右美托咪啶在心外科应用

右美托咪啶在心外科应用阜外医院SICU张永辉心外科患者体外循环or非体外循环先天性心脏病：房间隔缺损，室间隔缺损，法洛四联症等心脏瓣膜病，瓣膜成形或置换术后冠状动脉旁路移植术后主动脉置换介入手术，先天性心脏病介入封堵、主动脉腔内支架、经皮主动脉瓣置换，经皮瓣膜球囊扩张或成形背景心外科术后并发症发生率30.1%显著增加住院时间，死亡率和费用常见并发症：谵妄，感染，急性肾功能不全，心脑血管事件（短暂的脑卒中，昏迷，围术期心梗，心脏传导阻滞和心跳骤停等）负性心脏事件，占所有并发症的50%以上原因：多因素，最为重要的是麻醉、手术、体外循环引起的急性应激，体内儿茶酚胺类激素分泌增多，心脏氧供氧需失调右美托咪啶，镇痛，抗焦虑，抑制中枢交感兴奋传出，调整心脏氧供氧需平衡，抑制儿茶酚胺类释放，稳定血流动力学状态但其抑制交感的作用同时存在负性肌力作用，引起心率慢，低血压等不良事件在心脏外科围术期的使用需要把握适应症，指证和方法镇静镇痛之外-抑制炎症反应High-mobilitygroupbox1高迁移率族蛋白1，非染色体核蛋白稳定核小体结构和调控基因转录诱导TNF-a,IL-1,IL-6产生1lg.kg1for10minafteraorticcross-clamping,and0.5lg.kg1.h1intra-operatively降低高迁移率族蛋白1和白介素水平抑全身炎症反应和器官功能障碍的重要指标制炎症因子表达，发挥器官保护作用Ueki,M.,etal.(2014).Theeffectsofdexmedetomidineoninflammatorymediatorsaftercardiopulmonarybypass.Anaesthesia69(7):693-700.镇静镇痛之外-改善微循环•receiveeitherdexmedetomidine(0.2-1.5μg/kg/h)orpropofol(5-50μg/kg/min)•atICUadmission(baseline[T1])and4hours(T2)and24hoursafterICUadmission(T3)•perfusedsmallvesseldensityandtheDeBackerscorefrombaselineweresignificantlygreaterinthedexmedetomidinegroup•medianchangesinsmall-vesseldensityandtheproportionofperfusedsmallvesselsfrombaselinealsotendedtobehigherinthedexmedetomidinegroupcoLiu,X.,etal.(2016).DexmedetomidineVersusPropofolSedationImprovesSublingualMicrocirculationAfterCardiacSurgery:ARandomizedControlledTrial.JCardiothoracVascAnesth30(6):1509-1515.艾贝宁在对心外科病人可能的获益微创介入手术麻醉清醒镇静镇痛，降低机械通气时间，缩短ICU滞留时间和住院时间预防和治疗谵妄抗交感，降低室速，交界性心动过速等快速心律失常发生率抑制炎症因子释放，脏器保护作用降低死亡率和并发症发生率？介入手术麻醉•监护下的清醒麻醉•免于气管插管全身麻醉•便于术中发现房室传导阻滞•降低呼吸系统并发症发生率•缩短手术时间、住院时间，治疗费用Gallego-Ligorit,L.,etal.(2018).UseofDexmedetomidineinCardiothoracicandVascularAnesthesia.JCardiothoracVascAnesth32(3):1426-1438.减少机械通气时间机械通气患者理想的镇静目标：降低不适感，无躁动，焦虑，最小的血流动力学影响，轻度镇痛长期机械通气危害，呼吸机相关性肺损伤，肺部感染，费用，死亡率增加右美托咪啶可实施清醒镇静镇痛，无呼吸抑制，低血压发生率低于丙泊酚和芬太尼shortertimetoextubation，hazardratio=1.63,95%CI=1.21-2.19,P=0.001).减少4.18hours机械通气时间(95%CI-6.69to-1.67；P＜0.001）Zhang,X.,etal.(2015).Dexmedetomidine:areviewofapplicationsforcardiacsurgeryduringperioperativeperiod.JAnesth29(1):102-111.Liu,X.,etal.(2016).DexmedetomidineVersusPropofolSedationImprovesSublingualMicrocirculationAfterCardiacSurgery:ARandomizedControlledTrial.JCardiothoracVascAnesth30(6):1509-1515.Chuich,T.,etal.(2018).PerioperativeSedationinMechanicallyVentilatedCardiacSurgeryPatientsWithDexmedetomidine-BasedVersusPropofol-BasedRegimens.AnnPharmacother:1060028018793254.