What is the treatment for metabolic encephalopathy?

From the Guidelines

The treatment for metabolic encephalopathy, specifically hepatic encephalopathy, should prioritize the use of a non-absorbable disaccharide, such as lactulose or lactitol, to prevent recurrence, as recommended by the most recent guidelines 1.

Key Considerations

• The use of lactulose or lactitol is recommended to prevent the recurrence of hepatic encephalopathy in patients with cirrhosis, with a Grade 1+ and Strong Agreement rating 1.
• Rifaximin can be added to prevent recurrence in cases where lactulose or lactitol is not effective, or used alone if lactulose is poorly tolerated, based on expert opinion and strong agreement 1.
• A therapeutic education program should be offered to the patient and caregiver to improve quality of life and limit hospitalizations, also based on expert opinion and strong agreement 1.

Treatment Approach

• Identify and correct the underlying metabolic disturbance, such as treating hyperammonemia with lactulose and rifaximin.
• Restrict protein intake to 0.8-1.0 g/kg/day and administer lactulose to reduce ammonia levels in hepatic encephalopathy.
• Consider the use of rifaximin, particularly in cases where lactulose is not effective or poorly tolerated.
• Supportive measures, including maintaining adequate oxygenation, treating seizures, and managing increased intracranial pressure, are crucial.

Evidence Basis

• The 2023 French recommendations for the diagnosis and management of hepatic encephalopathy provide the most recent and highest-quality evidence for the treatment approach 1.
• While other studies, such as the 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver, and the 2023 guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU, provide additional insights, the French recommendations are the most relevant and up-to-date 1.

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 treatment for metabolic encephalopathy, specifically portal-systemic encephalopathy, is lactulose (PO), which has been shown to reduce blood ammonia levels and improve mental state in about 75% of patients 2.

• The recommended adult oral dosage is 2 to 3 tablespoonfuls (30 mL to 45 mL, containing 20 grams to 30 grams of lactulose) three or four times daily 2.
• Improvement in the patient’s condition may occur within 24 hours but may not begin before 48 hours or even later 2.

From the Research

Treatment Options for Metabolic Encephalopathy

• The treatment of metabolic encephalopathy mainly consists of correcting the underlying cause 3, 4, 5.
• Specific treatment options are available for certain types of metabolic encephalopathy, such as hepatic encephalopathy, which can be treated with non-absorbable disaccharides, rifaximin, or branched-chain amino acids 6.
• Supportive care and management of the underlying etiology are crucial in the treatment of metabolic encephalopathy 4, 5.
• Directed therapies that target neurochemical and neurotransmitter pathways are not currently available and represent an important area for future research 4.

Approaches to Management

• Recognition and treatment of encephalopathy are critical to improving outcomes in critically ill patients 4.
• A diagnostic and therapeutic strategy for the care of patients with metabolic encephalopathy should include the identification of the underlying cause and the implementation of appropriate treatment measures 3.
• The treatment of metabolic encephalopathy should be individualized based on the specific cause and severity of the condition 7.

Reversibility and Outcome

• Most metabolic encephalopathies are reversible unless secondary complications occur 5.
• The severity of encephalopathy generally correlates with that of the systemic illness, and the outcome depends on the underlying cause and the promptness of treatment 3, 5, 7.
• Mortality rates for patients with metabolic encephalopathy can be high, ranging from 16-65% for septic encephalopathy, and one-year survival rates for patients with encephalopathy and liver cirrhosis can be less than 50% 7.