What is the treatment for hyperammonemia?

From the Guidelines

Treatment of high ammonia levels should prioritize addressing the underlying cause, reducing ammonia production, and enhancing its removal from the body, with the primary goal of lowering ammonia levels below 100 μmol/L to prevent cerebral edema and neurological damage. For acute hyperammonemia, the first-line treatment includes stopping protein intake, administering i.v. glucose at an infusion rate of 8–10 mg/kg/min, and i.v. lipids at 0.5 g/kg daily, up to 3 g/kg daily, as recommended by the consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy 1.

• The treatment should also include i.v. sodium benzoate, with a maximum dose of 12 g daily, given over 90 min as a bolus, then as maintenance over 24 h, with dosing based on weight: 250 mg/kg for weight <20 kg, and 5.5 g/m2 for weight >20 kg.
• Additionally, i.v. sodium phenylacetate, i.v. sodium benzoate and sodium phenylacetate, and i.v. l-arginine hydrochloride may be administered, with dosing based on weight and specific deficiencies, as outlined in the guidelines 1. In severe cases, particularly with hepatic encephalopathy or rapidly deteriorating neurological status, coma, or cerebral oedema, initiation of intermittent HD or high-dose CKRT is recommended, with the goal of rapidly reducing ammonia levels 1.
• The choice of dialysis modality should be determined by institutional preference, local facilities, and the patient's specific condition, with consideration of the safety, efficacy, and complications of each type of dialysis.
• Hybrid therapy, combining HD and CKRT, may be used to gradually reduce ammonia levels while controlling the rebound effect, with HD as the first-line KRT modality for rapidly reducing ammonia levels, followed by CKRT to prevent rebound 1. The goal of treatment is to lower ammonia levels below 100 μmol/L, as elevated ammonia can cause cerebral edema and neurological damage through disruption of neurotransmitter systems and astrocyte function, and to improve morbidity, mortality, and quality of life outcomes.

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%; this is generally paralleled by the improvement in the patients’ mental state and by an improvement in EEG patterns.

Treatment of high ammonia can be managed with lactulose (PO) as it reduces blood ammonia levels by 25 to 50% 2.

• The clinical response to lactulose therapy is observed in about 75% of patients.
• Lactulose is used for the treatment of portal-systemic encephalopathy, which is associated with high ammonia levels.

From the Research

Treatment Options for High Ammonia

• The treatment of high ammonia levels, also known as hyperammonemia, depends on the underlying cause of the condition 3, 4, 5.
• In cases of hepatic encephalopathy, administration of L-ornithine L-aspartate (LOLA) has been shown to improve mental status and decrease serum and spinal fluid ammonia levels by stimulating the urea cycle and glutamine synthesis 3.
• Haemodialysis or haemo(dia)filtration is considered the first-line treatment for acute severe hyperammonaemia in adults 6.
• Nutritional and metabolic factors play an important role in the cause and management of hyperammonaemia, and nonhepatic hyperammonaemia causes such as drugs, infection, and inborn errors of metabolism may require specialist investigations and treatment 4.
• In pediatric patients, treatment is mainly aimed at establishing anabolism to avoid endogenous protein breakdown and amino acid imbalances, and pharmacological treatment options exist to improve urea cycle function or remove nitrogen 5.

Key Considerations in Treatment

• Any delay in recognition and start of treatment of hyperammonemia may have deleterious consequences for the patient 5.
• An increased awareness of hyperammonemia and the immediate start of appropriate therapy are crucial to improve the prognosis of acute hyperammonemia 5.
• The approach to testing and key treatment principles may prevent progressive neurological damage and improve outcomes for patients with hyperammonaemia, especially from nonhepatic causes 4.
• In any unexplained change in consciousness or unexplained encephalopathy, hyperammonemia must be excluded as fast as possible 5.