兔颈内动脉不同浓度丙泊酚输注药效学研究

摘要

Objective To study the rabbit EEG inhibition patterns of propofol via intracarotid artery and it's pharmacodynamic characteristics.Methods A total of 25 white rabbits were enrolled in this Dixon sequential study,and each animal received three sets of experiments.The rabbit cerebral state index (CSI) and EEG burst suppression (BS) changes were selected as the monitoring indicators.According to the Dixon sequential method,using 10 mg·kg 1·h 1 as a unit,three different concentrations of propofol (0.33 ％;0.5％; 1％) continuous infused to carotid artery for 10 min.If CSI appeared below 50,and BS above 0,the propofol infusion rate will be reduced to lower level for the next one.If there was no emergence of this state,the infusion rate will be raised in the next one.The changes of Cerebral State Index(CSI),Burst Suppression (BS) and other vital were observed at different time point of study (T1-T5).Probit test was used to calculate EC50 and EC95.Logistic regression analysis was applied to get the propofol concentration-effective probability curve.Results There were minor vital signs changes during experiment among the three groups.CSI values decreased after starting infusion of propofol.Regression analysis of Probit test revealed that EC50 and EC95 for group 0.5％ was the minimum (29.263 mg·kg-1·h-1)in three groups.Conclusion Continuous infusion of different concentrations of propofol via intracarotid artery of rabbits can reach EEG burst suppression depth of anesthesia.Higher concentration of continuous propofol infusion for 10 minutes to reach a certain depth of anesthesia required wide range of delivery speed.The stability of required infusion rate would be improved by reducing drug concentrations.%目的 通过观察不同浓度丙泊酚对脑电的抑制作用,研究颈内动脉持续输注丙泊酚对大脑功能的影响及其药效学特点.方法 25只大耳白兔,每只接受3组实验.兔大脑状态指数(CSI)、脑电爆发抑制(BS)变化为监测指标,按Dixon序贯法,以10 mg·kg-1·h-1为单位,3组不同浓度丙泊酚(0.33％、0.5％、1％)颈内动脉持续输注10 min.阳性标准为CSI＜50并且BS ＞0维持10 min以上.5个不同时点记录兔生命指标和不良反应.序贯资料采用Probit检验,计算EC50和EC95,Logistic回归分析丙泊酚浓度-有效概率曲线.结果 3组实验兔生命体征有所改变,但在可接受范围内.丙泊酚输注开始后CSI均降低,3组变化有所不同,序贯实验Probit检验0.5％组EC50在3组中最低,为29.263 mg·kg-1·h-1,0.33％和1.0％组分别为41.761和31.939mg·kg-1·h-1.EC95 0.5％组在3组中最低.结论 兔颈内动脉持续输注不同浓度丙泊酚可达到脑电爆发抑制的麻醉深度,高浓度丙泊酚持续输注10 min达到一定麻醉深度所需速度范围较广,降低浓度,可提高药物速度变化稳定性,与静脉持续输注相比,降低麻醉药用量而避免药物余量所产生的不良反应.