View source for Etomidate

{{Short description|Short-acting anaesthetic and sedative drug}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 457797420
| image = File:Etomidate.svg
| image_class = skin-invert-image
| caption = Above: molecular structure of (''R'')-etomidate
Below: 3D representation of an etomidate molecule
| image2 = Etomidate 3D.png
| width = 150
| alt = <!--Clinical data-->
| tradename = Amidate, Hypnomidate, Tomvi
| Drugs.com = {{drugs.com|monograph|etomidate}}
| DailyMedID = Etomidate
| routes_of_administration = [[Intravenous therapy|Intravenous]]
| ATC_prefix = N01
| ATC_suffix = AX07
| legal_AU = S4
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Summary Basis of Decision (SBD) for Tomvi | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00500&lang=en | access-date=29 May 2022}}</ref>
| legal_US = Rx-only
| legal_UK = POM

<!--Pharmacokinetic data-->| protein_bound = 76%
| metabolism = [[Ester]] [[hydrolysis]] in [[Blood plasma|plasma]] and [[liver]]
| elimination_half-life = 75 minutes
| excretion = Urine (85%) and [[Bile duct]] (15%)

<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 33125-97-2
| PubChem = 36339
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00292
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 33418
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Z22628B598
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00548
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 23731

<!--Chemical data-->| IUPAC_name = Ethyl&nbsp;3-[(1''R'')-1-phenylethyl]imidazole-<wbr>5-carboxylate
| C = 14
| H = 16
| N = 2
| O = 2
| SMILES = O=C(OCC)c1cncn1C(c2ccccc2)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C14H16N2O2/c1-3-18-14(17)13-9-15-10-16(13)11(2)12-7-5-4-6-8-12/h4-11H,3H2,1-2H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = NPUKDXXFDDZOKR-UHFFFAOYSA-N
| melting_point = 67
| boiling_point = 392
}}

'''Etomidate'''<ref>US Patent 3354173 'Imidazole carboxylates'</ref> ([[United States Adopted Name|USAN]], [[International Nonproprietary Name|INN]], [[British Approved Name|BAN]]; marketed as '''Amidate''') is a short-acting [[intravenous]] anaesthetic agent used for the induction of [[general anaesthesia]] and [[sedation]]<ref name="pmid12023700">{{cite journal | vauthors = Vinson DR, Bradbury DR | title = Etomidate for procedural sedation in emergency medicine | journal = Annals of Emergency Medicine | volume = 39 | issue = 6 | pages = 592–598 | date = June 2002 | pmid = 12023700 | doi = 10.1067/mem.2002.123695 }}</ref> 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.<ref name="Bergen">{{cite journal | vauthors = Bergen JM, Smith DC | title = A review of etomidate for rapid sequence intubation in the emergency department | journal = The Journal of Emergency Medicine | volume = 15 | issue = 2 | pages = 221–230 | year = 1998 | pmid = 9144065 | doi = 10.1016/S0736-4679(96)00350-2 }}</ref>

The most common side effects include venous pain on injection and skeletal muscle movements.<ref>{{cite web | title=Coronavirus (COVID-19) Update: December 22, 2020 | website=U.S. Food and Drug Administration | date=22 December 2020 | url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-december-22-2020 | archive-url=https://web.archive.org/web/20201222231016/http://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-december-22-2020 | url-status=dead | archive-date=December 22, 2020 | access-date=23 December 2020}} {{PD-notice}}</ref>

