Anesthetic Considerations in Congenital Diaphragmatic Hernia

Issues of Concern

Pathophysiology

Neonates with congenital diaphragmatic hernia have several critical differences in cardiopulmonary physiology, most notably poor gas exchange, left ventricular hypoplasia, right ventricular hypertrophy, and pulmonary hypertension.[2][3] 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 caused primarily by thickened alveolar walls and diminished functional surface area secondary to decreased bronchiolar terminal branching, acinar hypoplasia, and dysfunctional surfactant production.[4] Pulmonary hypertension results from hypertrophy of pulmonary vasculature and increased vasoreactivity and is exacerbated by the elevated arterial carbon dioxide (PaCO₂) levels and decreased oxygen (PaO₂) levels associated with inefficient gas exchange.[5]

The compressive forces of the herniation also can alter cardiac physiology significantly. Left ventricular hypoplasia with associated poor left ventricular function is not an uncommon finding.[6] One likely cause of left ventricular hypoplasia is decreased left ventricular filling pressures due to right-to-left shunting via a patent ductus arteriosus (PDA) 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.[7] By contrast, the right side of the heart is more often found to have hypertrophy due to the elevated pulmonary pressures and increased PFO shunting, leading to increases in both afterload and preload, respectively.[8] 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 (PPHN).[8] Additional physiologic concerns may be brought to light upon further evaluation with fetal MRI or echocardiography. Intestinal malrotation and congenital heart disease are commonly seen in this patient population; CNS, renal, and esophageal abnormalities are rarer but may also occur.[3]

Prenatal Stage and Delivery

The only prenatal invasive intervention is fetal endoluminal tracheal occlusion (FETO). It is generally only performed on fetuses with severe CDH based on observed-to-expected lung-to-head ratio (O/E LHR) scoring and the presence of liver herniation.[9] The procedure involves the 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 transpulmonic pressures, helping the fetal lung expand against the herniated viscera. This occlusion is performed around 27 to 29 weeks and is often removed by 34 weeks through ultrasound-guided balloon puncture or fetal tracheoscopic takedown and retrieval.[10]

The occlusion may also be taken down at birth using the ex-utero intrapartum treatment procedure to provide a bridge to intubation.[11] The occlusion is best removed at least 1 day before birth to allow for the repopulation of type II pneumocytes, given that tracheal occlusion has been found to reduce these cell numbers.[12] FETO is currently considered experimental, although initial case studies showed increased survival rates after undergoing FETO.[13] Results from the European Tracheal Occlusion to Accelerate Lung Growth and Fetal Endoscopic Tracheal Occlusion clinical trials are currently pending.[3][14]

FETO Anesthetic Considerations

Maternal anesthesia can be achieved with local, spinal-epidural, or general anesthesia, depending on the patient's clinical situation and comfort level.[10] Anesthesia for the fetus involves an ultrasound-guided intramuscular injection of fentanyl, rocuronium, and atropine to achieve analgesia and paralysis while mitigating fetal bradycardia.[3] As this procedure involves significant stress on the fetus, it is routine to measure fetal heart rate by Doppler ultrasound before and after the operation. It should be obtained intraoperatively if there is any concern for fetal deterioration. Maternal mean arterial pressure (MAP) 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.[15] Deliveries can be performed either as spontaneous vaginal or cesarean sections. Neonates are intubated at birth, ventilated mechanically, and decompressed via an oro- or nasogastric tube set to low continuous suction. Neonates continue to receive care in the neonatal intensive care unit (NICU), which be medically optimized before repairing the diaphragmatic hernia.

Preoperative Medical Optimization and Evaluation

Preoperative evaluation ensures the patient is adequately optimized and stable for the procedure. The critical medical goals for the neonate in preparing for surgery include improving gas exchange in the lungs and oxygen delivery to the periphery, lowering pulmonary arterial pressures to acceptable levels, correcting acid-base imbalances, and addressing significant comorbidities. Additionally, it is essential to ascertain at what point the hernia occurred in gestation, as early herniation is associated with worse pulmonary development and requires greater ventilatory assistance compared to late herniation.[16] Pertinent tests and imaging before surgery include a complete blood count, metabolic panel, lactate, coagulation assays, arterial blood gas, chest X-ray, echocardiography, and a head ultrasound. The CDH Euro Consortium suggested the following as indicators that the neonate is stable for surgery:[15]

• Normal MAP for gestation
• Preductal SpO₂ between 85% to 95% on FiO₂ < 50%
• Lactate < 3 mmol/L
• UOP > 1 cc/kg/hr

Another consideration for these patients is whether or not they require ECMO for increased support. Common indications for ECMO include hypoxemia, hypoxia, or metabolic acidosis that is refractory to medical therapy and ventilator management. ECMO exclusion criteria may consist of lethal chromosomal abnormalities or severe intracranial hemorrhage.[17] Transitioning to ECMO should be considered if any of the following conditions persist refractory to medical treatment:[17][18]

• Preductal SpO₂ < 85% or postductal SpO₂ < 70%
• PaO₂ < 40 mm Hg
• Mixed venous saturation < 60%
• Oxygenation index > 40 for at least 3 hours
• Mixed acidosis pH < 7.2 with hemodynamic instability
• Requiring PIP > 28 cmH₂O or MAwP > 15 cmH₂O to maintain oxygenation
• Lactate > 5 mmol/L with a pH < 7.2
• Hypotension refractory to fluids and pressors
• Severe air leak and requiring high ventilatory settings

*PIP = peak inspiratory pressure; MAwP = mean airway pressure; FiO₂ = fraction of inspired oxygen; oxygenation index = MAwP x FiO₂ x 100 ÷ PaO₂.

