Hyperammonemia Treatment & Management

Updated: Nov 09, 2018
  • Author: Jasvinder Chawla, MD, MBA; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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Treatment

Medical Care

The aims are to correct biochemical abnormalities and ensure adequate nutritional intake. Treatment involves compounds that increase the removal of nitrogen waste. These compounds convert nitrogen into products other than urea, which are then excreted; hence, the load on the urea cycle is reduced. The first compounds to be used were sodium benzoate and arginine. Later, phenylacetate was used, which has now been replaced by phenylbutyrate.

  • Treatment of neonatal hyperammonemic coma

    • Protein intake should be stopped.

    • Calories should be supplied by giving hypertonic 10% glucose.

    • Hemodialysis should be started promptly in all comatose neonates with plasma ammonium levels greater than 10 times reference range. Plasma ammonium levels are reduced quickly and the total dialysis time is shorter with hemodialysis than with peritoneal dialysis. Continuous arteriovenous or venovenous hemofiltration may be used as an alternative method. [27]

    • Intravenous sodium benzoate and phenylacetate should be started once the plasma ammonium level falls to 3-4 times the upper limit of the reference range.

    • Intravenous arginine should be provided.

    • Corticosteroids are not indicated for the management of increased intracranial pressure in hyperammonemia because they induce negative nitrogen balance. Mannitol is not effective in treating cerebral edema induced by hyperammonemia.

    • Valproic acid should not be used to treat seizures as it decreases urea cycle function and increases serum ammonia levels.

  • Treatment of intercurrent hyperammonemia

    • Patients with urea cycle defects may present with episodes of hyperammonemia secondary to increased protein intake, increased catabolism, or noncompliance with therapy. This should be recognized early and treated as an emergency.

    • Treatment should be started if the plasma ammonium level is 3 times the reference level.

    • All nitrogen intake should be stopped.

    • High parenteral intake of calories from 10-15% glucose and intralipids should be provided.

    • Intravenous infusion of sodium benzoate and phenylacetate should be started.

    • Plasma ammonium levels should be checked at the end of the infusion and every 8 hours.

    • Once the ammonia level is near normal, oral medication should be started.

    • If the level does not decrease in 8 hours, hemodialysis should be started.

    • Osmotic demyelination syndrome has been reported as a potential serious complication of standard therapy for hyperammonemia in patients with ornithine transcarbamylase deficiency. [28]

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Surgical Care

See the list below:

  • Liver transplantation: The main goal of liver transplantation is to correct the metabolic error. In one recent study of liver transplantation in patients with defects causing hyperammonemia, metabolic errors were corrected in all patients, and requirements for medication and dietary restriction were eliminated. Neurologic outcomes correlated closely with status prior to transplantation. Thus, liver transplantation is a good option for patients with urea cycle defects who have not suffered major brain injury.

  • Liver cell transplantation, administered as multiple intraportal infusions of cryopreserved hepatocytes, has been reported as a potentially less invasive alternative or bridging to liver transplantation. [2, 3]

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Consultations

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  • Nephrologist for hemodialysis

  • Dietitian to help with the dietary management and education of the family

  • Geneticist for possible testing of family members and to provide genetic counseling

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Diet

Dietary management consists of the following:

  • Low protein intake: Current recommendation is 0.7 g/kg/day of protein and 0.7 g/kg/day of essential amino acid mixture. During the first 6 months, an infant may tolerate 1.5-2 g/kg/day of protein.

  • Arginine supplementation: Arginine is an essential amino acid in patients with urea cycle defects. In neonates and in OTC and CPSI deficiencies, citrulline can be given as a source of arginine as it gives one less nitrogen atom; in late-onset cases, however, arginine is acceptable because of increased nitrogen tolerance. Citrulline levels are elevated in ASS and ASL deficiencies and citrulline should not be administered in patients with unknown enzyme deficiency.

  • Providing enough calories to meet energy requirements

  • A tube feeding may be needed to provide a stable feeding route. A gastrostomy tube is the most reliable way to administer medications and fluids during illness and helps provide adequate nutritional support to prevent catabolism. [1]

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Activity

Restricting physical activity of these children is not necessary; however, caloric intake should be sufficient to avoid protein breakdown.

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