Seminars in Pediatric Surgery (2006) 15, 107-115

The EXIT procedure: principles, pitfalls, and progress

Ahmad Marwan, MD, Timothy M. Crombleholme, MD

From the Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic, and Fetal Surgery, Cincinnati
Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio.

INDEX WORDS Although performing procedures on a fetus before severing the umbilical cord has previously been
Ex utero intrapartum reported, the principles of the ex utero intrapartum treatment (EXIT) procedure were first fully
(EXIT) procedure; developed for reversing tracheal occlusion in fetuses with severe congenital diaphragmatic hernia. The
Cervical teratoma; EXIT procedure offers the advantage of insuring uteroplacental gas exchange while on placental
Congenital high support. The lessons learned in the development of the principles that underlie the EXIT procedure have
airway obstruction improved outcomes when applied in other conditions, most notably in cases of airway obstruction. The
syndrome (CHAOS); range of indications for the EXIT procedure has expanded and currently includes giant fetal neck
Uteroplacental gas masses, lung or mediastinal tumors, congenital high airway obstruction syndrome, and EXIT to ECMO
exchange; (extracorporeal membrane oxygenation), among others. This review summarizes the underlying prin-
Fetal surgery ciples of the EXIT procedure, the expanding indications for its use, the pitfalls of management, and the
progress that has been made in its successful application.
© 2006 Elsevier Inc. All rights reserved.

Advances in prenatal diagnosis of fetal congenital
malformations, in particular tumors or malformations in-
volving the fetal airway, have facilitated the development
of a strategy to convert potentially catastrophic events
during delivery to a controlled procedure. Lesions that
compromise the fetal airway constitute an immediate
threat to the newborn airway, with the risk of hypoxia,
ischemic brain injury, and/or death. In the past, numerous
case reports described intubation and bronchoscopy be-
fore severing the umbilical cord in patients with such
lesions.1 However, it was recognized that preserving
uteroplacental gas exchange required more than main-
taining the umbilical cord intact. Skarsgard and cowork-
ers described operating on placental support (referred to
as the OOPS procedure) in the treatment of a fetus with
anticipated airway obstruction.2 In these reports, intra-
Address reprint requests and correspondence: Timothy M. Cromble-
holme, MD, The Fetal Care Center of Cincinnati, Division of Pediatric Gen-
eral, Thoracic, and Fetal Surgery, Cincinnati Children’s Hospital Medical
Center, 3333 Burnet Ave MLC 2023, Cincinnati, OH 45229-3039.
E-mail: Timothy.Crombleholme@cchmc.org.
partum laryngoscopy or bronchoscopy during cesarean
section or vaginal delivery before placental separation
did not assure that uteroplacental circulation would be
maintained. In the OOPS procedure, no attempt was
made to prevent normal uterine contraction during the
procedure,3 and in some cases, the fetus was removed
from the uterus to instrument the airway; this resulted in
rapid loss of uterine volume. In both of these instances,
cessation of uteroplacental circulation would be ex-
pected. In contrast, the central principle of the EXIT
procedure is controlled uterine hypotonia to preserve the
uteroplacental circulation. Subsequently, the ex utero in-
trapartum technique (EXIT) procedure was described for
reversal of tracheal occlusion in fetuses with severe con-
genital diaphragmatic hernia (CDH).4 These cases re-
quired neck exploration for the removal of the tracheal
clips, with maintenance of uteroplacental blood flow until
the fetal airway was secured by endotracheal intubation.
