European Journal of Cardiovascular Medicine

Pain is an uncomfortable sensation that arises from current or potential tissue injury. Epidural administration is a reliable and effective method for delivering surgical anesthesia and pain relief after surgery. No medication has been found that can specifically block nociception without causing side effects. Neuraxial adjuvants are utilized to enhance or prolong pain relief. These have been used to extend postoperative pain relief in conjunction with spinal anesthesia [1]. Still, because epidural anesthesia is more hemodynamically stable, the addition of adjuvants will have a significantly less adverse impact. Various agents, including dexmedetomidine, a selective alpha-2 adrenergic receptor agonist, and magnesium sulfate, can serve as adjuvants in neuraxial anesthesia alongside local anesthetics [1,2,3]. Regional anesthesia also provides the advantage of postoperative pain relief, which is the most sought-after benefit by patients. It can decrease or eliminate the risks and discomfort associated with general anesthesia, such as sore throat, airway injury, and muscle pain. Additionally, it presents several benefits for outpatients undergoing surgical procedures.

EPudural anaesthesia is the most widely used method for providing both anaesthesia and postoperative pain relief for surgical patients [4]. The key goals of modern surgical practices include facilitating early postoperative mobility, promoting rehabilitation, and ensuring minimal pain and discomfort [5-7]. The preferred medications in this context

are local anaesthetics such as bupivacaine and lignocaine, which can be used with or without adrenaline [7,8]. Historically, opioid medications like fentanyl, morphine, and buprenorphine have been used as adjuvants; however, they can lead to side effects such as itching, urinary retention, nausea, vomiting, and respiratory depression [9-11]. Alpha-2 agonists represent one of several new classes of adjuvants for local anaesthetics currently undergoing investigation. These adjuvants exhibit outstanding analgesic properties and function by enhancing the effects of local anaesthetics, a process that is mediated through the hyperpolarization of nerve tissues by altering the transmembrane potential and ion conductance at the locus coeruleus in the brainstem [12].

Another class of drugs used as an adjunct is magnesium sulphate. The pain-relieving properties of epidural Magnesium Sulphate (MgSO4) arise from its non-competitive antagonism of the N-methyl-D-aspartate (NMDA) receptor [13]. Recent research indicates the potential of magnesium sulphate as an adjunct to local anesthetics in spinal anesthesia [14].

In the aforementioned studies, dexmedetomidine and magnesium sulfate were assessed as adjuncts to 0.5% bupivacaine for surgical anesthesia. There have not been any studies that directly compared a single epidural bolus dose of magnesium sulfate at 50 mg and dexmedetomidine at 0.5 mcg/kg with 0.125% bupivacaine regarding the duration of postoperative pain relief. Therefore, this current study was initiated to evaluate the hemodynamic parameters, analgesic effects, and complications during the post-operative phase.

OBJECTIVES

1. To evaluate and compare hemodynamic parameters including heart rate (HR), mean arterial pressure (MAP), respiratory parameters including rate (RR) and SPO2 with epidural magnesium sulfate vs dexmedetomidine vs normal saline during the postoperative period.
2. To compare the duration of postoperative analgesia.
3. To compare the incidence of postoperative complications including nausea, vomiting, respiratory depression, pruritus, hypotension, bradycardia and sedation.

Study Design: Prospective, randomized open-label study. 

Study area: The study was conducted in the Department of Anaesthesia, Subbaiah Institute of Medical Sciences and Research Centre, Shivamogga. 

Study Period: 1 year.

Sample size: The Study consisted of a total of 90 subjects.

A total of 90 patients belonging to the American Society of Anesthesiologists (ASA) grade I or II were included in the study. Patients were randomly allocated into three groups to receive either 1ml of 50mg/ml magnesium sulphate (group M; n = 30), or dexmedetomidine 0.5microgram/kg (group D; n = 30) or 1ml of normal saline (group C) in 10 ml epidural anaesthetic solution(9ml 0.125% bupivacaine) given slowly over 10-15 minutes with haemodynamic monitoring.

Sampling Technique:  Simple Random technique.

Inclusion Criteria:

1. patients undergoing elective lower abdominal surgeries under epidural anaesthesia
2. Surgery lasting less than 120 min
3. age group between 20 and 55 years, and

ASA I and ASA II.

Exclusion criteria:

Patients with a history of convulsions and multiple allergies, with major system illnesses, pregnant and lactating women and those having contraindications for epidural block were excluded from the study. Patients with a history of adverse reaction to any study medication, history of analgesic use, and chronic pain syndrome, where communication difficulties preventing reliable assessment and patients for whom central neuraxial block is contraindicated.

Ethical consideration: Institutional Ethical committee permission was taken before the commencement of the study.

