Apnea of prematurity, or the cessation of breathing, is seen commonly in infants less than 37 weeks’ postmenstrual age (PMA). The literature clearly defines clinically significant apnea in infants as breathing pauses that last for >20 seconds or for >10 seconds if associated with bradycardia (heart rate less than 80 beats/min) or oxygen desaturation (<80–85% by pulse oximetry) (Committee on Fetus and Newborn, 2003). Apnea of prematurity occurs in over 50% of premature infants and in the majority of infants who are less than 1,000 g at birth (Alden et al., 1972). It has been associated with sepsis, intracranial hemorrhage, vaccine administration (Klein et al., 2008), and severe hyperbilirubinemia (Amin, Charafeddine, & Guillet, 2005).
Additionally, a genetic predisposition is likely as there is a higher incidence of apnea of prematurity in infants born to first-degree consanguineous parents compared with other infants (Tamim, Khogali, Beydoun, Melki, &
Yunis, 2003).
Apnea of prematurity generally resolves by 36–40 weeks’ PMA; however, the more premature the infant, the longer it lasts. In general, the risk of apnea of prematurity seems to resolve by 43–44 weeks’ PMA (Ramanathan et al., 2001). Although preterm infants make a disproportionate percent (18%) of sudden infant death syndrome (SIDS), there is no relationship between apnea of prematurity and SIDS (Committee on Fetus and Newborn, 2003).
Pathophysiology
Apnea of prematurity is due to the immaturity of the preterm infant’s brain and respiratory muscles (Darnall, Ariagno, & Kinney, 2006). Premature infants have an imbalance in the neural inputs that stimulate breathing and the inhibitory pathways that depress it. Developmental abnormalities in the regulation and production of neurotransmitters such as gaminobutyric acid (GABA), adenosine, serotonin, endorphins, and prostaglandin have been suggested as possible contributing causes to apnea of prematurity (Abu-Shaweesh & Martin, 2008).
Premature infants have blunted respiratory responses to hypoxia (decreased delivery of oxygen to tissues) and hypercapnia (elevated carbon dioxide levels); they do not appropriately increase their breathing efforts in response to either. The impaired response to carbon dioxide is more pronounced in infants with apnea of prematurity (Gerhardt & Bancalari, 1984). Infants, both term and preterm, develop apnea when their larynx is stimulated, which is known as the laryngeal chemoreflex. Preterm infants have decreased tone in their upper airway, which makes them more sus- ceptible to upper airway obstruction. Sleep mechanisms are immature and they have a decrease in their ability to arouse in response to respiratory problems, particularly in the prone position (Bhat et al., 2006).
Neonatal lung disease: Apnea of prematurity and bronchopulmonary dysplasia 87
Apnea of prematurity can be central, obstructive, or mixed. Central apnea is the complete cessation of breathing effort; the brain fails to send the appropriate signals to the respiratory muscles to breathe. Obstructive apnea occurs when the infant’s upper airway collapses and air cannot flow in or out of the infant’s mouth; however, the infant continues to try to breathe. Mixed apneas have components of both during an episode.
In response to the apnea, infants often become hypoxic and bradycardic.
Lung volumes, specifically functional residual capacity (FRC), are low, which predisposes them to hypoxemia when they develop apnea (Tourneux et al., 2008). Hypoxia itself can produce apnea in preterm infants, which may increase the severity and duration of the apneic episode. Bradycardia is also seen with apnea. The mechanism is not well understood. It may be directly produced by the stimulus that causes the apnea or may be due to enhanced sensitivity to vagal nerve stimulation. In addition, hypoxia itself can also cause bradycardia. Apneas are worse during active rather than quiet sleep.
Events that further depress an infant’s brain function, such as sepsis or intracranial bleeds, may increase the incidence and severity of apnea. For many years, it was believed that gastroesophageal reflux worsens apnea.
However, recent studies do not bear out the association (Di Fiore, Arko, Whitehouse, Kimball, & Martin, 2005). Prone position is associated with an increase in central apneas and a decrease in arousals (Bhat et al., 2006).
Signs and symptoms
Apnea presents with episodes of hypoxemia and bradycardia. It may also be associated with hypotension. Classically, the infant may turn blue, pale, limp, and mottled and makes little or no respiratory effort. Heart rate by cardiac monitoring decreases to less than 80 beats/min. Oxygen satura- tions by pulse oximetry decrease to less than 85%. Apnea of prematurity may be temporally associated with feeds. Infants may recover by them- selves or may require stimulation in order to terminate the episode.
