• Scott W Mueller, Candice R Preslaski, Tyree H Kiser, Douglas N Fish, James C Lavelle, Stephen P Malkoski, and Robert MacLaren.
• 1Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO. 2Department of Pharmacy, Denver Health Medical Center, Denver, CO. 3Division of Pulmonary and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO.
• Crit. Care Med.. 2014 May 1;42(5):1131-9.

ObjectivesTo evaluate dexmedetomidine as adjunctive therapy to lorazepam for severe alcohol withdrawal.DesignProspective, randomized, double-blind, placebo-controlled trial.SettingSingle center; medical ICU.PatientsTwenty-four adult patients with a Clinical Institute Withdrawal Assessment score greater than or equal to 15 despite greater than or equal to 16 mg of lorazepam over a 4-hour period.InterventionsPatients received a symptom-triggered Clinical Institute Withdrawal Assessment protocol with lorazepam and were randomized to dexmedetomidine 1.2 μg/kg/hr (high dose), 0.4 μg/kg/hr (low dose), or placebo as adjunctive therapy for up to 5 days or resolution of withdrawal symptoms.Measurement And Main ResultsHigh-dose and low-dose groups were combined as a single dexmedetomidine group for primary analysis with secondary analysis exploring a dose-response relationship. The difference in 24-hour lorazepam requirements after versus before study drug was greater in the dexmedetomidine group compared with the placebo group (-56 mg vs -8 mg, p = 0.037). Median differences were similar for high dose and low dose. The 7-day cumulative lorazepam requirements were not statistically different between dexmedetomidine and placebo (159 mg vs 181 mg). Clinical Institute Withdrawal Assessment or Riker sedation-agitation scale scores representing severe agitation (13% vs 25%) or moderate agitation (27% vs 22%) within 24 hours of initiating study drug were similar for dexmedetomidine and placebo groups, respectively. Bradycardia occurred more frequently in the dexmedetomidine group versus placebo group (25% vs 0%, p = not significant), with the majority of bradycardia occurring in the high-dose group (37.5%). Study drug rate adjustments occurred more often in the dexmedetomidine group compared with the placebo group (50% vs 0%, p = 0.02). Neither endotracheal intubation nor seizure occurred in any group while on study drug.ConclusionsAdjunctive dexmedetomidine for severe alcohol withdrawal maintains symptom control and reduces lorazepam exposure in the short term, but not long term, when using a symptom-triggered protocol. Monitoring for bradycardia is needed with dexmedetomidine but the occurrence may be lessened with low dose. Further study is needed to evaluate the clinical impact of dexmedetomidine.

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