Propofol o Short-acting lipophilic sedative hypnotic o Actions on GABA-A receptors, potentiates Cl current o Adverse effects: hypotension, apnea, movement, stinging o Rapid induction and maintenance o Big drops in BP due to vasodilation Etomidate o Nonbarbiturate Nonbarbiturate hypnotic, no analgesic analgesic activity, activity, minimal minimal cardiovascular cardiovascular effects effects o Adverse effects: site pain, movements, opsoclonus, adrenal suppression Ketamine o Inhibits NMDA receptors for induction o Dissociative anesthesia, nystagmus o Unpleasant hallucinations can occur o Increases BP, HR, CO Succinylcholine o Depolarizing skeletal muscle relaxant, depolarizes muscle at motor endplate and causes sustained muscle paralysis, no effect on consciousness or pain o Black box warning for hyperkalemia, ventricular dysrhythmias, cardiac arrest in children/adolescents; usually had undiagnosed skeletal muscle myopathy like DMD o Fastest onset and shortest duration of action of all relaxants o Hyperkalemia because ACh receptor kept open, allowing efflux of K o Binding to nicotinic ACh receptor opens it and get depolarization, Ca release from SR; it acts longer than ACh and is not broken down by AChE so cell isn’t allowed to repolarize; Ca removes from muscle, causing relaxation and flaccidity after transient fasciculations (Phase I) o Blood concentration of drug exceeds therapeutic window, nerve terminal gets desensitized, myocyte now less sensitive to drug, and membrane can repolarize and become depolarized depolarized again (Phase II) II) Rocuronium o Nondepolarizing Nondepolarizing skeletal skeletal muscle relaxant; relaxant; cholinergic cholinergic receptor receptor antagonist; antagonist; inhibits depolarization o Adverse effects: transient hypotension, HTN Fentanyl o Opioids open K channels and close Ca channels to prevent release of neurotransmitters o Mu receptor agonist, much more potent than morphine o Highly lipid soluble, effects are more localized Hydromorphone o Semi-synthetic mu receptor agonist Neostigmine Neostigmine o Competitive inhibitor of cholinesterase, decreased hydrolysis of ACh, increasing amounts in synaptic cleft so it can compete for same binding sites as nondepolarizing neuromuscular blocking agents; reverses blockade o Cholinergic side effects like bradycardia, bronchospasm, increase in gut motility (which is why glycopyrrolate often given with it) Glycopyrrolate o Competitive antagonist of ACh on automatic effectors innervated by postganglionic nerves
Inhibits salivation, secretions, bradycardia (prevents neostigmine-induced), hypotension o Side effects would be anticholinergic symptoms (red as a beet, etc.) Atropine o Antimuscarinic; inhibits ACh at parasympathetic sites in smooth muscle, CNS, secretory glands; increases CO and dries secretions o Increases action at SA node, opposes action of vagus nerve, blocks ACh sites, decreases bronchial secretions; causes mydriasis o Reversed by physostigmine Famotidine o H2 receptor blocker o Inhibits stomach acid production, no effects on CYP450 o Reduces risk of aspiration pneumonitis Metoclopramide o D2 blocker; antiemetic because it has antagonist activity at D2 receptors in chemoreceptor trigger zone in CNS o Increases peristalsis, tone and amplitude of contractions, relaxes pyloric sphincter and bulb, and increases LES tone o Treats nausea, vomiting, migraine, gastroparesis o Contraindicated in pheochromocytoma, Parkinson’s, bowel obstruction Ondansetron o Serotonin receptor blocker o Treats nausea and vomiting due to chemo or surgery o Side effects are diarrhea, headache, sleepiness, itching, QT prolongation, serotonin syndrome possible Phenylephrine o A1 adrenergic receptor agonist o Decongestant, dilates pupils, increases BP; reflex bradycardia o Can use to increase BP in hypotensive patient during surgery o Mainly metabolized by MAO Ephedrine o Sympathomimetic amine, acts on SNS; mainly will indirectly stimulate adrenergic receptor system by increasing norepi activity at postsynaptic alpha and beta receptors o Prevents low BP during spinal anesthesia; also used for asthma, narcolepsy o
Local anesthetics MOA and factors affecting block (Ch. 11)
