Causes: The urea cycle in the liver in which ammonia gets converted to urea is responsible for excretion of waste nitrogen. Hyperammonemia in newborns is most commonly associated with inherited disorders of amino acid and organic acid metabolism. Causes in adults include Reye’s syndrome, liver failure, sepsis especially infections with urea splitting organisms, high dose chemotherapy, drugs (salicyclates, valproate), gastrointestinal bleeding, multiple myeloma, parenteral nutrition and late onset of urea cycle defects. The latter usually presents with episodic encephalopathy precipitated by metabolic stressors like infection, anesthesia or pregnancy.
Clinical features: Hyperammonemia can be life threatening and if persistent can lead to irreversible neuronal damage. It leads to cerebral edema causing progressive encephalopathy. Respiratory alkalosis is common due to central hyperventilation. Severe hyperammonemia can also cause seizures. An MRI brain is usually consistent with hypoxic ischemic encephalopathy
When to start dialysis? There are no published guidelines for when to initiate dialysis in a patient with hyperammonemia due to urea cycle defects. It is commonly indicated if the ammonia blood level is greater than three to four times the upper limit of normal or greater than 200 micromoles/L. Continuous hemodialysis is started with higher flow rates and is the most effective treatment in rapidly reducing ammonia levels. Even though ammonia is osmotically active, the rapid removal of ammonia is not associated with disequilibrium syndrome mainly due to two reasons: First, there is a rapid equilibration of ammonia across the cell membrane. Secondly, the total amount in the blood, even in severe hyperammonemia, is only about 200 micromoles. This contributes less than 1 mosm per liter to total osmolality and therefore, even if it were all removed at once, the change in osmolality is too small to make cause disequilibrium. Contrast this with ammonia levels in the urine which are typically in the millimolar range.
The question remains whether to start dialysis in the setting of acute severe hyperammonemia (levels > 200 micromoles/L) and encephalopathy in adults with liver failure and normal kidney function. I was not able to find any literature on it and would like to know what the practice in other institutions is? I believe since severe hyperammonemia can lead to irreversible brain damage, dialysis should be instituted. See this previous post concerning hyperammonemia in individuals with myeloma.