What is the recommended management for hepatic encephalopathy?

Management of Hepatic Encephalopathy

Immediate Four-Pronged Approach

All patients with hepatic encephalopathy should receive immediate treatment with lactulose as first-line therapy while simultaneously identifying and correcting precipitating factors, which alone resolves approximately 90% of cases. 1

The management follows a structured four-pronged approach 1:

• Initiate basic care for patients with altered consciousness, including airway protection assessment 1
• Exclude alternative causes of altered mental status (intracranial hemorrhage, infection, metabolic derangements, structural lesions) 1, 2
• Identify and correct precipitating factors - present in ~50% of cases and include infection, gastrointestinal bleeding, constipation, dehydration, electrolyte disturbances (especially hyponatremia <130 mmol/L), and sedative medications 1, 3
• Begin empirical lactulose therapy without delay 1

Severity-Based Triage

Grades 0-2 (Mild to Moderate)

• Manage on general medicine ward with frequent mental status monitoring 2
• Transfer to ICU if consciousness deteriorates 2

Grades 3-4 (Severe)

• Immediate ICU admission is mandatory for patients unable to protect their airway (Glasgow Coma Score <7) 1
• These patients are at high risk for aspiration and require intensive monitoring 1
• ICU admission is not contraindicated by hepatic encephalopathy alone, as it is potentially fully reversible 1

First-Line Pharmacological Treatment

Lactulose Dosing

Lactulose 25 mL orally every 12 hours, titrated to achieve 2-3 soft bowel movements per day 1, 4, 5

• Reduces blood ammonia levels by 25-50% with clinical response in approximately 75% of patients 5
• Can be administered via nasogastric tube in patients unable to swallow or at aspiration risk 1
• Mechanism: acidification of gastrointestinal tract inhibits ammonia production by coliform bacteria 6, 7
• Lactulose enemas can be used in patients unable to take oral therapy 8

Critical pitfall: Excessive lactulose dosing can cause aspiration, dehydration, hypernatremia, and severe perianal skin irritation 4

Second-Line and Adjunctive Therapy

Rifaximin

Rifaximin 550 mg orally twice daily should be added to lactulose for secondary prophylaxis after >1 additional episode of overt hepatic encephalopathy within 6 months 1, 9

• Reduces recurrence risk by 58% (from 45.9% to 22.1%, number needed to treat = 4) 1
• Decreases hospitalization risk from 22.6% to 13.6% (number needed to treat = 9) 1
• Safe for maintenance therapy beyond 24 months 4
• Should NOT be used as monotherapy for initial treatment of overt hepatic encephalopathy 4
• In the pivotal trials, 91% of patients were using lactulose concomitantly 9

Secondary Prophylaxis Strategy

After the first episode of overt hepatic encephalopathy, continue lactulose indefinitely as secondary prophylaxis 1, 4

• Lactulose reduces 14-month recurrence risk from 47% to 20% 1
• Add rifaximin after recurrent episodes despite lactulose therapy 1, 4

Diagnostic Considerations

Ammonia Levels

• Measure plasma ammonia in suspected cases - a normal ammonia level should prompt reevaluation of the diagnosis 4, 3
• However, do not rely exclusively on ammonia levels for diagnosis or monitoring 4, 2

Brain Imaging

• Perform brain CT to exclude structural lesions (hemorrhage, mass) in patients with unexplained altered mental status 2, 3
• CT has limited utility for identifying cerebral edema 2

Liver Transplantation Evaluation

The first episode of overt hepatic encephalopathy should prompt referral to a transplant center for evaluation 1, 2

• Recurrent intractable hepatic encephalopathy with liver failure is an indication for liver transplantation 1, 3
• Liver transplantation represents the definitive treatment for hepatic encephalopathy 1

Medications to Avoid

• Proton pump inhibitors increase hepatic encephalopathy risk 3
• Benzodiazepines are contraindicated in decompensated cirrhosis 3
• All sedatives should be avoided when possible due to delayed clearance in liver failure 2

Alternative Therapies (Limited Role)

Neomycin 4-12 grams daily in divided doses can be used as adjunctive therapy in chronic hepatic insufficiency when less toxic drugs fail, but nephrotoxicity, permanent ototoxicity, and neuromuscular blockade limit its use 10, 6, 7

Key Clinical Pearls

• Failure to respond to lactulose mandates searching for unrecognized precipitating factors or competing causes of encephalopathy 1, 4
• Hyponatremia <130 mmol/L is an independent risk factor requiring close monitoring and gradual correction (no more than 8-12 mEq/L per day) 3, 11
• XIFAXAN (rifaximin) has not been studied in patients with MELD scores >25, and only 8.6% of trial patients had MELD scores >19 9