右美托咪啶的基础与临床课件

右美托咪啶的基础与临床天津医科大学总医院王国林2013-6右美托咪啶的基础与临床天津医科大学总医院1内容一般介绍作用机制、药代学、用药方法文献借鉴我们的研究内容一般介绍一、一般介绍、作用机制一、一般介绍、作用机制3背景临床工作中镇静非常重要，但近年新药很少一些常用药物特点Opiate/benzodiazepine–tolerance,efficacyPentobarbital–agitation,durationPropofol–limitedaccessinsomejurisdictionsKetamine–emergencereactions,tolerance2-adrenoreceptoragonism背景临床工作中镇静非常重要，但近年新药很少背景（2

受体激动剂）PrototypeagentisclonidineMorerecentapplicationsinclinicalpracticeSedationBehaviordisordersDrugwithdrawalHypertensionProblem–hypotensionSolution–2ndgeneration-

2specificity背景（2受体激动剂）Prototypeagentis右美托嘧啶PharmacologicallyactiveD-isomerofmedetomidine1stsynthesizedinlate1980’s,Phase1studiesinearly1990’s,clinicaltrialslate1990’s~8-foldgreater2:1selectivitythanclonidine1620:1vs200:1清除半衰期较可乐定短：2-3vs8-12hrFDAapprovedforICUsedationinadults右美托嘧啶Pharmacologicallyactive中枢作用机制Locusceruleus（蓝斑）:Brainstemcenter-modulateswakefulnessMajorsiteforhypnoticactions(sedation,anxiolysis)Mediatedviavariousefferentpathways:ThalamusandsubthalamuscortexNociceptivetransmissionviadescendingspinaltractsVasomotorcenterandreticularformationSpinalcord:

Bindingto2receptors

analgesiaviareleaseofsubstanceP中枢作用机制Locusceruleus（蓝斑）:

中枢作用机制DexmedetomidineSedation–central,G-proteins(inhibition)

Analgesia–spinalcord,SubstanceP中枢作用机制DexmedetomidineSedatio机制–CENTRAL2Presynapticreceptors:Location:SympatheticnerveendingsNoradrenergicCNSneuronsMechanism/action:TransmembranereceptorsCoupledtoGo-andGi-typeG-proteinsadenylatecyclaseandcAMPformationHyperpolarization(K+-channels)Ca++conductanceNErelease机制–CENTRAL2PresynapticrecCELLULARMECHANISMCa++Ca++Ca++––+Decreasein

influxofCa++Decreaseinaction

potentialdueto

hyperpolarizationa2Aa2ARGoGkK+K+K+CELLULARMECHANISMCa++Ca++Ca++中枢外效应高血压:peripheral1-agonism心动过缓/低血压:交感抑制-medullaryVMC寒战:Diuresis:renin,vasopressin;ANP

中枢外效应高血压:右美托咪啶的基础与临床课件呼吸系统影响Promotedashavingminimalrespiratorydepressingeffects0.17%incidenceonmonogramMostdatasuggestsSaO2andPaCO2unaffectedNumerousreportsduringspontaneousventilation呼吸系统影响Promotedashavingminim二、药代动力学二、药代动力学药代参数起效时间

镇静10min,镇痛20min达峰时间60~90min作用时间

2.5~4h生物利用度

肌注：73%蛋白结合

94%代谢 肝酶P450葡萄糖醛酸排泄 尿：95%、大便：4%分布半衰期

5min消除半衰期

2~5h药代参数起效时间 镇静10min,镇痛20min国外研究资料显示：在健康志愿者的研究中，当静脉输注剂量范围为0.2-0.7g/kg·h时，呼吸率和氧饱和度保持在正常范围内，未见呼吸抑制。静脉输注后：快速分布相的分布半衰期(t1/2)大约为6分钟；终末清除半衰期(t1/2)大约为2小时；稳态分布容积(Vss)大约为118升。清除率大约为39L/h。药代参数国外研究资料显示：在健康志愿者的研究中，当静脉输注剂量范围为静脉输注本品0.2-0.7

g

/kg﹒h直到24小时右美托咪定呈现线性动力学参数负荷输注(min)/总输注时间(hrs)10min/12hrs10min/24hrs10min/24hrs35min/24hrs右美托咪定的目标浓度(ng/mL)和剂量(g/kg/hr)0.3/0.170.3/0.170.6/0.331.25/0.70t1/2

