Brief Resolved Unexplained Event (BRUE)

Disclaimer These guidelines have been produced to guide clinical decision making for the medical, nursing and allied health staff of Perth Children’s Hospital. They are not strict protocols, and they do not replace the judgement of a senior clinician. Clinical common sense should be applied at all times. These clinical guidelines should never be relied on as a substitute for proper assessment with respect to the particular circumstances of each case and the needs of each patient. Clinicians should also consider the local skill level available and their local area policies before following any guideline.  Read the full PCH Emergency Department disclaimer.

Aim

This guideline provides an evidence based framework for the uniform and safe management of infants presenting at Perth Children’s Hospital with a Brief Resolved Unexplained Event (BRUE) – previously referred to as Apparent Life Threatening Event (ALTE).

Definitions

This guideline will refer to all events as BRUE noting that evidence from literature is based on previous ALTE definitions.¹

BRUE is described as an event observed in an infant (<1 year) which is:

• sudden
• brief (<1 minute)
• now resolved
• unexplained

BRUE involves at least one of ¹:

• Colour change - central cyanosis or pallor only
• Breathing change – absent, decreased or irregular
• Marked change in tone – hypertonia or hypotonia
• Altered level of responsiveness.

There are many medical causes of BRUE-like events. The term BRUE is applied only when a medical cause of the event is not established.

Key points

• The incidence previously described for ALTE was approximately 1 case per 1,000 live births.
• Recurrences generally occur within the first 24 hours of the first episode.
• In the majority of cases of BRUE, although the cause is not clearly established, it is thought that exaggerated physiological responses to feed/vomit or secretions may contribute.^1-4
• Episodes of redness are common among healthy infants and are not consistent with BRUE.
• BRUE can be classified into high risk and low risk with differing investigation and management approaches for the two groups. See BRUE Summary Flowchart below.
• Extensive investigation has a low identification yield and is generally unwarranted. Targeted testing is more appropriate and depends on a good clinical history.^1,2,6 
• The association between Sudden Infant Death Syndrome (SIDS) and BRUE remains to be clarified. Current evidence is that there is minimal risk of subsequent SIDS after a BRUE-like event.¹
• There is a higher risk of subsequent death after events in infants exposed to maternal smoking (e.g. SIDS) and with Non Accidental Injury (NAI) presenting as BRUE. 

History

Obtain a thorough history including:

• Description of the event:
  • what alerted caregiver to the problem
  • condition of child at time of event – colour, tone, respiratory effort (duration of apnoea or choking/gagging), responsiveness and any abnormal movements, eye deviation, vomiting
  • relationship to feed
  • where was the baby: sleep environment, position
  • awake/asleep
  • degree of intervention/resuscitation required and duration
• Relevant past medical history: prematurity, immunisation, recent illnesses
• Infective symptoms and contacts
• Feeding history: breast or bottle, vomiting or posseting, symptoms of Gastro-oesophageal Reflux Disease (GORD), 
• Drug exposure – including maternal medications if breastfeeding
• Developmental delay
• Previous episodes of BRUE
• Family history: SIDS/SUDI, epilepsy, metabolic disorder, cardiac
• Smoking 
• SIDS Risk Factors:
  • Prematurity and low birth weight
  • Modifiable risk factors including:
    • Unsafe sleep practices
    • See What are the risk factors - Red Nose
    • Exposure to smoking, before and after birth
    • Parental substance use

Examination

• Vital signs including pulse oximetry is essential
• Thorough multisystem examination bearing in mind possible causes
• Growth
• Dysmorphic features / craniofacial abnormalities.

Examination 

• Vital signs including pulse oximetry is essential
• Thorough multisystem examination bearing in mind possible causes 
• Basic assessment of all growth parameters, noting dysmorphic features.

Differential diagnoses ^1-5

The three most common differentials of BRUE include: 

• Gastro-oesophageal Reflux Disease (GORD)
• Lower Respiratory Tract Infection (LRTI)
• Seizures.

