Etomidate

Etomidate is a short-acting intravenous general anaesthetic, a carboxylated imidazole, chemically unrelated to other anaesthetics, used mainly to induce anaesthesia. It is chiral and given as the single active (R)-(+)-enantiomer, which is about ten times more potent than the (S)-form. Its defining clinical advantage is haemodynamic stability: it causes little of the fall in blood pressure seen with propofol or thiopental, so it is favoured for rapid-sequence induction in shock, trauma or cardiac-risk patients (marketed as Amidate and Hypnomidate). Like propofol and the barbiturates, etomidate is a positive allosteric modulator of the GABA-A receptor, enhancing GABA-gated chloride currents to produce sedation and unconsciousness. At higher concentrations it can open the channel directly. It is unusually selective for receptors containing β2 and β3 subunits, binding a transmembrane pocket at the β+/α− subunit interface: the single β3-N265M point mutation almost abolishes its anaesthetic action in mice, and β3-containing receptors mediate the hypnotic/immobilising effect while β2 receptors contribute sedation. Because it acts at low-micromolar concentrations rather than binding a receptor with nanomolar affinity, there is no meaningful nanomolar binding table for it. Etomidate's most important adverse effect is adrenocortical suppression: it potently and reversibly inhibits 11β-hydroxylase (CYP11B1), the final enzyme in cortisol synthesis, so that even a single induction dose can suppress cortisol production for roughly 24–72 hours. This was discovered after continuous ICU sedation infusions were linked to increased mortality (largely infection-related), which led to infusions being abandoned. The risk–benefit of even single-dose use in critically ill or septic patients is still debated. Other characteristic effects are myoclonus on induction, pain on injection, and a notably high rate of postoperative nausea and vomiting. After an IV bolus etomidate acts within 30–60 seconds and wears off in about 3–5 minutes as it redistributes. It is ~76% protein-bound and is rapidly broken down by hepatic and plasma esterases (ester hydrolysis) to an inactive carboxylic acid, with an elimination half-life of a few hours. Long thought to have little abuse potential, since around 2021 etomidate has become a novel recreational drug in East Asia: vaped in e-cigarette liquids sold as 'space oil' (Hong Kong), 'kpod' (Singapore) or 'zombie' cartridges (Taiwan), often mixed with designer analogues (metomidate, etomidate-CF3 and others) and adulterants: prompting emergency drug-control scheduling in Hong Kong, Singapore and Taiwan in 2025–2026.