What is the management of hyperammonemia?

From the Guidelines

Management of hyperammonemia requires prompt intervention with stopping protein intake, providing adequate calories through glucose infusion, and removing excess ammonia, as well as the use of medications such as intravenous L-arginine or sodium phenylacetate/sodium benzoate, and consideration of hemodialysis or continuous renal replacement therapy for severe cases. The initial treatment should focus on stopping protein intake and providing adequate calories through glucose infusion, with a rate of 8-10 mg/kg/min 1. Additionally, intravenous lipids should be administered at a dose of 0.5 g/kg daily, up to 3 g/kg daily, and caloric intake should be at least 100 kcal/kg daily 1. Medications such as intravenous sodium benzoate, sodium phenylacetate, and L-arginine hydrochloride should be used to convert ammonia to excretable compounds, with dosing based on weight and specific deficiencies 1.

For severe cases, hemodialysis or continuous renal replacement therapy (CKRT) may be necessary, with CKRT being the recommended first-line treatment when possible 1. The decision to initiate CKRT should be based on the patient's clinical status, with consideration of factors such as rapidly deteriorating neurological status, coma, or cerebral edema, and blood ammonia levels greater than 150 μmol/L 1. Hybrid therapy, combining HD or CKRT with extracorporeal membrane oxygenation (ECMO) or therapeutic hypothermia, may also be considered in certain situations, such as haemodynamic instability or rapidly deteriorating neurological status 1.

Frequent monitoring of ammonia levels, electrolytes, and neurological status is crucial to guide therapy adjustments, and addressing underlying causes, such as hepatic dysfunction or urea cycle disorders, is essential for effective management 1. Long-term management includes protein restriction, branched-chain amino acid supplementation, and prevention of precipitating factors like GI bleeding, infection, or dehydration 1.

The use of lactulose and rifaximin, as mentioned in the example answer, may not be directly supported by the provided evidence, and therefore, their use should be considered on a case-by-case basis. The most recent and highest quality study, 1, provides the most relevant guidance for the management of hyperammonemia, and its recommendations should be prioritized in clinical practice.

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 management of hyperammonemia includes:

• Starting Sodium Phenylacetate and Sodium Benzoate Injection as soon as the diagnosis is made
• Caloric supplementation with non-protein calories, mainly glucose, and intravenous fat emulsion
• Restriction of dietary protein
• Maintaining a caloric intake of more than 80 kcal/kg/day
• Considering hemodialysis in patients with severe hyperammonemia or those not responsive to Sodium Phenylacetate and Sodium Benzoate Injection 2, 2, 2

From the Research

Management of Hyperammonemia

The management of hyperammonemia involves a combination of pharmacological and non-pharmacological interventions. The primary goal is to reduce plasma ammonium levels and prevent further neurological damage.

• Pharmacological treatment:
  • Sodium phenylacetate and sodium benzoate have been shown to lower plasma ammonium levels and improve survival in patients with urea-cycle disorders 3, 4, 5.
  • L-arginine is also used in the treatment of hyperammonemia, particularly in patients with argininosuccinic acid synthetase deficiency 5.
• Non-pharmacological treatment:
  • Hemodialysis may be necessary to control hyperammonemia, especially in neonates and older patients who do not respond to pharmacological treatment 3, 4, 6.
  • Provision of adequate calories to prevent catabolism and promote anabolism is crucial in the management of hyperammonemia 3, 7.
  • Therapeutic hypothermia and barbiturate-induced coma may be used to manage cerebral edema associated with hyperammonemia 4.
• Supportive care:
  • Prompt recognition and treatment of hyperammonemia are critical to prevent long-term neurological damage and improve outcomes 3, 4, 7.
  • Monitoring of plasma ammonium levels, electrolytes, and acid-base balance is essential to guide treatment and prevent complications 3, 4, 7.
• Safety considerations:
  • Appropriate dosing of sodium benzoate and sodium phenylacetate is crucial to avoid toxicity, which can be severe and life-threatening 6.
  • Close monitoring of patients receiving these medications is necessary to prevent and promptly manage any adverse effects 6.