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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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1.Bruce J, Russell EM, Mollison J, Krukowski ZH. The measurement and monitoring of surgical adverse events. Health Technol Assess 2001;5(22):1194.
2.Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group. N Engl f Med 1996;334(19):12091215.
3.Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol 1999;20(4):250278.
4.National Institute for Health and Clinical Excellence (NICE). Surgical site infection: draft full guideline 2006. Accessed October 1, 2010.
5.Leaper DJ, Orr C, Maung Z, White A. Inflammation and Infection: STEP 2000 Module II. Royal College of Surgeons of England. Blackwell Science; 2001.
6.AORN. Standards, Recommended Practices, and Guidelines. Denver; 2006.
7.National Association of Theatre Nurses (NATN). NATN standards and recommendations for safe perioperative practice. Harrogate: NATN; 2004.
8. 3M DuraPrep surgical solution (iodine povacrylex [0.7% available iodine] and isopropyl alcohol, 74% w/w) patient preoperative skin preparation. XbeJLRV63SXXBgl.
9.Darouiche RO, Wall MJ Jr, Itani KM, Otterson MF, Webb AL, Carrick MM, et al.Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl I Med 2010;362(1):1826.
10.Deeks JJ, Higgins J.P.T., Altman D.G. Analyzing data and undertaking meta-analyses. In: Higgins J, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. Oxford; 2008:501.
11.Egger M, Zellweger-Zahner T, Schneider M, Junker C, Lengeier C, Antes G. Language bias in randomised controlled trials published in English and German. Lancet 1997;350(9074):326329.
12.Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:10881101.
13.Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al.Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials 1996;17(1):112.
14.Chalmers TC, Smith H Jr, Blackburn B, Silverman B, Schroeder B, Reit-man D, et al.A method for assessing the quality of a randomized control trial. Control Clin Trials 1981;2(1):3149.
15.Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al.GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924926.
16.Umscheid CA, Mitchell MD, Doshi JA, Agarwal R, Williams K, Brennan PJ. Estimating the proportion of reasonably preventable healthcare associated infections and associated mortality and costs. In: Program and abstracts of the 19th Annual Scientific Meeting of the Soceity for Healthcare Epidemiology of America 2009.
17.Edwards PS, Lipp A, Holmes A. Preoperative skin antiseptics for preventing surgical wound infections after clean surgery. Cochrane Database Syst Rev 2004;(3):003949.
18.Berry AR, Watt B, Goldacre MJ, Thomson JW, McNair TJ. A comparison of the use of povidone-iodine and Chlorhexidine in the prophylaxis of postoperative wound infection. J Hosp Infect 1982;3(1):5563.
19.Paocharoen V, Mingmalairak C, Apisarnthanarak A. Comparison of surgical wound infection after preoperative skin preparation with 4% chlor hexidine [correction of chlohexidine] and povidone iodine: a prospective randomized trial. J Med Assoc Thai 2009;92(7):898902.
20.Saltzman MD, Nuber GW, Gryzlo SM, Marecek GS, Koh JL. Efficacy of surgical preparation solutions in shoulder surgery. J Bone Joint Surg Am 2009;91(8):19491953.
21.Veiga DF, Damasceno CA, Veiga-Filho J, Figueiras RG, Vieira RB, Florenzano FH, et al.Povidone iodine versus Chlorhexidine in skin antisepsis before elective plastic surgery procedures: a randomized controlled trial. Plast Reconstr Surg 2008;122(5):170e171e.
22.Culligan PJ, Kubik K, Murphy M, Blackwell L, Snyder J. A randomized trial that compared povidone iodine and Chlorhexidine as antiseptics for vaginal hysterectomy. Am J Obstet Gynecol 2005;192(2):422425.
23.Ostrander RV, Botte MJ, Brage ME. Efficacy of surgical preparation solutions in foot and ankle surgery. J Bone Joint Surg Am 2005;87(5):980985.
24.Bibbo C, Patel DV, Gehrmann RM, Lin SS. Chlorhexidine provides superior skin decontamination in foot and ankle surgery: a prospective randomized study. Clin Orthop 2005;438:204208.
25.Brown TR, Ehrlich CE, Stehman FB, Golichowski AM, Madura JA, Eitzen HE. A clinical evaluation of Chlorhexidine gluconate spray as compared with iodophor scrub for preoperative skin preparation. Surg Gynecol Obstet 1984;158(4):363366.
26.Chaiyakunapruk N, Veenstra DL, Lipsky BA, Saint S. Chlorhexidine compared with povidone-iodine solution for vascular catheter-site care: a meta-analysis. Ann Intern Med 2002;136(11):792801.
27.Zamora JL, Price MF, Chuang P, Gentry LO. Inhibition of povidone-iodine's bactericidal activity by common organic substances: an experimental study. Surgery 1985;98(1):2529.
28.Larson E, Bobo L. Effective hand degerming in the presence of blood. J Emerg Med 1992;10(1):711.
29.Ayliffe GA. Surgical scrub and skin disinfection. Infect Control 1984;5(1):2327.
30.Gregoire G, Derderian F, Le Lorier J. Selecting the language of the publications included in a meta-analysis: is there a Tower of Babel bias? J Clin Epidemiol 1995;48(1):159163.
31.Chalmers TC, Berrier J, Sacks HS, Levin H, Reitman D, Nagalingam R. Meta-analysis of clinical trials as a scientific discipline. II: Replicate variability and comparison of studies that agree and disagree. Stat Med 1987;6(7):733744.
32.Chalmers TC, Levin H, Sacks HS, Reitman D, Berrier J, Nagalingam R. Meta-analysis of clinical trials as a scientific discipline. I: Control of bias and comparison with large co-operative trials. Stat Med 1987;6(3):315328.
33.Pham B, Klassen TP, Lawson ML, Moher D. Language of publication restrictions in systematic reviews gave different results depending on whether the intervention was conventional or complementary. J Clin Epidemiol 2005;58(8):769776.
34.Moher D, Fortin P, ladad AR, Juni P, Klassen T, Le Lorier J, et al.Completeness of reporting of trials published in languages other than English: implications for conduct and reporting of systematic reviews. Lancet 1996;347(8998):363366.
35.Moher D, Pham B, Lawson ML, Klassen TP. The inclusion of reports of randomised trials published in languages other than English in systematic reviews. Health Technol Assess 2003;7(41):190.
36.Herwaldt LA, Cullen JJ, Scholz D, French P, Zimmerman MB, Pfaller MA, et al.A prospective study of outcomes, healthcare resource utilization, and costs associated with postoperative nosocomial infections. Infect Control Hosp Epidemiol 2006;27(12):12911298.
37.Dimick JB, Pronovost PJ, Cowan IA, Lipsett PA. Complications and costs after high-risk surgery: where should we focus quality improvement initiatives? J Am Coll Surg 2003;196(5):671678.
38.Kirkland KB, Briggs JP, Trivette SL, Wilkinson WE, Sexton DI. The impact of surgical-site infections in the 1990s: attributable mortality, excess length of hospitalization, and extra costs. Infect Control Hosp Epidemiol 1999;20(11):725730.
39.Perencevich EN, Sands KE, Cosgrove SE, Guadagnoli E, Meara E, Piatt R. Health and economic impact of surgical site infections diagnosed after hospital discharge. Emerg Infect Dis 2003;9(2):196203.
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Infection Control & Hospital Epidemiology
  • ISSN: 0899-823X
  • EISSN: 1559-6834
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