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Unravelling the analgesic effects of perioperative magnesium in general abdominal surgery: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background

Prior research has established the effectiveness of magnesium in relieving postoperative pain. This article aims to evaluate magnesium sulfate for perioperative analgesia in adults undergoing general abdominal surgery under general anesthesia.

Objective

The primary aim was to assess pain scores at 6 and 24 hours postoperatively in patients receiving magnesium sulfate vs. the control group. Secondary outcomes were postoperative opioid consumption, perioperative complications, and time to rescue analgesia.

Methods

A comprehensive database search identified studies comparing magnesium sulfate with control in adults undergoing general anesthesia for general abdominal surgery. Using random-effects models, data were presented as mean ± Standard Deviation (SD) or Odds Ratios (OR) with corresponding 95% Confidence Intervals (95% CI). A two-sided p-value < 0.05 was considered statistically significant.

Results

In total, 31 studies involving 1762 participants met the inclusion criteria. The magnesium group showed significantly lower postoperative pain scores at both early (within six hours) and late (up to 24 hours) time points compared to the control group. The early mean score was 3.1 ± 1.4 vs. 4.2 ± 2.3, and the late mean score was 2.3 ± 1.1 vs. 2.7 ± 1.5, resulting in an overall Mean Difference (MD) of −0.72; 95% CI −0.99, −0.44; p < 0.00001. The magnesium group was associated with lower rates of postoperative opioid consumption and shivering and had a longer time to first analgesia administration compared to the saline control group.

Conclusion

Magnesium sulfate administration was linked to reduced postoperative pain and opioid consumption following general abdominal surgery.

KEYWORDS
Acute pain; Postoperative pain; Magnesium sulphate; Abdominal surgery; Anesthesia; Analgesia

Introduction

Effective pain management is a critical objective in both anesthesia and perioperative care. Magnesium modulates pain by inhibiting the N-methyl-D-aspartate receptor, impeding calcium entry into the cell.11 Lysakowski C, Dumont L, Czarnetzki C, Tramèr MR. Magnesium as an Adjuvant to Postoperative Analgesia: A Systematic Review of Randomized Trials. Anesth Analg. 2007;104:1532-9.,22 Iseri LT, French JH. Magnesium: Nature's physiologic calcium blocker. Am Heart J. 1984;108:188-93. Previous clinical trials have affirmed the efficacy of magnesium sulfate in diminishing postoperative pain when juxtaposed with saline control.11 Lysakowski C, Dumont L, Czarnetzki C, Tramèr MR. Magnesium as an Adjuvant to Postoperative Analgesia: A Systematic Review of Randomized Trials. Anesth Analg. 2007;104:1532-9.,33 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.,44 Beckham T. Perioperative Use of Intravenous Magnesium Sulfate to Decrease Postoperative Pain. J Anesth Intensive Care Med. 2020;10(3). While using magnesium sulfate has demonstrated a reduction in postoperative opioid requirements, the optimal dosing regimen remains uncertain.33 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.,44 Beckham T. Perioperative Use of Intravenous Magnesium Sulfate to Decrease Postoperative Pain. J Anesth Intensive Care Med. 2020;10(3).

Prior reviews exploring magnesium as an analgesic adjunct encompassed a spectrum of surgeries characterized by diverse anticipated postoperative pain severities. This systematic review focuses on evaluating the effectiveness of magnesium sulfate for perioperative analgesia in adults undergoing General Anesthesia (GA) for general abdominal surgery and comparing it with an inert control. The primary objective is to assess postoperative pain scores in the group administered magnesium sulfate compared to the control. Secondary outcomes encompass postoperative opioid consumption, intraoperative complications, time to rescue analgesia, and postoperative side effects.

Methods

This systematic review and meta-analysis followed a predefined protocol, registered with PROSPERO (CRD42022326263), and adhered to PRISMA reporting Guidelines.55 Moher D. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Ann Intern Med. 2009;151:264.

Study selection

We included Randomized Controlled Trials (RCTs) involving Intravenous (IV) magnesium sulfate administration (bolus, infusion, or combination) for perioperative analgesia in adults undergoing general abdominal surgeries under General Anesthesia (GA). Exclusions comprised cohort studies, meta-analyses, systematic reviews, case reports, case series, abstracts, conference proceedings, studies not in English, investigations with non-IV magnesium administration, and those lacking a separate magnesium study arm. Postoperative pain scores (Numerical Rating Scale - NRS) were assessed at early (within 6 hours) and late (up to 24 hours) time points. Side effects and complications related to magnesium sulfate, were recorded in the Operating Room (OR) and/or Postanesthetic Care Unit (PACU). Cumulative postoperative opioid consumption was converted to Morphine Milligram Equivalents (MME) and measured at early and late time points.

Search strategy

A comprehensive search across PubMed, Medline, Embase, Web of Science, and Cochrane databases used the National Center for Biotechnology Information Medical Subject Headings (NCBI MeSH) descriptors [magnesium (mh) or magnesium (tw) or magnesium sulfate (mh) or magnesium sulfate (tw) or magnesium sulphate (tw)] and [perioperative period (mh) or perioperative (tw) or intraoperative (tw) or intraoperative period (mh) or postoperative (tw) or postoperative period (mh)].

Executed in January 2022, the detailed literature search strategy is in Supplementary Table S1. Two independent authors (YS and NK) scrutinized titles and abstracts, and full texts were assessed by two reviewers (YS and MN). References in the included studies were manually searched. Trials were evaluated for bias using the Cochrane risk of bias tool, graded as “high risk”, “low risk”, or “unclear risk” of bias.66 Smith AF, Carlisle J. Reviews, systematic reviews and Anaesthesia. Anaesthesia. 2015;70:644-50.,77 Higgins JP, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. Wiley; 2011. GRADE methodology assessed evidence.88 Neumann I, Pantoja T, Peñaloza B, Cifuentes L, Rada G. El sistema GRADE: un cambio en la forma de evaluar la calidad de la evidencia y la fuerza de recomendaciones. Rev Med Chil. 2014;142:630-5.

Data extraction

A standardized protocol guided a data collection form for study characteristics, patient demographics, and intraoperative and postoperative data. Study characteristics were recorded, including the author's name and publication year. Preoperative data, such as age, sex, and Body Mass Index (BMI), were documented. Intraoperative and postoperative data included the type of surgery, duration, doses, and methods of administration of magnesium sulfate and the control, intraoperative complications (such as hypotension and bradycardia), postoperative pain scores (Numerical Rating Scale - NRS), postoperative opioid consumption, time to rescue analgesia, and the incidence of postoperative adverse effects (hypotension, bradycardia, shivering, and Postoperative Nausea and Vomiting [PONV]). Two investigators (YS and YA) extracted data and compiled the results. Any discrepancies in data collection were solved by discussion and dialogue among the team members and by consulting the expert author (MN). Whenever data was missing, we made a concerted effort to contact the corresponding author via email. Our analysis exclusively incorporates studies for which we received a response regarding missing data. YS, NK, and YA ensured data accuracy and completeness.

Outcome definition

Primary outcome: postoperative pain scores (Numerical Rating Scale - NRS) in magnesium sulfate vs. control groups. Secondary outcomes: postoperative opioid consumption, time to rescue analgesia, intraoperative complications (hypotension, bradycardia), and postoperative side effects (hypotension, bradycardia, shivering, PONV).

Statistical analysis

Continuous data were presented as mean and standard deviation (SD) and compared as Mean Differences (MD) and 95% Confidence Interval (95% CI); dichotomous data were presented as Odds Ratios (ORs) and 95% CI; p < 0.05 was considered significant. A random-effects model accommodated inter-study variation. Egger's test, Begg's test, fail-safe N-test, and funnel plot inspection assessed publication bias. Statistical heterogeneity used the I2 statistic and Chi-Square test (I2 > 50%, and p < 0.05 indicated significant heterogeneity).99 Higgins JPT. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557-60. Sensitivity and influence analysis was conducted to explore and address heterogeneity by excluding outliers and recalculating pooled estimates. Subgroup and meta-regression analysis was performed to adjust for patient baseline and clinical characteristics to confirm the outcome of the pooled estimate. Review Manager Software (RevMan, V.5.4.1) and comprehensive metanalysis software version 3.0 were used to conduct the analysis.

