Induction Agents for Tracheal Intubation of Critically Ill Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
Chest · 2026-08-18 · Meta-analysis
Abstract
BACKGROUND: Tracheal intubation is a common yet high-risk procedure in critically ill patients, with as many as one-half experiencing peri-intubation adverse outcomes. RESEARCH QUESTION: What is the comparative effectiveness and safety of various sedative agents used for endotracheal intubation of critically ill patients in the emergency department (ED), ICU, operating room, and prehospital setting? STUDY DESIGN AND METHODS: We conducted a network meta-analysis and systematic review of randomized controlled trials. We searched MEDLINE, EMBASE, PubMed, Cochrane, and trial registries from inception through December 10, 2025, for randomized controlled trials (RCTs) comparing ≥ 2 sedative agents in critically ill adults or children undergoing endotracheal intubation. Outcomes of interest were hemodynamic instability during intubation, hypoxemia, cardiac arrest, mortality, ICU 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 approach to rate certainty in estimates. RESULTS: We included 21 RCTs enrolling 6,031 patients across ICU, ED, operating room, and prehospital settings. Compared with etomidate, more hemodynamic instability exists during intubation with ketamine (relative risk [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 postintubation continuous infusion vasopressors (RR, 0.80; 95% CI, 0.50-1.28; low certainty). Etomidate caused increased adrenal suppression compared with other agents. INTERPRETATION: Our results show that when considering sedation agents for endotracheal intubation of critically ill patients, etomidate probably causes less hemodynamic instability during intubation when compared with ketamine. However, etomidate may increase the need for the initiation of postintubation 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, although the available evidence is too limited and uncertain to support firm conclusions, and further randomized trials are needed. CLINICAL TRIAL REGISTRATION: International Prospective Register of Systematic Reviews; No.: CRD42024600739; URL: https://www.crd.york.ac.uk/prospero/.
Tags
Anaesthetics · Endotracheal intubation · Ketamine · Propofol · Rapid sequence intubation