全身性感染与感染性休克.ppt

全身性感染(sepsis):定义,确证或可疑的感染,以及某些下列指标一般指标炎症指标血流动力学指标器官功能不全指标组织灌注指标,LevyMM,FinkMP,MarshallJC,AbrahamE,AngusD,CookD,CohenJ,OpalSM,VincentJL,RamsayG,FortheInternationalSepsisDefinitionsConference.2001SCCM/ESICM/ACCP/ATS/SISInternationalSepsisDefinitionsConference.CritCareMed2003;31:1250-1256,全身性感染(sepsis):定义,LevyMM,FinkMP,MarshallJC,AbrahamE,AngusD,CookD,CohenJ,OpalSM,VincentJL,RamsayG,FortheInternationalSepsisDefinitionsConference.2001SCCM/ESICM/ACCP/ATS/SISInternationalSepsisDefinitionsConference.CritCareMed2003;31:1250-1256,全身性感染(sepsis):定义,LevyMM,FinkMP,MarshallJC,AbrahamE,AngusD,CookD,CohenJ,OpalSM,VincentJL,RamsayG,FortheInternationalSepsisDefinitionsConference.2001SCCM/ESICM/ACCP/ATS/SISInternationalSepsisDefinitionsConference.CritCareMed2003;31:1250-1256,全身性感染(sepsis):改变定义的原因,诊断标准应当普遍适用于临床医疗及临床试验具有较高的敏感性和特异性避免过于复杂以至难以记忆或应用采用普遍应用的试验指标适用于成人,儿童和新生儿,LevyMM,FinkMP,MarshallJC,AbrahamE,AngusD,CookD,CohenJ,OpalSM,VincentJL,RamsayG,FortheInternationalSepsisDefinitionsConference.2001SCCM/ESICM/ACCP/ATS/SISInternationalSepsisDefinitionsConference.CritCareMed2003;31:1250-1256,全身性感染(sepsis):流行病学,MartinGS,ManninoDM,StephanieEatonS,etal.TheEpidemiologyofSepsisintheUnitedStatesfrom1979through2000.NEnglJMed2003;348:1546-54.,全身性感染(sepsis):流行病学,致病菌革兰阳性菌平均每年增加26.3%真菌1979年5,231例2000年16,042例增加207%,MartinGS,ManninoDM,StephanieEatonS,etal.TheEpidemiologyofSepsisintheUnitedStatesfrom1979through2000.NEnglJMed2003;348:1546-54.,全身性感染(sepsis):流行病学,MartinGS,ManninoDM,StephanieEatonS,etal.TheEpidemiologyofSepsisintheUnitedStatesfrom1979through2000.NEnglJMed2003;348:1546-54.,全身性感染流行病学:USA19792000,ICD-9有关全身性感染的编码500家急性病医院750,000,000住院患者10,319,418例全身性感染/22年,全身性感染发病率的推算,平均每年增加1.5%;相当于年增新发病例约22,875例AngusDC,etal.TheepidemiologyofseveresepsisintheUnitedStates:Analysisofincidence,outcomeandassociatedcostsofcare.,全身性感染临床试验对照组的病死率,全身性感染与严重全身性感染,严重全身性感染:与常见病的比较,NationalCenterforHealthStatistics,2001.AmericanCancerSociety,2001.*AmericanHeartAssociation.2000.AngusDCetal.CritCareMed.2001(InPress).,严重全身性感染与其他死因,全身性感染的医疗费用,2000年ICU医疗费用的40%欧洲每年花费7,600,000,0001美国每年花费$16,700,000,0002,DaviesAetal.Abstract581.14thAnnualCongressoftheEuropeanSocietyofIntensiveCareMedicine,Geneva,Switzerland,30September-3October2001AngusDC,Linde-ZwirbleWT,LidickerJ,etal.EpidemiologyofseveresepsisintheUnitedStates:Analysisofincidence,outcome,andassociatedcostsofcare.CritCareMed2001;29:13031310,SurvivingSepsisCampaign:Why?,过去5年间阳性结果的干预措施严重全身性感染与感染性休克EGDT激素APC小潮气量通气策略危重病患者的一般治疗镇静严格血糖控制脱机方案,严重全身性感染循证医学指南,SurvivingSepsisCampaign(SSC)GuidelinesforManagementofSevereSepsisandSepticShock,DellingerRP,CarletJM,MasurH,GerlachH,CalandraT,CohenJ,Gea-BanaclocheJ,KehD,MarshallJC,ParkerMM,RamsayG,ZimmermanJL,VincentJL,LevyMMandtheSSCManagementGuidelinesCommitteeCritCareMed2004;32:858-873IntensiveCareMed2004;30:536-555sepsisforumTheguidelineswerepublishedinbothCriticalCareMedicineandinIntensivecareMedicine,andareavailableon-line,SurvivingSepsisCampaignGuidelinesForManagementOfSevereSepsis/SepticShock,TheFirstRevisionAPreliminaryReport,SurvivingSepsisCampaignGuideline,最初复苏(initialresuscitation)诊断(diagnosis)抗生素治疗(antibiotictherapy)感染源控制(sourcecontrol)液体治疗(fluidtherapy)升压药物(vasopressors)强心药物(inotropictherapy)激素(steroids)活化蛋白C(recombinanthumanactivatedproteinC)血液制品(bloodproductadministration),ARDS机械通气(mechanicalventilationofsepsis-inducedALI/ARDS)镇静(sedation,analgesia,andNMBinsepsis)血糖控制(glucosecontrol)肾脏替代(renalreplacement)碳酸氢钠(bicarbonatetherapy)DVT预防(DVTprophylaxis)应激性溃疡预防(stressulcerprophylaxis)考虑限制支持治疗水平(considerationforlimitationofsupport),SurvivingSepsisCampaignGuideline,最初复苏(initialresuscitation)诊断(diagnosis)抗生素治疗(antibiotictherapy)感染源控制(sourcecontrol)液体治疗(fluidtherapy)升压药物(vasopressors)强心药物(inotropictherapy)激素(steroids)活化蛋白C(recombinanthumanactivatedproteinC)血液制品(bloodproductadministration),ARDS机械通气(mechanicalventilationofsepsis-inducedALI/ARDS)镇静(sedation,analgesia,andNMBinsepsis)血糖控制(glucosecontrol)肾脏替代(renalreplacement)碳酸氢钠(bicarbonatetherapy)DVT预防(DVTprophylaxis)应激性溃疡预防(stressulcerprophylaxis)考虑限制支持治疗水平(considerationforlimitationofsupport),推荐意见的评级系统,SackettDL.Chest1989;95:2S-4SSprungCL,BernardGR,DellingerRP.IntensiveCareMed2001;27(Suppl):S1-S2,推荐意见的评级系统GRADE,证据的质量评估指标试验设计一致性直接性(对所研究的问题)偏倚的报告评估级别A高质量B中等质量C低质量D极低质量,推荐的强度1:强烈推荐方法学缺陷较少作用较大副作用较少2:一般推荐方法学缺陷较多评价不确切作用较小明显增加危害,工作负担,医疗费用,SurvivingSepsisCampaignGuideline推荐意见(n=46),最初的复苏治疗,发生全身性感染诱发的低血压时低血压乳酸酸中毒,乳酸清除率与感染性休克预后,严重全身感染与感染性休克预后的独立危险因素乳酸清除率OR0.98995%CI0.9780.999p=.04,NguyenHB,RiversEP,KnoblichBP,JacobsenG,MuzzinA,ResslerJA,TomlanovichMC.Earlylactateclearanceisassociatedwithimprovedoutcomeinseveresepsisandsepticshock.CritCareMed2004;32:1637-1642.,隐性低灌注与创伤预后,TheGoldenHourandtheSilverDay入选标准:成年创伤患者存活时间24小时ISS20血流动力学稳定SBP100HR1mL/kg/h乳酸2.5mmol/L或其他灌注不足表现,BlowO,MaglioreL,ClaridgeJ,ButlerK,YoungJ.TheGoldenHourandtheSilverDay:DetectionandCorrectionofOccultHypoperfusionwithin24HoursImprovesOutcomefromMajorTrauma.JTrauma1999;47(5):964,隐性低灌注与创伤预后,BlowO,MaglioreL,ClaridgeJ,ButlerK,YoungJ.TheGoldenHourandtheSilverDay:DetectionandCorrectionofOccultHypoperfusionwithin24HoursImprovesOutcomefromMajorTrauma.JTrauma1999;47(5):964,严重创伤患者两次LA2.5,输注液体或血液制品,重复LA2.5,Swan-Ganz,动脉插管,肾脏剂量多巴胺,将PCWP提高到1215将Hct提高到30%,重复LA2.5,升压药物(多巴酚丁胺)心脏超声检查,若LA仍2.5,隐性低灌注与创伤预后,BlowO,MaglioreL,ClaridgeJ,ButlerK,YoungJ.TheGoldenHourandtheSilverDay:DetectionandCorrectionofOccultHypoperfusionwithin24HoursImprovesOutcomefromMajorTrauma.JTrauma1999;47(5):964,全身性感染的诊断,适当的培养至少留取2个血培养1个外周血培养每个留置48h的血管通路留取1个血培养(GradeD),抗生素治疗前后血培养的阳性率,139名患者,抗生素治疗前,抗生素治疗过程中,开始抗生素治疗,83名患者(60%)血培养阴性或分离出污染菌,0/83(0%)分离到致病菌,56名患者(40%)分离到致病菌,26/56(45%)分离到致病菌,25名患者(45%)分离到致病的葡萄球菌,19/25(76%)分离到葡萄球菌,14名患者(25%)分离到致病的链球菌,5/14(36%)分离到链球菌,17名患者(30%)分离到革兰阴性杆菌,2/17(12%)分离到革兰阴性杆菌,1/139(0.72%)分离到新的致病菌,GraceCJ,LiebermanJ,PierceK,etal.UsefulnessofBloodCultureforHospitalizedPatientsWhoAreReceivingAntibioticTherapy.ClinInfectDis2001;32:1651-5,临床意义,应用抗生素前进行血培养分离到致病菌的可能性增加2.2倍在开始抗生素治疗最初72小时内,连续进行血培养的结果,可以根据应用抗生素前血培养的结果预测极少分离到新的致病菌医生可以等待应用抗生素前的血培养结果回报后,再进行新的血培养,GraceCJ,LiebermanJ,PierceK,etal.UsefulnessofBloodCultureforHospitalizedPatientsWhoAreReceivingAntibioticTherapy.ClinInfectDis2001;32:1651-5,抗生素治疗,确诊严重全身性感染后1小时内开始静脉抗生素治疗1C(GradeE),早期应用抗生素与感染患者病死率,KumarA,RobertsD,WoodKE,etal.Durationofhypotensionbeforeinitiationofeffectiveantimicrobialtherapyisthecriticaldeterminantofsurvivalinhumansepticshock.CritCareMed2006;34:1589-1596,早期应用抗生素与感染患者病死率,KumarA,RobertsD,WoodKE,etal.Durationofhypotensionbeforeinitiationofeffectiveantimicrobialtherapyisthecriticaldeterminantofsurvivalinhumansepticshock.CritCareMed2006;34:1589-1596,持续低血压或乳酸4mmol/L最初的复苏治疗,最初6小时内达到的目标CVP812mmHgMAP65mmHgUO0.5ml/kg/hrScvO270%1B(GradeB),感染性休克:灌注压与组织灌注,LeDoux,AstizME,CarpatiCM,RackowED.Effectsofperfusionpressureontissueperfusioninsepticshock.CritCareMed2000;28:2729-2732,影响感染性休克预后的循环指标,目的:确定与预后相关的血流动力学指标的适当阈值设计:回顾性队列研究19992002年,治疗的最初48小时,分析6和48小时结果:病死率33%单因素分析及逻辑回