Povidone-iodine 1% is the most effective vaginal antiseptic for preventing post-cesarean endometritis: a systematic review and network meta-analysis

Background Direct comparison metaanalyses have reported benefits with presurgical vaginal preparation before cesarean delivery for the reduction of endometritis. These reports did not perform a multitreatment comparison of the various antiseptic solutions assessed in previous studies. Objective The purpose of this study was to review the literature systematically and quantitate and summarize indirectly the comparative efficacy of antiseptic formulations and their concentrations that are used for the preparation of the vagina before cesarean delivery in the prevention of endometritis and other infectious complications. Study Design We used MEDLINE, EMBASE (from their inception to November 2018) and Cochrane databases, biographies, and conference proceedings. We used randomized clinical trials of patients who underwent surgical preparation of the vagina with antiseptic formulations before cesarean delivery with the aim of reducing the risk of infectious morbidity. Our systematic review was registered and followed the Preferred Reporting Items for Systematic Review and Meta-analysis Extension for network meta-analysis guidelines. Network meta-analysis was performed with computerized software and used user-written programs to assess consistency, inconsistency, ranking probabilities, and graphing results. Direct and indirect pairwise comparisons of the various formulations and their concentrations were performed with the use of multivariate random-effects models and metaregression. A frequentist inference method was employed for the fitted model to estimate the ranking probabilities. Subgroup analyses for patients in labor, not in labor, and with ruptured membranes were conducted. Results For the prevention of endometritis, we identified 23 studies that comprised 7097 women who were allocated to the following treatments: povidone-iodine (1%, 5%, 10%), chlorhexidine (0.2%, 0.4%), metronidazole gel, cetrimide, or normal saline solution/no treatment. Direct and indirect pairwise comparisons indicated that, when compared with saline solution or no treatment, all antiseptic formulations decreased rates of endometritis (5.2% vs 9.1%; odds ratio, 0.48; 95% confidence interval, 0.35–0.65; 22 studies/6994 women). Individually, povidone-iodine (odds ratio, 0.43; 95% confidence interval, 0.28–0.64; 16 studies/5968 women), cetrimide (odds ratio, 0.34; 95% confidence interval, 0.13–0.90; 1 study/200 women), and metronidazole (odds ratio, 0.38; 95% confidence interval, 0.16–0.90; 1 study/224 women) significantly reduced the risk of endometritis. Rankings of vaginal preparations indicated that povidone-iodine 1% had the highest probability (72.7%) of being the most effective treatment for the prevention of endometritis. For the secondary outcomes of postoperative wound infection and fever, a significant reduction was found only with povidone-iodine (odds ratio, 0.61; 95% confidence interval, 0.48–0.78; 16 studies/5968 women; and odds ratio, 0.58; 95% confidence interval, 0.40–0.83; 12 studies/4667 women). Subgroup analyses also found that povidone-iodine significantly reduced risk of endometritis for women in labor (odds ratio, 0.42; 95% confidence interval, 0.20–0.88; 5 studies/1211 women), with ruptured membranes(odds ratio, 0.21; 95% confidence interval, 0.10–0.44; 4 studies/476 women), and undergoing planned cesarean delivery (odds ratio, 0.39; 95% confidence interval, 0.27–0.57; 8 studies/1825 women). Conclusion Among patients who underwent cesarean delivery, presurgical vaginal irrigation with povidone-iodine had the highest probability of reducing the risk of endometritis, postoperative wound infections, and fever.