Ex utero Intrapartum Treatment (EXIT) Procedure

Anatomy and Physiology

Maternal Anatomy

Multiple anatomical layers must be traversed for the surgeon to gain access to the uterus.[8] The skin and subcutaneous tissues give way to reveal the vertically oriented rectus abdominus muscle fibers, which are joined by an avascular aponeurosis in the midline. Next is the parietal peritoneum, which directly overlies the gravid uterus. Adhesions involving the peritoneum, omentum, bowel, bladder, and other intraperitoneal structures are present in patients who have undergone previous surgeries, especially cesarean delivery.

The uterus is a muscular organ comprising 3 layers: the serosa or perimetrium, the myometrium, and the endometrium, from superficial to deep, respectively.[9] The uterine arteries and veins, stemming from the internal iliac vasculature, run along the lateral surfaces of the uterus and anastomose with the ovarian vessels that stem from the abdominal aorta. These vessels may be at high risk of injury during an EXIT procedure performed for fetal mass due to anatomical distortion secondary to the mass and the need for extended hysterotomy. Injury to these vessels poses a significant threat to the completion of the procedure, as the flow through them is increased 8-fold during pregnancy.[10] The uterine artery lies just superficial to the descending ureter, another relationship that is a source of potential complication during this surgery, though not as emergent as iatrogenic hemorrhage.

The placenta is located within the endometrial cavity, the site of all nutrient and gas exchange between fetus and mother. Most commonly, the placenta is found implanted on the superior wall of the endometrial cavity, also known as fundal implantation.[11] The placenta implants on the anterior wall approximately 25% of the time and, therefore, could be threatened by hysterotomy. Placental location is critical to note in the setting of EXIT, as preservation of the placenta and, thus, fetal circulation is an absolute requirement for success. The amniotic sac is encountered after the hysterotomy is complete; the division of this structure removes the last barrier to fetal delivery.

Fetal Anatomy

Following the axiom, "children are not small adults," the fetal and neonatal airways require distinct knowledge and skills to manage successfully. The neonatal head is approximately 2 times larger in proportion to the body than an adult, resulting in neck flexion and, therefore, airway compromise when fully supine.[12] Conversely, overextension of the neck with a large shoulder roll or other such positioning can narrow the airway as the soft tissue stretch compresses the soft tracheal and laryngeal cartilages.

The entire larynx is tilted anteriorly, and the tongue base is relatively larger, leading to more severe obstruction by tongue relaxation posteriorly. The airway is also more funnel-shaped than an adult airway, with the narrowest portion being the circular or near-circular cricoid cartilage.[13] Some debate exists over whether neonatal cricoid cartilage is more often elliptical or circular.[14][15] A neonate with a large cervical or intrathoracic mass can significantly alter the narrowest airway site. The entire laryngeal structure is also higher in the neck than in the adult, with the glottis lying approximately at the third cervical vertebrae rather than the fourth or fifth.

The laryngeal cartilages are also shaped and angled differently than an adult's. The epiglottis is proportionately longer, more curled into a "U" or omega (Ω) shape, and angled posteriorly over the glottis. The arytenoid, corniculate, and cuneiform cartilages are proportionately larger, and the aryepiglottic folds are nearer to the midline. The cartilages are also more pliable and, thus, more susceptible to external compression.[16] Should endotracheal intubation be pursued, the tube size selection is generally based on weight. Cuffless tubes are used even during positive pressure ventilation due to the funneling of the neonatal airway, with the narrowest point at the cricoid.

Indications

The EXIT procedure was first described in 1997 as a second stage after fetoscopic tracheal clipping or balloon occlusion was performed to treat severe congenital diaphragmatic hernia.[17] As techniques have advanced, so has the list of indications. Chronologically, the procedure has been performed for securing the airway in congenital neck masses with or without mass resection at the time of EXIT, congenital high airway obstruction syndrome (CHAOS), establishment of extracorporeal membrane oxygenation (ECMO) cannulas, and emergency separation of conjoined twins.[4][18][19][20][21][22]

Airway Obstruction

Congenital neck masses that may cause airway obstruction, necessitating treatment include:

• Neck masses
• Congenital high airway obstruction syndrome 
• Airway atresia or stenosis
• Micrognathia
• Removal of tracheal clip or balloon [4][22]

Mass Resection

Fetal masses in which resection is performed to relieve obstruction include:

• Neck masses
• Intrathoracic mass or malformations
• Sacrococcygeal teratomas [4]

Extracorporeal Membrane Oxygenation Cannula Placement

Conditions that have required cannula placement for ECHO include severe congenital heart diseases and diaphragmatic hernias.[4][22]

