KEY POINTS
- 1.
Neonatal respiratory disease that requires surgery can have devastating consequences. Care for patients with these conditions involves a multidisciplinary team including neonatologists, pediatric surgeons, nurses, and respiratory therapists.
- 2.
These surgical respiratory defects include upper airway stenosis, laryngomalacia and tracheomalacia, congenital lung lesions, and the congenital defects of the diaphragm.
- 3.
Stridor is the most characteristic finding of upper respiratory obstructions. Acute obstruction may be asymptomatic or present with stridor, tachypnea, fatigue, nasal flaring, cyanosis, drooling, and use of accessory muscles. Chronic obstruction may present as failure to thrive and poor weight gain due to poor coordination between swallowing and breathing.
- 4.
Laryngomalacia is the most frequently seen congenital laryngeal anomaly and typically presents with stridor. It is characterized by an inward collapse of the supraglottic airway with inspiration. Laryngeal stenosis can occur in the supraglottic or the subglottic regions.
- 5.
Tracheomalacia is characterized by an increased collapsibility of the trachea. This is caused by structural anomalies of the tracheal cartilage or posterior membrane or by external vascular compression. In congenital tracheal stenosis the trachea is narrow due to complete, abnormal cartilaginous rings that result in stenotic segments.
- 6.
Abnormalities of the aortic arch and pulmonary vasculature can compress the airway and cause respiratory compromise. Patients present with noisy breathing, barking cough, recurrent respiratory tract infections, and dysphagia and may have episodes of apnea.
- 7.
Congenital lung lesions are a spectrum of developmental anomalies such as congenital pulmonary airway malformations, bronchopulmonary sequestrations, and congenital lobar emphysema. Other malformations include bronchogenic cysts, lymphangiomas, and pleuropulmonary blastomas.
- 8.
Congenital diaphragmatic hernia is a defect of the diaphragm through which any intraabdominal organ can protrude into the chest. It is intrinsically associated with lung hypoplasia and pulmonary hypertension beyond simple physical compression.
- 9.
Diaphragmatic eventrations are marked by an abnormal elevation of the hemidiaphragm. These can be congenital or acquired. Congenital diaphragmatic eventrations result from incomplete development of the central tendon or the muscular portion of the diaphragm.
Upper Respiratory Airway Disease
Diseases of the upper respiratory airway in infants can be classified according to their etiology as congenital or acquired. Acquired disease is more common and primarily associated with prolonged intubation, whereas congenital disease is associated with a developmental defect during gestation. In the neonate, this distinction may be hard to make because an acquired injury is commonly superimposed on a congenital abnormality. ,
Anatomically, the pediatric upper airway is similar to an inverted cone, with the trachea fitting into the cricoid above it, the cricoid into the thyroid cartilage, and the thyroid cartilage into the hyoid space ( Fig. 84.1 ). , The larynx of a term infant measures approximately 4.5 mm in the coronal plane and 7 mm in the sagittal plane. It allows for respiration and protection of the respiratory tract but also serves the secondary function of phonation through the use of the vocal cords. The narrowest point of the larynx is the subglottic space, measuring 4 mm across.
Clinical Characteristics
The presentation of upper airway disease is highly variable. Patients may be asymptomatic or present with stridor, tachypnea, fatigue, nasal flaring, cyanosis, drooling, and use of accessory muscles. Chronic obstruction may present as failure to thrive and poor weight gain due to poor coordination between swallowing and breathing.
Stridor is the most characteristic finding of upper respiratory obstructions. The types of stridor are based on the affected portion of the respiratory tree. Stridor during inspiration is characteristic of obstructions in the supraglottic region, whereas stridor during expiration is caused by lesions in the intrathoracic trachea or bronchi. Obstruction of the glottis or subglottis causes a biphasic stridor, heard during both inspiration and expiration. Emergent medical attention is warranted, because this form of stridor can quickly precede respiratory collapse.
Examination of a neonate in respiratory distress should begin with an evaluation for upper airway disease. The initial step is to access the acuity of respiratory compromise. If the airway is unstable, emergency airway access through endotracheal intubation or a surgical airway procedure (tracheostomy) is performed. If the child is stable, patient data can be gathered including history of prematurity, endotracheal intubation, or associated syndromes. Due to the location of the airway and gastrointestinal tract in relation to one another, difficulty swallowing or eating may be indicative of mediastinal masses, vascular rings, or other lesions such as a foreign body in the esophagus. Information concerning episodes of choking, coughing, or cyanotic spells during feeds also constitutes an important finding. ,
Diagnosis
Endoscopy
Evaluation of the upper airway is done through direct visualization or with endoscopic equipment. It may be performed on an awake child, which allows for functional and dynamic assessment of the larynx and vocal cords, or it can be done under sedation or general anesthesia, which is better suited for obstructive lesions and those further down the respiratory tract.
Endoscopic airway evaluation is ideally done in a setting with ample cooperation between the anesthesiologist, a nurse or surgical assistant, a pulmonologist, and the surgeon (ear, nose and throat [ENT] and/or pediatric surgeon). Assessment in the setting of respiratory compromise should be done efficiently and carefully. Any forceful contact with the upper airway mucosa may easily worsen the respiratory status. Instruments for urgent airway access should be easily available.
