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Anesthesia for fetal surgery
Seminars in Fetal & Neonatal Medicine 15 (2010) 40–45
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Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny
Anesthesia for fetal surgery Kha M. Tran* Center for Fetal Diagnosis and Treatment, Children’s Hospital of Philadelphia, and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
s u m m a r y Keywords: Fetal anesthesia Fetal surgery Fetal therapy Placental circulation
Fetal surgery pushes the limits of knowledge and therapy beyond conventional paradigms by treating the developing fetus as a patient. Providing anesthesia for fetal surgery is challenging for many reasons. It requires integration of both obstetric and pediatric anesthesia practice. Two patients must be anesthetized for the benefit of one, and there is little margin for error. Many disciplines are involved, and communication must be effective. Conducting anesthetic research with vulnerable populations, such as pregnant women and their fetuses, is difficult, and many questions remain unanswered. Work must be done in the study of possible neurotoxicity caused by exposure of developing brain to anesthetic agents. The effects of stress on the developing fetus must also be further examined. Optimal anesthetic regimens remain to be determined. Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
increased nerve sensitivity, hormonal changes in pregnancy, reduced protein levels, and pH changes in the cerebrospinal fluid. Pregnancy also increases sensitivity to non-depolarizing muscle relaxants. Management of the airway of a pregnant woman is potentially more difficult. Engorgement of the airway mucosa has multiple implications. Smaller endotracheal tubes must be used and nasal intubation may cause epistaxis. The potential for difficult intubation is increased and airway complications are a significant factor in anesthesia-related morbidity and mortality.2–5 Oxygen consumption increases and functional residual capacity (FRC) decreases, increasing the risk for hypoxia. Pregnancy is a high cardiac output state. At term, cardiac output is increased by about 50% from non-pregnant values.1 Systemic vascular resistance is decreased by about 20% secondary to vasodilation and the addition of the placenta, a low-resistance circuit. Supine hypotension may result from aortocaval compression. During pregnancy, plasma volume increases relatively more than red blood cell volume increases, and hemoglobin concentrations fall. The pregnant patient is at risk for aspiration of gastric contents. Displacement of the stomach and decreased lower esophageal sphincter tone may allow reflux of gastric contents. Intragastric pressure is highest in the third trimester. Gastric emptying of solids and liquids is slowed during labor.1 The coagulation system is in a state of accelerated, compensated intravascular coagulation. This hypercoagulable state is suggested by an increase in the majority of coagulation factors, a decrease in prothrombin and partial thromboplastin times, and a decrease in antithrombin III. Increased fibrinolysis is suggested by an increase
Fetal surgery is a rapidly evolving discipline. The idea of treating the fetus as a patient is not intuitive and has its roots in the 1960s when intraperitoneal blood transfusions were performed for the treatment of erythroblastosis fetalis. Invasive surgical therapies in humans began in the 1980s after rigorous study in animal models. These cases involved maternal laparotomy and hysterotomy to access and treat fetuses. The anesthetic techniques developed to facilitate these invasive procedures are based on the physiology of the pregnant woman and fetus and also are derived from an understanding of the procedure to be performed.
2. Physiology 2.1. Maternal The physiologic changes of pregnancy impact anesthetic management. Many organ systems are affected, the most relevant being the neurologic, respiratory, cardiovascular, gastrointestinal, and hematologic systems. Generally, maternal sensitivity to anesthetic agents is increased.1 Minimum alveolar concentration (MAC) for isoflurane and halothane is lower in pregnancy. Increased dermatomal spread of epidural anesthetics is likely due to
* Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, 9th Floor, Main Hospital, Philadelphia, PA 19104, USA. Tel.: þ1 215 590 1858; fax: þ1 215 590 1415. E-mail address: [email protected] 1744-165X/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.siny.2009.05.004
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of fibrin degradation products. Attention must be paid to thromboprophylaxis. 2.2. Fetal Fetal physiology is complex. Neurologic pathways for cortical transmission of noxious stimuli in humans are still developing into the third trimester.6 With both isoflurane and halothane, the anesthetic requirement of fetal lambs is lower than that of a pregnant ewe.7,8 Perception and processing of pain is controversial, but noxious stimuli will elicit a physiologic response in the human fetus, as evidenced by increases in cortisol, b-endorphin, and decreases in the pulsatility index of the fetal middle cerebral artery.9 The placenta acts as the organ of respiration, and a major role of the lung in utero is production of fetal lung fluid. Restriction of egress of this fluid results in pulmonary hyperplasia, whereas continuous drainage results in hypoplasia.10 The fetal circulation is notable for being a parallel system prior to transitioning to a serial circulation at birth. The fetal myocardium has a higher proportion of non-contractile elements, and is also stiffer than adult myocardium.11 Increases in preload will provide minimal, if any, incremental increases of stroke volume and cardiac output.12 Variation in heart rate provides a relatively greater contribution to variation in cardiac output. This lack of response to preload has been attributed to poor compliance of the myocardium, but may also be due to extrinsic compression of the fetal heart that is relieved with aeration of the lungs and clearance of lung fluid.13 The blood volume of a fetus varies during gestation. At 16–22 weeks, blood volume of the fetoplacental unit has been estimated at 120–162 mL/kg of fetal weight.14,15 It is important to note that about two-thirds of the blood volume is contained on the placental portion of the fetoplacental unit.16 The coagulation system evolves throughout the fetal and neonatal period. The fetus produces coagulation factors independently of the mother, and these factors do not cross the placenta.17 The plasma concentrations of these proteins increase with increasing gestational age. While in utero, fetal temperature is linked to maternal temperature. A fetus exposed through a hysterotomy during open surgery needs to increase heat production, but it cannot. Maintenance of fetal normothermia during open surgery can be challenging due to the lack of shivering and non-shivering thermogenesis, the immature skin barrier, and increased evaporative losses. 2.3. Uteroplacental blood flow The fetus depends on intact uteroplacental blood flow and patent umbilical vessels for respiration and nutrition. Uterine blood flow, while a surrogate for fetal oxygen delivery, does correlate with fetal umbilical venous PO2.18 Uterine blood flow is directly related to uterine perfusion pressure (the difference between uterine arterial and venous pressure), and inversely related to uterine vascular resistance. For fetal surgical procedures, maternal hypotension, aortocaval compression, and uterine contractions decrease uterine blood flow. The effect of vasopressors, vasodilators, and anesthetic agents on uterine blood flow is variable because these agents affect uterine arterial pressure and uterine vascular resistance at the same time. Studies comparing ephedrine and phenylephrine for maintenance of blood pressure have shown no great clinical differences in neonatal outcome and lend slightly more support to phenylephrine to support maternal blood pressure.19–21 Ephedrine is a logical choice if the maternal heart rate is low,
