What is the recommended dosage and use of lactulose for constipation and hepatic encephalopathy?

Lactulose Dosage and Use for Constipation and Hepatic Encephalopathy

Lactulose is recommended as the first-line treatment for hepatic encephalopathy (HE) with a standard adult oral dosage of 25-45 mL (20-30g) every 1-2 hours initially until at least two soft bowel movements per day are produced, then titrated to maintain 2-3 soft stools daily. 1, 2

Dosage for Hepatic Encephalopathy

Oral Administration

• Initial dosage: 25-45 mL (20-30g) every 1-2 hours until at least two soft bowel movements per day are produced 1, 2
• Maintenance dosage: Adjust to achieve 2-3 soft bowel movements daily 1
• Long-term therapy is indicated to prevent recurrence of portal-systemic encephalopathy 2
• Improvement may occur within 24 hours but may not begin before 48 hours or even later 2

Rectal Administration (for patients in impending coma or unable to take oral medication)

• 300 mL lactulose mixed with 700 mL water or physiological saline as retention enema 2
• Retain for 30-60 minutes 2
• May repeat every 4-6 hours if evacuated too promptly 2
• Transition to oral administration as soon as patient is able to take medication by mouth 2

Dosage for Constipation

• Adult: 2-3 tablespoonfuls (30-45 mL, containing 20-30g of lactulose) three or four times daily 2
• Adjust every 1-2 days to produce 2-3 soft stools daily 2

Pediatric Dosage

• Infants: 2.5-10 mL daily in divided doses 2
• Older children and adolescents: 40-90 mL total daily dose 2
• If diarrhea occurs, reduce dose immediately; if diarrhea persists, discontinue lactulose 2

Mechanism of Action

• Lactulose is a synthetic disaccharide that is not absorbed in the small intestine 3
• It is fermented by colonic bacteria to short-chain fatty acids and gases, which lowers colonic pH 3, 4
• The acidic environment favors conversion of ammonia (NH3) to ammonium (NH4+), which cannot be absorbed, reducing plasma ammonia levels 4
• Lactulose also increases the count of beneficial bacteria that do not produce ammonia 1
• The osmotic effect produces a laxative action that helps flush ammonia from the intestines 1

Clinical Recommendations for Hepatic Encephalopathy

First Episode of Overt HE

• Identify and treat precipitating factors (most important step, as nearly 90% of patients can be treated with just correction of the precipitating factor) 1
• Lactulose is the first choice for treatment of episodic overt HE 1

Prevention of Recurrent Episodes

• Lactulose is recommended for prevention of recurrent episodes after the initial episode 1
• Rifaximin (400 mg three times/day or 550 mg twice/day) should be added to lactulose after the second episode 1

Special Considerations

• Routine prophylactic therapy with lactulose or rifaximin is not recommended for prevention of post-TIPS HE 1
• Under circumstances where precipitating factors have been well controlled or liver function/nutritional status improved, prophylactic therapy may be discontinued 1
• For covert HE, treatment with lactulose or rifaximin is suggested to improve quality of life and reduce the risk of overt HE 1

Common Pitfalls and Caveats

• Overuse of lactulose can lead to complications such as aspiration, dehydration, hypernatremia, severe perianal skin irritation, and can even precipitate HE 1
• It is a misconception that lack of effect from smaller amounts of lactulose should be remedied with much larger doses 1
• Lack of effect should prompt a clinical search for unrecognized precipitating factors and competing causes for brain impairment 1
• Cleansing enemas containing soap suds or other alkaline agents should not be used with lactulose enemas 2
• In patients with impaired renal function on hemodialysis, lactulose is removed by dialysis at a rate of approximately 83.6% 5