There remains significant controversy regarding the optimal induction agent for rapid sequence intubation (RSI), particularly when comparing etomidate and ketamine. Concerns surrounding etomidate center on its potential to cause transient adrenal suppression, which has raised questions about possible harm in critically ill patients. However, it is unclear whether this theoretical risk translates into meaningful clinical outcomes, especially given that these patients often present with existing or impending multi-organ dysfunction. In this context, attributing adverse outcomes to a single induction dose, without robust control or randomization, may overstate its clinical impact.
Despite these ongoing debates, recent evidence has helped clarify this issue. By the end of 2025, two notable studies were published comparing etomidate and ketamine for RSI in critically ill patients.
NEJM, Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults
“The use of ketamine to induce anesthesia did not result in a significantly lower incidence of in-hospital death by day 28 than etomidate.”
JAMA, Ketamine, Etomidate, and Mortality in Emergency Department Intubations
“In this cohort study of critically ill adults undergoing RSI, etomidate use was associated with higher in-hospital mortality at 7 and 28 days compared with ketamine.”