Seminars in Fetal & Neonatal Medicine 15 (2010) 40–45 Contents lists available at ScienceDirect Seminars in Fetal & Neonatal Medicine journal homepage: www.elsevier.com/locate/sinyAnesthesia for fetal surgeryKha 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 yKeywords: Fetal surgery pushes the limits of knowledge and therapy beyond conventional paradigms by treating theFetal anesthesia developing fetus as a patient. Providing anesthesia for fetal surgery is challenging for many reasons. ItFetal surgery requires integration of both obstetric and pediatric anesthesia practice. Two patients must be anes-Fetal therapy thetized for the beneﬁt of one, and there is little margin for error. Many disciplines are involved, andPlacental circulation 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. Fetal surgery is a rapidly evolving discipline. The idea of treating Pregnancy also increases sensitivity to non-depolarizing musclethe fetus as a patient is not intuitive and has its roots in the 1960s relaxants.when intraperitoneal blood transfusions were performed for the Management of the airway of a pregnant woman is potentiallytreatment of erythroblastosis fetalis. Invasive surgical therapies in more difﬁcult. Engorgement of the airway mucosa has multiplehumans began in the 1980s after rigorous study in animal models. implications. Smaller endotracheal tubes must be used and nasalThese cases involved maternal laparotomy and hysterotomy to intubation may cause epistaxis. The potential for difﬁcult intuba-access and treat fetuses. The anesthetic techniques developed to tion is increased and airway complications are a signiﬁcant factor infacilitate these invasive procedures are based on the physiology of anesthesia-related morbidity and mortality.2–5 Oxygen consump-the pregnant woman and fetus and also are derived from an tion increases and functional residual capacity (FRC) decreases,understanding of the procedure to be performed. 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 Systemic2. Physiology vascular resistance is decreased by about 20% secondary to vaso- dilation and the addition of the placenta, a low-resistance circuit.2.1. Maternal Supine hypotension may result from aortocaval compression. During pregnancy, plasma volume increases relatively more than The physiologic changes of pregnancy impact anesthetic red blood cell volume increases, and hemoglobin concentrationsmanagement. Many organ systems are affected, the most relevant fall.being the neurologic, respiratory, cardiovascular, gastrointestinal, The pregnant patient is at risk for aspiration of gastric contents.and hematologic systems. Generally, maternal sensitivity to anes- Displacement of the stomach and decreased lower esophagealthetic agents is increased.1 Minimum alveolar concentration (MAC) sphincter tone may allow reﬂux of gastric contents. Intragastricfor isoﬂurane and halothane is lower in pregnancy. Increased pressure is highest in the third trimester. Gastric emptying of solidsdermatomal spread of epidural anesthetics is likely due to and liquids is slowed during labor.1 The coagulation system is in a state of accelerated, compensated intravascular coagulation. This hypercoagulable state is suggested * Children’s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, 9thFloor, Main Hospital, Philadelphia, PA 19104, USA. Tel.: þ1 215 590 1858; by an increase in the majority of coagulation factors, a decrease infax: þ1 215 590 1415. prothrombin and partial thromboplastin times, and a decrease in E-mail address: firstname.lastname@example.org antithrombin III. Increased ﬁbrinolysis is suggested by an increase1744-165X/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.doi:10.1016/j.siny.2009.05.004
K.M. Tran / Seminars in Fetal & Neonatal Medicine 15 (2010) 40–45 41of ﬁbrin degradation products. Attention must be paid to whereas phenylephrine could be used if the maternal heart ratethromboprophylaxis. were high. Neuraxial and general anesthetics have variable effects on2.2. Fetal uterine blood ﬂow. As long as maternal systemic pressure is maintained, epidural anesthesia does not alter uterine blood ﬂow Fetal physiology is complex. Neurologic pathways for cortical in elective cesarean sections.22 Pain and stress will decrease uterinetransmission of noxious stimuli in humans are still developing into blood ﬂow.23 Relief of pain with an epidural may attenuate thisthe third trimester.6 With both isoﬂurane and halothane, the reduction. Barring resultant hemodynamic changes, intravenousanesthetic requirement of fetal lambs is lower than that of a preg- induction agents (thiopental, propofol, etomidate, and ketamine)nant ewe.7,8 Perception and processing of pain is controversial, but do not affect uterine blood