Pediatric Apnea 

Updated: Sep 28, 2018
Author: Joshua A Rocker, MD; Chief Editor: Kirsten A Bechtel, MD 

Overview

Background

Apnea is defined by the cessation of respiratory airflow. The length of time necessary to be qualified as a true apneic event has changed dramatically over the last several decades: 2 minutes in 1956,[1]  1 minute in 1959,[2]  30 seconds in 1970,[3]  and then 20 seconds or shorter if associated with bradycardia or cyanosis in 1978.[4]  The reduction of the duration in the definition of apnea reveals doctors’ desire to intervene early enough to avoid systemic consequences.

The 3 main categories of apnea are central, obstructive, and mixed. Central apnea is a result of inadequate medullary responsiveness and thus results in no or poor muscle coordination for breathing. Obstructive apnea is when there is an obstruction of the airway passages and therefore poor to no air exchange. Often times with obstructive apnea, there is a vigorous inspiratory effort but it is ineffective against the obstruction. Mixed apnea refers to an episode where combinations of both central and obstructive forces are involved.

Infant apnea is defined by the American Academy of Pediatrics as "an unexplained episode of cessation of breathing for 20 seconds or longer, or a shorter respiratory pause associated with bradycardia, cyanosis, pallor, and/or marked hypotonia."[5]  Apnea is more common in preterm infants. Apnea of prematurity requires a specific assessment and treatment and is not discussed in full in this article. True apnea is rare among full-term healthy infants and, if present, may indicate an underlying pathology.

The ED physician may not experience many patients with pure apneic events but more likely will have an infant's caregiver come in and report that his or her child appeared to stop breathing, changed color, or became limp. This is a brief resolved unexplained event (BRUE), previously referred to as an apparent life threatening event (ALTE).

Previously, ALTE was defined as: "An episode that is frightening to the observer and 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. ALTE was meant to replace previous terminology, such as “near miss SIDS.”

ALTE was used as the description of an event or a presenting complaint. The potential underlying diagnoses were broad, and ranged from benign to extremely serious. The challenge with the assessment of the patient who experienced an ALTE often was determining via history if the event was in fact a true episode of apnea, cyanosis, or tone change, and to then use the physical examination findings and various diagnostic studies, if needed, to deduce the reason the event took place.

The American Academy of Pediatrics published a clinical practice guideline in 2016 recommending replacing the term apparent life threatening event (ALTE) with the new term brief resolved unexplained event (BRUE).[6]  The goal of this new guideline was to refine the diagnosis to better assess the risk of an underlying serious disorder, and to provide evidence based recommendations on the management of lower risk infants.  In an infant who presented with an ALTE, clinicians often times felt compelled to perform tests and hospitalize the patient even though this may have subjected him to unnecessary risk and was unlikely to lead to a treatable diagnosis or prevent future events. A study conducted in 200 analyzed 243 patients diagnosed with an ALTE on whom 3776 tests were performed. Only 5.9% of these tests contributed to reaching a diagnosis.[7]  

According to the clinical practice guidelines on BRUE, the term should be used when describing an event that occurs in an infant younger than 1 year, when the caregiver reports a sudden, brief, and now resolved (meaning that the patient has returned to it’s baseline state of health) episode of 1 or more of the following:

  • cyanosis or pallor
  • absent, decreased or irregular breathing
  • marked change in tone
  • altered level of consciousness

Where as previously, GERD and feeding issues were the most diagnosed cause for ALTE second to idiopathic, this is no longer the case. If the event is thought to be feeding related (with choking, gagging, or vomiting) the diagnosis should be specific to the feeding issue alone despite the apparent serious reaction it caused in the child. Therefore, there is no indication for a BRUE diagnosis.[8]  

The term BRUE is intended to better reflect the transient nature and lack of clear cause, and removes the “life threatening” label.

Apnea is a symptom that has large possibility of etiologies. In this article, some of the major etiologies of apneic events that an ED physician or primary care physician will encounter are discussed, namely, apnea of prematurity, BRUE, obstructive sleep apnea, and miscellaneous forms of apnea that are toxin mediated, secondary to head trauma, or caused by infections.

Pathophysiology

Apnea refers to a cessation of respiratory airflow and has 3 major types.

Central apnea

Central apnea occurs when there is a lack of respiratory effort due to either a cessation of output from the central respiratory centers or the inability of the efferent peripheral nerves and respiratory muscles required for oxygenation and ventilation to receive or process the signals from the brain. This can be due to immaturity of the system, as seen in certain premature infants, who have a decreased response to hypercapnia (increased carbon dioxide levels). Patients with central apnea have no respiratory effort. This can be seen by a lack of chest wall movement and no breath sounds will be appreciated on auscultation.[9]

Another cause of central apnea is head trauma, as it may interfere with the afferent and efferent signals of the central respiratory center. Head trauma may be the result of abuse and must always be considered in the apneic pediatric patient without an obvious cause. Toxin-mediated apnea is another form of central apnea, as it may cause central nervous system depression and decrease the respiratory drive.

