Fetal interventions range from minimally invasive fetoscopic surgery to mid-gestation open surgery, to ex-utero intrapartum treatment (EXIT) procedure prior to delivery. Anesthetic management depends on the type of fetal intervention and patient characteristics. Evidence-based practice in fetal anesthesia is hindered by the small numbers of cases and the heterogeneity of anesthetic management across institutions, with most research consisting of single center observational studies.
A recent review article discussed the management of EXIT procedure and some fetal procedures, including fetal cardiac interventions [1▪▪]. We will address the anesthetic management for other noncardiac fetal procedures, including the management of lower urinary tract obstruction, congenital diaphragmatic hernia (CDH), myelomeningocele, sacrococcygeal teratoma, prenatally anticipated difficult airway and congenital lung lesions.
LOWER URINARY TRACT OBSTRUCTION
Lower urinary tract obstruction is a complex fetal genitourinary disorder involving partial or complete obstruction of fetal bladder outflow that can cause upstream in utero urinary congestion and impaired bladder and renal function . Lower urinary tract obstruction can present with a variety of features ranging from isolated bladder dilatation with normal amniotic fluid levels to anhydramnios and severe urinary tract dilatation . Fetal ultrasound can be used to determine disease severity and guide fetal therapy, which may consist of ultrasound monitoring, vesicoamniotic shunt placement, fetal cystoscopy or amnioinfusion [2,3▪]. Although fetuses treated with vesicoamniotic shunts have improved perinatal survival when compared to conservative management, rates of renal morbidity remain high . A recent meta-analysis consisting of mainly nonrandomized studies found significant variation in fetal selection criteria for conservative management versus intervention;  additionally, follow up of longer term outcomes, such as need for renal replacement therapy, is needed.
For minimally invasive prenatal procedures, mothers may receive epidurals [3▪] or monitored anesthesia care using intravenous medications and local anesthesia for trocar placement [6▪]. Fetal anesthesia may be achieved by an intramuscular injection of a narcotic and nondepolarizing paralytic can be administered directly to the fetus through the trocar access to the uterus, and/or placental transfer of maternal intravenous sedation medications.
CONGENITAL DIAPHRAGMATIC HERNIA
CDH can be diagnosed in the prenatal period, and morbidity and mortality arise from pulmonary hypoplasia and pulmonary hypertension. The logic behind prenatal treatment of CDH is to allow the fetal lung more time to develop before birth. The search for effective fetal treatment of CDH is ongoing. Early fetal therapies included primary repair of the diaphragmatic defect or occlusion of the fetal trachea via hysterotomy to promote lung growth distal to the occlusion. Both strategies required at least one if not two major maternal surgical procedures, and fetal outcomes were equivalent to postnatal medical management and surgical repair [7,8▪].
A recently developed minimally invasive approach involves mid-gestation occlusion of the fetal trachea with a balloon. The balloon is inserted between 27 and 31 weeks gestation with a minimally invasive fetoscopy approach and is ideally removed at 34 weeks gestation. This approach reduces maternal exposure to surgical morbidity and in the best-case scenario allows for vaginal delivery at term. European results have been promising, but these studies were not randomized [9,10]. The Tracheal Occlusion to Accelerate Lung growth Trial is a multicenter, international effort comparing prenatal therapy to ‘expectant’ management .
The anesthetic and tocolytic management of fetoscopic balloon placement should be guided by institutional standards, which range from maternal sedation supplemented with local anesthetic to neuraxial or general anesthesia, depending on maternal anesthesia risk factors. A recent retrospective review of maternal anesthetic management found no conversions to general anesthesia among the group of tracheal occlusion patients initially selected to receive intravenous sedation . The fetus receives an intramuscular injection of fentanyl and vecuronium before balloon placement. Postoperative tocolytic requirement is extremely rare. Ideally, balloon removal is performed with the same anesthetic technique as for insertion. In the setting of an unplanned delivery, the tracheal balloon must be removed so that the neonate can breathe. Removal may take place during delivery with an EXIT procedure or with a bronchoscope after cesarean delivery. The personnel and equipment to care for these patients during an unplanned delivery must be readily available. These situations require quick decision making, seamless lines of communication and a high-functioning, flexible care team.
In-utero repair of myelomeningocele is performed to attenuate the multiple sources of neurologic injury in this disorder. The initial abnormality of incomplete closure of the neural tube is exacerbated by subsequent spinal cord exposure to amniotic fluid during gestation. A Chiari II malformation may develop in these cases, and hydrocephalus may develop secondary to this malformation. In-utero myelomeningocele closure can, therefore, limit this second cause of neural damage and can also reverse or improve the hindbrain herniation of the Chiari malformation. The Management of Myelomeningocele Study (MOMS) compared open fetal surgery to postnatal repair and found lower rates of ventriculoperitoneal shunt placement (40 versus 82%) and hindbrain herniation (64 versus 96%) in the prenatal surgery group . Motor function and mental developmental scores were improved at 30 months [14▪▪]. There were increased obstetric complications in parturients who underwent open fetal surgery, including chorioamniotic membrane separation, spontaneous membrane rupture, oligohydramnios, pulmonary edema and uterine dehiscence or thinning at the site of open fetal surgery hysterotomy. Infants who underwent fetal surgery had higher rates of premature birth with an average gestational age of 34 weeks and prematurity of less than 30 weeks in 11% . Multiple centers have published their post-MOMS trial data and found similar results with improvements in blood transfusion at delivery, chorionic membrane separation and pulmonary edema [15–18].
