What is a hyperammonemia level in a blood test?

Hyperammonemia Thresholds and Clinical Significance

Ammonia levels above 50 μmol/L (85 μg/dL) in term infants, children, and adults are considered hyperammonemia, with levels ≥200 μmol/L (341 μg/dL) representing a critical threshold associated with significantly increased mortality risk and poor neurological outcomes. 1, 2

Normal Reference Ranges by Age

The definition of "too high" depends on age:

• Adults: Normal is ≤35 μmol/L (≤60 μg/dL); hyperammonemia is ≥50 μmol/L (85 μg/dL) 1
• Neonates (1-7 days): Normal is ≤110 μmol/L (≤154 μg/dL); hyperammonemia is >100 μmol/L (170 μg/dL) 1, 3
• Infants (8-14 days): Normal is <90 μmol/L (≤126 μg/dL) 1
• 15 days to adulthood: Normal is 16-53 μmol/L (22-74 μg/dL) 1

Critical Thresholds for Treatment Decisions

The most clinically important threshold is 200 μmol/L, which represents a point where mortality risk increases significantly and aggressive intervention becomes necessary:

• ≥150 μmol/L: Initiate pharmacological therapy with nitrogen scavengers (sodium benzoate, sodium phenylacetate); consider kidney replacement therapy if neurological deterioration, coma, or cerebral edema present 4
• ≥200 μmol/L: Independent risk factor for mortality; strongly consider continuous kidney replacement therapy (CKRT), especially with encephalopathy 5, 2
• 300-400 μmol/L: Initiate CKRT if levels persist despite medical therapy 5, 4
• >400 μmol/L (681 μg/dL): Severe hyperammonemia requiring immediate kidney replacement therapy 1
• >1,000 μmol/L: Extremely poor prognosis; high-dose CKRT or intermittent hemodialysis mandatory 5, 4

Risk Stratification Based on Ammonia Levels

The risk of mortality increases in a dose-dependent manner within the first 48 hours 2:

• >100 μmol/L: Odds ratio for mortality 1.5 2
• >150 μmol/L: Odds ratio for mortality 1.9 2
• >200 μmol/L: Odds ratio for mortality 3.3 2
• >300 μmol/L: Odds ratio for mortality 2.4 2

Peak ammonia ≥200 μmol/L within the first 48 hours is an independent risk factor for 28-day mortality, with particularly high risk in liver failure patients compared to urea cycle defects. 2

Clinical Symptoms by Severity

Symptoms progress as ammonia levels rise 4:

• Early signs: Lethargy, somnolence 4
• Progressive symptoms: Hyperventilation with respiratory alkalosis, disorientation 4
• Severe manifestations: Coma, cerebral edema, irreversible brain damage 4

Critical Pitfalls in Sample Collection

False elevations are extremely common and can lead to inappropriate aggressive treatment. Proper technique is essential 1:

• Collect from free-flowing venous or arterial blood (no tourniquet, no fist clenching) 1
• Use lithium heparin or EDTA tubes 1
• Transport on ice immediately 1
• Process within 15 minutes of collection 5, 1
• Hemolysis falsely elevates results 1
• Delayed processing causes falsely elevated levels 1

Treatment Algorithm Based on Ammonia Level

For levels 150-200 μmol/L without severe symptoms 4:

• Stop protein intake immediately 5
• Administer IV glucose 8-10 mg/kg/min 5
• Provide IV lipids 0.5-3 g/kg daily 5
• Start nitrogen scavengers (IV sodium benzoate/phenylacetate) 4
• Monitor ammonia every 3-4 hours 5

For levels ≥200 μmol/L or any level with encephalopathy 5, 4:

• All of the above PLUS
• Initiate continuous kidney replacement therapy (CVVHD preferred) 5
• Continue CKRT until ammonia <200 μmol/L on two consecutive hourly measurements 5

For levels >300-400 μmol/L despite medical therapy 5:

• High-dose CKRT mandatory 5
• Consider intermittent hemodialysis for most rapid clearance (75% reduction in 3-4 hours) 5

Prognostic Factors

Poor outcomes are associated with 4:

• Hyperammonemic coma duration >3 days 4
• Plasma ammonia >1,000 μmol/L 4
• Increased intracranial pressure 4

Delayed recognition and treatment lead to irreversible neurological damage; prompt treatment is imperative to optimize outcomes. 4