Anesthetic Considerations in Congenital Diaphragmatic Hernia

Issues of Concern

Pathophysiology

Neonates with CDH exhibit several critical cardiopulmonary physiological differences, most notably poor gas exchange, left ventricular hypoplasia, right ventricular hypertrophy, and pulmonary hypertension.[1][2] Abdominal viscera compressing the developing lungs interferes with the branching of pulmonary airways and vasculature, leading to pulmonary hypoplasia and vascular remodeling. The underdeveloped lungs are characterized by poor gas exchange, primarily due to thickened alveolar walls and diminished functional surface area, secondary to decreased terminal bronchiolar branching, acinar hypoplasia, and dysfunctional surfactant production.[3] Pulmonary hypertension results from hypertrophy of the pulmonary vasculature and increased vasoreactivity, and is exacerbated by elevated partial pressure of arterial carbon dioxide (PaCO₂) levels and decreased partial pressure of arterial oxygen (PaO₂) levels associated with inefficient gas exchange.[4]

The compressive forces of the herniation can also significantly alter cardiac physiology. Left ventricular hypoplasia with associated poor left ventricular function is common.[5] One likely cause of left ventricular hypoplasia is decreased left ventricular filling pressures due to right-to-left shunting via a patent ductus arteriosus in the setting of pulmonary hypertension. Additionally, compressive forces may cause cardiac rotation, favoring blood flow through a patent foramen ovale (PFO), further exacerbating the shunt, and decreasing left ventricular preload.[6] 

In contrast, the right side of the heart more often shows hypertrophy due to elevated pulmonary pressures and increased PFO shunting, leading to increased afterload and preload, respectively.[7] The combination of significant pulmonary hypertension and residual fetal circulatory elements may lead to severe hypoxemia refractory to conventional treatments, a condition known as persistent pulmonary hypertension of the newborn.[7] Additional physiologic concerns may be identified upon further evaluation with fetal MRI or echocardiography. Notably, intestinal malrotation and congenital heart disease are commonly seen in this patient population; central nervous system, renal, and esophageal abnormalities are rarer but may also occur.[2]

Prenatal Stage and Delivery

The only prenatal invasive intervention is fetal endoluminal tracheal occlusion (FETO). Fetal endoluminal tracheal occlusion is generally performed only on fetuses with severe CDH based on observed-to-expected lung-to-head ratio scoring and the presence of liver herniation.[8] The procedure involves percutaneous placement of a balloon in the fetal trachea to prevent the expulsion of pulmonary fluid. During development, blockage of the normal egression of lung fluid increases transpulmonary pressures, helping the fetal lung expand against the herniated viscera. Fetal endoluminal tracheal occlusion is performed around 27 to 29 weeks and is often removed by 34 weeks through ultrasonography-guided balloon puncture or fetal tracheoscopic takedown and retrieval.[9]

The occlusion may also be taken down at birth using the ex utero intrapartum treatment procedure to provide a bridge to intubation.[10] The occlusion is best removed at least 1 day before birth to allow for the repopulation of type 2 pneumocytes, given that tracheal occlusion has been found to reduce these cell numbers.[11] Fetal endoluminal tracheal occlusion is currently considered experimental, although initial case studies showed increased survival rates.[12] Results from the European Tracheal Occlusion to Accelerate Lung Growth and Fetal Endoscopic Tracheal Occlusion (TOTAL) clinical trials are currently pending.[2][13]

Fetal Endoluminal Tracheal Occlusion Anesthetic Considerations

Maternal anesthesia can be achieved with local, combined spinal-epidural, or general anesthesia, depending on the patient's clinical situation and comfort level.[9] Anesthesia for the fetus involves an ultrasonography-guided intramuscular injection of fentanyl, rocuronium, and atropine to achieve analgesia and paralysis while mitigating fetal bradycardia.[2] Because this procedure involves significant stress on the fetus, fetal heart rate is routinely measured by Doppler ultrasonography before and after the operation. Fetal heart rate should be obtained intraoperatively if any concern for fetal deterioration arises. Maternal mean arterial pressure should be maintained within 20% of baseline to ensure adequate uteroplacental blood flow.

