skin surgical preparation agents1

190 VOL. 11 NO. 4 2009 REVIEWS IN UROLOGY

TREATMENT REVIEW

Skin Preparation for the Prevention of Surgical Site Infection: Which Agent Is Best?Micah L. Hemani, MD, Herbert Lepor, MD

New York University School of Medicine, New York, NY

Procedural and surgical site infections create difficult and complex clinicalscenarios. A source for pathogens is often thought to be the skin surface,making skin preparation at the time of the procedure critical. The most common skin preparation agents used today include products containingiodophors or chlorhexidine gluconate. Agents are further classified bywhether they are aqueous-based or alcohol-based solutions. Traditional aqueous-based iodophors, such as povidone-iodine, are one of the few prod-ucts that can be safely used on mucous membrane surfaces. Alcohol-basedsolutions are quick, sustained, and durable, with broader spectrum antimicro-bial activity. These agents seem ideal for longer open surgeries with the potential for irrigation or surgical spillage, such as cystoprostatectomy, radical prostatectomy, and retroperitoneal lymph node dissection.[Rev Urol. 2009;11(4):190-195 doi: 10.3909/riu0467]

© 2009 MedReviews®, LLC

Key words: Skin pathogens • Procedural and surgical site infection • Skin preparation solutions

Surgical site infection (SSI) complicates an estimated 5% of all clean-contaminated operations performed annually in US hospitals and accountsfor the most common nosocomial infection in surgical patients.1 Patients

who develop SSI have longer and costlier hospitalizations and are more likely tospend time in an intensive care unit (ICU), are 5 times more likely to be readmitted,and are twice as likely to die.2

Recognizing this substantial morbidity and economic burden, in 1999 the Cen-ters for Disease Control (CDC) issued standardized guidelines for the prevention ofsurgical infections. These included making specific evidence-based recommenda-tions for modifying patient factors that may predispose to infection, for the useof antimicrobial prophylaxis, for optimizing sterility in the operating room, andfor the use of antiseptic agents for skin preparation.

The choice of which specific agent to use for skin preparation was not addresseddue to the diversity of sites and approaches in surgery, as well as the absence ofdata on SSI risk in well-controlled, operation-specific studies.1 Therefore, the

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Skin Preparation for the Prevention of SSI

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choice of agent should be based pri-marily on the surgeon’s knowledge ofthe product’s efficacy, cost, and easeof use. Urologic surgeons have the ad-ditional challenge of choosing the bestagent for the variety of proceduresthat they perform, including intraperi-toneal and extraperitoneal surgery;scrotal, perineal, and vaginal opera-tions; endoscopy; and percutaneousrenal surgery. Each of these operativesites has different endogenous flora,body contours, and skin types, all fac-tors that influence the risk of SSI and,therefore, the best type of antisepticskin agent to use. This article focuseson skin preparation for the preventionof SSI with an assessment of currently

available antiseptic products and theirapplication to urologic surgery.

HistoryThe first use of an antiseptic skinagent in surgery is credited to theEnglish surgeon Joseph Lister (1827-1912). Prior to the mid-19th century,limb amputation was associated withan alarming 50% postoperative mor-tality from sepsis. Following LouisPasteur’s discovery that tissue decaywas caused by microscopic organ-isms, Lister theorized that the spreadof these microbes through surgicalwounds was responsible for death inthe postoperative period. Lister begantreating wounds with carbolic acid

(phenol) in an effort to prevent tissuedecay and the resultant infectiouscomplications. As a result, the inci-dence of surgical sepsis fell dramati-cally, catalyzing the adoption ofmodern antiseptic techniques, includ-ing instrument sterilization, the use ofsurgical scrub and rubber gloves, andsterile patient preparation.3

Modern Surgical Skin PreparationThe most common skin preparationagents used today include productscontaining iodophors or chlorhexidinegluconate (CHG). Agents are furtherclassified by whether they are aqueousor alcohol-based solutions (Table 1).1

Table 1Characteristics of Antiseptic Solutions

Mechanism of AntimicrobialAntiseptic Action Coverage Onset Duration Application Examples

