APNEA OF PREMATURITY
Apnea of prematurity (AOP) is a common clinical problem affecting premature infants and is related to developmental immaturity. By definition, it is the cessation of breathing for more than 15 to 20 seconds accompanied by bradycardia (heart rate less than 80 beats/min) and desaturations (SpO2 less than 80%; Zhao, Gonzales, & Mu, 2011). AOP is inversely related to gestational age (Eichenwald & American Academy of Pediatrics Committee on Fetus and Newborn, 2016). The majority of infants with less than 1,000 g birth weight and less than 28 weeks gestational age at birth develop AOP (Morton & Smith, 2016). It is rarely experienced by infants born at greater than 37 weeks postmenstrual age (Fairchild et al., 2016). Neonatal intensive care unit (NICU) nurses are at the forefront of managing infants with AOP.
Apnea is classified as central, obstructive, or mixed. Central apnea is the complete termination of respirations that occurs because of the immaturity of the brainstem and resultant poor control of the central respiratory drive. Obstructive apnea occurs when there is no airflow within the upper airway, particularly at the level of the pharynx, while the infant continues to have respiratory effort. Mixed apnea involves an event of central apnea that is directly followed by or preceded by an obstructive apnea event. The majority of premature infants experience mixed apnea, which occurs as an episode of apnea and bradycardia with desaturation. AOP needs to be distinguished from periodic breathing in which pauses in respiration last for as long as 20 seconds and alternate with breathing. Newborns of all gestational ages have periodic breathing that is a normal variant of respiration in the neonate. However, if the respiratory pause lasts more than 20 seconds, it is considered apnea and requires ongoing observation and may require treatment.
Due to the immaturity of the respiratory system, premature infants have an altered response to hypoxia and hypercapnia. In response to hypoxia, infants experience ventilatory depression that is a transient increase in respiratory rate followed by a decrease in spontaneous respirations below the infant’s baseline respiratory rate. This pattern may recur over several weeks. Various neurotransmitters are involved in hypoxic ventilatory depression. In response to hypercapnia, premature infants have a decreased respiratory rate and prolonged exhalation unlike adults, who increase their respiratory rate when hypercapnic (Darnall, 2010). Hypercapnic ventilatory response is mediated primarily by central chemoreceptors.
126The laryngeal chemoreflex is involved in the control of breathing. This reflex protects the lungs from aspiration. However, in the premature infant, an exaggerated response to stimulation of the laryngeal mucosa can lead to apnea, bradycardia, and hypotension. The passage of a feeding tube or vigorous suctioning of an infant are examples of stimulation that can trigger a bradycardic episode, followed by apnea. As infants mature, the laryngeal chemoreflex matures to respond more often by coughing and less often by apnea and swallowing (Thach, 2007). This laryngeal chemoreflex is mediated through superior laryngeal nerve afferents.
Although AOP is primarily attributed to physiologic immaturity, other factors may contribute. Functional residual capacity (the air left in the lung after an exhalation) is decreased because of pulmonary immaturity and increased chest wall compliance. This results in increased work of breathing for the infant, the development of diaphragmatic fatigue, and apnea. Apnea occurs more often during rapid eye movement (REM) sleep when infants have more paradoxical breathing than during quiet sleep. The mechanism of sucking, swallowing, breathing, and esophageal function is complex and requires physiologic maturity lacking in premature infants (Lau, 2015). Premature infants have difficulty coordinating this process with resultant apneic episodes during feeds.
Infants are traditionally obligate nose breathers. Irritation of the mucus membranes from a nasogastric tube and frequent suctioning of the nares contributes to swelling of the mucus membranes of the nasal passages with resultant obstruction of the nares. This, in turn, may cause apnea.
AOP may be idiopathic. However, it is also a symptom of multiple pathologic conditions in the infant, including infection, intraventricular hemorrhage, seizures, electrolyte imbalance, inborn errors of metabolism, congestive heart failure, patent ductus arteriosus, anemia, necrotizing enterocolitis, and temperature instability. The association between gastroesophageal reflux (GER) and AOP is controversial. Although there is a temporal relationship, cause and effect has not been established.
In premature infants, pathologic conditions may present concurrent with apnea, cyanosis or pallor, and hypotonia and this is called secondary apnea. It is critical that the evaluation of an infant occurs in a timely manner, whether an infant develops apnea or has increased apneic events.
In addition to the physical evaluation, it is important to read both the mother’s and the infant’s birth history to determine if there are any factors that predispose to apnea. A complete blood count (CBC) and C-reactive protein (CRP) assess for infection and anemia. A lumbar puncture may be necessary if the infant’s history and current condition clinically indicate it. Electrolytes should be evaluated to assess for possible metabolic causes. A head ultrasound (HUS) may 127be needed to rule out intraventricular hemorrhage (IVH). A chest x-ray is done to assess respiratory and cardiac status.
