Organizers and Facilitators: James Wiley, Valerie Vaughn, Julia Symczak, Andrew Auerbach, Jeff Schnipper, Sunil Kripalani, James Harrison

Background

Mild to moderate alcohol withdrawal syndrome (AWS) is usually treated with benzodiazepine symptom-triggered therapy, but recently, phenobarbital has gained popularity due to favorable pharmacokinetics (loading dose and long half-life) and perceived better control of AWS. Currently, no guidelines recommend phenobarbital as a first-line treatment, and there is a lack of prospective data comparing phenobarbital to benzodiazepine therapy.

We propose studying phenobarbital versus benzodiazepines in AWS and discussed this topic on a HOMERuN Collaborative call. We present the key findings from our discussion.

Importance of Studying Inpatient Treatment

Hospitalists consistently felt this study is essential because evidence exists for AWS treatment in ICU and ED settings but is lacking for acute medical and surgical floors. Phenobarbital use is often restricted to ICU or ED settings only due to this lack of evidence. Provider preferences appear to be the primary driver of therapy, and there is a lack of consensus among providers or care settings (ED vs. ICU vs. Floor) on how to best treat AWS. There is a belief among some hospitals that have switched to phenobarbital that it is superior to benzodiazepine for treatment of withdrawal, but evidence remains lacking.

"I think our challenge has been the lack of data on floor patients…it's a bit of a mishmash right now and so the confusion is a problem. The nurses don’t know what to do, the residents don't know what to do — it's basically the wild west again."

Primary Focus on Health System Outcomes

Hospitalists are primarily focused on outcomes that focus on the logistics of care for AWS patients, such as the length of stay, ICU utilization, and the nursing care burden of AWS associated with phenobarbital and benzodiazepines. Hospitalists are also interested in whether benzodiazepine compared to phenobarbital resulted in more complications, respiratory suppression, higher rates of 30-day readmissions, more prescriptions of medications for alcohol use disorder and more outpatient appointments for substance use disorder on discharge.

"Even if the outcomes were non-inferior, I think there's an argument to be made that if there was good clinician and nursing buy-in and it was easy to use and those kinds of things, then if it's non-inferior to benzos and it's overall something that the clinical team likes more, then that's impactful too."

Lack of Engaging Patients in Shared Decision-making

Providers rarely offer shared decision-making around the choice of inpatient withdrawal treatment. Withdrawal severity or medication contraindications are what drive most treatment decisions. At hospitals that have both a benzodiazepine and phenobarbital protocol, some choice is offered to patients when clinically appropriate. However, given that most hospitals do not have both protocols, offering choices to patients is not possible. Systems level (e.g., hospital protocols) factors often drive medication choices.

"I don't think I've ever asked a patient which medication they wanted to use for their withdrawal. I do feel like that's probably what a lot of people are doing. I think it is difficult because they're often coming in not really able to engage in that discussion with you and a lot of us really only have one way of doing things, so we're not really able to even present options to them."

Concerns

• The primary concerns for any study involving AWS focused on ensuring consistent treatment allocation throughout an AWS stay and the ability of patients to consent to participate in the study.
• AWS spans multiple levels of care (e.g., ED/Floor/ICU), and there is concern about the ability to obtain buy-in from all care settings and ensure consistent therapy across these settings.
• Consent is a significant concern for any study of alcohol withdrawal syndrome due to the population often being vulnerable and not able to participate in any discussion of risk or benefits when experiencing acute withdrawal or acute intoxication.

"The ER starts the patients on these treatments, and then they get admitted overnight to us. By the time I see them, it's the next morning and they've already gotten several doses of whatever was given in the ER. It's really hard to then derail that plan because it's already in motion."

Conclusion

There is significant interest in studying AWS treatment for moderate to severe withdrawal in the inpatient setting due to the current lack of conclusive evidence. Treatment outcomes should include both hospital system and patient-oriented measures. AWS treatment is lacking in shared decision-making for hospitalized patients. Challenges to conducting an AWS trial include the inability to consent patients who are in withdrawal or intoxicated, and the need to obtain buy-in from different provider groups from different care settings (e.g., (ED/ICU/Floor).

Related Publication

This practical open access article describes an approach and outcomes around use of phenobarbital for alcohol withdrawal at a University of Washington hospital.

Wolpaw BJ, Oren H, Quinnan-Hostein L, et al. Hospital-Wide Implementation, Clinical Outcomes, and Safety of Phenobarbital for Alcohol Withdrawal. JAMA Netw Open. 2025;8;(8):e2528694.

AHRQ is currently recruiting acute care hospital units for a free 9-month program to implement and improve evidence-based practices for prevention of catheter-associated urinary tract infections (CAUTI). Units will receive training and one-on-one expert coaching to implement sustainable improvements to their infection prevention practices. You're welcome to join an informational webinar to learn more; the schedule is below.

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