LA blocks AP by inhibiting voltage gated Na channels Blocks conduction of neurons by decreasing rate of depol in response to excitation, preventing threshold potential; no effect on resting potential Only uncharged form can enter, and then charged form can bind inside Bind to activated and inactivated Na channel states more readily than resting state; dissociation from inactivated slower than from resting; repeated depol produces more effective anesthetic effect (use dependent or frequency dependent) Lower pKa greater percent un-ionized fraction at given pH Bicarb added to LA to increase un-ionized fraction to speed up onset
Lipid solubility (expressed as partition coefficient) correlates with potency and duration of action; duration also affected by protein binding Larger diameter nerve fiber = rapid nerve conduction, myelin = increased conduction velocity Conduction blockade absent if at least 3 nodes of Ranvier in a row are exposed to enough LA LA diffuses from outside to inside of nerve, so nerve fibers outside (mantle) blocked first, which are mostly proximal structures
Depolarizing neuromuscular blocking drugs (Ch. 12)
Only succinylcholine is used clinically, and it has rapid onset and short duration of action Perfect for tracheal intubation Mimics action of ACh, get sustained depol of postjunctional membrane – get paralysis because postjunctional membrane and inactivated Na channels cannot respond to subsequent releases of ACh Depolarizing part also called Phase I blockade; initially see fasciculations; also get leakage of K from inside of cells, which in right setting can lead to acute hyperkalemia Phase II is when membrane is repolarized but not responding normally to ACh Plasma cholinesterase (pseudocholinesterase) breaks it down rapidly; none at NMJ so SCh goes away by diffusion away from NMJ into extracellular fluid (some MG or chemo drugs might prolong paralysis by decreasing plasma cholinesterase activity) Atypical plasma cholinesterase also exists Adverse effects: cardiac dysrhythmias, fasciculations, hyperkalemia, myalgia, myoglobinuria, increase intraocular and intragastric pressure, trismus Cannot give to pt for 24-72 hr after burns, trauma, extensive denervation/spinal cord damage due to risk of hyperkalemia and cardiac arrest Atropine before SCh dose can prevent cardiac dysrhythmias Magnesium can prevent fasciculations, but not myalgia
Monitoring effects of nondepolarizing neuromuscular blocking drugs (Ch. 12)
Elimination of two to three twitches of TOF correlates with acceptable skeletal muscle relaxation, if all twitches are absent more NMBD should not be given For NMBD TOF twitches show fade, while SCh stays the same height Double burst suppression – two bursts of three stimulations, you see two separate twitches Tetanus – NMBDs show fade while SCh shows decrease equally in phase I
Preop evaluation and medication overview (Ch. 13)
Pt or family hx of anesthesia adverse events such as postop nausea/vomiting, prolonged emergence or delirium, or MH/pseudocholinesterase deficiency must be noted Recommended to continue aspirin throughout periop period, and clopidogrel restarted ASAP Well controlled asthma does not increase risks Steroids or B-agonist preop can decrease bronchospasm after intubation
Anesthetic technique and inhalational induction (Ch. 14)
Preoxygenation can help with safety during periods of apnea during induction
Rapid sequence intubation involves preoxygenation, cricoid pressure, opioid to blunt hypertensive and HR responses to laryngoscopy/intubation (ex. remifentanil), neuromuscular blocking agent, then intubation Patent airway evidence if upper part of chest expands and reservoir bag partially empties during inspiration, reservoir bag refills during expiration, capnography shows waveforms of 0 at inspiration and peak of >20 at expiration, pulse ox shows >95%, bilateral breath sounds present Inhalation of sevoflurane can replace rapid-sequence induction Desflurane is also rapid but is too irritating to airway to use for induction Sevo can be used when difficulty airway anticipated Nitrous does not improve induction; benzos can speed up inhaled induction, opioids inhibit due to apnea
Airway anatomy and innervation of larynx (Ch. 16)
