Brief Resolved Unexplained Event (BRUE)


Article Author:
Noah Kondamudi


Article Editor:
Mumtaz Virji


Editors In Chief:
David Wood
Andrew Wilt
Hajira Basit


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
6/4/2019 4:25:58 PM

Introduction

The American Academy of Pediatrics published a clinical practice guideline in 2016 recommending replacing the term apparent life-threatening event (ALTE) with a new term named brief resolved unexplained event (BRUE)[1][2]. An apparent life-threatening event was defined as any event that was frightening to the observer and consisted of a combination of apnea, color change, muscle tone change, and choking, or gagging. An apparent life-threatening event[3], which itself replaced the term near-miss sudden infant death syndrome (SIDS) in 1986[4], was regarded to be too imprecise for clinical practice and research due to its subjective and non-specific symptoms and causation by a wide range of disorders. Furthermore, this definition relied on the subjective report of the observer rather than on pathophysiology. The new label brief resolved unexplained event serves to remove the “life-threatening” label and better reflect the transient nature of the event and lack of a clear cause. 

The definition of a brief resolved unexplained event is an observed event occurring in an infant younger than one year of age where the observer reports a sudden, brief, yet resolved episode of one or more of the following:

  • Cyanosis or pallor
  • Absent, decreased, or irregular breathing
  • Marked change in tone (hyper- or hypotonia)
  • Altered level of responsiveness.

The diagnosis of brief resolved unexplained event can only be made when there is no explanation for a qualifying event after an appropriate history and physical examination.

Review of previous apparent life-threatening event literature reveals that a small subset of infants with a diagnosis compatible with a brief resolved unexplained event may have a serious underlying disease or are prone to recurrent episodes.

High-risk infants are those younger than two months of age, those with a history of prematurity (higher in less than 32 weeks gestation), and those with more than one event. Low-risk infants were those that are:

  • Age older than 60 days
  • Gestational age 32 weeks or older
  • Postconceptional age greater than or equal to 45 weeks
  • First brief resolved unexplained event (no previous brief resolved unexplained event ever and not occurring in clusters)
  • Event lasting less than one minute
  • No CPR required by the trained medical provider
  • No concerning historical features or physical examination findings.

Patients who do not meet criteria as low risk by default are considered high risk.

Etiology

Implicit in the definition of brief resolved unexplained event is the word unexplained, indicating that there is no underlying cause. Nevertheless, infants in the high-risk category may have an underlying cause similar to those previously described in the apparent life-threatening event literature. These include gastroesophageal reflux, seizures, bronchiolitis, pertussis and child abuse[5]. Other less frequent causes are inborn errors of metabolism, cardiac arrhythmias, increased intracranial pressure, toxic ingestions and syndromic conditions, especially those involving craniofacial anomalies.

Epidemiology

Brief resolved unexplained event has been described only in 2016, and thus there are no reports describing the epidemiology. An apparent life-threatening event includes a subset of brief resolved unexplained events accounted for approximately 0.6% to 0.8% of all emergency department (ED) visits[3] and 0.6 to 2.6% per 1000 live births. One study inLombardy region, Italy[6] had a cululative incidence of 4.1 cases per 1000 livebirths. 

Pathophysiology

As brief resolved unexplained event is an unexplained event, pathophysiology of these events is unknown. However, the possible role of abnormalities in the swallowing mechanisms, in laryngospasm, in gastroesophageal reflux, and in autonomic function, are yet to be elucidated.

History and Physical

History and physical exam are essential to categorize the event as brief resolved unexplained event or to assign an alternate diagnosis. It is useful to ascertain the history with the clear focus on the circumstances before, during, and after the event. Features to be clarified before the event include the location of the event (home/daycare), whether the infant was awake or asleep, infant position (supine/prone, other), and activity (feeding, the presence of anything in the mouth, vomit/spit up). A thorough description of the event including if the infant was active or quiet, responsive or unresponsive, breathing, not breathing, or struggling to breathe, choking or gagging, appeared limp, rigid, or seizing, seemed distressed or alarmed, and change in skin or lip color (red, pale, blue). After the event, determine the approximate duration of event, abrupt or gradual termination, spontaneous termination or any interventions used (picking up, rubbing, CPR), behavior before return to normal (quiet, startled, fussy, or crying). Other useful information about recent illness, associated symptoms, history of illnesses especially apparent life-threatening event/brief resolved unexplained event, antenatal/perinatal history including gestational age, developmental delays, family history of early deaths especially, SIDS/apparent life-threatening event or presence of cardiac arrhythmias. Social history should focus on identifying the availability of social support systems and access to resources.

Infants presenting with brief resolved unexplained event are well and appear to have normal vital signs and physical exam findings. However, a thorough physical exam is required to identify those with high-risk brief resolved unexplained event or find the trigger to an alternate diagnosis.

