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Immediate operative management of the fetus with airway anomalies resulting from congenital malformations
Seminars in Fetal & Neonatal Medicine xxx (2016) 1e6
Contents lists available at ScienceDirect
Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny
Review
Immediate operative management of the fetus with airway anomalies resulting from congenital malformations Pablo Laje a, *, Sasha J. Tharakan b, Holly L. Hedrick a a b
The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA Department of Pediatric Surgery, University Children's Hospital Zurich, Zurich, Switzerland
s u m m a r y Keywords: Ex-utero intrapartum treatment CHAOS syndrome Congenital airway obstruction Cervical teratoma Cervical lymphangioma Congenital cystic adenomatoid malformation (CCAM)
Prenatal diagnosis has transformed the outcome of fetuses with airway obstruction. The thorough evaluation of prenatal imaging allows for categorizing fetuses with airway compromise into those who will require a special mode of delivery and those who can be delivered without any special resources. The ex-utero intrapartum treatment (EXIT) approach allows accessing the airway while the fetus is under placental support, converting a potentially catastrophic situation into a controlled one. An expert multidisciplinary team is the key to success. © 2016 Elsevier Ltd. All rights reserved.
1. Introduction Fetuses with airway obstruction at delivery are at great risk of hypoxic brain injury and mortality. The advent of prenatal diagnostic strategies galvanized the perinatal management of such fetuses. The first example of this was reported by Holinger et al. in 1985. Prenatal diagnosis of a cervical teratoma allowed for special airway equipment to be pre-emptively mobilized to the delivery room prior to cesarean delivery. Direct laryngoscopy and bronchoscopy was used to secure the airway immediately after delivery [1]. The concept of accessing an obstructed airway while keeping the fetus under placental support was first reported by Kelly et al. in 1990, in which direct laryngoscopy was performed to secure the airway [2]. A few months later, Levine et al. reported the sentinel case of a tracheostomy performed on a fetus under placental support in order to secure an airway [3]. No maternal interventions to prevent uterine contractions were performed in these reports, and the fetuses were entirely delivered from the uterus prior to airway manipulation. During the early 1990s this concept evolved until, in 1996, a team at University of California, San Francisco, described a standardized procedure called ex-utero intrapartum treatment (EXIT) [4]. They reported the reversal of a tracheal occlusion in patients with prenatally treated congenital diaphragmatic hernia.
The EXIT procedure is now the gold standard strategy for delivering fetuses with congenital airway obstruction. It permits the fetal airway to be secured in an elective, controlled manner while the fetus remains under placental support. Once adequate ventilation is secured, the fetus can be safely taken off placental support. The indications for an EXIT procedure have grown over time and now include a myriad of conditions, including cervical lymphangiomas, cervical teratomas, large congenital lung malformations, conjoined twins, and congenital high airway obstruction syndrome (CHAOS) [5e7]. Successful performance of an EXIT procedure rests on both thorough preoperative planning and the availability of a highly skilled multidisciplinary team. 2. Prenatal assessment It is of paramount importance to establish an early diagnosis in order to facilitate a prompt referral of the mother and fetus to a center proficient in performing an EXIT and fetal surgery. The prenatal evaluation of a fetus with airway obstruction includes amniocentesis and other genetic tests, if warranted, but, most importantly, a thorough assessment of the fetal anatomy with fetal three-dimensional ultrasound, fetal echocardiography and ultrafast fetal magnetic resonance imaging (Figs 1 and 2). 3. Team approach and equipment
* Corresponding author. Address: The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA. Tel.: þ1 215 510 8244. E-mail address: [email protected] (P. Laje).
The EXIT procedure can only be successful if performed by a multidisciplinary team that includes anesthesiologists, pediatric surgeons, neonatologists, maternalefetal medicine specialists,
http://dx.doi.org/10.1016/j.siny.2016.04.003 1744-165X/© 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Laje P, et al., Immediate operative management of the fetus with airway anomalies resulting from congenital malformations, Seminars in Fetal & Neonatal Medicine (2016), http://dx.doi.org/10.1016/j.siny.2016.04.003
2
P. Laje et al. / Seminars in Fetal & Neonatal Medicine xxx (2016) 1e6
fetal cardiologists, and a committed group of operating room nurses and personnel. Extensive preoperative planning, simulations, and ad-hoc team meetings are mandatory. The entire range of airway equipment needs to be sterilely available, including rigid infant-type laryngoscope handles, a set of number 0, 1 and 2 straight Miller blades, rigid ventilating bronchoscopes (sizes 2.5 and 3.0), wire-reinforced cuffless endotracheal tubes (ETTs), tracheostomy tubes, and all surgical instruments required for a neonatal tracheostomy. Once the airway is established, a sterile Mapleson circuit with a manometer and a 1 L bag is used on the sterile surgical field to help ventilate the fetus. Fetuses undergoing an EXIT procedure frequently need immediate post-EXIT surgical interventions for which, ideally, a second operating room must be readily available next to the room where the EXIT takes place. 4. Timing of delivery
Fig. 1. Cervical teratoma as seen on three-dimensional ultrasound imaging. Reprinted with permission from Lioy J, Sobol S editors. Disorders of the neonatal airway: fundamentals for practice, p. 182. © Springer, 2015.
