European Journal of Cardiovascular Medicine

Spine surgery is a complex and often challenging surgical procedure accompanied with moderate to severe postprocedural tenderness. Thus, ample post surgical analgesia is crucial for faster recovery, early ambulation, reduced complications, and improved overall patient satisfaction.

Classically, acute perioperative pain management has focused on the central mechanisms underlying the sensation of pain through the use of opioid medications. However, the widespread use of opioids has reached its peak worldwide, leading to concerns about their potential for abuse, addiction, and adverse effects ^[1].

The present day hypothesis of "preemptive" analgesia suggests that analgesic approaches delivered prior to surgical incision or stimuli can change the peripheral and central nervous system workup of noxious stimuli, hence reducing central sensitization, hyperalgesia, and allodynia; however, this field needs to be explored further ^[2].

In addition, pre-emptive analgesia provides shielding to the nociceptive pathways, has the potential to lessen immediate postoperative agony, henceforth the origination of chronic pain. Interventions initiated earlier than noxious stimuli prove to be more fruitful than similar strategies applied post surgery ^[3;4].

One promising agent in this field is magnesium (Mg), an antagonist of N-methyl-D-aspartate (NMDA) receptors having tranquillising properties. Mg has now been widely accepted for intra and postoperative pain relief as an adjuvant.

The combination of different analgesic modalities, such as low-dose opioids, local anaesthetics and non-steroidal anti-inflammatory drugs (NSAIDs) along with magnesium sulfate (MgSO₄) has achieved effective pain relief while cutting down the side effects associated with individual agents ^[5]. Administration of intraoperative intravenous MgSO₄ in patients undergoing major spine surgeries can potentially lead to the following benefits ^[6] :

• Alleviation in postoperative pain intensity and opioid consumption
• Attenuation of central sensitization and hyperalgesia
• Decreased inflammatory response and associated pain
• Improved hemodynamic stability and reduced stress response
• Enhanced patient comfort and early mobilization during the postoperative period

Mg has also been reported to have neuroprotective properties ^[7;8] with respect to spinal cord and nerve root manipulation during spine surgeries. It prevents neuronal injury and minimizes establishment of persistent pain by attenuating the excitotoxic effects of glutamate and other neurotransmitters ^[9]. Thus, by exploring strategies such as the use of MgSO₄ as an intraoperative agent, we hope to advance the field of perioperative pain management and improve the standards of care for the individuals undergoing major spine surgeries.

INFORMED CONSENT: Informed written consent was signed by all the participants before the conduct of this study.

STUDY DESIGN AND SETTING: This prospective, randomized, double-blind study was conducted at the Department of Anaesthesia, Mahatma Gandhi Medical College, Jaipur from September 2022 to February 2024. The study was conducted in strict compliance with the principles of the Declaration of Helsinki. Approval was obtained from the Ethics Committee of Mahatma Gandhi University of Medical Science & Technology (MGUMST), Mahatma Gandhi Medical College and Hospital, Jaipur [Approval number: MGMC&H/IEC/2022/1000]. Study is registered with the Clinical Trials Registry of India [CTRI/2023/05/052482].

SAMPLE SIZE: Hundred consenting patients satisfying the inclusion criteria posted for major spinal surgeries. Randomization was achieved utilising the computer box system.

Group M patients (Magnesium Sulfate Group): 50 patients who received intravenous (i.v.) MgSO₄.

Group C patients (Control Group): 50 patients who received isotonic saline of 0.9%.

INCLUSION CRITERIA:

Age 18–65 years scheduled for major spine surgeries

• ASA grade I, II
• All genders

EXCLUSION CRITERIA:

• Participants having allergy to study drugs
• Patients already on opioids and other analgesics for chronic pain
• Impaired renal, hepatic function
• Patients on calcium channel blockers or Mg
• Surgery duration >5 h to avoid excessive drug infusion

PROCEDURE:

After all the required investigations, PAC was conducted a day before the surgery. Each participant received standard monitoring for ECG (electrocardiography), HR (heart rate), oxygen saturation of blood (SpO2), and non-invasive blood pressure (NIBP) and an intravenous access was established.

Group M received i.v. 20 mg/kg MgSO₄ over a 15 min period prior to induction of anesthesia and 20 mg/kg/h i.v. infusion continuously till the completion of surgery.

Group C received i.v. 0.9% isotonic saline in the same volume as the test drug.

Preparation of drugs was carried out by an anesthesiologist who was involved in neither the observation nor data collection.

A standard anesthesia induction protocol was applied intravenously with 0.004 mg/kg glycopyrrolate, 2 mcg/kg fentanyl, 2 mg/kg propofol, and 0.2 mg/kg atracurium to enable endotracheal intubation. Then, anesthesia was maintained with 50% air & oxygen mixture, isoflurane was calibrated adequately.

Hemodynamic parameters were recorded every half an hour till the termination of surgery.

Low blood pressure i.e. mean blood pressure value <65 mmHg, was encountered with boluses of 6 mg/mL Mephentermine intravenously. If postoperative analgesic protocol revealed an NRS score <6, delt with Tramadol 50 mg i.v. and NRS score >6 with Tramadol 100 mg i.v. (upon patient request).

Ondansetron 4 mg i.v. was used to treat nausea/vomiting (PONV). Postoperative pain was assessed by NRS upon emergence from anesthesia and at 2h, 4h, 6h, 12h, and 24h in the study interval.

First analgesic dose request and total analgesic used postoperatively were recorded. Episodes of PONV were recorded at emergence and thereafter at various intervals.

