Clinical research study
Diagnostic Pathways in Acute Pulmonary Embolism: Recommendations of The PIOPED II Investigators

https://doi.org/10.1016/j.amjmed.2006.05.060Get rights and content

Abstract

Purpose

To formulate comprehensive recommendations for the diagnostic approach to patients with suspected pulmonary embolism, based on randomized trials.

Methods

Diagnostic management recommendations were formulated based on results of the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) and outcome studies.

Results

The PIOPED II investigators recommend stratification of all patients with suspected pulmonary embolism according to an objective clinical probability assessment. D-dimer should be measured by the quantitative rapid enzyme-linked immunosorbent assay (ELISA), and the combination of a negative D-dimer with a low or moderate clinical probability can safely exclude pulmonary embolism in many patients. If pulmonary embolism is not excluded, contrast-enhanced computed tomographic pulmonary angiography (CT angiography) in combination with venous phase imaging (CT venography), is recommended by most PIOPED II investigators, although CT angiography plus clinical assessment is an option. In pregnant women, ventilation/perfusion scans are recommended by many as the first imaging test following D-dimer and perhaps venous ultrasound. In patients with discordant findings of clinical assessment and CT angiograms or CT angiogram/CT venogram, further evaluation may be necessary.

Conclusion

The sequence for diagnostic test in patients with suspected pulmonary embolism depends on the clinical circumstances.

Section snippets

Clinical assessment

Physicians with experience in pulmonary embolism showed similar results with empirical assessment14, 17, 18 and by objective assessment (Table 3).2, 13, 14, 15, 16, 17, 19 Objective assessment may be more robust when applied by nonexperts.

Recommendations for clinical assessment:

  • Clinical assessment should be made before imaging.

  • Clinical assessment should be made by an objective method.

Patients with low probability clinical assessment

The quantitative rapid enzyme-linked immunosorbent assay (ELISA), with a sensitivity of 95%, showed the most clinically useful values among the various D-dimer assays.20 When used in combination with a low probability objective clinical assessment, which ranges from 4% to 15%2, 14, 15, 16, 17, 19 (Table 3, Figure 1), the post-test probability of pulmonary embolism ranges from 0.7% to 2% with a normal D-dimer rapid ELISA.20, 21 No further testing is required if D-dimer is normal in a patient

Patients with a Moderate Probability Clinical Assessment

Patients with objectively measured moderate clinical probabilities of pulmonary embolism were shown to have pulmonary embolism in 29% to 38%.2, 14, 15, 16, 17, 18, 21 The posttest probability of pulmonary embolism with a 30% clinical probability of pulmonary embolism is 5% with a normal rapid ELISA.20, 21

With a moderate clinical probability assessment, if the CT angiogram was negative, pulmonary embolism was present in 11%. If CT angiogram/CT venogram was negative, pulmonary embolism was

Patients with a high probability clinical assessment

A D-dimer is not helpful because a negative D-dimer does not exclude pulmonary embolism in >15% of patients with a high probability clinical assessment.20, 21

If either CT angiography alone or CT angiography/CT venography combination were positive in a patient with a high probability clinical assessment, pulmonary embolism was present in 96% in PIOPED II.1 If CT angiography was negative in a patient with a high probability assessment, pulmonary embolism was present in 40%, and if CT

Optional pathways, all patients

Venous ultrasound detects deep venous thrombosis in 13% to 15% of patients with suspected pulmonary embolism28, 29 and in 29% with proven pulmonary embolism,29 thereby allowing treatment with no further obligatory testing.

Recommendation for optional pathways:

  • A venous ultrasound before imaging with CT angiography or CT angiography/CT venography is optional and may guide treatment if positive.

Patients with allergy to iodinated contrast material

If clinical assessment and D-dimer fail to exclude pulmonary embolism, a venous ultrasound may be positive and guide therapy. Patients with mild to moderate iodine allergies may be pretreated with steroids and then imaged with CT. With severe iodine allergy, pulmonary scintigraphy may be a useful alternative. A low probability ventilation/perfusion scan combined with a low probability clinical assessment showed pulmonary embolism in only 4%.18 A high probability ventilation/perfusion scan in a

Patients with impaired renal function

In PIOPED II, only 1 of 824 patients who had CT angiography (0.1%) developed renal failure.1 Nonionic contrast material was used.1 Patients with abnormal serum creatinine levels were excluded. If the creatinine clearance is only somewhat elevated, whether to proceed with CT imaging depends on clinical judgment. Nonionic contrast material appears to be less nephrotoxic35 and generally better tolerated36 than ionic contrast material, although some reported no difference in nephrotoxicity.37

Women of reproductive age

Female breast radiation is a concern, but the risk of death from undiagnosed pulmonary embolism far exceeds the risk of radiation-induced malignancy. The absorbed dose to the breast with CT angiography has been calculated as 10-50 mGy.42, 43, 44 The absorbed dose to the breast with a perfusion lung scan has been estimated to be 0.28 mGy.42 The absorbed dose to the breast with standard 2-view mammography is 3 mGy.43

Pulmonary scintigraphy would minimize breast radiation. In PIOPED, a

Pregnant patients

In pregnant women, D-dimer testing may be useful even though it may be positive due to the pregnancy.45 Venous ultrasound detects deep venous thrombosis in 13% to 15% of patients with suspected pulmonary embolism28, 29 and in 29% with proven pulmonary embolism,29 eliminating the need for radiographic imaging. If radiographic imaging is necessary, some have recommended46 or used47 CT angiography rather than ventilation/perfusion lung scans. Magnetic resonance imaging requires further validation.

Patients in extremis

The sensitivity of transthoracic echocardiography for right ventricular enlargement or dysfunction in patients with massive pulmonary embolism or unstable patients, combining data from 3 case series, was 33 of 33 (100%).50, 51, 52 If any 2 of the following 3 assessments were positive (clinical probability high, echocardiogram and ultrasound), the sensitivity for massive pulmonary embolism was 33 of 34 (97%) and the negative predictive value was 98%.53

Recommendations for patients in extremis:

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    Supported by Grants HL63899, HL63928, HL63931, HL063932, HL63940, HL63941, HL63942, HL63981, HL63982, and HL67453 from the U.S. Department of Health and Human Services, Public Health Services, National Heart, Lung, and Blood Institute, Bethesda, MD.

    Diagnostic Pathways in Acute Pulmonary Embolism: Recommendations of the PIOPED II Investigators by Stein et al is being jointly published by The American Journal of Medicine and Radiology. A similar article will appear as an editorial in the January 2007 issue of Radiology.

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