ﬂow greatly. Volatile anestheticsnoxious stimuli will elicit a physiologic response in the human decrease uterine tone and increase risk of bleeding.24 Light andfetus, as evidenced by increases in cortisol, b-endorphin, and moderate levels of volatile anesthesia will slightly depress blooddecreases in the pulsatility index of the fetal middle cerebral pressure, but uterine vasodilation maintains blood ﬂow. In a sheepartery.9 model of fetal surgery, with deeper levels of volatile anesthesia, The placenta acts as the organ of respiration, and a major role of uterine vasodilation cannot compensate for the reductions in bloodthe lung in utero is production of fetal lung ﬂuid. Restriction of pressure and cardiac output, and fetal acidosis occurs.25 However, itegress of this ﬂuid results in pulmonary hyperplasia, whereas is important to note that no medications were given to the preg-continuous drainage results in hypoplasia.10 nant ewes to support their blood pressure while undergoing The fetal circulation is notable for being a parallel system prior general anesthesia with high doses of volatile agent. Maternalto transitioning to a serial circulation at birth. The fetal myocar- hypocapnea or hyperventilation with positive pressure will likelydium has a higher proportion of non-contractile elements, and is decrease uterine blood ﬂow and fetal oxygen tension. Hypercapneaalso stiffer than adult myocardium.11 Increases in preload will may increase fetal oxygen tension.26provide minimal, if any, incremental increases of stroke volume Simple mechanical factors are important in the maintenance ofand cardiac output.12 Variation in heart rate provides a relatively uteroplacental perfusion and fetal oxygen delivery. Occlusion of thegreater contribution to variation in cardiac output. This lack of umbilical cord, either from loss of amniotic ﬂuid or from surgicalresponse to preload has been attributed to poor compliance of the manipulation, will cause rapid deterioration in the condition of themyocardium, but may also be due to extrinsic compression of the fetus. Likewise, integrity of the uteroplacental interface must alsofetal heart that is relieved with aeration of the lungs and clear- be maintained. Intraoperative separation of the placenta from theance of lung ﬂuid.13 uterus is catastrophic. The blood volume of a fetus varies during gestation. At 16–22weeks, blood volume of the fetoplacental unit has been estimated 2.4. Placental transportat 120–162 mL/kg of fetal weight.14,15 It is important to note thatabout two-thirds of the blood volume is contained on the placental Factors controlling placental drug transfer include size, lipidportion of the fetoplacental unit.16 solubility, protein-binding pKa, pH of fetal blood, and blood ﬂow. The coagulation system evolves throughout the fetal and High lipid solubility allows rapid transfer, but may result in trap-neonatal period. The fetus produces coagulation factors indepen- ping of drug in the placenta. Local anesthetics and opioids havedently of the mother, and these factors do not cross the placenta.17 higher acid dissociation constants and may be trapped in ionizedThe plasma concentrations of these proteins increase with form in the fetal circulation if the fetal pH is lower than the drug’sincreasing gestational age. pKa. Protein binding has a variable effect depending on the While in utero, fetal temperature is linked to maternal particular drug and protein interaction.temperature. A fetus exposed through a hysterotomy during open Although newer volatile anesthetics such as desﬂurane andsurgery needs to increase heat production, but it cannot. Mainte- sevoﬂurane have not been studied as thoroughly as halothane andnance of fetal normothermia during open surgery can be chal- isoﬂurane, the low molecular weight and lipid insolubility of theselenging due to the lack of shivering and non-shivering medications should allow rapid transfer with relatively high fetal/thermogenesis, the immature skin barrier, and increased evapora- maternal (F/M) ratios. Halothane and isoﬂurane have an F/M ratiotive losses. of 0.7–0.9 and 0.7 respectively.27,28 The F/M ratio of nitrous oxide is 0.83.292.3. Uteroplacental blood ﬂow Thiopental crosses rapidly into the fetal circulation, but F/M ratios range widely, between 0.4 and 1.1.30 Propofol has been The fetus depends on intact uteroplacental blood ﬂow and studied at both term and mid-gestation and F/M ratios rangepatent umbilical vessels for respiration and nutrition. Uterine blood between 0.5 and 0.85.30 Propofol infusions may be used forﬂow, while a surrogate for fetal oxygen delivery, does correlate with maternal sedation in early pregnancy for minimally invasivefetal umbilical venous PO2.18 Uterine blood ﬂow is directly related cases. Diazepam is a commonly used drug for maternal and fetalto uterine perfusion pressure (the difference between uterine sedation. Within minutes of injection the F/M ratio reaches unityarterial and venous pressure), and inversely related to uterine and ratios approach 2.0 after an hour.30 Midazolam has an F/Mvascular resistance. For fetal surgical procedures, maternal hypo- ratio of 0.76 at term30 and is gaining popularity in minimallytension, aortocaval compression, and uterine contractions decrease invasive cases. Morphine is also commonly used for maternal anduterine blood ﬂow. The effect of vasopressors, vasodilators, and fetal analgesia and sedation. The F/M ratio of fentanyl varied fromanesthetic agents on uterine blood ﬂow is variable because these 0.16 to 1.2 in one small study of maternal intravenous adminis-agents affect uterine arterial pressure and uterine vascular resis- tration.30 Remifentanil is a short-acting potent opioid that istance at the same time. Studies comparing ephedrine and phenyl- ﬁnding some use in both obstetric anesthesia and anesthesia forephrine for maintenance of blood pressure have shown no great fetal surgery.31clinical differences in neonatal outcome and lend slightly more Succinylcholine in large (300 mg) or repeated doses crossessupport to phenylephrine to support maternal blood pressure.19–21 the placenta and affects the fetus. Non-depolarizing muscleEphedrine is a logical choice if the maternal heart rate is low, relaxants and anticholinesterase agents are large, ionized
42 K.M. Tran / Seminars in Fetal & Neonatal Medicine 15 (2010) 40–45molecules that do not easily cross the placenta. Vecuronium F/M minimally invasive procedures, a multidisciplinary team meeting isratios are 0.06–0.11. Atropine readily crosses the placenta as held with the family to introduce the team, discuss the details, andopposed to glycopyrrolate which has a mean F/M ratio of 0.22. A address concerns from any of the parties.case of fetal bradycardia has been attributed to placental passageof neostigmine. Ephedrine crosses the placenta readily with an F/ 4.2. Preoperative preparationM ratio of 0.7.30 Preparation begins with the standard anesthetic history and3. Surgical issues physical examination. Speciﬁc questions for the mother should evaluate respiratory or circulatory compromise by the gravid3.1. Minimally invasive interventions uterus, as evidenced by symptoms of shortness of breath or light-headedness. More severe symptoms of aortocaval These are the most frequently performed fetal surgical proce- compression would call for meticulous left uterine displacementdures. The uterine cavity is accessed percutaneously with needles and would raise the level of suspicion in a mother with persis-and small sheaths. Visualization of structures is provided non- tent hypotension after induction of anesthesia. Severity ofinvasively by ultrasound and by fetoscopes inserted through the gastroesophageal reﬂux may change the anesthetic plan insheaths. Minimally invasive techniques allow for a wide range of minimally invasive cases where maternal sedation is considered.therapeutic options via a variety of operative techniques. Maternal imaging and blood work will be guided by the history The access may be as minor as one small gauge radiofrequency and physical examination. A type and screen is reasonable forprobe or may be as involved as multiple trocars for a robot-assisted most minimally invasive fetoscopic cases; open cases should notmyelomeningocele (MMC) repair in the fetal sheep model. Endo- proceed without cross-matched blood for the mother and typescopes range from 1.0 to 3.8 mm external diameter.32 The timing of O-negative blood for the fetus immediately available. Maternalthese procedures is typically in early or mid-gestation. antibodies to blood antigens can cross the placenta, and the O-negative blood for the fetus can be cross-matched with the3.2. Open mid-gestation surgery maternal sample. Speciﬁc fetal information is also needed. Location of the After induction of anesthesia, a maternal laparotomy is per- placenta affects patient positioning. The estimated fetal weight isformed. The location of this incision is usually transverse, but more used to determine dosage of fetal drugs. The actual disease processcephalad than that performed for a low-segment transverse and pathophysiology, and the extent of anatomic or physiologiccesarean section. The fetus is exposed, but only the necessary derangement, will give the providers an idea of the physiologicanatomy is delivered via the hysterotomy. For example, in an MMC reserve of the fetus. Fetal studies to elucidate the lesion and extentclosure, the lesion is exposed, while the rest of the fetus remains of physiologic derangements include ultrasound, echocardiog-bathed in amniotic ﬂuid in the uterus. If a fetal thoracotomy is raphy, and fetal magnetic resonance imaging. Serial studies trackplanned, an arm is delivered, and the shoulder and chest are the changes. Lung lesions may grow or shrink, airway compressionexposed while the rest of the fetus remains in the uterus. After may worsen or resolve, combined cardiac outputs may change,surgery and wound closure, the fetus is replaced in the uterus, and hydrops fetalis may ensue, and polyhydramnios may develop at anywarmed Ringer’s lactate is infused to restore amniotic volume. time.Antibiotics are also instilled into the amniotic ﬂuid. The uterus is Aspiration prophylaxis in the obstetric population includes oralclosed and a ﬂap of omentum is sewn over the uterine closure to sodium citrate, histamine receptor blockers or proton pumphelp seal it and prevent amniotic ﬂuid leakage. 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 proce- These cases are the most variable in the need for maternaldure has several key differences when compared with open mid- analgesia and anesthesia, and in the need for fetal analgesia orgestation cases. Since the fetus will be delivered at the end of the immobility. Communication with the surgical team is vital. Ancase, these procedures are performed at or near term to optimize anesthetic plan can range from local anesthetic inﬁltration tolung maturity. Before the umbilical cord is clamped, surgical sedation to neuraxial to general anesthesia. Medications can beintervention is performed that will allow successful transition to given directly to the mother by the anesthesia team and, thus,extrauterine life.33 This intervention may involve laryngoscopy, indirectly to the fetus by placental transfer. Medications can alsorigid bronchoscopy, intubation, tracheostomy, or it may involve be given directly to the fetus by the surgical team. Route of directresection of large lung lesions while on placental bypass.34 After administration can be variable; intramuscular, intravenous, andcompletion of the procedure, the newborn is managed by team intracardiac routes have been described.9,35,36 Maternal analgesiaheaded by a neonatologist for further resuscitation and manage- can often be accomplished with local anesthetic inﬁltration,ment in an intensive care unit. whereas in other cases, a neuraxial technique or general anes- thesia may be necessary. Fetal monitoring is typically limited4. Anesthetic plan to measurement of the fetal heart rate by the obstetricians with an ultrasound. Echocardiography may be used in cardiac4.1. Teamwork/communication interventions. Instrumentation for treatment of twin-to-twin transfusion Fetal surgical cases require teamwork. The disciplines that syndrome has shrunk in size and invasiveness has decreased.interact may include pediatric general surgery, obstetrics, pediatric Previously, at the author’s institution, these procedures wereanesthesia, obstetric anesthesia, cardiology, radiology, neonatology, performed with general anesthesia or neuraxial techniques. Theseneonatal nursing, and operating room nursing. At our institution, procedures are now done with sedation. The current practice atweekly meetings keep team members apprised of new patients and our institution includes maternal fasting, one intravenous (IV)new developments with existing patients. Before open or catheter, aspiration prophylaxis, and tocolysis with preoperative
K.M. Tran / Seminars in Fetal & Neonatal Medicine 15 (2010) 40–45 43indomethacin. Light sedation is administered to the mother to Intravenous crystalloid administration is kept to a minimumprovide maternal comfort and decreased fetal movement. Multiple because of the risk of maternal pulmonary edema after fetalregimens have been used successfully, including combinations of surgery.40 Administration of 500 mL of crystalloid for a case isopioids and other sedatives such as benzodiazepines or propofol. typical. Swings in blood pressure are likely to be exacerbated byIn a randomized double-blind trial comparing diazepam and restrictive administration of ﬂuids and frequent use of vasopres-remifentanil for fetal immobilization in minimally invasive sors. Clinically, the maternal blood pressure improves with exte-surgery, the remifentanil group (0.1 mg/kg/min) had signiﬁcantly riorization of the uterus and with surgical manipulation.less fetal movement and surgeons reported better operating Phenylephrine and ephedrine should be prepared. Vasopressorconditions.37 Initially tocolysis involved preoperative indometh- infusions allow for smoother blood pressure control. Centralacin, postoperative magnesium infusions, and post-discharge oral venous pressure measurement