Neonatal Hyperammonemia: Dialyze, Scavenge, or Both?

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We recently had a string of consults for neonatal hyperammonemia, each managed slightly differently. Hyperammonemia in neonates is a life-threatening emergency that can lead to severe long-term neurologic sequelae if not managed quickly. Though rare, hyperammonemia in the neonatal period is commonly due to inborn errors of metabolism, particularly urea cycle defects. The urea cycle is a multistep process responsible for removal of nitrogen from the bloodstream, and a defect in one of the enzymes can lead to buildup of ammonia which can cause brain damage or death.

Long-term treatment requires the use of nitrogen scavengers, such as sodium benzoate, sodium phenylacetate, and more recently carglumic acid in patients who have specific N-acetylglutamate synthase deficiency as a cause of their defect. In the acute presentation of neonatal hyperammonemia, dialysis remains the standard of care. 

How best to dialyze a neonate with hyperammonemia? The ultimate goal is rapid reduction of ammonia from the bloodstream and sustained clearance once the ammonia level has been brought down. Over the past few decades, HD techniques (either intermittent HD or CRRT) have been preferred over PD due to more rapid ammonia clearance. One approach is to use intermittent HD over a prolonged period (longer than a typical IHD session but not running over 24 hours like CRRT) to bring the ammonia level down quickly and then switch to CRRT to keep clearing ammonia as it is generated. One of the challenges with performing intermittent HD in hyperammonemic neonates, however, is their small body size and large blood flow rates you would need to use to clear ammonia effectively, which increases the risk of hemodynamic instability. Unlike intermittent HD, clearance in CRRT is dependent on dialysate flow rate and thus high-dose CRRT using dialysate flow rates above that which would typically be used in AKI has become more commonplace. This can prevent having to switch dialysis machines during treatment and allows for easy titration of the dialysis flow rate in response to serial measurement of serum ammonia levels.

Another controversial subject is whether or not you treat with nitrogen scavengers, such as sodium benzoate or carglumic acid, during the acute hyperammonemia phase or wait until the ammonia level has been brought down. This is always discussed with the Metabolism team. Though starting a nitrogen scavenger upfront may prevent a significant rebound from ongoing ammoniagenesis, these medications are dialyzable and thus higher IV rates may be required to be effective.

Each institution has its own approach. A good review on the topic and the controversies around dialysis in this setting can be found here. How do you approach hyperammonemia in neonates?