Diagnosis
The diagnosis is made clinically when a lack of respiratory effort is observed along with bradycardia and hypoxemia. In the neonatal intensive care unit (NICU), cardiorespiratory monitoring will pick up bradycardia and hypox- emia. Blood gases are rarely used for diagnosis since cannulation of the artery or vein often causes enough stimulation to terminate the apnea.
Secondary causes of apnea should be ruled out such as sepsis and intra- cranial hemorrhage.
In cases where the diagnosis is more challenging, polysomnography (sleep study) may be used to better delineate the characteristics of the episodes. It can differentiate between central, obstructive, and mixed apneas. During polysomnography, many physiological parameters are
88 Nursing Care in Pediatric Respiratory Disease
monitored: electroencephalogram (EEG), electrocardiogram (ECG), respi- rations, oxygen saturation levels, carbon dioxide levels, muscle tone, and eye and extremity movements. It can determine the exact duration of an apneic episode and can assess the resultant physiological consequences such as bradycardia, hypoxemia, arousals, and hypercapnia. Monitoring with a pH probe, during the test, can also determine the presence and relationship of gastroesophageal reflux to apnea.
After discharge from the NICU, respiratory monitoring can detect per- sistent apnea. The most common type of “apnea monitor” is the transtho- racic electrical impedance. The apnea monitor has two parts: a belt or electrodes with sensory wires that a baby wears on the chest and a moni- toring unit with an alarm. The sensors measure the baby’s chest movement and breathing rate, while the monitor continuously records these rates.
These monitors are generally effective in identifying and alarming with central apneas; however, apneas are sometimes identified even though the infant is breathing (false positive), and true apneas are not detected because of background “noise,” such as cardiac beats (false negative).
Complications
Apnea of prematurity can prolong hospitalization of infants and may require more invasive treatment with positive pressure ventilation and medications. Repeated episodes of hypoxia and bradycardia might cause brain injury. Apnea of prematurity has been associated with impairment in neurological development; infants demonstrate lower scores on Bayley Scales of Infant Development and a higher incidence of cerebral palsy and blindness (Hunt et al., 2004; Janvier et al., 2004). Despite the fact that preterm birth is associated with a higher incidence of SIDS, apnea of pre- maturity does not seem to be an independent risk factor for SIDS.
Management
Mild episodes of apnea can improve without intervention. More significant episodes may require tactile stimulation—that is, stimulating the infant’s limbs, back, or body. Stimulation is a well-recognized treatment for apnea of prematurity. In the past, oscillatory or “bump beds” were used to stimu- late the infants. For severe episodes of apnea, the infant may require manual breaths and supplemental oxygen via bag–mask valve ventilation.
If the apnea persists, the infant may require support with intubation and positive pressure ventilation. Alternatively, administration of continuous positive airway pressure (CPAP), intermittent positive pressure ventila- tion, or high-flow gas via nasal cannula may be effective (Pantalitschka et al., 2009). Transfusions with packed red blood cells to treat anemia has been associated with a transient decrease in apneic episodes (Bell et al., 2005).
The mainstay of medical treatment is the use of methylxanthines, pri- marily caffeine (Bhatt-Mehta & Schumacher, 2003). Methylxanthines stim-
Neonatal lung disease: Apnea of prematurity and bronchopulmonary dysplasia 89
ulate the respiratory and central nervous systems of the preterm infant. In the past, theophylline was widely used. However, caffeine supplanted it as the drug of choice because it is as effective as theophylline but has a longer half-life and fewer side effects. Doxapram, a respiratory stimulant, has been investigated. It is not available in the United States and there is insufficient information about its effects and adverse reactions.
Caffeine is usually discontinued after a period without apnea and bra- dycardia or at the time when apnea begins to decrease in frequency at 34–36 weeks’ PMA. After discontinuing the medication, most NICUs require the infant to have a period of 3–7 days without apnea and brady- cardia before discharging the infant to home. However, in some infants, particularly those born less than 28-weeks gestation, the episodes persist longer which may delay discharge. In those cases, home apnea monitors may be used (Committee on Fetus and Newborn, 2003). Monitoring con- tinues until the infants are 43 weeks’ PMA or after the cessation of extreme episodes, whichever comes last. The monitors should be equipped with an event recorder, which keeps a record of the events. The information can be downloaded and sent to the primary care provider for review. Of note, home cardiorespiratory monitoring has never been proven to decrease the incidence of unexpected deaths in premature infants.
Nursing care of the child and family
The nursing care of the infant with apnea of prematurity must be system- atic and comprehensive. It also requires knowledge of the three different types of apneic episodes described earlier in this chapter—central, obstruc- tive, and mixed.