Experience with the EXIT technique demonstrated fetal
and maternal hemodynamic stability and soon led to
expanded indications for its use. The indications have
broadened to include giant fetal neck masses, fetal me-

1055-8586/$ -see front matter © 2006 Elsevier Inc. All rights reserved.
doi:10.1053/j.sempedsurg.2006.02.008
108
diastinal, or lung masses, such as congenital cystic ad-
enomatoid 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. The goals during the latter pro-
cedure are to: (1) maximize the uterine tone to prevent
postpartum hemorrhage; and (2) minimize the transplacen-
tal diffusion of inhalational anesthetic agents to avoid neo-
natal depression (if performed under general anesthesia). In
contrast, the goals during the EXIT procedure are to: (1)
achieve a state of uterine hypotonia so to maintain the
uteroplacental circulation using deep general anesthesia; (2)
preserve uterine volume so to prevent placental abruption;
(3) reach a deep plane of maternal anesthesia but maintain
normal maternal blood pressure; and (4) achieve a surgical
level of fetal anesthesia without cardiac depression. In ad-
dition, the EXIT procedure requires synchronized team
work involving multiple disciplines, including at least one
or two pediatric surgeons or a pediatric otolaryngologist, a
maternal–fetal medicine specialist or obstetrician, an echo-
cardiographer, a neonatologist, two anesthesiologists, two
circulating nurses, and two scrub nurses.
Maternal anesthesia considerations
Unlike standard obstetric anesthetic practice in which re-
gional anesthesia is the rule, general anesthesia is the tech-
nique of choice for patients undergoing the EXIT procedure.
As with any fetal surgical procedure, the EXIT procedure
involves the treatment of two patients: the mother and her
baby. For this reason, we usually have one anesthesiologist
for the mother and another for the baby. There are a number
of maternal and fetal anesthesia considerations that must be
managed. 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 pregnan-
cy-related reduction of lower esophageal sphincter pressure,
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 hy-
potension, decreased uterine artery perfusion, and thus fetal
hypoxia. It is therefore important to position 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 a lower hematocrit and an increase in peripheral venous
capacity. Pregnancy also affects pulmonary function, with a
decrease in functional residual capacity that puts the mother
at an increased risk for hypoxia. For these reasons, maternal
anesthesia is induced through a rapid-sequence technique
Seminars in Pediatric Surgery, Vol 15, No 2, May 2006
using a combination of thiopental (5 mg/kg), succinylcho-
line (2 mg/kg), and fentanyl (1-2 ␮g/kg) administered in-
travenously. This is followed by immediate endotracheal
intubation. Paralysis is maintained using intravenous vecu-
ronium titrated by peripheral nerve stimulation.
Fetal anesthesia considerations
Support of the fetus during the EXIT procedure depends
entirely on the preservation of uteroplacental gas exchange.
Both uterine and umbilical artery blood flow influence fetal
oxygenation. Uterine artery blood flow is affected by ma-
ternal systemic blood pressure and myometrial tone. Vola-
tile 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 Maintenance of
maternal blood pressure within 10% of baseline is therefore
critical for adequate fetal oxygenation during the EXIT
procedure. Maintenance of maternal blood pressure is
achieved using ephedrine to counterbalance the hypotensive
effects of the high concentrations of inhalational agents
used in EXIT procedures. Ephedrine acts selectively on
peripheral vascular resistance and sparing placental circu-
lation.6 Uteroplacental gas exchange is also dependent on
umbilical artery blood flow, which is influenced by fetal
cardiac output and placental vascular resistance. Preserva-
tion of fetal cardiac output is thus important in maintaining
fetal oxygenation.
The cardiovascular physiology of the fetus is different
from that of full-term neonates in that the cardiac output is
more dependent on heart rate rather than on stroke volume.
In addition, 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 redistribution in
response to stress. This preserves oxygenation for the brain
at the expense of the rest of the body. In addition to the
peculiar characteristics of fetal physiology, inhalational an-
esthetics also cause a direct fetal myocardial depression,
vasodilatation, and changes in arteriovenous shunting, all of
which can lead to fetal hemodynamic instability.7 These
physiologic differences and responses to anesthetic agents
require continuous fetal monitoring to ensure uncompro-
mised uteroplacental gas exchange and fetal well being.
