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    Patent Pending

    Brief Resolved Unexplained Events (BRUE) Criteria for Infants

    Classifies unexplained events and replaces the Apparent Life Threatening Events (ALTE) classification.
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    INSTRUCTIONS

    Use in infants <1 year old who are asymptomatic and in their normal state of health at the time of evaluation. Do not use in symptomatic patients (e.g. fever, respiratory distress) or those with obvious cause for prior symptoms.

    When to Use
    Pearls/Pitfalls
    Why Use

    Infants <1 year old presenting for evaluation after a brief, unexplained, and now resolved event consisting of ≥1 of the following:

    • Cyanosis or pallor.
    • Absent, decreased, or irregular breathing.
    • Marked change in tone.
    • Altered level of responsiveness.
    • Developed via expert consensus by the American Academy of Pediatrics (AAP).
    • The criteria require that an extensive history and physical examination have failed to reveal a cause of the episode.
    • Can be used in inpatient, outpatient, and emergency department settings.
    • Note that choking, gagging, and red color change, which were part of the ALTE definition, are not part of the BRUE Criteria.
    • Risk is defined by the likelihood of adverse recurrent events or eventual diagnosis of a serious underlying disorder.
    • BRUEs represent a separate entity from sudden infant death syndrome (SIDS).
    • Replaces the term ALTE, which is broader and does not identify patients who are lower risk.
    • May give providers comfort in discharging lower risk BRUE patients home.
    • May reduce the need for unnecessary diagnostic testing which may be invasive and expensive.
    Entry criteria

    Must fulfill all 4 to evaluate for BRUE

    Diagnostic Result:

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    Next Steps
    Evidence
    Creator Insights

    Advice

    Key action statements from AAP for lower risk infants (adapted from Tieder 2016):

    Recommendation

    Level of Evidence

    Strength of Recommendation

    Should do

    Assess social risk factors to detect child abuse

    C

    Moderate

    Offer CPR training resources

    C

    Moderate

    Educate about BRUEs

    C

    Moderate

    Use shared decision-making

    C

    Moderate

    Should NOT do

    Chest x-ray

    B

    Moderate

    VBG or ABG

    B

    Moderate

    Overnight sleep study

    B

    Moderate

    Echo

    C

    Moderate

    Home cardiorespiratory monitoring

    B

    Moderate

    Neuroimaging (CT, MRI, or ultrasonography) to detect neurologic disorders

    C

    Moderate

    EEG to detect neurologic disorders

    C

    Moderate

    Antiepileptic medication

    C

    Moderate

    WBC count, blood culture, or CSF analysis or culture to detect occult bacterial infection

    B

    Strong

    Chest x-ray to assess for pulmonary infection

    B

    Moderate

    Investigations for GER (e.g. upper GI series, pH probe, endoscopy, barium contrast study, nuclear scintigraphy, ultrasound)

    C

    Moderate

    Prescribe acid suppression therapy

    C

    Moderate

    Serum Na, K, Cl, BUN, Cr, calcium, or ammonia

    C

    Weak

    VBG or ABG

    C

    Moderate

    Urine organic acids, plasma amino acids, or plasma acylcarnitines

    C

    Moderate

    Laboratory evaluation for anemia

    C

    Moderate

    May do

    Briefly monitor with pulse oximetry and serial observation

    D

    Weak

    12-lead EKG

    C

    Weak

    Pertussis testing

    B

    Weak

    Not needed

    Admission solely for cardiorespiratory monitoring

    B

    Weak

    Neuroimaging (CT, MRI, or ultrasonography) to detect child abuse

    C

    Weak

    Urinalysis (bag or catheter)

    C

    Weak

    Respiratory viral testing

    C

    Weak

    Serum lactic acid or bicarbonate

    C

    Weak

    Blood glucose

    C

    Moderate

    Level A

    • Intervention: well-designed and well-conducted trials, meta-analyses.
    • Diagnosis: Independent gold standard studies.

    Level B

    • Trials or diagnostic studies with minor limitations.
    • Consistent findings from multiple observational studies.

    Level C

    • Single or few observational studies, or
    • Multiple studies with inconsistent findings or major limitations.

    Level D

    • Expert opinion.
    • Case reports.
    • Reasoning from first principles.

    Level X

    • Exceptional situations where validating studies cannot be performed and there is a clear preponderance of benefit/harm.

    Levels of evidence, from Tieder 2016:

    Critical Actions

    • Evidence-based guidelines for evaluation and management should only be applied to patients categorized as having had a lower risk BRUE.
    • An appropriate social history and examination is critical to screen for potential child abuse and neglect.
    • BRUE Criteria and evidence-based recommendations are not a substitute for individual physician judgment.

