What is the indication for lactulose (syrup)?

Lactulose Syrup Indications

Lactulose syrup is indicated for the treatment and prevention of hepatic encephalopathy (portal-systemic encephalopathy), including hepatic pre-coma and coma, and for the treatment of constipation. 1

Primary Indication: Hepatic Encephalopathy

Lactulose is the first-line treatment for overt hepatic encephalopathy (OHE) in patients with chronic liver disease. 2

Treatment of Acute Episodes

• Lactulose is generally used as initial treatment for overt hepatic encephalopathy episodes 2
• The FDA-approved indication specifically covers prevention and treatment of portal-systemic encephalopathy, including hepatic pre-coma and coma stages 1
• Clinical response is observed in approximately 75% of patients, with blood ammonia levels reduced by 25-50% 1

Dosing for Acute Treatment

• Initial dose: 25 mL of lactulose syrup every 1-2 hours until at least two soft or loose bowel movements per day are produced 2, 3
• Maintenance: Titrate to maintain 2-3 soft bowel movements per day 2, 3
• The European guidelines suggest 25 mL every 12 hours as an alternative initial regimen 2

Prevention of Recurrent Episodes

• After the first episode of overt hepatic encephalopathy, lactulose is recommended for secondary prophylaxis to prevent recurrence 2, 3
• Lactulose reduces the risk of recurrent overt HE episodes (risk ratio 0.58,95% CI 0.50-0.69) 2
• After a second episode, rifaximin should be added to lactulose therapy 2, 3

Covert Hepatic Encephalopathy

• Lactulose may be used to improve quality of life and reduce the risk of progression to overt HE in patients with covert (minimal) hepatic encephalopathy 3

Secondary Indication: Constipation

• Lactulose is therapeutically used for constipation due to its osmotic laxative effect 4, 5
• The drug is not absorbed from the small intestine and is fermented by colonic bacteria, producing short-chain fatty acids that lower colonic pH and increase osmotic pressure 4, 5

Special Clinical Situations

Gastrointestinal Bleeding in Cirrhosis

• Rapid removal of blood from the GI tract using lactulose (by nasogastric tube or enemas) can prevent hepatic encephalopathy in patients with cirrhosis presenting with GI bleeding 2
• Lactulose significantly reduces HE incidence in this setting (7% vs. 28%, p <0.01) 2

TIPS Procedure

• Rifaximin can be considered for prophylaxis prior to non-urgent TIPS placement, with lactulose as a potential adjunct requiring further study 2

Critical Safety Considerations

Overuse of lactulose is dangerous and can lead to serious complications including aspiration, dehydration, hypernatremia, severe perianal skin irritation, and can paradoxically precipitate hepatic encephalopathy. 2, 3

Common Pitfalls to Avoid

• Do not use excessively large doses - it is a misconception that lack of effect with smaller amounts is remedied by much larger doses 2
• Always reduce dose after achieving initial bowel movement response - failure to titrate down increases complication risk 2
• If lactulose is ineffective, search for unrecognized precipitating factors and competing causes of encephalopathy rather than increasing the dose 2

Mechanism of Action

• Lactulose is a synthetic disaccharide not absorbed from the small intestine 4, 5
• It is fermented by colonic bacteria, producing short-chain fatty acids and lowering colonic pH 4, 5
• This acidification traps ammonia in the colon as ammonium ion (NH4+), preventing its absorption 4, 5, 6
• The osmotic effect produces a cathartic action that flushes ammonia from the intestines 3, 6
• Lactulose increases beneficial bacteria that do not produce ammonia 3