What is the globally accepted definition of acute respiratory distress syndrome (ARDS)?

ARDS Global Definition

The globally accepted definition of ARDS is the Berlin Definition (2012), which requires four key criteria: acute onset within one week of a known clinical insult, bilateral opacities on chest imaging not fully explained by effusions or nodules, respiratory failure not fully explained by cardiac failure or fluid overload, and impaired oxygenation measured by PaO₂/FiO₂ ratio with minimum PEEP of 5 cmH₂O. 1

Core Diagnostic Criteria

The Berlin Definition establishes ARDS diagnosis through the following mandatory components:

• Timing: Acute onset within 1 week of a known clinical insult or new/worsening respiratory symptoms 2, 1, 3
• Imaging: Bilateral pulmonary opacities on chest radiography or CT scan that cannot be fully explained by effusions, lobar/lung collapse, or nodules 2, 1, 3
• Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload; if no clear ARDS risk factor exists, objective assessment (e.g., echocardiography) is needed to exclude hydrostatic edema 1, 3
• Oxygenation impairment: Measured by PaO₂/FiO₂ ratio with minimum PEEP of 5 cmH₂O 1, 4

Severity Classification

The Berlin Definition categorizes ARDS into three mutually exclusive severity levels based on degree of hypoxemia (all measured with PEEP ≥5 cmH₂O):

• Mild ARDS: 200 mmHg < PaO₂/FiO₂ ≤ 300 mmHg (mortality ~27%) 1, 4
• Moderate ARDS: 100 mmHg < PaO₂/FiO₂ ≤ 200 mmHg (mortality ~32%) 1, 4
• Severe ARDS: PaO₂/FiO₂ ≤ 100 mmHg (mortality ~45%) 1, 4

These severity categories demonstrate strong predictive validity for mortality and duration of mechanical ventilation, with progressive worsening across categories 1.

Pathophysiological Basis

ARDS is characterized by specific pathological features that distinguish it as a clinical syndrome:

• Leukocyte infiltration, local immune activation, and alveolar endothelial and epithelial injury with increased pulmonary vascular permeability 2
• Acute pulmonary edema and loss of aerated lung tissue 2
• Diffuse alveolar damage evolving through exudative, fibroproliferative, and fibrotic phases with hyaline membrane formation 5
• Surfactant depletion, extensive intrapulmonary shunting, and profound hypoxemia 6

Evolution from Prior Definitions

The Berlin Definition (2012) addressed critical limitations of the 1994 American-European Consensus Conference (AECC) definition:

• Improved predictive validity: The Berlin Definition demonstrates significantly better predictive validity for mortality (AUC 0.577 vs 0.536, p<0.001) compared to the AECC definition 1
• Eliminated "Acute Lung Injury" term: Removed the separate ALI category to reduce confusion 1, 4
• Clarified timing: Specified "within 1 week" rather than vague "acute" onset 1, 7
• Added PEEP requirement: Mandated minimum 5 cmH₂O PEEP for oxygenation assessment to standardize measurements 1, 7
• Expanded ventilation modes: Included patients on non-invasive ventilation 7

Critical Diagnostic Pitfalls

When applying the Berlin Definition, clinicians must avoid several common errors:

• Misclassification of severity: Always calculate PaO₂/FiO₂ ratio with patients on at least 5 cmH₂O PEEP; failure to do so leads to inaccurate severity staging 8
• Inadequate exclusion of cardiogenic causes: Cardiac failure must be actively ruled out through clinical assessment and echocardiography when no clear ARDS risk factor exists 8, 3
• Reliability issues: Clinician interpretation of chest radiograph findings and origin of edema shows variable reliability, potentially contributing to underrecognition of ARDS 4
• Mimicking conditions: Diffuse interstitial lung diseases, diffuse pulmonary infections, and drug-induced lung injury can present identically and require specific alternative treatments 8

Inherent Heterogeneity

Despite standardized diagnostic criteria, ARDS demonstrates substantial heterogeneity that impacts treatment response:

• No specific aetiological, physiological, or biological criteria are required for diagnosis, resulting in variation across three distinct levels: aetiological, physiological, and biological 2
• This heterogeneity has contributed to decades of failed therapeutic trials, as treatments targeting specific pathophysiological mechanisms may only benefit certain subgroups 2
• In-hospital mortality remains 30-40% despite the refined definition 2