Acute Respiratory Distress
Syndrome: The Berlin Criteria An
Update On Clinical Guidelines
DAVID AYMOND, MD
ARDS History
 The first definition of ARDS dates to Ashbaugh and
colleagues in 1967 when they described 12 patients
with severe acute respiratory failure. They noticed
the pts had severe hypoxemia that was refractory to
supplemental oxygen, but which in some cases was
responsive to the application of PEEP. At autopsy
they observed widespread pulmonary inflammation,
edema, and hyaline membranes.
 In 1994 the American-European Consensus
Conference (AECC) defined ARDS. They redifined in
2000.
The ARDS Conceptual Model: Path0physiology
Defined by Clinicians
 Face validity derives from an understanding of how we recognize
the syndrome, therefore, considerable discussion at the Berlin
consensus focused on developing a conceptual model of ARDS
 The panel agreed that ARDS is a type of acute diffuse lung injury
associated with a predisposing risk factor, characterized by
inflammation leading to increased pulmonary vascular permeability
and loss of aerated lung tissue. The hallmarks of the clinical
syndrome are hypoxemia and bilateral radiographic opacities (using
stnadard CXR or CT scan), associated with several physiological
derangements including: increased pulmonary venous admixture
(intra-pulmonary shunt), increased physiological dead space, and
decreased respiratory system compliance [Vt/(PP-PEEP)]
 Morphological hallmarks in the acute phase are lung edema,
inflammation, hyaline membranes, and alveolar hemmorhage (i.e.
diffuse alveolar hemorrhage=DAD)
AECC Definition
 American-Euro Consensus Conference (AECC)
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In an appropriate clinical setting (i.e. a likely underlying cause)
There is an acute onset (< 72hrs) of bilateral alveolar and/or
interstitial infiltrates on frontal chest radiograph
A ratio of the Pa02 divided by the Fi02 < 300 (ALI) or < 200
(ARDS)
Non-cardiogenic pulmonary edema = PCWP < 18 or no clinical
evidence of increased LAP
Why Was An Update Needed?
 AECC Pitfalls:
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Hypoxia defined as PaO2/FiO2 ratio. This is a problem because the
FiO2 varies depending on the PEEP (Gowda 1997, Ferguson 2004)
Wedge Pressure: Patients with ARDS may have elevated PAWP b/c
of transmitted airway pressure and /or vigourous fluid resuscitation
(ARDSnet 2006)
CXR criterion has only moderate inter-observer reliability even when
applied by experts
Definition has a sensitivity of 84% but a specificity of only 51%. This
was shown by autopsy of patients with lung biopsy.
ALI is under-recognized by clinicians, especially those with very
minor ALI
The AECC definition says the onset of respiratory failure should be
acute, but doesn’t define a time
ARDS-Defined
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Berlin Criteria
Timing: Within 1 week of a known clinical insult or new or
worsening respiratory symptoms
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Chest Imaging: Bilateral opacities on x-ray or CT scan not fully
explained by effusions, lobar/lung collapse, or nodules
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Origin of Edema: Respiratory failure not fully explained by cardiac
failure or fluid overload. Need objective assessment (Echo and
CVP) to exclude hydrostatic edema if no risk factor for ARDS
present
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Oxygenation:
Mild: Pa02/Fi02 of 201-300 mmHg with PEEP/CPAP >5 cm H2O
(27%)
Moderate: PaO2/FiO2 of 101-200 with PEEP > 5 cm H2O (32%)
Severe: PaO2/FiO2 < 100 with PEEP > 5 cm H2O (45%)
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ARDS-Defined (cont)
 Berlin Criteria: 4 ancillary variables were included
to help define severe ARDS
1.
2.
3.
4.
Radiographic severity
Respiratory System Static Compliance (Vt/Pplat-PEEP)
PEEP >10
Corrected Expired Volume per Minute > 10L/min
Results From Comparison of AECC and ARDS
Definitions (JAMA.2012;307 (23): 5669)
 Meta-analysis of 4188 patients with ARDS from 4 multicenter
clinical data sets and 269 patients with ARDS form 3 singlecenter data sets.
