Donald Armstrong, 71 years old, arrives at the emergency department after falling down the stairs at his home. He recalls feeling short of breath and light-headed before going downstairs, and he admits that he has felt short of breath since taking a four-hour airplane flight two weeks earlier. In the assessment, he is managed as if he were a trauma patient until the only injury found is a forehead laceration. The focus of the evaluation then shifts to the cause of the fall. The patient denies chest pain, cough, or fever, and his vital signs on admission are blood pressure, 126/80 mmHg; pulse, 96 beats per minute; respiration, 24 breaths per minute; temperature, 98.4°F; and oxygen saturation on room air, 89%, increasing to 94% on 100% FiO 2 provided by nonrebreathing mask. Examination reveals an edematous left lower leg and thigh with palpable pulses. Medical history includes recent upper gastrointestinal bleeding with three large gastric ulcers. Biopsies indicated the possibility of lymphoma. It is suspected that Mr. Armstrong has both deep venous thrombosis (DVT) and pulmonary embolism (PE), and he is scheduled for duplex ultrasound and a ventilation–perfusion (VQ) lung scan.
Acute PE, a pulmonary manifestation of a circulatory problem, is a serious condition caused by obstruction of blood flow in one or more pulmonary arteries (PA). Almost all PEs are caused by a thrombus, but they also can result from fat globules, air, amniotic fluid, septic clots, or tumor fragments. 1 PE occurs in at least 650,000 people each year in the United States and is either the first or second most common cause of unexpected natural death in most age groups. 1 Hospitalized patients are at highest risk, particularly the elderly. The diagnosis of PE is correctly made in only 10% of patients over 70 years of age. 1 In general, however, diagnosis is often missed in approximately 70% of cases and autopsy results show that up to 60% of deceased hospitalized patients have had a PE, a circumstance that has elicited to the condition the moniker “the great masquerader.”1,2 If left untreated, PE carries a 30% mortality rate. 1 In patients with concurrent cardiac disease or cancer, that rate is about 20%, even with treatment of PE. However, when patients with uncomplicated PE are rapidly identified and treated appropriately, mortality rate is 2.5%. 3
In 1856, Rudolf Virchow identified a triad of factors that predispose toward the development of intravascular thrombus: a hypercoagulable state, vessel wall injury, and venous stasis (see Risk factors for PE, page 19). The most important clinically identifiable risks for DVT and subsequent PE are a history of DVT or PE or both, recent surgery or pregnancy, prolonged immobilization, and underlying malignancy. 1
Hypercoagulable states may exist in asymptomatic patients, and may be either primary or secondary. Examples of primary hypercoagulability include clotting protein mutations that predispose the patient to develop thrombus. Factor V (Leiden) abnormality is the most common inherited risk for PE. 4 Secondary causes of hypercoagulability include pregnancy and the postpartum period, and PE is the most common cause of maternal death after a live birth. 5 Some malignant tumor cells secrete procoagulants that increase the risk of developing venous thrombi. Patients with nephrotic syndrome also are prone to hypercoagulable states. Trauma or surgery can produce a hypercoagulable state through activation of factor X.
Vessel wall injuries may occur during surgical procedures involving the stretching or torsion of vessels, with intimal tears providing a locus for platelet aggregation and clot formation. Intravascular catheterization or trauma can also injure vessel walls. Thrombus formation occurs often in bilateral lower extremities and is usually asymptomatic.
Venous stasis is a serious complication of immobility, especially if it persists longer than one week. Stasis allows the red blood cells, platelets, fibrin, and white blood cells to adhere to the vessel wall, usually around valves. Varicosities and obesity may enhance venous stasis as a result of venous valvular dysfunction. The clot enlarges in the direction of blood flow, advancing proximally into larger-caliber vessels. Twenty-five percent of calf vein thrombi extend into the deep veins of the thigh and pelvis, and 10% of these embolize. 6 Thrombi may fracture because of shear stress, trauma, changes in vascular pressure, muscle spasms, or thrombus dissolution. 7 When a thrombus breaks free from the vessel wall, it travels by way of the inferior vena cava to the right atrium (RA), through the right ventricle (RV), and into the PA until it enters a vessel too small to pass through. Blood flow is then obstructed to the distal lung tissue. The physiologic effects of PE depend on the amount and location of clotting, as well as on the preexisting cardiovascular and pulmonary functional status of the patient. Lung tissues have a dual blood supply from the pulmonary and bronchial arterial circulations, which offers some protection from pulmonary infarction. PEs are classified as either massive or submassive. A massive PE that obstructs 50% or more of segmental vasculature, or equivalent amount of clot in the proximal vasculature, can result in hypoxemia, increased RV afterload, and elevated PA systolic pressure. This creates a high risk of sudden death and chronic pulmonary hypertension. Submassive PE indicates an emboli in one or more pulmonary segments without RV or PA systolic pressure elevations. It imparts a lower risk of either early death or chronic pulmonary hypertension.
