EFFECTS OF FETAL PH ON LOCAL-ANESTHETIC TRANSFER ACROSS THE HUMAN PLACENTA

Background: Fetal acidemia increases umbilical venous bupivacaine conc entrations in the in situ rabbit model. The authors studied the effect s of decreasing fetal pH on the rate of maternal to fetal(M-->F) clear ances of lidocaine, bupivacaine, 2-chloroprocaine, and antipyrine (a n onionic marker of placental transfer) across the isolated, dual perfus ed, human placental cotyledon. Methods: Maternal to fetal clearances o f bupivacaine, lidocaine, 2-chloroprocaine, and antipyrine were determ ined at fetal pH (7.4), during progressive fetal acidemia (pH 7.2-->7. 0-->6.8), and after recovery to fetal pH 7.4 in experiments with both low protein state and in those within vivo maternal and fetal protein- binding potentials, Results: Placental transfer of all three agents in creased linearly as the fetal pH decreased, Antipyrine transfer was un affected. Clearance of lidocaine and bupivacaine, but not 2-chloroproc aine, returned to baseline when fetal pH was restored to 7.4. When mat ernal and fetal protein-binding potentials were increased, clearance a t fetal pH 7.4 of bupivacaine, but not lidocaine, decreased significan tly. During fetal acidemia, the transfer of both agents increased, but to a lesser extent than in the low protein concentration experiments, Conclusions: Increasing the pH difference between maternal and fetal perfusates promotes M-->F passage of unionized lidocaine, bupivacaine, and 2-chloroprocaine. This likely results from an increased proportio n of ionized local anesthetic in the acidemic fetal perfusate and cons equent widening of the M-->F concentration gradient of the unionized f orm, Transfer of lidocaine and bupivacaine was limited by the maternal protein binding.