What is the effect of Polyethylene Glycol (PEG) compared to lactulose in Hepatic Encephalopathy?

Polyethylene Glycol vs. Lactulose in Hepatic Encephalopathy

Polyethylene glycol (PEG) is superior to lactulose for the treatment of overt hepatic encephalopathy, demonstrating faster resolution of symptoms and shorter hospital stays without increasing adverse effects. 1, 2

Comparative Efficacy

PEG vs. Lactulose

• PEG shows significantly better outcomes compared to lactulose:
  • Higher clinical efficacy (RR=1.46; 95% CI: 1.26-1.68) 1
  • Shorter hospital stays (WMD=-1.78 days; 95% CI: -2.72 to -0.85) 1
  • Faster resolution of hepatic encephalopathy (HE) 3, 2
  • Greater improvement in HE Scoring Algorithm (HESA) scores at 24 hours 2

Current Standard Treatment

• Lactulose has traditionally been the first-line treatment for HE according to both American and European guidelines 4
• Lactulose works by:
  • Acidifying the colon
  • Reducing ammonia production and absorption
  • Altering gut flora
  • Accelerating intestinal transit time 5

Treatment Algorithm for Hepatic Encephalopathy

1. First step: Identify and treat precipitating factors (infections, GI bleeding, electrolyte disturbances) 4, 5

2. For acute overt HE:

   • PEG should be considered first-line therapy due to faster resolution of symptoms (24-hour improvement rate of 94% vs. 72% for lactulose) 3
   • Initial dosing: Standard PEG electrolyte solution as used in bowel preparation
   • Monitor for clinical improvement within 24 hours

3. If PEG is unavailable or contraindicated:

   • Use lactulose at 25 mL every 1-2 hours until 2 soft bowel movements per day 4
   • Maintenance: Titrate to maintain 2-3 soft bowel movements daily 5
   • For non-responsive patients: Add rifaximin 550 mg twice daily 4

4. For prevention of recurrent HE:

   • Lactulose is recommended for prevention of recurrent episodes 4
   • Add rifaximin for prevention after second episode 4

Important Considerations

Advantages of PEG

• No significant difference in adverse events compared to lactulose (RR=0.75; 95% CI: 0.48-1.19) 1
• Similar effects on serum ammonia levels at 24 hours 1
• More rapid improvement in mental status 2

Cautions with Lactulose

• Overuse can lead to serious complications:
  • Aspiration
  • Dehydration
  • Hypernatremia
  • Perianal skin irritation
  • Paradoxical worsening of HE 4

Monitoring

• Assess mental status improvement within 24-48 hours
• Monitor bowel movements (target: 2-3 soft stools daily)
• Evaluate for signs of dehydration or electrolyte disturbances

Special Situations

• Upper GI bleeding: Lactulose is recommended for primary prophylaxis 4
• Post-TIPS HE: Routine prophylactic therapy with lactulose is not recommended 4
• Patients unable to take oral medications: Consider lactulose retention enema (300 mL lactulose mixed with 700 mL water) 5

The evidence clearly demonstrates that PEG offers significant advantages over lactulose in the treatment of overt hepatic encephalopathy, with faster symptom resolution and shorter hospital stays without increasing adverse effects.