What is the treatment for hyperammonemia?

From the Guidelines

The treatment for hyperammonemia should focus on rapidly reducing ammonia levels while addressing the underlying cause, with initial management including stopping protein intake, providing adequate calories through intravenous glucose, and correcting fluid and electrolyte imbalances, as recommended by the most recent guidelines 1.

Key Components of Treatment

• Stopping protein intake to reduce ammonia production
• Providing adequate calories through intravenous glucose to support energy needs
• Correcting fluid and electrolyte imbalances to maintain proper bodily functions
• Administering medications like sodium benzoate and sodium phenylacetate to remove ammonia by creating alternative metabolic pathways, with dosing guidelines as outlined in 1

Medications for Ammonia Removal

• Sodium benzoate and sodium phenylacetate (given as Ammonul at 250-500 mg/kg loading dose followed by maintenance infusion) or sodium phenylbutyrate (Buphenyl, 450-600 mg/kg/day orally in divided doses)
• L-arginine or L-citrulline supplementation (150-300 mg/kg/day) may be necessary for certain urea cycle disorders, as noted in 1

Reducing Intestinal Ammonia Production

• Lactulose (20-30 mL orally every 6 hours) or rifaximin (550 mg twice daily) can reduce intestinal ammonia production in liver disease, although the evidence for their use is not strong 1

Severe Cases and Long-term Management

• Hemodialysis or continuous renal replacement therapy is implemented for severe cases (ammonia levels >200-300 μmol/L) or when patients show neurological deterioration
• Long-term management includes dietary protein restriction (0.5-0.8 g/kg/day), branched-chain amino acid supplementation in liver disease, and treating precipitating factors such as infections or gastrointestinal bleeding

Importance of Prompt Treatment

• Prompt treatment is crucial as hyperammonemia can cause irreversible neurological damage through cerebral edema and neurotoxicity, highlighting the need for rapid intervention and careful management 1

From the FDA Drug Label

During acute hyperammonemic episodes, arginine supplementation, caloric supplementation, dietary protein restriction, hemodialysis, and other ammonia lowering therapies should be considered [ see Warnings and Precautions (5)]. Sodium phenylacetate and sodium benzoate injection infusion should be started as soon as the diagnosis of hyperammonemia is made. Treatment of hyperammonemia also requires caloric supplementation and restriction of dietary protein.

The treatment for hyperammonemia includes:

• Sodium phenylacetate and sodium benzoate injection
• Arginine supplementation
• Caloric supplementation
• Dietary protein restriction
• Hemodialysis 2

From the Research

Treatment Options for Hyperammonemia

The treatment for hyperammonemia, a condition characterized by elevated ammonia levels in the blood, typically targets the organs and metabolic processes involved in ammonia detoxification 3. The main treatments include:

• Lactulose and rifaximin, which have a proven role in secondary prophylaxis and are the mainstay of current therapy 3
• Sodium benzoate, an inexpensive adjunctive agent that can be used in addition to lactulose and rifaximin, particularly for patients with refractory hepatic encephalopathy who have failed to respond to standard therapies or who cannot afford them 4
• L-ornithine phenylacetate (OP), a potent ammonia scavenger being evaluated for the treatment of acute/overt hepatic encephalopathy, which has shown promise in reducing plasma ammonia levels and improving clinical outcomes 5

Considerations for Treatment

When considering treatment for hyperammonemia, it is essential to note that:

• The use of lactulose in ICU patients without chronic liver disease or significant hepatocellular injury may not be associated with improved outcomes, and its routine use in this patient population is not recommended 6
• Sodium benzoate and sodium phenylacetate can be toxic if administered in inappropriate doses, highlighting the need for careful dosing and monitoring 7
• The reduction of plasma ammonia levels is associated with improved clinical outcomes in patients with hepatic encephalopathy, making effective ammonia-lowering therapies crucial in the management of this condition 5

Key Therapies

Key therapies for hyperammonemia include:

• Lactulose: a non-absorbable disaccharide that helps reduce ammonia production in the gut 3, 6
• Rifaximin: an antibiotic that reduces ammonia production in the gut 3
• Sodium benzoate: an adjunctive agent that helps reduce ammonia levels by providing an alternative pathway for waste nitrogen disposal 4, 7
• L-ornithine phenylacetate (OP): a potent ammonia scavenger being evaluated for the treatment of acute/overt hepatic encephalopathy 5