Brazilian Journal of Anesthesiology
Brazilian Journal of Anesthesiology
Systematic Review

The effects of magnesium sulfate added to epidurally administered local anesthetic on postoperative pain: a systematic review

Os efeitos do sulfato de magnésio adicionado ao anestésico local administrado por via peridural na dor pós-operatória: uma revisão sistemática

Getúlio Rodrigues de Oliveira Filho, Adilto Mezzari Junior, Giulia Nonticuri Bianchi

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This study evaluated the efficacy of epidurally administered magnesium associated with local anesthetics on postoperative pain control.


The study protocol was registered in PROSPERO as CRD42021231910. Literature searches were conducted on Medline, Cochrane, EMBASE, CENTRAL, and Web of Science for randomized controlled trials comparing epidural administration of magnesium added to local anesthetics for postoperative pain in elective surgical adult patients. Primary outcomes were the time to the first Postoperative (PO) Analgesic Request (TFAR), 24-hour postoperative opioid consumption, and Visual Analog Scale (VAS) scores at the first six and 24 postoperative hours. Secondary outcomes included Postoperative Nausea and Vomiting (PONV), pruritus, and shivering. Quality of evidence was assessed using GRADE criteria.


Seventeen studies comparing epidural were included. Effect estimates are described as weighted Mean Differences (MD) and 95% Confidence Intervals (95% CI) for the main outcomes: TFAR (MD = 72.4 min; 95% CI = 10.22–134.58 min; p < 0.001; I2 = 99.8%; GRADE: very low); opioid consumption (MD = -7.2 mg (95% CI = -9.30 – -5.09; p < 0.001; I2 = 98%; GRADE: very low). VAS pain scores within the first six PO hours (VAS) (MD = -1.01 cm; 95% CI = -1.40–0.64 cm; p < 0.001; I2 = 88%; GRADE: very low), at 24 hours (MD = -0.56 cm; 95% CI = -1.14–0.01 cm; p = 0.05; I2 = 97%; GRADE: very low).


Magnesium sulfate delayed TFAR and decreased 24-hour opioid consumption and early postoperative pain intensity. However, imprecision and inconsistency pervaded meta-analyses, causing very low certainty of effect estimates.


Analgesia, epidural; Magnesium sulfate, therapeutic use; Pain, postoperative



Este estudo avaliou a eficácia do magnésio administrado por via peridural associado a anestésicos locais no controle da dor pós-operatória.


O protocolo do estudo foi registrado no PROSPERO como CRD42021231910. Pesquisas bibliográficas foram realizadas no Medline, Cochrane, EMBASE, CENTRAL e Web of Science para ensaios clínicos randomizados comparando a administração epidural de magnésio adicionado a anestésicos locais para dor pós-operatória em pacientes cirúrgicos eletivos adultos. Os desfechos primários foram o Tempo para a Primeira Solicitação de Analgésico Pós-operatório (PO) (TFAR), o consumo de opioides no pós-operatório de 24 horas e os escores da Escala Visual Analógica (VAS) nas primeiras seis e 24 horas de pós-operatório. Os desfechos secundários incluíram Náusea e Vômito Pós-operatório (NVPO), prurido e tremores. A qualidade da evidência foi avaliada usando critérios GRADE.


Dezessete estudos comparando peridural foram incluídos. As estimativas de efeito são descritas como diferenças médias ponderadas (MD) e intervalos de confiança de 95% (95% CI) para os principais resultados: TFAR (MD = 72,4 min; 95% CI = 10,22–134,58 min; p < 0,001; I2 = 99,8% ; GRAU: muito baixo); consumo de opioides (MD = -7,2 mg (95% CI = -9,30 - -5,09; p < 0,001; I2 = 98%; GRAU: muito baixo). Escores de dor VAS nas primeiras seis horas de PO (VAS) (MD = - 1,01 cm; IC 95% = -1,40–0,64 cm; p < 0,001; I2 = 88%; GRAU: muito baixo), em 24 horas (MD = -0,56 cm; IC 95% = -1,14–0,01 cm; p = 0,05; I2 = 97%; GRADE: muito baixo).


O sulfato de magnésio atrasou o TFAR e diminuiu o consumo de opioides em 24 horas e a intensidade da dor pós-operatória precoce. No entanto, a imprecisão e a inconsistência permearam as meta-análises, causando uma certeza muito baixa das estimativas de efeito.


Analgesia peridural; Uso terapêutico do sulfato de magnésio; Dor pós-operatória


1. Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 2017;10:2287−98.

2. Joshi GP, Ogunnaike BO. Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol Clin N Am. 2005;23:21−36.

3. Rawal N. Current issues in postoperative pain management. Eur J Anaesthesiol. 2016;33:160−71.

4. Popping DM, Elia N, Van Aken HK, et al. Impact of epidural anal- € gesia on mortality and morbidity after surgery: systematic review and meta-analysis of randomized controlled trials. Ann Surg. 2014;259:1056−67.

5. Wagemans MF, Scholten WK, Hollmann MW, et al. Epidural anesthesia is no longer the standard of care in abdominal surgery with ERAS. What are the alternatives? Minerva Anestesiol. 2020;86.

6. Li Y, Dong H, Tan S, et al. Effects of thoracic epidural anesthesia/analgesia on the stress response, pain relief, hospital stay, and treatment costs of patients with esophageal carcinoma undergoing thoracic surgery: A single-center, randomized controlled trial. Medicine (Baltimore). 2019;98:e14362.

7. Swain A, Nag DS, Sahu S, et al. Adjuvants to local anesthetics: Current understanding and future trends. World J Clin Cases. 2017;5:307.

8. McCartney CJL, Sinha A, Katz J. A qualitative systematic review of the role of n-methyl-d-aspartate receptor antagonists in preventive analgesia. Anesth Analg. 2004;98:1385−400.

9. 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.

10. Ng KT, Yap JLL, Izham IN, et al. The effect of intravenous magnesium on postoperative morphine consumption in noncardiac surgery: A systematic review and meta-analysis with trial sequential analysis. Eur J Anaesthesiol. 2020;37:212−23.

11. Choi GJ, Kim YI, Koo YH, et al. Perioperative magnesium for postoperative analgesia: an umbrella review of systematic reviews and updated meta-analysis of randomized controlled trials. J Pers Med. 2021;11:1273.

12. Morrison AP, Hunter JM, Halpern SH, et al. Effect of intrathecal magnesium in the presence or absence of local anaesthetic with and without lipophilic opioids: a systematic review and metaanalysis. Br J Anaesth. 2013;110:702−12.

13. Li L-Q, Fang M-D, Wang C, et al. Comparative evaluation of epidural bupivacaine alone and bupivacaine combined with magnesium sulfate in providing postoperative analgesia: a metaanalysis of randomized controlled trials. BMC Anesthesiol. 2020;20:39.

14. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA Statement. PLoS Med. 2009;6:e1000097.

15. U.S. National Institute of Health Research. PROSPERO. International prospective register of systematic reviews. https:// Accessed 12/23/2021.

16. Mitchell M, Muftakhidinov B, Winchen T, et al. Engauge digitizer software. Zenodo, 2020.

17. Gorlin AW, Rosenfeld DM, Maloney J, et al. Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids. J Pain Res. 2016;9:693−700.

18. Peng PWH, Sandler AN. A review of the use of fentanyl analgesia in the management of acute pain in adults. Anesthesiology. 1999;90:576−99.

19. Glass PS, Estok P, Ginsberg B, et al. Use of patient-controlled analgesia to compare the efficacy of epidural to intravenous fentanyl administration. Anesth Analg. 1992;74:345−51.

20. Ma J, Liu W, Hunter A, et al. Performing meta-analysis with incomplete statistical information in clinical trials. BMC Med Res Methodol. 2008;8:56.

21. Sterne JAC, Savovic J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019: l4898.

22. Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in metaanalysis. Biometrics. 2000;56:455−63.

23. Palmer TM, Sutton AJ, Peters JL, Moreno SG. Contour-enhanced funnel plots for metaanalysis. The Stata J. 2008;8:242−54.

24. Deeks JJ, Higgins JPT, Altman DG, Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, eds. Cochrane Handbook for Systematic Reviews of Interventions version 6.2, Cochrane; 2021. at org/handbook.

25. Harbord RM, Higgins JPT. Meta-Regression in Stata. Stata J. 2008;8:493−519.

26. Mustafa RA, Wiercioch W, Santesso N, et al. Decision-making about healthcare related tests and diagnostic strategies: user testing of GRADE evidence tables. PLOS ONE Edited by Mello RA de. 2015;10:e0134553.

27. Harbord RM, Harris RJ, Sterne JAC. Updated tests for smallstudy effects in meta-analyses. Stata J Promot Commun Stat Stata. 2009;9:197−210.

28. GRADEpro GDT [computer program]. Hamilton (ON): McMaster University; 2015.

29. Asha, V. A comparative study between epidural ropivacaine with magnesium sulphate and ropivacaine for lower limb surgeries 2012 at

30. Daabiss MA, Kandil A. Evaluation of the effect of magnesium vs. midazolam as adjunct to epidural bupivacaine in patients undergoing total knee replacement. BJMP. 2013;6:a610.

31. Elsharkawy RA, Farahat TE, Abdelhafez MS. Analgesic effect of adding magnesium sulfate to epidural levobupivacaine in patients with pre-eclampsia undergoing elective cesarean section. J Anaesthesiol Clin Pharmacol. 2018;34: 328−34.

32. Farouk S. Pre-incisional epidural magnesium provides pre-emptive and preventive analgesia in patients undergoing abdominal hysterectomy. Br J Anaesth. 2008;101:694−9.

33. Ghatak T, Chandra G, Malik A, et al. Evaluation of the effect of magnesium sulphate vs. clonidine as adjunct to epidural bupivacaine. Indian J Anaesth. 2010;54:308−13.

34. Gupta A, Goyal V, Gupta N, et al. A randomized controlled trial to evaluate the effect of addition of a single dose of epidural magnesium sulphate on the duration of postoperative analgesia in patients undergoing lower abdominal surgeries under epidural anaesthesia. Sri Lankan J Anaesthesiol. 2013;21:27−31.

35. Lakra AM, Shah P (Jain), Sundrani O, et al. Magnesium sulphate vs clonidine as an adjuvant to 0.5% bupivacaine in epidural anaesthesia for patients undergoing lower limb surgeries: a comparative study. J Evol Med Dent Sci. 2015;4:12680−90.

36. Lenin P, Elango P, Sivakumar G, et al. Comparison of epidural bupivacaine and bupivacaine-magnesium sulphate combination in lower abdominal surgeries. J Evol Med Dent Sci. 2017;6:4925−9.

37. Mohammad W, Mir SA, Mohammad K, et al. A randomized double-blind study to evaluate efficacy and safety of epidural magnesium sulfate and clonidine as adjuvants to bupivacaine for postthoracotomy pain relief. Anesth Essays Res. 2015;9:15−20.

38. Munshi B, Munshi A. Comparison of effects of magnesium sulphate v/s clonidine as an adjuvant to epidural bupivacaine in lower abdominal and lower limb surgeries. Natl J Med Res. 2016;6:284−7.

39. Omar H. Magnesium sulfate as a preemptive adjuvant to levobupivacaine for postoperative analgesia in lower abdominal and pelvic surgeries under epidural anesthesia (randomized controlled trial). Anesth Essays Res. 2018;12:256−61.

40. Rekha P. A Comparative study between epidural plain ropivacaine and ropivacaine with magnesium sulfate for elective lower limb surgeries. J Med Sci Clin Res. 2020. 08:262/72.

41. Roy S, Mrunalini M, Sowmya Sri A. A prospective, double blind randomized controlled study comparing the effects of magnesium sulphate versus clonidine as an adjunct to bupivicaine in sub umbilical surgeries. J Evol Med Dent Sci. 2015;4:9358−69.

42. Shahi V, Verma A, Agarwal A, et al. A comparative study of magnesium sulfate vs dexmedetomidine as an adjunct to epidural bupivacaine. J Anaesthesiol Clin Pharmacol. 2014; 30:538.

43. Radwan T, Awad M, Fahmy R, et al. Evaluation of analgesia by epidural magnesium sulphate versus fentanyl as adjuvant to levobupivacaine in geriatric spine surgeries. Randomized controlled study. Egypt J Anaesth. 2017;33:357−63.

44. Kandil AH, Hammad RAEA, Shafei MAE, et al. Preemptive use of epidural magnesium sulphate to reduce narcotic requirements in orthopedic surgery. Egypt J Anaesth. 2012;28:17−22.

45. Sun J, Wu X, Xu X, et al. A comparison of epidural magnesium and/or morphine with bupivacaine for postoperative analgesia after cesarean section. Int J Obstet Anesth. 2012;21:310−6.

46. Balshem H, Helfand M, Schunemann HJ, et al. GRADE guide- € lines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64:401−6.

47. Weir CJ, Butcher I, Assi V, et al. Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review. BMC Med Res Methodol. 2018;18:25.

48. Herroeder S, Schonherr ME, De Hert SG, et al. Magnesium € −essentials for anesthesiologists. Anesthesiology. 2011;114: 971−93.

49. Modolo NSP, de Barros GAM. Magnesium: the underestimated  ion. Braz J Anesthesiol. 2021;71:477−9.

50. Ozdogan L, Sastim H, Ornek D, et al. Neurotoxic effects of intrathecal magnesium sulphate. Braz J Anesthesiol. 2013; 63:139−43.

51. Gorczyca R, Filip R, Walczak E. Psychological aspects of pain. Ann Agric Environ Med AAEM. 2013: 23−7. Spec no. 1.

52. Hudcova J, McNicol E, Quah C, et al. Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database Syst Rev. 2006: CD003348.

53. Wooldridge S, Branney J. Congruence between nurses’ and patients’ assessment of postoperative pain: a literature review. Br J Nurs Mark Allen Publ. 2020;29:212−20.

54. Barbosa FT, Lira AB, Neto OB de Oliveira, et al. Tutorial for performing systematic review and meta-analysis with interventional anesthesia studies. Braz J Anesthesiol. 2019;69:299−306.

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