ANSWER: B

Rationale:

Phenobarbital is one of the most potent CYP450 inducers in clinical use. It induces CYP2C9, the primary cytochrome P450 isoform responsible for S-warfarin metabolism, as well as CYP1A2, CYP2B6, CYP2C19, CYP3A4, and UDP-glucuronosyltransferases (UGTs). CYP2C9 induction increases the rate of warfarin catabolism, reducing steady-state warfarin plasma concentrations and thereby decreasing anticoagulant effect — reflected here by the falling INR. This interaction develops insidiously over days to weeks as enzyme induction requires de novo protein synthesis, explaining why the INR did not fall immediately but only became apparent two weeks into therapy. INR monitoring and warfarin dose adjustment are essential when phenobarbital is initiated or discontinued; the reverse interaction — rising INR and hemorrhagic risk — occurs when phenobarbital is stopped without reducing the warfarin dose.

• Option A: Option A: Protein displacement interactions do not meaningfully reduce INR in the sustained manner shown here; displacement would transiently increase free warfarin and raise the INR, not lower it, and is not a mechanism of phenobarbital interaction with warfarin.
• Option B: Option B: This is correct. Phenobarbital induces CYP2C9, the primary enzyme metabolizing the more pharmacologically active S-enantiomer of warfarin, increasing its clearance and reducing anticoagulant effect.
• Option C: Option C: Vitamin K epoxide reductase is the direct target of warfarin itself, not a site of phenobarbital action; phenobarbital has no direct effect on this enzyme.
• Option D: Option D: While phenobarbital does induce P-glycoprotein, the dominant mechanism of this clinically significant interaction is hepatic CYP2C9 induction rather than gut efflux; P-gp effects on warfarin bioavailability are not the primary driver of this well-characterized pharmacokinetic interaction.
• Option E: Option E: Phenobarbital is an inducer, not an inhibitor, of CYP2C9; competitive inhibition would increase warfarin levels and raise the INR, which is the opposite of what is observed.

ANSWER: D

Rationale:

The clinical picture — high-dose prolonged propofol infusion, metabolic acidosis with elevated anion gap, rhabdomyolysis with myoglobinuria (pink urine), hypertriglyceridemia, and hemodynamic deterioration — is diagnostic of propofol infusion syndrome (PRIS). The core mechanism of PRIS involves propofol-mediated impairment of mitochondrial electron transport chain function (specifically at complex I and complex II) combined with inhibition of free fatty acid oxidation. This creates a state of cellular energy failure: tissues cannot generate ATP via oxidative phosphorylation, forcing a switch to anaerobic glycolysis and producing lactic acidosis. The concurrent inability to oxidize fatty acids results in lipid accumulation (hypertriglyceridemia) and fatty infiltration of cardiac and skeletal muscle. Cardiac muscle involvement produces the characteristic PRIS cardiomyopathy — new right bundle branch block or ST-segment changes on ECG are an early warning — while skeletal muscle involvement causes rhabdomyolysis. Risk factors include infusion rates above 4–5 mg/kg/hr (approximately 67–83 mcg/kg/min), infusion duration beyond 48 hours, high carbohydrate intake, and critical illness with catecholamine or steroid co-administration. PRIS carries a mortality of approximately 30% and the only definitive treatment is immediate discontinuation of propofol.

• Option A: Option A: Propofol is a positive allosteric modulator of GABA-A receptors at all clinically relevant concentrations; it does not competitively inhibit them at any dose, and paradoxical excitation is not a mechanism of PRIS.
• Option B: Option B: Glutathione depletion and hepatocyte lipid peroxidation are not the established mechanism of PRIS; while transaminase elevation can occur, direct hepatocyte necrosis by this pathway does not explain the cardiac and skeletal muscle involvement or the anion-gap acidosis.
• Option C: Option C: The lipid vehicle can cause hypertriglyceridemia, but renal tubular obstruction is not a recognized mechanism of PRIS; the elevated anion gap and multi-organ energy failure are attributable to mitochondrial dysfunction, not obstructive nephropathy.
• Option D: Option D: This is correct. PRIS is caused by propofol-mediated inhibition of mitochondrial electron transport at complexes I and II and impaired free fatty acid oxidation, producing cellular energy failure, lactic acidosis, rhabdomyolysis, hypertriglyceridemia, and cardiomyopathy.
• Option E: Option E: Adrenocortical 11-beta-hydroxylase inhibition is the mechanism of etomidate-induced adrenal suppression, not propofol; propofol does not inhibit this enzyme.

