Acute Respiratory Distres Syndrom

(ARDS). The “Berlin Definition”

Marko Ranieri
 Background
• The first definition of acute respiratory distress syndrome
(ARDS) dates to Ashbaugh (1967): 12 patients with
severe hypoxemia that was refractory to supplemental
oxygen, but which in some cases was resposive to PEEP;
autopsies showed widespread inflamation, edema, and
hyaline membranes.
• Over the next 25 years several different definitions were
proposed with varying diagnostic criteria.
• In 1994 broad consensus was achived with publication of
the American-European Consensus Conference (AECC)
 AECC
Timing Oxygenation Chest Pulmonary
Radiograph Artery Wedge
pressure
ALI Acute ≤ 300 Bilateral ≤ 18 mmHg/no
onset (regardless of infiltrates evidence of left
PEEP) atrial
hypertension
ARDS Acute ≤ 200 Bilateral ≤ 18 mmHg or
onset regardless of infiltrates no evidence of
PEEP left atrial
hypertension
 Background
• This definition was widely adopted by clinical
researchers and clinicians and a large amount of
data about ARDS has been generated
subsequently.
• The AEEC definition has clearly advanced our
knowledge of ARDS and improved our ability to
better care for these patients.
• All definitions, however, need to be reviewed
and adjusted periodically to reflect new
information and experience gained since their
creation, and the AECC definition of ARDS is no
exception to this rule.
 CRITICISM of AECC:
HYPOXEMIA
• PaO2/FiO2 is not constant across a range of FiO2
and may vary in response to ventilator settings,
particulary PEEP

Gowda 1997, Ferguson 2004, Villar 1999, Villar 2007.

CRITICISM of AECC:
CHEST X-RAY
• Inter – observer reliability is only moderate
even when applied by experts

Rubenfeld 1999, Meade 2000

CRITICISM of AECC:
WEDGE PRESSURE
• Patients with ARDS may have an elevated
PAWP (when measured); often because of
transmitted airway pressure and/or vigorous
fluid resuscitation

Ferguson 2002, ARDSNet 2006

CRITICISM of AECC:
SENSITIVITY and SPECIFICITY
• When AECC criteria are compared with DAD:
sensitivity is 84% specificity is 51%

Esteban 2004,Ferguson 2005

CRITICISM of AECC:
PERCEPTION of ALI AS NOT SEVERE AS ARDS

• ARDS is under – recognized by clinicians as

defined using the AECC criteria.
This appears to be particularly true for ALI (P/F <
300)

Ferguson 2005, Kalhan:2006, Rubenfeld:2004

 METHODS
• ESICM convened an international panel of
experts, with representation of ATS
• The objectives were to update the ARDS
definition using a systematic analysis of:
– current epidemiologic evidence
– physiological concepts
– results of clinical trials
 ARDS Taskforce Members
• Chair Persons: V. Marco Ranieri, Gordon D.
Rubenfeld, B. Taylor Thompson
• Europe: M. Antonelli, R. Beale, L. Brochard, L.
Gattinoni, A. Esteban, JL Vincent, A. Rhodes.
• US/Canada: A. Anzueto, R. Brower, N.
Fergusson, A. Slutsky
 ARDS Taskforce Members
• Writing Committee
Edyy Fan, Luigi Camporota, Karen Picket
• ESICM Representatives
Giorgio Conti, Andres Larsson, Rino Maggiore,
Rui Moreno
• ATS Representative
Gordon D. Rubenfeld
 METHODS
• All modifications were based on the principle that
syndrome definitions must fulfill three criteria:
– feasibility
– reliability
– validity

Rubenfeld: 2003
 FEASIBILITY
• Definitions should rely on diagnostic tests that
can routinely used by CLINICIANS to identify
patients for appropriate treatments and by
CLINICAL SCIENTISTS to facilitate clinical trial
enrolment.

