Fetal Surgery

The EXIT Procedure: Principles, Pitfalls and Progress

Abstract

Although performing procedures on a fetus prior to cutting the umbilical cord has previously been reported, the principles of the Ex-Utero Intrapartum Treatment / EXIT procedure were first fully developed in its use in reversing tracheal occlusion in severe congenital diaphragmatic hernia.

The EXIT offers the advantage of insuring uteroplacental gas exchange while on placental support. The lessons learned in the development of the principles that underlie the EXIT procedure have been successfully applied in other conditions to improve the outcome, most notably in cases of airway obstruction.

The range of indications for the EXIT procedure has expanded to include giant fetal neck masses, lung or mediastinal tumors, congenital high airway obstruction syndrome and EXIT to ECMO (extracorporeal membrane oxygenation), among others.

This review is intended to summarize the principles that underlie the technique, the pitfalls of misapplication of these principles, the expanding indications, and progress in successful application of the EXIT procedure.

Introduction

Advances in prenatal diagnosis of fetal congenital malformations, in particular tumors or malformations involving the fetal airway, have provided the opportunity for the development of a strategy to convert potentially catastrophic situations during delivery to a controlled environment. These conditions constitute an immediate threat to the newborn airway with the risk of hypoxia, ischemic brain injury and / or death.

Numerous case reports described operating prior to cutting the umbilical cord usually simply to intubate or perform bronchoscopy (1). However, it was recognized that there was more to preserving uteroplacental gas exchange than maintaining the umbilical cord intact. Skarsgard et al described Operating on Placental Support, or the OOPS procedure, in the treatment of a fetus with anticipated airway obstruction (2). Subsequently, the EXIT procedure was described for the reversal of in utero tracheal occlusion performed in cases of severe congenital diaphragmatic hernia (3).

These cases require neck exploration for the removal of the tracheal clips with maintenance of utero-placental blood flow until the fetal airway is secured by endotracheal intubation. In previous reports using intrapartum laryngoscopy or bronchoscopy during cesarean section, or even vaginal delivery without clamping the cord (4) there was no attempt to prevent uterine contraction, or the fetus was entirely removed from the uterus resulting in loss of uterine volume.

In both instances, cessation of uteroplacental circulation would be expected. In contrast, the central principle of the EXIT procedure is controlled uterine hypotonia to preserve uteroplacental circulation. Experience with the EXIT technique demonstrated fetal and maternal hemodynamic stability and soon led to expanded indications for its use.

The indications broadened to include giant fetal neck masses, fetal mediastinal or lung masses such as congenital cystic adenomatoid malformation (CCAM), and congenital high airway obstruction syndrome (CHAOS) among others.

The EXIT Procedure is not a Cesarean Section

A common misconception is that an EXIT procedure is merely a cesarean section. During a cesarean section (C-section), the goals of the procedure are to:

1. Maximize the uterine tone to prevent postpartum hemorrhage
2. Minimize the transplacental diffusion of inhalational anesthetic agents to avoid neonatal depression (if done under general anesthesia)

In contrast, during the EXIT procedure, the goals are:

1. To achieve a state of uterine hypotonia to maintain the uteroplacental circulation using deep general anesthesia
2. To preserve uterine volume to prevent placental abruption
3. To reach a deep plane of maternal anesthesia but maintain normal maternal blood pressure
4. Achieve a surgical level of fetal anesthesia without cardiac depression

In addition, the EXIT procedure requires synchronized team work involving multiple disciplines including at least one or two pediatric surgeons, or a pediatric ENT, a maternal fetal medicine specialist or obstetrician, an echocardiographer, a neonatologist, two anesthesiologists, two circulating nurses and two scrub nurses.

Maternal Anesthetic Considerations

Unlike standard obstetric anesthetic practice in which regional anesthesia is the rule, general anesthesia is the technique of choice for the EXIT procedure. The EXIT procedure like any other form of fetal surgery involves the treatment of two patients; the mother and her baby. For this reason we usually have an anesthesiologist for the mother and another for the baby. There are a number of maternal and fetal anesthetic considerations that must be continuously monitored.

The physiology of pregnancy contributes to a number of maternal and fetal anesthetic risks. The mother is at increased risk for aspiration pneumonitis due to the effects of pregnancy lowering the pressure of the lower esophageal sphincter, the increased pressure of the gravid uterus on the stomach, and increased gastric acid production. The cardiovascular system is also affected during pregnancy.