Evaluation

Infants with a low-risk brief resolved unexplained event do not require any testing. A brief period of observation (one to four hours) with continuous pulse oximetry is adequate. The American Academy of Pediatrics does not offer any guidance for infants with high-risk brief resolved unexplained event; the common sense approach is to perform relevant tests based on specific areas of concern identified in the history or physical exam. Performing a 12-lead EKG can be considered as the benefit of identifying channelopathies that lead to sudden death and outweigh any harm. Testing for pertussis may be useful in the at-risk populations (suggestive symptoms, unimmunized patients). Other tests such as complete blood count, electrolytes, blood glucose, lactic acid, bicarbonate levels, blood gas, blood cultures, urine analysis, imaging, electroencephalogram (EEG), pH probe, and polysomnography[7] are not routinely recommended.  

Treatment / Management

The key component of management is to educate caregivers about the condition, ensure close follow-up after discharge, and provide resources for training in cardiopulmonary resuscitation. Admission for cardiorespiratory monitoring is not routinely indicated. There is no role for medications, tests, specialist consultations, or home cardiorespiratory monitoring. Infants that are not low-risk should be managed based on the physiological status and abnormalities identified in history and physical exam. Admission criteria[8] recommended for patients that were previosuly described as ALTE included patients that required CPR and had another clear reason for hospitalization, had more than one ALTE event within a 24 hour period and if there was associated significant underlying disease associated. AAP guideline does not make any recommendations for management of high risk BRUE.

Differential Diagnosis

Several conditions can present with a brief apenic event, but would not be categorized as BRUE if they fit into another definable diagnosis. Both upper and lower respiratory infections (e.g. Bronchiolitis, pertussis, pneumonia) can cause apneic event. Other conditions to consider include sepsis, meningitis, gastroesophageal reflux, seizures, infant botulism, prolonged QT syndrome,metabolic disorders, and child abuse.

Prognosis

As BRUE is anew entilty, there is paucity of data regarding prognosis. Previously studies prognosis for ALTE may offer some insight at least for patients with high risk BRUE. One year mortality after ALTE in one study was <1%[9]. The readmission rate within 30 days for an ALTE visit was 2.5%[10]

Complications

No known complications

Pearls and Other Issues

A few patients can present with brief resolved unexplained events like episodes that may not fit the definition. It is prudent that these infants be evaluated diligently and even be considered for hospitalization to facilitate a period of observation. Shared decision-making with caregivers should be part of the overall management strategy, especially in the face of a seemingly uncertain situation.

Enhancing Healthcare Team Outcomes

BRUE is best managed by a multidisciplinary team that includes a pediatric nurse. The key component of management is to educate caregivers about the condition, ensure close follow-up after discharge, and provide resources for training in cardiopulmonary resuscitation. Admission for cardiorespiratory monitoring is not routinely indicated. There is no role for medications, tests, specialist consultations, or home cardiorespiratory monitoring. Infants that are not low-risk should be managed based on the physiological status and abnormalities identified in history and physical exam.

 However, in some high-risk children, one should undertake relevant studies to ensure that there is no sinister cause of BRUE (Eg meningitis).


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Brief Resolved Unexplained Event (BRUE) - Questions

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What is the most common cause of a brief resolved unexplained event in infants?



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Which of the following findings is not included in an apparent life-threatening event (ALTE)?



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A 4-month-old female is brought to the emergency department after stopping breathing for about 30 seconds. The mother reports her lips became blue and she didn't resume breathing until she blew in her face. The patient had no symptoms before the event. She is breastfed and has had all the immunizations. On physical examination, the patient is irritable but consolable, alert with no apparent abnormalities. Vital signs: heart rate 138/min, respiratory rate 29/min, temperature 98 F, blood pressure is difficult to obtain, and oxygen saturation 97% in room air. What is the next step in the evaluation of this patient?



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A 4-month-old female is brought to the emergency department after stopping breathing for about 30 seconds. The mother reports her lips became blue and she didn't resume breathing until she blew in her face. The patient had no symptoms before the event. She is breastfed and has had all immunizations. On exam, the patient is irritable and alert. Oxygen saturation is 97% on room air. The rest of the exam is normal. Which of the following is appropriate management?



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A 6-month-old child is admitted with an apparent life-threatening event, but evaluation including history, physical, CT of the head, electrolytes, EEG, serum glucose are all normal. Select appropriate management.



