液體復蘇膠體地位

液體復蘇膠體地位---170多年前（1832一位蘇格蘭醫(yī)師，發(fā)現(xiàn)了這種通過靜脈血管把藥液送入人體的治療手段……明膠GELATIN白蛋白ALBUMIN1915WorldWarI1945WorldWarII1960’WarInVietnam右旋糖苷DEXTRAN羥乙基淀粉1943WorldWarII為什么要開發(fā)出這些膠體?重癥液體復蘇的重要性膠體及其作用目前的爭論總結(jié)什么是膠體?膠體（colloid）又稱膠狀分散體（colloidaldispersion）是一種均勻混合物，在膠體中含有兩種不同相態(tài)的物質(zhì)，一種分散，另一種連續(xù)。分散的一部分是由微小的粒子或液滴所組成，大小介于1到100納米之間，且?guī)缀醣椴荚谡麄€連續(xù)相態(tài)中。按分散劑的不同可分為：氣溶膠(霧、煙、云)；固溶膠(水晶、有色玻璃)液溶膠（蛋白溶液，淀粉溶液，肥皂水，人體血液）人體白蛋白的含量與分布細胞內(nèi)液細胞外液體液-約占人體體重60%40%組織間液15%血漿5%蛋白質(zhì)在血漿中含量遠遠高于組織間液血漿總蛋白含量約為60-80g/L其中，白蛋白含量約為35-50g/L（占血漿總蛋白的60%)2023/1/12Frank-Starling定律(Multi-)OrganFailureCelldystructionbyimbalancebetweenO2-supplyandO2-consumptionO2undersupportO2debtMacrocirculatorydysfunction

COMicrocirculatorydysfunctionWhatelsebesidesvolumerestrictionandexpansion?FluidresuscitationTissueoxygenationCapillaryleakameliorationHemodynamicsClinicaloutocmeRiskofAnaphylaxisEffectoncoagulationEffectonRenalfunctionJean-LouisVincent,MaxHarryWeil,CritCareMed2006;34:1333–1337IntroductionAcutelyillpatientsfrequentlyrequirefluidrepletion.HypovolemiaExternalloss:bleeding,gastrointestinal,urinarytracts,skinInternalloss:extravasationofblood,exudation/transudationoffluidsRelativeHypovolemia:increasesvenouscapacitanceSepsis,drugsVolumerepletionmaybeessentialtorestorecriticallevelsofcardiacoutputandarterialpressure,resultinginmorenormalperfusionofvitalorgansandtissues.Jean-LouisVincent,MaxHarryWeil,CritCareMed2006;34:1333–1337AcutelyillpatientsfrequentlyrequirefluidrepletionHypovolemia:externalloss&internallossRelativeHypovolemia:increasesvenouscapacitanceVolumerepletionmaybeessentialRestorecriticallevelsofcardiacoutputandarterialpressureMorenormalperfusionofvitalorgansandtissuesJean-LouisVincent,MaxHarryWeil,CritCareMed2006;34:1333–1337IntroductionHemorrhage:Benefit/riskoffluidrepletionmustbeassessedBenefitsofdelayedresuscitationLargevolumeoffluidredcelldeficitoxygendeficitPersistenthypovolemiawillresultinMODSFluidrepletionistypicallymoreeffectiveduringhypovolemicstatesbutislesseffectiveinlaterstages.Jean-LouisVincent,MaxHarryWeil,CritCareMed2006;34:1333–1337“fluidchallenge”Jean-LouisVincent,MaxHarryWeil,CritCareMed2006;34:1333–1337DistinguishedfromconventionalfluidadministrationUsuallytocriticalpatientswithcardiorespiratoryfailureThefluidchallengeisreservedforhemodynamicallyunstablepatientsandoffersthreemajoradvantages:Quantitationofthecardiovascularresponseduringvolumeinfusion.Promptcorrectionoffluiddeficits.Minimizingtheriskoffluidoverloadanditspotentiallyadverseeffects,especiallyonthelungs.重癥液體復蘇的重要性膠體及其作用目前的爭論總結(jié)復蘇液體種類白蛋白血漿?明膠膠體液晶體液林格氏液生理鹽水

右旋糖苷羥乙基淀粉改良明膠HES200/0.5HES130/0.4尿聯(lián)明膠聚明膠肽天然膠體人工膠體高滲鹽液7.5%鹽水+低右晶體液復蘇？贊成使用晶體液的理由：費用低，容易得到對腎功能保持較好很少產(chǎn)生不良反應。這幾種液體都能糾正脫水可糾正低鈉血癥高滲鹽水（HS）擴容效率高反對使用晶體液的理由：平均留駐時間短（只有45min）液體輸入量大造成血清白蛋白的稀釋，血滲透壓降低，間質(zhì)水腫、肺水腫稀釋血中凝血因子降低血小板計數(shù)和血紅細胞壓積血液攜氧能力下降，降低組織氧合KoustovaE,StantonK,GushchinV,etal.Trauma2002;52:872-878.RotsteinOD.Trauma2000;49:580-83.LangK,BoldtJ,SuttnerS,etal.

