Pulmonary embolism treatment approach: Difference between revisions
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==Initial treatment== | ==Initial treatment== | ||
===Anticoagulation=== | ===Anticoagulation=== | ||
The most common of mortality in patients with a pulmonary embolism, is a recurrent [[PE]] occurring within a few hours of the initial event<ref name="pmid1560799">{{cite journal |author=Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI, Schwartz JS, Thompson BT, Popovich J, Hobbins TE |title=The clinical course of pulmonary embolism|journal=N. Engl. J. Med. |volume=326 |issue=19 |pages=1240–5 |year=1992 |month=May |pmid=1560799|doi=10.1056/NEJM199205073261902|url=http://dx.doi.org/10.1056/NEJM199205073261902 |accessdate=2011-12-12}}</ref>. Anticoagulation is the cornerstone of therapy in acute [[pulmonary embolism]]<ref name="pmid1560799">{{cite journal |author=Carson JL, Kelley MA, Duff A, Weg JG, Fulkerson WJ, Palevsky HI, Schwartz JS, Thompson BT, Popovich J, Hobbins TE |title=The clinical course of pulmonary embolism|journal=N. Engl. J. Med. |volume=326 |issue=19 |pages=1240–5 |year=1992 |month=May |pmid=1560799|doi=10.1056/NEJM199205073261902|url=http://dx.doi.org/10.1056/NEJM199205073261902 |accessdate=2011-12-12}}</ref><ref name="pmid10227218">{{cite journal |author=Goldhaber SZ, Visani L, De Rosa M|title=Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER) |journal=Lancet |volume=353|issue=9162|pages=1386–9 |year=1999 |month=April |pmid=10227218 |doi=|url=http://linkinghub.elsevier.com/retrieve/pii/S0140673698075345|accessdate=2011-12-12}}</ref>. After initial risk stratification, immediate treatment should be initiated based on the following guidelines. <ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref><ref name="pmid21422387">{{cite journal |author=Jaff MR, McMurtry MS, Archer SL, ''et al.'' |title=Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association |journal=Circulation |volume=123 |issue=16 |pages=1788–830 |year=2011 |month=April |pmid=21422387 |doi=10.1161/CIR.0b013e318214914f |url=}}</ref><ref name="pmid18757870">{{cite journal |author=Torbicki A, Perrier A, Konstantinides S, ''et al.'' |title=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) |journal=Eur. Heart J. |volume=29 |issue=18 |pages=2276–315 |year=2008 |month=September |pmid=18757870 |doi=10.1093/eurheartj/ehn310 |url=}}</ref>: | |||
* Initial treatment with parenteral anticoagulants including subcutaneous [[low molecular weight heparin|Low molecular weight heparin]](such as [[enoxaparin]] and [[dalteparin]]), subcutaneous [[Fondaparinux]] or intravenous [[unfractionated heparin]], unless contraindicated. | * Initial treatment with parenteral anticoagulants including subcutaneous [[low molecular weight heparin|Low molecular weight heparin]](such as [[enoxaparin]] and [[dalteparin]]), subcutaneous [[Fondaparinux]] or intravenous [[unfractionated heparin]], unless contraindicated. | ||
* [[ACCP guidelines]]<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommend [[low molecular weight heparin]] or [[fondaparinux]] over intravenous [[unfractionated heparin]]. | * [[ACCP guidelines]]<ref name="pmid22315268">{{cite journal |author=Kearon C, Akl EA, Comerota AJ, ''et al.'' |title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines |journal=Chest |volume=141 |issue=2 Suppl |pages=e419S–94S |year=2012 |month=February |pmid=22315268 |doi=10.1378/chest.11-2301 |url=}}</ref> recommend [[low molecular weight heparin]] or [[fondaparinux]] over intravenous [[unfractionated heparin]]. | ||
* | * If there is moderate-to-high clinical suspicion of PE, anticoagulation should be initiated while awaiting confirmatory tests. | ||
* [[Vitamin K antagonists]] | * [[Vitamin K antagonists]] such as [[warfarin]] should be started the same day and parenteral anticoagulation should be continued for at least 5 days, and preferably until INR is 2.0 or above for 1-2 days. | ||
* In patients with suspected or confirmed [[heparin-induced thrombocytopenia]], [[lepirudin]] or [[argatroban]] should be used. | * In patients with suspected or confirmed [[heparin-induced thrombocytopenia]], [[lepirudin]] or [[argatroban]] should be used. | ||
Revision as of 15:36, 11 May 2012
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Pulmonary Embolism Microchapters |
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Diagnosis |
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Pulmonary Embolism Assessment of Probability of Subsequent VTE and Risk Scores |
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Treatment |
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Follow-Up |
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Special Scenario |
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Trials |
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Case Studies |
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Pulmonary embolism treatment approach On the Web |
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Directions to Hospitals Treating Pulmonary embolism treatment approach |
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Risk calculators and risk factors for Pulmonary embolism treatment approach |
Editor(s)-In-Chief: The APEX Trial Investigators, C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Kashish Goel, M.D.; Ujjwal Rastogi, MBBS [2]; Cafer Zorkun, M.D., Ph.D. [3]
Overview
Pulmonary embolism (PE) is a potentially lethal condition, and without treatment has a mortality rate of 30%, thus prompt treatment is of utmost importance. In most cases, anticoagulant therapy is the mainstay of treatment. A proposed treatment algorithm is presented at the end of this chapter, and all of the contemporary guidelines for the treatment of an acute PE are listed here.
