E. J. R. Van Beek

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 Value of Radiographs and Bone Scintigraphy in Suspected Scaphoid Fracture A Statistical Analysis

The role of radiography and bone scintigraphy in the diagnostic management of suspected scaphoid fracture is controversial. Two strategies were compared for patients with initial negative radiographs: repeated radiography versus selective bone scintigraphy. Using the known positive predictive value of scintigraphy, the sensitivity and specificity of both diagnostic strategies were evaluated in a series of 78 consecutive patients. The kappa value for initial radiographs was 0.76 but decreased to 0.5 for follow-up radiographs. Similarly, sensitivity decreased from 64% to 30% in follow-up radiographs. Specificity of the bone scan was 98%. The best diagnostic strategy in the management of clinically suspected scaphoid fractures consists of initial radiography followed by bone scintigraphy in patients with negative radiographs.

Diagnosing scaphoid fractures radiographs cannot be used as a gold standard

To evaluate the reproducibility of the interpretation of radiographs for the diagnosis of scaphoid fractures, 134 radiographs (60 consecutive patients) were blindly observed by a resident radiologist, consultant radiologist, resident trauma surgeon and consultant trauma surgeon. The results of radiographs were analysed using kappa (kappa) statistics and stratified according to the results of the corresponding bone scan. In 23 patients the bone scan was positive for fracture of the scaphoid. Irrespective of training and experience, the kappa of the comparison of the scores of the radiographs between any two observers did not exceed 40 per cent. After stratification of the outcome of the bone scan, the kappa did not increase significantly. A panel of three experienced observers gave their opinion of all radiographs. The results were compared with the bone scan results. We conclude that radiographs in suspected scaphoid fracture cannot be used as a reliable diagnostic approach because of the low inter-observer agreement in the interpretation, irrespective of the experience and training of the observer.

The role of plasma D-dimer concentration in the exclusion of pulmonary embolism

Objective. To determine the role of four ELISA D‐dimer assays in the exclusion of pulmonary embolism.

The diagnostic management of suspected scaphoid fracture

The role of radiography and bone scintigraphy in the diagnostic management of patients with clinically suspected scaphoid fracture after carpal injury is reviewed. Evidence is provided that bone scintigraphy is indicated in patients with negative initial scaphoid radiographs. A normal bone scan excludes scaphoid fracture, and a positive bone scan sufficiently confirms the presence of clinically relevant scaphoid fracture. Furthermore, this review assesses the possibility on non-invasive additional radiographs, for the diagnosis or exclusion on scaphoid fracture as a means of avoiding bone scintigraphy in patients with negative first-day X-series.

Pulmonary embolism in deep venous thrombosis of the upper extremity: more often in catheter-related thrombosis

BACKGROUND Pulmonary embolism (PE) is a major complication of deep venous thrombosis (DVT) of the lower extremities. The incidence is approximately 50%. The incidence of DVT of the upper extremity (DVTUE) is increasing mainly due to the increasing use of central venous catheters. The percentage of PE secondary to DVTUE is still being investigated. METHODS The occurrence of PE in DVTUE was retrospectively analyzed in 78 patients with proven DVTUE. Furthermore, the literature was reviewed. RESULTS Of the identified patients with DVTUE 16 showed a primary DVTUE and 62 a secondary DVTUE. Secondary DVTUE was catheter-related in 41 (60%), which is 53% of all DVTUE. In this study the percentage of PE as a complication of DVTUE was 6 (95% CI: 0.2-30) in primary DVTUE, 13 (95% CI: 6-24) in secondary DVTUE and 17 (95% CI: 7-32) in catheter-related DVTUE. The relative risk for PE of catheter-related DVTUE versus other causes was 3.4 (95% CI: 0.4-53.5). The overall percentage was 12 (95% CI: 5-21). The literature review showed a percentage of 7 (95% CI: 4-9) in the retrospective studies and 17 (95% CI: 12-23) in the prospective studies. CONCLUSIONS Indwelling catheters are the most common cause of DVTUE. PE is not an uncommon complication of DVTUE, and is more common in catheter-related DVTUE. The difference between the incidence of PE in DVTUE and DVT of the lower extremity may be explained by a number of factors, such as differences in fibrinolytic activity, mechanical forces and venous flow patterns.

Radiography and scintigraphy of suspected scaphoid fracture. A long-term study in 160 patients

Radiographs of the scaphoid after injury are difficult to interpret, and bone scintigraphy is widely used to increase the accuracy of diagnosis, though many fractures suspected on scintigraphy cannot be confirmed radiologically. We have reviewed the clinical consequences, after one year, of managing suspected scaphoid fractures according to the bone-scan results. We studied 160 patients, 35 of whom had initially positive radiographs and were treated in a cast for 12 weeks. The other 125 had bone scintigraphy and were managed according to the result. After a minimum of one year 119 patients were reviewed. Scintigraphically suspected scaphoid fracture could not be confirmed radiologically in 25%. There were no cases of nonunion. The long period of immobilisation in patients with positive radiographs or positive bone scans did not influence the frequency or severity of late symptoms compared with those with a normal bone scan.

Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre-eclampsia at term? An exploratory analysis of the HYPITAT trial

Please cite this paper as: Tajik P, van der Tuuk K, Koopmans C, Groen H, van Pampus M, van der Berg P, van der Post J, van Loon A, de Groot C, Kwee A, Huisjes A, van Beek E, Papatsonis D, Bloemenkamp K, van Unnik G, Porath M, Rijnders R, Stigter R, de Boer K, Scheepers H, Zwinderman A, Bossuyt P, Mol B. Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre‐eclampsia at term? An exploratory analysis of the HYPITAT trial. BJOG 2012;119:1123–1130.

Diagnosis of deep vein thrombosis

In this chapter, various tests have been discussed in the diagnosis of DVT and have been classified according to various patient categories. To summarize, the following guidelines may be of clinical use in the management of patients with suspected DVT. Acute, First Event of Suspected DVT These patients often suffer from occluding, proximal thrombi. Therefore, noninvasive tests such as CUS or IPG are most suitable for these patients. If an abnormal CUS or IPG result is found, the diagnosis is virtually proven, and this may serve as a basis to treat the patient with anticoagulants. If a normal CUS or IPG result is obtained, serial testing is indicated to detect extending calf vein thrombi or nonoccluding DVT, which becomes occlusive at follow up. Anticoagulants may be withheld safely if the test remains normal within 1 week. Acute, Recurrent Suspected DVT These patients may have residual thrombi present, which makes the noninvasive tests (CUS/IPG) less useful. However, if a normal noninvasive test was documented previous to the acute recurrent event, this test may be used. If an abnormal test result is found in the presence of a documented, normal previous-test outcome, this may serve as a basis for anticoagulant therapy. Although no formal studies have been performed to evaluate the safety of withholding anticoagulants if a normal CUS or IPG result is obtained, serial testing is likely to be adequate in these circumstances. Phlebography is the only truly evaluated approach, and this could be considered in all suspected recurrent DVT. Furthermore, contrast venography is the test of choice to discern acute from old thrombi. Asymptomatic DVT in High-Risk Patients The majority of these thrombi are mostly localized in the calf veins only and are often nonocclusive. This makes noninvasive tests unreliable for their detection. Therefore, only contrast venography should be used in this patient category.

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.