BACKGROUND: Clinical trials regarding the antishivering effect of perioperative magnesium have produced inconsistent results. We conducted a systematic review and meta-analysis with Trial Sequential Analysis to evaluate the effect of perioperative magnesium on prevention of shivering. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and 2 registry sites for randomized clinical trials that compared the administration of magnesium to a placebo or no treatment in patients undergoing surgeries. The primary outcome of this meta-analysis was the incidence of shivering. The incidence of shivering was combined as a risk ratio with 95% CI using a random-effect model. The effect of the route of administration was evaluated in a subgroup analysis, and Trial Sequential Analysis with a risk of type 1 error of 5% and power of 90% was performed. The quality of each included trial was evaluated, and the quality of evidence was assessed using the Grading of Recommendation Assessment, Development, and Evaluation approach. We also assessed adverse events. RESULTS: Sixty-four trials and 4303 patients (2300 and 2003 patients in magnesium and control groups, respectively) were included. The overall incidence of shivering was 9.9% in the magnesium group and 23.0% in the control group (risk ratio, 0.42; 95% CI, 0.33–0.52). Subgroup analysis revealed that the incidence of shivering was lower with IV (risk ratio, 0.29; 95% CI, 0.29–0.54; Grading of Recommendation Assessment, Development, and Evaluation, moderate), epidural (risk ratio, 0.24; 95% CI, 0.13–0.43; Grading of Recommendation Assessment, Development, and Evaluation, low), and intrathecal administration (risk ratio, 0.64; 95% CI, 0.43–0.96; Grading of Recommendation Assessment, Development, and Evaluation, moderate). Only trials with low risk of bias were included for Trial Sequential Analysis. The Z-cumulative curve for IV magnesium crossed the Trial Sequential Analysis monitoring boundary for benefit even though only 34.9% of the target sample size had been reached. The Z-cumulative curve for epidural or intrathecal administration did not cross the Trial Sequential Analysis monitoring boundary for benefit. No increase in adverse events was reported. CONCLUSIONS: Perioperative IV administration of magnesium effectively reduced shivering and Trial Sequential Analysis suggested that no more trials are required to confirm that IV magnesium effectively reduces shivering. Accepted for publication December 12, 2018. Funding: This study was supported by funding from the Department of Anesthesiology, Yokohama City University, Yokohama, Japan. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://bit.ly/KegmMq). Trial registry number: CRD42018083337 (PROSPERO). URL: http://bit.ly/2Gu1mjl. Reprints will not be available from the authors. Address correspondence to Hiromasa Kawakami, MD, Department of Anesthesiology, Yokohama City University Medical Center, Urafunecho 4-57 Minamiku Yokohama, Kanagawa 232-0024, Japan. Address e-mail to hiro.k210@gmail.com. © 2019 International Anesthesia Research Society
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