Advances in prenatal imaging in the last 20 years have enabled prenatal diagnosis of obstructive head and neck masses. These advances, coupled with improvements in maternal-fetal anesthesia, have made possible the development of the ex utero intrapartum treatment (EXIT) procedure for management of obstructive head and neck masses, during which the airway is managed in a controlled fashion while maintaining fetal circulation for oxygenation. This review addresses the preoperative and perioperative assessment and management of patients with prenatally diagnosed airway obstruction, indications and contraindications for the EXIT procedure, technical details of the procedure, and outcomes.
Key points
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The ex utero intrapartum treatment (EXIT) procedure allows partial delivery of a fetus with prenatally diagnosed airway obstruction in a controlled fashion, allowing continued placental function while the fetal airway is secured.
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The EXIT procedure requires input from a coordinated multidisciplinary team including representatives from anesthesiology, maternal-fetal medicine, neonatology, nursing, respiratory therapy, and pediatric otolaryngology.
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Despite advancements in the procedure, patients requiring EXIT are uniformly critically ill.
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Extensive counseling regarding the risks of the procedure, the appropriateness of the procedure, and alternative management strategies should be reviewed with the family before deciding whether to proceed.
Introduction
Neonatal airway obstruction that is diagnosed at delivery creates an emergent situation with high morbidity. This obstruction may be either intrinsic (due to abnormalities in laryngotracheal development) or extrinsic (from a congenital head and neck mass or anatomic deformation). Every situation requires an individualized approach to secure the airway that often uses specialized equipment and personnel. In the last 20 years, advances and innovations have been made in prenatal imaging, maternal and fetal anesthesia, and fetal surgery that have significantly altered the management of patients with congenital airway obstruction. Owing to widespread use of prenatal ultrasonography, patients with airway obstruction can now be prenatally diagnosed. Often the degree of obstruction can also be estimated. With advances in fetal surgery, congenital malformations that were previously considered to be untreatable or lethal can be ameliorated, leading to improved neonatal viability. Advances in maternal-fetal anesthesia have enabled a transition from the light anesthesia and increased uterine tone typical of traditional cesarean section to the deep anesthesia and uterine relaxation that facilitates maintenance of uteroplacental circulation and fetal anesthesia. The confluence of these advances has allowed development of the ex utero intrapartum treatment (EXIT) procedure, whereby prenatally diagnosed patients with airway obstruction undergo partial delivery and, while maintained on placental support, undergo airway instrumentation to secure the airway before completion of delivery and umbilical cord clamping.
Development of the Ex Utero Intrapartum Tracheoplasty Procedure
Although the EXIT procedure was initially developed for the management of congenital diaphragmatic hernia (CDH), allowing a controlled intrapartum setting in which a previously placed tracheal clip, plug, or balloon could be removed and the airway assessed, the procedure quickly was adopted for the management of congenital airway obstruction. There are multiple published reports and case series describing intrapartum airway management, but these reports used either vaginal delivery or standard cesarean delivery techniques without consideration for the maintenance of amniotic fluid volume to prolong uteroplacental circulation. Contemporaneous with the initial descriptions of EXIT for the management of congenital diaphragmatic hernia was the initial description of the operation on placental support (OOPS), which discussed the need for uterine relaxation and used subtotal delivery of the fetus, although no specific mention of maintenance of uterine volume is made. Although this report by Skarsgard and colleagues represents the first description of controlled intrapartum airway management of congenital airway compression, the first description of the EXIT procedure as it is known today is credited to Mychaliska and colleagues in 1997, in which they present CDH data that include 2 reports of EXIT for lymphatic malformations of the neck and oropharynx. Whether because of the dubious nature of Skarsgard’s chosen acronym (OOPS) or true differences in surgical technique, the preferred terminology has remained EXIT in subsequent literature.
