Is it likely that a patient has hepatic encephalopathy due to elevated ammonia levels with normal Blood Urea Nitrogen (BUN)?

From the Guidelines

It is unlikely that a patient has hepatic encephalopathy due to elevated ammonia levels with normal Blood Urea Nitrogen (BUN). Ammonia-related encephalopathy typically occurs in the setting of liver dysfunction or severe portal hypertension, conditions that usually affect both ammonia and BUN metabolism. The liver is responsible for converting ammonia to urea through the urea cycle, and when liver function is compromised, ammonia levels rise while BUN may decrease. Normal BUN suggests intact hepatic synthetic function for urea production. However, there are exceptions where ammonia can be elevated with normal BUN, such as in certain inborn errors of metabolism (like urea cycle disorders), portosystemic shunts, certain medications (valproic acid), or severe muscle exertion. According to the most recent guidelines, a normal blood ammonia level has negative predictive value, and normal ammonia in a patient with cirrhosis and delirium should prompt renewed or further differential diagnostic work-up for other causes of delirium 1. If ammonia-related encephalopathy is suspected despite normal BUN, additional testing should be pursued, including complete liver function tests, imaging studies, and possibly genetic testing for metabolic disorders. Treatment would depend on the underlying cause but often includes reducing ammonia production and enhancing its elimination through medications like lactulose or rifaximin. Key considerations in the diagnosis of hepatic encephalopathy include the clinical presentation, which can range from mild cognitive impairment to coma, and the presence of asterixis, a flapping tremor that is often seen in patients with hepatic encephalopathy 1. In clinical practice, it is essential to consider the patient's overall clinical picture, including liver function, ammonia levels, and other potential causes of encephalopathy, to make an accurate diagnosis and develop an effective treatment plan.

From the FDA Drug Label

For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma. Controlled studies have shown that lactulose solution therapy reduces the blood ammonia levels by 25 to 50%; this is generally paralleled by the improvement in the patients’ mental state and by an improvement in EEG patterns.

The answer to whether it is likely that a patient has hepatic encephalopathy due to elevated ammonia levels with normal Blood Urea Nitrogen (BUN) is yes, as elevated ammonia levels are a key factor in the development of hepatic encephalopathy, and normal BUN does not rule out this condition. Key points to consider include:

• Elevated ammonia levels are a primary cause of hepatic encephalopathy
• Normal BUN does not exclude the diagnosis of hepatic encephalopathy
• Lactulose therapy can reduce blood ammonia levels and improve mental state in patients with hepatic encephalopathy 2

From the Research

Hepatic Encephalopathy and Ammonia Levels

• Hepatic encephalopathy is thought to be central in the pathophysiology of liver failure, with hyperammonemia playing a key role 3.
• Elevated ammonia levels can be associated with hepatic encephalopathy, even in the absence of liver disease, as seen in cases of multiple myeloma 4.
• However, ammonia levels do not always guide clinical management of patients with hepatic encephalopathy caused by cirrhosis, with no significant differences in lactulose dose between patients with normal or elevated ammonia levels 5.

Normal Blood Urea Nitrogen (BUN) and Hepatic Encephalopathy

• There is no direct evidence to suggest that a patient with normal BUN and elevated ammonia levels is likely to have hepatic encephalopathy.
• However, it is possible for patients with normal liver function to experience hyperammonemic encephalopathy, as seen in cases of valproic acid-induced hyperammonemic encephalopathy 6.
• In some cases, hyperammonemia may be caused by dehydration-associated pseudo-hyperammonemia, which can be resolved with fluid bolus and maintenance fluid without requiring lactulose or rifaximin 7.

Diagnosis and Treatment

• Clinicians should be aware of the potential for hyperammonemic encephalopathy in patients presenting with altered mental status, particularly in cases where other potential causes have been ruled out 4.
• Treatment for hyperammonemic encephalopathy may involve lactulose, rifaximin, or other medications, depending on the underlying cause of the condition 3, 4, 6.