Acute Respiratory Distress Syndrome (ARDS) is a severe, life-threatening inflammatory lung injury characterized by rapid onset of widespread inflammation in the lungs, leading to increased pulmonary vascular permeability, lung edema, loss of aerated lung tissue, and severe hypoxemia refractory to oxygen therapy. It is not primarily due to cardiac failure or fluid overload and typically develops as a complication of an underlying critical illness or injury.

ARDS is triggered by various direct and indirect insults to the lungs.

• Direct Lung Injury: Pneumonia (bacterial, viral, fungal, parasitic), aspiration of gastric contents, severe trauma (e.g., lung contusion), near-drowning, inhalation injury, re-expansion pulmonary edema, pulmonary vasculitis.


• Indirect Lung Injury: Sepsis (most common cause), severe non-thoracic trauma with shock and multiple transfusions, acute pancreatitis, severe burns, drug overdose, massive blood transfusion (TRALI), systemic inflammatory response syndrome (SIRS).


• Genetic Factors: While not a primary cause, genetic predispositions related to inflammatory responses (e.g., specific HLA alleles, cytokine polymorphisms) may influence susceptibility and severity.

ARDS begins with an acute injury to the alveolar-capillary membrane, leading to its increased permeability.

1. Exudative Phase (0-7 days): Endothelial and epithelial cell damage results in protein-rich fluid, inflammatory cells (neutrophils), and cytokines (IL-1, IL-6, TNF-α) leaking into the alveolar space and lung interstitium. This causes non-cardiogenic pulmonary edema. Surfactant production is impaired or inactivated, leading to alveolar collapse (atelectasis) and reduced lung compliance. Hyaline membranes, composed of necrotic epithelial cells and plasma proteins, form on alveolar walls. Gas exchange is severely impaired, causing shunt and severe hypoxemia.


2. Proliferative Phase (7-21 days): If the patient survives, there is an attempt at repair. Type II pneumocytes proliferate to replace damaged Type I cells. Fibroblasts also proliferate, leading to collagen deposition and early fibrosis.


3. Fibrotic Phase (after 3 weeks): In some patients, uncontrolled fibrotic activity results in extensive collagen deposition, leading to lung remodeling, honeycomb changes, and long-term pulmonary dysfunction.

The incidence of ARDS varies significantly but is estimated to be between 10 to 80 cases per 100,000 person-years in developed countries. It can affect individuals of all ages, from neonates to the elderly, with a higher incidence in older adults due to increased comorbidities. There is generally no significant gender predominance, though some studies suggest a slight male predominance in certain cohorts.

• Sepsis (most common)
• Pneumonia (bacterial, viral, fungal, COVID-19)
• Aspiration of gastric contents
• Severe trauma (especially with multiple transfusions)
• Acute pancreatitis
• Drug overdose
• Massive blood transfusion (Transfusion-Related Acute Lung Injury - TRALI)
• Near-drowning
• Inhalation injury
• Burns
• Immunosuppression
• Chronic alcohol abuse

A. Early Symptoms

• Dyspnea (shortness of breath)


• Tachypnea (rapid breathing)


• Cough


• Restlessness and anxiety


• Mild hypoxemia B. Common Symptoms


• Profound dyspnea at rest


• Severe hypoxemia refractory to high-flow oxygen


• Use of accessory muscles for breathing


• Tachycardia


• Diffuse bilateral crackles (rales) on lung auscultation


• Cyanosis (bluish discoloration of skin/mucosa) C. Advanced Symptoms


• Multi-organ dysfunction (e.g., acute kidney injury, liver dysfunction)


• Hypotension (if associated with sepsis or shock)


• Altered mental status (confusion, somnolence)


• Arrhythmias D. Emergency Symptoms


• Acute, severe respiratory distress


• Severe cyanosis


• Significantly altered level of consciousness


• Signs of cardiogenic shock (e.g., very low blood pressure, clammy skin)


• Cardiac arrest

• Vital Signs: Tachypnea, tachycardia, hypoxemia (low SpO2), possibly hypotension (if associated with shock or sepsis). Fever may be present.
• Inspection: Increased work of breathing, use of accessory respiratory muscles, nasal flaring, suprasternal/intercostal retractions, cyanosis.
• Palpation: Normal vocal fremitus or decreased in areas of consolidation/effusion.
• Auscultation: Diffuse bilateral fine to coarse crackles (rales), often late finding. Breath sounds may be diminished. Wheezing is uncommon.

Diagnosis of ARDS is based on clinical criteria (Berlin Definition).
A. Clinical Assessment
History of an underlying risk factor for ARDS. Evaluation of symptoms (dyspnea, hypoxemia).
B. Laboratory Testing
Includes arterial blood gas analysis, complete blood count, inflammatory markers, cardiac biomarkers, and cultures to identify underlying cause.
C. Imaging Studies
Chest X-ray and Computed Tomography (CT) of the chest are crucial.
D. Functional Tests
Pulmonary function tests are not used for acute diagnosis but lung compliance measurements on mechanical ventilation indicate severity.
E. Biopsy Findings
Lung biopsy is rarely performed for diagnosis of ARDS but would show diffuse alveolar damage (DAD) in the exudative phase.
F. Genetic Testing
Not routinely used for diagnosis.
G. Differential Diagnosis
Distinguishing ARDS from cardiogenic pulmonary edema is critical.

Arterial Blood Gas (ABG)
Type: Blood Test
Purpose: Assess oxygenation, ventilation, and acid-base status. Essential for diagnostic criteria (PaO2/FiO2 ratio).
Expected Findings: Severe hypoxemia (low PaO2), often initially with respiratory alkalosis (compensatory tachypnea), progressing to metabolic acidosis.
Interpretation: PaO2/FiO2 ratio: Mild ARDS (201-300 mmHg), Moderate ARDS (101-200 mmHg), Severe ARDS (≤100 mmHg). Complete Blood Count (CBC)
Type: Blood Test
Purpose: Evaluate for infection, inflammation, or anemia.
Expected Findings: Leukocytosis (elevated white blood cell count) often indicates infection/inflammation; potentially anemia from critical illness.
Interpretation: Elevated WBC, especially with a left shift, supports an inflammatory or infectious etiology. Inflammatory Markers (C-reactive protein, Procalcitonin)
Type: Blood Test
Purpose: Assess systemic inflammation and guide antibiotic therapy (procalcitonin).
Expected Findings: Markedly elevated CRP; elevated procalcitonin suggestive of bacterial infection/sepsis.
Interpretation: High levels indicate significant inflammation, and procalcitonin can help differentiate bacterial from non-bacterial causes. Brain Natriuretic Peptide (BNP) or N-terminal pro-BNP (NT-proBNP)
Type: Blood Test
Purpose: Differentiate ARDS from cardiogenic pulmonary edema.
Expected Findings: Typically normal or mildly elevated in ARDS, significantly elevated in cardiogenic pulmonary edema.
Interpretation: Low levels help rule out cardiac failure as the primary cause of pulmonary edema.