New Trends in Fetal Anesthesia

Fetal anesthesia teams must understand the pathophysiology and rationale for the treatment of each disease process. Treatment can range from minimally invasive procedures to maternal laparotomy, hysterotomy, and major fetal surgery. Timing may be in early, mid-, or late gestation. Techniques continue to be refined, and the anesthetic plans must evolve to meet the needs of the procedures. Anesthetic plans range from moderate sedation to general anesthesia that includes monitoring of 2 patients simultaneously, fluid restriction, invasive blood pressure monitoring, vasopressor administration, and advanced medication choices to optimize fetal cardiac function.

Key points

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Minimally invasive procedures typically are performed with moderate sedation, but neuraxial or general anesthetics may be used. These procedures typically are done for complicated multiple gestations but also may be done to treat cardiac abnormalities, cystic lung lesions, diaphragmatic hernia, lower urinary tract obstruction, and sacrococcygeal teratoma.
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Open mid-gestation fetal surgery is performed most commonly to repair fetal myelomeningocele. These cases typically require maternal general anesthesia with additional measures to optimize fetal cardiac function, uterine relaxation, and maternal and fetal perfusion. The fetus is returned to the uterus to continue growth and development.
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Ex utero intrapartum therapy is performed for fetuses that need help transitioning to extrauterine life. The anesthetic is similar to that for mid-gestation surgery, but the uterine relaxation must be reversed promptly after the baby is delivered. A second team must be prepared to receive the newborn after the procedure is completed.

Introduction

Fetal therapy is a new field that is beginning to mature as more fetal treatment centers are being established and collaborative efforts are undertaken to improve the care of the mother and fetus.

Anesthetic management should be grounded in an understanding of the pathophysiology of the underlying fetal anomaly, the rationale, and the technical details of the fetal intervention. Practical considerations also include the preferences and philosophies of the practitioners and the infrastructure, staffing models, and characteristics of the patient population.

A discussion of the physiology of pregnancy, the fetus, and the placenta can be found in other resources. What follows is an overview of the diseases that are diagnosed more commonly and treated in the prenatal or immediate postnatal periods. The rationale and approach to treatment are presented. A common endpoint of many fetal disease processes is hydrops fetalis, which often is the symptom that prompts a fetal intervention. If the fetus develops hydrops, the mother also is at risk of developing pulmonary edema from maternal mirror syndrome. Supportive therapy for the mother and treatment of the fetal disease process will treat the maternal mirror syndrome. Detailed discussion of the outcomes of the various inventions is beyond the scope of this review. The anesthetic management is broken down into minimally invasive, open mid-gestation, and ex utero intrapartum therapy (EXIT) procedures.

Diseases and treatments

Complicated Multiple Gestation

Twin-twin transfusion syndrome (TTTS) is a complication of monochorionic twin pregnancy, where one twin (the recipient) becomes hyperdynamic and hypervolemic. Polyuria, polyhydramnios, and cardiac changes, such as ventricular hypertrophy and dilation, may develop. The other twin (the donor) becomes hypovolemic, with ensuing oliguria and oligohydramnios. Both twins are at risk for death, preterm delivery, and periventricular leukomalacia. A similar situation may develop where there is a discrepancy in the hemoglobin concentration between the twins in the absence of a discrepancy in amniotic fluid volume. This condition is known as twin anemia-polycythemia sequence. In some cases, one or both twins may have other concomitant congenital abnormalities. In some cases, twin reversed arterial perfusion (TRAP) sequence may develop. One twin may not develop a heart, and the normal pump twin provides perfusion to the acardiac twin.

The treatment of complicated multiple gestations depends on the therapeutic goals. If the goal is for both twins to survive, fetoscopic ablation of the problematic vascular anastomoses is undertaken with laser energy, which should result in more balanced blood flow to both twins. In some cases, the family and surgical team may opt to maximize the chances for only one twin’s survival. ^, In these cases, radiofrequency ablation (RFA) of the umbilical cord of the other twin is performed. If the twins happen to be both monochorionic and monoamniotic, the umbilical cord that has been treated with RFA also must be divided to prevent a cord accident from the entanglement of the twins and their umbilical vessels.

