Anaesthesia for Fetal Surgeries and Therapies

Dr. Amrusha Choukasey
Assistant Professor,
Department of Anaesthesiology,
GMC, Nagpur

Only recently have medical professionals focused on the human fetus as a patient, able to undergo surgery or medical intervention. This development has been primarily driven by systematic improvements in prenatal diagnosis, imaging technology, and surgical equipment.

Prerequisite guidelines for performing fetal surgery include:

The fetal lesion is accurately diagnosed;
The progression and severity of the anomaly is predictable and well under-stood;
Other severe associated anomalies that would contraindicate fetal intervention are excluded;
If left untreated before birth, the fetal abnormality would lead to fetal de-mise, irreversible organ damage, or severe postnatal morbidity, and, there-fore, intervening before birth would benefit the neonatal outcome; and
The maternal risk is acceptably infrequent.

Fetal surgery is broadly categorized into three types of intervention: minimally invasive procedures, open procedures, and intra-partum procedures.

Minimally invasive fetal procedures include (1) percutaneous interventions guid-ed by ultrasound, also known as fetal image–guided surgery for intervention or therapy (FIGS-IT), and (2) fetal endoscopic surgery.

Advantages of minimally invasive fatal surgeries include decreased risk of pre-term labour and delivery and possibility of a safe vaginal delivery in the present and future pregnancies.

Open fetal procedures involve a maternal laparotomy, a hysterotomy, and the need for intraoperative uterine relaxation. These involve increased risk of PPROM, oligohydramnios, preterm labor and delivery, uterine rupture, and fetal mortality, as well as risk of pulmonary edema, hemorrhage, membrane separa-tion, & chorioamnionitis.

Cesarean delivery is required after an open fetal procedure and for all future pregnancies owing to the increased risk for uterine dehiscence or rupture at the site of the hysterotomy.

For fetuses with known airway compromise or obstruction, an ex-utero intrapar-tum therapy (EXIT) procedure allows continued fetal support by the intact uteroplacental unit (placental bypass) while the fetal airway is secured or other procedures completed without the concern for postnatal respiratory compromise, hypoxia & asphyxia.

Common fatal indications that need interventions:

1. Anaemia & Intra uterine transfusion (IUT).
Rh D sensitisation, other red blood cell (RBC) antigens, parvovirus B19 infection, maternal-fetal hemorrhage, and homozygous thalassemia cause fetal anemia. IUT is not used before 18 to 20 weeks gestational age because reliable umbilical vein access is not possible. For cases requiring earlier intervention, intraperitoneal transfusion may initially be the intervention of choice.

2. Congenital Heart Defects.
The majority of fetal cardiac interventions 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, and (3) pulmonic valvuloplasty for pulmonary atresia or intact ventricular septum and hypoplastic right ventricles.

3. Obstructive Uropathy.
Most common cause: Posterior urethral valves in males, Urethral obstruction in females.
Treatment: Vesicoamniotic catheter shunt. This allows fatal bladder decompression in an effort to improve renal development and reduce plumonary hypoplasia associated with olioydramnios.

4. Twin reversed arterial transfusion sequence.
It is an abnormality of monozygotic twins, in which one of the twins has an absent or nonfunctioning heart and no share in the placenta. The nonviable twin is perfused with retrograde blood flow from the other twin that flows through arterio-arterial anastomoses; blood returns to the normal twin by venovenous anastomoses that bypass the placenta; resulting in lethal anomalies in the recipient twin and risk of high output cardiac failure in the normal twin. The goal of therapy is to interrupt the vascular communication between the two twins in an effort to prevent cardiac failure in the pump twin. Several approaches can accomplish these goals, including selective delivery of the nonviable fetus by hysterotomy, ligation, or transection of the cord using laser or bipolar diathermy; cord coagulation using coils or other thrombogenic material; and ablative therapy directed at the acardiac fetus near the base of the cord using laser, alcohol, or radiofrequency techniques.

5. Twin to twin transfusion syndrome.
Monochorionic twins share the same placenta and can have a significant degree of inter twin discordance.
Selective fetoscopic laser photocoagulation (SFLP) of the vascular anastomoses between the two twins is the best therapeutic approach for treating TTTS (stages II to IV) between 18 and 26 weeks gestation.

