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ALID AND RELIABLE DEFINI - American-European Consensus Conference (AECC); since then, issues regard-
tions are essential to con- ing the reliability and validity of this definition have emerged. Using a con-
duct epidemiological stud-
sensus process, a panel of experts convened in 2011 (an initiative of the Eu-
ies succ e s s f u lly a n d t o
facilitate enrollment of a consistent pa- ropean Society of Intensive Care Medicine endorsed by the American Thoracic
tient phenotype into clinical trials.1 Cli- Society and the Society of Critical Care Medicine) developed the Berlin Defi-
nicians also need such definitions to nition, focusing on feasibility, reliability, validity, and objective evaluation of
implement the results of clinical trials, its performance. A draft definition proposed 3 mutually exclusive categories
discuss prognosis with families, and of ARDS based on degree of hypoxemia: mild (200 mm Hg⬍PaO2/FIO2 ⱕ300
plan resource allocation. mm Hg), moderate (100 mm Hg⬍PaO2/FIO2 ⱕ200 mm Hg), and severe (PaO2/
Following the initial description of FIO2 ⱕ100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic se-
acute respiratory distress syndrome
verity, respiratory system compliance (ⱕ40 mL/cm H2O), positive end-
(ARDS) by Ashbaugh et al2 in 1967,
multiple definitions were proposed and expiratory pressure (ⱖ10 cm H2O), and corrected expired volume per minute
used until the 1994 publication of the (ⱖ10 L/min). The draft Berlin Definition was empirically evaluated using patient-
American-European Consensus Con- level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data
ference (AECC) definition.3 The AECC sets and 269 patients with ARDS from 3 single-center data sets containing physi-
defined ARDS as the acute onset of hy- ologic information. The 4 ancillary variables did not contribute to the predic-
poxemia (arterial partial pressure of tive validity of severe ARDS for mortality and were removed from the defini-
oxygen to fraction of inspired oxygen tion. Using the Berlin Definition, stages of mild, moderate, and severe ARDS
[PaO2/FIO2] ⱕ200 mm Hg) with bilat-
were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95%
eral infiltrates on frontal chest radio-
graph, with no evidence of left atrial hy- CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P⬍.001) and in-
pertension. A new overarching entity— creased median duration of mechanical ventilation in survivors (5 days; inter-
acute lung injury (ALI)—was also quartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively;
described, using similar criteria but with P⬍.001). Compared with the AECC definition, the final Berlin Definition had
less severe hypoxemia (PaO2/FIO2 ⱕ300 better predictive validity for mortality, with an area under the receiver operat-
mm Hg).3 ing curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553;
The AECC definition was widely
P⬍.001). This updated and revised Berlin Definition for ARDS addresses a num-
adopted by clinical researchers and
clinicians and has advanced the ber of the limitations of the AECC definition. The approach of combining con-
knowledge of ARDS by allowing the sensus discussions with empirical evaluation may serve as a model to create
acquisition of clinical and epidemio- more accurate, evidence-based, critical illness syndrome definitions and to bet-
logical data, which in turn have led to ter inform clinical care, research, and health services planning.
improvements in the ability to care JAMA. 2012;307(23):2526-2533
for patients with ARDS. However, Published online May 21, 2012. doi:10.1001/jama.2012.5669 www.jama.com
after 18 years of applied research, a
criteria for defining acute, sensitivity *Authors/Writing Committee and the Members of the
number of issues regarding various ARDS Definition Task Force are listed at the end of
of PaO2/FIO2 to different ventilator set-
criteria of the AECC definition have this article.
tings, poor reliability of the chest Corresponding Author: Gordon D. Rubenfeld, MD,
emerged, including a lack of explicit
radiograph criterion, and difficulties MSc, Program in Trauma, Emergency, and Critical Care,
Sunnybrook Health Sciences Center, 2075 Bayview
distinguishing hydrostatic edema Ave, Toronto, ON M4N 3M5, Canada (gordon
For editorial comment see p 2542.
(TABLE 1).4 .rubenfeld@sunnybrook.ca).
