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

• Published in: Anesthesiology (Philadelphia) 1996-09, Vol.85 (3), p.608-615
• Main Authors: JOHNSON, R. F, HERMAN, N. L, JOHNSON, H. V, ARNEY, T. L, PASCHALL, R. L, DOWNING, J. W
• Format: Article
• Language: English
• Subjects: Anesthetics, Local - pharmacokinetics; Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; Biological Transport; Female; Fetus - metabolism; Humans; Hydrogen-Ion Concentration; Medical sciences; Neuropharmacology; Permeability; Pharmacology. Drug treatments; Placenta - metabolism; Pregnancy; Protein Binding; Rabbits
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-199609000-00021

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. 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. 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. 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 acidemic 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.