What is hyperammonemia (elevated blood ammonia levels)?

From the Guidelines

Hyperammonemia is a condition characterized by excessive levels of ammonia in the blood, defined as >100 µmol/l (170 µg/dl) in neonates or ≥50 µmol/l (85 µg/dl) in term infants, children, and adolescents, and can be either inherited due to genetic enzyme deficiencies or acquired from liver disease, certain medications, or other medical conditions. This condition occurs when the body cannot properly metabolize and eliminate ammonia, a toxic byproduct of protein breakdown. Symptoms range from mild (confusion, lethargy, vomiting) to severe (seizures, coma, brain damage), depending on ammonia levels and duration of exposure. Treatment typically involves reducing blood ammonia through medications like sodium benzoate, sodium phenylacetate, or lactulose, which help remove ammonia from the body. Dietary protein restriction is often necessary, with specific amounts determined by a healthcare provider based on the severity of the condition. In acute severe cases, hemodialysis may be required to rapidly lower ammonia levels. Hyperammonemia is particularly dangerous because ammonia readily crosses the blood-brain barrier and can cause neurological damage, making prompt diagnosis and treatment essential to prevent permanent brain injury, as supported by the consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy 1.

Key Points

• Hyperammonemia can be inherited or acquired, and symptoms vary depending on ammonia levels and duration of exposure.
• Treatment involves reducing blood ammonia through medications and dietary protein restriction.
• Hemodialysis may be required in acute severe cases to rapidly lower ammonia levels.
• Prompt diagnosis and treatment are essential to prevent permanent brain injury.

Management

• Stop protein intake and provide adequate calories as intravenous glucose and lipids.
• Use nitrogen-scavenging agents like sodium benzoate and sodium phenylacetate.
• Consider hemodialysis or continuous kidney replacement therapy (CKRT) in severe cases.
• CKRT is recommended as the first-line treatment for hyperammonaemia when possible, with a goal of achieving a blood flow rate (Qb) of 30-50 ml/min and a dialysate flow rate (Qd)/Qb >1.5, as supported by the consensus guidelines 1.

Prognosis

• The prognosis of neurological damage depends on the duration of hyperammonaemic coma and plasma ammonia levels.
• Adverse prognostic factors include hyperammonaemic coma lasting >3 days, increased intracranial pressure, and/or a plasma ammonia level >1,000 μmol/l (1,703 μg/dl), as reported in the study 1.

From the Research

Definition of Hyperammonemia

• Hyperammonemia refers to a clinical condition associated with elevated ammonia levels, manifested by a variety of symptoms and signs, including significant central nervous system (CNS) abnormalities 2.
• It is a condition where there is an excess of ammonia in the blood, which can be toxic to the body, particularly the brain 3, 2.

Causes of Hyperammonemia

• Hyperammonemia can result from an inherited or acquired impairment in hepatic detoxification, leading to potentially life-threatening neuropsychiatric symptoms 3.
• It can also occur due to congenital enzymatic deficiencies, environmental causes, or medications that lead to ammonia toxicity 2.
• Liver failure, such as hepatic encephalopathy, is a common cause of hyperammonemia 4, 3.

Symptoms and Effects of Hyperammonemia

• Hyperammonemia can cause a range of symptoms, including neuropsychiatric symptoms, such as altered mental status, and CNS abnormalities 2, 5.
• Elevated ammonia levels can be toxic to the brain and other organs, leading to serious health complications 3, 2.

Treatment of Hyperammonemia

• Treatment of hyperammonemia typically targets the reduction of ammonia levels in the blood, and may involve medications such as lactulose and rifaximin 4, 3.
• Other treatments may include sodium benzoate, which has been shown to reduce ammonia levels in some cases 6.
• In some cases, fluid resuscitation may be beneficial in treating dehydration-associated pseudo-hyperammonemia 5.