Expansion of Indications for Procedure
Following the initial description of EXIT, its indications have expanded to include 4 broad categories: EXIT to airway, EXIT to resection, EXIT to extracorporeal membranous oxygenation (ECMO), and EXIT to separation. Specific indications within these categories are outlined in Table 1 . As the focus herein is on the role of the otolaryngologist–head and neck surgeon in EXIT, the remaining discussion is limited to EXIT procedures performed for congenital head and neck anomalies producing either intrinsic or extrinsic airway obstruction. This review presents the preoperative and perioperative assessment and management of patients with prenatally diagnosed airway obstruction, indications and contraindications for the EXIT procedure, technical details of the procedure, and outcomes.
| Obstruction Source | Examples | |
|---|---|---|
| EXIT to airway | Extrinsic | Teratoma (cervical, pharyngeal, epignathus) |
| Lymphatic/vascular malformation | ||
| Congenital giant ranula | ||
| Severe micrognathia | ||
| Intrinsic | Congenital high airway obstruction syndrome (CHAOS) | |
| Iatrogenic | Tracheal clipping or Balloon occlusion in congenital diaphragmatic hernia | |
| EXIT to resection | Thoracic/mediastinal masses | |
| Congenital cystic adenomatoid malformations (CCAM) | ||
| Bronchopulmonary sequestration | ||
| Fetal lobar interstitial tumor | ||
| Mediastinal teratoma | ||
| EXIT to ECMO | Severe congenital heart disease | |
| Severe congenital diaphragmatic hernia | ||
| EXIT to separation | Conjoined twins |
Introduction
Neonatal airway obstruction that is diagnosed at delivery creates an emergent situation with high morbidity. This obstruction may be either intrinsic (due to abnormalities in laryngotracheal development) or extrinsic (from a congenital head and neck mass or anatomic deformation). Every situation requires an individualized approach to secure the airway that often uses specialized equipment and personnel. In the last 20 years, advances and innovations have been made in prenatal imaging, maternal and fetal anesthesia, and fetal surgery that have significantly altered the management of patients with congenital airway obstruction. Owing to widespread use of prenatal ultrasonography, patients with airway obstruction can now be prenatally diagnosed. Often the degree of obstruction can also be estimated. With advances in fetal surgery, congenital malformations that were previously considered to be untreatable or lethal can be ameliorated, leading to improved neonatal viability. Advances in maternal-fetal anesthesia have enabled a transition from the light anesthesia and increased uterine tone typical of traditional cesarean section to the deep anesthesia and uterine relaxation that facilitates maintenance of uteroplacental circulation and fetal anesthesia. The confluence of these advances has allowed development of the ex utero intrapartum treatment (EXIT) procedure, whereby prenatally diagnosed patients with airway obstruction undergo partial delivery and, while maintained on placental support, undergo airway instrumentation to secure the airway before completion of delivery and umbilical cord clamping.
Development of the Ex Utero Intrapartum Tracheoplasty Procedure
Although the EXIT procedure was initially developed for the management of congenital diaphragmatic hernia (CDH), allowing a controlled intrapartum setting in which a previously placed tracheal clip, plug, or balloon could be removed and the airway assessed, the procedure quickly was adopted for the management of congenital airway obstruction. There are multiple published reports and case series describing intrapartum airway management, but these reports used either vaginal delivery or standard cesarean delivery techniques without consideration for the maintenance of amniotic fluid volume to prolong uteroplacental circulation. Contemporaneous with the initial descriptions of EXIT for the management of congenital diaphragmatic hernia was the initial description of the operation on placental support (OOPS), which discussed the need for uterine relaxation and used subtotal delivery of the fetus, although no specific mention of maintenance of uterine volume is made. Although this report by Skarsgard and colleagues represents the first description of controlled intrapartum airway management of congenital airway compression, the first description of the EXIT procedure as it is known today is credited to Mychaliska and colleagues in 1997, in which they present CDH data that include 2 reports of EXIT for lymphatic malformations of the neck and oropharynx. Whether because of the dubious nature of Skarsgard’s chosen acronym (OOPS) or true differences in surgical technique, the preferred terminology has remained EXIT in subsequent literature.
Expansion of Indications for Procedure
Following the initial description of EXIT, its indications have expanded to include 4 broad categories: EXIT to airway, EXIT to resection, EXIT to extracorporeal membranous oxygenation (ECMO), and EXIT to separation. Specific indications within these categories are outlined in Table 1 . As the focus herein is on the role of the otolaryngologist–head and neck surgeon in EXIT, the remaining discussion is limited to EXIT procedures performed for congenital head and neck anomalies producing either intrinsic or extrinsic airway obstruction. This review presents the preoperative and perioperative assessment and management of patients with prenatally diagnosed airway obstruction, indications and contraindications for the EXIT procedure, technical details of the procedure, and outcomes.
