Etomidate: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
CheMoBot (talk | contribs)
Bots
141,565 edits
Updating {{drugbox}} (changes to watched fields) per Chem/Drugbox validation (report errors or bugs)
Line 61: Line 61:


==Adverse effects==
==Adverse effects==
Etomidate suppresses [[corticosteroid]] synthesis in the adrenal cortex by reversibly inhibiting [[Steroid 11-beta-hydroxylase|11-beta-hydroxylase]], an enzyme important in adrenal steroid production; it leads to primary adrenal suppression.<ref>{{cite journal | doi = 10.1056/NEJM198405313102202 | last1 = Wagner | first1 = RL | last2 = White | first2 = PF | last3 = Kan | first3 = PB | last4 = Rosenthal | first4 = MH | last5 = Feldman | first5 = D. | year = 1984 | title = Inhibition of adrenal steroidogenesis by the anesthetic etomidate | url = | journal = N Engl J Med. | volume = 310 | issue = 22| pages = 1415–21 | pmid = 6325910 }}</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. This effect was demonstrated in a landmark study in 1983 by Ledingham and Watt.<ref name="Led">{{cite journal|last1=Ledingham|first1=IM|last2=Watt|first2=I|year=1983|title=Influence of sedation in critically ill multiple trauma patients|journal=Lancet|volume=1|page=1270|pmid=6134053|doi=10.1016/S0140-6736(83)92712-5|issue=8336}}</ref> They showed that continuous intravenous administration of etomidate leads to adrenocortical dysfunction.
Etomidate suppresses [[corticosteroid]] synthesis in the adrenal cortex by reversibly inhibiting [[Steroid 11-beta-hydroxylase|11-beta-hydroxylase]], an enzyme important in adrenal steroid production; it leads to primary adrenal suppression.<ref>{{cite journal | doi = 10.1056/NEJM198405313102202 | last1 = Wagner | first1 = RL | last2 = White | first2 = PF | last3 = Kan | first3 = PB | last4 = Rosenthal | first4 = MH | last5 = Feldman | first5 = D. | year = 1984 | title = Inhibition of adrenal steroidogenesis by the anesthetic etomidate | url = | journal = N Engl J Med. | volume = 310 | issue = 22| pages = 1415–21 | pmid = 6325910 }}</ref> <ref>{{cite journal|last=Archambault|first=P|coauthors=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|date=2012 Sep|volume=14|issue=5|pages=270-82|pmid=22967694}}</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. This effect was demonstrated in a landmark study in 1983 by Ledingham and Watt.<ref name="Led">{{cite journal|last1=Ledingham|first1=IM|last2=Watt|first2=I|year=1983|title=Influence of sedation in critically ill multiple trauma patients|journal=Lancet|volume=1|page=1270|pmid=6134053|doi=10.1016/S0140-6736(83)92712-5|issue=8336}}</ref> 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.<ref name="Led"/>
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.<ref name="Led"/>


Revision as of 03:21, 10 October 2013

Etomidate
Clinical data
AHFS/Drugs.comMonograph
Pregnancy
category
  • D (United States)
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
  • UK: POM (Prescription only)
Pharmacokinetic data
Protein binding75%
MetabolismEster hydrolysis
Elimination half-life75 minutes
ExcretionRenal (85%) and biliary (15%)
Identifiers
  • ethyl 3-[(1R)-1-phenylethyl]imidazole-
    5-carboxylate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.046.700 Edit this at Wikidata
Chemical and physical data
FormulaC14H16N2O2
Molar mass244.289 g/mol g·mol−1
3D model (JSmol)
Boiling point392 °C (738 °F)
  • O=C(OCC)c1cncn1C(c2ccccc2)C
  • InChI=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 checkY
  • Key:NPUKDXXFDDZOKR-UHFFFAOYSA-N checkY
  (verify)

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

Drug class

Etomidate is a carboxylated imidazole derivative that has anesthetic and amnestic properties, but that has no analgesic properties.[citation needed]

Medical uses

In emergency settings, etomidate is one of the most frequently used sedative hypnotic agents. It is used by physicians 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 an ideal induction agent for patients who are haemodynamically unstable.[5] 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.[2][9][10][11][12][13]

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.[14][15] However, there exists only retrospective cohort studies supporting the use and safety of etomidate for this test.[16] 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.