The initial anesthetic for fetal myelomeningocele repair was a rapid sequence induction and deep general anesthesia with high-dose volatile anesthetics for uterine relaxation during manipulation. Volatile anesthetics cross the placenta and can cause decreased fetal cardiac function that worsens over time. Some centers use remifentanil, propofol or epidural anesthesia to decrease the volatile anesthetic requirement [19,20,21▪▪]. A retrospective observational study found that giving magnesium sulfate early in open fetal surgery allowed sufficient uterine relaxation with lower volatile concentration .
To further reduce the complication rate of open fetal surgery, some centers are developing fetoscopic repair techniques. Although this approach is promising, direct comparisons between fetoscopic repair and open fetal surgery are limited by the variety of fetoscopic techniques and the resulting small numbers of patients treated with each surgical approach. Fetoscopic repair is performed percutaneously or via laparotomy with exteriorization of the uterus [23–25]. There is heterogeneity in closure technique for the defect and the uterine port sites. A recent meta-analysis compared a total of 257 open fetal surgery patients to 179 patients treated with fetoscopic repair and found no difference in the combined primary outcome of death (6 versus 7%, P = 0.65) or ventriculoperitoneal shunt placement at 12 months (40 versus 42%, P = 0.73). Fetoscopic repairs had higher rates of dehiscence or leakage from the repair site, but there was higher uterine dehiscence after open fetal surgery [26▪▪]. Additional study of long-term neurologic outcomes to establish surgical equivalency of the fetoscopic repair is merited . A recent study reported approximately half of mothers delivered vaginally after fetoscopic repair .
There may be important differences between open fetal surgery and the two types of fetoscopic repairs. Open fetal surgery is shorter, with less time for accumulation of volatile agent in the fetus. The significantly longer duration of fetal exposure to volatile anesthetic in fetoscopic surgery could have neurodevelopmental ramifications [28▪▪]. Conversely, more uterine manipulation in open fetal surgery may require higher doses of volatile agent. A small retrospective study of open fetal surgery compared to fetoscopic repair found higher doses of volatile anesthetics were used in the open fetal surgery group. The period associated with the highest volatile anesthetic level was exteriorization of the uterus for both surgical approaches [21▪▪]. In contrast, a study of the percutaneous fetoscopic approach used less than 1 MAC of desflurane with remifentanil . Although not available in the United States, the tocolytic atosiban is used in multiple centers outside the United States during these procedures.
Sacrococcygeal teratomas (SCTs) are the most common tumor in the newborn, with an incidence of 1 in 35,000–40,000 live births . SCTs are classified as types 1 through 4 based on abdominopelvic extension, and they vary in their composition with cystic and solid components. Fetal MRI is the preferred imaging modality for determining the tumor extent and composition. Tumor volume to fetal weight ratio less than 0.12 is associated with poorer outcomes, whereas noncystic composition is associated with higher transfusion volume [30–32].
SCTs diagnosed before birth have a mortality rate of 30–50% . Fetal ultrasound is used to monitor for rapid tumor growth or bleeding into the tumor, which can lead to high output cardiac failure. Placentomegaly, fetal hydrops and fetal demise are end stages of this process and can lead to maternal mirror syndrome, the term for development of maternal edema and other symptoms associated with fetal hydrops. Intervention is recommended prior to fetal or maternal decompensation, and the risk of preterm delivery is weighed against the maternal risk of fetal surgery. In-utero open fetal surgery was traditionally considered in select fetuses prior to 32 weeks gestation . Recent reports of preemptive cesarean delivery between 27 and 32 weeks with immediate resection in fetuses exhibiting signs of decompensation have shown favorable fetal outcomes with less maternal risk [34▪]. Minimally invasive percutaneous laser ablation or radiofrequency ablation of tumor vasculature has recently been described [35,36]; however, larger studies are needed to determine if these interventions are beneficial.
Anesthesia for in-utero open fetal surgery for tumor debulking with the goal of continuing the pregnancy after the resection is achieved with maternal general anesthesia with volatile anesthetic and intravenous nitroglycerin as needed for uterine relaxation, similar to the anesthetic plan for open fetal myelomeningocele repair. The fetus is partially exposed and intravenous access is obtained. Pulse oximetry and echocardiography are used to monitor fetal heart rate and cardiac function, respectively. Most importantly, the team should be prepared to treat massive fetal blood loss and coagulopathy .
