Paul’s Anesthesiology ITE Review

Clinical Signs of General Anesthesia

• Induction

1. State of sedation → patient is calm and easily arousable, with the eyes generally closed
2. May enter a state of paradoxical excitation → purposeless or defensive movements, incoherent speech
3. Irregular respiratory pattern → Loss of response to oral commands + loss of skeletal muscle tone → apnea
4. Oculocephalic, eyelash, and corneal reflexes are lost, but the pupillary eye reflex remains

• Emergence

1. Phase 1: Return of spontaneous respiration
2. Phase 2:

• Salivation (CN 7, 9) and tearing (CN 7) → nonlocalizing responses to painful stimulation
• Return of grimace (CN 5, 7) or swallow/gag/cough (CN 9, 10)
• Defensive movements (e.g. reaching for ETT) → eyes may still be closed
• Extubation possible

3. Phase 3: Spontaneous eye opening + Response to oral commands

• Source: Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med 2010; 363:2638-2650

Succinylcholine-induced Myalgia and Fasciculation

• Myalgias: high incidence (50% at 24-48h, 33% on day 3, can last up to a week)

• Lower incidence in: children, elderly patients, athletes, and pregnant women
• Effective interventions for prevention of succinylcholine-induced myalgia:

• NSAIDs (most effective)
• High-dose succinylcholine (1.5 mg/kg)
• Lidocaine (1.5 mg/kg)
• Defasciculating dose of rocuronium (0.03 mg/kg ← 10% of ED95 = 10% of 0.3 mg/kg)

• Timing: 2-3 minutes before succinylcholine administration
• Adverse effects of defasciculating dose: blurred vision, diplopia, heavy eyelids, weakness, difficulty breathing and swallowing, lower voice

• Opioids don’t make a difference

• Fasciculations: incidence 90%

• No clear link between fasciculations and myalgia

• Source: Schreiber JU, Lysakowski C, Fuchs-Buder T, Tramèr MR. Prevention of succinylcholine-induced fasciculation and myalgia: a meta-analysis of randomized trials. Anesthesiology. 2005;103(4):877-884.

Lateral Patient Position: Complications

• Eye and ear injury if not free of pressure
• Neck pain from non-neutral spine
• Ventral circumduction of the dependent shoulder → suprascapular nerve injury

• Presentation: diffuse, dull shoulder pain
• Prevention: chest roll (“axillary roll”)
• Diagnosis: blocking the nerve at the notch producing pain relief
• Treatment: if conservative treatment fails, may need to resect some ligament to decompress nerve

• Source: Barash 8e Ch 29 p. 818-819

Endoscopic Retrograde Cholangiopancreatography (ERCP)

• Procedure: biliary and pancreatic duct systems are instrumented → stone removal, stents
• Complications: acute pancreatitis, hemorrhage, perforation
• Anesthetic technique: requires general anesthesia or deep sedation

• If sphincter of Oddi manometry is performed, avoid drugs that affect sphincter pressure: atropine, glycopyrrolate, glucagon, opioids 

• Most opioids increase biliary sphincter (of Oddi) tone → increased common bile duct pressure

• Can be reversed by naloxone (except meperidine)

• Treatment: butorphanol → mixed agonist-antagonist

• Mechanism: Partial MOP antagonist, KOP agonist, SOP agonist
• No biliary sphincter effects → preferred narcotic for pain from biliary colic

• Additional considerations: patients may be tachycardic from glucagon or IV hyoscyamine

• These are antispasmodics that reduce motility → given to improve operating conditions

• Source: Barash 8e Ch 33 pp 889-890

Shock Wave Lithotripsy

• Procedure: focused sound waves break stones into smaller pieces → pieces expelled through urination
• Complications: positioning-related, hypothermia, risk of kidney injury, subcapsular hematoma

• Less successful in: obese patients, extremely hard stones (cysteine and calcium oxalate)

• Anesthesia: topical local anesthesia and analgesia/sedation
• Absolute contraindications

• Bleeding disorder or anticoagulation
• Pregnancy

• Relative contraindications

• Large calcified aortic or renal artery aneurysms
• Untreated urinary tract infection
• Obstruction distal to the renal calculi → cannot clear stone pieces
• Pacemaker, ICD, or neurostimulation implant → interference
• Morbid obesity → high failure rate

• Source: Barash 8e Ch 50 pp 1432-1433

IV Contrast Agents

• Radiologic contrast media: iodinated compounds → classified according to

• Osmolarity (high, low, or iso-osmolar)
• Ionicity (ionic/nonionic) → nonionic = fewer adverse effects, less discomfort on injection
• Number of benzene rings (monomer or dimer)

• MRI contrast agents: chelated metal complexes containing gadolinium, iron, or manganese

• Divided by ionicity into ionic and nonionic compounds

• Renal Adverse Reaction → contrast-induced nephropathy (CIN)

• Cr ↑ 0.5 mg/dL or ↑ 25% from baseline within 72h after iodinated contrast administration
• Risk factors: chronic kidney disease (most important), diabetes, hypertension, gout, nephrotoxic drugs
• Prevention of CIN:

• Adequate hydration, sodium bicarbonate infusion
• Avoidance of nephrotoxic drugs (NSAIDs, aminoglycosides, diuretics)

• Hypersensitivity Reactions:

• Reactions more common with iodinated agents (radiologic) vs. gadolinium-based (MRI)
• Gadolinium-containing compounds can cause nephrogenic systemic fibrosis (NSF) in patients with existing kidney disease

• Fibrosis of skin and internal organs (similar to scleroderma)

• Source: Barash 8e Ch 33 p 885

Blood Storage

• FDA Requirement: more than 70% of blood bank units should have a 24-hour RBC recovery ≥ 75%
• Cooled to 4°C to decrease cellular metabolism
• CPD and CP2D → 21-day shelf life
• CPDA-1 added (extends shelf life to 35 days)

• Citrate → binds calcium → anticoagulant

• Normally cleared by liver → bicarbonate is a byproduct → metabolic alkalosis with MTP
• With large transfusions → liver can’t clear fast enough → citrate binds Ca2+ → low Ca2+

• Hypocalcemia → hypotension, prolonged QT, tetany, weakness, laryngospasm

• EDTA is not used as an anticoagulant with blood because it irreversibly binds Ca2+

• Phosphate → buffer and substrate for ATP
• Dextrose → source of cellular energy (Glc 400 at donation → Glc 100 at day 35)
• Adenosine → substrate for ATP

• “Additive Solution” → AS-1, AS-3, and AS-5 → contain adenine, glucose and saline → added to CPD or CP2D whole blood that has plasma removed → 42-day shelf life
• Potassium: increases from 4 mEq/L at donation → 76 mEq/L at 35 days → can cause hyperkalemia
• 2,3-BPG falls below 1 μM/mL → leftward shift of oxyhemoglobin dissociation curve (lower P50)
• pH decreases: CO2 accumulates, glucose is converted to lactate (anaerobic metabolism), acidic citrate

Methemoglobinemia

• Methemoglobinemia → elevated levels of metHb which is formed when the iron in hemoglobin is oxidized from Fe2+ to Fe3+ → high oxygen affinity → decreased oxygen delivery (decreased SvO2 only when measured via co-oximetry)

• No symptoms till metHb reaches 30%
• Normally, erythrocyte methemoglobin reductase reduces Fe3+ back to normal Fe2+
• Triggers: local anesthetics (benzocaine, prilocaine), antibiotics, metoclopramide, nitrates, nitrites

• Benzocaine → non-dose-dependent (can happen even with normal doses!)
• Prilocaine (EMLA cream) → dose-dependent (happens only with large doses)

• Purposefully induced with amyl nitrate and sodium nitrite to treat cyanide toxicity → Fe3+ of metHb binds cyanide avidly and removes it from cytochrome c oxidase

• Congenital methemoglobinemia → decreased enzymatic activity of methemoglobin reductase

• Generally patients are cyanotic, but otherwise asymptomatic
• Avoid methemoglobin-inducing drugs: benzocaine, prilocaine, quinine, metoclopramide, sulfonamides, and dapsone

• EMLA cream: contains prilocaine → contraindicated in congenital methemoglobinemia

• Treatment: methylene blue (1-2 mg/kg over 3-5 minutes) → acts as an electron acceptor for NADPH methemoglobin reductase → enhances enzyme activity 5-fold → more metHb reduced to Hb

• However, in G6PD deficiency → avoid methylene blue → induces hemolysis
• Methylene blue is a potent MAO inhibitor → may trigger serotonin syndrome in susceptible patients Ref
• G6PD deficiency: use ascorbic acid (vitamin C) instead

• MetHb has an absorbance of 630 nm (similar to deoxyhemoglobin) → SpO2 reads 85% regardless of true SaO2
• On ABG: PaO2 (dissolved oxygen content) will be normal (like in carbon monoxide poisoning)
• Diagnosed by blood gas analysis with co-oximetry

Transient Neurologic Symptoms (TNS)

• Happens after intrathecal (spinal) administration of local anesthetics
• Pain or sensory abnormalities in the lower back, buttocks → radiating to the lower extremities
• Symptoms occur within 24 hours postoperatively and resolve spontaneously in the 4th/5th day
• Risk factors:

• Intrathecal lidocaine and mepivacaine (far less frequent with bupivacaine)

• Appears unrelated to dose/concentration and baricity (Barash)

• Other risk factors: Lithotomy position, men, ambulatory procedures, early ambulation
• Needle type: reduced by a double-orifice needle

• Management

• Verify absence of motor/sensory block, bowel/bladder dysfunction → signs of hematoma/abscess
• If no other symptoms are present, reassure patient that the pain will improve in a few days
• NSAIDs and trigger point injections are effective for myofascial pain, but not for neuropathic pain

• Source: Barash 7e Ch 21 & 34, Miller 8e Ch 56

High Altitude Physiology

• High altitude → lower Patm(FiO2 remains constant) → decreased PaO2 55 mmHg → peripheral chemoreceptors stimulated (sensitive to oxygen) → hyperventilation → low PaCO2 30 mmHg (relative excess of bicarbonate ions) → low PaCO2 in CSF → inhibits central chemoreceptors in medulla → decreased ventilatory drive → AMS

• Oversimplified explanation; real pathogenesis is complex, involves biochemical cell changes

• Alveolar gas equation: PAO2 = FiO2 (Patm - PH2O) - PACO2/RQ

• E.g. @ 10,000 ft and PACO2 = 32 → Patm = 525 mmHg ⇒ PAO2 = 0.21 * (525 - 47) - (32/0.8) ⇒ 60 mmHg

• After 72 hours: renal excretion of bicarbonate ions → alkalosis corrects → central chemoreceptors now resume ventilatory drive → increased ventilatory rate maintained even after acclimatization
• Acute mountain sickness (AMS): headache, nausea, vomiting, insomnia, dyspnea, peripheral edema

• Prophylaxis: acetazolamide or dexamethasone
• Acetazolamide (carbonic anhydrase inhibitor) → promotes excretion of bicarbonate ions → metabolic acidosis → counteracts respiratory alkalosis → resumed ventilatory drive (initially, the low PaCO2 and, consequent, relative excess bicarbonate in CSF was preventing medullary central chemoreceptors from driving ventilation; now that bicarb is being excreted, this drive resumes)

• Shifts the ventilation-CO2 response curve to the left (higher MV for a given pCO2)

• High-altitude pulmonary edema (HAPE): hypoxic pulmonary vasoconstriction → increased pressure in pulmonary vasculature → pulmonary edema

• Treatment: pulmonary vasodilators (nifedipine and inhaled β2-agonists)

• High-altitude cerebral edema (HACE): hypoxia → increased cerebral blood flow → cerebral edema
• Hypoxia → EPO → increased hemoglobin production → increased viscosity → higher risk of blood clots
• Cardiac output: increases initially but returns to normal after acclimatization

Pharmacokinetic Principles

• Back-end kinetics (end of an infusion)

• Decrement time: time required to reach a specific concentration after stopping infusion

• Context-sensitive half-time is a specific subtype (time to 50% decrement) of decrement time

• E.g. fentanyl and isoflurane have the longest context-sensitive half-life (Figures)

• E.g. decrement time of plasma propofol concentration to 1.5 mcg/mL (awakening) → usually shorter than context-sensitive half-life

• Terminal half-life: half-life of elimination after the tissue concentration has equilibrated with plasma
• Time constant: time it takes for a system to change a given parameter by 63%

• Useful parameter to calculate how long it takes for a newly dialed concentration of gas anesthetic to equilibrate with the gas in the circuit
• Time constant = circuit volume ÷ fresh gas flow (FGF)
• 1 time constant → 63% change ⇒ 2 time constants → 86% change ⇒ 3 time constants → 95% change

Figures: Pharmacokinetics of opioids (above). Pharmacokinetics of inhaled anesthetics (below)

Fresh Frozen Plasma (FFP)

• Contains all clotting factors and plasma proteins
• Least stable factors: factors 5 and 8 → degrade above 4°C → reason for freezing

• Can be transfused for up to 5 days after thawing, but 50% decrease in factors 5 and 8
• Factor 8: produced in liver and vascular endothelium → endothelial disruption → binds circulating vWF → platelet aggregation + allows factor 8-vWF complex to bind endothelium → further clotting

• Infection risk: same as whole blood except minimal CMV and GVHD risk (because it has no leukocytes)
• Contains citrate to prevent clotting → risk of hypocalcemia with massive transfusion
• Indications

• Refractory heparin resistance (AT3 deficiency)
• Prolonged R-time on TEG
• TTP, HELLP
• Warfarin reversal → PCC (e.g. Kcentra) preferred for acute major bleeding

• Not indicated for

• Sole product for plasma volume expansion (use PRBC or IV fluids instead)
• Correction of mildly elevated INR (< 1.8) without signs of bleeding
• Factor deficiency when recombinant factor is available (E.g. hemophilia A → FVIII, hemophilia B → FIX)

Electroconvulsive Therapy (ECT)

• Goal: induce a seizure of at least 25 second duration

• Duration of individual seizures and cumulative seizure time correlate with clinical improvement

• Anesthetic technique

• Agents: etomidate or methohexital → succinylcholine to prevent musculoskeletal injuries
• During stimulation → initial parasympathetic response → bradycardia or asystole

• Unless pronounced and persistent, do not treat bradycardia since tachycardia will follow

• Followed by sympathetic response→ hypertension and tachycardia → esmolol or CCB boluses
• Methohexital preferred because of fewer side effects than etomidate → does not affect seizure duration

• Excitatory effects: cough, hiccups, tremors (myoclonus), twitching
• Phlebitis
• Pain on injection

• Which IV anesthetic will maximize seizure duration? Etomidate (methohexital does not affect duration)
• Airway: face mask with bite guard or LMA
• BP cuff inflated on an extremity before giving muscle relaxant → seizure can be visually monitored (since there will be no neuromuscular blockade distal to the BP cuff tourniquet)
• Medications that decrease seizures: thiopental, propofol, benzodiazepines, lidocaine, diltiazem

