What medication is used to treat hepatic encephalopathy and elevated ammonia levels?

Treatment of Hepatic Encephalopathy with Elevated Ammonia

Lactulose is the first-line medication for treating hepatic encephalopathy and elevated ammonia levels, dosed at 25 mL orally every 1-2 hours initially until producing 2-3 soft bowel movements daily, then titrated to maintain this frequency. 1, 2

First-Line Therapy: Lactulose

Lactulose should be initiated immediately as the primary treatment for overt hepatic encephalopathy, with the following dosing strategy: 1

• Initial dosing: 25 mL of lactulose syrup every 1-2 hours until achieving at least 2 soft or loose bowel movements per day 1
• Maintenance dosing: Titrate to maintain 2-3 bowel movements daily 1
• Mechanism: Reduces blood ammonia levels by 25-50% through acidification of the gastrointestinal tract and inhibition of ammonia production by coliform bacteria 2
• Clinical response: Approximately 75% of patients show improvement in mental state and EEG patterns 2

Critical Dosing Pitfall

Avoid the common misconception that larger doses work better - excessive lactulose can cause serious complications including aspiration, dehydration, hypernatremia, severe perianal irritation, and paradoxically can even precipitate hepatic encephalopathy. 1

Add-On Therapy: Rifaximin

Rifaximin 550 mg twice daily should be added to lactulose for prevention of recurrent hepatic encephalopathy episodes. 1, 3

• Evidence: A multinational trial demonstrated superiority of rifaximin versus placebo when 91% of patients were concurrently using lactulose 1
• Important limitation: No solid data support using rifaximin alone without lactulose 1
• FDA indication: Approved for reduction in risk of overt hepatic encephalopathy recurrence in adults 3
• Mechanism: Decreases intestinal ammonia production and absorption by altering gastrointestinal flora 4

Alternative and Adjunctive Therapies

Intravenous L-Ornithine L-Aspartate (LOLA)

For persistent or severe hepatic encephalopathy, consider IV LOLA 30 g/day in combination with lactulose: 5, 6

• Leads to lower grade of hepatic encephalopathy within 1-4 days compared to lactulose alone 5
• Improves psychometric testing and lowers postprandial ammonia levels 1
• Note: Oral LOLA is ineffective 1

Oral Branched-Chain Amino Acids (BCAAs)

BCAAs can be used as an alternative or additional agent for patients not responding to conventional therapy: 1

• Meta-analysis of 8 RCTs showed improvement in manifestations of episodic hepatic encephalopathy 1
• Note: IV BCAAs have no effect on episodic hepatic encephalopathy 1

Probiotics

Probiotics are as effective as lactulose for secondary prophylaxis of hepatic encephalopathy: 7

• Open-label study showed fewer HE episodes with probiotics compared to no therapy, with no difference versus lactulose 1, 7
• Can be considered when lactulose is not tolerated 7

Treatment Algorithm

1. Identify and treat precipitating factors (infections, GI bleeding, constipation, medications, electrolyte abnormalities) 1

2. Start lactulose immediately: 25 mL every 1-2 hours until 2 bowel movements occur, then maintain 2-3 BMs daily 1

3. For recurrent episodes: Add rifaximin 550 mg twice daily to lactulose 1, 3

4. For persistent/refractory cases: Consider IV LOLA 30 g/day 5, 6

5. For non-responders to conventional therapy: Add oral BCAAs 1

Special Considerations

• Polyethylene glycol: May provide more rapid improvement when combined with lactulose, but requires further validation 1
• Neomycin: Avoid for long-term use due to ototoxicity, nephrotoxicity, and neurotoxicity 1
• Severe liver disease (MELD >25): Rifaximin has limited data in this population and shows increased systemic exposure 3