The Third International Consensus Definitions For Sepsis and Septic Shock (Sepsis-3)
The Third International Consensus Definitions For Sepsis and Septic Shock (Sepsis-3)
The Third International Consensus Definitions For Sepsis and Septic Shock (Sepsis-3)
CME Quiz at
PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and
jamanetworkcme.com and
epidemiology was convened by the Society of Critical Care Medicine and the European CME Questions page 816
Society of Intensive Care Medicine. Definitions and clinical criteria were generated through
meetings, Delphi processes, analysis of electronic health record databases, and voting,
followed by circulation to international professional societies, requesting peer review and
endorsement (by 31 societies listed in the Acknowledgment).
(Reprinted) 801
S
epsis, a syndrome of physiologic, pathologic, and bio-
chemical abnormalities induced by infection, is a major Box 1. SIRS (Systemic Inflammatory Response Syndrome)
public health concern, accounting for more than $20 bil- Two or more of:
lion (5.2%) of total US hospital costs in 2011.1 The reported inci- Temperature >38°C or <36°C
dence of sepsis is increasing,2,3 likely reflecting aging populations Heart rate >90/min
with more comorbidities, greater recognition,4 and, in some coun-
Respiratory rate >20/min or PaCO2 <32 mm Hg (4.3 kPa)
tries, reimbursement-favorable coding.5 Although the true inci-
White blood cell count >12 000/mm3 or <4000/mm3
dence is unknown, conservative estimates indicate that sepsis is a
or >10% immature bands
leading cause of mortality and critical illness worldwide.6,7 Further-
more, there is increasing awareness that patients who survive sep- From Bone et al.9
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jama.com (Reprinted) JAMA February 23, 2016 Volume 315, Number 8 803
Score
System 0 1 2 3 4
Respiration
PaO2/FIO2, mm Hg ≥400 (53.3) <400 (53.3) <300 (40) <200 (26.7) with <100 (13.3) with
(kPa) respiratory support respiratory support
Coagulation
Platelets, ×103/μL ≥150 <150 <100 <50 <20
Liver
Bilirubin, mg/dL <1.2 (20) 1.2-1.9 (20-32) 2.0-5.9 (33-101) 6.0-11.9 (102-204) >12.0 (204)
(μmol/L)
Cardiovascular MAP ≥70 mm Hg MAP <70 mm Hg Dopamine <5 or Dopamine 5.1-15 Dopamine >15 or
dobutamine (any dose)b or epinephrine ≤0.1 epinephrine >0.1
or norepinephrine ≤0.1b or norepinephrine >0.1b
Central nervous system
Glasgow Coma Scale 15 13-14 10-12 6-9 <6
scorec
Renal
Creatinine, mg/dL <1.2 (110) 1.2-1.9 (110-170) 2.0-3.4 (171-299) 3.5-4.9 (300-440) >5.0 (440)
(μmol/L)
Urine output, mL/d <500 <200
b
Abbreviations: FIO2, fraction of inspired oxygen; MAP, mean arterial pressure; Catecholamine doses are given as μg/kg/min for at least 1 hour.
PaO2, partial pressure of oxygen. c
Glasgow Coma Scale scores range from 3-15; higher score indicates better
a
Adapted from Vincent et al.27 neurological function.
tion is consistent with the view that cellular defects underlie physi-
A Need for Sepsis Definitions for the Public ologic and biochemical abnormalities within specific organ sys-
and for Health Care Practitioners tems. Under this terminology, “severe sepsis” becomes superfluous.