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. This effect was demonstrated in a landmark study in 1983 by Ledingham and Watt.[19] 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.[19]

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.[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 haemodynamic 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 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.[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 addition, concurrent use of etomidate with opioids and/or benzodiazepines, is hypothesized to exacerbate etomidate related adrenal insufficiency.[29][30] However, there is only retrospective evidence of this effect and prospective studies are needed to measure the clinical impact of this interaction.

Aside from the adrenal suppression caused by etomidate, seizure-like activity is occasionally seen with anesthetic induction with etomidate. In the absence of concurrent EEG monitoring, it is difficult to ascribe this to cortical activity. Myoclonic movement originating at the spinal cord level is often a likely mechanism. Excitatory phenomena, and epileptiform movements and EEG activity may be observed during induction. Etomidate consistently increases the amplitude of somatosensory evoked potentials (in contrast to most anaesthetic agents).

Etomidate in the propylene glycol formulation may produce pain on injection, a side effect which is less likely with the lipid formulation.

There is a 30-fold difference between the effective dose and the lethal dose of etomidate, making it an extremely safe agent.

Post operative vomiting is more common than with other induction agents.

As a facilitated intubation drug, etomidate must be pushed very slowly. If is pushed too quickly, etomidate can cause trismus, making endotracheal intubation impossible. This can only be reversed by a paralytic such as succinylcholine.

Dosage

The anaesthetic induction dose for adult humans is 0.3 mg/kg intravenously, with a typical dose ranging from 20–40 mg. Etomidate causes loss of consciousness after one arm-brain circulation time. In very brief procedures such as cardioversion, a 10 mg dose may be used which may be repeated for effect.

DOSING: ADULTS — Anesthesia: I.V.: Initial: 0.2-0.6 mg/kg over 30–60 seconds for induction of anesthesia; maintenance: 5-20 µg/kg/minute except for patients in sepsis or critically ill at risk of adrenal insufficiency (see side effects).

DOSING: PEDIATRIC – For children > 10 years: Refer to adult dosing.

DOSING: GERIATRIC – Refer to adult dosing.[31][32][33]

Pharmacology

Pharmacodynamics

Etomidate is a modulator at GABAA receptors[34] containing β3 subunits.[35]

Pharmacokinetics

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
  • 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]

Metabolism

Etomidate is highly protein bound in blood plasma and is metabolised by hepatic and plasma esterases to inactive products. It exhibits a bi-exponential 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 is presented as a racemic mixture, but only the D-isomer has pharmacological activity.

Chemistry

Etomidate is prepared by the following procedure.[36][37] 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.

