Uptodate Tromboembolismo Pulmonar (TEP)   

Overview of acute pulmonary embolism Authors B Taylor Thompson, MD Charles A Hales, MD Section Editor Jess Mandel, MD Deputy Editor Kevin C Wilson, MD Last literature review version 18.2: mayo 2010 | This topic last updated: junio 4, 2010 (More) INTRODUCTION — Acute pulmonary embolism (PE) is a common and often fatal disease. Mortality can be reduced by prompt diagnosis and therapy. Unfortunately, the clinical presentation of PE is variable and nonspecific, making accurate diagnosis difficult. The incidence, natural history, pathophysiology, risk factors, symptoms, and signs, and outcomes of acute PE are reviewed here. The diagnosis and treatment of acute PE are discussed in detail elsewhere. (See "Diagnosis of acute pulmonary embolism" and "Treatment of acute pulmonary embolism".) DEFINITIONS — PE refers to obstruction of the pulmonary artery or one of its branches by material (eg, thrombus, tumor, air, or fat) that originated elsewhere in the body. This topic review focuses on PE due to thrombus. Air emboli and fat emboli are discussed elsewhere. (See "Air embolism" and "Fat embolism syndrome".) PE can be classified as acute or chronic. Patients with acute PE typically develop symptoms and signs immediately after obstruction of pulmonary vessels. In contrast, patients with chronic PE tend to develop slowly progressive dyspnea over a period of years due to pulmonary hypertension. (See "Clinical manifestations and diagnosis of chronic thromboembolic pulmonary hypertension" and "Treatment of chronic thromboembolic pulmonary hypertension".) Acute PE can be further classified as massive or submassive: 

 

Massive PE causes hypotension, defined as a systolic blood pressure 15 minutes. It should be suspected anytime there is hypotension accompanied by an elevated central venous pressure (or neck vein distension), which is not otherwise explained by acute myocardial infarction, tension pneumothorax, pericardial

 

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tamponade, or a new arrhythmia [1,2]. It is a catastrophic entity that frequently results in acute right ventricular failure and death. When death occurs, it is often within one to two hours of the event, although patients remain at risk for 24 to 72 hours [3,4]. The PE is frequently undiscovered until autopsy [5,6]. All acute PE not meeting the definition of massive PE are considered submassive PE.

A saddle PE is a PE that lodges at the bifurcation of the main pulmonary artery into the right and left pulmonary arteries. Most saddle PE are submassive. In a retrospective study of 546 consecutive patients with PE, 14 (2.6 percent) had a saddle PE [7]. Only two of the patients with saddle PE had hypotension. INCIDENCE — In a study of more than 42 million deaths that occurred over a 20-year duration, almost 600,000 patients (approximately 1.5 percent) had been diagnosed with PE [8]. This certainly underestimates the true incidence of PE, since more than half of all PE are probably undiagnosed. PE was the presumed cause of death in 200,000 of the cases. NATURAL HISTORY — Untreated PE is associated with a mortality rate of approximately 30 percent [8-11]. Recurrent embolism is the most common cause of death. The rate of morbidity among untreated survivors is unknown, but appears to be high. Outcomes following treatment are described below. (See 'Outcomes' below.) PROGNOSIS — Early in the course of a patient with an acute PE, certain factors can be detected or measured that may suggest that the patient is at increased risk for mortality. RV dysfunction — RV dysfunction due to PE predicts increased PE-related mortality if normotensive and hypotensive patients are considered together [10,12]. This was illustrated by a meta-analysis of seven studies (3395 normotensive or hypotensive patients with PE), which found that RV dysfunction was associated with a two-fold increase in PE-related mortality [12]. The ability of RV dysfunction to predict mortality in patients who do not have hypotension is uncertain because there are contradicting data. In the meta-analysis discussed above, analysis of only normotensive patients found that RV dysfunction correlated poorly with PE-related hospital mortality [12]. In contrast, another meta-analysis found that RV dysfunction was associated with a two- to three-fold increase in mortality in hemodynamically stable patients [13]. The different outcomes may be due, in part, to the way that RV function was determined. The first meta-analysis assessed RV function echocardiographically, whereas the second assessed RV function via echocardiography or computed tomography.