2526 JAMA, June 20, 2012—Vol 307, No. 23 ©2012 American Medical Association. All rights reserved.
tion. Patients may qualify as having a low respiratory system compliance definition and the draft Berlin
ARDS as long as they have respiratory (⬍40 mL/cm H2O), a high V̇ECORR (⬎10 Definition.
failure not fully explained by cardiac L/min), or both. These variables were Compared with patients from the
failure or fluid overload as judged by identified for further study during the population-based cohorts, patients from
the treating physician using all avail- evaluation phase. clinical trials and the academic cen-
able data. If no ARDS risk factor (eTable The panel considered a number of ters cohorts were younger, had more se-
1) is apparent, some objective evalua- additional measures to improve speci- vere hypoxemia, and had more opaci-
tion (eg, with echocardiography) is re- ficity and face validity for the in- ties on chest radiographs. The cohort
quired to help eliminate the possibil- creased pulmonary vascular permeabil- of patients from the clinical trials had
ity of hydrostatic edema. ity and loss of aerated lung tissue that the lowest mortality, likely reflecting the
Oxygenation. The term acute lung in- are the hallmarks of ARDS, including inclusion and exclusion criteria of the
jury as defined by the AECC was re- CT scanning, and inflammatory or ge- trials.31 The cohort of patients from aca-
moved, due to the perception that clini- netic markers (eTable 2). The most demic centers had the highest mortal-
cians were misusing this term to refer to common reasons for exclusion of these ity and the lowest percentage of trauma
a subset of patients with less severe hy- measures were lack of routine avail- patients, reflecting the referral popu-
poxemia rather than its intended use as ability, lack of safety of the measure in lation (eTable 3).
an inclusive term for all patients with the critically ill patients, or a lack of dem- There were 269 patients in the physi-
syndrome. Positive end-expiratory pres- onstrated sensitivity, specificity, or both ological database with sufficient data to
sure can markedly affect PaO2/FIO25,6; for use as a defining characteristic for classify ARDS by the AECC defini-
therefore, a minimum level of PEEP (5 ARDS. tion, although the numbers of pa-
cm H2O), which can be delivered non- Empirical Evaluation of the Draft tients in each cohort were small. Pa-
invasively in mild ARDS, was included Definition. tients in the Turin cohort had worse
in the draft definition of ARDS. A mini- Patients. A total of 4188 patients in the PaO2/FIO2 ratios and had higher mor-
mum PEEP level of 10 cm H2O was pro- clinical database had sufficient data to tality than the other studies (eTable 4).
posed and empirically evaluated for the classify as having ARDS by the AECC Evaluation of Ancillary Variables. The
severe ARDS category. definition. Of these patients, 518 (12%) draft Berlin Definition for severe ARDS
Additional Physiologic Measurements. could not be classified by the draft Ber- that included a PaO2/FIO2 of 100 mm Hg
Compliance of the respiratory system lin Definition because PEEP was miss- or less, chest radiograph with 3 or 4
largely reflects the degree of lung vol- ing or was less than 5 cm H2O. Pa- quadrants with opacities, PEEP of at least
ume loss.2 Increased dead space is com- tients who could not be classified by the 10 cm H2O, and either a CRS of 40 mL/cm
mon in patients with ARDS and is asso- draft Berlin Definition had a mortality H2O or less or a V̇ECORR of at least 10
ciated with increased mortality. 2 4 rate of 35% (95% CI, 31%-39%), a me- L/min identified a smaller set of pa-
However, because the measurement of dian (interquartile range [IQR]) of 19 tients with identical mortality to the sim-
dead space is challenging, the panel chose (1-25) ventilator-free days, and a me- pler severe ARDS category of PaO2/FIO2
minute ventilation standardized at a dian (IQR) duration of mechanical ven- of 100 mm Hg or less (TABLE 2). To ad-
PaCO2 of 40 mm Hg (V̇ECORR = minute tilation in survivors of 4 (2-8) days. dress the possibility that the CRS and
ventilation ⫻ Pa CO 2 /40) as a surro- These patients were excluded from V̇ECORR thresholds might be different in
gate.22 The draft definition of severe analyses of the draft Berlin Definition patients with higher body weight, we
ARDS included the requirement of either and comparisons between the AECC evaluated weight-adjusted cutoffs for
©2012 American Medical Association. All rights reserved. JAMA, June 20, 2012—Vol 307, No. 23 2529
these variables in one of the cohorts. 27%-30%) of patients met criteria for tients with moderate ARDS at baseline
There was no significant difference in the severe ARDS. Mortality increased with progressed to severe ARDS within 7 days.