ANSWER: A

Rationale:

Etomidate produces adrenocortical suppression by selectively inhibiting 11-beta-hydroxylase (CYP11B1), the enzyme responsible for converting 11-deoxycortisol to cortisol in the zona fasciculata of the adrenal cortex. The mechanism is direct binding of etomidate to the heme iron center of this cytochrome P450 enzyme, blocking its catalytic activity. After a single induction dose, this suppression typically lasts 12–24 hours; with continuous infusion, suppression is sustained and substantially more severe — which is why continuous etomidate infusion for ICU sedation has been abandoned. In this case, the patient's refractory hypotension and low cortisol 12 hours after a single induction dose is consistent with etomidate-induced relative adrenal insufficiency superimposed on the already-stressed adrenal axis of septic shock. The clinical significance of single-dose etomidate-induced adrenal suppression in sepsis remains debated — randomized trials including KETASED have not demonstrated definitive mortality harm — but the pharmacological mechanism itself is well established and uncontested.

• Option A: Option A: This is correct. Etomidate selectively inhibits 11-beta-hydroxylase (CYP11B1) by binding to its heme iron center, blocking the final step in cortisol synthesis and producing transient adrenocortical insufficiency lasting 12–24 hours after a single dose.
• Option B: Option B: Etomidate does not act on hypothalamic CRH receptors; its adrenal suppression is a direct enzymatic effect at the adrenal cortex, not a central hypothalamic-pituitary mechanism.
• Option C: Option C: Propylene glycol vehicle toxicity produces renal tubular injury and osmol gap elevation with prolonged infusion; it does not cause adrenal cortical necrosis, and the vehicle is not the mechanism of etomidate's well-characterized adrenal suppression.
• Option D: Option D: Cholesterol side-chain cleavage enzyme (CYP11A1) catalyzes the first committed step in steroidogenesis; etomidate does not inhibit this enzyme — its selective target is 11-beta-hydroxylase further downstream in the cortisol biosynthetic pathway.
• Option E: Option E: Etomidate does not interact with ACTH receptors; its mechanism is intracellular enzymatic inhibition within the adrenal cortex, not receptor-level antagonism of the ACTH signaling pathway.

ANSWER: C

Rationale:

Ketamine's cardiovascular stimulatory effects — tachycardia, hypertension, and increased cardiac output — are mediated indirectly through the sympathetic nervous system rather than through direct cardiac receptor activation. Ketamine inhibits neuronal catecholamine reuptake (analogous to cocaine's mechanism) and simultaneously stimulates central sympathetic outflow from the brainstem, resulting in elevated circulating epinephrine and norepinephrine levels. This indirect sympathomimetic mechanism is the reason ketamine is the preferred induction agent in hemorrhagic shock and other low-perfusion states: it counteracts the cardiovascular depression of hypovolemia by harnessing the patient's own catecholamine reserves. An important clinical caveat is that in catecholamine-depleted states — such as prolonged septic shock or end-stage cardiogenic shock — ketamine's sympathomimetic effect may be blunted or absent, and direct myocardial depression (an intrinsic property of ketamine) may predominate, causing cardiovascular collapse. This is distinct from its mechanism in the current patient, who has acute hemorrhagic shock with intact sympathetic reserves.

• Option A: Option A: Ketamine does not directly activate beta-1 adrenergic receptors; its cardiovascular stimulation is indirect, mediated through elevated circulating catecholamines secondary to reuptake inhibition and central sympathetic activation.
• Option B: Option B: Muscarinic M2 receptor blockade is the mechanism of anticholinergic agents such as atropine; ketamine does not have clinically significant antimuscarinic activity and this is not the basis of its cardiovascular effects.
• Option C: Option C: This is correct. Ketamine stimulates cardiovascular function indirectly by inhibiting neuronal catecholamine reuptake and activating central sympathetic outflow, elevating circulating norepinephrine and epinephrine — the mechanism that makes it the preferred induction agent in hemorrhagic shock.
• Option D: Option D: Ketamine is an NMDA receptor antagonist, not an agonist; it blocks rather than activates NMDA receptors, and direct vasomotor center NMDA agonism is not its cardiovascular mechanism.
• Option E: Option E: Phosphodiesterase inhibition is the mechanism of agents such as milrinone and theophylline; ketamine does not inhibit phosphodiesterase and this pathway does not account for its cardiovascular stimulatory profile.

