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

BackgroundCongenital 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.MethodsParturients 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.ResultsTwenty-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 ± 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 ± 0.07 (n=19), and lactate level 1.85 ± 0.71 mmol/L (n=19).ConclusionsIn the EXIT procedure to establish an airway for fetal CDH, neuraxial anesthesia proved a feasible technique for maternal anesthesia.     

The ex utero intrapartum therapy procedure for high-risk fetal lung lesions

Background

Indications for the ex utero intrapartum therapy (EXIT) procedure have expanded to include any fetal anomaly in which resuscitation of the neonate may be compromised.

Methods

We reviewed the medical records of 9 patients after resection of lung lesions during the EXIT procedure.

Results

The mean gestational age at EXIT procedure was 35.4 weeks. All lung masses maintained large sizes late into gestation with mean mass volume/head circumference ratio of 2.5 at presentation and 2.2 at EXIT. Seven of 9 fetuses demonstrated hydropic changes (n = 6) and/or polyhydramnios (n = 5), and underwent prenatal intervention including thoracentesis, thoracoamniotic shunt placement, amnioreduction, and/or betamethasone administration. Overall survival after EXIT for lung mass resection was 89%. The average time on placental bypass was 65 minutes. Postnatal complications included reoperation for air leak (n = 1), reoperation for bleeding (n = 1), and death from sepsis and prematurity (n = 1). Venoarterial extracorporeal membrane oxygenation was used in 4 neonates for persistent pulmonary hypertension. Maternal prenatal complications included polyhydramnios (n = 5), preterm labor (n = 4), and chorioamnionitis (n = 1). One mother required perioperative blood transfusion.

Conclusion

The EXIT procedure allows 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.     

Perinatal management of congenital oropharyngeal tumors: The ex utero intrapartum treatment (EXIT) approach

Purpose

To present our experience in the perinatal management of fetuses with large oropharyngeal tumors by ex utero intrapartum treatment (EXIT).

Methods

We performed a retrospective chart review of all patients with congenital oropharyngeal tumor who underwent an EXIT procedure between May 2006 and June 2012.

Results

Four patients were included in the series, three females and one male. The diagnoses were epignathus (n = 2) and congenital epulis (n = 2). Three EXITs were done at term and one at late preterm due to premature rupture of membranes. Median maternal time under anesthesia was 185 min (range: 166–281) and median maternal operative time was 99 min (range: 85–153). Median maternal blood loss was 550 ml (range: 350–2000); one mother required a blood transfusion. Mean maternal hospital stay was 4 days. Median hysterotomy-to-cord clamp time was 24 min (range: 18–66). Mean fetal birth weight was 2.7 kg (range: 2.4–3). The airway was successfully accessed and secured under placental circulation in all cases. In the two patients with congenital epulis the tumors were resected at the base of their pedicles and the airway accessed via direct laryngoscopy before the umbilical cord was clamped. One patient with epignathus underwent a retrograde tracheal intubation under placental circulation and had the tumor resected thereafter. The second patient with epignathus had a tracheostomy done under placental circulation and then had tumor debulking immediately after the EXIT. The maternal morbidity was minimal and there were no mortalities.

Conclusions

We conclude that the EXIT procedure is the ideal delivery strategy for fetuses with prenatally diagnosed oropharyngeal tumors and potential airway obstruction at birth. Patients with prenatally diagnosed oropharyngeal tumors should be promptly referred to a fetal treatment center with a dedicated multidisciplinary team and EXIT capabilities.     

Spiral electrode for continuous fetal heart rate monitoring during in-utero myelomeningocele repair

Continuous fetal hemodynamic monitoring during in-utero surgery is desirable, but it is often not feasible without intermittent interruption. We report the use of a fetal spiral electrode for continuous heart rate monitoring during fetal myelomeningocele repair. Fetal echocardiography and a fetal spiral electrode were used to monitor fetal heart rate during in-utero repair at 25 weeks’ gestation. We observed good agreement between echocardiographic and spiral electrode heart rate measurements. Using the Bland-Altman approach, the mean (SD) difference between measurements was 1.8 (3.5) beats per minute with limits of agreement of −5.3 to 8.8 beats per minute. This case illuminates a potential role for a fetal spiral electrode as a real-time adjunct in fetal interventions.     

