丙泊酚丙泊酚TCI个性化实施探讨个性化实施探讨华中科技大学附属协和医院王 洁TCI概念及原理概念及原理概念概念 靶控输注（靶控输注（TCI）是以药代动力）是以药代动力学和药效动力学原理为基础，以血浆学和药效动力学原理为基础，以血浆或效应室的药物浓度为指标，由计算或效应室的药物浓度为指标，由计算机控制药物输注速率的变化，达到按机控制药物输注速率的变化，达到按临床需要调节麻醉的目的。临床需要调节麻醉的目的。 原理原理丙泊酚三室模型丙泊酚三室模型l以血浆或效应室的靶浓度为调控指标而不是以给以血浆或效应室的靶浓度为调控指标而不是以给药总量或速率为调控指标药总量或速率为调控指标l给药后计算机屏幕实时显示目标血药浓度、效应给药后计算机屏幕实时显示目标血药浓度、效应室浓度、给药时间和累积剂量等室浓度、给药时间和累积剂量等l麻醉医师可以像转动挥发器那样方便地控制静脉麻醉医师可以像转动挥发器那样方便地控制静脉麻醉，提高静脉麻醉控制水平麻醉，提高静脉麻醉控制水平 TCI原理原理麻麻醉醉医医生生从从计计算算药药物物剂剂量量或或输输注注速度中解脱出来速度中解脱出来血血药药浓浓度度迅迅速速达达到到所所需需要要的的浓浓度度或药效或药效计算机控制维持稳定的血药浓度。计算机控制维持稳定的血药浓度。 TCI的优势的优势理想的理想的TCI麻醉麻醉u麻醉诱导迅速麻醉诱导迅速u术中镇痛充分，镇静适中术中镇痛充分，镇静适中u术后最短的苏醒时间术后最短的苏醒时间u确保无术中知晓确保无术中知晓u术后镇痛充分术后镇痛充分u全程完善的个体化给药全程完善的个体化给药1.没有理想的镇痛监测指标没有理想的镇痛监测指标2.意识消失的丙泊酚效应室浓度意识消失的丙泊酚效应室浓度个体差异有个体差异有6倍倍3.药物靶浓度与药代动力学模型药物靶浓度与药代动力学模型推算浓度差推算浓度差30%4.BIS等脑电监测抗干扰性能差等脑电监测抗干扰性能差TCI尚存在的问题尚存在的问题问题导致的后果问题导致的后果麻醉诱导麻醉诱导：用异丙酚和阿片类药物，将：用异丙酚和阿片类药物，将BIS值维持在值维持在5060之间，患者对气管插管有之间，患者对气管插管有意识反应意识反应 4060是人群均值，部分人群是人群均值，部分人群BIS值高于值高于60意识消失，部分人群意识消失，部分人群BIS值低于值低于40对对疼痛刺疼痛刺激激有内隐记忆。有内隐记忆。 临床实践中的问题临床实践中的问题在诱导中丙泊酚和瑞芬的靶浓度如何在诱导中丙泊酚和瑞芬的靶浓度如何选择？选择？在麻醉维持中调节丙泊酚靶浓度时有在麻醉维持中调节丙泊酚靶浓度时有没有最低和最高浓度的限制？没有最低和最高浓度的限制？什什么么时时候候该该调调节节镇镇静静药药(丙丙泊泊酚酚)，什什么时候该调节镇痛药么时候该调节镇痛药(如瑞芬如瑞芬)？麻麻醉醉医医生生如如何何同同时时调调节节丙丙泊泊酚酚和和阿阿片片类药靶浓度以保持平稳麻醉类药靶浓度以保持平稳麻醉? 麻醉医生高质量的完成麻麻醉医生高质量的完成麻醉必须会思考醉必须会思考临床应用问题焦点：临床应用问题焦点：丙泊酚丙泊酚TCI靶浓度的个体化靶浓度的个体化麻醉辅助镇痛药物对丙泊酚麻醉辅助镇痛药物对丙泊酚TCI靶靶浓度有何影响？浓度有何影响？Stepwise丙泊酚丙泊酚TCI靶浓度麻醉诱导靶浓度麻醉诱导意识消失的丙泊酚个体效应室浓度意识消失的丙泊酚个体效应室浓度（OAA/S评分为评分为1分）作为镇静深度的判分）作为镇静深度的判断指标，指导丙泊酚用量断指标，指导丙泊酚用量 术中丙泊酚术中丙泊酚TCI靶浓度不低于该浓度靶浓度不低于该浓度丙泊酚个体化靶浓度丙泊酚个体化靶浓度OAA/S评分评分个体化指标，不可能发生术中知晓个体化指标，不可能发生术中知晓 对镇静深度可作出迅速判断，浓度定对镇静深度可作出迅速判断，浓度定值的变化标志着个体对丙泊酚药物敏值的变化标志着个体对丙泊酚药物敏感度，通过它可直接调节麻醉深浅和感度，通过它可直接调节麻醉深浅和丙泊酚用量。丙泊酚用量。 简单可行简单可行 丙泊酚个体化靶浓度优点丙泊酚个体化靶浓度优点个体化丙泊酚靶浓度麻醉 Anaesthetic stability significantly improved (0.43 +/- 0.44 vs. 1.31 +/- 0.78 丙泊酚每小时调节次数, P = 0.003) Time to extubation was significantly shorter (9.6 +/- 2.1 vs. 15.7 +/- 9.6 min P = 0.011). With FM-TCI, propofol consumption was significantly lower. Eur J Anaesthesiol. 2008 Sep;25(9):741-7镇痛药物与丙泊酚镇痛药物与丙泊酚TCIFuture applications for TCI systemsAmong currently available analgesic drugs, alfentanil and remifentanil are considered to be the most suitable for administration by target controlled infusionAnaesthesia. 1998 Apr;53 Suppl 1:56-60.1.短效镇痛药物瑞米芬太尼大剂量副作短效镇痛药物瑞米芬太尼大剂量副作用明显用明显2.大剂量阿片类药物镇痛封顶效应大剂量阿片类药物镇痛封顶效应3.大剂量瑞米芬太尼麻醉苏醒后疼痛反大剂量瑞米芬太尼麻醉苏醒后疼痛反跳跳瑞芬太尼瑞芬太尼Anaesthesist. 2010 Feb;59(2):126-34.不同瑞芬浓度对丙泊酚TCI靶浓度影响RESULTS: Narcotrend, D(2)/E(0)u 0.2, 0.4, or 0.6 microg/kg remifentanil propofol concentration was 3.02+/-0.86, 1.93+/-0.53 and 1.60+/-0.55 microg/ml respectively uWomen had a higher propofol consumption than men. 