Phenobarbital use in an infant requiring extracorporeal membrane life support

Over the past two decades, there has been an increased use of extracorporeal membrane life support (ECLS) for critically ill neonates and infants. Approximately 20% of these children will experience seizures as a complication of ECLS or the comorbid condition which necessitated extracorporeal support. While phenobarbital is one of the most common drugs used to treat seizures in children, little is known about its dosing while on ECLS. We present a 3-month-old girl who required ECLS after cardiac arrest in the postoperative period following surgery for complex congenital heart disease. The patient subsequently developed seizure activity, which was treated with phenobarbital. Following an initial loading dose of 30 mg/kg, the serum concentration was 47.9 mcg/ml. A supplementary loading dose of 10 mg/kg was administered 8 h later with an increase of the maintenance dose to 8 mg/kg/day. The phenobarbital serum concentrations were 65.9 and 72.8 mcg/ml on the subsequent days. Despite therapeutic levels of phenobarbital, the patient continued to exhibit clinical and electroencephalographic evidence of seizure activity and a midazolam infusion was started at 0.3 mg/kg/h. Because of continued seizure activity, the patient ultimately required titration of midazolam to 1.2 mg/kg/h by day 7 of ECLS to control seizure activity. Due to severe intracerebral bleeding on day 9, ECLS was withdrawn and the patient expired. Our experience demonstrates some of the challenges of medication titration during ECLS. Previous reports of phenobarbital dosing during ECLS are reviewed and considerations for the dosing of anticonvulsant medications during extracorporeal support are discussed.