Phenobarbital Dosing and Pharmacokinetics in a Neonate Receiving Extracorporeal Membrane Oxygenation

OBJECTIVE: To describe the dosing and pharmacokinetics of phenobarbital in a neonate receiving extracorporeal membrane oxygenation (ECMO). CASE SUMMARY: The treatment of a 2.6 kg, 38-week gestational age boy with congenital diaphragmatic hernia who developed seizures while receiving ECMO support is described. A loading dose of 20 mg/kg resulted in concentrations of 16.4 and 12.9 μg/mL at 3 and 24 hours, respectively. A maintenance dose of 5 mg/kg/d provided a peak concentration of 19.7 μg/mL and trough concentration of 16.7 μg/mL after four doses. The calculated volume of distribution was 1.2 L/kg and the estimated elimination half-life was 92 hours. Serum concentrations decreased after circuit changes unless the new circuit was redosed. DISCUSSION: The reported incidence of seizures in neonates while receiving ECMO support is 18%. Despite this frequency, there are no clinical reports describing anticonvulsant use in this population. This case demonstrates the use of standard phenobarbital doses to achieve low, but therapeutic, serum concentrations. Pharmacokinetic analysis revealed a volume of distribution slightly larger than expected in neonates and an elimination half-life similar to published values. Altering circulating blood volumes resulted in significant reductions in serum concentrations. CONCLUSIONS: Neonates on ECMO may have a larger volume of distribution than neonates not receiving ECMO and may require larger phenobarbital doses to achieve desired serum concentrations. This may result from the presence of large exogenous blood volumes for priming, as well as loss of drug during circuit changes, extraction by the circuit, or hemofiltration. Further work is needed to better define the pharmacokinetics and pharmacodynamics of phenobarbital in the neonatal ECMO population.