• Propofol can be helpful if patient has a history of seizure > 100 seconds

• Medications that increase seizures: aminophylline, caffeine, etomidate

• Physiologic effects:

• ↑ CMRO2, CBF, and ICP initially, followed by a decrease in the postictal period → contraindicated in intracranial masses
• Autonomic stimulation: initial bradycardia followed by hypertension and tachycardia → contraindicated in recent MI or stroke, and pheochromocytoma

• Very unlikely to affect pacemaker/ICD function

• Side effects: headache, myalgia, nausea, status epilepticus (though it is also used to treat this), fractures, emergence agitation, and neurocognitive impairment (long and short-term memory loss)

Fetal Heart Rate (FHR) Monitoring

• Becomes useful starting at 18-20 weeks (not useful before this)
• Normal FHR (mean over 10 minutes): 110-160
• Normal variability: peak-to-trough amplitude 6-25 bpm from baseline
• Accelerations

• Abrupt → peak in < 30 seconds
• Amplitude → >15 bpm
• Duration: 15 seconds - 2 minutes

• Decelerations

• Early: gradual (>30s), nadir coincides with contraction peak ← vagal stimulus (head compression)
• Late: gradual (>30s), nadir after uterine contraction peak ← uteroplacental insufficiency or myocardial depression due to hypoxia
• Variable: abrupt (<30s), amplitude 15 bpm, duration 15 sec - 2 min (similar to acceleration) ← umbilical cord compression

• Sinusoidal pattern → placental abruption
• Decelerations + minimal-absent variability ⇒ fetal acidosis
• Category I → normal ⇒ good

1. Baseline FHR 110-160
2. Moderate (6-25 bpm) variability
3. No late or variable decelerations
4. Early decelerations may be present
5. Accelerations may be present

• Category III → abnormal acid-base status ⇒ bad

1. Sinusoidal pattern (abruption)
2. Absent FHR variability with

• Recurrent late decelerations (gradual, nadir after contraction peak), or
• Recurrent variable decelerations (abrupt, 15 bpm, 15s-2m) ← cord compression
• Bradycardia (<110 bpm)
• If conservative treatment doesn’t work → STAT delivery

• Category II → everything that isn’t Category I or III → indeterminate clinical significance

Outcomes of Neuraxial Anesthesia

• Reduction in overall mortality
• Cardiac surgery: reduced MI, renal failure, pulmonary complications, supraventricular arrhythmia
• Major thoracic/abdominal surgery: reduced respiratory complications, opioids, improved cough

• Thoracic epidural > lumbar epidural
• Epidural local anesthetic > epidural opioid

• Bilateral total knee arthroplasty → decreased rate of blood transfusion
• Major vascular/abdominal surgery → thoracic epidural local anesthetic → decreased pain-induced sympathetic overactivity and decreased systemic opioid → decreased ileus

• No benefit with lumbar epidural infusion or thoracic epidural opioid infusion

• Fast-track laparoscopic colon resection → thoracic epidural analgesia → good pain relief but fails to speed intestinal function recovery or hospital discharge time
• Possible reduction of cancer recurrence with epidurals in prostatectomy, and rectal and ovarian cancer resection

• Volatile agents and opioids are immunosuppressants

• Source: Miller 8e Ch 56

Neuromuscular Blockade Physiology

• Normal postsynaptic nicotinic ACh-R: 2 alpha, 1 beta, 1 delta, 1 epsilon subunits

• Two ACh molecules bind each of the two alpha subunits

• Presynaptic ACh-R: 3 alpha, 2 beta → when stimulated → more ACh release (positive-feedback)

• ND-NMBAs → block this as well → “fade” and “train of four” (decreased ACh release)
• Succinylcholine does not block this → no fade or train of four (except in phase II blockade)

• Post-tetanic potentiation is due to intracellular Ca2+ accumulation during tetanus

Smoking Cessation

• Smoking →

• Decreased ciliary motility + Increased sputum production
• Nicotine → activates sensory endings → airway irritation/reactivity
• Nicotine → increased sympathetic tone → increased oxygen demand
• Carbon monoxide → 3-15% is normal in smokers (< 1.5% in nonsmokers)1

• Binds hemoglobin 240x more than oxygen → leftward shift of O2-Hgb curve
• Decreased 2,3-DPG production by RBC → leftward shift of O2-Hgb curve
• Half-life: 4-6 hours at rest, 1 hour with exercise

• Perioperative effects of smoking cessation:

• 12-24 hours: decreased CO → rightward shift of O2-Hgb curve → improved oxygen delivery
• 48-72 hours: increased secretions, more reactive airway
• 2-4 weeks: decreased secretions, less reactive airway
• 4-6 weeks: immune system and metabolism normalize
• 8-12 weeks: improved mucociliary function and small airway function
• Optimally, patients should stop smoking at least 8 weeks before surgery

• Possible benefit with quitting up to 4 weeks before
• Quitting within 4 weeks of surgery is controversial → higher complication rate

• Source: Barash 7e Ch 11

EEG-based Monitors

• Entropy: measures the amount of “disorder” → less entropy = more anesthesia; also indicates analgesia
• PSA (Patient State Analyzer): includes temporal and spatial gradients → outputs PSI (patient state index)
• BIS: bispectral (bilinear) analysis and nonlinear phase coupling of frequency pairs → outputs BIS value

• Bispectral analysis is a step up from linear power spectrum analysis

• Narcotrend: integrates data from time domain and power spectrum → outputs letters A-F (A = awake)
• Drugs that can mess with EEG-based monitoring: ketamine, nitrous oxide, dexmedetomidine

• NMDA-based drugs (ketamine and nitrous oxide) → falsely elevated BIS readingRef
• Dexmedetomidine → falsely low BIS readingRef

Carcinoid Syndrome

• Most common GI tumor → from enteroendocrine/enterochromaffin cells → produce serotonin (5-HT) → cleared by liver → no symptoms if isolated to GI tract (70%) before liver

• Only 5% of patients with carcinoid tumor present with carcinoid syndrome

• Symptomatic if metastasized to liver, or originating in lungs (20%), thyroid or ovaries
• Clinical: bronchoconstriction, episodic skin flushing, abdominal pain, diarrhea, hemodynamic instability

• Right-sided valvular disorders: TR > TS > PR > PS
• Left heart symptoms are rarely seen because of pulmonary metabolism of serotonin

• Diagnosis: 24-hour urine 5-HIAA or serum chromogranin
• Preoperatively: patients are on octreotide (IV or SQ), which suppresses serotonin release
• Carcinoid crisis: profound flushing, bronchospasm, tachycardia, and hemodynamic instability

• Life-threatening episodes that can occur with induction, tumor handling (e.g. surgery, embolization)

• Drugs to avoid in carcinoid syndrome → mostly histamine-releasing drugs and sympathomimetics

• Opioids: Meperidine and morphine
• Histamine-releasing neuromuscular relaxants: atracurium
• Exogenous catecholamines (ephedrine)
• Epinephrine, norepinephrine, dopamine, isoproterenol → release more vasoactive substances from tumors → make hypotension worse!
• Mechanical stimulation of the tumor or tumors
• Vigorous abdominal scrubbing
• The use of succinylcholine (controversial)

• Hypotension: treat with octreotide 50-300 μg IV (usually 100 μg), phenylephrine and volume
• Do not discontinue preoperative octreotide postoperatively because even though the tumor is removed, the circulating vasoactive tumor products are still active

Retrobulbar Blockade

• Local anesthetic: Lidocaine 2% (like epidural) or bupivacaine 0.75% (like spinal)
• Additive: Hyaluronidase → improves spread
• Additive: Epinephrine → reduced bleeding and prolonged block
• Complications:

• Retrobulbar hemorrhage → closing of upper eyelid, proptosis and increased IOP

• Most common significant complication

• Oculocardiac reflex stimulation → 10% decrease in HR

• More common than retrobulbar hemorrhage, but transient
• Afferent Limb: CN5 Trigeminal Nerve (V1)

• Long/short ciliary nerves → ciliary ganglion → CN V1 ophthalmic division → gasserian ganglion → CN5 sensory nucleus

• Efferent Limb: Vagus Nerve

• Visceral motor nucleus of vagus nerve (reticular formation) → efferents travel to the heart → decrease output from the sinoatrial node

• Risk factors: young age (pediatrics), light anesthesia
• Treatment:

• Deepen anesthesia (BIS < 50)
• Atropine 20 mcg/kg IV or glycopyrrolate
• Avoid remifentanil (makes it worse)

• Central retinal artery occlusion → sudden painless vision loss “shade being pulled over eye”
• Puncture of posterior globe → ocular pain and restlessness without increased IOP (vs. retrobulbar hemorrhage)
• Penetration of optic nerve
• Inadvertent brainstem anesthesia → disorientation, aphasia, hemiplegia, respiratory depression
• Epinephrine toxicity

• Optic cone: four rectus muscles, connective tissue that extends back to include the optic foramen
• Goal: analgesia and eye akinesia
• Retrobulbar block: injection into optic cone → near optic artery and nerve
• Peribulbar block: injection outside optic cone → farther from optic artery and nerve → theoretically safer

• However larger amount of anesthetic needs to be injected → increased risk of high IOP
• Time to onset longer than retrobulbar block
• Lower incidence of complete akinesia (complete akinesia is desirable for surgery)

Fenoldopam

• Selective DA1 agonist with no α/β, or DA2 activity (vs. dopamine) → potent direct renal vasodilator
• Uses (studies are equivocal on its efficacy so far)

• Hypertension: can drop the BP while leaving renal blood flow intact (unlike sodium nitroprusside)

• Increases GFR → increases diuresis and natriuresis

• Cardiac surgery and AAA repair: antihypertensive and renal protective effects

• But in high-doses: causes tachycardia, limiting its usefulness

• Fast onset (5 minutes) and fast offset (elimination half-life of 5 minutes)
• Can cause increased IOP → avoid in glaucoma

Biostatistics: Statistical Tests

• Standard Error of the Mean (SEM) = Standard deviation (σ) ÷ √n

• Two groups can have same mean and SD but different SEM if sample size is different

• Standard deviations: 1σ = 68%, 2σ = 95%, 3σ = 99.7%
• Example data demonstrating the variable types

• Discrete: current smoker (yes/no)
• Continuous: age, BMI, hemoglobin level
• Survival (events): # of people with stage 4 breast cancer who survived at 1y, 2y, 3y, 4y and 5y
• Ordinal: pain scale (0-10)

• T-test: paired vs. unpaired

• Paired: e.g. same subject before and after intervention
• Unpaired: e.g. two groups of subjects → one group gets an intervention, one doesn’t

• Z-score → number of standard deviations away from the mean

• A z-score of +2 indicates 2 SD above the mean → 97.7% of values fall below this

Axillary Block

• Excellent anesthesia for structures distal to elbow
• Axillary sheath contains: radial, ulnar, median n.
• Musculocutaneous nerve (MCN) branches off proximal to where the block is performed → lateral forearm sensation

• Travels outside axillary sheath, between biceps and coracobrachialis muscle
• Inject local into coracobrachialis muscle
• Needs to be blocked separately from axillary sheath

Crystalloids: Composition

• LR has 4 K+, 3 Ca2+ and 28 lactate → lactate ion is hepatically metabolized into bicarbonate

• LR has the least sodium → lowest osmolarity (among the isotonic “balanced” solutions)

• NS has SID of 0 → makes it acidic (reminder: SID < 40 = acidic) → causes metabolic acidosis
• Plasma-Lyte has no calcium (vs. LR) and is the only crystalloid that has 3 Mg2+
• Grouped by content

• Potassium-containing fluids: LR, Plasma-Lyte
• Calcium-containing fluids: LR
• Magnesium-containing fluids: Plasma Lyte
• Buffers: LR uses lactate, Plasmalyte uses acetate and gluconate

• Source: Miller 8e

Lambert-Eaton Myasthenic Syndrome (LEMS)

• Neoplastic syndrome of antibody-mediated destruction of presynaptic voltage-gated Ca channels → decreased ACh release

• Not reversed by anticholinesterase drugs (there’s not enough ACh to begin with)
• Generally associated with lung carcinoma (especially small cell lung carcinoma)

• Affects proximal limbs (legs > arms) → weakness improves with repetition
• NMBAs: more sensitive to both depolarizing and nondepolarizing NMBAs

Bronchial Blocker

• Situations when the use of a bronchial blocker is advantageous (vs. double-lumen tube [DLT])

• Postoperative mechanical ventilation: if you use a DLT → you have to swap it out at the end of surgery for a single-lumen tube → may be complicated with edematous airway after surgery

• If SLT + bronchial blocker is used → no need to change the SLT → no airway compromise

• Difficult airway (poor visualization, previous ENT surgery) → single-lumen tube → bronchial blocker
• Selective lobar blockade (e.g. in a patient with previous contralateral pulmonary resection)

• Complications and disadvantages of bronchial blockers

• More prone to dislodgement → inability to ventilate
• Failure to achieve lung separation because of abnormal anatomy
• Lack of a seal within the bronchus
• Inclusion of the bronchial blocker or the distal wire loop into the staple line during lobectomy

• Bronchial blocker needs to be withdrawn a few centimeters before stapling!