Ex utero intrapartum treatment with extracorporeal membrane oxygenation for severe congenital diaphragmatic hernia

Purpose

The purpose of this study was to determine whether ex utero intrapartum treatment with extracorporeal membrane oxygenation (EXIT to ECMO) is a reasonable approach for managing patients antenatally diagnosed with severe congenital diaphragmatic hernia (CDH).

Methods

A 6-year retrospective review was performed on fetuses with severe CDH (liver herniation and a lung/head ratio <1.4, percentage of predicted lung volume <15, and/or congenital heart disease). Fourteen of the patients underwent EXIT with a trial of ventilation. Fetuses with poor preductal oxygen saturations despite mechanical ventilation received ECMO before their delivery. Maternal-fetal outcomes were analyzed.

Results

There were no maternal-reported complications. Three babies passed the ventilation trial and survived, but 2 of them required ECMO within 48 hours. The remaining 11 fetuses received ECMO before their delivery. Overall survival after EXIT-to-ECMO was 64%. At 1-year follow-up, all survivors had weaned off supplemental oxygen, but 57% required diuretics and/or bronchodilators.

Conclusion

This is the largest reported experience using EXIT to ECMO in the management of severe CDH. The EXIT-to-ECMO procedure is associated with favorable survival rates and acceptable pulmonary morbidity in fetuses expected to have a poor prognosis under conventional management.     

Management of fetal mediastinal teratoma

Background/Purpose

Mediastinal teratomas are rare congenital germ cell tumors that prenatally can compress mediastinal structures and cause hydrops. Two possible presentations of massive fetal mediastinal teratoma include hydrops leading to fetal demise, or fetal esophageal and airway compression causing late-gestation polyhydramnios and preterm labor. The authors present 2 cases of fetal mediastinal teratoma that illustrate successful strategies for either of these presentations.

Methods

A 37-year-old woman carrying a fetus with a mediastinal mass and secondary hydrops at 23 weeks of gestation underwent in utero resection of the mass. Delivery was by cesarean delivery at 25 weeks because of preterm labor. A 24-year-old mother carrying a fetus with a mediastinal mass and severe polyhydramnios at 36 weeks of gestation underwent an ex utero intrapartum therapy procedure for establishment of an airway and tumor resection on uteroplacental support.

Results

These strategies resulted in physiologic improvement in the first case and controlled resection and resuscitation in the second. The first patient had significant sequelae of prematurity including bronchopulmonary dysplasia but is currently well at 9 months of age. The second patient is well at 1 year of age.

Conclusions

Massive fetal mediastinal teratoma can result in fetal or neonatal mortality by a variety of mechanisms. Optimal prenatal and perinatal management is required to salvage fetuses compromised by this lesion.     

Ex utero intrapartum treatment with placement on extracorporeal membrane oxygenation for fetal thoracic masses

Purpose

We describe our experience with fetuses diagnosed with life-threatening chest masses who were delivered by ex utero intrapartum treatment with placement on extracorporeal membrane oxygenation (EXIT-to-ECMO).

Methods

The first fetus presented with a cystic mediastinal mass and enlarging echogenic lungs. Bronchoscopic evaluation during ex utero intrapartum treatment (EXIT) revealed complete airway obstruction secondary to a carinal bronchogenic cyst. The second fetus presented with a massive left congenital cystic adenomatoid malformation. The EXIT procedure was performed because of significant mediastinal shift, severe compression of the normal lung parenchyma, and signs of fetal distress.

Results

In both cases, extracorporeal membrane oxygenation (ECMO) was initiated while on placental support. The fetuses were then delivered, and a definitive resection of their thoracic lesions was successfully performed. There were no major perioperative complications. Both children made expedient recoveries without significant cardiopulmonary sequelae.

Conclusion

To our knowledge, this is the first report describing the successful use of EXIT-to-ECMO as a bridge to definitive resection of large chest masses diagnosed in utero. EXIT-to-ECMO is a novel and effective management strategy for stabilizing patients with profound respiratory compromise secondary to congenital thoracic lesions.     

Airway management for neonates requiring ex utero intrapartum treatment (EXIT)

In utero congenital malformations in the fetus can occasionally lead to an obstructed airway at birth accompanied by hypoxic injury or peripartum demise, without intervention. Ex utero intrapartum treatment (EXIT) may help reduce morbidity and mortality associated with challenging airways by providing extra time on uteroplacental circulation to secure the airway. Meticulous preparation and planning are crucial for this procedure. Many different types of congenital malformations can result in a difficult airway, but there is no correlation between specific malformations and a required type of airway intervention. Based on our experience and literature review, an airway process flow diagram has been created to help assist teams in decision‐making for airway intervention in a neonate during the EXIT procedure. The management of the airway in this scenario involves additional unique considerations that accompany handling a partially delivered newborn in the uterine environment. Extensive preparation and team rehearsal are essential to the success of this procedure.     

