46 – Do all emboli detected on cross-sectional imaging of the lung lead to the same degree of oxygenation compromise (hypoxia)?

46 – Do all emboli detected on cross-sectional imaging of the lung lead to the same degree of oxygenation compromise (hypoxia)?

Tyler Humphrey, Geno J. Merli, Stavros V. Konstantinides, Hany Bedair.

Response/Recommendation: While current evidence suggests that not all emboli detected on cross-sectional imaging of the lung result in the same degree of hypoxia, evidence is conflicting regarding the association between emboli size and location to the degree of patient hypoxia.  Providers should continue to risk-stratify patients with acute pulmonary embolism (PE) by hemodynamic status and right ventricular dysfunction in accordance with the European Society of Cardiology (ESC) 2019 and the American Society of Hematology (ASH) 2020 guidelines for management of venous thromboembolism (VTE).

Strength of Recommendation: Limited.

Rationale: Acute PE represents a common and potentially life-threatening medical problem for many patients worldwide1.  Current guidelines the ESC 2019, and the ASH 2020 for management of VTE recommend risk stratification for patients with PE based on hemodynamic status, right ventricular dysfunction, and certain laboratory markers2,3.  Nevertheless, the popularity of computed tomography pulmonary angiography (CTPA) as the first-line diagnostic test for PE has led to an increasing body of research attempting to correlate emboli characteristics seen on imaging to patient outcomes and prognosis4,5.

A large body of literature has described the correlation between increasing hypoxia – clinically described as partial pressure of oxygen (PaO2), percent saturation of oxygen (SpO2), alveolar-arterial (AA) oxygen gradient – and worsening outcomes following PE, despite these measures having low sensitivity for diagnosis6–10.  In established prognostic tools, such as the Pulmonary Embolism Severity Index (PESI), decreased PaO2 upon initial presentation is a predictor for higher 30-day mortality after acute PE11,12.  It has been described extensively that hypoxemia from acute PE results from ventilation/perfusion mismatch from redistribution of pulmonary blood flow, while minor contributors to hypoxemia include right ventricular failure, loss of pulmonary surfactant, and release of vasoconstrictive substances from nearby emboli9,10,13,14.

Many studies have attempted to correlate pulmonary embolus characteristics to clinical hypoxia parameters, given the latter’s correlation with mortality following PE.  Most research utilizes validated “clot scoring” indices, such as the validated Qanadli score, which requires a specialist radiologist to incorporate imaging findings of clot size and location to create an “obstructive index” score15.  Of note, while findings are mixed as to whether embolus obstructive index is an independent predictor of PE mortality, many studies, including a 2013 meta-analysis, show no correlation between embolus obstructive index and mortality13,15–23.

A few recent retrospective studies found that an increasing pulmonary artery obstructive index (PAOI) on initial CTPA was associated with increasing AA gradients, worsening PaO2, lower SpO2, and lower partial pressure of carbon dioxide (PaCO2)24–27.  Other studies, however, did not come to the same conclusions.  In three other recent retrospective studies, Lerche et al., and Rodrigues et al., found no association between the clot burden or obstructive index and PaO2 values, while another study by Nakada et al., found no association between embolus volume and PaO228–30.

Further research has attempted to understand the association between the location of the embolus and patient oxygenation measures.  While two recent studies found that central and proximal emboli were associated with lower PaO2 and higher AA gradients in patients compared to distal and peripheral emboli, another study found no correlation between thrombus vessel location and oxygenation parameters31–33.  Interestingly, Pulido et al., in a study of 13,133 patients, found no correlation between size and location of pulmonary emboli with severity of hypoxia34.  The mixed results from these studies reinforce the notion that while not all emboli appear to result in the same degree of hypoxia, the association is not well understood.  More prospective studies and meta-analyses are needed before further conclusions can be drawn.