• Source: Miller 8e Ch 66

Airway Exam

• Non-reassuring findings (ASA Practice Guidelines)

• Teeth:

• Long incisors
• Prominent “overbite”
• Patient cannot bring mandibular incisors anterior to maxillary incisors

• Mouth

• Less than 3 cm interincisor distance (mouth opening)
• Mallampati: Uvula is not visible when tongue is protruded with patient in sitting position
• Highly arched or very narrow palate
• Mandibular space that is stiff, indurated or occupied by a mass

• Neck:

• Less than three ordinary finger breadth thyromental distance
• Short neck length
• Thick neck circumference
• Decreased extension or flexion of the neck

• Predictor of both difficult intubation and ventilation

• Mallampati-Samsoon class III or IV
• Thyromental distance < 6 cm (Kheterpal 2006)

• Predictors of difficult face mask ventilation (Miller 8e Box 55-2 & Barash 8e Table 28-8)

• Beard (both)
• Male gender (Barash)
• OSA (Miller) or history of snoring (Barash)
• Age > 57y (Miller) or >55y (Barash)
• BMI > 30 (Miller) or >26 (Barash)
• Edentulousness (both)
• Limited jaw (mandibular) protrusion and snoring (Kheterpal 2006)

• Predictors of difficult intubation

• History of difficult intubation
• Protruding upper incisors, mouth opening <3 cm, small mandibular space
• Failed TMJ translation
• Limited neck ROM
• TMD <6 cm
• Short thick neck

• Mallampati classification

• Correct position: seated in neutral position, mouth opened as wide as possible, tongue protruded as far as possible. No phonation (raises soft palate and allows visualization of additional structures)
• Class I — soft palate, fauces, uvula, pillars
• Class II — soft palate, fauces, uvula (no pillars)
• Class III — soft palate, base of the uvula (no fauces)
• Class IV — soft palate not visible (only hard palate is visible)

• Source: ASA Practice Guidelines for Management of the Difficult Airway (2013), Benumof and Hagberg’s Airway Management 3e Ch 9, Kheterpal et al. Anesthesiology. 105(5):885-891

Airway Innervation

• Larynx motor (vagus): recurrent laryngeal nerve except cricothyroid muscle (external branch of SLN)
• Sensory:

• Glossopharyngeal nerve: posterior third of the tongue, vallecula, anterior surface of the epiglottis, posterior and lateral walls of the pharynx → afferent pathway of the gag reflex
• Superior laryngeal nerve internal branch → lower pharynx, upper part of the larynx (including the glottic surface of the epiglottis and the aryepiglottic folds), rostral surface of the vocal cords
• Vocal cords and below: recurrent laryngeal nerve (RLN)

• Blocked by transtracheal injection of local anesthetic
• Left RLN can be damaged during PDA repair

• Internal branch of SLN and RLN are not strictly separated → some interconnections exist

• For awake fiberoptic intubation, need to block (3): glossopharyngeal, internal branch of SLN, and RLN

• Internal branch of SLN → block inferior and deep to the greater cornu of the hyoid bone
• External branch of SLN → block at superior cornu of the thyroid cartilage

• Source: Hagberg and Benumof's Airway Management 4e Ch 12

Postpartum Hemorrhage

• Definition: >500mL vaginal delivery, >1,000 mL cesarean delivery, or >10% drop in hematocrit
• Uterine Atony (most common cause of postpartum hemorrhage)

• Risk factors:

• Cesarean section
• Oxytocin infusion for labor and prolonged labor (weakened uterus)
• High parity (weakened uterus)
• Overdistended uterus (multiple gestations, polyhydramnios)
• Abnormal or retained placenta

• Treatments

• Oxytocin → Gq receptor → increased intracellular Ca2+ → uterine contraction

• Similar to ADH → fluid retention → volume overload sensed by atria → ANP release → natriuresis (hyponatremia) and diuresis
• Dosing: 20-40 units in 1 L crystalloid IV drip
• Hypotension, arrhythmias, nausea, headache

• Carboprost (Hemabate) → 15-methyl-PGF2ɑ → increases force and frequency of contractions

• Dosing: 250 mcg intramuscular every 15-90 minutes, up to 8 times
• Bronchoconstriction → avoid in asthma
• Nausea, diarrhea, pulmonary hypertension

• Misoprostol → PGE1 analogue

• Dosing: 200 mg PO or per rectum

• Methergine → partial agonist at ɑ1-adrenergic, dopamine, and 5-HT → increases intracellular Ca2+ levels → increases uterine (and smooth muscle) contractions and tone

• Dosing: 0.2 mg intramuscular
• Hypertension → avoid in preeclampsia, HTN, CAD
• Vasospasm → avoid in CAD; avoid with protease inhibitors (CYP34A inhibitor)
• Pulmonary hypertension, edema

• Vasopressin → can be injected directly intrauterine → direct constriction

• Placenta accreta

• Accreta vera: abnormal adhesion of placenta to myometrium (no invasion) without decidual line

• Risk factors: prior uterine surgery, placenta previa, multiparity, old mom (>35y), smoking

• Increta: invasion of myometrium
• Percreta: invasion through myometrium → breaches uterine wall → can invade other organs

• Surgical options: intrauterine balloon, B-Lynch sutures, hysterectomy
• Prophylaxis: balloon occlusion or embolization of internal iliac arteries

Scopolamine for PONV Prophylaxis

• Mechanism: centrally acting anticholinergic agent that with a relatively short half-life

• Antagonizes M1 receptors (and some H1 receptors) in the cortex, area postrema, pons, hypothalamus

• Transdermal formulation → longer duration of action, up to 72 hours (usual dose 1.5 mg patch over 72 hours)

• Peak plasma concentration at 12-24 hours after administration
• Patch should not be cut to limit the dose administered

• Timing of application: Transdermal scopolamine appears to be similarly effective when applied the night before the surgical procedure or the morning of the surgical procedure (RRs = 0.56 and 0.61, respectively)
• Adverse effects

• Visual disturbances (blurry vision) at 24-48 hours postoperatively
• Can cause temporary pupil dilation → use with caution in neurosurgery (where pupil dilation can be a marker of serious complications), avoid in closed angle glaucoma

• Treatment for scopolamine toxicity: physostigmine (crosses BBB)
• Source: Miller 8e Ch 97

Neuropathic Pain

• Umbrella term for: diabetic neuropathy, CRPS, postherpetic neuralgia, multiple sclerosis
• Symptoms: intermittent pain, hyperpathia (painful stimuli → exaggerated pain), burning pain
• Treatment options:

• Antidepressants (TCAs, SSRIs) and anticonvulsants (carbamazepine, gabapentin, pregabalin)
• Methadone → due to its NMDA-antagonist properties
• Tramadol → due to its serotonin and norepinephrine reuptake inhibition (also a mu-opioid agonist)
• Steroids are not effective for chronic neuropathic pain (beneficial in acute herpes zoster)

Diuretics

• HCTZ (thiazides) → blocks Nain/Clin cotransporter in the distal convoluted tubule

• Inhibition of Na+ resorption → hyponatremia
• Increased Cl- excretion → hypochloremic metabolic alkalosis
• Increased K+ excretion → hypokalemia
• Inhibit Ca2+ excretion → hypercalcemia

• Furosemide → blocks Nain/Kin/Clin channels in ascending loop of Henle → decreased Na+ and Cl- absorption

• Increased K- and Cl- excretion → hypochloremic hypokalemic metabolic alkalosis
• Volume contraction → constant HCO3- → contraction alkalosis
• Other loop diuretics: Bumetanide, Ethacrynic acid, Torsemide

• Potassium-sparing diuretics

• Spironolactone → Blocks aldosterone receptors in distal convoluted tubule
• Triamterene → Blocks ENaC → Na+ and water are diuresed, K+ is spared
• Amiloride → Blocks ENaC → Na+ and water are diuresed, K+ is spared

Pediatric PONV

• Risk factors → pediatric PONV (most studies look at vomiting only) is twice as common as adult PONV

• Age > 3 years
• Duration > 30 min
• Surgery type (strabismus repair)
• Patient or family history of PONV

• Gender: same risk between males and females until puberty → then, females are more likely to have PONV
• Treatment

• Ondansetron (NNT = 3) 0.1-0.15 mg/kg
• Dexamethasone (NNT = 4) 0.15 mg/kg
• Droperidol (NNT = 5) 10-15 mg/kg

Epidural: Paramedian Approach

• Skin → subcutaneous tissues → muscle → ligamentum flavum → epidural space → dura → arachnoid

• No interspinous or supraspinous ligaments contacted in this approach

• Source: Morgan & Mikhail 5e Ch 45 - Figure 45-14

Nitrous Oxide

• least soluble, fastest acting inhaled anaesthetic agent available → MAC 105%
• NMDA antagonist: main mechanism of anesthetic activity (plus ɑ-adrenergic, dopaminergic; minimal GABA)
• Pregnancy: no uterine relaxation → but some concern about B12 inactivation and developing fetus
• Nitrous oxide: vasodilation (↑ CBF) + increase in CMRO2 (↑ CBF) → ↑↑ CBF → ↑↑ ICP
• N2O MACawake is 0.55–0.6 MAC → other agents MACawake is 0.35 MAC → faster emergence
• Blue tank: 750 psig, 1590 L, pressure won’t drop till tank reaches about 250 L (16%)
• Adverse effects:

• Megaloblastic changes and agranulocytosis → N2O irreversibly oxidizes cobalt atom of Vitamin B12 → decreased activity of B12-dependent enzymes

• 70% N2O → 46 minutes → 50% inactivation of methionine synthetase
• 24 hours of exposure → megaloblastic changes
• 4 days of exposure → agranulocytosis
• Kids with MTHFR gene defects → can be more susceptible to this adverse effect

• Increased homocysteine levels → possible (data is equivocal) increased MI and stroke risk

• ENIGMA-II trial: >2 hours of N2O → increased risk of MI (OR 95% CI 1.01-2.5)
• POISE trial: no increase in rates of death, MI or stroke

• Potential bowel distension → data regarding obscuring of laparoscopy view is equivocal
• Pulmonary vasoconstriction → avoid in pulmonary hypertension

• Avoid in pneumocephalus, pneumothorax, air embolism
• Eye surgery

• Surgeon injects intravitreal air bubble to tamponade retina against the wall of the globe
• Sulfur hexafluoride → poorly soluble gas used to prolong the resorption of intravitreal air bubbles → nitrous oxide diffuses and causes bubble expansion → potential for dangerous increases in IOP

• Shut off nitrous oxide 15 minutes before placing bubble → avoid nitrous oxide for 7-10 days after

• Perfluoropropane → persists longer, for weeks → nitrous oxide should be avoided for >1 month

• Source: Miller 8e Ch 26, Miller 8e Ch 84, ESA Task Force on N2O Report (2019)

Periodic Paralysis Syndromes

• Hyperkalemic periodic paralysis

• Very frequent attacks (hyper)
• Causes of attacks: rest after exercise, fasting, stress, hypothermia, ingesting small amount of K

• Fasting → glucagon release → hyperkalemia

• Treatments: acetazolamide (unknown mechanism), β-agonists, K+-wasting diuretics, insulin

• Hypokalemic periodic paralysis → most common type of periodic paralysis

• Infrequent attacks
• Causes of attacks: exercise, carbohydrate loading (e.g. D5 in IVF), stress, hypothermia

• Carb load → insulin release → ↑ Na-K ATPase activity → K+ into cells → ↓ serum K+

• Treatments: acetazolamide (also works for hyperKPP), potassium-sparing diuretics
• Intraoperative considerations: monitor [K+], avoid high Glc, insulin, sodium, minimize catecholamine release and temperature changes, post-op meals low in carbs and sodium

Cardiopulmonary Changes in Pregnancy

• Cardiovascular

• SVR decreases 20% → MAP decreases (diastolic > systolic → widened pulse pressure)

• Progesterone → vasodilation → ↓SVR
• Hemodilution → less viscosity → ↓SVR
• Low resistance uteroplacental vascular bed in parallel → ↓SVR

• SV increases 30% + HR increases 20% → CO increases 50%

• CO plateaus in 3rd trimester; ↑↑ more in labor; ↑↑↑ most immediately postpartum [150%])

• CVP and PCWP are unchanged

• Pulmonary

• RR increases (then plateaus), TV increases 50% → MV increases 50% → respiratory alkalosis

• PaCO2 = 30 mmHg in pregnancy, PaO2 increases, HCO3 decreases, BE decreases
• IRV is slightly increased

• ERV and RV decrease → FRC decreases
• VC is unchanged, TLC slight decrease (5%)
• Oxygen consumption: increased 20-40%

• Oxygen consumption (in unmedicated patient): ↑ 40% in first stage of labor, ↑↑ 75% in the second stage of labor (hyperventilation, pushing, ↑ uterine contractility)

• Apnea time → decreases due to (1) decreased FRC and (2) increased oxygen consumption

Hematological Changes in Pregnancy

• Changes in CBC

• RBC volume increases 25%
• Plasma volume increases 50% → physiological anemia of pregnancy (around 11 g/dL)
• Increased WBC and neutrophils
• Decreased platelets

• CMP: Decrease in albumin and total protein → decreased colloid pressure

• Increase in total amount of serum alpha and beta globulins → albumin:globulin ratio decreases

• Changes in iron stores

• Decrease in ferritin, serum iron, percentage saturation of transferrin
• Increase in transferrin and TIBC

• Changes in coagulation

• Hypercoagulable state → 20% decrease in PT and aPTT
• Increased factor I (fibrinogen) and factor VII
• Decreased factor XI, XIII, ATIII, and Protein S
• Unchanged factor II and factor V, Protein C
• Fibrinogen increased → ↑ fibrin split products (D-dimer - less sensitive for PE in pregnancy)

• Oxygen-hemoglobin dissociation curve

• Normal P50: 26.8
• Maternal hemoglobin P50: 30 ⇒ rightward-shift → better oxygen delivery to the fetus

• Pregnancy → respiratory alkalosis → you would expect leftward shift… but:
• Increased 2,3-BPG production → rightward-shift

• Fetal hemoglobin P50: 19 → more affinity for oxygen

• Fetal hemoglobin does not bind 2,3-BPG

• Double Bohr effect: in the placenta

• CO2 diffuses from fetal to maternal side → decreased maternal Hb oxygen affinity
• Relative decrease in CO2 on the fetal side → increased fetal Hb oxygen affinity

Anesthetic Management of the Brain-Dead Organ Donor

• Physiologic changes

• Catecholamine storm → a response to maintain CPP → ICP increased

• Initially increases blood volume and cardiac output + cytokines → pulmonary edema

• Myocyte necrosis → ischemic changes on ECG
• Hyperglycemia from catecholamines, steroid supplements, decreased insulin levels
• Diabetes insipidus from posterior pituitary ischemia → Hypernatremia + Polyuria        

• Vasopressin infusion can replace this deficiency and improve hemodynamics

• Cardiovascular

• Use crystalloid to maintain MAP 60-100 mmHg and CVP 4-10 mmHg
• Vasoactive drugs: dopamine, vasopressin (first choice for potential heart donors)

• Large doses of norepinephrine can cause cardiac graft dysfunction
• Goal: Low vasopressor use (≤1 pressor and low dose)

• Lungs

• Fluid restriction increases the number of lung grafts available for transplantation
• Low tidal volume (6-8 mL/kg), low FiO2, high PEEP, recruitment maneuvers
• Terminal PaO2 >100 mmHg or >80mmHg on FiO2 ≤ 40%
• Aerosolized terbutaline increases alveolar fluid clearance via β-adrenergic stimulation
• Suctioning and bronchoscopy can be performed to remove mucous plugs

• Temperature: maintain ≥ 35°C
• Exogenous vasopressin, thyroid hormone replacement and methylprednisolone (steroid) are beneficial
• Target glucose level: 120-180 mg/dL
• Normal electrolytes: Na < 150
• Source: Miller 8e Ch 75

Neuromuscular Blocking Drugs (NMBD): Drug Interactions

• Among nondepolarizing muscle blockers

• Additive: when the effect is the sum of equipotent doses of either drug given alone

• Happens with chemically related agents such as roc+vec or cis+atra

• Synergistic: when the effect of the mixture is greater than the equipotent dose of either drug

• Happens with structurally dissimilar agents (e.g. rocuronium + cisatracurium)

• Depolarizing and nondepolarizing muscle blockers

• SCh before NMBD: conflicting results

• Potentiation of dTc, pancuronium, vecuronium, and atracurium by previous administration of SCh

• Small doses of nondepolarizing agents before SCh: antagonistic effect → need more SCh

