Infants are often brought for urgent or emergent medical assessment owing to abnormal breathing patterns or worrisome respiratory episodes. Often the episode resolves before the patient arrives for initial evaluation and does not recur. However, some infants with respiratory episodes have significant underlying medical conditions or even life-threatening events. Many infants with both types of episodes are hospitalized for monitoring, diagnostic testing, and management despite a stable appearance at presentation, while others are able to be managed as outpatients. There is wide variation in the evaluation and management of these episodes. This chapter addresses presentations suggestive of apparent life-threatening events (ALTEs) and briefly discusses central apnea of neonates and young infants. It also examines pediatric obstructive sleep apnea.

Apparent life-threatening event (ALTE) refers to a complex set of symptoms that presents unexpectedly in an infant, are of concern to the observer, and cannot be easily characterized by the healthcare provider.^1,2 Approximately 1% of infants have an ALTE which prompts admission. The most common age at presentation ranges from 6 to 10 weeks.^3-7 Many other events may occur during infancy, yet not be appreciated or raise concern for the caregiver. For example, in one large longitudinal cohort study of infants on home cardiorespiratory monitors, 43% of healthy term infants had at least one 20-second apneic episode over a 3-month period.⁸ In a separate study, over 5% of parents recalled seeing an apnea of that duration.⁷ The pediatric hospitalist may be asked to clarify the features of the presentation, stabilize the infant, and reassure the caregivers. If admission is considered, the hospitalist must diagnose and treat the precipitating cause (if one is determined), educate the caregivers, and render a disposition.

BACKGROUND

In September 1986, the National Institutes of Health (NIH) convened an expert panel to review the literature and discuss the relationship of infantile apnea, ALTE, and sudden infant death syndrome (SIDS). These experts standardized the definition of ALTE by describing it 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.” NIH also proposed eliminating the terms “near miss SIDS” and “aborted crib death” because no causal link could be found between ALTE and SIDS.¹ The relationship among ALTE, infant apnea, and SIDS is still unclear, and there is increasing evidence that these disorders are unrelated.^3,8,9

Owing to the breadth of the definition, ALTE has been attributed to everything from normal physiologic events to life-threatening illnesses.^5,10,11 Therefore, it must be stressed that the symptoms of ALTE may represent a normal physiologic occurrence and be of no clinical significance. Although most ALTEs are benign, healthcare providers must be able to distinguish events that are frightening, potentially clinically significant, and truly life threatening.

PATHOPHYSIOLOGY AND CLINICAL PRESENTATION

The potential underlying abnormalities of ALTE are myriad; therefore the pathophysiology depends on the underlying condition. A partial listing of diagnoses is provided in Table 140-1, and a detailed discussion of the pathophysiology for each condition is found within the corresponding section of this text.

Pathologic apnea is defined as an event associated with physiologic compromise, as indicated by changes in oxygenation, color, muscle tone, or bradycardia. Apneic events may be obstructive, central, or mixed. Obstructive apnea, even of brief duration (6 seconds or 2 breaths), is considered abnormal.¹² Central respiratory pauses are generally considered abnormal when they last 20 to 30 seconds or longer.^8,12 Shorter central apneic episodes (6 seconds or 2 breaths) are considered abnormal when they are accompanied by physiologic compromise.¹² Mixed apnea combines the features of central and obstructive episodes in the same respiratory event (usually defined by an epoch of time).¹² Central apnea results from the lack of brainstem-mediated respiratory effort, as can be seen in premature infants. Obstructive apnea results from attempts to breathe against a blocked airway, as can be seen in laryngomalacia or adenotonsillar hypertrophy.

Color changes result from decreased oxygenation or differential blood flow to a portion of the body. Transient plethora may result from hyperemia and localized vasodilation (often venous), whereas pallor may result from vasoconstriction. Both tend to be mediated by autonomic activity. Cyanosis is a consequence of hemoglobin desaturation and can result from impaired oxygen exchange or distribution. Differentiating the ruddy appearance of plethora from cyanosis is often difficult and can result in confusion for the caregiver and healthcare provider. Central cyanosis is most reliably identified by blue or purple discoloration or darkening of the lips or tongue. Acrocyanosis and circumoral cyanosis are not necessarily signs of a central cyanotic state or abnormal gas exchange. Acrocyanosis in newborns is common and may be due to vasomotor instability or vasoconstriction due to heat-retention efforts. Circumoral cyanosis often presents as a circular blue or purple discoloration in the perioral area, not involving the lips or tongue. It is more easily recognized in fair-skinned infants, especially with crying, breath holding, or other Valsalva-type efforts. It is likely related to congestion of the superficial venous plexus in this region.