ANSWER: E

Rationale:

Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that produces its sedative effect primarily through agonism at presynaptic alpha-2 receptors on locus coeruleus neurons, inhibiting norepinephrine release and reducing central arousal signaling. The resulting sedation state is unique among ICU sedatives: patients are sedated but remain arousable — capable of responding to voice and following commands — without requiring dose reduction or infusion interruption. This property of cooperative sedation makes dexmedetomidine uniquely suited to light sedation protocols, neurological monitoring, and early mobilization. Critically, dexmedetomidine does not produce clinically significant respiratory depression at therapeutic doses, unlike benzodiazepines, propofol, and opioids — all of which suppress hypercapnic and hypoxic ventilatory drive. In this COPD patient with marginal respiratory reserve, preservation of ventilatory drive while maintaining assessable sedation is a compelling pharmacological advantage. The PADIS (Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption) guidelines (Devlin et al., Crit Care Med 2018) recommend dexmedetomidine over benzodiazepine infusions for ICU sedation, in part because of these properties.

• Option A: Option A: Dexmedetomidine does not act on GABA-A receptors; its mechanism is alpha-2 adrenergic agonism at the locus coeruleus, and its sedation profile resembles natural sleep rather than GABA-mediated sedation.
• Option B: Option B: While dexmedetomidine has some analgesic properties mediated through spinal alpha-2 receptors, NMDA receptor blockade is the mechanism of ketamine, not dexmedetomidine; and the primary reason for selecting it here is its unique arousability profile, not spinal analgesia.
• Option C: Option C: Dexmedetomidine does not act at mu-opioid receptors; its receptor selectivity is for alpha-2 adrenergic receptors, and the respiratory-sparing property derives from the absence of opioid-receptor-mediated ventilatory depression, not a ceiling effect.
• Option D: Option D: This option correctly identifies the locus coeruleus presynaptic alpha-2 mechanism but incorrectly describes the resulting sleep stage as slow-wave sleep; dexmedetomidine produces a sedation state more closely resembling stage 2 non-REM sleep, and the option omits the defining clinical property of arousability and lack of respiratory depression that directly answers the question.
• Option E: Option E: This is correct. Dexmedetomidine produces cooperative, arousable sedation through alpha-2 adrenergic agonism at the locus coeruleus without clinically significant respiratory depression — the two properties that directly support its selection in this mechanically ventilated COPD patient on a light sedation protocol.

ANSWER: B

Rationale:

Barbiturate overdose has no specific antidote — unlike benzodiazepine overdose, which is reversible with flumazenil, there is no receptor-level reversal agent for barbiturate toxicity. Management is entirely supportive: mechanical ventilation for respiratory failure, vasopressors and IV fluids for hemodynamic support, temperature management for hypothermia, and close monitoring. However, phenobarbital has two specific elimination-enhancing interventions that distinguish it from other barbiturates. First, multi-dose activated charcoal exploits phenobarbital's enterohepatic recirculation — phenobarbital is secreted into the gut lumen and reabsorbed, and repeated charcoal dosing interrupts this cycle, increasing total body clearance. Second, urinary alkalinization with IV sodium bicarbonate increases renal elimination of phenobarbital by ion trapping: phenobarbital is a weak acid (pKa approximately 7.2), and alkalinizing the urine to pH 7.5–8.0 keeps it in its ionized form in the renal tubule, reducing passive reabsorption and increasing urinary excretion. These two interventions are specific to phenobarbital among the barbiturates and are not applicable to shorter-acting barbiturates such as thiopental or methohexital.

