MORPHINE PHARMACOKINETICS DURING CONTINUOUS-INFUSION OF MORPHINE-SULFATE FOR INFANTS RECEIVING EXTRACORPOREAL MEMBRANE-OXYGENATION

Objectives: To determine a) if serum morphine concentration changes du ring the first 3 hrs of extracorporeal membrane oxygenation (ECMO); an d b) if absorption of morphine onto the membrane oxygenator is respons ible for these changes. Also, morphine clearance during the first 5 da ys of ECMO was studied. Design: Prospective, open-label study with con secutive patient enrollment. Setting: Neonatal intensive care unit at a university-affiliated, children's hospital. Subjects: Eleven neonate s with severe persistent pulmonary hypertension of the newborn receivi ng 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-perfor mance liquid chromatography. Morphine concentrations were no different from baseline at 5 mins, 1 hr, or 3 hrs after beginning ECMO. There w as no significant difference in morphine concentration from samples ta ken immediately proximal and distal to the membrane oxygenator at 5 mi ns, 1 hr, and 3 hrs after the start of ECMO. Morphine clearance was ca lculated an days 1, 3, and 5 of ECMO. The mean value for morphine clea rance 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 se rum morphine concentration and there is no uptake of morphine onto the membrane oxygenator of the ECMO circuit. Morphine clearance for infan ts receiving ECMO is variable.