Cases & Commentaries
Updates in the Management of High-Risk Pulmonary Embolism
- Review common risk factors, typical presentation, methods for risk stratification, and the morbidity, mortality, and cost associated with pulmonary embolism.
- Describe the options for managing low-risk and high-risk pulmonary embolism, including recent developments in the treatment for submassive pulmonary embolism.
- Discuss the role of pulmonary embolism response teams in the management of higher risk pulmonary emboli.
Case and Commentary—Part 1
A 45-year-old man with obesity presented to the emergency department with shortness of breath and hypoxia. The evaluating physician ordered a CT scan of his chest, which revealed a large saddle pulmonary embolism (PE). The patient was tachycardic (heart rate 100 beats per minute), but not hypotensive. His oxygen saturation was 92% on room air. The patient's electrocardiogram (ECG) showed evidence of right heart strain, and laboratory results were notable for elevated brain natriuretic peptides (BNP) and troponin. Bedside ECG revealed right ventricular dysfunction.
Pulmonary embolism (PE) is a form of venous thromboembolism (VTE) where a clot dislodges from a deep vein and embeds in a pulmonary artery. Once in the pulmonary vasculature, the obstruction can increase pulmonary artery pressure and right ventricular afterload and can lead to right heart failure. Pulmonary embolism is common, with 500,000 to 600,000 people diagnosed each year in the United States. (1-3) The cost associated with caring for patients with PE is high; a 2013 study suggests that each case costs approximately $8764.(4)
Although nearly half of all PEs are idiopathic, numerous factors ("provoking factors") are known to increase the risk of PE. The factors most commonly implicated are a history of recent surgery, active cancer, pregnancy or being postpartum, estrogen exposure, prolonged limb immobility or bed rest, and the presence of indwelling catheters. Other conditions, such as advanced age, cirrhosis, rheumatological disease, antiphospholipid antibody syndrome, smoking, obesity, and heart failure also put patients at greater risk for developing PE.(5)
This patient's presentation, which included shortness of breath, hypoxemia, tachycardia, evidence of right heart strain on ECG, and elevated brain natriuretic peptides (BNP) and troponin, represents a classic presentation of PE. In addition to these signs, there are several other common signs and symptoms of PE. Dyspnea is the most common symptom, followed by chest pain, cough, low grade fever, and syncope.(5) Unfortunately, many patients present atypically and symptoms typical of PE are also typical of other common conditions, so correctly diagnosing PE can sometimes prove challenging.(5)
While PE can be fatal and is responsible for 180,000 deaths annually in the US alone (1,6), for most patients with PE, outcomes are quite favorable. Certain presentations are associated with a higher risk of short-term mortality. Patients who present with hemodynamic instability, often defined as sustained hypotension (5,7) Hemodynamically stable patients who have evidence of right ventricular dysfunction suggested by elevated BNP or ECG changes, or myocardial necrosis suggested by elevated troponin, (referred to as "submassive" or "intermediate-risk" PE) have a mortality rate of 5%–15%.(7) For patients without these features ("low-risk" PE), PE-related mortality is 1%–2%.(8) Thus, when the diagnosis of PE is made, patients should be risk stratified based on the presence of hemodynamic instability, right ventricular dysfunction, and myocardial necrosis (Table). Risk stratification can help clinicians determine whether the patient requires admission to a hospital floor or to an intensive care unit, whether a pulmonary embolism response team should be activated, and whether advanced therapy such as thrombolysis or surgery is indicated.
Case and Commentary—Part 2
The admitting ICU attending physician and the interventional radiologist discussed the case and decided to take the patient to the interventional radiology (IR) suite for catheter-guided thrombolysis. The procedure went well, and the patient was monitored in the ICU after the procedure. The following day, the catheters were removed in the IR suite.
