RESPIRATORY THERAPY GUIDE

Pulmonary embolism (PE)

Pulmonary embolism (PE) is a blockage of the pulmonary artery (or one of its branches), usually when a venous thrombus (blood clot from a vein), becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs. This process is termed thromboembolism.

Symptoms may include difficulty breathing, pain in the chest during breathing, and in more severe cases collapse, circulatory instability and sudden death. Treatment, usually, is with anticoagulant medication, such as heparin and warfarin, and rarely (in severe cases) with thrombolysis or surgery. In other, rarer forms of pulmonary embolism, material other than a blood clot is responsible; this may include fat or bone (usually in association with significant trauma), air (often when diving), clumped tumor cells, and amniotic fluid (affecting mothers during childbirth).

Treatment

In most cases, anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such as oxygen or analgesia, are often required.
Massive PE causing hemodynamic instability (marked decreased oxygen saturation, tachycardia and/or hypotension) is an indication for thrombolysis, the enzymatic destruction of the clot with medication. Some advocate its use also if right ventricular dysfunction can be demonstrated on echocardiography.[18]

Anticoagulation

In most cases, anticoagulant therapy is the mainstay of treatment. Heparin, low molecular weight heparins (such as enoxaparin and dalteparin), or fondaparinux is administered initially, while warfarin therapy is commenced (this may take several days, usually while the patient is in hospital). 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. If another episode of PE occurs under warfarin treatment, the INR window may be increased to e.g. 2.5-3.5 (unless there are contraindications) or anticoagulation may be changed to a different anticoagulant e.g. low molecular weight heparin. In patients with an underlying malignancy, therapy with a course of low molecular weight heparin may be favored over warfarin based on the results of the CLOT trial.[19] Similarly, pregnant women are often maintained on low molecular weight heparin to avoid the known teratogenic effects of warfarin.

Warfarin therapy is usually continued for 3-6 months, or "lifelong" if there have been previous DVTs or PEs, or none of the usual risk factors is present. 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.[20]

Used inferior vena cava filter, presented with a British twenty pence coin for scale.

Inferior vena cava filter

If anticoagulant therapy is contraindicated and/or ineffective an inferior vena cava filter may be implanted.[21]

Thrombolysis

Thrombolysis can be given for severe PEs when surgery is not immediately available or possible (e.g. periarrest 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.[22] The use of thrombolysis in moderate PEs is still debatable. The aim of the therapy is to dissolve the clot, but there is an attendant risk of bleeding or stroke.[23]

Surgical management of PE

Surgical management of acute pulmonary embolism (pulmonary thrombectomy) is uncommon and has largely been abandoned because of poor long-term outcomes. However, recently, it has gone through a resurgence with the revision of the surgical technique and is thought to benefit selected patients.[24]

Chronic pulmonary embolism leading to pulmonary hypertension (known as chronic thromboembolic hypertension) is treated with a surgical procedure known as a pulmonary thromboendarterectomy.

Prognosis

Mortality from untreated PE is said to be 26%. This figure comes from a trial published in 1960 by Barrit and Jordan,[25] which compared anticoagulation against placebo for the management of PE. Barritt and Jordan performed their study in the Bristol Royal Infirmary in 1957. This study is the only placebo controlled trial ever to examine the place of anticoagulants in the treatment of PE, the results of which were so convincing that the trial has never been repeated as to do so would be considered unethical. That said, the reported mortality rate of 26% in the placebo group is probably an overstatement, given that the technology of the day may have detected only severe PEs.

Prognosis depends on the amount of lung that is affected and on the co-existence of other medical conditions; chronic embolisation to the lung can lead to pulmonary hypertension. There is controversy over whether or not small subsegmental PEs need to be treated at all[26] and some evidence exists that patients with subsegmental PEs may do well without treatment.[27][13]

Predicting mortality

The PESI and Geneva prediction rules can estimate mortality and so may guide selection of patients who can be considered for outpatient therapy.[28]

Evaluation for underlying causes for recurrence

After a first PE, the search for secondary causes is usually brief. Only when a second PE occurs, and especially when this happens while still under anticoagulant therapy, a further search for underlying conditions is undertaken. This will include testing ("thrombophilia screen") for Factor V Leiden mutation, antiphospholipid antibodies, protein C and S and antithrombin levels, and later prothrombin mutation, MTHFR mutation, Factor VIII concentration and rarer inherited coagulation abnormalities.

