PERC Rule: Application and Limitations

Intro

Kline et al1 developed a clinical decision tool based on parameters that could be obtained from a brief initial assessment to reasonably exclude the diagnosis of pulmonary embolism (PE) without the use of D-dimer in order to prevent unnecessary cost and the use of medical resources.

The PERC rule includes:

Age < 50
Heart rate < 100
Oxygen saturation on RA > 94%
No prior history of DVT or PE
No recent trauma or surgery
No hemoptysis
No exogenous estrogen
No clinical signs suggestive of DVT

If all criteria are met, then the patient can be called “PERC ruled out” or “PERC rule inclusive.”

A review and meta-analysis published in the Annals in 20122 found 12 qualifying studies evaluating the PERC rule and ultimately determined that the pooled sensitivity to rule out pulmonary embolism is 97.2%, which the authors concluded to be a low, but acceptable sensitivity to rule out PE without further testing. The pooled negative LR was 0.17. The overall proportion of missed PEs was 0.32% (44 of 13,855 total cases).

So who are the CT-PE or V/Q positive patients who could have been falsely “PERC ruled out?” In other words, when does the PERC rule fail?

Kline reworked the data from a previous paper showing the outcomes of patients who presented to the ED and were diagnosed with PE3, and used it as a dataset to determine the characteristics of patient who received an ED diagnosis of PE, but could have been included in the PERC clinical decision tool. The initial study was used to determine that the overall mortality attributed to PE was 1%, the mortality from hemorrhage was 0.2%, and the all-cause 30-day mortality was 5.4%. In the reworking of this dataset of 1,880 patients, Kline et al4 found that 114 would have been included in the PERC rule should it have been applied.

Of these patients, they found that only 3 variables that demonstrated a true difference in the proportions between those who would have been included within the PERC rule and those who would have not been able to be “PERC ruled out”: pleuritic chest pain, pregnancy, and postpartum status. Specifically, pleuritic chest pain, which is not included in any clinical decision rule to risk stratify potential PE patients, was found in 56% of the patients where the PERC rule would have failed. Although the N numbers were small for pregnancy and postpartum status, they concluded that the PERC rule should not be used in isolation to rule out PE in patients who are either pregnant or postpartum. Again, it should be noted that pleuritic chest pain is not a component of either the Wells PE or revised Geneva score for PE.

And the reason for its absence in these scores could be considered questionable. A large study including nearly 8,000 patients of whom 7.2% had PE by Courtney et al published in Annals in 20105 was designed to study the variables commonly believed to modify the pretest probability of PE and those already within the existing pretest probability scores. The odd ratio (OR) for pleuritic chest pain in patients diagnosed with PE was 1.53, which seems weak in comparison to the ORs for history of PE and unilateral leg swelling, which are 2.9 and 2.6, respectively. However, the ORs for hemoptysis and tachycardia (defined in this study as a pulse of > 94) are 0.78 and 1.52. Both of these factors are included in the Wells PE score and the revised Geneva score. Excluding hemoptysis and tachycardia, however, all variables used in the Wells PE score have higher ORs than pleuritic chest pain. The next closest OR of the variables included in the Wells PE score is immobilization with an OR of 1.72. The authors also found that the other two variables not included in clinical decision rules with useful ORs were a personal history of non-cancer related thrombophilia (OR 1.99) and a family history of PE (OR 1.51).

The original Kline manuscript1 excluded patients with beta blockers that might be masking tachycardia, yet not all of the follow-up studies included in the recent meta-analysis excluded patients on beta blockers, so the role that current treatment with beta blockers play in determining whether or not you can use the PERC rule on a beta-blocked patient is unclear.

It is important to note that the PERC rule was never intended to be applied to anything but a low-risk group of patients determined either by clinical gestalt or by the Wells PE score, and this point has been stressed in commentary.6 Only after knowing and applying the Wells PE score, an alternative method of risk stratification, or your clinical gestalt should you consider the PERC Rule in a patient you believe is at low risk for PE. As some of the leaders of our field have pointed out, if you believe that your patient population has a higher prevalence of both DVT and PE than the general population in which these rules were derived, then our use of these decision rules, however well-validated in the literature, should be employed with some hesitance.