The management of PE is based on initial risk stratification. For low-risk PE and many intermediate-risk PEs, anticoagulation remains the mainstay of treatment. Early anticoagulation reduces both PE mortality and recurrence rates.(9) Although unfractionated heparin and warfarin have historically been the anticoagulants most commonly used in the treatment of PE, treatment with direct-acting oral anticoagulants is increasingly common.
For high-risk PE, many experts recommend reducing clot burden through thrombolytic therapy or thrombectomy. For hemodynamically unstable patients (by definition, massive PE), treatment with systemic IV thrombolysis has been shown to improve survival and is clinically indicated.(10) However, for patients like this one (submassive PE), the use of systemic thrombolysis is much more controversial. Large studies have shown that while systemic thrombolysis can reduce clinical deterioration in patients with submassive PE, it is associated with an unacceptable rate of major bleeding, and in particular, intracranial hemorrhage.(11) The decision to use systemic thrombolytics is difficult and associated with risk, so it is not surprising that registry data show that treatment with systemic thrombolysis is rare (12)
Naturally, there is a great deal of interest in finding an approach that will reduce PE thrombus burden (and associated right heart dysfunction) without increasing the risk of bleeding. Catheter-directed thrombolysis (CDT) offers this potential. It involves delivery of a relatively low dose of thrombolytic drug (typically between 6 mg to 24 mg given over 12 to 24 hours—compared to 100 mg of systemic tissue plasminogen activator [tPA] given over 2 hours) directly into the pulmonary artery at the site of the PE. A CDT procedure is typically performed by an interventional cardiologist, interventional radiologist, or vascular surgeon. To date, only one small randomized clinical trial and several single-arm studies have evaluated CDT.(13-15) Because the patient population most likely to benefit remains unknown, the decision to perform CDT is often a challenging one to make and is frequently clinician- and institution-dependent.
Relatively new to PE management is the concept of the pulmonary embolism response team (PERT). Pulmonary embolism response teams may aid in the decision to recommend CDT by providing a framework for multidisciplinary discussion of the potential risks and benefits for an individual patient. A PERT is a multidisciplinary team of experts in the management of VTE who, together, rapidly assess patients with high-risk PE, recommend the most appropriate treatment, and mobilize resources necessary for treatment. Although PERTs are structured like other rapid response teams, unlike single-specialty approaches focused on expediting access to a particular treatment (e.g., percutaneous intervention for myocardial infarction), the PERT process invites discussion among a multidisciplinary team of medical, procedural, and surgical specialists. Such multidisciplinary discussion may reduce individual biases that any one physician or specialty might bring to a particular case.
From the clinician's perspective, the consensus-based team approach of PERT may relieve some of the anxiety associated with recommending a high-risk therapy for a hemodynamically stable patient with submassive PE. Recent studies show that implementation of a PERT is associated with an increase in the use of thrombolysis or thrombectomy (without an apparent increase in bleeding), and a subjective sense among residents and fellows that the care of patients with high-risk PE is improved.(16,17)
Case and Commentary—Part 3
The patient was sent from IR to the postanesthesia care unit for recovery, after which transfer to a telemetry bed on the stepdown unit was arranged. The ICU resident provided the accepting medicine team with signout but did not explicitly discuss the plan regarding anticoagulation.
Typically, patients who undergo thrombolysis, whether systemic or CDT, should be admitted to an intensive care unit for close monitoring. We also believe that patients with submassive and massive PE should be closely monitored even if thrombolysis is not planned, so that hemodynamic deterioration can be identified and managed immediately.
This case highlights another area of uncertainty—the restarting of anticoagulation after catheter-directed thrombolysis. While it is universally accepted that anticoagulation should be given post-thrombolysis, when and how to resume anticoagulation is not standardized. One survey of 113 PE specialists found that the most common approach was to continue heparin throughout thrombolysis with a subtherapeutic target (i.e., aPTT) for anticoagulation, though there was substantial variation in practice.(18) Regardless of the approach, a plan for post-thrombolysis anticoagulation including dose and timing of initiation should be clearly communicated when handing off care from one team to the next. In this case, the lack of communication regarding the need to restart heparin after CDT might have been avoided if the procedural specialists performing CDT, intensivists, and hematologists were on a single team that discussed the overall treatment plan.
