Abstract
Background:
Effective pain management following spinal surgery is crucial for preventing complications related to delayed mobilization. Magnesium sulfate (MgSO4) has shown promise as an analgesic agent, influencing neurotransmitter modulation and autonomic nervous system regulation. However, studies evaluating its effectiveness and safety in spinal surgery remain inconsistent, necessitating a comprehensive meta-analysis to assess its role.
Objective:
This study aimed to perform a systematic meta-analysis to compare the safety and efficacy of magnesium sulfate against standard therapeutic options in spinal surgery.
Methods:
The meta-analysis followed PRISMA guidelines. We performed data extraction and analysis using Review Manager version 5.4. The study population included patients undergoing spinal surgery, with the intervention group receiving intravenous magnesium sulfate at varying dosages or in combination with other agents. The comparison group received either a placebo or alternative treatments. Primary outcomes included pain intensity, opioid consumption, and safety parameters.
Results:
Ten randomized controlled trials involving 641 patients were included. Magnesium sulfate administration significantly reduced pain scores at 24 h (MD −0.18, 95% CI: −0.34 to −0.02) and decreased opioid consumption (SMD −0.34, 95% CI: −1.07 to −0.35). Additionally, a significant reduction in muscle relaxant usage was observed (SMD −0.91, 95% CI: −0.66 to −0.10). When compared with dexmedetomidine, magnesium sulfate improved verbal response (MD 1.22, 95% CI: −0.16–2.61) and prolonged extubation time (MD 0.91, 95% CI: −0.98–2.80). No significant differences in hemodynamic parameters (heart rate and blood pressure) were observed between the groups.
Conclusion:
Intravenous magnesium sulfate demonstrated significant benefits in reducing postoperative pain and opioid consumption, while also improving verbal response and orientation. These findings suggest that magnesium sulfate may serve as a valuable adjunct in the perioperative management of spinal surgery patients. Further research is required to confirm these results and establish optimal dosing protocols.
1 Introduction
Chronic low back pain represents a significant burden on healthcare systems worldwide (). The management of this condition requires a stepwise, progressive approach that prioritizes conservative treatments, including physiotherapy and lifestyle modifications. However, in severe and refractory cases, invasive interventions such as epidural steroid injections or surgical procedures may become necessary (). While epidural steroid injections have demonstrated Level I evidence in treating radicular pain associated with disc herniation, concerns persist regarding their safety due to rare but potentially severe neurological complications ().
Within this therapeutic landscape, various interventions for low back pain have been investigated. Ozone therapy, for instance, has shown promise in pain relief, though it remains controversial due to limited long-term evaluation and unclear mechanisms of action (). Extensive research has been conducted on adjuvant medications in spine surgery, particularly focusing on ketamine and gabapentin use in adolescents undergoing spinal fusion for idiopathic scoliosis. These trials primarily evaluated the medications’ effectiveness in reducing postoperative pain and minimizing opioid consumption. Notably, these studies have demonstrated significant reductions in both opioid use and pain intensity during the initial 48 postoperative hours, accompanied by favorable safety profiles and low adverse event rates (; ).
Postoperative pain management remains a critical concern for both clinicians and patients, as delayed mobilization can lead to serious adverse outcomes (). The impact of acute pain has been well-documented in numerous studies. Multiple therapeutic modalities, encompassing both pharmacological and non-pharmacological approaches, have been employed to address postoperative pain, which significantly influences patient prognosis and treatment outcomes ().
Magnesium, an inorganic ion, has diverse therapeutic applications, including the management of asthma exacerbations, hypokalemia, premature labor, myocardial protection following ischemia, postoperative acute pain control, and hemodynamic stabilization during intubation (). Among magnesium preparations, magnesium sulfate has gained particular attention, with its value being evaluated in numerous anesthesia-related investigations (; ). The anti-nociceptive properties of magnesium (Mg) are attributed to its antagonistic effect on N-Methyl-D-aspartate (NMDA) receptors. While preoperative magnesium administration has shown limited impact on postoperative pain, several clinical trials have demonstrated that magnesium infusion during general anesthesia reduces both anesthetic requirements and postoperative analgesic consumption (). However, the effects of magnesium sulfate administration during regional anesthesia remain incompletely characterized.
Current evidence regarding magnesium sulfate use in spinal surgery is both conflicting and incomplete. While some studies have reported favorable outcomes, including improved hemostatic parameters, reduced intraoperative bleeding, and enhanced pain scores and patient satisfaction (; ), others have documented adverse effects such as prolonged emergence time and delayed recovery (). Despite these contradictory findings, no meta-analysis has specifically focused on magnesium sulfate use in spinal surgery. Previous literature reviews have noted “low statistical power” in existing studies, highlighting the need for a comprehensive analysis of available data to determine the effectiveness and safety profile of magnesium sulfate in spinal surgery procedures.
Therefore, this study aimed to conduct a comprehensive meta-analysis to evaluate the efficacy and clinical significance of magnesium sulfate administration in spinal surgery.
2 Materials and methods
2.1 Eligibility criteria
This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study selection process is illustrated in Figure 1 (). Study inclusion criteria were developed using the PICOS framework. The study population comprised adult patients who underwent spinal surgery. The intervention group received intravenous magnesium sulfate (MgSO4) treatment in varying combinations or doses, while the comparison group received either placebo or alternative treatments. Primary outcomes included efficacy metrics (pain management, medication usage, hemodynamic parameters) and safety outcomes determined through complication analysis. Only randomized controlled trials (RCTs) were considered eligible for inclusion.
FIGURE 1
To minimize bias and prevent data duplication, studies with the following characteristics were excluded:
• Duplicate publications
• Non-randomized studies, due to their inherent limitations in establishing causal relationships and controlling for confounding variables
• Review articles, as they represent secondary analyses rather than primary data
• Studies with incomplete or missing data, to ensure result accuracy and consistency
• Studies that did not share variables with at least two other included studies, to enable meaningful data pooling and robust statistical analysis
2.2 Information sources and search strategy
A comprehensive literature search was conducted across multiple databases without language or publication date restrictions. The final search was performed in October 2023, encompassing PubMed, Google Scholar, ScienceDirect, and the Cochrane Library. The search strategy employed the Medical Subject Heading (MeSH) terms “Magnesium” and “spine” (detailed search strategy provided in Supplementary Material 1). Additionally, reference lists of included articles were manually screened to identify additional relevant studies.
