微循環和血管活性藥引言Sepsis：疑問：臨床上血流動力學穩定、氧傳遞指標等均可，但依然進展、乳酸升高？早期亦已存在微循環功能障礙！！

2微循環和血管活性藥引言微循環：如此重要、關鍵應成為危重患者復蘇中的一個關鍵指標但：傳統的評價指標難以準確評價微循環！3微循環和血管活性藥主要問題：1.有什么新的方法監測微循環？2.現有血管活性藥物微循環的影響如何？4微循環和血管活性藥微循環的結構直徑<300um的血管100億個毛細血管血管表面積>500m2組成：微動脈，后微動脈，毛細血管前括約肌，真毛細血管、通血毛細血管、動靜脈交通支、微靜脈

5微循環和血管活性藥微循環的功能及分類1.迂回通路：物質交換，交替開放（又稱營養通路）2.直捷通路：不進行物質交換，血液快速回流，骨骼肌多見3.動靜脈短路：不進行物質交換，皮膚多見6微循環和血管活性藥7微循環和血管活性藥Sepsis時微循環的改變1994年，LamC等對血壓穩定的鼠sepsis微循環活體顯微鏡在體觀察，發現sepsis時：1.灌注毛細血管密度減少，血流停止的毛細血管數增加；2.灌注毛細血管空間分布不均，平均毛細血管間距增加2002年，DeBacker等利用OPS成像觀察sepsis舌下微循環，發現：1.微血管密度顯著減少，血流停滯和血流灌注間斷的小血管比例增加；2.各區域間灌注血管的變異系數明顯大于健康志愿者

DeBackerD,CreteurJ,PreiserJC,etal.Microvascularbloodflowisalteredinpatientswithsepsis.AMJRespirCritCareMed,2002,166:98-1048微循環和血管活性藥

OPS圖像9微循環和血管活性藥Sepsis時微循環的改變特征：1.adecreaseincapillarydensity2.anincreaseinheterogeneityofperfusionwithnon-perfusedinclosevicinitytowell-perfusedcapillaries后果？10微循環和血管活性藥Tissuestoleratebetterahomogeneous

decreaseinbloodflowbetterthanaheterogeneousoneDanielDeBacker，GustavoOspina-Tascon，etal.IntensiveCareMed(2010)36:1813–1825.11微循環和血管活性藥12微循環和血管活性藥HowtoevaluatethemicrocirculationIntensiveCareMed(2010)36:1813–1825.13微循環和血管活性藥NailfoldvideocapillaroscopyThefirstmethodusedatthebedsidethenailfoldareaisverysensitivetochangesintemperature:onecancontrolambientbutnotbodytemperature.PeripheralvasoconstrictioncanalsooccurduringchillsandacutecirculatoryfailureOflimiteduseincriticallyillpatients.14微循環和血管活性藥LaserDopplerMainlimitation：measuresflowinavariablevolumeoftissue，unabletodetectitinindividualvesselsSamplingvolume:0.5and1mm3,about50vesselsCannotshowtheheterogeneity15微循環和血管活性藥SvO2VenousO2saturationcanbehighorlowforthesamedegreeofmicrovascularshunting—canbemisleadingSeveralstudieshaveshownthatmeasuringSvO2doesnotprovidemuchinformationaboutmicrovascularalterations---PodbregarM,MozinaH.Skeletalmuscleoxygensaturationdoesnotestimatemixedvenousoxygensaturationinpatientswithsevereleftheartfailureandadditionalseveresepsisorsepticshock.CritCare2007,11:R6MarikPE,BankovA,Sublingualcapnometryversustraditionalmarkersoftissueoxygenationincriticallyillpatients.CritCareMed2003,31:818–82216微循環和血管活性藥GastrictonometryAgastricPCO2gapabove20mmHgdiscriminatedsurvivorsfromnon-survivors-------LevyB,GawalkiewiczP.CritCareMed2003,31:474–48

GastricPCO2gap---mostlyreflectsgutmucosalmicrocirculation----Insepsis,nocorrelationbetweenthegastricPCO2gapandtotalsplanchnicperfusionDuodeno-gastricrefluxandfeedingcaninterfere17微循環和血管活性藥LactateTimelag-------Cannotdetectalterationsinmicrovascularperfusionbeforetheyareassociatedwithcellularhypoxia18微循環和血管活性藥OPS/SDFOPS成像：正交偏振光譜成像orthogonalpolarizationspectralimaging原理：利用血細胞對偏振入射綠光產生消偏振光散射和對正偏振光的成像特征，能在皮下0.5mm深度內產生高清晰度和高分辨率的成像。局限性：敏感性偏差；需具備高能光源，難以應用到臨床。19微循環和血管活性藥OPS/SDFSDF成像：旁流暗場成像，sidestreamdark-field，2007年開始應用于臨床優點：更加清晰所需能量小，可以方便的使用電池床邊操作

