What is the management for hyperammonemia (elevated ammonia)?

Management of Elevated Ammonia (Hyperammonemia)

Immediately initiate treatment without delay when hyperammonemia is detected, as coma duration and ammonia peak levels directly correlate with irreversible neurological damage and death. 1, 2

Immediate Stabilization and Initial Actions

Stop all protein intake immediately to halt nitrogen load and prevent further ammonia production. 1, 3

• Secure airway, breathing, and circulation—intubate if neurological status is deteriorating. 3, 4
• Establish central venous access (peripheral IV may cause burns with concentrated nitrogen scavengers). 5
• Begin aggressive caloric support to prevent catabolism, which worsens hyperammonemia. 1, 3

Caloric Support Protocol

• Provide ≥100 kcal/kg/day through IV dextrose and lipids. 1, 4
• Maintain glucose infusion rate at 8-10 mg/kg/min to prevent protein breakdown. 1, 5
• Start IV lipids at 0.5 g/kg/day, titrating up to 3 g/kg/day for additional calories. 1, 4
• Reintroduce protein within 48 hours (starting at 0.25 g/kg/day, increasing to 1.5 g/kg/day) once ammonia decreases to 80-100 μmol/L—prolonged protein restriction causes catabolism. 1, 3

Pharmacological Therapy

Nitrogen Scavengers (Initiate if ammonia >150 μmol/L)

Administer sodium phenylacetate and sodium benzoate as a loading dose over 90-120 minutes, followed by continuous 24-hour maintenance infusion. 1, 5

Dosing (body weight-dependent): 1, 5

• Patients <20 kg: 250 mg/kg each of sodium phenylacetate and sodium benzoate
• Patients >20 kg: 5.5 g/m² each of sodium phenylacetate and sodium benzoate

Must dilute with sterile 10% dextrose before administration via central line. 5

Arginine Supplementation (Urea Cycle Disorder-Specific)

Administer IV L-arginine hydrochloride based on the specific enzyme deficiency: 1, 5

• OTC and CPS deficiencies: 200 mg/kg
• ASS and ASL deficiencies: 600 mg/kg

Additional Medications

• L-carnitine: 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg/day for organic acidemias. 1
• Antiemetics during nitrogen scavenger infusion to control nausea/vomiting. 5

Kidney Replacement Therapy (KRT)

Initiate hemodialysis or continuous kidney replacement therapy (CKRT) when ammonia levels exceed 300-400 μmol/L despite medical therapy, or with rapidly deteriorating neurological status or coma. 1, 3, 4

KRT Modality Selection

• Hemodialysis is the most effective method with 95-96% ammonia filtration fraction and provides the fastest ammonia reduction. 1
• CKRT is preferred for hemodynamically unstable patients and can be combined with ECMO support if needed. 1
• Peritoneal dialysis is significantly less effective than HD or CKRT. 1
• Nitrogen scavengers remain effective during dialysis and should be continued concurrently despite being dialyzed. 1

Adjunctive Therapies During KRT

• Therapeutic hypothermia may be considered—each 1°C decrease in body temperature reduces basal metabolic rate by 8%, slowing ammonia production. 1

Monitoring Protocol

Check plasma ammonia levels every 3-4 hours until normalized. 1, 3, 4

• Assess neurological status continuously using Glasgow Coma Scale. 5
• Monitor electrolytes closely, especially during CKRT. 1, 4
• Track blood glucose, venous/arterial blood gases, AST, ALT, and quantitative plasma amino acids. 5
• Consider transcranial Doppler ultrasound in severe coma to monitor cerebral blood flow and detect cerebral edema. 2

Critical Pitfalls to Avoid

Ammonia samples must be collected from free-flowing venous or arterial blood, transported on ice, and processed within 15 minutes—improper handling causes falsely elevated results. 1, 3, 4

• Never delay treatment waiting for confirmatory testing—irreversible brain damage occurs rapidly. 1, 3
• Do not restrict protein beyond 48 hours—this triggers catabolism and worsens hyperammonemia. 1, 4
• Do not administer repeat loading doses of nitrogen scavengers—phenylacetate has prolonged plasma levels and repeat loading is contraindicated. 5
• Avoid peripheral IV administration of concentrated nitrogen scavengers—this causes burns. 5

Underlying Cause Investigation

While treatment proceeds, investigate the etiology: 6, 2, 7

• Urea cycle disorders (most common in neonates/infants)
• Organic acidemias
• Severe liver failure
• Medications (valproate, chemotherapy)
• Transient hyperammonemia of the newborn (usually self-limited in preterm neonates)