Airway Obstruction

Fetal airway obstruction can be divided into extrinsic and intrinsic causes. A majority of fetuses with extrinsic airway obstruction due to a mass or micrognathia do not require therapy in the middle of gestation because they are on placental circulatory support. The problems arise at birth, because the airway obstruction impedes the newborn’s first breath. Intrinsic obstruction from a laryngeal web or atresia may require therapy in the middle of gestation if the airway obstruction is so severe that lung fluid cannot escape to the amniotic fluid. If the trapped lung fluid causes overdistension of the fetal lungs, the fetal heart is compressed and hydrops fetalis may develop. Mid-gestation therapy only attenuates the causes of the hydrops, and further measures still are required to ensure a secure airway at birth.

The treatment of fetal airway obstruction at birth requires risk stratification. ^, If there is little to no chance a secure airway can be established expeditiously immediately after birth, EXIT delivery is undertaken, which involves actions to secure the airway before the umbilical cord is clamped. Because the umbilical cord is patent, the fetal airway may be secured in a controlled manner over the course of an hour or more, as long as the uteroplacental interface is intact. The airway may be secured by direct laryngoscopy, rigid bronchoscopy, or tracheostomy, and mass debulking or resection also may occur.

If there is a reasonable chance the newborn airway can be secured after birth, or if the mother is not a candidate for an EXIT delivery, arrangements are made to have a second full team, including nursing, neonatal, anesthesia, and surgical providers present for the birth of the child. These teams assess the neonate at birth and act according to clinical needs. This may involve no intervention, application of continuous positive airway pressure, intubation with direct or video laryngoscopy, fiberoptic or rigid bronchoscopy, or tracheostomy. Appropriate nomenclature, communication, booking of cases, and organizing of teams can be unwieldy in these situations, so the phrase, Procedure REquiring Second Team in the Operating room (PRESTO), was developed to facilitate communication between all the involved teams. At the Children’s Hospital of Philadelphia, this type of case is denoted by PRESTO for airway.

Treatment of intrinsic airway obstruction in the middle of gestation is undertaken less commonly. This may involve using a fetoscope and laser to create a defect in a tracheal web. As the lung fluid escapes through the new defect, the lungs and heart decompress. Even if the airway decompression is successful, and the hydrops resolves, the fetus still may require an EXIT delivery. The defect created by the laser only allows decompression of the airway and lungs, but the defect is likely not large enough to allow adequate ventilation with a natural airway or easy passage of an endotracheal tube.

Lung Masses

Lung masses, such as congenital pulmonary airway malformation, bronchopulmonary sequestration, and hybrid lesions, threaten the fetus in a variety of ways. Mass effect causes mediastinal shift and cardiac tamponade physiology, which may cause nonimmune hydrops. A large lesion also prevents the growth of normal lung tissue.

Treatment of lung lesions varies depending on the symptomatology and characteristics of the lesion. In many cases, no fetal intervention is required, the pregnancy may be carried to term, and the child can be scheduled for an elective lobectomy. If the lung lesion is large, with evidence of mediastinal shift, radiographic evidence of significant hypoplasia, or other concerning factors, the surgical and obstetric teams may consider a cesarean delivery, with a PRESTO thoracotomy or an EXIT procedure with a fetal thoracotomy. Even larger lesions may cause hydrops in the middle of gestation and prompt the surgical teams to intervene earlier. If the lesion has macrocysts, serial aspirations or continuous drainage with a shunt alleviates cardiac compression. If the lesion is solid or otherwise not amenable to minimally invasive approaches to decompression, open fetal surgery with fetal thoracotomy and resection of the lesion is performed. The fetus then is placed back in the uterus to continue gestation.

