What are the treatment options for a patient with hyperammonemia (elevated ammonia level of 239)?

Management of Ammonia Level 239 μmol/L (407 μg/dL)

This ammonia level of 239 μmol/L requires immediate aggressive medical management with nitrogen scavengers, caloric support, and protein restriction, but does NOT yet meet the threshold for urgent dialysis unless neurological deterioration occurs. 1, 2

Immediate Actions (Within Minutes)

Stop All Protein Intake

• Discontinue all oral feeds and protein intake immediately to halt nitrogen load and prevent further ammonia production 2, 3, 4
• This is the single most critical first step in management 2

Secure Airway and Assess Neurological Status

• Intubate if neurological status is deteriorating, coma developing, or signs of cerebral edema present 2, 3
• Assess for moderate encephalopathy (lethargy, hypotonia, weak suck, constricted pupils, bradycardia) or severe encephalopathy (stupor, coma, decerebrate posture, flaccid tone, pupils non-reactive) 1
• The duration of hyperammonemic coma is the most important prognostic factor—not the rate of ammonia clearance 1, 4

Aggressive Caloric Support (First Hour)

Prevent Catabolism

• Provide ≥100 kcal/kg/day through IV dextrose and lipids to prevent protein breakdown, which worsens hyperammonemia 1, 2, 3, 4
• Maintain glucose infusion rate at 8-10 mg/kg/min 1, 2, 4
• Start IV lipids at 0.5 g/kg/day, titrating up to 3 g/kg/day for additional calories 1, 2, 4
• Protein catabolism will drive further ammonia production if adequate calories are not provided 1

Pharmacological Therapy (Within 1-2 Hours)

Nitrogen-Scavenging Agents

Initiate IV sodium benzoate and sodium phenylacetate immediately 1, 2, 4, 5:

For patients <20 kg body weight:

• Sodium benzoate: 250 mg/kg IV over 90-120 minutes as loading dose, then same dose over 24 hours as maintenance 1, 5
• Sodium phenylacetate: 250 mg/kg IV over 90-120 minutes as loading dose, then same dose over 24 hours as maintenance 1, 5

For patients >20 kg body weight:

• Sodium benzoate: 5.5 g/m² IV over 90-120 minutes as loading dose, then same dose over 24 hours as maintenance 1, 5
• Sodium phenylacetate: 5.5 g/m² IV over 90-120 minutes as loading dose, then same dose over 24 hours as maintenance 1, 5

Critical caveat: Maximum dose of sodium benzoate is 12 g daily—high-dose benzoate can be toxic and lethal within 1 hour 1

Urea Cycle Intermediates

Administer IV L-arginine hydrochloride (dosing depends on specific enzyme deficiency if known) 1, 4:

• For OTC and CPS deficiencies: 200 mg/kg (if <20 kg) or 4 g/m² (if >20 kg) over 90 minutes, then as maintenance over 24 hours 1
• For ASS and ASL deficiencies: 600 mg/kg (if <20 kg) or 12 g/m² (if >20 kg) over 90 minutes, then as maintenance over 24 hours 1

Monitor for hyperchloremic acidosis with high-dose arginine and administer bicarbonate as needed 5

L-Carnitine (If Organic Acidemia Suspected)

• 50 mg/kg loading dose over 90 minutes, then 100-300 mg/kg daily 1, 2, 4
• Not needed for urea cycle disorders but essential for organic acidurias 1

Protein Reintroduction (Within 48 Hours)

• Gradually reintroduce protein within 48 hours once ammonia decreases to 80-100 μmol/L 1, 3, 4
• Start at 0.25 g/kg/day and increase up to 1.5 g/kg/day 1, 3, 4
• Do not prolong protein restriction beyond 48 hours—this causes protein catabolism which drives further ammonia production 1, 4

Dialysis Decision Algorithm

At ammonia level 239 μmol/L (407 μg/dL), dialysis is NOT yet indicated UNLESS:

Absolute Indications for Immediate Dialysis 1, 2, 4:

• Rapidly deteriorating neurological status, coma, or cerebral edema with ammonia >150 μmol/L (256 μg/dL) 1
• Moderate or severe encephalopathy (as defined above) 1
• Persistently high ammonia >400 μmol/L (681 μg/dL) refractory to medical measures 1
• Rapid rise to >300 μmol/L (511 μg/dL) within a few hours that cannot be controlled with medical therapy 1

Dialysis Modality Selection 1, 2, 4:

• High-dose continuous venovenous hemodialysis (CVVHD) is first-line when available: blood flow rate 30-50 mL/min with dialysis fluid flow rate/Qb ratio >1.5 1, 4
• Intermittent hemodialysis is alternative: achieves 50% ammonia reduction within 1-3 hours with 95-96% filtration fraction, but carries risk of post-dialytic rebound 2, 4
• Peritoneal dialysis is significantly less effective and only recommended when HD or CKRT unavailable 1, 2
• Nitrogen scavengers remain effective during dialysis and should be continued concurrently despite being dialyzed 2, 4

Monitoring Protocol

Ammonia Levels

• Check plasma ammonia every 3-4 hours until normalized 2, 3, 4
• Samples must be collected from free-flowing venous or arterial blood, transported on ice, and processed within 15 minutes to avoid false elevations 3, 4

Additional Monitoring 5:

• Glutamine and quantitative plasma amino acids
• Blood glucose and electrolytes (especially during CKRT)
• Venous or arterial blood gases
• AST and ALT
• Neurological status and Glasgow Coma Scale
• CT/MRI for cerebral edema if neurological deterioration occurs

Underlying Etiology Investigation

While treating, investigate cause 2:

• Urea cycle disorders (OTC, CPS, ASS, ASL, ARG deficiencies)
• Organic acidemias (propionic acidemia, methylmalonic acidemia)
• Transient hyperammonemia of the newborn
• Severe liver failure
• Medications (valproate, chemotherapy)
• Infections with urea-metabolizing organisms

Critical Pitfalls to Avoid

• Delayed treatment is the most important prognostic factor—duration of hyperammonemic coma determines survival and neurological outcome, not the rate of ammonia clearance 1, 4, 6
• Do not repeat loading doses of sodium phenylacetate/benzoate due to prolonged plasma levels and risk of toxicity 5
• Do not use peripheral IV for nitrogen scavengers—must use central venous catheter to avoid burns 5
• Do not prolong protein restriction beyond 48 hours without reintroduction 1, 4
• Ammonia levels do not guide lactulose dosing in hepatic encephalopathy from cirrhosis (different pathophysiology) 7