Study selection was performed independently by two reviewers with Level V expertise (; ). In cases of disagreement, a third reviewer was consulted to reach consensus. The detailed study selection process is presented in the PRISMA flow diagram (Figure 1).
2.3 Data extraction and data items
Data extraction was conducted independently by two reviewers with Level V expertise, with discrepancies resolved through consultation with a third reviewer (
;
). The following data were extracted from each included study:
• Study characteristics (author, location, study duration).
• Patient demographics (mean age, gender distribution).
• Clinical indicators (etiology, spinal drug dosage).
• Primary outcome measures:
o Pain assessment using Visual Analog Scale (VAS).
o Medication usage (opioids, muscle relaxants, remifentanil).
o Hemodynamic parameters (heart rate [HR], mean arterial pressure [MAP]).
o Recovery indicators (extubation time, verbal command response, orientation time).
2.4 Risk of bias assessment
The risk of bias in included studies was evaluated using the Cochrane Collaboration’s risk of bias tool and analyzed using Review Manager software (
Figure 2). Assessment domains included:
• Random sequence generation.
• Allocation concealment.
• Blinding of participants and personnel.
• Blinding of outcome assessments.
• Incomplete outcome data.
• Selective reporting.
FIGURE 2
2.5 Publication bias
Review Manager was used to assess publication bias through funnel plot analysis. Funnel plots provide a visual method for examining publication bias by plotting study precision (measured by sample size or standard error) against effect sizes. As shown in Figure 3, the asymmetrical distribution suggests the presence of publication bias, potentially due to the exclusion of smaller studies with non-significant results from the analysis. Additional subgroup analyses were performed to account for multiple time points of outcome measurement, enabling more comprehensive data interpretation.
FIGURE 3
2.6 Statistical analysis
Data analysis was performed using Review Manager 5.4 software. For continuous outcomes, mean differences were calculated, while odds ratios were computed for dichotomous outcomes. All results were presented with 95% confidence intervals. Heterogeneity was assessed using I2 and Chi2 tests, with I2 values > 25%, >50%, and >75% indicating low, moderate, and high heterogeneity, respectively. A fixed-effects model was employed in the absence of significant heterogeneity, while a random-effects model was used when heterogeneity was detected.
Data from figures were extracted using Web Plot Digitizer version 4.5. Missing data were handled according to Cochrane Handbook guidelines (). Publication bias was assessed using Review Manager-generated funnel plots, with asymmetrical distribution indicating potential publication bias. Subgroup analyses were conducted to evaluate outcomes at different time points, enabling more detailed data analysis.
3 Results
3.1 Study selection
The systematic literature search initially identified 415 potentially relevant studies. After applying the clinical trial filter, 381 studies were excluded, leaving 34 studies for further evaluation. Following title and abstract screening, 21 studies were excluded based on predefined criteria: they were either study protocols, non-human studies, pharmacokinetic studies, or studies not focused on spinal surgery.
Of the remaining 13 studies that underwent full-text review, three were subsequently excluded due to:
• Non-shared outcome variables
• Duplicate publications
• Non-intravenous magnesium sulfate administration routes
• Significant heterogeneity in inclusion criteria
Manual screening of reference lists from included studies did not yield any additional eligible articles. Therefore, ten randomized controlled trials were ultimately included in the meta-analysis, as illustrated in the PRISMA flow diagram (Figure 1).
3.2 Study characteristics
The primary characteristics of the included studies are summarized in Table 1. The meta-analysis comprised ten studies with a total of 641 participants: 295 in the magnesium sulfate (MS) group, 163 in the placebo group, 103 in the dexamethasone group, and 80 in the dexmedetomidine group. The mean age of participants ranged from 32.2 to 55.9 years, with 301 participants (46.9%) being female. Table 1 presents the detailed MS dosage regimens and surgical indications for each study. The risk of bias assessment for the included studies is presented in Figure 3.
TABLE 1
| Study | Region | Dose MgSo4 | Surgery site | No. of patients treatment/Placebo | No. of females (MS/PL) | Age | Period |
|---|---|---|---|---|---|---|---|
| Turkey | 30 mg/kg 1 over a 15-min period before induction of anesthesia and 10 mg/kg 1 h | Spine surgery | 60 (30/30) | 7/7 | 42.3/44.9 | NR | |
| Turkey | 50 mg/kg in 100 mL saline by slow infusion over 10 min, followed by a continuous infusion of 20 mg/kg/h | Single-level microscopic lumbar discectomy | 40 (20/20) | 10/11 | 48/49 | NR | |
| India | 15 mL of 0.75% ropivacaine +500 mg equivalent to 1 mL + 4.0 mL normal saline. The total volume of the solution infiltrated was 20 mL in both groups | Single-level lumbar laminectomy | 60 (30/30) | 8/5 | 35.2/38.2 | NR | |
| Levaux et al. (2003) | Belgium | 50 mg/kg in 250 mL of normal saline over 30 min immediately before induction of anesthesia | Lumbar arthrodesis | 24 (12/12) | 8/5 | 55/46 | NR |
| Oguzhan et al. (2008) | Turkey | 30 mg/kg (over 10 min) starting immediately after induction of anesthesia and completed before intubation; the infusion was then continued at 10 mg/kg/h throughout surgery | Lumbar disc surgery | 50 (25/25) | 12/11 | 44/42 | 2005 to 2006 |
| Korea | 30 mg/kg in a total of 100 mL normal saline was given for 10 min before the induction of anesthesia, followed by continuous infusion of at 10 mg/kg/h until the end of operation | Lumbar spine surgery | 146 (73/73) | 32/31 | 51/51 | 2013 to 2014 | |
| India | Loading dose 50 mg/kg before induction over a period of 15 min and maintenance 15 mg/kg/h throughout the surgery | Elective spine surgery | 90 (45/45) | 19/20 | 48.3/46.6 | NR | |
| Greece | 20 mg/kg diluted in isotonic saline to a volume of 100 mL was infused as an intravenous (i.v.) bolus dose over 15 min before anesthesia induction and thereafter 20 mg/kg/h was continuously infused until surgery completion | Lumbar laminectomy | 71 (35/36) | 22/21 | 55.9/49 | 2020 | |
| Korea | magnesium sulphate 50 mg/kg for 15 min and then 15 mg/kg per hour by continuous i.v | spinal surgery | 40 (20/20) | 11/7 | 47/49.9 | NR | |
| Dabbagh et al. (2009) | Iran | magnesium sulphate dose of 8 mg/kg/h of body weight | Lower limb orthopedic surgery | 60 (30/30) | 21/24 | 33.7/35.1 | NR |
The main characteristics of included studies.
