European Journal of Cardiovascular Medicine

Major concern as an anaesthesiologist is the ability to manage pain perioperatively. Thus, taking care of post-operative pain, helps indirectly in gaining the confidence of the patient, reduces anxiety of the patient, prevents chronic pain and also help in faster recovery.

Intra operative shivering interferes with measurement of various parameters such as HR, BP, oxygen saturation, ECG, thus making it difficult to monitor the haemodynamics of the patient which again becomes the most important criteria for the better operative outcomes of the patient. Taking the above two into consideration and in view of better recovery of the patient there is a need to study the efficacy of magnesium sulfate in managing post regional anaesthesia shivering and post-operative pain.

 The primary objectives being to study the incidence of post-anaesthetic shivering with the use of magnesium sulfate, efficacy of magnesium sulfate in reducing post-operative pain for 24 hours, comparison of the two groups (Test and the control group) in terms of postoperative pain and post anaesthetic shivering and time of rescue analgesics among both the groups. Secondary objective was to note any adverse effects.  Post-operative pain management is of utmost importance as it prevents patient discomfort, anxiety, prolonged hospital stay. 2-10% of the acute post-operative pain if not treated adequately will go into chronic post-surgical pain. (1)  Post anaesthetic shivering is the common complication of regional anesthesia due to impaired thermoregulation which inturn leads to increase in oxygen consumption, arterial hypoxemia, lactic acidosis and is specifically detrimental in cardiac patients. Intraoperative shivering interferes with monitoring of heart rate, blood pressure, electrocardiogram etc. Reported incidence of post anaesthetic shivering is 20-70%. (2)  Noxious stimuli can produce the expression of new genes in the dorsal horn of the spinal cord within 1 hour. The mechanism of neuroplasticity and progression to chronic pain has been attributed to this gene activation. The intensity of acute postoperative pain is a significant predictor of chronic postoperative pain. Various drugs are being used which act by different routes and different mechanisms, with their own set of adverse effects. Drugs such as NSAIDs, Opioids, Local anesthetics etc are widely used for the treatment of perioperative pain. The prevalence of postoperative pain is 84.17%, 92.5%, and 96.66% at the fifth post-operative hour, second, and third postoperative days, respectively. (3) The study involves a versatile drug, magnesium sulfate with the role of an anticonvulsant, tocolytic, antiarrhythmic, analgesic, etc. Magnesium is involved in adenosine 5’-triphosphate function, antagonizes NMDA glutamate receptors, inhibits catecholamine release, and is involved in the regulation of other electrolytes. The use of Magnesium sulfate for perioperative analgesia as an adjuvant is based on its properties as an NMDA receptor antagonist and calcium channel blocker. Although the basic mechanism of the analgesic effect of Mg is unclear, it is presumed that its antagonism of the NMDA receptor prevents the induction of central sensitization due to peripheral nociceptive stimulation, and abolishes hypersensitivity (4). Thus, decreasing the use of opioids. Shivering is an involuntary, oscillatory muscular activity that augments metabolic heat production. Shivering is a very unpleasant and discomforting complication ranging from mild skin eruptions to severe forms with continuous skeletal muscle contractions. the reported incidence of post-anaesthetic shivering is 20-70% (2). Intravenous magnesium has been shown to suppress postoperative shivering suggesting that the agent increases the shivering threshold. Recently, intravenous magnesium sulfate added as a part of a pharmacological anti-shivering regimen showed an increased cooling rate in unanesthetized volunteers. The drug is a mild muscle relaxant, also exerts a central effect and thus simultaneously may reduce the severity of shivering. (5) Various drugs to treat shivering include tramadol, pheniramine maleate, dexamethasone, morphine, fentanyl etc. with varied effects.