Obstructive apnea

Obstructive apnea, as the name suggests, results from attempts to breathe through an occluded airway. Obstructive sleep apnea (OSA) is the most common form of obstructive apnea in children. Obstructive sleep apnea is on the sleep-disordered breathing (SDB) spectrum. The sleep-disordered breathing spectrum includes snoring, upper airway resistance syndrome, obstructive hypoventilation and, at its extreme, obstructive sleep apnea.

Mixed apnea

Mixed apnea has characteristics of both central apnea and obstructive apnea. Examples can include a patient with a partial obstructive apnea (due to adenotonsillar hypertrophy) who has undergone sedation (causing central apnea), or a premature infant with central apnea who has an obstruction due to nasal congestion brought on by a viral illness. Gastroesophageal reflux is thought to cause this mixed picture as regurgitated gastric contents may occlude the airway and block laryngeal chemoreceptors to send signals for dilation to the brain.

Epidemiology

Frequency

United States

An inverse relationship is found with apnea of prematurity for both birth weight and gestational age. Because advances in NICU care are steadily improving, the number of infants who are surviving ultra-premature births has expanded and therefore the number of children experiencing apnea of prematurity is also growing.  Approximately 70% of babies born before 34 weeks gestation have clinically significant apnea, bradycardia, or oxygen desaturation during their hospital stay.

Prior to the new classification of BRUE, the true incidence of apparent life-threatening event (ALTE) was unknown but was thought to account for 2.3% of hospitalized children, and to occur in between 0.5% and 0.6% of all newborns.[10]  

Since brief resolved unexplained event (BRUE) is a fairly new term having only been described since 2016, there are no reports to describe its epidemiology. In one recent study, BRUEs accounted for approximately 0.6% to 1.7% of all emergency department visits and 7.5% of calls to the emergency medical services system for infants younger than one year of age.[6]

Obstructive sleep apnea (OSA) has been previously shown to occur in almost 2% of the pediatric population, but that number is rapidly increasing secondary to the explosive incidence of obesity in the United States. In older pediatric textbooks, the classic picture of a patient with obstructive sleep apnea was of a patient who was thin and may have even been considered to have failure to thrive. However, currently, the typical patient with obstructive sleep apnea is significantly overweight. Recent evidence now suggests that sleep disordered breathing, which ranges from primary snoring to OSA, is more common among boys than girls, and among children who are heavier than others, with emerging data to suggest a higher prevalence among African Americans.[11]  

There are certain conditions that classically have a high rate of OSA. These conditions include mucopolysaccharidosis, Trisomy 21, craniofacial anomalies, and obesity. Other causes of obstructive apnea are an aspirated foreign body and vocal cord paralysis.

Rosen et al ascertain the prevalence of and risk factors for obstructive sleep apnea syndrome in children with sickle cell anemia. The study concluded that the prevalence of obstructive sleep apnea syndrome in children with sickle cell anemia is higher than in the general pediatric population.[12]

One study has shown that the incidence of apnea can range from 1.2-23.8% in hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis; however, the populations in the studies included premature and neuromuscularly impaired infants.[13]

When assessing apnea in non- RSV viral infections, one study showed that out of 51 apneic infants admitted with bronchiolitis, 13.7% had rhinovirus, while 23.5% had more than one viral infection. Another study analyzed 108 infants with apnea hospitalized at 16 sites spanning 3 winters, and found that apnea risk was similar across the major viral pathogens.[14]  Still, RSV was the predominant virus in 33.3% of infants.[15]

International

Prior to the new BRUE classification, the worldwide incidence of ALTE was unknown. One report from Sweden places the incidence of apnea during the first 4 days of life at 0.35 case per 1,000 population.[16]  Another study from Italy suggests a cumulative incidence of 4.1 per 1,000 live births in the study area.

A Taiwanese population-based cohort study by Chen et al reported that children who are hospitalized due to enterovirus infection were at increased risk for obstructive sleep apnea (adjusted hazard ratio = 1.62, 95% CI: 1.18-2.21, p = 0.003). Allergic rhinitis was an additional factor that increased the risk.[17]

Mortality/Morbidity

As previously discussed, there are different types of apnea, and each has its own unique set of possible causes. The outcome may vary significantly from one cause to another.

