Why do cirrhosis patients need lactulose?

Lactulose in Cirrhosis: Managing Hepatic Encephalopathy

Lactulose is the first-line treatment for hepatic encephalopathy in cirrhosis patients because it reduces blood ammonia levels by 25-50%, which directly improves mental status and prevents recurrence of encephalopathy episodes. 1

Mechanism of Action

Lactulose works through multiple mechanisms to reduce ammonia levels in patients with cirrhosis:

• Acts as a non-absorbable disaccharide that acidifies the colon, converting ammonia (NH₃) to ammonium (NH₄⁺), which cannot be absorbed
• Promotes growth of beneficial bacteria that do not produce ammonia
• Creates an osmotic laxative effect that accelerates intestinal transit time, reducing ammonia absorption
• Decreases production of ammonia-forming bacteria in the gut

Treatment Protocol for Hepatic Encephalopathy

Initial Treatment

• Start with 25-45 mL (20-30g) of lactulose every 1-2 hours until the patient has at least 2 soft bowel movements per day 2, 3
• For patients unable to take oral medications, administer via nasogastric tube or as a retention enema (300 mL lactulose mixed with 700 mL water) 2

Maintenance Therapy

• Titrate dose to maintain 2-3 soft bowel movements daily 2
• Typical maintenance dose is 20-30g (25-45 mL) 3-4 times daily 2

Add-on Therapy

• For patients who experience a second episode of overt HE while on lactulose, add rifaximin (550 mg twice daily) 2
• For non-responders, consider adding oral branched-chain amino acids (0.25 g/kg/day) or IV L-ornithine L-aspartate (30 g/day) 2

Predictors of Non-Response to Lactulose

Approximately 22% of patients may not respond to lactulose therapy. Factors associated with non-response include 4:

• High MELD score
• Elevated white blood cell count
• Low mean arterial pressure
• Presence of hepatocellular carcinoma
• Low serum sodium

Efficacy and Evidence

• Lactulose reduces the risk of recurrent hepatic encephalopathy by 56% compared to placebo 5
• Number needed to treat to prevent one episode of overt HE is 6 6
• Lactulose improves psychometric test performance even in patients with subclinical (minimal) hepatic encephalopathy 7

Common Pitfalls and Caveats

1. Overuse of lactulose can lead to complications including:

   • Dehydration and electrolyte disturbances
   • Hypernatremia
   • Severe perianal skin irritation
   • Paradoxical worsening of encephalopathy 2, 3

2. Poor adherence is common due to:

   • Large volumes required
   • Frequent dosing
   • Unpleasant taste
   • Side effects (abdominal discomfort, flatulence) 8

3. Failure to identify precipitating factors of HE, which should be addressed concurrently:

   • Infections (especially spontaneous bacterial peritonitis)
   • GI bleeding
   • Electrolyte disturbances
   • Constipation
   • Medications (sedatives, diuretics)

Special Considerations

• Prophylactic lactulose is recommended for patients with cirrhosis and upper GI bleeding 6
• Routine prophylactic therapy is not recommended for prevention of post-TIPS hepatic encephalopathy 2
• Lactulose may be discontinued if precipitating factors are well-controlled or liver function improves 3

By following these guidelines, clinicians can effectively manage hepatic encephalopathy in cirrhosis patients, reducing morbidity and improving quality of life while minimizing complications from treatment.