==Medical uses==

===Sedation and anesthesia===
In emergency settings, etomidate can be used as a [[sedative]] hypnotic agent. It is used for [[conscious sedation]]<ref>{{cite journal | vauthors = Di Liddo L, D'Angelo A, Nguyen B, Bailey B, Amre D, Stanciu C | title = Etomidate versus midazolam for procedural sedation in pediatric outpatients: a randomized controlled trial | journal = Annals of Emergency Medicine | volume = 48 | issue = 4 | pages = 433–40, 440.e1 | date = October 2006 | pmid = 16997680 | doi = 10.1016/j.annemergmed.2006.03.004 }}</ref><ref>{{cite journal | vauthors = Miner JR, Danahy M, Moch A, Biros M | title = Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department | journal = Annals of Emergency Medicine | volume = 49 | issue = 1 | pages = 15–22 | date = January 2007 | pmid = 16997421 | doi = 10.1016/j.annemergmed.2006.06.042 }}</ref> and as a part of a [[rapid sequence induction]] to induce anaesthesia.<ref name="Siv">{{cite journal | vauthors = Sivilotti ML, Filbin MR, Murray HE, Slasor P, Walls RM | title = Does the sedative agent facilitate emergency rapid sequence intubation? | journal = Academic Emergency Medicine | volume = 10 | issue = 6 | pages = 612–620 | date = June 2003 | pmid = 12782521 | doi = 10.1111/j.1553-2712.2003.tb00044.x }}</ref><ref name="Hohl">{{cite journal | vauthors = Hohl CM, Kelly-Smith CH, Yeung TC, Sweet DD, Doyle-Waters MM, Schulzer M | title = The effect of a bolus dose of etomidate on cortisol levels, mortality, and health services utilization: a systematic review | journal = Annals of Emergency Medicine | volume = 56 | issue = 2 | pages = 105–13.e5 | date = August 2010 | pmid = 20346542 | doi = 10.1016/j.annemergmed.2010.01.030 }}</ref> 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.<ref>{{cite journal | vauthors = Zed PJ, Abu-Laban RB, Harrison DW | title = Intubating conditions and hemodynamic effects of etomidate for rapid sequence intubation in the emergency department: an observational cohort study | journal = Academic Emergency Medicine | volume = 13 | issue = 4 | pages = 378–383 | date = April 2006 | pmid = 16531603 | doi = 10.1111/j.1553-2712.2006.tb00313.x | doi-access = free }}</ref><ref>{{cite journal | vauthors = Sokolove PE, Price DD, Okada P | title = The safety of etomidate for emergency rapid sequence intubation of pediatric patients | journal = Pediatric Emergency Care | volume = 16 | issue = 1 | pages = 18–21 | date = February 2000 | pmid = 10698137 | doi = 10.1097/00006565-200002000-00005 | s2cid = 24913220 }}</ref> 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.<ref name="Hohl"/> Thus, etomidate is a good induction agent for people who are hemodynamically unstable.<ref name="Siv"/> 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.<ref name="Bergen"/><ref name="Walls">{{cite book | veditors = Walls RM, Murphy MF, Schneider RE |year=2000 |title= Manual of emergency airway management}}</ref><ref>{{cite book | vauthors = Marx J |year=2002 |title=Rosen's emergency medicine: concepts and clinical practice}}</ref><ref>{{cite journal | vauthors = Wadbrook PS | title = Advances in airway pharmacology. Emerging trends and evolving controversy | journal = Emergency Medicine Clinics of North America | volume = 18 | issue = 4 | pages = 767–788 | date = November 2000 | pmid = 11130938 | doi = 10.1016/S0733-8627(05)70158-9 }}</ref><ref>{{cite journal | vauthors = Yeung JK, Zed PJ | title = A review of etomidate for rapid sequence intubation in the emergency department | journal = CJEM | volume = 4 | issue = 3 | pages = 194–198 | date = May 2002 | pmid = 17609005 | doi = 10.1017/S1481803500006370 | doi-access = free }}</ref>

In those with sepsis, one dose of the medication does not appear to affect the risk of death.<ref>{{cite journal | vauthors = Gu WJ, Wang F, Tang L, Liu JC | title = Single-dose etomidate does not increase mortality in patients with sepsis: a systematic review and meta-analysis of randomized controlled trials and observational studies | journal = Chest | volume = 147 | issue = 2 | pages = 335–346 | date = February 2015 | pmid = 25255427 | doi = 10.1378/chest.14-1012 }}</ref>

===Speech and memory test===
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 and Hospital|Montreal Neurological Institute]].<ref>{{cite journal | vauthors = Jones-Gotman M, Sziklas V, Djordjevic J | title = Intracarotid amobarbital procedure and etomidate speech and memory test | journal = The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques | volume = 36 | issue = Suppl 2 | pages = S51–S54 | date = August 2009 | pmid = 19760903 }}</ref><ref>{{cite journal | vauthors = Jones-Gotman M, Sziklas V, Djordjevic J, Dubeau F, Gotman J, Angle M, Tampieri D, Olivier A, Andermann F | display-authors = 6 | title = Etomidate speech and memory test (eSAM): a new drug and improved intracarotid procedure | journal = Neurology | volume = 65 | issue = 11 | pages = 1723–1729 | date = December 2005 | pmid = 16344513 | doi = 10.1212/01.wnl.0000187975.78433.cb | s2cid = 1835535 }}</ref> However, only [[Retrospective cohort study|retrospective cohort studies]] support the use and safety of etomidate for this test.<ref>{{cite journal | vauthors = Patel A, Wordell C, Szarlej D | title = Alternatives to sodium amobarbital in the Wada test | journal = The Annals of Pharmacotherapy | volume = 45 | issue = 3 | pages = 395–401 | date = March 2011 | pmid = 21325100 | doi = 10.1345/aph.1P476 | s2cid = 207264114 }}</ref>

===Steroidogenesis inhibitor===
In addition to its action and use as an anesthetic, etomidate has also been found to directly inhibit the [[enzymatic]] [[biosynthesis]] of [[steroid hormone]]s, including [[corticosteroid]]s in the [[adrenal gland]].<ref name="Davies2015">{{cite book| vauthors = Davies TF |title=A Case-Based Guide to Clinical Endocrinology|url=https://books.google.com/books?id=bv3NCgAAQBAJ&pg=PA11|date= 2015|publisher=Springer|isbn=978-1-4939-2059-4|pages=11–}}</ref><ref name="JamesonGroot2015">{{cite book| vauthors = Jameson JL, De Groot LJ |title=Endocrinology: Adult and Pediatric E-Book|url=https://books.google.com/books?id=xmLeBgAAQBAJ&pg=PA250|date=2015|publisher=Elsevier Health Sciences|isbn=978-0-323-32195-2|pages=250–}}</ref> As the only adrenal [[steroidogenesis inhibitor]] available for intravenous or [[parenteral administration]], it is useful in situations in which rapid control of [[hypercortisolism]] is necessary or in which [[oral administration]] is unfeasible.<ref name="Davies2015" /><ref name="JamesonGroot2015" /><ref name="pmid29203576">{{cite journal | vauthors = McGrath M, Ma C, Raines DE | title = Dimethoxy-etomidate: A Nonhypnotic Etomidate Analog that Potently Inhibits Steroidogenesis | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 364 | issue = 2 | pages = 229–237 | date = February 2018 | pmid = 29203576 | pmc = 5783534 | doi = 10.1124/jpet.117.245332 }}</ref>

==Use in executions==
The U.S. state of Florida used the drug in a [[death penalty]] procedure when [[Mark Asay|Mark James Asay]], 53, was executed on August 24, 2017. He became the first person in the U.S. to be executed with etomidate as one of the drugs. Etomidate replaces [[midazolam]] as the sedative. Drug companies have made it harder to buy midazolam for executions. The etomidate was followed by [[rocuronium bromide]], a paralytic, and finally, [[potassium acetate]] in place of the commonly used [[potassium chloride]] injection to stop the heart. Potassium acetate was first used for this purpose inadvertently in a 2015 execution in Oklahoma.<ref>{{cite news|url=http://www.sun-sentinel.com/news/florida/fl-reg-florida-execution-asay-20170824-story.html|title=Florida executes convicted killer Mark Asay using new drug| vauthors = Dearon J |newspaper=Sun Sentinel}}</ref>

==Adverse effects==
Etomidate suppresses [[corticosteroid]] synthesis in the adrenal cortex by reversibly inhibiting [[Steroid 11β-hydroxylase|11β-hydroxylase]], an enzyme important in adrenal steroid production; it leads to primary adrenal suppression.<ref>{{cite journal | vauthors = Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D | title = Inhibition of adrenal steroidogenesis by the anesthetic etomidate | journal = The New England Journal of Medicine | volume = 310 | issue = 22 | pages = 1415–1421 | date = May 1984 | pmid = 6325910 | doi = 10.1056/NEJM198405313102202 }}</ref><ref name="Archambault 270–82">{{cite journal | vauthors = Archambault P, Dionne CE, Lortie G, LeBlanc F, Rioux A, Larouche G | title = Adrenal inhibition following a single dose of etomidate in intubated traumatic brain injury victims | journal = CJEM | volume = 14 | issue = 5 | pages = 270–282 | date = September 2012 | pmid = 22967694 | doi = 10.2310/8000.2012.110560 | doi-access = free }}</ref> Using a continuous etomidate infusion for [[sedation]] of critically ill trauma patients in [[intensive care unit]]s has been associated with increased mortality due to adrenal suppression.<ref name="Led">{{cite journal | vauthors = Ledingham IM, Watt I | title = Influence of sedation on mortality in critically ill multiple trauma patients | journal = Lancet | volume = 1 | issue = 8336 | pages = 1270 | date = June 1983 | pmid = 6134053 | doi = 10.1016/S0140-6736(83)92712-5 | s2cid = 305277 }}</ref> 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.<ref name="Led"/>

