Pharmacocinétique de la bupivacaïne administrée par voie péridurale ou sous-arachnoïdienne pour césarienne réglée

Abstract

Twenty ASA 1 pregnant women at term, undergoing elective Caesarean section were included in this study. They were randomly assigned to one of two groups, receiving either a spinal or an epidural anaesthesia. Before induction, in order to prevent hypotension, all patients were given an i.v. infusion of 1000 ml of Ringer-lactacte and a subcutaneous injection of ephedrine 30 mg. They were positionned on the operating table with a 15° left lateral tilt. Spinal anaesthesia was performed with hyperbaric bupivacaine 0.5 p. cent (0.08 mg · cm −1 of height). Epidural anaesthesia was obtained with a bolus dose of 0.5 p. cent plain bupivacaine, followed by a continous infusion through the epidural catheter until the level of surgical block reached T6 bilaterally. Bupivacaine was assayed in plasma by high performance liquid chromatography (HPLC). Following pharmacokinetic parameters of bupivacaine were determined : Cmax (maximal concentration), Tmax (time to reach maximum), AUC (area under curve), Cl (total plasma clearance), Vz (volume of distribution during the elimination phase), T1/2 (elimination half-life). Bupivacaine concentration was also measured in samples obtained at birth from umbilical vein and umbilical artery. The mean dose of bupivacaine used was 12.8 ± 0.6 mg in the spinal group and 118.6 ± 17.8 mg in the epidural group. The time of onset of surgical anaesthesia was significantly shorter with spinal anaesthesia (7.6 ± 4.4 vs 31 ± 11.1 min ; p < 0.01). The sensory block had a longer duration in epidural group (223.2 ± 15 vs 291 ± 13.8 ; p < 0.001). The first demand for postoperative analgesia occurred significantly earlier in spinal than in epidural group (172 ± 101 vs 442 ± 144 min ; p < 0.01). Nevertheless, the total amount of analgesies administered did not differ between the two groups. The number of patients who developed hypotension, as well as the Apgar score and acid-base status of the neonates at birth, were similar in the two groups. There was no significant difference in the quality of analgesia achieved with either spinal or epidural anaesthesia. The degree of maternal satisfaction was evaluated with a visual analogic scale (0–10) and was similar in the two groups. After spinal anaesthesia, the maximal plasma concentration of bupivacaine was significantly lower (p < 0.05) than in the epidural group, where it was close to the threshold of toxicity. The pharmacokinetics of bupivacaine has not been assessed by numerous studies, especially in the case of spinal anaesthesia. In this study, the Tmax in the spinal group was shorter than in the epidural group (p < 0.05), because of continuous epidural administration of bupivacaine. The prolonged elimination half-life of bupivacaine after epidural administration and its significantly lower plasma clearance in the epidural group might result either from the prolongation of absorption after the end of the perfusion or from a non linear absorption kinetics. The confirmation of the latter hypothesis requires further studies in order to determine whether hepatic enzymes which metabolize bupivacaine are susceptible of being fully saturated in some circumstances.