Pediatric Congenital Diaphragmatic Hernia Treatment & Management

Ideally, fetuses carrying a diagnosis of congenital diaphragmatic hernia should be delivered at an extracorporeal membrane oxygenation (ECMO) center and managed by an expert multidisciplinary team. ^[18]

Guidelines for ECMO consultation are available from the Extracorporeal Life Support Organization (ELSO), including 2020 guidelines for neonatal respiratory failure ^[13] and ECMO in coronavirus disease 2019 (COVID-19) patients. Baseline criteria for ECMO consideration include evaluation for risk factors because of the invasive nature of the therapy and need for heparinization. Although criteria are center-specific, infants should generally be older than 34 weeks' gestation, have a weight greater than 2000 g, have no major intracranial hemorrhage on cranial sonography, have been on mechanical ventilator support for fewer than 10-14 days, and have no evidence for lethal congenital anomalies or inoperable cardiac disease.

A 2020 review of the literature to determine whether congenital diaphragmatic hernia repair outcomes are better before or after decannulation in infants requiring ECMO led investigators to conclude the following ^[12] :

• Infants with congenital diaphragmatic hernia who require ECMO should undergo a trial of weaning with the goal of post-decannulation repair. There is an association with improved survival, shorter ECMO duration, and fewer bleeding complications.
• If these infants cannot be weaned off ECMO, the ideal time for repair is early on ECMO (≤72 hours of cannulation), which is associated not only with improved survival, less bleeding, and shorter ECMO duration but also with fewer circuit changes relative to late on-ECMO repair.
• Factors associated with reduced bleeding risk with on-ECMO repairs include following anticoagulation protocols and close perioperative monitoring of coagulation parameters.

Transfer

Sometimes stabilization for transfer can be very challenging. Timing is always difficult, but referral and transfer should occur prior to refractory hypoxia. Early consultation and discussion with the ECMO center is strongly recommended.

Because of associated persistent pulmonary hypertension of the newborn (PPHN) and pulmonary hypoplasia, medical therapy in patients with congenital diaphragmatic hernia (CDH) is directed toward optimizing oxygenation while avoiding barotrauma. ^[1]

In the delivery room, if the infant is known or suspected to have congenital diaphragmatic hernia, immediately place a vented orogastric tube and connect it to continuous suction to prevent bowel distension and further lung compression. For the same reason, avoid mask ventilation and immediately intubate the trachea. Avoid high peak inspiratory pressures and be alert to the possibility of early pneumothorax if the infant does not stabilize. ^[19]

Infants with congenital diaphragmatic hernia may have immature lung development, and animal studies have indicated that surfactant deficiency may be present. However, reports from the Congenital Diaphragmatic Hernia Study Group indicate that administration of exogenous surfactant does not improve survival, need for extracorporeal membrane oxygenation (ECMO), or long-term outcome. Interestingly, this finding is true for both term and preterm infants with congenital diaphragmatic hernia.

Mechanical ventilation strategies are targeted at avoiding high peak inspiratory pressures and synchronizing ventilation with the infant's respiratory effort. In some instances, high-frequency ventilation (HFV) may be helpful in avoiding the use of high peak inspiratory pressures, although this modality is best used at a center with experience in assessing and maintaining optimal lung distension.

Infants with congenital diaphragmatic hernia are critically ill and require meticulous attention to detail for subsequent medical care, including continuous monitoring of oxygenation, blood pressure, and perfusion. A minimal stimulation approach that reduces handling and invasive procedures, such as suctioning, is suggested.

Maintain glucose and ionized calcium concentrations within reference range. If necessary, support blood pressure using volume expansion and inotropic agents. An adequate circulating volume is necessary to maintain right ventricular filling and cardiac output; however, once circulating volume is normalized, repeated boluses of crystalloid solutions, colloid solutions, or both do not provide additional benefit. Inotropic support with dopamine, dobutamine, or milrinone may be helpful in maintaining adequate systemic blood pressure; dobutamine and milrinone may be particularly helpful if myocardial dysfunction is present. Epinephrine infusions may be necessary in severe cases; low-dose epinephrine (< 0.2 mcg/kg/min) may help to promote pulmonary blood flow and improve cardiac output.

