Transfer of methohexital across the perfused human placenta

Study Objectives: To evaluate the transfer properties of methohexital and t he influence of protein binding using the in vitro human placental perfusio n model. Design: Fresh term human placentae from healthy parturients were perfused b idirectionally 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 methohexita l runs investigated using a closed (recirculating) placental perfusion mode l. Setting: Obstetric anesthesia laboratories of two university medical center s. Patients: No patient participation occurred as placentae were obtained afte r delivery. Intervention: M-->F alzd F-->M transfer of methohexital was compared in vit ro in perfusates with equal protein concentrations (2 g/100 mt in both perf usates) or albumin-simulated physiologic protein Binding concentrations (ma ternal 8 g/100 mL; fetal 4 g/100 mL). Measurements and Main Results: Data obtained consisted of measurements of m ethohexital and antipyrine concentrations by high-performance liquid chroma tography. Glucose and lactate concentrations and perfusate loss were measur ed to assess placental viability. Methohexital protein binding was assessed at 2, 4, and 8 g/100 mL of albumin by equilibrium. The transfer index of 0 .83 +/- 0.11 for the M-->F perfusions was significantly greater (p less tha n or equal to 0.05) than in the F-->m direction (0. 61 +/- 0. 04) when albu min concentration runs equal in both perfusates. This transfer asymmetry di sappeared when albumin concentrations simulating maternal (8 g/100 mL) vers us fetal (4 g/100 mL) protein concentrations in the perfusate were used (M- ->F 0.87 +/- 0.12 and F-->M 0.5 +/- 0.11). Conclusion: Methohexital readily crosses the placenta in both directions. P rotein binding has significant effects on the degree of transfer of methohe xital at any time when compared with antipyrine and its ultimate fetal/mate rnal distribution. (C) 2000 by Elsevier Science Inc.