What is the treatment for hyperammonemia?

From the Guidelines

Treatment for hyperammonemia should focus on immediately reducing ammonia levels through a combination of stopping protein intake, providing intravenous glucose, and administering medications such as sodium benzoate and sodium phenylacetate, with consideration of hemodialysis or continuous renal replacement therapy for severe cases, as recommended by the most recent guidelines 1.

Initial Management

Initial management includes:

• Stopping protein intake to reduce ammonia production
• Providing adequate calories through intravenous glucose at a rate of 8–10 mg/kg/min to prevent catabolism
• Correcting electrolyte imbalances
• Administering i.v. lipids at 0.5 g/kg daily, up to 3 g/kg daily
• Ensuring caloric intake of ≥100 kcal/kg daily

Medications

Medications are essential in the treatment of hyperammonemia, including:

• Sodium benzoate and sodium phenylacetate (combined as Ammonul) as first-line treatments to create alternative pathways for nitrogen excretion
• L-arginine or L-citrulline supplementation to help urea cycle disorders by enhancing ammonia removal
• L-carnitine supplementation, especially in patients with organic acidaemias
• Vitamins such as B12 and biotin

Severe Cases

For severe cases of hyperammonemia, especially those with rapidly deteriorating neurological status, coma, or cerebral edema, hemodialysis or continuous renal replacement therapy (CKRT) should be considered promptly, with CKRT being the recommended first-line treatment when possible, as it allows for rapid clearance of ammonia and reduces the need for switching between HD and CKRT modalities 1.

Supportive Care

Supportive care is crucial and includes:

• Managing cerebral edema with mannitol or hypertonic saline
• Controlling seizures with anticonvulsants
• Preventing catabolism through adequate nutrition
• Monitoring and managing potential complications of treatment, such as hypotension and electrolyte imbalances.

From the FDA Drug Label

Sodium Phenylacetate and Sodium Benzoate Injection is indicated as adjunctive therapy in pediatric and adult patients for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle During acute hyperammonemic episodes, arginine supplementation, caloric supplementation, dietary protein restriction, hemodialysis, and other ammonia lowering therapies should be considered Sodium Phenylacetate and Sodium Benzoate Injection should be administered as a loading dose infusion over 90 to 120 minutes, followed by the same dose repeated as a maintenance infusion administered over 24 hours Treatment of hyperammonemia also requires caloric supplementation and restriction of dietary protein. Non-protein calories should be supplied principally as glucose (8 to 10 mg/kg/min) with an intravenous fat emulsion added Hemodialysis should be considered in patients with severe hyperammonemia or who are not responsive to Sodium Phenylacetate and Sodium Benzoate Injection administration

The treatment for hyperammonemia includes:

• Sodium Phenylacetate and Sodium Benzoate Injection as adjunctive therapy
• Arginine supplementation
• Caloric supplementation
• Dietary protein restriction
• Hemodialysis in severe cases or non-responsive patients
• Other ammonia lowering therapies as needed Maintenance infusions of Sodium Phenylacetate and Sodium Benzoate Injection may be continued until elevated plasma ammonia levels have been normalized or the patient can tolerate oral nutrition and medications 2.

From the Research

Treatment Options for Hyperammonemia

The treatment of hyperammonemia largely depends on the underlying cause, but the primary goal is to reduce ammonia levels and prevent further neurological damage. Some key treatment options include:

• Establishing anabolism to avoid endogenous protein breakdown and amino acid imbalances 3
• Pharmacological treatment options to improve urea cycle function or remove nitrogen, such as intravenous sodium benzoate 4
• Renal replacement therapy to remove excess ammonia from the blood 5
• Low-protein diet, balanced and supplemented to avoid deficiencies of essential amino acids, trace elements, or vitamins 6
• Use of nitrogen scavengers, such as sodium phenylacetate + sodium benzoate 4, 6

Management of Acute Hyperammonemia

In cases of acute hyperammonemia, immediate treatment is crucial to prevent severe brain damage or death. Treatment may involve:

• Extracorporeal means, such as haemodialysis, to detoxify ammonia 6
• Intravenous drugs that work as nitrogen scavengers 6
• Protective measures to prevent life-threatening neurological injury 5

Treatment of Hyperammonemia in Liver Failure

In patients with liver failure, treatment of hyperammonemia focuses on reducing ammonia levels and alleviating symptoms of hepatic encephalopathy. Treatment options may include:

• Lactulose, probiotics, and rifaximin to reduce ammonia production or absorption 7
• Closure of large portosystemic shunts to reduce ammonia levels 7
• Targeting inflammation to make the brain less susceptible to the deleterious effects of ammonia 7