The Third International Connsus Definitions for Sepsis and Septic Shock (Sepsis-3)
Mervyn Singer,MD,FRCP;Clifford S.Deutschman,MD,MS;Christopher Warren Seymour,MD,MSc;Manu Shankar-Hari,MSc,MD,FFICM;Djillali Annane,MD,PhD;Michael Bauer,MD;Rinaldo Bellomo,MD;Gordon R.Bernard,MD;Jean-Daniel Chiche,MD,PhD;Craig M.Coopersmith,MD;Richard S.Hotchkiss,MD;Mitchell M.Levy,MD;John C.Marshall,MD;Greg S.Martin,MD,MSc;
Steven M.Opal,MD;Gordon D.Rubenfeld,MD,MS;Tom van der Poll,MD,PhD;Jean-Louis Vincent,MD,PhD;Derek C.Angus,MD,MPH
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Author Affiliations:Author
affiliations are listed at the end of this article.
Group Information:The Sepsis Definitions Task Force members are the authors listed above.
Corresponding Author:Clifford S.Deutschman,MD,MS,Departments of Pediatrics and Molecular Medicine,Hofstra–Northwell School of Medicine,Feinstein Institute for Medical Rearch,269-0176th Ave,New Hyde Park,NY 11040(cdeutschman@nshs.edu ).
Special Communication |CARING FOR THE CRITICALLY ILL PATIENT
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S epsis,a syndrome of physiologic,pathologic,and bio-chemical abnormalities induced by infection,is a major
public health concern,accounting for more than$20bil-lion(5.2%)of total US hospital costs in2011.1The reported inci-dence of psis is increasing,2,3likely reflecting aging populations with more comorbidities,greater recognition,4and,in some coun-tries,reimburment-favorable coding.5Al
though the true inci-dence is unknown,conrvative estimates indicate that psis is a leading cau of mortality and critical illness worldwide.6,7Further-more,there is increasing awareness that patients who survive p-sis often have long-term physical,psychological,and cognitive dis-abilities with significant health care and social implications.8
A1991connsus conference9developed initial definitions that focud on the then-prevailing view that psis resulted from a host’s systemic inflammatory respon syndrome(SIRS)to infection(Box1).Sepsis complicated by organ dysfunction was termed vere psis,which could progress to ptic shock, defined as“psis-induced hypotension persisting despite adequate fluid resuscitation.”A2001task force,recognizing limi-tations with the definitions,expanded the list of diagnostic cri-teria but did not offer alternatives becau of the lack of support-ing evidence.10In effect,the definitions of psis,ptic shock, and organ dysfunction have remained largely unchanged for more than2decades.
The Process of Developing New Definitions
Recognizing the need to reexamine the current definitions,11the European Society of Intensive Care Medicine and the Society of Critical Care Medicine convened a task force of19critical care, infectious
dia,surgical,and pulmonary specialists in January 2014.Unrestricted funding support was provided by the societies, and the task force retained complete autonomy.The societies each nominated cochairs(Drs Deutschman and Singer),who lected members according to their scientific experti in psis epidemiology,clinical trials,and basic or translational rearch.
The group engaged in iterative discussions via4face-to-face meetings between January2014and January2015,email corre-spondence,and voting.Existing definitions were revisited in light of an enhanced appreciation of the pathobiology and the avail-ability of large electronic health record databas and patient cohorts.
An expert connsus process,bad on a current under-standing of psis-induced changes in organ function,morphol-ogy,cell biology,biochemistry,immunology,and circulation (collectively referred to as pathobiology),forged agreement on updated definition(s)and the criteria to be tested in the clinical arena(content validity).The distinction between definitions and clinical criteria is discusd below.The agreement between potential clinical criteria(construct validity)and the ability of the criteria to predict outcomes typical of psis,such as need for intensive care unit(ICU)admission or death(predictive validity,a form of criterion validity),were then tested.The explorations were performed in multiple large electronic health record data-bas that also addresd the abnce(mis
口才是练出来的singness)of individual elements of different organ dysfunction scores and the question of generalizability(ecologic validity).12A systematic literature review and Delphi connsus methods were also ud for the definition and clinical criteria describing ptic shock.13 When compiled,the task force recommendations with sup-porting evidence,including original rearch,were circulated to major international societies and other relevant bodies for peer review and endorment(31endorsing societies are listed at the end of this article).
