老年患者靶控输注瑞芬太尼对丙泊酚药代动力学的影响  

Effect of remifentanil on propofol pharmacokinetics with target controlled infusion in elderly patients

作　　者：许川雅[1] 吴新民[2] 蒋建渝[1] 卢炜[3] 

机构地区：[1]北京大学第三医院麻醉科,北京100191 [2]北京大学第一医院麻醉科 [3]北京大学药学院药剂学系

出　　处：《北京大学学报（医学版）》2010年第6期734-738,共5页Journal of Peking University:Health Sciences

摘　　要：目的:探讨靶控输注(target controlled infusion,TCI)不同血浆浓度和不同时间的瑞芬太尼对老年患者丙泊酚药代动力学的影响。方法:选取32例择期下腹部开腹手术的患者,美国麻醉医师学会(American Society of Anesthesiologists,ASA)Ⅰ～Ⅱ级,年龄65～82岁。随机分为4组,每组8例,A组复合硬膜外麻醉,B组TCI瑞芬太尼血浆浓度4μg/L,C组TCI瑞芬太尼血浆浓度7μg/L,D组TCI瑞芬太尼血浆浓度4μg/L且输注时间大于4h。所有患者均TCI丙泊酚,血浆浓度为3mg/L。术中记录脑电双频指数值(bispetral index,BIS)、心率(heart rate,HR)、桡动脉压等指标。分别于麻醉诱导前、TCI丙泊酚后1、3、5、10、15、30min及以后每30min,停止TCI丙泊酚后即刻、2、4、6、8、10、15、30、45min及1、2、4、6、8、12、24h取桡动脉血,以反相高效液相色谱-荧光法测定丙泊酚的血浆浓度。应用NONMEM软件将A组分别和B、C、D组建立全量回归模型后,将瑞芬太尼作为唯一的固定效应加入最终模型,单独考察瑞芬太尼对老年患者丙泊酚药代动力学的影响。结果:(1)4组患者术中均能维持合理的麻醉深度(BIS值40～60)和稳定的血流动力学。(2)3组(A+B组,A+C组,A+D组)丙泊酚药代动力学最终模型均符合三室开放模型,目标函数值分别为-810.1,-714.4,-896.4。将瑞芬太尼合并用药分别加入3组模型,模型的目标函数未见减小。结论:靶控输注血浆浓度4μg/L、7μg/L的瑞芬太尼以及连续输注血浆浓度4μg/L的瑞芬太尼4h以上对老年患者丙泊酚的药代动力学均没有影响。Objective：To investigate the effects of remifentanil administered by target-controlled infusion （TCI） with different plasma concentration and time on pharmacokinetics of propofol in elderly patients. Methods： Thirty-two ASA Ⅰ-Ⅱ patients （65-82 years old） undergoing elective lower abdo-minal operations were divided into 4 groups randomly： TCI propofol combined with epidural block （group A,n=8）; TCI remifentanil with plasma concentration 4 μg/L and propofol （group B,n=8）; TCI remifentanil with plasma concentration 7 μg/L and propofol （group C,n=8）; and TCI propofol and remifentanil （plasma concentration 4 μg/L） with infusion time longer than 4 hours（group D,n=8）. Propofol was infused by target-controlled infusion with plasma concentration 3 mg/L in the 4 groups. bispetral index（BIS）,heart rate（HR）,blood pressure（BP） were recorded during operation. Blood samples were collection from radial arterial catheter. Samples of 2 mL of arterial blood were taken at 0,1,3,5,10,15,30 min and then every 30 min after the start of the infusion of propofol,and at 0,2,4,6,8,10,15,30,45,60,120,240,360,480,720,1 440 min after the termination of the infusion of propofol. Propofol concentrations in blood were measured by reversed-phase high-performance liquid chromatography （HPLC）. The pharmacokinetics analyses were performed using the nonlinear mixed-effects model approach implemented in NONMEM computer program. After obtaining the best NONMEM model with covariates,the influence of coadministered remifentanil on the model was examined. Results： In all the patients,the depth of anesthesia was enough （BIS value=40-60）,and the circulatory system function was stable during operation. The final model of propofol pharmacokinetics in the three groups （A＋B,A＋C,and A＋D groups） was best described by a three-compartment mammillary model. The values of objective function（OFV） were -810.1,-714.4,and -896.4. Addition of remifentanil covariate effects to the final model resu

关 键 词：二异丙酚 瑞芬太尼 药代动力学 麻醉 静脉 老年人 

分 类 号：R614.24[医药卫生—麻醉学]