A randomized prospective single-blind case-control study conducted in 350 patients with 175 patients in each group (according to Slovin’s formula). Elective procedures in patients within the age group of 20-60 years belonging to the American Society of Anesthesiologists grade 1 and 2 and those undergoing lower abdominal and lower limb surgery under the subarachnoid block were included. Patients with severe cardiovascular and musculoskeletal disorders, history of any drug allergy, bradyarrhythmia, calcium channel blockers, renal disease, and parturients were excluded. Ethical Committee approval granted on 26/08/2020 by the Institutional Ethics Committee (DYPMCK/326/2020/IEC). Selected patients were divided into two groups by chit selection method, all even numbers were taken into the group and odd numbers were taken as control. Group M (n=175) received magnesium sulphate as an infusion and Group S(n=175) received normal saline as an infusion. The study was started after taking informed and written consent from the patients. Routine preoperative evaluation and investigations were done as per the protocol. On the day of surgery, we proceeded routinely after noting baseline parameters with a standard multipara monitor. Subarachnoid block was placed with 25 g Quincke needle using heavy bupivacaine. Infusion was prepared by the helper and the principle investigator assessing the pain and shivering was blinded. After 10 minutes of spinal anaesthesia, magnesium sulfate infusion/normal saline 5ml/hr (15mg/kg/hr) depending upon the magnesium sulfate or normal saline receiving group was started intraoperatively and continued for 6 hours. All patients received inj. Midazolam 0.05mg/Kg IV and inj. pentazocine 0.6mg/kg IV. Post-operative pain was assessed with the use of a visual Analog Score (VAS) at the 2nd,4th,6th,12th, 18th, and 24th hours. When VAS was more than 4 at any time, the attending nurse was asked to give inj.paracetamol 1gm intravenously and wait for half hour. If the VAS was still above 4 then inj.diclofenac sodium 75mg was given intramuscularly and the time of requirement of rescue analgesic noted. Postoperatively patients were assessed for shivering episodes and were treated with oxygen at 4L/min, watched for 20 minutes after which inj. Tramadol 25mg was given intravenously. If there still existed grade 2 and above shivering patient received inj. dexamethasone intravenously. VAS was used to assess pain, scoring was done with numbers from 0 to 10; 0= no pain; 1-3=mild pain;4-6=moderate pain;7-10 severe pain. (6). The time of requirement of rescue analgesic was noted. Post-anaesthetic shivering was noted anytime in recovery, and was graded using Crossley and Mahajan scale (0-4) 0=No shivering; 1=No visible muscle activity but piloerection is seen;2=muscular activity in only one muscle group; 3= Moderate muscular activity in more than one muscle but no generalized shaking; 4=Violent muscular activity that involves the whole body. (7) Sedation was evaluated before discharge from the recovery room according to a four-point rating scale- 1=Patient fully awake;2=Patient somnolent but responds to verbal commands;3=Patient somnolent but responds to tactile stimuli;4=Patient asleep but response to pain.

Results were interpreted using R Studio Software Version 1.2.5001 In this study there was comparing two groups and block randomization was used. All the categorical variables were present in the frequency distributional form. Calculation of mean and standard deviation for continuous variables were done. For finding the association between two groups here Chi- Square test was used. Also, the significant mean difference between the two groups was observed by the Two Sample Independent T-Test. Graphical Analysis is done for variables under study. The p-value less than or equal to 5% is considered significant. In this study, the mean VAS score was significant at 4 Hr., 6 Hr., 12 Hr., and 18 Hr. From the graph, we can clearly depict that, the mean VAS Score was less in the Group of Magnesium sulfate as compared to the Group of Normal Saline.

Magnesium group 63 (36.00%) had the first dose of analgesic at the 18^th hour. Followed by 46 (26.29%) who had the first rescue analgesic at the 12^th hour, and 36 (20.57%) at the 24^th hour. Similarly, in the normal saline group, 93 (53.14%) had started analgesic 6^th hour. Followed by 47 (26.86%) who had the first rescue analgesic in the 4^th hour, and 32 (18.29%) had it in the 12^th hour. The p-value of the Chi-Square test of association was 0.0000, which indicates that there was sufficient evidence to conclude that we found a significant association between the Start of Analgesic and Groups. The mean value of start analgesic in the magnesium group is 14.90 ± 7.38 and in normal the saline group is 6.70 ± 2.99. The p-value was 0.0000, which indicates a significant mean difference was found.

 In the current study, in magnesium group, 49 (28.16%) had Grade 1 shivering. Followed by 46 (26.44%) had Grading 2, 40 (22.99%) had grade 0, 21 (11.49%) had Grade 3 of Shivering.

Similarly, in the normal saline group, 87 (50.00%) had Grade 3 of Shivering. Followed by 45 (25.29%) who had Grade 2, and 32 (18.39%) had Grade 4. The p-value of the Chi-Square test of association was 0.0000, which indicates that there was sufficient evidence to conclude that. we found a significant association between Grades of Shivering and Groups.

 The mean value of grade of shivering in the magnesium group is 1.59 ± 1.26 and in the normal saline group is 2.80 ± 0.81. The p-value was 0.0000, which indicates a significant mean difference was found.

In this study magnesium group, 57 (32.76%) had Sedation Score of 3. Followed by 48 (27.59%) had Sedation Score 1, 43 (24.14%) Sedation Score 2, 27 (15.52%) had Sedation Score 4. Similarly, in the normal saline group, 85 (48.85%) had a Sedation Score of 2. Followed by 71 (40.23%) who had Sedation Score 1, and 19 (10.92%) who had Sedation Score 3. The p- value of the Chi-Square test of association was 0.0000, which indicates that there is sufficient evidence to conclude that we found a significant association between Sedation Score and Groups. The mean value of start analgesic in the magnesium group is 2.36 ± 1.05 and in the normal saline group is 1.71 ± 0.65. The p-value was 0.0000, which indicates a significant mean difference was found.

Fig.1: Comparison of VAS Score among both groups.

Fig.2: Comparison of the start of analgesic in both the groups.

Fig.3: Comparison of grades of shivering in two groups.

Fig.4: Comparison of Sedation Score among Two Groups.

TABLES

Table 1: Comparison of VAS scores among both groups.

Table 2: Comparison of grades of shivering in two groups.

