PULMONARY EMBOLISM

Background: Pulmonary embolism (PE) is a common and potentially lethal disease; unfortunately, the diagnosis is often missed because patients with PE present with nonspecific signs and symptoms. If left untreated, approximately one third of patients who survive an initial PE subsequently die from a future embolic episode. Most patients succumb to PE within the first few hours of the event. In patients who survive, recurrent embolism and death can be prevented with prompt diagnosis and therapy.
The mortality and morbidity rates from venous thromboembolism are best described by Ken Moser in 2 words: substantial and unacceptable. In the 1940s, Bauer performed fundamental studies that led to the current understanding of the pathogenesis of deep vein thrombosis (DVT). Subsequently, Savitt and Gallagher performed autopsy-based studies of the prevalence of venous thromboembolism in patients who had lower extremity fractures and other risk factors for PE. The most important conceptual advance that occurred over the last several decades is that PE is not a disease; rather, it is a complication of DVT.
Virtually every physician who is involved in patient care (eg, internist, generalist, orthopedic surgeon, gynecologic surgeon, urologic surgeon, pulmonary subspecialist, cardiologist) encounters patients who are at risk of venous thromboembolism.
History: The presentation of pulmonary embolism (PE) may vary from a sudden onset of catastrophic hemodynamic collapse to gradually progressive dyspnea. The diagnosis of PE should be sought actively in patients with respiratory symptoms unexplained by an alternate diagnosis. The symptoms of PE are nonspecific; therefore, a high index of suspicion is required, particularly when a patient has risk factors, which include recent surgery, immobility, or a hypercoagulable state.
The presentation of patients with PE can be categorized into 4 classes based on the acuity and severity of pulmonary arterial occlusion. These categories are (1) massive PE, (2) acute pulmonary infarction, (3) acute embolism without infarction, and (4) multiple pulmonary emboli.
• Massive pulmonary embolism
o Large emboli compromise sufficient pulmonary circulation to produce circulatory collapse and shock.
o The patient has hypotension; appears weak, pale, sweaty, and oliguric; and develops impaired mentation.
• Acute pulmonary infarction
o Approximately 10% of patients have peripheral occlusion of a pulmonary artery causing parenchymal infarction.
o These patients present with acute onset of pleuritic chest pain, breathlessness, and hemoptysis.
o Although the chest pain may be indistinguishable from ischemic myocardial pain, normal electrocardiogram findings and no response to nitroglycerine rules it out.
• Acute embolism without infarction: Patients have nonspecific symptoms of unexplained dyspnea and/or substernal discomfort.
• Multiple pulmonary emboli
o This group consists of 2 subsets of patients.
o The first subset has repeated documented episodes of pulmonary emboli over years, eventually presenting with signs and symptoms of pulmonary hypertension and cor pulmonale.
o The second subset has no previously documented pulmonary emboli but have widespread obstruction of the pulmonary circulation with clot. They present with gradually progressive dyspnea, intermittent exertional chest pain, and, eventually, features of pulmonary hypertension and cor pulmonale.
• Most patients with PE have no obvious symptoms at presentation. In contrast, patients with symptomatic deep vein thrombosis (DVT) commonly have PE confirmed on diagnostic studies in the absence of pulmonary symptoms.
• The most common symptoms of PE in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study were dyspnea (73%), pleuritic chest pain (66%), cough (37%), and hemoptysis (13%).
• Patients with PE may present with atypical symptoms, where strong suspicion in a high-risk patient often leads to consideration of PE in the differential diagnosis. These symptoms include the following:
o Seizures
o Syncope
o Abdominal pain
o Fever
o Productive cough
o Wheezing
o Decreasing level of consciousness
o New onset of atrial fibrillation
• Pleuritic chest pain without other symptoms or risk factors may be a presentation of PE.
Physical: The physical examination is quite variable in PE and, for convenience, may be grouped into 4 categories as follows:
• Massive pulmonary embolism
o These patients are in shock. They have systemic hypotension, poor perfusion to the extremities, tachycardia, and tachypnea.
o Additionally, signs of pulmonary hypertension such as palpable impulse over second left interspace, loud P2, right ventricular S3 gallop, and a systolic murmur louder on inspiration at left sternal border (tricuspid regurgitation) may be present.
• Acute pulmonary infarction
o These patients have decreased excursion of involved hemithorax, palpable or audible pleural friction rub, and even localized tenderness.
o Signs of pleural effusion, such as dullness upon percussion and diminished breath sounds, may be present.
