Anesthesia for fetal surgery

1. Anesthesia for fetal surgery
Frederik De Bucka, Jan Deprestb and Marc Van de Veldea
a
Department of Anesthesiology and bDepartment of Purpose of review
Gynaecology and Obstetrics, University Clinics Leuven,
Leuven, Belgium
To look at different anesthetic approaches to different surgical techniques used in fetal
procedures and the influence of maternal and fetal factors on anesthetic management.
Correspondence to Frederik De Buck, MD, Department
of Anesthesiology, University Clinics Leuven, Recent findings
Herestraat 49, B-3000 Leuven, Belgium Fetal surgery is evolving rapidly in the field of mainly ex-utero intrapartum treatment
Tel: +32 16 344270;
e-mail: frederik.debuck@uz.kuleuven.ac.be procedures, where new indications are found and new anesthetic techniques are
developed, enabling the use of locoregional anesthesia. Further development of
anesthetic techniques focuses on minimizing the risks for the mother and preserving the
Current Opinion in Anaesthesiology 2008,
21:293–297 normal neurodevelopment of the fetus.
Summary
Open fetal surgery remains a major invasive procedure for mother and fetus both,
requiring general anesthesia with adequate invasive monitoring. Minimal invasive fetal
procedures can be performed with local anesthesia alone or, for the more complex
fetoscopic procedures, with a neuraxial locoregional technique. Fetal anesthesia and
analgesia can then be provided by different routes. Ex-utero intrapartum treatment
procedures are open fetal procedures, but they can be performed with locoregional
anesthesia, when uterine relaxation can be achieved without volatile anesthetics with the
use of intravenous nitroglycerin.
Keywords
ex-utero intrapartum treatment procedures, fetal analgesia, fetal nociception, fetal
surgery, fetoscopy
Curr Opin Anaesthesiol 21:293–297
ß 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins
0952-7907
nancy [5,8,9], and most often these procedures are
Introduction performed in the second or third trimester of pregnancy.
Fetal surgery is in rapid development. With the advances
in prenatal diagnosis, many abnormalities are identified Cardiac output rises by 50–100%, both by an increase in
that may benefit from antenatal treatment. Surgical tech- heart rate and an increase in stroke volume. The blood
niques range from minimal invasive to open fetal pro- pressure drops by 15% from vasodilation and the exist-
cedures, with a trend towards less invasive fetoscopic ence of a low-resistance placental vascular bed [8].
techniques [1–3].
Intravascular blood volume increases with change in
Another rising field in fetal surgery is the ex-utero intra-
plasma composition and decrease in total protein and
partum (EXIT) surgery, also known as operations on
albumin levels. The decreased oncotic pressure leads to
placental support (OOPS). In these procedures, the fetus
an increased risk for fluid retention and pulmonary
is partially delivered and treated while the fetoplacental
edema. Decreased plasma cholinesterase levels may lead
circulation is preserved, allowing for the management of
to a prolonged effect of succinylcholine. Different drugs
fetal airways before the oxygenation from the placenta is
have changed distribution volumes, and drugs with a high
discontinued [4,5,6,7].
degree of protein binding have a larger free fraction [8,9].
Providing anesthesia for these different procedures is a
clinical challenge, in which there are always two patients Increases in different coagulation factors, such as factors
to consider, both mother and fetus. VII, VIII, IX, X and fibrinogen, cause a hypercoagulable
state, with an increased risk for thomboembolisms [8].
Maternal considerations Patients presenting for fetal surgery often have a poly-
Depending on the type of procedure, both general and hydramnios, where the second trimester uterus becomes
locoregional anesthesia can be performed. Different as large as near term in a normal pregnancy. This
changes in anatomy and physiology occur during preg- increases the risk for the supine hypotension syndrome,
0952-7907 ß 2008 Wolters Kluwer Health | Lippincott Williams Wilkins
Copyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.

