN CONVERTING ENZYME INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Angiotensin converting enzyme inhibitors (ACEIs) • Dose reduction required for renal dysfunction, and slow titration/reduction in dose required in elderly patients • Pregnancy: C first trimester, D second, and third • Breastfeeding not recommended

Mechanism of Action

• Impairs conversion of angiotensin-I to angiotensin-II, which normally increases aldosterone release by the adrenal cortex and acts as a renal arteriolar constrictor • Also impairs breakdown of bradykinin, a vasodilator Table 1 Angiotensin converting enzyme inhibitors Uses

• Chronic or acute hypertension • Hypertensive crisis • Congestive heart failure • Post myocardial infarction • Renal protection in diabetics or those with preexisting renal disease

Adverse Effects

Cough, taste alteration, hypotension, headache, dizziness, fatigue, exacerbation of renal failure in patients with renal artery stenosis or in hypovolemic patients, increase in serum creatinine, hyperkalemia, angioedema (more common in black populations and females), rash

CLINICAL PEARLS

• Perioperative use is controversial; intraoperative hypotension is common when administered preoperatively to patients receiving general anesthesia, but postoperative hypertension and atrial fibrillation are more common if not given. Vasopressin may be required to treat refractory intraoperative hypotension • Contraindicated in pregnancy due to a risk of fetal demise/malformations • NSAID’s antagonize hypotensive effects of ACEIs and increase the risk of renal dysfunction. Control of BP should be monitored if used concurrently • Angiotensin receptor blockers may be used as an alternative in patients with ACE-I induced cough or angioedema

• Often combined with diuretic agents • Hyperkalemia more common in patients taking potassium supplementation or other drugs that cause hyperkalemia

TREATMENT DRUGS

Angiotensin receptor blockers (ARBs) • Pregnancy category: C first trimester, D second, third trimester • Breastfeeding not recommended

Mechanism of Action

• Antagonizes effects of angiotensin II at angiotensin receptors • Inhibits vasoconstriction and aldosterone secretion • Does not impair the degradation of bradykinin

Uses

• Chronic hypertension • Congestive heart failure • Renal protection in diabetics or those at risk for renal disease

Adverse Effects

Hypotension, headache, dizziness, alteration of taste, diarrhea, sexual dysfunction, hyperkalemia, increase in serum creatinine, renal dysfunction

CLINICAL PEARLS

• Same perioperative concerns as ACEIs • Alternative agents for patients intolerant to ACEI. Cough and angioedema are possible but relatively rare compared to ACEIs • Must be avoided in pregnancy due to risk of fetal death/malformations • Commonly combined with diuretic agent • Hyperkalemia more common in patients who are taking potassium supplementation or other drugs that cause hyperkalemia • No IV forms available • Duration of action tends to be longer than ACEIs • NSAIDs decrease the efficacy of ARBs and increase the risk of renal dysfunction Table 2 Angiotensin receptor blockers

ANTIARRHYTHMIC AGENTS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Adenosine (Adenocard®) • IV: for SVT 6 mg rapid bolus, may repeat 12 mg doses every 1–2 minutes • Pediatric (PALS doses) 0.1 mg/kg up to 6 mg, may repeat at 0.2 mg/kg up to 12 mg • Pregnancy risk C • Lactation unknown

Mechanism of Action

Slows conduction through the AV node via inhibition of calcium channels; smooth muscle relaxation in the vasculature Uses

• Paroxysmal supraventricular tachycardia • ACLS tachycardia protocols • Pharmacologic stress tests

Onset

Rapid/seconds Duration

Half-life 10 seconds Metabolism

Rapidly metabolized to AMP and hypoxanthine in blood and tissue; excreted renally as uric acid Adverse Effects

Transient conduction blocks—1st, 2nd, 3rd degrees, new transient dysrhythmias, flushing, palpitations, chest pain, hypotension, dyspnea, bronchoconstriction, headache, dizziness, diaphoresis

CLINICAL PEARLS

• Contraindicated in patients with 2nd or 3rd-degree heart blocks, sick sinus syndrome, symptomatic bradycardia (unless patient has a functioning pacemaker) • Ventricular tachycardia may result in patients with WPW • Theophylline and caffeine antagonize action of adenosine • Prolonged effects occur in patients on carbamazepine or dipyridamole, or with

transplanted/denervated hearts

Table 1 Class IA antiarrhythmics

TREATMENT DRUGS

Digoxin (Lanoxin®) • IV for ventricular rate control: 0.5–1.0 mg total digitalizing dose, one half given initially, then one fourth given every 6 hours • PO for ventricular rate control: 0.75–1.5 mg initial dose, maintenance 0.125–0.5 mg PO QD • PO CHF: 0.125–0.25 mg QD • Doses require adjustment for renal insufficiency • Pediatric doses vary by age, weight, and indication • Pregnancy risk C • Enters breast milk, caution advised with breastfeeding

Mechanism of Action

• Suppresses conduction at the AV node directly as well as via increased vagal tone • Increases contractility via blockade of Na+/K+ exchange pump, which facilitates Ca2+ influx

Uses

• Heart rate control in patients with atrial fibrillation or flutter with rapid ventricular rates • Mild or moderate CHF

Onset

IV 5–60 minutes, PO 1–2 hours Duration 3–4 days

Metabolism

• PO form metabolized in gut to some extent • Once absorbed, some metabolism occurs (50–70% excreted unchanged in the urine); some metabolites are active and contribute to toxicity Adverse Effects

Proarrhythmia (especially if toxicity exists), dysrhythmias with or without heart blocks, dizziness, weakness, confusion, delirium, nausea, vomiting, visual disturbances

CLINICAL PEARLS

• Specific antagonist exists to reverse toxicity (Digibind Fab) • Hypokalemia and hypomagnesemia increase risk of toxicity, and should be corrected prior to or during therapy

• Increases ventricular rates with WPW/bypass tracts • Has many drug interactions • Serum levels need close monitoring, especially if patient is at risk for changing renal function, electrolyte disturbances, or if alteration in drug therapy occurs

TREATMENT DRUGS

Class IA antiarrhythmics—quinidine,procainamide, disopyramide

Mechanism of Action

• Blocks fast sodium channels, slows phase 0 depolarization, decreases conduction velocity, and increases action potential duration/effective refractory period • Varying anticholinergic effects

Uses

• Atrial fibrillation/flutter • SVT • Suppression of ventricular dysrhythmias • IV procainamide for life-threatening VT/VF, treatment of WPW syndrome • Quinidine may be used to treat severe malaria

Adverse Effects

Proarrhythmia, prolongs QT interval/increases risk of Torsade, tachycardia, dry mouth, urinary retention, constipation, potentiation of volatile anesthetic-induced cardiac depression. Quinidine—hypotension, thrombocytopenia, cinchonism, diarrhea, fever, rash, hepatitis. Procainamide decreases contractility, hypotension, blood dyscrasias, drug-induced lupus, fever, rash. Disopyramide decreases contractility, hypoglycemia

CLINICAL PEARLS

• Only used occasionally due to frequent toxicity

TREATMENT DRUGS

Class IB antiarrhythmic agent (mexiletine) • PO 200–300 mg every 8 hours, dose should be decreased in patients with hepatic dysfunction or CHF • Pregnancy risk C • Enters breast milk, compatible with breastfeeding

Mechanism of Action

Blocks fast sodium channels and decreases action potential duration/effective refractory

period Uses

• Life-threatening ventricular dysrhythmias • Refractory or chronic neuropathic pain syndromes

Onset

Time to peak 2–3 hours Duration

Half life 10–14 hours Metabolism

Hepatic via CYP1A2, to inactive metabolites; small amount excreted unchanged in urine Adverse Effects

Proarrhythmia, hypotension, tachy/bradycardia, LV dysfunction/worsening CHF, dizziness, tremor, GI side effects, ataxia, lightheadedness, hypersensitivity syndrome. Considered to be oral lidocaine analog.

CLINICAL PEARLS

• Volatile anesthetics may worsen cardiac depressant effects • Potent CYP1A2 inhibitor and has several drug interactions (theophylline, SSRIs)

TREATMENT DRUGS

Class IC antiarrhythmic agents (propafenone, flecainide)

Mechanism of Action

• Blockade of sodium channels with a decrease in phase 0 depolarization velocity, but does not affect action potential duration or effective refractory period, decreases conduction velocity • Propafenone has some beta-blocking activity and calcium channel blockade effects at high doses Uses

• Atrial fibrillation and SVT, including WPW • Life-threatening ventricular dysrhythmias

Adverse Effects

• Proarrhythmic effects (more common in patients with ischemia/structural heart disease), prolongation of QT interval, hypotension, decreased contractility, worsening CHF, bradycardia, nausea, vomiting, anorexia, headache, dizziness, visual disturbances

• Flecainide—palpitations, chest pain, dyspnea • Propafenone—lupus-like syndrome, blood dyscrasias, bronchospasm, altered taste

CLINICAL PEARLS

• Cardiac depressive effects augmented by anesthetics • “Pill in the pocket" approach for control of paroxysmal atrial fibrillation in certain patients —unlabeled use • Hypokalemia and hypomagnesia should be avoided • Many drug interactions—both are substrates of CYP2D6

TREATMENT DRUGS

Class III agents Amiodarone (Cordarone®) • IV for VT/VF ACLS: 300 mg, then 150 mg if dysrhythmia unresponsive or recurs • PO maintenance for ventricular dysrhythmias 400 mg/day. Smaller doses used in atrial dysrhythmias. May need dose reduction in patients with severe hepatic disease • Pediatric (PALS) 5 mg/kg IV, up to 15 mg/kg/day • Pregnancy risk D • Breastfeeding not recommended

Mechanism of Action

• Impairs sodium channel conductance, suppresses sinus and AV node, blocks outward potassium channels/prolongs action potential duration and effective refractory period, inhibits calcium flux and decreases contractility • Some peripheral vasodilation

Uses

Life-threatening VT, ventricular fibrillation, ACLS, atrial fibrillation/flutter, SVT Onset

Oral 2 days to 3 weeks, IV more rapid. Peak effect 1 week to 5 months Duration

May last 7–50 days after discontinuation Metabolism

Hepatic, via CYP2C8 and 3A4 to active metabolite, excreted fecally Adverse Effects

Proarrhythmia, prolongation of QT interval and Torsade, bradycardia, decreased contractility, hypotension, pulmonary fibrosis, chronic interstitial pneumonitis, ARDS, lung masses, pleuritic chest pain, ataxia, dizziness, hyper or hypothyroidism, optic neuropathy/blindness,

corneal deposits, photosensitivity, phlebitis, hepatotoxicity

CLINICAL PEARLS

• Considered to be less proarrhythmic than other agents • Cardiac depression augmented by anesthetic agents. Has less effect on contractility than other agents so is preferred in patients with LV dysfunction • Large iodine load released upon metabolism

TREATMENT DRUGS

Sotalol (Betapace®) • IV 1.5 mg/kg over 5 minutes (ACLS) • PO initial 80 mg BID, up to 320 mg/day. Doses must be adjusted in renal insufficiency or excessive prolongation of QT interval • Pediatric (age >2 years): 90 mg/m2/day in 3 divided doses, up to 180 mg/m2 /day • Pregnancy risk B • Enters breast milk

Mechanism of Action

• Impairs conductance at potassium channels and prolongs action potential duration and repolarization • Has nonspecific beta-blocking activity

Uses

• Treatment/prevention of VT and VF, atrial fibrillation/flutter • IV form indicated for monomorphic, hemodynamically stable VT

Onset

1–2 hours Duration

8–16 hours

Metabolism

Excreted unchanged by kidney Adverse Effects

Proarrhythmia, QT prolongation and Torsade, bradycardia, worsening CHF, bronchospasm, fatigue, dyspnea, dizziness

CLINICAL PEARLS

Has same concerns/adverse effects as beta-blockers, including withdrawal phenomena, avoid

sudden discontinuation of drug. Additive cardiac depression with anesthetic agents Table 2 Class IC antiarrhythmic agents

ANTIBIOTICS

Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Vancomycin (Vancocin®) • Usual dose is based on actual body weight (approximately 12–15 mg/kg): 50–65 kg 750 mg IV, 66–82 kg 1000 mg IV, 83–99 kg 1250 mg IV, >100 kg 1500 mg IV over 1–2 hours. Subsequent doses may be given every 12–24 hours; adjustments need to be made to dosing interval for impaired renal function • Pediatric dosing 20 mg/kg IV; subsequent doses every 6 hours • Pregnancy risk C • Breastfeeding not recommended/enters breast milk

Mechanism of Action

Glycoprotein antibiotic, bacteriocidal, inhibits cell wall synthesis in Gram-positive bacteria by blocking glycopeptide polymerization Uses

• Perioperative antibiotic prophylaxis in neurosurgery and orthopedic surgery • Infections due to susceptible organisms—Staphylococci (including methicillin-resistant S. aureus [MRSA], Streptococci, Enterococci

Onset

IV: Time to peak immediately at end of infusion Duration

Half life 5–12 hours, highly dependent on renal function Metabolism

80–90% excreted unchanged via kidney Adverse Effects

Nephrotoxicity, ototoxicity, “red man syndrome”—flushing, hypotension, tachycardia, transient rash/hives, pruritus, chills

CLINICAL PEARLS

• Red man syndrome is not a true allergy. It is due to non-immunogenic histamine release and is related to rapid infusion; it can be decreased with slow infusion and/or antihistamines • May be used for preoperative surgical prophylaxis in patients with true allergies to penicillins or cephalosporins

• Trough levels should be 15–20 mcg/mL • Additive nephrotoxicity may be seen with aminoglycosides/other nephrotoxins • Extravasation may cause severe tissue injury

TREATMENT DRUGS

Linezolid (Zyvox®) • Usual dose: IV/PO 600 mg every 12 hours • Pediatric (age <12) 10 mg/kg, up to IV/PO 600 mg, every 8 hours. No adjustments required for renal/hepatic dysfunction • Pregnancy risk C • Breastfeeding unknown

Mechanism of Action

• Inhibits bacterial protein synthesis by binding to 50S ribosomal subunit • Bacteriostatic against Enterococci and Staphylococci, bacteriocidal against Streptococci

Uses

VRE, MRSA infections, pneumonia, skin structure infections, osteomyelitis caused by susceptible organisms Onset

Time to peak: 1–2 hours with PO dosing, IV at end of infusion Duration

Half life 4–5 hours Metabolism

Predominately hepatic oxidation to inactive metabolites (65%), 30% renal as unchanged drug Adverse Effects

Headache, diarrhea, nausea, increased liver enzymes, lipase, amylase, thrombocytopenia

CLINICAL PEARLS

• Has MAO-inhibiting activity, increases risk of serotonin syndrome when given with other agents that predispose to serotonin syndrome. Same dietary and drug interaction precautions as MAO inhibitors • Exhibits time-dependent kill characteristics • Bone marrow suppression may occur, especially with prolonged use

TREATMENT DRUGS

Metronidazole (Flagyl®)

• Usual dose: 500 mg IV every 8 hours, may give 1000 mg IV loading dose; should be given within 1 hour of incision. Repeat dosing of 500 mg IV can be given at 6 and 12 hours after incision • Pediatric dosing 30 mg/kg/day given every 8 hours • Doses need to be reduced 50% for severe hepatic or renal disease • Pregnancy risk B • Breastfeeding not recommended/enters breast milk

Mechanism of Action

Bacteriocidal, causes loss of helical DNA structure and strand breakage, resulting in decreased protein synthesis in susceptible bacteria Uses

• Prophylaxis for colorectal surgery, or where anaerobic/enteric pathogens are a consideration • Treatment of certain anaerobic or protozoal infections

Onset

Time to peak: 1–2 hours with PO dosing Duration

Half life 6–8 hours, >20 hours in renal failure Metabolism

30–60% hepatic via CYP3A4, 2C6, to a somewhat active metabolite; metabolites are mostly excreted in the urine, some in bile/feces Adverse Effects

Dizziness, peripheral or optic neuropathy, nausea, flu-like symptoms, disulfiram-like reactions, rash, hypersensitivity reactions

CLINICAL PEARLS

Less frequently used for surgical prophylaxis as it is a moderate inhibitor of CYP3A4 (affects drug metabolism)

TREATMENT DRUGS

Clindamycin phosphate (Cleocin®) • Usual dose: 900 mg IV over 10–20 minutes, 30–60 minutes prior to procedure; may be repeated in 8 hours. Dose adjustments need to be made in hepatic disease, but not for renal disease • Pediatric dosing 20 mg/kg IV

Mechanism of Action

Bacteriostatic or bacteriocidal (dependent on target organism, infection site, drug concentration), binds to 50S ribosomal subunit and reversibly inhibits bacterial protein synthesis Uses

• Surgical prophylaxis in patients with risk of anaerobic infections, mostly as an alternative in patients truly allergic to penicillins or cephalosporins • Effective against Streptococcus, Staphylococcus, Pneumococcus Onset

Time to peak: 1 hour (if given PO or IM) Duration

Half life 2–3 hours Metabolism

Hepatic, to variably active metabolites Adverse Effects

Pruritus, rash, eosinophilia, agranulocytosis, neutropenia, jaundice, abnormal liver function tests, rare cardiac arrest/hypotension, abdominal pain, diarrhea, pseudomembranous colitis

CLINICAL PEARLS

• Usually combined with a fluoroquinolone or an aminoglycoside when used for prophylaxis • May enhance/prolong neuromuscular blockade produced by non-depolarizing neuromuscular blockers • Inducible resistance to clindamycin may occur

TREATMENT DRUGS

Aminoglycosides: Gentamicin (Garamycin®), Tobramycin (Nebcin®) • Usual dose: 1.5–2.0 mg/kg IV (may be given IM) based on ideal body weight; usually infused over 30 minutes. May be repeated every 8 hours. Doses and interval need to be adjusted in renal insufficiency and based on peak/trough levels • Pregnancy risk D • Breastfeeding not recommended/enters breast milk

Mechanism of Action

Bacteriocidal, irreversible binding to 30S and 50S ribosomal subunits in susceptible bacteria, causing inhibition of protein synthesis and defects in bacterial cell membranes Uses

• Surgical prophylaxis in GI or GU surgery • Infections caused by aerobic Gram negatives, including Pseudomonas, some Gram positives • Ineffective against anaerobes

Onset

Peak at end of 30-minute infusion Duration

Half life of 1.5–3 hours, progressively prolonged if renal function declines Metabolism

Excreted unchanged by kidneys Adverse Effects

Nephrotoxicity, ototoxicity (vestibular and/or auditory), muscle weakness

CLINICAL PEARLS

• May prolong/intensify neuromuscular blockade produced by non-depolarizing neuromuscular blockers • Exhibits concentration-dependent killing of micro organisms • Usually used in combination with a beta-lactam antibiotic to enhance efficacy • Ototoxicity may be worsened by diuretics. Peak and trough levels must be followed if used beyond immediate perioperative period, especially if renal function deteriorates. May cause hearing loss in fetus/newborn if given to mother during pregnancy • A nebulized version of tobramycin may be given via aerosol to cystic fibrosis patients infected with Pseudomonas aeruginosa

TREATMENT DRUGS

Fluoroquinolones: Ciprofloxacin (Cipro®), Levofloxacin (Levaquin®) • Ciprofloxacin 400 mg IV, may also be given PO; can be repeated every 8–12 hours, as indicated • Levofloxacin 500 mg IV every 24 hours. Should be administered over 1 hour. Doses need to be adjusted for renal dysfunction • Pregnancy risk C • Breastfeeding not recommended/enters breast milk

Mechanism of Action

Bacteriocidal, inhibits bacterial DNA gyrase and subsequent DNA uncoiling, promotes breakage of double-stranded DNA Uses

• Surgical prophylaxis in GU/prostate surgery

• In patients with a true beta-lactam allergy may be given concomitantly with clindamycin for head and neck, gastric, or biliary surgery • Infections due to enteric Gram-negative organisms; active against some Gram-positive cocci

Onset

Peak levels occur at the end of infusion Duration

Ciprofloxacin half life 3–5 hours, levofloxacin half life 6–8 hours Metabolism

• Ciprofloxacin is hepatically metabolized, to 4 partially active metabolites. 30–50% excreted in urine as unchanged drug. Potent CYP1A2 inhibitor • Levofloxacin is excreted unchanged (87%) in urine with little metabolism

Adverse Effects

Polyneuropathy, tendon rupture, QT prolongation/Torsades de Pointes, convulsions, dizziness, confusion, hypoglycemia, muscle weakness

CLINICAL PEARLS

• Caution when given to patients on other agents that prolong QT interval • Tendon rupture more common in patients on corticosteroids, anti-rejection agents, and those aged 60 and older • Should be avoided in myasthenia gravis (increases muscle weakness) • Should not be used in children unless multidrug-resistant pathogens show sensitivity to fluoroquinolones

TREATMENT DRUGS

Aztreonam (Azactam®) • Usual dose: 1–2 grams IV every 6–12 hours • Surgical prophylaxis dose 2 grams IV • Adjust for renal insufficiency • IM administration may also be performed • Pediatric dosing 30 mg/kg every 8 hours • Pregnancy risk B • Breastfeeding not recommended/enters breast milk

Mechanism of Action

Bacteriocidal, similar to beta-lactam, inhibits cell wall cross-linkage Uses

• Alternative surgical prophylaxis in penicillin-allergic patients for neurosurgery via

nasal/sinus approaches • Limited to use for Gram-negative infections

Onset

Time to peak: 60 minutes IV or IM Duration

Half life 2–3 hours, prolonged in renal failure Metabolism

Renal excretion 60–70% as unchanged drug, some hepatic metabolism Adverse Effects

Rash, nausea, vomiting, diarrhea

CLINICAL PEARLS

• Is a monobactam agent without cross-allergenicity to penicillins or cephalosporins • Increased risk of enterococcal superinfection and Clostridium difficile associated diarrhea/infection with prolonged use

TREATMENT DRUGS

Ertapenem (Invanz®) • Usual dose: 1 gram IV, infuse over 30 minutes (decrease to 500 mg if CrCl <30 mL/minute) • Can be given IM • Pediatric dosing (age <12 years) 15 mg/kg • Pregnancy risk B • Breastfeeding caution/enters breast milk

Mechanism of Action

Bacteriocidal, similar to other beta-lactams, inhibits bacterial cell wall synthesis, effective against Gram-positive, Gram-negative and anaerobic bacteria Uses

Surgical prophylaxis in patients having colorectal surgery or with ruptured viscus/peritoneal contamination Onset

Time to peak: (IM) 2–3 hours Duration

Half life 4 hours Metabolism

80% renal excretion of unchanged drug and inactive metabolite, non-CYP mediated hydrolysis Adverse Effects

Confusion, seizures, headache, nausea, diarrhea, liver enzyme elevations, thrombocytosis

CLINICAL PEARLS

May have cross-allergenicity with penicillins and/or cephalosporins. Potential for C. difficile pseudomembranous colitis

TREATMENT DRUGS

Penicillins: Penicillin G, Ampicillin/Sulbactam (Unasyn®) • Penicillin G 2 million units IV, repeat every 4–6 hours as needed. Pediatric dosing 100,000– 400,000 units/kg/day to be divided every 4–6 hours • Ampicillin/sulbactam 3 grams IV, over 15–30 minutes; may be repeated every 6 hours. Dose or interval after the first dose may need adjustment in patients with end-stage renal disease. Pediatric dosing 100–400 mg/kg/day divided every 6 hours • Pregnancy risk B • Breastfeeding caution/enters breast milk

Mechanism of Action

• Bacteriocidal, beta-lactam agents that inhibit cross-linking of peptidoglycan cell wall components • Penicillin G—a natural penicillin—is primarily active against Streptococcus, Pneumococcus, and Meningococcus, and anaerobes inhabiting the oral cavity • Ampicillin is a semisynthetic aminopenicillin that has activity against some Gram-negative aerobes. Sulbactam is an inhibitor of beta-lactamase

Uses

• Penicillin G still used for surgical prophylaxis for some oral procedures • Ampicillin/sulbactam used for surgical prophylaxis for head and neck, gastric–biliary, or GU surgery

Onset

Time to peak: 1 hour Duration

Penicillin half life 30–50 minutes, ampicillin 1–1.3 hours Metabolism

Renal filtration and tubular secretion of unchanged drug, hepatic metabolism to inactive metabolite (30%)

Adverse Effects

Fever, rash, hypersensitivity reactions, neurotoxicity/seizure with high doses, hyperkalemia or hypernatremia with high doses (especially in renal failure), nephritis, diarrhea

CLINICAL PEARLS

• Low incidence of true anaphylaxis, <6% risk of cross-allergenicity with cephalosporins. Delayed rash (48 hours after first dose) may not contraindicate use • Penicillins mostly supplanted by cephalosporins for perioperative prophylaxis • Unasyn 3 grams is equal to 2 grams ampicillin with 1 gram sulbactam • Potential for electrolyte disturbances due to sodium or potassium in the preparation

TREATMENT DRUGS

Cephalosporins: Cefazolin (Ancef®), Cefoxitin (Mefoxin®), Cefotetan • Usual dose: 1–2 grams IV over 5–30 minutes. Surgical prophylactic doses should be given 30–60 minutes prior to the procedure and repeated every 3–4 hours for prolonged procedures. Doses and intervals may need to be adjusted in patients with renal failure • Pediatric dosing: Cefazolin 50 mg/kg, cefoxitin 30–40 mg/kg, cefotetan 40 mg/kg • Pregnancy risk B • Breastfeeding with caution/enters breast milk

Mechanism of Action

• Bacteriocidal, beta-lactam agents that inhibit cell wall synthesis in susceptible bacteria by disrupting cross-linkage of peptidoglycans • Cefazolin is a first-generation agent with activity against Gram-positive and Gram-negative bacteria, broader Gram-negative spectrum than penicillins • Cefoxitin and cefotetan are second-generation agents with activity against anaerobes such as Bacteroides fragilis Uses

• Surgical prophylaxis for orthopedic, neurosurgery, and general surgery • Cefoxitin or cefotetan may be preferred if anaerobes are a concern

Onset

Time to peak at end of infusion, if given IM 0.5–2 hours Duration

Half life 90–150 minutes, prolonged in renal failure Metabolism

80–100% excreted unchanged in urine, minimal hepatic metabolism Adverse Effects

Fever, seizure, nausea, diarrhea, rash, hypersensitivity reactions, nephrotoxicity, elevation of INR

CLINICAL PEARLS

• Cefazolin is the preferred agent for surgical prophylaxis against common skin organisms • Cefoxitin and cefotetan have extended activity against anaerobes • INR elevation may result from reduced vitamin K absorption (altered GI flora); an exaggerated response to warfarin may also be seen • Subsequent generations of cephalosporin agents have increased activity against Gram negatives and lose some activity against Gram positives

TREATMENT DRUGS

Doxycycline (Vibramycin®) • Usual dose: 10000 g/day IV or PO, once daily or divided into 2 doses • Pediatric dosing (age >8 years) is 2–5 mg/kg/day, divided into 1 or 2 doses • Pregnancy risk D • Breastfeeding not recommended/enters breast milk

Mechanism of Action

Inhibits bacterial protein synthesis at 30S ribosomal subunit, bacteriostatic Uses

• Alternative agent in treatment of MRSA and VRE, cellulitis, PID, STDs, infections caused by unusual organisms • Broad spectrum of action

Onset

Time to peak (PO): 1.5–4 hours Duration

Half life 12–15 hours, increases to 22–24 hours after multiple doses, up to 25 hours in endstage renal disease Metabolism

Non-hepatic, excreted in feces and urine Adverse Effects

Pseudotumor cerebri, rare hepatotoxicity, hyperpigmentation, photosensitivity, diarrhea, increase in BUN, risk of superinfection

CLINICAL PEARLS

• May enhance neuromuscular blockade produced by non-depolarizing agents • Oral route of administration preferable if possible • Increase in BUN not due to renal toxicity, it is an antianabolic effect

TREATMENT DRUGS

Mupirocin (Bactroban®) • Usual dose (age ≥12): Topical ointment in single use tube, half of contents into each nare BID for 5 days (for elimination of MRSA colonization) • Pregnancy risk B • Breastfeeding unknown

Mechanism of Action

• Inhibits bacterial RNA synthetase, impairs protein synthesis

Uses

Elimination of MRSA colonization in high-risk patients or health care workers, impetigo, skin infections Onset

Minimal systemic absorption Duration

Found in stratum corneum for 72 hours after application Metabolism

Urine, some minor metabolism Adverse Effects

Headache, dizziness, local irritation/stinging/burning sensation, taste alteration, xerostomia, cough, rhinitis

CLINICAL PEARLS

• Routine use in surgical prophylaxis is unlabeled/controversial • Fungal/bacterial superinfection may occur • Permanent eradication is unlikely, recolonization eventually recurs in 30–100% of patients

TREATMENT DRUGS

Trimethoprim/sulfamethoxazole (TMP/SMX, Bactrim®, Septra®, co-trimoxazole) • Fixed dose combination (1:5) of 80 mg trimethoprim and 400 mg sulfamethoxazole in single

strength (SS) tablet • PO dose is 1 SS tablet every 6 hours or 1 double strength (DS) tablet every 12 hours • IV dose: 4–5 mg/kg (pediatric 8–12 mg/kg/day), based on trimethoprim component every 6–12 hours. Maximum daily dose PO or IV is 1,200 mg trimethoprim with 6,000 mg sulfamethoxazole. Doses require reduction in renal insufficiency • Pregnancy risk C • Breastfeeding not recommended

Mechanism of Action

Both agents are folate antagonists within bacterial cells, and are bacteriocidal in combination Uses

• Active against Gram-positive bacteria, Gram-negative bacilli, but inactive against anaerobes • Treatment of urinary tract infections, some respiratory tract infections, certain GI infections • MRSA, several unusual infections, and as a prophylactic anti-infective in immunosuppressed patients (e.g., Pneumocystis)

Onset

Time to peak: 1–4 hours after PO dosing Duration

Half life TMP: 8–11 hours, SMX: 10–13 hours Metabolism

Glomerular filtration and tubular secretion of unchanged drug Adverse Effects

Rash, fever, hypersensitivity reactions, nausea, vomiting, jaundice, arthralgias, hemolysis in G6-PDH patients, serum creatinine elevation, renal insufficiency, hyperkalemia, megaloblastic anemia, thrombocytopenia, granulocytopenia

CLINICAL PEARLS

• Adequate hydration and urine flow important to prevent crystalluria • Bone marrow depression more common in elderly and in those with or at risk for folate deficiency (alcoholics, malnourished) • GI adverse effects are common

ANTICHOLINERGICS Alan J. Kover, MD, PharmD Lori Gilbert, MD

TREATMENT DRUGS

Glycopyrrolate • Adjunct to neuromuscular blocking reversal: IV 0.2 mg for each 1 mg of neostigmine or 5 mg of pyridostigmine • Pregnancy Category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Competitive inhibitor of acetylcholine at muscarinic and ganglionic receptors Uses

• Reversal of bradycardia • Antisialogue • Reactive airway disease (relaxes bronchial smooth muscle) • Prevention of parasympathomimetic effects of acetylcholinesterase inhibitors

Onset

2–3 minutes Duration

30–60 minutes Metabolism

Renal excretion, approximately 80% is excreted unchanged in the urine Adverse Effects

Tachycardia, dry mouth

CLINICAL PEARLS

• Poorly lipid-soluble and will not cross the blood brain barrier, therefore does not have central effects

TREATMENT DRUGS

Atropine

• IV 0.5–1 mg for antivagal effects. 3 mg is usually a full vagolytic dose • Pregnancy Category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Competitive inhibitor of acetylcholine at muscarinic and ganglionic receptors Uses

• Reversal of bradycardia • Antisialogue • Prevention of parasympathomimetic effects of acetylcholinesterase inhibitors • Preemptively prior to second dose of succinylcholine

Onset

1 minute

Duration

30–60 minutes Metabolism

Atropine undergoes hydrolysis and some drug is excreted unchanged in the urine Adverse Effects

Tachycardia, sedation, dry mouth, mydriasis, cycloplegia

CLINICAL PEARLS

• Because the atropine molecule has lipid-insoluble portions, it cannot cross the blood brain barrier and cause centrally acting side effects • In small doses, it will actually produce a muscarinic activation and therefore can cause bradycardia if too small a dose is administered

TREATMENT DRUGS

Scopolamine • Prevention/treatment of PONV: 0.3–0.6 mg IM/IV/SC, pediatric—0.006 mg/kg SC • Preoperative sedation: 0.4–0.0.6 mg IM/IV/SQ, pediatric-6 months-3 years: 0.1–0.15 mg, age 3–6 years: 0.2–0.3 mg IV/IM/SC • Transdermal: 2.5 cm2 patch applied to skin behind ear • Pregnancy risk C, breastfeeding-caution/enters breast milk

Mechanism of Action

• Lipid soluble, tertiary amine that competitively antagonizes the effects of acetylcholine at

post-ganglionic muscarinic receptors peripherally as well as in the CNS • Has vagolytic/anticholinergic effects, reduces secretions, decreases GI motility/relaxes smooth muscle • Antagonizes histamine and serotonin • Depresses the reticular activating system and the cerebral cortex

Uses

• Prevention of motion sickness and PONV • Sedation/amnesia • Anti-sialogogue

Onset

• Oral, IM: 0.5–1 hour • IV: 10 minutes; peak effect: 20–60 minutes; may take 3–7 days for full recovery • Transdermal: Plasma levels detected within 4 hours, peak level within 24 hours

Duration

• Oral, IM: 4–6 hours • IV: 2.0 hours • Transdermal: T1/2 = 9.5 hours; Programmed to deliver approximately 1.0 mg of scopolamine at a constant rate to systemic circulation over 3 days

Metabolism

Hepatic-extensively metabolized and conjugated, <5% appears unchanged in urine Adverse Effects

• Xerostomia, possible tachycardia (less than atropine or glycopyrrolate), flushing, orthostasis, dizziness, drowsiness, mydriasis, blurred vision, amnesia, agitation, hallucinations, hyperthermia, warm/dry skin, constipation, urinary retention, possible anticholinergic syndrome (rare), idiosyncratic reaction/acute psychosis (rare) • Contraindications: – Narrow-angle glaucoma – Myasthenia Gravis – Paralytic Ileus – Tachycardia secondary to cardiac insufficiency – Hypersensitivity to belladonna alkaloids – Caution in renal impairment, CAD, heart failure, hepatic impairment, hiatal hernia/reflux esophagitis, prostatic hypertrophy/bladder outlet obstruction

CLINICAL PEARLS

• Differs from atropine in that it does not stimulate the medullary centers in the brain and does not cause an increase in respiration or elevation in BP • More potent anti-sialagogue than atropine. Ideal for anesthetics which require sedation and anti-sialagogue properties.

• Amnesia is additive to that produced by benzodiazepines • Additive toxicity with other anticholinergic agents, including ophthalmologic agents • May cause additive CNS depression with other CNS depressants, including volatile anesthetics • Administer Transdermal Scopolamine 4 hours preoperatively for optimum anti-emetic effect. Patient should wash hands after placement or removal-drug may inadvertently contact eye and cause mydriasis • Transdermal patch should be removed prior to an MRI, as skin burns may result • Physostigmine, a reversible anticholinesterase agent, may be administered for significant toxicity, including central anticholinergic syndrome. Usual dose is 0.5–2 mg IV/IM • Disease–related concerns – Caution in patients who will not tolerate tachycardia – Caution in GI/urinary tract obstruction – Caution in hepatic or renal impairment-may increase CNS toxicity – May exacerbate psychoses and seizure disorders – Caution in elderly patients

ANTICOAGULANTS AND REVERSALS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Aprotinin • Usual dosing 1–2 million kallikrein units, 20–30 minutes prior to sternotomy • Pregnancy category: B • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action Proteinase inhibitor Uses

• Antifibrinolytic agent for cardiopulmonary bypass • Prevention of massive perioperative blood loss

Duration

7–10 hours

Metabolism Renal

Adverse Effects

Increased risk of myocardial infarction, heart failure, anaphylaxis, cerebral artery occlusion, renal failure, shock, thrombocytopenia, thrombosis, encephalopathy

CLINICAL PEARLS

This product was removed from the market in May 2008 due to increased risk of mortality compared to other antifibrinolytic agents.

TREATMENT DRUGS

Heparin

• Cardiopulmonary bypass initiation: IV 150–400 units/kg • DVT/PE treatment: IV bolus 80 U/kg followed by maintenance dose of 18 U/kg and then maintain PTT levels 1.5–2.5 times normal levels • Angina: IV 60 units/kg and then maintain PTT levels 1.5–2.5 times normal values

Mechanism of Action

Enhances the activity of antithrombin III (>1000-fold) which inhibits conversion of prothrombin to thrombin as well as inhibits factors Xa, IXa, Xia, and XIIa Uses

Angina, acute myocardial infarction, deep venous thrombosis, pulmonary embolism, peripheral arterial occlusion Onset

IV immediate, subcutaneous 20–30 minutes Duration

• Peak IV effect occurs at 2 minutes • Peak SC effect is 2–4 hours • Half-life of IV anticoagulant effect is 1.5 hours

Metabolism Hepatic

Adverse Effects

• Hypotension, ecchymosis, alopecia, eczema, erythema, SIRS, tissue necrosis, hyperkalemia, DIC, hematoma, hemorrhage, hepatotoxicity, and hypersensitivity reaction • Heparin induced thrombocytopenia can result from a non-immune mechanism (Type I) or an autoimmune complication (Type II) after heparin exposure. Type 1 causes mild platelet aggregation with resultant platelet sequestration in the spleen, leading to thrombocytopenia. Type II, unlike other drug-induced thrombocytopenias, does not cause bleeding. Instead, it causes thrombosis and carries an increased risk for thromboembolic complications

CLINICAL PEARLS

The anticoagulant properties make heparin ideal for preventing thrombus formation while a patient is on cardiopulmonary bypass. It is also an agent that can be used in prevention of clotting in essentially any vascular structure

TREATMENT DRUGS

Protamine • Usual dosing: IV 1 mg for every 100 units of heparin administrated. Reduce dose if heparin was given >30 minutes previously • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Highly charged cation that ionically bonds to and inactivates heparin, a highly charged anion. It is intrinsically a weak anticoagulant Uses

Reversal of heparin Onset

30 seconds to 1 minute Duration 2 hours

Metabolism

• Hepatic • The protamine-heparin complex is cleared by the reticuloendothelial system

Adverse Effects

Flushing, nausea and vomiting, dyspnea, bradyarrhythmia, hypotension, pulmonary hypertension, anaphylactic reactions

CLINICAL PEARLS

• Dosing is determined by the time and dose of the last heparin administration. When overdosed in relationship to heparin, it functions as a weak anticoagulant • In patients with history of fish allergy or patients on protamine-containing insulin preparations, a severe allergic reaction can take place

TREATMENT DRUGS

Amicar • Usual dosing for hemorrhage: IV 4–5 g over 1 hour followed by an infusion of 1 g/hour for 8 hours • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Reversibly inhibits the binding of plasminogen to charged lysine sites on the surface of fibrin molecules, and thus prevents the conversion of plasminogen to plasmin Uses

Prevention of large amounts of surgical hemorrhage. Has been shown to decrease perioperative bleeding in cardiac surgery with CPB, orthotopic liver transplant, and major orthopedic surgery Onset

Immediate Duration

3–5 hours

Metabolism Renal

Adverse Effects

Bradycardia, hypotension, nausea and vomiting, dizziness, rash, thrombosis, rhabdomyolysis, renal failure

CLINICAL PEARLS

The use of aminocaproic acid is contraindicated for patients in DIC. In this scenario, the use of Amicar can lead to increased chance of thrombosis

ANTICONVULSANT PAIN ADJUNCTS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Gabapentin (Neurontin®) • PO 300–3,600 mg/day divided into 3 doses. Reduction in dose required in the elderly, and with impaired renal function • Pediatric age 3–12 years: PO 25–50 mg/kg/day divided into 3 doses • Pregnancy risk C • Breastfeeding caution, enters breast milk

Mechanism of Action

• Modulation of voltage-gated calcium receptors located presynaptically, decrease the release of excitatory neurotransmitters • Structurally similar to GABA but does not bind at GABA receptors • Exerts anticonvulsant and antinociceptive activity

Uses

Partial and secondarily generalized seizures, neuropathic pain, post-herpetic neuralgia, diabetic neuropathy, fibromyalgia, migraine prophylaxis Onset

May take 2–3 weeks for optimum effect Duration

Half life 5–7 hours, markedly prolonged in renal failure Metabolism

Excreted unchanged into urine Adverse Effects

Somnolence, dizziness, ataxia, fatigue, nystagmus, blurred vision, confusion, edema, weight gain

CLINICAL PEARLS

• Does not induce hepatic microsomal enzymes • Possible use in perioperative pain control, given 1–2 hours preoperatively • Should not be discontinued acutely in the perioperative period, as seizure frequency may increase • Can cause additive CNS depression when given with other CNS depressants

• May cause behavioral changes in children or those with underlying behavioral or developmental problems

TREATMENT DRUGS

Pregabalin (Lyrica®)

• Usual dose – PO 150–600 mg/day, in divided doses 2–3 times a day. Doses require reduction in patients with renal dysfunction – Pregnancy risk C – Breastfeeding not recommended, enters breast milk

Mechanism of Action

Similar to gabapentin. Modulation of voltage-gated calcium receptors located presynaptically, decreasing release of excitatory neurotransmitters Uses

• Partial or secondarily generalized seizures • Neuropathic pain • Fibromyalgia • Diabetic neuropathy • Post-herpetic neuralgia • Anxiety disorders

Onset

For pain management, about 1 week Duration

Half-life 6 hours Metabolism

Excreted in urine 90% unchanged, some minor inactive metabolites Adverse Effects

Somnolence, dizziness, ataxia, tremor, weight gain, xerostomia, blurred vision, angioedema, peripheral edema, headache, ataxia, confusion

CLINICAL PEARLS

• No significant drug interactions other than additive CNS depression • Does not induce hepatic microsomal enzymes • May cause euphoria and therefore is a DEA schedule V controlled substance • Should not be abruptly discontinued due to increased seizure risk

TREATMENT DRUGS

Topiramate (Topamax®) • Usual dose – PO 200–400 mg/day, once or divided into 2 doses. Reduced doses are required in the elderly and those with renal dysfunction – Pediatric (age <10): PO 50–400 mg/day, once or divided into 2 doses – Pregnancy risk D – Breastfeeding caution, enters breast milk

Mechanism of Action

• Blocks voltage-dependent sodium channels • Enhances GABA-mediated activity • Antagonizes excitatory receptors

Uses

• Partial or generalized seizures • Migraine or cluster headache prophylaxis • Diabetic neuropathy • Neuropathic pain

Onset

Time to peak 1–4 hours Duration

Half-life 21 hours Metabolism

70–80% unchanged drug into urine, some hepatic via CYP microsomal enzymes Adverse Effects

Drowsiness, dizziness, headache, ataxia, nervousness, confusion, paresthesias, weight loss, diplopia, acute glaucoma, impaired concentration/memory, nephrolithiasis, oligohidrosis, hyperthermia, hyperammonemia (additive risk if given with valproate)

CLINICAL PEARLS

• Rebound effects: Increased seizure incidence if discontinued abruptly, should be tapered over a period of weeks • Additive CNS depression occurs with administration of other CNS depressants • Has carbonic anhydrase inhibiting activity and may induce a hyperchloremic metabolic acidosis

TREATMENT DRUGS

Valproate (valproic acid: Depakene®, divalproexsodium: Depakote®) • Usual dose – Adult/pediatric: PO 250–3,000 mg/day in divided doses. Doses should be reduced in renal or hepatic impairment – Both products deliver same quantities of valproate ion – Extended release formulations are available – Pregnancy risk D – Breastfeeding not recommended, enters breast milk Mechanism of Action

Increases availability and enhances activity of GABA at inhibitory neurons Uses

• Seizure disorders • Migraine prophylaxis • Bipolar disorder • Mania • Diabetic neuropathy

Onset

Time to peak 4–17 hours (product-dependent) Duration

Half-life 9–16 hours Metabolism

• Extensively hepatic, with non-linear pharmacokinetics • Excreted into urine, 30–50% as glucuronide conjugate

Adverse Effects

Drowsiness, headache, visual disturbances, nausea, weight gain, androgenic side effects, tremor, thrombocytopenia, hair loss, liver failure, hyperammonemia, pancreatitis

CLINICAL PEARLS

• IV form (Depacon®) available • Additive CNS depression occurs when given with other CNS depressants • Additive risk of hyperammonemia with topiramate • Liver enzymes, platelet count, serum ammonia, and valproate levels should be monitored • Normal blood coagulation can be expected unless thrombocytopenia is present and is severe

TREATMENT DRUGS

Lamotrigine (Lamictal®) • Usual dose – PO 100–500 mg/day, doses may need reduction in renal or hepatic disease – Pediatric (age <13): 4.5–7.5 mg/kg/day – Pregnancy risk C – Breastfeeding not recommended, enters breast milk

Mechanism of Action

• Membrane stabilization via inhibition of voltage-gated sodium channels • Inhibits excitatory neurotransmitter release (glutamate)

Uses

• Partial or secondarily generalized seizures • Bipolar disorder

Onset

Time to peak 1–11 hours, product-dependent Duration

Half-life 25–33 hours, prolonged in elderly Metabolism

Hepatic and renal to glucuronide conjugate, (inactive), which is subsequently excreted in urine Adverse Effects

Dizziness, ataxia, somnolence, headache, diplopia, nausea, rash, insomnia, Stevens–Johnson syndrome, hepatitis, adverse cognitive effects

CLINICAL PEARLS

• Generally fewer adverse effects than carbamazepine or phenytoin • Recent FDA warning issued for rare incidence of aseptic meningitis • Caution advised when therapy includes other antiepileptic agents or estrogen-containing products, including dose changes, due to drug interactions • If the drug requires discontinuance, should taper doses over 2 weeks, as increased seizure activity may occur • Additive CNS depression occurs if other CNS depressants given

TREATMENT DRUGS

Clonazepam (Klonopin®)

• Usual dose – PO 1.5–8 mg/day in 2–3 divided doses; reduce dose in elderly patients or those with hepatic disease – Pediatric: PO 0.1–0.2 mg/kg/day in 2–3 divided doses – Pregnancy risk D – Breastfeeding not recommended, enters breast milk

Mechanism of Action

Similar to other benzodiazepines, enhances activity of GABA-mediated inhibition of neuronal activity Uses

• Seizures that are resistant to other treatments • Burning mouth syndrome • Neuralgias • Restless leg syndrome

Onset

20–60 minutes Duration

≤12 hours

Metabolism

Extensive hepatic, via CYP3A4, to inactive glucuronide or sulfate conjugates that are excreted in urine Adverse Effects

Drowsiness, ataxia, behavioral disorders, amnesia, paradoxical reactions, CNS depression

CLINICAL PEARLS

• Like other benzodiazepines, may have withdrawal syndrome upon abrupt discontinuance • Additive CNS depression when used with other CNS depressants • Many drug interactions • A DEA schedule IV controlled substance • Flumazenil effectively reverses CNS depression

TREATMENT DRUGS

Carbamazepine (Tegretol®, Carbatrol®) • Usual dose – PO 800–1,600 mg/day. Reduced doses may be needed in renal or hepatic impairment

– Pediatric PO: 400–800 mg/day – Pregnancy risk D – Breastfeeding not recommended, enters breast milk

Mechanism of Action

Decreases sodium flux across cell membranes and synaptic transmission in thalamic structures that result in anticonvulsant, antineuralgic, antiarrhythmic, anticholinergic, and antidepressant activity (structurally related to tricyclic antidepressants) Uses

• Partial or secondarily generalized seizure disorders • Bipolar disorder • Trigeminal/glossopharyngeal neuralgias

Onset

Time to peak unpredictable Duration

Initial half life—parent drug 25–65 hours, epoxide 25–43 hours, both change over 3–5 weeks due to autoinduction Metabolism

Extensive hepatic metabolism, via CYP3A4, to active epoxide metabolite that is mostly excreted into urine Adverse Effects

Drowsiness, blurred vision, diplopia, headache, dizziness, ataxia, nausea, cognitive changes, leukopenia, hyponatremia/SIADH, blood dyscrasias, rash, Stevens–Johnson syndrome, mild anticholinergic activity, dysrhythmias, cardiac conduction defects

CLINICAL PEARLS

• Induces own metabolism and serum levels fall after a few weeks of use • Stevens–Johnson syndrome is incidence higher in Asian populations • Additive CNS depression with other CNS depressants • High potential for drug interactions, induces several CYP microsomal enzymes Nondepolarizing neuromuscular blockers require higher, more frequent dosing due to increased metabolism

TREATMENT DRUGS

Phenytoin (Dilantin®) • IV loading dose 15–20 mg/kg, not to exceed 50 mg/minute, then 100 mg every 6–8 hours in adults. Dosages should be based on adjusted body weight in the obese, and may need

adjustment guided by serum-free phenytoin levels in renal/hepatic dysfunction or hypoalbuminemia. Lower doses used in the elderly • Pediatric: PO 300–600 mg/day once or up to 3 divided doses (depends on formulation). Pediatric maintenance doses vary by age/weight • Pregnancy risk D • Breastfeeding not recommended, enters breast milk

Mechanism of Action

Stabilizes neuronal cell membranes via modulation of sodium flux. Shortens action potential and prolongs effective refractory period in cardiac tissue Uses

• Seizure disorders including grand mal, status epilepticus, prophylaxis in neurosurgery • Trigeminal neuralgia

Onset

• IV 0.5–1 hour • PO: Time to peak for immediate release 2–3 hours

Duration

Average half-life 22 hours Metabolism

• Hepatic, highly variable, Michaelis-Menten kinetics • Metabolite undergoes enterohepatic recirculation • Conjugates are excreted in the urine

Adverse Effects

Nystagmus, drowsiness, ataxia, diplopia, gingival hyperplasia, slurred speech, cerebellar atrophy, coarsening of facial features, hirsutism, rash, hypersensitivity reactions, cognitive impairment, blood dyscrasias

CLINICAL PEARLS

• Fosphenytoin is an alternate, water-soluble injectable formulation, without the propylene glycol co-solvent in the standard phenytoin injectable • Hypotension may occur if injected too rapidly • Exhibits non-linear, saturable pharmacokinetics with a narrow therapeutic index • Many drug interactions, also is a hepatic enzyme inducer. In chronic users, dose of nondepolarizing neuromuscular blockers may need increased or be administered more frequently • Seizure frequency may increase if discontinued abruptly

ANTIDEPRESSANTS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Selective Serotonin Reuptake Inhibitors (SSRIs) Mechanism of Action

Selectively inhibits serotonin reuptake into presynaptic neurons, with little effect on norepinephrine or dopamine Uses

• Antidepressant • Anxiety disorders • Adjunct in some chronic pain disorders

Adverse Effects

Somnolence or insomnia, tremor, nausea, diarrhea, headache, dizziness, sexual dysfunction, weight gain, platelet inhibition, serotonin syndrome, SIADH (especially in elderly). Withdrawal syndrome, nervousness, anxiety, paresthesias, irritability, confusion, dysphoria, seizures. Increased risk of suicide in adolescents Table 1 Selective serotonin reuptake inhibitors Table 2 Serotonin norepinephrine reuptake inhibitors