• Inhaled Anesthetics: potentiates the neuromuscular blocking effect of NMBD

• Decrease in the dosage requirement of the neuromuscular blocker and prolongation of both the duration of action of the relaxant and recovery from neuromuscular blockade.
• Magnitude of potentiation depends on

• Duration and dose
• Des > Sevo > Iso > Halo > nitrous oxide, barbiturate, opioid, propofol anesthesia

• Antibiotics

• Aminoglycosides, polymyxins, lincomycin, and clindamycin

• Inhibit prejunctional release of ACh and depress postjunctional nAChR sensitivity to ACh

• Tetracyclines only depress postjunctional nAChR sensitivity to acetylcholine
• Cephalosporins and penicillins (e.g. ampicillin) do not affect neuromuscular blockade

• Magnesium: potentiates neuromuscular blockade

• Inhibit presynaptic Ca2+ channels → less ACh release
• Inhibitory effect on postjunctional potentials → decreased excitability of muscle fiber membranes
• Succinylcholine: controversial, but mostly antagonizes succinylcholine

• Calcium: Ca2+ triggers ACh release → antagonizes neuromuscular blockade

• Higher doses of NMBA may need to be given in hypercalcemia (e.g. hyperparathyroidism)

• Lithium → activates K+ channels → inhibits presynaptic transmission and postsynaptic contraction

• Synergistic with nondepolarizing agents, additive with succinylcholine

• Local Anesthetics: dose-dependent potentiation of neuromuscular blocking agents
• Antiarrhythmics: Quinidine potentiates the neuromuscular block at the prejunctional membrane
• Antiepileptic Drugs (e.g. phenytoin, carbamazepine)

• Acute use: potentiation of NMBA action
• Chronic use: Resistance to aminosteroid ND-NMBAs
• Slight prolongation of succinylcholine action in patients taking anticonvulsants (clinically negligible)

• Diuretics

• Furosemide: effect is controversial
• Acetazolamide: antagonize the effects of anticholinesterases

• Dantrolene: enhances nondepolarizing
• Donepezil (CNS AChE inhibitor used in Alzheimer’s) may prolong duration of succinylcholine Ref

• Only a weak inhibitor of PChE
• May cause resistance to non-depolarizing NMBA

• Azathioprine: minor antagonistic action on muscle relaxant-induced neuromuscular blockade
• Anti Estrogenic drugs (Tamoxifen): potentiate the effects of nondepolarizing neuromuscular blockers.
• Steroids: antagonize the effects of nondepolarizing neuromuscular blockers + increased myopathy risk
• Enhancers: Inhaled anesthetics, magnesium, antibiotics, lithium, small-dose local anesthetics, antiarrhythmics (quinidine), acetazolamide (antagonizes neostigmine), dantrolene, tamoxifen, acute antiepileptics
• Antagonists: calcium, chronic antiepileptics, steroids, large IV dose local anesthetics, azathioprine

• Sources: ABA Content Outline I.A.5.e.8, Miller 8e Ch 34, Meyler's 7e 615-641, Barash 8e Ch 21

Near Drowning Resuscitation

• Modified BLS: start with rescue breaths (not compressions) → then proceed to chest compressions

• Classic A-B-C (airway, breathing, circulation) approach is recommended in instances where poor oxygenation/ventilation is the root cause (e.g., drowning, suffocation, asphyxiation) and in LAST
• Compressions will not be as helpful because there is no oxygen to circulate vs. in cardiac arrest, the lungs have some residual oxygen content to allow oxygen delivery

• Do not perform the Heimlich maneuver or abdominal thrusts to try and relieve aspiration

• Only suctioning is safe and recommended

• Do not perform cervical spine immobilization: low incidence of C-spine injury → can impede airway access
• High incidence of pulmonary complications, electrolyte derangements, and hypothermia 
• Poor prognostic indicators:

• Prolonged immersion (> 5 minutes)
• Delayed initiation of CPR (> 10 minutes)
• Fixed/dilated pupils, GCS < 6, abnormal brain CT within 36h, No purposeful movements within 48h

• Source: 2015 AHA CPR Guidelines Part 10.15

Hypoxic Pulmonary Vasoconstriction (HPV)

• Pulmonary vascular response to a low alveolar oxygen partial pressure (PAO2) → precapillary vasoconstriction

• PVO2 is a much weaker stimulus
• Mechanism: hypoxia → inhibits outward flow from voltage-gated K+ channels in mitochondria → depolarization → Ca2+ entry → increased intracellular Ca2+→ contraction
• Biphasic response (both onset and offset)

• Rapid-onset phase: plateau in 20-30 minutes
• Delayed phase: starts at 40 minutes and plateaus after several hours

• Drugs that augment (improve) HPV

• Catecholamines: adrenaline, dopamine, dobutamine, dopexamine, and isoprenaline
• Inhaled β2-agonists at clinically relevant doses do not inhibit HPV and may potentiate it
• α1 agonists: norepinephrine or phenylephrine, both of which cause pulmonary vasoconstriction

• Inhibitors of HPV (either vasodilation or increased pressure against which the vessel must constrict)

• Vasodilators: ACE Inhibitors, hydralazine, calcium-channel blockers (verapamil, nifedipine), SNP, NTG
• Acetazolamide (direct effect on pulmonary smooth muscle cells)
• Inhaled nitric oxide (NO), inhaled PDE5 inhibitors, inhaled prostacyclins
• Hypocapnia → vasodilation
• Endothelin antagonists (bosentan)
• Modern volatile anesthetic agents inhibit HPV in a dose-dependent manner

• Unlike other volatile anesthetics, nitrous oxide is not a vasodilator and seems to have pulmonary vasoconstrictive properties → but probably inhibits HPV
• But under 1 MAC, no benefit to using TIVA vs. volatiles for one-lung ventilation

• Clinical conditions that can inhibit HPV: increased pressure (PPA) against which the vessels must constrict

• Mitral stenosis
• Volume overload
• Thromboembolism
• Hypothermia

• Do not affect HPV

• Propofol and opioids
• Thoracic epidural sympathetic blockade

• Sources: Kaplan’s Cardiac Anesthesia 7e Ch 49 & Ch 36, Miller 8e Ch 66, Murray and Nadel's Respiratory Medicine 6e Ch 59

Acromegaly

• Anterior pituitary adenoma → excess GH
• Mass effects of pituitary tumor: headache, visual field defects
• Hypertrophy of skeletal, connective, and soft tissues → large tongue and epiglottis → upper airway obstruction

• Incidence of difficult intubation: 20% to 30%
• Osteoarthritis, osteoporosis, skeletal muscle weakness
• Increased lung volumes

• Thickening of the vocal cords or paralysis of an RLN due to stretching → hoarseness
• Subglottic narrowing → Dyspnea or stridor
• Peripheral nerve or artery entrapment, hypertension, and DM
• Diagnosis: IGF-1 is a sensitive, screening test → lack of GH suppression after oral glucose load is specific

Myasthenia Gravis (MG)

• Autoimmune disorder → antibodies against motor endplate ACh-receptor
• Affects bulbar and ocular muscles first → strength gets worse with repetition
• Treatment: pyridostigmine (anticholinesterase), corticosteroids, IVIG, thymectomy
• Anesthetic Considerations

• Resistance to succinylcholine → 2-3x higher dose → higher risk of phase II blockade
• Very sensitive to nondepolarizing NMBAs
• Generally NMBAs avoided, but now sugammadex is a viable option
• Regional anesthesia: amides are preferred because esters are metabolized by cholinesterases which are inhibited by pyridostigmine (MG treatment)
• Risk factors for postoperative myasthenic crisis and ventilatory support:

• Prolonged duration of disease (>6y)
• Presence of previous respiratory problems, bulbar symptoms, or coexisting lung disease
• pyridostigmine doses >750 mg/day
• Preoperative FVC < 2.9 L 
• Serum antiacetylcholine receptor antibody >100 nmol/L 

• Pregnancy: MG worsens in last trimester and postpartum
• Neonatal myasthenia gravis

• Infants of MG mothers (10-20%) can have transient neonatal myasthenia gravis for up to 3 weeks from transferred maternal antibodies → resolves on its own → may need supportive care

• Source: Miller 8e Ch 42

Tumescent Anesthesia

• Tumescent = swollen
• Technique: inject large amount of saline + lidocaine (0.05%) + epinephrine solution → liposuction
• Maximum dosage for tumescent lidocaine is 35-55 mg/kg (vs. 4.5 mg/kg or 300 mg for local lidocaine)

• Concentration peaks 8-12 hours after injection → be cautious if injecting more local anesthetics

• Maximum dosage for tumescent epinephrine: 0.055 mg/kg (1:1,000,000 [million] concentration)
• Lidocaine is metabolized by hepatic CYP3A4 → increased risk of toxicity with CYP3A4 inhibitors
• Cardiac risks: fluid overload, pulmonary edema, cardiac arrest (high local concentration + sedatives)
• Caution with IV or inhaled anesthesia during tumescent anesthesia: can mask local anesthetic toxicity

Amiodarone

• Mechanism of Action: mainly blocks K+ channels (Class III), also Na (Class I), β (Class II), Ca (Class IV)
• Uses: refractory ventricular arrhythmias, sustained SVT, atrial flutter/fibrillation especially with CHF
• Contraindications: preexisting bradycardia or heart block, avoid in pregnancy (Class D)
• Side effects:

• Cardiovascular: hypotension and bradycardia at high-doses, QT-prolongation
• Thyroid: hypothyroidism (20%) or hyperthyroidism (more rare; can worsen heart failure)
• Lung: pulmonary toxicity dependent on cumulative dose (long half-life of 45 days!)
• Eyes: reversible corneal microdeposits, which can occasionally interfere with vision
• Nerves: peripheral neuropathies
• Liver: elevated AST/ALT, LDH
• Skin: sensitivity to light, bluish pigmentation of the skin

• Source: Meyler's Side Effects of Drugs 16e p. 255-289

QT Prolongation

• Normal QTc is less than 450 ms in males and 470 ms in females
• Congenital Long QT Syndrome (LQTS): defects in cardiac sodium or potassium channels

• With deafness ⇒ Jervell and Lange-Nielsen syndrome
• Without deafness ⇒ Romano-Ward syndrome

• Arrhythmias triggered by adrenergic stimulation → treat with β-blockers
• Pathophysiology of dangerous arrhythmias: afterdepolarizations → reentrant ventricular arrhythmias
• Treatment:

• Acute: replace Mg, K, Ca, avoid amiodarone
• Maintenance: β-blockers

• If refractory: cardiac pacing, AICD, left stellate ganglion sympathectomy

• Common anesthetic drugs that prolong QT: amiodarone, haldol, droperidol, clarithromycin, erythromycin, ondansetron, methadone, glycopyrrolate, volatile anesthetics (dose-dependent)
• MNEMONIC: "hyPeR" ⇒ hyPeR-kalemia/-calcemia/-magnesemia lead to PRolongation of the PR interval and the opposite (shortening) with the QT interval

Laser Surgery Considerations

• Flammability of ETT materials: Polyvinyl chloride (PVC) > Red rubber > Silicone

• None of the three (PVC, red rubber, silicone) are safe when exposed to Nd:YAG laser

• Laser-Resistant Tracheal Tubes: two types

• Metal tubes (stainless steel) or
• Nonmetal tube core with a metallic overlay (aluminum or copper)
• Cuffs: unprotected and prone to ignition → some tubes have double cuffs to enhance safety

• Consider filling cuff with methylene blue (indicator) or saline (decrease ignition risk)

• Eye injury is also a concern with lasers → eye protection depends on laser

• CO2 → any clear glass, including regular eyeglasses
• Nd-YAG beams → special green-tinted goggles
• Argon → amber-orange filter
• KTP beams → red filter

• Source: Miller 8e Ch 88

Mandibular Hypoplasia

• Constricted mandibular space → posterior prolapse of the tongue → airway compromise
• Associated syndromes:

• Pierre Robin Sequence: triad of micrognathia, glossoptosis, airway obstruction ± cleft palate

• Glossoptosis = posterior displacement of the tongue
• Associated with some syndromes: Stickler, velocardiofacial, and Treacher-Collins
• Airway management: avoid paralytics, maintain spontaneous respiratory, maximize FiO2

• Hemifacial Microsomia: second most common congenital facial anomaly (after cleft lip/palate)

• Facial asymmetry disorder → unilaterally affects the lower half of the face → prominent hypoplasia of malar-maxillary-mandibular complex
• Goldenhar syndrome (oculoauriculovertebral syndrome) most severe form of syndromic hemifacial microsomia: colobomas + vertebral anomalies

• Treacher-Collins Syndrome (mandibulofacial dysostosis) → defective bone formation → hypoplasia of supraorbital rims, zygoma, mid facial bones, mandible, ear deformities, cleft palate

• Source: Stoelting’s 5e Ch 27

Emergence Excitement

• Unlike delirium, emergence excitement typically resolves quickly and is followed by an uneventful recovery
• Transient confusional state during emergence from anesthesia → common in kids (>30%) peak age 2-4 years

• Most frequently associated with rapid “wake up” from sevoflurane and desflurane → propofol results in a significantly smoother awakening than sevoflurane, despite rapid emergence
• Prevention: reduce preoperative anxiety, treat postoperative pain, stress-free recovery environment
• Medications to prevent/treat: midazolam, clonidine, dexmedetomidine, fentanyl, ketorolac, physostigmine

• Less common in adults (5%)

• Risk factors: premedication with midazolam, breast surgery, abdominal surgery

• Source: Miller 8e Ch 96

Hepatic Blood Flow Regulation

• Receives 25-30% of cardiac output
• Inputs: hepatic artery and portal vein

• 75% flow from portal vein, 25% from hepatic artery (but each supplies 50% of O2 content)
• Postprandial: more from the portal vein
• Hepatic artery: responds to hepatic metabolic demand → autoregulation → compensatory ↑ hepatic artery blood flow when ↓ portal vein flow ⇒ “hepatic arterial buffer response”

• Mechanism: portal vein flow decreases → adenosine release → A2 receptor → vasodilator → hepatic artery vasodilation → increased hepatic blood flow
• β2-adrenergic receptors (not on portal vein) → hepatic artery vasodilation → ↑ hepatic flow

• Propranolol blocks this → ↓ hepatic blood flow

• ɑ-adrenergic receptors: decrease both portal vein and hepatic artery blood flow → attenuates hepatic arterial buffer response

• Example: septic shock → norepinephrine drip → splanchnic hypoperfusion

• Decreases in PO2 (hypoxia) or pH (acidosis) of portal venous blood → increases in hepatic arterial flow
• General anesthesia → ↓ BP → ↓ portal blood flow → ↑ hepatic arterial flow

• Volatile anesthetic decreases this arterial response in a dose-related fashion

• Angiotensin II → constricts the hepatic arterial and portal venous beds → decreased flow
• Vasopressin → splanchnic vasoconstriction, but lowers portal venous resistance → may treat portal hypertension
• D1 receptor and glucagon: increase hepatic blood flow 

