Journal club this month at my institution involved the literature behind the derivation and validation of the PERC (Pulmonary Embolism Rule-Out Criteria) Rule. So, as faculty, to be dutifully prepared, I read the articles and a smorgasbord of supporting literature – only to realize I’m working the conference coverage shift. Rather than waste my notes, I’ve turned them into an EMLit mega-post.
Derivation
The derivation of the PERC rule in 2004 comes from 3,148 patients for whom “an ER physician thought they might have Pulmonary Embolism”. Diagnosis was confirmed by CTA (196 patients), CTA + CTV (1116), V/Q (1055) + duplex U/S (372), angiography (11), autopsy (21), and 90-day follow-up (650). 348 (11% prevalence) were positive for PE. They then did a regression analysis on those patients and came up with the PERC rule, the eight-item dichotomous test for which you need to answer yes to every single question to pass.
The test case for the derivation came from 1,427 “low-risk” patients that were PE suspects, and as such, had only a d-Dimer ordered to rule-out PE – and in whom a CTA was performed when positive. 114 (8% prevalence) had PE. There was also an additional test case of “very low-risk”, 382 patients from another dyspnea study who were enrolled when “an ED physician thought PE was not the most likely diagnosis.” 9 (2.3%) of the very low-risk cohort had PE.
Performance on their low-risk test set was a sensitivity of 96% (CI 90-99%) with a specificity of 27%. On their very low-risk test set, sensitivity was 100% (59-100%) with a specificity of 15%.
Validation
Multicenter enrollment of 12,213 with “possible PE”. 8,183 were fully enrolled. 51% underwent CTA, 6% underwent V/Q, and everyone received 45-day follow up for a diagnosis of venous thromboembolism. Overall, 6.9% of their population was diagnosed with pulmonary embolism.
Of these, 1,952 were PERC negative – giving rise to a 95.7% sensitivity (93.6-97.2%). However, the authors additionally identify a “gestalt low-risk” group of 1,666 that had only 3.0% prevalence of PE, apply the PERC rule to that, and come up with sensitivity of 97.4% (95.8 – 98.5%).
The authors then conclude the PERC rule is valid and obviates further testing when applied to a gestalt low-risk cohort in which the prevalence is less than 6%.
Other PERC Studies
Retrospective application of PERC to another prospective PE database in Denver. Prevalence of PE is 12% of 134 patients. Only 19 patients were PERC negative, none of whom had PE. Sensitivity is 100% (79-100%).
Retrospective application of PERC to patients receiving CT scans in Schenectady. Prevalence of PE was 8.45% of 213. 48 were PERC negative, none of whom had PE. Sensitivity is 100% (79-100%).
Effectiveness study of PERC in an academic ED (Carolinas). 183 suspected PE patients, PERC was applied to 114, 65 of whom were PERC negative. 16 of the PERC negative underwent CTA, all negative. 14 day follow-up of the remaining 49 also indicated no further PE diagnosis. No sensitivity calculation.
Retrospective application of PERC to prospective PE cohort in Switzerland. Prevalence of PE was 21.3% in 1,675 patients. In the 221 patients who were PERC negative, 5.4% had PE (3.1 – 9.3%) for a sensitivity of 96.6 (94.2 – 98.1%). The subset of PERC negative who were also low-risk by Geneva Score actually had a higher incidence of PE at 6.4%.
Summary
So, PERC can only be applied to a population you think is low-risk for PE – for which you can use clinical gestalt or Wells’ – because it looks like Wells low-risk is 1.3% (0.5-2.7%) to 2% (0-9%). But, you can’t use Geneva because that prevalence is closer to 8% for low-risk – and that’s essentially what the Swiss study shows.
But in this already very low-risk population, the question is, what is the role of PERC? Clinical gestalt in their original study actually worked great. Even though clinicians were only asked to risk stratify to <15%, they risk stratified to 3.0% prevalence of PE. Which, of course, means our estimation of the true risk of pulmonary embolism is absolutely bonkers. If you take a gestalt or Wells’ low-risk population, apply PERC, and it’s negative – your population that nearly universally didn’t have a PE still doesn’t have a PE, and it doesn’t get you much in absolute risk reduction. You probably shouldn’t have even considered PE as a diagnosis other than for academic and teaching reasons if they’re Wells’ low-risk and PERC negative.
Then, if you take the flip side – what happens if your patient is PERC positive? You have a low-risk patient whose prevalence for PE is probably somewhere between 1 and 5%, and now you’ve got a test with a positive LR of 1.24 – it barely changes anything from a statistical standpoint. Then, do you do a d-Dimer, which has a positive LR between 1.6 and 2.77? Now you’ve done a ton of work and painted yourself into a corner and you have to get a CTA on a patient whose chance of having a PE is still probably less than 10%.
That’s where your final problem shows up. CTA is overrated as a diagnostic test for pulmonary embolism. In PIOPED II, published 2006 in NEJM, CTA had 16 false positives and 22 true positives in their low risk cohort – 42% false positive rate – and this is against a reference standard for which they estimated already had a 9% false positive and 2% false negative rate. CTA is probably better now than it once was, but it still has significant limitations in a low-risk population – and I would argue the false positive rate is even higher, given the increased resolution and ability to discern more subtle contrast filling defects.
So, this is what I get out of PERC. Either you apply it to someone you didn’t think had PE and it’s negative and you wonder why you bothered to apply it in the first place – or you follow it down the decision tree and you end up at a CTA for whom you can flip a coin to believe whether the positive result is real or not.
And, I don’t even want to get into the clinical relevance of diagnosis and treatment of those tiny subsegmental PEs we’re “catching” on CTA these days.
“Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism”
www.ncbi.nlm.nih.gov/pubmed/15304025
“Prospective multicenter evaluation of the pulmonary embolism rule-out criteria”
www.ncbi.nlm.nih.gov/pubmed/18318689
“Assessment of the pulmonary embolism rule-out criteria rule for evaluation of suspected pulmonary embolism in the emergency department”
www.ncbi.nlm.nih.gov/pubmed/18272098
“The Pulmonary Embolism Rule-Out Criteria rule in a community hospital ED: a retrospective study of its potential utility”
www.ncbi.nlm.nih.gov/pubmed/20708891
“Prospective Evaluation of Real-time Use of the Pulmonary Embolism Rule-out Criteria in an Academic Emergency Department”
www.ncbi.nlm.nih.gov/pubmed/20836787
“The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude pulmonary embolism”
www.ncbi.nlm.nih.gov/pubmed/21091866
“Multidetector Computed Tomography for Acute Pulmonary Embolism”
www.ncbi.nlm.nih.gov/pubmed/16738268
“D-Dimer for the Exclusion of Acute Venous Thrombosis and Pulmonary Embolism”
www.ncbi.nlm.nih.gov/pubmed/15096330