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.<ref name="Hohl"/> For this reason, many authors have suggested that etomidate should never be used for critically ill patients with septic shock<ref>{{cite journal | vauthors = Morris C, McAllister C | title = Etomidate for emergency anaesthesia; mad, bad and dangerous to know? | journal = Anaesthesia | volume = 60 | issue = 8 | pages = 737–740 | date = August 2005 | pmid = 16029220 | doi = 10.1111/j.1365-2044.2005.04325.x | s2cid = 27825801 | doi-access =  }}</ref><ref>{{cite journal | vauthors = Jackson WL | title = Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock?: a critical appraisal | journal = Chest | volume = 127 | issue = 3 | pages = 1031–1038 | date = March 2005 | pmid = 15764790 | doi = 10.1378/chest.127.3.1031 }}</ref><ref name=An>{{cite journal | vauthors = Bloomfield R, Noble DW | title = Exploring the role of etomidate in septic shock and acute respiratory distress syndrome | journal = Critical Care Medicine | volume = 34 | issue = 6 | pages = 1858; author reply 1858-1858; author reply 1859 | date = June 2006 | pmid = 16715011 | doi = 10.1097/01.ccm.0000220048.38438.40 }}</ref> because it could increase mortality.<ref name="An"/><ref>{{cite journal | vauthors = Cuthbertson BH, Sprung CL, Annane D, Chevret S, Garfield M, Goodman S, Laterre PF, Vincent JL, Freivogel K, Reinhart K, Singer M, Payen D, Weiss YG | display-authors = 6 | title = The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock | journal = Intensive Care Medicine | volume = 35 | issue = 11 | pages = 1868–1876 | date = November 2009 | pmid = 19652948 | doi = 10.1007/s00134-009-1603-4 | s2cid = 24371957 }}</ref> 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.<ref name="Walls"/><ref>{{cite journal | vauthors = Murray H, Marik PE | title = Etomidate for endotracheal intubation in sepsis: acknowledging the good while accepting the bad | journal = Chest | volume = 127 | issue = 3 | pages = 707–709 | date = March 2005 | pmid = 15764747 | doi = 10.1378/chest.127.3.707 | doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, Bertrand L, Beltramini A, Gamand P, Albizzati S, Perdrizet D, Lebail G, Chollet-Xemard C, Maxime V, Brun-Buisson C, Lefrant JY, Bollaert PE, Megarbane B, Ricard JD, Anguel N, Vicaut E, Adnet F | display-authors = 6 | title = Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial | journal = Lancet | volume = 374 | issue = 9686 | pages = 293–300 | date = July 2009 | pmid = 19573904 | doi = 10.1016/S0140-6736(09)60949-1 | s2cid = 52230993 }}</ref> In addition, a recent meta-analysis done by Hohl could not conclude that etomidate increased mortality.<ref name=Hohl/> 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.<ref name="Hohl"/> Other authors<ref>{{cite journal | vauthors = den Brinker M, Joosten KF, Liem O, de Jong FH, Hop WC, Hazelzet JA, van Dijk M, Hokken-Koelega AC | display-authors = 6 | title = Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 90 | issue = 9 | pages = 5110–5117 | date = September 2005 | pmid = 15985474 | doi = 10.1210/jc.2005-1107 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Schulz-Stübner S | title = Sedation in traumatic brain injury: avoid etomidate | journal = Critical Care Medicine | volume = 33 | issue = 11 | pages = 2723; author reply 2723 | date = November 2005 | pmid = 16276231 | doi = 10.1097/01.ccm.0000187093.71107.a8 }}</ref><ref name=Stu>{{cite journal | vauthors = Stuttmann R, Allolio B, Becker A, Doehn M, Winkelmann W | title = [Etomidate versus etomidate and hydrocortisone for anesthesia induction in abdominal surgical interventions] | journal = Der Anaesthesist | volume = 37 | issue = 9 | pages = 576–582 | date = September 1988 | pmid = 3056084 }}</ref>  advise giving a prophylactic dose of steroids (e.g. [[hydrocortisone]]) if etomidate is used, but only one small prospective controlled study<ref name="Stu"/> 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]].<ref name="retro">{{cite journal |vauthors=Komatsu R, You J, Mascha EJ, Sessler DI, Kasuya Y, Turan A |date=December 2013 |title=Anesthetic induction with etomidate, rather than propofol, is associated with increased 30-day mortality and cardiovascular morbidity after noncardiac surgery |journal=Anesthesia and Analgesia |volume=117 |issue=6 |pages=1329–1337 |doi=10.1213/ANE.0b013e318299a516 |pmid=24257383 |s2cid=23165849 |doi-access=free}}</ref> People given etomidate also had significantly greater odds of having cardiovascular morbidity and significantly longer hospital stay.<ref name = retro/>  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]].<ref name="Archambault 270–82"/> 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.<ref>{{cite journal | vauthors = Daniell H | title = Opioid and benzodiazepine contributions to etomidate-associated adrenal insufficiency | journal = Intensive Care Medicine | volume = 34 | issue = 11 | pages = 2117–8 | date = November 2008 | pmid = 18795258 | doi = 10.1007/s00134-008-1264-8 | s2cid = 36288054 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Daniell HW | title = Opioid contribution to decreased cortisol levels in critical care patients | journal = Archives of Surgery | volume = 143 | issue = 12 | pages = 1147–1148 | date = December 2008 | pmid = 19075164 | doi = 10.1001/archsurg.143.12.1147 }}</ref> 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).<ref>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.</ref>