• Glucagon is trying to raise glucose through liver gluconeogenesis → more hepatic blood flow

• PEEP: increased hepatic venous pressure + decreased CO → ↓ hepatic blood flow
• Sources: Miller 8e Ch 22, Barash 7e Ch 45

Organophosphate Poisoning

• Pathophysiology: absorbed through skin/mucous membranes → anticholinesterase toxicity → ↑ ACh
• Clinical

• Mild: headache, miosis, rhinorrhea, salivation
• Moderate: severe rhinorrhea, dyspnea, fasciculations
• Severe: respiratory difficulty, urinary incontinence, weakness, paralysis, convulsions

• Treatment

• First step: termination of exposure → remove contaminated clothing, move away from source

• “Wet” decontamination → wash with copious amounts of water and 0.5% hypochlorite

• Atropine 2-4 mg IV → competitive muscarinic ACh antagonist
• Pralidoxime → reactivates AChE by removing organophosphate → administer ASAP → as time passes, the organophosphate bond to AChE “ages” and becomes harder to reverse

AV Node Perfusion

• PDA branches off of RCA in 85% of people ⇒ “right-dominant”

• Supplies posterior ⅓ of interventricular septum and posteromedial papillary muscle
• RCA → PDA → supplies AV nodal artery → RCA ischemia causes complete heart block

• AV Nodal artery supplied by RCA 90% of the time (LCx 10% of the time)

• “Left-dominant” ⇒ left circumflex gives rise to PDA
• Dual supply of PDA from RCA and LCx ⇒ “co-dominant”
• RCA ischemia → inferior wall of LV, lateral and posterior walls of RV

• Use nitroglycerin and morphine with caution in inferior wall MI → ↓ preload → hypotension

Porphyria

• Disorder of heme synthesis pathway → toxic intermediates accumulate → neurotoxic
• Acute porphyria clinical features: neurotoxicity (CNS, peripheral, and GI) →

• Autonomic instability: fever, tachycardia, weakness, seizures, confusion, hallucinations
• GI neuropathy: nausea, emesis, abdominal pain

• Many types exist → important ones in anesthesia: AIP, variegate porphyria, hereditary coproporphyria

• Acute intermittent porphyria (AIP)

• Porphobilinogen deaminase deficiency → δ-aminolevulinic acid (D-ALA) accumulates
• No skin lesions
• Acute treatment: IV human hemin solution that inhibits 5-aminolevulinic acid synthase

• Variegate porphyria → neurotoxicity + skin lesions
• Hereditary coproporphyria → neurotoxicity + occasional skin lesions → least severe of the three

• Drugs to avoid (triggers of acute porphyria)

• Common ones from Barash & Miller: barbiturates (methohexital), benzodiazepines, ketamine, etomidate
• Some additional ones from Barash 8e: ketorolac, CCBs, metoclopramide

• Drugs that are safe to use in porphyria (Miller 8e Ch 39): propofol, nitrous oxide, succinylcholine, meperidine, fentanyl, morphine, neostigmine, atropine, droperidol, promethazine, and chlorpromazine
• Sources: Miller 8e Ch 22 & Ch 39, Barash 8e Ch 24

Vasopressin

• Peptide hormone → made in the anterior hypothalamus → secreted mainly from the posterior pituitary
• Released in response to:

• Primarily: high osmolality (hypernatremia) → detected by hypothalamus → linear relationship
• Significant hypotension → detected by baroreceptors (cardiac atria, carotid sinus, aortic arch)
• Decreased intravascular volume → via renin-angiotensin pathway (AT2 stimulates vasopressin release)

• Factors that decrease/inhibit vasopressin release: ethanol, ANP (in response to volume overload), and cortisol
• Vasopressin has two actions: systemic vasoconstriction and reabsorption of water in the kidneys

• V1 receptor → systemic vasoconstriction → increases SVR

• Most intense in the skeletal muscle and skin vascular beds
• Not a pulmonary vasoconstrictor → no change in PVR → decreases PVR/SVR ratio

• V2 receptor → increased aquaporins → increased reabsorption of water in the renal tubule

• Two forms

• Arginine vasopressin (ADH) → peptide hormone → produced in the hypothalamus

• Dosage: wide range from 0.01 to 0.6 IU/minute
• Adverse effects: necrotic skin lesions

• Desmopressin (DDAVP) → more potent and longer-lasting V2 activity (minimal V1 activity)

• Causes release of Factor 8 and vWF from endothelium → procoagulant
• First line therapy for vWD Type 1 & 2
• Minimal V1 activity → minimal vasoconstriction

• Sources: Miller 8e Ch 95, Kaplan’s Cardiac Anesthesia 7e Ch 35 & 36

Electrolyte Abnormalities: ECG Changes

• Single most important electrolyte affecting cell membranes: potassium
• Potassium → affects T-waves, causes prolonged PR with both hyper- and hypokalemia

• Hyperkalemia → Tall T-waves, ↔ PR and QRS, ↓ P and R heights, ST-changes, heart block, asystole

• Can cause QT shortening (like hypercalcemia) - can happen with MTP

• Hypokalemia → Depressed T-waves and ST, ↑ U wave height, ↔ PR, arrhythmias (a-fib, PVC’s)

• Magnesium → prolonged PR

• Hypermagnesemia ⇒ ↔ PR and ↔ QRS (similar to hyperkalemia)
• Hypomagnesemia ⇒ ↔ PR and ↔ QT, a-fib

• Calcium → QT interval

• Hypercalcemia → shortened QT and shortened ST

• Treatment: first, IV fluid rehydration → then, loop diuretics, bisphosphonates → 2nd line: calcitonin

• Hypocalcemia → prolonged QT - can happen with MTP

• Hypokalemia/hypomagnesemia and hypercalcemia worsen digitalis toxicity
• Sources: Morgan & Mikhail 5e Ch 49, Barash 7e Ch 14

Mixed Venous Oxygen Saturation (SvO2)

• Measured in the proximal main pulmonary artery (mixture of both cardiac and systemic venous blood)

• Usually ScvO2 (central venous) is 5% higher (no coronary venous blood)
• Surviving sepsis: maintain SvO2 > 65% and ScvO2 > 70%

• Calculated as: SvO2 = SaO2 - [VO2 ÷ (CO x Hgb x 1.39)]
• Normal SvO2 is 65-75% ⇒ tissue oxygen extraction is 25-35%
• Normal PvO2 is 35-45 mmHg
• Increases in SvO2 ⇒ more oxygen delivery relative to extraction

• ↑ SaO2 → supplemental oxygen
• ↓ VO2 (decreased extraction)

• Cyanide toxicity → decreased consumption of O2 (↓ VO2)

• Treatment: hydroxocobalamin, amyl nitrite, sodium nitrite or sodium thiosulfate

• Hypothermia, sedation, analgesia, respiratory support
• COHb or MetHb without CO-oximetry

• SvO2 is falsely elevated because CoHb and MetHb are included in SaO2 measurement

• ↑ CO → sepsis (not septic shock), thyroid storm, AV fistula, cirrhosis, inotropes, IVF
• ↑ Hgb → blood transfusions

• Decrease in SvO2 (increased oxygen extraction relative to delivery)

• ↑ VO2 → exercise, shivering, MI
• Decreased oxygen delivery:

• COHb, MetHb → higher affinity for O2 → decreased delivery of oxygen → decreased SvO2

• Note: this is only true when saturation is measured via multi-wavelength CO-oximetry that is capable of detecting CoHb and MetHb

• ↓ SaO2 → pneumothorax, PE, atelectasis
• ↓ CO → tamponade, heart failure, shock (e.g. septic shock), hypovolemia, MI
• ↓ Hgb → blood loss, acute anemia

Note: COHb will cause ↓S⊽O2 only if CO-oximetry is used to get a true Hgb value

• Source: Miller 8e Ch 51

Pseudocholinesterase (PChE)

• Pseudocholinesterase (PChE) is also called butyrylcholinesterase (BChE), choline esterase II, or acetylcholine acylhydrolase → Synthesized mainly in the liver → found mainly in plasma and liver
• Hydrolyzes succinylcholine, mivacurium, procaine, chloroprocaine, tetracaine, and cocaine

• 90% of IV succinylcholine is rapidly hydrolyzed in plasma and liver by PChE → only 10% reaches NMJ
• Little/no PChE is present at the NMJ → neuromuscular blockade by succinylcholine is terminated by its diffusion away from NMJ into the circulation → PChE influences the onset and duration of action of SCh by controlling the rate of hydrolysis before it reaches (onset) and after it leaves (duration) the NMJ
• Drugs that may interfere with succinylcholine metabolism: neostigmine, pyridostigmine, echothiophate, cyclophosphamide, chlorpromazine, and organophosphate insecticides

• Decreased levels of PChE seen in: liver disease, infants, pregnancy, OCP use, malnutrition, organophosphate poisoning, cancer, burns, plasmapheresis
• Increased levels of PChE seen in: obesity, men (till age 45)

• Dibucaine number (DN) is a qualitative test (not quantitative) for abnormal PChE

• Normal: dibucaine inhibits 80% of normal PChE → dibucaine number (DN) 80 → SCh duration 5 mins
• Heterozygous atypical (1/500): DN 60 → SCh duration 15 minutes
• Homozygous atypical (1/3000): DN 20 → SCh duration >1 hour

• Do not confuse PChE with other (different) esterases which do not interact with succinylcholine

• Esmolol: metabolized by RBC cytosolic esterases
• Remifentanil: metabolized RBC and tissue non-specific esterases

• Donepezil (CNS AChE inhibitor used in Alzheimer’s) may prolong duration of succinylcholine Ref

• Only a weak inhibitor of PChE
• May cause resistance to non-depolarizing NMBA

• Sources: Barash 8e Ch 24, Miller 8e Ch 34, Henry's Clinical Diagnosis and Management 23e Ch 20, Complications in Anesthesia 3e Ch 98, 391-394, Meyler's Side Effects of Drugs 7e 615-641

Substance Use Disorder (SUD) Among Anesthesiology Residents

• Incidence of SUD among residents: 0.86%

• 34% successfully re-entered residency programs
• Death was the initial relapse symptom in 16% of opioid abusers allowed to reenter residency → recommended to redirect them to another specialty

• Highest rates have occurred since 2003
• Most common substances used (in order)

• Intravenous opioids (#1 was fentanyl)
• Alcohol
• Marijuana or cocaine
• Anesthetics/hypnotics (#1 was benzodiazepines followed by propofol, ketamine and inhaled agents)
• Oral opioids

• Mortality

• 7% died of SUD-related problems during the training period.
• 11% eventually died of a SUD-related cause
• Death was the initial relapse symptom in 16% of opioid abusers allowed to reenter residency

• Relapse: 43% of the survivors experienced at least one relapse within 30 years after the initial incident

• Risk factors: family history of substance abuse, major opioid abuse, coexisting psychiatric disorder

• Source: Warner DO, et al. JAMA 310.21 (2013): 2289-2296 (Data from 1975-2009), Menk EJ, et al. JAMA. 1990 Jun 13;263(22):3060-2., Barash 7e Ch 3, Miller 8e Ch 110

Drugs that act at the NMDA receptor

• NMDA receptor: glutamate-activated ion channel

• Conducts sodium (in), calcium (in), and potassium (out) ions

• Ketamine: potent, selective NMDA inhibitor

• Binds phencyclidine site on receptor

• Magnesium: NMDA antagonist activity

• Blocks NMDA ion channel at resting membrane potential → depolarization → removes Mg

• Nitrous oxide: main mechanism of anesthetic activity (plus ɑ-adrenergic, dopamine - minimal GABA)

Varying Sensitivity of Different Muscle Groups to NMBA

• Dosage

• Nondepolarizing agents (adductor pollicis muscle [APM] usually used as reference ← ulnar nerve)

• Diaphragm and laryngeal muscles are more resistant than peripheral muscles (APM) → need 1.5-2x higher dose to block diaphragm vs. adductor pollicis
• Muscles of the upper airway are more sensitive than peripheral muscles (APM)

• Since diaphragm is more resistant, breathing may recover before ability to maintain a patent airway or protect airway → this is why TOF > 0.9 is important

• Succinylcholine: only muscle relaxant that causes greater neuromuscular block at the vocal cords than at the adductor pollicis

• Onset: despite resistance, ONSET is faster at the diaphragm and laryngeal adductors (vs. APM)
• Recovery: greater resistance to neuromuscular blockade of respiratory muscles → faster recovery of the respiratory muscles vs. APM
• Other muscles

• Orbicularis oculi (moves eyelid) → recovery time course similar to APM
• Corrugator supercilii (moves eyebrow) → time course similar to laryngeal adductors
• Flexor hallucis brevis (contraction of big toe) → time course similar to APM
• Ulnar nerve stimulation → flexion of the fifth finger + APM contraction → Recovery of the fifth finger contraction occurs more rapidly than at the APM (fifth finger overestimates recovery at other muscles)

• Sources: Miller 8e Ch 34, Barash 8e Ch 21 p547-548

ACGME Core Competencies

• Six Core Competencies (from ACGME)

• Patient Care: compassionate, appropriate, and effective care
• Medical Knowledge: stay up to date with evolving medical knowledge
• Practice-Based Learning and Improvement

• Identify limits in one’s knowledge and expertise → set learning goals → perform learning activities
• Systematically analyze practice using quality improvement methods and implement changes
• Incorporate formative evaluation feedback into daily practice
• Apply evidence-based medicine
• Use information technology to optimize learning
• Participate in the education of patients, families, learners, and other healthcare professionals

• Interpersonal and Communication Skills: teamwork, consultant role, proper record keeping
• Professionalism: patient privacy and autonomy, accountability
• Systems-Based Practice

• Awareness and responsiveness to the larger context and system of health care
• Use other resources in the system to provide optimal health care
• Coordinate patient care within the healthcare system relevant to their clinical specialty
• Incorporate cost awareness and risk-benefit analysis into practice
• Advocate for quality patient care and optimal patient care systems
• Work in interdisciplinary teams to enhance patient safety and improve patient care quality
• Participate in identifying system errors and implementing potential systems solutions

• Examples in Anesthesia (Miller 8e Ch 9) → SBP and PBL are tricky to differentiate and usually tested

• Systems-Based Practice

• Coordinate patient care with other health care professionals and trainees from surgical teams and perioperative nursing teams
• Participate in the performance of the procedural “time out” before every procedure undertaken
• Keep dirty and clean equipment and medications separate.
• Patient with nerve injury—refer to QI/patient safety committee

• Practice-Based Learning and Improvement

• Patient with central line infection—compare prevention strategy with medical literature
• Discuss positive and negative outcomes of anesthetic care choices by following selected patients (chosen by discussion with one-on-one attending supervisor) postoperatively until discharge

• Sources: Miller 8e Ch 9, ACGME Common Program Requirements

Cricoid Pressure

• Cricoid pressure (also known as Sellick maneuver) may prevent spillage of gastric contents into the pharynx
• Technique: downward pressure with the thumb and index finger on the cricoid cartilage → displace cartilaginous cricothyroid ring posteriorly → compress underlying upper esophagus against the cervical vertebrae

• How much pressure? 10N while awake, 30N after induction of anesthesia

• Controversies about applying cricoid pressure:

• Lack of validation in models other than cadavers
• Reports of aspiration despite its use
• Can cause relaxation of the lower esophageal sphincter, which can favor regurgitation
• May make it harder to mask ventilate, worsen laryngoscopic view, or cause esophageal rupture
• MRIs show esophagus is laterally displaced in most patients → inadequate esophageal compression

• However, other MRI studies have shown that the hypopharynx is compressed (Rice et al.)