A decrease in the preload during supine positioning can cause maternal hypotension, decreased uterine artery perfusion and thus fetal hypoxia. Therefore it is important to place the mother with a left uterine displacement to maximize venous return to the heart and preserve an adequate maternal cardiac output. In pregnancy there is an expanded blood volume, but lower hematocrit and an increase in peripheral venous capacity.

Pregnancy also affects the pulmonary function with decrease in functional residual capacity putting the mother at an increased risk for hypoxia. For these reasons, maternal anesthesia is induced through a rapid sequence technique using thiopental (5mg/kg), succinylcholine (2mg/kg) and fentanyl (1-2µg/kg) given intravenously followed by endotracheal intubation. This is followed by paralysis using intravenous vecuronium titrated by peripheral nerve stimulation.

Fetal anesthetic considerations

Support of the fetus during the EXIT procedure depends entirely on preservation of uteroplacental gas exchange. Both uterine and umbilical artery blood flow influence fetal oxygenation. Uterine artery blood flow is affected by maternal systemic blood pressure and myometrial tone. Volatile anesthetics used during the EXIT procedure not only decrease myometrial tone but also tend to decrease both maternal blood pressure and placental blood flow.

This can result in a decrease in fetal oxygenation (5). Therefore, maintenance of maternal blood pressure within 10% of baseline is critical for adequate fetal oxygenation during the EXIT procedure. The maintenance of maternal blood pressure is achieved using ephedrine to counteract the hypotensive effects of the high concentrations of inhalational agents used in EXIT procedures.

Ephedrine acts selectively on the peripheral vascular resistance sparing the placental circulation (6). Uteroplacental gas exchange is also dependent upon umbilical artery blood flow which is influenced by fetal cardiac output and placental vascular resistance. Therefore, preservation of fetal cardiac output is important to maintain fetal oxygenation.

The cardiovascular physiology of the fetus is different from full term neonates in that the cardiac output is more dependent on heart rate rather than stroke volume. In addition, the high vagal tone and low baroreceptor sensitivity cause the fetus to respond to stress with a decrease in heart rate.

The fetus primarily relies on increased heart rate to increase cardiac output and blood flow re-distribution in response to stress to preserve oxygenation for the brain at the expense of the rest of the body.

In addition to the peculiar characteristics of fetal physiology, inhalational anesthetics also cause a direct fetal myocardial depression, vasodilatation, and changes in arterio-venous shunting which can lead to fetal hemodynamic instability (7).

These physiologic differences and responses to anesthetic agents require continuous fetal monitoring to ensure uncompromised uteroplacental gas exchange and fetal well being.

The inhalational anesthetic regime used during the EXIT procedure passes through two different stages; at first anesthesia is maintained with 0.5 MAC (minimal alveolar concentration) of either, Desflurane, Isoflurane or Sevoflurane in oxygen. The anesthetic is then increased to two MAC before maternal incision and then subsequently increased as needed before hysterotomy to achieve desired relaxation of uterine tone.

Occasionally a tocolytic is given to augment the uterine relaxation. A number of tocolytic agents can be used as an adjunct to inhalational agents including indomethacin, terbutaline or nitroglycerine. Indomethacin may also prevent prostaglandin mediated increases in placental resistance independent of its effects on uterine tone (8).

Maintenance of uterine volume is also important to prevent uterine contraction. This is accomplished by preventing the fetus from completely delivering and the use of amnio-infusion with warm Ringer’s lactate solution administered via Level I rapid infusion device to prevent cord compression.

The second critical stage of the anesthetic technique comes in anticipation of clamping of the cord and ending the EXIT procedure. During this stage coordination between the surgical and anesthesia teams is crucial to prevent uterine atony and excessive maternal bleeding.

The volatile anesthetic is decreased to 0.5 MAC or turned off entirely to allow uterine tone to return to normal, followed by administration of oxytocin 20U in 500ml of normal saline intravenously as a bolus followed by 10 U in 1000 ml drip titrated to enhance uterine contraction.

Further measures are taken to decrease the risk of uterine atony such as uterine massage and administration of 0.25 mg methergine and 250µg carboprost (F2-alpha prostaglandin) via intramuscular or intravenous injection if needed. After skin closure, the inhalational anesthetic is discontinued and 100% oxygen is administered. Maternal paralysis is reversed by the use of glycopyrolate (10µg/kg), and neostigmine (0.7mg/kg) and the patient is extubated after spontaneous breathing is observed (9).