Analg.2001.93:405-409.Theedemaproblemofcrystalloidsiswellknown“Fluidispouredintotheinterstitialspaceonclinicalinformationgainedfromchangesinintravascularspace….…Theend

point,….peripheralorpulmonaryedema”Twigley&Hillman,Anesthesia1985;40:860-871因生存率下降

NHLBI終止高張鹽水治療休克的研究NIH所屬的國立心肺血液研究所(NHLBI)已經(jīng)終止了一項有關嚴重出血導致休克的創(chuàng)傷患者的臨床液體復蘇干預試驗該試驗旨在研究高張鹽水溶液治療此類患者療效及安全性試驗終止的原因：觀察到高張鹽水治療組患者在到達醫(yī)院或急診科前病死率顯著升高，盡管高張鹽水組及生理鹽水組患者28天病死率（研究終點）相似

NHLBIHaltsStudyofConcentratedSalineforShockDuetoLackofSurvivalBenefit.AmericanAcademyofEmergencyMedicine

2009-16(3),

MedScapeToday

COPbalanceessentialforbalancedflowacrosscapillary

膠體滲透壓的平衡是毛細血管的交換的基本因素CrystalloidscannotimpactCOP→Edema

單獨使用晶體無法維持膠體滲透壓→水腫ColloidshelptorestoreCOPandreduceCrystalloidload膠體液有助于恢復膠體滲透壓和減少晶體負荷

Artery

(Arteriole)動脈,小動脈Vein

(Venule)靜脈,小靜脈PlasmaProtein

ColloidOsmoticPressure膠體滲透壓22mmHg簡化Starling定律HydrostaticPressure靜水壓32mmHgHydrostaticPressure靜水壓12mmHgTissueFluid組織液HypovolemiaEdema,organdamage低血容量水腫,器官損傷膠體滲透壓膠體液的作用容量作用：維持血流動力學穩(wěn)定維持血漿膠體滲透壓改善微循環(huán)／改善組織細胞氧供

非容量作用：改善CLS改善炎性反應物質(zhì)結(jié)合和轉(zhuǎn)運抗氧化作用……(colloid)151consecutively

majortraumapatientsWilliamC.Shoemaker

OutcomePredictionofEmergencyPatientsbyNoninvasiveHemodynamicMonitoringChest.2001;120:528-537WilliamC.Shoemaker

OutcomePredictionofEmergencyPatientsbyNoninvasiveHemodynamicMonitoringChest.2001;120:528-537Hemodynamcs（crystalloid）:151consecutively

majortraumapatientsNormalSubstanceP-1minlaterStudyofCapillaryLeakDirect:ScanningEM:normalendothelialcelljunctionDonaldMcDonald1999Crit

CareMed2006;34:1775–1782白蛋白增加血漿中抗氧化劑硫醇含量GregoryJ.etc.CritCareMed.2004;32:755-759

白蛋白增加血漿中抗氧化劑含量GregoryJ.etc.CritCareMed.2004;32:755-759

TheSAFEStudy

Alb:salinedeaths726:729(RR0.99)SimilarneworganfailuresICULOSHospitalLOSVentilatordurationRRTConclusion:OutcomewithalbumininICUnodifferentfromSalineQ:Doesthismeancrystalloidsandcolloidsarethesame?Doesthismeanallcolloidsaresame?Finferetal,NEJM2004;350:2247-56重癥液體復蘇的重要性膠體及其作用目前的討論總結(jié)膠體液復蘇并無優(yōu)勢------薈萃分析Objective:theeffectonmortalityofresuscitationwithcolloidcomparedwithcrystalloids.Design:Systematicreviewofrandomisedcontrolledtrialsofresuscitationwithcolloidscomparedwithcrystalloidsforcriticallyillpatients;Subjects:37randomisedcontrolledtrialswereeligible:

26uncompoundedtrialsthatcomparedcolloidswithcrystalloids(n=1622),

10trialsthatcomparedcolloidinhypertoniccrystalloidwithisotoniccrystalloid(n=1422)

andonetrialthatcomparedcolloidinisotoniccrystalloidwithhypertoniccrystalloid(n=38).SchierhoutG,RobertsI.Fluidresuscitationwithcolloidor

crystalloidsolutionsincriticallyillpatients:asystematic

reviewofrandomisedtrials.BMJ

1998;316:961-4.Conclusions:Thissystematicreviewdoesnotsupportthecontinueduseofcolloidsforvolumereplacementincriticallyillpatients.Cochrane

