What is the Berlin definition of Acute Respiratory Distress Syndrome (ARDS)?

Berlin Definition of ARDS

The Berlin Definition, established in 2012, classifies ARDS into three mutually exclusive severity categories based on PaO₂/FiO₂ ratio with minimum PEEP of 5 cmH₂O: mild (200-300 mmHg), moderate (100-200 mmHg), and severe (≤100 mmHg), along with specific criteria for timing, imaging, and origin of edema. 1, 2

Core Diagnostic Criteria

The Berlin Definition requires all four of the following elements to be present 1, 2:

Timing

• Respiratory symptoms must develop or worsen within 1 week of a known clinical insult or new/worsening respiratory symptoms 3, 1

Chest Imaging

• Bilateral opacities must be present on chest radiograph or CT scan 1
• These opacities cannot be fully explained by pleural effusions, lobar/lung collapse, or nodules 3, 2
• A reference set of chest radiographs has been developed to enhance inter-observer reliability 2

Origin of Edema

• Respiratory failure cannot be fully explained by cardiac failure or fluid overload 3, 1
• If no ARDS risk factor is apparent, objective assessment (such as echocardiography) is required to exclude hydrostatic pulmonary edema 3, 2
• The pulmonary artery wedge pressure criterion from the prior definition was removed 2

Oxygenation (Severity Classification)

The severity categories require measurement on minimum PEEP of 5 cmH₂O 4, 1:

• Mild ARDS: PaO₂/FiO₂ 200-300 mmHg with PEEP or CPAP ≥5 cmH₂O 3, 4, 1
• Moderate ARDS: PaO₂/FiO₂ 100-200 mmHg with PEEP ≥5 cmH₂O 3, 4, 1
• Severe ARDS: PaO₂/FiO₂ ≤100 mmHg with PEEP ≥10 cmH₂O 3, 4, 1

Validation and Performance

The Berlin Definition demonstrates superior predictive validity compared to the prior American-European Consensus Conference (AECC) definition 1, 2:

• Mortality increases with severity: mild 27%, moderate 32%, severe 45% (P < .001) 1
• Duration of mechanical ventilation in survivors also increases: mild 5 days (IQR 2-11), moderate 7 days (IQR 4-14), severe 9 days (IQR 5-17) (P < .001) 1
• Area under receiver operating curve for mortality: 0.577 vs 0.536 for AECC definition (P < .001) 1

Key Improvements Over Prior Definition

The Berlin Definition addressed several limitations 5, 2:

• Removed the term "acute lung injury" (ALI), which is now reserved for general description or animal models 6
• Eliminated the pulmonary artery wedge pressure requirement, which was impractical 2
• Added minimum PEEP requirements to standardize oxygenation measurements 4, 1
• Created three mutually exclusive severity categories rather than two 1
• Developed reference materials and vignettes to improve reliability 2

Common Pitfalls and Clinical Application

Critical measurement requirement: The PaO₂/FiO₂ ratio must be calculated with patients on at least 5 cmH₂O of PEEP to ensure accurate classification 4, 1

Misattribution of pulmonary edema remains a significant challenge, as clinician interpretation of the origin of edema and chest radiograph criteria may be less reliable 4, 5. When no clear ARDS risk factor exists, objective cardiac assessment is mandatory 2.

Underrecognition in clinical practice: Despite the improved definition, ARDS remains underrecognized by clinicians, and evidence-based interventions are underused 3, 5. The Berlin Definition was specifically designed to enhance case recognition in both research and clinical settings 2.

Treatment Implications by Severity

The severity classification directly guides therapeutic interventions 3, 4:

• Severe ARDS (PaO₂/FiO₂ ≤100 mmHg): Strong recommendation for prone positioning >12 hours/day 3, 4
• Moderate to severe ARDS: Conditional recommendation for higher PEEP strategies 3
• All ARDS: Lung-protective ventilation with tidal volumes 4-8 ml/kg predicted body weight and plateau pressure ≤30 cmH₂O 3

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New Global Definition of ARDS

As of the available evidence through 2025, there is no formally adopted "New Global Definition" that has replaced the Berlin Definition. 4, 1 The Berlin Definition from 2012 remains the current international standard endorsed by the European Society of Intensive Care Medicine, American Thoracic Society, and Society of Critical Care Medicine 3, 1, 2.

Ongoing Evolution and Refinements

While the Berlin Definition remains the standard, ongoing research continues to identify 7, 5:

• Biologic subphenotypes using plasma biomarkers, genetics, and latent class analysis 7
• Radiographic phenotypes based on diffuse versus focal patterns of infiltrates 7
• Direct versus indirect lung injury subtypes that may respond differently to treatment 6, 7

These refinements represent the future direction toward precision medicine in ARDS rather than a replacement definition 7.