Intermediate pulmonary embolism: Diagnosis and management
Authors: Davidson Bruce L 
Published: December 2019

Intermediate (“submassive”) pulmonary embolism (PE) is proven acute PE without shock but with elevated troponin, BNP, or NT-proBNP, with either contrast-enhanced chest CT or echocardiographic evidence for right ventricular (RV) dysfunction, usually enlargement. However, definitions of intermediate PE vary widely: Some allow a single abnormality of any of the five (two imaging; three biomarker) results, and some would accept normal findings in all five but ECG evidence of RV strain. The quite varied criteria means recommendations for intermediate PE management frequently are not derived from the same type of patient. Diagnosis: Intermediate PE is considered after a diagnostic CT PA-gram with filling defects. The imaging study RV:LV cavity dimensions can be measured in the same image, but a ratio >1.0 is not predictive for adverse outcomes. Abnormal interventricular septum position and reflux of IV contrast into the IVC are associated with poorer outcomes. Echocardiography can measure RV and LV cavity dimensions in the 4-chamber view, but measurements without echo contrast are unreliable. Dynamic views of the RV can show impaired contraction, and/or reduced tricuspid annular plane systolic excursion (TAPSE), and/or elevated estimated pulmonary artery systolic pressure. But in a recent study by expert investigators, 27/83 (33%) of patients presenting to the Emergency Department with persistent dyspnea but CT PA-grams negative for PE had RV dysfunction by one or more of these echocardiogram criteria. “RV dysfunction” is prevalent in dyspneic patients; in the acute PE patient, it may not be related to the PE. Thrombolysis: A randomized trial of weight-based IV tenecteplase vs placebo added to heparin compared outcomes in 500 patients in each group with intermediate PE, defined as requiring CT or echocardiographic RV dysfunction and elevated troponin. At day 30 tenecteplase deaths were 12 vs 16, respectively (p = 0.42) but significantly more strokes (12; 10 hemorrhagic, incidence 2.4%) vs 1 (incidence 0.2%) (p = 0.003), and extracranial bleeds occurred in 32 (6.3%) tenecteplase patients vs 6 (1.2%), (p < 0.001). Chronic thromboembolic pulmonary hypertension (CTEPH) was 2.6% in both groups after 3 years. An accompanying editorial concluded: No routine systemic thrombolysis; instead, observe for deterioration, for example, shock. To reduce bleeding, catheter-directed thrombolysis (CDT) for intermediate PE (mostly case series, sometimes ultrasound-enabled catheters; up to 20 mg rt-PA) has been reported. In the only randomized study (30 patients/group), ULTIMA, 90-day mortality (0 vs 1), RV/LV ratio, and TAPSE were the same as with anticoagulation. 24-hour pulmonary artery pressure results were superior with CDT. Recommendations: In intermediate PE, observe carefully. Bolus IV heparin 80 U/kg actual body weight during the diagnostic work-up, infuse 18 U/kg actual body weight if the PE diagnosis is proven or likely. Obtain baseline BNP or NT-proBNP and follow every 6–12 h to help assessment. If hypotension occurs, consider half- or full-dose rt-PA. If systemic thrombolysis is contraindicated, try catheter-directed thrombolysis by mechanical fragmentation or with 10–20 mg rt-PA infusion into the most important clot.
When active bleeding, impaired hemostasis, and high bleeding risk are concerns, give IV heparin without a bolus, 200–300 U/hour, and observe 6–8 h for hemostasis. Increase by 100 U every 8 h if tolerated without excessive bleeding until 600–800 U/h, then continue until bleeding risk remits. Consider a retrievable IVC filter.