An obstruction of the pulmonary arteries caused by a blood clot (embolus) or other material curried to the pulmonary vasculature by Ihe circulatory system. Although a blood clot is the most common cause of pulmonary embolism, air, fat, bone marrow, foreign bodies, amniotic fluid, and tumor cells also can obstruct the pulmonary vessels.
Common but difficult to diagnose, pulmonary embolism can be effectively heated. In the USA, the incidence is about 650,000 cases annually. Pulmonary embolism is estimated to be the primary cause of death in 100,000 persons and a contributory factor in perhaps another 100.000 deaths annually. Statistics for the elderly are not available. Because the symptoms and signs are nonspecific, pulmonary embolism may be overdiagnosed or underdiagnosed, especially in the elderly. Perhaps 30% of cases are misdiagnosed, with overdiagnosis particularly common in patients who have cardiac and other respiratory conditions, as elderly patients frequenlly do. Accurate diagnosis minimizes the risks of both untreated pulmonary embolism and unnecessary anticoagulant therapy.
Pathophysiology
About 90%’ ol blood clots that cause pulmonary embolism originate in the legs. The risk that a clot will embolize and lodge in the lung is greater if it is in the popliteal or iliofemoral vein (about 50%) than if it is in the calf veins (< 5%). Other, less common sites of thrombosis that may give rise to pulmonary embolism arc the right atrium: the right ventricle; and the pelvic, renal, hepatic, subclavian, and .jugular veins. Risk factors for venous thrombosis are vessel wall injury, stasis, and conditions thai increase Ihe tendency of the blood to clot, including deficiencies of antithrombin 111, protein C, and protein S, as well as disseminated intravascular coagulation, polycythemia vera, and presence of the lupus anticoagulant or anli-cardiolipin antibody. Common medical conditions (eg. trauma to leg vessels, obesity, heart failure, malignancy, hip fracture, and myeloproliferative disorders) also predispose a person to venous thrombosis, as do estrogen use, the presence of a femoral venous calheler. surgery, and immobility, which is common among the elderly.
Symptoms and Signs
The degree of pulmonary vascular obstruction caused by the embolus and the patient's prior cardiopulmonary function affect the symptoms and signs. Patients who have small thromboemboli may be asymptomatic, although asymptomatic pulmonary embolism is rare in the elderly. In the general population, the most common symptoms are shortness of breath (80%), chest pain that may be pleurilic (70%). anxiety (60%). leg pain or swelling (40%), hemoptysis (35%). and syncope (15%). The most common physical findings are tachypnea (90%), tachycardia (50%'). fever (40%). leg edema or tenderness (33%), cyanosis (20%), and a pleural friction rub (18%). Percentages for the elderly are not available. Although most patients with pulmonary embolism have deep venous thrombosis, only 33% have clinical signs of thrombosis—eg, leg swelling, tenderness, increased warmth, or Homans' sign.
Patients with pulmonary embolism usually present wilh one of Ihe following patterns: (1) diagnostically confusing syndromes (confusion, unexplained fever, wheezing, resistant heart failure, or unexplained arrhythmias); (2) transient shortness of breath and tachypnea only; (3) pulmonary infarction (pleuritic pain, cough, hemoptysis, pleural effusion, and pulmonary infiltrate); (4) right-sided heart failure with shortness of brealh and tachypnea; or (5) cardiovascular collapse with hypotension and syncope. Less than 20% of patients have Ihe classic triad of dyspnea, chest pain, and hemoptysis. However, most patients do have tachypnea (respiratory rate > 16/min), shortness of breath, and chest discomfort. In fact, if tachypnea is absent, pulmonary embolism is unlikely.
