靶控输注瑞芬太尼和异丙酚麻醉诱导时镇静催眠效应的相互作用

目的 探讨靶控输注(TCI)瑞芬太尼和异丙酚麻醉诱导时镇静催眠效应的相互作用.方法 择期全麻手术患者32例,ASAⅠ或Ⅱ级,年龄22～63岁,体重指数18～25 kg/m2.采用TCI异丙酚和瑞芬太尼诱导麻醉,随机分为4组(n=8):Ⅰ组单纯TCI异丙酚,Ⅱ组～Ⅳ组TCI瑞芬太尼,血浆靶浓度分别为2、4、6 ng/ml,当瑞芬太尼血浆靶浓度与效应室浓度达平衡时开始TCI异丙酚,异丙酚初始血浆靶浓度均为0.5μg/ml,当异丙酚血浆靶浓度与效应室浓度达平衡时以0.5μg/ml的浓度梯度递增诱导至患者意识消失.每隔3min观察睫毛反射和意识状态,同时抽取桡动脉血样6ml,分别采用反相高效液相色谱法和高效液相色谱-紫外法测定异丙酚和瑞芬太尼血药浓度.采用药效学相互作用模型公式和等辐射法分析两者镇静催眠效应的相互作用.结果 与Ⅰ组比较,Ⅱ组～Ⅳ组睫毛反射消失和意识消失时异丙酚血药浓度降低,而Ⅱ组～Ⅳ组随瑞芬太尼血药浓度升高,异丙酚血药浓度依次降低(P<0.05).睫毛反射消失和意识消失时,异丙酚和瑞芬太尼血药浓度用药效学相互作用模型曲线拟合均优于直线回归(P<0.05).拟合出睫毛反射消失时EC50,prop=2.77μg/ml、EC50,rem=26.67 ng/ml,其等辐射法公式EC prop/2.77+Ecrem/26.67=0.69;意识消失时EC50,prop=3.76μg/ml、EC50,rem=31.56 ng/ml,其等辐射法公式Ecprop/3.76+Ecrem/31.56=0.65.结论 麻醉诱导期间,TCI瑞芬太尼(血浆靶浓度2～6ng/ml)和异丙酚在镇静催眠效应上呈协同作用.

Sedative and hypnotic interaction between propofol and remifentanil by target-controlled infusion during induction of anesthesia

Objective To investigate the sedative and hypnotic interaction between remifentanil and propofol by target-controlled infusion (TCI) during induction of anesthesia.Methods Third-two ASA Ⅰ or Ⅱpatients,aged 22-63 yr,body mass index 18-25 kg/m2,scheduled for elective surgery under general anesthesia,were randomly divided into 4 groups(n=8 each).Group Ⅰ only received TCI pmpofol.GroupⅡ,Ⅲ,and Ⅳreceived a target concentration of 2,4 or 6 ng/ml remifentanil respectively.While the blood-effect site concentrations of remifentanil were equilibrated,patients received TCI of propefol,with an initial target concentration of 0.5μg/ml.After the blood-effect site concentrations of propofol were equilibrated then with 0.5μg/ml increments until the loss consciousness was achieved.The eyelash reflex and state of consciousness were assessed and radial arterial blood sample 6 ml was taken every 3 min to determine the remifentanil and propofol concentrations in blood.Propofol and remifentanil concentrations in blood were measured by reversed-phase high-performance liquid chromatography and high-performance liquid chromatography with ultraviolet detection respectively.The sedative and hypnotic interaction between propofol and remifentanil was determined with a pharmacodynamie interaction model by regression analysis and determined using the isobolographic method.Results Propofol concentrations in blood were lower in group Ⅱ,Ⅲ and Ⅳ than group Ⅰ(P<0.05).The propofol concentratopms in blood were significantly decreased in trun with the increase in the remifentanil concentrations in blood in group Ⅱ-Ⅳ(P<0.05).At loss of eyelash reflex and loss of consciousness of patients,the pharmacodynamic interaction model by curve fitting was superior to linear regression (P<0.05).At loss of eyelash reflex of patients,the curve fitting result showed EC50,prop=2.77μg/ml and EC50,rem=26.67 ng/ml,and the isobolographic method equation is ECprop/2.77+ECrem/26.67=0.69.At loss of consciousness of patients,the curve fitting result showed EC50,prop==3.76μg/ml and EC50,rem=31.56ng/ml,and the isobolographic method equation is Ecprop/3.76+Ecrem/31.56=0.65.Conclusion Remifentanil (Cp 2-6 ng/ml) and propofol by TCI shows a synergistic type of pharmacodynamic interaction on the sedative and hypnotic during induction of anesthesia.