Report（2008）ObjectivesToassesstheeffectsofcolloidscomparedtocrystalloidsforfluidresuscitationincriticallyillpatients.Mainresults:identified63eligibletrials,55ofthesepresentedmortalitydata.Colloidscomparedtocrystalloids?Albumin-23trialsreporteddataonmortality,includingatotalof7,754patients.Thepooledrelative

risk(RR)was1.01(95%confidenceinterval[95%CI]0.92to1.10).Whenthetrialwithpoorqualityallocation

concealmentwasexcluded,pooledRRwas1.00(95%CI0.91to1.09).?Hydroxyethylstarch-16trialscomparedhydroxyethylstarchwithcrystalloids,n=637patients.ThepooledRRwas1.05(95%

CI0.63to1.75).?Modifiedgelatin-11trialscomparedmodifiedgelatinwithcrystalloid,n=506patients.ThepooledRRwas0.91(95%CI0.49to1.72).?Dextran-ninetrialscompareddextranwithacrystalloid,n=834patients.ThepooledRRwas1.24(95%CI0.94to1.65).?Eighttrialscompareddextraninhypertoniccrystalloidwithisotoniccrystalloid,including1,283randomisedparticipants.Pooled

RRwas0.88(95%CI0.74to1.05).PerelP,RobertsI,Colloidsversuscrystalloidsforfluidresuscitationincriticallyillpatients(Review).TheCochraneLibrary2008,Issue3Authors’conclusions：ThereisnoevidencefromRCTsthatresuscitationwithcolloidsreducestheriskofdeath,comparedtoresuscitationwithcrystalloids,

inpatientswith

trauma,burnsorfollowingsurgery.Cochrane

Report（2008）Ascolloidsarenotassociatedwithanimprovementinsurvival,andastheyare

moreexpensivethancrystalloids,itishardtoseehowtheircontinueduseinthesepatientscanbejustifiedoutsidethecontextofRCTs.PerelP,RobertsI,Colloidsversuscrystalloidsforfluidresuscitationincriticallyillpatients(Review).TheCochraneLibrary2008,Issue3注：Cochrane是國際最大的循證醫(yī)學試驗的協(xié)作網(wǎng)，以已故英國內(nèi)科醫(yī)師和著名流行病學家Archie

Cochrane的名字命名膠體，ICU用，還是不用？FluidChallenge

500-100mlcristalloids300-500mlcolloidsover30mincontrolCVPorPAOPandreducespeed/volumeaccordingly

Grade1DSurvivingSepsisCampaign:Internationalguidelinesfor

managementofseveresepsisandsepticshock:2008CritCareMed2008Vol.36,No.1Figure.Differences(inpercentagefrombaseline)oftissueoxygentension(ptio2)inthetwovolumegroupsKatrinLang,JoachimBoldt,StefanSuttner,etal.

ColloidsVersusCrystalloidsandTissueOxygenTensioninPatientsUndergoingMajorAbdominalSurgery.AnesthAnalg2001;93:405–9白蛋白對于重癥患者結(jié)論：白蛋白可以顯著降低重癥病例整體并發(fā)癥的發(fā)生（危險比:0.92;可信區(qū)間:0.86-0.98)；且并發(fā)癥的發(fā)生率與白蛋白的使用劑量顯著相關（p=0.002)(Albumin-B-004)Vincent,Jean-Louis,Navickis,RobertaJ.Wilkes,MahlonM.

Morbidityinhospitalizedpatientsreceivinghumanalbumin:Ameta-analysisofrandomized,controlledtrials*

CritCareMed2004;32(10):2029-2038膠體：我們關心的組織氧代謝？SHOCK,2006

Vol.25,No.2,pp.103Y116 SchortgenetcollLancet2001,357,911SurvivorsHEAorgelatineforSevereSepsis?Resuscitation:selectionofFluidCrystalloidsorColloidscanbeusedFluidchallengeswithcolloidsallowformorerapidcompletionofchallenge.Crystalloid:Physiologic(0.9%)saltsolution(saline)MayincreaseserumchlorideconcentrationsBalancedsaltsolutions(Ringer’slactate/Hartmann’ssolution)Mildlyhypotonic,mayexacerbatecerebraledemaJean-LouisVincent,MaxHarryWeil,CritCareMed2006;34:1333–1337Resuscitation:selectionofFluidSAFEstudy:albuminvscrystalloidsolutionMortalityratewasidenticalHypoalbuminemiaisassociatedwithhighermorbidityVincentJLetal,AnnSurg