Clinical Review & Education

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Special Communication | CARING FOR THE CRITICALLY ILL PATIENT

The Third International Consensus 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

BELISARIO
Editorial page 757
IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001.
Author Video Interview,
Considerable advances have since been made into the pathobiology (changes in Author Audio Interview, and
organ function, morphology, cell biology, biochemistry, immunology, and JAMA Report Video at
circulation), management, and epidemiology of sepsis, suggesting the need for jama.com
reexamination.
Related articles pages 762
and 775
OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock.
CME Quiz at
jamanetworkcme.com and
PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical
CME Questions page 816
trials, and epidemiology was convened by the Society of Critical Care Medicine
and the European 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).

KEY FINDINGS FROM EVIDENCE SYNTHESIS Limitations of previous definitions

included an excessive focus on inflammation, the misleading model that sepsis
follows a continuum through severe sepsis to shock, and inadequate specificity and
sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple
definitions and terminologies are currently in use for sepsis, septic shock, and organ
dysfunction, leading to discrepancies in reported incidence and observed mortality.
The task force concluded the term severe sepsis was redundant.

RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction

caused by a dysregulated host response to infection. For clinical
operationalization, organ dysfunction can be represented by an increase in the
JAMA. 2016;315(8):801-810.
Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or doi:10.1001/jama.2016.0287
more, which is associated with an in-hospital mortality greater than 10%. Septic shock
should be defined as a subset of sepsis in which particularly profound circulatory,
cellular, and metabolic abnormalities are associated with
a greater risk of mortality than with sepsis alone. Patients with septic shock can be
clinically identified by a vasopressor requirement to maintain a mean arterial pressure
of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18
mg/dL) in the absence of hypovolemia. This combination is associated with hospital
mortality rates greater than 40%.
In out-of-hospital, emergency department, or general hospital ward settings, adult
patients with suspected infection can be rapidly identified as being more likely to have
poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria
that together constitute a new bedside clinical score termed quickSOFA (qSOFA):
respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of
100 mm Hg or less.

CONCLUSIONS AND RELEVANCE These updated definitions and clinical criteria should
replace previous definitions, offer greater consistency for epidemiologic studies and
clinical trials, and facilitate earlier recognition and more timely management of patients
with sepsis or at risk of developing sepsis.

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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 Research,
269-01 76th Ave, New Hyde Park, NY 11040 (cdeutschman@nshs.edu).

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S
epsis, a syndrome of physiologic, pathologic, and performed in multiple large electronic health record
bio- chemical abnormalities induced by infection, is a data- bases that also addressed the absence
major public health concern, accounting for more than (missingness) of individual elements of different organ
$20 bil- dysfunction scores and the question of generalizability
1
lion (5.2%) of total US hospital costs in 2011. The reported (ecologic validity).12 A systematic literature
2,3
inci- dence of sepsis is increasing, likely reflecting aging
populations with more comorbidities, greater recognition,4
and, in some coun- tries, reimbursement-favorable coding.5
Although the true inci- dence is unknown, conservative
estimates indicate that sepsis is a leading cause of mortality
6,7
and critical illness worldwide. Further- more, there is
increasing awareness that patients who survive sep- sis often
have long-term physical, psychological, and cognitive dis-
abilities with significant health care and social implications.8
A 1991 consensus conference9 developed initial definitions
that focused on the then-prevailing view that sepsis resulted
from a host’s systemic inflammatory response syndrome
(SIRS) to infection (Box 1). Sepsis complicated by organ
dysfunction was termed severe sepsis, which could progress
to septic shock, defined as “sepsis-induced hypotension
persisting despite adequate fluid resuscitation.” A 2001 task
force, recognizing limi- tations with these definitions,
expanded the list of diagnostic cri- teria but did not offer
alternatives because of the lack of support- ing evidence.10 In
effect, the definitions of sepsis, septic shock, and organ
dysfunction have remained largely unchanged for more
than 2 decades.

The Process of Developing New Definitions

Recognizing the need to reexamine the current definitions,11
the European Society of Intensive Care Medicine and the
Society of Critical Care Medicine convened a task force of 19
critical care, infectious disease, 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 selected
members according to their scientific expertise in sepsis
epidemiology, clinical trials, and basic or translational research.
The group engaged in iterative discussions via 4 face-to-
face meetings between January 2014 and January 2015,
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 databases and patient cohorts.
An expert consensus process, based on a current
under- standing of sepsis-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 discussed below.
The agreement between potential clinical criteria (construct
validity) and the ability of the criteria to predict outcomes
typical of sepsis, such as need for intensive care unit (ICU)
admission or death (predictive validity, a form of criterion
validity), were then tested. These explorations were
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 Clinical Review & Education Special Communication Consensus Definitions for Sepsis and Septic
Shock
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Box 1. SIRS (Systemic Inflammatory Response Syndrome)

Two or more of:

Temperature >38°C or <36°C
Heart rate >90/min
Respiratory rate >20/min or PaCO2 <32 mm Hg (4.3 kPa)
White blood cell count >12 000/mm3 or
<4000/mm3 or >10% immature bands

From Bone et al.9

review and Delphi consensus methods were also used for the
definition and clinical criteria describing septic shock.13
When compiled, the task force recommendations with sup-
porting evidence, including original research, were circulated to
major international societies and other relevant bodies for peer
review and endorsement (31 endorsing societies are listed at the
end of this article).

