Background

Transient tachypnea of the newborn (TTN), often called type II RDS, is probably the most common respiratory disorder of newborns. The cause of TTN is unclear, but it is most likely related to delayed clearance of fetal lung liquid.15–29 During most births, approximately two-thirds of this fluid is expelled by thoracic squeeze in the birth canal; the rest is reabsorbed through the lymphatic vessels during initial breathing. These mechanisms are impaired in infants born by cesarean section or infants with incomplete development of the lymphatic vessels (preterm or small-for-gestational-age infants). The residual lung fluid causes an increase in airway resistance and an overall decrease in lung compliance. Because compliance is low, the infant must generate more negative pleural pressure to breathe. This process can result in hyperinflation of some areas and air trapping in others. Most infants with TTN are born at term without any specific predisposing factors in common. Mothers of neonates who have TTN tend to have longer labor intervals and a higher incidence of failure to progress in labor, which leads to cesarean delivery. In many cases, however, maternal history and labor and delivery are normal.

Clinical Manifestations

During the first few hours of life, infants with TTN breathe rapidly. Alveolar ventilation, as measured by arterial pH andPaCO₂, usually is normal. The chest radiographic findings, which may initially be indistinguishable from pneumonia, are hyperinflation, which is secondary to air trapping, and perihilar streaking. The perihilar streaking probably represents lymphatic engorgement. Pleural effusions may be evident in the costophrenic angles and interlobar fissures.

Treatment

Infants with TTN usually respond readily to a low FiO₂ by infant O₂ hood or nasal cannula. Infants requiring a higher FiO₂ may benefit from CPAP. Because the retention of lung fluid may be gravity-dependent, frequent changes in the infant’s position may help speed lung fluid clearance. Because TTN and neonatal pneumonia have similar clinical signs, intravenous administration of antibiotics should be considered for at least 3 days after appropriate culture samples are obtained. Mechanical ventilation is rarely needed, and when it is, this probably indicates a complication. Clearing of the lungs evident on a chest radiograph and with clinical improvement usually occurs within 24 to 48 hours. A few infants with TTN eventually have persistent pulmonary hypertension.

Background

Meconium aspiration syndrome (MAS) is a disease of term and near-term infants. It involves aspiration of meconium into the central airways of the lung. It usually is associated with perinatal depression and asphyxia.

Pathophysiology

Amniotic fluid consists mainly of fetal lung fluid, fetal urine, and transudate from the uterine wall. Meconium, the contents of the fetal intestine, occasionally is expelled from the fetus into the surrounding amniotic fluid. Meconium consists of mucopolysaccharides, cholesterol, bile acids and salts, intestinal enzymes, and other substances. Meconium normally is not passed until after delivery.³⁰ Infants who have marked perinatal depression or perinatal asphyxia may pass meconium in utero. The pathophysiologic control mechanisms for the passage of meconium in utero are not completely understood. It is widely accepted that infants can have meconium aspiration in utero. Amniotic fluid stained with meconium is found in approximately 12% of all births.³⁰ Meconium-stained amniotic fluid is rare among infants of less than 37 weeks’ gestational age. The clinical syndrome develops in 2 of every 1000 infants. Of infants with inhaled meconium, 95% clear their lungs spontaneously.³⁰Amniotic fluid infusion into the uterus before the delivery of infants with meconium-stained fluid has been shown to improve neonatal outcomes.^31,32

For many years, the aspirated meconium itself was considered the primary cause of MAS. More recent evidence suggests that the real causative agent is fetal asphyxia that precedes aspiration.²³ Fetal asphyxia causes pulmonary vasospasm and hyperreactivity of the vasculature, which lead to persistent pulmonary hypertension.

MAS involves three primary problems: pulmonary obstruction, lung tissue damage, and pulmonary hypertension.³³ Obstruction occurs because of plugging of the airways with particulate meconium. This obstruction often is of the ball-valve type, which allows gas entry but prevents gas exit. Ball-valve obstruction causes air trapping and can lead to volutrauma (Figure 31-3). The lung tissue injury caused by MAS is chemical pneumonitis. Additionally, there are various chemical effects, inflammatory responses, cytokine and chemokine activations, complement activation, and phospholipase A₂ activation.^33–37 Persistent pulmonary hypertension with intracardiac and extracardiac right-to-left shunting frequently complicates MAS.³⁰

