Product Code Database
EtomidateUS Patent 3354173 'Imidazole carboxylates' (USAN, INN, BAN; marketed as Amidate) is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation for short procedures such as reduction of dislocated joints, tracheal intubation, cardioversion and electroconvulsive therapy. It was developed at Janssen Pharmaceutica in 1964 and was introduced as an intravenous agent in 1972 in Europe and in 1983 in the United States.
The most common side effects include venous pain on injection and skeletal muscle movements.
In those with sepsis, one dose of the medication does not appear to affect the risk of death.
Because of etomidate-induced adrenal suppression, its use for patients with sepsis is controversial. Cortisol levels have been reported to be suppressed up to 72 hours after a single bolus of etomidate in this population at risk for adrenal insufficiency. For this reason, many authors have suggested that etomidate should never be used for critically ill patients with septic shock because it could increase mortality. However, other authors continue to defend etomidate's use for septic patients because of etomidate's safe hemodynamic profile and lack of clear evidence of harm. A study by Jabre et al. showed that a single dose of etomidate used for Rapid Sequence Induction prior to endrotracheal intubation has no effect on mortality compared to ketamine even though etomidate did cause transient adrenal suppression. In addition, a recent meta-analysis done by Hohl could not conclude that etomidate increased mortality. The authors of this meta-analysis concluded more studies were needed because of lack of statistical power to conclude definitively about the effect of etomidate on mortality. Thus, Hohl suggests a burden to prove etomidate is safe for use in septic patients, and more research is needed before it is used. Other authors advise giving a prophylactic dose of steroids (e.g. hydrocortisone) if etomidate is used, but only one small prospective controlled study in patients undergoing colorectal surgery has verified the safety of giving stress dose corticosteroids to all patients receiving etomidate.
In a retrospective review of almost 32,000 people, etomidate, when used for the induction of anaesthesia, was associated with a 2.5-fold increase in the risk of dying compared with those given propofol. People given etomidate also had significantly greater odds of having cardiovascular morbidity and significantly longer hospital stay. Given the retrospective design of this study, it is difficult to draw any firm conclusions from the data.
In people with traumatic brain injury, etomidate use is associated with a blunting of an ACTH stimulation test. The clinical impact of this effect has yet to be determined.
In addition, concurrent use of etomidate with opioids and/or benzodiazepines, is hypothesized to exacerbate etomidate-related adrenal insufficiency. However, only retrospective evidence of this effect exists and prospective studies are needed to measure the clinical impact of this interaction.
Etomidate is associated with a high incidence of burning on injection, postoperative nausea and vomiting, and superficial thrombophlebitis (with rates higher than propofol).Kosarek L, et al. Increase in Venous Complications Associated With Etomidate Use During a Propofol Shortage: An Example of Clinically Important Adverse Effects Related to Drug Substitution. The Ochsner Journal. 2011;11:143-146.
Pharmacology
Pharmacodynamics
( R)-Etomidate is tenfold more potent than its ( S)-enantiomer. At low concentrations ( R)-etomidate is a modulator at GABAA receptor receptors (2025). 9783540728139, Springer. ISBN 9783540728139 containing β2 and β3 subunits. At higher concentrations, it can elicit currents in the absence of GABA and behaves as an allosteric agonist. Its binding site is located in the transmembrane section of this receptor between the beta and alpha Protein subunit (β+α−). β3-containing GABAA receptors are involved in the anesthetic actions of etomidate, while the β2-containing receptors are involved in some of the sedation and other actions that can be elicited by this drug.
Pharmacokinetics
At the typical dose, anesthesia is induced for the duration of about 5–10 minutes, though the half-life of drug metabolism is about 75 minutes, because etomidate is redistributed from the plasma to other tissues.
Metabolism
Etomidate is highly protein-bound in blood plasma and is metabolised by hepatic and plasma to inactive products. It exhibits a biexponential decline.
Formulation
Etomidate is usually presented as a clear colourless solution for injection containing 2 mg/mL of etomidate in an aqueous solution of 35% propylene glycol, although a lipid emulsion preparation (of equivalent strength) has also been introduced. Etomidate was originally formulated as a racemic mixture, International Non-Proprietary Names for Pharmaceutical Preparations – Rec. I.N.N. List 6 but the R form is substantially more active than its enantiomer. It was later reformulated as a single-enantiomer drug, becoming the first general anesthetic in that class to be used clinically.
Use as recreational drug
Etomidate has been made into an e-cigarette liquid known as space oil (太空油) in Hong Kong or kpod in Singapore. It may also be mixed with other drugs, including cannabis and ketamine.
Hong Kong
Etomidate is regulated as Part 1 poison under the Pharmacy and Poisons Regulations (Cap. 138A), which states that possessing etomidate without provisions is punishable by a fine of up to HK$100,000 and imprisonment for two years. Due to the increasing imports of space oil, the 2024 Policy Address has stated that the control of etomidate will be tightened. Etomidate is classed as a controlled drug on 14 February 2025 by the Dangerous Drugs Ordinance (Cap. 134), which states that illegal possession or smoking, inhaling, ingesting and injecting space oil is liable to a maximum penalty of imprisonment of seven years and a fine of HK$1,000,000, while trafficking or illegal importing etomidate is liable to a maximum penalty of life imprisonment and a fine of HK$5,000,000.
Singapore
In Singapore, etomidate is classified as a poison under the Poisons Act. Sellers can be sentenced to imprisonment for up to two years and/or fined up to $10,000.
Further reading
External links
Categories: 11β-hydroxylase Inhibitors, Belgian Inventions, Chemical Substances For Emergency Medicine, Cholesterol Side-chain Cleavage Enzyme Inhibitors, Cyp17a1 Inhibitors, Ethyl Esters, Gabaa Receptor Positive Allosteric Modulators, General Anesthetics, Glycine Receptor Agonists, Imidazoles, Janssen Pharmaceutica, Lethal Injection Components
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