Acta Anaesthesiologica Taiwanica xxx (2016) 1e3

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Research Paper

Magnesium sulfate for postoperative analgesia after surgery under

spinal anesthesia
Prerana N. Shah*, Yamini Dhengle
Department of Anaesthesiology, Seth GSMC & KEM Hospital, Maharashtra, India

a r t i c l e i n f o a b s t r a c t

Article history: Background: Magnesium has been proven to have antinociceptive effects in animal and human models of
Received 16 September 2015 pain. Its effect is primarily based on the regulation of calcium inux into the cell, which is natural
Received in revised form physiological calcium antagonism and N-methyl-D-aspartate (NMDA) receptor antagonism.
10 May 2016
Methods: One hundred and eight patients undergoing surgery with spinal anesthesia received either
Accepted 16 June 2016
250 mg of intravenous magnesium sulfate followed by an infusion of 500 mg magnesium sulfate (25 mg/
mL) at the rate of 20 mL/hour; or the same volume of normal saline (control group) as bolus and infusion.
Keywords:
The primary end-points in the study were to evaluate the analgesic effect and duration of sensory and
anesthesia;
analgesia;
motor blockade. The secondary end-points included assessment of hemodynamic effects of intravenous
bupivacaine; magnesium sulfate and rescue analgesia requirement.
magnesium sulfate; Results: Sensory and motor blockade, respectively, were 25 minutes and 34 minutes shorter in the
postoperative; control group. Less patients in the magnesium group (33% vs. 53.7%) than in control group required
spinal rescue analgesia in the postoperative period. The control group required rescue analgesia nearly 3 hours
earlier than the magnesium group. Only one patient in the control group experienced bradycardia. There
was no event of intraoperative hypotension in either of the groups.
Conclusion: Intravenous magnesium sulfate when given as a bolus, followed by an infusion, delayed and
decreased the need of rescue analgesics after spinal anesthesia.
Copyright 2016, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction Studies related to magnesium sulfate administration reveal that

Postoperative pain should be effectively treated because it
represents an important component of postoperative recovery.
Effective treatment serves to blunt autonomic, somatic and endo-
crine reexes with a resultant potential decrease in perioperative
morbidity. The most common treatment practice is a poly-
pharmacological approach.1 Noxious stimulation leads to the
release of glutamate and aspartate neurotransmitters, which bind
to various subclasses of excitatory amino acid receptors, including
the N-methyl D-aspartate (NMDA) receptor. Activation of NMDA
receptors leads to calcium and sodium inux into the cell, with an
efux of potassium and initiation of central sensitization and wind-
up. Magnesium blocks NMDA channels in a voltage-dependent
way, and its addition produces a reduction of NMDA-induced
currents.2
Conicts of interest: The authors declare no conicts of interest relevant to this
article.
* Corresponding author. Department of Anaesthesiology, Seth GSMC & KEM
Hospital, Parel, Mumbai 400012, Maharashtra, India
E-mail: pps@kem.edu (P.N. Shah), yamini008@rediffmail.com (Y. Dhengle).
the anesthetic and analgesia quality may improve.3 The true site of
action of magnesium is probably at the spinal cord NMDA re-
ceptors. Hence, it has been used as an adjunct to analgesics and
anesthetic agents for intraoperative and postoperative analgesia.3
Several recent reports have described the efcacy of magnesium
infusions in moderate dosage both during surgery and in the
postoperative period for decreasing postoperative analgesic
requirements.3,4
2. Methods
The study was approved by the Ethics Committee for Research
on Human Subjects, Seth G.S. Medical College & KEM Hospital,
Parel, Mumbai 400012. Vide EC/219/2012 and Dr Kamal Hazari as
chairperson on 21 January, 2013.
After written informed consent, 108 patients, posted for lower
abdominal and lower limb surgeries under spinal anesthesia, were
studied in this prospective and randomized double-blinded study.
In accordance with a previous study carried out by Apan et al,5 the