Issues Addresd by the Task Force
The task force sought to differentiate psis from uncomplicated infection and to update definitions of psis and ptic shock to be consistent with improved understanding of the pathobiology.A definition is the description of an illness concept;thus,a definition of psis should describe what psis“is.”This chon approach allowed discussion of biological concepts that are currently incom-pletely understood,such as genetic influences and cellular abnor-malities.The psis illness concept is predicated on infection as its trigger,acknowledging the current challenges in the microbiologi-cal identification of infection.It was not,however,within the task force brief to examine definitions of infection.
The task force recognized that psis is a syndrome without, at prent,a validated criterion standard diagnostic test.There is currently no process to operationalize the definitions of psis and ptic shock,a key deficit that has led to major variations in reported incidence and mortality rates(e later discussion).The task force determined that there was an important need for fea-tures that can be identified and measured in individual patients and sought to provide such criteria to offer uniformity.Ideally, the clinical criteria should identify all the elements of psis (infection,host respon,and organ dysfunction),be simple to obtain,and be available promptly and at a reasonable cost or bur-den.Furthermore,it should be possible to test the validity of the criteria with available large clinical data ts and,ultimately, prospectively.In addition,clinical criteria should be available to provide practitioners in out-of-hospital,emergency department, and hospital ward ttings with the capacity to better identify patients with suspected infection likely to progress to a life-threatening state.Such early recognition is particularly important becau prompt management of ptic patients may improve outcomes.4
In addition,to provide a more consistent and reproducible pic-ture of psis incidence and outcomes,the task force sought to in-tegrate the biology and clinical identification of psis with its epi-demiology and coding.
Clinical Review&Education Special Communication Connsus Definitions for Sepsis and Septic Shock
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Identified Challenges and Opportunities Asssing the Validity of Definitions
When There Is No Gold Standard
Sepsis is not a specific illness but rather a syndrome encompassing a still-uncertain pathobiology.At prent,it can be identified by a constellation of clinical signs and symptoms in a patient with sus-pec
ted infection.Becau no gold standard diagnostic test exists, the task force sought definitions and supporting clinical criteria that were clear and fulfilled multiple domains of ufulness and validity.weakness
Improved Understanding of Sepsis Pathobiology
Sepsis is a multifaceted host respon to an infecting pathogen that may be significantly amplified by endogenous factors.14,15The original conceptualization of psis as infection with at least2of the4SIRS criteria focud solely on inflammatory excess.How-ever,the validity of SIRS as a descriptor of psis pathobiology has been challenged.Sepsis is now recognized to involve early activa-tion of both pro-and anti-inflammatory respons,16along with major modifications in nonimmunologic pathways such as cardio-vascular,neuronal,autonomic,hormonal,bioenergetic,metabolic,
and coagulation,14,17,18all of which have prognostic significance. Organ dysfunction,even when vere,is not associated with sub-stantial cell death.19
The broader perspective also emphasizes the significant bio-logical and clinical heterogeneity in affected individuals,20with age,underlying comorbidities,concurrent injuries(including sur-gery)and medications,and source of infection adding further complexity.21This diversity cannot be appropriatel
y recapitulated in either animal models or computer simulations.14With further validation,multichannel molecular signatures(eg,transcriptomic, metabolomic,proteomic)will likely lead to better characterization of specific population subts.22,23Such signatures may also help to differentiate psis from noninfectious insults such as trauma or pancreatitis,in which a similar biological and clinical host respon may be triggered by endogenous factors.24Key concepts of psis describing its protean nature are highlighted in Box2.
Variable Definitions
A better understanding of the underlying pathobiology has been accompanied by the recognition that many existing terms(eg,p-sis,vere psis)are ud interchangeably,whereas others are redundant(eg,psis syndrome)or overly narrow(eg,pticemia). Inconsistent strategies in lecting International Classification of Dias,Ninth Revision(ICD-9),and ICD-10codes have com-pounded the problem.
Sepsis
The current u of2or more SIRS criteria(Box1)to identify psis was unanimously considered by the task force to be unhelpful. Changes in white blood cell count,temperature,and heart rate reflect infla全国英语等级考试网
mmation,the host respon to“danger”in the form of infection or other insults.The SIRS criteria do not necessarily indi-cate a dysregulated,life-threatening respon.SIRS criteria are prent in many hospitalized patients,including tho who never develop infection and never incur adver outcomes(poor dis-criminant validity).25In addition,1in8patients admitted to criti-cal care units in Australia and New Zealand with infection and new organ failure did not have the requisite minimum of2SIRS criteria to fulfill the definition of psis(poor concurrent validity)yet had protracted cours with significant morbidity and mortality.26 Discriminant validity and convergent validity constitute the2 domains of construct validity;the SIRS criteria thus perform poorly on both counts.
