What are the next steps in evaluating elevated ammonia levels in a patient with Altered Mental Status (AMS) and no history of liver disease?

From the Guidelines

In a patient with altered mental status (AMS) and elevated ammonia without known liver disease, a thorough workup is essential, including confirmation of elevated ammonia levels and simultaneous initiation of treatment with lactulose and rifaximin, as well as comprehensive laboratory testing and imaging to rule out structural causes and occult liver disease. The next steps in evaluating elevated ammonia levels in such a patient should prioritize identifying the underlying cause of hyperammonemia, considering that ammonia levels can be elevated in non-hepatic encephalopathy (HE) conditions 1. Basic next steps include comprehensive laboratory testing: complete blood count, comprehensive metabolic panel, liver function tests, coagulation studies, and blood cultures.

Key considerations in the workup include:

• Confirming the elevated ammonia with repeat testing
• Initiating treatment to lower ammonia levels with lactulose (15-30 mL orally every 4-6 hours to achieve 2-3 soft bowel movements daily) and rifaximin (550 mg orally twice daily)
• Imaging, such as a brain CT or MRI, to rule out structural causes of AMS and abdominal imaging to evaluate for occult liver disease
• Additional testing for less common causes of hyperammonemia, including urine organic acids, plasma amino acids, and carnitine levels to identify potential inborn errors of metabolism
• Medication review, as certain medications like valproic acid, carbamazepine, and certain antibiotics can cause hyperammonemia 1

Given the potential for neurotoxicity from hyperammonemia, prompt identification and treatment are critical to prevent permanent neurological damage. Urgent consultation with neurology and hepatology/gastroenterology is warranted to guide further management and to rule out other causes of altered mental status, as outlined in recent clinical practice guidelines 1.

From the FDA Drug Label

For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma. The FDA drug label does not answer the question.

From the Research

Evaluating Elevated Ammonia Levels

In a patient with Altered Mental Status (AMS) and no history of liver disease, the next steps in evaluating elevated ammonia levels involve considering various potential causes.

• The patient's medical history, current medications, and laboratory results should be thoroughly reviewed to identify any potential underlying conditions that may be contributing to the elevated ammonia levels 2, 3, 4.
• It is essential to rule out other potential causes of AMS, such as infection, septic shock, or other metabolic disorders 3, 5.
• If the patient is taking valproate, consideration should be given to the possibility of valproate-induced hyperammonemic encephalopathy, a rare but reversible reaction to valproate 4.
• In cases where liver disease is not present, noncirrhotic hyperammonemia should be considered, which can be due to increased production and/or decreased elimination of ammonia 3.
• The patient's condition should be closely monitored, and treatment should be initiated promptly to reduce ammonia levels and prevent further complications 2, 3, 5, 4.

Potential Treatments

Potential treatments for elevated ammonia levels in patients with AMS and no history of liver disease include:

• Lactulose and rifaximin to reduce ammonia production and absorption in the gastrointestinal tract 2, 4, 6.
• Chemotherapy, in cases where the elevated ammonia levels are associated with multiple myeloma 2.
• Hemodialysis, in severe cases where conventional treatments fail to reduce ammonia levels 3.
• Fluid bolus and maintenance fluid, in cases where dehydration is suspected to be contributing to pseudo-hyperammonemia 5.
• Discontinuation of medications that may be contributing to elevated ammonia levels, such as valproate 4.