http://dx.doi.org/10.1016/j.aat.2016.06.003
1875-4597/Copyright 2016, Taiwan Society of Anesthesiologists. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Shah PN, Dhengle Y, Magnesium sulfate for postoperative analgesia after surgery under spinal anesthesia, Acta
Anaesthesiologica Taiwanica (2016), http://dx.doi.org/10.1016/j.aat.2016.06.003
2 P.N. Shah, Y. Dhengle
visual analog scale (VAS) score was considered as the primary end-
point. Standard deviation was 24 in the control group and 16 in the
magnesium group. To nd a difference in both the groups regarding
VAS, with the power of the study at 80% and keeping alpha error at
5%, 54 patients were needed per group. The randomization was
computer based, and patients were either assigned to the magne-
sium group or the control group. The primary end-points in the
study were to evaluate the analgesic effect and duration of sensory
and motor blockade. The secondary end-points included assess-
ment of hemodynamic effects of intravenous magnesium sulfate
and rescue analgesia requirement.
American Society of Anesthesiologists physical status I and II
patients undergoing surgery under spinal blockade, within the age
group of 18e65 years and height within 150e180cm were included.
Patients with severe or controlled systemic diseases, neurological,
cardiovascular, respiratory disease, bleeding disorders, renal
dysfunction or congenital disorders; those receiving calcium
channel blockers or previous administration or allergy of magne-
sium sulfate were excluded. Pregnant females, lactating mothers
and patients allergic to bupivacaine were also excluded.
An injection of 15 mg (3 mL) of 0.5% hyperbaric bupivacaine was
given intrathecally in the L3eL4 space. The patient was made su-
pine, then 0.5 mL (250 mg) of magnesium sulfate was given
intravenously, followed by an infusion of 500 mg magnesium sul-
fate (25mg/mL) at the rate of 20 mL/hour in the magnesium group;
or the same volume of normal saline (control group) as bolus and
infusion was given. This was injected through another vascular
access used exclusively for this purpose. The anesthesiologist
evaluating the patient was not aware of which group the patient
was in.
Duration of sensory block was dened as the time between in-
jection of intrathecal bupivacaine and regression to L1 dermatome
level. Duration of motor block was dened as the time between
injection of intrathecal bupivacaine and recovery of knee exion
and ability to lift the knee at least 10 cm from bed surface. Heart
rate and mean blood pressure (MAP) was measured every 4 hours.
Bradycardia [heart rate < 55 beats per minute (bpm)] or hypoten-
sion (mean blood pressure < 70% of base line) were monitored and
appropriately managed.
Postoperatively, the VAS score (scale in millimeters on a 10-cm
line with numbers from 0 to 10; 0 no pain and 10 worst pain
imaginable) was used to assess analgesia every 4 hours for 24
hours. Rescue analgesia (intravenous tramadol 50 mg) was given
when VAS score exceeded 3. Sedation was evaluated according to a
four-point rating scale. 1, Patient fully awake; 2, patient somnolent
but responds to verbal commands; 3, patient somnolent but re-
sponds to tactile stimuli; 4, patient asleep but responds to pain.
Patients were monitored and appropriately treated for other side
effects such as a burning or heat sensation at the site of injection, or
pruritus.
Descriptive statistics was used for categorical data. Data was
analyzed using professional statistics package EpiInfo 7.0 (Centers
Table 1
Demographic data.
Parameters
Age (years) (mean SD)
Weight (kg) (mean SD)
Height (cm) (mean SD)
Gender Males, n (%)
Females, n (%)
ASA I, n (%)
II, n (%)
ASA American Society of Anesthesiologists.
Please cite this article in press as: Shah PN, Dhengle Y, Magnesium sulfate for postoperative analgesia after surgery under spinal anesthesia, Acta
Anaesthesiologica Taiwanica (2016), http://dx.doi.org/10.1016/j.aat.2016.06.003
for Disease Control and Prevention (CDC) in Atlanta, Georgia, USA)
version for windows. Descriptive data was represented as mean
standard deviation for numeric variables, and percentages and
proportions for categorical variables. Appropriate tests of signi-
cance like the independent t-test and Chi-square test were used
depending on the nature and distribution of variables. Values of
p < 0.05 were considered statistically signicant.
3. Results
Demographic data with respect to age, weight, height, gender,
and American Society of Anesthesiologists grade was comparable
and is depicted in Table 1.
The types of surgeries included lower limb orthopedic and
lower abdominal surgeries and were comparable in both groups
(Table 2). The duration of the surgery was about 71 minutes in both
groups.
The postoperative VAS score, as shown in Figure 1 and Table 3,
was analyzed by dividing the score into ranges of 0e3, 4e6 and
7e10. In the immediate postoperative period, no patient had a VAS
score more than 6. One patient in the magnesium group and seven
in the control group had a VAS score of 4e6, which was statistically
signicant (p 0.006). Whereas at the 4-hour interval, seven pa-
tients in the magnesium group and 17 patients in the control group,
had a VAS score of 4e6, which was also statistically signicant
(p 0.001).
The duration of sensory blockade in the magnesium group was
128.04 14.97 minutes and in the control group was 103.89 12.27
minutes; a difference of about 25 minutes was observed which was
statistically signicant (p 0.001). The duration of motor blockade
in the magnesium and control groups was 154.89 18.73 minutes
and 120.52 11.12 minutes, respectively, amounting to a difference
of about 34 minutes between the two groups; this difference was
also signicant statistically (p 0.001). A total of 18 patients in the
magnesium group required rescue analgesia, amounting to 33.3% of
the group. In the control group, 29 patients required rescue anal-
gesia, amounting to 53.7% of the group (Table 4). The lower number
of patients in the magnesium group requiring rescue analgesia was
also a statistically signicant difference (p 0.033). The control
group required rescue analgesia earlier than the magnesium group.
The magnesium group required rescue analgesia at 7.89 4.31
hours, whereas the control group required it earlier at 4.59 4.01
hours in the postoperative period (p 0.009).
There was no signicant difference in MAP found between the
magnesium group and the control group. Only one patient in the
control group experienced bradycardia, which was treated with
intravenous atropine 0.6 mg. None of the patients in the magne-
sium group experienced bradycardia. There was no event of intra-
operative hypotension in either of the groups.
There was no statistical difference in the sedation score in both
the magnesium and control groups. Three patients experienced
ushing in the magnesium group.
Magnesium Control p value
35.28 9.77 37.35 13.09 0.353
55.80 6.88 58.17 8.21 0.107
164 6.17 163.33 5.94 0.569
36 (66.7) 31 (57.4) 0.321
18 (33.3) 23 (42.6)
51 (94.4) 46 (85.2) 0.112
3 (5.6) 8 (14.8)
Magnesium sulfate for analgesia 3

