title: Midazolam-Droperidol, Droperidol, or Olanzapine for Acute Agitation: A Randomized Clinical Trial.
abstract: OBJECTIVE
  We aim to determine the most efficacious of 3 common medication regimens for the sedation of acutely agitated emergency department (ED) patients.
  
  
  METHODS
  We undertook a randomized, controlled, double-blind, triple-dummy, clinical trial in 2 metropolitan EDs between October 2014 and August 2015. Patients aged 18 to 65 years and requiring intravenous medication sedation for acute agitation were enrolled and randomized to an intravenous bolus of midazolam 5 mg-droperidol 5 mg, droperidol 10 mg, or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg, or olanzapine 5 mg. The primary outcome was the proportion of patients adequately sedated at 10 minutes.
  
  
  RESULTS
  Three hundred forty-nine patients were randomized to the 3 groups. Baseline characteristics were similar across the groups. Ten minutes after the first dose, significantly more patients in the midazolam-droperidol group were adequately sedated compared with the droperidol and olanzapine groups: differences in proportions 25.0% (95% confidence interval [CI] 12.0% to 38.1%) and 25.4% (95% CI 12.7% to 38.3%), respectively. For times to sedation, the differences in medians between the midazolam-droperidol group and the droperidol and olanzapine groups were 6 (95% CI 3 to 8) and 6 (95% CI 3 to 7) minutes, respectively. Patients in the midazolam-droperidol group required fewer additional doses or alternative drugs to achieve adequate sedation. The 3 groups' adverse event rates and lengths of stay did not differ.
  
  
  CONCLUSIONS
  Midazolam-droperidol combination therapy is superior, in the doses studied, to either droperidol or olanzapine monotherapy for intravenous sedation of the acutely agitated ED patient.
authors.affiliation: Emergency Department, Austin Health, Heidelberg, Victoria, Australia. Electronic address: david.taylor@austin.org.au.
authors.forename: David McD
authors.initials: DM
authors.lastname: Taylor
authors.affiliation: Centre for Medicine Use and Safety, Monash University, Parkville, Victoria, Australia.
authors.forename: Celene Y L
authors.initials: CYL
authors.lastname: Yap
authors.affiliation: Emergency Department, Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Knott
authors.affiliation: Pharmacy Department, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Simone E
authors.initials: SE
authors.lastname: Taylor
authors.affiliation: Emergency Department, St Vincent's Hospital, Victoria Parade, Victoria, Australia.
authors.forename: Georgina A
authors.initials: GA
authors.lastname: Phillips
authors.affiliation: Emergency Department, St Vincent's Hospital, Victoria Parade, Victoria, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Karro
authors.affiliation: Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Chan
authors.affiliation: Centre for Medicine Use and Safety, Monash University, Parkville, Victoria, Australia.
authors.forename: David C M
authors.initials: DCM
authors.lastname: Kong
authors.affiliation: St Vincent's Hospital and the University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Castle
mesh_terms: D000208:Acute Disease; D000328:Adult; D001569:Benzodiazepines / Q000627:therapeutic use*; D016292:Procedural Sedation / Q000379:methods*; D004311:Double-Blind Method; D004329:Droperidol / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004636:Emergency Service, Hospital; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000627:therapeutic use*; D000077152:Olanzapine; D011595:Psychomotor Agitation / Q000188:drug therapy*
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D000077152:Olanzapine; D004329:Droperidol; D008874:Midazolam