P. M. M. Kuijer

Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism

The clinical diagnosis of pulmonary embolism is an insufficient basis for initiating long-term anticoagulant therapy [1, 2]. When objective tests are used, the diagnosis of pulmonary embolus is confirmed in only about 30% of patients in whom the condition is suspected [1, 2]. It is important to identify patients with pulmonary embolism because adequate anticoagulant treatment reduces morbidity and mortality from recurrent thromboembolic disease [3]. However, anticoagulant therapy carries a substantial risk for major bleeding [4]. Thus, it is equally important to identify patients without pulmonary embolism from whom anticoagulant therapy can be safely withheld. Lung scintigraphy remains the test of first choice for the diagnostic work-up of patients suspected of having pulmonary embolism. It has been conclusively shown that anticoagulant agents can be safely withheld from patients who have normal scans [5, 6]. In patients with segmental or larger perfusion defects and locally normal ventilation (that is, patients with high-probability lung scans), the diagnosis is sufficiently proven to warrant long-term anticoagulant therapy [1, 2, 7]. Unfortunately, the lung scan is neither normal nor high-probability in 40% to 60% of patients [1, 2, 7-9]. Further investigation is required because the prevalence of pulmonary embolism in this group is still approximately 20% to 40% [1, 2, 9, 10]. Pulmonary angiography is generally considered the definitive test, but this method is invasive and requires substantial technical resources and expertise for proper execution [9, 11]. Therefore, several alternate noninvasive methods that reduce the need for pulmonary angiography have been advocated; these include tests for the measurement of coagulation activation [12, 13], clinical decision rules [14, 15], and spiral computed tomography [16]. On the basis of the concept that pulmonary embolism and deep venous thrombosis are manifestations of the same disease, some investigators have evaluated the use of tests for the detection of venous thrombosis of the leg in the diagnostic work-up of patients suspected of having pulmonary embolism [17, 18]. To be clinically useful, such a test should be simple, readily available, and highly accurate. Compression ultrasonography has been shown to be reliable for detecting and excluding thrombosis in patients in whom deep venous thrombosis is clinically suspected [19-21]. However, in nonsymptomatic persons with a high risk for thrombosis (for example, patients who have recently undergone hip surgery), this test did not prove clinically useful, primarily because of an insufficient sensitivity [22-24]. We sought to determine the diagnostic value of compression ultrasonography in consecutive patients suspected of having pulmonary embolism. We then used our findings to assess the potential contribution of compression ultrasonography to the diagnostic management of symptomatic patients. Methods Patients Patients were eligible for the study if they were 18 years of age or older and underwent perfusion-ventilation lung scanning for a diagnostic work-up of pulmonary embolism at the Academic Medical Center in Amsterdam, the Netherlands. All patients were primarily referred because pulmonary embolism was clinically suspected (outpatients) or because they developed signs or symptoms of pulmonary embolism during hospitalization for another illness (inpatients). All patients were scheduled to undergo ultrasonography as soon as possible; this test was done independently of the other tests. All patients were prospectively followed for 6 months. The study protocol was approved by the institutional review board, and informed consent was obtained for all patients. Diagnostic Methods Perfusion lung scanning was done in all patients after the administration of 100 MBq of 99mTechnetium-labeled macroaggregates of albumin. Six views were routinely obtained: anterior, posterior, left and right lateral, and left and right posterior oblique. Lung scans were interpreted by using an anatomic-segment lung chart [25] and were considered normal if no perfusion defects were seen in any of the six projections. If segmental or larger defects were seen, ventilation lung scanning was done using 81mKrypton gas. Pulmonary embolism was considered to be excluded if the lung scan was normal and was considered to be proven if a high-probability scan (that is, a scan showing at least one segmental perfusion defect with locally normal ventilation [1, 7]) was obtained. Selective pulmonary angiography was attempted in all patients who had a nondiagnostic lung scan. Angiography involved a modified Seldinger approach with a 6.7F-braded, multiple side-holed, Grollman-type pig-tail catheter. The angiogram was classified according to standard definitions as normal, indicative of pulmonary embolism, or inadequate for interpretation [1, 2, 9]. B-mode gray-scale compression ultrasonography was done with a 7.5-MHz linear-array sonographic