丙泊酚及靶控输注系统

TCI and Propofol(丙泊酚及靶控输注系统),Steven Shafer (史蒂文宪佛)Editor-in-Chief, Anesthesia & Analgesia (总编辑，麻醉与镇痛)Professor of Anesthesia, Stanford University (麻醉教授, 斯坦福大学),Ive consulted for propofol(我为丙泊酚做过顾问) AstraZenecaIve consulted for remifentanil(我为瑞芬太尼做顾问)Glaxo, AbbottIve consulted for companies interested in TCI(我为对靶控输注系统感兴趣的公司顾问)Alaris, B Braun, Medex,Conflict of Interest(利益冲突),Pharmacokinetic Concepts(药代动力学概念),Volume of Distribution(分布容积),容积,数额,Clearance(清除率),血浆,新陈代谢器官,清除 =药物完全被去除所需的血浆流速,Half-Life(半衰期),The time required for drug concentrations to decrease by 50%.(药物浓度降低50所需的时间),三室模型,单次给药后的时程（分钟）,0,120,240,360,480,600,浓度,1,10,100,中间,慢,迅速,Opioid Half-Lives (minutes)(鴉片類製劑的半衰期 -分钟),半衰期,芬太尼,阿芬太尼,舒芬太尼,迅速,1,1,1,中间,19,13,23,慢,475,111,562,Opioid Pharmacokinetics(鴉片類製劑药代动力学),单次给药后的时程（分钟）,0,120,240,360,480,600,阿片药物浓度占峰值浓度的百分比,0.1,1,10,100,芬太尼,舒芬太尼,阿芬太尼,Context-Sensitive Half-Time(时效相关半衰期),浓度降低50所需的时间（分钟）,单次给药后的时程（分钟）,0,30,60,90,120,0,120,240,360,480,600,芬太尼,阿芬太尼,舒芬太尼,Propofol Pharmacokinetics(丙泊酚 药代动力学),50% effect site decrement curves(效应部位浓度50%衰减曲线),0,120,240,360,480,600,0,30,60,90,120,芬太尼,阿芬太尼,舒芬太尼,瑞芬太尼,0,120,240,360,480,600,0,30,60,90,120,咪唑安定,硫噴妥鈉,丙泊酚,浓度降低50所需的时间（分钟）,静脉输注时间,Propofol/opioid vs. isoflurane/opioid(丙泊酚/鴉片類製劑 vs.异氟醚/鴉片類製劑),清醒所需时间,麻醉时间,5067丙泊酚减少量,6080异氟醚减少量,0,30,60,90,120,0,120,240,360,480,600,Duration of Anesthesia,Minutes Required for Emergence,丙泊酚 药代动力学,Schnider et al, Anesthesiology 1998;88:1170-82,Target Controlled Infusion靶控输注系统,TCI Solves the Differential Equations for Drug Concentration (靶控输注系统解决了药物浓度的微分方程),First Generation TCI(第一代靶控输注系统)Target = Plasma(以血浆为靶部位),CATIA: 第一靶控输注系统 (Schwilden et al, Bonn),“Diprifusor” 第一商业靶控输注系统 ,TCI Variability(靶控输注系统的变异性),Biological variability exists(生物变异性的存在)TCI devices cannot increase biological variability(靶控输注系统不增加生物变异性),TCI Can Reduce Variability(靶控输注系统能减少变异性),TCI removes time as a confounding variable between the device setting and the patient response(靶控输注系统去除了时间这一存在于设备设置和病人反应之间的混杂变量)TCI can incorporate patient covariates to individualize drug dosing(靶控输注系统可以结合个体因素，实施个体化给药):Weight, height, gender, ethnicity (体重, 身高， 性别, 种族)Diseases (疾病)Drug interactions (药物之间相互作用)Pharmacogenetics (药物基因组学),Second Generation TCI(第二代 靶控输注系统)Target = Effect Site(效应部位为靶部位),STANPUMP 靶控输注系统(Shafer, Stanford),0,10,20,30,40,50,60,0,2,4,6,8,10,Fentanyl TCI, Plasma