Per the Natural Medicines database, adjunct intravenous (IV) magnesium sulfate may be effective for postoperative pain and the reduction of analgesic use postoperative. However, magnesium does not seem to improve muscle cramp frequency or intensity when given orally, nor appear to be beneficial in complex regional pain syndrome type 1 when given intravenously. There is insufficient reliable evidence to rate for acute or chronic back pain; cancer-related neuropathic pain; migraine treatment and prevention; nocturnal leg cramps; acute pain associated with kidney dysfunction; risk for chronic pain; and sore throat pain after endotracheal intubation. Notably, magnesium may largely interact with other drugs (e.g., antibiotics, anticoagulants) and supplements, as well as medical conditions. Intravenous magnesium is contraindicated in patients with heart block, and may contribute to a myasthenic crisis in patients with myasthenia gravis due to magnesium’s competition with calcium and inhibition of acetylcholine release. Magnesium may also affect platelet aggregation and theoretically increase risk of bleeding, although data is conflicting. Use of magnesium in patients who are pregnant or lactating is likely safe when used appropriately (i.e., doses below 350 mg daily), but high doses during pregnancy increases the risk of neonatal mortality and neurological defects. [1]
A 2024 narrative review discusses use of magnesium sulfate for postoperative pain in orthopedic surgery. The review aims to provide a comparison between intrathecal and IV administration of magnesium sulfate, particularly following orthopedic procedures. A comprehensive literature search was conducted which identified 4326 articles, with 9 randomized controlled trials included for analysis. The review found that intrathecal magnesium sulfate shows promise in postoperative pain management by delaying block onset and extending duration when used as an adjuvant to local anesthetics for spinal anesthesia. However, IV magnesium sulfate or intravenous dexmedetomidine were associated with faster onset of sensory and motor blockade in some studies. Both intrathecal and IV routes of magnesium sulfate administration seemed to improve postoperative analgesia outcomes, though the evidence on differences in effects was mixed. The review concluded that personalized choice of administration route, considering patient factors and surgery type, is important when using magnesium sulfate. Further research is still needed to better define optimal strategies and assess long-term outcomes, especially in orthopedic procedures. [2]
Numerous meta-analyses have been conducted to investigate efficacy of magnesium in various clinical settings, listed below:
A 2024 systematic review and meta-analysis compiled data from 31 randomized controlled trials, with 1762 participants being treated with IV magnesium or an inert control for postoperative pain after general abdominal surgery. Data were pooled to compare pain scores at 6 and 24 hours. Baseline characteristics were similar between magnesium and control groups across all individual trials, including a mean patient age of 49.4 years. Of the included patients, 44% underwent open surgical procedures while 46% underwent laparoscopic surgeries. The mean dose of magnesium sulfate administered within included studies was 41.1 ± 14.6 mg/kg (range: 3 to 50 mg/kg; 66% of studies continued magnesium infusion following the loading dose. Early postoperative pain scores (up to 6 hours) were assessed in 27 trials (n= 1,525 patients), suggesting significantly lower pain scores in the magnesium group compared to control (early mean score 3.1 ± 2.5 with magnesium vs. 4.1 ± 2.8 with control; mean difference [MD] -1.04, 95% confidence interval [CI] -1.52 to -0.55; p<0.0001; I2= 94%). When removing major outlying studies, the MD decreased to -0.56, but the difference remained statistically significant. Late postoperative pain scores (up to 24 hours) were assessed in 23 trials (n= 1,297 patients), again revealing a significantly lower mean pain score in the magnesium group (-0.41, 95% CI -0.67 to -0.14; p= 0.006; I2= 87%). Other outcomes assessed including opioid consumption, incidence of shivering, and time to rescue analgesia, were all found to be reduced with use of magnesium, suggesting use of adjunctive magnesium in perioperative protocols may improve patient comfort and postoperative outcomes. [3]
