液体复苏-胶体的地位-管向东

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1、液体复苏-胶体的地位中山大学 附属第一医院 重症医学科管向东-170多年前（1832年），一位苏格兰医师，发现了这种通过静脉静脉血管把药液送入人体的治疗手段明胶明胶GELATINGELATIN白蛋白白蛋白ALBUMINALBUMIN1915World War I1945World War II1960War In Vietnam 右旋糖苷右旋糖苷DEXTRANDEXTRAN羟乙基淀粉羟乙基淀粉1943World War II为什么要开发出这些胶体为什么要开发出这些胶体?重症液体复苏的重要性胶体及其作用目前的争论总结什么是胶体?胶体（colloid）又称胶状分散体（colloidal dispe

2、rsion）是一种均匀混合物，在胶体中含有两种不同相态的物质，一种分散，另一种连续。分散的一部分是由微小的粒子或液滴所组成，大小介于1到100纳米之间，且几乎遍布在整个连续相态中。按分散剂的不同可分为：气溶胶(雾、烟、云)；固溶胶(水晶、有色玻璃)液溶胶（蛋白溶液，淀粉溶液，肥皂水，人体血液）人体白蛋白的含量与分布人体白蛋白的含量与分布细胞内液细胞外液体液-约占人体体重60%40%组织间液15%血浆5%蛋白质在血浆中含量远远高于组织间液血浆总蛋白含量约为60-80g/L其中，白蛋白含量约为35-50g/L（占血浆总蛋白的60%)2023/7/1Frank-Starling 定律定律(Multi

3、-)OrganFailureCelldystructionCelldystructionbyimbalancebetweenbyimbalancebetweenOO22-supplyand-supplyandOO2 2-consumption-consumptionOO2 2undersupportundersupportOO2 2debtdebtMacrocirculatoryMacrocirculatorydysfunctiondysfunctionCOMicrocirculatoryMicrocirculatorydysfunctiondysfunctionWhat else besid

4、es volume restriction and expansion?Fluid resuscitationTissue oxygenationCapillary leak ameliorationHemodynamicsClinical outocmeRisk of AnaphylaxisEffect on coagulationEffect on Renal functionJean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337Acutelyillpatientsfrequentlyrequirefluidrepl

5、etionHypovolemia:external loss&internal lossRelative Hypovolemia:increases venous capacitanceVolumerepletionmaybeessential Restore critical levels of Restore critical levels of cardiac outputcardiac output and and arterial pressurearterial pressure More normal More normal perfusionperfusion of vital

6、 organs and tissues of vital organs and tissuesJean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337重症液体复苏的重要性胶体及其作用目前的争论总结复苏液体种类复苏液体种类白蛋白白蛋白血浆血浆?明胶明胶胶体液胶体液晶体液晶体液林格氏液林格氏液生理盐水生理盐水 右旋糖苷右旋糖苷羟乙基淀粉羟乙基淀粉改良明胶改良明胶HES200/0.5HES130/0.4尿联明胶尿联明胶聚明胶肽聚明胶肽天然胶体天然胶体人工胶体人工胶体高渗盐高渗盐液液7.5%盐水盐水+低右低右晶体液复苏？z赞成使用

7、晶体液的理由：z费用低，容易得到z对肾功能保持较好z很少产生不良反应。这几种液体都能纠正脱水z可纠正低钠血症z高渗盐水（HS）扩容效率高z反对使用晶体液的理由：z平均留驻时间短（只有45min）z液体输入量大z造成血清白蛋白的稀释，血渗透压降低，间质水肿、肺水肿z稀释血中凝血因子z降低血小板计数和血红细胞压积z血液携氧能力下降，降低组织氧合KoustovaE,StantonK,GushchinV,etal.Trauma2002;52:872-878.RotsteinOD.Trauma2000;49:580-83.LangK,BoldtJ,SuttnerS,etal.Analg.2001.93:

8、405-409.The edema problem of crystalloids The edema problem of crystalloids is well knownis well knownu“Fluid is poured into the Fluid is poured into the interstitial space on clinical interstitial space on clinical information gained from changes information gained from changes in intravascular spa

9、cein intravascular space.uThe The endend pointpoint,.peripheral.peripheral or or pulmonary edemapulmonary edema”Twigley&Hillman,Twigley&Hillman,Anesthesia Anesthesia 1985;40:860-871 1985;40:860-871因生存率下降NHLBI 终止高张盐水治疗休克的研究NIH所属的国立心肺血液研究所(NHLBI)已经终止了一项有关严重出血导致休克的创伤患者的临床液体复苏干预试验该试验旨在研究高张盐水溶液治疗此类患者疗效及安

