What are alternative methods to reduce hyperammonemia?

From the Guidelines

To lower ammonia levels, the most effective approach is to use a combination of lactulose and rifaximin, as supported by the most recent and highest quality study 1.

Key Interventions

• Medications:
  • Lactulose (15-30 ml orally 2-4 times daily) to trap ammonia in the gut and promote its excretion
  • Rifaximin (550 mg twice daily) to decrease ammonia-producing bacteria
• Dietary changes:
  • Limit protein intake to 0.8-1.2 g/kg/day, focusing on vegetable proteins rather than animal proteins
  • Stay well-hydrated
  • Avoid alcohol completely
• Lifestyle modifications:
  • Regular moderate exercise to help muscles utilize ammonia
  • Treating underlying conditions like liver disease, kidney dysfunction, or infections
  • Monitor electrolytes regularly to prevent imbalances that can worsen ammonia-related symptoms

Additional Considerations

• Branched-chain amino acids (BCAAs) may be beneficial in promoting ammonia utilization in muscle tissue, especially for patients who are intolerant to meat protein 1.
• The use of BCAAs, however, does not influence mortality, quality of life, or nutritional status, and their effects compared to non-absorbable disaccharides/antibiotics are not well established 1.
• For patients with severe hepatic encephalopathy (grade III-IV), nutrition should be provided by nasogastric tube or parenterally, as oral dietary intake may be unfeasible or impossible 1.

From the FDA Drug Label

Hemodialysis should be considered in patients with severe hyperammonemia or who are not responsive to sodium phenylacetate and sodium benzoate injection administration [ see Warnings and Precautions (5)]. In the non-neonatal study patient population treated with sodium phenylacetate and sodium benzoate injection, dialysis was required in 13% of hyperammonemic episodes Standard hemodialysis was the most frequently used dialysis method High levels of ammonia can be reduced quickly when sodium phenylacetate and sodium benzoate injection is used with hemodialysis, as the ammonia-scavenging of sodium phenylacetate and sodium benzoate injection suppresses the production of ammonia from catabolism of endogenous protein and hemodialysis eliminates the ammonia and ammonia conjugates

To lower ammonia levels, hemodialysis can be considered, especially in patients with severe hyperammonemia or those who are not responsive to sodium phenylacetate and sodium benzoate injection administration 2. Additionally, the following measures can be taken:

• Caloric supplementation
• Restriction of dietary protein
• Administration of non-protein calories, such as glucose and intravenous fat emulsion
• Monitoring of clinical laboratory values, including plasma ammonia, glutamine, and electrolytes
• Monitoring of clinical responses, including neurological status and Glasgow Coma Scale 2

From the Research

Lowering Ammonia Levels

To lower ammonia levels, several options can be considered:

• Lactulose and lactitol are commonly used for the treatment of acute and chronic hepatic encephalopathy, with the goal of achieving two to three soft bowel movements a day 3
• Rifaximin can be used as a second-line agent for patients who are unable to tolerate lactulose or lactitol, or who still have persistent chronic hepatic encephalopathy with lactulose or lactitol 3
• Combination therapy with rifaximin and lactulose may provide additional benefits in terms of increased effective rate and decreased mortality than lactulose alone in patients with hepatic encephalopathy 4
• Sodium benzoate can be used as an adjunctive agent to reduce ammonia levels, although its efficacy has not been well established and it may not be suitable for patients with significant fluid retention or kidney dysfunction 5, 6, 7
• Other options that have been investigated or are being developed include:
  • Neomycin and metronidazole as second-line agents 3
  • Nitazoxanide, the molecular adsorbent recirculating system (MARS), L-ornithine phenylacetate, and sodium phenylacetate as newer therapies with clinical promise 3
  • Zinc, ornithine aspartate, probiotics, and surgical intervention as alternative treatments 7
  • Manganese chelators, L-carnitine, N-methyl-d-aspartate receptor antagonists, and blood purification dialysis system as newer therapies still in development 7