Introduction

The diaphragm begins to form at four weeks gestation and is completely formed by the eighth to tenth week. The diaphragm is made up of four embryonic structures: the septum transversum, dorsal esophageal mesentery, the pleuroperitoneal membrane, and muscular ingrowth from the body wall [1]. When these components do not develop properly a defect occurs which permits the abdominal contents to enter the thorax, causing a congenital diaphragmatic hernia (CDH). The most common location of a defect is posterolateral through the foramen of Bochdalek, and occurs more frequently on the left side. Defects in an anterior parasternal location through the foramen of Morgagni and at the esophageal hiatus are less common [2]. The diaphragmatic defect allows abdominal contents to herniate into the thorax, compressing the developing lung. This compression results in irreversible pulmonary hypoplasia on the side of the defect. If the defect is so large that bowel contents shift the mediastinum toward the contralateral side, lung compression and hypoplasia can also occur on the contralateral side. Compression from the bowel has deleterious effects on the pulmonary vasculature as well. Pulmonary arterial remodeling may occur and can lead to persistent pulmonary hypertension, a major cause of morbidity and mortality in patients with a CDH.

Epidemiology

The incidence of CDH is 1 in 2500–3000 live births [3]. Approximately 40 percent of patients with a CDH have concurrent congenital anomalies including congenital heart disease, neural tube defects, and chromosomal abnormalities [4]. Pregestational diabetes and maternal alcohol use may be associated with CDH occurrence [5]. There is significant morbidity and mortality associated with CDH [6]. Survival rates for patients with CDH range from 60 to 90 percent [7]. Current ongoing research suggests that retinoid-regulated genes may play a role in the development of CDH [8].

Diagnosis and Clinical Presentation

The diagnosis of CDH is often made through routine prenatal ultrasonography. Once the diagnosis is made, further imaging can help diagnose other congenital abnormalities, delineate the contents of the hernia, and approximate the severity. Either ultrasound or MRI can aid in determining the ratio of lung area to head circumference, known as the lung-to-head-ratio. MRI can further be used to measure fetal lung volume (FLV). Both of these tests can grade the severity of the hernia and are beneficial in determining prognosis [9].

A neonate with a CDH typically presents with severe respiratory distress at birth, although smaller defects with less hypoplastic lung tissue can present with gradual onset of symptoms during the first days to weeks of life. On physical exam, the patient may have a scaphoid abdomen due to the abdominal contents residing in the chest. Breath sounds are often diminished or absent on the side of the hernia. A left-sided hernia may displace the heart to the right, with heart sounds best auscultated on the right chest. A chest radiograph will show bowel contents in the chest and subsequent decreased lung aeration on the affected side. It may also reveal the aberrant course of a nasogastric or orogastric tube, if present. In large defects, particularly on the right, the liver may also herniate into the chest.

Preoperative Care and Management

Initial management of a neonate with CDH focuses on respiratory symptoms. An endotracheal tube is placed to support oxygenation and ventilation while an orogastric tube is passed to decompress the stomach and intestines. Bag-mask ventilation should be avoided, as distention of the abdominal contents in the chest can impair already compromised oxygenation and ventilation. Distention of the thoracic abdominal contents can also decrease cardiac preload and compress the heart, causing hemodynamic instability. Furthermore, bag-mask ventilation can cause barotrauma to the hypoplastic and noncompliant lungs.

A CDH was once treated as a surgical emergency and carried a very high mortality rate. Patients are now medically managed prior to undergoing repair. Both cardiac and pulmonary functions are optimized prior to proceeding to the operating room. Lung protective ventilation with low inspiratory pressures, low tidal volumes, adequate positive end-expiratory pressure (PEEP), and permissive hypercapnia protects the hypoplastic lung from barotrauma. Surfactant is only useful in preterm neonates with surfactant deficiency [10]. High-frequency oscillatory ventilation (HFOV) may be necessary to ensure adequate oxygenation and ventilation while preventing barotrauma. Cardiac management focuses on prevention and treatment of pulmonary hypertension. Narcotics are used to blunt sympathetic stimulation while ventilation strategies limit hypoxia and severe hypercarbia. Inhaled nitric oxide (iNO), a selective pulmonary vasodilator, can be used in cases of refractory pulmonary hypertension. Inotropic support is often needed to maintain ventricular function and systemic perfusion. Arterial access is necessary for both hemodynamic monitoring and frequent blood gas sampling. An echocardiogram is necessary to measure ventricular function and pulmonary artery pressure while diagnosing any other congenital cardiac anomalies.

A neonate not stabilized on the above-mentioned therapies may require extracorporeal membrane oxygenation (ECMO) support. A head ultrasound is included in the diagnostic workup as intracranial hemorrhage is a contraindication to extracorporeal membrane oxygenation (ECMO) support.

Extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation is an important therapy in the management of a subset of patients with CDH. Neonates known to have very low estimated lung volumes, those failing escalation of respiratory and hemodynamic support, and those who acutely decompensate may require ECMO support.

