What is the treatment for hyperammonemia with an ammonia level of 239?

Treatment of Hyperammonemia with Ammonia Level of 239 μmol/L

For an ammonia level of 239 μmol/L (approximately 407 μg/dL), initiate immediate medical management with nitrogen scavengers and strongly consider continuous kidney replacement therapy (CKRT), as this level approaches the threshold where dialysis becomes critical to prevent irreversible neurological damage. 1

Immediate Stabilization and Initial Medical Management

Stop all protein intake immediately to halt further ammonia production and prevent worsening hyperammonemia. 2, 3

Metabolic Support

• Establish intravenous access and begin glucose infusion at 8-10 mg/kg/min to prevent catabolism, which would generate additional ammonia from protein breakdown. 2, 3
• Provide intravenous lipids starting at 0.5 g/kg daily, up to 3 g/kg daily for adequate caloric support. 2, 3
• Target total caloric intake of ≥100 kcal/kg daily to prevent endogenous protein catabolism. 2, 1
• Critical pitfall: Do not extend protein restriction beyond 48 hours, as prolonged restriction paradoxically increases catabolism and ammonia production. 2, 4

Sample Collection Protocol

• Collect ammonia samples from free-flowing venous or arterial blood (never from a tourniquet-occluded site), transport on ice, and process within 15 minutes to avoid falsely elevated results. 2, 3, 4

Pharmacological Therapy: Nitrogen Scavengers

Initiate nitrogen-scavenging agents immediately as they provide alternative pathways for nitrogen excretion, bypassing the defective urea cycle. 2, 3, 5

Dosing Regimen

For patients <20 kg body weight: 2, 5

• Sodium benzoate: 250 mg/kg as loading dose over 90-120 minutes, then same dose as maintenance over 24 hours
• Sodium phenylacetate: 250 mg/kg as loading dose over 90-120 minutes, then same dose as maintenance over 24 hours
• L-arginine hydrochloride: 200 mg/kg for OTC/CPS deficiencies OR 600 mg/kg for ASS/ASL deficiencies, given over 90 minutes then as maintenance over 24 hours

For patients >20 kg body weight: 2, 5

• Sodium benzoate: 5.5 g/m² as loading dose over 90-120 minutes, then same dose as maintenance over 24 hours
• Sodium phenylacetate: 5.5 g/m² as loading dose over 90-120 minutes, then same dose as maintenance over 24 hours
• L-arginine hydrochloride: 4 g/m² for OTC/CPS deficiencies OR 12 g/m² for ASS/ASL deficiencies

Administration warning: These agents must be diluted and given via central venous catheter to avoid burns from peripheral administration. 5

Kidney Replacement Therapy Decision

At an ammonia level of 239 μmol/L, CKRT should be strongly considered, particularly if there is any evidence of encephalopathy or if ammonia levels continue rising despite medical therapy. 1, 3

Indications for Immediate CKRT

The threshold for initiating dialysis is >300-400 μmol/L despite medical therapy, but your patient at 239 μmol/L is approaching this level and warrants close monitoring with a low threshold for intervention. 2, 3, 4

Initiate CKRT immediately if any of the following develop: 2

• Rapidly deteriorating neurological status or coma
• Cerebral edema on imaging
• Ammonia level rising to >300 μmol/L despite nitrogen scavengers
• Moderate to severe encephalopathy (lethargy, decreased activity, abnormal reflexes)

Preferred CKRT Modality

High-dose continuous venovenous hemodialysis (CVVHD) is the first-line dialysis modality when available, as it provides steady ammonia clearance while maintaining hemodynamic stability. 1, 3

Technical parameters for CVVHD: 1

• Blood flow rate (Qb): 30-50 mL/min
• Dialysate flow rate (Qd): maintain Qd/Qb ratio >1.5
• Warm the dialysate to maintain hemodynamic stability
• Continue until ammonia <200 μmol/L on at least two consecutive hourly measurements

Alternative: Intermittent Hemodialysis

Intermittent HD can reduce ammonia by 50% within 1-2 hours and is indicated when rapid clearance is needed, but carries risk of rebound hyperammonemia and hemodynamic instability. 2, 1, 3

Important consideration: Nitrogen scavengers will be partially removed during dialysis but remain effective when used concurrently, so continue them during CKRT. 1, 3

Monitoring Protocol

Check plasma ammonia levels every 3-4 hours until normalized to assess treatment response and guide therapy adjustments. 1, 3, 4

Assess neurological status continuously using Glasgow Coma Scale and monitor for signs of encephalopathy including lethargy, seizures, abnormal breathing patterns, or altered consciousness. 1, 3

Monitor additional parameters: 5

• Blood glucose and electrolytes (especially during CKRT)
• Venous or arterial blood gases
• Liver function tests (AST, ALT)
• Plasma glutamine and quantitative amino acids

Protein Reintroduction

Reintroduce protein within 48 hours once ammonia levels decrease to 80-100 μmol/L to prevent catabolism. 2, 4

Reintroduction protocol: 2, 3

• Start with 0.25 g/kg daily
• Gradually increase by 0.25 g/kg daily increments
• Target 1.5 g/kg daily as tolerated

Critical Prognostic Factors

The duration of hyperammonemic coma is the most important determinant of neurological outcome, not the rate of ammonia clearance—emphasizing the need for immediate treatment. 3

Adverse prognostic indicators include: 2

• Hyperammonemic coma lasting >3 days
• Increased intracranial pressure
• Peak ammonia level >1,000 μmol/L (1,703 μg/dL)

At your patient's current level of 239 μmol/L, prompt aggressive treatment can prevent progression to these poor prognostic thresholds. 2, 1