Small Talk – Finding the Right Clues to Manage BRUEs

Welcome back to Small Talk; a new monthly section from emDOCs.  Every first Wednesday of the month we will release high yield PEM content written by PEM talent from around the country.  We hope you enjoy these reviews. Comments, questions, accolades or concerns: feel free to reach out to Joe Ravera, MD (pemgemspod@gmail.com).


Author: Raymen Rammy Assaf, MD, MPH, MA (Pediatric Emergency Medicine Fellow, Harbor UCLA Medical Center) // Reviewed by: Joe Ravera, MD (@pemuvm1, Director of Pediatric Emergency Medicine, UVM Medical Center, Assistant Professor of Surgery, UVM College of Medicine); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)


Case

Paramedics bring in a 2-week-old girl weighing 3.8 kg after a 30-second-long episode of facial cyanosis, loss of tone, and decreased responsiveness. Her mother states she looked like she was struggling to breathe during that entire time. She had breastfed 2 ounces and then laid down supine for a nap about an hour prior. The baby is acting normally now according to her mother. She is comfortable, with soft and flat fontanelles, no increased work of breathing, no cardiac murmur with equal pulses in upper and lower extremities, abdomen soft with no masses, normal strength and tone, no obvious signs of trauma and no dysmorphic features. The patient’s mother anxiously asks “Is my baby going to be ok?”


Background

Clinical practice guidelines on the brief resolved unexplained event (BRUE) were introduced by the American Academy of Pediatrics (AAP) in 2016 which defined it as an event occurring in an infant younger than 12 months with one or more of the following features:1

1) Cyanosis or pallor

2) Absent, decreased, or irregular breathing

3) Marked change in tone (hyper- or hypotonia)

4) Altered level of responsiveness

Those at lower risk for a repeat event or serious underlying condition must meet all of the following criteria:1

  • Age greater than 60 days
  • Absent prematurity: gestational age ≥ 32 weeks and post-conceptual age ≥ 45 weeks
  • First BRUE (no previous BRUE ever and no repeat events)
  • Duration of event < 1 minute
  • No CPR required by trained medical provider
  • No concerning historical features (e.g. sudden death in first-degree relative)
  • No concerning physical examination findings (e.g. unexplained bruising)

The BRUE Effect

BRUE did not simply replace the former term apparent life-threatening event (ALTE) – which itself had supplanted the term “near-miss sudden infant death syndrome (SIDS)” in 1986 – but offered a more precise definition of the transient and often benign event characteristics using clear criteria that help guide management.1 Understanding the history of the nomenclature and its evolution is important as the term “life-threatening” was removed since a diagnosis of ALTE was never found to confer mortality risk.1-4 In multiple retrospective reviews, only a minority of patients with ALTE met BRUE criteria.2,5,6 The effect of this more standardized approach to management has translated into a significant reduction of diagnostic/invasive testing, ED length of stay, and admission rate of infants in both the 0 to 60 day and 61 to 365 day age group with no change in clinical outcome including readmissions or repeat ED visits.7,8


BRUE Documentation Do’s and Don’ts

A BRUE is, by definition, unexplained after careful history and physical exam. For instance, in a patient with findings such as reflux (20 to 54% of patients), URI (8%), or seizure (4 to 7%), a diagnosis of BRUE should not be made and the patient be managed according to the presumed etiology.9 Consistent with guidelines, a thorough history and physical exam are the most important components of the patient assessment.1 The clinician should be clear in their documentation of differentiating a patient with lower risk versus higher risk BRUE, as this will guide evaluation and management. It is critical to obtain a detailed recount of the event from the caregiver and/or transporting personnel, with description of the patient’s state immediately before, during, at the conclusion of, and after the event.9 Complete history-taking includes preceding or concurrent illness and thorough medical, family, social, and environmental history.9 A documented physical exam should note any vital sign abnormality, growth curve irregularity, altered infant responsiveness, craniofacial anomaly or dysmorphic features, respiratory impediment, abnormal auscultation findings, palpable masses, genital anomaly, complete neurologic exam (strength, sensation, tone), and skin exam (bruising, rash, swelling or any subtle signs of child maltreatment).1 If there is any noted abnormality and/or concern for possible abuse, the event is not categorized as lower risk and requires further detailed investigation.9


