Exploring the Berlin Definition of Ards

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EXPLORING THE BERLINDEFINITION OF ARDS

Niall D. Ferguson, MD, FRCPC, MScInterim Director, Critical Care Medicine

University Health Network & Mount Sinai Hospital

Associate Professor of Medicine & Physiology

Interdepartmental Division of Critical Care MedicineUniversity of Toronto


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jamanetwork.comCopyright restrictions apply.

Available at www.jama.com

The ARDS Definition Task Force

Acute Respiratory Distress Syndrome:The Berlin Definition

Published online May 21, 2012

An initiative of

Endorsed by


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Why Do We Need anARDS Defintion AT ALL?


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Reliable and Valid Definitions are

ESSENTIAL to Conduct andInterpret Clinical Research


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Importance to Researchers

Enable epidemiological studies

Facilitate enrolment into clinical trials

Allow comparison between studies

Enhance linkages between clinical and basic science Phenotype Genotype relationship


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Importance to Clinicians

Ability to implement results of positive RCTs in clinical

practice

Lower Vt for ALI

May also be useful in prognostic discussions with

patients/families


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Importance to Administrators

Epidemiological studies need definitions

These in turn may be useful in planning resource allocation


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The American-European Consensus

Conference on ARDSBernard et al. AJRCCM1994; 149:818-24

American-European Consensus (AECC)

PaO2/FIO2 200 * &

Acute onset &

CXR with bilateral infiltrates &

PAWP 18

*Regardless of PEEP level

or no clinical evidence of left atrial hypertension


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Sensibility Concerns - AECC

No definition of acute

Risk factors not included

Inconsistency of PaO2/FIO2 ratio

Effect of PEEP Effect of FIO2

PCWP & ARDS can coexist

Interpretation of the CXR has poor reliability

Crit Care Med 2008; 36:2912-2921


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Effects of Airway Pressure

PAW = 22 PaO2/FIO2 = 80 PAW = 30 PaO2/FIO2 = 281


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AECC Sensibility Concerns

No definition of acute

Appropriate clinical setting not formally

included

Inconsistency of PaO2/FIO2 ratio

effect of PEEP

effect of FIO2

PCWP and ARDS can coexist CXR interpretation has poor reliability


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26

Median PAWP (mm Hg)

% of

patients

with PA

catheters

Data from Stewart et al. NEJM1998 338:335-61


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29% had PAOP > 18

97% of these had N or

elevated CI


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Interobserver variability in

applying a radiographic

definition of ARDSRubenfeld et al. Chest1999 116:1347-53


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Interobserver variability in applying a radiographic

definition of ARDSRubenfeldet al. Chest1999 116:1347-53

21 clinical researchers and opinion leaders

28 CXRs from hypoxemic ICU patients

= 0.55 ( 0.02) for inter-observer agreement

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Interobserver variation in interpreting chest

radiographs for the diagnosis of ARDSMeade et al.AJRCCM 2000 161:85-90

Intensivists and radiologists reading 778 CXRs fromPLVS study

= 0.38 to 0.55 for inter-observer agreement = 0.72 to 0.88 for inter-observer agreement after training


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The importance of recognising ALI


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From Ware & Matthay NEJM 2000


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Importance of Specificity in RCTs

Other Diseases

Specific TestNon-Specific Test


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Process

Appointment of Chairs

Selection of Panelists

Presentations & consensus discussions

Sept 30 Oct 1 2011, Berlin, Germany

Empiric evaluation of draft definition

Focus on feasibility, reliability, validity

Consensus revisions

Society endorsements

Evaluation of Berlin Definition


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Conceptual Model of ARDS

Panelists agreed that ARDS is:

A type of acute, diffuse, inflammatory lung injury Leading to increased pulmonary vascular permeability, increased

lung weight, loss of aerated lung tissue

Clinical hallmarks are hypoxemia, bilateral opacities, shunt, dead

space, decreased compliance

Morphologically DAD

Evolutionary not Revolutionary change

Maintain links to AECC definiton


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Berlin Draft Definition

Acute Respiratory Distress SyndromeTiming Within 1 week of a known clinical insult or new/worsening respiratory symptoms