Organ Dysfunction or Failure
Severity of organ dysfunction has been assd with various scor-ing systems that quantify abnormalities according to clinical find-ings,laboratory data,or therapeutic interventions.Differences in the scoring systems have also led to inconsistency in reporting. The predominant score in current u is the Sequential Organ Fail-ure Asssment(SOFA)(originally the Sepsis-related Organ Failure Asssment27)(Table1).28A higher SOFA score is associated with an incread probability of mortality.28The score grades abnormal-ity by organ system and accounts for clinical interventions.How-ever,laboratory variables,namely,Pa O
2
,platelet count,creatinine level,and bilirubin level,are needed for full computation.Further-more,lection of variables and cutoff values were developed by connsus,and SOFA is not well known outside the critical care community.Other organ failure scoring systems exist,including systems built from statistical models,but none are in common u.
Septic Shock
Multiple definitions for ptic shock are currently in u.Further details are provided in an accompanying article by Shankar-Hari et al.13A systematic review of the operationalization of current definitions highlights significant heterogeneity in reported mortality.This heterogeneity resulted from differences in the clinical variables chon(varying cutoffs for systolic or mean blood pressure±diver levels of hyperlactatemia±vasopressor u±concurrent new organ dysfunction±defined fluid resuscita-tion volume/targets),the data source and coding methods,and enrollment dates.
傲慢与偏见电影台词
Connsus Definitions for Sepsis and Septic Shock Special Communication Clinical Review&Education
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导师英文A Need for Sepsis Definitions for the Public
and for Health Care Practitioners
Despite its worldwide importance,6,7public awareness of psis is poor.29Furthermore,the various manifestations of psis make di-agnosis difficult,even for experienced clinicians.Thus,the public needs an understandable definition of psis,whereas health care practitioners require improved clinical prompts and diagnostic ap-proaches to facilitate earlier identification and an accurate quanti-fication of the burden of psis.
Results/Recommendations
Definition of Sepsis
Sepsis is defined as life-threatening organ dysfunction caud by a dysregulated host respon to infection(Box3).This new defini-tion emphasizes the primacy of the nonhomeostatic host respon to infection,the potential lethality that is considerably in excess of a straightforward infection,and the need for urgent recognition.As described later,even a modest degree of organ dysfunction when infection is first suspected is associated with an in-hospital mortal-ity in excess of10%.Recognition of this condition thus merits a prompt and appropriate respon.
entire是什么意思Nonspecific SIRS criteria such as pyrexia or neutrophilia will con-tinue to aid in the general diagnosis of infection.The findings complement features of specific infections(eg,rash,lung consoli-dation,dysuria,peritonitis)thatfocusattentiontowardthelikelyana-tomical source and infecting organism.However,SIRS may simply reflect an appropriate host respon that is frequently adaptive.Sep-sis involves organ dysfunction,indicating a pathobiology more com-plex than infection plus an accompanying inflammatory respon alone.The task force emphasis on life-threatening organ dysfunc-tion is consistent with the view that cellular defects underlie physi-ologic and biochemical abnormalities within specific organ sys-tems.Under this terminology,“vere psis”becomes superfluous. Sepsis should generally warrant greater levels of monitoring and in-tervention,including possible admission to critical care or high-dependency facilities.
Clinical Criteria to Identify Patients With Sepsis
The task force recognized that no current clinical measures reflect the concept of a dysregulated host respon.However,as noted by the2001task force,many bedside examination findings and routine laboratory test results are indicative of inflammation or organ dysfunction.10The task force therefore evaluated which clinical criteria best identified infected patients most likely to have psis.This objective was achieved by interrogating large data ts of hospitalized patients with pres
umed infection, asssing agreement among existing scores of inflammation (SIRS)9or organ dysfunction(eg,SOFA,27,28Logistic Organ Dysfunction System30)(construct validity),and delineating their correlation with subquent outcomes(predictive validity).In addition,multivariable regression was ud to explore the perfor-mance of21bedside and laboratory criteria propod by the2001 task force.10
Full details are found in the accompanying article by Seymour et al.12In brief,electronic health record data of1.3million encoun-ters at12community and academic hospitals within the Univer-sity of Pittsburgh Medical Center health system in southwestern Pennsylvania were studied.There were148907patients with suspected infection,identified as tho who had body fluids sampled for culture and received antibiotics.Two outcomes—hospital mortality and mortality,ICU stay of3days or longer,or both—were ud to asss predictive validity both overall and across deciles of baline risk as determined by age,x,and comorbidity.For infected patients both inside and outside of the
IO2
Pa O2,partial pressure of oxygen.
risco
a Adapted from Vincent et al.27c Glasgow Coma Scale scores range from3-15;higher score indicates better neurological function.