• Sources: Basics of Anesthesia 7e Ch 16, Barash 8e Ch 28, Rice et al. Anesth Analg. 2009;109:1546–52

Dynamic Markers of Volume Status

• Pulse Pressure Variation (PPV) and Systolic Pressure Variation (SPV) from arterial pressure analysis

• Physiology (see figure below)

• Left heart during inspiration

• Positive pressure ventilation → ↑ lung volume → compresses lung tissue → squeezes blood into left heart → ↑ LV preload → ↑ SV and CO
• ↑ intrathoracic pressure → ↓ LV afterload → ↑ SV and CO

• Right heart during inspiration

• ↑ intrathoracic pressure → ↓ venous return → ↓ RV preload → ↓ RV output
• ↑ lung volume → ↑ PVR slightly → ↑ RV afterload → ↓ RV output
• ↓ RV output → ↓ left sided filling → ↓ LV SV → ↓ Systemic Arterial Blood Pressure

• This cyclic variation in arterial pressure is the systolic pressure variation (SPV)

• SPV, PPV and SVV should not exceed 13-17% → if higher, patient has “residual preload reserve”

• Preload reserve: physiologic state in which intravascular volume expansion shifts the patient upward on the Frank-Starling curve → ↑ SV and CO → also known as “fluid responsive”

• Limitations:

• Most experiments done with TV >8 mL/kg and PEEP > 5 in patient with normal intraabdominal pressure and a closed chest
• Effect of position such as steep Trendelenburg or lateral position are unclear
• Pulmonary HTN and ↓ RVEF do not respond reliably to changes in intrathoracic pressure
• High respiratory rates + significant bradycardia → disrupt respiratory cycle-induced changes
• Aging: decreased arterial compliance + increased baseline pulse pressure → exaggerated PPV response → use higher PPV thresholds

• Photoplethysmography

• Pulse oximeter can be used as a photoplethysmograph → detects changes in blood volume
• Variations in pulse oximetry plethysmographic waveform (ΔPOP) → predicts fluid responsiveness
• More reliable in mechanically ventilated patients
• Limitations: sympathetic variations in regional circulation (i.e skin/extremities), temperature, light, dysrhythmias, children, mechanically ventilated unparalyzed patient, and open abdomen

• CVP variation is not as validated compared to PPV, SPV, and photoplethysmography

• Source: Miller 8e Ch 45 & 51, Image from Hofer & Cannesson (2011) 

MRI Safety

• Contraindicated devices

• Cardiac: Pacemakers or implantable cardioverter-defibrillators (ICDs)
• ENT: Cochlear implants
• Chronic Pain: Pumps or Nerve stimulators
• Other metal objects: aneurysm clips, metal fragments, or bullets
• Items with internal wires (e.g. pulmonary artery catheter, epidural catheters)

• Dangers

• Burns can be caused by non-fiberoptic pulse oximeter (due to capacitive coupling), ECG electrodes, coiled wires, metallic components of monitors
• Hearing loss: personnel in magnet room can have hearing loss from high-decibel acoustic noise

• Emergencies (information based on published MRI protocols from UCLA, Mayo Clinic, and University of Iowa)

• Cardiac arrest: Start BLS → patient should immediately be removed from the scanner room (Zone 4) and moved to a Zone 3 area for further resuscitation → crash cart and external defibrillator can be used here
• In general, patient should be moved out of the MRI magnet and Zone 4 scanning room for emergencies
• When to quench a magnet?

• Only when a person/object is pinned to the magnet and a person is at an immediate risk of harm

• Sources: Miller 8e Ch 90 and 109, Ontario Health Technology Assessment Series. 2003;3(7):1-16.

Bronchopulmonary Dysplasia (BPD)

• Chronic lung disease with oxygen dependence/requirement → most prominent in the first year of life

• Infants with mild BPD may eventually become asymptomatic, but airway hyperreactivity persists
• Incidence correlates with gestational age

• Mechanism: abnormal signaling by VEGF
• Treatment:

• Hypoxia and pulmonary hypertension + cor pulmonale → oxygen to keep PaO2 > 55 and SpO2 > 94%
• Reactive airway bronchoconstriction → bronchodilating agents
• Interstitial fluid retention and pulmonary edema → diuretics

• Anesthetic considerations

• Subglottic stenosis may be present → smaller size ETT may be needed
• Previous prolonged intubations → Tracheomalacia and bronchomalacia
• Airway hyperreactivity → deep plane of anesthesia prior to airway instrumentation

• Source: Stoelting’s 7e Ch 30, Smith's Anesthesia for Infants and Children 9e Ch 23

Laryngomalacia and Bronchomalacia

• Laryngomalacia → excessive flaccidity of the laryngeal structures (especially epiglottis and arytenoids)

• Most common cause of chronic stridor in children (70%)

• Congenital vocal cord paralysis is seen in approximately 10% of infants with congenital stridor
• Bronchomalacia → cartilage of the major airways is weakened → seen in infants with prolonged NICU course

• Risk factors: prolonged mechanical ventilation, poor nutrition, infections, growth impairment
• Clinical: bearing down → airway collapse
• Usually occurs with some BPD

• Source: Stoelting’s 7e Ch 30

Laryngeal Musculature

• All muscles supplied by RLN except cricothyroid muscle (supplied by external branch of SLN)
• Image Source: Marv Ruona (Art & Science Graphics) [Image]

NMJ AChR Upregulation

• Normal (mature junctional) nAChR → ACh binds both α-subunits → depolarization
• AChR is composed of five subunits → three types:

• Mature junctional receptor: 2 x α1-subunits + β1, δ7, ε → mostly intra-junctional
• Immature junctional receptor: 2 x α1-subunits + β7, δ7, γ (instead of ε) → extra-junctional
• 5 x α7 AChR subunits (skeletal muscle) → seen in sepsis, burns, immobilization

• These have lower affinity of ND-NMBAs → resistance → need higher doses
• More subunits that can bind ACh → more NMBA needed to block 5 α-receptors

• These aberrant receptors are responsible for the exaggerated hyperkalemic response to succinylcholine
• Upregulation seen in

• Nerve Injuries: Stroke, Spinal cord injury
• Burns (starts @ 24 hours → up to 1-2 years after burn injury)
• Prolonged immobility (risk greatest after 16 days)
• Prolonged exposure to neuromuscular blockers (e.g. paralysis in ICU)
• Myopathies: Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD)
• Denervation Disorders: Multiple sclerosis, Guillain-Barré syndrome, ALS

• Downregulation seen in:

• Myasthenia gravis
• Anticholinesterase poisoning (e.g. organophosphate)

• Sources: ABA Content Outline I.A.4.e.5, Miller 8e Ch 18, Miller 8e Ch 34

Pediatric Perioperative Fluid Management

• Neonates have reduced GFR → prone to volume overload
• Neonates have more sodium losses → poor response to aldosterone and ADH
• Large TBW relative to adults → clinical symptoms won’t show up till moderate dehydration (10% loss of TBW)
• Higher BSA to body weight ratio → increased evaporative losses
• Relatively fixed SV (noncompliant myocardium, reduced intracellular Ca2+ stores, reduced contractility)

• CO is almost entirely HR dependent (CO = SV x HR) → antimuscarinic agents for hypotension

• PNS dominant + immature baroreceptors → reduced response to hypotension
• Fluid administration concepts (may be outdated → replaced by goal-directed fluid therapy)

• Maintenance fluid requirements (4-2-1 rule)
• Existing deficits and NPO time → replace 33% of pre-op deficits over 1st hour
• Third space losses → based on invasiveness of procedures

• Superficial: 2-4 mL/kg/hr
• Moderate: 5-7 mL/kg/hr
• Major: 10-12 mL/kg/hr

• Blood loss → replace first 10-20% with crystalloids or colloids → after 20%, give blood products

• Source: Smith’s Anesthesia for Infants and Children 9e Ch 5

Neuraxial Anesthesia: Gastrointestinal Effects

• Blockade of T6-L1 → decreased splanchnic sympathetic innervation → contracted gut and hyperperistalsis

• Hyperperistalsis → nausea and vomiting → treat with atropine
• Contracted gut → excellent surgical conditions

• Gastric mucosa: epidural analgesia can increase intramucosal pH (vs. systemic opioids)
• Local anesthetics have anti-inflammatory properties → less GI irritation 
• Hepatic blood flow

• Spinal: reduction in hepatic blood flow (from hypotension)
• Lumbar epidural: decreased hepatic perfusion (despite colloid preloading)
• Thoracic epidural: hepatic perfusion can increase mildly (<10%) after major abdominal surgery

• Source: Miller 8e Ch 56

Herbal Medications: Perioperative Concerns

• Echinacea → activates cell-mediated immunity

• Decreases effectiveness of immunosuppressants
• Potential immunosuppression with long-term use
• Possible liver dysfunction
• Allergic reactions (especially in those with asthma, atopy, eczema)

• Ephedra → sympathomimetic agent → increased HR and BP

• Risk of HTN → MI and stroke
• Long term use → hemodynamic instability intraoperatively → use direct pressors (vs. ephedrine)
• Life-threatening interactions with MAOI → hyperpyrexia, hypertension, and coma
• Discontinue for 24 hours

• Garlic → inhibits platelet aggregation, increases fibrinolysis, possible antihypertensive

• May increase risk of bleeding especially combined with other inhibitors of platelet aggregation
• Inhibition of platelet aggregation is possibly irreversible → discontinue for 7 days

• Ginger → antiemetic, inhibits platelet aggregation

• May increase risk of bleeding → discontinue for 36 hours

• Ginseng → lowers glucose, inhibits platelet aggregation (irreversibly), increases PT/PTT

• Can cause hypoglycemia
• May increase risk of bleeding → more bleeding → discontinue for 7 days
• May decrease anticoagulant effect of warfarin → more clotting if on warfarin

• Green tea → inhibits platelet aggregation, inhibits TXA2 formation ⇒ risks similar to ginseng

• May increase risk of bleeding → more bleeding → discontinue for 7 days
• May decrease anticoagulant effect of warfarin → more clotting if on warfarin

• Kava → sedative and anxiolytic → discontinue 24h before

• May increase sedative effects of anesthetics

• Saw Palmetto → Inhibits 5α-reductase and COX

• May increase risk of bleeding

• St. John’s Wort → Inhibits neurotransmitter reuptake → used for depression

• Induction of P450 enzymes → affects cyclosporine, warfarin, steroids, and protease inhibitors

• May affect benzodiazepines, calcium channel blockers, and many other drugs

• Inhibits reuptake of serotonin, norepinephrine, and dopamine → may prolong effects of anesthesia
• Induces CYP2C9 → can decrease the effectiveness of warfarin
• Induces CYP3A4 → can decrease effectiveness of fentanyl, alfentanil, sufentanil, midazolam
• Discontinue 5 days before

• Valerian → sedation

• May increase sedative effect of anesthetics
• Benzodiazepine-like acute withdrawal
• May increase anesthetic requirements with long-term use

• Herbal Medications Grouped by effect

• Increased bleeding risk: garlic, ginger, ginkgo, ginseng, green tea, vitamin E, Saw palmetto
• Increased sedation: kava, valerian, St. John’s Wort
• Immune-modulation: echinacea
• Hepatic dysfunction: echinacea
• HTN, stroke, MI, hemodynamic instability: ephedra
• Decrease effectiveness of warfarin: St. John’s Wort, garlic, green tea
• Hypoglycemia: ginseng

• Source: Miller Ch 8e Table 40-1

Cardiac Reflexes

• Bainbridge (tachycardia)

• Afferent: atrial stretch receptors → vagal afferents
• Efferent: decreased parasympathetic → tachycardia 

• Bezold-Jarisch Reflex

• Afferent: noxious stimuli detected in left ventricular wall
• Efferent: triad of hypotension, bradycardia, and coronary artery dilation

• Valsalva Maneuver

• Increased intrathoracic pressure → increased CVP → decreased venous return → decreased CO and BP → baroreceptors sense low BP → sympathetic stimulation → increased HR and contractility

• Cushing Reflex (high ICP, bradycardia, and respiratory changes)

• Increased ICP → cerebral ischemia detected at the medullary vasomotor center → sympathetic activation → increase in HR, BP, myocardial contractility (to improve cerebral perfusion) → high vascular tone → reflex bradycardia mediated by baroreceptors

• Source: Miller 8e Ch 20

Epoprostenol

• Inhaled PGI2 used to treat pulmonary hypertension
• Complications

• Adverse reactions: diarrhea, jaw pain, headaches, and skin flushing (from vasodilation)
• 6 minute half-life → can cause systemic hypotension
• Dissolved in viscous and basic diluent → can cause tracheitis, interstitial pneumonia, ventilator valve malfunction → replace ventilator filter every 2 hours to avoid valve malfunction

• Source: Miller 8e Ch 104, Meyer’s Side Effects of Drugs 16e Ch Epoprostenol

Contrast-Induced Nephropathy (CIN)

• Risk factors: mainly CKD and diabetes; others include dehydration, old age, diuretic use, CHF, HTN
• Prevention:

• Most effective: aggressive hydration with normal saline
• Alkalinization of the urine with sodium bicarbonate may help
• N-acetylcysteine (Mucomyst) is controversial

• Source: Miller 8e Ch 96, Campbell-Walsh Urology 11e Ch 2

Opioids: Pruritus

• More common with neuraxial opioids (intrathecal > epidural)
• Mechanism:

• Neuraxial opioids → Medullary dorsal horn MOP activation → pruritus
• Systemic opioids → histamine release → pruritus
• KOP activation prevents pruritus → nalbuphine 2.5-4 mg and pentazocine 15 mg can treat it
• Serotonin is also an activator in itch pathway → ondansetron can treat it

• Opioids that cause histamine release: morphine, codeine, and meperidine
• Treatment

• Opioid antagonists, propofol, ondansetron, antihistamines, pentazocine, nalbuphine

• Antagonists are most effective → but they reduce analgesia

• Hydromorphone and intranasal butorphanol can reduce pruritus resistant to antihistamines

• Source: Wall & Melzack's Textbook of Pain 6e Ch 31, Miller 8e Ch 31

Preoperative Cardiac Evaluation Guideline (2014)