About 33% of patients with pulmonary embolism have pleural effusions, which are usually unilateral but may be bilateral. About 67% are bloody (RBCs>1U0,000/pL>. The differential diagnosis of bloody effusion is limited to three principal conditions: pulmonary embolism, cancer, and trauma. Patients with pulmonary embolism and a bloody pleural effusion generally have a pulmonary infiltrate on chest x-ray that suggests hemorrhagic consolidation of the lung parenchyma. Most of these patients have only pulmonary hemorrhage, and the infiltrate resolves over several days. About 10% of patients with pulmonary emboli, especially those with severe heart failure, develop pulmonary infarction. About 67% of nonbloody effusions due to pulmonary embolism are exudates wilh elevated WBC counts (up to 75,QQQ/(iL), which mimic infected pleural effusions.
Mechanical obstruction of part of the pulmonary circulation may lead to increased pulmonary vascular resistance, although vasoconstriction secondary to alveolar capillary hypoxemia and mediator release may contribute. This increased resistance causes right ventricular and pulmonary arterial pressures to increase in order to maintain cardiac output. In patients with no prior cardiopulmonary disease, the pulmonary arterial pressure correlates with the percentage of the pulmonary vascular bed occluded by the emboli. Thus, pulmonary hypertension (> 25 mm Hg) in a patient with previously normal heart and lungs indicates extensive obstruction (> 40% to 50%) of the pulmonary vascular bed. However, in patients with prior cardiopulmonary disease, the pulmonary arterial pressure does not correlate with the percentage of vascular bed obstruction. In these patients, a small clot may be enough to produce a marked hemodynamic effect because of the limited cardiac reserve.
Syncope, a systolic blood pressure < 100 mm Hg, or a marked decrease in the systolic blood pressure in a hypertensive patient suggests the possibility of a massive pulmonary embolism or a hemodynamically significant embolus in a patient wilh marginal cardiopulmonary function. When a sudden increase in pulmonary vascular resistance prevents the right ventricle from generating sufficient forward flow, right ventricular failure, decreased cardiac output, and hypotension result. The latter is ominous because the decrease in aortic diastolic pressure may significantly reduce coronary blood flow to the overworked right ventricle, establishing a vicious circle.
A patient who is hypotensive because of pulmonary embolism will have elevated right atrial and ventricular pressures (as measured by a Swan-Ganz catheter). Thus, a normal right atrial or ventricular pressure in a patient with hypotension excludes pulmonary embolism as the cause.
Laboratory Findings
After a history is obtained and a physical examination is performed on a patient with suspected pulmonary embolism, a chest x-ray, an ECG, and arterial blood gas values should be obtained. If pulmonary embolism is still considered likely, the next step is usually to obtain a ventilation-perfusion lung scan. If deep venous thrombosis is strongly suspected or if the lung scan is likely to be indeterminate (because of underlying lung disease), an alternative approach might be to order an impedance plethysmogram or a venogram. However, the gold standard for diagnosing pulmonary embolism is pulmonary angiography.
Chest x-rafS: Chest x-rays may be normal or may show nonspecific abnormalities, eg, atelectasis, an elevated hemidiaphragm, pleural effusion, or an infiltrate. Findings such as an enlarged pulmonary artery on one sidcorhyperlucency of one lung because of reduced pulmonary vascular markings are infrequent. Such findings are more commonly produced by rotation of the patient than by pulmonary embolism. However, a plcural-based pyramidal infiltrate lhat points toward the hilus (Hampton hump) is an infrequent finding that suggests pulmonary embolism. Although the chest x-ray cannot establish or exclude a diagnosis of pulmonary embolism, it can help diagnose other conditions thai may explain the patient's symptoms, eg, pneumothorax, rib fracture, or heart failure.
Electrocardiography: Generally ECG findings arc nonspecific; as many as 33% of patients with pulmonary embolism have a normal ECO. The most common abnormal findings are sinus tachycardia and nonspecific ST-segmcnt and T-wave changes. Infrequent changes that strongly suggest pulmonary embolism indicate strain on the right side of the heart; these changes include T-wave inversion in precordial leads Vi to V4. transient right bundle branch block, right or lefl deviation of the QRS axis, sudden onset of atrial fibrillation or other atrial arrhythmia, and ECG signs of right ventricular hypertrophy or right atrial enlargement. The S1Q.1T3 pattern (deep S wave in lead I and a new 0 wave and inverted T wave in lead III) also suggests pulmonary embolism. This pattern of right-sided heart strain is usually accompanied by T-wave inversion in the precordial leads.