Study tools and Data collection procedure:

GROUPS:

Patients were randomly divided into 3 groups of 30 each.

GROUP (M): 1 ml of 50mg/ml magnesium sulphate in 9ml 0.125% bupivacaine.

GROUP (D): dexmedetomidine 0.5 mcg/kg in 9ml 0.125% bupivacaine.

GROUP(C): 1 ml of normal saline in 9ml 0.125% bupivacaine.

All patients were premedicated with oral alprazolam 0.25 mg and ranitidine 150 mg 2hbefore surgery. Visual analogue pain scale (VAS: 0: no pain, 10: worst pain ever)( and sedation was graded by five point scale (1-alert and wide awake, 2- arousable to verbal command, 3-arousable with gentle tactile stimulation, 4- arousable with vigorous shaking, and 5-unarousable) was explained to the patients before the operation. Standard monitors were applied in all the patients. After i.v. Access had been established, and an infusion of crystalloid commenced; all patients received epidural anaesthesia. The epidural space was identified at L3–4 or L4– 5 using a loss-of-resistance to air technique, and an epidural catheter was then advanced for 3-4cm into the epidural space. Epidural anaesthesia was instituted with 0.5%bupivacaine through the catheter to achieve a block above the T8 level. The sensory block was assessed bilaterally by using analgesia to pinprick. When surgery was complete, the patients were randomly allocated into three groups using computer generated randomization to receive 1 ml of 50mg/ml magnesium sulphate (group M) or dexmedetomidine 0.5mcg/kg(group D) or 1 ml of normal saline ( group C) in 10 ml epidural anaesthetic solution (9 ml 0.125%bupivacaine) given slowly over 10 – 15’ minutes with haemodynamic monitoring. The analgesic regimen was prepared by the anaesthesiologist managing the patient, who was not subsequently involved in data collection. It was commenced in the recovery room while the block was still effective. Patients and nursing staff were also blinded to the group randomization. Hypotension was defined as a 20% decrease from baseline and was treated with an i.v. Fluid bolus of 500 ml of lactated Ringer’s solution followed by i.v. mephenteramine 6 mg if required. In the postoperative period respiratory rate(RR), heart rate  (HR), systolic blood pressure(SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) were monitored at 0 min, and then at 30min,1, 2, 4, 8, 12, and 24h. Postoperative pain and sedation were assessed using VAS scoring and a sedation five-point scale at 0, 1, 2, 4, 8, 12, and 24 hours. A resting VAS score <3 It was considered satisfactory. If patients had inadequate analgesia (VAS > 3), epidural fentanyl 1mcg/kg in 10ml normal saline was administered as supplementary rescue analgesic. The duration of analgesia and total consumption of opioids were evaluated. Adverse events related to the drugs (drowsiness, respiratory depression, nausea, vomiting, pruritus, hypotension, bradycardia and sedation) and epidural catheter were recorded throughout the 24 hr study period. All patients enrolled in the study were thoroughly evaluated for any neurological or systemic toxicity at the time of discharge and were instructed to report back in case of any complication.

STASTICAL ANALYSIS:

The duration of postoperative analgesia, hemodynamic parameters and complications with different medications were analyzed statistically. A study population of 30 patients for each group was determined. The data were expressed as mean+/- standard deviation (SD). Statistical analysis of data among the group was done by ANOVA test.

In the present study, the Mean Age of patients who received Dexmeditomidine was 47.07±4.50 Years, the Mean Age of patients who received Magnesium was 46.8±4.07 Years, and the Mean Age of patients in the control group was 46.57±4.58 Years, and this difference was found to be statistically not significant.

In this study, the Mean Height of patients who received Dexmedetomidine was 151.53±26.93cms, the Mean Height of patients who received Magnesium was 158±5.58 cms, and the Mean Height of patients in the control group was 155.27±5.05 cms, and this difference was found to be statistically not significant.

In this study, the Mean Weight of patients who received Dexmedetomidine was 53.67±4.23 Kgs, the Mean Weight of patients who received Magnesium was 53.67±4.02 Kgs, and the Mean Weight of patients in the control group was 53.33±4.16 Kgs, and this difference was found to be statistically not significant.

In the present study, the Mean duration of surgery of patients who received Dexmedetomidine was high at 108.3±9.23 minutes when compared to the Mean duration of surgery of patients who received Magnesium at 105.93±8.74minutes and the Mean duration of surgery of patients in the control group was 108.17±9.33minutes but this difference was found to be statistically not significant.

Table 1: Distribution of study participants based on Duration of Analgesia

The Mean duration of analgesia of patients who received Dexmedetomidine was high 395.13±61.66minutess when compared to the Mean duration of analgesia of patients who received Magnesium, which was 281.87±26.04minutes, and the Mean duration of analgesia of patients in the control group was 199.13±8.49minutes, and this difference was found to be statistically significant.

