title: A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients.
abstract: OBJECTIVE
  To determine if midazolam is superior to lorazepam or haloperidol in the management of violent and severely agitated patients in the emergency department. Superiority would be determined if midazolam resulted in a significantly shorter time to sedation and shorter time to arousal.
  
  
  METHODS
  This was a randomized, prospective, double-blind study of a convenience sample of patients from an urban, county teaching emergency department. Participants included 111 violent and severely agitated patients. Patients were randomized to receive intramuscular midazolam (5 mg), lorazepam (2 mg), or haloperidol (5 mg).
  
  
  RESULTS
  The mean (+/-SD) age was 40.7 (+/-13) years. The mean (+/-SD) time to sedation was 18.3 (+/-14) minutes for patients receiving midazolam, 28.3 (+/-25) minutes for haloperidol, and 32.2 (+/-20) minutes for lorazepam. Midazolam had a significantly shorter time to sedation than lorazepam and haloperidol (p < 0.05). The mean difference between midazolam and lorazepam was 13.0 minutes (95% confidence interval [95% CI] = 5.1 to 22.8 minutes) and that between midazolam and haloperidol was 9.9 minutes (95% CI = 0.5 to 19.3 minutes). Time to arousal was 81.9 minutes for patients receiving midazolam, 126.5 minutes for haloperidol, and 217.2 minutes for lorazepam. Time to arousal for midazolam was significantly shorter than for both haloperidol and lorazepam (p < 0.05). The mean difference in time to awakening between midazolam and lorazepam was 135.3 minutes (95% CI = 89 to 182 minutes) and that between midazolam and haloperidol was 44.6 minutes (95% CI = 9 to 80 minutes). There was no significant difference over time by repeated-measures analysis of variance between groups in regard to changes in systolic and diastolic blood pressure (p = 0.8965, p = 0.9581), heart rate (p = 0.5517), respiratory rate (p = 0.8191), and oxygen saturation (p = 0.8991).
  
  
  CONCLUSIONS
  Midazolam has a significantly shorter time to onset of sedation and a more rapid time to arousal than lorazepam or haloperidol. The efficacies of all three drugs appear to be similar.
authors.affiliation: Division of Emergency Medicine, Department of Internal Medicine, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Flavia
authors.initials: F
authors.lastname: Nobay
authors.forename: Barry C
authors.initials: BC
authors.lastname: Simon
authors.forename: M Andrew
authors.initials: MA
authors.lastname: Levitt
authors.forename: Graham M
authors.initials: GM
authors.lastname: Dresden
mesh_terms: D000328:Adult; D001143:Arousal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D006220:Haloperidol / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008140:Lorazepam / Q000627:therapeutic use; D008874:Midazolam / Q000627:therapeutic use*; D011446:Prospective Studies; D011595:Psychomotor Agitation / Q000188:drug therapy*; D015656:Respiratory Mechanics / Q000187:drug effects; D014149:Tranquilizing Agents / Q000627:therapeutic use*; D016896:Treatment Outcome; D014754:Violence / Q000517:prevention & control*
chemical_list: D014149:Tranquilizing Agents; D006220:Haloperidol; D008140:Lorazepam; D008874:Midazolam