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Fetal surgery and anaesthetic
implications
Ritu Gupta MB ChB FCARCSI
Mark Kilby MBBS MD MRCOG
Griselda Cooper OBE FRCA FRCOG
Surgery to the fetus while it is still in utero is
used to treat an increasing number of lethal and
non-lethal conditions. The problems of preterm
labour and premature rupture of membranes
associated with open surgery have led to the
development of minimal access surgical tech-
niques. Although fetal surgery is a new and fast
moving frontier of medicine, it is not one that
all obstetric anaesthetists will encounter. The
first successful human fetal operation was per-
formed in 1983, but it is still only carried out
in a limited number of specialist tertiary
centres.
The broad challenges presented to the
anaesthetist are:
(i) those related to any anaesthetic in a preg-
nant woman;
(ii) techniques used to prevent preterm labour;
(iii) maintenance of maternal homeostasis in
the face of tocolytic techniques;
(iv) maintenance of fetal homeostasis;
(v) provision of fetal analgesia during
surgery;
(vi) distance the mother may need to travel
from home.
It is expected that the indications for fetal
therapy will expand. The most frequently
occurring condition operated on relatively com-
monly in the UK is twin-to-twin transfusion
syndrome. Life-threatening conditions that have
had in utero intervention to lessen the severity
of pathology include congenital diaphragmatic
hernia, obstructive uropathy, and sacrococcy-
geal teratoma. There is also a prospective ran-
domized trial ongoing in the USA to determine
the role and efficacy of in utero surgery for
myelomeningocele.
Fetal surgical interventions include the
following.
(i) Minimally invasive ( percutaneous inser-
tion of shunts and in utero, intravascular
fetal transfusions); these are the most
commonly performed procedures.
(ii) Fetoscopic therapy.
(iii) Open procedure, involving a hysterotomy.
Intrauterine transfusions for rhesus disease and
fetal anaemia are performed by ultrasound-
directed fetal vessel puncture under local
anaesthesia. For other, more complex surgery,
the anaesthetist is part of a multidisciplinary
team which allows understanding of the patho-
genesis of the fetal conditions and how the
planned therapy may influence outcome. In this
article, it is assumed that the anaesthetist is
familiar with routine obstetric anaesthetic con-
siderations: those relevant to the fetal surgery
are highlighted.
Twin–twin transfusion
syndrome
Twin– twin transfusion syndrome (TTTS) is a
serious complication of a twin pregnancy in
which there is only one placenta (monochorio-
nic twin gestation). It complicates 10–20% of
monochorionic identical twin pregnancies.
1
It
is due to unequal blood flow across vascular
anastomoses between the two fetal circulations
with the larger twin being at risk of cardiac
overload and the smaller twin being relatively
hypoperfused. In addition to the severe haemo-
dynamic imbalance, there are discordant liquor
volumes, the ‘recipient’ twin having severe
polyhydramnios, and the ‘donor’ having severe
oligohydramnios adhering onto the uterine
wall. Both twins are therefore at risk of severe
haemodynamic compromise, death, and prema-
ture delivery. TTTS is diagnosed by ultrasound.
In addition to the fetal complications, parturi-
ents with severe TTTS may rarely develop
‘mirror syndrome’
2
which is characterized
by pulmonary oedema, anasarca (severe
generalized oedema), albuminuria, hyperten-
sion, and a reduction in haemoglobin concen-
tration due to haemodilution. The maternal
Key points
Fetal surgery is performed
in specialist centres and
requires multidisciplinary
teamwork.
In addition to obstetric
anaesthetic considerations,
the anaesthetist needs to be
conversant wit h tocolytic
methods.
Fetal analgesia is required
for some procedures.
The use of fetoscopic
procedures is increasing;
however, presently, only
laser ablation of placental
vessels is of proven efficacy.
