Dexmedetomidine vs. Haloperidol in Delirious, Agitated, Intubated Patients: A Randomised Open-Label Trial

Crit Care. 2009;13(3):R75. doi: 10.1186/cc7890. Epub 2009 May 19.

Abstract

Introduction: 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.

Trial registration: Clinicaltrials.gov NCT00505804.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Delirium / drug therapy*
  • Delirium / etiology
  • Dexmedetomidine / adverse effects
  • Dexmedetomidine / therapeutic use*
  • Dopamine Antagonists / adverse effects
  • Dopamine Antagonists / therapeutic use
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Haloperidol / adverse effects
  • Haloperidol / therapeutic use
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / therapeutic use*
  • Intubation, Intratracheal
  • Male
  • Middle Aged
  • Pilot Projects
  • Psychomotor Agitation / drug therapy*
  • Psychomotor Agitation / etiology
  • Respiration, Artificial*

Substances

  • Dopamine Antagonists
  • Hypnotics and Sedatives
  • Dexmedetomidine
  • Haloperidol

Associated data

  • ClinicalTrials.gov/NCT00505804