Separation of Conjoined Twins

Radiographic evaluation to assess the need for a complete EXIT procedure in patients with neck masses has been attempted, as some patients can be delivered vaginally and supported noninvasively or with standard intubation via direct laryngoscopy. The tracheoesophageal displacement index (TEDI) was proposed as a predictive radiological measure that could predict the degree of airway complication and, therefore, the need for EXIT.[23] TEDI is defined as the sum in millimeters of the lateral and ventral displacement of the tracheoesophageal complex from the ventral aspect of the cervical spine as measured on axial magnetic resonance imaging (MRI). The eponymous study found that a TEDI of >12 mm correlated with a complicated airway, as did teratoma pathology, polyhydramnios, and the largest diameter of the mass being 12 mm or more. More extensive retrospective studies and systematic reviews have validated these factors as reliable indicators for EXIT, expanding them to include solid tumors in general and an absent stomach bubble.[7]

Contraindications

As an extension of the work exploring radiographic indications, scenarios less likely to need EXIT have also surfaced. A systematic review found that lymphatic malformations, neck masses <3.5 cm, and any size fetal neck masses without anatomic compression or airway displacement are unlikely to present complications needing more than standard intubation after delivery. Therefore, these are relative contraindications to EXIT.[7] Depending on the confidence and experience of the resuscitation team, the airway surgeon may still be requested in the delivery suite to be ready for bronchoscopy or tracheostomy after delivery. Hard contraindications include any congenital anomaly that indicates fetal nonviability.

Equipment

The required equipment for an EXIT procedure can vary significantly based on the evaluation performed during the workup phase and the planned EXIT type. Given the mother's open surgical site, the airway equipment must be kept sterile in these circumstances. Generally, all EXIT procedures require the following equipment:

• Anesthesia circuits for both mother and fetus with invasive maternal blood pressure monitoring
• Foley catheter
• Two large-bore peripheral intravenous lines
• Type-and-crossed blood for possible maternal transfusion in the room
• Possible epidural catheterization
• Ultrasound machine with a sterile sleeve
• Cesarean delivery surgical set
• Electrocautery
• Uterine stapling device
• Amnioinfusion
• Fetal resuscitation bay
• Optional adjacent operating room set up ready to receive infant

EXIT-to-resection and EXIT-to-separation of congenital twins may require additional surgical equipment specific to the procedure being performed. EXIT-to-ECMO procedures require an ECMO unit and trained support staff. EXIT-to-airway procedures may also require the following supplies:

• Pediatric airway cart
  • Pediatric laryngoscopes
  • Endotracheal tubes: 3.0 mm cuffed, 3.0 mm uncuffed, 2.5 mm uncuffed
  • Pediatric airway cart with supplies for direct laryngoscopy and removal of tracheal clip or balloon if indicated
• Pediatric tracheostomy tray

Personnel

Ideally, the following specialists and staff are part of a designated team that performs these procedures together whenever needed in this high-pressure environment; team cohesion could be the difference between success and failure. Team members are specialized in caring for maternal or fetal patients, including the following:

• Maternal team
  • Obstetric anesthesiologist
  • Obstetrician
  • Circulating nurse
  • Surgical technician
• Fetal team
  • Neonatal anesthesiologist
  • Pediatric surgeon
  • Pediatric otolaryngologist
  • Neonatal intensivist
  • Possible ECMO team
  • Possible pediatric cardiology or cardiothoracic surgery
  • Circulating nurse
  • Surgical technician

Preparation

Once a mother and fetus are identified as candidates for the procedure, expeditious referral to a center practicing EXIT should be pursued. A thorough prenatal workup should be conducted to give the parents and treating team the information to make the best decision regarding a treatment plan. Early identification of features such as polyhydramnios and hydrops fetalis, which increase the risk of preterm delivery, is essential as a key to successful EXIT, a planned, controlled procedure before spontaneous labor and delivery ensue.[24]

Imaging in preparation for EXIT procedures typically begins with ultrasonography to characterize most lesions necessitating the procedure. Ultrasonography can also visualize placental anomalies that may make hysterotomy difficult or dangerous. More advanced 3- and 4-dimensional ultrasounds and fetal MRIs are often used to work up the anomaly further once the patients reach a tertiary care center.[25][26] Even more advanced options include virtual bronchoscopy, in which a 3-dimensional video of the fetal airway is built from MRI imaging, or a 3-dimensional printing of the airway. Fetal tracheoscopy is a rare invasive option in which the airway is directly examined through a trans-placental trocar. Interventions have also been performed this way, including intubation with a standard 2.5 mm endotracheal tube.[27][28]

Preparing the operating room and the involved medical and surgical teams is paramount on the day of the procedure. The operating room should be prepared with the required equipment as indicated by the specific EXIT type. Ideally, the teams are composed of experienced clinicians who work together often and have some continuity. Rehearsal of the procedure with all team members involved is usually performed before the actual procedure. Preparation for massive bleeding and transfusion is critical as the average maternal blood loss during EXIT has been estimated at 1 L.[29]

