Fetal Surgery for Congenital High Airway Obstruction

Congenital high airway obstruction syndrome (CHAOS) is defined by complete or near-complete obstruction of the upper airway and appears radiographically as echogenic large lungs, flattening or inversion of the diaphragm, and dilation of the tracheobronchial tree.[1, 2] It is a rare antenatal diagnosis whose true incidence is unknown, though it is likely more common than has been reported, in that many fetuses with the syndrome die in utero or are stillborn.[3, 4, 5, 6]

As the name suggests, CHAOS results from obstruction of the upper airway. Causes include laryngeal atresia, subglottic stenosis, and laryngeal or tracheal rings or agenesis. Laryngeal and tracheal anomalies may be associated with Fraser syndrome, a congenital disorder characterized by ambiguous genitalia, urinary tract anomalies, cryptophthalmos, and syndactyly.[7]  The literature is scant, but a 2016 study by Tessier et al suggested that approximately 40% of neonates diagnosed with Fraser syndrome had evidence of CHAOS before birth.[8]

The pathophysiology of CHAOS results from trapping of pulmonary secretions, which are normally evacuated through the fetal upper airway. Secretions accumulate in the bronchopulmonary tree and cause hyperinflation of the lungs. Excessive distention of the lungs, in turn, leads to an increase in the intrathoracic pressure, compromising venous return and cardiac output and potentially resulting in nonimmune fetal hydrops. It is noteworthy that hydrops is better tolerated by patients with CHAOS than by those with other congenital abnormalities associated with hydrops.

CHAOS is often diagnosed in the second trimester by means of ultrasonography (US), but it has been diagnosed as early as the first trimester. It is suggested by large echogenic lungs, flattening or bowing of the diaphragm, and fetal hydrops.[9]  Historically, fetal demise was unavoidable in the presence of CHAOS, but with the advent of the ex-utero intrapartum treatment (EXIT) procedure, survival rates have drastically improved.[10, 11, 12, 13]

The natural history of CHAOS is grim, with only one patient in 48 surviving the disease in the pre-EXIT era.[1] ​ Accordingly, the authors currently recommend that all viable fetuses with CHAOS undergo EXIT delivery. Rare instances of survival without an EXIT delivery have been described among patients with a concurrent tracheoesophageal fistula (TEF), providing a passage for evacuation of pulmonary secretions.[14]

In select patients who present with life-threatening hydrops and short-segment lesions or webs, fetoscopy with wire tracheoplasty may be of some benefit.[15]  Determining which patients are more likely to benefit from tracheoplasty poses a great challenge, and this procedure is typically reserved for fetuses who present with hydrops early in pregnancy (17-30 weeks’ gestation).

Because patients with CHAOS seem to tolerate hydrops better than those with other disease processes, expectant management is generally preferred for those who present later in the third trimester until an EXIT delivery can safely be performed. 

Given the complexity of in-utero management of CHAOS and the challenges of managing the difficult airway at birth, it is recommended that these cases be referred to a fetal care center.[16, 17]

Contraindications may be either maternal or fetal in origin. Maternal contraindications include the following:

• Frequent contractions
• Membrane rupture
• Short cervix
• Uncontrolled comorbidities that may predispose the patient to preeclampsia or HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome

Fetal contraindications include the following:

• Multiple fetal anomalies
• Chromosomal abnormalities
• Anatomic restrictions, including an anterior-lying placenta, which may prohibit safe access

Best practices

An EXIT-to-delivery procedure is the procedure most frequently performed in fetuses with CHAOS. The authors' current practice is to offer an EXIT delivery of all viable fetuses and to offer fetoscopy with wire tracheoplasty to hydropic patients with CHAOS who present between 17 and 30 weeks' gestation. Outcome data are limited.  

Fetal wire tracheoplasty is considered early in pregnancy. It is a challenging procedure that requires considerable preoperative planning. The procedure is performed fetoscopically under US guidance to avoid injury to the placenta. The fetal lie is a critical consideration because a direct path is required to introduce the fetal bronchoscope and guide wire; the procedure can be challenging, if not prohibitive, if the fetal head orientation is unfavorable. (See the image below.)

Fetoscopic approach for in utero tracheoplasty

In-utero laser treatment has also been described. In select cases, fetal US has been used to diagnose laryngeal atresia or tracheal web as the underlying cause of CHAOS. In one case, fetoscopic membrane perforation was performed successfully, resulting in lung size normalization and resolution of hydrops.[18]

Procedural planning

The EXIT procedure requires careful planning with a multidisciplinary team, typically including two pediatric/fetal surgeons, one obstetrician, one neonatologist, one ultrasonographer, and one nurse scrub.

