|Year : 2016 | Volume
| Issue : 3 | Page : 416-421
Magnesium sulfate at two different doses as an adjuvant to bupivacaine in infraumblical (below knee) orthopedic surgeries under spinal anesthesia
Sudarshan Kumar Chaudhary, Ravinder Kumar Verma, Shelly Rana MD, DNB , Jai Singh, Amruth Danesh
Department of Anaesthesia, DRPGMC, Kangra at Tanda, Himachal Pradesh, India
|Date of Submission||29-Aug-2015|
|Date of Acceptance||06-Apr-2016|
|Date of Web Publication||31-Aug-2016|
Department of Anaesthesia, DRPGMC, Kangra at Tanda, Himachal Pradesh
Source of Support: None, Conflict of Interest: None
The use of magnesium sulfate as an adjuvant in neuraxial block has gained popularity, with the aim of improving and enhancing the quality and duration of anesthesia, delaying the onset of postoperative pain, and thus reducing the demand for postoperative rescue analgesics. However, until today, there has been no consensus as regards the ideal dose of magnesium sulfate as an adjuvant in the subarachnoid block. The present study was designed to examine whether the addition of intrathecal magnesium sulfate (50 and 100 mg) would enhance the analgesic efficacy of intrathecal bupivacaine. We hypothesized that the additive effect of magnesium sulfate as an adjuvant to bupivacaine in subarachnoid block is dose dependent.
Materials and methods
This study was carried out on 90 American Society of Anesthesiology I and II patients of both sexes in the age group of 20–60 years scheduled for below knee surgeries under subarachnoid block. Group 1 (n = 30) patients received intrathecal 0.5% heavy bupivacaine (2.8 ml) +0.2 ml normal saline; group 2 (n = 30) received intrathecal 0.5% heavy bupivacaine (2.8 ml) +50 mg (0.1 ml) magnesium sulfate +0.1 ml normal saline; and group 3 (n = 30) received intrathecal 0.5% heavy bupivacaine (2.8 ml)+100 mg (0.2 ml) magnesium sulfate. The primary outcome measure was the duration of postoperative analgesia, and secondary outcomes included the number of supplemental analgesic requirements, block characteristics, and hemodynamic stability.
The onset of sensory and motor block was delayed in the magnesium group (100 mg>50 mg). There was a significant prolongation of postoperative analgesia in the magnesium group in a dose-dependent manner, and total dose of rescue analgesic requirement was found to be significantly delayed in the 100 mg group. Patients in all groups remained hemodynamically stable without any adverse effects.
Magnesium sulfate (100 mg) as an adjuvant to bupivacaine in subarachnoid block prolongs the duration of analgesia and decreases the demand for rescue analgesics compared with the control and the magnesium sulfate 50 mg group.
Keywords: adjuvants, analgesia, anesthesia, magnesium sulfate, pain, postoperative
|How to cite this article:|
Chaudhary SK, Verma RK, Rana S, Singh J, Danesh A. Magnesium sulfate at two different doses as an adjuvant to bupivacaine in infraumblical (below knee) orthopedic surgeries under spinal anesthesia. Ain-Shams J Anaesthesiol 2016;9:416-21
|How to cite this URL:|
Chaudhary SK, Verma RK, Rana S, Singh J, Danesh A. Magnesium sulfate at two different doses as an adjuvant to bupivacaine in infraumblical (below knee) orthopedic surgeries under spinal anesthesia. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2021 Apr 14];9:416-21. Available from: http://www.asja.eg.net/text.asp?2016/9/3/416/189571
The study was presented in CME Cum HP Chapter ISA at Shimla on 9th September 2014.
| Introduction|| |
Neuraxial blocks are currently most popular and accepted than ever since the late 19th century (1885) for lower limb surgeries. Subarachnoid block is preferred over epidural route, because of its rapid onset, good density block, lower failure rates, no catheter-related complications, and cost-effectiveness, but has the limitations of shorter duration of block and inability to extend the analgesia into the postoperative period .
In recent years, the use of intrathecal adjuvants has gained popularity, with the intention of reducing the dose of local anesthetics, maintaining hemodynamic stability, delaying the onset of pain during the postoperative period, and thus reducing the demand for postoperative rescue analgesics. Addition of adjuvants ensures faster recovery, enabling patients to return to their routine activity more quickly . Most commonly used adjuvant in central neuraxial blocks are opioids ; however, their adverse effects such as respiratory depression, nausea and vomiting, constipation, and pruritis have prompted further research to develop nonopioid adjuvants with less worrisome side effects .
