The EXIT Procedure
Shane Pahlavan, M.D.
September 18, 2008

WG is a 28-week preemie found to have polyhydramnios, an inverted diaphragm and upper airway obstruction on ultrasound.  Here is an example of the ultrasound.  This arrow denotes the inverted diaphragm.  The head of the baby, for reference, is to the right.  These are her lungs, which are noted to be enlarged. This is the abdomen here, which is noted to have some ascites and air fluid levels.  Prenatal course for the mother and the fetus was uneventful to that point.  This ultrasound raised a concern over possible CHAOS syndrome, or congenital high airway obstruction syndrome, with impending airway obstruction upon delivery.  C-section was scheduled at 37 weeks and EXIT procedure or Ex-Utero Intrapartum Treatment was planned.  The mother was induced at 37 weeks and caesarean section was performed.   The head, shoulders, thorax and one arm was delivered.  Monitors were applied for close monitoring.  Direct laryngoscopy and bronchoscopy was performed. Here is an endoscopic picture of the supraglottis and the vocal cords, which were noted to be normal on examination.   These other two pictures show, as you pass the bronchoscope through the glottis itself and then the subglottis, the upper trachea ended in a proximal blind pouch.  Diagnosis of CHAOS was confirmed, due to the subglottic and upper tracheal atresia.  Tracheostomy was performed and the airway was secured at that time.  The umbilical cord was clamped and then cut.  APGARS for the child were both 4 and 4 at 1 and at 5 minutes, respectively. The patient was transferred to the Neonatal ICU. 

What is CHAOS syndrome? CHAOS is congenital high airway obstruction syndrome that is associated with hydrops with near complete or complete intrinsic obstruction of the fetal airway that prevents egress of lung fluid from the tracheal bronchial tree. This would lead to enlarged hypoechoic lungs as well as dilation of the entire tracheobronchial tree and ascites or polyhydramnios.  Etiologies include laryngeal atresia or laryngeal web, tracheal atresia, and laryngeal cyst.  It is thought embryologically to be due to failure of epithelial growth and recannulization in the vestibule and subglottic regions during the tenth week of embryogenesis. 

The clinical presentation, as I have mentioned, showed bilaterally enlarged lungs, dilated tracheobronchial tree and dilated airways.  A flattened or inverted diaphragm, which can be seen on ultrasound, is present with a large abdomen and associated ascites or hydrops.  Infants with laryngeal atresia initially appear healthy at birth, but become cyanotic once the umbilical cord is clamped secondary to inability to ventilate the lungs. Performing emergency tracheostomy soon after delivery is necessary for survival because the impenetrable length cannot be intubated.  So, it is important to identify these patients preoperatively to avoid this situation after birth when the umbilical cord is cut. 

There are some considerations with the pediatric airway to keep in mind.  The epiglottis of the pediatric airway is floppier and more U-shaped. The airway is higher and more anterior.  The cricoid ring is the narrowest portion of the pediatric airway and the trachea is more flexible. The larynx and trachea are significantly smaller in diameter and length.  Pediatric patients are ill-prepared to tolerate even 1 millimeter of edema or narrowing.  The tongue occupies almost the entire mouth in the infant airway.  So, the infant is an obligate nasal breather up until almost 5 months usually. 

The diagnosis of CHAOS syndrome can also be made by MRI.  The lungs are noted to be enlarged and the tracheobronchial tree is dilated. The abdomen shows significant ascites.  This is another image of an ultrasound showing inverted diaphragms. The lungs are hyperinflated and enlarged, pushing the diaphragm down with a large abdomen and air-fluid level.  The picture on the right is a fetal MRI with CHAOS with laryngeal atresia.  The proximal upper airway is attenuated and then is present again distally. 

This is a post-operative PA and lateral chest x-ray showing the enlarged lungs and you can note the extensive flattening and almost inversion here of the diaphragm.  This is very suggestive of the CHAOS.

What is the EXIT procedure?  It is Ex-Utero Interpartum Treatment.  It was designed initially for repair of tracheal occlusion after clip placement in patients with severe congenital diaphragmatic hernias.  Tracheal clips were placed during fetal surgery and the procedure was used to remove those clips prior to birthing the patient.  It insured an optimal, controlled environment, on uteroplacental bypass while the tracheal occlusion was reversed at delivery.  This provided a prolonged, stable fetal hemodynamic environment with preservation of placental gas exchange.  Now, as seen in current literature, it has proven some utility with fetal neck masses and airway obstruction. 