Apnea of prematurity frequently persists beyond term gestation in infants delivered at prior to 28 weeks' gestational age. These persistent apnea events may contribute to prolonged hospitalization and mortality. Clearly, if a premature infant with apnea is not taken care of in an appropriate medical setting, the morbidity and mortality can be significant.

The morbidity and mortality rates for the patient who has had a BRUE is difficult to assess. A recent meta-analysis by Brand et al determined that the risk of death after a BRUE is about the same as the baseline risk of death during the first year of life.[7]

Untreated obstructive sleep apnea can result in failure to thrive, cor pulmonale, and loss of intellectual quotient points. In a study performed in first grade children, OSA was found to be disproportionally high in children whose school performance was in the lowest 10% of their class. When children were treated for OSA, they showed significant academic improvement, where as children who did not receive treatment did not improve academically.[18]

Apnea from miscellaneous sources, such an overwhelming sepsis, various infectious agents (RSV, influenza, pertussis, human metapneumovirus), toxic agents, or trauma, all carry very significant morbidity and mortality rates.

Sex

Most studies do not show a gender difference in the incidence of apnea of prematurity.

For BRUEs the male-to-female ratio is variable, but, in some studies, it has been as high as 2:1.

Sleep-disordered breathing continuum, of which OSA is on, appears to have a male predilection. The male to female ratio is estimated to range anywhere from 3:1 to 5:1 in the general population.[19]

Age

The risk for apnea of prematurity is clearly linked to a younger gestational age at birth as well as lower birth weights. Almost all infants born less than 28 weeks’ gestation suffer from apnea. For infants born at 30-31 weeks, the risk is approximately 50%, and, for those born at 32-33 weeks, the risk is about 14%. The risk for those born at 34-35 weeks is 7%.[20]

The typical infant presenting after a BRUE is 8-14 weeks. Approximately 7% of these infants were born prematurely.

OSA can occur at any age; however, its incidence is bimodal. It has its first peak at age 2-6 years and then again later in adulthood.

Infections such as bronchiolitis, classically caused by RSV but also influenza, rhinovirus, human metapneumovirus, or any other viral pathogen can cause apnea. Acquiring the respiratory illness at a younger age puts the patient at much higher risk for apnea.[21]

A bimodal distribution exists for apnea caused by ingestions. Accidental ingestions most commonly occur after children are capable of a pincer grasp, approximately 9 months, until early childhood, whereas both non-accidental ingestions and illicit drug behavior occurs during adolescence.

 

Presentation

History

A detailed history is essential to establish the severity of the apnea episode and to suggest a specific diagnosis.

  • When taking a history, determining how long the actual event lasted may be difficult. Most physicians are familiar with the phenomenon of time expansion in which frightening events seem to last far longer than what actually occurred.
  • The physician may be more successful at determining the timeframe of the incident by asking many details step by step during the history. Repeatedly asking, "what happened next?" may force the person to recollect events in real time as opposed to perceived time. Additionally, using the ambulance record can be extremely helpful. Most ambulance reports will note the time the call came in and the time EMS arrived on the scene. From those times and the report by family and EMS workers, a crude timeframe of events usually can be constructed.

Before discussing the event that brought the patient to the ED, one has to ascertain a history of the child so as to put the event in a context. What is the age of the patient? Was the patient born prematurely? Is there anything in the patient's past medical history, namely, are there any congenital or genetic abnormalities, metabolic disturbances, cardiac conditions, immunodeficiencies, neurological conditions, or is there a history of gastroesophageal reflux disease (GERD)? Is the child on any medications and why? Does the child take any alternative or nonprescribed medications? If the child is still a newborn, learning about prenatal, maternal, and perinatal events is important. Additionally, the physician should find out if such an event has occurred before.

One must also ascertain information about environmental conditions. Where was the child? How was the child found? Who was watching the child? Were there any containers or medicines near the child? Is there anyone in the home who is sick? What time did the event occur? What time of year is it? Is there a combustible motor around?

When assessing the event, it may be best to go through it using a systems-based approach, as follows:

Gastrointestinal- (previously the most likely known cause for ALTEs, second only to idiopathic causes).

  • What does the child eat? Has it been changed recently? If so, why? How soon after feeding did this event occur?
  • Did the patient spit up, vomit, or have food/drink come through his or her nose? Does the child cough during feeds?
  • Was there an arching of the back before and/or during the episode? (This movement is known as Sandifer's posturing and is associated with reflux in infants, but it must be further parsed out to differentiate from posturing from a seizure or acute brain injury.)
  • How much did the child eat? (Try to determine if there is there overfeeding and thus refluxing not secondary to malfunction of the lower esophageal sphincter but to simple overflow of the stomach.)