predictive validity of the weight- stages of ARDS from mild (27%; 95% All differences between outcome vari-
adjusted criteria. The consensus panel re- CI, 24%-30%) to moderate (32%; 95% ables across categories of modified AECC
viewed these results and considered the CI, 29%-34%) to severe (45%; 95% CI, (ALI non-ARDS and ARDS alone) and
lack of evidence for predictive validity of 42%-48%). Median (IQR) ventilator- across categories of Berlin Definition
these ancillary variables and their po- free days declined with stages of ARDS (mild, moderate, and severe) were sta-
tential contribution to face validity and from mild (20 [1-25] days) to moder- tistically significant (P⬍.001).
construct validity and decided to use the ate (16 [0-23] days) to severe (1 [0- Compared with the AECC defini-
simpler definition for severe ARDS that 20] day). Median (IQR) duration of me- tion, the final Berlin Definition had bet-
relied on oxygenation alone. chanical ventilation in survivors ter predictive validity for mortality with
The Berlin Definition. The final Ber- increased with stages of ARDS from an AUROC of 0.577 (95% CI, 0.561-
lin Definition of ARDS is shown in mild (5 [2-11] days) to moderate (7 [4- 0.593) vs 0.536 (95% CI, 0.520-
TABLE 3. Twenty-two percent (95% CI, 14] days) to severe (9 [5-17] days). 0.553; P⬍.001), with the difference in
21%-24%) of patients met criteria for Using the Berlin Definition, 29% (95% AUROC of 0.041 (95% CI, 0.030-
mild ARDS (which is comparable with CI, 26%-32%) of patients with mild 0.050). To ensure that missing PEEP
the ALI non-ARDS category of the ARDS at baseline progressed to moder- data in one of the cohorts did not bias
AECC definition; TABLE 4), 50% (95% ate ARDS and 4% (95% CI, 3%-6%) pro- the results, the regression analysis was
CI, 48%-51%) of patients met criteria gressed to severe ARDS within 7 days; repeated without this cohort and
for moderate ARDS, and 28% (95% CI, and 13% (95% CI, 11%-14%) of pa- yielded similar results.
The Berlin Definition performed simi-
larly in the physiological database as in
Table 3. The Berlin Definition of Acute Respiratory Distress Syndrome
the clinical database (TABLE 5, eFigure
Acute Respiratory Distress Syndrome
1, and eFigure 2). Twenty-five percent
Timing Within 1 week of a known clinical insult or new or worsening respiratory
symptoms (95% CI, 20%-30%) of patients met
Chest imaging a Bilateral opacities—not fully explained by effusions, lobar/lung collapse, or criteria for mild ARDS, 59% (95% CI,
nodules 54%-66%) of patients met criteria for
Origin of edema Respiratory failure not fully explained by cardiac failure or fluid overload moderate ARDS, and 16% (95% CI, 11%-
Need objective assessment (eg, echocardiography) to exclude hydrostatic
edema if no risk factor present
21%) of patients met criteria for severe
Oxygenation b ARDS. Mortality increased with stages of
Mild 200 mm Hg ⬍ PaO2/FIO2 ⱕ 300 mm Hg with PEEP or CPAP ⱖ5 cm H2O c ARDS from mild (20%; 95% CI, 11%-
Moderate 100 mm Hg ⬍ PaO2/FIO2 ⱕ 200 mm Hg with PEEP ⱖ5 cm H2O 31%) to moderate (41%; 95% CI, 33%-
Severe PaO2/FIO2 ⱕ 100 mm Hg with PEEP ⱖ5 cm H2O 49%) to severe (52%; 95% CI, 36%-
Abbreviations: CPAP, continuous positive airway pressure; FIO2, fraction of inspired oxygen; PaO2, partial pressure of 68%), with P = .001 for differences in
arterial oxygen; PEEP, positive end-expiratory pressure.
a Chest radiograph or computed tomography scan. mortality across stages of ARDS. Me-
b If altitude is higher than 1000 m, the correction factor should be calculated as follows: [PaO /FIO ⫻(barometric pressure/
760)].
