Respiratory Distress Syndrome

Respiratory distress syndrome (RDS), also known as hyaline membrane disease, is the end result of a relative surfactant deficiency that, when combined with the compliant chest wall of the neonate, promotes alveolar atelectasis and prevents newborns from developing a normal functional residual capacity (Figure 102-1). The most significant risk factor for RDS is prematurity because surfactant production begins between 24 and 28 weeks of gestation and does not become fully functional until at least 35 weeks. Other risk factors for the development of RDS include maternal diabetes; early-onset sepsis; and less commonly, congenital surfactant deficiency. Fifty percent of infants with birth weights between 500 and 1500 g develop some degree of respiratory distress; however, survival is greater than 90% with the use of exogenous surfactant and antenatal steroids.

Figure 102-1 Respiratory distress syndrome of the newborn.

Transient Tachypnea of the Newborn

Transient tachypnea of the newborn (TTN) is one of the most common respiratory disorders of newborns with an incidence of 5.7 per 1000 deliveries. TTN occurs as a result of delayed reabsorption and clearance of fetal alveolar fluid from the airways. Throughout gestation, epithelial cells in the lung secrete alveolar fluid. In the late gestational period, epithelial ion channels shift from active secretion of sodium and chloride to active reabsorption caused by high circulating levels of maternal epinephrine. At birth, inspired oxygen increases gene expression of the sodium transporter, which further facilitates fluid shifts from the airways to the interstitium and intravascular space. Passive fluid reabsorption is also postulated to play a role. However, the accumulation of fluid in the interstitium can decrease lung compliance and prevent the establishment of functional residual capacity.

Factors that increase the likelihood of TTN include nonreassuring fetal status, instrumentation at delivery, Apgar score less than 7 at 1 minute, male sex, in vitro fertilization, multiple gestation, and macrosomia. Relevant maternal characteristics include history of maternal asthma, maternal diabetes, and nulliparity. Cesarean section poses a theoretical risk because of the absence of a “squeeze” effect created by passage through the vagina, which may increase the passive absorption of alveolar fluid. The risk of TTN in the setting of cesarean section increases with absence of labor before delivery and with delivery before 39 weeks.

Meconium Aspiration Syndrome

Meconium aspiration syndrome (MAS) is defined as respiratory distress in a newborn in the setting of meconium-stained amniotic fluid, whose distress cannot be otherwise explained. Meconium is a combination of amniotic fluid, bile, water, intestinal epithelial cells, lanugo, and mucous, all of which are swallowed by the fetus. A fetus in distress is likely to pass meconium because the stress response results in a relaxation of the anal sphincter and subsequent release of meconium. Fetal distress, when prolonged, can provoke fetal gasping and increase the likelihood of aspiration. When aspirated into the airway, meconium contributes to respiratory distress by obstructing the airway, inactivating surfactant, and producing an inflammatory response that damages the respiratory epithelial barrier and predisposes the neonate to serious bacterial infection. The inflammatory response leads to vasoconstriction and persistent pulmonary hypertension in 20% of infants, with an increased risk in infants who experience chronic intrauterine hypoxemia. Meconium staining occurs in 10% to 20% of all deliveries and accounts for 2% of all perinatal mortality.

Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is defined as oxygen dependency in a premature infant continuing past 36 weeks corrected gestational age. An exaggerated inflammatory response occurs soon after birth in the incompletely developed lung, which is exacerbated by positive-pressure ventilation and prolonged mechanical ventilation, which can result in barotrauma and further lung damage over time. There are currently two descriptions of BPD in the literature. The first is seen in premature infants resuscitated as the field of neonatology initially expanded, with the majority of lung damage attributable to mechanical ventilation and its effects (barotrauma, endotracheal bacterial colonization, high inspired oxygen concentration). As mechanical ventilation of neonates has become more refined over time, histologic examination has revealed a changing pattern of lung damage, including fewer and larger alveoli with abnormal septation and an otherwise normal airway. This pattern is best conceptualized as an arrest in development with simplified architecture. As resuscitation techniques have permitted neonates of earlier gestational ages to survive, these changes are attributable not only to mechanical ventilation but also to the effects of sepsis and extreme prematurity. The role of a persistent patent ductus arteriosus continues to be the subject of considerable debate and research. The risk of a premature infant with RDS progressing to BPD decreases linearly with increasing gestational age. Antenatal steroid administration also decreases the risk of BPD.

Pneumothorax

Air leak syndromes, as the name implies, result from rupture of the alveolar sac with subsequent flow of air into the interstitial spaces of the lung, and they occur in the setting of a rapid change in intrathoracic pressure. In term infants, pneumothorax is the most common result of an air leak and occurs in 1% of all deliveries (Figure 102-2). Risk factors include positive-pressure ventilation with high peak inspiratory pressures (>20–25 mm Hg) and surfactant administration. Pneumothorax may occur spontaneously at birth even without application of positive-pressure ventilation.

