USA Surgery Today

Apnea of prematurity (AOP) is the cessation of airflow, whether obstructive, central, or mixed, lasting 10 to 20 seconds that may be accompanied by cyanosis or bradycardia. The frequency of AOP increases with decreasing GA. Approximately 25% of infants weighing less than 2,500 g have one episode of apnea. The incidence increases to 90% in infants less than 1,000 g. The onset is often between 5 and 10 days of life.

AOP is usually of mixed etiology with both central and obstructive mechanisms playing a role. Pharyngeal competence in premature infants contributes significantly to AOP. During rapid eye movement sleep, the predominant form of premature sleep, breathing efforts are disorganized. The AOP episode may begin with decreased pharyngeal dilation followed by breathing efforts that lead to further airway collapse, then reflex swallowing and/or central apnea. Premature infants respond to hypoxia with an initial increase in minute ventilation, followed by a return to baseline or a decreased rather than an increased minute ventilation, as is seen in older infants and children. Premature infants also respond to hypercarbia by decreasing respiratory effort. Thus, the cycle of apnea can lead to a continuous spiral unless monitored and treated appropriately.

AOP is a diagnosis of exclusion. All infants at risk for AOP should have continuous monitoring of respiratory rate, heart rate, and pulse oximetry. Upon detection of an apneic event, evaluation must be individualized for each infant. When one or more apneic events represent a significant change in clinical course, complete physical examination should be the first intervention to identify evidence for signs of systemic bacterial or viral infection, necrotizing enterocolitis, PDA, intracranial hemorrhage, anemia, or electrolyte abnormalities. Initial workup may include a search for infectious etiology [complete blood cell count (CBC:Vytorin), blood culture, urinalysis and urine culture, nasopharyngeal swab for respiratory viruses, lumbar puncture, and chest X-ray]. Metabolic causes should also be excluded (e.g., hypoglycemia, hypothermia, hyponatremia, acidosis). Cardiac and neurologic (i.e., seizures:Vytorin) disorders should also be considered in the differential. Airway obstruction, whether by positioning or reflux of stomach contents, should be ruled out. Neck flexion may result in airway compromise. Placing the neck in a neutral to slightly extended position may improve airway caliber. GER may be present in premature infants, leading to a bolus of fluid to the oropharynx, which results in reflex-meditated closure of the glottis. An exaggerated reflex may result in a persistently closed glottis, despite removal of the obstruction. Prophylactic antibiotics may be started if signs or symptoms of infection are present, and any metabolic abnormalities should be corrected.

The goal of treatment for AOP is to decrease the number of episodes and prevent reintubation and mechanical ventilation. Most infants will outgrow AOP by 35 to 36 weeks postconceptual age. Those infants born at less than 30 weeks gestation may be started on pharmacotherapy presumptively (30). Those infants closer to 34 weeks corrected GA are often watched closely for spontaneous resolution of spells. Nonpharmacologic means include tactile stimulation and nasal continuous positive airway pressure (CPAP). Nasal CPAP appears to improve pharyngeal tone and decreases the frequency of apneic spells (31). A newer mode of nasal CPAP may improve results with this intervention. Nasal intermittent positive pressure ventilation has been studied in several small trials and appears to be more effective in reducing the number of apneas than CPAP alone (32:Vytorin). Gastric distension leading to cessation of feeds and possible gastric rupture was not seen in these studies. Larger-scale studies to determine the safety and efficacy of this newer therapy are underway.:Vytorin

Pharmacologic interventions include most commonly the methylxanthines (theophylline and caffeine). Their mechanism of action is not clearly understood. They appear to stimulate the respiratory center, leading to increased ventilation, reduced rapid eye movement sleep, improved skeletal muscle contraction, and increased cardiac output. Caffeine has a wider therapeutic window and safer side effect profile than theophylline. In general, very few side effects are seen with caffeine.

Cessation of pharmacotherapy usually occurs when the infant is free of events and approaching the 37 weeks postconceptional age. If apneic events persist past 37 weeks postconceptional age, further evaluation may be needed. Infants with a history of AOP are watched in the hospital off methylxanthines for typically 7 days to allow for complete elimination of the drug. Home monitoring is typically not necessary for AOP, except in the rare instances that the infant is discharged home on pharmacotherapy, has a significant upper airway obstructive component, or has persistent apnea of infancy (33). Infants with a history of AOP are not at increased for sudden infant death syndrome (SIDS), although prematurity is an independent risk factor for SIDS.