What is the difference between arterial ammonia and venous ammonia in clinical practice?

Arterial vs Venous Ammonia: Clinical Differences

In clinical practice, venous ammonia sampling is adequate and preferred over arterial sampling, as both correlate similarly with hepatic encephalopathy severity and venous sampling is less invasive. 1

Key Physiological Differences

Arterial ammonia represents the ammonia concentration delivered to tissues, including the brain, while venous ammonia reflects ammonia after tissue extraction and metabolism. 2 Despite this theoretical difference, the clinical utility of arterial versus venous sampling is minimal in most situations.

Correlation with Hepatic Encephalopathy

• Both arterial and venous total ammonia levels correlate significantly with hepatic encephalopathy severity, with arterial showing only marginally better correlation (r=0.61 vs r=0.56, respectively). 1
• The partial pressure of ammonia gas (pNH₃) calculated from arterial blood shows stronger correlation with clinical HE grade (r=0.79) and electrophysiological abnormalities (r=0.71) compared to total arterial ammonia. 3
• However, venous partial pressure of ammonia also correlates well (r=0.52) with HE severity, making the additional invasiveness of arterial sampling unnecessary for routine clinical use. 1

Clinical Practice Recommendations

When to Use Venous Ammonia

• Venous blood ammonia is the standard sampling method for routine clinical assessment of patients with suspected hepatic encephalopathy. 4, 1
• Venous sampling is adequate for diagnostic purposes and monitoring treatment response. 1
• The normal range varies depending on the specific measurement method used, so appropriate reference values must be applied. 4

When Arterial Sampling May Be Considered

• Arterial ammonia measurement may be theoretically superior when precise assessment of ammonia delivery to the brain is needed, as arterial pNH₃ is thought to be more closely related to blood-brain barrier ammonia concentration. 4
• In research settings evaluating the pathophysiology of hepatic encephalopathy, arterial pNH₃ provides better correlation with neurophysiological test results. 3
• However, additional studies are needed to determine the clinical usefulness of arterial pNH₃ measurements in routine practice. 4

Important Clinical Caveats

Limitations of Ammonia Measurements

• Venous blood ammonia levels are not proportional to the degree of HE and have no association with prognosis. 4
• Ammonia metabolism is influenced by multiple organs (kidneys, muscles, brain, bowel) beyond just the liver, limiting the specificity of ammonia measurements. 4
• Patients without hepatic encephalopathy and even those without liver disease can display hyperammonemia. 4
• Ammonia may remain elevated after clinical HE resolution. 4

Critical Diagnostic Value

• A normal ammonia level has high negative predictive value - if a patient with cirrhosis and delirium has normal ammonia, this should prompt investigation for other causes of encephalopathy. 4
• Normal ammonia in suspected HE requires differentiation from other diseases causing cognitive impairment. 4

Prognostic Thresholds

• Arterial ammonia >100 μmol/L predicts severe HE development with 70% accuracy. 5
• Arterial ammonia >200 μmol/L is associated with intracranial hypertension in 55% of acute liver failure patients and correlates with poor neurological outcomes. 6, 5

Practical Algorithm

For routine clinical practice:

1. Use venous ammonia sampling for all diagnostic and monitoring purposes. 1
2. If ammonia is normal in a patient with suspected HE, pursue alternative diagnoses aggressively. 4
3. Reserve arterial sampling only for research protocols or when calculating pNH₃ for specific pathophysiological studies. 3
4. Monitor serial ammonia levels to assess treatment response, not to grade HE severity. 4