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

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

doi:10.1016/j.bjane.2022.08.005

Getúlio Rodrigues de Oliveira Filho^** Corresponding author. E-mails:getulio.filho@ufsc.br, oliveirafilho.gr@gmail.com (G.R. de Oliveira Filho).

Universidade Federal de Santa Catarina, Departamento de Cirurgia, Florianópolis, SC, Brazil

https://orcid.org/0000-0001-6190-5653

Adilto Mezzari Junior

Universidade Federal de Santa Catarina, Departamento de Cirurgia, Florianópolis, SC, Brazil

https://orcid.org/0000-0002-8565-7110

Giulia Nonticuri Bianchi

Universidade Federal de Santa Catarina, Departamento de Cirurgia, Florianópolis, SC, Brazil

https://orcid.org/0000-0001-9521-7402

* Corresponding author. E-mails:getulio.filho@ufsc.br, oliveirafilho.gr@gmail.com (G.R. de Oliveira Filho).

Conflicts of interest

The authors declare no conflicts of interest.

Figures (6)
Tables (1)

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Figure 1
PRISMA study flow diagram.

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Figure 2
Forest plots of pooled comparisons of time to the first postoperative opioid request. Boxes represent the weighted mean difference between groups that received epidural magnesium sulfate (Magnesium) or 0.9% saline (Placebo). Black lines surrounding boxes represent the respective 95% Confidence Intervals (95% CI). The black diamond represents the pooled effect size, its middle point being the pooled averaged mean difference and the lateral extremes, the 95% confidence limits of the mean difference. IV, Inverse Variance Method; Random, Random-effects model; SD, Standard Deviation.

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Figure 3
Forest plots of pooled comparisons of postoperative opioid consumption. Boxes represent the weighted mean difference between groups that received epidural magnesium sulfate (Magnesium) or 0.9% saline (Placebo). Black lines surrounding boxes represent the respective 95% Confidence Intervals (95% CI). The black diamond represents the pooled effect size, its middle point being the pooled averaged mean difference and the lateral extremes, the 95% confidence limits of the mean difference. IV, Inverse Variance method; Random, Random-effects model; SD, Standard Deviation.

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Figure 4
Forest plots of pooled comparisons of VAS pain scores within the first 6 and 24 postoperative hours. Boxes represent the weighted mean difference between groups that received epidural magnesium sulfate (Magnesium) or 0.9% saline (Placebo). Black lines surrounding boxes represent the respective 95% Confidence Intervals (95% CI). The black diamond represents the pooled effect size, its middle point being the pooled averaged mean difference and the lateral extremes, the 95% confidence limits of the mean difference. IV, Inverse Variance method; Random, Random-effects model; SD, Standard Deviation.

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Figure 5
Forest plots of pooled comparisons of postoperative side-effects: PONV, pruritus, and shivering. Boxes represent the Risk Ratio (RR) between groups that received epidural magnesium sulfate (Magnesium) or 0.9% saline (Placebo). Black lines surrounding boxes represent the respective 95% Confidence Intervals (95% CI). The black diamond represents the pooled effect size, its middle point being the pooled risk ratio and the lateral extremes, the 95% confidence limits of the mean difference. IV, inverse variance method; Random, Random-effects model; SD, standard deviation.

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Figure 6
Rob 2 traffic-light plot showing results of within-studies risk of bias assessment. Although some concerns were raised on multiple aspects of most studies, no study showed reasons for assigning a high risk of bias in any domain of the RoB 2 tool.

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Table 1
Characteristics of the studies.

Study ID	n _MgSO4	n control	Control group	Administration of MgSO₄	Language	Surgery	Type of anesthesia	Epidural local anesthetic (LA)	Dose (LA)	Epidural MgSO₄ Bolus	Epidural MgSO₄ infusion	Duration of infusion	Rescue analgesics	Outcomes of interest
Asha 2012²⁹29 Asha, V. A comparative study between epidural ropivacaine with magnesium sulphate and ropivacaine for lower limb surgeries 2012 at http://repository-tnmgrmu.ac.in/7345/. http://repository-tnmgrmu.ac.in/7345/...	30	30	Placebo (0.9% saline)	Bolus	English	Lower limb surgeries	Epidural	Ropivacaine	16 mL 0.75%	50 mg		Before surgery	Epidural 9 mL of 0.25% ropivacaine bolus	TFAR, adverse effects
Daabis 2013³⁰30 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.	40	40	Placebo (0.9% saline)	Bolus + infusion	English	Knee replacement	Epidural	Bupivacaine	1 mL 0.5% per segment	50 mg	MgSO₄: 10 mg.h⁻¹	During the surgery	Epidural fentanyl 2 µg.mL⁻¹+ LA 0.08% bolus	Analgesic consumption (24 PO hours), VAS pain scores, PO adverse effects,
Elsharkawy 2018³¹31 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.	30	30	Placebo (0.9% saline)	Bolus	English	Cesarean section	Epidural	Levobupivacaine	20 mL 0.5%	500 mg		Before surgery	diclofenac 75 mg VO or fentanyl 0.5 1 µg.kg⁻¹ IV bolus	TFAR, analgesic consumption (24 PO hours), VAS pain scores, PO adverse effects
Farouk 2008a³²32 Farouk S. Pre-incisional epidural magnesium provides pre-emptive and preventive analgesia in patients undergoing abdominal hysterectomy. Br J Anaesth. 2008;101:694-9.	29	29	Placebo (0.9% saline infusion before anesthesia induction until the end of the surgery)	Bolus before induction of anesthesia + intraoperative infusion	English	Hysterectomy	General	Bupivacaine	None	50 mg	10 mg.h⁻¹	During surgery	Epidural lidocaine bolus on demand	Analgesic consumption (24 PO hours), VAS pain scores, PO adverse effects
Farouk 2008b³²32 Farouk S. Pre-incisional epidural magnesium provides pre-emptive and preventive analgesia in patients undergoing abdominal hysterectomy. Br J Anaesth. 2008;101:694-9.	29	29	Placebo (0.9% saline infusion before anesthesia induction until the end of the surgery)	Bolus at the end of the surgery + infusion	English	Hysterectomy	General	Bupivacaine	None	50 mg		During surgery	Epidural lidocaine bolus on demand	Analgesic consumption (24 PO hours), VAS pain scores, PO adverse effects
Ghatak 2010³³33 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.	30	30	Placebo (0.9% saline)	Bolus	English	Lower abdominal and lower limb surgeries	Epidural	Bupivacaine	19 mL 0.5%	50 mg		Before surgery	Epidural bupivacaine 0.25% 8 mL bolus	TFAR, analgesic consumption (24 PO hours), VAS pain scores, PO adverse effects
Gupta 2013³⁴34 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.	30	30	Placebo (0.9% saline)	Bolus	English	Hysterectomy	Epidural	Bupivacaine	9 mL 0.125%	50 mg		End of surgery	Epidural fentanyl 1 µg.kg⁻¹ bolus	TFAR, 24h analgesic consumption (24 PO hours), VAS pain scores, PO adverse effects
Kandil 2012⁴⁴44 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.	30	30	Placebo (0.9% saline)	Bolus	English	Lower limb surgery	Epidural	Bupivacaine	0.5% 1 mL per segment	50 mg	10 mg.h⁻¹	During surgery	PCEA fentanyl + LA+ pethidine IM	24h analgesic consumption (24 PO hours), VAS pain scores, PO adverse effects
Lakra 2015³⁵35 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.	30	30	Placebo (0.9% saline)	Bolus	English	Lower limb surgeries	Epidural	Bupivacaine	19 mL 0.5%	50 mg		Before surgery		PO adverse effects
Lenin 2012³⁶36 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 Sci2017;6:4925-9.	25	25	Placebo (0.9% saline)	Bolus	English	Lower abdominal surgeries	Epidural	Bupivacaine	19 mL 0.5%	50 mg		Before surgery		TFAR
Mohamad 2015³⁷37 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.	20	20	Placebo (0.9% saline)	Bolus	English	Thoracotomy	Epidural + general	Bupivacaine	8 mL 0.25%	50 mg		End of surgery	i.v. tramadol 50 mg	TFAR, analgesic consumption (24 PO hours), VAS pain scores, PO adverse effects
Munshi 2016³⁸38 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.	30	30	Placebo (0.9% saline)	Bolus	English	Lower abdominal surgeries and lower limb surgeries	Epidural	Bupivacaine	19 mL 0.5%	50 mg		Before surgery	Epidural tramadol 50 mg bolus	TFAR, PO adverse effects
Omar 2018³⁹39 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.	50	50	Placebo (0.9% saline)	Bolus + epidural infusion levobupivacaine + magnesium infusion 5 mL.h⁻¹ until the end of the surgery	English	Lower abdominal and pelvic surgeries	Epidural + general	Levobupivacaine	14 mL 0.5%	50 mg	15 mg.h⁻¹	during surgery	i.v. pethidine 1 mg.kg⁻¹+ paracetamol 1g	TFAR, VAS pain scores, PO adverse effects
Radwan 2017⁴³43 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.	22	22	Placebo (0.9% saline)	Bolus + infusion	English	Spine surgeries	Epidural + general	Levo-bupivacaine	14 mL 0.5%	50 mg	10 mg.h⁻¹ (LA 0.125%+ MgSO₄ 2 mg.mL⁻¹. 5 mL.h⁻¹)	During surgery	Para-cetamol 1g i.v. / 50 mg pethidine i.v.	Analgesic consumption (24 PO hours, VAS pain scores, PO adverse effects
Rekha 2020⁴⁰40 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.	30	30	Placebo (0.9% saline)	Bolus	English	Lower limb surgeries	Epidural	Ropivacaine	16 mL 0.75%	50 mg		Before surgery	Epidural ropivacaine bolus	TFAR, analgesic consumption (24 PO hours), PO adverse effects
Roy 2015⁴¹41 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.	30	30	Placebo (0.9% saline)	Bbolus	English	Infra-umbilical surgeries	Epidural	Bupivacaine	19 mL 0.5%	50 mg		Before surgery	Epidural bupivacaine 0.5% bolus	TFAR, VAS pain scores, PO adverse effects
Shahi 2014⁴²42 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.	40	40	Placebo (0.9% saline)	Bolus	English	Lower limb surgeries	Epidural	Bupivacaine	14 mL 0.5%	50 mg		before surgery	Epidural bupivacaine 12 mL 0.125% bolus	TFAR, analgesic consumption (24 PO hours), VAS pain scores, PO adverse effects
Sun 2012 ⁴⁵45 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.	50	50	Placebo (0.9% saline)	Bolus	English	Cesarean section	CSEA	Bupivacaine	10 mL 0.1%	500 mg		During surgery	Epidural 8 mL LA 0.1% bolus + FTN 1 µg.mL⁻¹+ MgSO₄ 1 mg.mL⁻¹	TFAR, analgesic consumption (24 PO hours, VAS pain scores, PO adverse effects

[1] * Corresponding author. E-mails:getulio.filho@ufsc.br, oliveirafilho.gr@gmail.com (G.R. de Oliveira Filho).

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

Abstract

Background

Methods

Results

Conclusions