BJA Advance Access published September 24, 2009

British Journal of Anaesthesia Page 1 of 6

doi:10.1093/bja/aep265

Magnesium sulphate has beneficial effects as an adjuvant during

general anaesthesia for Caesarean section
D. H. Lee* and I. C. Kwon

Department of Anaesthesiology and Pain Medicine, College of Medicine, Yeungnam University,

317-1 Daemyung Dong, Namgu, Daegu 705-717, Republic of Korea
*Corresponding author. E-mail: dhlee415@ynu.ac.kr
Background. The use of low concentrations of volatile anaesthetics with avoidance of opioids
may induce intraoperative awareness and adverse haemodynamic responses during Caesarean
section. Magnesium is well known to reduce anaesthetic requirements and to block noxious
stimuli. We investigated whether i.v. magnesium sulphate modulates anaesthetic depth and
analgesic efficacy during Caesarean section.
Methods. Seventy-two patients undergoing Caesarean section were randomly assigned to
receive i.v. saline (control group) or magnesium sulphate 30 mg kg21 bolusþ10 mg kg21 h21
continuous infusion (Mg 30 group) or 45 mg kg21 bolusþ15 mg kg21 h21 continuous infusion
(Mg 45 group) after induction. Bispectral index (BIS) value, mean arterial pressure (MAP), and
midazolam, fentanyl, and atracurium consumptions were recorded.
Results. BIS values [mean (SD)] at 7.5 and 10 min after surgery and before delivery in the
control [64 (9), 66 (8), 67 (8), P,0.001] and the Mg 30 groups [62 (8), P,0.01; 64 (7), 63 (9),
P,0.001] were higher than in the Mg 45 group [56 (8), 55 (8), 55 (7)]. MAP was greater in the
control group (P,0.05) than in the Mg 30 and Mg 45 groups during the pre-delivery period.
The magnesium groups required less midazolam (P,0.05), fentanyl (Mg 30, P,0.05; Mg 45,
P,0.01), and atracurium (P,0.001) vs the control group.
Conclusions. Preoperative i.v. magnesium sulphate attenuated BIS and arterial pressure
increases during the pre-delivery period. Magnesium sulphate can be recommended as an adju-
vant during general anaesthesia for Caesarean section to avoid perioperative awareness and
pressor response resulting from inadequate anaesthesia, analgesia, or both.
Br J Anaesth 2009
Keywords: anaesthesia, depth; anaesthesia, obstetric; monitoring, bispectral index;
pharmacology, magnesium sulphate
Accepted for publication: August 24, 2009

Low concentrations of volatile anaesthetic agents and the
avoidance of opioids until delivery have traditionally been
used for Caesarean section, because of concerns regarding
uterine atony and neonatal respiratory depression. As a
result, pregnant women undergoing general anaesthesia for
Caesarean section have a higher incidence of intraopera-
tive awareness than general surgical patients, especially
during the period before neonatal delivery.1 2 A previous
study demonstrated that the use of sevoflurane 1% in N2O
50% without analgesics failed to maintain bispectral index
(BIS) levels consistent with unconsciousness during
Caesarean section.3 Furthermore, adverse haemodynamic
stress responses such as severe increases in arterial
pressure due to inadequate anaesthesia, analgesia, or both
during the pre-delivery period can be a risk factor in
obstetric patients with pre-existing essential hypertension,
ischaemic cardiac disease, or increased intracranial or
intraocular pressure.
Magnesium sulphate has been widely used as a tocolytic
agent and an anticonvulsant for the treatment of preterm
labour and pre-eclampsia, respectively. On the other hand,
perioperative magnesium sulphate has been reported to
reduce anaesthetic requirements4 – 7 and to shorten anaes-
thetic induction by propofol.4 6 7 Moreover, in these
studies, the time required to reach a BIS value of 60 was
significantly less for magnesium-treated patients than

