European Journal of Cardiovascular Medicine

Lumbar spine surgeries, integral to managing various spinal disorders, are associated with significant postoperative pain, which can impede patient recovery and rehabilitation. Effective management of this pain is paramount to facilitate early mobilization and discharge, thereby enhancing overall patient outcomes and satisfaction. Postoperative pain management remains a complex challenge, often requiring a multimodal analgesic strategy to achieve optimal results.^1,2

Among the various strategies employed, local infiltration of anesthetics at the surgical site has garnered attention for its efficacy in reducing immediate postoperative pain. Bupivacaine, a widely used local anesthetic, provides prolonged analgesic effects but its enhancement with adjuvants has been explored to further improve its analgesic profile. Adjuvants such as magnesium sulfate and dexamethasone are investigated for their potential synergistic effects when combined with bupivacaine.^3,4,5

Magnesium sulfate, acting as an N-methyl-D-aspartate (NMDA) receptor antagonist, not only reduces anesthetic and analgesic requirements but also has been demonstrated to attenuate pain following lumbar laminectomy surgeries. Its role in pain management is hypothesized to be through the modulation of calcium influx into neuronal cells, which reduces neuronal excitability and the transmission of pain signals.^6,7,8

On the other hand, dexamethasone, a potent glucocorticoid with anti-inflammatory properties, has been shown to significantly decrease postoperative discomfort by reducing inflammation at the site of tissue injury. Its long half-life and powerful anti-inflammatory capabilities make it an attractive adjuvant in multimodal analgesic protocols. Furthermore, dexamethasone may enhance the pain relief duration when used in conjunction with local anesthetics, potentially delaying the onset of pain post-surgery.⁹

Despite the prevalent use of these adjuvants in clinical settings, comparative studies on their effectiveness when combined with bupivacaine for lumbar spine surgeries are scarce. This study aims to fill this gap by conducting a randomized double-blinded trial to assess and compare the efficacy and safety of bupivacaine combined with either magnesium sulfate or dexamethasone for postoperative analgesia in lumbar spine surgeries. The investigation will focus on the analgesic effectiveness, duration of pain relief, and any adverse effects associated with each combination, providing a clear insight into their clinical applicability and potential as components of postoperative pain management strategies.^10,11

This introduction sets the stage for a detailed exploration of the clinical effectiveness of these anesthetic combinations, ensuring that the study’s findings will contribute significantly to the refinement of pain management protocols in spinal surgery, potentially setting new benchmarks for postoperative care.

Study Design and Setting

This prospective, randomized, double-blinded study received ethical clearance from the institutional review board. Informed consent was obtained from all participants prior to their inclusion in the study, which was conducted on patients undergoing lumbar spine surgery under general anesthesia.

Participants
Inclusion Criteria:

• Adults aged 18 to 60 years.
• Classified under the American Society of Anesthesiologists (ASA) physical status Classes I and II.
• Scheduled for lumbar spine surgery under general anesthesia.

Exclusion Criteria:

• Known allergies to study medications.
• History of seizure disorders.
• Presence of severe systemic diseases or diabetes.
• Psychiatric conditions.
• Coagulopathies.
• Regular opioid usage.

Randomization and Blinding

Participants were introduced to the Visual Analogue Scale (VAS) for pain, which ranges from 0 (no pain) to 10 (worst imaginable pain), during the pre-anesthetic evaluation. Preoperative VAS scores were recorded at the pre-anesthetic checkup. Patients were randomized into two groups using computer-generated tables: Group BM (n = 20) and Group BD (n = 20). Study drugs were prepared by an anesthesia resident not involved in the study, and both the surgeon and the anesthetist were blinded to the group assignments.

Intervention
Group BM received an infiltration consisting of 50 mg of bupivacaine with 500 mg of magnesium sulfate, diluted to a total volume of 20 mL with normal saline. Group BD received 50 mg of bupivacaine with 4 mg of dexamethasone, also diluted to 20 mL with normal saline. The infiltration was administered into the paravertebral muscles, 10 mL on each side, using a three-point technique with a 22-gauge needle, limited to a maximum of two levels.

Anesthetic Procedure

Patients were required to fast overnight and were premedicated with 0.5 mg oral alprazolam and 150 mg ranitidine the night before and the morning of surgery. Standard ASA monitoring was employed, and baseline vitals were documented in the operating room. Anesthesia induction was achieved with 2 mg/kg IV propofol and maintained with 66% nitrous oxide in oxygen and 1% isoflurane, along with intermittent doses of vecuronium and paracetamol as required. Muscle relaxation for tracheal intubation was facilitated with 0.1 mg/kg IV vecuronium.