Cause	Incidence	Notes	Investigations
GORD	20-50%	Exaggerated physiological airway protection reflexes or ‘laryngospasm’  Choking and gagging common Do not routinely prescribe acid suppression therapy	Oesophageal Impedance and pH studies generally not helpful Consider upper GI and swallow contrast studies only for aspiration or anatomical abnormalities Consider Speech Therapy evaluation if feeding difficulties
LRTI Bronchiolitis Pneumonia	7-8%	Low incidence of apnoea with bronchiolitis: 1% term infants More likely if premature	Nasopharyngeal Aspirate (NPA) and CXR considered only if important to management
Neurological Seizures Infection Head injury Neuromuscular / hypotonia Cerebral malformation CNS Tumour	4-11% seizures	Consider inflicted injury	EEG may be indicated for recurrent episodes Cranial imaging - may be indicated for trauma or abnormal neurological examination
Serious bacterial infection UTI Bacteraemia Meningitis Sepsis Pertussis	<3%	BRUE is occasionally 1st presenting symptom Low rates (2.7% of all BRUE) of serious bacterial infection: more likely if premature or <60 days	NPA: viral, pertussis FBP +/- inflammatory markers Cultures: blood, urine, CSF Follow febrile infant guideline
Airway obstruction Foreign body Congenital anomaly -vascular ring, laryngeal, TOF Tonsils/adenoids Choanal atresia Hypotonia			Upper GI contrast for vascular ring/aberrant anatomy Consider ENT referral
Aponea: central or obstructive Apnoeas of prematurity Breath-holding Periodic breathing		Periodic breathing (brief pauses up to-10 sec without colour change) Short central apnoea <15 secs is normal in all age-groups Apnoea of prematurity may persist until 5 weeks of corrected age Rarely, breath holding spells- can occur <6months, emotional precipitant	Sleep study occasionally indicated following admission
Surgical abdomen Intussusception Volvulus Incarcerated hernia			Ultrasound Plain and erect Abdominal X-ray
Cardiac Arrhythmias/SVT/ long QT Congenital heart disease Cardiomyopathy Vascular ring	Uncommon in BRUE (<1%) and high false positive rate with cardiac investigations		ECG (sensitive but not specific) CXR Holter monitoring
Metabolic Inborn error of metabolism (IEM) Hypoglycaemia Hypocalcaemia Drug exposure	Rare	Significant unexplained metabolic acidosis – consult metabolic physician	BGL Blood gas Electrolytes (UEC) Urine metabolic screen Urine toxicology Lactate/pyruvate Ammonia, acyl-carnitine profile, plasma amino acids Consider coags, LFT’s
Inflicted injury Poisoning Smothering Abusive Head trauma (AHT)	Up to 2% Known risk factors: Delay in presentation SIDS in siblings Recurrent episodes	Subsequent mortality can be as high as 9%16 Note signs of AHT: vomiting, irritability, seizures, focal physical findings on exam (skin, mouth, extremities) Examine nose and mouth for blood Consider calls to emergency services	Urine toxicology CXR for rib fractures Cranial imaging Skeletal survey Fundoscopy FBP for anaemia Always involve CPU if ordering multiple investigations
Other Dehydration Severe anaemia Electrolyte disturbance Anaphylaxis

Investigations and management ^1-7

Immediate investigations to be considered in the Emergency Department:

• Blood gas and glucose
• Nasopharyngeal swab for pertussis
• ECG (QT interval)
• Septic workup where indicated.

Low risk BRUE ^1,2

Categorised low risk when there are no concerning features on history or examination AND all of the following:

• First and single event
• Duration < 1 minute
• Nil significant intervention (CPR) required
• Age >60 days
• Born ≥ 32weeks gestation and now >45 weeks corrected gestational age
• No cause for event identified
• Normal physical examination and vital signs.