The blockage of a PA creates a VQ mismatch because ventilated alveoli are not being perfused. This results in increased dead space, decreased oxygen diffusing capacity, and hypoxemia. Obstruction of the alveolar arterial supply also results in regional loss of surfactant production, followed by alveolar collapse and atelectasis. 1 Minute ventilation increases are accompanied by decreased vital capacity from pain, splinting, atelectasis, and decreased lung compliance. Airway resistance rises in response to decreased PaCO 2 , as well as to serotonin, histamine, and kinin release.
Hypotension and decreased cardiac output (CO) occur in patients with a massive PE. An embolus clot in the PA obstructs RV outflow and causes the release of vasoconstrictive chemical mediators, leading to increased RV afterload. RV and RA filling pressures rise, causing RV dilatation. Tricuspid valvular dysfunction and regurgitation may occur because of incomplete valve closure in systole resulting from RV dilatation. The increased right heart pressure causes bulging of the interventricular septum into the left ventricle (LV), interfering with LV diastolic filling and end-diastolic volume. Decreased CO results from the loss of LV preload. Myocardial ischemia may follow because of decreased CO.
Patients with a PE present with a variety of vague complaints, making diagnosis difficult. The classic triad of signs and symptoms of PE (chest pain, dyspnea, and hemoptysis) are neither sensitive nor specific; they occur in fewer than 20% of patients in whom the diagnosis is made. 1 Reported Signs and Symptoms of Massive PE (at right) shows the relative incidence of reported signs and symptoms of PE in patients with a massive PE. 1
Small areas of infarcted tissue in the lung periphery may cause pleuritic chest pain. Thus, chest pain may be associated with even submassive PEs as they lodge in the smaller and more peripheral pulmonary arteries. Pain may be caused by leakage of blood from injured pulmonary capillary walls, with resultant pleural irritation. The spontaneous onset of chest wall tenderness without a history of trauma is reason to be concerned, and in some patients with PE chest wall tenderness is the only physical finding. 1
In Mr. Armstrong’s case, his presentation of dyspnea and hypoxia leading to a syncopal episode was initially overshadowed by his suspected injuries. He didn’t complain of chest pain in the ED.
PATIENT ASSESSMENT AND DIAGNOSTICS
Because of the nonspecific nature of patient complaints, clinical suspicion of PE should guide diagnostic testing. Clinicians integrate signs and symptoms, known risk factors, clinical assessments, chest X-ray, as well as laboratory and ECG results to form this clinical suspicion before performing more invasive diagnostic tests, such as VQ scans and pulmonary angiography. Many patients begin treatment for PE on the basis of history and the clinical examination, before definitive diagnostic testing has been completed. The key to timely diagnosis remains an accurate history and identifying risk factors for the development of a PE.
12-lead ECG. There’s no particular ECG abnormality found in all patients with significant PE. Obtaining a 12-lead ECG early can support a diagnosis of PE by ruling out acute myocardial infarction. 8 Tachycardia, unspecific ST and T-wave changes, tall peaked P waves in leads II, III, and aVF, and a right bundlebranch block are ECG changes that may be seen with PE. 8 Unless the patient has a massive PE, the ECG isn’t likely to be diagnostic. Hypoxemia, pulmonary hypertension, and acute right ventricular failure, also known as acute cor pulmonale, are caused by the critical obstruction of the PA system that occurs with a massive PE. 9 Pulseless electrical activity (PEA) may be the final cardiac presentation in this sequelae of events.
Echocardiogram. An echocardiogram is most effective when used in conjunction with the 12-lead ECG and it may be more easily performed in an unstable patient than a VQ scan is. Changes indicating increased pulmonary hemodynamics such as enlarged right-sided heart chambers, or tricuspid regurgitation may be seen. More than 75% of patients with PE have abnormalities of RV size, function, or tricuspid regurgitation. 8
Duplex ultrasound. Compression ultrasonography of the lower extremities may be useful in determining the source of emboli, but it’s of limited use in the emergency management of PE. In a patient presenting with a clinical evaluation consistent with PE, a negative ultrasound examination doesn’t rule out the diagnosis. 1 Many DVTs occur in areas that are inaccessible to ultrasonic examination, and in 66% of patients with PE, the site of DVT cannot be visualized this way. 1 It’s also possible for a patient to have significant venous thrombosis and a negative ultrasound examination because an entire thrombus can detach from the vessel wall and embolize in the lung.