Risk stratification
Triage and early risk stratification are two of the most important aspects in the care of a patient with acute PE.
- Low-risk PE: Therapeutic anticoagulation, unless contraindicated.
- Submassive PE: If the patient is hemodynamically stable without major RV dysfunction or infarction, therapeutic anticoagulation should be started. In some cases, thrombolysis may be indicated.
- Massive PE: Thrombolysis is indicated and ICU admission may be required. Initial supportive therapies for these patients may include:
- Respiratory support with oxygen for hypoxemic patients and mechanical ventilation in cases of severe hypoxemia or pending respiratory failure.
- Hemodynamic support with intravenous fluids or intravenous vasopressors for hypotensive patients. Intravenous fluids should be administered with caution as increased right ventricular load can disable the oxygen balance.[1]
- If anticoagulation is contraindicated, an IVC filter is recommended.
Initial treatment
Anticoagulation
The most common of mortality in patients with a pulmonary embolism, is a recurrent PE occurring within a few hours of the initial event[2]. Anticoagulation is the cornerstone of therapy in acute pulmonary embolism[2][3]. After initial risk stratification, immediate treatment should be initiated based on the following guidelines. [4][5][6]:
- Initial treatment with parenteral anticoagulants including subcutaneous Low molecular weight heparin(such as enoxaparin and dalteparin), subcutaneous Fondaparinux or intravenous unfractionated heparin, unless contraindicated.
- ACCP guidelines[4] recommend low molecular weight heparin or fondaparinux over intravenous unfractionated heparin.
- If there is moderate-to-high clinical suspicion of PE, anticoagulation should be initiated while awaiting confirmatory tests.
- Vitamin K antagonists such as warfarin should be started the same day and parenteral anticoagulation should be continued for at least 5 days, and preferably until INR is 2.0 or above for 1-2 days.
- In patients with suspected or confirmed heparin-induced thrombocytopenia, lepirudin or argatroban should be used.
Other salient features:
- Prevents further clot formation, so should be started as early as possible.
- It has no effect on pre-existing clot lysis.
- It has no effect in decreasing the size of thrombus.
- Warfarin therapy often requires frequent dose adjustment and monitoring of the INR. In PE, INRs between 2.0 and 3.0 are generally considered ideal.
- Anticoagulation should be used with caution, because certain conditions like pericardial tamponade and aortic dissection can mimic pulmonary embolism, but the use of anticoagulants is contraindicated in these medical conditions.
Thrombolysis
- 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), unless contraindicated.
- Administration of a fibrinolytic is recommended via a peripheral intravenous catheter.
- FDA recommends infusion dose of alteplase 100 mg as a continuous infusion over 2 hours, supported by AHA[5] and ACCP guidelines[4].
- Withhold anticoagulation during these 2 hours of fibrinolytic infusion.
- The role of thrombolysis in submassive PE in not established at this point[7]. Two ongoing trials are investigating this.
- No large clinical trial has demonstrated mortality benefit of thrombolytic therapy. However, it helps by accelerating clot lysis, improving pulmonary perfusion and 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 massive PE, who have contraindications or failed thrombolysis, or are in shock that will cause death before thrombolysis takes effect (hours).
- Pulmonary embolectomy is recommended if a patient with above conditions fails catheter-assisted embolectomy.
IVC filter
- IVC filter is indicated in whom anticoagulation is contraindicated.
- Anticoagulation should be restarted, once the contraindication is resolved.
Long-term treatment
- After initial treatment in the hospital, patient should continue anticoagulation for 3 months for a PE provoked by surgery or nonsurgical transient risk factor.
- An abnormal D-dimer level at the end of treatment might signal the need for continued treatment among patients with a first unprovoked pulmonary embolus.[10]
- Long-term treatment is usually recommended with vitamin K antagonists like warfarin, unless contraindicated or some special circumstances.
- Recommended therapeutic INR range for patients with PE is 2.0-3.0.
- Warfarin administration needs close monitoring as an outpatient and patient should have an appointment with "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 situations:
- For an unprovoked PE, patient's risk should be re-evaluated at 3 months to be considered for extended therapy.
- Active Cancer.
- Recurrent venous thromboembolism.
- Chronic thrombembolic pulmonary hypertension.
Salient features:
- For extended therapy, the 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.
- Assymptomatic 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 same classes provide an alternate option to warfarin/LMWH for treatment of PE.
- Advantages include oral formulation, does not require frequent monitoring, have a predictable effect and few (known) drug interactions.
- Disadvantages include the currently limited prospective experience, theoretical interaction with statins as they are metabolized at least in part by the same cytochrome enzyme, CYP3A4 and risk of bleeding.
- Current recommendations still favor warfarin or low molecular weight heparin over the new anticoagulants[4] because of the paucity of available data. It is possible that these recommendations will change with the availability of more data in this specific patient population.
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
- ↑ 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) - ↑ 2.0 2.1 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) - ↑ 4.0 4.1 4.2 4.3 Kearon C, Akl EA, Comerota AJ; 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. PMID 22315268. Unknown parameter
|month=ignored (help) - ↑ 5.0 5.1 Jaff MR, McMurtry MS, Archer SL; 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. Unknown parameter
|month=ignored (help) - ↑ Torbicki A, Perrier A, Konstantinides S; 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. 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.