| Obstruction Source | Examples | |
|---|---|---|
| EXIT to airway | Extrinsic | Teratoma (cervical, pharyngeal, epignathus) |
| Lymphatic/vascular malformation | ||
| Congenital giant ranula | ||
| Severe micrognathia | ||
| Intrinsic | Congenital high airway obstruction syndrome (CHAOS) | |
| Iatrogenic | Tracheal clipping or Balloon occlusion in congenital diaphragmatic hernia | |
| EXIT to resection | Thoracic/mediastinal masses | |
| Congenital cystic adenomatoid malformations (CCAM) | ||
| Bronchopulmonary sequestration | ||
| Fetal lobar interstitial tumor | ||
| Mediastinal teratoma | ||
| EXIT to ECMO | Severe congenital heart disease | |
| Severe congenital diaphragmatic hernia | ||
| EXIT to separation | Conjoined twins |
Treatment goals and planned outcomes
Goals
Stated simply, the goal of the EXIT procedure is to convert what was formerly an emergent procedure, establishing a neonatal airway, into a controlled procedure. This overarching goal is achieved by using a multidisciplinary team approach whereby each team member accomplishes individual objectives.
Radiology and maternal-fetal medicine
The goals of the radiologist and maternal-fetal medicine specialist are to accurately diagnose fetal pathophysiology and aid in the selection of appropriate candidates for EXIT. This prenatal diagnostic information was initially obtained using 2-dimensional ultrasonography. Advances in ultrasound technology now allow for 3-dimensional and 4-dimensional imaging, which provide additional detail and 3-dimensional renderings of fetal anatomy. Detailed imaging has sometimes identified patients who do not require EXIT and who can be managed by means of traditional delivery. If airway obstruction is suspected based on findings identified on ultrasonography, a fetal magnetic resonance (MR) image is obtained to further delineate the anatomy. MR imaging has been shown to have greater than 90% sensitivity for predicting the etiology of obstructive lesions in these situations. Ultrasonography can have an intraoperative role in confirmation of fetal position, ultrasound-guided cyst decompression, and mapping of placental edges before hysterotomy so as to avoid maternal hemorrhage.
Anesthesia
The goals of the anesthesia team are to achieve a deep plane of anesthesia while maintaining uterine relaxation and maternal blood pressure and blood flow to the uterus. In addition, the anesthesia team must consider the impact of the maternal anesthetic on the fetus. In contrast to cesarean delivery, the transmission of anesthetic to the fetus is desired in the EXIT procedure, as the fetus may require multiple stimulating interventions to secure the airway. To achieve these goals, multiple anesthetic techniques have been published. All, at their root, include achieving a deep general anesthetic; either by use an inhaled anesthetic titrated to 2 to 3 minimum alveolar concentration (MAC), or by using a combination of intravenous anesthetics (such as propofol and a narcotic), with a lower MAC of inhaled anesthetic gas. In addition, ephedrine is used as needed to support maternal blood pressure, and nitroglycerin is added as needed to augment uterine relaxation.
Obstetrics
The goals of the maternal-fetal medicine team are to maintain uteroplacental circulation, ensure safe delivery of the fetus, limit maternal blood loss, and ensure maternal safety. Achieving these goals requires the careful planning of the hysterotomy incision using a hemostatic stapler. Also, preincision mapping of placental edges so it can be avoided helps prevent maternal hemorrhage and continue placental circulation. In addition, securing the amniotic membranes to the uterine wall and using amnioinfusion will aid in the maintenance of uterine amniotic fluid volume, which contributes to the long-term maintenance of placental circulation. Following successful fetal airway instrumentation, the obstetric team works in concert with the anesthesia team to complete delivery of the fetus, repair the uterus, and reverse uterine relaxation.
Otolaryngology
The goal of the otolaryngology team is to secure the fetal airway. Following partial delivery of the fetus, a preplanned algorithm (see later description) is followed in an ascendingly invasive manner as needed.
Neonatology
The goal of the neonatology team is to stabilize the neonate following delivery. This task is made difficult in part by the potential pulmonary problems that may accompany EXIT deliveries. There are published case reports describing pulmonary hypoplasia thought to be due to extreme fetal neck flexion, caused by a congenital neck mass compressing the lungs against the thoracic outlet. The presence of an experienced neonatology team is essential to the care of the critically ill neonate. In addition, the neonatal team must ensure adequate sedation and analgesia of the neonate. Recent literature suggests that the pain response is intact in the late-term fetus, and early exposure to painful stimuli may alter the development of central pathways.