Depending upon of pathophysiology of pain, the importance of proper and timely management of postoperative pain has improved patient outcomes and early recovery. Studies where in dose with initial IV bolus followed by IV infusions are there. Thus, we opted for the minimal infusion dose of 15mg/kg/hr without a bolus dose. As spinal anesthesia also causes a drop in blood pressure initially we avoided IV bolus of magnesium sulfate. When provided on basis of preventive analgesia it helps to counteract the development of chronic pain. Shivering continues to be a common problem faced during intraoperative and postoperative problem faced during both regional and general anesthesia. Shivering is a very unpleasant experience for patients, it increases oxygen consumption and also interferes with routine monitoring like ECG, pulse oximetry, and BP, and also causes tension on suture lines.

It is detrimental to patients with low cardiorespiratory reserve. It is uncomfortable to the patients as well as to the operating room personnel mostly during regional anesthesia. (8–11) In this study we have analysed the use of Magnesium sulfate infusion in postoperative pain and post-anesthetic shivering under spinal anesthesia. VAS was assessed at the 2nd hour there was no significant statistical difference between both the groups as the action of spinal anesthesia mostly had not weaned off. When assessed VAS at the 4th,6th,12th, and 18th hour, the pain was significantly less with VAS less than 4 in the group which received magnesium, and in those who received normal saline when the VAS was more than 4 received a rescue analgesic which helped in a decrease in VAS. The mean VAS at the 4th hour was 2.89 in those who received magnesium and 3.90 in those who received normal saline. At the 6th - hour means VAS in those who received magnesium was 3.28 and 4.83 in those on normal saline. At the 12th hour VAS in the magnesium group was 3.96 and in the normal saline group was 4.78. At the 18th hour, VAS in the magnesium group was 4.52 and the normal saline group was 4.62. At the 24th hour VAS in the magnesium group was 4.52 and in the normal saline was 4.62 This clearly depicted that the mean VAS score was significantly less in the magnesium group when compared to the normal saline group. Start of rescue analgesic: No patients from both groups received rescue analgesics at the 4th hour whereas, 47 patients from the normal saline group received the first dose of rescue analgesic. From the normal saline group, patients mostly received their first rescue dose at the 6th hour and those who received Mgso4 received their first dose from the 12th to 18th hour. 22 patients from the study group ie receiving magnesium sulfate had no requirement of analgesics up to 24 hours. no patients at the 24th hour and only 3 patients from the 18th hour required rescue analgesia from the normal saline group as they had already received the rescue analgesic earlier and their VAS was less than 4 due to the previous rescue analgesic. Thus, 36% of the patients from the study group the required first rescue analgesic at the 18th hour, and 53.14% of patients from the normal saline group received the first rescue analgesic at the 6th hour. Hence, there is statistical significance among both groups according to the first dose of rescue analgesic received.

Grades of shivering: Shivering was graded according to the Crossley and Mahajan scales. In those who received an infusion of magnesium sulfate, most of them experienced a grade of 0- 2 shivering, and those who received normal saline experienced a grade of 2-4 shivering.

26.44% of patients in the study group had a grade 2 of shivering and 50% of patients in the control group had a grade 3 of shivering.

Sedation score: Sedation was assessed according to the four-point sedation scale. All patients  received routine sedation with inj. Midazolam 0.05mg/Kg IV and inj. Pentazocine 0.6mg/kg IV along with the magnesium sulfate/ normal saline infusion. 32.76% of patients in the

magnesium group had a sedation score of 3 and 48.85% of those who received normal saline

had a sedation score of 2. No patients from the control group had a sedation score of 4, whereas

27 patients from the study group had a sedation score of 4. In 2010 J-Y Hwang et al studied

Forty patients undergoing total hip replacement arthroplasty under spinal anaesthesia for the

requirement of postoperative analgesia and incidence of shivering. Magnesium 50 mg/ kg for

15 min and then 15 mg/ kg/ h by continuous i.v. infusion until the end of surgery was given to

the test group. The saline group (Group S) received the same volume of saline over the same

period, from which they concluded that I.V. magnesium sulphate administered during spinal

anaesthesia improves postoperative analgesia (4). Aslan B et al 2018 studied the efficacy of

prophylactic magnesium infusion in decreasing shivering and extending the duration of

analgesia in caesarean sections under spinal anesthesia among 80 patients. 10 mg/kg bolus

followed by 500 mg/hour magnesium sulphate was administered to Group M for 24 hours.

Group R received only Ringer Lactate i.v infusion. Group R and Group M received 10 ml/kg of Ringer’s lactate during intraoperative. In the first 24 hours: shivering, the first pain sensation,

motor block withdrawal period, and analgesic requirement of the groups were evaluated, also 6-hour sedative and visual analog scores and concluded that a significant decrease in consumption of analgesics over 6 hours and VAS was significantly less among the group which received magnesium sulfate infusion (12). Our study has shown that infusion of magnesium sulfate intraoperatively has decreased post-operative pain and the requirement of opioids for up to 24 hours. Also, the incidence of higher grades of shivering was comparatively less in those who received magnesium infusion.

We can conclude that magnesium sulfate when given as a low dose infusion intraoperatively and immediate postoperative period is effective in prolonging the duration of analgesia and in decreasing the incidence of post-anesthetic shivering in patients undergoing surgery under spinal anesthesia.

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