Transfer of methohexital across the perfused human placenta

Study Objectives: To evaluate the transfer properties of methohexital and the influence of protein binding using the in vitro human placental perfusion model. Design: Fresh term human placentae from healthy parturients were perfused bidirectionally via a cannulated fetal chorionic artery and vein and needles placed into the maternal intervillous space. Maternal-to-fetal (M→F) and fetal-to-maternal (F→M) transfer and ultimate distribution of methohexital was investigated using a closed (recirculating) placental perfusion model. Setting: Obstetric anesthesia laboratories of two university medical centers. Patients: No patient participation occurred as placentae were obtained after delivery. Intervention: M→F and F→M transfer of methohexital was compared in vitro in perfusates with equal protein concentrations (2 g/100 mL in both perfusates) or albumin-simulated physiologic protein binding concentrations (maternal 8 g/100 mL; fetal 4 g/100 mL). Measurements and Main Results: Data obtained consisted of measurements of methohexital and antipyrine concentrations by high-performance liquid chromatography. Glucose and lactate concentrations and perfusate loss were measured to assess placental viability. Methohexital protein binding was assessed at 2, 4, and 8 g/100 mL of albumin by equilibrium dialysis. The transfer index of 0.83 ± 0.11 for the M→F perfusions was significantly greater ( p ≤ 0.05) than in the F→M direction (0.61 ± 0.04) when albumin concentration was equal in both perfusates. This transfer asymmetry disappeared when albumin concentrations simulating maternal (8 g/100 mL) versus fetal (4 g/100 mL) protein concentrations in the perfusate were used (M→F 0.87 ± 0.12 and F→M 0.95 ± 0.11). Conclusion: Methohexital readily crosses the placenta in both directions. Protein binding has significant effects on the degree of transfer of methohexital at any time when compared with antipyrine and its ultimate fetal/maternal distribution.