Issues Addressed by the Task Force

The task force sought to differentiate sepsis from uncomplicated
infection and to update definitions of sepsis and septic shock to be
consistent with improved understanding of the pathobiology. A
definition is the description of an illness concept; thus, a definition
of sepsis should describe what sepsis “is.” This chosen approach
allowed discussion of biological concepts that are currently incom-
pletely understood, such as genetic influences and cellular abnor-
malities. The sepsis 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 sepsis is a syndrome without, at
present, a validated criterion standard diagnostic test. There is
currently no process to operationalize the definitions of sepsis
and septic shock, a key deficit that has led to major variations
in reported incidence and mortality rates (see 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, these clinical criteria should identify all the elements
of sepsis (infection, host response, 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 these criteria with available large clinical data sets and,
ultimately, prospectively. In addition, clinical criteria should be
available to provide practitioners in out-of-hospital, emergency
department, and hospital ward settings with the capacity to
better identify patients with suspected infection likely to
progress to a life- threatening state. Such early recognition is
particularly important because prompt management of septic
patients may improve outcomes.4
In addition, to provide a more consistent and reproducible pic-
ture of sepsis incidence and outcomes, the task force sought to in-
tegrate the biology and clinical identification of sepsis with its epi-
demiology and coding.

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Identified Challenges and Opportunities Box 2. Key Concepts of Sepsis

• Sepsis is the primary cause of death from infection,

Assessing the Validity of Definitions threatening
especially ifresponse. SIRSand
not recognized criteria
treatedare present
promptly. Its in many hospitalized
When There Is No Gold Standard patients, including
recognition mandates those
urgentwho never develop infection and never
attention.
25
Sepsis is not a specific illness but rather a syndrome incur
• adverse
Sepsisoutcomes (poor
is a syndrome dis-bycriminant
shaped validity).
pathogen factors and In addition, 1
encompassing a still-uncertain pathobiology. At present, it can in 8host
patients
factorsadmitted to criti-
(eg, sex, race and other genetic determinants,
be identified by a constellation of clinical signs and symptoms age, comorbidities, environment) with characteristics that
in a patient with sus- pected infection. Because no gold evolve over time. What differentiates sepsis from infection is
an aberrant or dysregulated host response and the presence of
standard diagnostic test exists, the task force sought definitions
organ dysfunction.
and supporting clinical criteria that were clear and fulfilled
• Sepsis-induced organ dysfunction may be occult; therefore,
multiple domains of usefulness and validity.
its presence should be considered in any patient presenting
with infection. Conversely, unrecognized infection may be the
Improved Understanding of Sepsis Pathobiology cause of new-onset organ dysfunction. Any unexplained organ
Sepsis is a multifaceted host response to an infecting dysfunction should thus raise the possibility of underlying
pathogen that may be significantly amplified by endogenous infection.
14,15
factors. The original conceptualization of sepsis as infection • The clinical and biological phenotype of sepsis can be
with at least 2 of the 4 SIRS criteria focused solely on modified by preexisting acute illness, long-standing
inflammatory excess. How- ever, the validity of SIRS as a comorbidities, medication, and interventions.
descriptor of sepsis pathobiology has been challenged. Sepsis • Specific infections may result in local organ
is now recognized to involve early activa- tion of both pro- dysfunction without generating a dysregulated systemic host
16
and anti-inflammatory responses, along with major
modifications in nonimmunologic pathways such as cardio-
vascular, neuronal, autonomic, hormonal, bioenergetic, metabolic,
and coagulation,14,17,18 all of which have prognostic
significance. Organ dysfunction, even when severe, is not
associated with sub- stantial cell death.19
The broader perspective also emphasizes the significant
bio- logical and clinical heterogeneity in affected
individuals,20 with age, underlying comorbidities, concurrent
injuries (including sur- gery) and medications, and source of
infection adding further complexity.21 This diversity cannot be
appropriately recapitulated in either animal models or
computer simulations.14 With further validation, multichannel
molecular signatures (eg, transcriptomic, metabolomic,
proteomic) will likely lead to better characterization of specific
population subsets.22,23 Such signatures may also help to
differentiate sepsis from noninfectious insults such as trauma
or pancreatitis, in which a similar biological and clinical host
response may be triggered by endogenous factors.24 Key
concepts of sepsis describing its protean nature are
highlighted in Box 2.

Variable Definitions
A better understanding of the underlying pathobiology has
been accompanied by the recognition that many existing
terms (eg, sep- sis, severe sepsis) are used interchangeably,
whereas others are redundant (eg, sepsis syndrome) or overly
narrow (eg, septicemia). Inconsistent strategies in selecting
International Classification of Diseases, Ninth Revision (ICD-
9), and ICD-10 codes have com- pounded the problem.

Sepsis
The current use of 2 or more SIRS criteria (Box 1) to identify
sepsis was unanimously considered by the task force to be
unhelpful. Changes in white blood cell count, temperature,
and heart rate reflect inflammation, the host response to
“danger” in the form of infection or other insults. The SIRS
criteria do not necessarily indi- cate a dysregulated, life-
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 Clinical Review & Education Special Communication Consensus Definitions for Sepsis and Septic
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cutoffs for systolic or mean blood pressure  diverse levels of
hyperlactatemia  vasopressor use  concurrent new organ
dysfunction  defined fluid resuscita- tion volume/targets), the
data source and coding methods, and enrollment dates.

cal care units in Australia and New Zealand with

infection and new organ failure did not have the
requisite minimum of 2 SIRS criteria to fulfill the
definition of sepsis (poor concurrent validity) yet had
protracted courses with significant morbidity and
mortality.26 Discriminant validity and convergent
validity constitute the 2 domains of construct
validity; the SIRS criteria thus perform poorly on
both counts.