scanner. While the patient was in the supine position, the common femoral vein was visualized at the inguinal ligament; the adjacent artery was used as a reference point. The popliteal vein was scanned while the patient was in the prone or lateral decubitus position, and the transducer was placed posteriorly in the mid-popliteal fossa. For evaluation of the distal popliteal vein, the transducer was moved slowly from the popliteal fossa along the calf until the trifurcation of the calf veins was visualized. No attempt was made to visualize the calf veins. Ultrasonographic results were considered abnormal (that is, consistent with the presence of deep venous thrombosis) if a venous segment could not be completely compressed [19-21]. All patients underwent bilateral compression ultrasonography, which was done by an independent investigator who was not aware of the results of lung scanning or pulmonary angiography. Results of compression ultrasonography were not forwarded to the referring physician, and decisions about anticoagulant treatment were based on the results of lung scanning or pulmonary angiography. Statistical Analysis The rate of abnormal compression ultrasonography in patients in whom pulmonary embolism was proven (sensitivity) was calculated for all patients and for patients with the diagnosis of pulmonary embolism by using as a conjoint gold standard a high-probability lung scan or a non-high-probability lung scan plus a subsequent abnormal angiogram. We also determined the rate of abnormal ultrasonographic results in patients in whom pulmonary embolism was excluded by either a normal lung scan or a normal angiogram (1 specificity). Finally, the rate of abnormal results on compression ultrasonography was calculated for patients whose diagnosis of pulmonary embolism was uncertain because angiography could not be performed or because the result could not be interpreted. The possible contribution of compression ultrasonography to the diagnostic management of symptomatic patients was assessed by 1) calculating the number of lung scans and angiograms that could be avoided if compression ultrasonography yielded abnormal results and 2) determining the number of patients who would be inappropriately treated with anticoagulation because of false-positive ultrasonographic results. These calculations were done by applying the sensitivity and specificity of compression ultrasonography obtained in our study to a hypothetical population of 1000 patients suspected of having pulmonary embolism; the proportional distribution of lung scanning and angiography results were the same as those seen in our study. To minimize bias, all 397 patients (including the 40 patients in whom ultrasonography was not done) were used to calculate the necessary figures. We assumed that the prevalence of pulmonary embolism in the 30 patients without a diagnosis (those whose lung scan was nondiagnostic but who did not undergo pulmonary angiography) was 27%, as was seen in the remaining patients who had a nondiagnostic lung scan. Furthermore, the sensitivity and specificity of ultrasonography in these 30 patients were assumed to be similar to those obtained in the cohort of patients with a nondiagnostic lung scan in whom angiography was done. This resulted in an overall calculated prevalence of pulmonary embolism of 41.1%, with a high-probability lung scan in 30.2% of these patients and a nondiagnostic lung scan in 40.6%. Pulmonary embolism was considered to be present in 27% of patients who had a nondiagnostic lung scan (if angiography had been performed). Finally, we assumed that all patients with abnormal ultrasonographic results would be treated with anticoagulant agents without further testing. Results A total of 397 consecutive patients who were clinically suspected of having pulmonary embolism were enrolled (Figure 1). The mean age was 56 years (range, 18 to 92 years); 223 patients (56%) were women, and 206 (52%) were outpatients. Twenty-four percent of patients had cancer, 21% had recently had surgery, 12% had congestive heart failure, and 12% had a history of venous thromboembolism. No risk factor was seen in 26% of patients. The median interval between the onset of symptoms and diagnostic investigations was 2 days. Compression ultrasonography could not be done in 40 patients. Thirty of these patients had a normal perfusion lung scan; 22 of the 30 were outpatients for whom compression ultrasonography could not be arranged before they left. Compression ultrasonography was not performed in 4 patients who had a high-probability lung scan and 6 patients who had a nondiagnostic lung scan (angiography results were abnormal in 1 patient and normal in 2; angiography was not done in 3 patients). Treatment decisions in these 40 patients were made on the basis of lung scans and angiography results, as was done for the 357 patients in whom ultrasonography was performed. Figure 1. Flow diagram of test outcomes of 397 patients suspected of having pul

The clinical course of patients with suspected pulmonary embolism.

