The debate surrounding the use of etomidate in sepsis has been going on since the 1980s and continues to plague contemporary literature. Those muddy waters were recently stirred when a meta-analysis in Critical Care Medicine concluded higher rates of adrenal insufficiency and increased mortality associated with its use1. This is not the first meta-analysis to have made such a claim2. We could spend our time debating the statistical merits of a meta-analysis, but we’d be missing the forest for the trees.

What is clear is that repetitive doses of etomidate are associated with increased mortality and adrenal suppression3. Single doses of etomidate are associated with short-term adrenal suppression that are refractory to steroid supplementation4-7. What is not clear is the clinical effect of this short-term suppression, but there is concern that it’s detrimental. There has been no trial adequately powered to answer the question and it’s likely there never will be. There are too many variables to attempt to control for – have you ever met a critically ill septic patient that has had more than one confounding process going on at the same time? Individual studies have shown a higher mortality but none were adequately powered to give us a definitive answer8,9.

Perhaps we can agree that this controversy will not be easily settled. Thus, we need to address why so many emergency physicians continue holding on to etomidate with a white-knuckle grip. Many critically ill patients lack hemodynamic stability, which is the primary reason etomidate has remained a favored induction agent compared to drugs like midazolam or propfol. If etomidate was the only hemodynamically neutral agent we had to choose from, that argument might hold some legitimacy. However, that is clearly not the case. We have an induction agent that provides that hemodynamic support along with several other properties that make it as good, if not better, than etomidate. My personal favorite happens to be ketamine.

Ketamine provides similar intubating conditions to etomidate with similar hemodynamic stability8,10. The two agents have virtually identical onset times. The safety profile of ketamine is unrivaled and “overdose” is virtually impossible11. It has been shown to be safe for use in patients of all ages, including the elderly8,12. Ketamine inhibits the re-uptake of catecholamines, and the resulting sympathomimetic effect produces mild to moderate increase in blood pressure, pulse rate and cardiac output13. These effects may actually be beneficial in the critically ill patient. So, not only do we have an agent that provides us with similar intubating conditions and similar hemodynamic support, no literature to date has demonstrated any harmful effects associated with ketamine use in sepsis.

Much of what we do in medicine is based on something other than clear cut prospective data, and many of the treatments that do have a proven mortality benefit are based on very small differences in very large trials. Just ask your neighborhood cardiologist. Many decisions we make on a daily basis are based on what the evidence suggests despite lack of a clear cut answer – is anyone still reaching for dopamine over norepinephrine for septic shock or epinephrine over albuterol for asthma? I would venture to guess that most of you answered “no” because best available evidence suggests otherwise despite clear proof. The same logic should be employed in using etomidate in sepsis when we have an alternative agent.

All of that aside, ketamine has something that etomidate doesn’t – analgesia. Patient surveys have demonstrated that many patients remember their intubation in the ED as one of the most painful things they have ever experienced14. Ketamine provides our patients with the analgesia necessary for having a tube rammed down their throat. Additionally, properly dosed ketamine has a longer duration of action providing patients the amnesia and analgesia during the post-intubation valley while vents are being setup and drips are being hung (especially important if you reached for rocuronium).

With all this controversy and the availability of an alternative agent with similar – possibly better – induction properties, why do we continue to reach for etomidate? It’s time we let it go – your next critically ill septic patient will thank you for it.

Steven Schauer, MD Resident Physician, PGY-3; CPT U.S. Army, San Antonio Military Medical Center

Etomidate References // CON
1. Chan, C.M., A.L. Mitchell, and A.F. Shorr, Etomidate is associated with mortality and adrenal insufficiency in sepsis: a meta-analysis*. Crit Care Med, 2012. 40(11): p. 2945-53.
2. Albert, S.G., S. Ariyan, and A. Rather, The effect of etomidate on adrenal function in critical illness: a systematic review. Intensive Care Med, 2011. 37(6): p. 901-10.
3. Watt, I. and I.M. Ledingham, Mortality amongst multiple trauma patients admitted to an intensive therapy unit. Anaesthesia, 1984. 39(10): p. 973-81.
4. Hildreth, A.N., et al., Adrenal suppression following a single dose of etomidate for rapid sequence induction: a prospective randomized study. J Trauma, 2008. 65(3): p. 573-9.
5. Schenarts, C.L., J.H. Burton, and R.R. Riker, Adrenocortical dysfunction following etomidate induction in emergency department patients. Acad Emerg Med, 2001. 8(1): p. 1-7.
6. Absalom, A., D. Pledger, and A. Kong, Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia, 1999. 54(9): p. 861-7.
7. O’Leary, E., et al., Etomidate and the osteocalcin response to gynaecological surgery. Br J Anaesth, 1999. 83(3): p. 461-3.
8. Jabre, P., et al., Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet, 2009. 374(9686): p. 293-300.
9. Tekwani, K.L., et al., A comparison of the effects of etomidate and midazolam on hospital length of stay in patients with suspected sepsis: a prospective, randomized study. Ann Emerg Med, 2010. 56(5): p. 481-9.
10. Ballow, S.L., et al., A standardized rapid sequence intubation protocol facilitates airway management in critically injured patients. J Trauma Acute Care Surg, 2012. 73(6): p. 1401-5.
11. Green, S.M., et al., Inadvertent ketamine overdose in children: clinical manifestations and outcome. Ann Emerg Med, 1999. 34(4 Pt 1): p. 492-7.
12. Green, S.M., et al., Intramuscular ketamine for pediatric sedation in the emergency department: safety profile in 1,022 cases. Ann Emerg Med, 1998. 31(6): p. 688-97.
13. Green, S.M., et al., Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med, 2011. 57(5): p. 449-61.
14. Kimball, D., et al., Rapid Sequence Intubation from the Patient’s Perspective. West J Emerg Med, 2011. 12(4): p. 365-7.

The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Brooke Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, Department of Defense or the U.S. Government.



# Ketamine over EtomidateHandtevy 2013-04-03 04:42
The strength of this counterpoint is in the elevation of Ketamine to where it belongs in the consideration of an induction agent. As a PEM physician who uses Ketamine frequently for procedural sedation, I agree that the added analgesic effect combined with the longer duration of action make Ketamine an ideal agent for induction. I have seen too many physicians simply forget to provide post intubation sedation and analgesia in the paralyzed pediatric patient. Ketamine mitigates this issue in the immediate post-intubation period. Great debate......My vote goes to Schauer & Pfaff
# RNCorrina Garcia 2013-05-20 01:28
Great points... But I'm still trying to figure out the difference between Tylenol & Motrin..???.. (Scratching my head). Haha I kid, I kid. As a Pedi ER RN, I appreciate the time & attention put into this important research. Well done, gentlemen. Kudos!!!

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