1. Updates in the Management of High-Risk Pulmonary Embolism
Spotlight
Updates in the Management of High-Risk Pulmonary Embolism

2. Source and Credits
This presentation is based on the May 2019 AHRQ WebM&M Spotlight Case
See the full article at
CME credit is available
Commentary by: Emily L. Aaronson, MD, MPH, and Christopher Kabrhel, MD, MPH, Harvard Medical School
Editor, AHRQ WebM&M: Robert Wachter, MD
Spotlight Editor: Kiran Gupta, MD, MPH
Managing Editor: Erin Hartman, MS

3. Objectives
At the conclusion of this educational activity, participants should be able to:
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

4. Case: Management of High-Risk PE
A 45-year-old man with obesity presented to the ED with shortness of breath and hypoxia. The 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.

5. Case: Management of High-Risk PE (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.

6. Case: Management of High-Risk PE (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. The patient received a bed on the stepdown unit several hours later.

7. Case: Management of High-Risk PE (4)
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.

8. Background: Pulmonary Embolism
Common diagnosis
500,00–600,000 people diagnosed with PE each year in the United States
Cost associated with caring for patients with PE is high, a 2013 study suggests that each case costs approximately $8764
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; Available at
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
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:
Fanikos J, Rao A, Seger AC, Carter D, Piazza G, Goldhaber SZ. Hospital costs of acute pulmonary embolism. Am J Med. 2013;126:

9. Background: Pulmonary Embolism (2)
Numerous factors ("provoking factors") increase the risk of PE
Recent surgery, active cancer, pregnancy or being postpartum, estrogen exposure, prolonged limb immobility or bed rest, and the presence of indwelling catheters
Advanced age, cirrhosis, rheumatological disease, antiphospholipid antibody syndrome, smoking, obesity, and heart failure
Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353:

10. Pulmonary Embolism: Clinical Presentation
Classic presentation of PE
Shortness of breath, hypoxemia, tachycardia, evidence of right heart strain on ECG, and elevated BNP and troponin, as seen in this case
Dyspnea is the most common symptom of PE, followed by chest pain, cough, low grade fever, and syncope
Many patients present atypically and symptoms of PE are also typical of other common conditions, so correctly diagnosing PE can sometimes prove challenging
Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353:

11. Pulmonary Embolism: Risk Stratification
Certain presentations are associated with a higher risk of short-term mortality
Definition
Mortality
Massive PE
Hemodynamic instability: sustained hypotension (systolic blood pressure <90 mm Hg for greater than 15 minutes, or requiring inotropes)
Up to 65%
Submassive PE
Hemodynamically stable with 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%
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:

12. Pulmonary Embolism: Risk Stratification (2)
Patients diagnosed with PE should be risk-stratified based on presence of hemodynamic instability, right ventricular dysfunction, and myocardial necrosis
Risk stratification can help clinicians determine whether
Patient requires admission to a hospital floor or to intensive care unit
A pulmonary embolism response team should be activated
Advanced therapy such as thrombolysis or surgery is indicated
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:

13. Pulmonary Embolism: Management
Management is based on initial risk stratification
For low-risk PE and many intermediate-risk PEs, anticoagulation is the mainstay of treatment
Early anticoagulation reduces both PE mortality and recurrence rates
Although unfractionated heparin and warfarin traditionally have been most commonly used, treatment with direct-acting oral anticoagulants (DOACs) is increasingly common
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:

14. Pulmonary Embolism: Management (2)
For hemodynamically unstable patients (massive PE), treatment with systemic IV thrombolysis improves survival and is clinically indicated
For patients with likely submassive PE, the use of systemic thrombolysis is much more controversial
While systemic thrombolysis can reduce clinical deterioration in patients with submassive PE, it is associated with an unacceptable rate of major bleeding (intracranial hemorrhage)
Stein PD, Matta F. Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused. Am J Med. 2012;125:
Meyer G, Vicaut E, Danays T, et al; PEITHO Investigators. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370:

15. Catheter-Directed Therapy (CDT)
CDT offers the potential to reduce clot burden and right heart strain without increasing the risk of bleeding
CDT involves delivery of a relatively low dose of thrombolytic drug directly into pulmonary artery at the PE site
The procedure is typically performed by an interventional cardiologist, interventional radiologist, or vascular surgeon
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:
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:
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:

16. Catheter-Directed Therapy (2)
To date, only one, small, randomized clinical trial and several single-arm studies have evaluated CDT
Because the patient population most likely to benefit remains unknown, the decision to perform CDT is often challenging and is frequently clinician- and institution- dependent
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:
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:
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:

17. Pulmonary Embolism Response Teams
A multidisciplinary team of experts in management of VTE who, together
Rapidly assess patients with high-risk PE
Recommend the most appropriate treatment
Mobilize resources necessary for treatment
PERTs provide framework for multidisciplinary discussion of potential risks and benefits for an individual patient
May aid in decision to recommend catheter-directed thrombolysis
May reduce individual biases that any one provider or specialty might bring to a particular case
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 Sep 21: [Epub ahead of print].
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:

18. Pulmonary Embolism Response Teams (2)
Consensus-based team approach may relieve some concerns associated with recommending a high-risk therapy for a hemodynamically stable patient with submassive PE
PERT implementation is associated with
An increase in use of thrombolysis or thrombectomy (without an increase in bleeding)
A subjective sense among residents and fellows that the care of patients with high-risk PE is improved
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 Sep 21: [Epub ahead of print].
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:

19. Monitoring After CDT or Systemic Thrombolysis
Patients who undergo thrombolysis, whether systemic or CDT, should be admitted to an intensive care unit for close monitoring
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

20. Management After CDT
Though accepted that anticoagulation should be given post-thrombolysis, when and how to resume anticoagulation is not standardized
One survey found the most common approach was to continue heparin throughout thrombolysis with a subtherapeutic target (i.e., aPTT), but variation occurred in practice
A plan for post-thrombolysis anticoagulation including dose and timing of initiation should be clearly communicated during handoff of care from one team to the next
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:

21. This Case
The patient presented with signs and symptoms consistent with PE
Providers ordered a pulmonary embolism CT study
ECG and cardiac biomarkers (elevated troponin and BNP) suggested submassive PE
The patient was tachycardic but not hypotensive, so did not have a massive PE
The patient successfully underwent CDT, but no handoff regarding anticoagulation occurred
Recurrent thromboembolism due to inadequate anticoagulation was likely the cause of the patient's arrest

22. This Case: Tips for Improvement
Clinicians made many correct choices, but tools to support optimal care were lacking
Having a PERT in place to optimize coordination of care may have been helpful
Using standardized handoff tools for communication may have also helped
Using standardized postprocedure order sets may have facilitated correct ordering of anticoagulation for this patient after CDT
Once the patient arrested, having a team capable of rapidly mobilizing resources, such as extracorporeal membrane oxygenation (ECMO), might have been lifesaving
Starmer AJ, Spector ND, Srivastava R, et al; I-PASS Study Group. N Engl J Med. 2014;371:

23. Take-Home Points
Pulmonary embolism (PE) is a common diagnosis and can be fatal if appropriate treatment is not initiated rapidly
For submassive and massive PE, therapeutic options include anticoagulation, systemic intravenous 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

24. Take-Home Points (2)
Pulmonary embolism response teams (PERTs) can facilitate rapid patient assessment and risk stratification, multidisciplinary discussion of therapeutic options, and mobilization of resources for patients with massive and submassive PE
Because treatment plans are complex and individualized for each patient, clear communication among team members regarding therapeutic decisions is necessary to avoid medical errors