Sepsis should generally warrant greater levels of monitoring and in-
Despite its worldwide importance,6,7 public awareness of sepsis is tervention, including possible admission to critical care or high-
poor.29 Furthermore, the various manifestations of sepsis make di- dependency facilities.
agnosis difficult, even for experienced clinicians. Thus, the public
needs an understandable definition of sepsis, whereas health care Clinical Criteria to Identify Patients With Sepsis
practitioners require improved clinical prompts and diagnostic ap- The task force recognized that no current clinical measures reflect
proaches to facilitate earlier identification and an accurate quanti- the concept of a dysregulated host response. However, as noted
fication of the burden of sepsis. by the 2001 task force, many bedside examination findings and
routine laboratory test results are indicative of inflammation or
organ dysfunction.10 The task force therefore evaluated which
clinical criteria best identified infected patients most likely to
Results/Recommendations
have sepsis. This objective was achieved by interrogating large
Definition of Sepsis data sets of hospitalized patients with presumed infection,
Sepsis is defined as life-threatening organ dysfunction caused by a assessing agreement among existing scores of inflammation
dysregulated host response to infection (Box 3). This new defini- (SIRS) 9 or organ dysfunction (eg, SOFA, 27,28 Logistic Organ
tion emphasizes the primacy of the nonhomeostatic host response Dysfunction System30) (construct validity), and delineating their
to infection, the potential lethality that is considerably in excess of correlation with subsequent outcomes (predictive validity). In
a straightforward infection, and the need for urgent recognition. As addition, multivariable regression was used to explore the perfor-
described later, even a modest degree of organ dysfunction when mance of 21 bedside and laboratory criteria proposed by the 2001
infection is first suspected is associated with an in-hospital mortal- task force.10
ity in excess of 10%. Recognition of this condition thus merits a Full details are found in the accompanying article by Seymour
prompt and appropriate response. et al.12 In brief, electronic health record data of 1.3 million encoun-
Nonspecific SIRS criteria such as pyrexia or neutrophilia will con- ters at 12 community and academic hospitals within the Univer-
tinue to aid in the general diagnosis of infection. These findings sity of Pittsburgh Medical Center health system in southwestern
complement features of specific infections (eg, rash, lung consoli- Pennsylvania were studied. There were 148 907 patients with
dation, dysuria, peritonitis) that focus attention toward the likely ana- suspected infection, identified as those who had body fluids
tomical source and infecting organism. However, SIRS may simply sampled for culture and received antibiotics. Two outcomes—
reflect an appropriate host response that is frequently adaptive. Sep- hospital mortality and mortality, ICU stay of 3 days or longer, or
sis involves organ dysfunction, indicating a pathobiology more com- both—were used to assess predictive validity both overall and
plex than infection plus an accompanying inflammatory response across deciles of baseline risk as determined by age, sex, and
alone. The task force emphasis on life-threatening organ dysfunc- comorbidity. For infected patients both inside and outside of the
804 JAMA February 23, 2016 Volume 315, Number 8 (Reprinted) jama.com
Box 3. New Terms and Definitions Box 4. qSOFA (Quick SOFA) Criteria
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Scale score less than 15 and will reduce the measurement burden. combinations and different lactate thresholds. The first database
Although qSOFA is less robust than a SOFA score of 2 or greater in interrogated was the Surviving Sepsis Campaign’s international
the ICU, it does not require laboratory tests and can be assessed multicenter registry of 28 150 infected patients with at least 2 SIRS
quickly and repeatedly. The task force suggests that qSOFA criteria criteria and at least 1 organ dysfunction criterion. Hypotension was
be used to prompt clinicians to further investigate for organ dys- defined as a mean arterial pressure less than 65 mm Hg, the only
function, to initiate or escalate therapy as appropriate, and to con- available cutoff. A total of 18 840 patients with vasopressor
sider referral to critical care or increase the frequency of monitor- therapy, hypotension, or hyperlactatemia (>2 mmol/L [18 mg/dL])
ing, if such actions have not already been undertaken. The task after volume resuscitation were identified. Patients with fluid-
force considered that positive qSOFA criteria should also prompt resistant hypotension requiring vasopressors and with hyperlacta-
consideration of possible infection in patients not previously recog- temia were used as the referent group for comparing between-
nized as infected. group differences in the risk-adjusted odds ratio for mortality. Risk
adjustment was performed with a generalized estimating equation
Definition of Septic Shock population-averaged logistic regression model with exchangeable
Septic shock is defined as a subset of sepsis in which underlying cir- correlation structure.
