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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