Respiratory Distress Syndrome, Acute (ARDS)



  • Acute respiratory distress syndrome (ARDS) is defined as the onset of acute hypoxemia within 7 days of a known clinical insult, or new or worsening respiratory symptoms with bilateral opacities (patchy, diffuse, or homogenous) consistent with pulmonary edema on imaging. It is a diagnosis of exclusion.
  • Severity of ARDS is defined by the severity of hypoxia present, measured with a ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) at a positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) of at least 5 cm H2O.
    • Mild—200 mm Hg < PaO2/FiO2 ≤300 mm Hg
    • Moderate—100 mm Hg < PaO2/FiO2 ≤200 mm Hg
    • Severe—PaO2/FiO2 ≤100 mm Hg
  • Synonym(s): acute lung injury; increased-permeability pulmonary edema; noncardiac pulmonary edema
  • Systems affected: pulmonary, cardiovascular



  • The incidence of ARDS in the United States is estimated to range from 64.2 to 78.9 cases/100,000 person-years.
  • An estimated 10–15% of all ICU patients and approximately 23% of ventilator dependent patients meet the criteria for the diagnosis of ARDS.
  • 25% of ARDS cases are classified as mild at the time of diagnosis, whereas 75% are classified as moderate to severe. Females sex is a risk factor for ARDS.

Etiology and Pathophysiology

  • ARDS is a response to direct or indirect alveolar injury leading to diffuse alveolar damage.
    • Direct
      • Pneumonia (bacterial, viral, fungal, or opportunistic)
      • Aspiration of gastric contents
      • Near drowning
      • Pulmonary contusion
      • Inhalation injury
    • Indirect
      • Sepsis (nonpulmonary)
      • Shock
      • Transfusion of blood products
      • Major burn injury
      • Nonthoracic trauma
      • Drug overdose
      • Cardiopulmonary bypass
      • Reperfusion edema after lung transplant or embolectomy
  • Progression of the diffuse alveolar damage in ARDS is divided into three phases.
    • Exudative phase—The initial highly inflammatory phase when alveolar macrophages are activated due to lung injury, leading to complement activation, release of proinflammatory mediators, and activation of neutrophils. This causes epithelial–endothelial barrier disruption, leading to intra-alveolar and extra-alveolar flooding with fluid. This is followed by hyaline membrane formation leading to alveolar collapse.
    • Proliferative phase—The second phase characterized by fibroblasts, myofibroblasts, and alveolar epithelial cell (ACE) II mediated repair. Formation of new matrix, differentiation into ACE I, and formation of cellular junctions begins which leads to expression of aquaporin and ion channels, aiding in the reabsorption of fluid.
    • Fibrotic phase—The final phase, not experience by every patient, is characterized by prolonged mechanical ventilation and associated with increased mortality.

No single gene has been identified for clinical use.

Risk Factors

  • Patients who are at low risk may be identified by a lung injury prevention score; however, this score is less accurate in high-risk patients.
  • There are several risk factors that predispose patients to developing ARDS. These include advanced age, female sex, smoking, alcohol use, aortic or cardiovascular surgeries, and traumatic brain injury.
  • Increased levels of markers of systemic inflammation have been associated with adverse outcomes.

General Prevention

To date, there has been no effective strategy proven to prevent developing ARDS; however, measures can be taken to mitigate risk factors. Early lung protective ventilation and sepsis management have both been shown to improve clinical outcomes in ARDS.

Commonly Associated Conditions

  • Pneumonia, sepsis, and aspiration of gastric contents cause 85% of ARDS cases.
  • Other causes can include:
    • Trauma
    • Burns
    • Cardiothoracic surgery
    • Pancreatitis
    • Inhalational injuries and near drownings
    • Transfusion-related acute lung injury (TRALI)
    • Shock
    • Medication toxicity

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