Treatment of Hyperammonemia in Non-Cirrhosis Patients
Hyperammonemia in non-cirrhosis patients should be treated with a combination of pharmacological therapy using nitrogen-scavenging agents and hemodialysis for severe cases, with intermittent hemodialysis recommended for rapid ammonia clearance in patients with neurological deterioration. 1, 2
Initial Assessment and Treatment Decision
- Measure ammonia levels and assess neurological status using Glasgow Coma Scale
- Treatment approach depends on:
- Ammonia level
- Neurological status
- Hemodynamic stability
Treatment Algorithm Based on Ammonia Levels
| Clinical Scenario | Ammonia Level | Recommended Action |
|---|---|---|
| Rapidly deteriorating neurological status | >150 μmol/L | Initiate dialysis |
| Coma or cerebral edema | >150 μmol/L | Initiate dialysis |
| Moderate/severe encephalopathy | >400 μmol/L | Initiate dialysis |
| Ammonia levels not decreasing | >150 μmol/L after 4-8 hours of medical therapy | Initiate dialysis |
Pharmacological Management
Nitrogen-Scavenging Agents
Sodium phenylacetate and sodium benzoate:
- Loading dose: 0.25 g/kg of each component
- Administered over 90-120 minutes
- Followed by maintenance infusion of the same dose over 24 hours
- Continue until ammonia levels normalize or oral therapy can be started 3
L-arginine supplementation:
- Essential for patients with urea cycle enzyme deficiencies
- Monitor for hyperchloremic acidosis during administration 3
Nutritional Support
- Temporarily withdraw protein during acute phase
- Reintroduce protein within 48 hours after ammonia levels decrease to 80-100 μmol/L
- Provide adequate calories (≥100 kcal/kg daily) as intravenous glucose and lipids
- Maintain glucose infusion rate of 8-10 mg/kg/min 2
Dialysis Therapy
Intermittent Hemodialysis
- First-line therapy for rapid ammonia clearance
- Can decrease blood ammonia by 75% within 3-4 hours
- Indicated for:
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 2
Hybrid Therapy
- Combination of HD and CKRT (sequential therapy)
- Start with HD for rapid reduction of ammonia levels
- Follow with CKRT to prevent rebound effect
- Transition to CKRT once ammonia levels <200 μmol/L on two consecutive measurements 1
Monitoring During Treatment
- Frequent monitoring of:
Pitfalls and Considerations
- Rebound hyperammonemia: Common after intermittent HD; consider hybrid therapy or continuing nitrogen-scavenging agents during dialysis
- Cerebral edema risk: Rapid osmolarity shifts during HD can worsen cerebral edema; monitor osmolarity regularly
- Hemodynamic instability: Consider CKRT instead of HD in unstable patients
- Vascular access: May be challenging in neonates and infants; peripheral artery and umbilical vein access has been used successfully 1
- Electrolyte imbalances: Monitor and correct electrolytes during treatment to prevent complications 2
Additional Measures
For patients with intestinal sources of ammonia production, consider:
- Oral or rectal neomycin
- Lactulose to reduce intestinal ammonia production 4
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
The treatment approach should be aggressive as persistent hyperammonemia can lead to irreversible neurological damage, with duration of hyperammonemic coma and plasma ammonia levels being key prognostic factors 2, 5.