Under ideal circumstances, a fetus with airway obstruction should reach term and be electively delivered. However, this may not be possible in some situations as the cause of airway obstruction and its effects on fetal health may dictate otherwise. For example, large cervical tumors may result in compression of the airway and the pharynx/esophagus, resulting in polyhydramnios and medically unresponsive preterm labor. When a mother carrying a fetus with airway obstruction develops signs of impending labor (such as severe recurrent polyhydramnios or shortened uterine cervix) it is crucial to perform an elective preterm EXIT at a time of day when required personnel are available. This is preferable to waiting for the fetus to reach term due to the risk of developing labor at off-hours when the resources necessary for an EXIT may not be easily available. A large published series of fetuses with cervical teratomas having undergone an EXIT reported that only 23% of the fetuses reached term [8]. 5. Ex-utero intrapartum treatment
Fig. 2. Ultra-fast prenatal magnetic resonance imaging. (A) Twin pregnancy with one fetus with a cervical teratoma (black arrow). (B) Giant cervical teratoma (white arrow) in a fetus with cystic and solid components. Reprinted with permission from Lioy J, Sobol S editors. Disorders of the neonatal airway: fundamentals for practice, p. 182. © Springer, 2015.
Undoubtedly, deep maternal general anesthesia is essential for a successful EXIT procedure, as general anesthetic drugs are the strongest uterine relaxants currently known and utero-placental gas exchange only happens if the uterus is relaxed. In order to facilitate the management of postoperative maternal pain, an epidural catheter is employed. The mother is meticulously monitored during the EXIT procedure with continuous electrocardiogram, pulse oximetry, invasive monitoring of arterial blood pressure, urinary output with a catheter, core body temperature and peripheral nerve stimulation. The combination of drugs used for induction and maintenance of anesthesia during an EXIT procedure may vary, but the principle of deep inhalational anesthesia must not change. The cornerstone from an anesthesiologist’s point of view is to maintain the fetaleplacental circulation, which requires adequate uterine relaxation and maintenance of uterine perfusion pressure. Two patients must be anesthetized for the benefit of one, and there is little margin for error [9]. The induction of maternal anesthesia is usually done with intravenous propofol (2 mg/kg) closely followed by a muscle relaxant such as succinylcholine (1 mg/kg) to facilitate a rapid endotracheal intubation. Maintenance of anesthesia is done with desflurane (5e10%) titrated to uterine tone as evaluated by direct palpation during the procedure. Vecuronium (0.1 mg/kg/dose boluses, repeated pro re nata) is used for muscle relaxation. Maternal hypotension may occur as a response to the deep general anesthesia required to facilitate uterine relaxation. This must be
Please cite this article in press as: Laje P, et al., Immediate operative management of the fetus with airway anomalies resulting from congenital malformations, Seminars in Fetal & Neonatal Medicine (2016), http://dx.doi.org/10.1016/j.siny.2016.04.003
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aggressively treated with an alpha-1-adrenergic agonist (phenylephrine) as a continuous infusion (10e200 mg/min) closely titrated during the procedure to maintain the maternal mean arterial pressure >60 mmHg. A continuous dopamine infusion may also be used. With the completion of the procedure and the clamping of the umbilical cord, uterine contraction is induced with intravenous oxytocin (50 U) administered to the mother. Methylergonovine, carboprost, and misoprostol may also be used if needed. The EXIT procedure involves a higher risk of complications for the mother than a standard cesarean section. Specifically, the risks of general anesthesia are higher than epidural anesthesia. Even more significantly, during the EXIT procedure the purposeful inhibition of uterine contractions with deep anesthesia is a set-up for uterine hemorrhage following detachment of the placenta. Whereas the average blood loss for a standard cesarean section may be 500e600 mL, EXIT procedures have been reported to have an average blood loss of >1000 mL [10,11]. The unique characteristics of anesthesia required for prolonged placental support of the fetus mandate that an anesthesiologist familiar with these procedures be involved.
tumor, the next step is rigid bronchoscopy. This technique can decompress and straighten the airway, to a certain degree, as it is advanced distally. Gentle external manipulation of a large cervical mass may help relieve some compression and deviation of the airway, aiding in bronchoscopic visualization of the airway. Rigid bronchoscopy can also be used to maneuver a wire into the distal airway that can be used as a guide for advancing an endotracheal tube (Seldinger-like technique). Rigid bronchoscopy can help to delineate the relationship of the larynx and trachea relative to a tumor should a surgical airway be required (Fig. 3). If the cervical tumor contains large cysts, decompression utilizing an ultrasound-guided percutaneous drainage during the EXIT can increase airway visualization and the chances of a successful orotracheal intubation. Pedunculated tumors obstructing the airway, such as oropharyngeal tumors (epignathus, epulis), may be resected during the EXIT procedure (Fig. 4). The EXIT procedure provides time for surgical resection and establishing a secure airway thereafter [12].
6. Exposure of the fetus during the EXIT
If laryngoscopy and bronchoscopy is unsuccessful in establishing a secure airway, such as in the case of severe macroglossia (Fig. 5), the placement of a tracheostomy is necessary. Performing a tracheostomy in this setting can be an extremely challenging procedure due to the presence of large cervical tumors (particularly cervical teratomas). Therefore, preoperative evaluation of fetal radiologic imaging, prior to the EXIT, is vital to visualize the relationship between the tumor and the airway. This essential step can save valuable intraoperative time should a surgical airway be needed [13]. Preoperative examination of fetal imaging can help predict (to a certain degree) the likelihood of a successful orotracheal intubation. Whereas solid tumors, such as teratomas, may be more aggressive, cystic tumors such as lymphatic malformations may be pliable and are usually not destructive or invasive. Cervical teratomas, as they grow, pull the trachea and lungs superiorly against the thoracic inlet. This phenomenon may result in various degrees of pulmonary hypoplasia. In contrast, pulmonary hypoplasia is not seen in patients with cervical lymphangioma [14]. In
Only the area of the fetus that is going to be operated on should be exteriorized through the hysterotomy, while the rest of the fetus must stay within the uterine cavity to maintain uterine volume and fetal temperature. This concept pertains to all EXIT and fetal surgery procedures. In cases of airway obstruction, the head, neck, upper extremities, and upper torso are exteriorized. A pulse oximeter (enclosed with aluminum foil and a Tegaderm (3M, St Paul, MN, USA)) and a 24-gauge intravenous catheter are placed using the upper extremities. Fetal vital signs are watched intraoperatively with a pulse oximeter and continuous sterile intraoperative echocardiography performed by a cardiologist who is scrubbed in with the operating team. Fetal anesthesia is achieved through the placenta, but must be supplemented with a single intramuscular dose of an opioid (fentanyl, 0.2 mg/kg), and a muscle relaxant (vecuronium, 0.1 mg/ kg) once the fetus has been exposed. Such medications (and all other drugs such as atropine, epinephrine, and calcium that are potentially needed at the time of a code) are preoperatively drawn up in sterile syringes and made ready for use on the operating table. Drugs, crystalloid solutions and blood may be given to the fetus as required through the intravenous line. Frequently the fetus requires a variety of interventions during the EXIT procedure due to alterations in vital signs. Fetal bradycardia and myocardial dysfunction are not rare. These conditions, particularly when they are acute, prompt immediate investigation. Cord compression may be the culprit and can be quickly relieved by fetal repositioning and increased amnio-infusion. Fetal cardiac dysfunction due to hypovolemia must be quickly recognized and treated with a fetal transfusion of packed red blood cells.