Neurological

  • Was the child conscious? Was the child shaking? Was the shaking of the entire body or was it focal? Focal seizures have a higher incidence of being associated with an anatomical abnormality than with a generalized seizure.
  • Were there any odd physical movements during the event? What was the body tone of the child?
  • Was there cyanosis? Was there incontinence of the bowel or bladder?
  • Did the child's eyes roll back? Was there drooling or frothing at the mouth?
  • Did the child fall asleep immediately after the event (post-ictal)? How is the child now relative to his or her normal state of behavior? Did the child's behavior stop with stimulation or comforting?

Cardiac

  • How has the child's energy been?
  • Has the child been gaining weight? Is their diaphoresis with feeding? (Feeding may be the most strenuous activity for the newborn, so it is much like a pseudo-stress test.)
  • Did this event occur during increased activity, or did it occur at rest?
  • Was there cyanosis? Was the cyanosis of the extremities, face, or more? (Acrocyanosis of the distal extremities or perioral region may be a normal finding in a newborn. It is often caused by vasomotor changes that result in peripheral vasoconstriction and increased tissue oxygen extraction and is a benign condition). [22]   Outside of the circumstances of the event, is there ever cyanosis?
  • Was the baby's heart beating fast? Did the child have a pulse? Was CPR given? If so, why?

Infection

  • Did the child have a fever?
  • Did the child have rhinorrhea, a cough, or congestion?
  • Was there any vomiting or diarrhea?
  • Was the child breathing comfortably prior to the event?

Metabolic

  • Though much in this section overlaps with other areas, namely, GI, cardiac, and neurological, the questions are repeated here for the reader so that they are understood to have various interpretations.
  • What does the child eat? Has it been changed recently? If so, why? How has the child's energy been? Has the child been gaining weight? Was the child conscious? Was the child shaking? What was the body tone of the child? Was there cyanosis? Was the baby's heart beating fast? Did the child have a pulse? Was CPR given? If so, why?

Behavioral

  • Was this episode part of a tantrum?
  • Did the child scream in frustration, pain, or anger and then hold his or her breath? Has this happened before?

Patients with home monitors

  • In a number of cases, the monitor malfunctioned or was improperly used; however, full evaluation is still warranted. During observation in the ED, the infant should be connected to the home monitor and to one of the cardiorespiratory monitors in the ED for comparison. However, epidemiologic studies have failed to show an effect of cardiorespiratory monitors in reducing the incidence of SIDS in infants presumed to be at risk. [23]
  • Home monitoring devices are simple, single-channel machines that monitor the patient's heart rate and chest-wall movements. Compare the home monitor with the recordings on the equipment in the ED. Newer home monitors have an event-recording feature that allows the episode to be played back.
  • When asking about the event, ask about the child’s behavior and appearance, not just about the numbers on the monitor, to determine if they correlated clinically.
  • Healthy infants may have respiratory pauses as long as 10 seconds. If the episode lasted fewer than 10 seconds and was not associated with vomiting, abnormal movements, hypotonia, or color change, it may be normal.

Physical

As with any physical examination, especially in the emergency care setting, it must begin with the primary survey, ABCDs. This step is crucial in differentiating the sicker patients who may require immediate stabilization. If the child is still having serious respiratory issues, poor perfusion, or a significantly abnormal “D” - disposition, or neurological state - such as abnormal sensorium or with obtundation/unconsciousness, taking control of the airway and obtaining intravenous access may be essential prior to continuing.

  • Vital signs and temperature: All abnormalities must be investigated. If a cardiac abnormality is suggested in the history, 4 limb-blood pressures (BPs) and ECG may be warranted.
  • Height and weight: Deviation from growth charts may suggest child abuse/neglect, congenital abnormalities,  malabsorption, or  inborn errors of metabolism.
  • Head, eyes, ears, nose, and throat examination
  • Abnormal facial appearance, low set ears, micrognathia (undersized jaw), large tongue, and frontal bossing may suggest genetic or metabolic abnormalities.
  • A bulging fontanel suggests raised intracranial pressure, and may be consistent with an infection such as meningitis, or an acute intracranial bleed from accidental or non accidental trauma.
  • Thorough palpation and visual inspection of the cranium should be performed to look for signs of trauma.
  • The physician must look for conjunctival hemorrhages, pupillary abnormalities, and, if possible, retinal hemorrhages (the latter is not pathognomonic for shaken baby syndrome because there can be other known causes, namely glutamic aciduria, but nonetheless it is very highly suggestive of abuse).
  • Rhinorrhea may be suggestive of an infectious etiology.
  • Examination of the tympanic membranes may reveal signs of trauma, hemotympanum, or an infection.  Otitis media is a common cause of fever in a child, and thus a possible source for a febrile seizure.
  • If a finger sweep was performed because of gagging or choking, a thorough mouth/throat examination should be performed because a blind sweep is sometimes associated with intra-oral trauma. [24]

