A 39-year-old woman presents to the emergency department (ED) with a non-productive cough, non-pleuritic chest pain, and shortness of breath (dyspnea). She is a smoker currently using Estrogen for hormonal abnormalities, but has no other significant past medical history. Her physical examination is unremarkable except her pulse which is mildly elevated, including clear lung auscultation and a non-tender chest wall. Although you contemplate the diagnosis of pulmonary embolism, her well appearance and normal vital signs notwithstanding pulse including normal oxygen saturation argue for bronchitis-related symptoms. You consider and then order a D-dimer study to rule in or rule out a pulmonary embolus (clot in the pulmonary arteries).
Clinical Question
Can a subset of patients with sufficiently low risk for pulmonary embolism be identified who require no diagnostic testing or should all patients that have a clinical picture to some degree consistent with pulmonary emboli be fully evaluated?
Context
Although 600,000 individuals have a pulmonary embolism (PE) identified every year, the diagnosis remains one of the most elusive for emergency physicians.(1,2) In 2003, American College of Emergency Physicians guidelines indicated that a negative D-dimer could be used to exclude PE in low-risk patient subsets. In randomized controlled trials, D-dimer testing has demonstrated favorable diagnostic test characteristics. However, D-dimer studies have high false positive rates and these false-positive rate increase with increasing age.(3,4) This is particularly important given recent concerns of radiation exposure and the subsequent need to limit computed tomography (CT) scanning.(5) Despite systematic incorporation of D-dimer testing into PE algorithms, ED diagnostic and therapeutic management often might be inappropriate, resulting in suboptimal care.(5,6) One key differentiation emergency physicians must make is low-risk from no-risk PE to avoid the potential of false-positive D-dimer results with resultant unnecessary pulmonary vascular imaging and systemic anticoagulation.
Evidence
Numerous studies have been done, the references of which are included below that demonstrate that there are exclusion criteria that identify specific populations who don't need to undergo exhaustive testing.
Conclusions
The PERC score (pulmonary embolism rule-out criteria) provides clinicians with an easily remembered, validated clinical decision rule that allows physicians to forgo diagnostic testing for pulmonary embolus in a very low-risk population. By appropriately using this tool, emergency physicians can diminish the cost, time, and ancillary test risk related to a false-positive D-dimer result with a miss rate under 1%. However, the PERC score should be applied only to low-risk PE patients, which requires application of another PE clinical decision rule, such as Well's criteria, to the general ED population with suspected PE. Using the PERC score on the general ED population will not reduce the post-test probability below 1%.
Discussion:
The detection of occult PE is a challenge. Diagnosing PE in patients with clear signs of PE (e.g., unilateral leg swelling, tachycardia, hypoxia, sudden chest pain) is usually not a mystery. Occult PE is different. It represents the diagnostic 'perfect storm:' 1) it can present atypically, 2) it may be lethal if missed, and 3) the diagnostic pathway involves a highly sensitive but poorly specific test (D-dimer) where more than half with positive D-dimers will be false positives and be subjected to the radiation of a negative chest CT scan. The recently validated PERC criteria shed new light on the challenge of occult PE by providing an intuitive rule that guides us to forgo testing in some low-risk patients. For those who intend to integrate the PERC into practice the rule is as follows:
PERC Rule for Pulmonary Embolism
|
Age < 50? |
Yes/No |
|
HR < 100? |
Yes/No |
|
O2 Sat on Room Air >94%? |
Yes/No |
|
No Prior History of DVT/PE? |
Yes/No |
|
No Recent Trauma or Surgery? |
Yes/No |
|
No Hemoptysis? |
Yes/No |
|
No Exogenous Estrogen? |
Yes/No |
|
No Clinical Signs Suggesting DVT? |
Yes/No |
|
Score |
points |
|
|
|
The PERC rule only applies if all 8 criteria are met. However there are some problems with the PERC rule as researchers have pointed out.
The first issue is the miss rate. Kline and colleagues calculated that a 1.8% (a little less than 1 in 50) miss rate was acceptable in the PERC derivation.(6) This number was based on a formula that incorporated the following risks from CT angiography: 1) cancer from radiation exposure, 2) anaphylaxis or severe pulmonary edema requiring intubation, and 3) requiring hemodialysis from the dye. It also considered the risk of death from missing a PE (defined as a 20% risk reduction for detected vs. missed). In the validation, the false-negative rate of the PERC was 1%. In English, this means that if you think a patient is low risk for PE and the patient is PERC negative, there is still a 1% chance that the patient actually has one. The question you have to ask yourself (and your patient) is: Is it really acceptable to send 1 in 100 patients home with a PE? Or, for that matter, 1.8 in 100? There is really no right answer. However, this perspective provides a more practical explanation of the risk behind the rule: PERC negative is not 100% perfect; there is still a small chance of PE.