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whereas phenylephrine could be used if the maternal heart rate were high. Neuraxial and general anesthetics have variable effects on uterine blood flow. As long as maternal systemic pressure is maintained, epidural anesthesia does not alter uterine blood flow in elective cesarean sections.22 Pain and stress will decrease uterine blood flow.23 Relief of pain with an epidural may attenuate this reduction. Barring resultant hemodynamic changes, intravenous induction agents (thiopental, propofol, etomidate, and ketamine) do not affect uterine blood flow greatly. Volatile anesthetics decrease uterine tone and increase risk of bleeding.24 Light and moderate levels of volatile anesthesia will slightly depress blood pressure, but uterine vasodilation maintains blood flow. In a sheep model of fetal surgery, with deeper levels of volatile anesthesia, uterine vasodilation cannot compensate for the reductions in blood pressure and cardiac output, and fetal acidosis occurs.25 However, it is important to note that no medications were given to the pregnant ewes to support their blood pressure while undergoing general anesthesia with high doses of volatile agent. Maternal hypocapnea or hyperventilation with positive pressure will likely decrease uterine blood flow and fetal oxygen tension. Hypercapnea may increase fetal oxygen tension.26 Simple mechanical factors are important in the maintenance of uteroplacental perfusion and fetal oxygen delivery. Occlusion of the umbilical cord, either from loss of amniotic fluid or from surgical manipulation, will cause rapid deterioration in the condition of the fetus. Likewise, integrity of the uteroplacental interface must also be maintained. Intraoperative separation of the placenta from the uterus is catastrophic. 2.4. Placental transport Factors controlling placental drug transfer include size, lipid solubility, protein-binding pKa, pH of fetal blood, and blood flow. High lipid solubility allows rapid transfer, but may result in trapping of drug in the placenta. Local anesthetics and opioids have higher acid dissociation constants and may be trapped in ionized form in the fetal circulation if the fetal pH is lower than the drug’s pKa. Protein binding has a variable effect depending on the particular drug and protein interaction. Although newer volatile anesthetics such as desflurane and sevoflurane have not been studied as thoroughly as halothane and isoflurane, the low molecular weight and lipid insolubility of these medications should allow rapid transfer with relatively high fetal/ maternal (F/M) ratios. Halothane and isoflurane have an F/M ratio of 0.7–0.9 and 0.7 respectively.27,28 The F/M ratio of nitrous oxide is 0.83.29 Thiopental crosses rapidly into the fetal circulation, but F/M ratios range widely, between 0.4 and 1.1.30 Propofol has been studied at both term and mid-gestation and F/M ratios range between 0.5 and 0.85.30 Propofol infusions may be used for maternal sedation in early pregnancy for minimally invasive cases. Diazepam is a commonly used drug for maternal and fetal sedation. Within minutes of injection the F/M ratio reaches unity and ratios approach 2.0 after an hour.30 Midazolam has an F/M ratio of 0.76 at term30 and is gaining popularity in minimally invasive cases. Morphine is also commonly used for maternal and fetal analgesia and sedation. The F/M ratio of fentanyl varied from 0.16 to 1.2 in one small study of maternal intravenous administration.30 Remifentanil is a short-acting potent opioid that is finding some use in both obstetric anesthesia and anesthesia for fetal surgery.31 Succinylcholine in large (300 mg) or repeated doses crosses the placenta and affects the fetus. Non-depolarizing muscle relaxants and anticholinesterase agents are large, ionized
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molecules that do not easily cross the placenta. Vecuronium F/M ratios are 0.06–0.11. Atropine readily crosses the placenta as opposed to glycopyrrolate which has a mean F/M ratio of 0.22. A case of fetal bradycardia has been attributed to placental passage of neostigmine. Ephedrine crosses the placenta readily with an F/ M ratio of 0.7.30
minimally invasive procedures, a multidisciplinary team meeting is held with the family to introduce the team, discuss the details, and address concerns from any of the parties. 4.2. Preoperative preparation
After induction of anesthesia, a maternal laparotomy is performed. The location of this incision is usually transverse, but more cephalad than that performed for a low-segment transverse cesarean section. The fetus is exposed, but only the necessary anatomy is delivered via the hysterotomy. For example, in an MMC closure, the lesion is exposed, while the rest of the fetus remains bathed in amniotic fluid in the uterus. If a fetal thoracotomy is planned, an arm is delivered, and the shoulder and chest are exposed while the rest of the fetus remains in the uterus. After surgery and wound closure, the fetus is replaced in the uterus, and warmed Ringer’s lactate is infused to restore amniotic volume. Antibiotics are also instilled into the amniotic fluid. The uterus is closed and a flap of omentum is sewn over the uterine closure to help seal it and prevent amniotic fluid leakage.
Preparation begins with the standard anesthetic history and physical examination. Specific questions for the mother should evaluate respiratory or circulatory compromise by the gravid uterus, as evidenced by symptoms of shortness of breath or light-headedness. More severe symptoms of aortocaval compression would call for meticulous left uterine displacement and would raise the level of suspicion in a mother with persistent hypotension after induction of anesthesia. Severity of gastroesophageal reflux may change the anesthetic plan in minimally invasive cases where maternal sedation is considered. Maternal imaging and blood work will be guided by the history and physical examination. A type and screen is reasonable for most minimally invasive fetoscopic cases; open cases should not proceed without cross-matched blood for the mother and type O-negative blood for the fetus immediately available. Maternal antibodies to blood antigens can cross the placenta, and the O-negative blood for the fetus can be cross-matched with the maternal sample. Specific fetal information is also needed. Location of the placenta affects patient positioning. The estimated fetal weight is used to determine dosage of fetal drugs. The actual disease process and pathophysiology, and the extent of anatomic or physiologic derangement, will give the providers an idea of the physiologic reserve of the fetus. Fetal studies to elucidate the lesion and extent of physiologic derangements include ultrasound, echocardiography, and fetal magnetic resonance imaging. Serial studies track the changes. Lung lesions may grow or shrink, airway compression may worsen or resolve, combined cardiac outputs may change, hydrops fetalis may ensue, and polyhydramnios may develop at any time. Aspiration prophylaxis in the obstetric population includes oral sodium citrate, histamine receptor blockers or proton pump inhibitors, and prokinetic agents such as metoclopramide.
3.3. Ex-utero intrapartum therapy (EXIT) procedure
4.3. Minimally invasive
Whereas both cases start in a similar fashion, the EXIT procedure has several key differences when compared with open midgestation cases. Since the fetus will be delivered at the end of the case, these procedures are performed at or near term to optimize lung maturity. Before the umbilical cord is clamped, surgical intervention is performed that will allow successful transition to extrauterine life.33 This intervention may involve laryngoscopy, rigid bronchoscopy, intubation, tracheostomy, or it may involve resection of large lung lesions while on placental bypass.34 After completion of the procedure, the newborn is managed by team headed by a neonatologist for further resuscitation and management in an intensive care unit.
These cases are the most variable in the need for maternal analgesia and anesthesia, and in the need for fetal analgesia or immobility. Communication with the surgical team is vital. An anesthetic plan can range from local anesthetic infiltration to sedation to neuraxial to general anesthesia. Medications can be given directly to the mother by the anesthesia team and, thus, indirectly to the fetus by placental transfer. Medications can also be given directly to the fetus by the surgical team. Route of direct administration can be variable; intramuscular, intravenous, and intracardiac routes have been described.9,35,36 Maternal analgesia can often be accomplished with local anesthetic infiltration, whereas in other cases, a neuraxial technique or general anesthesia may be necessary. Fetal monitoring is typically limited to measurement of the fetal heart rate by the obstetricians with an ultrasound. Echocardiography may be used in cardiac interventions. Instrumentation for treatment of twin-to-twin transfusion syndrome has shrunk in size and invasiveness has decreased. Previously, at the author’s institution, these procedures were performed with general anesthesia or neuraxial techniques. These procedures are now done with sedation. The current practice at our institution includes maternal fasting, one intravenous (IV) catheter, aspiration prophylaxis, and tocolysis with preoperative
3. Surgical issues 3.1. Minimally invasive interventions These are the most frequently performed fetal surgical procedures. The uterine cavity is accessed percutaneously with needles and small sheaths. Visualization of structures is provided noninvasively by ultrasound and by fetoscopes inserted through the sheaths. Minimally invasive techniques allow for a wide range of therapeutic options via a variety of operative techniques. The access may be as minor as one small gauge radiofrequency probe or may be as involved as multiple trocars for a robot-assisted myelomeningocele (MMC) repair in the fetal sheep model. Endoscopes range from 1.0 to 3.8 mm external diameter.32 The timing of these procedures is typically in early or mid-gestation. 3.2. Open mid-gestation surgery
4. Anesthetic plan 4.1. Teamwork/communication Fetal surgical cases require teamwork. The disciplines that interact may include pediatric general surgery, obstetrics, pediatric anesthesia, obstetric anesthesia, cardiology, radiology, neonatology, neonatal nursing, and operating room nursing. At our institution, weekly meetings keep team members apprised of new patients and new developments with existing patients. Before open or
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indomethacin. Light sedation is administered to the mother to provide maternal comfort and decreased fetal movement. Multiple regimens have been used successfully, including combinations of opioids and other sedatives such as benzodiazepines or propofol. In a randomized double-blind trial comparing diazepam and remifentanil for fetal immobilization in minimally invasive surgery, the remifentanil group (0.1 mg/kg/min) had significantly less fetal movement and surgeons reported better operating conditions.37 Initially tocolysis involved preoperative indomethacin, postoperative magnesium infusions, and post-discharge oral nifedipine or subcutaneous terbutaline. Post-discharge tocolysis is now rare. Severe intravenous fluid restriction is no longer routine. Pulmonary edema has been reported after fetoscopic surgery, but this case was more likely due to absorption of irrigation fluids through venous channels in the myometrium than a capillary leak phenomenon.38 Since surgical techniques vary, intravenous fluid restriction may be necessary, as well as a close accounting of irrigation used during these cases. By contrast with the anesthetic for complicated twin gestations, providing anesthesia for balloon dilation of fetal aortic stenosis involves maternal general endotracheal anesthesia and intramuscular administration of fentanyl, vecuronium, and atropine to the fetus.39 The potential risks of administration of general anesthesia in a pregnant woman are outweighed by the need for a completely immobile mother and fetus, along with the potential need for fetal analgesia as the catheters and needles are advanced through the fetal chest wall and heart. These two different techniques, both for minimally invasive surgery, illustrate the need for collaboration between the teams to prioritize needs and balance risks and benefits to arrive at an optimal anesthetic plan. Strategies must be in place for failed procedures or fetal distress. These plans will depend on the gestational age of the fetuses, their projected viability and preoperative discussion with the family. Plans may range from supportive or palliative therapy to emergent cesarean delivery. 4.4. Open mid-gestation Open mid-gestation surgery requires significant uterine relaxation. General endotracheal anesthesia with high-dose volatile (two times the minimum alveolar concentration) is most often used to achieve uterine relaxation for open surgery. Desflurane is the agent chosen at our institution because its low solubility allows for rapid emergence from deep anesthesia. Intravenous nitroglycerin can also be used to augment uterine relaxation. Relaxation allows for easier fetal manipulation and decreases the likelihood of initiation of labor from uterine surgical manipulation. Relaxation may allow increased uterine blood flow as long as maternal blood pressure is maintained, and results in fetal exposure to some volatile anesthetic agents. The mother is at risk for hypotension both from the anesthetic agents and from aortocaval compression. The desired systemic blood pressure should be close to baseline. After fasting, placement of a peripheral IV line, oral tocolysis and aspiration prophylaxis, a high lumbar epidural is placed for postoperative analgesia. A test dose of local anesthesia is given, but if volatile anesthesia is used, no other local anesthetic is given until the end of the case. Under standard monitoring, left uterine displacement, preoxygenation, rapid sequence induction and intubation take place. An orogastric tube, Foley catheter, and leg compression devices are placed. Ventilation should maintain normocapnia. Because of the risk for rapid bleeding, a second large-bore peripheral IV line is placed. An arterial catheter is placed because small changes in maternal blood pressure may have dramatic effects on fetal perfusion, heart rate and function.
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Intravenous crystalloid administration is kept to a minimum because of the risk of maternal pulmonary edema after fetal surgery.40 Administration of 500 mL of crystalloid for a case is typical. Swings in blood pressure are likely to be exacerbated by restrictive administration of fluids and frequent use of vasopressors. Clinically, the maternal blood pressure improves with exteriorization of the uterus and with surgical manipulation. Phenylephrine and ephedrine should be prepared. Vasopressor infusions allow for smoother blood pressure control. Central venous pressure measurement has guided fluid therapy in the past, but has not been used recently. After exposure of the fetus, an intramuscular injection of fentanyl (20 mg/kg), atropine (20 mg/kg), and vecuronium (0.2 mg/ kg) is given by the surgical team. Amniotic fluid is lost through the hysterotomy, but is replaced with a continuous infusion of warmed Ringer’s lactate using a Level 1 infusion device. If fetal IV access is necessary it is obtained, and IV tubing is handed over the drapes to the anesthesia team. Monitoring of the fetus in these cases may include direct observation, heart rate by ultrasound, fetal echocardiography, and pulse oximetry.41,42 If a pulse oximeter is placed by the surgical team, the hand is covered with sterile foil to prevent artifact from the operating room lights, and a sterile cable is passed to the anesthesia team. Fetal oxygen saturation ranges from 40% to 70%.43,44 Fetal echocardiographic monitoring is continuous. Cardiac filling, contractility, and rate, along with patency of the ductus arteriosus, are helpful in anesthetic management of the fetus. Umbilical blood gas measurement may be used in selected cases. The anesthesia team must watch closely for fetal bradycardia, maternal or fetal bleeding, and maternal blood pressure changes. Careful observation and understanding of the events occurring in the surgical field is important. A decrease in fetal oxygen saturation is an indicator of fetal distress.41 In the absence of a decrease in fetal oxygen saturation, a common sign of fetal distress is bradycardia. Blood products should be readily available. Prior to resection of large chest lesions, a transfusion of warm packed red blood cells may improve fetal hemodynamic stability. With closure of the uterus, tocolysis is begun with a bolus of IV magnesium sulfate, the epidural block is initiated, and the volatile anesthetic is reduced. The maternal abdomen is closed, and the mother is extubated awake. 4.5. EXIT Several key differences for the EXIT procedure are due to the fact that the fetus is to be delivered at the conclusion of the case. Uterine relaxation is only needed intraoperatively, not postoperatively. Magnesium sulfate is not given. Another difference is the need for two operating rooms and a resuscitation area for the neonatal team. General endotracheal anesthesia is used at our institution to provide high dose volatile anesthetics, but adequate uterine relaxation with neuraxial anesthetic and nitroglycerin infusion has been reported.45,46 After the patient has been adequately anesthetized, the surgical team passes sterile items off the field for the anesthesia team. These may include tubing for IV fluids, pulse oximeter cables, and oxygen tubing for a sterile Mapleson D circuit. Distinguishing fetal fluids and medication from maternal fluids and drugs is important to avoid confusion especially in emergent or urgent parts of the procedure. Fetal well-being is monitored with pulse oximetry, heart rate, and possibly echocardiography. Following maternal laparotomy, placental mapping and hysterotomy, the fetus is externalized as little as possible to permit surgical approach to the lesion while continuing umbilical blood flow. An intramuscular injection of narcotic and muscle relaxant is given. Once the airway is secured or lesion resected,
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surfactant is given to the fetus if premature and the lungs are ventilated. It is important that no ventilation take place until the umbilical cord is ready to be divided. Increases in oxygen saturation, the presence of end-tidal CO2, and good chest movement are indicators of successful intubation. Fiberoptic bronchoscopy can be also be used as confirmation. The baby is delivered for care by the neonatal surgical team. Once the umbilical cord is divided, uterine relaxation must be promptly reversed. Administration of oxytocin and rapidly decreasing the inspired concentration of volatile anesthetic is adequate in most cases, but methylergonovine and prostaglandin F2a should be readily available. After uterine tone is established, the hysterotomy is closed. After maternal hemodynamic stability is ensured, the epidural catheter is dosed to provide postoperative analgesia. The mother is extubated awake. Additional considerations for EXIT procedure include the presence of both a neonatologist and a second operating room team. The neonatal team receives the newborn if the EXIT is technically successful, and the operating room team is prepared to take the newborn and complete the surgery when the EXIT procedure is not successful.
4.6. Intraoperative fetal resuscitation Fetal distress may occur during any surgical procedure and may result from cord compression or kinking, placental separation, high uterine tone, maternal hypotension, hypoxia, or anemia. Fetal hypothermia, hypovolemia and anemia are also potential causes of fetal distress. Cardiac dysfunction may result from prolonged exposure to high doses of volatile anesthetic agents. As with any change in vital signs, the cause of the derangement must be sought while therapy begins. Good condition of the mother must be ensured. The umbilical cord must be patent, aortocaval compression should be avoided, and the integrity of the uteroplacental unit must also be confirmed. Fetal distress and new-onset maternal hypotension may result from occult placental abruption. Ultrasound can be used to confirm this diagnosis. Direct observation of the fetus can assist with these diagnoses. The surgical team will be able to confirm adequate uterine relaxation, and fetal echocardiography will inform the team about cardiac filling, function and patency of the ductus arteriosus. Measures to resuscitate the fetus will depend on how much access the surgical and anesthesia teams have to the fetus, and may range from simple measures, such as ensuring left uterine displacement or administration of maternal vasopressors, to administration of medications or blood directly to the fetus. In open cases, emergency medications such as atropine and epinephrine are given in a sterile fashion to the surgical team. Medications can also be given intravenously or even intracardiac.
5. Pain, stress, and neurotoxicity These are highly controversial subjects. There is much debate about the perception of pain in the fetus.19 Invasive fetal procedures clearly elicit a stress response,9 and attenuation of this response may be beneficial.47 The long- and short-term effects of this response continue to be studied, as well as the potentially neurotoxic effects of the anesthetics used to block the stress response.48 As procedures and anesthetic techniques evolve, work should be done to quantify human fetal exposure to anesthetic agents and to explore the effects of these agents and surgical stress on the fetus.
Practice points First do no harm: remember maternal safety. The anesthetic plan should be based on understanding of maternal and fetal physiology and the needs of the case. Communication is vital. Minimally invasive cases present the widest range of anesthetic possibilities. Open mid-gestation cases require intense intraoperative uterine relaxation and postoperative tocolysis. EXIT procedures require intense intraoperative uterine relaxation and planning for the post-EXIT care of the neonate in the form of neonatology and secondary operating room teams.
Research directions Quantification of human fetal exposure to anesthetic agents. Examination of the effects of anesthetics on the developing brain. Examination of the effects of surgical stress on the fetus. Fetal outcome studies with various anesthetic techniques.
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K.M. Tran / Seminars in Fetal & Neonatal Medicine 15 (2010) 40–45 14. Morris JA, Hustead RF, Robinson RG, Haswell GL. Measurement of fetoplacental blood volume in the human previable fetus. Am J Obstet Gynecol 1974;118:927–34. 15. Nicolaides KH, Clewell WH, Rodeck CH. Measurement of human fetoplacental blood volume in erythroblastosis fetalis. Am J Obstet Gynecol 1987;157:50–3. 16. Yao AC, Moinian M, Lind J. Distribution of blood between infant and placenta after birth. Lancet 1969;2:871–3. 17. Cade JF, Hirsh J, Martin M. Placental barrier to coagulation factors: its relevance to the coagulation defect at birth and to haemorrhage in the newborn. Br Med J 1969;2:281–3. 18. Bilardo CM, Nicolaides KH, Campbell S. Doppler measurements of fetal and uteroplacental circulations: relationship with umbilical venous blood gases measured at cordocentesis. Am J Obstet Gynecol 1990;162:115–20. 19. Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg 2002;94:920–6. table of contents. 20. Ngan Kee WD, Lee A, Khaw KS, Ng FF, Karmakar MK, Gin T. A randomized double-blinded comparison of phenylephrine and ephedrine infusion combinations to maintain blood pressure during spinal anesthesia for cesarean delivery: the effects on fetal acid–base status and hemodynamic control. Anesth Analg 2008;107:1295–302. 21. Thomas DG, Robson SC, Redfern N, Hughes D, Boys RJ. Randomized trial of bolus phenylephrine or ephedrine for maintenance of arterial pressure during spinal anaesthesia for caesarean section. Br J Anaesth 1996;76:61–5. 22. Alahuhta S, Rasanen J, Jouppila R, Jouppila P, Kangas-Saarela T, Hollmen AI. Uteroplacental and fetal haemodynamics during extradural anaesthesia for caesarean section. Br J Anaesth 1991;66:319–23. 23. Shnider SM, Wright RG, Levinson G, et al. Uterine blood flow and plasma norepinephrine changes during maternal stress in the pregnant ewe. Anesthesiology 1979;50:524–7. 24. Cullen BF, Margolis AJ, Eger 2nd EI. The effects of anesthesia and pulmonary ventilation on blood loss during elective therapeutic abortion. Anesthesiology 1970;32:108–13. 25. Palahniuk RJ, Shnider SM. Maternal and fetal cardiovascular and acid–base changes during halothane and isoflurane anesthesia in the pregnant ewe. Anesthesiology 1974;41:462–72. 26. Motoyama EK, Rivard G, Acheson F, Cook CD. The effect of changes in maternal pH and P-CO2 on the P-O2 of fetal lambs. Anesthesiology 1967;28:891–903. 27. Kangas L, Erkkola R, Kanto J, Mansikka M. Halothane anaesthesia in caesarean section. Acta Anaesthesiol Scand 1976;20:189–94. 28. Dwyer R, Fee JP, Moore J. Uptake of halothane and isoflurane by mother and baby during caesarean section. Br J Anaesth 1995;74:379–83. 29. Polvi HJ, Pirhonen JP, Erkkola RU. Nitrous oxide inhalation: effects on maternal and fetal circulations at term. Obstet Gynecol 1996;87:1045–8. 30. Zakowski MI, Herman NL. The placenta: anatomy, physiology, and transfer of drugs. In: Chestnut DH, editor. Obstetric anesthesia: principles and practice. 3rd ed. Philadelphia: Elsevier–Mosby; 2004. p. 49–65.
