Safety and efficacy of volatile sedatives in critically ill patients receiving mechanical ventilation: A systematic review and meta-analysis

Volatile sedatives are increasingly utilised for sedation in critically ill patients receiving invasive mechanical ventilation. Despite numerous randomised controlled trials and observational studies comparing volatile sedation to intravenous sedation, questions regarding its safety and efficacy persist. A systematic search was performed in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases for studies published up to July 2025. The analysis included randomised controlled trials and observational studies that compared the use of volatile sedation with intravenous sedation in patients admitted to the intensive care unit for mechanical ventilation. Eligible studies involved adults aged ⩾18 years, requiring mechanical ventilation, and utilising either volatile or intravenous sedatives. They also needed to report at least one outcome of interest: incidence of delirium, mortality, intensive care unit length of stay, or duration of mechanical ventilation. From 3182 identified publications, fifteen studies were included in the systematic review. Volatile sedation was not associated with a significant difference in the incidence of delirium compared to intravenous sedation (risk ratio 0.72; 95% confidence interval 0.38-1.34), mortality (risk ratio 0.97; 95% confidence interval 0.80-1.17), intensive care unit length of stay (mean difference 0.28 days; 95% confidence interval -1.74 to 2.30), or duration of mechanical ventilation (mean difference -37.20 h; 95% confidence interval -78.60 to 4.20). Volatile sedation was not associated with significant differences in mechanical ventilation duration, delirium incidence, intensive care unit length of stay, or mortality compared to intravenous sedation. Further large-scale, high-quality randomised trials are needed to clarify its clinical benefit in critical care settings.