Brief Resolved Unexplained Event (BRUE)

Case

A previously healthy 5-week old boy who was born at term is brought to the emergency department. His mother reports that she had placed him on his side with a support pillow after breast-feeding him before she went to take a shower. 

                                                        
Upon returning to check on him, she found him in prone position, with his nose and mouth in the mattress, “struggling” to breathe; his face was red. The mother thought he looked “sleepy.”  She picked him up, noting his tone was somewhat decreased; she ran his head under cold water with an increase in respiration but he still seemed sleepy
                                             
The mother watched him for an hour and breast-fed him. After discussing it with her son’s pediatrician, she brought him to the emergency department (ED)1

The quoted excerpt above (and those following) are from a fantastic recent article by our very own Dr. Alison Chu (Neonatology Fellow) and Dr. Joe Hageman, and it is illustrative of the type of description parents often provide in this situation.

Although a familiar diagnosis for the practicing pediatrician and trainee, BRUEs can be incredibly distressing to families as their name alludes.  BRUEs require a very careful history and examination, as well as honest discussion and guidance from all involved.

The following seeks to provide a framework for evaluating BRUEs, as well as guidance on what workup may or may not be necessary.

Definition

BRUE--formerly Apparently Life Threatening Event (ALTE)--is not a specific diagnosis, but a description of the acute event.

  • "an event occuring in an infant <1 year of age when the observer reports a sudden, brief, and now resolved episode of [more than one] of the following:
    • Cyanosis or pallor
    • Absent, decreased, or irregular breathing
    • Marked change in tone (hyper- or hypotonia)
    • Altered level of responsiveness

...when there [is] no explanation for a qualifying even after...an appropriate history and physical examination"

Differences from ALTE:

  • Establishes a set age limit for patients (less than a year old)
  • BRUE only occurs if there are no other explanation for the precipitating event
  • The diagnosis of BRUE relies on a clinician's characterization of the features of the event, rather than a concerned caregiver's subjective assessment of whether an event was "life-threatening"
  • Altered responsiveness is added

Risk Factors

  • Age under 60 days
  • Birth below 32 weeks' gestation and corrected gestational age less than 45 weeks
  • Requirement for CPR by a trained medical professional
  • Even lasting for more than a minute
  • Prior presentations of BRUE

Etiologies to Consider

  1. Normal variation. No significant color changes or bradycardia.
    • Short periods of apnea
    • Periodic breathing
    • Minor airway obstruction - Increased because of floppy airways in neonates and infants
  2. Infections - RSV, Pertussis, Respiratory & CNS infections
  3. Drugs
  4. Gastroesophageal reflux - may be diagnosed and not the cause of the ALTE
  5. Seizures
  6. Cardiac - congenital malformations or arrhythmia
  7. ENT abnormalities - such as laryngeal or tracheal abnormalities
  8. Metabolic conditions - may be triggered by fasting and may be accompanied by symptoms of hypotonia, lethargy, or vomiting.
  9. Non-accidental trauma
  10. Munchhausen syndrome
  11. Idiopathic - majority of cases.

Evaluation

The following if a guide of elements that should be considered, as well as what further evaluation may be necessary dependant on consideration of the history and physical exam. 

  1. History

  • Duration of spell and resuscitative measures used
  • Was the infant awake or asleep?
  • Relationship to feeds and were there any noises.
  • Position the infant was in when spell occurred
  • Color change?  Tone change?
  • Was the infant trying to breathe?
  • What was the infant's condition following the spell? If they were back to normal, less likely to be a metabolic disease, CNS infection, trauma, or seizure
  • Are there discrepancies in the story?
  • Who lives in the home?  Who normally cares for the child?  Sick contacts at home and immunization status of family members (DPT)?
  • From the primary care physician:  How is the child doing overall?  Growth curve?  Newborn screen results?  Any symptoms suggestive of the above mentioned etiologies?  Any red flags about the family socially?  Missed appointments?  Immunization delays?  Unexplained physical findings?
  1. Family History
  • Seizures                           
  • Unexplained deaths or drownings
  • Arrhythmias
  1. Medical/Birth History
  • Prematurity          
  • BPD
  • History of reflux and using medications
  • History of seizures
  • Results of newborn screen testing
  1. Physical examination
  • Thorough physical examination including fundoscopic exam, palpation of ribs & long bones for swelling or tenderness, abnormal reflexes for age, abnormal 
  1. Laboratory and other tests - only as indicated and dependent on history and findings
  • Should not obtain a WBC count, blood culture, or CSF analysis or cultures to detect an occult bacterial infection

Treatment

  1. Monitoring may be required (i.e., hospitalization) if the etiology appears to be life-threatening and/or if there are features that suggeset the etiology may be more high risk, such as:
  • Multiple BRUEs within 24 hours or up to 1 month of age
  • Serious central hypoventilation
  • Young age & history of significant symptomatic prematurity
  • Abnormal physical exam findings
  • 2 or more siblings who died of SIDS
  • One or more episodes requiring mouth-mouth resuscitation or vigorous stimulation
  1. Follow up
  • Good communication between the emergency department and ward teams with the primary care provider is essential to ensure properly folow up and monitoring.  
  • Some serious etiologies of BRUEs may not be apparent at first, thus follow up on behalf of the primary care provider is necessary to  enable a future diagnosis if there is one.
  1. Parental reassurance & education is key.
  • ​Advise on safe sleep practices and the dangers of tobacco smoke exposure
  • In some situations, caretakers should be taught basic life support
  • Parents should be reminded not to shake the infant

References

(2015). “Alphabet Soup: SIDS, ALTE, BRUE.” Department of Neonatology, Stanford University. Retrieved 15 May 2016 from  http://neonatology.stanford.edu/content/dam/sm/neonatology/documents/5minFriday_Alphabet%20Soup.pdf

Bakes, Katherine. (2016, April 25). “BRUE, the New ALTE.” NEJM Journal Watch. Retrieved 13 May 2016 from www.jwatch.org/na41150/2016/04/25/brue-new-alte

Brooks JG. (1992, December). Apparent life-threatening events and apnea of infancy. Clin Perinatology.

Claudius I, Mittal MK, Murray R, Condie T, Santillanes G. Should infants presenting with an apparent life- threatening event undergo evaluation for serious bacterial infections and respiratory pathogens? J Pediatr. 2014;164(5):1231–1233, e1

McGovern MC, Smith MB. (2004, November). Causes of apparent life threatening events in infants: a systematic review. Arch Dis Child.

Mittal MK, Shofer FS, Baren JM. Serious bacterial infections in infants who have experienced an apparent life-threatening event. Ann Emerg Med. 2009;54(4):523–527

Tieder, JS, Bonkowsky, JL, Etzel, RA, et al. (2016, May). “Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants.” Pediatrics. Retrieved 13 May 2016 from http://pediatrics.aappublications.org/content/pediatrics/early/2016/04/21/peds.2016-0590.full.pdf 

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