culatory and cellular metabolism abnormalities are profound enough Risk-adjusted hospital mortality was significantly higher
to substantially increase mortality (Box 3). The 2001 task force defi- (P < .001 compared with the referent group) in patients with fluid-
nitions described septic shock as “a state of acute circulatory resistant hypotension requiring vasopressors and hyperlactatemia
failure.”10 The task force favored a broader view to differentiate sep- (42.3% and 49.7% at thresholds for serum lactate level of
tic shock from cardiovascular dysfunction alone and to recognize the >2 mmol/L [18 mg/dL] or >4 mmol/L [36 mg/dL], respectively)
importance of cellular abnormalities (Box 3). There was unanimous compared with either hyperlactatemia alone (25.7% and 29.9%
agreement that septic shock should reflect a more severe illness with mortality for those with serum lactate level of >2 mmol/L
a much higher likelihood of death than sepsis alone. [18 mg/dL] and >4 mmol/L [36 mg/dL], respectively) or with fluid-
resistant hypotension requiring vasopressors but with lactate level
Clinical Criteria to Identify Septic Shock of 2 mmol/L (18 mg/dL) or less (30.1%).
Further details are provided in the accompanying article by With the same 3 variables and similar categorization, the unad-
Shankar-Hari et al.13 First, a systematic review assessed how cur- justed mortality in infected patients within 2 unrelated large elec-
rent definitions were operationalized. This informed a Delphi pro- tronic health record data sets (University of Pittsburgh Medical
cess conducted among the task force members to determine the Center [12 hospitals; 2010-2012; n = 5984] and Kaiser Permanente
updated septic shock definition and clinical criteria. This process Northern California [20 hospitals; 2009-2013; n = 54 135]) showed
was iterative and informed by interrogation of databases, as sum- reproducible results. The combination of hypotension, vasopressor
marized below. use, and lactate level greater than 2 mmol/L (18 mg/dL) identified
The Delphi process assessed agreements on descriptions of patients with mortality rates of 54% at University of Pittsburgh
terms such as “hypotension,” “need for vasopressor therapy,” “raised Medical Center (n = 315) and 35% at Kaiser Permanente Northern
lactate,” and “adequate fluid resuscitation” for inclusion within the California (n = 8051). These rates were higher than the mortality
new clinical criteria. The majority (n = 14/17; 82.4%) of task force rates of 25.2% (n = 147) and 18.8% (n = 3094) in patients with
members voting on this agreed that hypotension should be de- hypotension alone, 17.9% (n = 1978) and 6.8% (n = 30 209) in
noted as a mean arterial pressure less than 65 mm Hg according to patients with lactate level greater than 2 mmol/L (18 mg/dL) alone,
the pragmatic decision that this was most often recorded in data sets and 20% (n = 5984) and 8% (n = 54 135) in patients with sepsis at
derived from patients with sepsis. Systolic blood pressure was used University of Pittsburgh Medical Center and Kaiser Permanente
as a qSOFA criterion because it was most widely recorded in the elec- Northern California, respectively.
tronic health record data sets. The task force recognized that serum lactate measurements are
A majority (11/17; 64.7%) of the task force agreed, whereas 2 commonly, but not universally, available, especially in developing
(11.8%) disagreed, that an elevated lactate level is reflective of cel- countries. Nonetheless, clinical criteria for septic shock were devel-
lular dysfunction in sepsis, albeit recognizing that multiple factors, oped with hypotension and hyperlactatemia rather than either alone
such as insufficient tissue oxygen delivery, impaired aerobic respi- because the combination encompasses both cellular dysfunction and
ration, accelerated aerobic glycolysis, and reduced hepatic clear- cardiovascular compromise and is associated with a significantly
ance, also contribute.32 Hyperlactatemia is, however, a reasonable higher risk-adjusted mortality. This proposal was approved by a ma-
marker of illness severity, with higher levels predictive of higher jority (13/18; 72.2%) of voting members13 but warrants revisiting. The
mortality.33 Criteria for “adequate fluid resuscitation” or “need for Controversies and Limitations section below provides further dis-
vasopressor therapy” could not be explicitly specified because cussion about the inclusion of both parameters and options for when
these are highly user dependent, relying on variable monitoring lactate level cannot be measured.
