Do you have to check an ammonia level if you’re concerned about encephalopathy?

Sometimes, you might be told to order a serum ammonia level on a patient who is encephalopathic, whether they have a history of liver disease or not. Why? Does the ammonia level actually matter?

I would argue for most cases, no. There are specific situations in which serum ammonia is a good prognostic or diagnostic test:

  • Acute liver failure (or acute fatty liver of pregnancy)–associated with risk of cerebral herniation and poorer outcomes
  • Patients who have inborn errors of metabolism–can suggest a diagnosis of urea cycle disorders
  • Reyes syndrome–can be suggestive of this diagnosis
  • Monitoring of ammonia-lowering therapy–in the research phase as far as I know

If you have a patient with cirrhosis or chronic liver disease who comes in with hepatic encephalopathy, though, the serum ammonia level is almost certainly not going to change your management. Ask yourself: If the ammonia level is 20 in a patient with major hand flapping, will you stop their lactulose? If it’s 140 in an alert cirrhotic will you get a head CT to look for cerebral herniation? Probably no, and no. It’s generally agreed that a serum ammonia level >100 is probably bad. And then there’s the question of arterial, venous, or partial pressure–better to just not get it in the first place. It also costs anywhere from $30-50.

Study results vary on whether the serum ammonia level is correlated with encephalopathy. For example, this study of about 120 patients suggests that it is, whereas this study of about 20 patients suggests not,  and this study says yes for ALF but not for patients with chronic liver disease. Even if the majority of evidence tips (pun not intended) towards ammonia levels and encephalopathy being correlated, no one has been able to define specific numerical cut-offs for what levels correlate with mild, moderate, or severe hepatic encephalopathy. So ammonia levels remain clinically not useful for managing most cases of hepatic encephalopathy. I rest my case with this clinical vignette and discussion by Phillip Ge and Bruce Runyon.

NB: I recommend this comprehensive review of the physiology of ammonia: it covers where and how ammonia is made, and how ammonia acts as a neurotoxin in the body. I can honestly say it was the first time I enjoyed reading about glutaminases.

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