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

Abstract

Objective: Specific 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 sources: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, Scopus and Web of science databases. Study selection: We 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 extraction: Two 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 synthesis: Acute 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. Conclusions: Acute 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.