[摘要]  目的  评价瑞芬太尼Minto药代动力学参数靶控输注（TCI）的效能，并探讨异丙酚持续静脉泵注对老年患者瑞芬太尼靶控输注效能的影响。方法  30例择期手术老年患者，ASAⅠ或II级，年龄65～75岁，体重50～71㎏，随机分为R组和RP组。两组都给予瑞芬太尼（血浆靶浓度5ng·ml^-1）靶控输注30min;RP组在瑞芬太尼TCI同时复合异丙酚（5mg·kg^-1·h^-1）持续静脉泵注。实验过程中维持瑞芬太尼的靶浓度和异丙酚的输注速率不变。桡动脉穿刺进行BP监测和采集血样，锁骨下静脉穿刺进行药品和液体输注。实验过程中连续监测BIS值、MAP、HR、SpO₂ ，TCI开始后1、3、5、10、15、20、25、30min采集桡动脉血，用高效液相色谱法测定瑞芬太尼血浆药物浓度。计算执行误差(PE)、PE的中位数(MDPE)、PE绝对值的中位数(MDAPE)及摆动度来评价TCI系统的性能。结果 R组MDPE、MDAPE、Wobble分别为 －16.8％、23.9％和11.3％；RP组病人的MDPE、MDAPE、Wobble分别为－15.5％、21.7％和10.7％，组间比较差异无统计学意义（P>0.05）。两组瑞芬太尼血药浓度组内及组间比较差异无统计学意义（P>0.05）；与靶浓度相比，两组瑞芬太尼实测血药浓度均显著降低（P<0.05）。结论  瑞芬太尼TCI系统（Minto药代参数）用于国人老年患者可满足临床要求，异丙酚（5mg·kg^-1·h^-1）持续泵注对瑞芬太尼TCI系统效能无影响。

[关键词] 二异丙酚;哌啶类；老年人;药物释放系统  

The influence of Propofol on the effect of target controlld remifentanil infusion in elderly patients

ZHANG Wei,LI Zhi-Song，ZHANG Si,et al. Department of Anesthesiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou  450052, China

【Abstract】  Objective   To evalutate the performance of the target controlled infusion（TCI）system of remifentanil using pharmacokinetic parameters reported by Minto for Chinese old patients and investigate the influence of continuos propofol infusion on TCI of remifentanil.Methods thirty ASAⅠorⅡpatients aged 65～75yr, weighted 50～71kg,undergoing surgery were included in this study.they were randomly divided into group R and RP. remifentanil (plasma concentration) 5ng·ml^-1 was given by TCI in each group and propofol （5mg·kg^-1·h^-1）was continous infused in group RP simultaneously. Remifentanil plasma target concentration and propofol infusion rate were not changed during experiment.radial atery was cannulated for BP monitoring and blood sampling.subclavian vein was cannulated for drug and fluid administration.BIS,MAP,HR and SPO₂ were continuosly monitored during the experiment. Arterial blood samples were taken at 1，3，5，10，15，20，25，30min after TCI for determination of actual blood concentration of remifentanil by High Performance Liquid Chromarography（Waters600）. The performance error(PE) was caculated for each measured blood remifentanil concentration. The performance were caculated by the median performance error（MDPE），the median absolute performance error（MDAPE）and wobble(the median absolute deviation of each PE from the MDPE). Results  The MDPE,MDAPE and Wobble of the remifentanil TCI device in elderly patients（parameter described by Minto ）were -16.8％ 、23.9％ and 11.3％ in group R -15.5％、21.7％and 10.7％ in group RP expectively，There were no significant diferences between the two groups（P>0.05）; The measured remifentanil concentrations were no significant diferences within and between the two groups（P>0.05）.Compaired with predicted target remifentanil concentration ,the measured concentrations of remifentanil were significantly lower in the two groups （P<0.05）. Conclusion  The  performance of Minto parameters is clinically acceptable in Chinese elderly patients;Propofol（5mg·kg^-1·h^-1）doesn’t have an influence on the remifentanil TCI system.

【key words】Propofol ;Piperidines; Aged; Drug delivery system; System performance

近年来，瑞芬太尼靶控输注（TCI）技术已广泛用于临床麻醉，国内瑞芬太尼TCI系统常采用西方人群瑞芬太尼Minto群体药代动力学参数,用于国人老年患者其TCI系统的效能有待进一步评价。异丙酚和哌啶类麻醉性镇痛药是常用的药物组合，研究表明异丙酚和瑞芬太尼药代动力学存在相互作用^[1]，异丙酚对老年患者瑞芬太尼靶控系统的效能有无影响，尚不清楚。本研究拟评价瑞芬太尼Minto药代动力学参数用于老年患者TCI系统的准确性，并探讨异丙酚静脉泵入对老年患者瑞芬太尼TCI系统效能的影响，为老年患者瑞芬太尼TCI的合理应用提供理论依据。

资料与方法

病例选择及分组 老年择期手术患者30例，ASAⅠ或Ⅱ级，年龄65~75岁，体重50~71kg，体重均在标准体重〔标准体重（kg）=身高（cm）－100〕的±15以内。随机分为R组和RP组,各15例。无严重心肺疾患病史和肝、肾及凝血功能障碍。本研究得到医院伦理委员会同意和患者本人同意并签字。

试验方法  所有患者均未用术前药，病人入室后局麻下右锁骨下静脉穿刺，置入双腔导管，用于药物持续泵注和/或靶控输注，局麻下桡动脉穿刺置管，开放内踝静脉后于试验开始前30min内输入林格氏液10ml·kg^-1, 之后按4-2-1法则持续输注。瑞芬太尼（批号：050401, 湖北宜昌人福药业有限责任公司）血浆靶浓度设定为5ng·ml^-1，R组病人用TCI-Ⅰ型泵（北京思路高科技发展有限公司，瑞芬太尼M into模块）靶控输注瑞芬太尼30min ；RP组病人瑞芬太尼靶控输注同时以5mg·kg^-1·h^-1的速率持续泵入异丙酚（批号：BF477,  AstraZeneca公司，英国）30min。连续监测BIS、MAP、HR、SpO₂，面罩辅助呼吸使SpO₂不低于90％。

瑞芬太尼血药浓度测定  TCI开始后1、3、5、10、15、20、25、30min分别采集桡动脉血2ml,加入50％枸橼酸40μl，转入肝素抗凝试管，置于－70℃冰箱保存。采用Waters 600HPLC配二极管阵列紫外检测器（Waters公司，美国 ）测定瑞芬太尼血浆浓度，应用内标法测定瑞芬太尼血药浓度，检测方法见文献^[2]。

TCI系统性能的评价   用执行误差(PE) 、偏离度[以中位数执行误差（MDPE）来表示]、精确度[以中位数执行误差绝对值（MDAPE）来表示]、摆动度（Wobble）评估瑞芬太尼TCI系统性能。计算公式: PE%=(Cm­－Cp)/Cp×100；MDPE=M{PEij；j=1…,Ni}；MDAPE=M{|PE|ij j=1,…,Ni}；Wobble = M {|PEij－MDPEij|,j=1,…,Ni}。

统计学处理 采用SPSS12.0软件进行统计分析，非正态分布的计量资料以中位数（10％分位数，90％分位数）[M (X10％,X90％)]表示，采用Kruskal-Wallis H检验；计量资料以均数±标准差（