Symptoms and Signs
Presenting signs and symptoms for pulmonary embolism are nonspecific, which makes clinical diagnosis difficult. The most common presenting symptoms noted in the patients from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study who had angiographically confirmed PE were dyspnea, pleuritic chest pain, and tachypnea. The findings on physical examination included increased respiratory rate, rales, tachycardia, a loud second heart sound, deep venous thrombosis, temperature above 38.5°C, wheeze, Homan's sign (pain on palpation of the calf), pleural friction rub, an S3 gallop, and cyanosis. Syncope or hypotension may uncommonly be the presenting symptoms of pulmonary embolism and suggests severe hemodynamic compromise. The presence of the above clinical findings can heighten concern for PE but does not constitute a diagnosis.
Although clinical symptoms and signs are nonspecific, clinical models using findings from history and physical examination help focus clinical suspicion for PE. Recent clinical models use weighted clinical scores to assign low, moderate, or high clinical probability of a PE. Some use clinic assessment plus a noninvasive diagnostic test, such as the d-dimer assay that measures active fibrinolysis. Wells reports an example of such a score for DVT tested prospectively on a large number of patients. This model, which includes nine findings from history and physical examination, weighs these features into a clinical score of low, moderate, or high likelihood of DVT. The features included are leg swelling, pain to palpation, heart rate greater than 100 beats/min, immobilization, surgery in the previous 4 weeks, prior PE or DVT, hemoptysis, malignancy, and likelihood of PE greater than likelihood of other diagnoses. A low probability clinical score coupled with a negative d-dimer assay gave a negative predictive value of 99.5% (CI 99.1–100%) for PE. Clinical tools such as this combined clinical/laboratory assessment protocol are useful in stratifying information obtained from the history and physical examination to decide on further diagnostic testing.
Arterial Blood Gas (ABG)
ABG is of limited use in assessment of pulmonary embolism. Although respiratory alkalosis and hypoxemia are common findings, they should not be used in isolation to detect PE. In the prospective PIOPED trial, 8–23% of patients with PE confirmed by angiography had normal alveolar–arterial (A–a) oxygen gradients and 7% had completely normal ABG results. Although ABG findings should not be used to confirm a diagnosis of PE, profound hypoxemia without clear explanation should raise suspicion for possible PE.
D-dimer, a product of the fibrinolytic degradation of cross-linked fibrin, has emerged as a potentially useful serological marker in the assessment of PE. Its current use is to rule out pulmonary embolism in the appropriate clinical setting; sensitivity rates are in the mid-90% range. Fibrinolytic markers including d-dimer are, however, elevated in many other medical disorders including cancer, hepatic and renal insufficiency, septicemia, stroke, and major trauma, thus limiting specificity in these situations. Five methods have been developed for detecting elevations in d-dimer: (1) enzyme-linked immunosorbent assay (ELISA) testing, which has the highest sensitivity but low specificity, (2) latex agglutination testing, which has improved specificity but lower sensitivity, (3) the immunofiltration assay, (4) an immunoturbidometric assay, and, more recently, (5) the SimpliRED d-dimer agglutination assay, which uses a biospecific antibody directed against d-dimers and red blood cells. ELISA appears to have a high negative predictive value (91–100%) but is limited by longer testing time and lack of widespread availability. Latex agglutination testing is more readily available and requires less time, but is limited by a negative predictive value between 67 and 97%. To interpret these studies, it is important to know which test is used by the local clinical laboratory. Currently, although a negative d-dimer may be used to prevent further testing in the setting of low pretest probability and low probability imaging, it does not provide full assurance of the absence of a PE.
Findings on chest x-ray are rarely diagnostic for pulmonary embolism. Radiographs may often look completely normal. When abnormal, radiographs show infiltrates, pleural effusion, or atelectasis. Less common abnormalities include unilateral enlargement of a pulmonary artery, and the Westermark sign, which is the asymmetry of lung markings due to absence of perfusion distal to a clot; the hemithorax without the thrombus appears denser. Hampton's hump describes a pleural-based wedge-shaped infiltrate/atelectasis from an infarct. Chest radiography is most useful in diagnosing other processes that may present with a similar clinical picture such as pneumonia or pneumothorax. Often, the presence of a chest film showing little abnormality for a patient with new onset hypoxemia is a clue to the presence of pulmonary vascular disease such as PE.
The ventilation-perfusion scan (/Q) has been the most common diagnostic test for suspected pulmonary embolism. 99Tc-radiolabeled albumin is injected intravenously into the pulmonary capillary bed followed by inhalation of a radioactive gas to assess ventilation. A diagnosis of pulmonary embolism is based on the pattern of ventilatory and perfusion defects with PE causing large segmental decrease in perfusion with preserved ventilation. Major disadvantages of this test are the limitations posed by the presence of comorbid lung disease and the test's lack of sensitivity for small clots. These result in underdiagnosis of PE. Therefore nondiagnostic or negative /Q scanning must be considered in each clinical risk setting: high, moderate, or low likelihood of PE. PIOPED data have indicated that ventilation–perfusion scanning has a high positive predictive value (96%) in the setting of a high pretest clinical suspicion and a high probability scan (Figure 19–1). However, a low probability scan with the same high clinical suspicion still has an associated 40% incidence of pulmonary embolism (Table 19–2). Scans appear to be of particular use when they are either normal or high probability rather than low or indeterminant probability; in PIOPED the majority (75%) were nondiagnostic.