An additional point that should be highlighted is that the PERC needs to be applied to the correct population. That is, it should be used only for 'low-risk' patients (< 15% pre-test probability). But differentiating who is truly 'low-risk' vs. 'low-risk but high-risk enough not to apply the PERC' is a difficult and subjective decision. Recent literature has demonstrated that inter-rater reliability for pre-test probability in PE is poor.(14) In addition, there may be patients who are at higher risk for PE due to other factors that were not common enough in the derivation set to be included in the PERC. For example, consider a 42-year-old woman with sudden-onset chest pain on standing after a transatlantic flight whose brother and sister both had a PE in their 40s. This patient meets the PERC criteria. Would you still order a test? What this illustrates is that applying the PERC to higher prevalence (pre-test probability) populations is associated with unacceptably high miss rates. When applying the PERC, consider the clinical scenario and ask yourself, is this patient really 'low risk?'
With these caveats in mind, we need to be practical and not throw out the baby with the bath water with important clinical decision rules like the PERC. The PERC is an important addition to the emergency medicine literature and, if used properly, may safely identify low-risk patients and prevent many from undergoing the all-too-common positive D-dimer, negative CT, 8-h-later pathway. In summary, although the PERC does not eliminate the challenge of diagnosing the occult PE, it does provide us with a compass to help navigate the waters for this complex and challenging diagnosis.
With regard to medical-legal issues, attorneys are often faced with accepting or rejecting missed pulmonary emboli cases. Each case is unique, but as you can see from the foregoing, the only sure way to be absolutely certain no patient, even low risk ones, do not have the condition is to undertake a full court press evaluation, and of course, in this day and age of cost containment and utilization management, this is not practical nor condoned by peers and hospital administrators.References
1. Chunilal SD, Eikelboom JW, Attia J, et al. Does this patient have pulmonary embolism?. JAMA. 2003;290:2849-2858.
2. Fesmire F, Kline J, Wolf S. Critical issues in the evaluation and management of adult patients presenting with suspected pulmonary embolism. Ann Emerg Med. 2003;41:257-270.
3. Kearon C, Ginsberg JS, Douketis J, et al. An evaluation of D-dimer in the diagnosis of pulmonary embolism: a randomized trial. Ann Intern Med. 2006;144:812-821.
4. Righini M, Goehring C, Bounameaux H, Perrier A. Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med. 2000;109:357-361.
5. Brenner DJ, Hall EJ. Computed tomography—an increasing source of radiation exposure. N Engl J Med. 2007;357:2277-2284.
6. Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2:1247-1255.
7. Wolf SJ, McCubbin TR, Nordenholz KE, Naviaux NW, Haukoos JS. Assessment of the pulmonary embolism rule-out criteria rule for evaluation of suspected pulmonary embolism in the emergency department. Am J Emerg Med. 2008;26:181-185.
8. Kline JA, Courtney DM, Kabrhel C, et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008;6:772-780.
9. McGinn TG, Guyatt GH, Wyer PC, Naylor CD, Stiell IG, Richardson WS. Users' guides to the medical literature: XXII: how to use articles about clinical decision rules (Evidence-Based Medicine Working Group). JAMA. 2000;284:79-84.
10. Pauker SG, Kassirer JP. The threshold approach to clinical decision making. N Engl J Med. 1980;302:1109-1117.
11. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83:416-420.
12. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED) (The PIOPED Investigators). JAMA. 1990;263:2753-2759.
13. Centre for Evidence-Based Medicine (CEBM). EBM tools. interactive nomogram. Oxford, UK: CEBM. http://www.cebm.net/index.aspx?o=1161 Accessed April 24, 2008.
14. Rodger MA, Maser E, Stiell I, et al. The interobserver reliability of pretest probability assessment in patients with suspected pulmonary embolism. Thromb Res. 2005;116:101-107.
Note: This article was excerpted and edited for brevity and additional clarity from the J Emerg Med. 2009;36(3):317-322. For a full discussion of this topic refer to this article.
