Associations Between Different Sedatives and Ventilator-Associated Events, Length of Stay, and Mortality in Patients Who Were Mechanically Ventilated.
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.
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA; Department of Medicine, Brigham and Women's Hospital, Boston, MA. Electronic address: mklompas@partners.org.
Michael
M
Klompas
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA.
Lingling
L
Li
Department of Pharmacy, Brigham and Women's Hospital, Boston, MA.
Paul
P
Szumita
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA.
Ken
K
Kleinman
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA.
Michael V
MV
Murphy
D000328:Adult; D000368:Aged; D060666:Airway Extubation / Q000379:methods*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects; D057186:Comparative Effectiveness Research; D016292:Procedural Sedation / Q000379:methods*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care; D015742:Propofol / Q000008:administration & dosage / Q000009:adverse effects; D012121:Respiration, Artificial / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D012189:Retrospective Studies; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D012122:Ventilators, Mechanical / Q000706:statistics & numerical data
D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D020927:Dexmedetomidine; D015742:Propofol
mechanical ventilation; quality improvement; sedation