What can be given besides Lactulose to decrease ammonia levels in patients with hyperammonemia?

Alternatives to Lactulose for Reducing Ammonia Levels

Rifaximin is the primary alternative or add-on therapy to lactulose for reducing ammonia levels, with combination therapy showing superior outcomes compared to lactulose alone. 1, 2

First-Line Alternative: Rifaximin

Rifaximin should be added to lactulose (or used as monotherapy if lactulose is not tolerated) at a dose of 550 mg twice daily or 400 mg three times daily. 1, 2, 3

• Rifaximin is a non-absorbable antibiotic that inhibits bacterial RNA synthesis, reducing ammonia-producing bacteria in the gut 1
• Combination therapy with lactulose plus rifaximin achieves complete reversal of hepatic encephalopathy in 76% of patients versus 50.8% with lactulose alone (P<0.004) 4
• Adding rifaximin to lactulose-resistant patients significantly reduces hospitalization rates from 41.6% to 22.2% (P=0.02) and lowers ammonia levels from 124 μg/dL to 77 μg/dL at 24 weeks 5
• Mortality decreases from 49.1% to 23.8% when rifaximin is combined with lactulose (P<0.05) 4

Second-Line Options for Severe or Refractory Cases

Polyethylene Glycol (PEG)

• Administer 4 liters orally as a substitute for non-absorbable disaccharides 2
• PEG provides faster resolution of hepatic encephalopathy in some patients compared to lactulose alone 2, 3

Intravenous L-Ornithine-L-Aspartate (LOLA)

• Give 30 g/day intravenously for persistent or severe hyperammonemia not responding to lactulose intensification 2, 3
• LOLA leads to lower grades of hepatic encephalopathy within 1-4 days compared to lactulose alone 3
• This agent enhances ammonia metabolism through the urea cycle and glutamine synthesis 3

Branched-Chain Amino Acids (BCAAs)

• Dose at 0.25 g/kg/day as an ancillary treatment option 2
• Meta-analysis of 8 randomized controlled trials shows improvement in manifestations of episodic hepatic encephalopathy 3
• BCAAs can be used as an alternative or additional agent for patients not responding to conventional therapy 3

Special Circumstances

Valproate-Induced Hyperammonemia

• Administer intravenous L-carnitine 4.5 g/day for rapid reduction of ammonia levels 6
• L-carnitine supplementation can reduce ammonia from 594 μg/dL to 99 μg/dL within 12 hours with progressive restoration of mental status within 24 hours 6
• This is particularly relevant for psychiatric patients on valproic acid therapy who develop sudden hyperammonemia 6

Critical Care Settings

• Plasma exchange should be considered in critically ill patients with ammonia levels >150 μmol/L when available 2
• Molecular adsorbent recirculating system (MARS) has proven efficacy in severe hepatic encephalopathy, though mechanisms appear independent of ammonia reduction 7

Agents to Avoid

Neomycin should be avoided for long-term use due to ototoxicity, nephrotoxicity, and neurotoxicity 3

Treatment Algorithm

1. Start with rifaximin 550 mg twice daily (either as monotherapy if lactulose intolerant, or add to existing lactulose therapy) 1, 2, 3

2. If inadequate response after 1-2 weeks, add intravenous LOLA 30 g/day for 3-5 days 2, 3

3. Consider oral BCAAs 0.25 g/kg/day as adjunctive therapy for refractory cases 2, 3

4. For acute severe cases, use PEG 4 liters as an alternative cathartic agent 2

5. In critical illness with ammonia >150 μmol/L, pursue plasma exchange or MARS if available 2, 7

Common Pitfalls to Avoid

• Do not rely solely on ammonia levels to guide therapy; clinical improvement in mental status is the primary endpoint 8
• Do not use neomycin for chronic management due to significant toxicity risks 3
• Do not delay adding rifaximin in patients with recurrent episodes (≥2 episodes in 6 months), as combination therapy reduces recurrence from 46% to 22% 8, 3
• Ensure adequate hydration when using any cathartic agent to prevent dehydration-induced worsening of encephalopathy 1, 2