Origin of EdemaRespiratory failure not fully explained by cardiac failure or fluid overload;

Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present

Mild Moderate Severe

Oxygenation b200


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Novel patient-level meta-analysis of 7 cohorts:

4 Clinical and 3 Physiological

Physiological Cohort

269 Patients

Clinical Cohort

4188 Patients


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Demographics of ARDS Clinical Cohort

2 population based cohorts

1 clinical trials cohort

1 academic hospitals cohort

N=4188Sites 56-79Years enrolled 1996-2007

Age (mean) 54.5Gender (% male) 57%Primary Risk Factor

Pulmonary Sepsis 35%Other Sepsis 34%

Trauma 7%

Other/None 24%PaO2/FiO2ratio mean 150PaO2/FiO2< 200 76%CXR with > 3quadrants

73%

Mortality 34%


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Evaluation Process - Analytic Framework

Evaluate the value of proposed ancillary variablesin defining the Severe ARDS subgroup in thedraft definition

Determine the distribution of patientcharacteristics across definition severitycategories

Determine the predictive validity for mortality of

the final Berlin Definition Compare the final Berlin definition to the AECCdefinition


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Evaluation of SevereAncillary variables identify a smaller group of patients with similar mortality

Draft ARDSPaO2/FiO2 < 100 mmHg

PEEP > 10 cm H2O

3 or 4 quadrant opacities on CXR

Crs < 40 ml/cm H2O

VeCorr > 10 L/min

Final ARDSPaO2/FiO2 < 100 mmHg

PEEP > 5 cm H2O

Bilateral opacities on CXR

45% Mortality

Moderate

64%

Mild

22%

Severe

14%

Mild

22%

Moderate

50%

Severe

28%

Mortality

45%


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Berlin Definition of ARDS


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Distribution of patients across categories

of ARDS

ARDS3670

Mild

Moderate

Severe

27%

Mortality

45%

Mortality

22%

50%

28%

32%

Mortality


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Predictive validity of Berlin Definition - Clinical

0

10

20

30

40

50

Mild Moderate Severe0

10

20

30


Mortality % Ventilator Free Daysmedian

0

5

10

15

20

25

30


Ventilator days survivorsmedian

P


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Predictive validity of Berlin Definition - Physiologic


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Conclusions

First study to combine consenus and evaluation of a critical

illness syndrome definition in a single iterative process

Berlin Definition addresses some of the limitations of the

AECC Definition for ARDS Provides training set of CXRs and Clinical Vignettes

Without evaluation a more complex definition that identified a

smaller subset of Severe ARDS patients would have been

adopted

Future modifications to critical illness syndrome definitions

should be guided by a process that combines empiric

evaluation with expert consensus


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Berlin Definition Limitations and Future

Directions

Predictive validity only one criterion for revised definition

While PEEP, compliance, chest radiograph, and dead space do notadd to predictive validity of Severe ARDS definition, they are importantvariables for clinicians to measure and understand in ARDS

Many variables and measures of interest (EVLW, Biomarkers, CT) notincluded in definition primarily due to feasibility concerns and lack ofdata on validity

Mechanistic variables may be included for study specific researchquestions (recruitability, inflammatory markers)

Other aspects of validity and reliability not empirically measured Anticipate further work to evaluate and improve the Berlin Definition


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The ARDS Definition Task Force

ChairsMarco Ranieri

Gordon Rubenfeld

Taylor Thompson

Data or statistical supportEllen Caldwell

Andrew Bersten

Dale Needham

Antonio Pesenti

Additional attendees

Salvatore Maggiore

Agostino GemelliAnders Larsson

Karen Pickett

MembersMassimo Antonelli

Antonio Anzueto

Richard Beale

Laurent BrochardRoy Brower

Luigi Camporota

Andrs Esteban

Eddy Fan

Niall D Ferguson

Luciano Gattinoni

Andrew Rhodes

Arthur S. Slutsky

Jean-Louis Vincent


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[email protected]

October 28-31, 2012Sheraton Centre Hotel, Toronto

Documents

Exploring the Berlin Definition of Ards