20微循環和血管活性藥SDFimage21微循環和血管活性藥OPS/SDFAdvantage:1.visible2.differentvariablescanbeobservedandbemeasured---vasculardensity,heterogeneityofperfusion,microvascularbloodflowTheconsensusadvisesreportingofPVD,PPV,MFIandheterogeneityindex,inordertodescribethefunctionalperfusionofthemicrocirculation.-------Howtoevaluatethemicrocirculation:reportofaroundtableconference,CriticalCare2007,11:R101

22微循環和血管活性藥血管活性藥物對微循環的影響Vasopressors:Norepinephrine,Epinephrine,VasopressinInotropes:Dopamine,Dobutamine,Vasodilators:Nitroglycerin,Prostacyclin23微循環和血管活性藥NEdoesnotimprovemicrocirculatorybloodflow20septicshockpatientsBasalmeasurementofMAP65mmHg,NEwastitratedtoreachaMAPof75mmHg,then85mmHgSublingualmicrocirculationwasevaluatedbySDFimagingDubinA,PozoMO,etal.Increasingarterialbloodpressurewithnorepinephrinedoesnotimprovemicrocirculatorybloodflow:aprospectivestudy.Critcare,2009,13(3):R9224微循環和血管活性藥NEdoesnotimprovemicrocirculatorybloodflow26微循環和血管活性藥NEdoesnotimprovemicrocirculatorybloodflow1.NEdoesnotimprovemicrocirculataryperfusionfurtherincreaseMAPfrom65mmHg.2.ReductionsintheperfusedcapillarydensitiesfurtherincreaseMAPfrom65mmHg.結論：使用去甲升高MAP并不是改善感染性休克患者微循環的一個恰當方法，反而可能對患者有害。27微循環和血管活性藥TheeffectofincreasingdosesofNEontissueoxygenationandmicrovascularflowinpatientswithsepticshock16septicshockpatientsNEfrom0.18to0.25,0.35,0.41ug/kg.minMAPfrom60-70-80-90mmHgSDFimaging

ShamanJhanji,etal.CritcareMed2009;37:1961-196628微循環和血管活性藥TheeffectofincreasingdosesofNEontissueoxygenationandmicrovascularflowinpatientswithsepticshockMAP高于60-65mmHg不能改善感染性休克患者微循環增加NE對感染性休克患者微循環無明顯影響

ShamanJhanji,etal.CritcareMed2009;37:1961-196629微循環和血管活性藥多巴胺對微循環的影響1.1Meier-HellmannA,BredleDL,SpechtM,SpiesC,HannemannL,ReinhartK(1997)Theeffectsoflow-dosedopamineonsplanchnicbloodflowandoxygenuptakeinpatientswithsepticshock.IntensiveCareMed23:31–371.2OlsonD,PohlmanA,HallJB(1996)Administrationoflow-dosedopaminetononoliguricpatientswithsepsissyndromedoesnotraiseintramucosalgastricpHnorimprovecreatinineclearance.AmJRespirCritCareMed154:1664–16702.MarikPE,MohedinM(1994)Thecontrastingeffectsofdopamineandnorepinephrineonsystemicandsplanchnicoxygenutilizationinhyperdynamicsepsis.JAMA272:1354–135730微循環和血管活性藥NG對微循環的影響31微循環和血管活性藥NGinsepticshockafterintravascularvolumeresuscitation8septicshockpatientsMAPwasgreaterthan60mmHgandCVPgreaterthan12mmHgafterinfusionofcrystalloidsandcolloids,andthelowestpossibledoseofdopamineNG：anintravenousloadingdoseof0·5mg,thensubsequentcontinuousinfusionof2mg/hOPS：usedtoproduceimagesofsublingualmicrocirculationLancet2002;360:1395-139632微循環和血管活性藥NGinsepticshockafterintravascularvolumeresuscitation33微循環和血管活性藥OPSimages34微循環和血管活性藥70個Severesepsis和septicshock患者充分復蘇后給予硝酸甘油或安慰劑SDF評估舌下微循環主要終點：sublingualmicrocirculatorybloodflowofsmallvesselsCritCareMed2010;38:93-10035微循環和血管活性藥Microvascularvariablesovertime36微循環和血管活性藥TakeHomeMessage1.重視微循環檢測2.sepsis微循環功能障礙：異質性