Congenital Diaphragmatic Hernia

Introduction

• CDH is a developmental defect of the diaphragm that leads to the herniation of abdominal organs into the thoracic cavity.¹
  • Normal lung development and function are disrupted by this herniation.
• The prevalence of CDH has been estimated at 2-3 cases per 10,000 live births.²
• CDH is classified by anatomical location into posterolateral, anterior, or central defects.¹
  • The majority of CDH cases (70-75%) occur in the posterolateral (Bochdalek) region and on the left side (85%).^1,3
  • In left-sided herniations, the stomach, intestines, and occasionally the liver are displaced into the chest cavity.³
    • Right-sided CDH is less common and is characterized by the herniation of the liver and intestines into the chest cavity.³
    • Bilateral herniation is rare (less than 2% of cases).³
  • Anterior (Morgagni) and central hernias are less common.^1,3
• CDH commonly leads to pulmonary hypoplasia and pulmonary hypertension in the newborn.
• Most cases of CDH are discovered prenatally by routine antenatal ultrasound screening. CDH may also be detected as a workup for maternal polyhydramnios.^1,2
  • The presence of abdominal viscera within the chest cavity is considered a characteristic finding suggestive of CDH.¹
  • Indirect findings of CDH may include polyhydramnios, mediastinal shift, or an abnormal cardiac axis.¹
• Further evaluation of CDH is performed by using a detailed fetal anatomic survey, fetal magnetic resonance imaging, fetal echocardiogram, and genetic testing/counseling.³
• After birth, cyanosis and dyspnea are typically observed within the first few minutes.²
  • Physical examination findings include a scaphoid abdomen, a barrel-shaped chest, absent breath sounds on the ipsilateral side, and bowel gas patterns in the chest with mediastinal shift.²
  • The heartbeat in patients with a left-sided CDH is often displaced to the right due to mediastinal shift.²
• Advances in prenatal imaging have led to earlier detection and identification of prognostic factors.
  • Poor prognostic factors include the following:¹
    • An observed-to-expected lung-to-head circumference ratio below 25%
    • Herniation of the liver into the thoracic cavity
    • Percent predicted lung volume of less than 15%
    • Total lung volume under 20 mL
    • Right-sided CDH
    • Hypoplasia of the left ventricle
    • Concurrent cardiac and chromosomal anomalies

Etiology

• The etiology of CDH is not fully understood, but it is thought to be multifactorial with genetic and environmental factors.
• Approximately 50-70% of CDH cases are observed as isolated anomalies and are not associated with genetic syndromes.¹
• Nonisolated CDH cases have been associated with other congenital anomalies in approximately 30-50% of cases.1
  • Cardiovascular malformations reported in CDH include ventricular septal defects, atrial septal defects, Tetralogy of Fallot, aortic coarctation, and vascular rings.^1,2
  • Nervous system malformations reported include hydrocephalus and neural tube defects.^1,2
  • Limb malformations, such as polydactyly and limb reduction defects, have also been associated with nonisolated CDH cases.¹
• The identification of copy-number variants, chromosomal abnormalities, and single-gene mutations has been linked to the development of CDH.¹
  • Trisomy 18 has been reported as the most prevalent aneuploidy associated with CDH.¹
  • Trisomy 13 and trisomy 21 have also been linked with CDH.¹
• Several syndromes have known associations with CDH.
  • These syndromes include Fryns Syndrome, Donnai-Barrow Syndrome, Pallister-Killian Syndrome, Cornelia de Lange Syndrome, Wolf-Hirschhorn Syndrome, CHARGE Syndrome, etc.^1,2
• Environmental factors have also been implicated in the development of CDH.
  • Reported environmental factors include maternal vitamin A deficiency, alcohol consumption, and tobacco exposure.¹
  • The etiology of CDH is hypothesized to involve disruptions in the retinoid-signaling pathway, which was first proposed by Greer et al.¹