==Pharmacology==
[[File:6x3v GABAA-Rezeptorstruktur.png|thumb|Side view of the EM structure of the α1β3γ2 GABAA receptor. [[gamma-Aminobutyric acid|GABA]] and etomidate are coloured magenta. Subunits in different colours. One alpha and one beta subunit is hidden. Green chloride ions illustrated in the channel pore.<ref name="pmid32879488">{{cite journal | vauthors = Kim JJ, Gharpure A, Teng J, Zhuang Y, Howard RJ, Zhu S, Noviello CM, Walsh RM, Lindahl E, Hibbs RE | display-authors = 6 | title = Shared structural mechanisms of general anaesthetics and benzodiazepines | journal = Nature | volume = 585 | issue = 7824 | pages = 303–308 | date = September 2020 | pmid = 32879488 | pmc = 7486282 | doi = 10.1038/s41586-020-2654-5 }}</ref>]]
===Pharmacodynamics===
([[Cahn–Ingold–Prelog priority rules|''R'']])-Etomidate is tenfold more potent than its (''S'')-[[enantiomer]]. At low concentrations (''R'')-etomidate is a [[allosteric modulator|modulator]] at [[GABAA receptor|GABA<sub>A</sub>]] [[Receptor (biochemistry)|receptors]]<ref>{{cite book | vauthors = Vanlersberghe C, Camu F | title = Modern Anesthetics | chapter = Etomidate and other non-barbiturates | volume = 182 | issue = 182 | pages = 267–282 | year = 2008 | pmid = 18175096 | doi = 10.1007/978-3-540-74806-9_13 | isbn = 978-3-540-72813-9 | series = Handbook of Experimental Pharmacology | publisher = Springer }}</ref> containing β2 and β3<ref>{{cite journal | vauthors = Drexler B, Jurd R, Rudolph U, Antkowiak B | title = Distinct actions of etomidate and propofol at beta3-containing gamma-aminobutyric acid type A receptors | journal = Neuropharmacology | volume = 57 | issue = 4 | pages = 446–455 | date = September 2009 | pmid = 19555700 | doi = 10.1016/j.neuropharm.2009.06.014 | s2cid = 26796180 }}</ref> subunits. At higher concentrations, it can elicit currents in the absence of GABA and behaves as an [[allosteric modulator|allosteric agonist]]. Its [[binding site]] is located in the [[Transmembrane domain|transmembrane section]] of this receptor between the beta and alpha [[Protein subunit|subunits]] (β<sup>+</sup>α<sup>−</sup>). β3-containing GABA<sub>A</sub> 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.<ref>{{cite journal | vauthors = Chiara DC, Dostalova Z, Jayakar SS, Zhou X, Miller KW, Cohen JB | title = Mapping general anesthetic binding site(s) in human α1β3 γ-aminobutyric acid type A receptors with [³H]TDBzl-etomidate, a photoreactive etomidate analogue | journal = Biochemistry | volume = 51 | issue = 4 | pages = 836–847 | date = January 2012 | pmid = 22243422 | pmc = 3274767 | doi = 10.1021/bi201772m }}</ref>

