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Three Part Question

In [adult patients presenting to the Emergency Department (ED)] are the [PE-rule out criteria (PERC)] sufficient to [exclude the diagnosis without the need for a D-dimer]?

Clinical Scenario

A 25-year-old man presents to the ED complaining of pleuritic chest pain and shortness of breath. He is afebrile, has no other symptoms, takes no medications and has never had any surgery. You wonder whether a clinical decision rule such as the (PERC could help exclude PE without the need for D-dimer testing.

Search Strategy

The Cochrane Library issue 10 of 12 October 2013: ‘(Pulmonary Embolism’ [MeSH; explode all trees] AND ‘Diagnosis’ [MeSH term; explode all trees]) OR (‘PERC’ OR ‘PE rule out criteria’ OR ‘Pulmonary embolism rule out criteria’ OR ‘PE rule-out criteria’ OR ‘Pulmonary embolism rule-out criteria’ OR ‘PE rule out’ OR ‘Pulmonary embolism rule out’ OR ‘PE rule-out’ OR ‘Pulmonary embolism rule-out’).

Medline/EMBASE from 2004 to 29th October 2013 using NHS Evidence interface:

‘PERC’.ti,ab OR ‘PE rule out criteria’.ti,ab OR ‘Pulmonary embolism rule out criteria’.ti,ab OR ‘PE rule-out criteria’.ti,ab OR ‘Pulmonary embolism rule-out criteria’.ti,ab OR ‘PE rule out’.ti,ab OR ‘Pulmonary embolism rule out’.ti,ab OR ‘PE rule-out’.ti,ab OR ‘Pulmonary embolism rule-out’.ti,ab Limit to: English Language

Search Outcome

Altogether, 291 papers were found in Medline and 140 in Cochrane, of which 418 were irrelevant or of insufficient quality (including one non-systematic review). A further four papers were found by scanning the references of relevant papers. One recent systematic review and meta-analysis was found looking at the other 12 relevant papers identified (including the three papers assessed in the non-systematic review). No relevant papers published after the systematic review

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Singh et al, 2012, USA	14 844 Patients from 12 studies including 13 cohorts (3 retrospective, 10 prospective) in 6 countries	Systematic review and meta-analysis of clinical decision rule (Level 2a evidence)	Diagnosis of PE or VTE or death caused by VTE within 90 days of ED evaluation	Sensitivity: 0.97 (95% CI 0.96 to 0.98); specificity: 0.22 (95% CI 0.22 to 0.23); positive likelihood ratio: 1.22 (95% CI 1.16 to 1.29); negative likelihood ratio: 0.17 (95% CI 0.13 to 0.23)	No sensitivity analysis reported. Significant heterogeneity in specificity. Differences in exclusion criteria. Patient follow-up <90 days in 4 studies included. Two studies not included on methodology checklist table (Courtney, Critchlow)

Comment(s)

The PERC rule consists of eight variables applied as a block rule: age <50 years, pulse <100, SO2 ≥95%, no haemoptysis, no oestrogen use, no surgery/trauma requiring hospitalisation within 4 weeks, no previous venous thromboembolism, no unilateral leg swelling. It was developed in 2004 to identify ED patients of low enough risk to eliminate the need for D-dimer testing to exclude PE (Singh).At the same time as deriving the PERC rule, Kline et al calculated a test threshold for PE, calculated as the level at which the risks of further investigation and its implications (ie, contrast-enhanced imaging and therapeutic anticoagulation) outweigh the risks of missed PE. This test threshold was calculated as a pre-test probability of 1.8%, thus suggesting that patients with a pre-test probability below this level should not undergo further investigation (Singh)

Clinical judgement and other factors may demand further testing despite a negative PERC (eg, thrombophilia, family history of thromboembolism, use of β-blockers masking tachycardia, obesity or amputation preventing accurate assessment of unilateral leg swelling, chronic hypoxaemia with SO2 <95%, etc). There were differences in exclusion criteria and length of follow-up in the included studies, which could influence the overall results and their validity in some patients. There was no reported sensitivity analysis and the potential for publication bias was not assessed. Higher rates of missed PE in two studies were attributed to an increased prevalence of PE in their studies but the authors’ own meta-regression analysis found no significant difference in PERC performance based on PE prevalence. Overall, the paper was rigorous and explicit in its search strategy, study inclusion criteria and assessment of methodological quality. The high sensitivity and low negative likelihood ratio (NLR) seem to indicate that the PERC rule could be safely used to exclude PE. However, the upper confidence limit for the NLR (0.23) applied to the prevalence of PE in the study group (10%, odds 0.11) gives a probability of PE above the 1.8% threshold (2.5%, odds 0.0256). Using this upper limit the highest prevalence in which PERC could reliably exclude PE without further testing is approximately 7%. As the prevalence of PE in patients with a Wells score <2 is 5.7%,(Courtney) these findings suggest that the performance of PERC in patients with a Wells score <2 is likely to be satisfactory. Notably, however, the pooled specificity of PERC in the entire cohort was 22%. By applying the rule only to low-risk patients, overall specificity will be further reduced. Thus PERC will ‘rule out’ PE in a minority of patients. It is possible that, when used in practice, clinicians will apply PERC to patients who would not have otherwise had a suspected diagnosis of PE. Further evaluation of the impact of the rule in practice is therefore necessary to ensure that investigation rates are successfully reduced.

Editor Comment

ED, emergency department; PE, pulmonary embolism; VTE, venous thromboembolism.

Clinical Bottom Line

In populations with a PE prevalence of 7% or less (equivalent to Well's score of <2), the PERC rule can be applied to patients presenting to ED with suspected PE, in conjunction with clinical judgement, to identify patients with a prevalence of PE that is below the 1.8% test threshold proposed by Kline et al.

References

1. Singh B, Mommer SK, Erwin PJ, et al. Diagnostic Accuracy of Pulmonary Embolism Rule-Out Criteria: A Systematic Review and Meta-analysis. Ann Emerg Med 2012;59:517-520.
2. Courtney DM, Pribaz JR, Senh AC. Prospective evaluation of the pulmonary embolism rule-out criteria PERC) rule: an 8-variable block rule to identify subjects at very low risk of pulmonary embolism. Acad Emerg Med 2006;13:S157–8.
3. Crichlow A, Cuker A, Matsuura AC, et al. Underuse of clinical decision rules and D-dimer testing in the evaluation of patients presenting to the emergency department with suspected venous thromboembolism. Acad Emerg Med , Annual Meeting of the Society for Academic Emergency Medicine; Boston, MA, 1–5 June 2011.
4. Ceriani E, Combescure C, Le Gal G, et al. Clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis. J Thromb Haemost 2010;8:957–70.