The appropriate targets for PaO₂ and PaCO₂ are controversial. PaO₂ concentrations greater than 50 mm Hg typically provide for adequate oxygen delivery at the tissue level. Aiming for higher PaO₂ concentrations may lead to increased ventilator support and barotrauma. Similarly, infants with congenital diaphragmatic hernia often have hypercarbia because of pulmonary hypoplasia. Whether to maintain a low PaCO₂ for pulmonary vasodilation, to allow permissive hypercapnia, or to maintain normocarbia remains controversial. No reliable controlled studies are known, and debate continues in the medical literature. Retrospective studies suggest that gentle ventilation and allowing chronic mild hypercarbia may be associated with improved survival.

Alkalinization was frequently used in the past because of its ability to produce a rapid pulmonary vasodilation. Forced alkalosis can be accomplished either by using hyperventilation to induce hypocarbia or by alkali infusions. However, benefits of alkalosis have never been demonstrated in any prospective clinical trial, and these therapies are considered controversial. In addition, alkalosis may result in undesirable side effects. For instance, hypocarbia constricts the cerebral vasculature and reduces cerebral blood flow. Extreme alkalosis and hypocarbia are strongly associated with later neurodevelopmental deficits, including a high rate of sensorineural hearing loss. Previous studies by Walsh-Sukys and colleagues indicates that the use of alkali infusions may be associated with increased use of ECMO and an increased use of oxygen at age 28 days. ^[20]

Inhaled nitric oxide has revolutionized the treatment of PPHN but its benefit in the infant with congenital diaphragmatic hernia remains controversial. ^[21] Nitric oxide does not reduce mortality or the need for ECMO in infants with congenital diaphragmatic hernia, although it may immediately stabilize infants with critical hypoxemia and reduce the chances of cardiopulmonary arrest. ^{[21, 22]} Inhaled nitric oxide should be used with caution if ECMO is not immediately available. Newer studies indicated a potential role for long-term low-dose inhaled nitric oxide therapy in the treatment of late or recurrent pulmonary hypertension.

Sedation is an important adjunctive therapy, but the use of paralytic agents remains highly controversial. Although diminished swallowing may be beneficial, paralysis may promote both atelectasis of dependent lung regions and ventilation-perfusion mismatch, as well as generalized edema and decreased chest wall compliance.

Pulmonary care in congenital diaphragmatic hernia (CDH)

Severely affected infants have chronic lung disease. These infants may require prolonged therapy with supplemental oxygen and diuretics, an approach similar to that for bronchopulmonary dysplasia. The use of steroids, particularly high doses for prolonged periods, is controversial and may hinder appropriate lung and brain development.

Late pulmonary hypertension has been successfully treated with low-dose inhaled nitric oxide. ^{[20, 23]} This therapy can be delivered via nasal cannula following extubation. In this setting, the delivered dose is diluted because of entrainment of room air. In one report, the median duration of treatment using inhaled nitric oxide delivered via nasal cannula was 17 days. ^[24]

Case reports are now emerging regarding the use of other pulmonary vasodilators, such as sildenafil and endothelin receptor antagonists. Systemic study is required to assess the sustained benefit.

Neurologic evaluation

Following recovery, a neurologist or developmental pediatrician should perform an examination that includes an evaluation for CNS injury using head CT scanning or MRI.

The incidence of hearing loss appears to be particularly high in patients with congenital diaphragmatic hernia (approximately 40% of infants). An automated hearing test should be performed prior to discharge.

Gastroesophageal reflux

The incidence of significant gastroesophageal reflux  is very high in patients who survive congenital diaphragmatic hernia, and studies document an incidence of 45-85%.

The need for a diaphragmatic patch may be a significant predictor of gastroesophageal reflux. Severe reflux may result in chronic aspiration and is, therefore, aggressively treated.