Results

Our initial search identified 2320 studies, which underwent screening by titles and abstracts, resulting in 248 studies for full-text eligibility review. Ultimately, 31 studies with 1762 participants (800 patients in the MgSO4 group and 802 patients in the control group) met the inclusion criteria and were included in the analysis (Figure 1).1010 Zarauza R, Sáez-Fernández AN, Iribarren MJ, et al. A Comparative Study with Oral Nifedipine, Intravenous Nimodipine, and Magnesium Sulfate in Postoperative Analgesia. Anesth Analg. 2000;91:938-43.

11 Wilder-Smith CH, Knöpfli R, Wilder-Smith OH. Perioperative magnesium infusion and postoperative pain. Acta Anaesthesiol Scand. 1997;41:1023-7.

12 Tramer MR, Schneider J, Marti RA, Rifat K. Role of Magnesium Sulfate in Postoperative Analgesia. Anesthesiology. 1996;84:340-7.

13 Tauzin-Fin P, Sesay M, Delort-Laval S, Krol-Houdek MC, Maurette P. Intravenous magnesium sulphate decreases postoperative tramadol requirement after radical prostatectomy. Eur J Anaesthesiol. 2006;23:1055-9.

14 Taheri A, Haryalchi K, Mansour Ghanaie M, Habibi Arejan N. Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia. Anesthesiol Res Pract. 2015;2015.

15 Sousa AM, Rosado GMC, Neto JDS, Guimarães GMN, Ashmawi HA. Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: A double-blind randomized controlled trial. J Clin Anesth. 2016;34:379-84.

16 Singhvi B, Goyal G. Study the effect of a single dose of intravenous magnesium sulphate on postoperative pain after lower abdominal surgery. Inter J Med Res Professionals. 2020;57:57-62.

17 Shamim A, Salman W, Gul S. Effect of Magnesium Sulphate on postoperative pain in laparoscopic cholecystectomy. Int J Adv Res (Indore). 2015;3:813-8.

18 Seyhan TO, Tugrul M, Sungur MO, et al. Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery. Br J Anaesth. 2006;96:247-52.

19 Saadawy IM, Kaki AM, Abd El Latif AA, Abd-Elmaksoud AM, Tolba OM. Lidocaine vs. magnesium: Effect on analgesia after a laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2010;54:549-56.

20 Ryu JH, Koo BW, Kim BG, et al. Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles. Surg Endosc. 2016;30:4976-84.

21 Rafiq W, Kumar Fotedar K, Wasim D, Resident RS. A Prospective randomized single Blinded controlled study to evaluate the effect of single dose of magnesium sulphate on Postoperative analgesia in abdominal Surgeries patients receiving balanced general anaesthesia. J Med Sci Clin Res. 2018;06:798-807.

22 Ryu JH, Kang MH, Park KS, Do SH. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth. 2008;100:397-403.

23 Park JY, Hong JH, Kim DH, Yu J, Hwang JH, Kim YK. Magnesium and bladder discomfort after transurethral resection of bladder tumor: A randomized, double-blind, placebo-controlled study. Anesthesiology. 2020;133:64-77.

24 Olgun B, Oǧuz GO, Kaya M, Şalvi S, Eskiçirak HE, Güney I, et al. The effects of magnesium sulphate on desflurane requirement, early recovery and postoperative analgesia in laparascopic cholecystectomy. Magnes Res. 2012;25:72-8.

25 Moon S, Lim S, Yun J, et al. Additional effect of magnesium sulfate and vitamin C in laparoscopic gynecologic surgery for postoperative pain management: a double-blind randomized controlled trial. Anesth Pain Med (Seoul). 2020;15:88-95.

26 Moharari RS, Motalebi M, Najafi A, et al. Magnesium can decrease postoperative physiological ileus and postoperative pain in major non laparoscopic gastrointestinal surgeries: A randomized controlled trial. Anesth Pain Med. 2014;4:e12750.

27 Mentes O, Harlak A, Yigit T, et al. Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2008;52:1353-9.

28 Mavrommati PD, Gabopoulou ZT, Papadimos CN, et al. The perioperative infusion of low doses of magnesium sulfate reduces analgesic requirements in patients undergoing abdominal hernioplasty. Acute Pain. 2004;5:81-7.

29 Lu J, Wang JF, Guo CL, Yin Q, Cheng W, Qian B. Intravenously injected lidocaine or magnesium improves the quality of early recovery after laparoscopic cholecystectomy: A randomised controlled trial. Eur J Anaesthesiol. 2021;38(Suppl 1):S1-S8.

30 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.

31 Kocman IB, Krobot R, Premuzić J, et al. The effect of preemptive intravenous low-dose magnesium sulfate on early postoperative pain after laparoscopic cholecystectomy. Acta Clin Croat. 2013;52:289-94.

32 Kizilcik N, Koner O. Magnesium Sulfate Reduced Opioid Consumption in Obese Patients Undergoing Sleeve Gastrectomy: a Prospective, Randomized Clinical Trial. Obes Surg. 2018;28:2783-8.

33 Kiran S, Gupta R, Verma D. Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery. Indian J Anaesth. 2011;55:31-5.

34 Kim HY, Lee SY, Lee HS, Jun BK, Choi JB, Kim JE. Beneficial Effects of Intravenous Magnesium Administration During Robotic Radical Prostatectomy: A Randomized Controlled Trial. Adv Ther. 2021;38:1701-12.

35 Kaya S, Kararmaz A, Gedik R, Turhanoğlu S. Magnesium sulfate reduces postoperative morphine requirement after remifentanil-based anesthesia. Med Sci Monit. 2009;15:PI5-9.

36 Dautaj B, Bulku E, Jaho E, et al. Effectivness of dexametasone vs. Magnesium sulphate in postoperative analgesia: Dexametasone vs. Magnesium sulphate. Serbian Journal of Anesthesia and Intensive Therapy. 2016;38:69-73.

37 Bhatia A, Kashyap L, Pawar DK, Trikha A. Effect of intraoperative magnesium infusion on perioperative analgesia in open cholecystectomy. J Clin Anesth. 2004;16:262-5.

38 Ayoglu H, Karadeniz U, Kunduracilar Z, Ayoglu FN, Erdemli O. The analgesic effect of magnesium sulfate and ketamine in patients undergoing laparoscopic cholecystectomy. Pain Clinic. 2005;17:45-53.

39 Asadollah S, Vahdat M, Yazdkhasti P, Nikravan N. The effect of magnesium sulphate on postoperative analgesia requirements in gynecological surgeries. Turk Jinekoloji ve Obstetrik Dernegi Dergisi. 2015;12:34-7.
-4040 Arıkan M, Aslan B, Arıkan O, Horasanlı E, But A. Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study. Acta Cir Bras. 2016;31:67-73. Participants in the included trials underwent various general abdominal surgeries under General Anesthesia (GA) and received either magnesium sulfate or a control perioperatively. Supplementary Table S2 summarizes the data on the baseline patient characteristics. The quality of the studies was assessed using the Cochrane risk of bias tool, revealing some risks of bias in at least one domain for all studies (Figure 2). The GRADE evidence is summarized in Table 1.

Figure 1
PRISMA flow diagram (n, number).

Figure 2
Cochrane risk of bias assessment. Green, Low risk; Yellow, Unclear risk; Red, High risk.

Table 1
GRADE Evidence.

The baseline characteristics were similar between the magnesium and control groups across all individual trials, with no notable variances in patient age (800 vs. 802 patients, 49.4 ± 12.2 vs. 49.4 ± 12.9 years, p = 0.93), BMI (215 vs. 218 patients, 28.9 ± 9.3 vs. 28.8 ± 11.4 kg.m−2, p = 0.57), or surgery duration (697 vs. 696 patients, 111 ± 71.8 vs. 114 ± 70.7 minutes, p = 0.36). Fifty-four percent of patients underwent open surgical procedures, while 46% underwent laparoscopic surgeries. The mean magnesium sulfate administered in the studies analyzed in our meta-analysis was 41.1 ± 14.6 mg.kg−1 (ranging from 3 to 50 mg.kg−1). Sixty-six percent of these studies continued with continuous magnesium infusion following the initial loading dose. The Systematic Review (SR) of the included studies is summarized in Supplementary Table S3.

Early postoperative pain score

Twenty-seven trials, consisting of 1525 patients, contributed to the analysis of early (up to 6 hours) postoperative pain scores, indicating a significantly lower mean score in the magnesium group (n = 762, 3.1 ± 2.5) compared to the control group (n = 763, 4.1 ± 2.8) (MD = -1.04; 95% CI: -1.52, -0.55; p < 0.0001; I2 = 94%) (Figure 3 A).1010 Zarauza R, Sáez-Fernández AN, Iribarren MJ, et al. A Comparative Study with Oral Nifedipine, Intravenous Nimodipine, and Magnesium Sulfate in Postoperative Analgesia. Anesth Analg. 2000;91:938-43.

11 Wilder-Smith CH, Knöpfli R, Wilder-Smith OH. Perioperative magnesium infusion and postoperative pain. Acta Anaesthesiol Scand. 1997;41:1023-7.
-1212 Tramer MR, Schneider J, Marti RA, Rifat K. Role of Magnesium Sulfate in Postoperative Analgesia. Anesthesiology. 1996;84:340-7.,1414 Taheri A, Haryalchi K, Mansour Ghanaie M, Habibi Arejan N. Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia. Anesthesiol Res Pract. 2015;2015.

15 Sousa AM, Rosado GMC, Neto JDS, Guimarães GMN, Ashmawi HA. Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: A double-blind randomized controlled trial. J Clin Anesth. 2016;34:379-84.

16 Singhvi B, Goyal G. Study the effect of a single dose of intravenous magnesium sulphate on postoperative pain after lower abdominal surgery. Inter J Med Res Professionals. 2020;57:57-62.
-1717 Shamim A, Salman W, Gul S. Effect of Magnesium Sulphate on postoperative pain in laparoscopic cholecystectomy. Int J Adv Res (Indore). 2015;3:813-8.,1919 Saadawy IM, Kaki AM, Abd El Latif AA, Abd-Elmaksoud AM, Tolba OM. Lidocaine vs. magnesium: Effect on analgesia after a laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2010;54:549-56.

20 Ryu JH, Koo BW, Kim BG, et al. Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles. Surg Endosc. 2016;30:4976-84.

21 Rafiq W, Kumar Fotedar K, Wasim D, Resident RS. A Prospective randomized single Blinded controlled study to evaluate the effect of single dose of magnesium sulphate on Postoperative analgesia in abdominal Surgeries patients receiving balanced general anaesthesia. J Med Sci Clin Res. 2018;06:798-807.

22 Ryu JH, Kang MH, Park KS, Do SH. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth. 2008;100:397-403.

23 Park JY, Hong JH, Kim DH, Yu J, Hwang JH, Kim YK. Magnesium and bladder discomfort after transurethral resection of bladder tumor: A randomized, double-blind, placebo-controlled study. Anesthesiology. 2020;133:64-77.

24 Olgun B, Oǧuz GO, Kaya M, Şalvi S, Eskiçirak HE, Güney I, et al. The effects of magnesium sulphate on desflurane requirement, early recovery and postoperative analgesia in laparascopic cholecystectomy. Magnes Res. 2012;25:72-8.

25 Moon S, Lim S, Yun J, et al. Additional effect of magnesium sulfate and vitamin C in laparoscopic gynecologic surgery for postoperative pain management: a double-blind randomized controlled trial. Anesth Pain Med (Seoul). 2020;15:88-95.

26 Moharari RS, Motalebi M, Najafi A, et al. Magnesium can decrease postoperative physiological ileus and postoperative pain in major non laparoscopic gastrointestinal surgeries: A randomized controlled trial. Anesth Pain Med. 2014;4:e12750.

27 Mentes O, Harlak A, Yigit T, et al. Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2008;52:1353-9.

28 Mavrommati PD, Gabopoulou ZT, Papadimos CN, et al. The perioperative infusion of low doses of magnesium sulfate reduces analgesic requirements in patients undergoing abdominal hernioplasty. Acute Pain. 2004;5:81-7.

29 Lu J, Wang JF, Guo CL, Yin Q, Cheng W, Qian B. Intravenously injected lidocaine or magnesium improves the quality of early recovery after laparoscopic cholecystectomy: A randomised controlled trial. Eur J Anaesthesiol. 2021;38(Suppl 1):S1-S8.

30 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.
-3131 Kocman IB, Krobot R, Premuzić J, et al. The effect of preemptive intravenous low-dose magnesium sulfate on early postoperative pain after laparoscopic cholecystectomy. Acta Clin Croat. 2013;52:289-94.,3333 Kiran S, Gupta R, Verma D. Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery. Indian J Anaesth. 2011;55:31-5.,3434 Kim HY, Lee SY, Lee HS, Jun BK, Choi JB, Kim JE. Beneficial Effects of Intravenous Magnesium Administration During Robotic Radical Prostatectomy: A Randomized Controlled Trial. Adv Ther. 2021;38:1701-12.,3636 Dautaj B, Bulku E, Jaho E, et al. Effectivness of dexametasone vs. Magnesium sulphate in postoperative analgesia: Dexametasone vs. Magnesium sulphate. Serbian Journal of Anesthesia and Intensive Therapy. 2016;38:69-73.

37 Bhatia A, Kashyap L, Pawar DK, Trikha A. Effect of intraoperative magnesium infusion on perioperative analgesia in open cholecystectomy. J Clin Anesth. 2004;16:262-5.

38 Ayoglu H, Karadeniz U, Kunduracilar Z, Ayoglu FN, Erdemli O. The analgesic effect of magnesium sulfate and ketamine in patients undergoing laparoscopic cholecystectomy. Pain Clinic. 2005;17:45-53.

39 Asadollah S, Vahdat M, Yazdkhasti P, Nikravan N. The effect of magnesium sulphate on postoperative analgesia requirements in gynecological surgeries. Turk Jinekoloji ve Obstetrik Dernegi Dergisi. 2015;12:34-7.
-4040 Arıkan M, Aslan B, Arıkan O, Horasanlı E, But A. Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study. Acta Cir Bras. 2016;31:67-73. Publication bias was investigated using a funnel plot (Figure 4), Begg's test (p = 0.774), Egger's test (p = 0.646), and fail-safe N-test (1991) for each parameter, which was not significant (Figure 4). The funnel plot identified six studies as the major outliers contributing to the heterogeneity. When these studies were excluded and the pooled estimate recalculated, the MD decreased from -1.02 to -0.56, 95%CI narrowed (-0.81, -0.30), and heterogeneity decreased from 95% to 77% without impacting the final inference of our result (p < 0.0001).

Figure 3
Meta-analysis of early (6 h) and late (24 h) postoperative pain in magnesium and control group patients undergoing surgery. The mean difference of each included study is plotted. Using the random effects model, a pooled estimate of overall mean difference (diamonds) and 95% Confidence Intervals (width of diamonds) summarizes the effect size. CI, Confidence Interval; IV, Inverse Variance.

Figure 4
Funnel Plot for the association of early (6 h) and late (24 h) postoperative pain in patients belonging to the magnesium versus the control group. No evidence for substantial publication bias was found in Begg's or Egger's tests. According to classic fail-safe N, missing studies were required to bring the p-value to more than alpha, suggesting the absence of publication bias. SE(MD), Standard Error of Mean Difference.

Late postoperative pain score

Twenty-three trials, consisting of 1297 patients, were included in the analysis of late (up to 24 hours) postoperative pain scores, revealing a significantly lower mean score in the magnesium group (n = 657, 2.3 ± 2.0) compared to the control group (n = 640, 2.9 ± 2.4) (MD = -0.41; 95% CI: -0.67, -0.14; p = 0.006; I2 = 87%) (Figure 3 B).1010 Zarauza R, Sáez-Fernández AN, Iribarren MJ, et al. A Comparative Study with Oral Nifedipine, Intravenous Nimodipine, and Magnesium Sulfate in Postoperative Analgesia. Anesth Analg. 2000;91:938-43.

11 Wilder-Smith CH, Knöpfli R, Wilder-Smith OH. Perioperative magnesium infusion and postoperative pain. Acta Anaesthesiol Scand. 1997;41:1023-7.
-1212 Tramer MR, Schneider J, Marti RA, Rifat K. Role of Magnesium Sulfate in Postoperative Analgesia. Anesthesiology. 1996;84:340-7.,1414 Taheri A, Haryalchi K, Mansour Ghanaie M, Habibi Arejan N. Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia. Anesthesiol Res Pract. 2015;2015.

15 Sousa AM, Rosado GMC, Neto JDS, Guimarães GMN, Ashmawi HA. Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: A double-blind randomized controlled trial. J Clin Anesth. 2016;34:379-84.
-1616 Singhvi B, Goyal G. Study the effect of a single dose of intravenous magnesium sulphate on postoperative pain after lower abdominal surgery. Inter J Med Res Professionals. 2020;57:57-62.,1919 Saadawy IM, Kaki AM, Abd El Latif AA, Abd-Elmaksoud AM, Tolba OM. Lidocaine vs. magnesium: Effect on analgesia after a laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2010;54:549-56.,2020 Ryu JH, Koo BW, Kim BG, et al. Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles. Surg Endosc. 2016;30:4976-84.,2222 Ryu JH, Kang MH, Park KS, Do SH. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth. 2008;100:397-403.,2424 Olgun B, Oǧuz GO, Kaya M, Şalvi S, Eskiçirak HE, Güney I, et al. The effects of magnesium sulphate on desflurane requirement, early recovery and postoperative analgesia in laparascopic cholecystectomy. Magnes Res. 2012;25:72-8.

25 Moon S, Lim S, Yun J, et al. Additional effect of magnesium sulfate and vitamin C in laparoscopic gynecologic surgery for postoperative pain management: a double-blind randomized controlled trial. Anesth Pain Med (Seoul). 2020;15:88-95.

26 Moharari RS, Motalebi M, Najafi A, et al. Magnesium can decrease postoperative physiological ileus and postoperative pain in major non laparoscopic gastrointestinal surgeries: A randomized controlled trial. Anesth Pain Med. 2014;4:e12750.
-2727 Mentes O, Harlak A, Yigit T, et al. Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2008;52:1353-9.,2929 Lu J, Wang JF, Guo CL, Yin Q, Cheng W, Qian B. Intravenously injected lidocaine or magnesium improves the quality of early recovery after laparoscopic cholecystectomy: A randomised controlled trial. Eur J Anaesthesiol. 2021;38(Suppl 1):S1-S8.

30 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.
-3131 Kocman IB, Krobot R, Premuzić J, et al. The effect of preemptive intravenous low-dose magnesium sulfate on early postoperative pain after laparoscopic cholecystectomy. Acta Clin Croat. 2013;52:289-94.,3333 Kiran S, Gupta R, Verma D. Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery. Indian J Anaesth. 2011;55:31-5.,3434 Kim HY, Lee SY, Lee HS, Jun BK, Choi JB, Kim JE. Beneficial Effects of Intravenous Magnesium Administration During Robotic Radical Prostatectomy: A Randomized Controlled Trial. Adv Ther. 2021;38:1701-12.,3636 Dautaj B, Bulku E, Jaho E, et al. Effectivness of dexametasone vs. Magnesium sulphate in postoperative analgesia: Dexametasone vs. Magnesium sulphate. Serbian Journal of Anesthesia and Intensive Therapy. 2016;38:69-73.

37 Bhatia A, Kashyap L, Pawar DK, Trikha A. Effect of intraoperative magnesium infusion on perioperative analgesia in open cholecystectomy. J Clin Anesth. 2004;16:262-5.

38 Ayoglu H, Karadeniz U, Kunduracilar Z, Ayoglu FN, Erdemli O. The analgesic effect of magnesium sulfate and ketamine in patients undergoing laparoscopic cholecystectomy. Pain Clinic. 2005;17:45-53.

39 Asadollah S, Vahdat M, Yazdkhasti P, Nikravan N. The effect of magnesium sulphate on postoperative analgesia requirements in gynecological surgeries. Turk Jinekoloji ve Obstetrik Dernegi Dergisi. 2015;12:34-7.
-4040 Arıkan M, Aslan B, Arıkan O, Horasanlı E, But A. Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study. Acta Cir Bras. 2016;31:67-73. No significant publication bias was observed (Figure 4). The funnel plot identified six studies as the major outliers contributing to the heterogeneity. When these studies were excluded and the pooled estimate recalculated, the MD decreased from -0.42 to -0.41, the 95% CI narrowed (-0.53, -0.29), and heterogeneity decreased from 87% to 11% without impacting the final inference of our result (p < 0.00001). The overall postoperative pain score data indicated MD = -0.72; 95% CI: -0.99, -0.44; p < 0.00001; I2 = 93%. Influence analysis confirmed the robustness of the results.

Early cumulative postoperative opioid consumption

Seventeen trials, consisting of 916 patients, contributed to the analysis of early (up to 6 hours) postoperative opioid consumption, demonstrating a significantly lower mean measurement in the magnesium group (n = 459, 9.7 ± 7.7 MME) compared to the control group (n = 457, 12.4 ± 8.4 MME) (MD = -2.75; 95% CI: -4.20, -1.29; p = 0.0002; I2 = 99%) (Figure 5).1010 Zarauza R, Sáez-Fernández AN, Iribarren MJ, et al. A Comparative Study with Oral Nifedipine, Intravenous Nimodipine, and Magnesium Sulfate in Postoperative Analgesia. Anesth Analg. 2000;91:938-43.

11 Wilder-Smith CH, Knöpfli R, Wilder-Smith OH. Perioperative magnesium infusion and postoperative pain. Acta Anaesthesiol Scand. 1997;41:1023-7.
-1212 Tramer MR, Schneider J, Marti RA, Rifat K. Role of Magnesium Sulfate in Postoperative Analgesia. Anesthesiology. 1996;84:340-7.,1515 Sousa AM, Rosado GMC, Neto JDS, Guimarães GMN, Ashmawi HA. Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: A double-blind randomized controlled trial. J Clin Anesth. 2016;34:379-84.,1717 Shamim A, Salman W, Gul S. Effect of Magnesium Sulphate on postoperative pain in laparoscopic cholecystectomy. Int J Adv Res (Indore). 2015;3:813-8.

18 Seyhan TO, Tugrul M, Sungur MO, et al. Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery. Br J Anaesth. 2006;96:247-52.

19 Saadawy IM, Kaki AM, Abd El Latif AA, Abd-Elmaksoud AM, Tolba OM. Lidocaine vs. magnesium: Effect on analgesia after a laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2010;54:549-56.

20 Ryu JH, Koo BW, Kim BG, et al. Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles. Surg Endosc. 2016;30:4976-84.

21 Rafiq W, Kumar Fotedar K, Wasim D, Resident RS. A Prospective randomized single Blinded controlled study to evaluate the effect of single dose of magnesium sulphate on Postoperative analgesia in abdominal Surgeries patients receiving balanced general anaesthesia. J Med Sci Clin Res. 2018;06:798-807.
-2222 Ryu JH, Kang MH, Park KS, Do SH. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth. 2008;100:397-403.,2525 Moon S, Lim S, Yun J, et al. Additional effect of magnesium sulfate and vitamin C in laparoscopic gynecologic surgery for postoperative pain management: a double-blind randomized controlled trial. Anesth Pain Med (Seoul). 2020;15:88-95.,2626 Moharari RS, Motalebi M, Najafi A, et al. Magnesium can decrease postoperative physiological ileus and postoperative pain in major non laparoscopic gastrointestinal surgeries: A randomized controlled trial. Anesth Pain Med. 2014;4:e12750.,2828 Mavrommati PD, Gabopoulou ZT, Papadimos CN, et al. The perioperative infusion of low doses of magnesium sulfate reduces analgesic requirements in patients undergoing abdominal hernioplasty. Acute Pain. 2004;5:81-7.,3030 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.,3232 Kizilcik N, Koner O. Magnesium Sulfate Reduced Opioid Consumption in Obese Patients Undergoing Sleeve Gastrectomy: a Prospective, Randomized Clinical Trial. Obes Surg. 2018;28:2783-8.,3434 Kim HY, Lee SY, Lee HS, Jun BK, Choi JB, Kim JE. Beneficial Effects of Intravenous Magnesium Administration During Robotic Radical Prostatectomy: A Randomized Controlled Trial. Adv Ther. 2021;38:1701-12.,3838 Ayoglu H, Karadeniz U, Kunduracilar Z, Ayoglu FN, Erdemli O. The analgesic effect of magnesium sulfate and ketamine in patients undergoing laparoscopic cholecystectomy. Pain Clinic. 2005;17:45-53.

Figure 5
Meta-analysis of early (6 h) and late (24 h) postoperative opioid consumption in magnesium and control group patients undergoing surgery. The mean difference of each included study is plotted. Using the random effects model, a pooled estimate of overall mean difference (diamonds) and 95% Confidence Intervals (width of diamonds) summarizes the effect size. CI, Confidence Interval; IV, Inverse Variance.

Late cumulative postoperative opioid consumption

Twenty-one trials, consisting of 991 patients, were included in the analysis of late (up to 24 hours) postoperative opioid consumption, indicating a significantly lower mean score in the magnesium group (n = 496, 19.4 ± 12.4 MME) compared to the control group (n = 496, 27.0 ± 16.2 MME) (MD = -8.46; 95% CI: -15.06, -1.87; p = 0.01; I2 = 100%) (Figure 5).1010 Zarauza R, Sáez-Fernández AN, Iribarren MJ, et al. A Comparative Study with Oral Nifedipine, Intravenous Nimodipine, and Magnesium Sulfate in Postoperative Analgesia. Anesth Analg. 2000;91:938-43.

11 Wilder-Smith CH, Knöpfli R, Wilder-Smith OH. Perioperative magnesium infusion and postoperative pain. Acta Anaesthesiol Scand. 1997;41:1023-7.

12 Tramer MR, Schneider J, Marti RA, Rifat K. Role of Magnesium Sulfate in Postoperative Analgesia. Anesthesiology. 1996;84:340-7.

13 Tauzin-Fin P, Sesay M, Delort-Laval S, Krol-Houdek MC, Maurette P. Intravenous magnesium sulphate decreases postoperative tramadol requirement after radical prostatectomy. Eur J Anaesthesiol. 2006;23:1055-9.
-1414 Taheri A, Haryalchi K, Mansour Ghanaie M, Habibi Arejan N. Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia. Anesthesiol Res Pract. 2015;2015.,1818 Seyhan TO, Tugrul M, Sungur MO, et al. Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery. Br J Anaesth. 2006;96:247-52.

19 Saadawy IM, Kaki AM, Abd El Latif AA, Abd-Elmaksoud AM, Tolba OM. Lidocaine vs. magnesium: Effect on analgesia after a laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2010;54:549-56.
-2020 Ryu JH, Koo BW, Kim BG, et al. Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles. Surg Endosc. 2016;30:4976-84.,2222 Ryu JH, Kang MH, Park KS, Do SH. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth. 2008;100:397-403.,2424 Olgun B, Oǧuz GO, Kaya M, Şalvi S, Eskiçirak HE, Güney I, et al. The effects of magnesium sulphate on desflurane requirement, early recovery and postoperative analgesia in laparascopic cholecystectomy. Magnes Res. 2012;25:72-8.

25 Moon S, Lim S, Yun J, et al. Additional effect of magnesium sulfate and vitamin C in laparoscopic gynecologic surgery for postoperative pain management: a double-blind randomized controlled trial. Anesth Pain Med (Seoul). 2020;15:88-95.

26 Moharari RS, Motalebi M, Najafi A, et al. Magnesium can decrease postoperative physiological ileus and postoperative pain in major non laparoscopic gastrointestinal surgeries: A randomized controlled trial. Anesth Pain Med. 2014;4:e12750.
-2727 Mentes O, Harlak A, Yigit T, et al. Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2008;52:1353-9.,3030 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.

31 Kocman IB, Krobot R, Premuzić J, et al. The effect of preemptive intravenous low-dose magnesium sulfate on early postoperative pain after laparoscopic cholecystectomy. Acta Clin Croat. 2013;52:289-94.
-3232 Kizilcik N, Koner O. Magnesium Sulfate Reduced Opioid Consumption in Obese Patients Undergoing Sleeve Gastrectomy: a Prospective, Randomized Clinical Trial. Obes Surg. 2018;28:2783-8.,3535 Kaya S, Kararmaz A, Gedik R, Turhanoğlu S. Magnesium sulfate reduces postoperative morphine requirement after remifentanil-based anesthesia. Med Sci Monit. 2009;15:PI5-9.

36 Dautaj B, Bulku E, Jaho E, et al. Effectivness of dexametasone vs. Magnesium sulphate in postoperative analgesia: Dexametasone vs. Magnesium sulphate. Serbian Journal of Anesthesia and Intensive Therapy. 2016;38:69-73.

37 Bhatia A, Kashyap L, Pawar DK, Trikha A. Effect of intraoperative magnesium infusion on perioperative analgesia in open cholecystectomy. J Clin Anesth. 2004;16:262-5.

38 Ayoglu H, Karadeniz U, Kunduracilar Z, Ayoglu FN, Erdemli O. The analgesic effect of magnesium sulfate and ketamine in patients undergoing laparoscopic cholecystectomy. Pain Clinic. 2005;17:45-53.
-3939 Asadollah S, Vahdat M, Yazdkhasti P, Nikravan N. The effect of magnesium sulphate on postoperative analgesia requirements in gynecological surgeries. Turk Jinekoloji ve Obstetrik Dernegi Dergisi. 2015;12:34-7. The overall postoperative opioid consumption data revealed MD = -5.81; 95% CI: -9.09, -2.52; p = 0.0005; I2 = 100%.

Time to rescue analgesia

Five trials with 268 patients contributed to the analysis of time to rescue analgesia, indicating significantly longer time in the magnesium group (n = 130, 196.0 ± 315.1 min) compared to the control group (n = 138, 121.0 ± 252.3 min) (MD = 21.45; 95% CI: 6.62, 36.28; p = 0.005; I2 = 96%) (Supplementary Fig. 1).1313 Tauzin-Fin P, Sesay M, Delort-Laval S, Krol-Houdek MC, Maurette P. Intravenous magnesium sulphate decreases postoperative tramadol requirement after radical prostatectomy. Eur J Anaesthesiol. 2006;23:1055-9.,1515 Sousa AM, Rosado GMC, Neto JDS, Guimarães GMN, Ashmawi HA. Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: A double-blind randomized controlled trial. J Clin Anesth. 2016;34:379-84.,1717 Shamim A, Salman W, Gul S. Effect of Magnesium Sulphate on postoperative pain in laparoscopic cholecystectomy. Int J Adv Res (Indore). 2015;3:813-8.,2121 Rafiq W, Kumar Fotedar K, Wasim D, Resident RS. A Prospective randomized single Blinded controlled study to evaluate the effect of single dose of magnesium sulphate on Postoperative analgesia in abdominal Surgeries patients receiving balanced general anaesthesia. J Med Sci Clin Res. 2018;06:798-807.,3030 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.

Intraoperative complications

For intraoperative hypotension (n = 375 patients) and bradycardia (n = 445 patients), six1212 Tramer MR, Schneider J, Marti RA, Rifat K. Role of Magnesium Sulfate in Postoperative Analgesia. Anesthesiology. 1996;84:340-7.,1818 Seyhan TO, Tugrul M, Sungur MO, et al. Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery. Br J Anaesth. 2006;96:247-52.,2020 Ryu JH, Koo BW, Kim BG, et al. Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles. Surg Endosc. 2016;30:4976-84.,2828 Mavrommati PD, Gabopoulou ZT, Papadimos CN, et al. The perioperative infusion of low doses of magnesium sulfate reduces analgesic requirements in patients undergoing abdominal hernioplasty. Acute Pain. 2004;5:81-7.,2929 Lu J, Wang JF, Guo CL, Yin Q, Cheng W, Qian B. Intravenously injected lidocaine or magnesium improves the quality of early recovery after laparoscopic cholecystectomy: A randomised controlled trial. Eur J Anaesthesiol. 2021;38(Suppl 1):S1-S8.,3333 Kiran S, Gupta R, Verma D. Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery. Indian J Anaesth. 2011;55:31-5. and seven trials,1212 Tramer MR, Schneider J, Marti RA, Rifat K. Role of Magnesium Sulfate in Postoperative Analgesia. Anesthesiology. 1996;84:340-7.,1818 Seyhan TO, Tugrul M, Sungur MO, et al. Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery. Br J Anaesth. 2006;96:247-52.,2020 Ryu JH, Koo BW, Kim BG, et al. Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles. Surg Endosc. 2016;30:4976-84.,2424 Olgun B, Oǧuz GO, Kaya M, Şalvi S, Eskiçirak HE, Güney I, et al. The effects of magnesium sulphate on desflurane requirement, early recovery and postoperative analgesia in laparascopic cholecystectomy. Magnes Res. 2012;25:72-8.,2929 Lu J, Wang JF, Guo CL, Yin Q, Cheng W, Qian B. Intravenously injected lidocaine or magnesium improves the quality of early recovery after laparoscopic cholecystectomy: A randomised controlled trial. Eur J Anaesthesiol. 2021;38(Suppl 1):S1-S8.,3333 Kiran S, Gupta R, Verma D. Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery. Indian J Anaesth. 2011;55:31-5.,3434 Kim HY, Lee SY, Lee HS, Jun BK, Choi JB, Kim JE. Beneficial Effects of Intravenous Magnesium Administration During Robotic Radical Prostatectomy: A Randomized Controlled Trial. Adv Ther. 2021;38:1701-12. respectively, were included in the meta-analysis, which showed no significant differences between the magnesium and control groups (OR = 1.52; 95% CI: 0.79-2.92; p = 0.90; I2 = 0% and OR = 0.91; 95% CI: 0.38-2.17; p = 0.82; I2 = 48%, respectively) (Supplementary Fig. 2).

Postoperative side effects: hypotension, bradycardia, PONV, shivering

Ten (n = 629 patients),1010 Zarauza R, Sáez-Fernández AN, Iribarren MJ, et al. A Comparative Study with Oral Nifedipine, Intravenous Nimodipine, and Magnesium Sulfate in Postoperative Analgesia. Anesth Analg. 2000;91:938-43.,1414 Taheri A, Haryalchi K, Mansour Ghanaie M, Habibi Arejan N. Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia. Anesthesiol Res Pract. 2015;2015.,1616 Singhvi B, Goyal G. Study the effect of a single dose of intravenous magnesium sulphate on postoperative pain after lower abdominal surgery. Inter J Med Res Professionals. 2020;57:57-62.,1818 Seyhan TO, Tugrul M, Sungur MO, et al. Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery. Br J Anaesth. 2006;96:247-52.,2323 Park JY, Hong JH, Kim DH, Yu J, Hwang JH, Kim YK. Magnesium and bladder discomfort after transurethral resection of bladder tumor: A randomized, double-blind, placebo-controlled study. Anesthesiology. 2020;133:64-77.,2828 Mavrommati PD, Gabopoulou ZT, Papadimos CN, et al. The perioperative infusion of low doses of magnesium sulfate reduces analgesic requirements in patients undergoing abdominal hernioplasty. Acute Pain. 2004;5:81-7.,3030 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.,3333 Kiran S, Gupta R, Verma D. Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery. Indian J Anaesth. 2011;55:31-5.,3535 Kaya S, Kararmaz A, Gedik R, Turhanoğlu S. Magnesium sulfate reduces postoperative morphine requirement after remifentanil-based anesthesia. Med Sci Monit. 2009;15:PI5-9.,4040 Arıkan M, Aslan B, Arıkan O, Horasanlı E, But A. Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study. Acta Cir Bras. 2016;31:67-73. seven (n = 427 patients),1010 Zarauza R, Sáez-Fernández AN, Iribarren MJ, et al. A Comparative Study with Oral Nifedipine, Intravenous Nimodipine, and Magnesium Sulfate in Postoperative Analgesia. Anesth Analg. 2000;91:938-43.,1616 Singhvi B, Goyal G. Study the effect of a single dose of intravenous magnesium sulphate on postoperative pain after lower abdominal surgery. Inter J Med Res Professionals. 2020;57:57-62.,1818 Seyhan TO, Tugrul M, Sungur MO, et al. Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery. Br J Anaesth. 2006;96:247-52.,3030 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.,3333 Kiran S, Gupta R, Verma D. Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery. Indian J Anaesth. 2011;55:31-5.,3535 Kaya S, Kararmaz A, Gedik R, Turhanoğlu S. Magnesium sulfate reduces postoperative morphine requirement after remifentanil-based anesthesia. Med Sci Monit. 2009;15:PI5-9.,4040 Arıkan M, Aslan B, Arıkan O, Horasanlı E, But A. Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study. Acta Cir Bras. 2016;31:67-73. twenty (n = 1134 patients),1010 Zarauza R, Sáez-Fernández AN, Iribarren MJ, et al. A Comparative Study with Oral Nifedipine, Intravenous Nimodipine, and Magnesium Sulfate in Postoperative Analgesia. Anesth Analg. 2000;91:938-43.

11 Wilder-Smith CH, Knöpfli R, Wilder-Smith OH. Perioperative magnesium infusion and postoperative pain. Acta Anaesthesiol Scand. 1997;41:1023-7.

12 Tramer MR, Schneider J, Marti RA, Rifat K. Role of Magnesium Sulfate in Postoperative Analgesia. Anesthesiology. 1996;84:340-7.

13 Tauzin-Fin P, Sesay M, Delort-Laval S, Krol-Houdek MC, Maurette P. Intravenous magnesium sulphate decreases postoperative tramadol requirement after radical prostatectomy. Eur J Anaesthesiol. 2006;23:1055-9.

14 Taheri A, Haryalchi K, Mansour Ghanaie M, Habibi Arejan N. Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia. Anesthesiol Res Pract. 2015;2015.

15 Sousa AM, Rosado GMC, Neto JDS, Guimarães GMN, Ashmawi HA. Magnesium sulfate improves postoperative analgesia in laparoscopic gynecologic surgeries: A double-blind randomized controlled trial. J Clin Anesth. 2016;34:379-84.
-1616 Singhvi B, Goyal G. Study the effect of a single dose of intravenous magnesium sulphate on postoperative pain after lower abdominal surgery. Inter J Med Res Professionals. 2020;57:57-62.,1919 Saadawy IM, Kaki AM, Abd El Latif AA, Abd-Elmaksoud AM, Tolba OM. Lidocaine vs. magnesium: Effect on analgesia after a laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2010;54:549-56.,2020 Ryu JH, Koo BW, Kim BG, et al. Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles. Surg Endosc. 2016;30:4976-84.,2222 Ryu JH, Kang MH, Park KS, Do SH. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth. 2008;100:397-403.,2323 Park JY, Hong JH, Kim DH, Yu J, Hwang JH, Kim YK. Magnesium and bladder discomfort after transurethral resection of bladder tumor: A randomized, double-blind, placebo-controlled study. Anesthesiology. 2020;133:64-77.,2525 Moon S, Lim S, Yun J, et al. Additional effect of magnesium sulfate and vitamin C in laparoscopic gynecologic surgery for postoperative pain management: a double-blind randomized controlled trial. Anesth Pain Med (Seoul). 2020;15:88-95.,2727 Mentes O, Harlak A, Yigit T, et al. Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2008;52:1353-9.,2929 Lu J, Wang JF, Guo CL, Yin Q, Cheng W, Qian B. Intravenously injected lidocaine or magnesium improves the quality of early recovery after laparoscopic cholecystectomy: A randomised controlled trial. Eur J Anaesthesiol. 2021;38(Suppl 1):S1-S8.

30 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.
-3131 Kocman IB, Krobot R, Premuzić J, et al. The effect of preemptive intravenous low-dose magnesium sulfate on early postoperative pain after laparoscopic cholecystectomy. Acta Clin Croat. 2013;52:289-94.,3535 Kaya S, Kararmaz A, Gedik R, Turhanoğlu S. Magnesium sulfate reduces postoperative morphine requirement after remifentanil-based anesthesia. Med Sci Monit. 2009;15:PI5-9.,3737 Bhatia A, Kashyap L, Pawar DK, Trikha A. Effect of intraoperative magnesium infusion on perioperative analgesia in open cholecystectomy. J Clin Anesth. 2004;16:262-5.,3838 Ayoglu H, Karadeniz U, Kunduracilar Z, Ayoglu FN, Erdemli O. The analgesic effect of magnesium sulfate and ketamine in patients undergoing laparoscopic cholecystectomy. Pain Clinic. 2005;17:45-53.,4040 Arıkan M, Aslan B, Arıkan O, Horasanlı E, But A. Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study. Acta Cir Bras. 2016;31:67-73. and five trials (n = 264 patients)1212 Tramer MR, Schneider J, Marti RA, Rifat K. Role of Magnesium Sulfate in Postoperative Analgesia. Anesthesiology. 1996;84:340-7.,2222 Ryu JH, Kang MH, Park KS, Do SH. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth. 2008;100:397-403.,3030 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.,3434 Kim HY, Lee SY, Lee HS, Jun BK, Choi JB, Kim JE. Beneficial Effects of Intravenous Magnesium Administration During Robotic Radical Prostatectomy: A Randomized Controlled Trial. Adv Ther. 2021;38:1701-12.,3737 Bhatia A, Kashyap L, Pawar DK, Trikha A. Effect of intraoperative magnesium infusion on perioperative analgesia in open cholecystectomy. J Clin Anesth. 2004;16:262-5. respectively were included in the analysis of postoperative hypotension, bradycardia, PONV, and shivering, indicating no significant differences between the magnesium and control groups (OR = 0.90; 95% CI: 0.47-1.72; p = 0.75; I2 = 0%; OR = 0.91; 95% CI: 0.38-2.17; p = 0.82; I2 = 48%; OR = 0.78; 95% CI: 0.59-1.09; p = 0.08; I2 = 56%, and OR = 0.19; 95% CI: 0.09-0.44; p < 0.0001; I2 = 0%, respectively) (Supplementary Fig. 3).

Sensitivity, subgroup and meta-regression analysis

We performed subgroup analysis regarding surgical type (laparotomy vs. laparoscopy: 14 studies vs. 12 studies: MD [95% CI]: -1.20 [-1.34, -1.06] vs. -0.63 [-0.79, -0.46]) and magnesium continuous infusion (yes vs. no: 17 studies vs. 9 studies: -0.85 [-1.43, -0.27] vs. -1.34 [-2.19, -0.48]). No significant differences were observed between these subgroups. In addressing baseline patient and clinical characteristic variations, we conducted a meta-regression analysis, considering factors such as age, gender, BMI, surgical duration, postoperative opioid use, and magnesium dosage as continuous variables. Moreover, we categorized surgical type (laparotomy versus laparoscopy) and magnesium continuous infusion (yes vs. no) to assess their impact on outcomes. Although these variables slightly affected the mean difference, they did not substantially influence the overall estimation of pain scores at 6 and 24 hours (refer to Supplementary Table S3). Additionally, we evaluated the stability of aggregated pain scores through influence analyses by systematically excluding each study from the dataset and recalculating aggregated pain scores based on the remaining studies (see Supplementary Fig. 4A and 4B).

Discussion

Effective postoperative pain management is crucial as it correlates with adverse clinical outcomes and patient dissatisfaction, potentially leading to chronic pain.4141 Mazda Y, Jadin S, Kahn JS. Postoperative pain management. Canadian J General Internal Med. 2021;16:5-17. Our findings underscore the beneficial impact of perioperative magnesium sulfate on postoperative pain outcomes, encompassing pain scores, opioid consumption, and adverse effects such as postoperative shivering in adults undergoing General Anesthesia (GA) for general abdominal surgery. Notably, the time to the first analgesic administration was prolonged in the magnesium group compared to the saline control. Importantly, no significant disparities were observed between the two groups concerning intraoperative complications and postoperative side effects, including hypotension, bradycardia, shivering, and Postoperative Nausea and Vomiting (PONV).

This study is distinctive as it represents the first systematic review and meta-analysis consolidating evidence from randomized control trials that specifically focus on the analgesic effects of magnesium sulfate for abdominal surgery. Previous systematic reviews have explored the relationship between magnesium and postoperative analgesia across various surgical disciplines, including orthopedic and cardiac surgery, alongside abdominal surgeries.11 Lysakowski C, Dumont L, Czarnetzki C, Tramèr MR. Magnesium as an Adjuvant to Postoperative Analgesia: A Systematic Review of Randomized Trials. Anesth Analg. 2007;104:1532-9.,33 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.,4242 De Oliveira GS, Castro-Alves LJ, Khan JH, McCarthy RJ. Perioperative Systemic Magnesium to Minimize Postoperative Pain. Anesthesiology. 2013;119:178-90.

43 Murphy JD, Paskaradevan J, Eisler LL, et al. Analgesic efficacy of continuous intravenous magnesium infusion as an adjuvant to morphine for postoperative analgesia: a systematic review and meta-analysis. Middle East J Anaesthesiol. 2013;22:11-20.
-4444 Guo BL, Lin Y, Hu W, et al. Effects of Systemic Magnesium on Post-operative Analgesia: Is the Current Evidence Strong Enough? Pain Physician. 2015;18:405-18. An earlier systematic review and meta-analysis on perioperative intravenous magnesium sulfate administration for postoperative pain also demonstrated a reduction in postoperative opioid consumption compared to control groups, indicating lower postoperative pain. Interestingly, the mode of delivery (bolus, bolus administration, or infusion) did not significantly impact outcomes, and the total magnesium dose administered did not correlate with 24 hour postoperative morphine requirements. Notably, a single bolus administration between 40 and 50 mg.kg−1 reduced postoperative morphine consumption.33 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. This aligns with a randomized controlled trial, which suggested that a higher intravenous magnesium dose (50 mg.kg−1 bolus + 30 mg.kg−1.h−1 infusion compared to 30 mg.kg−1 + 15 mg.kg−1.h−1) not only decreased postoperative pain scores but also effectively mitigated pneumoperitoneum-related hemodynamic instability during gastrointestinal laparoscopy.4545 Tan W, Qian D chen, Zheng M meng, Lu X, Han Y, Qi D yi. Effects of different doses of magnesium sulfate on pneumoperitoneum-related hemodynamic changes in patients undergoing gastrointestinal laparoscopy: a randomized, double-blind, controlled trial. BMC Anesthesiol. 2019;19:237. However, high-dose magnesium administration has been acknowledged to lead to more frequent bradycardia and hypotension likely.33 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. Most trials in our review employed a 40-50 mg.kg−1 bolus dose of magnesium.1313 Tauzin-Fin P, Sesay M, Delort-Laval S, Krol-Houdek MC, Maurette P. Intravenous magnesium sulphate decreases postoperative tramadol requirement after radical prostatectomy. Eur J Anaesthesiol. 2006;23:1055-9.,1414 Taheri A, Haryalchi K, Mansour Ghanaie M, Habibi Arejan N. Effect of low-dose (single-dose) magnesium sulfate on postoperative analgesia in hysterectomy patients receiving balanced general anesthesia. Anesthesiol Res Pract. 2015;2015.,1616 Singhvi B, Goyal G. Study the effect of a single dose of intravenous magnesium sulphate on postoperative pain after lower abdominal surgery. Inter J Med Res Professionals. 2020;57:57-62.

17 Shamim A, Salman W, Gul S. Effect of Magnesium Sulphate on postoperative pain in laparoscopic cholecystectomy. Int J Adv Res (Indore). 2015;3:813-8.

18 Seyhan TO, Tugrul M, Sungur MO, et al. Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery. Br J Anaesth. 2006;96:247-52.

19 Saadawy IM, Kaki AM, Abd El Latif AA, Abd-Elmaksoud AM, Tolba OM. Lidocaine vs. magnesium: Effect on analgesia after a laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2010;54:549-56.

20 Ryu JH, Koo BW, Kim BG, et al. Prospective, randomized and controlled trial on magnesium sulfate administration during laparoscopic gastrectomy: effects on surgical space conditions and recovery profiles. Surg Endosc. 2016;30:4976-84.

21 Rafiq W, Kumar Fotedar K, Wasim D, Resident RS. A Prospective randomized single Blinded controlled study to evaluate the effect of single dose of magnesium sulphate on Postoperative analgesia in abdominal Surgeries patients receiving balanced general anaesthesia. J Med Sci Clin Res. 2018;06:798-807.

22 Ryu JH, Kang MH, Park KS, Do SH. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth. 2008;100:397-403.

23 Park JY, Hong JH, Kim DH, Yu J, Hwang JH, Kim YK. Magnesium and bladder discomfort after transurethral resection of bladder tumor: A randomized, double-blind, placebo-controlled study. Anesthesiology. 2020;133:64-77.

24 Olgun B, Oǧuz GO, Kaya M, Şalvi S, Eskiçirak HE, Güney I, et al. The effects of magnesium sulphate on desflurane requirement, early recovery and postoperative analgesia in laparascopic cholecystectomy. Magnes Res. 2012;25:72-8.

25 Moon S, Lim S, Yun J, et al. Additional effect of magnesium sulfate and vitamin C in laparoscopic gynecologic surgery for postoperative pain management: a double-blind randomized controlled trial. Anesth Pain Med (Seoul). 2020;15:88-95.

26 Moharari RS, Motalebi M, Najafi A, et al. Magnesium can decrease postoperative physiological ileus and postoperative pain in major non laparoscopic gastrointestinal surgeries: A randomized controlled trial. Anesth Pain Med. 2014;4:e12750.
-2727 Mentes O, Harlak A, Yigit T, et al. Effect of intraoperative magnesium sulphate infusion on pain relief after laparoscopic cholecystectomy. Acta Anaesthesiol Scand. 2008;52:1353-9.,3030 Lee C, Jang MS, Song YK, et al. The effect of magnesium sulfate on postoperative pain in patients undergoing major abdominal surgery under remifentanil-based anesthesia. Korean J Anesthesiol. 2008;55:286.,3333 Kiran S, Gupta R, Verma D. Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery. Indian J Anaesth. 2011;55:31-5.,3434 Kim HY, Lee SY, Lee HS, Jun BK, Choi JB, Kim JE. Beneficial Effects of Intravenous Magnesium Administration During Robotic Radical Prostatectomy: A Randomized Controlled Trial. Adv Ther. 2021;38:1701-12.,3737 Bhatia A, Kashyap L, Pawar DK, Trikha A. Effect of intraoperative magnesium infusion on perioperative analgesia in open cholecystectomy. J Clin Anesth. 2004;16:262-5.

38 Ayoglu H, Karadeniz U, Kunduracilar Z, Ayoglu FN, Erdemli O. The analgesic effect of magnesium sulfate and ketamine in patients undergoing laparoscopic cholecystectomy. Pain Clinic. 2005;17:45-53.

39 Asadollah S, Vahdat M, Yazdkhasti P, Nikravan N. The effect of magnesium sulphate on postoperative analgesia requirements in gynecological surgeries. Turk Jinekoloji ve Obstetrik Dernegi Dergisi. 2015;12:34-7.
-4040 Arıkan M, Aslan B, Arıkan O, Horasanlı E, But A. Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study. Acta Cir Bras. 2016;31:67-73. Interestingly, two trials in our review utilized much lower magnesium doses, with Kocman et al. prescribing one group at 5 mg.kg−1 and another at 7.5 mg.kg−1 for laparoscopic cholecystectomy, and Dautaj et al. prescribing 3 mg.kg−1 for open cholecystectomy.3131 Kocman IB, Krobot R, Premuzić J, et al. The effect of preemptive intravenous low-dose magnesium sulfate on early postoperative pain after laparoscopic cholecystectomy. Acta Clin Croat. 2013;52:289-94.,3636 Dautaj B, Bulku E, Jaho E, et al. Effectivness of dexametasone vs. Magnesium sulphate in postoperative analgesia: Dexametasone vs. Magnesium sulphate. Serbian Journal of Anesthesia and Intensive Therapy. 2016;38:69-73. Even at lower doses, both trials found that the magnesium groups exhibited significantly better postoperative pain control with no difference in side effects compared to the control group.3131 Kocman IB, Krobot R, Premuzić J, et al. The effect of preemptive intravenous low-dose magnesium sulfate on early postoperative pain after laparoscopic cholecystectomy. Acta Clin Croat. 2013;52:289-94.,3636 Dautaj B, Bulku E, Jaho E, et al. Effectivness of dexametasone vs. Magnesium sulphate in postoperative analgesia: Dexametasone vs. Magnesium sulphate. Serbian Journal of Anesthesia and Intensive Therapy. 2016;38:69-73. Kocman et al. noted that a magnesium dose of 7.5 mg.kg−1 was more effective in preventing postoperative pain than the control and magnesium sulfate dose of 5 mg.kg−1.3131 Kocman IB, Krobot R, Premuzić J, et al. The effect of preemptive intravenous low-dose magnesium sulfate on early postoperative pain after laparoscopic cholecystectomy. Acta Clin Croat. 2013;52:289-94. A meta-analysis by De Oliveira et al. also demonstrated that systemic magnesium reduced postoperative pain and opioid consumption after various surgical procedures under GA, with a reduction in postoperative shivering also noted.4242 De Oliveira GS, Castro-Alves LJ, Khan JH, McCarthy RJ. Perioperative Systemic Magnesium to Minimize Postoperative Pain. Anesthesiology. 2013;119:178-90. Another systematic review by Guo et al. in 2015 confirmed that magnesium administration during GA decreased analgesic consumption and postoperative pain scores without increasing adverse events.4444 Guo BL, Lin Y, Hu W, et al. Effects of Systemic Magnesium on Post-operative Analgesia: Is the Current Evidence Strong Enough? Pain Physician. 2015;18:405-18. It is worth noting that Lysakowski et al. in 2007 did not agree with the effectiveness of perioperative magnesium on postoperative pain intensity and analgesic requirements.11 Lysakowski C, Dumont L, Czarnetzki C, Tramèr MR. Magnesium as an Adjuvant to Postoperative Analgesia: A Systematic Review of Randomized Trials. Anesth Analg. 2007;104:1532-9. De Oliveira et al. suggested that this discrepancy could be attributed to the fewer subjects in their observed studies, the inclusion of pediatric populations, and the allowance of various regional anesthesia methods. In contrast, our study was limited to adults and only included those undergoing GA to reduce clinical heterogeneity.4242 De Oliveira GS, Castro-Alves LJ, Khan JH, McCarthy RJ. Perioperative Systemic Magnesium to Minimize Postoperative Pain. Anesthesiology. 2013;119:178-90.

Kawakami et al. conducted a systematic review on magnesium and postoperative shivering, including 64 trials and 4303 patients. They also demonstrated that intravenous magnesium prevented postoperative shivering without resulting in increased adverse events.4646 Kawakami H, Nakajima D, Mihara T, Sato H, Goto T. Effectiveness of Magnesium in Preventing Shivering in Surgical Patients. Anesth Analg. 2019;129:689-700. The biological mechanism underlying this effect remains uncertain. Shivering can persist despite efforts to avoid hypothermia and may occur even in normothermic conditions. The resulting increase in oxygen demand, leading to heightened carbon dioxide production, may induce myocardial ischemia.4646 Kawakami H, Nakajima D, Mihara T, Sato H, Goto T. Effectiveness of Magnesium in Preventing Shivering in Surgical Patients. Anesth Analg. 2019;129:689-700. As magnesium exerts a calcium inhibitory effect, causing central arteriolar vasodilation and inducing the production of vasodilator prostaglandins, it possesses anticonvulsant properties and may slightly lower the shivering threshold in patients.4747 Wadhwa A, Sengupta P, Durrani J, et al. Magnesium sulphate only slightly reduces the shivering threshold in humans. Br J Anaesth. 2005;94:756-62.,4848 Dubé L, Granry JC. The therapeutic use of magnesium in anesthesiology, intensive care and emergency medicine: a review. Can J Anaesth. 2003;50:732-46.

Magnesium sulfate could be an effective adjunct for perioperative analgesia in adults undergoing GA for abdominal surgery. However, our results are constrained by the available evidence in published studies and may have happened by chance. We sought to minimize heterogeneity by restricting our inclusion criteria to general abdominal surgery procedures performed under GA. Despite these constraints, there might still be variability in expected pain severities and pain scores across the studies, even within general surgical procedures such as laparotomy versus laparoscopy. Heterogeneity could stem from differences in baseline chronic pain and opioid tolerance within the patient population, variations in specific surgical procedures, and diverse study designs across the included trials. The varied dosing and administration protocols for magnesium sulfate across studies limit the ability to draw definitive conclusions about the optimal regimen for analgesia in abdominal surgery. Future studies exploring the pharmacokinetics and pharmacodynamics of magnesium in more controlled temperature conditions to measure the impact on postoperative analgesia and shivering may offer valuable insights into its mechanism of action, aiding in identifying optimal dosing strategies for clinicians.

Conclusion

The findings of the present comprehensive analysis support magnesium sulphate's efficacy in providing perioperative analgesia for adults undergoing general abdominal surgery under general anesthesia. The observed reductions in postoperative pain scores, decreased opioid consumption, lower incidence of shivering, and prolonged time to rescue analgesia administration in the magnesium group highlight its potential as a valuable adjunct in pain management strategies. The results suggest incorporating magnesium sulfate into perioperative protocols may improve patient comfort and outcomes following surgery. Further research, including large-scale clinical trials, may be warranted to confirm these findings and elucidate the optimal dosing regimens and administration protocols for maximizing the analgesic benefits of magnesium sulfate in this context.

Declaration of competing interest

The authors declare no conflicts of interest.

Supplementary materials

Supplementary material associated with this article can be found in the online version at doi:10.1016/j.bjane.2024.844524.

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Publication Dates

  • Publication in this collection
    12 Aug 2024
  • Date of issue
    2024

History

  • Received
    18 Jan 2024
  • Accepted
    24 May 2024
  • Published
    06 June 2024
Sociedade Brasileira de Anestesiologia (SBA) Rua Professor Alfredo Gomes, 36, Botafogo , cep: 22251-080 - Rio de Janeiro - RJ / Brasil , tel: +55 (21) 97977-0024 - Rio de Janeiro - RJ - Brazil
E-mail: editor.bjan@sbahq.org