Clonidine, ketamine, and neostigmine have been added to intrathecal local anesthesia in the presence and absence of opioids to prolong analgesia and reduce the side effects of intrathecal opioids ,,. In the last decade, major technological breakthroughs in the field of postoperative analgesia has occurred. With the discovery of the N-methyl-D-aspartate (NMDA) receptors and its links to nociceptive pain transmission and central sensitization, there has been interest in utilizing noncompetitive NMDA receptor antagonists, such as ketamine, magnesium sulfate, and dextromethorphan, as potential analgesic agents.
Recent studies ,, suggested that magnesium sulfate can play a beneficial role also in spinal anesthesia when administered through the intrathecal route. Keeping in mind the advantages and the revealed side effect profile of this drug, this study was conceived to evaluate and compare the efficacy of two doses of magnesium sulfate (50 and 100 mg) as an intrathecal adjuvant to bupivacaine.
| Materials and methods|| |
After approval by the Institutional Ethics Committee (CTRI/2015/07/005963), this study was carried out on 90 American Society of Anesthesiologist I/II patients of either sex in the age group of 20–60 years scheduled for below knee surgeries (fracture shaft tibia, fracture tibial condyle, and fracture ankle) under subarachnoid block over a period of 18 months from January 2013 to June 2014 in the Department of Anaesthesia.
Patient's refusal for block, having bleeding disorders, local infections at the site where needle for block is to be inserted, history of seizures, respiratory or cardiac diseases, patients on calcium channel blockers, and patients with basal metabolic index greater than 30 kg/m2 were excluded from the study.
Randomization was achieved using a computer-generated random number table. The random group assigned was enclosed in a sealed opaque envelope to ensure concealment of allocation sequence. After shifting the patient to the operation theater, the sealed envelope was opened by the anesthesiologist not involved in the study to prepare the drug solution according to randomization. The observer who collected the perioperative data and the patients were blinded to the drug solution administered. Three groups received the premixed coded solution as per randomization.
Group 1 (n = 30) patients received 2.8 ml of intrathecal 0.5% heavy bupivacaine (14 mg) (Anawin*Heavy; Neon Laboratories Limited, Palghar, Maharashtra, India)+0.2 ml normal saline.
Group 2 (n = 30) patients received 2.8 ml of intrathecal 0.5% heavy bupivacaine (14 mg)+50 mg (0.1 ml) magnesium sulfate (Magneon, 50% v/w, total volume 2 ml; Neon Laboratories Limited, Mumbai, Maharashtra, India)+0.1 ml normal saline.
Group 3 (n = 30) patients received 14 mg of intrathecal 0.5% heavy bupivacaine (2.8 ml)+100 mg (0.2 ml) of magnesium sulfate (Magneon, 50% v/w, total volume 2 ml; Neon Laboratories Limited, Mumbai, Maharashtra, India).
All patients were explained about the procedure, advantages, and risks of the procedure during the preoperative assessment carried out 1 day before surgery, and then informed consent was obtained from the patient. Patients were educated about the visual analogue scale (VAS) during the preoperative assessment. All patients were kept nil orally for at least 8 h before surgery and no premedication was administered. In the operation theater, after securing an 18-G intravenous cannula, 10 ml/kg/h infusion of 0.9% sodium chloride (NaCl) solution was started. After standard anesthesia monitoring, baseline measurements of heart rate, noninvasive arterial blood pressure, percentile oxygen saturation (SpO2), and respiratory rate were recorded.
After antiseptic skin preparation and sterile draping, lumbar puncture was performed at the level of L3–L4 vertebra with a 26-G quincke spinal needle in sitting position, and 3 ml of study drug solution was administered after confirming the free flow of cerebrospinal fluid by an anesthesiologist blinded to the group assigned and the contents of the drug injected. After placing the patient in supine position, the sensory level was assessed by means of pinprick sensation using a blunt 25-G needle along the midclavicular line bilaterally at 3, 6, 9, 12, 15, 20, 25, and 30 min, and then every 15 min. The time to reach the sensory level up to T10 dermatome and maximum sensory level and the time for two-segment regression and to S1 segment regression were recorded. The motor level was assessed according to modified Bromage scale  to know the time to reach maximum Bromage level and the time to Bromage 0 regressions.
All patients were monitored intraoperatively for systolic, diastolic, mean blood pressure, heart rate, oxygen saturation, respiratory rate every 1 min for the first 10 min, and then every 5 min for half an hour and every 15 min until the end of surgery in the operating room and also in the recovery room. Any hypotension (mean arterial pressure <70 mmHg) episode was treated with ephedrine intravenous 6 mg bolus, and episodes of bradycardia (heart rate <40 beats/min) were treated with 0.02 mg/kg of atropine intravenously. Patients were supplemented with oxygen at a rate of 4–6 l/min through oxygen mask in the intraoperative period.