CLINICAL PEARLS

• SSRIs, SNRIs, and bupropion are generally drugs of choice for depression and are considered to have equal efficacy • Withdrawal syndrome can occur with abrupt cessation of use—consider continuing daily dose throughout perioperative period unless high risk for bleeding or high-risk procedure • Bleeding risk is increased in patients taking other medications that impair coagulation • Should not be used concurrently with MAO inhibitors as risk of serotonin syndrome increases • May induce mania in patients with bipolar disorders • May prolong the QT interval especially in patients on other medications that prolong the QT • May lower the seizure threshold

TREATMENT DRUGS

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

Mechanism of Action

Inhibition of serotonin and norepinephrine reuptake at synapses, weak effect on dopamine reuptake. No significant effect on muscarinic, alpha-receptors or MAO Uses

• Depression • Anxiety/stress disorders • Chronic pain syndromes • Duloxetine indicated for fibromyalgia, diabetic neuropathy

Adverse Effects

Similar to SSRIs, also diaphoresis, tachycardia, urinary retention, increase in blood pressure, hypercholesterolemia. Weight loss with venlafaxine. Severe hepatotoxicity with duloxetine. Withdrawal syndrome similar to SSRIs Table 3 Tricyclic antidepressants

CLINICAL PEARLS

• Considered equivalent in efficacy to SSRIs for depression • Increased risk of suicide in adolescents • Consider maintaining therapy during perioperative period, unless high risk of bleeding, a high-risk procedure is planned, or patient is taking other medications that impair coagulation • May lower seizure threshold • Should not be used with MAO inhibitors (risk of serotonin syndrome increased) • May induce mania in patients with bipolar disorder • Many drug interactions exist

TREATMENT DRUGS

Tricyclic Antidepressants Mechanism of Action

• Decreases synaptic reuptake of serotonin and norepinephrine; may also downregulate serotonin and beta-adrenergic receptors • Have anticholinergic and anti-α1 activity

Uses

• Depression • Anxiety disorders • Chronic/neuropathic pain • Myofascial pain

• Peripheral neuropathies • Amitriptyline used for migraine prophylaxis

Adverse Effects

Urinary retention, constipation, xerostomia, blurred vision, confusion, sedation, weight gain, orthostatic hypotension, sexual dysfunction, dysrhythmias/prolongs QT interval, lowers seizure threshold

CLINICAL PEARLS

• Equal efficacy to SSRI/SNRI, but adverse effects more common/severe • These agents should be held in the perioperative period (unless patients have been on longterm high-dose therapy); they have a relatively long half-life so withdrawal syndrome not as common • Have significant sedating and anticholinergic effects, as well as α blocking activity, and additive QT prolongation; Torsades is possible • Should not be used with MAO inhibitors • Many drug interactions • Lower doses are usually utilized for chronic pain syndromes

TREATMENT DRUGS

Bupropion (Wellbutrin®) • Reduction of dose may be required for hepatic or renal dysfunction, or in the elderly • Pregnancy Category: C • Breastfeeding not recommended

Mechanism of Action

• Has effects on dopaminergic and noradrenergic receptors in the brain • Metabolites impairs reuptake of norepinephrine • Does not impair serotonin reuptake

Uses

• Antidepressant • Smoking cessation • ADHD

Onset

Time to peak 2–5 hours, metabolite 3–7 hours, product-dependent Duration

Half-life parent drug 12–30 hours, metabolites 20–37 hours Metabolism

Extensive hepatic via CYP2B6 and others, to active metabolites that are excreted in the urine, some in feces Adverse Effects

Anxiety, headache, hypertension, tachycardia, xerostomia, insomnia, nausea, anorexia, seizures (higher doses), hypersensitivity reactions

CLINICAL PEARLS

• Alternative in patients who cannot tolerate weight gain, sedation, and sexual side effects of other antidepressants • Should not be used in those taking MAO inhibitors, as it increases the risk of serotonin syndrome • Several drug interactions (a strong inhibitor of CYP2D6) Table 4 MAO inhibitors

TREATMENT DRUGS

MAO Inhibitors • Pregnancy Category: C for all • Breastfeeding not recommended

Mechanism of Action

• Increases endogenous concentration of norepinephrine, serotonin, and dopamine in the CNS and PNS by inhibiting their metabolism by MAO • 2 isoenzymes exist—MAO-A and MAO-B. MAO-B is the isoenzyme that is predominately responsible for dopamine metabolism Uses

• Atypical or severe depression • MAO-B inhibitors are used in Parkinson disease

Adverse Effects

Sleep disturbances, orthostatic hypotension, edema, sexual dysfunction, weight gain, anticholinergic effects

CLINICAL PEARLS

• Not commonly used due to food–drug interactions and adverse effects • Ideally, should be weaned off 2 weeks prior to surgery, but may not be possible if medical/psychiatric status warrants continuation • May result in hypotension with general or neuraxial anesthesia. Direct-acting adrenergic agonists should be administered at lower doses to treat hypotension (risk of an augmented hypertensive response)

• Risk of serotonin syndrome when given with SSRIs, SNRIs, bupropion, meperidine, linezolid, indirect-acting sympathomimetics, dextromethorphan, triptan, antimigraine drugs, tramadol, and St. John’s wort • A hypertensive crisis is possible if tyramine-containing foods are consumed • Agents which preferentially inhibit MAO-B at usual doses have less risk of adverse events, and may not need to be discontinued • Opioids, such as fentanyl, sufentanil, and alfentanil (chemically similar to meperidine), may increase the risk of serotonin syndrome (uncommon)

ANTIEMETIC AGENTS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Ondansetron (Zofran®) • Prophylaxis IV or IM dose 4 mg, 30 minutes prior to end of surgery • Prophylaxis PO dose 16 mg, 1 hour prior to surgery – Pediatric: – ≤40 kg 0.1 mg/kg – >40 kg 4 mg, one time dose – Pregnancy Category: B – Breastfeeding unknown Mechanism of Action

Selective antagonist at 5-HT3 receptors in the chemoreceptor trigger zone centrally and at vagal nerve terminals in the gut Uses

• Prophylaxis of postoperative nausea and vomiting • Chemotherapy-induced nausea and vomiting (32 mg dose) • Radiation-induced nausea and vomiting • Pruritus

Onset

30 minutes Duration

4–6 hours

Metabolism

• Hepatic via CYP3A4 predominately (inducible), 1A2 and 2D6 also • No adjustment required for renal failure or in the elderly • Should not exceed 8 mg/day in severe hepatic disease

Adverse Effects

Headache, dizziness, sedation, constipation, diarrhea, increased liver enzymes, may prolong QT interval and predispose to torsades de pointes especially when given with other drugs that prolong QT. May mask ileus or bowel obstruction. Dyskinesia has been reported if administered too rapidly

CLINICAL PEARLS

• May also be used for pruritus (8 mg) • Dose may be repeated after 4–6 hours if nausea or vomiting persists. 4 mg IV dose should be administered over at least 2 minutes. 8 mg IV dose may be more efficacious than a 4 mg dose for PONV • Combining with dexamethasone may improve efficacy

TREATMENT DRUGS

Dolasetron (Anzemet®) • Prophylaxis IV 12.5 mg prior to end of surgery • PO dose 100 mg, 30 minutes prior to surgery • Pediatric – Age <2: IV 0.35 mg/kg up to 12.5 mg – Age >2: IV 1.2 mg/kg, max 100 mg • Pregnancy risk B • Breastfeeding unknown

Mechanism of Action

Selective antagonist at 5-HT3 receptors in the chemoreceptor trigger zone centrally and at vagal nerve terminals in the gut Uses

• Prophylaxis and treatment of postoperative nausea and vomiting • Now contraindicated for chemotherapy-induced nausea and vomiting in the IV form

Onset

15–30 minutes Duration

6–8 hours

Metabolism

• Rapidly metabolized to the active form, predominately excreted in urine, also metabolized by CYP3A4 and 2D6 • No dosage adjustment required for hepatic or renal dysfunction, or in geriatric populations

Adverse Effects

Headache, dizziness, sedation, bradycardia, diarrhea, prolongation of QT interval, and increased risk of torsades de pointes

CLINICAL PEARLS

• Dolasetron is a prodrug, hydrodolasetron is the active form • Administration with dexamethasone improves efficacy • Caution with patients predisposed to prolonged QT or use of other agents that prolong the QT interval, as well as patients with hypokalemia and hypomagnesemia • Equivalent efficacy to other 5-HT3 antagonists

TREATMENT DRUGS

Granisetron (Kytril®) • Prophylaxis IV 1 mg over 30 seconds at the end of surgery • Oral and patch form available • Pregnancy Category: B • Breastfeeding unknown

Mechanism of Action

Selective antagonist at 5-HT3 receptors in the chemoreceptor trigger zone centrally and at vagal nerve terminals in the gut Uses

• Postoperative nausea and vomiting prophylaxis and treatment • Chemotherapy-induced nausea and vomiting • Radiation-induced nausea and vomiting

Onset

Rapid

Duration 24 hours

Metabolism

• Hepatic, some metabolites may be active • Dose adjustments are not required in hepatic or renal insufficiency or in geriatric populations

Adverse Effects

Headache, constipation, diarrhea, abdominal pain, weakness, dizziness, prolongation of QT interval, and increased risk of Torsades de Pointes

CLINICAL PEARLS

• Duration may be longer than other 5-HT3 antagonists (except for palonosetron) • Dexamethasone may improve efficacy • Caution with other drugs/conditions that prolong the QT interval

TREATMENT DRUGS

Palonosetron (Aloxi®) • IV 0.075 mg over 10 seconds prior to induction • No oral form available • Pregnancy Category: B • Breastfeeding unknown

Mechanism of Action

Selective antagonism at 5-HT3 receptors in the chemoreceptor trigger zone centrally and at vagal nerve terminals in gut Uses

• Postoperative nausea and vomiting prophylaxis • Chemotherapy-induced nausea and vomiting prophylaxis

Onset

30 minutes Duration

At least 24 hours Metabolism

• Hepatic by multiple CYP enzymes to inactive metabolites, and renal excretion • Prolonged half-life (>40 hours) • No dosage adjustments required for hepatic or renal insufficiency, or in geriatric populations

Adverse Effects

Headache, weakness, constipation, bradycardia, prolongation of QT interval, and increased risk of Torsades de Pointes

CLINICAL PEARLS

• Expensive • Superior to other 5-HT3 antagonists in prevention of delayed postoperative nausea and vomiting • Efficacy for up to 120 hours for chemotherapy patients

TREATMENT DRUGS

Aprepitant (Emend®) • PO 40 mg, 3 hours prior to induction of anesthesia

• Pregnancy Category: B • Breastfeeding unknown

Mechanism of Action

• Neurokinin 1/substance P inhibitor • Augments activity of 5-HT3 antagonists and dexamethasone for nausea and vomiting control

Uses

• Prophylaxis of postoperative nausea and vomiting • Chemotherapy-induced nausea and vomiting

Onset

Peak serum level 3 hours after oral dose Duration

At least 24 hours, possibly up to 48 hours Metabolism

• Hepatic CYP3A4 and other CYP isoenzymes • High potential for drug interactions with substrates of 3A4 • No dosage adjustment required for mild-to-moderate liver dysfunction, unknown for severe • No dosage adjustment required for renal failure or for elderly

Adverse Effects

Fatigue, dizziness, hypotension, tachycardia, bradycardia, nausea, constipation, weakness, hiccups

CLINICAL PEARLS

• IV form, fosaprepitant (prodrug of aprepitant), is not FDA indicated for postoperative nausea and vomiting to date • Prolonged effect, up to 24 hours for PONV • Expensive

TREATMENT DRUGS

Dexamethasone (Decadron®)

• Postoperative nausea and vomiting IV 4–8 mg • Airway edema (adult/pediatric): 0.5–2 mg/kg/day divided over 4 doses every 6 hours • Cerebral edema IV 10 mg (pediatric 1–2 mg/kg) immediately, followed by 4 mg every 6 hours (pediatric 1–1.5 mg/kg/day) until maximum response, then tapered • Addisonian shock IV 4–10 mg once, if unresponsive shock, up to 40 mg can be used • Pregnancy Category: C • Breastfeeding unknown

• Oral forms are available

Mechanism of Action

• Unknown for antiemetic activity • Impairs neutrophil function, decreases inflammatory mediator production, suppresses immune response

Uses

• Prophylaxis of postoperative nausea and vomiting • Anti-inflammatory, immunosuppressant • Treatment of cerebral edema • Treatment of airway edema • Treatment of shock (Addisonian or unresponsive to other steroids)

Onset

Prolonged, given preoperatively or soon after anesthesia induction Duration

• Up to 48 hours for a single dose for PONV • Metabolic effects may last for 72 hours

Metabolism

• Hepatic, mostly via CYP3A4, other isoenzymes contribute • No dosage adjustments needed for renal dysfunction • Use smallest possible doses in the elderly

Adverse Effects

• GI upset, fluid retention, hyperglycemia, adrenal suppression, poor wound healing, insomnia, nervousness, psychiatric disturbances, myopathy, immune suppression • Rapid administration may produce perineal discomfort

CLINICAL PEARLS

• Most adverse effects occur with chronic use • Increases efficacy of PONV prophylaxis when combined with a 5-HT3 antagonist, droperidol, and others • Potential for prolonged effect (up to 48 hours); use with caution in diabetics • Many potential drug interactions • Little mineralocorticoid effect • Contraindicated in patients with invasive fungal infections • Doses should be tapered after prolonged use

TREATMENT DRUGS

Droperidol (Inapsine®)

• PONV IV 0.625–1.25 mg administered slowly, may be repeated every 6 hours • PONV IM 2.5 mg • No oral forms available • Pediatric IV 0.01–0.015 mg/kg, max 1.25 mg (consensus guidelines) • Pregnancy Category: C • Breastfeeding unknown

Mechanism of Action

Antagonist at dopamine receptors in the chemoreceptor trigger zone Uses

• Prophylaxis and treatment of postoperative nausea and vomiting • Chemotherapy-induced nausea and vomiting • Antipsychotic

Onset

3–10 minutes Duration

2–4 hours, may extend to 12 hours Metabolism

• Hepatic, to inactive metabolites excreted by kidney • No specific dosage adjustments stated for hepatic or renal dysfunction, or for geriatric patients, but dose reductions should be considered Adverse Effects

• Contraindicated in patients with a prolonged QT interval due to the risk of Torsades de Pointes • FDA Black Box Warning for doses exceeding 2.5 mg • Extrapyramidal symptoms, hypotension/orthostasis, tachycardia, neuroleptic malignant syndrome, sedation, restlessness

CLINICAL PEARLS

• Caution in patients on other medications or conditions that prolong the QT interval. 12-lead EKG needed prior to use, and 2–3 hours of EKG monitoring required after administration • Has peripheral alpha-blocking activity, mild anticholinergic activity • FDA Black Box status exists for doses exceeding those generally used for PONV. May combine with dexamethasone to further increase efficacy • Little to no respiratory depression

TREATMENT

DRUGS

Haloperidol (Haldol®) • Postoperative nausea and vomiting IV/IM 0.5–2 mg IV or IM • Tranquilization IV 2–10 mg IV for tranquilization • Oral/liquid forms available • Pregnancy Category: C • Breastfeeding not recommended

Mechanism of Action

Antagonist at dopamine receptors in chemoreceptor trigger zone Uses

• Postoperative nausea and vomiting (non-labeled use) • Schizophrenia • Delirium • Agitation

Onset

30–60 minutes as tranquilizer Duration

IV half-life 14 hours Metabolism

• Hepatic to several metabolites, one is active, CYP3A4 and glucuronidation • Slower dose titration recommended in elderly, no changes required in renal insufficiency

Adverse Effects

Extrapyramidal reactions, QT prolongation and potential for dysrhythmia, hypotension, CNS depression, neuroleptic malignant syndrome, sedation

CLINICAL PEARLS

• Same precautions and monitoring as droperidol • No Black Box Warning for use in PONV, but has a warning for increased risk of death in the elderly with dementia • Little to no respiratory depression

TREATMENT DRUGS

Metoclopramide (Reglan®) • Prophylaxis PONV IV/IM 10 mg near end of surgery • Oral liquid available

• Pregnancy Category: B • Breastfeeding with caution/enters breast milk

Mechanism of Action

• Blocks dopamine receptors in the chemoreceptor trigger zone • Enhances cholinergic activity in the upper GI tract that increases motility and lower esophageal sphincter tone

Uses

• Gastroparesis • PONV prophylaxis • Chemotherapy-induced nausea and vomiting prophylaxis • GERD

Onset

1–3 minutes IV Duration

1–2 hours

Metabolism

• Renal excretion (85%), dose reduction by 50% required for creatinine clearance <40 mL/minute • Minor hepatic metabolism; no dose changes required for hepatic dysfunction • Reduce dose by 50% in geriatric populations

Adverse Effects

Contraindicated in patients with bowel obstruction, GI hemorrhage, perforation, or pheochromocytoma. Extrapyramidal reactions, tardive dyskinesia, neuroleptic malignant syndrome, drowsiness, restlessness may occur

CLINICAL PEARLS

• 10 mg dose is ineffective for PONV, 20 mg may have greater efficacy, but more adverse effects • Abrupt discontinuation may produce dizziness, headache, nervousness

TREATMENT DRUGS

Promethazine (Phenergan®) • PONV IV 6.25–25 mg, may repeat every 4–6 hours • PONV IM 12.5–25 mg • Pediatric (PO, rectal, IM, IV): 0.25–1 mg/kg, up to 25 mg, every 4–6 hours • Pregnancy Category: C

• Breastfeeding not recommended

Mechanism of Action

• Anticholinergic and antihistaminic effects in chemoreceptor trigger zone • Little dopamine receptor blockade

Uses

• Postoperative nausea and vomiting • Motion sickness • Sedation • Adjunct with opiates for analgesia

Onset

IV 5 minutes, IM/PO 20 minutes Duration

4–6 hours

Metabolism

• Hepatic oxidation, has active metabolites • No dosage adjustment required for renal failure • Low end of dosage range used in geriatric patients

Adverse Effects

Sedation, extrapyramidal reactions, orthostatic hypotension due to alpha-1-blockade, CNS and respiratory depression, anticholinergic side effects

CLINICAL PEARLS

• Caution with extravasation, can cause vascular necrosis, tissue sloughing • 6.25 mg IV dose adequate for PONV, is less sedative. Doses >6.25 mg IV should be decreased by 25–50% when used with opiates or other CNS/respiratory depressants

TREATMENT DRUGS

Prochlorperazine (Compazine®) • PONV treatment IV 2.5–10 mg IV slowly, <5 mg/ minute. Prophylaxis IV 5–10 mg may be given 15–30 minutes preinduction for prophylaxis • Deep IM 5–10 mg, may repeat in 3–4 hours, max dose 40 mg/day • Rectal suppository available • Pediatric (age >2) IM 0.13 mg/kg/dose • Pregnancy—risk of jaundice, abnormal reflexes, and extrapyramidal movements in newborns • Excretion into breast milk unknown

Mechanism of Action

• Blocks dopaminergic receptors in the chemoreceptor trigger zone • Anticholinergic • Alpha-1-blockade • A phenothiazine with inferior antipsychotic activity

Uses

• Prophylaxis and treatment of PONV • Migraine or severe headache

Onset

Peak IV effect 30–60 minutes Duration

4–6 hours IV or IM Metabolism

Hepatic, to active metabolite. Use lower end of dose range in geriatric patients Adverse Effects

Extrapyramidal reactions, hypotension, orthostasis, sedation, drowsiness, CNS depression, anticholinergic side effects. Phenothiazines may prolong QT interval/predispose to Torsades de Pointes

CLINICAL PEARLS

• High incidence of dystonia, tardive dyskinesia, and extrapyramidal effects, especially in elderly, neuroleptic malignant syndrome • Less sedating than promethazine

ANTIHISTAMINES Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Diphenhydramine (Benadryl®) • Usual dose: IV 50 mg for anaphylaxis/severe allergic reaction, dystonia, prophylaxis for contrast administration, 25–50 mg for antiemetic, minor allergic reaction uses • Similar doses may be given IM or PO, 30–60 minutes prior to anticipated need • Pediatric 0.5–1.0 mg/kg/dose for acute reactions • Pregnancy risk B • Breastfeeding not recommended

Mechanism of Action

• Competitive antagonist of histamine at H1 receptors in the respiratory tract, GI tract, and vasculature • Also has some anticholinergic (bronchodilation, antisialogogue, and treatment of dystonic reactions) and antiserotonergic (antiemetic) activity Uses

• Allergic reactions • Anaphylaxis • Sedation (useful in Parkinson’s due to its anticholinergic effects) • Dystonic reactions • Antipruritic • Antiemetic • Motion sickness • Prophylaxis for histamine release from contrast

Onset

15–30 minutes, peak in 2–4 hours Duration

4–6 hours

Metabolism

Hepatic via CYP2D6 to an active metabolite, other cytochromes (minor); renal excretion unchanged (minor) Adverse Effects

Sedation, xerostomia, dizziness, CNS depression, urinary retention, constipation, tachycardia,

ileus

CLINICAL PEARLS

Caution in patients who cannot tolerate anticholinergic adverse effects. Can be very sedating and cause confusion, especially in elderly

TREATMENT DRUGS

Hydroxyzine (Vistaril®, Atarax®) • Usual dose: IM 25–100 mg, PO 50–100 mg • Pediatric 0.6–1.1 mg/kg/dose • Not recommended in the elderly • Pregnancy not recommended • Breastfeeding not recommended

Mechanism of Action

• Competitive antagonist of histamine at H1 receptors in the respiratory tract, GI tract, and vasculature • Also has some anticholinergic effects

Uses

• Allergic reactions • Anti-anxiety • Antiemetic/motion sickness • Preoperative sedation • Antipruritic

Onset

PO 30 minutes, IM rapid Duration

Antihistaminic effects 2–36 hours, antipruritic 1–12 hours Metabolism

Hepatic to active metabolites, including cetirizine; excreted in the urine Adverse Effects

Sedation, confusion, dizziness, CNS depression, xerostomia, urinary retention, blurred vision

CLINICAL PEARLS

• Should not be given IV or SC • Should not be used in the elderly as it may cause undesired anticholinergic effects, including

confusion

ANTISPASMODIC AGENTS/DANTROLENE Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Tizanidine (Zanaflex®) • Initial dose PO 4 mg, increase 2–4 mg every 6–8 hours as needed for adequate relaxation of muscle tone • No geriatric guidelines exist, use caution • Should be avoided in hepatic disease, may need to reduce dose with renal impairment • Pregnancy Category: C • Breastfeeding: Not recommended

Mechanism of Action

• Alpha-2 agonist (related to clonidine) that decreases excitatory input to alpha motor neurons; has antinociceptive activity at presynaptic alpha-2 sites Uses

• Spasticity • Muscle relaxation • Unlabeled uses for back pain • Migraine • Trigeminal neuralgia • Acute pain

Onset

1–2 hours for decrease in spasticity. Peak response takes about 8 weeks Duration

3–6 hours

Metabolism

Extensive hepatic 1st pass metabolism via CYP1A2; inactive metabolites excreted in urine (60%) and feces Adverse Effects

Hypotension, bradycardia, somnolence, dizziness, visual hallucination, xerostomia, weakness

CLINICAL PEARLS

• Blood pressure lowering occurs at 1/10–1/50th the potency of clonidine. Additionally, hypotension is additive when given with antihypertensive agents or anesthetic agents

• Additive CNS depression when given with other CNS depressants • Levels may increase in patients taking other substrates of CYP1A2 (e.g., ciprofloxacin, haloperidol, olanzapine) • Monitor liver enzymes prior to and during use • Has the same precautions for abrupt withdrawal as clonidine, as well as risk of hypertonia

TREATMENT DRUGS

Baclofen (Lioresal®) • Pregnancy Category: B • Breastfeeding compatible

Mechanism of Action

• Inhibits mono- and polysynaptic reflexes at the spinal cord level via presynaptic inhibitory GABA receptors. Hyperpolarizes afferent terminals with inhibition of muscle spasticity

Uses

Treatment of spasticity, in patients with multiple sclerosis or spinal cord lesions Onset

• Oral dosing 3–4 days, peak effect in 5–10 days • Intrathecal dosing 30–60 minutes if bolused, 4 hours for peak response • If infused, onset 6–8 hours, peak effect 24–48 hours.

Duration

Single intrathecal dose 4–8 hours. Effect progressively decreases during chronic therapy. Metabolism

85% excreted unchanged in urine and feces, only 15% metabolized. May need to reduce dose for renal insufficiency Adverse Effects

Drowsiness, vertigo, muscle weakness, ataxia, slurred speech, hypotonia, psychiatric disturbances, confusion, seizure, hypotension, polyuria. Constipation with intrathecal dosing common

CLINICAL PEARLS

• Should not be abruptly discontinued and needs to be tapered off if discontinuing. Baclofen has an FDA Black Box Warning for rebound spasticity, muscle rigidity, rhabdomyolysis, obtundation, and hyperpyrexia, which tend to be more severe for intrathecal administration. Rebound effect usually occurs within 48 hours of discontinuation • Preservative-free preparations should be used intrathecally • Additive CNS depression occurs when administered with other CNS depressants

TREATMENT DRUGS

Carisoprodol (Soma®) • Not recommended for use in geriatric populations • Use with caution in patients with hepatic or renal disease • Pregnancy Category: C • Breastfeeding caution

Mechanism of Action

• Mild antispasmodic action, possibly by decreasing polysynaptic neuron transmission in spinal cord and reticular formation • Meprobamate metabolite has sedative and anxiolytic activity

Uses

Short-term (2–3 weeks) use in musculoskeletal pain/muscle spasm, not generally used for spastic disorders Onset

30 minutes Duration

4–6 hours

Metabolism

Hepatic, metabolized to meprobamate (an active metabolite) by CYP2C19, which is excreted in urine Adverse Effects

Drowsiness, dizziness, seizure, anticholinergic effects. Paradoxical CNS simulation may occur

CLINICAL PEARLS

• CNS depression occurs and is additive when used with other CNS depressants • Has abuse potential, more likely in patients with a history of drug or alcohol abuse. Physical and psychological dependence, as well as tolerance and drug withdrawal upon discontinuation may occur • Drug interactions may occur with other drugs metabolized by CYP2C19 (e.g., clopidogrel and proton pump inhibitors)

TREATMENT DRUGS

Cyclobenzaprine (Flexeril®)

• Pregnancy Category: B • Breastfeeding caution

Mechanism of Action

Reduces tonic somatic output of alpha and gamma motor neurons in CNS Uses

Skeletal muscle spasm associated with musculoskeletal injury Onset

Within 1 hour of oral dose, for peak response 1–2 weeks with continued use Duration

Single dose 12–24 hours Metabolism

Hepatic via multiple CYP isoenzymes to inactive metabolites excreted in urine. Some unchanged drug excreted in feces Adverse Effects

Drowsiness, dizziness, xerostomia, anticholinergic effects, tachycardia, arrhythmia, heart block, hypertension, muscle weakness

CLINICAL PEARLS

• Chemically related to tricyclic antidepressants, similar potential adverse effects, and delayed peak response • Additive CNS depression with other depressants and additive anticholinergic effects may occur, as well as prolongation of the QT interval • Potential for hypertensive crisis if given with MAO inhibitors, and serotonin syndrome if given with serotonergic reuptake inhibitors such as tricyclic antidepressants and serotonin specific reuptake inhibitors • Not effective for spasticity

TREATMENT DRUGS

Dantrolene (Dantrium®, Revonto®)

• Usual dose (adult/pediatric): Malignant hyperthermia crisis (doses per mhaus.org) 2.5 mg/kg IV, repeat in 10 minutes until symptoms subside or 10 mg/kg total dose is reached. Sometimes up to 30 mg/kg has been required to abort an MH crisis • After the acute phase, 1 mg/kg IV every 4–6 hours, or 0.25 mg/kg/hour for at least 24 hours, possibly for 1–3 days (further need is determined by the patient’s response). Alternatively, if the patient can tolerate oral pills, PO 4–8 mg/kg/day in 4 divided doses

Mechanism of Action

Inhibits release of calcium from sarcoplasmic reticulum in skeletal muscle tissue, reducing the amount available for mediating muscle contraction Uses

• Malignant hyperthermia treatment and prophylaxis • Spasticity due to upper motor neuron lesions • Neuroleptic malignant syndrome

Onset

Rapid/based on dose for MH crisis Duration

6–18 hours for MH prophylactic dosing, half-life of 8 hours Metabolism

Hepatic via CYP3A4 Adverse Effects

Hepatotoxicity/hepatitis and photosensitivity (with chronic use)—NO contraindication exists for crisis therapy. Tachycardia, pericarditis, pleural effusion, cramping, diarrhea, weakness, myalgia, drowsiness, dizziness, somnolence, respiratory depression

CLINICAL PEARLS

• Difficult to mix, each vial must be reconstituted with 60 mL sterile water (preservative-free) • Each vial contains 3 g of mannitol, average crisis event requires 30 vials • During an MH crisis, can be administered IV push; subsequent doses should be given over 2– 3 minutes • Reconstituted pH is 9.5; avoid extravasation as it can cause severe tissue damage • Crises therapy includes other supportive measures such as immediate cessation of the triggering agent, 100% oxygen, adequate ventilation, acid–base and electrolyte management, and cooling of the patient • Additive CNS depression may occur. Calcium channel blockers are contraindicated while using dantrolene, as it may cause dysrhythmias or hyperkalemia

ASTHMA/COPD DRUGS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Albuterol (Proventil®, Ventolin®, Pro-Air®) • Metered dose inhaler 2 puffs every 4–6 hours (for acute exacerbation may give 4–8 puffs every 20 minutes for up to 4 hours) • May be administered per endotracheal tube during positive pressure breath with special adapter or attached to the ETCO2 monitoring port • Available for nebulizer delivery • Pediatric doses vary by age • Pregnancy Category: C • Lactation unknown

Mechanism of Action

Relatively specific β2-agonist that increases intracellular cAMP. This causes a decrease in intracellular calcium concentrations, which relaxes bronchial smooth muscle and provides bronchodilation Uses

• Bronchodilator • Hyperkalemia

Onset

• 10 minutes via inhaler/nebulizer; peak effect 0.5–2 hours • 2–3 hours orally

Duration

3–4 hours if inhaled, oral 4–6 hours Metabolism

Hepatic, to inactive sulfate, 30% is excreted unchanged in the urine. No dosage change required in renal failure Adverse Effects

Tachycardia, chest pain, palpitations, arrhythmia, hyper- or hypotension, flushing, anxiety, tremor/CNS stimulation, hypokalemia (via redistribution), hyperglycemia (repeated dosing), paradoxical bronchospasm, hypersensitivity reactions

CLINICAL PEARLS

• Shake inhaler well prior to use • Use with caution in patients with heart disease, arrhythmias, seizure disorders, hyperthyroidism, and hypokalemia (can further reduce serum potassium) • Beta-blockers antagonize action

TREATMENT DRUGS

Albuterol/ipratropium (Combivent®), ipratropium (Atrovent®) • Metered dose inhaler 2 puffs 4 times daily • Nebulized solution 500 mcg 4 times daily • Ipratropium: Pregnancy Category: B, lactation unknown

Mechanism of Action

• See “Albuterol” • Ipratropium is a locally acting anticholinergic agent that decreases intracellular GMP levels, thereby providing additive bronchodilation to albuterol, and reducing bronchial secretions

Uses

COPD, asthma Onset

3–15 minutes, peak response 1–2 hours Duration

4–6 hours

Metabolism

Ester hydrolysis, to several inactive metabolites Adverse Effects

Bitter taste, xerostomia, increased intraocular pressure, urinary retention, bronchitis, paradoxical bronchospasm, upper respiratory traction infection, bronchitis, hypersensitivity reactions

CLINICAL PEARLS

• Shake inhaler well prior to use • Use with caution in patients with glaucoma, bladder outlet obstruction, prostatic hypertrophy • Avoid contact with eyes • Ipratropium is added to albuterol for additional efficacy. Anticholinergic agents may be more effective in patients with COPD

TREATMENT DRUGS

Terbutaline (Brethine®) • Asthma/bronchospasm SC 0.25 mg, may repeat in 15–30 minutes (no more than 0.5 mg in a 4-hour period) • Pediatric—varies by age and weight • For tocolysis, SC 0.25 mg, can repeat in 20 minutes • Pregnancy Category: B • Lactation—enters breast milk, compatible with breastfeeding

Mechanism of Action

Specific β2-agonist that increases intracellular cAMP. This results in a decreased calcium flux into uterine and bronchial cells, producing muscle relaxation Uses

• Asthma • Bronchospasm • Tocolysis (off-labeled use, typically used for <48-hour)

Onset

6–15 minutes subcutaneous dosing, oral 30–45 minutes Duration

Half-life 2–5 hours Metabolism

• Oral dosing: Hepatic, to inactive sulfate metabolite • Subcutaneous dosing: 90% is excreted renally, 60% unchanged. Decrease dosing by 50% for creatinine clearance (CrCl) <50, avoid if CrCl <10

Adverse Effects

Tachycardia, palpitations, flushing, hypertension, anxiety, tremor, restlessness, hypokalemia, hyperglycemia (repeated doses), increased risk of pulmonary edema, fetal tachycardia, paradoxical bronchospasm, hypersensitivity reactions

CLINICAL PEARLS

• Recent (February 2011) FDA Black Box warning for maternal tachycardia, dysrhythmias, hypokalemia, hyperglycemia, pulmonary edema, and myocardial ischemia when used for preterm labor >48 hours. Contraindicated as tocolytic for placental abruption and in preeclamptic patients • Antagonized by nonspecific beta-blockade, less so with selective beta-1-blockers. Use with caution in patients with cardiac disease, seizure disorders, hyperthyroidism, diabetes, and hypokalemia

Table 1 Long-acting beta-agonists

TREATMENT DRUGS

Long-acting beta-agonists (formoterol, salmeterol), combinations with inhaled corticosteroids • Pregnancy Category: C • Lactation—enters breast milk/use caution

Mechanism of Action

Relaxation of bronchial smooth muscle via agonism at β2-receptors

Uses

• Chronic control of asthma • COPD • Exercise-induced asthma

Adverse Effects

Headache, tremor, hypokalemia, tachycardia, hypertension, hyperglycemia, nasal congestion, pharyngitis, cough. Corticosteroid combinations may produce candidiasis of upper airway, dysphonia, and systemic effects

CLINICAL PEARLS

• Not intended for control of acute bronchospasm or acute exacerbations of asthma or COPD • Decreases incidence of acute exacerbation of COPD and improves pulmonary function • Usually added to inhaled corticosteroid therapy if control is inadequate • Tolerance to long-acting β-agonists may occur over time • May increase risk of asthma-related death

TREATMENT DRUGS

Tiotropium (Spiriva®) • Inhalation 18 mcg once daily • Pregnancy Category: C • Breastfeeding unknown

Mechanism of Action

• Inhaled anticholinergic agent that acts as an antagonist at muscarinic receptors in bronchial smooth muscle, thereby producing bronchodilation Uses

Chronic control of COPD Onset

Time to peak 5 minutes Duration

Half-life 5–6 days Metabolism

Minimal hepatic via CYP2D6 and CYP3A4, excreted in urine and feces Adverse Effects

Xerostomia, upper respiratory tract infection, pharyngitis, sinusitis, constipation, urinary retention

CLINICAL PEARLS

• Not intended for acute bronchospasm, acute exacerbation of COPD, or acute asthma attacks • No evidence for tolerance • Decreases incidence of COPE exacerbation • May produce additive effects with other anticholinergic agents

TREATMENT DRUGS

Theophylline

• PO slow release tablets for chronic conditions: 300–600 mg once daily • IV form (aminophylline) 4.6 mg/kg loading dose, then 0.4 mg/kg/hour (based on theophylline content) • Pediatric doses vary by age and weight • Decreased doses required in elderly, in hepatic disease, or with CHF, due to reduced clearance • Pregnancy Category: C • Breast feeding—levels in milk similar to maternal serum levels

Mechanism of Action

• Bronchodilation produced by increased intracellular levels of cAMP, due to inhibition of phosphodiesterase • Also causes CNS and cardiac stimulation, diuresis

Uses

• COPD • Asthma • Uncommonly used for acute exacerbations in IV form

Onset

• 30 minutes IV • 1 hour PO

Duration

Half-life 3–8 hours, highly variable, varies by age, liver/cardiac function, smoking history Metabolism

• Hepatic via multiple CYP isoenzymes, to active metabolites; 50% is excreted unchanged in the urine

Adverse Effects

Nausea, vomiting, nervousness, tremor, headache, insomnia, tachycardia/dysrhythmias, seizures

CLINICAL PEARLS

• Not commonly used due to its narrow therapeutic index, adverse effects, and need for monitoring of serum levels. Adverse effects increase as serum levels exceed 12–15 mcg/mL (usual adult therapeutic levels 5–15 mcg/mL) • Many drug interactions exist • Aminophylline is the ethylene diamine salt of theophylline (theophylline dose is 80% of aminophylline dose)

BETA BLOCKERS

Alan J. Kover, MD, PharmD

TREATMENT Mechanism of Action

• Selective competitive antagonism of beta-adrenergic receptors. They can be categorized as: – Nonselective beta blockade (blocks both beta-1 and beta-2 receptors) – Relatively selective beta-1 blockade – Having alpha-1 blocakde activity

Table 1 Beta blocking agents • Beta blockade produces reduced chronotropy, dromotropy, and inotropy. They decrease myocardial oxygen consumption while increasing myocardial oxygen supply (increase diastolic time and perfusion of the left ventricle). Those with alpha-1 blocking activity also cause vasodilation/reduced SVR (afterload) Uses

• Hypertension • Angina • Congestive heart failure • Tachyarrhythmias • Treatment of acute coronary syndromes/ischemia • Perioperative beta-blockade • Preoperative preparation of hyperthyroid patients • Migraine prophylaxis

Adverse Effects

Bradycardia, heart block, hypotension, bronchospasm, CHF/worsening, increased symptoms of peripheral vascular disease, fatigue, lethargy, potentiation of hypoglycemia, withdrawal hypersensitivity. Orthostasis and edema may occur in patients on combined beta/alphablockers

CLINICAL PEARLS

• Receptor specificity is decreased with increasing doses • Beta-1 selective blockade is preferred in patients with reactive airway disease/bronchospasm, and those with peripheral vascular disease • Caution should be used in hypovolemic patients or those with severe LV dysfunction, and in patients with sick sinus syndrome or 2nd/3rd degree heart block unless a functioning pacemaker is in place • Low doses should be used in patients with chronic CHF • May augment cardiac suppressant effects of volatile anesthetics and calcium channel

blockers • Many drug interactions involve CYP isoenzymes • Should be continued in the perioperative period if patients are taking chronic beta blockade • Initiation of perioperative beta-blockade for prophylactic purposes is controversial

CALCIUM CHANNEL BLOCKERS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Dihydropyridines

Mechanism of Action

• Inhibits calcium entry via voltage-gated calcium channels from the extracellular compartment or sarcoplasmic reticulum. This results in vascular smooth muscle relaxation in coronary and peripheral beds, resulting in: – Lowering the systemic vascular resistance (afterload, blood pressure) – Dilation of coronary vessels, which improves myocardial O2 delivery

– May also decrease cardiac contractility and conductance (less so than nondihydropyridines)

Uses

• Hypertension • Angina (chronic and Prinzmetal’s) • Vasospasm • Raynaud’s disease • Nifedipine may be used for pulmonary hypertension Table 1 Dihydropyridine calcium channel blockers Adverse Effects

Dizziness, hypotension, syncope, headache, fluid retention/edema, reflex tachycardia, palpitations flushing, gingival hyperplasia, fatigue, depression, insomnia, impotence

CLINICAL PEARLS

• Should be continued preoperatively due to the risk of vasospasm upon withdrawal • Potentiation/prolongation of neuromuscular blockade and potentiation of cardiac depressant effects of volatile anesthetics should be anticipated • Caution in patients with LVOT obstruction/aortic stenosis • Many combination products exist with diuretics and other antihypertensives • Many drug interactions exist with drugs metabolized by CYP3A4 and some other cytochromes. Inducers of 3A4 reduce the effectiveness of dihydropyridines (except clevidipine) • Sublingual or immediate release nifedipine is no longer recommended for the treatment of acute hypertension or angina due to the increased incidence of hypotension and cardiac ischemia/infarction

• Nimodipine has a greater effect on cerebral arteries than other dihydropyridines and is indicated only for vasospasm due to subarachnoid hemorrhage • Nicardipine and clevidipine (emulsified in lipid vehicle similar to that is utilized for propofol) are the only IV forms available • Clevidipine is contraindicated in patients with egg/soybean allergies

TREATMENT DRUGS

Non-Dihydropyridine Calcium Channel Blockers Mechanism of Action

• Similar to dihydropyridines – Verapamil is more selective for myocardial depression – Diltiazem has balanced action as a myocardial depressant and vasodilator, with less reflex tachycardia

Uses

– Hypertension – Angina – Supraventricular dysrhythmias – Migraine or cluster headache Table 2 Non-dihydropyridine calcium channel blockers Adverse Effects

Hypotension, bradycardia, CHF, syncope, edema, headache, fatigue, dizziness, constipation, gingival hyperplasia

CLINICAL PEARLS

– Contraindicated in 2nd or 3rd-degree AV block (unless the patient has a functioning pacemaker) WPW Severe LV dysfunction Hypotension Cardiogenic shock – Extreme caution should be exercised in patients already receiving beta-blockers, digoxin, or with LVOT obstruction/aortic stenosis – Should be avoided in patients with CHF – Inhibits the metabolism of benzodiazepines and lower doses should be considered – Augments the activity of neuromuscular blockers, and have additive cardiac depression with volatile anesthetics – Both have some intrinsic local anesthetic activity and increase the risk of local anesthetic toxicity

– Severe hyperkalemia may result if given with dantrolene – Have many drug interactions involving CYP3A4 and other cytochromes

CHEMOTHERAPEUTIC AGENTS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Cyclophosphamide (Cytoxan®) • Usual dose should be adjusted for renal dysfunction, possibly for hepatic dysfunction • Pregnancy Category: D • Breastfeeding: Not recommended

Mechanism of Action

Alkylating agent: Crosslinks DNA, prevents cell division Uses

Antineoplastic agent—leukemias, lymphomas, breast and ovarian cancers, preparation for bone marrow transplant, SLE Onset

Oral time to peak 1 hour Duration

Half-life 3–12 hours Metabolism

• Is a prodrug, must be activated in the liver, to 4 active metabolites • Excreted in urine

Adverse Effects

Cardiotoxicity (especially high doses), CHF, myocarditis, pericarditis, pericardial effusion, immunosuppression, pneumonitis, pulmonary fibrosis, hemorrhagic cystitis, SIADH, pancytopenia, mucositis, stomatitis, alopecia, nausea and vomiting

CLINICAL PEARLS

• May cause tissue injury if extravasated • May inhibit pseudocholinesterase which can last 3–4 weeks after dose given, risk of prolonged effect if succinylcholine administered • May potentiate anthracycline-induced cardiotoxicity • Hydration must be maintained to decrease risk of hemorrhagic cystitis

TREATMENT

DRUGS

Methotrexate (MTX) • Rheumatoid arthritis: PO initially 15 mg/week, with increases of 5 mg/month to 25–30 mg/week • Dose requires adjustment if renal dysfunction is present, possibly if hepatic dysfunction is present • Pregnancy Category: X • Breastfeeding: Contraindicated

Mechanism of Action

• Folate antimetabolite, inhibits DNA synthesis • Has immune modulation and anti-inflammatory activity

Uses

Antineoplastic agent used in breast cancer, head and neck cancers, leukemias, and lymphomas rheumatoid arthritis, severe psoriasis, other autoimmune diseases Onset

3–6 weeks as antirheumatic agent Duration

Dose related half-life, 3–15 hours Metabolism

Converted to 7-hydroxy-MTX, an active metabolite, in hepatic tissue. Intracellularly to polyglutamates, which are as active as parent drug. Excretion via urine and feces Adverse Effects

Acute nephrotoxicity, myelosuppression, immunosuppression, mucositis, stomatitis, hypersensitivity, pneumonitis, pulmonary edema/fibrosis, pleurisy, meningeal irritation, encephalopathy, hepatotoxicity, severe dermatologic toxicity, nausea, vomiting, diarrhea

CLINICAL PEARLS

• NSAIDs reduce excretion of MTX and increase the risk of nephrotoxicity • Chemotherapeutic doses are often followed by leucovorin rescue, which circumvents antifolate activity, meant to decrease toxic effects on normal cells • May also be given intrathecally for meningeal leukemia

TREATMENT DRUGS

5-fluorouracil • No specific changes for hepatic or renal disease

• Pregnancy Category: D • Breastfeeding: Not recommended

Mechanism of Action

Pyrimidine antimetabolite, interferes with DNA synthesis by inhibiting thymidylate synthetase Uses

Antineoplastic agent for colorectal, gastric, esophageal, pancreatic, head and neck, breast, ovarian, renal cell cancer Onset

Biphasic half-life Duration 3 weeks

Metabolism

• Is a prodrug, requires activation • Hepatic, 90% metabolized • Excreted by lungs as CO2 Adverse Effects

Cerebellar dysfunction, multifocal leukoencephalopathy, coronary vasospasm/angina, myelosuppression, mucositis, hand-foot syndrome, rash, nausea, vomiting, diarrhea, alopecia, hypersensitivity reactions

CLINICAL PEARLS

• Is a strong CYP2C9 inhibitor, enhances effects of warfarin • Hand-foot syndrome also known as palmar-plantar erythrodysesthesia, is a result of vasoocclusion of the small vessels in periosteum of metacarpals/metatarsals, resulting in painful acral erosions/bullae in hands/feet • Capecitabine is an orally available agent similar to 5-FU

TREATMENT DRUGS

Bleomycin (Blenoxane®)

• Doses should be adjusted for renal dysfunction • Pregnancy Category: D • Breastfeeding: Not recommended

Mechanism of Action

Inhibits DNA synthesis, causes single- and double-strand breaks in DNA

Uses

Antineoplastic agent for lymphomas, Hodgkin disease, testicular and ovarian cancer, intrapleural administration for malignant effusions Onset

Unavailable Duration

Half-life 9 hours, up to 30 hours in renal failure Metabolism

Metabolized in several tissues, including lung, liver, skin, renal, excreted unchanged in urine Adverse Effects

Pneumonitis, pulmonary interstitial fibrosis, acute pericarditis, acute chest pain syndrome, pulmonary vaso-occlusive disease, acute hypersensitivity reaction, dermatologic reactions, hyperpigmentation, mucositis

CLINICAL PEARLS

• Pulmonary toxicity increases with higher cumulative dose (>400 units), administration of other agents with pulmonary toxicity, older age, and higher administered FiO2. Presents as

a restrictive pulmonary disease. Steroids may have some efficacy for treatment of pulmonary toxicity. Anesthetic management should strive to limit the FiO2 to the lowest

level possible, while keeping oxygen saturation >90%, judicious use of PEEP, and meticulous, conservative fluid management • A small test dose is usually given prior to therapy due to a risk of an acute hypersensitivity reaction • Myelosuppression and vomiting uncommon with this agent

TREATMENT DRUGS

Vinca alkaloids (vincristine, vinblastine, vinorelbine) • Requires adjustment in hepatic dysfunction, based on serum bilirubin levels • Pregnancy Category: D • Breastfeeding: Not recommended

Mechanism of Action

Binds to tubulin, inhibits polymerization of microtubules and arrests mitosis in metaphase Uses

Antineoplastic agent for lymphomas, ALL, brain, breast, testicular, lung cancers

Onset

Unavailable Duration

Vincristine half-life 85 hours, vinblastine 25 hours, vinorelbine 28–44 hours Metabolism

• Hepatic via CYP3A4, excreted primarily in feces • Vinblastine and vinorelbine have an active metabolite

Adverse Effects

Peripheral neuropathy, SIADH, bronchospasm, mental status alteration, ataxia, neuropathic pain, cranial nerve involvement, hepatic veno-occlusive disease, severe constipation. Myelosuppression more of a concern with vinblastine and vinorelbine, but they are less neurotoxic than vincristine

CLINICAL PEARLS

• Presence of peripheral neuropathy may preclude regional anesthesia. May also induce an autonomic neuropathy. Presents as peripheral paresthesias with depression of DTRs, which progress with therapy, may be accompanied by motor weakness • Inadvertent intrathecal administration can cause death • Avoid extravasation, these agents are vesicants • High risk of drug interactions

TREATMENT DRUGS

Taxanes (paclitaxel, docetaxel) • May need dose adjustment if hepatic enzyme elevation is present • Pregnancy Category: D • Breastfeeding: Not recommended

Mechanism of Action

Inhibits cell division by stabilizing tubulin dimers, inhibiting their disassembly and impairing mitosis Uses

Antineoplastic agents, for breast, ovarian, lung, and bladder cancers Onset

Unavailable Duration

• Paclitaxel: Half-life 6–52 hours, longer for prolonged infusion times

• Docetaxel: Half-life 11 hours

Metabolism

Hepatic via CYP2C8 (paclitaxel) and CYP3A4 to metabolites excreted mostly into feces Adverse Effects

Asymptomatic bradycardia, severe brady/tachydysrhythmias, asystole, myocardial ischemia/infarction, hypotension, peripheral edema, peripheral neuropathy, autonomic neuropathy, myelosuppression, hypersensitivity reactions, alopecia, mucositis, nausea and vomiting (less common than with other agents)

CLINICAL PEARLS

• Premedication with corticosteroids and antihistamines (anti H1 and anti H2) are required when giving taxanes due to risk of hypersensitivity reactions • Myelosuppression is the dose limiting toxicity • Cardiotoxicity more common with docetaxel • Risk of peripheral edema increases if given with cisplatinum • Peripheral neuropathy is mostly sensory and may preclude use of regional anesthesia

TREATMENT DRUGS

Platinating agents (cisplatin, carboplatin, oxaliplatin) • Doses should be reduced in renal dysfunction • Pregnancy Category: D • Breastfeeding: Not recommended

Mechanism of Action

Crosslinks/denatures DNA helices, impairs DNA synthesis and function Uses

Antineoplastic agent for ovarian, testicular, bladder, head and neck, other cancers. Oxaliplatin used for colon, GI cancers Duration

Cisplatin terminal half-life 24 hours, secondary half-life 44–73 hours. Carboplatin half-life: 2.6–5.9 hours. Oxaliplatin terminal half-life: 391 hours Metabolism

• Cisplatin—non-enzymatic inactivation by combining with sulfhydryl groups in serum and cells. Carboplatin—minimal hepatic metabolism. Oxaliplatin—non-enzymatic metabolism to active and inactive metabolites • Excreted in urine

Adverse Effects

Peripheral neuropathy, myelosuppression, renal toxicity (dose limiting), hypomagnesemia, hypokalemia, hypersensitivity reactions, ototoxicity, nausea, vomiting, mucositis. Ice, cold temperatures, hypothermia may worsen neuropathy, especially with oxaliplatin

CLINICAL PEARLS

• Pretreatment with IV fluids (normal saline-chloride ion is nephroprotective) and close monitoring of electrolytes are required with cisplatin • Renal and neurotoxicity are decreased with carboplatin and oxaliplatin • Co-administration with aminoglycosides and other nephrotoxins increase the risk of renal toxicity • Peripheral neuropathy is dose and duration related, manifested by paresthesias, loss of DTRs and vibration sense, and ataxia may preclude use of regional anesthesia • May cause tissue damage if extravasated

TREATMENT DRUGS

Anthracyclines (doxorubicin, daunorubicin, idarubicin, epirubicin) • May need adjustment for hepatic disease, neutropenia, or thrombocytopenia • Pregnancy Category: D • Breastfeeding: Not recommended