Management of low risk BRUE

• Generally does not require admission and further investigation. 
• If significant caregiver anxiety is present, discussion with general paediatric team is suggested.
  • Brief (1-4 hours) continuous pulse oximetry may be considered. Refer to a general paediatric team.
  • NPA for pertussis and ECG may be performed in selected cases.
• Provide reassurance and written / verbal information and education to caregivers:
  • PCH infant resusitation pamphlet available from the Staff Development Nurse
  • Fact sheet: BRUE, Pediatric Patient Information
  • Information about safe infant sleep practices:
    • Brochures are available in ward areas or for download from Red Nose
    • Mobile Apps also available
    • Basic Life Support (BLS) training should be recommended to caregivers (PCH does not recommend specific providers) 
• Early follow up with Paediatrician or healthcare provider is recommended
• Always consider SIDS risk factors⁵ and inflicted injury prior to discharge ^9,10.

High risk BRUE 

• In cases that do not meet criteria for low risk, an underlying cause or serious medical problem may be possible. 
• Further investigation and admission under general paediatrics may be warranted.
  • Ward monitoring for up to 24 hours should include continuous pulse oximetry as a minimum ^1,4,8
  • Respiratory monitoring (inductance plethysmography) for apnoea and cardiac monitoring may also be considered.

Monitoring ^8,11

• Referral to infant monitoring clinic is generally not indicated for low risk BRUE. 
• Referral process to the Infant Monitoring Service is outlined on the PCH Department of General Paediatrics information page (internal HealthPoint link)
• Commercially available home monitors are not recommended but may provide reassurance. Note that apnoea has not been established as the primary event leading to SIDS and that there is no evidence that home monitoring of healthy infants saves lives
• Refer to Red Nose Information Statement: home monitoring 

References

1. Ramgopal S, Noorbakhsh KA, Callaway CW, Wilson PM, Pitetti RD. Changes in the Management of Children With Brief Resolved Unexplained Events (BRUEs). Pediatrics. 2019;144(4):e20190375.
2. Tieder JS, Bonkowsky JL, Etzel RA et al. Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower Risk Infants. Pediatrics. 2016;137(5):e20160590
3. Kiechl-Kohlendorfer U, Hof D, Pupp Peglow U, Traweger-Ravanelli B, Kiechl S. Epidemiology of apparent life threatening events. Arch Dis Child. 2004;90:297-300.
4. McGovern MC, Smith MBH. Causes of apparent life threatening events in infants: a systematic review. Arch Dis Child 2004;89:1043-8.
5. Esani N, Hodgman J, Eshani N, Hoppenbrousers T. Apparent Life-Threatening Events and Sudden Infant Death Syndrome: A Comparison of Risk Factors. Journal of Pediatrics. March 2008;152:365-70.
6. Brand DA, Altman RL, Purtill K, Edwards KS. Yield of diagnostic testing in infants who have had an apparent life-threatening event. Pediatrics. 2005;115:885-93.
7. Royal Children’s Hospital, Melbourne, Australia. Clinical Practice Guideline: Brief Resolved Unexplained Event. Clinical Guideline 2020. Available from: https://www.rch.org.au/clinicalguide/guideline_index/Brief_Resolved_Unexplained_Event_BRUE/ (Accessed 3 March 2021)
8. Bonkowsky J L, Guenther E, Filoux F M, R S. Death, child abuse, and adverse neurological outcome of infants after an apparent life-threatening event. Pediatrics. 2008;122:125-31.
9. Parker K, Pitetti R. Mortality and Child Abuse in Children Presenting with Apparent Life-Threatening Events. Pediatr Emerg Care. July 2011;27(7):591-5
10. Fu LY, Moon RY. Apparent Life-threatening Events (ALTEs) and the role of home monitors. Pediatrics in Review. 2007 ;28:203-8.

Approved by:	PCH Clinical Practice Advisory Committee	Date:	Mar 2021
Endorsed by:	Director, Clinical Services	Date:	26 Mar 2021
		Review date:	Mar 2024

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