The first crucial component of care is that the nurse should be able to accurately identify periods of apnea so that the appropriate intervention can be initiated. A monitor (cardiac/apnea/pulse oximeter) should be instituted for all infants diagnosed with apnea of prematurity. The leads must be well placed (in a manner such that they visibly capture the infant’s respiratory pattern on the monitor) and the alarms set appropriately (Calhoun, 1996). The heart rate alarm should be based on the infant’s baseline heart rate. The respiratory alarm should notify the caregiver when the infant has been apneic for greater than 20 seconds. Typical settings include a low heart rate of 80–100 beats/min with a 20-second apnea delay (Theobald, Botwinski, Albanna, & McWilliam, 2000). Alarm limits should be designed to provide the nurse time to arrive to the bedside and assess the infant.
Assessment of an apneic episode includes color, respiratory rate and effort, oxygen saturation level, heart rate, and position (Theobald et al., 2000). A thorough assessment will help to determine if the apnea is central, obstructive, or mixed. If the infant is having central apnea, the apnea alarm will probably be the first to sound. Heart rate and oxygen saturation alarms may follow if the apneic episode is prolonged and leads to hypoxia and/
90 Nursing Care in Pediatric Respiratory Disease
or bradycardia. If the infant is experiencing obstructive apnea, the satura- tion or possibly the heart rate would alarm first as the infant continues to try to breathe. If unsuccessful, the infant will eventually become apneic. In this case, the apnea alarm is a late indicator that the infant is in trouble.
Common triggers for apnea include feeding, suctioning, temperature changes, and immunizations (Calhoun, 1996; Stokowski, 2005; Theobald et al., 2000). The primary intervention for an apneic episode is tactile stimu- lation, such as foot rubbing (Stokowski, 2005; Theobald et al., 2000). If the infant is not bradycardic or hypoxic, the nurse should observe the infant for a short period of time (approximately 15 seconds) before stimulating the infant to see if he/she will trigger his/her own respirations. If the infant does not spontaneously begin to breathe or if the heart rate or oxygen satu- ration level drop, the nurse must intervene. If tactile stimulation is insuf- ficient, a more vigorous stimulation, supplemental oxygen, or bag–mask ventilation should be instituted (Stokowski, 2005; Theobald et al., 2000).
With obstructive apnea, the infant may require suctioning or repositioning to open his/her airway. Preventive nursing interventions include main- taining a neutral temperature, proper positioning and avoidance of neck flexion, appropriate placement of the nasogastric tube if applicable, slow feedings, avoidance of deep suctioning, and providing periods of undis- turbed sleep (Stokowski, 2005; Theobald et al., 2000).
All apnea episodes must be reported and documented. Documentation of apneic episodes is a vital aspect of care. Documentation should include the date and time of the event, the duration of apnea, associated episodes of bradycardia, oxygen saturation level, any precipitating events, and intervention required (Calhoun, 1996).
Apnea of prematurity is also treated pharmacologically with the use of methylxanthines (Calhoun, 1996; Theobald et al., 2000). Therefore, the nurse must monitor the therapeutic and adverse effects of pharmacological therapy. Side effects of methylxanthines include tachycardia, tachypnea, glucose instability, jitteriness, restlessness, tremors, irritability, vomiting, and feeding intolerance (Theobald et al., 2000). Methylxanthines can lead to mild diuresis. Therefore, intake and output should be monitored closely, especially if the infant is on a diuretic (Calhoun, 1996; Gannon, 2000;
Theobald et al., 2000).
Theophylline and caffeine are two methylxanthines that have been used in the management of apnea of prematurity. Methylxanthines are thought to stimulate breathing efforts; however, their mechanism of action is not certain (Henderson-Smart & Steer, 2010). A recent review revealed that caffeine and theophylline have similar short-term effects on apnea and bradycardia; however, caffeine is associated with less toxicity, a higher therapeutic ratio, more reliable enteral abosorption, and a longer half-life (Henderson-Smart & Steer, 2010).
Caffeine can be given once a day. It provides stable, predictable plasma concentrations and a wide therapeutic range. Most institutions monitor caffeine levels every 1–2 weeks, while some do not feel monitoring is neces-
Neonatal lung disease: Apnea of prematurity and bronchopulmonary dysplasia 91
sary (Theobald et al., 2000). A therapeutic trough caffeine serum level is 5–25 µg/mL (Gannon, 2000). As previously mentioned, theophylline is not used often because caffeine has increased efficacy and a better safety profile. However, when it is used, it is dosed every 8–12 hours. Serum levels between 7 and 12 µg/mL are generally acceptable (Gannon, 2000).
Because theophylline toxicity can occur if levels are slightly higher than the acceptable range, serum levels are checked frequently (Gannon, 2000).
