Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine among Critically Ill Patients

<b>Rationale:</b> Uncertainty remains regarding the risks associated with single-dose use of etomidate. <b>Objectives:</b> To assess the use of etomidate in critically ill patients and compare outcomes for patients who received etomidate versus ketamine. <b>Methods:</b> We assessed patients who received invasive mechanical ventilation (IMV) and were admitted to an ICU in the Premier Healthcare Database between 2008 and 2021. The exposure was receipt of etomidate on the day of IMV initiation, and the main outcome was hospital mortality. Using multivariable regression, we compared patients who received IMV within the first 2 days of hospitalization who received etomidate with propensity score-matched patients who received ketamine. We also assessed whether receipt of corticosteroids in the days after intubation modified the association between etomidate and mortality. <b>Measurements and Main Results:</b> Of 1,689,945 patients who received IMV, nearly half (738,855; 43.7%) received etomidate. Among those who received IMV in the first 2 days of hospitalization, we established 22,273 matched pairs administered either etomidate or ketamine. In the primary analysis, receipt of etomidate was associated with greater hospital mortality relative to ketamine (21.6% vs. 18.7%; absolute risk difference, 2.8%; 95% confidence interval, 2.1%, 3.6%; adjusted odds ratio, 1.28, 95% confidence interval, 1.21,1.34). This was consistent across subgroups and sensitivity analyses. We found no attenuation of the association with mortality with receipt of corticosteroids in the days after etomidate use. <b>Conclusions:</b> Use of etomidate on the day of IMV initiation is common and associated with a higher odds of hospital mortality than use of ketamine. This finding is independent of subsequent treatment with corticosteroids.