REBEL Cast: The RSI Trial — Ketamine vs Etomidate in Critically Ill Adults

In this episode, we break down the 2025 NEJM RSI trial comparing ketamine and etomidate for tracheal intubation in critically ill adults (Casey et al., PMID: 41369227).

This multicenter randomized trial enrolled 2,365 patients across ED and ICU settings and asked a clinically important question: does ketamine improve 28-day mortality compared with etomidate?

What we cover:

• Primary outcome: no statistically significant difference in 28-day mortality

• Secondary signal: higher "cardiovascular collapse" with ketamine, largely driven by new/increased vasopressor use, not clear increases in arrest or profound hypotension

• Trial strengths: strong randomization, high protocol adherence, excellent follow-up

• Trial limitations: no blinding, equipoise-only enrollment, trauma exclusion, ketamine dose strategy (actual body weight; commonly higher than many bedside practices)

Clinical Bottom Line:

This trial does not support abandoning ketamine for RSI.

Etomidate remains a strong first-line option, particularly in patients at high risk of peri-intubation hemodynamic decompensation.

At the same time, a small potentially meaningful mortality difference in favor of ketamine remains possible and would require a larger study to confirm.

Read the full post on REBEL EM:

"The RSI Trial: Ketamine vs Etomidate in Rapid Sequence Intubation"