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REVIEW

URRENT
C
OPINION

General anesthesia for caesarean section


Sarah Devroe a, Marc Van de Velde a,b, and Steffen Rex a,b

Purpose of review
For most anaesthesiologists, the clinical experience with general anaesthesia for caesarean section is very
low. General anaesthesia is mostly performed for emergency grade 1 caesarean section and due to a lack
of time to apply a neuraxial anaesthesia technique. Unfortunately, the majority of anaesthesiologists rely on
historical and partly outdated approaches in this stressful situation. We propose an evidence-based
approach to general anaesthesia for caesarean section.
Recent findings
Rapid sequence induction using propofol and rocuronium should become the standard for general
anaesthesia in the obstetric patient. Short-acting opioids are still not given routinely but should never be
withheld in case of severe preeclampsia. Cricoid pressure can only be accurately performed by trained
caregivers and should be released if intubation appears to be difficult. Supra-glottic airway devices may
safely be used in fasted, nonobese elective caesarean section, but endotracheal intubation remains the
gold standard, especially in emergency caesarean section in labouring women. Both sevoflurane and
propofol are appropriate for the maintenance of general anaesthesia during caesarean section. Awareness
remains a major concern in obstetric anaesthesia.
Summary
We present a review of recent evidence on general anaesthesia for caesarean section.
Keywords
caesarean section, general anaesthesia, propofol, rapid sequence induction, rocuronium

INTRODUCTION
Due to its rapid and predictable onset, general anaesthesia for caesarean section (CS) is nowadays virtually exclusively used in emergency situations, or
when neuraxial anaesthesia techniques have failed
or are contraindicated.
With the widespread use of neuraxial anaesthesia, the frequency of caesarean section performed under general anaesthesia has decreased
so dramatically that the routine of the individual
anaesthesiologist with this procedure becomes
insufficient. The overall effect of this phenomenon is that increasingly less anaesthesiologists feel confident with this procedure and
that often historical and outdated approaches
are applied. This is a concerning situation, as
anaesthesia is in comparison to other surgical
conditions still overrepresented as a cause of
maternal death in pregnancy: 12% of maternal
deaths could be directly or indirectly attributed to
anaesthesia [1].
In this review, we overview recent evidence and
propose a modified technique of general anaesthesia
for caesarean section.
www.co-anesthesiology.com

PREPARATION: ASPIRATION
PROPHYLAXIS AND ANTIBIOTIC
ADMINISTRATION
The publication of Mendelson [2] in 1946, in which
all obstetric patients are considered at a high risk for
pulmonary aspiration when undergoing general
anaesthesia, is so ingrained in the anaesthetic literature that most anaesthesiologists ignore that evidence has changed dramatically since then. High
risk of aspiration injury of the lungs is reported in
the presence of a high intragastric volume and a low
intragastric pH (<2.5). However, in pregnant
women, risk of aspiration may probably not be as
high as previously thought.
a
Department of Anaesthesiology, University Hospitals of the KU Leuven
and bDepartment of Cardiovascular Sciences, KU Leuven, Leuven,
Belgium

Correspondence to Sarah Devroe, Department of Anaesthesiology,


University Hospitals of the KU Leuven, Herestraat 49, 3000 Leuven,
Belgium. Tel: +32 16 34 23 12; fax: +32 16 34 42 45;
e-mail: sarah.devroe@uzleuven.be
Curr Opin Anesthesiol 2015, 28:240246
DOI:10.1097/ACO.0000000000000185
Volume 28  Number 3  June 2015

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.

General anesthesia for caesarean section Devroe et al.

RAPID SEQUENCE INDUCTION

KEY POINTS
 Propofol is now a standard induction agent for general
anaesthesia in caesarean section in healthy,
noncompromised patients.
 The combination of rocuronium and suggamadex
provides safer neuromuscular blockade than
succinylcholine.
 Remifentanil should always be used in preeclamptic
and other high-risk patients for whom marked
haemodynamic fluctuations are dangerous.
 RSI with cricoid pressure and endotracheal intubation
remains the gold standard management for general
anaesthesia in caesarean section.
 Awareness remains a major concern in obstetric
anaesthesia.