Arterial blood gas (ABG) Analysis. Nearly 90% of patients with PE are found to have hypoxemia and hypocapnia on ABG analysis. 8 However, the absence of hypoxemia doesn’t rule out the diagnosis of PE, nor is its presence specific to PE. Normal ABG results may be seen either in the presence of a submassive PE or before the effects of occlusion are detectable. 8 The ABG should be used as an adjunct tool, the results of which should be reviewed in conjunction with those of other diagnostic tests.
Chest X-ray. The initial chest radiograph (CXR) of a patient with PE is almost always normal. 1 With time, as surfactant is destroyed, small areas of atelectasis or an infiltrate develop. 10 If PE is present in a large PA, this artery may be dilated proximal to the embolus with sudden constriction of the artery distally. If a pulmonary infarct has occurred, there may be “tenting” or a wedge-shaped infiltrate near the diaphragm and a pleural effusion. 10 In the emergency setting, CXRs are most useful in excluding other sources of the patient’s symptoms, such as pneumonia.
Ventilation–Perfusion Scan. Nuclear VQ lung scan is the single most important diagnostic procedure for PE available to the emergency clinician. 1 A VQ scan is indicated whenever the PE is suspected and no alternative diagnosis can be established. 1 The test compares the amount of perfusion in a lung segment with the degree of ventilation in that segment. 10 In the patient with PE, ventilation is normal but segmental perfusion is decreased or absent. VQ scans are classified as normal, high-probability, or nondiagnostic. 1 Ventilation–Perfusion Lung Scan Findings (page 23) provides more detail on the range of VQ scan findings. A normal lung scan rules out the diagnosis of PE in 98% of cases. 1 The combination of a clinical suspicion of PE with a high-probability scan accurately diagnoses PE in 96% of cases. 11 Nondiagnostic scans don’t rule out the presence of PE. This finding demonstrates the need for a thorough medical history of the patient, clinical assessment, and maintenance of a high degree of vigilance.
Angiography. Pulmonary arteriography is the gold standard in the diagnosis of PE. 10 It’s indicated in patients who have a high probability of having a PE and a nondiagnostic VQ scan. 10 When this test is performed carefully and completely, a positive pulmonary angiogram provides virtually 100% certainty that an obstruction to PA blood flow exists, whereas a negative result provides greater than 90% certainty that it does not. 1 Abnormal findings include abrupt arterial cutoffs and intraluminal filling defects. 10 The utility of this test in the emergency setting is limited by the risks associated with the procedure and the capability of facilities in performing it on an emergent basis.
OTHER LABORATORY DIAGNOSTICS
Plasma D-dimer. This is a unique product of the breakdown of cross-linked fibrin. It can be clinically detected in a serum assay (ELISA test) that is considered positive if the level is higher than 500 ng/mL. 1 Since D-dimer isn’t sensitive or specific enough to change the course of diagnostic evaluation or treatment of patients with suspected PE, the test result should be viewed as adjunctive to the clinical assessment.
The white blood cell (WBC) count may be either normal or elevated; it isn’t uncommon to see a WBC count as high as 20,000/mm 3 in patients with PE. Clotting studies are normal in most patients with PE. Prolonging the PT will not change the patient’s prognosis. Recurrent DVT and PE can occur in patients whose blood has been fully anticoagulated. 1
Mr. Armstrong’s duplex ultrasound scan revealed thrombi in the left common iliac to mid-superficial vein. The VQ scan was classified as high-probability and showed multiple bilateral pulmonary emboli.
