Perioperative Magnesium for Postoperative Analgesia: An Umbrella Review of Systematic Reviews and Updated Meta-Analysis of Randomized Controlled Trials
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Eligibility Criteria
2.3. Data Extraction
2.4. Assessment of the Confidence and Quality of Evidence
2.5. Updated Meta-Analysis
2.6. Statistical Analysis
3. Results
3.1. Description of Included Systematic Reviews
3.2. Summary of the Evidences
3.3. Confidence and Quality of Evidence
3.4. Results of Updated Meta-Analysis
3.5. Publication Bias
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patients Group | First Author (Year) | Search Period | Type of Anesthesia | Route of Magnesium Administration | Number of Included RCT | Number of Participant (Magnesium/Control) | Type of Surgery |
---|---|---|---|---|---|---|---|
Adult patients | Shi (2021) | October, 2020 | GA RA | IA | 11 | 677 (343/334) | Arthroscopic knee surgery |
Ma (2021) | February, 2020 | GA RA | IV, IT, ED, local | 8 | 880 (440/440) | Cesarean section | |
Wang (2020) | March, 2020 | RA | IT | 10 | 720 (360/360) | Surgery procedure | |
Li (2020) | October, 2019 | RA GA + RA | ED | 11 | 724 (362/362) | Surgical procedure | |
Ng (2020) | January, 2019 | GA RA | IV | 51 | 3311 | Non-cardiac surgery | |
Chen (2018) | June, 2018 | GA | IV | 4 | 263 (131/132) | Laparoscopic cholecystectomy | |
Wang (2017) | November, 2016 | RA | IT, ED | 9 | 827 | Cesarean section | |
Zeng (2016) | January, 2016 | GA | IA | 8 | 513 (242/271) | Arthroscopic surgery | |
Guo (2015) | September, 2014 | GA RA | IV | 27 | 1504 | Surgical procedure | |
De Oliveira (2013) | June, 2012 | GA | IV | 20 | 1257 (639/618) | Surgical procedure | |
Albrecht (2013) | January, 2012 | GA RA | IV | 25 | 1461 (731/730) | Surgical procedure | |
Pascual-Ramirez (2013) | December, 2011 | RA | IT | 12 | 817 (412/405) | Below-umbilicus procedure | |
Murphy (2013) | July, 2011 | GA RA | IV | 22 | 1177 (599/578) | Surgery procedure | |
Pediatric patients | Kawakami (2018) | November, 2017 | RA | ED | 6 | 371 (179/192) | Surgical procedure |
Xie (2017) | June, 2016 | GA | IV, local | 10 | 665 (333/332) | Tonsillectomy | |
Cho (2017) | January, 2017 | GA | IV, local | 10 | 655 (328/327) | Tonsillectomy |
First Author, Year | Outcome | Study N | Participant N (Mg/Control) | MD, SMD, ES (95%CI) | Heterogeneity | Quality of Evidence (GRADE) |
---|---|---|---|---|---|---|
Shi 2021 | At rest | |||||
2 h | 8 | 423 (212/211) | MD −0.74 (−0.84, −0.64) | I2 = 0%, p = 0.51 | Low | |
4 h | 6 | 303 (152/151) | MD −0.24 (−0.37, −0.11) | I2 = 0%, p = 0.51 | Moderate | |
12 h | 6 | 304 (152/152) | MD −0.53 (−0.64, −0.41) | I2 = 0%, p = 0.51 | High | |
24 h | 7 | 372 (186/186) | MD −0.33 (−0.42, −0.24) | I2 = 0%, p = 0.51 | High | |
At movement | ||||||
2 h | 7 | 279 (140/139) | MD −0.46 (−0.64, −0.27) | I2 = 0%, p = 0.51 | High | |
4 h | 6 | 299 (150/149) | MD −0.85 (−1.40, −0.30) | I2 = 0%, p = 0.51 | Moderate | |
12 h | 6 | 299 (150/149) | MD −0.83 (−1.17, −0.48) | I2 = 0%, p = 0.51 | Moderate | |
24 h | 7 | 339 (170/169) | MD −0.58 (−0.79, −0.36) | I2 = 0%, p = 0.51 | High | |
Ma 2021 | Highest VAS | 8 | 880 (440/440) | MD −0.74 (−1.03, −0.46) | I2 = 91.7%, p < 0.001 | Low |
