Anesthetic considerations of EXIT procedure: A case report.

The ex-utero intrapartum treatment (EXIT) is a rare surgical procedure performed in cases of expected postpartum fetal airway obstruction. This procedure technique lies in a safe establishment of a patent airway during labor in anticipation of a critical respiratory event, without the interruption of maternal-fetal circulation. Anesthetic management in the EXIT procedure is substantially different from that of the standard cesarean delivery and its main goals include uterine relaxation, fetal anesthesia, and placental blood flow preservation. We report the first case of an EXIT procedure performed on a fetus with a prenatal diagnosis of multiple oral masses at King Khalid University Hospital, Riyadh, Saudi Arabia.

Fetal Laryngoscopy and Endoscopic Tracheal Intubation to Avoid ex utero Intrapartum Treatment in the Management of Fetuses with Suspected Airway Obstruction.

INTRODUCTION: Large congenital neck tumors can cause neonatal death due to airway obstruction. The aim of this study was to report outcomes of the first cohort of fetuses with neck masses and suspected airway obstruction managed with fetal laryngoscopy (FL) and fetal endoscopic tracheal intubation (FETI) to secure fetal airways and avoid ex utero intrapartum treatment (EXIT) procedure. METHODS: A prospective observational cohort of consecutive fetuses with neck masses that were candidates for an EXIT procedure due to suspicion of laryngeal and/or tracheal occlusion on ultrasonographic (US) or magnetic resonance imaging (MRI) examination were recruited for FL in a tertiary referral center in Queretaro, Mexico. FETI was performed if the obstruction was confirmed by FL. Maternal and perinatal outcomes were evaluated. RESULTS: Between January 2012 and March 2023, 35 cases with neck masses were evaluated. Airway obstruction was suspected in 12/35 (34.3%), either by US in 10/35 (28.6%) or by fetal MRI in 2/35 (5.7%). In all cases, FL was successfully performed at the first attempt at a median gestational age (GA) of 36+5 (range, 33+5-39+6) weeks+days, with a median surgical time of 22.5 (12-35) min. In 4 cases, airway patency was confirmed during FL and an EXIT procedure was avoided. In 8/12 cases (66.7%), airway obstruction was confirmed during fetoscopy and FETI was successfully performed at a median GA of 36+3 (33+2-38+5) weeks+days, with a median surgical time of 25.0 (range, 12-45) min. No case required an EXIT procedure. All patients underwent conventional cesarean delivery with no maternal complications and all neonates were admitted to the neonatal intensive care unit with a correctly positioned endotracheal tube (ETT) immediately after delivery. Three neonatal deaths (37.5%) were reported due to postnatal unplanned extubation, failed ETT replacement, and tumoral bleeding. CONCLUSION: In fetuses with neck masses and suspected airway obstruction, FL and FETI are feasible and could replace EXIT procedures with good maternal and perinatal outcomes.

Fetal Endoscopic Tracheal Intubation: Modification of the Fetal Endoscopic Tracheal Intubation Procedure to Establish an Airway in a Fetus with a Congenital Cervical Teratoma.

INTRODUCTION: FETI is a technique where the fetal airway is secured in-utero via intubation by percutaneous endoscopic fetal tracheoscopy under ultrasound guidance. FETI has been described in large fetal neck masses with anatomical airway compression as a feasible airway management strategy and a potential alternative to an EXIT procedure in select cases. CASE PRESENTATION: This report describes the use of a modified FETI procedure under continuous fetoscopic and ultrasound guidance, in a fetus with a large cervical teratoma causing airway displacement and compression. Following the FETI procedure, an uncomplicated caesarean section was performed. The endotracheal tube was in place at the time of birth, and a patent airway was confirmed. CONCLUSION: The modified FETI procedure described in this report represents another technique that can be used to establish an airway in fetuses with challenging upper airway anatomy, potentially mitigating the risks associated with an EXIT procedure.