So, the question comes up, isn’t it merely a C-section?  So, let us talk about the goals of a C-section versus an EXIT procedure.  A caesarean section’s goals are multiple.  It is to maximize uterine tone to prevent post-partum hemorrhage and minimizing the transplacental diffusion of inhalational anesthetic agent to avoid depression in the neonate.  However, the EXIT procedure goals are quite different.  It is to achieve a state of uterine hypotonia instead of maximizing uterine tone.  One must achieve a state of uterine hypotonia to maintain uteroplacental circulation. The goal is to preserve uterine volume to prevent placental abruption.  A deep plane of maternal anesthesia is maintained with normal maternal blood pressures.  Lastly, it is paramount to achieve a surgical level of fetal anesthesia without cardiac depression. 

How is it performed?  The placenta is mapped prior to the hysterotomy by ultrasound to avoid injuring the placenta during the hysterotomy incision.  Hysterotomy is performed, and partial delivery of the fetus is done while maintaining placental gas exchange.  The umbilical cord is left intact at this point.  Monitors are applied for fetal monitoring and oxygen saturation; oftentimes an echocardiogram is used to monitor the fetal heart rate.  The airway is secured via direct laryngoscopy or bronchoscopy so the tracheotomy can be placed.  This picture shows partial delivery of the fetus.  The head, thorax and at least one arm are delivered for monitoring.  Interventions can then be undertaken. 

What anesthetic concerns should we know about with the EXIT procedure?  The mother is induced with rapid sequence of thiopental, succinylcholine, and fentanyl given IV followed immediately by intubation.  The anesthesia is maintained with 0.5 MAC or minimum alveolar concentration with desflurane or isoflourine and adjusted to 2.0 MAC prior to incision to decrease uterine tone.  As I mentioned, one of the key concepts of EXIT procedure is uterine hypotonia to allow for a continued uteroplacental gas exchange.  In a normal c-section, the uterine tone would be increased to decrease further blood loss.  You have to keep the patient fairly sedated under 2.0 MAC.  For fetal anesthesia, however, it is important to minimize decrease placental transfer of any maternal anesthetics administered.  

What are the indications for use of EXIT procedure?  As I have mentioned previously, reversal of tracheal occlusion is the most common indication historically following tracheal clip for endoluminal balloon procedures for congenital diaphragmatic hernias.  Some new indications that have come out within the past ten years including fetal neck masses, cervical teratoma, hemangioma, goiters and neuroblastoma.  Some lung masses have been shown some utility in using the EXIT procedure including C-CAM or congenital cystic adenomatoid malformation of the lung as well as bronchopulmonary sequestration.  Mediastinal masses including teratoma, lymphangioma, some of the EXIT-to-ECMO procedures for the children with congenital heart diseases as well as EXIT separation procedures for conjoined twins have been reported.  Patients with CHAOS syndrome, as in our case presentation, with tracheal or laryngeal atresia provide yet another indication.

In 2006, Otteson et al in Archives of Otolaryngology reported a case series of three successful EXIT procedures performed at their institution.  They introduced severe micronathia to indications of EXIT procedures. The picture to the right shows a patient with severe micrognathia that was delivered via an EXIT procedure and a tracheotomy tube was placed to secure the airway.  They demonstrated the feasibility of performing the EXIT procedure as early at 26 weeks of gestation.  This does not take into account the fact of the lack or deficiency or other pulmonary surfactant.  But, they did report that it was safe to perform the procedure that early. This is a patient from their study with a large lymphatic malformation that they performed an EXIT procedure on and were able to successfully intubate the patient orally. 

Their conclusion was that the role of the pediatric otolaryngologist, with their expertise in comprehensive management of the pediatric airway, will become increasingly involved with the EXIT procedure.  Here are two other patients from their study. This is a picture of a fetus with a large cervical teratoma undergoing a tracheostomy.

