What is the pathophysiology behind increased fever in pulmonary embolism (PE)?

Pathophysiology of Fever in Pulmonary Embolism

Fever in pulmonary embolism is primarily caused by an inflammatory response triggered by massive infiltrates of inflammatory cells in the right ventricular myocardium, which occurs as a result of PE-induced "myocarditis" and excessive neurohumoral activation. 1

Inflammatory Mechanisms Behind PE-Associated Fever

The pathophysiological basis of fever in pulmonary embolism involves several interconnected mechanisms:

1. PE-Induced "Myocarditis"

   • Massive infiltrates of inflammatory cells have been found in the right ventricular myocardium of patients who died within 48 hours of acute PE 1
   • This inflammatory response is triggered by high levels of epinephrine released due to the stress response to PE 1

2. Neurohumoral Activation

   • The abrupt increase in pulmonary vascular resistance (PVR) leads to RV dilation and increased wall tension 1
   • This triggers excessive neurohumoral activation as a compensatory mechanism 1
   • The combination of abnormal RV wall tension and circulatory shock drives this inflammatory cascade 1

3. Thromboinflammatory Response

   • The presence of thromboemboli in the pulmonary arterial bed triggers local and systemic inflammatory responses 1
   • Thromboxane A2 and serotonin release contribute to vasoconstriction and inflammatory signaling 1

Clinical Characteristics of Fever in PE

Research evidence shows that fever in PE has distinct clinical patterns:

• Fever occurs in approximately 14% of patients with PE who have no other source of fever 2
• Fever can range from low-grade to high-grade (>39°C) in some cases 3
• PE-associated fever is more common in younger patients (average age 52.5 vs 58.7 years in non-febrile PE) 4
• Smokers have a higher incidence of fever with PE (44.1% vs 20.9%) 4

Relationship Between Fever and PE Severity

The presence of fever in PE correlates with disease severity and outcomes:

• Patients with fever are more likely to have massive and submassive PE (55.9% vs 36.8%) 4
• Higher clot burden is associated with fever in PE 4
• Higher incidence of deep vein thrombosis (33.3% vs 17.4%) is seen in patients with PE and fever 4
• Fever in PE is associated with increased morbidity:
  • Higher ICU admission rates (69.5% vs 35.7%) 4
  • Longer hospital stays (19.8 days vs 12.2 days) 4
  • Greater need for mechanical ventilation (30.5% vs 6.6%) 4
  • Higher in-hospital mortality (22.0% vs 10.4%) 4

Important Clinical Considerations

• Fever may persist despite antibiotic treatment when PE is the underlying cause 5, 6
• Resolution of fever typically occurs after appropriate anticoagulation therapy 5
• Fever does not necessarily indicate pulmonary infarction or hemorrhage 2
• PE should be considered in the differential diagnosis of unexplained fever, especially in bedridden patients 3

Diagnostic Pitfalls

• PE can be misdiagnosed as pneumonia due to overlapping symptoms, particularly when fever is prominent 6
• The presence of fever may lead clinicians away from considering PE as a diagnosis 5
• Initial improvement with antibiotics followed by clinical deterioration should raise suspicion for concurrent PE 6

Understanding the inflammatory basis of fever in PE is crucial for accurate diagnosis and timely management, as fever in PE is associated with higher morbidity, mortality, and clot burden.