脓脓毒毒症症2024/7/29严重脓毒症及脓毒性休克流行病学严重脓毒症患者死亡风险为34%，脓毒性休克患者死亡风险为50%。2024/7/29新近流调显示脓毒性休克死亡率下降结果发现，重症感染患者的绝对死亡率从35.0%下降到了18.4%，总死亡率下降了16.6%，年绝对死亡率下降了1.3%，相对风险下降了47.5%。JAMA.2014Apr2;311(13):1308-16.2024/7/29脓毒症定义变迁（1.0）Sepsis1.0=感染SIRSChest1992Jun;101(6):1644-55创伤创伤烧伤烧伤胰腺炎胰腺炎缺血缺血SIRSSIRSsepsisSEVERESEPSIS细菌细菌其他其他病毒病毒原虫原虫真菌真菌其他其他INFECTIONINFECTION2024/7/29脓毒症定义变迁（2.0）IntensiveCareMed.2003Apr;29(4):530-8.Epub2003Mar28.Sepsis 2.0=感染SIRS会议提出了包括20余条临床症状和体征评估指标构成的诊断标准，即Sepsis 2.0。然而该标准过于复杂，且缺乏充分的研究基础和科学研究证据支持，并未得到临床认可和应用。创伤创伤烧伤烧伤胰腺炎胰腺炎缺血缺血SIRSSIRSsepsisSEVERESEPSIS细菌细菌其他其他病毒病毒原虫原虫真菌真菌其他其他INFECTIONINFECTION2024/7/29Diagnosticcriteriaforsepsis2024/7/29ThePIROsystemforstagingsepsis2024/7/292012SSC指南发展Criticalcaremedicine2004Mar;32(3):858-73.Criticalcaremedicine2008Jan;36(1):296-327.CritCareMed.2013Feb;41(2):580-637.200820042024/7/29脓毒症诊断标准的“争议”方法：方法：通过对2000年至2013年澳大利亚和新西兰172个重症加强治疗病房(ICU)近120万例患者的数据分析，根据是否满足2条全身炎症反应综合征(SIRS)的诊断标准将感染伴器官功能障碍的患者分为SIRS阳性和SIRS阴性两组。结果：结果：在近11万例感染伴器官功能障碍的患者中，87.9%为SIRS阳性，12.1%为SIRS阴性，在14年内两组患者的临床特征和病死率变化相似。校正分析显示，患者病死率随着满足SIRS标准项目的增加呈线性增高。结论：该研究说明现有脓毒症标准有可能结论：该研究说明现有脓毒症标准有可能遗漏约遗漏约 1/8 的感染伴器官功能障碍患者的感染伴器官功能障碍患者，且该标准不能确定病死率增加的临界点，且该标准不能确定病死率增加的临界点，这提示当前脓毒症的筛查标准的特异性不这提示当前脓毒症的筛查标准的特异性不佳。佳。NEnglJMed,2015,372(17):1629-1638.2024/7/29Doweneedanewdefinitionofsepsis?thedefinitionofsepticshockcurrentlyrevolvesaroundvariablebloodpressureand/orlactatelevels,withlooselytermedorundefinedadequacyoffluidresuscitationandpersistenthypotension.Definingsepsismust,however,beanongoingiterativeprocessrequiringminorormajorrevisionsasnewfindingscometolight.Inmuchthesamewaythatsoftwareenhancementsmovefromversion1.0to1.1orto2.0dependingonthemagnitudeofchange,soa new sepsis 3.0 definition mustberefinedintoversions3.1,3.2,andsoonuntilaneventualcompleteoverhaulgeneratesthedevelopmentofsepsis4.0.IntensiveCareMed,2015,41(5):909-911.脓毒症的诊断标准于19911991年发布发布（脓毒症1.0）,但过于敏感，可能导致脓毒症的过度诊断和治疗；2001年更新版（脓毒症2.0）又过于复杂，未被广泛应用，未被广泛应用。 2024/7/29Sepsis3.0“应运而生”JAMA.2016Feb23;315(8):801-102024/7/29Sepsis3.0定义JAMA.2016Feb23;315(8):801-10Mortality10%2024/7/29Sepsis3.0InfectionSOFA2Sepsis3.0诊断标准JAMA.2016Feb23;315(8):801-102024/7/29Septicshock定义及诊断标准JAMA.2016Feb23;315(8):801-10Mortality40%Septic shock=Sepsis+输液无反应低血压+使用缩血管药物维持MAP65mmHg）+乳酸则2mmol/L。Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. 2024/7/29脓毒症3.0诊断流程JAMA.2016Feb23;315(8):801-102024/7/29ACCP反对Sepsis3.01.Giventhatuseofthecurrentdefinitionsresultsinsavinglives,itseemsunwisetochangecourseinmidstreambyshiftingthedefinition.Thisisespeciallytruebecausethereisstillnoknownprecisepathophysiologicalfeaturethatdefinessepsis.2.AbandoningtheuseofSIRStofocusonfindingsthataremorehighlypredictiveofdeathcouldencouragewaiting,ratherthanearly,aggressiveintervention.Thisisamistakethatwecannotmake.3.Toabandononesystemofrecognizingsepsisbecauseitisimperfectandnotyetinuniversaluseforanothersystemthatisusedevenlessseemsunwisewithoutprospectivevalidationofthenewsystemsutility.Chest2016Feb2024/7/29ACCP反对Sepsis3.04.Whatpatientsneedisthatwecontinuetobuildonthemomentumofthelasttwodecadesandthatwenotdisruptitbyconflatingchangewithprogress.5.Ourprincipalconcernisthatthenewdefinitionde-emphasizesinterventionatearlierstagesofsepsiswhenthesyndromeisactuallyatitsmosttreatable.Webelievethatadoptingamorerestrictivedefinitionthatrequiresfurtherprogressionalongthesepsispathwaymaydelayinterventioninthishighlytime-dependentcondition,withadditionalrisktopatients.Chest2016Feb2024/7/29精准医学下的Sepsis3.0不足“Definition” versus “Clinical Criteria”. (1)Sepsisresearchers,bothbenchandclinical,shouldconsiderhowtheirfindingsmightvalidateorinvalidatethenewdefinition;(2)Cliniciansshoulddetermineiftheclinicalcriteriaareusefulintheirownpracticesandconsiderwhatadditionalelementsoughttobetested;(3)soonerratherthanlater.Criticalcaremedicine2016May;44(5):857-8.2024/7/29“Dependent and Independent Variables”. Sepsis = (life-threatening)(organ dysfunction)(dysregulated host response)(infection). (1)Dontassumethatthesequenceofeventsidentifiedinthenewdefinitionreflectspathobiologicalreality,becausenoonereallyknowshowthingsareorderedandconnected;(2)Dontassumethatthepredominantabnormalityinsepsisisimmunologicalthathypothesishasdominatedbothmechanisticandtherapeuticinvestigationforovertwodecades,andhasyettobearfruit.Criticalcaremedicine2016May;44(5):857-8.精准医学下的精准医学下的Sepsis 3.0不足不足2024/7/29精准医学下的Sepsis3.0不足“Appropriate comparators”. (1)Weneedtoreconsiderjustwhatconstitutesanappropriatecontrolforsepsisresearch;(2)Attheveryleast,weoughttomakesurethatstudiescharacterizingsepsisinanimalmodelsandinpatientsusesimilarcontrols.“What comes next?”.Howand how soondo we initiate Sepsis-4.0? I dont knowbut lets not wait a decade and a half this time.Criticalcaremedicine2016May;44(5):857-8.2024/7/29Problem#1:Sepsis-IIIremainssubjectiveSepsis3.0的10个疑问（一）所有定义都包含了所有定义都包含了“suspected infection”，但怎么去界定但怎么去界定“suspected infection”却很难。却很难。2024/7/29Problem#2:qSOFA&SOFAaremortalitypredictors,nottestsforsepsisSepsis3.0的10个疑问（二）qSOFA & SOFA 评分多用评分多用于死亡预测，而非用于检测于死亡预测，而非用于检测sepsis。2024/7/29Problem#3:Sepsis-IIIislessspecificforinfectionthanSepsis-IISepsis3.0的10个疑问（三）Sepsis 3.0 对诊断感染特异对诊断感染特异性低于性低于Sepsis 2.0 。2024/7/29Problem#4:qSOFAhassimilarperformancecomparedtoSIRSformortalitypredictionSepsis3.0的10个疑问（四）事实上，事实上，qSOFA与与SIRS对对死亡预测价值相当死亡预测价值相当 。2024/7/29Problem#5:qSOFAmaybelessspecificindiseasesthatdirectlycausehypotension,tachypnea,ordeliriumSepsis3.0的10个疑问（五）2024/7/29Sepsis3.0的10个疑问（六）Problem#6:qSOFAisinconsistentwithavalidatedprognosticmodel(CURB65)CURB65模型被认为肺炎诊断经典模型。qSOFA与之比较，会高估肺炎的死亡率。