In emergency settings, etomidate is one of the most frequently used sedative hypnotic agents. It is used for conscious sedation and as a part of a rapid sequence induction to induce anaesthesia. 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. 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. Thus, etomidate is an ideal induction agent for patients who are hemodynamically unstable. Etomidate also has interesting characteristics for patients with traumatic brain injury because it is one of the only anesthetic agents able to decrease intracranial pressure and maintain a normal arterial pressure.
Another use for etomidate is to determine speech lateralization in patients 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. However, there exists only retrospective cohort studies supporting the use and safety of etomidate for this test. Etomidate is injected into the carotid artery and will anesthetize the ipsilateral brain hemisphere for 5–10 minutes. During such time, rudimentary speech and memory tasks are performed in order to determine if removal of a particular part of a hemisphere will affect the patients language abilities or induce severe memory impairments. eSAM is done on patients who show impairments on both verbal and non-verbal learning and memory test during the basic examination or if there is evidence of bitemporal abnormalities in EEG and/or MRI. This procedure is also done on all left-handed or ambidextrous patients because 30% of left-handed or ambidextrous patients have either right hemispheric speech dominance or bilateral speech representation. Prior to the procedure the patient is shown a series of objects and during the procedure shown another series of objects. Once the injection has worn off, the patient is shown some of the same objects and asked whether or not they saw them that day. If the patient doesn't recognize the objects that were shown during the procedure, it is clear that the medial temporal structures that were left un-anesthetized during the procedure are not functioning properly.
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. 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. This effect was demonstrated in a landmark study in 1983 by Ledingham and Watt. They showed that 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 like pneumonia.
Because of etomidate-induced adrenal suppression, the use of etomidate 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 haemodynamic 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 that more studies were needed because of lack of statistical power to conclude definitively about the effect of etomidate on mortality. Thus, Hohl suggests that the burden of proof is to prove that etomidate is safe for use in septic patients and that more research is needed before etomidate 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 2.5-fold increase in the risk of dying than those given propofol. People given etomidate also had significantly greater odds of having cardiovascular morbidity and significantly longer hospital stay. These results, especially given the large size of study, strongly suggest that, at the very least, clinicians should use etomidate judiciously.
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, there is only retrospective evidence of this effect and prospective studies are needed to measure the clinical impact of this interaction.
At the typical dose, anesthesia is induced for about 5–10 minutes even though the half-life of drug metabolism is approximately 75 minutes. This is 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
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.
^ abcdeHohl, CM; Kelly-Smith, CH; Yeug, TC; Sweet, DD; Doyle-Waters, MM; Schulzer, M (2010). "The effect of a bolus dose of etomidate on cortisol levels, mortality, and health services utilization: a systematic review". Ann Emerg Med56 (2): 105–113. doi:10.1016/j.annemergmed.2010.01.030. PMID20346542.
^Zed, PJ; Abu-Laban, RB; Harrison, DW. (2006). "Intubating conditions and hemodynamic effects of etomidate for rapid sequence intubation in the emergency department: an observational cohort study". Acad Emerg Med.13 (4): 378–83. doi:10.1111/j.1553-2712.2006.tb00313.x. PMID16531603.
^Yeung, JK; Zed, PJ (2002). "A review of etomidate for rapid sequence intubation in the emergency department". CJEM4 (3): 194–198. PMID17609005.
^Jones-Gotman, M; Sziklas, V; Djordjevic, J (2009). "Intracarotid amobarbital procedure and etomidate speech and memory test". Can J Neurol Sci. 36 Suppl 2: S51–4. PMID19760903.
^Jones-Gotman, M; Sziklas, V; Djordjevic, J; Dubeau, F; Gotman, J; Angle, M; Tampieri, D; Olivier, A; Andermann, F (2005). "Etomidate speech and memory test (eSAM): a new drug and improved intracarotid procedure". Neurology65 (11): 1723–1729. doi:10.1212/01.wnl.0000187975.78433.cb. PMID16344513.
^Patel, Akta; Wordell, Cindy; Szarlej, Dorota (2011). "Alternatives to sodium amobarbital in the Wada test". Ann Pharmacother45 (3): 395–401. doi:10.1345/aph.1P476. PMID21325100.
^Wagner, RL; White, PF; Kan, PB; Rosenthal, MH; Feldman, D. (1984). "Inhibition of adrenal steroidogenesis by the anesthetic etomidate". N Engl J Med.310 (22): 1415–21. doi:10.1056/NEJM198405313102202. PMID6325910.
^ abArchambault, P; Dionne, CE; Lortie, G; LeBlanc, F; Rioux, A; Larouche, G (September 2012). "Adrenal inhibition following a single dose of etomidate in intubated traumatic brain injury victims.". CJEM14 (5): 270–82. PMID22967694.
^Jackson, WL (2005). "Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock? A critical appraisal". Chest127 (3): 1031–1038. doi:10.1378/chest.127.3.1031. PMID15764790.
^ abAnnane, D; Sebille, V; Bellissant, E (2006). "Exploring the role of etomidate in septic shock and acute respiratory distress syndrome". Crit Care Med34 (6): 1858–1859. doi:10.1097/01.ccm.0000220048.38438.40.