Last VAS | 8 | 880 (440/440) | MD −0.47 (−0.71, −0.23) | I2 = 95.0%, p < 0.001 | ||
Ng 2020 | 24 h | 18 | 1232 | MD −0.3 (−0.69, 0.09) | I2 = 91% | Low |
Chen 2018 | 2 h | 2 | 143 (71/72) | MD −0.45 (−0.88, −0.02) | I2 = 38%, p = 0.20 | Low |
8 h | 2 | 143 (71/72) | MD −0.62 (−0.95, −0.28) | I2 = 0%, p = 0.69 | ||
24 h | 2 | 100 (50/50) | MD −0.38 (−0.79, 0.02) | I2 = 4%, p = 0.31 | ||
Wang 2017 | At rest | 3 | 325 (164/161) | ES −1.206 (−2.084, −0.329) | I2 = 92.409, p < 0.001 | Low |
At movement | 2 | 265 (134/131) | ES −1.435 (−2.631, −0.240) | I2 = 94.265, p < 0.001 | ||
Zeng 2016 | Mg vs. placebo | Low | ||||
24 or 48 h | 5 | 289 (145/144) | MD −0.41 (−0.78, −0.05) | I2 = 80%, p = 0.0006 | ||
Mg vs. bupi | ||||||
24 or 48 h | 3 | 154 (77/77) | MD 0.17 (−0.92, 1.26) | I2 = 88%, p = 0.0002 | ||
Mg + bupi vs. bupi | ||||||
18 or 24 h | 3 | 154 (77/77) | MD −0.41 (−0.87, 0.04) | I2 = 73%, p = 0.03 | ||
Guo 2015 | At rest | NR | NR | CE | ||
total | SMD −1.43 (−2.74, −0.12) | p < 0.01 | ||||
At movement | ||||||
24 h | SMD −0.05 (−0.43, 0.32) | NR | ||||
De Oliveira 2013 | At rest | Moderate | ||||
Early (0–4 h) | 18 | 1153(567/586) | MD −0.74 (−1.08, −0.48) | I2 = 87% | ||
Late (24 h) | 13 | 606 (302/304) | MD −0.36 (−0.63, −0.09) | I2 = 71% | ||
At movement | ||||||
Early (0–4 h) | 6 | 466 (224/242) | MD 0.52 (−1.15, 0.10) | I2 = 57% | ||
Late (24 h) | 5 | 285 (142/143) | MD −0.73 (−1.37, −0.1) | I2 = 72% | ||
Albrecht 2013 | At rest | Low | ||||
Early | 15 | 868 (433/435) | MD −6.9 (−9.6, −4.2) | I2 = 79%, p < 0.00001 | ||
24 h | 14 | 900 (434/466) | MD −4.2 (−6.3, −2.1) | I2 = 78%, p < 0.00001 | ||
At movement | ||||||
Early | 5 | 381 (190/191) | MD −6.5 (−10.0, −2.9) | I2 = 78%, p = 0.19 | ||
24 h | 5 | 225 (112/113) | MD −9.2 (−16.1, −2.3) | I2 = 86%, p < 0.00001 | ||
Murphy 2013 | 4–6 h | 16 | 956 (477/479) | MD −0.67 (−1.12, −0.23) | I2 = 96%, p < 0.00001 | Low |
20–24 h | 15 | 908 (458/458) | MD −0.25 (−0.62, 0.71) | I2 = 94%, p < 0.00001 |
First Author, Year | Study Number | Participants Number (Mg/Control) | MD, SMD, ES (95%CI) | Heterogeneity | Quality of Evidence (GRADE) |
---|---|---|---|---|---|
Shi 2021 | 8 | 449 (229/220) | MD −4.23 (−4.64, −3.82) | I2 = 27%, p = 0.21 | High |
Ma 2021 | 5 | 290 (145/145) | SMD −3.20 (−5.45, −0.95) | I2 = 97.6%, p < 0.001 | Very low |
Li 2020 | 5 | 300 (150/150) | SMD −2.65 (−4.23, −1.06) | I2 = 96%, p < 0.00001 | Very low |
Ng 2020 | 19 | 945 | MD −5.41 (−7.08, −3.74) | I2 = 92%, p < 0.001 | Low |
Chen 2018 | 2 | 143 (71/72) | SMD −0.40 (−0.73, −0.07) | I2 = 0%, p = 0.57 | Moderate |
Wang 2017 | 4 | 193/193 | ES −1.620 (−2.434, −0.806) | I2 = 83.166%, p < 0.001 | Low |
Guo 2015 | NR | NR | SMD −1.72 (−3.21, −0.23) | NR | CE |
De Oliveira 2013 | 16 | 921 (479/442) | MD −10.52 (−13.50, −7.54) | I2 = 88% | Low |
Albrecht 2013 | 19 | 1054 (527/527) | MD −7.6 (−9.5, −5.8) | I2 = 92%, p < 0.00001 | Low |
Murphy 2013 | 12 | 698 (349/349) | MD −7.40 (−9.40, −5.41) | I2 = 87%, p < 0.00001 | Low |
First Author, Year | Study Number | Participants Number (Mg/Control) | MD, SMD, RoM (95%CI) | Heterogeneity | Quality of Evidence (GRADE) |
---|---|---|---|---|---|