2. 294 Obstetric and gynecological anesthesia
caval compression and uterine hypoperfusion due to In the postoperative phase, an adequate maternal analge-
decreased venous return. Prevention by a left lateral sia results in decreased plasma oxytocin levels and
tilted position is important in this case [5,9]. decreased uterine activity [12].
A 50% increase in minute ventilation is reflected by a
decreased normal PaCO2 of 28–32 mmHg, with a normal Fetal considerations
pH due to an increased renal excretion of bicarbonate. The fetus is at increased risk in fetal surgery due to its
The tidal volumes increase, although the respiratory rate immature organ systems. Hypothermia occurs rapidly
remains normal. Oxygen consumption increases by 20% from heat loss through the thin and easily bruised skin.
and together with a 20% decrease in functional residual It suffers easily from hypovolemia, given its low total
capacity, faster desaturation occurs should there be an blood volume, higher bleeding tendency with an imma-
airway problem. The airway mucosa is swollen and bleeds ture coagulation system, and high evaporative fluid
easily due to capillary engorgement, making pregnant losses. Hypovolemia leads to hypoperfusion, and the
patients more difficult to intubate, especially combined decreased baroreceptor activity limits the ability for
with weight gain and breast enlargement [8,9]. compensatory vasoconstriction. The decreased myo-
cardial contractility also predisposes to hypoperfusion.
The gastric acid content is elevated, with a decreased Fetal hypoperfusion, together with uteroplacental hypo-
pH due to placental gastrine secretion. The tone of the perfusion, leads to fetal hypoxia [9].
gastroesophageal sphincter is reduced secondary to hor-
monal changes and the upward shift by the gravid uterus. The issue whether or nor a fetus is capable of feeling pain
The pyloric sphincter is displaced, resulting in slower is still controversial [13], and the controversy has been
gastric emptying. It is wise to consider all pregnant renewed by the proposition of laws in different states
patients to have full stomachs, at increased risk for of the United States requiring fetal pain relief during
aspiration [5,8,9]. abortion [14]. Pain, by definition, is composed of
two systems: a physiologic reaction towards a noxious
Minimum alveolar concentration (MAC) values decrease stimulus, nociception and stress response, and an
by approximately 40%, possibly by increased levels of emotional negative perception [14].
progesterone and b-endorphin.
The autonomic and endocrine responses to noxious
The epidural space is narrowed by epidural venous stimuli, the stress response, consist of the activation of
engorgement, increasing the risk for intravascular the hypothalamic, pituitary, and adrenal axis [15]. Rises
catheter placement. There is also a larger dermatomal in blood levels of noradrenaline, cortisol and b-endorphin
spread of injected local anesthetics [8,9]. during invasive procedures in the human fetus are seen.
Alterations in the brain blood flow have been seen as early
as in the 18th week of pregnancy [15]. These autonomic
Uterine relaxation effects of noxious stimulation can be suppressed by the
For open fetal surgery and the EXIT/OOPS procedures, administration of analgesics [16].
a profound uterine relaxation is required for optimal
surgical exposure and for optimal placental gas exchange The fetal stress response to noxious stimulation does not
[4,5,6,10]. prove that the fetus has a conscious perception of pain. It
is however very unlikely that there would be pain per-
Volatile anesthetics at concentrations of minimal two ception without a stress response, so this is often used as a
MAC are very potent uterine relaxants [9]. surrogate indicator for fetal pain [16].
With high concentrations of volatile anesthetics, the The neural structures involved in pain processing develop
maternal cardiac output drops, leading to hypotension throughout the fetal life span, beginning very early with
and decreased uteroplacental perfusion with fetal development of peripheral receptors (seventh to ninth
hypoxia. Adequate monitoring of the maternal circulation gestational week), which are abundant by the 20th week.
permits the timely administration of vasopressors, such as The afferent system in the substantia gelatinosa of the
ephedrine or phenylephrine [5,9]. dorsal horn develops from the 10th to 13th week on, with
connections between peripheral receptors and spinal cord
As an alternative to a high concentration of volatiles, starting as early as eight weeks of gestation. Connections
short-lasting profound uterine relaxation is possible with from the dorsal horn to the thalamus begin at 14 weeks and
intravenous (i.v.) nitroglycerin. Although nitroglycerin are completed by 20 weeks. Thalamocortical connections
crosses the placenta, fetal effects seem mild because of are present from 13 weeks and are more developed by
a large placental metabolization [4,10,11]. 26–30 weeks [14].
