title: Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: a randomised open-label trial.
abstract: BACKGROUND
  Agitated delirium is common in patients undergoing mechanical ventilation, and is often treated with haloperidol despite concerns about safety and efficacy. Use of conventional sedatives to control agitation can preclude extubation. Dexmedetomidine, a novel sedative and anxiolytic agent, may have particular utility in these patients. We sought to compare the efficacy of haloperidol and dexmedetomidine in facilitating extubation.
  
  
  METHODS
  We conducted a randomised, open-label, parallel-groups pilot trial in the medical and surgical intensive care unit of a university hospital. Twenty patients undergoing mechanical ventilation in whom extubation was not possible solely because of agitated delirium were randomised to receive an infusion of either haloperidol 0.5 to 2 mg/hour or dexmedetomidine 0.2 to 0.7 microg/kg/hr, with or without loading doses of 2.5 mg haloperidol or 1 mug/kg dexmedetomidine, according to clinician preference.
  
  
  RESULTS
  Dexmedetomidine significantly shortened median time to extubation from 42.5 (IQR 23.2 to 117.8) to 19.9 (IQR 7.3 to 24) hours (P = 0.016). Dexmedetomidine significantly decreased ICU length of stay, from 6.5 (IQR 4 to 9) to 1.5 (IQR 1 to 3) days (P = 0.004) after study drug commencement. Of patients who required ongoing propofol sedation, the proportion of time propofol was required was halved in those who received dexmedetomidine (79.5% (95% CI 61.8 to 97.2%) vs. 41.2% (95% CI 0 to 88.1%) of the time intubated; P = 0.05). No patients were reintubated; three receiving haloperidol could not be successfully extubated and underwent tracheostomy. One patient prematurely discontinued haloperidol due to QTc interval prolongation.
  
  
  CONCLUSIONS
  In this preliminary pilot study, we found dexmedetomidine a promising agent for the treatment of ICU-associated delirious agitation, and we suggest this warrants further testing in a definitive double-blind multi-centre trial.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00505804.
authors.affiliation: Department of Intensive Care Medicine, Austin Hospital and the University of Melbourne, 145 Studley Road, Heidelberg, Victoria 3084, Australia. Michael.READE@austin.org.au
authors.forename: Michael C
authors.initials: MC
authors.lastname: Reade
authors.forename: Kim
authors.initials: K
authors.lastname: O'Sullivan
authors.forename: Samantha
authors.initials: S
authors.lastname: Bates
authors.forename: Donna
authors.initials: D
authors.lastname: Goldsmith
authors.forename: William R S T J
authors.initials: WR
authors.lastname: Ainslie
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D000328:Adult; D000368:Aged; D003693:Delirium / Q000188:drug therapy* / Q000209:etiology; D020927:Dexmedetomidine / Q000009:adverse effects / Q000627:therapeutic use*; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D007442:Intubation, Intratracheal; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000209:etiology; D012121:Respiration, Artificial
chemical_list: D018492:Dopamine Antagonists; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D006220:Haloperidol