Anesthesia for Fetal Surgery and Other Fetal Therapies

Anemia and Intrauterine Transfusion

The incidence of fetal anemia secondary to rhesus D (RhD) sensitization has decreased since the introduction of RhD immunoglobulin prophylaxis in the late 1960s, to rates of approximately 1 in 1000 pregnancies. However, other red blood cell (RBC) antigens, parvovirus B19 infection, maternal-fetal hemorrhage, and homozygous thalassemia also cause fetal anemia and combine to reach a rate of approximately 6 cases in 1000 live births. Although spectral analysis examining bilirubin levels in serial amniotic fluid samples was originally used to detect fetal anemia and determine the timing of therapy, most treatment centers currently rely on noninvasive Doppler studies of the middle cerebral artery (MCA). An increased peak MCA blood flow velocity more than 1.5 multiples of the median is an accurate threshold in detecting moderate-to-severe fetal anemia requiring intervention. The value of this peak velocity threshold may be increased with each serial transfusion treatment to decrease the false positive rate. Fetal blood sampling from the umbilical vein just before starting the intrauterine transfusion (IUT) is the gold standard for determining the degree of fetal anemia. IUT is not used before 18 weeks’ GA because umbilical vein access is not reliable. For cases requiring earlier intervention, fetal intraperitoneal transfusion of red cells may initially be the intervention of choice.

IUTs are typically performed using local anesthesia and require minimal maternal sedation and analgesia. However, the anesthesiologist should be prepared for an emergent cesarean delivery at any time during the procedure if the fetus is at a viable GA. Using ultrasound image guidance, a 20- or 22-gauge needle is used to access the umbilical vein. The access point is typically near the placental cord insertion to provide stability ( Fig. 63.1 ). Puncture of an umbilical artery rather than the umbilical vein is associated with prolonged bleeding and fetal bradycardia secondary to spasm. Occasionally a free loop of the umbilical cord or intrahepatic portion of the umbilical vein may be used. The umbilical cord has no known pain receptors, but needle access of the intrahepatic portion of the umbilical vein stimulates pain receptors with passage of the needle into the fetus. Fentanyl attenuates the fetal stress response from intrahepatic fetal needle placement. In one study, fetal stress hormone changes with IUT were unrelated to site of needle placement; however, these results are difficult to interpret because hormone levels may be affected by changes due to the underlying fetal anemia and hemodynamic alterations associated with intravascular volume expansion. Given this uncertainty, fentanyl (10-20 μg/kg) is administered intramuscularly to the fetus before use of an intrahepatic approach. There is some evidence to suggest that fetal anesthesia does not alter MCA peak systolic velocity flow patterns following transfusion.

An intramuscular muscle relaxant (e.g., rocuronium 2.5 mg/kg) can be administered to the fetus to decrease the likelihood of fetal movement that could dislodge the needle or sheer the umbilical vein. If a muscle relaxant is administered directly into the umbilical vein the dose of muscle relaxant can be reduced (e.g., rocuronium 1.0 mg/kg). The volume of type O, rhesus (Rh)-negative, irradiated, viral screened, packed RBCs transfused is estimated from the GA, estimated fetal weight, donor unit hemoglobin (Hb), and pretransfusion Hb. The rate of transfusion is typically 5 to 10 mL/min with a target hematocrit of 45% to 55%. Steady intravascular location of the needle tip can be assessed with Doppler imaging throughout the transfusion injection. Periodic sampling is used to guide the final transfusion volume. After IUT therapy, fetal Hb levels decrease approximately 0.3 g/dL/day and multiple repeat IUTs are typically required at 1- to 3-week intervals, depending on the rate of Hb decline.

Perinatal fetal loss rate is approximately 2% per IUT, and transient fetal bradycardia (8%) is a common complication. Other complications including emergency cesarean delivery, intrauterine infection, preterm PROM, and preterm delivery occur in approximately 3% of IUT procedures. Although survival rates are significantly less for hydropic fetuses, recent published overall survival rates with IUT typically exceed 95%. A long-term outcome study of 291 children (median age of 8.2 years with a range of 2-17 years of age) who underwent IUT during gestation for hemolytic disease found a 4.8% rate of neurodevelopmental impairment, including cerebral palsy (2.1%), severe developmental delay (3.1%), and bilateral deafness (1.0%). Severe fetal hydrops was independently associated with neurodevelopmental impairment.