modalities and hemodynamic targets for treatment. 34 Other
aspects of management, such as sedation and volume status
assessment, are also potential confounders in the hypotension-
Recommendations for ICD Coding
vasopressor relationship.
and for Lay Definitions
By Delphi consensus process, 3 variables were identified
(hypotension, elevated lactate level, and a sustained need for vaso- In accordance with the importance of accurately applying diagnos-
pressor therapy) to test in cohort studies, exploring alternative tic codes, Table 2 details how the new sepsis and septic shock clini-
806 JAMA February 23, 2016 Volume 315, Number 8 (Reprinted) jama.com
cal criteria correlate with ICD-9-CM and ICD-10 codes. The task
Table 2. Terminology and International Classification of Diseases Coding
force also endorsed the recently published lay definition that
Current Guidelines
“sepsis is a life-threatening condition that arises when the body’s and Terminology Sepsis Septic Shock
response to infection injures its own tissues,” which is consistent 1991 and 2001 Severe sepsis Septic shock13
with the newly proposed definitions described above.35 To trans- consensus Sepsis-induced
terminology9,10 hypoperfusion
mit the importance of sepsis to the public at large, the task force
2015 Definition Sepsis is Septic shock is a subset of
emphasizes that sepsis may portend death, especially if not recog- life-threatening organ sepsis in which underlying
nized early and treated promptly. Indeed, despite advances that dysfunction caused by a circulatory and
dysregulated host cellular/metabolic
include vaccines, antibiotics, and acute care, sepsis remains the pri- response to infection abnormalities are profound
mary cause of death from infection. Widespread educational cam- enough to substantially
increase mortality
paigns are recommended to better inform the public about this 2015 Clinical Suspected or Sepsisa
lethal condition. criteria documented infection and
and vasopressor therapy needed to
an acute increase of ≥2 elevate MAP ≥65 mm Hg
SOFA points (a proxy and
for organ dysfunction) lactate >2 mmol/L (18 mg/dL)
Controversies and Limitations despite adequate fluid
resuscitation13
There are inherent challenges in defining sepsis and septic shock. Recommended
primary ICD
First and foremost, sepsis is a broad term applied to an incom- codesa
pletely understood process. There are, as yet, no simple and unam- ICD-9 995.92 785.52
biguous clinical criteria or biological, imaging, or laboratory features ICD-10a R65.20 R65.21
that uniquely identify a septic patient. The task force recognized Framework for Identify suspected infection by using concomitant orders
the impossibility of trying to achieve total consensus on all points. implementation for blood cultures and antibiotics (oral or parenteral) in a
for coding and specified periodb
Pragmatic compromises were necessary, so emphasis was placed research Within specified period around suspected infectionc:
on generalizability and the use of readily measurable identifiers 1. Identify sepsis by using a clinical criterion for
life-threatening organ dysfunction
that could best capture the current conceptualization of underlying 2. Assess for shock criteria, using administration of
mechanisms. The detailed, data-guided deliberations of the task vasopressors, MAP <65 mm Hg, and lactate >2 mmol/L
(18 mg/dL)d
force during an 18-month period and the peer review provided by
Abbreviations: ICD, International Classification of Diseases; MAP, mean arterial
bodies approached for endorsement highlighted multiple areas for pressure; SOFA, Sequential [Sepsis-related] Organ Failure Assessment.27
discussion. It is useful to identify these issues and provide justifica- a
Included training codes.
