Original Contributions
Phenobarbital for Acute Alcohol Withdrawal: A Prospective Randomized Double-blind Placebo-controlled Study

https://doi.org/10.1016/j.jemermed.2012.07.056Get rights and content

Abstract

Background

Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management.

Objective

We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal.

Methods

This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward).

Results

There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4–32). There were no differences in adverse events.

Conclusions

A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes.

Introduction

Small studies have investigated use of phenobarbital for treatment of acute alcohol withdrawal 1, 2, 3. The longer half-life of phenobarbital compared to lorazepam may be a clinical advantage in the treatment of acute alcohol withdrawal (4). The lack of prospective data regarding use of phenobarbital for alcohol withdrawal leaves clinicians basing their use of phenobarbital for acute alcohol withdrawal on limited or anecdotal evidence.

Acute alcohol withdrawal is encountered in patients presenting acutely to the Emergency Department (ED). There are likely in excess of 8 million alcohol-dependent people in the United States; every year, approximately 500,000 episodes of acute alcohol withdrawal syndrome (AAWS) require pharmacologic management (5). AAWS results in a significant utilization of health care resources, particularly in safety-net and emergency health care settings.

We hypothesized that a single dose of intravenous (i.v.) phenobarbital combined with a standardized, symptom-guided lorazepam-based alcohol withdrawal protocol would result in decreased intensive care unit (ICU) admission.

Section snippets

Study Design

This was a prospective, randomized, double-blind, placebo-controlled study of ED patients with AAWS admitted to the hospital with a primary admission diagnosis of alcohol withdrawal (International Classification of Diseases, 9th Revision [ICD-9] code 291.81). All study investigators, enrolling providers, nursing staff, statisticians, and research assistants were blinded to group allocation for the duration of the study. Unblinding occurred after completion of data analysis. The study

Results

During the study period from January 2009 to March 2010, 460 patients presented to the ED with acute alcohol withdrawal. There were 198 patients enrolled during the study period, and 102 met inclusion criteria for analysis. Thirty subjects (59%) in the phenobarbital group and 32 patients (63%) in the placebo group initially waived consent and were subsequently consented and included in the analysis (Figure 1).

Fifty-one patients were randomized to receive phenobarbital and 51 received placebo.

Discussion

A single dose of i.v. phenobarbital resulted in decreased ICU admission rate, decreased use of continuous lorazepam infusion, and was not associated with increased adverse events. Phenobarbital has been cited as a second-line agent for AAWS and other conditions for which benzodiazepines are considered first-line treatment, such as status epilepticus. Our study provides further evidence to support use of phenobarbital as an adjunct to benzodiazepines for AAWS and also provides evidence that

Conclusions

A single dose of i.v. phenobarbital resulted in decreased ICU admission rate, decreased use of continuous lorazepam infusion, and was not associated with increased adverse events. Given the morbidity, mortality, and financial cost burden of acute alcohol withdrawal, the potential benefit of i.v. phenobarbital for AAWS warrants further study.

Article Summary

1. Why is this topic important?

  1. Acute alcohol withdrawal syndrome is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management.

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