What is the recommended dose of lactulose (a non-absorbable sugar) for treating constipation and hepatic encephalopathy?

Lactulose Dosing

For constipation, start with 15-30 mL (10-20 g) daily and titrate up to a maximum of 60 mL (40 g) daily based on response; for hepatic encephalopathy, give 30-45 mL (20-30 g) every 1-2 hours initially until achieving 2 bowel movements daily, then maintain with 30-45 mL three to four times daily. 1, 2

Constipation Dosing

Initial dose: Begin with 15-30 mL (10-20 g) once daily for chronic idiopathic constipation. 1, 2

Titration strategy:

• If inadequate response after several days, increase to a maximum of 60 mL (40 g) daily 1, 3
• Reduce dose by half if patient has 3 consecutive days with defecation 3
• Double the dose if no defecation occurs for more than 48 hours 3
• Target goal is 2-3 soft stools daily 1, 2

Important caveats: Lactulose should only be used after failure or intolerance to over-the-counter therapies like polyethylene glycol or magnesium oxide, as it has very low certainty of evidence for constipation. 1 Bloating and flatulence are dose-dependent side effects that commonly limit tolerability, particularly at higher doses. 1, 3

Hepatic Encephalopathy Dosing

Acute/Overt Hepatic Encephalopathy

Initial aggressive phase: Give 30-45 mL (20-30 g) every 1-2 hours orally or via nasogastric tube until the patient achieves at least 2 soft bowel movements daily. 1, 3, 2 This hourly dosing induces rapid laxation needed in the initial phase. 2

Maintenance phase: Once laxative effect is achieved, reduce to 30-45 mL (20-30 g) administered 3-4 times daily to maintain 2-3 soft stools per day. 1, 4, 2

Alternative route for severe cases: If the patient is in impending coma, coma stage, or cannot take oral medications due to aspiration risk or physical interference from procedures, administer 300 mL lactulose mixed with 700 mL water as a retention enema via rectal balloon catheter. 1, 2 Retain the solution for at least 30 minutes to 60 minutes. 1, 2 This can be repeated every 4-6 hours. 2

Timeline expectations: Improvement may occur within 24 hours but may not begin before 48 hours or even later. 2 Reversal of coma may take place within 2 hours of the first enema in some patients. 2

Chronic/Maintenance Hepatic Encephalopathy

Standard dosing: Continue 20-30 g (30-45 mL) administered 3-4 times daily, titrated to achieve 2-3 soft bowel movements per day. 1, 4, 5 Continuous long-term therapy is indicated to lessen severity and prevent recurrence. 2

Adjunctive therapy: Consider adding rifaximin 550 mg twice daily or 400 mg three times daily for improved outcomes, showing better recovery rates and shorter hospital stays compared to lactulose alone. 3, 4

Critical Safety Warnings

Avoid excessive dosing: Overuse can lead to serious complications including aspiration, dehydration, hypernatremia, severe perianal skin irritation, and paradoxically may precipitate hepatic encephalopathy through electrolyte disturbances. 3, 4, 6 It is a dangerous misconception that lack of effect from smaller doses is remedied by much larger doses. 6

Proper escalation strategy: If no response after appropriate dosing, investigate precipitating factors (infection, GI bleeding, constipation, medications) rather than escalating lactulose indefinitely. 6 The goal is adequate ammonia clearance, not achieving an arbitrary number of bowel movements beyond the evidence-based target of 2-3 daily. 6

Monitoring requirements: Monitor for perianal skin breakdown with chronic use, and watch for signs of dehydration and electrolyte disturbances. 6 If excessive bowel movements occur (>3 per day), reduce the dose immediately to prevent complications. 6, 7

Pediatric Dosing

Infants: The recommended initial daily oral dose is 2.5-10 mL in divided doses. 2

Older children and adolescents: Total daily dose is 40-90 mL. 2

Adjustment: If the initial dose causes diarrhea, reduce immediately; if diarrhea persists, discontinue lactulose. 2 As with adults, the goal is to produce 2-3 soft stools daily. 2

Alternative Agent

Lactitol: Can be used as an equivalent alternative at a dose of 67-100 g daily if lactulose is not tolerated, with similar efficacy and side effect profile. 1, 3, 7