Heart Defects

Catheter-based cardiac interventions are performed for various indications. The more common indications include fetuses with (1) severe aortic stenosis and evolving hypoplastic left heart syndrome (HLHS); (2) pulmonary valve atresia, intact atrial septum, and evolving hypoplastic right heart syndrome; or (3) HLHS with an intact or highly restrictive atrial septum. In the first 2 cases, the catheter-based intervention consists of an aortic or pulmonary balloon valvuloplasty, with the hope of improving blood flow through the hypoplastic ventricle and promoting the development of a biventricular circulation. In the third case, the treatment consists of a fetal atrial septoplasty, with either a balloon or stent. The goal is simply to improve survival at birth because a newborn with HLHS and an intact atrial septum does not have any pathway for blood to travel from the lungs to the systemic circulation. The cardiac interventions often are carried out percutaneously by placing a catheter system across the maternal abdominal wall, uterus, and fetal chest wall into the heart. In some cases, the surgical and cardiac team may opt to perform a laparotomy to access the uterus and fetal heart more easily.

Open fetal surgery to resect fetal pericardial teratomas with mass effect on the heart has been performed. This therapy involves a maternal laparotomy and hysterotomy, followed by a fetal sternotomy and resection of the teratoma. After fetal chest closure, the fetus is returned to the uterus.

Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) has been a target of fetal therapy for decades. Various attempts at primary fetal repair or tracheal occlusion to allow lung growth were studied, but these strategies required at least 1 if not 2 major surgical procedures on the mother, and neonatal outcomes after these fetal interventions were equivalent to standard postnatal CDH repair. Open fetal therapy for CDH, therefore, currently is not performed.

Newer minimally invasive, fetoscopic endoluminal tracheal occlusion involves placing a balloon in the fetal trachea between 27 weeks’ and 31 weeks’ gestation. These balloons are removed fetoscopically after 4 weeks to 6 weeks. The balloon promotes lung growth while in place, and, after the balloon is removed, the mother may deliver vaginally. European results have been promising, but these studies were not randomized. The Tracheal Occlusion To Accelerate Lung Growth trial is under way at multiple institutions around the world. ^,

Myelomeningocele

Prenatal repair of myelomeningocele (MMC) has been shown to improve motor and sensory function and reduces the need for shunting of cerebrospinal fluid after birth. ^, As with any open mid-gestation fetal surgery, the treatment involves performing a maternal laparotomy and hysterotomy to access the fetal MMC. The MMC is repaired with various surgical techniques, and the fetus is replaced in the uterus.

In efforts to further decrease maternal morbidity from major surgery and even allow vaginal delivery, some fetal surgical teams are performing fetoscopic MMC repair. This fetoscopic approach still requires a maternal laparotomy, but the uterus is not opened. The risk of preterm labor is attenuated, and vaginal delivery is an option if no other maternal contraindications exist. These advantages, however, come with the cost of longer surgical time and less clear neonatal outcomes. The specific surgical techniques have varied over time and between institutions. The techniques have ranged from single-layer to 3-layer closures of the MMC, with occasional use of patches.

Lower Urinary Tract Obstruction

Lower urinary tract obstruction (LUTO) leads to renal damage and pulmonary hypoplasia. Posterior urethral valves are the most common cause of LUTO. Decompression of the urinary tract is the goal of the prenatal intervention. If fetal imaging suggests a prenatal intervention may be helpful, serial samples of fetal urine are collected and analyzed to guide decision making for invasive fetal intervention. Therapeutic decisions are challenging in cases of LUTO, because the prognosis must be grim enough to warrant an intervention, although not so grim that the renal system is not salvageable. Interventions have included open fetal surgery, but most interventions are minimally invasive, such as serial vesicocentesis, placement of a vesicoamniotic shunt, and fetal cystoscopic procedures.