The inhalational anesthetic regime used during the EXIT
procedure passes through two different stages. Anesthesia is
at first maintained with 0.5 MAC (minimal alveolar con-
centration) of desflurane, isoflurane, or sevoflurane in oxy-
gen, and is then increased to 2 MAC before maternal inci-
sion. It is subsequently increased as needed before
hysterotomy to achieve the 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 indometha-
Marwan and Crombleholme EXIT Procedure
cin, terbutaline, or nitroglycerine. Indomethacin may also
prevent prostaglandin-mediated increases in placental resis-
tance independent of its effects on uterine tone.8 Mainte-
nance of uterine volume is also important to prevent uterine
contraction. This is accomplished by preventing the fetus
from completely delivering and by the use of amnioinfusion
with warm Ringer’s lactate solution administered via a rapid
infuser to prevent cord compression.
The second critical stage of the anesthetic technique
comes just before clamping of the cord and ending the EXIT
procedure. During this stage, coordination between the sur-
gical 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. This is followed by administration
of oxytocin 20 units in 500 mL of normal saline intrave-
nously as a bolus followed by 10 units in a 1000-mL drip
titrated to enhance uterine contraction. If required, further
measures are taken to decrease the risk of uterine atony.
These measures include uterine massage and administration
of 0.25 mg Methergine and 250 ␮g carboprost (F2-alpha
prostaglandin) via intramuscular or intravenous injection.
After skin closure, the inhalational anesthetic is discontin-
ued and 100% oxygen is administered. Maternal paralysis is
reversed by the use of glycopyrrolate (10 ␮g/kg) and
neostigmine (0.7mg/kg), and the patient is extubated after
spontaneous breathing is observed.9
Fetal anesthesia is provided primarily through the trans-
placental passage of the volatile anesthetics. However, this
takes about an hour to reach 70% of the maternal levels. As
such, before fetal incision, a cocktail comprising 10 to 20
␮g/kg fentanyl, 20 ␮g/kg atropine, and 0.2 mg/kg vecuro-
nium is administered intramuscularly to supplement anes-
thesia and provide for postoperative analgesia.
Maternal and fetal monitoring
Close maternal and fetal monitoring during the EXIT pro-
cedure aim at the early recognition and management of
problems as they arise. Maternal monitoring includes inva-
sive arterial blood pressure monitoring (arterial line) to
recognize possible maternal hypotension that will jeopar-
dize fetal oxygen transport, continuous electrocardiography,
pulse oximetry, and end-tidal CO2 monitoring.
Continuous fetal monitoring is of paramount importance
during the EXIT procedure. Fetal arterial saturation is mon-
itored by a reflectance pulse oximeter placed on the fetal
hand and wrapped with foil to decrease ambient light ex-
posure.10 Normal fetal arterial saturation is 60% to 70%,
although values greater than 40% represent adequate fetal
oxygenation. Continuous intraoperative fetal echocardiog-
raphy is also used to monitor fetal cardiovascular func-
tion.11 The use of fetal echocardiography helps to identify
early problems such as decreased filling, fetal bradycardia,
decreased myocardial contractility, ductal constriction, and
109
Figure 1 An intraoperative view during an EXIT procedure
demonstrating continuous fetal monitoring using a sterile echocar-
diography, reflectance pulse oximetry, and IV access lines. (Color
version of the figure is available online.)
atrioventricular valve incompetence (Figure 1). 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 performing the EXIT procedure. The
incision of choice is usually a low transverse abdominal
incision unless anterior position of the placenta necessitates
a posterior hysterotomy. In the latter case, a midline lapa-
rotomy is required. After laparotomy, the uterus is exam-
ined for adequacy of myometrial relaxation, and concentra-
tion of inhalational agents is adjusted as necessary. Before
fashioning the hysterotomy, precise sonographic mapping
of the placental edge is crucial to avoid placental injury and
hemorrhage. A sterile intraoperative ultrasound (US) is used
to map the placental borders. This is performed while con-
sidering the position of the fetal head and neck to avoid
excessive fetal manipulation after hysterotomy. The posi-
tion of the hysterotomy is dictated by the placental location.
