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Systematic Review and Cost Analysis Comparing Use of chlorhexidine with Use of Iodine for Preoperative Skin Antisepsis to Prevent Surgical Site Infection

  • Ingi Lee (a1) (a2), Rajender K. Agarwal (a3), Bruce Y. Lee (a4), Neil O. Fishman (a1) and Craig A. Umscheid (a5) (a2)...



To compare use of chlorhexidine with use of iodine for preoperative skin antisepsis with respect to effectiveness in preventing surgical site infections (SSIs) and cost.


We searched the Agency for Healthcare Research and Quality website, the Cochrane Library, Medline, and EMBASE up to January 2010 for eligible studies. Included studies were systematic reviews, meta-analyses, or randomized controlled trials (RCTs) comparing preoperative skin antisepsis with chlorhexidine and with iodine and assessing for the outcomes of SSI or positive skin culture result after application. One reviewer extracted data and assessed individual study quality, quality of evidence for each outcome, and publication bias. Meta-analyses were performed using a fixed-effects model. Using results from the meta-analysis and cost data from the Hospital of the University of Pennsylvania, we developed a decision analytic cost-benefit model to compare the economic value, from the hospital perspective, of antisepsis with iodine versus antisepsis with 2 preparations of chlorhexidine (ie, 4% chlorhexidine bottle and single-use applicators of a 2% chlorhexidine gluconate [CHG] and 70% isopropyl alcohol [IPA] solution), and also performed sensitivity analyses.


Nine RCTs with a total of 3,614 patients were included in the meta-analysis. Meta-analysis revealed that chlorhexidine antisepsis was associated with significantly fewer SSIs (adjusted risk ratio, 0.64 [95% confidence interval, [0.51–0.80]) and positive skin culture results (adjusted risk ratio, 0.44 [95% confidence interval, 0.35–0.56]) than was iodine antisepsis. In the cost-benefit model baseline scenario, switching from iodine to chlorhexidine resulted in a net cost savings of $16-$26 per surgical case and $349,904–$568,594 per year for the Hospital of the University of Pennsylvania. Sensitivity analyses showed that net cost savings persisted under most circumstances.


Preoperative skin antisepsis with chlorhexidine is more effective than preoperative skin antisepsis with iodine for preventing SSI and results in cost savings.


Corresponding author

Hospital of the University of Pennsylvania, Division of Infectious Diseases, 3400 Spruce Street, 3rd Floor, Silverstein Building, Suite E, Philadelphia, PA 19104, (


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