NURSING INTERVENTIONS, MANAGEMENT, AND IMPLICATIONS
The nurse at the bedside is instrumental in the care of the infants with AOP. Cardiorespiratory and pulse oximetry monitors assist the nurse in monitoring apneic events. Documentation of apnea, bradycardia, and desaturation episodes is paramount. The nurse needs to document any event that occurs before the apnea; the length of the apnea; if the apnea is associated with bradycardia, including how low the heart rate falls; if a desaturation occurred, how low the desaturation fell, as well as how long the desaturation lasted; any change in color; what intervention the nurse performed; and the infant’s response to that intervention. Infants usually respond to gentle stimulation if they become apneic. In the event that the infant does not respond to the stimulation, the nurse needs to initiate bag-and-mask ventilation.
Positioning of the infant is extremely important. The nurse must assess the infant’s alignment and keep the head at midline without extension or flexion of the neck. Term and healthy preterm infants should be placed supine, but it is not known if preterm infants may benefit from prone or side-lying positions to help decreased apneic events (Bredemeyer & Foster, 2012).
Keeping premature infants in a neutral thermal environment is a basic tenet of neonatal nursing. Rapid changes in temperature have resulted in apneic events in infants (Gardner, Carter, Enzman Hines, & Hernández, 2016). Keeping an infant in the lower end of the neutral thermal environment, rather than the upper end, may help decrease the number of apneic events.
Respiratory support is commonly required. A number of noninvasive support measures, including high-flow nasal cannula, synchronized nasal intermittent positive-pressure ventilation (SNIPPV), nasal bi-level positive airway pressure (N-BiPAP), nasal continuous positive airway pressure (CPAP), and bubble CPAP may be required for an infant who does not respond to gentle stimulation or bag-and-mask ventilation. Sicker infants may require mechanical ventilation.
Medications are commonly used. Methylxanthines, such as caffeine citrate, aminophylline, and theophylline are pharmacologic treatment modalities for AOP. Caffeine citrate is preferred because it requires only daily dosing, has a longer half-life, and a wider therapeutic index. Nurses should give caffeine in the morning to prevent disruption of sleep–wake patterns. Nurses need to be cognizant of the side effects of caffeine citrate therapy, such as jitteriness, tachycardia, and feeding intolerance. Doxapram is another medication that has been used for the treatment of AOP for over four decades in Europe, but is not used in the premature infant population in the United States because it contains benzyl alcohol.
Anemia may play a role in AOP. Increase in apneic events may occur at the time the premature infant’s hemoglobin has fallen to its physiologic nadir. Treatment for AOP with packed red blood cell transfusions is controversial. Blood transfusions are usually reserved for infants with severe anemia who are having multiple apneic events daily.
Nurses play a critical role in the prevention and treatment of AOP. The sophisticated monitoring equipment available today alerts nurses when an infant’s status is changing, but medical device alarm safety is a major patient safety issue. The majority of the equipment used in the hospital has some type of alarm system. Because of the number of false alarms triggered, nurses, as well as all members of the health care team, have become sensory overloaded and desensitized. This is known as alarm fatigue (Sendelbach & Funk, 2013). As a result, health care team members may ignore, override, or turn off alarms (Tanner, 2013). Alarm fatigue has resulted in avoidable deaths. Most NICUs have set parameters for cardiorespiratory and pulse oximetry monitors. However, education needs to be ongoing to ensure safe patient care.
AOP is a common clinical problem and reflects physiologic immaturity. Current treatment modalities include xanthine therapy and noninvasive ventilator support. As infants mature, the number of apneic events and the interval between apneic events should be decreased in order to discharge the infant home safely. Parents need extensive education, including infant CPR. Close, accurate monitoring and documentation of all apneic events are an important component of infant care and the ultimate responsibility of the bedside nurse.
Bredemeyer, S., & Foster, J. (2012). Body positioning for spontaneously breathing preterm infants with apnoea. Cochrane Database of Systematic Reviews, 2012(6), Art. No.: CD004951. doi:10.1002/14651858.CD004951.pub2
Darnall, R. A. (2010). The role of CO2 and central chemoreception in the control of breathing in the fetus and the neonate. Respiratory Physiology and Neurobiology, 173(3), 201–212. doi:10.1016/j.resp.2010.04.009
Eichenwald, E. C., & American Academy of Pediatrics Committee on Fetus and Newborn. (2016). Apnea of prematurity. Pediatrics, 137(1), e20153757. doi:10.1542/peds.2015-3757
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