Use of a Clinical Model for Safe Management of Patients with Suspected Pulmonary Embolism

Because the signs and symptoms of pulmonary embolism are nonspecific, objective diagnostic tests are warranted when this event is suspected [1, 2]. Many algorithms have been suggested for the diagnosis of pulmonary embolism, but there is no standardized approach. Pulmonary angiography is the gold standard diagnostic test, but this technique is invasive, expensive, not readily available, and labor intensive. Moreover, its results can be difficult to interpret. In addition, 1.6% of patients with a normal pulmonary angiogram develop pulmonary embolism during 1-year follow-up, usually in the first month [3, 4]. Consequently, noninvasive ventilation-perfusion lung scanning is usually performed first in patients with suspected pulmonary embolism. A normal scan essentially rules out the diagnosis of pulmonary embolism [5], and a high-probability scan has a high positive predictive value (except in patients with a low pretest probability) [6, 7]. However, more than 50% of patients with suspected pulmonary embolism have so-called non-high-probability ventilation-perfusion scans; angiography would demonstrate pulmonary embolism in less than 25% of these patients. Given the limitations of angiography and the fact that most pulmonary emboli originate from thrombi in the deep veins of the leg [7], investigation for deep venous thrombosis by using ultrasonography is an alternative. It is relatively safe to withhold anticoagulation in patients with suspected pulmonary embolism who have no evidence of deep venous thrombosis on serial impedance plethysmography [8]; however, impedance plethysmography is not widely used, and we recently demonstrated that it is significantly less sensitive than ultrasonography [9, 10]. Two studies [6, 11] have demonstrated that clinical assessment of the pretest probability of pulmonary embolism may be a useful adjunct to lung scanning, but neither study used explicit criteria. The optimal strategy for investigating patients with suspected pulmonary embolism should combine clinical assessment, ventilation-perfusion scanning, and venous ultrasonography of the lower extremities. We reasoned that patients with non-high-probability ventilation-perfusion scans and a low or moderate pretest clinical probability of pulmonary embolism (as determined by a clinical prediction rule) could be safely managed with serial ultrasonography. Further testing would be required in patients with a high clinical probability and a non-high-probability scan and in patients with a low clinical probability and a high-probability scan. Methods Development of the Clinical Model Our group (consisting of physicians trained in respiratory medicine, hematology, thrombotic diseases, epidemiology, and radiology) previously developed a useful clinical model for patients with suspected deep venous thrombosis by reviewing the literature and coming to a consensus on a scoring system. The system combined well-established risk factors for venous thrombosis, clinical signs and symptoms, and determination of whether an alternative diagnosis was likely [12]. We applied the same strategy in patients with suspected pulmonary embolism. We used criteria from the published literature [13, 14] to establish a pilot model by consensus. This preliminary model was tested in a pilot study of 91 patients with suspected pulmonary embolism and was subsequently refined. The final clinical model is shown in Figure 1. Figure 1. Algorithm for the clinical model to determine the pretest probability of pulmonary embolism (PE). First, a history was taken and a physical examination was performed; the latter included chest radiography, oxygen saturation tests, and electrocardiography (if indicated). A checklist of signs and symptoms was completed to determine whether the patient met our definition of a severe, typical, or atypical clinical presentation. The presence of an alternative diagnosis that was as likely as or more likely than pulmonary embolism to account for the patient's signs and symptoms was determined. This determination was based on signs and symptoms and results of routine tests (blood gas, chest X radiography, or electrocardiography). We defined an alternative diagnosis as any other illness that could fit the patient's symptom complex if it was supported by the history or by physical, laboratory, and radiologic findings. The alternative diagnosis did not have to be related to previous disorders: For example, it was possible to enroll a patient with an alternative diagnosis of pneumonia if the physician still thought that pulmonary embolism could not be ruled out. Finally, established risk factors for venous thromboembolism were totalled. Patients could then be classified as having a low, moderate, or high probability of pulmonary embolism. Management Study Patient Sample Five Canadian centers [McMaster University Medical Centre and the Hamilton Civics Hospitals, Hamilton; Ottawa Civic