title: Benzodiazepine versus nonbenzodiazepine-based sedation for mechanically ventilated, critically ill adults: a systematic review and meta-analysis of randomized trials.
abstract: BACKGROUND
  Use of dexmedetomidine or propofol rather than a benzodiazepine sedation strategy may improve ICU outcomes. We reviewed randomized trials comparing a benzodiazepine and nonbenzodiazepine regimen in mechanically ventilated adult ICU patients to determine if differences exist between these sedation strategies with respect to ICU length of stay, time on the ventilator, delirium prevalence, and short-term mortality.
  
  
  METHODS
  We searched CINAHL, MEDLINE, the Cochrane databases, and the American College of Critical Care Medicine's Pain, Agitation, Delirium Management Guidelines' literature database from 1996 to 2013. Citations were screened for randomized trials that enrolled critically ill, mechanically ventilated adults comparing an IV benzodiazepine-based to a nonbenzodiazepine-based sedative regimen and reported duration of ICU length of stay, duration of mechanical ventilation, delirium prevalence, and/or short-term mortality. Trial characteristics and results were abstracted in duplicate and independently, and the Cochrane risk of bias tool was used for quality assessment. We performed random effects model meta-analyses where possible.
  
  
  RESULTS
  We included six trials enrolling 1,235 patients: midazolam versus dexmedetomidine (n = 3), lorazepam versus dexmedetomidine (n = 1), midazolam versus propofol (n = 1), and lorazepam versus propofol (n = 1). Compared to a benzodiazepine sedative strategy, a nonbenzodiazepine sedative strategy was associated with a shorter ICU length of stay (n = 6 studies; difference = 1.62 d; 95% CI, 0.68-2.55; I = 0%; p = 0.0007) and duration of mechanical ventilation (n = 4 studies; difference = 1.9 d; 95% CI, 1.70-2.09; I2 = 0%; p < 0.00001) but 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).
  
  
  CONCLUSIONS
  Current controlled data suggest that use of a dexmedetomidine- or propofol-based sedation regimen rather than a benzodiazepine-based sedation regimen in critically ill adults may reduce ICU length of stay and duration of mechanical ventilation. Larger controlled studies are needed to further define the impact of nonbenzodiazepine sedative regimens on delirium and short-term mortality.
authors.affiliation: Department of Pharmacy, Tufts University School of Medicine, Boston, MA, USA. fraseg@mmc.org
authors.forename: Gilles L
authors.initials: GL
authors.lastname: Fraser
authors.forename: John W
authors.initials: JW
authors.lastname: Devlin
authors.forename: Craig P
authors.initials: CP
authors.lastname: Worby
authors.forename: Waleed
authors.initials: W
authors.lastname: Alhazzani
authors.forename: Juliana
authors.initials: J
authors.lastname: Barr
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Dasta
authors.forename: John P
authors.initials: JP
authors.lastname: Kress
authors.forename: Judy E
authors.initials: JE
authors.lastname: Davidson
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Spencer
mesh_terms: D000328:Adult; D001569:Benzodiazepines / Q000627:therapeutic use*; D016638:Critical Illness; D003693:Delirium / Q000517:prevention & control; D017052:Hospital Mortality; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007362:Intensive Care Units; D007902:Length of Stay; D016032:Randomized Controlled Trials as Topic; D012121:Respiration, Artificial
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines