Mother

Fetal interventions have been successfully performed with various anesthetic techniques; both maternal and fetal anesthetic requirements must be considered and may, in fact, be quite different. With some endoscopic interventions, the site of surgical intervention is not innervated; thus the fetus may not sense a noxious stimulus, and its anesthetic requirements are presumably minimal. Nevertheless, fetal immobility remains essential to procedural safety and success. Other interventions may require that a needle be inserted into the fetus, which may elicit a noxious stimulus and possibly even cause pain. Open procedures can produce significant noxious stimuli. In addition to surgical demands, each mother and fetus exhibit a unique physiologic, pharmacologic, and pathophysiologic profile; the anesthesiologist must evaluate the advantages and disadvantages of each anesthetic technique and select the safest anesthetic.²

Fetus

Maternal anesthetic techniques that do not include inhalational anesthetics may not provide adequate analgesia and/or anesthesia for the fetus. However, fetal analgesia and anesthesia may also be accomplished by delivery of anesthetics and analgesics directly to the fetus. Potential methods include transplacental, direct intramuscular, direct intravascular, and intraamniotic administration; each route of administration has advantages and disadvantages that can have a direct impact on overall outcome.

Transplacental Access

Many fetal interventions (open or endoscopic) employ transplacental drug administration to provide anesthesia and analgesia for both mother and fetus. Many, but not all, drugs cross the placenta via Fick’s law of passive diffusion (Fig. 37-1). Lipid solubility, the pH of both maternal and fetal blood, the degree of ionization, protein binding, perfusion, placental area and thickness, and drug concentration are factors that influence the extent of transplacental drug diffusion.¹³ The most obvious disadvantage with this approach is that the mother must be exposed to every drug that the fetus is intended to receive, often at large concentrations, to achieve adequate drug concentrations in the fetus. In addition, the uptake of drugs may be impaired if there is reduced placental blood flow. This has implications for successful anesthesia and analgesia both in terms of the delivered fetal dose and the time interval that must be allowed from maternal administration to the start of the fetal intervention. All inhaled anesthetics cross the placental barrier, but uptake in the fetus is slower than in the mother.¹³ However, this is offset by the reduced minimal alveolar concentration (MAC) for anesthesia in the fetus, resulting in a similar onset of anesthesia as in the mother.² Fetal anesthesia is also important to reduce the fetal stress response, which, through catecholamine release, can reduce placental blood flow and exacerbate any asphyxia.^14–17

FIGURE 37-1 Fick’s law of passive diffusion described at the intervillous space (IVS). D, Membrane thickness; K, diffusion constant of the drug; M, membrane surface area; Q/t, rate of diffusion.

Pathologic Lung Development

In the context of fetal interventions, there are two important causes of respiratory morbidity to consider: insufficient amniotic fluid and prematurity. With both, the timing of the insult in terms of the stage of lung development is critical to estimating the degree of likely morbidity. Deficiency of amniotic fluid may result from prelabor premature rupture of the amniotic membranes (PPROM), which may be spontaneous or iatrogenically induced either directly through trauma or by introducing infection into the uterus. Small amniotic fluid volume may also be secondary to reduced fetal urine output, from either poor renal function (e.g., with renal agenesis or urinary tract obstruction) or growth restriction secondary to placental insufficiency. Amniotic fluid deficiency contributes to pulmonary hypoplasia. In general, the likelihood of pulmonary insufficiency is inversely related to gestation at membrane rupture, a long latency to delivery, and the amount of residual amniotic fluid.^21–23 The risk is relatively small if PPROM occurs after 24 weeks gestation,²⁴ as demonstrated by one series of fetuses with PPROM before 26 weeks reporting pulmonary hypoplasia in 27% of fetuses.²⁵ In contrast, with severe oligohydramnios of more than 2 weeks duration after PPROM arising before 25 weeks gestation, the predicted neonatal mortality exceeds 90%.²⁶

Studies in sheep show that oligohydramnios causes spinal flexion, which compresses the abdominal contents, displacing the diaphragm upward and thus compressing the developing lungs.²⁷ This increase in the pressure gradient between the lungs and the amniotic cavity causes a net loss of lung fluid through the trachea, preventing lung expansion.²⁷ Lung fluid produced in the airways is thought to act as a stent for the developing lungs.²⁸ Normally, it passes out through the trachea and is either swallowed or passes into the amniotic cavity. Ligation of the trachea causes lung hyperplasia²⁹ or ipsilateral lung hyperplasia if a main bronchus is ligated.³⁰ Experimental drainage of amniotic fluid in animals has been shown to result in pulmonary hypoplasia.³¹ Later restoration of amniotic fluid prevents the onset of pulmonary hypoplasia.³² There is evidence to support amnioinfusion in humans to maintain fluid volumes around the fetus after PPROM, in an effort to improve lung development.^26,33

Surfactant is a complex of phospholipids secreted by type II alveolar cells, which reduces lung surface air tension, thereby preventing the lungs from collapsing at low volumes. Glucocorticoids, thyroid hormone, and β-adrenergic agonists stimulate surfactant synthesis. It is first detected in the lungs around 23 weeks gestation, but mature levels necessary for unassisted ventilation are not present until about 34 weeks. The degree of lung maturity can be evaluated by amniocentesis using the lecithin to sphingomyelin ratio or, more recently, by the lamellar body count.³⁴ Acceleration of surfactant synthesis may be achieved with corticosteroids administered to the mother.³⁵

FETAL Cardiovascular Development

The differences between the fetal and postnatal circulations are complex (Fig. 37-2). In the fetal circulation, oxygenated blood returns from the placenta via the umbilical veins and ductus venosus (bypassing the liver) into the right atrium. At 20 weeks, 30% of the umbilical venous return (40 to 60 mL/kg/min) is shunted through the ductus venosus.³⁶ This flow decreases over the second half of gestation as hepatic blood flow increases so that, by term only 20% of umbilical venous return (less than 20 mL/kg/min) is shunted through the ductus venosus.³⁶ Hypoxia and hemorrhage increase the resistance in the liver, shunting a greater proportion of blood toward the brain and heart via the ductus venosus.³⁷ The proportion of blood that perfuses the liver, which exits 15% less saturated in oxygen, rejoins the ductus venosus blood in the inferior vena cava. However, this deoxygenated blood has less kinetic energy and flows more slowly into the right atrium toward the right ventricle.³⁷ The greater-velocity oxygenated blood from the ductus venosus is preferentially directed through the foramen ovale into the left side of the heart and out via the aortic arch to the developing head and upper body. The integrity of the foramen ovale is thus imperative. Blood returning from the placenta along the umbilical vein is 80% to 85% saturated. Despite this streaming within the right atrium, some mixing does occur, resulting in blood that is 65% saturated in the ascending aorta. The blood in the left ventricle, however, is 15% to 20% more saturated than the blood in the right ventricle. Most of the deoxygenated blood in the right ventricle bypasses the high-resistance pulmonary vasculature to enter the ductus arteriosus, and from there the descending aorta to supply the lower body, or pass via the umbilical arteries for reoxygenation in the placenta. In contrast to extrauterine life, when the two ventricles function in series and thus have equal outputs, before birth they function in parallel. Their outputs, therefore, do not have to be equal and, in fact, are not. In the third trimester, the right side of the heart has a greater output, as determined by Doppler ultrasonography studies, showing a 28% greater stroke volume than the left side.³⁶

FIGURE 37-2 Fetal circulation. Red arrows represent flow of oxygenated blood and blue arrows represent flow of deoxygenated blood. Black arrows indicate direction of blood flow and represent travel of blood from the central circulation through capillary membranes and return to central circulation. Shading (from red to purple to blue) represents the corresponding relative oxygenation of the blood at that site, from oxygenated to deoxygenated. Note the mixing of blood as the ductus venosus delivers oxygenated blood from the placenta to the central fetal circulation and the progressive desaturation of blood in the fetal aorta secondary to shunts, consumption, and the return of deoxygenated blood from the fetal pulmonary circulation.