Organ Dysfunction or Failure

Severity of organ dysfunction has been assessed with
various scor- ing systems that quantify abnormalities
according to clinical find- ings, laboratory data, or
therapeutic interventions. Differences in these
scoring systems have also led to inconsistency in
reporting. The predominant score in current use is
the Sequential Organ Fail- ure Assessment (SOFA)
(originally the Sepsis-related Organ Failure
Assessment27) (Table 1).28 A higher SOFA score is
associated with an increased probability of
mortality.28 The score grades abnormal- ity by organ
system and accounts for clinical interventions. How-
ever, laboratory variables, namely, PaO2, platelet
count, creatinine level, and bilirubin level, are
needed for full computation. Further- more, selection
of variables and cutoff values were developed by
consensus, 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 use.

Septic Shock
Multiple definitions for septic shock are currently in
use. Further details are provided in an accompanying
article by Shankar-Hari et al.13 A systematic review
of the operationalization of current definitions
highlights significant heterogeneity in reported
mortality. This heterogeneity resulted from
differences in the clinical variables chosen (varying
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Table 1. Sequential [Sepsis-Related] Organ Failure Assessment Score a
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 MAP <70 mm Dopamine <5 or Dopamine 5.1-15 Dopamine >15
Hg Hg or dobutamine (any dose)b or epinephrine ≤0.1 epinephrine >0.1
or norepinephrine ≤0.1 or norepinephrine >0.1b
b

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
Abbreviations: FIO2, fraction of inspired oxygen; MAP, mean arterial b
Catecholamine doses are given as μg/kg/min for at least 1 hour.
pressure; PaO2, partial pressure of oxygen. c
Glasgow Coma Scale scores range from 3-15; higher score indicates
a
Adapted from Vincent et al.27 better neurological function.

infection plus an accompanying inflammatory response

alone. The task force emphasis on life-threatening organ
A Need for Sepsis Definitions for the
dysfunc-
Public and for Health Care Practitioners
Despite its worldwide importance,6,7 public awareness of
29
sepsis is poor. Furthermore, the various manifestations of
sepsis make di- agnosis difficult, even for experienced
clinicians. Thus, the public needs an understandable definition
of sepsis, 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 sepsis.

Results/Recommendations
Definition of Sepsis
Sepsis is defined as life-threatening organ dysfunction caused
by a dysregulated host response to infection (Box 3). This
new defini- tion emphasizes the primacy of the
nonhomeostatic host response 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 of 10%. Recognition of this condition
thus merits a prompt and appropriate response.
Nonspecific SIRS criteria such as pyrexia or neutrophilia will
con- tinue to aid in the general diagnosis of infection.
These findings complement features of specific infections
(eg, rash, lung consoli- dation, dysuria, peritonitis) that focus
attention toward the likely ana- tomical source and infecting
organism. However, SIRS may simply reflect an appropriate
host response that is frequently adaptive. Sep- sis involves organ
dysfunction, indicating a pathobiology more com- plex than
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 Clinical Review & Education Special Communication Consensus Definitions for Sepsis and Septic
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tion is consistent with the view that cellular defects underlie physi-
ologic and biochemical abnormalities within specific organ sys-
tems. Under this terminology, “severe sepsis” 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 response. However, as noted
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
have sepsis. This objective was achieved by interrogating large
data sets of hospitalized patients with presumed infection,
assessing agreement among existing scores of inflammation
(SIRS) 9 or organ dysfunction (eg, SOFA,27,28 Logistic Organ
30
Dysfunction System ) (construct validity), and delineating their
correlation with subsequent outcomes (predictive validity). In
addition, multivariable regression was used to explore the perfor-
mance of 21 bedside and laboratory criteria proposed by the 2001
task force.10
Full details are found in the accompanying article by Seymour
et al.12 In brief, electronic health record data of 1.3 million encoun-
ters at 12 community and academic hospitals within the Univer-
sity of Pittsburgh Medical Center health system in southwestern
Pennsylvania were studied. There were 148 907 patients with
suspected infection, identified as those who had body fluids
sampled for culture and received antibiotics. Two outcomes—
hospital mortality and mortality, ICU stay of 3 days or longer, or
both—were used to assess predictive validity both overall and
across deciles of baseline risk as determined by age, sex,
and comorbidity. For infected patients both inside and outside of
the

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Box 3. New Terms and Definitions Box 4. qSOFA (Quick SOFA) Criteria
• Sepsis is defined as life-threatening organ dysfunction Respiratory rate Š22/min
caused by a dysregulated host response to infection.
Altered mentation
• Organ dysfunction can be identified as an acute
Systolic blood pressure Š100 mm Hg
change in total SOFA score Š2 points consequent to the
infection.
• The baseline SOFA score can be assumed to be zero in zero unless the patient is known to have preexisting (acute or chronic)
patients not known to have preexisting organ dysfunction. organ dysfunction before the onset of infection. Patients with a SOFA
• A SOFA score Š2 reflects an overall mortality score of 2 or more had an overall
risk of approximately 10% in a general hospital
population with suspected infection. Even patients
presenting with modest dysfunction can deteriorate further,
emphasizing the seriousness of this condition and the need
for prompt and appropriate intervention, if not already
being instituted.
• In lay terms, sepsis is a life-threatening condition
that arises when the body’s response to an infection injures
its own tissues and organs.
• Patients with suspected infection who are likely to have a
prolonged ICU stay or to die in the hospital can be promptly
identified at the bedside with qSOFA, ie, alteration in mental
status, systolic blood pressure Š100 mm Hg, or respiratory rate
Š22/min.
• Septic shock is a subset of sepsis in which underlying
circulatory and cellular/metabolic abnormalities are profound
enough to substantially increase mortality.
• Patients with septic shock can be identified with a
clinical construct of sepsis with persisting hypotension
requiring vasopressors to maintain MAP Š65 mm Hg and
having a serum lactate level
>2 mmol/L (18 mg/dL) despite adequate volume resuscitation.
With these criteria, hospital mortality is in excess of 40%.