Postoperatively, patients were observed for vitals and pain in the post anesthesia recovery room and then in the postsurgical ward for 24 h. Severity of pain was measured using a 10 cm VAS at hourly interval for the next 6 h after subarachnoid block and then at eighth, 10th, 12th, 15th, 18th, and 24th hour. The postoperative rescue analgesia was provided with 2 mg/kg of diclofenac sodium infusion (VAS>3), and if not controlled within 30 min then intravenous tramadol (1 mg/kg boluses) was administered. The time to request for first rescue analgesia (pain-free interval) and frequency of rescue analgesia required were noted. The primary outcome measure in this study was the duration of postoperative analgesia – that is, the time to first analgesic request from the time of performing block. The secondary outcome measures included the number of supplemental analgesic requirements, hemodynamic stability, and side effects.
Data were collected and entered in MS Excel 2010 (Microsoft Corporation, US). Statistical analysis was performed using SPSS software 17 (SPSS Inc., Chicago, Illinois, USA). The one-sample Kolmogorov–Smirnov test was used to determine whether data sets differed from a normal distribution. Normally distributed data were analyzed using repeated measures general linear model analysis of variance, whereas non-normally distributed data were analyzed using the Mann–Whitney U-test and categorical data were analyzed using the χ2-test. For comparison between two groups, the post-hoc test was applied in normally distributed data. A value of P less than 0.05 was considered significant.
A power analysis was performed to determine the necessary number of patients for each group based on duration of analgesia. With a two-sided type I error of 5% and study power at 80%, it was estimated that 25 patients would be needed in each group to detect a difference of 35 min in the duration of analgesia between the two groups. Therefore, to account for probable dropouts and block failure, we intended to enroll 90 patients in three groups.
| Results|| |
Total number of patients enrolled during the study period were 105 in three groups, and 15 patients were excluded for not meeting the inclusion criteria [Figure 1]. Therefore, we randomized 90 patients (30 in each group) comparable to each other with respect to age, sex, weight, and duration of surgery [Table 1].
In all three groups comparable median values of peak sensory level was observed (P = 0.104) [Table 2], although the mean peak sensory block was achieved earliest in group 1 (8.98 ± 2.94 min); the mean peak sensory block was 10.00 ± 2.49 min in group 2, and maximum time was taken in group 3 (10.35 ± 2.15 min). Similarly, the time taken to achieve optimum sensory block to start the surgery (T10 level) in groups 1, 2, and 3 was 4.38 ± 1.30, 5.27 ± 1.90, and 5.73 ± 1.39 min, respectively (group 1 vs. group 2: P < 0.05 and group 1 vs. group 3: P < 0.000) [Table 2].
The time taken to achieve bromage 3 was achieved in 3.52 ± 1.62, 4.12 ± 1.63, and 4.38 ± 1.22 min in groups 1, 2, and 3, respectively (group 1 vs. group 2: P < 0.01). In group 1, the mean time taken for regression of sensory block using two segments (2 Seg Reg) was earliest (63.50 ± 13.18 min), followed by group 2 (71.27 ± 14.33 min) and group 3 (85.83 ± 14.64 min) (P < 0.001; group 1 vs. group 2: P<0.001; and group 2 vs. group 3: P < 0.001) [Table 2].
Total duration of sensory block was 303.73 ± 42.99, 248.53 ± 41.33, and 208.07 ± 41.89 min (group 1 vs. group 3: P < 0.001; group 1 vs. group 2: P < 0.01; and group 2 vs. group 3: P < 0.001) in groups 1, 2, and 3, respectively. The mean time taken to achieve Bromage 0 was minimum in group 1 (157.97 ± 33.46 min) and maximum in group 3 (217.30 ± 45.31 min). In group 2, it was 163.60 ± 37.89 min (P < 0.001). On the Mann–Whitney test a significant difference was found between groups 1 and 3 (P < 0.001) and group 2 versus group 3 (P < 0.001) [Table 2]
The mean duration of analgesia [Figure 2] was maximum in group 3 (217.30 ± 45.31 min) followed by group 2 (163.60 ± 37.89 min) and minimum in group 1 (168.50 ± 31.83 min) (P = 0.000; group 1 vs. group 3: P < 0.001; group1 vs. group 2: P < 0.001; and group 2 vs. group 3: P < 0.001). The mean total dose of rescue analgesic [Figure 3] was minimum in group 3 (2.43 ± 0.63), maximum in group 1 (3.30 ± 0.79), and 2.63 ± 0.56 min in group 2 (P < 0.001; group 1 vs. group 3: P < 0.001; and group 1 vs. group 2: P < 0.01).