===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.
* Onset of action: 30–60 seconds
* Peak effect: 1 minute
* Duration: 3–5 minutes; terminated by redistribution
* Distribution: V<sub>d</sub>: 2–4.5&nbsp;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<ref name="Bergen"/>

==Metabolism==
Etomidate is highly protein-bound in [[blood plasma]] and is metabolised by hepatic and plasma [[esterase]]s to inactive products. It exhibits a [[Exponential decay|biexponential decline]].{{cn|date=January 2022}}

==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,<ref>[https://www.who.int/medicines/publications/druginformation/innlists/RL06.pdf International Non-Proprietary Names for Pharmaceutical Preparations – Rec. I.N.N. List 6]</ref> but the ''R'' form is substantially more active than its [[enantiomer]].<ref>{{cite book |title= Anesthetic Pharmacology: Basic Principles and Clinical Practice |edition= 2nd | veditors = Evers AS, Maze M, Kharasch ED |publisher= Cambridge University Press |year= 2011 |chapter= Chapter 27. Pharmacokinetics of intravenous anesthetics | vauthors = Servin FS, Sear JW }}</ref> It was later reformulated as a single-enantiomer drug, becoming the first general anesthetic in that class to be used clinically.<ref>{{cite journal | vauthors = Tomlin SL, Jenkins A, Lieb WR, Franks NP | title = Stereoselective effects of etomidate optical isomers on gamma-aminobutyric acid type A receptors and animals | journal = Anesthesiology | volume = 88 | issue = 3 | pages = 708–717 | date = March 1998 | pmid = 9523815 | doi = 10.1097/00000542-199803000-00022 | s2cid = 11665790 | doi-access = free }}</ref>

== Use as recreational drug==
Etomidate has been made into an [[e-cigarette liquid]] known as '''space oil''' ({{Lang-zh|太空油}}) in Hong Kong<ref name=":1"/> or '''kpod''' in Singapore.<ref name=sg>{{cite web | url=https://www.moh.gov.sg/newsroom/deterrence-for-use-of-kpods-or-vape-juices-mixed-with-etomidate | title=Deterrence for Use of Kpods or Vape Juices Mixed with Etomidate |publisher=[[Ministry of Health (Singapore)|Ministry of Health of Singapore]] |date=8 January 2025 }}</ref> It may also be mixed with other drugs, including [[cannabis]] and [[ketamine]].<ref name=":0">{{Cite press release |title=LCQ7: Combating vaping of "space oil" |url=https://www.info.gov.hk/gia/general/202410/23/P2024102300363.htm |access-date=2025-01-15 |publisher=[[Government of Hong Kong Special Administrative Region]] |date=2024-10-23}}</ref><ref name=":1">{{Cite web |title=Narcotics Division, Security Bureau - Space Oil Drug |url=https://www.nd.gov.hk/en/space_oil_drug.html |access-date=2025-01-15 |publisher=Narcotics Division of the [[Security Bureau (Hong Kong)|Security Bureau]] |language=en}}</ref>

=== 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.<ref>{{Cite news |title=Customs seizes suspected space oil, and illicit cigarettes at West Kowloon Station |url=https://www.thestandard.com.hk/breaking-news/fc/4/224501/Customs-seizes-suspected-space-oil,-and-illicit-cigarettes-at-West-Kowloon-Station |date=2025-01-06 |access-date=2025-01-15 |work=[[The Standard (Hong Kong)|The Standard]] |language=en}}</ref> 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.<ref name=":0" /><ref>{{Cite news | vauthors = Wang W, Lam E |date=2025-01-14 |title='Space oil' to be classed as a controlled drug from February 14 |url=https://www.thestandard.com.hk/section-news/section/50044298/269381/'Space-oil'-to-be-classed-as-a-controlled-drug-from-February-14https://www.thestandard.com.hk/section-news/section/50044298/269381/'Space-oil'-to-be-classed-as-a-controlled-drug-from-February-14 |work=The Standard}}</ref>