Notes: NR: no data reported.
A comparative analysis of different treatment approaches and anesthesia techniques in spinal surgery pain management is provided in Table 2. This analysis includes various interventions such as esketamine combined with pregabalin, dexmedetomidine, patient-controlled analgesia (PCA), and acupuncture, highlighting their respective outcomes and clinical significance in spinal surgery patients.
TABLE 2
| Author, year | Patient population | Treatment | Operation type | Conclusion |
|---|---|---|---|---|
| Zhou, (2024) | Spinal cord surgery patients between the ages of 18 and 65 | Patients were randomized to receive esketamine (injection dose 0.5 mg· kg-1, infusion dose 0.12 mg· kg-1 · h-1, 48 h after surgery) combined with oral pregabalin (75–150 mg/day, beginning 2 h before surgery and ending 2 weeks after surgery) or equivalent saline and placebo capsules | Moderate-to-severe acute postsurgical pain | Esketamine combined with pregabalin is effective in alleviating APSP after spinal surgery, but analgesic strategies may increase the risk of mild dissociation symptoms |
| 40 patients undergoing posterior lumbar interbody fusion (PLIF) under general anesthesia | A total of 40 patients underwent posterior lumbar interbody fusion (PLIF) under general anesthesia. Anesthesia was maintained at 3–12 mg/kg/h with propofol, 0.01–0.2 μg/kg/min in remifentanil group and 0.01–0.02 μg/kg/min in dexmedetomidine group, and the bispectral index was maintained between 40 and 60 | Total intravenous anesthesia (TIVA) | Dexmedetomidine showed superior efficacy in pain relief and pain management 48 h after PLIF. | |
| Records of successive patients who underwent surgical treatment for degenerative lumbar disease in our hospital from 2013 to 2014 | Patients were grouped according to pain control methods, including routine analgesia, patient-controlled analgesia (PCA), and acupuncture. The routine analgesia group took acetaminophen/NSaids and piperidine orally as needed for immediate pain control. The PCA group received a base dose of morphine and a subsequent user-required dose. In the acupuncture group, acupuncture was performed every other day | The procedure included open laminectomy, discectomy, and posterolateral fusion with transpedicle screw internal fixation | For adjunctive pain control after surgery for degenerative lumbar disease, acupuncture may be as effective as traditional analgesia and PCA | |
| Rahimzadeh, (2018) | 60 patients aged 15–65 years who were undergoing posterior spinal fusion | A double-blind randomized clinical trial was conducted in 60 patients aged 15–65 years who were to undergo posterior spinal fusion by random sampling. Intraoperative anesthesia was induced and 1% isoflurane was used in both groups. One group was injected with remifentanil by pumping. The experimental group was given dexmedetomidine | Spinal fusion patients | Dexmedetomidine reduced postoperative pain scores and intraoperative bleeding in patients undergoing spinal surgery. The hemodynamic effect of dexmedetomidine group was significantly improved |
| Umakoshi, (2021) | A total of 156 non-PD patients treated for spinal degenerative diseases and PD patients after spinal surgery from 2013 to 2017 | The Hoehn and Yahr scores of D were 8 cases in stage 1, 2 cases in stage 2, 8 cases in stage 3, 10 cases in stage 4, and 0 cases in stage 5. The median daily equivalent dose of levodopa before surgery was 410 mg. Thirteen patients (46%) received subthalamic nucleus (STN) DBS. | Parkinson’s disease | Postoperative pain and functional improvement in PD patients lasted for 2 years, and the complication rate was higher than that in non-PD patients. PD patients with STN DBS maintained good lumbar lordosis 2 years after spinal surgery. STN DBS significantly maintained spinal alignment 2 years after surgery, with pain and improved function |
| Lee, (2018) | Patients were recruited from a medical center in central Taiwan. Ninety patients participated in the study | Patients who underwent lumbar surgery (n = 86) were randomly assigned to the intervention group (educational intervention; n = 43) or control group (n = 43); Four patients voluntarily withdrew after surgery (1 case in the intervention group; Control group (3 cases) | spinal surgery | Preoperative educational interventions are effective in informing patients undergoing spinal surgery of reduced postoperative pain, anxiety, and fear |
A comparative of different treatments and anesthesia TechniquesSpinal in surgery pain management and outcomes.
The global VAS (MD 0.56, 95% CI −1.47 to 0.36; participants = 1,232; studies = 15; I2 = 99%) showed no discernible differences (Figure 4). Comparably, at 6 h (MD −0.38, 95% CI −2.59 to 1.83; participants = 536; studies = 6; I2 = 99%) and 12 h (MD −1.40, 95% CI −2.64 to 0.34; participants = 160; studies = 3; I2 = 96%), no significant differences were discovered. After a full day, however, the magnesium group displayed noticeably less discomfort than the control group (MD−0.18, 95% CI−0.34, −0.02; participants, 536; studies, 6; I2 = 0%). When comparing MS with a placebo, MS showed a much higher global VAS reduction. There were no discernible changes between MS and dexmedetomidine. Likewise, no noteworthy distinctions were noted when contrasting MS with dexamethasone. The subgroup test is 1.20 and the overall effect test is 2.16.