The visualization of the larynx, or laryngoscopy, is categorized according to whether the provider is directly viewing the larynx (direct laryngoscopy) or is viewing the larynx through a mirror or camera (indirect laryngoscopy). Awake, flexible fiberoptic laryngoscopy allows for assessment of dynamic airway collapse and vocal cord mobility. It may help evaluate the sinonasal cavity (nasolacrimal duct cysts and polyps, nasoseptal deviation), nasopharynx (choanal atresia, nasopharyngeal stenosis, adenoid hypertrophy), oropharynx (tonsil hypertrophy, pharyngomalacia), and larynx (laryngomalacia, vocal cord immobility).
Evaluation of the trachea and bronchi is performed with a bronchoscope. Flexible bronchoscopy allows for assessment of the distal airway. The standard pediatric flexible bronchoscope is 3.5 to 3.7 mm in diameter and can be used in patients who weigh as little as 700 g. Some of them can pass through tracheostomy tubes or endotracheal tubes and still allow for ventilation. Flexible bronchoscopy can be performed through the mouth or nare. This provides the advantage of evaluating patients with anatomic anomalies or maxillofacial trauma.
Rigid bronchoscopy permits detailed examination of the trachea and proximal bronchi and allows for the use of instruments through its larger ports. However, it can only be performed through the mouth and thus requires neck hyperextension. Children with physical conditions that cause decreased width of the mouth opening or decreased neck mobility are at higher risk of complications.
Endoscopic techniques are versatile procedures that not only allow for diagnosis through visual assessment, ultrasound evaluation, and biologic sampling but may also be therapeutic in certain situations. Laser fulguration with CO 2 , respiratory secretion clearance, and stent deployment are some therapeutic techniques. Additionally, when patient have worsening respiratory status, endoscopy can provide assistance for quick intubation or safe surgical airway access.
Imaging
Radiographic imaging can be performed depending on symptoms and may aid in the differential diagnosis. The soft tissue of the neck and chest is viewed in lateral and anteroposterior radiographs during both inspiration and expiration. Computed tomography (CT) scans and magnetic resonance imaging (MRI) can be used to delineate the anatomy and with contrast enhancement can help evaluate vascular structures or masses that may be compressing the airway.
Laryngomalacia
Laryngomalacia is the most common congenital laryngeal anomaly and the most common cause of stridor in infants. It is characterized by an inward collapse of the supraglottic airway with inspiration. , Symptoms may start shortly after birth with an average age of presentation of 2 weeks. Mild disease presents only as stridor, whereas moderate disease will also be accompanied by difficulty feeding. Ten percent of patients develop severe airway compromise, which requires surgical intervention.
Laryngomalacia is associated with several neonatal conditions. Gastroesophageal reflux is the most frequently associated comorbidity, with reported rates of up to 66%. Treatment for gastroesophageal reflux is therefore often required. Neurologic disease is also seen in 8% to 45% of children requiring operative management.
Awake flexible fiberoptic laryngoscopy is the standard for diagnosis because it allows for direct and dynamic visualization of the supraglottic airway. Radiographic techniques have little use but may rule out other pulmonary conditions.
The majority of patients with laryngomalacia have resolution of their symptoms with conservative management (speech therapy, acid suppression, and food thickening), with reports showing 80% to 90% resolution of symptoms within 4 to 42 months. , As the child grows, the airway enlarges and symptoms decrease. For patient with severe symptoms, surgical management is required. Supraglottoplasty is the surgical procedure of choice. It involves removing prolapsing supraglottic tissue with surgical instruments or endoscopically with CO 2 laser. ,
Laryngeal Stenosis
Stenosis of the larynx can be divided according to the area of involvement. It can occur in the supraglottis or the subglottis. The subglottis, the portion of the airway with the smallest diameter, is the most commonly involved. A lumen diameter less than 4 mm in full-term infants and less than 3 mm in preterm infants is considered stenotic.
Subglottic stenosis is the third most common congenital laryngeal anomaly in the newborn, after laryngomalacia and vocal fold paralysis, and is the most common acquired laryngeal anomaly. , It is caused by failure of recanalization of the airway by the 10th week of gestation or by iatrogenic injury due to placement of a large endotracheal tube. It is associated with trisomy 21, CHARGE syndrome, and 22q11 deletion syndrome. ,
As prolonged endotracheal intubation became more common for preterm infants, the incidence of subglottic stenosis increased. Reports from the 1960s saw rates ranging from 12% to 20% among patient with prolonged periods of intubation. Advances in intubation techniques and improved endotracheal tube care have decreased the incidence to 0.9% to 8.3%.
Mild cases can be managed conservatively, with the majority of patients outgrowing the condition. Severe cases require surgical intervention, usually by tracheostomy. Other management options include endoscopic balloon dilation and laryngotracheal reconstruction with cartilage graft. ,
Laryngeal Webs and Laryngeal Atresia
Laryngeal or glottic webs may be congenital or acquired. Congenital webs are associated with deletions of chromosome 22q11.2, and acquired lesions are caused by injury to the larynx. Given syndromic associations, patients should undergo evaluation for other anomalies.
Laryngeal webs are classified according to the degree of obstruction, with the most severe being total laryngeal atresia. Hoarseness is the most common symptoms seen in webs, whereas aphonia and rapid asphyxia are seen with atresia. Diagnosis is initially clinical and confirmed with endoscopic techniques.