A low anterior placental site precludes a low transverse
hysterotomy and may necessitate a posterior approach for
the hysterotomy. Special considerations are important in
cases of severe polyhydramnios. Amnioreduction in these
cases is necessary to avoid underestimation of the proximity
of the placental edge to the hysterotomy. To adequately
manipulate the fetus, it is sometimes necessary to decom-
press any accompanying fetal ascites or cystic mass. This
can be achieved by using a 20- or 22-gauge spinal needle
110
Airway Algorithm for Neck Masses at CCHMC
Direct Laryngoscopy
Intubation
Yes No
EXIT complete Distorted larynx Compressed trachea
Rigid bronchoscopy
Successful tracheoscopy
Yes No
Intubation with armored Elevate mass off the airway
ETT
No
Yes
Open neck, Release strap muscles
No
Tracheostomy with retrograde intubation
over *ETT exchanger
Airway secured, position
confirmed by flexible bronchoscopy Yes
Formal Tracheostomy
EXIT COMPLETE
*ETT, endotracheal tube
Figure 2 Airway algorithm to secure a fetal airway for neck
masses at Cincinnati Children’s Hospital. (Color version of figure
is available online.)
under US guidance. In some instances, the use of amnioin-
fusion and fetal version before hysterotomy facilitate the
exposure.12 During EXIT procedures, hysterotomy is per-
formed using a specially designed uterine stapler (U.S.
Surgical Corporation, Norwalk, CT) to decrease the inci-
dence of bleeding.13 Following hysterotomy, maintenance
of uterine volume is one of the most important steps in an
EXIT procedure. This is done to decrease the likelihood of
uterine contraction and placental abruption, thus maintain-
ing continuous maternal–fetal oxygen transfer. Warm Ring-
er’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 tem-
perature. Only the head, neck, and shoulders are exposed
while keeping the remainder of the fetus and the cord
intrauterine.
The most important aspect of fetal airway management
during an EXIT procedure is preparedness for every con-
tingency. In that one can never assume that the fetus will
only require direct laryngoscopy and intubation, we have
developed an airway algorithm (Figure 2).
In addition to the basic instruments and set-up, the fol-
lowing items should be available on a separate airway table
Seminars in Pediatric Surgery, Vol 15, No 2, May 2006
managed by a second scrub nurse: direct laryngoscopy sup-
plies with Miller 0 and 00 blades, armored endotracheal
tubes (ETT) appropriate for the size of the fetus, endotra-
cheal 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 (Figure 3). In cases in which there is distortion
of the normal anatomy, flexible and/or rigid bronchoscopy
may be necessary to visualize and diagnose abnormal air-
way anatomy. The glottis is sometimes displaced cephalad
above the level of the soft palate; in such cases, flexible
bronchoscopy via the nares may be helpful. In other cases,
mass effect may shift the glottis severely from its normal
midline position. An armored 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 per-
formed through limited neck dissection. Using a Seldinger
Airway technique, an ETT exchanger is passed retrograde until seen
No
in the oropharynx. The ETT is passed antegrade over the
ETT exchanger and the tracheotomy repaired. In the case of
large neck masses, traction by an assistant may lift the mass
off the airway. This permits an armored ETT to be passed
beyond the level of obstruction. If there is severe compres-
sion, release of the strap muscles may be required to permit
passage of an armored ETT beyond the area of airway
obstruction. Airway control is sometimes impossible even
after all these techniques have been attempted. 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 ex-
tremely 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
Figure 3 Bronchoscopy during an EXIT procedure to secure a
fetal airway. (Color version of figure is available online.)