ICU, predictive validity was determined with 2 metrics for

each criterion: the area under the receiver operating
characteristic curve (AUROC) and the change in outcomes
comparing patients with a score of either 2 points or more
or fewer than 2 points in the different scoring systems9,27,30
across deciles of baseline risk. These criteria were also
analyzed in 4 external US and non-US data sets
containing data from more than 700 000 patients (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 set, 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 2 or 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).
Because SOFA is better known and simpler than the
Logistic Organ Dysfunction System, the task force
recommends using a change in baseline of the total SOFA
score of 2 points or more to represent organ dysfunction
(Box 3). The baseline SOFA score should be assumed to be
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mortality risk of approximately 10% in a general SOFA) and incor- porating altered mentation, systolic blood
hospital popula- tion with presumed infection.12 This pressure of 100 mm Hg or less, and respiratory rate of
is greater than the overall mor- tality rate of 8.1% for 22/min or greater, provides simple bedside criteria to identify
ST-segment elevation myocardial infarction,31 a adult patients with suspected infection who are likely to have
condition widely held to be life threatening by the poor outcomes (Box 4). Because predictive validity was
community and by clinicians. Depending on a unchanged (P = .55), the task force chose to empha- size
patient’s baseline level of risk, a SOFA score of 2 or altered mentation because it represents any Glasgow Coma
greater identified a 2- to 25-fold increased risk of
dying compared with patients with a SOFA score less
than 2.12
As discussed later, the SOFA score is not
intended to be used as a tool for patient
management but as a means to clinically char-
acterize a septic 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 used in
SOFA, but these require broader validation before
they can be incorporated into the clinical criteria
describing sepsis. Future iterations of the sepsis
definitions should include an updated SOFA score
with more optimal variable selection, 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
2 of 3 clinical variables— Glasgow Coma Scale score
of 13 or less, systolic blood pressure of 100 mm 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.12 This model was robust to multiple
sensitivity analyses including a more simple assessment
of altered mentation (Glasgow Coma Scale score
<15) and in the out-of-hospital, emergency
department, and ward settings within the external US
and non-US data sets.
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, sedative 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

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Scale score less than 15 and will reduce the measurement confounders in the hypotension- vasopressor relationship.
burden. Although qSOFA is less robust than a SOFA score of 2 By Delphi consensus process, 3 variables were
or greater in the ICU, it does not require laboratory tests and identified (hypotension, elevated lactate level, and a
can be assessed quickly and repeatedly. The task force sustained need for vaso- pressor therapy) to test in
suggests that qSOFA criteria be used to prompt clinicians to cohort studies, exploring alternative
further investigate for organ dys- function, to initiate or
escalate therapy as appropriate, and to con- sider referral to
critical care or increase the frequency of monitor- ing, if such
actions have not already been undertaken. The task force
considered that positive qSOFA criteria should also prompt
consideration of possible infection in patients not previously
recog- nized as infected.

Definition of Septic Shock

Septic shock is defined as a subset of sepsis in which
underlying cir- culatory and cellular metabolism abnormalities
are profound enough to substantially increase mortality (Box 3).
The 2001 task force defi- nitions described septic shock as
“a state of acute circulatory failure.”10 The task force
favored a broader view to differentiate sep- tic shock from
cardiovascular dysfunction alone and to recognize the
importance of cellular abnormalities (Box 3). There was
unanimous agreement that septic shock should reflect a more
severe illness with a much higher likelihood of death than
sepsis alone.