A 2024 systematic review and meta-analysis evaluated the efficacy and safety of IV magnesium sulfate in spinal surgery compared to alternatives. Data were compiled from 8 studies, comprising 541 patients, of which 245 were treated with magnesium, 143 with placebo, 93 with dexamethasone, and 60 with dexmedetomidine. Mean patient age within the studies ranged from 35.2 to 55.9 years; studies were conducted in Turkey, India, Korea, Belgium, and Greece. While no differences were found between groups for global visual analog scale score or pain score at 6 and 12 hours, magnesium was associated with significantly greater reduction in pain compared to all controls as a group at 24 hours (MD -0.20, 95% CI -0.39 to -0.02), based on data from 5 studies (n= 476 participants). The reduction in global VAS was significant compared to placebo at both 12 (MD -0.52) and 24 (MD -0.39) hours, but no significant differences were found compared to dexmedetomidine or dexamethasone. Most of the included studies also reported incidence of adverse events, finding a significantly higher rate of hypotension in the magnesium group compared to the control group collectively (odds ratio [OR] 1.97, 95% CI 1.10 to 3.52). No differences were found between magnesium and placebo or dexmedetomidine individually, although incidence of hypotension was significantly lower with dexamethasone compared to magnesium (OR 2.19, 95% CI 1.10 to 4.36). No significant differences were observed between magnesium and control groups for nausea and vomiting (PONV; OR 0.74, 95% CI 0.44 to 1.23), although when assessing individual controls, magnesium was associated with significantly less incidence of PONV compared to placebo (OR 0.37, 95% CI 0.16 to 0.85), but comparable risk with dexamethasone. Overall, results of this meta-analysis suggest magnesium sulfate significantly reduced pain at 24 h and decreased the consumption of opioids, muscle relaxants, and remifentanil compared to placebo and other analgesics in the setting of spinal surgery. Pending further prospective studies, implementation of adjunct magnesium sulfate could improve patient recovery following spinal surgery. [4]
A 2024 meta-analysis investigated the effects of IV magnesium sulfate on postoperative recovery quality in adult surgical patients. Seven randomized controlled trials with a total of 622 participants were included. Magnesium sulfate demonstrated significant improvement in global Quality of Recovery (QoR) score on postoperative day 1 (standardized mean difference [SMD]: 1.24; 95% CI; 0.70 to 1.78; p<0.00001). There was also a significant effect on pain (SMD 1; p<0.00001) and physical comfort (SMD 0.85; p<00001), emotional state (SMD 0.65 p= 0.002) and physical independence (SMD 0.43; p<0.00001). However, extubation time was unaffected and time in the post-anesthesia care unit was slightly longer in the magnesium sulfate group. Overall, the findings seem to favor magnesium sulfate as an adjunct for multimodal analgesia and enhancing recovery. However, there was notable high heterogeneity between studies, likely due to the variations between surgeries and the studies mainly represented short-duration surgeries that are less complex. [5]
Another 2024 meta-analysis evaluated the analgesic efficacy of magnesium sulfate as an adjuvant to the analgesic cocktail in total knee arthroplasty (TKA). Five randomized controlled trials involving 432 patients were included. Meta-analyses found that magnesium sulfate significantly reduced visual analog scale (VAS) pain scores at rest at 6, 12, and 24 hours postoperatively and VAS pain scores with motion at 12, 24, and 48 hours postoperatively compared to the control groups (overall effect p= 0.05). magnesium sulfate also significantly decreased total morphine consumption within 24 hours, from 24-48 hours, and during hospitalization. Time to first rescue analgesia was significantly shorter in the magnesium sulfate groups. Range of motion on postoperative day 1 and daily mobilization distance on postoperative day 1 were significantly greater with magnesium sulfate, while hospital length of stay was significantly shorter. No significant differences were found between groups in postoperative nausea and vomiting, wound complications, deep vein thrombosis, chronic pain, pruritus, or sedation. In conclusion, magnesium sulfate is an effective adjuvant analgesic that provides improvements in pain scores, opioid use, function, and length of stay when added to the analgesic cocktail for TKA. [6]