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3. Anesthesia for fetal surgery De Buck et al. 295
Pain perception involves multilayered networks, forming products, such as opioids, cross the placenta. When the
diverse feedback and feed-forward loops. The neural mother is not under general anesthesia, an infusion of
elements in these networks are not inactive during their remifentanil provides both maternal and fetal sedation.
development, and they mature through a process of This infusion was very successful in providing fetal
plasticity that is impulse driven. Therefore pain percep- immobilization during fetoscopy [17]. Longer acting
tion in the fetus does not involve the same structures as in opioids can also be used to provide fetal analgesia by
the adult. The immature pain system is capable of maternal administration. This route of administration is
mounting behavioral responses to painful stimuli, as seen limited by the maternal side effects of the drug used.
by the movements of the fetus away from the stimulus
during fetal procedures [14]. When access to the fetus has been established, it is
possible to administer opioids, muscle relaxants, vagoly-
Pain is viewed as a homeostatic function, where the tics, or other drugs directly to the fetus i.v. through the
thalamus plays a central role, regulating the different umbilical vein or i.m. Opioids given to the fetus have a
spinal–brainstem loops. Fetal development of the slower metabolization than that in the adult and have a
thalamus occurs much earlier than the sensory cortex longer duration of action. Fentanyl , for example, can be
[14]. given in a dose of 5–20 mg/kg. Atropine, 20 mg/kg, is
frequently given to prevent bradycardic responses to
Even if the sensory cortex itself is not fully developed, stimulation of the fetus [9].
other structures in the developing brain can act as surro-
gates for it. Neurons in the subplate zone form an early
intrinsic synaptic network with inputs from the thalamus Open fetal surgery
and the neocortex. Subplate neurons serve as targets for As open fetal surgery involves a maternal laparotomy and
cortical and thalamic afferents and as pathway pioneers a hysterotomy, these procedures are mostly performed
for corticothalamic efferents. They coordinate receptive under general anesthesia [18]. After a rapid sequence
fields and are involved in gyrification. They are particu- induction (risks for aspiration), anesthesia is maintained
larly susceptible to the preterm injuries that trigger by volatile anesthetics, increasing the concentration
cognitive and sensory deficits. The subplate zone is when the uterus is incised. At least two MAC is used
active in the second-trimester human fetus [14]. for profound uterine relaxation [5]. If it is needed, i.v.
nitroglycerin can also be used for short-lasting uterine
As fetal brain development is influenced by external relaxation [4,10,11]. The use of high concentrations
stimuli, strong and recurring stimuli may result in the of volatiles and nitroglycerin often necessitates vaso-
formation of aberrant synapses, causing hyperactive pressor support for adequate uteroplacental perfusion.
responses to later stimuli. In preterm infants, repetitive Ephedrine and phenylephrine can be given in small
noxious stimulation in neonatal intensive care leads to boluses, and a drip of dopamine or dobutamine can be
increased cardiovascular responses, increased salivary started to support maternal circulation. Invasive monitor-
cortisol response and altered pain thresholds and abnor- ing of the arterial blood pressure is required, and a central
mal pain-related behavior later in childhood [14]. venous line is useful for the measurement of filling status
and the administration of inotropes or vasopressors. Care
So even if the fetus or premature newborn may not should be taken not to be too liberal with fluids, as the
perceive pain on a cortical level, he or she may still be mother is at risk for postoperative pulmonary edema.
able to process the information from nociceptive stimuli Only blood losses over 100 ml should be compensated,
and model the developing nervous system in response and maintenance fluid should be restricted to 500 ml
to pain. crystalloid [18].
Therefore, one must consider providing analgesia or For postoperative pain control, the mother benefits from
anesthesia to the fetus during a fetal surgical procedure. an epidural catheter and patient-controlled analgesia.
Ways of providing this are by transplacental passage, by Adequate postoperative pain control is necessary for
direct i.v., or i.m. administration of drugs to the fetus, or the prevention of uterine contractions and premature
by intraamniotic administration. delivery. Circulating oxytocin concentrations were lower
in an animal model of open fetal surgery when adequate
When the mother is under general inhalation anesthesia, postoperative analgesia was provided with morphine
the volatile anesthetics will pass into the fetus, with a infusions [12].
somewhat slower uptake [9]. The fetus has lower MAC
values, and the concentration of volatile anesthetics is After exposure of the fetus, fetal analgesia and muscle
generally kept high for uterine relaxation, so the fetus will relaxation, for example, fentanyl 20 mg/kg and pancuro-
be anesthetized during the procedure. Different i.v. nium or vecuronium 0.2 mg/kg can be given i.m. Fetal
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4. 296 Obstetric and gynecological anesthesia
resuscitation drugs, for example, atropine 0.2 mg/kg and When a local or locoregional technique is used, the fetus
epinephrine 1 mg/kg should also be ready for the surgeon does not get any anesthesia or analgesia. It is possible to
to administer if needed [9]. give the fetus some analgesia and sedation by adminis-
tering remifentanil i.v. to the mother. Excellent results
Perioperative fetal monitoring is possible with a sterile have been reported with this technique for the immo-
pulse oximeter or by continuous fetal echocardiography. bilization of the fetus during lasering of connecting
Fetal blood gas sampling from the umbilical artery is vessels in TTTS [17]. For more painful procedures
also possible. on the fetus, direct fetal analgesia and muscle relaxation
can be given either i.m. or through the umbilical vessels
As fetal bleeding is frequent and the fetus has a very low [20].
blood volume, fetal transfusion blood , type O negative and
leukocyte-free, should be available in aliquots of 50 ml.
Ex-utero intrapartum procedure or operations
Prophylactic tocolysis is already started preoperatively by on placental support
rectal indomethacin 50 mg, and postoperative tocolysis can The ex-utero intrapartum procedure was originally devel-
be provided, together with adequate analgesia, by mag- oped for the removing of a tracheal balloon and the
nesium sulfate, loading dose of 6 g i.v., followed by an securing of the neonatal airways before the umbilical
infusion of 3 g/h [9]. A careful monitoring of recovery of cord was cut, so that the neonate could remain oxyge-
muscular function is needed, as magnesium sulfate poten- nated by the placental circulation [5]. Recently, many
tates nondepolarizing neuromuscular blockers. Other other indications for this type of operation, on placental
tocolytic drugs that can be used postoperatively are i.v. support (OOPS), have been selected. This operation is
atosiban, oral nifedipine or subcutaneous terbutalin. now performed not only on children with a congenital
malformation that poses a problem for the airways, such
Frequent complications after open fetal surgery are pul- as large intraoral masses or cysts, cystic hygromas of the
monary edema, premature labor, amniotic fluid leak and neck or other fetal neck masses, but also on children that
fetal demise. Sometimes admission to ICU may be neces- have a congenital high airway obstruction syndrome
sary [18]. (CHAOS), so that the airway can be secured by laryngo-
scopy and intubation or tracheostomy before the
separation from the placenta [4,5,7]. Treatment of
Minimally invasive fetal surgery intrathoracic lesions with a compromised lung expansion
Minimally invasive procedures can be ultrasound-guided is also described [6,23].
needling for fetal blood sampling, intrauterine transfu-
sion, selective feticide, radiofrequency ablation of a non- The installation of an extracorporeal membrane oxyge-
viable twin [19] or fetal cardiac punction for laser atrial nator (ECMO) prior to separation from the placental
septostomy [20]. Fetoscopic procedures, intrauterine circulation (EXIT-to-ECMO procedure) allows the time
endoscopic surgery, can be performed for laser coagu- on placental support to remain short, preventing major
lation of connecting vessels in twin-to-twin transfusion maternal complications, especially bleeding. The neo-
syndrome (TTTS), selective cord occlusion, or fetal nate can then be further treated while his oxygenation is
endoscopic tracheal balloon occlusion (FETO), and for provided by the ECMO [23].
