EXTRACORPOREAL MEMBRANE-OXYGENATION EXPOSES INFANTS TO THE PLASTICIZER, DI(2-ETHYLHEXYL)PHTHALATE

Objectives: To determine the exposure to, and evaluate the potential t oxicity from, the plasticizer, di(2-ethylhexyl)phthalate (DEHP) during extracorporeal membrane oxygenation (ECMO) therapy. Design: Protocol 1 consisted of a prospective comparison of three ECMO circuit designs in vitro. Protocol 2 consisted of a prospective, comparative clinical study evaluating DEHP plasma concentrations in ECMO vs. non-ECMO patie nts with respiratory failure. Setting: Neonatal intensive care unit at The Children's National Medical Center, Washington, DC. Patients: In protocol 2, 28 consecutive term infants were referred for ECMO therapy . Eighteen infants required ECMO; ten control patients received conven tional ventilation and improved without ECMO. Interventions: In protoc ol 1, three ECMO circuit designs were primed in vitro with normal sali ne, albumin, and human blood, which was maintained at 37 degrees C and recirculated at 400 mL/min far 48 hrs. Plasma samples were obtained a t time 0, 1 hr, and every 6 hrs. In protocol 2, ventilatory and cardio vascular management of the patients in the study was conducted by the attending physician. Patients were placed on ECMO when they met the in stitutional criteria far ECMO therapy. Dairy plasma concentrations for DEHP were collected until 3 days after decannulation from bypass in t he ECMO group. Control patients were sampled daily until extubation. E vidence of cardiac, liver, or lung toxicity was evaluated by Chest Rad iographic Scores, liver function studies, and echocardiograms obtained on day 1, day 3, and the day of decannulation in the ECMO group, or a t the time of extubation in the control group. Sedation, blood product transfusions as indicated, antibiotics, and hyperalimentation were ad ministered to all patients. Measurements and Main Results: All DEHP pl asma concentrations were measured by gas chromatography. In protocol 1 , three circuits were studied: circuit A (small surface area); circuit B (larger surface area); and circuit C (surface area of A but with he parin-bonded tubing in the circuit). DEHP leached from circuit A at 0. 32 +/- 0.12 mu g/mL/hr, compared with 0.57 +/- 0.14 mu g/mL/hr from ci rcuit B (p < .05). This amount of DEHP extrapolates in the ECMO patien t to a potential exposure of 20 to 70 times that exposure from other m edical devices or procedures, such as transfusions, dialysis, or short -term cardiopulmonary bypass. Circuit C showed almost no leaching from the circuit; DEHP concentrations decreased at a rate of 0.2 +/- 0.04 mu g/mL/hr. In protocol 2, DEHP was undetected in the control patients . DEHP concentrations in ECMO patients were greater in the early cours e of ECMO. However, most patients cleared this compound from the plasm a before decannulation. In contrast to the in vitro results in protoco l 1, the average highest concentration at any time on bypass was 8.3 /- 5.7 mu g/mL or 2 mg/kg. Conclusions: DEHP teaches from ECMO circuit s, with potential exposure concentrations related to the surface area of the tubing in the ECMO circuit. Heparin bonding of the tubing elimi nates this risk. Although significant concentrations of DEHP leach fro m the nonheparin-bonded circuits over time, our in vivo studies showed that the DEHP plasma concentrations were less than the previously rep orted values and do not correlate with any observable short-term toxic ity. This compound may be either efficiently metabolized by the newbor n, or redistributed into various tissues. Although signs of toxicity w ere not found in this study, long term complications from chronic expo sure to DEHP have not been determined.