,h1.780.302.220.592.230.212.500.61CL,L/h46.38.343.16.535.36.836.57.5Vss,L88.722.9102.420.393.617.099.617.8AvgCss,ng/mL0.270.050.270.050.670.101.370.20静脉输注本品0.2-0.7g/kg﹒h直到24小时右美老年患者：右美托咪定的药代动力学特性不随年龄而改变。年轻(18-40岁)、中年(41-65岁)和老年(65岁)受试者中右美托咪定的药代动力学无差异。儿科患者：右美托咪定在儿科患者的药代动力学特性未见详细数据，但在欧美已广泛使用。肾功能损伤：严重肾功能损伤受试者(肌酐清除率：30mL/min)右美托咪定的药代动力学(Cmax、Tmax、AUC、t1/2、CL和Vss)与健康受试者相比无明显差异特殊患者应用老年患者：特殊患者应用肝功能损伤在不同程度肝功能损伤受试者(Child-Pugh分类A、B或C)，右美托咪定的清除率值比健康受试者低，肝功能损伤患者或许需要考虑减少给药剂量肝功能损伤Child-Pugh分类ABC平均清除率（正常人的%）74%64%53%肝功能损伤在不同程度肝功能损伤受试者(Child-Pugh分药物用法负荷量1μg/kgiv10min继而0.2-0.7μg/kg/hr使用输注泵,不要推注！滴定药效肝肾功能不全、老年人适当减量药物用法负荷量1μg/kgiv10minDex围术期给药方案Example:70kgpatient.AssessBP,HR,volumestatus2mLDexin48mL0.9%saline=200ug/50mL,or4ug/mlHypovolemicStartat40mL/hrStoploadifHRUsualload:25to35ugor6to9mLover10-15minMonitorBP/HRthroughoutIfbradycardia,

infusionMaintenance:0.2to0.7ug/kg/hr[4to12mL/hr]Volumepreload

500to1000ccLRNormovolemicDex=dexmedetomidine.Dex围术期给药方案Example:70kgpati三、相关文献三、相关文献22“自然睡眠”BISKasuyaYetal.Thecorrelationbetweenbispectralindexandobservationalsedationscaleinvolunteerssedatedwithdexmedetomidineandpropofol.AnesthAnalg2009;109:1811–1815.“自然睡眠”KasuyaYetal.ThecorreDEX对ICU镇静死亡率影响PandharipandePP,etal.Effectofsedationwithdexmedetomidinevslorazepamonacutebraindysfunctioninmechanicallyventilatedpatients:theMENDSrandomizedcontrolledtrial.JAMA2007;298:2644–2653.DEX对ICU镇静死亡率影响PandharipandePP脓毒症患者的预后（SepsisvsnoSepsis）脓毒症患者的预后（SepsisvsnoSepsis）DEX与术后谵妄、POCDDEX镇静机制不同，类似“自然”睡眠的镇静是否与术后谵妄、POCD有关ICU镇静后谵妄发生率比较DEX与术后谵妄、POCDDEX镇静机制不同，类似“自然”睡PandharipandePP,etal.Effectofsedationwithdexmedetomidinevslorazepamonacutebraindysfunctioninmechanicallyventilatedpatients:theMENDSrandomizedcontrolledtrial.JAMA2007;298:2644–2653.PandharipandePP,etal.EffecRikerRR,etal.Dexmedetomidinevsmidazolamforsedationofcriticallyillpatients:arandomizedtrial.

JAMA2009;301:489–499右美或咪啶安定对ICU镇静患谵妄的比较RikerRR,etal.DexmedetomidinANESTHESIOLOGY.2009NOV;111(5):1075-84.

