Key Result

There is a high probability that etomidate increases mortality when used as an induction agent in critically ill patients.

• Primary Outcome: All-cause mortality
  • Etomidate increased mortality at the main timepoint defined by trial authors in 23 percent versus comparator 20 percent; NNH 31; risk ratio = 1.16 (95 percent confidence interval [CI], 1.01 to 1.33; P=0.03)
• Secondary Outcome: Adrenal insufficiency
  • Etomidate increased development of adrenal insufficiency in 21 percent versus comparator 10 percent; risk ratio=2.01 (95 percent CI, 1.59 to 2.56, P<0.001)

EBM Commentary

1. Risk of Bias: Five studies were graded as having a low risk of bias, five had some concerns, and one was graded high-risk. The majority (57 percent) of patients included in the trials were in open-label studies. Another 24 percent of the patients included in the SRMA came from a single-blinded trial. This large lack of masking could have introduced bias into the results, which increases the uncertainty of the results.
2. Mortality Outcome: There was a wide range of time points for all-cause mortality (24 hours to 30 days). The primary outcome for the SRMA was all-cause mortality at the main time point defined by the trial, which did demonstrate a statistically significant increase with etomidate use. However, if you include the secondary outcome of 28-day all-cause mortality data from the Matchett trial, which represented 30 percent of the SRMA data, the statistical difference is lost (RR, 1.07 [95 percent CI, 0.95 to 1.21]).
3. Diversity of Patients: These were patients from a variety of settings including out-of-hospital, ED, and intensive care unit. There was also a diversity of critically ill medical and surgical patients. Some patients had more cardiovascular morbidities than other patients. This might make the results more generalizable but could also mean that the results do not apply to the individual patient presenting to the emergency department.

Bottom Line

There remains uncertainty whether using etomidate as an induction agent increases mortality in critically ill adult ED patients requiring emergent endotracheal intubation.

Case Resolution

You decide to use ketamine as your induction agent in this case and successfully intubate the critically ill patient.

Thank you to Dr. Amber Gombash, who is an emergency physician in Concord, N.C., for her help with this article.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

Dr. Milne is chief of emergency medicine and chief of staff at South Huron Hospital, Ontario, Canada. He is on the Best Evidence in Emergency Medicine faculty and is creator of the knowledge translation project the Skeptics’ Guide to Emergency Medicine.