References

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2. Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J (1998). "Use of a clinical model for safe management of patients with suspected pulmonary embolism". Ann Intern Med 129 (12): 997-1005. PMID 9867786. 
3. Wells P, Anderson D, Rodger M, Ginsberg J, Kearon C, Gent M, Turpie A, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J (2000). "Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer.". Thromb Haemost 83 (3): 416-20. PMID 10744147. 
4. Wells PS, Anderson DR, Rodger M, Stiell I, Dreyer JF, Barnes D, Forgie M, Kovacs G, Ward J, Kovacs MJ (2001). "Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer". Ann Intern Med 135 (2): 98-107. PMID 11453709. 
5. Sanson BJ, Lijmer JG, Mac Gillavry MR, Turkstra F, Prins MH, Büller HR (2000). "Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group". Thromb. Haemost. 83 (2): 199-203. PMID 10739372. 
6. van Belle A, Büller H, Huisman M, Huisman P, Kaasjager K, Kamphuisen P, Kramer M, Kruip M, Kwakkel-van Erp J, Leebeek F, Nijkeuter M, Prins M, Sohne M, Tick L (2006). "Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography". JAMA 295 (2): 172-9. doi:10.1001/jama.295.2.172. PMID 16403929. 
7. Roy PM, Meyer G, Vielle B, Le Gall C, Verschuren F, Carpentier F, Leveau P, Furber A (2006). "Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism". Ann. Intern. Med. 144 (3): 157-64. PMID 16461959. 
8. Neff MJ (2003). "ACEP releases clinical policy on evaluation and management of pulmonary embolism". American family physician 68 (4): 759-60. PMID 12952389. 
9. Yap KS, Kalff V, Turlakow A, Kelly MJ (2007). "A prospective reassessment of the utility of the Wells score in identifying pulmonary embolism". Med. J. Aust. 187 (6): 333–6. PMID 17874979. 
10. Stein PD, Woodard PK, Weg JG, Wakefield TW, Tapson VF, Sostman HD, Sos TA, Quinn DA, Leeper KV, Hull RD, Hales CA, Gottschalk A, Goodman LR, Fowler SE, Buckley JD (2007). "Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II Investigators". Radiology 242 (1): 15-21. doi:10.1148/radiol.2421060971. PMID 17185658. 
11. Bounameaux H, de Moerloose P, Perrier A, Reber G (1994). "Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview". Thromb. Haemost. 71 (1): 1-6. PMID 8165626. 
12.  Schaefer-Prokop C, Prokop M (2005). "MDCT for the diagnosis of acute pulmonary embolism". European radiology 15 Suppl 4: D37-41. PMID 16479644. 
13.  Stein PD, Fowler SE, Goodman LR, et al (2006). "Multidetector computed tomography for acute pulmonary embolism". N. Engl. J. Med. 354 (22): 2317-27. doi:10.1056/NEJMoa052367. PMID 16738268. 
14. Worsley D, Alavi A, Aronchick J, Chen J, Greenspan R, Ravin C (1993). "Chest radiographic findings in patients with acute pulmonary embolism: observations from the PIOPED Study.". Radiology 189 (1): 133-6. PMID 8372182. 
15. McGinn S, White PD. Acute cor pulmonale resulting from pulmonary embolism. J Am Med Assoc 1935;104:1473–1480.
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17.  McConnell MV, Solomon SD, Rayan ME, Come PC, Goldhaber SZ, Lee RT (1996). "Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism". Am. J. Cardiol. 78 (4): 469-73. PMID 8752195. 
18.  Goldhaber SZ. Pulmonary embolism. Lancet 2004;363:1295-305. PMID 1509427.
19. 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. 
20. 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. 
21. Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, Laporte S, Faivre R, Charbonnier B, Barral F, Huet Y, Simonneau G (1998). "A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group". N Engl J Med 338 (7): 409-15. PMID 9459643. 
22. 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.
23. Dong B, Jirong Y, Liu G, Wang Q, Wu T. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev 2006;(2):CD004437. PMID 16625603.
24. Augustinos P, Ouriel K (2004). "Invasive approaches to treatment of venous thromboembolism". Circulation 110 (9 Suppl 1): I27-34. PMID 15339878. 
25.  Template:Cite journal author=DW, Jorden SC
26.  Le Gal G, Righini M, Parent F, van Strijen M, Couturaud F (2006). "Diagnosis and management of subsegmental pulmonary embolism". J Thromb Haemost 4 (4): 724-31. PMID 16634736. 
27.  Perrier A, Bounameaux H (2006). "Accuracy or outcome in suspected pulmonary embolism". N Engl J Med 354 (22): 2383-5. PMID 16738276. 
28. Jiménez D, Yusen RD, Otero R, et al (2007). "Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy". Chest 132 (1): 24-30. doi:10.1378/chest.06-2921. PMID 17625081.