Marwan and Crombleholme EXIT Procedure 111

Table 1 Current indications for the EXIT procedure at the

tal support to remove the clips, perform bronchoscopy to
Fetal Care Center of Cincinnati rule out airway injury, intubate the fetus, and administer
surfactant. The lessons learned from this experience allowed
Reversal of Tracheal Occlusion the application of this technique in various other clinical
Following tracheal clip or endoluminal balloon procedures scenarios, especially those in which a prenatal diagnosis of
Fetal Neck Masses
Cervical teratoma airway compromise was made. Table 1 outlines the current
Hemangioma indications for use of the EXIT procedure at The Fetal Care
Goiter Center of Cincinnati.
Neuroblastoma
Lung Masses
Congenital cystic adenomatoid malformation (CCAM)
Bronchopulmonary sequestration (BPS)
Mediastinal Mass Giant neck masses
Teratoma
Lymphangioma Fetuses with giant neck masses have significant distortion of
EXIT to ECMO their anatomy and pose a threat to securing the airway at
CDH with lung/head ratio (LHR) ⬍1.0, and liver up birth. Airway obstruction at birth is life-threatening and
Congenital heart disease (CHD)
Hypoplastic left heart syndrome (HLHS) with intact/
associated with a high mortality. Deaths are usually associ-
restrictive atrial septum ated with a delay in obtaining an airway and inability to
Aortic stenosis with intact/restrictive atrial septum ventilate the neonate. This delay can result in hypoxia,
CHD ⫹ CDH, LHR ⬍1.2 acidosis, and anoxic brain injury. Deaths from such anom-
EXIT-to-Separation alies are even more tragic in that these infants are otherwise
CHAOS normal and would otherwise have a good outcome.14
Tracheal atresia
Laryngeal atresia Due to technical advances and the widespread use of
prenatal US, there has been an increase in the diagnosis of
fetal airway structural malformations. This is strikingly ev-
ident in the setting of fetal airway obstruction. Fetal airway
the head caused by a neck mass. Care should be taken to obstruction may be due either to extrinsic compression by a
place the tracheostomy tube no lower than the second to
third tracheal rings.
After securing the airway, it is prudent to confirm the Table 2 Differential diagnosis of fetal airway obstruction
position of the ETT or tracheostomy tube relative to the
carina using flexible bronchoscopy. This is particularly im- Causes of extrinsic obstruction
Cervical teratoma
portant in patients with cervical or mediastinal masses. If
Congenital goiter
required, surfactant can then be administered by a feeding Solid thyroid tumors
tube passed through the ETT. The fetus is then ventilated by Thyroid cyst or thyroglossal duct cyst
hand. Finally, umbilical arterial and venous access catheters Branchial cleft cyst
can be placed and the cord clamped. Coordination between Neuroblastoma
Hamartoma
the surgical team and the anesthesiologists is of paramount
Hemangioma
importance at this moment to ensure adequate return of the Lipoma
uterine tone and proper hemostasis. The newborn is either Laryngocele
taken to an adjoining operating room for further resuscita- Lymphatic malformation
tion and completion of the neck mass resection or to the Nuchal edema
Parotid tumor
neonatal intensive care unit for further resuscitation and
Choristoma
stabilization. Neural tube defects
Occipital encephalocele
Cervical myelomeningocele
Twin sac of a blighted ovum
EXIT procedure for airway compromise Causes of intrinsic obstruction
Laryngeal atresia
Laryngeal stenosis
Reversal of tracheal occlusion Laryngeal web
Tracheal atresia
Tracheal stenosis
The EXIT procedure was developed to manage cases of Laryngeal cyst
congenital diaphragmatic hernia in which tracheal clipping
Adapted from Crombleholme TM, Albanese CT. The fetus with airway
was accomplished antenatally. These cases required a sys-
obstruction. In: Harrison, Evans, Adzick, Holzgreze, eds.: The Unborn
tematic approach in which tracheal occlusion was reversed Patient, The Art and Science of Fetal Therapy, chap 24. Philadelphia,
before the baby was delivered. The EXIT procedure allowed PA: WB Saunders, 2001: 357–71.