• Acute embolism without infarction
o These patients have nonspecific physical signs that may easily be secondary to another disease process.
o Tachypnea and tachycardia frequently are detected, pleuritic pain sometimes may be present, crackles may be heard in the area of embolization, and local wheeze may be heard rarely.
• Multiple pulmonary emboli or thrombi
o Patients belonging to both the subsets in this category have physical signs of pulmonary hypertension and cor pulmonale.
o Patients may have elevated jugular venous pressure, right ventricular heave, palpable impulse in the left second intercostal space, right ventricular S3 gallop, systolic murmur over the left sternal border that is louder during inspiration, hepatomegaly, ascites, and dependent pitting edema.
o These findings are not specific for PE and require a high index of suspicion for pursuing appropriate diagnostic studies.
• The most common physical signs in the PIOPED study were as follows:
o Tachypnea (70%)
o Rales (51%)
o Tachycardia (30%)
o Fourth heart sound (24%)
o Accentuated pulmonic component of the second heart sound (23%)
• Fever of less than 39°C may be present in 14% of patients; however, temperature higher than 39.5°C is not from PE.
• Chest wall tenderness upon palpation, without a history of trauma, may be the sole physical finding in rare cases.
Causes: The causes for PE are multifactorial and are not readily apparent in many cases. The following causes have been described in the literature:
• Venous stasis
o Venous stasis leads to accumulation of platelets and thrombin in veins.
o Increased viscosity may occur due to polycythemia and dehydration, immobility, raised venous pressure in cardiac failure, or compression of a vein by a tumor.
• Hypercoagulable states
o The complex and delicate balance between coagulation and anticoagulation is altered by many diseases, by obesity, after surgery, or by trauma.
o Concomitant hypercoagulability may be present in disease states where prolonged venous stasis or injury to veins occurs.
o Hypercoagulable states may be acquired or congenital. Factor V Leiden mutation causing resistance to activated protein C is the most common risk factor. Factor V Leiden mutation is present in up to 5% of the normal population and is the most common cause of familial thromboembolism.
o Primary or acquired deficiencies in protein C, protein S, and antithrombin III are other risk factors. The deficiency of these natural anticoagulants is responsible for 10% of venous thrombosis in younger people
• Immobilization
o Immobilization leads to local venous stasis by accumulation of clotting factors and fibrin, and a thrombus is synthesized.
o The risk of PE increases with prolonged bed rest or immobilization of a limb with plaster.
o Paralysis increases the risk.
• Surgery and trauma
o Both surgical and accidental trauma predispose patients to venous thromboembolism by activating clotting factors and causing immobility.
o Fractures of the femur and tibia are associated with the highest risk, followed by pelvic, spinal, and other fractures.
o Severe burns carry a high risk of DVT or PE.
o A recent study by Greets in 1994 indicated that major trauma was associated with a 58% incidence rate of DVT, 18% of these were in proximal veins.
o PE may account for 15% of all postoperative deaths. Leg amputations and hip, pelvic, and spinal surgery are associated with the highest risk.
• Pregnancy
o The incidence of thromboembolic disease in pregnancy has been reported to range from 1 case in 200 deliveries to 1 case in 1400 deliveries.
o Fatal events may occur rarely, 1-2 cases per 100,000 pregnancies.
o The mechanism of DVT is venous stasis, decreasing fibrinolytic activity, and increased procoagulant factors.
• Oral contraceptives and estrogen replacement
o Estrogen-containing birth control pills have increased the occurrence of venous thromboembolism in healthy women.
o The risk is proportional to the estrogen content and is increased in postmenopausal women on hormonal replacement therapy.
o The relative risk is 3-fold, but the absolute risk is 20-30 cases per 100,000 persons per year.
• Malignancy
o Malignancy has been identified in 17% of patients with venous thromboembolism.
o The neoplasms most commonly associated with PE, in descending order of frequency, are pancreatic carcinoma; bronchogenic carcinoma; and carcinoma of the genitourinary tract, colon, stomach, and breast.
• Other recognized risk factors include the following:
o Stroke
o Indwelling venous catheters
o Previous history of venous thromboembolism
o Congestive heart failure
o Fractures of the long bone
o Obesity
o Pregnancy
o Varicose veins
o Inflammatory bowel disease