Effects of neonatal extracorporeal membrane oxygenation circuits on drug disposition

Background: It has been observed that neonatal patients receiving extracorp oreal membrane oxygenation (ECMO) require larger doses of sedatives than do non-ECMO patients to achieve similar levels of sedation, Objective: The purpose of this study was to determine whether drug disposit ion of midazolam and morphine, 2 commonly used sedatives, are affected by t he ECMO circuit. Methods: This was a 3-part study. First, a retrospective analysis of prescr iption charts for 10 ECMO neonates and 10 neonates who had undergone cardia c surgery was conducted to confirm that the former group required larger do ses of sedatives. Second, uptake of midazolam and morphine by the polyvinyl chloride (PVC) and silicone components of the neonatal ECMO circuits was ev aluated in vitro. Third, known concentrations of midazolam mere injected in to a complete neonatal ECMO circuit and analyzed after the oxygenator to de termine the effects of the circuit components on the bioavailability of mid azolam, Results: Mean +/- SD total dose of midazolam for the ECMO neonates was 21,2 83 +/- 10,446 mug versus 9599 +/- 5504 pg for the cardiac surgery group (P = 0.008), Mean +/- SD total dose of morphine for the ECMO neonates was 2364 +/- 1280 mug versus 1158 +/- 457 mug for the cardiac surgery group (P = 0. 017), There was significant uptake (68%) of midazolam by the PVC and silico ne components of neonatal ECMO circuits, whereas morphine uptake of 16% was observes only during contact with the PVC component. After 40 minutes of r unning a new ECMO circuit, the concentration of midazolam leaving the circu it was <50% of that injected, Conclusions: There is significant interaction between the PVC and silicone components of an ECMO circuit and the sedative drugs that pass through them . These interactions may affect the bioavailability of these drugs and henc e the doses required to induce a therapeutic effect.