Many investigators, using different techniques,


observed normal gastric emptying in obstetric
patients [3]. The American Society of Anesthesiologists recommends in their guidelines that the elective
obstetric patient can consume clear fluids up to 2 h
before surgery, but still calls for timely aspiration
prophylaxis [4]. Regarding the intragastric pH, a
recent Cochrane analysis reported that antacids,
H2-receptor-antagonists and proton-pump antagonists significantly reduced the risk of an intragastric pH of less than 2.5, but this beneficial effect was
less consistently reported for gastric volume. When
using a single-agent prophylaxis, antacids alone were
superior to H2-antagonists, which were more effective than proton-pump inhibitors for increasing
gastric pH [5]. In some studies, the pH of gastric
aspirate was still low despite antacid prophylaxis,
what is most probably attributable to suboptimal
timing of administration [6]. Until now, we still
advise the combination of antacids and H2-receptor
antagonists, as they are relatively well tolerated, inexpensive and probably beneficial in the prevention of
aspiration pneumonitis [5]. Experience with protonpump inhibitors in obstetric anaesthesia is scarce. As
gastric emptying is normal in nonlabouring pregnant
patients and prokinetics have a less benign safety
profile, their routine use is questionable.
In an attempt to reduce the risk of maternal
infection, worldwide guidelines including those of
The National Institute for Health and Clinical
Excellence (NICE) in the UK recommend antibiotic
administration before skin incision rather than after
cord clamping [7]. Of note, this early administration
of antibiotics is only superior for the prevention of
endometritis, but not for the reduction of overall
infectious morbidity [8].

Since the seminal publication of Mendelson [2],


rapid sequence induction (RSI) is applied to all
obstetric patients, which resulted in a substantial
reduction of aspiration rates and maternal mortality
[9,10].
Recently, the 5th National Audit Project (NAP5)
in the UK reported a high incidence of intraoperative awareness in obstetric anaesthesia (1 : 670)
[11 ]. This is most probably due to the presence of
many risk factors during general anaesthesia for
caesarean section, which are listed as follows [12]:
&&

(1)
(2)
(3)
(4)
(5)
(6)
(7)

rapid sequence induction;


omission of opioids at induction;
use of low-dose thiopental;
use of muscle relaxants;
difficult airway management;
obesity;
brief period between anaesthetic induction and
start of surgery with only little time for supplementation of the intravenous (i.v.) induction
dose with propofol or a volatile agent; and
(8) high frequency of urgent surgery often performed out of working hours, resulting in
higher rates of nonconsultant care.
In addition, patients with severe preeclampsia
undergoing general anaesthesia for caesarean section are at an increased risk of stroke when compared with the use of neuraxial anaesthesia, because
the classical RSI without addition of opioids has
been associated with increased blood pressure and
neuroendocrine stress responses [1315].
Of note, the underlying disease, accompanying
circumstances and anaesthetic management have
changed dramatically since the introduction of
the RSI technique. We will therefore propose a
modified and modern approach to the RSI in obstetric patients.

Induction agents
Most textbooks still recommend a single dose of
thiopental 45 mg/kg as the induction agent of
choice for general anaesthesia in caesarean section,
arguing that this approach should result in an
acceptable depth of anaesthesia for the mother with
only limited neonatal depression. A recent survey
on the current practice in the UK showed that still
more than 90% of the responders are using thiopental for the induction of general anaesthesia in
caesarean section. In most cases, this choice was
based on historical reasons. Interestingly, 58% of
the responders would support the use of propofol for
induction [16].

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241

Obstetric and gynecological anesthesia

Propofol, in a dose sufficient for induction and


to prevent maternal awareness (2.5 mg/kg),
depresses the infant more than thiopental and
causes a reduction in maternal blood pressure
[1719]. The latter effect can be advantageous in
the hypertensive patient as compared with thiopental, propofol reduces the cardiovascular response to
laryngoscopy and tracheal intubation [20]. This
might prevent complications arising from a hypertensive emergency.
Neither the use of propofol in general nor a
thiopental dose exceeding 250 mg are licenced for
the use in pregnancy. Hence, their use is off-label
[16].
Despite no proven clinical superiority of propofol in obstetric anaesthesia, thiopental is increasingly replaced by propofol, as thiopental is no
longer available on the American market and
becomes more difficult and expensive to obtain in
a lot of European countries. Moreover, the use of
thiopental has recently been suggested as a risk
factor for accidental awareness during general
anaesthesia. In this survey, thiopental was used in
3% of anaesthetic inductions, but implicated in 23%
of the awareness reports [11 ].
In conclusion, there is a reasonable body of evidence to support the use of propofol as a standard
induction agent for general anaesthesia in caesarean
section in healthy, noncompromised patients. In the
presence of haemodynamic instability, ketamine
(11.5 mg/kg), etomidate (0.3 mg/kg) and a reduced
dose of propofol in association with a low dose of
opioids or ketamine are appropriate alternatives.
&&

