What is the treatment for hyperammonemia?

Treatment of Hyperammonemia

The treatment of hyperammonemia requires immediate intervention with nitrogen scavengers, temporary protein restriction, intravenous glucose supplementation, and consideration for kidney replacement therapy (KRT) based on ammonia levels and clinical status. 1

Initial Medical Management

• Immediately conduct further investigations while simultaneously initiating treatment when elevated ammonia levels are detected 2
• Discontinue all oral protein intake temporarily to prevent further ammonia production 1, 3
• Provide adequate calories (≥100 kcal/kg daily) through intravenous glucose and lipids to prevent catabolism 2, 1
• Maintain glucose infusion rate at 8-10 mg/kg/min 2, 1
• Administer intravenous lipids (0.5 g/kg daily, up to 3 g/kg daily) for caloric support 2, 1

Pharmacological Treatment

• Use nitrogen-scavenging agents at ammonia levels >150 μmol/L 1, 3:
  • Intravenous sodium benzoate (maximum dose 12 g daily):
    • For patients <20 kg: 250 mg/kg given over 90 min as bolus then as maintenance over 24 h 2
    • For patients >20 kg: 5.5 g/m² given over 90 min as bolus then as maintenance over 24 h 2
  • Intravenous sodium phenylacetate:
    • For patients <20 kg: 250 mg/kg given over 90 min as bolus then as maintenance over 24 h 2
    • For patients >20 kg: 5.5 g/m² given over 90 min as bolus then as maintenance over 24 h 2
• For suspected urea cycle disorders, add L-arginine hydrochloride 2, 1:
  • For OTC and CPS deficiencies:
    • Patients <20 kg: 200 mg/kg 2
    • Patients >20 kg: 4 g/m² 2
  • For ASS and ASL deficiencies:
    • Patients <20 kg: 600 mg/kg 2
    • Patients >20 kg: 12 g/m² 2
• For hepatic encephalopathy, administer lactulose, which reduces blood ammonia levels by 25-50% 4, 5

Kidney Replacement Therapy (KRT)

• Clinical status should be the primary determinant for initiating KRT 2
• Consider KRT for 2, 1:
  • Rapidly deteriorating neurological status, coma, or cerebral edema
  • Persistently high blood ammonia levels >400 μmol/L refractory to medical measures
  • Rapid rise in ammonia levels >300 μmol/L within a few hours that cannot be controlled via medical measures

KRT Modality Selection

• Continuous Kidney Replacement Therapy (CKRT) is the preferred first-line treatment due to fewer cardiovascular complications and lower risk of rebound hyperammonemia 2, 1
• Continuous venovenous hemodialysis (CVVHD) enables higher ammonia clearance than continuous venovenous hemofiltration (CVVH) 2
• Hemodialysis (HD) is most effective for rapidly reducing blood ammonia levels but has more complications than CKRT 1, 3
• Peritoneal dialysis (PD) should only be used when other KRT modalities are unavailable 2

Protein Reintroduction and Ongoing Management

• Gradually reintroduce protein (by 0.25 g/kg daily, up to 1.5 g/kg daily) within 48 hours after ammonia levels decrease 2, 1
• Avoid prolonged protein restriction beyond 48 hours as protein catabolism will drive further ammonia production 2, 1
• Monitor ammonia levels every 3-4 hours until normalized 3

Common Pitfalls and Caveats

• Delayed recognition and treatment can lead to irreversible neurological damage 1, 3
• Ammonia samples must be properly collected from free-flowing venous or arterial blood and processed quickly to avoid false elevations 1, 3
• Duration of hyperammonemic coma >3 days is associated with poor prognosis 1
• Nitrogen scavengers will be dialyzed along with ammonia during KRT but can still be effective when used concurrently 1, 3
• For hepatic encephalopathy specifically, ammonia levels do not consistently guide lactulose dosing in clinical practice 6