Last week’s NEJM has an article, from Switzerland and France, on multidetector-row computed tomography in suspected pulmonary embolism.
Rationale
The authors state that first-generation, single-detector, spiral CT scanning is quite specific (90%) but not very sensitive (70%) for detecting pulmonary emboli. In two previous studies by their group, negative CT scans were contradicted by positive lower extremity venous duplex scans in about 8% of cases.
This has led to their suggestion that CT scanning should be accompanied by ultrasound of the legs to improve sensitivity. They quote two other studies they performed which found that patients with low or moderate clinical suspicion for PE who had negative CT and duplex scanning and who were not anticoagulated fared about as well as patients who were untreated after negative pulmonary angiography (1 to 2 percent thromboembolic events in 3 months).
The main question addressed by the authors here is: If newer generation, multidetector CT scanners are more sensitive in picking up smaller emboli (which they seem to be), then might these newer scanners obviate any need for duplex scanning? A second question they address is the role of negative d-dimer testing in excluding patients from the need for further tests.
Methods
The basic approach was to evaluate patients with suspected PE, and classify them as clinically high, intermediate or low probability for PE.
- Those who were low or intermediate had D-dimer levels drawn. If the D-dimer was normal (<500 mcg/l), no further investigation was performed, no anticoagulation was given and patients were followed up. If the D-dimer was high, both CT scanning and US were performed, and patients were treated accordingly and followed up.
- Patients with a high clinical index of suspicion did not have D-dimer levels drawn but were evaluated by CT and US. If both of these studies were negative, these patients underwent pulmonary angiography.
The results were then analyzed to see how many patients had negative CT scans but positive US exams, and also to see how patients who were not anticoagulated fared.
Results
756 patients were included in the study. Of these, 674 had low or intermediate clinical probability of PE, and 82 had a high probability.
- Of the 674 who had low or intermediate probability
- 232 had negative D-dimers, and were not anticoagulated. There were no subsequent venous thromboembolic events in this group.
- 442 had positive D-dimers and were evaluated with CT and US.
- In this group, there were only 2 patients with negative CT scans but positive US examinations.
- Both tests were negative in 318 patients, and they were not anticoagulated. At three month follow-up, there were 3 non-fatal thromboembolic events and 2 deaths, possibly from PE
- 109 patients had a positive CT scan (with or without positive US), and were anticoagulated
- 13 had inconclusive CT scans (most underwent VQ scanning)
- Of the 82 with high probability
- 78 had a positive CT scan
- 3 had negative CT scan and negative US; all three had negative angiograms
- 1 patient had negative CT scan but positive US
Comments
The narrower question addressed here is whether or not multidetector spiral CT is sufficiently sensitive to obviate a postulated need for duplex ultrasound scanning in the diagnosis of suspected PE. In this study, out of a total of 324 patients with negative CT scans, there were 3 positive ultrasound examinations (0.9%), which is much lower than the 6-9% which the authors report for conventional spiral CT (from previous studies by their group).
It is important to note that more sensitive diagnosis of PE does not necessarily translate into markedly better clinical outcomes, since the clinical course of untreated small, peripheral emboli will not be as poor as that of more easily detected, central emboli.
Interestingly, a meta-analysis just published (in last week’s JAMA) looking at outcome studies using CT scanning in suspected PE failed to find a benefit of multidetector vs. single detector, and also failed to find a benefit to the addition of other modalities (such as duplex scanning), in terms of clinical outcome. Both of these points are in contradiction to the main arguments of the current study, but of course all the caveats of meta-analyses apply here.
Having said this, it does seem reasonable that the addition of ultrasound to multidetector CT scanning adds little to the diagnosis and is probably overkill. Whether it is necessary to replace single detector scanning with multidetector scanning in order to safely rule out PE and eliminate a postulated need for duplex ultrasound is much less clear to me.
The broader question addressed by this study is the overall safety of using the approach outlined here, including d-dimer testing in patients who have low or intermediate clinical probability of PE and performing CT scans only in those with positive d-dimers. In this study, had the d-dimer assay and multidetector CT scanning without duplex US been performed, the overall rate of thromboemboli in patients not anticoagulated would have been 1.5%, comparable to the rate for patients with negative pulmonary angiograms. The authors suggest that this strategy should be prospectively evaluated.