6. Congenital Diaphragmatic Hernia.
Fetal intervention for CDH aims to improve fetal lung development and prevent the morbidity of pulmonary hypoplasia.
Percutaneous endoscopic endotracheal intubation is used to place a small detachable occlusive balloon in the fetal trachea. It is deflated and removed before term with a second fetal endoscopic surgical techniques procedure.

7. Myelomeningocoele.
The rationale for fetal intervention for MMC is to improve functionality and quality of life. Prenatal repair for MMC is performed with an open fetal surgical technique that requires both maternal laparotomy and hysterotomy. MMC in utero surgery typically occurs mid–second trimester, before 26 weeks gestation.

8. Sacrococcygeal teratoma.
The larger tumors function as a substantial arteriovenous shunt that creates a low resistance state and leads to the development of high-output cardiac failure. They are at risk for intrapartum dystocia, tumor rupture with hemorrhage, and urinary obstruction. Cesarean delivery is frequently required.

Preoperative assessment and counselling.

Many considerations for peri-op management of women undergoing maternal-fatal surgery are similar to those for non obstetric surgery during pregnancy. Maternal safety is the primary focus when determining a plan that will optimise fetal outcome.

Optimum functioning of a fetal treatment program requires effective communication among the members of a multidisciplinary team, including surgeons, ultrasonographers, maternal fetal medicine physicians, anaesthesiologists, nurses, genetic counsellors, and social workers.

Maternal counselling regarding risks and benefits of the procedure should be thorough and unbiased. Discussions should focus on specific implications to the mother, the pregnancy, the fetus, postnatal care, future pregnancies, any data regarding intermediate and long-term outcomes for the proposed intervention, and all alternatives. Mothers should be informed about the planned timing and method of delivery, future reproductive implications, and—if a hysterotomy is planned—the risk for uterine rupture and need for cesarean delivery with this and all future pregnancies.

If the fetus is of viable gestational age, additional counseling is required about the mother’s wishes for possible emergent delivery and neonatal resuscitation in the event of unplanned fetal distress unresponsive to in utero treatment.

Intra operative management and considerations.

Fetal surgery involves two surgical patients. Consequently, in addition to maternal considerations for anaesthetic administration during pregnancy, it is essential to understand the impact of surgery and anaesthetic administration on fetal physiology, methods for fetal analgesia and anaesthesia, techniques for fetal monitoring, intra operative anaesthetic management, and postoperative care for both mother and fetus.

Fetal physiology and monitoring. During fetal surgery, procedural and pharmacologic interventions can adversely affect fetal physiology directly or affect it indirectly by alterations in uteroplacental or fetoplacental circulation and gas exchange. Appropriate fetal monitoring facilitates early intervention. Changes in anaesthetic technique, adjustment of maternal hemodynamics, and early initiation of in utero resuscitation of the fetus can decrease the risk for intra operative fetal hypoxia, hemodynamic compromise, or demise.

Fetal cardiac output depends primarily on heart rate. Fetal myocardium is less compliant than adult myocardium, with changes in preload having minimal effect on cardiac output. Constraining forces of the fluid-filled lungs also limit ventricular filling and restrict increases in cardiac output in response to additional preload.

Fetal blood volume increases during gestation, and approximately two thirds of the fetal-placental blood volume resides within the placenta.

Fetal lung epithelium produces more than 100 mL/kg/ day of fluid that fills the lungs and facilitates appropriate pulmonary growth and development. Excess lung fluid exits the trachea and is either swallowed or flows into the amniotic fluid.

Although fetal liver function is immature, coagulation factors are synthesized independent of the maternal circulation and do not cross the placenta. The serum concentrations of these factors increase with gestational age but fetal clot formation in response to tissue injury is decreased in contrast to that in adults throughout gestation.

Manipulation of the fetus or umbilical cord during open fetal procedures can affect fetal cardiac output, regional distribution of fetal circulation, or blood flow in the umbilical cord.

Fetal heart rate (FHR) monitoring is essential. Echocardiography, pulse oximetry, and ultrasound imaging of umbilical artery flow are the primary methods for fetal assessment. After exposure of the fetal head during an EXIT procedure, insertion of a fetal scalp electrode has been used successfully for FHR monitoring.

Intraoperative ultrasonography allows imaging of FHR, cardiac contractility, and cardiac filling, as well as Doppler assessment of umbilical cord flow.

