What is the treatment for hyperammonemia?

Treatment of Hyperammonemia

The treatment of hyperammonemia requires immediate intervention with nitrogen-scavenging agents and hemodialysis for severe cases, with intermittent hemodialysis recommended for rapid ammonia clearance in patients with neurological deterioration. 1

First-Line Pharmacological Treatment

• Nitrogen-scavenging medications:
  • Sodium phenylacetate and sodium benzoate:
    • For patients ≤20 kg: 250 mg/kg of each medication
    • For patients >20 kg: 5.5 g/m² of each medication
    • Administered as loading dose over 90-120 minutes, followed by maintenance dose over 24 hours 2
  • L-arginine hydrochloride: Used specifically for urea cycle disorders
    • For CPS/OTC deficiency: 200 mg/kg
    • For ASS/ASL deficiency: 600 mg/kg 1, 2

Dialysis Therapy

• Indications for immediate hemodialysis:

  • Rapidly deteriorating neurological status with ammonia >150 μmol/L
  • Coma or cerebral edema with ammonia >150 μmol/L
  • Moderate/severe encephalopathy with ammonia >400 μmol/L
  • Rapid rise in ammonia levels >300 μmol/L
  • Ammonia levels >1,000 μmol/L
  • Failure to respond to pharmacological therapy 1

• Dialysis modality selection:

  • Intermittent hemodialysis (HD): First-line for rapid ammonia reduction (can decrease blood ammonia by 75% within 3-4 hours)
  • Continuous Kidney Replacement Therapy (CKRT): For hemodynamically unstable patients and to prevent rebound hyperammonemia
  • Hybrid approach: Start with HD for rapid reduction, then transition to CKRT once ammonia levels <200 μmol/L on two consecutive measurements 1

Nutritional Management

• Acute phase:

  • Temporarily withdraw protein
  • Provide adequate calories (≥100 kcal/kg daily) via intravenous glucose and lipids
  • Maintain glucose infusion rate of 8-10 mg/kg/min
  • Administer lipids (0.5 g/kg daily, up to 3 g/kg daily) 1, 2

• Recovery phase:

  • Reintroduce protein within 48 hours after ammonia levels decrease to 80-100 μmol/L
  • Gradual reintroduction starting at 0.25 g/kg daily, increasing up to 1.5 g/kg daily 1

Monitoring Protocol

• Measure ammonia levels at 24 hours and 5-7 days
• Continuously assess neurological status using Glasgow Coma Scale
• Monitor electrolytes, blood glucose, venous or arterial blood gases, liver enzymes, and quantitative plasma amino acids 1, 2

Special Considerations

• Rebound prevention: Consider continuing nitrogen-scavenging agents during dialysis 1
• Supportive care:
  • Ensure adequate volume replacement and maintain mean arterial pressure
  • Use vasopressors as needed
  • Correct electrolyte abnormalities (glucose, potassium, magnesium, phosphate)
  • Treat acid-base disturbances
  • Consider vitamin D3 supplementation in critically ill patients
  • Administer vitamin K in coagulopathic patients
  • Perform surveillance for infections and administer antibiotics promptly when identified 1

Prognostic Factors

• Duration of hyperammonemic coma (>3 days indicates poor prognosis)
• Plasma ammonia levels (>1,000 μmol/L indicates poor prognosis)
• Increased intracranial pressure 1

Clinical Pitfalls to Avoid

• Delayed recognition: Hyperammonemia is a medical emergency requiring immediate intervention
• Inadequate monitoring: Failure to monitor ammonia levels and neurological status can lead to missed opportunities for intervention
• Peripheral IV administration: Sodium phenylacetate and sodium benzoate must be administered via central venous catheter to avoid burns 2
• Repeat loading doses: Should not be administered due to prolonged plasma levels of phenylacetate 2
• Neglecting underlying causes: Treatment should address the specific etiology of hyperammonemia while managing the acute crisis

The treatment approach should be tailored based on the severity of hyperammonemia, the patient's clinical status, and the underlying cause, with the primary goal of rapidly reducing ammonia levels to prevent permanent neurological damage.