Issues of Concern
Neonates with CDH have several key differences in cardiopulmonary physiology, most notably being poor gas exchange, left ventricular (LV) hypoplasia, right ventricular (RV) hypertrophy, and pulmonary HTN (PH). Abdominal viscera compressing the developing lungs interferes with branching of pulmonary airways and pulmonary 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.
PH results from hypertrophy of pulmonary vasculature as well as increased vasoreactivity and is exacerbated by the elevated arterial carbon dioxide (PaCO2) levels and decreased oxygen (PaO2) levels associated with inefficient gas exchange.
The compressive forces of the herniation also have the potential to alter cardiac physiology significantly. LV hypoplasia with associated poor LV function is not an uncommon finding. One likely cause of LV hypoplasia is decreased LV 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 LV preload. By contrast, the right side of the heart more often is found to hypertrophy due to the elevated pulmonary pressures and increased PFO shunting, leading to increases in both afterload and preload, respectively. The combination of significant PH 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).
Additional physiologic concerns may be brought to light upon further evaluation with fetal MRI or echocardiography. Intestinal malrotation and congenital heart disease are both commonly seen in this patient population; CNS, renal, and esophageal abnormalities are rarer but may also occur.
Prenatal Stage and Delivery
Currently, the only prenatal invasive intervention offered is fetal endoluminal tracheal occlusion (FETO) and 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. The procedure involves the percutaneous placement of a balloon in the fetal trachea to prevent expulsion of pulmonary fluid. Blockage of the normal egression of lung fluid during development will increase 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 either through ultrasound-guided puncture of the balloon or fetal tracheoscopic takedown and retrieval.
The occlusion may also be taken down at birth, making use of the ex-utero intrapartum treatment (EXIT) procedure to provide a bridge to intubation. The occlusion is best removed at least one day prior to birth to allow for repopulation of type II pneumocytes, given that tracheal occlusion has been found to reduce these cell numbers. FETO is currently considered experimental, although initial case studies showed increased survival rates after undergoing FETO. Results from the European Tracheal Occlusion to Accelerate Lung Growth (TOTAL) and Fetal Endoscopic Tracheal Occlusion (FETO) clinical trials are currently pending.
FETO Anesthetic Considerations
Maternal anesthesia can be achieved either with local, spinal-epidural, or general anesthesia, depending on the clinical situation and comfort level of the patient. Anesthesia for the fetus involves an ultrasound-guided intramuscular injection of fentanyl, rocuronium, and atropine to achieve analgesia and paralysis while mitigating fetal bradycardia. As this procedure will involve significant stress to the fetus, it is routine to measure fetal heart rate by Doppler ultrasound both before and after the operation and 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 is planned for 37 to 39 weeks at a tertiary center with extracorporeal membrane oxygenation (ECMO) capabilities. Deliveries can be performed either as spontaneous vaginal or cesarean section. Neonates are intubated at birth, ventilated mechanically, and decompressed via an oro- or nasogastric tube set to low continuous suction. Neonates will continue to receive care in the neonatal intensive care unit (NICU), where they will 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 key 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 any significant comorbidities. Additionally, it is important to ascertain at what point the hernia occurred in gestation, as early herniation is associated with worse pulmonary development and requires greater ventilatory assistance when compared to late herniation.
Pertinent tests and imaging to be performed prior to surgery include a complete blood count, complete 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:
- Normal MAP for gestation
- Preductal SpO2 between 85% to 95% on FiO2 < 50%
- Lactate < 3 mmol/L
- UOP > 1 cc/kg/hr
An additional 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 include lethal chromosomal abnormalities or severe intracranial hemorrhage. Transitioning to ECMO should be considered if any of the following conditions persist refractory to medical treatment:
- 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.
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.
Options for diaphragmatic surgical repair following hernia reduction include primary closure, synthetic patch repair, or an abdominal wall muscle flap repair. Closures by patch or muscle flap are reserved for large 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.
General Anesthetic Approach
Patients are often intubated while in the NICU prior to transfer to the operating room (OR); for those who require intubation in the OR, it is recommended to do rapid-sequence intubation with propofol. Mask ventilation should be avoided, given the risk of gastric insufflation. Neuromuscular blocking agents (NMBAs) should generally be avoided for intubation as there is evidence of lung function deterioration with administration without any apparent added benefit.
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 will increase abdominal compartment pressures, potentially decreasing the flow of the inferior vena cava. Central lines may be helpful as they can be used postoperatively to administer vasoactive medications. A naso or orogastric tube should be in place and set to low continuous suction for gastric decompression.
Anesthesia is maintained primarily through high-dose intravenous (IV) 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, NMBAs are not recommended given decreased lung compliance from the loss of spontaneous ventilation.
Monitoring should include pre and postductal pulse oximetry, an arterial line, and the standard monitors for heart rate, noninvasive blood pressure (BP) cuff, temperature, end-tidal CO2, and a three- or five-lead EKG. An increase in the difference between pre and postductal saturations may indicate worsening pulmonary hypertension, causing an associated increase of the right-to-left PDA shunt. The arterial line is needed for invasive BP monitoring and arterial blood gas analysis (ABG). Labs to monitor include hemoglobin/hematocrit, glucose, and ABGs. It is also important to regularly monitor the nonoperative lung field for evidence of pneumothorax as this may occur secondary to excessive ventilatory pressures.
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. 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
*PEEP = positive end-expiratory pressure
Hemodynamic goals are to maintain adequate cardiac output and blood pressure through the use of 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. 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 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 but rather reserved for those with signs of poor organ perfusion with preductal SpO2 < 85% or a difference between pre and postductal SpO2 readings greater than 10%.
If requiring PH treatment, iNO can be initiated for those patients with a normal functioning LV, whereas milrinone may be more appropriate for those neonates with comorbid LV diastolic dysfunction. Milrinone in this setting can additionally act as a lusitrope to increase LV filling and reduce the left-to-right shunt via the PFO. If no response is seen with these agents, then a second-line agent may be administered instead, such as a prostacyclin or a phosphodiesterase inhibitor.
While in the post-anesthesia care unit, the patient will need continued hemodynamic monitoring and supportive care. Lung fields should be regularly assessed for any evidence of pneumothorax, hemorrhage, or atelectasis. Postoperative care will continue 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. Monitoring for return of bowel function and initiating enteral feeding as tolerated is encouraged for optimal postoperative recovery.
Caring for patients with CDH is both rewarding and oftentimes complex. The perioperative management of these patients relies significantly on understanding the underlying physiology, experimental evidence, and expert consensus.
The major 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 PH as needed, and avoiding pulmonary barotrauma through ventilator optimization.
Enhancing Healthcare Team Outcomes
Patients diagnosed with CDH 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 the interprofessional team members. The anesthesia team coordinates closely with the neonatologist ICU team, pediatric surgery team, 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 the likelihood of a successful procedure is maximized. 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 towards caring for these infants and communicate that plan clearly to the parents.