Fetal heart rate (FHR) is maintained above the intrinsic rate of the sinoatrial node by a combination of vagal and sympathetic inputs, as well as circulating catecholamines.^38–40 FHR decreases throughout gestation,^41,42 accompanied by an increase in stroke volume as the heart grows. Hypoxic stress in late gestation produces a reflex bradycardia, with a normal heart rate or tachycardia developing a few minutes later. The chemoreceptor reflex nature of the bradycardia is demonstrated by its abolition after section of the carotid sinus nerves.⁴³ The later tachycardia is a result of an increase in plasma catecholamines causing β-adrenergic stimulation.⁴⁴ Hemorrhage can also produce increases in FHR, probably via a baroreceptor reflex.

Cardiac output in the fetus is determined largely by heart rate.⁴⁵ The combined ventricular output of the left and right ventricles in the human fetus is 450 mL/kg/min.⁴⁶ During development, the ability of the fetus to increase stroke volume is limited by a reduced proportion of functioning contractile tissue and a limited ability to increase the heart rate because of a relatively reduced β-adrenergic receptor density and immature sympathetic drive. Thus if blood volume is reduced by hemorrhage, the heart cannot compensate by increasing stroke volume, or, conversely, if volume is increased, the walls are less able to distend and cardiac efficiency is reduced (although this second effect is reduced substantially by the huge, relatively compliant placental circulation). Thus the only way for the fetus to increase cardiac output is to increase heart rate. Despite this homeostatic limitation, the fetus is able to withstand significant hemorrhage. Sheep studies have shown that the fetal lamb can restore arterial blood pressure and heart rate very quickly, without any measurable disturbance in acid-base balance after acute loss of 20% of their blood volume.⁴⁷ Even after a 40% reduction in blood volume, the ovine fetal blood pressure recovers to normal within 2 minutes and the heart rate within 35 minutes.⁴⁸ Oxygen delivery to the brain and heart is maintained secondary to vascular redistribution (central sparing effect) and blood volume replacement from the placenta and extravascular space, with 40% of the hemorrhaged loss being corrected within 30 minutes.⁴⁸ The development of acidemia indicates that the fetus is not able to compensate; acidosis shifts the oxygen dissociation curve to the right, thereby decreasing fetal hemoglobin oxygen saturation but improving release of oxygen from hemoglobin. Blood flow during periods of asphyxia increases more than 100% to the brainstem, but only 60% to the cerebral hemispheres.⁴⁹

FETAL Oxygenation

The fetus exists in an environment of low oxygen tension, with arterial oxygen partial pressure (Po₂) being approximately one-fourth that of the adult. The maximum Po₂ of umbilical venous blood is approximately 30 mm Hg. The affinity of fetal hemoglobin for oxygen is modulated in utero by two principal factors: fetal hemoglobin and 2,3-diphosphoglycerate (2,3-DPG). The hemoglobin oxygen dissociation curve is shifted to the left because of fetal hemoglobin (hemoglobin F), thereby increasing the affinity for oxygen. 2,3-DPG is also present and might be expected to shift the oxyhemoglobin dissociation curve to the right, decreasing the affinity of the fetal hemoglobin for oxygen and favoring oxygen unloading. However, 2,3-DPG only appears to exert approximately 40% of the effect on fetal hemoglobin as it does on adult hemoglobin, thereby preserving a net leftward shift on the oxyhemoglobin dissociation curve. Thus for any given Po₂, the fetus has a greater affinity for oxygen than does the mother. The P50 (the Po₂ at which hemoglobin is 50% desaturated) is approximately 27 mm Hg for the adult and 20 mm Hg for the fetus. The concentration of 2,3-DPG increases with gestation, as does the concentration of hemoglobin A⁵⁰; the greater hemoglobin concentration (18 g/dL) results in a greater total oxygen carrying capacity.

Oxygen supply to fetal tissues depends on a number of factors (Table 37-1). First, the mother must be adequately oxygenated. Second, there must be adequate flow of well-oxygenated blood to the uteroplacental circulation. This blood flow may be reduced from maternal hemorrhage (reduced maternal blood volume) or compression of the inferior vena cava (reduced venous return), which increases uterine venous pressure, thus reducing uterine perfusion. Additionally, aortic compression reduces uterine arterial blood flow.⁵¹ Care must be taken to position the mother in such a way as to prevent aortocaval compression. The surgical incision of hysterotomy itself reduces uteroplacental blood flow by as much as 73% in sheep, whereas fetoscopic procedures with uterine entry have no effect.⁵²

TABLE 37-1 Causes of Impaired Blood Flow and Oxygenation to Fetal Tissues

IUGR, Intrauterine growth restriction; PET, preeclamptic toxemia.

Even if the uterine circulation is adequate, the fetus still depends on uteroplacental blood flow and umbilical venous blood flow for tissue oxygenation. Care must be taken not to interrupt umbilical vessel blood flow by manipulation or kinking the cord, which can cause vasospasm. Umbilical vasoconstriction can also occur as part of a fetal stress reaction resulting from a release of fetal stress hormones (Fig. 37-3). Increases in amniotic fluid volume increase amniotic pressure and impair uteroplacental perfusion.^53,54 Placental vascular resistance can be increased, raising fetal cardiac afterload, by the surge in fetal catecholamine production stimulated by surgical stress.⁵⁵ Fortunately, animal studies suggest that adverse effects on the arterial blood gas in the fetus do not occur until uteroplacental perfusion has been reduced by 50% or more.⁵⁶

FIGURE 37-3 Human fetal endocrine responses to stress. ACTH, Adrenocorticotropic hormone; CRH, corticotropin-releasing hormone; PoMc, proopiomelanocortin.

Inhalational anesthetics may cause maternal vasodilatation and, thus, in theory, could cause or exacerbate preexisting fetal hypoxia. Studies of anesthetics in hypoxic ovine fetuses have shown that isoflurane exacerbates preexisting acidosis.⁵⁷ It also causes blunting of the usual vascular redistribution response to fetal hypoxia, but, owing to a reduction in cerebral oxygen demand, the balance of cerebral oxygen supply and demand is unaffected. β-Adrenergic blockade renders a fetus less able to cope with asphyxia. Compared with controls, these fetuses have a smaller increase in heart rate, cerebral blood flow, and cardiac output, and recover from acidosis more slowly.⁵⁸

Central and Peripheral Nervous System Development

By the beginning of the second trimester, the spinal cord is largely formed; development of the brain and spinal cord begins as early as postconception week 3. Neural crest cells migrate laterally to form peripheral nerves from about 4 weeks, with the first synapses between them forming a week later.⁵⁹ Synapses within the spinal cord develop from about 8 weeks gestation, suggesting the first spinal reflexes may be present at this time. Between 8 and 18 weeks gestation is the time of maximal neuronal development. The first neurons and glial cells develop in the ventricular zone (an epithelial layer) along which the newly formed neurons migrate out in waves to form the neocortex. Synaptogenesis occurs after neural proliferation, first in peripheral structures and then more centrally from around 20 weeks; this process is at least partly dependent on sensory stimulation.⁶⁰