Clinical Criteria to Identify Septic Shock

Further details are provided in the accompanying
article by Shankar-Hari et al.13 First, a systematic review
assessed how cur- rent definitions were operationalized. This
informed a Delphi pro- cess conducted among the task force
members to determine the updated septic shock definition
and clinical criteria. This process was iterative and informed
by interrogation of databases, as sum- marized below.
The Delphi process assessed agreements on descriptions
of terms such as “hypotension,” “need for vasopressor therapy,”
“raised lactate,” and “adequate fluid resuscitation” for inclusion
within the new clinical criteria. The majority (n = 14/17;
82.4%) of task force members voting on this agreed that
hypotension should be de- noted as a mean arterial
pressure less than 65 mm Hg according to the pragmatic
decision that this was most often recorded in data sets
derived from patients with sepsis. Systolic blood pressure was
used as a qSOFA criterion because it was most widely
recorded in the elec- tronic health record data sets.
A majority (11/17; 64.7%) of the task force agreed,
whereas 2 (11.8%) disagreed, that an elevated lactate level is
reflective of cel- lular dysfunction in sepsis, albeit recognizing
that multiple factors, such as insufficient tissue oxygen
delivery, impaired aerobic respi- ration, accelerated aerobic
glycolysis, and reduced hepatic clear- ance, also contribute.32
Hyperlactatemia is, however, a reasonable marker of illness
severity, with higher levels predictive of higher mortality.33
Criteria for “adequate fluid resuscitation” or “need for
vasopressor therapy” could not be explicitly specified
because these are highly user dependent, relying on variable
monitoring modalities and hemodynamic targets for
treatment. 34 Other aspects of management, such as
sedation and volume status assessment, are also potential
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 Clinical Review & Education Special Communication Consensus Definitions for Sepsis and Septic
Shock
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combinations and different lactate thresholds. The first database
interrogated was the Surviving Sepsis Campaign’s international
multicenter registry of 28 150 infected patients with at least 2
SIRS criteria and at least 1 organ dysfunction criterion.
Hypotension was defined as a mean arterial pressure less than 65
mm Hg, the only available cutoff. A total of 18 840 patients
with vasopressor therapy, hypotension, or hyperlactatemia (>2
mmol/L [18 mg/dL]) after volume resuscitation were identified.
Patients with fluid- resistant hypotension requiring vasopressors and
with hyperlacta- temia were used as the referent group for
comparing between- group differences in the risk-adjusted odds
ratio for mortality. Risk adjustment was performed with a
generalized estimating equation population-averaged logistic
regression model with exchangeable correlation structure.
Risk-adjusted hospital mortality was significantly higher (P
< .001 compared with the referent group) in patients with fluid-
resistant hypotension requiring vasopressors and hyperlactatemia
(42.3% and 49.7% at thresholds for serum lactate level of
>2 mmol/L [18 mg/dL] or >4 mmol/L [36 mg/dL], respectively)
compared with either hyperlactatemia alone (25.7% and 29.9%
mortality for those with serum lactate level of >2 mmol/L
[18 mg/dL] and >4 mmol/L [36 mg/dL], respectively) or with fluid-
resistant hypotension requiring vasopressors but with lactate level of 2
mmol/L (18 mg/dL) or less (30.1%).
With the same 3 variables and similar categorization, the unad-
justed mortality in infected patients within 2 unrelated large elec-
tronic health record data sets (University of Pittsburgh Medical
Center [12 hospitals; 2010-2012; n = 5984] and Kaiser Permanente
Northern California [20 hospitals; 2009-2013; n = 54 135]) showed
reproducible results. The combination of hypotension, vasopressor use,
and lactate level greater than 2 mmol/L (18 mg/dL) identified
patients with mortality rates of 54% at University of Pittsburgh
Medical Center (n = 315) and 35% at Kaiser Permanente Northern
California (n = 8051). These rates were higher than the mortality
rates of 25.2% (n = 147) and 18.8% (n = 3094) in patients
with hypotension alone, 17.9% (n = 1978) and 6.8% (n = 30
209) in patients with lactate level greater than 2 mmol/L (18
mg/dL) alone, and 20% (n = 5984) and 8% (n = 54 135) in
patients with sepsis at University of Pittsburgh Medical Center and
Kaiser Permanente Northern California, respectively.
The task force recognized that serum lactate measurements are
commonly, but not universally, available, especially in developing
countries. Nonetheless, clinical criteria for septic shock were devel-
oped with hypotension and hyperlactatemia rather than either alone
because the combination encompasses both cellular dysfunction and
cardiovascular compromise and is associated with a significantly
higher risk-adjusted mortality. This proposal was approved by a ma-
jority (13/18; 72.2%) of voting members13 but warrants revisiting. The
Controversies and Limitations section below provides further dis-
cussion about the inclusion of both parameters and options for when
lactate level cannot be measured.

Recommendations for ICD Coding

and for Lay Definitions
In accordance with the importance of accurately applying diagnos-
tic codes, Table 2 details how the new sepsis and septic shock clini-

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cal criteria correlate with ICD-9-CM and ICD-10 codes. The
Table 2. Terminology and International Classification of Diseases Coding
task force also endorsed the recently published lay
definition that “sepsis is a life-threatening condition that Current Guidelines
and Terminology Sepsis Septic Shock
arises when the body’s response to infection injures its own
1991 and 2001 Severe sepsis Septic shock13
tissues,” which is consistent with the newly proposed consensus Sepsis-induced
definitions described above.35 To trans- mit the importance terminology9,10 hypoperfusion
2015 Definition Sepsis is Septic shock is a subset of
of sepsis to the public at large, the task force emphasizes life-threatening organ sepsis in which underlying
that sepsis may portend death, especially if not recog- nized dysfunction caused by a circulatory and
dysregulated host cellular/metabolic
early and treated promptly. Indeed, despite advances that response to infection abnormalities are profound
include vaccines, antibiotics, and acute care, sepsis remains the enough to substantially
increase mortality
pri- mary cause of death from infection. Widespread
2015 Clinical Suspected or Sepsisa
educational cam- paigns are recommended to better inform criteria documented infection and
the public about this lethal condition. 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 meet 2 or more qSOFA or SOFA criteria should
despite not fluid
adequate
resuscitation13
lead to a
deferral of
investigation
Recommended or treatment of infection or to a delay in any other
There are inherent challenges in defining sepsis and septic primary ICD
aspect
codesa of care deemed necessary by the practitioners. qSOFA can be
shock. First and foremost, sepsis is a broad term applied rapidly
ICD-9 995.92 785.52
to an incom- pletely understood process. There are, as yet, no
ICD-10a R65.20 R65.21
simple and unam- biguous clinical criteria or biological, imaging,
Framework for Identify suspected infection by using concomitant orders
or laboratory features that uniquely identify a septic patient. implementation for blood cultures and antibiotics (oral or parenteral) in a
The task force recognized the impossibility of trying to achieve for coding and specified periodb
research Within specified period around suspected infectionc:
total consensus on all points. Pragmatic compromises were 1. Identify sepsis by using a clinical criterion for
necessary, so emphasis was placed on generalizability and the life-threatening organ dysfunction
2. Assess for shock criteria, using administration of
use of readily measurable identifiers that could best capture vasopressors, MAP <65 mm Hg, and lactate >2 mmol/L
the current conceptualization of underlying mechanisms. The (18 mg/dL)d
detailed, data-guided deliberations of the task force during an
18-month period and the peer review provided by bodies
approached for endorsement highlighted multiple areas for
discussion. It is useful to identify these issues and provide
justifica- tions for the final positions adopted.
The new definition of sepsis reflects an up-to-date view of
patho- biology, particularly in regard to what distinguishes
sepsis from un- complicated infection. The task force also
offers easily measurable clinical criteria that capture the
essence of sepsis yet can be trans- lated and recorded
objectively (Figure). Although these criteria cannot be all-
encompassing, they are simple to use and offer con- sistency
of terminology to clinical practitioners, researchers, admin-
istrators, and funders. The physiologic and biochemical tests
re- quired to score SOFA are often included in routine patient
care, and scoring can be performed retrospectively.
The initial, retrospective analysis indicated that qSOFA
could be a useful clinical tool, especially to physicians and
other practi- tioners working outside the ICU (and perhaps
even outside the hospital, given that qSOFA relies only on
clinical examination find- ings), to promptly identify infected
patients likely to fare poorly. However, because most of the
data were extracted from extracted US databases, the task
force strongly encourages prospective vali- dation in multiple US
and non-US health care settings to confirm its robustness and
potential for incorporation into future iterations of the
definitions. This simple bedside score may be particularly rel-
evant in resource-poor settings in which laboratory data are
not readily available, and when the literature about sepsis
epidemiol- ogy is sparse.
Neither qSOFA nor SOFA is intended to be a stand-alone
defi- nition of sepsis. It is crucial, however, that failure to

