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If you missed Sohan’s last lecture as a resident, the June 4th  Journal Club, well, here’s a brief recap. For those of you who were there for his tour-de-force, you’ll no doubt want to refer to these notes from his talk in your future practice.

Sohan discussed the original PERC rule derivation paper and its recent validation — the papers below are accessible using our password system:

Kline JA, et al. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost 2004; 2: 1247–55. (PMID: 15304025)

Kline JA, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost 2008; 6: 772–80. (PMID: 18318689).

Sohan started with a lit review, going back to DeBakey’s 1954 discussion of 3 million PE’s, where it was first noted that PE is tough to diagnose and its prevalence is unclear. Even now, very little has changed. We don’t know the true incidence, we don’t know how many we miss, we don’t know which PE’s are clinically relevant, and we don’t know when to pursue this diagnosis. Even the Well’s criteria, which I mentioned here a couple of years ago, are not too clean — because they give more points to the physician’s judgment than to any other sign or lab result.

So we’ve been left with the unfortunate, all-to-common situation of considering D-dimers for every poor patient who presents with vague chest discomfort or dyspnea. If that dimer is positive, and it often is falsely so, we’re forced down a road of angiography , contrast, radiation, and other potential sources of morbidity.

Is there a way out of this? Is there a simple decision rule we can apply, at the bedside, using nothing but history and physical, to prevent this unnecessary testing?

Kline et al thought so — and the rule they proposed is discussed below.

The PERC Rule of eight variables was designed to offer pre-test probability of < 1.8% of PE, which has been previously determined to be the point of equipoise (in other words, if the probability of PE is less than 1.8%, it’s not worth it to the patient or society to press forward with testing). How do we get to 1.8%? If you can say “yes” to ALL EIGHT of these variables, and your clinical gestalt says PE is unlikely, well, you can safely discontinue future testing:

Age < 50
Pulse < 100
SaO2 > 94%
No unilateral leg swelling
No hemoptysis
No recent surgery
No prior PE or DVT
No oral hormone use

The 2004 ‘derivation’ study took 21 variables and whittled it down to the eight above using complex math (interestingly, classical risk factors for PE like smoking, malignancy, and rapid onset didn’t make the cut).

They validated this rule in 2004 with a low-risk group (made up of patients who needed a d-dimer) and a very low-risk group (patients who had dyspnea but PE was not a top consideration). Kline and company found the PERC rule was positive in 109 of 114 PE cases, giving it a sensitivity of 96% and specificity of 27%. The very low-risk group was even better, because PERC was positive in each of 9 PE cases (no false negatives).

Then, the authors go on to say a couple of contradictory things:

“We offer the PERC rule to compliment [sic] clinical judgement rather than replace it…. The [PERC] rule may be negative when a host of other factors not included in the rule may demand that the patient be tested further.”

“When all 8 factors are negative, the pretest probability of PE is likely to be so low that D-dimer testing will not yield a favorable risk-benefit ratio.”

But this is where we stood, for four long years.

Then, this spring, Kline et al released a new validation of PERC. This was a prospective, multicenter trial (12 US ED’s and one in New Zealand). Enrollment was triggered by d-dimer testing or imaging in a more-or-less consecutive sampling of adults, except in those who had a recent positive PE study, or would be difficult to follow up (which might be convenient for the authors but excludes international travelers and the homeless, two populations we see often).

They looked at how patients defined as “very low risk for PE” fared within 45 days of testing – with very low-risk defined as passing the PERC, plus physicians having a low clinical gestalt (<15% likely) for PE (so much for a “cleaner” test than Well’s criteria – but more on this later).

They made ED physicians fill out a long, long web form that had way more questions on it than just the PERC data fields, and dubbed patients as having venous thromboembolus if they tested positive PE by VQ, CTA or angio, or if they had a DVT on duplex or CTV. Followup was done at 45 days, in person, phone or mail, or by talking to a PMD, or by reviewing death indices and autopsy results.

8138 patients were enrolled – 2/3 of which were classified as “low probability” by physician assessment. 561 of these patients ended up with VTE, for a prevalence of 6.9% (lower than the 11% from the 2004 derivation study).

When the PERC rule was applied to low-risk patients, it was found to be 97.4% sensitive, 21.9% specific, and passing the PERC rule meant gave a likelihood ratio of 0.12 for PE – a pretty good. Heck, even just applying the PERC rule to patients NOT deemed to be low-risk by ED docs led to a LR of 0.17.

In our discussion, the big problems we had with the paper centered on the 304 patients lost to followup, which came after the decision to exclude patients that seemed hard to reach in the future. When you consider that, coupled with some PMD’s lack of aggression in working up dyspnea, we’re still not sure we can comfortably estimate the prevalence of PE, in general or in the population that passed the PERC rule. But, as many discussants noted, this is a very satisfying rule to use clinically, as it gives weights to the factors that make up ‘clinical gestalt’ and, in time, might redefine our collective judgment of the likelihood of PE.

There’s more discussion of the PERC rule and PE testing in general at EMcrit.org , and ACEP has a clinical policy on this matter as well.

Posted on Friday, June 6th, 2008 at 8:05 pm by Nick. Filed under Pulmonary Embolism, Risk Stratification, Journal Club, Blog.
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