The development of the nociceptive apparatus proceeds in parallel with basic central nervous system development. The first essential requirement for nociception is the presence of sensory receptors, which develop first in the perioral area at around 7 weeks gestation. From here, they develop in the rest of the face and in the palmar surfaces of the hands and soles of the feet from about 11 weeks gestation. By 20 weeks, they are present throughout all of the skin and mucosal surfaces.⁶¹ The nociceptive apparatus is initially involved in local reflex movements at the spinal cord level without higher cortical integration. As these reflex responses become more complex, they, in turn, involve the brainstem, through which other responses, such as increases in heart rate and blood pressure, are mediated. However, such reflexes to noxious stimuli have not been shown to involve the cortex and, thus, are not thought to be available to conscious perception. The nature of fetal consciousness itself is complicated, both physiologically and philosophically, and a discussion of such is beyond the scope of this chapter. However, there is a working consensus that for consciousness to be present there must be electrical activity in the cerebral cortex.⁶² It appears that, far from being “switched on” at any one moment, consciousness evolves in a gradual process that has been likened to a “dimmer switch,” making attribution of fetal consciousness to any particular developmental moment a difficult undertaking.

Programming Effects

When considering the effects of noxious stimuli on the developing fetus and the rationale for fetal anesthesia and analgesia, we must consider not just the humanitarian need to alleviate the possible distress of pain sensation, but also whether being subjected to surgical stress during early development might cause permanent alterations in physiology. This concept is known as programming, defined as “the process whereby a stimulus or insult at a critical, sensitive period of development has permanent effects on structure, physiology, and metabolism.”⁶³ Studies in rats and nonhuman primates have shown permanent reductions in the numbers of hippocampal and hypothalamic glucocorticoid receptors in the offspring of antenatally stressed animals. This attenuates the negative feedback response, resulting in increased basal and stress-induced cortisol levels in the offspring, which last into adulthood. Behavioral changes, such as poor coping behaviors, have also been observed.⁶³

Use of FETAL Heart Rate Monitoring for FETAL Interventions

Currently, FHR monitoring with Doppler ultrasonography is the standard for the intrapartum assessment of fetal well-being. FHR monitoring is also used perioperatively during fetal interventions. The FHR is documented before maternal induction of anesthesia, to serve as a baseline for comparison and to reassure the perinatologist, surgeon, and anesthesiologist that the fetus is stable. The FHR may be continuously monitored intraoperatively by fetal echocardiography and with intermittent palpation of the umbilical cord in open cases. It is known that the most commonly used anesthetic induction agents at appropriate doses (propofol and thiopental) rapidly cross the placenta and thus also rapidly reach the fetus.^64,65 The inhalation anesthetics also cross the placenta,⁶⁶ but the uptake of the anesthetic occurs more slowly in the fetus than in the mother.^67,68 These anesthetics decrease FHR and FHR variability. Although it is reassuring if the FHR is within the normal range for the gestational age, fetal bradycardia is a reliable indicator of fetal distress that needs to be immediately addressed.

With the advent of minimally invasive fetal endoscopic surgery, new problems in monitoring have surfaced. The fetus is no longer physically accessible to the surgical team, and the trocars used for fetoscopic surgery currently prohibit the placement of radiotelemetric probes. At present, fetoscopic or cardiac intervention use direct visualization of the heart with fetal echocardiography, which gives an accurate estimation of the FHR. Although very beneficial, the continuous use of fetal echocardiography requires the presence of a skilled ultrasonographer working in the operative field.

Use of FETAL Blood Sampling during FETAL Interventions

In suspected cases of fetal compromise during an open intervention, fetal blood can be obtained from capillary vessels, a peripheral vein, a central vein, or a puncture of the umbilical vessels. The fetus’ small size and friable tissue make vascular access difficult. Puncture of the umbilical vessels can lead to cord spasm, hematoma, and even fetal death, and thus should be reserved for circumstances when no other options are available. During an endoscopic intervention, access to the fetal circulation is possible through puncture of the umbilical vessels. With most fetal cardiac interventions, a needle and/or catheter is placed directly through the fetal myocardium, allowing access for blood samples; only a very small sample should be withdrawn because of the small circulating fetal blood volume.

FETAL Electrocardiography

Several groups have used fetal ECG analysis to determine whether changes in time interval (PR and RR interval) and signal morphology (T to QRS ratio) correlate with fetal or neonatal outcome. Studies in animals and humans have shown that under normal conditions, there is a negative correlation between the PR interval and the FHR: as the FHR slows, the PR interval lengthens, and as the FHR increases, the PR interval shortens. The opposite relationship occurs in acidemic infants.^69–75 During periods of fetal compromise, it is hypothesized that the sinoatrial node and the atrioventricular node respond differently.⁷³ Periods of mild hypoxemia will induce increases in epinephrine levels, which will increase the FHR and shorten the PR interval. However, with periods of prolonged hypoxemia, the oxygen-dependent calcium channels of the sinoatrial node will demonstrate reduced sensitivity to epinephrine, resulting in a decrease in FHR. The fast sodium channels of the atrioventricular node are not affected by the reduction in the oxygen supply, and the increased levels of epinephrine will shorten the PR interval. As a result, the relationship between the PR interval and FHR changes from negative to positive.⁷³ Measurements of this relationship have been divided into short-term and long-term measures.^73,74 The short-term measure or the conduction index can be intermittently positive over short periods of time without an adverse outcome. However, a prolonged positive conduction index (greater than 20 minutes) has been associated with an increased risk of fetal acidemia.⁷⁵

FETAL Pulse Oximetry

Standard pulse oximeters use the transmission and absorption of light through a vascular bed to a photodetector on the opposite side of the tissue. However, the development of reflectance oximetry allowed measurement of oxygen saturation from light-emitting diodes that are positioned next to each other on the same skin surface and absorption is determined from the light that scatters back to the tissue surface^76,77; any fetal condition that decreases vascular pulsations (e.g., hypotension, vasoconstriction, shock, or strong uterine contractions) can produce inaccurate oximetry readings.⁷⁸ Because direct contact of the oximeter must be made with the fetal skin surface, anything that interferes with light transmission or skin adhesion (e.g., fetal or maternal movement, vernix caseosa, caput succedaneum) can influence the quality and accuracy of the oximeter.^79–83 Oximetry readings also vary in relation to the site of sensor application; several studies have found reduced baseline oxygen saturation values with the use of the oxygen sensor on the fetal buttock compared with the fetal head.^84–87

The development of a 735/890-nm wavelength system (compared with the older 660/890-nm system) has improved the accuracy in monitoring arterial oxygen saturation (FSao₂) in the fetus⁸⁸; because the normal range of FSao₂ of 30% to 70% lies in the middle of the oxygen-hemoglobin dissociation curve, small changes in pH or oxygen partial pressure cause large changes in FSao₂.⁸⁹ FPO can also identify an acidotic fetus. Increased concentrations of both the hydrogen ion and 2,3-DPG cause a rightward shift of the oxygen dissociation curve (Bohr effect) such that a chronically acidemic or hypoxemic fetus will have a low FSao₂ even though the Po₂ is within normal limits.⁸⁹

FETAL Echocardiography

When technically feasible, fetal echocardiography should be available to assess fetal myocardial contractility and function, heart rate, intravascular volume status, and amniotic fluid volume. We have also used echocardiography to correctly identify proper endotracheal tube placement during an EXIT procedure⁹⁰; a sterile sleeve is placed over the ultrasonographic probe that is then placed over the fetal chest.