10、全性试验终止的原因：观察到高张盐水治疗组患者在到达医院或急诊科前病死率显著升高，尽管高张盐水组及生理盐水组患者28天病死率（研究终点）相似 NHLBIHaltsStudyofConcentratedSalineforShockDuetoLackofSurvivalBenefit.AmericanAcademyofEmergencyMedicine2009-16(3),MedScape Today COP balance essential for balanced flow across COP balance essential for balanced flow across capill

11、arycapillary 胶体渗透压的平衡是毛细血管的交换的基本因素胶体渗透压的平衡是毛细血管的交换的基本因素胶体渗透压的平衡是毛细血管的交换的基本因素胶体渗透压的平衡是毛细血管的交换的基本因素 Crystalloids cannot Crystalloids cannot impactimpact COP Edema COP Edema 单独使用晶体无法维持胶体渗透压单独使用晶体无法维持胶体渗透压单独使用晶体无法维持胶体渗透压单独使用晶体无法维持胶体渗透压水肿水肿水肿水肿Colloids help to restore COP and reduce Crystalloid load胶体液有助

12、于恢复胶体渗透压和减少晶体负荷胶体液有助于恢复胶体渗透压和减少晶体负荷Artery(Arteriole)动脉,小动脉Vein(Venule)静脉,小静脉PlasmaProteinColloidOsmoticPressure胶体渗透压22mmHg简化简化Starling定律定律HydrostaticPressure静水压32mmHgHydrostaticPressure静水压12mmHgTissueFluid组织液Hypovolemia Edema,organ damage低低血容量血容量 水肿水肿,器官损伤器官损伤胶体渗透压胶体液的作用容量作用：容量作用：维持血流动力学稳定维持血流动力学稳定维

13、持血浆胶体渗透压维持血浆胶体渗透压改善微循环改善组织细胞氧供改善微循环改善组织细胞氧供 非容量作用：非容量作用：改善改善CLSCLS改善炎性反应改善炎性反应物质结合和转运物质结合和转运抗氧化作用抗氧化作用(colloid)151 consecutivelymajor trauma patients William C.ShoemakerOutcome Prediction of Emergency Patients by Noninvasive Hemodynamic Monitoring Chest.2001;120:528-537 William C.ShoemakerOutcome Pr

14、ediction of Emergency Patients by Noninvasive Hemodynamic Monitoring Chest.2001;120:528-537 Hemodynamcs（crystalloid）:151 consecutivelymajor trauma patientsNormalSubstance P-1 min laterStudyofCapillaryLeakDirect:Scanning EM:normal endothelial cell junction Direct:Scanning EM:normal endothelial cell j

15、unction Donald McDonald 1999Donald McDonald 1999Crit Care Med 2006;34:17751782白蛋白增加血浆中抗氧化剂含量Gregory J.etc.Crit Care Med.2004;32:755-759 The SAFE Study Alb:saline deaths 726:729(RR 0.99)Similar new organ failuresICU LOSHospital LOSVentilator durationRRTConclusion:Outcome with albumin in ICU no differ

16、ent from SalineQ:Does this mean crystalloids and colloids are the same?Does this mean all colloids are same?Finfer et al,NEJM 2004;350:2247-56重症液体复苏的重要性胶体及其作用目前的讨论总结胶体液复苏并无优势-荟萃分析Objective:the effect on mortality of resuscitation with colloid compared with crystalloids.Design:Systematic review of ra

17、ndomised controlled trials of resuscitation with colloids compared with crystalloids for critically ill patients;Subjects:37 randomised controlled trials were eligible:26 uncompounded trials that compared colloids with crystalloids(n=1622),10 trials that compared colloid in hypertonic crystalloid wi

18、th isotonic crystalloid(n=1422)and one trial that compared colloid in isotonic crystalloid with hypertonic crystalloid(n=38).SchierhoutG,RobertsI.Fluidresuscitationwithcolloidorcrystalloidsolutionsincriticallyillpatients:asystematicreviewofrandomisedtrials.BMJ 1998;316:9614.Conclusions:This systemat

19、ic review does not support the continued use of colloids for volume replacement in critically ill patients.Cochrane Report（2008）ObjectivesToassesstheeffectsofcolloidscomparedtocrystalloidsforfluidresuscitationincriticallyillpatients.Main results:identified63eligibletrials,55ofthesepresentedmortality

20、data.Colloids compared to crystalloidsAlbumin-23trialsreporteddataonmortality,includingatotalof7,754patients.Thepooledrelativerisk(RR)was1.01(95%confidenceinterval95%CI0.92to1.10).Whenthetrialwithpoorqualityallocationconcealmentwasexcluded,pooledRRwas1.00(95%CI0.91to1.09).Hydroxyethyl starch-16trial

