Study Protocol

The attending physicians, who ordered / scintigraphy because they suspected pulmonary embolism, were asked to assess the clinical probability of  pulmonary embolism on the basis of  information from the patient’s clinical history, physical examination and, if available, chest radiography, electrocardiography, and arterial blood gas analysis. A visual analogue scale of 0 to 100% was used. Before the analysis, the clinical probability estimates were divided into three categories on the basis of previous literature: less than 20%, between 20 and 80% and greater than 80% (1e, 2e). Both the presence of COPD and the clinical probability estimate were recorded before any further objective testing for pulmonary embolism was performed. Furthermore,  a blood sample was taken from all patients prior to or within 24 h after initiation of anticoagulant therapy and before further objective diagnostic testing. All samples were centrifuged immediately. The plasma was then aliquoted, snapfrozen and stored at –80^o C. All samples were thawed only once. In this study, the Tinaquant assay (Boehringer Mannheim GmbH, Mannheim, Germany) was used for quantitative D-dimer analysis, according to the manufacturer’s instructions. The advised cutoff value of 0.5 µg/ml was applied.

 

Bilateral compression ultrasonography was performed to screen for deep venous thrombosis in all patients within 24 h after enrollment. Two distinct methods were used. First compression ultrasonography was performed at the inguinal ligament and the popliteal fossa. After that, examination of the superficial femoral vein and the distal popliteal vein up to  the trifurcation of calf veins was performed by the same assessor. Deep venous thrombosis was considered to be present if a vein could not be fully compressed (3e).

 

Perfusion scintigraphy was performed within 24 h of referral using 100 MBq of ^99mTc-labeled macroaggregates of albumin, and images were obtained in at least four directions. A normal perfusion scan, defined as the absence of perfusion defects or irregularities excluded PE, and no further examinations were performed. Ventilation scintigraphy using ^81mKr was performed when at least one segmental perfusion defect was seen. / scan results were classified either high probability (at least one segmental perfusion defect with preserved ventilation) or nondiagnostic (all other / defects that did not meet the high-probability criteria).

 

In all patients with an abnormal perfusion scan spiral CT angiography was performed during a 32-s single breath-hold. If patients were very dyspneic, scanning was performed during shallow breathing. A 5-mm collimation was used to scan a 16-cm volume in the caudocranial direction, from the upper level of the diaphragm to a level slightly above the aortic arch (pitch of 1, 120 kV,  200-250 mA). Image acquisition was started 20 s after intravenous injection of 900 mg/s of iodine for 40 s, and images were reconstructed every 2 mm. Each scan was interpreted on a viewing station using criteria as described by Remy and colleagues (4e). Pulmonary angiography was indicated in all patients with a nondiagnostic / scan result and in patients with a high-probability / scan result and a spiral CT scan result negative for PE. Pulmonary angiography was performed by using a digital subtraction technique, with the catheter selectively positioned in the left and right pulmonary arteries. Anteroposterior and 75ş right and left lateral views were obtained with the injection of 40 mL of nonionic contrast material at a flow rate of 20 mL/s. Complete runs were evaluated both subtracted and nonsubtracted and interpreted according to accepted criteria.

 

The complete study protocol was performed within 48 h after the perfusion scan, with a maximum time span of 24 hours between the examinations. All examinations were interpreted independently by a panel of experienced physicians who did not know the clinical status of the patient or the result of other examinations performed. The / scans were read by two nuclear physicians in consensus, the spiral CT scans and pulmonary angiograms were reviewed by two radiologists and in case of disagreement a third radiologist was consulted, whose judgment was decisive.

 

References

 

1e. The PIOPED investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. 1990. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990;263:2753-2759.

2e. Perrier A, Desmarais S, Miron MJ, de Moerloose P, Lepage R, Slosman D, Didier D, Unger PF, Patenaude JV, Bounameaux H. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999;353:190-195.

3e. Lensing AW, Prandoni P, Brandjes D, Huisman PM, Vigo M, Tomasella G, Krekt J, Wouter TC, Huisman MV, Buller HR. Detection of deep-vein thrombosis by real-time B-mode ultrasonography. N Engl J Med 1989;320:342-345.

4e. Remy-Jardin M, Remy J, Wattinne L, Giraud F. Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique--comparison with pulmonary angiography. Radiology 1992;185:381-387.