Technique or Treatment

EXIT-to-Airway Surgery

The mother is brought into the room and positioned either supine or with a tilt to the left to take pressure off the vena cava. The placental location must be confirmed via ultrasonography before any incisions are made. The abdomen is then prepped and draped in standard fashion for cesarean delivery. A laparotomy is made, and the uterus is exposed. Sterile ultrasound can be used at this point for a final confirmation of hysterotomy location. The hysterotomy is made, and the fetal head, neck, and torso are delivered. Amnioinfusion with warmed lactated ringers is set up to ensure the umbilical cord is not compressed. Although fetal anesthesia is accomplished through the placenta, a small-bore catheter is usually placed, and the fetus is anesthetized further with opioids and muscle relaxants. Fetal vital signs are monitored closely.

Airway interventions are then started. Initially, intubation via direct laryngoscopy is usually attempted. Adjuncts may include manual distraction of a mass, use of stylets, needle decompression of fluid-filled masses, and partial resections of solid masses. An alternative is upper airway evaluation with a rigid or flexible laryngoscope, followed by the Seldinger technique. Once the airway is identified with the device of choice, a bougie-stylet, flexible laryngoscope, or Hopkins rod can be used to advance the endotracheal tube into position. If anterograde intubation attempts are deemed ineffective, retrograde intubation may be attempted, which involves dissecting the trachea, creating a tracheostomy incision, and feeding a 4- or 8-French nasogastric tube into the mouth. An endotracheal tube is then fixed to the nasogastric tube and pulled into place, and the tracheostomy is closed. However, if closure is impossible, the tracheostomy is formalized. After the airway is secured, other interventions, such as resection of mass or separation of congenital twins, may be pursued.

Current EXIT procedure protocols create about a 90-minute window for securing the airway.[5][6] Once the airway is secured, the infant is ventilated, and the umbilical cord is clamped. The delivery then proceeds as normal, handing off the infant to the waiting neonatal intensivist team for resuscitation. This step requires direct communication between the anesthesiologist and surgeons, as uterotonics must replace the tocolytics administered during EXIT. Control of maternal hemorrhage is the sole focus of the surgical team at this time. The surgical site is closed, and the mother is transferred to either the intensive care unit or maternal ward for recovery, depending on her status during the case.

Complications

Maternal Complications

The primary maternal risk during EXIT is hemorrhage. Predisposing factors include prolonged uterine relaxation, larger hysterotomy than standard cesarean delivery, and a higher likelihood of placental injury. Despite this, results from retrospective studies have shown that only 6% of mothers require intraoperative blood transfusion. The risk of surgical site infection is also higher than a standard Cesarean delivery at 15% versus 2%, respectively, because of prolonged operative time. A decrease in future fertility and increased risk of uterine complications in future pregnancies were thought to be long-term risks of the procedure, but studies have not supported this.[6][30]

Fetal Complications

Intrapartum risks to the fetus are mainly related to cardiac dysfunction secondary to maternal anesthetic overdose, maternal hypotension leading to placental hypoperfusion, direct injury to the placenta or placental abruption, and cord compression.[31] Risks of mass resection include nerve or vascular injury, bleeding, and surgical site infection. The inability to secure the airway and fetal demise are the most significant risks. The incidence of these complications is not currently well reported in the literature.

Clinical Significance

While not common or well-known in the general medical community, the EXIT procedure is lifesaving to most infants needing airway intervention at the time of delivery. Mortality rates of upper airway malformation, head and neck mass, cardiopulmonary malformations, and other specific congenital maladies have drastically declined after the introduction of appropriate prenatal evaluation, team preparation, and meticulous surgical technique. However, EXIT procedures are not without risk to the mother or child, but the possibility of a healthy delivery typically outweighs these risks.[32]

Enhancing Healthcare Team Outcomes

The EXIT procedure demands high interprofessional collaboration among physicians, advanced practitioners, nurses, pharmacists, and other health professionals to optimize patient-centered care, outcomes, patient safety, and team performance. This complex operation necessitates secure communication and physical cooperation among clinicians, alongside skillful support staff participation from various roles such as nurses, surgical technicians, and radiology technicians. Enhancing teamwork and outcomes involves several specific measures, including interprofessional meetings with the patient before the procedure to ensure comprehensive care planning, rehearsal of the procedure to familiarize team members with their roles and responsibilities, and efforts to maintain continuity of team members from procedure to procedure to preserve team chemistry and efficiency. By fostering effective interprofessional communication, coordination, and collaboration, healthcare teams can ensure the safe and successful execution of EXIT procedures, ultimately improving patient outcomes and satisfaction.