Fetal anesthesia is provided primarily through the transplacental passage of the volatile anesthetics. However, this takes about an hour to reach 70% of the maternal levels. Therefore, before fetal incision, a cocktail of 10-20µg/kg fentanyl, 20µg/kg atropine and 0.2mg/kg vecuronium is administered intramuscularly to supplement anesthesia and provide for postoperative analgesia.

Maternal and fetal monitoring

Close maternal and fetal monitoring during the EXIT procedure aim at the early recognition and management of problems as they arise. Maternal monitoring includes invasive arterial blood pressure monitoring (arterial line) to safeguard against any maternal hypotension that will jeopardize fetal oxygen transport, continuous electrocardiography, pulse oximetry and end-tidal CO2 monitor.

Continuous fetal monitoring is of paramount importance during the EXIT procedure. Fetal arterial saturation is monitored by a reflectance pulse oximeter placed on the fetal hand and wrapped with foil to decrease ambient light exposure (10). Normal fetal arterial saturation is 60 to 70%, although values greater than 40% represent adequate fetal oxygenation. Continuous intraoperative fetal echocardiography is also used to monitor fetal cardiovascular function (11). The use of fetal echocardiography helps to identify early problems like:

• Decreased filling
• Fetal bradycardia
• Decreased myocardial contractility
• Ductal constriction
• Atrioventricular valve incompetence

	An intraoperative view during an EXIT procedure demonstrating continuous fetal monitoring using a sterile echocardiography, reflectance pulse oximetry and IV access lines.

These are all signs of fetal distress that require prompt treatment. Fetal arterial or venous blood gases may be obtained through umbilical vessel puncture during periods of fetal distress to guide in therapy. An intravenous access is essential to allow administration of fluids, blood, or medications for inotropic support when needed.

Technique

The decision to enter the abdomen through a low transverse skin incision or through a midline fascial incision is based on the placental location, predicted site of hysterotomy and the indication for EXIT. The incision of choice is usually a low transverse abdominal incision unless anterior position of the placenta necessitates a posterior hysterotomy, in which case, a midline laparotomy will be required. After laparotomy, the uterus is examined for adequacy of myometrial relaxation and concentration of inhalational agents adjusted as necessary.

Before fashioning the hysterotomy, precise sonographic mapping of the placental edge is crucial to avoid placental injury and hemorrhage. A sterile intra-operative ultrasound is used to map for the placental borders. This is done while considering the position of the fetal head and neck to avoid excessive fetal manipulation after hysterotomy. The position of the hysterotomy is dictated by the placental location.

A low anterior placental site will preclude a low transverse hysterotomy and may necessitate a posterior approach for the hysterotomy. Special considerations are important in cases of severe polyhydramnios. Amnio-reduction in these cases is necessary to avoid underestimation of the proximity of the placental edge to the hysterotomy.

In order to adequately manipulate the fetus, it is sometimes indicated to decompress any accompanying fetal ascites or cystic mass. This can be achieved using a 20- or 22-gauge spinal needle under ultrasound guidance. In some instances, the use of amnio-infusion and fetal version before hysterotomy facilitate the exposure (12).

During EXIT procedures, hysterotomy is done using a specially designed uterine stapler (U.S. Surgical Corporation, Norwalk, Conn.) to decrease the incidence of bleeding (13). Following hysterotomy, maintenance of uterine volume is one of the important steps in an EXIT procedure. This is done to decrease the likelihood of uterine contraction and placental abruption and thus allow for a continuous maternal-fetal oxygen transfer.

Warm Ringer's lactate solution is infused after the hysterotomy to maintain the uterine volume and prevent cord compression. Limited exposure of the fetus during the EXIT procedure also helps in maintaining the uterine volume and fetal temperature. Only the head, neck and shoulders are exposed while keeping the remainder of the fetus and the cord intra-uterine.

The most important point in the management of the fetal airway during EXIT procedures is to be prepared for every contingency. One can never assume that the fetus will only require direct laryngoscopy and intubation, and so we have developed an airway algorithm.

	Airway algorithm to secure a fetal airway for neck masses at Cincinnati Children’s Hospital Medical Center, one of the partnering institutions of the Fetal Care Center of Cincinnati.