# The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
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 Lee and Kwon
untreated controls.4 6 7 In addition, magnesium has also
been reported to have antinociceptive effects in animal8
and human9 models of pain, and to reduce intraoperative
analgesic consumption.4 6 9 10
We therefore hypothesized that the anaesthetic and
analgesic potency of magnesium sulphate might be ben-
eficial in terms of attenuation of BIS increase and main-
taining stable haemodynamics via blockade of painful
stimuli before neonatal delivery. To our knowledge, no
other study has been conducted on the role of magnesium
sulphate as an anaesthetic adjuvant during Caesarean
section. In this study, we investigated the ability of mag-
nesium sulphate to modulate anaesthetic depth and analge-
sic efficacy in patients undergoing general anaesthesia for
Caesarean section.
Methods
After obtaining institutional review board approval and
informed consent, 75 ASA physical status _ subjects under-
going elective Caesarean section under general anaesthesia
were enrolled in this study. The indications for Caesarean
section were breech presentation, cephalopelvic dispropor-
tion, or previous Caesarean delivery. Patients with the fol-
lowing conditions were excluded from the study:
hypermagnesaemia, a known hypersensitivity to mag-
nesium sulphate, any degree of heart block, hypertension,
diabetes mellitus, cardiovascular, or kidney disease, labour
pain requiring analgesics, preterm, multiple gestation, pre-
operative fetal distress, or any other medical complication.
The subjects were randomly divided into one of the three
groups by using a computer-generated random number
table: the Mg 30 group (n¼25) received magnesium sul-
phate 10% (30 mg kg21) as an i.v. bolus and 10 mg kg21
h21 by a continuous infusion, the Mg 45 group (n¼25)
received magnesium sulphate 10% (45 mg kg21) as a bolus
and 15 mg kg21 h21 by a continuous infusion, and the
control group (n¼25) received a similar volume of saline
as bolus and continuous infusion. Each study drug was pre-
pared by the anaesthesiologist responsible for subject
grouping.
Before the induction of anaesthesia, standard monitoring
devices (Multi Channel Anaesthesia Monitor S/5TM ;
Datex-Ohmeda, Beaverton, OR, USA) were applied. A BIS
A-2000 monitorw (Aspect Medical Systems, Newton, MA,
USA) was used to continuously measure and display BIS
values. Muscle relaxation was monitored using a neuromus-
cular monitor (TOF-Watchw, Organon, Dublin, Ireland)
with two electrodes attached on the ulnar side of the wrist.
After obtaining baseline values for BIS and haemo-
dynamic variables, anaesthetic induction was performed
using thiopental sodium 4 mg kg21, followed by the bolus
study drug given over 15 – 20 s, and then succinylcholine
1 – 1.5 mg kg21, followed by the study drug given by con-
tinuous infusion by an attending anaesthesiologist who
Page 2 of 6
was blinded to the grouping and study drug. Cricoid
pressure was applied and the trachea was intubated 90 s
after administration of the succinylcholine. Atracurium
0.25 mg kg21 was administered for further muscle
relaxation.
Anaesthesia was maintained with 1.0% end-tidal sevo-
flurane and 1:1 O2/N2O at 3 litre min21. Ventilation of the
lungs was adjusted to maintain an end-tidal carbon dioxide
of 4.4 – 4.7 kPa. BIS values were recorded at 2.5 min inter-
vals from induction of anaesthesia to delivery. Mean arter-
ial pressure (MAP) and heart rates were measured before
the induction of anaesthesia; just after intubation; at 5 and
10 min after surgery; and before delivery. After delivery,
midazolam or fentanyl was administered, as required, to
achieve adequate sedation or analgesia to the end of
surgery. The target BIS range was 40– 60. If BIS values
exceeded 60 for more than 10 s, midazolam 0.05 mg kg21
was administered. Inadequate analgesia was defined as a
condition during which MAP or heart rate increased by
20% vs baseline and required fentanyl 1.0 mg kg21 for
management. Train-of-four (TOF) supramaximal neuro-
muscular stimulation (2 Hz, 50 mA) was measured at 5 min
intervals to the end of surgery and at 1 min intervals there-
after. Atracurium (0.1 mg kg21) was injected when a TOF
count exceeded two until 10 min before the end of surgery.
The total amounts of midazolam, fentanyl, and atracurium
administered after delivery were recorded, and divided by
subject’s body weight and surgery time (results are pre-
sented in mg kg21 h21). Times from induction to skin
incision, times from uterine incision to delivery, times from
induction to delivery, neonatal Apgar scores, and estimated
blood losses were also recorded.
Sevoflurane and N2O administration were immediately
discontinued after skin closure, and subjects were then ven-
tilated with O2 100% at 5 litre min21. Subjects were
allowed to recover spontaneously until the return of
T1¼25% or .2 responses on neuromuscular monitoring.
Then glycopyrrolate and pyridostigmine were administered
i.v. to reverse muscle relaxation. Tracheal tubes were
removed when BIS reached 80 and TOF ratio (T4/T1) was
.0.7. Times required to return to a T1 of 25%, to respond
to verbal commands (spontaneous eye opening), and to tra-
cheal extubation were recorded. All data were recorded by
an anaesthesiologist unaware of the study protocol and study
drugs used. Subjects were interviewed regarding intraopera-
tive recall on discharge from the postoperative care unit.
The primary outcome variable of the study was differ-
ence in the BIS value. On the basis of our pilot study, a
prior power analysis indicated that a minimum of 21 sub-
jects per group would be sufficient to detect a 10% differ-
ence in BIS values among the groups after the
administration of magnesium sulphate, with a study power
of 80% (b¼0.20) and a sensitivity of 95% (a¼0.05).
Intra-group differences were analysed by two-way
repeated-measures analysis of variance (ANOVA) with
Tukey’s post hoc test. Inter-group differences were
 Magnesium sulphate during Caesarean section