8. When is a tracheostomy necessary?
7. Management of the fetal airway The first intervention should always be performance of direct laryngoscopy to identify the vocal cords and fetal airway. This can be best achieved after the fetal head is exteriorized and after a shoulder roll is placed, allowing for neck extension. If the vocal cords are visible without significant obstruction from a tumor, an attempt is made to intubate the trachea employing the laryngoscope. However, if the airway is not clearly delineated with direct laryngoscopy due to deviation, compression, or invasion by a
Fig. 3. Bronchoscopy performed during an ex-utero intrapartum therapy (EXIT) procedure in a fetus with a giant cervical mass (black triangle) may help delineate critical airway anatomy. Reprinted with permission from Lioy J, Sobol S editors. Disorders of the neonatal airway: fundamentals for practice, p. 185. © Springer, 2015.
Please cite this article in press as: Laje P, et al., Immediate operative management of the fetus with airway anomalies resulting from congenital malformations, Seminars in Fetal & Neonatal Medicine (2016), http://dx.doi.org/10.1016/j.siny.2016.04.003
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Fig. 5. Severe macroglossia necessitating potential tracheostomy during ex-utero intrapartum therapy (EXIT) procedure.
the tumor has been removed (because the area is left with large floppy skin flaps), may be a difficult situation. Two different techniques may be employed to address this challenge. First, by tunneling a regular ETT under the skin through a skin incision lateral to the midline before entering the trachea, the ETT may be used in place of a tracheostomy tube. Second, after the trachea is dissected from the tumor, a 4e8F nasogastric (NG) tube may be threaded retrograde within the airway through a tracheostomy incision in the trachea and pulled up through the oral cavity. Next, the ETT is sutured to the NG tube tip and then the NG tube is pulled back through the neck in order to guide the ETT antegrade into the optimal position in the trachea. This technique is called retrograde intubation (Fig. 6).
Fig. 4. Oropharyngeal tumors present at birth may be life-threatening. (A) Fetus with multiple epulis originating from the upper and lower alveolar ridges. (B) Giant epignathus necessitating ex-utero intrapartum therapy (EXIT) procedure and placement of a tracheostomy. Courtesy of Alan Flake, MD; reprinted with permission from Lioy J, Sobol S editors. Disorders of the neonatal airway: fundamentals for practice, p. 186. © Springer, 2015.
our extensive experience, 53% of fetuses with cervical teratomas required a tracheostomy at the time of the EXIT, compared with only 8% of fetuses with cervical lymphangiomas [8]. To perform a tracheostomy, a transverse incision is usually made one to two fingerbreadths above the sternal notch, and extended to the side of the neck to which the airway is deviated. Once the airway is identified, tumor is dissected from the airway to relieve the compression and perform the tracheostomy at the appropriate level. The anatomy may not be as readily apparent since the carina may be located as high as the level of the sternal notch, an effect from the upward deviation of the trachea by the tumor. Ideally, the tracheostomy should be performed at the level of the second or third tracheal ring, but this is often a difficult task due to severe alteration of the anatomy. Once a tracheostomy is safely performed, securing the tracheostomy tube to any cervical structures, either while the tumor is still present (because of the mass effect) or after
Fig. 6. Retrograde intubation. A nasogastric tube (white arrow) is passed retrograde from the tracheostomy to the mouth and is used to guide the endotracheal tube (asterisk) antegrade into the airway.