Table 2 postoperative analgesics. The VAS scores in the immediate post-

Type of surgeries. operative period were signicantly less in the magnesium group.
Type of surgery (%) Magnesium Control The analgesic properties of magnesium are due to the NMDA
Lower limb implant xation 17 (31.4) 13 (24)
glutamate receptor blocking action, which hampers calcium entry
Lower limb debridement and wound wash 13 (24.07) 9 (16.66) into the cell and the initiation of central sensitization process. Two
Knee arthroscopy 2 (3.7) 3 (5.55) earlier clinical studies showed that VAS scores were signicantly
Stoma closure 1 (1.85) 3 (5.55) lower in patients receiving perioperative magnesium.7,8
Perianal surgery 3 (5.55) 6 (11.11)
In our study, the duration of sensory blockade as well as motor
Hernioplasty 2 (3.7) 5 (9.25)
Hydrocele repair 2 (3.7) 0 (0) blockade in the magnesium group was signicantly more than that
Open appendicectomy 14 (25.9) 13 (24) in the control group. However, studies carried out by Apan et al and
Lower limb split skin grafting 0 (0) 2 (3.7) Kumar et al did not show any signicant difference among the two
groups in this regard.5,8
We observed that magnesium decreased the requirement for
postoperative rescue analgesia as well as delaying its requirement.
The mean analgesic consumption or the total dose of analgesics
required in patients who received perioperative intravenous mag-
nesium infusion was lower compared to the control group in pre-
vious studies.5e7. A study which used patient controlled analgesia
showed that analgesia consumption and additional rescue anal-
gesia required were lower in the magnesium group.9 Ko et al10
included patients for abdominal hysterectomy under general
anesthesia with epidural, and patient controlled analgesia. They
found that the perioperative use of intravenous magnesium did not
have any effect on postoperative pain, attributing this nding to the
lack of increase in magnesium levels in cerebrospinal uid
following its intravenous administration. The limitations of our
study are that reduced pain scores and reduced requirements for
Figure 1. Postoperative VAS scores.
postoperative analgesia in the magnesium group could be a result
of the longer block, rather than a reduction in nociception. The
Table 3
study did not allow a separation of the longer spinal blockade
Postoperative VAS Score. versus the potential analgesic effect of magnesium.
Time interval Magnesium, n (%) Control, n (%) p value
(Fisher test) 5. Conclusion
VAS VAS VAS VAS
0e3 4e6 0e3 4e6

Immediate 53 (98.14) 1 (1.85) 47 (87.03) 7 (12.96) 0.03 The observations of this study suggest that intravenous mag-
postoperative nesium sulfate given as a bolus of 250 mg, followed by an infusion
period of 500 mg/hour improved postoperative analgesia by delaying as
4h 47 (87.03) 7 (12.96) 37 (68.51) 17 (31.48) 0.018 well as decreasing the need of postoperative analgesics. It also
8h 51 (94.44) 3 (5.55) 52 (96.29) 2 (3.70) 0.318
12 h 49 (90.7) 5 (9.25) 53 (98.14) 1 (1.85) 0.328
prolonged the duration of sensory and motor blockade of spinal
16 h 52 (96.29) 2 (3.7) 53 (98.14) 1 (1.85) 0.379 anesthesia. There was no signicant difference in hemodynamic
20 h 54 (100) 0 (0) 54 (100) 0 (0) > 0.99 variables and sedation in both groups.
24 h 54 (100) 0 (0) 54 (100) 0 (0) > 0.99

VAS visual analog scale.

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Please cite this article in press as: Shah PN, Dhengle Y, Magnesium sulfate for postoperative analgesia after surgery under spinal anesthesia, Acta
Anaesthesiologica Taiwanica (2016), http://dx.doi.org/10.1016/j.aat.2016.06.003