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Original paper
2026NEJMEmergency Medicine

RSI

Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults

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Overview

For emergency intubation, ketamine did not lower 28-day in-hospital death compared with etomidate.

Clinical takeaway

RSI showed that choosing ketamine instead of etomidate does not improve 28-day in-hospital survival, and cardiovascular collapse during intubation was more common with ketamine.

Key result

In-hospital death by day 28 was 28.1% with ketamine vs 29.1% with etomidate (site-adjusted risk difference -0.8 percentage points; 95% CI -4.5 to 2.9; p=0.65).

Practice impact

Either ketamine or etomidate is acceptable for induction; ketamine does not improve survival, and cardiovascular collapse was more common with ketamine.

Evidence

Study design

Randomized trial in 14 emergency departments and intensive care units in the United States.

Enrollment

2,365

Follow-up

In-hospital death from any cause by day 28.

Geography

United States

Clinical question

Does ketamine rather than etomidate for induction reduce 28-day in-hospital death in critically ill adults undergoing tracheal intubation?

Population

  • Critically ill adults undergoing tracheal intubation in an emergency department or ICU.

Intervention

Ketamine for induction of anesthesia.

Comparator

Etomidate for induction of anesthesia.

Primary outcome

In-hospital death from any cause by day 28.

Ketamine did not significantly reduce 28-day in-hospital death compared with etomidate.

Risk difference (site-adjusted) / -0.8 / 95% CI -4.5 to 2.9 / p=0.65

Key results

  • In-hospital death by day 28: 28.1% with ketamine vs 29.1% with etomidate; site-adjusted risk difference -0.8 percentage points (95% CI -4.5 to 2.9; p=0.65).
  • Cardiovascular collapse during intubation was more common with ketamine (22.1% vs 17.0%; risk difference 5.1 percentage points; 95% CI 1.9-8.3).
  • Prespecified safety outcomes were similar in the two groups.

Harms

  • Cardiovascular collapse during intubation occurred in 22.1% with ketamine and 17.0% with etomidate.
  • Prespecified safety outcomes were similar in the two groups.

Clinical Use

Practice impact

  • Either ketamine or etomidate is acceptable for induction; ketamine does not improve survival, and cardiovascular collapse was more common with ketamine.

Applicability

  • Most applicable to critically ill adults undergoing emergency tracheal intubation in a U.S. emergency department or ICU.

Limitations

  • The trial compared two induction drugs and does not address neuromuscular blockade, preoxygenation, or laryngoscope choice.
  • Cardiovascular collapse was a secondary outcome that favored etomidate, but the abstract does not report component events separately.
  • Observational concern that etomidate increases death was not confirmed here.

Common misinterpretations

  • RSI does not show etomidate is safer overall; 28-day death was similar and prespecified safety outcomes did not differ.
  • More peri-intubation cardiovascular collapse with ketamine is not the same as higher later mortality.

Related evidence

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Citation

Casey JD, Seitz KP, Driver BE, et al. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults. N Engl J Med. 2026;394(16):1608-1620. doi:10.1056/NEJMoa2511420

Among critically ill adults undergoing tracheal intubation, the use of ketamine to induce anesthesia did not result in a significantly lower incidence of in-hospital death by day 28 than etomidate.