• 12-lead ECG

• Do not perform for low-risk surgical procedures (i.e. MACE < 1% → e.g. cataracts, plastics)
• For elevated-risk (MACE > 1%) procedures, reasonable in patients with (Class IIa):

• Known coronary heart disease, significant arrhythmia, significant structural heart disease
• Cerebrovascular disease or peripheral arterial disease
• Asymptomatic patients: may be reasonable to do it (class IIb)

• Assessment of LV function indications

• Dyspnea of unknown origin
• HF with worsening dyspnea or other change in clinical status

• Reassessment of LV function in clinically stable patients may be considered

• Routine preoperative evaluation of LV function is not recommended

• Exercise stress testing for MI and functional capacity

• Elevated risk + excellent functional capacity → no need for testing
• Elevated risk + moderate-good functional capacity → may not need testing
• Elevated risk + unknown functional capacity → exercise testing if it will change management
• Elevated risk + poor or unknown functional capacity → exercise testing with cardiac imaging to assess for myocardial ischemia
• Routine screening with noninvasive stress testing is not useful for low-risk noncardiac surgery

• Cardiopulmonary exercise testing: for elevated risk procedures
• Noninvasive pharmacological stress testing before noncardiac surgery

• Elevated risk + poor functional capacity → either DSE or MPI if it will change management

• Routine preoperative coronary angiography is not recommended
• Source: 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation

NIM EMG Endotracheal Tube

• Function: EMG monitoring of the laryngeal musculature
• Use the biggest possible tube that is safe → to ensure good electrode contact with vocal cords

• “one size larger than standard selection… to improve electrode contact with vocal cords”

• Correct tube positioning: electrodes should be in contact with the vocal cords

Note: These images are for the Medtronic NIM TriVantage ETT

• Warnings

• Avoid using lidocaine for lubricating the tube → false positive for vocal cord dysfunction
• Avoid using paralyzing agents → can’t monitor laryngeal muscles with EMG if paralyzed
• Avoid deep anesthesia → can cause false negatives
• Avoid rotating, flexing, or extending the patient’s head and neck once tube is positioned

• Contraindications

• Postoperative ventilation
• Not approved for infants/neonates
• Flammable: avoid in procedures with lasers or flammable gases

• Source: Medtronic NIM EMG Endotracheal Tube - Manual (2015)

Preoperative Potassium Levels

• Major concern with abnormal potassium levels: cardiac function (electrical disturbance, poor contractility)
• Hyperkalemia ECG changes

• Earliest manifestations: narrowing and peaking of the T wave
• Progressively widening QRS complex that merges with the T wave into a sine wave
• K > 6.7 mEq/L → degree of hyperkalemia correlates with duration of the QRS complex
• K > 7 mEq/L→ decreased P-wave amplitude, increased PR interval

• Hypokalemia ECG changes

• Widening of the QRS complex, ST-segment abnormalities (ST-depression)
• Progressive decrease in T-wave amplitude
• Progressive increase in the U-wave amplitude

• Decision to proceed with surgery in potassium abnormalities (Source: Clinical Anesthesia Procedures of the MGH 9e)

• ECG changes seen with either hypokalemia or hyperkalemia → generally warrants treatment
• No ECG changes

• Chronic mild hypokalemia (K+ > 2.5; e.g. diuretics): proceed with noncardiac surgery
• Chronic mild hyperkalemia (K+ < 6; e.g. ESRD): proceed with noncardiac surgery

• Acute changes in potassium are more dangerous than chronic changes
• Cardiac Surgery: K+ < 3.5 is a predictor for dangerous perioperative arrhythmias (Miller 8e)
• Potassium replacement has its own risks (IV > oral) and should be used judiciously

• Source: Miller 8e Ch 39, Clinical Anesthesia Procedures of the Massachusetts General Hospital 9e Ch 1

Stress Hyperglycemia

• Overall: increased hepatic and renal glucose production + insulin resistance
• Stress → increased hormones: epinephrine, norepinephrine, glucagon, cortisol, growth hormone
• Primary mechanism: epinephrine → glucagon release → hepatic gluconeogenesis         

• Need gluconeogenesis because glycogen stores are rapidly depleted

• Insulin resistance

• TNF-α → decreases insulin receptor sensitivity → insulin resistance
• Increased GH → but decreased hepatic GH receptors → decreased IGF-1
• Proinflammatory cytokines → decreased IGF-1

• Source: Pediatric Critical Care (Fuhrman) 5e Ch 85, Evidence-Based Practice of Anesthesiology 3e Ch 25

Postoperative Jaundice

• Mild liver enzyme elevation (< 2x upper limit of normal) can occur after surgery (abdominal procedures)

• Asymptomatic, mild elevations of hepatic enzymes → back to normal in 2 days

• Normally: unconjugated bilirubin → enters liver cell → gets conjugated → conjugated bilirubin exits liver cell
• Unconjugated (indirect) bilirubinemia

• Excessive bilirubin production (hemolysis)

• Resorption of hematomas
• PRBC transfusion → 10% of transfused RBCs hemolyze within 24 hours → high bilirubin load → liver takes time to clear bilirubin load → elevated unconjugated bilirubin
• Hemoglobinopathies (e.g., sickle cell), erythrocyte metabolism defects (e.g., G6PD), transfusion reactions, prosthetic heart valves

• Immature liver enzymes: physiologic jaundice of newborn, jaundice of prematurity
• Inherited defects

• Gilbert syndrome (impaired uptake of indirect bilirubin into liver cells)
• Crigler–Najjar syndrome (impaired conjugation of indirect bilirubin in liver cells)

• Drug effects: halothane, antibiotics, etc.

• Conjugated (direct) bilirubinemia

• Hepatocellular disease (hepatitis, cirrhosis, drugs)
• Intrahepatic cholestasis (drugs, pregnancy)
• Congenital conjugated hyperbilirubinemia

• Dubin-Johnson syndrome (impaired exit of direct bilirubin + black liver)
• Rotor syndrome (impaired exit of direct bilirubin; no black liver)

• Obstructive jaundice

• Extrahepatic (calculus, stricture, neoplasms)
• Intrahepatic (sclerosing cholangitis, neoplasm, primary biliary cirrhosis)

• Source: Barash 7e Ch 45, Miller 8e Ch 73 

Post-Cardiac Transplant Patient

• Recipient SA node not retained in modern bicaval techniques → two P waves on post transplant ECG is of historic interest only

• Donor atrium is responsible for heart rate generation
• Recipient (remnant) atrium generates heart rate but impulses do not cross suture line

• Transplanted heart is isolated from the recipient’s nervous system

• No parasympathetics → resting heart rate is faster than normal at 90-110 bpm

• Direct activation of myocardial receptors (e.g., adrenergic receptors) is retained
• Intrinsic myocardial reflexes and mechanisms retained (e.g., Frank-Starling, Anrep effect [↑afterload → ↑inotropy], Bowditch effect [↑HR → ↑inotropy], vasoconstrictive effect on coronary arteries of hypocarbia)
• Transplanted heart is critically preload-dependent because it cannot ramp up HR
• Drugs effects

• Direct-acting drugs (epinephrine, dobutamine, norepinephrine, isoproterenol) → inotropy
• Pacing, isoproterenol → chronotropy
• Indirect-acting drugs (e.g., ephedrine, dopamine) → release of epi and norepi from adrenals
• Digoxin

• Inhibition of Na/K-ATPase → buildup of intramyocardial Ca2+ → inotropy
• But no decrease in chronotropy (parasympathetic effect on the AV node)

• Response to anticholinergics: diminished (meperidine, pancuronium, anticholinergics) → no ↑ HR

• Denervated heart → accelerated atherosclerosis → but no angina (dysrhythmias are the first sign)
• Source: Miller 8e Ch 67

PONV Guidelines (2014)

• General incidence of nausea is 50% and vomiting is 30%
• Risk factors for PONV

• Patient specific

• Female gender (strongest patient-specific predictor)
• History of PONV
• Non-smoking status
• History of motion sickness
• Age < 50

• Anesthesia/Surgery related

• Volatile anesthetics (strongest anesthesia-related predictor)
• Duration of anesthesia
• Postoperative opioid use
• Use of nitrous oxide (risk can be canceled by propofol induction and PONV prophylaxis)
• Type of surgery (cholecystectomy, laparoscopic, gynecological)

• Apfel score for PONV (female, nonsmoker, history of PONV/motion sickness, post op opioids)

• 0-1 → low risk → 10-20% incidence of PONV
• 2 → medium risk → 40% incidence of PONV
• 3+ → high risk → >60% incidence of PONV

• Risk factors for PDNV (incidence: almost 40%)

• Female gender (same as PONV)
• Age < 50 years
• History of PONV (same as PONV)
• Opioid use in the PACU
• Nausea in the PACU

• Risk factors for PONV in children

• Duration of surgery > 30 minutes
• Age > 3 years
• History of POV in patient, parent or sibling
• Type of surgery: strabismus

• Strategies to reduce baseline risk of PONV

• Avoidance of general anesthesia → use regional instead
• Use propofol (antiemetic properties) for induction and maintenance
• Avoidance of nitrous oxide (little impact when baseline risk is low)
• Avoidance of volatile anesthetics (mostly cause early PONV 0-2 hrs after surgery)
• Use of TIVA with propofol appears to decrease both nausea and vomiting 1,2
• Minimization of opioids (especially postoperatively)
• Adequate IV fluid hydration (no difference in crystalloid vs. colloid)
• No longer recommended due to weak/conflicting evidence

• Minimizing neostigmine dose
• Supplemental oxygen

• Other therapies that work:

• P6 acupuncture point stimulation → similar efficacy to ondansetron
• Median nerve stimulation (tetanus) intraoperatively
• Low-dose naloxone infusion (0.25 mcg/kg/h)
• Subhypnotic propofol infusion in pediatric patients

• Things that do not work: Music therapy, isopropyl alcohol inhalation, intraoperative gastric decompression, esomeprazole, ginger root, nicotine patch (for nonsmokers), cannabinoids
• Main Source: Gan TJ, et al. Anesthesia & Analgesia 118.1 (2014): 85-113.

Malignant Hyperthermia (MH)

• Normal: skeletal muscle depolarization → brief opening of RYR1 (ryanodine-sensitive calcium channel receptors) on sarcoplasmic reticulum → influx of Ca++ into cell → brief muscle contraction
• Increased susceptibility to MH with four muscle disorders: masseter spasm (trismus), central core disease, multiminicore disease, and King-Denborough syndrome
• Malignant hyperthermia: RYR1 or CaV1.1 defect + presence of volatile agents or succinylcholine → prolonged channel opening → sustained muscle contraction

• Volatile agents: onset can be later with desflurane or isoflurane compared to sevoflurane
• Increase in EtCO2, tachycardia, tachypnea, hyperthermia, and metabolic acidosis
• Results in a generalized hypermetabolic state →

• Sinus tachycardia
• Increased CO2 → acidosis
• Lactic acid → acidosis
• Heat production (as much as 1° C in 5 minutes) → hyperthermia
• Muscle cell breakdown →

• Hyperkalemia → arrhythmias
• Rhabdomyolysis → renal failure, liver failure, organ failure

• Treatment

• Dantrolene (2.5 mg/kg): mechanism unknown; interacts with Ca2+ channels

• Avoid calcium-channel blockers (verapamil, diltiazem) → interacts with dantrolene to worsen hyperkalemia → arrhythmias and cardiovascular collapse
• Initial Dose: 2.5 mg/kg q5-10 minutes up to 10 mg/kg (up to 4 doses total)
• Maintenance for 24-48 hours: 1 mg/kg bolus q4h or 0.25 mg/kg/hr infusion

• Arrhythmias → amiodarone, lidocaine, procainamide
• Renal failure (from rhabdomyolysis) → use diuretics like furosemide or mannitol
• Acidosis → sodium bicarbonate

• Diagnosis

• In vitro contracture test (IVCT; Europe) and Caffeine-Halothane Contracture Test (CHCT; America)
• Muscle biopsy (vastus group from quadriceps preferred site → then rectus abdominis → others)
• Expose biopsied muscle to increasing caffeine and halothane → increased tension = positive
• If positive response to either caffeine or halothane → MH positive; if both negative → MH negative
• Genetic testing is not as sensitive because new genes/alleles are being identified all the time

• Source: Miller 8e Ch 43

Cardiac Output Measurement: Thermodilution

• Thermodilution method: injectate goes from CVP-port to thermistor within pulmonary artery

• CO calculated based on the degree and speed of temperature change (smaller = higher CO)

• High cardiac output → less time for mixing of injectate and blood → less temperature change
• If you use less injectate → less temperature change detected → Calculated CO higher than it really is
• Right-sided valve (tricuspid/pulmonic) regurgitation → less reliable CO measurements
• Respiratory cycle can affect CO calculation (especially during positive-pressure ventilation) because you are measuring right-ventricular cardiac output (which is affected more by respiratory cycle)

Glasgow Coma Scale (GCS)

• Eye → 4 (spontaneous, to speech, pain, none)
• Verbal → 5 (oriented, answers questions but confused, inappropriate but with recognizable words, incomprehensible sounds, none)
• Motor → 6 (obeys, localizes, withdraws, decorticate [flexed], decerebrate [extended], none)
• Modifiers: C = eyes closed; I/T = intubated
• Moderate brain injury = GCS 9-12 (severe < 9; minor > 12)
• SBP < 90 mmHg and PaO2 < 60 mmHg are very poor prognostic indicators in severe TBI
• E.g. opens eyes to pain only, no verbal responses, withdraws to painful stimuli. GCS? 7 ⇒ E2V1M4
• E.g. intermittent words but unable to answer questions, eyes open to pain, withdraws extremities to pain → GCS9

Sympathetic Cardiac Innervation

• Receptors involved: ɑ1, β1 and β2

• ɑ1: increased contraction (inotropy)
• β1: everything is increased → HR (chronotropy), contraction (inotropy), conduction (dromotropy), and relaxation (lusitropy)
• β2: increased HR (chronotropy) > contraction (inotropy)

• Originates from T1-T4 → stellate ganglion →

• Right stellate ganglion → HR (chronotropy)
• Left stellate ganglion → MAP and contractility (inotropy) → can be blocked for LQTS

Double-Lumen Tubes

• Left-sided double lumen tube = left-sided endobronchial tube with tracheal tube

• Cuffs: tracheal cuff, endobronchial cuff
• Lumen: tracheal lumen, endobronchial lumen
• With normal placement as shown in figure:

• Tracheal cuff inflated + endobronchial cuff inflated:

• Air through bronchial lumen → left-sided lung sounds only
• Air through tracheal lumen → right-sided lung sounds only

• Tracheal cuff inflated only

• Air through either lumen → bilateral breath sounds

• Disadvantage of right-sided DLT: can occlude RUL takeoff due to proximity

Frank-Starling Curves

1. Pure inotrope or inotrope with vasoconstriction (e.g. norepinephrine, epinephrine)
2. Inotrope + vasodilator (e.g. milrinone)
3. Vasodilator (e.g. nicardipine, hydralazine)
4. Inotrope + vasodilator + diuretic
5. Diuretic