Table 1 Characteristics of patients. Values were expressed as mean (range or SD) or median (range)

Control group (n524) Mg 30 group (n523) Mg 45 group (n525)

Age (yr) 33.4 (26– 35) 36.4 (25 –38) 34.4 (26 –37)
Height (cm) 158.3 (4.3) 157.2 (5.9) 159.3 (5.7)
Weight (kg) 67.7 (8.6) 68.7 (10.6) 69.7 (7.4)
Induction to skin incision time (min) 3.2 (1.0) 3.1 (0.9) 3.4 (1.1)
Uterine incision to delivery time (min) 1.5 (0.5) 1.4 (0.6) 1.6 (0.4)
Induction to delivery time (min) 10.5 (1.4) 11.5 (2.4) 11.2 (2.4)
Apgar score at 1 min 9 (7– 9) 9 (8– 9) 9 (7 –9)
Apgar score at 5 min 9 (8– 10) 9 (8– 10) 9 (8 –10)
Estimated blood loss (ml) 401.3 (89.1) 397.3 (105.1) 384.7 (98.1)
Operating time (min) 65.2 (9.7) 64.4 (11.7) 67.3 (10.5)
Anaesthesia time (min) 81.3 (11.5) 79.3 (10.5) 80.3 (9.8)

Table 2 BIS values from induction of anaesthesia to delivery. Values were values [control group, 53 (9); Mg 30 group, 54 (9)], BIS
expressed as mean (SD). *P,0.05, †P,0.001 when compared with
pre-magnesium sulphate and ‡P,0.01, §P,0.001 when compared with the
values were significantly elevated at 5, 7.5, and 10 min
Mg 45 group after surgery, and pre-delivery in the control [61 (9), 64 (9),
66 (8), 67 (8), P,0.001] and Mg 30 groups [59 (7),
Control group Mg 30 group Mg 45 group
(n524) (n523) (n525) P,0.05; 62 (8), 64 (7), 63 (9), P,0.001]. However, BIS
values were unchanged during the pre-delivery period
Pre-induction 97 (9) 97 (8) 98 (8) in the Mg 45 group vs before magnesium sulphate adminis-
Pre-magnesium sulphate 53 (9) 54 (9) 54 (8)
2.5 min after surgery 56 (8) 55 (10) 56 (10)
tration [54 (8)].
5 min after surgery 61 (9)† 59 (7)* 58 (10) MAP and heart rates before induction were similar in
7.5 min after surgery 64 (9)†,§ 62 (8)†,‡ 56 (8) the three groups (Table 3). However, MAP was signifi-
10 min after surgery 66 (8)†,§ 64 (7)†,§ 55 (8)
Pre-delivery of neonate 67 (8)†,§ 63 (9)†,§ 55 (7)
cantly higher in the control group than in the Mg 30 and
Mg 45 groups post-intubation [112 (15) vs 101 (12),
P,0.05; 112 (15) vs 95 (11) mm Hg, P,0.001], at 5 min
[104 (9) vs 89 (7), P,0.001; 104 (9) vs 85 (10) mm Hg,
compared using one-way ANOVA with Scheffe’s post hoc P,0.001] and at 10 min [102 (7) vs 87 (9), P,0.01; 102
test among the groups. P-values of ,0.05 were considered (7) vs 84 (11) mm Hg, P,0.001] after surgery, and pre-
significant. Statistical analysis was performed using delivery [96 (6) vs 85 (9), P,0.05; 96 (6) vs 83 (11) mm
SPSSw 17.0 software (SPSS Inc., Chicago, IL, USA). Data Hg, P,0.01]. When compared with pre-induction values,
are expressed as mean (range or SD) or median (range). MAP was higher post-intubation, at 5 and 10 min after
surgery, and pre-delivery in the control group (P,0.001),
but was only higher post-intubation in the Mg 30
(P,0.001) and Mg 45 (P,0.01) groups. No significant
Results difference was observed between MAP values in the
