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Anesthesia for fetal surgery

Frederik De Bucka, Jan Deprestb and Marc Van de Veldea

aDepartment of Anesthesiology and bDepartment ofGynaecology and Obstetrics, University Clinics Leuven,Leuven, Belgium

Correspondence to Frederik De Buck, MD, Departmentof Anesthesiology, University Clinics Leuven,Herestraat 49, B-3000 Leuven, BelgiumTel: +32 16 344270;e-mail: frederik.debuck@uz.kuleuven.ac.be

Current Opinion in Anaesthesiology 2008,21:293–297

Purpose of review

To look at different anesthetic approaches to different surgical techniques used in feta

procedures and the influence of maternal and fetal factors on anesthetic management

Recent findings

Fetal surgery is evolving rapidly in the field of mainly ex-utero intrapartum treatment

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

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 feta

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� 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins0952-7907

IntroductionFetal surgery is in rapid development. With the advances

in prenatal diagnosis, many abnormalities are identified

that may benefit from antenatal treatment. Surgical tech-

niques range from minimal invasive to open fetal pro-

cedures, with a trend towards less invasive fetoscopic

techniques [1–3].

Another rising field in fetal surgery is the ex-utero intra-

partum (EXIT) surgery, also known as operations on

placental support (OOPS). In these procedures, the fetus

is partially delivered and treated while the fetoplacental

circulation is preserved, allowing for the management of

fetal airways before the oxygenation from the placenta is

discontinued [4�,5��,6��,7].

Providing anesthesia for these different procedures is a

clinical challenge, in which there are always two patients

to consider, both mother and fetus.

Maternal considerationsDepending on the type of procedure, both general and

locoregional anesthesia can be performed. Different

changes in anatomy and physiology occur during preg-

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0952-7907 � 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins

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nancy [5��,8,9], and most often these procedures are

performed in the second or third trimester of pregnancy.

Cardiac output rises by 50–100%, both by an increase in

heart rate and an increase in stroke volume. The blood

pressure drops by 15% from vasodilation and the exist-

ence of a low-resistance placental vascular bed [8].

Intravascular blood volume increases with change in

plasma composition and decrease in total protein and

albumin levels. The decreased oncotic pressure leads to

an increased risk for fluid retention and pulmonary

edema. Decreased plasma cholinesterase levels may lead

to a prolonged effect of succinylcholine. Different drugs

have changed distribution volumes, and drugs with a high

degree of protein binding have a larger free fraction [8,9].

Increases in different coagulation factors, such as factors

VII, VIII, IX, X and fibrinogen, cause a hypercoagulable

state, with an increased risk for thomboembolisms [8].

Patients presenting for fetal surgery often have a poly-

hydramnios, where the second trimester uterus becomes

as large as near term in a normal pregnancy. This

increases the risk for the supine hypotension syndrome,

d.

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294 Obstetric and gynecological anesthesia

caval compression and uterine hypoperfusion due to

decreased venous return. Prevention by a left lateral

tilted position is important in this case [5��,9].

A 50% increase in minute ventilation is reflected by a

decreased normal PaCO2of 28–32 mmHg, with a normal

pH due to an increased renal excretion of bicarbonate.

The tidal volumes increase, although the respiratory rate

remains normal. Oxygen consumption increases by 20%

and together with a 20% decrease in functional residual

capacity, faster desaturation occurs should there be an

airway problem. The airway mucosa is swollen and bleeds

easily due to capillary engorgement, making pregnant

patients more difficult to intubate, especially combined

with weight gain and breast enlargement [8,9].

The gastric acid content is elevated, with a decreased

pH due to placental gastrine secretion. The tone of the

gastroesophageal sphincter is reduced secondary to hor-

monal changes and the upward shift by the gravid uterus.

The pyloric sphincter is displaced, resulting in slower

gastric emptying. It is wise to consider all pregnant

patients to have full stomachs, at increased risk for

aspiration [5��,8,9].

Minimum alveolar concentration (MAC) values decrease

by approximately 40%, possibly by increased levels of

progesterone and b-endorphin.

The epidural space is narrowed by epidural venous

engorgement, increasing the risk for intravascular

catheter placement. There is also a larger dermatomal

spread of injected local anesthetics [8,9].

Uterine relaxationFor open fetal surgery and the EXIT/OOPS procedures,

a profound uterine relaxation is required for optimal

surgical exposure and for optimal placental gas exchange

[4�,5��,6��,10�].

Volatile anesthetics at concentrations of minimal two

MAC are very potent uterine relaxants [9].

With high concentrations of volatile anesthetics, the

maternal cardiac output drops, leading to hypotension

and decreased uteroplacental perfusion with fetal

hypoxia. Adequate monitoring of the maternal circulation

permits the timely administration of vasopressors, such as

ephedrine or phenylephrine [5��,9].

As an alternative to a high concentration of volatiles,

short-lasting profound uterine relaxation is possible with

intravenous (i.v.) nitroglycerin. Although nitroglycerin

crosses the placenta, fetal effects seem mild because of

a large placental metabolization [4�,10�,11].

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In the postoperative phase, an adequate maternal analge-

sia results in decreased plasma oxytocin levels and

decreased uterine activity [12].

Fetal considerationsThe fetus is at increased risk in fetal surgery due to its

immature organ systems. Hypothermia occurs rapidly

from heat loss through the thin and easily bruised skin.

It suffers easily from hypovolemia, given its low total

blood volume, higher bleeding tendency with an imma-

ture coagulation system, and high evaporative fluid

losses. Hypovolemia leads to hypoperfusion, and the

decreased baroreceptor activity limits the ability for

compensatory vasoconstriction. The decreased myo-

cardial contractility also predisposes to hypoperfusion.

Fetal hypoperfusion, together with uteroplacental hypo-

perfusion, leads to fetal hypoxia [9].

The issue whether or nor a fetus is capable of feeling pain

is still controversial [13], and the controversy has been

renewed by the proposition of laws in different states

of the United States requiring fetal pain relief during

abortion [14��]. Pain, by definition, is composed of

two systems: a physiologic reaction towards a noxious

stimulus, nociception and stress response, and an

emotional negative perception [14��].

The autonomic and endocrine responses to noxious

stimuli, the stress response, consist of the activation of

the hypothalamic, pituitary, and adrenal axis [15]. Rises

in blood levels of noradrenaline, cortisol and b-endorphin

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

effects of noxious stimulation can be suppressed by the

administration of analgesics [16].

The fetal stress response to noxious stimulation does not

prove that the fetus has a conscious perception of pain. It

is however very unlikely that there would be pain per-

ception without a stress response, so this is often used as a

surrogate indicator for fetal pain [16].

The neural structures involved in pain processing develop

throughout the fetal life span, beginning very early with

development of peripheral receptors (seventh to ninth

gestational week), which are abundant by the 20th week.

The afferent system in the substantia gelatinosa of the

dorsal horn develops from the 10th to 13th week on, with

connections between peripheral receptors and spinal cord

starting as early as eight weeks of gestation. Connections

from the dorsal horn to the thalamus begin at 14 weeks and

are completed by 20 weeks. Thalamocortical connections

are present from 13 weeks and are more developed by

26–30 weeks [14��].

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Anesthesia for fetal surgery De Buck et al. 295

Pain perception involves multilayered networks, forming

diverse feedback and feed-forward loops. The neural

elements in these networks are not inactive during their

development, and they mature through a process of

plasticity that is impulse driven. Therefore pain percep-

tion in the fetus does not involve the same structures as in

the adult. The immature pain system is capable of

mounting behavioral responses to painful stimuli, as seen

by the movements of the fetus away from the stimulus

during fetal procedures [14��].

Pain is viewed as a homeostatic function, where the

thalamus plays a central role, regulating the different

spinal–brainstem loops. Fetal development of the

thalamus occurs much earlier than the sensory cortex

[14��].

Even if the sensory cortex itself is not fully developed,

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

and the neocortex. Subplate neurons serve as targets for

cortical and thalamic afferents and as pathway pioneers

for corticothalamic efferents. They coordinate receptive

fields and are involved in gyrification. They are particu-

larly susceptible to the preterm injuries that trigger

cognitive and sensory deficits. The subplate zone is

active in the second-trimester human fetus [14��].

As fetal brain development is influenced by external

stimuli, strong and recurring stimuli may result in the

formation of aberrant synapses, causing hyperactive

responses to later stimuli. In preterm infants, repetitive

noxious stimulation in neonatal intensive care leads to

increased cardiovascular responses, increased salivary

cortisol response and altered pain thresholds and abnor-

mal pain-related behavior later in childhood [14��].

So even if the fetus or premature newborn may not

perceive pain on a cortical level, he or she may still be

able to process the information from nociceptive stimuli

and model the developing nervous system in response

to pain.

Therefore, one must consider providing analgesia or

anesthesia to the fetus during a fetal surgical procedure.

Ways of providing this are by transplacental passage, by

direct i.v., or i.m. administration of drugs to the fetus, or

by intraamniotic administration.

When the mother is under general inhalation anesthesia,

the volatile anesthetics will pass into the fetus, with a

somewhat slower uptake [9]. The fetus has lower MAC

values, and the concentration of volatile anesthetics is

generally kept high for uterine relaxation, so the fetus will

be anesthetized during the procedure. Different i.v.