BACKGROUND The outcome of patients with suspected pulmonary embolism is known to a limited extent only. OBJECTIVE To address this limited knowledge in a cohort in whom pulmonary embolism was proved or ruled out. METHODS Consecutive patients with clinically suspected pulmonary embolism underwent lung scintigraphy and angiography if required. Pulmonary embolism was excluded by normal results of a lung scan or angiogram, and, if so, anticoagulant therapy was withheld. Pulmonary embolism was proved with a high-probability perfusion-ventilation lung scan or a confirmatory angiogram if a nondiagnostic lung scan was obtained. These patients were treated with heparin intravenously and anticoagulants orally on a long-term basis. All patients were followed up for 6 months, with a special focus on recurrent thromboembolism, bleeding complications, and mortality. RESULTS A total of 487 consecutive inpatients and outpatients were included. Pulmonary embolism was excluded or proved in 243 and 193 patients, respectively. In 51 patients a definite diagnosis could not be established. The overall prevalence of pulmonary embolism was 39%. In patients in whom pulmonary embolism was proved, excluded, or uncertain, recurrent venous thromboembolism was observed in 2.6%, 0.9%, and 2%, respectively. Serious bleeding complications occurred in 7 patients (3.3%; 95% confidence interval [CI], 1.8%-6.3%), 2 cases of which were fatal. The total mortality after 6 months in patients with proved or excluded pulmonary embolism was 17% (95% CI, 12%-23%) and 11% (95% CI, 7%-15%), respectively. Death was related to (recurrent) pulmonary embolism in 5% and 0% of these cases, respectively. CONCLUSIONS During a 6-month period, recurrent pulmonary embolism occurred in approximately 5 patients (2.5%) who were treated for a previous episode. Fatal bleeding complications attributable to the use of anticoagulants were encountered in 1%. The mortality among patients with suspected pulmonary embolism was considerable. However, most deaths were unrelated to pulmonary embolism, but were the result of serious underlying illnesses.

A survey of the diagnostic and therapeutic management of patients with suspected pulmonary embolism in the Netherlands

BACKGROUND Pulmonary embolism (PE) remains a complex diagnostic problem. Many diagnostic modalities are available. Several published guidelines have failed to yield a uniform approach. We have assessed the current diagnostic and therapeutic management of patients with clinically suspected PE in the Netherlands. METHODS A questionnaire was sent to internists and pulmonologists, who were then asked to detail their diagnostic and therapeutic management in their last patient seen with suspected PE. RESULTS 1571 questionnaires were sent out (response rate 64%). 95% of the patients with suspected PE underwent a perfusion scan (in 91% within 24 h). 1.6% of the respondents had no available perfusion scan facility. Of those who underwent a perfusion scan, 62% had ventilation scan (66% with segmental defects, 80% with subsegmental defects, 27% with a normal perfusion scan). Tests for deep vein thrombosis were performed in 58% of the patients and pulmonary angiography was carried out in 6.1%. Anticoagulant treatment was instituted in 73.2% of all patients. CONCLUSIONS The perfusion lung scan is appropriately used as the initial step in the diagnostic workup of patients with suspected PE. Ventilation scanning is overused in patients with subsegmental perfusion defects and normal scan results, whereas it is underused in patients with segmental defects. Additional ventilation scan results had a limited influence on treatment decisions. There is still considerable overtreatment of patients with suspected PE.