References

  1. ^ Vinson DR, Bradbury DR (2002). "Etomidate for procedural sedation in emergency medicine". Ann Emerg Med. 39 (6): 592–8. doi:10.1067/mem.2002.123695. PMID 12023700. {{cite journal}}: Unknown parameter |month= ignored (help)
  2. ^ a b c Bergen, JM; Smith, DC (1998). "A review of etomidate for rapid sequence intubation in the emergency department". J Emerg Med. 15 (2): 221–230. doi:10.1016/S0736-4679(96)00350-2. PMID 9144065.
  3. ^ Di Liddo, L; D’Angelo, A; Nguyen, B; Bailey, B; Amre, D; Stanciu, C (2006). "Etomidate versus midazolam for procedural sedation in pediatric outpatients: a randomized controlled trial". Ann Emerg Med. 48 (4): 433–440. doi:10.1016/j.annemergmed.2006.03.004. PMID 16997680.
  4. ^ Miner, JR; Danahy, M; Moch, A; Biros, M (2007). "Randomized clinical trial of etomidate versus propofol for procedural sedation in the emergency department". Ann Emerg Med. 49 (1): 15–22. doi:10.1016/j.annemergmed.2006.06.042. PMID 16997421.
  5. ^ a b Sivilotti, ML; Filbin, MF; Murray, HE; Slasor, P; Walls, RM; Near, Investigators (2003). "Does the sedative agent facilitate emergency rapid sequence intubation?". Acad Emerg Med. 10 (6): 612–620. doi:10.1197/aemj.10.6.612. PMID 12782521.
  6. ^ a b c d e Hohl, 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 Med. 56 (2): 105–113. doi:10.1016/j.annemergmed.2010.01.030. PMID 20346542.
  7. ^ 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. PMID 16531603.
  8. ^ Sokolove, PE; Price, DD; Okada, P. (2000). "The safety of etomidate for emergency rapid sequence intubation of pediatric patients". Pediatr Emerg Care. 16 (1): 18–21. doi:10.1097/00006565-200002000-00005. PMID 10698137.
  9. ^ a b Walls, RM; Murphy, MF; Schneider, RE (2000). "Manual of emergency airway management". {{cite journal}}: Cite journal requires |journal= (help)
  10. ^ Marx, J (2002). "Rosen's emergency medicine: concepts and clinical practice". {{cite journal}}: Cite journal requires |journal= (help)
  11. ^ Giese, JL; Stanley, TH (1983). "Etomidate: a new intravenous anesthetic induction agent". Pharmacotherapy. 3 (5): 251–258. PMID 6359080.
  12. ^ Wadbrook, PS (2000). "Advances in airway pharmacology. Emerging trends and evolving controversy". Emerg Med Clin North Am. 18 (4): 767–788. doi:10.1016/S0733-8627(05)70158-9. PMID 11130938.
  13. ^ Yeung, JK; Zed, PJ (2002). "A review of etomidate for rapid sequence intubation in the emergency department". CJEM. 4 (3): 194–198. PMID 17609005.
  14. ^ 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. PMID 19760903.
  15. ^ 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". Neurology. 65 (11): 1723–1729. doi:10.1212/01.wnl.0000187975.78433.cb. PMID 16344513.
  16. ^ Patel, Akta; Wordell, Cindy; Szarlej, Dorota (2011). "Alternatives to sodium amobarbital in the Wada test". Ann Pharmacother. 45 (3): 395–401. doi:10.1345/aph.1P476. PMID 21325100.
  17. ^ 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. PMID 6325910.
  18. ^ Archambault, P (2012 Sep). "Adrenal inhibition following a single dose of etomidate in intubated traumatic brain injury victims". CJEM. 14 (5): 270–82. PMID 22967694. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  19. ^ a b Ledingham, IM; Watt, I (1983). "Influence of sedation in critically ill multiple trauma patients". Lancet. 1 (8336): 1270. doi:10.1016/S0140-6736(83)92712-5. PMID 6134053.
  20. ^ Morris, C; McAllister, C (2005). "Etomidate for emergency anaesthesia; mad, bad and dangerous to know?". Anaesthesia. 60 (8): 737–740. doi:10.1111/j.1365-2044.2005.04325.x. PMID 16029220.
  21. ^ Jackson, WL (2005). "Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock? A critical appraisal". Chest. 127 (3): 1031–1038. doi:10.1378/chest.127.3.1031. PMID 15764790.
  22. ^ a b Annane, D; Sebille, V; Bellissant, E (2006). "Exploring the role of etomidate in septic shock and acute respiratory distress syndrome". Crit Care Med. 34 (6): 1858–1859.