Ritu Gupta MB ChB FCARCSI
Specialist Registrar
Department of Anaesthesia
Queen Elizabeth Hospital
Edgbaston
Birmingham B15 2TH
UK
Mark Kilby MBBS MD MRCOG
Dame Hilda Lloyd Professor of Maternal
and Fetal Medicine
Birmingham Women’s Hospital
University of Birmingham
Metchley Park Road
Edgbaston
Birmingham B15 2TG
UK
Griselda Cooper OBE FRCA FRCOG
Consultant Anaesthetist
Department of Anaesthesia
Queen Elizabeth Hospital
Edgbaston
Birmingham B15 2TH
UK
Tel: þ44 121 627 2060
Fax: þ44 121 627 2062
E-mail: gcooper@rcanae.org.uk
(for correspondence)
71
doi:10.1093/bjaceaccp/mkn004
Continuing Education in Anaesthesia, Critical Care & Pain | Volume 8 Number 2 2008
& The Board of Management and Trustees of the British Journal of Anaesthesia [2008].
All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
manifestations generally reflect the severity of the fetal placental
pathology.
Treatment options include amnioreduction (removing 1 –4 litres
of amniotic fluid from around the recipient). This is often per-
formed before 26 weeks gestation and requires serial procedures
until delivery. Although this is a relatively inexpensive simple
technique that can be performed with limited experience and pro-
vides potential rescue for both fetuses, it does not affect the under-
lying pathology. There is little improvement in the fetal condition
in advanced disease and a randomized controlled trial has shown
that pregnancies treated using this method have a greater likelihood
of survivors with cerebral palsy.
Recently, laser ablation of placental vessels has emerged as a
potential treatment for severe TTTS. It involves fetoscopic laser
photocoagulation of unidirectional arteriovenous vessels on the
surface of the twin placenta and attenuation of the haemodynamic
consequences of this pathophysiology. This technique prolongs
pregnancy compared with amnioreduction.
3
A recent systematic
review indicated that fetoscopic laser ablation was associated with
improved outcomes for fetal survival of one or both twins and
a reduced risk of long-term neurodevelopmental morbidity in sur-
vivors, see Figure 1.
Real-time ultrasound allows location of the placenta, umbilical
cord, and amniotic membranes. Technically, an anterior placental
site may be more surgically demanding. However, modification of
surgical instruments, positioning of the patient, and the creation of
an adequate ‘operating window’ using amnioinfusion all aid ade-
quate visualization of the chorionic plate and inter-twin membrane.
Risks of the procedure include: amniorrhexis ( pre-labour ruptured
amniotic membranes) 5%; subchorionic bleed (, 1%); preterm
delivery; neuromorbidity; and double or single fetal death.
Follow-up is required as there is a 5% recurrence rate.
In many centres, maternal spinal, epidural, or combined
spinal/epidural anaesthesia is used. Alternatively, local infiltration
of the skin and subcutaneous tissues with lidocaine 1% (down
to the myometrium) and maternal sedation is used. In
addition to maternal sedation, pharmacotherapy also causes fetal
immobilization. In a randomized controlled trial, Missant and
colleagues
4
demonstrated that remifentanil was a safer option
than diazepam.
Fig. 1 A systematic review of the RCT and two comparative controlled trials assessing the efficacy of fetoscopic laser ablation in the treatment of severe
TTTS
Fetal surger y and anaesthetic implications
72
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 8 Number 2 2008
Congenital diaphragmatic hernia
The incidence of congenital diaphragmatic hernia is 1:2400 live
births.
1
It causes pulmonary hypoplasia by compression of lung
tissue from the herniated organs and arguably abnormal develop-
ment of the pulmonary vasculature. Until recently, the possibilities
available to expectant parents of a fetus diagnosed with congenital
diaphragmatic hernia were termination of pregnancy or continu-
ation of the pregnancy until term with postnatal surgical correction.
A series of case cohort studies using modern fetoscopic procedures
have indicated that potentially severe congenital diaphragmatic
hernia with a high predicted risk of fatal pulmonary hypoplasia
may have improved overall survival with in utero therapy.