2 2
dian (IQR) ventilator-free days de-
c This may be delivered noninvasively in the mild acute respiratory distress syndrome group. clined with stages of ARDS from mild
2530 JAMA, June 20, 2012—Vol 307, No. 23 ©2012 American Medical Association. All rights reserved.
(8.5 [0-23.5] days) to moderate (0 [0- tients with severe ARDS that included were subjected to evaluation, these
16.5] days) to severe (0 [0-6.5] days), 15% of the entire ARDS population and parameters did not identify a group of
with P=.003 for differences in ventilator- had a mortality of 52% (95% CI, 48%- patients with higher mortality and were
free days across stages of ARDS. Me- 56%). Patients with severe ARDS who excluded from the final Berlin Defini-
dian (IQR) duration of mechanical ven- did not meet the higher-risk subset cri- tion after further consensus discus-
tilation in survivors increased with stages teria included 13% of the entire ARDS sion. Without this evaluation, a need-
of ARDS from mild (6.0 [3.3-20.8] days) population and had a mortality rate of lessly complex ARDS definition would
to moderate (12.0 [5.0-19.3] days) to se- 37% (95% CI, 33%-41%). The differ- have been proposed. However, static re-
vere (19.0 [9.0-48.0] days), with P=.045 ence between the mortality of patients spiratory system compliance and an un-
for differences in duration of mechani- with higher-risk severe ARDS and pa- derstanding of minute ventilation are
cal ventilation in survivors across stages tients with severe ARDS who did not important variables for clinicians to
of ARDS. meet these criteria was statistically sig- consider in managing patients with
Using the Berlin Definition, stages of nificant (P ⬍ .001). ARDS, even though those variables were
mild, moderate, and severe ARDS had in- not included as part of the defini-
creased mean lung weight by CT scan Comment tion.32
(1371 mg; 95% CI, 1268-1473; 1556 mg; Developing and disseminating formal The Berlin Definition addresses some
95% CI, 1474-1638; and 1828 mg; 95% definitions for clinical syndromes in of the limitations of the AECC defini-
CI, 1573-2082; respectively) and in- critically ill patients are essential for re- tion, including clarification of the ex-
creased mean shunt (21%; 95% CI, 16%- search and clinical practice. Although clusion of hydrostatic edema and add-
26%; 29%; 95% CI, 26%-32%; and 40%; previous proposals have relied solely on ing minimum ventilator settings, and
95% CI, 31%-48%; respectively). Com- the consensus process, this is to our provides slight improvement in pre-
parisons of lung weight and shunt (from knowledge the first attempt in critical dictive validity. Our study presents data
the single site providing these data) care to link an international consen- on the outcomes of patients with ARDS
across categories of modified AECC (ALI sus panel endorsed by professional so- defined according to the Berlin Defini-
non-ARDS and ARDS alone) and across cieties with an empirical evaluation. tion in a large heterogeneous cohort of
categories of Berlin Definition (mild, The draft Berlin Definition classi- patients including patients managed
moderate, and severe) were statistically fied patients with ARDS into 3 inde- with modern approaches to lung pro-
significant (P⬍.001) (Table 5, eFigure pendent categories but relied on ancil- tective ventilation. Estimates of the
3, and eFigure 4). lary variables (severity of chest prevalence and clinical outcomes of
In a post hoc analysis, combining a radiograph, PEEP ⱖ10 cm H2O, CRS mild, moderate, and severe ARDS can
PaO2/FIO2 of 100 mm Hg or less with ⱕ40 mL/cm H 2 O, and V̇ E CORR ⱖ10 be assessed from this database for re-
either a Crs of 20 mL/cm H2O or less or L/min) in addition to oxygenation to de- search and health services planning.