FIGURE 4
3.2.1 Drug consumption
In relation to opioid consumption, no significant differences were observed at 6 h (SMD−0.35, 95%CI−0.82 to 0.13; participants = 244; studies = 3; I2 = 63%) or 24 h (SMD−0.36, 95% CI−1.07 to 0.35; participants = 243; studies = 3; I2 = 83%) (Figure 5). When magnesium was compared to a placebo, it was found to significantly reduce opioid consumption (SMD−0.66, 95%CI −0.95 to −0.38; participants = 196; studies = 6; I2 = 0%), both at 6 and 24 h (SMD−0.71, 95% CI −1.12 to −0.30; participants = 98; studies = 3; I2 = 0%). In terms of overall or at six or 24 h, there were no significant differences between MS and dexamethasone (SMD 0.10, 95% CI−0.13 to 0.33; participants = 292; studies = 6; I2 = 0%). Test results for the subgroup are 1.82 and the overall impact are 1.00.
FIGURE 5
The MS group’s use of muscle relaxants was significantly lower among participants (252) and studies (3) (SMD −0.91, 95% CI−1.93 to −0.10; I2 = 92%) (Figure 6) MS had a significantly decreased consumption of muscle relaxants when compared to a placebo. The total impact test is 1.77 and the chi2 value is 0.73.
FIGURE 6
Vasoactive agent use did not differ significantly (OR 1.87, 95% CI 1.01 to 3.46; participants = 315; studies = 4; I2 = 0%) from (Figure 7). Not at all in contrast to a placebo. The chi2 value is 1.72 and the overall impact test is 1.99.
FIGURE 7
3.2.2 Hemodynamics
Regarding global heart rate (MD 2.37, 95% CI −0.66 to 5.10; participants = 797; studies = 17; I2 = 24%), there were no significant changes between the groups or in any of the follow-up time-based subgroups (Figure 8). The MS group displayed a considerably greater heart rate in comparison to the placebo. When MS was compared with clonidine, no discernible differences were found. Test results for subgroup difference are 0.40 and total effect are 0.55.
FIGURE 8
Figure 9 indicates that there were no significant variations in mean arterial pressure (MAP) across the groups (MD 1.81, 95% CI−2.55 to 6.17; 950 participants, 20 studies, and 57% I2). Notably, there were no variations when compared to the placebo group. MS displayed a considerably decreased MAP in contrast to clonidine. Regarding dexmedetomidine, there were no notable variations. The subgroup test is 0.55 while the overall effect test is 0.45.
FIGURE 9
3.2.3 Extubating time, response to verbal commands and orientation time
There was no statistically significant difference in extubating time between the groups (Figure 10; participants = 364, studies = 5, I2 = 94%; MD 0.91, 95% CI -0.98–2.80). With respect to the placebo group, there were no appreciable variations. The MS group had a considerably longer extubation time in comparison to dexmedetomidine. The overall effect test result is 0.94, and chi2 is 71.91.
FIGURE 10
Figure 11 shows that the MS group’s responsiveness to verbal orders was considerably higher (MD 1.22, 95% CI -0.166 to 2.61; participants = 291; studies = 4; I2 = 76%). With respect to the placebo group, there were no appreciable variations. In contrast to the clonidine group, the MS group displayed a noticeably slower response time to spoken instructions. Chi2 is 12.27 and the test for the total effect is 1.73.
FIGURE 11
Additionally, the orientation time was substantially longer in the MS group compared to the placebo group (MD: 2.07, 95% CI 0.82 to 3.32; participants = 146; studies = 3; I2 = 59%) (Figure 12). The test effect was 3.25 overall, and the chi2 was 4.91.
FIGURE 12
3.2.4 Publication bias
Visual inspection of funnel plots revealed significant publication bias across most variables, as evidenced by notable asymmetry in the distribution of studies. Detailed analysis of these asymmetries and their implications is presented in the supplementary materials.
The therapeutic benefits of magnesium in postoperative pain management likely stem from its multifaceted neuroprotective and anti-inflammatory mechanisms (). Through the promotion of neuroplasticity, magnesium provides protection against neuronal deterioration and postoperative cognitive dysfunction (). Its antioxidant properties are demonstrated through the neutralization of reactive oxygen species (ROS), specifically via hydrogen peroxide (H2O2) elimination and hydrogen (H2) liberation, contributing significantly to its anti-inflammatory effects in treating intervertebral disc degeneration (IVDD) (; ).
The neuroprotective profile of magnesium extends to its modulation of S100B protein levels, a recognized biomarker of oxidative stress and amyloid precursor (). Clinical investigations have revealed that magnesium’s efficacy in managing postoperative sore throat is comparable to corticosteroids, potentially contributing to enhanced patient satisfaction. This finding is particularly noteworthy given that patient-reported outcome measures (PROMs) were primarily limited to Visual Analog Scale (VAS) assessments (). The comparison with corticosteroids merits special attention, considering their adverse metabolic effects, particularly on glucose homeostasis. The therapeutic benefit appears to be mediated through magnesium’s anti-inflammatory properties, resulting in reduced postoperative nausea, vomiting, and subsequent throat discomfort (; ).
A significant limitation across studies was the absence of minimum clinically important difference (MCID) assessments, highlighting a crucial area for future investigation. The marked reduction in opioid consumption observed with magnesium administration, compared to placebo, can be mechanistically explained by its non-competitive N-methyl-D-aspartate (NMDA) receptor antagonism. This mechanism results in decreased glutamate release and inhibition of excessive calcium influx into neurons, thereby providing neuroprotection and maintaining cellular integrity (). Similar opioid-sparing effects have been documented with other NMDA receptor antagonists, including gabapentin and ketamine ().