Aqueous-iodophor Free iodine � Excellent for gram � Intermediate 2 hours19 2-step scrub Betadine*protein, DNA bacteria, good for and paint Scrub Care†

damage gram �, fungi, virus, Mtb

Aqueous-CHG Disrupts Excellent for gram �, Intermediate 6 hours20 2-step scrub Hibiclens‡

membranes good for gram � and and dry,virus, fair for fungus, repeatpoor for Mtb

Alcohol-iodophor Denatures Improved gram �, Rapid 48 hours 1-step paint DuraPrepprotein, free Mtb activity (DuraPrep)11 Dry time, solution§

iodine � protein, 96 hours minimum of Prevail-FX†

DNA damage (Prevail-FX)21 3 min on hairless surface

Alcohol-CHG Denatures Improved gram �, Rapid 48 hours22,23 Dry site: ChloraPrep||

protein, disrupts Mtb, fungal activity 30-sec scrub membranes Moist site:

2-min scrub Dry time, mini-mum of 3 min onhairless surface

Mtb, Mycobacterium tuberculosis; CHG, chlorhexidine gluconate.*Betadine® is from Purdue Products, LP (Stamford, CT).†ScrubCare® and Prevail-FX® are from Cardinal Health (Dublin, OH).‡Hibiclens® is from Mölnlycke Health Care US LLC (Norcross, GA).§3M™ DuraPrep™ Surgical Solution (Iodine Povacrylex [0.7% available iodine] and Isopropyl Alcohol, 74% w/w) Patient Preoperative Skin Preparationis from 3M Health Care (St. Paul, MN).||ChloraPrep® is from CareFusion, Inc. (Leawood, KS).Based on data from Mangram AJ et al.1

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Aqueous-Based SolutionsAqueous-based iodophors such aspovidone-iodine (PVP-I) contain io-dine complexed with a solubilizingagent that allows for the release of freeiodine when in solution. Iodine acts inan antiseptic fashion by destroyingmicrobial proteins and DNA. Iodophor-containing products enjoy widespreaduse because of their broad-spectrumantimicrobial properties, efficacy, andsafety on nearly all skin surfaces inpatients regardless of age. In theaqueous form, most commerciallyavailable iodophors require a 2-stepapplication in a scrub-and-painttechnique, and their activity is lim-ited by the amount of time the agentis in contact with the skin.4 A secondproduct, aqueous-based chlorhexi-dine gluconate (CHG), works by dis-rupting bacterial cell membranes.CHG has more sustained antimicro-bial activity and is more resistant toneutralization by blood productsthan the iodophors. CHG is appliedin a similar manner to PVP-I, butshould not be used in the genital re-gion. This agent has gained popu-larity as a hand-scrubbing andshowering antiseptic prior to surgery,but also continues to be used as apatient skin preparation agent.5

Alcohol-Based SolutionsEthyl and isopropyl alcohol are 2 of themost effective antiseptic agents avail-able. When used alone, alcohol is fastand short acting, has broad-spectrumantimicrobial activity, and is relativelyinexpensive.1 Alcohol-based solutionsthat contain CHG or iodophors havesustained and durable antimicrobialactivity that lasts long after alcoholevaporation.6 Because alcohol dries onexposed skin within moments ofapplication, these can be applied witha 1-step preparation as opposed to ascrub-and-paint technique.

A limitation to the use of alcohol inthe operating room is its flammabilityon skin surfaces prior to evaporation.

There have been a few reports ofoperating room fires originatingfrom alcohol-based skin preparationresulting in significant injury topatients and staff.7 Flammability canbe avoided by allowing skin to com-pletely dry and avoiding preparationof areas with excessive body hairthat can delay alcohol vaporization.

Additionally, alcohol-based solu-tions should not be applied to mucousmembranes and therefore have lim-ited utility as antiseptic agents priorto transurethral or transvaginal

surgery. Nevertheless, combinationsolutions with alcohol and CHG oriodophors have gained popularityamong general, cardiac, and orthope-dic surgeons and may have additionalutility in certain urologic procedures.Recent studies suggest that theseproducts may have greater efficacy,easier application, improved durabil-ity, and a superior cost profile whencompared with traditional aqueous-based solutions.