Muscle relaxants
Muscle relaxants are used to facilitate endotracheal
intubation and to provide optimal surgical conditions. Until recently, succinylcholine 1 mg/kg
was standardly used for RSI because of its rapid
onset. Succinylcholine is highly ionized and poorly
lipid soluble, and only small amounts undergo
trans-placental transfer. However, possibly lifethreatening and well known side-effects stimulated
the search for a muscle relaxant with a more benign
safety profile.
Rocuronium was introduced in 1994. Due to its
rapid onset in higher doses, it soon gained popularity
for the RSI in the obstetric patient. Abouleish et al.
[21] showed that rocuronium 0.6 mg/kg in combination with thiopental 6 mg/kg provided acceptable
intubating conditions in 90% of the obstetric
patients. Rocuronium did not adversely affect neonatal Apgar-scores, acidbase measurements, time to
sustained respiration or neurobehavioural scores
[21]. However, the onset time of rocuronium for
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good intubation conditions was still slower than that


of succinylcholine. Increasing the initial dose to
1 mg/kg not only accelerated the onset time of neuromuscular blockade but also significantly prolonged
its duration of action, frequently beyond the end of
surgery. In addition, the fear of the long duration of
action in case of a difficult airway initially withheld
most anaesthesiologists from using rocuronium in
the pregnant population. Hence, the optimal rocuronium dose has been controversial over the last years.
hringer et al. [22] reported seven RSI for caesarean
Pu
section using thiopental (6 mg kg 1) and rocuronium
0.6 mg/kg and found acceptable intubation conditions in most of the cases. Interestingly, the
ED95 in nonobstetric patients is higher, that is
hringer et al. [22] attributed their find0.9 mg/kg. Pu
ings to the higher sensitivity of the obstetric patient
to muscle relaxants and the higher cardiac output.
McGuigan et al. [23], in contrast, suggested a higher
dose of rocuronium of 1 mg/kg in order to achieve
faster and better intubating conditions, without the
need to increase the doses of the hypnotic agent and
consequently compromising cardiovascular stability.
The fear of the prolonged duration of action of
rocuronium lasted until the introduction of suggamadex, a selective relaxant-binding agent, which
has been developed to rapidly reverse rocuronium-induced neuromuscular block. The sugammadexrocuronium interaction reduces the amount of
free rocuronium in plasma and leads to a shift of
rocuronium into the plasma, dramatically reducing
the level of rocuronium at the neuromuscular
junction.
Nauheimer et al. [24] were the first to describe
the use of sugammadex to reverse rocuronium block
in caesarean section patients. Using 1.0 mg/kg of
rocuronium for induction, the recommended dose
of sugammadex to achieve a reversal of profound
neuromuscular block (4 mg/kg) or moderate block
(2 mg/kg) was given at end of surgery and provided a
rapid and sufficient reversal to a train-of-four ratio of
0.9 in all patients within 2 min. The speed of recovery was dose-dependent, and reversal was sustained
without any signs of recurarization [24].
Of note, the safety profile of sugammadex has
not been completely established in parturients yet,
and there are still concerns regarding hypersensitivity and allergic reactions [25,26].
In conclusion, we suggest the use of rocuronium
1.0 mg/kg for RSI, followed by the application of
24 mg/kg sugammadex if no train-of-four ratio of
0.9 is achieved at the end of surgery. In our experience, this combination allows rapid onset and reversal of neuromuscular blockade with excellent
intubation conditions and avoidance of serious
side-effects [23,24].
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General anesthesia for caesarean section Devroe et al.