Please cite this article in press as: Laje P, et al., Immediate operative management of the fetus with airway anomalies resulting from congenital malformations, Seminars in Fetal & Neonatal Medicine (2016), http://dx.doi.org/10.1016/j.siny.2016.04.003
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Manual ventilation is initiated on the operative field immediately after the airway is established and secured. If the fetus is <34 weeks of gestation, surfactant is administered. Additionally, if the fetus is stable, prior to clamping and dividing the umbilical cord, umbilical arterial and venous lines can be placed. When performing the EXIT procedure for a fetus with CHAOS syndrome, the diagnosis is confirmed and the proximal airway is evaluated with direct laryngoscopy and bronchoscopy. Ultimately, however, a tracheostomy is always mandatory. After securing an airway, the fetal portion of the EXIT procedure concludes and the newborn is taken to an adjoining resuscitation room. In caring for the mother, the placenta is delivered, uterine tone is quickly restored, and both the uterine and abdominal walls are closed in a similar fashion as performed in a cesarean section. If a congenital airway obstruction is present in a twin pregnancy, the healthy twin should be delivered first if possible [15]. Due to the presence of anesthetic gases from maternal exposure, immediate endotracheal intubation and respiratory support of the healthy twin is essential. 9. EXIT procedure for other airway malformations When a fetus with a giant lung mass, such as congenital cystic adenomatoid malformation (CCAM) or bronchial atresia, is anticipated to have profound respiratory insufficiency from severe mediastinal shift and compression of the healthy contralateral lung, the mode of delivery should also be an EXIT procedure. The prenatal natural history of fetal lung lesions ranges from lesions that spontaneously regress during the third trimester, to lesions that rapidly expand resulting in hydrops and in-utero demise. Large tumors may cause extreme mediastinal shift, leading to vena cava obstruction, cardiac compression, and ultimately fetal hydrops. The mass effect may also lead to relative pulmonary hypoplasia and compromised function of the remaining lung [16]. The CCAM volume ratio (CVR) has been used to track tumor growth and regression during gestation. Elevated CVR (>1.6) at presentation correlates with the development of hydrops, need for fetal intervention, need for ventilatory support, need for extracorporeal membrane oxygenation (ECMO), length of postnatal hospital stay, and survival [17]. In a series of nine patients, the EXIT procedure allowed for controlled resection of large fetal lung lesions at delivery, avoiding acute respiratory decompensation related to mediastinal shift, air trapping, and compression of normal lung. Overall survival after EXIT for lung mass resection was 89%. The average time on placental bypass was 65 min. Veno-arterial ECMO was used in four neonates for persistent pulmonary hypertension postnatally. During the EXIT procedure, the airway is safely secured via endotracheal intubation and the lung mass is resected with the fetus supported by placental circulation [18]. If the mediastinal shift is severe, but not extreme, the fetus can be delivered by the “cesarean section-to-resection” strategy, in which the fetus is intubated immediately after the cesarean section and the lung resection is done immediately after that. 10. Conclusions Delivering a fetus with airway obstruction without the required resources invariably results in death or permanent brain damage. The EXIT procedure, albeit complex, allows access to the fetal airway in a controlled and secure manner while the fetus is still under placental support. A skilled multidisciplinary team that performs fetal surgery on a regular basis is the key to success.
5
Practice points The EXIT procedure is the gold standard strategy for delivering a fetus with congenital airway obstruction as it permits the fetal airway to be secured in an elective, controlled manner while the fetus remains under placental support. The EXIT procedure can only be successful if performed by a multidisciplinary team that includes anesthesiologists, pediatric surgeons, neonatologists, maternal fetal medicine specialists, fetal cardiologists, and a group of operating room nurses and personnel. When a mother carrying a fetus with airway obstruction develops signs of impending labor it is crucial to perform an elective preterm EXIT at a time of day when required personnel are available. Tracheostomy is necessary if laryngoscopy and bronchoscopy during the EXIT procedure is unsuccessful in establishing an airway in a fetus with congenital airway obstruction.
Research directions The investigation and application of EXIT procedures for other fetal pathologies. Investigating how maternal and fetal morbidity may be further decreased in performing an EXIT procedure.
Conflict of interest statement None declared. Funding sources None. References [1] Holinger LD, Birnholz JC, Bruce DR, Rabin DN. Management of an infant with prenatal ultrasound diagnosis of upper airway obstruction. Int J Pediatr Otorhinolaryngol 1985;10:263e70. [2] Kelly MF, Berenholz L, Rizzo KA, Greco R, Wolfson P, Zwillenberg DA. Approach for oxygenation of the newborn with airway obstruction due to a cervical mass. Ann Otol Rhinol Laryngol 1990;99(3 Pt 1):179e82. [3] Levine AB, Alvarez M, Wedgwood J, Berkowitz RL, Holzman I. Contemporary management of a potentially lethal fetal anomaly: a successful perinatal approach to epignathus. Obstet Gynecol 1990;76:962e6. [4] Harrison MR, Adzick NS, Flake AW, VanderWall KJ, Bealer JF, Howell LJ, et al. Correction of congenital diaphragmatic hernia in utero VIII: response of the hypoplastic lung to tracheal occlusion. J Pediatr Surg 1996;31:1339e48. [5] Hedrick HL. Ex utero intrapartum therapy. Semin Pediatr Surg 2003;12: 190e5. [6] Liechty KW. Ex-utero intrapartum therapy. Semin Fetal Neonatal Med 2010;15:34e9. [7] Lim FY, Crombleholme TM, Hedrick HL, Flake AW, Johnson MP, Howell LJ, et al. Congenital high airway obstruction syndrome: natural history and management. J Pediatr Surg 2003;38:940e5. [8] Laje P, Johnson MP, Howell LJ, Bebbington MW, Hedrick HL, Flake AW, et al. Ex utero intrapartum treatment in the management of giant cervical teratomas. J Pediatr Surg 2012;47:1208e16. [9] Lin EE, Tran KM. Anesthesia for fetal surgery. Semin Pediatr Surg 2013;22: 50e5.
Please cite this article in press as: Laje P, et al., Immediate operative management of the fetus with airway anomalies resulting from congenital malformations, Seminars in Fetal & Neonatal Medicine (2016), http://dx.doi.org/10.1016/j.siny.2016.04.003
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[10] Butwick A, Aleshi P, Yamout I. Obstetric hemorrhage during an EXIT procedure for severe fetal airway obstruction. Can J Anaesth 2009;56:437e42. [11] Zamora IJ, Ethun CG, Evans LM, Olutoye OO, Ivey RT, Haeri S, et al. Maternal morbidity and reproductive outcomes related to fetal surgery. J Pediatr Surg 2013;48:951e5. [12] Laje P, Howell LJ, Johnson MP, Hedrick HL, Flake AW, Adzick NS. Perinatal management of congenital oropharyngeal tumors: the ex utero intrapartum treatment (EXIT) approach. J Pediatr Surg 2013;48:2005e10. [13] Hubbard AM, Crombleholme TM, Adzick NS. Prenatal MRI evaluation of giant neck masses in preparation for the fetal exit procedure. Am J Perinatol 1998;15:253e7. [14] Laje P, Peranteau WH, Hedrick HL, Flake AW, Johnson MP, Moldenhauer JS, et al. Ex utero intrapartum treatment (EXIT) in the management of cervical lymphatic malformation. J Pediatr Surg 2015;50:311e4.
