Dialysis in neonates with inborn errors of metabolism

Background. Certain inborn errors of metabolism become manifest during the neonatal period by acute accumulation of neurotoxic metabolites leading to coma and death or irreversible neurological damage. Outcome critically depe nds on the immediate elimination of the accumulated neurotoxins. Recent tec hnological progress provides improved tools to optimize the efficacy of neo natal dialysis. Methods. We report our experience with continuous venovenous haemodialysis (CVVHD) in six neonates with hyperammonaemic coma due to urea-cycle disorde rs or propionic acidaemia and in one child with leucine accumulation due to maple-syrup urine disease (MSUD), in comparison with five patients managed by peritoneal dialysis (PD) (2 hyperammonaemia, 3 MSUD). Application of a new extracorporeal device specifically designed for use in small children p ermitted the establishment of stable blood circuits utilizing small-sized c atheters, and the tight control of balanced dialysate flows over wide flow ranges. Results. Plasma ammonia or leucine levels were reduced by 50% within 7.1+/- 4.1 h by CVVHD and within 17.9+/-12.4 h by PD (P<0.05). Also, total dialysi s time was shorter with CVVHD (25+/-21 h) than with PD (73+/-35 h, P<0.02). A comparison of the CVVHD results with published literature confirmed supe rior metabolite removal compared to PD, and suggested comparable efficacy a s achieved with continuous haemofiltration techniques. Apart from accidenta l pericardial tamponade during catheter insertion in one case, no major com plications were noted with CVVHD. In three of the five PD patients, dialysi s was compromised by mechanical complications. None of the MSUD patients bu t four children with urea-cycle disorders died, two during the acute period and two later during the first year of life, with signs of severe mental d elay. Of the eight children presenting with hyperammonaemic coma, the four with the most rapid dialytic ammonia removal rate (50% reduction in <7 h) s urvived with no or moderate mental retardation, whereas slower toxin remova l was always associated with a lethal outcome. Simulation studies showed th at the efficacy of neonatal CVVHD is limited mainly by blood-flow restricti ons. Conclusions. While CVVHD is the potentially most efficacious dialytic techn ique for treating acute metabolic crises in neonates, utmost care must be t aken to provide an adequately sized vascular access.