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Abbreviations: ICD, International Classification of Diseases; MAP,

mean arterial pressure; SOFA, Sequential [Sepsis-related] Organ
Failure Assessment.27
a
Included training codes.
b
Suspected infection could be defined as the concomitant
administration of oral or parenteral antibiotics and sampling of
body fluid cultures (blood, urine, cerebrospinal fluid,
peritoneal, etc). For example, if the culture is obtained, the
antibiotic is required to be administered within 72 hours,
whereas if the antibiotic is first, the culture is required within
24 hours.12
c
Considers a period as great as 48 hours before and up to 24
hours after onset of infection, although sensitivity analyses
have tested windows as short as
3 hours before and 3 hours after onset of infection.12
d
With the specified period around suspected infection, assess for
shock criteria, using any vasopressor initiation (eg, dopamine,
norepinephrine, epinephrine, vasopressin, phenylephrine), any
lactate level >2 mmol/L (18 mg/dL), and mean arterial
pressure <65 mm Hg. These criteria require adequate fluid
resuscitation as defined by the Surviving Sepsis Campaign
guidelines.4

scored at the bedside without the need for blood

tests, and it is hoped that it will facilitate prompt
identification of an infection that poses a greater
threat to life. If appropriate laboratory tests have not
already been undertaken, this may prompt testing to
identify biochemical organ dysfunction. These data will
primarily aid patient management but will also enable
subsequent SOFA scoring. The task force wishes to
stress that SIRS criteria may still remain useful for
the identification of infection.
Some have argued that lactate measurement
should be man- dated as an important biochemical
identifier of sepsis in an infected patient. Because
lactate measurement offered no meaningful change
in the predictive validity beyond 2 or more qSOFA
criteria in the identification of patients likely to be
septic, the task force could not justify the added
complexity and cost of lactate measurement
alongside these simple bedside criteria. The task
force recommen- dations should not, however,
constrain the monitoring of lactate as a guide to
therapeutic response or as an indicator of illness
severity.

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Shock Education
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Figure. Operationalization of Clinical Criteria Identifying Patients With Sepsis and Septic Shock

Patient with suspected

infection

qSOFA ≥2? Monitor clinical condition;

No Sepsis still No
(see A ) reevaluate for possible sepsis
suspected?
if clinically indicated
Yes Yes

Assess for evidence

of organ dysfunction
A qSOFA Variables

Monitor clinical condition; Respiratory rate

SOFA ≥2? No
reevaluate for possible sepsis Mental status
(see B )
if clinically indicated Systolic blood pressure
Yes

Sepsis
B SOFA Variables
PaO2/FiO2 ratio
Despite adequate fluid resuscitation, Glasgow Coma Scale score
1. vasopressors required to maintain
No Mean arterial pressure
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.

Our approach to hyperlactatemia within the clinical account their age- dependent variation in normal
criteria for septic shock also generated conflicting views. physiologic ranges and in patho- physiologic responses.
Some task force members suggested that elevated lactate
levels represent an important marker of “cryptic shock” in the
absence of hypotension. Others voiced concern about its
specificity and that the nonavail- ability of lactate
measurement in resource-poor settings would preclude a
diagnosis of septic shock. No solution can satisfy all con-
cerns. Lactate level is a sensitive, albeit nonspecific, stand-
alone indicator of cellular or metabolic stress rather than
“shock.”32 How- ever, the combination of hyperlactatemia with
fluid-resistant hypo- tension identifies a group with
particularly high mortality and thus offers a more robust
identifier of the physiologic and epide- miologic concept of
septic shock than either criterion alone. Identi- fication of
septic shock as a distinct entity is of epidemiologic rather than
clinical importance. Although hyperlactatemia and hypoten-
sion are clinically concerning as separate entities, and
although the proposed criteria differ from those of other
recent consensus statements,34 clinical management should
not be affected. The greater precision offered by data-driven
analysis will improve reporting of both the incidence of septic
shock and the associated mortality, in which current figures
vary 4-fold. 3 The criteria may also enhance insight into
the pathobiology of sepsis and septic shock. In settings in
which lactate measurement is not avail- able, the use of a
working diagnosis of septic shock using hypoten- sion and
other criteria consistent with tissue hypoperfusion (eg,
delayed capillary refill36) may be necessary.
The task force focused on adult patients yet recognizes the
need to develop similar updated definitions for pediatric
populations and the use of clinical criteria that take into
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Implications
The task force has generated new definitions that incorporate an
up-to-date understanding of sepsis biology, including organ dys-
function (Box 3). However, the lack of a criterion standard, similar
to its absence in many other syndromic conditions, precludes
unambiguous validation and instead requires approximate estima-
tions of performance across a variety of validity domains, as out-
lined above. To assist the bedside clinician, and perhaps prompt an
escalation of care if not already instituted, simple clinical criteria
(qSOFA) that identify patients with suspected infection who are
likely to have poor outcomes, that is, a prolonged ICU course and
death, have been developed and validated.
This approach has important epidemiologic and investigative
implications. The proposed criteria should aid diagnostic categori-
zation once initial assessment and immediate management are
completed. qSOFA or SOFA may at some point be used as
entry criteria for clinical trials. There is potential conflict with cur-
rent organ dysfunction scoring systems, early warning scores,
ongoing research studies, and pathway developments. Many of
these scores and pathways have been developed by consensus,
whereas an important aspect of the current work is the interroga-
tion of data, albeit retrospectively, from large patient populations.
The task force maintains that standardization of definitions
and clinical criteria is crucial in ensuring clear communication and
a more accurate appreciation of the scale of the problem of
sep- sis. An added challenge is that infection is seldom
confirmed microbiologically when treatment is started; even
when micro- biological tests are completed, culture-positive
“sepsis” is observed in only 30% to 40% of cases. Thus, when
sepsis epide-

