What is the recommended management for hepatic encephalopathy?

Management of Hepatic Encephalopathy

Initiate lactulose 25 mL orally every 12 hours immediately as first-line therapy while simultaneously identifying and correcting precipitating factors, which alone resolves approximately 90% of cases. 1, 2

Immediate Assessment and Triage

Determine the grade of encephalopathy to guide admission decisions:

• Grades 0-2: Manage on general medicine ward with frequent mental status monitoring 1, 3
• Grades 3-4: Immediate ICU admission is mandatory due to inability to protect airway and high aspiration risk 1

Identify and correct precipitating factors (resolves ~90% of cases): 1, 2, 3

• Infections (most common)
• Gastrointestinal bleeding
• Constipation
• Dehydration and electrolyte disturbances
• Sedative medications (benzodiazepines, opioids)
• Renal failure
• Hypokalemia

Exclude alternative causes of altered mental status: 1, 2

• Consider brain CT imaging to rule out intracranial hemorrhage, especially with focal deficits
• Measure plasma ammonia (normal level should prompt diagnostic reconsideration, but do not rely exclusively on ammonia for diagnosis or monitoring) 1, 3

First-Line Pharmacological Treatment

Lactulose is the cornerstone of therapy: 1, 2, 4

• Dosing: 25 mL orally every 12 hours, titrated to achieve 2-3 soft bowel movements per day 1, 2
• Alternative routes: Administer via nasogastric tube in patients unable to swallow or at aspiration risk 1
• Mechanism: Acidifies colonic pH, traps ammonia as non-absorbable NH4+, and increases bacterial nitrogen incorporation 5, 6
• Efficacy: Reduces blood ammonia by 25-50% with clinical response in approximately 75% of patients 4

Common pitfall: Avoid excessive lactulose causing diarrhea, dehydration, hypernatremia, or perianal irritation 2

Second-Line and Adjunctive Therapy

Rifaximin 550 mg orally twice daily should be added in specific circumstances: 1, 7

• After recurrent episodes: Add rifaximin after more than one additional episode of overt hepatic encephalopathy within 6 months despite lactulose therapy 1, 2
• Efficacy: Reduces recurrence risk by 58%, improves quality of life, and reduces hospital readmissions 1, 2
• Safety: Can be used for >24 months with good safety profile 2
• Important: Do NOT use rifaximin as monotherapy for initial treatment of overt hepatic encephalopathy 2

Note: In clinical trials, 91% of patients receiving rifaximin were using lactulose concomitantly 7

Secondary Prophylaxis Strategy

After the first episode of overt hepatic encephalopathy: 1, 2, 3

1. Continue lactulose indefinitely as secondary prophylaxis
2. Add rifaximin 550 mg twice daily after recurrent episodes despite adequate lactulose therapy
3. Refer to transplant center for liver transplantation evaluation, as transplant is the definitive treatment 1, 3

Discontinuation considerations: Prophylactic therapy may be discontinued only when precipitating factors are well-controlled, infections treated, variceal bleeding resolved, or liver function/nutritional status significantly improved 8

Nutritional Management

Address malnutrition present in ~75% of patients with hepatic encephalopathy: 8

• Avoid chronic protein restriction (detrimental and increases risk of sarcopenia)
• Provide moderate hyperalimentation with small, frequent meals throughout the day
• Include late-night snack to avoid prolonged fasting 8
• Assess nutritional status by dietary history, anthropometric measurements, and muscle strength evaluation
• Multivitamin supplementation is generally recommended 8

Medications to Avoid

Strictly avoid the following in patients with hepatic encephalopathy: 1

• Proton pump inhibitors
• Benzodiazepines
• All sedatives and psychoactive drugs
• These medications worsen encephalopathy and have delayed clearance in liver failure

Special Considerations for Minimal/Covert Hepatic Encephalopathy

Routine treatment is NOT recommended for minimal or covert hepatic encephalopathy (West Haven Grade 0-I): 8

• Exceptions may be made on a case-by-case basis, particularly for patients with Grade I hepatic encephalopathy affecting quality of life or driving ability
• Consider using the animal naming test to detect covert hepatic encephalopathy 3

Monitoring and Follow-Up

For patients on general medicine ward: 3

• Perform frequent mental status checks
• Transfer to ICU if consciousness deteriorates to grade 3-4
• Monitor for metabolic abnormalities (glucose, potassium, magnesium, phosphate)

If lactulose fails to improve encephalopathy: 2

• Search for unrecognized precipitating factors
• Consider alternative causes of encephalopathy
• Ensure adequate dosing (2-3 soft stools per day)
• Add rifaximin if not already prescribed