PaCO2–EtCO2 gradient and D-dimer in the diagnosis of suspected pulmonary embolism


Departments of Emergency Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


Background: The diagnosis of pulmonary embolism (PE) because of nonspecific clinical presentation remains as a challenge for emergency physicians. Arterial to end-tidal partial pressure of carbon dioxide (P(a-Et)CO2) gradient may be useful in the evaluation of PE. This aimed to define the diagnostic role of P(a-Et)CO2 gradient by sidestream capnography, as a noninvasive method, and D-dimer in patients with PE. Materials and Methods: Two hundred and three patients with chest pain or dyspnea who attend the hospital emergency ward were enrolled over a study period at a single academic center. PE was confirmed by multidetector computed tomography (MDCT) scans. PaCO2, EtCO2, and D-dimer were measured within 24 h of MDCT by capnograph. Results: The combination of P(a-Et)CO2 gradient (cutoff >9.2 ng/ml) and D-dimer (cutoff >3011 ng/ml) with sensitivity and specificity of 30.2% and 87.2% showed a significant diagnostic value in detecting PE (area under the curve = 0.577, P = 0.045) but not alone (P > 0.05). Conclusion: As the results show, the combination of P(a-Et)CO2 gradient and D-dimer can show an acceptable diagnostic value in detecting PE, although it suggests further research on evaluating the diagnostic value of P(a-Et)CO2 gradient and combining it with other diagnostic criteria to achieve a definite and generalizable result.


