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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


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

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

Table 1
Demographic data.

Parameters Magnesium Control p value

Age (years) (mean SD) 35.28 9.77 37.35 13.09 0.353


Weight (kg) (mean SD) 55.80 6.88 58.17 8.21 0.107
Height (cm) (mean SD) 164 6.17 163.33 5.94 0.569
Gender Males, n (%) 36 (66.7) 31 (57.4) 0.321
Females, n (%) 18 (33.3) 23 (42.6)
ASA I, n (%) 51 (94.4) 46 (85.2) 0.112
II, n (%) 3 (5.6) 8 (14.8)

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
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