Commonly, physicians need to choose a diagnostic test for pulmonary embolism for a patient with significant pulmonary disease such as chronic obstructive pulmonary disease (COPD). Data suggest that the positive predictive value of /Q scanning remains the same, but that the incidence of indeterminant scans is much higher among those with COPD due to underlying ventilation abnormalities. In the setting of a nondiagnostic study, examination of lower extremity for thrombus may be used to assist in reaching a diagnosis.
Lower Extremity Doppler
Because pulmonary thromboemboli originate primarily in the legs, lower extremity (LE) Doppler and ultrasound studies are an alternative strategy for diagnosing suspected venous thromboembolic events, particularly in the setting of nondiagnostic /Q scans. Venous ultrasonography is a noninvasive and relatively inexpensive test that is useful in identifying proximal venous thrombosis. Doppler examination entails placement of an external probe for flow assessment. Patients with negative LE Dopplers and nondiagnostic /Q scan may be followed with serial Doppler/ultrasound examinations. Other modalities used to examine the lower extremities include impedance plethysmography and contrast venography. Lower extremity imaging, especially if positive for clot, may complement other diagnostic tests, especially indeterminate /Q scanning, even without direct visualization of the lung circulation.
Pulmonary angiography remains the gold standard for the diagnosis of pulmonary embolism. Diagnosis is based on pulmonary artery occlusion or the presence of intraluminal filling defects in two views. Other suggestive findings include asymmetrical blood flow, slow filling of the artery, and arterial cutoff. Pulmonary angiography is invasive; access is achieved via the femoral, basilic, or internal jugular vein. Angiography is reserved for a setting of high clinical suspicion when nondiagnostic testing is provided by the less invasive studies, since it has a higher complication rate due to the dye load and need for central vein catheter placement. It is important to recognize risks of angiography including bleeding risk and dye-induced nephropathy. Death has been reported in 0.2–0.5% of studies. Complications include arrhythmias and groin hematomas. Even high-risk patients, though, can safely undergo angiography if the platelet count is at least 75,000 L, coagulation studies are only minimally elevated, and adequate prestudy hydration is provided.
Helical Computed Tomography (CT) Scan
Recently, helical or spiral CT scanning has received attention as a primary diagnostic tool for acute pulmonary embolism. Helical CT scanning constructs a two-dimensional lung image over a brief period of time after injection of contrast dye. Defects in dye penetration of a vessel diagnostic of thrombus may be detected centrally or peripherally (Figure 19–2). Helical CT scanning has the advantage of being minimally invasive, similar to /Q scanning. To date, there is no consensus on the role of helical CT scanning in the diagnosis of acute PE. Prospective studies have reported sensitivities of 53–100% and specificities ranging from 81 to 100%. There are data in selected case series revealing a low incidence of PE among patients up to 3 months after a negative helical CT scan. However, studies have been limited by several features including small sample size, bias in patient selection, retrospective selection, presence or absence of comorbid conditions, and lack of angiography as the reference standard. Interobserver variation among radiologists remains a potential problem in scan interpretation. Although helical CT is effective in imaging main, lobar, and subsegmental emboli, it generally lacks resolution for detecting subsegmental (small) emboli. Some believe that it should be a first-line replacement for /Q scans and angiography, while others have suggested reserving it for selected patients in whom /Q scanning is nondiagnostic or unavailable. Currently, CT scanning appears useful in identifying central emboli, an area of weakness for /Q scans. It also identifies previously undetected parenchymal, pleural, and mediastinal abnormalities that could be alternate explanations for patient symptoms. A large multicenter trial is under way nationwide to assess the role of CT scanning prospectively. A promising extension of CT scanning is scanning of the pelvic and leg veins during the same injection protocol as CT of the chest to identify vena caval, iliac, or femoral venous thrombosis.
Magnetic Resonance Angiography
Magnetic resonance angiography (MRA) is an alternative method for diagnosing pulmonary vascular disease. To date, only small studies have examined the role of MRA in the diagnosis of acute PE with reports of sensitivities as high as 86% in main arteries and as low as 50% in lobar arteries. Earlier reports were limited technically by lack of contrast enhancement. Current studies using contrast-enhanced methods report slightly better results for this unproven test.
ECGs are of limited use in diagnosing acute PE. Most commonly, patients present with sinus tachycardia. Although patterns of right ventricular strain may be evident, these are often absent, especially for small emboli. Findings of right ventricular strain include right bundle branch block (RBBB), incomplete RBBB, T wave inversions in V1–V4 or III, S wave in I, Q wave in III, and S1Q3T3 complexes. In a prospective assessment of ECGs in patients with suspected pulmonary embolism, only sinus tachycardia [positive predictive value (PPV) 38%, negative predictive value (NPV) 81%] and incomplete RBBB (PPV 100%, NPV 77%) were significantly more frequent in patients with confirmed PE.
For the majority of patients, echocardiography adds little to diagnosis or treatment. In submassive PE, however, right ventricular electrocardiographic strain patterns vary with the severity of the pulmonary artery pressure estimated by echocardiogram. These patterns help estimate the extent of PE in clinically severe cases. Some authors have suggested that echocardiogram may identify right ventricular dysfunction in the suspected massive pulmonary embolism and guide a decision for use of thrombolytic therapy.
At present, there is no perfect algorithm for PE assessment. Experts have endorsed strategies such as the one outlined in Figure 19–3. Helical CT scans are playing an increasing role in diagnosis despite the lack of wide-based prospective testing. Their current use should probably be similar to the /Q scan with pursuance of low probability or negative results using a pulmonary angiogram as clinically indicated. Negative d-dimer assays may be added to a clinical algorithm to minimize further scanning in the low likelihood clinical settings.