Uptake and Distribution of Bupivacaine in Fetal Lambs

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Abstract
Direct continual measurement of placental drug transfer was introduced to evaluate more precisely the fetal uptake of a commonly used local anesthetic in obstetrics. Bupivacaine, 2.7 mg .cntdot. kg-1 (base), was infused at a constant rate over 1 h into a maternal jugular vein of five chronically prepared pregnant ewes. Blood was sampled simultaneously from the umbilical vein (UV), fetal aorta (FA), and a maternal artery (MA). Fetal uptake rate was determined from the product of the bupivacaine UV-FA blood concentration difference and the umbilical flow rate .ovrhdot.Qu. Total fed accumulation was determined by integrating uptake rate over 5 h. Correlation of total fetal uptake and the infused mean maternal dose (r = 0.993, P < 0.001) indicated that during the infusion, mean fetal uptake was a constant fraction (0.16) of the maternal infused dose. Total fetal uptake was linear despite wide individual changes in .ovrhdot.Qu, suggesting that within limits fetal accumulation is not .ovrhdot.Qu-dependent. Mean ovine protein binding of bupivacaine by maternal and fetal whole blood was 85.49% .+-. 2.61 (SD) and by fetal blood, 40.43% .+-. 9.60 (SD). Back-transfer of bupivacaine to the mother proceeded against a higher total bupivacaine concentration because unbound unionized drug concentrations in maternal blood were less than in fetal blood. At maternal-fetal equilibrium when UV and FA total blood concentrations were equal, the calculated fetal/maternal concentration ratio (f/m) (0.36) determined from the maternal and fetal protein binding and pH closely approximated the observed (0.35). The f/m increased during both fetal uptake and back-transfer and cannot be considered a good index of placental transfer. Back-transfer suggests that following an unintentional intravascular injection, delivery should be delayed for back-transfer to be completed, provided maternal and fetal circulation remain adequate.

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