Management goals are to address the obstruction and preserve phonation. If severe airway obstruction is present, tracheostomy is mandated and definitive management delayed. For mild laryngeal webs, endoscopic lysis with topical mitomycin is sufficient, but for more severe webs, laryngotracheal reconstruction may be required. Total atresia of the larynx causes congenital high airway obstruction syndrome in utero. This syndrome is generally lethal, but some reports of survival with fetal intervention have been reported. ,
Tracheomalacia
Tracheomalacia is a condition characterized by an increased collapsibility of the trachea. This is caused by structural anomalies of the tracheal cartilage or posterior membrane or external vascular compression ( Fig. 84.2 ). Patients with a history of tracheoesophageal fistula or those who undergo prolonged intubation have increased risk of developing this disease. ,
Symptoms generally only occur during periods of high respiratory demand. These symptoms consist of a brassy cough, expiratory stridor, and “dying spells” that happen during or immediately after feeding. Direct visualization via endoscopy is the gold standard for diagnosis, but CT and MRI are used as complementary studies to assess for external compression.
Symptoms of mild cases of tracheomalacia improve and resolve over the first year of life. Medical treatment with hypertonic nebulizers, inhaled steroids, and bronchodilators help manage symptoms. Continuous positive airway pressure is effective for moderate disease, and surgical interventions are reserved for patients with “dying spells,” recurrent infection, or difficulty extubating. ,
Historically, tracheostomy and mechanical ventilation were the mainstay treatment for patients with severe tracheomalacia. This approach has fallen out of favor due to the risks associated with long-term tracheostomy tube placement. Current management is individualized and depends on associated conditions (vascular compression, mediastinal masses, and presence of tracheoesophageal fistula). Surgical options include open or thoracoscopic aortopexy, tracheal resection with end-to-end anastomosis, slide tracheoplasty, and tracheopexy ( Fig. 84.3 ). ,
Intraluminal airway stenting has been used to decrease the effects of tracheal narrowing. Newer stents can be deployed into the airway endoscopically and require bronchoscopy and fluoroscopy to ensure the stent is appropriately placed to support the lumen best. Although stents to treat tracheomalacia seem promising, potential complications such as stent migration causing erosion or obstruction may be significant.
Tracheal Stenosis
The normal trachea has horseshoe-shaped cartilaginous rings and a posterior wall composed of connective tissue and the trachealis muscle. This morphology gives the trachea enough compliance to provide adequate ventilation. In congenital tracheal stenosis (CTS) the trachea is narrow due to complete, abnormal cartilaginous rings, which result in stenotic segments. , , CTS is associated with congenital vascular and cardiac malformations in 25% to 70% of cases and with lung hypoplasia and total lung agenesis.
Presentation of CTS is variable and depends on the degree of stenosis. It can present in the early neonatal period with stridor, cyanotic spells, and coarse cough or may develop later in childhood, associated with exercise-related respiratory difficulties. The stenotic segment does not necessarily produce immediate respiratory distress, but in the setting of mucosal edema, it may lead to acute airway obstruction and require surgical intervention.
Acquired tracheal stenosis is most frequently caused by an iatrogenic event that leads to inflammation, ulceration, and scarring. This is common in patients with underlying CTS, where an endotracheal tube of what would normally be an appropriate size for the age causes injury in a small airway.
Bronchoscopy yields a definitive diagnosis by confirming the presence of complete tracheal rings, whereas imaging techniques such as CT or MRI may provide information about the relationship of the mediastinal structures and the airway and can help rule out other diagnoses.
Patients with minimal symptoms can be managed expectantly, and serial examinations are done to assess tracheal growth. For patients with persistent symptoms, operative management is indicated. Intervention includes tracheal resection with end-to-end anastomosis, patch tracheoplasty, and slide tracheoplasty.
Vascular Compression of the Airway
Abnormalities of the aortic arch and pulmonary vasculature can cause compression of the airway and lead to respiratory compromise. Patients present with noisy breathing, barking cough, recurrent respiratory tract infections, and dysphagia and may have episodes of apnea. Diagnostic workup includes chest radiograph, CT scan with contrast enhancement, bronchoscopy, and echocardiogram. The most common causes of vascular airway compression are innominate artery compression syndrome and vascular rings.
Innominate artery compression syndrome occurs when there is anterior compression of the trachea by the innominate artery as it crosses from left to right prior to originating from the aorta. Surgical therapy for severe disease involves suspending the innominate artery anteriorly by suturing it against the posterior sternum. Improved diagnostic techniques have facilitated better patient selection and an overall decrease in the number of procedures performed, along with improved outcomes.
The most common vascular rings are the double aortic arch, the right aortic arch, and the pulmonary artery sling. In a double aortic arch, the aorta divides into two branches, one anterior and one posterior to the esophagus and trachea, and these join posteriorly to form the descending aorta. Patients with a right aortic arch have an aortic arch that courses to the right of the trachea and esophagus. The left subclavian artery arises posterior to the esophagus and a persistent ligamentum arteriosum connects to the descending aorta, coursing anterior to the trachea and forming a ring. A pulmonary artery sling is formed by an anomalous course of the left pulmonary artery in which the artery arises from the right pulmonary artery and courses posterior to the right mainstem bronchus and trachea before reaching the left pulmonary hilum. Treatment of vascular rings is surgical and commonly requires clamping, division, and reimplantation of these vessels by a pediatric cardiothoracic surgeon.
