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.