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2.         Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv. 2020;4(19):4693-4738. doi:10.1182/bloodadvances.2020001830

3.         Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405

4.         Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest. 2002;121(3):877-905. doi:10.1378/chest.121.3.877

5.         Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008;29(18):2276-2315. doi:10.1093/eurheartj/ehn310

6.         Ozsu S, Abul Y, Yilmaz I, et al. Prognostic significance of PaO2/PaCO2 ratio in normotensive patients with pulmonary embolism. Clin Respir J. 2012;6(2):104-111. doi:10.1111/j.1752-699X.2011.00253.x

7.         Hsu JT, Chu CM, Chang ST, et al. Prognostic role of alveolar-arterial oxygen pressure difference in acute pulmonary embolism. Circ J Off J Jpn Circ Soc. 2006;70(12):1611-1616. doi:10.1253/circj.70.1611

8.         Jiménez D, Aujesky D, Moores L, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170(15):1383-1389. doi:10.1001/archinternmed.2010.199

9.         Bircan A, Karadeniz N, Ozden A, et al. A simple clinical model composed of ECG, shock index, and arterial blood gas analysis for predicting severe pulmonary embolism. Clin Appl Thromb Off J Int Acad Clin Appl Thromb. 2011;17(2):188-196. doi:10.1177/1076029609351877

10.       Petersson J, Glenny RW. Gas exchange and ventilation-perfusion relationships in the lung. Eur Respir J. 2014;44(4):1023-1041. doi:10.1183/09031936.00037014

11.       Zhou X-Y, Ben S-Q, Chen H-L, Ni S-S. The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis. Respir Res. 2012;13:111. doi:10.1186/1465-9921-13-111

12.       Agrawal N, Ramegowda RT, Patra S, et al. Predictors of inhospital prognosis in acute pulmonary embolism: keeping it simple and effective! Blood Coagul Fibrinolysis Int J Haemost Thromb. 2014;25(5):492-500. doi:10.1097/MBC.0000000000000093

13.       Furlan A, Aghayev A, Chang C-CH, et al. Short-term mortality in acute pulmonary embolism: clot burden and signs of right heart dysfunction at CT pulmonary angiography. Radiology. 2012;265(1):283-293. doi:10.1148/radiol.12110802

14.       Matsuoka S, Kurihara Y, Yagihashi K, Niimi H, Nakajima Y. Quantification of thin-section CT lung attenuation in acute pulmonary embolism: correlations with arterial blood gas levels and CT angiography. AJR Am J Roentgenol. 2006;186(5):1272-1279. doi:10.2214/AJR.05.0047

15.       Ceylan N, Tasbakan S, Bayraktaroglu S, et al. Predictors of clinical outcome in acute pulmonary embolism: Correlation of CT pulmonary angiography with clinical, echocardiography and laboratory findings. Acad Radiol. 2011;18(1):47-53. doi:10.1016/j.acra.2010.08.024

16.       Furlan A, Patil A, Park B, Chang C-CH, Roberts MS, Bae KT. Accuracy and reproducibility of blood clot burden quantification with pulmonary CT angiography. AJR Am J Roentgenol. 2011;196(3):516-523. doi:10.2214/AJR.10.4603

17.       Ghaye B, Ghuysen A, Willems V, et al. Severe pulmonary embolism:pulmonary artery clot load scores and cardiovascular parameters as predictors of mortality. Radiology. 2006;239(3):884-891. doi:10.1148/radiol.2392050075

18.       Jain CC, Chang Y, Kabrhel C, et al. Impact of Pulmonary Arterial Clot Location on Pulmonary Embolism Treatment and Outcomes (90 Days). Am J Cardiol. 2017;119(5):802-807. doi:10.1016/j.amjcard.2016.11.018

19.       Ghuysen A, Ghaye B, Willems V, et al. Computed tomographic pulmonary angiography and prognostic significance in patients with acute pulmonary embolism. Thorax. 2005;60(11):956-961. doi:10.1136/thx.2005.040873

20.       Meinel FG, Nance JW, Schoepf UJ, et al. Predictive Value of Computed Tomography in Acute Pulmonary Embolism: Systematic Review and Meta-analysis. Am J Med. 2015;128(7):747-759.e2. doi:10.1016/j.amjmed.2015.01.023

