Lactulose for Hepatic Encephalopathy

Lactulose is a non-absorbable disaccharide that is first-line treatment for overt hepatic encephalopathy and for preventing its recurrence. It acidifies the colon and traps ammonia as ammonium, while the laxative effect clears nitrogenous waste.

Classification. Osmotic laxative; ammonia-lowering agent.

Mechanism. Colonic bacteria ferment lactulose to lactic and acetic acids, lowering colonic pH. This converts ammonia (NH3) to non-absorbable ammonium (NH4+), traps it in the lumen, and reduces ammonia-producing bacteria. The osmotic effect increases stool water and transit.

Pharmacodynamics. Onset 24 to 48 hours; effect depends on reaching 2 to 3 soft stools daily.

Pharmacokinetics. Less than 3% absorbed. The absorbed fraction is excreted unchanged in urine.

Metabolism. Fermented by colonic bacteria to short-chain fatty acids, lactic acid and gases.

Adult doses unless stated. Syrup contains 10 g in 15 mL (667 mg/mL).

Acute overt hepatic encephalopathy.

• Oral: 30 to 45 mL every 1 to 2 hours until a soft stool is passed, then 15 to 45 mL two to three times daily, titrated to 2 to 3 soft stools daily.

• Enema (if the patient cannot take oral): 300 mL lactulose in 700 mL of water or saline, retained for 30 to 60 minutes, repeated every 4 to 6 hours.

• Nasogastric tube: same oral dose, flushed with water.

Prevention of recurrence (secondary prophylaxis).

• 15 to 45 mL two to three times daily, titrated to 2 to 3 soft stools daily.

• Continue long term, and add rifaximin 550 mg twice daily after a second episode.

Primary prophylaxis after gastrointestinal bleeding in cirrhosis. 30 to 45 mL every 6 hours for 48 hours, then adjust to 2 to 3 soft stools daily.

Constipation (reference). 15 to 30 mL daily, adjusted to response.

Children. Hepatic encephalopathy: 40 to 90 mL daily in divided doses, adjusted for 2 to 3 soft stools daily; specialist directed.

Kidney and liver adjustment. No fixed adjustment; titrate to stool output. Avoid diarrhoea with dehydration, which worsens kidney function and encephalopathy.

Contraindications. Galactosaemia; gastrointestinal obstruction; hypersensitivity.

Common adverse effects. Flatulence, bloating, abdominal cramp, nausea and diarrhoea, usually settling in a few days.

Serious adverse effects.

• Over-treatment: severe diarrhoea with dehydration, hypernatraemia, hypokalaemia and kidney injury, which can precipitate or worsen encephalopathy.

• Perianal skin irritation.

• Toxic megacolon and aspiration risk in a drowsy patient.

• Rare bowel perforation after surgery or with colonic obstruction.

Major interactions.

• Other laxatives: additive effect; avoid unless advised.

• Potassium-wasting drugs (loop diuretics, thiazides): increase hypokalaemia with diarrhoea.

• Antacids and neomycin: may reduce lactulose effect.

• Diathermy in the bowel: avoid while gas is present, as lactulose fermentation produces hydrogen.

Special groups.

• Pregnancy: acceptable.

• Breastfeeding: compatible.

• Children: dose by weight under specialist care.

• Older adults: monitor sodium, potassium and fluid status.

• Diabetes: the syrup contains small amounts of free sugars (lactose, galactose); little effect on glucose in normal doses.

• Kidney impairment: avoid dehydration.

• Liver impairment: first-line.

• Regional: widely available and low cost; lactulose and the treatment of precipitants (infection, bleeding, constipation, sedatives) are the foundation of care in East Africa.

Formulations. Oral solution 10 g in 15 mL (667 mg/mL); powder sachets.

Administration.

• Take undiluted or mixed with water or juice; swallow quickly to limit sweet taste.

• Titrate every 1 to 2 days to 2 to 3 soft stools daily.

• Reduce the dose if there are more than 4 loose stools daily.

• Advise carers to record stool frequency daily.

Baseline. Mental state grade, hydration, sodium, potassium, creatinine, and precipitants (infection, bleeding, constipation, drugs, electrolyte disturbance).

Monitoring.

• Stool frequency and consistency.

• Mental state, sleep, asterixis and orientation.

• Sodium, potassium and creatinine.

• Fluid balance and weight.

Therapeutic drug monitoring. Not applicable.

Stopping. Long-term treatment is usual after an episode. Stop temporarily for severe diarrhoea and review dose.

Referral and escalation. Admit for grade 2 or higher encephalopathy, no response in 48 hours, sepsis, bleeding or marked electrolyte disturbance. Consider rifaximin addition and liver transplant assessment.