Clinical Manifestations

Before birth, thick meconium, fetal tachycardia, and absent fetal cardiac accelerations during labor are evidence that the fetus is at high risk of MAS.³⁸ After delivery, if the infant has a low umbilical artery pH, an Apgar score less than 5, and meconium aspirated from the trachea, intensive care and close observation for MAS are warranted. Infants with MAS typically have gasping respirations, tachypnea, grunting, and retractions. The chest radiograph usually shows irregular pulmonary densities, which represent areas of atelectasis, and hyperlucent areas, which represent hyperinflation secondary to air trapping (Figure 31-4). Arterial blood gases typically show hypoxemia with mixed respiratory and metabolic acidosis. In the most severe cases, there is right-to-left shunting and persistent pulmonary hypertension.³⁰

Treatment

It is no longer recommended that vigorous infants with meconium-stained fluid be intubated and suctioned.31,39–41 However, it is important that an endotracheal tube be inserted immediately in severely depressed infants with thick meconium, and suction should be applied directly to the endotracheal tube.⁴⁰ The endotracheal tube is removed and inspected for meconium. If meconium is present, the procedure is repeated with a new endotracheal tube until no further meconium is aspirated or until two to four aspirations have been performed. The endotracheal tube should be left in place, and mechanical ventilation should be started. For prevention of hypoxemia, a flow of warmed 100% O₂ should be blown across the infant’s face during the aspiration efforts. No evidence suggests an improved outcome because of endotracheal suctioning in the care of infants who have meconium and are vigorous and would not otherwise require intubation.^42,43 There is evidence that tracheal lavage with dilute surfactant improves the clinical course and outcome of infants with MAS.^44–46

If the infant’s condition worsens, CPAP or mechanical ventilation may be indicated. CPAP is indicated if the primary problem is hypoxemia. By distending the small airways, CPAP can sometimes overcome the ball-valve obstruction and improve both oxygenation and ventilation. If respiratory acidosis is severe or clinical assessment indicates excessive work in breathing, mechanical ventilation should be started. Figure 31-3 shows the ball-valve effect. At rest, the airway lumen is partially obstructed. With inspiration, negative intrathoracic pressure opens the airway and relieves the obstruction. Gas enters and expands the alveoli. With expiration, intrathoracic pressure changes to a positive force, which narrows the airway and causes total occlusion. Gas cannot be expelled and is trapped within the alveoli. It is difficult to provide ventilation to infants with severe MAS. These infants often retain CO₂ and need increased ventilator support. Because of high airways resistance, the lungs have a long time constant. High ventilator rates and pressures increase the risk of air trapping and volutrauma.

Evidence suggests that both HFV and synchronous intermittent mechanical ventilation decrease the risk of air leak.⁴⁷ Various studies have shown improvement in MAS with the use of HFV and surfactant.⁴⁸ Nitric oxide has become a major adjunct in the management of persistent pulmonary hypertension.⁴⁹ Corticosteroids have not yet been shown to improve outcomes for infants with MAS.⁵⁰ High mean airway pressures may worsen pulmonary hypertension and aggravate right-to-left cardiac shunting.³⁸

Background

Infants, especially preterm infants, with severe respiratory failure in the first few weeks of life may develop a chronic pulmonary condition called bronchopulmonary dysplasia (BPD). BPD is a complex disease that is poorly defined.51–54 Historical definitions have included radiographic patterns and the requirement for supplemental O₂ at fixed time points in the infant’s life. Immaturity, genetics, malnutrition, O₂ toxicity, and mechanical ventilation all have been implicated in the origin of BPD.^51,55–62

Pathophysiology

The development of BPD is complex and involves many pathways. The initiating factors are related to atelectrauma (lung collapse) and volutrauma (large tidal volume [V_T]). Factors such as hyperoxia and hypoxia, mechanical forces, vascular maldevelopment, inflammation, nutrition, and genetics contribute to the abnormal development of the lung and lead to BPD.56,59,63–67 Atelectrauma is a term coined to describe loss of alveolar volume that is both a consequence and a cause of lung injury. Volutrauma is the term used to describe local overinflation (and stretch) of airways and alveoli. Atelectrauma leads to derecuitment (e.g., areas of alveolar collapse) of the lung. Volutrauma leads to damage to airways, pulmonary capillary endothelium, alveolar and airway epithelium, and basement membranes. The combination of atelectrauma and volutrauma synergistically increases lung injury.

Both atelectrauma and volutrauma cause a need for increased supplemental O₂ concentrations. This use of supplemental O₂ leads to overproduction of superoxide, hydrogen peroxide, and perhydroxyl radicals. Preterm infants are particularly susceptible to O₂ radicals because the antioxidant systems develop in the last trimester of pregnancy. Prolonged hyperoxia begins a sequence of lung injury that leads to inflammation, diffuse alveolar damage, pulmonary dysfunction, and death.