In addition to the basic instruments and set-up, the following items should be available on a separate airway table managed by a second scrub nurse: direct laryngoscopy supplies with Miller 0 and 00 blades, armoured endotracheal tubes (ETT) appropriate for the size of the fetus, endotracheal tube exchangers, 2.5 and 3.0 Fr feeding tubes for surfactant administration, 2.5 or 3.0 rigid bronchoscope, a flexible bronchoscope, and a major neck tray for formal tracheostomy or mass resection.

Direct laryngoscopy and endotracheal intubation should be the first option for securing a fetal airway during EXIT procedures.

	Bronchoscopy during an EXIT procedure to secure a fetal airway.

In cases where there is distortion of the normal anatomy, flexible and / or rigid bronchoscopy may be necessary to visualize and diagnose abnormal airway anatomy. Sometimes the glottis can be displaced cephalad above the level of the soft palate in which case, flexible bronchoscopy via the nares may be helpful. In other cases, mass effect may shift the glottis severely from its normal midline position.

An armoured endotracheal tube can be placed over the flexible bronchoscope or rigid lens and can be used to place the ETT beyond the level of obstruction. If this fails to secure an airway, then retrograde intubation becomes the next option in which a tracheotomy is performed through limited neck dissection. Using a Seldinger technique, an ETT exchanger is passed retrograde until seen in the oropharynx and the ETT passed antegrade over the ETT exchanger and the tracheotomy repaired.

In the case of large neck masses, sometimes traction, by an assistant, of the mass off the airway will allow an armoured ETT to be passed beyond the level of obstruction. If there is severe compression, release of the strap muscles will often allow an armoured ETT to pass where it could not be before release. Sometimes, airway control is still impossible even after all these techniques have been tried.

In these cases, reflection of the mass off the airway or resection of the mass to facilitate formal surgical tracheostomy may be necessary. Proper positioning of the tracheostomy is very important especially in cases of giant neck masses in which the trachea is pulled out of the chest by neck hyperextension. It is not uncommon to find the carina at the level of the thoracic inlet due to the opisthotonic position of the head caused by a neck mass. Care should be taken to place the tracheostomy tube no lower than the second – third tracheal rings.

After securing the airway, it is prudent to confirm the position of the ETT, or tracheostomy tube relative to the carina using flexible bronchoscopy. This is particularly important in cervical or mediastinal masses. Surfactant can then be administered if needed, by a feeding tube passed through the ETT, and then the fetus is ventilated by hand.

Finally, umbilical arterial and venous access catheters can be placed and then the cord is clamped. Coordination between the surgical team and the anesthesiologists is of paramount importance at this moment to ensure adequate return of the uterine tone and proper hemostasis. The newborn is taken to an adjoining operating room for either further resuscitation or to complete the resection of the neck mass. The stability of the infant should dictate whether this is done or the baby goes to the Neonatal Intensive Care Unit for further resuscitation and initial management.

Exit procedure for airway compromise

Reversal of tracheal occlusion

The EXIT procedure was developed to manage cases of congenital diaphragmatic hernia where tracheal clipping was done antenatally. These cases needed a systematic approach in which tracheal occlusion was reversed before the baby was delivered.

The EXIT procedure allowed time for neck dissection while the fetus was still on placental support to remove the clips, perform bronchoscopy to rule out airway injury, intubate the fetus and administer surfactant.

The lessons learned from this experience with the EXIT procedure allowed the application of this technique in various other scenarios especially those in which a prenatal diagnosis of airway compromise was made. This table outlines the current indications for EXIT procedure at The Fetal Care Center of Cincinnati:

Current Indications for EXIT Procedure at the Fetal Care Center of Cincinnati

• Reversal of Tracheal Occlusion
• • Following tracheal clip or endo-luminal balloon procedures
• Fetal Neck Masses
• • Cervical Teratoma
  • Hemangioma
  • Goiter
  • Neuroblastoma
• Lung Masses
• • Congenital Cystic Adenomatoid Malformation of the Lung (CCAM)
  • Bronchopulmonary sequestration (BPS)
• Mediastinal Mass
• • Teratoma
  • Lymphangioma
• EXIT to ECMO
• • CDH with Lung Head Ratio (LHR) <1.0, and Liver up
  • Congenital Heart Disease (CHD)
  • • HLHS with intact / restrictive atrial septum
    • Aortic Stenosis with intact/restrictive atrial septum
  • CHD + CDH, LHR <1.2
• EXIT-to-Separation
• Congenital High Airway Obstruction Syndrome (CHAOS)
• • Tracheal atresia
  • Laryngeal atresia

Giant neck masses

Fetuses with giant neck masses have significant distortion of their anatomy and pose a threat to securing the airway at birth. Airway obstruction at birth is life threatening and associated with a high mortality. In giant fetal neck masses these deaths are usually associated with a delay in obtaining an airway and inability to ventilate the neonate. This delay can result in hypoxia, acidosis and anoxic brain injury. The deaths from such anomalies are even more tragic because these infants are otherwise normal and would otherwise have a good outcome (14).

