Pulmonary Embolism
By Donald R. Elton, MD, FCCP
Lexington Pulmonary and Critical Care
Introduction
Pulmonary embolus is a common condition occurring in about 1 in 50 hospital admissions. Because of difficulties in positively ruling the diagnosis in or out, many physicians hesitate the raise the possibility that a pulmonary embolus may be present in a particular case though the mortality of an untreated pulmonary embolus may approach 30%.
Pathophysiology
95% of pulmonary emboli originate as lower extremity deep venous thrombi. A recent study demonstrated that about 50% of patients with DVT could be shown to have an unmatched perfusion defect by V/Q scan and of these 66% of these defects resolved after anticoagulation suggesting that these were acute pulmonary emboli. 10% of pulmonary emboli result in some degree of pulmonary infarction. It is not clear whether pulmonary embolic mortality is strictly related to pulmonary vascular obstruction (i.e. hemodynamic effects) or whether humoral or gas-exchange factors predominate. It would not be surprising if the dominate pathology varied among patients. Note that since normal patients are able to at least double their cardiac output (and thus their pulmonary blood flow) without significantly elevating their pulmonary artery pressure, that at least 50% of the pulmonary circulation would need to be obstructed by a pulmonary embolus before significant hemodynamic compromise resulting from mechanical obstruction would occur. This, of course, assumes that the pulmonary circulation is normal before the embolus occurs. Pulmonary embolic disease converts normal lung units into dead space units. This results in V/Q mismatches (i.e. areas of normal ventilation with reduced perfusion). This alteration in V/Q mismatching result in hypoxemia and results in a need for an increased minute volume to maintain the same PaCO2 level. If the mismatch is significant one would expect tachypnea and hypoxia to develop as a result of this mismatch.
Signs/Symptoms
Most symptoms of pulmonary embolus emanate directly from the pathophysiology. Some (hypoxia) relate from the creation of deadspace while others (right atrial enlargement on the EKG) result from increased pulmonary artery pressure from mechanical obstructive phenomena. Common findings in pulmonary embolus include:
hypoxia and respiratory alkalosis
EKG evidence of RV overload such as right ventricular hypertrophy or right atrial enlargement.
Increased deadspace as shown by Vd/Vt measurement (rarely measured).
Pleural effusion, frequently bloody.
Hypoperfusion on chest radiograph.
Unmatched perfusion defects on V/Q scan.
Positive pulmonary angiogram (gold standard).
Tachycardia (this is frequently the only objective finding).
Chest pain and dyspnea (very common).
Diagnostic Work-up
Once the possibility of pulmonary embolus has been raised, a diagnostic work-up must be conducted to either confirm or deny the diagnosis. Given the high rate of pulmonary embolus in patients with deep venous thrombosis, it could be argued that all patients with DVT should be worked up for PE as well. In most cases, the treatment for DVT will be the same as the treatment for PE therefore diagnosis of either will result in treatment though it would be useful in future management to know whether PE has occurred. The two main methods used to evaluate for PE are V/Q lung scanning and pulmonary arteriography. The pulmonary angiogram is the 'gold standard' for diagnosing or ruling out a pulmonary embolus. The risks are the risks of a central venous line plus the risk of IV contrast. The usual algorithm though is to start with a V/Q scan except in cases where the V/Q is non-diagnostic (this is frequent) or in cases where one would expect the V/Q scan to be difficult to interpret. The V/Q scan is really two tests, one to evaluate ventilation and one to evaluate perfusion. The ventilation test involves the patient breathing a radioactive tracer gas and sitting under the gamma camera to evaluate whether ventilation is normal in areas of the lung that may be shown to have abnormal perfusion on a perfusion scan. A high probability V/Q scan would be one that showed a segmental defect in perfusion without a matching defect in ventilation. V/Q scans in patients with significant ventilation defects are difficult to interpret and even in a low probability scan, the incidence of pulmonary embolus may be as high as 25%. A recent study demonstrated that V/Q scanning had a sensitivity of 98% with a specificity of only 10% if one considers low probability scans to be positive scans. If you decide that only high probability scans are positive then the sensitivity drops to 41% with a specificity of 97%. Because of this diagnostic uncertainty in ruling out PE (i.e. low sensitivity), a V/Q scan really needs to be very normal, not just low probability, to avoid doing a pulmonary arteriogram to rule out PE if clinical suspicion is high unless the plan is to just treat the patient emperically. If a V/Q scan is positive, however, treatment can begin. A recent studies (Hull) suggest that the combination of clinical suspicion (prior probability) and the V/Q scan agreeing with that clinical suspicion would be 95% sensitive and 95% specific. Unfortunately the basis of this estimate of clinical suspicion was not standardized or defined in the paper. Since 95% of pulmonary emboli originate from the legs, a venogram or venous doppler study can be used to detect the DVT and treatment can proceed if this is positive even though there is a possibility of a PE without a DVT (5%) and you could have a DVT without PE (around 50% of the time). The need for further work-up for PE in the patient with a DVT would depend on how seriously ill the patient was and whether further therapy specific for the PE was considered (i.e. thrombolytic therapy or embolectomy). The echocardiogram is frequently useful in evaluating the patient with suspected pulmonary embolus. In some cases residual clot can be imaged in the right ventricle or right atrium (a finding that suggests a high likelihood of another embolus soon) and right ventricular overload can be demonstrated if it is present.
