How to manage hyperammonemia (elevated ammonia) in a patient?

Management of Hyperammonemia

The management of hyperammonemia requires immediate intervention with nitrogen-scavenging agents, dietary protein restriction, and consideration of renal replacement therapy for ammonia levels >150 μmol/L with neurological deterioration. 1

Initial Assessment and Treatment

Immediate Interventions

• Immediately conduct investigations while initiating treatment when elevated ammonia levels are detected 2, 1
• For ammonia levels >150 μmol/L with neurological deterioration:
  • Initiate Continuous Kidney Replacement Therapy (CKRT) immediately
  • Start nitrogen-scavenging agents
  • Consider plasma exchange when available 1

Dietary Management

• Discontinue all oral feeds temporarily 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
• Provide lipids (0.5 g/kg daily, up to 3 g/kg daily) 2, 1
• Gradually reintroduce protein (by 0.25 g/kg daily, up to 1.5 g/kg daily) within 48 hours once ammonia levels decrease to 80-100 μmol/L 2, 1

Pharmacological Management

Nitrogen-Scavenging Agents

For ammonia levels >150 μmol/L:

• Sodium benzoate:

  • Body weight <20 kg: 250 mg/kg
  • Body weight >20 kg: 5.5 g/m²
  • Given over 90 min as bolus then as maintenance over 24 h
  • Maximum dose: 12 g daily (high-dose benzoate can be toxic) 2, 1, 3

• Sodium phenylacetate:

  • Body weight <20 kg: 250 mg/kg
  • Body weight >20 kg: 5.5 g/m²
  • Given over 90 min as bolus then as maintenance over 24 h 2, 1, 3

• L-arginine hydrochloride (for urea cycle disorders):

  • For OTC and CPS deficiencies:
    • Body weight <20 kg: 200 mg/kg
    • Body weight >20 kg: 4 g/m²
  • For ASS and ASL deficiencies:
    • Body weight <20 kg: 600 mg/kg
    • Body weight >20 kg: 12 g/m²
  • Given over 90 min as bolus then as maintenance over 24 h 2, 3

Lactulose Therapy

• Start with 25-30 mL orally every 1-2 hours until bowel movements occur
• Maintain 2-3 soft bowel movements daily 1
• Particularly important for patients with liver disease 4

Renal Replacement Therapy

Indications for CKRT/Hemodialysis

• Ammonia levels >400 μmol/L with moderate or severe encephalopathy
• Ammonia levels >300 μmol/L with rapid rise
• Ammonia levels >150 μmol/L with rapidly deteriorating neurological status, coma, or cerebral edema
• Refractory to medical management 1

Choice of Modality

• Intermittent hemodialysis is more effective than peritoneal dialysis for rapid ammonia removal 2
• CKRT is preferred for hemodynamically unstable patients
• Continue nitrogen-scavenging agents during dialysis to prevent rebound hyperammonemia 1

Special Considerations

Monitoring

• Plasma ammonia, glutamine, quantitative plasma amino acids
• Blood glucose, electrolytes, venous or arterial blood gases
• AST and ALT
• Neurological status, Glasgow Coma Scale
• CT or MRI for cerebral edema 1, 3

Addressing Underlying Causes

• Identify and treat infections (common trigger)
• Investigate and treat GI bleeding
• Manage kidney injury
• Treat constipation 1
• For patients with short bowel syndrome and hyperammonemia, consider arginine supplementation 2

Blood Sampling Technique

• Use EDTA or lithium heparin tube
• Transport on ice to laboratory
• Process within 15 minutes of collection 1

Cautions and Pitfalls

• Do not rely solely on ammonia levels for clinical management - clinical status should guide therapy 5
• Avoid prolonged protein restriction beyond 48 hours as protein catabolism will drive further ammonia production 2, 1
• Monitor for hyperchloremic acidosis with high-dose arginine hydrochloride administration 3
• Ammonia levels ≥600 μg/dL (360 μmol/L) can cause significant brain damage; hemodialysis should be initiated promptly 6
• Administration of sodium phenylacetate through a peripheral IV catheter may cause burns; use central venous catheter 3

By following this structured approach to hyperammonemia management, focusing on rapid reduction of ammonia levels while addressing underlying causes, patient outcomes can be optimized with reduced risk of neurological sequelae.