Which Is BRUE

According to the American Academy of Pediatrics, ALTE is out, and BRUE is in. Here’s what you need to know about Brief Resolved Unexplained Events.

It’s been a steady night. A nurse hands you the chart for the baby in room 5, saying “that baby looks fine, there’s not a thing wrong with her”. You walk in with a 4th year medical student and can’t help smiling at the cute little 4 month-old with her toothless smile, all four extremities moving at once to show how happy she is to get your attention. She gurgles. You’re hooked. Glancing at her vitals gives nothing away. This child is the picture of health. Her worried parents share the following story:

About an hour prior to arrival, this little buttercup had finished her bottle and the mother was carrying her in her arms while she was on the phone. She looked down and the child seemed limp and the mother could not discern if she was breathing. The mother dropped the phone and lay the baby down and after 10-20 seconds the baby began to cry. By the time EMS arrived she was back to her baseline. The mother reports the whole episode lasted less than a minute but really scared her.

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On further history you learn that the baby was the full term product of an uneventful labor and delivery, without major medical problems up to this point. She was in her usual state of heath today leading up to tonight’s episode. The parents seem reasonable and attentive, and report that the patient has been growing well, has met all her milestones, and has never missed a scheduled well-child check. The family history is negative for sudden cardiac death, SIDS, seizures or major medical problems in children. Your physical exam is positive for a happy, drooling baby with no concerning findings. The medical student asks what you are going to do?

The student has been doing some reading. “This is an ALTE, right?” he asks.

“No, you say, this is a BRUE.”

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“What’s BRUE?”

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An ALTE is an older term meaning Apparent Life Threatening Event. It implied that something potentially serious had happened to the infant and required various versions of a work-up and/or admission. A recently published American Academy of Pediatrics (AAP) clinical practice guideline replaces the term ALTE with the term BRUE, which stands for Brief Resolved Unexplained Event. The guideline also provides a strategy to assess the risk for a serious underlying problem and/or a repeat event. Patients are assigned to lower or higher risk based on this assessment. Finally, the guideline suggests management of the lower-risk group. The guideline does not apply to infants deemed higher risk.

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Per the AAP guideline a BRUE is an event that:

• Occurs in an infant < 1 year of age
• Includes > 1 of the following:
  • Cyanosis or pallor
  • Absent, decreased, or irregular breathing
  • Marked change in tone, either hypertonia or hypotonia
  • Changed level of responsiveness
• No explanation after a thorough, appropriate history and physical exam

Who is a lower risk infant?

• Age > 60 days
• Gestational age > 32 weeks and post-conceptual age > 45 weeks
• One event only; no prior BRUE, no cluster of BRUEs
• The BRUE itself should last less than one minute
• The event should not have required CPR by trained medical personnel
• There should be no concerning history or physical examination elements

Who is a high-risk infant?

• Those not meeting age or timing criteria
• Concerns identified from history or examination
• Family history of sudden cardiac death, or subtle, non-diagnostic social, feeding or respiratory problems

For low-risk infants, ED interventions should be minimal. The main intervention is to educate the parents about BRUE. Assure parents that this is a low-risk situation and the infant is unlikely to have any adverse outcome. It is wise to obtain an ECG and institute a brief period of cardiac monitoring with continuous pulse oximetry and repeat examination while in the ED. Consider pertussis testing, taking into account vaccination history and the potential for exposure. There are no recommendations about the duration of ED monitoring. We might also use this visit as a chance to refer parents to an infant CPR class, but only because this is a reasonable general practice, not to imply that this child is at any increased risk of requiring resuscitation. Share decision-making with the parents.

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For a low-risk BRUE, the guideline advises against blood work, sepsis evaluation, lumbar puncture, chest films, echo, reflux or seizure medication or sending families home with a monitor. You do not need to send respiratory viral studies, check blood sugar, lactate, bicarbonate or do any neuroimaging. Admission for observation and monitoring is not necessary either.

For a high-risk BRUE, admit the patient for cardiorespiratory monitoring and further assessment for underlying cause of the event.

