Pulmonary embolism treatment approach
|
Pulmonary Embolism Microchapters |
|
Diagnosis |
|---|
|
Pulmonary Embolism Assessment of Probability of Subsequent VTE and Risk Scores |
|
Treatment |
|
Follow-Up |
|
Special Scenario |
|
Trials |
|
Case Studies |
|
Pulmonary embolism treatment approach On the Web |
|
Directions to Hospitals Treating Pulmonary embolism treatment approach |
|
Risk calculators and risk factors for Pulmonary embolism treatment approach |
Editor(s)-In-Chief: C. Michael Gibson, M.S., M.D. [1], The APEX Trial Investigators; Associate Editor(s)-In-Chief: Kashish Goel, M.D.; Rim Halaby, M.D. [2]
Overview
Prompt recognition, diagnosis and treatment of pulmonary embolism is critical. Anticoagulant therapy is the mainstay of treatment for patients who are hemodynamically stable. If hemodynamic compromise is present, then fibrinolytic therapy is recommended.
Step 1: Confirm PE
Shown below is an algorithm depicting the initial diagnostic approach to pulmonary embolism.[1][2]
| Does the patient who is suspected to have PE have hypotension or shock? | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Yes | No | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Suspected high-risk PE | Suspected non-high risk PE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Administer anticoagulation (in case there are no contraindications) during the diagnostic workup | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Is a CT available immediately? | What is the pretest probability of PE? Assess the pretest probability of PE by using one of the risk score: - Wells score - Geneva score - PERC | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No | Yes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Order echocardiography | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Does the patient have RV overload? | Low pretest probability | Intermediate pretest probability | High pretest probability OR PE is likely | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Administer anticoagulation (in case there are no contraindications) during the diagnostic workup | Administer anticoagulation (in case there are no contraindications) during the diagnostic workup | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No | Yes | Order CT | Order D-dimer | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Positive | Negative | Positive | Negative | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Is the patient unstable OR no other tests are available? | Is the patient stabilized AND CT is now available? | Order CT | PE is excluded | Order CT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Positive | Negative | Positive | Negative | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PE is excluded | Consider thrombolytic therapy or embolectomy | Order CT | PE is confirmed | PE is excluded | PE is confirmed | PE is excluded | PE is confirmed | PE is excluded | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Positive for PE | Negative for PE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PE is confirmed | PE is excluded | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Step 2: Initial Treatment
Shown below is an algorithm depicting the initial management of pulmonary embolism.[1][2]
| Assess the severity of pulmonary embolism | |||||||||||||||||||||||||||||||||||||||||||||||||
| Massive PE (also known as high-risk PE) Cardiogenic shock OR Persistent hypotension (≤90mmHg) OR Drop of the blood pressure by ≥ 40mmHg for > 15 min[3] OR Pulselessness OR Profound bradycardia (<40 bpm) with findings of shock[4] | Submassive PE (also know as intermediate-risk PE) Right ventricular dysfunction AND/OR Myocardial injury (Troponin +) | Low-risk PE No cardiogenic shock AND No hypotension AND No right ventricular dysfunction AND No myocardial injury (Troponin -) | |||||||||||||||||||||||||||||||||||||||||||||||
| Provide hemodynamic and respiratory support Begin high dose unfractionated heparin [3]: Bolus 10.000 U
Administer rapidly 500-1000 mL of normal saline (Caution with fluid overload)[3] | |||||||||||||||||||||||||||||||||||||||||||||||||
| Is there any contraindication for fibrinolytic therapy? | Is there any contraindication for anticoagulation therapy? | Is there any contraindication for anticoagulation therapy? | |||||||||||||||||||||||||||||||||||||||||||||||
| NO | YES | NO | YES | NO | YES | ||||||||||||||||||||||||||||||||||||||||||||
