Placental Transfer Of Midazolam And Its Supporting Role In Cesarean Section

OBJECTIVE:To establish an HPLC method for the determination midazolam in maternal vein plasma,umbili-cal vein plasma and umbilical artery plasma. To assess transplacental passage of midazolam by measuring the levels in maternal and umbilical plasma at the time of delivery. we observed the effect of the anxiety response on mothers and the adverse effect on the neonates. To discuss the feasibility of midazolam preoperative application in cesarean section.METHODS:15 ASA physical status I pregnants,having no histroy of operatation, aged 20～35 years old, weighted 65～80 kg of term delivery,scheduled for selective cesarean section under combined spinal-epidural anesthesia. Use midazolam 0.03 mg/kg to assist to be in sedation (group A). After patients entering the operation room,use the anesthetic machine continuous monitoring BP, HR, SPO2, EKG, RR and open lactate Ringer's solution intravenously. After the patients lying on the right, enforce the anesthesia combined epidural way and subarachnoidal way. After the success of puncture L2-3, inject spinal anesthesia solution 2.5ml into the subarachnoid space, and insert the catheter in the epidural cavity. The anesthesia level was controlled to T6. The bed Was put on 15 left lcaning position to prevent from supine hyportensive syndrome. Make the parturient anesthetic plane in stability, and in general good condition, before the start of surgery, use midazolam 0.03 mg/kg with intravenous bolus to assist to be in sedation. Respectively recorded pulse oxygen saturation (SPO2), respiration rate(RR), mean arterial blood pressure(MAP), and heart rate(HR) of the parturient, when before injection (To),5 minutes after injection (T1), skin incision (T2). According to the AVAT and OAA/S standard, record the level of sedation. Blood samples withdrawn from MV, UV, UA before ligature of the cord were studied by HPLC. Randomly selected 15 cases of pregnant women another, with normal combined spinal-epidural Anesthesia for cesarean section (group B). Recorded and compared between two groups of neonatal 5 min after parturition and fetal umbilical venous blood gas analysis during parturition.Results:The linear range of midazolam was 10～1600 ng/ml, r=0.9982 and the limit of detection was 2 ng/ml; The method recovery was 95.5%～108.2%(n=5). Within-day precision was 3.59%～7.61%(n=5), between-day precision was 5.11%～8.24%(n=5). In all patients it took 5～8 min to deliver the fetus. Apgar test scores were high in the 15 neonates. The A group plasma concentration of MV, UV and UA was respectively (68.96±12.19) ng/ml,(42.77±15.66) ng/ml and (31.81±9.08) ng/ml at the time of delivery. Placental transmission of midazolam was(62.02±14.87)%.A group of mothers have received OAA/SⅢ-Ⅳgrade one level of sedation when 5min after injection. After the medicine gaven, A group of mother's SP02 and RR there were did not have obvious changes. When skin incision, A group of maternal MAP, heart rate increased (P<0.05), but lower than B group. No significant diference was seen between the two groups in Apgar and umbilical venous blood gas analysis of newborn infants(P>0.05).Conclusions:The method is convenient and accurate, so it is suitable for the determination of midazolam in human plasma. The low dose midazolam(0.03mg/kg) injected intravenous prior to cesarean is effective to decrease anxiety and stress response from mothers, and not associated with adverse neonatal effects.