Delivery Day

Delivery is planned for 37 to 39 weeks at a tertiary center with extracorporeal membrane oxygenation (ECMO) capabilities.[14]  Deliveries can be performed by either spontaneous vaginal delivery or cesarean delivery. Neonates are intubated at birth, mechanically ventilated, and their stomachs decompressed via an orogastric or nasogastric tube set to low continuous suction. Neonates continue to receive care in the neonatal intensive care unit, where they are medically optimized before diaphragmatic hernia repair.

Preoperative Medical Optimization and Evaluation

Whereas CDH was previously considered a surgical emergency, the current approach emphasizes stabilization of cardiorespiratory function before surgical intervention.[15] Preoperative evaluation is critical to ensure the patient is adequately optimized for the procedure. Critical medical goals for the neonate in preparation for the surgical procedure include improving lung gas exchange and peripheral oxygen delivery, lowering pulmonary arterial pressures to acceptable levels, correcting acid-base imbalances, and addressing significant comorbidities. Additionally, clinicians should determine the point at which the hernia occurred in gestation, because early herniation is associated with worse pulmonary development and requires greater ventilatory assistance compared with late herniation.[14] Pertinent tests and imaging before the surgical procedure include a complete blood count, metabolic panel, lactate level, coagulation assays, arterial blood gas, chest radiography, echocardiography, and head ultrasonography. The CDH Euro Consortium suggested the following stability indicators before the surgical procedure:

• Normal mean arterial pressure for gestation
• Preductal peripheral oxygen saturation (SpO₂₎ between 85% to 95% on fraction of inspired oxygen (FiO₂₎< 50%
• Lactate level < 3 mmol/L
• Urine output > 1 cc/kg/hr [16]

Another consideration for these patients is whether they require ECMO for increased support. Common indications for ECMO include hypoxemia, hypoxia, or metabolic acidosis that is refractory to medical therapy and ventilator treatment. Extracorporeal membrane oxygenation exclusion criteria are lethal chromosomal abnormalities or severe intracranial hemorrhage.[17] Transitioning to ECMO should be considered if any of the following conditions persist despite medical treatment:

• Preductal SpO₂< 85% or postductal SpO₂< 70%
• PaO_{2 )}< 40 mmHg
• Mixed venous saturation < 60%
• Oxygenation index > 40 for at least 3 hours
• Mixed acidosis with pH < 7.2 with hemodynamic instability
• Requiring peak inspiratory pressure (PIP) > 28 cm H₂O or mean airway pressure > 15 cm H₂O to maintain oxygenation
• Lactate level > 5 mmol/L with a pH < 7.2
• Hypotension refractory to fluids and pressors
• Severe air leak requiring high ventilatory settings [17][18]

Oxygenation Index = Mean Airway Pressure x FiO₂ x 100 ÷ PaO₂

Hernia Repair

Delaying the surgical procedure until the patient is medically optimized has been shown to improve patient outcomes, although the timing of the surgical procedure is debated for patients receiving ECMO. Some centers prefer early repair during ECMO, whereas others delay the surgical procedure until the neonate has been successfully weaned off circulatory support.[2] Diaphragmatic surgical repair following hernia reduction options includes primary closure, synthetic patch repair, or an abdominal wall muscle flap repair.[19] Closures by patch or muscle flap are reserved for significant defects that would require excessive tension for primary closure. The repair is performed either thoracoscopically or by an open approach. Thoracoscopic repairs have survival rates similar to those of open procedures but have been associated with higher PaCO₂ levels and acidosis secondary to CO₂ insufflation.[20]

