What is the cause of fever in patients with pulmonary embolism (PE)?

Mechanisms of Fever in Pulmonary Embolism

Fever in pulmonary embolism is primarily caused by an inflammatory response triggered by thromboemboli, with approximately 14-25% of patients experiencing fever that can range from low-grade to high-grade (>39°C), even without pulmonary infarction or hemorrhage. 1, 2

Pathophysiological Mechanisms of Fever in PE

• Inflammatory response is triggered by the presence of thromboemboli in the pulmonary vasculature, with massive infiltrates of inflammatory cells found in the right ventricular myocardium of patients who died within 48 hours of acute PE 3

• PE-induced "myocarditis" may result from high levels of epinephrine released as part of the neurohumoral activation in response to right ventricular wall tension and circulatory shock 3

• The inflammatory response can explain secondary hemodynamic destabilization that sometimes occurs 24-48 hours after acute PE 3

• Fever can occur without evidence of pulmonary hemorrhage or infarction, contradicting the traditional belief that fever in PE is primarily associated with these complications 1

Clinical Characteristics of Fever in PE

• Low-grade fever is present in approximately 14% of patients with PE who have no other identifiable source of fever 1

• High fever (temperature >39°C) can occur early in the course of PE, though it is less common than low-grade fever 4, 5

• Fever may persist for up to a week, but temperatures exceeding 38.5°C beyond six days should prompt investigation for other causes 4

• Patients with PE and fever tend to be younger and have a higher incidence of smoking compared to those without fever 2

Clinical Significance and Outcomes

• Fever in PE is associated with higher morbidity, including:

  • Increased likelihood of requiring intensive care admission (69.5% vs 35.7%) 2
  • Longer hospital length of stay (19.80 vs 12.20 days) 2
  • Higher requirement for mechanical ventilation (30.5% vs 6.6%) 2

• Patients with PE and fever have higher clot burden, with increased incidence of:

  • Massive and submassive PE (55.9% vs 36.8%) 2
  • Deep vein thrombosis (33.3% vs 17.4%) 2

• Higher in-hospital mortality has been observed in PE patients with fever compared to those without fever (22.0% vs 10.4%) 2

Diagnostic Considerations

• Fever should not deter clinicians from considering PE in the differential diagnosis, especially in patients with risk factors such as bed confinement 4, 5

• PE can be masked by pneumonia, particularly in patients with predominant systemic symptoms like fever 6

• Fever persisting beyond six days, especially with temperatures over 38.5°C, should prompt investigation for causes other than PE 4

Common Pitfalls and Caveats

• Mistaking PE for pneumonia due to overlapping clinical features, especially when fever is a prominent symptom 6

• Failing to consider PE in patients with unexplained fever, particularly in those with risk factors for venous thromboembolism 5

• Attributing persistent high fever solely to PE without excluding other causes, especially when fever lasts beyond six days 4

• Overlooking the possibility of PE in patients who initially respond to antibiotics for presumed pneumonia but subsequently deteriorate 6