Arterial blood gas studies: Pulmonary embolism often resulls in arterial hypoxemia because a low venlilaiion-perfusion ratio develops secondary to airway closure and bronchoconstriction in lung segments adjacent to the emboli. Intrapulmoiiary shunting of blood and a reduced mixed venous oxygen tension also contribute to the arterial hypoxemia. Rarely, righl-lo-left shunting of blood may occur because of a patent foramen ovale due to right atrial hypertension from massive pulmonary embolism. Of course, in very old people without pulmonary embolism, a decreased PaCb may not indicate disease.
Although pulmonary embolism often causes marked hypoxemia, some elderly patients with pulmonary embolism may have a PaO; of > 70 mm Hg while breathing room air. Therefore, a normal Pa<>> does not exclude an embolus. Perhaps more significant is a sudden decrease in Paoi that cannot be easily explained by another diagnosis. Because pulmonary embolism generally causes tachypnea and respiratory alkalosis, arterial blood gas values typically show a decrease in PaCOj.
Lung SCBn: A lung scan showing no perfusion defect excludes pulmonary embolism. One showing a perfusion defect as large as or larger than a lung segment without a malching ventilation defect indicates an 85% to 90% probability of pulmonary embolism. Such a scan with a matching ventilation defect indicates a 30% to 45% likelihood of pulmonary embolism.
A lung scan with a subsegmental perfusion defect, with or without a matching ventilation defect, is often labeled a low-probability scan, but the probabilily of pulmonary embolism is still 20% lo 30%. The lung scan is termed indeterminate if matching ventilation and perfusion defects correspond with an infiltrate on the chest x-ray; this type of scan has a 25% lo 40% association with pulmonary embolism.
Pulmonary angiography: As mentioned, pulmonary angiography is the gold standard for diagnosing pulmonary embolism. Two findings are pathognomonic: a constant intraluminal filling defect and a sharp cul-off of a vessel. Experimental studies designed to lesl Ihe sensitivity of pulmonary angiography indicate that a single, small embolus may be missed but that many emboli rarely are missed. Because most palients with pulmonary embolism have many emboli, the incidence of false-negative pulmonary angiograms is believed to be low. Follow-up clinical and laboratory studies in patients with negative pulmonary angiograms also suggest that false-negative angiograms are rare.
Pulmonary angiography is safe for patients who do not have severe pulmonary hypertension or cardiopulmonary decompensation. These conditions, which increase the risk of the procedure, are relative contraindications, When performed by an experienced angiographer. the procedure is associated with minimal morbidity and a mortality rate of only about 0.2%. However, the dye can induce significant renal injury, so patients should be well hydrated, and the use of mannitol should be considered. Several authorities believe that in an elderly palient, the risks associated with anlicoagulation exceed those associated with pulmonary angiography performed by an experienced examiner.
Venography and impedance plethysmography: Venography is the gold standard for diagnosing venous thrombosis, although it may be impossible to perform in patients who have significant edema. Side effects. including allergic reactions and Ihrombophlebitis. occur in 2% of patients.
Impedance plethysmography, combined with Doppler ultrasonography, is a helpful noninvasive diagnostic test for deep venous thrombosis. Studies correlating resulls of impedance plethysmography with venography indicate that impedance plethysmography has a sensitivity of 86%), a specificity of 97%, a positive predictive value of 97%, and a negative predictive value of 85%. Impedance plethysmography is an excellent procedure for delecting aelol in the popliteal or iliofemoral vein, but it can miss a clot in the calf veins. Fortunately, the risk of pulmonary embolism from a clot confined to the calf veins is small. However, a calf-vein clol can exlend into the popliteal and femoral systerns, where the risk of pulmonary embolism is much higher. Serial impedance plethysmograms may be needed to exclude extension of a calf-vein clot.
