How to treat hyperammonemia with an ammonia level of 200 μmol/L?

Treatment of Hyperammonemia with Ammonia Level of 200 μmol/L

For a patient with an ammonia level of 200 μmol/L, initiate both medical management with nitrogen scavengers and consider continuous kidney replacement therapy (CKRT), specifically high-dose continuous venovenous hemodialysis (CVVHD), as this level represents a threshold for increased mortality risk, especially in liver failure. 1, 2

Initial Medical Management

• Stop protein intake immediately to prevent further ammonia production 1, 2
• Administer intravenous glucose at 8-10 mg/kg/min to prevent catabolism 1
• Provide intravenous lipids starting at 0.5 g/kg daily, up to 3 g/kg daily to ensure adequate caloric intake 1
• Target caloric intake of ≥100 kcal/kg daily to prevent protein breakdown 1

Pharmacological Therapy (Nitrogen Scavengers)

• Administer intravenous sodium benzoate and sodium phenylacetate as a bolus over 90-120 minutes followed by maintenance infusion over 24 hours 3:
  • For patients <20 kg: 250 mg/kg of each agent
  • For patients >20 kg: 5.5 g/m² of each agent
• Add intravenous L-arginine hydrochloride (dose depends on specific urea cycle disorder) 1, 3:
  • For OTC and CPS deficiencies: 200 mg/kg (<20 kg) or 4 g/m² (>20 kg)
  • For ASS and ASL deficiencies: 600 mg/kg (<20 kg) or 12 g/m² (>20 kg)
• For organic acidemias, add L-carnitine: 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg daily 1

Kidney Replacement Therapy

• At ammonia level of 200 μmol/L, CKRT should be strongly considered, especially if there is evidence of encephalopathy 1, 4
• CVVHD is the recommended first-line KRT modality for hyperammonemia 1
• Warm the dialysate to maintain hemodynamic stability 1, 5
• Target blood flow rate (Qb) of 30-50 ml/min with dialysate flow rate (Qd)/Qb >1.5 1
• Continue CKRT until ammonia levels are <200 μmol/L on at least two consecutive hourly measurements 1

Monitoring During Treatment

• Check plasma ammonia levels every 3-4 hours until normalized 1, 3
• Monitor glutamine, quantitative plasma amino acids, blood glucose, electrolytes, venous or arterial blood gases, AST, and ALT 3
• Assess neurological status, including Glasgow Coma Scale, for signs of encephalopathy 2, 3
• Watch for signs of cerebral edema through clinical assessment or imaging 3

Decision Algorithm Based on Clinical Status

1. If patient has moderate to severe encephalopathy (lethargy, decreased activity, hypotonia, etc.) or rapidly deteriorating neurological status: Initiate both nitrogen scavengers AND CKRT immediately 1
2. If patient is neurologically stable but ammonia level is 200 μmol/L: Start nitrogen scavengers and reassess ammonia level and clinical status in 4 hours 3
3. If ammonia level fails to decrease by 40% within 4-8 hours of nitrogen scavenger therapy: Add CKRT 3

Common Pitfalls and Caveats

• Delayed recognition and treatment can lead to irreversible neurological damage; treat promptly 2, 6
• 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, 2
• Protein restriction should not be prolonged beyond 48 hours to avoid catabolism; reintroduce protein when ammonia levels return to 80-100 μmol/L 1
• Nitrogen scavengers will be dialyzed during CKRT but can still be effective when used concurrently 1
• Monitor for electrolyte disturbances during CKRT, particularly when using high-dose regimens 1, 5

Remember that ammonia levels ≥200 μmol/L represent a threshold above which mortality increases significantly, making aggressive treatment essential 4.