Chemical Tests for PE
Recently there has been work done to try to develop assays for serum and urine markers of pulmonary embolic disease. So far, these tests have a fairly high degree of sensitivity but have a fairly low specificity which means that they can be used to rule out a pulmonary embolus but they cannot be used to confirm one. This is still very useful, however, as they tests can be used as evidence to avoid an expensive, and perhaps risky, work up in patients who fail to show the markers. One test, the D-dimer test, measures the level of a product of fibrin degradation. A serum D-dimer concentration of less than 500 ug/l has a negative predictive value of 98% meaning that less than 2% of persons with a D-dimer level below 500 will be later found to have a pulmonary embolus. The sensitivity of this test remained high even 3 and 7 days after presentation. The RMH laboratory (1991) provides the D-dimer test on demand for a cost of $42 (a CBC is $48) and a testing time of under one hour. A recent paper (Leitha et al) has cast some controversy on the utility of the D-dimer test showing a sensitivity closer to 50% for predicting a high-probability V/Q scan if 500 ng/ml is the cut-off and 84% if the cut-off is 120 ng/ml. It should be noted, however, that V/Q scans may remain abnormal for some time (perhaps months or longer in some cases) after an acute event so a study using a V/Q scan as the end-point might not be valid as a test of the accuracy of the D-dimer study as a screening test for pulmonary embolus. In any case, realized that this use of the D-dimer study is likely to be the subject of further study before its utility is generally accepted. There is more than one methodology of D-Dimer test in common use in laboratories. Only the quantitative measurement techniques are really sensitive enough to be of much utility in ruling out a PE.
Treatment
Most pulmonary emboli are treated with systemic anti-coagulation. This means IV heparin followed by coumadin. Note the table below on how to actually administer these drugs. There have been some trials of thrombolytic therapy and thus far the results are promising but it remains to be seen whether morbidity and mortality are improved by this therapy. Thrombolysis is probably indicated for patients with hemodynamic compromise from a pulmonary embolus in the absense of contraindications and will possibly gain acceptance as treatment for all symptomatic emoboli in the future. Embolectomy is a therapy of last resort and most patients who might benefit from it are very sick and many die before the diagnosis is even certain.
References
Hyers TM, Hull RD, Weg JG: Antithrombotic Therapy for Venous Thromboembolic Disease, Chest 95:2, February 1989 supplement.
The PIOPED investigators: Value of Ventilation/Perfusion Scan in Acute Pulmonary Embolism, Results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED), JAMA 263:20, May 1990.
Bone RC: Ventilation/Perfusion Scan in Pulmonary Embolism, 'The Emperor is Incompletely Attired', JAMA 1990; 263:20.
Bell WR: The Clinical Features of Submassive and Massive Pulmonary Emboli, AM J MED 1977; Vol. 62.
Hull RD: Diagnostic Value of Ventilation-Perfusion Lung Scanning in Patients with Suspected Pulmonary Embolism, Chest 1991; 88:6.
Tulchinsky, M, Zeller JA, Reba RC: Urinary Fibrinopeptide A in Evaluation of Patients with Suspected Acute Pulmonary Embolism, Chest 1991; 100:394-98.
Bounameaux H, Cirafici P, De Moerloose P, et al: Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism, Lancet 1991; 337:196-200.
Kelly MA, Carson JL, Palevsky HI, Schwartz JS: Diagnosing Pulmonary Embolism: New Facts and Strategies, Annals of Internal Medicine 1991; 114: 300-306.
Hull RD, Hirsch J, Carter CJ, et al: Diagnostic value of ventilation-perfusion lung scanning in patients with suspected pulmonary embolism, Chest 1985; 88: 819-28.
Hull RD, Hirsh J, Carter CJ, et al: Pulmonary angiography, ventilation lung scanning, and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan, Ann Intern Med 1983; 98: 891-9.
Leitha T, Speiser W, Dudczak R: Pulmonary Embolism, Efficacy of D-dimer and thrombin-antithrombin III complex determinations as screening tests before lung scanning, Chest 1991; 100:1536-41.