How to treat hyperammonemia?

From the Guidelines

To treat hyperammonemia, immediate medical attention is necessary, and the primary goal is to reduce ammonia levels and manage symptoms.

Treatment Options

The recommended treatment includes:

• Lactulose 30-50 mL orally every hour until ammonia levels decrease, then tapered to 30-50 mL every 8-12 hours as needed 1
• Rifaximin 550 mg orally twice daily for 5-7 days, or as needed to maintain ammonia levels within a safe range 1
• In severe cases, hospitalization may be required for intravenous administration of medications such as sodium benzoate, sodium phenylacetate, or arginine 1
• Dietary modifications, including a low-protein diet, may also be recommended to reduce ammonia production in the gut 1

Additional Considerations

• Nitrogen-scavenging agents: sodium benzoate and sodium phenylacetate can be used to reduce ammonia levels, with dosages depending on body weight 1
• Urea cycle intermediates: l-arginine or l-citrulline can be supplemented to aid in ammonia removal, depending on the specific deficiency present 1
• Close monitoring: ammonia levels, liver function, and overall clinical status should be closely monitored to adjust treatment as needed 1 It is essential to work with a healthcare provider to determine the best course of treatment and to address any underlying conditions contributing to elevated ammonia levels.

From the FDA Drug Label

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. Non-protein calories should be supplied principally as glucose (8 to 10 mg/kg/min) with an intravenous fat emulsion added Attempts should be made to maintain a caloric intake of greater than 80 kcal/kg/day. 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. 1)]. 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

The treatment of hyperammonemia involves:

• Sodium Phenylacetate and Sodium Benzoate Injection: administered as a loading dose infusion over 90 to 120 minutes, followed by a maintenance infusion over 24 hours 2
• Caloric supplementation: non-protein calories supplied principally as glucose (8 to 10 mg/kg/min) with an intravenous fat emulsion added
• Restriction of dietary protein
• Hemodialysis: considered in patients with severe hyperammonemia or who are not responsive to Sodium Phenylacetate and Sodium Benzoate Injection administration 2 Key considerations:
• Monitor plasma ammonia, glutamine, quantitative plasma amino acids, blood glucose, electrolytes, venous or arterial blood gases, AST and ALT
• Monitor neurological status, Glasgow Coma Scale, tachypnea, CT or MRI scan or fundoscopic evidence of cerebral edema, and/or of gray matter and white matter damage

From the Research

Treatment Options for Hyperammonemia

• Reduction in ammonia can be achieved by targeting its production, absorption, or elimination 3
• Existing treatment options include lactulose, probiotics, rifaximin, and closure of large portosystemic shunts to lower ammonia levels and alleviate symptoms of hepatic encephalopathy 3
• Modifying the gut microbiota could be used to treat hyperammonemia, as it plays a significant role in ammonia production and absorption 4
• Intravascular resuscitation may be beneficial in cases of dehydration-associated pseudo-hyperammonemia, and may be considered as an alternative to lactulose in certain situations 5

Management Strategies

• Identification of precipitating factors and presence of cerebral edema is crucial in the management of hyperammonemia 6
• Decreasing ammonia production by reducing protein intake and reversing catabolism is an important step in managing hyperammonemia 6
• Ammonia removal can be achieved through pharmacologic treatment, and in severe cases, extracorporeal therapies may be necessary 6
• Nutritional and metabolic factors play a significant role in the cause and management of hyperammonemia, particularly in non-hepatic cases 7

Diagnostic Considerations

• Any coma of unclear cause should prompt urgent measurement of ammonia, and severe elevations warrant immediate protective measures and treatment 7
• Obtaining reliable plasma ammonia levels can be challenging due to preanalytical difficulties, and careful consideration is necessary in an acute setting 6