has guided ﬂuid therapy in thenifedipine or subcutaneous terbutaline. Post-discharge tocolysis is past, but has not been used recently.now rare. Severe intravenous ﬂuid restriction is no longer routine. After exposure of the fetus, an intramuscular injection ofPulmonary edema has been reported after fetoscopic surgery, but fentanyl (20 mg/kg), atropine (20 mg/kg), and vecuronium (0.2 mg/this case was more likely due to absorption of irrigation ﬂuids kg) is given by the surgical team. Amniotic ﬂuid is lost throughthrough venous channels in the myometrium than a capillary leak the hysterotomy, but is replaced with a continuous infusion ofphenomenon.38 Since surgical techniques vary, intravenous ﬂuid warmed Ringer’s lactate using a Level 1 infusion device. If fetal IVrestriction may be necessary, as well as a close accounting of access is necessary it is obtained, and IV tubing is handed over theirrigation used during these cases. drapes to the anesthesia team. Monitoring of the fetus in these By contrast with the anesthetic for complicated twin gesta- cases may include direct observation, heart rate by ultrasound,tions, providing anesthesia for balloon dilation of fetal aortic fetal echocardiography, and pulse oximetry.41,42 If a pulse oxi-stenosis involves maternal general endotracheal anesthesia and meter is placed by the surgical team, the hand is covered withintramuscular administration of fentanyl, vecuronium, and atro- sterile foil to prevent artifact from the operating room lights, andpine to the fetus.39 The potential risks of administration of a sterile cable is passed to the anesthesia team. Fetal oxygengeneral anesthesia in a pregnant woman are outweighed by the saturation ranges from 40% to 70%.43,44 Fetal echocardiographicneed for a completely immobile mother and fetus, along with the monitoring is continuous. Cardiac ﬁlling, contractility, and rate,potential need for fetal analgesia as the catheters and needles are along with patency of the ductus arteriosus, are helpful in anes-advanced through the fetal chest wall and heart. These two thetic management of the fetus. Umbilical blood gas measure-different techniques, both for minimally invasive surgery, illus- ment may be used in selected cases.trate the need for collaboration between the teams to prioritize The anesthesia team must watch closely for fetal bradycardia,needs and balance risks and beneﬁts to arrive at an optimal maternal or fetal bleeding, and maternal blood pressure changes.anesthetic plan. Careful observation and understanding of the events occurring in Strategies must be in place for failed procedures or fetal distress. the surgical ﬁeld is important. A decrease in fetal oxygen saturationThese plans will depend on the gestational age of the fetuses, their is an indicator of fetal distress.41 In the absence of a decrease in fetalprojected viability and preoperative discussion with the family. oxygen saturation, a common sign of fetal distress is bradycardia.Plans may range from supportive or palliative therapy to emergent Blood products should be readily available. Prior to resection ofcesarean delivery. large chest lesions, a transfusion of warm packed red blood cells may improve fetal hemodynamic stability. With closure of the4.4. Open mid-gestation uterus, tocolysis is begun with a bolus of IV magnesium sulfate, the epidural block is initiated, and the volatile anesthetic is reduced. Open mid-gestation surgery requires signiﬁcant uterine relax- The maternal abdomen is closed, and the mother is extubatedation. General endotracheal anesthesia with high-dose volatile awake.(two times the minimum alveolar concentration) is most often usedto achieve uterine relaxation for open surgery. Desﬂurane is the 4.5. EXITagent chosen at our institution because its low solubility allows forrapid emergence from deep anesthesia. Intravenous nitroglycerin Several key differences for the EXIT procedure are due to the factcan also be used to augment uterine relaxation. Relaxation allows that the fetus is to be delivered at the conclusion of the case.for easier fetal manipulation and decreases the likelihood of initi- Uterine relaxation is only needed intraoperatively, not post-ation of labor from uterine surgical manipulation. Relaxation may operatively. Magnesium sulfate is not given. Another difference isallow increased uterine blood ﬂow as long as maternal blood the need for two operating rooms and a resuscitation area for thepressure is maintained, and results in fetal exposure to some neonatal team. General endotracheal anesthesia is used at ourvolatile anesthetic agents. The mother is at risk for hypotension institution to provide high dose volatile anesthetics, but adequateboth from the anesthetic agents and from