In fact, the meta-analysis found some heterogeneity in the PERC rule sensitivity to exclude PE. Two studies from European populations with a prevalence of PE ranging from 21-30%7,8 found that a negative PERC rule combined with the low risk Revised Geneva Score only reduced the prevalence of PE in the studied patients to 6%. Only in one of these studies,7 did the PERC rule combined with clinical gestalt reduce the prevalence of PE down to nearly zero.

The prevalence of PE in your community will determine the NPV of the PERC rule where you are practicing, and it is suggested that the PERC rule only be utilized where the prevalence of PE is less than 7 percent.9 Most of the well-designed PE literature indicates that the PE prevalence in the US is around 6%.1

Teaching Points

  • The PERC rule cannot be a substitute for gestalt.
  • Gestalt or some form of risk stratification should be employed first before using the PERC rule.
  • The PERC rule should not be used in isolation to rule out PE in pregnant or postpartum patients.
  • It is unclear if patients on beta blockers can be included in the PERC rule, and this significance has yet to be borne out in the data.
  • The meta-analysis pooled negative LR is 0.17, which gives you a maximum pretest probability of about 15% to apply the PERC rule to risk stratify your patient down to the standard risk of 2%. However, your PE prevalence must be 7% or less (essentially a Wells < 2) before the PERC rule can be applied to patients presenting to ED with suspected PE in conjunction with clinical judgment to identify patients with a prevalence of PE that is below the 1.8% test threshold proposed by Kline.
  • In high PE prevalence populations (which based on the literature, seem to be in Europe) the PERC score inclusive patients will not be able to have a post-test probability at or below the accepted standard risk level.
  • The only evidence we have about PERC rule-inclusive CT-PE or V/Q positive patients suggests that 56% of those will have pleuritic chest pain, which is not in a validated clinical decision rule despite having a higher OR for PE than hemoptysis and recent immobilization, which are both included in the Wells score.

References / Further Reading

  1. Kline JA, Mitchell AM, Kabrhel C, et al. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2:1247-1255.
  2. Singh, et al. Diagnostic Accuracy of Pulmonary Embolism Rule-Out Criteria: A Systematic Review and Meta-analysis. Ann Emerg Med. 2012;59:517-520.3.
  3. Pollack CV, et al. Clinical Characteristics, Management, and Outcomes of Patients Diagnosed With Acute Pulmonary Embolism in the Emergency Department Initial Report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol. 2011 Feb 8;57(6):700-6.
  4. Kline JA, et al. Clinical Features of Patients With Pulmonary Embolism and a Negative PERC Rule Result. Ann Emerg Med. 2013 January 60(1): 122-124.
  5. Courtney DM, et al. Clinical features from the history and physical examination that predict the presence or absence of pulmonary embolism in symptomatic emergency department patients: results of a prospective, multi-center study. Ann Emerg Med. 2010 April 55(4): 307–315.
  6. Bossart PJ. Misuse of the Pulmonary Embolism Rule-Out Criteria. Ann Emerg Med. 2012 December 60(6): 820.
  7. Penazola A, et al. Performance of the Pulmonary Embolism Rule-out Criteria (the PERC rule) combined with low clinical probability in high prevalence population. Thrombosis Research. 2012: e189–e193.
  8. Hugli O, Righini M, Le Gal G, Roy P-M, Sanchez O, Verschuren F, Meyer G, Bounameaux H, Aujesky. The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude pulmonary embolism. J Thromb Haemost. 2011; 9: 300–4.
  9. Rhenberg JV, Vondy A. BET 3: Pulmonary embolism rule-out criteria (PERC) for excluding pulmonary embolism. Emerg Med J. 2014 Jan;31(1):81-2.
  10. http://www.ncbi.nlm.nih.gov/pubmed/23167851
  11. http://www.ncbi.nlm.nih.gov/pubmed/22720850
Edited by Alex Koyfman, MD

2 thoughts on “PERC Rule: Application and Limitations”

  1. Great elucidation.
    Brings things into focus.
    The “3Ps” [Pleuritic CP/Preg/Postpartum] are not mentioned enough.
    Pleuritic CP 56% failure in PERC, I did not know about.
    Pleuritic CP Red Flag, even though it is a relative common complaint in the ED.

    Thank you!

  2. Great elucidation.
    Brings things into focus.
    The “3Ps” [Pleuritic CP/Preg/Postpartum] are not mentioned enough.
    Pleuritic CP 56% failure in PERC, I did not know about.
    Pleuritic CP Red Flag, even though it is a relative common complaint in the ED.

    Thank you!

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