What is the management of encephalopathy?

From the Guidelines

The primary treatment for hepatic encephalopathy is lactulose, which should be administered orally at a dose of 20-30 g, 3-4 times per day, with the goal of achieving 2-3 soft stools per day, as recommended by the most recent guidelines 1.

Key Considerations

• The dose of lactulose should be titrated to achieve the desired stool frequency, and if patients are unable to take medications orally, administration via nasogastric tube may be considered 1.
• For severe cases, an enema with lactulose 200 g and 700 mL water may be performed 3-4 times per day 1.
• Rifaximin, at a dose of 400 mg three times per day or 550 mg twice per day, may be added for recurrent episodes of hepatic encephalopathy, as suggested by recent studies 1.

Additional Therapies

• Other pharmacological options for managing overt hepatic encephalopathy include oral branched-chain amino acids (BCAA) at a dose of 0.25 g/kg/day, intravenous L-ornithine-L-aspartate (LOLA) at a dose of 30 g/day, and albumin at a dose of 1.5 g/kg/day until clinical improvement or for a maximum of 10 days 1.
• Polyethylene glycol may be used as a substitute for non-absorbable disaccharides, with a dose of 4 liters orally 1.

Important Notes

• Neomycin and metronidazole are not recommended for the management of hepatic encephalopathy due to their potential side effects, such as intestinal malabsorption, nephrotoxicity, and ototoxicity 1.
• Early identification and treatment of precipitating factors, such as gastrointestinal bleeding, infection, constipation, and dehydration, are crucial in the management of hepatic encephalopathy, as outlined in recent 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. 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 clinical response has been observed in about 75% of patients, which is at least as satisfactory as that resulting from neomycin therapy. In the treatment of chronic portal-systemic encephalopathy, lactulose has been given for over 2 years in controlled studies.

Encephalopathy Management: Lactulose is used for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma.

• The goal of treatment is to reduce blood ammonia levels and improve the patient's mental state.
• Treatment Outcomes: Clinical response is observed in about 75% of patients, with improvement in mental state and EEG patterns.
• Duration of Therapy: Continuous long-term therapy is indicated to lessen the severity and prevent the recurrence of portal-systemic encephalopathy 2.

The usual 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. Hourly doses of 30 mL to 45 mL of lactulose solution may be used to induce the rapid laxation indicated in the initial phase of the therapy of portal-systemic encephalopathy. Improvement in the patient’s condition may occur within 24 hours but may not begin before 48 hours or even later.

• Dosage and Administration: The usual adult oral dosage is 2 to 3 tablespoonfuls (30 mL to 45 mL) three or four times daily, with adjustments as needed to produce 2 or 3 soft stools daily 2.

From the Research

Encephalopathy Management

• Hepatic encephalopathy (HE) is a reversible decrease in neurologic function caused by liver disease, and treatment has traditionally been with non-absorbable disaccharides along with antibiotics and supportive measures 3.
• The use of lactulose and rifaximin in the management of HE has been studied, with some studies suggesting that lactulose is effective for the prevention of overt HE recurrence over the long term, and that the addition of rifaximin to lactulose significantly reduces the risk of overt HE recurrence and HE-related hospitalization 4.
• A study comparing the efficacy of rifaximin versus lactulose for reducing the recurrence of overt HE and hospitalizations in cirrhosis found that rifaximin and lactulose are equally effective for the maintenance of remission from overt HE, but rifaximin is superior for reducing the risk of HE-related hospitalization 5.

Treatment Options

• Lactulose is recommended as a first-line therapy in overt hepatic encephalopathy (OHE) 3.
• The combination of lactulose and rifaximin is more effective than lactulose alone in the treatment of overt HE, with a significant decrease in mortality and shorter hospital stay 6.
• Rifaximin has been shown to be effective in reducing the risk of HE-related hospitalization, and may result in substantial reductions in healthcare resource utilization over the long term 4, 5.

Patient-Reported Outcomes

• Patients with HE treated with lactulose or rifaximin reported improvements in important patient-reported outcomes (PROs), including overall health-related quality of life, social functioning, and sleep 7.
• Lactulose significantly improved overall patient-reported health-related quality of life in patients with covert HE, while rifaximin demonstrated a non-statistically significant mean difference in the total Sickness Impact Profile 7.