Brief Resolved Unexplained Event

Aka: Brief Resolved Unexplained Event, BRUE, Apparent Life-Threatening Events In Children, Apparent Life Threatening Event In Infant, ALTE

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II. Definitions

  1. Brief Resolved Unexplained Event (BRUE)
    1. Replaces Apparent Life-Threatening Event (ALTE)
    2. One of the following event types
      1. Altered Level of Consciousness
      2. Change in color (pallor, Cyanosis)
      3. Marked change in Tone (hyper- or hypotonia)
        1. Not the tone changes seen in Infantile Spasms or Seizures
      4. Respirations (apnea, irregular)
        1. Not the normal periodic breathing seen in newborns or breath holding seen in infants
        2. Not the Choking or gagging episodes associated with spitting-up
    3. Episode occurs in infant <1 year old
    4. Resolves within 1 minute, returning to baseline
    5. Event unexplained by findings
      1. No feeding difficulties or Pediatric Reflux
      2. No airway abnormalities
    6. Reassuring history, Vital Signs and exam
      1. Abnormal Vital Signs at time of evaluation (e.g. fever, Tachycardia, Tachypnea) excludes BRUE
      2. Abnormal exam (persistent mental status change, tone changes, Vomiting, Noisy Breathing) excludes BRUE
  2. Apparent Life-Threatening Event (ALTE)
    1. Original diagnostic criteria from 1986 and replaced by the BRUE Definition
    2. Sudden, brief episode with serious findings in an infant under age 1 year
    3. Presents with apnea, Cyanosis or pallor, limp, Choking or gagging

III. Epidemiology

  1. Incidence: Up to 1 in 400 infants
  2. Accounts for 0.6 to 0.8% of pediatric emergency department visits for infants under age 1 year old
  3. Occurs in infants under age 1 year (usually <10 weeks old)

IV. Risk Factors

  1. Male gender
  2. Feeding symptoms (rapid feeders, or feeding with cough)
  3. Age under 2 months
    1. More likely to have serious underlying condition (e.g. infection, metabolic disorder, congenital cardiac defect)
  4. Premature Infants, especially if accompanied by:
    1. Respiratory Syncytial Virus (RSV)
    2. General Anesthesia history

V. Causes

  1. General
    1. Idiopathic in 50% of cases
    2. No longer thought to be near-miss SIDS (older hypothesis)
  2. Gastrointestinal (50% of diagnosed cases)
    1. Pediatric Gastroesophageal Reflux
    2. Bowel disorder (Gastric Volvulus, Intussusception)
    3. Infantile Botulism
  3. Neurologic (30% of diagnosed causes)
    1. Seizure Disorder (e.g. Febrile Seizures)
    2. Vasovagal reflex
    3. Structural Disease (Budd-Chiari Syndrome)
    4. Brain Mass
    5. Meningitis (or other CNS Infection)
    6. Increased Intracranial Pressure (e.g. Hydrocephalus)
    7. Intracranial Hemorrhage or Trauma (e.g. Shaken Baby Syndrome)
  4. Respiratory (20% of diagnosed causes)
    1. Infection (RSV, Pertussis, Croup)
    2. Breath-Holding Spell
    3. Apnea of Prematurity
    4. Obstruction (Sleep Apnea, vocal cord, foreign body)
    5. Laryngotracheomalacia
    6. Facial anomaly
  5. Cardiac (5% of diagnosed causes)
    1. Arrhythmia
    2. Congenital Heart Disease
    3. Cardiomyopathy
  6. Metabolic (<5% of diagnosed causes)
    1. Inborn Errors of Metabolism
    2. Endocrine disorder
    3. Toxic ingestion
    4. Hypoglycemia
    5. Hypocalcemia
  7. Infection
    1. Urinary Tract Infection
    2. Sepsis
  8. Child Abuse (<5% of diagnosed causes)
    1. Smothering
    2. Non-accidental Trauma
    3. Munchausen by proxy
      1. Consider in repeat episodes seen by only 1 person

VI. Symptoms

  1. Apnea
  2. Change in color (e.g. blue or cyanotic)
  3. Altered Muscle tone (floppy or stiff)
  4. Coughing, Choking or gagging

VII. History

  1. Event history
    1. Awake or asleep, prone or supine, and location?
    2. Occur with feeding, coughing, Choking, Vomiting?
    3. Respiratory effort? Skin Color? Muscle tone?
    4. Event duration?
    5. Interventions required (stimulation, CPR)?
  2. Recent illness
    1. Fever or rash
    2. Recent poor feeding or weight loss
    3. Irritable or Decreased Level of Consciousness
    4. Contagious contacts
  3. Medical history
    1. Prenatal and birth history
    2. Developmental Milestones met?
    3. Possible Trauma
    4. Prior similar episodes
    5. Family History (SIDS, neurologic or cardiac disorder)

