From the Guidelines
To reduce hyperammonemia, the most effective approach is to use nonabsorbable disaccharides, such as lactulose, as the first line of treatment, as recommended by the most recent guidelines 1. The goal of treatment is to reduce ammonia production in the gut and improve the body's ability to clear ammonia.
- Lactulose works by trapping ammonia in the gut and promoting its excretion, and it is recommended to be administered orally at a dose of 15-30 mL 2-4 times daily.
- Rifaximin, an oral nonsystemic antibiotic, can also be used to decrease ammonia-producing bacteria, at a dose of 550 mg twice daily.
- Dietary modifications, such as reducing protein intake to 0.6-0.8 g/kg/day and focusing on plant proteins, can also help reduce ammonia production.
- Staying well-hydrated and avoiding dehydration is crucial, as dehydration can worsen ammonia levels.
- For severe elevations, especially with hepatic encephalopathy symptoms, seeking immediate medical attention is necessary, as intravenous medications and supportive care may be required.
- Regular monitoring of ammonia levels is essential to track progress, and addressing any precipitating factors, such as gastrointestinal bleeding, infection, or medication side effects, is crucial for effective management.
- Other treatments, such as L-ornithine L-aspartate (LOLA) and probiotics, may also be considered, but the evidence for their use is limited, and they should be used with caution 1.
- It is also important to note that the use of lactulose and rifaximin should be titrated to achieve two to three soft stools per day, and the dose should be adjusted accordingly to avoid overuse and potential complications 1.
From the FDA Drug Label
Controlled studies have shown that lactulose solution therapy reduces the blood ammonia levels by 25 to 50%; this is generally paralleled by the improvement in the patients’ mental state and by an improvement in EEG patterns. Neomycin sulfate has been shown to be effective adjunctive therapy in hepatic coma by reduction of the ammonia-forming bacteria in the intestinal tract. The subsequent reduction in blood ammonia has resulted in neurologic improvement.
To reduce hyperammonemia, the following options can be considered:
- Lactulose (PO) therapy, which has been shown to reduce blood ammonia levels by 25 to 50% 2
- Neomycin (PO) therapy, which reduces ammonia-forming bacteria in the intestinal tract, resulting in a subsequent reduction in blood ammonia 3
From the Research
Reducing Hyperammonemia
To reduce hyperammonemia, several strategies can be employed, including:
- Targeting ammonia levels itself 4
- Targeting inflammation, which makes the brain susceptible to the deleterious effect of ammonia 4
- Reducing ammonia production, absorption, or elimination 4 Some specific treatments that have been shown to be effective in reducing hyperammonemia include:
- Lactulose 4, 5, 6, 7, 8
- Rifaximin 4, 5, 6, 8
- Probiotics, such as Bacillus subtilis HU58 7
- Closure of large portosystemic shunts 4
- Molecular adsorbent recirculating system (MARS) 5
Mechanisms of Action
The mechanisms of action of these treatments vary, but may include:
- Enhancing ammonia uptake by small bowel bacteria (lactulose) 6
- Reducing gut ammonia production (rifaximin) 6
- Promoting the growth of urease-producing gut bacteria and reducing colon pH (lactulose) 7
- Reducing blood ammonia absorption (lactulose) 7
Combination Therapy
Combination therapy, such as lactulose plus rifaximin, may be more effective than monotherapy in reducing hyperammonemia and improving outcomes in patients with hepatic encephalopathy 8