Hospital, Ottawa; and Queen Elizabeth II Health Sciences Centre, Halifax] participated in the study from September 1993 to May 1996. Consecutive inpatients and outpatients with suspected pulmonary embolism whose symptoms had lasted less than 30 days were potentially eligible. Exclusion criteria were 1) suspected upper-extremity deep venous thrombosis as the source of the pulmonary embolism, 2) no symptoms of pulmonary embolism for more than 3 days before presentation, 3) use of anticoagulation for more than 72 hours, 4) expected survival of less than 3 months [a criterion introduced halfway through the study because the death rate, albeit not due to pulmonary embolism, was higher than expected], 5) contraindication to contrast media, 6) pregnancy, 7) geographic inaccessibility precluding follow-up, 8) age younger than 18 years, and 9) inability to obtain permission from the patient or the patient's attending physician. Investigations on the Day of Presentation After informed consent was obtained, all patients were evaluated by a physician to determine the pretest clinical probability of pulmonary embolism by using the clinical model. Ventilation-perfusion scanning was performed, and the results were interpreted by the hospitals' nuclear medicine physicians. These physicians had no knowledge of other results or the patients' signs, symptoms, or risk factors. Their scan interpretations were used to manage patients. Ventilation-perfusion scans were interpreted as 1) normal [no perfusion defects], 2) high probability ( 1 segmental or greater perfusion defects with normal ventilation or 2 large subsegmental perfusion defects [>75% of a segment]) with normal ventilation, or 3) non-high probability (ventilation-perfusion defects that did not qualify as high probability or normal) [7]. A lung segment reference chart was used to interpret the scans [15]. In a random sample of 570 patients, the scans were interpreted by using the revised Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria [16] and were compared with the results derived by using the criteria described above. After ventilation-perfusion scanning was completed, bilateral compression ultrasonography from the common femoral vein to the trifurcation of the calf veins (but not below) was performed. Lack of vein compressibility was considered diagnostic of deep venous thrombosis. Subsequent Management Strategy Patient management was based on the results of clinical pretest probability, ventilation-perfusion scanning, and ultrasonography (Figure 2). In our management strategy, patients underwent contrast venography and pulmonary angiography if the clinical pretest probability and ventilation-perfusion scan were discordant (high clinical probability with a non-high-probability ventilation-perfusion scan or low clinical probability with a high-probability ventilation-perfusion scan). Contrast venography was performed as described elsewhere [17]. If the venogram was normal, patients received intravenous heparin and pulmonary angiography was performed within 24 hours. Pulmonary angiography was performed by using standard techniques [11]. Pulmonary embolism was diagnosed if there was a constant intraluminal filling defect or an abrupt cut-off in vessels larger than 2.5 mm in diameter. Low- and moderate-probability patients with non-high-probability ventilation-perfusion scans are statistically the most likely group to have false-positive results on ultrasonography. Therefore, we attempted to perform confirmatory venography in these patients. If the venogram was inadequate or could not be obtained, the final diagnosis was made on the basis of the result of ultrasonography or angiography was performed. Figure 2. Diagnostic strategy used in patients with suspected pulmonary embolism. Patients were classified as positive for pulmonary embolism if one or more of the following occurred: an abnormal result on pulmonary angiography, ultrasonography, or venography; a high-probability ventilation-perfusion scan plus moderate or high pretest probability; or a venous thromboembolic event within the 3-month follow-up period. All other patients were classified as negative for pulmonary embolism. Treatment and Follow-up Anticoagulant therapy was withheld in patients who were negative for pulmonary embolism. Patients were followed for 3 months and were instructed to return at once if they developed symptoms or signs suggestive of pulmonary embolism or deep venous thrombosis. If at any time venous thromboembolism was suspected, patients were investigated by using a standardized approach (Figure 3). After 3 months, all patients returned for a followup appointment or were contacted by telephone. Figure 3. Algorithm for investigation of patients with suspected deep venous thrombosis or pulmonary embolism during 3-month follow-up. Statistical Analysis The primary analysis was a comparison of the rate of venous thromboembolism during the 3-month follow-up in patients who had a low or moderate pretest probability, non-h