归分析入院时的MAP和乳酸水平48小时的MAP,SvO234g/dl或上升9g/dl血浆皮质醇15g/dl或上升9g/dl,全身性感染:相对性肾上腺皮质功能不全(RAI),相对性肾上腺皮质功能不全与病死率,AnnaneD,SbilleV,TrochG,etal.:A3-levelprognosticclassificationinsepticshockbasedoncortisollevelsandcortisolresponsetocorticotropin.JAMA2000,283:1038-1045,感染性休克的激素替代治疗,入选标准明确的感染灶休克发生38.3C或90bpmSBP5g/kg/min)或NE或EpiUO2mmol/L机械通气,治疗治疗组氢化可的松50mgivq6h9-氟氢可的松50gqd安慰剂组疗程7天,AnnaneD,SebilleV,CharpentierC,etal.Effectoftreatmentwithlowdosesofhydrocortisoneandfludrocortisoneonmortalityinpatientswithsepticshock.JAMA2002;288:862-71.,感染性休克的激素替代治疗,AnnaneD,SebilleV,CharpentierC,etal.Effectoftreatmentwithlowdosesofhydrocortisoneandfludrocortisoneonmortalityinpatientswithsepticshock.JAMA2002;288:862-71.,感染性休克的激素替代治疗,AnnaneD,SebilleV,CharpentierC,etal.Effectoftreatmentwithlowdosesofhydrocortisoneandfludrocortisoneonmortalityinpatientswithsepticshock.JAMA2002;288:862-71.,感染性休克的激素替代治疗,AnnaneD,SebilleV,CharpentierC,etal.Effectoftreatmentwithlowdosesofhydrocortisoneandfludrocortisoneonmortalityinpatientswithsepticshock.JAMA2002;288:862-71.,激素与感染:尚待阐明的问题,患者选择严重感染vs.感染性休克用药时机发病8小时vs.72小时激素疗程是否减量预后指标休克逆转vs.病死率,激素骤停可使细胞因子增加,KehD,BoehnkeT,Weber-CartensS,etal.Immunologicandhemodynamiceffectsoflow-dosehydrocortisoneinsepticshock:adouble-blind,randomized,placebo-controlled,crossoverstudy.AmJRespirCritCareMed.2003;167:512-520,重组人活化蛋白C,死亡高危APACHEII25感染诱发的多器官功能衰竭感染性休克感染诱发的ARDS无绝对禁忌症权衡相对禁忌症(GradeB),全身性感染:活化蛋白C,BernardGR,VincentJL,LaterrePF,etal.EfficacyandsafetyofrecombinanthumanactivatedproteinCforseveresepsis.NEnglJMed2001;344:699-709.,安慰剂(n=840),活化蛋白C(n=850),绝对病死率下降6.1%,全身性感染:活化蛋白C,BernardGR,VincentJL,LaterrePF,etal.EfficacyandsafetyofrecombinanthumanactivatedproteinCforseveresepsis.NEnglJMed2001;344:699-709.,APACHEII四分位与病死率,BernardGR,VincentJL,LaterrePF,etal.EfficacyandsafetyofrecombinanthumanactivatedproteinCforseveresepsis.NEnglJMed2001;344:699-709.,26:33,57:49,58:48,118:80,衰竭脏器数目与病死率,BernardGR,VincentJL,LaterrePF,etal.Drotrecoginalfa(activated)(recombinanthumanactivatedproteinC)forthetreatmentofseveresepsis.CritCareMed2003;31Suppl:S85-S90.,全身性感染:活化蛋白C,PROWESSRandomized,double-blinded,placebo-controlledKnownorsuspectedinfection,SIRScriteria3;organdysfunction128-daymortalityrate:30.8%vs.24.7%(p=0.005)ADDRESSRandomized,double-blinded,placebo-controlledSeveresepsis,APACHEII25,