The response of the lungs to the combination of trauma and O₂ toxicity is the production and release of soluble mediators. These mediators probably are released from granulocytes residing in the lung. The release of these mediators can injure the alveolar-capillary barrier and induce an inflammatory response.⁶² A “new” BPD is being described that shows decreased alveolarization rather than the prominent airway damage of the “old” BPD. This change in the pathologic characteristics of BPD is thought to be related to improvements in ventilator management, the use of surfactant, and processes that interrupt alveolar development (e.g., postnatal steroid therapy).^54,68–70 Some authors speculate that the “new” BPD and “old” BPD are the same disease. The difference is that clinicians are better at performing mechanical ventilation in infants and do less damage to the airway compared with 20 years ago.⁷¹

Clinical Manifestations

BPD has various clinical manifestations. Some very immature infants may start with little or no O₂ requirement and little or no mechanical ventilation requirement. Progressive respiratory distress develops at approximately 2 to 3 weeks of life, and then the infant needs O₂ and mechanical ventilation. Other immature infants may begin with pneumonia or sepsis and need very high levels of O₂ and mechanical ventilation. In either of these scenarios, progressive vascular leakage and areas of atelectasis and emphysema develop in the lungs, and progressive pulmonary damage occurs. The chest radiograph in severe disease shows areas of atelectasis, emphysema, and fibrosis diffusely intermixed throughout the lung (Figure 31-5).^67,72 Arterial blood gas measurements reveal varying degrees of hypoxemia and hypercapnia secondary to airway obstruction, air trapping, pulmonary fibrosis, and atelectasis. There is a marked increase in airway resistance with an overall decrease in lung compliance.

Treatment

The best management of BPD is prevention. Prevention of atelectrauma and volutrauma begins in the delivery room. Establishment of an optimal FRC without overstretching the lung requires careful attention to detail in providing end-tidal pressure and avoiding large V_T. Surfactant should be delivered early in the course of treatment.

Treatment of infants with BPD involves steps to minimize additional lung damage and prevent pulmonary hypertension and cor pulmonale. Infants with severe disease may be dependent on supplemental O₂ or mechanical ventilation for months and have symptoms of airway obstruction for years. Therapy usually is supportive throughout the course of the disease. An infant with BPD is given respiratory support as needed. Supplemental O₂ can help decrease the pulmonary hypertension that is common with BPD.

Multiple pharmacologic treatments have been advocated for infants with BPD.⁷³ Diuretics are given as needed to decrease pulmonary edema; antibiotics are given to manage existing pulmonary infection.⁷⁴ Chest physical therapy may help mobilize secretions and prevent further atelectasis. Bronchodilator therapy may be useful in decreasing airway resistance.⁷⁵ Steroid therapy with dexamethasone can produce substantial short-term improvement in lung function, often allowing rapid weaning from ventilatory support. However, steroid therapy has little effect on long-term outcome such as mortality and duration of O₂ therapy.^76,77 Steroid therapy also has been implicated in decreased alveolarization and increased developmental delay.⁷⁸ Although steroids are still given in clinical practice, they should be used cautiously and only after the risks have been thoroughly explained to the parents.

Background

Apnea of prematurity is a common, controllable disorder among premature infants. It usually resolves over time.79–84 Premature infants frequently have periodic respiration, which comprises sequential short apneic episodes of 5 to 10 seconds followed by 10 to 15 seconds of rapid respiration. Apneic spells are abnormal if (1) they last longer than 15 seconds; or (2) they are associated with cyanosis, pallor, hypotonia, or bradycardia.

If no effort to breathe occurs during a spell, the apnea is called central apnea. If breathing efforts occur, but obstruction prevents airflow, the apnea is termed obstructive. Mixed apnea is a combination of the central and obstructive types that starts as obstructive apnea and then develops into central apnea.79–83,85

Etiology

Premature infants have immature control of respiratory drive in response to oxygen and carbon dioxide. In mature animals, an increase in alveolar PaCO₂ elicits an increase in V_T and respiratory rate. A decrease in FiO₂ below room air also triggers an increase in V_T. Conversely, in premature animals, an increase in PaCO₂ temporarily increases V_T but does not increase respiratory rate. A decrease in FiO₂ below room air decreases V_T and respiratory rate. This effect can lead to apnea in a premature infant. Several factors in addition to prematurity can cause apnea in infants. Table 31-2 summarizes the potential causes, associated signs, and diagnostic indicators.⁸⁶

Treatment

Infants with apnea need continuous monitoring of heart and respiratory rates. Continuous noninvasive monitoring of oxygenation by transcutaneous electrode or pulse oximetry is recommended. Most apneic incidents can be quickly terminated with gentle mechanical stimulation, such as picking the infant up, flicking the sole of the foot, or rubbing the skin.79,81,82,85,87 If the cause of apnea is not prematurity, treatment must be directed at resolving the underlying condition. Table 31-3 outlines current treatment strategies for infants with apnea.⁸⁶ Apnea secondary to prematurity responds well to methylxanthines, especially theophylline and caffeine.^82,85,87 These agents stimulate the central nervous system and increase the infant’s responsiveness to CO₂. For infants with apnea that is refractory to treatment with theophylline, doxapram can be used.^88–90 However, doxapram is delivered by continuous infusion and has multiple toxicities.

