From the Guidelines
Management of high ammonia levels requires prompt intervention with medications like intravenous sodium benzoate and sodium phenylacetate, as well as intravenous L-arginine hydrochloride, to enhance ammonia metabolism and reduce ammonia production. According to the consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy 1, the initial management of hyperammonaemia involves discontinuing all oral feeds and providing adequate calories as intravenous glucose and lipids. The guidelines also recommend maintaining a glucose infusion rate of 8–10 mg/kg/min and providing lipids (0.5 g/kg daily, up to 3 g/kg daily) 1.
For severe cases, intravenous sodium benzoate (maximum dose 12 g daily) and sodium phenylacetate (given over 90 min as bolus then as maintenance over 24 h) may be administered to reduce ammonia production 1. Additionally, intravenous L-arginine hydrochloride (given over 90 min as bolus then as maintenance over 24 h) may be used to enhance ammonia metabolism 1.
Identifying and treating underlying causes is crucial, whether it's liver disease, certain medications, or rare metabolic disorders. Patients should be monitored for neurological symptoms like confusion or lethargy, which may indicate hepatic encephalopathy. Adequate hydration and electrolyte balance must be maintained. For acute, severe elevations, continuous renal replacement therapy or hemodialysis may be necessary 1. Regular monitoring of ammonia levels, along with liver and kidney function tests, helps guide treatment adjustments. The goal is to lower ammonia levels while addressing the underlying condition to prevent recurrence and complications.
Some key points to consider in the management of high ammonia levels include:
- Discontinuing all oral feeds and providing adequate calories as intravenous glucose and lipids
- Maintaining a glucose infusion rate of 8–10 mg/kg/min and providing lipids (0.5 g/kg daily, up to 3 g/kg daily)
- Using intravenous sodium benzoate and sodium phenylacetate to reduce ammonia production
- Using intravenous L-arginine hydrochloride to enhance ammonia metabolism
- Monitoring for neurological symptoms and maintaining adequate hydration and electrolyte balance
- Considering continuous renal replacement therapy or hemodialysis for acute, severe elevations.
It's worth noting that the most recent and highest quality study on this topic is from 2023, which provides guidelines for the management of adult acute and acute-on-chronic liver failure in the ICU 1. However, the study from 2020 provides more specific guidance on the management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy 1.
From the FDA Drug Label
Sodium Phenylacetate and Sodium Benzoate Injection infusion should be started as soon as the diagnosis of hyperammonemia is made. Treatment of hyperammonemia also requires caloric supplementation and restriction of dietary protein. Non-protein calories should be supplied principally as glucose (8 to 10 mg/kg/min) with an intravenous fat emulsion added Attempts should be made to maintain a caloric intake of greater than 80 kcal/kg/day. Hemodialysis should be considered in patients with severe hyperammonemia or who are not responsive to Sodium Phenylacetate and Sodium Benzoate Injection administration
High Ammonia Level Management involves:
- Starting Sodium Phenylacetate and Sodium Benzoate Injection as soon as hyperammonemia is diagnosed
- Providing caloric supplementation and restricting dietary protein
- Supplying non-protein calories as glucose with intravenous fat emulsion
- Maintaining a caloric intake of greater than 80 kcal/kg/day
- Considering hemodialysis in severe cases or non-responsive patients 2 2 Key components of treatment include:
- Sodium Phenylacetate and Sodium Benzoate Injection
- Caloric supplementation
- Dietary protein restriction
- Hemodialysis (if necessary)
From the Research
High Ammonia Level Management
- High ammonia levels can be managed through various treatments, including lactulose, rifaximin, and other medications 3, 4, 5, 6, 7
- Lactulose is a commonly used treatment for hepatic encephalopathy, which is a condition characterized by high ammonia levels in the blood 3, 4, 6
- Rifaximin is another medication that has been shown to be effective in reducing ammonia levels and improving symptoms of hepatic encephalopathy 4
- The combination of lactulose and rifaximin has been shown to be more effective than lactulose alone in treating overt hepatic encephalopathy 4
- Other treatments, such as L-ornithine L-aspartate and probiotics, have also been shown to be effective in improving minimal hepatic encephalopathy and reducing ammonia levels 6
- Levocarnitine and lactulose have been used to treat valproic acid-induced hyperammonemia, but there is no significant difference in the reduction of ammonia levels between these treatments 7
Treatment Options
- Lactulose: effective in treating hepatic encephalopathy and reducing ammonia levels 3, 4, 6
- Rifaximin: effective in reducing ammonia levels and improving symptoms of hepatic encephalopathy 4
- L-ornithine L-aspartate: effective in improving minimal hepatic encephalopathy and reducing ammonia levels 6
- Probiotics: effective in improving minimal hepatic encephalopathy and reducing ammonia levels 6
- Levocarnitine: used to treat valproic acid-induced hyperammonemia, but no significant difference in reduction of ammonia levels compared to lactulose 7
Patient Outcomes
- Patients with overt hepatic encephalopathy who received lactulose and rifaximin had a higher rate of complete reversal of symptoms compared to those who received lactulose alone 4
- Patients with minimal hepatic encephalopathy who received lactulose, probiotics, or L-ornithine L-aspartate had improved symptoms and reduced ammonia levels 6
- Patients with valproic acid-induced hyperammonemia who received levocarnitine, lactulose, or combination therapy had no significant difference in reduction of ammonia levels 7