The neuroprotective properties of magnesium sulfate have broader clinical applications, as evidenced by its recommended use in reducing cerebral palsy incidence among preterm infants, particularly those at risk of delivery before 32 weeks gestation (). Through dual mechanisms of neuronal process stabilization and vasodilation, intracerebral magnesium sulfate reduces the incidence of cerebral vasospasm and delayed cerebral ischemia. Complementary intravenous hydrogen therapy may enhance these effects through additional antioxidant benefits, potentially improving clinical outcomes and reducing cerebral oxidative stress ().
3.2.5 Hemodynamic and cardiovascular effects
Our analysis revealed lower mean arterial pressure in the magnesium group compared to the corticosteroid group, attributable to magnesium’s vasodilatory properties. Magnesium exerts its hypotensive effect through multiple mechanisms: direct relaxation of blood vessels, calcium channel antagonism, and competition with sodium in vascular smooth muscle cells. Furthermore, magnesium enhances endothelial function and vascular wall integrity, promoting vasodilation and reducing inflammation (). The observed increase in heart rate in our meta-analysis likely represents a compensatory response to this vasodilation, while the higher mean arterial pressure in the corticosteroid group can be attributed to adrenergic system activation.
The hypotensive properties of magnesium contribute to reduced perioperative bleeding (). Additionally, magnesium modulates sympathetic nervous system activity through catecholamine blockade (). While the magnesium group demonstrated prolonged activated partial thromboplastin time, other coagulation parameters remained comparable between groups ().
3.2.6 Neuromuscular effects and safety considerations
Magnesium’s ability to reduce muscle relaxant requirements is attributed to its inhibition of acetylcholine receptor responses in muscle cells. This synergistic effect potentially allows for dose reduction of muscle relaxants during surgical procedures. However, careful dose titration of both vecuronium and magnesium sulfate is essential to prevent adverse effects and excessive muscle relaxation ().
3.2.7 Risk of hypermagnesemia
Careful monitoring of magnesium levels is crucial, as concentrations exceeding 4–5 mmol/L (9.7–12.2 mg/dL) are considered hazardous. Hypermagnesemia can manifest as weakness, nausea, dizziness, and confusion, with increased mortality risk in hospitalized patients. The prevalence ranges from 3.0% to 5.7%–9.3% in the general population, with higher rates in hospital settings. Patients with renal insufficiency require particularly vigilant monitoring and management to prevent serious complications ().
3.2.8 Recovery period considerations
The prolonged recovery period observed in the magnesium group, characterized by delayed orientation time and verbal response, likely results from the combination of its hypotensive and muscle-relaxant effects. The vasodilatory properties may lead to reduced cerebral perfusion and oxygenation, contributing to extended recovery times and temporary cognitive effects. The muscle-relaxant properties may further impair patient responses during the recovery phase, affecting both verbal communication and orientation capabilities.
3.2.9 Comparative analysis with dexmedetomidine
Dexmedetomidine served as a key comparator in our meta-analysis, providing important insights into alternative therapeutic approaches. As an α2-adrenoceptor agonist, dexmedetomidine demonstrates significant efficacy in reducing surgical stress responses. Our analysis revealed that dexmedetomidine was more effective than magnesium in reducing both fentanyl and propofol consumption. Srivastav et al.'s findings demonstrated superior hemodynamic stability with dexmedetomidine compared to other interventions (). This enhanced hemodynamic profile and greater efficacy in reducing opioid and propofol consumption can be attributed to dexmedetomidine’s high affinity and selectivity for α2-adrenergic receptors. However, these benefits are accompanied by an increased risk of bradycardia and hypotension compared to magnesium therapy ().
3.2.10 Pain management and recovery characteristics
While Kumar’s study reported superior pain control with dexmedetomidine compared to magnesium plus ropivacaine combination, our meta-analysis found no significant differences in pain outcomes between the interventions. Notably, we observed increased muscle relaxant consumption in the dexmedetomidine group. In comparison with placebo, dexmedetomidine demonstrated advantages in orientation time and verbal response parameters. The prolongation of local anesthetic effects observed with dexmedetomidine can be attributed to its vasoconstrictive properties ().
3.2.11 Safety profile and administration considerations
Recent meta-analyses have highlighted specific safety concerns with dexmedetomidine administration during spinal surgery. The risk of bradycardia and intraoperative hypotension is particularly pronounced when administered as a loading dose in combination with total intravenous anesthesia (). These risks were notably elevated in patients receiving inhalation anesthesia. While the inhalation anesthesia subgroup demonstrated reduced blood loss, this effect was not observed consistently across all administration methods ().
3.2.12 Multimodal applications and synergistic effects
Magnesium demonstrates significant potential for synergistic effects when combined with other analgesic modalities. The modest effects observed in comparisons between magnesium sulfate and corticosteroids may be attributed to limited sample sizes and short follow-up periods (typically 24 h). Evidence suggests enhanced patient outcomes when magnesium is combined with various analgesic interventions, including opioids, local anesthetics, and regional anesthesia techniques (). This multimodal approach may provide more comprehensive pain management strategies, though longer-term monitoring beyond the immediate postoperative phase is needed to fully evaluate these benefits.
3.2.13 Administration protocols and dosing strategies
Considerable variation exists in magnesium administration protocols (
). Our meta-analysis evaluated various approaches, including:
• Loading doses: 30–50 mg/kg in saline, administered over 10–30 min pre-anesthesia.
• Maintenance infusions: 10–20 mg/kg/h throughout surgery.
• Alternative approaches: One study evaluated ropivacaine infiltration with 500 mg magnesium supplementation.
While visual analysis of forest plots did not reveal clear associations between administration protocols and outcomes, this observation requires cautious interpretation given the lack of formal statistical analysis.
3.2.14 Broader clinical applications
Magnesium’s therapeutic benefits extend beyond spinal surgery. Evidence demonstrates its efficacy in.
• Reducing postoperative atrial fibrillation in cardiac surgery ().
• Decreasing ventricular arrhythmias without additional adverse effects.
• Improving postoperative pain control in arthroscopic procedures when administered intra-articularly.
• Providing cartilage and chondrocyte protection, as supported by experimental studies ().
Meta-analyses have documented significant reductions in:
• 24-h morphine consumption.
• Time to first analgesic requirement.
