Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review

Hammond, Drayton A.; Rowe, Jordan M.; Wong, Adrian; Wiley, Tessa; Lee, Kristen C.; Kane‐Gill, Sandra L.

doi:10.1177/0018578717720310

Cited by 34 publications

(33 citation statements)

References 35 publications

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“…Furthermore, overall safety profiles of barbiturates were comparable to those of BZDs across all studies included. Hammond et al, evaluated patient outcomes associated with phenobarbital use with or without BZDs for AWS by reviewing four controlled trials and five observational studies [ 18 ]. These authors concluded that phenobarbital may have a role in AWS treatment alongside BZDs or as monotherapy.…”

Section: Discussionmentioning

confidence: 99%

Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study

Hawa¹,

Gilbert²,

Gilbert³

et al. 2021

Cureus

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Introduction Annually, 500,000 episodes of alcohol withdrawal syndrome (AWS) are severe enough to require clinical attention. A symptom-triggered lorazepam regimen remains the standard of care for the management of hospitalized AWS patients. However, phenobarbital has also been shown to be an effective adjunctive therapy for severe AWS, reducing benzodiazepine use in the emergency department (ED) and the intensive care unit (ICU). The purpose of this study is to compare hospital length of stay (LOS) for AWS patients using phenobarbital-based versus lorazepam-based treatment protocols as monotherapy for management of AWS on general medical units. Methods This is a retrospective cohort study over a two-year period (March, 2016 to March, 2018), conducted at three hospitals within the St. Joseph Mercy Health System. We included 606 patients with a primary diagnosis of AWS or alcohol intoxication who met our inclusion criteria (543 in the lorazepam cohort and 63 in the phenobarbital cohort). Adjusted comparisons were done using propensity scoring methods. Hospital LOS was set as the primary outcome. Secondary outcomes included all-cause 30-day readmission, alcohol-related 30-day readmission, 30-day ED visits after discharge, and need for ICU transfer during hospital stay. Results Patients who received phenobarbital had a statistically significant shorter hospital LOS as compared to patients who received lorazepam (2.8 versus 3.6 days, P < 0.001). Furthermore, the phenobarbital treatment group had statistically significant lower rates of all-cause 30-day readmission (11.11% versus 14.18%, P = 0.020) and 30-day ED visits after discharge (11.11% versus 18.6%, P = 0.015). No statistical significance was detected for alcohol-related 30-day readmission and the need for ICU transfer between the treatment groups. Conclusion This study suggests that phenobarbital may be a reasonable alternative to lorazepam in the management of AWS patients admitted to general medical units. Larger scale, well-executed, and adequately powered prospective studies and randomized controlled trials are needed to corroborate these findings.

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Section: Discussionmentioning

confidence: 99%

Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study

Hawa¹,

Gilbert²,

Gilbert³

et al. 2021

Cureus

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“…Currently, there are limited data on the use of fixed-dose phenobarbital for the management of AWS in surgical-trauma patients. 27,37 The prevalence of alcohol use in trauma patients has been reported to be as high as 50%. 4,38 However, AWS diagnosis in these patients is relatively low.…”

Section: Discussionmentioning

confidence: 99%

“…Phenobarbital properties, including its long half-life and predictable kinetics, support the use of a fixed-dose regimen approach over a symptom-triggered approach, 23,28,33 especially because the principles of the symptom-triggered approach have not been validated with the use of phenobarbital. 27,37 The efficacy of the symptom-triggered approach relies on frequent assessment of patients’ symptoms using a validated scoring tool and careful attention to the overall condition of the patient by the evaluating clinician. 10 Because scoring tools such as CIWA-Ar and the MINDS rely on a constellation of autonomic signs and subjective symptoms, the presence of other acute illnesses specifically in the ICU might result in increased patients’ scores unrelated to AWS and improper use of the symptom-triggered approach for management of AWS.…”

Section: Discussionmentioning

confidence: 99%

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Phenobarbital Monotherapy for the Management of Alcohol Withdrawal Syndrome in Surgical-Trauma Patients

