"Etomidate is the agent you choose when the heart cannot tolerate a fall in pressure — the most cardiostable induction there is. Its shadow is the adrenal gland: even one dose blunts cortisol synthesis, and in the septic patient that matters."
Tanya's notes, triangulated with Miller's Anesthesia; Morgan & Mikhail's Clinical Anesthesiology; Stoelting's Pharmacology.An imidazole, non-barbiturate hypnotic
Etomidate is an imidazole derivative and a non-barbiturate IV induction agent, hydrophobic at physiological pH. To improve solubility it is formulated in 35% propylene glycol (a 0.2% solution) or, in newer preparations, a lipid emulsion (which reduces pain on injection and thrombophlebitis). It has hypnotic and sedative — but no analgesic — action.
Ester hydrolysis to an inactive metabolite
| Parameter | Value |
|---|---|
| Initial distribution t½ | ~2.7 min |
| Redistribution t½ | ~29 min |
| Elimination t½ | 2.9–5.3 h |
| Protein binding | ~75% |
Metabolised by hepatic ester hydrolysis → etomidate carboxylic acid (inactive); excreted in urine and bile.
| Group | Change | Dose |
|---|---|---|
| Cirrhosis | Vd doubled, clearance ~normal, elimination t½ roughly twice | Titrate |
| Elderly | Smaller Vd, ↓ clearance | Reduce |
GABA-A hypnosis with cerebral protection
Acts on the GABA-A receptor to produce hypnosis: it enhances the receptor's response to GABA (so less GABA is needed) and, allosterically, can directly activate the channel. Hypnotic dose ≈ 0.3 mg/kg.
| Cerebral parameter | Effect |
|---|---|
| CBF | ↓ ~34% |
| CMRO₂ | ↓ ~45% |
| ICP | ↓ (temporary; a long-lasting fall needs a high infusion rate) |
| CPP | Maintained or increased (because MAP is unchanged) |
| MAP | No change |
| EEG | ↓ BIS; ↑ activity in epileptogenic foci — may provoke grand-mal seizures (used for intra-operative seizure-focus mapping) |
Brief stimulation, then apnoea
- Induction dose → brief hyperventilation → apnoea → ↑ PaCO₂ and a fall in PaO₂.
- The ventilatory response to a low PaO₂ is depressed.
- Overall respiratory depression is less than with propofol or thiopentone.
The most stable induction
- No effect on the sympathetic nervous system and minimal effect on myocardial contractility.
- Mild α₂/β effects with vasoconstriction → BP maintained (may slightly rise).
- Haemodynamically stable; myocardial O₂ supply–demand ratio preserved.
The defining drawback
11β-hydroxylase inhibition
Etomidate reversibly inhibits 11β-hydroxylase → ↓ cortisol synthesis → adrenocortical suppression. The concentration needed to suppress the adrenal is far lower than that needed for hypnosis — so even a single induction dose suppresses cortisol.
Avoid infusions; consider glucocorticoid supplementation where the axis is stressed. It is a particular concern in sepsis, and is an independent risk factor for adverse outcome in the critically ill — weigh the cardiovascular benefit against transient adrenal suppression.
Induction for the fragile circulation
- Induction where haemodynamic stability is paramount: CABG, valve surgery, PTCA, aortic-aneurysm and thoracic surgery, giant-aneurysm clipping.
- ↓ ICP while maintaining CPP / coronary perfusion pressure.
- Haemodynamically unstable trauma; short-term sedation.
- In ECT — can prolong seizures (useful when adequate seizure duration is hard to achieve).
Myoclonus, PONV and the adrenal
- Myoclonus — from disinhibition of extrapyramidal motor activity; reduced by pre-treatment with a benzodiazepine (midazolam) or magnesium.
- High incidence of PONV.
- Pain on injection (propylene glycol) and thrombophlebitis; histamine release.
- Adrenocortical suppression (see above); an independent risk factor for emergence delirium.
Novel etomidate derivatives
| Analogue | Feature |
|---|---|
| MOC-etomidate (methoxycarbonyl-) | Ultra-short (soft-drug, esterase-metabolised → MOC-ECA); does not inhibit adrenal steroidogenesis |
| Carboetomidate | No adrenal suppression; longer duration |
| CPMM / ABP-700 (cyclopropyl-MOC-metomidate) | No apnoea, no adrenocortical suppression; dose-dependent tachycardia/↑BP; myoclonus |
High-yield one-liners
Q: Why is etomidate cardiostable?
No sympathetic effect and minimal myocardial depression → MAP unchanged.
Q: Enzyme it inhibits?
11β-hydroxylase → ↓ cortisol → adrenal suppression (even one dose).
Q: How does it help the brain?
↓ CBF (~34%) and ↓ CMRO₂ (~45%) with MAP unchanged → CPP preserved/increased.
Q: Commonest bothersome side effect on induction & its remedy?
Myoclonus — pre-treat with midazolam (or magnesium).
Q: Metabolism?
Hepatic ester hydrolysis → etomidate carboxylic acid (inactive).
References
- Dr. Tanya. Induction Agents — handwritten viva notes (primary source for this node).
- Gropper MA, Cohen NH, Eriksson LI, et al. (eds). Miller's Anesthesia. 9th ed. Elsevier; 2020.
- Butterworth JF, Mackey DC, Wasnick JD. Morgan & Mikhail's Clinical Anesthesiology. 7th ed. McGraw-Hill; 2022.
- Flood P, Rathmell JP, Urman RD. Stoelting's Pharmacology & Physiology in Anesthetic Practice. 6th ed. Wolters Kluwer; 2022.