CPAP can also be used to manage infant apnea.⁹¹ Although the mechanism of action is not established, CPAP probably increases FRC and improves arterial partial pressure of oxygen (PaO₂) and PaCO₂. CPAP may also stimulate vagal receptors in the lung, increasing the output of the brainstem respiratory centers. Severe or recurrent apnea that is unresponsive to these interventions may necessitate mechanical ventilatory support.

As the respiratory control mechanisms mature, apnea of prematurity normally resolves without intervention. Apneic spells begin to disappear by week 37 to 44 of postmenstrual age with no apparent long-term effects. Infants who have apnea of prematurity are not at higher risk of sudden infant death syndrome (SIDS) than other infants.

Apnea monitoring can allow infants who are otherwise ready for discharge but still having occasional episodes of apnea to go home.79,81,85,92–95 However, the presence of a home apnea monitor is a significant inconvenience to the family. Home monitors lack the sophisticated filtering systems of hospital monitors, and they have very frequent false alarms.

Background

Persistent pulmonary hypertension of the newborn (PPHN) is a complex syndrome with many causes.⁹⁶ The common denominator in PPHN is a return to fetal circulatory pathways, usually because of elevated PVR. This condition results in further right-to-left shunting, severe hypoxemia, and metabolic and respiratory acidosis.

Pathophysiology

In the uterus, the fetus does not use the lungs as a gas exchange organ. PVR is high, and systemic vascular resistance (SVR) is low. This condition produces a PVR/SVR ratio greater than 1. A fetus has two anatomic shunts that are not present in older infants, children, or adults: foramen ovale and ductus arteriosus. With a PVR/SVR ratio greater than 1 and the anatomic shunts, blood flow bypasses the lung either at the atrial level (foramen ovale) or at the pulmonary artery (ductus arteriosus). Intrauterine total pulmonary blood flow and systemic arterial O₂ saturation are low.

In the transition to extrauterine life, PVR decreases owing to gas filling of the lung and increasing PaO₂ in the pulmonary venous circulation. SVR increases with the removal of the placenta from the circulation, and this makes the PVR/SVR ratio less than 1. If PVR does not decrease to allow the PVR/SVR ratio to become less than 1, the infant has PPHN.

There are three fundamental types of PPHN: vascular spasm, increased muscle wall thickness, and decreased cross-sectional area of pulmonary vessels.⁹⁷ Vascular spasm is an acute event that can be triggered by many different conditions, including hypoxemia, hypoglycemia, hypotension, and pain. Increased muscle wall thickness is a chronic condition that develops in utero in response to several different etiologic factors, including chronic fetal hypoxia, increased pulmonary blood flow (e.g., intrauterine closure of the ductus arteriosus), and pulmonary venous obstruction (e.g., total anomalous pulmonary venous return with obstructed below-diaphragm return). Decreased cross-sectional area is related to hypoplasia of the lungs and occurs with congenital diaphragmatic hernia, Potter sequence (absent kidneys), and oligohydramnios syndromes (decreased amniotic fluid).

Clinical Manifestations

PPHN should be suspected when an infant has rapidly changing O₂ saturation without changes in FiO₂ or has hypoxemia out of proportion to the lung disease detected with chest radiography or PaCO₂ measurement. In infants with a significant shunt through the ductus arteriosus, there usually is a substantial gradient (>5%) between preductal and postductal O₂ saturation. This gradient can be found easily if two pulse oximeters are placed on the infant, one on the right arm and the other on either leg.

Treatment

Initial therapy for PPHN is removal of the underlying cause, such as administration of O₂ for hypoxemia, surfactant for RDS, glucose for hypoglycemia, and inotropic agents for low cardiac output and systemic hypotension. If correction of the underlying problem does not correct hypoxemia, the infant needs intubation and mechanical ventilation. Because pain and anxiety may contribute to PPHN, the infant may need sedation and, frequently, paralysis. If these measures do not improve oxygenation, the next step is HFV. This mode of ventilation allows a higher FRC without a large V_T. Inhaled nitric oxide is considered the next intervention.98–100 If all of these modalities fail to improve oxygenation, the infant may be a candidate for extracorporeal membrane oxygenation (ECMO).^99,101–103 Even with all of these therapeutic modalities, PPHN remains a complex disease with high morbidity.

