What is the recommended inpatient protocol for using phenobarbital to manage alcohol withdrawal syndrome?

Phenobarbital Protocol for Inpatient Management of Alcohol Withdrawal Syndrome

While benzodiazepines remain the gold standard for alcohol withdrawal syndrome (AWS) management, phenobarbital is a safe and effective alternative that may be particularly beneficial for patients with severe AWS or those not responding to benzodiazepines. 1, 2

Patient Selection for Phenobarbital Protocol

• Indications for inpatient phenobarbital treatment:
  • Severe AWS (CIWA-Ar score ≥15)
  • History of withdrawal seizures or delirium tremens
  • Failed outpatient treatment
  • Benzodiazepine-refractory withdrawal
  • Significant medical or psychiatric comorbidities
  • Liver dysfunction (phenobarbital may be safer than long-acting benzodiazepines)

Initial Assessment and Monitoring

• Assess AWS severity using CIWA-Ar scale (score >8 indicates moderate AWS; ≥15 indicates severe AWS)
• Monitor vital signs frequently (every 1-2 hours initially)
• Evaluate for comorbidities: dehydration, electrolyte imbalances, infection, head trauma, GI bleeding
• Obtain baseline labs: comprehensive metabolic panel, magnesium level, CBC

Phenobarbital Dosing Protocol

Loading Dose Approach:

1. Initial loading dose: 10 mg/kg IV (typically 650-1000 mg for average adult)

   • Administer over 30 minutes to avoid respiratory depression
   • This achieves therapeutic levels quickly for severe withdrawal

2. Maintenance dosing:

   • 130-260 mg IV/PO every 6-8 hours as needed based on symptoms
   • Taper over 3-5 days as withdrawal symptoms resolve

Symptom-Triggered Approach:

• For moderate AWS (CIWA-Ar 8-14): 130-260 mg PO/IV every 6 hours as needed
• For severe AWS (CIWA-Ar ≥15): Consider loading dose followed by symptom-triggered dosing
• Reassess CIWA-Ar score every 4-6 hours and administer additional doses for scores >8

Supportive Care (Essential Components)

• Thiamine: 100-300 mg IV/IM daily (administer before glucose to prevent Wernicke's encephalopathy)
• Fluids: IV hydration to correct dehydration
• Electrolytes: Correct deficiencies, especially magnesium
• Glucose: Monitor and supplement as needed
• Quiet, comfortable environment with minimal stimulation

Monitoring During Treatment

• Assess sedation level using Richmond Agitation Sedation Scale (target 0 to -1)
• Monitor respiratory rate, blood pressure, and heart rate every 1-2 hours initially
• Reassess CIWA-Ar score every 4-6 hours
• Monitor for phenobarbital toxicity: excessive sedation, respiratory depression, hypotension
• Consider phenobarbital serum levels in patients with altered mental status

Special Considerations

• Liver dysfunction: Phenobarbital may be safer than long-acting benzodiazepines but still requires careful monitoring
• Respiratory concerns: Use with caution in patients with respiratory insufficiency
• Psychiatric consultation: Recommended for evaluation and long-term abstinence planning 1
• Refractory cases: Consider adjunctive medications (dexmedetomidine, propofol) for ICU patients with severe, refractory withdrawal 3

Advantages of Phenobarbital Protocol

• Longer half-life (79-96 hours) reduces risk of breakthrough symptoms
• Anti-glutamate activity addresses a different pathway than benzodiazepines
• Lower rates of delirium compared to benzodiazepines (0% vs 8.6%) 2
• May require fewer adjunctive medications
• Potentially lower risk of respiratory depression compared to equivalent doses of benzodiazepines

Discharge Planning

• Continue thiamine supplementation for 2-3 months 1
• Arrange psychiatric follow-up for alcohol use disorder treatment
• Do not continue phenobarbital as an outpatient medication for alcohol abstinence
• Consider baclofen or acamprosate for maintenance of abstinence 1

Cautions and Pitfalls

• Avoid using phenobarbital concurrently with high doses of benzodiazepines due to risk of respiratory depression
• Do not use antipsychotics as standalone treatment for AWS as they may lower seizure threshold 4
• Phenobarbital should be administered by experienced clinicians with appropriate monitoring capabilities
• Always consider other etiologies (trauma, infection, metabolic disorders) when evaluating new-onset seizures

Recent evidence suggests that phenobarbital protocols may result in lower rates of delirium and similar or better outcomes compared to benzodiazepine protocols, particularly in patients with severe AWS or those not responding to standard benzodiazepine treatment 2, 5.