Mechanism of Action

Intercalates DNA, inhibits replication, and inhibits DNA/RNA polymerases, causing cell death Uses

Antineoplastic agent for leukemias, lymphomas/Hodgkin disease, breast, lung, gastric, and thyroid cancers Onset

Unavailable Duration

Varies by agent Metabolism

Hepatic via CYP2D6 and CYP3A4, to inactive and active metabolites, excreted in feces and urine Adverse Effects

Acute/chronic cardiotoxicity (dose-related)—dysrhythmia, prolonged Qt, conduction abnormalities, cardiomyopathy, CHF, pericarditis, myelosuppression, mucositis, alopecia,

nausea and vomiting, discoloration of urine

CLINICAL PEARLS

• May exhibit additive cardiac depression with anesthetic agents, even if resting cardiac function normal. Cardiotoxicity may manifest a year or more after therapy. For doxorubicin, cardiotoxicity may become irreversible if the total lifetime dose approaches 450–500 mg/m2. Risk factors for cardiotoxicity include extremes of age, previous cardiac disease, concurrent radiation therapy to mediastinum, and concurrent therapy with cyclophosphamide • Causes tissue damage if extravasated • Many drug interactions

CNS ACTING DRUGS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Lithium Carbonate (Lithobid SR® is sustained release product) • PO 900–1,800 mg daily in 3 divided doses, or BID with sustained release product • Dose reduction required in renal dysfunction • Pediatric age >6: 15–60 mg/kg/day • Pregnancy Category: D • Breastfeeding contraindicated

Mechanism of Action

• Exact mechanism is unknown • Alters cation transport across the cell membranes of nerve and muscle cells • Alters reuptake of serotonin and norepinephrine in nerve cells • Reduces sensitivity of certain CNS dopamine receptors

Uses

• Treatment of acute mania in bipolar disorder; mood stabilizer • Chronic pain adjunct

Onset

Time to peak 4–12 hours with extended release product Duration

Half-life 18–24 hours Metabolism

• Primarily excreted in the urine (95%) • Increased sodium intake and osmotic diuretics increase renal excretion (may necessitate increased dosing) Adverse Effects

• Acute intoxication (correlates with serum levels >1.5 mEq/L) usually manifests as vomiting, profuse diarrhea, confusion, hyperreflexia, coma, and seizures. Mild toxicity can usually be managed with supportive measures (sodium and fluid repletion) whereas severe toxicity can require hemodialysis. Co-administration of drugs that increase reabsorption or decrease excretion in the kidneys include NSAIDs, ACE-inhibitors, thiazide diuretics, and metronidazole • Nausea, fatigue, dizziness, tremor, thirst, polyuria, edema, weight gain, confusion, ataxia,

seizures, renal toxicity, nephrogenic diabetes insipidus, hypothyroidism, leukocytosis • Hypothermia may result when co-administered with diazepam • Prolongs effects of neuromuscular blocking drugs • Increases risk of serotonin syndrome if given with other agents that modulate CNS serotonin levels

CLINICAL PEARLS

• Most effective drug for treatment of bipolar disorder • Therapeutic serum levels are 0.6–1.2 mEq/L for acute mania, and 0.8–1.0 mEq/L for chronic maintenance therapy • Careful monitoring of fluid status, electrolytes, and lithium levels are required if the patient needs to maintain use of this drug in the perioperative period Table 1 Atypical antipsychotic agents

TREATMENT DRUGS

Atypical antipsychotic agents Some agents require alteration of dosage in patients with renal or hepatic dysfunction. In general, lower doses are used in the elderly Mechanism of Action

• Antagonists at dopamine-2 receptors in the brain • They also produce some modulation of serotonin receptors

Uses

• Psychoses • Schizophrenia • Agitation • Acute mania • Bipolar disorder • Adjuncts in treatment of depression

Adverse Effects

• Tardive dyskinesia, extrapyramidal muscle movements, hyperglycemia, diabetes, weight gain, hyperlipidemia, impaired temperature regulation, QT interval prolongation/risk of Torsades, elevation of prolactin levels, somnolence, orthostatic hypotension • Lower risk of anticholinergic side effects than older agents

CLINICAL PEARLS

• In general, the newer generation of antipsychotics have the same efficacy as older agents but with a lower incidence of tardive dyskinesia, extrapyramidal muscle movements, and neuroleptic malignant syndrome • The most effective agent is clozapine; however, it is not commonly used due to its ability to cause agranulocytosis, seizures, and myocarditis • Parenteral forms (IM use only) of aripiprazole, olanzapine, and ziprasidone are available • Impaired temperature regulation is a concern intraoperatively • May hold these agents perioperatively (long half-lives) unless there is a high risk of exacerbation of psychiatric disease present • There are many potential drug interactions • There exists an increased risk of death in elderly patients with dementia • If taken during the 3rd trimester of pregnancy, there is an increased risk of EPS and withdrawal symptoms in the newborns

COCAINE

Nabil Elkassabany, MD

TREATMENT DRUGS

• Usual dose: – Topical use 1–10% concentration, applied to desired mucosal area, not to exceed 1 mg/kg – Reduce dose in children and the elderly – Pregnancy class C, X for non-medical use – Breastfeeding contraindicated, excreted in breast milk Mechanism of Action

• Esteratic local anesthetic agent • Blocks voltage-gated sodium channels and inhibits depolarization, initiation, and conduction of nerve impulses • Blocks neuronal reuptake of norepinephrine resulting in CNS stimulation, tachycardia, hypertension, and vasoconstriction • Blocks neuronal reuptake of dopamine and serotonin in the midbrain, with resulting euphoria and arousal Uses

• Local anesthetic with vasoconstrictor activity, used on mucosal surfaces of the respiratory tract for otorhinolaryngology procedures and bronchoscopy • Used in combination with other agents (tetracaine-adrenaline-cocaine) for the repair of minor head and neck lacerations • Commonly abused CNS stimulant in the US (National Institute of Drug Abuse NIDA)

Onset

1 minute when applied to mucosa, peak effect in 5 minutes Duration

Serum half-life of cocaine is 30–90 minutes Metabolism

• Non-enzymatic hydrolysis to benzoylecgonine, via hepatic esterases, or plasma pseudocholinesterases to ecgonine methylester, and minimal amounts by CYP3A4 to norcocaine, all of which are active and excreted in urine • Benzoylecgonine has the highest concentration in urine and can be detected for 2–3 days after exposure Adverse Effects

Hypertension, tachycardia, dysrhythmias, myocardial ischemia, CNS stimulation, euphoria,

hallucinations, paranoia, seizures, fever, agitation, restlessness, tremor, stroke, mydriasis, rhinitis, tachypnea, vasculitis, Raynaud’s phenomenon

CLINICAL PEARLS

• Should not be applied to inflamed or traumatized mucosa • Other vasoconstrictors should not be used within 2 hours of cocaine exposure • Avoid using with other drugs that can result in tachycardia and hypertension, such as pancuronium or ketamine • Caution in use of beta-blockade for treatment in cocaine toxicity, due to risk of unopposed alpha-induced vasoconstriction/ischemia • Concern regarding prolonged action of succinylcholine used simultaneously with cocaine has been refuted in clinical studies • Toxicity has occurred in infants breastfed by cocaine-abusing mothers • Medical use is generally declining, due to adverse effects, abuse liability, and availability of effective alternatives

DIURETICS/COLLOIDS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Furosemide (Lasix®) • Adult IV (or IM) 20–40 mg initially, may repeat or increase dose by 20 mg in 2 hours. IV infusion not to exceed 4 mg/minute may also be used. Single maxi- mum doses of 200 mg may be used, as appropriate • Pediatric IV/IM 1 mg/kg/dose • Pregnancy Category: C, caution with breastfeeding

Mechanism of Action

• Inhibits chloride binding co-transport of sodium and chloride in the ascending loop of Henle and distal renal tubule • Results in sodium, chloride, potassium, calcium, and magnesium excretion in the urine • Increases venous capacitance and decreases cardiac output

Uses

Acute pulmonary edema, CHF, edema. May also be used for hypercalcemia (with saline administration), hyperkalemia, ascites, during renal transplant to invoke diuresis Onset

IV 5 minutes, IM 30 minutes, PO 30–60 minutes Duration

IV 2 hours, PO 6–8 hours Metabolism

Hepatic—minimal. Excretion of unchanged drug 80% renal for parenteral dose, oral dosing 50% renal, 50% fecal Adverse Effects

Hypokalemia, hypomagnesemia, hypotension, hyperglycemia, hyperuricemia, volume depletion, metabolic alkalosis, ototoxicity (especially if >4 mg/minute IV administered)

CLINICAL PEARLS

• Other loop diuretics (with dose equivalents to furosemide 40 mg) include bumetanide 1 mg, torsemide 10 mg, and ethacrynic acid 50 mg • Close monitoring of renal function and electrolytes is required • Caution with use in patients with an allergy to sulfonamides

• If used for the treatment of ascites in cirrhotics, should be carefully dosed and monitored to avoid severe hypokalemia and intravascular volume depletion Table 1

TREATMENT DRUGS

Hydrochlorothiazide (HCTZ)

• Adult PO 12.5–100 mg/daily • Pediatric PO 1–3 mg/kg/day • Pregnancy Category: B; breastfeeding not recommended

Mechanism of Action

• Inhibits sodium reabsorption in distal tubule of the nephron, causing increased excretion of sodium and water, as well as hydrogen and potassium ions

Uses

Diuresis, hypertension, edema Onset

2 hours, peak effect 4–6 hours Duration

6–12 hours

Metabolism

Into urine, unchanged Adverse Effects

Dehydration, hypovolemia, hypotension, hyponatremia, hypochloremic hypokalemia, hypomagnesemia, hyperuricemia, hyperglycemia, hypercalcemia

CLINICAL PEARLS

alkalosis,

• Component in many antihypertensive drug combinations, given to counteract fluid/sodium retention induced by other agents • Ineffective at CrCl <30 mL/minute unless combined with a loop diuretic • Caution in patients with true allergy to sulfas, though cross-sensitivity uncommon • Usually held on the day of surgery due to its volume depleting and electrolyte effects

TREATMENT DRUGS

Potassium-sparing diuretics

Mechanism of Action

• Spironolactone/eplerenone act as aldosterone antagonists at the distal renal tubule, thereby causing sodium and water diuresis, conservation of potassium and hydrogen ion • Triamterene and amiloride: Inhibit Na+/K+ ATPase in the distal tubule, causing sodium loss and potassium retention Uses

Hypertension, edema. Aldosterone antagonists as adjunct in treatment of chronic CHF. Spironolactone used for acne/hirsutism in women Adverse Effects

Hyperkalemia, hyponatremia, hypovolemia, dizziness, fatigue, nausea, metabolic acidosis. Spironolactone (also eplerenone to lesser extent) have antiandrogen effects, may produce gynecomastia and erectile dysfunction in men, menstrual irregularities in women

CLINICAL PEARLS

• Hyperkalemia is more common in patients taking ACE inhibitors, angiotensin receptor blockers (ARBs), or dietary/supplementary potassium • Potassium-sparing agents should be avoided in patients with creatinine clearance <30 mL/minute or serum creatinine ≥2 mg/dL, or if serum potassium >5 mEq/L • Dose should be held on the day of surgery; however, triamterene may cause a rebound potassium diuresis when abruptly discontinued • Caution with use in hepatic disease • All are relatively weak diuretics

TREATMENT DRUGS

Mannitol (Osmitrol®) • Increased intracranial pressure (adult/pediatric): IV 0.25 g/kg/dose, up to 1 g/kg/dose, administered over 20–30 minutes, may be repeated every 6–8 hours with to a goal serum osmolality of 300–320 mOsm/L • Increased intraocular pressure (adult/pediatric): IV 1–2 g/kg over 30 minutes • Pregnancy Category: C, breastfeeding unknown

Mechanism of Action

• Creates an osmotic gradient between the vascular space and brain/eye tissue, facilitating water transfer to the vasculature thereby decreasing intracranial and intraocular pressure • Reflex cerebral vasoconstriction secondary to autoregulation occurs in response to decreased blood viscosity and increased flow to the brain (further decreasing ICP)

Uses

Treatment of increased intracranial or intraocular pressure, initial treatment in severe

traumatic brain injury, renal protection in renal transplant surgery, maintenance of urine flow for pigment-induced nephropathy Onset

For decrease in ICP 15–30 minutes, for diuresis 1–3 hours Duration

ICP reduction for 1.5–6 hours Metabolism

Minimal hepatic metabolism to glycogen, excreted in urine as predominately unchanged drug Adverse Effects

Hyponatremia, hypokalemia, marked diuresis, nausea, headache, dizziness, transient hypotension, pulmonary edema/CHF if rapid volume expansion occurs, subsequent volume depletion

CLINICAL PEARLS

• Contraindicated in patients with severe renal insufficiency • Acts as a vesicant if extravasated due to high osmolality • Closely monitor electrolytes, urine output, volume status • May cause cerebral edema/increased ICP in patients with blood-brain-barrier disruption. May also be intentionally used to disrupt the BBB and allow certain drugs (e.g., chemotherapy agents) to have access to the brain parenchyma

TREATMENT DRUGS

Hetastarch hydroxyethyl starch (Hextend®, Hespan®) • IV 500–1000 mL/day. Doses should not exceed 1,500 mL/day or 25% of the blood volume • In patients with renal insufficiency, reduce subsequent doses by 20–50% • Pregnancy Category: C; breastfeeding unknow

Mechanism of Action

• Colloid that acts as an oncotic agent retains water in the intravascular space

Uses

Volume replacement for hypovolemia, leukapheresis Onset

Volume expansion 30 minutes Duration

24–48 hours

Metabolism

Excreted unchanged via glomerular filtration Adverse Effects

Potential for volume overload/pulmonary edema/CHF, coagulopathy, pruritus, urticaria, anaphylactic/anaphylactoid reactions, hepatotoxicity in prolonged use

CLINICAL PEARLS

• Hextend product is 6% hetastarch solution in lactated Ringer’s; Hespan is 6% hetastarch in 0.9% normal saline • Potential for allergic reactions in patients allergic to corn-based products • Risk of coagulopathy increases when doses exceed 1,500 mL or 25% of blood volume. Results from inhibition of factor VIII/von Willebrand’s factor, impairment of platelet function and hemodilution (prolongs PT and PTT). Should not be given to patients with preexisting coagulopathy

TREATMENT DRUGS

Dextran (Dextran 40, Dextran 70) • Volume expansion IV 500–1,000 mL, given 20–40 mL/minute, max 20 mL/kg/day • DVT/PE prophylaxis IV 50–100 g/day • Pediatric dose Dextran 40: IV 10 mL/day • Pregnancy Category: C, breastfeeding unknown

Mechanism of Action

Volume expander, increases intravascular oncotic pressure Uses

Volume expansion, priming of extracorporeal pump, IV prophylaxis for DVT/pulmonary embolus, distension of uterus during hysteroscopy (Hyskon®)

Onset

Minutes to 1 hour, dependent on molecular weight Duration 24 hours

Metabolism

Excreted unchanged by glomerular filtration, small amount metabolized Adverse Effects

Anaphylaxis/anaphylactoid reactions (more common with dextran 70), fluid overload, pulmonary edema/CHF, coagulopathy, thrombocytopenia

CLINICAL PEARLS

• Use with caution in hepatic or renal dysfunction • Dextran 40 is also referred to as low molecular weight dextran • Depending on the product, may be dispersed in 5% dextrose or normal saline • Caution with use in patients with allergies to corn/corn-derived products. Contraindicated in patients with severe renal insufficiency • May interfere with blood cross-matching

TREATMENT DRUGS

Albumin

• Volume replacement IV 25 g, may repeat in 15–30 minutes if inadequate response, but should not exceed 250 g in a 48–hour period • Volume replacement following paracentesis: IV 5–8 grams of 25% albumin per liter of fluid that is removed • Pediatric IV 0.5–1 g/kg/dose • Pregnancy category: C, compatible with breastfeeding

Mechanism of Action

Increases intravascular oncotic pressure, expands intravascular volume Uses

Volume expansion/treatment of hypovolemia and shock syndromes, acute burn management, treatment of hypoalbuminemia, post-paracentesis fluid resuscitation Duration

16–24 hours for volume expansion. Half-life is around 20 days Metabolism

Multiple sites of catabolism Adverse Effects

Volume overload, azotemia, volume overload, pulmonary edema/CHF

CLINICAL PEARLS

• Prepared as a 5% (osmotically equivalent to plasma) or 25% (five times as osmotically active as plasma) solution; isotonic with plasma • A blood product, so religious considerations exist • May precipitate encephalopathy in hepatic failure or azotemia in renal failure • Unlike starch derived products, has no effect on bleeding/coagulation • More expensive than alternative volume expanders • May expand extravascular spaces if capillaries are not intact (e.g., sepsis)

DYES

Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Methylene blue

• Adult/pediatric methemoglobinemia: IV 1–2 mg/kg or 25–50 mg/m2 over 5–10 minutes; do not dilute • Pregnancy Category: C • Breastfeeding: unknown Mechanism of Action

• Facilitates conversion of methemoglobin to hemoglobin • Forms cyanmethemoglobin in cyanide poisoning that prevents cyanide action on cytochromes in mitochondria • Colors urine and feces blue-green for detection of leakage

Uses

• Treatment of methemoglobinemia • Antidote for cyanide poisoning • Indicator/diagnostic dye

Onset

30–60 minutes Duration

Not specified Metabolism

Reduced to leucomethylene blue, excreted in urine, bile and feces. Caution should be used in severe renal failure Adverse Effects

Hemolytic anemia, dizziness, headache, confusion, diaphoresis, hyper- or hypotension. High doses may cause paradoxical methemoglobinemia

CLINICAL PEARLS

• Serotonin syndrome may be precipitated by the use of methylene blue in patients using serotonin-specific reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and MAOIs (the chemical structure of methylene blue is similar to MAOIs) • May cause paradoxical methemoglobinemia in patients with G6PDH deficiency

• Pulse oximetry is not an accurate measure of oxygenation when methemoglobin concentration increases to 35% or above, requires co-oximetry for accurate measurement • Do not use intrathecally

TREATMENT DRUGS

Indigo carmine • Ampule contains 8 mg indigo carmine/5 mL • Usual dose: IV 5 mL (preferred), may be given IM • Pediatric dose is preferably <5 mL • Pregnancy Category: C • Breastfeeding: unknown

Mechanism of Action

• Indicator dye excreted in urine • Exhibits some alpha-agonist activity

Uses

Localization of ureteral orifices during cystoscopy or ureteral catheterization, diagnostic agent Onset

Blue-colored urine occurs within 10 minutes of IV injection Duration

Half-life 5–10 minutes Metabolism

Excreted in urine Adverse Effects

Bradycardia, AV block, hypo- or hypertension, bronchospasm, idiosyncratic/hypersensitivity reactions, urticaria

CLINICAL PEARLS

• Check ampule for discoloration or precipitation prior to administering, if present, discard • Do not dilute or mix with other solutions, will cause precipitation • Caution in hypertensive patients

ELECTROLYTES

Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Magnesium sulfate • Dose conversion: 1 g magnesium sulfate = 98.6 mg elemental magnesium = 8.12 mEq • Preeclampsia IV 4–6 g over 15–20 minutes, then 1–4 g/hour infusion • Severe or symptomatic hypomagnesemia IV 1–2 g over 5–60 minutes, then 0.5–1 g/hour infusion • Torsades de pointes/polymorphic ventricular tachycardia, or pulseless VT/VF associated with torsades IV 1–2 g push (per ACLS protocol 2010) • Magnesium may also be given IM but severe pain at injection site may occur • PALS dosing IV/IO 25–50 mg/kg/dose • Pregnancy Category: A/C • Breastfeeding: Compatible

Mechanism of Action

• Decreases acetylcholine release at nerve terminals • Blocks calcium entry into smooth muscle thereby inhibiting contraction • Decreases excitatory glutamate-mediated transmission at NMDA receptors in the CNS • Modulates slow inward calcium flux in cardiac cells

Uses

• Preeclampsia/prevention of seizure • Treatment of hypomagnesemia • Arrhythmias: Torsades de Pointes/polymorphic ventricular tachycardia, pulseless VT/VF

Onset

Immediate if given IV for convulsant activity or indicated dysrhythmias Duration

Single IV dose 30 minutes Metabolism

Excreted via glomerular filtration, much is reabsorbed in proximal tubule Adverse Effects

Flushing, vasodilation, hypotension, diaphoresis, electrolyte disturbances, nausea, diarrhea, respiratory depression or cardiac arrest (at higher serum levels). Contraindicated/caution in patients with cardiac conduction blocks

CLINICAL PEARLS

• Serum magnesium levels are an inaccurate measure of the actual intracellular concentration and a poor indicator of repletion during supplementation • Should be used with caution in patients with renal insufficiency or neuromuscular diseases or myasthenia gravis • Hypokalemia commonly accompanies hypomagnesemia, and should be corrected concurrently (note: serum levels of potassium are also an inaccurate measure of actual intracellular concentrations) • Increases sensitivity to non-depolarizing neuromuscular blockers and calcium channel blockers (e.g., treatment of preeclampsia followed by a Cesarean section under general anesthesia) • May enhance the effects of CNS depressants • Administration of magnesium – Therapeutic serum levels are generally 4–7 mEq/L (normal serum levels: 1.4–2.2 mEq/L, varies per lab) and must be monitored – Deep tendon reflexes decrease prior to respiratory depression or cardiac arrest, and can be performed non-invasively and quickly – ECG, blood pressure, pulse oximetry, renal function, and uterine activity (if giving for preeclampsia) should be monitored – IV calcium salts may be given for magnesium toxicity

TREATMENT DRUGS

Sodium bicarbonate • Adult and pediatric in cardiac arrest: IV 1 mEq/kg/dose • Hyperkalemia (adult): IV 50 mEq over 5 minutes – Metabolic acidosis: Dose based on the following formula: – Bicarbonate (in mEq) = 0.2 × weight (kg) × base deficit (mEq/L) – Half of the resulting dose is given immediately, then the rest over 24 hours while monitoring lab values • Pregnancy Category: C • Breastfeeding: Compatible

Mechanism of Action

• Dissociates to provide bicarbonate ion for neutralization of hydrogen ion in blood and urine • Increases in serum pH facilitate potassium being shifted intracellularly

Uses

• Severe metabolic acidosis (controversial) • Hyperkalemia (immediate shifting to the intracellular compartment; does not reduce total body potassium) • Urine alkalinization for treatment of aspirin or tricyclic antidepressant overdose

• Used in ACLS management if cardiac arrest is associated with the above • May help provide renal protection against contrast-induced nephropathy and prevent myoglobin-induced renal damage in rhabdomyolysis • Used as an antacid • May be used to alkalinize local anesthetics to hasten onset time

Onset

IV 15 minutes Duration

IV 1–2 hours Metabolism

• Produces carbon dioxide that is eliminated via ventilation • The kidneys regulate metabolic acid–base balance via filtration/secretion

Adverse Effects

Paradoxical intracellular/CNS acidosis, severe tissue damage if extravasated, edema, pulmonary edema, CHF, hypernatremia, hyperosmolality, hypokalemia, hypocalcemia, metabolic alkalosis

CLINICAL PEARLS

• Routine use in cardiac arrest is not recommended per ACLS guidelines. Administration should be guided by ABGs. Can be considered in prolonged arrest after adequate ventilation has been attained and chest compressions are being performed • Use in metabolic acidosis should occur only after its cause is addressed and pH <7.1 (controversial) • Caution should be exercised in patients who will not tolerate a high sodium load (as in pulmonary edema, CHF, liver failure, etc.) • Changes in blood and urine pH (alkalinization) will affect pharmacokinetics of many drugs; this is sometimes used therapeutically (e.g., excretion of toxins in the urine) • Oxygen delivery to cells may decrease due to a leftward shift of the oxyhemoglobin dissociation curve • Alkalinization of local anesthetics varies by agent; it should not be used with ropivacaine. Typically 1 mL of 8.4% bicarbonate can be used with 10 mL lidocaine

TREATMENT DRUGS

Calcium (chloride and gluconate)

• Usual dose: IV 500–1,000 mg, repeated as necessary (5–10 mL of the 10% calcium chloride solution) • Pediatric IV 20 mg/kg/dose • Pregnancy Category: C

Mechanism of Action

Regulation of nerve and muscle electrical transmission via action potential threshold modulation Uses

• Acute/symptomatic hypocalcemia • Hyperkalemia (>6.5 mEq) • Hypermagnesemia, including associated dysrhythmias

Onset

Given IV, serum levels increase almost immediately Duration

30 minutes to 2 hours per dose IV Metabolism

• Mostly excreted via fecal route from bile and pancreatic secretions • Doses may need to be reduced in patients with renal insufficiency (CrCl <25 mL/minute)

Adverse Effects

Hypotension, vasodilation, cardiac arrest, hypercalcemia, paresthesias, syncope

CLINICAL PEARLS

• 1 g of calcium chloride contains 270 mg of calcium (13.6 mEq) • 1 g of calcium gluconate contains 90 mg of calcium (4.65 mEq) • Avoid extravasation into tissue • Not recommended for routine use in cardiac arrest (unless associated with severe hyperkalemia, hypermagnesemia, hypocalcemia), or in digoxin toxicity • Hypocalcemia may manifest as a prolonged QT interval on ECG, and with skeletal muscle spasm/tetany • Calcium replacement. – Corrected serum levels should be used when the serum albumin is low and can be calculated as follows: Corrected serum calcium = total calcium + 0.8 (4.0 − serum albumin) – Ionized and total calcium levels should be measured, as well as serum phosphate (which may lower serum calcium) – Chloride salt is most commonly used when indicated in cardiac arrest – Unlabeled uses include calcium channel blocker or beta-blocker overdose – Many IV incompatibilities exist

TREATMENT DRUGS

Phosphorous

• Severe symptomatic hypophosphatemia: IV infusion of 0.08–0.16 mmol/kg over 6 hours, either as sodium phosphate or potassium phosphate (15 mmol/250 mL D5W). Levels should be checked after the initial infusion and repeat doses can be given if serum phosphate concentrations remain below 1.5 mg/dL • Mild asymptomatic hypophosphatemia can be treated with oral supplementation: NeutraPhos (250 mg elemental phosphorus, 7 mEq sodium, and 7 mEq potassium per capsule) or Neutra-Phos K (250 mg elemental phosphorus and 14 mEq potassium per capsule)

Mechanism of Action

• Within the body, phosphorus – Stores and releases energy through high-energy bonds (e.g., ATP and creatine phosphate) – Functions as an essential component of the second-messenger systems such as cAMP – Is a major component of nucleic acids, cell membranes, and phospholipids – Promotes release of oxygen from hemoglobin as part of 2,3-diphosphoglycerate

Uses

• Treatment of hypophosphatemia (serum value <2.7 mg/dL) that can result from reduced gastrointestinal uptake, increased renal excretion, or transcellular shifts. In the perioperative setting, acute respiratory alkalosis, malabsorption, refeeding after malnutrition, and alcohol abuse are common causes

Onset

Given IV, serum levels increase almost immediately Metabolism

Excreted in the gastrointestinal tract and in the urine. Once in the kidneys, phosphate is filtered by the glomerulus and reabsorbed in the proximal tubule by passive cotransport with sodium

CLINICAL PEARLS

• Approximately 90% of phosphate in the body is stored in bone • Normal serum phosphorus levels range from 2.7–4.5 mg/dL

ESTERATIC LOCAL ANESTHETICS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Procaine (Novacaine®) • Reduce doses in patients with hepatic impairment or in the elderly • Pregnancy Category: C • Breastfeeding unknown (use caution)

Mechanism of Action

• Reversibly blocks fast voltage gated sodium channels, thus interfering with the conduction of nerve action potentials. Does not change or alter the membrane resting potential • Produces local vasodilation

Uses

Spinal or infiltrative anesthesia Onset

Fast (minutes) Duration

30–60 minutes Metabolism

• Rapid, via plasma cholinesterase (pseudocholinesterase) and subsequently excreted in the urine • Pseudocholinesterase inhibitors decrease local anesthetic metabolism • Less likely to cause systemic toxicity than amides, due to its quicker clearance (the rate limiting step of amide metabolism is hepatic blood flow) Adverse Effects

• Allergic reactions are rare and related to para-aminobenzoate • Neurotoxicity—anxiety, restlessness, disorientation, twitching, confusion, visual disturbance, numbness/paresthesias of lips/mouth, seizures, metallic taste, respiratory arrest • Cardiovascular toxicity—myocardial depression, decreased cardiac output, hypotension, heart blocks, bradycardia, asystole, ventricular dysrhythmias, cardiac arrest • Continuous intra-articular injection may result in chondrolysis

CLINICAL PEARLS

• Para-aminobenzoate metabolite is implicated as the antigen responsible in allergic reactions.

If a true allergy exists, cross-sensitivity with other esteratic local anesthetics is likely. Most purportedly allergic reactions are true allergies to preservatives, or can be attributed to the added epinephrine • Local vasodilation may be antagonized by addition of epinephrine to the injection, which decreases the rate of absorption, serum levels, and risk of local anesthetic toxicity • Adverse effects are generally related to serum levels of local anesthetic, and are usually due to intravascular injection or rapid absorption; this may be less likely with esteratic local anesthetics due to their rapid metabolism. In general, neurotoxicity usually occurs at lower serum levels than cardiac toxicity. Resuscitation in severe cardiac toxicity may be facilitated by IV fat emulsion (Intralipid®)—refer to www.lipidrescue.org and ACLS protocol • Preservative-free preparations are required for neuraxial anesthesia

TREATMENT DRUGS

Chloroprocaine (Nesacaine®) • Toxicity: 11 mg/kg, with epinephrine 14 mg/kg • Doses may require reduction in hepatic impairment and in the elderly • Pregnancy Category: C • Breastfeeding is unknown; therefore use caution

Mechanism of Action See “Procaine” Uses

• Infiltration • Peripheral nerve blocks • Spinal or epidural anesthesia

Onset

Fast (minutes) Duration

30–60 minutes Metabolism

See “Procaine”

Adverse Effects See “Procaine”

CLINICAL PEARLS

• When administered intrathecally with morphine, may interfere with its analgesic effect • Although it has a high pKa, chloroprocaine has a quick onset due to its high concentration

(a large percentage is ionized, but there is more total drug available) • It is formulated as an acidic solution (pH 3.1), thus the addition of 1 mL of NaHCO3 to 30 mL of chloroprocaine may quicken the onset

TREATMENT DRUGS

Tetracaine

Usual dose: Single dose maximum 20 mg. Pregnancy risk C, breastfeeding-unknown/use caution. Mechanism of Action See “Procaine” Uses

Spinal anesthesia Onset Fast

Duration

Spinal 120–360 minutes Metabolism

See “Procaine.” Metabolism slower than for procaine Adverse Effects See “Procaine”

CLINICAL PEARLS See “Procaine”

TREATMENT DRUGS

Benzocaine Usual dose: 200–300 mg

• Should not be used in children less than age 2 • Pregnancy Category: C • Breastfeeding unknown; caution is advised

Mechanism of Action

See “Procaine” Uses

Topical/mucosal anesthesia, used for preparation of airway for endoscopy/fiberoptic intubation Onset

Rapid (minutes) Duration

30–60 minutes Metabolism

• See “Procaine” • Some hepatic clearance

Adverse Effects

• Risk of methemoglobinemia for doses exceeding 300 mg • Local irritation, burning, rash, pruritus, edema, erythema

CLINICAL PEARLS

• Methylene blue is used for treatment of methemoglobinemia. The initial dose is 1–2 mg/kg IV, up to a total of 7–8 mg/kg. • It is a component of several OTC topical anesthetic products, especially for oral mucosal use

H2 BLOCKERS AND NON-PARTICULATE ANTACIDS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Famotidine (Pepcid®) • PO 10 mg once daily up to 40 mg twice daily • IV 20 mg twice daily • Pediatric—varies by age, weight, and indication • Pregnancy risk B, breastfeeding not recommended

Mechanism of Action

• Competitive antagonist of histamine at H2 receptors on gastric parietal cells. Decreases baseline parietal cell acid and volume secretion and blunts the response to normal stimuli • Decreases in gastric acidity and volume inactivate pepsin (inactive form is a bile-chelator) and stimulate gastrin release (increases LES pressure and gastric motility) Uses

• Peptic ulcer disease, gastroesophageal reflux disease, esophagitis, stress ulcer prophylaxis, GI bleeding treatment and prophylaxis, NSAID-induced gastropathy • Urticaria • GI prophylaxis for surgery • Pretreatment prophylaxis for allergic reactions (with H1 blockers and corticosteroids)

Onset

80–90 minutes PO and IV Duration

7–12 hours

Metabolism

• Extensive first-pass metabolism orally; no active metabolites. Renal elimination predominates • May need to decrease dose by 50% for renal insufficiency. No change in dose required for hepatic disease Adverse Effects

Diarrhea, constipation, dizziness, headache, fatigue, muscle pain, cholestatic hepatitis, bradycardia. Rebound gastric acid hypersecretion may occur after discontinuing drug

CLINICAL PEARLS

• May be used evening before or morning of surgery for GI prophylaxis • Acceptable alternative in patients on clopidogrel • May increase risk of pneumonia in susceptible patients • May alter absorption of drugs requiring acid for optimum absorption • Most potent H2 blocker available

TREATMENT DRUGS

Ranitidine (Zantac®) • PO 150 mg once or twice daily, oral liquid available • IV 50 mg every 6–8 hours or 6.25 mg/hour continuous infusion • Pediatric—varies by indication • Pregnancy risk B, breastfeeding use caution

Mechanism of Action

• Competitive antagonist of histamine at H2 receptors on gastric parietal cells. Decreases baseline parietal cell acid and volume secretion and blunts the response to normal stimuli • Decreases in gastric acidity and volume inactivate pepsin (inactive form is a bile-chelator) and stimulate gastrin release (increases LES pressure and gastric motility)

Uses

• Peptic ulcer disease, gastroesophageal reflux disease, esophagitis, stress ulcer prophylaxis, NSAID-induced gastropathy, GI bleeding treatment and prophylaxis, GI prophylaxis for surgery • Pretreatment prophylaxis for allergic reactions (with H1 blockers and corticosteroids) • Urticaria

Onset

1 hour

Duration

4–12 hours

Metabolism

• Renal excretion predominates; it is both filtered and secreted by the renal tubule. Doses should be decreased by 50% in patients with a creatinine clearance <30 mL/minute • Hepatic metabolism occurs via a minor pathway, no active metabolites

Adverse Effects

Headache, fatigue, dizziness, nausea, abdominal pain, diarrhea, constipation, rebound hypersecretion of acid upon discontinuing drug, cholestatic hepatitis, uncommonly bradycardia

CLINICAL PEARLS

• May be used evening before and morning of surgery for GI prophylaxis • Acceptable alternative for patients taking clopidogrel • May increase risk of pneumonia in susceptible patients. • May alter absorption of drugs requiring acid for absorption. Some tablets contain phenylalanine

TREATMENT DRUGS

Nizatidine (Axid®) • PO 150 mg twice daily or 300 mg once daily. • Pediatric
Mechanism of Action

• Competitive antagonist of histamine at H2 receptors on gastric parietal cells. Decreases baseline parietal cell acid and volume secretion and blunts the response to normal stimuli • Decreases in gastric acidity and volume inactivate pepsin (inactive form is a bile-chelator) and stimulate gastrin release (increases LES pressure and gastric motility)

Uses

Peptic ulcer disease, heartburn, gastroesophageal reflux disease Onset

Rapid

Duration

Up to 12 hours Metabolism

• Renal elimination 90% (filtered and secreted), hepatic metabolism (10%) to an active metabolite excreted renally • Dosage reduction (50%) and/or frequency reduction (every other day or 3rd day) required in renal insufficiency. No changes needed for hepatic disease

Adverse Effects

Diarrhea, vomiting, hepatotoxicity, fever, headache, irritability, chest pain, bradycardia, cough, nasal congestion, rhinitis

CLINICAL PEARLS

• Relatively high incidence of headache, upper respiratory complaints and fever more

common in children • Hepatotoxicity may be higher with this agent compared to other H2 blockers • May alter absorption of drugs requiring acid for absorption, and increase incidence of pneumonia in susceptible patients

TREATMENT DRUGS

Cimetidine (Tagamet®) • PO 1,200–1,600 mg daily in divided doses 3–4 times daily • Oral liquid available, parenteral doses similar, can be given IV or IM. • Pediatric 20–40 mg/kg/day in divided doses every 6 hours

Mechanism of Action

• Competitive antagonist of histamine at H2 receptors on gastric parietal cells. Decreases baseline parietal cell acid and volume secretion and blunts the response to normal stimuli • Decreases in gastric acidity and volume inactivate pepsin (inactive form is a bile-chelator) and stimulate gastrin release (increases LES pressure and gastric motility) Uses

• Peptic ulcer disease, gastroesophageal reflux disease, prophylaxis and treatment of upper GI hemorrhage, stress ulcer prophylaxis • Pretreatment prophylaxis for allergic or anaphylactoid reactions (along with H1 blockers and corticosteroids) Onset

15–60 minutes Duration

4–8 hours

Metabolism

• Hepatic metabolism is extensive and occurs via multiple cytochromes to inactivate metabolites that are then excreted by the kidneys • Renal filtration and secretion are also responsible for clearance

Adverse Effects

Diarrhea, altered taste, bradycardia, gynecomastia, impotence, headache, dizziness, somnolence

CLINICAL PEARLS

• Elderly patients on high doses and patients with hepatic or renal disease are especially at risk for reversible confusional states with chronic use • May increase risk of pneumonia in susceptible patients

• Cimetidine is a CYP1A2, CYP2C19, and CYP3A4 inhibitor and alters metabolism of many drugs, including some benzodiazepines, clopidogrel, beta-blockers, calcium channel blockers, antidepressants, meperidine, morphine, and warfarin • Co-administration of cimetidine and dofetilide is contraindicated

TREATMENT DRUGS

Sodium citrate, sodium citrate with citric acid, and sodium citrate with potassium citrate and citric acid • Aspiration prophylaxis: 30 mL PO • Pregnancy risk unknown, breastfeeding compatible

Mechanism of Action

Inorganic salts that immediately bind hydrogen ion in the stomach to increase pH Uses

• Premedication for aspiration prophylaxis, especially when there is an immediate need to increase gastric pH (emergency surgery or Cesarean section) • Also utilized for induction of alkaline diuresis, systemic alkalinization, and hyperphosphatemia of renal disease

Onset

Almost immediate, depends on gastric volume and motility, mixing of contents Duration

Dependent on gastric emptying time Metabolism

Renal excretion of absorbed electrolytes, citrate converted to bicarbonate in liver Adverse Effects

• Chronic alkalinization of gastric fluid (increased susceptibility to acid-sensitive bacilli), urine alkalinization (predisposes to UTIs, urolithiasis), acid rebound, milk-alkali syndrome (ingestion of elemental calcium >2 g may result in calcification within the renal parenchyma with accompanying dysfunction; manifests as increased BUN/Cr, systemic alkalosis, bicarbonaturia, subsequent hypovolemia), and phosphorus depletion can occur with chronic use (unlikely with single doses used for GI prophylaxis). The increase in gastric volume (distension) and salt water taste can induce emesis in some patients

CLINICAL PEARLS

Antacids are categorized as particulate and non-particulate. Particulates (aluminum, magnesium, calcium), if aspirated, may cause a chemical pneumonitis. Non particulates (described above) are clear and if aspirated, cause less foreign body reaction. Mixing is more

complete and rapid than particulate antacids

TREATMENT DRUGS

Sucralfate (Carafate®) • Usual dose: 1 g tablet orally or liquid via gastric tube 2–4 times daily • Pediatric 40–80 mg/kg/day divided every 6 hours • Pregnancy risk B, breastfeeding use caution

Mechanism of Action

Forms a protective barrier in the stomach against acid and pepsin by binding to ulcer adherent exudates and to normal mucosa to some extent Uses

Peptic ulcer disease, stress ulcer prophylaxis, upper GI bleeding prophylaxis, prevention of pneumonia in susceptible patients Onset

1 hour

Duration 6 hours

Metabolism

• Fecal excretion, small amounts via kidney • Little absorption • No need for dosage adjustments in hepatic or renal disease

Adverse Effects

Possible aluminum toxicity in patients with chronic renal failure, constipation

CLINICAL PEARLS

• Alternative for stress ulcer prophylaxis when risk of pneumonia is high • Avoid administration of antacids within 30 minutes of sucralfate • Enteral administration of fluoroquinolone antibiotics with sucralfate results in reduced absorption of the antibiotic; if it is necessary to administer, the fluoroquinolone should be given at least 2 hours before or 6 hours after the sucralfate dose • Digoxin and warfarin absorption are also decreased

HMG COA REDUCTASE INHIBITORS (STATINS) Alan J. Kover, MD, PharmD

TREATMENT DRUGS

• Pregnancy risk X • Breastfeeding not recommended

Mechanism of Action

• Competitive inhibition of HMG-CoA reductase, the rate limiting step in synthesis of cholesterol, also increases clearance of LDL, VLDL • Pleiotropic effects on blood vessels unknown, but have anti-inflammatory effects that include improved vascular endothelial function, atheromatous plaque stabilization, immunomodulation, and decreased thrombogenesis Table 1 HMG CoA reductase Uses

• Treatment of hyperlipidemia • Primary and secondary prevention of cardiovascular events in patients with or high risk of CAD • Reduction of mortality in ACS

Adverse Effects

Myalgia, myopathy, cramps, GI upset, fatigue, hepatotoxicity, transaminase elevation, rhabdomyolysis, rash

CLINICAL PEARLS

• Rhabdomyolysis more common when combined with fibrates, or administering with other CYP3A4 inhibitors (e.g., amiodarone, verapamil, macrolides, protease inhibitors, cyclosporine) • Statins should be continued in the perioperative period in patients taking them chronically, or begun in patients undergoing cardiac/vascular procedures. Cardiac/vascular morbidity/mortality is associated with drug withdrawal in perioperative period • Perioperative use for prophylaxis in other types of surgeries yet to be defined • Possible use in VTE prophylaxis or sepsis controversial/yet to be defined • Caution in patients with active liver disease or ethanol use • Liver enzymes and CPK should be monitored

TREATMENT

DRUGS

IV fat emulsion (Intralipid®) • Local anesthetic toxicity: IV bolus: 1.5 mL/kg lean body weight, infused over 1 minute, then 0.25 mL/kg/minute infusion, with chest compressions per ACLS protocol. May re-bolus 1–2 times for persistent asystole or ventricular fibrillation, and increase infusion to 0.5 mL/kg/minute • Pregnancy risk C • Breastfeeding unknown

Mechanism of Action

Extracts lipophilic local anesthetic from cardiac muscle, or alternatively provides energy source for cardiac muscle, bypassing local anesthetic induced block of mitochondrial energy production Uses

• Cardiac arrest due to local anesthetic systemic toxicity • Parenteral nutrition

Onset

Rapid

Duration

Half life 0.5–1 hour Metabolism

Lipolysis to free fatty acids, utilized in metabolism Adverse Effects

Hypersensitivity reactions, fat embolus, pancreatitis, hypertriglyceridemia

CLINICAL PEARLS

• Can be administered via peripheral or central IV access • Reported use for resuscitation in life-threatening overdose with lipophilic drugs (e.g., antidepressants) • More information can be obtained at www.lipidrescue.org

HORMONES/HORMONE ANALOGS/METHERGINE Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Vasopressin (Pitressin®) and desmopressin (DDAVP®) • Vasopressin – ACLS protocol IV 40 units to replace the first or second dose of epinephrine – Shock IV infusion 0.01–0.04 units/minute – Central diabetes insipidus IV 2.5 units/hour (pediatric 0.0005 unit/kg/hour) initially, then titrate to urine output. Alternatively, IM or SQ 2–3 times daily – Variceal hemorrhage IV 0.2–0.4 units/minute IV, may titrate to 0.8 units/minute, with consideration of concurrent use of IV nitroglycerine for prevention of myocardial ischemia • Desmopressin 0.3 mcg/kg IV 30 minutes preoperatively, or 150–300 mcg intranasally 2 hours preoperatively Mechanism of Action

• Antidiuretic hormone analog • Direct vasoconstrictor at non-catecholamine binding sites (higher than physiologic doses) • Increases water reabsorption in renal tubules via intracellular increase in cAMP • Stimulates the release of von Willebrand factor from endothelial cells

Uses

Cardiac arrest/ACLS protocol, septic or vasodilatory shock, central diabetes insipidus, variceal hemorrhage, hemophilia A and von Willebrand disease Onset

1 hour if used nasally Duration

Nasal 3–8 hours, IM or SQ 2–8 hours Metabolism

• Hepatic, renal (5–15% unchanged). Consider lower doses in cirrhotics • Half-life 15 minutes with nasal administration, 10–20 minutes with parenteral administration Adverse Effects

Dysrhythmia, angina, myocardial infarction, decreased cardiac output, hypertension, bronchoconstriction, abdominal cramping, mesenteric ischemia, nausea and vomiting, diaphoresis, water intoxication, headache

CLINICAL PEARLS

• May increase Factor VIII levels • Vasoconstrictor activity maintained even in severe acidosis • Skin necrosis may occur when infused peripherally • In emergencies where no IV access is available, may administer twice the usual dose (mixed in 10–15 mL normal saline) via the endotracheal tube (per ACLS protocol). May also be given via intraosseous route • May be used in donor management after brain death at IV 0.5–4 units/hour • Monitoring of urine volume and serum electrolytes is necessary • Desmopressin is arginine vasopressin, used intranasally in some patients with von Willebrand disease or factor VIII deficiency, and may be given preoperatively to decrease bleeding

TREATMENT DRUGS

Oxytocin (Pitocin®) • Labor induction IV 0.5–1 milliunit/minute initially, may gradually increase dose by 1–2 milliunits/minute every 30–60 minutes until the desired contraction pattern is established. May reduce the dose by similar increments after 5–6 cm cervical dilation is achieved • Postpartum hemorrhage IM 10 units after delivery of placenta, or IV 10–40 units added to 1 L fluid solution, titrated to sustained uterine contraction • Pregnancy risk X, breastfeeding-compatible

Mechanism of Action

• Stimulation of G-protein mediated intracellular calcium release in uterine muscle, causing myofibril contraction • Also increases local prostaglandin production in the uterus, thereby augmenting contraction

Uses

Induction/augmentation of labor, postpartum bleeding, adjunct for medically indicated abortion of pregnancy Onset

IV 1 minute, IM 3–5 minutes Duration

IV 1 hour, IM 2–3 hours Metabolism

Rapid, via hepatic, placental, uterine and plasma oxytocinase (produced during pregnancy), some locally in mammary glands, excreted in urine as inactive metabolites Adverse Effects

Fetal bradycardia, neonatal hyperbilirubinemia, uterine hypertonus or rupture, hyponatremia, water intoxication, maternal hypo or hypertension, vasospasm, nausea and vomiting, anaphylactoid reactions, headache

CLINICAL PEARLS

• Not indicated for elective abortion (FDA Black Box Warning) • Should not be used for augmentation of labor with significant cephalopelvic disproportion or malpresentation of fetus, risk of uterine rupture, partial placenta previa, hypertonic uterus, failure to achieve adequate augmentation of labor, or if fetal distress is present and delivery is not imminent • Fetal heart monitoring is mandatory

TREATMENT DRUGS

Glucagon

• Myocardial depression IV 3–10 mg bolus (30–150 mcg/kg in children), followed by IV infusion at 3–5 mg/hour (70 mcg/kg/hour in children), titrated to hemodynamic response • Hypoglycemia IV/IM/SQ 1 mg (pediatric weight <20 kg: 0.5 mg), may be repeated after 20 minutes (along with dextrose administration) • Duodenal/gallbladder motility IV 0.25–0.5 mg • Pregnancy risk B, breastfeeding- compatible

Mechanism of Action

Increases intracellular cAMP via increase in adenylate cyclase activity, independent of betareceptors Uses

• Myocardial depression; particularly, treatment of myocardial depression or severe bradycardia due to overdose of beta or calcium channel blockers • Patient that is unresponsive to other measures (atropine, dobutamine) • Hypoglycemia • Inhibition of duodenal/gallbladder motility during ERCP

Onset

IV 5–20 minutes, IM 30 minutes, SQ 30–45 minutes (for increase in glucose levels) Duration

IV 30 minutes, SQ 60–90 minutes (glucose elevation) Metabolism

• Primarily hepatic, to inactive metabolites • Some renal/plasma inactivation

Adverse Effects

Hypertension, tachycardia, nausea, vomiting

CLINICAL PEARLS

• In treatment of myocardial depression, bolus should be administered over 3–5 minutes; may be associated with nausea and vomiting • Contraindicated in pheochromocytoma (may augment catecholamine release) • Needs adequate glycogen/glucose body stores to raise serum glucose. Useful in insulin or sulfonylurea-induced hypoglycemia. Can be given IM or SQ in patients with no IV access and hypoglycemia • 1 mg glucagon equals 1 unit of glucagon

TREATMENT DRUGS

Hydrocortisone (Solu-Cortef®)

• Widely variable. For perioperative stress prophylaxis, IV 50–100 mg (pediatric 0.5–0.75 mg/kg/day) every 6–8 hours for 24 hours. Tapering may be done by reducing the dose by 50% per day until the physiologic equivalent taken prior to surgery is reached • Pregnancy risk C, breastfeeding with caution/enters breast milk

Mechanism of Action

• Anti-inflammatory: Reverses increased capillary permeability in inflammation, decreases migration of polymorphonuclear neutrophils • Has mineralocorticoid effects

Uses

• Adrenal insufficiency, stress dosing in patients with or at risk for perioperative adrenal suppression • Septic shock

Onset

Rapid

Duration

Biologic half-life of 8–12 hours Metabolism

Hepatic, substrate/weak inducer of CYP3A4, inactive metabolites excreted in urine. Dose may need to be reduced in hepatic but not renal failure Adverse Effects

Immunosuppression, adrenal suppression, iatrogenic Cushing syndrome, hypokalemia,

hyperglycemia, weight gain/fluid retention, hyperlipidemia, hypertension, leukocytosis, myopathy, impaired wound healing, cataracts, osteoporosis

CLINICAL PEARLS

• Need to monitor electrolytes and blood glucose during administration • Has more mineralocorticoid effect than prednisone, methylprednisolone, or dexamethasone • May be associated with myopathy in severely ill/intensive care patients • Doses should be tapered after prolonged use, and depend on duration of therapy, dose, and condition treated • Physiologic equivalents for corticosteroids: Hydrocortisone 20 mg = methylprednisolone 4 mg = prednisone 5 mg = dexamethasone 0.75 mg

TREATMENT DRUGS

Methylprednisolone (Solu-Medrol®, Medrol®)

• Indication dependent. IV 10–40 mg/dose, may be repeated every 4–6 hours, pediatric 0.5– 1.7 mg/kg/day divided every 6–12 hours depending on response • Other available forms: IM, PO, depot for joint injections/epidural use • Pregnancy risk—crosses placenta, caution with breastfeeding/enters breast milk

Mechanism of Action

Regulation of gene expression, impairs neutrophil function, reverses capillary leak in inflammatory processes, modulation of metabolism Uses

Immunosuppressant for organ transplants, exacerbation of asthma, anti-inflammatory uses, acute spinal cord injury, cerebral edema, prophylaxis for IV contrast administration, septic shock Onset

Rapid via IV or IM route Duration

Dependent on product/route of administration; several hours up to weeks Metabolism

