title: Etomidate as an induction agent in septic patients: red flags or false alarms?
abstract: Despite its widespread use in North America and many other parts of the world, the safety of etomidate as an induction agent for rapid sequence intubation in septic patients is still debated. In this article, we evaluate the current literature on etomidate, review its clinical history, and discuss the controversy regarding its use, especially in sepsis. We address eight questions: (i) When did concern over the safety of etomidate first arise? (ii) What is the mechanism by which etomidate is thought to affect the adrenal axis? (iii) How has adrenal insufficiency in relation to etomidate use been defined or identified in the literature? (iv) What is the evidence that single dose etomidate is associated with subsequent adrenal-cortisol dysfunction? (v) What is the clinical significance of adrenal insufficiency or dysfunction associated with single dose etomidate, and where are the data that support or refute the contention that single-dose etomidate is associated with increased mortality or important post emergency department (ED) clinical outcomes? (vi) How should etomidate's effects in septic patients best be measured? (vii) What are alternative induction agents and what are the advantages and disadvantages of these agents relative to etomidate? (viii) What future work is needed to further clarify the characteristics of etomidate as it is currently used in patients with sepsis? We conclude that the observational nature of almost all available data suggesting adverse outcomes from etomidate does not support abandoning its use for rapid sequence induction. However, because we see a need to balance theoretical harms and benefits in the presence of data supporting the non-inferiority of alternative agents without similar theoretical risks associated with them, we suggest that the burden of proof to support continued widespread use may rest with the proponents of etomidate. We further suggest that practitioners become familiar with the use of more than one agent while awaiting further definitive data.
authors.affiliation: Advocate Christ Medical Center, Department of Emergency Medicine, Oak Lawn, IL.
authors.forename: Erik B
authors.initials: EB
authors.lastname: Kulstad
authors.forename: Ejaaz A
authors.initials: EA
authors.lastname: Kalimullah
authors.forename: Karis L
authors.initials: KL
authors.lastname: Tekwani
authors.forename: D Mark
authors.initials: DM
authors.lastname: Courtney
references.citation: Crit Care Med. 2008 Jun;36(6):1937-49
references.pmid: 18496365
references.citation: Chest. 2007 Dec;132(6):2054
references.pmid: 18079246
references.citation: J Clin Endocrinol Metab. 2005 Sep;90(9):5110-7
references.pmid: 15985474
references.citation: Arch Int Pharmacodyn Ther. 1982 Apr;256(2):308-10
references.pmid: 7103618
references.citation: Br J Anaesth. 1985 Feb;57(2):156-9
references.pmid: 2982387
references.citation: Lancet. 2009 Jul 25;374(9686):293-300
references.pmid: 19573904
references.citation: Circulation. 2007 Oct 16;116(16):1855-63
references.pmid: 17893277
references.citation: CJEM. 2006 Sep;8(5):347-50
references.pmid: 17338847
references.citation: JAMA. 2002 Aug 21;288(7):862-71
references.pmid: 12186604
references.citation: Emerg Med J. 2004 Nov;21(6):655-9
references.pmid: 15496686
references.citation: Intensive Care Med. 2009 Nov;35(11):1868-76
references.pmid: 19652948
references.citation: Acad Emerg Med. 2008 Apr;15(4):377-83
references.pmid: 18370994
references.citation: N Engl J Med. 2008 Jan 10;358(2):111-24
references.pmid: 18184957