缩短ICU滞留时间减少ICU滞留时间anaverage9.89hourreductioninICULOS(95%CI-18.60to-1.19hours;p-value0.03)TheCIdidnotincludezero,thereforetheuseofdexmedetomidinecouldresultinatleasta1.19-hourreductioninICULOS.Nguyen,J.andN.Nacpil(2018).Effectivenessofdexmedetomidineversuspropofolonextubationtimes,lengthofstayandmortalityratesinadultcardiacsurgerypatients:asystematicreviewandmeta-analysis.JBIDatabaseSystemRevImplementRep16(5):1220-1239.缩短住院时间缩短住院时间anaverage37.9-hourreductioninoverallhospitalLOS(95%CI-60.41hoursto-15.46hours;p-value0.00)TheCIdidnotincludezero,meaningtheuseofdexmedetomidinecouldresultinatleasta15.46hourreductioninoverallhospitalLOS.Nguyen,J.andN.Nacpil(2018).Effectivenessofdexmedetomidineversuspropofolonextubationtimes,lengthofstayandmortalityratesinadultcardiacsurgerypatients:asystematicreviewandmeta-analysis.JBIDatabaseSystemRevImplementRep16(5):1220-1239.预防和治疗谵妄心外科术后谵妄发生率20~50%增加术后死亡率，并发症发生率，延长ICU滞留时间和住院时间远期认知功能障碍受损谵妄原因：伽马氨基丁酸受体抑制剂，抗胆碱药物，神经递质紊乱，麻醉，睡眠剥夺、低氧血症，炎症反应非药物性预防措施有效，如早期活动，改善睡眠，增加对时间和地点的识别右美托咪啶显著降低心脏外科术后谵妄发生率，降低54%(riskratio0.46,95%confidenceinterval0.34to0.62;P0.00001)缩短谵妄持续时间，未见统计学差异夜间使用右美托咪啶，能够降低睡眠中断，维持良好睡眠节律机制：不同用于丙泊酚，苯二氮卓类以及其它γ氨基丁酸激抑制剂，不干涉生理性睡眠形式可减少阿片类药物使用量，吗啡增加谵妄发生无呼吸抑制抑制炎症反应Wu,M.,etal.(2018).Perioperativedexmedetomidinereducesdeliriumaftercardiacsurgery:Ameta-analysisofrandomizedcontrolledtrials.JClinAnesth50:33-42.抗心律失常作用心外科术后心律失常发生率40–50%原因：低氧，缺血，损伤，儿茶酚胺和电解质异常交感神经异常兴奋是主要原因降低室性心律失常发生(1%vs5%，P=0.005)减少室速室颤76%交界性心动过速ORof0.328[CI95%0.21;0.51],P0.0001原因：抗交感作用，降低心肌氧耗，减少缺血抑制窦房结活动减慢房室结传导增加迷走神经兴奋性Ling,X.,etal.(2018).Doesdexmedetomidinehaveanantiarrhythmiceffectoncardiacpatients?Ameta-analysisofrandomizedcontrolledtrials.PLoSOne13(3):e0193303.抗心律失常-房颤心脏术后房性心律失常最为常见术后房颤，死亡率增加1倍以上降低房颤发生率，结论不一致有病例对照研究提示保护作用alowerriskofhavingatrialarrhythmias(OR0.74(95%CI:0.60,0.91;P=0.004)postoperativeatrialfibrillationwaslowerinthedexmedetomidinegroup(OR:0.53;95%CI:0.31to0.90,P=0.02)Meta分析阴性结论AFcomparedwiththeplacebo(riskratio[RR]0.76,95%CI0.37,1.55,P=0.44)andmorphinegroups(RR0.86,95%CI0.56,1.31,P=0.48).haveanincreasedinfluenceonAFoccurrenceifpatientshadahistoryofAF(RR1.07,95%CI0.85,1.36,P=0.57)原因心外科术后电解质异常，容量欠多见研究证据级别低，异质性大Zhu,Z.,etal.(2018).Candexmedetomidinereduceatrialfibrillationaftercardiacsurgery?Asystematicreviewandmeta-analysis.DrugDesDevelTher12:521-531.Xu,F.,etal.(2018).Theassociationbetweenintraoperativedexmedetomidineand1yearmorbidityandmortalityaftercardiacsurgery:Apropensitymatchedanalysisofover1400patients.JClinAnesth50:70-75.肾脏保护作用心肾综合征，肾前性及肾性肾功能不全多发Asignificantlyreducedincidenceofcardiacsurgery-associatedacutekidneyinjury(CSA-AKI)RCTs(relativerisk[RR]