Hepatic via CYP3A4, to inactive metabolites Adverse Effects

Immunosuppression, myopathy, hyperglycemia, hypokalemia, poor wound healing, fluid retention, mental status changes, transient leukocytosis, GI perforation/hemorrhage, weight gain

CLINICAL PEARLS

• Neuromuscular blockade enhanced by corticosteroids • Many drug interactions • Doses should be tapered slowly to prevent adrenal insufficiency • May need to supplement in the perioperative period to account for surgical stress

TREATMENT DRUGS

Insulins • Type 1 diabetes SQ administration, multiple times daily, guided by frequent blood glucose determinations. Optimum dosing varies widely based on age, diet, level of control desired, disease states, formulation used, timing, and prevention of hypoglycemia. Several clinical guidelines by the American Diabetes Association, American College of Physicians have been created • Moderate-to-severe hyperkalemia IV 10 units regular insulin with 50 mL dextrose 50% (pediatric—dextrose 0.5–1 g/kg with 0.1 unit/kg regular insulin) given over 15–30 minutes. If cardiac arrest is present or imminent, may administer in <5 minutes • DKA or HHO, may bolus with IV regular insulin 0.1 unit/kg, followed by infusion at 0.1 unit/kg/hour, titrated to response/guided by blood glucose determination (various protocols exist) • Doses should be reduced by 25% in patients with CrCl 10–50, and by 50% with CrCl <10, with close monitoring • Pregnancy risk—insulin does not cross the placenta. Breastfeeding-compatible

Mechanism of Action

• Stimulation of glucose metabolism by facilitation of glucose entry into skeletal and cardiac muscle cells, and adipose tissue; facilitation of glycogen formation in liver; stimulation of protein synthesis and lipogenesis while inhibiting lipolysis • Shift potassium and magnesium from the extracellular sites to intracellular sites

Uses

• Treatment of type 1 and type 2 diabetes mellitus, gestational diabetes • Perioperative control of hyperglycemia • Prevention and treatment of diabetic ketoacidosis and hyperglycemic-hyperosmolar syndrome • Acute treatment (with glucose) of severe hyperkalemia Table 1 Insulin pharmacokinetics Metabolism

• Hepatic and renal • Plasma half-life is short in healthy patients, but prolonged in diabetics and in patients with renal insufficiency

• Varies by preparation which dictates its release characteristics after subcutaneous administration Adverse Effects

Hypoglycemia (which causes tachycardia, palpitations, diaphoresis, tremor, and irritability), clouded sensorium/confusion, seizure, hypokalemia, hypophosphatemia, hypomagnesemia

CLINICAL PEARLS

• Insulins are considered to be equipotent unit by unit and only differ in their formulation and pharmacokinetics • Allergic reactions are relatively rare since human biosynthetic insulin came into use; it is usually related to additives • Regular, NPH, and lente preparations are identical to human insulin and are mixed with additives that regulate release characteristics • Lispro, aspart, glulisine, glargine, and detemir insulins are biosynthetic human insulins with varying amino acid substitutions, allowing for unique release/pharmacokinetic profiles • Mixed preparations exist (70/30 or 50/50) of very short or short-acting insulins with intermediate-acting insulins, somewhat altering release characteristics but not total bioavailability, and used for chronic dosing • Glargine and detemir cannot be mixed with other insulins. • Regular insulin can be used IV. Other short-acting insulins (lispro, aspart, glulisine) can be administered IV also but offer no advantage over regular • Optimum perioperative glycemic control improves wound healing and infection rates, and may decrease perioperative morbidity and mortality. Optimum blood glucose levels in the perioperative period are controversial, and should be closely monitored to prevent both hyper- and hypoglycemia • Serum electrolytes, renal function, and acid-base status need to be monitored along with blood glucose in moderate to severely ill patients. Chronically, hemoglobin A1C, electrolytes, and renal function are followed

TREATMENT DRUGS

Methylergonovine (Methergine®) • IM 0.2 mg (preferred) or IV (uncommonly) after delivery of placenta or anterior shoulder, may be repeated every 2–4 hours as needed • Postpartum PO 0.2 mg 3–4 times daily for 2–7 days • Pregnancy risk C, breastfeeding caution/enters breast milk

Mechanism of Action

Produces rapid and sustained direct smooth muscle contraction primarily in the uterus, thereby reducing uterine blood loss Uses

Treatment or prevention of postpartum hemorrhage due to uterine atony or subinvolution Onset

IV almost immediate, IM 2–5 minutes, PO 5–10 minutes Duration

IM or PO 3 hours, IV 45 minutes Metabolism

Hepatic via CYP3A4 Adverse Effects

Potential for intense vasoconstriction, ischemia and gangrene, myocardial infarction, tachycardia, hyper-or hypotension, chest pain, dyspnea, diaphoresis, headache, dizziness, tinnitus, seizure, nausea and vomiting, leg cramps

CLINICAL PEARLS

• When administered intravenously, must be given slowly (over >1 minute) to prevent sudden hypertension or CVA, and should be reserved for life-threatening situations • Must be stored in the refrigerator • Methylergonovine is an ergot alkaloid, and is contraindicated in preeclampsia, eclampsia, uncontrolled hypertension, and prepartum pregnancy, and should not be given in patients on potent CYP3A4 inhibitors, such as some macrolide antibiotics, protease inhibitors, and azole antifungal agents

TREATMENT DRUGS

Carboprost tromethamine (Hemabate®) • Deep IM 250 mcg, may be repeated every 15–90 minutes, up to 8 doses (2 mg) • Pregnancy risk C, breastfeeding unknown

Mechanism of Action

Stimulates myometrial contraction and provides hemostasis at placentation site, expels contents of uterus Uses

Refractory postpartum bleeding, abortifacient Onset

Postpartum hemorrhage, blood loss reduction in about 45 minutes, as abortifacient 16 hours Duration

May need to repeat does every 15–90 minutes based on clinical response

Metabolism

Oxidized to a number of metabolites that are excreted in urine Adverse Effects

Fever, flushing, hypertension, bronchospasm, pulmonary edema, vomiting, cramping, diarrhea, leukocytosis

CLINICAL PEARLS

• IM injection sites should be rotated • Do not administer intravenously (increased risk of bronchospasm, hypertension, vomiting) • Requires refrigeration • Contraindicated in patients with acute pelvic inflammatory disease, or active cardiopulmonary, hepatic, or renal disease • Should only be used in cases of postpartum hemorrhage unresponsive to oxytocin, uterine massage, and methylergonovine

TREATMENT DRUGS

Levothyroxine (Synthroid®) • PO 100–200 mcg once daily • IV/IM doses are usually 50% of PO dose • Decrease initial doses in the elderly • Pediatric 25–150 mcg/day, varies widely by age/weight • Myxedema coma, initial IV/IM dose is 200–500 mcg • Pregnancy risk A, breastfeeding with caution/enters breast milk

Mechanism of Action

• Thyroid hormone (T4) is converted to triiodothyronine (T3) for biological activity • Binds to specific receptor in cell nucleus, regulates DNA transcription related to metabolism

Uses

Replacement for thyroid hormone after thyroidectomy, radioactive iodine therapy, hypothyroidism, TSH suppression for thyroid nodules or carcinoma Onset

PO 3–5 days. IV 6–8 hours Duration

Half-life 7 days, steady state takes 6–8 weeks Metabolism

• Excreted mostly in urine, undergoes enterohepatic recirculation

Adverse Effects

Palpitations, tremor, anxiety, weight loss, tachycardia, increased number of bowel movements, atrial fibrillation, cardiac ischemia, menstrual irregularities, osteoporosis symptoms are caused usually by overdosing

CLINICAL PEARLS

• Consider lower doses when initiating therapy in patients with cardiac disease or significant risks for cardiac disease • Doses may be titrated based on T4 and TSH levels every 4–6 weeks • Methimazole, beta-blockers, and iodide (including IV contrast agents) impair peripheral conversion of T4 to T3 • Administration of thyroid hormone may unmask/worsen symptoms of undiagnosed adrenal insufficiency

INDUCTION AGENTS, SEDATIVES, AMNESTICS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Propofol • Intravenous administration only • Induction 1–2.5 mg/kg • Maintenance of general anesthesia 100–200 mcg/kg/min, but titrated to effect • Monitored anesthesia care. Initiate infusion at 100–150 mcg/kg/min and maintain at 25–75 mcg/kg/min • Sedation for mechanically ventilated patients: 5–50 mcg/kg/min • Pregnancy Category: B • Breastfeeding-not recommended

Mechanism of Action

• Potentiates GABA neurotransmitter binding by attaching to the GABAA receptor. GABA is an

inhibitory neurotransmitter that hyperpolarizes the cell membrane (increases Clconductance) and prevents depolarization/neurotransmission • Also involves inhibition of Ach release in the hippocampus and prefrontal cortex; inhibition of NMDA in the CNS; direct depressant effect on neurons of the spinal cord; antiemetic effect by decreasing serotonin levels in the area postrema; increase of dopamine concentrations in the nucleus accumbens (a phenomenon noted with drugs of abuse and pleasure-seeking behavior) Uses

• Induction dose of choice for general anesthesia in most instances • Maintenance of anesthesia (facilitates neuromonitoring, avoidance of postoperative nausea and vomiting, non-triggering anesthetic, decreases intracranial pressure) • Sedation • Nausea and vomiting rescue • Emergence delirium • Anticonvulsant • Pruritus

Onset

Rapid due to the highly lipid soluble nature of the drug Duration

• Short awakening time secondary to redistribution from the brain to peripheral compartments

Metabolism

• Rapid hepatic metabolism • 0.3% of the drug is excreted unchanged in the urine

Adverse Effects

• CNS: Decreases cerebral metabolic activity, intracranial pressure, cerebral blood flow • Cardiac: Decreases BP (comparable to thiopental); variable effect on heart rate (typically slows following induction) • Respiratory: Dose-dependent depression

CLINICAL PEARLS

• Clearance is not affected by renal or hepatic failure • Can be administered as a prolonged continuous infusion with minimal cumulative effect • The formulation supports bacterial growth, so strict aseptic techniques should be used when drawing up and administering this medication • Can produce pain on injection (may be decreased with coadministration or prior administration of lidocaine)

TREATMENT DRUGS

Thiopental

• Intravenous administration only • Induction 3–4 mg/kg • Seizure treatment 75–125 mg • Pregnancy Category: C • Breastfeeding: Maternal medication usually compatible with breastfeeding

Mechanism of Action

• Potentiates GABA neurotransmitter binding by attaching to the GABAA receptor. GABA is an inhibitory neurotransmitter that hyperpolarizes the cell membrane (increases Clconductance) and prevents depolarization/neurotransmission

Uses

• Induction of anesthesia • Anticonvulsant • Neuroprotection

Onset

Rapid onset due to the high lipid solubility of this drug Duration

Rapid awakening after a single induction dose occurs due to redistribution of the drug from

the brain to peripheral tissues. With increasing doses or prolonged infusions, the peripheral compartments become saturated with drug and therefore may result in a longer awakening time Metabolism

Only 1% of thiopental is excreted unchanged in the urine and therefore most of the drug will undergo metabolism. 10–24% metabolized by the liver per hour Adverse Effects

• Cardiac: Slight decrease in BP; mild compensatory increase in heart rate; minimal to no cardiac depression • Respiratory: Dose-dependent depression leading to apnea • Histamine release may be seen with induction doses

CLINICAL PEARLS

• Highly protein bound, and patients with hypoalbuminemia or decreased protein states will be more sensitive to the action of thiopental • May be neuroprotective (capable of producing burst suppression/isoelectric EEG and vasoconstriction/decreased ICP) • Accidental intraarterial injection causes vasoconstriction and severe pain and can ultimately result in permanent nerve damage and gangrene

TREATMENT DRUGS

Methohexital

• Induction IV 1–1.5 mg/kg • Sedation IV 0.75–1 mg/kg • Pregnancy Category: B • Maternal medication usually compatible with breastfeeding

Mechanism of Action

Activates the inhibitory neurotransmitter GABA Uses

• Induction of anesthesia; not commonly used, except maybe for ECT • Sedation • Premedication for sedation (can be rectally administered)

Onset

Rapid onset of action Duration

Rapid awakening relies on rapid redistribution from the brain to the peripheral compartments

Metabolism

• Occurs more rapidly than thiopental

Adverse Effects

• Cardiac: Slight decrease in BP; mild compensatory increase in heart rate; minimal to no cardiac depression • Respiratory: Dose-dependent depression

CLINICAL PEARLS

• Psychomotor control returns more quickly than after thiopental • Its ability to induce seizure activity on EEG makes it an attractive choice for electroconvulsive therapy

TREATMENT DRUGS

Ketamine • Adult induction IV 1–5 mg/kg; IM 6.5–13 mg/kg • Pediatric induction IV 1–2 mg/kg; IM 5–10 mg/kg • Pregnancy Category: A • Breastfeeding: Compatible with breastfeeding

Mechanism of Action

• Antagonist of N-methyl-D-aspartate (NMDA) receptor • Binds to opioid μ receptors, muscarinic receptors, and voltage-gated calcium channels

Uses

• Induction of anesthesia • Adjunct for maintenance of anesthesia • Analgesic

Onset

Rapid, with loss of consciousness in 30–60 seconds Duration

Intermediate when compared to other induction agents. Consciousness will return in 10–20 minutes but may take 1–2 hours for complete recovery Metabolism

Metabolized by hepatic microsomal enzymes. Norketamine is a metabolite that is a metabolically active compound Adverse Effects

• CNS: Increases intracranial pressure secondary to its cerebral vasodilating property

• Cardiac: Sympathetic stimulation with induction dosing (increase in heart rate, BP, and cardiac output). It is a direct myocardial depressant, however • Respiratory: Does not produce significant respiratory depression • Other: Increased salivary and tracheobronchial secretions

CLINICAL PEARLS

• Emergence delirium makes it a less popular choice for induction. Dreams and hallucinations can occur for up to 24 hours following an induction dose. May be decreased with coadministration of benzodiazepines • Good for use in patients with severe asthma, unstable hemodynamics, and instances where spontaneous ventilation must be maintained

TREATMENT DRUGS

Dexmedetomidine

• Sedation IV loading dose 1 mcg/kg over 10 minutes, followed by 0.2–0.7 mcg/kg/hr • Pregnancy Category: C • Breastfeeding: infant risk cannot be ruled out

Mechanism of Action

Selective alpha 2 agonists. (1,600:1 ratio of alpha-2:alpha-1 agonism) Uses

• Sedation • Anxiolysis

Onset

5 minutes Duration

Elimination half life of 2 hours Metabolism

Undergoes almost complete biotransformation in the liver Adverse Effects

Rebound hypertension, rebound hyperexcitability, arrhythmias, hypotension, bradycardia

CLINICAL PEARLS

• Allows for sedation without respiratory depression; can be a good choice for weaning from mechanical ventilation • Possesses analgesic properties

• Contributes to decreasing the MAC of volatile anesthetics

TREATMENT DRUGS

Etomidate • Induction IV 0.2-0.6 mg/kg • Pregnancy Category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

• Binds to GABA receptor, and potentiates binding of GABA neurotransmitter to receptor. Results in Cl- conduction (hyperpolarizes membrane), hyperpolarization of the cell membrane, and inhibition of neurotransmission • Possesses an imidazole ring

Uses

Induction of anesthesia Onset

Rapid onset of action due to its highly lipid soluble nature Duration

Will have a shorter duration of action than thiopental but longer duration than propofol Metabolism

Undergoes hydrolysis in the liver resulting in insoluble metabolites Adverse Effects

• Minimal changes in BP, heart rate, and cardiac output with induction doses • Causes respiratory depression, but not to the same extent as propofol or thiopental

CLINICAL PEARLS

• Pain on injection • May be a suitable induction agent in a patient with unstable hemodynamics • Induction doses may cause myoclonus • Adrenocortical suppression can occur following an induction dose

TREATMENT DRUGS

Midazolam • Preoperative anxiety IV 0.02–0.08 mg/kg

• Induction of general anesthesia IV 0.1–0.3 mg/kg • Pregnancy Category: D • Breastfeeding: infant risk cannot be ruled out

Mechanism of Action

• Bind to the GABAA receptor and enhances the effects of the GABA neurotransmitter. This results in increased frequency of chloride channel opening, hyperpolarization, and inhibition of neuron firing

Uses

• Sedation • Anxiolysis • Anterograde amnesia

Onset

When compared to propofol, it has a slower onset time (1–5 minutes) Duration

Short duration of action secondary to redistribution from brain to peripheral tissue Metabolism

• Undergoes hepatic metabolism by cytochrome P450 enzyme. Metabolite formed is 1hydroxymidazolam and is pharmacologically active Adverse Effects

• CNS: Decreases cerebral metabolic activity, ICP, and cerebral blood flow • Cardiac: Induction doses decrease BP and increase HR (changes are similar to what occurs with thiopental induction) • Respiratory: Dose dependent decrease in minute ventilation

CLINICAL PEARLS

• Not able to produce an isoelectric EEG • Most commonly used drug for preoperative sedation • Hepatic clearance is five times faster than lorazepam and ten times faster than diazepam • Pain on injection is less likely than with diazepam

TREATMENT DRUGS

Lorazepam • Anxiety IV 2–6 mg/day • Sedation IV 0.02–0.06 mg/kg every 2–6 hours • Status epilepticus IV 4 mg IV over 2 minutes. • Pregnancy Category: D

• Breastfeeding: Infant risk is minimal

Mechanism of Action

• Binds to the GABAA receptor and enhances the effects of the GABA neurotransmitter. This results in increased frequency of chloride channel opening, hyperpolarization, and inhibition of neuron firing

Uses

• Sedation • Anxiolysis • Anterograde amnesia

Onset

Onset slower than Midazolam Duration

• Prolonged duration of action • Amnesia may occur for up to 6 hours after the administration of this drug

Metabolism

Undergoes conjugation in the liver to form inactive metabolites Adverse Effects

• Cardiac: Decrease in BP and increase in heart rate (comparable to thiopental) • CNS: Decreased ICP, cerebral blood flow, and cerebral metabolic activity • Respiratory: Dose dependent respiratory depression

CLINICAL PEARLS

• A more potent amnestic than midazolam or diazepam • Less pain on injection compared to diazepam • Slower onset of action and prolonged duration of action, therefore limiting its use as an anticonvulsant, preoperative sedative, or induction agent

TREATMENT DRUGS

Diazepam • Anxiety IV 2–10 mg 2–4 times/day • Sedation IV 10 mg • Seizure IV 5–10 mg every 10–15 minutes • Pregnancy Category: D • Breastfeeding: Infant risk has been demonstrated

Mechanism of Action

• Binds to the GABAA receptor and enhances the effects of the GABA neurotransmitter. This results in increased frequency of chloride channel opening, hyperpolarization, and inhibition of neuron firing

Uses

• Sedation • Anxiolysis • Anticonvulsant • Anterograde amnesia

Onset

Has intermediate onset of action similar to midazolam Duration

Prolonged duration of action compared to midazolam Metabolism

Metabolized by oxidation in the liver to desmethyldiazepam, oxazepam, and temazepam Adverse Effects

• Cardiac: Decrease in BP with mild increase in heart rate • Respiratory: Dose-dependent respiratory depression • CNS: Decreased cerebral metabolic activity, ICP, cerebral blood flow

CLINICAL PEARLS

• Can experience pain on injection with this drug • Can be used as an oral drug for preoperative sedation

TREATMENT DRUGS

Flumazenil • Benzodiazepine overdose IV 0.2 mg over 30 seconds, followed by 0.3 mg in 30 seconds if there is no return to consciousness. Maximum total dose is 3 mg Mechanism of Action

Competitive inhibitor of benzodiazepines at the GABA receptor Uses

Reversal of benzodiazepine overdose Onset

1 minute

Duration

1–4 hours

Metabolism

Liver, metabolites produced but inactive Adverse Effects

• Cardiac dysrhythmias, chest pain, hypotension, hypertension, diaphoresis, nausea and vomiting, confusion, dizziness, shivering, somnolence, seizure, anxiety, slurred speech, withdrawal symptoms

CLINICAL PEARLS

Following a return of consciousness and improved mental function, patients must be monitored neurologically; the duration of action of the inciting benzodiazepine can be significantly longer than flumazenil

IV ANTIHYPERTENSIVES Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Nitroprusside (Nipride®) • IV infusion 0.5-10 mcg/kg/min • Doses should be limited in renal or hepatic failure due to an increased risk of toxicity • IV pediatric maximum dose of 5 mcg/kg/min • Pregnancy risk C, breastfeeding unknown

Mechanism of Action

• Vascular smooth muscle relaxation via production of nitric oxide in endothelial cells and impaired intracellular calcium release • Produces vasodilation in arterial > venous/capacitance vessels; primarily provides afterload reduction Uses

Hypertensive emergency, controlled hypotension, aortic aneurysm dissection, afterload reduction, peripheral vasospasm Onset

1–2 minutes Duration

• 1–10 minutes • Thiocyanate half-life 2–7 days

Metabolism

• In addition to nitric oxide, cyanide ions are also released. They bind to thiosulfate to form thiocyanate via rhodanese enzyme in the liver and kidney • Thiocyanate is excreted renally • Some cyanide is bound by methemoglobin

Adverse Effects

• Reflex tachycardia, hypotension, headache, increased intracranial pressure, disorientation, restlessness, impairment of cerebral autoregulation and hypoxic pulmonary vasoconstriction, angina/ischemia, cyanide or thiocyanate toxicity (miosis, tinnitus, hyperreflexia, restlessness, weakness) • Rebound hypertension may occur upon discontinuance

CLINICAL PEARLS

• Preparation: Mix in D5W, protect from light • Consider coadministering with a beta blocker (for induced reflex tachycardia) • Tachyphylaxis can occur with prolonged use and is associated with malnutrition or impending cyanide toxicity • Serum thiocyanate levels should be monitored in patients receiving high doses of nitroprusside for >24 hours (may not aid with detecting toxicity; may be confirmatory in patients with symptoms) • Extreme caution should be exercised when administering to patients intracranial hypertension

TREATMENT DRUGS

Nitroglycerin • IV 0.5-10 mcg/kg/min • Sublingual tablet 0.15–0.6 mg or sublingual spray 0.4 mg/spray every 5 minutes up to 3 doses within 15 minutes • Ointment 0.5–2 inches (0.15 mcg/inch) measured on supplied paper every 4–8 hours. • Transdermal patch 0.2–0.4 mg/hr/day initially, up to 0.4–0.8 mg/hr/day • Controlled release tablet 5–10 mg every 24 hours • Nitrate free intervals of 10–12 hrs/day are recommended in patients using NTG products chronically • Pregnancy Category: C, breastfeeding-unknown

Mechanism of Action

• Vascular smooth muscle relaxation via production of nitric oxide in endothelial cells and impaired intracellular calcium release • Venodilation > arterial dilation; primarily provides preload reduction

Uses

Angina pectoris/acute coronary syndrome, vasospasm, CHF, hypertension, uterine relaxation, intraoperative hypotension, esophageal spasm Onset

IV-almost immediate. SL tab or spray-1–3 minutes. Topical/transdermal-15–30 minutes. Controlled release tablet-1 hour Duration

IV-3–5 minutes, SL tab/spray-25 minutes. Topical ointment-7 hours. Transdermal patch-10– 12 hours. Controlled release tablet-4–8 hours Metabolism

Hepatic; blood via a reductase enzyme; inactive metabolites are excreted in urine.

Adverse Effects

Headache, dizziness, flushing, reflex tachycardia, hypotension, increased intracranial pressure, impairment of cerebral autoregulation and hypoxic pulmonary vasoconstriction, nausea, tolerance (develops within 24–48 hours), withdrawal effects (headache, angina), methemoglobinemia

CLINICAL PEARLS

• Concurrent beta blockade may be required for reflex tachycardia • Tolerance to hemodynamic and antianginal effects may occur especially with prolonged use or high doses • Severe hypotension may occur in patients with hypovolemia, or taking erectile dysfunction drugs • Nitrate free intervals of 10–12 hrs/day restore responsiveness

TREATMENT DRUGS

Hydralazine (Apresoline®) • IV 5–20 mg every 15–20 minutes, may be infused 0.5–10 mg/hr • May need to increase dosage interval in patients with renal failure • Pediatric IV 0.1–0.2 mg/kg/dose (not to exceed 20 mg) every 4–6 hours • Pregnancy risk C, enters breast milk, breastfeeding with caution

Mechanism of Action

• Decreases intracellular calcium release, thereby causing direct arterial vasodilation via smooth muscle relaxation • Little effect on venous/capacitance beds

Uses

Hypertension, pregnancy induced hypertension/preeclampsia, afterload reduction, CHF Onset

IV-10–15 minutes, oral-20–30 minutes Duration

IV-1–4 hours, oral-up to 8 hours. Half-life prolonged in renal failure Metabolism

Hepatic acetylation to inactive metabolites; excreted in urine; small amount unchanged Adverse Effects

Reflex tachycardia, hypotension, angina, tolerance, fluid retention, headache, increased intracranial pressure, impaired cerebral autoregulation, nausea/vomiting, diarrhea,

peripheral neuritis, lupus-like syndrome

CLINICAL PEARLS

• May require concurrent beta blockade for induced reflex tachycardia. May require diuretic if fluid retention/tolerance is induced • Metabolism and duration of action is variable due to pharmacogenomic variation (fast versus slow acetylators may be responsible for increased toxicity or duration of action) • Decreased mortality in black patients with CHF when combined with nitrate as a component of multimodal therapy

TREATMENT DRUGS

Fenoldopam (Corlopam®) • IV infusion 0.03–0.1 mcg/kg/min • Pediatric 0.2 mcg/kg/min, may be increased 0.05–0.1 mcg/kg/min every 15 minutes until BP target achieved, up to 1.6 mcg/kg/min • Labeling limits use to 48 hours duration • Pregnancy risk B, breastfeeding-unknown

Mechanism of Action

• Selective dopamine-1 receptor agonist that vasodilates renal arterioles and maintains/increases renal blood flow; results in natriuresis/diuresis Uses

Hypertensive crisis, postoperative hypertension, renal protection in cardiac surgery Onset

5–15 minutes Duration 1 hour

Metabolism

Hepatic, mostly inactive metabolites (one weakly active), excreted in urine Adverse Effects

Reflex tachycardia, atrial dysrhythmias, angina, hypotension, hypokalemia, headache, increased intracranial pressure, edema, nausea, diarrhea, abdominal pain Table 1 Orally administered alpha antagonists

CLINICAL PEARLS

• Effects are predictable, rapidly reversible, and have the advantage of maintaining renal

blood flow/diuresis • No requirement for dose adjustment in renal, hepatic, or cardiac failure • May not require arterial line for monitoring • Use with caution in patients with glaucoma/increased intraocular pressure • May increase portal pressure in patients with cirrhosis • Relatively expensive compared to alternatives

TREATMENT DRUGS

Phentolamine (Regitine®, Oraverse®) • IV 5–20 mg for hypertensive crisis • Pediatric 0.05–0.1 mg/kg/dose • Pregnancy risk C, breastfeeding-unknown

Mechanism of Action

• Vasodilation occurs via direct, competitive alpha-1 and alpha-2 blockade, as well as some direct vascular smooth muscle relaxation • Enhances neural norepinephrine release, increasing cardiac output and heart rate • Reduces alpha-1 mediated urethral stricture at bladder neck that cause symptoms of BPH

Uses

• Hypertensive crisis, pheochromocytoma, treatment of IV drug extravasation/dermal necrosis induced by agents with alpha agonist/vasoconstrictive activity • Oraverse is used to reverse local anesthesia induced soft tissue/lip anesthesia in dental anesthesia when local anesthetic is given with a vasoconstrictor

Onset

IV-within 2 minutes Duration

IV-10–15 minutes Metabolism

Hepatic, 10% is excreted unchanged into urine Adverse Effects

Reflex tachycardia, angina, hypotension, postural hypotension, syncope, fluid retention, hyperperistalsis, abdominal pain, diarrhea. Floppy iris syndrome with oral alpha antagonists

CLINICAL PEARLS

• Extravasation: Administer 5–10 mg (diluted in 10 cc of normal saline) into the affected dermal tissue within 12 hours of event (use a small needle; improvement usually seen within 1 hour)

• In pheochromocytoma, use should precede beta blockade. Phenoxybenzamine is an alternative oral agent for alpha blockade in patients with pheochromocytoma. It produces irreversible alpha blockade (until new receptors are generated), with a long half-life, and tends to accumulate over time

TREATMENT DRUGS

Clonidine (Catapres®) • PO 0.1–0.8 mg/day in 2 divided doses • Acute HTN may give 0.1 mg every hour up to 0.7 mg until BP controlled • Transdermal patch 0.1 mg/24 hrs. Every 7 days, can increase by 0.1 mg increments weekly up to 0.6 mg/day • Epidural 30 mcg/hr • Doses should begin at a lower range in elderly patients or those with renal failure • Pregnancy risk C, breastfeeding not recommended

Mechanism of Action

• Selective, centrally acting alpha-2 agonist that decreases sympathetic outflow from brainstem • Analgesic action occurs via sites in the spinal cord that decrease pain signal transmission

Uses

HTN, adjunct in neuraxial/regional blocks, preanesthetic sedative, treatment of shivering, opioid/alcohol withdrawal, ADHD Onset

30–60 minutes, patch 48–72 hours (initial application) Duration

PO-6–10 hours Metabolism

Hepatic metabolism to inactive metabolites that are excreted in the urine (40–60% unchanged) Adverse Effects

Bradycardia, hypotension, orthostasis, sedation, weakness, xerostomia, rash, impotence. Local skin irritation with patch

CLINICAL PEARLS

• Decreases MAC • The risk of intraoperative hypotension needs to be balanced against that of rebound hypertension with abrupt discontinuation in the perioperative period. Concurrent beta

blockade may enhance rebound hypertension due to unopposed alpha induced vasoconstriction • Minimal respiratory depression/no potentiation of opiate-induced respiratory depression • Tolerance to BP lowering effects may develop with long-term therapy • Not recommended for epidural use in obstetrics

TREATMENT DRUGS

Methyldopa (Aldomet®) • PO 250–1000 mg (pediatric 10–65 mg/kg/day) twice daily, up to 3 g maximum/day • IV 250 mg (pediatric 5–10 mg/kg/dose) every 6–8 hours infused over 30 minutes, maximum 1 g every 6 hours • Doses require adjustment in patients with renal dysfunction • Pregnancy risk B, caution with breastfeeding

Mechanism of Action

Acts as a false neurotransmitter in CNS that decreases sympathetic outflow Uses

• Treatment of moderate-to-severe pregnancy induced hypertension • Hypertension

Onset

Peak effect-3–6 hours; PO/IV duration 12–24 hours Duration

12–24 hours Metabolism

Hepatic and intestinal, metabolites excreted in urine Adverse Effects

Fluid retention, edema, bradycardia, orthostasis, sedation, depression, xerostomia, liver dysfunction, hemolytic anemia

CLINICAL PEARLS

• Commonly used in the OB setting for moderate-to-severe PIH. Maintains uterine blood flow. More effective when used with a diuretic • Anesthetics may augment hypotensive effects • Contraindicated in patients with severe hepatic disease or those taking MAO inhibitors

MUSCLE RELAXANTS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Succinylcholine • Intubation dose IV 0.6–1.1 mg/kg • Rapid-sequence induction intubating dose IV 1.5 mg/kg in adults • Pediatrics (infants and small children) IV 2 mg/kg or IM 3–4 mg/kg • Pregnancy Category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

• Depolarizing neuromuscular blocker: Binds to the nicotinic cholinergic receptor and causes depolarization (just like acetylcholine) • However, the hydrolysis of succinylcholine is much slower than that of acetylcholine, and the succinylcholine molecule then occupies this site preventing further depolarization Uses

• Muscle relaxation for intubation or surgical procedures • Rapid-sequence inductions

Onset

Rapid onset time, 30–60 seconds to achieve intubating conditions Duration

Short duration 3–5 minutes Metabolism

Hydrolysis by pseudocholinesterase enzymes Adverse Effects

Increases intracranial pressure, serum potassium, intraocular pressure, intragastric pressure; triggers malignant hyperthermia; can cause sinus bradycardia or junctional rhythms with repeat dose; postoperative myalgias, myoglobinuria, incomplete jaw relaxation and masseter jaw rigidity

CLINICAL PEARLS

• Despite its many side effects, succinylcholine remains in use because of its ability to achieve rapid intubating conditions without the prolonged action of paralysis • Must be avoided in patients with muscular dystrophy, denervation injuries, extensive burns,

prolonged immobility, and spinal cord transection as it can cause malignant hyperkalemia

TREATMENT DRUGS

Pancuronium • Intubation dose (adult/pediatric) IV 0.04–0.1 mg/kg • Pregnancy Category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Competitively binds to the postsynaptic nicotinic cholinergic receptor at the neuromuscular junction Uses

Muscle relaxation for intubation or surgical procedures Onset

Longer onset time approximately 2–4 minutes secondary to its increased potency Duration

Long duration of action 60–120 minutes Metabolism

Undergoes renal and hepatic metabolism Adverse Effects

Vagolysis and sympathetic activation, resulting in an increase in heart rate, blood pressure, and cardiac output

CLINICAL PEARLS

• Neuromuscular blockade is more difficult to reverse than intermediate non-depolarizers • Generic formulation renders this drug a cheap viable option to the newer intermediateacting non-depolarizing neuromuscular blockers

TREATMENT DRUGS

Vecuronium • Intubation (adult/pediatric) IV 0.1 mg/kg • Pregnancy Category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Competitively binds to the postsynaptic nicotinic cholinergic receptor at the neuromuscular junction Uses

Muscle relaxation for intubation and surgical procedures Onset

Intermediate onset time at 3–4 minutes Duration

Intermediate duration 30–45 minutes, but dose-dependent Metabolism

Hepatic metabolism and renal excretion. Vecuronium undergoes a spontaneous deacetylation as it enters into hepatocytes Adverse Effects

Typically does not cause changes in hemodynamics

CLINICAL PEARLS

• Prolonged duration of action is seen in patients with renal and hepatic disease at higher doses • May precipitate when administered with thiopental

TREATMENT DRUGS

Rocuronium • Intubation dose (adult/pediatric) IV 0.6 mg/kg • Rapid-sequence induction intubation dose (adult/pediatric) IV 0.6–1.2 mg/kg • Pregnancy Category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Competitively binds to the postsynaptic nicotinic cholinergic receptor at the neuromuscular junction Uses

Muscle relaxation for intubation and surgical procedures Onset

Short onset at 1–2.5 minutes

Duration

Intermediate duration 30–40 minutes Metabolism

Most of the drug is excreted unchanged in the urine, feces, or bile Adverse Effects

No hemodynamic changes occur. Histamine is not released, and anaphylactic reactions do not typically occur

CLINICAL PEARLS

• The onset of rocuronium is similar to succinylcholine at 3–4 times the ED95, but duration of action at this dose mimics that of long-acting neuromuscular blockers

TREATMENT DRUGS

Pipecuronium • Intubation dose 0.1 mg/kg • Pregnancy Category: C

Mechanism of Action

Competitively binds to the postsynaptic nicotinic cholinergic receptor at the neuromuscular junction Uses

Muscle relaxation for intubation and surgical procedures Onset

Slow onset time at 3–5 minutes Duration

Long duration drug lasting 90–130 minutes Metabolism

Large amount of renal clearance Adverse Effects

Does not have the same cardiovascular changes that occur with pancuronium. No histamine is released, rare anaphylactic reactions occur

CLINICAL PEARLS

• Developed as a drug similar in duration and nature to pancuronium without the

cardiovascular effects. It has not gained popularity secondary to the introduction of the short-onset and intermediate-duration neuromuscular blockers • Prolonged duration of action with renal failure; unaffected by liver disease

TREATMENT DRUGS

Atracurium • Intubating dose IV 0.4–0.5 mg/kg • Pregnancy Category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Competitively binds to the postsynaptic nicotinic cholinergic receptor at the neuromuscular junction Uses

Muscle relaxation for intubation and surgical procedures Onset

Intermediate onset time 3–4 minutes Duration

Intermediate duration lasting 35–45 minutes Metabolism

• Undergoes spontaneous degradation at physiologic pH and temperature • Nonspecific plasma esterases contribute to the metabolism

Adverse Effects

Releases histamine potentially, resulting in hypotension, tachycardia, skin flushing, and bronchospasm

CLINICAL PEARLS

One of the metabolites of atracurium is laudanosine. This chemical was implicated in causing seizures in animals, but this was never demonstrated to occur in humans at normal doses

TREATMENT DRUGS

Cisatracurium • Intubating dose IV 0.15–0.2 mg/kg • Pregnancy Category: B

• Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Competitively binds to the postsynaptic nicotinic cholinergic receptor at the neuromuscular junction Uses

Muscle relaxation for intubation and surgical procedures Onset

Slow onset time taking 5–7 minutes Duration

Intermediate duration of action lasting 35–45 minutes Metabolism

Spontaneous degradation by Hofman elimination, with a minimal amount of renal clearance Adverse Effects

• No histamine release occurs with this drug • Laudanosine metabolite is produced with cisatracurium, but in much smaller doses than with atracurium

CLINICAL PEARLS

• Cisatracurium is more potent than atracurium and has a slower onset of action • Devoid of histamine-release seen with atracurium • Because of its spontaneous metabolism, cisatracurium is a good drug choice for patients with liver and kidney disease

TREATMENT DRUGS

Doxacurium • Intubating dose IV 0.07 mg/kg • Pregnancy Category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Competitively binds to the postsynaptic nicotinic cholinergic receptor at the neuromuscular junction Uses

Muscle relaxation for intubation and surgical procedures Onset

Slow onset time 5–10 minutes Duration

Long duration of action 40–120 minutes Metabolism

Renal and hepatic metabolism Adverse Effects

• No histamine release occurs • Prolonged duration of action

CLINICAL PEARLS

• Prolonged duration of action with prolonged onset time makes this drug difficult to use with shorter and intermediate-duration procedures • The duration of action is prolonged in both renal and hepatic failure patients

NSAIDS

Alan J. Kover, MD, PharmD

TREATMENT DRUGS

NSAIDs-non specific

Mechanism of Action

• Reversible (aspirin is irreversible), non specific cyclooxygenase inhibition of both COX-1 (constitutive, as in gastric mucosa, platelets, and kidneys) and COX-2 (inducible at sites of injury/inflammation) • Results in decreased levels of prostaglandins that mediate normal processes (protective layer of mucus in stomach, platelet aggregation, maintenance of renal perfusion), and proinflammatory responses (fever, pain, inflammation) Table 1 Non specific non steroidal antiinflammatory agents Uses

• Analgesic; also functions as an adjunctive agent in multimodal pain therapy • Antipyretic • Antiinflammatory • Arthritic conditions • Dysmenorrhea • Aspirin is used for anticoagulation as an antiplatelet agent

Adverse Effects

• Gastric ulceration and bleeding, dyspepsia, nausea, decreased renal perfusion, fluid retention/edema, hypertension, bleeding, hepatocellular injury, exacerbation of asthma, urticaria, allergic reactions, tinnitus • Aspirin prolongs bleeding time

CLINICAL PEARLS

• Synergistic effects with opiates, allowing for decreased doses of opiates and without additive respiratory depression • Ceiling effect exists for NSAIDs (increasing dose may not increase efficacy) • Disproportionate use and complication rate among the elderly • COX-2 expression has a role in oncogenesis • NSAIDs have been associated with an increased risk of thrombotic events (both myocardial infarction and stroke), especially after CABG surgery • Renal insufficiency or severe hepatic disease may require dose reduction or preclude use • NSAIDs should be administered with food

• Ibuprofen can be given up to 24 hours preoperatively, other NSAIDs should be discontinued 3 days preoperatively (full dose aspirin 7 days if not contraindicated), to reduce the possibility of bleeding complications • Association with asthma, rhinitis/nasal polyps, and aspirin allergy

TREATMENT DRUGS

Celecoxib (Celebrex) • PO 200 mg once daily or 100 mg twice daily, may increase to 400 mg twice daily • Children >age 2–10 years up to 25 kg: PO 50 mg BID • Children >25 kg: PO 100 mg BID • Pregnancy Category: C <30 weeks gestation; D >30 weeks gestation • Breastfeeding with caution/enters breast milk

Mechanism of Action

• Selective COX-2 inhibition (inflammation inducible) • Does not inhibit COX-1, except at high doses

Uses

• Analgesia • Antiinflammatory • Arthritis • Dysmenorrheal • Should not be used for pain control after CABG

Onset

Time to peak 3 hours Duration

Half-life 11 hours Metabolism

Hepatic, via CYP2C9, to inactive metabolites; majority excreted in feces, <30% urine Adverse Effects

• Same as non specific NSAIDs • Hypersensitivity reactions in patients with sulfa allergy

CLINICAL PEARLS

• Decreased GI side effects and platelet effects compared to non specific COX inhibitors • Analgesia comparable to other NSAIDs • Possibility of increased risk of MI or CVA compared to non specific COX inhibitors

TREATMENT DRUGS

Acetaminophen (Tylenol®, Ofirmev®-new IV formulation) • Oral or rectal 325–650 mg every 4–6 hours, or 1000 mg every 6–8 hours, not to exceed 4 g/day • Age <12: PO or PR 10 to 15 mg/kg every 4–6 hours, not to exceed 2.6 mg/day • IV 650 mg every 4 hours, or 1000 mg every 6 hours, in patients weighing 50 kg or more. In patients weighing <50 kg, 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, not to exceed 75 mg/kg/day • Doses require adjustment in severe renal insufficiency, and should not exceed 2 g/day in alcoholic or malnourished patients • Pregnancy Category: C for IV formulation; recommended oral doses have not been shown to increase the risk of teratogenesis • Breastfeeding: Enters breast milk and should be used with caution

Mechanism of Action

• Believed to inhibit CNS prostaglandin production involved in pain pathways via non specific COX inhibition (CNS > peripheral) • Inhibition of the hypothalamic heat regulation center responsible for antipyretic action

Uses

• Analgesic for mild-moderate pain • Antipyretic • Dysmenorrhea • Weak antiinflammatory activity

Onset

30 minutes, peak 2–3 hours Duration 4 hours

Metabolism

Hepatic, to inactive metabolites. <5% to a toxic metabolite via CYP2E1. The toxic metabolite is conjugated to an innocuous compound until glutathione stores are exhausted (as in overdose) Adverse Effects

• Nausea and vomiting (especially with IV form), hyper/hypotension, edema, tachycardia, nephrotoxicity, rash, urticaria, anaphylaxis, blood dyscrasias, liver enzyme elevation, acute hepatic failure with high doses/overdose • Liver damage more common in alcoholics or those with preexisting liver disease

CLINICAL PEARLS

• Alternative to NSAIDs when GI, platelet, or renal adverse effects are to be avoided • Acetylcysteine (Mucomyst®) is an antidote for acetaminophen overdose; must be given per time dependent/serum level based nomogram to prevent liver failure for acute ingestion. It is not used in cases of toxicity due to chronic ingestion • Commonly combined with antihistamines and decongestants in OTC preparations for colds, allergies, influenza etc • Many acetaminophen-opiate combinations exist, (Percocet®, Vicodin®, Tylenol #3® etc.) • Total daily dose should not exceed 4 g/day, including doses received in combination products • Caution with medications that are cytochrome inducers (may increase toxicity)

OPIOIDS AND ANALGESICS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Codeine • PO 15–60 mg every 4–6 hours • Pregnancy category: C • Breastfeeding: Infant risk is minimal

Mechanism of Action

Agonist at the opioid receptor Uses

Mild-to-moderate pain, cough suppression Onset

Analgesic effect 30–60 minutes Duration

4–8 hours

Metabolism

Converted by the liver (via CYP2D6) to morphine Adverse Effects

Euphoria, nausea and vomiting, sedation, constipation, mild bradycardia, hypotension, respiratory depression, lightheadedness, dizziness, orthostatic hypotension

CLINICAL PEARLS

• Avoid alcohol consumption, as it can increase the CNS depressant effect of codeine • Genetic defects in the CYP2D6 enzyme can result in ineffective analgesia

TREATMENT DRUGS

Morphine • IV 1–5 mg over at least 1 minute, titrated every 5 minutes for moderate-to-severe pain • IV infusion 0.5–4 mg/hr with no maximum dose • Pregnancy category: C

• Breastfeeding: Infant risk is minimal

Mechanism of Action Opioid agonists Uses

Analgesia Onset

• IV 1 minute with peak effect 5–20 minutes • Epidural or spinal onset 15–60 minutes

Duration

• IV 2–7 hours • Epidural or spinal 6–24 hours

Metabolism

Hepatic, glucuronidation rather than cytochrome P450 system Adverse Effects

Respiratory depression, pruritus, sedation, nausea, vomiting, constipation, urinary retention, hypotension, bradycardia, arrhythmias, chest wall rigidity, blurred vision, euphoria, dysphoria, biliary tract spasm, miosis

CLINICAL PEARLS

• Morphine can cause histamine release (with resultant bronchospasm and pruritus) • Reversal of morphine with naloxone is effective for reducing essentially all side effects except nausea and vomiting and urinary retention

TREATMENT DRUGS

Hydromorphone • IV 0.2–1 mg q12–15 minutes; titrate based on patient’s pain level and respiratory/neurologic status • Pregnancy category: C • Breastfeeding: Infant risk is minimal

Mechanism of Action

Synthetic opioid agonists Uses

• Analgesia • Anesthesia

• Pre-medication • Antitussive

Onset

IV 15 minutes, PO 15–30 minutes, epidural 5 minutes Duration

IV 2–4 hours, PO 4–6 hours, epidural 10–16 hours Metabolism Hepatic

Adverse Effects

Hypotension, bradycardia, arrhythmias, bronchospasm, laryngospasm, nausea and vomiting, constipation, respiratory depression, CNS depression, itching, urinary retention, miosis, chest wall rigidity

CLINICAL PEARLS

• Five to ten times more potent than morphine • It is very effective for moderate-to-severe pain • Consider dose reduction in the elderly, particularly when other CNS depressants are used

TREATMENT DRUGS

Oxycodone • PO 5–15 mg every 4–6 hours for opioid naive patients • Pregnancy category: B • Breastfeeding: Infant risk has been demonstrated

Mechanism of Action Opioid agonist Uses

Treatment of chronic or acute pain, moderate to severe Onset

1 hour

Duration

3–4 hours

Metabolism

Metabolized extensively by the CYP 450 system in the liver to an active metabolite. The

active metabolite does not have a stronger affinity for the mu receptor than its parent compound Adverse Effects

Cardiac arrest, heart failure, hypotension, respiratory depression, constipation, nausea and vomiting, pruritus, sedation, seizures, high abuse dependence potential, miosis

CLINICAL PEARLS

• Controlled release tablets must be swallowed whole and not altered in any way, otherwise it may result in overdose • After using for a few weeks, it should be tapered to discontinuation. Abrupt discontinuation of the medication can lead to opioid withdrawal symptoms

TREATMENT DRUGS

Hydrocodone • PO 10 mg • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Opioid agonist and typically used in combination with an NSAID Uses

• Acute pain

Onset

1 hour

Duration

4–6 hours

Metabolism

Extensive conversion in the liver by the CYP2D6 enzyme to hydromorphone (more active analgesic) Adverse Effects

Myocardial infarction, CHF, respiratory failure, bronchospasm, acute renal failure, sedation, cerebrovascular accident, GI hemorrhage, GI ulcer, nausea and vomiting, constipation, liver failure, jaundice, pruritus

CLINICAL PEARLS

• Major component of Vicodin®, Norco®, and Lortab®

TREATMENT DRUGS

Meperidine • Postoperative shivering IV 5–10 mg • Analgesia IV 10 mg and titrate at a minimum of 5 minutes according to patient response • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Synthetic opioid agonist Uses

Analgesia, postoperative shivering Onset

IV <1 minute, PO 30–45 minutes Duration

IV and PO 2–4 hours Metabolism

Hepatic, active metabolite produced—normeperidine Adverse Effects

Hypotension, respiratory depression, seizures, sedation, dysphoria, constipation, chest wall rigidity, pruritus, delirium with repeated doses

CLINICAL PEARLS

• Has approximately 1/100th the potency of morphine with a shorter duration of action • Can cause severe and fatal reactions (hyperthermia, hypertension, seizures) if given to patients on MAO inhibitors, and therefore use should be avoided in these patients • Naloxone reverses the effects of meperidine, but may precipitate seizures if used in patients on chronic therapy

TREATMENT DRUGS

Fentanyl • Analgesia bolus range IV 2–50 mcg/kg • Pregnancy category: C

• Breastfeeding: Infant risk is minimal

Mechanism of Action

Synthetic opioid agonist Uses

Analgesic, sedation Onset

IV 30 seconds, spinal 10 minutes, transdermal 12–24 hours, oral transmucosal 5–15 minutes Duration

IV 30–60 minutes, spinal 1–2 hours, transdermal 3 days, oral transmucosal 1–2 hours Metabolism

Hepatic CYP 450 system Adverse Effects

Hypotension, bradycardia, respiratory depression, sedation, constipation, pruritus, dizziness, blurred vision, seizures, nausea and vomiting, mitosis, chest wall rigidity, abuse dependency potential, urinary retention

CLINICAL PEARLS

• Fentanyl is 75–125 times more potent than morphine • Its high lipid solubility results in a rapid onset of action and shorter duration of action than morphine. Fentanyl’s rapid onset makes it suitable during induction to blunt the pain response to laryngoscopy and intubation • Naloxone reverses the effects of fentanyl

TREATMENT DRUGS

Sufentanil • Analgesia IV 1–8 mcg/kg • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Synthetic opioid agonist Uses

Analgesia, sedation Onset

IV 1–3 minutes, Spinal 4–10 minutes Duration

IV 20–45 minutes, Spinal 2–4 hours Metabolism

Hepatic metabolism Adverse Effects

Respiratory depression, hypotension, nausea and vomiting, constipation, sedation, pruritus, dysphoria, euphoria, miosis, chest wall rigidity, dose dependent bradycardia, urinary retention

CLINICAL PEARLS

• Sufentanil has 5–7 times greater potency than fentanyl • Its rapid onset makes it a good choice prior to induction to blunt the sympathetic response to laryngoscopy and intubation; also decreases the amount of induction agent needed • Naloxone reverses its effects

TREATMENT DRUGS

Alfentanil • Induction of anesthesia IV 20–50 mcg/kg plus maintenance of 5–15 mcg/kg every 15 minutes • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Synthetic opioid agonists Uses

Analgesia Onset

IV 1–2 minutes Duration

IV 10–15 minutes Metabolism

Hepatic elimination Adverse Effects

Bradycardia, hypotension, arrhythmias, respiratory depression, sedation, pruritus, nausea and vomiting, constipation, urinary retention, miosis, euphoria, dysphoria, abuse dependency potential, chest wall rigidity

CLINICAL PEARLS

• Capable of producing a deep level of analgesia and is also associated with more hypotension and bradycardia than fentanyl or sufentanil • Repeated doses or continuous infusions do not cause significant accumulation in the body; therefore rapid reversal effects will occur when an infusion is discontinued

TREATMENT DRUGS

Remifentanil • Induction IV 1 mcg/kg followed by an infusion of 0.1–2 mcg/kg/min • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Synthetic opioid agonist Uses

Analgesia, sedation Onset

Rapid onset of action Duration

3–10 minutes Metabolism

Plasma esterases Adverse Effects

Apnea, respiratory depression, sedation, pruritus, nausea and vomiting, constipation, urinary retention, hypotension, bradycardia, ventricular arrhythmias, chest wall rigidity, abuse dependency potential, seizures, bronchospasm

