From the Guidelines
For severe agitation and hepatic encephalopathy, the first-line treatment is lactulose, administered at 25-30 mL orally every 1-2 hours until bowel movements occur, then adjusted to 15-30 mL 2-4 times daily to achieve 2-3 soft bowel movements per day, as recommended by the most recent guidelines 1.
Treatment Options
- Lactulose is the primary treatment for hepatic encephalopathy, and it works by reducing ammonia production and absorption in the gut 1.
- For patients unable to take oral medications, lactulose enemas (300 mL in 700 mL water) can be given rectally every 4-6 hours, as suggested by previous guidelines 1.
- Rifaximin 550 mg twice daily can be added as an adjunct therapy for patients who don't respond adequately to lactulose alone, based on the recommendations of the Kasl clinical practice guidelines 1.
Management of Agitation
- For severe agitation, low-dose benzodiazepines should be avoided if possible due to the risk of worsening encephalopathy, as they can exacerbate the condition 1.
- Instead, consider haloperidol 0.5-2 mg IV/IM every 4-8 hours as needed, with careful monitoring for extrapyramidal side effects, as recommended by the clinical policy for critical issues in the diagnosis and management of the adult psychiatric patient in the emergency department 1.
- Dexmedetomidine infusion (0.2-0.7 mcg/kg/hr) may be used in ICU settings for severe, refractory agitation, providing a safe and effective alternative to traditional sedatives.
Addressing Precipitating Factors
- Addressing precipitating factors is crucial, including treating infections, correcting electrolyte abnormalities, stopping sedating medications, and managing gastrointestinal bleeding if present, as emphasized by the French recommendations for the diagnosis and management of hepatic encephalopathy 1.
- Ensuring adequate nutrition with 1.2-1.5 g/kg/day of protein supports hepatic recovery, and protein restriction is no longer routinely recommended, according to the most 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. The efficacy of intramuscular olanzapine for injection for the treatment of agitation was established in 3 short-term (24 hours of IM treatment) placebo-controlled trials in agitated adult inpatients from 2 diagnostic groups: schizophrenia and bipolar I disorder (manic or mixed episodes)
The treatment options for severe agitation and hepatic (liver) encephalopathy are:
- Lactulose for the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma 2
- Olanzapine for the treatment of agitation in patients with schizophrenia or bipolar I disorder (manic or mixed episodes) 3 Note that these options may not be directly related to treating both conditions simultaneously, and the use of these medications should be carefully considered by a healthcare professional.
From the Research
Treatment Options for Severe Agitation and Hepatic Encephalopathy
- The primary treatment for hepatic encephalopathy is lactulose, which is effective in minimal, overt, and recurrent hepatic encephalopathy 4, 5.
- Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated 4, 5, 6.
- Branch chain amino acids are beneficial in subjects who are protein intolerant 4, 7.
- L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy 4, 7.
- Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy 4, 6.
- Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients 4, 6.
- For severe agitation in hepatic encephalopathy, management includes physical restraint and medication, with haloperidol being a safer choice in the presence of liver disease 8.
- Benzodiazepines are best avoided in the management of agitation due to the risk of precipitating coma 8.
- Phenytoin and gabapentin are relatively preferred drugs for seizure management in hepatic encephalopathy, with monitoring of drug levels being desirable 8.