Treatment of Hyperammonemia
The treatment of hyperammonemia requires immediate intervention with a combination of protein restriction, nitrogen scavengers, and kidney replacement therapy for severe cases to prevent irreversible neurological damage and reduce mortality. 1, 2
Initial Management
- Immediately stabilize the patient (airway, breathing, circulation) and establish intravenous access when hyperammonemia is identified 3
- Stop all protein intake temporarily to reduce nitrogen load and prevent further ammonia production 1, 2
- Administer intravenous glucose (8-10 mg/kg/min) and lipids (starting at 0.5 g/kg daily, up to 3 g/kg daily) to provide adequate calories (≥100 kcal/kg daily) and prevent catabolism 1, 2
- Monitor plasma ammonia levels every 3 hours until normalized 1, 3
- Reintroduce protein within 48 hours after ammonia levels decrease to 80-100 μmol/L to avoid catabolism 3, 1
Pharmacological Therapy
Nitrogen Scavengers
- Administer intravenous sodium benzoate and sodium phenylacetate as first-line medications to remove excess ammonia 1, 4
- Dosage is weight-dependent: 250 mg/kg for patients <20 kg and 5.5 g/m² for patients >20 kg 1, 4
- Administer as a loading dose over 90-120 minutes followed by maintenance infusion over 24 hours 4, 2
Urea Cycle Intermediates
Additional Medications
- For organic acidemias, add L-carnitine: 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg daily 1, 5
- Consider lactulose or rifaximin for hepatic encephalopathy to reduce intestinal ammonia production 6, 7
Kidney Replacement Therapy (KRT)
- Consider KRT when ammonia levels exceed 300-400 μmol/L despite medical therapy or with signs of moderate to severe encephalopathy 1, 2
- Hemodialysis is the most effective method for rapidly reducing blood ammonia levels with 95-96% filtration fraction 1, 2
- Continuous kidney replacement therapy (CKRT) is an alternative when hemodialysis is not available 3
- Success rates vary by modality: 100% for intermittent hemodialysis, 60% for CKRT, and 65% for peritoneal dialysis 3
- Continue KRT until ammonia levels are <200 μmol/L on at least two consecutive measurements 2, 1
Monitoring During Treatment
- Check plasma ammonia levels every 3-4 hours until normalized 1, 2
- Assess neurological status regularly for signs of encephalopathy 1, 8
- Monitor electrolytes, blood glucose, acid-base status, and liver function tests 1, 4
- Two factors determine prognosis of neurological damage: duration of hyperammonemic coma and plasma ammonia levels 3, 8
Cause-Specific Considerations
- For liver failure: Consider lactulose, rifaximin, and probiotics to reduce intestinal ammonia production 6, 9
- For urea cycle disorders: Focus on nitrogen scavengers and arginine supplementation 4, 10
- For organic acidemias: Add L-carnitine to treatment regimen 1, 7
- For transient hyperammonemia of newborns: Usually self-resolving but may require supportive care 3, 7
Common Pitfalls and Caveats
- Delayed recognition and treatment can lead to irreversible neurological damage, including seizures, coma, and death 1, 8
- Ammonia samples must be collected from free-flowing venous or arterial blood, transported on ice, and processed within 15 minutes to avoid false elevations 1, 3
- Protein restriction should not be prolonged beyond 48 hours to avoid catabolism 1, 3
- Nitrogen scavengers will be dialyzed during CKRT but can still be effective when used concurrently 1, 2
- Adverse prognostic factors include hyperammonemic coma lasting >3 days, increased intracranial pressure, and/or plasma ammonia levels >1,000 μmol/L 3, 8