Sacrococcygeal Teratoma

A large sacrococcygeal teratoma (SCT) imposes a great metabolic burden on the fetus that can cause high-output heart failure. Although the fetal decompensation may be rapid, heart failure occurs more typically in a time frame that allows monitoring of the heart, tumor, and fetal growth. The treatment of fetal SCT is individualized and depends on the fetal physiology, tumor morphology, and expertise of the fetal treatment center.

Interventions for prenatally diagnosed SCT include minimally invasive tumor ablation, open fetal debulking, EXIT procedure, and early delivery with debulking or complete resection immediately at birth.

Types of fetal interventions

Fetal interventions can be divided into minimally invasive, open mid-gestation, and EXIT procedures. ^, Minimally invasive fetal interventions are the most common and typically are performed in early gestation or mid-gestation. Using ultrasound guidance, needles or trocars are inserted into the amniotic cavity, without the need for a hysterotomy. ^, During needle-based procedures, needles are inserted percutaneously under ultrasound guidance. During fetoscopic interventions, a 2.3-mm to 4.0-mm (7F to 12F) trocar that accommodates a 1.2-mm to 3-mm endoscope is placed percutaneously into the amniotic cavity with ultrasound guidance. Occasionally, a laparotomy may be necessary to exteriorize the uterus for complex fetoscopic repairs or when an anterior placenta precludes a percutaneous approach. ^, Common indications for minimally invasive fetal interventions and their pathophysiology are listed in Table 1 .

Table 1

Common indications for minimally invasive interventions and open fetal surgery

Fetal Malformation	Pathophysiology	Fetal Intervention
Fetal anemia	Causes include Rh isoimmunization, parvovirus B19 infection, twin anemia-polycythemia sequence, etc; results in fetal heart failure and hydrops	Intrauterine blood transfusion
TTTS	Monochorionic-diamniotic twin pregnancy with unbalanced flow across placental intertwin vascular anastomoses. Donor twin develops oligohydramnios and growth restriction. Recipient twin develops polyhydramnios, cardiomyopathy, and hydrops. High risk of fetal demise and adverse neurologic outcomes	Serial amnioreduction
		Selective fetoscopic laser photocoagulation
		Selective fetal reduction via RFA
TRAP sequence	Monochorionic twin pregnancy with 1 acardiac twin. Normal (pump) twin provides retrograde perfusion to the acardiac twin, resulting in congestive heart failure, polyhydramnios, and preterm delivery	RFA of acardiac twin
LUTO	Dilated thick-walled bladder, renal dysplasia, and severe oligohydramnios; neonatal renal and respiratory failure	Vesicoamniotic shunt placement
LUTO		Fetal cystoscopy and ablation of posterior urethral valves
Congenital cystic lung lesions	Congenital pulmonary airway malformation or pleural effusion causing pulmonary hypoplasia, mediastinal shift, hydrops, and polyhydramnios	Serial thoracocentesis
		Thoracoamniotic shunt placement
		Open fetal lobectomy
CDH	Herniated abdominal viscera and lung compression results in pulmonary hypoplasia and pulmonary hypertension	FETO, followed by the reversal of tracheal occlusion
Amniotic band syndrome	Constrictive amniotic bands with entanglement of fetal parts, leading to limb amputation, syndactyly, craniofacial or body wall defects	Fetoscopic laser release of amniotic bands
Aortic stenosis with evolving HLHS	Progressive left ventricular dysfunction and arrested growth of left-sided heart structures	Fetal aortic valvuloplasty with balloon dilation of aortic valve
HLHS with intact atrial septum	Absent or restricted left-to-right flow across foramen ovale leads to pulmonary venous hypertension; if present at birth, results in cyanosis, acidosis, and death	Fetal atrial septostomy
MMC	Damage to exposed spinal cord and Chiari II malformation leads to lower extremity paralysis and obstructive hydrocephalus	Open fetal MMC repair Fetoscopic MMC repair
SCT	Arteriovenous shunting, high-output cardiac failure, hydrops, and placentomegaly	Fetoscopic laser ablation Laser RFA Open fetal surgery