===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.<ref name=sg/>

== References ==
{{reflist}}

== Further reading ==
{{refbegin|30em}}
* {{cite journal | vauthors = Cotton BA, Guillamondegui OD, Fleming SB, Carpenter RO, Patel SH, Morris JA, Arbogast PG | title = Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients | journal = Archives of Surgery | volume = 143 | issue = 1 | pages = 62–7; discussion 67 | date = January 2008 | pmid = 18209154 | doi = 10.1001/archsurg.143.1.62 | doi-access =  }}; discussion 67.
* {{cite journal | vauthors = den Brinker M, Hokken-Koelega AC, Hazelzet JA, de Jong FH, Hop WC, Joosten KF | title = One single dose of etomidate negatively influences adrenocortical performance for at least 24h in children with meningococcal sepsis | journal = Intensive Care Medicine | volume = 34 | issue = 1 | pages = 163–168 | date = January 2008 | pmid = 17710382 | pmc = 2668631 | doi = 10.1007/s00134-007-0836-3 }}
* {{cite journal | vauthors = Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W, Keh D, Briegel J, Beishuizen A, Dimopoulou I, Tsagarakis S, Singer M, Chrousos GP, Zaloga G, Bokhari F, Vogeser M | display-authors = 6 | title = Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine | journal = Critical Care Medicine | volume = 36 | issue = 6 | pages = 1937–1949 | date = June 2008 | pmid = 18496365 | doi = 10.1097/CCM.0b013e31817603ba | collaboration = American College of Critical Care Medicine | s2cid = 7861625 }}
* {{cite journal | vauthors = Mullins ME, Theodoro DL | title = Lack of evidence for adrenal insufficiency after single-dose etomidate | journal = Archives of Surgery | volume = 143 | issue = 8 | pages = 808–9; author reply 809 | date = August 2008 | pmid = 18711047 | doi = 10.1001/archsurg.143.8.808-c }}; author reply 809.
* {{cite journal | vauthors = Sacchetti A | title = Etomidate: not worth the risk in septic patients | journal = Annals of Emergency Medicine | volume = 52 | issue = 1 | pages = 14–16 | date = July 2008 | pmid = 18565379 | doi = 10.1016/j.annemergmed.2008.01.001 }}
* {{cite journal | vauthors = Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J | display-authors = 6 | title = Hydrocortisone therapy for patients with septic shock | journal = The New England Journal of Medicine | volume = 358 | issue = 2 | pages = 111–124 | date = January 2008 | pmid = 18184957 | doi = 10.1056/NEJMoa071366 | doi-access = free | hdl = 2078.1/200895 | hdl-access = free }}
* {{cite journal | vauthors = Tekwani KL, Watts HF, Chan CW, Nanini S, Rzechula KH, Kulstad EB | title = The effect of single-bolus etomidate on septic patient mortality: a retrospective review | journal = The Western Journal of Emergency Medicine | volume = 9 | issue = 4 | pages = 195–200 | date = November 2008 | pmid = 19561744 | pmc = 2672284 }}
* {{cite journal | vauthors = Tekwani KL, Watts HF, Rzechula KH, Sweis RT, Kulstad EB | title = A prospective observational study of the effect of etomidate on septic patient mortality and length of stay | journal = Academic Emergency Medicine | volume = 16 | issue = 1 | pages = 11–14 | date = January 2009 | pmid = 19055676 | doi = 10.1111/j.1553-2712.2008.00299.x | doi-access = free }}
* {{cite journal | vauthors = Vinclair M, Broux C, Faure P, Brun J, Genty C, Jacquot C, Chabre O, Payen JF | display-authors = 6 | title = Duration of adrenal inhibition following a single dose of etomidate in critically ill patients | journal = Intensive Care Medicine | volume = 34 | issue = 4 | pages = 714–719 | date = April 2008 | pmid = 18092151 | doi = 10.1007/s00134-007-0970-y | s2cid = 23538535 }}
{{Refend}}

== External links ==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/etomidate | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Etomidate }}

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