Phenobarbital Protocol for Alcohol Withdrawal Syndrome
Benzodiazepines remain the gold standard for alcohol withdrawal treatment, but phenobarbital is a safe and effective alternative that may be particularly useful in patients with severe withdrawal or benzodiazepine resistance. 1
Assessment and Indications
Use the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) to assess AWS severity:
- Score >8: Moderate AWS
- Score ≥15: Severe AWS
- Note: CIWA-Ar may be inaccurate in patients with anxiety disorders, sepsis, hepatic encephalopathy, or severe pain 1
Indications for inpatient treatment with phenobarbital:
- Severe AWS
- History of withdrawal seizures or delirium tremens
- Concurrent serious physical or psychiatric illness
- Failure of outpatient treatment
- Inadequate response to benzodiazepines 1
Phenobarbital Protocol
Dosing Options:
Fixed-dose protocol:
- Initial loading dose: 100-200 mg IM if signs of withdrawal occur on first day
- Maintenance: 30 mg PO for each 100-200 mg of barbiturate the patient was taking
- Total daily dose: Divided into 3-4 doses, not to exceed 600 mg daily
- Tapering: Decrease by 30 mg/day as long as withdrawal is proceeding smoothly 2
Symptom-triggered protocol:
- Typical MICU dosing: Average of 1977.5 mg (±1531.5 mg) during ICU stay
- Titrate to goal Richmond Agitation Sedation Scale (RASS) score of 0 to -1 3
Administration and Monitoring:
- Monitor vital signs frequently, especially in severe withdrawal
- Assess for respiratory depression, particularly in patients with underlying pulmonary disease
- Evaluate for hypotension, which may occur at higher doses
- Monitor for signs of excessive sedation
- Ensure airway protection before administration in patients with altered mental status 1
Adjunctive Treatments
Thiamine supplementation:
- Prevention of Wernicke encephalopathy: 100-300 mg/day for 4-12 weeks
- Management of Wernicke encephalopathy: 100-500 mg/day for 12-24 weeks
- Administer thiamine before giving IV fluids containing glucose 1
Supportive care:
- Fluid and electrolyte replacement (especially magnesium)
- Comfortable environment
- Psychiatric consultation for evaluation, treatment, and long-term planning of alcohol abstinence 1
Advantages of Phenobarbital
- Longer half-life than benzodiazepines
- Anti-glutamate activity in addition to GABA effects
- May be effective in benzodiazepine-resistant cases
- Lower rates of delirium compared to benzodiazepines (0% vs 8.6%) 4, 5
- May reduce hospital length of stay (mean difference -2.6 days) 6
Cautions and Contraindications
- Risk of respiratory depression, especially when combined with other CNS depressants
- Potential for oversedation requiring mechanical ventilation
- Lethal dose is far less if alcohol is also ingested
- Use with caution in patients with:
Withdrawal Management
For patients dependent on barbiturates/phenobarbital:
- Minor withdrawal symptoms appear 8-12 hours after last dose
- Major withdrawal symptoms (convulsions, delirium) may occur within 16 hours and last up to 5 days
- Withdrawal intensity gradually declines over approximately 15 days
- Withdrawal symptoms can be severe and potentially fatal 2
Key Pitfalls to Avoid
Do not use antipsychotics as stand-alone medications for AWS management; they should only be used as adjuncts to benzodiazepines or phenobarbital in severe withdrawal delirium not responding to adequate doses 1
Do not use anticonvulsants following an alcohol withdrawal seizure for prevention of further seizures 1
Avoid combining phenobarbital with large doses of benzodiazepines without careful monitoring due to risk of excessive sedation
Do not administer IV glucose before thiamine, as this may precipitate acute thiamine deficiency 1
Avoid abrupt discontinuation of phenobarbital in patients who have been receiving it for more than a few days