Resistance to airflow in nose twice of that in mouth, accounts for 2/3 of airway resistance Ophthalmic and maxillary divisions of CN V innervate nasal mucosa Pharynx is divided into nasopharynx, oropharynx, and hypopharynx; soft palate separates nasopharynx and oropharynx; epiglottis separates oropharynx and hypopharynx; innervated via CN IX and X; tongue is predominant cause of resistance in oropharynx (increased by relaxation of genioglossus during anesthesia) Larynx in adult is between 3-6 th cervical vertebrae, modulates sound and separates trachea from esophagus during swallowing – if exaggerated becomes laryngospasm Larynx made up of muscles, ligaments, cartilages (thyroid, cricoid, arytenoids, corniculates, epiglottis) Superior laryngeal nerve (internal division) sensory for epiglottis, base of tongue, supraglottic mucosa, thyroepiglottic joint, cricothyroid joint; no motor Superior laryngeal nerve (external division) sensory for anterior subglottic mucosa; motor for cricothyroid muscle Recurrent laryngeal nerve sensory for subglottic mucosa, muscle spindles; motor for thyroarytenoid, laternal cricoarytenoid, interarytenoid, and posterior cricoarytenoid muscles
Laryngeal mask airways (Ch. 16)
Difficult facemask ventilation predictors are age >55, BMI >26, beard, no teeth, history of snoring, repeated attempts at laryngoscopy, Mallampati class III-IV, neck radiation, male gender, limited ability to protrude mandible
Preop preparation (Ch. 17)
Need to mention possible complications such as bleeding, infection, nerve damage, and minor postdural puncture headache Spinal anesthesia used for surgery of lower abdomen, perineum, and lower extremities Epidural anesthesia is segmental, so it may be suboptimal for procedures involving lower sacral roots; can be used to supplement GA especially for thoracic or upper abdomen procedures; useful to do continuous epidural anesthesia postop to allow for pain management (better than opioids); continuous epidural also used for labor pain
Absolute contraindications to neuraxial anesthetics are infection at site, elevated ICP, bleeding disorder; would want to use cautiously in patients with MS; cautious use in patients with mitral or aortic stenosis since they are intolerant of decreases in SVR
Epidural anesthesia (Ch. 17)
Sitting position is best to see midline, but lateral decubitus has decreased incidence of venous cannulation Kids get any epidural after GA Midline and paramedian approaches can be used for lumbar or low thoracic epidural; midline more popular because of simpler anatomy, passage of needle through less sensitive structures Thoracic epidural usually done via paramedian approach because spinous processes are angulated; initial step is contacting lamina and then going from there Most important step to ID epidural space is engaging the ligamentum flavum (loss of resistance technique; difficult to inject saline or air bubble) Hanging-drop technique places small drop of saline in hub of epidural needle, and then it’s retracted into needle by negative space in epidural space once it passes through ligamentum flavum In single shot LA, give test dose of LA like lido with epi Factors affecting spread of epidural anesthesia are dose (vol x conc) and site of injection Thoracic is more symmetrical anesthesia, lumbar is more cephalad spread Duration depends on choice of LA and whether vasoconstrictor was added; common choices are chloroprocaine (rapid onset and short duration), lidocaine (intermediate onset and duration), and bupivacaine/ropivacaine (slow onset and prolonged duration) Epinephrine will decrease vascular absorption of LA from epidural space Opioids given to enhance anesthesia and provide postop pain control; lipid solubility of opioid critical in determining selection (morphine spreads rostrally in CSF; fentanyl is lipophilic and rapidly absorbed with little rostral spread) Lipophilic opioids have limited selective spinal activity in lumbar epidural region because the site of action (dorsal horn of spinal cord) is several segments rostral to site of injection Sodium bicarb will favor nonionized form of LA and promote rapid onset (however, alkalinizing bupivacaine is not recommended because it precipitates at alkaline pH) Major site of action is spinal nerve roots where dura is thinner Cranial nerves cannot be blocked because epidural space ends at foramen magnum; but can cause issues breathing due to phrenic nerve arising from C3-C5 if done up high; high epidural anesthesia will still have miosis if opioids on board, while total spinal will lose that response and have pupillary dilation Main effect is SNS block, preload reduction, decreased CO and BP; PNS of heart not impaired so vagal reflexes can be significant Potential complications are epidural hematoma and abscess, neural injury, injection into subarachnoid space, etc.
