Original Article

Fixed-Dose Phenobarbital Versus As-Needed Benzodiazepines for the Management of Alcohol Withdrawal in Acute Care General Internal Medicine

Authors: Samuel Hundert, MD, Jillian McLlarky, PharmD, Andrew S. Dunn, MD, MPH, William Markle, PharmD

Abstract

Objectives: The management of patients at risk of severe alcohol withdrawal is challenging because conventional treatment with as-needed benzodiazepines may be ineffective. We created a fixed-dose phenobarbital protocol and compared patient outcomes using this protocol with an as-needed benzodiazepine protocol.

Methods: Patients admitted from the emergency department (ED) to General Medicine from January 1 to June 30, 2022 and treated for alcohol withdrawal with a novel phenobarbital protocol were compared with all of the patients admitted from the ED to General Medicine from January 1 to June 30, 2018, and treated with as-needed benzodiazepines. The primary outcome was a composite of intensive care unit (ICU) transfer or mortality. Secondary outcomes included mortality, ICU transfer, seizure, length of stay, excess sedation, delirium, against medical advice discharge, 30-day re-admission, 30-day ED reevaluation, and antipsychotic use.

Results: There were 54 patients in the phenobarbital group and 197 in the benzodiazepine group. The phenobarbital group was less medically complex but had more risk factors for severe withdrawal. There was no difference in the primary outcome, although there was a trend toward benefit in the phenobarbital group (3.7 vs 8.1%, P = 0.26), and there was a lower incidence of delirium in the phenobarbital cohort (0 vs 8.6%, P = 0.03). Secondary outcome trends favored phenobarbital, with lower mortality, ICU transfer, seizure, oversedation, against medical advice discharge, and 30-day re-admissions. A subgroup analysis accounting for differences in patient populations in the primary analysis found similar results.

Conclusions: Phenobarbital is as safe and effective as benzodiazepine-based protocols for the treatment of high-risk alcohol withdrawal, with lower rates of delirium.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Grant BF, Goldstein RB, Saha TD, et al. Epidemiology of DSM-5 alcohol use disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry 2015;72:757–766.
 
2. Schuckit MA, Danko GP, Smith TL, et al. A 5 year prospective evaluation of DSM-IV alcohol dependence with and without a physiological component. Alcohol Clin Exp Res 2003;27:818–825.
 
3. Schuckit MA. Recognition and management of withdrawal delirium (delirium tremens). N Engl J Med 2014;371:2109–2113.
 
4. Steel TL, Afshar M, Edwards S, et al. Research needs for inpatient management of severe alcohol withdrawal syndrome: an official American Thoracic Society research statement. Am J Respir Crit Care Med 2021; 204:e61–e87.
 
5. Sullivan JT, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 1989;84:1353–1357.
 
6. Saitz R, Mayo-Smith MF, Roberts MS, et al. Individualized treatment for alcohol withdrawal. A randomized double blind controlled trial. JAMA 1994;272:519–523.
 
7. Daeppen JB, Gache P, Landry U, et al. Symptom triggered vs. fixed scheduled doses of benzodiazepines for alcohol withdrawal: a randomized treatment trial. Arch Intern Med 2002;162:1117–1121.
 
8. The ASAM clinical practice guideline on alcohol withdrawal management. J Addict Med 2020;14(3S suppl 1):1–72.
 
9. Patel L, Beddow D, Kirven J, et al. Outcomes of Minnesota Detoxification Scale assessment with high-dose front loading diazepam treatment for alcohol withdrawal in hospitalized patients. Am J Med Sci 2022;363:42–47.
 
10. Devenyi P, Harrison ML. Prevention of alcohol withdrawal seizure with oral diazepam loading. Can Med Assoc J 1985;132:798–800.
 
11. Hyatt M, Cheever T, Eldot R. Diazepam loading for alcohol detoxification. Am J Addict 1996;5:354–358.
 
12. Martin K, Katz A. The role of barbiturates for alcohol withdrawal syndrome. Psychosomatics 2016;57:341–347.
 
13. Nisavic M, Nejad SH, Isenberg BM, et al. Use of phenobarbital in alcohol withdrawal management—a retrospective comparison study of phenobarbital and benzodiazepines for acute alcohol withdrawal management in general medicine patients. Psychosomatics 2019;60: 458–467.
 
14. Rosenson J, Clements C, Simon B, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med 2013;44:592–598.e2.
 
15. Ives TJ, Mooney AJ 3rd, Gwyther RE. Pharmacokinetic dosing of phenobarbital in the treatment of alcohol withdrawal syndrome. South Med J 1991;84:18–21.
 
16. Hawa F, Gilbert L, Gilbert B, et al. Phenobarbital versus lorazepam for management of alcohol withdrawal syndrome: a retrospective cohort study. Cureus 2021;13:e13282.
 
17. Ibarra F Jr. Single dose phenobarbital in addition to symptom triggered lorazepam in alcohol withdrawal. Am J Emerg Med 2020;38:178–181.
 
18. Brothers T, Bach P. Challenges in prediction, diagnosis, and treatment of alcohol withdrawal in medically ill hospitalized patients: a teachable moment. JAMA Intern Med 2020;180:900–901.