In Response.

Abstract

We thank Drs Kinoshita and Kawahito1 for their interest in, and comments on, our study.1,2 We would like to point out that our cell culture study was not designed to mirror or simulate clinical conditions. To examine specific molecular signaling pathways that ropivacaine may impact in human umbilical vein endothelial cells (HUVECs) and human placental trophoblasts (HPTs), we aimed for a local anesthetic (LA) concentration that would elicit a robust, standardized response while still maintaining cell vitality. In regards to the dose–response curve that we performed (reflecting ropivacaine cytotoxicity), we indeed used rather high LA concentrations for our pharmacological investigations. As we acknowledged in the main article, the drug concentrations used might not be equivalent to the in vivo situation on a cellular level, but they were well suited for our investigations—which is supported by the fact that the observed effects could be blunted by the addition of dexamethasone (ie, signal specificity). As is common in molecular biology experimentation, it is a routine practice to focus on the unbound substances (as opposed to the protein-bound substances, which tend not to elicit an effect on the target cells). Moreover, when discussing the effect of epidural LA dosages on plasma and cellular concentrations (eg, on a placental cellular level), the authors want to point out that there is no definitively proven concentration-dependent relationship between ropivacaine and epidural-related maternal fever. That aside, many intraindividual factors might also influence the plasma concentrations of LA and the activation of the immune system by cellular responses (including genetic factors). It is still unknown why 15%–20% of women in labor receiving epidural anesthesia develop sterile fever—when the other 80%–85% are spared this reaction, despite receiving comparable LA dosages. This warrants further clinical investigation and experimental studies, which may help to yield insights into related causative mechanisms. We hope that the results of our study will stimulate the awareness of, and interest in researching, possible triggers of epidural-related maternal fever. Peter Wohlrab, MDStefan Boehme, MDKlaus U. Klein, MDVerena Tretter, PhD, DIDepartment of AnesthesiaGeneral Intensive Care and Pain ManagementMedical University ViennaVienna, Austria[email protected]