At what ammonia level should treatment be initiated?

Treatment Threshold for Hyperammonemia

Treatment with nitrogen scavengers should be initiated when ammonia levels exceed 150 μmol/L, and continuous kidney replacement therapy (CKRT) should be strongly considered at levels of 200 μmol/L or higher, particularly if encephalopathy is present. 1, 2

Treatment Algorithm Based on Ammonia Levels

Ammonia >150 μmol/L

• Initiate nitrogen scavengers immediately (sodium benzoate and sodium phenylacetate) at this threshold 2
• Stop protein intake completely to prevent further ammonia production 1
• Begin 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 for adequate caloric intake 1
• Target total caloric intake of ≥100 kcal/kg daily 1

Ammonia 200 μmol/L

• Initiate medical management with nitrogen scavengers AND strongly consider CKRT at this level to prevent mortality 1
• The National Kidney Foundation specifically recommends considering CKRT at 200 μmol/L, especially with evidence of encephalopathy 1

Ammonia 300-400 μmol/L

• Hemodialysis is recommended if levels reach this range despite medical therapy, or if neurological status rapidly deteriorates 1, 2, 3
• This threshold represents failure of medical management and requires urgent dialysis 2

Ammonia >1,000 μmol/L

• High-dose CKRT or intermittent hemodialysis should be initiated immediately at these extremely elevated levels 1

Monitoring Treatment Response

Reassessment Criteria

• Check plasma ammonia levels every 3-4 hours until normalized 1, 2, 3
• If ammonia fails to fall below 150 μmol/L or by more than 40% within 4-8 hours after starting nitrogen scavengers, hemodialysis is recommended 4
• Continue CKRT until ammonia levels are <200 μmol/L on at least two consecutive hourly measurements 1

Expected Response

• Mean ammonia concentrations should decrease from approximately 200 μmol/L to around 100 μmol/L within four hours of initiating sodium phenylacetate and sodium benzoate therapy 4
• Hemodialysis can decrease blood ammonia concentrations by 75% within 3-4 hours 1

Critical Caveats

Sample Collection

• 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, 3
• Improper handling is a major source of falsely elevated results 5

Protein Reintroduction

• Protein restriction should not be prolonged beyond 48 hours to avoid catabolism 1, 2, 3
• Reintroduce protein when ammonia levels return to 80-100 μmol/L 1
• Start with 0.25 g/kg/day and gradually increase up to 1.5 g/kg/day as tolerated 2

Neurological Urgency

• For patients with rapidly deteriorating neurological status, coma, or cerebral edema with blood ammonia levels >150 μmol/L, CKRT should be initiated immediately 1
• Delayed recognition and treatment can lead to irreversible neurological damage 1, 2, 3
• Assess neurological status using Glasgow Coma Scale regularly 1, 4

Important Distinction: Hepatic Encephalopathy vs. Metabolic Hyperammonemia

The thresholds above apply primarily to metabolic hyperammonemia (urea cycle disorders, inborn errors of metabolism). For hepatic encephalopathy from cirrhosis, ammonia levels do not correlate well with clinical severity and should not guide lactulose dosing 6, 7. In cirrhotic patients, only 60% with overt hepatic encephalopathy have elevated ammonia levels 6, and treatment decisions should be based on clinical presentation rather than ammonia values 6, 8.