ANESTHESIA FOR

FOETAL SURGERY
Dr. Athira S Madhu
INTRODUCTION
 Most fetal abnormalities are not appropriate for antenatal intervention and are
more amenable to treatment after delivery
 Some anatomic malformations may result in irreversible end-organ damage and
would benefit from intervention before birth.
 Surgical or procedural correction in utero could allow normal fetal development
and might mitigate much of the detrimental pathologic process observed.
 Other defects, such as congenital airway obstruction, can be managed intrapartum
by keeping the uteroplacental unit intact while the defect is repaired or airway
secured, without the urgency that would be associated with attempting similar
procedures immediately after birth.
HISTORY
 Initial pioneers in the field of fetal therapy include Sir (Albert) William Liley.
 In the early 1960s, Liley was the first to successfully treat erythroblastosis fetalis
with an intraperitoneal blood transfusion that allowed the transfused red cells to be
absorbed into the fetal circulation through the subdiaphragmatic lymphatics and
thoracic duct.
 In the early 1970s, Liggins administered corticosteroids to the fetus via the
maternal circulation to increase surfactant production in preterm
fetuses at risk for respiratory distress syndrome.
 Harrison and colleagues performed the first successful human fetal surgery by
creating a vesicostomy in a fetus with a congenital lower urinary tract
obstruction resulting in bilateral hydronephrosis.
 Father of open fetal surgery :Dr. Michael Harrison
1. Anatomic lessons that interfere 2. Anomalies associated with twins
with development • TTTS
 Obstructive uropathy • Twin reverse arterial perfusion
 Congenital diaphragmatic hernia
 Cardiac anomalies: complete heart
block, AS, PS
 Neural tube defects
3. Anomalies of placenta, cord or
 Thoracic SOL membranes
 Giant neck masses • Amniotic band
 Tracheal atresia-stenosis • Chorioangioma
 Congenital adenomatoid
malformations
PREREQUISITE GUIDELINES FOR FETAL
SURGERY
(1) the fetal lesion is accurately diagnosed;

(2) the progression and severity of the anomaly is predictable and well understood
(3) other severe associated anomalies that would contraindicate fetal intervention
are excluded

(4) if left untreated before birth, the fetal abnormality would lead to fetal demise,
irreversible organ damage, or severe postnatal morbidity, and, therefore, intervening
before birth would benefit the neonatal outcome; and

(5) the maternal risk is acceptably infrequent.

 All interventions should be preceded by a thorough multidisciplinary team
deliberation of the clinical case.
 Discussions should focus on a comprehensive risk benefit analysis
 providing the family appropriate counseling that includes options for elective
termination of pregnancy or continuation of pregnancy without fetal therapy.
 Potential risks to the mother should be part of the informed consent
 thorough and detailed maternal preoperative evaluation to ensure maternal risks
are minimal.
CLASSIFICATION
 Fetal surgery is broadly categorized into three types of intervention:
1. Minimally invasive procedures
2. Open procedures
3. Intrapartum procedures.
MINIMALLY INVASIVE FETAL PROCEDURES
(1) percutaneous interventions : guided by ultrasound, also known as fetal image–
guided surgery for intervention or therapy (FIGS-IT)
(2) fetal endoscopic surgery : using small endoscopic instruments dually guided by
direct fetoscopic camera view and simultaneous real-time usg imaging
typically accomplished percutaneously, but sometimes requires a small
maternal minilaparotomy.
 risks for preterm labor and delivery are reduced compared with those in open
procedures that include a hysterotomy.
 Unlike in open fetal procedures, the mother can safely undergo a vaginal delivery
for this and future pregnancies.
 risk for preterm premature rupture of membrane (PPROM) remains significant.
OPEN FETAL PROCEDURES
 involve a maternal laparotomy, a hysterotomy, and the need for intraoperative
uterine relaxation
 incur significantly more risk to both the fetus and mother than minimally invasive
procedures.
 Cesarean delivery is required after an open fetal procedure and for all future
pregnancies owing to the increased risk for uterine dehiscence or rupture at the
site of the hysterotomy.
 Indications for Open fetal surgery
CCAM : congenital cystic adenomatoid malformations of lung : lobectomy
Sacrococcygeal teratoma: resection
Meningomyelocoele: repair
CDH: temporary tracheal occlusion
Obstructive hydronephrosis : vesicostomy, ureterostomy
 increased risks include • Additional maternal and fetal risks include :