Congenital Lung Lesions
Congenital lung lesions are a spectra of developmental anomalies of the bronchopulmonary unit. Multiple variations exist including congenital pulmonary airway malformation (CPAM), bronchopulmonary sequestration (BPS), and congenital lobar emphysema (CLE). Other malformations include bronchogenic cysts, lymphangiomas, and pleuropulmonary blastomas. ,
Clinical Characteristics
The majority of these lesions cause no impact on fetal development, they are diagnosed incidentally during routine prenatal evaluation and remain stable or regress. , Lesions that progressively enlarge may be associated with lung hypoplasia and mediastinal shift, which can lead to cardiac failure and subsequently to hydrops fetalis. Hydrops fetalis is the most important predictor of poor perinatal outcome in these patients.
Delivery is usually uncomplicated, and more than 70% of neonates are asymptomatic. Those few with symptoms may require ventilatory support. Although infrequent, symptoms beyond the neonatal period are related to recurrent respiratory tract infections, chronic cough, and wheezing. More severe variants may present as pneumothorax, hemothorax, air embolism, or high-output cardiac failure due to shunting via collaterals.
Diagnosis
Prenatal
Serial fetal ultrasounds are done to assess the size, location, and progression of the lesion. These lesions are cystic or solid lesions and can be divided morphologically into two categories: (1) macrocystic lesions (with at least one cyst greater than 5 mm) and (2) microcystic lesions (seen as a solid mass) ( Fig. 84.4 ).
Additionally, ultrasound permits characterization of the lesion and fetus to predict prognosis. Prognostic ultrasound markers include mediastinal shift, diaphragmatic eversion, polyhydramnios, ascites, pleural effusion, and, importantly, lesion size.
The size of the lesion is best understood in relationship to the size of the rest of the fetus. This is performed by comparing the volume of the lesion to the head circumference of the fetus, which is called the cyst volume-to-head circumference ratio (CVR). A CVR greater than 1.6 before 24 weeks of gestation has been associated with an 80% risk of developing hydrops fetalis. Prenatal characteristics of high risk include a CVR greater than 1.6, placentomegaly, abnormal fetal echocardiography, diaphragm eversion, or severe mediastinal shift. , Fetal MRI is currently used in some centers to describe the lesions and may also help characterize other associated findings such as pulmonary hypoplasia.
Postnatal
Once the infant is born, a thorough physical exam is performed. Chest radiograph has a low sensitivity but may show a mediastinal or lung field mass. CT scan and MRI with contrast enhancement may aid in identifying the anatomy and vasculature. Pathologic analysis after resection provides definitive diagnosis.
Management
Prenatal
Prenatal management of all congenital lung lesions follows the same algorithm. Management considers the viability of the fetus, gestational age, CVR, and risk of developing hydrops fetalis. For patients with a low risk of developing hydrops fetalis (CVR ≤ 1.6), serial ultrasound monitoring and elective resection after term delivery are indicated.
High-risk patients (CVR > 1.6, placentomegaly, severe mediastinal shift, diaphragm eversion, or lung hypoplasia) are managed differently depending on the morphologic characteristics. If microcystic, administration of maternal betamethasone has shown to increase survival, reverse hydrops, and decrease fetal surgical interventions. , In contrast, macrocystic lesions have not been shown to benefit from maternal steroids treatment.
Fetuses who despite conservative or medical management continue to have worsening CVR or hydrops fetalis progression may benefit from fetal interventions. These include prenatal cyst decompression or open fetal surgery. When patients have high postnatal survival probability or are born at more than 32 weeks of gestation, ex-utero intrapartum treatment (EXIT) procedure and resection after induced preterm delivery may be done. ,
Prenatal cyst decompression is achieved by transamniotic needle decompression or thoracoamniotic shunt, with evidence suggesting improved survival. Fetal lobectomy is a last-resort option for refractory lesions, with a few case series reporting resolution of hydrops and return of the mediastinum to midline after the procedure. Survival in these series is a maximum of 50% but comes at the cost of significant maternal morbidity and prematurity.
Postnatal
Postnatal management is determined based on time of diagnosis and symptom presentation. Initial management relies on ventilatory support for symptomatic patients and chest tube placement for pleural complications. Vasopressor support and/or extracorporeal membrane oxygenation (ECMO) are rarely required. When pulmonary hypoplasia is present, surgical intervention can be delayed until the patient is stable.
With a few exceptions, complete resection is the goal, and this can be accomplished via thoracotomy or video-assisted thoracoscopic surgery. In a meta-analysis comparing thoracoscopic versus open resection, there were no significant differences in complication rates. Length of stay and chest tube duration were longer in the thoracotomy group.
Lobectomy has been the standard technique for resection of congenital lung lesions. Lung-sparing resection techniques have been studied as a feasible and safe approach, but current evidence provides no information about benefits for long-term pulmonary function and superiority to standard lobectomy. , Wedge resection is considered in cases of bilateral or multiple lobe involvement.
Congenital Pulmonary Airway Malformation
CPAM is a developmental anomaly of the lower respiratory tract that has an unspecified origin and is relatively uncommon. Given advances in prenatal diagnosis, early and accurate identification is becoming more common, and some authors posit that the incidence will continue to rise. Current studies show incidences between 1 in 7000 and 1 in 35,000. ,
CPAMs are characterized by proliferation of immature bronchiolar structures localized to an area of the lung. They have a small communication path with the tracheobronchial tree and receive and drain blood through the pulmonary circulation in most cases. Some may have an additional arterial supply from systemic branches, the most common being from the abdominal aorta. Lesions with combined pulmonary and systemic vasculature are called hybrid lesions.
