Appropriateness of Diagnostic Management and Outcomes of Suspected Pulmonary Embolism

Context A large body of high-quality medical literature supports guidelines for diagnosing pulmonary embolism. Content The authors studied 1529 patients with suspected pulmonary embolism who presented to 117 emergency departments. They compared each patient's data and the treating physician's final diagnosis with prespecified diagnostic criteria. When they diagnosed pulmonary embolism, physicians used appropriate diagnostic criteria in 92% of patients. When they ruled out pulmonary embolism, they used appropriate diagnostic criteria in only 43% of patients. Inappropriate management was strongly associated with thromboembolic events in a 3-month follow-up period. Interpretation Failure to adhere to diagnostic guidelines for pulmonary embolism has consequences. Inappropriate management occurs more often when ruling out the condition. The Editors Pulmonary embolism frequently presents a diagnostic challenge to emergency department physicians because the signs and symptoms are not specific and are very common (1). Both underdiagnosis and overdiagnosis are associated with substantial morbidity and mortality rates. Untreated pulmonary embolism can be fatal (2, 3), and overtreatment exposes the patient who does not have pulmonary embolism to an unjustified risk for major bleeding (4). In latter decades, several noninvasive diagnostic tests have been validated for patients with suspected pulmonary embolism (5). No single noninvasive test is suitable in all cases, but the combination of clinical probability and 1 or several diagnostic tests allows the physician to differentiate pulmonary embolism from other conditions with confidence in most patients (6). However, the use of clinical probability, the numerous possible test combinations, and the complexity of several diagnostic algorithms may be confusing for clinicians and pose risk for inappropriate diagnoses (7). Whether evidence-based diagnostic criteria are applied in routine clinical practice has not been extensively investigated (8). Therefore, we aimed to assess whether physicians in emergency departments routinely used evidence-based diagnostic criteria for managing patients with suspected pulmonary embolism. We also wanted to determine the risk factors for inappropriate diagnoses and whether the inappropriateness of the diagnostic criteria influenced the outcome of the patients. Methods Patients and Study Design We assessed consecutive patients with suspected pulmonary embolism who presented to 117 emergency departments (116 in France and 1 in Belgium) from 13 January 2003 to 16 February 2003 (Figure 1). All patients who underwent diagnostic testing for suspected pulmonary embolism were prospectively included. Patients were excluded if 1) the diagnosis of thromboembolic disease was documented before admission; 2) pulmonary embolism was suspected during a hospital stay of more than 2 days' duration; or 3) diagnostic testing was canceled for ethical reasons, because of rapid death, or because the patient decided to leave the hospital against medical advice. Figure 1. Flow chart summarizing the diagnostic process and 3-month outcomes. The physicians who examined the patients in the emergency department completed a standardized form to report each patient's characteristics, the clinical probability (if assessed), and the diagnostic tests that were ordered. Kidney failure was defined by a creatinine clearance of less than 0.50 mL/s (<30 mL/min) according to the CockcroftGault formula (9). Because the aim of the study was to record the diagnostic management of patients with suspected pulmonary embolism in routine practice, we did not attempt to implement any recommendation for clinical evaluation, diagnostic testing, or treatment. The study coordinator in each center completed the form at the end of the patient's hospital stay to record all of the diagnostic tests performed and the final diagnostic decision. The coordinator checked the data and retrospectively reviewed the emergency department chart to assess the exhaustivity of the inclusions in the study. A standardized questionnaire was used to interview patients at the end of a 3-month follow-up period. If a patient was unavailable by telephone, the local study coordinator contacted the individual by mail or interviewed a family member or the patient's general practitioner. Whenever a possible event was disclosed, the general practitioner was contacted; we reviewed the results of diagnostic tests and the charts of those patients who were hospitalized. According to French regulations, a participant's written consent is not required for observational studies. However, we requested that every patient orally consent to follow-up, and we informed all patients that they could request withdrawal of their personal data. The ethical committee of the University Hospital of Angers and the Socit Francophone de Mdecine d'Urgence research committee approved the study. Classification