Etomidate

At-a-glance clinical use

Induction agent with relative cardiovascular stability; rapid onset and short duration after single bolus
- Commonly chosen when hypotension is undesirable (e.g. severe cardiac disease, haemodynamic instability)
- Not ideal for septic shock/critical illness due to adrenal suppression concerns
Typical induction dose: 0.2–0.3 mg/kg IV (reduce in elderly, shocked, co-administered opioids/benzodiazepines)
- Onset ~30–60 s; duration ~3–5 min after a single bolus (redistribution)
Key adverse effects: myoclonus, pain on injection, PONV, and dose-dependent adrenal suppression
- Myoclonus reduced by opioid/benzodiazepine pre-treatment and slower injection

When to consider / avoid

Consider: severe LV dysfunction, critical aortic stenosis, poor cardiac reserve, haemodynamic instability where maintaining SVR/CO is important
- Also useful when avoiding histamine release/bronchospasm (minimal histamine release)
Avoid/think twice: sepsis/septic shock, prolonged ICU sedation, known adrenal insufficiency, porphyria (avoid as a precaution in many exam answers)
- Single bolus can suppress cortisol synthesis for hours; clinical significance greatest in septic/critically ill patients

Practical administration points

Formulation: lipid emulsion (commonly) or propylene glycol (older) — lipid reduces injection pain and thrombophlebitis compared with propylene glycol
- Inject via a large vein; consider lidocaine/opioid to reduce pain and myoclonus
No analgesia; ensure adequate opioid/adjuncts if stimulating procedures follow
- Can cause PONV—consider prophylaxis in at-risk patients

Chemistry and formulation

Imidazole carboxylate derivative; weak base; supplied as racemic mixture
Poor water solubility → formulated in lipid emulsion (most current preparations) or propylene glycol (older)
Concentration commonly 2 mg/mL (check local preparation); typical adult induction 10–20 mg depending on weight/dose

Mechanism of action (CNS)

Positive allosteric modulator at GABAA receptor → increased inhibitory neurotransmission
- Enhances GABA-mediated chloride conductance; produces hypnosis and amnesia
No intrinsic analgesic effect

Pharmacokinetics (exam-friendly)

Rapid onset due to high lipid solubility and rapid brain uptake; short duration after bolus due to redistribution
High protein binding (notably albumin); reduced albumin may increase free fraction and effect
Metabolism: hepatic ester hydrolysis and extrahepatic metabolism (including plasma/tissue esterases) → inactive metabolites
Elimination: renal (major) and biliary (minor) excretion of metabolites
Context-sensitive half-time: short for single bolus; not used for prolonged infusion due to adrenal suppression risk

Pharmacodynamics: cardiovascular

Minimal reduction in SVR and myocardial contractility compared with propofol/thiopentone → relative haemodynamic stability
- Typically small changes in HR and BP; baroreflex relatively preserved
Does not provide sympathetic stimulation; hypotension can still occur in hypovolaemia/with opioids

Pharmacodynamics: respiratory and CNS

Respiratory depression/apnoea can occur, but generally less than propofol at equipotent doses; potentiated by opioids
Reduces cerebral metabolic rate (CMRO2), cerebral blood flow (CBF), and intracranial pressure (ICP) while maintaining cerebral perfusion pressure via stable MAP
- EEG: burst suppression at higher doses
Can provoke myoclonus (non-epileptic) and may complicate interpretation in seizure-prone patients

Endocrine: adrenal suppression (high-yield)

Inhibits adrenal mitochondrial 11β-hydroxylase (and to a lesser extent 17α-hydroxylase) → reduced cortisol and aldosterone synthesis
- Effect can occur after a single induction dose and may last ~6–24 hours (variable by patient and assay)
Clinical relevance: associated with adrenal insufficiency and worse outcomes in sepsis in some studies; avoid repeated doses/infusions in critically ill

Adverse effects and interactions

Myoclonus (common): reduced by opioids, benzodiazepines, magnesium, or small priming dose; slower injection helps
Pain on injection and thrombophlebitis: worse with propylene glycol formulations; reduced with lipid emulsion and lidocaine/large vein
PONV: relatively high incidence compared with propofol; consider antiemetic prophylaxis
Allergy/anaphylaxis: rare; consider lipid emulsion component issues similarly to other lipid-based drugs
Drug interactions: synergistic hypnosis with opioids/benzodiazepines; additive respiratory depression

Comparisons (common FRCA contrasts)

Versus propofol: more haemodynamically stable, less vasodilation; more myoclonus and PONV; propofol has antiemetic effect and no adrenal suppression
Versus thiopentone: similar rapid onset; etomidate more stable haemodynamics; thiopentone more hypotension and histamine release; thiopentone contraindicated in acute porphyria
Versus ketamine: ketamine supports BP/HR via sympathetic stimulation and provides analgesia; etomidate lacks analgesia and suppresses adrenal steroidogenesis

Describe etomidate: class, formulation, and typical dose for induction.