21、scomparedhydroxyethylstarchwithcrystalloids,n=637patients.ThepooledRRwas1.05(95%CI0.63to1.75).Modified gelatin-11trialscomparedmodifiedgelatinwithcrystalloid,n=506patients.ThepooledRRwas0.91(95%CI0.49to1.72).Dextran-ninetrialscompareddextranwithacrystalloid,n=834patients.ThepooledRRwas1.24(95%CI0.94

22、to1.65).Eight trials compared dextran in hypertonic crystalloid with isotonic crystalloid,including 1,283 randomised participants.PooledRRwas0.88(95%CI0.74to1.05).PerelP,RobertsI,Colloidsversuscrystalloidsforfluidresuscitationincriticallyillpatients(Review).TheCochraneLibrary2008,Issue3Authors concl

23、usions：There is no evidence from RCTs that resuscitation with colloids reduces the risk of death,compared to resuscitation with crystalloids,in patients with trauma,burns or following surgery.胶体，ICU用，还是不用？Fluid Challengep500-100mlcristalloidsp300-500mlcolloidspover30minpcontrolCVPorPAOPandreducespee

24、d/volumeaccordingly Grade1DSurvivingSepsisCampaign:Internationalguidelinesformanagementofseveresepsisandsepticshock:2008CritCareMed2008Vol.36,No.1Figure.Differences(in percentage from baseline)of tissue oxygentension(ptio2)in the two volume groupsKatrin Lang,Joachim Boldt,Stefan Suttner,et al.Colloi

25、ds VersusCrystalloids and Tissue Oxygen Tension in Patients Undergoing Major Abdominal Surgery.Anesth Analg 2001;93:4059白蛋白对于重症患者结论：白蛋白可以显著结论：白蛋白可以显著结论：白蛋白可以显著结论：白蛋白可以显著降低重症病例降低重症病例降低重症病例降低重症病例整体并发症的发生（危险比整体并发症的发生（危险比整体并发症的发生（危险比整体并发症的发生（危险比:0.92;:0.92;可信区可信区可信区可信区间间间间:0.86-0.98):0.86-0.98)；且并发症的发生率

26、与白蛋白的使用剂量显著相关（；且并发症的发生率与白蛋白的使用剂量显著相关（；且并发症的发生率与白蛋白的使用剂量显著相关（；且并发症的发生率与白蛋白的使用剂量显著相关（p=0.002)p=0.002)(Albumin-B-004)Vincent,Jean-Louis,Navickis,Roberta J.Wilkes,Mahlon M.Morbidity in hospitalized patients receiving human albumin:A meta-analysis of randomized,controlled trials*CritCareMed2004;32(10):20

27、29-2038胶体：我们关心的组织氧代谢？SHOCK,2006 Vol.25,No.2,pp.103Y116 Schortgen et coll Lancet 2001,357,911SurvivorsHEA or gelatine for Severe Sepsis?Resuscitation:selection of FluidSAFE study:albumin vs crystalloid solutionMortality rate was identical Hypoalbuminemia is associated with higher morbidityVincent JL

28、et al,Ann Surg 2003;237:319334:meta-analysisAlbumin administration may reduce complications in critically ill patientsSAFE trial:Improved survival with albumin in patients with sepsis who are hypoalbuminemia(relative risk of death,0.87;95%CI,0.74 1.02;p 0.06)Albumin may be beneficial in this subset

29、of critically ill patientsJean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337Resuscitation:selection of FluidSynthetic colloid solution:Hydroxyethyl starch solutions:Less expensive,adverse effects on blood clottingGelatins:Smaller MW,less effective plasma expanders,low costJean-Louis Vi

30、ncent,Max Harry Weil,Crit Care Med 2006;34:13331337Resuscitation:selection of FluidNo intravenous fluid solution that is ideal in all clinical settingsNo secure data support a preference for one over anotherThe choice is best made contingent on:the underlying diseasethe type of fluid that has been l

31、ostthe severity of circulatory failurethe serum albumin concentration of the patientthe risk of bleeding.Jean-Louis Vincent,Max Harry Weil,Crit Care Med 2006;34:13331337重症液体复苏的重要性胶体及其作用目前的争论总结总 结重症病人的液体复苏，是最重要/最早的复苏手段之一容量替代、血流动力学稳定、组织氧合均是临床液体复苏的重要目标液体选择种类很多，无论何种液体（晶胶体），从使用开始，需要考虑不良作用胶体液的使用，要同时考虑容量以外问题目前，晶体或胶体复苏孰优孰劣，需要更有说服力的循证医学证据支持谢谢！