Neck examination

  • Nuchal rigidity is a sign of meningitis, but only approximately 15% of all newborns with bacterial meningitis will exhibit this finding. [25]

Chest examination

  • The examiner should listen for abnormal breath sounds and for heart murmurs or thrills.
  • Chest wall deformities or wide-spaced nipples may suggest genetic disorders.
  • The patient's respiratory pattern should be observed to identify an exaggerated periodic breathing pattern.
  • Retractions and grunting suggest lower-airway pathology.
  • Wheezing with stridor may be consistent with laryngotracheomalacia or bronchitis. Placing the child prone and observing if the sounds resolve is a quick and cheap method of diagnosing laryngotracheomalacia.

Abdominal examination

  • Hepatomegaly or splenomegaly may be signs of hematological, cardiac, metabolic, or congenital abnormalities.
  • Hypo- or hyperactive bowel signs may indicate enteritis, or a toxic ingestion

Musculoskeletal

  • Signs of rickets include (bow legged) or  genu valgum (knocked kneed), craniotabes (soft cranium), costochondral swelling (rickety rosary), or fractures. Significantly low calcium level from rickets can cause seizure activity.

Genital

  • Abnormal genitalia may reflect an endocrinological abnormality.
  • Any sign of trauma should be noted.
  • Neurologic examination
  • Any abnormal neurologic findings should be noted.
  • Specifically, one should look for symmetrical reflexes that are normal in the newborn. Examples include Moro, rooting, grasp, Babinski, and suck reflex
  • There are age-specific reflexes that also expire at certain ages; those should be evaluated for their presence or absence.
  • Seizure activity, muscle rigidity, and abnormal eye movements are important indicators of a neurologic pathology.
  • A sleeping and difficult to arouse child may be a sign of a post-ictal child, a neurologically injured child, a serious infectious cause, a toxic ingestion, or a severe metabolic derangement.

Skin

  • Cyanosis may reflect poor perfusion or hypoxia, depending on the area. Cyanosis to the extremities is not always a concern.
  • Pallor may represent poor perfusion or anemia, or temporary shunt of blood to other areas of the body.
  • Any signs of trauma should be noted.
  • Any sign of needle marks may indicate intravenous or intramuscular use of illicit drugs.
  • Any signs consistent with neurocutaneous disorders (congenital disorders of the ectoderm, which are associated with neurological and cutaneous pathology):

Causes

Gastrointestinal

  • Gastroesophageal reflux ( GER): Apnea due to reflux often may be a mixed apnea with both central and obstructive tendencies. In older patients with GER, apnea is most likely a result from laryngospasm. GER occurs in more than two-thirds of all infants. [26]  It has been noted to cause apnea and hypoxia related to obstruction, laryngospasm and aspiration. Before BRUE, GER was considered to be the most common identifiable etiology of ALTE second only to idiopathic, attributed in 20% to 54% of all patients. [27]
  • A choking episode might have been possible.

Neurological

Increased intracranial pressure: such as the case in congenital hydrocephalus. On exam you would notice a large head circumference, as well as a fixed downward gaze (sundowning) of the eyes.

  • Idiopathic apnea – previously the leading cause of ALTE - The usual cause of apnea is unknown but often presumed to be immaturity of the respiratory center, with a weak respiratory response to hypercapnia.
  • Seizure: Neonatal seizures are often different from those observed in older children thought due to the lack of full myelinization of the peripheral nerves. Although apnea may result from seizures, it is usually not the only symptom. Most patients with seizures also have abnormal movements or posturing, and lateralizing eye movements. In past studies, 10-11% of patients with recurrent ALTE were found to have epilepsy. [28]
  • Head injury causing central apnea
  • Toxin-related central apnea: Certain drugs are known to cause respiratory depression (opiates, benzodiazepines, and barbiturates) and thus place the patient at risk for central apnea; however, in most pediatric apnea cases, the patient has no history of drug exposure. The examining physician should ask about the mother's use of medications, particularly if the infant is being breastfed.  Carbon monoxide poisoning must also be considered because it is more likely to affect young infants (because of CO greater affinity for fetal hemoglobin) more than adults.