When prolonged fetal bradycardia, Hb desaturation, or significant changes in umbilical artery flow dynamics occur during a fetal procedure, steps should be undertaken promptly to improve uterine perfusion, ensure the uteroplacental interface is intact, and relieve any compression of the umbilical cord or placenta. In some cases, ex utero fetal resuscitation may be necessary if the fetus was previously determined to be of a viable gestational age. In utero, the fetus is unable to thermoregulate and depends on maternal body temperature. Induction of general anesthesia, surgical exposure, and hysterotomy can reduce fetal temperature dramatically. Monitoring of temperature and maintenance of maternal euthermia with use of forced air warming likely improves fetal well-being during minimally invasive procedures. During open fetal surgery, use of warmed fluid for intrauterine irrigation and monitoring of both maternal core and amniotic fluid temperatures are also important.

Fetal Anaesthesia and Analgesia.

Anesthetic goals include prevention of fetal movement, inhibition of circulatory stress response, adequate pain relief, and potentially even fetal amnesia.

Opioid analgesics can be transferred to the fetus by maternal administration or direct intramuscular or intravenous umbilical cord administration using ultrasound guidance. For most invasive procedures that can cause noxious fetal stimulation, fetal intramuscular administration of fentanyl 10 to 20 μg/kg is used to provide analgesia immediately before the intervention. This can be achieved percutaneously using ultrasound guidance or under direct vision when a hysterotomy is performed. Prophylactic intramuscular atropine 20 μg/kg may be administered with opioids to minimize the risk for fetal bradycardia. Fetal movement can be prevented by intramuscular or umbilical vessel administration of muscle relaxant using ultrasound guidance. Drugs that have been used include pancuronium or vecuronium with doses of 0.3 mg/kg intramuscularly or 0.1 to 0.25 mg/kg intravenously. The onset of fetal paralysis varies with the specific drug and dose, but typically occurs in 2 to 5 minutes, with an approximate duration of 1 to 2 hours. Maternal administration and placental transfer of intravenous remifentanil provides adequate fetal immobility during fetoscopic interventions that involve only the umbilical cord or placenta.

For open fetal procedures, placental transfer of maternally administered general anesthesia with volatile anesthetics provides fetal anesthesia.

Volatile anesthetic for maternal anesthesia is used as the primary agent for fetal anesthesia during open fetal surgery or EXIT procedures. Some prefer to administer maternal remifentanil and nitroglycerin as part of the anesthetic for open fetal or EXIT procedures to decrease the amount of volatile anesthetic.

Management of minimally invasive procedures.

This involves the same considerations as for non obstetrics surgery during pregnancy. For most FIGS-IT procedures, use of monitored anaesthetic care with infiltration of local anesthetic into the abdominal wall provides an adequate level of maternal comfort. Administration of additional opioid, benzodiazepine, or other anesthetic can be used for maternal analgesia and anxiolysis, titrated to avoid deep sedation and the associated increased risk for pulmonary aspiration of gastric contents or respiratory compromise during pregnancy. In addition, use of supplemental anesthetic drugs possibly decreases the likelihood of fetal movement via placental transfer.

Anaesthesia choices for fetoscopic procedures:

Local anaesthesia.
Neuraxial techniques can be beneficial when multiple insertion sites are required, maternal immobility must be ensured, a mini-laparotomy must be per-formed, or concern exists about adequate patient comfort or appropriate patient cooperation during the procedure.
General anesthesia is rarely necessary for percutaneous procedures unless placental location and fetal orientation present potential technical difficulty or uterine exteriorization is needed.

In cases of IUT, cord blood sampling, or thoracic shunt placement, fetal movement may displace the needle or catheter and result in trauma, bleeding, or compromise of the umbilical circulation. Although maternally administered opioids and benzodiazepines can reduce fetal motion, they do not guarantee immobility for procedures directly involving the fetus. Fetal immobility can be safely achieved with direct fetal intramuscular or umbilical venous administration of muscle relaxant.

Weight-based unit doses of atropine 20 μg/kg and epinephrine 10 μg/kg should be immediately available in individually labeled syringes for direct administration to the fetus by the surgeon in emergent situations of fetal compromise. These medications require sterile transfer to the surgical field, meticulous labeling, and accurate dosing before commencement of the procedure. When emergently required, the surgeon can administer the indicated medication by intramuscular, intravenous, or intracardiac routes, depending on the procedure and urgency of the situation. If gestational development is compatible with extrauterine life, the anesthesiologist should be prepared to emergently provide general maternal anesthesia, and the obstetric team should be prepared to perform an emergency cesarean delivery if fetal bradycardia persists despite efforts to resuscitate in utero.