CLINICAL PEARLS

• Excellent choice to maintain deep levels of analgesia and still allow for a rapid awakening (e.g., carotid endarterectomies or craniotomies where a rapid neurological assessment needs to be performed) • Does not accumulate even after very high doses or prolonged infusions

TREATMENT DRUGS

Nalbuphine • Moderate–to-severe pain IV 10 mg every 4–6 hours. Total daily dose not to exceed 160 mg/day • Pregnancy category: B • Breastfeeding: Infant risk is minimal

Mechanism of Action

Opioid agonist–antagonist Uses

Moderate-to-severe analgesia, pruritus caused by opioid administration Onset

IV 2–3 minutes Duration 5 hours

Metabolism

Liver, cytochrome P450 Adverse Effects

Respiratory depression, bradycardia, hypotension, abuse dependency potential, sedation, nausea and vomiting, pruritus, dysphoria

CLINICAL PEARLS

• Caution should be used when administering nalbuphine to patients that are on chronic opioid therapy; may precipitate withdrawal symptoms • Has equal analgesic potency with morphine but 1/4th the antagonist potency as naloxone • Exhibits a ceiling effect on respiratory depression and analgesia; thus allows for reversal of opioid side effects while maintaining analgesia

TREATMENT DRUGS

Buprenorphine • Analgesia IV 0.3–0.6 mg every 6 hours • Pregnancy category: C • Breastfeeding: Infant risk has been demonstrated

Mechanism of Action

Semisynthetic opioid agonist and antagonist Uses

Moderate-to-severe analgesia, induction of detoxification for patients on illicit drugs Onset

Rapid onset due to its highly lipophilic nature (5–15 minutes IV) Duration

6–8 hours

Metabolism Hepatic

Adverse Effects

Respiratory depression, bronchospasm, hypotension, bradycardia, seizures, hepatotoxicity, sedation, nausea and vomiting, miosis

CLINICAL PEARLS

• Has a ceiling effect on respiratory depression but no such effect on analgesia • Most of buprenorphine’s properties can be described by its high affinity to the mu receptor and its slow dissociation from opioid receptors

TREATMENT DRUGS

Naloxone • Opiate reversal IV 0.04–0.4 mg, may need to be repeated to attain desired response • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

Pure Opioid antagonist Uses

Reversal of adverse side effects of opioid overdose Onset

1–2 minutes Duration

60 minutes

Metabolism

Hepatic, cytochrome P450

Adverse Effects

Cardiac arrest, ventricular fibrillation, seizures, tachycardia, hypertension, nausea and vomiting, pulmonary edema, diaphoresis, withdrawal symptoms

CLINICAL PEARLS

• Does not possess any opioid agonist properties; therefore does not cause respiratory depression or sedative effects • Should be titrated to effect rather than bolusing with a large dose. Large doses can precipitate cardiac arrhythmias and pulmonary edema

TREATMENT DRUGS

Naltrexone • Opioid addiction PO 50 mg/day • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action Opioid antagonist Uses

Treatment of opioid addiction, treatment of alcohol dependence Onset

1 hour

Duration 4 hours

Metabolism

Hepatic metabolism, cytochrome P450 system, active metabolite is formed (6-beta-naltrexol) Adverse Effects

Withdrawal symptoms, depression, suicidal ideations, hepatotoxicity, insomnia, nausea and vomiting, dizziness, fatigue, constipation

CLINICAL PEARLS

• Can precipitate liver dysfunction; thus needs to be monitored

TREATMENT DRUGS

Tramadol

• Analgesia PO 50–100 mg every 4–6 hours to a maximum of 400 mg/day • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

• Central opioid agonist • Weak serotonin/norepinephrine reuptake inhibitor

Uses

Moderate-to-severe analgesia Onset

30 minutes Duration

3–7 hours

Metabolism

Hepatic, cytochrome P450 system, Cytochrome 2D6 produces an active metabolite Adverse Effects

Drowsiness, sweating, nausea and vomiting, mild sedation, mild respiratory depression, serotonin syndrome, hallucinations, tachycardia, hyperthermia, hyperreflexia, muscular incoordination, coma, angioedema, bronchospasm, orthostatic hypotension, suicidal ideations, abuse dependency potential

CLINICAL PEARLS

• There has been an increase in interest in tramadol due to its dual opioid agonist and serotonin/norepinephrine reuptake inhibition. Several recent studies have demonstrated similar efficacy to other opioids with less somnolence and respiratory depression

TREATMENT DRUGS

Tapentadol • Moderate-to-severe analgesia PO 50–100 mg every 4–6 hours. Max dose 700 mg/day • Pregnancy category: C • Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

• Central opioid agonist • Inhibits norepinephrine reuptake

Uses

Moderate-to-severe acute pain Onset

Time to maximum serum concentration is 1.25 hours Duration

PO 4 hours

Metabolism

Hepatic, cytochrome P450 system Adverse Effects

Respiratory depression, sedation, hypotension, seizures, abuse dependence potential, serotonin syndrome, nausea and vomiting, sweating, decrease in appetite

CLINICAL PEARLS

• Has been demonstrated to have lower risks of respiratory depression, dependence, and GI side effects compared to pure opioid agonists • Serotonin syndrome may be precipitated when administered to patients on tricyclic antidepressants, serotonin selective reuptake inhibitors, and serotonin/norepinephrine reuptake inhibitors • 18 times less potent than morphine at the mu opioid receptor

TREATMENT DRUGS

METHADONE • Moderate-to-severe pain IV 2.5 mg every 8 hours • Pregnancy category: C • Breastfeeding: Infant risk is minimal

Mechanism of Action

Synthetic opioid agonist Uses

• Moderate-to-severe pain • Drug detoxification for opioid abuse • Maintenance therapy of opioid abuse • Neuropathic pain (non-FDA labeled use)

Onset

IV <1 minute, PO 30–60 minutes

Duration

IV 4–6 hours, PO 22–48 hours Metabolism Hepatic

Adverse Effects

QT prolongation, life threat arrhythmias (torsades de pointes), bradycardia, hypotension, constipation, nausea and vomiting, dizziness, sedation, respiratory depression

CLINICAL PEARLS

The respiratory depressant effect of methadone occurs later than its analgesic effects and can lead to the potential for an overdose of this medication

ORAL AGENTS FOR TYPE 2 DM Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Metformin (Glucophage®) • PO 1500–2550 mg/day in divided doses • Age 10–16 years: PO 500 mg BID, up to 2000 mg/day in divided doses • Pregnancy risk B • Breastfeeding: Enters breast milk, not recommended

Mechanism of Action

• Decreases hepatic glucose output • Can increase peripheral glucose utilization

Uses

• Type 2 diabetes • Unlabeled use for treatment of polycystic ovarian syndrome • Unlabeled use for preventative therapy against the development of type 2 diabetes

Onset

Days, peak effect within 2 weeks Duration

Half-life 4–9 hours Metabolism

Not metabolized; 90% excreted unchanged in urine (also actively secreted) Adverse Effects

• Metallic taste, nausea, diarrhea, abdominal pain, weakness, lactic acidosis (rare) • Hypoglycemia is uncommon when used as a single agent

CLINICAL PEARLS

• Drug of choice for initial treatment of type 2 diabetes • May cause weight loss • Increased risk of lactic acidosis in patients with – Impaired renal function (serum creatinine >1.5 mg/dL in males or >1.4 mg/dL in females) – Liver failure – Decompensated CHF

– Alcohol abuse – Advanced age (>80 years) Table 1 Oral agents for type 2 DM

• Should be held at least 24–48 hours preoperatively (especially with major surgery, large expected blood loss, or potential for changes in renal function), and not resumed until oral intake and adequate renal function is assured • Should be discontinued prior to contrast administration and should not be restarted until 48 hours after examination • Many combination products exist with other hypoglycemic agents

TREATMENT DRUGS

Sulfonylureas

• Pregnancy risk B/C • Glipizide and glyburide are not secreted in breast milk • Breastfeeding not recommended

Mechanism of Action

• Increases insulin secretion by beta cells in the pancreas, via interaction with ATP sensitive potassium channels • Reduces hepatic glucose output • Increases insulin sensitivity in peripheral tissues

Uses

Hypoglycemic agent for type 2 diabetes Adverse Effects

Hypoglycemia (more common in elderly, renal/hepatic disease), weight gain, dizziness, headache, weakness, disulfiram type reactions with ethanol ingestion

CLINICAL PEARLS

• Considered to have equivalent efficacy to other commonly used agents • As the duration of diabetes increases, there is a loss of beta cell function; this results in decreased efficacy of the drug • Small incidence of cross allergenicity with sulfonamides • Many combination products exist with other hypoglycemic agents

TREATMENT DRUGS

Pioglitazone (Actos®)

• PO 15–45 mg once daily; lower doses in patients with CHF • Pregnancy risk C • Breastfeeding not recommended

Mechanism of Action

• Increases insulin sensitivity of adipose tissue, skeletal muscle, and liver • Requires the presence of insulin for activity, but does not increase pancreatic insulin output

Uses

Hypoglycemic agent in type 2 diabetes Onset

Maximum effect in 6–14 weeks Duration

Half-life 16–24 hours (both parent and metabolites) Metabolism

Hepatic via CYP2C8 and 3A4 to active and inactive metabolites that are excreted mostly into feces, some in urine Adverse Effects

Increases risk of CHF, peripheral edema, weight gain, macular edema, increase in upper respiratory infections, headache, fatigue, increase in transaminases

CLINICAL PEARLS

• Many combination products with other hypoglycemic agents exist • Possible increased risk of bladder cancer with prolonged/high dose use • Caution in hepatic disease • Multiple drug interactions exist

TREATMENT DRUGS

Exenatide (Byetta®), Liraglutide (Victoza®) • Exenatide: SQ 5–10 mg twice daily, 1 hour prior to meals. May need to lower dose or discontinue in renal failure • Liraglutide: SQ 0.6–1.8 mg daily, no adjustment needed for renal/hepatic disease but caution advised • Pregnancy risk C • Breastfeeding caution with exenatide, liraglutide-not advised

Mechanism of Action

• Analogue of incretin hormone GLP-1 (glucagon like peptide)

• Increases glucose dependent insulin production • Decreases glucagon production • Slows gastric emptying

Uses

Hypoglycemic agent for treatment of type 2 diabetes Onset

• Exenatide: Time to peak 1.2 hours • Liraglutide: Time to peak 8–12 hours

Duration

• Exenatide: Half-life 2.4 hours • Liraglutide: Half-life 13 hours Table 2 Newer generation oral agents for type 2 DM (Dipeptidyl Dipeptidase Inhibitors) Metabolism

• Exenatide: Excreted in urine, minimal metabolism • Liraglutide: Metabolized by endopeptidases and dipeptidyl peptidase, some urine/fecal excretion

Adverse Effects

• Nausea, vomiting, slowed gastric emptying, dyspepsia, pancreatitis, headache • Liraglutide has been associated with thyroid c-cell hyperplasia/tumors

CLINICAL PEARLS

• Causes weight loss, somewhat due to GI side effects • Should not be used in patients with gastroparesis • Decreases rate/absorption of some orally administered drugs • Risk of hypoglycemia increases when used with sulfonylureas/insulin secretagogues

TREATMENT DRUGS

Dipeptidyl Dipeptidase Inhibitors • Pregnancy risk B • Breastfeeding-unknown, caution advised

Mechanism of Action

Inhibits dipeptidyl dipeptidase enzyme which is responsible for inactivation/degradation of incretin hormones GLP-1 (glucagon like peptide) and GIP (glucose dependent insulinotropic polypeptide), both of which potentiate insulin synthesis and release by beta cells, as well as decreasing production of glucagon

Uses

Hypoglycemic agent for treatment of type 2 diabetes Adverse Effects

Peripheral edema, headache, nasopharyngitis, hypoglycemia, diarrhea, nausea, constipation, pancreatitis, hypersensitivity reactions

CLINICAL PEARLS

• Unlikely to cause hypoglycemia unless administered during sulfonylurea therapy or with insulin • Many combination products with other hypoglycemic agents • Use with ACE inhibitors increases the risk of angioedema

PRESSOR AGENTS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Epinephrine (Adrenalin®) • Cardiac arrest/bradycardia IV (or intraosseous) 1 mg (pediatric 0.01 mg/kg) repeated every 3–5 minutes • Anaphylaxis 0.3 mg IV, continuous infusion 1–4 mcg/min • Hypotension/bradycardia/bronchodilation IV bolus 2–10 mcg, infusion 2–20 mcg/kg/min (pediatric 0.01–0.1 mcg/kg/min); subcutaneous 0.3 mg, pediatric 0.01 mg/kg • Endotracheal administration is typically 2–2.5 times the IV dose (dilute to 10 mL with normal saline or distilled water) • Pregnancy risk C, breastfeeding unknown

Mechanism of Action

Direct agonist at alpha-1, beta-1, and beta-2 adrenergic receptors, thereby causing stimulation of the myocardium, relaxation of smooth muscles in the bronchial tree, vasodilation in beta-2 predominant vascular beds, vasoconstriction in alpha-1 innervated beds Uses

Pulseless arrest/asystole, pulseless ventricular tachycardia or fibrillation, symptomatic/severe bradycardia, anaphylaxis, bronchodilator, treatment of hypotension/shock, adjunct/vasoconstrictor in local anesthetic solutions, treatment of airway edema, test dosing in neuraxial/regional anesthesia Onset

• IV: Immediate • SC: 5–10 minutes • Inhalation: 1 minute

Duration

• IV: Minutes • SC: 4 hours as a bronchodilator

Metabolism

• Uptake into neurons • Rapidly metabolized via catechol-O methyl transferase and monoamine oxidase in the liver, synaptic clefts, and tissues; inactive metabolites are excreted in the urine Adverse Effects

Tachycardia, palpitations, dysrhythmias, angina, pulmonary edema, cerebral hemorrhage, mesenteric ischemia, tremor, anxiety, restlessness

CLINICAL PEARLS

• Net cardiovascular effects are modulated by volume status and baroreceptor mediated responses • Metabolic effects tend to increase energy substrates and alter insulin mediated response (may induce hypokalemia); results in increased glycogenolysis, glycolysis, glucagon secretion, and lipolysis • A central line should be used for prolonged infusions; severe tissue loss may occur if extravasated • Severe hypertension may result in patients on MAO inhibitors

TREATMENT DRUGS

Norepinephrine (Levophed®) • IV infusion 0.01–3 mcg/kg/min, varies widely • Pregnancy risk C, breastfeeding unknown

Mechanism of Action

• Direct agonist at alpha-1 and beta-1 receptors thereby causing vasoconstriction, enhanced inotropy, and reflex bradycardia (alpha effects predominate) • Net effects are modulated by baroreceptor responses

Uses

Hypotension, shock states (vasodilatory, septic, cardiogenic) Onset

Rapid

Duration

1–2 minutes Metabolism

Hepatic and neuronal via monoamine oxidase and catecholamine o-methyltransferase, to inactive metabolites excreted in the urine Adverse Effects

Dysrhythmias, bradycardia, cardiac, renal and mesenteric ischemia, peripheral hypoperfusion, anxiety, dyspnea

CLINICAL PEARLS

• Endogenous catecholamine that functions as a neurotransmitter in the CNS and periphery and also as a hormone (glycogenolysis, gluconeogenesis) • Consider for use when tachycardia is undesirable • Increased afterload will increase myocardial oxygen consumption • Increases pulmonary vascular resistance • Volume deficits should be corrected prior to, or during, use • Central line should be used if possible, as severe tissue loss may occur if extravasated (phentolamine should be infiltrated into area if it occurs) • Contains metabisulfite preservative • Severe hypertension may result in patients on MAO inhibitors

TREATMENT DRUGS

Phenylephrine (Neo-synephrine®) • IV bolus 50–100 mcg (pediatric 5–20 mcg/kg/dose) • IV infusion 20–50 mcg/min (or 0.1–0.5 mcg/kg/min adult or pediatric) initially, then titrated to response • Pregnancy risk C, caution with breastfeeding

Mechanism of Action

• Direct agonist at alpha-1 adrenergic receptors thereby increasing venous return to the heart, and increasing systemic and pulmonary vascular resistance • Baroreceptor response may lower heart rate

Uses

• Hypotension, shock, septic shock • Nasal decongestant prior to nasal intubation

Onset

IV Immediate Duration

IV: 15–20 minutes for single bolus Metabolism

Hepatic, to inactive metabolites excreted in the urine Adverse Effects

Reflex bradycardia, hypertension, anxiety, restlessness

CLINICAL PEARLS

• Venoconstriction tends to be greater than arterial • Generally does not cause tachycardia/dysrhythmias that may limit the use of other pressor

agents • Nasal spray may be used to prepare the nasal mucosa for intubation to prevent bleeding • May cause tissue injury if extravasated

TREATMENT DRUGS

Ephedrine • IV bolus 5–25 mg • Pediatric IV bolus 0.2–0.3 mg/kg/dose • Pregnancy risk C, breastfeeding unknown

Mechanism of Action

Direct and indirect acting (causes release of endogenous norepinephrine from nerve endings) agonist at alpha-1 and beta-1 receptors; mild beta-2 activity Uses

Hypotension, general or regional anesthesia induced Onset

• IV: Almost immediate • IM:10–20 minutes

Duration

Up to 1 hour Metabolism

Mostly excreted unchanged in urine Adverse Effects

Tachycardia, hypertension, dysrhythmias, angina/chest pain, anxiety, restlessness, tremor, CNS stimulation

CLINICAL PEARLS

• Maintains uterine blood flow in obstetric patients • May also be given IM • Most cardiovascular effects are similar to epinephrine, but ephedrine is less potent and lasts longer • Doses given after the initial bolus tend to have a reduced response, due to tachyphylaxis

TREATMENT DRUGS

Dopamine (Intropin®)

• Adult/pediatric initial IV infusion at 1–5 mcg/kg/min, titrated to response. May increase infusion by 1–5 mcg/kg/min every 10–30 minutes, up to 50 mcg/kg/min • Pregnancy risk C, breastfeeding unknown

Mechanism of Action

• Dose-related agonism at dopaminergic and adrenergic receptors (see later) • Also by indirect action via norepinephrine release from neuronal storage

Uses

Pressor agent/hemodynamic support, shock, low cardiac output after CPB Onset

5 minutes Duration

<10 minutes Metabolism

Hepatic, renal, and in plasma, via monoamine oxidase; 75% to inactive metabolites, 25% to norepinephrine Adverse Effects

Tachycardia, dysrhythmias, palpitations, angina, hypertension, anxiety

CLINICAL PEARLS

• Hypovolemia should be corrected prior to, or during, use • Hemodynamic responses are dose dependent; lower doses augment renal blood flow and urine output (1–5 mcg/kg/min) and continues to be maintained as beta-1 effects begin to predominate (5–15 mcg/kg/min). Doses exceeding 15 mcg/kg/min predominately raise BP by alpha-1 agonism • If the desired response is not achieved at 20–30 mcg/kg/min, consider changing to a more potent agent (epinephrine or norepinephrine) • Contains metabisulfite • Extravasation can produce tissue injury • No clear evidence exists to show that low dose dopamine confers any degree of renal benefit

TREATMENT DRUGS

Dobutamine (Dobutrex®) • Adult/pediatric IV infusion 2–20 mcg/kg/min, titrated to response (maximum 40 mcg/kg/min) • Pregnancy risk B, breastfeeding unknown

Mechanism of Action

• Beta-1 direct agonist, augments contractility and increases heart rate • Mild beta-2 agonism, thereby does not increase SVR and maintains renal blood flow

Uses

Positive inotropic agent used in low cardiac output states, cardiogenic shock, CHF, weaning from CPB Onset

Minutes

Duration

Peak effect in 10–20 minutes. Rapidly metabolized so constant infusion required Metabolism

Hepatic/tissue metabolism to inactive metabolites excreted in urine Adverse Effects

Tachycardia, dysrhythmias, angina or non specific chest pain

CLINICAL PEARLS

• Contains metabisulfite • May be ineffective in, or contraindicated for, patients with aortic stenosis or IHSS • May exacerbate preexisting dysrhythmias • Used as a diagnostic agent in stress echocardiography • May be used for cardiac decompensation in sepsis when BP is adequate

TREATMENT DRUGS

Milrinone

• IV 0.375–0.75 mcg/kg/min infusion, titrated to hemodynamic response. A loading dose may be given in patients with adequate blood pressure (50 mcg/kg over 10 minutes) • Pregnancy risk C, breastfeeding unknown

Mechanism of Action

• Phosphodiesterase inhibitor that increases intracellular cAMP levels thereby causing inotropy and vasodilation with little chronotropic action • Selective for cardiac and vascular tissue, increases intracellular cAMP levels, has inotropic and vasodilator activity with little chronotropic action Uses

Short-term hemodynamic support in acute or refractory CHF, cor pulmonale, decreased cardiac output states associated with cardiac surgery

Onset

5–15 minutes Duration

Half-life 2.5 hours. Markedly prolonged half-life in renal failure (>20 hours) Metabolism

• Excreted/actively secreted by the kidney (85%); doses need to be adjusted for renal insufficiency (CrCl <50 mL/min) • Hepatic metabolism (12%)

Adverse Effects

Dysrhythmia (including ventricular tachycardia and ventricular fibrillation), cardiac ischemia, hypotension, hepatotoxicity; thrombocytopenia (rare)

CLINICAL PEARLS

• Lacks activity at adrenergic receptors, thereby it is effective in patients with down regulation of beta receptors due to chronic heart failure, or in patients on beta blockers • Tachyphylaxis does not occur • Normal potassium and magnesium levels should be maintained

TREATMENT DRUGS

Isoproterenol (Isuprel®) • IV bolus 20–60 mcg, IV infusion-2–10 mcg/min, titrated to patient response • Pediatric IV infusion 0.05–2 mcg/kg/min • Pregnancy risk C, breastfeeding unknown

Mechanism of Action

• Direct agonist at beta-1 and beta-2 receptors, thereby increasing chronotropy, inotropy, dromotropy, vasodilation, and bronchodilation

Uses

Bradydysrhythmias, AV nodal blockade, refractory Torsades de Pointes, chronotropy in heart transplant recipients Onset

Immediate Duration

10–15 minutes Metabolism

Rapidly conjugated in hepatic and pulmonary tissues; excreted in urine Adverse Effects

Tachycardia, tachydysrhythmias, hypotension, cardiac ischemia due to increased 02 demand, restlessness, tremor, hypokalemia

CLINICAL PEARLS

• Use in ACLS is largely supplanted by other catecholamines and electrical pacing • Not commonly used as a bronchodilator • May terminate Torsades associated with a prolonged QT interval and bradycardia, or druginduced with a prolonged QT interval

PROTON PUMP INHIBITORS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Esomeprazole Magnesium and Esomeprazole Sodium (IV) (Nexium®) • PO 20–40 mg once daily. Capsule may be emptied and pellets used via gastric tube • IV (sodium salt) 20–40 mg once daily • Pediatric—varies by age, weight, and indication • Pregnancy Category: B • Breastfeeding not recommended

Mechanism of Action

Binds irreversibly to and inhibits H+/K+ ATPase enzyme on parietal cells; inhibits “proton pump" and gastric acidity. This is the terminal step of gastric acid production and is irreversible; therefore, capable of inhibiting close to 100% of gastric acid secretion Uses

• Peptic ulcer disease • Reduction of gastric acid production perioperatively • Stress ulcer prophylaxis • Erosive esophagitis and gastroesophageal reflux disease • NSAID induced gastropathy • Prophylaxis for GI bleeding • Acid hypersecretion syndromes

Onset

1–2 hours Duration

Maintains stomach pH above 4 for 17 hours Metabolism

Hepatic CY P450 enzymes (2C19), some 3A4. Inactive metabolites excreted in urine. Reduction of dose required in severe hepatic disease but not renal failure Adverse Effects

Headache, diarrhea, flatulence, nausea, myopathy, increased risk of pneumonia in critically ill patients, bone fractures with chronic use

CLINICAL PEARLS

• May take morning of or evening before surgery • Inhibits metabolism of other drugs by 2C19. May reduce effectiveness of clopidogrel; may increase INR in patients on warfarin • Possible effects on calcium and vitamin B12 absorption • Sodium salt available for IV use • Esomeprazole is the S-enantiomer of omeprazole

TREATMENT DRUGS

Omeprazole (Prilosec®) • PO 20–40 mg once daily. Available as a liquid (suspension) • No parenteral form available • Pediatric—varies by weight. ≥20 kg: 20 mg once daily • Pregnancy Category: C • Breastfeeding not recommended

Mechanism of Action

Binds irreversibly to and inhibits H+/K+ ATPase enzyme on parietal cells; inhibits “proton pump" and gastric acidity. This is the terminal step of gastric acid production and is irreversible; therefore, capable of inhibiting close to 100% of gastric acid secretion Uses

• Peptic ulcer disease • Reduction of gastric acid production perioperatively • Stress ulcer prophylaxis • Erosive esophagitis and gastroesophageal reflux disease • NSAID induced gastropathy • Prophylaxis for GI bleeding • Acid hypersecretion syndromes

Onset

1–2 hours Duration

A stomach pH of 3 or higher is maintained 50–60% of the time during a 24 hour period Metabolism

Hepatic CYP 450 enzymes (2C19). Several inactive metabolites excreted in urine. Dose reduction required in severe hepatic disease but not renal failure, and in patients of Asian origin Adverse Effects

Headache, diarrhea, flatulence, nausea, myopathy, increased risk of pneumonia in critically

ill patients, bone fractures with chronic use

CLINICAL PEARLS

• May take morning of or evening before surgery • Inhibits metabolism of other drugs by 2C19. May reduce effectiveness of clopidogrel; may increase INR in patients on warfarin • Possible effects on calcium and vitamin B12 absorption

TREATMENT DRUGS

Pantoprazole (Protonix®) • Adult PO 40–80 mg once daily. Liquid suspension available • Pediatric (age ≥5) PO 20–40 mg once daily • Adult IV 40–80 mg once daily • Pregnancy Category: B • Breastfeeding not recommended

Mechanism of Action

Binds irreversibly to and inhibits H+/K+ ATPase enzyme on parietal cells; inhibits “proton pump" and gastric acidity. This is the terminal step of gastric acid production and is irreversible; therefore, capable of inhibiting close to 100% of gastric acid secretion Uses

• Peptic ulcer disease • Reduction of gastric acid production perioperatively • Stress ulcer prophylaxis • Erosive esophagitis and gastroesophageal reflux disease • NSAID induced gastropathy • Prophylaxis for GI bleeding • Acid hypersecretion syndromes

Onset

• IV 15–30 minutes • PO 2.5 hours

Duration

• IV 24 hours • PO-acid suppression lasts for 7 additional days after dosing for 7 days

Metabolism

Hepatic-CYP 2C19, secondarily CYP 3A4, to inactive metabolites. No dosage adjustments needed in hepatic or renal insufficiency

Adverse Effects

Headache, diarrhea, flatulence, nausea, myopathy, increased risk of pneumonia in critically ill patients, bone fractures with chronic use. May elevate hepatic transaminases

CLINICAL PEARLS

• May give false positive urine test for marijuana (THC) • May interfere with activation of clopidogrel and interfere with other drugs metabolized by 2C19; may increase INR in patients on warfarin • May decrease absorption of calcium and vitamin B12 with chronic use • May take morning of or evening before surgery

TREATMENT DRUGS

Lansoprazole (Prevacid®) and Dexlansoprazole (Kapidex®) • PO 15–30 mg PO once daily. Granules from capsule may be administered via gastric tube (Dexlansoprazole PO dosing 30–60 mg once daily) • No IV form available • Pediatric—varies by age/weight • Pregnancy Category: B • Breastfeeding unknown/not recommended

Mechanism of Action

Binds irreversibly to and inhibits H+/K+ ATPase enzyme on parietal cells; inhibits “proton pump" and gastric acidity. This is the terminal step of gastric acid production and is irreversible; therefore, capable of inhibiting close to 100% of gastric acid secretion Uses

• Peptic ulcer disease • Reduction of gastric acid production perioperatively • Stress ulcer prophylaxis • Erosive esophagitis and gastroesophageal reflux disease • NSAID induced gastropathy • Prophylaxis for GI bleeding • Acid hypersecretion syndromes

Onset

2 hours

Duration 24 hours

Metabolism

• Converted to active form in the stomach • Hepatic metabolism to inactive metabolites via CYP2C19, 2/3rd excreted in bile • Dexlansoprazole inactive metabolites excreted 50:50 renal/fecal • Dosage adjustment may be required for severe hepatic disease. No changes required for renal insufficiency Adverse Effects

Abdominal pain, constipation, diarrhea, nausea, pancreatitis, headache, myopathy, bone fractures with chronic use

CLINICAL PEARLS

• May interfere with activation of clopidogrel and other drugs metabolized by 2C19; may increase INR in patients on warfarin • May interfere with absorption of calcium and vitamin B12 with chronic use. May take evening before or morning of surgery • Caution with phenylketonurics as oral form contains phenylalanine • Dexlansoprazole is the R-isomer of lansoprazole

TREATMENT DRUGS

Rabeprazole (Aciphex®) • Adult, child >12 years: PO ≥12–20 mg once daily • No suspension available and tablet may not be crushed • No IV form available • Pregnancy Category: B • Breastfeeding unknown

Mechanism of Action

Binds irreversibly to and inhibits H+/K+ ATPase enzyme on parietal cells; inhibits “proton pump" and gastric acidity. This is the terminal step of gastric acid production and is irreversible; therefore, capable of inhibiting close to 100% of gastric acid secretion Onset

1 hour

Duration 24 hours

Metabolism

Hepatic via CYP2C19, and 3A, to inactive metabolites excreted in urine (90%). Possible need to reduce dose in severe hepatic disease. No reduction in dose required for renal failure Adverse Effects

Abdominal pain, constipation, diarrhea, flatulence, nausea, altered taste, headache, myopathy, bone fractures with chronic use, hyperammonemia

CLINICAL PEARLS

• May interfere with activation of clopidogrel, and other drugs inactivated by CYP2C19. Monitor INR in patients on warfarin • May interfere with absorption of calcium and vitamin B12 with chronic use • May take morning of or evening before surgery

PULMONARY GASES TREATMENT DRUGS

Nitric Oxide

Usual Dosing—20 parts per million for up to 14 days or until resolution of oxygen desaturation. Pregnancy category: C. Breastfeeding: Infant risk cannot be ruled out. Mechanism of Action

Nitric oxide is a smooth muscle relaxant caused by activating guanylate synthase resulting in synthesis of cyclic guanosine 3’5’-monophosphate Uses

FDA approved – neonatal respiratory failure – perinatal hypoxia-pulmonary hypertension. Non FDA label – ARDS, pulmonary hypertension – CV surgery, CHF, primary pulmonary hypertension, high altitude pulmonary edema, right sided heart failure Onset

Immediate Duration

Half life 2–6 seconds Metabolism

Inhalational

Adverse Effects

Hypotension, acute lung injury, atelectasis, pulmonary edema, pulmonary hemorrhage, pulmonary toxicity, stridor, intracranial hemorrhage, methemoglobinemia, hematuria, hyperglycemia

CLINICAL PEARLS

With the use of nitric oxide, there is the chance of methemoglobinemia occurring especially with higher doses. Nitric oxide should be titrated rather than abruptly discontinued as this can lead to a worsening of oxygenation and increase pulmonary artery pressure.

TREATMENT DRUGS Xenon

Usual Dosing—Pregnancy category and Breastfeeding: Not yet categorized Mechanism of Action

Is 54th element on periodic table. It works as an anesthetic by inhibiting the plasma membrane calcium pump. It has been found that xenon inhibits the nociceptive responsiveness of spinal dorsal horn neurons. Uses

General anesthetic, use in lasers, flash bulbs, lamps. Onset

Rapid

Duration Rapid

Metabolism

Inhalational

Adverse Effects

Respiratory depression, may get a diffusion hypoxia, increased cerebral blood flow, increased intracranial pressure, cost

CLINICAL PEARLS

Xenon has been labeled the “ideal anesthetic gas” because of its minimal disturbance of hemodynamics, rapid induction and awakening times, it is non pungent, and it produces unconsciousness with analgesia. The MAC of Xenon is 60–70% and therefore an acceptable level of inspired concentration can be used.

TREATMENT DRUGS

Heliox Usual Dosing—70% helium + 30% Oxygen. Pregnancy category and Breastfeeding: Not yet categorized Mechanism of Action

Is a mixture of 30% oxygen and 70% helium. Heliox has a lower density than air and therefore causes less resistance because it causes a higher probability of laminar flow than turbulent flow. Uses

Acute asthma, upper airway obstruction from tumors, vocal cord dysfunction, croup, chronic obstructive pulmonary disease.

Onset

Rapid

Duration Rapid

Metabolism

Inhalational

Adverse Effects

Improper delivery by someone not familiar with delivery device, anoxia, barotrauma, hypocarbia, hypothermia

CLINICAL PEARLS

Heliox seems to be most beneficial in patients in the upper and middle airways where turbulent flow can be decreased in favor of laminar flow. In the small airways, turbulent flow predominates and laminar flow is not possible, and therefore helix does not help decrease resistance for this usage.

REVERSAL AGENTS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Edrophonium • Usual Dosing – Reversal of neuromuscular blockade: IV 10 mg may be repeated up to 40 mg in adults – Pediatric neuromuscular blockade reversal: IV 0.15–0.2 mg/kg – Pregnancy category: C – Breastfeeding: Infant risk cannot be ruled out Mechanism of Action

• Reversibly binds to acetylcholinesterase (AChE) enzyme and prevents the breakdown of Ach • Acetylcholine neurotransmitter functions at both nicotinic and muscarinic receptors. AChE is located at the neuromuscular junction, sympathetic, and parasympathetic nervous system ganglions, and central nervous system. It is responsible for the breakdown of acetylcholine into choline and acetate • Neuromuscular blocking drugs (NMBD) compete with Ach at the nicotinic Ach receptors and prevent neurotransmission/muscle contraction. Their action is terminated by diffusion away from the NMJ and metabolism by the liver, kidneys, bile, or pseudocholinesterase. When faster recovery is desired, anticholinesterases can be administered to block Ach breakdown. By increasing Ach levels, more is available to compete with NMBD at nicotinic Ach receptors and neurotransmission/muscle contraction can be re-established • Myasthenia gravis (MG) is an autoimmune disease where abnormal production of antibodies results in blocking and destroying nicotinic Ach receptors (prevents normal Ach neurotransmitter binding and muscle contraction). Anticholinesterases increase Ach levels to compete with the antibodies and compensate for the decrease in available Ach receptors Uses

• Reversal of muscle blockade by nondepolarizing neuromuscular blockers • Diagnosis and treatment of myasthenia gravis (MG)

Onset

1–2 minutes Duration

1–2 hours

Metabolism

Renal excretion

Adverse Effects

The parasympathetic nervous system releases Ach neurotransmitter at both the pre-ganglionic (muscarnic and nicotinic receptors) and post-ganglionic junctions (muscarinic receptors). Therefore, at the PNS, anticholinesterases result in bradycardia, increase in respiratory secretions and bronchoconstriction, and GI tract peristaltic activity and glandular secretions (requires co-administration with anti-muscarinics to off-set these undesirable effects)

CLINICAL PEARLS

• Edrophonium is a reversal agent with the quickest onset of action (1–2 minutes). Useful to differentiate cholinergic crisis from MG weakness (quick onset and offset). When used to reverse NMBD, it should be co-administered with atropine (similar onset time) or glycopyrrolate prior to administration • May have less muscarinic effects than neostigmine • Lipid insoluble due to its quaternary ammonium group and does not cross the blood brain barrier; thus ineffective in treating delirium or Alzheimer’s

TREATMENT DRUGS

Physostigmine • Usual dosing change to – IV 2 mg for reversal of central anticholinergic syndrome – Pregnancy category: C – Breastfeeding: Infant risk cannot be ruled out

Mechanism of Action

• Reversibly binds to acetylcholinesterase (AChE) enzyme and prevents the breakdown of Ach • Lacks a quaternary ammonium group and is lipid soluble, allowing it to cross the blood brain barrier • Anticholinergic syndrome. Antihistamine, antiparkinson, antipsychotic, antispasmodic, certain plants, TCA’s, and ophthalmic drugs can compete with Ach at muscarinic Ach receptors.“Dry as a bone, red as a beet, hot as a hare, blind as a bat, mad as a hatter, stuffed as a pipe;" refers to the inhibition of sweating, flushing, mydriasis, delirium, and ileus that can result. If the diagnosis is incorrect, it will result in cholinergic toxicity • Postoperative delirium. Elevated serum anticholinergic activity in patients with delirium suggests that cholinergic medications (or anticholinesterases) may be useful in treatment

Uses

• Treatment of central anticholinergic syndrome • Postoperative delirium • Prevention of postoperative shivering

Onset

3–8 minutes Duration

30–60 minutes Metabolism

Hydrolysis by plasma esterases and cytochrome P450 Adverse Effects

Salivation, lacrimation, Increased GI peristalsis, bronchoconstriction, pupillary constriction, bradycardia

CLINICAL PEARLS

Physostigmine is able to cross the blood brain barrier making it very useful to reversal effects of central anticholinergic syndrome, but at the same time, limits its use as a reversal agent. The other three reversal agents do not cross the blood brain barrier and do not have the central side effects that physostigmine has

TREATMENT DRUGS

Pyridostigmine • Usual dosing change to – PO 60 mg TID up to 120 mg q3hours – Pregnancy category: C – Breastfeeding: Infant risk is minimal

Mechanism of Action

• Reversibly binds to acetylcholinesterase (AChE) enzyme and prevents the breakdown of Ach • MG is an autoimmune disease where abnormal production of antibodies results in blocking and destroying nicotinic Ach receptors (prevents normal Ach neurotransmitter binding and muscle contraction). Anticholinesterases are utilized for symptomatic treatment by increasing Ach levels to compete with the antibodies and compensate for the decrease in available Ach receptors

Uses

• Treatment of myasthenia gravis

Onset

15–20 minutes Duration

1–2 hours

Metabolism

Renal excretion

Adverse Effects

Salivation, lacrimation, increased GI peristalsis, bronchoconstriction, pupillary constriction, bradycardia

CLINICAL PEARLS

Pyridostigmine has lost its popularity as a reversal agent for neuromuscular blockade due to its long onset of action compared to neostigmine and edrophonium. For patients with a weak residual block, there is a minimal difference between return to normal function with or without pyridostigmine

TREATMENT DRUGS

Neostigmine • Usual dosing – Reversal of neuromuscular blockade: IV 40 mcg/kg; should not exceed 5 mg total except in exceptional cases – Pregnancy category: C – Breastfeeding: Infant risk cannot be ruled out Mechanism of Action

• Reversibly binds to acetylcholinesterase (AChE) enzyme and prevents the breakdown of Ach • Lipid insoluble due to quaternary ammonium group; does not cross the blood brain barrier • Acetylcholine neurotransmitter functions at both nicotinic and muscarinic receptors. AChE is located at the neuromuscular junction, sympathetic, and parasympathetic nervous system ganglions, and central nervous system. It is responsible for the breakdown of acetylcholine into choline and acetate • Neuromuscular blocking drugs (NMBD) compete with Ach at the nicotinic Ach receptors and prevent neurotransmission/muscle contraction. Their action is terminated by diffusion away from the NMJ and metabolism by the liver, kidneys, bile, or pseudocholinesterase. When faster recovery is desired, anticholinesterases can be administered to block Ach breakdown. By increasing Ach levels, more is available to compete with NMBD at nicotinic Ach receptors and neurotransmission/muscle contraction can be re-established Uses

• Most commonly utilized for reversal of muscle blockade by non depolarizing agents • Treatment of myasthenia gravis

Onset

7–11 minutes Duration

1–2 hours

Metabolism

Renal excretion

Adverse Effects

• Salivation, lacrimation, increase GI peristalsis, bronchoconstriction, pupillary constriction, bradycardia • Prolongation of succinylcholine. AChEs have variable inhibitory effects on pseudocholinesterase (plasma enzyme that metabolizes succinylcholine) as well as increase motor end plate potential by increasing Ach in the NMJ (prevents subsequent action potentials and muscle contraction)

CLINICAL PEARLS

• Neostigmine has a longer onset of action compared to Edrophonium, but is more effective at reversing an intense block. Maximal dose should not exceed 0.07 mg/kg because there is a ceiling effect to the drug • Recommended anticholinergic: glycopyrrolate

THIENOPYRIDINES/ADP INHIBITORS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

MEDICATION • Pregnancy Category: B • Lactation unknown

Table 1 Thienopyridines/ADP inhibitors Mechanism of Action

• Irreversibly (for the 7–10 days lifespan of a platelet) inhibits the ADP receptor on the platelet membrane. The receptor is responsible for activating the glycoprotein IIb–IIIa receptor complex, thus preventing fibrin cross-linking and platelet aggregation • All 3 agents are prodrugs which require activation by cytochromes in situ

Uses

• Acute coronary syndromes/PCI placement • Prevention of stent thrombosis • Post cerebrovascular accident or myocardial infarction • Prevention of thrombosis in peripheral vascular disease

Adverse Effects

Bleeding, bruising, hematoma, rash, pruritus, neutropenia, thrombocytopenia, TTP, nausea, diarrhea

CLINICAL PEARLS

• Contraindicated in patients with active GI or intracranial bleeding • Usually used concurrently with aspirin (dual-platelet therapy) • Bleeding risk is increased in patients on other agents that impair clotting • TTP is a rare complication; usually occurs in first 2 weeks of therapy • Pharmacogenomic variations in CYP2C19, and drugs which inhibit 2C19 (proton pump inhibitors for example) may increase the risk of thrombosis due to inhibition of prodrug conversion • H2 blockers may be considered as alternative GI prophylaxis agents in those at risk • Cardiology consultation is recommended when contemplating holding these agents for elective surgery after coronary stent placement. The ACC/AHA recommends continuing these agents for 4–6 weeks after bare metal stent placement, and at least 12 months after a drug eluting stent is placed. Typically aspirin is still continued unless risk or consequences of bleeding exceed that of stent thrombosis. Clopidogrel should be held at least 5 days prior

to elective surgery, prasugrel at least 7 days; they should then be resumed the day after surgery if appropriate • ASRA guidelines recommend holding clopidogrel for 7 days prior to neuraxial block, 14 days for ticlopidine

VOLATILE ANESTHETICS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

• MAC value at 6% • Pregnancy Category: B

Mechanism of Action

Unknown, fluorinated methyl ethyl ether Uses

• May be used for induction, but not recommended for pediatric induction (less pungent agents are preferred) • Maintenance of anesthesia • Sedation • Status asthmaticus

Onset

Rapid onset of action Duration

Low blood gas solubility (blood:gas partition coefficient 0.45) leads to a short duration once volatile agent is discontinued, even after extended time of administration Metabolism

• Excretion is through lung ventilation • Oxidative metabolism 0.02% by cytochrome p450 enzymes

Adverse Effects

• Increased heart rate, hypotension • Degraded by hydrated carbon dioxide absorbent to carbon monoxide (produces the highest carbon monoxide production of the volatile anesthetics) • Decreased cerebral metabolic activity; increased cerebral blood flow, intracranial pressure; and can produce isoelectric EEG • Pungent to airways • Increased respiratory rate; decrease tidal volume, overall minute ventilation

CLINICAL PEARLS

• Least potent volatile anesthetic; rapid titratibility due to low solubility • Desflurane will boil at OR temperatures and a heated pressurized vaporizer is necessary for

administration • May cause a sympathetic stimulation when rapidly increased beyond 1 MAC concentration

TREATMENT DRUGS

Sevoflurane

• MAC value at 2.2% • Pregnancy Category: B

Mechanism of Action

Unknown, fluorinated methyl isopropyl ether Uses

• Induction, less pungent than desflurane • Maintenance of anesthesia • Sedation • Status asthmaticus

Onset

Rapid onset of action Duration

Low blood gas solubility (blood:gas partition coefficient of 0.69). This ensures a short duration even after extended periods of administration Metabolism

• Excretion is through lung ventilation • Biodegradation is responsible for ~3–5% • Does not form carbon monoxide

Adverse Effects

• Hypotension, little change in heart rate, mild decrease in cardiac output • Compound A formation is a nephrotoxic by-product that is formed from exposure to warm, moist soda lime • Decreased cerebral metabolic rate; increased cerebral blood flow, intracranial pressure; can produce isoelectric EEG • Increase respiratory rate; decreased tidal volume, overall minute ventilation

CLINICAL PEARLS

• Unlike desflurane, the chemical properties allow for delivery via a conventional vaporizer • Non-pungent and causes the least degree of airway irritation, therefore making it suitable for inhalation induction • Not degraded to acetyl halide metabolites and therefore does not produce immune mediated

hepatotoxicity like the rest of the volatile agents do

TREATMENT DRUGS

Isoflurane • MAC value at 1.2% • Pregnancy Category: C

Mechanism of Action

Unknown, halogenated methyl ethyl ether Uses

• Induction, less pungent than desflurane • Maintenance of anesthesia • Sedation • Status asthmaticus

Onset

• Immediate onset; slower compared to sevoflurane and desflurane

Duration

Intermediate duration. The blood:gas partition coefficient is 1.4, making it a more soluble agent and therefore has a longer duration of action than sevoflurane or desflurane Metabolism

• Excretion via lung ventilation • Undergoes some oxidative metabolism (0.2%) by liver cytochrome p450 producing acetylated liver proteins • Less incidence of hepatotoxicity than with halothane, but occurs at a greater incidence than with desflurane

Adverse Effects

• Hypotension, increased heart rate, minimal overall change in cardiac output, direct myocardial depressant • Will produce an isoelectric EEG; decrease cerebral metabolic activity; and increase cerebral blood flow, ICP • Increases respiratory rate; decreases tidal volume and overall minute ventilation

CLINICAL PEARLS

Isoflurane, like the rest of the volatile agents, produces coronary vasodilation, and therefore was thought to be prone to coronary artery steal phenomenon. This has been found to not be clinically relevant

TREATMENT DRUGS

Halothane • MAC value at 0.76% • Pregnancy Category: C

Mechanism of Action

Unknown mechanism of action, halogenated alkane derivative Uses

• Induction • Maintenance of anesthesia • Sedation • Status asthmaticus

Onset

Intermediate onset as compared to desflurane and sevoflurane Duration

Intermediate duration compared to desflurane and sevoflurane. The blood:gas partition coefficient is 2.5 Metabolism

• 15–20% undergoes metabolism. When ample oxygen is available, halothane undergoes oxidation by P450 enzymes, but reductive metabolism when PO2 is low • Halothane hepatitis can occur by 2 mechanisms—immune mediated, or changes in hepatic blood flow that impair hepatic oxygenation Adverse Effects

• Hypotension, bradycardia, direct myocardial depression, and overall decrease in cardiac output. Produces arrhythmogenic potential when used with epinephrine • Increased cerebral blood flow that requires hyperventilation prior to the initiation of halothane anesthetic, ICP; decreased cerebral oxygen requirement; burst suppression does not occur until concentrations >4 MAC are administered

CLINICAL PEARLS

Less pungent volatile anesthetic and therefore useful for inhalational induction. This volatile agent is not used very often anymore in favor of the newer volatile agents

TREATMENT DRUGS

Nitrous Oxide

• MAC value >100%, which translates to nitrous oxide being incapable of providing general anesthesia at atmospheric pressures • Pregnancy Category: C

Mechanism of Action

Unknown mechanism of action Uses

• Assist with mask induction (non-pungent, odorless) • Supplements anesthetic technique for maintenance or sedation • Analgesia

Onset

Rapid

Duration

Very short duration secondary to low blood:gas partition coefficient of 0.46 Metabolism

• Only 0.004% is metabolized via reductive metabolism to nitrogen

Adverse Effects

• Minimal change to heart rate, BP, and cardiac output secondary to the increase in sympathetic nervous system activity caused by this drug • Increases ICP and cerebral blood flow; decreases cerebral metabolic activity • Increase in respiratory rate; decrease in tidal volume and overall decrease in minute ventilation

CLINICAL PEARLS

• Odorless gas • Most commonly administered as an adjunct to the anesthetic, due to the fact that 1 MAC cannot be achieved at atmospheric pressure • Inactivates B12 • Addition of this drug may cause clonus or opisthotonus

WARFARIN/LOW MOLECULAR WEIGHT HEPARINS/FXA INHIBITORS Alan J. Kover, MD, PharmD

TREATMENT DRUGS

Warfarin (Coumadin®, Jantoven®) • Initial dose PO 5–10 mg daily for 2 days, then maintenance doses are adjusted per PT/INR testing, (usually 5–10 mg once daily) • Wide variation in dosing exists – Consider lower initial doses in patients with hepatic impairment, CHF, malnutrition, the elderly, debilitation, or variation in metabolizing enzymes – Consider higher doses in patients taking metabolizing enzyme inducers – Pediatric (unlabeled use) loading dose PO 0.2 mg/kg, then 0.09–0.33 mg/kg/day, adjusted per INR. Same dosing considerations as adult – Pregnancy Category: X – Breastfeeding compatible; does not enter breast milk Mechanism of Action

Inhibits hepatic synthesis of vitamin K dependent clotting factors (II, VII, IX, and X) as well as protein C and S, by inhibiting vitamin K epoxide reductase complex (VKORC-1) mediated reactivation of vitamin K Uses

Prevention and treatment of thrombosis and/or embolism Onset

PO 24–72 hours; full effect in 5–7 days Duration

2–5 days half-life; mean 40 hours (highly variable) Metabolism

Hepatic, primarily via CYP2C9 but other microsomal enzymes involved. Metabolites excreted in urine Adverse Effects

Bleeding, GI hemorrhage, hemorrhagic shock, hypersensitivity necrosis/gangrene, purple toe syndrome, joint pain, osteoporosis

CLINICAL PEARLS

reactions,

skin

• Vitamin K and/or fresh frozen plasma (FFP) may be used to antagonize warfarin effects if needed for bleeding or prior to surgical procedures • Perioperative discontinuance of warfarin should occur 3–4 days preoperatively and PT/INR checked • “Bridging" with heparinoids may be considered based upon the indication for anticoagulation, risk of bleeding, and timing of interventions. When instituting or resuming therapy, overlapping of therapy with heparinoids for at least 5–7 days is indicated until a therapeutic INR is obtained (thrombosis may be induced by early depletion of anticoagulant proteins C and S) • Target PT/INR are dictated by the exact indication • Genotypic testing is available for variation in CYP2C9 and for VKORC-1 to assist in dosing • High intake of dietary vitamin K inhibits effects, and infections/antibiotics can alter absorption of vitamin K, thereby altering the response. Many drug and herbal interactions exist. Acute ethanol ingestion decreases warfarin metabolism (increases PT/INR) while chronic use of ethanol increases warfarin metabolism (decreases PT/INR)

TREATMENT DRUGS

Low molecular weight heparin (enoxaparin- Lovenox®, dalteparin-Fragmin®) • Pediatric doses of enoxaparin vary by age/weight • Pregnancy Category: B • Breastfeeding-caution advised

Mechanism of Action

• Binds to antithrombin III and accelerates its inhibition of factor Xa • Relatively little anti-IIa activity compared to unfractionated heparin

Uses

• Deep vein thrombosis prophylaxis and treatment • Pulmonary embolus treatment • Anticoagulation in patients with acute coronary syndromes • Perioperative surgical prophylaxis • Prophylaxis in patients with prolonged immobilization

Onset

• Enoxaparin peak effects within 3–4 hours after SQ injection • Dalteparin peak effects within 1–2 hours after SQ injection

Duration

Dose dependent, anti-Xa activity around 12 hours (enoxaparin 40 mg) Metabolism

• Hepatic, to smaller fragments with little activity that are excreted via the kidneys; some

excreted unchanged • Doses need adjustment with renal insufficiency (CrCl <30 mL/min), possibly in morbid obesity See Table Adverse Effects

Bleeding, thrombocytopenia-both immune complex mediated and non immunologically mediated (less common than with unfractionated heparin), fever, bruising, local reactions at injection sites, hypersensitivity reactions, hyperkalemia

CLINICAL PEARLS

• Refer to ASRA guidelines when contemplating neuraxial or regional anesthesia on patients who are on, or will receive, these agents • Should not be used in patients with a history of heparin induced, immune complex mediated thrombocytopenia, or those allergic to pork, or with active major bleeding • Monitoring of PT, aPTT, or INR are not necessary. However, platelet count and renal function should be monitored • Anti-Xa levels may be monitored in some patients • Should be administered SQ; some patients may receive IV administration during acute myocardial infarction or PCI. Do not administer IM • For enoxaparin, 1 mg = 100 units of anti-Xa activity

TREATMENT DRUGS

Vitamin K • Reversal of anticoagulation PO/IV 0.25–10 mg with increasing doses for more rapid reversal • Pregnancy Category: C • Breastfeeding: Infant risk is minimal

Mechanism of Action

• Vitamin K is necessary for the synthesis of coagulation factors II, VII, IX, and X as well as protein C and S • Warfarin inhibits hepatic synthesis of these vitamin K dependent clotting factors by inhibiting vitamin K epoxide reductase complex (VKORC-1) mediated reactivation of vitamin K

Uses

• Reversal of anticoagulants • Bone preservation • Myelodysplastic syndrome

Onset

1–2 hours, peak time 3–6 hours Duration

Half-life 24 hours Metabolism Hepatic

Adverse Effects

Hemolytic anemia, hyperbilirubinemia in premature infants

CLINICAL PEARLS

• Vitamin K is an effective agent to reverse the effects of warfarin; however, if immediate reversal is necessary, then fresh frozen plasma (FFP) should be considered • The use of vitamin K to increase bone formation is still investigational but appears promising based on recent literature

APPENDIX FOR OXYGEN ANALYZER This checkout, or a reasonable equivalent, should be conducted before administration of anesthesia. These recommendations are only valid for an anesthesia system that conforms to current and relevant standards and includes an ascending bellows ventilator and at least the following monitors: Capnograph, pulse oximeter, oxygen analyzer, respiratory volume monitor (spirometer), and breathing system pressure monitor with high- and low-pressure alarms. This is a guideline which users are encouraged to modify to accommodate differences in equipment design and variations in local clinical practice. Such local modifications should have appropriate peer review. Users should refer to the operator’s manual for the manufacturer’s specific procedures and precautions, especially the manufacturer’s lowpressure leak test (step #5). Emergency Ventilation Equipment * 1. Verify Backup Ventilation Equipment is Available and Functioning High Pressure System * 2. CheckOxygenCylinder Supply a. Open O2 cylinder and verify at least half full (about 1000 psi).

b. Close cylinder. * 3. Check Central Pipeline Supplies a. Check that hoses are connected and pipeline gauges read about 50 psi. Low Pressure System * 4. Check Initial Status of Low Pressure System a. Close flow control valves and turn vaporizers off. b. Check fill level and tighten vaporizers’ filler caps. * 5. Perform Leak Check of Machine Low Pressure System a. Verify that the machine master switch and flow control valves are OFF. b. Attach “Suction Bulb” to common fresh gas outlet. c. Squeeze bulb repeatedly until fully collapsed. d. Verify bulb stays fully collapsed for at least 10 seconds. e. Open one vaporizer at a time and repeat ‘c’ and ‘d’ as above. f. Remove suction bulb, and reconnect fresh gas hose. * 6. Turn on Machine Master Switch and all other necessary electrical equipment. * 7. Test Flowmeters a. Adjust flow of all gases through their full range, checking for smooth operation of floats and undamaged flowtubes. b. Attempt to create a hypoxic O2/N2O mixture and verify correct changes in flow and/or

alarm.