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A 6-month-old infant presents with a period of apnea lasting 20 seconds, lips and mouth turned blue, became limp and caught his breath when his mother blew air into his mouth. History is remarkable for premature birth at 28 weeks gestation and episodes of apnea in the neonatal period, which was treated with Caffeine. The infant has been doing well since discharge but developed slight runny nose and cough two days ago. The vital sign includes a heart rate of 155b/min, respiratory rate 49/min, temperature 100.9F (38.3C), and pulse oximetry 92% in room air. Physical exam reveals nasal congestion with slight flaring of he ale nasi and subcostal retractions. There is good air entry bilaterally with an occasional wheeze. He appears alert, pink, and active, and the rest of the physical examination is unremarkable. What is the next step in the management of this patient?



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Which of the following historical features are least compatible with a diagnosis of BRUE (formerly ALTE)?



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Which of the following tests are recommended when treating an infant with a brief resolved unexplained events (BRUE)?



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Which of the following is not a component of the brief resolved unexplained events definition?



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Which of the following is not a cause of central apnea in infants?



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Which of the following tests are not recommended during evaluation of a child presenting with low-risk brief resolved unexplained event (BRUE)?



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A 5-month-old infant is brought in by the mother with the chief complaint that the infant stopped breathing and had to be vigorously tapped on his back before resuming his breathing. The episode lasted approximately 2 minutes, and she noted that his lips turned blue during the episode. Mother denies any seizure-like activity, and the child was well when she left to work earlier in the day. Mother works in a daycare center, and the infant is cared for by her boyfriend along with her two other children aged 2 and 4 years. In the emergency department, the child appears somewhat limp and is less active. Mother reports that she was abusing opiates during her pregnancy but otherwise was unremarkable. The infant was born at full term with no perinatal complications. Vital signs show a pulse of 98/min, respiratory rate 34/min, temperature 99.2 F, and oxygen saturation is 98% on room air. His physical examination is remarkable for decreased tone with normal reflexes but otherwise normal. What is the best initial step in the management of this patient?



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A 7-month-old infant is brought in by EMS with a history of cessation of breathing while being fed. When they arrived at the scene, the mother was in tears that her child turned blue with no breathing and became very limp for about 45 seconds after which he took a big gasp and became pink again and began to cry. EMS report that no immediate resuscitation was done. During transport, EMS noted another episode where the infant became limp and apneic for 30 seconds and resumed respirations spontaneously. On arrival at the emergency department, the infant appears pink and is crying vigorously. Vitals reveal a pulse of 130/min, respiratory rate 34/min, temperature 99.1 F, and oxygen saturation is 98% on room air. Physical exam reveals an active child in no distress and normal physical findings. Which of the following would most likely preclude him from being categorized as 'low-risk BRUE'?



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Brief Resolved Unexplained Event (BRUE) - References

References

Tieder JS,Bonkowsky JL,Etzel RA,Franklin WH,Gremse DA,Herman B,Katz ES,Krilov LR,Merritt JL 2nd,Norlin C,Percelay J,Sapién RE,Shiffman RN,Smith MB, Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants. Pediatrics. 2016 May;     [PubMed]
Arane K,Claudius I,Goldman RD, Brief resolved unexplained event: New diagnosis in infants. Canadian family physician Medecin de famille canadien. 2017 Jan;     [PubMed]
Fu LY,Moon RY, Apparent life-threatening events: an update. Pediatrics in review. 2012 Aug;     [PubMed]
Vigo A,Balagna R,Brazzi L,Costagliola G,Gregoretti C,Lupica MM,Noce S, Apparent Life-Threatening Events: Helping Infants Help Themselves. Pediatric emergency care. 2018 Aug;     [PubMed]
Radovanovic T,Spasojevic S,Stojanovic V,Doronjski A, Etiology and Outcome of Severe Apparent Life-Threatening Events in Infants. Pediatric emergency care. 2018 Oct;     [PubMed]
Monti MC,Borrelli P,Nosetti L,Tajè S,Perotti M,Bonarrigo D,Stramba Badiale M,Montomoli C, Incidence of apparent life-threatening events and post-neonatal risk factors. Acta paediatrica (Oslo, Norway : 1992). 2017 Feb;     [PubMed]
Tieder JS,Altman RL,Bonkowsky JL,Brand DA,Claudius I,Cunningham DJ,DeWolfe C,Percelay JM,Pitetti RD,Smith MB, Management of apparent life-threatening events in infants: a systematic review. The Journal of pediatrics. 2013 Jul;     [PubMed]
Aminiahidashti H, Infantile Apparent Life-Threatening Events, an Educational Review. Emergency (Tehran, Iran). 2015 Winter;     [PubMed]
Parker K,Pitetti R, Mortality and child abuse in children presenting with apparent life-threatening events. Pediatric emergency care. 2011 Jul;     [PubMed]
Tieder JS,Cowan CA,Garrison MM,Christakis DA, Variation in inpatient resource utilization and management of apparent life-threatening events. The Journal of pediatrics. 2008 May;     [PubMed]

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