Systematic review and meta-analysis of strategies for the diagnosis of suspected pulmonary embolism

Abstract Objectives To assess the likelihood ratios of diagnostic strategies for pulmonary embolism and to determine their clinical application according to pretest probability. Data sources Medline, Embase, and Pascal Biomed and manual search for articles published from January 1990 to September 2003. Study selection Studies that evaluated diagnostic tests for confirmation or exclusion of pulmonary embolism. Data extracted Positive likelihood ratios for strategies that confirmed a diagnosis of pulmonary embolism and negative likelihood ratios for diagnostic strategies that excluded a diagnosis of pulmonary embolism. Data synthesis 48 of 1012 articles were included. Positive likelihood ratios for diagnostic tests were: high probability ventilation perfusion lung scan 18.3 (95% confidence interval 10.3 to 32.5), spiral computed tomography 24.1 (12.4 to 46.7), and ultrasonography of leg veins 16.2 (5.6 to 46.7). In patients with a moderate or high pretest probability, these findings are associated with a greater than 85% post-test probability of pulmonary embolism. Negative likelihood ratios were: normal or near normal appearance on lung scan 0.05 (0.03 to 0.10), a negative result on spiral computed tomography along with a negative result on ultrasonography 0.04 (0.03 to 0.06), and a D-dimer concentration < 500 μg/l measured by quantitative enzyme linked immunosorbent assay 0.08 (0.04 to 0.18). In patients with a low or moderate pretest probability, these findings were associated with a post-test probability of pulmonary embolism below 5%. Spiral computed tomography alone, a low probability ventilation perfusion lung scan, magnetic resonance angiography, a quantitative latex D-dimer test, and haemagglutination D-dimers had higher negative likelihood ratios and can therefore only exclude pulmonary embolism in patients with a low pretest probability. Conclusions The accuracy of tests for suspected pulmonary embolism varies greatly, but it is possible to estimate the range of pretest probabilities over which each test or strategy can confirm or rule out pulmonary embolism.

[1]  Gordon H. Guyatt,et al.  Users' Guides to the Medical Literature: III. How to Use an Article About a Diagnostic Test A. Are the Results of the Study Valid? , 1994 .

[2]  G. Ferretti,et al.  Acute pulmonary embolism: role of helical CT in 164 patients with intermediate probability at ventilation-perfusion scintigraphy and normal results at duplex US of the legs. , 1997, Radiology.

[3]  A. van Rossum,et al.  Role of spiral volumetric computed tomographic scanning in the assessment of patients with clinical suspicion of pulmonary embolism and an abnormal ventilation/perfusion lung scan. , 1996, Thorax.

[4]  D. Slosman,et al.  Using clinical evaluation and lung scan to rule out suspected pulmonary embolism: Is it a valid option in patients with normal results of lower-limb venous compression ultrasonography? , 2000, Archives of Internal Medicine.

[5]  J. Heit,et al.  Operating characteristics of automated latex immunoassay fibrin D-dimer tests in the diagnosis of angiographically-defined acute pulmonary embolism. , 2000, Thrombosis and haemostasis.

[6]  M. Prins,et al.  Single-Detector Helical Computed Tomography as the Primary Diagnostic Test in Suspected Pulmonary Embolism: A Multicenter Clinical Management Study of 510 Patients , 2003, Annals of Internal Medicine.

[7]  V. Tapson,et al.  Clinical practice. The evaluation of suspected pulmonary embolism. , 2003, The New England journal of medicine.

[8]  G. Diamond,et al.  Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. , 1979, The New England journal of medicine.

[9]  M. Oudkerk,et al.  Comparison of contrast-enhanced magnetic resonance angiography and conventional pulmonary angiography for the diagnosis of pulmonary embolism: a prospective study , 2002, The Lancet.

[10]  D. Slosman,et al.  D-dimer testing for suspected pulmonary embolism in outpatients. , 1997, American journal of respiratory and critical care medicine.

[11]  H. Büller,et al.  A Comparative Study of Two Rapid D-dimer Tests for the Exclusion of Pulmonary Embolism in Symptomatic Patients , 2000, Thrombosis and Haemostasis.

[12]  D. Slosman,et al.  Plasma D-dimer in suspected pulmonary embolism: a comparison with pulmonary angiography and ventilation--perfusion scintigraphy. , 1990, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[13]  H. Büller,et al.  Ruling out clinically suspected pulmonary embolism by assessment of clinical probability and D-dimer levels: a management study , 2003, Thrombosis and Haemostasis.

