Ali S. Raja, MD; Jeffrey O. Greenberg, MD; Amir Qaseem, MD, PhD, MHA; Thomas D. Denberg, MD, PhD; Nick Fitterman, MD; Jeremiah D. Schuur, MD, MHS; for the Clinical Guidelines Committee of the American College of Physicians *
Note: Best practice advice papers are “guides” only and may not apply to all patients and all clinical situations. Thus, they are not intended to override clinicians' judgment. All ACP best practice advice papers are considered automatically withdrawn or invalid 5 years after publication or once an update has been issued.
Disclaimer: The authors of this article are responsible for its contents, including any clinical or treatment recommendations.
Financial Support: Financial support for the development of this paper comes exclusively from the ACP operating budget.
Disclosures: Dr. Fitterman reports that he chairs the Test-Writing Committee for the secure examination of the American Board of Internal Medicine. Dr. Schuur reports that he chaired the Quality and Performance Committee of the American College of Emergency Physicians, in which capacity he helped to develop performance measures of appropriate use of computed tomography for pulmonary embolism. Authors not named here have disclosed no conflicts of interest. Authors followed the policy regarding conflicts of interest described at www.annals.org/article.aspx?articleid=745942. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-1772. A record of conflicts of interest is kept for each Clinical Guidelines Committee meeting and conference call and can be viewed at www.acponline.org/clinical_information/guidelines/guidelines/conflicts_cgc.htm.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Requests for Single Reprints: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.
Current Author Addresses: Dr. Raja: Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114.
Drs. Greenberg and Schuur: Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.
Dr. Qaseem: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.
Dr. Fitterman: Hofstra North Shore Long Island Jewish School of Medicine, 270 Park Avenue, Huntington, NY 11743.
Dr. Denberg: Carilion Clinic, PO Box 13727, Roanoke, VA 24036.
Author Contributions: Conception and design: A.S. Raja, J.O. Greenberg, A. Qaseem, T.D. Denberg, N. Fitterman, J.D. Schuur.
Analysis and interpretation of the data: A.S. Raja, A. Qaseem, T.D. Denberg.
Drafting of the article: A.S. Raja, J.O. Greenberg, A. Qaseem, T.D. Denberg, N. Fitterman, J.D. Schuur.
Critical revision of the article for important intellectual content: A.S. Raja, J.O. Greenberg, A. Qaseem, T.D. Denberg, J.D. Schuur.
Final approval of the article: A.S. Raja, J.O. Greenberg, A. Qaseem, T.D. Denberg, N. Fitterman, J.D. Schuur.
Provision of study materials or patients: T.D. Denberg.
Statistical expertise: A. Qaseem, T.D. Denberg.
Obtaining of funding: A. Qaseem, T.D. Denberg.
Administrative, technical, or logistic support: A.S. Raja, A. Qaseem, T.D. Denberg, J.D. Schuur.
Collection and assembly of data: A.S. Raja, J.O. Greenberg, T.D. Denberg.
Pulmonary embolism (PE) can be a severe disease and is difficult to diagnose, given its nonspecific signs and symptoms. Because of this, testing patients with suspected acute PE has increased dramatically. However, the overuse of some tests, particularly computed tomography (CT) and plasma d-dimer measurement, may not improve care while potentially leading to patient harm and unnecessary expense.
The literature search encompassed studies indexed by MEDLINE (1966–2014; English-language only) and included all clinical trials and meta-analyses on diagnostic strategies, decision rules, laboratory tests, and imaging studies for the diagnosis of PE. This document is not based on a formal systematic review, but instead seeks to provide practical advice based on the best available evidence and recent guidelines. The target audience for this paper is all clinicians; the target patient population is all adults, both inpatient and outpatient, suspected of having acute PE.
Clinicians should use validated clinical prediction rules to estimate pretest probability in patients in whom acute PE is being considered.
Clinicians should not obtain d-dimer measurements or imaging studies in patients with a low pretest probability of PE and who meet all Pulmonary Embolism Rule-Out Criteria.
Clinicians should obtain a high-sensitivity d-dimer measurement as the initial diagnostic test in patients who have an intermediate pretest probability of PE or in patients with low pretest probability of PE who do not meet all Pulmonary Embolism Rule-Out Criteria. Clinicians should not use imaging studies as the initial test in patients who have a low or intermediate pretest probability of PE.
