- Clinical science
Acute respiratory distress syndrome (ARDS) is a severe inflammatory reaction of the lungs to pulmonary damage. While sepsis is the most common cause, a variety of systemic and pulmonary factors (e.g., pneumonia, aspiration) can lead to ARDS. Affected individuals initially present with acute-onset cyanosis, dyspnea, and tachypnea. The chief finding in ARDS is hypoxemic respiratory failure with decreased arterial oxygen pressure, which can progress to hypercapnic respiratory failure. Chest x-ray typically shows diffuse bilateral infiltrates. A defining laboratory feature of ARDS is a PaO2/FiO2 ratio ≤ 300 mm Hg. Management of ARDS is focused on maintaining adequate oxygenation, which often requires intubation and lung-protective mechanical ventilation. Moreover, any treatable causes of ARDS should be addressed. Even if adequate treatment is initiated, ARDS remains an acutely life-threatening disease with a high mortality rate. Most patients improve significantly in the weeks following the initial presentation, but some cases progress to pulmonary fibrosis, which prolongs hospital stays and delays the resolution of symptoms.
(most common cause)
- E.g., secondary to trauma, infection or peritonitis
- Massive TRALI” for details) (See “
- Hematopoietic stem cell transplantation
- Medication (e.g., salicylic acid, tricyclic antidepressants, bleomycin)
- Recreational drug overdose (e.g., cocaine)
Primary damage to the lungs
- Inhaled toxins
- Pulmonary contusion
- Inhalation injury (e.g., inhalation of hyperbaric oxygen)
- Near drowning
- Fat embolism (e.g., through blunt trauma)
- Amniotic fluid embolism (e.g., during labor)
- Lung transplantation
Sepsis is the most common cause of ARDS!
Tissue damage (pulmonary or extrapulmonary) → release of inflammatory mediators (e.g., interleukin-1) → inflammatory reaction → migration of neutrophils into alveoli → excessive release of neutrophilic mediators (e.g., cytokines, proteases, reactive oxygen species) → injury to alveolar capillaries and endothelial cells (diffuse alveolar damage, DAD) leading to:
- Exudative phase: excess fluid in interstitium and on alveolar surface → pulmonary edema with normal pulmonary capillary wedge pressure (noncardiogenic pulmonary edema) → decreased lung compliance and respiratory distress
Hyaline membrane formation: exudation of neutrophils and protein-rich fluid into the alveolar space → formation of alveolar hyaline membranes → impaired gas exchange → hypoxemia
- Hypoxemia → compensation through hyperventilation → respiratory alkalosis
- Hypoxemia → chronic hypoxic pulmonary vasoconstriction → pulmonary hypertension and right-to-left pulmonary shunt (increased shunt fraction)
- Damage to type I and type II pneumocytes → decrease in surfactant → alveolar collapse → intrapulmonary shunting →
- Organizing phase (late stage): proliferation of type II pneumocytes and infiltration of fibroblasts → progressive interstitial fibrosis
ARDS is a diagnosis of exclusion (see the Berlin criteria for ARDS). Consider ARDS in patients with rapid-onset respiratory failure and a potential trigger.
- Order chest x-ray to evaluate for characteristic findings (bilateral infiltrates).
- Perform an ABG and calculate the P/F ratio.
- Consider additional testing in order to:
- Identify triggers
- Rule out differential diagnoses
- Assess potential complications
The Berlin criteria are the criteria most commonly used to define ARDS. All four of the following conditions must be met: 
- Acute onset: respiratory failure within one week of a known predisposing factor (e.g., sepsis, pneumonia) or worsening respiratory symptoms
- Bilateral opacities (on chest x-ray or CT)
- Hypoxemia: PaO2/FiO2 ≤ 300 mm Hg (measured with a minimum of 5 cm H2O PEEP) 
- Respiratory failure cannot be fully accounted for by heart failure or fluid overload.
ARDS diagnostic criteria include: Abnormal x-ray, Respiratory failure < 1 week after a known or suspected trigger, Decreased PaO2/FiO2, Should exclude CHF or fluid overload as a potential cause of respiratory distress.
Chest x-ray is usually sufficient for diagnosis. However, distinguishing between ARDS and CHF can be challenging. In these cases, correlation with other tests (e.g., CT chest, lung ultrasound, echocardiogram) may be useful.
Chest x-ray 
- Indications: all patients suspected of having ARDS
- Acute findings (1–7 days)
Intermediate (8–14 days) to late (> 15 days) findings
- Typical course: Acute features remain stable, then resolve.
- Fibrotic course: Reticular opacities begin to appear and may become permanent.
- Findings supportive of ARDS rather than CHF
CT chest without contrast 
- Indications: may be used if chest x-ray findings are insufficient or to further investigate for underlying causes or complications
Acute findings (1–7 days)
- Symmetrical ground-glass opacities are the most important finding.
- Gravity-dependent density gradient
- The lungs may appear normal in nondependent regions.
- Dense consolidation in dependent regions
- Bronchial dilatation may be visible.