Many medical centers have specific inclusion and exclusion criteria for placing critically ill neonates on ECMO support. Respiratory indications for ECMO support include a high oxygen index (OI) (OI = MAP × FiO₂ × 100 / PaO₂), high peak inspiratory pressures, and refractory hypercarbia. Cardiac indications include a rising or persistently elevated lactate, long-term need for high-dose inotropic support, low mixed venous oxygen saturation, persistent arrhythmias, and severe cardiac dysfunction. Contraindications to ECMO include conditions in which systemic anticoagulation must be avoided, such as intracerebral hemorrhage, irreversible cardiac or respiratory failure where transplant or ventricular assist device (VAD) is not possible, extreme prematurity, and other significant comorbid conditions with a poor prognosis [11,12]. Extracorporeal membrane oxygenation can be achieved with either two venous cannulas (veno-venous) or with one arterial and one venous cannula (veno-arterial). Veno-venous ECMO only supports gas exchange while veno-arterial ECMO supports both gas exchange and systemic perfusion. Veno-arterial ECMO is often used in patients with CDH to support both ventricular dysfunction due to pulmonary hypertension and oxygen exchange due to hypoplastic lungs. In a neonate on ECMO, the surgical repair of the CDH is often completed while the patient is supported by ECMO.

Operative Repair of CDH

A primary repair, in which the native diaphragm is approximated and sewn together, is done when the defect in the diaphragm is small. The majority of large defects are repaired via an open subcostal abdominal approach. Some centers do minimally invasive laparoscopic CDH repairs through either a thoracoscopic or abdominal approach [13]. Minimally invasive repair is associated with a higher recurrence rate [14]. Large defects often require a patch of synthetic material to close the defect, as the existing diaphragm segments are unable to be approximated. Synthetic patch closure is associated with higher rates of hernia recurrence compared to primary closure [15]. In patients with good pulmonary function and small defects, a minimally invasive thoracoscopic technique can be used for primary repair. Thoracic insufflation may be poorly tolerated with this technique [14].

Although not currently a standard therapy nor shown to improve mortality, fetal interventions exist to modulate the degree of lung hypoplasia [16]. Fetal endoluminal tracheal occlusion (FETO) may be done in cases of very low lung to head ratio that carry a very poor prognosis. In this procedure a fetoscope is inserted percutaneously through the uterus into the trachea of the fetus, and a balloon is deployed. The balloon causes the amniotic fluid in the lungs to buildup pressure and distend the airways, encouraging alveolar growth. The balloon must be removed prior to or at birth, as it would prevent adequate oxygenation after delivery [17].

Anesthetic Management of CDH

Preoperative evaluation of a neonate prior to repair of a CDH should include assessment of current hemodynamic status and echographic assessment of ventricular function and pulmonary artery pressure. Review of current medications and inotropic infusions is imperative. It is important to evaluate if the patient is a candidate for ECMO and have the ECMO team on standby should intraoperative deterioration occur.

Lung protective ventilation strategies used in the ICU and described previously should be continued in the perioperative period. Intraoperative monitoring should include invasive blood pressure monitoring and pre- and postductal oxygen saturation measurement. Venous access should be sufficient for large-volume resuscitation and transfusion, as well as inotrope infusion. Central venous access may be helpful in this regard. Temperature must be meticulously controlled with forced-air warmers, fluid warmers, heating lamps, and elevated operating room temperature. Hypothermia can exacerbate pulmonary hypertension, worsen coagulopathy, and lead to poor enzymatic function. Normal intravascular fluid volume should be targeted. Blood product transfusion is common. Frequent arterial blood gas measurements will help guide intraoperative management to maintain acid–base balance. It is helpful to have iNO readily available should the patient decompensate.

Anesthesia can be maintained with muscle relaxants, narcotics, and potent inhalational agents. Nitrous oxide is avoided as it can distend bowel in both the abdomen and chest. Furthermore, it limits the ability to use a high inspired oxygen concentration. Oxygenation and ventilation are strictly monitored during closure of the abdomen, as patients are at risk of developing abdominal compartment syndrome. Elevated peak inspiratory pressures may be the first sign of abdominal tension that may require a staged closure of the abdomen. Controlled mechanical ventilation is usually continued postoperatively as impaired lung function is not corrected with the CDH repair.

In patients on ECMO, a narcotic-based anesthetic is often performed with use of muscle relaxants. Temperature can be carefully regulated by the ECMO machine. Medications, fluid, and blood products can be administered through the ECMO circuit or intravenously. The ECMO circuit increases the volume of distribution of drugs while the synthetic material of the circuit can absorb medications, making the dosing of lipophilic drugs, such as midazolam and fentanyl, unpredictable [17].

Neuraxial or regional analgesia is a reasonable option in very select patients with excellent pulmonary function and minimal comorbidities in order to facilitate early extubation. Thoracic epidural or paravertebral catheters can provide postoperative analgesia. Prior to placement of any neuraxial catheter, coagulation studies should be performed to evaluate for coagulopathy. In patients who will require multiple days of postoperative mechanical ventilation the risks of neuraxial catheter placement may outweigh the benefit. Extracorporeal membrane oxygenation is a contraindication to neuraxial anesthesia owing to the systemic anticoagulation required.

Outcomes

Factors associated with poor long-term prognosis and decreased survival to discharge include prenatal diagnosis, prematurity, patch repair, need for ECMO, low birth weight, liver herniation, and major postoperative complication such as infection or abdominal compartment syndrome. Patients with coexisting complex congenital heart disease and/or a genetic syndrome have a worse prognosis [18].

Patients that survive into childhood often develop chronic conditions that require long-term follow-up. The most common comorbidities seen in these patients with repaired CDH include chronic lung disease, persistent pulmonary hypertension, recurrent CDH, synthetic patch infection or failure, developmental delay, feeding difficulties, and gastroesophageal reflux [19]. Many of these patients require multiple general anesthetics over their lifetime and careful preoperative assessment should be performed in all children and adults with a history of CDH repair.