Opioids
Historically, opioids were administered only after
umbilical cord clamping in an attempt to avoid
respiratory depression of the neonate. The other
major concern arising from the use of opioids is
maternal hypotension with a possible negative
effect on the utero-placental perfusion and the foetal well-being.
However, in the presence of preeclampsia [27],
maternal cardiac [28] or neurologic disease, a
judicious use of opioids can provide haemodynamic
stability during airway manipulation and surgery
and hence offers protection from complications
resulting from the abrupt increase in arterial pressure that is frequently observed during endotracheal
intubation [29]. Furthermore, omission of opioids is
a risk factor for intraoperative awareness [12].
Huang et al. [13] demonstrated that general
anaesthesia for caesarean section in women with
preeclampsia is associated with an increased risk of
stroke when compared with neuraxial anaesthesia.
They could not find an increased risk of stroke
associated with general anaesthesia in women without preeclampsia [13]. One possible mechanism
may be related to the neuroendocrine stress
response, resulting in elevated plasma concentrations of catecholamines in preeclamptic women
who received general anaesthesia in comparison
with those who received neuraxial anaesthesia. This
increase of maternal plasma catecholamines compromises not only the health of the mother but also
causes utero-placental vasoconstriction, adversely
affecting the foetus.
Due to its rapid onset and offset, the use remifentanil has gained increasing popularity for obstetric general anaesthesia in high-risk women. A recent
meta-analysis on the maternal and foetal effects of
remifentanil for general anaesthesia in parturients
undergoing caesarean section found that remifentanil attenuated the maternal circulatory response
to intubation and surgery [14]. Unfortunately, this
meta-analysis did not distinguish between preeclamptic and healthy patients. Less negative base
excess and higher pH in the remifentanil-group
suggested a beneficial neonatal effect. It was concluded that an adequately powered trial addressing
neonatal side-effects of remifentanil is warranted.
Remifentanil doses differed strongly among the
included studies and doseresponse effects should
be further defined in order to find the optimal dose
for both mother and infant [14]. Park et al. [29]
demonstrated that a single bolus of remifentanil
of 0.5 or 1 mg/kg for induction of anaesthesia in
severely preeclamptic patients attenuated maternal
heart rate and pressor responses, with only minimal
and transient neonatal respiratory depression. They

suggested a dose of 0.5 mg/kg, as 1 mg/kg induced


arterial hypotension in 15% of patients [29]. More
recently, Yoo et al. [30 ] determined the effective
dose (ED50/ED95) of remifentanil to prevent the
pressor response to intubation in patients with
severe preeclampsia. Intubation-induced increases
of heart rate and blood pressure were attenuated in a
dose-dependent manner by remifentanil, with the
ED50 and ED95 being 0.59 [95% confidence interval
(95% CI) 0.470.70] and 1.34 (1.042.19) mg/kg,
respectively. However, all doses of remifentanil were
associated with a transient respiratory depression of
the newborn, and higher doses were associated with
maternal hypotension (13%) [30 ].
On the basis of available literature, we strongly
advise the use of remifentanil in preeclamptic and
other high-risk patients for whom marked haemodynamic fluctuations are dangerous. It is however
mandatory to anticipate neonatal resuscitation
when remifentanil is used.
In healthy parturients, the routine use of remifentanil for the induction of anaesthesia is more
controversial. However, this can be supported, as
it may reduce the incidence of maternal awareness
and improve maternal haemodynamic stability. If
the mandatory managing of brief infant respiratory
depression cannot be guaranteed in the local situation, remifentanil in healthy parturients should be
avoided [31,32].
&

&

Cricoid pressure and intubation


Expert opinion on the efficacy of cricoid pressure is
controversial [33,34], especially as its correct application is much more difficult than expected. The
force with which cricoid pressure is exerted should
be 10 N before induction and augmented to 30 N
after loss of consciousness [34]. Cricoid pressure
executed by untrained healthcare providers can be
applied with too little pressure to the anterior larynx
resulting in unreliable protection against regurgitation, or with too much pressure resulting in
obstructed views for tracheal intubation or difficult
placement of a supraglottis device [35,36].
Misapplication is probably the major cause of
ineffectiveness and complications of cricoid pressure. Adequate training has improved the effectiveness of cricoid pressure [36], and a newly introduced
device showed some potential to improve the
accuracy and reproducibility of cricoid pressure
[37]. Recently, Zeidan et al. [38 ] provided videolaryngoscopic and mechanical evidence (by advancing anorogastric tube) that a cricoid force of 30 N is
effective for the occlusion of the oesophageal
entrance in anaesthetized and paralyzed adult
patients. Applying adequate cricoid pressure and

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Obstetric and gynecological anesthesia

releasing it in case of difficult intubation is a wise


and well tolerated approach [34].
Three studies reported the well tolerated and
successful use of different types of laryngeal mask
airways (LMAs) (standard [39], LMAProseal [40],
LMASupreme [6]) in nearly 5000 patients as a routine
airway device for elective caesarean section under
general anaesthesia. These observations should be
interpreted cautiously and cannot be extrapolated
to emergency situations because above-mentioned
studies exclusively included slim, fasted and nonobese parturients for elective caesarean section. In
our practice, patients undergoing caesarean section
under general anaesthesia are seldom fasted, slim or
not in labour [41].
Gold standard for airway management in obstetric patients should remain cricoid pressure and
tracheal intubation. However, the insertion of an
LMA is a valuable alternative in case of a difficult
intubation or when maternal risks are associated
with tracheal intubation (e.g. in hypertensive emergencies or in patients with severe cardiopathies)
[41].

