When to add lactulose in decompensated liver cirrhosis?

From the Guidelines

Lactulose should be added in decompensated cirrhosis when a patient develops hepatic encephalopathy (HE) or as prevention in patients at high risk for HE, as recommended by the most recent guidelines 1. The typical starting dose is 25-30 mL orally two to three times daily, with the goal of achieving 2-3 soft bowel movements per day. For acute HE, higher doses may be used initially (30-45 mL every 1-2 hours) until clinical improvement, then reduced to maintenance dosing. For prevention after a first episode of HE, lactulose should be continued indefinitely at maintenance doses. Some key points to consider when using lactulose include:

• Lactulose works by acidifying the colon, which inhibits ammonia absorption and promotes its excretion, reducing blood ammonia levels, a key factor in the pathophysiology of HE 1.
• Lactulose also has a cathartic effect that helps eliminate nitrogen-containing compounds from the intestines.
• Patients should be monitored for dehydration, electrolyte imbalances, and excessive diarrhea, with dose adjustments made accordingly.
• If patients cannot tolerate oral lactulose, it can be administered as a retention enema (300 mL lactulose in 700 mL water) for acute management 1. It's also important to note that rifaximin can be added to lactulose for secondary prophylaxis following more than one episode of overt HE within 6 months of the first one, as it has been shown to decrease the risk of recurrence of overt HE and hospitalization 1.

From the FDA Drug Label

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. Continuous long-term therapy is indicated to lessen the severity and prevent the recurrence of portal-systemic encephalopathy.

Lactulose should be added in decompensated cirrhosis when there is a need to induce rapid laxation for the treatment of portal-systemic encephalopathy. The dosage may be adjusted to produce 2 or 3 soft stools daily.

• Initial phase: Hourly doses of 30 mL to 45 mL of lactulose solution may be used.
• Long-term therapy: The recommended daily dose is the same as the initial dose, which is 2 to 3 tablespoonfuls (30 mL to 45 mL) three or four times daily 2.

From the Research

Timing of Lactulose Administration in Decompensated Cirrhosis

• The decision to add lactulose in decompensated cirrhosis should be based on the presence of hepatic encephalopathy (HE) or the risk of developing it 3.
• Lactulose is commonly used to treat HE, and its efficacy has been established in various studies 4, 5, 6.
• The use of lactulose for primary prophylaxis of HE in patients with cirrhosis and acute upper gastrointestinal bleeding (AUGIB) has been debated, but a meta-analysis suggests that it reduces the incidence of HE after AUGIB 7.
• Factors that contribute to lactulose non-adherence include large volumes of lactulose, high frequency of dosing, difficulty remembering to take the medication, unpleasant taste, and medication side-effects 4.
• Predictors of nonresponse to lactulose include high baseline MELD, high total leukocyte count, low serum sodium, low mean arterial pressure, and presence of hepatocellular carcinoma 5.

Practical Considerations

• Lactulose should be titrated to achieve 2-3 soft stools per day, and patients should be monitored for signs of dehydration and electrolyte imbalances 6.
• The utility of monitoring stool consistency or pH remains unknown, and further research is needed to optimize the use of lactulose 6.
• Patient and caregiver education are critical to assure adherence to lactulose therapy, and pharmacists and nurses play an essential role in educating patients about proper medication use 4.