What is the treatment for hyperammonemia?

Treatment for Hyperammonemia

The treatment for hyperammonemia requires immediate initiation of continuous kidney replacement therapy (CKRT) for ammonia levels >400 μmol/L refractory to medical management, or rapid rise in ammonia levels >300 μmol/L within hours, along with nitrogen-scavenging agents and temporary protein restriction. 1, 2

Initial Medical Management

First-line Interventions

• Stop protein intake immediately and monitor ammonia levels every 3 hours
• Provide adequate calories (≥100 kcal/kg daily) as intravenous glucose and lipids
• Maintain glucose infusion rate of 8-10 mg/kg/min with lipids (0.5 g/kg daily, up to 3 g/kg daily)
• Administer nitrogen-scavenging agents:
  • Sodium benzoate:
    • 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
    • Maximum dose: 12 g daily
  • 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

Additional Medications

• Lactulose: Starting dose 25-30 mL orally every 1-2 hours until bowel movements occur, then adjust to maintain 2-3 soft bowel movements daily 2
• Rifaximin: 550 mg orally twice daily for ammonia levels >150 μmol/L with neurological symptoms 2
• L-arginine hydrochloride: Dosage based on type of urea cycle disorder
  • 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

Renal Replacement Therapy

Indications for Renal Replacement Therapy

• Rapidly deteriorating neurological status, coma, or cerebral edema
• Persistently high blood ammonia levels >400 μmol/L refractory to medical management
• Rapid rise in ammonia levels >300 μmol/L within hours not controlled by medical measures 1, 2

Types of Renal Replacement Therapy

1. Continuous Kidney Replacement Therapy (CKRT):

   • Preferred for hemodynamically unstable patients
   • Prevents rebound hyperammonemia
   • Recommended clearance rates ≥2,500 ml/1.73 m²/h for high-dose CKRT
   • CVVHD (continuous venovenous hemodialysis) provides higher ammonia clearance than CVVH

2. Intermittent Hemodialysis (HD):

   • For rapid ammonia clearance when immediate reduction is needed
   • Blood flow rate (Qb) of 30-50 ml/min
   • Dialysate flow rate (Qd) to blood flow rate (Qb) ratio >1.5

3. Peritoneal Dialysis (PD):

   • Only recommended when other modalities of kidney replacement therapy are unavailable
   • Less efficient than HD or CKRT
   • Rigid peritoneal catheters are not recommended due to increased complications 1

4. Hybrid Therapy:

   • HD followed by CKRT for extremely high ammonia levels (>1,000 μmol/L) 2

Nutritional Management

• Temporarily withdraw protein during acute phase
• Reintroduce protein within 48 hours after ammonia levels decrease to 80-100 μmol/L to avoid catabolism
• Gradual reintroduction (0.25 g/kg daily, up to 1.5 g/kg daily) 1, 2

Monitoring and Follow-up

• Monitor plasma ammonia levels every 3 hours during acute phase
• Assess neurological status continuously using Glasgow Coma Scale
• Check electrolytes, blood glucose, venous or arterial blood gases, AST, and ALT
• Ensure proper blood sampling technique for accurate ammonia measurement:
  • Use EDTA or lithium heparin tube
  • Transport on ice to laboratory
  • Process within 15 minutes of collection 2

Important Considerations

• Duration of hyperammonemic coma and plasma ammonia levels are key prognostic factors
• Adverse prognostic factors include:
  • Hyperammonemic coma lasting >3 days
  • Increased intracranial pressure
  • Plasma ammonia level >1,000 μmol/L 1
• Identify and address underlying causes (liver disease, urea cycle disorders, organic acidurias, etc.)
• Repeat loading doses of nitrogen-scavenging agents should not be administered due to prolonged plasma levels 3

Pitfalls to Avoid

1. Delayed initiation of treatment: Start treatment immediately when hyperammonemia is detected
2. Prolonged protein restriction: Protein must be reintroduced within 48 hours to prevent catabolism
3. Inadequate caloric intake: Insufficient calories can lead to catabolism and worsen hyperammonemia
4. Relying solely on ammonia levels: Clinical status should guide management decisions
5. Failure to consider dialysis early: Don't delay renal replacement therapy when indicated
6. Peripheral administration of medications: Sodium phenylacetate and sodium benzoate must be administered via central venous catheter to avoid burns 3

The most important prognostic factor is the duration of hyperammonemic coma prior to the start of dialysis, highlighting the critical importance of early and aggressive intervention in the management of hyperammonemia 1.