Congenital Heart Defects

Congenital heart anomalies occur with a frequency of approximately 1/100 live births (see also Chapter 78 ). Ventricular septal defects are the most common cardiac anomaly. The majority of cardiac heart defects are not amenable to fetal intervention. Ultrasound imaging allows diagnosis of cardiac defects as early as 12 to 16 weeks gestation, but is generally performed at 18 to 22 weeks gestation, when obstetric ultrasound assessments are used to screen for other fetal abnormalities.

The majority of fetal surgical cardiac interventions focus on opening a stenotic valve or enlarging a restricted opening. These include (1) aortic balloon valvuloplasty for treatment of critical aortic stenosis and evolving hypoplastic left heart syndrome (HLHS), (2) atrial septostomy for highly restrictive or intact atrial septum seen in HLHS, (3) pulmonic valvuloplasty for pulmonary atresia or intact ventricular septum and hypoplastic right ventricles, and (4) pericardiocentesis to treat congenital cardiac tumors or aneurysms. In utero intervention attempts to halt or reverse the morbid effects of the cardiac lesion before irreversible consequences occur. Early childhood mortality from severe cardiac defects, such as HLHS, remains in the range of 25% to 35%. Survivors have significant associated abnormalities in neurologic development.

The most commonly performed procedure is an aortic valvuloplasty for aortic stenosis with evolving HLHS. Significant aortic stenosis maintains fetal circulation primarily through the low-resistance foramen ovale and diminishes left ventricular development. Selection guidelines for fetal aortic valvuloplasty focus on the presence of significant aortic stenosis, evolving HLHS, and the potential for a technically successful procedure and biventricular postnatal outcome. For this procedure, the fetus is ideally positioned with the left chest anterior, and ultrasound is used to guide the percutaneous passage of an 18- or 19-gauge needle cannula through the uterus, through the fetal chest, and into the apex of the left ventricle ( Fig. 63.2 A ). Maternal local anesthesia infiltration or neuraxial block is typically used for these procedures, and fetal resuscitation drugs must be readily available. In some cases, general anesthesia may be preferred for uterine relaxation to facilitate an external version to change fetal position and improve cannula trajectory. Before cannula insertion, intramuscular fentanyl and a paralytic agent are administered to the fetus with ultrasound guidance, as detailed in the section on “Fetal Anesthesia, Analgesia, and Pain Perception.”

The cannula tip is ideally positioned in the left ventricle, directly in front of the opening of the stenotic aortic valve and aligned with the left ventricular outflow tract. A coronary balloon catheter with guidewire is passed through the cannula into the stenotic valve and positioned in the aortic annulus, where it is inflated and deflated multiple times (see Fig. 63.2 B ). In certain cases, a small laparotomy is used to facilitate improved cannula alignment with the cardiac lesion. Technical success for fetal aortic valvuloplasty is approximately 75% using an angioplasty balloon over a guidewire. [CR] Technical success creates improved left ventricular function, improved aortic and mitral valve development, and birth of a live neonate in 90% of interventions. Fetal complication rates from centers in Linz, Austria ( n = 24) and Boston ( n = 70) for fetal aortic valvuloplasty include: fetal bradycardia (17% and 38%, respectively), pericardial effusion (13% and 14%, respectively), ventricular thrombosis (21% and 15%, respectively), and fetal death (13% and 8%, respectively). A recent systematic review noted complication rates following fetal aortic valvuloplasty of preterm delivery (16%), neonatal death (16%), bradycardia (52%), and hemopericardium (20%). Approximately 40% of technically successful cases result in aortic regurgitation and minimal subsequent left ventricular growth. Biventricular circulation is present at birth in approximately half of the successful cases.

In addition to treatment of aortic stenosis, other cardiac anomalies have been treated in utero. Similar surgical techniques are used for atrial septoplasty and pulmonary valvuloplasty. Outcomes from a small series of fetal atrial septostomies are promising; however, the defect created by the balloon dilation tends to close over time unless a stent is placed (which can be difficult and deployment has been successful in only 44%-62% of the time in a small case series). Pulmonary valvuloplasty for pulmonary atresia and prevention of hypoplastic right ventricle was technically successful in 7 of 11 procedures, but long-term outcome data are unavailable. In utero placement of cardiac pacing has been investigated to treat fetal cardiac arrhythmias unresponsive to conventional management with transplacentally administered antiarrhythmic drugs. Unfortunately, these initial attempts have been frequently unsuccessful.

Obstructive Uropathy

Fetal LUTO affects 2 in 10,000 live births. These obstructions can be bilateral or unilateral and occur at the ureteropelvic junction, at the ureterovesical junction, or at the level of the urethra. If the obstruction is urethral or bilateral, significant developmental consequences occur ( Box 63.1 ). Rates of perinatal mortality in these cases are as high as 90%, and survivors have more than 50% renal impairment.