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miology is assessed and reported, operationalization will enhanced collection of data will fuel their continued
neces- sarily involve proxies such as antibiotic reevaluation and revision.
commencement or a clini- cally determined probability of
infection. Future epidemiology studies should consider
reporting the proportion of microbiology- positive sepsis.
Greater clarity and consistency will also facilitate research Conclusions
and more accurate coding. Changes to ICD coding may take These updated definitions and clinical criteria should clarify
several years to enact, so the recommendations provided in long- used descriptors and facilitate earlier recognition and
Table 2 demon- strate how the new definitions can be more timely management of patients with sepsis or at risk of
applied in the interim within the current ICD system. developing it. This process, however, remains a work in
The debate and discussion that this work will progress. As is done with soft- ware and other coding
inevitably generate are encouraged. Aspects of the new updates, the task force recommends that the new definition
definitions do indeed rely on expert opinion; further be designated Sepsis-3, with the 1991 and 2001 it- erations
understanding of the biol- ogy of sepsis, the availability of being recognized as Sepsis-1 and Sepsis-2, respectively, to
new diagnostic approaches, and emphasize the need for future iterations.

ARTICLE INFORMATION data in the study and take responsibility for

Acquisition, analysis, or interpretation of data: All authors.
Author Affiliations: Bloomsbury Institute of the integrity of the data and the accuracy of the
Drafting of the manuscript: Singer, Deutschman, Seymour,
Intensive Care Medicine, University College data analysis.
Shankar-Hari, Angus.
London, London, United Kingdom (Singer); Study concept and design: All authors.
Critical revision of the manuscript for important
Hofstra–Northwell School of Medicine, intellectual content: All authors.
Feinstein Institute for Medical Research, New Statistical analysis: Shankar-Hari, Seymour. Obtained
Hyde Park, New York (Deutschman); funding: Deutschman, Chiche, Coopersmith.
Department of Critical Care and Emergency Administrative, technical, or material support: Singer,
Medicine, University of Pittsburgh School of Deutschman, Chiche, Coopersmith, Levy, Angus.
Medicine, Pittsburgh, Pennsylvania Study supervision: Singer, Deutschman.
(Seymour); Department of Critical Care Drs Singer and Deutschman are joint first authors.
Medicine, Guy’s and St Thomas’ NHS
Conflict of Interest Disclosures: All authors have completed
Foundation Trust, London, United Kingdom
and submitted the ICMJE Form for Disclosure of Potential
(Shankar-Hari); Department of Critical Care
Conflicts of Interest.
Medicine, University of Versailles, France
Dr Singer reports serving on the advisory boards of
(Annane); Center for Sepsis Control and Care,
InflaRx, Bayer, Biotest, and Merck and that his institution
University Hospital, Jena, Germany (Bauer);
has received grants from the European Commission, UK
Australian and New Zealand Intensive Care
National Institute of Health Research, Immunexpress,
Research Centre, School of Public Health and
DSTL, and Wellcome Trust. Dr Deutschman reports holding
Preventive Medicine, Monash University,
patents on materials not related to this work and
Melbourne, and Austin Hospital, Melbourne,
receiving travel/accommodations and related expenses for
Victoria, Australia (Bellomo); Vanderbilt Institute
participation in meetings paid by the Centers for Disease
for Clinical and Translational Research,
Control and Prevention, World Federation of Societies of
Vanderbilt University, Nashville, Tennessee
Intensive and Critical Care, Pennsylvania Assembly of
(Bernard); Réanimation Médicale-Hôpital Cochin,
Critical Care Medicine/PA Chapter, Society of Critical
Descartes University, Cochin Institute, Paris, France
Care Medicine (SCCM)/Penn State–Hershey Medical
(Chiche); Critical Care Center, Emory University
Center, Society of Critical Care Medicine, Northern Ireland
School of Medicine, Atlanta, Georgia
Society of Critical Care Medicine, International Sepsis
(Coopersmith); Washington University School of
Forum, Department of Anesthesiology, Stanford
Medicine, St Louis, Missouri (Hotchkiss);
University, Acute Dialysis Quality Initiative, and European
Infectious Disease Section, Division of
Society of Intensive Care Medicine (ESICM). Dr Seymour
Pulmonary and Critical Care Medicine, Brown
reports receiving personal fees from Beckman Coulter
University School of Medicine, Providence,
and a National Institutes of Health (NIH) grant awarded
Rhode Island (Levy, Opal); Department of
to his institution. Dr Bauer reports support for travel to
Surgery, University of Toronto, Toronto,
meetings for the study from ESICM, payment for
Ontario, Canada (Marshall); Emory University
speaking from CSL Behring, grants to his institution from
School of Medicine and Grady Memorial
Jena University Hospital, and patents held by Jena
Hospital, Atlanta, Georgia (Martin); Trauma,
University Hospital. Dr Bernard reports grants from
Emergency & Critical Care Program, Sunnybrook
AstraZeneca for activities outside the submitted work.
Health Sciences Centre, Toronto, Ontario,
Dr Chiche reports consulting for Nestlé and Abbott and
Canada (Rubenfeld); Interdepartmental Division
honoraria for speaking from GE Healthcare and Nestlé. Dr
of Critical Care, University of Toronto
Coopersmith reports receiving grants from the NIH for work