Bouchard, in 2002, published a review article in the Journal of Pediatric Surgery. This was a retrospective chart review of all consecutive EXIT procedures at their institution since 1996.  Their study included 31 patients with an average maternal age of 29 and average gestational age of 34 weeks. They studied the duration of uteroplacental bypass, which they defined as a uterine incision or hysterotomy incision to umbilical cord clamping. In their study, no fetus experienced hemodynamic instability, except for one instance of reversible bradycardia from a fetus with umbilical cord compression.  A single death occurred as a result of inability to secure the airway secondary to extensive involvement by lymphangioma.  They also reported that maternal complications were minimal.  Here are some pictures from their study.  This patient is undergoing a direct laryngoscopy.  This is another patient with a large teratoma and this is the same patient’s MRI revealing enlarged lungs, dilated tracheal bronchial tree, ascites, and a floating intestine and liver.  This is a chart from Bouchard’s study with documented indications and gestational age at the time of the EXIT procedure.  This paper describes 31 total procedures with 13 of the 31 performed for reversal of tracheal occlusion in patients with congenital diaphragmatic hernia.  They had a large number of giant fetal neck masses that they performed the EXIT procedure on as well as many other indications: EXIT-to-ECMO, resection of C-CAM, unilateral pulmonary agenesis, bridge between conjoined twins, and just one CHAOS patient.  Of note, 34 weeks was their average gestation age with no significant difference noted.  You can see 26 out of the 31 indications for the EXIT procedure were either for reversal of tracheal occlusion or for giant fetal neck masses, and just one CHAOS patient. 

The average duration of uteroplacental gas exchange for the EXIT procedure was found to be 30.3 minutes. The surgeons, therefore, have quite a bit of time to perform airway interventions to safely ventilate the patient.  Their single CHAOS patient required 25 minutes to secure the airway and discontinue uteroplacental gas exchange. 

Hirose et al in 2004 published a retrospective review in the Journal of Pediatric Surgery describing patients undergoing the EXIT procedure at their institution, UC San Francisco, from 1993 to 2003.  They had 52 patients, and multiple outcome measures including gestational age, excess birth weight, maternal blood loss, survival and operative time.  This is chart from their study detailing their outcomes data.  Out of the 52 patients in their review, 45 underwent the EXIT procedure to reverse the tracheal clipping, 5 for neck masses and 2 CHAOS patients.  Their survivor statistics were quite low when compared to the other studies.  Fifty-two percent of their patients survived.  All the patients that did not survive had severe congenital diaphragmatic hernias.  Female to male ratio was 1:2.  Their gestational age was roughly 32 weeks and birth weights average about 1900 grams, which correlates to some of the previous studies.  Maternal blood loss was 970 ml +/-510 ml.  A controversial topic in the current literature with regard to the EXIT procedure centers around maternal blood loss.  Many physicians and health care professionals were concerned that this procedure may increase blood loss to the mother; however, most studies have shown less than a 1,000-ml blood loss. This amount is comparable to the acceptable blood loss seen in a routine caesarean section, which most sources quote between 500 and 1,000 ml blood loss. Therefore, there is no increased morbidity to the mother in most cases. 

The EXIT procedures can be performed with minimal maternal morbidity with good outcome.  This is an excellent strategy for establishing an airway in a controlled manner and allows for longer procedures on placental support allowing for definitive management.  They conclude that EXIT procedures have evolved from an adjunct to fetal surgery to a life saving procedure with fetuses with airway compromised at birth. 

Rahbar et al in 2005 reported on a retrospective case series in Archives of Otolaryngology describing some the technological advances in prenatal ultrasonography and MRI in the diagnosis and management of fetal airway obstruction caused by cervical teratoma or lymphatic malformation. As I mentioned previously, it is paramount to diagnosis these children pre-operatively as there may be no concern over the child’s airway until the umbilical cord is clamped.  These are a few pictures from this study.  The MRI reveals a large heterogeneous complex oral pharyngeal and neck mass.  Note the tongue protrusion out of the oral cavity due to displacement by the mass as well as tracheal deviation.    

To follow-up on our case presentation: this is WG, he is now 9 months old.  He underwent a tracheal reconstruction with primary anastamosis on September  5th. He underwent direct laryngoscopy and bronchoscopy with successful extubation on September 17th.  Here is a picture of him from last night.  He is currently stable and recovering in the Neo-natal ICU at Texas Children’s Hospital. 

In summary, the EXIT procedure was designed and refined initially for reversal of tracheal occlusion in fetuses that underwent fetal tracheal clip application for severe congenital diaphragmatic hernias.  It does require multi-disciplinary approach and meticulous pre-operative planning.  The treatment team must take into account anesthetic treatment of both the mother and the fetus.  A period of sustained utero-placental gas exchange is required to partially deliver the baby, expose the trachea and reverse the airway obstruction.  Maintaining prolonged uterine relaxation with deep inhalation anesthesia leading to preserved utero-placental blood flow and gas exchange is the hallmark of the EXIT procedure. This gives the surgeon time to establish an airway, either by intubation or by tracheotomy placement.  The use of this procedure can be expanded to care for fetuses with giant neck masses at delivery.  Outcomes have been good with majority of infants surviving this procedure with excellent short and long-term maternal outcomes. 