Lower Risk BRUE

Apart from being pragmatic, fulfillment of the lower risk BRUE criteria has proven to be a reliable indicator of excellent prognosis based on patient long-term follow-up.10 These patients have decreased overall risk of adverse outcomes and do not warrant hospitalization nor broad clinical evaluation, assuming the clinician has screened for social risk factors including child abuse.9 Patients may undergo a screening 12-lead ECG and be observed on continuous pulse oximetry for a short (1 to 4 hour) period of time in the emergency department (ED). Current guidelines strongly recommend against obtaining any bloodwork (e.g. glucose, CBC, blood gas, blood culture, urine studies, viral respiratory tests) or imaging (e.g. chest XR, head CT).


Higher Risk BRUE

A myriad of causes from nearly every organ system may lead to presentation of a BRUE. For those that do not meet lower risk criteria, there is at this time a general lack of evidence to guide evaluation.11 Therefore, the clinician, on a case-by-case basis among these patients, should consider wide differential diagnoses and pursue workup based on an index of clinical suspicion after reviewing pertinent history and clinical findings, all in the context of shared clinical decision making with the caregiver.9 While clinicians should err on the side of caution, routine hospitalization may not be warranted for all of the higher risk patients.9,11 Initial evaluation and management to identify a condition with potentially serious adverse outcomes may include:11

  • Continuous pulse oximetry monitoring for at least 4 hours;
  • Consultation with social worker (or other health care worker with similar experience and skills);
  • Bedside feeding evaluation (by a feeding therapist, if available);
  • Electrocardiogram to be read by a pediatric cardiologist or electrophysiologist;
  • Rapid viral respiratory panel testing;
  • Rapid pertussis polymerase chain reaction in endemic areas, during regional outbreaks, or in underimmunized patients;
  • Complete blood count (CBC) with differential;
  • Chest and/or abdominal radiographic imaging;
  • Blood glucose, bicarbonate or venous blood gas, and lactate; and
  • If concerned for child maltreatment, consultation with a child abuse expert, head imaging with computed tomography (CT) or MRI, and skeletal survey

 

If no cause is identified, a secondary tier of evaluations is performed either inpatient or outpatient and may include the following:11

  • Specialty consultation with a gastroenterologist, otolaryngologist, pulmonologist or sleep expert, child abuse expert, neurologist, cardiologist, and/or biochemical geneticist;
  • Videofluoroscopic swallowing study (VFSS) for “silent” oropharyngeal dysphagia not seen in bedside evaluation;
  • Continuous prolonged oximetry to characterize recurring events;
  • Comprehensive polysomnography (PSG) to characterize and quantify central versus obstructive apnea;
  • Prolonged (≥ 12–24 hours) EEG;
  • Blood sodium, potassium, chloride, blood urea nitrogen, creatinine, calcium, and ammonia for metabolic disturbance;
  • Upper gastrointestinal series (UGI);
  • Esophageal multichannel intraluminal impedance–pH monitoring (MII-pH);
  • Esophagogastroduodenoscopy with biopsy;
  • Echocardiogram; and
  • Urine organic acids, plasma amino acids, or plasma acylcarnitines

 

An individualized, family-centered multidisciplinary approach to management of the higher risk patient with BRUE is advocated. Below is a table of specific time-sensitive diagnoses arranged by organ system, which if missed, may have serious impact on patient morbidity or mortality:11


Discussing a BRUE with parents

BRUE remains an imperfect label. It is less of a diagnosis and more a constellation of symptoms.12 Parents of infants with BRUE – specifically those discharged who compose the majority – have expressed confusion, anxiety, unease, and fear around the unexplained nature BRUE, but more so the possibility of its unexpected recurrence.12 Shared medical decision making with the family should guide evaluation, and the clinician should ensure timely follow-up with the infant’s pediatrician.9 In communicating with the caregiver at discharge, it is recommended that clinicians shift away focus “from what is unexplained to what is known”, addressing the benign nature of lower risk BRUE and extremely low likelihood of recurrence or serious underlying condition.9,12 CPR training resources should also be offered. Of course, should an etiology such as reflux be identified, the patient should not be diagnosed with BRUE and the family should be counseled on “reflux precautions” including appropriately-sized feeds (e.g. avoid overfeeding), proper burping, and keeping the child upright immediately after a feed, as well as the commonality of gastroesophageal reflux in infants.