[15] Liechty KW, Crombleholme TM, Weiner S, Bernick B, Flake AW, Adzick NS. The ex utero intrapartum treatment procedure for a large fetal neck mass in a twin gestation. Obstet Gynecol 1999;93:824e5. [16] Adzick NS, Flake AW, Crombleholme TM. Management of congenital lung lesions. Semin Pediatr Surg 2003;12:10e6. [17] Crombleholme TM, Coleman B, Hedrick H, Liechty K, Howell L, Flake AW, et al. Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung. J Pediatr Surg 2002;37:331e8. [18] Hedrick HL, Flake AW, Crombleholme TM, Howell LJ, Johnson MP, Wilson RD, et al. The ex utero intrapartum therapy procedure for high-risk fetal lung lesions. J Pediatr Surg 2005;40:1038e43. discussion 1044.
Please cite this article in press as: Laje P, et al., Immediate operative management of the fetus with airway anomalies resulting from congenital malformations, Seminars in Fetal & Neonatal Medicine (2016), http://dx.doi.org/10.1016/j.siny.2016.04.003
Contents lists available at ScienceDirect
Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny
Review
Immediate operative management of the fetus with airway anomalies resulting from congenital malformations Pablo Laje a, *, Sasha J. Tharakan b, Holly L. Hedrick a a b
The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA Department of Pediatric Surgery, University Children's Hospital Zurich, Zurich, Switzerland
s u m m a r y Keywords: Ex-utero intrapartum treatment CHAOS syndrome Congenital airway obstruction Cervical teratoma Cervical lymphangioma Congenital cystic adenomatoid malformation (CCAM)
Prenatal diagnosis has transformed the outcome of fetuses with airway obstruction. The thorough evaluation of prenatal imaging allows for categorizing fetuses with airway compromise into those who will require a special mode of delivery and those who can be delivered without any special resources. The ex-utero intrapartum treatment (EXIT) approach allows accessing the airway while the fetus is under placental support, converting a potentially catastrophic situation into a controlled one. An expert multidisciplinary team is the key to success. © 2016 Elsevier Ltd. All rights reserved.
1. Introduction Fetuses with airway obstruction at delivery are at great risk of hypoxic brain injury and mortality. The advent of prenatal diagnostic strategies galvanized the perinatal management of such fetuses. The first example of this was reported by Holinger et al. in 1985. Prenatal diagnosis of a cervical teratoma allowed for special airway equipment to be pre-emptively mobilized to the delivery room prior to cesarean delivery. Direct laryngoscopy and bronchoscopy was used to secure the airway immediately after delivery [1]. The concept of accessing an obstructed airway while keeping the fetus under placental support was first reported by Kelly et al. in 1990, in which direct laryngoscopy was performed to secure the airway [2]. A few months later, Levine et al. reported the sentinel case of a tracheostomy performed on a fetus under placental support in order to secure an airway [3]. No maternal interventions to prevent uterine contractions were performed in these reports, and the fetuses were entirely delivered from the uterus prior to airway manipulation. During the early 1990s this concept evolved until, in 1996, a team at University of California, San Francisco, described a standardized procedure called ex-utero intrapartum treatment (EXIT) [4]. They reported the reversal of a tracheal occlusion in patients with prenatally treated congenital diaphragmatic hernia.
The EXIT procedure is now the gold standard strategy for delivering fetuses with congenital airway obstruction. It permits the fetal airway to be secured in an elective, controlled manner while the fetus remains under placental support. Once adequate ventilation is secured, the fetus can be safely taken off placental support. The indications for an EXIT procedure have grown over time and now include a myriad of conditions, including cervical lymphangiomas, cervical teratomas, large congenital lung malformations, conjoined twins, and congenital high airway obstruction syndrome (CHAOS) [5e7]. Successful performance of an EXIT procedure rests on both thorough preoperative planning and the availability of a highly skilled multidisciplinary team. 2. Prenatal assessment It is of paramount importance to establish an early diagnosis in order to facilitate a prompt referral of the mother and fetus to a center proficient in performing an EXIT and fetal surgery. The prenatal evaluation of a fetus with airway obstruction includes amniocentesis and other genetic tests, if warranted, but, most importantly, a thorough assessment of the fetal anatomy with fetal three-dimensional ultrasound, fetal echocardiography and ultrafast fetal magnetic resonance imaging (Figs 1 and 2). 3. Team approach and equipment
* Corresponding author. Address: The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA. Tel.: þ1 215 510 8244. E-mail address: [email protected] (P. Laje).
The EXIT procedure can only be successful if performed by a multidisciplinary team that includes anesthesiologists, pediatric surgeons, neonatologists, maternalefetal medicine specialists,
http://dx.doi.org/10.1016/j.siny.2016.04.003 1744-165X/© 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Laje P, et al., Immediate operative management of the fetus with airway anomalies resulting from congenital malformations, Seminars in Fetal & Neonatal Medicine (2016), http://dx.doi.org/10.1016/j.siny.2016.04.003
2
P. Laje et al. / Seminars in Fetal & Neonatal Medicine xxx (2016) 1e6
fetal cardiologists, and a committed group of operating room nurses and personnel. Extensive preoperative planning, simulations, and ad-hoc team meetings are mandatory. The entire range of airway equipment needs to be sterilely available, including rigid infant-type laryngoscope handles, a set of number 0, 1 and 2 straight Miller blades, rigid ventilating bronchoscopes (sizes 2.5 and 3.0), wire-reinforced cuffless endotracheal tubes (ETTs), tracheostomy tubes, and all surgical instruments required for a neonatal tracheostomy. Once the airway is established, a sterile Mapleson circuit with a manometer and a 1 L bag is used on the sterile surgical field to help ventilate the fetus. Fetuses undergoing an EXIT procedure frequently need immediate post-EXIT surgical interventions for which, ideally, a second operating room must be readily available next to the room where the EXIT takes place. 4. Timing of delivery
Fig. 1. Cervical teratoma as seen on three-dimensional ultrasound imaging. Reprinted with permission from Lioy J, Sobol S editors. Disorders of the neonatal airway: fundamentals for practice, p. 182. © Springer, 2015.