EXIT procedures are a valuable adjunct to surgical armamentarium available to treat various fetal diseases. Improved prenatal imaging will result in an increase in diagnostic capabilities.  The field of pediatric otolaryngology will increasingly be faced with new challenges in diagnosis and management of fetal airway abnormalities. 

This is a treatment algorithm that I think kind of helps summarize everything together.  During the EXIT procedure, you would first attempt oral tracheal intubation.  If this is successful, you divide the umbilical cord and the EXIT procedure is complete.  If oral tracheal intubation is unsuccessful, you have to raise the question: Is the airway thought to be technically accessible transorally?  If it is, you would attempt a bronchoscopy.  If successful, and the mother is stable, you could then perform a tracheotomy over the bronchoscope and then divide the umbilical cord.  If the mother is not stable, you would have to terminate the EXIT procedure, divide the umbilical cord, and perform a tracheotomy over the bronchoscope. If an attempt of oral tracheal intubation is not going to be an option based on pre-operative imaging, as in our patient with some type of atresia or laryngeal or trachea atresia, you would go ahead and perform a tracheotomy on placental support and then divide the umbilical cord.  This was the scenario in the patient from our case presentation.  If the tracheotomy is unsuccessful secondary to a large neck mass and tracheal deviation, you can excise the mass or decompress the cyst to allow for tracheotomy.

Case Presentation

Baby Boy Graves is a 28-week preemie found to have polyhydramnios, inverted diaphragms, and upper airway obstruction on routine prenatal ultrasound.  The prenatal course was uneventful to that point.  A diagnosis of CHAOS (Congenital High Airway Obstruction Syndrome) was suspected with an impending airway obstruction upon delivery.  The mother was scheduled Cesarean section at 37 weeks gestation. An EXIT (Ex-Utero Intrapartum Treatment) procedure was planned at delivery. The mother was induced and Cesarean section performed.  The head, shoulders, thorax, and one arm of the fetus were delivered.  Direct laryngoscopy and bronchoscopy was immediately performed. The supraglottis and vocal cords appeared normal. However, the proximal cervical trachea was noted to end in a blind pouch and the bronchoscope was unable to be passed distally.A diagnosis of CHAOS (Congenital High Airway Obstruction Syndrome) was confirmed due to subglottic/tracheal atresia and a tracheostomy was performed. After the airway was secured, the umbilical cord was clamped and cut.  Apgar scores were 4 and 4 at 1 and 5 minutes.  The patient was transferred to the Neonatal ICU in stable condition.  The patient is now 8 months old and was taken for tracheal reconstruction with primary anastomosis on 9/5/08.  He is currently stable and recovering in the Neonatal ICU at Texas Children’s Hospital.

Bibliography

Bouchard S. The EXIT Procedure: Experience and Outcome in 31 Cases. J Pediatr Surg 2002;37:418-426.

DeCou J. Successful ex utero intrapartum treatment (EXIT) procedure for congential high airway obstruction syndrome (CHAOS) owing to laryngeal atresia. J Pediatr Surg 1998;33:1563-1565.

Goldman N. Endoscopic appearance of laryngeal atresia. Otolaryngol Head Neck Surg 1997;117:137.

Hirose S. The ex utero intrapartum treatment procedure: looking back at the EXIT. J  Pediatr Surg 2004;39:375-380.

Isaacson G, Friedman E. Congenital anomalies of the larynx. Up To Date 2008; May.

Kuwashima S. MR imaging appearance of laryngeal atresia (congenital high airway obstruction syndrome): unique course in a fetus. Pediatr Radiol 2008;38:344-347.

Mychaliska G. Operating on placental support: the ex utero intrapartum treatment procedure. J Pediatr Surg 1997;32:227-231.

Otteson T. The ex utero intrapartum treatment (EXIT) pProcedure. New challenges. Arch Otolaryngol Head Neck Surg 2006;132:686-689.

Rahbah R. Fetal surgery in otolaryngology. A new era in the diagnosis and management of fetal airway obstruction because of advances in prenatal imaging. Arch Otolaryngol Head Neck Surg 2005;131:393-398.