大鼠静脉输注罗哌卡因与利多卡因混合液的毒性反应

System toxicity of intravenous infusion with mixture of Hdocaine and ropivacaine in rats

目的 探讨罗哌卡因与利多卡因混合应用对中枢神经系统(CNS)和心血管(CV)毒性反应的影响。方法 Wistar大鼠36只,随机分为3组,每组12只。A组静脉注射(ⅳ)0.5％罗哌卡因2mg·ks^(-1)·min^(-1),B组ⅳ 1.0％利多卡因4mg·ks^(-1)·min^1,C组ⅳ 0.5％罗哌卡因2mg·kg^(-1)·min^(-1)+1.0％利多卡因4mg·kg^(-1)·min^(-1)。麻醉及相关操作后持续监测脑电图、心电图、平均动脉压(MAP)。待呼吸、循环稳定20min后,血气分析值正常,记录此时的MAP、心率(HR)作为基础值,输入相应的局麻药。记录出现CNS毒性(SZ)、心律失常(DYS)和心脏停搏(ASYS)三个中毒点的时间、计算输入局麻药累积剂量。在各点采动脉血,用高效液相色谱仪测血浆中局麻药浓度。结果 A组发生SZ、ASYS时罗哌卡因累积剂量大于C组(P<0.05),但发生DYS时差异无显著性。B组发生SZ、DYS、ASYS时利多卡因累积剂量大于C组(P<0.05)。A组发生SZ、DYS、ASYS时罗哌卡因血药浓度与C组比较差异无显著性;B组发生SZ、DYS、ASYS时利多卡因血药浓度与C组比较差异无显著性。结论 0.5％罗哌卡因与1.0％利多卡因混合应用后增加了CNS和CV系统毒性。

Objective To evaluate the effects of lidocaine on CNS-and cardio-toxicity of ropivacaine. Methods Thirty-six male Wistar rats weighing 340-390g were randomized to receive 0.5% ropivacaine 2mg·kg^(-1)·min^(-1)(group A n=12) or 0.5% ropivacaine 2mg·kg^(-1)·min^(-1)+1.0% lidocaine 4.0mg·kg^(-1)·min^(-1) (group B n=12) or 1.0% lidocaine 4.0mg·kg^(-1)·min^(-1)(group C n=12). Anesthesia was induced with 4% isoflurane. The animals were tracheostomized and mechanically ventilated. V_T. was set at 10-12 ml·kg^(-1), RR at 40-55 bpm and I: E at 1: 1.5. PaCO_2 was maintained at 35-45 mm Hg. Lead Ⅱ EKG and fronto-occipital electro-encephalogram were continuously monitored. T(rectal) was maintained at 37-38℃. The femoral vein was cannulated for infusion of local anesthetics and femoral artery for direct BP monitoring and blood sampling. Anesthesia was maintained with 3% isoflurane during cannulation and placement of electrodes. The animals were left undisturbed for 20min. After blood-gas values were confirmed to be normal, local anesthetic infusion was begun. Isoflurane concentration was reduced to 1% during local anesthetic infusion. The intervals between the start of infusion to the onset of seizure activity(SZ), dysrrhythmia(DYS) and asystole (ASYS) were recorded. Arterial blood samples were obtained at the onset of SZ, DYS and ASYS. Plasma concentrations of local anesthetics were determined by high-performance liquid chromatography(HPLC). Results The cumulative doses of repivacaine producing SZ and ASYS in group B were smaller than those in group A(P<0.05), but there was no significant difference in the cumulative doses of ropivacaine at the onset of DYS between group A and B(P>0.05 ). There were no significant differences in the plasma concentrations of ropivacaine at the onset of SZ, DYS and ASYS between group B and A(P>0.05). The durations between the start of infusion to the onset of SZ, DYS and ASYS were longer in group C than in group A(P<0.01). Conclusion Simultaneous 1.0% lidocaine infusion delays the onset of ventricular dysrrhythmin induced by ropivacaine but increases its CNS-and cardio-toxicity.