Limitations of Impedance Plethysmography in the Diagnosis of Clinically Suspected Deep-Vein Thrombosis

Abbreviations DVTdeep-vein thrombosis IPGimpedance plethysmography Objective tests are used to diagnose deep-vein thrombosis (DVT) because its signs and symptoms are nonspecific and may be mimicked by various nonthrombotic disorders [1, 2]. Although venography is the reference standard for the diagnosis of DVT, its use has been limited because of its invasive nature and associated side effects [3-5]. For this reason there has been considerable interest in developing noninvasive diagnostic tests for DVT to replace venography [6]. Of these, occlusive cuff impedance plethysmography (IPG) was the first to be evaluated thoroughly and became one of the most widely adopted methods. Studies in the mid 1970s and early 1980s compared IPG with venography in patients with suspected DVT and reported that the sensitivity and specificity of IPG for proximal-vein thrombosis was approximately 95% [7-11]. Although IPG was found to be insensitive to DVT isolated to the calf veins, this was not considered to be an important shortcoming for three reasons: First, calf-vein thrombi do not appear to be dangerous provided that they remain confined to the calf [8, 12]; second, isolated calf-vein thrombi are uncommon in patients with symptomatic DVT [13]; and third, it was hypothesized that any calf-vein thrombi extending into the proximal veins could be readily detected by repeating the IPG test over a 7- to 10-day period. Several studies subsequently demonstrated that 14% to 26% of symptomatic patients with proven proximal-vein thrombosis had a normal IPG result at presentation but developed an abnormal test during the serial IPG testing [14-16]. These patients were presumed to have had isolated calf-vein thrombosis at the time of their initial IPG test, which was detected after it extended to the proximal veins. These studies also showed that it was relatively safe to withhold anticoagulant treatment from patients with serial normal IPG results because only about 2% of these patients developed symptomatic venous thromboembolic complications during long-term follow-up. Consequently, serial IPG testing became the method of choice for the diagnostic management of patients with clinically suspected DVT in many centers in the world. A recent report called into question the safety of withholding anticoagulants from patients with normal IPG results [17]. Prandoni and associates performed serial IPG testing in 311 patients with clinically suspected DVT whose initial IPG result was normal. Four (1.3%) of these patients subsequently developed fatal pulmonary emboli despite having normal IPG tests. At our thrombosis center, serial IPG testing has been used for many years to manage patients with clinically suspected DVT. Recently, we became increasingly aware that IPG was failing to identify an unexpectedly high number of symptomatic patients with proximal-vein thrombosis. We therefore decided to reevaluate the accuracy of IPG for the detection of proximal-vein thrombosis in symptomatic outpatients. Methods On 1 January 1990, a comprehensive computerized data base was created that prospectively recorded pertinent information on all patients evaluated at the Thrombosis Clinic of the Henderson General Hospital in Hamilton, Ontario. This data base contained information about patients' presenting symptoms, other relevant clinical and demographic data, and results of objective tests. These data were analyzed retrospectively (prompted by our impression that IPG was failing to detect some proximal-vein thrombi) in November 1991. During this 22-month period, consecutive patients with clinically suspected DVT were evaluated using a standardized protocol. All patients were assessed by a physician and underwent IPG. (Patients with previously documented DVT or pulmonary embolism were excluded from this analysis.) If the IPG result was abnormal, patients were referred for venography to confirm the presence of DVT. Patients for whom a venogram could not be obtained or whose venogram was inadequate for interpretation had compression ultrasound. Patients with a normal IPG result were managed in one of two ways: Those in whom the clinical suspicion for DVT was low had two additional IPG tests over a 7-day period, whereas those in whom the clinical suspicion of venous thrombosis was high were referred for venography. The distinction between patients at high and low clinical suspicion for DVT was made at the discretion of the individual clinicians. In general, patients were considered at high risk if their symptoms were consistent with DVT and they had one or more recognized risk factors for venous thrombosis (such as cancer or recent immobilization) and no alternative explanation for their symptoms. Patients who were unable to return to the clinic for serial IPG testing were also evaluated with venography. Two IPG instruments were used in this study (IPG 200, Codman and Shurtleff Inc., Randolph, Massachusetts, and