• PPROM, • the anesthetic risks noted for nonobstetric

• oligohydramnios, surgery during pregnancy ,
• preterm laborand delivery, • pulmonary edema,
• uterine rupture, and • hemorrhage,
• fetal mortality. • membrane separation,
• chorioamnionitis.
 For fetuses with known airway compromise or obstruction,
 allows continued fetal support by the intact uteroplcental unit (placental bypass)
while the fetal airway is secured or other procedures completed without the
concern for postnatal respiratory compromise, hypoxia, and asphyxia.
 ECMO can be initiated during an EXIT procedure for a fetus with significant
cardiopulmonary disease.
 Fetal surgical procedures in excess of 2.5 hours have been successfully performed
using placental bypass with normal umbilical cord carbon dioxide and pH values
at delivery.
 Maternal safety is the primary focus when determining a plan that will optimize
fetal outcome.
 Participation of the anesthesiologist is critical to preoperative maternal assessment
to determine whether maternal risk is acceptably infrequent for potential fetal
benefit.
 Maternal counseling regarding risks and benefits of the procedure should be
thorough and unbiased and convey the most recent outcome and complication data
about the planned intervention.
 The team must convey the specific condition’s natural history and diagnostic
limitations and whether associated anomalies are detected
 Discussions should focus on specific implications to the mother, the pregnancy, the
fetus, postnatal care, future pregnancies, any data regarding intermediate and
long-term outcomes for the proposed intervention, and all alternatives
 Similar discussions also should include alternative options such as nonintervention
and the possibility of pregnancy termination if applicable.
 Mothers should be informed about the planned timing and method of delivery,
future reproductive implications, and—if a hysterotomy is planned—the risk for
uterine rupture and need for cesarean delivery with this and all future pregnancies
 Fertility does not appear to be affected by open fetal surgery, but the risk for
uterine rupture or dehiscence before delivery is significant and comparable or
even greater than that asso-
ciated with a prior cesarean delivery performed with a classic incision
 If the fetus is of viable gestational age, additional counseling is required about the
mother’s wishes for possible emergent delivery and neonatal resuscitation in the
event of unplanned fetal distress unresponsive to in utero treatment.
in addition to maternal considerations for anesthetic administration during preg-
nancy, it is essential to understand the impact of surgery and anesthetic administration on fetal physiology,
methods for fetal analgesia and anesthesia, techniques for fetal monitoring, intraoperative anesthetic
management, and postoperative care for both mother and fetus.
 Cardiovascular:
Fetal cardiac output depends primarily on heart rate
Fetal myocardium is less compliant than adult myocar-dium, with changes in preload
having minimal effect on cardiac output.
Constraining forces of the fluid-filled lungs also limit ventricular filling and restrict
increases in cardiac output in response to additional preload
The normal fetal cardiac output (sum of right and left ventricular output) is in the
range of 425 to 550 mL/min/kg throughout gestation
 Fetal blood volume increases during gestation, and approximately two thirds of the
fetal-placental blood volume resides within the placenta
 During the second trimester, fetal blood volume is estimated to be approximately
120 to 160 mL/kg of fetal body weight
 After midgestation, fetal blood volume can be estimated based on gestational age
(GA) using the equation,
estimated fetal blood volume (mL) = 11.2 × GA − 209.4
 In normal pregnancy, the mean fetal Hb increases linearly from 11 g/dL at 17
weeks gestation to 15 g/dL at 40 weeks
 Manipulation of the fetus or umbilical cord during open fetal procedures can affect
fetal cardiac output, regional distribution of fetal circulation, or blood flow in the
umbilical cord
 During open procedures, the fetal circulation can be severely impaired by direct
compression of the umbilical cord, inferior vena cava, or mediastinum.
 Fetal heart rate (FHR) monitoring during minimally invasive procedures is also
important.
 The placenta, receives nearly half the fetal cardiac output, is responsible for
respiratory gas exchange.
 , the lungs receive little blood fl ow and the pulmonary and systemic circulations
are parallel instead of in series, as in the adult
 This arrangement is made possible by two cardiac shunts—the foramen ovale and
the ductus arteriosus:
 Well-oxygenated blood from the placenta(approximately 80% oxygen saturation)
mixes with venous blood returning from the lower body (25% oxygen saturation)
and flows via the inferior vena cava into the right atrium.
 2. Right atrial anatomy preferentially directs blood flow from the inferior vena cava
(67% oxygen saturation) through the foramen ovale into the left atrium.
 3. Left atrial blood is then pumped by the left ventricle to the upper body (mainly
the brain and the heart).
 4. Poorly oxygenated blood from the upper body returns via the superior vena cava
to the right atrium.
 Right atrial anatomy preferentially directs fl ow from the superior vena cava into
the right ventricle.
 6. Right ventricular blood is pumped into the pulmonary artery.
 7. Because of high pulmonary vascular resistance, 95% of the blood ejected from
the right ventricle (60% oxygen saturation) is shunted across the ductus arteriosus,
into the descending aorta, and back to the placenta and lower body.
 Th e parallel circulation results in unequal ventricular fl ows; the right ventricle
ejects two thirds of the combined ventricular outputs, whereas the left ventricle
ejects only one third.
 Up to 50% of the well-oxygenated blood in the umbilical vein can pass directly to
the heart via the ductus venosus, bypassing the liver.
 Th e remainder of the blood fl ow from the placenta mixes with blood from the
portal vein (via the portal sinus ) and passes through the liver before reaching the
heart.
 important in allowing relatively rapid hepatic degradation of drugs (or toxins) that
are absorbed from the maternal circulation.
 fetal circulation, which is established very early during intrauterine life, maturation
of the lungs lags behind.
 Extrauterine survival is not possible until aft er 24–25 weeks of gestation, when
pulmonary capillaries are formed and come to lie in close approximation to an
immature alveolar epithelium.
 At 30 weeks, the cuboidal alveolar epithelium fl attens out and begins to produce
pulmonary surfactant.
 Sufficient pulmonary surfactant is usually present aft er 34 weeks of gestation.
 Administration of glucocorticoids to the mother may accelerate fetal surfactant
production.
 Th e most profound adaptive changes at birth involve the circulatory and respiratory
systems. Failure to make this transition successfully results in fetal death or permanent
neurological damage.
 At term, the fetal lungs are developed but contain about 90 mL of a plasma ultrafi ltrate
 . During expul-sion of the fetus at delivery, this fl uid is normally squeezed from the
lungs by the forces of the pelvic muscles and the vagina acting on the baby (the vaginal
squeeze)
 Any remaining fl uid is reabsorbed by the pulmonary capillaries and lymphatics.
 Small (preterm) neonates and neonates delivered via cesarean section do not benefi t
from the vaginal squeeze and thus typically have greater diffi culty in maintaining
respirations (transient tachypnea of the newborn).
 Respiratory eff orts are normally initiated within 30 s after birth and become sustained
within 90 s.
 Mild hypoxia and acidosis as well as sensory stimulation—cord clamping, pain,
touch, and noise—help initiateand sustain respirations, whereas the outward recoil
of the chest at delivery aids in fi lling the lungs with air.
 Lung expansion increases both alveolar and arterial oxygen tensions and
decreases pulmonary vascular resistance.
 Th e increase in oxygen tension is a potent stimulus for pulmonary arterial
vasodilation.
 Th e resultant increase in pulmonary blood fl ow and augmented fl ow to the left
heart elevates left atrial pressure and functionally closes the foramen ovale.
 The increase in arterial oxygen tension also causes the ductus arteriosus to
contract and functionally close.
 Other chemical mediators that may play a role in ductal closure include
acetylcholine, bradykinin, and prostaglandins.
 Th e overall result is elimination of right-to-left shunting and establishment of the
adult circulation
 Anatomic closure of the ductus arteriosus does not usually occur until about 2–3
weeks, whereas closure of the foramen ovale takes months if it occurs at all.
 Hypoxia or acidosis during the fi rst few days of life can prevent or reverse these
physiological changes, resulting in persistence of (or return to) the fetal circulation,
or persistent pulmonary hypertension of the newborn.
 A vicious circle is established where the right-to-left shunting promotes hypoxemia
and acidosis, which in turn promote more shunting
 Right-to-left shunting may occur across the foramen ovale, the ductus arteriosus, or
both.
 Unless this circle is broken, neonatal demise can occur rapidly.
 Lung:Fetal lung epithelium produces more than 100 mL/kg/day of fluid that fills the
lungs and facilitates appropriate pulmonary growth and development.
 Excess lung fluid exits the trachea and is either swallowed or flows into the
amniotic fluid.

 GIT: Although fetal liver function is immature coagulation factors are synthesized
independent of the maternal circulation and do not cross the placenta.
 The serum concentrations of these factors increase with gestational age but fetal
clot formation in response to tissue injury is decreased in contrast to that in adults
throughout gestation
 During fetal surgery, procedural and pharmacologic inter-ventions can adversely
affect fetal physiology directly or affect it indirectly by alterations in uteroplacental
or fetoplacental circulation and gas exchange.
 Appropriate fetal monitoring facilitates early intervention.
 Changes in anesthetic technique, adjustment of maternal hemodynamics, and
early initiation of in utero resuscitation of the fetus can decrease the risk for
intraoperative fetal hypoxia, hemodynamic compromise, or demise.
During labor, during fetal procedures,

FHR monitoring with external Echocardiography

Doppler or a fetal scalp electrode is pulse oximetry,
commonly employed to assess fetal ultra-sound imaging of umbilical artery
well-being. flow are the primary methods for fetal
assessment.

FHR deceleration has been shown to

precede fetal Hb desaturation with use
of fetal pulse oximetry monitoring
during labor
 Intraoperative ultrasonography allows imaging of FHR, cardiac contractility, and
cardiac filling, as well as Doppler assessment of umbilical cord flow.
 Both absent and reversed umbilical artery diastolic flow are associated with
increased perinatal morbidity and mortality
 When prolonged fetal bradycardia, Hb desaturation, or significant changes in
umbilical artery flow dynamics occur during a fetal procedure, steps should be
undertaken promptly to improve uterine perfusion, ensure the uteroplacental
interface is intact, and relieve any compression of the umbilical cord or placenta
 In some cases, ex utero fetal resuscitation may be necessary if the fetus was
previously determined to be of a viable gestational age.
 Temparature: In utero, the fetus is unable to thermoregulate and depends on
maternal body temperature. Induction of general anesthesia, surgical exposure,
and hysterotomy can reduce fetal temperature dramatically
 hypothermia with fetal bradycardia
 During minimally invasive procedure: monitoring of temperature and maintenance
of maternal euthermia with use of forced air warming likely improves fetal well-
being during
 During open fetal surgery, use of warmed fluid for intrauterine irrigation and
monitoring of both maternal core and amniotic fluid temperatures are also
important
 The capability of the fetus to perceive pain remains controversial
 The fetus exhibits pituitary-adrenal, sympa-thoadrenal, and circulatory stress
responses to noxious stimuli as early as 18 weeks gestation.
 fetuses are unlikely to experience pain before 24 weeks gestation because the
cortex requires additional growth and development to establish the extensive
neural network of pathways to other central nervous system (CNS) structures.
 Although invasive fetal procedures elicit a stress response, this response is
mediated at the level of the spinal cord, brainstem, and/or basal ganglia and does
not necessarily correlate with conscious perception of pain that requires the cortex
 Providing adequate anesthesia and analgesia is associated with both attenuation of the
deleterious effects and improved outcomes
 Stress responses secondary to invasive fetal procedures are blunted with opioid
administration
 Opioid analgesics can be transferred to the fetus by maternal administration or direct
intramuscular or intra-venous umbilical cord administration using ultrasound guidance
 For most invasive procedures that can cause noxious fetal stimulation, fetal
intramuscular administra-tion of fentanyl 10 to 20 μg/kg (or other opioid in equiv-alent
dosing) is used to provide analgesia immediately before the intervention
 can be achieved per-cutaneously using ultrasound guidance or under direct vision
when a hysterotomy is performed.
 Some physicians administer prophylactic intramuscular atropine 20 μg/kg with opioids
to minimize the risk for fetal brady-cardia.
Anesthetic goals include
 prevention of fetal movement
 inhibition of circulatory stress response,
 adequate pain relief, and
 potentially even fetal amnesia.
 Prevention of fetal movement: During IUT, the transfusion needle can lacerate
umbilical vessels with unanticipated fetal movement, and use of laser therapy for
TTTS can disrupt surface placental vessels critical to fetal blood flow.
 fetal movement can be prevented by intramuscular or umbilical vessel
administration of muscle relaxant using ultrasound guidance.
 Drugs that have been used include pancuronium or vecuronium with doses of 0.3
mg/kg intramuscularly or 0.1 to 0.25 mg/kg intravenously.
 The onset of fetal paralysis varies with the specific drug and dose, but typically
occurs in 2 to 5 minutes, with an approximate duration of 1 to 2 hours
 For open fetal procedures, placental transfer of maternally administered general
anesthesia with volatile anesthetics provides fetal anesthesia.
 These anesthetics readily transfer across the placenta, with fetal concentration and
the fetal-to-maternal (F/M) ratio depending on both the maternal inspired
anesthetic concentration and the duration of maternal anesthetic administration.
 Nitrous oxide has an F/M ratio of 0.83 after only 3 minutes of administration
 High levels of volatile anesthetic can depress fetal myocardium and lead to
increasing fetal acidosis
 epileptiform EEG activityand generalized tonic-clonic seizures in both adults
andchildren exposed to high levels of sevoflurane
 Therefore, high concentrations of volatile anesthetic administration, useful for
maternal uterine relaxation, might not be the optimal anesthetic for the fetus
despite years of successful use.
 Remifentanyl
 has significant placental transfer and
 Some prefer to administer maternal remifentanil and nitroglycerin as part of the
anesthetic for open fetal or EXIT procedures to decrease the amount of volatile
anesthetic.
 prevents fetal movement during TTTS laser photocoagulation therapy.
 Maternal administration and placental transfer of intravenous remifentanil provides
adequate fetal immobility during fetoscopic interventions that involve only the
umbilical cord or placenta
 For most FIGS-IT procedures- use of monitored anesthetic care with infiltration of
local anesthetic into the abdominal wall -an adequate level of maternal comfort
 Administration of additional opioid, benzodiazepine, or other anesthetic can be
used for maternal analgesia and anxiolysis, titrated to avoid deep sedation and the
associated increased risk for pulmonary aspiration of gastric contents
 Local anesthetic infiltration can be used for fetoscopic procedures, which typically
employ endoscope trocars that are only 1 to 5 mm in diameter.
 General anesthesia - rarely necessary for percutaneous procedures unless
placental location and fetal orientation present potential
technical difficulty or
uterine exteriorization is needed.

 Neuraxial techniques -when multiple insertion sites are required-

, maternal immobility must be ensured
a mini-laparotomy must be performed, or
concern exists about adequate patient comfort or
appropriate patient cooperation during the procedure.
 In cases of IUT, cord blood sampling, or thoracic shunt placement, fetal movement
may displace the needle or catheter and result in trauma, bleeding, or compromise
of the umbilical circulation.
 Although maternally administered opioids and benzodiazepines can reduce fetal
motion,they do not guarantee immobility for procedures directly involving the
fetus.
 Fetal immobility can be safely achieved with direct fetal intramuscular or umbilical
venous administration of muscle relaxant
 General anesthesia is primarily employed for fetal surgery requiring a hysterotomy.
Unlike minimally invasive fetal procedures, open fetal surgery
1. requires profound uterine relaxation
2. often entails additional fetal monitoring beyond intermittent ultrasonography
3. involves more fetal surgical stimulation, fetal hemodynamic perturbation, and risk
for fetal compromise; and
4. requires direct administration of some drugs to the fetus.
The anesthesiologist and other team members should be prepared for significant
maternal and fetal blood loss, and the need for maternal and fetal resuscitation,
including emergent delivery.
A volatile anesthetic is commonly administered to provide maternal
and fetal anesthesia, as well as uterine relaxation, which may require a concentration
of more than 2 MAC.
 Single, weight-based, unit doses of medications for fetal analgesia and muscle
relaxation should be available for administration by the surgical team.

In addition, resuscitation medications (atropine 20 μg/kg, epinephrine 10 μg/kg,

and crystalloid 10 mL/kg) should be prepared preoperatively for immediate
availability in the emergent treatment of intraoperative fetal hemodynamic
compromise.

Drugs and approaches should be used to minimize aspiration of gastric contents

. Uterine tocolytics (i.e., indomethacin) should be given to the mother preoperatively.
 An epidural catheter is placed preoperatively for administration of postoperative
analgesia.
 FHR is assessed and baseline cardiac echocardiography and ultrasound imaging
of umbilical cord flow characteristics are performed before anesthetic induction
and are intermittently reevaluated throughout the initial period of anesthetic
administration to assess the effect on the fetus of the maternal positioning,
anesthetic administration, and any maternal hemodynamic changes.
 After anesthetic induction and before maternal skin incision, conventional
concentrations of anesthetics are administered to the mother (∼1 MAC); ventilation
is controlled to maintain eucapnia (end-tidal CO2 [ETCO2] levels of 30 to 32 mm
Hg); and fetal attitude, presentation, and placental location are reassessed by
ultrasound.
 An invasive maternal intraarterial pressure catheter is placed when administration
of a nitroglycerin infusion is planned for uterine tocolysis.

Intravenous fluids administered to the mother are minimized (<2 L) to decrease the
risk for perioperative pulmonary edema associated with the use of tocolytics, such
as magnesium sulfate or administration of large doses of nitroglycerine during
fetal surgery.

Typical maternal hemodynamic goals include maintaining systolic arterial blood

pressure within 10% of baseline values and mean arterial pressure greater than 65
mm Hg.
 Administration of a maternal nondepolarizing muscle relaxant is usually
unnecessary with administration of appropriate concentrations of volatile
anesthetics, but may be used to improve operative conditions.

If it is used, appropriate neuromuscular monitoring should be employed to

carefully assess neuromuscular function with appropriate pharmacologic reversal
of blockade before tracheal extubation, particularly with concurrent use of
magnesium sulfate, which significantly potentiates neuromuscular blockade
 Before skin incision, the inspired concentration of volatile anesthetic is increased,
and before uterine incision, the volatile anesthetic end-tidal concentration is
further increased (≥2 MAC) to provide profound uterine relaxation.

If uterine relaxation is assessed to be inadequate by appearance of contractions or

palpation, administration of additional volatile agent (up to 3 MAC) or intravenous
nitroglycerin as an infusion or in small boluses (50 to 200 μg) is useful to decrease
uterine tone.
 Use of nitroglycerin may affect fetal vascular tone, resulting in alterations in
cerebral blood flow and increased likelihood of fetal cerebral ischemia, as well as
intraventricular and periventricular hemorrhage
 Periodic ultrasonography is used to assess FHR and fetal cardiac function. In some
open fetal procedures, pulse oximetry or additional direct fetal monitoring can be
employed after the hysterotomy is performed,

Rarely, when uncertainty exists regarding fetal condition, umbilical cord blood gas
measurements can be obtained.

an opioid and a muscle relaxant can be administered to the fetus intramuscularly

either before uterine incision with ultrasound guidance of the injection needle or
under direct vision after uterine incision.

Intramuscular atropine also can be administered concurrently to reduce opioid-

induced fetal bradycardia.
 After uterine exposure and ultrasound placental mapping, a small hysterotomy is
created away from the placenta.

Uterine blood loss can be rapid and difficult to estimate. Vigilant observation of the
surgical field and careful maternal monitoring are essential to avoid missing occult
hemorrhage.

Lost amniotic fluid is replaced with warmed crystalloid to bathe the exposed fetus.

Intrauterine temperature is closely monitored to prevent hypothermia and

associated fetal circulatory compromise.
 For fetal mass resections or other open procedures with high risk for significant
fetal blood loss, an intravenous catheter should be placed in a fetal limb for blood
and fluid transfusions.

All blood or fluids transfused to the fetus should be warmed. In urgent situations,
fluids can be transfused directly into the umbilical vein through catheter access
obtained in the operative field if a fetal peripheral intravenous line is not available.
 In the rare event of maternal hemodynamic collapse, if maternal resuscitation has
been unsuccessful in restoring adequate maternal hemodynamics after 4 minutes,
the fetus should be delivered emergently to relieve aortocaval compression,
improve maternal resuscitation efforts, and increase the chance for maternal
survival.
 After completion of the fetal procedure, an initial dose of magnesium sulfate 4 to 6
g intravenously over 20 minutes is typically administered during uterine closure to
reduce myometrial contractility

After the bolus, an intravenous infusion of magnesium sulfate 1 to 2 g/hr) is

initiated to maintain uterine quiescence into the postoperative period. The inspired
concentration of volatile anesthetic or intravenous nitroglycerin infusion is
significantly decreased or discontinued after the magnesium sulfate bolus is
complete.
 Maternal anesthesia is maintained with epidural anesthesia, supplemented by
administration of intravenous opioid, inhaled N2O, and/or intravenous propofol;
this allows adequate time for elimination of the volatile agents during surgical
closure of the abdominal incision.

The mother’s trachea is extubated after she awakens and after confirming adequate
neuromuscular recovery and hemodynamic stability.
 In addition to postoperative concerns associated with a cesarean delivery (i.e.,
pain management, prevention of venous thromboembolism, monitoring for
hemorrhage, avoiding wound infection), postoperative care of patients undergoing
fetal surgery also focuses on tocolysis and fetal monitoring.

For minimally invasive procedures such as cordocentesis or IUT, tocolysis is

typically not required. For more invasive percutaneous procedures (e.g., shunt
catheter placement, endoscopic techniques),
 some fetal surgery teams administer preoperative prophylactic tocolytic agents
such as indomethacin, and rarely additional drugs are required in the
postoperative period.
 After open fetal surgery, patients frequently experience early uterine contractions
and require continuous uterine monitoring for 2 or 3 days.
Management of postoperative preterm labor after fetal surgery is a challenge and
has led to significant fetal morbidity.
Magnesium sulfate infusions initiated intraoperatively are continued for
approximately 24 hours or more postoperatively.
Additional tocolytic agents (e.g., indomethacin, terbutaline, nifedipine) are often
necessary.
 Administration of indomethacin requires periodic monitoring by fetal
echocardiography because premature closure of the ductus arteriosus is a known
complication of therapy.
 The fetus is evaluated postoperatively by ultrasonography

Continuous FHR monitoring is used in the postoperative period, with a

predetermined plan established for management of fetal distress.
The duration of monitoring is based on gestational age, fetal condition, and plan for
fetal distress.
 Potential fetal morbidity includes infection, fetal heart failure, fetal intracranial
hemorrhage, and fetal demise. If maternal pulmonary edema is suspected, a chest
radiograph should be obtained.
 With significant compromise, critical care admission may be required along with
tracheal intubation, mechanical ventilation, hemodynamic monitoring,
supplemental oxygen administration, upright positioning, and diuretic therapies.

For minimally invasive procedures, satisfactory postoperative analgesia is typically

achieved by administration of oral opioid-based pain medications.

For open procedures, postoperative epidural analgesia can be provided for several
days using a dilute solution of local anesthetic and opioid.
 Intravenous opioids administered with a patient-controlled device can be used in
place of an epidural or after the epidural is discontinued. Use of opioids can
decrease FHR variability and create some difficulty in interpretation of the FHR
tracing.
 Inadequate postoperative pain control can increase plasma oxytocin levels and
increase the risk for preterm labor
After open fetal procedures, patients are at high risk for PPROM, preterm labor,
infection, and uterine rupture. In addition to these risks, periodic assessment of fetal
wellbeing, growth, and integrity of the pregnancy necessitate the mother remain near
the fetal treatment institution for the first few weeks after the procedure.
The possibility of preterm delivery may necessitate a course of steroids to improve fetal
lung maturity.
After open procedurescesarean delivery is often planned for 37 weeks gestation but
may be required earlier with the onset of preterm labor.
The recent hysterotomy increases the chance for uterine rupture and associated need
for emergent cesarean delivery.
 Conditions that compromise the fetal airway, such as large neck masses, congenital
high airway obstruction, or severe micrognathia
 The EXIT procedure allows the fetus to remain supported by the placental unit with
adequate oxygenation and perfusion while surgical repair and resuscitation
interventions are performed in a controlled manner.
 The procedure has been used successfully to treat fetuses requiring intrathoracic
mass resection, in separation of conjoined twins, and as a bridge to extracorporeal
support.
 The primary goals of the EXIT procedure are to main-tain a prolonged state of
uterine relaxation, to delay placental separation, and to sustain placental-fetal
perfusion
 Frequently performed under general anesthesia, employing high concentrations
(≥2 MAC) of volatile anesthetic to ensure uterine relaxation.
 Neuraxial anesthesia in combination with remifentanil, nitroglycerin, or both also
has been used successfully
 The overall preoperative and intraoperative approach for anesthetic management
is similar to that previously described for open fetal surgery
 The primary difference occurs after delivery of the fetus, when uterine relaxation
is no longer required
 Thus, after delivery of the neonate, anesthetic management becomes similar to
management of a cesarean delivery with general anesthesia.
 Fetal anesthesia from transplacental transfer of maternal volatile anesthetic can be
supplemented by fetal intramuscular administration of an opioid (e.g., fentanyl 5 to
15 μg/kg or morphine 0.1 mg/kg, depending on the indication) and a paralytic
agent (rocuronium 1 to 3 mg/kg or pancuronium 0.1 to 0.3 mg/kg).

Sometimes intramuscular atropine μg/kg) is given to prevent fetal bradycardia.

 After assessment of appropriate uterine relaxation, the placental border is
determined by ultrasonography.

A small initial hysterotomy is extended outside the placental border with a stapling
device to prevent excessive blood loss.

If the EXIT procedure is performed to facilitate fetal intubation or neck mass

resection, only the fetal head and shoulders are initially delivered

For ore extensive procedures requiring access to the thorax or other anatomic
locations, the entire body may be delivered.
 Before hysterotomy, the fetus is monitored with echocardiography and
ultrasonographic evaluation of umbilical cord flow. After hysterotomy, a pulse
oximeter probe is placed on the fetal hand and shielded from ambient light.
Warmed crystalloid fluids are irrigated continuously in the uterine cavity to
maintain fetal temperature and prevent placental separation or spasm of umbilical
vessels.
Care should also be taken to avoid inadvertent compression or unnecessary
manipulation of the umbilical cord, which could lead to vascular reactivity and
decreased flow.
Depending on the indication, the duration of an EXIT procedure ranges from a few
minutes (e.g., intubation) to several hours (intrathoracic mass resection, neck mass
resection with tracheostomy, or ECMO cannulation).
 Before ventilation of the fetal lungs, fetal oxyhemoglobin saturation is typically
40% to 70%.
After initiating ventilation of the fetal lungs, oxyhemoglobin saturation should
increase significantly to above 90%.
 When fetal lung ventilation fails to result in an appropriate increase in
oxyhemoglobin saturation, this represents an indication for ECMO initiation before
clamping the umbilical cord and fetal delivery.
 An ETCO2 indicator is also beneficial in confirming correct placement of the
endotracheal tube.
If needed, pulmonary surfactant may be administered once the endotracheal tube
is placed.
 Transporting the neonate to the intensive care area for further care requires significant
vigilance to ensure the critical, tentative airway remains secured.
Once the fetus is delivered, the inspired concentration of the volatile agent is
significantly decreased, the nitroglycerin infusion stopped, or both to allow the uterus
to contract and diminish the risk for maternal hemorrhage
N2O, propofol, and/or an opioid can be administered to maintain adequate anesthesia
Oxytocin is routinely administered and additional uterotonic drugs are given when
necessary
Once the patient is hemodynamically stable with appropriate uterine tone, epidural
analgesia may be initiated.
 Tocolysis is essential during fetal surgery and after operation as fetal interventions are
associated with preterm labour.
 Impaired uterine blood flow or partial placental separation can occur due to uterine
manipulation or incisions, hence jeopardizing umbilical–placental blood flow
 Even minor interventions (e.g. needle insertion for intrauterine transfusion) can result
in strong uterine contractions, and hence may cause unintentional puncture of other
structures
 Tocolysis is also important after operation as preterm uterine contractions can still
occur.
 Almost all drugs will eventually cross the placenta to reach the fetus.In some cases,
this transplacental transfer may be beneficial anddrugs may be deliberately
administered to the mother in order to treat specific fetal conditions. For example,
steroids may be given to the mother to promote fetal lung maturation and cardiac
drugs maybe given to control fetal arrhythmias.
 However, the transplacental passage of drugs may also have detrimental effects on
the fetus, including teratogenicity or impairmentof fetal growth and development.
The greatest risk of adverse drugeffects on the fetus is probably during
organogenesis which takesplace in the first trimester.
 The effects of drugs on the fetus may be either direct or may be mediated via the
alteration of uteroplacental blood flow.
 Three types of drug transfer across the placenta are recognized
(i) Complete transfer (type 1 drugs): for example, thiopental. Drugs exhibiting this
type of transfer will rapidly cross the placenta with pharmacologically
significant concentrations equilibrating in maternal and fetal blood.
(ii) Exceeding transfer (type 2 drugs): for example, ketamine. These drugs cross the
placenta to reach greater concentrations in fetal compared with maternal blood.
(iii) Incomplete transfer (type 3 drugs): for example, succinylcholineThese drugs
are unable to cross the placenta completely,resulting in higher concentrations in
maternal compared with fetal blood.
 Drugs which transfer from the maternal to the fetal blood must be carried into the
intervillous space and pass through the syncytiotrophoblast, fetal connective tissue,
and the endothelium of fetal capillaries.

The rate-limiting barrier for placental drug transfer is the layer of

syncytiotrophoblast cells covering the villi.
Decrease transplacental transfer
There are four main
mechanisms of drug transfer
across the placenta

A, simple diffusion
B, facilitated diffusion using a
carrier
C, active transport using ATP
D, pinocytosis
 Simple diffusion: e.g. midazolam and paracetamol

Most drugs (especially type 1 drugs) cross the placenta by this mechanism.
 Transfer is either transcellularly through the syncytio
trophoblast layer or paracellularly through water channels incorpo
rated into the membrane.
Diffusion does not require energyinput but is dependent on a concentration gradient
across theplacenta with drug passively moving from areas of high to lowconcentration.
The transfer of drugs which passively diffuse from mother tofetus is governed by Fick’s
law of diffusion.3
This states that the rateof diffusion per unit time is directly proportional to the surface
areaof the membrane (placenta) and the concentration gradient across it,and inversely
proportional to the thickness of the membrane:
Q is the rate of drug diffusion
across the placenta per unit time

k the diffusion constant

SA the surface area of placental

Membrane

C1 the maternal concentration of

free drug

C2 the fetal concentration of free

drug,

d the thickness of placental mem-

brane.
 In the normal placenta, the villous surface area and blood flow tothe placenta
increase with gestation.
 The placental membranes alsothin out and the cytotrophoblast layer almost
completely disappears.
 These changes increase the passive diffusion of drugs and nutrientsto the growing
fetus.

Infective processes affecting the placenta may result in an increase in the thickness
of placental membranes whichwill reduce passive diffusion across them
Facilitated diffusion: e.g. cephalosporins and glucocorticoids

Drugs structurally related to endogenous compounds are often trans

ported by facilitated diffusion. This type of transport needs a carrier
substance within the placenta to facilitate transfer across it.

