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Fever in Acute Pulmonary Embolism^*

^* From the Henry Ford Heart and Vascular Institute (Drs. Stein, Afzal, Henry, and Villareal), Detroit, MI.

Correspondence to: Paul D. Stein, MD, FCCP, Henry Ford Health System, Cardiac Wellness Center, 6525 Second Ave, Detroit, MI 48202-3006; e-mail: pstein1{at}hfhs.org

	Abstract

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Background: Although fever has been reported in several case series of acute pulmonary embolism (PE), the extent to which fever may be caused by PE, and not associated disease, has not been adequately sorted out. Clarification of the frequency and severity of fever in acute PE may assist in achieving an accurate clinical impression, and perhaps avoid an inadvertent exclusion of the diagnosis.

Purpose: The purpose of this investigation is to evaluate the extent to which fever is caused by acute PE.

Methods: Patients participated in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). Temperature was evaluated among patients with angiographically proven PE. A determination of whether other causes of fever were present was based on a retrospective analysis of discharge summaries, PIOPED summaries, and a computerized list of all discharge diagnoses.

Results: Among patients with PE and no other source of fever, fever was present in 43 of 311 patients (14%). Fever in patients with pulmonary hemorrhage or infarction was not more frequent than among those with no pulmonary hemorrhage or infarction, 39 of 267 patients (15%) vs 4 of 44 patients (9%; not significant). Clinical evidence of deep venous thrombosis was often present in patients with PE and otherwise unexplained fever.

Conclusion: Low-grade fever is not uncommon in PE, and high fever, although rare, may occur. Fever need not be accompanied by pulmonary hemorrhage or infarction.

Key Words: fever • physical diagnosis • pulmonary embolism • temperature • thromboembolism

	Introduction

TOP Abstract Introduction Materials and Methods Results Discussion References

 
The extent to which fever may be caused by pulmonary embolism (PE), and not associated disease, has not been adequately sorted out. Clarification of the frequency and severity of fever in acute PE may assist in achieving an accurate clinical impression and perhaps avoid an inadvertent exclusion of the diagnosis. The purpose of this investigation, therefore, is to evaluate the extent to which fever is caused by PE.

	Materials and Methods

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Data are from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED).¹ PIOPED was a prospective investigation of patients with suspected acute PE who were randomized for obligatory pulmonary angiography. In addition, there was an arm of the study that prospectively analyzed data from patients referred for pulmonary angiography because of suspected acute PE (nonrandomized patients). Data are from the arm of the study in which patients were randomly selected for pulmonary angiography, as described in the original PIOPED publication, and also from patients who were in the arm referred for pulmonary angiography. The latter group was not included in the original PIOPED publication. Only patients with PE shown by pulmonary angiography are included in the present study. There were 383 patients with PE diagnosed by pulmonary angiography. Temperature was recorded in 363 of these patients. Temperature was measured on the day of recruitment into PIOPED. Symptoms of PE began within 24 h of study entry.¹

Fever was defined as temperature of 37.8°C ( 100.0°F).^{2 3} Although the normal temperature in human beings has been said to be 37°C (98.6°F) on the basis of Wunderlich’s original observations > 120 years ago, the maximal oral temperature in normal individuals at 4:00 PM is 37.7°C (99.9°F).^{2 3}

A determination of whether other causes of fever were present was based on a retrospective analysis of discharge summaries, PIOPED summaries, and a computerized list of all discharge diagnoses. Information was not available in six patients, and these patients were eliminated from the group with no other possible or definite cause of fever. Among the patients with PE who had fever, possible or definite other causes of fever are listed in Table 1 .⁴ Patients having a sputum specimen with a positive Gram’s stain showing bacteria or a sputum culture showing growth of bacteria were considered to have pneumonia in addition to PE. These criteria are recognized to have an uncertain yield because of contamination by oropharyngeal flora.⁵ Whether some patients had transtracheal aspiration, catheter-brush sampling, or other advanced diagnostic techniques to limit contamination of the culture is not known. Only four patients with fever, however, were excluded because a diagnosis of pneumonia was made by Gram’s stain or sputum culture (Table 1) .

Patients were defined as having the pulmonary hemorrhage or infarction syndrome it they had hemoptysis, pleuritic pain, or atelectasis or parenchymal abnormality on the chest radiograph. The clinical distinction between pulmonary hemorrhage and pulmonary infarction among patients with PE depends on the rate of resolution of the radiographic opacity.⁶ A rapidly clearing radiodensity represents clearing of pulmonary hemorrhage. Progression of the hemorrhage to infarction is shown by organization of the radiodensity, which remains visible as an atelectatic streak or pleural thickening.⁶

Statistical Analysis
Comparisons were made by ² test. A p < 0.05 was considered significant. A 95% confidence interval (CI) was determined for each prevalence from the normal approximation to the binomial distribution.

	Results

TOP Abstract Introduction Materials and Methods Results Discussion References

 
All Patients
Fever was present in 95 of 363 patients (26%; 95% CI, 22 to 31%) with PE. Other causes of fever may have been present among these patients (Table 1) . The distribution of temperatures and the relation to pulmonary hemorrhage or infarction are shown in Table 2 . Among those with pulmonary hemorrhage or infarction, fever was present in 80 of 308 patients (26%; 95% CI, 21 to 31%) vs 15 of 55 patients (27%; 95% CI, 16 to 41%; not significant) among those who did not have pulmonary hemorrhage or infarction.

Fever was present in 43 of 311 patients (14%; 95% CI, 10 to 18%). The distribution of temperatures and relation to pulmonary hemorrhage or infarction are shown in Table 3 .

Signs or symptoms compatible with deep venous thrombosis were present in 24 of 43 patients (56%) with PE who had fever. Among patients with a temperature 38.9°C ( 102°F), three of five patients (60%) had clinical evidence compatible with deep venous thrombosis. Each of the four patients with PE and otherwise unexplained fever who did not have pulmonary hemorrhage or infarction had clinical evidence compatible with deep venous thrombosis.

	Discussion

TOP Abstract Introduction Materials and Methods Results Discussion References

 
Among patients with PE in whom recognized causes of fever were eliminated, 86% were afebrile. Among those with fever, the fever was usually low grade. Temperature 38.3°C ( 101°F) occurred in only 6% of such patients, and only 2% had a temperature of 38.9°C ( 102°F). Fever was not more frequent in patients with pulmonary hemorrhage or infarction than in those without.

Signs or symptoms compatible with deep venous thrombosis were frequently present among patients with PE who had fever, especially those who did not have pulmonary hemorrhage or infarction. The clinical diagnosis of deep venous thrombosis, however, has been demonstrated by numerous studies to be unreliable.⁷

Some conditions causing fever may not have been listed in the discharge summaries or computer listing of discharge diagnoses. The frequency of fever caused by PE, therefore, may be lower than we report.

Several case series reported the temperature in patients with acute PE, but whether the fever was caused by the PE or associated disease was not clarified. Among patients with PE, most of whom died, a low-grade fever was reported in 37%.⁸ Some suggested that low-grade fever, especially after an operation, is occasionally the only symptom of PE.⁹ Some reported that unless concomitant pulmonary infection is present, the temperature generally is 38.3°C ( 101°F).^{10 11} Higher temperatures generally were observed in patients with extensive pulmonary infarction or in whom secondary pneumonitis had developed distal to the embolus.¹¹ Occasional case reports describe PE as a cause of fever of undetermined origin.^{12 13}

In PIOPED among patients with PE and no prior cardiopulmonary disease, a temperature > 38.5°C (> 101.3°F) occurred in 7%.¹⁴ No attempt was made to eliminate patients with other causes of fever. Among patients with no prior cardiopulmonary disease who had the pulmonary infarction syndrome, temperature was > 38.5°C (> 101.3°F) in 6%.¹⁵ Among patients with PE who presented with the syndrome of isolated dyspnea, 16% had such a temperature elevation.¹⁵ As in the prior investigation, no attempt was made to eliminate patients with other causes of fever.

In the Urokinase Pulmonary Embolism Trial or the Urokinase-Streptokinase Embolism Trial, among patients with no prior cardiopulmonary disease, a temperature > 37.5°C (> 99.9°F) was observed in 50%.¹⁶ The prevalence of fever was the same among patients with massive and with submassive PE. At a tertiary care hospital, among all patients with PE diagnosed by pulmonary angiography between 1980 and 1984, 14% had a temperature > 37.8°C (> 100°F).¹⁷ Other causes of fever were not excluded in any of these case series.

Murray and associates ¹⁸ attempted to clarify whether fever in PE was caused by the PE or accompanying disease. Among patients with angiographically diagnosed PE and no other apparent cause of fever, a temperature of 38°C ( 100.4°F) was observed in 20 of 31 patients (64%), and 2 of 31 patients (6%) had a temperature of 39.5°C ( 103.1°F).¹⁸ Pulmonary infarction was not more frequent among patients with fever,¹⁸ and our observations are in agreement. Our observations are also in agreement with others who found temperatures > 38.3°C (> 101°F) only in patients with pulmonary infarction or secondary pneumonitis,^{10 11} although the apparent difference between the frequency of such a temperature elevation in patients with pulmonary hemorrhage or infarction and patients with no hemorrhage or infarction was not statistically significant.

In conclusion, although most patients with PE are afebrile, a low-grade fever may occur, and, rarely, even a high fever may occur. Fever occurs in patients without pulmonary infarction as well as in those with pulmonary infarction.

	Footnotes

 
Abbreviations: CI = confidence interval; PE = pulmonary embolism; PIOPED = Prospective Investigation of Pulmonary Embolism Diagnosis

Received for publication May 5, 1999. Accepted for publication July 15, 1999.

	References

TOP Abstract Introduction Materials and Methods Results Discussion References

 

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This Article Abstract Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Stein, P. D. Articles by Villareal, C. G. Search for Related Content PubMed PubMed Citation Articles by Stein, P. D. Articles by Villareal, C. G.