Shi 2021 | 11 | 613 (311/302) | MD, 329.99 (228.73,431.24) | I2 = 99%, p < 0.00001 | Low |
Ma 2021 | 8 | 880 (440/440) | SMD, −3.0. (−4.32, −1.74) | I2 = 96.3%, p < 0.001 | Low |
Li 2020 | 6 | 400 (200/200) | SMD, 4.96 (2.75, 7.17) | I2 = 98%, p < 0.00001 | Very low |
Ng 2020 | 11 | 824 | MD, 143 (103, 183) | I2 = 99%, p < 0.001 | Low |
Wang 2020 | 9 | 660 (330/330) | RoM, 1.23 (1.13, 1.33) | I2 = 96%, p < 0.00001 | Low |
Zeng 2016 | 4 (Mg vs. placebo) | 229 (115/114) | MD, 3.59 (0.26, 6.93) | I2 = 99%, p < 0.00001 | Low |
3 (Mg vs. bupi) | 154 (77/77) | MD, −0.82 (−5.83, 4.20) | I2 = 99%, p < 0.00001 | ||
3 (Mg + bupi vs. bupi) | 154 (77/77) | MD, 6.25 (5.22, 7.29) | I2 = 69%, p = 0.04 | ||
De Oliveira 2013 | 4 | 339 (161/178) | MD, 4.4 (−6.9, 15.9) | NR | CE |
Albrecht 2013 | 4 | 298 (149/149) | MD, 7.2 (−1.9, 16.2) | I2 = 90%, p < 0.00001 | Low |
Pascual-Ramirez 2013 | 10 | NR | MD, 85 SMD, 0.98 (0.51, 1.37) | I2 = 56%, p < 0.001 | Moderate |
First Author, Year | Outcome | Study N | Participant N (Mg/Control) | RR, SMD, MD (95%CI) | Heterogeneity | Quality of Evidence (GRADE) |
---|---|---|---|---|---|---|
Kawakami 2018 | Incidence of rescue analgesia | 4 | 247 (117/130) | RR 0.45 (0.24, 0.86) | I2 = 62.5%, p = 0.046 | Very low |
Cho 2017 | Pain score | |||||
15 min | 6 | 405 (203/202) | SMD −0.26 (−0.52, 0.00) | I2 = 40.36%, p = 0.1232 | Low | |
1 h | 9 | 615 (308/307) | SMD 0.05 (−0.70, 0.80) | I2 = 94.94%, p < 0.0001 | ||
24 h | 6 | 330 (165/165) | SMD −0.39 (−0.71, −0.07) | I2 = 50.56%, p = 0.0727 | ||
Xie 2017 | Pain score | |||||
(mCHEOPs) | Low | |||||
15 min | 2 | 160 (80/80) | MD 0.17 (−0.02, 0.35) | I2 = 0%, p = 0.77 | ||
1 h | 2 | 160 (80/80) | MD −0.59 (−3.11, 1.93) | I2 = 98%, p < 0.00001 | ||
Incidence of rescue analgesia | 5 | 305 (153/152) | RR 0.53 (0.31, 0.91) | I2 = 69%, p = 0.01 | Low |
Postoperative Pain Score | Quantitative Meta-Analysis (SMD; 95% CI; pchi2; I2) | Description of Trial Sequential Analysis (TSA) | |
---|---|---|---|
PACU | Rest (0 h) | 0.395; 0.178–0.612; <0.001; 85.9% | Pain at rest (0 h): TSA indicated that 98.7% (2487 of 2520 patients) of the RIS was accrued. The cumulative Z curve crossed both the conventional test boundary and the trial sequential monitoring boundary. |
Rest (0–1 h) | 0.459; 0.229–0.689; <0.001; 87.1% | ||
Movement (0 h) | 0.437; −0.113–0.988; <0.001; 88.3% | Pain at movement (0 h): The trial sequential monitoring boundary was ignored due to too little information use. The cumulative Z curve did not cross the conventional test boundary. | |
Movement (0–1 h) | 0.485; −0.275–1.245; <0.001; 89.5% | ||
Early phase | Rest (4 h) | 0.872; 0.638–1.106; <0.001; 91.2% | Pain at rest (4 h): TSA indicated that accrued number of patients (3830) exceed the RIS (2959). The cumulative Z curve crossed both the conventional test boundary and the trial sequential monitoring boundary. |
Rest (0–4 h) | 0.705; 0.494–0.916; <0.001; 87.7% | ||
Movement (4 h) | 0.942; 0.364–1.520; <0.001; 93.2% | Pain at movement (4 h): TSA indicated that 89.0% (832 of 934 patients) of the RIS was accrued. The cumulative Z curve crossed both the conventional test boundary and the trial sequential monitoring boundary. | |
Movement (0–4 h) | 1.059; 0.561–1.556; <0.001; 89.6% | ||
Late phase | Rest (24 h) | 0.470; 0.307–0.633; <0.001; 81.6% | Pain at rest (24 h): TSA indicated that accrued number of patients (3500) exceed the RIS (3115). The cumulative Z curve crossed both the conventional test boundary and the trial sequential monitoring boundary. |
Movement (24 h) | 0.679; 0.388–0.970; <0.001; 61.1% | Pain at movement (24 h): TSA indicated that only 60.8% (507 of 834 patients) of the RIS was accrued. The cumulative Z curve crossed both the conventional test boundary and the trial sequential monitoring boundary. |
Postoperative Outcomes | Quantitative Meta-Analysis (SMD or RR; 95% CI; pchi2; I2) | Description of Trial Sequential Analysis (TSA) | ||
---|---|---|---|---|
Pain score | PACU | 0 h | 0.811; 0.194–1.429; <0.001; 94.2% | Pain (0 h): TSA indicated that only 12.6% (853 of 6776 patients) of the RIS was accrued. The cumulative Z curve crossed the conventional test boundary but returned within the conventional boundary during TSA. |
0–1 h | 0.553; 0.065–1.040; <0.001; 90.7% | |||
Early phase | 4 h | 0.536; 0.064–1.008; <0.001; 82.4% | Pain (4 h): The trial sequential monitoring boundary was ignored due to too little information use. The cumulative Z curve crossed the conventional test boundary but did not cross the trial sequential monitoring boundary. | |
0–4 h | 0.452; −0.010–0.914; <0.001; 89.7% | |||
Late phase | 24 h | 0.342; −0.360–1.044; <0.001; 93.8% | Pain (24 h): The trial sequential monitoring boundary was ignored due to too little information use. The cumulative Z curve did not cross the conventional test boundary. | |
Time to first analgesic | −1.222; −2.345–0.098; <0.001; 92.4% | The trial sequential monitoring boundary was ignored due to too little information use. The cumulative Z curve crossed the conventional test boundary but did not cross the trial sequential monitoring boundary. | ||
Analgesic consumption | 1.144; 0.370–1.917; <0.001; 88.8% | TSA indicated that only 10.1% (292 of 2881 patients) of the RIS was accrued. The cumulative Z curve crossed the conventional test boundary but did not cross the trial sequential monitoring boundary. | ||
Incidence of rescue analgesic | 1.991 *; 1.385–2.862; 0.014; 58.2% | TSA indicated that only 80.8% (552 of 683 patients) of the RIS was accrued. The cumulative Z curve crossed both the conventional test boundary and the trial sequential monitoring boundary. |
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Choi, G.J.; Kim, Y.I.; Koo, Y.H.; Oh, H.-C.; Kang, H. 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. https://doi.org/10.3390/jpm11121273
Choi GJ, Kim YI, Koo YH, Oh H-C, Kang H. Perioperative Magnesium for Postoperative Analgesia: An Umbrella Review of Systematic Reviews and Updated Meta-Analysis of Randomized Controlled Trials. Journal of Personalized Medicine. 2021; 11(12):1273. https://doi.org/10.3390/jpm11121273
Chicago/Turabian StyleChoi, Geun Joo, Young Il Kim, Young Hyun Koo, Hyoung-Chul Oh, and Hyun Kang. 2021. "Perioperative Magnesium for Postoperative Analgesia: An Umbrella Review of Systematic Reviews and Updated Meta-Analysis of Randomized Controlled Trials" Journal of Personalized Medicine 11, no. 12: 1273. https://doi.org/10.3390/jpm11121273