Continuing Education Activity

In 2016, the American Academy of Pediatrics recommended replacing the term apparent life-threatening event (ALTE) with brief resolved unexplained event (BRUE) to better reflect the non life-threatening, transient nature of these events. A BRUE is a transient event with no clear cause that is frightening to the observer and consists of a combination of apnea, color change, muscle tone change, and choking, or gagging in an infant. This activity describes the pathophysiology of the brief resolved event and highlights the role of the interprofessional team in the management and follow-up of these patients.

Objectives:

• Summarize a brief resolved unexplained event (BRUE).
• Identify the workup for an infant with a resolved unexplained event (BRUE).
• Identify keys to successful patient and caregiver management for infants that have undergone brief resolved unexplained events.
• Explain the importance of improving care coordination amongst interprofessional team members to improve outcomes for patients and families affected by brief resolved unexplained events.

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.

A 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
• The first brief resolved unexplained event (no previous brief resolved unexplained event ever and not occurring in clusters)
• The event lasts less than one minute
• No CPR is required by the trained medical provider
• No concerning historical features or physical examination findings.

Patients who do not meet the 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

The brief resolved unexplained event was 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 in the Lombardy region, Italy[6] had a cumulative incidence of 4.1 cases per 1000 live births. 

Pathophysiology

As brief resolved unexplained event is an unexplained event, the pathophysiology of these events is unknown. However, the possible role of abnormalities in the swallowing mechanisms, laryngospasm, gastroesophageal reflux, and 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 a 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 the event, abrupt or gradual termination, spontaneous termination, or any interventions used (picking up, rubbing, CPR), and behavior before returning 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 events are well and appear to have normal vital signs and physical exam findings. However, a thorough physical exam is required to identify those with a 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 events; 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 previously 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 the management of high-risk BRUE.

Differential Diagnosis

Several conditions can present with a brief apneic 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 events. Other conditions to consider include sepsis, meningitis, gastroesophageal reflux, seizures, infant botulism, prolonged QT syndrome, metabolic disorders, and child abuse.

Prognosis

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

Complications

There are 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 an interprofessional 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 (e.g., meningitis).