Management of Open Procedures.

General anesthesia is primarily employed for fetal surgery requiring a hysterotomy. Open fetal surgery requires profound uterine relaxation, often entails additional fetal monitoring beyond intermittent ultrasonography; involves more fetal surgical stimulation, fetal hemodynamic perturbation, and risk for fetal compromise; and requires direct administration of some drugs to the fetus. The anesthesiologist and other team members should be prepared for significant maternal and fetal blood loss, and the need for maternal and fetal resuscitation, including emergent delivery.

A volatile anesthetic is commonly administered to provide maternal and fetal anesthesia, as well as uterine relaxation, which may require a concentration of more than 2 MAC. Single, weight-based, unit doses of medications for fetal analgesia and muscle relaxation should be available for administration by the surgical team. In addition, resuscitation medications (atropine 20 μg/kg, epinephrine 10 μg/kg, and crystalloid 10 mL/kg) should be prepared preoperatively for immediate availability in the emergent treatment of intraoperative fetal hemodynamic compromise. Cross-matched blood should be available for maternal transfusion. For procedures with a high risk for fetal hemorrhage, appropriate blood for fetal transfusion (i.e., O-negative, cytomegalovirus-negative, irradiated, leukocyte-depleted, maternally cross-matched) should be readily available.

Drugs and approaches should be used to minimize aspiration of gastric contents. Uterine tocolytics (i.e., indomethacin) should be given to the mother preoperatively. An epidural catheter is placed preoperatively for administration of postoperative analgesia. FHR is assessed and baseline cardiac echocardiography and ultrasound imaging of umbilical cord flow characteristics are performed before anaesthetic induction and are intermittently reevaluated throughout the initial period of anaesthetic administration to assess the effect on the fetus of the maternal positioning, anaesthetic administration, and any maternal hemodynamic changes. The gravid uterus is displaced leftward and general anaesthesia is induced with a rapid sequence technique identical to patients undergoing non obstetric surgery during pregnancy.

After anaesthetic induction and before maternal skin incision, conventional concentrations of anaesthetics are administered to the mother (~1 MAC); ventilation is controlled to maintain eucapnia; and fetal attitude, presentation, and placental location are reassessed by ultrasound. An invasive maternal intra arterial pressure catheter is placed when administration of a nitroglycerin infusion is planned for uterine tocolysis. A large-bore venous catheter is placed for treatment of unexpected excessive hemorrhage. However, intravenous fluids administered to the mother are minimized (<2 L) to decrease the risk for perioperative pulmonary edema associated with the use of tocolytics, such as magnesium sulfate or administration of large doses of nitroglycerine during fetal surgery.

Typical maternal hemodynamic goals include maintaining systolic arterial blood pressure within 10% of baseline values and mean arterial pressure greater than 65 mm Hg. Phenylephrine administration can be used to treat maternal hypotension with minimal changes in the fetal acid-base status.

Administration of a maternal nondepolarizing muscle relaxant is usually unnecessary with administration of appropriate concentrations of volatile anesthetics, but may be used to improve operative conditions. If it is used, appropriate neuromuscular monitoring should be employed to carefully assess neuromuscular function with appropriate pharmacologic reversal of blockade before tracheal extubation, particularly with concurrent use of magnesium sulfate.

Before skin incision, the inspired concentration of volatile anaesthetic is increased, and before uterine incision, the volatile anaesthetic end-tidal concentration is further increased (≥2 MAC) to provide profound uterine relaxation. If uterine relaxation is inadequate, administration of additional volatile agent (up to 3 MAC) or intravenous nitroglycerin as an infusion or in small boluses (50 to 200 μg) is used. For rare patients with contraindications to either volatile anesthetics or induction of general anaesthesia, a neuraxial technique in conjunction with intravenous administration of nitroglycerin in doses upto 20 μg/kg/min has been used successfully.

Periodic ultrasonography is used to assess FHR and fetal cardiac function. In some open fetal procedures, pulse oximetry can be employed after the hysterotomy. An opioid and a muscle relaxant can be administered to the fetus intramuscularly either before uterine incision with ultrasound guidance of the injection needle or under direct vision after uterine incision. Intramuscular atropine also can be administered concurrently to reduce opioid-induced fetal bradycardia.

