Normal Serum Ammonia Levels
Normal serum ammonia levels vary by age: in adults and children ≥15 days old, the normal range is 16–53 μmol/L (22–74 μg/dL), while neonates have higher thresholds with levels ≤110 μmol/L (154 μg/dL) at 1–7 days and <90 μmol/L (126 μg/dL) at 8–14 days of age. 1, 2
Age-Specific Normal Ranges
The interpretation of ammonia levels is critically age-dependent:
- Adults and children ≥15 days: 16–53 μmol/L (22–74 μg/dL) 2
- Neonates 1–7 days old: ≤110 μmol/L (154 μg/dL) 1, 2
- Infants 8–14 days old: <90 μmol/L (126 μg/dL) 1, 2
- General adult reference: ≤35 μmol/L (≤60 μg/dL) 2, 3
Clinical Thresholds for Hyperammonemia
Understanding when ammonia becomes pathological is essential for clinical decision-making:
- Hyperammonemia definition in neonates: >100 μmol/L (170 μg/dL) 2
- Hyperammonemia definition in term infants, children, and adults: ≥50 μmol/L (85 μg/dL) 2
- Threshold for poor neurological outcomes: >200 μmol/L (341 μg/dL) 2, 4
- Threshold for kidney replacement therapy consideration: >150 μmol/L (255 μg/dL) 1
- Severe hyperammonemia requiring aggressive intervention: >400 μmol/L (681 μg/dL) 2
Research demonstrates that mortality risk increases significantly at ammonia levels ≥200 μmol/L within the first 48 hours, particularly in liver failure patients. 4 In acute liver failure, levels >100 μmol/L predict severe hepatic encephalopathy with 70% accuracy, and intracranial hypertension develops in 55% of patients with levels >200 μmol/L. 5
Critical Sampling Requirements
Ammonia measurement is notoriously prone to pre-analytical errors, making proper collection technique absolutely essential:
- Collect from free-flowing venous or arterial blood without venous stasis (no tourniquet use or fist clenching) 1, 2, 6
- Use lithium heparin or EDTA tubes 1, 2
- Transport on ice immediately to the laboratory 1, 2
- Process within 15 minutes of collection and analyze immediately 1, 2
- Collect from fasting patients when possible 2
- Fill tube completely, secure lid, and homogenize by inversion 2
Common Pitfalls to Avoid
- Hemolysis falsely elevates results 2
- Delayed processing leads to falsely elevated levels as red blood cells continue to produce ammonia 2
- High lipemia and jaundice interfere with measurement 2
- High-protein diet, smoking, exercise, and certain drugs (especially valproic acid) can affect levels 2
- If delayed measurement is unavoidable, centrifuge at +4°C and freeze the supernatant at −70/−80°C 2
Clinical Context and Interpretation
A normal ammonia level essentially rules out hepatic encephalopathy, while elevated levels in cirrhotic patients do not necessarily confirm it, as many cirrhotic patients have chronically elevated ammonia without encephalopathy. 2, 7 However, ammonia levels do correlate with the severity and prognosis of hepatic encephalopathy when present. 2
Elevated ammonia >100 μmol/L combined with family history of liver disease, neurological disorders, or severe neurological impairment should prompt investigation for inherited metabolic disorders such as urea cycle defects. 2