Recent studies have focused on ‘in utero triage’ of the fetus
emphasizing the exclusion of co-existent structural and chromoso-
mal anomalies which carry a corresponding poor prognosis. In
addition, poor lung development can be prospectively identified by
ultrasound; liver in the fetal chest; and a lung– head ratio of ,1
are relatively sensitive and specific for identifying fetuses develop-
ing pulmonary hypoplasia. Such triage has allowed the possibility
of fetal therapeutic intervention. Animal studies have indicated that
transient tracheal occlusion may prevent or lessen the structural
and physiological effects of pulmonary hypoplasia.
5
To date, two
studies have utilized lung –head ratio to establish the prospective
high risk of pulmonary hypoplasia within groups of fetuses and
compared outcome after treatment by fetoscopic tracheal occlusion
with conservative management.
In such fetoscopic procedures, combined spinal anaesthesia or
local anaesthesia is required and immobilization of the fetus is
essential.
Ex utero intrapartum treatment procedure
The ex utero intrapartum treatment (EXIT) procedure is now used
to establish a patent airway in the management of fetuses with
potential airway obstruction.
6
It allows the continuing placental
perfusion of the partially exteriorized fetus until a formal airway
has been established. Some common indications include:
(i) mass obstructing the upper airway, e.g. cystic hygroma,
thyroid goitre;
(ii) congenital high airway obstruction syndrome (CHAOS). This
spectrum of anomalies includes laryngeal web, atresia, or
cyst, and tracheal atresia or stenosis. It is characterized by
enlarged lungs, dilated distal airways, everted diaphragm,
ascites, and ultimately non-immune hydrops fetalis;
(iii) thoracic abnormalities, e.g. hydrothorax, tumours.
The EXIT procedure allows intubation, tracheostomy, or even
resection of the lesion while the infant is still on placental support.
Management requires obstetricians, anaesthetists, otolaryngolo-
gists, and paediatric surgeons. EXIT procedures are performed
during caesarean section before clamping of the umbilical cord.
When performing a hysterotomy, only the fetal head and shoulders
are delivered to preserve umbilical blood flow and to prevent eva-
porative heat and fluid loss. This allows time to secure the neonatal
airway. Continued uteroplacental circulation has been maintained
for up to 1 h without fetal compromise.
7
A potential complication
is antepartum haemorrhage at the time in which the fetal airway is
being secured due to the need for uterine relaxation.
General anaesthesia is indicated. The mother is prepared for the
eventuality of major haemorrhage with monitoring instituted
before surgery, i.e. two large bore i.v. cannulae, arterial line,
central venous line, and availability of cross-matched blood.
A rapid sequence induction with left uterine displacement (redu-
cing aorto-caval compression) is carried out with the adminis-
tration of high concentrations of volatile anaesthetic agent
(e.g. isoflurane 2– 3%) to maintain uterine relaxation. Other
tocolytics (Table 1) may be needed if there is inadequate uterine
relaxation. Vasopressor agents are required for the consequent
maternal hypotension in order to maintain uterine blood flow and
maternal well-being. Fetal anaesthesia is obtained via placental
transfer of volatile agents, but occasionally muscular paralysis may
be necessary to ensure fetal immobility.
7
Once the fetal airway has
been secured, the uterus is made to contract with an infusion of
oxytocin.
Close monitoring of uterine contraction, cardiovascular par-
ameters, and any haemorrhage is essential after the operation.
Thus, mother and baby will both require high dependency care. In
the absence of contraindications (e.g. coagulopathy), epidural
analgesia can be considered for the mother.
Table 1 Tocolytic agents
Agent Advantages Caution
b-adrenergic agents, e.g.
terbutaline, ritodrine
Maternal tachycardia,
hypotension, myocardial
ischaemia, decreased glucose
tolerance, pulmonary oedema
Magnesium sulphate In high concentration fetal
side-effects include decreased
heart rate variability, reduced
muscular activity at birth
Halogenated volatile
agents, e.g. isoflurane
Used to provide
intraoperative
relaxation
Prolonged use can cause fetal
acidosis
Glyceryl trinitrate Rapid onset of
action
Non-steroidal
anti-inflammatory
drugs, e.g.
indomethacin
Limited to short-term use for
48 h, and before gestational
age of 32 weeks, due to risk of
premature closure of ductus
arteriosus in the fetus,
decreased renal function
resulting in oligohydramnios,
increased risks of necrotising
enterocolitis and
intraventricular haemorrhage
Calcium antagonists Maternal hypotension
Fetal surger y and anaesthetic implications
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 8 Number 2 2008 73
Obstructive uropathy
Obstructive uropathy occurs in one in 1000 live births.
