Makindo Medical Notes

💩 Lactulose is a non-absorbable disaccharide used both as an osmotic laxative and to prevent or treat hepatic encephalopathy. It acts by drawing water into the colon to soften stools and by reducing systemic ammonia levels through colonic acidification.

🧠 About

• Formed from galactose and fructose — not metabolised in the small intestine, hence remains within the gut lumen.
• Broken down by colonic bacteria into lactic acid, acetic acid, and small amounts of formic acid.
• These acids lower colonic pH, increasing osmotic pressure and stimulating peristalsis.
• Safe in most populations, including older adults and in hepatic disease.
• Onset of effect: typically within 24–48 hours.

⚙️ Mechanism of Action

• Osmotic effect: Lactulose is fermented by gut flora, generating organic acids that retain water in the bowel → increased faecal volume and softer stool.
• In hepatic encephalopathy (HE): Acidification of the colonic contents converts ammonia (NH₃) to ammonium (NH₄⁺), which is not absorbed. This reduces systemic ammonia and hence neurotoxicity.
• Also decreases the population of urease-producing bacteria, further lowering ammonia generation.
• May be beneficial in valproate-induced hyperammonaemia by the same mechanism.

🎯 Indications

• Constipation (including chronic and opioid-associated forms).
• Hepatic encephalopathy (prevention and treatment).
• Adjunct in valproate-related hyperammonaemia.

💊 Dose

• Constipation: 15 mL twice daily by mouth, titrated to produce soft stool.
• Hepatic encephalopathy: 30–50 mL three times daily by mouth, adjusting to achieve 2–3 soft stools/day. Rectal route can be used if oral route not tolerated (300 mL in 700 mL water retained for 30–60 min).
• Maintenance doses vary; may require lifelong use in advanced cirrhosis.

⚠️ Cautions

• Ensure adequate hydration to prevent dehydration or electrolyte imbalance.
• Monitor for excessive diarrhoea → may cause hypokalaemia and metabolic acidosis.
• Advise patients about possible flatulence and bloating during the first few days (from bacterial fermentation).

🚫 Contraindications

• Intestinal obstruction or perforation risk.
• Galactosaemia (contains galactose).
• Use with caution in patients on low-galactose diets or those intolerant of lactose.

💊 Adverse Effects

• Common: flatulence, abdominal bloating, cramping, nausea, diarrhoea.
• High doses: electrolyte disturbance, dehydration, faecal incontinence.
• Rare: hypersensitivity reactions (rash, urticaria).

🧩 Comparison of Laxative Types

🩺 Clinical Pearls

• In hepatic encephalopathy, the goal is loose stool, not profuse diarrhoea.
• If no improvement after 48 hours, add rifaximin for synergistic ammonia reduction.
• Encourage patients to continue long-term use even after mental status normalises — discontinuation often precipitates relapse.
• Useful teaching point: the difference between lactulose (osmotic) and macrogol (iso-osmotic polymer) in frail elderly patients.

📚 References

• BNF: Lactulose
• NICE CKS: Constipation in adults (2024)
• EASL Clinical Practice Guidelines. J Hepatol 2022 – Management of hepatic encephalopathy.
• Ong JP et al. Clin Gastroenterol Hepatol 2003;1(2):139–45 – Mechanisms of ammonia reduction by lactulose.