Seventy-two subjects completed the study. Three subjects magnesium-treated groups, and heart rates were similar for
were excluded from the analysis because the pre-delivery all groups.
period was ,10 min (one in the Mg 30 group) or because Midazolam, fentanyl, and atracurium consumptions are
of technical problems with the neuromuscular monitor presented in Table 4. Midazolam consumption was signifi-
(one in the control group and one in the Mg 30 group). cantly lower in the Mg 30 [75.9 (19.7) mg kg21 h21,
There were no differences in patient characteristic data P,0.05] and Mg 45 groups [67.5 (18.3) mg kg21 h21,
and maternal and neonatal outcome variables among the P,0.05] than in the control group [103.7 (23.1) mg kg21 h21].
study groups (Table 1). No neonate required resuscitation Significantly lower doses of fentanyl were required by the
in all three study groups. Mg 30 [0.4 (0.3) mg kg21 h21, P,0.05] and Mg 45
BIS changes from induction of anaesthesia to delivery groups [0.2 (0.2) mg kg21 h21, P,0.01] than by the
are shown in Table 2. BIS values during the pre-induction control group [1.1 (0.4) mg kg21 h21], and atracurium
period were similar in all three study groups. BIS values doses were significantly lower in the Mg 30 [220.3 (67.8)
remained at ,60 in all subjects until 2.5 min after the mg kg21 h21, P,0.001] and Mg 45 groups [183.7 (78.1)
initiation of surgery. However, BIS values at 7.5 and 10 mg kg21 h21, P,0.001] than in the control group [340.7
min after surgery, and pre-delivery in the control [64 (9), (81.7) mg kg21 h21]. No difference was observed between
66 (8), 67 (8), P,0.001] and Mg 30 groups [62 (8), drug consumptions in the Mg 30 and Mg 45 groups.
P,0.01; 64 (7), 63 (9), P,0.001] were significantly higher Maternal recovery times were not significantly different
than in the Mg 45 group [56 (8), 55 (8), 55 (7)]. When among the groups (Table 5), and no patient experienced
compared with pre-magnesium sulphate administration intraoperative recall.

Page 3 of 6
 Lee and Kwon

Table 3 MAP and heart rates from induction of anaesthesia to delivery. Values were expressed as mean (SD). *P,0.05, †P,0.01, ‡P,0.001 when compared
with pre-induction and §P,0.05, kP,0.01, }P,0.001 when compared with the control group. No significant differences were found between heart rates in the
three groups. MAP, mean arterial pressure; HR, heart rate

Pre-induction Post-intubation 5 min after surgery 10 min after surgery Pre-delivery of neonate

MAP (mm Hg)

Control group 86 (5) 112 (15)‡ 104 (9)‡ 102 (7)‡ 96 (6)‡
Mg 30 group 88 (4) 101 (12)‡,§ 89 (7)} 87 (9)k 85 (9)§
Mg 45 group 87 (6) 95 (11)†,} 85 (10)} 84 (11)} 83 (11)k
HR (beats min21)
Control group 77 (7) 101 (15)‡ 94 (11)‡ 91 (10)‡ 88 (10)‡
Mg 30 group 79 (8) 102 (16)‡ 94 (10)‡ 89 (11)† 87 (7)†
Mg 45 group 82 (6) 103 (17)‡ 92 (11)* 89 (13) 85 (11)