Neuraxial anesthesia in ex utero intrapartum therapy for parturients with fetal congenital diaphragmatic hernia: a prospective observational study.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is characterized by defects in the fetal diaphragm and thoracic herniation of the abdominal viscera. The ex utero intrapartum treatment (EXIT) procedure is used to establish the fetal airway while on placental support. These EXIT procedures are commonly performed under general anesthesia, which increases maternal bleeding and the risk of insufficient placental perfusion subsequently. This study investigated the feasibility of performing neuraxial anesthesia for the EXIT procedure for fetal congenital diaphragmatic hernia to improve outcomes. METHODS: Parturients with fetal CDH who underwent an EXIT procedure between January 2019 and May 2021 in our institution were recruited. Variables evaluated included gestational age, surgical time, intra-operative blood loss, peri-operative hemoglobin, maternal complications, fetal lung-to-head ratio, time on placental bypass, and postnatal outcome. RESULTS: Twenty-two cases were included. All procedures were performed under neuraxial anesthesia. The median gestational age at the time of the EXIT procedure was 37 weeks. The median estimated blood loss was 200 mL. There was no report of an adverse maternal event. The placental bypass time was 142.9 ±â€¯72.6 s, and access to the airway was successfully established within the bypass time. Twenty-one neonates reached an Apgar score of 9 at 5 min. In the first two hours after birth, the average pH of neonatal peripheral arterial blood was 7.35 ±â€¯0.07 (n=19), and lactate level 1.85 ±â€¯0.71 mmol/L (n=19). CONCLUSIONS: In the EXIT procedure to establish an airway for fetal CDH, neuraxial anesthesia proved a feasible technique for maternal anesthesia.

EXIT-to-airway: Fundamentals, prenatal work-up, and technical aspects.

Ex-utero intrapartum treatment (EXIT) is a delivery strategy developed to manage a variety of prenatally diagnosed conditions in the transition to newborn life. This procedure allows control and provides time for intervention in otherwise life-threatening malformations, such as congenital upper airway obstructions. EXIT-to-airway has changed the outcome of fetuses with these anomalies. The main purpose of this intervention is to improve the safety of establishing a reliable airway at birth. Maximal but controlled uterine relaxation to maintain feto-maternal perfusion and thus gas exchange, while keeping the fetal and maternal well-being are the paradigms of any type of EXIT. The most important aspect of fetal airway management is to consolidate a highly trained, well-coordinated, multidisciplinary team that is prepared for every contingency. A comprehensive prenatal assessment, including ultrasound, fetal echocardiogram, fetal MRI, and genetic testing is imperative for patient selection. Extensive preoperative planning, ad-hoc team meetings, and surgical simulations for challenging cases are critical strategies to achieve the best outcomes. This article outlines the prenatal work-up, decision making, technical aspects, and principles for a successful EXIT-to-airway procedure.

Calcium-Sensing Receptor Contributes to Hyperoxia Effects on Human Fetal Airway Smooth Muscle.

Supplemental O2 (hyperoxia), necessary for maintenance of oxygenation in premature infants, contributes to neonatal and pediatric airway diseases including asthma. Airway smooth muscle (ASM) is a key resident cell type, responding to hyperoxia with increased contractility and remodeling [proliferation, extracellular matrix (ECM) production], making the mechanisms underlying hyperoxia effects on ASM significant. Recognizing that fetal lungs experience a higher extracellular Ca2+ ([Ca2+]o) environment, we previously reported that the calcium sensing receptor (CaSR) is expressed and functional in human fetal ASM (fASM). In this study, using fASM cells from 18 to 22 week human fetal lungs, we tested the hypothesis that CaSR contributes to hyperoxia effects on developing ASM. Moderate hyperoxia (50% O2) increased fASM CaSR expression. Fluorescence [Ca2+]i imaging showed hyperoxia increased [Ca2+]i responses to histamine that was more sensitive to altered [Ca2+]o, and promoted IP3 induced intracellular Ca2+ release and store-operated Ca2+ entry: effects blunted by the calcilytic NPS2143. Hyperoxia did not significantly increase mitochondrial calcium which was regulated by CaSR irrespective of oxygen levels. Separately, fASM cell proliferation and ECM deposition (collagens but not fibronectin) showed sensitivity to [Ca2+]o that was enhanced by hyperoxia, but blunted by NPS2143. Effects of hyperoxia involved p42/44 ERK via CaSR and HIF1α. These results demonstrate functional CaSR in developing ASM that contributes to hyperoxia-induced contractility and remodeling that may be relevant to perinatal airway disease.

