Effect of Early Dexmedetomidine Addition on Prognosis in Mechanically Ventilated Patients Under Propofol Sedation: A Target Trial Emulation Study

Background: Combination propofol-dexmedetomidine (DEX) therapy may affect patient prognosis. However, it remains unknown whether the effects of this combination depend on the timing of DEX initiation. Objective: This study aimed to investigate the association between early initiation of DEX and mortality in mechanically ventilated patients receiving propofol sedation. Methods: This study was based on the Medical Information Mart for Intensive Care database. Two strategies were established via target trial emulation: strategy A, in which DEX was added within 24 hours of propofol initiation and maintained for ≥4 hours; strategy B, in which only propofol was used throughout the treatment period. The Clone-Censor-Weight (CCW) framework was applied to eliminate immortal time bias; multivariate Cox regression was performed to evaluate 28-day mortality. Weighted logistic regression was applied to evaluate safety outcomes such as 7-day acute kidney injury (AKI), bradycardia, and hypotension, followed by exploratory subgroup analyses. Results: Among 10 896 patients, fully adjusted CCW-Cox regression revealed that early initiation of DEX was associated with a lower risk of 28-day mortality (hazard ratio [HR] = 0.663, 95% confidence interval [CI], 0.551-0.798, P < .001). Fully adjusted logistic regression indicated that early initiation of DEX was not significantly associated with the odds of developing AKI within 7 days ( P = .163). Early DEX initiation was associated with higher odds of bradycardia (odds ratio [OR] = 1.70, 95% CI, 1.34-2.13, P < .001) and severe hypotension (OR = 1.23, 95% CI, 1.02-1.48, P = .031). The association with mild hypotension did not reach statistical significance (OR = 1.24, 95% CI, 0.98-1.60, P = .080). Conclusion and Relevance: In mechanically ventilated patients receiving propofol sedation, early initiation of DEX was associated with a reduced risk of 28-day mortality but increased odds of bradycardia and severe hypotension. These findings indicate that the potential benefits of early DEX use should be carefully weighed against its cardiovascular safety risks in clinical practice. Further prospective studies are warranted to validate the present results.