Under ideal circumstances, a fetus with airway obstruction should reach term and be electively delivered. However, this may not be possible in some situations as the cause of airway obstruction and its effects on fetal health may dictate otherwise. For example, large cervical tumors may result in compression of the airway and the pharynx/esophagus, resulting in polyhydramnios and medically unresponsive preterm labor. When a mother carrying a fetus with airway obstruction develops signs of impending labor (such as severe recurrent polyhydramnios or shortened uterine cervix) it is crucial to perform an elective preterm EXIT at a time of day when required personnel are available. This is preferable to waiting for the fetus to reach term due to the risk of developing labor at off-hours when the resources necessary for an EXIT may not be easily available. A large published series of fetuses with cervical teratomas having undergone an EXIT reported that only 23% of the fetuses reached term [8]. 5. Ex-utero intrapartum treatment
Fig. 2. Ultra-fast prenatal magnetic resonance imaging. (A) Twin pregnancy with one fetus with a cervical teratoma (black arrow). (B) Giant cervical teratoma (white arrow) in a fetus with cystic and solid components. Reprinted with permission from Lioy J, Sobol S editors. Disorders of the neonatal airway: fundamentals for practice, p. 182. © Springer, 2015.
Undoubtedly, deep maternal general anesthesia is essential for a successful EXIT procedure, as general anesthetic drugs are the strongest uterine relaxants currently known and utero-placental gas exchange only happens if the uterus is relaxed. In order to facilitate the management of postoperative maternal pain, an epidural catheter is employed. The mother is meticulously monitored during the EXIT procedure with continuous electrocardiogram, pulse oximetry, invasive monitoring of arterial blood pressure, urinary output with a catheter, core body temperature and peripheral nerve stimulation. The combination of drugs used for induction and maintenance of anesthesia during an EXIT procedure may vary, but the principle of deep inhalational anesthesia must not change. The cornerstone from an anesthesiologist’s point of view is to maintain the fetaleplacental circulation, which requires adequate uterine relaxation and maintenance of uterine perfusion pressure. Two patients must be anesthetized for the benefit of one, and there is little margin for error [9]. The induction of maternal anesthesia is usually done with intravenous propofol (2 mg/kg) closely followed by a muscle relaxant such as succinylcholine (1 mg/kg) to facilitate a rapid endotracheal intubation. Maintenance of anesthesia is done with desflurane (5e10%) titrated to uterine tone as evaluated by direct palpation during the procedure. Vecuronium (0.1 mg/kg/dose boluses, repeated pro re nata) is used for muscle relaxation. Maternal hypotension may occur as a response to the deep general anesthesia required to facilitate uterine relaxation. This must be
Please cite this article in press as: Laje P, et al., Immediate operative management of the fetus with airway anomalies resulting from congenital malformations, Seminars in Fetal & Neonatal Medicine (2016), http://dx.doi.org/10.1016/j.siny.2016.04.003
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aggressively treated with an alpha-1-adrenergic agonist (phenylephrine) as a continuous infusion (10e200 mg/min) closely titrated during the procedure to maintain the maternal mean arterial pressure >60 mmHg. A continuous dopamine infusion may also be used. With the completion of the procedure and the clamping of the umbilical cord, uterine contraction is induced with intravenous oxytocin (50 U) administered to the mother. Methylergonovine, carboprost, and misoprostol may also be used if needed. The EXIT procedure involves a higher risk of complications for the mother than a standard cesarean section. Specifically, the risks of general anesthesia are higher than epidural anesthesia. Even more significantly, during the EXIT procedure the purposeful inhibition of uterine contractions with deep anesthesia is a set-up for uterine hemorrhage following detachment of the placenta. Whereas the average blood loss for a standard cesarean section may be 500e600 mL, EXIT procedures have been reported to have an average blood loss of >1000 mL [10,11]. The unique characteristics of anesthesia required for prolonged placental support of the fetus mandate that an anesthesiologist familiar with these procedures be involved.
tumor, the next step is rigid bronchoscopy. This technique can decompress and straighten the airway, to a certain degree, as it is advanced distally. Gentle external manipulation of a large cervical mass may help relieve some compression and deviation of the airway, aiding in bronchoscopic visualization of the airway. Rigid bronchoscopy can also be used to maneuver a wire into the distal airway that can be used as a guide for advancing an endotracheal tube (Seldinger-like technique). Rigid bronchoscopy can help to delineate the relationship of the larynx and trachea relative to a tumor should a surgical airway be required (Fig. 3). If the cervical tumor contains large cysts, decompression utilizing an ultrasound-guided percutaneous drainage during the EXIT can increase airway visualization and the chances of a successful orotracheal intubation. Pedunculated tumors obstructing the airway, such as oropharyngeal tumors (epignathus, epulis), may be resected during the EXIT procedure (Fig. 4). The EXIT procedure provides time for surgical resection and establishing a secure airway thereafter [12].
