From the Guidelines
Elevated ammonia levels, or hyperammonemia, are associated with a high risk of cerebral edema, intracranial hypertension, and hepatic encephalopathy in patients with acute liver failure (ALF). This condition is particularly concerning in ALF patients, as they are more susceptible to these complications due to their inability to cope with hyperammonemia 1. The development of intracranial hypertension and hepatic encephalopathy is strongly linked to ammonia levels, with a significant increase in risk when ammonia levels exceed 200 umol/L 1.
Key Effects of Hyperammonemia
- Cerebral edema: a potentially life-threatening condition characterized by swelling of the brain
- Intracranial hypertension: increased pressure within the skull that can lead to brain damage or death
- Hepatic encephalopathy: a neurological disorder that can cause confusion, altered consciousness, and coma
Management Considerations
- Unlike acute-on-chronic liver failure (ACLF), treatments such as lactulose and rifaximin have not demonstrated benefit in ALF patients with hyperammonemia 1
- Reducing ammonia levels is crucial to preventing cerebral edema and intracranial hypertension
- Addressing the underlying cause of hyperammonemia, such as liver disease, is essential to managing the condition
Clinical Implications
- ALF patients with hyperammonemia require close monitoring for signs of cerebral edema and intracranial hypertension
- Early recognition and treatment of hyperammonemia are critical to improving outcomes in ALF patients 1
- Further research is needed to develop effective treatments for hyperammonemia in ALF patients, as current options are limited 1
From the FDA Drug Label
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. Lactulose causes a decrease in blood ammonia concentration and reduces the degree of portal-systemic encephalopathy.
The effects of elevated ammonia levels (hyperammonemia) include:
- Impaired mental state
- Abnormal EEG patterns
- Portal-systemic encephalopathy, which can progress to hepatic pre-coma and coma 2 Reducing blood ammonia levels can lead to an improvement in these conditions 2
From the Research
Effects of Elevated Ammonia Levels
The effects of elevated ammonia levels, also known as hyperammonemia, can be severe and potentially life-threatening. Some of the key effects include:
- Hepatic encephalopathy, a neuropsychological syndrome caused by biochemical disturbances in brain function in advanced liver disease patients 3, 4
- Altered mental status, which can progress to seizures, coma, and death if left untreated 5, 6, 7
- Cerebral edema, a potentially fatal complication of acute hyperammonemia 6
- Neurological symptoms, such as confusion, agitation, and altered level of consciousness 5, 4
Causes and Diagnosis
Hyperammonemia can be caused by a variety of factors, including:
- Liver disease, such as cirrhosis or portosystemic shunting 3, 6, 4
- Urea cycle disorders, which can be inherited or acquired 5
- Bariatric surgery, which can lead to hyperammonemia-induced encephalopathy in rare cases 5
- Dehydration, which can cause pseudo-hyperammonemia and altered mental status 7 Diagnosis of hyperammonemia typically involves measurement of plasma ammonia levels, although this may not always be reliable or necessary for diagnosis 6, 4
Treatment Options
Treatment of hyperammonemia depends on the underlying cause and severity of the condition. Some common treatment options include:
- Lactulose, which can help reduce ammonia production and absorption in the gastrointestinal tract 3, 5, 4
- Rifaximin, which can be used in combination with lactulose for short-term and long-term treatment of hepatic encephalopathy 3, 4
- Dietary protein restriction, which can help reduce ammonia production in patients with urea cycle disorders 5
- Sodium benzoate, which can be used to treat urea cycle disorders 5
- Intravascular resuscitation, which can be effective in treating dehydration-associated pseudo-hyperammonemia 7