In the present study, based on the number of fentanyl doses given, the Mean of patients who received Dexmedetomidine was 2.27±0.45, the Mean of patients who received Magnesium was 3.07±0.25, and the Mean of patients in the control group was 4.47±0.50, and this difference was found to be statistically significant.

In the present study, based on total fentanyl consumption, the Mean of patients who received Dexmedetomidine was 119.77±23.69, the Mean of patients who received Magnesium was 169.57±17.64, and the Mean of patients in the control group was 169.57±17.64and this difference was found to be statistically significant.

       Table 2: Distribution of study participants for Heart Rate at Different Time Intervals Vs Three Groups.

In this study the mean Heart rate in patients who received Dexmedetomidine has better control over in patients who received Magnesium and patients in control group and this difference observed was statistically significant at the hours, 4hrs, 8hrs, 12hrs and 24hrs though at the beginning (0mint,30min,1hr) it is not statistically significant.

      Table 3: Distribution of study participants for Mean Arterial Pressure at Different time intervals vs. three Groups.

The Mean Arterial pressure was initially high who received Dexmedetomidine at pre operatively later on dip at LMA insertion and during the time frame this group has lesser Mean Arterial pressure compared to those who received Magnesium and patients in control group and this difference is statistically significant initially but later on at the 8hr, 12hr, 24hrs it was not statistically significant.

   Table 4: Distribution of study participants for SPO2 at Different time intervals vs. three Groups.

The saturation remained nearly similar at all-time intervals with Dexmedetomidine, the Magnesium group and patients who were in the control group.

           Table 5: Distribution of study participants for VAS Scores at Different time intervals Vs Three Groups.

In the present study the mean VAS Scores in patients who received Dexmedetomidine has better score over in patients who received Magnesium and patients in control group and this difference observed was statistically significant at the 1hr, 2hrs, 4hrs, 8hrs, 12hrs and 24hrs though at the beginning (0mint,30min,) it is not statistically significant.

    Table 6: Distribution of study participants for Sedation Scores at Different time intervals vs. three Groups.

The mean Sedation Scores in patients who received Dexmedetomidine were better score over in patients who received Magnesium and patients in the control group and this difference observed was statistically significant at the 1hr, 2hrs, 4hrs, 8hrs, 12hrs and 24hrs though at the beginning (0mint,30min,) it is not statistically significant.

          Table 7: Distribution of study participants based on Complications

In the present study, Pruritus was the common complication in all three groups, followed by nausea and shivering. Sedation was the most common complication due to Dexmeditomidine.

In the present study, patients were comparable concerning their demographic profile, i.e., age, gender, and weight. Baseline cardiorespiratory parameters were comparable between the study groups. In the present study, the Mean Age of patients who received Dexmeditomidine, the Mean Age of patients who received Magnesium and the Mean Age of patients in the control group were found to be statistically not significant. The Mean Height of patients who received Dexmedetomidine, the Mean Height of patients who received Magnesium and the Mean Height of patients in the control group were found to be statistically not significant. The Mean Weight of patients who received dexmedetomidine, the Mean Weight of patients who

received Magnesium and the Mean Weight of patients in the control group were found to be statistically not significant. The Mean duration of surgery of patients who received Dexmedetomidine was higher when compared to the Mean duration of surgery of patients who received magnesium sulfate and the Mean duration of surgery of patients in the control group, but this difference was found to be statistically not significant.

In the present study, we observed non-significant change in mean arterial pressure, respiratory rate and oxygen saturation from baseline values during the operative period. There was a significant change in mean heart rate (p≤0.001) between Group BM, Group BD and group C. The decrease in heart rate in the dexmedetomiine group caused by α2 agonist can be explained based on their central action by decreasing sympathetic outflow and norepinephrine release. The present study was in agreement with the study conducted by Ashraf M. Eskandar et al.. (15), which compared the Effects of epidural dexmedetomidine and low-volume bupivacaine on postoperative analgesia after total knee replacement. The demographic data were comparable in both groups. The visual analogue scale of pain showed a significant reduction between the two groups at both rest and movement, Sedation scores were significantly higher in group D compared with group B. Heart rate was significantly reduced in group D from 18 h postoperative until the end of the study. This study was comparable with the present study.

