What is Acute Respiratory Distress Syndrome (ARDS)?
ARDS is an acute inflammatory syndrome characterized by increased pulmonary capillary leakage leading to non-cardiogenic interstitial and alveolar pulmonary edema, manifesting as rapidly progressive dyspnea, tachypnea, and profound hypoxemia that cannot be explained by cardiac failure or fluid overload. 1, 2
Diagnostic Criteria
The Berlin Definition establishes four required elements for ARDS diagnosis: 1, 3
- Timing: Acute onset within one week of a known clinical insult or new/worsening respiratory symptoms 1, 2
- Imaging: Bilateral pulmonary opacities on chest radiography that cannot be fully explained by effusions, lobar/lung collapse, or nodules 1, 4
- Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload (must rule out cardiogenic causes) 1, 3
- Oxygenation defect: Profound hypoxemia measured by PaO₂/FiO₂ ratio with minimum PEEP of 5 cmH₂O 1, 3
Severity Classification
ARDS is stratified into three categories based on the degree of hypoxemia (all measured with PEEP ≥5 cmH₂O): 1, 3, 4
- Mild ARDS: PaO₂/FiO₂ ratio 200-300 mmHg 1, 3
- Moderate ARDS: PaO₂/FiO₂ ratio 100-200 mmHg 1, 3
- Severe ARDS: PaO₂/FiO₂ ratio ≤100 mmHg 1, 3
Pathophysiology
The underlying mechanisms involve a cascade of inflammatory damage: 1, 5, 6
- Inflammatory mediator release from pulmonary or extrapulmonary insults triggers neutrophil and cytokine accumulation in alveoli and lung microcirculation 2, 5
- Alveolar epithelial inflammation with airspace flooding by plasma proteins and cellular debris 1
- Vascular endothelial and alveolar epithelial damage leading to increased capillary permeability 2, 5
- Surfactant depletion and inactivation with hyaline membrane formation 1, 2
- Loss of normal endothelial reactivity and extensive right-to-left intrapulmonary shunting causing refractory hypoxemia 1, 5
Common Etiologies
Most cases are associated with: 2, 6
- Pneumonia (most common direct pulmonary cause) 2
- Sepsis (most common extrapulmonary cause) 2, 6
- Aspiration 6
- Trauma 6
- Blood transfusion (transfusion-related acute lung injury) 7, 6
- Severe acute pancreatitis 6
Epidemiology and Outcomes
ARDS represents a significant critical care burden: 2, 4
- Affects approximately 200,000 patients annually in the United States with nearly 75,000 deaths per year 4
- Accounts for 10% of ICU admissions globally (>3 million patients annually) 4
- Responsible for one in four mechanical ventilations 2
- In-hospital mortality ranges from 34.8% (28-day) to 46-60% for severe ARDS, though this has improved from historical rates of 60-70% 8, 2, 6
- Development occurs in 25-42% of sepsis patients, with increased risk in those with persistent arterial hypotension 1
Clinical Course and Natural History
The syndrome's progression is typically dominated by the inciting event rather than lung injury itself: 8
- Death from refractory respiratory failure is unusual; multiple organ failure or recurrent sepsis are the most common causes of death 8
- Patients resolving ARDS rapidly (10-14 days) show parallel decreases in minute ventilation and dead-space ventilation with oxygenation improvements 8
- Patients with severe ARDS developing significant fibrosis maintain high minute ventilatory requirements even as oxygenation improves, due to progressive vascular bed obliteration 8
Critical Diagnostic Pitfalls
Avoid these common errors in ARDS recognition: 1, 3
- Misattribution of pulmonary edema to cardiogenic causes can lead to misclassification; actively rule out cardiac failure and fluid overload 1, 3
- Failure to calculate PaO₂/FiO₂ ratio with patients on at least 5 cmH₂O PEEP invalidates severity classification 3
- Clinician interpretation of chest radiograph criteria and origin of edema may be unreliable, contributing to underrecognition of ARDS 4
- Only a minority of patients meeting clinical criteria demonstrate diffuse alveolar damage on pathological evaluation, revealing disconnect between clinical diagnosis and underlying pathology 7