Comparative Efficacy of Dexmedetomidine Versus Propofol for Sedation in Mechanically Ventilated Adult Patients with Sepsis: A systematic review and meta-analysis

Abstract

Current clinical guidelines recommend dexmedetomidine and propofol as first-line sedatives for mechanically ventilated patients. This systematic review and meta-analysis aimed to compare the efficacy and safety of dexmedetomidine versus propofol in mechanically ventilated adults with sepsis or septic shock. PubMed, Embase, CENTRAL, Scopus, Web of Science, and clinical registries were searched for randomized controlled trials (RCTs) and comparative observational studies published in English up to May 2026. The primary outcome was 28/30-day all-cause mortality. Secondary outcomes included duration of mechanical ventilation (MV), ICU length of stay (LOS), delirium incidence, and bradycardia. Random-effects meta-analyses utilized the Restricted Maximum Likelihood (REML) estimator with Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustments. Trial Sequential Analysis (TSA) was performed to assess information size and statistical power. Certainty of evidence was appraised using the GRADE framework. Ten studies (7 RCTs and 3 comparative observational cohorts) comprising 54,430 patients were included. Meta-analysis revealed no statistically significant difference in 28/30-day mortality between dexmedetomidine and propofol (RR, 0.90; 95% CI 0.68–1.21; p=0.435; I²=54.5%). TSA confirmed that the accrued sample size exceeded the Required Information Size (4,036 patients), validating the null finding. There were no significant differences in the duration of MV (MD, -1.13 days; 95% CI -3.46-1.20), ICU LOS (MD -1.54 days; 95% CI -3.59-0.52), or the incidence of delirium (RR 0.87; 95% CI 0.14–5.21). Dexmedetomidine was associated with a statistically non-significant trend toward an increased risk of bradycardia (RR 2.46; 95% CI 0.73–8.31). The overall certainty of evidence was rated as low to very low due to open-label designs, clinical inconsistency, and imprecision. In mechanically ventilated adults with sepsis, dexmedetomidine does not improve short-term mortality, mechanical ventilation duration, or ICU length of stay compared to propofol. The choice of sedative agent should be highly individualized based on patient-specific hemodynamic profiles and critical care goals rather than an expectation of a survival advantage.