The goals of treatment of acute PE include maintaining normal systemic perfusion and oxygenation, preventing further embolization, and restoring perfusion to affected lung segments. Oxygen must be administered to every patient with suspected PE, even when the arterial PO 2 is normal, because increased alveolar oxygen may help to promote pulmonary vascular dilatation. 1
Anticoagulation. Therapy directed toward the minimization of hypercoagulability includes anticoagulation with heparin and warfarin. Full-dose low-molecular-weight heparin (LMWH) or full-dose unfractionated intravenous heparin must be initiated at the time when DVT or PE is first suspected. 1 Anticoagulation prevents the formation of further clots but doesn’t dissolve the existing one. 1 The clot will be lysed by the body’s innate fibrinolytic mechanisms, which begin breaking down intraluminal clots within 24 hours and lyse 80% of thrombi within seven days. When clinical suspicion is high, patients must be heparinized while definitive diagnosis is awaited; effective anticoagulation reduces the mortality rate of PE from 30% to lower than 10%. 1 With proper dosing, several LMWH products have been found to be safe and effective in both prophylaxis and treatment of DVT and PE. 1 It isn’t necessary to monitor the aPTT of patients on LMWH, as LMWH does not significantly alter their aPTT values. 1
When intravenous heparin therapy is administered, adequate anticoagulation is indicated by an aPTT of 1.5 to two times the upper limit of normal range. This minimizes recurrent thromboembolic events without risk of bleeding. Clinicians must be aware of the 5% risk of serious bleeding in patients who are postoperative or who have suffered traumatic injuries, in those with peptic ulcer disease or occult malignancies, and in those who have liver disease or hemostatic defects. The desired aPTT level should be reached within the first 24 hours of onset of symptoms to decrease the risk of further thromboembolic events.
After anticoagulation with heparin, warfarin therapy is administered while continuing heparin for another four to six days. This concurrence prevents the patient from losing anticoagulation before adequate international normalized ratio (INR) levels are reached. Warfarin is unsafe for use in pregnant women, as it may cause fetal demise. The optimal total duration of anticoagulation is disputed; however, there’s a general consensus regarding significant reduction in recurrences and a net favorable benefit associated with at least six months of anticoagulation. 1
Fibrinolytics. Fibrinolytic therapy should be considered for every patient who has suffered any degree of hypotension or who is significantly hypoxemic from PE. 1 The presence of hypotension is an indication that the patient has exhausted cardiopulmonary reserves and is at high risk for sudden collapse and death. Over the past 20 years, many studies have consistently demonstrated that fibrinolytic therapy dramatically reduces the mortality, morbidity, and rate of recurrence of PE regardless of the size or type of PE at the time of presentation. 1 Early fibrinolytic therapy in the setting of PE is directed toward the resolution of pulmonary perfusion defects and the normalization of pulmonary hemodynamics.
Fibrinolytic agents activate circulating plasminogen, producing the proteolytic enzyme plasmin. Plasmin breaks down fibrin in thrombi, resulting in the dissolution of both obstructive clots in the pulmonary arteries as well as those in peripheral veins. Fibrinolytic agents work far more quickly than does the body’s inherent fibrinolytic system. The main risk in fibrinolysis is bleeding. A variety of fibrinolytic agents are available, including recombinant tissue plasminogen activator (tPA and rt-PA), streptokinase, and urokinase. 1 The faster-acting recombinant tissue plasminogen activators are preferred for the patient with PE because the condition can deteriorate rapidly. Administration methods are systemic or localized infusions, depending on the availability of catheterization laboratories and personnel.
Surgical intervention. Surgical pulmonary embolectomy is usually reserved for those patients with massive PE who are not candidates for receiving fibrinolytics, or for those in whom fibrinolytic therapy has failed to dissolve the PE. 1 The procedure is high-risk and is associated with a high mortality rate. The pulmonary artery is opened and the thrombus removed. Candidates for this procedure usually have suffered obstruction of more than 50% of pulmonary arteries and exhibit signs of cardiogenic shock.
Cardiac arrest therapy. Traditional advanced cardiac life support (ACLS) protocols are of little value in patients in whom cardiac arrest results from PE because obstruction of the pulmonary circuit prevents oxygenated blood from reaching the peripheral and cerebral circulation. The only management approaches likely to be helpful in this situation are emergency cardiopulmonary bypass or emergency thoracotomy. 1 Although experience with these procedures is limited, one study reports the complete recovery of seven patients out of nine in whom cardiopulmonary bypass was used to stabilize them for operative embolectomy. 1
Mr. Armstrong’s recent history of GI bleeding delayed his therapy for PE. He underwent emergency gastroscopy to rule out bleeding and was not considered a candidate for receiving fibrinolytics. He was heparinized and admitted to a medical unit. Less than 24 hours after admission, he suffered a cardiac arrest with pulseless electrical activity. Traditional ACLS protocols were not effective in restoring cardiopulmonary function. Neither cardiopulmonary bypass nor emergency thoracotomy procedures was attempted. Autopsy findings included bilateral PE occluding both the right and left main pulmonary arteries, as well as multifocal solid tumor masses involving 30% of the liver. It’s thought that Mr. Armstrong’s hypercoagulable state induced by the malignancy in combination with venous stasis resulting from immobility during his recent lengthy airplane flight may have accounted for the PE.
© 2001 Lippincott Williams & Wilkins, Inc.