Peripheral nerve injury (Ch. 19)
Ulnar is the most frequently injured, followed by brachial plexus, lumbosacral nerve root, and spinal cord
Ulnar issues would result in inability to abduct or oppose fifth finger, decreased sensation in fourth and fifth fingers, atrophy of intrinsic hand muscles, claw-hand
Electrocardiography and capnography (Ch. 20)
With MI, T wave affected first, followed by ST segment changes; myocardial necrosis shown by production of Q waves Lead V5 alone can detect 75% ischemic episodes in men 50-60; adding V4 increases sensitivity to 90%; combining leads II, V4, V5 will detect up to 96% CO2 tells you if patient is being ventilated, estimates PaCO2, evaluates dead space CO2 waveform has inspiratory baseline, expiratory upstroke, expiratory plateau, and inspiratory downstroke Sustained CO2 waveform (>30) confirms ET tube placed in trachea, whereas if it’s accidentally placed in esophagus it will disappear
Temperature monitoring (Ch. 20)
Most GA has vasodilation, which causes heat to go from core of body to periphery; core temp will decline by 1-1.5C in first hour after induction, and then keeps decreases if incision is large, environment cold, initial temp was low, etc. Hypothermia can delay recovery, shivering increases O2 utilization, BP, and HR, and even MI in elderly, coagulation times and wound healing impaired Best core temp monitors are PA catheter which measures within pulmonary artery or tympanic membrane monitor which measure temp of carotid artery; bladder fluid temp is close to core, while rectal is poor estimate; Esophageal can be used; axillary and skin are prone to artifacts
Standards for basic anesthetic monitoring (Ch. 20) Composition of FFP and cryoprecipitate (Ch. 24)
FFP is fluid portion from single unit of whole blood that is frozen within 6 hours of collection All coagulation factors (except platelets) are present, which is why it’s used for hemorrhage from coagulation factor deficiencies FFP used with RBCs in trauma patients and to rapidly reverse warfarin; may be used in transfusion-related acute lung injury Cryoprecipitate is fraction of plasma that precipitates when FFP thawed; used to treat hemophilia A or hypofibrinogenemia Cryoprecipitate contains factor VIII and fibrinogen
Anesthesia for lung resection (Ch. 27)
Risk factors with increased periop morbidity includes extent of lung resection (pneumonectomy > lobectomy > wedge resection), age >70, and inexperience of surgeon Predicted postop FEV1 and DLCO <40% is associated with poor outcomes; need exercise study Smoking cessation for 12-24 hrs before surgery will decrease level of carboxyhemoglobin, shift O2 dissociation curve to right, and increase O2 available to tissues; to improve mucociliary clearance would need cessation for 8-12 weeks Usually do IV propofol, then volatile anesthetics because they will depress airway reflexes but don’t inhibit regional hypoxic pulmonary vasoconstriction so you maintain adequate PaO2
N2O can exacerbate existing pulmonary HTN; contraindicated when it can potential to expand closed airspace Need nondepolarizing NM blocking drugs to allow for ET intubation Ketamine or etomidate useful for those with hemodynamic instability Thoracic epidural catheter used for postop pain control Fluid should be limited to avoid acute lung injury Isolating lungs can be achieved with double-lumen ET tubes and bronchial blockers Right main bronchus is shorter and wider than left
Neurophysiology (Ch. 30)
Cerebral blood flow usually 15% of CO Determinants of CBF are CMRO2, cerebral perfusion pressure and autoregulation, PaCO2, PaO2, and anesthetic drugs CMRO2 (metabolic rate) directly influences CBF; reduces by hypothermia and most anesthetic drugs; CMRO2 and CBF can be increased by seizure activity CPP = MAP – ICP or CVP Autoregulation maintains CBF between CPP of 50-150 Chronic HTN or sympathetic stimulation shifts the curve to the right, they have higher minimum CPP to maintain CBF; anesthetics shift curve to the left, which is some safety from decreases in MAP that occur during surgery Inhaled anesthetics are potent cerebral vasodilators and can impair autoregulation at high doses Autoregulation maintained at concentrations less than 1 MAC IV anesthetics do not disrupt autoregulation CBF changes by 1 mL/100g/min for every 1mmHg change in PaCO2 from 40mmHg CBF returns to normal within 6-8 hrs, however; aggressive hyperventilation should be avoided because of cerebral ischemia risk Decreases in PaO2 (<50mmHg) result in exponential increase in CBF IV anesthetics are cerebral vasoconstrictors and reduce CMRO2 and CBF, so often use things like thiopental, Propofol, and etomidate for neurosurgery Ketamine changes depending on context – alone it increases PaCO2, CBF, and ICP, but together that doesn’t happen Benzos and opioids decreases CMRO2 and CBF a2-agonists (clonidine, dexmedetomidine) do not cause significant respiratory depression; they do reduce arterial BP, CBF, and CPP Volatile anesthetics are potent cerebral vasodilators; get increases in CBF