Table 4 Midazolam, fentanyl, and atracurium consumption after delivery of Table 5 Maternal recovery time (min). No significant differences were found
neonate. Values were expressed as mean (SD). *P,0.05, †P,0.01, ‡P,0.001 between recovery times in the three groups. Values were expressed as mean
when compared with the control group. No significant differences were found (SD)
between drug consumptions in the Mg 30 and Mg 45 groups
Control group Mg 30 group Mg 45 group
Control group Mg 30 group Mg 45 group (n524) (n523) (n525)
(n524) (n523) (n525)
Time to T1¼25% 6.3 (3.1) 6.4 (2.8) 7.0 (3.4)
Midazolam (mg kg21 h21) 103.7 (23.1) 75.9 (19.7)* 67.5 (18.3)* Time to eye opening 9.9 (3.5) 10.1 (2.9) 10.5 (2.6)
Fentanyl (mg kg21 h21) 1.1 (0.4) 0.4 (0.3)* 0.2 (0.2)† Extubation time 10.2 (3.3) 10.5 (3.6) 10.9 (2.9)
Atracurium (mg kg21 h21) 340.7 (81.7) 220.3 (67.8)‡ 183.7 (78.1)‡

infusion reduced sufentanil consumption but did not sig-

Discussion
This is the first randomized, double-blind, placebo-
controlled study to investigate the effects of magnesium
during Caesarean section. Our results show that the pre-
operative administration of magnesium sulphate not only
attenuates increases in arterial pressure resulting from
noxious stimuli, but that 45 mg kg21 of magnesium sulphate
as a bolus and 15 mg kg21 h21 by a continuous infusion
effectively prevents awareness, as indicated by attenuated
BIS increases during the pre-delivery period in patients
under general anaesthesia for Caesarean section. The study
also demonstrates that after neonatal delivery, midazolam,
fentanyl, and atracurium consumptions were significantly
lower in the magnesium groups than in the control group.
In the present study, we used BIS monitoring and chose
a BIS target range of 40 – 60. Because BIS levels correlate
well with depth of sedation,11 12 and are increased by not
only awareness13 but also sympathetic activation,14 BIS
monitoring can be a useful means of detecting inadequate
sedation, analgesia, or both during general anaesthesia for
Caesarean section. BIS values below 60 indicated a low
probability of recall and intraoperative awareness in the
majority of studies.12 15 16 We observed that the induction
of anaesthesia with thiopental and maintenance with 1.0%
end-tidal sevoflurane in N2O 50% in the control group did
not reliably produce BIS values below 60 during the
period between 5 min after surgery and delivery, which
concurs with the result of previous study.3
The role of magnesium sulphate on BIS response is deba-
table in a few studies. In one previous study, when patients
received either sufentanil infusion or sufentanil plus
magnesium sulphate (2 g h21 infusion), the magnesium
nificantly change BIS values.17 However, in this study,
average BIS values were kept in the range 61– 88 by
decreasing or increasing sufentanil infusion in both
groups, and immediate BIS values after the administration
of magnesium sulphate were not presented. In another
study, the authors suggested that one of the reasons for the
BIS increase observed in their study was a reduced propo-
fol requirement resulting from the anaesthetic effect of
magnesium sulphate.5 On the other hand, in another study,
i.v. magnesium sulphate (30 mg kg21 as a bolus dose fol-
lowed by a continuous infusion of 10 mg kg21 h21) not
only significantly reduced total midazolam consumption,
but also decreased BIS values over 10 min after adminis-
tration in patients under monitored anaesthesia care for
shockwave lithotripsy.18 In the present study, although BIS
values increased above 60 from 7.5 min after surgery in
the Mg 30 group, the time required to reach a BIS value
of above 60 was substantially later in the Mg 30 group
compared with the control group. Moreover, in the Mg 45
group, mean BIS values remained in the target range
during the entire pre-delivery period.
Recent studies have demonstrated that magnesium
administration significantly reduces anaesthetic drug
requirements.4 – 7 18 19 Similar to other studies,18 20 we also
observed a significant reduction in midazolam consump-
tion during the operation period in magnesium-treated sub-
jects. This finding, in addition to the observed attenuations
of BIS increases, suggests that magnesium sulphate may
have a sedative effect and, thus, might be beneficial in
patients undergoing general anaesthesia for Caesarean
section who have a high risk of awareness, especially
during the pre-delivery period.