aortocaval compression. uterine relaxation with neuraxial anesthetic and nitroglycerinThe desired systemic blood pressure should be close to baseline. infusion has been reported.45,46 After the patient has been After fasting, placement of a peripheral IV line, oral tocolysis adequately anesthetized, the surgical team passes sterile items offand aspiration prophylaxis, a high lumbar epidural is placed for the ﬁeld for the anesthesia team. These may include tubing for IVpostoperative analgesia. A test dose of local anesthesia is given, ﬂuids, pulse oximeter cables, and oxygen tubing for a sterilebut if volatile anesthesia is used, no other local anesthetic is given Mapleson D circuit. Distinguishing fetal ﬂuids and medication fromuntil the end of the case. Under standard monitoring, left uterine maternal ﬂuids and drugs is important to avoid confusion espe-displacement, preoxygenation, rapid sequence induction and cially in emergent or urgent parts of the procedure. Fetal well-beingintubation take place. An orogastric tube, Foley catheter, and leg is monitored with pulse oximetry, heart rate, and possibly echo-compression devices are placed. Ventilation should maintain cardiography. Following maternal laparotomy, placental mappingnormocapnia. Because of the risk for rapid bleeding, a second and hysterotomy, the fetus is externalized as little as possible tolarge-bore peripheral IV line is placed. An arterial catheter is permit surgical approach to the lesion while continuing umbilicalplaced because small changes in maternal blood pressure may blood ﬂow. An intramuscular injection of narcotic and musclehave dramatic effects on fetal perfusion, heart rate and function. relaxant is given. Once the airway is secured or lesion resected,
44 K.M. Tran / Seminars in Fetal & Neonatal Medicine 15 (2010) 40–45surfactant is given to the fetus if premature and the lungs areventilated. It is important that no ventilation take place until the Practice pointsumbilical cord is ready to be divided. Increases in oxygen satura-tion, the presence of end-tidal CO2, and good chest movement are First do no harm: remember maternal safety.indicators of successful intubation. Fiberoptic bronchoscopy can be The anesthetic plan should be based on understandingalso be used as conﬁrmation. The baby is delivered for care by the of maternal and fetal physiology and the needs of the case.neonatal surgical team. Communication is vital. Once the umbilical cord is divided, uterine relaxation must be Minimally invasive cases present the widest range ofpromptly reversed. Administration of oxytocin and rapidly anesthetic possibilities.decreasing the inspired concentration of volatile anesthetic is Open mid-gestation cases require intense intraoperativeadequate in most cases, but methylergonovine and prostaglandin uterine relaxation and postoperative tocolysis.F2a should be readily available. After uterine tone is established, the EXIT procedures require intense intraoperative uterinehysterotomy is closed. After maternal hemodynamic stability is relaxation and planning for the post-EXIT care of theensured, the epidural catheter is dosed to provide postoperative neonate in the form of neonatology and secondaryanalgesia. The mother is extubated awake. operating room teams. Additional considerations for EXIT procedure include the pres-ence of both a neonatologist and a second operating room team.The neonatal team receives the newborn if the EXIT is technicallysuccessful, and the operating room team is prepared to take thenewborn and complete the surgery when the EXIT procedure is not Research directionssuccessful. Quantiﬁcation of human fetal exposure to anesthetic agents.4.6. Intraoperative fetal resuscitation Examination of the effects of anesthetics on the devel- oping brain. Fetal distress may occur during any surgical procedure and may Examination of the effects of surgical stress on the fetus.result from cord compression or kinking, placental separation, high Fetal outcome studies with various anesthetic techniques.uterine tone, maternal hypotension, hypoxia, or anemia. Fetalhypothermia, hypovolemia and anemia are also potential causes offetal distress. Cardiac dysfunction may result from prolongedexposure to high doses of volatile anesthetic agents. As with anychange in vital signs, the cause of the derangement must be sought Conﬂict of interest statementwhile therapy begins. Good condition of the mother must be ensured. The umbilical None declared.cord must be patent, aortocaval compression should be avoided,and the integrity of the uteroplacental unit must also be Funding sourcesconﬁrmed. Fetal distress and new-onset maternal hypotensionmay result from occult placental abruption. Ultrasound can be None.used to conﬁrm this diagnosis. Direct observation of the fetus canassist with these diagnoses. The surgical team will be able toconﬁrm adequate uterine relaxation, and fetal echocardiography Referenceswill inform the team about cardiac ﬁlling, function and patency ofthe ductus arteriosus. 