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What Is the Best Imaging Study to Rule Out Pulmonary Embolism in Pregnancy?

       Take-Home Message

      Both computed tomography (CT) pulmonary angiography and lung scintigraphy (ie, ventilation-perfusion scan) are appropriate imaging options for exclusion of pulmonary embolism during pregnancy.

       Methods

       Data Sources

      MEDLINE and EMBASE databases were searched from inception through July 2015. The “related article” and “find similar” features were used to identify additional studies, and bibliographies of identified articles were scanned for further relevant articles. The search strategy included 3 sets of search terms including the condition (pulmonary embolism and venous thromboembolism), the subjects (pregnant patients), and the index tests. No language filters were applied.

       Study Selection

      Prospective and retrospective studies with consecutive patient enrollment with at least 25 subjects in which the provider suspected pulmonary embolism in pregnant patients were included. The Quality Assessment of Diagnostic Accuracy Studies-2
      • Whiting P.F.
      • Rutjes A.W.S.
      • Westwood M.E.
      • et al.
      QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies.
      tool was used to ascertain bias and included whether patient selection was consecutive, whether the index test was interpreted without knowledge of the reference standard, and whether the test was performed within 24 hours of patient presentation.

       Data Extraction and Synthesis

      Two authors independently extracted data with a standardized data collection form, and discrepancies were resolved by a third author. An inconclusive index test result was considered as a negative reference test result, but treatment for pulmonary embolism after an inconclusive index test result was considered as a positive reference test result. Heterogeneity was assessed by comparing clinical characteristics of the individual studies, such as previous testing and reported clinical decision rule results, stage of pregnancy, and type of imaging modality and technology used. Meta-analysis was not used because of the low methodological quality of the individual studies, as well as increased heterogeneity between the studies. Sensitivity and negative predictive values were calculated in each study and imaging modality, with the authors reporting the combined values as a median.

      Results

      Tabled 1Summary of results for the diagnosis of pulmonary embolism in pregnancy.
      Diagnostic Imaging ModalityMedian Sensitivity (Range), %Median Adjusted Sensitivity
      Sensitivity analysis performed: inconclusive test results assumed as positive.
      (Range), %
      Median Negative Predictive Value (Range), %
      CT pulmonary angiography83 (0–100)100 (80–100)100 (96–100)
      Lung scintigraphy100 (0–100)100 (100)100 (99–100)
      Sensitivity analysis performed: inconclusive test results assumed as positive.
      A total of 8,144 records were identified through database searching, of which 195 articles met initial screening criteria; of these, 11 studies (4 CT pulmonary angiography, 5 lung scintigraphy, and 2 both) with a total of 695 CT pulmonary angiography and 665 lung scintigraphy results were included. Lung scintigraphy was applied by different techniques, such as ventilation-perfusion scanning, perfusion-only scanning, and ventilation-perfusion single-photon-emission CT, which produces 3-dimensional images. The overall median prevalence of pulmonary embolism was 3.3% (range 0.0% to 8.7%). The median frequency of inconclusive results was 5.9% (range 0.9% to 36%) for CT pulmonary angiography and 4.0% (range 0% to 23%) for lung scintigraphy. Sensitivity and negative predictive values for both tests in this population were high (Table).

      Commentary

      Pregnant women have a 5-fold increased risk of venous thromboembolism compared with age-matched controls.
      • Pomp E.R.
      • Lenselink A.M.
      • Rosendaal F.R.
      • et al.
      Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study.
      Untreated, mortality is as high as 9%,
      • MacKAy A.P.
      • Berg C.J.
      • Liu X.
      • et al.
      Changes in pregnancy mortality ascertainment: United States, 1999-2005.
      but treating with heparin without confirming the diagnosis carries unnecessary morbidity as well. Therefore, being able to diagnose pulmonary embolism in pregnancy is important, although it is actually less common in this population than in nonpregnant patients with suspected pulmonary embolism.
      • Kline J.A.
      • Richardson D.M.
      • Than M.P.
      • et al.
      Systematic review and meta-analysis of pregnant patients investigated for suspected pulmonary embolism in the emergency department.
      CT pulmonary angiography has been considered the diagnostic criterion standard for many years; however, because of increased concerns about radiation exposure, lung scintigraphy has been recently recommended as an imaging option.
      This systematic review examined the ability of CT pulmonary angiography and lung scintigraphy to exclude the diagnosis of pulmonary embolism. In accordance with the heterogeneity of the data and the lack of head-to-head comparisons, the authors concluded that both CT pulmonary angiography and lung scintigraphy are appropriate for exclusion of pulmonary embolism during pregnancy.
      One key consideration not addressed in the current review is that of radiation exposure. The fetal dose from CT pulmonary angiography increases with gestational age, whereas that from lung scintigraphy decreases.
      • Motavalli R.L.
      • Azghadi H.E.
      • Hakimabad M.H.
      • et al.
      Pulmonary embolism in pregnant patients: assessing organ dose to pregnant phantom and its fetus during lung imaging.
      The Centers for Disease Control and Prevention uses a threshold of 0.05 Gy, or 5 rad, for fetal harm, and both the CT pulmonary angiography and lung scintigraphy deliver doses lower than 5 rad.

      Office of Public Health Preparedness and Response. Potential health effects (other than cancer) of prenatal radiation exposure. Available at: https://emergency.cdc.gov/radiation/prenatalphysician.asp. Accessed March 26, 2018.

      In aggregate, CT pulmonary angiography results in 3.4 to 6 times lower embryo and fetal radiation exposure, and in the first 2 trimesters may have 50% to 97% percent the radiation dose of lung scintigraphy.
      • Perisinakis K.
      • Seimenis I.
      • Tzedakis A.
      • et al.
      Perfusion scintigraphy versus 256-slice CT angiography in pregnant patients suspected of pulmonary embolism: comparison of radiation risks.
      From a practical standpoint, CT pulmonary angiography is generally more readily available in the ED and is read faster, with better interobserver agreement in interpretation compared with lung scintigraphy.
      • Revel M.P.
      • Cohen S.
      • Sanchez O.
      • et al.
      Pulmonary embolism during pregnancy: diagnosis with lung scintigraphy or CT angiography?.
      The Appropriate Use Criteria for Ventilation-Perfusion Imaging in Pulmonary Embolism working group
      • Waxman A.D.
      • Bajc M.
      • Brown M.
      • et al.
      Appropriate use criteria for ventilation-perfusion imaging in pulmonary embolism: summary and excerpts.
      offers additional practical pointers. For pregnant patients for whom pulmonary embolism is suspected and for whom the chest radiograph result is normal, lung scintigraphy is a good choice because it limits the radiation to the mother. If, on the other hand, the chest radiograph is grossly abnormal, then lung scintigraphy would not be appropriate because it would likely be inconclusive owing to the inherent mismatch. The ability of CT pulmonary angiography to elucidate an alternative diagnosis, which may occur up to 33% of the time, may also be beneficial.
      • Chen Y.A.
      • Gray B.G.
      • Bandiera G.
      • et al.
      Variation in the utilization and positivity rates of CT pulmonary angiography among emergency physicians at a tertiary academic emergency department.
      This review suggests that both CT pulmonary angiography and lung scintigraphy may be useful in the evaluation of suspected pulmonary embolism in the pregnant patient.

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        • Perisinakis K.
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