• Postoperative shivering without increasing adverse effects such as bradycardia, nausea, or vomiting ().
3.2.15 Surgical outcome analysis
Our study expanded upon previous meta-analyses by incorporating additional outcome measures, including remifentanil and muscle relaxant consumption. Key findings include.
• Peak pain reduction occurred at varying timepoints (6–12 h) across studies (; ).
• Tsaousi et al. uniquely reported decreased extubation time with corresponding reductions in opioid and remifentanil use ().
• Variable outcomes in specific surgical subgroups:
o Microscopic surgery (): Limited comparable outcomes.
o Lumbar disc replacement: Significant improvements in pain control and reduced muscle relaxant requirements ().
o Broader surgical categories (“lumbar arthrodesis,” “spine surgery”): Limited comparative analysis due to heterogeneity ().
Unlike previous meta-analyses focusing on total anesthesia duration, our study specifically examined orientation and verbal response times, though findings aligned with established observations regarding prolonged anesthetic effects.
4 Limitations
There are several restrictions on this study. The restricted number of included studies hindered the ability to do sensitivity and consistent subgroup analysis, as well as to assess the impact of varying doses and surgical indications. To give more detailed advice, future research should describe findings according to the precise kind of surgery that was done. Additionally, rather than using formal procedures, publication bias was evaluated visually, and in several instances, there were just a few publications available for the control groups. Even though the established Cochrane guidelines were adhered to, challenges pertaining to missing data were also observed. Furthermore, several intriguing factors, including improved hemostatic parameters, decreased intraoperative bleeding, and patient satisfaction, were only reported in one trial and could not be compared via meta-analysis. Data on these characteristics should be used in future research. These restrictions should be considered when interpreting the findings, and they highlight the need for more study to address these restrictions in order to gain a more thorough understanding of the application of magnesium in the treatment of postoperative pain.
5 Conclusion
In conclusion, our meta-analysis showed that magnesium sulphate delivery following spinal surgery significantly reduced pain at 24 h and minimized the use of opioids and muscle relaxants when compared to placebo and other analgesics. Magnesium sulphate also extended orientation and reactions to spoken instructions. The groups’ heart rates and blood pressure did not differ significantly from one another. Without causing greater side effects, this multimodal strategy using magnesium sulphate seemed to reduce postoperative pain more well. These results imply that magnesium sulphate may improve recovery regimens optimised after spine surgery and solve current problems associated with opioid use. It is yet unknown how clinical improvements will translate to patient outcomes and what effect they will have on hospital stays, patient satisfaction, and care quality.
Statements
Data availability statement
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
Author contributions
ZJ: Writing – original draft, Conceptualization, Writing – review and editing, Formal Analysis, Supervision. JZ: Writing – original draft, Investigation, Conceptualization, Writing – review and editing.
Funding
The author(s) declare that no financial support was received for the research and/or publication of this article.
Acknowledgments
Thanks to all those who helped with the study but were not listed as co-authors due to insufficient contributions.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declare that no Generative AI was used in the creation of this manuscript.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2025.1624119/full#supplementary-material
References
1
Aal-HamadA. H.Al-AlawiA. M.KashoubM. S.FalhammarH. (2023). Hypermagnesemia in clinical practice. Medicina59 (7), 1190. 10.3390/medicina59071190
2
AltanT.TurgutN.YildizF.BalciN.OzyurekZ.TurhanE. (2005). Effects of magnesium sulphate and clonidine on propofol consumption, haemodynamics and postoperative recovery. British Journal of Anaesthesia, 94 (4), 438–441. 10.1093/bja/aei070
3
BasJ. L.BasP.BonillaF.MariscalG.PérezS.Bovea-MarcoM.et al (2023). Efficacy of perioperative gabapentin use in patients with idiopathic scoliosis undergoing fusion surgery: a systematic review and meta-analysis. Eur. Spine J.32 (7), 2521–2532. 10.1007/s00586-023-07764-8
4
BuvanendranA.McCarthyR. J.KroinJ. S.LeongW.PerryP.TumanK. J. (2002). Intrathecal magnesium prolongs fentanyl analgesia: a prospective, randomized, controlled trial. Anesth. and Analgesia95 (3), 661–666. 10.1097/00000539-200209000-00031
5
ChandlerJ.CumpstonM.LiT.PageM. J.WelchV. (2019). Cochrane handbook for systematic reviews of interventions. Hoboken: Wiley.
6
ChenL.YuL.FanY.MaoJ. (2022). A retrospective comparison of analgesic efficacy between acupuncture, patient-controlled analgesia, and conventional analgesia for postoperative pain management in spinal fusion surgery. Pain Research and Management, 2022, 8494206. 10.1155/2022/8494206
7
DabbaghA.ElyasiH.RazaviS. S.FathiM.RajaeiS. (2009). Intravenous magnesium sulfate for post-operative pain in patients undergoing lower limb orthopedic surgery. Acta Anaesthesiologica Scandinavica, 53 (8), 1088–1091. 10.1111/j.1399-6576.2009.02025.x
8
de AndradeR. R.de Oliveira-NetoO. B.BarbosaL. T.SantosI. O.de Sousa-RodriguesC. F.BarbosaF. T. (2019). Efetividade da ozonioterapia comparada a outras terapias para dor lombar: revisão sistemática com metanálise de ensaios clínicos randomizados. Rev. Bras. Anestesiol.69, 493–501. 10.1016/j.bjan.2019.06.007
9
FairleyJ. L.ZhangL.GlassfordN. J.BellomoR. (2017). Magnesium status and magnesium therapy in cardiac surgery: a systematic review and meta-analysis focusing on arrhythmia prevention. J. Crit. care42, 69–77. 10.1016/j.jcrc.2017.05.038
10
FathyW.HusseinM.IbrahimR. E.Abdel-AzizM. M.AdelS.SolimanS. H.et al (2022). Comparative effect of transforaminal injection of Magnesium sulphate versus Ozone on oxidative stress biomarkers in lumbar disc related radicular pain. BMC Anesthesiol.22 (1), 254. 10.1186/s12871-022-01789-0
11
FerasatkishR.DabbaghA.AlaviM.MollasadeghiG.HydarpurE.MoghadamA.et al (2008). Effect of magnesium sulfate on extubation time and acute pain in coronary artery bypass surgery. Acta Anaesthesiol. Scand.52 (10), 1348–1352. 10.1111/j.1399-6576.2008.01783.x
12
GöralN.ErgilJ.AlptekinA.ÖzkanD.GürerB.DolgunH.et al (2011). Effect of magnesium sulphate on bleeding during lumbar discectomy. Anaesthesia66 (12), 1140–1145. 10.1111/j.1365-2044.2011.06898.x
13
GuyattG. H.ThorlundK.OxmanA. D.WalterS. D.PatrickD.FurukawaT. A.et al (2013). GRADE guidelines: 13. Preparing summary of findings tables and evidence profiles—continuous outcomes. J. Clin. Epidemiol.66 (2), 173–183. 10.1016/j.jclinepi.2012.08.001
14
HassanW. F.TawfikM. H.NabilT. M.Abd ElkareemR. M. (2020). Could intraoperative magnesium sulphate protect against postoperative cognitive dysfunction?Minerva Anestesiol.86 (8), 808–815. 10.23736/S0375-9393.20.14012-4
15
HelmS.HarmonP. C.NoeC.CalodneyA. K.Abd-ElsayedA.KnezevicN. N.et al (2021). Transforaminal epidural steroid injections: a systematic review and meta-analysis of efficacy and safety. Pain Physician24 (S1), S209–S232.