Understanding the New Guidelines
ALTE was meant to replace “near-miss sudden infant death syndrome (SIDS)” and is defined as “an episode that is frightening to the observer and that is characterized by some combination of apnea (central or occasionally obstructive), color change (usually cyanotic or pallid but occasionally erythematous or plethoric), marked change in muscle tone (usually marked limpness), choking, or gagging. In some cases, the observer fears that the infant has died.” (McGovern et. al). Patients who present with an ALTE often undergo a battery of tests in the emergency department and are admitted for serial exams and further workup. However, the reality is that ALTEs are rarely the initial presentation of significant illness or disease. A systematic review of ALTE publications by Joel Tieder et al. identified certain patients at lower risk for a recurrent event or an undiagnosed serious condition, but was unable to definitively quantify risk for subsequent or underlying serious condition due to the vague characterization of ALTE. Indeed, the imprecision of the initial ALTE definition is the motivation behind the new BRUE clinical practice guideline. The term BRUE, as described in the guideline, “is intended to better reflect the transient nature and lack of clear cause and removes the ‘life-threatening’ label.”

Application of a strict BRUE definition to a discrete lower risk population allows for judicious use of medical resources. Infants without identifiable risk factors are unlikely to benefit from admission or diagnostic procedures including laboratory and imaging studies. Key action statements in the new guideline are intended to a create clear, transparent, and actionable management plan for high-risk BRUE infants. These key action statements encompass eight topics: 1) cardiopulmonary evaluation, 2) child abuse evaluation, 3) neurologic evaluation, 4) infectious disease evaluation, 5) gastrointestinal evaluation, 6) inborn error of metabolism (IEM) evaluation, 7) anemia evaluation, and 8) patient and family-centered care. As per the guideline, “strong and moderate recommendations are associated with ‘should’ and ‘should not’ recommendation statements, whereas weak recommendations may be recognized by use of ‘may’ or ‘need not’”. Weak recommendations, in particular, are an excellent opportunity to include the family in clinical decision-making.

The definition of a lower-risk BRUE requires a normal physical exam; evaluation in a single spot in time may not be as accurate as a longer period of observation. From a cardiovascular standpoint, clinicians may consider briefly monitoring patients with continuous pulse oximetry and serial observations. Length of observation should be a shared decision between family and physician. Clinicians also may consider obtaining a 12-lead EKG to identify patients with channelopathies (long QT syndrome, short QT syndrome, and Brugada syndrome), ventricular preexcitation (Wolff-Parkinson-White syndrome), cardiomyopathy, or other heart disease.

Child abuse, in particular abusive head trauma, is a known cause of ALTE, but the presentation is often subtle. Consequently, the guideline recommends physicians obtain an assessment of social risk factors for child abuse. This evaluation includes a thorough history and physical examination; especially concerning findings include a developmentally inconsistent or discrepant history, a previous ALTE, a recent emergency services call, vomiting, irritability, or bleeding from the nose or mouth. Based on the ALTE systemic review, the incidence of abusive head trauma was < 0.3% for patients meeting lower-risk BRUE criteria. Given the risk of radiation exposure, risk of sedation, and potential for false-positive results the guideline does not recommend routine neuroimaging.

Seizures or abnormal brain architecture can present as a BRUE. Despite this, available evidence suggests minimal benefit of CNS imaging and EEG in patients deemed as lower risk. Both recommendations are “moderate” in part due to the lack of benefit and potential harm of the studies, but also due to lack of evidence that initiation of therapy after a first-time seizure is beneficial. For similar reasons, clinicians should not prescribe antiepileptic medications for potential neurologic disorders in infants presenting with a low risk BRUE.

Infectious disease should always be considered. Interestingly, the only “strong” recommendation in this guideline is clinicians “should not obtain a WBC count, blood culture, or cerebrospinal fluid analysis or culture to detect an occult bacterial infection.” Review of ALTE literature reveals that patients found to have serious bacterial infections, such as bacteremia and meningitis, would not qualify as lower-risk BRUE. In addition to cost, unnecessary exposure to antibiotics, and the possibility of false-positive results, work-up is invasive and painful and should be avoided. UTI, pneumonia, and respiratory viral infections have been reported as causes of ALTE, but again, the evidence is not compelling and patients with these disease processes are unlikely to be asymptomatic or to meet the definition of lower-risk BRUE. Urinalysis, chest radiography, and rapid viral testing are not recommended. If the decision is made to collect a urinalysis, a urine culture should also be obtained. Pertussis infection in infants can cause coughing, gagging, and apnea. Due to indolent disease progression, a patient with pertussis may present with an apparent lower-risk BRUE, only later to develop respiratory symptoms. For these reasons the guideline recommends that clinicians may obtain testing for pertussis in infants with a lower-risk BRUE. The decision to test should include consideration of potential exposures, maternal and infant vaccine history, pertussis prevalence in the community, and turnaround time for results.