306例患者随机分成右美0.1-0.7µg/（kg-1•h-1)或吗啡10-70µg/（kg-1•h-1)

观察指标：谵妄Dexmedetomidinereducedthedurationbutnottheincidenceofdeliriumaftercardiacsurgerywitheffectiveanalgesia/sedation,lesshypotension,lessvasopressorrequirement,andmorebradycardiaversusmorphineregimen.心脏手术后给右美或吗啡镇痛对老年患者谵妄的影响ANESTHESIOLOGY.2009NOV;111(5

AIRWAYCATASTROPHES

CURROPINANAESTHESIOL.2009,6

Modernanestheticmedicationssuchasdexmedetomidineandproventechniquessuchasawakefiberopticintubationcanbeusedtosafelytreatthesedifficultpatients.

AIRWAYCATASTROPHES

CURROPMINERVAANESTESIOL.2009;75(11):668-71.

Thisarticledescribesthecaseofapatientwithseverechronicobstructivepulmonarydiseaseandseverecarotidstenosis,whounderwentcarotidstentingundermonitoredanesthesiacarewithdexmedetomidine.Onlyoneepisodeofbradycardiaandhypotensionwasobserved,andthiswassuccessfullytreatedwithglycopyrrolate.右美托咪啶用于合并严重慢阻肺行颈动脉支架术患者的镇静MINERVAANESTESIOL.2009;75(11.

INTJOBSTETANESTH.2009;18(4):403-7.

A35-year-old,41-kgparturientat35weeksof

gestationwithspinalmuscularatrophypresentedforcesareansection.Dexmedetomidinewasadministeredintravenously,totaldose1.84μg/kgover38minutes,followedbyfiberopticendotrachealintubation.Dexmedetomidinewasthendiscontinuedandgeneralanesthesiawasinduced.Thebabywasdelivered68minutesafterthedexmedetomidineinfusion

Duringadministrationofdexmedetomidine,maternalheartrate,bloodpressureandoxygensaturationremainedstable.Apgarscoresat1and5minwere6and8.右美用于合并脊髓性肌萎缩Ⅲ型患者剖宫产清醒气管插管.

INTJOBSTETANESTH.2009;18ANESTHANALG.2009SEP;109(3):745-53.

DexmedetomidineprovidedanacceptablelevelofanesthesiaforMRIsleepstudiesinchildrenwithOSA,producingahighyieldofinterpretablestudiesofthepatient'snativeairway.

TheneedforartificialairwaysupportduringtheMRIsleepstudywassignificantlylesswithdexmedetomidinethanwithpropofol.DexmedetomidinemaybethepreferreddrugforanesthesiaduringMRIsleepstudiesinchildrenwithahistoryofsevereOSAandmayofferbenefitstochildrenwithsleep-disorderedbreathingrequiringanesthesiaoranesthesiaforotherdiagnosticimagingstudies.右美VS丙泊酚用于小儿对MRI对睡眠的研究ANESTHANALG.2009SEP;109(3):Inadditionitpossessympatholyticandantinociceptiveeffectsthatallowhemodynamicstabilityduringsurgicalstimulation.Differentfrommostofclinicallyusedanesthetics,dexmedetomidinebringsaboutnotonlyasedative-hypnoticeffectviaanactiononasingletypeofreceptors,butalsoananalgesiceffectandanautonomicblockadethatisbeneficialincardiacrisksituations.Severalstudieshavedemonstrateditssafety,althoughbradycardiaandhypotensionarethemostpredictableandfrequentsideeffects.CURRDRUGTARGETS.2009AUG;10(8):687-95全麻中右美的应用CURRDRUGTARGETS.2009AUG;10ANESTHESIOLOGY.2009;111(5):1111-9.