Doppler Ultrasonography of FETAL Cerebral Blood Flow

Antepartum Doppler ultrasonography studies of the fetal circulation in cases of intrauterine growth restriction with presumed hypoxia have shown a compensatory redistribution, with an increase in peripheral vascular resistance in the fetal body and placenta and a compensatory reduction in peripheral vascular resistance in the fetal brain, producing a brain-sparing effect.⁹¹ Intrapartum Doppler ultrasonography and FPO have verified the brain-sparing response in the presence of intrapartum arterial hypoxemia (FSao₂ less than 30% for 5 minutes or more), as reflected by increased mean flow velocity in the fetal middle cerebral artery.⁹² Preliminary studies of the middle cerebral artery pulsatility index in minimally invasive procedures, such as fetal blood sampling, transfusion, shunt insertion, tissue biopsy, and ovarian cyst aspiration, have demonstrated significant cerebral hemodynamic responses (decreases in the middle cerebral artery pulsatility index) in fetuses that underwent procedures involving transgression of the fetal body. This response was not noted in the fetuses undergoing procedures at the noninnervated placental cord insertion.⁹³

Although not yet advocated for routine intrapartum management, it has been suggested that the combination of reduced arterial oxygen saturation and increased cerebral blood flow may indicate an ominous phase during labor. The redistribution of the fetal circulation is not an unlimited protective mechanism, and with persistent cerebral hypoxia, the active vasodilation of the cerebral vessels may fail, leading to disastrous consequences for the fetus.⁹⁴

Respiratory and Airway Considerations

There is an increase in metabolic demand of both the mother and the fetus, and this, along with anatomic and hormonal influences, accounts for the changes in maternal pulmonary physiology (Table 37-2). Pregnancy results in progressive increases in oxygen consumption and minute ventilation, along with a decreased residual volume and functional residual capacity.⁹⁵ The increased metabolic demands and anatomic changes can make adequate oxygenation and perfusion of the parturient and the fetoplacental unit a constant challenge during maternal general anesthesia. During periods of apnea or hypoventilation, the parturient is prone to rapid development of hypoxia and hypercapnia. Even after adequate preoxygenation, the Pao₂ in an apneic anesthetized parturient decreases by about 8 mm Hg more per minute than in nonpregnant women.⁹⁶ Acidosis rapidly develops from hypoxia during difficult airway situations because of a decreased buffering capacity during pregnancy. The decreased pulmonary oxygen stores and increased oxygen consumption make parturients more susceptible than nonpregnant women to the consequences of airway mismanagement.

TABLE 37-2 Anesthetic Considerations of Respiratory Changes of Pregnancy

Petco₂, End-tidal carbon dioxide pressure.

Not all physiologic changes of pregnancy are deleterious to the performance of anesthesia. For example, both the induction of and emergence from anesthesia with inhalational anesthetics occur faster in parturients than in nonpregnant women because the combination of increased alveolar ventilation and decreased functional residual capacity speeds the rate at which denitrogenation occurs and at which inspired and alveolar concentrations of inhalational agents reach equilibrium⁹⁷; a faster induction, coupled with a decreased MAC, make parturients susceptible to relative anesthetic overdose and severe hypotension.⁹⁸

Cardiovascular Considerations

Cardiovascular function is appropriately increased during pregnancy to meet the increased metabolic demands and oxygen requirements of the mother (Table 37-3). Cardiac output increases by 35% to 40% by the end of the first trimester and continues to increase throughout the second trimester until it reaches a level 50% greater than that in nonpregnant women.⁹⁹ Heart rate increases 15% to 25% above prepregnancy rates and remains stable after the second trimester, and stroke volume progressively increases 25% to 30% by the end of the second trimester and remains stable until term.^100,101 Aortocaval compression by the gravid uterus can cause a 30% to 50% decrease in cardiac output; lesser decreases occur in the sitting or semirecumbent positions. Maternal position is a major factor contributing to hypotension and fetal well-being.¹⁰²

TABLE 37-3 Anesthetic Considerations of Cardiovascular Changes of Pregnancy

Maternal blood flow and pressure are directly linked to fetal perfusion via the placenta, and uterine blood flow represents about 10% of maternal cardiac output. The avoidance of aortocaval compression by left or right uterine displacement is imperative to prevent a decrease in the maternal blood pressure. Because large doses of inhalational agent are often necessary for uterine relaxation during fetal intervention, prompt treatment of hypotension is vital. Because uteroplacental blood flow is not autoregulated, a decrease in maternal blood pressure will eventually decrease placental blood flow and, therefore, blood flow to the fetus. IV ephedrine (5 to 10 mg) or phenylephrine (50 to 100 µg) per dose should be used to treat maternal hypotension unless contraindicated.¹⁰³

Careful attention to the volume status of the parturient is imperative; aggressive volume hydration, the normal decrease in colloid oncotic pressure that occurs during pregnancy, the decrease in colloid oncotic pressure post partum, and the use of tocolytic agents (e.g., magnesium or β-adrenoceptor agonists) may all predispose the parturient to pulmonary edema.

Central and Peripheral Nervous Systems

Pregnancy-mediated analgesia is affected by changes in spinal opioid antinociceptive pathways and peripheral processes, including the effect of ovarian sex steroids (estrogen and progesterone) and uterine afferent neurotransmission. It is thought that pregnancy-mediated analgesia increases the woman’s threshold for pain during the latter stages of pregnancy before labor.^104,105 Pregnant women are more sensitive to the action of many anesthetic agents and require less local anesthetic for spinal and epidural anesthesia and less inhalational anesthetics than their nonpregnant counterparts. The MAC of inhalational anesthetics in pregnancy is approximately 30% less than in nonpregnant females; and for this reason the concentration of inhalational anesthetic needs to be carefully titrated.¹⁰⁶

Pharmacologic Consequences of Pregnancy

Physiologic changes of pregnancy alter the pharmacokinetics and pharmacodynamics of many anesthetic drugs. An increase in total body water and adipose tissue, and a decrease in plasma protein concentrations alter the volume of distribution. An increased renal blood flow and glomerular filtration rate can enhance the elimination of renally excreted drugs; hepatic metabolism of some drugs may be inhibited by competition with steroid hormones during pregnancy, whereas others may have a greater clearance associated with the increased basal metabolic rate. Therefore drug administration must consider the pharmacokinetics within the maternal-placental-fetal unit. Most drugs cross the placenta to some extent and the proportion transferred increases with the duration of gestation. The fetus has reduced plasma protein binding, producing relatively greater concentrations of free drug (i.e., unbound and available to cross biologic membranes).¹⁰⁷ Despite detection of oxidation and reduction reactions in the fetal liver from as early as 16 weeks, enzyme concentrations and reaction rates are minimal, exposing the fetus to more prolonged drug effects than occur in the mother.¹⁰⁸ Early in gestation, the primary mode of drug excretion is via blood flow to the placenta, but later, as the fetal kidneys mature, they become a route of drug excretion into the amniotic fluid for water-soluble drugs and metabolites. Amniotic fluid, however, can act as a reservoir for drugs, from which they can be reabsorbed.¹⁰⁷

Hormonal Receptors in Labor

The adrenergic hormonal system plays a very influential part in the activity of the myometrium; several types of adrenergic receptors are found in the uterus (Fig. 37-4). Stimulation of the α-adrenergic receptor causes an increase in the rate and intensity of uterine contractions, whereas activation of the β₂-adrenergic receptors produce myometrial relaxation.¹²⁹ In addition, the term uterus is heavily populated with receptors for endogenously released oxytocin responsible for initiating uterine contractions. Prostaglandins also play a significant role in modulating myometrial tone. In general, prostaglandins are produced in or near the local environment where they exert their effect; both uterotonic and tocolytic prostaglandins have been identified. The balance of intrauterine and maternal uterotonic prostaglandins is thought to play an essential part in the preparation for both term and preterm labor. Prostaglandins, especially prostaglandin E₂, are an essential component of every aspect of natural labor.¹³⁰

FIGURE 37-4 Biochemistry of uterine contraction and its inhibition. AC, Adenylate cyclase; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; Gc, G-protein c; Gs, G-protein s; IP3, inositol triphosphate; MLCK, myosin light-chain kinase; PI, phosphatidylinositol; SR, sarcoplasmic reticulum.