• Option A: Option A: Flumazenil is a competitive antagonist at the benzodiazepine binding site on GABA-A receptors and does not reverse barbiturate-mediated GABA-A potentiation; barbiturates bind to a distinct site on the GABA-A receptor complex and flumazenil has no activity there.
• Option B: Option B: This is correct. Phenobarbital overdose is managed supportively, with multi-dose activated charcoal to interrupt enterohepatic recirculation and urinary alkalinization with sodium bicarbonate to enhance renal elimination via ion trapping — interventions specific to phenobarbital among the barbiturates.
• Option C: Option C: Physostigmine reverses anticholinergic toxidrome; barbiturate overdose produces CNS and respiratory depression without anticholinergic features, and physostigmine has no role in barbiturate poisoning management.
• Option D: Option D: Phenobarbital has a relatively low volume of distribution (approximately 0.6–0.7 L/kg) and moderate protein binding, making it one of the more dialyzable barbiturates; however, hemodialysis is reserved for severe life-threatening cases refractory to supportive care and charcoal, and is not the primary or first-line strategy — it is an adjunct when the measures in option B are insufficient.
• Option E: Option E: IV lipid emulsion is used for local anesthetic systemic toxicity (particularly bupivacaine) due to the high lipophilicity of local anesthetics; while phenobarbital has some lipid solubility, IV lipid emulsion is not an established treatment for barbiturate overdose and is not recommended in current toxicology guidelines for this indication.

ANSWER: D

Rationale:

Remimazolam contains a unique ester linkage in its molecular structure that is cleaved by widely distributed non-specific tissue esterases — not by hepatic cytochrome P450 enzymes — to an inactive carboxylic acid metabolite. This esterase-mediated hydrolysis confers two clinically important pharmacokinetic advantages over midazolam. First, the metabolism is context-insensitive: recovery time after remimazolam infusion is approximately 5–10 minutes regardless of infusion duration, because esterase activity is not saturable in the way that hepatic oxidative metabolism becomes with prolonged midazolam infusion (where peripheral compartment accumulation substantially extends recovery). Second, because metabolism is CYP450-independent, remimazolam has no pharmacokinetic drug interactions through the CYP3A4 pathway — a direct advantage over midazolam in this patient taking multiple CYP3A4 inhibitors, which would significantly prolong midazolam's effect. In addition, esterase activity is generally preserved in hepatic impairment, making remimazolam substantially more predictable than midazolam in this patient's setting. Like all benzodiazepines, remimazolam is fully reversible with flumazenil — a meaningful safety advantage over propofol, for which no reversal exists.

• Option A: Option A: Remimazolam is not metabolized by CYP3A4; its esterase-mediated hydrolysis specifically avoids the CYP450 pathway, and its metabolite is inactive — accumulation of an active metabolite is the pharmacokinetic liability of midazolam, not remimazolam.
• Option B: Option B: Remimazolam is not eliminated by renal filtration of unchanged drug; it is metabolized by tissue esterases to an inactive metabolite, and its pharmacokinetics are not significantly affected by renal impairment.
• Option C: Option C: Remimazolam has a shorter, not longer, duration of action than midazolam; high protein binding creating a peripheral reservoir and sustained plasma levels describes the pharmacokinetic liability of long-acting benzodiazepines such as diazepam, not remimazolam.
• Option D: Option D: This is correct. Remimazolam undergoes ester hydrolysis by non-specific tissue esterases to an inactive metabolite, producing context-insensitive ultra-short offset of approximately 5–10 minutes that is independent of infusion duration, hepatic function, and CYP450 drug interactions.
• Option E: Option E: Remimazolam, like all benzodiazepines, binds reversibly to the benzodiazepine site on GABA-A receptors; irreversible receptor binding is not a property of any clinically used benzodiazepine, and remimazolam's duration of action is determined by its rapid esterase metabolism, not by receptor binding kinetics.

ANSWER: A

Rationale:

The American Society of Anesthesiologists (ASA) defines four levels along the sedation continuum, and the transition from moderate to deep sedation represents a clinically critical threshold. At the level of deep sedation, patients cannot be easily aroused but do respond purposefully to repeated or painful stimulation — distinguishing deep sedation from general anesthesia, in which patients are not arousable even to pain. Spontaneous ventilation may be inadequate at deep sedation levels, meaning the patient may require airway support, supplemental oxygen, or assisted ventilation, but cardiovascular function is usually maintained. This contrasts with moderate sedation, at which patients respond purposefully to verbal commands with or without light touch, spontaneous ventilation is adequate, and no airway intervention is required. The clinical implication of the continuum is that patients can move unintentionally from their target sedation level to a deeper level, and the provider must be prepared to manage the complications of that deeper level — particularly airway compromise and ventilatory inadequacy. This is the basis for the ASA requirement that providers administering moderate sedation be trained and equipped to manage deep sedation and airway emergencies.