Although most infants can be medically treated with H2-blockers or proton pump inhibitors in combination with a motility agent such as metoclopramide, surgical intervention is sometimes required.

Theoretically, fetal surgery for congenital diaphragmatic hernia provides an elegant solution to the difficult problem of congenital diaphragmatic hernia. Unfortunately, this is far from reality. Harrison et al reported the first human fetal surgery for congenital diaphragmatic hernia in 1990. However, a randomized trial published in 1998 showed that in utero repair did not improve survival compared with standard therapy. ^[2]

Subsequent trials of fetal intervention focused on occluding the fetal trachea. The fetal lung secretes fluid by active ion transport through gestation, and this lung fluid provides a template for lung growth. Occlusion of the fetal trachea traps this fluid and stimulates lung growth, either by retention of growth factors within the lung or stimulation of local growth factors by the gentle distension provided by the fluid. Unfortunately, a randomized trial in humans found that fetal tracheal occlusion did not improve outcome compared with standard treatment. ^[3] Currently, fetal intervention is not indicated in congenital diaphragmatic hernia, although some groups continue to offer it on an experimental basis.

Until relatively recently, specialists believed that reduction of the herniated viscera and closure of the diaphragmatic defect should be emergently performed following birth. However, a delayed surgical approach that enables preoperative stabilization decreases morbidity and mortality. This change in protocol was due to the understanding that the medical problems of pulmonary hypoplasia and PPHN are largely responsible for the outcome of congenital diaphragmatic hernia and that the severity of these pathophysiologies is largely predetermined in utero. ^[25] Herniated viscera in the chest does not appear to exacerbate the pathophysiology as long as bowel decompression with a nasogastric tube is adequate.

Severe grade of congenital diaphragmatic hernia appears to be an independent predictor for Nissen fundoplication after congenital diaphragmatic repair. ^[26]

Several reports indicate that circulatory stability, respiratory mechanics, and gas exchange deteriorate after surgical repair. The ideal time to repair a congenital diaphragmatic hernia is unknown. Some suggest that repair 24 hours after stabilization is ideal, but delays of up to 7-10 days are typically well tolerated, and many surgeons now adopt this approach. Some surgeons prefer to operate on these neonates when normal pulmonary artery pressure is maintained for at least 24-48 hours based on echocardiography.

Chest tube drainage is necessary when a tension pneumothorax is present; however, whether routine chest drainage following surgical repair has a role is controversial. Some clinicians report improved survival when chest drainage is not used. Others think that balanced intrathoracic drainage, in which a closed gated pressure system is used to maintain intrathoracic pressure within the normal physiologic range, may minimize risk of pulmonary injury and improve respiratory mechanics.

Transplantation of a single lung has been reported in one case. Lung transplantation may allow the remaining hypoplastic lung to grow and to recover from injury while still allowing adequate oxygenation and ventilation. However, this approach has not been widely used because of the substantial problems associated with donor lung availability and immunosuppression.

Failure to thrive is common, and, in some studies, more than 50% of patients are below the 25th percentile for height and weight during the first year of life. In one study, one third of infants required gastrostomy tube placement to improve caloric intake. The need for supplemental oxygen at the time of discharge is a significant predictor for subsequent growth failure. Possible causes include increased caloric requirements due to chronic lung disease, oral aversion after prolonged intubation, poor oral feeding due to neurologic delays, and gastroesophageal reflux.

Because of the risk for central nervous system (CNS) insult and sensorineural hearing loss, infants should be closely monitored for the first 3 years of life, ^[27]  preferably in a specialty follow-up clinic. These risks are particularly high in infants who are discharged home on supplemental oxygen. Reassess hearing at age 6 months (and later if indicated) because late sensorineural hearing loss occurs in approximately 40% of patients.

Even if a child has no major neurodevelopmental delays, he or she should be evaluated prior to entering school to determine if any subtle deficits may predispose the child to learning disabilities.