VIII. Exam

  1. Comprehensive examination is critical
  2. Evaluate for underlying condition (see causes above)
  3. Pulse Oximetry

IX. Diagnostics

  1. Individualize testing by history and exam
    1. No routine test is absolutely indicated in BRUE (or ALTEs)
    2. Low-Risk BRUE requires no significant testing unless otherwise indicated by history or exam
  2. High yield testing to consider in low risk BRUE events
    1. Electrocardiogram (high Negative Predictive Value)
    2. Pertussis nasal swab (significantly higher risk of apnea)
    3. Blood Glucose
  3. Other testing in higher risk events
    1. Complete Blood Count (CBC)
      1. However, leads to diagnosis in <5% of cases
    2. Chemistry panel (Chem8)
      1. Serum Electrolytes including Calcium, Magnesium
      2. Serum Glucose (consider bedside Glucose)
      3. Serum bicarbonate
        1. Low level associated with more serious causes
        2. Consider checking serum lactate
    3. Urinalysis
    4. Chest XRay
    5. Pertussis nasal swab
    6. Respiratory Syncytial Virus (RSV) nasal swab
    7. Electrocardiogram (EKG)
  4. Additional evaluation to consider
    1. Blood Culture
    2. MRI Brain
    3. Lumbar Puncture
    4. Liver Function Tests

X. Evaluation: Brief Resolved Unexplained Event (BRUE)

  1. Low risk criteria (all must be met)
    1. Age >60 days
    2. Not premature (Gestational age >32 weeks and post-conceptual age >45 weeks)
    3. First and isolated event, with no prior history of BRUE
    4. Duration <1 minute
    5. CPR not required by trained medical provider
    6. No concerning history, Vital Signs or exam abnormalities
      1. Includes no concerns for Nonaccidental Trauma or serious Family History (e.g. unexplained young child death)
  2. Approach
    1. BRUE episode is high risk if not all low risk criteria are met
    2. Low risk events do not require hospitalization (but may still admit as indicated)
      1. However, if discharged, re-evaluate in 24 hours
    3. Home cardiorespiratory monitoring is NOT recommended

XI. Management: Low-Risk BRUE

  1. Observe in Emergency Department for 1 to 4 hours
    1. Negotiate length of observation period with parents
    2. May offer Pertussis testing, EKG
    3. May offer brief Pulse Oximetry monitoring
      1. Risk of over-diagnosis with the brief oxygen desaturations seen in normal infants
    4. Avoid reflex testing or empiric medications
      1. Avoid starting Pediatric Reflux medications or ordering reflux evaluation studies
      2. Avoid Seizure Prophylaxis
  2. Home precautions
    1. Recheck in 24 hours with repeat history and physical exam
    2. Return immediately for recurrent BRUE, difficult breathing, lethargy, poor feeding
    3. Discuss CPR training with parents
    4. Avoid home cardiac or respiratory monitoring

XII. Management: High Risk BRUE

  1. Perform testing as above (including RSV, Pertussis, EKG)
  2. Monitor with prolonged oximetry on the hospital ward
    1. Do not discharge with oximetry (very high False Positive Rate and not protective)
  3. Hospital observation and monitoring in most cases
    1. See high-risk criteria as above
    2. Other indications
      1. Age under 2 months and history of prematurity
      2. Child Abuse risk factors (ALTE was associated with abuse in up to 3% of cases)
  4. Evaluation to consider
    1. Pediatric GERD is among the most common causes
      1. However, avoid empirically starting in BRUE (or ALTE) alone
      2. Consider thickening feeds and other non-medication management for Pediatric GERD
      3. In general, avoid Antacid therapy overall (does not alter course)
    2. Silent aspiration (feeding problem related) suspected
      1. Consider Videofluoroscopic Swallow Study (VFSS)
    3. Obstructive Apnea suspected
      1. Consult otolaryngology and pulmonology Consultation
      2. Consider Sleep Study
    4. Central apnea suspected
      1. Consider head imaging (e.g. MRI Brain)
      2. Consult pulmonology
    5. Seizures suspected
      1. Consult neurology
      2. Consider prolonged EEG (12 hours)
    6. Congenital Heart Disease or Arrhythmia suspected
      1. Consult cardiology
    7. Episodic Hypoglycemia or acidosis
      1. Consult biochemical Genetics
      2. Obtain serum chemistries (basic chemistry panel and ammonia level)
    8. References
      1. Merritt (2019) Pediatrics 144(2): e20184101 [PubMed]

XIII. Prognosis: Mortality risk

  1. Unclear how prior ALTE statistics apply to Low Risk BRUE
  2. ALTE was thought to be associated with increased SIDS risk
    1. However, BRUE events are not thought to be averted SIDS event
    2. ALTE after age 2 months predicted serious cause (but unclear if this applies to low risk BRUE)
      1. Davies (2002) Emerg Med J 19:11-16 [PubMed]
  3. Risk significantly increases with serious cause identified
    1. Central hypoventilation
    2. Seizure Disorders
    3. Cardiac Arrhythmia
    4. Shannon (1992) Clin Perinatol 19:861-9 [PubMed]

XIV. References

  1. Bellis (2020) Crit Dec Emerg Med 34(9): 21-5
  2. Claudius and Tieder in Herbert (2012) EM: Rap 12(9):2
  3. Claudius and Orman in Herbert (2016) EM:Rap 16(10): 4-5
  4. Loomis and Ponce (2019) Crit Dec Emerg Med 33(7): 25
  5. Davies (2002) Emerg Med J 19:11-6 [PubMed]
  6. Hall (2005) Am Fam Physician 71:2301-8 [PubMed]
  7. Tieder (2016) Pediatrics 137(5): e20160590 +PMID: 27244835 [PubMed]

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