Management of Hepatic Encephalopathy in Alcoholic Liver Disease
The first-line treatment for hepatic encephalopathy (HE) in alcoholic liver disease is lactulose, with rifaximin added when lactulose alone fails to prevent recurrence. 1, 2
Four-Pronged Approach to Management
1. Initial Assessment and Stabilization
- Patients with higher grades of HE who cannot protect their airway need intensive monitoring in an ICU setting 1, 3, 4
- Position patients with head elevated at 30 degrees to reduce intracranial pressure 3
- Avoid sedatives when possible as they have delayed clearance in liver failure and interfere with neurological assessment 3, 4
2. Identify and Treat Precipitating Factors
- Controlling precipitating factors is paramount, as nearly 90% of patients can be treated with just correction of the precipitating factor 1, 2
- Common precipitating factors include:
- Alternative causes of encephalopathy should be sought and treated, as they are not infrequent in patients with advanced cirrhosis 1, 4
3. Specific Pharmacological Treatment
First-Line: Lactulose
- Start lactulose as initial treatment for overt HE 1, 2, 5
- Dosing: 25 ml orally every 12 hours, titrated to achieve 2-3 soft stools per day 2, 4
- For patients unable to take oral medications:
- Lactulose works by acidifying the gastrointestinal tract, inhibiting ammonia production by coliform bacteria 6
- Lactulose has demonstrated benefits in resolving overt HE, reducing mortality, and reducing risk of adverse effects 2
Second-Line: Rifaximin
- Add rifaximin 550 mg twice daily or 400 mg three times daily when lactulose alone fails to prevent recurrence 3, 2, 7
- Rifaximin reduces the risk of HE recurrence by 58% when added to lactulose 2, 7
- Long-term therapy with rifaximin (>24 months) has shown good safety profile for prevention of recurrence 2
- Rifaximin also reduces the risk of HE-related hospitalizations by 50% 7
4. Management of Complications and Follow-up
- Monitor for overuse of lactulose which can paradoxically precipitate HE and cause complications like dehydration, hypernatremia, and perianal irritation 2
- Educate patients and caregivers about medication effects, importance of adherence, and early signs of recurring HE 3, 4
- Consider liver transplantation for patients with recurrent intractable HE and liver failure 1, 2
Special Considerations
Diagnostic Approach
- HE is a diagnosis of exclusion; alternative causes of altered mental status should be investigated 4, 8
- Routine ammonia level testing is not recommended for diagnosis or monitoring of HE 4
- However, a normal ammonia level should prompt reevaluation of the diagnosis 2, 9
Management of Violent or Agitated Patients
- For uncontrolled agitation, use minimal doses of benzodiazepines if absolutely necessary 3
- Phenytoin is recommended if seizures are present 3
- Propofol is preferred for sedation in intubated patients due to its short half-life 4
- Dexmedetomidine can reduce ventilation duration and preserve cognitive function 4
Pitfalls to Avoid
- Delaying treatment while awaiting diagnostic confirmation can worsen outcomes 3
- Overuse of lactulose can cause complications including aspiration, dehydration, and hypernatremia 2
- Failure to identify precipitating factors may lead to poor treatment response 3
- Long-term use of antibiotics like neomycin and metronidazole should be avoided due to risks of ototoxicity, nephrotoxicity, and neurotoxicity 3
- Do not use rifaximin as monotherapy for initial treatment of overt HE 2
Monitoring and Prevention
- Secondary prophylaxis after an episode of overt HE is recommended 1
- Primary prophylaxis is not required except in patients with cirrhosis at high risk for developing HE 1
- Lactulose use is associated with higher mortality (adjusted hazard ratio 1.61), likely reflecting the severity of underlying liver disease 10