1. Chang AB. Physiologic changes of pregnancy. In: Chestnut DH, editor. Obstetric anesthesia: principles and practice. 3rd ed. Philadelphia: Elsevier–Mosby; 2004. Measures to resuscitate the fetus will depend on how much p. 15–36.access the surgical and anesthesia teams have to the fetus, and 2. Goldszmidt E. Principles and practices of obstetric airway management. Anes-may range from simple measures, such as ensuring left uterine thesiol Clin 2008;26:109–25. vii.displacement or administration of maternal vasopressors, to 3. Munnur U, de Boisblanc B, Suresh MS. Airway problems in pregnancy. Crit Care Med 2005;33:S259–68.administration of medications or blood directly to the fetus. In 4. Ross BK. ASA closed claims in obstetrics: lessons learned. Anesthesiol Clin Northopen cases, emergency medications such as atropine and America 2003;21:183–97.epinephrine are given in a sterile fashion to the surgical team. 5. Rudra A, Mondal M, Acharya A, Nayak S, Mukherjee S. Anaesthesia-related maternal mortality. J Indian Med Assoc 2006;104:312–6.Medications can also be given intravenously or even intracardiac. 6. Lee SJ, Ralston HJ, Drey EA, Partridge JC, Rosen MA. Fetal pain: a systematic multidisciplinary review of the evidence. J Am Med Assoc 2005;294:947–54. 7. Bachman CR, Biehl DR, Sitar D, Cumming M, Pucci W. Isoﬂurane potency and cardiovascular effects during short exposures in the foetal lamb. Can Anaesth5. Pain, stress, and neurotoxicity Soc J 1986;33:41–7. 8. Gregory GA, Wade JG, Beihl DR, Ong BY, Sitar DS. Fetal anesthetic requirement These are highly controversial subjects. There is much debate (MAC) for halothane. Anesth Analg 1983;62:9–14. 9. Fisk NM, Gitau R, Teixeira JM, Giannakoulopoulos X, Cameron AD, Glover VA.about the perception of pain in the fetus.19 Invasive fetal proce- Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamicdures clearly elicit a stress response,9 and attenuation of this stress response to intrauterine needling. Anesthesiology 2001;95:828–35.response may be beneﬁcial.47 The long- and short-term effects of 10. Alcorn D, Adamson TM, Lambert TF, Maloney JE, Ritchie BC, Robinson PM. Morphological effects of chronic tracheal ligation and drainage in the fetal lambthis response continue to be studied, as well as the potentially lung. J Anat 1977;123:649–60.neurotoxic effects of the anesthetics used to block the stress 11. Rychik J. Fetal cardiovascular physiology. Pediatr Cardiol 2004;25:201–9.response.48 As procedures and anesthetic techniques evolve, work 12. Gilbert RD. Control of fetal cardiac output during changes in blood volume. Am Jshould be done to quantify human fetal exposure to anesthetic Phys 1980;238:H80–6. 13. Grant DA, Fauchere JC, Eede KJ, Tyberg JV, Walker AM. Left ventricular strokeagents and to explore the effects of these agents and surgical volume in the fetal sheep is limited by extracardiac constraint and arterialstress on the fetus. pressure. J Physiol 2001;535:231–9.
K.M. Tran / Seminars in Fetal Neonatal Medicine 15 (2010) 40–45 4514. Morris JA, Hustead RF, Robinson RG, Haswell GL. Measurement of fetoplacental 31. Kan RE, Hughes SC, Rosen MA, Kessin C, Preston PG, Lobo EP. Intravenous blood volume in the human previable fetus. Am J Obstet Gynecol 1974;118:927–34. remifentanil: placental transfer, maternal and neonatal effects. Anesthesiology15. Nicolaides KH, Clewell WH, Rodeck CH. Measurement of human fetoplacental 1998;88:1467–74. blood volume in erythroblastosis fetalis. Am J Obstet Gynecol 1987;157:50–3. 32. Klaritsch P, Albert K, Van Mieghem T, et al. Instrumental requirements for16. Yao AC, Moinian M, Lind J. Distribution of blood between infant and placenta minimal invasive fetal surgery. Br J Obstet Gynaecol 2009;116:188–97. after birth. Lancet 1969;2:871–3. 33. Mychaliska GB, Bealer JF, Graf JL, Rosen MA, Adzick NS, Harrison MR. Operating17. Cade JF, Hirsh J, Martin M. Placental barrier to coagulation factors: its relevance on placental support: the ex utero intrapartum treatment procedure. J Pediatr to the coagulation defect at birth and to haemorrhage in the newborn. Br Med J Surg 1997;32:227–30. discussion 230–1. 1969;2:281–3. 34. Hedrick HL, Flake AW, Crombleholme TM, et al. The ex utero intrapartum18. Bilardo CM, Nicolaides KH, Campbell S. Doppler measurements of fetal and therapy procedure for high-risk fetal lung lesions. J Pediatr Surg 2005;40: uteroplacental circulations: relationship with umbilical venous blood gases 1038–43. discussion 1044. measured at cordocentesis. Am J Obstet Gynecol 1990;162:115–20. 