Figure 102-2 Pneumothorax.

Anatomic Abnormalities

Congenital anomalies of the pulmonary system may or may not be prenatally diagnosed and include the following disorders: choanal atresia, a congenital blockage of the posterior nares; trachea-esophageal fistula; congenital diaphragmatic hernia (CDH), a patent pleuroperitoneal canal that allows the intestines to occupy the pleural space and results in pulmonary hypoplasia (Figure 102-3); congenital cystic adenomatous malformation (CCAM); bronchopulmonary sequestration, in which a segment of lung parenchyma is not supplied by the pulmonary blood supply and does not communicate with the bronchial tree (see Figure 102-3); bronchogenic cysts; congenital lobar emphysema, which results in air trapping in one lung segment; vascular rings and slings; and Pierre Robin sequence and other maxillofacial malformations. A full exploration of these disorders is beyond the scope of this chapter, but it is important to keep them in mind when faced with an infant with respiratory distress without risk factors for the more common disorders described above.

Figure 102-3 Anatomic abnormalities.

Initial Evaluation

Chest radiography is the best test to differentiate between RDS and TTN, the most common causes of respiratory distress in newborns. Whereas fluid in the interlobar fissure, with perihilar streaking, indicates TTN, a uniform reticulogranular pattern (“ground-glass appearance”) and peripheral air bronchograms suggest RDS (Figure 102-4). Chest radiography is also useful to evaluate for pneumonia, congenital heart disease, pneumothorax, and CDH. Radiographic findings of pneumothorax are air in the pleural cavity resulting in hyperlucency with absence of pulmonary markings in the affected area. A more subtle chest radiography finding suggestive of pneumothorax is a downward displacement of the diaphragm, which can be verified with a cross-table lateral chest radiograph as an anterior mediastinal collection of air.

Figure 102-4 Manifestations of hyaline membrane disease in the newborn.

Arterial blood gas analysis is useful to guide therapy in a variety of causes of respiratory failure. Elevated carbon dioxide levels indicate a need for increased respiratory support. Extremely low partial pressure of oxygen in the face of high inspired oxygen is a marker of severe pulmonary disease or intracardiac shunting of blood in the setting of congenital heart disease. Alkalosis in the setting of tachypnea may indicate a neurologic cause. A metabolic acidosis most commonly indicates significant systemic illness with inadequate delivery of oxygen and nutrients to end organs but can also suggest an inborn error of metabolism.

Other evaluation and management of respiratory distress should be pursued as the clinical history and examination indicate. Pulse oximetry, screening and treatment for sepsis, and blood sugar measurement are all appropriate first-line interventions. Neonates with an elevated respiratory rate should not feed by mouth because of increased risk of aspiration and may require intravenous fluids or nasogastric feeding. Echocardiography is warranted if the cardiac examination, persistent cyanosis, and vital signs suggest congenital heart disease.

Disease-Specific Management

Respiratory distress syndrome is a result of surfactant deficiency, and if distress or hypoxemia is severe, surfactant administration can significantly reduce distress and the need for invasive ventilation. The use of surfactant has also been noted to decrease the incidence of intraventricular hemorrhage in preterm infants.

The management of an infant with meconium-stained amniotic fluid occurs per the Neonatal Resuscitation Program guidelines. If vigorous, infants with meconium-stained amniotic fluid may be observed for signs of respiratory distress; suctioning in vigorous infants has not prevented MAS in large, prospective, randomized trials. If amniotic fluid is meconium stained and the newborn is not vigorous at delivery, immediate nasopharyngeal suctioning at the perineum is not indicated. Instead, endotracheal intubation for the purpose of suctioning meconium from the trachea before the onset of respiration is recommended to remove all gross particulate meconium from the airway. This prevents meconium from being further aspirated into the lungs and may prevent progression to MAS. Patients with MAS and persistent pulmonary hypertension may require a high level of respiratory support, including high-frequency oscillatory ventilation, inhaled nitric oxide, and endotracheal administration of surfactant. Extracorporeal membrane oxygenation (ECMO) may be indicated, and infants should be referred to an ECMO center for evaluation. Overall, despite an intensive hospital course, survival from MAS is approximately 90%.

Transient tachypnea of the newborn is made retrospectively as a diagnosis of exclusion. Care is supportive; prospective randomized, controlled trials have shown no benefit to using furosemide or inhaled racemic epinephrine treatments. TTN generally resolves within 72 hours; prolonged tachypnea (>60 rpm) or deteriorating clinical status should prompt further evaluation.

The degree of respiratory distress dictates the management of pneumothorax. Infants with mild distress may require little more than oxygen supplementation and close monitoring. Moderate to severe distress warrants emergent decompression and chest tube placement until the infant is clinically stable. Hemodynamic instability indicates a tension pneumothorax that should be immediately decompressed.