Morphine pharmacokinetics during continuous infusion of morphine sulfate for infants receiving extracorporeal membrane oxygenation

Objectives: To determine a) if serum morphine concentration changes during the first 3 hrs of extracorporeal membrane oxygenation (ECMO); and b) if absorption of morphine onto the membrane oxygenator is responsible for these changes. Also, morphine clearance during the first 5 days of ECMO was studied. Design: Prospective, open-label study with consecutive patient enrollment. Setting: Neonatal intensive care unit at a university-affiliated, children's hospital. Subjects: Eleven neonates with severe persistent pulmonary hypertension of the newborn receiving continuous intravenous infusions of morphine sulfate and requiring ECMO. Interventions: Blood samples were obtained from the subjects and ECMO circuits at predetermined time intervals. Measurements and Main Results: Serum morphine concentration was determined using high-performance liquid chromatography. Morphine concentrations were no different from baseline at 5 mins, 1 hr, or 3 hrs after beginning ECMO. There was no significant difference in morphine concentration from samples taken immediately proximal and distal to the membrane oxygenator at 5 mins, 1 hr, and 3 hrs after the start of ECMO. Morphine clearance was calculated an days 1, 3, and 5 of ECMO. The mean value for morphine clearance was 11.7 +/- 9.3 (SD) mL/min/kg (range 2.6 to 34.5). Conclusions: The initiation of ECMO does not lead to a significant decrease in serum morphine concentration and there is no uptake of morphine onto the membrane oxygenator of the ECMO circuit. Morphine clearance for infants receiving ECMO is variable.