Case and Commentary—Part 4
The patient received a bed on the stepdown unit several hours later. When the nurse went to check his vital signs, he noted the patient to be lethargic, tachycardic, and hypoxic, with oxygen saturations in the mid-80s on room air. The patient quickly lost his pulse and a code was called. He was intubated emergently and the code team discovered that the patient had never continued on a heparin drip after having the catheters removed. Although the code proceeded for about 40 minutes, there was no return of spontaneous circulation and the patient died.
This case represents a challenging one in which clinicians made many of the right choices, but the tools to support optimal care were not in place. The patient presented with signs and symptoms consistent with PE and providers ordered the appropriate diagnostic study, a pulmonary embolism CT study. An ECG was obtained, as were cardiac biomarkers, which suggested that the patient had a submassive PE (elevated troponin and BNP). He was tachycardic but not hypotensive, and so he did not clearly have a massive PE. At this point, it may have been helpful to have a PERT in place to optimize coordination of the patient's care. Pulmonary embolism response teams, in addition to advising on initial management, help manage patients throughout their hospital stay, intervene when needed, and coordinate long-term follow-up. In addition, having an institutional program such as a PERT in place often leads to the development of clear care pathways, including standardized postprocedure and admission order sets.
After the patient's successful catheter-directed thrombolysis procedure, the vignette notes that an explicit conversation about anticoagulation did not take place. Although we do not know for certain why this patient arrested, the most likely scenario is recurrent thromboembolism due to inadequate anticoagulation. Handoffs represent a vulnerable time for patients and inadequate communication can lead to medication errors, as in this case. The use of standardized handoff tools has been shown to decrease adverse events and improve safety.(19) Implementing such a tool may have helped the patient in this case. The use of standardized postprocedure order sets may also have facilitated correct ordering of anticoagulation for this patient after CDT. In addition, once the patient arrested, the presence of a team capable of rapidly mobilizing resources, such as extracorporeal membrane oxygenation (ECMO), might have been lifesaving.
- Pulmonary embolism is a common diagnosis and can be fatal if appropriate treatment is not initiated rapidly.
- For submassive and massive pulmonary embolism, there are many therapeutic options including anticoagulation, systemic IV thrombolysis, catheter-directed thrombolysis, surgical embolectomy, and catheter-directed embolectomy.
- Robust clinical trial data are not available comparing these therapies; clinicians must choose based on expert opinion.
- Pulmonary embolism response teams can facilitate rapid patient assessment and risk stratification, multidisciplinary discussion of therapeutic options, and mobilization of resources for patients with massive and submassive pulmonary embolism.
- Because treatment plans are complex and individualized for each patient, clear communication among team members regarding therapeutic decisions is necessary to avoid medical errors.
Emily L. Aaronson, MD, MPH
Department of Emergency Medicine, Massachusetts General Hospital
Assistant Chief Quality Officer, Edward P. Lawrence Center for Quality and Safety
Assistant Professor of Emergency Medicine, Harvard Medical School
Christopher Kabrhel, MD, MPH
Director, Center for Vascular Emergencies, Department of Emergency Medicine, Massachusetts General Hospital
Associate Professor of Emergency Medicine, Harvard Medical School
Faculty Disclosures: Dr. Aaronson has declared that neither she, nor any immediate member of her family, has a financial arrangement or other relationship with the manufacturers of any commercial products discussed in this continuing medical education activity. Dr. Kabrhel has received grant funding for VTE research from Janssen, Diagnostica Stago, and Siemens; he also serves on the Advisory Board for Salix. The commentary does not include information regarding investigational or off-label use of products or devices. All conflicts of interest have been resolved in accordance with the ACCME Updated Standards for commercial support.
