Is ammonia level measurement required when managing hepatic (liver) encephalopathy?

From the Guidelines

Ammonia levels are not required for the routine management of hepatic encephalopathy, as stated in the most recent guidelines 1. While elevated ammonia is associated with hepatic encephalopathy, treatment decisions should be based on clinical assessment rather than ammonia levels. The standard treatment approach includes lactulose and rifaximin. Lactulose works by acidifying the colon and trapping ammonia, while rifaximin reduces ammonia-producing gut bacteria.

Key Points to Consider

• Ammonia levels correlate poorly with encephalopathy severity, show significant variability, and do not reliably predict treatment response or outcomes 1.
• Proper specimen handling for ammonia measurement is challenging, as levels can be falsely elevated if the sample is not properly collected, transported on ice, or analyzed promptly.
• Clinical assessment of mental status, asterixis, and response to therapy provides more valuable information for managing hepatic encephalopathy than following ammonia levels.
• The most recent guidelines recommend lactulose as secondary prophylaxis following a first episode of overt HE, and should be titrated to obtain 2-3 bowel movements per day 1.
• Rifaximin as an adjunct to lactulose is recommended as secondary prophylaxis following >1 additional episodes of overt HE within 6 months of the first one 1.

Treatment Approach

• Lactulose: starting at 20-30 g orally 3-4 times per day, with goals to achieve 2-3 bowel movements per day 1.
• Rifaximin: 400 mg three times/day or 550 mg twice/day 1. In patients with delirium/encephalopathy and liver disease, plasma ammonia measurement should be performed, as a normal value brings the diagnosis of HE into question 1. However, ammonia levels should not be used as the sole diagnostic criterion for hepatic encephalopathy. Instead, a comprehensive clinical assessment, including mental status, asterixis, and response to therapy, should guide treatment decisions.

From the FDA Drug Label

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 ammonia level is required when managing hepatic encephalopathy is not directly stated in the provided drug label.

• The label mentions that lactulose therapy reduces blood ammonia levels, but it does not explicitly state that ammonia levels are required for management. 2

From the Research

Ammonia Level in Hepatic Encephalopathy Management

• The management of hepatic encephalopathy involves several steps, including lowering blood ammonia levels 3.
• Ammonia is clearly implicated in the pathogenesis of hepatic encephalopathy, and therapeutic management involves reducing ammonia production and increasing its elimination from the blood and the brain 4, 5.
• Various therapeutic agents are available for the management of hepatic encephalopathy, most of which are directed towards lowering the gut nitrogen load and thus the serum ammonia level 4, 6, 5.
• Reducing ammonia production and increasing its elimination are crucial in the management of hepatic encephalopathy, and several therapies, including lactulose and rifaximin, have been shown to be effective in achieving this goal 6, 7.

Importance of Ammonia Level

• Ammonia is a major neurotoxin implicated in the pathogenesis, progression, and severity of hepatic encephalopathy 5.
• The evidence suggests that monitoring and managing ammonia levels is essential in the treatment of hepatic encephalopathy 3, 4, 6, 5.
• Various studies have demonstrated the importance of reducing ammonia levels in the management of hepatic encephalopathy, and therapies that target ammonia reduction have been shown to be effective in improving outcomes 4, 6, 5, 7.

Therapies Targeting Ammonia Reduction

• Lactulose and rifaximin are commonly used therapies that aim to reduce ammonia production in the gut and increase its elimination from the blood and brain 6, 7.
• Other therapies, such as L-ornithine-L-aspartate and branched-chain amino acids, have also been studied as potential options for reducing ammonia levels in hepatic encephalopathy 6.
• The combination of lactulose and rifaximin has been shown to be more effective than lactulose alone in the treatment of overt hepatic encephalopathy, with significant reductions in mortality and hospital stay 7.