[14]  J. Remy,et al.  Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique--comparison with pulmonary angiography. , 1992, Radiology.

[15]  P. Bossuyt,et al.  The clinical course of patients with suspected pulmonary embolism. , 1997, Archives of internal medicine.

[16]  P. Bossuyt,et al.  The Clinical Course of Patients With Suspected Pulmonary Embolism , 1997 .

[17]  M. Oudkerk,et al.  Comparison of a Quantitative Latex and a Quantitative ELISA Plasma D-Dimer Assay in the Exclusion of Segmental and Subsegmental Pulmonary Embolism , 2001, Thrombosis and Haemostasis.

[18]  G. Guyatt,et al.  Users' guides to the medical literature. , 1993, JAMA.

[19]  Haiyang Li,et al.  Determinants of plasma fibrin D-dimer sensitivity for acute pulmonary embolism as defined by pulmonary angiography. , 1999, Archives of pathology & laboratory medicine.

[20]  H. Büller,et al.  Use of a clinical decision rule in combination with D-dimer concentration in diagnostic workup of patients with suspected pulmonary embolism: a prospective management study. , 2002, Archives of internal medicine.

[21]  I. Kutinsky,et al.  Normal D-dimer levels in patients with pulmonary embolism. , 1999, Archives of internal medicine.

[22]  G. Guyatt,et al.  Users ' Guides to the Medical Literature : III . How to Use an Article About a Diagnostic Test : A . Are the Results of the Study Valid ? , 2022 .

[23]  V. Tapson,et al.  The Evaluation of Suspected Pulmonary Embolism , 2003 .

[24]  L. Pratali,et al.  Value of transthoracic echocardiography in the diagnosis of pulmonary embolism: results of a prospective study in unselected patients. , 2001, The American journal of medicine.

[25]  P. Investigators,et al.  Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). , 1990 .

[26]  J. Nunes.  D-dimers in diagnosis of pulmonary embolism , 2002, The Lancet.

[27]  J. Bodenhamer.  Value of the ventilation/perfusion scan in acute pulmonary embolism: Saltzman HA, Alavi A, Greenspan RH, et al JAMA 263:2753–2759 May 1990 , 1990 .

[28]  X Marchandise,et al.  Diagnosis of pulmonary embolism with spiral CT: comparison with pulmonary angiography and scintigraphy. , 1996, Radiology.

[29]  A. Panju,et al.  Does this patient have pulmonary embolism? , 2003, JAMA.

[30]  P. Douek,et al.  Dynamic contrast-enhanced MR angiography of pulmonary embolism: comparison with pulmonary angiography. , 1994, AJR. American journal of roentgenology.

[31]  D. Sackett,et al.  The architecture of diagnostic research , 2002, BMJ : British Medical Journal.

[32]  Burke,et al.  Diagnosis of Pulmonary Embolism D IAGNOSTIC R EASONING , 2007 .

[33]  W. Burdick.  Diagnosing pulmonary embolism in outpatients with clinical assessment, d-dimer measurement, venous ultrasound, and helical computed tomography: A multicenter management study , 2005 .

[34]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[35]  A. Alavi,et al.  Complications and Validity of Pulmonary Angiography in Acute Pulmonary Embolism , 1992, Circulation.

[36]  Daniel Hayoz,et al.  Diagnosing pulmonary embolism in outpatients with clinical assessment, D-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study. , 2004 .

[37]  G. Kovacs,et al.  Excluding Pulmonary Embolism at the Bedside without Diagnostic Imaging: Management of Patients with Suspected Pulmonary Embolism Presenting to the Emergency Department by Using a Simple Clinical Model and d-dimer , 2001, Annals of Internal Medicine.

[38]  H. Sostman,et al.  Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED). , 1996, American journal of respiratory and critical care medicine.

[39]  M. Prins,et al.  Diagnostic Strategies for Excluding Pulmonary Embolism in Clinical Outcome Studies , 2003, Annals of Internal Medicine.

[40]  A. Sing,et al.  The significance of venography in the management of patients with clinically suspected pulmonary embolism , 1991, Journal of internal medicine.

[41]  R B Haynes,et al.  Evidence base of clinical diagnosis: The architecture of diagnostic research , 2002 .

[42]  K. Mare,et al.  Pulmonary angiography: a safe procedure with modern contrast media and technique , 1998, European Radiology.