    See the list below:

    • One recent study has shown that in utero exposure to nicotine smoke has a negative effect on the chemoreceptors responsible for respiratory drive and may increase the risk of insufficient response to respiratory challenges during sleep. [29]  This was confirmed when patients with suspected apnea were found to have less spontaneous arousals during sleep, especially when exposed to second-hand smoke. [29]
  • In older infants, breath holding spells may cause apnea. A breath holding spell is usually triggered by an inciting event, namely frustration, surprise, anger or fear. The infant usually cries, followed by a pause, and then becomes pale or blue. Occasionally, a breath holding spell can lead to loss of consciousness and the infant will become limp. Breath holding spells are self-limiting and do not put the infant in danger. There is no treatment for a breath holding spell- because it is self limited and benign. Supportive care is all that is needed. However, there needs to be significant education and reassurance given to the family. Breath holding spells can begin as early as 6 months of age, and are usually outgrown by mid-childhood. [27]  

Respiratory

  • Upper/lower respiratory infection either due to RSV, or other infections ( pertussis, influenza, human metapneumovirus, rhinovirus, or other respiratory pathogens) is the second most used discharge diagnosis for patients who initially present with apnea or suspected BRUE. [27] ]
  • Aspiration pneumonia may cause apnea of a mixed or obstructive picture and may have a GI, neurological, or a respiratory etiology.

Infectious

  • Upper/lower Apnea may be the presenting symptom for sepsis, or a serious bacterial infection (SBI). Previous studies have shown that the incidence of SBI presenting with ALTE is approximately 0-3%. [30, 31]

Cardiac

  • Primary arrhythmia: Cardiac arrhythmias can cause central apnea by disrupting the perfusion of the brain and lungs. Infants with previous cardiac surgery or known congenital defects near the conducting system may have an arrhythmia. In most cases, the cause is obscure. The infant presenting with BRUE, who ultimately has a cardiac cause, is less likely than others to present with primary apnea alone.
  • Congenital heart disease may present with cyanosis, hypoxia, and/or seizure.
  • The 5  T s of pediatric cardiac congenital malformations are as follows:

    See the list below:

    • Tetralogy of Fallot
    • Transposition of the great vessels
    • Truncus arteriosus
    • Total anomalous pulmonary venous return
    • Tricuspid atresia

Other potential causes

In an ill-appearing infant, apnea may have many potential causes, including the following:

  • Infection (eg, sepsis, meningitis, bronchiolitis, infant botulism)
  • Dehydration or renal tubular acidosis
  • Child abuse, including physical abuse, Munchausen syndrome by proxy, and aborted infanticide.
  • Abuse should be considered when infants do not appear well on arrival. Careful physical examination should be performed to look for physical signs of abuse. Some of these physical exam findings include but are not limited to: retinal or subconjunctival hemorrhages, unexplained facial injuries such as a torn frenulum in the non ambulatory child, bruising in non ambulatory infants or bruising in unusual locations such as behind the ear or neck, under the chin, on the torso or buttocks, unexplained human bite marks, or unexplained burns.
  • Munchausen syndrome by proxy may be suspected in the infant who has an atypical history relating to the apnea, particularly when the family has been to several EDs and/or physicians with the same complaint and when "no one can find the cause." A previous SIDS death in the family also increases the risk of Munchausen by proxy. Although not found in all cases, family dynamics may include a father who is somewhat distant or uninvolved and a mother (usually the perpetrator) who has a healthcare background and who seems to identify with members of the healthcare team.
  • Home monitor alarm: Causes may include true apnea, but more commonly technical errors such as worn or faulty leads, improper placement of leads, a damaged monitor, failure to adjust the limits of the alarm to account for a decreasing normal pulse and respiratory rate as the infant ages, or non compliance with monitoring. [23]
 

DDx

 

Workup

Laboratory Studies

According to the AAP Clinical Practice Guidelines, BRUE is a diagnosis of exclusion, and should be applied when there is no apparent etiology after performing an appropriate history and physical. Lower-risk infants should not undergo routine diagnostic testing, and should not be admitted solely for cardio-respiratory monitoring. Higher risk infants are more likely to benefit from diagnostic testing and admissions. History and physical should guide the clinician. 

