Anaesthesia for fetal surgery

The National Institute of Child Health and Development was asked recently to predict health care in the new millennium. The Institute predicted, by the year 2020, that the routine diagnosis and treatment of congenital malformations in utero before secondary morbidity would develop (1). Fetal surgery was specifically mentioned as standard therapy for most disabling malformations that are currently treated in young infants. With advances in prenatal ultrasonography techniques, many structural anomalies can now be identified in the first trimester, affording the opportunity for invasive fetal therapy and treatment before irreversible damage occurs (2). If this proves to be the case, anaesthesia for neonatal surgical emergencies will not be as common as it is today. This paper will review the indications, anaesthetic issues and postoperative pain management for fetal surgery as practiced in the year 2002 (2). The first successful fetal procedure was performed in 1963 by Sir William Liley, consisting of an intraperitoneal blood transfusion to a fetus affected with erythroblastosis fetalis (3). Years of animal investigations followed, most notably by Dr Michael Harrison and his team at the University of California, San Francisco (4-8). Surgical, anaesthetic and tocolytic techniques were first developed in nonhuman primates and then refined in fetal lambs and rhesus monkeys. This process ultimately led to the surgical techniques used for human fetal surgery today. To date, three medical institutions perform the majority of fetal surgical procedures in the USA: The Children's Hospital of Philadelphia, Vanderbilt University Medical Center and University of California, San Francisco. These fetal teams have applied the knowledge acquired from years of animal research to human patients, performing human fetal surgery since the early 1990s. Fetal surgery has now become a treatment option for certain life-threatening diseases with promising results. Anaesthesia for fetal surgery involves two patients simultaneously, the mother and the fetus. Anaesthesia for fetal surgery differs from that for maternal surgery (e.g. Caesarean sections, cholecystectomy in the parturient) and fetal therapy (e.g. amniotic fluid reduction) (9). In fetal surgery, the fetus and mother are both active recipients of surgery whereas, in maternal surgery, the mother is an active recipient while the fetus is a bystander. In fetal therapy, the mother is a bystander while the fetus is an active recipient of therapy. The distinction will likely become more important as the mechanism of labour becomes better understood (10-12). Fetal surgery consists of open or minimally invasive procedures. Open procedures require a hysterotomy on the mother and major airway, thoracic, cardiovascular and neurological procedures on the fetus. Minimally invasive fetal procedures include insertion of stents or shunts, occlusion or coagulation of fetoplacental structures, and transfusion of medications or blood products directly into the fetus. These procedures may be performed with sedation, regional anaesthesia or general anaesthesia, depending on maternal and fetal factors. The mother and fetus are considered appropriate for surgery only when the risk of death or severe disability to the fetus is greater than no intervention and the risk to the mother remains low (Table 1). Hydrops fetalis, a condition characterized by abnormal accumulation of fluid and oedema in the fetus, is the common final pathway in a number of pathological conditions. Several anatomical anomalies diagnosed in utero progress to hydrops with almost certain fetal demise. These anomalies are considered for fetal surgical intervention. Contraindications for fetal surgery include a lethal or disabling genetic disease in the fetus, other structural anomalies in the fetus, or a serious medical disease in the mother (e.g. preeclampsia, mirror syndrome) (6, 9, 13). After open fetal surgery, this pregnancy and all subsequent pregnancies require delivery by Caesarean section because the hysterotomy incision precludes a trial of labour. In contrast, fetal surgery using minimally invasive techniques permits vaginal delivery. Thoracic diseases considered for fetal surgery include congenital cystic adenomatoid malformation (CCAM) and pulmonary sequestration in which the mass is increasing in size and hydrops is present (14). These masses and other intrathoracic masses can compress the heart and lungs, resulting in heart failure and severe pulmonary hypoplasia. The goals of these operations are to remove the mass to allow the lung to grow and to unobstruct systemic venous return to restore cardiovascular function (Figure 1). The longer the fetus remains in utero after surgery, the better the compensatory lung growth and chance of postnatal viability. Resection of the lesion through a thoracotomy usually takes place at 18–25 weeks of gestation (6, 8, 14). Resection of CCAM: operative exposure. Airway diseases for fetal surgery include large neck masses with anticipated airway obstruction and difficult intubation at birth, and congenital high airway obstruction syndrome (CHAOS). In these diseases, the airway is secured before birth with the EXIT procedure (ex utero intrapartum therapy) (6, 8, 9, 14). The EXIT procedure entails delivering the fetal head through a controlled hysterotomy and managing the airway by direct laryngoscopy, bronchoscopy and intubation while fetal gas exchange is maintained via the placenta. If an orotracheal tube cannot be inserted, a tracheostomy is performed (Figure 2). In some circumstances, fetal gas exchange can be supported by ex utero placental circulation for over 60 min, affording ample time to secure the airway and partially resect the mass if needed. The mass is usually excised immediately after birth in an adjacent operating room by a separate surgical and anaesthesia team after airway evaluation, intubation