Extracorporeal removal of toxic valproic acid levels in children

Toxic ingestion of valproic acid is difficult to treat as no antidote exists and hemodialysis has been considered ineffective for clearance due to high protein binding of this drug. Recent reports suggest that protein binding of valproic acid is saturated at toxic levels, thereby allowing for removal of free drug by extracorporeal circuits. We describe our experiences in two children with toxic blood levels of valproic acid, in whom we were able to achieve effective clearances by extracorporeal removal without charcoal hemoperfusion. In an 18-year-old girl with initial valproic acid levels of 663 μg/ml (therapeutic 46-88 μg/ml), the elimination constant (k_e1) increased five- to eightfold from 0.04/h pre dialysis and 0.06/h post dialysis to 0.31/h during high-flux hemodiafiltration. In the same time periods, drug half-life reduced from 15.96 h pre dialysis and 21 h post dialysis to 2.23 h during hemodiafiltration. In a younger 18-month-old child with initial levels of 922 μg/ml, k_e1 was fivefold higher at 0.25/h during conventional hemodialysis, compared with 0.05/h after dialysis. Similarly, the drug half-life was 2.9 h during dialysis and 12.9 h after dialysis. Both conventional hemodialysis and high-flux hemodiafiltration are effective treatment modalities that should be offered to all pediatric patients with valproic acid ingestion and neurological compromise.