Treatment of Hyperammonemia
Hyperammonemia treatment should include both rapid ammonia removal through hemodialysis for severe cases (>150 μmol/L with neurological deterioration) and pharmacological interventions with nitrogen-scavenging agents like sodium phenylacetate and sodium benzoate. 1
Initial Assessment and Stratification
- Measure blood ammonia levels and assess neurological status using Glasgow Coma Scale
- Normal ammonia range in adults: 16-53 μmol/L 1
- Ensure proper blood sampling technique:
- Use EDTA or lithium heparin tube
- Transport on ice to laboratory
- Process within 15 minutes of collection
Treatment Thresholds Based on Ammonia Levels
| Clinical Scenario | Ammonia Level | Recommended Action |
|---|---|---|
| Rapidly deteriorating neurological status | >150 μmol/L | Initiate CKRT |
| Moderate/severe encephalopathy | Any level | Consider treatment |
| Persistently high levels | >400 μmol/L | Initiate CKRT if refractory to medical management |
| Rapid rise in levels | >300 μmol/L | Initiate CKRT if uncontrolled by medical therapy |
Dialysis-Based Interventions
Intermittent Hemodialysis (HD)
- First-line for hemodynamically stable patients with severe hyperammonemia
- Provides rapid clearance (75% reduction within 3-4 hours)
- Optimization parameters:
- Higher blood flow rates
- Larger surface area dialyzers
- Dialysate flow rate to blood flow rate ratio >1.5
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
Sustained Low-Efficiency Dialysis (SLED)
- Consider for moderate urgency with hemodynamic concerns
Pharmacological Management
Nitrogen-Scavenging Agents
Sodium Phenylacetate and Sodium Benzoate
- Dosage based on body weight 2:
- <20 kg: 250 mg/kg of each agent
20 kg: 5.5 g/m² of each agent
- Administration:
- Loading dose over 90-120 minutes
- Followed by maintenance dose over 24 hours
- Maximum daily dose: 12 g
- Must be diluted with sterile 10% Dextrose Injection before administration
- Administer via central venous catheter only
L-arginine Hydrochloride
- For urea cycle disorders
- Dosage varies by deficiency type:
- CPS/OTC deficiency: 200 mg/kg
- ASS/ASL deficiency: 600 mg/kg
- Monitor for hyperchloremic acidosis
Nutritional Support
- Temporarily withdraw protein 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):
- Intravenous glucose (8-10 mg/kg/min)
- Lipids (0.5-3 g/kg daily)
Monitoring and Follow-up
- Measure ammonia levels at 24 hours and 5-7 days
- Monitor neurological status continuously
- Track electrolytes, particularly glucose, potassium, magnesium, and phosphate
- Assess acid-base status
- Continue treatment until:
- Clinical improvement observed
- Improved mental status
- Resolution of neurological symptoms
- Adequate reduction in ammonia levels
- Hemodynamic stability
Special Considerations
- Hemodialysis should be considered in patients with severe hyperammonemia or who are not responsive to pharmacological management
- Duration of hyperammonemic coma and plasma ammonia levels are key prognostic factors
- Adverse prognostic factors:
- Hyperammonemic coma lasting >3 days
- Increased intracranial pressure
- Plasma ammonia level >1,000 μmol/L
Common Pitfalls to Avoid
- Delaying treatment initiation while awaiting confirmatory tests
- Using peripheral IV access for nitrogen-scavenging agents (can cause burns)
- Failing to monitor for rebound hyperammonemia after intermittent HD
- Neglecting to provide adequate caloric support during protein restriction
- Administering repeat loading doses of nitrogen-scavenging agents (contraindicated due to prolonged plasma levels)
- Overlooking infections as common triggers for encephalopathy