35. Mizrahi-Arnaud A, Tworetzky W, Bulich LA, et al. Pathophysiology, manage-19. Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized ment, and outcomes of fetal hemodynamic instability during prenatal cardiac controlled trials of ephedrine versus phenylephrine for the management of intervention. Pediatr Res 2007;62:325–30. hypotension during spinal anesthesia for cesarean delivery. Anesth Analg 36. Deprest J, Jani J, Gratacos E, et al. Fetal intervention for congenital diaphrag- 2002;94:920–6. table of contents. matic hernia: the European experience. Semin Perinatol 2005;29:94–103.20. Ngan Kee WD, Lee A, Khaw KS, Ng FF, Karmakar MK, Gin T. A randomized 37. Van de Velde M, Van Schoubroeck D, Lewi LE, et al. Remifentanil for fetal double-blinded comparison of phenylephrine and ephedrine infusion combi- immobilization and maternal sedation during fetoscopic surgery: a random- nations to maintain blood pressure during spinal anesthesia for cesarean ized, double-blind comparison with diazepam. Anesth Analg 2005;101:251–8. delivery: the effects on fetal acid–base status and hemodynamic control. Anesth table of contents. Analg 2008;107:1295–302. 38. Robinson MB, Crombleholme TM, Kurth CD. Maternal pulmonary edema during21. Thomas DG, Robson SC, Redfern N, Hughes D, Boys RJ. Randomized trial of bolus fetoscopic surgery. Anesth Analg 2008;107:1978–80. phenylephrine or ephedrine for maintenance of arterial pressure during spinal 39. Tworetzky W, Marshall AC. Balloon valvuloplasty for congenital heart disease in anaesthesia for caesarean section. Br J Anaesth 1996;76:61–5. the fetus. Clin Perinatol 2003;30:541–50.22. Alahuhta S, Rasanen J, Jouppila R, Jouppila P, Kangas-Saarela T, Hollmen AI. 40. DiFederico EM, Burlingame JM, Kilpatrick SJ, Harrison MR, Matthay MA. Uteroplacental and fetal haemodynamics during extradural anaesthesia for Pulmonary edema in obstetric patients is rapidly resolved except in the pres- caesarean section. Br J Anaesth 1991;66:319–23. ence of infection or of nitroglycerin tocolysis after open fetal surgery. Am J23. Shnider SM, Wright RG, Levinson G, et al. Uterine blood ﬂow and plasma Obstet Gynecol 1998;179:925–33. norepinephrine changes during maternal stress in the pregnant ewe. Anes- 41. Luks FI, Johnson BD, Papadakis K, Traore M, Piasecki GJ. Predictive value of thesiology 1979;50:524–7. monitoring parameters in fetal surgery. J Pediatr Surg 1998;33:1297–301.24. Cullen BF, Margolis AJ, Eger 2nd EI. The effects of anesthesia and pulmonary 42. Keswani SG, Crombleholme TM, Rychik J, et al. Impact of continuous intra- ventilation on blood loss during elective therapeutic abortion. Anesthesiology operative monitoring on outcomes in open fetal surgery. Fetal Diagn Ther 1970;32:108–13. 2005;20:316–20.25. Palahniuk RJ, Shnider SM. Maternal and fetal cardiovascular and acid–base 43. Helwig JT, Parer JT, Kilpatrick SJ, Laros Jr RK. Umbilical cord blood acid-base changes during halothane and isoﬂurane anesthesia in the pregnant ewe. state: what is normal? Am J Obstet Gynecol 1996;174:1807–12. discussion Anesthesiology 1974;41:462–72. 1812–4.26. Motoyama EK, Rivard G, Acheson F, Cook CD. The effect of changes in 44. Johnson N, Johnson VA, Fisher J, Jobbings B, Bannister J, Lilford RJ. Fetal maternal pH and P-CO2 on the P-O2 of fetal lambs. Anesthesiology monitoring with pulse oximetry. Br J Obstet Gynaecol 1991;98:36–41. 1967;28:891–903. 45. Clark KD, Viscomi CM, Lowell J, Chien EK. Nitroglycerin for relaxation to27. Kangas L, Erkkola R, Kanto J, Mansikka M. Halothane anaesthesia in caesarean establish a fetal airway (EXIT procedure). Obstet Gynecol 2004;103:1113–5. section. Acta Anaesthesiol Scand 1976;20:189–94. 46. George RB, Melnick AH, Rose EC, Habib AS. Case series: combined spinal28. Dwyer R, Fee JP, Moore J. Uptake of halothane and isoﬂurane by mother and epidural anesthesia for Cesarean delivery and ex utero intrapartum treatment baby during caesarean section. Br J Anaesth 1995;74:379–83. procedure. Can J Anaesth 2007;54:218–22.29. Polvi HJ, Pirhonen JP, Erkkola RU. Nitrous oxide inhalation: effects on maternal 47. White MC, Wolf AR. Pain and stress in the human fetus. Best Pract Res Clin and fetal circulations at term. Obstet Gynecol 1996;87:1045–8. Anaesthesiol 2004;18:205–20.30. Zakowski MI, Herman NL. The placenta: anatomy, physiology, and transfer of 48. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al. Early exposure to common drugs. In: Chestnut DH, editor. Obstetric anesthesia: principles and practice. 3rd anesthetic agents causes widespread neurodegeneration in the developing rat ed. Philadelphia: Elsevier–Mosby; 2004. p. 49–65. brain and persistent learning deﬁcits. J Neurosci 2003;23:876–82.