Surgical and Postoperative Procedures

A standard 8–10 cm incision was utilized for lumbar laminectomy. Local infiltration with the study drug occurred 30 minutes before skin closure. Following surgery, neuromuscular blockade reversal was performed using neostigmine (0.05 mg/kg) and glycopyrrolate (0.01 mg/kg). Patients were extubated upon regaining consciousness and responsiveness to commands.

Postoperative Assessment

Postoperatively, patients were monitored in the post-anesthetic care unit where VAS pain scores were assessed hourly until a score of >5 was reached or up to the first 24 hours postoperatively by a third anesthesia resident blinded to the group assignments. The duration of analgesia was measured from the end of surgery until either a VAS score of >5 was noted or the first analgesic request was made. Rescue analgesia with 1 g IV paracetamol was administered as needed, and side effects were documented and reported.

Study Design

This study was designed as a comparative two-group clinical trial aimed at evaluating the effectiveness of bupivacaine plus magnesium sulfate versus bupivacaine plus dexamethasone in postoperative analgesia.

Statistical Analysis

Data were presented as means with 95% confidence intervals. The normality of continuous variables (height, weight, age) was assessed using Kolmogorov-Smirnov and Shapiro-Wilk tests. Categorical data (gender) were expressed in frequency of occurrence.

For continuous data, inter-group comparisons were performed using analysis of variance (ANOVA). Categorical data comparisons were conducted using Pearson Chi-square, continuity correction, likelihood ratio, and Fisher’s exact test. A p-value of less than 0.05 was considered statistically significant.

Demographics and Clinical Outcomes

In both Groups BM and BD, demographic parameters such as age, sex, and duration of surgery were found to be comparable. There were no significant changes in heart rate, blood pressure, and oxygen saturation as per the data presented in Tables 1 to 4. Sedation scores immediately postoperative (at 0 and 5 minutes) were comparable and showed significant differences (P < 0.005, Figure 1).

Postoperative Analgesia

The efficacy of postoperative analgesia was notably higher in the BM group. Rescue analgesia was required by 19 out of 20 patients in Group BD between 7–10 hours post-surgery, whereas in Group BM, rescue analgesia was predominantly needed after 11 hours. Lower VAS scores were observed in Group BM compared to Group BD, indicating better pain management (Tables 6-8).

TABLE 1: PULSE RATE (PR) COMPARISON IN TWO GROUPS

TABLE 2: SYSTOLIC BLOOD PRESSURE (SBP) COMPARISON IN TWO GROUPS

TABLE 4: SPO2 PERCENTAGE COMPARISON IN TWO GROUPS OF COHORTS STUDIED

TABLE 5: FIRST ANALGESIC REQUEST (HOURS)

TABLE 6: VAS COMPARISON IN TWO GROUPS OF COHORTS STUDIED

TABLE 7: VAS FREQUENCY DISTRIBUTION IN TWO GROUPS OF PATIENTS STUDIED (COHORT)

In this randomized, double-blinded study, the efficacy of bupivacaine combined with magnesium sulfate was compared against bupivacaine with dexamethasone for managing postoperative pain following lumbar spine surgeries. The use of bupivacaine, a long-acting local anesthetic, was enhanced by these adjuvants to potentially extend its analgesic effects and improve patient comfort during the critical postoperative period.¹²

The results demonstrated that both adjuvants, when combined with bupivacaine, provided effective analgesia, but there were notable differences in the duration and quality of pain relief. Patients in the BM group (bupivacaine and magnesium sulfate) typically required rescue analgesia later than those in the BD group (bupivacaine and dexamethasone), suggesting a prolonged analgesic effect of the magnesium sulfate combination. This could be attributed to the NMDA receptor antagonism by magnesium sulfate, which may contribute to a more sustained modulation of pain pathways.^13,14

Furthermore, the anti-inflammatory properties of dexamethasone, while effective in reducing immediate postoperative discomfort, did not extend the duration of analgesia as effectively as anticipated. This finding aligns with existing literature that supports the role of glucocorticoids in inflammation control but indicates a potential limitation in pain threshold modulation over extended periods post-surgery.^15,16

The clinical implications of these findings suggest that while both adjuvants are beneficial, the choice of adjuvant may need to be tailored based on the anticipated duration of acute postoperative pain and the specific surgical context. For surgeries anticipated to have a longer duration of acute postoperative pain, magnesium sulfate could be preferable.^17,18,19

Additionally, no significant adverse effects were reported in either group, reinforcing the safety of both adjuvant therapies when used in this context. This is particularly important given the ongoing concerns regarding opioid use and the need for effective non-opioid pain management strategies in postoperative care.

