Treatment for Hyperammonemia
The treatment for hyperammonemia requires a combination of pharmacological therapy using nitrogen-scavenging agents and hemodialysis for severe cases, with specific interventions based on ammonia levels and clinical presentation. 1
Initial Assessment and Treatment Decision
- Ammonia level of 92 μmol/L requires treatment but does not necessarily warrant immediate dialysis
- Treatment approach depends on:
- Neurological status (presence of encephalopathy)
- Rate of rise of ammonia levels
- Underlying cause (cirrhotic vs. non-cirrhotic)
Pharmacological Management
First-Line Medications
Lactulose
- FDA-approved for portal-systemic encephalopathy
- Reduces blood ammonia levels by 25-50%
- Clinical response observed in approximately 75% of patients 2
- Mechanism: Reduces ammonia production and absorption in the gut
Nitrogen-Scavenging Agents (for non-cirrhotic causes)
Sodium benzoate:
- Dosage: 250 mg/kg for body weight <20 kg; 5.5 g/m² for body weight >20 kg
- Administration: Given over 90 min as bolus, then as maintenance over 24 hours
- Maximum dose: 12 g daily 1
Sodium phenylacetate:
- Dosage: 250 mg/kg for body weight <20 kg; 5.5 g/m² for body weight >20 kg
- Administration: Given over 90 min as bolus, then as maintenance over 24 hours 1
L-arginine hydrochloride (specifically for urea cycle disorders)
- Dosage based on type of deficiency and patient weight 1
Dialysis Indications
Hemodialysis should be initiated for:
- Rapidly deteriorating neurological status with ammonia >150 μmol/L
- Coma or cerebral edema with ammonia >150 μmol/L
- Moderate or severe encephalopathy with ammonia >400 μmol/L
- Rapid rise in blood ammonia levels >300 μmol/L
- Failure to respond to pharmacological therapy 1
Dialysis Modalities
Intermittent Hemodialysis (HD)
- Most efficient for rapid ammonia clearance (75% reduction within 3-4 hours)
- Indicated for neurological deterioration 1
Continuous Kidney Replacement Therapy (CKRT)
- Preferred for hemodynamically unstable patients
- Prevents rebound hyperammonemia
- Recommended clearance rates ≥2,500 ml/1.73 m²/h 1
Hybrid 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 1
Nutritional Management
- Acute Phase: Temporarily withdraw protein
- Recovery Phase: Reintroduce protein when ammonia levels decrease to 80-100 μmol/L (within 48 hours)
- Caloric Support: Provide ≥100 kcal/kg daily as IV glucose and lipids
- Glucose Infusion: Maintain rate of 8-10 mg/kg/min
- Lipids: 0.5 g/kg daily, up to 3 g/kg daily 1
Monitoring
- Measure ammonia levels at 24 hours and 5-7 days
- Continuously assess neurological status using Glasgow Coma Scale
- Monitor for rebound hyperammonemia, especially after intermittent HD 1
Supportive Care
- Ensure adequate volume replacement and maintain mean arterial pressure
- Use vasopressors as needed
- Correct electrolyte abnormalities (glucose, potassium, magnesium, phosphate)
- Treat acid-base disturbances
- Consider vitamin D3 supplementation in critically ill patients
- Administer vitamin K in coagulopathic patients
- Screen for and treat infections promptly 1
Clinical Pitfalls and Caveats
Rebound Hyperammonemia: Common after intermittent HD; prevent by continuing nitrogen-scavenging agents during dialysis
Delayed Treatment: Any delay in recognition and treatment may have serious neurological consequences 3
Ammonia Levels vs. Clinical Status: Treatment decisions should consider both ammonia levels and neurological status, as the correlation is not always perfect
Underlying Cause: Treatment approach may differ based on whether hyperammonemia is due to liver failure, urea cycle disorders, or other causes
Brain Damage Risk: Ammonia levels ≥600 μg/dL (360 μmol/L) can cause significant brain damage, requiring immediate intervention 3