6. Exposure of the fetus during the EXIT
If laryngoscopy and bronchoscopy is unsuccessful in establishing a secure airway, such as in the case of severe macroglossia (Fig. 5), the placement of a tracheostomy is necessary. Performing a tracheostomy in this setting can be an extremely challenging procedure due to the presence of large cervical tumors (particularly cervical teratomas). Therefore, preoperative evaluation of fetal radiologic imaging, prior to the EXIT, is vital to visualize the relationship between the tumor and the airway. This essential step can save valuable intraoperative time should a surgical airway be needed [13]. Preoperative examination of fetal imaging can help predict (to a certain degree) the likelihood of a successful orotracheal intubation. Whereas solid tumors, such as teratomas, may be more aggressive, cystic tumors such as lymphatic malformations may be pliable and are usually not destructive or invasive. Cervical teratomas, as they grow, pull the trachea and lungs superiorly against the thoracic inlet. This phenomenon may result in various degrees of pulmonary hypoplasia. In contrast, pulmonary hypoplasia is not seen in patients with cervical lymphangioma [14]. In
Only the area of the fetus that is going to be operated on should be exteriorized through the hysterotomy, while the rest of the fetus must stay within the uterine cavity to maintain uterine volume and fetal temperature. This concept pertains to all EXIT and fetal surgery procedures. In cases of airway obstruction, the head, neck, upper extremities, and upper torso are exteriorized. A pulse oximeter (enclosed with aluminum foil and a Tegaderm (3M, St Paul, MN, USA)) and a 24-gauge intravenous catheter are placed using the upper extremities. Fetal vital signs are watched intraoperatively with a pulse oximeter and continuous sterile intraoperative echocardiography performed by a cardiologist who is scrubbed in with the operating team. Fetal anesthesia is achieved through the placenta, but must be supplemented with a single intramuscular dose of an opioid (fentanyl, 0.2 mg/kg), and a muscle relaxant (vecuronium, 0.1 mg/ kg) once the fetus has been exposed. Such medications (and all other drugs such as atropine, epinephrine, and calcium that are potentially needed at the time of a code) are preoperatively drawn up in sterile syringes and made ready for use on the operating table. Drugs, crystalloid solutions and blood may be given to the fetus as required through the intravenous line. Frequently the fetus requires a variety of interventions during the EXIT procedure due to alterations in vital signs. Fetal bradycardia and myocardial dysfunction are not rare. These conditions, particularly when they are acute, prompt immediate investigation. Cord compression may be the culprit and can be quickly relieved by fetal repositioning and increased amnio-infusion. Fetal cardiac dysfunction due to hypovolemia must be quickly recognized and treated with a fetal transfusion of packed red blood cells.
8. When is a tracheostomy necessary?
7. Management of the fetal airway The first intervention should always be performance of direct laryngoscopy to identify the vocal cords and fetal airway. This can be best achieved after the fetal head is exteriorized and after a shoulder roll is placed, allowing for neck extension. If the vocal cords are visible without significant obstruction from a tumor, an attempt is made to intubate the trachea employing the laryngoscope. However, if the airway is not clearly delineated with direct laryngoscopy due to deviation, compression, or invasion by a
Fig. 3. Bronchoscopy performed during an ex-utero intrapartum therapy (EXIT) procedure in a fetus with a giant cervical mass (black triangle) may help delineate critical airway anatomy. Reprinted with permission from Lioy J, Sobol S editors. Disorders of the neonatal airway: fundamentals for practice, p. 185. © Springer, 2015.
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Fig. 5. Severe macroglossia necessitating potential tracheostomy during ex-utero intrapartum therapy (EXIT) procedure.
the tumor has been removed (because the area is left with large floppy skin flaps), may be a difficult situation. Two different techniques may be employed to address this challenge. First, by tunneling a regular ETT under the skin through a skin incision lateral to the midline before entering the trachea, the ETT may be used in place of a tracheostomy tube. Second, after the trachea is dissected from the tumor, a 4e8F nasogastric (NG) tube may be threaded retrograde within the airway through a tracheostomy incision in the trachea and pulled up through the oral cavity. Next, the ETT is sutured to the NG tube tip and then the NG tube is pulled back through the neck in order to guide the ETT antegrade into the optimal position in the trachea. This technique is called retrograde intubation (Fig. 6).
Fig. 4. Oropharyngeal tumors present at birth may be life-threatening. (A) Fetus with multiple epulis originating from the upper and lower alveolar ridges. (B) Giant epignathus necessitating ex-utero intrapartum therapy (EXIT) procedure and placement of a tracheostomy. Courtesy of Alan Flake, MD; reprinted with permission from Lioy J, Sobol S editors. Disorders of the neonatal airway: fundamentals for practice, p. 186. © Springer, 2015.
our extensive experience, 53% of fetuses with cervical teratomas required a tracheostomy at the time of the EXIT, compared with only 8% of fetuses with cervical lymphangiomas [8]. To perform a tracheostomy, a transverse incision is usually made one to two fingerbreadths above the sternal notch, and extended to the side of the neck to which the airway is deviated. Once the airway is identified, tumor is dissected from the airway to relieve the compression and perform the tracheostomy at the appropriate level. The anatomy may not be as readily apparent since the carina may be located as high as the level of the sternal notch, an effect from the upward deviation of the trachea by the tumor. Ideally, the tracheostomy should be performed at the level of the second or third tracheal ring, but this is often a difficult task due to severe alteration of the anatomy. Once a tracheostomy is safely performed, securing the tracheostomy tube to any cervical structures, either while the tumor is still present (because of the mass effect) or after
Fig. 6. Retrograde intubation. A nasogastric tube (white arrow) is passed retrograde from the tracheostomy to the mouth and is used to guide the endotracheal tube (asterisk) antegrade into the airway.