Treatment of Acute Preterm Labor

Pain Control

Pain control after fetal surgery is an essential component of tocolytic therapy, because it is thought that adequate pain control prevents the stress-induced hormonal impetus for preterm labor. Surgical stress elicits the release of adrenocorticotropic hormone that increases production of cortisol; cortisol production, in turn, leads to the deleterious changes in the placenta that increase fetal estrogen and prostaglandin production, promoting increased uterine activity.

FETAL Complications of Tocolytic Therapy

The adverse effects of tocolytics in the fetus present a number of problems, albeit usually less so than in the mother. Sympathomimetics that act through β-adrenoceptors cause fetal tachycardia.¹³⁷ Whereas cyclooxygenase inhibitors have been shown to be more effective than other tocolytics in delaying labor,¹³⁸ the adverse effects of fetal oliguria and ductus arteriosus constriction have limited their long-term use.¹³⁹ However, after short-term use, these adverse effects are fully reversible within 72 hours from cessation of treatment.¹³⁹ Longer-term use of indomethacin has been associated with renal dysfunction and increased rates of necrotizing enterocolitis, intracranial hemorrhage, and patent ductus arteriosus in infants delivered at less than 30 weeks gestation.¹⁴⁰ Magnesium sulfate reduces FHR variability¹⁴¹ and depresses fetal right ventricular function.¹⁴² Because this drug rapidly crosses the placenta but is excreted more slowly by the fetal kidneys than by the maternal kidneys, there are concerns about fetal toxicity, resulting in respiratory and central nervous system depression.¹⁴³ Nitric oxide donors, such as nitroglycerin, appear to have minimal fetal side effects.¹⁴⁴

Postoperative Pulmonary Edema

Noncardiogenic pulmonary edema is a known complication of tocolysis. Most often, obstetric pulmonary edema is a result of increased hydrostatic pressures and resolves rapidly with diuretics, cessation of tocolytics, and fluid restriction. One study observed a prevalence of pulmonary edema of 0.5%, but that rate increased to 23% in fetal surgical patients; 93% of those with pulmonary edema required intensive care and 20% required tracheal intubation.¹³⁴ It has been hypothesized that extensive uterine manipulation during surgery may result in release of mediators that increase the permeability of lung vasculature. The class of medications most strongly associated with pulmonary edema is β-adrenergic–mimetic agents. An additional important observation is that patients receiving nitroglycerin for tocolysis have demonstrated more pronounced pulmonary edema (more severe hypoxemia, greater time to resolution, worse chest radiograph, and a greater composite lung injury scores) than those who received other tocolytics.¹³⁴

Congenital Cystic Adenomatoid Malformation of the Lung

CCAM of the lung consists of cystic masses of pulmonary tissue and bronchial structures, neither of which participate in gas exchange,^150,151 that may represent a form of pulmonary hypoplasia.¹⁵² CCAMs can compress surrounding lung tissue and impede normal lung development, resulting in pulmonary hypoplasia.¹⁵³ Of all the fetal lung masses, CCAM is the lesion most frequently associated with hydrops fetalis that often indicates a premorbid fetal state. Although the exact mechanisms for the development of hydrops are unclear, it has been suggested that it is secondary to either cardiac compression or vena caval obstruction from the intrathoracic mass.^154,155 This condition is associated with a significant imbalance of fetal fluid, resulting in accumulation of fetal fluid causing increases in fetal interstitial and total body water, pericardial and pleural effusions, ascites, anasarca, polyhydramnios, or placental thickening.^156,157

Fetal lung abnormalities themselves may lead to excessive fluid accumulation because the fetal lung is an important organ for amniotic fluid balance. The average fetal lung fluid production is estimated to be approximately 300 mL/day or about 4 mL/kg/hr.¹⁵⁸ Fetal urine output is approximately 700 mL/day, and fetal swallowing is about 700 mL/day. The remaining 300 mL/day is postulated to exit the amnion through the chorioamnionic membrane. CCAMs may impair fetal swallowing via esophageal obstruction and therefore disrupt normal fluid balance; fetal swallowing is the major method by which amniotic fluid water is returned to the fetal vascular compartment. A second possibility is hypersecretion or transudation of fluid from the CCAM itself.

Intervention

The fetal hemithorax and upper extremity are delivered through the hysterotomy. Warm fluids are continuously infused into the uterine cavity from a high-volume fluid warmer to replace amniotic fluid losses, provide a thermoneutral environment for the fetus, and prevent umbilical cord kinking or stretching. Limiting the size of the uterine incision helps prevent fetal evaporative fluid loss, uterine hemorrhage, and postoperative uterine contractions. Once the fetal hemithorax and upper extremity have been delivered into the operative field, fentanyl (5 to 20 µg/kg), atropine (20 µg/kg), and an NMBD (usually vecuronium 0.2 mg/kg or pancuronium 0.1 mg/kg) are given IM as a single injection into the exposed shoulder of the fetus.¹⁶⁰ Fentanyl is administered for intraoperative and postoperative fetal analgesia and to suppress the fetal stress response, atropine ablates the expected bradycardic response with fetal surgical manipulation, and an NMBD will ensure an immobile fetus during surgery. Although the fetus receives anesthesia from transplacental transfer of maternal inhaled anesthetic, these additional IM medications augment fetal anesthesia and ensure fetal analgesia before thoracotomy.

A pulse oximetry probe can be applied to the exposed fetal extremity. Fetal echocardiography provides information about FHR and ventricular filling, which is particularly useful in those procedures in which fetal blood loss is anticipated (Fig. 37-6). Fetal lung lesions, especially if composed of multiple tissue types, may have a very irregular vascular supply, and significant fetal hemorrhage is possible. Direct vascular access in the exposed upper extremity allows immediate resuscitation and blood administration as needed. Even surgical manipulations alone can lead to hemodynamic instability, requiring urgent resuscitation. This may be secondary to mediastinal torsion, resulting in a sudden loss of cardiac preload.

FIGURE 37-6 In-utero thoracotomy in a 22-week fetus after excision of congenital cystic adenomatoid malformation.

(Courtesy N. Scott Adzick, MD, Children’s Hospital of Philadelphia.)

Closure

Once the lung lesion has been resected and fetal well-being is confirmed, the fetus is returned to the intrauterine environment and the hysterotomy incision closed. Closure consists of two separate layers, thus minimizing the risk for postoperative amniotic fluid leak and uterine wall dehiscence (Fig. 37-7). It is important to maintain complete uterine relaxation during closure, because uterine manipulation can alter blood flow and place the fetus at risk of hypoperfusion. Before the last uterine stitches, intraamniotic volume is assessed via ultrasonography and any deficit is replaced with warmed Ringer’s lactate solution.