Thisisthefirststudyshowingthatdexmedetomidineaddedtoropivacaineincreasesthedurationofsensoryblockadeinadose-dependentfashioninrats.Thefindingsareanessentialfirststepencouragingfutureefficacystudiesinhumans.右美加入罗哌卡因剂量依赖性延长对大鼠坐骨神经阻滞作用时间ANESTHESIOLOGY.2009;111(5):1延长局部麻醉药对外周神经阻滞的时间抑制外周神经兴奋性传导BrummettC,etal.Perineuraldexmedetomidineaddedtoropivacainecausesadose-dependentincreaseinthedurationofthermalantinociceptioninsciaticnerveblockinrat.Anesthesiology2009;111:1111–1119.延长局部麻醉药对外周神经阻滞的时间BrummettC,eAbdllahFW,etal:A&A,2013AbdllahFW,etal:A&A,2013BlaudszunG,etal:Anesthesiology,2012,112:1316与吗啡剂量进行换算BlaudszunG,etal:AnesthesioloACTAANAESTHESIOLSCAND.2009,26

Thecombinationofdexmedetomidineandhypothermiaimprovedshort-termneurologicoutcomecomparedwiththecontrolgroupwhereasthecombinationtherapyprovidedcomparableneuroprotectionwitheitherofthetwotherapiesalone.右美加低温在大鼠脑缺血再灌损伤的保护作用ACTAANAESTHESIOLSCAND.2009MASUI.2009;58(8):987-9.A64-year-oldwomanwithhypertension,diabetesmellitusandasymptomaticfirstdegreeAVblockunderwentlowanteriorresectionoftherectum.Anesthesiawasinducedwithpropofol,vecuroniumbromideandremifentanilandmaintainedwithnitrousoxideinoxygen,propofolandremifentanil.Aftertheoperation,thepatientwasadmittedtotheintensivecareunitundergeneralanesthesiawithpropofolandremifentanil.Inaddition,dexmedetomidinewasgivenwithoutloadingdose.TheEKGchangedfromfirstdegreeAVblocktoseconddegreeAVblockfollowedbycompleteAVblockandfinallycardiacarrest.Assoonasweperformedheartmassage,sinusrhythmappeared.WeshouldbecarefulingivingdexmedetomidinetoapatientwithAVblock.心跳骤停一例报告（发生于ICU）MASUI.2009;58(8):987-9.A64-y四、我们的研究四、我们的研究41

分组：A.假手术组B.假手术+右美托咪啶10μg组C.脓毒症组D.脓毒症+右美托咪啶2.5μg组E.脓毒症+右美托咪啶5μg组F.脓毒症+右美托咪啶10μg组观察指标：不同时间点动物的生存率、心率、动脉血压、动脉血pH（pHa）、动脉血氧分压（PaO2）、动脉血二氧化碳分压（PaCO2）、乳酸及心肺肝肾等组织病理变化，及动物血清IL-6、IL-10、SOD及MDA水平。右美托咪啶对脓毒症大鼠的保护效应及其机制探讨

分组：观察指标：右美托咪啶对脓毒症大鼠的保护效应及其机制探右美托咪啶的基础与临床课件心肺肝肾病理——心、肺ShamSham+Dex10CLPCLP+Dex2.5CLP+Dex5CLP+Dex10心肺肝肾病理——心、肺ShamSham+Dex10CLPCL心肺肝肾病理——肝、肾ShamSham+Dex10CLPCLP+Dex2.5CLP+Dex5CLP+Dex10心肺肝肾病理——肝、肾ShamSham+Dex10CLPCL细胞因子、抗氧化因子改变细胞因子、抗氧化因子改变46右美托咪啶右美托咪啶可以改善脓毒症大鼠的心率、血压、血气、乳酸及组织病理指标，提高生存率。这一作用是通过降低血清IL-6水平，增加血清SOD水平，降低血清MDA水平，从而减少组织损伤而实现的。结论右美托咪啶右美托咪啶可以改善脓毒症大鼠的心率、血压、血气、乳右美托咪啶节约全麻及阿片类镇痛药77例患者，45～65岁，全麻腹部手术麻醉诱导：咪唑安定0.05-0.1mg/kg，苏芬太尼0.3-0.5µg/kg，依托咪酯0.2-0.3mg/kg，顺卡0.15mg/kg右美：诱导时开始给0.5µg/kg前半小时，然后维持0.4µg/kg/hr，缝皮是停止麻醉维持丙泊酚、苏芬太尼，顺卡，BIS40~60右美托咪啶节约全麻及阿片类镇痛药77例患者，45～65岁，全顺卡用量、肌松恢复时间顺卡用量、肌松恢复时间苏芬太尼用量、苏芬太尼用量、右旋美托咪定复合丙泊酚用于胃镜检查术的临床观察

