| Class | IV anaesthetic |
|---|---|
| Chemistry |
A dextrorotatory R-ethyl ester of an imidazole carboxylic acid (i.e. related to dexmedetomidine, as both include an imidazole ring, but with a sufficiently different structure to have a completely distinct pharmacophore)
|
| Routes of administration |
Intravenous only |
| Absorption |
Zero oral bioavailability
|
| Solubility |
pKa 4.2, pporly water soluble (requires 35% propylene glycol to act as a solvent in the injectable formulation)
|
| Distribution |
4.5 L/kg VOD; 75% protein-bound, predominantly to albumin. VOD varies wildly from textbook to textbook depending on what compartment they are measuring (values in excess of 70L/kg for the redistribution volume are often mentioned)
|
| Metabolism |
Rapid clearance by hydrolysis via plasma and hepatic estherases
|
| Elimination |
Terminal elimination half-life is roughly 2–5 hours, but the distribution half-life is approximately 2–3 minutes (i.e. rapid offset of effect is mainly because redistribution)
|
| Time course of action |
Onset of effect following an induction dose (~0.3mg/kg) is within 15-30 seconds, i.e. one arm-brain circulation time.
|
| Target receptor |
GABAA ligand-gated chloride channels, principally receptors containing β2 or β3 subunits. |
| Mechanism of action |
Etomidate is a positive allosteric modulator and co-agonist at GABAA receptors, where its mechanism (hyperpolarisation of the neuron by the resulting post-synaptic chloride current) is stereoselective and mediated mostly by β2/β3-containing receptors (Yang and Uchida, 1996; Belelli et al, 1997). The β3-subunit-containing receptors are thought to be the ones responsible for most of the sedation. A completely unrelated and largely unwelcome effect is the binding of the imidazole moiety to the adrenal CYP enzyme 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2). This inhibits cortisol and aldosterone synthesis. This inhibition occurs within the first 30 minutes, results in a measurable fall of steroid titres in the next 6-8 hrs, and lasts 24-48 hrs after the dose (a single induction dose is enough to do this). |
| Clinical effects |
Hypnosis, amnesia, sedation; reduces cerebral metabolic rate (20-30%) and intracranial pressure while generally preserving cerebral perfusion pressure. There is a dose-dependent suppression of the respiratory drive, but less than with propofol. Zero intrinsic anticonvulsant effects, so preserves EEG activity (and in fact can cause myoclonus). The necessary manipulation of the injectable medium makes it irritant and a cause of thrombophlebitis. Minimal haemodynamic effects, but not zero haemodynamic effects. Comparing it to ketamine, which is the other strongest contender for the title of the most "cardio-stable" induction agent, etomidate produced peri-intubation cardiovascular collapse less frequently than ketamine (17.0% versus 22.1% in the RSI trial by Casey et al, 2025) which means 17% of patients still became unstable. |
| Literature reference |
Casey, Jonathan D., et al. “Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults.” New England Journal of Medicine, vol. 394, no. 16, 2026, pp. 1608–1620. doi:10.1056/NEJMoa2511420. Forman, Stuart A. “Clinical and Molecular Pharmacology of Etomidate.” Anesthesiology, vol. 114, no. 3, 2011, pp. 695–707. doi:10.1097/ALN.0b013e3181ff72b5. |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |
This is not something Australian trainees should expect to see in their exam, but it's a substance worth knowing about nonetheless |