Anesthesia For Foetal Surgery: Dr. Athira S Madhu
Anesthesia For Foetal Surgery: Dr. Athira S Madhu
Anesthesia For Foetal Surgery: Dr. Athira S Madhu
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
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,
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.
Rarely, when uncertainty exists regarding fetal condition, umbilical cord blood gas
measurements can be obtained.
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.
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
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 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).
A small initial hysterotomy is extended outside the placental border with a stapling
device to prevent excessive blood loss.
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.
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
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
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