EEG Frequencies

• Alpha waves: prominent during relaxation with eyes closed
• Beta waves (high frequency, low amplitude): during periods of arousal
• Delta waves (low frequency, high amplitude): deep coma, encephalopathy and deep anesthesia

• E.g. opioid infusion during CEA will cause increased amplitude and decreased frequence

• Theta waves: children and may be seen in encephalopathy
• Isoelectric EEG: maximal decrease in CMRO2 
• Burst suppression

• Desired EEG pattern with propofol, etomidate and thiopental
• Represents maximal CMRO2 reduction while indicating that regular EEG activity will return predictably following cessation of infusion

• Indications for EEG monitoring

• Surgeries: CEA, cardiac bypass, cerebrovascular surgery (clipping/bypass procedures)
• ICU: barbiturate coma for TBI, or subclinical seizures suspected

Infections and Blood Transfusions

• Most common (Source: Barash 7e)

• #1 overall: bacterial (1 in 3,000) → mostly with platelets (stored at room temperature)
• #1 viral: CMV (1 in 4,000 with leukoreduction) > Hepatitis B > HTLV > Hepatitis C > HIV

• CMV → hides in leukocytes → leukoreduction reduces transmission
• For patients at high risk (immunocompromised) → blood from CMV-seronegative donors

Cervical Spine Stabilization

• Goal: maintain head, neck and shoulders in neutral position (Images)
• Two person technique

• First operator ⇒ stabilize head/neck: fingertips grasp mastoid processes + palms cradle occiput
• Second operator ⇒ stabilize shoulders: hold them against bed
• Avoid sniffing position or distraction of the spine

• Proper manual in-line stabilization (MILS) during intubation (right image): operator applies downward pressure on the mastoid processes to keep the spine stable during laryngoscopy using his/her (operator’s) forearm and elbow on patient’s chest to stabilize the position

• “... assistant's hands are placed on each side of the patient's face with the fingertips resting on the mastoid process and application of downward pressure against a firm table surface to hold the head immobile in a neutral position” Stoelting’s Ch 11

AHA/ACC Surgery Classification

• Temporal necessity of operations

• Emergency: life or limb is threatened if not in the OR, typically within <6 hours
• Urgent: time for a limited clinical evaluation, usually when life or limb is threatened if not in OR, typically between 6 and 24 hours
• Time-sensitive procedure: delay of >1 to 6 weeks to allow for an evaluation and significant changes in management will negatively affect outcome

• In pregnancy, OK to delay these so procedure can be performed in second trimester → lower chances of preterm labor or miscarriage

• Elective: procedure could be delayed for up to 1 year 

• Risk-based (MACE = major adverse cardiac event)

• Low-risk procedure: risk of MACE < 1% (e.g. cataract, plastic surgery)
• Elevated-risk: risk of MACE of ≥ 1%

Arterial Blood Pressure Monitoring Waveforms

As you go more peripheral → increased reflected waves from branch points in the arterial tree → higher peaks in both the systolic and diastolic pressure curves

• Systolic pressure increases → more pronounced systolic wave
• Diastolic pressure increases (less) → more pronounced diastolic wave
• Pulse pressure widens

Dicrotic notch: aorta is highly elastic and recoils once the aortic valve closes → further propelling forward flow → seen as the dicrotic notch (red arrows)

• More sharp/pronounced centrally
• More delayed (dark blue box) and slurred distally

Brachial artery cannulation complications:

• Median nerve injury (runs closely with brachial artery in antecubital fossa)
• Lack of collateral circulation → distal ischemia (rare)
• Infection rate 1:1,000

Axillary artery cannulation

• Pros: Excellent collateral circulation if injured (less risk of ischemia), larger vessel
• Cons: harder to repair due to location, possible brachial plexus injury if hematoma forms

Intraoperative Radiation Exposure

• Total exposure is affected by three factors

1. Total radiation exposure time → cumulative (recommended < 5000 mrem/yr)
2. Total radiation exposure intensity → chest x-ray = 5-10 mrem; CT = 5000 mrem
3. Distance from source → Intensity ∝ 1/distance2 ⇒ double distance → 1/4th radiation intensity

• Eyes are the most sensitive organs to effects of radiation → increased risk of cataracts
• Most of the radiation comes from scattering, not directly from the beam

Spinal Anesthesia Spread

• Factors affecting spinal (intrathecal) anesthesia spread

• Baricity = density of a substance relative to the density of CSF
• Patient positioning
• Drug dosage but not volume
• Age → spread is greater with older age
• CSF volume (accounts for 80% of variability) → more CSF volume = less spread → but no clinical/anthropometric predictors available (i.e. age, gender, height, BMI, etc. can’t predict this)
• Intraabdominal pressure (higher pressure [e.g. pregnancy] → higher block level)
• Minor factors: speed of injection and needle direction

• Total spinal

• In adults: sympathectomy → hypotension, bradycardia → → apnea → hypoxia
• In children: apnea is the first sign (relatively immature SNS → so no significant sympathectomy)

Uterine Defects and Rupture

• Uterine defect: uterine scar separation, mild uterine scar dehiscence → no fetal distress, non-emergency
• Uterine rupture → full-thickness uterine wall compromised → hemorrhage, fetal distress → emergency

• Maternal mortality increases when rupture occurs in setting of no prior uterine scar
• Risk-factors:

• Previous scar (upper segment scar 5-10x >> lower segment scar)
• Uterine manipulation (e.g. external cephalic version) and trauma, weak uterus (prolonged labor, induction), overdistended uterus (polyhydramnios)

• Previous vaginal birth is a protective factor
• Most common signs: fetal bradycardia (75%), change in uterine contractions, pain (10%)

NMBA in Pediatrics

• Adult fluid compartments: TBW = 60% of body weight (BW); ICF = 40% BW; ECF = 20% BW
• Pediatric fluid compartments (TBW = total body water)

• Infants: TBW = 75% BW; ECF = 40% BW (till age 2 → then it becomes like adults)
• Preterm infants: TBW = 85% BW

• Succinylcholine: larger doses needed in infants (2-2.5 mg/kg vs. 1-1.5 mg/kg in adults)

• Ok to use for emergency situations
• Avoid in elective situations: risk of hyperkalemia with undiagnosed muscular dystrophies
• Can cause bradycardia and sinus node arrest

• Especially in children → PNS is more developed (than SNS) → more ACh receptors → more stimulation of cardiac muscarinic receptors (mACh-R)
• Attenuated by atropine 
• In adults: bradycardia after 2nd dose from succinylmonocholine (metabolite of 1st dose)

• Succinylmonocholine may sensitize SA node to SCh stimulation of mACh-R

• Can also cause tachycardia with very large doses

• Rocuronium and vecuronium: Kids have decreased hepatic metabolism → stick around longer
• Pancuronium: Kids also have immature renal enzymes → slower excretions → longer duration of action
• Complete maturation of NMJ occurs at 2 months
• Infant’s diaphragm and peripheral muscles get paralyzed at the same time

Uterine Relaxation

• For treatment of uterine inversion → surgical emergency

• Also for retained placenta

• First line: nitroglycerin (IV or sublingual) → increases cGMP → NO → fast-onset, short-acting

• Can cause hypotension → get good IV access and start fluid administration
• Side effects: headache → treat with vasopressor (phenylephrine)
• Good option in hemodynamically stable patient without hemorrhage

• Second line: general anesthesia with volatile anesthetics (except N2O, which doesn’t relax the uterus)

• Better option in unstable patient with hemorrhage

• Other options: inhaled amyl nitrite, magnesium, β-adrenergic agonists (IV terbutaline, ritodrine, or salbutamol)
• β-adrenergic agonist side-effects:

• Tachycardia (like albuterol) with or without cardiac dysrhythmias or MI
• Hypokalemia (like albuterol, due to direct β2-agonism)
• Hypotension
• Pulmonary edema
• Liver (glycogenolysis) + pancreas (glucagon): Maternal hyperglycemia → neonatal hypoglycemia

Labor Stages

• Stage I: onset of contractions → cervix completely dilated

• Latent phase: contractions without much cervical dilation

• Most common cause of prolongation is “unripe” cervix, another cause is false labor
• Prolongation not associated with fetal distress or cephalopelvic disproportion → no increase in the rate of cesarean delivery
• For analgesia, need to cover T10-L1 (uterus and cervix) → analgesia methods include epidural, spinal, CSE, paracervical block, remifentanil infusion

• Active phase: higher rate of cervical dilation (regular 2-3 minute intervals)

• Primary dysfunctional labor: cervix not dilating fast enough
• Secondary arrest of dilation: no cervical dilation for two hours 
• Prolongation → fetal distress or cephalopelvic disproportion → increased cesarean rate

• Stage II: cervix fully dilated → baby is delivered

• Also innervated by S2-S4: vaginal wall → analgesia methods include: spinal, CSE, epidural and saddle (pudendal nerve) block (paracervical block won’t be enough)

• Stage III: baby is delivered → placenta is delivered

Preeclampsia

• Definition (from the 2013 update by ACOG)

• Hypertension >140/90 after 20-weeks of gestation
• Proteinuria: 24-hour urine protein > 300 mg or urine P/C ratio > 0.3
• Severe features

• BP >160/110
• Platelets <100,000
• Impaired liver function: AST/ALT > 2x normal or RUQ pain
• Renal insufficiency: Cr > 1.1 or 2x baseline
• Pulmonary edema (crackles, CXR)
• Neuro: cerebral (headaches) or visual symptoms (scotomas, black spots)

• In the absence of proteinuria, hypertension + severe feature = preeclampsia

• Pathophysiology

• Vascular hyperreactivity → high SVR + uterine vasoconstriction → decreased placental flow
• Increased vasoconstrictive factors: thromboxane A2 (TxA2), endothelin-1 (ET-1)
• Decreased vasodilatory factors: PGI2, NO
• Endothelial cell activation

• → decreased NO → hypertension
• → platelet activation → thrombocytopenia

• Decreased renal blood flow → increased Cr
• Capillary leakage → pulmonary edema

Neuraxial Anesthesia for Labor and Delivery

• Levels for first stage of labor: T10-L1 (uterus, cervix)
• Levels for second stage of labor T10-S4 (uterus, cervix and perineum)

• Saddle (pudendal nerve) block → only provides anesthesia for S2-S4 (second stage)

• Level for cesarean delivery: T4 (stomach and intestines innervated by greater splanchnic nerve T5-T10)
• Shivering

• Occurs with labor normally, but more frequent with neuraxial anesthesia
• Cause: peripheral vasoconstriction (sympathetic block below level) → drop in core temperature

• Intrathecal: 30x higher risk of pruritus
• Combined Spinal-Epidural (CSE) for labor analgesia

• Benefits: rapid onset of analgesia, decreased incidence of failed epidural analgesia
• Drawbacks: unproven epidural catheter, higher incidence pruritus
• Relatively contraindicated in patients for whom a functional epidural catheter is critical for safety (anticipated difficult airway, non-reassuring fetal heart tones, high likelihood of cesarean delivery)

Sub-Ambient Pressure Alarm

• Identified breathing system pressure less than -10 cmH2O during spontaneous or controlled ventilation
• Common causes:

• Spontaneous respiration with an obstruction in the circuit
• Scavenging system problems (e.g. excess scavenger flow or expiratory valve stuck on “open”)
• Application of a suction device into the circuit (e.g. NG tube in the trachea)

APGAR score

Chloroprocaine

• Ester local anesthetic → rapidly metabolized by plasma cholinesterases → very little placental transfer

• Unlike amides which are hepatically cleared

• Short-acting (30-60 minutes), fast-onset (6-10 minutes) [plasma half-life = 15 seconds]
• Placental transfer of local anesthetics depends primarily on four factors:

• Lipid solubility → more soluble = more transfer across placenta
• pKa of the local anesthetic → non-ionized = more transfer

• Chloroprocaine has a pKa of 9 (relatively high) → however, onset is fast because of high concentrations (3%)

• Maternal and fetal pH → low pH → more ionization of local anesthetic → “ion trapping”

• Chloroprocaine has minimal “ion trapping”

• Degree of protein binding → more binding = less transfer

Acute Epiglottitis - Airway Management

• Epiglottitis → variable extrathoracic obstruction → airway collapses on inspiration → use CPAP with mask ventilation to maintain open airway
• Induction: inhalational induction with sevoflurane/oxygen in sitting position

• Avoid desflurane → can trigger laryngospasm
• Avoid NMBA → can worsen pharyngeal muscle tone → worsen obstruction

• Intubation: use smaller endotracheal tube

Flow-Volume Loops

Epinephrine in Obstetric Neuraxial Anesthesia

• Benefits

• ɑ1-agonism → vasoconstriction of epidural vessels → prolongs duration of analgesia
• ɑ2-agonism → decreases MLAC (analogous to MAC; kinda like clonidine and Precedex)
• No actual effect on uterine tone, contractions, or duration of labor (theoretically possible)
• Faster-onset of local anesthetics
• Enhanced efficacy of opioids

• Drawbacks: Increased intensity of motor block, drug errors, theoretical uterine relaxation (β2-agonism)

Neuraxial α2-agonists

• Drugs: Clonidine, dexmedetomidine, and epinephrine
• Mechanism: act on prejunctional and postjunctional α2 receptors in the dorsal horn of the spinal cord

• Presynaptic receptors → reduces neurotransmitter release
• Postjunctional receptor → hyperpolarization and reduction of pulse transmission

• Clonidine

• Equivalent analgesia to morphine but much longer duration of action
• Synergistic with morphine: clonidine (30 μg) prolongs duration and reduces morphine consumption
• Side effect: hypotension (no bradycardia)
• Also causes some sedation with spinal clonidine (peaking within 1 to 2 hours, lasting up to 8 hours)

• Dexmedetomidine: even 3 μg can prolong blockade by without hemodynamic compromise Ref
• Source: Miller Ch 56, Kanazi GE, et al. Acta Anaesthesiologica Scandinavica 50.2 (2006): 222-227

Cryoprecipitate

• Contains FIVE main components (vWF, 8, 13, fibrinogen, fibronectin)

• 100 IU of Factor VIII:C
• von Willebrand factor (vWF)
• Factor XIII
• 250 mg of Fibrinogen → clot stabilizer and platelet activator
• Fibronectin

• Administration: as rapidly as possible (at least 200 mL/hr) through a filter
• Indications (Source: Barash, Clinical Anesthesia, 7th Edition, Table 16-7)

• Hemophilia: used for emergency back up when factor concentrates are unavailable
• von Willebrand's disease: dDAVP first line, then factor concentrates, lastly cryoprecipitate
• Hypofibrinogenemia: usually < 80-100 mg/dL
• Bleeding from excessive anticoagulation: but FFP is a better choice
• Massive bleed – RBCs and volume expanders are preferred therapies.
• DIC