- Additional findings may include small pleural effusions, air bronchograms (see “Chest x-ray” above).
Intermediate (8–14 days) to late (> 15 days) findings: a phase of stability is followed either by resolution or progressive development of fibrosis
- Mixed findings may be seen.
- Potential long-term persistence of ground-glass opacities
- Cysts and bullae may develop.
Lung ultrasound 
- Indications: may be helpful in differentiating between cardiogenic pulmonary edema and ARDS
- Bilateral B pattern
- C pattern (consolidation)
- Abnormal pleural line (thickening, irregular pattern, and/or alterations in lung sliding)
Laboratory studies 
- Arterial blood gas
Additional laboratory studies to consider
- Underlying causes/triggers
- Differential diagnoses
- Complications: See diagnostics in acute kidney injury, sepsis, and DIC.
Additional diagnostic studies 
- ECG: Signs of STEMI, LVH, or cardiac arrhythmias may indicate CHF.
- Echocardiography: to exclude or assess the degree of heart failure 
- Bronchoscopy with bronchoalveolar lavage (BAL) 
- Right heart catheterization
- Lung biopsy: consider in rare cases 
- Address hypoxemia (see oxygen therapy, airway management).
- Apply lung-protective ventilation strategies.
- Augment therapy as needed based on severity (see the Berlin criteria for ARDS).
- Identify and treat the underlying cause (e.g., pneumonia, pancreatitis, sepsis).
All patients with ARDS 
The foundation of management in all patients with ARDS consists of treating hypoxemia, lung-protective ventilation (to minimize further lung damage), treatment of the underlying cause, and supportive care.
Oxygenation: Hypoxemia is a hallmark feature of ARDS and should be addressed immediately.
- Noninvasive methods: See oxygen therapy
- Invasive methods
Lung-protective ventilation: All patients with ARDS should be treated with lung-protective ventilation to decrease the risk of VILI. 
- General initial settings include:
- Allow for permissive hypercapnia
- PEEP and FiO2 can be adjusted to recruit collapsed alveoli and improve oxygenation.
- See lung-protective ventilation strategy for more information and specific parameter settings.
- Supportive care
- Identify and treat the underlying cause: See “Etiology”.
- Additional considerations: Early ICU consultation is advised.
Moderate to severe ARDS 
Prone positioning 
- P/F ratio < 150 mm Hg
- Pulmonary edema
- Relative contraindications include: 
- Duration: typically done for at least 12–16 hours/day
- Complications include:
Lung recruitment maneuvers 
- Definition: a series of treatment measures that increase the surface area of lung available for gas exchange
|ARDSnet protocol for FiO2/PEEP titration |
|Low PEEP/high FiO2 strategy|
|FiO2 (%)||PEEP (cm H2O)|
|High PEEP/Low FiO2 strategy|
- Neuromuscular blockade 
- Corticosteroids: Consider in early ARDS. 
Severe ARDS with persistent hypoxemia (rescue therapy) 
The following interventions should only be considered with expert consultation and when guideline-recommended treatments have failed.
- Consider alternative ventilator settings (e.g., mode, parameters, or overall strategy): See mechanical ventilation.
- Consider experimental therapies (e.g., inhaled vasodilators such as nitric oxide or prostacyclin). 
ECMO: method of supporting the O2/CO2 exchange through the use of artificial lung membranes 
- Consider ECMO in the following patients: 
- The Murray score for ARDS can also be used to identify patients who may benefit from ECMO. 
|Murray score for ARDS |
|Clinical parameter||Findings||Points assigned|
|Alveolar consolidation on x-ray||None||0|
|1 quadrant involved||1|
|2 quadrants involved||2|
|3 quadrants involved||3|
|4 quadrants involved||4|
|P/F ratio in mm Hg||> 300||0|
|PEEP in cm H2O||≤ 5||0|
|Respiratory compliance in mL/cm H2O||> 80||0|
Interpretation: Add up the total points and divide the total by the number of parameters present.
All patients with ARDS 
- Perform ABCDE survey.
- Call for help early: Consult ICU and/or rapid response team.
- Optimize oxygenation.
- Quantify hypoxemia: Use the P/F ratio to evaluate ARDS severity. 
- If there are signs of airway compromise: See
- Start lung-protective ventilation strategy. 
- Ensure euvolemia.
- Hemodynamic monitoring
- Monitor mechanical ventilation: capnography, pressure monitoring, and ABG checks.
- Reassess ventilation settings and strategy as needed. 
- Supportive care: See adjunctive care of ventilated patients for pain management and sedation.
- Identify and treat the underlying cause.
- ICU admission
Moderate or severe ARDS
- Consider prone positioning for > 12–16 hours/day. 
- Use incremental FiO2-PEEP combinations based on ARDSnet protocol.
- Consider lung recruitment maneuvers.
- Consider neuromuscular blockade: Start in the first 48 hours. 
Severe ARDS with persistent hypoxemia
- Disease course
- In patients with simultaneous multiorgan failure, the mortality rate is 30–50%. 
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