Associations Between Different Sedatives and Ventilator-Associated Events, Length of Stay, and Mortality in Patients Who Were Mechanically Ventilated

Abstract

Background: Current sedation guidelines recommend avoiding benzodiazepines but express no preference for propofol vs dexmedetomidine. In addition, few data exist on whether randomized controlled trials of sedatives can be successfully generalized to routine practice, in which conditions tend to be more varied and complex.

Methods: Data regarding daily sedative exposure were gathered from all patients undergoing mechanical ventilation for ≥ 3 days over a 7-year period in a large academic medical center. Hazard ratios (HRs) were compared for ventilator-associated events (VAEs), extubation, hospital discharge, and hospital death among patients receiving benzodiazepines, propofol, and dexmedetomidine. Proportional subdistribution hazard models with competing risks were used for analysis. All analyses were adjusted for ICU type, demographic characteristics, comorbidities, procedures, severity of illness, hypotension, oxygenation, renal function, opioids, neuroleptic agents, neuromuscular blockers, awakening and breathing trials, and calendar year.

Results: A total of 9,603 consecutive episodes of mechanical ventilation were evaluated. Benzodiazepines and propofol were associated with increased VAE risk, whereas dexmedetomidine was not. Propofol was associated with less time to extubation compared with benzodiazepines (HR, 1.4; 95% CI, 1.3-1.5). Dexmedetomidine was associated with less time to extubation compared with benzodiazepines (HR, 2.3; 95% CI, 2.0-2.7) and propofol (HR, 1.7; 95% CI, 1.4-2.0), but relatively few dexmedetomidine exposures were available for analysis. There were no differences between any two agents in HRs for hospital discharge or mortality.

Conclusions: In this large, real-world cohort, propofol and dexmedetomidine were associated with less time to extubation compared with benzodiazepines, but dexmedetomidine was also associated with less time to extubation vs propofol. These possible differences merit further study.

Keywords: mechanical ventilation; quality improvement; sedation.