Effect of umbilical perfusate pH and controlled maternal hypotension on placental drug transfer in the rabbit.
The purpose of this study was to explore the effect that fetal acidosis and poor maternal placental blood flow may have on the rate of passage across the placenta of drugs commonly used in labor: bupivacaine and meperidine. The rabbit placenta perfused in situ on the fetal side was used, and antipyrine (phenazone) was included as an index of placental exchange and of maternal placental flow. Bupivacaine and meperidine (both 1.25 mg/mL) and antipyrine (4 mg/mL) were infused into a maternal external jugular vein, at 3 mL/h, after loading, in seven anesthetized does. A single placenta in each doe was perfused via the umbilical arteries with Krebs' bicarbonate buffer at pH 7.5 (phase 1), 7.0 (phase 2), and 7.5 (phases 3-5). During phase 4 maternal blood was withdrawn so as to reduce maternal arterial pressure by 35%, and in phase 5 it was reinfused. Concentrations of drugs were measured during each of the five phases in maternal arterial plasma (Cma) and in the effluent perfusate collected from the umbilical vein (Cuv). From these data, placental clearance rates (Cuv x umbilical flow/Cma) were calculated for each drug at each phase. Clearance of bupivacaine and meperidine increased (P less than 0.03) during phase 2, whereas that of antipyrine did not. Clearance of meperidine and antipyrine, but not of bupivacaine, decreased during phase 4. If these results can be extrapolated to the clinical situation, they suggest that the adverse effects of drugs may well be exacerbated in the presence of fetal compromise.