Page 4 of 6
 Magnesium sulphate during Caesarean section
Noxious stimuli, such as laryngoscopy, orotracheal intu-
bation, and skin and uterine incisions, are frequent during
the period before neonatal delivery, but despite the need
for adequate analgesia during this period, opioids are
usually avoided because of the risk of neonatal respiratory
depression. However, no side-effect-free agent that specifi-
cally inhibits nociception during Caesarean section has yet
been identified. In the present study, haemodynamic
responses to noxious stimuli during the pre-delivery period
were effectively blunted in the magnesium-treated groups,
with no significant inter-group differences. From post-
intubation to pre-delivery, MAP remained at a significantly
lower level in magnesium sulphate-treated subjects than in
controls; this probably indicates that the analgesic proper-
ties of magnesium sulphate reduce sympathetic stimu-
lation. Furthermore, mean intraoperative fentanyl
consumptions in the Mg 30 and Mg 45 groups were sig-
nificantly less than in the control group. This finding is in
accord with previous studies, which found that the use of
magnesium sulphate as an adjuvant reduces analgesic
requirements during the perioperative period under general
anaesthesia.6 9 10
Magnesium is a physiologic calcium channel blocker21
and a non-competitive N-methyl-D-aspartate (NMDA)
receptor antagonist,22 and these properties appear to play
an important role in the prevention and treatment of peri-
operative pain.23 24 Furthermore, the potency of volatile
anaesthetics can be increased by non-competitive NMDA
antagonist, and the analgesic effects of magnesium are
probably enhanced by volatile anaesthetics.25 Taken
together, we suggest that antagonism of NMDA receptor
and blockade of calcium channel by magnesium could be
responsible for the modification of perioperative sedation
and analgesia observed in the present study. On the other
hand, magnesium blocks the release of catecholamines26 27
and produces vasodilatation by acting directly on blood
vessels,28 and thus, we cannot exclude the possibility that
those effects could have partly contributed to the improved
arterial pressure control observed in the Mg 30 and Mg 45
groups. However, obviously further studies are needed to
identify the precise mechanism.
It is well known that magnesium sulphate prolongs and
potentiates neuromuscular block by non-depolarizing neu-
romuscular blocking agents,29 and our results support pre-
vious clinical studies4 10 by demonstrating that magnesium
lowers neuromuscular blocker requirements. In a previous
study, magnesium sulphate was found to delay postopera-
tive recovery.7 However, in the present study, maternal
emergence and recovery were virtually identical in the
three groups, probably because neuromuscular trans-
mission was monitored throughout the operation,
additional doses of atracurium were administered accord-
ing to the TOF count .2 criterion, atracurium injections
were discontinued from 10 min before the end of surgery,
and atracurium consumptions were lower in the
magnesium-treated groups than in the control group.
Page 5 of 6
One limitation is that serum magnesium concentrations
were not measured in our study. However, the doses of
magnesium sulphate used in the present study were lower
than those used to treat pre-eclampsia, which requires a
loading dose of magnesium sulphate 4 g, followed by 1 –2
g h21 as a maintenance dose,30 and were within the ranges
used in previous investigations.4 6 19 31 In addition, pre-
vious studies, in which similar magnesium regimen was
used, had noted almost 1.4– 1.8 times increase in serum
magnesium concentrations.5 9 32 No increase in blood loss
or uterine atony occurred, and no adverse neonatal effects
were observed at the dosages used in the present study.
In conclusion, our results show that the preoperative
administration of magnesium sulphate reduced intraopera-
tive requirements for midazolam, fentanyl, and atracurium.
Furthermore, magnesium sulphate effectively attenuated
BIS and arterial pressure increases during the period
before neonatal delivery. Our findings indicate that mag-
nesium sulphate can be recommended as an adjuvant
during general anaesthesia for Caesarean section, to avoid
perioperative awareness and pressor response resulting
from inadequate anaesthesia, analgesia, or both.
Funding
This research was supported by the Yeungnam University
Research Grants in 2007.
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