A 2023 network meta-analysis compared the efficacy of various nonopioid analgesic regimens for improving postoperative outcomes in adult cardiac surgical patients, including magnesium sulfate. A total of 124 randomized controlled trials involving over 26,000 patients were included for analysis. Magnesium sulfate’s effect on postoperative pain score was represented among 323 patients which observed a significant reduction in 24-hour pain scores (-0.05 points; 95% CI -0.07 to -0.02; high confidence). Magnesium sulfate also significantly decreased intensive care unit length of stay and reduced the risk of myocardial infarction. However, no treatments significantly impacted the secondary outcomes of delirium, nausea or vomiting. In conclusion, magnesium sulfate demonstrated promise and should be further assessed in larger clinical trials. [7]
A 2021 meta-analysis evaluated the effectiveness of magnesium sulfate as an adjunct to different anesthetic regimens in reducing postoperative pain in women undergoing cesarean section delivery. A total of 14 randomized controlled trials (N= 880 women) were included for analysis. There was a statistically significant effect compared to the control group on the highest VAS (WMD -0.74, 95% CI: -1.03 to -0.46, p<0.001) and the last VAS (WMD -0.47, 95% CI: -0.71 to -0.23, p<0.001). However, there were also a high degree of heterogeneity between study groups. Magnesium sulfate also increased time to analgesia requirements while decreasing the amount of analgesia consumed compared to the control group. There was no increase in adverse effects reported with magnesium sulfate use. The meta-analysis appears to demonstrate a significant improvement in pain scores with the addition of magnesium sulfate during cesarean section delivery. [8]
A 2021 systematic review and meta-analysis investigated efficacy and safety of adjunct intra articular (IA) magnesium plus local anesthetic for postoperative pain relief after arthroscopic knee surgery. Total, 11 randomized controlled trials were included, comprising 677 participants, although the studies were mostly conducted in Asia and North Africa. Mean patient ages in the studies ranged from 25 to 48 years. Pain VAS scores at rest were documented in 9 studies, revealing magnesium was associated with significantly lower VAS scores at several time points from 2, 4, 12, and 24 hours postoperatively. Pain VAS scores with movement were assessed in 7 trials, with magnesium again being associated with significantly lower VAS at 2 to 24 hours. Additionally, magnesium was associated with significantly less opioid consumption within 24 hours (MD -4.23, 95% CI -4.64 to -3.82) and significantly prolonged time to first analgesic (MD 329.99; 95% CI 228.73 to 431.24). Adverse reactions were reported in 3 studies, finding incidence of shivering, knee effusion, hypotension, and bradycardia, although no significant differences were observed between the comparable groups in each trial. [9]
A meta-analysis of perioperative systemic magnesium and its role in postoperative pain outcomes consisted of twenty randomized control trials involving a total sample population of 1,257 patients. Pooled results showed decreased pain scores ≤4 hours postoperatively (mean difference [MD] -0.74; 99% confidence interval [CI] -1.08 to -0.48) and ≤24 hours postoperatively (MD -0.36; 99% CI -0.63 to -0.09) versus control. Overall opioid consumption was largely decreased in the magnesium group compared to placebo (MD -10.52; 99% CI -13.50 to -7.54). The authors noted significant heterogeneity between some of the studies. [10]
Though not well understood, it is thought that the analgesic mechanism of magnesium comes from magnesium blocking the N-methyl-D-aspartate (NMDA) receptor and its associated ion channels. Glutamate, the natural analog of NDMA receptors, facilitates the transmission of nociceptive signals in acute and long-term pain conditions. Nociceptive impulses are transmitted from the dorsal horn of the spinal cord, through the ascending pathways of the spinal cord to the brain where pain is perceived. Another proposed mechanism is the inhibition of the inflammatory response through the reduction of inflammatory cytokines. Most of the studies in this review used a bolus dose ranging from 30 to 50 mg/kg, with a continuous infusion of 8 to 15 mg/kg/hour for a total of 4 to 6 hours. [11]