  23. ^ Cuthbertson, BH; Sprung, CL; Annane, D; Chevret, S; Garfield, M; Goodman, S; Laterre, PF; Vincent, JL; Freivogel, K (2009). "The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock". Intensive Care Med. 35 (1): 1868–1876. doi:10.1007/s00134-009-1603-4. PMID 19652948. {{cite journal}}: Unknown parameter |frist10= ignored (help)
  24. ^ Murray, H; Marik, PE (2005). "Etomidate for endotracheal intubation in sepsis: acknowledging the good while accepting the bad". Chest. 127 (3): 707–709. doi:10.1378/chest.127.3.707. PMID 15764747.
  25. ^ Jabre, P; Combes, X; Laposttolle, F; Dhaouadi, M; Ricard-Hibon, A; Vivien, B; Bertrand, L; Beltramini, A; Gamand, P (2009). "Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomized controlled trial". Lancet. 374 (9686): 293–300. doi:10.1016/S0140-6736(09)60949-1. PMID 19573904.
  26. ^ 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 Metab. 90 (9): 5110–7. doi:10.1210/jc.2005-1107. PMID 15985474.
  27. ^ Schulz-Stubner, S (2005). "Sedation in traumatic brain injury: Avoid etomidate". Crit Care Med. 33 (11): 2723.
  28. ^ a b Stuttmann, R; Allolio, B; Becker, A (1988). "etomidate versus etomidate and hydrocortisone for anesthesia induction in abdominal surgical interventions". Anaesthesist. 37 (9): 576=582.
  29. ^ Daniell, Harry (2008). "Opioid and benzodiazepine contributions to etomidate-associated adrenal insufficiency". Intensive Care Medicine. 34 (11): 2117–8. doi:10.1007/s00134-008-1264-8.
  30. ^ Daniell, HW (2008). "Opioid contribution to decreased cortisol levels in critical care patients". Arch Surg. 143 (12): 1147–1148. doi:10.1001/archsurg.143.12.1147. PMID 19075164.
  31. ^ Template:Cite article
  32. ^ Template:Cite article
  33. ^ Hildreth, AN; Mejia, VA; Maxwell, RA; Smith, PW; Dart, BW; Barker, DE (2008). "Adrenal suppression following a single dose of etomidate for rapid sequence induction: a prospective rendomized study". J Trauma. 65 (3): 573–579. doi:10.1097/TA.0b013e31818255e8. PMID 18784570.
  34. ^ Vanlersberghe, C; Camu, F (2008). "Etomidate and other non-barbiturates". Handbook of experimental pharmacology. Handbook of Experimental Pharmacology. 182 (182): 267–82. doi:10.1007/978-3-540-74806-9_13. ISBN 978-3-540-72813-9. PMID 18175096.
  35. ^ Drexler, B; Jurd, R; Rudolph, U; Antkowiak, B (2009). "Distinct actions of etomidate and propofol at beta3-containing gamma-aminobutyric acid type A receptors". Neuropharmacology. 57 (4): 446–55. doi:10.1016/j.neuropharm.2009.06.014. PMID 19555700.
  36. ^ C.A.M.V. Eijken, F.E. Godefroi, U.S. patent 3,354,173 (1967)
  37. ^ P.A.J. Janssen, C.G.E. Niemegeers, K.H. Lschllekens, F.M. Lenaerts, Arzneim Forsch., 21, 1234(1971)
  • 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 Surg. 143 (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.; Beishuizen, A.; 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 Med. 36 (6): 1937–49. doi:10.1097/CCM.0b013e31817603ba. PMID 18496365. {{cite journal}}: Explicit use of et al. in: |first9= (help)
  • Mullins, M. E.; Theodoro, D. L. (2008). "Lack of evidence for adrenal insufficiency after single-dose etomidate". Arch Surg. 143 (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.; Kalenka, A.; et al. (2008). "Hydrocortisone therapy for patients with septic shock". N Engl J Med. 358 (2): 111–24. doi:10.1056/NEJMoa071366. PMID 18184957. {{cite journal}}: Explicit use of et al. in: |first9= (help)
  • 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 Med. 9 (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 Med. 16 (1): 11–4. doi:10.1111/j.1553-2712.2008.00299.x. PMID 19055676.
  • 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 Med. 34 (4): 714–9. doi:10.1007/s00134-007-0970-y. PMID 18092151.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Etomidate&oldid=576534890"