    Formula

    To be classified as a BRUE, all of the following must be true:

    • Infant <1 year old.
    • Asymptomatic on presentation (no URI symptoms, no fever).
    • No explanation for the event after conducting history and physical (e.g. GER, feeding difficulties).
    • History of sudden, brief, and now resolved episode consisting of ≥1 of the following:
      • Cyanosis or pallor.
      • Absent, decreased, or irregular breathing.
      • Marked change in tone (hyper or hypotonia).
      • Altered level of responsiveness.

    Then, for a BRUE to be classified as low risk, all of the following must also be true:

    • Episode duration <1 minute.
    • >2 months of age.
    • No history of prematurity.*
    • No prior BRUE.
    • No need for CPR by medical provider.

    *≥32 weeks gestational age or ≥45 weeks postconceptional age for infants born at <32 weeks.

    Evidence Appraisal

    The BRUE Criteria and risk stratification algorithm were created in 2016 as a clinical practice guideline published by the American Academy of Pediatrics. A comprehensive review of the available ALTE literature was performed and used to inform key action statements. When definitive data was not available, expert consensus of a multidisciplinary committee was used.

    The guidelines were created with the following goals:

    • Replace the term apparent life-threatening event (ALTE) with brief resolved unexplained event (BRUE).
    • Allow stratification of patients who present with a BRUE into low and higher-risk categories.
    • Provide evidence-based guidelines for the evaluation and management of patient categorized as lower risk.

    Risk in patients presenting with a BRUE was defined by risk of either adverse recurrent events or eventual diagnosis with a serious underlying disorder. Several studies in the ALTE literature have attempted to identify predictive variables of this risk.

    Claudius and Keens performed a prospective observational analysis of all children presenting with ALTE (Claudius and Keens, 2007). Of the 59 infants included, 8 were deemed to necessitate admission, with age <30 days and the presence of multiple reported events identifying all patients. Prematurity was also noted to be a significant risk factor, though inclusion did not identify any additional patients.

    In a retrospective cohort study of 625 patients admitted for ALTE, Al-Kindy et al identified risk factors for “extreme” vital sign changes (e.g. sustained bradycardia, apnea, or desaturation), including post-conceptional age <43 weeks, premature birth, and URI symptoms.

    Mittal et al performed a prospective cohort study of 300 infants evaluated in the ER for ALTE. Logistic regression identified prematurity, abnormal physical examination, cyanotic color change, and the absence of URI symptoms and choking as significant predictors of need for admission.

    Kaji et al reported on factors predictive of need for admission in a multi-institution, observational cohort study of 832 patients presenting with ALTE. Aside from obvious need for admission at the time of initial evaluation (e.g. oxygen requirement), a significant medical history (e.g. cardiopulmonary or neuromuscular disease) and the presence of >1 event in the preceding 24 hours identified the majority of patients requiring admission.

    Lastly, a systematic review of 37 studies by Tieder et al sought to determine risk factors for future adverse events and/or serious underlying diagnosis. Risk factors included history of prematurity, multiple ALTEs, and suspected child maltreatment.

    Notably, the BRUE Criteria were created based on systematic review of the ALTE literature. As such, prospective studies are needed to define the true incidence of BRUE, determine final diagnoses and outcomes of both low and higher-risk infants, and elucidate the role and utility of diagnostic testing in higher-risk infants.

    Literature

    Other References

    Research PaperZwemer E, Claudius I, Tieder J. Update on the Evaluation and Management of Brief Resolved Unexplained Events (Previously Apparent Life-Threatening Events). Rev Recent Clin Trials. 2017;12. doi:10.2174/1574887112666170816150104.Research PaperClaudius I, Keens T. Do all infants with apparent life-threatening events need to be admitted?. Pediatrics. 2007;119(4):679-83.Research PaperAl-kindy HA, Gélinas JF, Hatzakis G, Côté A. Risk factors for extreme events in infants hospitalized for apparent life-threatening events. J Pediatr. 2009;154(3):332-7, 337.e1-2.Research PaperMittal 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. Pediatr Emerg Care. 2012;28(7):599-605.Research PaperKaji AH, Santillanes G, Claudius I, et al. Do infants less than 12 months of age with an apparent life-threatening event need transport to a pediatric critical care center?. Prehosp Emerg Care. 2013;17(3):304-11.Research PaperTieder JS, Altman RL, Bonkowsky JL, et al. Management of apparent life-threatening events in infants: a systematic review. J Pediatr. 2013;163(1):94-9.e1-6.
    Dr. Joel S. Tieder

    About the Creator

    Joel S. Tieder, MD, MPH, is a pediatric hospitalist and associate professor of pediatrics at Seattle Children's Hospital and the University of Washington School of Medicine. Dr. Tieder's research interests include quality of care for hospitalized pediatric patients, more specifically in urinary tract infection, community acquired pneumonia, and diabetic ketoacidosis.

    To view Dr. Joel S. Tieder's publications, visit PubMed

    Content Contributors
    • Eric Zwemer, MD
    About the Creator
    Dr. Joel S. Tieder
    Content Contributors
    • Eric Zwemer, MD