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products, such as opioids, cross the placenta. When the

mother is not under general anesthesia, an infusion of

remifentanil provides both maternal and fetal sedation.

This infusion was very successful in providing fetal

immobilization during fetoscopy [17]. Longer acting

opioids can also be used to provide fetal analgesia by

maternal administration. This route of administration is

limited by the maternal side effects of the drug used.

When access to the fetus has been established, it is

possible to administer opioids, muscle relaxants, vagoly-

tics, or other drugs directly to the fetus i.v. through the

umbilical vein or i.m. Opioids given to the fetus have a

slower metabolization than that in the adult and have a

longer duration of action. Fentanyl , for example, can be

given in a dose of 5–20 mg/kg. Atropine, 20 mg/kg, is

frequently given to prevent bradycardic responses to

stimulation of the fetus [9].

Open fetal surgeryAs open fetal surgery involves a maternal laparotomy and

a hysterotomy, these procedures are mostly performed

under general anesthesia [18]. After a rapid sequence

induction (risks for aspiration), anesthesia is maintained

by volatile anesthetics, increasing the concentration

when the uterus is incised. At least two MAC is used

for profound uterine relaxation [5��]. If it is needed, i.v.

nitroglycerin can also be used for short-lasting uterine

relaxation [4�,10�,11]. The use of high concentrations

of volatiles and nitroglycerin often necessitates vaso-

pressor support for adequate uteroplacental perfusion.

Ephedrine and phenylephrine can be given in small

boluses, and a drip of dopamine or dobutamine can be

started to support maternal circulation. Invasive monitor-

ing of the arterial blood pressure is required, and a central

venous line is useful for the measurement of filling status

and the administration of inotropes or vasopressors. Care

should be taken not to be too liberal with fluids, as the

mother is at risk for postoperative pulmonary edema.

Only blood losses over 100 ml should be compensated,

and maintenance fluid should be restricted to 500 ml

crystalloid [18].

For postoperative pain control, the mother benefits from

an epidural catheter and patient-controlled analgesia.

Adequate postoperative pain control is necessary for

the prevention of uterine contractions and premature

delivery. Circulating oxytocin concentrations were lower

in an animal model of open fetal surgery when adequate

postoperative analgesia was provided with morphine

infusions [12].

After exposure of the fetus, fetal analgesia and muscle

relaxation, for example, fentanyl 20 mg/kg and pancuro-

nium or vecuronium 0.2 mg/kg can be given i.m. Fetal

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296 Obstetric and gynecological anesthesia

resuscitation drugs, for example, atropine 0.2 mg/kg and

epinephrine 1 mg/kg should also be ready for the surgeon

to administer if needed [9].

Perioperative fetal monitoring is possible with a sterile

pulse oximeter or by continuous fetal echocardiography.

Fetal blood gas sampling from the umbilical artery is

also possible.

As fetal bleeding is frequent and the fetus has a very low

blood volume, fetal transfusion blood , type O negative and

leukocyte-free, should be available in aliquots of 50 ml.

Prophylactic tocolysis is already started preoperatively by

rectal indomethacin 50 mg, and postoperative tocolysis can

be provided, together with adequate analgesia, by mag-

nesium sulfate, loading dose of 6 g i.v., followed by an

infusion of 3 g/h [9]. A careful monitoring of recovery of

muscular function is needed, as magnesium sulfate poten-

tates nondepolarizing neuromuscular blockers. Other

tocolytic drugs that can be used postoperatively are i.v.

atosiban, oral nifedipine or subcutaneous terbutalin.

Frequent complications after open fetal surgery are pul-

monary edema, premature labor, amniotic fluid leak and

fetal demise. Sometimes admission to ICU may be neces-

sary [18].

Minimally invasive fetal surgeryMinimally invasive procedures can be ultrasound-guided

needling for fetal blood sampling, intrauterine transfu-

sion, selective feticide, radiofrequency ablation of a non-

viable twin [19�] or fetal cardiac punction for laser atrial

septostomy [20]. Fetoscopic procedures, intrauterine

endoscopic surgery, can be performed for laser coagu-

lation of connecting vessels in twin-to-twin transfusion

syndrome (TTTS), selective cord occlusion, or fetal

endoscopic tracheal balloon occlusion (FETO), and for

the subsequent removal of the tracheal balloon or the

resection of urethral valves [1,3,12,21].

As these procedures are less invasive for the mother, a

general anesthesia is not always necessary [18,19�]. Many

of the ultrasound-guided needling procedures can be

performed using local anesthesia of the maternal abdomi-

nal wall alone [20]. For most of the fetoscopic procedures,

either a local anesthesia or a locoregional anesthesia such

as epidural or combined spinal epidural anesthesia is used

[19�,21,22].

If a general anesthesia is necessary, the same type of

anesthesia as for an open fetal procedure can be used.

High concentrations of volatile anesthetics are less

needed because the trauma to the uterus and the uterine

activity is smaller [9,21].

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When a local or locoregional technique is used, the fetus

does not get any anesthesia or analgesia. It is possible to

give the fetus some analgesia and sedation by adminis-

tering remifentanil i.v. to the mother. Excellent results

have been reported with this technique for the immo-

bilization of the fetus during lasering of connecting

vessels in TTTS [17]. For more painful procedures

on the fetus, direct fetal analgesia and muscle relaxation

can be given either i.m. or through the umbilical vessels

[20].

Ex-utero intrapartum procedure or operationson placental supportThe ex-utero intrapartum procedure was originally devel-

oped for the removing of a tracheal balloon and the

securing of the neonatal airways before the umbilical

cord was cut, so that the neonate could remain oxyge-

nated by the placental circulation [5��]. Recently, many

other indications for this type of operation, on placental

support (OOPS), have been selected. This operation is

now performed not only on children with a congenital

malformation that poses a problem for the airways, such

as large intraoral masses or cysts, cystic hygromas of the

neck or other fetal neck masses, but also on children that

have a congenital high airway obstruction syndrome

(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

intrathoracic lesions with a compromised lung expansion

is also described [6��,23�].

The installation of an extracorporeal membrane oxyge-

nator (ECMO) prior to separation from the placental

circulation (EXIT-to-ECMO procedure) allows the time

on placental support to remain short, preventing major

maternal complications, especially bleeding. The neo-

nate can then be further treated while his oxygenation is

provided by the ECMO [23�].

Most frequently, these procedures are performed while

the mother is under general anesthesia, with a type of

anesthesia comparable to open fetal surgery and with

high concentrations of volatile anesthetics for uterine

relaxation [5��,7,10�]. This uterine relaxation is needed

for the prevention of placental separation and the

preservation of the uteroplacental circulation. As the

uteroplacental circulation is dependent on maternal

hemodynamic stability, inotropes, vasopressors or fluids

may be used for the treatment of maternal hypotension.

Invasive monitoring is highly recommended [5��,7].

Cases in which a general anesthesia is to be avoided (e.g.

for patients at risk for malignant hyperthermia [11] or

with a known difficult airway [24�]), a locoregional tech-

nique such as a combined spinal epidural anesthesia

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Anesthesia for fetal surgery De Buck et al. 297

(CSE) is also possible, but with the use of nitroglycerin

i.v. to provide a rapid reversible profound uterine relaxa-

tion [4�,6��,10�,11,24�].

One of the major maternal complications after an EXIT

procedure is major intraoperative and postoperative

blood loss. Intraoperative blood loss can be exaggerated

during lengthy procedures. Postoperative blood loss is

correlated with uterine atony, possibly from prolonged

effects of tocolytics [5��,6��,7,23�].

Fetal monitoring during the procedure is possible as for

open fetal surgery, with a fetal pulse oximeter, fetal

echocardiography and fetal umbilical blood sampling

for fetal blood gases and acid–base status [7].

Fetal anesthesia is achieved either by transplacental

administration when the mother is under general

anesthesia or by direct fetal i.v. or i.m. administration

of opioids and muscle relaxants [7].

ConclusionTo provide anesthesia for fetal surgery is a challenging

task. There are always at least two patients that need to

be taken care of, mother and one or more fetuses. Both

these patients have their specific needs and special

considerations for anesthesia. The pregnant mother, with

all the changes in physiology caused by pregnancy, is at

increased overall risk when she needs to undergo a

general anesthesia. In the event of maternal locoregional

or local anesthesia, the fetus is not anesthetized by

transplacental passage, so it needs special attention to

provide at least a form of analgesia. The discussion about

the existence and the nature of fetal pain is not yet

finished, but one should remain objective and choose

the anesthetic regimen that would best preserve the

normal fetal development.

References and recommended readingPapers of particular interest, published within the annual period of review, havebeen highlighted as� of special interest�� of outstanding interest

Additional references related to this topic can also be found in the CurrentWorld Literature section in this issue (pp. 414–415).

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Case report on the use of i.v. nitroglycerin and a normal concentration of volatilesfor uterine relaxation.

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�Lee H, Wagner AJ, Sy E, et al. Efficacy of radiofrequency ablation for twin-reversed arterial perfusion sequence. Am JObstet Gynecol 2007; 196:459e1–459e4.

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Case report on the use of LRA and IV nitroglycerin for an EXIT procedure in apatient with a known difficult airway.

orized reproduction of this article is prohibited.