the subsequent removal of the tracheal balloon or the
resection of urethral valves [1,3,12,21]. Most frequently, these procedures are performed while
the mother is under general anesthesia, with a type of
As these procedures are less invasive for the mother, a anesthesia comparable to open fetal surgery and with
general anesthesia is not always necessary [18,19]. Many high concentrations of volatile anesthetics for uterine
of the ultrasound-guided needling procedures can be relaxation [5,7,10]. This uterine relaxation is needed
performed using local anesthesia of the maternal abdomi- for the prevention of placental separation and the
nal wall alone [20]. For most of the fetoscopic procedures, preservation of the uteroplacental circulation. As the
either a local anesthesia or a locoregional anesthesia such uteroplacental circulation is dependent on maternal
as epidural or combined spinal epidural anesthesia is used hemodynamic stability, inotropes, vasopressors or fluids
[19,21,22]. may be used for the treatment of maternal hypotension.
Invasive monitoring is highly recommended [5,7].
If a general anesthesia is necessary, the same type of
anesthesia as for an open fetal procedure can be used. Cases in which a general anesthesia is to be avoided (e.g.
High concentrations of volatile anesthetics are less for patients at risk for malignant hyperthermia [11] or
needed because the trauma to the uterus and the uterine with a known difficult airway [24]), a locoregional tech-
activity is smaller [9,21]. nique such as a combined spinal epidural anesthesia
Copyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.

5. Anesthesia for fetal surgery De Buck et al. 297
5 Kuczkowski T, Krzysztof M. Advances in obstetric anesthesia: anesthesia for
(CSE) is also possible, but with the use of nitroglycerin fetal intrapartum operations on placental support. J Anesth 2007; 21:243–
i.v. to provide a rapid reversible profound uterine relaxa- 251.
tion [4,6,10,11,24]. Recent review of the anesthetic approach for EXIT/OOPS procedures.
The author works at the University of California, San Diego, a center that
pioneered and has gained a large experience with these and other fetal inter-
ventions.
One of the major maternal complications after an EXIT
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Case series and thorough discussion about the EXIT procedure for intrathoracic
during lengthy procedures. Postoperative blood loss is fetal lesions, requiring more or less invasive neonatal interventions.
correlated with uterine atony, possibly from prolonged 7 Marwan A, Crombleholme TM. The EXIT procedure: principles, pitfalls, and
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9 Myers LB, Cohen D, Galinkin J, et al. Anaesthesia for fetal surgery. Paediatr
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This study shows that EXIT/OOPS procedures can be performed under LRA with
Fetal anesthesia is achieved either by transplacental the use of nitroglycerin for uterine relaxation.
administration when the mother is under general 11 Rosen MA, Andreae MH, Cameron AG. Nitroglycerin for fetal surgery:
anesthesia or by direct fetal i.v. or i.m. administration fetoscopy and ex utero intrapartum treatment procedure with malignant
hyperthermia precautions. Anesth Analg 2003; 96:698–700.
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Conclusion
13 Lee SJ, Peter Ralston HJ, Drey EA, et al. Fetal pain: a systematic
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these patients have their specific needs and special Up-to-date overview of the evidence about fetal pain/nociception and its long-term
considerations for anesthesia. The pregnant mother, with effects. This article puts the political and ethical debate around the issue of fetal
pain in a more scientific perspective, focusing also on the long-term effects of fetal
all the changes in physiology caused by pregnancy, is at nociceptive stimulation.
increased overall risk when she needs to undergo a 15 Rychik J, Tian Z, Cohen MS, et al. Acute cardiovascular effects of fetal surgery
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Copyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.