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PEDIATRICS

Withdrawal from Lorazepam in Critically Ill Children

Assistant Professor of Pharmacy, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM

Mark R Crowley, MD

Associate Professor of Pediatrics, Department of Pediatrics, University of New Mexico Health Sciences Center

Denise M Coleman, MD

Associate Professor of Pediatrics, Department of Pediatrics, University of New Mexico Health Sciences Center

Robert W Katz, MD

Professor of Pediatrics, Department of Pediatrics, University of New Mexico Health Sciences Center

Diana G Wilkins, PhD

Research Associate Professor of Pharmacology and Toxicology, Center for Human Toxicology, University of Utah Health Sciences Center, Salt Lake City, Utah

H William Kelly, PharmD

Professor Emeritus of Pediatrics, Department of Pediatrics, University of New Mexico Health Sciences Center

Reprints: Dr. Dominguez, College of Pharmacy, University of New Mexico Health Sciences Center, MSC09 5360, 1 University of New Mexico Albuquerque, NM 87131-0001, fax 505/272-4721, kdominguez{at}salud.unm.edu

BACKGROUND: Sedatives are used in critically ill children to facilitate mechanical ventilation. Although tolerance and withdrawal are associated with use of sedatives, information about withdrawal from benzodiazepines in children is limited.

OBJECTIVE: To document the occurrence of lorazepam withdrawal in critically ill children and identify predictors for the development of withdrawal.

METHODS: This prospective, investigational, open-label study enrolled pediatric patients receiving a continuous infusion of lorazepam for at least 72 hours. The lorazepam dosage was tapered in a uniform fashion over 6 days by decreasing the total daily dose by 50% every other day on 3 occasions; it was then discontinued. The occurrence of withdrawal from lorazepam was determined by pediatric intensive care unit attending physicians based on clinical judgment. Patients were assessed for withdrawal twice daily beginning 48 hours after the initiation of the lorazepam taper. Assessments were continued for 72 hours after lorazepam discontinuation or until the patient experienced withdrawal, whichever came first. Patient demographic, sedative dosing, and lorazepam serum concentration data were collected to identify risk factors for withdrawal.

RESULTS: Twenty-nine patients completed the study. They received lorazepam for a median duration of about 21 days, and withdrawal occurred in 7 patients. There were no significant differences in demographic variables, lorazepam dosage or other sedative therapy, or lorazepam serum concentrations between patients with withdrawal and those without withdrawal. No predictors of withdrawal were identified.

CONCLUSIONS: Withdrawal occurred in 24% of critically ill children receiving long-term sedation from lorazepam. Risk factors for withdrawal are unknown.

Key Words: benzodiazepines, critical care, lorazepam, pediatrics, sedatives, substance withdrawal syndrome

Published Online, May 23, 2006. www.theannals.com, DOI 10.1345/aph.1G701

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