Clinicians should use age-adjusted d-dimer thresholds (age × 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years to determine whether imaging is warranted.
Clinicians should not obtain any imaging studies in patients with a d-dimer level below the age-adjusted cutoff.
Clinicians should obtain imaging with CT pulmonary angiography (CTPA) in patients with high pretest probability of PE. Clinicians should reserve ventilation–perfusion scans for patients who have a contraindication to CTPA or if CTPA is not available. Clinicians should not obtain a d-dimer measurement in patients with a high pretest probability of PE.
Appendix Table 1. Wells Prediction Rule for Pretest Probability of PE*
Appendix Table 2. Revised Geneva Score for Predicting Pretest Probability of PE*
Table 1. Pulmonary Embolism Rule-Out Criteria for Predicting Probability of Pulmonary Embolism in Patients With Low Pretest Probability*
Pathway for the evaluation of patients with suspected PE.
PE = pulmonary embolism; PERC = Pulmonary Embolism Rule-Out Criteria.
* Using either a clinical decision tool or gestalt.
Table 2. Suggestions for Imaging in Patients With Suspected PE
Summary of the American College of Physicians best practice advice for the evaluation of patients with suspected acute pulmonary embolism.
CT = computed tomography; CTPA = computed tomographic pulmonary angiography; ELISA = enzyme-linked immunosorbent assay; PE = pulmonary embolism; V/Q = ventilation–perfusion.
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Ethan F. Kuperman, MD, MSc
University of Iowa
October 5, 2015
To the editor: I welcome the clarity that Raja and colleagues(1) bring to evaluating patients with suspected pulmonary embolism (PE), but I am not confident about applying their conclusions to my own hospitalist practice. I am specifically concerned about using “validated clinical prediction tools” in estimating PE risk in the hospital setting. There is currently no convincing evidence supporting use of the Wells criteria, the Geneva score, or the pulmonary embolism rule-out criteria (PERC) for inpatients.While the Wells score was originally derived from both inpatients and outpatients, more contemporary attempts to validate the criteria have unacceptably high failure rates in risk stratification for pulmonary embolism.(2) Kline and colleagues, cited by the guidelines authors, found a 6.8% probability of PE in inpatients with Wells score < 4 and a D-dimer < 500ng/mL.(3) This is too high for many clinicians to forego further testing. Likewise, the derivation and validation of the revised Geneva score was in the outpatient setting.(4) There are little data to support use of either for hospitalized patients. The PERC were developed for outpatient use and the majority of validation trials have been in the same setting, including every trial cited in the meta-analysis cited in the guidelines.(5) At this time, there is insufficient information to determine whether inpatients can safely be “ruled-out” based on these criteria. I am concerned that applying outpatient-derived data to manage inpatients may lead to flawed decision making. Although hospitalists need guidance on this very common and difficult clinical question, more primary data is needed to support a compelling inpatient practice guideline. 1. Raja AS, Greenberg JO, Qaseem A, Denberg TD, Fitterman N, Schuur JD. Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of PhysiciansEvaluation of Patients With Suspected Acute Pulmonary Embolism. Annals of Internal Medicine. 2015;N/A(N/A):N/A-N/A.2. Posadas-Martínez ML, Vázquez FJ, Giunta DH, Waisman GD, de Quirós FGB, Gándara E. Performance of the Wells score in patients with suspected pulmonary embolism during hospitalization: a delayed-type cross sectional study in a community hospital. Thrombosis research. 2014;133(2):177-81.3. Kline JA, Hogg MM, Courtney DM, Miller CD, Jones AE, Smithline HA. D‐dimer threshold increase with pretest probability unlikely for pulmonary embolism to decrease unnecessary computerized tomographic pulmonary angiography. Journal of Thrombosis and Haemostasis. 2012;10(4):572-81.4. Le Gal G, Righini M, Roy P-M, Sanchez O, Aujesky D, Bounameaux H, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Annals of Internal Medicine. 2006;144(3):165-71.5. Singh B, Mommer SK, Erwin PJ, Mascarenhas SS, Parsaik AK. Pulmonary embolism rule-out criteria (PERC) in pulmonary embolism—revisited: A systematic review and meta-analysis. Emergency Medicine Journal. 2013;30(9):701-6.