^Cuthbertson, BH; Sprung, CL; Annane, D; Chevret, S; Garfield, M; Goodman, S; Laterre, PF; Vincent, JL et al. (2009). "The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock". Intensive Care Med35 (1): 1868–1876. doi:10.1007/s00134-009-1603-4. PMID19652948.|displayauthors= suggested (help)
^Jabre, P; Combes, X; Laposttolle, F; Dhaouadi, M; Ricard-Hibon, A; Vivien, B; Bertrand, L; Beltramini, A et al. (2009). "Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomized controlled trial". Lancet374 (9686): 293–300. doi:10.1016/S0140-6736(09)60949-1. PMID19573904.
^Den Brinker, M; Joosten, KF; Liem, O; de Jong, FH; Hop, WC; Hazelzet, JA; van Dijk, M; Hokken-Koelega, AC. (2005). "Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality". J Clin Endocrinol Metab90 (9): 5110–7. doi:10.1210/jc.2005-1107. PMID15985474.
^Schulz-Stubner, S (2005). "Sedation in traumatic brain injury: Avoid etomidate". Crit Care Med33 (11): 2723.
^ abStuttmann, R; Allolio, B; Becker, A (1988). "etomidate versus etomidate and hydrocortisone for anesthesia induction in abdominal surgical interventions". Anaesthesist37 (9): 576=582.
^ abcKomatsu, R; You, J; Mascha, EJ; Sessler, DI; Kasuya, Y; Turan, A (December 2013). "Anesthetic induction with etomidate, rather than propofol, is associated with increased 30-day mortality and cardiovascular morbidity after noncardiac surgery.". Anesthesia and Analgesia117 (6): 1329–37. doi:10.1213/ANE.0b013e318299a516. PMID24257383.
^Daniell, Harry (2008). "Opioid and benzodiazepine contributions to etomidate-associated adrenal insufficiency". Intensive Care Medicine34 (11): 2117–8. doi:10.1007/s00134-008-1264-8.
^Drexler, B; Jurd, R; Rudolph, U; Antkowiak, B (2009). "Distinct actions of etomidate and propofol at beta3-containing gamma-aminobutyric acid type A receptors". Neuropharmacology57 (4): 446–55. doi:10.1016/j.neuropharm.2009.06.014. PMID19555700.
^Servin, Frédérique S.; Sear, John W. (2011). "Chapter 27. Pharmacokinetics of intravenous anesthetics". In Evers, Alex S.; Maze, Mervyn; Kharasch, Evan D. Anesthetic Pharmacology: Basic Principles and Clinical Practice (2nd ed.). Cambridge University Press.
^Tomlin, Sarah L.; Jenkins, Andrew; Lieb, William R.; Franks, Nicholas P. (1998). "Stereoselective Effects of Etomidate Optical Isomers on Gamma‐aminobutyric Acid Type A Receptors and Animals". Anesthesiology88 (3): 708–717. PMID9523815.
Cotton, B. A.; Guillamondegui, O. D.; Fleming, S. B.; Carpenter, R. O.; Patel, S. H.; Morris, J. A.; Arbogast, P. G. (2008). "Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients". Arch Surg143 (1): 62–7. doi:10.1001/archsurg.143.1.62.; discussion 67.
Marik, P. E.; Pastores, S. M.; Annane, D.; Meduri, G. U.; Sprung, C. L.; Arlt, W.; Keh, D.; Briegel, J. et al. (2008). "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". Crit Care Med36 (6): 1937–49. doi:10.1097/CCM.0b013e31817603ba. PMID18496365.
Mullins, M. E.; Theodoro, D. L. (2008). "Lack of evidence for adrenal insufficiency after single-dose etomidate". Arch Surg143 (8): 808–9. doi:10.1001/archsurg.143.8.808-c.; author reply 809.
Sprung, C. L.; Annane, D.; Keh, D.; Moreno, R.; Singer, M.; Freivogel, K.; Weiss, Y. G.; Benbenishty, J. et al. (2008). "Hydrocortisone therapy for patients with septic shock". N Engl J Med358 (2): 111–24. doi:10.1056/NEJMoa071366. PMID18184957.
Tekwani, K.; Watts, H.; Chan, C.; Rzechula, K.; Nanini, S.; Kulstad, E. (2008). "The effect of single-bolus etomidate on septic patient mortality: a retrospective review". West J of Emerg Med9 (4): 195–200.
Tekwani, K. L.; Watts, H. F.; Rzechula, K. H.; Sweis, R. T.; Kulstad, E. B. (2009). "A prospective observational study of the effect of etomidate on septic patient mortality and length of stay". Acad Emerg Med16 (1): 11–4. doi:10.1111/j.1553-2712.2008.00299.x. PMID19055676.
Vinclair, M.; Broux, C.; Faure, P.; Brun, J.; Genty, C.; Jacquot, C.; Chabre, O.; Payen, J. F. (2008). "Duration of adrenal inhibition following a single dose of etomidate in critically ill patients". Intensive Care Med34 (4): 714–9. doi:10.1007/s00134-007-0970-y. PMID18092151.