Ketamine vs Etomidate for Emergency Intubation (The RSI Trial): No Mortality Difference, But Important Hemodynamic Considerations
- Mazen Kherallah
- 5 days ago
- 3 min read
Induction agents for emergency tracheal intubation are foundational in critical care practice, where even brief perturbations in hemodynamics can have lasting consequences and mortality risk is substantial. Etomidate, long favored for its rapid onset and relative cardiovascular neutrality, has been increasingly scrutinized because of its well-described suppression of adrenal steroidogenesis and concerns—largely observational—that this effect may translate into worse outcomes in critically ill and septic patients.
Ketamine, a dissociative anesthetic with sympathomimetic properties, has emerged as a commonly used alternative and is often preferentially selected in patients with shock or limited physiologic reserve. However, ketamine is also a direct myocardial depressant and vasodilator, and growing evidence has linked its use during intubation to hypotension and cardiovascular complications in vulnerable populations.
Against this backdrop of competing physiologic theories and conflicting clinical data, the Randomized Trial of Sedative Choice for Intubation (RSI)—a large, pragmatic randomized controlled trial—directly compared ketamine and etomidate in real-world ICU and emergency department settings to clarify their effects on survival and periprocedural hemodynamic stability.
Which sedative agent do you prefer for intubation?
0%Ketamine
0%Etomidate
0%It depends
0%I do not know
RSI Trial
The study enrolled critically ill adults (≥18 years) undergoing emergency tracheal intubation in 14 ICUs and EDs across six U.S. centers. Patients were eligible if they required an induction agent for intubation and were excluded if they had trauma, pregnancy, incarceration, or urgent airway needs that precluded randomization. Notably, 46.7% had sepsis or septic shock, and 22% were receiving vasopressors—reflecting a high-acuity, real-world population.
Patients in the intervention group received intravenous ketamine for induction, with dosing (1.0–2.0 mg/kg) selected by the clinician based on a weight-based nomogram. Administration fidelity was high (99.2%), and other aspects of care—such as paralytics and post-intubation sedation—were at clinician discretion.
The comparator group received intravenous etomidate (0.2–0.3 mg/kg), also guided by a weight-based nomogram. Etomidate was administered as intended in 99.6% of patients. Both groups had similar use of neuromuscular blockade and airway techniques, supporting protocol consistency across sites.
The primary outcome was in-hospital mortality by day 28. Secondary outcomes included cardiovascular collapse during intubation (SBP <65 mm Hg, new or increased vasopressors, or cardiac arrest). Among 2,365 patients randomized, mortality was similar: 28.1% with ketamine vs. 29.1% with etomidate (adjusted risk difference -0.8%; 95% CI -4.5 to 2.9; P=0.65). However, cardiovascular collapse was more frequent with ketamine (22.1% vs. 17.0%), particularly in patients with sepsis or high APACHE II scores.
Insights and Takeaways
The RSI trial provides important clarity for induction agent selection during emergency tracheal intubation. With no difference in mortality between ketamine and etomidate, clinicians can make induction choices based on patient-specific physiology and clinical context rather than concerns about survival. This finding supports flexibility in drug selection, allowing for individualized approaches in critically ill patients.
However, ketamine was associated with a higher incidence of cardiovascular collapse, particularly among patients with sepsis or high illness severity. This underscores the importance of hemodynamic risk stratification when selecting an induction agent. In patients with limited cardiovascular reserve, ketamine may increase the risk of hypotension, vasopressor escalation, or arrest during the periprocedural period.
Though ketamine is often favored for its potential to support blood pressure via endogenous catecholamine release, its negative inotropic and vasodilatory effects may dominate in critically ill patients—especially those with shock or catecholamine depletion. The assumption that ketamine is always hemodynamically safer than etomidate is not supported by these findings. Induction agents should be selected not by protocol alone, but by careful evaluation of each patient’s physiology and clinical trajectory.
Conclusion
The RSI trial delivers high-quality evidence to guide induction agent selection in critically ill adults undergoing emergency intubation. While ketamine and etomidate demonstrate equivalent outcomes with respect to short-term mortality, their hemodynamic profiles differ meaningfully. Etomidate was associated with greater cardiovascular stability, particularly in high-risk subgroups such as those with sepsis or elevated illness severity. For ICU clinicians, this reinforces the need to tailor induction choices to individual patient physiology, moving beyond assumptions of drug safety based solely on pharmacologic theory.