Again,energy input is not required since drug transfer occurs down a concentration
gradient. Facilitated diffusion will be inhibited if the
carrier molecules become saturated by both drug and endogenous
substrates competing for their use.8
 Active transport: e.g. norepinephrine and dopamine
Active transport utilizes energy, usually in the form of ATP, to transport substances against a concentration or electrochemical
gradient.
Transport is carrier-mediated and saturable and there is competition between related molecules.
Active drug transporters are located on both the maternal and fetal sides of the placental membranes and can transport drugs
from mother to fetus and vice versa.
A wide range of active transporters has been identified within theplacenta and includes p-glycoprotein (involved in the transfer
of
drugs including digoxin, dexamethasone, cyclosporin A, and chemotherapeutic agents like vincristine and vinblastine), and the
multi
drug resistance proteins 1–3 (involved in the transfer of drugs such as methotrexate and HIV protease inhibitors)
The expression and distribution of drug transporters within the placenta may vary according to gestation.

 Pinocytosis
In pinocytosis, drugs become completely enveloped into invaginations of the membrane and are then released on the other
side of the
cell. Very little is known about this method of transfer and about the drugs which cross the placenta by this mechanism.
 Induction agents
Thiopental is the most commonly used induction agent in parturients.
It is a highly lipid-soluble weak acid which is 61% unionized at plasma pH and 75% bound to plasma albumin.
It rapidly crosses theplacenta and is quickly cleared by the neonate after delivery.
Propofol is also very lipid soluble and able to cross the placentaeasily. It has been associated with transient depression
of Apgarscores and neurobehavioural effects in the neonate.
 Inhalation agents
Volatile anaesthetic agents readily cross the placenta as they are highly lipid soluble and have low molecular weights.
A prolonged dose-delivery interval results in greater transfer and therefore a greater sedative effect on the neonate.
Nitrous oxide also crosses theplacenta rapidly. Diffusion hypoxia can occur in neonates exposed to nitrous oxide
immediately before delivery and therefore supplemental oxygen may be required.
 Neuromuscular blocking agents
Neuromuscular blocking agents are large, poorly lipid soluble, and highly ionized molecules. They cross
the placenta very slowly andpose no significant clinical problems to the neonate
 Opioids
All opioids cross the placenta in significant amounts.
Meperidine is commonly used during labour. It is 50% plasma protein-bound and crosses the placenta
readily. Maximal uptake by the fetal tissues occurs 2–3 h after a maternal i.m. dose, and this is the time
when
neonatal respiratory depression is most likely to occur.
Detrimental effects may last 72 h or more after delivery and are attributed to the prolonged half-life of
both meperidine and its metabolite, normeperidine, in the neonate.
Morphine is less lipid soluble but because of its poor protein binding, it readily crosses the placenta.
Fentanyl is very lipid soluble and crosses the placenta rapidly. Remifentanilcrosses the placenta but is
rapidly metabolized by the fetus and its use for labour analgesia has not been associated with adverse
neonatal effects.
 Local anaesthetic agents

In order for local anaesthetic agents administered epidurally to affectthe fetus, they
must be absorbed into the systemic circulation before placental transfer.
Local anaesthetics are weak bases and have relatively low degrees of ionization at
physiological pH. Bupivacaine andropivacaine are highly lipid soluble but have a high
degree of proteinbinding. Some systemic absorption occurs through the large
epiduralvenous plexuses with subsequent transfer across the placenta bysimple
diffusion.
Lidocaine is less lipid soluble than bupivacainebut has a lower degree of protein
binding, so it will also cross the placenta.
Local anaesthetics can accumulate in the fetus due to ‘ion trapping’ if the fetus becomes
acidotic. Ion trapping occurs when thedecreased pH in the fetus produces an increased
proportion of ionized drug which is then unable to cross the placenta
 Anticholinergics
Transfer of anticholinergic drugs across the placenta mimics the trans
fer of these drugs across the blood–brain barrier.
Glycopyrrolate is a quaternary ammonium compound which is fully ionized and is therefore poorly
transferred across the placenta.
Atropine is a lipid-soluble tertiary amine which demonstrates complete placental transfer.15
Neostigmine
Neostigmine is a quaternary ammonium compound but is a small molecule which is able to cross the
placenta more rapidly than glycopyrrolate.
In a few cases where neostigmine has been used with glycopyrrolate to reverse non-depolarizing
neuromuscular block in pregnancy, profound fetal bradycardia has been reported.13,15
Consequently, for general anaesthesia in pregnancy where the baby
is to remain in utero, it may be advisable to use neostigmine with
atropine rather than with glycopyrrolate.
 Benzodiazepines
Benzodiazepines are highly lipid soluble and unionized and therefore exhibit rapid and complete diffusion across the placenta
.
 Vasoactive drugs
Sympathomimetics such as ephedrine and phenylephrine are com
monly used to treat maternal hypotension during regional anaesthe
sia.
Ephedrine increases maternal arterial pressure mainly by increasing cardiac output via cardiac b-1 receptors, with a smaller
contribution from vasoconstriction via a-1 receptor stimulation.
It has minimal effects on uteroplacental blood flow. It readily crosses
the placenta and has been shown to be associated with a decrease inumbilical arterial pH, probably through stimulating an
increase in fetal metabolic rate.
Phenylephrine increases maternal arterial pressure by vasoconstriction through its direct effect on a-1 receptors.
It has been shown to prevent maternal hypotension without causing
fetal acidosis, when combined with rapid crystalloid infusion imme
diately after spinal anaesthetic injection