Workup for Hyperammonemia
Immediate Diagnostic Evaluation
Measure plasma ammonia immediately from free-flowing venous or arterial blood, transport on ice, and process within 15 minutes to avoid false elevations. 1, 2
Critical Laboratory Tests
- Obtain plasma ammonia level as the primary diagnostic test—any unexplained encephalopathy or altered consciousness requires urgent ammonia measurement 3
- Measure plasma amino acids (quantitative) to differentiate urea cycle defects from other causes—elevated glutamine suggests urea cycle disorder, while specific amino acid patterns identify the defect type 4, 5
- Check blood glucose to assess for hypoglycemia and guide glucose supplementation 4
- Obtain arterial or venous blood gas to evaluate for metabolic acidosis (suggests organic acidemia) or respiratory alkalosis (suggests hyperammonemia) 4
- Measure electrolytes including bicarbonate to assess acid-base status and guide arginine therapy 4
- Check AST and ALT to evaluate for hepatic dysfunction versus non-hepatic causes 4, 6
Urine Studies
- Collect urine for orotic acid measurement—elevated orotic acid indicates ornithine transcarbamylase (OTC) deficiency, while low/normal suggests carbamyl phosphate synthetase (CPS) deficiency 5
- Measure urine amino acids to identify specific patterns associated with argininosuccinate synthetase (ASS) or argininosuccinate lyase (ASL) deficiency 5
Neurological Assessment
- Assess level of consciousness using Glasgow Coma Scale to quantify encephalopathy severity and guide treatment intensity 7, 4
- Evaluate for signs of cerebral edema including papilledema on fundoscopic exam, as hyperammonemia causes neurotoxic brain swelling 4, 3
- Monitor for seizures, lethargy, disorientation, or coma—these indicate severe hyperammonemia requiring immediate intervention 1, 3
Imaging (When Indicated)
- Obtain CT or MRI of brain if neurological deterioration occurs to assess for cerebral edema and gray/white matter damage 4
Treatment-Guiding Thresholds
- Ammonia >150 μmol/L: Initiate nitrogen-scavenging agents (sodium benzoate/phenylacetate) 1, 2
- Ammonia 200-300 μmol/L: Consider continuous kidney replacement therapy (CKRT), especially with encephalopathy 7
- Ammonia >300-400 μmol/L: Urgent hemodialysis or CKRT indicated despite medical therapy 7, 2, 6
- Ammonia >1,000 μmol/L: High-dose CKRT or intermittent hemodialysis mandatory 7
Monitoring During Workup and Treatment
- Recheck plasma ammonia every 3-4 hours until normalized to guide therapy escalation 1, 7, 2
- Monitor electrolytes frequently, particularly during renal replacement therapy when high-dose regimens cause disturbances 7
- Reassess neurological status continuously for signs of deterioration requiring dialysis 7, 4
Common Pitfalls to Avoid
- Delayed ammonia measurement in unexplained encephalopathy leads to irreversible neurological damage—maintain high index of suspicion 1, 2, 3
- Improper sample handling causes falsely elevated results—must use free-flowing blood, ice transport, and <15 minute processing time 1, 2
- Assuming hepatic cause only—consider non-cirrhotic causes including urea cycle defects, organic acidemias, and sepsis with urea-splitting bacteria 5, 6
- Prolonged protein restriction beyond 48 hours induces catabolism and worsens hyperammonemia—reintroduce at 0.25 g/kg/day when ammonia reaches 80-100 μmol/L 1, 2