Ammar

Rosen

et al. 2020

Ann Pharmacother

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Background Benzodiazepine is first-line therapy for alcohol withdrawal syndrome (AWS), and phenobarbital is an alternative therapy. However, its use has not been well validated in the surgical-trauma patient population. Objective To describe the use of fixed-dose phenobarbital monotherapy for the management of patients at risk for AWS in the surgical-trauma intensive care unit. Methods Surgical-trauma critically ill patients who received phenobarbital monotherapy, loading dose followed by a taper regimen, for the management of AWS were included in this evaluation. The effectiveness of phenobarbital monotherapy to treat AWS and prevent development of AWS-related complications were evaluated. Safety end points assessed included significant hypotension, bradycardia, respiratory depression, and need for invasive mechanical ventilation. Results A total of 31 patients received phenobarbital monotherapy; the majority of patients were at moderate risk for developing AWS (n = 20; 65%) versus high risk (n = 11; 35%). None of the patients developed AWS-related complications; all patients were successfully managed for their AWS. Nine patients (29%) received nonbenzodiazepine adjunct therapy for agitation post–phenobarbital initiation. Three patients (10%) experienced hypotension, and 3 (10%) were intubated. None of the patients had clinically significant bradycardia or respiratory depression. Conclusion and Relevance Fixed-dose phenobarbital monotherapy appears to be well tolerated and effective in the management of AWS. Further evaluation is needed to determine the extent of benefit with the use of phenobarbital monotherapy for management of AWS.

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“…Alcohol (ethanol) is a central nervous system depressant, which triggers an adaptive process and the molecular changes associated with tolerance leading to imbalance of excitation and inhibition (Olsen and Spigelman, 2012). This molecular change in network leads to a wide range of complications, such as a neuroexcitatory effect, that plays an important role in AWS and may contribute to increased LOS and mortality (Connor et al, 2016;Hammond et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

The maximum alcohol withdrawal syndrome score associates with worse clinical outcomes—A retrospective cohort study

Griessbach

Mueller

Battegay

et al. 2019

Drug and Alcohol Dependence

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Background: The Wetterling alcohol withdrawal syndrome (AWS) scale determines withdrawal severity and guides treatment. We investigated associations between maximum AWS scores and clinical outcomes. Methods: This retrospective cohort study considered AWS assessments measured from 8/2015-8/2017. We used multivariable linear and logistic regression to analyze associations between the maximum score and increased length of stay (LOS) and in-hospital mortality, respectively. Firstly, we investigated the maximum score of all AWS assessments any time during the stay, secondly, the maximum measured only within the first 3 days of withdrawal. Results: A total of 2,464 hospital stays showed that, patients with "mild" (<6), "moderate" (6-9), and "severe" (>9) maximum scores had median LOS of 5.93, 9.35, 14.71 days, mortality was 1.7%, 4.8%, 8.0%, respectively. Regression showed that a higher maximum score was independently associated with increased LOS and mortality (both p < 0.001). Based on the maximum AWS score within the first 3 days, the median LOS was 6.18, 9.00, 12.89 days, mortality was 2.2%, 3.6%, 7.6%, respectively. A higher maximum score in the first 3 days was independently associated with increased LOS (p = 0.036) and mortality (p = 0.001). Severe maximum AWS scores within 3 days of withdrawal had an odds ratio of 2.53 (95% CI: 1.27, 4.82; p = 0.0060) for in-hospital death. Conclusions: Maximum AWS scores associate independently with increased LOS and in-hospital mortality. This association is reproducible within the first 3 days of withdrawal. Development of such a 3-day tool could help clinicians assess the risk of worse clinical outcomes early on and adjust care accordingly.

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Patient Outcomes Associated With Phenobarbital Use With or Without Benzodiazepines for Alcohol Withdrawal Syndrome: A Systematic Review

Cited by 34 publications

References 35 publications

Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study

Phenobarbital Versus Lorazepam for Management of Alcohol Withdrawal Syndrome: A Retrospective Cohort Study

Phenobarbital Monotherapy for the Management of Alcohol Withdrawal Syndrome in Surgical-Trauma Patients

The maximum alcohol withdrawal syndrome score associates with worse clinical outcomes—A retrospective cohort study

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