What causes confusion in hyperammonemia and how is it treated?

From the Guidelines

Elevated ammonia levels should be treated with lactulose and rifaximin as first-line medications to reduce ammonia production and absorption. The treatment of elevated ammonia levels, also known as hyperammonemia, is crucial to prevent confusion, altered mental status, and other neurological complications. According to the most recent and highest quality study 1, lactulose is the most studied treatment for reducing ammonia levels and improving cognitive function.

Treatment Approaches

• Lactulose (typical dose 20-30g orally every 4-6 hours) traps ammonia in the intestines, reducing its absorption into the bloodstream 1.
• Rifaximin (550mg twice daily) is an antibiotic that reduces ammonia-producing bacteria in the gut 1.
• For severe cases, intravenous L-ornithine L-aspartate (LOLA) may be used to enhance ammonia metabolism 1.
• Protein restriction in the diet (limiting to 0.5-0.8g/kg/day initially) helps reduce ammonia production 1.
• In emergency situations with severe encephalopathy, hemodialysis or continuous renal replacement therapy may be necessary to rapidly remove ammonia 1.

Monitoring and Adjustments

Regular monitoring of ammonia levels and mental status is crucial during treatment to ensure improvement and adjust therapy as needed 1. Patients should avoid medications that can worsen ammonia levels, including certain diuretics and sedatives. Treating underlying causes, particularly liver disease, is essential to prevent hyperammonemia.

Underlying Causes

The most common cause of hyperammonemia is liver disease, and treating this underlying condition is crucial to prevent further episodes of elevated ammonia levels 1. Other causes, such as urea cycle disorders, should also be addressed and managed accordingly 1.

From the FDA Drug Label

Sodium Phenylacetate and Sodium Benzoate Injection is indicated as adjunctive therapy in pediatric and adult patients for the treatment of acute hyperammonemia and associated encephalopathy in patients with deficiencies in enzymes of the urea cycle During acute hyperammonemic episodes, arginine supplementation, caloric supplementation, dietary protein restriction, hemodialysis, and other ammonia lowering therapies should be considered Hemodialysis should be considered in patients with severe hyperammonemia or who are not responsive to Sodium Phenylacetate and Sodium Benzoate Injection administration High levels of ammonia can be reduced quickly when Sodium Phenylacetate and Sodium Benzoate Injection is used with hemodialysis, as the ammonia-scavenging of Sodium Phenylacetate and Sodium Benzoate Injection suppresses the production of ammonia from catabolism of endogenous protein and hemodialysis eliminates the ammonia and ammonia conjugates

Elevated ammonia can cause confusion and other neurological symptoms.

• The treatment for elevated ammonia includes:
  • Sodium Phenylacetate and Sodium Benzoate Injection
  • Arginine supplementation
  • Caloric supplementation
  • Dietary protein restriction
  • Hemodialysis
• Hemodialysis is recommended for patients with severe hyperammonemia or those who are not responsive to Sodium Phenylacetate and Sodium Benzoate Injection administration 2, 2, 2

From the Research

Elevated Ammonia and Confusion

• Elevated ammonia levels can cause confusion, as well as other neurological symptoms such as seizures or encephalopathy 3, 4, 5.
• Hyperammonemia can be caused by various factors, including liver cirrhosis, inborn errors of metabolism, and certain medications 4, 5, 6.

Treatment of Elevated Ammonia

• Treatment for hyperammonemia typically involves reducing ammonia production and increasing ammonia removal 7, 5, 6.
• Lactulose and rifaximin are commonly used to treat hyperammonemia by reducing ammonia production and absorption in the gastrointestinal tract 4, 7.
• In severe cases, extracorporeal therapies such as haemodialysis or haemo(dia)filtration may be necessary to remove ammonia from the blood 3, 6.
• Fluid bolus and maintenance fluid may also be effective in treating dehydration-associated pseudo-hyperammonemia 4.
• In pediatric patients, management of hyperammonemia includes identification of precipitating factors, reduction of ammonia production, and ammonia removal with pharmacologic treatment or extracorporeal therapies 6.