If the infant is truly afebrile and appears well, laboratory results are likely to be within the reference ranges. In a study looking at patients who presented with apparent life-threatening events (ALTEs), it was demonstrated that only 5.9% came up with a diagnosis with positive testing after a non-contributory history and physical exam.[7]

  • If the infant does not appear well, the following studies should be considered:
  • Rapid bedside glucose testing, as a decreased glucose level may indicate sepsis or a metabolic derangement. Hypoglycemia can be treated quickly, and if untreated, its consequences can be severely damaging. Therefore, early diagnosis is essential.
  • Complete blood count with differential
  • Blood culture
  • Complete metabolic panel: The combination of  hyperkalemia and  hyponatremia may be the first suggestion of congenital adrenal hyperplasia in the male infant.
  • Arterial blood gas (ABG) or venous blood gas (VBG) measurement
  • Lumbar puncture with culture
  • Urinalysis and urine culture via catheter to obtain the cleanest specimen

Additional studies may include the following:

  • Viral respiratory panel to look for common causes of bronchiolitis such as RSV or  influenza.
  • The tests listed above help in identifying unexplained metabolic acidosis, potential sepsis, or unexplained anemia.
  • When the clinical presentation warrants, tests of the carboxyhemoglobin and methemoglobin level and screening for certain toxins (eg, opiates, benzodiazepines, barbiturates, marijuana, toxic alcohols, botulism) should be considered.

Imaging Studies

See the list below:

  • In most cases, no imaging studies are needed.
  • In those cases, in which raised intracranial pressure or intracranial injury or hemorrhage due to abusive mechanisms is suspected, CT scanning of the head is suggested as a first line modality; MRI may be more useful for follow up imaging. [32]
  • In hospitalized premature infants, US of the head may reveal intraventricular and periventricular hemorrhages. [33]
  • When child abuse is seriously considered, a skeletal survey should be performed.
  • Chest radiography should be performed in the presence of increased respiratory rate or abnormal findings on lung examination
  • Echocardiogram should be performed in the case of murmur heard on auscultation, or with a history of concerning for a cardiac etiology such as cyanosis or sweating with feeding.

Other Tests

See the list below:

  • A neurologist may request an EEG
  • ECG to assess for cardiac arrhythmias or cor pulmonale
  • If congenital adrenal hypoplasia is being considered, cortisol and thyroid levels
  • Fiberoptic evaluation of the larynx if tracheomalacia or laryngomalacia is suspected
 

Treatment

Prehospital Care

See the list below:

  • Prehospital care first and foremost includes resuscitation, if necessary, and prompt monitored transport to an ED.
  • If the child is cyanotic or a pulse oxygen level is low but respiratory effort is present, O 2 should be administered via a nonrebreather.
  • If the infant has an apneic event during transport, prehospital personnel should first attempt simple manual stimulation of the infant with brisk rubbing along the patient's back, patting, or gentle thumping of the feet. If these maneuvers fail, resuscitation via bag valve mask should be initiated immediately and securing a  laryngeal mask airway (LMA) or endotracheal tube (ETT) placement may be considered if a long transport time is foreseen, the apneic event is prolonged, or hypoventilation or poor respiratory effort follows.
  • If the patient is seizing, local protocols should be followed and oxygen administered.
  • If the patient is lethargic, local protocols should be followed, but, if a glucose evaluation can be performed, it should be, and hypoglycemia treated if present. If not possible, dextrose should be given prophylactically.
  • With the cyanotic child or a child with an abnormal cardiac rhythm, an AED should be placed or an ECG should be obtained. If the child is pulseless,  CPR should be initiated and epinephrine given.

Emergency Department Care

See the list below:

  • In the ED, all infants should receive cardiac and respiratory monitoring.
  • Ill-appearing infants should be treated as needed on the basis of their clinical condition. Treatment may include fluid resuscitation and aggressive antibiotic treatment of sepsis.
  • Well-appearing infants may need no emergency treatment other than a careful history and physical examination and then some close observation.
  • The 2016 American Academy of Pediatrics Clinical Practice Guidelines on BRUE aim to standardize the approach to evaluation and management that is based on the risk that the infant will have a repeat event or has a serious underlying disorder. An infant is determined to be either low risk or high risk based on presentation, and work up and management should be performed accordingly. [34]  
  • A feeding should be observed in the health care setting for poor feeding techniques as well as for infant feeding difficulties.

Consultations

The history, physical examination, and diagnostic workup determine which consultation may become necessary to evaluate the patient. These may include the following:

  • Pediatric gastroenterologist
  • Pediatric neurologist
  • Pediatric cardiologist
  • Pediatric endocrinologist
  • Metabolic/genetics specialist
  • Pediatric intensivist
  • Neonatologist
  • Sleep specialists
  • Otolaryngologist

The patients who are on home monitoring should have a consultation with the service that placed them on the monitor. Most children with apnea receive follow-up care by a special apnea service.

  • Such services may be helpful by providing important data about the patient's history. Also, they often facilitate contact with the company providing the monitoring service.
  • In addition, the apnea service may be able to simplify the process of admission or transfer to a tertiary care pediatric facility.
 