One such product, 3M™ DuraPrep™Surgical Solution (Iodine Povacrylex[0.7% available iodine] and IsopropylAlcohol, 74% w/w) Patient Preopera-tive Skin Preparation (3M Health

Care, St. Paul, MN), is an antisepticskin solution that contains iodinepovacrylex and isopropyl alcohol. Itis applied in 1 step, has a dry time ofa minimum of 3 minutes on hairlessskin, leaves a water-insoluble filmon the skin surface that maintainsantimicrobial activity for up to 48hours, and resists wash-off by salineand blood products (Figure 1). Invitro studies have demonstratedthat DuraPrep solution is effectiveagainst a broad range of microorgan-isms, including those most commonly

encountered in genitourinary (GU)surgery, including gram-negativerods, Staphylococcus species, andEnterococcus, as well as multidrug-resistant organisms such as methicillin-resistant Staphylococcus aureus(MRSA), methicillin-resistant Staphy-lococcus epidermidis (MRSE), andvancomycin-resistant enterococci(VRE).8 Furthermore, DuraPrep solu-tion accomplishes a 6-fold bacteriallog reduction within 1 minute of con-tact with a greater percentage releaseof free iodine when compared withthe leading aqueous iodophors.8

Another potential advantage of thisproduct is its durability in the surgical

Skin Preparation for the Prevention of SSI continued


Combination solutions with alcohol and CHG or iodophors have gainedpopularity among general, cardiac, and orthopedic surgeons and may haveadditional utility in certain urologic procedures. Recent studies suggest thatthese products may have greater efficacy, easier application, improveddurability, and a superior cost profile when compared with traditionalaqueous-based solutions.

Figure 1. Application of DuraPrep™ SurgicalSolution (3M Health Care, St. Paul, MN).Adapted with permission from 3M HealthCare.

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environment. In a prospective, ran-domized surgical simulation study,DuraPrep solution demonstrated betterantimicrobial activity after saline soakwhen compared with the leading CHGalcohol-based solution (ChloraPrep®;CareFusion, Inc., Leawood, KS), sug-gesting that it is particularly suitablefor use in “wet” surgical environments(Figure 2).9 Another unique feature ofDuraPrep solution is that it enhancesadhesion between surgical drapes andthe prepared skin surface, theoreticallylimiting the spread of organisms ontothe surgical field. In a randomized,prospective study comparing drapeadhesion in patients undergoing totaljoint replacement, patients preparedwith DuraPrep solution had signifi-cantly less area of drape lift than thoseprepared with PVP-I, 1.5 cm2 versus9.9 cm2, respectively (P � .0001).10

This adhesive property may be partic-ularly advantageous for long, openprocedures with the potential for fluidspillage on the surgical field, such ascystoprostatectomy, radical prostatec-tomy, and retroperitoneal lymph nodedissection (RPLND).

Although there have been no stud-ies in the urologic literature address-

ing the effect of this product on SSI,clinical studies have been conductedin general, cardiac, and orthopedicsurgery, as well as in patients under-going anesthesia procedures. In aprospective, randomized study ofgeneral surgery patients undergoingoperations 3 hours or longer, the useof DuraPrep solution resulted in a 3-fold decrease in SSI when comparedwith tincture of iodine.11 Anotherstudy of 3209 general surgical proce-dures compared the use of 3 skinpreparations: a povidone-iodinescrub-paint combination (Betadine®,Purdue Products, LP, Stamford, CT)(with an isopropyl alcohol applicationbetween the steps), ChloraPrep, andDuraPrep solution.12 This study em-ployed a sequential implementationdesign, and each agent was used for a6-month period for all generalsurgery cases. PSSIs were tracked for30 days.

DuraPrep solution was associatedwith the lowest infection rate (3.9%,compared with 6.4% for Betadine and7.1% for ChloraPrep [P � .002]). Insubgroup analysis, no difference inoutcomes was seen between patientsprepared with Betadine/alcohol and

those prepared with DuraPrep solution,but patients in both these groups hadsignificantly lower PSSI rates com-pared with patients prepared withChloraPrep (4.8% vs 8.2% [P � .001]).