Akin S et al.. (16) conducted a study on 60 ICU patients aged >70 years undergoing abdominal surgery to assess the effectiveness and tolerability of IV administration of dexmedetomidine as an adjunct to a low-dose epidural bupivacaine infusion for postoperative analgesia, noted that significant decrease in the MAP heart rate and more sedation. This study was comparable with the present study. Divya Jain et al.. (17) conducted a randomized controlled trial to evaluate the perioperative effect of epidural dexmedetomidine in conjunction with intrathecal bupivacaine. In this trial, 60 male patients of American Society of Anesthesiologists’ grades I and II, between 20 and 50 years of age, and posted for elective lower limb orthopaedic surgery, were selected. There was a significant fall in the pulse rate and mean arterial pressure five minutes following epidural dexmedetomidine in Group II patients, which lasted throughout the study period. This study is in agreement with the present study.

In the present study, The Mean duration of analgesia of patients who received Dexmedetomidine was high at 395.13±61.66 minutes when compared to the Mean duration of analgesia of patients who received Magnesium was 281.87±26.04 minutes and the Mean duration of analgesia of patients in control group was 199.13±8.49 minutes and this difference was found to be statistically significant. The present study was in agreement with Akin S et al.. (16), who conducted a study to assess the effectiveness and tolerability of IV administration of dexmedetomidine as an adjunct to a low-dose epidural bupivacaine infusion for postoperative analgesia. Significantly more patients in the dexmedetomidine group rated their satisfaction with postoperative pain control as excellent compared with the control group, and the mean duration of analgesia was higher in dexmedetomidine compared to the control group.

In the present study the mean VAS Scores in patients who received Dexmedetomidine has better score over in patients who received Magnesium and patients in control group and this difference observed was statistically significant at the 1hr, 2hrs, 4hrs, 8hrs, 12hrs and 24hrs though at the beginning (0mint,30min,) it is not statistically significant.

The present study result is in agreement with a study conducted by Ashraf M. Eskandar et al.(15). In their study, they compared the Effects of epidural dexmedetomidine and low-volume bupivacaine on postoperative analgesia after total knee replacement. The demographic data were comparable in both groups. The visual analogue scale of pain showed a significant reduction between the two groups at both rest and movement. Arup Ghosh et al. (18) conducted A study to compare Intravenous infusion of magnesium sulphate and dexmedetomidine during SAB and noted that the Postoperative VAS score and total requirement of diclofenac was lower in the dexmedetomidine group. This study's results are similar to the present study.

In the present study The mean Sedation Scores in patients who received Dexmedetomidine has better score over in patients who received Magnesium and patients in control group and this difference observed was statistically significant at the 1hr, 2hrs, 4hrs, 8hrs, 12hrs and 24hrs though at the beginning (0mint,30min,) it is not statistically significant. The present study result is in agreement with a study conducted by Arup Ghosh et al. (18) to compare postoperative analgesia in dexmedetomidine versus magnesium sulfate pretreated patients undergoing elective infra-umbilical surgery under subarachnoid block on Seventy-four American Society of Anaesthesiologist grade I-II patients, aged 18-65 years old of either sex. And concluded that Depth of sedation was higher in group-D compared to the magnesium group.

In the present study, Pruritus was the common complication in all three groups, followed by nausea and shivering. Sedation was the most common complication due to Dexmeditomidine. Singh VP et al. (19) conducted A prospective, randomized, double-blind, controlled study on 80 adult patients 18 -58 years of age of ASA grade I/II undergoing infraumbilical surgeries to evaluate the efficacy and safety of dexmedetomidine as an adjuvant to epidural 0.75% ropivacaine. The authors concluded that Dexmedetomidine is an effective adjuvant with ropivacaine for epidural block as it prolongs the duration of motor block and analgesia with adequate sedation and minimal side effects. This study supports the present study. Kumar Paswan A et al. (20) conducted a Comparative Study of Epidural Dexmedetomidine and Magnesium Sulphate used as an Adjuvant to Ropivacaine for Post-Operative Analgesia in thoracotomy concluded that the Incidence of nausea and vomiting and respiratory depression were similar in both groups, results comparable with the present study.

The present study is in agreement with a study conducted by Ahmed M. ELbadawy et al. (21), A Comparative study of intra-articular dexmedetomidine versus ketamine as adjuvant analgesics after knee arthroscopy. They concluded that intra-articular bupivacaine/dexmedetomidine. provides better analgesia compared to bupivacaine/ketamine, and both are superior to bupivacaine alone following knee arthroscopy with minimal post-operative complication.

In this study, dexmedetomidine (0.5 mcg/kg) with 0.125% bupivacaine provided better postoperative analgesia compared to magnesium sulfate (50mg/ml) with 0.125% bupivacaine, offering longer analgesia duration and stable hemodynamics. The dexmedetomidine group had delayed first epidural top-up, fewer complications, and more sedation. Pruritus, nausea, and shivering were common in all groups. Dexmedetomidine is a safer, more effective adjuvant to bupivacaine than magnesium sulfate. Limitations include a 24-hour observation period and a gender-specific, surgery-specific (hysterectomies) study population.

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