Ketamine Versus Etomidate for Tracheal Intubation in Critically Ill Adults

Key Takeaways

• Ketamine was not associated with a significant reduction in day-28 in-hospital death versus etomidate.
• Cardiovascular collapse was reported more often with ketamine during intubation.
• Prespecified safety outcomes were similar in critically ill adults treated in US emergency departments and ICUs.

A randomized NEJM trial compared ketamine with etomidate for induction during tracheal intubation in 2365 critically ill adults treated in US emergency and intensive care settings. Day-28 in-hospital death was similar between groups, while cardiovascular collapse during intubation occurred more often with ketamine. Both treatments were evaluated within the same randomized trial, keeping the comparison focused on the assigned agents.

The trial was conducted in 14 emergency departments and intensive care units in the United States and enrolled critically ill adults undergoing tracheal intubation. Overall, 2365 patients underwent randomization, with 1176 assigned to ketamine and 1189 assigned to etomidate. The primary outcome was in-hospital death from any cause by day 28. The secondary outcome was cardiovascular collapse during intubation, defined by systolic blood pressure below 65 mm Hg, a new or increased vasopressor dose, or cardiac arrest.

By day 28, in-hospital death occurred in 330 of 1173 patients in the ketamine group and 345 of 1186 patients in the etomidate group. Those event rates were 28.1% with ketamine and 29.1% with etomidate. The adjusted risk difference for death was -0.8 percentage points, with a 95% confidence interval from -4.5 to 2.9. The reported P value was 0.65, which did not indicate a significant reduction in day-28 mortality with ketamine versus etomidate.

For cardiovascular collapse during intubation, events occurred in 260 of 1176 patients assigned to ketamine and 202 of 1189 assigned to etomidate. Those rates were 22.1% and 17.0%, respectively, yielding a risk difference of 5.1 percentage points between the two groups. The 95% confidence interval for that difference ranged from 1.9 to 8.3 percentage points. Prespecified safety outcomes were similar in the two groups.