In the cardiac literature, a compar-ison of DuraPrep solution with theleading PVP-I in patients at high riskfor SSI undergoing open heartsurgery, 4 of 101 patients in theDuraPrep solution group developedwound infections compared with 14of 108 in the PVP-I group.13 Atanother center, the introduction ofDuraPrep solution in a cardiac surgeryservice was associated with a morethan 50% reduction in overall SSI,sternal wound infection, and repeatsurgical intervention for infection.14

In a study of patients undergoingepidural catheter placement on anobstetrics ward, DuraPrep solution wasprospectively compared with PVP-I.The DuraPrep solution group showeda significant decrease in the numberof positive skin cultures obtainedimmediately after disinfection andimmediately prior to catheter re-moval. In addition, bacteria was cul-tured from 2 epidural catheter tips inpatients treated with DuraPrep solu-tion compared with 13 positive cul-tures from catheter tips in the PVP-Igroup.15 This finding suggests thatDuraPrep solution may be particu-larly suitable for percutaneous renalaccess procedures where catheters arefrequently left in place postopera-tively, thus serving as a potentialentry point for infection.

Finally, a prospective clinical studyin the orthopedic literature suggeststhat alcohol-based solutions withiodophor or CHG may have improvedefficacy at reducing bacterial countsin “moist” surgical sites or bodyregions with increased endogenousbacterial colonization. One hundredtwenty-five patients undergoing footand ankle surgery were randomizedto receive preparation with 3M™DuraPrep™ Surgical Solution (Iodine

DuraPrepSolution

ChloraPrep®

4.5

4

3.5

3

2.5

2

1.5

1

0.5

0Control Rinse Soak

4.13

4.13

3.89

3.67

3.67

3.2

DuraPrep Solution ChloraPrep®

Figure 2. Bacterial log reduction after saline challenge. *P � .003 for soak condition. Reproduced with permissionfrom Stahl JB et al.9

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Povacrylex [0.7% available iodine]and Isopropyl Alcohol, 74% w/w)Patient Preoperative Skin Prepara-tion, ChloraPrep, or Techni-Care®Surgical Scrub (Care-Tech Laborato-ries, Inc., St. Louis, MO). The sitestreated with alcohol-based solutionshad on average a 50% reduction inpositive cultures compared withthose treated with traditional anti-septic agents. Overall, ChloraPrepperformed 2-fold better than Dura-Prep solution, but the findings of thisstudy have been criticized becauseno neutralization agent was usedprior to obtaining cultures from thesurface of the treated areas. BecauseChloraPrep is a non-film formingantiseptic, without the use of a neu-tralizer, it is likely that in this group,sampling contaminated with antisep-tic led to ongoing bacterial death andexaggerated efficacy. Additionally,no patients developed SSI in theDuraPrep solution group.16

These findings can be generalizedto other “moist” surgical sites, sug-gesting that alcohol-based solutionsmay be efficacious for use in groin,scrotal, or perineal urologic surgery,especially for implantation offoreign devices such as penile pros-theses or artificial urinary sphincters

where minimizing bacterial counts iscritical.

In addition to an analysis of effi-cacy, ease of use, cost, and user satis-faction are important considerationswhen choosing a skin preparationagent. In a prospective comparisonof alcohol-based iodophors withtraditional PVP-I preparation, thealcohol-based solutions had shorter

application and drying times. Takinginto consideration operating roomtime and product expenses, thealcohol-containing products hadlower overall costs.17 Other studieshave confirmed this finding, showingthat the use of DuraPrep solution haspotential savings of $78 per patient

(Table 2).18 Despite these advantages,operating room personnel preferredPVP-I scrub-and-paint to the alcoholpreparations, citing concern overflammability as the most importantoverall deciding factor. Familiaritywith PVP-I scrub-and-paint, however,may have introduced bias into the as-sessment of user satisfaction becausepersonnel had little to no experience

Skin Preparation for the Prevention of SSI continued


Table 2Comparison of Antiseptic Products

OR Durability Incidence of Surgical Site Infection Ease of Use

Antiseptic Soak Drape lift General General Cardiac Application Cost

Stahl et al9 Jacobson et al10 Pinheiro et al11 Swenson et al12 Segal and Armstrong et al17 Roberts et al18

N � 36 N � 171 N � 214 N � 3209* Anderson13 N � 25 N � 200P � .006 P � .0001 P � .05 P � .002 N � 209 P � .0001

P � .02

DuraPrep 3.7 bacterial 1.5 cm2 4.8% 3.9% 4% 82.8 sec $56.96solution† log reduction With drape

application

Tincture of — — 14.7% — — —iodine

Prevail‡ — — — — 42.2 sec —

ChloraPrep§ 3.2 bacterial — — 7.1% — — —log reduction

PVP-I — 9.9 cm2 — 6.4% 13% 228 sec $135.28

OR, operating room; PVP-I, povidone-iodine. *Number of procedures.†DuraPrep™ solution is from 3M Health Care (St. Paul, MN).‡Prevail-FX® is from Cardinal Health (Dublin, OH).§ChloraPrep® is from CareFusion, Inc. (Leawood, KS).Adapted with permission from Roberts AJ et al.18

Alcohol-based solutions may be efficacious for use in groin, scrotal, or per-ineal urologic surgery, especially for implantation of foreign devices such aspenile prostheses or artificial urinary sphincters where minimizing bacterialcounts is critical.

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with alcohol-based solutions prior tothe study.19 With safe use and properinstruction, alcohol-based antisepticsmay save valuable time and operatingroom resources.

ConclusionThe goal of preoperative skin prepa-ration is to reduce the incidence ofSSI in a safe, user-friendly, and cost-effective manner. Because urologistsperform a breadth of different opera-tions accessing numerous surgicalsites, a standard antiseptic agent isunlikely to be uniformly optimal.Traditional aqueous-based iodophorssuch as PVP-I are ideal for trans-vaginal and transurethral surgeryand are one of the few products thatcan be safely used on mucous mem-brane surfaces. Likewise, alcohol-based solutions such as DuraPrep so-lution are quick, sustained, anddurable with broader spectrum an-timicrobial activity. These seem idealfor longer open surgeries with thepotential for irrigation or surgicalspillage, for percutaneous procedureswith indwelling catheters, and forprosthesis implantation when mini-mizing skin colony counts is criticalto prevent hardware infection. Be-cause alcohol is flammable, whenusing these products care must betaken to allow adequate drying time

and to remove excessive hair fromthe prepared field that may delayalcohol vaporization.

Dr. Micah L. Hemani and Dr. HerbertLepor have been reimbursed by 3M Com-pany for their contributions.

References1. Mangram AJ, Horan TC, Pearson ML, et al.

Guideline for prevention of surgical site infec-tion, 1999. Hospital Infection Control PracticesAdvisory Committee. Infect Control HospEpidemiol. 1999;20:250-278; quiz 279-280.

2. Kirkland KB, Briggs JP, Trivette SL, et al. Theimpact of surgical-site infections in the 1990s:attributable mortality, excess length of hospital-ization, and extra costs. Infect Control HospEpidemiol. 1999;20:725-730.

3. Newsom BD. Surgical wound infections: ahistorical review. Int J Infect Control. 2008;4;1.

4. Digison MB. A review of antiseptic agents forpre-operative skin preparation. Plast Surg Nurs.2007;27:185-189; quiz 190-191.

5. Hibbard JS. Analyses comparing the antimicro-bial activity and safety of current antisepticagents: a review. J Infus Nurs. 2005;28:194-207.

6. Beck WX. After 2000 years, alcohol still excels.Infections in Surgery. 1985;Sept:640.

7. Weber SM, Hargunani CA, Wax MK. DuraPrepand the risk of fire during tracheostomy. HeadNeck. 2006;28:649-652.

8. Data on file. St. Paul, MN; 3M Health Care.9. Stahl JB, Morse D, Parks PJ. Resistance of

antimicrobial skin preparations to saline rinseusing a seeded bacteria model. Am J InfectControl. 2007;35:367-373.

10. Jacobson C, Osmon DR, Hanssen A, et al.Prevention of wound contamination usingDuraPrep Solution plus loban 2 drapes. ClinOrthop Relat Res. 2005;439:32-37.

11. Pinheiro SM, Couto BR, Pimenta JP, et al. Ef-fects of iodophor skin preparation in reducingsurgical site infection. Abstract presented at:

14th Annual Meeting of the Society for Healthcare Epidemiology of America; April 17-20, 2004; Philadelphia, PA. Abstract 329.

12. Swenson BR, Hedrick TL, Metzger R, et al. Effectsof preoperative skin preparation on postopera-tive wound infection rates: a prospective studyof 3 skin preparation protocols. Infect ControlHosp Epidemiol. 2009;30:964-971.

13. Segal CG, Anderson JJ. Preoperative skinpreparation of cardiac patients. AORN J. 2002;76:821-828.

14. Squier C, Miller T, DiLucia B, et al. Cardiac by-pass surgery: intervention to decrease surgicalsite infections. Abstract presented at: 4th Decen-nial International conference on Nosocomial andHealth Care-Associated Infections in conjunctionwith the 10th Annual Meeting of the Society forHealthcare Epidemiology of America; March 5-9,2009; Atlanta, GA.

15. Birnbach DJ, Meadows W, Stein DJ, et al. Com-parison of povidone iodine and DuraPrep, aniodophor-in-isopropyl alcohol solution, for skindisinfection prior to epidural catheter insertionin parturients. Anesthesiology. 2003;98:164-169.

16. Ostrander RV, Botte MJ, Brage ME. Efficacy of sur-gical preparation solutions in foot and anklesurgery. J Bone Joint Surg (Am). 2005;87:980-985.

17. Armstrong EP, Patrick KL, Erstad BL. Comparisonof preoperative skin preparation products. Phar-macotherapy. 2001;21:345-350.

18. Roberts AJ, Wilcox K, Devineni R, et al. Skinpreparations in CABG surgery: a prospectiverandomized trial. Comp Surg. 1995;14:741-748.

19. Khera SY, Kostyal DA, Deshmukh N. A compari-son of chlorhexidine and povidone-iodine skinpreparation for surgical operations. Curr Surg.1999;56:341-343.

20. Data on file. Norcross, GA: Mölnlycke HealthCare, Inc.

21. Data on file. Dublin, OH: Cardinal Health.22. Garcia R, Mulberry G, Brady A, Hibbard JS. Com-

parison of ChloraPrep and Betadine as preopera-tive skin preparation antiseptics. Poster presentedat: 40th Annual Meeting of the Infectious DiseaseSociety of America; October 25, 2002; Chicago, IL.

23. Data on file. San Diego, CA: CareFusion, Inc.

Main Points• Aqueous-based iodophors, such as povidone-iodine, contain iodine complexed with a solubilizing agent, allowing for the release

of free iodine when in a solution. Iodine acts in an antiseptic manner by destroying microbial proteins and DNA. Iodophor-containing products enjoy widespread use because of their broad-spectrum antimicrobial properties, efficacy, and safety on nearlyall skin surfaces regardless of the patient’s age.

• Ethyl and isopropyl alcohol are 2 of the most effective antiseptic agents available. When used alone, alcohol is fast and shortacting, has broad-spectrum antimicrobial activity, and is relatively inexpensive. Flammability can be avoided by allowing skinto completely dry and by avoiding preparation of areas with excessive body hair that can delay alcohol vaporization.

• Recent studies suggest that alcohol-based solutions may have greater efficacy, easier application, improved durability, and asuperior cost profile when compared with traditional aqueous-based solutions.

• DuraPrep solution, an antiseptic skin solution that contains iodine povacrylex in isopropyl alcohol, shows durability in the sur-gical/procedural environment and enhances adhesion between surgical drapes and the prepared skin surface, theoretically limit-ing the spread of organisms onto the surgical field.

• Alcohol-based solutions are quick, sustained, and durable, with broader spectrum antimicrobial activity. These agents seem idealfor longer open surgeries with the potential for irrigation or surgical spillage.

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skin surgical preparation agents1

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