What is the current worldwide definition of acute respiratory distress syndrome (ARDS) as of 2023?

Global Definition of ARDS 2023

The 2023 global definition of ARDS expands diagnostic criteria beyond the Berlin definition by broadening chest imaging modalities, incorporating alternative hypoxemia assessment methods, and adding criteria for resource-limited settings, though this expansion may increase false-positive diagnoses. 1

Core Diagnostic Criteria (Maintained from Berlin Definition)

The fundamental diagnostic framework remains anchored in four key elements:

• Timing: Acute respiratory symptoms must develop within 1 week of a known clinical insult or present as new/worsening respiratory symptoms 2, 3

• Imaging: Bilateral pulmonary opacities on chest radiograph or CT scan that cannot be fully explained by pleural effusions, lobar/lung collapse, or nodules 2, 4

• Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload; when no clear ARDS risk factor exists, objective assessment (echocardiography) is required to exclude hydrostatic pulmonary edema 2, 3

• Oxygenation impairment: The PaO₂/FiO₂ ratio must be measured with the patient receiving at least 5 cmH₂O of positive end-expiratory pressure 5, 2

Severity Stratification

ARDS severity remains classified into three mutually exclusive categories based on degree of hypoxemia:

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

Key Expansions in the 2023 Definition

The 2023 global definition introduces several important modifications:

• Expanded imaging modalities: The new definition broadens acceptable chest imaging beyond traditional radiography and CT, facilitating diagnosis in resource-constrained settings 1

• Alternative hypoxemia assessment: Methods for assessing hypoxia have been expanded beyond the traditional PaO₂/FiO₂ ratio to accommodate settings where arterial blood gas analysis may not be readily available 1

• Resource-adapted criteria: Additional diagnostic criteria have been incorporated specifically for resource-limited environments, enabling earlier identification and treatment interventions 1

Critical Diagnostic Pitfalls

• PEEP requirement: The PaO₂/FiO₂ ratio must be calculated while the patient receives a minimum of 5 cmH₂O PEEP; failure to do so results in inaccurate severity staging 2, 6

• Cardiogenic exclusion: Active exclusion of cardiac failure through echocardiography is mandatory when no clear ARDS risk factor is present; passive assumption leads to misclassification 2, 6

• ARDS mimics: Diffuse interstitial lung diseases, widespread pulmonary infections, and drug-induced lung injury present identically on imaging and require alternative therapeutic approaches 2, 6

• False-positive risk: The broader 2023 criteria may include patients who do not actually have ARDS, increasing the risk of false-positive diagnoses and requiring additional verification 1

Underlying Pathophysiology

ARDS is characterized by:

• Inflammatory cascade: Leukocyte infiltration, local immune activation, and injury to alveolar endothelial and epithelial cells leading to increased pulmonary vascular permeability 2, 3

• Pulmonary edema: Acute pulmonary edema with loss of aerated lung tissue and surfactant depletion creating extensive intrapulmonary shunting 2, 3

• Histologic progression: Diffuse alveolar damage evolves through exudative, fibroproliferative, and fibrotic phases with hyaline membrane formation 2

Clinical Significance and Heterogeneity

• Mortality burden: Despite refined definitions, in-hospital mortality remains approximately 30-40% across all ARDS patients 5, 2

• Multidimensional heterogeneity: ARDS encompasses wide variation across aetiological, physiological, and biological domains with no single criterion required for diagnosis 5, 2

• Therapeutic implications: This intrinsic heterogeneity has contributed to repeated failures of therapeutic trials, as interventions targeting specific pathophysiological mechanisms may only benefit selected subgroups 2, 7

• Precision medicine need: The lack of a common presentation implies that future intervention studies must be phenotype-aware and apply precision medicine approaches to identify treatable traits representing specific pathobiological mechanisms 5, 8