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A Randomized, Double-Blind, Placebo-Controlled Dose Range Study of Dexmedetomidine as Adjunctive Therapy for Alcohol Withdrawal*

Mueller, Scott W. PharmD1; Preslaski, Candice R. PharmD2; Kiser, Tyree H. PharmD, FCCP, FCCM1; Fish, Douglas N. PharmD, FCCP, FCCM1; Lavelle, James C. MD3; Malkoski, Stephen P. MD, PhD3; MacLaren, Robert PharmD, MPH, FCCP, FCCM1

doi: 10.1097/CCM.0000000000000141
Clinical Investigations

Objectives: To evaluate dexmedetomidine as adjunctive therapy to lorazepam for severe alcohol withdrawal.

Design: Prospective, randomized, double-blind, placebo-controlled trial.

Setting: Single center; medical ICU.

Patients: Twenty-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.

Interventions: Patients 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 Results: High-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.

Conclusions: Adjunctive 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.

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.

* See also p. 1298.

This study was performed at the University of Colorado Hospital.

Trial registration: identifier NCT00936377.

An abstract was presented at the European Society of Intensive Care Medicine Annual Meeting, Paris, France, October 9, 2013.

Dr. Mueller’s institution received grant support from Hospira (Dr. Mueller was coinvestigator for this investigator-initiated grant). Hospira had no role in the design of the study or article preparation. Dr. Kiser’s institution received grant support (investigator-initiated research grant). Dr. Fish lectured for Merck, Pfizer, and Forest. His institution received grant support from Hospira (Dr. Fish was coinvestigator for this study) and Merck (grant submission pending). Dr. Lavelle’s institution received grant support from Hospira. Dr. Malkoski’s institution received grant support from Hospira. Dr. MacLaren consulted for Kennedy Childs Law and Rutherford Moore Law and lectured for and received support for the development of educational presentations from American Society of Health-System Pharmacists Advantage. His institution received grant support from Hospira. Dr. Preslaski has disclosed that she does not have any potential conflicts of interest.

Address requests for reprints to: Robert MacLaren, PharmD, MPH, FCCM, FCCP, Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Mail Stop C238, V20-1227, 12850 East Montview Boulevard, Aurora, CO 80045. E-mail:

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins