Perioperative pain management remains a critical but challenging goal for the practicing anesthesiologist. It often includes the use of intravenous opioids, which offer rapid-acting and strong pain relief for the patient.1 However, opioids are associated with post-operative ileus, nausea, vomiting, shivering, urinary retention, and, importantly, dependence and addiction.2 Thus, there has been an emphasis on identifying non-opioid adjuncts to mitigate or augment the effects of opioids.1 One adjunctive pharmacotherapy which has demonstrated promise in multimodal strategies for perioperative pain management is intravenous magnesium.3
Intravenous magnesium, in the form of magnesium sulfate (MgSO4) is a multi-purpose compound with analgesic, anticonvulsant, and multiple cardiac effects.4 A 2024 systematic review and meta-analysis of 31 studies yielded data suggesting that intravenous magnesium creates greater early (6-hours post-operative) and late (up to 24 hours post-operative) pain management compared to control in general abdominal surgeries (mean pain score 3.1 ± 1.4 vs 4.2 ± 2.3 at 6-hours post-operative for magnesium vs control, respectively with a mean difference [MD]= -1.04; 95% confidence interval [CI] -1.52, -0.55; p <0.0001) (mean pain score 2.3 ± 1.1 vs 2.7 ± 1.5 at the secondary time point for magnesium vs control, respectively with a MD= =0.72; 95% CI -0.99, -0.44; p <0.0001).5 This same study also yielded data demonstrating a reduction in both early- (9.7 ± 7.7 morphine milligram equivalents [MME] vs 12.4 ± 8.4 MME, respectively with a MD = -2.75; 95% CI -4.20, -1.29; p = 0.0002) and late-cumulative post-operative opioid consumption (19.4 ± 12.4 MME vs 27.0 ± 16.2 MME, respectively with a MD = -5.81; 95% CI -9.09, -2.52; p = 0.0005) in magnesium treated groups compared with control groups.5 These data are further supported by a 2012 meta-analysis which produced data suggesting the use of perioperative intravenous magnesium, when compared to placebo, resulted in a 24.4% reduction in cumulative intravenous morphine consumption at 24 hours following surgery (MD 7.6 mg; 95% CI -9.5, -5.8; p <0.00001).6 These studies suggest that intravenous magnesium may be a useful component of multimodal perioperative pain management that effectively reduces pain while also reducing the usage and associated risks of opioid analgesics.
Another systematic review of randomized controlled trials that evaluated the use of magnesium in orthopedic surgery produced data suggesting a decrease in opioid-related adverse side effects in magnesium-treated groups when compared to a control group. Specifically, these side effects were post-operative nausea (relative risk [RR] 0.32; 95% CI 0.12, 0.82), vomiting (RR 0.38; 95% CI 0.15, 0.92), and shivering (RR 0.31; 95% CI 0.11, 0.88).7 A 2020 retrospective propensity score-matched analysis also yielded data suggesting the use of magnesium resulted in fewer opioid-related adverse side effects during total knee arthroplasty. The data demonstrated a lower incidence of post-operative urinary retention (odds ratio [OR] 0.49; 95% CI 0.29, 0.83).8
In conclusion, intravenous magnesium sulfate is a useful opioid-adjunct when used to reduce post-operative pain and overall opioid burden. While efficacious in its capacity to enhance post-operative pain control, it is also associated with a lower risk of opioid-related adverse side effects, including post-operative urinary retention, nausea, and shivering. Thus, intravenous magnesium appears to be a promising adjunct in multimodal perioperative pain management.
References
1. Pyati S, Gan TJ. Perioperative Pain Management: CNS Drugs. 2007;21(3):185-211. doi:10.2165/00023210-200721030-00002
2. Adams TJ, Aljohani DM, Forget P. Perioperative opioids: a narrative review contextualising new avenues to improve prescribing. Br J Anaesth. 2023;130(6):709-718. doi:10.1016/j.bja.2023.02.037
3. Lopez-Ruiz AA, Trinchet LP, Morozowich S, Misra L. The Efficacy of Magnesium Sulfate in Perioperative Multimodal Analgesia. Curr Pain Headache Rep. 2025;29(1):88. doi:10.1007/s11916-025-01395-y
4. PubChem. Magnesium Sulfate. Natl Libr Med. https://pubchem.ncbi.nlm.nih.gov/compound/Magnesium-Sulfate#section=Information-Sources
5. Avci Y, Rajarathinam M, Kalsekar N, et al. Unravelling the analgesic effects of perioperative magnesium in general abdominal surgery: a systematic review and meta-analysis of randomized controlled trials. Braz J Anesthesiol Engl Ed. 2024;74(4):844524. doi:10.1016/j.bjane.2024.844524
6. Albrecht E, Kirkham KR, Liu SS, Brull R. Peri‐operative intravenous administration of magnesium sulphate and postoperative pain: a meta‐analysis. Anaesthesia. 2013;68(1):79-90. doi:10.1111/j.1365-2044.2012.07335.x
7. Peng YN, Sung FC, Huang ML, Lin CL, Kao CH. The use of intravenous magnesium sulfate on postoperative analgesia in orthopedic surgery: A systematic review of randomized controlled trials. Medicine (Baltimore). 2018;97(50):e13583. doi:10.1097/MD.0000000000013583
8. Park JW, Kim EK, Lim D, Oh TK, Park S, Do SH. Magnesium Sulfate Treatment During Total Knee Arthroplasty Decreases Postoperative Urinary Retention: A Retrospective Propensity Score-Matched Analysis. J Clin Med. 2020;9(3):620. doi:10.3390/jcm9030620