Scavenging System

* 8. Adjust and Check Scavenging System

a. Ensure proper connections between the scavenging system and both APL (pop-oft) valve and ventilator relief valve. b. Adjust waste gas vacuum (if possible).

c. Fully open APL valve and occlude Y-piece. d. With minimum O2 flow, allow scavenger reservoir bag to collapse completely and verify that absorber pressure gauge reads about zero.

e. With the O2 flush activated allow the scavenger reservoir bag to distend fully, and then

verify that absorber pressure gauge reads <10 cm H2O. Breathing System * 9. Calibrate O2 Monitor

a. Ensure monitor reads 21% in room air. b. Verify low O2 alarm is enabled and functioning.

c. Reinstall sensor in circuit and flush breathing system with O2.

d. Verify that monitor now reads greater than 90%. 10. Check Initial Status of Breathing System a. Set selector switch to “Bag” mode. b. Check that breathing circuit is complete, undamaged, and unobstructed. c. Verify that CO2 absorbent is adequate.

d. Install breathing circuit accessory equipment (e.g., humidifier, PEEP valve) to be used during the case. 11. Perform Leak Check of the Breathing System a. Set all gas flows to zero (or minimum).

b. Close APL (pop-off) valve and occlude Y-piece. c. Pressurize breathing system to about 30 cm H2O with O2 flush.

d. Ensure that pressure remains fixed for at least 10 seconds.

e. Open APL (pop-off) valve and ensure that pressure decreases. Manual and Automatic Ventilation Systems

12. Test Ventilation Systems and Unidirectional Valves a. Place a second breathing bag on Y-piece.

b. Set appropriate ventilator parameters for next patient.

c. Switch to automatic ventilation (Ventilator) mode. d. Fill bellows and breathing bag with O2 flush and then turn ventilator ON.

e. Set O2 flow to minimum, other gas flows to zero.

f. Verify that during inspiration bellows delivers appropriate tidal volume and that during expiration bellows fills completely. g. Set fresh gas flow to about 5 L/min.

h. Verify that the ventilator bellows and simulated lungs fill and empty appropriately without sustained pressure at end expiration. i. Check for proper action of unidirectional valves.

j. Exercise breathing circuit accessories to ensure proper function.

k. Turn ventilator OFF and switch to manual ventilation (Bag/APL) mode. I. Ventilate manually and assure inflation and deflation of artificial lungs and appropriate feel of system resistance and compliance. m. Remove second breathing bag from Y-piece. Monitors 13. Check, Calibrate, and/or Set Alarm Limits of all Monitors Capnometer Pulse Oximeter Oxygen Analyzer Respiratory Volume Monitor (Spirometer) Pressure Monitor with High and Low Airway Alarms Final Position 14. Check Final Status of Machine a. Vaporizers off b. AFL valve open c. Selector switch to “Bag” d. All flowmeters to zero e. Patient suction level adequate f. Breathing system ready to use * If an anesthesia provider uses the same machine in successive cases, these steps need not be repeated or may be abbreviated after the initial checkout.

INDEX Note: Page numbers followed by f and t indicates figure and table respectively. A

A-a gradient, 36, 387 (See also Alveolar–arterial gradient and ratio) The Abbreviated Donor History Questionnaire (ADHQ), 887 Abdominal aortic aneurysms (AAAs), 4–6 anesthetic goals/guiding principles, 4 intraoperative care anesthesia, choice of, 5 extubation/emergence, 5 induction/airway management, 5 maintenance, 5 monitoring, 5 postoperative care, 5 preoperative assessment, 4 preoperative preparation, 5 rupture, 6–7 (See also Ruptured abdominal aortic aneurysms (rAAA)) statin therapy and, 648 Abdominal binder, in post-dural puncture headache, 685 Abdominal free air, and chest x-ray, 221 Abdominoperineal resection (APR), 8–9 Abilify. See Aripiprazole Abscess epidural, 372–373 intracranial, 445 peritonsillar, 784–785 retropharyngeal, 784–785 Absorbents, carbon dioxide, 158–159 Absorption atelectasis, 833 ACCORD trial, 462 Accupril. See Quinapril ACE inhibitors (ACE-I), 57 in angina, 226 in diabetes mellitus, 328 in peripheral vascular disease, 652 in Raynaud’s phenomenon, 762 Acetaminophen, 115, 388, 755, 1035 in breastfeeding mothers, 510 Acetylcholine (ACh), 600

Acetylcholinesterase, 335 Achalasia, and chest x-ray, 221 Acid–base buffering systems, 150 Acids, 150. See also Buffering systems Aciphex. See Rabeprazole ACLS anesthetic management, 12–13 Acromegaly, 14–15, 336 anesthetic goals/guiding principles, 14 intraoperative care, 15 postoperative care, 15 preoperative assessment, 14–15 preoperative preparation, 15 Actos. See Pioglitazone Acute adrenal insufficiency, 16–17 Acute dystonic reactions (ADRs), 852 Acute kidney injury (AKI), 496, 700, 768–769 intrarenal, 496–497, 769 postrenal, 496, 704–705, 769 prerenal, 496, 718–719, 769 The Acute Kidney Injury Network, AKI classification by, 700 Acute lung injury (ALI), 20, 602 and development of IPS, 808 Acute normovolemic hemodilution (ANH), 18–19 advantages of, 18 blood amount to be collected in, 19 collection process, 19 considerations in, 19 contraindications to, 18 efficacy of, 19 equations related to, 19 goal of, 18 indications for, 18 monitoring during, 18 Acute respiratory distress syndrome (ARDS), 20–21, 39, 476, 602 and chest x-ray, 221 exudative phase, 20 fibroproliferative changes in, 20 nonpharmacologic interventions for, 21 pharmacologic interventions for, 21 Acute tubular necrosis (ATN), 340, 496. See also Acute kidney injury (AKI) Adalat. See Nifedipine Addicted anesthesia care provider, 858–859 Addison disease, 34, 284. See also Aldosterone Adenocard. See Adenosine

Adenosine, 974 in atrial tachycardia, 106 ADH therapy, 326 Adjacent-segment disease. See Transitional syndrome Adrenal cortex, angiotensin effect on, 56 Adrenal crisis. See Acute adrenal insufficiency Adrenalectomy, 22–23 anesthetic goals/guiding principles, 22 intraoperative care, 23 laparoscopic, 22 open, 22 anterior approach, 22 posterior approach, 22 thoracoabdominal approach, 22 postoperative care, 23 preoperative assessment, 22 preoperative preparation, 23 Adrenal gland, 34 Adrenalin. See Epinephrine Adrenal medulla, 112 Adrenocorticotropic hormone (ACTH), 284 Advanced cardiac life support (ACLS) anesthetic management, 12–13 for pulseless electrical activity, 752–753 Adverse drug reaction, 554. See also Medication errors Advil. See Ibuprofen Aerobic metabolism, 46 Afibrinogenemia, 398 Afterload, 24–25, 848. See also Wall stress decreased, 25 increased, 24–25 Air collections, in pleural space, 219 Air/gas embolism, 444 Air hunger, 92 Airway compromise, 61 Airway fires, 26–27 prevention of, 26 AKI. See Acute kidney injury (AKI) Alanine aminotransferase, 526 Albumin, 246, 526, 1011. See also Colloids Albuterol, 998 in asthma, 95, 998 Albuterol/ipratropium, 998 Alcohol abuse, 28–29, 828

Alcoholic cardiomyopathy (ACM), 32–33 asymptomatic stage, 32 diagnosis of, 32 in perioperative period, 33 symptomatic stage, 32 treatment of, 32 Alcohol Use Disorders Identification Test (AUDIT), 28, 29 Alcohol withdrawal syndrome (AWS), 29, 30–31 prevention of, 30 treatment of, 30 Aldactone. See Spironolactone Aldomet. See Methyldopa Aldosterone, 34–35, 56 effect on volume and blood pressure, 34 hyperaldosterone state, 34, 35 hypoaldosterone state, 34, 35 secretion of, 34 synthesis of, 34 Aldosteronoma, adrenalectomy for, 22–23 Aleve. See Naproxen Alfentanil, 1037 context-sensitive half-time, 260 Alfuzosin, 1031t Alkaline phosphatase, 526 Allen test, 86, 274 Allogeneic transfusions, 108, 132 Aloxi. See Palonosetron Alpha-2 agonists and cerebral blood flow, 209 and EEG, 357 Alpha-glucosidase inhibitors, in diabetes mellitus, 328 Alpha receptor antagonists, in Raynaud’s phenomenon, 762 Alpha stat management, 654 Altace. See Ramipril Alteplase, in pulmonary embolism, 739 Alveolar–arterial gradient and ratio, 36–37 Alveolar dead space, 314 Alveolar gas equation, 387, 631 Alveolar hypoventilation, 564 Alveolar PO2, 36

Alveolar pressure (PA), 38

Alveoli, 38–39 gas exchange across, 38 size, 38

walls, 38 Amantadine in multiple sclerosis, 578 in Parkinson’s disease, 628 Amaryl. See Glimepiride American Academy of Allergy and Immunology, 520 American Academy of Neurology criteria for clinical diagnosis of brain death, 142 American Association for the Study of Liver Diseases, 434 American Heart Association, ACLS guidelines, 12 American Society for Regional Anesthesia (ASRA), 374 American Society of Anesthesiologists (ASA), 2 Amicar, 983 Amide local anesthetics, 970–971 Amiloride, 1010 Aminoglycosides, 977 Amiodarone, 619, 975 in atrial fibrillation, 100 in atrial flutter, 103 in hypertrophic cardiomyopathy, 461 in ventricular tachycardia and ventricular fibrillation, 13 Amitriptyline, 987t Amlodipine, 1002t Amniotic fluid embolism (AFE), 40–41 physiologic alterations in, 40 serum markers for, 41 treatment of, 41 Amphetamines, 828 Ampicillin/Sulbactam, 978 Amsorb, 158. See also Carbon dioxide absorbers Amyloidosis, 42–43 Amyotrophic lateral sclerosis (ALS), 44–45 Anacrotic limb, 86 Anaerobic metabolism, 46–47 Analgesics, in multiple myeloma, 576 Anaphylaxis, 48–49 Ancef. See Cefazolin Anemia, 50–51, 424, 445 Anemia of prematurity (AOP), 52–53 Anesthesia care providers, addiction in, 858–859 Anesthesia for neuroradiology, 54–55 challenges in, 54 indications for, 54 Anesthetic agents, and cadiac arrest, 12

Anesthetic goals/guiding principles. See specific topics Anesthetized extubation. See Deep extubation Angina and chest pain, 686 chronic, 226–227 stable, 226 Angiotensin, 56–57 Angiotensin-converting enzyme inhibitors (ACEIs), 10, 972, 972t blood flow resistance and, 127 and hypotension, 10–11 Angiotensin I, 56 Angiotensin II, 34, 56, 127 Angiotensin receptor antagonists, in diabetes mellitus, 328 Angiotensin receptor blockers (ARBs), 10, 57, 973, 973t in angina, 226 blood flow resistance and, 127 in Raynaud’s phenomenon, 762 Anion gap (AG), 58–59, 556 equation, 151 metabolic acidosis, 46 Antacids, 223, 439 in gastroesophageal reflux disease, 408, 409 Anterior cervical discectomy and fusion (ACDF), 60–61 Anterior ischemic optic neuropathy, 642 Anterior mediastinal mass, 62–63 Anterograde cerebral perfusion, 236 Anthracyclines (doxorubicin, daunorubicin, idarubicin, epirubicin), 1005 Antianginal therapy, 226 Antiarrhythmics, 165, 974–975 class IA, 974, 974t class IB, 974–975 class IC, 975, 975t Antibiotics, 976–979. See also specific drugs in chronic bronchitis, 228 in septic shock, 807 Anticholinergics, 980–981 in aortic regurgitation, 75 in multiple sclerosis, 578 in Parkinson’s disease, 628 in postoperative nausea and vomiting, 697 Anticholinesterases, effect on autonomic nervous system, 113 Anticoagulants and reversals, 982–983 Anticonvulsants, 984–985 in cerebral palsy, 210

in complex regional pain syndrome, 253 in CRPS Type II, 255 Antidepressants, 986–989 in amyotrophic lateral sclerosis, 44 in multiple sclerosis, 578 Antidiuretic hormone (ADH), 64–65, 668 Antidopaminergics, in hiccups, 440 Antidote treatment, in cyanide poisoning, 307 Antiemetics, 990–993. See also specific drugs and tardive dyskinesia, 852 Antiepileptic drugs (AEDs) in alcohol withdrawal syndrome, 31 in hiccups, 441 and seizures, 804 Antifibrinolytics, 66–67 clinical uses, 66 side effects of, 66 Antihistamines, 994–995 Antihyperglycemics, in lower extremity amputation, 536 Antihypertensives in autonomic hyperreflexia, 111 in hyperaldosteronism, 35 in lower extremity amputation, 536 in preeclampsia, 710 in thoracic aortic aneurysm repair, 860 Antiplatelet agents in chronic angina, 227 in lower extremity amputation, 536 Antipsychotics in alcohol withdrawal syndrome, 31 in postoperative delirium, 691 Antispasmodic agents, 996–997 Antithrombin. See Antithrombin III (ATIII) Antithrombin III (ATIII), 68–69 concentrates, 68 Antoven. See Warfarin Anzemet. See Dolasetron Aortic bodies, 624 Aortic dissection, 70–71 and chest pain, 686, 687 Aortic pressure curve, 72–73 Aortic regurgitation (AR), 74–75, 720 acute, 74 chronic, 74

Aortic stenosis (AS), 76–77, 720 Aortic valve, 74, 76 Aortic valve replacement, 78–79 Aortocaval compression, 80–81 Apnea of prematurity (AOP), 82–83 Apnea test, 142 Appendectomy, 84–85 laparoscopic, 84 open, 84 Appendicitis, 84 Aprepitant, 991 in postoperative nausea and vomiting, 697 Apresoline. See Hydralazine Aprotinin, 67, 982 ARDS. See Acute respiratory distress syndrome (ARDS) Arformoterol, 999t Aripiprazole, 1007t Arrhythmias from abnormal repolarization, 165 electrocardiography and, 2 statin therapy and, 648 Arterial blood pressure, control systems for, 56 Arterial line waveform, 86–87 Arterial PO2, 36

Arterial transducers, 87 Arteries, 126 Arteriovenous malformation (AVM), 235 brain, 202–203 Spetzler–Martin grading scale for, 203 Articadent. See Articaine Articaine, 970 Ascites, 238, 533 Aspartate transaminase, 526 Aspiration, 88–89 consequences of, 88 pneumonia , 88, 686, 687 pneumonitis, 88 in pregnant patients, 88 prevention of, 88–89 treatment of, 89 Aspiration pneumonitis of acidic solutions, 39 Aspirin, 1034t in chronic angina, 227 in peripheral vascular disease, 652

in preeclampsia, 708 Assist control ventilation (A/C), 92–93 Assisted mechanical ventilation (AMV). See Assist control ventilation (A/C) Asthma, 94–95 Asthma/COPD drugs, 998–999 Atacand. See Candesartan Atarax. See Hydroxyzine Atelectasis, 36, 38, 96–97 absorption, 96 from anesthesia, 96 compression, 96 and development of IPS, 808 loss-of-surfactant, 96 treatment of, 97 Atenolol, 1000t Atherosclerosis, statin therapy and, 648 Atorvastatin, 1020t Atosiban, in preterm labor, 724 ATP (adenosine triphosphate), 46 Atracurium, 442, 959, 1033 Atria, 98–99 Atrial bradycardia, 99 Atrial fibrillation (AF), 99, 100–101, 650 Atrial flutter (AFL), 99, 102–103. See also Tachycardia and atrial fibrillation, 102 (See also Atrial fibrillation (AF)) atypical, 102 typical, 102 Atrial kick, 332 Atrial natriuretic peptide (ANP), 98, 300 Atrial septal defect (ASD), 98, 104–105 clinical sequelae of, 104 ostium primum, 104 ostium secundum, 104 sinus venosus, 104 Atrial tachycardia (AT), 99, 106–107 Atrioventricular (AV) node, 98, 174 Atropine, 980. See also ACLS anesthetic management; Bradycardia in amyotrophic lateral sclerosis, 44 in apnea of prematurity, 83 in bradycardia, 141, 169 in breastfeeding mothers, 511 in hiccups, 440 in postoperative nausea and vomiting, 697 Atrovent. See ipratropium

ATryn. See Recombinant human concentrate Atypical antipsychotic agents, 1007, 1007t Autoimmune thrombocytopenia, 862. See also Thrombocytopenia Autologous blood transfusion, 108–109 Automated external defibrillators (AEDs), 319 Autonomic dysreflexia (AD). See Autonomic hyperreflexia (AH) Autonomic hyperreflexia (AH), 110–111, 131 Autonomic nervous system (ANS), 112–113 Avapro. See Irbesartan AV blocks, 2 and bradycardia, 140–141 AV conduction disturbances, 175 AVP (8-arginine vasopressin), 64 Awake craniotomy, 114–115 asleep-awake-asleep techniques, 114–115 Awareness during anesthesia, 116–117 Axid. See Nizatidine Axis deviation, 2 Azactam. See Aztreonam Azathioprine, in multiple sclerosis, 578 Azilect. See Rasagiline Aztreonam, 977 B Bacillus anthracis, 480 Baclofen, 996 in amyotrophic lateral sclerosis, 44 in cerebral palsy, 210 in hiccups, 440 in multiple sclerosis, 578 Bactrim. See Trimethoprim/sulfamethoxazole (TMP/SMX) Bactroban. See Mupirocin Baralyme, 158. See also Carbon dioxide absorbers Barbiturates and burst suppression, 156 and cerebral metabolic rate, 208 and EEG, 357 Bare metal stents (BMS), 166, 282. See also Coronary stent Bariatric surgery, 118–119 malabsorptive procedures, 118 restrictive procedures, 118 Roux-en-Y gastric bypass (RYGB), 118 Barotraumas, 501 Bases, 150. See also Buffering systems

Beach chair position, laryngoscopy, 516, 517f Behavioral pain scale (BPS), 91 Benadryl. See Diphenhydramine Benazepril, 972t Benicar. See Olmesartan Benzocaine, 1017 Benzodiazepines in alcohol withdrawal syndrome, 29, 31 in aortic stenosis, 77 in burn, 153 and cerebral metabolic rate, 209 in cyanide poisoning, 307 effect on autonomic nervous system, 112 in gastrectomy, 407 in hepatic encephalopathy, 433 and MEPs, 819 in perioperative seizures, 647 Beta-adrenergic blockers, See Beta-blockers Beta-blockers, 1000–1001, 1000t, See also specific types in abdominal aortic aneurysms, 4 in angina, 226 in aortic dissection, 71 in atrial flutter, 103 in atrial tachycardia, 106 and AV conduction disturbances, 175 blood flow resistance and, 127 and cerebral metabolic rate, 209 in hyperthyroidism, 458 in hypertrophic cardiomyopathy, 461 in lower extremity amputation, 536 in neurogenic pulmonary edema, 597 in peripheral vascular disease, 652in preterm labor, 724 in thoracic aortic aneurysm repair, 860 Betamethasone, in HELLP syndrome, 423 Betapace. See Sotalol Beta-receptors, in SA node, 230 Bicarbonate, as epidural, 370 Bier block, 120–121 benefits of, 120 contraindications to, 120 limitations of, 120 technique, 120–121 Biliary atresia (BA), 506. See also Kasai procedure Bilirubin, 526

Biofeedback technology, in complex regional pain syndrome, 253 Bioimpedance cardiography, 171 Bioterrorism agents, infection from, 480 Bispectral index (BIS), 117, 356 Bisphosphonates, in CRPS Type II, 255 Biventricular–ventricular assist devices (BIVAD), 550 Bladder, 704 Blalock–Taussig (BT) shunt, 122–123 classic, 122 modified, 122 Bleeding, post-tonsillar, 682–683 Blenoxane. See Bleomycin Bleomycin, 619, 1004 Blood brain barrier (BBB), 341 Blood coagulation physiology, in pregnancy, 124–125 Blood flow resistance (BFR), 126–127 Blood gas analyzers, 654 Blood oxygen-carrying capacity, 128–129 Blood pressure (BP), 130–131 diastolic, 130 mean, 130 measurement of, 130 regulation of, 10, 130 systolic, 130 Blood sludging, 28 Blood substitutes, 132–133 Blood transfusion, 129 Bochdalek hernia, 257 Bohr effect, 150 Bohr equation, 314, 315, 929 Bone, and acid–base buffering system, 151 Bone graft migration, 61 Bone marrow transplants (BMT), 134–135 Bortezomib in amyloidosis, 42 in multiple myeloma, 576 Botulinum, in cerebral palsy, 210 Botulism, 481 Bowel/colon resections, 136–137 Boyle’s gas law, 444 Brachial plexus anatomy, 138–139, 139f Brachial plexus injury, 138 Bradycardia, 140–141 Bradykinin, 162

Brain arteriovenous malformations (BAVM), 202–203 Brain death, 142–143 Brain natriuretic peptide (BNP), 98, 300 Breathing circuit, 144–145, 145f advantages of, 144 closed, 144 components of, 144 integrity of, checking of, 145 open, 144 semi-closed, 144 semi-open, 144 Breathing efficiency, 314 Brethine. See Terbutaline Brevibloc. See Esmolol Bromocriptine, in Cushing’s syndrome, 305 Bronchial circulation, 38 Bronchiectasis, 146–147 Bronchodilators in chronic bronchitis, 228 in cystic fibrosis, 309 Bronchoscopy flexible, 148–149 rigid, 148–149 Brovana. See Arformoterol Brugada syndrome, 165 Buffering systems, 150–151 Bundle branch blocks, electrocardiography and, 2 Bupivacaine, 970 Buprenorphine, 1038 Bupropion, 988 Burns, 152–153 Burr hole, 154–155 Burst suppression (BS), 156–157 Butyrophenone. See Droperidol Byetta. See Exenatide C CABG. See Coronary artery bypass grafting (CABG) Caffeine in apnea of prematurity, 82, 83 in post-dural puncture headache, 684 Calcium channel blockers (CCBs), 1002–1003 in angina, 226 in atrial tachycardia, 107

and AV conduction disturbances, 175 blood flow resistance and, 127 in cerebral vasospasm, 212 dihydropyridine, 1002, 1002t in hypertrophic cardiomyopathy, 461 and myocardial contractility, 25 non-dihydropyridine, 1003, 1003t in preterm labor, 724 in pulmonary hypertension, 744 in Raynaud’s phenomenon, 762 Calcium (chloride and gluconate), 1015 Caldolor, 1034t Candesartan, 973t Capoten. See Captopril Capsaicin, 987 Captopril, 972t Carafate. See Sucralfate Carbamazepine, 985 in alcohol withdrawal syndrome, 31 in amyotrophic lateral sclerosis, 44 in multiple sclerosis, 578 Carbaminohemoglobin, 160 Carbatrol. See Carbamazepine Carbocaine. See Mepivacaine Carbon dioxide absorbers, 158–159 Carbon dioxide transport, in blood, 160–161 Carbon monoxide (CO) generation of, 158 poisoning, 444 Carboprost tromethamine, 1025 Carboxyhemoglobinemia, 425 Carcinoid syndrome, 162–163 Carcinoid tumors, 162–163 Cardene. See Nicardipine Cardiac action potential, 164–165 Cardiac arrest, 318 in OR, 12–13 anesthetic causes of, 13 Cardiac catheterization, 166–167 left, 166 right, 166 Cardiac contractility, 586 Cardiac glycosides, and AV blocks, 175 Cardiac hypertrophy, angiotensin and, 57

Cardiac implantable electronic device (CIED), 620 Cardiac index (CI), 168 Cardiac output (CO), 168–169 high, 172–173 measurement of, 170–171 Cardiac pacemaker cells, 164, 174–175, 175f Cardiac protection, statin therapy and, 648 Cardiac surgery with CPB antifibrinolytics in, 66 and strokes, 650 transcranial Doppler use in, 883 Cardiogenic pulmonary edema (CPE), 176–177 Cardioplegia, 178–179 anterograde, 179 blood, 178 cold, 178 crystalloid, 178 retrograde, 179 warm, 178 Cardiopulmonary bypass (CPB), 180–181 adult vs. pediatric, 181 cardioplegia during, 178–179 hyperlactatemia and, 47 and splanchnic blood flow, 411 Cardizem. See Diltiazem Carisoprodol, 996–997 Carmustine, in amyloidosis, 42 Carotid artery disease, statin therapy and, 648 Carotid body (CB), 182–183, 624 Carotid endarterectomy (CEA), 184–185, 650 cervical plexus blockade for, 217 transcranial Doppler use in, 883 Carotid sinus, 186–187, 186f Carotid sinus syndrome (CSS), 186 Carotid stenosis, cerebral blood flow in, 205 Carvedilol, 1000t in hiccups, 441 Cataflam. See Diclofenac Catapres. See Clonidine Cataract surgery, 188–189 Catecholamine infusion, in bradycardia, 141 Caudal epidurals, 190–191 CEA. See Carotid endarterectomy (CEA)

Cefazolin, 978 in adrenalectomy, 23 Cefotetan, 978 Cefoxitin, 978 Celebrex. See Celecoxib Celecoxib, 1035 Celexa. See Citalopram Celiac plexus block (CPB), 192–193 Cell membrane, 194–195, 194f Cell salvage, 196–197 Cell saver. See Cell salvage Cement implantation syndrome (CIS), 198–199 Central lines, 200–201 Central nervous system angiotensin II effect on, 56 energy consumption of, 46 and medications, , 1006–1007 Central retinal artery occlusion, 642 Central venous catheter (CVC), 200. See also Central lines Cephalosporins, 978 Cerebral aneurysms, 234 Cerebral arteriovenous malformation, 202–203 Cerebral blood flow (CBF), 204–205 and cerebral metabolic rate of oxygen, 208 Cerebral embolization, 206–207 Cerebral injury, 237 Cerebral metabolic oxygen consumption. See Cerebral metabolic rate (CMR) Cerebral metabolic rate (CMR) , 208–209, 502 Cerebral palsy (CP), 210–211 Cerebral perfusion pressure (CPP), 490 Cerebral vasospasm, 205, 212–213 Cerebrospinal fluid (CSF), 214–215 Cerebrovascular accident (CVA), 234 Cervical plexus block, 216–217 Cervical ultrasonography, 725 Cessation of systemic circulation, 236–237 CHADS2 score, 100 Chemotherapeutic agents, 1004–1005 Chest pain, postoperative, 686–687 Chest tubes, 218–219 Chest x-ray (CXR), 220–221 Child-Pugh score, 433, 527 Children’s Revised Impact of Event Scale (CRIES), 91 Child–Turcotte–Pugh (CTP) scores, 360

Chloride ions, 222–223 Chloroprocaine, 1016 Chlorpromazine in hiccups, 440 in neurogenic pulmonary edema, 597 in postoperative shivering, 703 Cholecystectomy, 224–225 laparoscopic, 224 open, 224 Cholinergic crisis, 580 Chronic angina, 226–227 Chronic bronchitis, 228–229 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), for GFR estimation, 419 Chronic obstructive pulmonary disease (COPD), 228 chest x-ray in, 220 Chronotropy, 230–231 negative, 230 positive, 230 Cilia, 232 Ciliary function, 232–233 Cilostazol, in peripheral vascular disease, 652 Cimetidine, 1019 in anaphylaxis, 49 Cimetidine administration, 292 Cinchocaine. See Dibucaine Ciprofloxacin (Cipro), 977 Circle of Willis (coW), 234–235 Circulatory arrest, 236–237 Cirrhosis, 238–239 Cirrhotic cardiomyopathy, 172 Cisatracurium, 442, 959, 1033 Citalopram, 986t Citanest. See Prilocaine Citric acid cycle, 46 Cleft palate/cleft lip, 240 repair, 240–241 Cleocin. See Clindamycin phosphate Clevidipine, 1002t Cleviprex. See Clevidipine Clindamycin, in adrenalectomy, 23 Clindamycin phosphate, 976 The Clinical Institute for Withdrawal Assessment (CIWA), 31 Clinical pulmonary infection score (CPIS), 938 Clonazepam, 985

Clonidine, 1031 in alcohol withdrawal syndrome, 31 as epidural, 370 in postoperative shivering, 703 Clopidogrel, 1050t in chronic angina, 227 Closing capacity, 242–243, 242f, 243f Closing volume (CV), 242 Clostridial myositis, 444 CNS acting drugs, 1006–1007 Cocaine, 1008–1009 Cocaine abuse, 244–245, 828 Cockcroft–Gault formula, for GFR estimation, 419 Codeine, 1036 in breastfeeding mothers, 511 Cognitive-behavioral therapy (CBT), in complex regional pain syndrome, 253 Colloids, 246–247, 1010–1011 natural, 246 semisynthetic, 246 Colonoscopy, 248–249 Combined spinal-epidural analgesia (CSE), 250–251 Combitube, 836 Combivent. See Albuterol/ipratropium Compazine. See Prochlorperazine Complex regional pain syndrome (CPRS) Type I, 252–253 Type II, 254–255 Compliance, 776. See also Respiratory system compliance COMT inhibitors, in Parkinson’s disease, 628 Conduction abnormalities, 99 Congenital diaphragmatic hernia (CDH), 256–257 Congestive heart failure (CHF), 39, 258–259 and development of IPS, 808 Conn syndrome, 34. See also Aldosterone Context-sensitive half-time, 260–261 Continuous positive airway pressure (CPAP), 262–263 Contractility, 848 Contrast dye reactions, 55 Contrast nephropathy, 55 Controlled hypotension, 264–265 Cooling of heart, 266–267 Cordarone. See Amiodarone Coreg. See Carvedilol Corlopam. See Fenoldopam

Corneal abrasions, 270–271 Coronary angiography, 166 Coronary arteries, 272–273, 272f Coronary artery bypass grafting (CABG), 166 off-pump, 276–277 on pump, 274–275 Coronary artery disease (CAD), 273, 278–279 angiotensin and, 56 Coronary artery dominance, 272 Coronary artery spasm (CAS), 226, 280–281 Coronary blood flow (CBF), 272 Coronary collaterals, 273 Coronary perfusion pressure, 130 Coronary sinus ASD, 98 Coronary stent, 282–283 Coronary–subclavian steal syndrome, 826 Cor pulmonale, 228, 268–269 Corticosteroids in ARDS, 21 in atrial fibrillation, 101 in chronic bronchitis, 228 in complex regional pain syndrome, 253 in CRPS Type II, 255 in IgA deficiency, 479 in placenta previa, 664 in rheumatoid arthritis, 788 Cortisol, 284–285, 304 deficient states, 284 excess states, 284 Cortisol-producing adenomas, adrenalectomy for, 22–23 Costochondritis, and chest pain, 686 Cosyntropin in post-dural puncture headache, 684 in trauma, 898 Co-trimoxazole. See Trimethoprim/ sulfamethoxazole (TMP/SMX) Coughing, 88 Coumadin. See also Warfarin in ATIII deficiency, 68 Cozaar. See Losartan CPB. See Cardiopulmonary bypass (CPB) CPR, in cardiac arrest, 13 Craniosynostosis, 286–287 Craniotomy awake (See Awake craniotomy)

for cerebral aneurysm clipping, 288–289 for intracranial hemorrhage, 290–291 Creatinine, 292 Creatinine clearance (CrCl), 292–293 Crestor. See Rosuvastatin Creutzfeldt–Jakob disease, 480, 481 Cricothyroid membrane, 294, 295f Cricothyroidotomy, 294–295, 295f needle (cannula) technique, 294, 295f Seldinger technique, 294, 295f surgical technique, 294, 295f Critical Care Pain Observation Tool (CPOT), 91 Critical red cell mass, 18 Crohn’s disease, 296–297 Crush injury, 444 Cryoprecipitate, 298–299 Crystalloids, 246, 300–301 CSF, leakage of, 214 CU-2010, 67 Cuff-leak test, 499 Cushing’s disease, 284, 304 Cushing’s reflex, 302–303 Cushing’s syndrome, 284, 304–305 Cutaneous innervations, to head and neck, 216 Cyanide antidote kit (CAK), 307 Cyanide poisoning, 306–307 Cyanosis, 637 Cyclizine, in postoperative nausea and vomiting, 697 Cyclobenzaprine, 997 Cyclophosphamide, 1004 in amyloidosis, 42 in multiple sclerosis, 578 Cymbalta. See Duloxetine Cystatin C, 700 Cystic fibrosis (CF), 39, 223, 308–309 Cystoscopy, 310–311 Cytoxan. See Cyclophosphamide D Dabigatran, in atrial fibrillation, 100 Dalteparin-Fragmin. See Low molecular weight heparin (LMWH) Dalton’s law of partial pressure, 387 D2 antagonists, in postoperative nausea and vomiting, 697

Dantrium. See Dantrolene

Dantrolene, 997 DDAVP. See Desmopressin (DDAVP) D-dimer, 312–313 Dead space (VD), 312, 314–315, 748, 866 Decadron. See Dexamethasone Decompression sickness, 444 Deep extubation, 316–317 Deep hypothermic circulatory arrest (DHCA), 181 Deep venous thrombosis (DVT), 312, 738 in pregnancy, 124 treatment of, 1054–1055 Deferoxamine, 856 Defibrillation, 318–319 Degenerative disc, 60 and epidural steroid injection, 377 Delayed radiation injury, 445 Deliberate hypotension. See Controlled hypotension Delirium, 688 postoperative, 690–691 Delirium tremens (DT), 30. See also Alcohol withdrawal syndrome (AWS) Delta waves, 2 Dementia, 320–321, 688 Denervated heart, 680 Dental damage, 322–323 4ʹ-iodo-4ʹ-deoxydoxorubicin, in amyloidosis, 42 Depakene. See Valproic acid Depolarizing muscle relaxants, and cerebral metabolic rate, 209 Deprenyl, in Parkinson’s disease, 628 Depression, 324–325 Desflurane, 1052 Desipramine, 987t Desmopressin (DDAVP), 65, 1022 in diabetes insipidus, 326, 327 in hemophilia, 428 in thrombocytopenia, 863 Detoxification, in body, 306 Dexamethasone, 991 in amyloidosis, 42 in awake craniotomy, 114 in multiple myeloma, 576 in postoperative nausea and vomiting, 697 Dexlansoprazole, 1045 Dexmedetomidine, 107, 1027 in alcohol withdrawal syndrome, 31

in awake craniotomy, 114 in bronchoscopy, 149 in burn, 153 context-sensitive half-time, 260 as epidural, 370 in postoperative delirium, 693 in postoperative shivering, 703 Dextran 40, 1011 Dextran 70, 1011 Dextrans, 246, 1011. See also Colloids Dextromethorphan, in amyotrophic lateral sclerosis, 44 Dextrose 5% in water, 300, 301 DiaBeta. See Glyburide Diabetes insipidus (DI), 64, 326–327, 668 Diabetes mellitus (DM), 328–329 type I, 328 type II, 328 Diabetic ketoacidosis (DKA), 330–331 Diastole, 332–333 Diastolic dysfunction, 720 Diastolic heart failure (DHF), 332 Diazepam, 961, 1029 in breastfeeding mothers, 510 in eclampsia, 348 in HELLP syndrome, 423 Dibucaine number (DN), 334–335 Diclofenac, 1034t Dicrotic limb, 86 Dicrotic notch, 86 Difficult airway, 336–337 Difficult peripheral intravenous access, 338–339 Diffusion, 340–341 Diffusion capacity, 624 Diffusion defects, 36 Digoxin, 974 in atrial flutter, 103 in atrial tachycardia, 107 toxicity and EKG changes, 3 Dihydropyridines, 1002, 1002t Dilantin. See Phenytoin Dilated cardiomyopathy, 165 Diltiazem, 1103t in atrial flutter, 103

in intraoperative hypertension, 131 Dilutional thrombocytopenia, 862. See also Thrombocytopenia Diovan. See Valsartan Dipeptidyl dipeptidase inhibitors, 328, 1041 Diphenhydramine, 994 in anaphylaxis, 49 in IgA deficiency, 479 in postoperative nausea and vomiting, 697 Disease modifying anti-rheumatic drugs (DMARDs), in rheumatoid arthritis, 788 Disopyramide, 974t in atrial flutter, 103 Disseminated intravascular coagulopathy (DIC), 862. See also Thrombocytopenia D-dimer assays and, 313 Diuretics, 1010–1011 in cardiogenic pulmonary edema, 177 in pulmonary hypertension, 744 Dobutamine, 1043 in cardiogenic pulmonary edema, 177 and cerebral metabolic rate, 209 in intraoperative hypotension, 131 in neurogenic pulmonary edema, 597 Dobutrex. See Dobutamine Docetaxel. See Taxanes Dofetilide, in atrial flutter, 103 Dolasetron, 990 in postoperative nausea and vomiting, 697 Dopamine, 1043 blood flow resistance and, 127 in bradycardia, 141 in cardiogenic pulmonary edema, 177 effect of alcohol on, 28 for intraoperative hypotension, 131 Dopamine agonists, in Parkinson’s disease, 628 Doppler ultrasound (esophageal Doppler probe), 170, 173 Double lumen endotracheal tubes (DLT), 342–343 Doxacurium, 1033 Doxapram, in postoperative shivering, 703 Doxazosin, 1031t in pheochromocytoma, 656 Doxorubicin, in multiple myeloma, 576 Doxycycline, 979 Drinker’s nose, 28 Dronabinol, 546 Droperidol, 992

in hiccups, 440 in postoperative nausea and vomiting, 697 and tardive dyskinesia, 852 Drug-eluting stents (DES), 166, 282. See also Coronary stent Duchenne’s muscular dystrophy (DMD), 344–345 Duloxetine, 986t Duranest. See Etidocaine Dyes, 1012–1013 Dyrenium. See Triamterene Dysfibrinogenemia, 398 Dyshemoglobins, 129 Dysphagia, 346–347 E Early myoclonic encephalopathy (EME), 156 Echocardiography atrial flutter, 103 for ejection fraction measurement, 350 Eclampsia, 348–349 ECMO, in propofol infusion syndrome, 727 Edrophonium, 1048 Effexor. See Venlafaxine Effient. See Prasugrel Eicosapentaenoic acid (EPA), in ARDS, 21 Ejection fraction (EF), 168, 350–351 EKG, 12-lead, 2–3, 273 Elastance, 776 Elavil. See Amitriptyline Electrical safety, in operating room, 352–353 Electroconvulsive therapy (ECT), 354–355 Electroencephalogram (EEG), 356–357 burst suppression pattern on, 156–157 Electrolyte abnormalities, and EKG changes, 3 Electrolytes, 1014–1015 Electromyography (EMG), 358–359 Electron transport chain (ETC), 306 Emend. See Aprepitant Emergency pacing, in cadiac arrest, 13 EMLA. See Lidocaine; Prilocaine Emphysema, 39 Enalapril, 972t Enalaprilat, in aortic dissection, 71 Endoscopic retrograde cholangiography (ERCP), 364–365 Endoscopic sinus surgery, 366–367

Endothelial receptor antagonist, in pulmonary hypertension, 744 Endovascular aortic repair (EVAR), 368–369 and open repair, 368 End-stage liver disease (ESLD), 172, 360–361. See also Kidney transplantation End systolic volume (ESV), 168 End tidal carbon dioxide (ETCO2), 362–363

Enoxaparin-Lovenox. See Low molecular weight heparin (LMWH) Entacapone, in Parkinson’s disease, 628 Enteric nervous system, 112 Enzyme-linked immunosorbent essay (ELISA), 431 Ephedrine, 1042 in bradycardia, 141 and EEG, 357 in hiccups, 440 in hypotension, 11 for intraoperative hypotension, 131 Epidural, 370–371 Epidural abscess, 370, 372–373 Epidural blood patch, in post-dural puncture headache, 684, 685 Epidural dextran, in post-dural puncture headache, 685 Epidural hematomas, 370, 374–375 Epidural space, 374 Epidural steroid injection (ESI), 376–377 caudal, 376 interlaminar, 376 transforaminal, 376 Epiglottitis, 378–379 Epinephrine, 1042 in anaphylaxis, 49 in asthma, 95 blood flow resistance and, 127 in bradycardia, 141 and cerebral metabolic rate, 209 and EEG, 357 as epidural, 370 in intraoperative hypotension, 131 Eplerenone, 1010 Eprosartan, 973t Epsilon-aminocaproic acid (EACA), 66. See also Antifibrinolytics Ertapenem, 977–978 Erythropoietin, in multiple myeloma, 576 Escitalopram, 986t ESLD. See End-stage liver disease (ESLD) Esmolol, 1000t

in abdominal aortic aneurysms, 5 in intraoperative hypertension, 131 Esomeprazole Magnesium and Esomeprazole Sodium (IV) (Nexium®), 1044 Esophageal intubation, 380–381 Esophageal pacing (EP), 621 Esophageal spasm, and chest pain, 686 Esteratic local anesthetics, 1016–1017 Etidocaine, 970–971 Etomidate, 959, 1028 and cerebral metabolic rate, 208 effect on autonomic nervous system, 112 and MEPs, 819 European System for Cardiac Operative Risk Evaluation, 78 Exenatide, 1041 Expiration, 88 Expiratory reserve volume (ERV), 772 Expiratory time, 476 Extracapsular cataract extraction (ECCE), 188 Extracellular fluid, 382–383 Extracorporeal shockwave lithotripsy (ESWL), 384–385 F Faces Legs Activity Cry Consolability Scale (FLACC), 91 Faces Pain Scale-Revised (FPS-R), 91 Facet joint injections, lumbar, 388–389 Factor I deficiency, 398 Factor VII, 486, 632. See also International normalized ratio (INR); Prothrombin time (PT); Recombinant activated factor VII (rFVIIa) Familial antithrombin deficiency, 68 Famotidine, 1018 in gastroesophageal reflux disease, 409 Fat embolus syndrome, 390–391 Felodipine, 1002t Felty syndrome, 789 Femoral artery, 86 Femoral nerve block, 392–393 Fenoldopam, 1030–1031 Fentanyl, 959, 1037 in breastfeeding mothers, 511 context-sensitive half-time, 260 in hepatic encephalopathy, 433 Fetal cardiovascular physiology, 394–395 Fetal fibronectin (FFN), 725 Fetal heart tones, 396–397, 397f

umbilical cord prolapse and, 912, 913 uterine rupture and, 926 Fetal hemoglobin (HbF), 52, 128, 160, 783, 856. See also Thalassemia FFP. See Fresh frozen plasma (FFP) Fiberoptic bronchoscopy (FOB), 337 Fibrinogen, 398–399 Fibrinogen replacement therapy, 299 Fick’s method, for CO measurement, 170 Fingolimod, in multiple sclerosis, 578 F-inspiratory (FI), 386–387

Fire, operating room, 614–615 Flagyl. See Metronidazole Flecainide, 975, 975t in atrial flutter, 103 Flexeril. See Cyclobenzaprine Flow volume loops, 400–401 fixed extrathoracic obstruction, 401f functional effects of mass by, 401, 401f lung flows, 400f normal, 400f obstructive lung disease, 400f restrictive lung disease, 400f spirometry and lung volumes, 400f variable extrathoracic obstruction, 401f variable intrathoracic obstruction, 401f vocal cord dysfunction, 401f Fludrocortisone, in hypoaldosteronism, 35 Fluid collections, in pleural space, 219 Fluid creep, in burn resuscitation, 153 Fluid deficit calculations, 301 Fluid resuscitation, in burn, 153 Flumazenil, 1029 and cerebral metabolic rate, 209 in hepatic encephalopathy, 432 Fluoroquinolones, 977 5-fluorouracil, 1004 Fluoxetine, 986t in Raynaud’s phenomenon, 762 Fluvastatin, 1020t Focal atrial tachycardia (FAT), 106. See also Atrial tachycardia (AT); Synchronized electrical cardioversion Foradil. See Formoterol Foreign body, and chest x-ray, 221 Formoterol, 999, 999t

Fosinopril, 972t Fosphenytoin, 985 Fossa ovalis, 98 Fowler’s method, for dead space measurement, 314 Fractional excretion of sodium (FENa), 705. See also Postrenal acute kidney injury; Prerenal acute kidney injury Fractional oximetry, 625 Frank–Starling law, 168. See also Cardiac output; Preload Free water deficit calculations, 301 Freezing point depression osmometry, 668 Fresh frozen plasma (FFP), 402–403 transfusion, in ATIII deficiency, 68 Functional endoscopic sinus surgery (FESS). See Endoscopic sinus surgery Functional oximetry, 625 Functional pacing dependency, 620–621 Functional pain scales, 91 Functional residual capacity (FRC), 242–243, 404–405, 772 Furosemide, 1010 and ICP, 491 G GABA-B agonists in complex regional pain syndrome, 253 in CRPS Type II, 255 GABA (gamma-aminobutyric acid) receptors, 222 effect of alcohol on, 28 Gabapentin, 984 in complex regional pain syndrome, 253 in hiccups, 440 in post-dural puncture headache, 685 Gamma-linoleic acid (GLA), in ARDS, 21 Garamycin. See Gentamicin Gastrectomy, 406–407 Gastroesophageal reflux disease (GERD), 211, 309, 408–409, 438, 440. See also Antacids; H2 blockers; Hiatal hernia and chest pain, 686 Gastrointestinal blood flow, 410–411 Gastroschisis, 412–413 Gelatins, 246. See also Colloids Gentamicin, 977 Geodon. See Ziprasidone GERD. See Gastroesophageal reflux disease (GERD) Geriatric physiology, 414–415 Gestational diabetes mellitus (GDM), 416–417

Gestational thrombocytopenia, 124 Gigantism, 14 Glatiramer acetate, in multiple sclerosis, 578 Glimepiride, 1040t Glipizide, 1040t Global Initiative for Chronic Obstructive Lung Disease (GOLD), 228 Glomerular filtration rate (GFR), 418–419, 704 Glucagon, 1022 Glucocorticoids, 16 in hyperthyroidism, 458 in hypoaldosteronism, 35 in multiple sclerosis, 579 Gluconeogenesis, 46, 330 Glucophage. See Metformin Glucotrol. See Glipizide Glutamate, effect of alcohol on, 28 Glyburide, 1040t Glycine receptor, effect of alcohol on, 28 Glycogenolysis, 46 Glycolysis, 46 Glycopyrrolate, 980 in bradycardia, 141 Glycopyrronium, in amyotrophic lateral sclerosis, 44 Glycosuria, 330 Granisetron, 990 in postoperative nausea and vomiting, 697 in postoperative shivering, 703 Graves’ disease, 458 Growth hormone (GH), overproduction of, 14. See also Acromegaly Growth hormone-releasing hormone (GHRH), 14 H Hagen–Poiseuille equation, 512 Haldol. See Haloperidol Haloperidol, 992 in alcohol withdrawal syndrome, 31 in hiccups, 440 in postoperative delirium, 691 in postoperative nausea and vomiting, 697 and tardive dyskinesia, 852 Halothane, 1053 H2 antagonists. See H2 blockers Hardware fracture, 61 Hashimoto’s thyroiditis, 458