Theophylline can affect sleep/wake patterns and can cause gastric irrita- tion. Therefore, it should not be given in the afternoon and stools should be tested for occult blood (Calhoun, 1996; Gannon, 2000; Theobald et al., 2000).
When caring for the infant with apnea of prematurity, it is important to keep the parents informed and well educated. Parents should be updated on their infant’s status as well as on changes in therapy. Information regarding apnea of prematurity and its progression is usually welcomed by parents. Knowing that the apnea is likely related to the infant’s imma- turity and will improve over time can help decrease the parents’ level of anxiety. Other educational messages should include positioning, proper feeding techniques, sleep safety measures, avoidance of secondhand smoke, and avoidance of large crowds or exposure to sick contacts. If the infant is experiencing desaturations and/or bradycardia related to posi- tioning, parents should be instructed on the proper positioning that will maintain the infant’s airway. Parents should also be instructed to hold their infant semi-upright while feeding and to observe the infant’s sucking and breathing patterns during the feed. Premature infants may need to have the bottle removed from their mouth to allow them time to rest between long sucking bursts. At home, parents should also be instructed to feed their infants in an area that is well lit so that they can readily assess the infant’s color if an apneic episode occurs (Stokowski, 2005). Parents must be informed that the infant should be maintained in a supine position during sleep and they should avoid having the infant sleep with them in their bed.
Typically, infants are discharged once they are free from apneic episodes for 3–7 days. However, home monitoring can be arranged. The decision to discharge an infant with an apnea monitor is usually institution specific and provider related (Stokowski, 2005). If the infant is discharged home on a monitor, it is important that the parents be informed that the purpose of the monitor is not to prevent SIDS but to provide early recognition of an apneic episode (Stokowski, 2005).
BPD
Epidemiology
BPD is the most common chronic lung disease of infancy (CLDI). It was first described in 1967 by Northway et al. in premature infants who had
92 Nursing Care in Pediatric Respiratory Disease
been exposed to high levels of supplemental oxygen and prolonged mechanical ventilation (Northway, Rosan, & Porter, 1967). Very premature infants are at risk of neonatal RDS and often require support with supple- mental oxygen and positive pressure ventilation. BPD occurs primarily in infants who are delivered at a gestational age of less than 30 weeks with a birth weight of less than 1,500 g. BPD occurs in approximately 20% of infants less than 1,500 g (Fanaroff et al., 2007) and one-third of those less than 1,000 g (Walsh et al., 2006). Despite the introduction of antenatal cor- ticosteroids, postnatal surfactant replacement, and more gentle modes of positive pressure ventilation, the incidence of BPD has remained stable throughout the last two decades. Though these interventions have decreased the risk of BPD in older, preterm infants, the younger, more preterm infants are now surviving with an increased incidence of BPD.
The development of BPD has been associated with maternal preeclamp- sia (Hansen, Barnes, Folkman, & McElrath, 2010), chorioamnionitis (Watterberg, Demers, Scott, & Murphy, 1996), high fluid administration in the early newborn period (Van Marter, Leviton, Allred, Pagano, & Kuban, 1990), patent ductus ateriosus (Brown, 1979), adrenal insufficiency (Watterberg, Gerdes, Gifford, & Lin, 1999), neonatal infections, such as ureaplasma urealyticum (Colaizy, Morris, Lapidus, Sklar, & Pillers, 2007) and cytomegalovirus (Sawyer, Edwards, & Spector, 1987), vitamin A defi- ciency (Inder, Graham, Winterbourn, Austin, & Darlow, 1998), and intra- uterine growth restriction (Bose et al., 2009).
There may be a genetic predisposition to RDS and a subsequent devel- opment of BPD. Analysis of twin pairs demonstrates an increased associa- tion of BPD in identical versus fraternal twins (Lavoie, Pham, & Jang, 2008).
The development of BPD has been correlated with certain genetic poly- morphisms or variants (Kwinta et al., 2008; Levit et al., 2009). A family history of asthma has been associated with BPD; however, recent data are not supportive (Evans, Palta, Sadek, Weinstein, & Peters, 1998).
Pathophysiology
Preterm infants have immature lung development. They have a decreased number of branching airways and alveoli. They are deficient in surfactant, which is important for the stability of the alveoli. With insufficient surfac- tant, the alveoli collapse and develop areas of atelectasis, further impairing gas exchange. As a result, the infants develop respiratory distress and hypoxemia. Prior to the development of surfactant replacement therapy, chest radiographs typically showed a diffuse reticulogranular infiltrate with air bronchograms, and pathology revealed evidence of “hyaline mem- brane disease.”
BPD results from injury induced by the supplemental oxygen and posi- tive pressure ventilation that the preterm infant requires for survival. In addition, there is evidence that immature lungs of the extremely low birth