[43]  G. E. Newman,et al.  Pulmonary angiography with MR imaging: preliminary clinical experience. , 1993, Radiology.

[44]  M Gent,et al.  Use of a Clinical Model for Safe Management of Patients with Suspected Pulmonary Embolism , 1998, Annals of Internal Medicine.

[45]  S. Blacklow,et al.  Quantitative plasma D-dimer levels among patients undergoing pulmonary angiography for suspected pulmonary embolism. , 1993, JAMA.

[46]  K. Cederlund,et al.  A Comparison of Spiral Computed Tomography and Latex Agglutination D-dimer Assay in Acute Pulmonary Embolism using Pulmonary Arteriography as Gold Standard , 2002, Scandinavian cardiovascular journal : SCJ.

[47]  T L Chenevert,et al.  Diagnosis of pulmonary embolism with magnetic resonance angiography. , 1997, The New England journal of medicine.

[48]  H. Büller,et al.  The Use of a Rapid D-dimer Blood Test in the Diagnostic Workup for Pulmonary Embolism: A Management Study , 1999, Thrombosis and Haemostasis.

[49]  G. Briggs,et al.  Use of computed tomography pulmonary angiography in the diagnosis of pulmonary embolismin patients with an intermediate probability ventilation/perfusion scan , 2003, Internal medicine journal.

[50]  A. Greco,et al.  Diagnostic utility of echocardiography in patients with suspected pulmonary embolism. , 2003, The American journal of emergency medicine.

[51]  R. Dersimonian,et al.  Meta-analysis in the design and monitoring of clinical trials. , 1996, Statistics in medicine.

[52]  P. Grenier,et al.  Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study , 2002, The Lancet.

[53]  P. J. Drury,et al.  Acute pulmonary embolism: diagnosis with MR angiography. , 1999, Radiology.

[54]  A. Ragnarsson,et al.  Ultrasound at Scintigraphic “Intermediate Probability of Pulmonary Embolism” , 1996, Acta radiologica.

[55]  P. Travers,et al.  Pulmonary embolism in patients with intermediate probability lung scans: diagnosis with Doppler venous US and D-dimer measurement. , 1994, Radiology.

[56]  D. Slosman,et al.  Non-invasive diagnosis of venous thromboembolism in outpatients , 1999, The Lancet.

[57]  G. Raskob,et al.  Low-probability lung scan findings: a need for change. , 1991, Annals of internal medicine.

[58]  M. Oudkerk,et al.  Rapid ELISA Assay for Plasma D-Dimer in the Diagnosis of Segmental and Subsegmental Pulmonary Embolism , 2000, Thrombosis and Haemostasis.

[59]  G. ter Riet,et al.  Systematic reviews of evaluations of diagnostic and screening tests , 2001, BMJ : British Medical Journal.

[60]  J. T. ten Cate,et al.  Diagnostic Utility of Ultrasonography of Leg Veins in Patients Suspected of Having Pulmonary Embolism , 1997, Annals of Internal Medicine.

[61]  D. Slosman,et al.  Diagnosis of pulmonary embolism by a decision analysis-based strategy including clinical probability, D-dimer levels, and ultrasonography: a management study. , 1996, Archives of internal medicine.

[62]  A. Agresti,et al.  Order-restricted tests for stratified comparisons of binomial proportions. , 1996, Biometrics.

[63]  Carletta Demps.  Pulmonary embolism: Diagnosis with contrast-enhanced electron-beam CT and comparison with pulmonary angiography , 1996 .

[64]  D. Slosman,et al.  Contribution of noninvasive evaluation to the diagnosis of pulmonary embolism in hospitalized patients. , 1999, The European respiratory journal.

[65]  H. Büller,et al.  Feasibility, safety and clinical utility of angiography in patients with suspected pulmonary embolism , 2004, European Radiology.

[66]  A Vieillard-Baron,et al.  Pulmonary embolism detection: prospective evaluation of dual-section helical CT versus selective pulmonary arteriography in 157 patients. , 2000, Radiology.

[67]  D. Ost,et al.  The negative predictive value of spiral computed tomography for the diagnosis of pulmonary embolism in patients with nondiagnostic ventilation-perfusion scans. , 2001, The American journal of medicine.

[68]  L. Hirsch.  Competing interests: none declared. , 2006 .

[69]  Philip K. Bock.  Ethical Approval Not Required , 1994 .