Rf. Johnson et al., BUPIVACAINE TRANSFER ACROSS THE HUMAN TERM PLACENTA - A STUDY USING THE DUAL PERFUSED HUMAN PLACENTAL MODEL, Anesthesiology, 82(2), 1995, pp. 459-468
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.