a V̇ECORR of at least 13 L/min identified fine the severe ARDS group. When the Acute respiratory distress syndrome is
a higher-risk subgroup among pa- ancillary variables selected by the panel a heterogeneous syndrome with com-
©2012 American Medical Association. All rights reserved. JAMA, June 20, 2012—Vol 307, No. 23 2531
plex pathology and mechanisms. The missing data seem unlikely because our Berlin Definition for ARDS may serve as
proposed definition does not resolve this results were robust to sensitivity analy- an example for linking consensus defi-
problem. Investigators may choose to de- ses that excluded individual cohorts. nition activities with empirical research
sign future trials using 1 or more of the Fourth, it is possible that the ancillary to better inform clinical care, research,
ARDS subgroups as a base study popu- variables did not identify a higher-risk and health services planning.
lation, which may be further refined subset because the number of quadrants Published Online: May 21, 2012. doi:10.1001
using criteria specific to the putative on the chest radiograph cannot be as- /jama.2012.5669
Authors/Writing Committee: V. Marco Ranieri, MD
mechanism of action of the interven- sessed reliably, PEEP was not used in a (Department of Anesthesia and Intensive Care Medi-
tion (eg, IL-6 levels for an anti–IL-6 trial predictable fashion, or CRS and V̇ECORR cine, University of Turin, Turin, Italy); Gordon D.
or more stringent hypoxemia criteria for were not accurately measured. However, Rubenfeld, MD, MSc (Program in Trauma, Emer-
gency, and Critical Care, Sunnybrook Health Sci-
a study on extracorporeal membrane if this is true, it is likely also to be true in ences Center, and Interdepartmental Division of Criti-
oxygenation). Furthermore, some vari- future studies and in clinical practice be- cal Care Medicine, University of Toronto, Toronto,
Ontario, Canada); B. Taylor Thompson, MD (Depart-
ables that were excluded from the Ber- cause the study database was constructed ment of Medicine, Massachusetts General Hospital and
lin Definition because of current feasi- from clinical trial, academic, and com- Harvard Medical School, Boston); Niall D. Ferguson,
MD, MSc (Department of Medicine, University Health
bility and lack of data on operational munity sites reflecting practice in the real Network and Mount Sinai Hospital, and Interdepart-
characteristics may become more use- world of clinical research. In addition, we mental Division of Critical Care Medicine, University
ful in the future. We anticipate that clini- evaluated PEEP and CRS as used by cli- of Toronto, Toronto, Ontario, Canada); Ellen Caldwell,
MS (Division of Pulmonary and Critical Care Medi-
cal research using our model of defini- nicians in practice and not as a test of pre- cine, University of Washington, Seattle); Eddy Fan, MD
tion development will be used to revise specified ventilator settings that may be (Department of Medicine, University Health Net-
work and Mount Sinai Hospital, University of To-
the definition in the future. betterthanthevariablesevaluatedherein, ronto, Toronto, Ontario, Canada); Luigi Camporota,
There are limitations to our ap- but may not be practical, particularly in MD (Department of Critical Care, Guy’s and St.
Thomas’ NHS Foundation Trust, King’s Health Part-
proach. First, although the Berlin Defi- observational cohort studies.5,6 ners, London, England); and Arthur S. Slutsky, MD
nition had statistically significantly su- Fifth, because our study was not an (Keenan Research Center of the Li Ka Shing Knowl-
edge Institute of St. Michael’s Hospital; Interdepart-
perior predictive validity for mortality exercise in developing a prognostic mental Division of Critical Care Medicine, University
compared with the modified AECC defi- model for ARDS, we only considered of Toronto, Toronto, Ontario, Canada).
nition, the magnitude of this difference the variables and cutoffs proposed by Author Contributions: Dr Rubenfeld and Ms Caldwell
had full access to all of the data in the study and take
and the absolute values of the AUROC the consensus panel. We could not responsibility for the integrity of the data and the ac-
are small and would be clinically unim- compare this definition directly to the curacy of the data analysis.
Study concept and design: Ranieri, Rubenfeld,
portant if the Berlin Definition was de- AECC definition because the catego- Thompson, Ferguson, Caldwell, Camporota.
signed as a clinical prediction tool. How- ries of that definition overlap. It is pos- Acquisition of data: Ranieri, Rubenfeld, Thompson.