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ICU,predictive validity was determined with 2metrics for each criterion:the area under the receiver operating characteristic curve (AUROC)and the change in outcomes comparing patients with a score of either 2points or more or fewer than 2points in the different scoring systems 9,27,30across deciles of baline risk.The criteria were also analyzed in 4external US and non-US data ts containing data from more than 700000patients (cared for in both community and tertiary care facilities)with both community-and hospital-acquired infection.
In ICU patients with suspected infection in the University of Pittsburgh Medical Center data t,discrimination for hospital mor-tality with SOFA (AUROC =0.74;95%CI,0.73-0.76)and the Logis-tic Organ Dysfunction System (AUROC =0.75;95%CI,0.72-0.76)was superior to that with SIRS (AUROC =0.64;95%CI,0.62-0.66).The predictive validity of a change in SOFA score of 2or greater was similar (AUROC =0.72;95%CI,0.70-0.73).For patients outside the ICU and with suspected infection,discrimination of hospital mortality with SOFA (AUROC =0.79;95%CI,0.78-0.80)or change in SOFA score (AUROC =0.79;95%CI,0.78-0.79)was similar to that with SIRS (AUROC =0.76;95%CI,0.75-0.77).
Becau SOFA is better known and simpler than the Logistic Organ Dysfunction System,the task force recommends using a change in baline of the total SOFA score of 2points or more to reprent organ dysfunction (Box 3).The baline SOFA score should be assumed to be zero unless the patient is known to have preexisting (acute or chronic)organ dysfunction before the ont of infection.Patients with a SOFA score of 2or more had an overall
托福词汇速记精典
mortality risk of approximately 10%in a general hospital popula-tion with presumed infection.12This is greater than the overall mor-tality rate of 8.1%for ST-gment elevation myocardial infarction,31a condition widely held to be life threatening by the community and by clinicians.Depending on a patient’s baline level of risk,a SOFA score of 2or greater identified a 2-to 25-fold incread risk of dying compared with patients with a SOFA score less than 2.12
As discusd later,the SOFA score is not intended to be ud as a tool for patient management but as a means to clinically char-acterize a ptic patient.Components of SOFA (such as creatinine or bilirubin level)require laboratory testing and thus may not promptly capture dysfunction in individual organ systems.Other elements,such as the cardiovascular score,can be affected by iat-rogenic interventions.However,SOFA has widespread familiarity within the critical care community and a well-validated relationship to mortality risk.It can be scored retrospectively,either manually or by automated systems,from clinical and laboratory measures often performed routinely as part of acute patient management.The task force noted that there are a number of novel biomarkers that can identify renal and hepatic dysfunction or coagulopathy earlier than the elements ud in SOFA,but the require broader validation before they can be incorporated into the clinical criteria describing psis.Future iterations of the psis definitions should include an updated SOFA score with more optimal variable lection,cutoff values,and weighting,or a superior scoring system.
Screening for Patients Likely to Have Sepsis
A parsimonious clinical model developed with multivariable logistic regression identified that any 2of 3clinical variables—Glasgow Coma Scale score of 13or less,systolic blood pressure of 100mm Hg or less,and respiratory rate 22/min or greater—offered predictive validity (AUROC =0.81;95%CI,0.80-0.82)similar to that of the full SOFA score outside the ICU.12This model was robust to multiple nsitivity analys including a more simple asssment of altered mentation (Glasgow Coma Scale score <15)and in the out-of-hospital,emergency department,and ward ttings within the external US and non-US data ts.
For patients with suspected infection within the ICU,the SOFA score had predictive validity (AUROC =0.74;95%CI,0.73-0.76)superior to that of this model (AUROC =0.66;95%CI,0.64-0.68),likely reflecting the modifying effects of interventions (eg,vaso-pressors,dative agents,mechanical ventilation).Addition of lac-tate measurement did not meaningfully improve predictive validity but may help identify patients at intermediate risk.
This new measure,termed qSOFA (for quick SOFA)and incor-porating altered mentation,systolic blood pressure of 100mm Hg or less,and respiratory rate of 22/min or greater,provides simple bedsid
mean taylor swifte criteria to identify adult patients with suspected infection who are likely to have poor outcomes (Box 4).Becau predictive validity was unchanged (P =.55),the task force cho to empha-size altered mentation becau it reprents any Glasgow Coma
加油的英文单词Connsus Definitions for Sepsis and Septic Shock Special Communication Clinical Review &Education
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