Because 33% of people with negative pulmonary angiography findings have deep venous thrombosis, venography or impedance plethysmography can provide useful therapeutic information. Although these tests can help diagnose peripheral dots, they cannot directly establish the diagnosis of pulmonary embolism.
Digital subtraction angiography, magnetic resonance imaging, and fiberoptic angioscopy: These tests arc being evaluated as diagnostic tools. Digital subtraction angiography and magnetic resonance imaging arc less invasive and use less dye than pulmonary angiography. Though invasive, fiberoptic angioscopy provides direct visualization of the pulmonary vessels and clot as well as a means of removing the clot.
Diagnosis
The commonly asked diagnostic question is: Does this patient have pulmonary embolism’? But prospective studies indicate that about 33% of patients wilh negative pulmonary angiography findings have deep venous thrombosis documented by venography. Therefore, a better diagnostic question would be: Does this patient have evidence of either a pulmonary embolus or venous thrombosis!
The likelihood of pulmonary embolism should be estimated using both clinical assessment and laboratory studies, including the lung scan. If the lung scan shows no perfusion abnormality, pulmonary embolism can be excluded. If the lung scan shows a perfusion defect smaller than asubsegment of the lung and the clinical likelihood of pulmonary embolism is low, many clinicians would not pursue the diagnosis further. Conversely, if the lung scan reveals a perfusion defect that is segmental or larger without a matching ventilalion defect, and the clinical likelihood of pulmonary embolism is high, most clinicians would treat the patient unless special circumstances required a definitive diagnosis by pulmonary angiography.
Prospective clinical studies indicate that about 10% of patients evaluated for pulmonary embolism have both a low-probability lung scan and an unlikely clinical assessment. At the other extreme, about 30% of patients have both a high-probability lung scan and a likely clinical assessment. Managemenl of patients at either extreme is clear, but the appropriate managemenl for the other 60% of patients is not. Several approaches are available: Obtain a pulmonary angiogram, empirically anticoagulale, obtain an impedance plethysmogram or venogram, or observe.
In patients with a low-probability lung scan, impedance plethysmography may help determine whelher anticoagulant therapy is appropriate. Generally, patients with positive impedance plethysmography results should be treated with heparin for deep venous thrombosis. In patients with less than a high-probability lung scan, only a moderate clinical probability of pulmonary embolism, an adequate cardiopulinonary reserve, and negative impedance plethysmography results, observation and serial plethysmograms may be appropriate. In general, the greater the risk of not treating the patient for pulmonary embolism or the greater the risk of therapy, the greater the need for definitive angiographic diagnosis. The elderly, especially women and those who tend to fall or confuse medications, are particularly vulnerable to the side effects of anticoagulant medications.
Prognosis
The mortality rate for patients with pulmonary embolism who receive anticoagulant therapy is only 8%; the rale for those who do not receive treatment is 30%. In the elderly, the difference between these mortality rates may be even grealer. Prognosis is poorest in patients with severe underlying cardiac or pulmonary disease. Between 75% and 90% of dealhsfrom pulmonary embolism occur within the first few hours. After that, death usually results from a recurrent embolic event.
Pulmonary embolism is believed to recur in 5% to 10% of patients despite heparin therapy. The likelihood of recurrent emboli is greatest in those who have massive pulmonary embolization and those in whom anticoagulant therapy has been inadequate. If recurrence develops in the first few days of heparin or thrombolytic therapy, treatment is usually continued. If recurrenl episodes or massive embolization occurs from a clol in the legs, interrupiion of the inferior vena cava should be considered.
