Propofol versus ketamine in rapid sequence intubation in critically ill patients: a prospective, randomized, controlled trial.

Schmidt, Raysa Cristina; Godinho Zampieri, Fernando; da Silva Ramos, Fernando Jose; Santos Cavatoni Serra, Felipe; Maccagnan Pinheiro Besen, Bruno Adler; Fonseca Nunes, Nathaly; Boschetti, Daniela; Chohfi Atallah, Fernanda et al. · Intensive Care Med · 2026

rct · Level II

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Abstract

The optimal hypnotic agent for rapid sequence intubation (RSI) in critically ill patients remains uncertain. We evaluated whether Ketamine is a better alternative than propofol. In this investigator-initiated, randomized, controlled, open-label trial conducted in two mixed ICU, adults (≥ 18 years) requiring RSI were assigned 1:1 to Ketamine or propofol. The primary outcome was the lowest mean arterial pressure (MAP) within the first 10 min after induction, analyzed with a linear regression model adjusted for age, baseline MAP, and total vasopressor dose within 10 min. From October 2021 to October 2023, 207 patients were randomized and 175 were included in the modified intention-to-treat analysis. The lowest MAP within 10 min was 66 (55-79) mmHg with Ketamine and 60 (48-72) mmHg with propofol (mean difference, 6.0 [95% CI - 0.0 to 11.9]; p = 0.050). The average MAP difference over the first hour was 1.67 (95% CI - 1.98 to 5.31). Cardiovascular collapse occurred in 20/91(22%) Ketamine-treated patients and 28/84 (33%) receiving propofol, mainly due to an increase in the vasopressor dose within 2 min. Day-7 mortality was 33% with Ketamine and 23.8% with propofol (OR 1.38; 95% CI 0.86-2.24). Hospital mortality was 60.4% and 50.0%, respectively (OR 1.21; 95% CI 0.92-1.58). Among critically ill patients undergoing RSI, Ketamine resulted in a less pronounced decrease in MAP in the first 10 min compared with propofol, but the difference was not clinically meaningful or sustained. These findings challenge sedative selection based solely on perceived risk of hypotension and highlight the need for larger trials to determine the optimal induction agent. NCT05092152-initial release 10.13.2021.

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