BUPIVACAINE TRANSFER ACROSS THE HUMAN TERM PLACENTA - A STUDY USING THE DUAL PERFUSED HUMAN PLACENTAL MODEL

Background: Bupivacaine is widely used for obstetric analgesia, yet pu blished information on the mechanism of human placental bupivacaine tr ansfer is sparse. The dual perfused human placental model was used to elucidate the factors governing the placental transfer of bupivacaine. Methods: Bupivacaine transfer was studied using the recirculating (cl osed) model and the single pass (open) model. Single placental cotyled ons were perfused with either heparinized Krebs-Ringer's buffer (KRB) supplemented with human albumin (fetal and maternal circuits) or 100% fresh frozen plasma (maternal circuit) to control the bupivacaine prot ein binding in those circuits. In the open model, bupivacaine clearanc e was compared before and after being subjected to either increasing c oncentrations of bupivacaine or its structural analog, mepivacaine. Re sults: For those studies in which the maternal and fetal protein bindi ng was equal, the maternal to fetal (M --> F) transfer was significant ly greater (P < 0.05) than that in the fetal to maternal (F --> M) dir ection. When the perfusates were modified to simulate actual in vivo p lasma protein concentrations, bupivacaine transfer was shown to be rel ated to the degree of protein binding found in the two circuits. In th e open studies, bupivacaine transfer was similar at all concentrations investigated, unaffected by mepivacaine, and related to the pH of the fetal perfusate. A concentration effect was seen within the placental tissue at the end of the experiment. Conclusions: Bupivacaine placent al transfer characteristics suggest passive diffusion rather than acti ve drug transport and appear to be influenced by the maternal and feta l plasma protein binding, fetal pH, and placental uptake.