What is the most likely cause of increasing shortness of breath (SOB) and hypoxemia in a 38-year-old male with a history of respiratory infection 5 days ago, presenting with tachypnea (respiratory rate 22), severe hypoxemia (oxygen saturation 78%), and low partial pressure of oxygen (PO2 5 kPa) on arterial blood gas (ABG) analysis?

Acute Respiratory Distress Syndrome (ARDS) Following Respiratory Infection

The most likely diagnosis is D. Pulmonary edema (specifically ARDS, which is a form of non-cardiogenic pulmonary edema), as this 38-year-old male presents with the classic triad of Type 1 respiratory failure: severe hypoxemia (PO2 5 kPa, SpO2 78%), preserved ventilation (normal pH, PCO2, HCO3), and progressive dyspnea developing 5 days after a respiratory infection. 1, 2

Why ARDS is the Correct Answer

The clinical presentation is pathognomonic for ARDS:

• The American Thoracic Society confirms that ARDS presents with severe hypoxemia (PO2 5 kPa/38 mmHg, SpO2 78%) with preserved ventilation (normal pH, PCO2, HCO3), which are hallmarks of Type 1 respiratory failure from ventilation-perfusion mismatch and intrapulmonary shunting 1

• The 5-day timeline from respiratory infection to presentation fits the Berlin definition for ARDS, which requires "respiratory symptoms developed/aggravated within 1 week after clinically known damage" 2, 3

• The pathophysiology explains the severe hypoxemia: inflammatory exudate fills alveoli, creating non-ventilated but perfused lung units (intrapulmonary shunting), while CO2 remains normal because it is 20 times more diffusible than oxygen, allowing even diseased alveoli to eliminate CO2 effectively 1, 2

Why the Other Options Are Incorrect

A. COPD is definitively excluded:

• COPD causes Type 2 respiratory failure with elevated PCO2 (>6.0 kPa or 45 mmHg), not isolated hypoxemia with normal PCO2 1, 2
• The European Respiratory Society states that significant hypoxemia with normal PCO2 is rare in COPD unless FEV1 >1.0 L, and daytime hypercapnia is unlikely unless respiratory muscle strength is reduced to 40% of predicted 4, 1
• This patient's normal PCO2 despite severe hypoxemia rules out COPD 1

B. Drug overdose is excluded:

• Opioid or sedative overdoses cause hypoventilation with elevated PCO2 and respiratory acidosis, which is absent in this patient 1, 2
• The normal pH and PCO2 definitively rule out respiratory depressant drug overdose 1

C. Myasthenia gravis is excluded:

• Neuromuscular disorders cause Type 2 respiratory failure with hypercapnia due to ventilatory pump failure when severe enough to cause hypoxemia 1, 2
• The American Academy of Neurology confirms that myasthenia gravis would present with elevated PCO2, not normal PCO2 2

Critical Clinical Pitfall to Avoid

Do not be falsely reassured by "no examination findings":

• The Society of Critical Care Medicine warns that early ARDS may have minimal auscultatory findings despite severe gas exchange abnormalities 2
• Clinical examination alone is unreliable for diagnosing severe hypoxemia; arterial blood gas analysis (which was obtained) is essential 1

Immediate Management Required

Oxygen therapy must be initiated immediately:

• Start with high-flow nasal oxygen (HFNO) or reservoir mask at 15 L/min, targeting SpO2 >94%, as this may reduce intubation rates in Type 1 respiratory failure with large mortality reduction (ARD -15.8%) 1, 5, 2

• The American Thoracic Society emphasizes that when PO2 is critically low (5 kPa), the immediate risk of hypoxic brain injury outweighs any theoretical concerns about CO2 retention 1

Prepare for mechanical ventilation:

• If HFNO fails, intubate and use lung-protective ventilation strategies (tidal volume 6 mL/kg, plateau pressure <30 cmH2O) 2
• Obtain chest imaging urgently to confirm bilateral infiltrates consistent with ARDS 2, 3

Monitor continuously:

• Implement continuous pulse oximetry and repeat arterial blood gas analysis to assess response to therapy 5
• In-hospital mortality for severe ARDS ranges from 46% to 60%, making aggressive early intervention critical 3