Rubini G, Ferrari C, Cimino A, Fanelli M, Altini C, Gaudiano A, et al. How often suspected pulmonary embolism is diagnosed and its main diagnostic characteristics, in an emergency nuclear medicine service? Four years experience. Hell J Nucl Med 2019;22:187-93.  Back to cited text no. 1
Pelletier-Galarneau M, Zannier E, Zuckier LS, Le Gal G. Referral patterns and diagnostic yield of lung scintigraphy in the diagnosis of acute pulmonary embolism. Thrombosis. 2017;2017:1-6. doi: 10.1155/2017/1623868.  Back to cited text no. 2
Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014;35:3033-69, 3069a-3069k.  Back to cited text no. 3
Wendelboe AM, Raskob GE. Global burden of thrombosis: Epidemiologic aspects. Circ Res 2016;118:1340-7.  Back to cited text no. 4
Pollack CV, Schreiber D, Goldhaber SZ, Slattery D, Fanikos J, O'Neil BJ, et al. Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: Initial report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol 2011;57:700-6.  Back to cited text no. 5
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;163:701-11.  Back to cited text no. 6
Remy-Jardin M. Are we overdiagnosing pulmonary embolism? “No”. J Thoracic Imaging 2018;33:348-9.  Back to cited text no. 7
Bozorgmehr R, Pishgahi M, Mohaghegh P, Bayat M, Khodadadi P, Ghafori A. Relationship between thrombosis risk factors, clinical symptoms, and laboratory findings with pulmonary embolism diagnosis; A cross-sectional study. Arch Acad Emerg Med 2019;7:41.  Back to cited text no. 8
Kruger PC, Eikelboom JW, Douketis JD, Hankey GJ. Pulmonary embolism: Update on diagnosis and management. Med J Aust 2019;210:516-24.  Back to cited text no. 9
Bass AR, Fields KG, Goto R, Turissini G, Dey S, Russell LA. Clinical decision rules for pulmonary embolism in hospitalized patients: A systematic literature review and meta-analysis. Thromb Haemost 2017;117:2176-85.  Back to cited text no. 10
Adam SS, Key NS, Greenberg CS. D-dimer antigen: Current concepts and future prospects. Blood 2009;113:2878-87.  Back to cited text no. 11
Koch V, Biener M, Müller-Hennessen M, Vafaie M, Staudacher I, Katus HA, et al. Diagnostic performance of D-dimer in predicting venous thromboembolism and acute aortic dissection. Eur Heart J Acute Cardiovasc Care 2020:1-9. doi: 10.1177/2048872620907322.  Back to cited text no. 12
Takano Y, Sakamoto O, Kiyofuji C, Ito K. A comparison of the end-tidal CO2 measured by portable capnometer and the arterial P CO2 in spontaneously breathing patients. Respir Med 2003;97:476-81.  Back to cited text no. 13
Verschuren F, Liistro G, Coffeng R, Thys F, Roeseler J, Zech F, et al. Volumetric capnography as a screening test for pulmonary embolism in the emergency department. Chest 2004;125:841-50.  Back to cited text no. 14
Ishaaya E, Tapson VF. Advances in the diagnosis of acute pulmonary embolism. F1000Res. 2020;9:F1000 Faculty Rev-44. doi: 10.12688/f1000research. 21347.1.  Back to cited text no. 15
Hemnes AR, Newman AL, Rosenbaum B, Barrett TW, Zhou C, Rice TW, et al. Bedside end-tidal CO2 tension as a screening tool to exclude pulmonary embolism. Eur Respir J 2010;35:735-41.  Back to cited text no. 16
Ozdemir M, Sonmez BM, Yilmaz F, Yilmaz A, Duyan M, Komut S. Is bedside end-tidal CO2 measurement a screening tool to exclude pulmonary embolism in emergency department? J Clin Med Res 2019;11:696-702.  Back to cited text no. 17
Ozsu S, Abul Y, Yilmaz I, Ozsu A, Oztuna F, Bulbul Y, et al. Prognostic significance of PaO2/PaCO2 ratio in normotensive patients with pulmonary embolism. Clin Respir J 2012;6:104-11.  Back to cited text no. 18
Aminiahidashti H, Shafiee S, Zamani Kiasari A, Sazgar M. Applications of end-tidal carbon dioxide (ETCO2) monitoring in emergency department; A narrative review. Emerg (Tehran) 2018;6:e5.  Back to cited text no. 19
Riaz I, Jacob B. Pulmonary embolism in Bradford, UK: Role of end-tidal CO2 as a screening tool. Clin Med (Lond) 2014;14:128-33.  Back to cited text no. 20
Yüksel M, Pekdemir M, Yilmaz S, Yaka E, Kartal AG. Diagnostic accuracy of noninvasive end-tidal carbon dioxide measurement in emergency department patients with suspected pulmonary embolism84-90. Turk J Med Sci 2016;46:84-90.  Back to cited text no. 21
Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: The ADJUST-PE study. JAMA 2014;311:1117-24.  Back to cited text no. 22
Manara A, D'hoore W, Thys F. Capnography as a diagnostic tool for pulmonary embolism: A meta-analysis. Ann Emerg Med 2013;62:584-91.  Back to cited text no. 23
Sanchez O, Wermert D, Faisy C, Revel MP, Diehl JL, Sors H, et al. Clinical probability and alveolar dead space measurement for suspected pulmonary embolism in patients with an abnormal D-dimer test result. J Thromb Haemost 2006;4:1517-22.  Back to cited text no. 24
Rodger MA, Jones G, Rasuli P, Raymond F, Djunaedi H, Bredeson CN, et al. Steady-state end-tidal alveolar dead space fraction and D-dimer: Bedside tests to exclude pulmonary embolism. Chest 2001;120:115-9.  Back to cited text no. 25
Kline JA, Hogg MM, Courtney DM, Miller CD, Jones AE, Smithline HA, et al. D-dimer and exhaled CO2/O2 to detect segmental pulmonary embolism in moderate-risk patients. Am J Respir Crit Care Med 2010;182:669-75.  Back to cited text no. 26
Robert-Ebadi H, Glauser F, Planquette B, Moumneh T, Le Gal G, Righini M. Safety of multidetector computed tomography pulmonary angiography to exclude pulmonary embolism in patients with a likely pretest clinical probability. J Thromb Haemost 2017;15:1584-90.  Back to cited text no. 27
Yoon YH, Lee SW, Jung DM, Moon SW, Horn JK, Hong YS. The additional use of end-tidal alveolar dead space fraction following D-dimer test to improve diagnostic accuracy for pulmonary embolism in the emergency department. Emerg Med J 2010;27:663-7.  Back to cited text no. 28
Lim W, Le Gal G, Bates SM, Righini M, Haramati LB, Lang E, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: Diagnosis of venous thromboembolism. Blood Adv 2018;2:3226-56.  Back to cited text no. 29
van Es N, van der Hulle T, van Es J, den Exter PL, Douma RA, Goekoop RJ, et al. Wells rule and d-dimer testing to rule out pulmonary embolism: A systematic review and individual-patient data meta-analysis. Ann Intern Med 2016;165:253-61.  Back to cited text no. 30