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Manual ventilation is initiated on the operative field immediately after the airway is established and secured. If the fetus is <34 weeks of gestation, surfactant is administered. Additionally, if the fetus is stable, prior to clamping and dividing the umbilical cord, umbilical arterial and venous lines can be placed. When performing the EXIT procedure for a fetus with CHAOS syndrome, the diagnosis is confirmed and the proximal airway is evaluated with direct laryngoscopy and bronchoscopy. Ultimately, however, a tracheostomy is always mandatory. After securing an airway, the fetal portion of the EXIT procedure concludes and the newborn is taken to an adjoining resuscitation room. In caring for the mother, the placenta is delivered, uterine tone is quickly restored, and both the uterine and abdominal walls are closed in a similar fashion as performed in a cesarean section. If a congenital airway obstruction is present in a twin pregnancy, the healthy twin should be delivered first if possible [15]. Due to the presence of anesthetic gases from maternal exposure, immediate endotracheal intubation and respiratory support of the healthy twin is essential. 9. EXIT procedure for other airway malformations When a fetus with a giant lung mass, such as congenital cystic adenomatoid malformation (CCAM) or bronchial atresia, is anticipated to have profound respiratory insufficiency from severe mediastinal shift and compression of the healthy contralateral lung, the mode of delivery should also be an EXIT procedure. The prenatal natural history of fetal lung lesions ranges from lesions that spontaneously regress during the third trimester, to lesions that rapidly expand resulting in hydrops and in-utero demise. Large tumors may cause extreme mediastinal shift, leading to vena cava obstruction, cardiac compression, and ultimately fetal hydrops. The mass effect may also lead to relative pulmonary hypoplasia and compromised function of the remaining lung [16]. The CCAM volume ratio (CVR) has been used to track tumor growth and regression during gestation. Elevated CVR (>1.6) at presentation correlates with the development of hydrops, need for fetal intervention, need for ventilatory support, need for extracorporeal membrane oxygenation (ECMO), length of postnatal hospital stay, and survival [17]. In a series of nine patients, the EXIT procedure allowed for controlled resection of large fetal lung lesions at delivery, avoiding acute respiratory decompensation related to mediastinal shift, air trapping, and compression of normal lung. Overall survival after EXIT for lung mass resection was 89%. The average time on placental bypass was 65 min. Veno-arterial ECMO was used in four neonates for persistent pulmonary hypertension postnatally. During the EXIT procedure, the airway is safely secured via endotracheal intubation and the lung mass is resected with the fetus supported by placental circulation [18]. If the mediastinal shift is severe, but not extreme, the fetus can be delivered by the “cesarean section-to-resection” strategy, in which the fetus is intubated immediately after the cesarean section and the lung resection is done immediately after that. 10. Conclusions Delivering a fetus with airway obstruction without the required resources invariably results in death or permanent brain damage. The EXIT procedure, albeit complex, allows access to the fetal airway in a controlled and secure manner while the fetus is still under placental support. A skilled multidisciplinary team that performs fetal surgery on a regular basis is the key to success.
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Practice points The EXIT procedure is the gold standard strategy for delivering a fetus with congenital airway obstruction as it permits the fetal airway to be secured in an elective, controlled manner while the fetus remains under placental support. The EXIT procedure can only be successful if performed by a multidisciplinary team that includes anesthesiologists, pediatric surgeons, neonatologists, maternal fetal medicine specialists, fetal cardiologists, and a group of operating room nurses and personnel. When a mother carrying a fetus with airway obstruction develops signs of impending labor it is crucial to perform an elective preterm EXIT at a time of day when required personnel are available. Tracheostomy is necessary if laryngoscopy and bronchoscopy during the EXIT procedure is unsuccessful in establishing an airway in a fetus with congenital airway obstruction.
Research directions The investigation and application of EXIT procedures for other fetal pathologies. Investigating how maternal and fetal morbidity may be further decreased in performing an EXIT procedure.
Conflict of interest statement None declared. Funding sources None. References [1] Holinger LD, Birnholz JC, Bruce DR, Rabin DN. Management of an infant with prenatal ultrasound diagnosis of upper airway obstruction. Int J Pediatr Otorhinolaryngol 1985;10:263e70. [2] Kelly MF, Berenholz L, Rizzo KA, Greco R, Wolfson P, Zwillenberg DA. Approach for oxygenation of the newborn with airway obstruction due to a cervical mass. Ann Otol Rhinol Laryngol 1990;99(3 Pt 1):179e82. [3] Levine AB, Alvarez M, Wedgwood J, Berkowitz RL, Holzman I. Contemporary management of a potentially lethal fetal anomaly: a successful perinatal approach to epignathus. Obstet Gynecol 1990;76:962e6. [4] Harrison MR, Adzick NS, Flake AW, VanderWall KJ, Bealer JF, Howell LJ, et al. Correction of congenital diaphragmatic hernia in utero VIII: response of the hypoplastic lung to tracheal occlusion. J Pediatr Surg 1996;31:1339e48. [5] Hedrick HL. Ex utero intrapartum therapy. Semin Pediatr Surg 2003;12: 190e5. [6] Liechty KW. Ex-utero intrapartum therapy. Semin Fetal Neonatal Med 2010;15:34e9. [7] Lim FY, Crombleholme TM, Hedrick HL, Flake AW, Johnson MP, Howell LJ, et al. Congenital high airway obstruction syndrome: natural history and management. J Pediatr Surg 2003;38:940e5. [8] Laje P, Johnson MP, Howell LJ, Bebbington MW, Hedrick HL, Flake AW, et al. Ex utero intrapartum treatment in the management of giant cervical teratomas. J Pediatr Surg 2012;47:1208e16. [9] Lin EE, Tran KM. Anesthesia for fetal surgery. Semin Pediatr Surg 2013;22: 50e5.
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Please cite this article in press as: Laje P, et al., Immediate operative management of the fetus with airway anomalies resulting from congenital malformations, Seminars in Fetal & Neonatal Medicine (2016), http://dx.doi.org/10.1016/j.siny.2016.04.003