FIGURE 37-7 Hysterotomy closure.

(Courtesy N. Scott Adzick, MD, Children’s Hospital of Philadelphia.)

Once the uterine incision is closed, the surgeon begins to close the maternal abdominal wall. At this time, a loading dose of magnesium sulfate (6 g) is administered IV over 20 minutes, followed by a 3-g/hr infusion that is continued postoperatively. The epidural catheter can be dosed with local anesthetic (15 to 20 mL of 0.25% bupivacaine) and an opioid (e.g., fentanyl 1 to 2 µg/kg) as the inhalational anesthetic is decreased or discontinued. Careful attention to the degree of neuromuscular blockade is needed, as magnesium sulfate potentiates the action of the muscle relaxants. Extubation occurs as soon as the usual criteria for extubation are met.

Pulmonary Sequestration

Pulmonary sequestration, also known as bronchopulmonary sequestration, accessory lung, or bronchopulmonary foregut malformation, represents 0.5% to 6% of congenital lung disease (0.15% and 1.7% of live births).^30–32 Pulmonary sequestrations consist of nonfunctional lung tissue that does not communicate with the normal tracheobronchial tree and hence does not participate in gas exchange.³¹ Pulmonary sequestration may be differentiated from CCAM by investigation of its blood supply. Unlike pulmonary sequestrations, CCAMs derive their blood supply and venous drainage from the pulmonary circulation. A multitude of somatic anomalies have been associated with sequestration, most commonly diaphragmatic hernia. If not treated in utero, these lesions often present as respiratory distress in the neonatal period or as chronic respiratory infections in older children.

Bronchogenic Cysts and Mixed or Hybrid Pulmonary Lesions

Bronchogenic cysts are embryonic abnormalities considered to be a type of bronchopulmonary foregut malformation.¹⁷⁷ These cysts are thought to result from an abnormal budding of the primitive bronchial tree between weeks 4 and 8 of gestation, thus representing abnormal lung development at an early stage of ontogeny.¹⁷⁸ In most cases, bronchogenic cysts are asymptomatic in the first months of life. A notable exception is a mediastinal cyst that usually manifests as stridor.

Although in-utero complications are less likely than with the other fetal lung lesions previously described, the propensity of these lesions to cause life-threatening postnatal complications warrants close attention throughout the prenatal period. Fetal intervention with intermittent or continuous drainage of cysts can prevent the secondary morbidity; definitive fetal surgery with thoracotomy has also been successful.¹⁷⁹

Sacrococcygeal Teratoma

Sacrococcygeal teratomas (SCTs, Fig. 37-8) are one of the most common congenital neonatal tumors (1 per 40,000 live births).^180–182 A variety of tissues from the three primary germ layers are usually found, and the size of the tumor is quite variable.^183,184 Most SCTs are external, usually protruding from the perineal region. The majority include both solid and cystic components, with only 15% being entirely cystic.^185,186 Although usually benign, SCTs can cause significant secondary morbidity in selected cases because of the tumor’s mass effect and vast blood supply.¹⁸⁷ With smaller tumors, complete surgical resection usually occurs after delivery under elective, controlled conditions. In extreme cases, the tumor can cause fetal congestive heart failure (usually high output failure), and even fetal demise if no treatment is performed.¹⁸⁸ Death is usually secondary to an enlarged tumor mass and associated polyhydramnios, resulting in preterm labor and delivery, with ultimate survival dependent on fetal lung maturity. Massive hemorrhage into the tumor with fetal exsanguination may occur spontaneously in utero or be precipitated by labor and delivery. Prenatal intervention may be necessary, including intrauterine transfusion or fetal surgery for those fetuses that develop significant secondary morbidity (e.g., hydrops).

FIGURE 37-8 Fetal sacrococcygeal teratoma before in-utero resection in a 22-week fetus.

(Courtesy N. Scott Adzick, MD, Children’s Hospital of Philadelphia.)

Rationale for FETAL Cardiac Intervention

Most CHDs can be safely repaired in infancy, with excellent surgical survival and long-term prognosis. For these defects, there would be no need for in-utero intervention; and for many defects, in-utero intervention would not be technically possible (e.g., arterial switch procedure for transposition of the great arteries). For other defects, surgical correction itself may not be possible and the only option is staged surgical palliation, which is often associated with significant surgical morbidity and mortality.^189,194,195 As such, the risk of performing any fetal intervention must be balanced against the potential benefits of improving the anticipated outcome of surgery performed in the neonatal period to correct the specific cardiac defect. It is the intention of prenatal intervention for certain types of CHD to reverse the pathologic process in an attempt to preserve cardiac structure and function and, thus, it is hoped, prevent serious postnatal disease. A secondary aim of prenatal intervention is to modify the severity of the disease and improve postnatal surgical outcomes.

Defects Amenable to in-Utero Repair

Certain congenital heart defects cause aberrations in blood flow, which are usually secondary to valvular stenosis or regurgitation. Regardless of the etiology, the end result is often an abnormally developed ventricle.¹⁹⁶ Several case reports have characterized the progression of valvular stenosis to ventricular hypoplasia from reduced flow through the chamber during gestation.^197–199 It has been hypothesized that relief of valvular stenosis in utero could reverse the progression toward ventricular hypoplasia. In these cases, there may be a window of opportunity in which ventricular growth can be salvaged. Because most routine prenatal ultrasonographic screening is performed between 16 and 24 weeks gestation, the window of opportunity for prenatal intervention is likely between 20 and 26 weeks gestation.

To date, the defect most amenable to correction is severe aortic stenosis with evolving HLHS.^197–200 Without prenatal intervention, severe aortic stenosis can lead to marked left ventricular dysfunction, diminished flow through the left heart, arrest of left ventricular growth, ventricular fibroelastosis, and, consequently, HLHS. Aortic valve dilation may be performed percutaneously with ultrasound guidance. Optimal fetal positioning, placental location, or maternal habitus may require exposure of the uterus through an abdominal incision to obtain ideal access to the fetal thorax. These procedures have been performed under both maternal regional and general anesthesia, although general anesthesia is often preferred to obtain optimal uterine relaxation and an anesthetized fetus. Preliminary results are promising, but larger prospective investigations are warranted to determine long-term outcomes.²⁰¹

Technical Aspects of FETAL Cardiac Interventions

Open cardiac surgery on the fetus is not presently technically possible.^202–206 In humans, all of the reported procedures to date have been attempted using the transcutaneous or transuterine approach with ultrasound-guided access into the fetal heart.^191–193 Although hysterotomy would provide means for more direct fetal access (e.g., femoral artery, transumbilical or carotid artery access), maternal morbidity would be significantly increased and postoperative premature labor certain. After valvuloplasty, the fetus requires time for the ventricle to recover. Therefore, any procedure that substantially increases the likelihood of early delivery would likely be counterproductive.

