How to manage hyperammonemia (elevated ammonia level)?

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Last updated: April 24, 2025View editorial policy

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From the Guidelines

An ammonia level of 94 is significantly elevated and requires immediate medical attention, and the management should focus on lowering ammonia levels while addressing the underlying cause, typically liver dysfunction or urea cycle disorders, with the primary goal of preventing morbidity, mortality, and improving quality of life. The management of hyperammonemia should prioritize the use of nitrogen-scavenging agents, such as sodium benzoate and sodium phenylacetate, as recommended in the consensus guidelines for management of hyperammonaemia in pediatric patients receiving continuous kidney replacement therapy 1.

  • The initial management should include:
    • Discontinuation of all oral feeds and provision of adequate calories (≥100 kcal/kg daily) as intravenous glucose and lipids, with a glucose infusion rate of 8–10 mg/kg/min and lipids (0.5 g/kg daily, up to 3 g/kg daily) 1.
    • Administration of nitrogen-scavenging agents, such as sodium benzoate and sodium phenylacetate, at the recommended dosage, with a maximum dose of 12 g daily for sodium benzoate, given over 90 min as bolus then as maintenance over 24 h 1.
    • Consideration of urea cycle intermediates, such as l-arginine or l-citrulline, as primers of the urea cycle to aid in ammonia removal, with the choice of intermediate depending on the specific deficiency 1.
  • The decision to initiate dialysis, such as continuous kidney replacement therapy (CKRT) or intermittent hemodialysis (HD), should be based on the severity of the hyperammonemia, the patient's clinical status, and the availability of dialysis equipment and staff, with CKRT being the recommended first-line treatment for hyperammonemia when possible 1.
  • The use of CKRT or HD should be guided by the consensus recommendations, with CKRT being recommended for patients with rapidly deteriorating neurological status, coma, or cerebral edema, and HD being recommended for patients who require rapid ammonia clearance 1.
  • Frequent ammonia level checks are necessary to assess treatment response, and the management should be adjusted accordingly to prevent morbidity, mortality, and improve quality of life.

From the FDA Drug Label

Lactulose causes a decrease in blood ammonia concentration and reduces the degree of portal-systemic encephalopathy. Controlled studies have shown that lactulose solution therapy reduces the blood ammonia levels by 25 to 50%; The patient with an ammonia level of 94 should be managed with lactulose (PO) as it has been shown to decrease blood ammonia concentration and reduce the degree of portal-systemic encephalopathy 2, 2.

  • The goal of treatment is to reduce the blood ammonia levels, which can be achieved with lactulose therapy.
  • Lactulose has been shown to reduce blood ammonia levels by 25 to 50% in controlled studies 2.

From the Research

Management of Hyperammonemia

To manage an ammonia level of 94, several treatment options can be considered:

  • Sodium benzoate can be used to reduce plasma ammonia levels, as it increases the urinary excretion of hippuric acid 3, 4
  • Phenylacetic acid can also control hyperammonemia and improve EEG findings 3
  • Lactulose and rifaximin are commonly used for secondary prophylaxis and are the mainstay of current therapy for hyperammonemia 5
  • Pharmacological treatment options exist to improve urea cycle function or to remove nitrogen, but their use depends on the underlying disorder 6
  • Establishing anabolism to avoid endogenous protein breakdown and amino acid imbalances is also important, especially in pediatric patients 6

Treatment Approach

The treatment approach for hyperammonemia largely depends on the underlying cause, and prompt management is crucial to prevent deleterious consequences 6, 4

  • A solid understanding of the fundamental pathophysiology, differential diagnosis, and treatment approaches available is necessary for appropriate and timely management 7
  • Increased awareness of hyperammonemia and its prompt management can improve patient outcomes 6, 4

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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