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31. Kan RE, Hughes SC, Rosen MA, Kessin C, Preston PG, Lobo EP. Intravenous remifentanil: placental transfer, maternal and neonatal effects. Anesthesiology 1998;88:1467–74. 32. Klaritsch P, Albert K, Van Mieghem T, et al. Instrumental requirements for minimal invasive fetal surgery. Br J Obstet Gynaecol 2009;116:188–97. 33. Mychaliska GB, Bealer JF, Graf JL, Rosen MA, Adzick NS, Harrison MR. Operating on placental support: the ex utero intrapartum treatment procedure. J Pediatr Surg 1997;32:227–30. discussion 230–1. 34. Hedrick HL, Flake AW, Crombleholme TM, et al. The ex utero intrapartum therapy procedure for high-risk fetal lung lesions. J Pediatr Surg 2005;40: 1038–43. discussion 1044. 35. Mizrahi-Arnaud A, Tworetzky W, Bulich LA, et al. Pathophysiology, management, and outcomes of fetal hemodynamic instability during prenatal cardiac intervention. Pediatr Res 2007;62:325–30. 36. Deprest J, Jani J, Gratacos E, et al. Fetal intervention for congenital diaphragmatic hernia: the European experience. Semin Perinatol 2005;29:94–103. 37. Van de Velde M, Van Schoubroeck D, Lewi LE, et al. Remifentanil for fetal immobilization and maternal sedation during fetoscopic surgery: a randomized, double-blind comparison with diazepam. Anesth Analg 2005;101:251–8. table of contents. 38. Robinson MB, Crombleholme TM, Kurth CD. Maternal pulmonary edema during fetoscopic surgery. Anesth Analg 2008;107:1978–80. 39. Tworetzky W, Marshall AC. Balloon valvuloplasty for congenital heart disease in the fetus. Clin Perinatol 2003;30:541–50. 40. DiFederico EM, Burlingame JM, Kilpatrick SJ, Harrison MR, Matthay MA. Pulmonary edema in obstetric patients is rapidly resolved except in the presence of infection or of nitroglycerin tocolysis after open fetal surgery. Am J Obstet Gynecol 1998;179:925–33. 41. Luks FI, Johnson BD, Papadakis K, Traore M, Piasecki GJ. Predictive value of monitoring parameters in fetal surgery. J Pediatr Surg 1998;33:1297–301. 42. Keswani SG, Crombleholme TM, Rychik J, et al. Impact of continuous intraoperative monitoring on outcomes in open fetal surgery. Fetal Diagn Ther 2005;20:316–20. 43. Helwig JT, Parer JT, Kilpatrick SJ, Laros Jr RK. Umbilical cord blood acid-base state: what is normal? Am J Obstet Gynecol 1996;174:1807–12. discussion 1812–4. 44. Johnson N, Johnson VA, Fisher J, Jobbings B, Bannister J, Lilford RJ. Fetal monitoring with pulse oximetry. Br J Obstet Gynaecol 1991;98:36–41. 45. Clark KD, Viscomi CM, Lowell J, Chien EK. Nitroglycerin for relaxation to establish a fetal airway (EXIT procedure). Obstet Gynecol 2004;103:1113–5. 46. George RB, Melnick AH, Rose EC, Habib AS. Case series: combined spinal epidural anesthesia for Cesarean delivery and ex utero intrapartum treatment procedure. Can J Anaesth 2007;54:218–22. 47. White MC, Wolf AR. Pain and stress in the human fetus. Best Pract Res Clin Anaesthesiol 2004;18:205–20. 48. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003;23:876–82.
Contents lists available at ScienceDirect
Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/siny
Anesthesia for fetal surgery Kha M. Tran* Center for Fetal Diagnosis and Treatment, Children’s Hospital of Philadelphia, and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
s u m m a r y Keywords: Fetal anesthesia Fetal surgery Fetal therapy Placental circulation
Fetal surgery pushes the limits of knowledge and therapy beyond conventional paradigms by treating the developing fetus as a patient. Providing anesthesia for fetal surgery is challenging for many reasons. It requires integration of both obstetric and pediatric anesthesia practice. Two patients must be anesthetized for the benefit of one, and there is little margin for error. Many disciplines are involved, and communication must be effective. Conducting anesthetic research with vulnerable populations, such as pregnant women and their fetuses, is difficult, and many questions remain unanswered. Work must be done in the study of possible neurotoxicity caused by exposure of developing brain to anesthetic agents. The effects of stress on the developing fetus must also be further examined. Optimal anesthetic regimens remain to be determined. Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
increased nerve sensitivity, hormonal changes in pregnancy, reduced protein levels, and pH changes in the cerebrospinal fluid. Pregnancy also increases sensitivity to non-depolarizing muscle relaxants. Management of the airway of a pregnant woman is potentially more difficult. Engorgement of the airway mucosa has multiple implications. Smaller endotracheal tubes must be used and nasal intubation may cause epistaxis. The potential for difficult intubation is increased and airway complications are a significant factor in anesthesia-related morbidity and mortality.2–5 Oxygen consumption increases and functional residual capacity (FRC) decreases, increasing the risk for hypoxia. Pregnancy is a high cardiac output state. At term, cardiac output is increased by about 50% from non-pregnant values.1 Systemic vascular resistance is decreased by about 20% secondary to vasodilation and the addition of the placenta, a low-resistance circuit. Supine hypotension may result from aortocaval compression. During pregnancy, plasma volume increases relatively more than red blood cell volume increases, and hemoglobin concentrations fall. The pregnant patient is at risk for aspiration of gastric contents. Displacement of the stomach and decreased lower esophageal sphincter tone may allow reflux of gastric contents. Intragastric pressure is highest in the third trimester. Gastric emptying of solids and liquids is slowed during labor.1 The coagulation system is in a state of accelerated, compensated intravascular coagulation. This hypercoagulable state is suggested by an increase in the majority of coagulation factors, a decrease in prothrombin and partial thromboplastin times, and a decrease in antithrombin III. Increased fibrinolysis is suggested by an increase
Fetal surgery is a rapidly evolving discipline. The idea of treating the fetus as a patient is not intuitive and has its roots in the 1960s when intraperitoneal blood transfusions were performed for the treatment of erythroblastosis fetalis. Invasive surgical therapies in humans began in the 1980s after rigorous study in animal models. These cases involved maternal laparotomy and hysterotomy to access and treat fetuses. The anesthetic techniques developed to facilitate these invasive procedures are based on the physiology of the pregnant woman and fetus and also are derived from an understanding of the procedure to be performed.