Indications and Contraindications
Indications
The EXIT procedure may be considered in cases where there is a prenatally diagnosed upper airway obstruction that would be lethal or potentially lethal if traditional delivery were undertaken. Primarily, these obstructions are caused by head and neck teratoma, lymphatic/vascular malformations, severe micrognathia, and congenital high airway obstruction syndrome (CHAOS). Other unique indications, such as congenital giant ranula and fetal epignathus, have also been described. Not every prenatally diagnosed head and neck mass requires EXIT. Specific indications have been suggested as criteria for use of the EXIT procedure. These criteria include the diagnosis of a teratoma, mass size greater than 5 cm, polyhydramnios or absence of fetal gastric fluid suggesting obstruction of the alimentary canal, or signs of intrinsic airway obstruction such as hyperexpanded lungs or flattened diaphragm. Ultimately, any airway anticipated to be difficult based on review of prenatal imaging also warrants consideration by the EXIT team.
Teratoma
Teratoma is a germ cell tumor that can occur in the fetal head and neck. Teratomas can present from mandible to clavicle, and can extend into the tongue and floor of the mouth. These tumors are characterized by components from all germ cell layers and rarely have malignant potential. Typically they originate near midline and tend to compress the aerodigestive tract against the spine, rather than distorting the location of the airway. When compared with all patients with obstructive head and neck masses, patients with teratoma are more likely to require surgical intervention during EXIT, likely because of the solid incompressible nature of teratoma that makes exposure of the larynx with direct laryngoscopy difficult. Teratomas also have a propensity for intratumoral hemorrhage. For these reasons, even if there is no airway obstruction at birth, intubation to secure the airway and excision of the lesion as soon as possible has been recommended. Though typically isolated anomalies, teratoma can be associated with chondrodystrophia fetalis, imperforate anus, hypoplastic left heart, mandibular hypoplasia, and Patau syndrome.
Lymphatic/vascular malformation
Lymphatic malformation (LM) is the most common head and neck indication for EXIT, and occurs most frequently in the head and neck. These lesions tend to be more infiltrative than teratoma in tissues, and tend toward displacement of the aerodigestive tract rather than compression of the lumen against the spine. LMs demonstrate a bimodal distribution with respect to timing of appearance in fetal development, with important implications for incidence of associated chromosomal anomalies, location of the malformation, and outcome. LMs identified early in the second trimester arise most commonly in the posterior triangle of the neck, are associated with chromosomal anomalies in 60% of cases, have multiple associated structural anomalies, and are associated with hydrops and a high mortality. However, LMs identified in the third trimester or diagnosed at birth arise in a more anterior position, are rarely associated with chromosomal anomalies, and have a much lower mortality. Use of the de Serres staging and Cologne Disease Score for LMs have been used to predict complications and clinical outcomes. After establishment of a secure airway and safe delivery, LMs can be managed with surgical excision or sclerotherapy.
Severe micrognathia
The micrognathic (underdeveloped) and retrognathic (retrodisplaced) mandible caused by mandibular hypoplasia can displace the tongue base, obstructing the aerodigestive tract. In the most severe cases, the obstruction is to a degree that endotracheal intubation and respiration are likely impossible. As a result of fetal inability to swallow amniotic fluid, polyhydramnios develops during gestation. Only the most severe cases of mandibular hypoplasia require EXIT. Management by endotracheal intubation over a flexible fiberoptic bronchoscope by itself or via an intubating laryngeal mask airway such as the Air-Q (Mercury Medical, Clearwater, FL, USA) can be used in most cases of micrognathia to secure the airway. The jaw index has been developed to diagnose micrognathia, measuring the ratio of the difference of the anterior and posterior mandibular diameter to the biparietal diameter. Micrognathia is diagnosed with 100% specificity and 98.1% sensitivity when the jaw index is less than 23. Several investigators have applied the jaw index and have identified several factors that increase the likelihood for requiring perinatal intervention such as EXIT. These factors include objective findings of a jaw index less than the fifth percentile and findings suggestive of esophageal obstruction (ultrasonography suggesting polyhydramnios or the absence of a gastric bubble), or MR imaging evidence of glossoptosis.