（我们的研究）60例患者随机分成右旋美托咪定复合丙泊酚与丙泊酚组泵注右旋美托咪定0.6μg/kg/hr10min，静注丙泊酚直至睫毛反射消失,呼之不应后停止泵注右美并置入内镜检查单纯注射丙泊酚视患者术中体动，呛咳情况追加丙泊酚右旋美托咪定复合丙泊酚用于胃镜检查术的临床观察

（我们的研所有病例均能顺利完成操作开始检查时BIS值下降幅度大于P组(43.6vs49.7)MAP、HR、SpO2下降幅度小于P组两组手术时间及苏醒时间无差异丙泊酚总量、不良反应发生率均少于P组（75.1vs132.3）右旋美托咪定复合丙泊酚用于胃镜检查术的临床观察

(我们的研究）所有病例均能顺利完成操作右旋美托咪定复合丙泊酚用于胃镜检查术不同剂量右美托咪啶对下腹部手术患者七氟醚MACBAR影响研究右美对七氟醚抑制50%下腹部手术切皮诱发应急反应的MAC60例患者，置入喉罩，分别给0.4μg·kg-1·h-1至1.2μg·kg-1·h-1结果：随右美剂量增加，可减少七氟醚MAC,但从0.8μg·kg-1·h-1增加到1.2μg·kg-1·h-1时，MAC不再降低，提示有封顶效应·付志强等，中华麻醉学杂志，2011，31:677~679不同剂量右美托咪啶对下腹部手术患者七氟醚MACBAR影响研究小结Goalistoestablish+maintainadequatedrugconcateffectsitetoproducedesiredeffectDexcanhelpoptimizeanesthesiavia:Sedation,analgesia+sympatheticactivityAttenuationofstressresponse+HRSmoothemergence+trachealextubationUniquemechanismofactiononnaturalsleeppathwaypermitssedation+analgesiaw/orespiratorydepressionAdjunctagentofchoiceformanysurgeries小结Goalistoestablish+maint谢谢！谢谢！右美托咪啶的基础与临床天津医科大学总医院王国林2013-6右美托咪啶的基础与临床天津医科大学总医院56内容一般介绍作用机制、药代学、用药方法文献借鉴我们的研究内容一般介绍一、一般介绍、作用机制一、一般介绍、作用机制58背景临床工作中镇静非常重要，但近年新药很少一些常用药物特点Opiate/benzodiazepine–tolerance,efficacyPentobarbital–agitation,durationPropofol–limitedaccessinsomejurisdictionsKetamine–emergencereactions,tolerance2-adrenoreceptoragonism背景临床工作中镇静非常重要，但近年新药很少背景（2

受体激动剂）PrototypeagentisclonidineMorerecentapplicationsinclinicalpracticeSedationBehaviordisordersDrugwithdrawalHypertensionProblem–hypotensionSolution–2ndgeneration-

2specificity背景（2受体激动剂）Prototypeagentis右美托嘧啶PharmacologicallyactiveD-isomerofmedetomidine1stsynthesizedinlate1980’s,Phase1studiesinearly1990’s,clinicaltrialslate1990’s~8-foldgreater2:1selectivitythanclonidine1620:1vs200:1清除半衰期较可乐定短：2-3vs8-12hrFDAapprovedforICUsedationinadults右美托嘧啶Pharmacologicallyactive中枢作用机制Locusceruleus（蓝斑）:Brainstemcenter-modulateswakefulnessMajorsiteforhypnoticactions(sedation,anxiolysis)Mediatedviavariousefferentpathways:ThalamusandsubthalamuscortexNociceptivetransmissionviadescendingspinaltractsVasomotorcenterandreticularformationSpinalcord:

