Relative efficacy of prophylactic strategies for postthyroidectomy hypocalcemia: a systematic review and network meta-analysis

Background:Routine prophylaxis for at-risk patients may reduce the occurrence of postoperative hypocalcemia but is not widely adopted due to a lack of evidence on the efficacy of available prophylactic strategies. In this study, we compared the relative efficacy of prophylactic strategies for postthyroidectomy hypocalcemia with a systematic review and network meta-analysis. Methods:PubMed, Embase, and Cochrane Library were searched, covering the period from 1980 to May 2022, for randomized controlled trials (RCTs) comparing calcium, vitamin D-3, activated vitamin D-3, teriparatide, steroids, and magnesium with placebo or each other in patients receiving total or completion thyroidectomy. Involved RCTs reporting symptomatic or biochemical hypocalcemia. The primary outcome was symptomatic hypocalcemia, defined as circumoral tingling, and Chvostek and Trousseau signs. The secondary outcome was biochemical hypocalcemia. Risk of bias was assessed using the Cochrane risk of bias assessment tool for randomized trials. Pooled estimates were calculated using a random-effects inverse-variance weighting model. The network meta-analysis was performed under the frequentist framework. This meta-analysis was registered on the PROSPERO (International prospective register of systematic reviews) (CRD42022299982). Results:Twenty-seven RCTs comprising 3382 patients are included. Prophylactic strategies of teriparatide, oral calcium plus vitamin D-3, and oral calcium plus activated vitamin D-3 are superior to placebo in reducing symptomatic hypocalcemia. Teriparatide emerged as the most effective strategy for symptomatic hypocalcemia [relative risk (RR): 0.18; 95% CI: 0.03-0.98], followed by oral calcium plus activated vitamin D-3 (RR: 0.42; 95% CI: 0.25-0.73) and oral calcium plus vitamin D-3 (RR: 0.43; 95% CI: 0.26-0.71). Evidence on monotherapy with either oral calcium or vitamin D-3 in reducing symptomatic hypocalcemia is insufficient. Intravenous calcium and oral calcium are effective in reducing biochemical hypocalcemia. Conclusions:This network meta-analysis provides information on the relative efficacy of current prophylactic strategies for postthyroidectomy hypocalcemia. Teriparatide performed better than other interventions and would seem appropriate for deployment among high-risk populations.