orsingle-organfailure28-daymortalityrate:17.0%vs.18.5%(p=0.34)ENHANCESingle-arm,open-labelKnownorsuspectedinfection,SIRScriteria3;organdysfunction128-daymortalityrate:25.3%,全身性感染:活化蛋白C,WiedermannCJ,KaneiderNC.Ameta-analysisofcontrolledtrialsofrecombinanthumanactivatedproteinCtherapyinpatientswithsepsis.BMCEmergencyMedicine2005;5:7,全身性感染:活化蛋白C,EichackerPQ,DannerRL,SuffrediniAF,CuiX,NatansonC.ReassessingrecombinanthumanactivatedproteinCforsepsis:Timeforanewrandomizedcontrolledtrial.CritCareMed2005;33(10):2426-2428,全身性感染:活化蛋白C,EichackerPQ,DannerRL,SuffrediniAF,CuiX,NatansonC.ReassessingrecombinanthumanactivatedproteinCforsepsis:Timeforanewrandomizedcontrolledtrial.CritCareMed2005;33(10):2426-2428,血糖控制,病情稳定后血糖150mg/dL持续输注胰岛素和葡萄糖监测最初每3060分钟稳定后q4h(GradeD),血糖控制,血糖控制非常重要最初病情稳定后静脉输注胰岛素1B目标范围?血糖150mg/dL2C血糖控制方案2C葡萄糖热卡及监测1B,外科患者的强化胰岛素治疗,高血糖与胰岛素抵抗现象十分普遍伴有AMI的糖尿病患者,控制血糖水平215mg/L,长期预后得以显著改善1,2vandenBerghe等人对1548名危重病患者进行了随机对照试验,以评价强化胰岛素治疗及传统血糖控制方法对危重病患者的影响3,MalmbergK.BMJ1997;314:1512-5MalmbergK.Circulation1999;99:2626-2632VandenBergheG,etal.NEnglJMed2001;345:1359-1367,外科患者的强化胰岛素治疗,试验设计入住外科ICU的机械通气患者所有患者接受200300g葡萄糖/天入ICU当日TPN总热卡的6080%为葡萄糖提供对照组:控制血糖180200mg/dl治疗组:控制血糖80110mg/dl,VanDenBergheG,WoutersP,WeekersF,etal.:Intensiveinsulintherapyinthecriticallyillpatients.NEnglJMed2001,345:1359-1367,外科患者的强化胰岛素治疗,至随访第12个月,强化胰岛素治疗可以降低病死率3.4%(p4mmol/L(36mg/dl)时:最初应用晶体液至少20ml/kg(或等量的胶体液)最初液体复苏无效时应用升压药物以维持MAP65mmHg经过液体复苏后仍持续低血压(感染性休克)和(或)乳酸4mmol/L(36mg/dl):使CVP8mmHg使ScvO270%,SepsisResuscitationBundle(应在最初6小时内达到),B.测定血清乳酸水平D.应用抗生素前留取血培养E.入急诊室3小时或入ICU1小时内应用抗生素E.低血压和(或)乳酸4mmol/L(36mg/dl)时:最初应用晶体液至少20ml/kg(或等量的胶体液)最初液体复苏无效时应用升压药物以维持MAP65mmHgB.经过液体复苏后仍持续低血压(感染性休克)和(或)乳酸4mmol/L(36mg/dl):使CVP8mmHg使ScvO270%,SepsisManagementBundle(应在最初24小时内达到),对感染性休克患者根据ICU标准化规定应用小剂量激素根据ICU标准化规定应用活化蛋白C控制血糖水平正常值下限,且150mg/dl(8.3mmol/L)维持机械通气患者吸气平台压力30cmH2O,SepsisManagementBundle(应在最初24小时内达到),C.对感染性休克患者根据ICU标准化规定应用小剂量激素B.根据ICU标准化规定应用活化蛋白CD.控制血糖水平正常值下限,且150mg/dl(8.3mmol/L)B.