From the Guidelines
Treatment for hyperammonemia should prioritize the use of ammonia-scavenging agents, such as intravenous sodium benzoate and sodium phenylacetate, as recommended in the consensus guidelines for management of hyperammonaemia in pediatric patients receiving continuous kidney replacement therapy 1. The primary goal of treatment is to reduce ammonia production and enhance its elimination from the body.
- Stop protein intake to reduce ammonia production
- Administer i.v. glucose at an infusion rate of 8–10 mg/kg/min and i.v. lipids at 0.5 g/kg daily to provide adequate calories and reduce catabolism
- Use ammonia-scavenging agents, such as:
- i.v. sodium benzoate: maximum 12 g daily, given over 90 min as bolus then as maintenance over 24 h
- i.v. sodium phenylacetate: given over 90 min as bolus then as maintenance over 24 h
- i.v. l-arginine hydrochloride: given over 90 min as bolus then as maintenance over 24 h, with dosing based on weight and specific enzyme deficiencies
- Consider continuous kidney replacement therapy (CKRT) for patients with severe hyperammonemia, as recommended by the consensus panel for CKRT 1
- Monitor ammonia levels and neurological status closely to adjust treatment accordingly, with the goal of preventing morbidity, mortality, and improving quality of life. Key considerations in the treatment of hyperammonemia include the patient's clinical status, the trend in serum ammonia levels, and the response to nitrogen-scavenger therapy, as well as the availability of dialysis equipment and staff 1.
From the FDA Drug Label
For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma. Controlled studies have shown that lactulose solution therapy reduces the blood ammonia levels by 25 to 50%; The treatment for hyperammonemia is lactulose. It has been shown to reduce blood ammonia levels by 25 to 50% 2.
From the Research
Treatment Options for Hyperammonemia
The treatment for hyperammonemia involves various medications and therapies aimed at reducing ammonia levels in the blood. Some of the treatment options include:
- L-ornithine L-aspartate (LOLA) 3, 4, 5: LOLA has been shown to improve mental status and decrease serum and spinal fluid ammonia levels by stimulating the urea cycle and glutamine synthesis.
- Lactulose 6, 4, 5: Lactulose is a laxative that can help reduce ammonia production in the gut and is often used to treat hepatic encephalopathy.
- Rifaximin 6, 4, 5: Rifaximin is an antibiotic that can help reduce ammonia production in the gut and is often used in combination with lactulose to treat hepatic encephalopathy.
- Probiotics 4, 5: Probiotics can help reduce ammonia production in the gut and may be used in combination with other treatments to manage hyperammonemia.
- L-carnitine 4: L-carnitine may be used in combination with other treatments to manage hyperammonemia.
Mechanisms of Action
The mechanisms of action of these treatments involve:
- Reducing ammonia production in the gut 6
- Stimulating the urea cycle and glutamine synthesis 3
- Enhancing ammonia uptake by small bowel bacteria 6
- Reducing portal pressure and improving liver function 6
Efficacy and Safety
The efficacy and safety of these treatments have been evaluated in various studies, including:
- A systematic review and network meta-analysis that found LOLA, lactulose, and rifaximin to be effective in reducing ammonia levels and improving outcomes in patients with hepatic encephalopathy 4
- A systematic review and network meta-analysis that found rifaximin and lactulose to be most effective for reversal of minimal HE in patients with cirrhosis, and L-ornithine L-aspartate and lactulose to be most effective in preventing overt HE 5