脂肪乳剂对布比卡因中毒犬的血流动力学及药代动力学的影响  

Effects of lipid emulsion on hemodynamics and pharmacokinetics of mongrel dogs with bupivacaineinduced cardiac depression

作　　者：王权光[1] 刘乐[1] 徐旭仲[1] 陈丽梅[1] 陈莺[1] 王万铁[2] 吴辉[1] 

机构地区：[1]温州医学院附属第一医院麻醉科,325000 [2]温州医学院病理生理学教研室

出　　处：《中华医学杂志》2009年第25期1787-1790,共4页National Medical Journal of China

基　　金：浙江省科技计划项目基金（2005C33015）

摘　　要：目的探讨30％脂肪乳剂对布比卡因心脏抑制时血流动力学和药代动力学学影响。方法14只杂种犬随机分为实验组和对照组。犬静脉输入布比卡因，使平均动脉压（MAP）降至基础值的60％，布比卡因心脏抑制的中毒模型造模成功。实验组静脉注射30％脂肪乳剂负荷量3ml／kg，然后10min均速输入3ml／kg脂肪乳剂。对照组以同样速度和容量输入生理盐水。观察两组犬血流动力学各指标变化，在布比卡因停止输注时和停药后240min内采集动脉血，反相高效液相色谱法测定各时间点血药浓度，分析药代动力学参数。结果实验组经30％脂肪乳剂治疗后血压、心率、心输出量均显著上升（P〈0．05），并与对照组比较升高有统计学意义（P〈0．05）；实验组、对照组布比卡因血药浓度曲线下面积AUC（0-4）分别为（192±35）mg·L^-1min^-1和（271±81）mg·L^-1·min^-1，AUC（0-∞）分别为（231±62）mg·L^-1·min^-1和（368±140）mg·L^-1·min^-1；表观分布容积（Vz）（4．5±1．1）L/kg和（3．3±0．9）L／kg。与对照组比较，实验组的AUC（0-t）、AUC（0-∞）下降、Vz增大有统计学意义（P〈0．05）；在停止布比卡因输注后45～240min实验组的布比卡因血浓度低于对照组（P〈0．05）。结论脂肪乳剂改善布比卡因心脏中毒时的血流动力学状态。脂肪乳剂使布比卡因的药物分布改变是解救局麻药中毒的机制之一。Objective To investigate the effects of Intralipid injection on hemodynamics and pharmacodynamics of mongrel dogs with bupivacaine-induced cardiac depression. Methods Fourteen dogs were randomly divided into lntralipid injection group （the experiment group） and normal saline group（ the control group）. 0. 5% bupivacaine was administrated at a constant rate until the mean arterial pressure （MAP） decreased to 60% of the basic value. Intralipid injection was administered in the experiment group. The hemodynamic parameters were recorded and blood samples were taken from femoral artery at 0, 5, 10, 15, 20, 30, 45,60, 90, 120, 180,240 rain after stopping bupivaeaine infusion for determination of plasma concentration by HPLC. The pharmacokinetic parameters were calculated by Drug and Statistics soft version 2. 0. Results After the treatment of Intralipid injection, MAP, CO, HR increased significantly, compared to those of the control group （ P 〈 0. 05 ）. The AUC （0-t） was （ 192±34 ） mg·L^-1·min^-1 versus （ 271 ±81 ） mg·L^-1·min^-1 and the AUC（0-∞） was （231±62） mg·L^-1·min^-1 versus（368±140）mg·L^-1·min^-1 in the experiment group and the control group respectively. Vz （4. 5±1.1 L/kg versus 3.3±0.9 L/kg） of bupivacaine in the experiment group was significantly higher than that in the control group （ P 〈 0. 05 ）. Condusion Intravenous infusion of Intralipid have beneficial effects on the hemodynamics of mongrel dogs with bupivacaine-induced cardiac depression. One of the mechanism of the beneficial effects was probably that Intralipid injection increases the apparent volume of bupivacaine distribution and that decreases blood concentration.

关 键 词：布比卡因 毒性 脂肪乳剂 血流动力学 药代动力学 

分 类 号：R686[医药卫生—骨科学]