H2 blockers, 223 in hiccups, 440 and non-particulate antacids, 1018–1019 Health-care workers, infection risk in, 480–481 Heart failure (HF). See also Congestive heart failure (CHF) carotid body and, 183 and chest x-ray, 221 Heart transplant, 420–421 Heliox, 95, 378, 512, 1047, See also Laminar airflow in asthma, 95 HELLP syndrome, 422–423, 862 Hemabate. See Carboprost tromethamine Hemodynamics, during dilutional anemia, 18 Hemoglobin, 128, 424–425, 624. See also Blood oxygen-carrying capacity; Thalassemia Hemoglobin-based oxygen carriers (HBOCs), 132. See also Blood substitutes First-generation, 132 Second-generation, 132 Third-generation, 132 Hemolysis, Elevated Liver enzymes, Low Platelet counts (HELLP) Syndrome in pregnancy, 124 Hemolytic anemia, 426–427 acquired, 426 inherited, 426 Hemolytic disease of the newborn (HDN), 786 Hemolytic uremic syndrome (HUS), 124, 862. See also Thrombocytopenia Hemophilia, 428–429 Hemopure, 132 Henderson-Hasselbach equation, 151 Henry’s law, 386, 444 Heparin, 430, 982 in ATIII deficiency, 68 in peripheral vascular disease, 652 in pulmonary embolism, 739 Heparin cofactor 1. See Antithrombin III (ATIII) Heparin-induced platelet aggregation (HIPA), 431 Heparin-induced thrombocytopenia (HIT), 86, 430–431, 862. See also Thrombocytopenia type I, 430 type II, 430 Hepatic arterial buffer response (HABR), 410, 532 Hepatic artery, 532 Hepatic encephalopathy (HE), 238, 432–433 Hepatic veins, 532 Hepatitis B, 480 Hepatitis C, 434–435, 480. See also Cirrhosis; Infectious disease exposure, in health-care

worker Hepatoportoenterostomy. See Kasai procedure Hepatopulmonary syndrome (HPS), 238, 360, 808 Hepatorenal syndrome, 238 Hernias definition of, 436 femoral, 436 hiatal, 438–439 incisional, 436 inguinal, 436 repair, 436 (See also Herniorrhaphy) umbilical, 436 Herniated disk, 60 and epidural steroid injection, 377 Herniorrhaphy, 436–437 Hespan, 247. See also Hetastarch hydroxyethyl starch Hetastarch hydroxyethyl starch, 1011 Hextend. See Hetastarch hydroxyethyl starch Hiatal hernia, 438–439 Hiccups, 440–441 High cardiac output (HCO), 172–173 His bundle, 98 Histamine (H1) antagonists, in postoperative nausea and vomiting, 697 HIV, 480 HMG COA reductase inhibitors (statins), 1020–1021. See also Perioperative statins Hofmann elimination, 442–443 Homozygous protein C deficiency, 730 Hormones/hormone analogs/methergine, 1022–1025 Horner syndrome, 113 H2 receptor antagonists, in gastroesophageal reflux disease, 408, 409 Human papillomavirus (HPV), 480 Human plasma-derived concentrate, 68 Hyaline membrane disease, 20 Hydralazine, 1030 blood flow resistance and, 127 in eclampsia, 349 in HELLP syndrome, 423 for intraoperative hypertension, 131 in preeclampsia, 708 Hydrochlorothiazide (HCTZ), 1010 Hydrocodone, 1036 in breastfeeding mothers, 511 Hydrocortisone, 1023 in acute adrenal insufficiency, 17

in hypoaldosteronism, 35 in post-dural puncture headache, 685 Hydrogen sulfide, and systemic vascular resistance, 24 Hydromorphone, 959, 1036 in breastfeeding mothers, 511 Hydroxyethyl starches, 246. See also Colloids 5-hydroxytryptamine-3 receptors, and tardive dyskinesia, 852 Hydroxyzine, 995 Hyoscyamine, in amyotrophic lateral sclerosis, 44 Hyperbaric oxygen (HBO) therapy, 444–445. See also Partial pressures in cyanide poisoning, 307 Hypercalcemia, and EKG changes, 3 Hypercapnia, 501 Hypercarbia, 158, 314 Hyperchloremia, 222 Hypercoagulability during pregnancy, 124–125 Hypercyanotic spells, 637 Hyperglycemia, 446–447 Hyperglycemic hyperosmolar non-ketotic (HHNK) coma, 330, 452–453 Hyperkalemia, 448–449, 706, 707 and EKG changes, 3 Hyperlactatemia, anaerobic metabolism and, 47 Hypermagnesemia, 542 and EKG changes, 3 Hypernatremia, 450–451 Hyperosmolality, 668 Hyperosmolar hyponatremia, 466. See also Hyperglycemic hyperosmolar non-ketotic (HHNK) coma Hyperoxia, 839 Hyperphosphatemia, 658 Hypertension, 454–455 acute, 130 angiotensin and, 56 chronic, 130 essential, 454 intraoperative, 131 perioperative, 644–645 pulmonary, 744–745 secondary, 454 Hypertension, hypervolemia, and hemodilution (triple-H therapy), 212 Hypertensive urgency, 644 Hyperthermia, 456–457. See also Malignant hyperthermia (MH) Hyperthyroidism, 458–459 Hypertonicity, 340

Hypertonic saline, and ICP, 491 Hypertrophic cardiomyopathy (HCM), 460–461 Hypocalcemia, and EKG changes, 3 Hypochloremia, 223 Hypofibrinogenemia, 398 Hypoglycemia, 462–463 Hypokalemia, 464–465, 706, 707 and EKG changes, 3 Hypomagnesemia, 542 and EKG changes, 3 Hyponatremia, 466–467, 669 Hypoosmolality, 669 Hypoosmolar hyponatremia, 466 Hypophosphatemia, 658 in perioperative period, 659 postoperative, 659 Hypotension controlled, 264–265 intraoperative, 130–131 Hypothalamic–pituitary–adrenal (HPA) axis and adrenal insufficiency, 16 Hypothermia, 468–469 Hypothyroidism, 470–471 Hypotonicity, 340 Hypoventilation, 36 Hypoxemia, 386, 626 Hypoxia, 624 with increased A-a gradient and a/A ratio, 36 intraoperative, 472–473 with normal A-a gradient or a/A ratio, 36 postoperative, 692–693 Hypoxic delivery, 36 Hypoxic pulmonary vasoconstriction (HPV), 36, 612, 746, 749, 808, 929. See also One lung ventilation (OLV); Pneumonectomy Hysterectomy, 474–475 abdominal, 474 types, 474 I Ibuprofen, 1034t in breastfeeding mothers, 510 Ibutilide, in atrial flutter, 103 Idiopathic thrombocytopenia purpura (ITP), 862. See also Thrombocytopenia in pregnancy, 124

I:E ratio, 476–477 asthma and, 95, 476 (See also Asthma) IgA deficiency, 478–479 IL-18, 700 Inapsine. See Droperidol Inderal. See Propranolol Indigo carmine, 1013 Indomethacin, in preterm labor, 724 Infantile hypertrophic pyloric stenosis (IHPS). See Pyloric stenosis Infant, premature, 722–723 anemia of prematurity in, 52–53 apnea of prematurity in, 82–83 placenta accreta and, 662 placental abruption and, 666 preeclampsia in (See Preeclampsia) respiratory physiology in, 638–639 retinopathy of prematurity in, 782–783 Infections and thrombocytopenia, 862 transfusion and, 886–887 Infectious disease exposure, in health-care worker, 480–481 Influenza A, 480 Infraglottic jet ventilation, 500 Infrarenal abdominal aortic aneurysms repair, 482–483 Inhalational infections, 480 Inhaled nitric oxide (INO), in ARDS, 21 Inotropes, blood flow resistance and, 126–127 Insensible fluid losses, 484–485 Inspiratory time, 476 Inspra. See Eplerenone Insulin-like growth factor 1 (IGF-1), 14 Insulins, 1023–1024, 1024t in diabetes mellitus, 328 in peripheral vascular disease, 652 Interatrial septum (IAS), 98 Interferon-beta 1α, in multiple sclerosis, 578 International Association for the Study of Pain (IASP), 90, 254 International normalized ratio (INR), 486–487, 732. See also Prothrombin time (PT); Warfarin The International Reflux Study Group (IRSG), 918 International sensitivity index (ISI), 487 International Subarachnoid Aneurysm Trial, 207 Internodal bundles, 98 Interstitial lung disease, 340 Intestinal obstruction, 488–489

Intracardiac shunt, 36, 808 Intracranial abscess, 445 Intracranial hemorrhage, craniotomy for, 288 Intracranial hypertension (ICH), 490–491 Intracranial pressure (ICP), 214 Intralipid. See IV fat emulsion Intraoperative magnetic resonance imaging system (IMRIS), 54 Intraoperative myocardial ischemia, 492–493 Intrapulmonary shunt (IPS), 808–809 Intrarenal acute kidney injury, 496–497 Intravenous (IV) access, 338 difficult, 338–339 Intravenous regional anesthesia (IVRA). See Bier block Intropin. See Dopamine Intubation/extubation criteria, 498–499 Invanz. See Ertapenem Inverse respiratory ventilation (IRV), 476 In vitro contracture testing (IVCT), 545 Ipratropium, 998 Irbesartan, 973t Ischemia, 164 cerebral blood flow in, 204–205 Ischemic optic neuropathy, 642 Isocaine. See Mepivacaine Isocarboxazid, 989t Isoflurane, 1052 and EEG, 357 Isoproterenol, 1043 in bradycardia, 141 Isotonicity, 340 Isovolumetric contraction, 72 Isuprel. See Isoproterenol IV anesthetics and MEPs, 819 and SSEPs, 818 IV antihypertensives, 1030–1031 IV fat emulsion, 1021 in local anesthetic systemic toxicity, 535 J Januvia. See Sitagliptin Jaundice, postoperative, 694–695 Jehovah’s witnesses, and blood transfusion, 425 Jet ventilation, 500–501. See also Difficult airway; Tracheal and cricotracheal resection

J point, 2 Jugular venous oxygen saturation (SjO2), 502–503

Junctional rhythms, 504–505 K

Kallikrein, 162 Kapidex. See Dexlansoprazole Kasai procedure, 506–507 Ketamine, 959, 1027 in breastfeeding mothers, 510 in bronchoscopy, 149 and cerebral metabolic rate, 209 context-sensitive half-time, 260 and EEG, 357 effect on autonomic nervous system, 112 as epidural, 370 in hiccups, 440 and MEPs, 819 in postoperative shivering, 703 Ketoconazole, in Cushing’s syndrome, 304 Ketorolac, 1034t in breastfeeding mothers, 510 Kidney transplantation, 508–509 KIM-1, 700 King LT-D/LTS-D, 836 Klonopin. See Clonazepam Kyphoplasty, 952–953 Kytril. See Granisetron L Labetalol, 1000t in eclampsia, 349 in HELLP syndrome, 423 in intraoperative hypertension, 131 in pheochromocytoma, 656 in preeclampsia, 708 Lactated Ringer’s, 300 Lactation, and anesthesia, 510–511 Lactic acidosis, 46 perioperative, 46 Lactulose, in hepatic encephalopathy, 432 Lagophthalmos, 270 Lambert–Eaton myasthenic syndrome (LEMS), 582–583, 600 Lamictal. See Lamotrigine

Laminar airflow, 512–513 Lamotrigine, 985 Lanoxin. See Digoxin Lansoprazole, 1045 Laparoscopic appendectomies, 84 Laparoscopic-assisted vaginal hysterectomy (LAVH), 474 Laparoscopy, 514–515 Laparoscopy-assisted APR, 8. See also Abdominoperineal resection (APR) Laplace’s law, 4, 24, 32, 38, 39, 333, 586, 587, 636. See also Afterload Laryngeal mask airway (LMA), 836 Laryngeal papillomatosis, 480 Laryngoscopy positioning, 516–517 Laryngospasm, 88, 518–519, 831. See also Superior laryngeal nerve (SLN) Lasix. See Furosemide Latex allergy, 520–521 Law of Laplace. See Laplace’s law Left anterior descending artery (LAD), 272 Left atrium (LA), 98. See also Atria Left bundle branch block (LBBB), 2, 522–523 Left circumflex coronary artery (LCX), 272 Left internal mammary artery (LIMA), 274 Left main coronary artery (LMCA), 272 Left ventricular assist device (LVAD), 550 Left ventricular end-diastolic pressure (LVEDP), 524–525, 524f Lenalidomide in amyloidosis, 42 in multiple myeloma, 576 Lescol. See Fluvastatin Levaquin. See Levofloxacin Levodopa, in Parkinson’s disease, 628 Levofloxacin, 977 Levophed. See Norepinephrine Levothyroxine, 1025 Lewy bodies, 628 Lexapro. See Escitalopram Lidocaine, 971 in Bier block, 120 and cerebral metabolic rate, 209 in hiccups, 440 Linagliptin, 1041t Line isolation monitor (LIM), 353 Linezolid, 976 Lioresal. See Baclofen Lipitor. See Atorvastatin

Lipolysis, 330 Liraglutide, 1041 Lisinopril, 972t Lithium carbonate, 1006. See also Depression Lithobid SR. See Lithium carbonate Liver function tests (LFTs), 526–527. See also Postoperative jaundice Liver resection, 528–529 Liver system, and acid–base buffering system, 151 Liver transplantation, 530–531 Liver vasculature, 532–533 Local anesthetic (LA) toxicity, 534–535 Long-acting beta-agonists, 999, 999t Loop diuretics, 223 Lopressor. See Metoprolol Lorazepam, 959, 1028 in amyotrophic lateral sclerosis, 44 in eclampsia, 348–349 Losartan, 973t Lotensin. See Benazepril Lou Gehrig’s disease, 44–45 Lovastatin, 1020t Low anterior resection (LAR), 8 Lower esophageal sphincter (LES), 88, 438. See also Aspiration; Hiatal hernia Lower extremity bypass, 538–539 Lower extremity (LE) amputation, 536–537 Low molecular weight heparin (LMWH), 1055 before delivery, 125 in pulmonary embolism, 739 Lumbar facet arthropathy, 388 Lumbar subarachnoid catheter, 215 Lung calcifications, and chest x-ray, 221 Lung carcinoma, and chest x-ray, 221 Lusitropy, 540–541 LV end-systolic pressure, 72 Lyrica. See Pregabalin Lysine analogs, action mechanism of, 66 M

Macroshock, 352 Magnesium, 542–543, 1014 in eclampsia, 348 in HELLP syndrome, 423 in preeclampsia, 708 in preterm labor, 724

The Malignant Hyperthermia Association of the United States (MHAUS), 545 Malignant hyperthermia (MH), 195, 456, 544–545 Mannitol, 223, 1010–1011 for lowering ICP, 491 MAO-B inhibitors, in Parkinson’s disease, 628 MAO Inhibitors, 989, 989t Marcaine. See Bupivacaine Marijuana abuse, 546–547, 828 Marinol. See Dronabinol Mastectomy, 548–549 McGill Pain Questionnaire, 91 Mean arterial pressure (MAP), 72, 130 Mechanical circulatory assist devices (MCADs), 550–551 in congestive heart failure, 259, 550 Mechanical ventilation, 86, 92, 345, 498, 678. See also Assist control ventilation (A/C); Intubation/extubation criteria in ARDS, 21 parameters, 92 Median nerve, 138 Mediastinal masses, anterior, 62–63 Mediastinoscopy, 552–553 Mediastinum, widened, and chest x-ray, 220–221 Medication errors, 554–555 Medrol. See Methylprednisolone Mefoxin. See Cefoxitin Meglitinides, in diabetes mellitus, 328 MELD score (Model for End-stage Liver Disease), 238, 360, 433, 530, 894. See also Cirrhosis Melphalan, in amyloidosis, 42 Membrane potential, 194 Mendelson syndrome, 88. See also Aspiration Menkes Disease, 336 Meperidine, 1037 in breastfeeding mothers, 511 in postoperative shivering, 703 Mepivacaine, 971 Messerklinger technique. See Endoscopic sinus surgery Metabolic acidosis, 58, 556–557 high AG, 58 low AG, 58 normal AG, 58 postcardiac surgery, 59 Metabolic alkalosis, 558–559 Metformin, 1040 in peripheral vascular disease, 652

Methadone, 1039 Methemoglobin, 560–561 Methemoglobinemia, 424 Methergine. See Methylergonovine Methimazole, in hyperthyroidism, 458 Methohexital, 959, 1027 Methotrexate (MTX), 1004 Methyldopa, 1031 Methylene blue (MB), 1012 in hypotension, 11 in methemoglobinemia, 561 Methylergonovine, 1024 Methylmethacrylate (MMA), 198 Methylprednisolone, 1023 in ARDS, 21 in multiple sclerosis, 578 Methylxanthines, in apnea of prematurity, 82 Metoclopramide, 992 in aspiration, 88 in gastroesophageal reflux disease, 409, 438 in hiccups, 440 in postoperative nausea and vomiting, 697 and tardive dyskinesia, 852 Metoprolol, 1000t in atrial tachycardia, 107 in pheochromocytoma, 656 Metronidazole, 976 in hepatic encephalopathy, 432 Metyrapone, in Cushing’s syndrome, 304 Mevacor. See Lovastatin Mexiletine, 974–975 Micardis. See Telmisartan Microshock, 352 Midamor. See Amiloride Midazolam, 959, 1028 in aortic regurgitation, 75 in awake craniotomy, 114 in breastfeeding mothers, 510 context-sensitive half-time, 260 Milrinone, 1043 in cardiogenic pulmonary edema, 177 Mineralocorticoids, 16 Minimally invasive aortic valve surgery, 78 Minimum alveolar concentration (MAC), 562–563

Minute ventilation (MV), 564–565 Mirtazapin, in postoperative nausea and vomiting, 697 Mitotane, in Cushing’s syndrome, 305 Mitoxantrone, in multiple sclerosis, 578 Mitral regurgitation (MR), 566–567, 720 acute, 566 chronic, 566 Mitral stenosis (MS), 720 Mitral valve prolapse (MVP), 570–571 Mitral valve replacement, 572–573 Mitral valve stenosis (MS), 568–569 statin therapy and, 648 Mixed expired PCO2 (PETCO2), 363

Mixed venous oxygen saturation (MVO2), 574–575. See also Pulmonary artery catheter

waveform Modafinil, in amyotrophic lateral sclerosis, 44 Model for end-stage liver disease (MELD) score. See MELD score (Model for End-stage Liver Disease) Modification of Diet in Renal Disease (MDRD) formula, for GFR estimation, 419 Monitored anesthesia care (MAC)/sedation cases, and fire risk, 26 Monoclonal gammopathy of undetermined significance (MGUS), 576 Monopril. See Fosinopril Morgagni’s hernia, 257 Morphine, 959, 1036 in amyotrophic lateral sclerosis, 44 in aortic dissection, 71 in breastfeeding mothers, 511 Motor-evoked potentials (MEPs), 818–819. See also Scoliosis repair Motrin. See Ibuprofen Moya-Moya regions, 205 Moyamoya syndrome, 235 Mucociliary clearance (MC), determinants of, 232 Mucolytics (DNAses), in cystic fibrosis, 309 Mucus, 232 MUDPILES, mnemonic, 59 Multidimensional pain scales, 91 Multifocal atrial tachycardia (MAT), 106. See also Atrial tachycardia (AT); Synchronized electrical cardioversion Multiple myeloma, 576–577 Multiple sclerosis (MS), 578–579 Mupirocin, 979 Muscarinic acetylcholine receptors, in SA node, 230 Muscle relaxants, 1032–1033 Muscular dystrophy, 600

Musculocutaneous nerve, 138 Myasthenia gravis (MG), 580–581, 600 Myasthenic syndrome, 580, 582–583 Myocardial contusion, 584–585 Myocardial cooling, 266–267 Myocardial infarction, and chest pain, 686, 687 Myocardial oxygen demand, 586–587 and postoperative chest pain, 686 Myocardial segments, 272 Myocardial wall tension, 586 Myocardium, energy consumption of, 46 Myocytes, 164. See also Cardiac action potential Myonecrosis, 444 Myotonic dystrophy, 600 N

Nabilone (Cesamet), 546 N-acetylcysteine in amyotrophic lateral sclerosis, 44 in ARDS, 21 NADPH-methemoglobin reductase, 561 Nalbuphine, 1038 Naloxone, 1038 in postoperative nausea and vomiting, 697 Naltrexone, 1038 Naprosyn. See Naproxen Naproxen, 1034t Narcotic and cerebral metabolic rate, 209 withdrawal, 588–589 Naropin. See Ropivacaine Narrow-QRS complex tachycardia, 850 Natalizumab, in multiple sclerosis, 578 The National Board of Echocardiography, 494 The National Coordinating Council for Medication Errors Reporting and Prevention, 554 The National Surgical Quality Improvement project, 824 Near infrared spectroscopy (NIRS), 551 Nebcin. See Tobramycin Necrotizing soft tissue infections, 445 Negative pressure pulmonary edema (NPPE), 590–591 and chest x-ray, 221 laryngospasm and, 519 Neomycin, in hepatic encephalopathy, 432 Neonatal alloimmune thrombocytopenia (NAIT), 862. See also Thrombocytopenia

Neonatal distress syndrome (RDS), 38 Neonatal hypoglycemia, 462 Neostigmine, 335, 1049 Neo-synephrine. See Phenylephrine Nephrectomy, 592–593 Nephrons, 292, 704 Nernst Equation, 194 Nerve decompression, 60 Nerve fascicles, 138 Nesacaine. See Chloroprocaine Neuraxial anesthesia, 214 Neuraxial blocks, 113 Neuraxial local anesthetics, 215 Neuraxial opioids, 215 Neurofibromatosis (NF), 594–595 Neurogenic pulmonary edema (NPE), 596–597 Neurogenic shock, 598–599 Neurokinin (NK1) antagonists, in postoperative nausea and vomiting, 697 Neuroleptic malignant syndrome (NMS), 456. See also Hyperthermia Neuromuscular junction (NMJ), 600–601 Neuronal resting membrane potential, 222 Neurontin. See Gabapentin Neutral “in-line” position, laryngoscopy, 516, 516f Neutrophil gelatinase-associated lipocalin (NGAL), 700 Nicardipine, 1002t in aortic dissection, 71 in intraoperative hypertension, 131 NICE SUGAR study, 462 Nicotine replacement therapy, 816 Nifedipine, 1002t in eclampsia, 349 in HELLP syndrome, 423 in preeclampsia, 708 in preterm labor, 724 Nimodipine, 1002t in cerebral vasospasm, 212 Nimotop. See Nimodipine Nipride. See Nitroprusside Nitrates, in angina, 226 Nitric oxide (NO), 1046 and systemic vascular resistance, 24 Nitroglycerine, 1030 in abdominal aortic aneurysms, 5 in cardiogenic pulmonary edema, 177

in intraoperative hypertension, 131 Nitroprusside, 1030 in cardiogenic pulmonary edema, 177 in intraoperative hypertension, 131 Nitrous oxide, 1053 and cerebral metabolic rate, 209 and EEG, 357 and MEPs, 819 and SSEPs, 818 Nitrovasodilators, blood flow resistance and, 127 Nizatidine, 1018 N-methyl-D-aspartate receptors antagonists in complex regional pain syndrome, 253 in Parkinson’s disease, 628 Noncardiogenic pulmonary edema (NCPE), 602–603 Nondepolarizing muscle relaxants, and cerebral metabolic rate, 209 Non-invasive blood pressure (NIBP) cuff, 604–605 Nonobstructive hydrocephalus, 214 Norepinephrine, 1042 in aortic dissection, 71 blood flow resistance and, 127 in cardiogenic pulmonary edema, 177 and cerebral metabolic rate, 209 in intraoperative hypotension, 131 Normal saline, 300 Normosol, 300 Normovolemic hemodilution. See Acute normovolemic hemodilution (ANH) Norpace. See Disopyramide Norpramin. See Desipramine Nortriptyline, 987t Norvasc. See Amlodipine Novacaine. See Procaine NSAIDs, 1034–1035, 1034t in CRPS Type II, 255 in rheumatoid arthritis, 788 Numeric rating scale (NRS), 90 Nupercaine. See Dibucaine O Obesity, 118. See also Bariatric surgery medical problems with, 118 and tidal volume, 867 Obesity–hypoventilation syndrome (OHS), 564–565, 606–607 Obstructive sleep apnea (OSA), carotid body and, 182

Occipital infarct, 642 Octreotide in carcinoid, 163 in gastrectomy, 407 Oculocardiac reflex (OCR), 608–609 Off-pump coronary artery bypass grafting (OPCABG), 276–277 Ofirmev. See Acetaminophen Ohm’s law, 126, 127, 352 Ohtahara syndrome, 156 Olanzapine, 1007t in postoperative delirium, 691 Olmesartan, 973t Omeprazole, 1044 Omphalocele, 610–611 Ondansetron, 990 in carcinoid, 163 in postoperative nausea and vomiting, 697 One lung ventilation (OLV), 342, 612–613, 678, 749 Onglyza. See Saxagliptin Operating room (OR) electrical safety in, 352–353 fire, 614–615 Opiates, effect of alcohol on, 28 Opioid abuse, 828 Opioids and analgesics, 1036–1039 in complex regional pain syndrome, 253 in CRPS Type II, 255 and EEG, 357 effect on autonomic nervous system, 112 as epidural, 370 and MEPs, 819 in postoperative shivering, 703 Opioid withdrawal, 588. See also Narcotic withdrawal Oral agents for type 2 DM, 1040–1041 Oraverse. See Phentolamine Organ Procurement and Transplantation Network, 142 Orthopedic surgery, antifibrinolytics in, 67 Orthotopic liver transplantation (OLT), antifibrinolytics in, 66–67 Osmitrol. See Mannitol Osmolal gap, 669 Osmolality, 668 Osmolarity, 668 Osmoles, 668

Osmosis, 340 Osteomyelitis, 445 Out-of-OR standards, for anesthesia delivery, 54 Oxidative phosphorylation, 46 Oxycodone, 1036 Oxygen analyzers, on anesthesia machines, 616–617 Oxygen–hemoglobin dissociation curve, 128, 129f, 624 Oxygen, in blood, 128. See also Blood oxygen-carrying capacity Oxygen saturation, 625 Oxygen toxicity, 618–619, 833, 842 Oxyglobin, 132 Oxytocin, 1022 Oxytocin antagonist, in preterm labor, 724 P

Pacemaker cells, 164, 174–175, 230. See also Cardiac action potential Pacemaker dependent, 620–621 Pacemaker implantation, in sick sinus syndrome, 810 Paclitaxel. See Taxanes Pain acute, 90 chronic, 90 definition of, 90 postoperative, assessment of, 90–91 scales, 90–91 Palonosetron, 991 Pamelor. See Nortriptyline Pancreatic cancer, and celiac plexus block, 192 Pancreatic transplantation, 622–623 Pancuronium, 959, 1032 Pantoprazole, 1044 PaO2, 624–625 Parasympathetic nervous system (PNS), 112 Parathyroidectomy, 626–627 Parenteral infections, 480 Parkinson’s disease, 628–629 Paroxetine, 986t Partial anomalous pulmonary venous return (PAPVR), 98 Partial CO2 rebreathing (NiCO2) technique, 170

Partial exchange blood transfusion (PEBT), 727 Partial pneumothorax, and chest x-ray, 220 Partial pressures, 630–631 Partial thromboplastin time (PTT), 632–633

Partition coefficient, 630 Pasteur Effect, 46 Patent ductus arteriosus (PDA), 634–635 Patent foramen ovale (PFO), 98, 104, 650 Patient-controlled analgesia (PCA), in open adrenalectomy, 23 PAT (Paddington Alcohol Test), 30 Pattern recognition receptors (PRRs), 806 Paxil. See Paroxetine Pediatric cardiac physiology, 636–637 Pediatric respiratory physiology, 638–639 Penicillin G, 978 Penicillins, 978 Pentoxifylline, in peripheral vascular disease, 652 Penumbra, 600 Pepcid. See Famotidine Percutaneous coronary interventions (PCI), 166 and coronary artery bypass surgery, 166 Percutaneous transluminal coronary angioplasty (PTCA), 166 Perfluorocarbon-based oxygen carriers (PFBOCs), 132 Perfluorocarbon emulsions (PFCs), 129 Perforated viscus, and chest pain, 686 Pericardial sac, 640 Pericardial tamponade, 640–641 Perioperative blindness, 642–643 Perioperative hypertension, 644–645 Perioperative seizures, 646–647 Perioperative statins, 648–649 Perioperative stroke, 650–651 Peripheral autonomic nervous system, angiotensin II effect on, 56 Peripheral vascular disease (PVD), 112, 652–653 Peritonsillar abscess, 784–785 Perphenazine, and tardive dyskinesia, 852 Persistent fetal circulation. See Persistent pulmonary hypertension of the newborn (PPHN) Persistent pulmonary hypertension of the newborn (PPHN), 394 Phaco, 188 Phacofracture, 188 Phenelzine, 989t Phenergan. See Promethazine Phenoxybenzamine, in pheochromocytoma, 656 Phentolamine, 1031 in pheochromocytoma, 656 Phenylephrine, 1042 in aortic dissection, 71 blood flow resistance and, 126

in hypotension, 11 in intraoperative hypotension, 131 Phenytoin, 985 in eclampsia, 348 in HELLP syndrome, 423 in multiple sclerosis, 578 Pheochromocytoma, 656–657 adrenalectomy for, 22–23 pH measurements, 654–655 Phosphate, 150, 658–659 Phosphodiesterase inhibitors blood flow resistance and, 127 hypotension by, 25 in pulmonary hypertension, 744 Phosphorous, 1015 Phrenic nerve blocks, 216 pH stat management, 654 Physiologic dead space, 314 Physostigmine, 1048 in postoperative shivering, 703 PICC lines, 200 Pickwickian syndrome, 564–565. See also Obesity-hypoventilation syndrome (OHS) Pierre Robin sequence, 336, 660–661 Pierre Robin syndrome. See Pierre Robin sequence Pioglitazone, 1040 Pipecuronium, 1032–1033 Pitocin. See Oxytocin Pitressin. See Vasopressin Pituitary tumor, overproduction of GH by, 14. See also Acromegaly Placenta accreta, 662–663. See also Placenta previa Placental abruption, 666–667 Placenta previa, 664–665 and risk of placenta accreta, 664 (See also Placenta accreta) Plasma cells, 42 Plasma exchange, 576 Plasmalyte, 300 Plasma osmolality, 668–669 Plasma osmolarity, 301 Plasmapheresis, 670 Plasminogen, 66 Platelet factor 4 (PF4), 430 Platelets, 670–671 Platelet transfusion, in thrombocytopenia, 863 Platinating agents (cisplatin, carboplatin, oxaliplatin), 1005

Plavix. See Clopidogrel Plendil. See Felodipine Pneumonectomy, 672–673 Pneumothorax, 674–675 and chest pain, 686 POEMS syndrome, 576 Poiseuille’s law, 126, 127 Polocaine. See Mepivacaine Polycythemia, 424, 676–677 primary, 676 secondary, 676 Pooled platelet, 670 Port-a-cath, 200 Portal hypertension, 238, 532. See also Cirrhosis Portal vein, 532 Positive end expiratory pressure (PEEP), 39, 678–679 extrinsic, 678 intrinsic, 678 physiologic, 678 Postdural puncture headache (PDPH), 214, 251, 370, 684–685 Posterior ischemic optic neuropathy, 642 Post-heart transplant, 680–681 Postoperative chest pain, 686–687 Postoperative cognitive dysfunction (POCD), 688–689 Postoperative delirium, 690–691 Postoperative hypoxia, 692–693 Postoperative jaundice, 694–695 Postoperative nausea and vomiting (PONV), 696–697 Postoperative pulmonary complications (PPCs), 698–699 Postoperative renal dysfunction, 700–701 Postoperative shivering, 702–703 Postrenal acute kidney injury, 704–705 Post-tonsillar bleed, 682–683 Post-transfusion thrombocytopenia, 862. See also Thrombocytopenia Potassium, 706–707 Potassium iodide, in hyperthyroidism, 458 Potassium-sparing diuretics, 1010, 1011t Prasugrel, 1050t Pravachol. See Pravastatin Pravastatin, 1020t Prazosin, 1031t in pheochromocytoma, 656 Prednisone, in amyloidosis, 42 Preeclampsia, 708–709

Pregabalin, 984 in complex regional pain syndrome, 253 Pregnancy associated thrombocytopenia, 862 blood coagulation physiology in, 124–125 and tidal volume, 867 Pregnancy-induced hypertension (PIH), 710–711 Preload, 712–713, 848 Premature atrial contractions (PACs), 714–715 Premature infant pain profile (PIPP), 91 Premature ventricular contractions (PVCs), 716–717, 941 Preoperative autologous blood donation (PABD), 108 Prerenal acute kidney injury, 718–719 Pressor agents, 1042–1043 Pressure-controlled ventilation (PCV), 476 Pressure decay, 86 Pressure support ventilation (PSV), 499 Pressure–volume loops, 332, 720–721 Preterm infant, 722–723 Preterm labor, 724–725 Prevacid. See Lansoprazole Prilocaine, 971 in Bier block, 120 Prilosec. See Omeprazole Primary adrenal insufficiency (PAI), 16. See also Acute adrenal insufficiency Primary hyperadrenalism, 304 Prinivil. See Lisinopril PR interval, 2 Prion diseases, transmission of, 480 Pro-Air. See Albuterol Procainamide, 974t in atrial flutter, 103 Procaine, 1016 Procardia. See Nifedipine Prochlorperazine, 993 and tardive dyskinesia, 852 Procysteine, in ARDS, 21 Prolonged QT interval, 165 Promethazine, 993 Promotility agents, in gastroesophageal reflux disease, 409 Pronestyl. See Procainamide Propafenone, 975, 975t in atrial flutter, 103 Propofol, 959, 1026

in alcohol withdrawal syndrome, 31 and cerebral metabolic rate, 208 context-sensitive half-time, 260 effect on autonomic nervous system, 112 and egg allergy, 49 in hiccups, 440 and MEPs, 819 Propofol infusion syndrome (PRIS), 726–727 Propranolol, 1000t Propylthiouracil (PTU), in hyperthyroidism, 458 Prostaglandin synthetase inhibitors, in preterm labor, 724 Prostatectomy, 728–729 laparoscopic, 728 open, 728 robotic assisted, 728 trans-urethral, 728 Protamine, 983 Protein C, 730–731 Prothrombin time (PT), 732–733 Protonix. See Pantoprazole Proton pump inhibitors, 1044–1045 in gastroesophageal reflux disease, 408, 409 in GERD, 438 in hiccups, 440 Proventil. See Albuterol Prozac. See Fluoxetine Pseudocholinesterase, 334 Pseudohyperkalemia, 449 Pseudothrombocytopenia, 862 Pulmonary artery catheter continuous cardiac output (PAC CCO), 170 Pulmonary artery catheter thermodilution method (PAC TD), 170, 173 Pulmonary artery catheter waveform, 734–735 Pulmonary artery pressure (Ppa), 38 Pulmonary artery wedge pressure (PAWP), 524–525 Pulmonary atresia, 736–737 Pulmonary autograft (Ross procedure), 78 Pulmonary circulation, 38 Pulmonary edema, 746–747 and chest x-ray, 221 Pulmonary embolism (PE), 738–739 and chest pain, 686 in pregnancy, 124 Pulmonary fibrosis, 39 Pulmonary function tests (PFTs), 308, 740–741

Pulmonary gases, 1046–1047 Pulmonary hemorrhage, 742–743 Pulmonary hypertension (PH), 744–745 Pulmonary shunt, 36 Pulmonary vascular resistance (PVR), 24 blood flow resistance and, 126 Pulmonary vasculature, 746–747 Pulmonary venous pressure (Ppv), 38 Pulmonary ventilation–perfusion matching, 748–749 Pulse contour analysis-based methods, for CO measurement FloTrac/Vigileo system, 171 LiDCO system, 171 PiCCO system, 171 Pulse dye densitometry, 170 Pulseless electrical activity (PEA), 752–753 Pulse oximetry, 625, 750–751 Pulse pressure, 130 Pulsus paradoxus, 219, 640 Purkinje fibers, 174 P wave, 2 Pyloric stenosis, 754–755 Pyridostigmine, 1049 Q QRS width, 2 QT interval, 2 QT prolongation, 2, 756–757 Quantitative sensory testing (QST), 252 Quetiapine, 1007t in alcohol withdrawal syndrome, 31 in postoperative delirium, 691 Quinapril, 972t Quinidine, 974t in amyotrophic lateral sclerosis, 44 R Rabeprazole, 1045 Radial artery, 86 Radial nerve, 138 Radiation safety, 758–759 Radical neck dissection, 760–761 Radiofrequency lesioning, 193 Ramipril, 972t Ramped position, laryngoscopy, 516, 516f

Ranitidine, 1018 in anaphylaxis, 49 in gastroesophageal reflux disease, 409 Ranolazine, in premature atrial contractions, 715 Rapid sequence intubation (RSI), 490 Rasagiline, 989t in Parkinson’s disease, 628 Raynaud’s phenomenon (RP) , 112, 762–763 Reactive oxygen species (ROS), 618 Recombinant activated factor VII (rFVIIa), 41, 429, 764–765 Recombinant human concentrate, 68 Rectacaine. See Dibucaine Rectal cancers, curative procedure for, 8. See also Abdominoperineal resection (APR) Recurrent laryngeal nerve (RLN), 766–767, 956. See also Parathyroidectomy; Thyroidectomy; Vocal cord (VC) palsy Red man syndrome, 976 Reflex sympathetic dystrophy (RSD), 112 Refractory hypotension, 10 Regitine. See Phentolamine Reglan. See Metoclopramide Remifentanil, 959, 1037–1038 in breastfeeding mothers, 510 in bronchoscopy, 149 context-sensitive half-time, 260 Renal blood flow (RBF), 768–769 Renal protection, statin therapy and, 648 Renal system, and acid–base buffering system, 150 Renin, 56 Renin–angiotensin–aldosterone system (RAAS), 56, 57 role of, 10 Renin–angiotensin system (RAS), aldosterone regulation by, 34 Rescue echocardiography, 770–771 Residual volume (RV), 242, 772–773 Respiratory alkalosis, 774–775 Respiratory system, acid–base buffering system and, 150 Respiratory system compliance, 776–777 Retained placenta removal, 778–779 Retinal detachment (RD), 780–781. See also Retinopathy of prematurity (ROP) combined tractional/rhegmatogenous, 780 exudative, 780 rhegmatogenous, 780 tractional, 780 Retinopathy of prematurity (ROP), 618, 782–783 Retrograde cerebral perfusion (RCP), 236

Retropharyngeal abscess, 784–785 Reversal agents, 1048–1049 Revonto. See Dantrolene Reynolds number, 512 The Rheos Multicenter Feasibility Trial, 186 Rheumatoid arthritis (RA), 788–789 Rh factor, 786–787 Rh incompatibility, 786 Rifaximin, in hepatic encephalopathy, 432 RIFLE criteria, of AKI, 705 Right atrium, 98. See also Atria Right bundle branch block (RBBB), 2, 790–791 Right coronary artery (RCA), 272 Right ventricular assist device (RVAD), 550 Riluzole, in amyotrophic lateral sclerosis, 44 Risperdal. See Risperidone Risperidone, 1007t Ritodrine, in preterm labor, 724 Robotic–Da Vinci hysterectomy, 474 Rocuronium, 959, 1032 Ropivacaine, 971 Rosuvastatin, 1020t Rotator cuff surgery, 792–793 Roux-en-Y gastric bypass (RYGB), 118–119 Ruptured abdominal aortic aneurysms (rAAA), 6–7 anesthetic goals/guiding principles, 6 intraoperative care anesthesia, choice of, 6 extubation/emergence, 7 induction/airway management, 7 maintenance, 7 monitoring, 6–7 postoperative care, 7 preoperative assessment, 6 preoperative preparation, 6 Rythmol. See Propafenone S

Sacroiliac (SI) joint injection, 794–795 SAFE study, 301 Saline hypertonic, 300, 301 normal, 300 Salivary estriol, 725

Salmeterol, 999, 999t SA nodal artery disease, 140 Sarcoidosis, 796–797 Sarcoplasmic reticulum calcium ATPase (SERCA), 540 Saxagliptin, 1041t Scandonest. See Mepivacaine Schwannomatosis, 594. See also Neurofibromatosis Schwartz formula, for GFR estimation, 419 Sciatica, and epidural steroid injection, 377 Sciatic nerve block, 798–799 Scleroderma, 800–801 Scoliosis repair, 802–803 Scopolamine, 981 in postoperative nausea and vomiting, 697 Scottie-dog view, 389 Secondary adrenal insufficiency (SAI), 16. See also Acute adrenal insufficiency Seizures, 804–805 perioperative, 646–647 Selective serotonin reuptake inhibitors (SSRIs), 986, 986t Selegiline, 989t in Parkinson’s disease, 628 Sellick maneuver, 88 Sensorcaine. See Bupivacaine Sentinel lymph node biopsy, 548 Sepsis, 806, See also Acute respiratory distress syndrome (ARDS) statin therapy and, 648 Septic shock, 806–807 hyperlactatemia and, 47 Septocaine. See Articaine Septra. See Trimethoprim/sulfamethoxazole (TMP/SMX) Septum secundum ASD, 98 Serevent. See Salmeterol Seroquel. See Quetiapine Serotonin, 162 effect of alcohol on, 28 Serotonin (5-HT3) antagonists, in postoperative nausea and vomiting, 697 Serotonin-5HT-1-A-receptor antagonists, in hiccups, 440 Serotonin norepinephrine reuptake inhibitors (SNRIs), 986–987, 986t in CRPS Type II, 254 C-serotonin release assay (SRA), 431 Sertraline, 986t Sevoflurane, 1052 and EEG, 357 Shivering, postoperative, 702–703

Shunt dead space, 314 Shunt fraction/venous admixture, 808 Shunt, intrapulmonary, 808–809 Sickle cell disease (SCD), 424, 812–813 Sick sinus syndrome (SSS), 140, 174, 810–811 Sildenafil, in Raynaud’s phenomenon, 762 Simvastatin, 1020t Sinoatrial (SA) node, 98, 174 Sinus bradycardia, 99, 140 Sinus node dysfunction, 174 Sinus node fibrosis, 140 Sinus tachycardia, 99 Sinus venosus ASD, 98 Sitagliptin, 1041t Sjögren syndrome, 789 Skin grafts and flaps, 445 Smallpox, 480 Smoke inhalation injury, 306, 814–815. See also Cyanide poisoning Smoking, 816–817 Sniffing position, laryngoscopy, 516, 516f Society of Thoracic Surgeons (STS) registry, 78 Soda lime, 158–159 Sodium bicarbonate, 1014–1015 Sodium citrate, 1019 in aspiration, 88 with citric acid, 1019 with potassium citrate and citric acid, 1019 Sodium nitroprusside (SNP), 306 in aortic dissection, 71 Solubility, 624 Solu-Cortef. See Hydrocortisone Solu-Medrol. See Methylprednisolone Soma. See Carisoprodol Somatosensory-evoked potentials (SSEPs), 818–819 Sotalol, 975 in atrial flutter, 103 Spasmodic panting, 88 Spectral Entropy (M-entropy), 356 Spinal cord, 374 Spinal shock, 820–821 Spinal stenosis, and epidural steroid injection, 377 Spiriva. See Tiotropium Spirometry, 822–823 Spironolactone, 1010, 1010t

Splanchnic circulation, 410. See also Gastrointestinal blood flow Splenectomy, 824–825 laparoscopic, 824 open, 824 Spondylolysis, and epidural steroid injection, 377 Spontaneous breathing test (SBT), 498–499 Stable angina, 226 Starling’s law of capillary filtration, 382 Statins, 648 in abdominal aortic aneurysms, 4 in atrial fibrillation, 101 perioperative, 648–649 in peripheral vascular disease, 652 Stem cells, 134 Steroids in asthma, 95 as epidural, 370 in postoperative nausea and vomiting, 697 Streptokinase in pulmonary embolism, 739 Stress, 24 Strokes perioperative, 650–651 statin therapy and, 648 ST segments, electrocardiography and, 2 Subclavian steal syndrome, 235, 826–827 Substance abuse and pregnancy, 828–829 Succinylcholine, 335, 959, 1032 Sucralfate, 1019 Sudden infant death syndrome, carotid body and, 182 Sufentanil, 959, 1037 in breastfeeding mothers, 511 context-sensitive half-time, 260 Sulfonylureas, 1040 in diabetes mellitus, 328 Sumatriptan, in post-dural puncture headache, 684 Superficial cervical block, 216 Superior laryngeal nerve (SLN), 830–831. See also Vocal cord (VC) palsy Superior vena cava (SVC) syndrome, 62 Supine hypotension syndrome, 80 Supplemental oxygen, 832–833 Supraceliac/suprarenal AAA repair, 834–835 Supraglottic devices, 337, 836–837 Supraglottic jet ventilation (SJV), 500

Supraventricular tachycardia (SVT), 99 Surfactants, alveoli, 38 Surgical Care Improvement Project (SCIP), 838 Surgical fires, 26. See also Airway fires Surgical site infection (SSI), 838 prevention of, 838–839 Surgical trauma, 650 Sympathetic blocks, 113 Sympathetic nervous system (SNS), 112 Synchronized electrical cardioversion, 840–841 Synchronized intermittent mandatory ventilation (SIMV), 842–843 Syndrome of inappropriate antidiuretic hormone (SIADH), 64, 669, 844–845 Synthetic agonists, use of, 65 Synthroid. See Levothyroxine Systemic inflammatory response syndrome (SIRS), CPB and, 180 Systemic lupus erythematosus (SLE), 846–847 Systemic vascular resistance (SVR), 24, 72 blood flow resistance and, 126 Systole, 848–849 Systolic dysfunction, 720 T Tachycardia, 850–851 Tachycardia–bradycardia syndrome, 140 Tagamet. See Cimetidine Tambocor. See Flecainide Tamsulosin, 1031t Tapentadol, 1039 Tardive dyskinesia (TD), 852–853 Taxanes, 1005 Tear production, 270 TEE. See Transesophageal echocardiography (TEE) Tegretol. See Carbamazepine Telmisartan, 973t Temporary occlusion, of radial artery, 86 Tenormin. See Atenolol Tension pneumothorax, and chest x-ray, 220 Terazosin, 1031t Terbutaline, 998 in preterm labor, 724 Terlipressin, in hypotension, 11 Tetracaine, 1017 Tetralogy of Fallot (TOF), 854–855 Teveten. See Eprosartan

Thalassemias, 424, 856–857. See also Hemolytic anemia alpha, 857 beta, 857 Thalidomide, in multiple myeloma, 576 THAM (trome thamine), 151 Theophylline, 999 in asthma, 95 in chronic bronchitis, 228 in post-dural puncture headache, 684 in sick sinus syndrome, 810 Thermal burns, 445 Thiamine, in alcohol withdrawal syndrome, 31 Thiazide diuretics, 223 Thiazolidinediones, in diabetes mellitus, 328 Thienopyridines/ADP inhibitors, 1050–1051, 1050t Thiopental, 959, 1026 and MEPs, 819 Thoracic aortic aneurysm (TAA) repair, 860–861 Thrombate III. See Human plasma-derived concentrate Thrombin inhibitors, in pulmonary embolism, 739 Thrombocytopenia, 670, 862–863 Thrombocytosis, 670 Thromboembolism, in pregnancy, 124 Thrombolysis in myocardial infarction (TIMI) risk score, 278 Thrombolytic therapy, in pulmonary embolism, 739 Thrombosis, 86 Thrombotic thrombocytopenia purpura (TTP) in pregnancy, 124 Thyroidectomy, 864–865 Thyroid storm, 459 Ticlid. See Ticlopidine Ticlopidine, 1050t Tidal volume (TV), 866–867 Tiotropium, 999 Tissue edema, 340 Tissue plasminogen activator (tPA), 66 Tizanidine, 996 in amyotrophic lateral sclerosis, 44 Tobacco exposure, 828 Tobramycin, 977 Tocolytics, 724 Tolcapone, in Parkinson’s disease, 628 Tonicity, 340, 668 Tonsillectomy and adenoidectomy (T&A), 868–869

Tooth, structure of, 322 Topamax. See Topiramate Topiramate, 984 Toprol. See Metoprolol Toradol. See Ketorolac Total anomalous pulmonary venous return (TAPVR), 98 Total body water (TBW), 246, 668 Total laparoscopic hysterectomy, 474 Total lung capacity (TLC), 870–871 Total spinals, 872–873 Toxic multinodular goiter, 458 Tracheal and cricotracheal resection, 874–875 Tracheal stenosis, 512, 876–877. See also Laminar airflow Tracheoesophageal fistula (TEF), 878 repair, 878–879 Tracheostomy, 315, 499, 876, 880–881. See also Difficult airway; Laminar flow; Tracheal stenosis Tradjenta. See Linagliptin Tramadol, 1039 in postoperative shivering, 703 Trandate. See Labetalol Tranexamic acid (TA), 66, 663. See also Antifibrinolytics Transcatheter aortic valve replacement, 78 Transcranial Doppler (TCD), 882–883 in cerebral vasospasm, 212, 213 Transcutaneous blood gas analysis, 654 Transcutaneous (TCP)/transvenous pacing in bradycardia, 141 Transducers, 884–885 Transesophageal echocardiography (TEE). See also Rescue echocardiography in aortic dissection, 70, 71 in aortic valve replacement, 79 for CO measurement, 170, 173 intraoperative, 494–495, 551 Transfusion blood, 129 of cryoprecipitate, 298 of fresh frozen plasma (FFP), 402–403 platelet, 670 Transfusion-associated circulatory overload (TACO), 133 Transfusion infections, 886–887 Transfusion-related lung injury (TRALI), 132, 888–889 Transient intraoperative anemia, 18 Transient ischemic attacks (TIAs), 890–891

Transient neurologic symptoms (TNS), 892–893 Transitional syndrome, 61 Transjugular intrahepatic portosystemic shunt (TIPS), 533, 894–895 Transplantation heart, 420–421 kidney, 508–509 liver, 530–531 pancreas, 622–623 Transpulmonary thermodilution (TPCO), 170 Transsphenoidal pituitary resection, 896–897 Transtracheal jet ventilation (TTJV), 500 Transurethral resection of the prostate (TURP) syndrome, 301 Tranylcypromine, 989t Trauma, 898–899 Treacher Collins Syndrome, 336 Treadmill stress test (TMST), 900–901 Triamterene, 1010 Tricuspid atresia (TA), 902–903 Tricyclic antidepressants (TCA), 987, 987t in complex regional pain syndrome, 252 in CRPS, 254 Tricyclic antidepressants toxicity, and EKG changes, 3 Trimethoprim/sulfamethoxazole (TMP/SMX), 979 Trismus, 904–905 Tropisetron, in postoperative nausea and vomiting, 697 Tuberculosis, 480 Tube thoracostomy, 218. See also Chest tubes Tunneled catheters, 200 TURP syndrome, 906–907 T wave, 2 12-lead EKG, 2–3 Tylenol. See Acetaminophen U Ulcerative colitis, 908–909, 910 Ulnar artery, 86 Ulnar nerve, 138 Ulnar neuropathy, 910–911 Umbilical cord prolapse, 912–913 Unasyn. See Ampicillin/Sulbactam Undersea and Hyperbaric Medicine Society, 444 Upper esophageal sphincter (UES), 88 Upper respiratory infection (URI), preoperative, 914–915 Uremia, 916–917

Ureteral reimplantation, 918–919 Ureteroscope, 310 Urine osmolality, 920–921 Urine output (UO), 922–923 Urokinas, in pulmonary embolism, 739 USEDCARP, mnemonic, 59 Uterine blood flow (UBF), 924–925 Uterine rupture, 926–927 Uterine tachysystole, 925 V

VACTERL syndrome, 878 Vaginal delivery, 930–931 Valproic acid, 984 Valsartan, 973t Valvular function, 932–933 Vancocin. See Vancomycin Vancomycin, 976 Vascular compliance, 934–935 Vasodilators in aortic dissection, 71 blood flow resistance and, 127 Vasopressin, 10, 1022. See also ACLS anesthetic management; Antidiuretic hormone (ADH) blood flow resistance and, 127 in hypotension, 11 use of, 65 Vasopressors blood flow resistance and, 126–127 in septic shock, 807 Vasotec. See Enalapril Vecuronium, 959, 1032 Venlafaxine, 986t Venous admixture, normal, 36 Venous air embolism (VAE), 936–937 Ventilation-perfusion (V/Q) mismatch, 36 Ventilation, physiologic control of, 92 Ventilator-associated pneumonia (VAP), 938–939 Ventolin. See Albuterol Ventricles, 940–941 Ventricular afterload, 24–25 dynamic component, 24 static component, 24 Ventricular fibrillation (VF), 942–943. See also ACLS anesthetic management; Hyperkalemia Ventricular hypertrophy, 944–945. See also Afterload; Aortic stenosis; Hypertrophic

cardiomyopathy Ventricular septal defect (VSD), 941, 946–947 Ventricular tachycardia (VT), 941, 948–949 Ventriculogram, 166 Ventriculo-peritoneal (VP) shunt, 950–951 Ventriculostomy, 215 Verapamil (Calan, Isoptin), 1103t in atrial flutter, 103 in atrial tachycardia, 106 Verbal descriptor scale (VDS), 90 Vertebroplasty, 952–953 Vibramycin. See Doxycycline Victoza. See Liraglutide Video-assisted thoracoscopic surgery (VATS), 954–955 Vinca alkaloids (vinblastine, vinorelbine), 1005 Vincristine, 1005 in amyloidosis, 42 in multiple myeloma, 576 Vision loss after nonocular surgery, 642–643 Vistaril. See Hydroxyzine Visual Analogue Scale (VAS), 90 Vital capacity maneuver (VCM), 97 Vitamin K, 1055 Vivacaine. See Bupivacaine Vocal cord (VC) palsy, 956–957 Volatile agents. See Volatile anesthetics Volatile anesthetics, 1052–1053 in asthma, 95 and cerebral metabolic rate, 209 effect on autonomic nervous system, 113 and MEPs, 819 and SSEPs, 818 Voltaren. See Diclofenac Volume-controlled ventilation, 476 Volume of distribution (Vd), 958–959 von Willebrand’s disease (vWD), 960–961. See also Fibrinogen V/Q mismatching, 928–929 W Wall stress, 24 Warfarin, 1054 and prothrombin time, 733 in pulmonary embolism, 739 in sick sinus syndrome, 810

Wellbutrin. See Bupropion Wet tap, 215, 251 Whipple procedure, 962–963 Wolff–Parkinson–White syndrome (WPW), 964–965 Work of breathing, 966–967 X

Xenon, 1046 Xylocaine. See Lidocaine Y

Yersinia pestis, 480 Z Zanaflex. See Tizanidine Zantac. See Ranitidine Zestril. See Lisinopril Ziprasidone, 1007t Zocor. See Simvastatin Zofran. See Ondansetron Zoloft. See Sertraline Zorcaine. See Articaine Zostrix. See Capsaicin Zygapophysial arthropathy, 388 Zyprexa. See Olanzapine Zyvox. See Linezolid

See Table Ingested material Minimum fasting period Clear liquid

2 hours

Breast milk

4 hours

Infant formula

6 hours

Non-human milk

6 hours

Light meal

6 hours

Drugs used for intraoperative hypotension Drug

Receptor

Phenylephrine α1

Dose 50-100 meg bolus (adult) 0.15-0.75 meg/kg/min

Norepinephrine α1,2; β1 0.01-0.1 meg/kg/min Epinephrine

α1,2; β

0.01-0.03 meg/kg/min

Ephedrine

α1; β1,2 5-10 mg bolus (adult)

Dopamine

α; β; D1

2-10mcg/kg/min

Dobutamine

β1,2

2-30 meg/kg/min

Drugs used for intraoperative hypertension Drug

Peak effect Duration

Dose

Esmolol

2-5 min

2-5 min

50-200 mcg/kg/min

Labetalol

5-15 min

2-6 hrs

10-20 mg bolus over 2 min

Hydralazine

15-20 min

3-4 hrs

5-10 mg bolus every 15 min, up to 40 mg

Nitroprusside Immediate 2-5 min

0.3-1.0 mcg/kg/min

Nitroglycerine Immediate 2-5 min

5-100 mcg/kg/min

Nicardipine

5-60 min

20-40 min 2.5 mg over 5 min, infusion 5-15 mg/hr

Diltiazem

3-30 min

3 hrs

10-20 mg/hr

See Table Formation Roots

Trunks

Subdivisions

After leaving the intervertebral foramina, at

Divisions Below the clavicle

distribution C5-T1

the transverse process, ventral rami combine Anterior and middle scalene muscles

Nerve

Superior

C5-C6

Inferior

C8-T1

Middle

C7

Anterior/upper Anterior/middle Anterior/lower

Posterior/upper Posterior/middle Posterior/lower Posterior (upper and lower subscapular, thoracodorsal, axillary, radial)

Cords

Below the clavicle

Lateral (lateral pectoral, musculocutaneous, lateral root of the median nerve)

Medial (medial pectoral, medial cutaneous nerve of the arm and forearm, ulnar nerve)

C5-T1

C5-C7 C8-T1

Table 1. Comparison of adult versus pediatric cardiopulmonary bypass CPB Parameter

Adult

Pediatric

Temperature

Rarely below 30°C

Commonly below 30°C

Circulatory arrest

Rarely used

Commonly used

Dilutional effect of pump prime

25-30%

150-300%

Additives to pump prime

Blood only occasionally (e.g., low hematocrit) Blood, albumin routinely

Systemic perfusion pressure

50-80 mm Hg

Influence of alpha stat versus pH stat Minimal (at moderate hypothermia) Glucose regulation Hypoglycemia

Hyperglycemia

20-50 mm Hg Marked (at deep hypothermia)

Rare

Common

Frequent

Less common

See Table Parameter

Score <3cm

1

>6cm

3

Maximum diameter 3-6 cm

Location Venous drainage

2

Noneloquent cortex 0 Eloquent cortex*

1

Superficial

0

Deep

1

* Eloquent site: Sensorimotor, language, or visual cortex; hypothalamus or thalamic nuclei; internal capsule; brainstem.

