Initial Management of Hyperammonemia in Non-Cirrhotic Patients
The initial management of hyperammonemia in non-cirrhotic patients requires prompt treatment with nitrogen-scavenging agents and hemodialysis for severe cases, with intermittent hemodialysis recommended for rapid ammonia clearance in patients with neurological deterioration. 1
Immediate Assessment and Indications for Treatment
- Measure ammonia levels and assess neurological status using the Glasgow Coma Scale
- Initiate treatment based on ammonia levels and clinical presentation:
| 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 |
Pharmacological Management
Nitrogen-Scavenging Agents
Sodium Phenylacetate and Sodium Benzoate:
- Dosage: 0.25 g/kg (or 5.5 g/m²) of each agent
- Administration: Bolus dose over 90-120 minutes, followed by maintenance infusion over 24 hours 2
- For patients >20 kg: 5.5 g/m²
- For patients <20 kg: 250 mg/kg
- Maximum dose: 12 g daily
L-arginine hydrochloride:
- Essential for patients with specific urea cycle disorders (CPS, OTC, ASS, or ASL deficiency)
- Monitor chloride and bicarbonate levels due to risk of hyperchloremic acidosis
Dialysis Therapy
Intermittent hemodialysis (HD): First-line for rapid ammonia clearance
- Can decrease blood ammonia by 75% within 3-4 hours
- Indicated for:
- Rapidly deteriorating neurological status
- Coma or cerebral edema
- Ammonia levels >1,000 μmol/L
- Failure to respond to pharmacological therapy
Combination approach:
- Start with HD for rapid reduction
- Transition to CKRT once ammonia levels <200 μmol/L on two consecutive measurements
- Continue nitrogen-scavenging agents during dialysis to prevent rebound hyperammonemia
Nutritional Support
- Temporarily withdraw protein during acute phase
- Provide adequate calories (≥100 kcal/kg daily) as intravenous glucose and lipids
- Maintain glucose infusion rate of 8-10 mg/kg/min
- Add lipids (0.5 g/kg daily, up to 3 g/kg daily)
- Reintroduce protein within 48 hours after ammonia levels decrease to 80-100 μmol/L
- Gradually increase protein (0.25 g/kg daily, up to 1.5 g/kg daily)
Supportive Care
- Ensure adequate volume replacement and maintain mean arterial pressure
- Use vasopressors (dopamine, epinephrine, norepinephrine) as needed
- Correct electrolyte abnormalities (glucose, potassium, magnesium, phosphate)
- Treat acid-base disturbances
- Consider antibiotic prophylaxis in high-risk patients
- Administer appropriate antibiotics promptly when infection is identified
Monitoring
- Check ammonia levels at 24 hours and 5-7 days
- Monitor neurological status continuously
- Consider hemodialysis if plasma ammonia levels fail to fall below 150 μmol/L or by more than 40% within 4-8 hours after receiving nitrogen-scavenging agents 2
Pitfalls and Caveats
- Delayed recognition and treatment can lead to irreversible neurological damage
- Rebound hyperammonemia is common after intermittent HD; consider hybrid therapy
- Administration of sodium phenylacetate and sodium benzoate through peripheral IV can cause burns; use central venous catheter 2
- Terminate oral nitrogen-scavenging medications prior to IV administration
- Non-cirrhotic hyperammonemia can have various etiologies including urea cycle disorders, certain infections (e.g., Ureaplasma species), and metabolic disorders that require specific diagnostic workup