After uterine exposure and ultrasound placental mapping, a small hysterotomy is created away from the placenta. A stapling device with absorbable lactomer staples is used to extend the incision. The staples prevent hemorrhage from the relaxed uterus and seal the amniotic membranes to the uterine endometrium. Uterine blood loss can be rapid and difficult to estimate. Vigilant observation of the surgical field and careful maternal monitoring are essential to avoid missing occult hemorrhage. Lost amniotic fluid is replaced with warmed crystalloid to bathe the exposed fetus. Intrauterine temperature is closely monitored to prevent hypothermia and associated fetal circulatory compromise.

For fetal mass resections or other open procedures with high risk for significant fetal blood loss, an intravenous catheter should be placed in a fetal limb for blood and fluid transfusions. The umbilical vein may be used for this purpose. All blood or fluids transfused to the fetus should be warmed.

In the rare event of maternal hemodynamic collapse, if maternal resuscitation has been unsuccessful in restoring adequate maternal hemodynamics after 4 minutes, the fetus should be delivered emergently to relieve aortocaval compression, improve maternal resuscitation efforts, and increase the chance for maternal survival. A neonatologist and neonatal resuscitation team should be readily available in case of emergency delivery, and newborn resuscitation should proceed according to the current recommended guidelines.

After completion of the fetal procedure, an initial dose of magnesium sulfate 4 to 6 g intravenously over 20 minutes is typically administered during uterine closure to reduce myometrial contractility, followed by an infusion of 1 to 2 g/hr into the postoperative period. The inspired concentration of volatile anesthetic or intravenous nitroglycerin infusion is significantly decreased or discontinued after the magnesium sulfate bolus is complete. Maternal anesthesia is maintained with epidural anesthesia, supplemented by administration of intravenous opioid, inhaled N2O, and/or intravenous propofol; this allows adequate time for elimination of the volatile agents during surgical closure of the abdominal incision. The mother’s trachea is extubated after she awakens and after confirming adequate neuromuscular recovery and hemodynamic stability.

Postoperative management and considerations.

In addition to postoperative concerns associated with a cesarean delivery (i.e., pain management, prevention of venous thromboembolism, monitoring for hemorrhage, avoiding wound infection), postoperative care of patients undergoing fetal surgery also focuses on tocolysis and fetal monitoring.

Minimally invasive procedures – tocolysis is usually not needed. For more invasive percutaneous procedures, some give agents like indomethacin, more drugs are rarely needed. Open fetal surgeries, require uterine monitoring for 2-3 days. Magnesium sulphate infusions are continued. Additional agents like indomethacin, terbutaline, nifedipine are often necessary. Administration of indomethacin requires periodic monitoring by fetal echocardiography because premature closure of the ductus arteriosus is a known complication of therapy.

The fetus is evaluated postoperatively by ultrasonography. Potential fetal morbidity includes infection, fetal heart failure, fetal intracranial hemorrhage, and fetal demise. If maternal pulmonary edema is suspected, a chest radiograph should be obtained.

For minimally invasive procedures, satisfactory postoperative analgesia is typically achieved by administration of oral opioid-based pain medications. For open procedures, postoperative epidural analgesia can be provided for several days using a dilute solution of local anaesthetic and opioid. Inadequate postoperative pain control can increase plasma oxytocin levels and increase the risk for preterm labor.

After open fetal procedures, patients are at high risk for PPROM, preterm labor, infection, and uterine rupture. In addition to these risks, periodic assessment of fetal wellbeing, growth, and integrity of the pregnancy necessitate the mother to remain near the fetal treatment institution for the first few weeks after the procedure.

Management of exutero intrapartum treatment procedures.

Fetal indications for EXIT procedures include conditions that compromise the fetal airway, such as large neck masses, congenital high airway obstruction, or severe micrognathia, intrathoracic mass resection, in separation of conjoined twins, and as a bridge to extracorporeal support. The EXIT procedure allows the fetus to remain supported by the placental unit with adequate oxygenation and perfusion while surgical repair and resuscitation interventions are performed in a controlled manner.