Rubenfeld: 2003
Variables that were included in the definition
since were feasible
• Timing
• Hypoxemia
• Origin of Edema
• Radiological Abnormalities
• Additional Physiological Derangement
 RELIABILITY
• It is essential for researchers to identify the same
patients across studies and for clinicians to apply
therapies to the patient that benefits the most
with the least risks definitions must be reliable as
measured by inter-observer agreement:

use training set of Chest X – Rays

 VALIDITY
• Is commonly evaluated as sensitivity and
specificity in reference to a gold standard

• However, ARDS as many syndromes in medicine

(COPD, depression, sepsis) does not have a gold
standard to reference
 VALIDITY
• The validity of definitions of syndromes that
do not have reference standards may rely on
indirect techniques like face, construct,
predictive and concurrent validity
VALIDITY MEASURE EXPLANTATION
FACE VALIDITY Definition appears “on its
face” to represent the disease
CONTENT VALIDITY Definition contains all of the
elements relevant to the
disease
CRITERION VALIDITY Definition corresponds to a
gold standard
PREDICTIVE VALIDITY Definition is able to predict
something it theoretically
should be able to predict
CONCURRENT VALIDITY Definition is able to
distinguish between groups
that it theoretically should be
able to distinguish between
In ARDS
Patients identified by the
proposed definition “feel right”
to clinicians
Proposed diagnostic criteria
contain all of the elements
deemed essential to the
diagnosis of ALI, usually as
assessed experts.
Diagnostic criteria for ALI
correspond to a gold standard
Diagnostic criteria predict some
outcome that is unique to ALI
(e.g, mortality, or response to
therapy)
Diagnostic criteria distinguish
ALI from other forms of acute
hypoxemic respiratory failure
 Face validity
formalization in a “conceptual model” of
how clinicians recognize patients with the
syndrome
 The conceptual model of ARDS
1. ARDS is a type of acute diffuse lung injury
associated with recognized risk factors,
characterized by inflammation leading to
increased pulmonary vascular permeability
and loss of aerated lung tissue.

2. The hallmarks of the clinical syndrome are

hypoxemia and bilateral radiographic
opacities (standard chest x-ray or CT scan)
 The conceptual model of ARDS
3. ARDS is associated with recognized risk factors
and is characterized by inflammation leading to
increased pulmonary vascular permeability and
loss of aerated lung tissue.
4. Physiological derangements include increased
pulmonary venous admixture, increased
physiological dead-space, decreased respiratory
system compliance.
5. Morphological hallmarks are lung edema,
inflammation (i.e., diffuse alveolar damage)
 Common Risk Factor for ARDS
• Direct
o Pneumonia
o Aspiration of gastric contents
o Inhalation injury
o Pulmonary contusion
o Near drowning
 Common Risk Factor for ARDS
•Therapy directed at each underlying cause is high priority
.However – the physiological abnormalities overlap to such a degree that this classification
does not allow for selection of supportive therapy for an individual patient

• Direct • Indirect
o Pneumonia o Non pulmonary sepsis
o Aspiration of gastric
o Major trauma
contents
o Inhalation injury o Multiple transfusions
o Pulmonary contusion o Severe burns
o Near drowning o Pancreatitis
o Non – cardiogenic shock
o Drug overdose
 ARDS
Mild Moderate Severe
Timing Acute onset within 1 week of a known clinical insult or new/worsening
Hypoxemia respiratory
PaO /FiO 201 symptoms
– 300 PaO /FiO ≤200 PaO /FiO ≤100
2 2 2 2 2 2
with PEEP/CPAP with PEEP/CPAP with PEEP/CPAP
5 5 5
Origin of Edema
Respiratory failure not fully explained by cardiac failure or fluid overload**
Radiological Bilateral opacities * Bilateral opacities* Opacities involving
Abnormalities at least 3
quadrants*
Additional N/A N/A VE corr > 10 L/min
Physiological or
Derangement CRS < 40 ml/cm H2O

*Not fully explained by effusions, nodules, masses, or lobar/lung collapse; use training set of CXRs

**Need objectives assessment if no risk factor present (See table)

VE corr= VE x PaCO2/40 (corrected for Body Surface Area)
 “Berlin definition” of ARDS
• Does it fit the
“face and
“predictive”
validity” criteria
 The “Berlin definition” in:
Ospedale Maggiore, Milano: Luciano Gattinoni
Mild (23%) Moderate (63%) Severe (14%)
PaO2/FiO2 246±41 146±29 75±16 P< 0.0001
Lung weight (mg) 1299±274 1458±503 1905±598 P< 0.0001
Recrutability (%) 7±7 13±10 23±12 P< 0.0001
Not inflated 0.30±14 0.39±0.14 0.51±0.17 P< 0.0001
tissue (%)
Compliance 43±14 39±13 36±16 P=0.23
Corrected VE (L) 9.8±2.3 10.2±3.7 12.8±2.3 P< 0.01
Shunt (%) 8±1 19±1 40±2 P< 0.0001
Mortality (%) 10 32 62