Gastroesophageal reflux (GER) is common in infancy and historically many ALTEs have been attributed to GER. Laryngospasm secondary to GER has been proposed as an etiology of ALTEs. BRUEs caused by reflux-related laryngospasm may not be clinically evident at the time of presentation, on the other hand laryngospasm during feeding may occur without GER. Despite the prevalence of GER, available evidence supports neither the routine use of diagnostic investigations (such as pH probe, endoscopy, barium contrast study, nuclear scintigraphy, and ultrasound) nor treatment with acid suppression therapy for infants presenting with lower-risk BRUE. Although newer tests such as combined pH and multiple intraluminal impedance may be considered in patients with recurrent BRUE or GER symptoms, lack of standardized technique and inability of testing to determine pathologic reflux precludes the utility of common investigative modalities in low risk patients. Patients with GERD (that is, disease implying complications from GER) should be considered for acid suppression therapy; however, research has not documented proven efficacy of such treatment for physiologic esophageal reflux. If GER is suspected the event, by definition, is not a BRUE. Instead of studies and medication, EPs should use the opportunity to stress symptomatic care. Initial management of GER includes the following “reflux precautions”: keep the infant upright during and after feeds (on the caregiver’s shoulder, not a car seat or infant carrier), frequent burps, and avoidance of secondhand smoke. Avoidance of overfeeding should also be stressed. Breastfed infants are reported to have a decreased frequency of GER; therefore, exclusive breastfeeding should be encouraged.

Based on numerous studies, IEMs are reported to cause ALTE in 0% to 5% of cases, but it is doubtful these events would even meet criteria for lower-risk BRUE. The history is critical in this scenario as symptoms of IEMs are unlikely to be brief or resolve without intervention (including feeding). Based on either lack of compelling evidence or poor quality of the evidence, the benefits of reducing unnecessary testing, cost, and false positive results outweigh the rare missed diagnostic opportunity for IEM. Consequently, the guideline does not recommend routine measurement of: serum lactic acid, bicarbonate, sodium, potassium, chloride, blood urea nitrogen, creatinine, calcium, ammonia, venous or arterial blood gas, blood glucose, urine organic acids, plasma amino acids, and plasma acylcaritines.

Even though multiple studies demonstrate an association between anemia and ALTEs in infants, normal hemoglobin concentration has been reported in many other ALTE populations. Thus, the clinical significance and causal association between anemia and the event are unclear. For this reason the guideline states clinicians should not obtain laboratory evaluation for anemia in infants presenting with a lower-risk BRUE.

This guideline frees EPs from pursuing unnecessary evaluation and admission for patients who present with what is deemed, after thorough history and physical examination, to be a low-risk BRUE. It also empowers them to be a strong patient and family advocate. For example, physicians may choose to follow AAP recommendations and encourage caregivers and the general public to receive life-support training as this can improve overall community health. Furthermore, EPs should educate caregivers about BRUEs and utilize shared decision-making to develop a management plan for infants presenting with a lower-risk BRUE. This give-and-take between informed caregivers and providers should “empower families and foster a stronger clinician-patient/family alliance as they make decisions together in the face of a seemingly uncertain situation.”

Getting back to our adorable little patient, let’s apply the new guideline. Here’s how it works:

• The infant is less than a year old.
• Her breathing was described as absent
• She became limp.

We perform an appropriate H & P. There is no explanation and there are no concerns from individual, family, or social history. Applying our risk stratification, she is lower-risk. What next?

After talking things over with the parents, we elect to place her on a cardiac monitor with continuous pulse oximetry in the ED and watch her for two hours. She feeds, sleeps and behaves like a normal infant and is discharged with appropriate return precautions and follow-up.