tions for the final positions adopted. b
Suspected infection could be defined as the concomitant administration of
The new definition of sepsis reflects an up-to-date view of patho- oral or parenteral antibiotics and sampling of body fluid cultures (blood, urine,
biology, particularly in regard to what distinguishes sepsis from un- cerebrospinal fluid, peritoneal, etc). For example, if the culture is obtained, the
complicated infection. The task force also offers easily measurable antibiotic is required to be administered within 72 hours, whereas if the
antibiotic is first, the culture is required within 24 hours.12
clinical criteria that capture the essence of sepsis yet can be trans- c
Considers a period as great as 48 hours before and up to 24 hours after onset
lated and recorded objectively (Figure). Although these criteria of infection, although sensitivity analyses have tested windows as short as
cannot be all-encompassing, they are simple to use and offer con- 3 hours before and 3 hours after onset of infection.12
sistency of terminology to clinical practitioners, researchers, admin- d
With the specified period around suspected infection, assess for shock criteria,
istrators, and funders. The physiologic and biochemical tests re- using any vasopressor initiation (eg, dopamine, norepinephrine, epinephrine,
vasopressin, phenylephrine), any lactate level >2 mmol/L (18 mg/dL), and
quired to score SOFA are often included in routine patient care, and
mean arterial pressure <65 mm Hg. These criteria require adequate fluid
scoring can be performed retrospectively. resuscitation as defined by the Surviving Sepsis Campaign guidelines.4
The initial, retrospective analysis indicated that qSOFA could
be a useful clinical tool, especially to physicians and other practi- scored at the bedside without the need for blood tests, and it is
tioners working outside the ICU (and perhaps even outside the hoped that it will facilitate prompt identification of an infection that
hospital, given that qSOFA relies only on clinical examination find- poses a greater threat to life. If appropriate laboratory tests have
ings), to promptly identify infected patients likely to fare poorly. not already been undertaken, this may prompt testing to identify
However, because most of the data were extracted from extracted biochemical organ dysfunction. These data will primarily aid patient
US databases, the task force strongly encourages prospective vali- management but will also enable subsequent SOFA scoring. The
dation in multiple US and non-US health care settings to confirm its task force wishes to stress that SIRS criteria may still remain useful
robustness and potential for incorporation into future iterations of for the identification of infection.
the definitions. This simple bedside score may be particularly rel- Some have argued that lactate measurement should be man-
evant in resource-poor settings in which laboratory data are not dated as an important biochemical identifier of sepsis in an infected
readily available, and when the literature about sepsis epidemiol- patient. Because lactate measurement offered no meaningful
ogy is sparse. change in the predictive validity beyond 2 or more qSOFA criteria in
Neither qSOFA nor SOFA is intended to be a stand-alone defi- the identification of patients likely to be septic, the task force could
nition of sepsis. It is crucial, however, that failure to meet 2 or more not justify the added complexity and cost of lactate measurement
qSOFA or SOFA criteria should not lead to a deferral of investigation alongside these simple bedside criteria. The task force recommen-
or treatment of infection or to a delay in any other aspect of care dations should not, however, constrain the monitoring of lactate as
deemed necessary by the practitioners. qSOFA can be rapidly a guide to therapeutic response or as an indicator of illness severity.
jama.com (Reprinted) JAMA February 23, 2016 Volume 315, Number 8 807
Figure. Operationalization of Clinical Criteria Identifying Patients With Sepsis and Septic Shock
Sepsis
B SOFA Variables
PaO2/FiO2 ratio
Despite adequate fluid resuscitation, Glasgow Coma Scale score
1. vasopressors required to maintain Mean arterial pressure
No
MAP ≥65 mm Hg
AND Administration of vasopressors
2. serum lactate level >2 mmol/L? with type and dose rate of infusion
Serum creatinine or urine output
Yes Bilirubin
Septic shock Platelet count
The baseline Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score should be assumed to be zero unless the patient is known to have preexisting
(acute or chronic) organ dysfunction before the onset of infection. qSOFA indicates quick SOFA; MAP, mean arterial pressure.
808 JAMA February 23, 2016 Volume 315, Number 8 (Reprinted) jama.com
miology is assessed and reported, operationalization will neces- enhanced collection of data will fuel their continued reevaluation
sarily involve proxies such as antibiotic commencement or a clini- and revision.
cally determined probability of infection. Future epidemiology
studies should consider reporting the proportion of microbiology-
positive sepsis.
