Induction Agents for Tracheal Intubation of Critically Ill Patients: A Systematic Review and Network Meta-Analysis of...

Tracheal intubation is a common yet high risk procedure in the critically ill with as many as half experiencing peri-intubation adverse outcomes.

We aimed to evaluate the comparative effectiveness and safety of various sedative agents used for endotracheal intubation of the critically ill patient in the emergency department, intensive care unit, operating room, and pre-hospital setting.

We conducted a network meta-analysis and systematic review of randomized controlled trials. We searched MEDLINE, EMBASE, PubMed, Cochrane, and trial registries from inception to December 10, 2025 for Randomized controlled trials (RCTs) comparing two or more sedative agents in critically ill adults or children undergoing endotracheal intubation. Outcomes of interest were hemodynamic instability during intubation, hypoxemia, cardiac arrest, mortality, intensive care unit and hospital length of stay, vasopressor use, adrenal insufficiency, and first-pass success. Reviewers screened, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool independently and in duplicate. We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates.

We included 21 RCTs enrolling 6,031 patients across Intensive Care Unit, Emergency Department, Operating Room, and pre-hospital settings. Compared with etomidate, there is probably more hemodynamic instability during intubation with ketamine (RR 1.31, 95% CI 1.15-1.48; moderate certainty). Ketamine-propofol may decrease hemodynamic instability during intubation compared with etomidate (RR 0.44, 95% CI 0.27-0.72; low certainty) and ketamine (RR 0.34, 95% CI 0.21-0.56; low certainty). Compared with etomidate, ketamine may decrease the need for the initiation of post-intubation continuous infusion vasopressors (RR 0.80, 95% CI 0.50-1.28; low certainty). Etomidate caused increased adrenal suppression compared with other agents.

When considering sedation agents for endotracheal intubation of the critically ill, etomidate probably causes less hemodynamic instability during intubation when compared with ketamine. However, etomidate may increase the need for the initiation of post-intubation continuous infusion vasopressors when compared with ketamine and increases adrenal suppression. The clinical importance of these competing effects remains uncertain. Ketamine-propofol may decrease hemodynamic instability during intubation when compared with etomidate and ketamine though the available evidence is too limited and uncertain to support firm conclusions and further randomized trials are needed.