Altered muscle tone may result from neuronal activity that is centrally or peripherally mediated, as can be seen in seizures or clonus. Choking results in impaired respiration from compression or obstruction of the larynx or trachea. Choking may be due to laryngospasm, bronchospasm, regurgitation of gastric contents, or aspiration of a foreign body. Gagging or retching is manifest by the emetic center located in the medulla; triggers by various neural pathways along the digestive tract, heart, testicles, and chemoreceptor trigger zone. The response is a spasmodic contraction of the diaphragm and intercostal muscles combined with the closure of the glottis.¹³

DIFFERENTIAL DIAGNOSIS

Because ALTE is a description rather than a diagnosis, the hospitalist must consider the underlying cause (see Table 140-1). Many of the diagnoses associated with ALTE are easy to differentiate on the basis of history and physical examination. For example, an infant presenting with an ALTE manifest by obstructive apnea and cyanosis in the context of congestion, cough, and gagging and lower respiratory wheeze would likely be diagnosed with a viral bronchiolitis infection.^14,15 Interestingly, both central (especially in newborns) and obstructive events can be observed with respiratory syncytial virus (RSV) infection.^16,17 An ALTE in an infant with choking and gagging in association with feeding or regurgitation likely represents underlying dysphagia or gastroesophageal reflux (GER).^10,18 An ALTE in an infant associated with respiratory irregularity and abnormal repetitive musculoskeletal movements likely represents a seizure.^10,19,20

Other cases are less well defined than these examples and present challenges to the practitioner who must evaluate and manage the patient. The sudden, irreproducible nature of the event may make coordinating the investigation difficult. Often, the history is incomplete or inaccurate because the caregiver is distracted by fear or medically naive. In addition, the infant may appear normal on examination. Clinical judgment must guide the evaluation and eventual disposition.

EVALUATION AND DIAGNOSIS

A thorough history from the primary witness or witnesses and a careful physical examination will guide the practitioner’s assessment (Table 140-2). Indeed, both the history and the exam should be individually tailored and specific enough to provide some physiologically rational explanation for the course of events. Despite the level of concern or severity of the event, the cause can often be determined as a physiologic response such as an isolated choking episode or acrocyanosis. In the event that a reasonable explanation cannot be provided, the investigation can often be directed based on some risk stratification. Characteristics of the patient or presentation that confers greater risk of an underlying progressive diagnosis or recurrence include residual signs on exam, a prior history of ALTE, clustered events, prematurity (lessening after 48 weeks postconception), or features of non-accidental trauma.^11,21-29

There is no minimum or maximum number of required tests.^29,30 First, the sheer number of possible tests makes the detection of some abnormality likely. The result may be nonspecific or spurious. It may also mislead the practitioner into making a diagnosis that is coexistent but not causative³¹ (see Table 140-3). Next, because ALTE describes a presentation rather than a diagnosis, the workup should be directed at the suspected condition rather than following a nonspecific algorithm. Finally, testing helps in <15% of cases when the history and physical exam are negative.³¹ Therefore, in patients with no symptoms or exam findings that can direct the evaluation, the provider must balance the invasiveness and cost of the test with the potential harm that could occur from missing or delaying a diagnosis. Patients for whom trauma could be a cause should get imaging, especially since up to 5% can present without physical exam findings of concern.²² Features that are associated with greater risk of abusive head trauma include suspicious physical findings, retinal hemorrhages, discrepancy in the clinical history, parents calling emergency services, and the presence of vomiting or irritability at the time of presentation.²⁶ In an infant presenting with an ALTE while on a home cardiorespiratory monitor or because of frequent alarms, expedited monitor download should be conducted to determine whether true apnea or bradycardia occurred.^8,9,32