2024/7/29Sepsis3.0的10个疑问（七）Problem#7:CombiningqSOFAandSOFAscoresisnotevidence-basedamongpatientsoutsidetheICUSOFA比qSOFA特异性更低，似乎不符合逻辑。2024/7/29Sepsis3.0的10个疑问（八）Problem#8:ThecombinedperformanceofqSOFA+SOFAformortalityisnotreported.2024/7/29Sepsis3.0的10个疑问（九）Problem#9:TheoverallsensitivityofSepsis-IIIforsepsismightbe50%outsideoftheICU2024/7/29Sepsis3.0的10个疑问（十）Problem#10:Sepsis-IIIisnotaconsensusguidelineintheUnitedStates支持团体：SocietyofCriticalCareMedicinetheAmericanThoracicSocietytheAmericanAssociationofCriticalCareNurses暂未支持团体：AmericanCollegeofChestPhysicianstheInfectiousDiseaseSocietyofAmericatheEmergencyMedicinesocietiesthehospitalmedicinesocieties2024/7/29脓毒症未来发展2024/7/29BMJ：Sepsis的病理生理及临床治疗作者综述5000多篇文献（引文217篇），复习了近35年来脓毒症的流行病学，危险因素、微生物学以及病因学及其治疗的研究成果，。综述对最新的Sepsis3.0也做了介绍和归纳，根据Sepsis3.0定义规定，脓毒症是由于对感染的不适当的宿主反应而产生的危及生命的脏器功能障碍，而Sepsis1.0或2.0说的是全身炎症反应，两者的差别决定了其病理生理的机制是不一致的。BMJ(Clinicalresearched.)2016353:i1585.2024/7/29BMJ:当前证据下的脓毒症诊治“取舍”BMJ(Clinicalresearched.)2016353:i1585.2024/7/29脓毒症未来发展方向脓毒症未来发展方向Whatistheoptimalfluidandvasopressorresuscitationstrategyintheearlyphaseofsepticshock?感染性休克早期阶段理想的液体与缩血管药物复苏策略？Willlungprotectiveventilationinpatientswithsepsisreducethedevelopmentofacuterespiratorydistresssyndrome?肺保护通气降低SEPSIS患者ARDS发展？Willnewtreatmentsreducetheincidenceofacutekidneyinjuryinpatientswithsepsis?新疗法降低SEPSIS患者AKI发生率？发展方向发展方向Canrapid,inexpensive,andspecificmicrobiologictestsfordefiningcausativepathogensbedevelopedusinggeneticandotherapproaches?快速、廉价、特异的方法如基因检测等可行吗？Willwedevelopneweffectiveandsafeantibioticsinaneraofincreasinglycommondrugresistantpathogens?耐药时代的新抗菌药物？BMJ(Clinicalresearched.)2016353:i1585.2024/7/29Howdoesthemicrobiomechangeinsepsisandhowmightthisbeleveragedtherapeutically?SEPSIS中微生物如何变化及如何因此调整治疗？Whatarethelongtermphysical,cognitive,andpsychosocialchangesinpatientswhosurvivesepsis,andcanwedevelopeffectiverehabilitativetechniques?SEPSIS存活者长期的躯体、认知、心里有何变化？有效康复技术？Canweimprovetheabilityofpreclinicalmodelsofsepsistopredicttherapeuticefficacy?改善SEPSIS临床前模型能力，预测治疗效果Canwedeveloparangeofpoint-of-carebiomarkerstogrouppatientswithsepsisintopathophysiologiccategories?Thiswouldimproveourunderstandingofthebiologyandmayenhanceclinicaltrialdesign能通过生物标志物对SEPSIS患者进行病理生理归类，从而加深认识提高临床研究的设计？Howwilltherecentlyreleaseddefinitionsandclinicalcriteriaforsepsisshapeitsclinicaldetection,treatment,andresearch?新标准对诊断、治疗、研究的影响？脓毒症未来发展方向脓毒症未来发展方向BMJ(Clinicalresearched.)2016353:i1585.2024/7/29小结 Sepsis 3.0支持者：支持者：1.较之旧定义，新定义简单明了，易于教学及理解；2.qSOFA专注于具有提示意义的主要脏器系统的症状和体征；3.qSOFA已经回顾性的大数据分析证明可信有效；4.qSOFA的敏感性与特异性优于既往的ICU环境之外应用的标准；5.新定义的发布及所引起的讨论有助于提高对该疾病的关注度。 Sepsis 3.0反对者：反对者：1.新定义强调的标准为“已知或疑似感染的患者”，但显然感染并非总能被发现，即使使用血培养；2.qSOFA在非ICU环境的应用有可能过于敏感；3.qSOFA与SOFA严格而言并非Sepsis的筛查工具，而应该是提示病死率增加的标志物；4.美国医疗保险中心（CMS）目前也尚未通过新的定义，而继续沿用Sepsis2.0；5.以上内容和定义不涉及第二科，换句话说，儿科目前缺乏相应应用。2024/7/29t h a n k s2024/7/29