Phenobarbital for the Management of Alcohol Withdrawal Syndrome in Critically Ill, Surgical-Trauma Patients

Published:December 09, 2022DOI:



      While benzodiazepines (BZD) are the standard of care therapy for the management alcohol withdrawal syndrome (AWS), phenobarbital (PHB) is often used as an alternative agent. The objective of this study is to assess the use of PHB therapy for the management of AWS in trauma-surgical intensive care unit (TSCU) patients.

      Materials and methods

      This is an institutional review board–approved single-center, retrospective study conducted at a large academic medical center. Patients aged ≥ 18 y admitted to the TSCU receiving PHB therapy for primary management of AWS were included. The primary outcome evaluated was the incidence of AWS-related complications (AWSRC) defined as severe agitation, delirium tremens, or seizures following initiation of PHB. Secondary outcomes included the incidence of oversedation and duration of mechanical ventilation.


      Sixty patients were included in this study. AWSRC following initiation of PHB occurred in 65% of patients. Median time to initiation of PHB (42 versus 18 h, P = 0.001) and rates of oversedation (79.5% versus 28.6%, P < 0.001) were significantly greater among patients who experienced AWSRC compared to those who did not. Univariate analysis revealed use of BZD therapy for ≥ 24 h prior to PHB initiation, time from hospital admission to PHB initiation ≥ 24 h, presence of AWS symptoms at baseline, and baseline MINDS score > 6 were risk factors for AWSRC.


      Delays in initiation of PHB appear to be associated with an increased risk for developing AWSRC. Further research is needed to identify an optimal dosing strategy for TSCU patients at high risk for severe AWS.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Carlson R.W.
        • Kumar N.N.
        • Wong-Mckinstry E.
        • et al.
        Alcohol withdrawal syndrome.
        Crit Care Clin. 2012; 28: 549-585
        • Sarff M.C.
        • Gold J.A.
        Alcohol withdrawal syndromes in the intensive care unit.
        Crit Care Med. 2010; 38: S494-S501
        • Bayard M.
        • Mcintyre J.
        • Hill K.R.
        • et al.
        Alcohol withdrawal syndrome.
        Am Fam Physician. 2004; 69: 1443-1450
        • Schukit M.A.
        Recognition and management of withdrawal delirium (delirium tremens).
        N Engl J Med. 2014; 371: 2109-2113
        • Nisavic M.
        • Nejad S.H.
        • Isenberg B.M.
        • et al.
        Use of phenobarbital in alcohol withdrawal management – a retrospective comparison study of phenobarbital and benzodiazepines for acute alcohol withdrawal management in general medical patients.
        Psychosomatics. 2019; 60: 458-467
        • Tidwell W.P.
        • Thomas T.L.
        • Pouliot J.D.
        • Canonico A.E.
        • Webber A.J.
        Treatment of alcohol withdrawal syndrome: phenbobarbital vs. CIWA-Ar protocol.
        Am J Crit Care. 2018; 27: 454-461
        • Nelson A.C.
        • Kehoe J.
        • Sankoff J.
        • Mintzer D.
        • Taub J.
        • Kaucher K.A.
        Benzodiazepines vs barbiturates for alcohol withdrawal: analysis of 3 different treatment protocols.
        Am J Emerg Med. 2019; 37: 733-736
        • Nejad S.
        • Nisavic M.
        • Larentzakis A.
        • et al.
        Phenobarbital for acute alcohol withdrawal management in surgical trauma patients – a retrospective comparison study.
        Psychosomatics. 2020; 61: 327-335
        • Quarshi F.
        • Powell J.
        • Amoateng R.B.
        • et al.
        Geriatric trauma patients with alcohol withdrawal: current overview.
        J Am Med Dir Assoc. 2022; 23: 701-702
        • Ammar M.A.
        • Ammar A.A.
        • Rosen J.
        • Kassab H.S.
        • Becher R.D.
        Phenobarbital monotherapy for the management of alcohol withdrawal syndrome in surgical-trauma patients.
        Ann Pharmacother. 2021; 53: 294-302
        • Goodberlet M.
        • Dube K.
        • Kovacevic M.
        • Szumita P.
        • DeGrado J.
        Evaluation of a phenobarbital-based protocol for severe alcohol withdrawal in critically ill patients.
        Hosp Pharm. 2020; 56: 550-559
        • Hammond D.A.
        • Rowe J.M.
        • Wong A.
        • Wiley T.L.
        • Lee K.C.
        • Kane-Gill S.L.
        Patient outcomes associated with phenobarbital use with or without benzodiazepines for alcohol withdrawal syndrome: a systematic review.
        Hosp Pharm. 2017; 52: 607-616
      1. Phenobarbital. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc, Riverwoods, IL2021
        • Oks M.
        • Cleven K.L.
        • Healy L.
        • et al.
        The safety and utility of phenobarbital use for the treatment of severe alcohol withdrawal syndrome in the medical intensive care unit.
        J Intensive Care Med. 2020; 35: 844-850
        • Lukan J.K.
        • Reed D.N.
        • Looney S.W.
        • Spain D.A.
        • Blondell R.D.
        Risk factors for delirium tremens in trauma patients.
        J Trauma. 2002; 53: 901-907
        • Jawa R.S.
        • Stothert J.C.
        • Shostrom V.K.
        • et al.
        Alcohol withdrawal syndrome in admitted trauma patients.
        Am J Surg. 2014; 208: 781-787
        • Farrokh S.
        • Roels C.
        • Owusu K.A.
        • et al.
        Alcohol withdrawal syndrome in neurocritical care unit: assessment and treatment challenges.
        Neurocrit Care. 2021; 34: 593-607
        • Duby J.J.
        • Berry A.J.
        • Ghayyem P.
        • Wilson M.D.
        • Cocanour C.S.
        Alcohol withdrawal syndrome in critically ill patients: protocolized vs non-protocolized management.
        J Trauma Acute Care Surg. 2014; 77: 938-943
        • Daeppen J.B.
        • Gache P.
        • Landry U.
        • et al.
        Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial.
        Arch Intern Med. 2002; 162: 1117-1121
        • Ives T.J.
        • Mooney A.J.
        • Gwyther R.E.
        Pharmacokinetic dosing of phenobarbital in the treatment of alcohol withdrawal syndrome.
        South Med J. 1991; 84: 18-21