Effects of fetal pH on local anesthetic transfer across the human placenta

Abstract

Background: Fetal acidemia increases umbilical, venous bupivacaine concentrations in the in situ rabbit model. The authors studied the effects of decreasing fetal pH on the rate of maternal to fetal (M→F) clearances of lidocaine, bupivacaine, 2-chloroprocaine, and antipyrine (a nonionic marker of placental transfer) across the isolated, dual perfused, human placental cotyledon. Methods: Maternal to fetal clearances of bupivacaine, lidocaine, 2-chloroprocaine, and antipyrine were determined 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 with in vivo maternal and fetal protein-binding potentials. Results: Placental transfer of all three agents increased linearly as the fetal pH decreased. Antipyrine transfer was unaffected. Clearance of lidocaine and bupivacaine, but not 2- chloroprocaine, returned to baseline when fetal pH was restored to 7.4. When maternal and fetal protein-binding potentials were increased, clearance at fetal pH 7.4 of bupivacaine, but not lidocaine, decreased significantly. 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 proportion of ionized local anesthetic in the academic fetal perfusate and consequent widening of the M→F concentration gradient of the unionized form. Transfer of lidocaine and bupivacaine was limited by the maternal protein binding.