Open Access Articles- Top Results for Etomidate


Systematic (IUPAC) name
ethyl 3-[(1R)-1-phenylethyl]imidazole-
Clinical data
Trade names Amidate, Hypnomidate
AHFS/ monograph
  • US: C (Risk not ruled out)
Pharmacokinetic data
Protein binding 76%
Metabolism Ester hydrolysis in plasma and liver
Half-life 75 minutes
Excretion Urine (85%) and biliary (15%)
33125-97-2 7pxY
PubChem CID 36339
DrugBank DB00292 7pxY
ChemSpider 33418 7pxY
UNII Z22628B598 7pxY
KEGG D00548 7pxY
Chemical data
Formula C14H16N2O2
244.289 g/mol
Physical data
Boiling point Script error: No such module "convert".
 14pxY (what is this?)  (verify)

Etomidate (USAN, INN, BAN) (marketed as Amidate) is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation[1] for short procedures such as reduction of dislocated joints, tracheal intubation, and cardioversion. It was discovered at Janssen Pharmaceutica in 1964 and was introduced as an intravenous agent in 1972 in Europe and in 1983 in the United States.[2]

Medical uses

In emergency settings, etomidate was one of the most frequently used sedative hypnotic agents. It is used for conscious sedation[3][4] and as a part of a rapid sequence induction to induce anaesthesia.[5][6] It is used as an anaesthetic agent since it has a rapid onset of action and a safe cardiovascular risk profile, and therefore is less likely to cause a significant drop in blood pressure than other induction agents.[7][8] In addition, etomidate is often used because of its easy dosing profile, limited suppression of ventilation, lack of histamine liberation and protection from myocardial and cerebral ischemia.[6] Thus, etomidate is a good induction agent for people who are hemodynamically unstable.[5] Etomidate also has interesting characteristics for people with traumatic brain injury because it is one of the only anesthetic agents able to decrease intracranial pressure and maintain a normal arterial pressure.[2][9][10][11][12]

In those with sepsis, one dose of the medication does not appear to affect the risk of death.[13]

Another use for etomidate is to determine speech lateralization in people prior to performing lobectomies to remove epileptogenic centres in the brain. This is called the etomidate speech and memory test, or eSAM, and is used at the Montreal Neurological Institute.[14][15] However, only retrospective cohort studies support the use and safety of etomidate for this test.[16]

Adverse effects

Etomidate suppresses corticosteroid synthesis in the adrenal cortex by reversibly inhibiting 11-beta-hydroxylase, an enzyme important in adrenal steroid production; it leads to primary adrenal suppression.[17][18] Using a continuous etomidate infusion for sedation of critically ill trauma patients in intensive care units has been associated with increased mortality due to adrenal suppression.[19] Continuous intravenous administration of etomidate leads to adrenocortical dysfunction. The mortality of patients exposed to a continuous infusion of etomidate for more than 5 days increased from 25% to 44%, mainly due to infectious causes such as pneumonia.[19]

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.[6] For this reason, many authors have suggested that etomidate should never be used for critically ill patients with septic shock[20][21][22] because it could increase mortality.[22][23] 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.[9][24] 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.[25] In addition, a recent meta-analysis done by Hohl could not conclude that etomidate increased mortality.[6] 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.[6] Other authors[26][27][28] advise giving a prophylactic dose of steroids (e.g. hydrocortisone) if etomidate is used, but only one small prospective controlled study[28] 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 2.5-fold increase in the risk of dying than those given propofol.[29] People given etomidate also had significantly greater odds of having cardiovascular morbidity and significantly longer hospital stay.[29] These results, especially given the large size of study, strongly suggest that, at the very least, clinicians should use etomidate judiciously.[29]

In people with traumatic brain injury, etomidate use is associated with a blunting of an ACTH stimulation test.[18] 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.[30][31] However, only retrospective evidence of this effect exists and prospective studies are needed to measure the clinical impact of this interaction.



Etomidate is a modulator at GABAA receptors[32] containing β3 subunits.[33]


At the typical dose, anesthesia is induced for 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.

  • Onset of action: 30–60 seconds
  • Peak effect: 1 minute
  • Duration: 3–5 minutes; terminated by redistribution
  • Distribution: Vd: 2-4.5 l/kg
  • Protein binding: 76%
  • Metabolism: Hepatic and plasma esterases
  • Half-life distribution: 2.7 minutes
  • Half-life redistribution: 29 minutes
  • Half-life elimination: 2.9 to 5.3 hours[2]


Etomidate is highly protein-bound in blood plasma and is metabolised by hepatic and plasma esterases to inactive products. It exhibits a biexponential decline.


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,[citation needed] but the dextrorotatory form (the structure having R chirality) is substantially more active than its enantiomer.[34] It was later reformulated as a single-enantiomer drug, becoming the first general anesthetic in that class to be used clinically.[35]


Etomidate is prepared by the following procedure. It illustrates a special case of obtaining derivatives of imidazole by interaction of α-aminocarbonyl compounds with thiocyanates. The reaction of α-methylbenzylamine with ethyl chloroacetate gives N-ethoxycarbonylmethyl-N-1-phenylethylamine, which undergoes further formylation by formic acid. The resulting N-ethoxycarbonylmethyl-N-formyl-N-1-phenylethylamine undergoes further C-formylation by ethyl formate in the presence of sodium ethoxide. The product is further processed (without being isolated) by a solution of potassium thiocyanate in hydrochloric acid. As a result of the reaction of thiocyanate ions with the amino group which occurs as a result of acidic hydrolysis of the N-formamide protecting group and further interaction of the obtained intermediate with the newly inserted aldehyde group, a Marckwald reaction type heterocyclization takes place, resulting in formation of 5-ethoxycarbonyl-2-mercapto-1-(1-phenylethyl)imidazole. Finally, the thiol group is removed by oxidative dethionation upon interaction with a mixture of nitric and nitrous acids (nitric acid in the presence of sodium nitrite), which evidently occurs through formation of unstable sulfinic acid, which easily loses sulfur dioxide resulting the desired etomidate.

File:Etomidate synthesis.png
Etomidate synthesis:[36] C.A.M.V. Eijken, F.E. Godefroi, U.S. Patent 3,354,173 (1967).


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