time for neck dissection while the fetus was still on placen-
112 Seminars in Pediatric Surgery, Vol 15, No 2, May 2006

mass effect or to intrinsic obstruction of the larynx or

trachea. A number of fetal neck masses have been reported
to cause fetal airway obstruction (Table 2). The vast major-
ity of cases of fetal airway obstruction are due to cervical
teratomas or lymphatic malformations. Other less common
conditions include fetal goiter and hemangioma. Cervical
lymphatic malformations present either as isolated lym-
phatic malformations that are diagnosed at birth in other-
wise healthy infants or those detected prenatally in the
second trimester. Lymphatic malformations 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, those 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 before 30
weeks’ gestation is high because of the significant incidence
of nonimmune hydrops. The natural history of prenatally
diagnosed cystic hygroma appears to be dependent on ges-
tational age at diagnosis, location of cystic hygroma and
most importantly, the presence or absence of associated Figure 4 MRI picture in sagittal view demonstrating a large
chromosomal or structural abnormalities.15 cervical teratoma. There is a 12 ⫻ 6-cm heterogeneous mass
compressing and displacing the fetal trachea.
Cervical teratomas are rare, with approximately 150 con-
genital cases described.16 Teratomas are composed of tis-
sues foreign to their anatomic site, with all three germ layers location, and gestational age at presentation. In addition,
represented. Neural tissue is the most common histologic it is difficult to evaluate the airway and surrounding
component, with cartilage and respiratory epithelium also tissues of the neck solely by US.
observed. Cervical teratomas are thought to originate from Hubbard and coworkers described the first cases of giant
either totipotential germ cells or result from abnormal de-
neck masses evaluated by fetal magnetic resonance imaging
velopment of a conjoined twin. These lesions are usually
(MRI). These authors concluded that the half-Fournier sin-
large and bulky, typically ranging from 5 to 12 cm in
gle-shot turbo spin-echo (HASTE) images provide the best
diameter. Tumors greater than the size of the fetal head have
anatomic definition of the fetus and neck mass (Figure 4). In
also been reported. They can extend from the mastoid pro-
this study, fetal MRI provided a correct diagnosis of the
cess and body of the mandible, superiorly displacing the ear,
tumor in each case. It also provided better detail about the
to the clavicle and sternal notch. Posteriorly, they can reach
size and position of the mass and its anatomic relationship
the anterior border of the trapezius. Cervical teratomas can
to the airway compared with US.18
extend into the floor of the mouth or involve the tongue
(epignathus) or extend into the mediastinum. They may be The improved visualization of the relationship of the
associated with other congenital anomalies, such as chon- mass to the entire airway may help predict which patients
drodystrophia fetalis, imperforate anus, hypoplastic left are at the highest risk for airway obstruction, and thus the
ventricle, trisomy 13, and mandibular hypoplasia.17 need for the EXIT strategy. There has been some concern
Polyhydramnios is present in up to 40% of prenatally about performing MRI on the developing fetus. Neverthe-
diagnosed cases and is more commonly observed in asso- less, follow-up studies of prenatal MRI have not demon-
ciation with large tumors. In these cases, polyhydramnios is strated any deleterious effects in humans.19 The current
caused by the obstruction of the fetal esophagus. recommendation in the diagnosis of fetal neck masses is
The prenatal diagnosis of giant fetal neck masses was thus ultra-fast fetal MRI.
conventionally based on the use of maternal–fetal US. As fetuses with prenatally diagnosed fetal airway ob-
Cystic hygromas typically appear as multiloculated cystic struction reach viability, they should be monitored closely
masses with poorly defined borders that infiltrate the for the development or progression of hydrops or cardiac
normal structures of the neck. This contrasts with the decompensation. If the development or progression of hy-
usually well-defined borders of cervical teratomas. The drops is noted sonographically, open fetal surgery may be
differentiation of a cervical teratoma from a lymphatic necessary to salvage patients younger than 30 weeks’ ges-
malformation is sometimes difficult due to the similari- tation. If hydrops is noted later than 30 weeks’ gestation, the
ties in size, sonographic findings, clinical characteristics, fetus should be delivered by using the EXIT strategy.
