Alcohol use disorder, or heavy drinking, is commonly seen in patients who present to trauma centers. These patients are at risk for Alcohol Withdrawal Syndrome (AWS), which is collection of symptoms that can range from anxiety and restlessness to seizures, delirium and even death. The Clinical Institute Withdrawal Assessment (CIWA) tool is routinely used to assess alcohol withdrawal symptoms. Benzodiazepines (BZD) are commonly administered to trauma patients who exhibit symptoms of AWS based on the CIWA scoring system. Although these medications have proven efficacy, they can also have negative side effects which may affect recovery. Valprate (VPA) is a medication which may have efficacy in management of AWS symptoms, thus ameliorating or preventing the need for BZD administration. This trial will study the effectiveness of VPA in the prevention of AWS symptoms by comparing the amount of BZD use in trauma patients who receive BZD treatment as indicated by CIWA scores with patients who receive prophylactic VPA therapy in addition to BZD as indicated by CIWA scores.

Alcohol use disorder is a common comorbidity among trauma patients. This pre-existing condition is associated with Alcohol Withdrawal Syndrome (AWS) and frequently complicates the management of this patient population. Current treatment and/or prevention of AWS includes the administration of sedatives (benzodiazepines [BZD]) in response to the manifestation AWS symptoms. This manifestation is indicated by monitoring patients using the Clinical Institute Withdrawal Assessment (CIWA) tool. Benzodiazepines elicit an effect on AWS via mediation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Benzodiazepines, however, have the potential to promote multiple negative effects in the acute care setting, including increased incidence of delirium, hospital stay, mortality, and the potential for decreased long-term cognitive function. The antiepileptic medication valproate (VPA) also has GABA activity in the brain, but may be less likely to promote the negative effects associated with BZDs. Currently, previous experience with this agent for the prevention of AWS is limited to two small studies. In these studies VPA was shown to decrease symptoms of AWS as indicated by patients' CIWA scores. Therefore, VPA could serve as an efficacious adjuvant therapy for the prevention of AWS. The aim of this study is to determine whether VPA will decrease the use of BZD in patients who are receiving symptom-based preventative therapy via CIWA monitoring. The hypothesis is that VPA will decrease the utilization of symptom-based lorazepam administration in patients who are determined to be at risk of alcohol withdrawal due to routine consumption of alcohol.

The purpose of this study is to determine if prophylactic VPA for the prevention of alcohol withdrawal syndrome can decrease symptom-triggered use of benzodiazepines in patients monitored for alcohol withdrawal syndrome with the CIWA.

The Primary objective of this study is to determine if prophylactic VPA acid is associated with decreased lorazepam use in patients monitored for alcohol withdrawal syndrome with the CIWA.

Secondary objectives are:

To evaluate the difference between comparator arms with respect to:

• CIWA scores between patients with and without VPA prophylaxis
• Hospital and Intensive Care Unit (ICU) length of stay
• In-hospital mortality
• VPA acid associated side effects (e.g. thrombocytopenia, transaminitis, pancreatitis)

This will be single-center prospective, randomized study, enrolling trauma patients with a history of alcohol consumption admitted to a Level 1 trauma center. Patients included in this study will receive standard therapies for AWS practiced at study institution which include monitoring of withdrawal symptoms and the administration of BZDs (lorazepam) based on CIWA monitoring.

Following informed consent, patients will be randomized to receive CIWA protocol monitoring/BZD or CIWA protocol monitoring/BZD and VPA. Therefore, patients that meet the inclusion criteria will be separated into two study groups to compare outcomes:

1. Treatment Group: Patients treated with CIWA protocol/BZD and VPA
2. Control Group: Patients treated with CIWA protocol/BZD only.

Inclusion Criteria:

• Admission to Trauma Services

• Heavy drinkers based on social history

  • Men <65 years: > 4 drinks per day or 14 per week
  • Women: > 3 drinks per day or 7 drinks per week
  • All adults >65 years: > 3 drinks per day or 7 drinks per week

• Moderate or severe alcohol use disorder based on social history and DSM-5 criteria

  • Moderate: Presence of 4-5 symptoms based on social history
  • Severe: Presence of 6 symptoms based on social history

Exclusion Criteria:

• Intubated patients
• Glasgow Coma Score <8
• Grade IV liver laceration or greater
• Child-Pugh Class B or greater, history of cirrhosis, or cirrhosis identified by radiographic imaging upon admission
• Transaminase (AST/ALT) elevation of ≥ 2x normal
• Anticipated admission less than 72 hours
• Levetiracetam administration for seizure prophylaxis secondary to a traumatic brain injury
• Patient with VPA as home medication
• Known allergy to VPA
• Patients with pre-existing blood dyscrasias, i.e. thrombocytopenia (platelet count < 50,000, etc)
• Inability to obtain social history from patient, surrogate, family member or an individual deemed to be knowledgeable about the patient's social history
• Pregnancy