Hernia Repair

Delaying surgery until the patient is medically optimized has been shown to improve patients' outcomes, although the timing of surgery is debated for patients on ECMO. Some centers prefer early repair on ECMO, while others delay surgery until the neonate has successfully been weaned off circulatory support.[3] Diaphragmatic surgical repair following hernia reduction options include 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 too much tension for primary closure. The repair is performed either thoracoscopically or open. Thoracoscopic repairs have similar survival rates to open procedures but have been associated with higher levels of PaCO₂ and acidosis secondary to CO₂ insufflation.[20]

General Anesthetic Approach

Patients are often intubated in the NICU 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, given the risk of gastric insufflation. Neuromuscular blocking agents should generally be avoided for intubation as there is evidence of lung function deterioration with administration 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 as the reduction of herniated viscera increases abdominal compartment pressures, potentially decreasing the inferior vena cava flow. Central lines may be helpful as they can be used postoperatively to administer vasoactive medications. For gastric decompression, a naso or orogastric tube should be placed to low continuous suction. Anesthesia is maintained primarily through high-dose intravenous intravenous opioids. Volatile anesthetics can be used as a supplement. 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, given decreased lung compliance from the loss of spontaneous ventilation.[21]

Intraoperative Monitoring

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

Ventilation

Ventilation goals are similar to clinical stability indicators as above. Ventilator optimization strives to ensure adequate oxygenation and ventilation while avoiding barotrauma. This is accomplished by using permissive hypercapnia, careful monitoring of PIP, and high-frequency oscillatory ventilation when CMV fails. While respiratory alkalosis from hyperventilation would decrease pulmonary hypertension and reduce shunting via the PDA, it carries an increased risk of barotrauma. Excessive ventilatory pressures increase the risk of incurring a contralateral pneumothorax.[15][22] General goals for ventilation include the following:

• Preductal SpO₂ between 85% to 95%
• Postductal SpO₂ > 70%
• PIP < 25 cmH₂O with a PEEP set between 3 to 5 cmH2O
• FiO₂ < 50%, titrated to preductal SpO₂ goals
• Respiratory rate between 40 to 60 breaths per minute
• PaCO₂ between 50 to 70 mm Hg
• the pH of 7.25 and above[15][22]

*PEEP = positive end-expiratory pressure

Cardiovascular

Hemodynamic goals are maintaining adequate cardiac output and blood pressure through 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, long-term administration of steroids has been found to increase the risk of mortality and sepsis.[23][24] Fluid boluses of 10 to 20 cc/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 not compromise cardiac function. 

Pulmonary Hypertension

Pulmonary hypertension is often prominent among this patient population. Commonly used medications include inhaled nitric oxide (iNO) and milrinone. Pulmonary vasodilatory therapy should not be started routinely on all patients. Still, it should be somewhat reserved for those with signs of poor organ perfusion with preductal SpO₂ < 85% or a difference between pre and postductal SpO₂ readings more significant than 10%.[25] If requiring pulmonary hypertension treatment, iNO can be initiated for those patients with a normal functioning left ventricular, whereas milrinone may be more appropriate for those neonates with comorbid left ventricular diastolic dysfunction.[2] Milrinone in this setting can additionally act as a lusitrope to increase left ventricular filling and reduce the left-to-right shunt via the PFO. 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 post-anesthesia 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 NICU with the patient intubated and mechanically ventilated. Ventilatory and hemodynamic support is weaned as tolerated. A multimodal pain regimen may include opioids, an epidural, and acetaminophen if liver function tests are normal. They monitor for return of bowel function, and initiating enteral feeding as tolerated is encouraged for optimal postoperative recovery.

Clinical Significance

Caring for patients with congenital diaphragmatic hernia is both rewarding and often complex. The perioperative management of these patients relies significantly on understanding the underlying physiology, experimental evidence, and expert consensus. The primary goals for these patients involve identifying the unique anatomic and physiologic changes through perinatal work-up, enhancing prenatal pulmonary development, stabilizing and optimizing medically 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 enable successful occlusion of the trachea for those patients undergoing FETO. Preoperatively, the role of the team is to ensure the neonate is sufficiently stable to tolerate the anesthesia and 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 focuses are ensuring hemodynamic stability, managing pulmonary hypertension as needed, and avoiding 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. Managing the perioperative care of these patients involves extensive cooperation between interprofessional team members. The anesthesia team coordinates closely with the neonatologist ICU, pediatric surgery, and maternal-fetal medicine team regarding medical management and timing of the procedures. Maintaining open and consistent communication with the surgical and ICU teams is key to ensuring the neonate’s medical condition is fully optimized and maximizes the likelihood of a successful procedure. Many other professional teams also take important roles in caring for these patients, including ICU nursing staff, respiratory therapists, geneticists, other physician specialists, developmental psychologists, social workers, and other allied health professionals. A cohesive interprofessional team can effectively achieve high-quality medical care for these infants and provide a source of comfort and confidence for the parents of the neonates. Navigating each of the steps from prenatal care through postoperative management can be very challenging. During this time, the interprofessional teams must provide a unified approach to caring for these infants and communicate that plan clearly to the parents.