Real-World Evidence for Combination Sedation: Propofol Plus Dexmedetomidine and Clinical Outcomes in Mechanically Ventilated ICU Patients

Purpose: This retrospective multicenter cohort study evaluated the real-world effectiveness of propofol alone versus a propofol-plus-dexmedetomidine combination on clinical outcomes in mechanically ventilated ICU patients. Methods: Adult mechanically ventilated ICU patients receiving long-term continuous infusion sedation (≥ 48 h) with either propofol alone or propofol plus dexmedetomidine were identified from the MIMIC-IV and eICU databases. An external validation cohort from Nanjing Drum Tower Hospital (2013– 2022) was assembled using the same eligibility criteria. Patients were categorized into a propofol monotherapy group (Pro) and a propofol plus dexmedetomidine group (Pro+Dex). Outcomes included 28–day all-cause mortality, incident delirium, ICU length of stay, duration of mechanical ventilation, and longitudinal changes in mean arterial pressure, heart rate, and oxygen saturation. Results: Among 5495 patients (Pro: n=4730; Pro+Dex: n=765), the Pro+Dex regimen was associated with lower 28-day mortality (adjusted HR: 0.45, 95% CI: 0.36– 0.56; P < 0.001) and a markedly reduced incidence of delirium (adjusted OR: 0.28, 95% CI: 0.21– 0.37; P < 0.001), but with a modestly longer ICU stay (13.07 vs 10.60 days; adjusted ratio: 1.23, 95% CI: 1.18– 1.29). Mechanical ventilation duration did not differ significantly between groups (154.79 vs 157.64 hours; adjusted ratio: 0.98, 95% CI: 0.92– 1.05). Longitudinal mixed-effects models suggested a more stable MAP trajectory and lower HR with Pro+Dex, while SpO 2 was slightly lower on average but remained stable over time. Subgroup analyses were broadly consistent with the overall cohort. In the external validation cohort, Pro+Dex was also associated with significantly lower 28-day mortality, whereas the reduction in delirium incidence did not reach statistical significance. Conclusion: In this large real-world multicenter study, combination sedation with propofol and dexmedetomidine was associated with lower 28-day mortality and a lower risk of delirium, without a significant difference in mechanical ventilation duration, although ICU length of stay was modestly longer.