Management of Alcohol Withdrawal in Patients with Concurrent Hepatic Encephalopathy
Lorazepam is the preferred benzodiazepine for managing alcohol withdrawal in patients with concurrent hepatic encephalopathy due to its pharmacokinetic profile, which includes no active metabolites and relatively preserved elimination through glucuronidation in liver disease. 1
Assessment and Initial Management
Use the CIWA-Ar score to assess withdrawal severity:
- Mild (≤7): Monitor, may not require medication
- Moderate (8-14): Initiate benzodiazepine treatment
- Severe (≥15): Aggressive benzodiazepine treatment, consider inpatient management 1
Before administering benzodiazepines:
- Assess for signs of hepatic encephalopathy (confusion, asterixis, altered consciousness)
- Check liver function tests and coagulation profile
- Calculate MELD score to determine severity of liver disease
Pharmacological Management
Benzodiazepine Selection and Dosing
Lorazepam is preferred over other benzodiazepines in patients with cirrhosis due to:
- No active metabolites
- Preserved elimination through glucuronidation in liver disease
- Shorter half-life allowing easier dose titration 1
Initial dosing of lorazepam:
- Start with 1-2 mg orally every 4-6 hours as needed
- Maximum daily dose should not exceed 8 mg in cirrhotic patients
- Assess CIWA-Ar score before each dose to guide treatment 1
Avoid diazepam despite its advantages in non-cirrhotic patients (rapid onset, long half-life) as it can accumulate in patients with liver disease, potentially worsening hepatic encephalopathy 2, 3
Supportive Medications
Thiamine supplementation:
- Administer 100-300 mg/day for 4-12 weeks to prevent Wernicke's encephalopathy 1
- Always give thiamine before glucose administration
Nutritional support:
- Provide adequate protein (1.2-1.5 g/kg/day) and calories (35-40 kcal/kg/day) once stabilized
- Consider enteral nutrition if oral intake is inadequate 1
Fluid and Electrolyte Management
Aggressive fluid resuscitation with intravenous fluids:
- Normal saline as initial fluid
- Follow with mixture of saline and 5% glucose solution 1
Electrolyte replacement:
- Replace potassium, phosphorus, and magnesium based on laboratory values
- Monitor electrolytes frequently during treatment 1
Special Considerations for Hepatic Encephalopathy
Identify and treat precipitating factors of hepatic encephalopathy:
Lactulose administration:
- Initial dose: 25 mL every 1-2 hours until bowel movement
- Maintenance: 15-30 mL 2-4 times daily to achieve 2-3 soft bowel movements per day
Rifaximin:
- Consider adding rifaximin 550 mg twice daily in patients with recurrent hepatic encephalopathy
Long-term Management
Pharmacotherapy for alcohol use disorder:
- Baclofen (30-60 mg/day) is the safest option in liver disease
- Acamprosate (666 mg three times daily) is also safe in liver disease
- Gabapentin (600-1,800 mg/day) can be used for moderate alcohol use disorder
- Avoid disulfiram in patients with liver disease 1
Psychosocial interventions:
- Brief interventions using the FRAMES model
- Cognitive-behavioral therapy
- Motivational interviewing 1
Monitoring and Follow-up
Monitor for:
- Excessive sedation, respiratory depression, and confusion
- Worsening of hepatic encephalopathy
- Signs of infection or gastrointestinal bleeding
- Electrolyte abnormalities
Regular follow-up:
- Continue medications for alcohol use disorder for 3-12 months
- Provide ongoing psychosocial support 1
Important Caveats
The management of alcohol withdrawal in patients with hepatic encephalopathy presents a therapeutic dilemma due to the antagonistic nature of the conditions:
- Hepatic encephalopathy involves GABAergic delirium (excess GABA activity)
- Alcohol withdrawal involves glutamatergic-noradrenergic delirium (reduced GABA activity) 3
Benzodiazepines can worsen hepatic encephalopathy, but are necessary to treat alcohol withdrawal
Avoid carbamazepine and divalproex despite their efficacy in alcohol withdrawal due to their potential hepatotoxicity 4