Intracranial pressure (Ch. 30)
Intracranial compartment made up of brain matter, CSF, and blood Elevated ICP is anything >15mmHg Initial increase in volume causes CSF to go into spinal canal; then ICP rises and cerebral blood vessels compressed Most IV anesthetics reduce CMRO2 and CBF, which reduces ICP Neuromuscular blocking agents do not affect ICP unless they induce release of histamine or hypotension
Pediatric airway (Ch. 34)
Tongue is larger and can more easily obstruct airway Cricoid ring is narrowest part of airway (instead of laryngeal aperture at vocal cords in adults) – but recent MRI showed that narrowest part is glottis like in adults Larynx is higher at C4 instead of C6 Epiglottis is omega-shaped and soft Face mask is more commonly used in kids
Malignant hyperthermia: definition, causes, treatment (Ch. 37)
Some precautions to have in place are cooling via bladder irrigation, “clean” airway equipment and O2 delivery systems, minimum of 36 vials of dantrolene Blood gases recommended to guide therapy
Oxygen supplementation: nasal cannula vs face mask (Ch. 39)
Choice of O2 delivery determined by level of hypoxemia, surgical procedure, patient compliance Nasal cannula can do 1-6 L O2 Each L/min of O2 flow through NC increases FiO2 by 0.04, with 6 L/min resulting in ~0.44 FiO2 Now there are high-flow NC that can deliver up to 40 L/min O2 For patients with abdominal surgery, application of CPAP can reduce incidence of intubation, pneumonia, infection, and sepsis Contraindications to PPV in PACU are hemodynamic instability, life-threatening arrhythmias, altered mental status, high risk for aspiration, inability to use nasal or face mask, and refractory hypoxemia
Mechanical ventilation (Ch. 41)
Used to treat respiratory failure (impaired O2), ventilatory failure (impaired CO2 excretion), and airway protection Helps reduce work of breathing, reverse progressive respiratory acidosis or hypoxemia, reduce risk for aspiration, and ensure patent airway with severe neck/facial swelling/trauma Continuous mandatory – delivers set TV at set RR, predictable MV; assist-control is similar except any independent breaths are supported to full TV; CMV is most commonly used in ICU Synchronized intermittent mandatory – TV and RR are set, but ventilator tries to synchronize mandatory breaths with patient’s spontaneous attempts Pressure support – relies on patient’s intrinsic drive, no preset TV; delivers positive pressure breath to assist when they try to breathe; amount of pressure usually 5-20 cm H2O; patient must have intact respiratory drive and no residual NM blockade Positive end-expiratory pressure – applied throughout the respiratory cycle; increases mean airway pressure and prevents atelectasis; increases FRC and improves pulmonary compliance; typical PEEP is 5- 20 cm H2O Postsurgical and postpercutaneous coronary intervention patients are exception to rule that must be on minimal vasopressors before stopping mechanical ventilation because their issues will likely resolve after their procedure, rather than being intrinsic to a disease state Trial of weaning o Inspired O2 concentration required to maintain O2 sat must be less than 40-50%
Strong enough to generate adequate TV; have patient inhale and that force should be at least -20, or VC of at least 10 mL/kg; with normal breathing, TV of at least 5 and MV of no more than 10 o Must be able to protect airway against aspiration and clear their own secretions; need gag reflex and intact mental status Patients weaned faster with spontaneous breathing trials, and once a day is enough of a trial o
Pharmacologic management of chronic pain (Ch. 43)
Tylenol, NSAIDs, aspirin are first steps in treatment NSAIDs and aspirin inhibit COX, decreased levels of prostaglandins TCAs (ex. nortriptyline, desipramine) and newer SNRIs are useful for neuropathic pain; side effects are dry mouth, urinary retention, worsening preexisting heart block Anticonvulsants (ex. gabapentin, pregabalin) are used for neuropathic pain; side effects are dizziness, somnolence, peripheral edema Opioids used chronically can worsen pain by induced hyperalgesia; usually give long-acting opioid for continuous analgesia, and a small dose short-acting for breakthrough pain