2. Physiology 2.1. Maternal The physiologic changes of pregnancy impact anesthetic management. Many organ systems are affected, the most relevant being the neurologic, respiratory, cardiovascular, gastrointestinal, and hematologic systems. Generally, maternal sensitivity to anesthetic agents is increased.1 Minimum alveolar concentration (MAC) for isoflurane and halothane is lower in pregnancy. Increased dermatomal spread of epidural anesthetics is likely due to
* Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, 9th Floor, Main Hospital, Philadelphia, PA 19104, USA. Tel.: þ1 215 590 1858; fax: þ1 215 590 1415. E-mail address: [email protected] 1744-165X/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.siny.2009.05.004
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of fibrin degradation products. Attention must be paid to thromboprophylaxis. 2.2. Fetal Fetal physiology is complex. Neurologic pathways for cortical transmission of noxious stimuli in humans are still developing into the third trimester.6 With both isoflurane and halothane, the anesthetic requirement of fetal lambs is lower than that of a pregnant ewe.7,8 Perception and processing of pain is controversial, but noxious stimuli will elicit a physiologic response in the human fetus, as evidenced by increases in cortisol, b-endorphin, and decreases in the pulsatility index of the fetal middle cerebral artery.9 The placenta acts as the organ of respiration, and a major role of the lung in utero is production of fetal lung fluid. Restriction of egress of this fluid results in pulmonary hyperplasia, whereas continuous drainage results in hypoplasia.10 The fetal circulation is notable for being a parallel system prior to transitioning to a serial circulation at birth. The fetal myocardium has a higher proportion of non-contractile elements, and is also stiffer than adult myocardium.11 Increases in preload will provide minimal, if any, incremental increases of stroke volume and cardiac output.12 Variation in heart rate provides a relatively greater contribution to variation in cardiac output. This lack of response to preload has been attributed to poor compliance of the myocardium, but may also be due to extrinsic compression of the fetal heart that is relieved with aeration of the lungs and clearance of lung fluid.13 The blood volume of a fetus varies during gestation. At 16–22 weeks, blood volume of the fetoplacental unit has been estimated at 120–162 mL/kg of fetal weight.14,15 It is important to note that about two-thirds of the blood volume is contained on the placental portion of the fetoplacental unit.16 The coagulation system evolves throughout the fetal and neonatal period. The fetus produces coagulation factors independently of the mother, and these factors do not cross the placenta.17 The plasma concentrations of these proteins increase with increasing gestational age. While in utero, fetal temperature is linked to maternal temperature. A fetus exposed through a hysterotomy during open surgery needs to increase heat production, but it cannot. Maintenance of fetal normothermia during open surgery can be challenging due to the lack of shivering and non-shivering thermogenesis, the immature skin barrier, and increased evaporative losses. 2.3. Uteroplacental blood flow The fetus depends on intact uteroplacental blood flow and patent umbilical vessels for respiration and nutrition. Uterine blood flow, while a surrogate for fetal oxygen delivery, does correlate with fetal umbilical venous PO2.18 Uterine blood flow is directly related to uterine perfusion pressure (the difference between uterine arterial and venous pressure), and inversely related to uterine vascular resistance. For fetal surgical procedures, maternal hypotension, aortocaval compression, and uterine contractions decrease uterine blood flow. The effect of vasopressors, vasodilators, and anesthetic agents on uterine blood flow is variable because these agents affect uterine arterial pressure and uterine vascular resistance at the same time. Studies comparing ephedrine and phenylephrine for maintenance of blood pressure have shown no great clinical differences in neonatal outcome and lend slightly more support to phenylephrine to support maternal blood pressure.19–21 Ephedrine is a logical choice if the maternal heart rate is low,
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whereas phenylephrine could be used if the maternal heart rate were high. Neuraxial and general anesthetics have variable effects on uterine blood flow. As long as maternal systemic pressure is maintained, epidural anesthesia does not alter uterine blood flow in elective cesarean sections.22 Pain and stress will decrease uterine blood flow.23 Relief of pain with an epidural may attenuate this reduction. Barring resultant hemodynamic changes, intravenous induction agents (thiopental, propofol, etomidate, and ketamine) do not affect uterine blood flow greatly. Volatile anesthetics decrease uterine tone and increase risk of bleeding.24 Light and moderate levels of volatile anesthesia will slightly depress blood pressure, but uterine vasodilation maintains blood flow. In a sheep model of fetal surgery, with deeper levels of volatile anesthesia, uterine vasodilation cannot compensate for the reductions in blood pressure and cardiac output, and fetal acidosis occurs.25 However, it is important to note that no medications were given to the pregnant ewes to support their blood pressure while undergoing general anesthesia with high doses of volatile agent. Maternal hypocapnea or hyperventilation with positive pressure will likely decrease uterine blood flow and fetal oxygen tension. Hypercapnea may increase fetal oxygen tension.26 Simple mechanical factors are important in the maintenance of uteroplacental perfusion and fetal oxygen delivery. Occlusion of the umbilical cord, either from loss of amniotic fluid or from surgical manipulation, will cause rapid deterioration in the condition of the fetus. Likewise, integrity of the uteroplacental interface must also be maintained. Intraoperative separation of the placenta from the uterus is catastrophic. 2.4. Placental transport Factors controlling placental drug transfer include size, lipid solubility, protein-binding pKa, pH of fetal blood, and blood flow. High lipid solubility allows rapid transfer, but may result in trapping of drug in the placenta. Local anesthetics and opioids have higher acid dissociation constants and may be trapped in ionized form in the fetal circulation if the fetal pH is lower than the drug’s pKa. Protein binding has a variable effect depending on the particular drug and protein interaction. Although newer volatile anesthetics such as desflurane and sevoflurane have not been studied as thoroughly as halothane and isoflurane, the low molecular weight and lipid insolubility of these medications should allow rapid transfer with relatively high fetal/ maternal (F/M) ratios. Halothane and isoflurane have an F/M ratio of 0.7–0.9 and 0.7 respectively.27,28 The F/M ratio of nitrous oxide is 0.83.29 Thiopental crosses rapidly into the fetal circulation, but F/M ratios range widely, between 0.4 and 1.1.30 Propofol has been studied at both term and mid-gestation and F/M ratios range between 0.5 and 0.85.30 Propofol infusions may be used for maternal sedation in early pregnancy for minimally invasive cases. Diazepam is a commonly used drug for maternal and fetal sedation. Within minutes of injection the F/M ratio reaches unity and ratios approach 2.0 after an hour.30 Midazolam has an F/M ratio of 0.76 at term30 and is gaining popularity in minimally invasive cases. Morphine is also commonly used for maternal and fetal analgesia and sedation. The F/M ratio of fentanyl varied from 0.16 to 1.2 in one small study of maternal intravenous administration.30 Remifentanil is a short-acting potent opioid that is finding some use in both obstetric anesthesia and anesthesia for fetal surgery.31 Succinylcholine in large (300 mg) or repeated doses crosses the placenta and affects the fetus. Non-depolarizing muscle relaxants and anticholinesterase agents are large, ionized
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molecules that do not easily cross the placenta. Vecuronium F/M ratios are 0.06–0.11. Atropine readily crosses the placenta as opposed to glycopyrrolate which has a mean F/M ratio of 0.22. A case of fetal bradycardia has been attributed to placental passage of neostigmine. Ephedrine crosses the placenta readily with an F/ M ratio of 0.7.30
minimally invasive procedures, a multidisciplinary team meeting is held with the family to introduce the team, discuss the details, and address concerns from any of the parties. 4.2. Preoperative preparation
After induction of anesthesia, a maternal laparotomy is performed. The location of this incision is usually transverse, but more cephalad than that performed for a low-segment transverse cesarean section. The fetus is exposed, but only the necessary anatomy is delivered via the hysterotomy. For example, in an MMC closure, the lesion is exposed, while the rest of the fetus remains bathed in amniotic fluid in the uterus. If a fetal thoracotomy is planned, an arm is delivered, and the shoulder and chest are exposed while the rest of the fetus remains in the uterus. After surgery and wound closure, the fetus is replaced in the uterus, and warmed Ringer’s lactate is infused to restore amniotic volume. Antibiotics are also instilled into the amniotic fluid. The uterus is closed and a flap of omentum is sewn over the uterine closure to help seal it and prevent amniotic fluid leakage.
