A 15-year-old female presents to the paediatric emergency department complaining of pleuritic right-sided chest pain and mild shortness of breath since this morning.
She has no chronic medical conditions, no recent surgeries, and no leg swelling. She recently had an 8-hour flight.
Her heart rate is 98bpm, saturating 98% on room air with RR 16 and has a CXR with normal findings.
The voice in the back of your head whispers pulmonary embolism, but you want to safely rule it out at the bedside without pulling the trigger on an imaging cascade.
Until recently, we have been forced to extrapolate adult guidelines to kids. Recently, a PECARN study, the Bedside Exclusion of Pulmonary Embolism Without the Need for Radiation in Children (BEEPER) study, may give us the validation we’ve been waiting for to use the PERC-Peds rule.
Background
Pulmonary embolism (PE) in children is rare, but delayed or missed diagnosis can lead to morbidity and mortality. Currently, there is no prospective study to guide clinician evaluation of suspected pediatric PE. Also, there are no validated pediatric PE rule-out strategies, and adult diagnostic pathways have not been prospectively tested in children.
The estimated annual incidence of pulmonary embolism in the United Kingdom in the general population of non-hospitalised children ranges from 0.14 to 0.21 per 10,000 children.
There are two peaks in the overall incidence of pulmonary embolism in children: one in infants less than one year and the other in adolescence.
There have been no prior prospective data published to guide clinicians in the diagnosis of pulmonary embolism in children.
The Research question:
Can the PERC-Peds rule safely exclude pulmonary embolism or proximal DVT in children 4 to 17 years old considered to be at risk for pulmonary embolism by emergency department physicians?
What is the PERC-Peds rule?
The rule was based on the adult Pulmonary Embolism Rule-out Criteria (PERC), used to exclude PE in low-risk patients without additional blood testing or imaging studies. Using paediatric data (based on retrospective cohort studies), researchers created the PERC-Peds rule.
In order to be considered PERC-Peds negative, a child should fulfil all the following criteria:
Clinician gestalt: Estimated pretest probability of PE is less than 15%.
Medical history: No prior history of pulmonary embolism or deep vein thrombosis (DVT).
Surgery/Trauma: No surgery requiring endotracheal intubation within the past 30 days.
Medication: No current estrogen use.
Symptoms: No coughing up blood (hemoptysis).
Heart rate: Maximum heart rate is < 100 beats per minute for patients older than 12 years, or < 120 beats per minute for patients ≤12-years-old.
Oxygen saturation: > 94% on room air.
Physical signs: No clinical signs or suspicion of deep vein thrombosis (DVT).
Population
Paediatric patients aged 4-17 presenting to the emergency department with a clinical suspicion of a pulmonary embolism or proximal DVT prompting clinicians to order diagnostic testing (D-dimer, CT pulmonary angiography (CTPA), V/Q scan, MR angiography or other pulmonary vascular imaging) or strongly consider PE in the differential diagnosis.
Intervention
The newly proposed PERC-Peds decision rule with eight specific clinical risk features.
Comparison
None
Outcome
Safe exclusion of a life-threatening pulmonary embolism or proximal DVT, with a false-negative rate below the threshold of 1.5%.
Trial design
A multi-centre, prospective, observational, diagnostic-accuracy study was conducted in 21 paediatric emergency departments across the USA.
What did they find out?
BEEPER looked at what happens when a clinician suspects a clot and initiates an evaluation through medical decision-making, D-Dimer testing or imaging.
- 4,039 children enrolled, while 3,988 had complete data
- 2567 (64%) were female
- Median age 15 years (IQR 13-16)
- 678 (16.9%) were <12 years-old
So, here are the precise adjudicated results of the children who completed the 45-day follow-up:
Paediatric venous thromboembolic event (VTE) prevalence
- 254 children (6.3%) had PE and/or proximal DVT.
- Out of all the symptomatic children where a clinician actively considered a PE, 4.2% were objectively diagnosed with a VTE.
- 2.1% presented with isolated pulmonary embolism, 1.1% with isolated DVT and 1.0% with simultaneous PE and DVT.
- The median age of the affected population was 15 years; the majority were females
Diagnostic performance of PERC-Peds without D-dimer
- Sensitivity of 99.6% (95% CI 97.8–100.0%)
- Specificity of 19·6% (95% CI 18.4–20.9%)
- False negative rate of 0.1% (95% CI 0–0.8%) – below the pre-specified clinical safety threshold of 1.5%
- Negative predictive value of 99.9% (99.2–100.0)
Out of all the children categorised as ‘low-risk’ by the PERC-peds rule, only one patient was subsequently diagnosed with a missed PE.
D-dimer diagnostic accuracy
The threshold was 500 ng/mL, and D-dimer was ordered in 75–79% of enrolled children.
- Sensitivity of 89.8% (95% CI 84.8–93.7)
- Specificity of 61.9% (95% CI 59.5–63.1)
- False negative rate of 1.2-1.4%
- Negative predictive value of 98.9% (95% CI 98.3–99.3)
D-dimer was valuable as part of a sequential diagnostic strategy for evaluating pediatric PE in children who fail the PERC-Peds rule.
Specifically, the sequential strategy safely excluded PE in 54.7% of enrolled children and in 69% of children with D-dimer ordered. The false-negative rate was 0.9% (95% CI 0.6–1.4%), while the estimated reduction in CTPA use was ~18.5%.