and separation from the maternal circulation. The EXIT procedure is scheduled as close to term gestation as possible to avoid the problems associated with prematurity. However, the EXIT procedure may be earlier for CHAOS because of hydrops fetalis. In the latter circumstance, there is complete airway obstruction in utero, resulting in fluid accumulation in the developing lungs, pulmonary engorgement with compression of the heart and decreased venous return, leading to hydrops. EXIT procedure. Twin syndromes considered for fetal surgery include twin reversed arterial perfusion sequence (TRAP) and twin–twin transfusion (6, 9). In TRAP, one fetus has a lethal disease (e.g. acardiac or acephalic), which threatens the viability of the other fetus from high-output cardiac failure where hydrops ensues from the dual cardiac output required to support both twins. Fetal surgery involves ligation of the umbilical cord of the donor twin, which eliminates the source of the pump twin's high-output failure and the cord-ligated twin expires and mummifies in utero. This procedure is usually performed at 18–25 weeks of gestation. Birth of the live and mummified twins usually occurs near term by spontaneous vaginal delivery. In twin–twin transfusion syndrome (TTTS), monozygotic, monochorionic twins share communicating placental circulations. An imbalance of blood flow between them results in polyhydramnios in one twin (recipient) and oligohydramnios, and often growth retardation in the other (donor). The cause of this imbalance is thought to be arteriovenous anastomoses deep within the placenta that connect to superficial afferent and efferent vessels on the surface of the placenta. With laser ablation of these superficial vessels, survival and outcome of these twin fetuses may improve. Fetal surgery is indicated if the ratio of donor/recipient twin blood flow exceeds 0.7, because twins with this ratio develop cardiac failure, hydrops, neurological complications, preterm delivery or intrauterine demise (15). Of all the fetal diseases, repair of meningomyelocele has recently received the most attention, in both lay press and professional publications (8, 16-21). The objective for fetal meningomyelocele surgery is to prevent shunt-dependent hydrocephalus and further loss of spinal cord function. A growing body of evidence supports a dual causation of the loss of spinal cord function comprising an initial embryonic defect and a secondary injury of the neural tissue exposed to amniotic fluid throughout gestation. The contribution of the secondary injury relative to the initial embryonic defect remains unknown and is difficult to establish in human studies. However, an unexpected result of fetal closure of the meningomyelocele has been reversal of hindbrain herniation (Arnold Chiari defect) and a lower incidence of shunt dependent hydrocephalus. This benefit appears to result from the restoration of cerebrospinal fluid flow dynamics in utero after the spinal defect is closed. Fetal closure of the meningomyelocele through an open hysterotomy currently takes place at 22–25 weeks of gestation (Figure 3), although in the future closure may occur earlier in gestation to improve outcome (16, 17, 21). Myelomeningocele in 22-week-old fetus prior to repair. Sacrococcygeal teratomas have also been removed in utero (6, 9, 22). These are highly vascular, benign tumours located near the sacrum. Large sized vascular defects can precipitate high-output cardiac failure and fetal hydrops, as well as obstruct urine output and cause oligohydramnios. Fetal surgery seeks to restore cardiovascular stability through complete or partial resection of the teratoma (Figure 4). The procedure usually occurs at 20–25 weeks of gestation. Sacrococcygeal teratoma in 24-week-old fetus prior to surgical repair. Other fetal diseases under consideration for surgery include posterior urethral valves with bladder outlet obstruction, aqueductal stenosis of the fourth ventricle with resultant hydrocephalus and diaphragmatic hernia with liver in the chest (5, 6, 8, 23, 24). Over a decade ago, fetal surgery was performed for these diseases with dismal results. However, improved understanding of the pathophysiology, preoperative evaluation and surgical techniques has rekindled interest in fetal surgery for these disease processes. Suspicion of fetal disease is usually raised by the detection of maternal polyhydramnios or oligohydramnios on a routine ultrasound examination during a prenatal visit. Medical evaluation of the fetus includes echocardiography to assess cardiovascular function, whole body ultrasound to delineate the defect and severity of hydrops and magnetic resonance imaging to detail the anatomy (25). A fetal karyotype analysis is performed for defects associated with genetic syndromes. The mother undergoes a complete history and physical examination, blood chemistry analysis and complete blood count, chest X-ray and electrocardiogram. The parents also undergo a psychosocial evaluation. After these evaluations, the fetal team convenes to discuss eligibility for surgery. The team consists of paediatric surgeons, perinatologists, anaesthesiologists, radiologists, geneticists, nurses, social workers and financial advisors. The team then meets with the parents to discuss the procedure and risks. Parents are given time to consider the risks and benefits of fetal surgery and to discuss the uncertainty of the fetal outcome for most procedures. Best surgical results require intervention early in gestation before irreversible damage has occurred so that sufficient in utero growth and healing can take place. After 30 weeks of gestation, it is usually too late for fetal surgery. These considerations include maternal, uteroplacental and fetal factors. The anaesthesiologist must balance these factors for optimal outcome during fetal surgery. Virtually every organ system in the mother undergoes physiological changes