Analysis and interpretation of data: Rubenfeld,
ever, predictive validity for outcome is sible that the outcomes as well as the Thompson, Ferguson, Caldwell, Fan, Slutsky.
only one criterion for evaluating a syn- relative proportion of patients within Drafting of the manuscript: Rubenfeld, Ferguson,
drome definition and the purpose of the each category of ARDS will change if Caldwell, Slutsky.
Critical revision of the manuscript for important in-
Berlin Definition is not a prognostica- the underlying epidemiology of the syn- tellectual content: Ranieri, Rubenfeld, Thompson,
tion tool.33 Although the Berlin Defini- drome evolves due to changes in clini- Ferguson, Caldwell, Fan, Camporota, Slutsky.
Statistical analysis: Rubenfeld, Caldwell, Slutsky.
tion was developed with a framework cal practice or risk factors.34 This is Obtained funding: Ranieri.
including these criteria, we did not em- particularly true for the post hoc higher- Administrative, technical, or material support:
Rubenfeld, Thompson, Fan, Camporota.
pirically evaluate face validity, content risk subset reported, for which the cut Study supervision: Ranieri, Rubenfeld, Thompson,
validity, reliability, feasibility, or suc- points were derived from the data sets. Slutsky.
Conflict of Interest Disclosures: All authors have com-
cess at identifying patients for clinical trial pleted and submitted the ICMJE Form for Disclosure
enrollment. Conclusion of Potential Conflicts of Interest. Dr Ranieri reported
Second, it is possible that our results In conclusion, we developed a consen- receiving consulting fees or honoraria from Maquet
and Hemodec and board membership from Faron. Dr
are not generalizable because of the data sus draft definition for ARDS with an in- Rubenfeld reported receiving consulting fees or hono-
sets we studied. This seems unlikely be- ternational panel using a framework that raria from Ikaria, Faron, and Cerus. Dr Thompson re-
ported receiving support for travel from European So-
cause patients from a broad range of focused on feasibility, reliability, and va- ciety of Intensive Care Medicine; being an advisory
populations, including clinical trials, aca- lidity. We tested that definition using em- board member of Hemodec and AstraZeneca; receiv-
ing consultancy fees from US Biotest, Sirius Genetics,
demic centers, and community pa- pirical data on clinical outcome, radio- sanofi-aventis, Immunetrics, Abbott, and Eli Lilly; and
tients, were included in the analyses. graphic findings, and physiological receiving grants from the National Heart, Lung, and
Third, some variables (eg, CRS and measures from 2 large databases con- Blood Institute. Dr Slutsky reported receiving sup-
port for travel expenses from European Society of In-
PEEP) were missing in some patients in structed from 7 contributing sources to tensive Care Medicine; board membership from Ikaria;
the data sets we used, either due to the assess the predictive value of ancillary receiving consultancy fees from GlaxoSmithKline and
Tarix; having stock/stock options with Apeiron and
mode of mechanical ventilation that pre- variables, refine the draft definition, and Tarix; and sitting on advisory boards for Maquet Medi-
cluded their measurement or the prac- compare the predictive validity of the cal and NovaLung and steering committees for
HemoDec and Eli Lilly. No other authors reported any
ticalities of population-based research. definition to the existing AECC defini- financial disclosures.
However, bias due to cohort selection or tion. This approach for developing the Members of the ARDS Definition Task Force: V. Marco
2532 JAMA, June 20, 2012—Vol 307, No. 23 ©2012 American Medical Association. All rights reserved.
Ranieri, MD (Department of Anesthesia and Inten- Beale, MBBS (Department of Critical Care, Guy’s and ropean Society of Intensive Care Medicine and grant
sive Care Medicine, University of Turin, Turin, Italy); St. Thomas’ NHS Foundation Trust, King’s Health Part- R01HL067939 from the National Institutes of Health
Gordon D. Rubenfeld, MD, MSc (Program in Trauma, ners, London, England); Laurent Brochard, MD (Medi- (Dr Rubenfeld). Dr Ferguson is supported by a Cana-
Emergency, and Critical Care, Sunnybrook Health Sci- cal-Surgical Intensive Care Unit, Hopitaux Universi- dian Institutes of Health Research New Investigator
ences Center and Interdepartmental Division of Criti- taires de Geneve, Geneva, Switzerland); Roy Brower, Award (Ottawa, Canada).