Airway Diseases

Airway abnormalities have three fundamental mechanisms: internal obstruction, external obstruction, and disruption. Internal obstruction includes common problems, such as laryngomalacia, that cause obstructive apnea. Less common problems caused by internal obstruction are tracheomalacia, laryngeal webs, tracheal stenosis, and hemangiomas. All of these diseases usually manifest as a combination of inspiratory stridor, gas trapping, expiratory wheezing, and accessory respiratory muscle activity.

External compression can be caused by hemangiomas, neck or thoracic masses, and vascular rings. These lesions are far less common than diseases caused by internal obstruction, but they are not rare. The symptoms are similar to symptoms of internal obstruction. Neck masses usually are obvious at visual inspection. Intrathoracic masses and vascular rings must be suspected on the basis of the clinical manifestations: noise during the respiratory cycle that worsens with exertion. The infant may have difficulty with swallowing.

Airway disruptions usually are related to tracheoesophageal fistula (TEF) in a newborn. This malformation usually is associated with esophageal atresia. There are five types of TEF: esophageal atresia with a proximal fistula, esophageal atresia with a distal fistula, esophageal atresia with both a proximal and a distal fistula, esophageal atresia without either fistula, and an intact esophagus with a so-called H fistula.¹⁰⁴ The most common of these malformations is esophageal atresia with a distal fistula, which accounts for 85% to 90% of all TEFs. The least common is the H fistula. All of these malformations manifest as difficulty swallowing, bubbling and frothing at the mouth, and choking, in particular, during attempts at feeding. These anomalies can occur in isolation or as part of an association of defects. The most common is the VATER or VACTERL association of vertebral anomalies, imperforate anus, tracheoesophageal fistula, and renal or radial anomalies. In VACTERL, cardiac anomalies are added, and renal and limb anomalies replace renal or radial anomalies in the acronym. These associated anomalies must be sought in any infant with TEF. TEF is managed with surgical ligation of the fistula and reconnection of the interrupted esophagus.¹⁰⁵ Most infants with TEF have a good outcome; however, some infants have severe malformations that can cause chronic problems. Infants with TEF usually need only supportive respiratory care. They usually do not have lung disease. However, some infants need HFV because the air leak through the fistula can become larger than the airflow to the alveoli.

Lung Malformations

There is a broad spectrum of rare lung malformations that occur in the newborn period.106–108 These lesions are thought to be part of a continual spectrum of diseases that originate as defects in lung segmentation. The most common is congenital pulmonary adenomatoid malformation (CPAM); this was previously known as cystic adenomatoid malformation of the lung. CPAM is classified into five types on the basis of the type and size of the cyst.^109,110 The disease may affect entire lobes of the lung. The affected parts of the lung do not exchange gas and can become infected. The usual treatment is surgical removal of the affected lobe. There is also the potential for malignant transformation.

Some affected fetuses can develop hydrops in utero. Most infants with CPAM have symptoms of lung volume loss. As the mass expands, the normal surrounding lung is compressed. Some CPAMs resolve spontaneously. A few infants have severe cardiorespiratory compromise and need respiratory support and emergency surgery. However, better results are seen when surgery can be performed electively.

Other, less common lung malformations include pulmonary sequestration and lobar emphysema. Both of these diseases involve maldevelopment of lobes of the lung. Sequestration is a primitive, frequently cystic, lung lobe that is not in communication with the tracheobronchial tree and frequently receives no pulmonary vascular blood flow.

Lobar emphysema is an airway malformation that causes gas trapping in a lobe of the lung. These malformations manifest as space-occupying masses within the thorax. They usually are managed with surgical resection.

Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia is a severe disease that usually manifests in newborns as severe respiratory distress. The pathophysiologic mechanism is a complex combination of lung hypoplasia, including decreased alveolar count and decreased pulmonary vasculature; pulmonary hypertension; and unusual anatomy of the inferior vena cava.¹¹¹ This disorder varies between asymptomatic (rare) and severe life-threatening disease (frequent). There are two types of hernia: Bochdalek hernia (lateral and posterior defect, usually on the left) and Morgagni hernia (medial and anterior, may be on either side). Hernias that occur in the right hemidiaphragm may be less severe because the liver can block the defect and decrease the volume of abdominal contents that can enter the thorax.¹¹²

Some authors speculate that the diaphragmatic hernia complex is a developmental field defect and not just a simple cascade of events related to a hole in the diaphragm. This theory is partly based on long-term outcomes of survivors with diaphragmatic hernias. These survivors frequently have severe scoliosis in the direction of the diaphragm defect. They also frequently have severe esophageal reflux disease.

