What is the treatment for hyperammonemia (elevated serum ammonia level)?

Treatment of Hyperammonemia (Elevated Serum Ammonia Level)

Immediate continuous kidney replacement therapy (CKRT) is the first-line treatment for severe hyperammonemia with ammonia levels >400 μmol/L refractory to medical management, or rapid rise in ammonia levels >300 μmol/L within hours. 1

Treatment Algorithm Based on Ammonia Level and Clinical Status

Severe Hyperammonemia (>400 μmol/L or rapidly rising >300 μmol/L)

1. Kidney Replacement Therapy

   • First choice: CKRT (Continuous Kidney Replacement Therapy) 1
     • Preferred for hemodynamically unstable patients
     • Prevents rebound hyperammonemia
     • Target clearance rates ≥2,500 ml/1.73 m²/h for high-dose CKRT
   • Alternative: Intermittent Hemodialysis 2, 1
     • For rapid ammonia clearance when immediate reduction needed
     • Blood flow rate: 30-50 ml/min
     • Dialysate flow rate to blood flow rate ratio >1.5
   • Last resort: Peritoneal Dialysis (only when other modalities unavailable) 2
     • Less efficient than HD or CKRT
     • Avoid rigid peritoneal catheters due to increased complications

2. Concurrent Pharmacological Treatment

   • Nitrogen-scavenging agents 1
     • Sodium benzoate: 250 mg/kg for weight <20 kg; 5.5 g/m² for weight >20 kg
       • Given over 90 min as bolus then maintenance over 24 hours
       • Maximum dose: 12 g daily
     • Sodium phenylacetate: 250 mg/kg for weight <20 kg; 5.5 g/m² for weight >20 kg
       • Given over 90 min as bolus then maintenance over 24 hours
     • L-arginine hydrochloride for urea cycle disorders

Moderate Hyperammonemia (150-400 μmol/L)

1. Pharmacological Treatment

   • Lactulose 3
     • Mechanism: Reduces blood ammonia by:
       • Acidifying colonic contents
       • Converting NH3 to NH4+ (ammonium ion), trapping it in colon
       • Expelling trapped ammonium through laxative action
     • Dosage: Titrate to achieve 2-3 soft bowel movements daily

2. Dietary Management 1

   • Temporary protein restriction during acute phase
   • Reintroduce protein within 48 hours after ammonia levels decrease to 80-100 μmol/L
   • Gradual reintroduction: 0.25 g/kg daily, up to 1.5 g/kg daily
   • Provide adequate calories (≥100 kcal/kg daily) as IV glucose and lipids

Supportive Care (All Patients)

1. Maintain hemodynamic stability 1

   • Adequate volume replacement
   • Maintain mean arterial pressure
   • Use vasopressors if needed (dopamine, epinephrine, norepinephrine)

2. Correct electrolyte abnormalities 1

   • Particularly glucose, potassium, magnesium, and phosphate

3. Treat underlying causes

   • Identify and address triggers (infection, GI bleeding, etc.)
   • Administer appropriate antibiotics promptly when infection identified

Monitoring

• Measure ammonia levels at 24 hours and 5-7 days 1
• Assess neurological status using Glasgow Coma Scale
• Monitor for signs of cerebral edema

Important Clinical Considerations

Prognostic Factors

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

Common Pitfalls to Avoid

1. Delayed recognition and treatment

   • Hyperammonemia is a medical emergency requiring immediate intervention to prevent neurological damage
   • Don't wait for severe encephalopathy to initiate treatment

2. Inadequate ammonia monitoring

   • Ensure proper blood sampling technique:
     • Use EDTA or lithium heparin tube
     • Transport on ice to laboratory
     • Process within 15 minutes of collection

3. Relying solely on medical management for severe hyperammonemia

   • Dialysis is essential for rapid ammonia removal in severe cases
   • Pharmacological treatments alone may be insufficient

4. Prolonged protein restriction

   • Extended protein restriction can lead to catabolism, which increases ammonia production
   • Reintroduce protein within 48 hours after ammonia levels decrease

5. Neglecting supportive care

   • Maintain adequate caloric intake to prevent catabolism
   • Address electrolyte imbalances and hemodynamic instability

The treatment approach should be guided by the severity of hyperammonemia and the patient's clinical status, with immediate CKRT for severe cases and comprehensive medical management for all patients.