(Rubenfeld); Department of Infectious
not related to this article. Dr Coopersmith also reports
Diseases, Academisch Medisch Centrum,
bring president-elect and president of SCCM when the
Amsterdam, the Netherlands (van der Poll);
task force was meeting and the article was being
Department of Intensive Care, Erasme
drafted. A stipend was paid to Emory University for
University Hospital, Brussels, Belgium
(Vincent); Department of Critical Care Medicine,
University of Pittsburgh and UPMC Health
System, Pittsburgh, Pennsylvania (Angus);
Associate Editor, JAMA (Angus).
Author Contributions: Drs Singer and
Deutschman had full access to all of the
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 Clinical Review & Education Special Communication Consensus Definitions for Sepsis and Septic
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his time spent in these roles. Dr
Hotchkiss reports consulting on sepsis
for GlaxoSmithKline, Merck, and
Bristol-Meyers Squibb and reports
that his institution received grant
support from Bristol- Meyers Squibb
and GlaxoSmithKline, as well as the
NIH, for research on sepsis. Dr
Marshall reports serving on the data
and safety monitoring board
(DSMB) of AKPA Pharma and
Spectral Medical Steering
Committee and receiving payment
for speaking from Toray Ltd and
Uni-Labs. Dr Martin reports serving
on the board for SCCM and Project
Help, serving on the DSMB for
Cumberland Pharmaceuticals and
Vanderbilt University, serving on the
medical advisory board for Grifols
and Pulsion Medical Systems, and
grants to his institution from NIH,
the Food and Drug Administration,
Abbott, and Baxter. Dr Opal reports
grants from GlaxoSmithKline, Atoxbio,
Asahi-Kasei, Ferring, Cardeas, and
Arsanis outside the submitted work;
personal fees from Arsanis, Aridis,
Bioaegis, Cyon, and Battelle; and
serving on the DSMB for Achaogen,
Spectral Diagnostics, and Paratek. No
other disclosures were reported.
Funding/Support: This work was
supported in part by a grant from
the Society of Critical Care Medicine
(SCCM) and the European Society of
Intensive Care Medicine (ESICM).
Role of the Funder/Sponsor: These
funding bodies appointed cochairs
but otherwise had no role in the
design and conduct of the work; the
collection, management, analysis,
and interpretation of the data;
preparation of the manuscript; or
decision to submit the manuscript
for publication. As other national
and international societies, they
were asked for comment and
endorsement.
Disclaimer: Dr Angus, JAMA Associate
Editor, had no role in the
evaluation of or decision to
publish this article.
Endorsing Societies: Academy of
Medical Royal Colleges (UK);
American Association of Critical Care
Nurses; American Thoracic Society
(endorsed August 25, 2015);
Australian–New Zealand Intensive
Care Society (ANZICS); Asia Pacific
Association of Critical Care
Medicine; Brasilian Society of
Critical Care; Central American and
Caribbean Intensive Therapy
Consortium; Chinese Society of
Critical Care Medicine; Chinese
Society of Critical Care Medicine–
China Medical Association; Critical
Care Society of South Africa;
Emirates Intensive Care Society;
European Respiratory Society;
European Resuscitation Council;
European Society of Clinical
Microbiology and Infectious

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Diseases and its Study Group of mortality of hospital-treated sepsis: current estimates and
Bloodstream Infections and Sepsis; limitations. Am J Respir Crit Care Med. 2015.
European Society of Emergency Medicine;
European Society of Intensive Care 8. Iwashyna TJ, Ely EW, Smith DM, Langa KM.
Medicine; European Society of Paediatric and Long-term cognitive impairment and functional
Neonatal Intensive Care; German Sepsis disability among survivors of severe sepsis.
Society; Indian Society of Critical Care JAMA. 2010;304(16):1787-1794.
Medicine; International Pan Arabian Critical Care 9. Bone RC, Balk RA, Cerra FB, et al. American
Medicine Society; Japanese Association for Acute College of Chest Physicians/Society of Critical
Medicine; Japanese Society of Intensive Care Care Medicine Consensus Conference: definitions
Medicine; Pan American/Pan Iberian Congress of for sepsis and organ failure and guidelines for the
Intensive Care; Red Intensiva (Sociedad Chilena use of innovative therapies in sepsis. Crit Care
de Medicina Crítica y Urgencias); Sociedad Med. 1992;20(6):864-874.
Peruana de Medicina Critica; Shock Society; 10. Levy MM, Fink MP, Marshall JC, et al;
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Society of Critical Care Medicine; Surgical SCCM/ESICM/ACCP/ATS/SIS International Sepsis
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Additional Contributions: The task force would
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MD, PhD, University of Michigan; Vincent Liu, doi: 10.1001/jama.2016.0288.
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California; Thomas Rea, MD, MPH, University of Assessment of definition and clinical criteria for
Washington; and Gary Phillips, MAS, Ohio septic shock. JAMA.doi:10.1001/jama.2016.0289
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assistance, and the administrations and
and septic shock. N Engl J Med. 2013;369(9):840-
leadership of SCCM and ESICM for facilitating
851.
its work. Payment was provided to the
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to support the work of Mr Phillips. der Poll T. Host innate immune responses to
sepsis. Virulence. 2014;5(1):36-44.
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