Posterior urethral valves are the most common cause of congenital bilateral hydronephrosis in male fetuses. Urethral obstruction is the most common cause in females, with other possible causes including ectopic ureter, ureterocele, megacystis megaureter, multicystic kidney, or other complex pathologic processes. Ultrasound investigations of oligohydramnios resulting from decreased fetal urine output easily detect these uropathies with high sensitivity and specificity. Fetal MRI should be considered in cases of severe oligohydramnios as an additional imaging technique to determine the presence of associated fetal anomalies. Grading systems based on ultrasound imaging of renal diameter to determine the severity of hydronephrosis and assessment of urinary tract dilation are used to determine risk stratification and treatment options. Recently, a classification system for LUTO has been proposed that is based on amniotic fluid index, renal imaging, and fetal urine chemistry. The associated morbidity predicted for each type of uropathy depends on obstruction location, duration, gender, and GA at onset. Preterm delivery allows neonatal urinary tract decompression, but morbidity from pulmonary immaturity prevents early intervention and limits the efficacy of this approach.

Poor prognosis is associated with earlier presentation during gestation, more severe oligohydramnios, associated structural abnormalities, and increased concentrations of fetal urine electrolytes, osmolality, protein, and β ₂ -microglobulin. Each case should be thoroughly investigated to determine whether other anomalies are present and if the fetus is a suitable candidate for intervention. If LUTO is corrected postnatally, 25% to 30% of surviving neonates will require dialysis by age 5.

Placement of an in utero fetal vesicoamniotic shunting (VAS) for in utero treatment of LUTO allows decompression of the fetal bladder and urinary tract into the amniotic cavity. VAS prevents urine accumulation, allows normal bladder emptying and development, improves dysplastic renal histologic conditions, increases amniotic fluid volume, improves lung development, and prevents bladder wall fibrosis in animal models. Determination of which human fetuses would benefit from in utero treatment of LUTO remains uncertain. Human VAS placement started in the 1980s in an effort to improve renal development and reduce the pulmonary hypoplasia associated with oligohydramnios. These valveless, double-coiled shunts are inserted percutaneously with ultrasonographic guidance and local anesthesia. One coil remains in the urinary bladder and the other in the amniotic cavity. Prior infusion of fluid into the amniotic cavity can aid in proper shunt placement. Complications associated with these shunts include difficult placement, subsequent occlusion, and position migration (malfunction occurs in up to 60% of cases). Fetal and maternal complications include fetal trauma, iatrogenic abdominal wall injury, gastroschisis, amnioperitoneal leaking, preterm PROM, preterm labor and delivery, and infection. Neonatal survival rates after fetal VAS vary in the literature from 40% to 90%, with approximately 50% of survivors having normal renal function. A metaanalysis of LUTO treatment studies through 2015 noted a perinatal survival advantage with in utero VAS placement compared to standard care (57% vs. 39%), but ultimately there was no difference in renal function or 2-year survival. A multicenter, randomized controlled trial (the Percutaneous Shunting in Lower Urinary Tract Obstruction [PLUTO] trial) compared the perinatal mortality and renal function of fetuses with LUTO treated by either VAS or conservative noninterventional care. The trial was unable to recruit sufficient cases, with only 31 out of 150 desired patients recruited over a 4-year period. Analysis of this smaller enrollment noted a mortality benefit in the fetal treatment group at 28 days, 1 year, and 2 years of age; however substantial morbidity occurred in both groups, leading to only two children with normal renal function at 2 years of age.

Fetal cystoscopy is a recent intervention that allows prenatal visualization of the fetal urethra and ablation of the urethral obstruction. Cystoscopy facilitates diagnosis between LUTO resulting from urethral atresia and posterior urethral valves. This is an important distinction, as urethral atresia is nearly universally lethal and does not improve with VAS placement, while posterior urethral valves are amenable to fetal intervention. Ablation of posterior urethral valves may increase survival compared with expectant management. A case series and retrospective case control study demonstrated that fetoscopic laser ablation for posterior urethral valves can achieve bladder decompression and amniotic fluid normalization. In addition, fetal cystoscopy may improve 6-month survival in severe LUTO compared to no fetal intervention and result in improved renal function at birth when compared to treatment with VAS. Future prospective trials are necessary to validate these initial retrospective results.

Selective fetal intervention with shunting or cystoscopy for LUTO restores amniotic fluid volume, prevents pulmonary hypoplasia, and improves perinatal mortality. However, the effects on medium-term and long-term renal function, neurologic function, bladder function, and other morbidities remain unclear and additional clinical research is needed.