Evaluation of phenobarbital based approach in treating patient with alcohol withdrawal syndrome: A systematic review and meta-analysis

Pourmand, Ali; Alremeithi, R.; Kartiko, S.; Bronstein, D.; Tran, Quincy

doi:10.1016/j.ajem.2023.04.002

Cited by 5 publications

(3 citation statements)

References 25 publications

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“… 61 However, there is no evidence that phenobarbital is superior to providing comparable doses of benzodiazepines, 62 and phenobarbital has a relatively narrow therapeutic window. 63 …”

Section: Introductionmentioning

confidence: 99%

Management of alcohol withdrawal syndrome in patients with alcohol-associated liver disease

Ratner,

Blaney,

Rastegar

2024

Hepatology Communications

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Alcohol-associated liver disease is a common and severe sequela of excessive alcohol use; effective treatment requires attention to both liver disease and underlying alcohol use disorder (AUD). Alcohol withdrawal syndrome (AWS) can be dangerous, is a common barrier to AUD recovery, and may complicate inpatient admissions for liver-related complications. Hepatologists can address these comorbid conditions by learning to accurately stage alcohol-associated liver disease, identify AUD using standardized screening tools (eg, Alcohol Use Disorder Identification Test), and assess risk for and symptoms of AWS. Depending on the severity, alcohol withdrawal often merits admission to a monitored setting, where symptom-triggered administration of benzodiazepines based on standardized scoring protocols is often the most effective approach to management. For patients with severe liver disease, selection of benzodiazepines with less dependence on hepatic metabolism (eg, lorazepam) is advisable. Severe alcohol withdrawal often requires a “front-loaded” approach with higher dosing, as well as intensive monitoring. Distinguishing between alcohol withdrawal delirium and HE is important, though it can be difficult, and can be guided by differentiating clinical characteristics, including time to onset and activity level. There is little data on the use of adjuvant medications, including anticonvulsants, dexmedetomidine, or propofol, in this patient population. Beyond the treatment of AWS, inpatient admission and outpatient hepatology visits offer opportunities to engage in planning for ongoing management of AUD, including initiation of medications for AUD and referral to additional recovery supports. Hepatologists trained to identify AUD, alcohol-associated liver disease, and risk for AWS can proactively address these issues, ensuring that patients’ AWS is managed safely and effectively and supporting planning for long-term recovery.

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“… 61 However, there is no evidence that phenobarbital is superior to providing comparable doses of benzodiazepines, 62 and phenobarbital has a relatively narrow therapeutic window. 63 …”

Section: Introductionmentioning

confidence: 99%

Management of alcohol withdrawal syndrome in patients with alcohol-associated liver disease

Ratner,

Blaney,

Rastegar

2024

Hepatology Communications

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“…A meta-analysis of twelve studies and 1934 patients who presented to the ED with AWS analyzed the rate of intubation among patients who received phenobarbital compared with benzodiazepines as the primary outcome and rates of seizures, hospital, and ICU length of stay as secondary outcomes. The results did not differ between the benzodiazepine and phenobarbital groups [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder

Celik,

Gold,

Fuehrlein

2024

Brain Sciences

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Alcohol use disorder (AUD) is a significant contributor to morbidity and mortality in the United States. It contributes to over 140,000 annual deaths, to over 200 related diseases and health conditions globally, and accounts for 5.1% of the global disease burden. Despite its substantial impact, AUD remains undertreated, marked by a scarcity of approved medications. This paper explores the current treatment landscape and novel strategies for both alcohol withdrawal syndrome and AUD. Promising results, including the use of psychedelics alongside psychotherapy, noninvasive neural-circuit-based interventions, phosphodiesterase-4 inhibitors, and GLP-1 receptor agonists, have emerged from recent studies. While these advancements show potential, further research is crucial for a comprehensive understanding of their effectiveness. The clear shortage of approved medications and other treatment modalities underscores the pressing need for ongoing research.

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“…A recent systematic review and meta-analysis reports that there were similar rates of patients requiring intubation, seizures, and length of hospital stay for those who received phenobarbital in comparison to those who were treated with benzodiazepines across intensive care unit (ICU) and ED settings. 25 Prior research examining the efficacy of phenobarbital in ICU settings also shows that phenobarbital may be a safe and effective alternative or adjunct to benzodiazepines. [26][27][28] The Society for Academic Emergency Medicine's (SAEM) Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE) initiative is developing guidelines for reasonable and appropriate care in ED settings 29 and one focus of SAEM GRACE is management of AWS in the ED.…”

Section: Introductionmentioning

confidence: 99%

SAEM GRACE: Phenobarbital for alcohol withdrawal management in the emergency department: A systematic review of direct evidence

Punia,

Scott,

Manuja

et al. 2023

Academic Emergency Medicine

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ObjectivesAlcohol withdrawal syndrome (AWS) is a commonly presenting condition in the emergency department (ED) and can have severe complications, including mortality. Benzodiazepines are first‐line medications for treating AWS, but may be unavailable or insufficient. This systematic review evaluates the direct evidence assessing the utility of phenobarbital for treating AWS in the ED.MethodsA systematic search was conducted and designed according to the patient‐intervention‐control‐outcome (PICO) question: (P) Adults (≥18 years old) presenting to the ED with alcohol withdrawal; (I) Phenobarbital (including adjunctive); (C) Benzodiazepines or no intervention; (O) AWS complications, admission to a monitored setting, control of symptoms, adverse effects, and adjunctive medications. Two reviewers independently assessed articles for inclusion and conducted risk of bias assessments for included studies.ResultsFrom 70 potentially relevant articles, seven studies met inclusion criteria: (three retrospective cohort studies, two retrospective chart reviews, and two randomized controlled trials [RCTs], one examining phenobarbital monotherapy and one examining adjunctive phenobarbital). Across the retrospective cohort studies, treatment of AWS with phenobarbital resulted in lower odds of a subsequent ED visit. The retrospective chart reviews indicated that phenobarbital was associated with higher discharge rate compared to benzodiazepine‐only treatments. For the two RCTs, phenobarbital did not differ significantly from benzodiazepine for most outcomes, although concomitant treatment with phenobarbital was associated with lower benzodiazepine use and intensive care unit admission. The heterogeneous designs and small number of studies prevented quantitative synthesis.ConclusionsRelatively few studies provide direct evidence on the utility of phenobarbital for AWS in the ED, but the evidence that exists generally suggests that it is a reasonable and appropriate approach. Additional RCTs and other methodologically rigorous investigations are needed for more definitive direct evidence.

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Evaluation of phenobarbital based approach in treating patient with alcohol withdrawal syndrome: A systematic review and meta-analysis

Cited by 5 publications

References 25 publications

Management of alcohol withdrawal syndrome in patients with alcohol-associated liver disease

Management of alcohol withdrawal syndrome in patients with alcohol-associated liver disease

A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder

SAEM GRACE: Phenobarbital for alcohol withdrawal management in the emergency department: A systematic review of direct evidence

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