Medication

Medication Summary

Caffeine citrate is currently the medication used in NICUs to treat apnea of prematurity (AOP). The specific mechanism is not known, but caffeine citrate has been shown to act as a respiratory stimulant and allow infants to overcome the developmental immaturity that causes apnea or periodic breathing.[35]

Unfortunately, patients with AOP have demonstrated various responses. A recent study has identified genetic markers (adenosine receptor gene polymorphisms) that may be able to predict an individual’s response to caffeine.[36]

A recent study by Alansari et al aimed to determine the effectiveness of caffeine used for the treatment of apnea associated with bronchiolitis. It consisted of 90 infants diagnosed with viral bronchiolitis associated with apnea. It was found that unlike in AOP, a single dose of caffeine citrate did not significantly reduce apnea episodes associated with bronchiolitis.[37]

 

Follow-up

Further Outpatient Care

Children may be safely discharged for further outpatient care if one of the following conditions exist:

  • The history is consistent with a breath holding spell and the physical examination findings are normal.
  • The history is consistent with periodic breathing and the physical examination findings are normal.
  • The history suggests an isolated choking episode from either GERD or overfeeding and the physical examination findings are normal. The patient also then feeds normally in the ED.
  • The history is consistent with a simple febrile seizure and the physical examination findings are normal.
  • An unequivocal problem with a home monitor occurred.
  • When choking is suspected in an infant who feeds aggressively, the parents should be instructed to frequently interrupt feeding and to burp the infant more often than before.

If obstructive sleep apnea (OSA) is diagnosed, the patient should have an outpatient sleep study and follow up with an otolaryngologist. If the episodes of OSA are very prolonged and significant, an EKG should be performed in the ED to rule out right heart strain or cor pulmonale.

Further Emergency Department Care

If it is determined that a patient had a low risk brief resolved unexplained event, it is not recommended to perform any further testing other than testing for pertussis (if a respiratory infection is suspected) or an electrocardiogram. The infant should be monitored for 1-4 hours in the emergency department with continuous pulse oximetry and serial observations ensuring that vital signs, physical examination and symptomatology remain stable. The infant should be assessed for social risk factors of child abuse; and clinicians should offer resources for CPR training and education regarding brief resolved unexplained events.[27]

Treatment of sleep apnea in children includes both surgical and medical approaches. When adenoid and tonsillar hypertrophy accompany the OSA, adenotonsillectomy (surgical removal of adenoids and tonsils) is the treatment of choice. For those that are not suitable candidates for surgery or have symptoms despite surgery, the most effective treatment in both adults and children, is continuous positive airway pressure (CPAP). One study has shown that warm humidified air delivered through an open nasal cannula actually decreased the occurrence of sleep apnea episodes in children with OSA.[38]

For more information on pediatric sleep apnea, please refer to the Medscape Reference Pediatrics article Sleep Apnea.

Transfer

Most infants who have a true apneic event should be evaluated at a facility with diverse faculty and expertise in the diagnostic evaluation of such unique pediatric events.

The team that is transporting the infant should be capable of monitoring and, if necessary, resuscitating an infant. If available, a pediatric transport team is preferred.

Complications

Because the etiologies are so variable, the complication relate to the specific cause of the apnea. These are mostly addressed in Mortality/Morbidity.

One complication that is often ignored is the psychological impact of home monitoring on the family.

  • Monitoring places a tremendous amount of pressure on the caretakers. Families deal with these pressures in many ways.
  • Some parents eventually stop using the monitor, whereas others become dependent on it.
  • Some families experience renewed fears when they are told that their child no longer requires home monitoring.
  • Many of these stressors may be manifested in the ED.
  • Parents of a child for whom home monitor is being discontinued may present to the ED with a complaint of frequent alarms to try to continue monitoring.

Prognosis

The prognosis is case specific.

In general, as the child matures, the cause of the suspected brief resolved unexplained event (BRUE) is diagnosed and treated or spontaneously resolves. If the apnea is determined to be idiopathic, the prognosis is generally excellent.

Patient Education

See the list below:

  • Parents of infants who are discharged should be instructed to return if more episodes occur, if episodes become associated with color change, or if new and/or worrisome findings (eg, fever, lethargy, frequent vomiting) develop.
  • Infants who have had a choking episode should receive feeding instructions as described above.
  • Families of monitored infants should be reminded to maintain current CPR training.

Patient Education

See the list below:

  • Parents of infants who are discharged should be instructed to return if more episodes occur, if episodes become associated with color change, or if new and/or worrisome findings (eg, fever, lethargy, frequent vomiting) develop.

  • Infants who have had a choking episode should receive feeding instructions as described above.

  • Families of monitored infants should be reminded to maintain current CPR training.

  • For patient education resources, see the Children's Health Center, as well as Sudden Infant Death Syndrome (SIDS).