Table. Clinical Definitions of Pulmonary Embolism.(20)
|Massive PE||Sustained hypotension (systolic blood pressure||Up to 65%|
|Submassive PE||Right ventricular dysfunction (elevated BNP or ECG changes) or myocardial necrosis (elevated troponin) without hypotension||5%–15%|
|Low-Risk PE||Normotensive and no markers of adverse prognosis||1%–2%|
1. The Surgeon General's Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Rockville, MD: US Office of the Surgeon General, US National Heart, Lung, and Blood Institute; 2008. [go to PubMed]
2. Heit JA, Cohen AT, Anderson FA II. Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. Blood. 2005;106:910. [Available at]
3. Anderson FA II, Zayaruzny M, Heit JA, Fidan D, Cohen AT. Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism. Am J Hematol 2007; 82:777-782. [go to PubMed]
4. Fanikos J, Rao A, Seger AC, Carter D, Piazza G, Goldhaber SZ. Hospital costs of acute pulmonary embolism. Am J Med. 2013;126:127-132. [go to PubMed]
5. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353:1386-1389. [go to PubMed]
6. Beckman MG, Hooper WC, Critchley SE, Ortel TL. Am J Prev Med. 2010;38(suppl 4):S495-S501. [go to PubMed]
7. Secemsky E, Chang Y, Jain CC, et al. Contemporary management and outcomes of patients with massive and submassive pulmonary embolism. Am J Med. 2018;131:1506-1514. [go to PubMed]
8. Elias A, Mallett S, Daoud-Elias M, Poggi JN, Clarke M. Prognostic models in acute pulmonary embolism: a systematic review and meta-analysis. BMJ Open. 2016;6:e010324. [go to PubMed]
9. Smith SB, Geske JB, Maguire JM, Zane NA, Carter RE, Morgenthaler TI. Early anticoagulation is associated with reduced mortality for acute pulmonary embolism. Chest. 2010;137:1382-1390. [go to PubMed]
10. Stein PD, Matta F. Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused. Am J Med. 2012;125:465-470. [go to PubMed]
11. Meyer G, Vicaut E, Danays T, et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370:1402-1411. [go to PubMed]
12. Pollack CV, Schreiber D, Goldhaber SZ, 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;57:700-706. [go to PubMed]
13. Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation. 2013;129:479-486. [go to PubMed]
14. Kuo WT, Banerjee A, Kim PS, et al. Pulmonary Embolism Response to Fragmentation, Embolectomy, and Catheter Thrombolysis (PERFECT): initial results from a prospective multicenter registry. Chest. 2015;148:667-673. [go to PubMed]
15. Piazza G, Hohlfelder B, Jaff MR, et al; SEATTLE II Investigators. A prospective, single-arm, multicenter trial of ultrasound-facilitated, catheter-directed, low-dose fibrinolysis for acute massive and submassive pulmonary embolism: the SEATTLE II Study. JACC Cardiovasc Interv. 2015;8:1382-1392. [go to PubMed]
16. Rosovsky R, Chang Y, Rosenfield K, et al. Changes in treatment and outcomes after creation of a pulmonary embolism response team (PERT), a 10-year analysis. J Thromb Thrombolysis. 2019;47:31-40. [go to PubMed]
17. Elbadawi A, Wright C, Patel D, et al. The impact of a multi-specialty team for high risk pulmonary embolism on resident and fellow education. Vasc Med. 2018;23:372-376. [go to PubMed]
18. Todoran TM, Giri J, Barnes GD, et al; PERT Consortium. Treatment of submassive and massive pulmonary embolism: a clinical practice survey from the second annual meeting of the Pulmonary Embolism Response Team Consortium. J Thromb Thrombolysis. 2018;46:39-49. [go to PubMed]
19. Starmer A, Spector N, Srivastava R, et al. Changes in medical errors after implementation of a handoff program. N Engl J Med. 2014;371:1803-1812. [go to PubMed]
20. Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123:1788-1830. [go to PubMed]