Ex-Utero Intrapartum Treatment (EXIT): indications and outcome in fetal cervical and oropharyngeal masses.

BACKGROUND: The "Ex-Utero Intrapartum Treatment" (EXIT) procedure allows to ensure fetal airway before completion of delivery and umbilical cord clamping while keeping uteroplacental circulation. Airway obstruction in fetal oropharyngeal and cervical masses can be life-threatening at birth. In those situations, controlled access to fetal airway performed by a trained multidisciplinary team allows safe airway management, while feto-maternal circulation is preserved. We aim to review the indications and outcome of the EXIT procedure in a case series of fetal cervical and oropharyngeal masses. METHODS: We have carried out a retrospective review of all patients with fetal cervical and oropharyngeal masses who underwent an EXIT procedure between 2008 and 2019. Variables evaluated included indication for EXIT, ultrasound and MRI findings, the need of amnioreduction, gestational age at EXIT, birth weight, complications, operative time, survival rate, pathological findings, and postnatal evolution. Five patients are included in this series. One additional case has already been published. RESULTS: The diagnosis were cervical teratoma (n = 1), epulis (n = 1) and lymphangioma (n = 3). Polyhydramnios was present in 2 patients, requiring amnioreduction in one of them. Mean gestational age at EXIT was 36-37 weeks (range, 34-38 weeks). Median EXIT time in placental support was 9 min (range, 3-22 min). Access to airway was successfully established in EXIT in all cases. All children born by EXIT are currently healthy and without complications. CONCLUSION: The localization and characteristics of the mass, its relationship to the airway, and the presence of polyhydramnios seem to be major factors determining indications for EXIT and clinical outcome.

Hydrogen sulfide, oxygen, and calcium regulation in developing human airway smooth muscle.

Preterm infants can develop airway hyperreactivity and impaired bronchodilation following supplemental O2 (hyperoxia) in early life, making it important to understand mechanisms of hyperoxia effects. Endogenous hydrogen sulfide (H2 S) has anti-inflammatory and vasodilatory effects with oxidative stress. There is little understanding of H2 S signaling in developing airways. We hypothesized that the endogenous H2 S system is detrimentally influenced by O2 and conversely H2 S signaling pathways can be leveraged to attenuate deleterious effects of O2 . Using human fetal airway smooth muscle (fASM) cells, we investigated baseline expression of endogenous H2 S machinery, and effects of exogenous H2 S donors NaHS and GYY4137 in the context of moderate hyperoxia, with intracellular calcium regulation as a readout of contractility. Biochemical pathways for endogenous H2 S generation and catabolism are present in fASM, and are differentially sensitive to O2 toward overall reduction in H2 S levels. H2 S donors have downstream effects of reducing [Ca2+ ]i responses to bronchoconstrictor agonist via blunted plasma membrane Ca2+ influx: effects blocked by O2 . However, such detrimental O2 effects are targetable by exogenous H2 S donors such as NaHS and GYY4137. These data provide novel information regarding the potential for H2 S to act as a bronchodilator in developing airways in the context of oxygen exposure.

EXIT (ex utero intrapartum treatment) surgery for the management of fetal airway obstruction: A systematic review of the literature.

PURPOSE: To provide a comprehensive overview of the perinatal and maternal outcomes of fetuses undergoing EXIT surgery for the management of fetal airway obstruction secondary to cervical or oral tumors. METHODS: A comprehensive search from inception to September 2018 was conducted on databases including MEDLINE, EMBASE, Cochrane Library and LILACS. All studies that reported an EXIT surgery in singleton were considered eligible. A descriptive analysis was performed. RESULTS: Out of the 250 full-text study reports, 120 articles reporting 235 cases of EXIT surgery were included. EXIT surgery was performed at 35.1 weeks of gestation on average. The most frequent diagnosis was teratoma (46.4%, n = 109/235). There were 13 adverse maternal events, and the most frequent one was postpartum hemorrhage (4.7%, n = 11/235). No maternal death was reported. Fetal and neonatal death occurred in 17% (40/235) of the cases. There were 29 adverse fetal events (12.2%), and the most frequent one was the failure of intubation or tracheostomy (3.4%, n = 8/235). CONCLUSION: EXIT surgery could be considered for the management of an oral or cervical tumor that's highly suspicious of blocking the fetal airway. This systematic review reports that EXIT surgery poses substantial risks of maternal and fetal adverse events, including neonatal death. LEVEL OF EVIDENCE: IV case series with no comparison group.