Finally, patients' global satisfaction was assessed 24 hours post-surgery on a five-grade scale (1=very much uncomfortable and 5=completely satisfied ).

STATISTICAL ANALYSES OF DATA:

The data were entered into Microsoft Excel after preparing a master chart. Data analysis was carried out using licensed SPSS software version 21.0 (Chicago, IL, USA). Chi-square test was used to compare categorical variables, and unpaired t-test was used for continuous variables. A p-value <0.05 was considered statistically significant.

Comparison of the mean age of the study participants, distribution according to gender, comorbidities, type of surgery, duration of surgery, i.v. fluid requirement, intraoperative vitals MAP, HR (Figure 1, 2 respectively) and postoperative nausea vomiting [PONV] (Figure 3), among Groups C and M did not differ significantly.

The total dose of intraoperative i.v. fentanyl (i.v. analgesia) of the study participants in group C and M was 128.5±17.5 and 119.0±18.6 μg, respectively. This difference was found to be statistically significant  with a p-value of 0.010 (Figure 4). Comparison of the total dose of atracurium (mg) between the two groups C and M, 67.0±5.1 mg and  59.1±5.0 mg, respectively, indicated a statistically significant difference with p-value=0.0001 (Figure 5); A Statistically  significant High NRS pain score (Figure 6) and high post-op Opioid requirement (Figure 7)  was found  in  group C compared  to group M  at  each time interval  (2h, 4h, 6h, 12h, 24h)  with a  p-value of 0.001 in both. The Overall Patient  satisfaction score of the study  participants in  group  C  and  M  was 2.46±0.65  and 3.8±0.40  respectively  which was statistically  significant  with p value of 0.0001.

Figure 1: Comparison of mean arterial pressure (MAP) at different time intervals between the two groups.

Figure 2: Comparison of heart rate (HR) at different time intervals between the two groups.

Figure 3: Comparison of postoperative nausea at different time intervals between the two groups.

Figure 4: Comparison of total dose of i.v. analgesia (μg) between the two groups during mean surgical duration of 2.2±0.6 h.

Figure 5: Comparison of total dose of atracurium (mg) between the two groups during mean surgical duration of 2.2±0.6 h.

Figure 6: Comparison of postoperative numerical rating scale (NRS) for pain at different time intervals between the two groups.

Figure 7: Comparison of postoperative opioid requirement at various time intervals between the two groups

Postoperative pain management remains a striking trial in patients undergoing major spine surgeries. Proficient pain control is crucial for patient comfort, reduction of postoperative complications, and enhanced recovery ^[10,11]. Traditional analgesic approaches, including opioids are often associated with undesirable effects such as respiratory supression, nausea and opioid dependence. Therefore, there is sprouting fascination in multimodal analgesia strategies that minimize opioid use while providing effective pain relief.

The perioperative administration of MgSO₄ has been studied over in several surgical settings, including abdominal, cardiac and orthopedic surgeries ^[12]. In these settings, Mg has shown promising sequel in reducing postoperative pain scores, decreasing opioid consumption, and improving overall patient satisfaction. However, its specific usage in major spine surgeries is less well-documented. Due to their invasive nature and extended recovery period, major spine surgeries present a unique challenge for pain management. The current study is in pursuit of insights into the benefits of MgSO₄ as part of a multimodal pain control strategy in spine surgeries.

The results couldn't find any statistically significant dissimilarities in the hemodynamic parameters admist the study groups at any of the observed intervals. The previously reported results by Sawant et al ^[13] are analogous with these conclusions. The stability of the hemodynamic parameters across different groups indicates that MgSO₄ intervention was well-tolerated and did not pose a significant risk of cardiovascular or respiratory compromise ^[14].

Peng et al ^[15] and Guo et al. documented that perioperative intravenous Mg administration could remarkably decrease postoperative ache and analgesic utilisation in patients undertaking orthopedic and other surgeries.

Kizilcik and Koner ^[16] concluded that the use of perioperative MgSO₄ in patients undergoing sleeve gastrectomy operations reduced postoperative discomfort and opioid consumption in obese patients.

The present findings are consistent with those across studies and highlight the efficiency of MgSO₄ in reducing postoperative pangs in various surgical settings, including major spine surgeries.

This was a randomised controlled, double blinded prospective study which demonstrated that the Magnesium Sulphate group (Group M) consistently reported significantly lower pain scores on the Numerical Rating Scale (NRS) in contrast to the Control group (Group C) at each the measured slot of time (2, 4, 6, 12, and 24 hours) in the postoperative period.

Furthermore, the Magnesium Sulphate group (Group M) had a statistically significant lower postoperative opioid (IV analgesia) requirement compared to the Control group (Group C) at all the measured time intervals. These results are congruous with the findings reported in several other studies that have investigated the opioid-sparing and analgesic effects of perioperative magnesium administration in various surgical settings.The study also found no significant differences in the hemodynamic parameters. This advocates that the administration of magnesium sulphate was well tolerated and did not pose a risk of hemodynamic instability.

LIMITATIONS

1. Single-center study: This research was performed at one healthcare facility, which might restrict the broad applicability of the conclusions to the diverse populations and healthcare setups.
2. Relatively small study sample: The study comprised of 50 participants in either group, which might affect the probability of detecting the subtle differences among the groups.
3. Lack of long-term follow-up: The study did not assess the long-term denoument or potential inadvertent effects related to the use of MgSO₄.

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