16
HoustonM. (2011). The role of magnesium in hypertension and cardiovascular disease. J. Clin. Hypertens.13 (11), 843–847. 10.1111/j.1751-7176.2011.00538.x
17
HwangJ. Y.NaH. S.JeonY. T.RoY. J.KimC. S.DoS. H. (2010). I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia. British Journal of Anaesthesia, 104 (1), 89–93. 10.1093/bja/aep334
18
HwangS. H.ParkI. K.KangD. H.ParkH. J.LeeY. J. (2015). Dexmedetomidine versus remifentanil in postoperative pain control after spinal surgery: a randomized controlled trial. Medicine, 94 (29), e1161. 10.1097/MD.0000000000001161
19
JamesM. F.BeerR. E.EsserJ. D. (1989). Intravenous magnesium sulfate inhibits catecholamine release associated with tracheal intubation. Anesth. and Analgesia68 (6), 772–776. 10.1213/00000539-198906000-00015
20
JamesonR. A.BernsteinH. B. (2019). Magnesium sulfate and novel therapies to promote neuroprotection. Clin. perinatology46 (2), 187–201. 10.1016/j.clp.2019.02.008
21
KetenciA.ZureM. (2021). Pharmacological and non-pharmacological treatment approaches to chronic lumbar back pain. Turkish J. Phys. Med. rehabilitation67 (1), 1–10. 10.5606/tftrd.2021.8216
22
KumarM.SinghR. B.VikalJ. P.YadavJ. B. S.SinghD. (2023). Comparison of ropivacaine plus dexmedetomidine and ropivacaine plus magnesium sulfate infiltration for postoperative analgesia in patients undergoing lumbar spine surgeries. Cureus15 (3), e36295. 10.7759/cureus.36295
23
LeeT. L.ChangP. C.HuangY. T.ChenY. C.WangJ. J. (2018). Effects of preoperative pain education on postoperative pain control and anxiety in patients undergoing spinal surgery: A randomized controlled trial. Asian Spine Journal, 12 (1), 65–74. 10.4184/asj.2018.12.1.65
24
LevauxC.BonhommeV.DewandreP. Y.BrichantJ. F.HansP. (2003). Effect of intra-operative magnesium sulphate on pain relief and patient comfort after major lumbar orthopaedic surgery. Anaesthesia, 58 (2), 131–135. 10.1046/j.1365-2044.2003.02999.x
25
LuK.-z.ShenH.ChenY.LiM.-g.TianG.-p.ChenJ. (2013). Ondansetron does not attenuate the analgesic efficacy of nefopam. Int. J. Med. Sci.10 (12), 1790–1794. 10.7150/ijms.5386
26
LysakowskiC.DumontL.CzarnetzkiC.TramèrM. R. (2007). Magnesium as an adjuvant to postoperative analgesia: a systematic review of randomized trials. Anesth. and Analgesia104 (6), 1532–1539. 10.1213/01.ane.0000261250.59984.cd
27
MariscalG.MoralesJ.PérezS.Rubio-BelmarP. A.Bovea-MarcoM.BasJ. L.et al (2022). Meta-analysis of the efficacy of ketamine in postoperative pain control in adolescent idiopathic scoliosis patients undergoing spinal fusion. Eur. Spine J.31 (12), 3492–3499. 10.1007/s00586-022-07422-5
28
MentesO.HarlakA.YigitT.BalkanA.BalkanM.CosarA.et al (2008). Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy. Acta Anaesthesiol. Scand.52 (10), 1353–1359. 10.1111/j.1399-6576.2008.01816.x
29
MoriT.KoyamaN.ArendashG. W.Horikoshi‐SakurabaY.TanJ.TownT. (2010). Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease. Glia58 (3), 300–314. 10.1002/glia.20924
30
MorrisonA.HunterJ.HalpernS.BanerjeeA. (2013). Effect of intrathecal magnesium in the presence or absence of local anaesthetic with and without lipophilic opioids: a systematic review and meta-analysis. Br. J. Anaesth.110 (5), 702–712. 10.1093/bja/aet064
31
NaftalovichR.SingalA.IskanderA. J. (2022). Enhanced Recovery after Surgery (ERAS) protocols for spine surgery–review of literature. Anaesthesiol. Intensive Ther.54 (1), 71–79. 10.5114/ait.2022.113961
32
NewcomerJ. W.KrystalJ. H. (2001). NMDA receptor regulation of memory and behavior in humans. Hippocampus11 (5), 529–542. 10.1002/hipo.1069
33
NgK. T.YapJ. L.IzhamI. N.TeohW. Y.KwokP. E.KohW. J. (2020). The effect of intravenous magnesium on postoperative morphine consumption in noncardiac surgery: a systematic review and meta-analysis with trial sequential analysis. Eur. J. Anaesthesiology| EJA37 (3), 212–223. 10.1097/EJA.0000000000001164
34
OguzhanN.GundayI.TuranA. (2008). Effect of magnesium sulfate infusion on sevoflurane consumption, hemodynamics, and perioperative opioid consumption in lumbar disc surgery. Journal of Opioid Management, 4 (2), 105–110. 10.5055/jom.2008.0015
35