Preparation begins with the standard anesthetic history and physical examination. Specific questions for the mother should evaluate respiratory or circulatory compromise by the gravid uterus, as evidenced by symptoms of shortness of breath or light-headedness. More severe symptoms of aortocaval compression would call for meticulous left uterine displacement and would raise the level of suspicion in a mother with persistent hypotension after induction of anesthesia. Severity of gastroesophageal reflux may change the anesthetic plan in minimally invasive cases where maternal sedation is considered. Maternal imaging and blood work will be guided by the history and physical examination. A type and screen is reasonable for most minimally invasive fetoscopic cases; open cases should not proceed without cross-matched blood for the mother and type O-negative blood for the fetus immediately available. Maternal antibodies to blood antigens can cross the placenta, and the O-negative blood for the fetus can be cross-matched with the maternal sample. Specific fetal information is also needed. Location of the placenta affects patient positioning. The estimated fetal weight is used to determine dosage of fetal drugs. The actual disease process and pathophysiology, and the extent of anatomic or physiologic derangement, will give the providers an idea of the physiologic reserve of the fetus. Fetal studies to elucidate the lesion and extent of physiologic derangements include ultrasound, echocardiography, and fetal magnetic resonance imaging. Serial studies track the changes. Lung lesions may grow or shrink, airway compression may worsen or resolve, combined cardiac outputs may change, hydrops fetalis may ensue, and polyhydramnios may develop at any time. Aspiration prophylaxis in the obstetric population includes oral sodium citrate, histamine receptor blockers or proton pump inhibitors, and prokinetic agents such as metoclopramide.
3.3. Ex-utero intrapartum therapy (EXIT) procedure
4.3. Minimally invasive
Whereas both cases start in a similar fashion, the EXIT procedure has several key differences when compared with open midgestation cases. Since the fetus will be delivered at the end of the case, these procedures are performed at or near term to optimize lung maturity. Before the umbilical cord is clamped, surgical intervention is performed that will allow successful transition to extrauterine life.33 This intervention may involve laryngoscopy, rigid bronchoscopy, intubation, tracheostomy, or it may involve resection of large lung lesions while on placental bypass.34 After completion of the procedure, the newborn is managed by team headed by a neonatologist for further resuscitation and management in an intensive care unit.
These cases are the most variable in the need for maternal analgesia and anesthesia, and in the need for fetal analgesia or immobility. Communication with the surgical team is vital. An anesthetic plan can range from local anesthetic infiltration to sedation to neuraxial to general anesthesia. Medications can be given directly to the mother by the anesthesia team and, thus, indirectly to the fetus by placental transfer. Medications can also be given directly to the fetus by the surgical team. Route of direct administration can be variable; intramuscular, intravenous, and intracardiac routes have been described.9,35,36 Maternal analgesia can often be accomplished with local anesthetic infiltration, whereas in other cases, a neuraxial technique or general anesthesia may be necessary. Fetal monitoring is typically limited to measurement of the fetal heart rate by the obstetricians with an ultrasound. Echocardiography may be used in cardiac interventions. Instrumentation for treatment of twin-to-twin transfusion syndrome has shrunk in size and invasiveness has decreased. Previously, at the author’s institution, these procedures were performed with general anesthesia or neuraxial techniques. These procedures are now done with sedation. The current practice at our institution includes maternal fasting, one intravenous (IV) catheter, aspiration prophylaxis, and tocolysis with preoperative
3. Surgical issues 3.1. Minimally invasive interventions These are the most frequently performed fetal surgical procedures. The uterine cavity is accessed percutaneously with needles and small sheaths. Visualization of structures is provided noninvasively by ultrasound and by fetoscopes inserted through the sheaths. Minimally invasive techniques allow for a wide range of therapeutic options via a variety of operative techniques. The access may be as minor as one small gauge radiofrequency probe or may be as involved as multiple trocars for a robot-assisted myelomeningocele (MMC) repair in the fetal sheep model. Endoscopes range from 1.0 to 3.8 mm external diameter.32 The timing of these procedures is typically in early or mid-gestation. 3.2. Open mid-gestation surgery
4. Anesthetic plan 4.1. Teamwork/communication Fetal surgical cases require teamwork. The disciplines that interact may include pediatric general surgery, obstetrics, pediatric anesthesia, obstetric anesthesia, cardiology, radiology, neonatology, neonatal nursing, and operating room nursing. At our institution, weekly meetings keep team members apprised of new patients and new developments with existing patients. Before open or
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indomethacin. Light sedation is administered to the mother to provide maternal comfort and decreased fetal movement. Multiple regimens have been used successfully, including combinations of opioids and other sedatives such as benzodiazepines or propofol. In a randomized double-blind trial comparing diazepam and remifentanil for fetal immobilization in minimally invasive surgery, the remifentanil group (0.1 mg/kg/min) had significantly less fetal movement and surgeons reported better operating conditions.37 Initially tocolysis involved preoperative indomethacin, postoperative magnesium infusions, and post-discharge oral nifedipine or subcutaneous terbutaline. Post-discharge tocolysis is now rare. Severe intravenous fluid restriction is no longer routine. Pulmonary edema has been reported after fetoscopic surgery, but this case was more likely due to absorption of irrigation fluids through venous channels in the myometrium than a capillary leak phenomenon.38 Since surgical techniques vary, intravenous fluid restriction may be necessary, as well as a close accounting of irrigation used during these cases. By contrast with the anesthetic for complicated twin gestations, providing anesthesia for balloon dilation of fetal aortic stenosis involves maternal general endotracheal anesthesia and intramuscular administration of fentanyl, vecuronium, and atropine to the fetus.39 The potential risks of administration of general anesthesia in a pregnant woman are outweighed by the need for a completely immobile mother and fetus, along with the potential need for fetal analgesia as the catheters and needles are advanced through the fetal chest wall and heart. These two different techniques, both for minimally invasive surgery, illustrate the need for collaboration between the teams to prioritize needs and balance risks and benefits to arrive at an optimal anesthetic plan. Strategies must be in place for failed procedures or fetal distress. These plans will depend on the gestational age of the fetuses, their projected viability and preoperative discussion with the family. Plans may range from supportive or palliative therapy to emergent cesarean delivery. 4.4. Open mid-gestation Open mid-gestation surgery requires significant uterine relaxation. General endotracheal anesthesia with high-dose volatile (two times the minimum alveolar concentration) is most often used to achieve uterine relaxation for open surgery. Desflurane is the agent chosen at our institution because its low solubility allows for rapid emergence from deep anesthesia. Intravenous nitroglycerin can also be used to augment uterine relaxation. Relaxation allows for easier fetal manipulation and decreases the likelihood of initiation of labor from uterine surgical manipulation. Relaxation may allow increased uterine blood flow as long as maternal blood pressure is maintained, and results in fetal exposure to some volatile anesthetic agents. The mother is at risk for hypotension both from the anesthetic agents and from aortocaval compression. The desired systemic blood pressure should be close to baseline. After fasting, placement of a peripheral IV line, oral tocolysis and aspiration prophylaxis, a high lumbar epidural is placed for postoperative analgesia. A test dose of local anesthesia is given, but if volatile anesthesia is used, no other local anesthetic is given until the end of the case. Under standard monitoring, left uterine displacement, preoxygenation, rapid sequence induction and intubation take place. An orogastric tube, Foley catheter, and leg compression devices are placed. Ventilation should maintain normocapnia. Because of the risk for rapid bleeding, a second large-bore peripheral IV line is placed. An arterial catheter is placed because small changes in maternal blood pressure may have dramatic effects on fetal perfusion, heart rate and function.