Complication prevention

Appropriate anesthesia and tocolytics are important to prevent uterine contractions and placental separation. Uterine atony can lead to diffuse bleeding, and a special uterine stapler (uterine stapler with absorbable staples [US Surgical Corporation, Norwalk, CT]) can reduce the risk of hemorrhage during the EXIT procedure.

Because CHAOS is a very rare disease and viability beyond the immediate neonatal period became a reality only with the implementation of the EXIT procedure in 1998 and 2000, outcome data are limited.[10, 11, 12]  Case series support the assertion that long-term and tracheostomy-free survival are possible.[15]

Outcomes may depend on other anomalies, given that fetuses with CHAOS frequently have additional congenital abnormalities diagnosed postnatally. In one series, three of four fetuses with hydrops who underwent fetal intervention had other congenital abnormalities, consisting of prune-belly syndrome, imperforate anus, and fragile X syndrome.[15] In cases of isolated CHAOS without hydrops, outcomes are more favorable and frequently require shorter periods of postnatal ventilator support.[19]

Despite remarkable progress in CHAOS management, tracheostomy dependence and speech impediments are to be expected.

A diagnosis of CHAOS in the midsecond trimester suggests a poor prognosis, in that many progress to in-utero fetal demise (IUFD). Patients who present in the third trimester without signs of hydrops frequently survive until delivery, as they typically have only a partial obstruction.

Before being offered fetal wire tracheoplasty or an ex-utero intrapartum treatment (EXIT) delivery for congenital high airway obstruction syndrome (CHAOS), patients should be counseled regarding the particular upper airway malformation and possible outcomes. Discussing the possibility of permanent tracheostomy and lifelong speech impairment is essential. From a maternal standpoint, depending on placental location, a classic hysterotomy may be required, prohibiting the possibility of future vaginal deliveries.

Anesthesia

Inhaled anesthetics, particularly isoflurane[20, 21] , are necessary for uterine relaxation and uteroplacental gas exchange, which has been demonstrated to be normal up to 54 minutes on uteroplacental support during EXIT delivery.[22]

Alpha-adrenergic agonists are frequently required to maintain the maternal blood pressure; high levels of isoflurane, needed for uterine relaxation, can cause hypotension. Additionally, nitroglycerin may help with uterine relaxation; activation of guanylyl cyclase leads to increased levels of cyclic guanosine monophosphate (cGMP) and decreased levels of intracellular calcium, thereby causing the uterus to relax. Typically, a fetal cocktail consisting of a paralytic and narcotic agent is administered directly into the fetus via an intramuscular injection.

Positioning

The patient is typically placed in the supine position on the operating room table. Occasionally, the patient may be placed in lithotomy position to increase available space for operating room staff.

Because fetal intervention increases the risk of preterm premature rupture of the membrane and preterm delivery, patients must be monitored closely following a fetal wire tracheoplasty, and any changes in fetal movement or maternal complications should prompt immediate evaluation.

During EXIT deliveries, given the propensity for bleeding, the maternal hematocrit is measured preoperatively and postoperatively; prior to incision, 4 units of typed and crossed blood is prepared.

After birth, follow-up computed tomography (CT) or magnetic resonance imaging (MRI) is commonly performed to confirm the diagnosis, to delineate anatomy, and to screen for tracheoesophageal fistula (TEF). Surgical management can be elective once an airway is established and a TEF is ruled out.

Bronchoscopy should be performed during the neonatal period; laryngeal obstructions frequently result from laryngeal cysts or webs and can occasionally be resected or ablated endoscopically.

During the procedure, fetal pulse oximetry is used to continuously monitor fetal oxygenation. With uteroplacental support in place (see the first image below), endotracheal intubation is attempted (see the second image below).

EXIT procedure with fetus maintained on uteroplacental circulation

Intubation during EXIT procedure

If unsuccessful, the next step is rigid bronchoscopy with or without wire tracheoplasty. If this attempt fails, a tracheostomy is performed (see image below).

Tracheostomy performed during EXIT procedure for difficulty obtaining an oral airway

Ex-utero intrapartum treatment (EXIT) deliveries can lead to tremendous blood loss. Tocolytics and inhaled anesthetics are used to reduce contractions and frequently result in uterine atony. To minimize blood loss during the hysterotomy, a specific uterine stapler device with absorbable staples is required.

It is paramount to preserve placental blood flow, which requires profound uterine relaxation and caution in entering the uterus. Anterior placentas frequently necessitate a posterior uterine incision in an attempt to avoid placental injury and chorioamniotic separation, which can disrupt uteroplacental gas exchange. Additionally, care should be taken to minimize manipulation of the umbilical, which may result in vessel spasm and compromised blood flow.

If necessary, the procedure can last several hours.