5
Upper
urinary tract obstruction is associated with less morbidity and mor-
tality than lower obstruction which is usually caused by posterior
urethral valves.
The obstruction increases bladder pressure, resulting in changes
in bladder structure and function, vesicoureteric reflux, hydroureter,
hydronephrosis, and a risk of chronic renal failure later in life.
1
The resulting oligohydramnios and pulmonary hypoplasia increases
neonatal mortality. Fetal surgery aims to prevent this from
occurring.
Open surgery (nephrostomy) carries a high mortality, a risk of
amniorrhexis and preterm labour, and a third of those treated still
require transplantation at a later stage. It requires maternal hyster-
otomy and has largely been abandoned. Fetal vesicoamniotic
shunting is the placement of a catheter, using a percutaneous
needle under continuous ultrasound guidance, into the fetal
bladder. The distal end of the catheter traverses the fetal anterior
abdominal wall and drains into the amniotic cavity. This procedure
is usually performed under local anaesthesia with lidocaine.
Myelomeningocele
The diagnosis of myelomeningocele is possible in early pregnancy.
It causes progressive neurological impairment and carries a poor
prognosis. Prenatal diagnosis and treatment may allow prevention
of the neurological deficit and preserve spinal cord cryoarchitecture.
Tocolysis
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. Table 1 gives examples of the
tocolytic agents which can be used and the main points about
their use. The choice of agent is determined by maternal side-
effects.
6
Drugs acting on the uterus have been reviewed
elsewhere.
8
Fetal stress
There is considerable evidence that the fetus may experience pain.
Not only is there a moral obligation to provide fetal anaesthesia
and analgesia, but it has also been shown that pain and stress may
affect fetal survival and neurodevelopment.
7
Factors suggesting
that the fetus experiences pain include the following.
(i) Neural development. Peripheral nerve receptors develop
between 7 and 20 weeks gestation, and afferent C fibres begin
development at 8 weeks and are complete by 30 weeks ges-
tation. Spinothalamic fibres (responsible for transmission of
pain) develop between 16 and 20 weeks gestation, and thala-
mocortical fibres between 17 and 24 weeks gestation.
(ii) Behavioural responses. Movement of the fetus in response to
external stimuli occurs as early as 8 weeks gestation, and
there is reaction to sound from 20 weeks gestation. Response
to painful stimuli occurs from 22 weeks gestation.
(iii) Fetal stress response. Fetal stress in response to painful
stimuli is shown by increased cortisol and b-endorphin con-
centrations, and vigorous movements and breathing efforts.
7,9
There is no correlation between maternal and fetal norepi-
nephrine levels, suggesting a lack of placental transfer of nor-
epinephrine. This independent stress response in the fetus
occurs from 18 weeks gestation.
10
There may be long-term
implications of not providing adequate fetal analgesia such as
hyperalgesia, and possibly increased morbidity and mortality.
Fetal analgesia
As with any procedure, the provision of analgesia depends on the
likely severity of pain associated with the intervention. However,
analgesia is recommended for:
(i) endoscopic, intrauterine surgery on placenta, cord, and
membranes;
(ii) late termination of pregnancy;
(iii) direct surgical trauma to the fetus.
For open surgery, where a general anaesthetic technique (with or
without an epidural) is used, the fetus obtains anaesthesia via the
placenta, although direct administration from i.m. injections can
also be used.
For fetoscopic fetal surgery, maternal anaesthesia is most
usually by local anaesthetic infiltration or a regional block. A com-
bined spinal/epidural minimizes haemodynamic changes.
