What is the most likely cause of hypoxemia in a patient with a history of respiratory infection, presenting with shortness of breath (SOB), normal blood pressure (BP), tachypnea (respiratory rate of 22), severe hypoxemia (oxygen saturation of 78%) and low partial pressure of oxygen (Po2 of 5 kPa)?

Most Likely Diagnosis: Pulmonary Edema (ARDS)

The most likely cause is pulmonary edema, specifically acute respiratory distress syndrome (ARDS) developing as a complication of the recent respiratory infection. This patient presents with the classic triad of post-infectious ARDS: progressive dyspnea following respiratory infection, severe hypoxemia (PO2 5 kPa/38 mmHg, SpO2 78%) with preserved ventilation (normal pH, PCO2, HCO3), and tachypnea—all hallmarks of Type 1 respiratory failure from ventilation-perfusion mismatch and intrapulmonary shunting 1.

Clinical Reasoning Algorithm

Why ARDS/Pulmonary Edema (Answer D):

• Timeline matches perfectly: ARDS typically develops 1-5 days after the initial insult, and this patient is presenting on day 5 post-respiratory infection 1
• Severe hypoxemia with normal ventilation: PO2 of 5 kPa (38 mmHg) with normal PCO2 indicates Type 1 respiratory failure, the defining feature of ARDS 1, 2
• Progressive dyspnea: The 5-day progression of increasing shortness of breath reflects the evolving phases of ARDS—from initial interstitial edema to alveolar flooding with proteinaceous material and hyaline membrane formation 1
• Tachypnea without hypercapnia: Respiratory rate of 22 represents compensatory hyperventilation attempting to correct hypoxemia, resulting in normal or low PCO2 2
• Post-infectious context: Between 28-33% of patients with sepsis/respiratory infections develop ARDS, making this the most common post-infectious pulmonary complication 1

Why NOT the Other Options:

COPD (Answer A) is excluded because:

• COPD patients typically present with Type 2 respiratory failure (elevated PCO2, respiratory acidosis), not isolated hypoxemia with normal PCO2 1, 2
• The acute 5-day progression is inconsistent with COPD exacerbation patterns
• No mention of chronic smoking history or baseline lung disease 1

Drug overdose (Answer B) is excluded because:

• Opioid or sedative overdose causes hypoventilation with elevated PCO2 and respiratory acidosis, not isolated hypoxemia 2
• The ABG would show elevated PCO2 and low pH, which this patient does not have
• The 5-day progressive course doesn't fit acute intoxication 2

Myasthenia gravis (Answer C) is excluded because:

• Myasthenic crisis causes neuromuscular respiratory failure with hypercapnia (Type 2 failure), not isolated hypoxemia 2
• Would expect elevated PCO2 from inadequate ventilation due to respiratory muscle weakness
• No mention of characteristic features like diplopia, ptosis, or fluctuating weakness
• The post-infectious timeline points away from primary neuromuscular disease 2

Pathophysiological Mechanism

The severe hypoxemia (PO2 5 kPa) despite normal ventilation occurs through two primary mechanisms in ARDS 1, 3:

1. Ventilation-perfusion (V/Q) mismatch: Alveolar flooding with proteinaceous edema creates areas of perfused but non-ventilated lung 1, 3, 4
2. Intrapulmonary shunting: Blood flows through completely collapsed or fluid-filled alveoli without gas exchange, creating a physiological right-to-left shunt 1, 3, 5

The normal PCO2 despite severe hypoxemia occurs because CO2 is 20 times more diffusible than oxygen—even diseased alveoli can eliminate CO2 effectively while failing to oxygenate blood 2, 3.

Critical Management Priorities

Immediate oxygen therapy is life-saving and must not be delayed 6, 7:

• Start with reservoir mask at 15 L/min immediately for SpO2 <85% 6, 7
• Target SpO2 94-98% (this patient has no COPD risk factors for hypercapnia) 6, 7
• Obtain arterial blood gas to confirm diagnosis and guide ventilatory support 6, 2
• Prepare for possible mechanical ventilation if oxygen therapy fails—PO2 of 5 kPa represents life-threatening hypoxemia 1, 6

Common Pitfalls to Avoid

• Do not withhold oxygen due to concerns about CO2 retention when PO2 is critically low (5 kPa)—the immediate risk of hypoxic brain injury outweighs theoretical hypercapnia concerns 6, 7
• Do not assume "normal examination findings" excludes serious pathology—early ARDS may have minimal auscultatory findings despite severe gas exchange abnormalities 1
• Do not delay treatment while obtaining chest X-ray—radiographic changes in ARDS often lag behind physiological derangements by hours to days 1
• The absence of fever does not exclude ARDS, as the patient is 5 days post-infection and may be in the fibroproliferative phase 1

This clinical presentation of progressive post-infectious hypoxemia with preserved ventilation is pathognomonic for ARDS developing as a complication of respiratory infection 1, 2.