| Discontinue unfractionated heparin AND Begin fibrinolytic therapy | Surgical pulmonary embolectomy OR Percutaneous catheter embolectomy | Anticoagulation therapy AND Hospital admission | IVC filter AND Hospital admission | Anticoagulation therapy AND Early discharge/home treatment | IVC filter AND Early discharge/home treatment | ||||||||||||||||||||||||||||||||||||||||||||
| Does the patient fail to improve OR Develop cardiogenic shock? OR Develop hypotension? | Does the patient fail to improve OR Develop cardiogenic shock? OR Develop hypotension (<90 mmHg)? OR Develop respiratory distress (SaO2<95% with Borg score>8 or altered mental status) OR Have moderate to severe RV dysfunction (RV hypokinesis or estimated RVSP>40 mmHg) OR Elevated biomarkers (troponin> upper limit of normal, BNP>100 pg/mL, or pro-BNP>900 pg/mL)[4] | ||||||||||||||||||||||||||||||||||||||||||||||||
| YES | NO | YES | NO | ||||||||||||||||||||||||||||||||||||||||||||||
| Surgical pulmonary embolectomy OR Percutaneous catheter embolectomy | Continue with the same treatment | Is there any contraindication for fibrinolytic therapy? | Continue with the same treatment | ||||||||||||||||||||||||||||||||||||||||||||||
| NO | YES | ||||||||||||||||||||||||||||||||||||||||||||||||
| Hold anticoagulation and give thrombolytics | Surgical pulmonary embolectomy OR Percutaneous catheter embolectomy | ||||||||||||||||||||||||||||||||||||||||||||||||
| Does the patient fail to improve? | |||||||||||||||||||||||||||||||||||||||||||||||||
| YES | NO | ||||||||||||||||||||||||||||||||||||||||||||||||
| Surgical pulmonary embolectomy OR Percutaneous catheter embolectomy | Continue with the same treatment | ||||||||||||||||||||||||||||||||||||||||||||||||
Anticoagulation
The most common cause of mortality in patients with a pulmonary embolism, is a recurrent PE occurring within a few hours of the initial event.[5] Anticoagulation prevents further clot formation and extension, therefore it should be started as early as possible. Anticoagulation does not disaggregate existing clot, but it does facilitate the action of the body's endogenous lytic system. Anticoagulation is the cornerstone of therapy in an acute pulmonary embolism.[5][6] After initial risk stratification. Certain conditions like pericardial tamponade and aortic dissection can mimic pulmonary embolism. The use of anticoagulants is contraindicated in these medical conditions. Proceed with caution if these conditions are high on the differential. Immediate treatment should be initiated based on the following guidelines: [2][4][1]
- Initial treatment with parenteral anticoagulants, including subcutaneous low molecular weight heparin (such as enoxaparin and dalteparin), subcutaneous fondaparinux, or intravenous unfractionated heparin, should be administered unless contraindicated.
- ACCP guidelines[2] recommend low molecular weight heparin or fondaparinux instead of intravenous unfractionated heparin.
- If there is moderate-to-high clinical suspicion of a PE, anticoagulation should be initiated while awaiting confirmatory tests.
- Vitamin K antagonists such as warfarin should be started the same day. Parenteral anticoagulation should be continued for at least 5 days, and preferably until INR is 2.0 or above for 1-2 days.
- Warfarin therapy often requires frequent dose adjustment and monitoring of the INR. In PE, the INR goal should be between 2.0 and 3.0.
- In patients with suspected or confirmed heparin-induced thrombocytopenia, lepirudin or argatroban should be used.
Thrombolysis
- Unless previously contraindicated, thrombolysis is indicated in patients with a massive PE or those with a submassive PE who develop or are at risk of developing hypotension (SBP < 90 mmHg).
- Administration of a fibrinolytic via a peripheral intravenous catheter is recommended.
- FDA recommends a 100 mg dose of alteplase administered as a continuous infusion over 2 hours. This treatment is supported by AHA[4] and ACCP guidelines.[2]
- Withhold anticoagulation during the 2 hours of fibrinolytic infusion.
- The role of thrombolysis in a submassive PE is not established at this point.[7] Two ongoing trials are investigating the efficacy and safety of this approach.
- No large clinical trial has demonstrated a mortality benefit of thrombolytic therapy. However, it helps by accelerating clot lysis, improving pulmonary perfusion, and improving right ventricular function.[8][9]
To read more about dosage, contraindications, and guidelines, click here.