Remifentanil-nitroglycerin combination as an anesthetic support for ex utero intrapartum treatment (EXIT) procedure

A 21 year old healthy parturient was diagnosed as having a fetus with micrognathia. She was scheduled for an ex-utero intrapartum treatment (EXIT) procedure. General anesthesia consisted of remifentanil, nitrous oxide, and midazolam. Intravenous nitroglycerin was used for uterine relaxation. This technique offered hemodynamic stability and provided uterine relaxation that may be rapidly terminated. For the fetus, it provided excellent transplacental anesthesia. Supplemental direct fetal anesthesia is recommended to prevent the rapid decline of analgesia/anesthesia that occurs after placental separation.     

The ex utero intrapartum treatment procedure: Looking back at the EXIT

Purpose

The ex utero intrapartum treatment (EXIT) procedure was developed originally for management of airway obstruction after fetal surgery, and indications have continued to expand for a variety of fetal anomalies. The authors review their single-institution experience with EXIT.

Methods

Retrospective review of all patients who underwent an EXIT procedure from 1993 to 2003 (n = 52) was performed. Variables evaluated include indication for EXIT, gender, gestational age at EXIT, birth weight, maternal blood loss, operative complications, operative time, and survival rate. Technique, personnel, and anesthesic management were reviewed.

Results

Long-term follow-up was available for all patients. Fifty-one of 52 patients were born alive; currently, 27 of 52 patients (52%) are alive. All deaths have been in patients with congenital diaphragmatic hernia. Forty-five patients underwent EXIT for reversal of tracheal occlusion for congenital diaphragmatic hernia. Of these patients, 30 underwent tracheal clip removal. Two patients had repair of tracheal injury from clipping at EXIT. Fifteen patients underwent bronchoscopy and tracheal balloon removal. Five patients underwent EXIT procedure for neck masses. Tracheostomy was performed in 3 of these patients. One patient was intubated successfully, and 1 patient underwent resection of the neck mass while on placental support. Two patients underwent EXIT procedure and tracheostomy for congenital high-airway obstruction syndrome. Average gestational age at delivery was 31.95 ± 2.55 weeks. Average birth weight was 1,895 ± 653 g. Average maternal blood loss was 970 ± 510 mL. Average operating time on placental support was 45 ± 25 minutes with a maximum of 150 minutes.

Conclusions

EXIT procedures can be performed with minimal maternal morbidity and with good outcomes. It is an excellent strategy for establishing an airway in a controlled manner, avoiding “crash” intubation or tracheostomy. Longer procedures on placental support allowing for definitive management of neck masses and airway obstruction have been realized. EXIT procedures have evolved from an adjunct to fetal surgery to a potentially life-saving procedure in fetuses with airway compromise at birth.     

Early delivery as an alternative management strategy for selected high-risk fetal sacrococcygeal teratomas

Background

Large, prenatally diagnosed sacrococcygeal teratomas (SCTs) present a formidable challenge because of their unpredictable growth and propensity for complications. In our experience, even with aggressive serial imaging, many fetuses have died under a policy of “watchful waiting.” We propose “early delivery” as the best option for selected cases of high-risk fetal SCT.

Methods

The medical charts of all fetuses with SCT followed up at our institution and delivered before 32 weeks of gestation were reviewed for radiologic findings, fetal interventions, delivery information, perinatal inpatient course, and autopsy or discharge report.

Results

Between 1996 and 2009, excluding those that underwent fetal surgery, 9 patients with fetal SCT were delivered before 32 weeks of gestation. Four had type I tumors, and 5 had type II tumors. Of the 9 fetuses, 4 survived the neonatal period. The only surviving patient delivered before 28 weeks underwent an ex utero intrapartum therapy procedure.

Conclusions

A significant number of pregnancies complicated by high-risk SCT will manifest signs of fetal or maternal decompensation, or both, between 27 and 32 weeks of gestation. In the absence of fulminant hydrops, preemptive early delivery can be associated with surprisingly good outcomes in appropriately selected fetuses with high-risk SCT.     