In utero Fetal Intubation for a Large Neck Mass: A Minimally Invasive EXIT Option.

Fetuses with obstructive neck and orofacial lesions have been delivered via an ex utero intrapartum treatment (EXIT) procedure to facilitate securement of the airway while on placental circulation. Pregnancy-related cardiovascular changes and technical issues unique to an EXIT procedure increase fetal and maternal risks relative to a standard cesarean section. In order to circumvent such issues, fetal endoscopic intubation has been proposed. We report a case of a fetus with a large neck mass (mixed solid and multiloculated cystic lesion measuring 9.2 × 5.3 × 8.5 cm, neck hyperextension, protruding tongue, and serial gagging movements) that was successfully intubated in utero and delivered at 36 weeks and 0 days via standard cesarean section, thereby avoiding an EXIT procedure. The risks, benefits, and technical issues of in utero tracheal intubation are reviewed.

Fetal Evaluation and Airway Management.

Congenital causes of airway obstruction once noted at birth are now diagnosed prenatally. The adoption of ex utero intrapartum treatment has allowed for planned airway stabilization on placental support, dramatically decreasing the incidence of hypoxic injury or peripartum demise related to neonatal airway obstruction. Airway access is gained either through laryngoscopy, bronchoscopy, or a surgical airway. In complete airway obstruction, primary resection of the obstructing lesion may be performed before completion of delivery. This article reviews the current and emerging methods of fetal evaluation, indications for ex utero intrapartum treatment, and provides a detailed description of the procedure and necessary personnel.

MicroRNA-874 inhibits TNF-α-induced remodeling in human fetal airway smooth muscle cells by targeting STAT3.

Pro-inflammatory cytokines-induced airway remodeling was a significant feature of asthma disease. The aim of the present study was to explore the functional significance of miR-874 in tumor necrosis factor (TNF)-α-treated human fetal airway smooth muscle (fASM) cells. Here, we found that TNF-α treatment significantly down-regulated the expression of miR-874 in fASM cells. MiR-874 overexpression markedly inhibited cell viability and migration, suppressed the expression of PCNA and Ki67, reduced the expression of collagen I and collagen III, decreased the expression and activity of matrix metalloproteinase (MMP)-9 and MMP-2, and induced an obvious elevation of tissue inhibitors of metalloproteinases (TIMPs). In addition, the increased production of interleukin (IL)-6, IL-8 and eotaxin induced by TNF-α were significantly inhibited by miR-874 overexpression. Signal transducers and activators of transcription (STAT) 3 was identified as a direct target of miR-874, and STAT3 overexpression partly reversed the protective effects of miR-874 against TNF-α-induced airway remodeling. Overall, these findings demonstrate that miR-874 inhibits TNF-α-induced remodeling in human fASM cells at least in part by targeting STAT3.

The ex utero intrapartum treatment (EXIT) procedure: application of a new therapeutic paradigm.

The ex utero intrapartum treatment (EXIT) procedure is a term given to a technique that can transform a potentially fatal neonatal emergency to a controlled intervention with an improved outcome. It has revolutionised the care of prenatally diagnosed congenital malformations in which severe upper airway obstruction is anticipated. An extended period of utero-placental circulation can be utilised to avoid profound cardiopulmonary compromise. Its therapeutic applications have been broadened to include fetuses with congenital diaphragmatic hernia after tracheal plugging, high-risk intrathoracic masses, severe cardiac malformations and conjoined twins. It requires the co-ordination of a highly skilled and experienced multidisciplinary team. The recent enthusiasm for the EXIT procedure needs to be balanced against maternal morbidity. Specific indications and guidelines are likely to be refined as a consequence of ongoing advances in fetal intervention and antenatal imaging.