The effects of polyvinyl chloride (PVC) tubing and membrane oxygenator (MO) on the concentrations of lorazepam and morphine in the neonatal extracorporeal membrane oxygenation (ECMO) circuit were evaluated using an in vitro model that included a closed ECMO circuit with a MO, heat exchanger, bladder and PVC tubing. The circuit was primed with blood, electrolytes, albumin and heparin and maintained at physiologic pH and temperature throughout by frequent measurement of blood gas pH and a temperature probe. Lorazepam and morphine were each studied separately in three separate, but identical circuits for 6 h on the day of circuit prime (new circuit) and then again for 6 h at 24 h (old circuit). Each circuit (new and old) was spiked once with lorazepam to a final concentration of 250 ng/mL or with morphine to a final concentration of 70 ng/mL in the circuit. Serial samples were drawn at baseline and every 30-60 min for 6 h at the site of injection and pre- and post-MO for each circuit. Lorazepam and morphine concentrations were analysed using gas chromatography with electron capture and gas chromatography with mass spectrometry, respectively. The concentrations of morphine and lorazepam at various sample sites and time points were expressed as a percentage of the original concentration. This single-dose study shows that up to 50% of a dose of lorazepam and 40% of a dose of morphine may be extracted by PVC and MO during bypass, depending on the age of the circuit. As the circuits become older, this amount could increase. These data may explain, in part, the higher doses of lorazepam and morphine required to sedate patients during ECMO.