1、孙仁华浙江省人民(RNMN)医院ICU2016-10,脓毒症3.0“面面观”,第一页，共四十二页。,严重(ynzhng)脓毒症及脓毒性休克流行病学,严重脓毒症患者死亡(swng)风险为34%，脓毒性休克患者死亡风险为50%。,第二页，共四十二页。,新近流调显示(xinsh)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(xijing)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.2014 Apr 2;311(13):1308-16.,第三页，共四十二页。,脓毒症定义(dngy)变迁（1.0）,Se
2、psis 1.0=感染(gnrn)SIRS,Chest 1992 Jun;101(6):1644-55,第四页，共四十二页。,脓毒症定义(dngy)变迁（2.0）,Intensive Care Med.2003 Apr;29(4):530-8.Epub 2003 Mar 28.,Sepsis 2.0=感染SIRS会议提出(t ch)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。,第五页，共四十二页。,Diagnostic criteria for sepsis,第六页，共四十二页。
3、,The PIRO system for staging sepsis,第七页，共四十二页。,2012,SSC指南(zhnn)发展,Critical care medicine 2004 Mar;32(3):858-73.Critical care medicine 2008 Jan;36(1):296-327.Crit Care Med.2013 Feb;41(2):580-637.,2008,2004,第八页，共四十二页。,脓毒症诊断标准(biozhn)的“争议”,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
4、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：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(ln chun)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遗漏约 1/8 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，这提示当前脓毒症的筛查标准的特异性不佳。,N Engl J Med,2015,372(17):1629-1638.,第九页，共四十二页。,D
5、o we need a new definition of sepsis?,the definition of septic shock currently revolves around variable blood pressure and/or lactate levels,with loosely termed or undefined adequacy of fluid resuscitation and persistent hypotension.Defining sepsis must,however,be an ongoing iterative process requir
6、ing minor or major revisions as new findings come to light.In much the same way that software enhancements move from version 1.0 to 1.1 or to 2.0 depending on the magnitude of change,so a new sepsis 3.0 definition must be refined into versions 3.1,3.2,and so on until an eventual complete overhaul ge
7、nerates the development of sepsis 4.0.,Intensive Care Med,2015,41(5):909-911.,脓毒症的诊断标准于1991年发布（脓毒症1.0）,但过于(guy)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。,第十页，共四十二页。,脓毒症3.0.2016年,第十一页，共四十二页。,Sepsis 3.0“应运而生(yng yn r shng)”,JAMA.2016 Feb 23;315(8):801-10,第十二页，共四十二页。,Sepsis 3.0定义(dngy),JAMA.2016
8、Feb 23;315(8):801-10,Mortality 10%,第十三页，共四十二页。,Sepsis 3.0InfectionSOFA2,Sepsis 3.0诊断(zhndun)标准,JAMA.2016 Feb 23;315(8):801-10,第十四页，共四十二页。,Septic shock 定义(dngy)及诊断标准,JAMA.2016 Feb 23;315(8):801-10,Mortality 40%,Septic shock=Sepsis+输液(shy)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
9、 of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.,第十五页，共四十二页。,脓毒症3.0诊断(zhndun)流程,JAMA.2016 Feb 23;315(8):801-10,第十六页，共四十二页。,Sepsis 3.0,第十七页，共四十二页。,ACCP反对(fndu)Sepsis 3.0,1.Given that use of the current definitions
10、 results in saving lives,it seems unwise to change course in midstream by shifting the definition.This is especially true because there is still no known precise pathophysiological feature that defines sepsis.,2.Abandoning the use of SIRS to focus on findings that are more highly predictive of death
11、 could encourage waiting,rather than early,aggressive intervention.This is a mistake that we cannot make.,3.To abandon one system of recognizing sepsis because it is imperfect and not yet in universal use for another system that is used even less seems unwise without prospective validation of the ne
12、w systems utility.,Chest 2016 Feb,第十八页，共四十二页。,ACCP反对(fndu)Sepsis 3.0,4.What patients need is that we continue to build on the momentum of the last two decades and that we not disrupt it by conflating change with progress.,5.Our principal concern is that the new definition de-emphasizes intervention
13、at earlier stages of sepsis when the syndrome is actually at its most treatable.We believe that adopting a more restrictive definition that requires further progression along the sepsis pathway may delay intervention in this highly time-dependent condition,with additional risk to patients.,Chest 201
14、6 Feb,第十九页，共四十二页。,精准(jn zhn)医学下的Sepsis 3.0不足,“Definition”versus“Clinical Criteria”.(1)Sepsis researchers,both bench and clinical,should consider how their findings might validate or invalidate the new definition;(2)Clinicians should determine if the clinical criteria are useful in their own practice
15、s and consider what additional elements ought to be tested;(3)sooner rather than later.,Critical care medicine 2016 May;44(5):857-8.,第二十页，共四十二页。,“Dependent and Independent Variables”.Sepsis=(life-threatening)(organ dysfunction)(dysregulated host response)(infection).(1)Dont assume that the sequence
16、of events identified in the new definition reflects pathobiological reality,because no one really knows how things are ordered and connected;(2)Dont assume that the predominant abnormality in sepsis is immunologicalthat hypothesis has dominated both mechanistic and therapeutic investigation for over two decades,and has yet to bear fruit.,Critical care medicine 2016 May;44(5):857-8.,精准医学(yxu)下的Sepsis 3.0不足,第二十一页，共四十二页。,精准医学(yxu)下的Sepsis 3.0不足,“Appropriate comparators”.(1)We need to reconsider jus