 

 

RV dysfunction may also predict recurrent PE or DVT. In a prospective cohort study, 301 patients who had experienced their first PE were categorized as having no RV dysfunction, RV dysfunction with regression (ie, present at admission but not at discharge), or persistent RV dysfunction [14]. During a mean follow up of three years, patients with persistent RV dysfunction were more likely to have a recurrent PE, recurrent DVT, or PE-related death, compared to patients with no RV dysfunction or RV dysfunction with regression. Brain natriuretic peptides — An elevated brain natriuretic peptide (BNP) or N-terminal probrain natriuretic peptide (NT-proBNP) predicts RV dysfunction and mortality, according to three meta-analyses [15-17]. As an example, a meta-analysis of 16 studies found that shortterm mortality was increased 6-times among patients with a BNP >100 pg/mL and 16-times among patients with an NT-proBNP >600 ng/L [15]. BNP and NT-proBNP may predict other adverse outcomes. In an observational study of 73 consecutive patients diagnosed with acute PE, serum BNP levels >90 pg/mL (drawn within four hours of presentation) were associated with cardiopulmonary resuscitation, mechanical ventilation, vasopressor therapy, thrombolysis, and embolectomy, as well as death [18]. Serum BNP levels 0.07 mcg/L plus an NT-proBNP level ≥600 ng/L was associated with a higher 40-day mortality than a troponin T level >0.07 mcg/L plus an NT-proBNP level 25 cigarettes per day), and hypertension [37]. SYMPTOMS / SIGNS — Specific symptoms and signs are not helpful diagnostically because their frequency is similar among patients with and without PE. In the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II), the following frequencies of symptoms and signs were noted among patients with PE who did not have preexisting cardiopulmonary disease [32,38]: 

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The most common symptoms were dyspnea at rest or with exertion (73 percent), pleuritic pain (44 percent), cough (34 percent), >2-pillow orthopnea (28 percent), calf or thigh pain (44 percent), calf or thigh swelling (41 percent), and wheezing (21 percent) [32]. The onset of dyspnea was usually within seconds (46 percent) or minutes (26 percent). The most common signs were tachypnea (54 percent), tachycardia (24 percent), rales (18 percent), decreased breath sounds (17 percent), an accentuated pulmonic component of the second heart sound (15 percent), and jugular venous distension (14 percent) [32]. Circulatory collapse was uncommon (8 percent) [32]. Among such patients, dyspnea was present in 82 percent and either dyspnea or tachypnea was present in 91 percent. Massive PE may be accompanied by acute right ventricular failure,

 

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manifested by increased jugular venous pressure, a right-sided S3, and a parasternal lift. Symptoms or signs of lower extremity deep venous thrombosis (DVT) were common (47 percent) [32]. They included edema, erythema, tenderness, or a palpable cord in the calf or thigh.

It is important to realize that pulmonary embolism is frequently asymptomatic. This was demonstrated by a systematic review of 28 studies that found that among the 5233 patients who had a deep vein thrombosis, 1665 (32 percent) had asymptomatic PE [39]. DIAGNOSIS — The symptoms and signs of PE are highly variable, nonspecific, and common among patients with and without PE [1,40]. Thus additional testing is needed to confirm or exclude the diagnosis of PE [1]. The diagnosis of acute PE is discussed in detail elsewhere. (See "Diagnosis of acute pulmonary embolism".) TREATMENT — Anticoagulation is the mainstay of therapy for acute PE. Other treatment strategies include thrombolysis, inferior vena caval filters, and embolectomy. Treatment of acute PE is discussed in detail elsewhere. (See "Treatment of acute pulmonary embolism" and "Anticoagulation in acute pulmonary embolism" and "Fibrinolytic (thrombolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis".) Outcomes — Effective anticoagulant therapy decreases the mortality rate from approximately 30 percent to 2 to 8 percent [8-11]. However, morbidity is common among survivors. Pulmonary hypertension is a consequence of acute PE, as illustrated by an observational study that included 144 patients with confirmed PE who were treated with heparin [41]. Approximately 50 percent of the patients had persistent or worsened elevation of their right ventricular systolic pressure six months after their acute PE, suggesting pulmonary hypertension. This was frequently accompanied by dyspnea at rest and/or exercise intolerance. The likelihood of morbidity and mortality following treatment may be influenced by whether the acute PE occurred in the absence of risk factors or predisposing illnesses (ie, unprovoked PE). An observational study that followed 308 consecutive patients who were being treated for an acute PE (median duration of follow-up was 3.3 years) found that patients with unprovoked PE were more likely to develop recurrent PE, chronic thromboembolic pulmonary hypertension, malignancy, or cardiovascular events than patients with risk factors for PE [42]. In contrast, patients with risk factors had a higher risk for mortality.

