Uptake and Distribution of Bupivacaine in Fetal Lambs

Autor: Dinesh Doshi, M. J. Kennedy, Richard R. Miller, Roland L. Kennedy, Hansel deSousa, Yadin David, D. L. Heald, J. U. Bell
Rok vydání: 1986
Předmět:
Zdroj: Anesthesiology. 65:247-253
ISSN: 0003-3022
DOI: 10.1097/00000542-198609000-00002
Popis: 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 X 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 (Qu). Total fetal 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 less than 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 Qu, suggesting that within limits fetal accumulation is not 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Databáze: OpenAIRE