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

Definition of Acute Respiratory Distress Syndrome (ARDS)

ARDS is defined as acute hypoxemic respiratory failure characterized by bilateral pulmonary opacities on chest imaging developing within 1 week of a known clinical insult, with impaired oxygenation (PaO₂/FiO₂ ratio measured at minimum 5 cmH₂O PEEP), where cardiac failure does not fully explain the clinical presentation. 1

Core Diagnostic Criteria

The diagnosis requires all four of the following elements:

• Timing: Acute onset within 1 week of a known clinical insult or new/worsening respiratory symptoms 1, 2
• Imaging: Bilateral pulmonary opacities on chest radiograph or CT that cannot be fully explained by pleural effusions, lobar collapse, or nodules 1, 3
• Oxygenation impairment: PaO₂/FiO₂ ratio must be calculated while receiving at least 5 cmH₂O of positive end-expiratory pressure (PEEP) 3, 1
• Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload; when no clear ARDS risk factor exists, objective cardiac assessment (echocardiography) must exclude hydrostatic pulmonary edema 1, 2

Severity Classification

ARDS severity is stratified based on the degree of hypoxemia while on minimum 5 cmH₂O PEEP:

• Mild ARDS: PaO₂/FiO₂ ratio 200-300 mmHg 4
• Moderate ARDS: PaO₂/FiO₂ ratio 100-200 mmHg 4
• Severe ARDS: PaO₂/FiO₂ ratio ≤100 mmHg 4

Pathophysiological Characteristics

ARDS represents a devastating critical illness with distinct pathophysiologic features:

• Inflammatory injury: Leukocyte infiltration and local immune activation with injury to alveolar endothelial and epithelial cells 3, 1
• Increased vascular permeability: Damage to the alveolar-capillary barrier leads to increased pulmonary vascular permeability 3, 1
• Pulmonary edema: Acute pulmonary edema with protein-rich fluid extravasation into the airspace and loss of aerated lung tissue 3, 5
• Surfactant dysfunction: Surfactant depletion and inactivation contribute to alveolar collapse 1
• Gas exchange impairment: Profound hypoxemia results from intrapulmonary shunting and ventilation-perfusion mismatch 1

Critical Diagnostic Pitfalls

PEEP requirement: The PaO₂/FiO₂ ratio must be measured at a minimum of 5 cmH₂O PEEP; failure to do so results in inaccurate severity staging and potential misclassification 1

Cardiac exclusion failure: Clinicians must actively rule out cardiogenic pulmonary edema via echocardiography when the diagnosis is uncertain, as misclassification leads to inappropriate management 1

Radiographic interpretation: Standard chest radiographs show poor correlation with oxygenation severity and clinical outcomes; infiltrates may be asymmetric or patchy rather than diffuse, potentially causing diagnostic confusion 3

ARDS mimics: Diffuse interstitial lung diseases, widespread pulmonary infections, and drug-induced lung injury can present identically to ARDS on imaging and require alternative therapeutic approaches 1

Inherent Heterogeneity

No specific etiological, physiological, or biological criteria are required for ARDS diagnosis, creating profound heterogeneity across all three domains. 3 This heterogeneity has three critical implications:

• Aetiological variation: ARDS can be triggered by direct pulmonary insults (pneumonia, aspiration) or indirect extrapulmonary insults (sepsis, pancreatitis), with no requirement to specify the cause for diagnosis 3
• Physiological variation: Patients demonstrate wide variation in respiratory mechanics, dead space ventilation, and ventilatory requirements despite meeting identical diagnostic criteria 3
• Biological variation: Only a minority of patients meeting clinical ARDS criteria demonstrate diffuse alveolar damage on pathological examination, revealing fundamental disconnect between clinical diagnosis and underlying pathology 6

This multidimensional heterogeneity has contributed to decades of failed therapeutic trials, as interventions targeting specific pathophysiological mechanisms benefit only selected subgroups while exposing others to potential harm without benefit 3, 6

Clinical Outcomes

In-hospital mortality for ARDS remains approximately 30-40% despite advances in supportive care. 3, 1 Death results primarily from multiorgan failure and unresolved sepsis rather than isolated respiratory failure 3, 7