Bindingto2receptors

analgesiaviareleaseofsubstanceP中枢作用机制Locusceruleus（蓝斑）:

中枢作用机制DexmedetomidineSedation–central,G-proteins(inhibition)

Analgesia–spinalcord,SubstanceP中枢作用机制DexmedetomidineSedatio机制–CENTRAL2Presynapticreceptors:Location:SympatheticnerveendingsNoradrenergicCNSneuronsMechanism/action:TransmembranereceptorsCoupledtoGo-andGi-typeG-proteinsadenylatecyclaseandcAMPformationHyperpolarization(K+-channels)Ca++conductanceNErelease机制–CENTRAL2PresynapticrecCELLULARMECHANISMCa++Ca++Ca++––+Decreasein

influxofCa++Decreaseinaction

potentialdueto

hyperpolarizationa2Aa2ARGoGkK+K+K+CELLULARMECHANISMCa++Ca++Ca++中枢外效应高血压:peripheral1-agonism心动过缓/低血压:交感抑制-medullaryVMC寒战:Diuresis:renin,vasopressin;ANP

中枢外效应高血压:右美托咪啶的基础与临床课件呼吸系统影响Promotedashavingminimalrespiratorydepressingeffects0.17%incidenceonmonogramMostdatasuggestsSaO2andPaCO2unaffectedNumerousreportsduringspontaneousventilation呼吸系统影响Promotedashavingminim二、药代动力学二、药代动力学药代参数起效时间

镇静10min,镇痛20min达峰时间60~90min作用时间

2.5~4h生物利用度

肌注：73%蛋白结合

94%代谢 肝酶P450葡萄糖醛酸排泄 尿：95%、大便：4%分布半衰期

5min消除半衰期

2~5h药代参数起效时间 镇静10min,镇痛20min国外研究资料显示：在健康志愿者的研究中，当静脉输注剂量范围为0.2-0.7g/kg·h时，呼吸率和氧饱和度保持在正常范围内，未见呼吸抑制。静脉输注后：快速分布相的分布半衰期(t1/2)大约为6分钟；终末清除半衰期(t1/2)大约为2小时；稳态分布容积(Vss)大约为118升。清除率大约为39L/h。药代参数国外研究资料显示：在健康志愿者的研究中，当静脉输注剂量范围为静脉输注本品0.2-0.7

g

/kg﹒h直到24小时右美托咪定呈现线性动力学参数负荷输注(min)/总输注时间(hrs)10min/12hrs10min/24hrs10min/24hrs35min/24hrs右美托咪定的目标浓度(ng/mL)和剂量(g/kg/hr)0.3/0.170.3/0.170.6/0.331.25/0.70t1/2

,h1.780.302.220.592.230.212.500.61CL,L/h46.38.343.16.535.36.836.57.5Vss,L88.722.9102.420.393.617.099.617.8AvgCss,ng/mL0.270.050.270.050.670.101.370.20静脉输注本品0.2-0.7g/kg﹒h直到24小时右美老年患者：右美托咪定的药代动力学特性不随年龄而改变。年轻(18-40岁)、中年(41-65岁)和老年(65岁)受试者中右美托咪定的药代动力学无差异。儿科患者：右美托咪定在儿科患者的药代动力学特性未见详细数据，但在欧美已广泛使用。肾功能损伤：严重肾功能损伤受试者(肌酐清除率：30mL/min)右美托咪定的药代动力学(Cmax、Tmax、AUC、t1/2、CL和Vss)与健康受试者相比无明显差异特殊患者应用老年患者：特殊患者应用肝功能损伤在不同程度肝功能损伤受试者(Child-Pugh分类A、B或C)，右美托咪定的清除率值比健康受试者低，肝功能损伤患者或许需要考虑减少给药剂量肝功能损伤Child-Pugh分类ABC平均清除率（正常人的%）74%64%53%肝功能损伤在不同程度肝功能损伤受试者(Child-Pugh分药物用法负荷量1μg/kgiv10min继而0.2-0.7μg/kg/hr使用输注泵,不要推注！滴定药效肝肾功能不全、老年人适当减量药物用法负荷量1μg/kgiv10minDex围术期给药方案Example:70kgpatient.AssessBP,HR,volumestatus2mLDexin48mL0.9%saline=200ug/50mL,or4ug/mlHypovolemicStartat40mL/hrStoploadifHRUsualload:25to35ugor6to9mLover10-15minMonitorBP/HRthroughoutIfbradycardia,