Recently, there has been an increase in the diagnosis of fetal airway structural malformations due to the advances and the widespread use of prenatal ultrasonography. This is strikingly evident in the setting of fetal airway obstruction. Fetal airway obstruction may be either due to extrinsic compression by a mass effect or due to intrinsic obstruction of the larynx or trachea.

A number of fetal neck masses have been reported to cause fetal airway obstruction (see below). The more common examples include giant cervical teratomas or lymphangiomas, and less commonly fetal goiter, hemangioma or others. The vast majority of cases of fetal airway obstruction are due to teratomas or lymphangiomas.

Adapted from Timothy M.Crombleholme and Craig T.Albanese: "The Fetus with Airway Obstruction" in Harrison, Evans, Adzick, Holzgreze (3rd): The unborn patient, the art and science of fetal therapy, chap 24. Philadelphia, PA, WB Saunders, 2001, pp 357-371.

Cervical lymphangiomas either present as isolated lymphangiomas that are diagnosed at birth in otherwise healthy infants, or those detected prenatally in the second trimester. Lymphangiomas diagnosed early in gestation appear to arise in the posterior triangle, have an associated chromosomal abnormality in 60% of the cases, have many structural anomalies and are associated with a high mortality.

In contrast, lymphangiomas diagnosed during the third trimester or postnatally are usually located in the anterior triangle, are rarely associated with chromosomal anomalies and have a lower mortality. The mortality associated with a posteriorly located cystic hygroma diagnosed prior to 30 weeks’ gestation is high because of the significant incidence of non-immune hydrops.

The natural history of prenatally diagnosed cystic hygroma appears to be dependent upon gestational age at diagnosis, location of the cystic hygroma and most importantly, whether or not there are associated chromosomal or structural abnormalities (15).

On the other hand, cervical teratoma is a rare tumor with approximately 150 congenital cases described (16). Teratomas are composed of tissues foreign to its anatomic site, with all three germ layers represented. Neural tissue is the most common histologic component, with cartilage and respiratory epithelium also observed.

Cervical teratoma is theorized to originate from either totipotential germ cells or result from abnormal development of a conjoined twin. Cervical teratomas are usually large and bulky typically ranging from 5 to 12cm in diameter.

Tumors greater than the size of the fetal head have also been reported. They can extend from the mastoid process and body of the mandible, superiorly displacing the ear, to the clavicle and sternal notch. Posteriorly, they can reach the anterior border of the trapezius. Teratomas can extend into the floor of the mouth or involve the tongue (epignathus) or into the mediastinum. Cervical teratoma may be associated with other congenital anomalies like:

• Chondrodystrophia fetalis
• Imperforate anus
• Hypoplastic left ventricle
• Trisomy 13
• Mandibular hypoplasia (17)

Polyhydramnios is present in up to 40% of the prenatally diagnosed cases and is more commonly observed in association with large tumors. In these cases, polyhydramnios is caused by the obstruction of the fetal esophagus.

The prenatal diagnosis of giant fetal neck masses was conventionally based on the use of ultrasonography. On prenatal ultrasonography, cystic hygromas are typically mutliloculated cystic masses with poorly defined borders that infiltrate the normal structures of the neck. This contrasts with the usually well-defined borders of cervical teratomas.

The differentiation of a cervical teratoma versus a lymphangioma is sometimes difficult due to the similarities in size, sonographic findings, clinical characteristics, location and gestational age at presentation. In addition, it is difficult to evaluate the airway and surrounding tissues of the neck solely by ultrasound.

Hubbard et al. described the first cases of giant neck masses evaluated by fetal magnetic resonance imaging (MRI). In this study, the authors concluded that the half-Fournier single-shot turbo spin-echo (HASTE) images provide the best anatomic definition of the fetus and neck mass.

	MRI picture in sagittal view demonstrating a large cervical teratoma. There is a 12X6cm heterogeneous mass compressing and displacing the fetal trachea.

