Remimazolam versus conventional sedatives for sedation in mechanically ventilated critically ill adults: a systematic review and meta-analysis of 12 randomized trials with trial sequential analysis

This project hosts the study protocol and associated materials for a systematic review and meta-analysis comparing remimazolam with conventional sedatives (propofol, midazolam, and dexmedetomidine) for continuous intravenous sedation in mechanically ventilated critically ill adults. Purpose: Remimazolam is an ultra-short-acting benzodiazepine with organ-independent metabolism that is increasingly used for ICU sedation, but its efficacy and safety relative to standard-of-care sedatives have not been comprehensively quantified. This review synthesizes randomized controlled trials (with prospective cohort studies as a supplementary evidence layer) to compare hypotension incidence (primary safety outcome) and time within the target sedation range (primary efficacy outcome), as well as delirium, respiratory depression, bradycardia, rescue sedation, vasopressor requirement, duration of mechanical ventilation, time to extubation and awakening, ICU length of stay, and mortality. Methods: PubMed/MEDLINE and ClinicalTrials.gov were searched from inception to 6 September 2026. Risk of bias is assessed with the Cochrane RoB 2 tool (ROBINS-I for cohorts), certainty of evidence with GRADE, and trial sequential analysis is used to assess the accrued information size. Random-effects models (DerSimonian–Laird with Hartung–Knapp adjustment) are pooled separately by comparator class. Expected outcomes: An updated, comprehensive quantitative synthesis of remimazolam versus all three conventional comparators in ICU sedation, identifying where evidence is conclusive and where further large international trials are needed. Registration note: The protocol was finalized on 6 September 2026, before study selection began. Registration is retrospective relative to review completion and is provided for transparency and priority documentation.