What is the treatment for hepatic encephalopathy?

Treatment of Hepatic Encephalopathy

Lactulose is the first-line treatment for hepatic encephalopathy, with rifaximin as an effective add-on therapy for prevention of recurrence when lactulose alone is insufficient. 1, 2

First-Line Treatment

Lactulose Therapy

• Initial dosing: 30-45 mL every 1-2 hours until 2 bowel movements occur
• Maintenance dosing: 25-30 mL (20-30 g) orally every 12 hours
• Target: 2-3 soft stools per day 2, 3
• Mechanism: Acidifies the gastrointestinal tract, trapping ammonia as NH4+ in the colon and reducing plasma ammonia concentrations 4
• Efficacy: Reduces blood ammonia levels by 25-50%, which generally parallels improvement in mental state 3

Administration Routes

• Oral: Preferred route when possible
• Nasogastric tube: For patients unable to take oral medications
• Rectal (enema): 200g lactulose enema for patients with severe HE when oral intake is inappropriate 2

Add-on Therapy

Rifaximin

• Dosage: 550 mg orally twice daily 2, 5
• Indication: Add-on to lactulose when lactulose alone is insufficient, especially for prevention of recurrent episodes 2
• Efficacy: Reduces risk of recurrent HE by 58% compared to placebo when added to lactulose 2
• Mechanism: Decreases intestinal production and absorption of ammonia by altering gastrointestinal flora 6

Management Algorithm

1. Identify and treat precipitating factors (GRADE II-2, A, 1) 1:

   • Gastrointestinal bleeding
   • Infection
   • Constipation
   • Excessive protein intake
   • Dehydration
   • Renal dysfunction
   • Electrolyte imbalances
   • Psychoactive medications
   • Acute hepatic injury

2. Initiate lactulose (GRADE II-1, B, 1) 1

3. For recurrent episodes or inadequate response to lactulose:

   • Add rifaximin 550 mg twice daily (GRADE I, A, 1) 1, 2

4. For severe HE (Grade III-IV):

   • Admit to ICU immediately
   • Secure airway if Glasgow Coma Scale <7
   • Position head elevated at 30 degrees
   • Consider continuous kidney replacement therapy for rapidly deteriorating neurological status with ammonia levels >150 μmol/L 2

5. Alternative therapies (if standard therapy fails):

   • Oral branched-chain amino acids (BCAAs) (GRADE I, B, 2) 1
   • IV L-ornithine L-aspartate (LOLA) (GRADE I, B, 2) 1
   • Neomycin (limited by ototoxicity and nephrotoxicity) (GRADE II-1, B, 2) 1
   • Metronidazole (limited by neurotoxicity concerns) (GRADE II-3, B, 2) 1
   • Polyethylene glycol (PEG) with lactulose (may improve outcomes compared to lactulose alone) 7
   • Albumin 1.5 g/kg/day until clinical improvement or for maximum of 10 days 2

Nutritional Support

• Daily energy intake: 35-40 kcal/kg
• Protein intake: 1.2-1.5 g/kg (avoid long-term protein restriction)
• Meal frequency: 4-6 small meals per day including night snack 2

Monitoring and Follow-up

• Perform frequent neurological evaluations to monitor improvement in mental status
• Ensure adequate bowel movements (2-3 per day)
• Monitor for adverse effects of medications
• Provide patient and caregiver education about medication adherence and recognition of early signs of recurrence 2

Special Considerations

• TIPS procedure: May worsen hepatic encephalopathy; careful case selection is important 1
• Liver transplantation: Consider for patients with severe HE unresponsive to medical treatment 2
• Prophylaxis: Lactulose is recommended for prevention of recurrent episodes after the initial episode (GRADE II-1, A, 1) 2

Caveats and Pitfalls

• Long-term use of neomycin can cause ototoxicity, nephrotoxicity, and neurotoxicity 1
• Rifaximin has not been extensively studied in patients with MELD scores >25 5
• Excessive lactulose can cause diarrhea, dehydration, and electrolyte imbalances, which can worsen HE
• Protein restriction is no longer recommended long-term and may worsen nutritional status 2
• Patients with grade III-IV HE are at high risk for aspiration and require close monitoring 2