Safety of Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal in Critically Ill Patients With Primary Neurologic Injuries

Author:

Deveau Robert12,Wong Adrian1ORCID,Eche Mary1ORCID,Yankama Tuyen1,Fehnel Corey R.345

Affiliation:

1. Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, MA, USA

2. Department of Pharmacy, Rhode Island Hospital, Providence, RI, USA

3. Division of Neurocritical Care and Hospital Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA

4. Hebrew SeniorLife, Marcus Institute for Aging Research, Boston, MA

5. Harvard Medical School, Boston, MA

Abstract

Background: Alcohol withdrawal syndrome (AWS) is a complication of alcohol use disorder that manifests as a range of symptoms. Symptom-triggered benzodiazepines (BZDs) are often used as first-line treatment of AWS. However, recent literature suggests phenobarbital (PHB) may be safer and more efficacious, but studies are limited by exclusion of patients with neurological injuries. Objective: We aimed to evaluate the safety of PHB compared to BZDs for the management of AWS among patients with primary neurologic injuries. Methods: Retrospective cohort study of patients with primary neurologic injuries admitted to an ICU who received PHB or symptom-triggered BZD for AWS between December 2013 and February 2020. The primary outcome was incidence of oversedation, defined as Richmond Agitation Sedation Scale (RASS) scores from −5 to −3 within 24 hours of initial PHB or BZD dose. Secondary outcomes included largest decrease in RASS, need for mechanical ventilation, and additional sedative use within 24 hours of initial PHB or BZD dose. A multivariable analysis was performed to evaluate the association of PHB administration with the primary outcome. Results: Among 600 patients treated for AWS, 84 patients were included in our analysis (PHB, n = 56; BZD, n = 28). In the unadjusted analysis, there were no differences between the PHB and BZD groups for the primary outcome of oversedation (21.4 vs. 7.1%, P = 0.13), or secondary outcomes of decrease in RASS ( P = 0.34), or new ventilator requirement ( P = 0.55). Patients who received PHB had higher rates of additional sedative use ( P < 0.01). Multivariable regression revealed an increase in oversedation among intubated patients ( P = 0.014), while PHB administration was not independently associated with oversedation ( P = 0.516). Conclusion and Relevance Phenobarbital did not independently increase the risk of oversedation compared to BZD for AWS in patients with primary neurologic injuries. Future studies should determine optimal dosing of PHB in this population.

Funder

national institutes of health

Publisher

SAGE Publications

Reference19 articles.

1. Alcohol Withdrawal Syndrome in Neurocritical Care Unit: Assessment and Treatment Challenges

2. Alvanzo A, Kleinschmidt K, Kmiec J, et al The ASAM clinical practice guideline on alcohol withdrawal management. American Society of Addiction Medicine. Published January 2020. Accessed September 3, 2023. https://downloads.asam.org/sitefinity-production-blobs/docs/default-source/quality-science/the_asam_clinical_practice_guideline_on_alcohol-1.pdf?sfvrsn=ba255c2_0

3. A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens*

4. Phenobarbital for Acute Alcohol Withdrawal Management in Surgical Trauma Patients—A Retrospective Comparison Study

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