• Option A: Option A: This is correct. Deep sedation is defined by purposeful response only to repeated or painful stimulation, possible inadequacy of spontaneous ventilation requiring airway intervention, and generally preserved cardiovascular function — the level that moderate-sedation providers must be trained to manage.
• Option B: Option B: This description matches minimal sedation (anxiolysis), not deep sedation; at minimal sedation, patients respond normally to verbal commands and airway protective reflexes and cardiovascular function are unaffected.
• Option C: Option C: This description matches general anesthesia, not deep sedation; complete unarousability and absent ventilation are features of general anesthesia, whereas deep sedation preserves purposeful response to painful stimulation and cardiovascular function.
• Option D: Option D: Purposeful response to verbal commands without tactile stimulation and fully adequate spontaneous ventilation describe moderate sedation, not deep sedation; the transition to deep sedation is marked by loss of reliable response to voice and the emergence of ventilatory inadequacy.
• Option E: Option E: Paradoxical excitation is an uncommon adverse reaction to benzodiazepines in certain populations (children, elderly, patients with anxiety disorders), not a defining feature of the deep sedation level in the ASA continuum; flumazenil reversal of paradoxical excitation is a separate clinical scenario unrelated to sedation depth classification.

ANSWER: C

Rationale:

The MENDS trial (Pandharipande et al., JAMA 2007) was a randomized controlled trial that enrolled 106 mechanically ventilated adults and compared dexmedetomidine infusion to lorazepam infusion for ICU sedation. The primary finding was that dexmedetomidine-treated patients spent more time within their target Richmond Agitation-Sedation Scale (RASS) sedation score — demonstrating superior sedation quality — and had significantly more days alive without delirium or coma (delirium/coma-free days, the primary outcome), and less cognitive impairment at hospital discharge. The MENDS trial was foundational in shifting ICU sedation practice away from benzodiazepine infusions and provided direct evidence supporting guideline recommendations against routine lorazepam or midazolam infusions for most mechanically ventilated ICU patients. The subsequent MENDS2 trial compared dexmedetomidine to propofol (not lorazepam) in a larger septic shock and respiratory failure cohort and found no significant overall difference in delirium/coma-free days, with a subgroup benefit for dexmedetomidine in hypoactive delirium — establishing that the findings described in option E belong to MENDS2, not the original MENDS trial.

• Option A: Option A: The MENDS trial compared dexmedetomidine to lorazepam, not propofol; the finding favored dexmedetomidine, not lorazepam or propofol, and the comparison described in this option corresponds to the later MENDS2 trial.
• Option B: Option B: The MENDS trial compared dexmedetomidine to lorazepam, not midazolam, and the result was not equivalence — dexmedetomidine was superior on delirium/coma-free days; the setting was not post-cardiac surgery but rather a mixed mechanically ventilated ICU population.
• Option C: Option C: This is correct. The MENDS trial demonstrated that dexmedetomidine produced better RASS target attainment, more delirium/coma-free days, and less cognitive impairment at discharge compared to lorazepam in mechanically ventilated ICU patients.
• Option D: Option D: The MENDS trial did not demonstrate a 30% mortality reduction; its primary outcome was delirium/coma-free days, and while cognitive outcomes were improved, a definitive mortality benefit was not the primary or established finding of the MENDS trial.
• Option E: Option E: The finding described — dexmedetomidine superiority in hypoactive delirium versus propofol — is the subgroup finding of the MENDS2 trial, not the original MENDS trial, which compared dexmedetomidine to lorazepam and did not perform this delirium-phenotype subgroup analysis.