cal Care Medicine, University of Toronto, Toronto, On- MD (Division of Pulmonary and Critical Care Medi- Role of the Sponsors: The European Society of Inten-
tario, Canada); B. Taylor Thompson, MD (Department cine, Johns Hopkins University, Baltimore, Mary- sive Care Medicine, the National Institutes of Health,
of Medicine, Massachusetts General Hospital and Har- land); Andrés Esteban, MD, PhD (Servicio de Cuida- the Canadian Institutes of Health Research, and the en-
vard Medical School, Boston); Niall D. Ferguson, MD, dos Intensivos, Hospital Universitario de Getafe, dorsing professional societies had no role in the design
MSc (Department of Medicine, University Health Net- CIBERES, Madrid, Spain); Luciano Gattinoni, MD (Is- and conduct of the study, in the collection, manage-
work and Mount Sinai Hospital, and Interdepartmen- tituto di Anestesiologia e Rianimazione, Universita de- ment, analysis, and interpretation of the data, or in the
tal Division of Critical Care Medicine, University of To- gli Studi di Milano, Milan, Italy); Andrew Rhodes, MD preparation, review, or approval of the manuscript.
ronto, Toronto, Ontario, Canada); Ellen Caldwell, MS (Department of Intensive Care Medicine, St. George’s Online-Only Material: The eMethods, eReferences,
(Division of Pulmonary and Critical Care Medicine, Uni- Healthcare NHS Trust, London, England); Jean-Louis eTables 1 through 4, and eFigures 1 through 4 are avail-
versity of Washington, Seattle); Eddy Fan, MD (De- Vincent, MD (Department of Intensive Care, Erasme able at http://www.jama.com.
partment of Medicine, University Health Network and University, Brussels, Belgium); Provided data for the Additional Contributions: Salvatore Maggiore, MD,
Mount Sinai Hospital, University of Toronto, Toronto, empiric evaluation of the definition but were not part PhD (Department of Anesthesiology and Intensive Care,
Ontario, Canada); Luigi Camporota, MD (Depart- of the consensus development: Andrew Bersten, MD Agostino Gemelli University Hospital, Università Cattolica
ment of Critical Care, Guy’s and St. Thomas’ NHS (Department of Critical Care Medicine, Flinders Uni- del Sacro Cuore, Rome, Italy), and Anders Larsson, MD,
Foundation Trust, King’s Health Partners, London, En- versity, Adelaide, South Australia); Dale Needham, MD, PhD (Department of Surgical Sciences, Anesthesiol-
gland); and Arthur S. Slutsky, MD (Keenan Research PhD (Outcomes After Critical Illness and Surgery Group ogy and Critical Care Medicine, Uppsala University,
Center of the Li Ka Shing Knowledge Institute of St. [OACIS], Division of Pulmonary and Critical Care Medi- Uppsala, Sweden), attended the roundtable as repre-
Michael’s Hospital; Interdepartmental Division of Criti- cine and Department of Physical Medicine and Re- sentatives of the European Society of Intensive Care
cal Care Medicine, University of Toronto, Toronto, habilitation, Johns Hopkins University, Baltimore, Mary- Medicine. Drs Maggiore and Larsson received no
Ontario, Canada); Massimo Antonelli, MD (Diparti- land); and Antonio Pesenti, MD (Department of compensation for their roles. Karen Pickett, MB BCh
mento di Anestesia e Rianimazione, Universita Cattolica Anesthesia and Critical Care, Ospedale San Gerardo, (Department of Intensive Care, Erasme Hospital, Uni-
del Sacro Cuore, Rome, Italy); Antonio Anzueto, MD Monza, Italy; and Department of Experimental Medi- versité Libre de Bruxelles, Brussels, Belgium), provided
(Department of Pulmonary/Critical Care, University cine, University of Milano Bicocca, Milan, Italy). technical assistance. Dr Pickett received compensa-
of Texas Health Sciences Center, San Antonio); Richard Funding/Support: This work was supported by the Eu- tion for her role in the conference.
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