Study Question: Do differences in ICU length of stay (LOS), time on mechanical ventilation, prevalence of delirium, and short-term mortality exist between benzodiazepine and nonbenzodiazepine sedation strategies?
Study Description: This systematic review and meta-analysis included trials from December 1996 through February 2013 that met the following criteria: 1) randomized controlled parallel group trial; 2) adult medical or surgical ICU patients receiving invasive mechanical ventilation and administration of IV sedation; 3) the use of IV dexmedetomidine or 1% propofol regardless of dose or duration compared to a control group receiving IV lorazepam or midazolam irrespective of dose, duration, or frequency; 4) outcomes such as ICU LOS, duration of mechanical ventilation, delirium prevalence, and all-cause, short-term mortality.
Results: Six trials enrolling 1,235 patients were included: midazolam vs. dexmedetomidine (n = 3), lorazepam vs. dexmedetomidne (n = 1), midazolam vs propofol (n = 1), and lorazepam versus propofol (n = 1). A nonbenzodiazepine sedation strategy was associated a shorter ICU LOS (trial n = 6; difference = 1.62 days; 95% CI, 0.68 – 2.55; I2 = 0%; p = 0.0007) and duration of mechanical ventilation (n = 4; difference = 1.9 days; 95% CI, 1.70 – 2.09; I2 = 0%; p < 0.00001). However, the nonbenzodiazepine sedation strategy was found to have a similar prevalence of delirium (n=2; risk ratio = 0.83; 95% CI, 0.61-1.11; I2 = 84%; p = 0.19) and short-term mortality rate (n=4; risk ratio = 0.98; 95% CI, 0.76-1.27; I2 = 30%; p = 0.88).
Conclusion(s): Current data suggests that use of nonbenzodiazepine-based sedation rather than benzodiazepine-based sedation in critically ill adults may result in decreased ICU LOS and duration of mechanical ventilation.
Perspective: Daily interruption of sedation, influence of industry, sedation protocolization, and ventilator weaning were all considered when evaluating bias of the studies. Two of the included studies were not in accordance with current standards of care (i.e., lorazepam infusions with bolusing and midazolam infusions without daily awakening). Heterogeneity was observed in the incidence of delirium and mortality, lowering the authors’ confidence in their ability to extrapolate the pooled results. The standard definition of delirium also varied among the studies. Far from providing the final word on nonbenzodiazepine-based sedation strategies and their effects on delirium and short-term mortality, the meta-analysis highlights the need for additional research in the area.