The Placental Transfer Of Sufentanil: Effects Of Fetal PH, Protein Binding

Objective: Operative anesthesia in the perinatal period has certainparticularity and risks. Effects on the fetus should be considered, though thereis the placental barrier between maternal and fetal, in fact, placenta has littleinfluence of barrier action onto drug transfer, and almost all the medicamentscan enter the fetus through placenta. Therefore, operative anesthesia usinganalgesic on Pregnant women needs to take the inhibitory action to fetus intoaccount. Remifentanil has its particular advantage to be applied in obstetricanesthesia, due to its superiority of exact pain-killing, fast effectiveness andquick eliminating. But studies at home and abroad on its mechanism andfeatures of transfer through placenta, are just not that many. For providingtheoretical basis for remifentanil’s using in obstetric anesthesia, this studyinvestigates factors that affect the placental transfer of China-maderemifentanil, including protein binding,fetal academia using the in vitrohuman placental perfusion model.Methods:18placentas were obtained from healthy mother within10minafter term vaginal or cesarean delivery. Dip them in the cold saline andexamine whether the fetal surface and decidual plate are complete. Pour thebuffer solution by the artery trocar put in the umbilical artery, and meanwhilespray the cold saline on the maternal surface in order to prevent theagglutination of the blood of the placenta. Examine the decidual plate of thematernal surface of placenta, choose a whole well-perfused cotyledon of theplacenta edge, and find the supplying corresponding arteries and veins on thefetal surface to put in pediatric trocar and ligate it, and ligate the brunches ofthe other cotyledons supplied by the same arteries and veins. Cut thecotyledon according to the placenta partition boundary and prevent the lateralleakage by bipolar electrocoagulator. After slowly pour the coldly-heparinized KRB buffer solution into the cotyledon, then watch the lateral leakage of thecotyledon. When there is no lateral leakage, put the well-perfused cotyledoninto the placenta box. With maternal surface upwards and fetal downwards,three No.19blunt needles are inserted into the cotyledon of the depth of2~3mm. Using the constant flow pump as the driving force, At the beginningof each experiment, maternal flow rates were maintained at10-12mL/min,producing perfusate pressures of35-45mmHg. The fetal flow rates(l-3mL/min)were adjusted to provide perfusate pressure of60-75mmHg. The temperatureof the whole experiment is kept in37℃, and pH in7.4±0.05, kept beingmonitored by the pH meter. To test the integrity and viability, glucoseconsumption and lactate production were measured at the end of theexperiments.This experiment is to establish a dual-perfused, single-cotyledon humanplacental model.18placentas are divided randomly into3groups: A is thenormal one, B is of maternal hyporoteinemia, and C is fetal acidemia, with6examples in each. In these18experiments, maternal surface circuits in groupA and C use250ml of fresh frozen plasma to perfuse; fetal surface circuits areperfused with100ml volume of KRB with4g/100ml albumin, but the pH offetal perfusate in group C is adjusted to7.0; in group B, both maternal andfetal circuits use the KRB with2g/100ml albumin to perfuse. Before theexperiment, placenta should be perfused for30min. Put10ng/ml remifentaniland1μg/ml antipyrine into the maternal reservoir when balanced.15min,30min,60min,90min and120min later respectively after finishing addingmedicine into it, draw1ml samples of perfusate from maternal and fetalreservoirs, and then measure the concentration of remifentanil, antipyrine.Finally, calculate the absolute transfer rate and the relative transfer rate.Establish a HPLC/MS/MS method for the determination of theconcentration of remifentanil and antipyrine. Glucose consumption andproducing amount of lactic acid are measured by the biochemical analyzer.Result: remifentanil can cross the placenta rapidly. Its absolute transferrate increases as the time passes and the three groups are not obviously differed. Meanwhile the relative transfer rates of the remifentanil are also notobviously differed(the groupB and the group C are both higher than the groupA). The lactic acid formation rates and glucose consumption of the threegroups are all in the normal range.Conclusion: the establishment and application of the dual perfused ofsingle cotyledon human placenta models can be used to provide theoreticalbasis for transport of medicine through placenta. China-made remifentanil inthe experiment of the dual perfused of single cotyledon in vitro humanplacenta, shows that it can cross the placenta fast, and the absolute transferrate increase as the time passes. When the maternal is in hypoproteinemia orthe fetal acidemia situation, the transfer rate of the placenta of the remifentanilincreases.