|Figure 2 Comparison of duration of postoperative analgesia in three groups. Values are expressed as mean ± SD. Mean analgesic duration was significantly increased in group 3 compared with groups 2 and 1 (P = 0.000).|
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|Figure 3 Comparison of mean total dose of rescue analgesic in three groups. Values are expressed as mean ± SD. Mean total demands of rescue analgesic was significantly less in group 3 compared with group 1 and group 2 (P < 0.001 and P<0.01, respectively).|
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Patients remained hemodynamically stable [Figure 4] with comparable mean heart rates, mean blood pressure, and percentile oxygen saturation in the perioperative period (P > 0.05).
|Figure 4 Comparative evaluation of hemodynamic parameter (mean blood pressure and heart rate, percentile oxygen saturation) in three groups. Values are expressed as mean ± SD. The three groups were comparable at all time intervals (P > 0.05) during the study period.|
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| Discussion|| |
In the context of ‘Augmentation strategies’ for intrathecal analgesia, the introduction of NMDA receptor antagonists is undoubtedly one of the most significant advances in pain management in the last two decades .
Magnesium sulfate is a noncompetitive antagonist to NMDA receptor and prevents central sensitization from peripheral nociceptive stimulation . The efficacy and safety of intrathecal magnesium sulfate has been reported in rats and humans in previous studies ,,. Haubold and Meltzer  concluded that intrathecal magnesium sulfate (1000–2000 mg) in humans produced spinal anesthesia, including motor and sensory block without neurological damage. In a study by Saeki et al. , the effect of intrathecal magnesium sulfate at a dose of 0.3 mg, 1, 2, and 3 mg/kg on nerves was examined in rabbits and a significant sensory dysfunction was observed in the 3 mg/kg group 7 days after administration. Thus, intrathecal magnesium sulfate has a good safety profile ,, if used at a dose less than 3 mg/kg.
In a meta-analysis published by Ramirez et al.  on effects of perineural magnesium sulfate, it has been shown that a dose of 50 to 100 mg of intrathecal magnesium could be useful when a spinal anesthetic is used. Further studies on the 100 mg dose are still needed to rule out a dose-related benefit. Keeping in mind the doses of magnesium used in various studies, we intended to compare two doses of magnesium sulfate (50 and 100 mg) as an adjuvant to intrathecal bupivacaine. In the present study, we observed comparable peak level of sensory block in all three groups.
We observed that the onset of sensory and motor block was directly related to the dose of magnesium sulfate used, and, with an increase in dose, the onset was delayed. These results were also reported by Ozalevli et al.  when adding intrathecal magnesium to fentanyl and isobaric bupivacaine and Malleeswaran et al. , who used hyperbaric bupivacaine as in the present study and both explained this delay by the difference in pH and baricity of the solution containing magnesium.
In our study, two-segment regression time was directly related to the dose of intrathecal magnesium sulfate used and correlates well with the study conducted by Khalili et al. . Motor block duration was significantly prolonged (P < 0.001) in a dose-dependent manner in the magnesium groups in the present study. There was a significant increase in the duration of analgesia in the 100 mg group as compared with the 50 mg magnesium group and the control group, and similar results were observed in studies conducted by Sayed and Fathy  and Jabalameli and Pakzadmoghadam .
Total analgesic drug consumption in 24 h was decreased in the magnesium groups compared with the control group (P < 0.001); this was also observed in study conducted by Khalili et al. . It was confirmed that total dose of analgesic required is inversely proportional to the amount of magnesium sulfate administered intrathecally.
There was no statistically significant difference in the heart rate between the groups at any intraoperative time interval (P > 0.05). No patient required treatment with atropine for bradycardia. This may be again attributed to the absence of systemic vasodilator effects of spinal magnesium . There was a significant intergroup difference in mean blood pressure at 10 min (P = 0.007). None of the patients required administration of ephedrine or additional fluids for hypotension. We did not observe a decrease in respiratory rate in three groups at all time intervals, and mean oxygen saturation remained above 98% in all three groups.
The results of our study showed that the addition of both 50 and 100 mg magnesium sulfate as an adjuvant to intrathecal bupivacaine prolongs the duration of analgesia in a dose-dependent manner and helps in reducing the demand for rescue analgesic requirements in the postoperative period. We further conclude that 100 mg magnesium sulfate as an adjuvant to bupivacaine has better therapeutic profile without significant side effects. Therefore, 100 mg magnesium may be the recommended dose as an adjuvant to intrathecal bupivacaine.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]