In this study, fetal MRI provided a correct diagnosis of the tumor in each case, in addition MRI provided better detail about the size and position of the mass and its anatomic relationship to the airway compared to ultrasound (18).

The improved visualization of the relationship of the mass to the entire airway may help predict which patients are at the highest risk for airway obstruction, and thus the need for the EXIT strategy. There has been some concern about performing MRI on the developing fetus, but follow-up studies of prenatal MRI have not demonstrated any deleterious effects in humans (19). Thus, the current recommendation in the diagnosis of fetal neck masses is ultra-fast fetal MRI.

As fetuses with prenatally diagnosed fetal airway obstruction reach viability, they should be monitored closely for the development or progression of hydrops or cardiac decompensation. If the development or progression of hydrops is noted sonographically, open fetal surgery may be necessary to salvage the patient if less than 30 weeks gestation. If later in gestation, the fetus should be delivered by using the EXIT strategy.

Application of the EXIT procedure in the setting of giant fetal neck masses pose a number of important considerations that must be taken into account. The most pressing issue is the successful securing of a fetal airway. Although fetal neck masses can cause polyhydramnios and preterm labor, the most significant aspect of their management is treating a compromised airway at the time of delivery.

The timing of the EXIT is often dictated by severity of polyhydramnios and preterm labor. The mean gestational age of fetuses with neck masses undergoing EXIT procedure is 34 weeks. Airway compromise is a function of the location of the mass and distortion of the airway, not necessarily the absolute size of the neck mass.

As mentioned before, the surgeon must be prepared for every possible airway contingency. All the available modalities to secure the fetal airway are detailed under the description of the EXIT procedure, and are outlined in the algorithm in figure-1. Other important issues to consider when performing an EXIT procedure for giant neck masses include:

1. The possibility of wedging of the lungs in the apex of the chest as a result of the neck hyperextension. Despite the fact that a successful EXIT strategy can be applied in these cases, significant morbidity and mortality should be anticipated because of the associated lung hypoplasia.
2. The chance of the trachea being pulled up into the neck may lead to the underestimation of the site of tracheostomy leading to an inappropriately low tracheostomy site.
3. The occurrence of polyhydramnios as a result of esophageal compression, this may lead to underestimation of the proximity of the placental edge to the site of hysterotomy with increased risk of bleeding.
4. Some of the cases of fetal neck masses are caused by a cystic mass lesion. In such cases, decompression of the mass before the hysterotomy under ultrasonographic guidance will help in fashioning the hysterotomy and delivery of the fetal head and neck.

Based on our cumulative experience in the application of the EXIT procedure in different situations, we summarized a group of pitfalls and hard earned lessons in an attempt to provide guidance when applying the EXIT approach for management of a number of fetal conditions:

Congenital High Airway Obstruction Syndrome / CHAOS

Congenital high airway obstruction syndrome is a prenatally diagnosed clinical condition associated with hydrops in which near complete or complete intrinsic obstruction of the fetal airway prevents the egress of lung fluid from the tracheobronchial tree.

The incidence of CHAOS is rare, with only 52 cases reported. However, 22 of these cases have been reported since 1989, making the incidence of CHAOS difficult to determine (20). The true incidence may be higher because many of these cases die in utero or are still-born. There are multiple etiologies for the intrinsic obstruction of the airway in CHAOS including:

• Laryngeal atresia
• Laryngeal web
• Tracheal atresia
• Laryngeal cyst

Despite these multiple etiologies, the clinical presentation of these cases is the same: bilaterally enlarged echogenic lungs, dilated airways and flattened or inverted diaphragms with associated fetal ascites and nonimuune hydrops.

	MRI picture in sagittal view demonstrating CHAOS in a 26 weeks’ gestation. There is homogenous enlargement of both lungs with inversion of the diaphragm, and massive ascites.

Previous studies using a fetal lamb tracheal ligation model showed that the same effects of CHAOS could be replicated, and the investigators showed that reversal of tracheal occlusion can reverse the consequences of airway obstruction including capillary leak syndrome, respiratory distress syndrome, tracheobronchomalacia and diaphragmatic dysfunction (21).

Lim et al., reported a series describing the prenatal natural history of CHAOS may be less dismal than the previously thought, which suggested that CHAOS associated with nonimuune hydrops is uniformly fatal.