during pregnancy (26-28). Those changes of particular importance to the anaesthesiologist are well known and include alterations in the gastrointestinal, pulmonary, cardiovascular and central nervous systems. The pregnant patient for fetal surgery is at increased risk of aspiration of gastric contents for several reasons. As the uterus enlarges, the gastroesophageal junction is shifted upward and posterior, resulting in incompetence. The pylorus is also displaced, slowing gastric emptying rates. With secretion of gastrin from the placenta, the acid content within the stomach is elevated. These alterations can be exaggerated with obesity, multiple gestations and hydramnios. For these reasons, all pregnant patients must be considered at increased risk of aspiration and appropriate measures executed to minimize this risk. Respiratory alterations during pregnancy are of particular significance to the anaesthesiologist (26-28). Minute ventilation is increased by 50% and oxygen consumption is increased to a lesser degree by the end of the first trimester. Because functional residual capacity decreases by 20%, these changes make the pregnant patient susceptible to hypoxia during anaesthetic induction. Mucosal capillary engorgement may also create difficulty with intubation of the trachea. It is also important to recognize that increased minute ventilation results in a normal resting PaCO2 of 3.7–4.3 kPa (28–32 mmHg). Overzealous ventilation can further decrease the PaCO2, resulting in a leftward shift of the oxyhaemoglobin curve, and may reduce the availability of oxygen to the fetus. With hyperventilation, a reduction of maternal cardiac output and uterine blood flow may also occur. Supine hypotension syndrome can occur in pregnant patients from compression of the inferior vena cava by the gravid uterus (26-32). This compression can lead to a marked decrease in systemic venous return, as well as an increase in uterine venous pressure, and thus a decrease in uterine perfusion pressure, placing the fetus at risk for hypoxia. Compression of the aorta can further decrease uterine perfusion pressure by decreasing uterine blood flow. Therefore, it is imperative to provide left uterine displacement to minimize this risk. Pregnancy is known to decrease minimal alveolar concentration (MAC) (13, 26-32). This may be the result of increased levels of progesterone and beta endorphins. The epidural space is decreased by epidural venous engorgement. This may result in a greater chance of intravascular epidural placement, and less local anaesthetic to achieve the same level of epidural block compared with nonpregnant patients. Total protein, serum albumin and plasma cholinesterase levels decrease during pregnancy. The resulting decrease in oncotic pressure from alterations in total protein make the pregnant patient vulnerable to fluid retention and pulmonary oedema and may prolong the effect of succinylcholine. Uteroplacental factors considered for fetal surgery include the location of the placenta and cord structures in the uterus, of uterine and placental blood uterine for fetal surgical and placental of labour in the postoperative and placental of during and after fetal surgery. are of uterine (Figure complete can be with anaesthetic of However, these high of decrease uteroplacental perfusion and fetal cardiac output The effect of on uterine with from and and and (9). blood flow is the major of placental blood flow and to the of the placenta factors that decrease uterine blood flow during fetal surgery may fetal well These factors include increased uterine maternal hypotension or and from As decrease maternal arterial pressure and uteroplacental blood flow Fetal arterial and decrease as increase in the mother (Figure To uteroplacental maternal arterial pressure must be maintained during the In of can cause this with a marked reduction in uterine blood flow. An is which and has minimal on uterine blood flow. of on uterine blood fetal and fetal oxygen in with from and and and (9). of placental are used by the anaesthesiologist during fetal surgery. (e.g. the placental by active and via of within the space (26-32). In placental and of the placental an important in of Those that are not and of low the placenta. this and placental of occurs of anaesthetic occurs more in the fetus that the mother (Figure than Because of the by the fetus compared with the it is important to the of the fetal surgical procedure to achieve sufficient anaesthetic in the fetus. in the fetus is less that that in the and fetal is well that to uterine maternal anaesthesia and uterine results in fetal anaesthesia in mother and fetus in with from and and (9). The organ system function (e.g. cardiovascular fetal surgical patients at high anaesthetic risk. Fetal is decreased compared with the and is low in the fetal surgery patient (e.g. decreased coagulation in the fetus to during surgery. Therefore, the fetus may require a blood transfusion in procedures usually associated with a minimal blood Other include which to fluid and The of decreased and fluid loss the fetus to and in the fetus compensatory in the of (9). decreases fetal blood flow to the placenta, which in decreases fetal surgery, all of these factors place the fetus at high risk for low cardiac output and fetal and are present in the fetus by the fetal surgery patient anaesthesia to prevent of pain and to Because the of occurs more in the fetus than in the it is imperative to well in the of the surgical incision on the fetus (Figure of to the mother more than fetal anaesthesia as as uteroplacental gas exchange is The fetus given the of in is of directly to the fetus may many and provide postoperative to the mother will the fetus and also provide Open fetal surgery general anaesthesia because both mother and fetus must be and the uterus must be Fetal surgery patients are usually the of surgery. 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