When is lactulose (lactose) used vs rifaximin in the treatment of hepatic encephalopathy?

Lactulose vs Rifaximin in Hepatic Encephalopathy Management

Lactulose should be used as first-line therapy for initial episodes of overt hepatic encephalopathy (OHE), while rifaximin should be added to lactulose after a second episode of OHE recurrence. 1

First-Line Treatment: Lactulose

• Lactulose is the recommended first-line therapy for initial episodes of overt hepatic encephalopathy due to its effectiveness and lower cost 2, 1
• Initial dosing: 25-45 mL (20-30g) every 1-2 hours until at least two soft bowel movements per day are produced 2, 1
• Maintenance dosing: Titrate to achieve 2-3 soft bowel movements daily 2, 1
• Lactulose works by converting ammonia to ammonium (making it less absorbable) and creating an osmotic laxative effect that flushes ammonia from the intestines 2
• For patients unable to take medications orally, lactulose can be administered via nasogastric tube 2
• For severe HE (West-Haven criteria grade 3 or more), lactulose enema (300 mL lactulose and 700 mL water) can be performed 3-4 times daily 2

When to Add Rifaximin

• Add rifaximin to lactulose therapy after a second recurrence of OHE 1, 3
• Rifaximin dosing: 550 mg twice daily or 400 mg three times daily 2, 4
• Rifaximin is a non-absorbable antibiotic that inhibits bacterial RNA synthesis, reducing ammonia production 2
• Combination therapy of rifaximin plus lactulose has been shown to:
  • Improve recovery from HE within 10 days (76% vs. 44% with lactulose alone) 2
  • Reduce hospital stays (5.8 vs. 8.2 days with lactulose alone) 2
  • Decrease mortality rates compared to lactulose alone (RR 0.57; 95% CI, 0.41-0.80) 5
  • Reduce hospitalization rates in patients resistant to lactulose therapy 6

Important Considerations

• Rifaximin is FDA-approved specifically for "reduction in risk of overt hepatic encephalopathy recurrence in adults" 4
• In clinical trials for rifaximin, 91% of patients were using lactulose concomitantly 4
• Using rifaximin alone without lactulose is not supported by solid evidence 1
• Avoid overuse of lactulose as it can lead to complications including aspiration, dehydration, hypernatremia, severe perianal skin irritation, and can even precipitate HE 1
• Rifaximin may have limited use in severe HE (West-Haven criteria grade 3 or more) due to the need for oral administration 2

Alternative Therapies for Non-Responders

• For patients not responsive to conventional therapy, consider:
  • Oral branched-chain amino acids (BCAAs) 1
  • IV L-ornithine L-aspartate (LOLA) 1
• Neomycin and metronidazole are not recommended for routine management of HE due to significant side effects:
  • Neomycin: intestinal malabsorption, nephrotoxicity, ototoxicity 2, 1
  • Metronidazole: peripheral neuropathy 2, 1

Common Pitfalls to Avoid

• Failing to identify and treat precipitating factors for HE 1
• Using rifaximin as first-line therapy instead of lactulose 1
• Not adding rifaximin after multiple recurrences despite lactulose treatment 1
• Excessive lactulose dosing leading to complications 1
• Not considering rifaximin add-on therapy in lactulose-resistant cases 6