Marwan and Crombleholme EXIT Procedure
Table 3 Pitfalls of the EXIT procedure
Failure to achieve adequate uterine relaxation
Failure to treat polyhydramnios
Failure to plan for fetal position relative to hysterotomy
Failure to use uterine staples
Failure to use deep inhalational anesthesia
Failure to maintain adequate maternal blood pressure
Failure to recognize cord compression
Failure to recognize placental abruption
Failure to make airway first fetal priority
Failure to be prepared for every airway challenge
Failure to allow sufficient time for return of uterine tone
Failure to use armored endotracheal tube (ETT)
Failure to confirm ETT tip position bronchoscopically
Failure to maintain uterine volume
Failure to perform adequate intrapartum fetal monitoring
Failure to recognize maternal indications for terminating EXIT
Failure to recognize fetal indications for terminating EXIT
A number of important considerations must be taken into
account when applying the EXIT procedure in the setting of
giant fetal neck masses. 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. Air-
way 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 previously, the surgeon
must be prepared for every possible airway contingency. All
the available modalities to secure the fetal airway are de-
tailed 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 associ-
ated 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 under-
estimation of the proximity of the placental edge to the site
of hysterotomy with increased risk of bleeding); and (4)
some fetal neck masses are caused by a cystic mass lesion. In
such cases, decompression of the mass before the hysterotomy
113
Compromise uteroplacental gas exchange
Inaccurate mapping of placental edge-Hemorrhage
Difficult exposure for delivery of head
Maternal hemorrhage
Inadequate uterine relaxation-Poor uteroplacental gas exchange
Poor uterine artery perfusion or compromised uteroplacental gas
exchange
Fetal bradycardia
Fetal hemorrhage
May have to end EXIT acutely due to abruption, or persistent fetal
bradycardia
Fetal death. Must not assume that laryngoscopy will be successful.
Must be prepared for bronchoscopy, tracheostomy, and/or mass
resection
Uterine atony and maternal hemorrhage
Collapse of fetal endotracheal tube by tumor compression
Malpositioned ETT. This is especially important with cervical or
mediastinal tumors
Acute loss of uterine volume may predispose to placental
abruption.
Unrecognized fetal distress or bradycardia
Maternal hemorrhage
Fetal bradycardia or arrest, fetal hemorrhage, or hypoxic brain
injury
under US guidance will help in fashioning the hysterotomy and
in delivering the fetal head and neck. Based on our cumulative
experience in the application of the EXIT procedure in differ-
ent clinical situations, we have summarized pitfalls and lessons
learned to provide guidance when applying the EXIT approach
(Table 3).
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 the cases die in utero or are still-
born. There are multiple etiologies for the intrinsic obstruc-
tion of the airway in CHAOS including: laryngeal atresia,
laryngeal web, tracheal atresia, and laryngeal cyst. Despite
these multiple etiologies, the clinical features and presenta-
tion of these cases is the same, consisting of: bilaterally
enlarged echogenic lungs, dilated airways, and flattened or
inverted diaphragms with associated fetal ascites and non-
immune hydrops (Figure 5). Previous studies using a fetal
lamb tracheal ligation model showed that the same effects
of CHAOS could be replicated. The investigators showed
that reversal of tracheal occlusion can reverse the conse-
114
Figure 5 MRI picture in sagittal view demonstrating CHAOS in
a fetus at 26 weeks’ gestation. There is homogenous enlargement
of both lungs with inversion of the diaphragm and massive ascites.