 

 

INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. (See "Patient information: Pulmonary embolism".) We encourage you to print or e-mail this topic, or to refer patients to our public web site www.uptodate.com/patients, which includes this and other topics. SUMMARY AND RECOMMENDATIONS 

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Acute pulmonary embolism (PE) is a common and often fatal disease. It can be classified as massive or submassive. Massive acute PE causes hypotension, defined as a systolic blood pressure 15 minutes. All acute PE not meeting the definition of massive PE are considered submassive PE. (See 'Definitions' above.) Acute PE is associated with a mortality rate of approximately 30 percent without treatment, primarily due to recurrent embolism. However, accurate diagnosis followed by effective anticoagulant therapy decreases the mortality rate to 2 to 8 percent. (See 'Natural history' above and 'Outcomes' above.) Factors that promote the development of deep vein thrombosis also increase the risk for PE. (See 'Risk factors' above and "Overview of the causes of venous thrombosis".) The most common symptoms of acute PE are dyspnea at rest or with exertion, pleuritic pain, cough, >2-pillow orthopnea, calf or thigh pain or swelling, and wheezing. The most common signs are tachypnea, tachycardia, rales, decreased breath sounds, an accentuated pulmonic component of the second heart sound, and jugular venous distension. (See 'Symptoms / Signs' above.) The symptoms and signs of PE are highly variable, nonspecific, and common among patients with and without PE. Thus, additional testing is needed to confirm or exclude the diagnosis of PE. (See 'Diagnosis' above and "Diagnosis of acute pulmonary embolism".) Anticoagulation is the mainstay of therapy for acute PE. Other treatment strategies include thrombolysis, inferior vena caval filters, and embolectomy. (See 'Treatment' above and "Treatment of acute pulmonary embolism".)

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19. Jimenez, D, Aujesky, D, Diaz, G, et al. Prognostic significance of deep vein thrombosis in patients presenting with acute symptomatic pulmonary embolism. Am J Respir Crit Care Med 2010; 181:983. 20. Torbicki, A, Galie, N, Covezzoli, A, et al. Right heart thrombi in pulmonary embolism: results from the International Cooperative Pulmonary Embolism Registry. J Am Coll Cardiol 2003; 41:2245. 21. Becattini, C, Vedovati, MC, Agnelli, G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 2007; 116:427. 22. Jimenez, D, Uresandi, F, Otero, R, et al. Troponin-based risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis. Chest 2009; 136:974. 23. Janata, KM, Leitner, JM, Holzer-Richling, N, et al. Troponin T predicts in-hospital and 1-year mortality in patients with pulmonary embolism. Eur Respir J 2009; 34:1357. 24. Kostrubiec, M, Pruszczyk, P, Bochowicz, A, et al. Biomarker-based risk assessment model in acute pulmonary embolism. Eur Heart J 2005; 26:2166. 25. Kistner, RL, Ball, JJ, Nordyke, RA, Freeman, GC. Incidence of pulmonary embolism in the course of thrombophlebitis of the lower extremities. Am J Surg 1972; 124:169. 26. Moser, KM, LeMoine, JR. Is embolic risk conditioned by localization of deep venous thrombosis? Ann Intern Med 1981; 94:439. 27. Weinmann, EE, Salzman, EW. Deep-vein thrombosis. N Engl J Med 1994; 331:1630. 28. Moser, KM. Venous thromboembolism. Am Rev Respir Dis 1990; 141:235. 29. Nakos, G, Kitsiouli, EI, Lekka, ME. Bronchoalveolar lavage alterations in pulmonary embolism. Am J Respir Crit Care Med 1998; 158:1504. 30. Benotti, JR, Dalen, JE. The natural history of pulmonary embolism. Clin Chest Med 1984; 5:403. 31. Girard, P, Decousus, M, Laporte, S, Buchmuller, A. Diagnosis of pulmonary embolism in patients with proximal deep vein thrombosis: specificity of symptoms and perfusion defects at baseline and during anticoagulant therapy. Am J Respir Crit Care Med 2001; 164:1033. 32. Stein, PD, Beemath, A, Matta, F, et al. Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. Am J Med 2007; 120:871. 33. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990; 263:2753. 34. Darze, ES, Latado, AL, Guimaraes, AG, et al. Incidence and clinical predictors of pulmonary embolism in severe heart failure patients admitted to a coronary care unit. Chest 2005; 128:2576. 35. Heit, JA, O'Fallon WM, Petterson, TM, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med 2002; 162:1245.  