General Anesthetic Approach

Patients are often intubated in the neonatal intensive care unit before transfer to the operating room; for those who require intubation in the operating room, rapid-sequence intubation with propofol is recommended. Mask ventilation should be avoided due to the risk of gastric insufflation. Neuromuscular blocking agents should generally be avoided for intubation because evidence indicates that their administration leads to deterioration in lung function without any apparent added benefit.[21] An arterial line is essential for intraoperative monitoring and is preferentially placed in the right radial artery to provide preductal measurements. Venous access is best obtained in the upper extremities because reducing herniated viscera increases intra-abdominal pressure, potentially decreasing inferior vena cava flow. Central lines may be helpful because they can be used postoperatively to administer vasoactive medications. For gastric decompression, a nasogastric or orogastric tube should be placed to low continuous suction. Anesthesia is maintained primarily through high-dose intravenous opioids. Volatile anesthetics can be used as supplemental agents. However, these agents should be given cautiously to avoid compromising cardiac output. Nitrous oxide use is avoided, given the risk of expansion within the thoracic cavity or herniated viscera. As with intubation, neuromuscular blocking agents are not recommended because of decreased lung compliance resulting from the loss of spontaneous ventilation.[21]

Intraoperative Monitoring

Monitoring should include preductal and postductal pulse oximetry, an arterial line, and standard monitors for heart rate, noninvasive blood pressure cuff, temperature, end-tidal CO₂, and a 3- or 5-lead electrocardiogram. An increase in the difference between preductal and postductal saturations may indicate worsening pulmonary hypertension, causing an associated expansion of the right-to-left patent ductus arteriosus shunt. The arterial line is needed for invasive blood pressure monitoring and arterial blood gas analysis. Laboratory studies to monitor include hemoglobin and hematocrit levels, glucose levels, and arterial blood gases. Clinicians should also regularly monitor the nonoperative lung field for evidence of pneumothorax, as it may occur secondary to excessive ventilatory pressures.[2]

Ventilation

Ventilation goals are similar to the clinical stability indicators listed previously. Ventilator optimization strives to ensure adequate oxygenation and ventilation while avoiding barotrauma. Clinicians accomplish this goal by using permissive hypercapnia, careful monitoring of PIP, and high-frequency oscillatory ventilation when conventional mechanical ventilation fails. While respiratory alkalosis from hyperventilation would reduce pulmonary hypertension and shunt via the patent ductus arteriosus, this approach carries an increased risk of barotrauma. Excessive ventilatory pressures increase the risk of contralateral pneumothorax.[16][22] General goals for ventilation include the following:

• Preductal SpO₂ of 85% to 95%
• Postductal SpO₂> 70%
• PIP < 25 cm H₂O with a positive end-expiratory pressure set between 3 and 5 cm H2O
• FiO₂< 50%, titrated to preductal SpO₂ goals
• Respiratory rate between 40 and 60 breaths per minute
• PaCO₂ between 50 and 70 mmHg
• the pH of 7.25 or greater [16][22]

Cardiovascular

Hemodynamic goals include maintaining adequate cardiac output and blood pressure with inotropes, vasopressors, and fluids. Target blood pressure ranges should be based on the neonate's gestational age. Most patients with CDH have concomitant adrenal insufficiency based on low random cortisol measurements; hypotension in this population generally responds well to stress-dose hydrocortisone. However, results from studies found that long-term administration of corticosteroids increased the risk of mortality and sepsis.[23][24] Fluid boluses of 10 to 20 mL/kg are also appropriate if the patient is hypovolemic. Dextrose-rich maintenance fluids are given for caloric and hemodynamic requirements but should be monitored carefully to avoid compromising cardiac function. 

Pulmonary Hypertension

Pulmonary hypertension is often prominent in this patient population. Commonly used medications include inhaled nitric oxide and milrinone. Pulmonary vasodilatory therapy should not be used routinely in all patients. Instead, therapy should be reserved for those with signs of poor organ perfusion with preductal SpO2 less than 85% or a difference between preductal and postductal SpO₂ readings greater than 10%.[25] If pulmonary hypertension treatment is required, inhaled nitric oxide can be initiated for patients with normal left ventricular function, whereas milrinone may be more appropriate for neonates with comorbid left ventricular diastolic dysfunction.[1] Milrinone in this setting can additionally act as a lusitrope to increase left ventricular filling and reduce the left-to-right shunt via the patent ductus arteriosus. If no response is seen with these agents, a second-line agent may be administered, such as a prostacyclin or a phosphodiesterase inhibitor.

