Feto‐maternal distribution of epidural drugs used in obstetric analgesia and anesthesia

Abstract

Due to the potential fetal exposure of drugs used in regional epidural block for labor analgesia and cesarean section anesthesia it is important to understand the factors governing the transplacental transfer of these drugs. Published information on the feto‐maternal distribution of the commonly used local anesthetics (lidocaine and bupivacaine) as well as new drugs such as ropivacaine and the alpha‐2 agonists (clonidine and dex‐medetomidine), however, is sparse.A dual‐perfused human placental cotyledon model was established to evaluate the transplacental transfer of two local anesthetics (lidocaine and bupivacaine) and alpha‐2 agonists (clonidine and dexmedetomidine) in vitro. The feto‐maternal distribution of local anesthetics was also studied in vivo after epidural administration for elective cesarean section. Healthy term parturients scheduled for elective cesarean section were randomly allocated in a double‐blinded manner to receive either ropivacaine or bupivacaine. Similarly, another group of parturients was randomized to receive either bupivacaine or lidocaine‐epinephrine through a lumbar epidural catheter.During in vitro placental perfusion, the highly lipophilic bupivacaine and dexmedetomidine were rapidly cleared from the maternal circulation but appeared in low concentrations in the fetal circulation. Conversely, lidocaine and clonidine were cleared less rapidly from the maternal circulation and appeared in higher concentrations in the fetal circulation than did bupivacaine or dexmedetomidine. Substantial amounts of dexmedetomidine were found in the perfused placental cotyledon. In a clinical study after the epidural administration of equal doses of either ropivacaine or bupivacaine, the maternal venous, the umbilical venous and the arterial free drug concentrations of ropivacaine at delivery were approximately twice as high as those for the more lipophilic bupivacaine. The maternal plasma clearance of free bupivacaine was significantly higher than that of ropivacaine. After the epidural administration of lidocaine‐epinephrine or bupivacaine, the fetal/maternal concentration ratios, the total amount of drug retained in the placenta as well as the areas under the concentration versus time curves per unit of dose were similar with a higher incidence of maternal hypotension in the lidocaine‐epinephrine group for cesarean section.The in vitro human placental perfusion method proved to be a useful method for the study of the transplacental distribution of drugs used in parturients. Both in vivo and in vitro, the rapid clearance of highly lipophilic drugs from the maternal circulation, thereby lowering their maternal concentrations, restricted their transplacental transfer to the fetal circulation. This can likely be explained by their higher maternal volume of distribution, and was associated with their uptake into the placental tissue in vitro. Maternal hemodynamics seem to be an important determinant of transplacental drug transfer during epidural anesthesia, probably through their effect on the maternal distribution of drugs. This study indicates that bupivacaine leads to a lower fetal drug exposure compared to lidocaine or ropivacaine. Similarly, according to the perfusion study, dexmedetomidine leads to a lower fetal drug exposure compared to clonidine.