Payal Dinesh Parikh MD, Laura Rees Willett MD, Levi Sokol MD
Rutgers, Robert Wood Johnson Medical School
November 27, 2015
Letter to the Editor Annals of Internal Medicine re: ACP Clinical Guidelines on evaluation of patients with suspected PE.
We read Raja and colleagues’ guidelines (1) with interest.Regarding Best Practice Advice 6, we feel that the authors should support a more nuanced decision about ventilation/perfusion (V/Q) imaging for PE, rather than preferring CT pulmonary angiography (CTPA) in all situations except when absolutely contraindicated or not available. Particularly in patients with underlying normal lungs, V/Q scans provide a similar level of diagnostic accuracy and safety as CTPA (2,3), with an excellent negative predictive value. In contrast to its similar benefit, CTPA may confer greater harm from radiation exposure, false positives, incidental findings, and contrast exposure. The most important benefit of V/Q, particularly to younger patients, is the level of radiation exposure. CTPA delivers a dose of radiation to the female breast around 20 times that of VQ scan, and is thought to lead to a lifetime risk of breast or lung malignancy of more than 1 in 1,000 in younger women (4). In a randomized trial of CTPA vs. V/Q scanning (2), as many as one quarter of CTPA-diagnosed PEs were felt to be false-positive diagnoses. A diagnosis of PE generally leads to systemic anticoagulation, sometimes indefinitely, with all its attendant risks. A third important harm of CTPA is its greater likelihood of incidental findings, many of which lead to more imaging and radiation exposure. CTPA also involves exposure to IV contrast, with occasional severe toxicity.In light of this risk-benefit exploration, we feel that V/Q scan is actually the imaging test of choice in certain populations of patients with suspected PE, particularly younger patients with underlying normal lungs. An ER protocol advising a V/Q scan instead to CTPA for patients with normal chest X-rays resulted in a marked decrease in mean radiation exposure (7.2 mSv to 4.9 mSv) for women aged less than 40 years receiving imaging for PE (3). Finally, the authors state regarding pregnant patients, “although CT exposes these patients to less radiation than V/Q imaging doses, it may have teratogenic effects…” We suggest that while the fetus is exposed to slightly more radiation when using V/Q scintigraphy, the mother is exposed to a much higher dose of radiation from CTPA (4). There is also evidence that V/Q scanning is substantially more likely to be definitive in pregnant patients as opposed to CTPA (96% vs. 64%), possibly because of increased vena cava blood flow (5).References:1. Raja AS, Greenberg JO, Qaseem A, Denberg TD, Fitterman N, Schuur JD, et al. Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015; 163(9):701-711.2. Anderson DR, Kahn SR, Rodger MA, Kovacs MJ, Morris T, Hirsch A, et al. Computer tomographic pulmonary angiography versus ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007; 298:2743-53.3. Stein EG, Haramati LB, Chamarthy M, Sprayregen S, Davitt MM, Freeman LM. Success of a Safe and Simple Algorithm to Reduce Use of CT Pulmonary Angiography in the Emergency Department. American Journal of Roentgenol; 2010;194:392-397. 4. Sadigh G, Kelly AM, Cronin P. Challenges, controversies, and hot topics in pulmonary embolism imaging. AJR Am J Roentgenol; 2011;196:497-515.5. Ridge CA, McDermott S, Freyne BJ, Brennan DJ, Collins CD, Skehan SJ. Pulmonary embolism in pregnancy: Comparison of pulmonary CT angiography and lung scintigraphy. AJR Am J Roentgenol. 2009;193:1223-1227].
Raja AS, Greenberg JO, Qaseem A, et al, for the Clinical Guidelines Committee of the American College of Physicians. Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015;163:701–711. [Epub ahead of print 29 September 2015]. doi: https://doi.org/10.7326/M14-1772
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Published: Ann Intern Med. 2015;163(9):701-711.
Published at www.annals.org on 29 September 2015
Emergency Medicine, Guidelines, High Value Care, Hospital Medicine, Pulmonary Embolism.
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