Case Continued

After a thorough history and exam, no apparent etiology of the BRUE is discovered. The neonate is appropriately categorized as a higher risk patient (based on age <60 days) and the decision is made to obtain basic labs, an ECG, and chest XR in the ED with admission to the general pediatric inpatient team. No repeat events are noted in the ED. Together with shared medical decision making involving the caregiver, the ED clinician discusses the lack of abnormal findings on initial workup and the importance of inpatient monitoring.


Pearls and Pitfalls

  • Since 2016, a defined BRUE criteria among infants has had a profound impact on reducing invasive diagnostic testing, ED length of stay, and admission rate without negatively impacting any clinical outcomes.
  • A detailed and complete clinical history and physical exam remain the most important aspects of early evaluation. A BRUE should be diagnosed only if there remains no explanation for the event. If there are any concerning features discovered, the patient is not lower risk and warrants further workup.
  • Infants with lower risk BRUE exhibit a transient and benign event that has an extremely low risk of recurrence and/or underlying serious condition. In the ED, these patients may undergo a screening 12-lead ECG and/or observation of 1 to 4 hours, but no other interventions are warranted.
  • Clinical guidelines among higher risk BRUE remain less clear, and thus the ED clinician should consider wide differential diagnoses, pursuing an initial workup based on clinical index of suspicion while erring on the side of caution.
  • Whether lower or higher risk criteria are met, it is essential the clinician clearly communicate their findings and appropriately counsel caregivers, while remaining empathic to their concerns.

References/Further Reading

  1. Tieder JS, Bonkowsky JL, Etzel RA, et al. Brief unresolved unexplained events (formerly apparent life-threatening events) and evaluation of lower-risk infants. Pediatrics. 2016;137(5):e20160590.
  2. Gerber NL, Fawcett KJ, Weber EG, et al. Brief resolved unexplained event: not just a new name for apparent life-threatening event. Pediatric Emergency Care. 2020. 10.1097/pec.0000000000002069
  3. Mittal MK, Sun G, Baren JM. A clinical decision rule to identify infants with apparent life-threatening event who can be safely discharged from the emergency department. Pediatric Emergency Care. 2012;28(7):599–605.
  4. Kaji AH, Claudius I, Santillanes G, et al. Apparent life-threatening event: multicenter prospective cohort study to develop a clinical decision rule for admission to the hospital. Annals of Emergency Medicine. 2013;61(4):379–387.
  5. Ramgopal S, Soung J, Pitetti R. Brief resolved unexplained events: analysis of an apparent life threatening event database. Academic Pediatrics. 2019;19(8):963-968.
  6. Meyer JS, Stensland EG, Murzycki J, et al. Retrospective application of BRUE criteria to patients presenting with ALTE. Hospital Pediatrics. 2018;8:740–745.
  7. Ramgopal S, Noorbakhsh K, Callaway C, et al. Changes in the management of children with brief resolved unexplained events (BRUEs). Pediatrics. 2019;144(4):e20190375.
  8. Sethi A, Baxi K, Cheng D, et al. Impact of guidelines regarding brief resolved unexplained events on care of patients in a pediatric emergency department. Pediatric Emergency Care. 2020. 10.1097/PEC.0000000000002081.
  9. Behnam-Terneus M, Clemente M. SIDS, BRUE, and Safe Sleep Guidelines. Pediatrics in Review. 2019;40(9):443-455.
  10. Ari A, Atias Y, Amir J. Long-term follow-up of infants after a brief resolved unexplained event-related hospitalization. Pediatric Emergency Care. 2019;35(11):765-768.
  11. Merritt JL, Quinonez RA, Bonkowsky JL, et al. A framework for evaluation of the higher-risk infant after a brief resolved unexplained event. Pediatrics. 2019;144(2):e20184101.
  12. DeLaroche AM, Mittal MK. But what was “it”? Talking to parents about BRUE. Hospital Pediatrics. 2019;9(7):566-568.

 

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