From the Guidelines
Encephalopathy should be treated by addressing the underlying cause and providing supportive care, with lactulose and rifaximin being standard treatments for hepatic encephalopathy, as supported by the most recent guidelines 1.
Causes and Presentation
Encephalopathy is a general term describing altered brain function or structure due to various causes, including infections, metabolic disorders, toxins, oxygen deprivation, and systemic diseases. It presents with confusion, altered consciousness, personality changes, and impaired thinking.
Treatment
- For hepatic encephalopathy, lactulose (15-30 mL orally 2-4 times daily) and rifaximin (550 mg twice daily) are standard treatments 1.
- For uremic encephalopathy, dialysis may be necessary.
- Wernicke's encephalopathy requires immediate thiamine (500 mg IV three times daily for 2-3 days, then 250 mg daily).
Management
Management includes:
- Maintaining airway protection
- Correcting electrolyte imbalances
- Treating infections with appropriate antibiotics
- Discontinuing toxic substances
Recovery
Recovery depends on the cause, severity, and how quickly treatment begins, with some patients requiring rehabilitation for persistent cognitive deficits.
Diagnosis
The diagnosis of hepatic encephalopathy is through exclusion of other causes of brain dysfunction (GRADE II-2, A, 1) 1.
Stages of Severity
Hepatic encephalopathy should be divided into various stages of severity, reflecting the degree of self-sufficiency and the need for care (GRADE III, B, 1) 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.
Lactulose is used for the prevention and treatment of portal-systemic encephalopathy.
- The clinical response has been observed in about 75% of patients.
- Improvement in the patient’s condition may occur within 24 hours but may not begin before 48 hours or even later.
- Continuous long-term therapy is indicated to lessen the severity and prevent the recurrence of portal-systemic encephalopathy 2.
- The goal of treatment is reversal of the coma stage in order that the patient may be able to take oral medication 2.
From the Research
Definition and Treatment of Encephalopathy
- Encephalopathy is a serious complication of acute and chronic liver disease associated with severe morbidity and mortality 3.
- Hepatic encephalopathy (HE) is a common encephalopathy and one of the very few that are treatable, with lactulose remaining a standard pharmaceutical intervention 4.
Pharmacologic Management
- Non-absorbable disaccharides (lactulose and lactitol), rifaximin, and branched chain amino acids (BCAA) have been shown to have beneficial effects on HE manifestations and prevention of HE episodes 3.
- The addition of rifaximin to non-absorbable disaccharides versus rifaximin alone was more beneficial than non-absorbable disaccharides used alone on both outcome measures 3.
- Lactulose is effective for the prevention of overt HE recurrence over the long term, and the addition of rifaximin to lactulose significantly reduces the risk of overt HE recurrence and HE-related hospitalization, compared with lactulose therapy alone 5.
- Other pharmacologic therapies for HE include antibiotics, electrolyte management, polyethylene glycol, albumin, branched-chain amino acids, probiotics, fecal microbiota transplant, zinc, and l-ornithine-l-aspartate 6.
Combination Therapy
- The combination of rifaximin and lactulose may be considered in the treatment of HE and in patients refractory to monotherapy 7.
- The combination of rifaximin and lactulose should be considered for the prevention of HE, especially after the second episode of HE recurrence 7.
- Currently, there are limited studies evaluating the use of combination therapy for the treatment of HE, and more research is needed to determine its efficacy and safety 7.