The study underscored the effectiveness of both magnesium sulfate and dexamethasone as adjuvants to bupivacaine for postoperative analgesia in lumbar spine surgery. Magnesium sulfate showed a superior duration of pain control, suggesting its role in extending the analgesic benefits of bupivacaine. These findings advocate for a tailored approach to postoperative pain management, emphasizing the need to match the pharmacological profile of adjuvants with specific patient and surgical requirements to optimize outcomes. Future research should focus on refining adjuvant combinations and concentrations to further enhance postoperative recovery and patient satisfaction.

1. Garcia RM, Cassinelli EH, Messerschmitt PJ, Furey CG, Bohlman HH. A multimodal approach for postoperative pain management after lumbar decompression surgery: A prospective, randomized study. J Spinal Disord Tech. 2013;26:291-297.
2. Patel L, Shah K, Padhiyar V, Patel K, Patel B. Pre-emptive incision infiltration versus post-operative wound infiltration with 0.5% ropivacaine in patients undergoing lumbar laminectomy. Indian J Clin Anaesth. 2015;2:217-221.
3. Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature. 1983;306:686-688.
4. Mirzai H, Tekin I, Alincak H. Perioperative use of corticosteroid and bupivacaine combination in lumbar disc surgery: A randomized controlled trial. Spine (Phila Pa 1976). 2002;27:343-346.
5. Albrecht E, Kirkham KR, Liu SS, Brull R. Peri-operative intravenous administration of magnesium sulphate and postoperative pain: A meta-analysis. Anaesthesia. 2013;68:79-90.
6. Ghaffaripour S, Mahmoudi H, Eghbal H, Rahimi A. The effect of intravenous magnesium sulfate on post-operative analgesia during laminectomy. Cureus. 2016;8
7. Donadi PK, Moningi S, Gopinath R. Comparison of bupivacaine and bupivacaine plus magnesium sulphate infiltration for postoperative analgesia in patients undergoing lumbar laminectomy: A prospective randomised double‑blinded controlled study. J Neuroanaesth Crit Care. 2014;1:183-187.
8. Zhang S, Song M, An W, Wang Z. Effects of different doses of dexamethasone as local anesthetic adjuvant on brachial plexus block: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2021;100
9. Chazapi A, Lepetsos P, Gambopoulou Z, Siafaka I, Argyra E, Vadalouka A. Analgesic effect of the topical use of dexamethasone in ultrasound-guided axillary brachial plexus blockade: A prospective, randomized, double-blind, placebo-controlled study. Cureus. 2021;13
10. Hazarika R, Parua S, Choudhury D, Barooah RK. Comparison of bupivacaine plus magnesium sulfate and ropivacaine plus magnesium sulfate infiltration for postoperative analgesia in patients undergoing lumbar laminectomy: A randomized double-blinded study. Anesth Essays Res. 2017;11:686-691.
11. Boezaart AP, Munro AP, Tighe PJ. Acute pain medicine in anesthesiology. F1000Prime Rep. 2013;5:54.
12. Morrison I, Perini I, Dunham J. Facets and mechanisms of adaptive pain behavior: Predictive regulation and action. Front Hum Neurosci. 2013;7:755.
13. Guilfoyle MR, Mannion RJ, Mitchell P, Thomson S. Epidural fentanyl for postoperative analgesia after lumbar canal decompression: A randomized controlled trial. Spine J. 2012;12:646-651.
14. Kluba T, Hofmann F, Bredanger S, Blumenstock G, Niemeyer T. Efficacy of post-operative analgesia after posterior lumbar instrumented fusion for degenerative disc disease: A prospective randomized comparison of epidural catheter and intravenous administration of analgesics. Orthop Rev (Pavia). 2010;2
15. Rudra A, Chaterjee S, Ray S, Ghosh S. Pain management after spinal surgery. Indian J Pain. 2015;29:9-14.
16. Fisher CG, Belanger L, Gofton EG, Umedaly HS, Noonan VK, Abramson C, et al. Prospective randomized clinical trial comparing patient-controlled intravenous analgesia with patient-controlled epidural analgesia after lumbar spinal fusion. Spine (Phila Pa 1976). 2003;28:739-743.
17. Hernández-Palazón J, Tortosa Serrano JA, Burguillos López S, Molero Molero E. Infiltration of the surgical wound with local anesthetic for postoperative analgesia in patients operated on for lumbar disc herniation: Comparative study of ropivacaine and bupivacaine. Rev Esp Anestesiol Reanim. 2001;48:17-20.
18. Gunduz A, Bilir A, Gulec S. Magnesium added to prilocaine prolongs the duration of axillary plexus block. Reg Anesth Pain Med. 2006;31:233-236.
19. Ong CK, Lirk P, Seymour RA, Jenkins BJ. The efficacy of preemptive analgesia for acute postoperative pain management: A meta-analysis. Anesth Analg. 2005;100:757-773.