It is clear that in some cases, hydrops may completely resolve in the third trimester as a result of tracheo-laryngeal or tracheo-esophageal fistulization. It is crucial to perform a detailed malformation scan when the diagnosis of CHAOS is made to exclude any other additional malformations like:

• Absent radius
• Anophthalmia
• Cardiac anomalies
• Esophageal atresia
• Fraser syndrome
• Genitourinary anomalies

In cases of laryngeal atresia associated with malformations of the esophagus and trachea, including tracheo-esophageal fistula, allow decompression of the obstructed tracheobronchial tree. These fetuses do not develop the typical manifestations of CHAOS such as hydrops.

As the natural history of CHAOS is not completely understood, once diagnosed, they require, at least, close surveillance and in severe cases, the possibility of either fetal intervention to ameliorate the progression of the disease or an EXIT approach with tracheostomy should be considered.

The EXIT procedure has been successfully applied in the setting of CHAOS (22). It allows the adequate control of the fetal airway by surgical tracheostomy. These fetuses will require prolonged ventilation and even longer surgical airway control or definitive reconstruction of their airway. The optimal timing for airway reconstruction in CHAOS has not yet been defined.

Miscellaneous Indications for the Exit procedure

Exit-to-Extra-corporeal membrane oxygenation (ECMO) strategy

The EXIT procedure is also useful in fetuses with severe pulmonary or cardiac malformations in which separation from the utero-placental circulation will lead to immediate instability in the new born. In such cases an EXIT-to-ECMO strategy may be applied to secure the airway, and insert venous and arterial cannulas for ECMO while on placental support.

This approach will avoid any period of hypoxia or acidosis during neonatal resuscitation (Fig 6). We currently are offering EXIT-to-ECMO in cases of high risk CDH with lung-head circumference ratios (LHR) less than 1.0 with associated liver herniation placing them in the highest risk category for mortality and morbidity.

We also offer EXIT-to ECMO for cases of severe Aortic stenosis (AS) or HLHS when they are associated with restrictive atrial septum in which severe instability would be anticipated before the neonate can be transferred from the delivery room to the Catheterization lab.

EXIT-to-Resection

An EXIT-to-Resection strategy can also be employed in cases with large, high risk, chest masses such as congenital cystic adenomatoid malformation (CCAM) or mediastinal teratomas compromising the intrathoracic trachea. In these cases, the rationale for the EXIT procedure is to allow for the resection of the mass while on placental support (23); facilitating postnatal ventilation and venous return to the heart should ECMO be necessary for pulmonary hypoplasia.

EXIT-to-Separation strategy in Conjoined twins

Bouchard et al in 2002 reported the use of the EXIT procedure as a bridge to separation of a set of thoracoomphalopagus conjoined twins where one of the twins had a rudimentary heart with a single ventricle. It was anticipated that the twins would not survive for long postnatally as the twin's heart was already decompensating in utero. During the EXIT procedure, both twins were intubated, and an echocardiogram was performed to define shared vascular anatomy that was essential for immediate separation at birth.

Complications of the EXIT procedure

The EXIT procedure is associated with an increased potential risk of maternal bleeding due to uterine hypotonia induced by high concentrations of inhalational agents. The high levels of inhalational agents may also induce maternal hypotension. It is important to ensure the prompt return of uterine tone at the conclusion of the EXIT procedure to minimize maternal hemorrhage.

Although uterine atony remains a significant risk and there is the potential need for hysterectomy, the mean blood loss with EXIT procedures in our experience has been equivalent to that observed in C. Sections. We have only had to transfuse a single patient, early in our experience, in which polyhydramnios caused us to underestimate the proximity of the placenta to the hysterotomy.

In a review of their experience, the UCSF group reported that there was a slightly higher incidence of wound infection with EXIT procedures compared to C Sections. Although the EXIT procedure is specifically designed to optimize outcomes for the fetus, if not performed appropriately, there is also the potential for fetal complications. These are primarily related to failure to preserve uteroplacental gas exchange due to cord compression, placental abruption or loss of myometrial relaxation.

Conclusion

The EXIT procedure is an important tool in the management of prenatally diagnosed congenital malformations. Although it was originally described for the reversal of tracheal occlusion done in cases of severe congenital diaphragmatic hernias, the period of uteroplacental bypass it affords can be used in various other settings where cardio-pulmonary compromise is anticipated. The EXIT procedure provides the surgeon with the luxury of transforming a potentially fatal neonatal emergency to a controlled environment to insure a better outcome.

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