Postoperative Management

While in the postanesthesia care unit, the patient needs continued hemodynamic monitoring and supportive care. Lung fields should be regularly assessed for any evidence of pneumothorax, hemorrhage, or atelectasis. Postoperative care continues in the neonatal intensive care unit with the patient intubated and mechanically ventilated. Ventilatory and hemodynamic support are weaned when tolerated. A multimodal pain regimen may include opioids, an epidural, and acetaminophen if liver function test results are normal. Clinicians monitor for the return of bowel function and encourage initiating enteral feeding when tolerated to optimize postoperative recovery.

Many factors contribute to the morbidity and survival outcomes of patients with congenital diaphragmatic hernia, including lung hypoplasia, persistent pulmonary hypertension, and cardiac dysfunction. However, the primary determinant of prognosis remains the degree of pulmonary hypoplasia.[26] Pulmonary hypoplasia often leads to airway obstruction and pulmonary hyperinflation. A commonly used predictor of outcome is the observed-to-expected lung-to-head ratio, which correlates well with survival. In patients requiring extracorporeal membrane oxygenation, the mediastinal shift index can be used. Mediastinal shift index is calculated by dividing the distance between the venous cannula tip and the contralateral chest wall by the total width of the contralateral hemithorax.[27] Although the reported prevalence of CDH has increased, the associated mortality rate has decreased since 2015. Nonetheless, in 2022, infants diagnosed with CDH still had a significant mortality rate, ranging from 30% to 60%.[28]

Clinical Significance

Caring for patients with congenital diaphragmatic hernia is both rewarding and often complex. Perioperative treatment of these patients relies heavily on an understanding of the underlying physiology, experimental evidence, and expert consensus. The primary goals for these patients involve identifying the unique anatomic and physiologic changes through perinatal evaluation, enhancing prenatal pulmonary development, stabilizing and medically optimizing neonates after delivery, and safely repairing the diaphragmatic defect under general anesthesia. During the prenatal stage, the anesthesia team can provide maternal and fetal anesthesia to facilitate successful tracheal occlusion in patients undergoing fetal endoluminal tracheal occlusion.

Preoperatively, the team's role is to ensure the neonate is sufficiently stable to tolerate anesthesia and the stress of surgery. For the diaphragmatic repair, the anesthesiologist provides anesthesia and analgesia for the infant while monitoring clinical stability and assessing potential complications. The key intraoperative priorities are to ensure hemodynamic stability, manage pulmonary hypertension as needed, and avoid pulmonary barotrauma through ventilator optimization.

Enhancing Healthcare Team Outcomes

Patients diagnosed with congenital diaphragmatic hernia have complex needs that require the services of multiple hospital teams to provide optimal treatment and support. Perioperative treatment of these patients involves extensive cooperation between interprofessional team members. The anesthesia team coordinates closely with the neonatologist, pediatric surgery, and maternal-fetal medicine teams regarding medical treatment and the timing of procedures. Maintaining open and consistent communication with the surgical and intensive care unit teams is key to ensuring the neonate’s medical condition is fully optimized and maximizing the likelihood of a successful procedure.

Many other professional teams also have important roles in caring for these patients, including intensive care unit nursing staff, respiratory therapists, geneticists, other clinicians, developmental psychologists, social workers, and other allied health professionals. A cohesive interprofessional team can deliver high-quality medical care to these infants and provide comfort and confidence to their parents. Navigating each of the steps from prenatal care through postoperative treatment can be very challenging. During this time, the interprofessional team must provide a unified approach to caring for these infants and communicate that plan clearly to the parents.