Pulmonary embolism treatment approach

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Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

Pulmonary embolism (PE) is a potentially lethal condition, with a mortality rate close to 30 percent without treatment. Thus, prompt therapy is of utmost important. In most cases, anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such as oxygen or analgesia, are often required.

Triage

One of the most important aspects in the care of a patient with acute PE is triage or early risk stratification.

  • Patients who are diagnosed with a low-risk PE may require only anticoagulation and medical ward admission.
  • On the other hand, patients with massive PE or those with submassive PE who do not improve clinically may benefit from thrombolysis and ICU admission. Initial supportive therapies in these patients may include:
    • Respiratory support with oxygen for hypoxemic patients or mechanical ventilation in cases of severe hypoxemia or respiratory failure.
    • Hemodynamic support with intravenous fluids or intravenous vasopressors for hypotensive patients. Intravenous fluids should be administered cautiously, as increased right ventricular load can disable the right ventricular oxygen supply-to-demand balance.[1]

Anticoagulation

Initial anticoagulation

Long-term anticoagulation

Extended anticoagulation

Specific circumstances

Newer anticoagulants

Thrombolysis

Thrombolysis can be used in cases of severe PE, when surgery is not immediately available or possible (e.g. peri-arrest or during cardiac arrest). The only trial that addressed this issue had 8 patients; the four receiving thrombolysis survived, while the four who received only heparin died.[2]

The use of thrombolysis in moderate PE is still debatable. The aim of the therapy is to dissolve the clot, but there is an attendant risk of bleeding or stroke.[3]

No large clinical trial has demonstrated mortality benefit of thrombolytic therapy. However, it helps in the following ways[4]

  1. It accelerates clot-lysis, thereby relieving acute PE.
  2. It improves Right Ventricular function.
  3. It improves pulmonary perfusion and cardiovascular function.[5]

Major risk factor associated with thrombolytic therapy are:

To read more about dosage, contraindications and guidelines, click here.

Treatment algorithm

Compression Stockings

Depending on the clinical presentation, initial therapy is primarily aimed at:

  1. Restoration of flow through occluded pulmonary arteries, OR
  2. Prevention of potentially fatal early recurrences.

Most common reason for mortality is recurrent PE, occurring within the few hours of the initial event[6]. Anticoagulant therapy decreases mortality by 2% to 8%, thus making it absolutely necessary to start therapy as soon as possible[7].

Majority of the patients should be started on anticoagulation, with one of the following drugs[8][9]:

Treatment Protocol[10]

 
 
 
 
 
 
 
Stabilize the patient
  • Respiratory Support
  • Hemodynamic Support
  • Anticoagulation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initial Treatment options (≤5 Days)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Long term treatment (≥3 Month) (INR target, 2.0-3.0)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Extended treatment (Indefinite) (INR target, 2.0-3.0 OR 1.5-1.9)

Extended treatment should be considered in patients with:

  1. Active Cancer.
  2. Unprovoked Pulmonary embolism.
  3. Recurrent venous thromboembolism.

Indefinite treatment refers to continued anticoagulation without a pre-scheduled stop date.

Anticoaulation may be stopped because of:

  1. Risk of bleeding.
  2. Change in patients preference.

Treatment of choice:Special considerations

Treatment Algorithm

 
 
 
 
 
 
 
Stabilize the patient
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is anticoagulation contraindicated ?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diagnostic evaluation
 
 
 
 
 
 
 
Anticoagulate with SC LMWH or IV UFH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PE excluded
 
PE confirmed
 
 
 
 
 
Diagnostic evaluation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No further Treatment
 
Inferior vena cava filter
 
 
PE excluded
 
PE confirmed
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discontinue Anticoagulants
 
Clinicaly severe enough to need Thrombolysis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is thrombolytic Contraindicated?
 
Continue Anticoagulants
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical emblectomy or catheter based interventions
 
Hold Anticoagulation, Give Thrombolytics then resume Anticoagulations
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient shows clinical improvement
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Surgical emblectomy or catheter based interventions
 
Continue anticoagulation

References

  1. Mercat A, Diehl JL, Meyer G, Teboul JL, Sors H (1999). "Hemodynamic effects of fluid loading in acute massive pulmonary embolism". Crit. Care Med. 27 (3): 540–4. PMID 10199533. Retrieved 2011-12-12. Unknown parameter |month= ignored (help)
  2. Jerjes-Sanchez C, Ramirez-Rivera A, de Lourdes Garcia M, Arriaga-Nava R, Valencia S, Rosado-Buzzo A, Pierzo JA, Rosas E. Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism: A Randomized Controlled Trial. J Thromb Thrombolysis 1995;2:227-229. PMID 10608028.
  3. Dong B, Jirong Y, Liu G, Wang Q, Wu T. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev 2006;(2):CD004437. PMID 16625603.
  4. Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W (2002). "Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism". N. Engl. J. Med. 347 (15): 1143–50. doi:10.1056/NEJMoa021274. PMID 12374874. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  5. Levine M, Hirsh J, Weitz J, Cruickshank M, Neemeh J, Turpie AG, Gent M (1990). "A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism". Chest. 98 (6): 1473–9. PMID 2123152. Retrieved 2011-12-21. Unknown parameter |month= ignored (help)
  6. Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI, Schwartz JS, Thompson BT, Popovich J, Hobbins TE (1992). "The clinical course of pulmonary embolism". N. Engl. J. Med. 326 (19): 1240–5. doi:10.1056/NEJM199205073261902. PMID 1560799. Retrieved 2011-12-12. Unknown parameter |month= ignored (help)
  7. Goldhaber SZ, Visani L, De Rosa M (1999). "Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER)". Lancet. 353 (9162): 1386–9. PMID 10227218. Retrieved 2011-12-12. Unknown parameter |month= ignored (help)
  8. Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ; et al. (2008). "Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)". Chest. 133 (6 Suppl): 454S–545S. doi:10.1378/chest.08-0658. PMID 18574272.
  9. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P; et al. (2008). "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. 29 (18): 2276–315. doi:10.1093/eurheartj/ehn310. PMID 18757870.
  10. Agnelli G, Becattini C (2010). "Acute pulmonary embolism". N Engl J Med. 363 (3): 266–74. doi:10.1056/NEJMra0907731. PMID 20592294.

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