21.       Sardi A, Gluskin J, Guttentag A, Kotler MN, Braitman LE, Lippmann M. Saddle pulmonary embolism: is it as bad as it looks? A community hospital experience. Crit Care Med. 2011;39(11):2413-2418. doi:10.1097/CCM.0b013e31822571b2

22.       Soares TH, de Bastos M, de Carvalho BV, et al. Prognostic value of computed tomographic pulmonary angiography and the pulmonary embolism severity index in patients with acute pulmonary embolism. Blood Coagul Fibrinolysis Int J Haemost Thromb. 2013;24(1):64-70. doi:10.1097/MBC.0b013e32835a72c2

23.       Vedovati MC, Germini F, Agnelli G, Becattini C. Prognostic role of embolic burden assessed at computed tomography angiography in patients with acute pulmonary embolism: systematic review and meta-analysis. J Thromb Haemost JTH. 2013;11(12):2092-2102. doi:10.1111/jth.12429

24.       Karakayalı O, Yılmaz S, Ertok İ, et al. Correlation of alveolar–arterial gradient with Computed Tomography Pulmonary Artery Obstruction index in acute Pulmonary Embolism. Cumhur Med J. 2016;38(4):305-314. doi:10.7197/cmj.v38i4.5000188778

25.       Metafratzi ZM, Vassiliou MP, Maglaras GC, et al. Acute pulmonary embolism: correlation of CT pulmonary artery obstruction index with blood gas values. AJR Am J Roentgenol. 2006;186(1):213-219. doi:10.2214/AJR.04.1320

26.       Sen HS, Abakay Ö, Cetincakmak MG, et al. A single imaging modality in the diagnosis, severity, and prognosis of pulmonary embolism. BioMed Res Int. 2014;2014:470295. doi:10.1155/2014/470295

27.       Subramanian M, Ramadurai S, Arthur P, Gopalan S. Hypoxia as an independent predictor of adverse outcomes in pulmonary embolism. Asian Cardiovasc Thorac Ann. 2018;26(1):38-43. doi:10.1177/0218492317746252

28.       Lerche M, Bailis N, Akritidou M, Meyer HJ, Surov A. Pulmonary Vessel Obstruction Does Not Correlate with Severity of Pulmonary Embolism. J Clin Med. 2019;8(5):E584. doi:10.3390/jcm8050584

29.       Rodrigues B, Correia H, Figueiredo A, et al. [Clot burden score in the evaluation of right ventricular dysfunction in acute pulmonary embolism: quantifying the cause and clarifying the consequences]. Rev Port Cardiol Orgao Of Soc Port Cardiol Port J Cardiol Off J Port Soc Cardiol. 2012;31(11):687-695. doi:10.1016/j.repc.2012.02.020

30.       Nakada K, Okada T, Osada H, Honda N. Relation between pulmonary embolus volume quantified by multidetector computed tomography and clinical status and outcome for patients with acute pulmonary embolism. Jpn J Radiol. 2010;28(1):34-42. doi:10.1007/s11604-009-0380-x

31.       Alonso Martinez JL, Anniccherico Sánchez FJ, Urbieta Echezarreta MA, García IV, Álvaro JR. Central Versus Peripheral Pulmonary Embolism: Analysis of the Impact on the Physiological Parameters and Long-term Survival. North Am J Med Sci. 2016;8(3):134-142. doi:10.4103/1947-2714.179128

32.       Ghanima W, Abdelnoor M, Holmen LO, Nielssen BE, Sandset PM. The association between the proximal extension of the clot and the severity of pulmonary embolism (PE): a proposal for a new radiological score for PE. J Intern Med. 2007;261(1):74-81. doi:10.1111/j.1365-2796.2006.01733.x

33.       Irmak I, Sertçelik Ü, Öncel A, et al. Correlation of thrombosed vessel location and clot burden score with severity of disease and risk stratification in patients with acute pulmonary embolism. Anatol J Cardiol. 2020;24(4):247-253. doi:10.14744/AnatolJCardiol.2020.55013

34.       Pulido L, Grossman S, Smith EB, et al. Clinical presentation of pulmonary embolus after total joint arthroplasty: do size and location of embolus matter? Am J Orthop Belle Mead NJ. 2010;39(4):185-189.

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