What is the recommended management of hyperammonemia in a patient with cirrhosis?

Management of Elevated Ammonia in Cirrhosis

The primary management of hyperammonemia in cirrhosis focuses on treating hepatic encephalopathy (HE) empirically with lactulose or polyethylene glycol while identifying and addressing precipitating factors—routine ammonia testing is not recommended for diagnosis or to guide treatment decisions. 1

Key Principle: Ammonia Levels Should Not Guide Management

• Routine ammonia level testing in patients with cirrhosis and altered mental status is not recommended by the 2024 AASLD guidelines 1
• Ammonia levels are variable within patients and laboratories, and may be elevated in non-HE conditions 1
• Clinical studies demonstrate that lactulose dosing is not influenced by ammonia levels in practice, with no correlation between ammonia values and treatment intensity 2
• However, a normal ammonia level in a patient with coma or confusion should prompt investigation of alternative etiologies beyond HE 1

Immediate Treatment Algorithm

Step 1: Identify and Treat Precipitating Factors

The most critical initial step is identifying precipitating factors, which are present in approximately 50% of cases and lead to symptom improvement in ~90% when corrected 1:

• Gastrointestinal bleeding: Perform endoscopy, check complete blood count, digital rectal examination 1
• Infections: Start empiric antibiotics early in high-risk patients; obtain blood cultures, urinalysis with culture, chest X-ray, and consider diagnostic paracentesis 1
• Electrolyte disorders: Monitor and correct hyponatremia (maintain >130 mmol/L, ideally >135 mmol/L), hypokalemia, and acute kidney injury 1
• Dehydration: Assess volume status and correct appropriately 1
• Constipation: Ensure regular bowel movements 1
• Medications: Discontinue benzodiazepines (contraindicated in decompensated cirrhosis), limit proton pump inhibitors to strict indications, and review all CNS depressants 1

Step 2: Initiate Empiric HE Treatment

Start lactulose immediately if no obvious alternative cause is apparent, without waiting for ammonia results 1:

• Oral lactulose: 30-45 mL every 1-2 hours until achieving 2 bowel movements, then titrate to maintain 2-3 soft stools daily 1, 3
• Lactulose enema: For Grade 3-4 HE or when oral intake is inappropriate, use 300 mL lactulose in 700 mL water (total 1 L), retained for at least 30 minutes, administered 3-4 times daily 1, 3
• Polyethylene glycol: Consider as an alternative to lactulose, particularly in patients at risk of ileus or abdominal distention (4 liters over 4 hours) 1, 3

Step 3: Special Considerations for Ileus

If ileus is present with air-fluid levels on imaging, oral lactulose must be held 1, 3:

• Polyethylene glycol is the preferred alternative when patients are at risk of ileus/abdominal distention 1, 3
• Lactulose enema can be used if PEG is unavailable 1, 3
• Oral lactulose may worsen abdominal distention and carries aspiration risk in this setting 3

Step 4: Monitor and Adjust

• Goal: 2-3 soft bowel movements daily once mental status improves 1
• Monitor closely: Electrolytes (particularly sodium and potassium), renal function, volume status, and mental status to prevent dehydration and hypernatremia 1, 3
• Avoid over-treatment: Excessive lactulose can cause dehydration, hypernatremia, and severe perianal irritation 3

Additional Therapeutic Options

Rifaximin

• Add rifaximin 550 mg twice daily for patients with recurrent HE or as add-on therapy to lactulose 1, 3
• The role in acute ACLF/critically ill patients requires further investigation 1

Adjunctive Therapies (Consider in Select Cases)

• Oral branched-chain amino acids (BCAAs): May be beneficial as ancillary therapy for overt HE 1
• Intravenous L-ornithine L-aspartate (LOLA): Can be used additionally 1
• Intravenous albumin: Consider 1.5 g/kg/day in combination with lactulose for Grade ≥2 HE 1

Critical Care Considerations

Severe HE (Grade 3-4)

• Consider ICU admission for patients with Grade 3-4 HE or Glasgow Coma Scale <8 1
• Use short-acting sedatives (propofol, dexmedetomidine) if intubation and mechanical ventilation are required 1
• Insert nasogastric tube for lactulose administration if needed, with caution if recent variceal band ligation 1

Refractory Cases

• Hemodialysis should be considered in patients with severe hyperammonemia or those not responsive to medical management 1
• High ammonia levels can be reduced quickly when ammonia-scavenging therapy is combined with hemodialysis 1
• Liver transplantation is indicated for patients with severe HE who do not respond to medical treatments 1

Common Pitfalls to Avoid

• Do not delay empiric HE treatment while waiting for ammonia results or other diagnostic workup 1
• Do not use ammonia levels to guide lactulose dosing—clinical response (mental status, bowel movements) should guide therapy 1, 2
• Do not administer oral lactulose in the setting of ileus—this is explicitly contraindicated 1, 3
• Do not restrict protein intake except perhaps for very short periods in severe overt HE with GI bleeding; patients with HE tolerate normal protein diets (1.0-1.5 g/kg/day) 1
• Do not perform routine brain imaging in patients with presentations similar to prior HE episodes 1
• Do consider brain imaging for first episode of altered mental status, seizures, new focal neurological signs, or unsatisfactory response to therapy 1

Prevention Strategies

• Monitor sodium levels closely in decompensated cirrhosis, maintaining >130 mmol/L (ideally >135 mmol/L) 1
• Limit PPI use to strict validated indications due to increased HE risk from dysbiosis 1
• Contraindicate benzodiazepines in decompensated cirrhosis 1
• Secondary prophylaxis: Start long-term lactulose or rifaximin after first episode of overt HE, as 50-70% will experience recurrence within 1 year 1
• Nutritional intervention: Provide 30-35 kcal/kg/day with 1.0-1.5 g vegetable protein/kg/day, including late evening snack to avoid prolonged fasting 1