Lesions can affect any part of the lung and are found in the left and right sides equally. Unilobar cases account for 80% to 95% of presentations, with the remaining few being bilateral (2%) and even fewer involving more than one lobe of one or both lungs.
Treatment of asymptomatic CPAM is controversial. Arguments in favor of early surgical treatment are higher rates of infection in patients with CPAM and an association with lung malignancies such as bronchoalveolar carcinoma and pleuropulmonary blastoma. Conservative management relies on CT scans for monitoring increasing radiation exposure. A 2016 meta-analysis of retrospective studies comparing conservative management and surgical resection for asymptomatic CPAM concluded that resection was safe and prevented the risk of symptom development, albeit with increased morbidity compared with nonsurgically managed patients. The treatment of choice for symptomatic CPAM is a lobectomy of the involved lobe.
Bronchopulmonary Sequestration
Bronchopulmonary sequestrations represent 10% of diagnosed congenital lung lesions. They are characterized by a lower respiratory tract mass that has no communication with the tracheobronchial tree and receives systemic arterial supply but may have systemic and/or pulmonary venous return.
The two main forms of BPS are intralobar sequestration (iBPS) and extralobar sequestration (eBPS). iBPS (75% of cases) has venous return to the pulmonary veins and shares the same visceral pleura as its adjacent normal lung lobe, whereas eBPS (25% of cases) may have systemic or pulmonary venous return and has its own distinct pleura. The etiology of eBPS differs from iBPS by arising from an abnormal budding in the early foregut development.
In a 2019 case series of 208 patients with BPS, eBPS was most frequently located in the paraspinal region and more commonly in the left lower thorax, although a few cases were located in the right side and middle or upper thorax, diaphragm, abdomen, and neck. iBPS was uniformly found in lower lobes. This is consistent with previous literature. eBPS is managed differently than CPAM. Studies suggest that serially followed eBPS lesions decrease over time. They also have less reported infection incidence and malignancy risk; therefore it is safer to follow lesions without surgical intervention. , Surgical management of eBPS consists of ligation of the feeding vessel and removal of tissue via thoracoscopy.
Given that iBPS is more involved with the lung parenchyma, has high output physiology, and has a higher risk of infection, postnatal lobectomy is generally recommended.
Congenital Lobar Emphysema
CLE is a rare (1 in 20,000 to 1 in 30,000 live births) anomalous lung development disease that results in hyperinflation of one or more lobes of the lung. It is more common in males than females in a ratio of 3:1.
Although the developmental mechanism has not been completely defined, it seems that CLE arises from localized malformations that result in overinflation of the lung segment. Inappropriate bronchial valvular mechanisms (one-way valves), obstructive processes, or a polyalveolar lobe are possible explanatory causes. ,
Obstruction of the airway during development is seen in 25% of cases. The obstruction results in air trapping and histologic changes of the alveolar distension without structural anomaly. CLE with a polyalveolar lobe occurs in up to one-third of cases and is characterized by a three- to five-fold increase in the number of alveoli without changes in the bronchial branches. Studies suggest that a polyalveolar lobe may be a normal reaction of the parenchyma distal to a complete bronchial obstruction during gestation.
Upper lobe involvement occurs on the left in 40% to 50% of patients and on the right in 20%. The right middle lobe is involved in 25% to 30% of patients, and lower lobe involvement is extremely rare (2%–5%). ,
Clinical Presentation
Many patients with CLE present with respiratory distress, although a significant number can also be asymptomatic or display evidence of mild tachypnea. Subtle signs of increased work of breathing can include feeding difficulties and poor weight gain. In patients who develop respiratory distress, symptoms occur immediately after birth or up to 4 months of age. Rapidly progressing respiratory failure is expected in symptomatic neonates and warrants emergency thoracotomy in 10% to 15% of cases. Neonates can have a shift in apical cardiac impulse to the contralateral side, decreased breath sounds in the affected hemothorax, and hyperresonance to percussion.
Diagnosis
CLE is not associated with significant prenatal findings. Ultrasound may show retained fluid, which develops into trapped air postnatally. This can cause mediastinal shift.
Chest radiograph can show an opaque mass if there is an obstructive etiology, but it can also show an air-trapping pattern. Mediastinal and tracheal shift, compression and collapse of ipsilateral unaffected lobe(s), and flattening or inversion of the ipsilateral diaphragm may also be present.
Management
In asymptomatic patients, no resection is required and patients may be safely followed leading to spontaneous regression. Surgical treatment is not warranted in cases where CLE is caused by cartilaginous weakness of lobar bronchus, cases of mucous plugs, or cases of viral bronchiolitis, because they can resolve spontaneously over time. When CLE is caused by a bronchogenic cyst, the cyst may be excised while retaining the affected lobe.
Neonates with severe symptoms require immediate surgical intervention, while a delayed approach can be offered in those infants with milder manifestations. Surgery should be performed as soon as possible to avoid increased risk of infection or respiratory distress and to allow for maximum compensatory lung growth. The gold standard of surgical therapy is a formal lobectomy.