ANTICIPATED DIFFICULT AIRWAY
Neonatal high airway obstruction can be life-threatening after delivery. There are multiple possible causes of airway obstruction. Congenital masses, such as teratomas, cystic hygromas, and lymphangiomas and craniofacial syndromes with micrognathia, retrognathia, mandibular hypoplasia and tongue obstruction, are potential causes of extrinsic airway obstruction. Congenital high airway obstruction syndrome because of laryngeal atresia or stenosis causes intrinsic airway obstruction [37,38▪]. Advances in prenatal imaging have enabled earlier identification and monitoring of airway anomalies. The treatment plan depends on the degree of airway obstruction and anticipated difficulty of airway management . Direct measures of airway obstruction include mass size and location and airway patency and deviation. Indirect measures of severe airway obstruction include polyhydramnios, lack of fetal swallowing, absence of stomach fluid and lack of cycling stomach.
The airway may be secured while on placental circulation via EXIT procedure or after separation from the placenta. During EXIT, neonatal gas exchange is maintained by the placenta, whereas the neonate is partially delivered through a hysterotomy. The procedure typically lasts from several minutes to roughly an hour and can be limited by complications, including development of placental abruption. The potential benefit to the fetus must be weighed against the risk to the mother [40,41,42▪▪]. EXIT procedure is generally reserved for fetuses, where ventilation is anticipated to be impossible via bag mask or supraglottic airway. Congenital high airway obstruction syndrome and large, obstructive airway masses fall into this category. Anesthetic considerations for EXIT procedure are described in a recent review by Weber and Kranke [1▪▪] and others .
Postdelivery airway management is indicated for fetuses in whom ventilation by mask or supraglottic airway is anticipated to be feasible or when the EXIT procedure is contraindicated because of maternal condition or refusal . Craniofacial syndromes and airway masses that are not completely obstructive fall into this category. Anesthetic management will depend on the clinical situation, but a supraglottic airway can often be used prior to securing a definitive airway. Maintaining spontaneous ventilation while providing sedation for flexible or rigid bronchoscopy, or direct or indirect laryngoscopy, will aid in maintaining oxygenation during the procedure. A multidisciplinary team of otolaryngologists, neonatologists, anesthesiologists, respiratory therapists and neonatal ICU nurses should be immediately available to provide airway management after delivery.
FETAL LUNG LESIONS
Improvements in ultrasound and MRI have facilitated prenatal diagnosis and fetal treatment of congenital lung lesions. A comprehensive review of this topic is available [45▪]. Most fetal interventions are performed for patients with cystic pulmonary airway malformations formerly called congenital cystic adenomatoid malformations [45▪], which are characterized as microcystic or macrocystic. Prenatal steroids can significantly shrink microcystic lesions, although not all respond to treatment. Macrocystic lesions expand later in gestation. Lung mass expansion can lead to pulmonary hypoplasia, mediastinal shift with impairment of venous return and fetal hydrops [45▪]. The cystic pulmonary airway malformation volume ratio (CVR) normalizes the lesion size to the fetal head circumference, with a CVR greater than 1.6 predictive of development of fetal hydrops . Other congenital lung lesions include bronchopulmonary sequestrations, hybrid lesions with elements of cystic pulmonary airway malformations and bronchopulmonary sequestrations, congenital lobar emphysema, bronchogenic cysts and bronchial atresia. Although cystic pulmonary airway malformations communicate with the airway, bronchopulmonary sequestrations do not. Bronchopulmonary sequestrations have systemic vascular supply and can be intralobar or extralobar. Like macrocystic cystic pulmonary airway malformations, intralobar bronchopulmonary sequestrations and congenital lobar emphysema can become enlarged. Extralobar bronchopulmonary sequestrations containing abnormal lymphatic tissue can secrete fluid that may cause a hydrothorax . Despite prenatal imaging advances, prenatal diagnosis of the lung lesion type can be inaccurate.
Anesthetic management is tailored to the required fetal intervention, which can include thoracentesis, thoracoamniotic shunt placement, mid-gestation open fetal surgical resection or an EXIT procedure with lesion resection prior to separation from the mother [45▪]. An alternative to EXIT for infants who are likely to have postdelivery respiratory distress is scheduled cesarean delivery with a second team and operating room set up to perform the postnatal lung resection immediately [45▪,46]. For macrocystic cystic pulmonary airway malformations, bronchopulmonary sequestrations with fluid secretion and congenital lobar emphysema, thoracoamniotic shunts can be placed percutaneously using ultrasound guidance. Anesthesia often consists of intravenous sedation supplemented with local anesthetic infiltration, similar to other minimally invasive fetal interventions. Mid-gestation open fetal resection management is similar to the anesthetic regimen for open fetal myelomeningocele repair as uterine relaxation and postoperative pain control are both needed. However, the fetus is partially delivered, monitored with pulse oximetry and intravenous access is established. The anesthetic for the EXIT procedure has been recently described [1▪▪].
Advances in fetal imaging studies have enhanced the diagnosis and treatment for rare congenital anomalies. Maternal anesthetic management for these interventions ranges from intravenous sedation to general anesthesia. There is institutional variability in surgical and anesthetic management, particularly for myelomeningocele repair. More multiinstitutional collaboration and higher quality of evidence is needed to guide the optimization of management of these challenging cases.
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Conflicts of interest
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REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
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