Most cases of congenital diaphragmatic hernia can be diagnosed in utero with ultrasonography. Physical examination may yield the following findings: scaphoid abdomen (because the abdominal contents are in the thorax), decreased breath sounds, displaced heart sounds (because the heart is pushed away from the hernia), and severe cyanosis (from lung hypoplasia and pulmonary hypertension). The diagnosis is established with chest radiography.

The general treatment of infants with congenital diaphragmatic hernia involves neonatologists and pediatric surgeons. Initial treatment is insertion of an endotracheal tube, paralysis, and mechanical ventilation. A large sump tube is placed in the stomach and connected to continuous suction. These therapies allow adequate ventilation and oxygenation and prevent gas insufflation of the intestine. Most centers delay surgical repair for several days to allow the natural decrease in PVR. On day 7 to 10 of life, a surgeon closes the defect. This scenario occurs only for infants with easily correctable pulmonary hypertension. Infants with severe pulmonary hypertension may need HFV and ECMO. At some centers, the diaphragm is repaired during ECMO. Most centers try to wean the infant from ECMO and then perform the repair. Despite all these advanced therapies, the mortality for this disease is high.¹¹³ Survival depends on many complex variables (e.g., liver herniation into the thorax, fetal head-to-lung ratio, initial PaO₂ and PaCO₂).^113,114

Abdominal Wall Abnormalities

Because all newborns are primarily abdominal breathers, the abdominal wall is an intrinsic part of the respiratory system. Large defects in the abdominal wall can cause severe respiratory compromise.¹¹⁵ One of the most common of these defects is omphalocele. An omphalocele is an abdominal wall defect that involves the insertion of the umbilical cord. The umbilical cord goes into the omphalocele. The bowel of an infant with an omphalocele is usually covered by a membrane that looks like the surface of the umbilical cord. Occasionally, the omphalocele membrane ruptures and exposes the bowel of the infant. Omphaloceles must be distinguished from gastroschisis. Gastroschisis is an abdominal wall defect that is completely separate from the insertion of the umbilical cord. The bowel of an infant with a gastroschisis is not covered by a membrane. Usually only large omphaloceles cause respiratory distress. When they are greater than 10 cm in diameter, these defects can cause severe respiratory distress and frequently necessitate prolonged mechanical ventilation.

Neuromuscular Control

Many diseases of poor neuromuscular control affect newborns,116–119 including spinal muscular atrophy, congenital myasthenia gravis, and myotonic dystrophy. These diseases frequently necessitate respiratory support in the newborn and pediatric periods. The morbidity and mortality of these diseases are extremely variable. New technologies may allow noninvasive respiratory support of some patients.¹²⁰ Some diseases can be quite severe in the newborn period and be relieved with age. It is important to make an accurate diagnosis to be able to estimate prognosis and to provide genetic counseling. Many of these diseases are inherited with known inheritance patterns.

Cyanotic Heart Diseases

The two most common cyanotic heart diseases are tetralogy of Fallot and transposition of the great arteries.

Acyanotic Heart Diseases

Some of the most common and most severe congenital heart diseases are acyanotic. Ventricular septal defect is probably the most common congenital heart disease. Hypoplastic left heart syndrome is one of the most severe congenital heart diseases.

Left Ventricular Outflow Obstructions

Hypoplastic left heart syndrome (Figure 31-7), interrupted aortic arch, and coarctation of the aorta have in common obstruction of left ventricular outflow.^130–132 They all manifest in the newborn period with symptoms of acute heart failure. Systemic blood flow depends on patency of the ductus arteriosus. When the ductus spontaneously closes (usually at 5 to 7 days of age), severe congestive heart failure develops. The symptoms range from moderate respiratory distress to complete cardiovascular collapse. Initial treatment is intravenous administration of prostaglandin E₁. Most infants with these defects need support with mechanical ventilation. These infants do not have lung disease. The pressures and rates used should be set appropriately.

There are standard surgical repairs for both interrupted aortic arch and coarctation of the aorta. Hypoplastic left heart syndrome has several accepted treatments, including a palliative surgical procedure (Norwood) and transplantation.130–132 Neither the Norwood procedure nor transplantation is ideal, and each option has significant associated problems. The decision must be made in consultation with the family.

