Trial of Skin Antisepsis in Surgery Could Double Antiseptics Recommended by WHO

Povidone iodine was found non-inferior to chlorhexidine gluconate in the largest randomized trial to compare the alcohol-based solutions for skin antisepsis in surgery.The findings support the CDC recommendation that either can be used, and should serve as impetus for the WHO to reconsider recommending only chlorhexidine gluconate.¹

In an editorial accompanying the study, JAMA associate editors Anthony Charles, MD, MPH, Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC, and Preeti Malani, MD, MS, Infectious Diseases and Geriatric Medicine, University of Michigan, Ann Arbor, MI, consider the implications for global surgery.²

"In addition to other evidence-based perioperative measures, the results of the study by Widmer et al provide more options for skin antisepsis, particularly in resource-limited settings given the large cost differential between povidone iodine and chlorhexidine gluconate in alcohol and the limited commercial availability of chlorhexidine gluconate-based antiseptics in some settings," Charles and Malani indicate.

Andreas Widmer, MD, MS, University Hospital Basel and University of Basel, Basel, Switzerland, and colleagues evaluated outcomes in over 3000 patients after cardiac or abdominal surgery with skin antisepsis from the different alcohol-based solutions, in a cluster-randomized, crossover non-inferiority trial at 3 tertiary care hospitals.

"Currently the preferred preparation remains controversial because choice of drug, exposure time, and number of applications likely influence the results of skin preparation," Widmer and colleagues observe.

"There has been a lack of standardization of these factors in previous trials, which did not compare compounds with similar alcohol-based formulations but also had relatively small sample sizes were single center, and/or were limited to specific surgical procedures," they pointed out.

To address these gaps in evaluating the antiseptics, the investigators randomly assigned each of the 3 sites to one month periods of use of either povidone iodine or chlorhexidine, over 18 consecutive months between September 2018 and March 2020. The sites utilized consistent formulations of the antiseptics, and maintainedstandardized processes of disinfectant application consistent with published protocols.

"Importantly, postdischarge patient follow-up was exceptionally good and ensured adequate identification of outcomes," the investigators noted. "The risk of confounding through contaminated operations, where proper skin preparation might be less relevant, was reduced by only including elective operations."

The primary outcome was surgical site infection within 30 days after abdominal surgery and within 1 year after cardiac surgery; with noninferiority margin of 2.5%. Secondary outcomes included surgical site infections, stratified by depth of infection and type of surgery. A total of 1598 patients received povidone iodine and 1762 chlorhexidine gluconate.

Widmer and colleagues report surgical site infections occurred in 80 (5.1%) of those in the povidone iodine group and in 97 (5.5%) of those receiving chlorhexidine gluconate; a difference of 0.4% (95% CI, -1.1%-2.0%).When corrected for clustering, the difference was well within the margin for noninferiority. The calculated unadjusted relative risk for povidone iodine vs chlorhexidine gluconate was 0.92 (0.69-1.23).There were no statistically significant differences between groups by type of surgical procedure.

Noting that the most recent WHO guidelines recommending only chlorhexidene-alcohol are based on low to moderate quality of evidence, Charles and Malani declare, "the current study by Widmer and colleagues provides evidence to the contrary and should prompt a change in the WHO guidance."

References

1.Widmer AF, Atkinson A, Kuster SP, et al. Povidone iodine vs chlorhexidine gluconate in alcohol for preoperative skin antisepsis. JAMA 2024;332(7):541-549.

2.Charles A, Malani PN. Skin antisepsis to prevent surgical site infections. Implications for global surgery. JAMA 2024;332(7):550.