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

Lactulose Dosage and Use for Constipation and Hepatic Encephalopathy

Recommended Dosage for Hepatic Encephalopathy

For hepatic encephalopathy, the standard adult oral dosage of lactulose is 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

• Maintenance dosage should be adjusted to achieve 2-3 soft bowel movements daily 1
• Improvement may occur within 24 hours but may not begin before 48 hours or even later 2
• Continuous long-term therapy is indicated to prevent recurrence of portal-systemic encephalopathy 2
• Lactulose is the first-line treatment for hepatic encephalopathy as recommended by both American and European liver disease associations 1

For Acute/Severe Hepatic Encephalopathy

• Hourly doses of 30-45 mL may be used to induce rapid laxation in the initial phase of therapy 2
• For patients in impending coma or coma stage where aspiration risk exists, rectal administration is recommended 2:
  • 300 mL of lactulose mixed with 700 mL of water or physiologic saline
  • Retained for 30-60 minutes
  • May be repeated every 4-6 hours
  • Oral administration should begin before discontinuing rectal administration 2

Recommended Dosage for Constipation

• For constipation in adults, the usual oral dosage is 30-45 mL (20-30g) three or four times daily 2
• Dosage may be adjusted every day or two to produce 2-3 soft stools daily 2

Pediatric Dosing

• Limited information exists on pediatric dosing 2
• Recommended initial daily oral doses 2:
  • Infants: 2.5-10 mL in divided doses
  • Older children and adolescents: 40-90 mL total daily dose
• If diarrhea occurs, reduce dose immediately or discontinue if persistent 2

Mechanism of Action

• Lactulose is a synthetic disaccharide that is not absorbed in the small intestine 3
• In the colon, it is fermented by bacteria to produce short-chain fatty acids and gases 3, 4
• This fermentation:
  • Lowers colonic pH, which favors formation of non-absorbable NH4+ from NH3 4
  • Traps NH4+ in the colon, reducing plasma ammonia concentrations 4
  • Increases bacterial incorporation of nitrogen 5
  • Reduces breakdown of nitrogen-containing compounds to ammonia 5

Clinical Considerations and Pitfalls

• Identify and treat precipitating factors as the most important step in managing hepatic encephalopathy 1
• Lactulose is recommended for prevention of recurrent episodes after the initial episode, with rifaximin added after the second episode 1
• Overuse of lactulose can lead to complications such as 1:
  • Aspiration
  • Dehydration
  • Hypernatremia
  • Severe perianal skin irritation
  • Paradoxical precipitation of hepatic encephalopathy
• Cleansing enemas containing soap suds or other alkaline agents should not be used with lactulose enemas 2
• Lactulose is removed by hemodialysis with a removal rate of approximately 83.6% 6

Special Populations

• For hemodialysis patients, no plasma accumulation is expected when coordinating with dialysis 6
• Lactulose may have additional benefits for patients with chronic renal insufficiency by reducing nitrogen-related products in serum 6