The primary goals of the EXIT procedure are to maintain a prolonged state of uterine relaxation, to delay placental separation, and to sustain placental-fetal perfusion. These procedures are usually performed under general anaesthesia, employing high concentrations (≥2 MAC) of volatile anaesthetic to ensure uterine relaxation. Neuraxial anaesthesia in combination with remifentanil, nitroglycerin, or both also has been used successfully. The overall preoperative and intraoperative approach for anesthetic management is similar to that previously described for open fetal surgery.

They include possible placement of an epidural catheter for postoperative analgesia, large-bore intravenous access, invasive monitoring readily available or placement of an intra-arterial catheter, possible need for uterotonic drugs after delivery of the placenta, and cross-matched maternal blood in the operating room.

The primary difference occurs after delivery of the fetus, when uterine relaxation is no longer required. Thus, after delivery of the neonate, anaesthetic management becomes similar to management of a cesarean delivery with general anaesthesia.

In addition to fetal ultrasonography, a pulse oximeter and ETCO2 indicator are used to monitor the fetus and assist with confirmation of a secured airway. Similar to open fetal surgery, weight based doses of atropine, epinephrine, and calcium are prepared for possible emergency fetal resuscitation. A sterile fetal ventilation circuit with an air/O2 source and manometer is prepared in addition to multiple sizes of endotracheal tubes, laryngoscopes, and neonatal-sized laryngoscope blades for fetal tracheal intubation. Sterile tourniquets, intravenous catheters, crystalloid and blood(i.e., O-negative, CMV-negative, leukocyte depleted, maternally cross-matched) should be available for fetal venous access and volume replacement if needed.

After assessment of appropriate uterine relaxation, the placental border is determined by ultrasonography. A small initial hysterotomy is extended outside the placental border with a stapling device to prevent excessive blood loss. If the EXIT procedure is performed to facilitate fetal intubation or neck mass resection, only the fetal head and shoulders are initially delivered. For more extensive procedures requiring access to the thorax or other anatomic locations, the entire body may be delivered.

Depending on the indication, the duration of an EXIT procedure ranges from a few minutes to several hours. Anesthetic techniques have successfully provided safe maternal and fetal anesthesia with uterine relaxation and uteroplacental stability over several hours. Before ventilation of the fetal lungs, fetal oxyhemoglobin saturation is typically 40% to 70%. After initiating ventilation of the fetal lungs, oxyhemoglobin saturation should increase significantly to above 90%. When fetal lung ventilation fails to result in an appropriate increase in oxyhemoglobin saturation, this represents an indication for ECMO initiation before clamping the umbilical cord and fetal delivery. An ETCO2 indicator is also beneficial in confirming correct placement of the endotracheal tube. If needed, pulmonary surfactant may be administered once the endotracheal tube is placed. Once the fetus is delivered, the inspired concentration of the volatile agent is significantly decreased, the nitroglycerin infusion stopped, or both to allow the uterus to contract and diminish the risk for maternal hemorrhage. Oxytocin is routinely administered and additional uterotonic drugs are given when necessary. Once the patient is hemodynamically stable with appropriate uterine tone, epidural analgesia may be initiated. Only the results of animal research and descriptive summaries of clinical series currently guide clinical anesthetic care for fetal surgery. Well-organized, multidisciplinary, professional, and comprehensive fetal treatment programs at academic medical centers facilitate the sustained effort to innovate new techniques, challenge dogma, and ensure ongoing success. Further rigorous research is needed to determine optimal anesthetic techniques to ensure maternal and fetal cardiovascular stability, to evaluate the best gestational age of anesthetic exposure, to assess the impact of anesthetic management strategies on myometrial tone and uteroplacental perfusion, and to improve our ability to determine the adequacy of fetal anesthesia to cause immobility and blockade of the fetal stress response. More collaborative clinical investigation among international research centers will guide the evolution of prenatal fetal therapy.

References:

Anaesthesia for petal surgery and other fetal therapies. Mark D. Rollins. Millers Anaesthesia 8th edition: 23590-2385
Anaesthesia for fetal surgery and other intrauterine procedures. Mark D. Rollins, Mark A. Rosen. Chestnut’s Obstetric Anaesthesia Fifth edition. 128-147
Jelin E, et al: Fetal Diagn Ther 27:138, 2010.
Deprest JA, et al: Fetal Diagn Ther 29:6, 2011.
van de Velde M., De Buck F: Fetal and Maternal Analgesia/Anesthesia for Fetal Procedures. Fetal Diagn Ther 2012;31:201–209