Pathophysiology

• The herniation of abdominal viscera into the thoracic cavity disrupts normal lung development.
  • Contralateral lung development is further impaired as a result of the mediastinal shift in CDH.²
• Histopathological findings in the lungs include reduced terminal bronchiolar branching, thickened alveolar walls, and increased interstitial tissue, resulting in decreased surface area for gas exchange.^1,2
• Pulmonary hypertension in CDH is characterized by pulmonary vascular hypertrophy and increased vasoreactivity.^1,2
• The pulmonary hypertension in CDH has both “reversible” and “fixed” components.
  • The “reversible” component of persistent pulmonary hypertension of the newborn (PPHN) in CDH is primarily driven by altered vasoreactivity. Underlying mechanisms include endothelial dysfunction, impaired nitric oxide signaling, and an imbalance between vasoactive mediators.¹
  • The “fixed” component of PPHN in CDH refers to the irreversible pulmonary vasculature remodeling, including medial and adventitial thickening and decreased pulmonary vascular cross-sectional area.¹
• Left ventricular hypoplasia may also be observed in infants with severe left-sided CDH.¹ The underlying pathophysiology is multifactorial, involving mechanical compression of the left heart by herniated abdominal viscera and altered fetal hemodynamics.
  • Left-sided CDH is associated with altered fetal hemodynamics that disrupt normal fetal circulation, leading to preferential streaming of blood towards the right heart and away from the foramen ovale, contributing to left ventricular hypoplasia.¹

Delivery Room Management

• The delivery of infants with prenatally diagnosed CDH is typically planned after 39 weeks’ gestation at a high-volume tertiary care center.¹
• Immediate endotracheal intubation at birth is recommended for all infants with prenatally diagnosed CDH.^5,6
  • Bag-mask ventilation should be avoided as it can cause gastric and bowel distention, thereby worsening lung compression.^5,6
  • The administration of neuromuscular blocking agents for intubation has been shown to cause deterioration in lung function and, therefore, is not recommended.⁵
• After intubation, an orogastric or nasogastric tube should be placed under low continuous suction to decompress the stomach and reduce respiratory and cardiovascular compromise.^5,6
• Lung-protective ventilation strategies, including gentle ventilation with permissive hypercapnia, are recommended to optimize gas exchange while avoiding ventilator-induced lung injury.
• Monitoring should include preductal and postductal pulse oximetry and an arterial line.^1,5
• Once the infant is clinically stable, they should be transferred to the neonatal intensive care unit (NICU).

Preoperative Evaluation

• A thorough preoperative evaluation is essential for patients with CDH, given their high risk for respiratory and cardiovascular complications.
• Recommended laboratory tests include arterial blood gas, complete blood count, basic metabolic panel, serum lactate, and coagulation profile.⁵
• An echocardiogram is obtained to evaluate for associated cardiovascular anomalies, ventricular function, and to assess the degree of pulmonary hypertension.²

Ventilation Strategies

• Ventilation in patients with CDH is aimed at optimizing oxygenation and minimizing ventilator-induced lung injury, primarily by implementing “gentle ventilation” with permissive hypercapnia.^1,5
  • Target ranges for permissive hypercapnia include PaCO₂ between 50 to 70 mmHg with pH ≥7.25.⁵
• Conventional mechanical ventilation (CMV) is considered the preferred initial ventilation modality for patients with CDH.¹
  • Ventilation goals include preductal oxygen saturation between 80 and 95%, postductal oxygen saturation greater than 70%, and a target PaCO₂ of 50-70 mmHg.¹
  • Recommended initial CMV settings include the following:¹
    • A positive end-expiratory pressure of 3-5 cm H₂O
    • A peak inspiratory pressure below 25 cm H₂O
    • Respiratory rate of 40-60 breaths/minute, with adjustments made to maintain target PaCO₂ levels
• High-frequency oscillatory ventilation may be used for severe cases or as a rescue therapy when CMV fails to maintain adequate gas exchange.^1,5

Management of Pulmonary Hypertension

• Pulmonary hypertension is frequently observed as a complication in patients with CDH.
• Management of pulmonary hypertension is guided by disease severity and is often achieved through the administration of inhaled nitric oxide, milrinone, prostacyclin/phosphodiesterase inhibitors/endothelin receptor antagonists, and extracorporeal membrane oxygenation (ECMO) for severe cases.¹
  • The administration of inhaled nitric oxide, a selective pulmonary vasodilator, has been shown to provide short-term improvements in oxygenation.⁷
    • Patients with CDH who exhibit right-to-left atrial shunting may respond more favorably to inhaled nitric oxide.¹
  • Milrinone is typically used for patients with left ventricular diastolic dysfunction to enhance cardiac output.⁵
  • Prostacyclin analogues, phosphodiesterase inhibitors, and endothelin receptor antagonists may be employed for refractory or persistent pulmonary hypertension.⁶