Although initial percutaneous techniques for fetal cardiac valvuloplasty were performed with only the mother receiving sedation,^191,192 recent advances in surgical techniques have led to provision of maternal and fetal analgesia and anesthesia.²⁰⁷ The mother usually receives general anesthesia. After ultrasonographic confirmation of placental location, the maternal abdomen and uterus are punctured with a 22-gauge spinal needle. An IM injection of fentanyl, atropine, and a muscle relaxant is delivered to the fetus. A 19-gauge needle is subsequently directed into the fetal thorax, and access to the fetal heart is obtained. A small coronary balloon-tipped catheter is threaded over a guidewire through the needle, and passed through the stenotic valve or closed septum. The catheter balloon is then dilated, and blood flow is confirmed using Doppler ultrasonography (Fig. 37-9). The technique has been modified in certain cases, such that a laparotomy to expose the uterus is performed. Using this technique, better ultrasonography and ideal fetal positioning are possible to achieve optimal access to the fetal thorax.

FIGURE 37-9 Technique for balloon dilation of a stenotic aortic valve in a fetus with hypoplastic left heart syndrome.

(Reproduced with permission from Dream Magazine, Spring/Summer 2002, Boston: Children’s Hospital Boston; 2002. p. 20.)

Anesthetic Management for the Mother

Most cases of fetal cardiac intervention are performed using a percutaneous technique or through a laparotomy incision with direct uterine exposure. The surgical approach will vary according to patient habitus, placental position (anterior vs. posterior), and fetal position. For the less invasive percutaneous approach, the choice of a regional anesthetic accompanied by IV sedation for the mother may be acceptable. However, it must be remembered that although the placental transfer of sedative drugs administered to the mother may sedate the fetus, an anesthetized or immobile fetus is not guaranteed. Excessive fetal movement makes most cardiac interventions impossible and even dangerous to both the fetus and mother.

Patients who received an epidural anesthetic technique required significantly more IV fluids but less IV opioid. The administration of large amounts of crystalloid and tocolytics during fetal surgery increases the risk of maternal pulmonary edema.^208,209 Neuraxial techniques (e.g., spinal, epidural, and combined spinal-epidural anesthesia) have been used in other percutaneous and fetoscopic procedures; a T4 sensory level blockade is required. It should be noted that neuraxial anesthesia provides no uterine relaxation and no analgesia or anesthesia to the fetus unless supplemented with IV maternal analgesics and sedatives (e.g., fentanyl, benzodiazepines, propofol). Because of these issues, it is generally recommended, even in anticipated percutaneous procedures, to deliver a general anesthetic to the mother. If there is a high suspicion of a laparotomy being performed, a dose of spinal Duramorph (morphine sulfate) may be delivered to the mother before the anesthetic induction for postoperative pain relief and resultant suppression of myometrial contractility after laparotomy.^197,198

Anesthetic Management for the Fetus

Anesthesia for percutaneous and fetoscopic interventions, of which fetal cardiac interventions are a significant subset, pose several unique challenges for the anesthesiologist. The combination of immature organ systems and the underlying cardiac anomaly places the fetus at considerable anesthetic risk. Unlike adults and older children, fetal cardiac output depends more on heart rate than on stroke volume. Because fetal myocardial contractility is likely maximally stimulated, the fetus has a limited ability to increase stroke volume. Therefore, it is plausible that fetal patients with congenital heart disease and evidence of failure (i.e., hydrops) will exhibit more pronounced physiologic limitations. Notably, anesthetic-induced decreases in contractility, combined with intracardiac catheter manipulation in a structurally compromised heart, can result in fetal hypotension, bradycardia, and eventual cardiac collapse and death. It is generally accepted that neonates manifest a greater degree of hypotension in response to isoflurane and halothane at equipotent anesthetic concentrations when compared with older children.^210,211

Because direct exposure of the fetus is not warranted during most cardiac interventions, intraoperative monitoring is limited to echocardiography. An ultrasonographer continually monitors the fetal heart during placement of the intracardiac needle and during catheter balloon inflation. A continuous echocardiogram is also useful for measuring FHR, contractility, and volume status.

Intraoperative FETAL Resuscitation during Percutaneous Interventions

If fetal bradycardia (heart rate less than 100 beats per minute) or significantly reduced ventricular function develops, resuscitation proceeds immediately. Because direct vascular access to the fetus may not be immediately available, several other treatments can be employed. Intracardiac and IM administration of epinephrine (1 to 2 µg/kg) may be used to treat severe sustained bradycardia. Other maneuvers improve uterine perfusion and hence fetal oxygenation and include increasing maternal mean arterial pressure to 15% to 25% above awake values with volume loading and ephedrine or phenylephrine, and decreasing uterine vascular resistance by ensuring adequate uterine relaxation. Occasionally, pericardial tamponade may cause impaired cardiac function; needle drainage of the effusion may be necessary for fetal survival. If fetal echocardiography indicates a decreased ventricular volume, an intracardiac blood transfusion with O-negative irradiated blood (5 to 10 mL/kg) may be indicated.

Postoperative Considerations

The fetus is monitored postoperatively with intermittent ultrasonographic examinations. The incidence of premature contractions and labor is less after fetoscopic surgery than after open hysterotomy.^212,213 Fetoscopic intervention also appears to have reduced requirements for tocolysis and a reduced rate of premature delivery.²¹³ If early delivery should occur, many of these fetuses are considered nonviable owing to their young gestational age (usually less than 24 weeks gestation) and serious cardiac disease.

TWIN–TWIN Transfusion Syndrome

Twin–twin transfusion syndrome (TTTS) is a serious complication occurring in 10% to 15% of monozygotic monochorionic twin pregnancies.²¹⁴ Although all monochorionic twin pregnancies demonstrate one or more placental vascular anastomoses, TTTS represents a pathologic form of circulatory imbalance between the monochorionic twin fetuses.²¹⁵ As a result of this imbalance, a net fetofetal transfusion occurs, from one twin (the donor) to the other (the recipient) (Fig. 37-10). Symptoms develop rapidly and, in the donor twin, include hypovolemia, oliguria, oligohydramnios, and growth retardation. In turn, the recipient twin develops hypervolemia, polyuria, polyhydramnios, and signs of circulatory volume overload, resulting in congestive heart failure.^214–218 In severe cases, if untreated, TTTS may result in intrauterine fetal death and miscarriage. Even if twins with TTTS survive, there remains a high incidence of secondary neurologic and pulmonary morbidities.

FIGURE 37-10 Schematic representation of umbilical cord ligation in twin reversed arterial perfusion sequence.

(Courtesy T.M. Crombleholme, MD.)

Fetoscopic laser photocoagulation of the communicating vessels associated with TTTS is based on three fundamental assumptions: (1) the syndrome occurs in the presence of vascular communications between fetuses in a monochorionic gestation, (2) obliteration of these vessels can halt the pathophysiologic process, and (3) both deep and superficial communications can be interrupted at the surface of the placenta.²¹⁹ Fetoscopic laser surgical occlusion of superficial communicating vessels is associated with a reported survival rate of 55% to 83% and a reduced neurologic complication rate (5%) among survivors.^214,216

There are few data on the reported anesthetic techniques used for fetoscopic laser ablation. The procedure has been performed with local, general, epidural, and combined general and epidural anesthesia.^220–223 Factors that may influence the anesthetic technique include (1) the planned surgical approach and probability of converting to open fetal surgery; (2) the likelihood of surgical perturbation of innervated fetal tissues; (3) maternal preference; and (4) a history of prior uterine activity. The surgical approach for fetoscopic laser photocoagulation is determined by (1) the location of the placenta (anterior vs. posterior), (2) the position of the fetuses, and (3) the potential window(s) for trocar insertion.²²⁴

Twin Reversed Arterial Perfusion Sequence

Twin reversed arterial perfusion (TRAP) sequence denotes a common pathophysiology of several different conditions, all of which describe a twin pregnancy in which one twin is normal and the second twin exhibits multisystem malformations, including anencephaly or acardia. The twin with the hemodynamic advantage is denoted as the “pump” twin, perfusing deoxygenated blood in a retrograde direction to the other twin, “the recipient twin.” The term reversed perfusion is used to describe this scenario because blood enters the acardiac or anencephalic twin through its umbilical artery and exits through the umbilical vein. This eventually places the normal or “pump” twin at a hemodynamic disadvantage because this normal twin provides cardiac output to both itself and the nonviable sibling. This anomaly places the pump twin at risk of cardiac overload and congestive heart failure, often with associated hepatosplenomegaly.

