低温对失血性休克猪罗库溴铵药代动力学的影响

Effect of hypothermia on pharmacokinetics of rocuronium in pigs with hemorrhagic shock

目的评价低温对失血性休克猪罗库溴铵药代动力学的影响。方法巴马小型猪32头，4—6月龄，雌雄不拘，体重22～25kg，采用随机数字表法分为4组（n=8）：常温对照组（NC组）、常温＋失血性休克组（NH组）、低温对照组（HC组）和低温＋失血性休克组（HH组）。NC组和NH组置于常温环境中，HC组和HH组置于低温（-15℃）冰柜中。NC组和HC组待实验动物清醒后，耳缘静脉注射罗库溴铵3．78mg／kg；NH组和HH组采用容量控制法建立失血性休克模型，于15min内将40％血容量（按30ml／kg计算）经右股动脉匀速放出，于造模成功后30min时经耳缘静脉注射罗库溴铵3．78mg／kg。注射罗库溴铵后即刻（T0）、2min（T1）、4min（T2）、7min（T3）、10min（T4）、15min（T5）、20min（T6）、30min（T7）、60min（T8）、120min（T9）、180min（T10）、240min（T11）和300min（T12）时，采集颈内静脉血样，采用高效液相色谱-二级质谱联用法测定罗库溴铵血药浓度，并计算罗库溴铵最大药物浓度（Cmax）、消除半衰期（t1/2）、血浆-效应室平衡速率常数（Ke0）、药时曲线下面积和平均驻留时间（MRT）。结果与NC组比较，NH组T5～T12时罗库溴铵血药浓度降低，HC组T5-T12时罗库溴铵血药浓度增加，NH组和HC组t1/2延长，Ke0减小，MRT延长（P〈0．05或0．01）；与HC组比较，HH组T4～T12时罗库溴铵血药浓度升高，t1/2延长，Ke0减小，MRT延长（P〈0．05）；与NH组比较，HH组T5～T11时罗库溴铵血药浓度升高，t1/2延长，Ke0减小，MRT延长（P〈0．05）。结论低温可减缓失血性休克猪罗库溴铵的代谢。

Objective To evaluate the effect of hypothermia on the pharmacokineties of rocuronium in the pigs with hemorrhagic shock. Methods Thirty-two Bama mini pigs of both sexes, aged 4-6 months, weighing 22-25 kg, were randomly divided into 4 groups （ n = 8 each） using a random number table： normal temperature control group （group NC） , normal temperature＋hemorrhagic shock group （group NH）, hypothermia control group （group HC）, and hypothermia＋hemorrhagic shock group （group HH）. NC and NH groups were put in the normal temperature environment, and HC and HH groups were put in a freezer at -15 ℃. In NC and HC groups, rocuronium 3.78 mg/kg was injected via the auricular vein after the animals were awake. In NH and HH groups, hemorrhagic shock was then induced by removing 40% of blood volume from the right femoral artery at a constant speed within 15 min （30 ml/kg） , and rocuronium 3.78 mg/kg was injected via the auricular vein at 30 min after the model was successfully established. At 0 （T0）, 2 （T1）, 4 （T2）, 7 （T3）, 10 （T4）, 15 （T5）, 20 （T6）, 30 （T7）, 60 （T8）, 120 （T9）, 180 （T10）, 240 （T11 ） and 300 min （T12） after roeuronium injection, blood samples were collected from the internal jugular vein for determination of the blood concentration of rocuronium by high performance liquid chromatography-tandem mass spectrometry method. The maximum concentration （ Cmax） , elimination half-life （t1/2）, plasma effect-site equilibration rate content （Ko0）, area under concentration curve, and mean residence time （MRT） of rocuronium were calculated. Results Compared with group NC, the blood concentration of rocuronium was significantly decreased at T5-T12 in group NH, the blood concentration of rocuronium was significantly increased at T5-T12 in group HC, and t1/2 was significantly prolonged, Ke0 was decreased, and MRT was prolonged in NH and HC groups （P〈0.05 or 0.01）. Compared with group HC, the blood concentration of rocuronium was significantly increased at T4-T12, t1/2 was prolonged, Ke0 was decreased, and MRT was prolonged in group HH （P〈0.05）. Compared with group NH, the blood concentration of rocuronium was significantly increased at T5-T11, t1/2 was prolonged, Koo was decreased, and MRT was prolonged in group HH （P〈 0.05）. Conclusion Hypothermia can reduce the pharmacokinetics of rocuronium in the pigs with hemorrhagic shock.