These techniques can be supplemented with sedation or remi-
fentanil. Local or regional techniques are sometimes difficult
because of maternal anxiety; in addition, they may not adequately
immobilize the fetus. A mobile fetus can displace the endoscope
resulting in bleeding, fetal trauma, or compromised umbilical cir-
culation resulting in fetal death. The short-acting opioid remifenta-
nil is easy to titrate and crosses the placenta readily immobilizing
the fetus. Using a continuous infusion rate of remifentanil 0.1 mg
kg
21
min
21
, fetal immobilization and maternal sedation are
achieved.
4
Mild respiratory acidosis occurs but maternal apnoea
can be avoided and good operating conditions obtained. This tech-
nique is recommended for TTTS.
4
Fetal anaesthesia, homeostasis, and immobility can be provided
by direct fetal injections (i.m. or into the umbilical cord) with the
use of opioids, atropine, and neuromuscular blocking agents. Fetal
Fetal surger y and anaesthetic implications
74
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 8 Number 2 2008
i.m. opioids reduces the stress response.
5
Suitable anaesthetic tech-
niques for fetoscopic surgery on membranes, cord, and the pla-
centa are as discussed above.
Complications
The complications of minimal access fetal surgery are summarized
in Table 2.
Social factors
As minimal access fetal surgery is only carried out in specialist
centres, patients frequently have to travel long distances.
Organization needs to include social support for the families where
necessary. This is an important factor when considering discharge
from hospital. Good communication between the tertiary centre
and referring hospital is vital.
References
1. Danzer E, Sydorak RM, Harrison MR, Albanese CT. Review
minimal access fetal surgery. Eur J Obstet Gynaecol Reprod Biol 2003; 108:
3–13
2. Carbillon L, Oury JF, Guerin JM, Azancot A. Clinical biological features
of Ballantyne syndrome and the role of placental hydrops. Obstet Gynecol
Surv 1997; 52: 310– 4
3. Senat MV, Deprest J, Boulvain M, Paupe A, Winer N, Ville Y. Endoscopic
laser surgery versus serial amnioreduction for severe twin-to-twin trans-
fusion syndrome. New Engl J Med 2004; 351: 182– 4
4. Missant C, Van Schoubroeck D, Deprest J, Devlieger R, Teunkens A,
Van de Velde M. Remifentanil for fetal immobilisation and maternal
sedation during endoscopic treatment of twin-to-twin transfusion syn-
drome:a preliminary dose-finding study. Acta Anaesthesiol Belg 2004; 55:
239– 44
5. Fisk N, Gitau R, Teixeira J, Giannakoulopoulos X, Cameron A, Glover V.
Effect of direct fetal opioid analgesia on fetal hormonal and haemo-
dynamic stress response to intrauterine needling. Anesthesiology 2001;
95: 828 –35
6. Hirose S, Farmer DL, Lee H, Nobuhara KK. The ex utero intrapartum
treatment procedure: looking back at the EXIT. J Pediatr Surg 2004; 39:
375– 80
7. Boris P, Cox PBW, Gogarten W, Strumper D, Marcus MAE. Fetal
surgery, anaesthesiological considerations. Curr Opin Anaesthesiol 2004;
17: 235 –40
8. Eagland K, Cooper GM. Drugs acting on the uterus. Bull Royal Coll
Anaesth 2001, 10: 473– 6
9. Giannakoulopoulos X, Teixeira J, Fisk N. Human fetal and maternal nor-
adrenaline responses to invasive procedures. Pediatr Res 1999; 45:
494– 9
10. Marcus M, Gogarten W, Louwen F. Remifentanil for fetal intrauterine
microendoscopic procedures. Anesth Analg 1999; 88: S257
Please see multiple choice questions 25 –28
Table 2 Complications of minimal access fetal surgery
Complication How it can be minimized
Bleeding Avoid placenta on entering uterus
Preterm labour Use of tocolytics. Many theories used to describe why
this occurs (e.g. rapid changes in uterine volume,
infection, hormonal changes, fetomaternal stress,
and membrane rupture)
Chorioamniotic membrane
separation
Surgical technique
Premature rupture of
membranes
Most common problem associated with fetal surgery.
Research is ongoing into sealing ruptured
membranes with collagen plugs
Fetal surger y and anaesthetic implications
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 8 Number 2 2008 75