Structure your answer as: class → formulation → dosing and time course.

Imidazole-derived IV hypnotic agent; produces hypnosis/amnesia via GABAA modulation
Poor water solubility → supplied as lipid emulsion (current) or propylene glycol (older; more injection pain)
Induction dose 0.2–0.3 mg/kg IV (reduce in elderly/shock/with opioids); onset ~30–60 s; duration ~3–5 min after bolus

How does etomidate affect the cardiovascular system and why is it considered 'stable'?

Mention SVR, contractility, HR, and baroreflexes; then clinical implication.

Relatively minimal reduction in SVR and myocardial contractility compared with propofol/thiopentone
Heart rate often unchanged; baroreflex relatively preserved → less hypotension
Still can cause hypotension in hypovolaemia or with high opioid doses; not a vasopressor

Explain the mechanism and clinical significance of etomidate-induced adrenal suppression.

This is a common FRCA viva: enzyme, hormones affected, duration, and who it matters in.

Inhibits adrenal mitochondrial 11β-hydroxylase (± 17α-hydroxylase) → reduced cortisol (and aldosterone) synthesis
Can occur after a single induction dose; suppression may persist for hours (often quoted ~6–24 h, variable)
Clinical concern greatest in sepsis/critical illness: avoid infusions and repeated dosing; consider alternative induction agents when feasible

What are the CNS effects of etomidate? Include ICP and seizure-related points.

Cover CMRO2/CBF/ICP, EEG, and myoclonus.

Decreases CMRO2 and CBF → decreases ICP; stable MAP helps maintain CPP
EEG: dose-dependent slowing and burst suppression at higher doses
Myoclonus is common and usually non-epileptic; can be confused with seizure activity

List the main adverse effects of etomidate and how you would reduce them.

Give adverse effect → mitigation.

Myoclonus: reduce with opioid or benzodiazepine pre-treatment, small priming dose, and slower injection
Pain on injection/thrombophlebitis: use lipid formulation, large vein, lidocaine, avoid small hand veins
PONV: consider prophylactic antiemetics and avoid if high PONV risk and alternatives acceptable
Adrenal suppression: avoid infusion/repeated doses; avoid in sepsis/known adrenal insufficiency where possible

A previous FRCA-style question: 'Compare etomidate and propofol for induction.' Give a structured comparison.

Use headings: haemodynamics, respiration, CNS, adverse effects, endocrine, and recovery/PONV.

Haemodynamics: etomidate causes less vasodilation and myocardial depression → more stable BP; propofol commonly causes hypotension
Respiration: both can cause apnoea; propofol tends to cause more respiratory depression at equipotent doses
CNS/ICP: both reduce CMRO2/CBF/ICP; etomidate preserves MAP more, potentially supporting CPP
Adverse effects: etomidate more myoclonus and PONV; propofol antiemetic and causes less myoclonus
Endocrine: etomidate suppresses adrenal steroidogenesis; propofol does not

A previous FRCA-style question: 'Why might etomidate be a poor choice in septic shock?'

Link physiology of sepsis to cortisol dependence and etomidate’s enzyme inhibition.

Septic shock may involve relative adrenal insufficiency and dependence on adequate cortisol response for vascular tone and catecholamine sensitivity
Etomidate inhibits 11β-hydroxylase → blunts cortisol synthesis for hours after a single dose
Association in studies with increased risk of adrenal insufficiency and potentially worse outcomes; therefore many guidelines/units avoid it in sepsis when alternatives exist

A previous FRCA-style question: 'Discuss causes and management of myoclonus with etomidate.'

Define it, why it matters, and prevention/management.

Myoclonus: involuntary muscle jerks during induction; can interfere with monitoring, increase aspiration risk, and be mistaken for seizures
Mechanism: thought to be subcortical disinhibition during onset of hypnosis (not typically epileptiform)
Prevention: opioid (e.g. fentanyl), benzodiazepine (e.g. midazolam), small priming dose of etomidate, slower injection
If occurs: ensure airway protection, deepen anaesthesia, treat as needed; consider alternative agent next time

How does etomidate affect respiration compared with other induction agents?

State the general effect and key modifiers.

Can cause dose-dependent respiratory depression and apnoea; generally less than propofol at equipotent doses
Markedly potentiated by opioids and other sedatives

Outline the pharmacokinetics of etomidate relevant to induction and recovery.

Focus on onset, redistribution, metabolism, and excretion.

Rapid onset due to high lipid solubility and brain uptake; short clinical duration after bolus due to redistribution
Metabolised mainly by hepatic and extrahepatic ester hydrolysis to inactive metabolites
Metabolites excreted predominantly in urine; some biliary excretion