Target(芬太尼TCI，血浆为靶浓度),芬太尼浓度,(ng/ml),唤醒患者,缝皮,稳态,调整剂量,切皮,等待,术前,诱导,血浆,时间(分钟),Three compartment model with effect site(三室模型与效应部位),I,V,2,k,12,V,1,k,13,V,3,迅速平均室,k,21,中央室,k,31,迅速平均室,k,10,效应部位,V,e,静脉注射,k,1e,k,e0,Fentanyl TCI, Plasma Target(芬太尼TCI，血浆靶浓度),芬太尼浓度,(ng/ml),唤醒患者,0,10,20,30,40,50,60,0,2,4,6,8,10,效应部位,血浆,时间(分钟),缝皮,稳态,调整剂量,切皮,等待,术前,诱导,0,10,20,30,40,50,60,0,2,4,6,8,10,30,40,效应部位,Fentanyl TCI, Effect Site Target(芬太尼TCI，效应部位靶浓度),芬太尼浓度,(ng/ml),唤醒患者,血浆,时间(分钟),缝皮,稳态,调整剂量,切皮,诱导,0,10,20,30,40,50,60,0,2,4,6,Propofol TCI, Plasma Target(丙泊酚TCI，血浆靶浓度),丙泊酚浓度,(mcg/ml),唤醒患者,时间(分钟),缝皮,稳态,调整剂量,切皮,等待,术前,诱导,0,10,20,30,40,50,60,0,2,4,6,丙泊酚浓度,唤醒患者,时间(分钟),Propofol TCI, Effect Site Target(丙泊酚TCI，效应部位靶浓度),(mcg/ml),缝皮,稳态,调整剂量,切皮,等待,术前,诱导,Are Drug Models Predictiveof Drug Effect?(药物模型能预测药物效应吗?),Conscious/Unconscious Prediction (Pk)(意识清楚/无意识的预测),Glass et al, Anesthesiology 86:836-847, 1997,Agent (n),BIS,Target,浓度,Measured,丙泊酚 (399),0.976*,0.936,0.937,异氟醚(70),0.959,0.965,0.967,咪唑安定 (50),0.885,0.859,0.886,Significantly different from Pk value for Target Concentration (p 0.001),and Measured concentration (p 0.01),浓度,Are drug models predictive?(药物模型有预测性吗?),Mathematical models of drug behavior incorporating effect site concentrations and drug interactions predict anesthetic drug effect (e.g., loss of response to stimulation) as well as:(结合了效应部位浓度和药物相互作用的药物行为学数学模型可以用来预测药物的效应(例如, 对刺激反应的丧失)，如同下列指标:Measured concentrationsBISAAI（Auditory Evoked Potential）,Third Generation TCI靶控输注系统Closed Loop Effect Site Control(闭合回路 效应部位 控制),RUGLOOP(De Smet, Struys,Ghent),Closed Loop Control of Propofol(闭合回路控制丙泊酚),Struys et al, Anesthesiology. 95:6-17, 2001,BIS,Systolic,Heart Rate,closed-loop controlclassic-control 闭合回路控制 标准控制,Over 500 peer-reviewed articles in Medline as of September 2006(至2006 年9月，Medline有超过500篇相关的同行评论文章)Approved everywhere except in the US(除美国以外均可使用),全世界应用靶控输注系统,UKIRELANDBELGIUMFRANCENORWAYSWEDENDENMARKNETHERLANDSGERMANYAUSTRIA,BRAZILCHILEPERUCOLUMBIAMEXICOVENEZUELAARGENTINASPAINPORTUGALITALYCANADA,PHILLIPINESHONG KONGSINGAPOREAUSTRALIANEW ZEALANDPOLANDHUNGARYBULGARIAJAPANCHINA,世界使用靶控输注系统,药量指南,丙泊酚/瑞芬太尼,TIVA丙泊酚 3-5 g/ml瑞芬太尼 2-6 ng/mlTIVAN氧化亚氮: 65-70%丙泊酚 at 2.5-3.5 g/ml瑞芬太尼 at 2-6 ng/ml,Thank You,Professor Shuren LiPresident, Chinese Society of AnesthesiologistsProfessor Yun YueProfessor and Chairman, Beijing Chaoyang HospitalDr. Yugua