of Diagnostic Strategies The criteria for accurately confirming or excluding pulmonary embolism were defined prospectively on the basis of international guidelines and reviews published over the past 5 years (1, 5, 6, 10-14). Diagnostic criteria that were considered to be appropriate are shown in Figure 2; the results of other tests or combinations of tests were considered inappropriate. Two investigators independently analyzed each patient chart and classified the diagnostic criteria that were applied as appropriate or inappropriate. Discrepancies (n= 4) were resolved by consensus after asking the opinion of a third investigator. The test results were categorized as positive, negative, or inconclusive on the basis of the results mentioned in the patient charts. Figure 2. Judgment criteria used to classify each diagnostic process as appropriate or inappropriate according to international guidelines. Follow-up Evaluations Blinded to the diagnostic testing performed, we classified the nonfatal and fatal thromboembolic events that occurred during the 3-month follow-up period as definite thromboembolic events, possible thromboembolic events, or nonthromboembolic events. A thromboembolic event was considered to be definite if the diagnosis was objectively documented by high-probability ventilationperfusion lung scan or spiral computed tomography (CT), if venous compression ultrasonography showed deep venous thrombosis, if results of pulmonary angiography were positive, or if an autopsy confirmed the diagnosis. Pulmonary embolism was considered to be a possible cause of sudden deaths that could not otherwise be explained (12). Severe hemorrhage was defined as any bleeding that resulted in disability, hospitalization, blood transfusion, or death. Patients in whom pulmonary embolism was confirmed according to initial diagnostic testing and who did not receive anticoagulant treatment were excluded from follow-up. We also excluded from follow-up those patients in whom pulmonary embolism was ruled out but who had received anticoagulant therapy for more than 5 days; therapeutic doses were defined as those intended to achieve an international normalized ratio of greater than 2.0 (oral anticoagulant therapy) or an activated partial thromboplastin time of 1.5 to 2.5 times greater than the control value (heparin) or adequate patient weightrelated dose (low-molecular-weight heparin). Statistical Analysis All statistical analyses were performed by using SAS statistical software, version 8.2 (SAS Institute, Inc., Cary, North Carolina). We used a chi-square test and the Fisher exact test in cases of small samples to assess the association between the appropriateness of the diagnostic testing and categorical variables (Table 1). The adjusted odds ratios of inappropriateness were calculated according to a multivariable logistic regression model. We used SAS's GENMOD command to employ a generalized estimating equation model to adjust for the effect of clustering by hospital. Because emergency physicians did not measure serum creatinine levels in all patients, creatinine clearance determinations were missing in 17% of the patients; consequently, the variable of kidney failure was not included in the regression model. In patients in whom pulmonary embolism was ruled out, we used a similar method to investigate if inappropriate testing was an independent risk factor for a thromboembolic event during follow-up. For follow-up, we included in our model only those variables with a 2-sided significance level of less than 0.05; our goal was to have at least 10 outcomes for every variable in the model (15). Table 1. Characteristics of Participating Patients and Centers Role of the Funding Source The study was supported by a grant provided by the clinical research department of Pays de la Loire (Projet rgional Hospitalier de Recherche Clinique). The funding source provided feedback regarding study design but had no role in data collection, data analysis, data interpretation, or writing of the report. Results Centers and Patients The study was conducted in 117 emergency departments (23 university hospitals and 94 community hospitals). Of the participating centers, 39% admitted fewer than 20000 patients annually whereas 27% admitted more than 40000 patients annually. All centers were capable of performing plasma d-dimer measurements; 47% used quantitative enzyme-linked immunosorbent assays, 50% used quantitative latex assays, and 3% used semiquantitative assays. At least 5 days per week, venous compression ultrasonography of the lower limbs was available in 80% of the centers; spiral CT was also available in 80% of centers, of which 45% used a multidetector spiral CT scanner. Ventilationperfusion lung scans could be performed in 33% of participating centers, pulmonary angiography could be performed in 44%, and echocardiography could be performed in 91%. Written guidelines were available in 29% of the emergency departments: Eight percent used a diagnostic algorithm that included cli