ParkJ. H.ShimJ.-K.SongJ.-W.JangJ.KimJ. H.KwakY.-L. (2015). A randomized, double-blind, non-inferiority trial of magnesium sulphate versus dexamethasone for prevention of postoperative sore throat after lumbar spinal surgery in the prone position. Int. J. Med. Sci.12 (10), 797–804. 10.7150/ijms.12831
36
RahimzadehP.FaizS. H. R.ImaniF.DerakhshanP.AmniatiS. (2018). Comparative addition of dexmedetomidine and fentanyl to intrathecal bupivacaine in orthopedic procedure in lower limbs. BMC Anesthesiol.18 (1), 62. 10.1186/s12871-018-0531-7
37
RayssiguierY.LibakoP.NowackiW.RockE. (2010). Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation. Magnesium Res.23 (2), 73–80. 10.1684/mrh.2010.0208
38
ShettyG. M.JainS.ThakurH.KhannaK. (2022). Prevalence of low back pain in India: a systematic review and meta-analysis. Work73 (2), 429–452. 10.3233/WOR-205300
39
SrivastavaV. K.MishraA.AgrawalS.KumarS.SharmaS.KumarR. (2016). Comparative evaluation of dexmedetomidine and magnesium sulphate on propofol consumption, haemodynamics and postoperative recovery in spine surgery: a prospective, randomized, placebo controlled, double-blind study. Adv. Pharm. Bull.6 (1), 75–81. 10.15171/apb.2016.012
40
TakeuchiS.KumagaiK.ToyookaT.OtaniN.WadaK.MoriK. (2021). Intravenous hydrogen therapy with intracisternal magnesium sulfate infusion in severe aneurysmal subarachnoid hemorrhage. Stroke52 (1), 20–27. 10.1161/STROKEAHA.120.031260
41
TangJ. B. (2009). Re: levels of experience of surgeons in clinical studies. J. Hand Surg. Eur. Volume34 (1), 137–138. 10.1177/17531934097321
42
TsaousiG.NikopoulouA.PezikoglouI.BirbaV.GrosomanidisV. (2020). Implementation of magnesium sulphate as an adjunct to multimodal analgesic approach for perioperative pain control in lumbar laminectomy surgery: a randomized placebo-controlled clinical trial. Clin. Neurology Neurosurg.197, 106091. 10.1016/j.clineuro.2020.106091
43
UmakoshiN.ShimizuT.MiyamotoW.KinoshitaM.TakaoM.MatsushitaT.et al (2021). Spinal surgery in patients with Parkinson’s disease: Experiences with the challenges and outcomes. European Spine Journal, 30 (2), 452–461. 10.1007/s00586-020-06656-5
44
ÜnlügençH.GündüzM.ÖzalevliM.AkmanH. (2002). A comparative study on the analgesic effect of tramadol, tramadol plus magnesium, and tramadol plus ketamine for postoperative pain management after major abdominal surgery. Acta Anaesthesiol. Scand.46 (8), 1025–1030. 10.1034/j.1399-6576.2002.460817.x
45
WangM.CheJ.-X.ChenL.SongT.-T.QuJ.-T. (2024). Effect of dexmedetomidine on intraoperative hemodynamics and blood loss in patients undergoing spine surgery: a systematic review and meta-analysis. Chin. Med. Sci. J.39 (1), 54–68. 10.24920/004294
46
YoshitomiT.KohjitaniA.MaedaS.HiguchiH.ShimadaM.MiyawakiT. (2008). Dexmedetomidine enhances the local anesthetic action of lidocaine via an α-2A adrenoceptor. Anesth. and Analgesia107 (1), 96–101. 10.1213/ane.0b013e318176be73
47
ZengC.LiY.-s.WeiJ.XieD.-x.XieX.LiL.-j.et al (2016). Analgesic effect and safety of single-dose intra-articular magnesium after arthroscopic surgery: a systematic review and meta-analysis. Sci. Rep.6 (1), 38024. 10.1038/srep38024
48
ZhangT.WangY.LiR.XinJ.ZhengZ.ZhangX.et al (2023). ROS-responsive magnesium-containing microspheres for antioxidative treatment of intervertebral disc degeneration. Acta Biomater.158, 475–492. 10.1016/j.actbio.2023.01.020
49
ZhouY.YangJ.WangB.WangP.WangZ.YangY.et al (2024). Esketamine combined with pregabalin for acute postsurgical pain after spinal surgery: a randomized controlled trial. European Journal of Pain, 28 (1), 127–139. 10.1002/ejp.2168
Summary
Keywords
magnesium sulfate, spinal surgery, meta-analysis, postoperative pain, opioid consumption, systematic review, anesthesia
Citation
Jin Z and Zhao J (2025) Effectiveness and impact of intravenous magnesium sulfate in spinal surgery systematic review and meta-analysis. Front. Pharmacol. 16:1624119. doi: 10.3389/fphar.2025.1624119
Received
07 May 2025
Accepted
28 May 2025
Published
18 June 2025
Volume
16 - 2025
Edited by
Francisco Lopez-Munoz, Camilo José Cela University, Spain
Reviewed by
Sakarie Mustafe Hidig, Zhejiang University, China
Alshaimaa Abdel Fattah Kamel, Zagazig University, Egypt
Updates
Copyright
© 2025 Jin and Zhao.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Zhaoguo Jin, linping0881@163.com
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.