高原容量控制性失血性休克猪丙泊酚药代动力学研究

发布时间：2018-04-11 11:30

本文选题：高原 + 失血性休克　；参考：《兰州大学》2017年硕士论文

【摘要】：目的:探讨高原环境下容量控制性失血性休克猪体内丙泊酚药代动力学的特点。方法:24头健康长白猪,随机分为4组,分别为休克组(HS组)、对照组(C组)、晶体液复苏组(JR组)、胶体液复苏组(HR组),每组6头。HS组、JR组及HR组在20min内由右侧股动脉放出总血量的30%血液,建立高原(海拔4120米)容量控制性失血性休克模型,稳定30min后,HR组在30min内输入等失血量的羟乙基淀粉;JR组在30min内输入等失血量的复方氯化钠;液体输注结束后时间点四组均静脉泵入丙泊酚150μg·Kg-1·min-1共10min。在开始泵注丙泊酚的1、2、3、4min,停止泵注丙泊酚时,停止泵注丙泊酚后1、2、4、8、15、25、35、50、70、90、120、150和180min抽取动脉血样2ml,采用高效液相-紫外线法(UPLC-UV)测定丙泊酚血浆药物浓度。根据测定的血药浓度计算丙泊酚的消除半衰期(t1/2)、血浆-效应室平衡速率常数(Ke0)、药时曲线面积(AUC)及平均驻留时间(MRT)等药代动力学参数。结果:与C组相比,HS组和JR组各时间点丙泊酚血浆浓度高于C组(P0.05)。HR组丙泊酚血浆浓度在输注开始1min、输注结束4min和输注结束25min有差异(P0.05),其余时间点无明显差异(P0.05);HS和JR组Cmax显著增高(P0.01),HR组Cmax无明显差异(P0.05);HS组和JR组t1/2显著延长(P0.01),HR组无明显变化(P0.05)。C组t1/2为39.91±5.52min,HS组t1/2为74.59±8.61min,较C组延长约1.8倍。与C组相比,HS组和JR组Ke0显著增大(P0.05),HR组无明显差异(P0.05);HS组和JR组AUC显著增大(P0.05),HR组略增大,但无统计学差异(P0.05);HS组和JR组MRT显著延长(P0.01),HR组无明显差异(P0.05)。结论:在高原环境下容量控制性失血性休克猪体内丙泊酚的药代动力学特点是其在体内清除和排泄时间大大延长,血浆-效应室平衡速率常数(Ke0)和药时曲线面积(AUC)增大,药物消除半衰期(t1/2)和体内平均驻留时间(MRT)延长。等量晶体液复苏不足以改善低血容量情况,致使丙泊酚代谢减慢,血药浓度增加,而等量胶体液可以逆转丙泊酚代谢动力学的改变。
[Abstract]:Objective: to investigate the pharmacokinetics of propofol in porcine with volume controlled hemorrhagic shock at high altitude.Methods 24 healthy Landrace pigs were randomly divided into 4 groups.They were shock group (HS group), control group (C group), lens fluid resuscitation group (JR group), colloid fluid resuscitation group (HR group). Each group (6 heads. HS group JR group and HR group) released 30% of the total blood volume from the right femoral artery in 20min.The model of volume controlled hemorrhagic shock at high altitude (4120 m above sea level) was established. After stabilizing 30min, the HR group was treated with 30min, and the hydroxyethyl starch JR group (JR group) was infused with compound sodium chloride with equal amount of blood loss in 30min.The intravenous infusion of propofol 150 渭 g Kg-1 min-1 for 10 mins was performed in the four groups at the time point after liquid infusion.The pharmacokinetic parameters of propofol such as elimination half-life of propofol (t ~ (1 / 2)), plasma-effect ventricular equilibrium rate constant (K _ (0)), drug time curve area (AUC) and mean residence time (MRT) were calculated according to the measured concentration of propofol.Conclusion: the pharmacokinetic characteristics of propofol in pigs with volume-controlled hemorrhagic shock at high altitude are that the clearance and excretion time of propofol in vivo is prolonged, the plasma-effect ventricular equilibrium rate constant (Ke0) and the area of drug time curve are increased.Drug elimination half life (t 1 / 2) and mean residence time (MRT) were prolonged.The resuscitation of the same amount of crystal fluid was not enough to improve the low blood volume, which resulted in the decrease of propofol metabolism and the increase of blood drug concentration, while the same amount of colloid solution could reverse the change of propofol metabolism kinetics.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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