A case of laryngeal atresia (congenital high airway obstruction syndrome) with chromosome 5p deletion syndrome rescued by ex utero intrapartum treatment

The authors report a case of laryngeal atresia (congenital high airway obstruction syndrome [CHAOS]) that was diagnosed prenatally. The patient underwent successfully tracheostomy by ex utero intrapartum treatment (EXIT). The fetal ultrasonography and magnetic resonance imaging MRI showed a typical CHAOS pattern with expanded hyperechogenic lungs, inverted diaphragms, and a dilated trachea. Recently, 3 cases of prenatally diagnosed CHAOS were reported to be treated successfully by EXIT. The clinical manifestation and course of this case was not similar to these 3 cases. The 3 previous patients did not fare as well during gestation and were delivered earlier than that in our case. In our case, fetal hydrops was seen at 23 gestational weeks, but it gradually subsided and disappeared at 30 gestational weeks. The fetus was stable and well. After delivery at 39 weeks, the baby received respiratory assistance by ventilator assistance. After 3 days, she could breath well on her own. The patient also had chromosome 5p deletion syndrome and perineal groove. More experience in treating CHAOS cases with EXIT to fully estimate its clinical course and prognosis is needed.     

Intraoperative fetal heart rate monitoring during emergency neurosurgery in a parturient

Malignant brain tumors during pregnancy are rare, and these patients seldom require immediate surgical intervention. A 27-year-old pregnant woman underwent emergency craniotomy. Anesthesia was induced with intravenous thiopental-fentanyl; it was maintained with isoflurane in oxygen and continuous intravenous remifentanil infusion. We used full stomach precautions but omitted succinylcholine for fear of increasing the intracranial pressure during induction of anesthesia. To detect fetal hypoxia and the effects of anesthesia on fetal hemodynamics, the fetal heart rate (FHR) was monitored using a fetal Doppler ultrasonography unit fixed to the mother's abdominal wall. Intraoperative and recovery periods were uneventful. Use of an isoflurane and remifentanil combination provided stable hemodynamics with adequate arterial blood pressure to avoid uterine hypoperfusion and fetal hypoxia. In this case, using FHR monitoring we found that craniotomy can be performed safely under isoflurane/remifentanil based-general anesthesia during the second trimester of pregnancy.     

Differential risk for neonatal surgical airway intervention in prenatally diagnosed neck masses

Purpose

We aimed to identify risk factors for neonatal surgical airway intervention among fetuses with prenatally diagnosed cervical masses.

Methods

An 8-year retrospective review identified 23 consecutive patients with a prenatal diagnosis of a neck mass, managed at a single tertiary center. Variables analyzed included anticipated diagnosis, extent of the mass, need for any surgical airway intervention in the neonatal period, final histopathology data, and survival. Statistical analysis was based on the Fisher and Fisher-Freeman-Halton exact tests (significance set at P ≤ .05) and exact 95% confidence intervals for risk differences.

Results

Eight patients underwent termination of pregnancy or were lost to follow-up. The imaging-based prenatal diagnosis was confirmed postnatally in 93% (14/15) of the remaining patients. Final diagnoses included lymphatic malformation (8), teratoma (6), and esophageal duplication (1). Teratomas were associated with a significantly higher risk for neonatal airway intervention than lymphatic malformations (67% vs 11%, P = .02). The majority of such procedures were performed under ex utero intrapartum treatment. Survival was 93% (14/15).

Conclusions

Cervical teratomas are significantly more likely to demand surgical airway intervention in the neonate, typically under ex utero intrapartum treatment, than cervical lymphatic malformations. These findings should be considered in the prenatal counseling for fetal cervical masses.     

Fetal lung interstitial tumor: a cause of late gestation fetal hydrops

Most fetal lung masses present by mid gestation, grow during the canalicular phase of lung development (18-26 weeks of gestation), and plateau in growth or shrink after 26 weeks of gestation. We describe the unique case of a fetal lung mass presenting at 37 weeks of gestation with hydrops and fetal heart failure. The late growth of this lesion and resultant hydrops prompted resection as part of the ex utero intrapartum treatment. Histopathology revealed a rare, recently described fetal lung interstitial tumor. This case demonstrates that a subset of fetal lung masses may continue to grow later in gestation and emphasizes the need for late gestation imaging and close follow-up in this patient cohort.     

