Causes of Acute Respiratory Distress Syndrome (ARDS)
Direct (Pulmonary) Causes
Direct lung injury occurs when the initial insult directly damages the alveolar epithelium and pulmonary structures. 1
- Pneumonia – The most common direct cause, accounting for a significant proportion of ARDS cases and associated with increased risk of right ventricular failure 1, 2
- Aspiration – Gastric contents or other materials directly injure the alveolar-capillary membrane 3, 4
- Pulmonary contusion – Blunt chest trauma causing direct parenchymal injury 5
- Inhalation injury – Toxic fumes, smoke, or chemical exposure damaging airway and alveolar structures 5
- Near-drowning – Direct alveolar flooding and surfactant washout 5
- Fat embolism – Typically following long bone fractures, causing direct microvascular obstruction 5
Indirect (Extrapulmonary) Causes
Indirect lung injury results from systemic inflammatory processes that secondarily affect the pulmonary vasculature and alveoli. 3
- Sepsis – The leading indirect cause, with 25-42% of septic patients developing ARDS, particularly those with persistent arterial hypotension 1, 2, 4
- Non-pulmonary trauma – Major trauma with shock and tissue injury triggering systemic inflammatory response 5, 4
- Pancreatitis – Severe acute pancreatitis releases inflammatory mediators systemically 5, 6
- Multiple transfusions – Transfusion-related acute lung injury (TRALI) from antibody-mediated or non-immune mechanisms 5
- Drug overdose – Certain medications and illicit drugs causing systemic toxicity 5
- Cardiopulmonary bypass – Systemic inflammatory response from extracorporeal circulation 5
- Burns – Extensive burns triggering massive systemic inflammation even without inhalation injury 5
Common Pathophysiological Pathway
Regardless of the initial trigger, all causes converge on a common mechanism: 3, 6
- Inflammatory mediator release promotes leukocyte infiltration and local immune activation 3
- Alveolar-capillary barrier damage increases pulmonary vascular permeability 3, 6
- Protein-rich pulmonary edema accumulates in interstitial and alveolar spaces 6
- Surfactant depletion and inactivation worsens lung compliance 2, 3
- Extensive intrapulmonary shunting produces profound hypoxemia 2
Critical Clinical Context
The specific etiology matters prognostically: pneumonia as the underlying cause carries higher risk of right ventricular failure (>60% when combined with other risk factors) compared to other triggers. 7, 2 This distinction should guide monitoring intensity and hemodynamic management strategies, particularly regarding ventilator settings that affect RV afterload.