Bronchogenic Cysts
Bronchogenic cysts originate from an abnormal budding of the fetal tracheal diverticulum or the primitive foregut. They may communicate with the tracheobronchial tree and may be located anywhere along the respiratory apparatus. They do not have bronchial vascular development. Histologically they have cartilage, smooth muscle, and epithelial glandular tissue. Enlargement of these cysts can cause bronchial obstruction and dilate the lung distally.
Diagnosis
Prenatal diagnosis is infrequent but can potentially be seen as a unilocular fluid-filled cyst in the middle posterior portions of the mediastinum with distal lung dilation. Postnatal chest radiograph may show a mediastinal or lung mass. This can be followed up by a bronchoscopy and CT scan for further evaluation. Echocardiography should also be performed to eliminate other diagnoses including pericardial cyst.
Management
The goal of treatment is to decrease the risk of infection, airway compromise, and impingement on the trachea, bronchus, heart, or esophagus or if the etiology of the mass is unknown.
Surgical resection is performed based on the location of the cyst and adjacent structures. Cross-field ventilation or cardiopulmonary bypass is reserved in the case of cystic involvement with the trachea or mainstem bronchi, which is extremely rare. Thoracotomy or thoracoscopic excision of the cyst are the procedure of choice.
Congenital Diaphragmatic Hernia
A congenital diaphragmatic hernia (CDH) is a defect of the diaphragm through which any intraabdominal organ can protrude into the chest. CDH is thought to be a systemic disease that involves a field defect of the diaphragm and/or lungs. It is intrinsically associated with lung hypoplasia and pulmonary hypertension (PHTN) beyond simple physical compression. Furthermore, CDH is often part of a syndrome that involves multiple anomalies in other systems. Treatment is therefore complex and usually requires a multidisciplinary team to care for its components.
CDH occurs between 2.3 and 2.4 per 10,000 live births, , and despite advances during the past two decades, it continues to have mortality of 20% to 30%. Nevertheless, recent data obtained from centers with focused CDH care report survival rates as high as 90% in severe cases, which emphasize the importance of standardizing care to achieve similar results in all centers.
Anatomy and Embryology
The earliest evidence of a diaphragm precursor is seen during the fourth week of gestation. The diaphragm is thought to develop from the interaction of several embryonic components. The septum transversum is located ventrally; it is the precursor of the central tendon. Dorsolaterally are the pleuroperitoneal folds and dorsally, the crura of the esophageal mesentery. These form the crural and dorsal structures. ,
These structures interact, surround the developing foregut, and start separating the pleuropericardial and peritoneal cavities to form the primitive diaphragm. At week 6, the communications between the pleural and peritoneal cavities begin to close as the pleuroperitoneal membranes develop. By week 8, the pleural and peritoneal cavities are separated. Muscularization then occurs, with migration of phrenic nerve axons and myoblasts from cervical segments to form the mature diaphragm.
Current theories explaining the pathogenesis include failure of muscularization of the diaphragm prior to closure of the pleuroperitoneal canals; this causes a weakness in the diaphragm, protrusion of intraabdominal organs, and mechanical compression of the developing lung, leading to lung hypoplasia. Other authors have postulated that the abnormal lung development is part of an overall field defect and is not dependent on a mechanical effect of the bowel; this may lead to a weakened posthepatic mesenchymal plate and impaired diaphragm fusion. More recently, the role of the muscle connective tissue fibroblasts derived from the pleuroperitoneal folds has been associated with the morphogenesis of the diaphragm; mutations in these cells might contribute to abnormal diaphragmatic development. ,
CDH affects the left side in 80% to 85% of cases and the right side in 10% to 15% of cases, with the remaining few cases being bilateral. Approximately 90% are posterolateral, passing through a defect caused by failure of fusion of the pleuroperitoneal folds and the transverse septum with the intercostal muscles, known as Bochdalek hernias. Ten percent are anterior and are caused by failure of fusion of the transverse septum and the lateral body wall; these are Morgagni hernias. , ,
Pathophysiology
The main pathophysiologic components of CDH are pulmonary hypoplasia and PHTN. Pulmonary hypoplasia is characterized by a uniform loss of pulmonary mass, bronchial branching, decreased alveolar to arteriolar ratios, abnormally thick-walled arterioles, and decreased vasoreactivity. This is caused by arrest of alveolar development at the midcanalicular stage of lung embryogenesis and is directly related to mortality, long-term morbidity, and limited quality of outcome from CDH.
The pulmonary vasculature during the last weeks of gestation is a high-resistance, low-flow system. As the child is born, it transitions into a low-resistance, high-flow system in the first months of life. In patients with CDH there is evidence of increased arteriolar muscularization and decreased pulmonary artery density, which causes persistence of the high pulmonary vascular resistance. Severity of CDH-associated PHTN tracks with overall morbidity and mortality. Some studies show that persistent suprasystemic pulmonary artery pressures after 3 weeks of life had a mortality rate of 100%.
Diagnosis
Prenatal Diagnosis
Prenatal evaluation provides an important aspect of the care of patients with CDH. It estimates prognosis and is an adjunct to prenatal counseling, triage, and future management. Similar to other congenital diseases, a high index of suspicion for other anomalies should be considered and worked up.