Congenital high airway obstruction syndrome
CHAOS encompasses a spectrum of disease from laryngeal web to complete laryngeal and/or tracheal stenosis. It is defined radiographically by a triad of ultrasonographic findings: large echogenic lungs, flattened or everted diaphragm, and dilated airways distal to the site of obstruction. With complete obstruction, ascites and, ultimately, hydrops develop from lymphatic and cardiac compression, with the potential for fetal demise. As a result, fetuses with CHAOS require frequent monitoring so that intervention may be undertaken at the time ascites is found to develop. In some cases, a small tracheoesophageal fistula or pinpoint tracheal/laryngeal lumen allows for decompression of the hyperinflated lungs, with cessation of the progression to hydrops. However, if no such “release valve” exists and the patient progresses toward ascites and polyhydramnios, fetoscopic intervention can be undertaken and wire tracheoplasty performed to create a route for decompression. Whereas CHAOS is most frequently a sporadic finding, laryngotracheal atresia can be associated with chromosomal anomalies or Fraser syndrome (laryngeal anomalies, cryptophthalmos, syndactyly, genitourinary tract malformations, craniofacial anomalies, orofacial clefting, mental retardation, and musculoskeletal anomalies). There is also a suggestion of a possible autosomal dominant inheritance pattern. In the presence of other anomalies, prenatal and perinatal mortality increase, a situation that must be thoroughly reviewed during preoperative counseling. Whereas CHAOS was previously fatal, EXIT has allowed the controlled delivery of affected fetuses, confirmation of the diagnosis with bronchoscopy, and establishment of the airway with tracheostomy. EXIT has transitioned CHAOS from a uniformly lethal condition to a surgically manageable disease. CHAOS remains a condition with the potential for significant long-term morbidity, including ventilator dependence and the need for airway reconstruction.
Contraindications
The EXIT procedure is a high-risk procedure for two patients. As such, a thorough consideration of the risks, both maternal and fetal, must be weighed against the likelihood of achieving the potential benefits. Instances in which the balance of risks to benefits is shifted more toward incurring additional maternal and fetal risk with low likelihood of benefit represent contraindications to proceeding with EXIT.
Maternal
No absolute contraindications to EXIT exist from a maternal standpoint. From a technical standpoint, uterine anomalies and placental position may significantly increase the technical difficulty of the procedure, but these considerations do not represent absolute contraindications. Moreover, the concern for increased risk of maternal complications has been discussed as a relative contraindication to EXIT. Reports have demonstrated a significant increase in maternal blood loss and superficial wound infection in comparison with cesarean section, but no difference was appreciated in hematocrit change or incidence of endometritis or in overall infectious complications. These findings suggest that the statistically significant differences may not have clinical significance. More recent reports have demonstrated that EXIT represents a safe option with risks similar to those of cesarean section. In the obstetric literature, a recent publication suggests that the benefits of EXIT far outweigh maternal risks.
Fetal
Fetal considerations represent the more likely source of contraindications to EXIT. Critical evaluation of prenatal imaging may suggest that the neonatal airway would be attainable after delivery with the use of direct laryngoscopy or laryngeal mask airway, without need for placental support. In a recent report from Lazar and colleagues, one-third of patients referred for EXIT did not require the procedure because of minimal tracheal involvement. On the opposite end of the spectrum, cases of CHAOS with complete tracheal agenesis may not allow successful tracheostomy to be performed, making EXIT delivery a futile exercise. Moreover, consideration of the viability of the neonate, accounting not only for the gravity of the airway anomaly but also considering any other concomitant anomalies, should be carefully weighed before electing to proceed with EXIT. Certain causes of obstruction (eg, cervical teratoma and LM) are associated with other chromosomal abnormalities. When present, the mortality of EXIT increases to more than 36%. This risk must be assessed and considered in discussions with the family. However, the mortality of non-EXIT delivery in patients with obstructive head and neck lesions is approximately 80%, a factor that must be considered when deciding to offer EXIT.
Special consideration must also be taken in the case of a multiple fetal pregnancy. If the EXIT procedure is performed for the benefit of one fetus with an obstructed airway, but will expose the other nonobstructed fetus to a significant level of risk, the procedure should be subject to an additional level of scrutiny. In this case and in any case where the ratio of risks to benefits is not clear, an independent ethical consultation should be considered.
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