Brief Resolved Unexplained Events (BRUEs): New Name, Similar Challenges

Brief resolved unexplained events (BRUEs) are a common pediatric condition characterized by a change in color (cyanosis or pallor), breathing pattern, tone, or level of responsiveness in a child <1 year of age. For parents and caregivers, these events are frightening and warrant trying to identify an underlying cause.¹  For pediatricians, BRUEs are a clinical challenge because the causes and long-term outcomes are not well understood despite decades of research. Despite these challenges and the limited evidence base, the American Academy of Pediatrics (AAP) published a clinical practice guideline (CPG) in 2016 to narrow the definition of BRUE and provide recommendations on management.²  Beyond retiring the term apparent life-threatening event for BRUE, the CPG outlined a revised risk stratification in which lower risk infants were defined as those >60 days of age, gestational age >32 weeks and postconceptional age >45 weeks, with no previous BRUEs, event duration <1 minute, not requiring cardiopulmonary resuscitation, and with no concerning historical features or physical examination findings.² 

In this edition of Hospital Pediatrics, Patra et al³  evaluate the impact of this new CPG by looking at management and health system outcomes before and after it was published. Patra et al³  used the Pediatric Health Information Systems database to analyze admission rates, diagnostic testing, treatment, cost, length of stay, and revisits in patients with BRUE before the guideline compared with after the guideline. Using an interrupted time series approach, they found an early decrease in 12 diagnostic tests that the CPG strongly recommends against. The magnitude of this reduction was variable, with some showing larger decreases (eg, chest radiography from 49% to 35%, complete blood count from 45% to 31%) and others showing smaller decreases (eg, neuroimaging from 13% to 10%). The only test that is recommended, electrocardiogram, increased, although the absolute magnitude was small (36% to 39%), and use was still low. There were also health system impacts, with significant reductions observed in hospital admissions, medications use, costs, and length of stay but no change in revisit rates.

This study adds to the growing body of literature comparing patient care and resource stewardship before and after publishing of the BRUE CPG,⁴  suggesting adherence to the new guideline. Furthermore, this study used a larger date range with a more inclusive, validated, patient identification methodology compared with existing studies.⁵  Although there was a decline in diagnostic testing and treatment resource use, several of the trends were already decreasing before the CPG was released. There was likely broader recognition of the limited utility of extensive and potentially invasive testing for children with a BRUE.

Yet, a key clinical question remains at the heart of each encounter with a patient with BRUE: what is the likelihood that the child has a serious underlying illness? This uncertainty plays a significant role in provider decisions and can ultimately determine diagnostic test usage, hospital admission, and cost. The second article in this edition, building on knowledge of the health system impact of the widely adopted CPG, uses data from the BRUE Research and Quality Improvement Network to derive and validate a clinical decision rule for predicting the risk of a serious underlying diagnosis or event recurrence and compares it with the AAP guideline.⁶ 

The study included 3283 infants, of which 4.6% (150) were diagnosed with a serious underlying illness. Serious illness was defined as a condition that could explain the presenting events and requiring timely diagnosis, in which a delay could potentially cause significant morbidity or mortality. The most common serious illnesses were seizures requiring treatment with antiepileptic drugs (29%), airway abnormalities treated with surgery (13%), and severe dysphagia or gastroesophageal reflux disease treated with nasogastric tube feeding (11%), reflecting the wide variety of underlying diagnoses. The sensitivity of the AAP guideline criteria for a serious diagnosis was 95.3%, whereas the specificity was only 8.6%. The newly derived model, which included age, previous events, and abnormal medical history, had a similar area under the curve as the AAP guideline for predicting a serious underlying diagnosis (0.61 vs 0.52; P = .10) but was superior for predicting event recurrence (0.54 vs 0.68; P < .001). The authors also found that in contrast to the AAP criteria, patients >60 days old were more likely to have a serious underlying diagnosis.

The study by Nama et al⁶  helps to address evidence gaps in the AAP guideline by focusing on the higher risk population and the risk for a serious underlying illness. The authors also developed a shared decision-making tool that will be publicly available to help clinicians and families make decisions. This is particularly useful in a condition such as BRUE, which can be ambiguous and clouded by diagnostic uncertainty. The tool’s ability to quantify the risk of serious underlying illness may either emphasize the need for closer outpatient follow-up or provide reassurance to a worried caregiver who has witnessed a frightening event.

Although these 2 studies help to address knowledge gaps in BRUE, they are not without caveats. Nama et al⁶  were able to improve on the accuracy of the AAP guideline for event recurrence, yet the actual performance of the model is still suboptimal. Unfortunately, because of the Classification and Regression Tree model used, the authors were unable to provide comparable sensitivity and specificity values to the AAP guideline, so it is difficult to compare other than looking at area under the curve. The decision-making tool will help provide these values using individual patient variables, but rather than being viewed as definitive, it should be used in conjunction with open discussion between clinicians and caregivers.

Another important limitation in Nama et al⁶  is the absence of risk stratification among the study subjects.²  Because of limitations in the Pediatric Health Information Systems, the authors were unable to differentiate between lower risk and higher risk patients, and yet the AAP guideline only applies to those deemed lower risk. Several studies have shown that a significant majority of infants presenting to the emergency department with BRUE will meet the AAP higher risk criteria, ranging from 87% to 91.8%.⁷  Therefore, further study is required to better understand the true impact of the guideline on its intended patient population.