Surgical Procedures
- Catheter-assisted thrombus removal is recommended in patients with a massive PE who have contraindications to thrombolytic therapy or have failed thrombolysis.
- Thrombectomy is also recommended for patients who are in severe shock that may cause the patient to die before thrombolysis takes effect (hours).
- Pulmonary embolectomy is also recommended if a patient with the above conditions fails catheter-assisted embolectomy.
IVC Filter
- An IVC filter is indicated for patients for whom anticoagulation is contraindicated.
- Anticoagulation should be restarted once the contraindication is resolved.
Step 3: Long Term Treatment
- After treatment in the hospital, the patient should continue anticoagulation treatment for 3 months if the PE is provoked by surgery or a nonsurgical transient risk factor.
- An abnormal D-dimer level at the end of the treatment course might signal the need for continued treatment with anticoagulation for a first time unprovoked pulmonary embolus.[10]
- Long-term treatment is usually recommended with vitamin K antagonists like warfarin, unless contraindicated or some special circumstances.
- The recommended therapeutic INR range for patients with PE is 2.0-3.0.
- Continued warfarin administration needs close monitoring. The patient should have an appointment with the "anticoagulation clinic" before leaving the hospital.
Extended Anticoagulation
Extended Treatment means extending the anticoagulation therapy beyond the first 3 months. It is recommended in the following scenarios:
- For a pulmonary embolism that is unprovoked. The patient's risk should be re-evaluated at 3 months to consider whether or not extended therapy is warranted.
- Active cancer.
- Recurrent venous thromboembolism.
- Chronic thrombembolic pulmonary hypertension.
Salient Features:
- For extended therapy, the continued need for anticoagulation and the risk-benefit ratio should be re-evaluated at periodic intervals (eg, annually).
- Patients with recurrent thromboembolic disease, with or without anticoagulation, should be evaluated for possible thrombophilias.
Specific Circumstances
- Malignancy: Low molecular weight heparin is favored over warfarin based on the results of the CLOT trial.[11]
- Pregnancy: Low molecular weight heparin is preferred to avoid the known teratogenic effects of warfarin.
- Asymptomatic patients who are diagnosed with an incidental PE should be managed with the same criteria as those with symptomatic PE.
Newer Anticoagulants
- Dabigatran (direct thrombin inhibitor), Rivaroxaban (Factor Xa inhibitor), and other drugs in the same classes, provide an alternate option to warfarin/LMWH for treatment of PE.
- Advantages include the availability of an oral formulation, no frequent monitoring requirement, a predictable effect profile, and few (known) drug interactions.
- Disadvantages include the currently limited prospective trial data, the theoretical interaction with statins (as they are metabolized by the same CYP3A4 enzyme), and the risk of bleeding.
References
- ↑ 1.0 1.1 1.2 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.
- ↑ 2.0 2.1 2.2 2.3 2.4 Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ; et al. (2012). "Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e419S–94S. doi:10.1378/chest.11-2301. PMC 3278049. PMID 22315268.
- ↑ 3.0 3.1 3.2 3.3 3.4 Kucher N, Goldhaber SZ (2005). "Management of massive pulmonary embolism". Circulation. 112 (2): e28–32. doi:10.1161/CIRCULATIONAHA.105.551374. PMID 16009801.
- ↑ 4.0 4.1 4.2 4.3 Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ; et al. (2011). "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. 123 (16): 1788–830. doi:10.1161/CIR.0b013e318214914f. PMID 21422387.
- ↑ 5.0 5.1 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) - ↑ 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) - ↑ Dong B, Jirong Y, Liu G, Wang Q, Wu T. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev 2006;(2):CD004437. PMID 16625603.
- ↑ 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) - ↑ 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) - ↑ Palareti G, Cosmi B, Legnani C; et al. (2006). "D-dimer testing to determine the duration of anticoagulation therapy". N. Engl. J. Med. 355 (17): 1780–9. doi:10.1056/NEJMoa054444. PMID 17065639.
- ↑ Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M (2003). "Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer". N Engl J Med. 349 (2): 146–53. PMID 12853587.