infusionMaintenance:0.2to0.7ug/kg/hr[4to12mL/hr]Volumepreload

500to1000ccLRNormovolemicDex=dexmedetomidine.Dex围术期给药方案Example:70kgpati三、相关文献三、相关文献77“自然睡眠”BISKasuyaYetal.Thecorrelationbetweenbispectralindexandobservationalsedationscaleinvolunteerssedatedwithdexmedetomidineandpropofol.AnesthAnalg2009;109:1811–1815.“自然睡眠”KasuyaYetal.ThecorreDEX对ICU镇静死亡率影响PandharipandePP,etal.Effectofsedationwithdexmedetomidinevslorazepamonacutebraindysfunctioninmechanicallyventilatedpatients:theMENDSrandomizedcontrolledtrial.JAMA2007;298:2644–2653.DEX对ICU镇静死亡率影响PandharipandePP脓毒症患者的预后（SepsisvsnoSepsis）脓毒症患者的预后（SepsisvsnoSepsis）DEX与术后谵妄、POCDDEX镇静机制不同，类似“自然”睡眠的镇静是否与术后谵妄、POCD有关ICU镇静后谵妄发生率比较DEX与术后谵妄、POCDDEX镇静机制不同，类似“自然”睡PandharipandePP,etal.Effectofsedationwithdexmedetomidinevslorazepamonacutebraindysfunctioninmechanicallyventilatedpatients:theMENDSrandomizedcontrolledtrial.JAMA2007;298:2644–2653.PandharipandePP,etal.EffecRikerRR,etal.Dexmedetomidinevsmidazolamforsedationofcriticallyillpatients:arandomizedtrial.

JAMA2009;301:489–499右美或咪啶安定对ICU镇静患谵妄的比较RikerRR,etal.DexmedetomidinANESTHESIOLOGY.2009NOV;111(5):1075-84.

306例患者随机分成右美0.1-0.7µg/（kg-1•h-1)或吗啡10-70µg/（kg-1•h-1)

观察指标：谵妄Dexmedetomidinereducedthedurationbutnottheincidenceofdeliriumaftercardiacsurgerywitheffectiveanalgesia/sedation,lesshypotension,lessvasopressorrequirement,andmorebradycardiaversusmorphineregimen.心脏手术后给右美或吗啡镇痛对老年患者谵妄的影响ANESTHESIOLOGY.2009NOV;111(5

AIRWAYCATASTROPHES

CURROPINANAESTHESIOL.2009,6

Modernanestheticmedicationssuchasdexmedetomidineandproventechniquessuchasawakefiberopticintubationcanbeusedtosafelytreatthesedifficultpatients.

AIRWAYCATASTROPHES

CURROPMINERVAANESTESIOL.2009;75(11):668-71.

Thisarticledescribesthecaseofapatientwithseverechronicobstructivepulmonarydiseaseandseverecarotidstenosis,whounderwentcarotidstentingundermonitoredanesthesiacarewithdexmedetomidine.Onlyoneepisodeofbradycardiaandhypotensionwasobserved,andthiswassuccessfullytreatedwithglycopyrrolate.右美托咪啶用于合并严重慢阻肺行颈动脉支架术患者的镇静MINERVAANESTESIOL.2009;75(11.

INTJOBSTETANESTH.2009;18(4):403-7.

