What causes spurious hyperammonemia (elevated ammonia levels)?

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Last updated: February 11, 2025View editorial policy

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From the Guidelines

Spurious hyperammonemia is primarily caused by pre-analytical events.

Factors Contributing to Spurious Hyperammonemia

  • Delayed sample processing: Failing to process samples promptly can lead to anomalous plasma ammonia concentrations 1.
  • Temperature: Not placing the sample on ice can affect the stability of the ammonia molecule and lead to inaccurate measurements 1.
  • Type of test matrices: The choice of anticoagulant, such as heparin, EDTA, or oxalate, can impact ammonia levels, with EDTA-anticoagulated plasma being superior 1.
  • Hemolysis: Hemolysis can cause false elevations in ammonia levels due to the release of intracellular ammonia 1.
  • Storage time in freezer: Extensive freezing or multiple freezing and thawing cycles can significantly affect ammonia levels 1. It is crucial to follow proper handling and storage procedures, such as keeping the sample on ice, removing plasma from cells immediately, and analyzing the sample within 2 hours of sampling, to minimize the risk of spurious hyperammonemia 1.

From the Research

Causes of Spurious Hyperammonemia

  • Pre-analytical conditions, such as capillary samples and delay between sampling and centrifugation, can lead to false positives in plasma ammonia measurement 2
  • The quality of the sample draw, its handling, and preparation for analysis can also cause significant analytical errors in blood ammonia testing 3

Nonhepatic Causes of Hyperammonemia

  • Nonhepatic hyperammonemia can be caused by increased production and/or decreased elimination of ammonia, and can be associated with conditions such as septic shock and urea cycle enzyme deficiencies 4, 5
  • Hyperammonemia can also occur in patients with intact liver function, and prompt treatment should begin with reducing the catabolic state, nitrogen scavenging, replacing urea cycle substrates, decreasing intestinal absorption, and augmented removal of ammonia with renal replacement therapy 5

Hyperammonemia in Convulsive Seizures

  • Hyperammonaemia is frequently observed in patients who have experienced convulsive seizures, and can be associated with factors such as elevated venous lactate, lowered venous pH, sex (male), and longer duration of convulsion 6
  • Excessive skeletal muscle contraction and/or respiratory failure during/after convulsive seizure may be the primary mechanism of hyperammonaemia 6

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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