IPG 800, Electrodiagnostic Instruments Inc., Burbank, California). Although the IPG 200 is no longer in production, it was the model used in most of the early studies evaluating IPG. The IPG 800 is the updated version of the IPG 200. Both machines use identical means to measure impedance. Impedance plethysmography was done using the occlusive cuff technique as described previously [7]. Briefly, the patient was placed in the supine position with the examined leg flexed at the knee, externally rotated at the hip and elevated 20 to 30 degrees. A pneumatic cuff was applied around the thigh and circumferential electrodes were placed around the calf. The cuff was inflated to a pressure that produced venous occlusion (45 cm H2O for the IPG 200 and 68 cm H2O for the IPG 800) for periods of 45 seconds and 2 minutes and rapidly deflated. The test was done on a maximum of five occasions and the rise in impedance occurring during cuff inflation was plotted against the fall on a nomogram. The stop line is a line on the IPG nomogram that is above and parallel to the discriminate line. If a result fell above the stop line, IPG was discontinued. In a previous study, it was shown that the risk for proximal-vein thrombosis was very low if any point on the five-test sequence fell above this line [18]. If, after the five-test sequence was completed, none of the tests was above the stop line and the test with the largest rise did not give the largest fall, then the test was considered inadequate and further tests were done. The interpretation of the IPG result was done as described previously. The test was read as normal if: 1) the test with the highest rise and fall was above the discriminant line; or 2) a test in the sequence fell above the stop line. Contrast venography was done with the patient tilted in the semi-upright position and the examined leg was nonweight bearing. Approximately 60 to 120 mL of nonionic contrast (iodine, 300 mg/mL) was injected into a dorsal foot vein. Spot films of the calf, knee, thigh, and pelvis were obtained after maximal filling with contrast material as determined by fluoroscopy. Deep-vein thrombosis was diagnosed by the presence of a constant intraluminal filling defect present in at least two projections or by nonfilling of a vein or venous segment despite repeated injections with contrast material. A thrombus was regarded as nonocclusive if contrast material was seen between the vessel wall and the thrombus along its entire course. Deep-vein thrombosis was excluded if the peroneal, posterior tibial, popliteal, superficial femoral, common femoral, and iliac veins were adequately visualized, and no filling defects were observed. Visualization of the anterior tibial veins was not required for a venogram to be considered adequate for interpretation. Venograms were considered inadequate for interpretation if opacification of the deep veins was insufficient. Proximal-vein thrombi were defined as those involving the popliteal or more proximal leg veins. The extent of proximal-vein thrombosis was categorized according to the number of vein segments involved. On a scale from 1 to 4, 1 point was given for involvement of each of the popliteal, superficial femoral, common femoral, or iliac vein segments by thrombosis. Compression ultrasound was done with a high-resolution duplex scanner (Acuson 128, Acuson Corporation, Mountain View, California) equipped with electronically focused linear array transducers (5 to 7.5 Mhz) [19]. The deep venous system of the thigh (including the entire popliteal vein) was evaluated for compressibility. Deep-vein thrombosis was diagnosed if a vein or a venous segment was not fully compressible. In patients whose DVT was diagnosed by compression ultrasound, a thrombus was determined to be occlusive if venous flow was absent by Doppler ultrasound after augmentation. Venography (or compression ultrasonography) was done in all patients with abnormal IPG results (to assess the positive predictive value) and in the subset of patients with a normal IPG result who had either a high clinical suspicion for venous thrombosis or in whom follow-up testing was inconvenient (to assess the sensitivity). Sensitivity of IPG was calculated only for proximal-vein thrombosis. The 95% confidence interval (CI) for sensitivity was determined using the binomial distribution. The size of venous thrombi in patients with false-negative IPG findings was compared with that in patients with true-positive IPG tests. To assess whether one of the IPG machines contributed disproportionately to the observed results, we calculated the sensitivity rate for each of the IPG machines separately. The Student t-test and the chi-square test were used when appropriate. Results From January 1990 to October 1991, 413 consecutive patients were evaluated for suspected symptomatic DVT. Twenty-three patients with previously documented venous thromboembolic disease were excluded from the study. The remaining 390 eligible patients were interviewed and examined by a ph