 This meta-analysis found, when compared with the AECC
definition, the final Berlin Definition predicted duration of
mechanical ventilation based on degree of hypoxemia, percent
of shunt, and had better predictive validity for mortality.
*The 4 variables were excluded from the definition of Severe
ARDS after the meta-analysis found that they did not
improve the predictive value for mortality
Authors did a post-hoc “high risk profile” of patients with a 52%
mortality from ARDS. These patients had severe ARDS and
either a static compliance of < 20 cm H2O or a corrected
expired volume of > 13 L/min
What is the Origin of Edema Mean in the New
Berlin Definition?
 The panel recognized that hydrostatic edema (Cardiogenic) is
one of the most common alternative diagnoses in patients
presenting with ARDS. However, given the declining use of
Pulmonary Artery Catheters worldwide and the recognition
that hydrostatic edema and ARDS may coexist, the pulmonary
artery wedge pressure criterion was removed. The panel
therefore decided that patients whose respiratory failure is not
fully explained by cardiac failure or fluid overload as judged
by the treating physician using all available data may qualify
as having ARDS. Nevertheless, if no known etiologic RF for
ARDS is apparent, objective evaluation of cardiac function is
required to help R/O hydrostatic edema secondary to CHF.
 What did they define as established risk factors for ARDS?
Known Etiologic Risk Factors
Direct Causes
Pneumonia (~40%)
Aspiration (~15%)
Near Drowning
Inhalation Injury
Lung Contusion
Indirect Causes
Sepsis (~25%)
Traumatic Shock
Non Cardiogenic Shock
DIC
Pancreatitis
TRALI
Drug OD
Severe Burns
Pulmonary Vasculitis
Treatment
 Ventilation
 Primary goal is to prevent damage to undamaged alveoli
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The 4 potential mechanisms of alveolar damage in pts with ARDS:
1.
Barotrauma: pressure
2.
Volutrauma: over-distention of alveoli from high Vt ventilation
3.
Atelectrauma: shearing force on alveoli from opening during inspiration
and collapse on expiration
4.
Biotrauma: pro-inflammatory cytokines releases from excessive
mechanical forces on the lung
In 2000, the ARDS network was established and they did a study that
showed improvement in mortality (9%) with lung protective ventilation,
spp. Lower Vt of < 6cc/kg of IBW and plateau pressure limits of 30 cm
H2O
Therefore current guidelines say to maintain low tidal volume ventilation
< 6 mL/kg of IBW and to maintain Plateau Pressures < 30 cm H20;
what variables affect plateau pressure? What is a plateau pressure?
Ventilator Treatment (Cont)
 Current Guidelines are as follows (ARDS network)
 Vt < 6 mL/kg of IBW (keep pH > 7.15)
 Pplat < 30 cm H2O
 PEEP: titrate to a P plat of 28-30 cm H2O  dec time on vent,
better lung mechanics, and dec in mortality; if able to increase
PEEP w/o inc Pplat suggests alveolar recruitability
 FiO2: increase PEEP rather than FiO2 (keep <0.6)
 I:E ratio goal: Duration of inspiration be < duration of
expiration
 Set initial rate to approximate baseline minute ventilation (not
more than 35 bpm)
 Adjust Vt and RR to achieve pressure goals and pH
Treatment Details-Tidal Volume and pH
 Permissive Hypercapnia
 This is a term that was coined when low Vt started being used b/c the
low Vt leads to respiratory acidosis from accumulating CO2
 just consider the definition of minute ventilation= RR x Vt this is
indirectly related to CO2, meaning if you increase either variable, CO2
goes down and vice versa.
 Current guidelines therefore suggest keeping pH > 7.15 and PaCO2 in the
45-55 mm HG range
 ARDS network set forth the following guidelines:
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pH Goal: 7.30-7.45
Acidosis management: pH < 7.3
 f pH 7.15-7.30: increase RR until pH > 7.30 or PaCO2 < 25 (max set RR 35)
 If pH < 7.15: Increase RR to 35
• If pH remains < 7.15, Vt may be increased in 1 ml/kg steps until pH > 7.15 (Pplat
target of 30 may be exceeded); consider giving NaHCO3
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Alkalosis management: ph > 7.45: decrease vent rate if possible
Treatment Details- Pplat
 Plateau pressure is the pressure that is applied to small
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airways and the alveoli
Factors that contribute to the Pplat are Vt, PEEP, static
compliance, and PS
Is measured at the end of inspiration (inspiratory hold)
Different from the peak pressures; peak pressures are the
maximal pressures in the proximal airways at the end of each
lung inflation.
