What is the treatment for hyperammonemia?

Treatment of Hyperammonemia

The treatment of hyperammonemia requires immediate intervention with nitrogen scavengers, temporary protein restriction, intravenous glucose and lipids, and consideration of kidney replacement therapy for severe cases to prevent irreversible neurological damage. 1, 2

Initial Management

• Immediately conduct further investigations without delaying treatment when elevated ammonia levels are detected 3, 1
• Discontinue all oral feeds to reduce nitrogen load and prevent further ammonia production 3, 2
• Provide adequate calories (≥100 kcal/kg daily) as intravenous glucose and lipids to prevent catabolism 3, 1
• Maintain a glucose infusion rate of 8-10 mg/kg/min to prevent protein breakdown 3, 2
• Provide intravenous lipids starting at 0.5 g/kg daily, up to 3 g/kg daily for caloric support 3, 1
• Gradually reintroduce protein (by 0.25 g/kg daily, up to 1.5 g/kg daily) within 48 hours to prevent catabolism 3, 2

Pharmacological Therapy

Nitrogen Scavengers

• Use nitrogen-scavenging agents at recommended dosages to remove excess ammonia 3, 1:
  • Intravenous sodium benzoate (maximum dose 12 g daily):
    • Body weight <20 kg: 250 mg/kg
    • Body weight >20 kg: 5.5 g/m²
    • Given over 90 min as bolus then as maintenance over 24 hours
  • Intravenous sodium phenylacetate:
    • Body weight <20 kg: 250 mg/kg
    • Body weight >20 kg: 5.5 g/m²
    • Given over 90 min as bolus then as maintenance over 24 hours

Urea Cycle Intermediates

• Administer intravenous L-arginine hydrochloride based on specific urea cycle disorder 3, 2:
  • For OTC and CPS deficiencies:
    • Body weight <20 kg: 200 mg/kg
    • Body weight >20 kg: 4 g/m²
  • For ASS and ASL deficiencies:
    • Body weight <20 kg: 600 mg/kg
    • Body weight >20 kg: 12 g/m²
  • Given over 90 min as bolus then as maintenance over 24 hours

Additional Medications

• For organic acidemias, add L-carnitine: 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg daily 3, 1
• For hepatic encephalopathy, lactulose can be used to reduce blood ammonia levels by 25-50% by trapping ammonia in the colon 4

Kidney Replacement Therapy (KRT)

• Consider KRT when ammonia levels exceed 300-400 μmol/L despite medical therapy or with signs of moderate to severe encephalopathy 3, 2
• Intermittent hemodialysis (HD) and continuous kidney replacement therapy (CKRT) are more efficacious than peritoneal dialysis (PD) 3, 1
• Hemodialysis is the most effective method for rapidly reducing blood ammonia levels with 95-96% filtration fraction 2, 5
• CKRT, specifically high-dose CVVHD, is recommended as first-line when available 1, 2
• Use PD only when other KRT modalities are unavailable 3, 2
• Continue CKRT until ammonia levels are <200 μmol/L on at least two consecutive hourly measurements 1, 2

Monitoring During Treatment

• Check plasma ammonia levels every 3-4 hours until normalized 1, 6
• Assess neurological status regularly for signs of encephalopathy 1, 6
• Monitor electrolytes, especially during CKRT 1, 6

Common Pitfalls and Caveats

• Delayed recognition and treatment can lead to irreversible neurological damage, including seizures, coma, and death 1, 7
• Ammonia samples must be collected from free-flowing venous or arterial blood, transported on ice, and processed within 15 minutes to avoid false elevations 1, 6
• Protein restriction should not be prolonged beyond 48 hours to avoid catabolism 3, 2
• Nitrogen scavengers will be dialyzed during CKRT but can still be effective when used concurrently 1, 2
• In liver failure patients, consider additional strategies like probiotics and rifaximin to reduce ammonia production in the gut 8, 9