Outcomes of Sedative Hypnotic Agents Used for Endotracheal Intubation in Critically Ill Adults: A Systematic Review with Exploratory Meta-Analysis

Abstract

ObjectiveSpecific sedative hypnotic agents, administered to facilitate endotracheal intubation (ETI) in critically ill adults, may lead to adverse outcomes such as peri-intubation cardiovascular collapse. However, little is known from systematic investigations of the impact these individual agents have on cardiovascular function or other clinical outcomes.Data sourcesMEDLINE, Embase, CENTRAL, ClinicalTrials.gov, Scopus and Web of science databases.Study selectionWe conducted a systematic search for randomized and non-randomized studies that evaluated adult (≥18 years) critically ill patients who were sedated to facilitate ETI with ketamine, propofol, ketamine/propofol, etomidate, or a benzodiazepine and who had data on peri-intubation hemodynamics and at least one other outcome involving acute kidney injury, delirium, opioid use, intubation difficulty, sequential organ failure assessment, length of stay, or mortality. Eighty-five studies were identified for eligibility assessment with 23 included in the analysis.Data extractionTwo reviewers independently screened articles, extracted data from selected articles, and assessed risk of bias using ROBINS-I for observational studies and revised Cochrane Risk of Bias tool for randomized controlled trials.Data synthesisAcute cardiovascular dysfunction (peri-intubation hemodynamic instability and/or cardiac arrest) was similar between etomidate and ketamine with more events seen when propofol versus non-propofol sedation was administered. However, exploratory meta-analysis demonstrated no difference between etomidate and ketamine (OR 1.05 [95%CI 0.60-1.84]) or between etomidate and propofol (OR 0.91 [95%CI 0.33-2.46]). Compared to ketamine, etomidate demonstrated lower survival to hospital discharge in the included studies in exploratory meta-analysis OR 0.76 (95%CI 0.62-0.92). Limited data existed for other outcomes with no discernible differences between sedative agents.ConclusionsAcute cardiovascular dysfunction was more common when propofol, as compared to non-propofol sedation, was administered, although not statistically significant in exploratory meta-analysis. In addition, etomidate conferred lower survival to hospital discharge versus non-etomidate sedation, which was confirmed in exploratory meta-analysis of etomidate versus ketamine.

Keywords: critically ill; endotracheal intubation; outcomes; sedation; systematic review.