Airway management during an EXIT procedure for a fetus with dysgnathia complex

Nonsyndromal dysgnathia is a rare disorder with a probable genetic basis characterized by a hypoplastic or absent mandible (agnathia), microstomia, microglossia, and ear anomalies secondary to a defect in the ventral portion of the first branchial arch caused by defective neural crest migration or proliferation. Dysgnathic newborn infants often suffer fatal respiratory failure from airway obstruction. Nineteen children with isolated dysgnathia complex are described in the literature--six were stillborn, eight died shortly after birth, and only five survived infancy. All survivors required tracheostomy to maintain an airway. It is difficult to intubate the trachea of these children and early airway management planning is important. We report a neonate who presented with a prenatal ultrasound diagnosis of severe micrognathia, polyhydramnios and a family history of severe micrognathia. Airway management was achieved with fiberoptic intubation through a laryngeal mask airway (LMA) during an ex utero intrapartum treatment procedure. Fiberoptic intubation was hampered by copious amounts of amniotic fluid. This child and her sibling are the first two siblings with isolated dysgnathia complex to have survived infancy and provide further support for a genetic basis to this condition.     

Fetal heart rate monitoring during fetoscopic repair of open spinal neural tube defects: a single-centre observational cohort study

BackgroundDuring fetal surgery, the haemodynamic stability of the fetus depends on the haemodynamic stability of the mother. The primary objective of this study was to assess changes in fetal heart rate (FHR) throughout the different stages of surgery. The secondary objective was to assess potential changes in maternal physiological parameters and their association with FHR.MethodsThis was a single-center observational cohort study conducted between 2015 and 2019 in 26 women undergoing intra-uterine fetoscopic repair of open spina bifida. The primary outcome was FHR. Maternal physiologic parameters were measured at the beginning, during and after surgery. The linear mixed-effects model fitted by maximum likelihood was used to assess changes in each variable at specific times throughout the surgery, and the repeated measures correlation coefficient was used to study the association between FHR and maternal physiological parameters.ResultsOne (3.8%) case of fetal bradycardia (FHR <110 beats per minute) required the administration of intramuscular atropine. No other significant FHR changes were observed during surgery. Maternal oesophageal temperature (P <0.001), lactate levels (P=0.002), and mean arterial pressure (P=0.016) changed significantly during surgery, although none of these changes was clinically relevant. The FHR showed a significant association with maternal carbon dioxide tension (r=0.285, 95% CI 0.001 to 0.526) and maternal heart rate (r=0.302, 95% CI 0.025 to 0.535).ConclusionThe FHR remained stable during intra-uterine fetoscopic repair of open spina bifida. Maternal carbon dioxide tension and heart rate may have a mild influence on FHR.     

Neonatal outcomes following phenylephrine or norepinephrine for treatment of spinal anaesthesia-induced hypotension at emergency caesarean section in women with fetal compromise: a randomised controlled study

BackgroundNorepinephrine is as effective as phenylephrine for management of spinal anaesthesia-induced hypotension. Most of the studies comparing these vasopressors have been conducted in healthy pregnant women undergoing elective caesarean section. In the current study, we tested the null hypothesis that there is no difference in neonatal outcome when phenylephrine or norepinephrine is used to treat spinal anaesthesia-induced hypotension in women undergoing emergency caesarean section for fetal compromise.MethodsPatients undergoing caesarean section for fetal compromise who developed spinal anaesthesia-induced hypotension were randomised to receive phenylephrine 100 μg or norepinephrine 8 μg for treatment of each hypotensive episode, defined as systolic blood pressure <100 mmHg. Umbilical cord arterial and venous blood samples were obtained for blood gas analysis. The primary outcome measure was umbilical artery pH.ResultsOne hundred patients (50 in each group) were studied. There was no significant difference in umbilical artery pH between the two groups (mean difference 0.001; 95% CI −0.032 to 0.034). The number of hypotensive episodes, vasopressor boluses required, the incidence of bradycardia, heart rate and blood pressure trends following vasopressor administration, and the incidence of nausea/vomiting were not significantly different between groups.ConclusionPhenylephrine 100 μg and norepinephrine 8 μg were not significantly different in terms of neonatal outcome when administered as intravenous boluses for treatment of spinal anaesthesia-induced hypotension in parturients undergoing emergency caesarean sections for fetal compromise.