The long-term prognosis for patients surviving pulmonary embolism is determined by underlying medical problems and cardiopulmonary status. Recurrent pulmonary embolism leading to chronic pulmonary hypertension and cor pulmonale is uncommon, occurring in perhaps < 2% of patients; the exact frequency in the elderly is not known.
Treatment
The general principles of therapy are to provide enough supplemental oxygen to achieve a Pap2 of 60 to 70 mm Hg, to relieve pain wilh morphine or other analgesics, to provide adequate intravascular fluid for maintaining cardiac output, to monitor the patient for evidence of bleeding from anticoagulant therapy, and (o avoid drugs that adversely affect platelet function (eg, aspirin or other cyclooxygenase blockers).
The hypotensive patient with pulmonary embolism should be treated with volume expanders, streptokinase to speed clot lysis, and an infusion of enough norepinephrine to increase aortic diastolic pressure and coronary blood flow. Studies in experimental animals indicate that norepinephrine is much more effective than volume loading or isoproterenol infusion in reversing shock in pulmonary embolism. Rarely, immediate surgery to remove a large clol from a major vessel may be attempted, but survival rates are poor.
Generally, the first medication used lo treat deep venous thrombosis or pulmonary embolism, heparin prevents clol formation and extension but does not lyse clots. Because the risk of death from pulmonary embolism is greatest in the first few hours and because diagnostic test resuits often are not available for X to 12 h, it is generally advisable to begin heparin therapy in patients with a high clinical probability of pulmonary embolism or deep vein thrombosis before obtaining all diagnostic results.
For pulmonary embolism, heparin is usually infused IV for 7 to 10 days. A loading dose of 75 to 100 ii./kg (usually 5000 u.) is given as a bolus, followed by a continuous infusion of 15 u./kg/h, with a range of 10 to 30 u./kg/h. In the elderly, the usual initial infusion rate is 800 to 1000 u./h. The partial thromboplastin time should be checked 4 to 6 h after beginning therapy, and the infusion rate should be adjusted to achieve a value of 1.5 times the control. For the first 24 to 48 h. elderly patients have a standard response to heparin therapy. Subsequently, their partial thromboplastin lime may become abnormally elevated, requiring a decrease in the infusion rale, often by 25% or more. Heparin can also be infused intermittently, although ihe risk of bleeding is believed to be reduced by continuous administration. Adjusting the dose lo maintain Ihe partial thromboplastin lime at 1.5 times the control value reduces the risk of bleeding.
The major complications of heparin therapy are reversible thrombocytopenia and bleeding. Risk factors for bleeding during therapy include uremia, liver disease, surgery in the previous 2 wk. Gl bleeding in Ihe previous 6 mo. diastolic blood pressure > 110 mm Hg. and age > 60 yr. The risk of bleeding during therapy appears particularly high in women > 60 yr. About 5% to 15% of patients who receive heparin therapy require blood transfusion because of bleeding.
If maior bleeding occurs, the usual approach is to stop administering heparin and allow Ihe anticoagulant effect to dissipate over a few hours. Blood transfusions do not correct the anticoagulant cITccl of heparin. Protamine can inactivate heparin but generally is not used because of the risk of acute hypotension, dyspnea, and bradycardia.
Heparin can also be administered subcutaneously. Low-dose heparin, 5000 Li. s.c. bid. reduces the incidence of deep venous thrombosis, pulmonary embolism, and dealh from pulmonary embolism in patients undergoing abdominal surgery. Subcutaneous heparin is also used to prevent deep venous thrombosis in medical patients who are at risk of Ihrombosis—for example, bedridden patients and those who have severe heart failure, hemiparesis after a stroke, or a history of venous thrombosis.