Conclusions
Greater clarity and consistency will also facilitate research and
more accurate coding. Changes to ICD coding may take several years These updated definitions and clinical criteria should clarify long-
to enact, so the recommendations provided in Table 2 demon- used descriptors and facilitate earlier recognition and more timely
strate how the new definitions can be applied in the interim within management of patients with sepsis or at risk of developing it. This
the current ICD system. process, however, remains a work in progress. As is done with soft-
The debate and discussion that this work will inevitably ware and other coding updates, the task force recommends that the
generate are encouraged. Aspects of the new definitions do new definition be designated Sepsis-3, with the 1991 and 2001 it-
indeed rely on expert opinion; further understanding of the biol- erations being recognized as Sepsis-1 and Sepsis-2, respectively, to
ogy of sepsis, the availability of new diagnostic approaches, and emphasize the need for future iterations.
ARTICLE INFORMATION Acquisition, analysis, or interpretation of data: All his time spent in these roles. Dr Hotchkiss reports
Author Affiliations: Bloomsbury Institute of authors. consulting on sepsis for GlaxoSmithKline, Merck,
Intensive Care Medicine, University College Drafting of the manuscript: Singer, Deutschman, and Bristol-Meyers Squibb and reports that his
London, London, United Kingdom (Singer); Seymour, Shankar-Hari, Angus. institution received grant support from Bristol-
Hofstra–Northwell School of Medicine, Feinstein Critical revision of the manuscript for important Meyers Squibb and GlaxoSmithKline, as well as the
Institute for Medical Research, New Hyde Park, intellectual content: All authors. NIH, for research on sepsis. Dr Marshall reports
New York (Deutschman); Department of Critical Statistical analysis: Shankar-Hari, Seymour. serving on the data and safety monitoring board
Care and Emergency Medicine, University of Obtained funding: Deutschman, Chiche, (DSMB) of AKPA Pharma and Spectral Medical
Pittsburgh School of Medicine, Pittsburgh, Coopersmith. Steering Committee and receiving payment for
Pennsylvania (Seymour); Department of Critical Administrative, technical, or material support: speaking from Toray Ltd and Uni-Labs. Dr Martin
Care Medicine, Guy’s and St Thomas’ NHS Singer, Deutschman, Chiche, Coopersmith, reports serving on the board for SCCM and Project
Foundation Trust, London, United Kingdom Levy, Angus. Help, serving on the DSMB for Cumberland
(Shankar-Hari); Department of Critical Care Study supervision: Singer, Deutschman. Pharmaceuticals and Vanderbilt University, serving
Medicine, University of Versailles, France (Annane); Drs Singer and Deutschman are joint first authors. on the medical advisory board for Grifols and
Center for Sepsis Control and Care, University Conflict of Interest Disclosures: All authors have Pulsion Medical Systems, and grants to his
Hospital, Jena, Germany (Bauer); Australian and completed and submitted the ICMJE Form for institution from NIH, the Food and Drug
New Zealand Intensive Care Research Centre, Disclosure of Potential Conflicts of Interest. Administration, Abbott, and Baxter. Dr Opal reports
School of Public Health and Preventive Medicine, Dr Singer reports serving on the advisory boards of grants from GlaxoSmithKline, Atoxbio, Asahi-Kasei,
Monash University, Melbourne, and Austin Hospital, InflaRx, Bayer, Biotest, and Merck and that his Ferring, Cardeas, and Arsanis outside the submitted
Melbourne, Victoria, Australia (Bellomo); Vanderbilt institution has received grants from the European work; personal fees from Arsanis, Aridis, Bioaegis,
Institute for Clinical and Translational Research, Commission, UK National Institute of Health Cyon, and Battelle; and serving on the DSMB for
Vanderbilt University, Nashville, Tennessee Research, Immunexpress, DSTL, and Wellcome Achaogen, Spectral Diagnostics, and Paratek. No
(Bernard); Réanimation Médicale-Hôpital Cochin, Trust. Dr Deutschman reports holding patents on other disclosures were reported.
Descartes University, Cochin Institute, Paris, France materials not related to this work and receiving Funding/Support: This work was supported in part
(Chiche); Critical Care Center, Emory University travel/accommodations and related expenses for by a grant from the Society of Critical Care Medicine
School of Medicine, Atlanta, Georgia participation in meetings paid by the Centers for (SCCM) and the European Society of Intensive Care
(Coopersmith); Washington University School of Disease Control and Prevention, World Federation Medicine (ESICM).