Perinatal complications with TRAP sequence range in severity, with reported death rates for the pump twin ranging from 39% to 59% in untreated pregnancies.²²⁵ Treatment options include observation, medical therapy with digoxin and indomethacin, selective delivery, umbilical cord blockade with a coil, and fetoscopic cord ligation. Although all endoscopic procedures have the primary aim of interrupting umbilical cord blood flow to the nonviable twin, this invasive technique is generally employed after failed medical therapy or after signs of cardiac failure in the viable twin.^226,227

Needle Aspiration and Placement of Shunts

A variety of fetal disorders may benefit from in-utero needle aspiration or shunt placement. These disorders include posterior urethral valves, aqueductal stenosis, fetal hydrothorax, ovarian cyst, and fetal ascites. Various shunts have been attempted to provide long-term decompression, with variable results.²²¹

FETAL Diseases Eligible for the EXIT Procedure

Cervical Teratoma

Cervical teratomas are rare (1 per 20,000 to 40,000 live births) and can extend from the mastoid process to the sternal notch inferiorly and to the trapezius muscle posteriorly. They can also invade the oral floor and extend into the anterior mediastinum. Many of the larger teratomas diagnosed prenatally cause maternal polyhydramnios, which is secondary to esophageal compression by the tumor and impaired fetal swallowing. Most of these tumors are benign but are associated with substantial mortality rates caused by airway compression and difficulty in establishing an adequate airway after delivery (Fig. 37-12).²³¹ Of neonates with cervical teratomas, 30% die of airway obstruction shortly after delivery²³²; for infants not diagnosed prenatally, mortality rates are even greater.^233,234 In addition, some larger tumors may interfere with normal delivery methods and necessitate emergent alterations in maternal care, placing the mother at increased risk.^231,235

FIGURE 37-12 Newborn with a massive oropharyngeal cervical teratoma immediately after ex utero intrapartum treatment was performed to secure the airway. Immediate resection of the teratoma followed in an adjacent operating room.

Until recently, treatment options for infants with cervical teratomas who survived the intrauterine period were limited. The standard of care incorporated scheduled cesarean section followed by various airway maneuvers, including the establishment of a surgical airway. Even with skilled help immediately available, dismal outcomes were common.^231–233 Despite securing the airway, critical time is needed to perform this task, often at the expense of neonatal oxygenation. With the introduction of the EXIT procedure, precious time is provided to locate the trachea and provide a definitive airway before clamping the umbilical cord, thereby maintaining continuous fetal oxygenation and decreasing morbidity and mortality.

Cystic Hygroma

Cystic hygromas arise from the failure of the jugular lymph sacs to join the lymphatic system early in fetal development, resulting in the development of endothelium-lined cystic spaces that eventually compress normal surrounding structures. This compression may result in fetal hydrops, including skin edema, ascites, and pleural or pericardial effusions (Fig. 37-13).^233,234 In infants with isolated cervical cystic hygroma and no evidence of hydrops, airway compromise at birth or shortly thereafter is the main therapeutic concern. These infants are considered candidates for EXIT procedures.

FIGURE 37-13 Fetus (with a cystic hygroma) that underwent ex utero intrapartum treatment to establish a surgical airway before delivery.

(Courtesy N. Scott Adzick, MD, Children’s Hospital of Philadelphia.)

EXIT to ECMO

In addition to airway management, the EXIT procedure may be considered for other instances in which separation from uteroplacental support is expected to cause critical cardiac or pulmonary compromise. Fetuses with congenital heart disease who are expected to need emergent ECMO at birth and fetuses with poor-prognosis congenital diaphragmatic hernias may benefit from the “EXIT to ECMO” strategy.^230,242 Neonates undergoing this procedure are partially delivered via the EXIT procedure, and arterial and venous cannulas are inserted while uteroplacental perfusion is maintained. Although CHD remains the most common disease entity considered for potential EXIT to ECMO therapy, this technique has been used for neonates with other disease processes associated with almost certain chance of immediate cardiorespiratory collapse after conventional delivery.

Access to the FETAL Airway

Most EXIT procedures are currently performed to access a compromised fetal airway before delivery; successful access depends on meticulous preoperative evaluation and careful preparation.^246,247 Portions of the trachea can be completely compressed and distorted such that even successful intubation may result in an inability to achieve adequate ventilation. For this reason, most surgeons perform a direct laryngoscopy and rigid bronchoscopy to examine the status of the fetal airway. In one series, successful endotracheal intubation by conventional means was reported in 77% of cases.²³⁰ In those cases in which tracheal intubation is impossible, a surgical tracheostomy can be performed as soon as the trachea is identified. The trachea can be located with the aid of preoperative radiographic studies, often identifying the tracheal location relative to fixed external anatomic landmarks. Gentle surgical palpation may also aid in the identification of cartilaginous tracheal rings. In cases in which the former options have failed, ultrasonography with the sterile probe inserted directly into the surgical incision may help to locate the trachea.²⁴⁸ When tracheal rings are identified, the trachea may be accessed directly with an endotracheal tube by tunneling through the fetal soft tissue, or with the aid of a retrograde wire inserted by the Seldinger technique. The trachea, exposed through a neck incision, may be incised via a temporary tracheotomy to allow passage of a feeding tube or wire from the trachea to the mouth or nose. The guidewire is then attached to the endotracheal tube, which is then pulled down into the proper position. After suturing the endotracheal tube securely to the mouth, the tracheotomy can then be closed.

Regardless of the method used to secure the trachea, the anesthesiologist must be prepared to control ventilation in the fetus. In some institutions, an anesthesiologist may be scrubbed at the operative field to assume this responsibility. In other institutions, one of the surgeons or neonatologists assumes this role. Adequate ventilation may be difficult to achieve for several reasons. Certain types of tumors, specifically cervical teratomas, may secrete thick mucus into the trachea, and this must be aggressively removed before ventilation. As soon as the airway is satisfactorily cleared, surfactant should be administered via the tracheal tube to diminish expected airway resistance. Surfactant is provided for two principal reasons. First, the majority of infants treated for such lesions are delivered at some point before term and their pulmonary development (considered both by gestational age and underlying pathophysiology) cannot be assumed to be normal. Second, the thick mucoid secretions and the aggressive lavage necessary to clear them may interrupt the normal surfactant layering and functionality, suggesting that surfactant therapy may provide a benefit if administered before lung ventilation. These steps should result in increases in fetal oxygen saturation to levels greater than 90%. If this does not occur, the position of the tracheal tube should be rechecked and the lungs should be auscultated with the aid of a sterile stethoscope. In addition, ultrasound examination for the presence of air bronchograms may be used to confirm tracheal intubation. Ventilation occurs most commonly with the aid of a sterile Jackson-Rees circuit. When adequate ventilation has been established, the fetus can be delivered.