What is the treatment for hyperammonemia in an unresponsive patient?

Treatment of Hyperammonemia in an Unresponsive Patient

In an unresponsive patient with hyperammonemia, immediate initiation of continuous kidney replacement therapy (CKRT) along with nitrogen scavenger medications is the most effective treatment approach to rapidly reduce ammonia levels and prevent irreversible neurological damage. 1, 2

Initial Management

• Secure airway, breathing, and circulation as the patient is unresponsive 3
• Immediately discontinue all protein intake to prevent further ammonia production 1, 2
• Provide adequate non-protein calories through intravenous glucose at 8-10 mg/kg/min and lipids to prevent catabolism 1, 3
• Target caloric intake of ≥100 kcal/kg daily to prevent protein breakdown 1, 2
• Collect accurate ammonia samples from free-flowing venous or arterial blood, transported on ice, and processed within 15 minutes to avoid false elevations 1, 3

Pharmacological Therapy

Nitrogen Scavengers

• Administer intravenous sodium benzoate and sodium phenylacetate as a loading dose over 90-120 minutes followed by maintenance infusion 4
• Dosage is weight-dependent:
  • For patients <20 kg: 250 mg/kg of each medication 4
  • For patients >20 kg: 5.5 g/m² of each medication 4

Urea Cycle Intermediates

• Add intravenous L-arginine hydrochloride, especially if urea cycle disorder is suspected 1, 4
  • For OTC and CPS deficiencies: 200 mg/kg 1, 3
  • For ASS and ASL deficiencies: 600 mg/kg 1, 3
• Add L-carnitine (50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg daily) if organic acidemia is suspected 1, 2

Kidney Replacement Therapy

• Initiate CKRT immediately in an unresponsive patient with hyperammonemia 5, 1

• Indications for urgent dialysis include:

  • Ammonia levels >300-400 μmol/L despite medical therapy 5, 2
  • Rapidly deteriorating neurological status or coma 1, 3
  • Persistent high blood ammonia levels >400 μmol/l refractory to medical measures 5

• Hemodialysis is the most effective method for rapidly reducing blood ammonia levels (95-96% filtration fraction) 1, 2

• Continuous venovenous hemodialysis (CVVHD) is preferred for hemodynamically unstable patients 2, 3

• Target blood flow rate of 30-50 ml/min with dialysate flow rate/blood flow rate >1.5 2

• Continue CKRT until ammonia levels are <200 μmol/L on at least two consecutive hourly measurements 2

Hybrid Therapy Options

• For patients with severe hemodynamic instability, consider CKRT with ECMO support, which increases blood volume, enables use of larger cannula, and leads to rapid ammonia clearance 5
• Therapeutic hypothermia combined with KRT may be considered as it slows ammonia production by decreasing metabolism (each 1°C decrease in body temperature reduces basal metabolic rate by 8%) 5

Monitoring During Treatment

• Check plasma ammonia levels every 3-4 hours until normalized 1, 2
• Monitor neurological status, including Glasgow Coma Scale 2, 3
• Monitor electrolytes, blood glucose, arterial blood gases, and liver function tests 1, 4
• Assess for signs of cerebral edema through clinical examination or imaging 2, 4

Reintroduction of Protein

• Gradually reintroduce protein within 48 hours (by 0.25 g/kg daily, up to 1.5 g/kg daily) once ammonia levels decrease to 80-100 μmol/L 1, 3
• Avoid prolonged protein restriction beyond 48 hours to prevent catabolism 1, 2

Common Pitfalls and Caveats

• Delayed recognition and treatment can lead to irreversible neurological damage, including seizures, coma, and death 1, 6
• Nitrogen scavengers will be dialyzed during CKRT but can still be effective when used concurrently 1, 2
• Duration of hyperammonemic coma >3 days and plasma ammonia levels >1,000 μmol/l are poor prognostic factors 3, 7
• Patients with recurrent hyperammonemia should be evaluated for underlying urea cycle disorders, even in adulthood 7, 8
• Sodium benzoate and sodium phenylacetate should be administered via central venous catheter as peripheral administration may cause burns 4