references.citation: Crit Care Med. 2005 Nov;33(11):2723; author reply 2723
references.pmid: 16276231
references.citation: Lancet. 1982 Jun 19;1(8286):1414-5
references.pmid: 6123706
references.citation: Crit Care Med. 2005 Jun;33(6):1392-9
references.pmid: 15942361
references.citation: J Trauma. 2008 Sep;65(3):573-9
references.pmid: 18784570
references.citation: Crit Care Med. 2007 Apr;35(4):1012-8
references.pmid: 17334243
references.citation: Intensive Care Med. 2008 Apr;34(4):714-9
references.pmid: 18092151
references.citation: Crit Care. 2006;10(4):161
references.pmid: 16941756
references.citation: Arch Surg. 2008 Jan;143(1):62-7; discussion 67
references.pmid: 18209154
references.citation: Ann Emerg Med. 2008 Jul;52(1):14-6
references.pmid: 18565379
references.citation: Resuscitation. 2008 Aug;78(2):105-6
references.pmid: 18620110
references.citation: Br Med J (Clin Res Ed). 1983 Dec 17;287(6408):1835-7
references.pmid: 6322902
references.citation: Anesthesiology. 1992 Apr;76(4):564-72
references.pmid: 1550282
references.citation: Ann Emerg Med. 2007 Aug;50(2):200-1; author reply 201-2
references.pmid: 17643856
references.citation: Acad Emerg Med. 2003 Apr;10(4):329-38
references.pmid: 12670846
references.citation: N Engl J Med. 1984 May 31;310(22):1415-21
references.pmid: 6325910
references.citation: Anaesth Intensive Care. 1997 Jun;25(3):255-9
references.pmid: 9209606
references.citation: Lancet. 1983 Feb 26;1(8322):484
references.pmid: 6131207
references.citation: Intensive Care Med. 2008 Jan;34(1):163-8
references.pmid: 17710382
references.citation: Chest. 2006 Oct;130(4):941-6
references.pmid: 17035422
references.citation: Prehosp Emerg Care. 2001 Apr-Jun;5(2):163-8
references.pmid: 11339727
references.citation: J Intensive Care Med. 2007 May-Jun;22(3):157-65
references.pmid: 17562739
references.citation: J Trauma. 2009 Jul;67(1):45-50
references.pmid: 19590307
references.citation: West J Emerg Med. 2008 Nov;9(4):195-200
references.pmid: 19561744
references.citation: Acad Emerg Med. 2001 Jan;8(1):1-7
references.pmid: 11136139
references.citation: Chest. 2005 Mar;127(3):707-9
references.pmid: 15764747
references.citation: Crit Care Med. 1983 Sep;11(9):730-4
references.pmid: 6884053
references.citation: Ann Emerg Med. 2008 Jul;52(1):13-4
references.pmid: 18565378
references.citation: Am J Emerg Med. 1994 Jul;12(4):425-8
references.pmid: 8031425
references.citation: Anaesthesia. 2009 May;64(5):532-9
references.pmid: 19413824
references.citation: Crit Care. 2007;11(3):R56
references.pmid: 17506873
references.citation: Anesthesiology. 1995 Feb;82(2):367-76
references.pmid: 7856895
references.citation: Br Med J (Clin Res Ed). 1984 Feb 11;288(6415):485-6
references.pmid: 6318881
references.citation: Br J Anaesth. 2006 Jul;97(1):116-7
references.pmid: 16769703
references.citation: Arch Surg. 2008 Aug;143(8):808-9; author reply 809
references.pmid: 18711047
references.citation: Crit Care. 2006;10(4):R105
references.pmid: 16859529
references.citation: Chest. 2005 Mar;127(3):1031-8
references.pmid: 15764790
references.citation: Anaesthesia. 2005 Aug;60(8):737-40
references.pmid: 16029220
references.citation: Emerg Med J. 2004 Nov;21(6):700-2
references.pmid: 15496697
references.citation: Crit Care Resusc. 2004 Jun;6(2):123-9
references.pmid: 16566699
references.citation: Acad Emerg Med. 2009 Jan;16(1):11-4
references.pmid: 19055676
references.citation: Lancet. 1983 Jun 4;1(8336):1270
references.pmid: 6134053
references.citation: Intensive Care Med. 2005 Mar;31(3):388-92
references.pmid: 15703896
references.citation: Anaesthesia. 1984 Oct;39(10):973-81
references.pmid: 6496912