Ammonia Trending in Hepatic Encephalopathy
No, you should not trend ammonia levels to guide clinical management or monitor treatment response in patients with hepatic encephalopathy.
Initial Diagnostic Role Only
The primary utility of ammonia measurement is limited to the initial diagnostic evaluation when HE is suspected:
A normal ammonia level should prompt you to question the diagnosis of HE and search for alternative causes of altered mental status 1. This is the most important clinical application of ammonia testing.
If ammonia is checked in a patient with suspected overt HE and returns normal, the diagnosis of HE is in doubt and requires diagnostic reevaluation 1.
The AASLD/EASL guidelines explicitly state that increased blood ammonia alone does not add any diagnostic, staging, or prognostic value for HE in patients with chronic liver disease 1.
Why Serial Ammonia Levels Are Not Useful
Multiple lines of evidence demonstrate that trending ammonia provides no clinical benefit:
Ammonia levels do not correlate with treatment response or guide lactulose dosing in clinical practice 2. A large study of 1,202 HE admissions found no correlation between lactulose dose and ammonia level (R = 0.0026), and patients received identical lactulose doses regardless of whether ammonia was elevated or normal 2.
There was no correlation between time to OHE resolution and ammonia levels 3. Ammonia measurement did not impact clinical decision-making or patient outcomes 4.
While some older studies showed correlation between ammonia levels and HE severity at a single time point 5, 6, this does not translate to clinical utility for serial monitoring, as HE is diagnosed and graded by clinical criteria using the West Haven Criteria and Glasgow Coma Scale 1.
The One Exception: Testing Ammonia-Lowering Drug Efficacy
The guidelines acknowledge a narrow exception:
For ammonia-lowering drugs specifically, repeated measurements of ammonia may be helpful to test drug efficacy 1. However, this refers to research or pharmacologic evaluation contexts, not routine clinical management.
Lactulose therapy reduces blood ammonia levels by 25-50%, generally paralleled by improvement in mental state 7, but clinical response—not ammonia levels—should guide your dosing (titrate to 2-3 soft stools daily).
Critical Measurement Considerations
If you do check ammonia, proper technique is essential to avoid false elevations:
Collect from fasting patients when possible, avoiding venous stasis (no tourniquet or fist clenching) 1, 8.
Use EDTA-containing tubes, place immediately on ice, and transport to laboratory within 60-90 minutes 1, 8.
Sample hemolysis, high lipemia, jaundice, high-protein diet, smoking, and exercise can all interfere with results 1, 8.
Common Pitfalls to Avoid
Do not use ammonia levels to determine HE severity or grade—this is done clinically 1.
Do not adjust lactulose dosing based on ammonia levels—dose to clinical response (2-3 soft stools daily) 2, 4.
Do not repeat ammonia levels to assess treatment response—assess mental status clinically 2, 4, 3.
Do not assume elevated ammonia confirms HE—ammonia may be elevated in cirrhotic patients without any encephalopathy 1, 8. Only 60% of patients with confirmed overt HE have elevated ammonia levels 2.
Do investigate alternative diagnoses when ammonia is normal—including infections, metabolic derangements, intracranial hemorrhage, drug effects, and alcohol withdrawal 9.