Pressure Support: at the onset of each spp breath, the negative
pressure generated by the patient opens a valve that delivers
the inspired gas at a pre-selected pressure (usually 5-10 cm
H2O). The majority of this pressure is distributed at the
proximal airway (trachea, main-stem bronchus)
Treatment Details: PEEP
 PEEP
 PEEP helps recruit atelectatic lung tissue and prevents the
development of further atelectasis; it thereby improves
ventilation to perfusion matching. This is the same thing as
decreasing the intra-pulmonary shunt
 Current guidelines suggest using PEEP to maintain
oxygenation instead of FiO2, suggest to never go above 0.6 on
FiO2, with the goal of getting FiO2 below 0.5 ASAP
Supportive Therapy
 Paralysis
 Not currently recommended, although a study showed that if
cisatracurium was started early in ARDS and only used for 48
hrs there was a decrease in mortality. This was due to the
ability to provide better lung protective ventilation
 Nutrition
 Tube feeds with increased fat and decreased carbs should lead
to less CO2 production and result in a decreased amount of
respiratory acidosis.
*Fluid management discussed on last slide
ARDS Treatment (cont)
Steroids:
 1 - 7 days but ideally < 72 hrs:
 Methylprednisolone 1mg/kg IV bolus then 1mg/kg/day
continuous IV infusion for 14 days;
 After 14 days decrease to 0.5mg/kg/day x 7 days, then
0.25mg/kg/day IV x 7 days, then stop
 If no clear physiologic or radiologic improvement in 3-5
days, d/c
 7 - 14 days, if steroids not started earlier, benefit less
certain, still try above protocol and if no benefit in 3-5
days d/c
 > 14 days, not recommended and may cause inc
mortality
Rescue Therapy
 Therapies that are not well proven but used for patients in
extreme situations not responding to aforementioned therapy
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Alternative Vent modes:
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Positioning
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APRV: Airway pressure release ventilation maintains a constant airway
pressure, recruiting more alveoli; no survival advantage
HFO : ? Useful for pts who have severe hypoxemia and failed conventional
vent
ECMO: studies ongoing (currently no proven benefit in adults)
Oxygenation improves in 2/3 of pts when placed in prone position by
unloading weight of the heart and improved aeration of dorsal lung regions
Recruitment Maneuvers
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A typical recruitment maneuver is an attempt at re-expanding atelectatic lung
tissue by applying a constant positive pressure of 30-40 cm H2O for ~ 60
seconds; ROUTINE USE NOT SUPPORTED
Outcomes
 Survival rates for ALI/ARDS are controversial. Some evidence
suggests improved survival while a recent estimate of survival in the
control groups of studies in ALI suggest that survival rates are
unchanged (Am J Respir Crit Care Med. 2009; 179:220)
 Most pts that survive have abnl on PFT including muscle weakness,
les distance walked in the standardized 6 min walk test, and in one
study 6% had O2 saturation less than 88% with exercise
 A most recent study has found that 5 yrs after surviving ARDS the
survivors had normal to near-normal results on their PFT, but they
had significant exercise limitation with a decreased physical quality
of life. As expected younger pats had a greater rate of recovery than
older ones, but neither group returned to normal predicted levels of
physical function at 5 yrs (N Engl J Med. 2011; 364:1293)
Fluid Management in ARDS
 Target CVP 4-6 cm H20 (if nonoliguric and
normotensive)
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This increases vent and ICU free days, but no effect on
mortality (ARDS network FACTT trial)
Accomplished with fluid bolus and furosemide bolus/infusion
(20mg or 3mg/hr)
 Non-Oliguric = UOP > 0.5 cc/kg/hr