How to manage hyperammonemia with sodium benzoate?

From the Guidelines

For an ammonia level of 94, sodium benzoate can be administered at a loading dose of 250 mg/kg intravenously over 90 min, followed by a maintenance dose as recommended in the guidelines. The management of hyperammonemia with sodium benzoate should be based on the patient's weight, with a maximum daily dose of 12 g, as high-dose benzoate can be toxic and lethal within 1 hour 1.

Key Considerations

• The dosage for patients with a weight less than 20 kg is 250 mg/kg, and for those with a weight greater than 20 kg, it is 5.5 g/m2, given over 90 min as a bolus and then as maintenance over 24 hours 1.
• Sodium benzoate works by providing an alternative pathway for nitrogen excretion, conjugating with glycine to form hippurate, which is readily excreted by the kidneys, thereby reducing ammonia levels.
• Treatment should continue until ammonia levels decrease below 50-60 μmol/L, with frequent monitoring of ammonia levels every 4-6 hours initially.
• Potential side effects include nausea, vomiting, and metabolic acidosis, which should be monitored.

Comprehensive Approach

• This treatment should be part of a comprehensive approach including:
  • Protein restriction
  • Lactulose administration
  • Addressing the underlying cause of hyperammonemia
• The decision to initiate dialysis should be based on the evolving clinical status of the patient, rather than rigid numerical values of ammonia levels 1.
• Institutional preference, local facilities, and the safety, efficacy, and complications of each type of dialysis should influence the choice of dialysis modality 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 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 Maintenance infusions may be continued until elevated plasma ammonia levels have been normalized or the patient can tolerate oral nutrition and medications 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)].

To manage an ammonia level of 94 with sodium benzoate, 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.

• Key components of treatment include:
  • Arginine supplementation
  • Caloric supplementation
  • Dietary protein restriction
  • Hemodialysis (if necessary)
• Monitoring of plasma ammonia levels, as well as other clinical laboratory values and clinical responses, is crucial to assess patient response to treatment 2.
• Hemodialysis may be considered if the patient has severe hyperammonemia or is not responsive to sodium phenylacetate and sodium benzoate injection administration 2.

From the Research

Managing Hyperammonemia with Sodium Benzoate

• Hyperammonemia is a serious condition that can lead to cerebral edema, encephalopathy, seizures, coma, and death 3.
• Sodium benzoate is used as an ammonia scavenger to manage hyperammonemia, particularly in cases where glutamine levels are significantly reduced 4.
• The management of hyperammonemia includes reducing ammonia production, decreasing intestinal absorption, and augmented removal of ammonia with renal replacement therapy 3.
• Sodium benzoate should be used as a first-line ammonia scavenger for symptomatic hyperammonemia instead of sodium phenylacetate or phenylbutyrate, especially when glutamine levels are low 4.

Treatment Approaches

• The treatment of hyperammonemia involves a multi-step approach, including:
  • Reducing protein intake and reversing catabolism
  • Pharmacologic treatment with ammonia scavengers such as sodium benzoate
  • Extracorporeal therapies such as hemodialysis or hemofiltration in severe cases 5, 6
• The choice of treatment depends on the severity of the condition, the presence of underlying liver disease or inborn errors of metabolism, and the patient's overall clinical status.

Pharmacotherapy for Hyperammonemia

• Sodium benzoate is a key pharmacotherapeutic agent used to manage hyperammonemia, particularly in cases where glutamine levels are low 4, 6.
• Other pharmacotherapeutic agents, such as lactulose and rifaximin, may also be used to manage hyperammonemia, particularly in the context of hepatic encephalopathy 7.