MAINTENANCE OF ANAESTHESIA
Notwithstanding limited evidence, sevoflurane has
become the maintenance agent of choice in general
anaesthesia for caesarean section. In the survey by
Murdoch et al. [16], sevoflurane was used in 52%,
followed by isoflurane (45%) and desflurane (1.6%).
Only 0.3% of the anaesthesiologists used propofol
for the maintenance of anaesthesia during caesarean
section.
Concentrations of volatile anaesthetics higher
than 1 minimum alveolar concentration (MAC)
should be avoided throughout the entire anaesthesia for caesarean section: before the delivery of the
baby because of the transplacental drug transfer and
consequent foetal depression; and after the delivery
of the baby due to the dose-dependent myometrialrelaxing properties of volatile anaesthetics [42].
Although anaesthetic requirements for volatile
anaesthetics are diminished by 2540% during pregnancy, maintenance of general anaesthesia for caesarean section with low concentrations of volatile
anaesthetics places parturients at an increased risk of
intraoperative awareness [11 ]. Nowadays, bispectral
index (BIS) monitoring is commonly used to monitor
depth of anaesthesia, whereas the isolated forearm
technique (IFT) is still the scientific gold standard for
detecting wakefulness during anaesthesia with neuromuscular blockade. After administration of thiopental 45 mg/kg and succinylcholine 12 mg/kg,
Zand et al. [43 ] found 41, 46 and 23% of the
parturients still obeying verbal commands at
&&

&

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laryngoscopy, intubation and skin incision. This


IFT responsiveness could not be predicted by the
BIS-monitoring. Only very low BIS values (<30) were
associated with the absence of responses to verbal
commands, suggesting that BIS monitoring is unreliable to detect IFT responsiveness during caesarean
section. However, the significance of these findings
remains controversial. Of note, no patient had evidence of explicit recall of intraoperative events. More
studies are required to determine long-term consequences of IFT responsiveness and to compare
IFT responsiveness using different anaesthetic techniques [44].
In our practice, the majority of parturients
appreciate if they are preoperatively informed that
the goal for general anaesthesia in caesarean section
is to provide well tolerated anaesthesia for both
mother and child and that the safety of the child
is achieved/maximized at the possible expense of an
increased risk of maternal awareness.
Because of the increased risk of postpartum
haemorrhage and uterine atony in case of caesarean
section, prophylactic uterotonic agents are incorporated in the routine anaesthetic management. A
recent meta-analysis advised a slow 0.31 IU-bolus
of oxytocin for elective caesarean section and a slow
3 IU-bolus of oxytocin for caesarean section in the
labouring parturient, followed by a 4-h infusion of
510 IU/h in both settings [45]. If uterine atony
occurs despite preventive measurements, Butwick
et al. [46 ] found an increased risk of haemorrhage-related morbidity if the caesarean section
was performed under general anaesthesia. This
effect was attributed to uterine relaxation caused
by volatile anaesthetics. Unfortunately, this study
did not mention specific drugs, doses or concentrations used during the procedures.
Maintenance with propofol can be safely used in
obstetric anaesthesia and could be an interesting
alternative to reduce the incidence of uterine atony
or when uterine atony is present [47]. However,
propofol also crosses the placenta with subsequent
dose-dependent foetal depression and was overrepresented in the audit on preoperative awareness
[11 ,42].
&

&&

CONCLUSION
RSI with cricoid pressure and endotracheal intubation remains the gold standard for all labouring
women undergoing emergency caesarean section
and for the majority of women having elective caesarean section under general anaesthesia. Because of
the limited availability of thiopental and the noninferiority of propofol, the latter becomes increasingly popular for induction. The combination of
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General anesthesia for caesarean section Devroe et al.

rocuronium and sugammadex combines rapid onset


and rapid reversal of neuromuscular blockade with a
greater safety profile than succinylcholine and very
comfortable intubation conditions. Although maintenance with propofol seems to be beneficial with
respect to the avoidance of uterine atony, sevoflurane
is still widely considered the maintenance agent of
choice in general anaesthesia for caesarean section.
Addition of opioids can attenuate the cardiovascular response to intubation in the preeclamptic
patient. The LMA is invaluable in obstetric anaesthesia as a rescue airway device or in selected cases in
which maternal comorbidity necessitates meticulous haemodynamic stability. Risks and benefits of
each technique must be evaluated in each individual case.
Acknowledgements
None.
Financial support and sponsorship
This work was only supported by the Department of
Anaesthesiology, University Hospitals Leuven, Belgium.
Conflicts of interest
There are no conflicts of interest.

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Volume 28  Number 3  June 2015

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.

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