More Bad News for Etomidate?

Written by Jason Lesnick 

Spoon Feed 
This large retrospective database study found etomidate for induction was associated with a 28% increased risk of mortality.

End of etomidate? 
This was a retrospective cohort study of 1,689,945 adult patients intubated in hospitals that utilized the Premier database from 2008-2021. The authors utilized a framework of a target trial emulation, where a hypothetical randomized trial is envisioned, then a research protocol is created to best mimic that with observational data. Patients were excluded if they were not intubated or in an ICU within the first 2 days of hospitalization, didn’t receive a paralytic on the day of intubation, received vasopressors the day before intubation, or received IV steroids on the day of intubation. The primary outcome was hospital mortality. After exclusions, 434,823 patients remained; 291,262 (67.0%) patients received etomidate and 22,273 (5.1%) received ketamine (but not etomidate). 22,273 propensity matched pairs were created among patients who received ketamine to compare to those who received etomidate. Receipt of etomidate was associated with higher risk of hospital mortality relative to ketamine – 21.6% vs 18.7%; absolute risk, 2.8% (95%CI 2.1%-3.6%); aOR 1.28 (95%CI 1.21-1.34). Multiple secondary analyses were performed, and these associations remained. Even when including steroid administration in the days after receiving etomidate, it didn’t significantly change the estimate (aHR without steroids 1.23 (95%CI 1.16-1.32) vs. with steroids 1.24 (95%CI 1.16-1.32). 

How will this change my practice?
The prior studies on this subject (EVK RCT | meta-analysis | yet another meta-analysis) and this study all found higher mortality with etomidate. These studies will cause me to use ketamine as my first-line induction agent.

Editor’s note: RSI RCT is actively recruiting. In 2027, we can settle the etomidate/ketamine debate. For now, it doesn’t look good for etomidate. But consider, PARAMEDIC3 and IVIO showed IO epinephrine was the same as IV in OHCA, despite prior observational studies concluding IO was worse. One good RCT can overrule all the observational dogma data. ~Clay Smith

Source
Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine among Critically Ill Patients. Am J Respir Crit Care Med. 2024 Nov 15;210(10):1243-1251. doi: 10.1164/rccm.202404-0813OC. PMID: 39173173