瑞芬太尼vs芬太尼RESULTS: Patients in group R exhibited a faster recovery. The incidence of nausea and vomiting was similar in the 2 groups.There was a reduction in the amount of propofol used in group R Minerva Anestesiol. 2006 May;72(5):309-19Propofol and sufentanil for gynecological laparoscopic surgery.RESULTS: Sufentanil (0.2 ng/ml) skin incision(EC(50) ) and (EC(95) ) were 2.2 and 3.7 microg/ml, respectively. The predicted propofol EC(50) and EC(95) to maintain adequate were 2.6 microg/ml ( 2.3-2.7 microg/ml) and 3.6 microg/ml (3.3-4.0 microg/ml), respectively Acta Anaesthesiol Scand. 2011 Jan;55(1):110-7Ketamine effect on bispectral index during propofol-remifentanil anaesthesia.RESULTS: 0.2 mg kg(-1) ketamine administered over a 5 min period did not increase the BIS value over the next 15 min.0.5 mg kg(-1) is associated with an increase in the bispectral index (BIS) values that can lead to an overdose of hypnotic agents Br J Anaesth. 2009 Mar;102(3):336-9 Dexmedetomidine on the adjuvant propofol requirement and intraoperative hemodynamics.RESULTS: The propofol infusion rate was significantly lower in the DEX group than in group C (63.9 16.2 vs. 96.4 10.0 g/kg/min, respectively; P 0.001). The changes in MAP% at T-induction, T-trachea and T-incision in group DEX (-10.0 3.9%, -9.4 4.6% and -11.2 6.3%, respectively) were significantly less than those in group C (-27.6 13.9%, -21.7 17.1%, and -25.1 14.1%; P 0.05, respectively)Korean J Anesthesiol. 2012 Feb;62(2):113-8 Dexmedetomidine on bispectral index understepwise propofol target-controlled infusion.RESULTS: loading dose of dexmedetomidine of 1.0 gkg(-1), not 0.5 gkg(-1) or less, over 10 min followed by 0.5 gkg(-1)h(-1) can definitely decrease the BIS under stepwise propofolPharmacology. 2013;91(1-2):1-6 Interaction of propofol and dexmedetomidine during esophagogastroduodenoscopy in children.RESULTS: The EC50 +/- SE values in the control and DEX groups were 3.7 +/- 0.4 microg x ml(-1) and 3.5 +/- 0.2 microg x ml(-1), respectively. There was no significant shift in the propofol concentration-response curve in the presence of 1 microg x kg(-1)dexmedetomidine.Paediatr Anaesth. 2009 Feb;19(2):138-44.ketamine - propofol, fentanyl - propofol andbutorphanol-propofol on LMA insertion.RESULTS: total dose of propofol required in Group PK was 160.37 15.75mg, in Group PF 156.22 17.18 mg and in Group PB 140.08 18.97 mg.butorphanol to propofol provided absolute jaw relaxation and excellent insertion conditions with stable haemodynamics Side effects like coughing, gagging, lacrimation and laryngospasm were lower.J Anaesthesiol Clin Pharmacol. 2011 Jan;27(1):74-8.初步结果（靶效浓度）：初步结果（靶效浓度）：诱导浓度诱导浓度 麻醉维持浓度麻醉维持浓度 清醒浓度清醒浓度 0.4-0.5 2.5-3.2 1.2-1.5 0.5-0.7 3.0-3.5 1.3-1.7 0.7-1.0 3.1-3.9 1.5-1.9TCI输注浓度人群个性化浓输注浓度人群个性化浓度分布尚在研究中。度分布尚在研究中。谢谢聆听！谢谢聆听！