A35-year-old,41-kgparturientat35weeksof

gestationwithspinalmuscularatrophypresentedforcesareansection.Dexmedetomidinewasadministeredintravenously,totaldose1.84μg/kgover38minutes,followedbyfiberopticendotrachealintubation.Dexmedetomidinewasthendiscontinuedandgeneralanesthesiawasinduced.Thebabywasdelivered68minutesafterthedexmedetomidineinfusion

Duringadministrationofdexmedetomidine,maternalheartrate,bloodpressureandoxygensaturationremainedstable.Apgarscoresat1and5minwere6and8.右美用于合并脊髓性肌萎缩Ⅲ型患者剖宫产清醒气管插管.

INTJOBSTETANESTH.2009;18ANESTHANALG.2009SEP;109(3):745-53.

DexmedetomidineprovidedanacceptablelevelofanesthesiaforMRIsleepstudiesinchildrenwithOSA,producingahighyieldofinterpretablestudiesofthepatient'snativeairway.

TheneedforartificialairwaysupportduringtheMRIsleepstudywassignificantlylesswithdexmedetomidinethanwithpropofol.DexmedetomidinemaybethepreferreddrugforanesthesiaduringMRIsleepstudiesinchildrenwithahistoryofsevereOSAandmayofferbenefitstochildrenwithsleep-disorderedbreathingrequiringanesthesiaoranesthesiaforotherdiagnosticimagingstudies.右美VS丙泊酚用于小儿对MRI对睡眠的研究ANESTHANALG.2009SEP;109(3):Inadditionitpossessympatholyticandantinociceptiveeffectsthatallowhemodynamicstabilityduringsurgicalstimulation.Differentfrommostofclinicallyusedanesthetics,dexmedetomidinebringsaboutnotonlyasedative-hypnoticeffectviaanactiononasingletypeofreceptors,butalsoananalgesiceffectandanautonomicblockadethatisbeneficialincardiacrisksituations.Severalstudieshavedemonstrateditssafety,althoughbradycardiaandhypotensionarethemostpredictableandfrequentsideeffects.CURRDRUGTARGETS.2009AUG;10(8):687-95全麻中右美的应用CURRDRUGTARGETS.2009AUG;10ANESTHESIOLOGY.2009;111(5):1111-9.

Thisisthefirststudyshowingthatdexmedetomidineaddedtoropivacaineincreasesthedurationofsensoryblockadeinadose-dependentfashioninrats.Thefindingsareanessentialfirststepencouragingfutureefficacystudiesinhumans.右美加入罗哌卡因剂量依赖性延长对大鼠坐骨神经阻滞作用时间ANESTHESIOLOGY.2009;111(5):1延长局部麻醉药对外周神经阻滞的时间抑制外周神经兴奋性传导BrummettC,etal.Perineuraldexmedetomidineaddedtoropivacainecausesadose-dependentincreaseinthedurationofthermalantinociceptioninsciaticnerveblockinrat.Anesthesiology2009;111:1111–1119.延长局部麻醉药对外周神经阻滞的时间BrummettC,eAbdllahFW,etal:A&A,2013AbdllahFW,etal:A&A,2013BlaudszunG,etal:Anesthesiology,2012,112:1316与吗啡剂量进行换算BlaudszunG,etal:AnesthesioloACTAANAESTHESIOLSCAND.2009,26

Thecombinationofdexmedetomidineandhypothermiaimprovedshort-termneurologicoutcomecomparedwiththecontrolgroupwhereasthecombinationtherapyprovidedcomparableneuroprotectionwitheitherofthetwotherapiesalone.右美加低温在大鼠脑缺血再灌损伤的保护作用ACTAANAESTHESIOLSCAND.2009MASUI.2009;58(8):987-9.A64-year-oldwomanwithhypertension,diabetesmellitusandasymptomaticfirstdegreeAVblockunderwentlowanteriorresectionoftherectum.Anesthesiawasinducedwithpropofol,vecuroniumbromideandremifentanilandmaintainedwithnitrousoxideinoxygen,propofolandremifentanil.Aftertheoperation,thepatientwasadmittedtotheintensivecareunitundergeneralanesthes