维持机械通气患者吸气平台压力30cmH2O,SurvivingSepsisCampaignInitialResultsReportingtheGapbetweenPerceptionandPractice,WhatWeThinkWeDovs.WhatWeActuallyDo,ARDS保护性通气策略ARDSnet,TheAcuteRespiratoryDistressSyndromeNetwork:Ventilationwithlowertidalvolumesascomparedwithtraditionaltidalvolumesforacutelunginjuryandtheacuterespiratorydistresssyndrome.NEnglJMed2000;342:1301-1308,ARDS保护性通气策略ARDSnet,TheAcuteRespiratoryDistressSyndromeNetwork:Ventilationwithlowertidalvolumesascomparedwithtraditionaltidalvolumesforacutelunginjuryandtheacuterespiratorydistresssyndrome.NEnglJMed2000;342:1301-1308,P=0.007,研究结果的发表对日常工作并无影响,RubenfeldGD,etal.AmJRespirCritCareMed2001;163:A295,P=0.11,P=0.02,研究结果的发表对日常工作并无影响,BrowerRG,etal.AmJRespirCritCareMed2004;169(suppl):A256,ARDSNetworkPaperPublishedNEJM,实施保护性通气策略的障碍,RubenfeldGD,CooperC,CarterG,ThompsonBT,HudsonLD.Barrierstoprovidinglung-protectiveventilationtopatientswithacutelunginjury.CritCareMed2004;32:1289-1293,Adhereto“BestPractice”?,Doyouuselungprotectivestrategyinventilatingacutelunginjurypatients?,BrunkhorstFM,etal,fortheGermanCompetenceNetworkSepsisSepNet.Thegapbetweenperceptionandpracticeofsepsistherapy.(submitted),Adhereto“BestPractice”?,ResultsofNon-ScriptedCareProcesses,BrunkhorstFM,etal,fortheGermanCompetenceNetworkSepsisSepNet.Thegapbetweenperceptionandpracticeofsepsistherapy.(submitted),SupportiveandAdjunctiveTherapiesResultsoftheGerman“Prevalence”Study,BrunkhorstFM,etal,fortheGermanCompetenceNetworkSepsisSepNet.Thegapbetweenperceptionandpracticeofsepsistherapy.(submitted),为何循证治疗在ICU中应用并不普遍,缺乏相关知识医疗费用报销的限制,繁忙的工作安排ICU医生的怀疑危重病领域众多的阴性试验结果对证据的主观选择临床惰性不能正确鉴别患者医疗资源的配置,VHA19-ICUSepsisBundles,69%Reduction(p0.001),36%Reduction(NS),PronovostP,2005,SepsisBundle,101名严重全身性感染患者符合6小时Bundle普通病房:90(89%)急诊科:11(11%),71名收入ICU符合24小时Bundle:69(98%),43(61%)转出ICU,28(39%)死于ICU,35(81%)存活,8(19%)死亡,65(64%)存活,36(36%)死亡,GaoF,MelodyT,DanielsDF,GilesS,FoxS.Theimpactofcompliancewith6-hourand24-hoursepsisbundlesonhospitalmortalityinpatientswithseveresepsis:aprospectiveobservationalstudy.CriticalCare2005,9:R764-R770(DOI10.1186/cc3909),SepsisBundle,符合6小时Bundle(n=101),符合24小时Bundle(n=69),52%(52/101),30%(21/69),依从率,GaoF,MelodyT,DanielsDF,GilesS,FoxS.Theimpactofcompliancewith6-hourand24-hoursepsisbundlesonhospitalmortalityinpatientswithseveresepsis:aprospectiveobservationalstudy.CriticalCare2005,9:R764-R770(DOI10.1186/cc3909),SepsisBundle(6hour),RR2.12(1.203.76)P=0.01NNT=3.9,GaoF,MelodyT,DanielsDF,GilesS,FoxS.Theimpactofcompliancewith6-hourand24-hoursepsisbundlesonhospitalmortalityinpatientswithseveresepsis:aprospectiveobservationalstudy.CriticalCare2005,9:R764-R770(DOI10.1186/cc3909),SepsisBundl