What is the appropriate management for a patient with hyperammonemia?

Management of Arterial Ammonia 110 μmol/L

For an arterial ammonia level of 110 μmol/L, initiate immediate treatment with temporary protein restriction, intravenous glucose and lipid supplementation for caloric support, and close neurological monitoring, but hold nitrogen scavengers and dialysis unless the patient develops encephalopathy or ammonia levels rise above 150 μmol/L. 1

Immediate Stabilization and Assessment

• Secure airway, breathing, and circulation immediately, with intubation if neurological status is compromised 1
• Establish venous access for fluid and medication administration 2
• Assess neurological status carefully for early signs of encephalopathy including lethargy, somnolence, disorientation, or hyperventilation with respiratory alkalosis 1
• Obtain diagnostic workup to identify the underlying cause while treatment is initiated—do not delay treatment waiting for results 3

Nutritional Management (Critical First Step)

• Stop all protein intake immediately to reduce nitrogen load and prevent further ammonia production 1, 2, 3
• Administer intravenous glucose at 8-10 mg/kg/min to prevent catabolism and protein breakdown 1, 2, 3
• Provide intravenous lipids starting at 0.5 g/kg daily (up to 3 g/kg daily) for additional caloric support 1, 2, 3
• Ensure total caloric intake reaches ≥100 kcal/kg daily to prevent endogenous protein catabolism 1, 2, 3
• Reintroduce protein within 48 hours once ammonia decreases to 80-100 μmol/L—prolonged restriction beyond 48 hours causes harmful catabolism 1, 3

Pharmacological Therapy Thresholds

At Current Level (110 μmol/L):

• Nitrogen scavengers are NOT yet indicated at 110 μmol/L, as they are generally reserved for levels >150 μmol/L 1
• Monitor ammonia levels every 3-4 hours to detect rising trends 2, 3

If Ammonia Rises Above 150 μmol/L:

• Administer intravenous sodium benzoate and sodium phenylacetate 1, 3:

  • If weight <20 kg: 250 mg/kg loading dose over 90 minutes, then maintenance over 24 hours 1, 3
  • If weight >20 kg: 5.5 g/m² loading dose over 90 minutes, then maintenance over 24 hours 1, 3

• Add L-arginine hydrochloride if urea cycle disorder is suspected 1, 3:

  • For OTC/CPS deficiencies: 200 mg/kg (weight <20 kg) or 4 g/m² (weight >20 kg) 1
  • For ASS/ASL deficiencies: 600 mg/kg (weight <20 kg) or 12 g/m² (weight >20 kg) 1

• Add L-carnitine ONLY if organic acidemia is suspected (NOT for urea cycle disorders): 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg daily 3

Kidney Replacement Therapy Indications

At Current Level (110 μmol/L):

• Dialysis is NOT indicated at 110 μmol/L unless there is rapidly deteriorating neurological status or coma 1

Consider Dialysis If:

• Ammonia levels exceed 300-400 μmol/L despite medical therapy 1, 3
• Rapidly deteriorating neurological status or coma develops 1, 3
• Signs of moderate to severe encephalopathy appear 1
• Cerebral edema is present with ammonia >150 μmol/L 1

Dialysis Modality Selection:

• High-dose continuous venovenous hemodialysis (CVVHD) is first-line when available (blood flow 30-50 mL/min, dialysis fluid flow/Qb ratio >1.5) 3
• Intermittent hemodialysis is most effective for rapid ammonia reduction (95-96% filtration fraction, 50% reduction in 1-3 hours) but carries risk of post-dialytic rebound 1, 3
• Peritoneal dialysis should only be used if other modalities are unavailable 1, 3

Monitoring Protocol

• Check plasma ammonia levels every 3-4 hours until normalized 2, 3
• Assess neurological status regularly for progression of encephalopathy 2, 3
• Monitor electrolytes, especially if dialysis is initiated 2, 3

Critical Pitfalls to Avoid

• Delayed treatment is the most important prognostic factor—duration of hyperammonemic coma >3 days or peak levels >1,000 μmol/L predict poor outcomes 1, 3
• Ammonia samples must be collected from free-flowing venous or arterial blood, transported on ice, and processed within 15 minutes to avoid falsely elevated results 1, 2, 3
• Do not restrict protein beyond 48 hours as this induces catabolism and worsens hyperammonemia 1, 2, 3
• Nitrogen scavengers will be dialyzed during kidney replacement therapy but remain effective when used concurrently 1, 3

Context for Hepatic Encephalopathy

If this hyperammonemia is secondary to cirrhosis and hepatic encephalopathy, lactulose is the primary treatment, reducing blood ammonia by 25-50% through colonic acidification and trapping ammonia as ammonium ion 4, 5. However, ammonia levels do not correlate with lactulose dosing in clinical practice and should not guide therapy intensity in hepatic encephalopathy 6.