Medicine, St Louis, Missouri (Hotchkiss); Infectious of Societies of Intensive and Critical Care, Role of the Funder/Sponsor: These funding bodies
Disease Section, Division of Pulmonary and Critical Pennsylvania Assembly of Critical Care Medicine/PA appointed cochairs but otherwise had no role in the
Care Medicine, Brown University School of Chapter, Society of Critical Care Medicine design and conduct of the work; the collection,
Medicine, Providence, Rhode Island (Levy, Opal); (SCCM)/Penn State–Hershey Medical Center, management, analysis, and interpretation of the
Department of Surgery, University of Toronto, Society of Critical Care Medicine, Northern Ireland data; preparation of the manuscript; or decision to
Toronto, Ontario, Canada (Marshall); Emory Society of Critical Care Medicine, International submit the manuscript for publication. As other
University School of Medicine and Grady Memorial Sepsis Forum, Department of Anesthesiology, national and international societies, they were
Hospital, Atlanta, Georgia (Martin); Trauma, Stanford University, Acute Dialysis Quality Initiative, asked for comment and endorsement.
Emergency & Critical Care Program, Sunnybrook and European Society of Intensive Care Medicine
Health Sciences Centre, Toronto, Ontario, Canada (ESICM). Dr Seymour reports receiving personal Disclaimer: Dr Angus, JAMA Associate Editor, had
(Rubenfeld); Interdepartmental Division of Critical fees from Beckman Coulter and a National no role in the evaluation of or decision to publish
Care, University of Toronto (Rubenfeld); Institutes of Health (NIH) grant awarded to his this article.
Department of Infectious Diseases, Academisch institution. Dr Bauer reports support for travel to Endorsing Societies: Academy of Medical Royal
Medisch Centrum, Amsterdam, the Netherlands meetings for the study from ESICM, payment for Colleges (UK); American Association of Critical Care
(van der Poll); Department of Intensive Care, speaking from CSL Behring, grants to his institution Nurses; American Thoracic Society (endorsed
Erasme University Hospital, Brussels, Belgium from Jena University Hospital, and patents held by August 25, 2015); Australian–New Zealand
(Vincent); Department of Critical Care Medicine, Jena University Hospital. Dr Bernard reports grants Intensive Care Society (ANZICS); Asia Pacific
University of Pittsburgh and UPMC Health System, from AstraZeneca for activities outside the Association of Critical Care Medicine; Brasilian
Pittsburgh, Pennsylvania (Angus); Associate Editor, submitted work. Dr Chiche reports consulting for Society of Critical Care; Central American and
JAMA (Angus). Nestlé and Abbott and honoraria for speaking from Caribbean Intensive Therapy Consortium; Chinese
Author Contributions: Drs Singer and Deutschman GE Healthcare and Nestlé. Dr Coopersmith reports Society of Critical Care Medicine; Chinese Society of
had full access to all of the data in the study and receiving grants from the NIH for work not related Critical Care Medicine–China Medical Association;
take responsibility for the integrity of the data and to this article. Dr Coopersmith also reports bring Critical Care Society of South Africa; Emirates
the accuracy of the data analysis. president-elect and president of SCCM when the Intensive Care Society; European Respiratory
Study concept and design: All authors. task force was meeting and the article was being Society; European Resuscitation Council; European
drafted. A stipend was paid to Emory University for Society of Clinical Microbiology and Infectious
jama.com (Reprinted) JAMA February 23, 2016 Volume 315, Number 8 809
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PhD, University of Michigan; Vincent Liu, MD, MSc, Assessment of clinical criteria for sepsis. JAMA. doi: Working Group on “Sepsis-Related Problems” of the
Kaiser Permanente Northern California; Thomas 10.1001/jama.2016.0288. European Society of Intensive Care Medicine. Use
Rea, MD, MPH, University of Washington; and Gary of the SOFA score to assess the incidence of organ
Phillips, MAS, Ohio State University; for their 13. Shankar-Hari M, Phillips G, Levy ML, et al
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