quences of airway obstruction, including capillary leak syn-
drome, respiratory distress syndrome, tracheobronchomala-
cia, and diaphragmatic dysfunction.21 Lim and coworkers22
reported a series in which the prenatal natural history of
CHAOS may be less dismal than previously thought. It is
clear that, in some cases, hydrops may completely resolve in
the third trimester as a result of tracheolaryngeal 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, such as
absent radius, anophthalmia, cardiac anomalies, esophageal
atresia, Fraser syndrome, and genitourinary anomalies. A
fetus with laryngeal atresia and associated malformations of
the esophagus and trachea does not develop the typical
manifestations of CHAOS (eg, hydrops) because the tra-
cheobronchial tree can decompress. As the natural history of
CHAOS is not completely understood, once a fetus has been
diagnosed with this condition, ongoing close surveillance
for the remaining period of gestation is required. In severe
cases, 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.23 It allows the adequate control of the
fetal airway by surgical tracheostomy. Once delivered, these
infants require prolonged ventilation and even longer sur-
Seminars in Pediatric Surgery, Vol 15, No 2, May 2006
gical 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-extracorporeal membrane oxygenation
(ECMO) strategy
The EXIT procedure is also useful in fetuses with severe
pulmonary or cardiac malformations in which separation
from the uteroplacental circulation leads to immediate in-
stability in the new born. In such cases, an EXIT-to-ECMO
strategy allows the securing of the airway and the insertion
of venous and arterial cannulas for ECMO while on placen-
tal support. This approach avoids any period of hypoxia or
acidosis during neonatal resuscitation. We currently are
offering EXIT-to-ECMO in fetuses with high-risk CDH.
These fetuses have lung– head circumference ratios less
than 1.0 and have associated liver herniation, placing them
in the highest risk category for mortality and morbidity. We
also offer EXIT-to ECMO for fetuses with severe aortic
stenosis or hypoplastic left heart syndrome (HLHS) when
associated with a restrictive atrial septum. In these cases,
severe instability in the delivery room is anticipated. As
such, infants can be stabilized and then taken to the cathe-
terization laboratory.
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 malformations or mediastinal teratomas
that compromise 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.24 Resec-
tion facilitates postnatal ventilation and improves venous
return to the heart, which is essential for the successful
ECMO when severe pulmonary hypoplasia exists.
EXIT-to-separation strategy in conjoined twins
In 2002, Bouchard and coworkers9 reported the use of the
EXIT procedure as a bridge to separation of a set of thora-
coomphalopagus conjoined twins, one of whom had a ru-
dimentary 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.
Marwan and Crombleholme EXIT Procedure
Complications of the EXIT procedure
The EXIT procedure is associated with an increased poten-
tial risk of maternal bleeding due to uterine hypotonia in-
duced by high concentrations of inhalational agents. These
high levels 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, in our
experience, the mean blood loss with EXIT procedures has
been equivalent to that observed in cesarian sections. Early
in our experience, we had to transfuse a patient in whom
polyhydramnios caused us to underestimate the proximity
of the placenta to the hysterotomy. In a review of the
experience of clinicians at the University of California at
San Francisco, a slightly higher incidence of wound infec-
tion was reported with EXIT procedures than with cesarean
sections. Although the EXIT procedure is specifically de-
signed to optimize outcomes for the fetus, if it is not per-
formed appropriately, there is also the potential for fetal
complications. These are primarily related to failure to pre-
serve 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. Al-
though it was originally described for the reversal of tra-
cheal occlusion in fetuses with severe CDH, the period of
uteroplacental bypass that it affords can be used in various
other settings in which cardiopulmonary compromise is
anticipated. The EXIT procedure provides the surgeon with
the luxury of transforming a potentially fatal neonatal emer-
gency to a controlled clinical environment that is more
likely to result in a better outcome.
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