Up to 40% of CDH cases have at least one additional congenital anomaly, and 30% have a causative genetic variation. , Thirty percent will present with cardiovascular anomalies, the most common being left ventricular hypoplasia, followed by atrial septal defect. Eighteen percent will be urogenital, 15% musculoskeletal, and 10% neurological. CDH is also associated with other gastrointestinal complications such as malrotation and accessory spleen.
Although rare, hydrops can also develop from herniation of intraabdominal organs into the thorax by causing mediastinal shift and cardiac failure. Prognosis is poor for these patients.
Fetal Ultrasound
Ultrasound is the standard modality for diagnosis of CDH. It can assess lung size, liver position, stomach position, and associated congenital anomalies. Recent data estimate that it has a prenatal detection rate of greater than 60%, with more severe forms having detection rates of up to 75% in high-volume centers. ,
With current fetal ultrasound techniques, diaphragmatic hernias can be identified as early as 14 to 15 weeks of gestation. Herniated bowel appears as heterogenous echoes in the thoracic cavity, and by week 18 it is possible to see an incomplete diaphragm. The presence of gastric bubbles above the diaphragm and a small abdominal circumference can also be detected.
Herniation of the stomach may lead to kinking and obstruction of the upper gastrointestinal tract, which can be seen as polyhydramnios. Mediastinal shift can also be present, and although it is not specific for CDH, it may help differentiate between left- and right-sided hernias.
Ultrasound plays an important role in risk stratification. The most common predictors of postnatal survival are liver herniation into the thorax and the fetal lung volume, which is assessed by measurement of the observed to expected lung-to-head circumference ratio (O/E LHR). ,
The LHR is the ratio between the lung area and the head circumference. On ultrasound the lung area is measured in the hemithorax contralateral to the hernia at the level of a four-chamber view of the fetal heart in cross-section images. An O/E LHR less than 25% has a historically predicted survival rate from 12.5% to 30%, whereas an O/E LHR greater than 35% historically predicts a survival rate of 65% to 88%.
Disadvantages of fetal ultrasound include its user dependence. Efforts are currently being made to standardize prenatal ultrasound assessment of the fetus.
Fetal Magnetic Resonance Imaging
MRI has been shown to enhance prenatal evaluation. It is less user dependent and is less affected by maternal body habitus and fetal movements. It provides specific anatomic detail of the diaphragm defect, hernia location, hernia contents, and surrounding structures. ,
Ultrafast fetal MRI has also proven useful in predicting outcomes for some patients with CDH. It provides accurate measurement of the liver-to-diaphragm ratio and may also assist in the quantification of pulmonary hypoplasia by measurement of the observed to expected total fetal lung volume.
The liver-to-diaphragm ratio is a surrogate for severity of herniation, and a high ratio is associated with worse outcomes. Likewise, a 2017 meta-analysis showed statistical differences between the mean MRI-calculated total fetal lung volume for survivors with CDH versus those who did not survive.
Postnatal Diagnosis
Respiratory distress is the most common symptom after birth, although some patients may be asymptomatic. The hypoxia does not progress over time but instead appears suddenly and rapidly after a period of good ventilation and oxygenation. As the neonate takes a breath, distension of the stomach and intestine occurs, causing compression of the thoracic cavity and mediastinum.
On physical exam, patients will have absent or decreased breath sounds on the ipsilateral side. Severe herniation of the abdominal viscera presents as a barrel chest with a scaphoid abdomen. The point of maximal cardiac impulse may be displaced if there is mediastinal shift.
Postnatal diagnostic confirmation is achieved by chest radiography to visualize the intrathoracic intestinal loops, nasogastric tube curled up in the chest, absence of a diaphragmatic shadow on the herniated side, mediastinal and cardiac shift toward the contralateral side, and possibly intrathoracic herniation of the left lobe of the liver.
Management
Prenatal Care
Patients with CDH should be managed by obstetricians in a tertiary perinatal center in consultation with both pediatric surgeons and neonatologists. Other specialists to include in the consultation process are geneticists, financial counselors, and social workers.
Once the diagnosis is made with a screening prenatal ultrasound, an advanced fetal ultrasound is carried out with assessment of morphologic parameters, associated anomalies, anatomic characteristics of the diaphragmatic hernia, and risk stratification.
Patients with isolated CDH have considerably higher survival rates than patients with associated anomalies. , Given the high association with chromosomal abnormalities, genetic consultation with karyotype analysis should be considered. Identification of a genetic component may provide important information regarding prognosis and future management. Chromosomal anomalies, lethal syndromes, and other negative predictors are to be identified and shared to allow parents to make an informed decision about their pregnancy.
Prenatal therapy with medications has been pursued with the hope of minimizing the development of lung hypoplpasia and pulmonary hypertension. Although there is evidence for the use of prenatal steroids for lung maturity and development in prematurity, this effect was not seen in CDH. , Sildenafil is a drug commonly used for the treatment of PHTN postnatally. It is currently in consideration for clinical trials in prenatal CDH. Current studies are also targeting vitamin A, glucagon-like peptide-1 agonists, and tyrosine kinase inhibitors as potential therapeutic options.
