Sedative drugs used for mechanically ventilated patients in intensive care units: a systematic review and network meta-analysis

Background: The effects of different sedative drugs on all-cause mortality rate, duration of ICU stay, and risk of delirium in mechanically ventilated ICU patients are unclear. This meta-analysis aimed to compare the effectiveness and safety of individual sedative drugs and drug combinations in mechanically ventilated ICU patients. Materials and methods: Medline, Embase, Cochrane, EBSCOhost, and ISI Web of Science databases were searched for studies that assessed sedation in ICU mechanically ventilated patients. A Bayesian random-effects model was used to combine the direct comparisons and indirect evidence. Results: Thirty-one randomized, controlled trials were included, which consisted of 4491 patients who received one of seven sedative drugs or a combination of drugs. There were no significant differences regarding the all-cause mortality rate. Compared to propofol, inhalation anesthetics (hazard ratio [HR] 0.121; 95% credible interval [CrI] -7.58 to 7.62), alpha agonists (HR 2.2; 95% CrI 0.776 to 5.22), propofol with benzodiazepines (HR 0.306; 95% CrI -6.97 to 7.65), ketamine with benzodiazepines (HR 6.57; 95% CrI -6.05 to 19.1) and placebo (HR 2.4; 95% CrI -5.37 to 10.3), benzodiazepines (HR 3.62; 95% CrI 0.834 to 6.2) may increase the duration of ICU stay. Compared to alpha agonists, propofol (HR 2.4; 95% CrI 0.304 to 21.1) and placebo (HR 6.12; 95% CrI 0.745 to 54.6), benzodiazepines (HR 2.59; 95% CrI 1.08 to 7.4) were associated with incremental risks of delirium. Conclusion: Compared to propofol, benzodiazepines may increase the duration of ICU stay. Compared to alpha agonists, benzodiazepines were associated with an increased risk of delirium.