Etiology

The cause of SIDS is unknown. Apnea of prematurity is not a predisposing factor, and there is no evidence that immaturity of the respiratory centers is a cause. Although infants in families in which two or more SIDS deaths have occurred are at slightly higher risk, there is no evidence of a genetic link. The best knowledge of SIDS comes from population or epidemiologic studies and is summarized in Box 31-2. An infant who dies of SIDS typically is a preterm African-American boy born to a poor mother younger than 20 years who received inadequate prenatal care. Infants 1 to 3 months old are most susceptible, and death is most likely to occur at night during the winter. The risk of SIDS also is high among infants who previously experienced an apparent life-threatening event. Such an event occurs when an infant becomes apneic, cyanotic, or limp enough to frighten the parent or caregiver. The prone sleeping position has been strongly associated with increased risk of SIDS. It is difficult to differentiate death of SIDS from death of intentional suffocation. The possibility of intentional suffocation must be investigated but with great sensitivity.¹⁴¹

Prevention

Because of the unknown causation and unexpected occurrence, there is no therapy for SIDS. Prevention is the goal. Successful prevention requires that infants at high risk be identified through a history of risk factors and documented monitoring or event recording. After identification that an infant is at risk, the family is trained in apnea monitoring and cardiopulmonary resuscitation (CPR). The AAP recommends placing infants in either the supine or the side-lying position for the first 6 months of life and reducing soft objects in the infant’s sleeping environment.92,140–142 To define the need and appropriate approach for home monitoring of infants, the AAP has developed a policy statement on infantile apnea and home monitoring.⁹² The AAP recommendations for the need for and use of home monitoring are summarized in Box 31-3.

Clinical Manifestations

The clinical manifestations of bronchiolitis are inflammation and obstruction of the small bronchi and bronchioles. Bronchiolitis commonly occurs soon after a viral upper respiratory infection. The infant may have a slight fever with an intermittent cough. After a few days, signs of respiratory distress develop, in particular, dyspnea and tachypnea. Progressive inflammation and narrowing of the airways cause inspiratory and expiratory wheezing and increase airway resistance. A chest radiograph shows signs of hyperinflation with areas of consolidation. The diagnosis of RSV infection can be established by immunofluorescent assay the same day and assists in the implementation of a treatment plan.

Clinical Manifestations

Symptoms become evident after 2 or 3 days of nasal congestion, fever, and coughing. A child typically has slow, progressive inspiratory and expiratory stridor and a barking cough. As the disease progresses, dyspnea, cyanosis, exhaustion, and agitation occur. A radiograph of the upper airway is helpful in confirming the diagnosis and ruling out epiglottitis but is usually not needed in most cases of croup.⁸⁴ Classic croup is seen on an anteroposterior radiograph as characteristic subglottic narrowing of the trachea, called the steeple sign (Figure 31-8).

Treatment

The evaluation and treatment of a child with croup must focus on the degree of respiratory distress and associated clinical findings. If stridor is mild or occurs only on exertion and cyanosis is not present, hospitalization is generally not required, and the child is treated at home. If there is stridor at rest (accompanied by harsh breath sounds, suprasternal retractions, and cyanosis with breathing of room air), hospitalization is indicated. The traditional treatment of a child with mild to moderate croup has involved cool mist therapy with or without supplemental O₂. However, there is no evidence that this practice is beneficial.¹⁶⁵ Corticosteroids and epinephrine have been shown to have the greatest benefit for decreasing the length and severity of respiratory symptoms associated with viral croup.^166,167 The addition of budesonide has been shown to reduce the severity of symptoms in mild to moderate cases of croup.^166,167 Progressive worsening of the clinical signs despite treatment indicates the need for intubation and mechanical ventilation. Heliox has been used for infants and children with severe disease. However, there is insufficient evidence to show whether this is beneficial.¹⁶⁸

Clinical Manifestations

A child with epiglottitis usually has a high fever, sore throat, stridor, and labored breathing.170–172 The patient does not have a croupy bark but instead has a muffled voice. Older children may report a sore throat and difficulty swallowing. Difficulty swallowing may cause drooling. Lateral radiographs of the neck (Figure 31-9) show the epiglottis is markedly thickened and flattened (thumb sign) and the aryepiglottic folds are swollen; the vallecula may not be visualized. Visual examination of the upper airway is dangerous in these children and always should be performed in a controlled setting by personnel expert in emergency intubation. Inadvertent traction of the tongue can cause further and immediate swelling of the epiglottis and abrupt and total upper airway obstruction. Children with suspected epiglottitis should be accompanied by personnel expert in emergency intubation during any transport for diagnostic procedures.

Treatment

Children with epiglottitis need elective intubation under general anesthesia in the operating room. Tracheostomy may be needed if the patient’s condition warrants it; however, this procedure is rarely used. There should be no attempt to lie the child down or attempts to intubate until the child is sedated. Premature attempts at intubation can precipitate acute airway obstruction and respiratory arrest. After an airway is secured, a sample for bacterial culture should be obtained, and antibiotic therapy should be started. Corticosteroids may decrease the swelling.¹⁷⁰ Children with an endotracheal tube should be sedated and restrained to prevent inadvertent extubation. Extubation should not be attempted until an upper airway leak is readily detected.

