Hepatic Encephalopathy Management

Introduction to Hepatic Encephalopathy

Hepatic encephalopathy is a serious complication of liver disease that requires prompt diagnosis and treatment, as recommended by the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) 1, 2, 3, 4, 5

Lactulose should be used as first-line therapy for hepatic encephalopathy, with a recommended initial dose of 25-30 mL every 1-2 hours until at least two soft bowel movements per day are produced, then titrated to a maintenance dose of 30-45 mL three to four times daily to maintain 2-3 soft bowel movements per day, as recommended by the EASL and supported by Grade II-1, B, 1 evidence 1, 2, 3, 4, 5
Rifaximin (550 mg twice daily) should be added as an adjunct to lactulose after a second episode of overt hepatic encephalopathy within 6 months of the first episode, with a recommended dose of 550 mg twice daily (Grade I, A, 1) 2, 3, 6

Lactulose significantly reduces hepatic encephalopathy recurrence risk (20% vs 47% in those not receiving lactulose over 14 months) 6
Systematic reviews demonstrate lactulose effectively prevents overt hepatic encephalopathy episodes (RR 0.58, 95% CI 0.50-0.69) 6
Rifaximin plus lactulose significantly reduces hepatic encephalopathy recurrence compared to lactulose alone (22.1% vs 45.9%, NNT=4) 6

Rapid removal of blood from the GI tract using lactulose (via nasogastric tube or enemas) is recommended to prevent hepatic encephalopathy 6
Lactulose significantly reduces hepatic encephalopathy incidence in patients with GI bleeding (14% vs 40%, p<0.03) 6
The following treatments may be considered for acute management:

2, 3, 6

Consider liver transplantation evaluation for patients with recurrent or persistent hepatic encephalopathy, as recommended by the AASLD and the Clinical and Molecular Hepatology guidelines, with a strength of evidence of Grade I 4, 6, 7
Identify and treat precipitating factors, such as infections, GI bleeding, electrolyte disturbances, constipation, and dehydration, and initiate lactulose treatment without delay, as recommended by the AASLD and EASL 1, 2, 3, 4, 5
Monitor mental status, serum ammonia levels, liver function tests, and electrolytes daily, particularly sodium and potassium, as recommended by the AASLD 4
Avoid benzodiazepines, which can worsen encephalopathy, as recommended by the EASL and AASLD 1, 8, 9, 5
Discontinue olanzapine immediately in patients with liver cirrhosis and hepatic encephalopathy due to the risk of worsening encephalopathy and potential hepatotoxicity, as recommended by the AASLD 4

Implement non-pharmacological interventions for agitation/confusion, such as reorientation strategies, familiar caregivers, maintaining day-night cycle, and minimizing unnecessary stimulation, as recommended by the AASLD 4
Consider oral feeding for patients with mild hepatic encephalopathy, and enteral nutrition via nasogastric/naso-jejunal tube for those who cannot be fed orally, as recommended by the Clinical Nutrition guidelines 10
Consider ICU admission, intubation for airway protection, elevating the head of bed to 30 degrees, avoiding patient stimulation that may increase intracranial pressure, and immediate treatment of seizures if they occur, as recommended by the AASLD 7
Mechanical ventilation with protective settings should be used if intubation is required, according to the Anaesthesia guidelines 9

Probiotics may have fewer side effects than other treatments and have been found to have similar efficacy to lactulose in reducing episodes of hepatic encephalopathy 2, 3
Consider continuous kidney replacement therapy (CKRT) if ammonia levels remain high despite medical therapy, or if there is a rapid rise in ammonia levels, as suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines 11
High-dose continuous venovenous hemodialysis (CVVHD) is recommended as the first-line KRT for severe hyperammonemia by the American Society of Nephrology 11