Cerebral physiological values Global CMRO2

3-3.5 mLO2/100g/min

Brain weight

2% of total body weight

CBF

45-55 ml/100 g/min

% of CO to brain

∼12-15%

% of total body oxygen consumption ∼20%

Perioperative medications Medication

Effect on CMRO2

Barbiturates

Decrease

Propofol

Decrease

Etomidate

Decrease

Ketamine

Increase

Benzodiazepines

Decrease

Lidocaine

Decrease

Narcotics

No effect/unknown

Epinephrine and norepinephrine

Increase

Dobutamine

Increase

Beta-blockers

No effect

Dexmedetomidine

No effect

Nondepolarizing muscle relaxants No effect Depolarizing muscle relaxants

No effect

Volatile agents

Decrease

Nitrous oxide

Increase

Table 1 Composition of CSF: Plasma CSF Plasma pH

7.31 7.41

Dsmolality (mOsm/kg H2O) 289 289 Na+ (mEq/L)

141 140

K+ (mEq/L)

2.9 4.6

Ca+ (mEq/L)

2.5 5.0

Mg+ (mEq/L)

2.4 1.7

Cl- (mEq/L)

124 101

HCO3- (mEq/L)

21

23

Glucose (mg/100 mL)

61

92

Protein (mg/100 mL)

28

7000

See Table FFP Cryoprecipitate Fibrinogen Dose

8 U

2 U

Volume (mL)

2,000 400

4g 200

Δ Fibrinogen (mg/dL) 100

130

120

Δ Hct(%)

-3

-1.5

-11

Classifications Mild pH

Moderate

7.25-7.3 7.0-7.25

Severe <7.0

HCO3 (mEq/L) 15-18

10-15

Mental status

Alert/Drowsy Stupor/Coma

Alert

<10

See Table Normal value (mean) EDV 120 mL ESV 45 mL SV

75 mL

EF

55-70%

Table 1 Summary of EEG Frequencies at Different States of Anesthesia Depth of

EEG Frequency

Anesthesia

Classical Frequency

EEG

Morphology

Bispectral Index (BIS)

Awake

Fast, low amplitude

β, α very fast γ, β2

High 90's

Sedation

Slow, increased amplitude

More β less α

Low Ws to 80's

Increased slowing, appearance of

Appearance of α spindles

Light GA GA Deep GA

slow waves

Increased slowing, prominent slow waves

Mostly slow waves

Burst suppression Varying suppression with bursts

GA = General Anestnesia

and θ

70'sto 60's

Mostly θ and δ

40 to 60

Mostly δ

20 to 40

Suppression, δ

Teens to single dinks

Table 1 Effect of certain agents or conditions on EMG monitoring Agent Volatile Anesthetics Barbiturates Etomidate

Effect on evoked potential Depression of amplitude Prolongation of latency Depression amplitude

Prolongation of latency Low dose: increase amplitude, prolongs latency

High dose: reduces amplitude, prolongs latency

Ketamine

No effect or may increase amplitude

Narcotics

Mild reduction of amplitude

Benzodiazepines Local Anesthetics Neuromuscular Blockade

Local or Systemic Hypothermia

Decrease amplitude

Little effect on latency Alters muscle action potential Abolishes spontaneous and triggered EMG Neurotonic stimulation of EMG activity

Tissue Compression or Retraction Affects EMG amplitudes or latency

See Table % of TBW Liters (80 kg male) % of total body water Total body water

60%

48 L

100%

Intracellular fluid

40%

32 L

66%

Extracellular fluid 20%

16 L

33%

Interstitial space

12 L

24%

4 L

10%

15%

Intravascular space 5%

See Table Electrolyte Plasma (mEq/L) Interstitial space (mEq/L) Intra-cellular space (mEq/L) Na+

142

145

10

K+

4

4

160

Cl-

101

114

3

HCO3-

27

31

10

Ca++

5

5

2

Mg++

2

2

26

pH

2

2

100

Protein

16

1

65

See Table FFP Purified fibrinogen Dose

8 U

4 g

Volume(mL)

2,000 200

Δ Fibrinogen (g/L) 1.0

1.2

Δ Hct(%)

-1.5

-11

See Table Patients blood type Compatible FFP type A

A or AB

B

B or AB

AB

AB

O

O, A, B, AB

Physiological changes with aging Organ System Neurologic

Cardiac

Parameter

Change

Cerebral blood flow

Decrease

Cerebral blood volume

Decrease

Shcrt-term memory

Decrease

Temperature regulation

Decrease

Systolic blood pressure

Increase

Diastole blood pressure

Increase

Pulse pressure

Increase

Resting bean rate

Decrease

LVEDV

Increase

LVESV

Increase

Stroke volume

Increase

Cardiac output

No change

Maximal oxygen consumption Decrease

Pulmonary

Hepatic

Barorewflraes

Decrease

PaO2, O2 saturation

Decease

PaCO2

No change

Total lung capacity

No change

Residual volume

Increase

Vtial capacity

Decrease

Functional residual capacity

Decrease

Closing volume

Decrease

FEV1

Decrease

FVC

Decrease

Ciliary function

Decease

Respiratory muscle strengh

Decease

Mass

Decease

Blood flow

Decease

Drug metabolism

Decease

Gstrointestinal Esophageal function

Decease

Gastric motility

Decrease

Acid secretions

Decrease

Absorption

Decrease

Renal

Mass

Decease

Blood flow

Decease

Creatinine dearance

Decrease

Glomerular filtration rate

Decrease

Electrolyes

No change

Musculosletal Muscle mass

Decease

Bone mineral density

Decease

Body fat

Increase

Total body water

Decease

See Table I:E ratio I-time (s) RR 10 E-time (s) RR 10 I-time (s) for RR 6 E-time (s) for RR 6 1:4

1.2

4.8

2

8

1:3

1.5

4.5

2.5

7.5

1:2.5

1.7

4.3

2.8

7.2

1:2

2

4

3.3

6.6

1:1.5

2.4

3.6

4

6

1:1

3

3

5

5

1.5:1

3.6

2.4

6

4

RR = 10 correlates to 6 seconds/breath 6 is divided by the l-time plus the E-time (6/[l-time + E-time]). For example, for an l:E ratio of 1:4,6/(1 + 4) = 6/5 = 1.2 seconds. This value is multiplied by the ratio value; for example 1.2 x 1 = 1.2 seconds for the l-time and 1.2 x 4 = 4.8 seconds for the E-time. Note: the l-time plus the E-time should equal 5 seconds.

See Table Degree of tissue trauma

Fluid replacement

Minimal trauma (hernia repair, laparoscopic procedures) 2-4 mL/kg/hour Moderate trauma (cholecystectomy)

4-6 mL/kg/hour

Severe trauma (bowel resection, Whipple)

6-8 mL/kg/hour

See Table below Pneumoperitoneum

Pneumoperitoneum + Trendelenburg

Pneumoperitoneum +

Reverse Trendelenburg

Cardiac Preload

Decreased

Afterload

Increased

Cardiac output Heart rate Rhythm MAP

Increased

Decreased initially (secondary to decreased Increased (secondary preload)

to increased preload)

Deceased (pools in lower extremities)

Deceased (secondary to decreased preload)

Increased if hypovolemic or sympathetic response to hypercarbia

Arrhythmia may occur from sympathetic response or pH Vagal reflex or asystole Increased

Increased

Decreased

residual

Decreased

Decreased

Increased

Compliance

Decreased

Decreased

Increased

inspiratory

Increased

Increased

Decreased

PaO2

Decreased

Decreased

Increased

PaCO2

Increased

pH

Decreased

GFR

Decreased

Decreased

Increased

Urine output

Decreased

Decreased

Increased

Pulmonary Functional capacity Peak

pressure

Renal

Table 1 Relevant Child-Pugh Scores Feature

0 Points 1 Point 2 Points

Albumin

>3.5

2.8-3.5 <2.8

Bilirubin

<2

2-3

>3

PT elevation

<4s

4-6s

>6s

Ascites

None

Treated Refractory

Encephalopathy None

Treated Refractory

See Table Agent

MAC Value

Desflurane

6%

Sevoflurane

2%

Isoflurane

1.15%

Nitrous oxide 104%

Table 1 Cardiovascular variables according to age (1) Age 0-6 mos

Respiratory rate (per minute) Heart rate (per minute) SBP (mm Hg) 30-50

120-140

65

6-12 mos 20-40

95-120

85-90

1-5 yrs

20-30

90-100

95

6-10 yrs 18-25

80-100

95

>10 yrs 12-25

60-100

120

Table 1 Age-Related Pulmonary Physiology Age related pulmonary physiology Newborn Infant Small child School age Weight (kg)

2.5-5

5-10

Resp. Rate (breaths/min)

40-60

30-60 30-40

12-20

Tidal Volume (mL/kg)

8-10

8-10

8-10

8-10

O2 Consumption (mL/kg/min)

9

7

6

3.5

Functional Reserve Capacity (ml/kg) 10

15

30

30

Resistance (cm H2O/L/sec)

30

20

1-2

40

10-20

>20

Table 2 Age-Related Airway Sizes Age reiaiea airway sizes Age (years) ETT size (mm) LMA size DLT (Fr) Trachea (mm) <1

3.5-4.0

1-1.5

―

<5

M

4.0-5.0

1.5-2

―

5-7.5

4-6

5.0-5.5

2-2.5

―

8

6-8

5.5-6.0

2.5

―

9

8-10

6.0 cuffed

2.5-3

26

9-10.5

10-12

6.5 cuffed

3-4

26-28

10-12

See Table Temp corrected Total CO2 Content PH PCO2 pH Stat

yes

Mpha stat no

↑

-

-

-

↑

↑

See Table Minimum level (μL)

Relevant conditions

10,000-20,000

All patients to prevent spontaneous bleeding

20,000

Gl endoscopy; LP

50,000

Liver biopsy, procedures with insignificant blood loss, vaginal delivery

20-50,000

DIC, fiber-optic bronchoscopy in a BM transplant

50,000

Active hemorrhage. Major surgery in leukemia, invasive procedure in cirrhosis

50-60,000

Cardiopulmonary bypass

100,000

CNS procedures

Multifactorial Risk Index for Predicting Postoperative Respiratory Failure Type of surgery AAA repair

27

Thoracic

21

Neurosurgery, upper abdominal or peripheral vascular 14 Neck

11

Emergency surgery

11

Albumin(<30 mg/dL)

9

BUN(>30 mg/dL)

8

Partially or fully dependent functional status

7

H/O of COPD Age (years)

6

>70

6

60-69

4

See Table Left shift (↑ affinity)*

Right shift (↓ affinity)*

↓[H+] (↑pH)

↑[H+] (↓pH)

↓2,3-DPG

↑2,3-DPG

↑ temperature

↓ temperature

Fetal hemoglobin (HbF); P50= 19 mm Hg Pregnancy; P50 = 31 mm Hg Dyshemoglobins (MetHb, COHb)

Hemoglobinopathies (thalassemia, sickle cell hemoglobin), SulfHb

Tobacco use

Chronic anemia Volatile anesthetics

* ↑ Affinity of Hgb for O2 → holds tightly to O2; ↓Affinity of Hqb for O2 → released at the tissue level.

Table 1 Medications that affect the QT interval Strong Association Droperidd, Methadone, Amiodarone,

Procainamide, Quinidine, Sotald, Disopyramide, Chlotoquine, Clarithromycin, Erythromycin, Pentamidine, Chloipiomazine, Halopericbl, Thioridazine, Cisapride, Ctomperidone, Organophosphates, Ibutilide, Probucol, Sparfloxadn, Pimozide, Halofantrine, Levomethadyl, Mesoridazine Moderate Association Dolasetron, Granisetron, Ondansetron, Oxytocin, Chloral hydrate, Salmeterol, Octreotide, Tacrolimus, Flecainide, Nicardipine,

Azithromycin, Gatifloxadn, Levofloxadn,

Moxifloxadn, lithium, Quetiapine, Risperidone, Venlafaxine.Ziprasidone, Amantadine,

Tamoxifen, Voriconazole, AlfuzosinAtazanavir, Clozapine, Vardenafil

Inaeased risk for Congenital LQTS patients Amitiiptyline, Ciprofloxacin, Citalopram,

Clomipramine, Desipramine, Diphenhydramine,

Doxepin. Fluconazole, Fluoxetine, Galantamine, Imipramine, Itraconazole, Ketoconazole, Mexiletine, Nortriptyline, Paroxetine,

Ftotriptyline, Ritonavir, Sertraline, Solitenacin,

Trazodone, Trimethoprim-Sulfa, Trimipramine,

Dobutamine, Dopamine, Ephedrine, Epinephrine, Isoproterenol, Norepinephrine, Albuterol,

Cocaine, Ketamine, Phenteramine, Ritodrine, Succinvl choline. Pancuronium

See Table Organs Gonads

Tissue weighting factors 0.2

Bone marrow 0.12 Lung

0.12

Stomach

0.12

Bladder

0.05

Chest

0.05

Liver

0.05

Thyroid gland 0.05 Esophagus

0.05

Skin

0.01

Bone surface

0.01

Remainder

0.05

Table 1 Urinary diagnostic indices Index

Pre-renal ATN

U/P osmolality

<1.5

1-1.5

Urine Na+ (mmol/L)

<10

>40

Fractional excretion of sodium FENA <1%

>1%

Renal failure index

<1

>2

BUN/Cr ratio

>20

<10

See Table Monitor

Sensitivity (ml/kg)

TEE

0.02

Precordial Doppler

0.05

PA catheter

0.25

Transcranial Doppler High ETN2

0.5

ETCO2

0.5

O2 saturation

Low

Direct visualization

Low

EKG

1.25

Commonly used anesthetic drugs* Drug

Vd (L/kg) Loading close In obese patients Maintenance dosi In obese patients

Thiopental

2.2-3.2

Reduced

NA

Methohexital

12

TBW

TBW

Ptopofd

3.1-6.2** IBW

TBW

Etomidate

2.5-4.5

TBW

TBW

Ketamine

2-3.5

TBW

TBW

Midazolam

1-2.5

TBW

IBW

Diazepam

0.7-3.4

TBW

IBW

Lorazepam

0.8-1.3

TBW

IBW

Fentanyl

6

TBW

TBW

Sufentanil

1.7-2.9

TBW

IBW

Remlfentanll

0.1-0.35

IBW

IBW

Hydtomorphone 2.9

NA

NA

Morphine

1-4.7

NA

NA

Sucdnylchdine

0.04

TBW

NA

Pancuronium

0.26

IBW

IBW

Vecuronium

0.2

IBW

IBW

Rocuronlum

0.21-0.27 IBW

Reduced

Clsatracurium

0.15

TBW

TBW

Atracurium

0.1-0.39

TBW

TBW

*Average value tor adult patients. **Increases with duration of use (∼ 60 L/kg with continuous infusion for 1 week). TBW = Total Kdv webht: IBW = Ideal botfv weioltt.

Table 1 Angiotensin converting enzyme inhibitors Drug Enalapril

(Vasotec®)

Captopril

Dose IV 0.625-5 mg q6h; pediatric 5-

10mcg/kq/dose PO 15-5 mgrtfay-BID

(up to 20 mg ACEL); pediatric 0.08-0.1 mg/kg/close

PO 2.5-5 mg/day-BID(upto 20 mg BID);

Onset Duration IV 5-

15min PO

1hr

Ramipril

(Altace®) Quinapril

(Accupril®) Lisinopril

(PrinMl®, Zestril®)

Benazepril

PO 1.25-20 mg/day (maximum)

0.07mg/Kg/day

PO 10-80 mg/day; pediatric 0.2

(Lotensin®) mg/kg/day

Fosinopril

(Monopril®)

1-2 hrs

PO 5-40 mg/day; pediatric 5-10 mg/day 1hr

PO 5-40 mg/day; pediatric

PO 10-40 mg/day; pediatric 5-10

mg/day (decrease dose in hepatic dysfunction)

IV 6 hrs

Esterase conversion to

hrs

excretion, sane fecal

PO 12-24 active drug, 60-80% renal

1-1.5 Half life

(Capoten®) pediatric 0.5 mg/kg/dose 2-4 times daily hrs

1hr

1-2 hrs

Metabolism

1-2 hrs

24 hrs

24 hrs

24 hrs

24 hrs

24 hrs

Only ACEl available

IV. Dose adjustment requi reef for renal disease

Hepatic-50% metabdizect

Shortest T 1/2 of

kidney

incidence of cough

50% exaeted unchanged by ACEIs Highest Esterase conversion to

active drug excreted 60% urine

Some fecal excretion

Esterase conversion to active drug, 50-60% excreted in urine

None. Excreted unchanged in urine

Esterase conversion to

active drug. Mostly hepatic metabolism/nonrenal

Esterase conversion to 1hr

Comments

active drug. Hepatobiliary

Not a prodrug

Total daily doses

may be given BID Only ACEl not

requiring dose

excretion. Some metabdites adjustment farenal via urine.

dysfunction

Table 2 Angiotensin receptor blockers Drug Candesartan (Atacand®)

Eprosartan (Teveten®)

Irbesartan (Avapro®)

Dose

PO 4-32 mg/day

PO 600 mg/day or 400-800 mg/day or BID.

PO 150-300 mq/day (75 mg/day if

volume depleted); pediatric 75-150 mg/day

Telmlsartan(Micardis®) PO 40 mg/day (up to 80 mg/day)

Onset Duration Metabolism/exaetton 2-3 hrs

1-2 hrs

1-2 hrs

1-2 hrs

Exceeds 24 hrs

Exceeds 24 hrs

Exceeds 24 hrs

Up to 24 hrs

mg/day CHF: 20-40 mg BID. titrated up to 320 mg/day;

2 hrs 24 hrs

pediatric 1.3 mg/kg/day

Losartan (Cozaar®)

Dlmesartan (Benicar®)

form. Most clearance renal

to-severe hepatic disease

Nodose reduction

fecal excretion

hepatic/renal disease

metabolism, >90%

required for

Hepatic via

Nodose adjustment

excretion

disease

CYP2C9,80% fecal

needed for renal

Hepatic via

20 mg/day starting

excretion

hepatic disease

conjugation 97% fecal dose in elderly a

Hepatic to inactive

metabolite, 83% fecal excretion

hepatic disease. No dose adjustment needed in

elderly/renal dysfunction

Hepatic to more

0.7 mg/kg/day

CYP 2C9 and 3A4

with diuretic 25 mg/day; pediatric 6 hrs 24 hrs

pediatric 10-20 mg/day

needed in modsrate-

Minimal hepatic

PO 50-100 mg/day. Initial dose

PO 20 mg/day up to 40 mg/day;

Dose reduction

Caution In severe

PO HTN:80-60 mg/day up to 320 Valsartan (Diovan®)

Small bowel to active

Comments

1-2 hrs

24 hrs

potent metabolite via

Hydrolyzed to active

form in Gl tract renal and fecal excretion

Initial dose 25 mg with hepatic

dysfunction, no

change in elderly a renal disease

No dosage change needed for

hepatic/renal/elderly patients

Table 1 Class IA antiarrhythmics Drug

Dose PO as sulfate 100-600

Quinidine

mg q4-6h

As gluconate 324-972 mg q8-12h

Onset Sulfate

time to

peak 2 hr

Gluconate 3-5 hr

Duration

Metabolism

Half-life 6-8 hr

Hepatic via several

Increases risk of digoxln

elderly,

metabolites, some excretion

neuromuscular blocking

(prolonged in

cytochromes to Inactive

cirrhotics, CHF) In urine unchanged

IV loading dose 20-50 mg/tnln up to

(Pronestyl®)

infusion 1-4 mg/min. May be given IM

Pediatric-load 3-6

10-30min lM

mg/kg/dose up to 15

Half-life parent 2.5-4.7 hr.

NAPA 6-8 hr

mgAg total, then 20-80

metabolite (NAPA) 80% of which excreted unchanged

ql2h. Pediatric vary by

active

in urine 50% of parent drug metabolite (NAPA).

excreted in urine unchanged. Genetic variation In

Hepatic, via CYP3A4 to

q6h or 200 mg q12h q6h or 300 mg

high doses; has an

acetylatlon rates

<50 kg wt: PO 100 mg

(Norpace®)

agents

Hepatic acetylatlon to active given rapidly or

mcg kg/min

Disopyramide >50kgwt.: PO 150 mg

toxicity, potentiates

*Hypotension when

17 mg/kg*, then Procainamide

Comments

0.5-3.5 hr

Half-life 1.5-8.5 Inactive metabolites, 40-60% hr

age

*Unless hypotension ensues ot QRS widens by 50%

excreted unchanged Into urine

Reduces cardiac output significantly (10%),

may aggravate CHF; prominent

anticholinergic effects

Table 2 Class IC antiarrhythmic agents Drug

Flecainide

(Tambocor®)

Dose PO 50-150 mgq12h.

Pediatric: 3-6 mg/kg/day in 3 divided doses

PO-IR form: 150mg q8h Propafenone (Rythmol®)

up to 300mg q8h ER form: 225-425 mg q12h. Pregnancy risk C,

cauticnwith breastfeeding

Onset Time to

peak

1.5-3 hr

Duration

Dose alteration required in

CHF;renal

in hepatic disease. Pregnancy

prdonged in

inactive products,

failure

50% unchanged

Time metabolizers peak

Comments

Half-life 7-22 hr Hepatic via 2D6,to

Extensive

to

Metabolism/Excretion

half-life 2-10 hr. Poet

3.5 hr metabolizers

half-life 10-32 hr

IR= immediate release; ER = extended release

excreted in urine, 10-

renal disease Action pdonged risk C enters breast milk

Hepatic, via CYP2D6

Dose reduction required in

Pharmacogenomic

2nd/3rd degree blocks, or

(major) and 3A4. variation exists,

hepatic disease, patients with widened QRS. Pregnancy risk

requires dose alteration C, caution with breastfeeding

Table 1 Selective serotonin reuptake inhibitors Drag

Dose FO 20-40

Citalopram (Celexa®)

mg 0D

Pediatric 10-20

mg/day Esdtalopram (Lexapro®)

Fluoxetine (Prozac®)

Onset Within 1 effect 8-

12 weeks

mg QD, all As above ages >12

Hepaticvia CYP3A4 and

hours

Half-life 27-32 hours

Half-life parent

PO 10-20 pediatric 5-

(Paxil®)

pediatric 10-

metabolite

12 days

(Zoloft®)

Age >

6:25-50

nig/day

CYP2C19 to active

Hepatic via CYP2D6, to As above

Half-life 21 hours

minimally active metabolites, 2/3

excreted inuring 1/3 fecal

PO 50-200 Sertraline

Similar to citalopram

metabolite 9-

20mg/day mg QD,

urinary excretion

Hepatic via CYP2D6 and

PO Paroxetine

active metabolites, some

drug up to 6

As above days,

20 mgrtlay

20mgQD,

Metabolism/excretion

week, full Half-life 24-48 CYP2C19 to minimally

PO 10-20

mgQD,

Duration

Half-life parent Hepatic via CYP2C19 As above

drug 26 hairs, and CYP2D6 to active metabolite 66 hairs

metabolite, excreted in both urine and feces

Comments Lower dose in severe renal failure. Less

potential fa drug interactions. Pregnancy risk C, excreted In breast milk

As above

Less likely to produce withdrawal syndrome. Many drug interactions. Lower ctose in

hepatic disease/elderly Pregnancy risk C, breastfeeding not recommended Lower doses in hepatic/renal

disease/elderly. Many drug interactions.

Anticholinergic side effects. Pregnancy risk D, enters breast mill; caution

Less potential fa drug interactions. Lower

ctose in hepatic disease/elderly. Pregnancy risk C enters breast milk, caution

Table 2 Serotonin norepinephrine reuptake inhibitors Drug

Dose

Onset

PO 25-75

Within 1

Venlafaxine mgTID or XR week, full (Effexor®)

Duloxetine

(Cymbalta®)

37.5-225 mg OD

PO 20-60

effect 8-

12 weeks

mgOD/dMded As above BID

Duration

Metabolism/excretion

Half-life

parent drug 3- Hepatic via C YP2D6 to 7 hours,

metabolite 913 hairs

Half-life 12 hours

active metabolites,

excreted in urine (90%) Hepatic via CYP2D6 and CYP1A2 to Inactive

metabolites, 70% excreted in urine, 20% in feces

Comments Lower dose in hepatic/renal

disease/elderly Active metabolite is

desvenlafaxlne (Pristia®). Pregnancy

risk C, breastfeeding not recommended Lower doses in renal/hepatic disease. Pregnancy risk C, breastfeeding not recommended

Table 3 Tricyclic antidepressants Drug Ami til plyline

(Elavil®)

Dose PO 25-150

mg/day once or

divided. Pediatric 0.1-2 mg/kg/day

Onset 4-6 weeks for depression,

analgesia 1-3

(Napamin®)

mg/day once or divided, age >6:1-3

1-3 weeks

PO 50-150

(Pamelor®) divided. Pediatric 1-3 mg/kg/day

9-27

weeks

mg/kg/day

Nortriptyline mg/day once or

Half-life

weeks, migraine 6 hours

PO 75-150 Desipramine

Duration Metabolism/excretion

1-3 weeks

Hepaticvia CYP2D6 and others to active metabolite

(natriptyline), excreted in urine/feces

Half-life

HepaticviaCYP2D6to

hours

excreted in the urine

7-60

Half-life 28-31 hours

metabolites, 70%

HepaticviaCYP2D6and others to Inactive

metabolites that are

excreted mostly in the urine

Comments Lower cbse in hepatic disease.

Avoid use in elderly Pregnancy risk C, breastfeeding not recommended

Lower cbse in elderly. Pregnancy risk unknown, enters breast milk

Lower doses in hepatic

disease/elderly, better tolerated

than others in elderly Pregnancy risk unknown enters breast milt:

Table 4 MAO inhibitors Drug Isocarboxazid

Phenelzine

Dose PO 30-40 mg BID

PO 30 mg BID

rranylcyprcmine PO 20-30 mg BID

Selegiline

Rasagiline

(Azilect®)

Onset Unknown Therapeutic effect 2-4 weeks

Peak 3-6 weeks

Metabolism/excretion Unknown

Half-life 12 Oxidized by MAO, metabolites hours

Therapeutic

Inhibits

3 weeks

10 days

excreted in urine

effect 2 days to MAO up to Excreted in urine

PO 5 mg BID

Topical patch 6-12 Oral 1 hour mg/24 hours PO 1 mg QD

Duration

Oral 1 hour

Oral 24-72 hours

1 week

Comments Nonspecific MAO inhibitor

Nonspecific MAO inhibitor

Nonspecific MAO inhibitor

Hepatic via CYP2B6 to active and Selectively inhibits inactive metabolites excreted

MAO-B, used in

Hepaticvia CYP1A2 to inactive

Selectively inhibits

urine

Parkinson disease

mostly in urine

metabolites, excreted mostly in

Parkinson disease MAO-B, used in

Table 1 Long-acting beta-agonists Drug

Salmeterd

(Serevent®)

Famoterol

(Foradil®)

Dose

Onset

SO meg BID inhaler (adult Asthma30min, and pediatric > age 4)

COPD 2hr

12 meg BID Inhaler, 20

80% peak effea

and pediatric age >5)

for nebulizer

Duration Metabolism/excretion Hepatic via CYP3A4, 12 hr

metabolites are

excreted in the urine and feces

Hepatic via several

meg BID nebulizer (adult in 12 min, 2 hr 10-12 hr

CYP isoenzymes,

enantiomerof formoterol

IS meg BID nebulizer

Peak effect 1-3 hr

Half-life 26 hr

steroids/dose Fluticasone (Advaif®) 1-2 inhalations/day

Bu desonide (Sym

bicort®) Mometasone

metabdites excreted In (Dulera®) both 2 urine inhalations BID

Arformoterol

(Brovana®)- R-

Combos with

Hepatic via CYP2D6 and CYP2C19

Indicated only In COPD patients No steroid combos available

Table 1 Beta blocking agents Drug Non-selective Propanold

(Inderal®)

Dose IV 1-3 mg PO 40-320 mg divided doses Pediatric

W 0.01-0.1 mg/kg/dose

Selective β1>β2

vietoprolol

(Lopressor®

IV 1-15 mg PO 50-200 mg Pediatric: 1-2 mgrtcg/day

Toprol®) Atenolol

(Tenamin®)

IV 5-10 mg PO 50-200 mg Pediatric: 0.5-1.5 mg/kg/day

Onset IV

minutes PO 1-2 hr

IV peak 20 min

PO 1.54 hr

(Brevibloc®)

50-150 mcg/kg/min Pediatric 100-500

mcg/kg then 50-250

peak

effect

min

IV 20 mg, up to 40-80

IV 2-5

activity

dose 300 mg Pediatric

20min

(Trandate®)

Carvedilol (Coreg®)

0.3-1 mg/kg/dose

PO 3.125-6.25 mg BID, max 25 mg/day

1A3 to active and

(IR)

IV 5-8 hr PO 10-20 hr(IR) 24 hr(SR)

PO 12-24hr

that are excreted in the urine

Hepatic, extensive via 2D6 to inactive

metabolites excreted in urine

Limited hepatic,

excreted feces and

dose long duration

PO 1-2 hr

Start with low doses in

elderly/severe hepatic disease

Pregnancy risk C, caution with breastfeeding

Reduce dose in elderly/hepatic disease Pregnancy risk Q

caution with breastfeeding

Reduce dose in severe renal disease. Pregnancy risk D,

metabolites excreted in urine

Titrate to response, used for intraoperative

HTN/tachydysrhythmia.

Pregnancy risk C, breastfeeding unknown

IV 2-18 hr (dose-

min PO dependent) to 2hr

Comments

urine (40% unchanged) caution with breastfeeding

IV 2-10 longer if high esterases to inactive

with α1

Labetalol

Hepatic via 206 and

IV 10-30 min, Rapid via RBC

Non-selective, mg every 10 min, max

Metabolism/excretion

(SR), 6-12 hr inactive metabolites

2-4 hr

mcg/kg/min

blocking

PO 24-27 hr

PO

IV 10-80 mg bolus, then Esmolol

Duration

P08-12hr (dose-

Hepatic conjugation,

May need dose reduction in

urine

C, cauticn with breastfeeding

mostly excreted in

hepatic disease. Pregnancy risk

dependent) Extensive via hepatic T 1/2 7-10 hr

cytochromes to 3

active metabolites that are excreted fecal ly

Lower dose range used in chronic CHF and elderly.

Ccntraindkated in severe liver disease. Pregnancy risk c, breastfeeding unknown

Table 1 Dihydropyridine calcium channel blockers Drug

Dose

Onset

Duration Metabolism/excretion Hepatic, 90% to

PO 2.5-10 mg QD Time to

Amlodipine(Norvasc®) Pediatric age >6: peak 6-12 24 hr 2.5-5 mg QD

hr

Felodipine (Plendil®)

Pediatric 2.5 mg

Hepatic, 70% to 2-5 hr

24 hr

OD

Nifedipine

QD,upto 120-180

(Procardia®, Adalat®) mg/day Pediatric 0.25-0.5

Elimination 20 min

immediate release

mg/kg/day

Nicardipine

(Cardene®)

by 2.5 mg/hr

every 5-15 min

up to 15 mg/hr

Nimodipine

(Nimotop®)

Clevidipinet

(Cleviprex®)

21 days, started within 96 hr of SAH

hr (7 hr in elderly or In

IV <8 h(

IV 10 min PO

PO 30min sustained to 2hr

PO 30-60 mg BID PO 60 mg q4h for

T-1/2 2-5

cirrhotics)

IV Infusicn 5

mg/ht increased

release 812 hr

Time to

peak 1 hr

T-1/2

serum 1-2 hr

mg/hr titrated to

urine. Major substrate

Hepatic to inactive

metabolites, mostly excreted via urine.

Major substrate for CYP3A4

4-6 mg/hr

IR = immediate release. ER = extended release

renal disease. Pregnancy risk C, breastfeeding not recommended

Lower ctose range in hepatic

disease/elderly. No change in breastfeeding not recommended

Lower ctoses should be

considered in hepatic disease

or elderly. No change in renal disease. Pregnancy risk C, breastfeeding not recommended

May reduce dose to 3 mg/hr

inactive metabolites

at lower dose range fa

CYP enzymes to

excreted both in urine and feces Major

substrate for CYP3A4 metabolism,

metabolites excreted

both urine and feces. Maja substrate for

Rapid hydrolysis by 5-15 min

disease/elderly. No change in

Hepatic via several

CYP3A4

2-4 min

Lower ctose range in hepatic

that are excreted in the renal disease. Pregnancy risk C,

Extensive hepatic

IV infusicnfor

HTN-initial 1-2

inactive metabolites

for CYP3A4

PO(IR)10-20mg

TIDER 30-60mg

Major substrate for CYP3A4

PO 2.5-10 mg QD, up to 20 mg QD

inactive metabolites.

Comments

serum and tissue

esterases to inactive

after response achieved. Start elderly/patients with hepatic or renal disease. Pregnancy risk C, enters breast milk

Reduce dose to 30 mg q4h in hepatic disease- May not be used IV. Pregnancy risk C, breastfeeding not recommended

Therapy limited to 1,000 mL of suspension/day due to lipid load Start at lower dose In elderly. No change in

metabolites excreted in renal/hepatic disease. Rebound urine and feces

hypertensicn a risk. Pregnancy risk Centers breast milk

Table 2 Non-dihydropyridine calcium channel blockers Drug Verapamil (Calan®

Isoptin®)

Dose IV for SVT 2.5-5 mg initial, then 5-10 mg in 15-30 min

(Cardizem®)

IV 1-5 min

Pediatric: a 1-03 mg/kg/dose PO 1PO 80 mg(IR)TID or 120-480 2 hr mg/day(SR)in 1-2 doses

IV for SV dysrhythmia 0,25 Dlltiazem

Onset Duration Metabolism/excretion

rngftg bolus then 10 mg/hr

infusion (up to 15 mg/hr) PO

180-240 mg(SRJ/QD max 480 mg/day

(IR)

IV 3 min

PO(IR tab)

30-60 min

IV 10-20 Hepatic via several min PO

CYP enzymes, to active

(IR)

accumulate

6-8 hr

IV bolus 1-3 ht

infusion

after DC

0.5-10 hr

IR = immediate release SR = sustained release

metabolites which can

Comments Active metabolites have 20% of the activity of verapamil. Cose

reduction is needed in hepatic/renal insufficiency. Pregnancy risk Q

treastfeeding not recommended

Hepatic via several

Consider lower doses in the elderly.

active metabolites

disease, however, close monitoring

CYP enzymes, some which accumulate,

excreted in urine and feces

No changes in renal/hepatic

should be performed. Pregnancy risk C treastfeeding not recommended

Table 1 Drug Spironolactone (Aldactone®)

Dose PO 12.5-25 mg QD

or BID Pediatric 1-3 mg/kg/day

Eplerenone (lnspra®) PO 25-50 mg QD

Triamterene

(Dyrenium®)

PO 100-300 mg/day Pediatric-1-4 mg/kg/day

PO 5-20 mg/day

Amiloride(Midamor®) Pediatric 0.4-0.625 mg/kg rtlay

Onset Tlmetopeak34hr

Diratlon Metabolism/excretion Hepatic, to active

2-3 days metabolites, excreted in urine and feces

Time to peak Half life 1.5 hr

2-4 hr

4-6 hr

7-9 hr

Comments May also be combined with HCTZ. Pregnancy risk C, breastfeeding not recommended

Hepatic via CYP3A4 to Many drug interactions. inactive metabdites,

Pregnancy risk B,

excreted In urine, feces breastfeeding unknown Metabolized to sulfate conjugate, excreted in uhne

Dyazide®, Maxzide®

combos with HCTZ. Pregnancy risk C,

breastfeeding unknown Usually combined with HCTZ

2 hr

24 hr

Excreted in urine and feces unchanged

(Moduretic®). Pregnancy risk B, breastfeeding unknown

Table 1 HMG CoA reductase Drag

Aorvastatin (Lipitor®)

Dose PO 10-80 mg/day

Pediatric 10

mg/day

Pediatric 1020 mg/day

Lovastatin

(Mevacor®) Pravastatin

(Pravachol®)

Rosuvastatin (Crestor®)

Simvastatin (Zocor®)

PO 20-80 mg/day

PO 40-80 mg/day

3-5 days

PO 10-40 mg/day

Pediatric 520 mg/day PO 20-40 mg/day

Pediatric 10 mg/day

14 ht active metabolites 20-30 hr

Peak

within 4 weeks

3 days

half-life 3-9 hr

1.1-17hr

Several days, 4

Pediatric 20- weeks fa 40 mg/day

Duration Parent drug

mg/day

PO 20-80 Fluvastatin(Lescol®)

Onset

week

3 days,

2 weeks

Hepatic via CYP3A4, to active with other and inactive metabolites, excreted in bile

CYP3A4substiates,

Contraindicated in liver disease

Hepatic via CYP2C9, other

cytochromes, to active and inactive metabolites, 90%

Reduce dose In renal disease

excreted In feces

Hepatic via CYP3A4 to active metabdite, excreted in feces

half-life 77 hr active metabdite, excreted

mostly in feces, <20% renal

Fecal exaction, 90%

half-life 19 hr unchanged, 10%

peak effect Unknown

Comments Fewer problems when given

Hepatic/non-cytochrome, to

peak effect

Up to 1

Metabolism/excretion

metabolizedvia CYP2C9

Active component in red yeast rice

Initial dose 10 mg/day in hepatic and renal disease

Cent vindicated in hepatic disease. Lower ctose in

severe renal disease. Lower dose in Asians

Recent decrease in max dose

Hepatic via CYP5A4, excreted due to myopathy risk. Dose 5 mostly in feces, some urine

mg/day in severe renal failure

Table 1 Insulin pharmacokinetics Insulin Preparation

Trade Name

Onset (hours) Peak (hours) Duration (dose-dependent)

Very rapid/rapid

(hours)

Llspro

Humalog®

Aspart

Novalog®

Glulisine

Apidra®

Regular

Humulin R®

Intermediate

Novolin R®

NPH

0.25-0.5

0.5-1.5

4-6

1.6-2.8

3-4

2-3

6-8

Humulin N®, Novdin N 1

4-8

10-14

Glargine

Lantus®

1.5

None

24-30

Detemir

Levemir®

3-4

3-9

20-23

0.5-1

Long-acting

Source: Tabfe adapted from Stoeltina Hillier Pharnidrolcay and Physiology in Anesthetic Practicei 4th Ed.

Table 1 Orally administered alpha antagonists Agent

Trade name

Dose

Indications

Prazosin

Minipres®

0.5-40 mg BID

HTN, BPH (non labeled use)

Terazosin

Hytrin®

1-20 mgcnce daily

BPH (most common), HTN

Doxazosin Cardura®

1-16 mgcnce daily

BPH (most common), HTN

Tamsulosin Flomax®

0.4-0.8 mg once daily BPH, not indicated for HTN/no effect on BP

Alfuzosin

10 mg once daily

Uroxatral

BPH, not indicated for HTN. Little effect on BP

Table 1 Non specific non steroidal antiinflammatory agents Drug

Dosage

Onset

Duration

Cardioprotective dose PO

Hydrolyzed to active

81mg/day;Other Aspirin

indications PO/PR 650 mg Time to peak 1-2 q4-6 hours Pediatric PO/PR hrs

4-6 hrs

10-15 mg/kgrtlose q4-6

(Motrin, Advil)

tuprofen

IV(Caldolor)

Naproxen

(Naprosyn, Meve)

drug in Gl tract/blood

Hepatic metabolism to conjugates excreted in urine

hours Ibuprofen

Metabolism/excretion

Comments Max daily dose 4 g. Crosses placenta

and enters breast milk

Max daily dose PO 200-400 mg q4-6 hours Pediatric 4-10 mg/kg/dose IV 400-&00mgq6 hours

2400 mg, 3200 mg

30-60 min

analgesic, <7 days as

PO 4-6 hrs

antiinflammatory

Hepatic, strong

inhibitor of CYP2C9

for IV form.

Pregnancy risk C/D>30 wks.

Breastfeeding not recommended

PO 500 mg, followed by

250 mg q6-8 hours Age 212:10 mg/kgrtlay in 2 divided doses

Analgesia 1 hour,

antiinflammatory 14 days

Max dally adult Analgesia 7 hrs,

Hepatic, to inactive

12 hrs

urine

antiinflammatory metabolites excreted in

dose 1,000 mg/day after first day.

Pregnancy risk Q

breastfeeding not recommended

Max daily dose 120 mg(*). Do not exceed 5 days Ketorolac (Toradol)

IV or IM 30 mg q6 hours

10 min, peak

effect 1-2 hrs

therapy. First dose

6-8 hrs

Hepatic, 60% excreted IM may be 60 mg. unchanged in urine

PO formulation also aval labia

Pregnancy risk C, breastfeeding not recommended

Diclofenac (vdtarer% Cataflam)

Max dose

Depends on PO 50 mg q8-12 hours

product used, 0.5-5 hrs for

sustained release product

Elimination ha If-life 2 hrs

Hepatic, to weakly

active metabolites, excreted In urine

150mg/day.

Pregnancy risk C/D >10 wks,

breastfeeding not recommended

(*) This dose is tor patents < 65 yrs, or > 50 kg BW. Patients >65yrs, or weiqh <50 kg should receive lV or IM 15 mg {first dose maybe 30 mg}, maximum of 60 mg/day

Table 1 Oral agents for type 2 DM Drug Glimepiride (Amaryl®) Glipizide

(Glucotrol®)

Dose PO 1-4 mg once daily

PO 5-20 mg/day

once or in divided doses

PO 1.5-20 mg/day

Glyburide(DiaBeta®) once orin divided doses

Onset Duration Peak eff ect 2-3 hrs

Peak 1-3 hrs

15-60

minutes

24 hrs

Metabolism/excretion Hepatic Via CYP2C9 to one

active metabolite, both excreted urine and feces

Hepatic Via CYP2C9 to Inactive

12-24 hrs metabolites excreted mostly In urine

Comments Dose reduction In severe renal failure

Dose reduction in severe hepatic disease

Hepatic via CYP2C9 to weakly

Not recommended with

urine and feces

hepatic disease

<24 hrs active metabolites excreted In

CrCl < 50, caution in

Table 2 Newer generation oral agents for type 2 DM (Dipeptidyl Dipeptidase Inhibitors) Drug Silagliptin

(Januvia®) Saxagliptin

Dose PO 100

mg/day

Onset Time to

peak 1-4 his

PO 2.5-5 Time to

(Onglyza®) mg/day peak 2 hrs Linagliptin

PO 5

(Tiadjenta®) mg/day

Time to

peak 1.5 hrs

Duration half-life 12 his

24 hrs half-life 12 hrs

Metabolism/excretion

Comments

Excreted unchanged into urine (80%), some

Dose reduction required in

Hepatic via CYP3A4 to active metabolite;

2.5 mg dose in renal failure.

minor hepatic metabolism via 3A4 and 2C8

excreted in the urine (75%)

80% excreted unchanged into feces

renal failure

Caution with 3A4 inhibitors

May cause hyperuricemia and increased serum lipids

Table 1 Thienopyridines/ADP inhibitors Drug

Dose

Onset Duration 7-10

PO 300-600 mg

Clopidogre loading dose for PCI; (Plavix®) 75 mg dally for

days

2-5 hrs lifespan of

maintenance

Tldopidine (Tlclid®)

Prasugrel

PO loading dose 500 mg, then 250 mg

BID for maintenance

PO loading dose 60 mg, then 10 mg

(Effient®) daily for

maintenance

platelet 7-10 6 hrs

with

loading dose

Hepatic conversion via 2CI9 to active form, other cytochromes/ester hydrolysis to

inactive metabolites excreted in urine and feces

Comments

Caution if severe hepatic disease

days

Hepatic primarily via CYP3A4; 1 active

Hematdogic toxicity more

of

and feces

dopidogrel

lifespan platelet

30 min

Metabolism/excretion

7-10 days

lifespan of

platelet

metabolite; excreted in the urine (60%)

commcn than with

Intestinal/serum conversion to inactive

Not recommended in

2B6 to active form; excreted in the urine

of HTN and atrial

metabolite, then converted via 3A4 and (68%) and feces

patients >75 years. Risk fibrillation!--10%)

See Table Durg Enoxaparin

Indication Total hip/knee

Duration

oltherapy

40 mg/day or 30 mg BID start 12-24 hrs postop

At least 10 days

Abdominal surgery

40 mg/day started day of surgery

At least ID days

Multiple trauma

40 mg/day

replacement

Immobility in medical illness Dalteparin

Dose (subcutaneous)

Total hip/knee replacement

Abdominal surgery Multiple trauma Immobility in medical illness

40 mg/day 2.500 units 4-8 hrs postop then 5,000 units/day 2,500 units 1-2 hrs postop (if low risk) then pef day, may use 5,000 units if high risk

Usually 6-11 days

5-10 days 5-10 days

5,000 units/day 5,000 units/day

Duration of therapy may be modified if patient is being switched to warfarin, or risk of DVT has passed.