Clinical Manifestations

Patients with CF experience abnormalities in nearly all organs with exocrine function. The most severely affected organs are the sweat glands, pancreas, and lungs. Normal sweat is produced as a saline solution that has much of the salt removed on its way to the surface of the skin. Sweat glands of patients with CF are unable to remove salt from sweat properly.¹⁷⁶ As a result, the skin of patients with CF develops a salty taste, and they are prone to dehydration during hot weather.¹⁷⁷ The sweat chloride test used for diagnosis of the disease is based on the high salt concentration in the sweat of patients with CF.¹⁷⁸ Most patients with CF also have exocrine pancreatic insufficiency, which usually starts in infancy. Exocrine pancreatic insufficiency dramatically reduces the number of digestive enzymes, and patients lacking digestive enzymes do not break down large proteins, carbohydrates, and fats for absorption, causing malnutrition and diarrhea. Digestion of fats is particularly compromised in patients with CF. These patients often have deficiencies of the fat-soluble vitamins A, D, E, and K and have large amounts of undigested fat in the stool (steatorrhea).

Complications of lung disease are the leading cause of death in patients with CF. Patients have recurring pulmonary infections, often beginning during the first few years of life. The organisms associated with these infections frequently include S. aureus, H. influenzae, and Pseudomonas aeruginosa. Patients with CF have bronchiolitis and bronchiectasis and produce copious amounts of thick, mucoid secretions. Mucus sometimes obstructs the airways and causes atelectasis, pneumonia, or lung abscesses. As the disease progresses, the lungs become hyperinflated, and bronchiectatic exacerbations increase in frequency. Patients with end-stage CF have severe debility with marked hypoxemia and may develop pulmonary hypertension and cor pulmonale.

Diagnosis

The diagnosis of CF is suspected when a patient has clinical manifestations of the disease or has close family members with CF. Findings of recurrent pulmonary infections or failure to grow as rapidly as expected are clinical clues that often prompt physicians to initiate testing for CF. The diagnosis usually is confirmed with the sweat chloride test, which is done with electrical stimulation of the skin to produce sweat (iontophoresis). In a child, a sweat chloride level greater than 60 mEq/L confirms the diagnosis of CF.¹⁷⁹

Monitoring

The lung disease of CF is progressive. Careful monitoring of progression and response to treatment is routinely accomplished with spirometry and chest films. Cultures of sputum are often used to monitor for airway flora and resistance.

Treatment

The deficiency of pancreatic enzymes that occurs in patients with CF is managed with pancreatic enzyme supplementation. Several important steps are taken to help patients with CF maintain lung function. Regular chest physical therapy improves lung function and clearance of secretions.¹⁸⁰ When patients with CF become teenagers or young adults, they may have no partner to assist with chest physiotherapy. For these patients, strenuous exercise, external pneumatic vests,¹⁸¹ PEEP devices, or autogenic drainage may substitute for regular chest physiotherapy. Another mucus clearance adjunct is inhaled recombinant deoxyribonuclease (DNase or DNAase). The routine daily use of inhaled DNase reduces the frequency of respiratory infections.^182,183 The daily use of nebulized 7% saline both preserves lung function and decreases the likelihood of bronchiectatic flare-ups.¹⁸⁴

Antibiotics directed against the usual infectious organisms are required with each bronchiectatic exacerbation. As CF progresses, the bacteria causing exacerbations can become progressively more resistant to antibiotic treatments. Intravenous antibiotics are often required if a bronchiectatic exacerbation is caused by resistant bacteria. A nebulized form of the antibiotic tobramycin is used to prevent infection. When inhaled tobramycin is used twice daily every other month, there is a marked reduction in the number of bronchiectatic exacerbations.¹⁸⁵ The regular use of azithromycin helps preserve lung function and decreases the frequency of pulmonary flare-ups.¹⁸⁶

High doses of the antiinflammatory drug ibuprofen reduce the rate of lung function loss in patients younger than 13 years old.¹⁸⁷ Many patients with CF have asthma symptoms. These patients benefit from bronchodilators.

Lung transplantation is commonly performed in patients with advanced CF lung disease. Double-lung transplantation is the most commonly used form of lung transplantation in the treatment of patients with CF. New therapies for CF focus on improving the function of specific CFTR mutations.¹⁸⁸

Prognosis

When CF was first described more than 60 years ago, children with the disease rarely lived more than a few years. Today, median survival of patients with CF is nearly 38 years.¹⁷³