 

36. Pulido, T, Aranda, A, Zevallos, MA, et al. Pulmonary embolism as a cause of death in patients with heart disease: an autopsy study. Chest 2006; 129:1282. 37. Goldhaber, SZ, Grodstein, F, Stampfer, MJ, et al. A prospective study of risk factors for pulmonary embolism in women. JAMA 1997; 277:642. 38. Stein, PD, Fowler, SE, Goodman, LR, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 2006; 354:2317. 39. Stein, PD, Matta, F, Musani, MH, Diaczok, B. Silent pulmonary embolism in patients with deep venous thrombosis: a systematic review. Am J Med 2010; 123:426. 40. Le Gal, G, Testuz, A, Righini, M, et al. Reproduction of chest pain by palpation: diagnostic accuracy in suspected pulmonary embolism. BMJ 2005; 330:452. 41. Kline, JA, Steuerwald, MT, Marchick, MR, et al. Prospective evaluation of right ventricular function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or subsequent elevation in estimated pulmonary artery pressure. Chest 2009; 136:1202. 42. Klok, FA, Zondag, W, van Kralingen, KW, et al. Patient outcomes after acute pulmonary embolism: a pooled survival analysis of different adverse events. Am J Respir Crit Care Med 2010; 181:501.  

 

 

 

Diagnosis of acute pulmonary embolism Authors B Taylor Thompson, MD Charles A Hales, MD Section Editor Jess Mandel, MD Deputy Editor Kevin C Wilson, MD Last literature review version 18.2: mayo 2010 | This topic last updated: mayo 25, 2010 (More) INTRODUCTION — Acute pulmonary embolism (PE) is a common and often fatal disease. Mortality can be reduced by prompt diagnosis and therapy. Unfortunately, the clinical presentation of PE is variable and nonspecific; thus, diagnostic testing is necessary before confirming or excluding the diagnosis of PE. Diagnosis of PE is discussed in detail here. The epidemiology, prognosis, pathophysiology, risk factors, symptoms, and signs of PE are reviewed elsewhere. In addition, the treatment of PE is discussed separately. (See "Overview of acute pulmonary embolism" and "Treatment of acute pulmonary embolism" and "Fibrinolytic (thrombolytic) therapy in acute pulmonary embolism and lower extremity deep vein thrombosis".) DIAGNOSTIC TESTS — Many of the symptoms and signs detected in patients with acute PE are also common among patients without PE (table 1), emphasizing the need for additional evaluation. Below we summarize the major diagnostic tests employed in the evaluation of a patient with suspected PE. Laboratory — Routine laboratory findings are nonspecific. They include leukocytosis, an increased erythrocyte sedimentation rate (ESR), and an elevated serum LDH or AST (SGOT) with a normal serum bilirubin. Arterial blood gas — Arterial blood gas (ABG) measurements and pulse oximetry have a limited role in diagnosing PE [1]. ABGs usually reveal hypoxemia, hypocapnia, and respiratory alkalosis. Patients with room air pulse oximetry readings 8 hrs) Quantitative rapid ELISA (results in 30 min) Semi-quantitative rapid ELISA (results in 10 min) Qualitative rapid ELISA (results in 10 min) Quantitative latex agglutination assay (results in 10 to 15 min) Semi-quantitative latex agglutination assay (results in 5 min) Erythrocyte agglutination assay (SimpliRED) (results in 2 min)

For the quantitative assays, a level >500 ng/mL is usually considered abnormal [31].

 

 

D-dimer assays for the diagnosis of PE have been extensively studied. They are best characterized as having good sensitivity and negative predictive value, but poor specificity and positive predictive value. Sensitivity — D-dimer levels are abnormal in approximately 95 percent of all patients with PE when measured by ELISA, quantitative rapid ELISA, or semi-quantitative rapid ELISA [31]. This falls to approximately 90 percent when measured by qualitative rapid ELISA or quantitative latex agglutination, 86 percent when measured by semi-quantitive latex agglutination, and 82 percent when measured by erythrocyte agglutination [31]. Among patients who have subsegmental PE, D-dimer levels are abnormal in only 50 percent when measured by quantitative latex agglutination [32]. Specificity — D-dimer levels are normal in only 40 to 68 percent of patients without PE, regardless of the assay used [31]. This is a consequence of abnormal D-dimer levels being common among hospitalized patients, especially those with malignancy or recent surgery (table 3) [33-35]. The specificity decreases even further in the setting of severe renal dysfunction (ie, GFR