Prenatal Interventions
Current fetal interventions mainly target improving lung hypoplasia and PHTN and not in utero repair of the diaphragm. In the 1980s, open fetal diaphragmatic repair was performed with the hypothesis that fetal reduction and closure of the hernia before week 24 of gestation would improve lung development. Subsequent prospective studies showed that fetuses undergoing fetal repair had higher complication rates without improvements in survival compared with the standard postnatal care. These interventions are therefore currently not performed. ,
Although open fetal surgery provided no benefits, minimally invasive procedures are currently being studied as possible options. Fetoscopic tracheal occlusion (FETO) was first conceptualized in the 1970s as a method of improving lung hypoplasia. It is a technique that has evolved and currently involves use of single-port fetoscopy to deploy a detachable balloon endotracheally between weeks 27 and 32 of gestation. The LHR is monitored to assess for lung hypoplasia improvement, and the balloon is removed 5 to 7 weeks after placement. FETO increases tracheobronchial pressure, leading to increased lung-branching morphogenesis and inducing lung hyperplasia.
The first experiences of outcomes for FETO show promising results. In patients with severe CDH with an expected survival of 0% to 24%, there were observed survival rates after intervention of 35% to 49% (LHR < 1.0). Other studies showed survival rates of 73%, although expectant management achieved a survival rate of 77% (LHR < 1.4). Refinements in patient selection and inclusion criteria may provide additional information about which patients can benefit from this procedure. The Tracheal Occlusion to Accelerate Lung Growth (TOTAL) trial, which started in 2011 and is still ongoing, aims to address these questions.
Postnatal Care
Immediate cardiopulmonary resuscitation is the initial postnatal goal. Priorities are maintaining adequate oxygenation and perfusion, minimizing acidosis, managing PHTN, and supporting cardiac output. Once the patient is stable, operative repair of the diaphragmatic hernia is performed.
Cardiopulmonary Resuscitation
Respiratory support is provided immediately with endotracheal intubation, mechanical ventilation, and placement of a nasogastric tube for foregut decompression. Preductal and postductal oxygenation monitoring allows for assessment of systemic and cerebral perfusion in the setting of persistent fetal circulation, and acid-base balance measurement assists in titration of mechanical ventilation.
The goal for mechanical ventilation is to maintain oxygenation while limiting the risks of ventilator-induced lung injury and alveolar instability. Fractional inspired oxygen is titrated to an oxygen saturation goal of above 80% and respiratory rates of 40 to 60 breaths per minute to target a partial pressure of CO 2 of less than 70 mm Hg and a pH above 7.2. Low inspiratory peak airway pressures of less than 25 cm H 2 O minimize volutrauma and barotrauma. ,
High-frequency oscillatory ventilator (HFOV) strategies are employed when conventional ventilation does not reverse hypercapnia and hypoxemia. Nevertheless, a randomized controlled trial done in 2016 comparing HFOV and conventional mechanical ventilation showed no clear superiority between strategies, with small advantages toward conventional mechanical ventilation.
Management of Pulmonary Hypertension
Gentle ventilatory parameters will help minimize hypoxia and acidosis, which are paramount for treating PHTN. Several studies outline the importance of prompt management of PHTN. Patients who developed normal pulmonary artery pressures of less than 50% systemic pressure by the first 3 weeks of life were found to have a 100% survival rate. In the same vein, patients with PHTN at 4 weeks of age had a high risk of death.
Assessment of PHTN and cardiac function is best done through the use of echocardiography. It is used to identify the presence of any cardiac anomalies and measure right and left ventricular function, pulmonary artery flow, and level of right-to-left shunt through a patent ductus arteriosus and patent foramen ovale. This provides information about the severity of PHTN and left ventricular function.
Strategies to improve PHTN include targeted vasodilation of the pulmonary vasculature and minimizing the pressure overload on the right ventricle.
Options that target pulmonary vasculature include inhaled nitric oxide (iNO) and sildenafil. A recent review for iNO showed no decreased mortality or need for ECMO in patients with CDH-associated PHTN, and therefore the study group recommended its use only in infants with hypoxic respiratory failure from etiologies other than CDH. Sildenafil has shown evidence of improving oxygenation and avoiding ECMO in the setting of PHTN that is refractory to iNO therapy. Bosentan, an endothelin-1 receptor antagonist, has been used for treatment of PHTN, but there is limited evidence of its efficacy in CDH.
Closure of the ductus arteriosus in the setting of PHTN may cause an acute decrease in systemic perfusion of previously stable patients. The closure prevents offload of the right ventricle, leading to progressive right heart dysfunction. To decrease the right ventricle overload, prostaglandin E1 analogs may be used to reopen the ductus arteriosus and improve right ventricle pressures.
In patients with left ventricular dysfunction, inotropic agents such as dopamine, dobutamine, epinephrine, and milrinone may increase left ventricular output and increase systemic pressure, minimizing right-to-left ductal shunting.
In patients with continued respiratory failure despite medical management, ECMO is a viable option. It is indicated for patients with continued respiratory failure, for prevention of ventilator-induced barotrauma, and for unstable patients with adequate lung parenchyma and potentially reversible PHTN. Venovenous or venoarterial ECMO are both equal options. Patients with CDH who undergo ECMO have survival rates of 30% to 50%. ,
Surgical Management
There are several options for operative repair of CDH. It can be open or minimally invasive. A subcostal approach is the most common open repair, whereas a thoracoscopy is the most common minimally invasive approach ( Fig. 84.5 ). Comparing benefits of minimally invasive with open procedures proves difficult, because minimally invasive techniques are reserved for patients within a lower risk category, whereas open procedures are reserved for higher risk patients. The approach mostly depends on center experience and careful patient selection.