What did the BEEPER study do well?
The trial successfully challenged the historical assumption that paediatric PE is rare whilst proving that using structured clinical prediction rules rather than immediate advanced imaging may safely minimise unnecessary CTPAs without missing critical diagnoses.
Limitations of the Study
The protocol relied on subjective clinical gestalt, which may cause baseline variability amongst providers.
As the trial was conducted within specialised paediatric emergency networks, the findings may not generalise to resource-constrained community hospitals.
Statistically, the small absolute number of positive cases may limit the power needed to calibrate the diagnostic criteria across all developmental age brackets.
Finally, using 45-day follow-ups may introduce verification bias, potentially leaving small or self-resolving emboli undetected.
CASP Checklist. How good was the paper?
Did the study address a clearly focused issue?
Yes.
Was there a comparison with an appropriate reference standard?
Yes. The study compared the PERC-Peds rule against a solid reference standard: definitive imaging for high-risk patients and a 45-day clinical follow-up for all others.
Did all patients get the diagnostic test and reference standard?
No. Giving every child invasive imaging is unethical. Instead, the study safely used a composite reference standard.
Could the results of the test have been influenced by the results of the reference standard?
No. As the PERC-Peds criteria were scored before advanced imaging was performed or the 45-day follow-up had even begun, it was chronologically impossible for the final diagnosis to influence the initial test results.
Was the outcome accurately measured to minimise bias?
Yes, but with expert nuance. True-positive outcomes were confirmed by CT/VQ scanning or ultrasound.
There was a minor risk of missing small, subclinical clots, as the outcome for negative patients relied heavily on clinical follow-up, as it is ethically impossible to perform CT scans on asymptomatic, low-risk children.
Have the authors identified all important confounding factors?
Yes. Extensive data on baseline comorbidities known to skew paediatric VTE were considered in the epidemiological profile.
Is the disease status of the tested population clearly described?
Yes. The study clearly described the population with suspected pulmonary embolism across 21 Emergency Departments.
What are the results of this study?
The PERC-peds rule, combined with selective D-dimer testing, achieved a sensitivity of 99.6%, keeping the missed PE rate well below the strict safety threshold of <1.5%.
How precise were the results?
Given the high level of statistical precision through the high enrolment rate, tight confidence intervals and negative predictive value it gives clinicians strong mathematical backing when making the decision of withholding imaging in a low-risk child.
What are the consequences of these results?
By implementing the BEEPER framework, there is a substantial reduction in unnecessary radiation and contrast risks while also improving emergency department length of stay and reducing direct cost.
Can the results be applied to the local population?
Yes. Although the study was done in the USA, clinical findings would transfer to UK paediatric patients, with the caveat being safe UK implementation relying heavily on senior emergency medicine oversight and consistent access to high-sensitivity D-Dimer testing.
The bottom line. What should I do with my patient?
A negative PERC-Peds assessment, when combined with low clinical suspicion, provides the reassurance needed to avoid unnecessary CTPA.
The BEEPER trial sets the framework for a standardised sequential pediatric PE evaluation approach, in which clinicians could use PERC-Peds, followed by D-dimer testing when required, reserving imaging for children at higher risk.
It also allows us to safely look a parent in the eye and say, “We can safely rule out a blood clot in the lungs today without exposing your child to radiation.“
A note from the authors (Jeffrey A. Kline)
We hope that BEEPER has laid the groundwork for clinical criteria that can rule out pulmonary embolism safely without radiation in children, and at the same time give clinicians a framework to help them know when to consider pulmonary embolism in their active differential diagnosis.
Future work is needed to study PERC–PEDS in a management study.
References
Jinks S, Arana A. Venous thromboembolism in paediatrics BJA Education, 2019; 19, 305-312
Zaidi AU, Hutchins KK, Rajpurkar M. Pulmonary Embolism in Children. Front Pediatr. 2017 Aug 10;5:170. doi: 10.3389/fped.2017.00170. PMID: 28848725; PMCID: PMC5554122.
National Institute for Health and Care Excellence. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing [Internet]. London: NICE; 2020 Mar [updated 2020 Mar; cited 2026 Jul 19]. (Clinical guideline [NG158])
Liu J, Ni X, Zeng L, et al. Epidemiological characteristics of pulmonary thromboembolism in children: a systematic review and meta-analysis BMJ Open 2026;16:e104471. doi: 10.1136/bmjopen-2025-104471
Mercurio L, Corwin D, Kaplan R, Ellison AM, Casper TC, Kuppermann N, Kline JA. Bedside exclusion of pulmonary embolism in children without radiation (BEEPER): a national study of the Pediatric Emergency Care Applied Research Network-Study protocol. Res Pract Thromb Haemost. 2023 Jan 14;7(2):100046. doi:10.1016/j.rpth.2023.100046. PMID: 36865906; PMCID: PMC9971278.
Denise Bastas, Leonardo R. Brandão, Jennifer Vincelli, David Wilson, Lucy Perrem, Vitor Guerra, Gina Wong, Robert F. Bentley, Soumitra Tole, Jane E. Schneiderman, Nour Amiri, Suzan Williams, M. Laura Avila; Long-term outcomes of pulmonary embolism in children and adolescents. Blood 2024; 143 (7): 631–640. doi: https://doi.org/10.1182/blood.2023021953
