Etomidate

Why this drug is interesting

Etomidate induces anaesthesia without meaningfully depressing the myocardium or dropping the systemic vascular resistance. In a shocked patient — the patient for whom propofol is most dangerous — that is a substantial advantage, and it is the entire reason the drug survives.

It also inhibits 11β-hydroxylase, the enzyme that converts 11-deoxycortisol to cortisol. This is not a rare idiosyncratic reaction; it is a predictable pharmacological action that occurs after a single induction dose in essentially everyone. The argument for two decades has been whether that biochemical fact translates into harm.

Dosing

• Adults and children: 0.3 mg/kg intravenously at induction, which "gives sleep lasting from 4 to 5 minutes"¹
• Elderly: 0.15–0.2 mg/kg — roughly half the adult dose, "further adjusted according to the individual patient response and to clinical effects"¹
• Do not exceed a total of 30 mL (3 ampoules) per procedure
• "Dosage should be adjusted to the individual patient response and to clinical effects"
• In children under 15 years the dose may need to be increased — "a supplementary dose of up to 30% of the normal dose for adults is sometimes necessary to obtain the same depth and duration of sleep as obtained in adults"¹

Etomidate has no analgesic properties. As with propofol, an opioid such as fentanyl is generally co-administered for intubation, and a neuromuscular blocking agent is required for rapid sequence induction.

The adrenal question

So the SmPC does three things: it acknowledges the effect after a single dose, it raises steroid supplementation as an option rather than a requirement, and it counsels caution — not contraindication — in sepsis.

How the evidence sits

• The biochemical effect is not in dispute. Cortisol synthesis is measurably suppressed for hours after a single induction dose.
• The clinical consequence is. Randomised trials of single-dose etomidate for emergency intubation have generally not demonstrated a mortality difference, while consistently confirming the adrenal effect.
• Observational data in sepsis have repeatedly suggested harm, and are equally repeatedly confounded — the sickest patients are the ones most likely to be given the most haemodynamically stable induction agent, which biases the comparison against etomidate in exactly the wrong direction.
• No trial has resolved it definitively, and the question has largely been settled in practice by the wider availability of ketamine as an alternative stable induction agent rather than by data.

Pharmacology

Mechanism

Etomidate is a carboxylated imidazole that potentiates GABA-A receptor function. It has minimal effect on sympathetic tone or baroreceptor function, which is why blood pressure is preserved. It reduces cerebral metabolic rate, cerebral blood flow and intracranial pressure while maintaining mean arterial pressure — so, unlike propofol, it tends to preserve cerebral perfusion pressure.

Kinetics

Onset

One arm–brain circulation

Duration of sleep after 0.3 mg/kg

4–5 minutes

Offset

By redistribution

Metabolism

Hepatic and plasma ester hydrolysis to inactive metabolites

Adverse effects

• Adrenocortical suppression — the defining issue
• Myoclonus at induction — common, sometimes marked, and easily mistaken for a seizure. It is not epileptiform and is reduced by opioid pre-medication
• Pain on injection — common with the propylene glycol formulation, which is what Hypnomidate is (its label declares 3626 mg of propylene glycol per 10 mL); the B.Braun lipid emulsion presentation reduces it
• Nausea and vomiting — more frequent than with propofol
• Respiratory depression and apnoea
• Hiccup and cough

Practical use in the ED

The realistic choice at an emergency induction in a shocked patient is between etomidate, ketamine, and a substantially reduced dose of propofol.

1. Resuscitate before you induce, whichever agent you choose.
2. Have a vasopressor immediately available regardless of agent.
3. Warn the team about myoclonus if using etomidate, so it is not misread as seizure activity or as inadequate anaesthesia.
4. Do not use it for maintenance, and do not give repeated doses.
5. Consider whether steroid supplementation is warranted in a septic patient who received it — the label raises this, and it is a reasonable conversation with critical care rather than an automatic action.

Critical appraisal

1. The controversy conflates two very different exposures. The excess mortality that started it came from continuous infusions for ICU sedation. Applying that finding to a single induction dose is a substantial extrapolation, and one that the trial evidence has not supported.
2. Absence of a demonstrated mortality difference is not proof of safety, particularly for an outcome that would require a very large trial to detect. Both the drug's defenders and its critics tend to overstate what the neutral trials establish.
3. The confounding runs in a specific direction and is rarely acknowledged. Observational comparisons systematically allocate the sickest patients to etomidate. Any analysis that does not address this is not evidence about the drug.
4. Practice has moved without the question being answered. Wider use of ketamine has reduced how often the etomidate decision arises at all — which is a reasonable way to sidestep an unresolved argument, but should not be mistaken for having resolved it.
5. Myoclonus is under-warned. It is startling to a team that has not seen it, and there are reports of it prompting unnecessary anticonvulsant treatment.

References

1. 1
   Hypnomidate 2 mg/ml Injection — Summary of Product Characteristics, Piramal Critical Care. electronic Medicines Compendium. Sections 4.2, 4.4, 4.8. Verified 24 Aug 2026. Compare B.Braun Etomidate 2 mg/ml emulsion, emc.
2. 2
   Jabre P, Combes X, Lapostolle F, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients (KETASED): a multicentre randomised controlled trial. Lancet 2009;374(9686):293–300. PubMed
3. 3
   Annane D. ICU physicians should abandon the use of etomidate! Intensive Care Med 2005;31(3):325–6. PubMed
4. 4
   Royal College of Anaesthetists and Difficult Airway Society. NAP4: Major complications of airway management in the United Kingdom. nationalauditprojects.org.uk
5. 5
   Etomidate — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk