What is the management approach for Acute Respiratory Distress Syndrome (ARDS) and its mimics?

ARDS Mimics: Recognition and Management

The most critical step in managing ARDS is establishing a diagnostic protocol to identify treatable diseases that mimic ARDS, as these conditions require specific therapies rather than standard ARDS management and may be inappropriately included in the syndrome diagnosis if additional diagnostic testing is not performed. 1

What Are ARDS Mimics?

ARDS mimics are conditions that present with similar clinical characteristics to ARDS—bilateral pulmonary opacities, hypoxemia, and respiratory failure—but have distinct pathophysiology requiring specific treatment. These include:

• Diffuse interstitial acute lung diseases (such as acute interstitial pneumonitis, organizing pneumonia) 1
• Diffuse pulmonary infections requiring specific antimicrobial therapy 1
• Drug/chemical-induced diffuse lung disease (including vaping-induced lung injury) 1
• Cardiogenic pulmonary edema (which requires fundamentally different fluid and hemodynamic management) 2
• Acute eosinophilic pneumonia and other immunologic lung diseases 1

Why Recognition Matters

Only a minority of patients who fulfill current ARDS criteria actually have diffuse alveolar damage on pathological evaluation, highlighting the heterogeneity within the syndrome diagnosis. 1 This matters because:

• Many ARDS mimics respond to immunosuppressants (particularly corticosteroids), antimicrobials, or withdrawal of the offending agent 1
• Standard ARDS management may be ineffective or harmful in these conditions 1
• The rapid discovery of dexamethasone for severe COVID-19 pneumonia demonstrates the importance of recognizing underlying etiology for phenotype-specific treatment 1

Diagnostic Approach

There is currently no consistent diagnostic approach that systematically accounts for the probability of ARDS mimics, representing a critical gap in clinical practice. 1 However, the following should be pursued:

Essential Diagnostic Steps

• Detailed exposure history: Recent medications, vaping, occupational exposures, travel history 1
• Infectious workup: Bronchoalveolar lavage with comprehensive cultures, viral panels, fungal studies, and consideration of endemic infections (tuberculosis, parasitic diseases in appropriate regions) 1
• Immunologic evaluation: Consider autoimmune serologies, eosinophil counts if clinical suspicion exists 1
• Cardiac assessment: Echocardiography and hemodynamic monitoring to exclude cardiogenic pulmonary edema, particularly when clinical features suggest volume overload 2
• Drug review: Systematic evaluation of all medications and supplements for potential pulmonary toxicity 1

Key Distinguishing Features

Cardiogenic pulmonary edema differs from ARDS in several critical ways:

• Responds to diuresis and afterload reduction rather than conservative fluid management 2
• Benefits from positive pressure ventilation (CPAP/BiPAP) primarily through hemodynamic effects (reducing preload/afterload) 2
• Does not require lung-protective low tidal volume ventilation strategies 2
• PEEP is titrated to optimize oxygenation without compromising cardiac output, rather than to prevent atelectrauma 2

Management Implications

When ARDS Mimic Is Identified

Specific treatment should be initiated immediately based on the underlying diagnosis:

• Drug-induced lung injury: Withdraw offending agent 1
• Infectious etiologies: Targeted antimicrobial therapy 1
• Immunologic conditions: Consider corticosteroids or other immunosuppression 1
• Cardiogenic pulmonary edema: Diuresis, vasodilators, and hemodynamic optimization rather than conservative fluid strategy 2

When True ARDS Is Confirmed

Proceed with evidence-based ARDS management:

• Lung-protective ventilation: Tidal volumes 4-8 ml/kg predicted body weight, plateau pressure ≤30 cmH₂O 1, 2
• Conservative fluid management: Minimize pulmonary edema while maintaining organ perfusion 2
• Prone positioning: >12 hours daily for severe ARDS (PaO₂/FiO₂ <100 mmHg) 1
• Higher PEEP: In moderate to severe ARDS without prolonged recruitment maneuvers 1
• Corticosteroids: Consider in selected patients, particularly with fibroproliferation 1
• VV-ECMO: For refractory severe ARDS at experienced centers 1

Critical Pitfalls to Avoid

The most dangerous error is treating ARDS mimics with standard ARDS protocols when specific therapy is needed:

• Applying conservative fluid management to cardiogenic pulmonary edema may delay appropriate diuresis 2
• Missing drug-induced lung injury allows continued exposure to the causative agent 1
• Failing to identify treatable infections results in inadequate antimicrobial coverage 1
• Including ARDS mimics in clinical trials without additional diagnostic testing contaminates study populations and may obscure treatment effects 1

Iatrogenic "Second Hits"

Even in true ARDS, pulmonary edema can be caused or aggravated by iatrogenic factors that should be considered additional insults:

• Excessive fluid administration 1
• Blood product transfusions 1
• Injurious mechanical ventilation 1

These second hits add complexity to the syndrome and should be meticulously avoided through lung-protective ventilation, conservative fluid strategies, and judicious transfusion practices. 1

Research Priorities

Future clinical trials must take particular care to identify and potentially exclude patients with ARDS-mimic diagnoses, depending on the intervention being studied. 1 Establishing standardized diagnostic protocols to distinguish ARDS from its mimics is essential for both clinical care and research integrity. 1