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Intravenous crystalloid administration is kept to a minimum because of the risk of maternal pulmonary edema after fetal surgery.40 Administration of 500 mL of crystalloid for a case is typical. Swings in blood pressure are likely to be exacerbated by restrictive administration of fluids and frequent use of vasopressors. Clinically, the maternal blood pressure improves with exteriorization of the uterus and with surgical manipulation. Phenylephrine and ephedrine should be prepared. Vasopressor infusions allow for smoother blood pressure control. Central venous pressure measurement has guided fluid therapy in the past, but has not been used recently. After exposure of the fetus, an intramuscular injection of fentanyl (20 mg/kg), atropine (20 mg/kg), and vecuronium (0.2 mg/ kg) is given by the surgical team. Amniotic fluid is lost through the hysterotomy, but is replaced with a continuous infusion of warmed Ringer’s lactate using a Level 1 infusion device. If fetal IV access is necessary it is obtained, and IV tubing is handed over the drapes to the anesthesia team. Monitoring of the fetus in these cases may include direct observation, heart rate by ultrasound, fetal echocardiography, and pulse oximetry.41,42 If a pulse oximeter is placed by the surgical team, the hand is covered with sterile foil to prevent artifact from the operating room lights, and a sterile cable is passed to the anesthesia team. Fetal oxygen saturation ranges from 40% to 70%.43,44 Fetal echocardiographic monitoring is continuous. Cardiac filling, contractility, and rate, along with patency of the ductus arteriosus, are helpful in anesthetic management of the fetus. Umbilical blood gas measurement may be used in selected cases. The anesthesia team must watch closely for fetal bradycardia, maternal or fetal bleeding, and maternal blood pressure changes. Careful observation and understanding of the events occurring in the surgical field is important. A decrease in fetal oxygen saturation is an indicator of fetal distress.41 In the absence of a decrease in fetal oxygen saturation, a common sign of fetal distress is bradycardia. Blood products should be readily available. Prior to resection of large chest lesions, a transfusion of warm packed red blood cells may improve fetal hemodynamic stability. With closure of the uterus, tocolysis is begun with a bolus of IV magnesium sulfate, the epidural block is initiated, and the volatile anesthetic is reduced. The maternal abdomen is closed, and the mother is extubated awake. 4.5. EXIT Several key differences for the EXIT procedure are due to the fact that the fetus is to be delivered at the conclusion of the case. Uterine relaxation is only needed intraoperatively, not postoperatively. Magnesium sulfate is not given. Another difference is the need for two operating rooms and a resuscitation area for the neonatal team. General endotracheal anesthesia is used at our institution to provide high dose volatile anesthetics, but adequate uterine relaxation with neuraxial anesthetic and nitroglycerin infusion has been reported.45,46 After the patient has been adequately anesthetized, the surgical team passes sterile items off the field for the anesthesia team. These may include tubing for IV fluids, pulse oximeter cables, and oxygen tubing for a sterile Mapleson D circuit. Distinguishing fetal fluids and medication from maternal fluids and drugs is important to avoid confusion especially in emergent or urgent parts of the procedure. Fetal well-being is monitored with pulse oximetry, heart rate, and possibly echocardiography. Following maternal laparotomy, placental mapping and hysterotomy, the fetus is externalized as little as possible to permit surgical approach to the lesion while continuing umbilical blood flow. An intramuscular injection of narcotic and muscle relaxant is given. Once the airway is secured or lesion resected,
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surfactant is given to the fetus if premature and the lungs are ventilated. It is important that no ventilation take place until the umbilical cord is ready to be divided. Increases in oxygen saturation, the presence of end-tidal CO2, and good chest movement are indicators of successful intubation. Fiberoptic bronchoscopy can be also be used as confirmation. The baby is delivered for care by the neonatal surgical team. Once the umbilical cord is divided, uterine relaxation must be promptly reversed. Administration of oxytocin and rapidly decreasing the inspired concentration of volatile anesthetic is adequate in most cases, but methylergonovine and prostaglandin F2a should be readily available. After uterine tone is established, the hysterotomy is closed. After maternal hemodynamic stability is ensured, the epidural catheter is dosed to provide postoperative analgesia. The mother is extubated awake. Additional considerations for EXIT procedure include the presence of both a neonatologist and a second operating room team. The neonatal team receives the newborn if the EXIT is technically successful, and the operating room team is prepared to take the newborn and complete the surgery when the EXIT procedure is not successful.
4.6. Intraoperative fetal resuscitation Fetal distress may occur during any surgical procedure and may result from cord compression or kinking, placental separation, high uterine tone, maternal hypotension, hypoxia, or anemia. Fetal hypothermia, hypovolemia and anemia are also potential causes of fetal distress. Cardiac dysfunction may result from prolonged exposure to high doses of volatile anesthetic agents. As with any change in vital signs, the cause of the derangement must be sought while therapy begins. Good condition of the mother must be ensured. The umbilical cord must be patent, aortocaval compression should be avoided, and the integrity of the uteroplacental unit must also be confirmed. Fetal distress and new-onset maternal hypotension may result from occult placental abruption. Ultrasound can be used to confirm this diagnosis. Direct observation of the fetus can assist with these diagnoses. The surgical team will be able to confirm adequate uterine relaxation, and fetal echocardiography will inform the team about cardiac filling, function and patency of the ductus arteriosus. Measures to resuscitate the fetus will depend on how much access the surgical and anesthesia teams have to the fetus, and may range from simple measures, such as ensuring left uterine displacement or administration of maternal vasopressors, to administration of medications or blood directly to the fetus. In open cases, emergency medications such as atropine and epinephrine are given in a sterile fashion to the surgical team. Medications can also be given intravenously or even intracardiac.
5. Pain, stress, and neurotoxicity These are highly controversial subjects. There is much debate about the perception of pain in the fetus.19 Invasive fetal procedures clearly elicit a stress response,9 and attenuation of this response may be beneficial.47 The long- and short-term effects of this response continue to be studied, as well as the potentially neurotoxic effects of the anesthetics used to block the stress response.48 As procedures and anesthetic techniques evolve, work should be done to quantify human fetal exposure to anesthetic agents and to explore the effects of these agents and surgical stress on the fetus.
Practice points First do no harm: remember maternal safety. The anesthetic plan should be based on understanding of maternal and fetal physiology and the needs of the case. Communication is vital. Minimally invasive cases present the widest range of anesthetic possibilities. Open mid-gestation cases require intense intraoperative uterine relaxation and postoperative tocolysis. EXIT procedures require intense intraoperative uterine relaxation and planning for the post-EXIT care of the neonate in the form of neonatology and secondary operating room teams.
Research directions Quantification of human fetal exposure to anesthetic agents. Examination of the effects of anesthetics on the developing brain. Examination of the effects of surgical stress on the fetus. Fetal outcome studies with various anesthetic techniques.
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