Long-term anticoagulation is usually started in the hospital and continued after discharge using warfarin. With elderly patients, some physicians wait 24 lo 48 h after starting heparin lo begin warfarin. However, clinical studies indicate that warfarin therapy can safely begin al the same time as heparin therapy and that starting them at the same time substantially decreases the length and cost of hospital stay. Although warfarin administration for only 24 h may increase the prothrombin time, 3 to 7 days of therapy (5 to 10 mg daily) are generally needed to achieve a stable antithrombic state. For persons who cannot tolerate warfarin, heparin s.c, usually 10,000 u. q 12 h, may be given. Heparin should be continued for al leasl 3 days after the prothrombin time has become therapeutic.
How long anticoagulation should continue is unclear. In a patient with a temporary predisposing factor who has not had a previous clot, therapy is usually continued for 4 to 8 wk. In a patient who has had previous episodes of Ihrombosis, anticoagulant therapy is often given for 3 to 6 mo or continued indefinitely. The need for ongoing warfarin therapy should be reassessed periodically because such therapy poses at least a 10% risk of serious bleeding in the elderly.
Thrombolytic therapy should be considered for patients with deep venous thrombosis involving the iliofemoral system and for patients with massive pulmonary embolism who have significant pulmonary hypertension, obstruction of multiple segments of the pulmonary circulation, or systemic hypotension. Thrombolytic therapy is used in patients with severe proximal deep venous thrombosis because it can achieve greater revascularization of the deep veins in the leg than can heparin therapy.
Clot lysis may reduce the incidence of recurrent thrombi and post-phlebitic syndrome. A controlled clinical I rial indicated lhal thrombolytic therapy causes a faster relurn lo normal pulmonary arterial pressure than hcpiirin therapy docs. Thrombolytic therapy also relieves strain on the right side of the heart more quickly than heparin does. However, thrombolytic therapy does not improve survival. The potential benefits of this therapy have to be weighed against the greater possibility of hemorrhage, including an approximately 1% to 2%’ risk of intracranial bleeding. Thrombolytic therapy for deep venous thrombosis or pulmonary emboli has not been compared with heparin therapy in the elderly.
Streptokinase is the most commonly used thrombolytic agent, although urokinase is also effective and may be used in patients who are allergic or resistant to streptokinase. Tissue plasminogen activators are also useful: however, they offer no advantage over the thrombolytics while costing more. Streptokinase is administered initially as a rapid infusion (bolus) IV of 250,000 u. over 30 min. followed by a continuous infusion of 100,000 u./h for 1 to 3 days. The bolus neutralizes antistreptococeal antibody from previous streptococcal infections. Thrombolytic therapy is generally monitored by measuring thrombin time before therapy, 4 h after therapy begins, and then every 12 h. The objective is to increase the thrombin time to two to four times the base-line value.
After I to 3 days of streptokinase therapy, heparin is typically infused at the standard dose for 5 to 7 days. The heparin therapy should be started without a loading dose 4 h after discontinuing the streptokinase.
If major bleeding occurs, whole blood or fresh frozen plasma reverses the effect of streptokinase or urokinase.
Contraindications to thrombolytic therapy include eye or central nervous system surgery within the preceding 2 wk, intracranial neoplasms or vascular abnormalities, stroke within the preceding 2 mo, active bleeding, severe hypertension, and allergy to thrombolytic agents. Age alone is not known to be a contraindication, but experience with thrombolytic therapy in the elderly is limited.
Interruption of the inferior vena cava may be required in a small number of patients who have a contraindication to anticoagulation, fail to respond to anticoagulant therapy as demonstrated by recurrent emboli, or have pulmonary emboli from septic thrombophlebitis. The most common technique is to place a filter in the inferior vena cava. The filter is introduced percutaneously into the .jugular vein, then advanced to a position below the level of the renal veins. This procedure eliminates the immediale risk of further embolization from a clot in the legs. However; the immediate benefit must be balanced against possible complications, including chronic leg edema, thrombosis formation above the filter, recurrent embolization through collateral veins, perforation of the vena cava, and migration of the filter.
Endarterectomy may be helpful in patients who have chronic pulmonary hyperlension because of a clot occluding the main or lobar pulmonary arteries.