ANSWER: E

Rationale:

The ultra-short clinical duration of thiopental after a single induction dose is one of the classic illustrations of the principle of redistribution as distinct from metabolism. Thiopental is highly lipophilic and after IV bolus rapidly crosses the blood-brain barrier to achieve peak brain concentrations within 30–60 seconds, producing unconsciousness. However, the CNS represents only a small fraction of total body mass, and over the subsequent 5–10 minutes, thiopental redistributes from the well-perfused brain to skeletal muscle (a larger compartment), and subsequently to adipose tissue (the largest peripheral compartment). As brain concentrations fall due to redistribution — not due to metabolism — consciousness is rapidly restored. The drug is not eliminated at this point; it has simply redistributed to peripheral tissues. Hepatic metabolism (primarily by CYP2C19 oxidation) then proceeds slowly over many hours as drug re-equilibrates from fat and muscle back into the central compartment for elimination, producing the long elimination half-life of 10–12 hours. The clinical consequence of this pharmacokinetics is that repeated doses or continuous infusion of thiopental saturates the peripheral compartment, eliminating the redistribution advantage and producing prolonged sedation — the practical reason thiopental is unsuitable for maintenance sedation or infusion, and why it has been largely replaced by propofol in modern anesthetic practice.

• Option A: Option A: Thiopental does not undergo rapid hepatic glucuronide conjugation as its primary metabolic pathway; it is oxidized by CYP2C19, a process that takes hours, not minutes — the brief clinical effect is entirely due to redistribution, not rapid metabolism.
• Option B: Option B: P-glycoprotein efflux at the blood-brain barrier is not the mechanism of thiopental's brief clinical effect; while P-gp transporters do influence CNS penetration of some drugs, thiopental's redistribution from brain to peripheral tissues is a passive pharmacokinetic process driven by concentration gradients and tissue perfusion.
• Option C: Option C: Thiopental is not significantly renally cleared as a parent drug; it is a weak acid with pKa approximately 7.6 and is substantially protein-bound, and renal filtration does not account for its brief clinical duration.
• Option D: Option D: Thiopental does not undergo spontaneous plasma hydrolysis to an inactive product; it is chemically stable in solution, and its brief clinical effect is due to redistribution rather than chemical degradation.
• Option E: Option E: This is correct. Thiopental's brief clinical duration after a single dose reflects rapid redistribution from the brain to muscle and then fat, not hepatic metabolism; the drug accumulates in peripheral compartments and is released slowly for hepatic elimination over 10–12 hours, explaining the discrepancy between clinical duration and elimination half-life.

ANSWER: B

Rationale:

Etomidate has two well-characterized adverse effects on induction that are distinct from other IV induction agents. First, myoclonus — involuntary muscle jerking — occurs in approximately 40–80% of patients during induction and is thought to reflect subcortical disinhibition rather than true seizure activity. It can be confused with seizures but lacks the EEG correlate of ictal activity. Pre-treatment with a small dose of midazolam (1–2 mg IV) or a low-dose opioid (such as fentanyl) substantially reduces its incidence and severity. Second, etomidate is the most emetogenic of the commonly used IV induction agents — the incidence of postoperative nausea and vomiting (PONV) is higher with etomidate than with propofol (which has intrinsic antiemetic properties) or ketamine. For procedures with high baseline PONV risk, prophylactic antiemetic administration (ondansetron, dexamethasone, or both) is routinely recommended when etomidate is used. These two adverse effects, together with adrenocortical suppression, constitute the three clinically most important adverse effects of etomidate to recognize and manage in practice.

• Option A: Option A: Etomidate is notable for its hemodynamic stability — it produces minimal changes in blood pressure, heart rate, and cardiac output, which is its primary advantage over propofol and ketamine in hemodynamically unstable patients; significant hypotension and bronchospasm are not characteristic etomidate adverse effects.
• Option B: Option B: This is correct. Etomidate causes myoclonus in 40–80% of patients on induction and is the most emetogenic IV induction agent; pre-treatment with midazolam or a small opioid dose reduces myoclonus, and prophylactic antiemetic therapy is recommended.
• Option C: Option C: Malignant hyperthermia is triggered by volatile halogenated anesthetics and succinylcholine, not by etomidate; etomidate does not trigger malignant hyperthermia and dantrolene pre-treatment is not indicated for etomidate administration.
• Option D: Option D: Etomidate produces minimal respiratory depression compared to propofol and barbiturates — preservation of spontaneous ventilation is one of its advantages for induction in patients with compromised airways; laryngospasm is not a characteristic adverse effect, and glycopyrrolate pre-treatment is not part of standard etomidate use.
• Option E: Option E: Etomidate does not cause clinically significant histamine release — it is actually preferred in patients with reactive airway disease or atopy because of its low histaminergic profile; myocardial depression with etomidate is minimal compared to propofol, not equivalent to it.