ECMO

• ECMO may be considered for patients with CDH who experience respiratory and circulatory failure despite maximal conventional therapy.
  • Veno-arterial ECMO is the most common cannulation method used for CDH.⁶
• Common indications for ECMO in patients with CDH include the following:¹
  • Refractory hypotension due to impaired left ventricular function
  • Mixed acidosis with pH <7.2
  • Persistent preductal oxygen saturation below 80% despite maximal support
  • An oxygenation index >40 for at least three hours
  • Severe air leak
• The use of ECMO is contraindicated in the following scenarios:⁶
  • Grade III/IV intracranial hemorrhage
  • The presence of life-limiting anomalies
  • Unrepairable severe cardiac defects
  • Marked prematurity (typically gestation age <34 weeks)
  • Low birth weight (birth weight <2 kg)

Hemodynamic Monitoring

• A mean arterial pressure (MAP) of 45-55 mmHg is generally recommended in the hemodynamic monitoring of patients with CDH.⁶
  • This target is recommended to reduce right-to-left shunting and maintain adequate systemic perfusion.⁶
• When hypovolemia is suspected and left ventricular function is preserved, administration of 10–20 mL/kg of isotonic crystalloids is recommended.¹
  • Vasopressor therapy may be warranted in cases where patients are fluid-unresponsive.¹
• Adrenal insufficiency is often observed in patients with CDH. Stress-dose hydrocortisone is typically administered to restore hemodynamic stability.¹
• Catecholamine-resistant shock is also often seen in patients with CDH and typically responds to the administration of vasopressin.¹

Surgical Repair

• CDH is not considered a surgical emergency after birth.⁸ Surgery during the “honeymoon” period (12-36 hours after birth) is associated with poor outcomes.¹ Surgical repair is recommended after optimization of pulmonary and systemic hemodynamics, gas exchange, and management of pulmonary hypertension.
• According to the CDH Euro Consortium, the following parameters should be met before undergoing surgical repair:⁵
  • Normal MAP for gestation
  • Lactate less than 3 mmol/L
  • Urine output more than 1 cc/kg/hour
  • Preductal SpO₂ between 85-95% on FiO₂ below 0.5
• Most centers wait for echocardiogram-estimated pulmonary artery pressures to fall below 80% of systemic pressure before proceeding with surgical repair.¹
• For patients on ECMO, surgical repair is usually delayed until decannulation for infants who can be weaned off ECMO. For patients who are unable to be weaned off ECMO, early surgical repair within 48-72 hours of cannulation is recommended.¹
• Surgical repair involves a subcostal incision, pulling the abdominal contents back into the abdominal cavity, and closing the defect.^6,8
• Surgery can be open or minimally invasive.^6,8
  • Open surgical repair is performed for larger defects.^6,8
  • The thoracoscopic approach is typically reserved for patients with smaller defects. This approach has been shown to reduce ventilation time, postoperative pain, and overall hospital stay, and to promote faster recovery.⁸
• Primary closure, which involves directly suturing the defect, is recommended for smaller defects. Patch closure is typically reserved for larger defects.^6,8

Anesthetic Considerations

• Stable patients may be transported to the operating room for surgical repair. However, most patients are repaired at the bedside in the NICU.
• Intraoperative monitoring should include standard American Society of Anesthesiologists monitors, preductal and postductal pulse oximetry, and an arterial line.⁵
  • Preductal and postductal pulse oximetry are used to detect differences in oxygen saturation between the upper and lower extremities.⁵
  • Invasive blood pressure monitoring is recommended for close intraoperative monitoring and arterial blood gas analysis.⁵
  • It is recommended to place the arterial line in the right radial artery to obtain preductal measurements.⁵
• Lung-protective ventilation strategies should be continued, as previously described.
  • Aggressive positive-pressure ventilation during or after surgical repair may precipitate a contralateral pneumothorax.
• The anesthetic approach is typically a high-dose opioid (e.g., fentanyl) and muscle relaxant.¹
• The use of nitrous oxide should be avoided in patients with CDH.⁵
  • Nitrous oxide rapidly diffuses into gas-filled spaces, such as the herniated stomach and bowel seen in CDH.⁵
  • Consequently, nitrous oxide can exacerbate the expansion of herniated viscera, thereby increasing intrathoracic pressure and worsening respiratory compromise.⁵
• Paying close attention to the patient’s hemodynamics and ventilation is critical.
• After surgical repair, patients remain intubated and are transported back to the NICU.