A Review of Anti-Septic Agents for Pre-Operative Skin Preparation Mary Beth Digison, BSN, RN

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CE A Review of Anti-septic Agents for Pre-operative Skin Preparation Mary Beth Digison, BSN, RN

re-operative skin preparation of the surgical site using remains a reservoir of potential pathogens. The body’s Pappropriate anti-septic product is recognized by the Cen- first line of defense is the skin. Invasive procedures ters for Disease Control and Prevention Guideline for Pre- disrupt this defense mechanism, allowing the normal endogenous flora to be introduced to the sterile com- vention of Surgical Site Infection, 1999, as a strongly recom- partments of the body. mended intervention to prevent surgical site infection. This article reviews anti-septic surgical skin preparation products according to the Food and Drug Administration classifica- SIGNIFICANCE tions, efficacy, and safety. It also examines pertinent research regarding anti-septic products. This information provides the An estimated 27 million surgical procedures are per- peri-operative registered nurse with information to make formed each year. Of these, 500,000 result in SSIs appropriate decisions when choosing anti-septic skin prepa- that comprise at least one third of all nosocomial ration products for surgical patients. infections, and are the most common nosocomial infection in surgical patients. These infections are In the late 1860s, the concept of asepsis was intro- responsible for 77% of the deaths in nosocomially duced into the practice of surgery. The practice of infected surgical patients (Mangram et al., 1999). asepsis has revolutionized surgery from a pursuit Many studies show that SSIs increase length of hos- which frequently resulted in sepsis and death, to a pital stay and costs. Patients who acquire an SSI medical intervention, which improves the quality and double their length of hospital stay and risk of death longevity of life. Despite the radical effect of aseptic (Dellinger, 2005). Annual costs associated with technique on the practice of surgery, surgical site increased hospitalization due to SSIs are in excess of infections (SSIs) remain a significant preventable $1.5 billion (Seal & Paul-Cheadle, 2004). Despite adverse outcome (Mangram, Horan, Pearson, Silver, & many advances in infection control, SSIs remain a Jarvis, 1999). principal cause of morbidity and mortality (Mangram Sterilization of instruments, maintenance of a ster- et al., 1999). ile field, anti-biotic prophylaxis, and hand disinfection According to the Centers for Disease Control and have contributed to the reduction of SSIs. These prac- Prevention (CDC), endogenous skin bacteria tices combine to create an aseptic surgical environ- (Staphylococcus aureus and coagulase-negative ment. In the past, the focus of effectiveness of anti- staphylococci) cause 34% of all SSIs. Studies show septic products has been aimed at surgical hand that the risk of SSIs is significantly increased if a scrubs with little attention being paid to patient skin surgical site is contaminated with a count of more preparation. The patient’s own body, however, than 105 micro-organisms per gram of tissue. Reduc- tion in the number of these skin micro-organisms may decrease the risk of SSIs. One strategy to reduce the microbial colonization of skin is pre-operative Mary Beth Digison, BSN, RN, is a masters of nursing administration candidate, University of Texas at Arlington School of Nursing. skin preparation. The purpose of pre-operative skin Address correspondence to Mary Beth Digison, BSN, RN (e-mail: preparation is to decrease resident and transient [email protected]). micro-organisms to subpathogenic levels quickly

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and to prevent the rebound of growth of micro- a log2 reduction on dry sites (i.e., abdomen) and log3 organisms (AORN, 2006). Pre-operative anti-septic reduction on moist sites (i.e., inguinal). skin preparation products are formulated to remove The immediate action relates to how quickly the a broad spectrum of microbes quickly and to provide anti-septic agent reduces microbial levels. Persistence continuously a high level of anti-microbial action for is the ability of an anti-microbial agent to prevent or up to 6 hr after use (Paulson, 2003). inhibit microbial growth on the skin after the product use (Paulson, 2003) (Table 1). The selection of the most appropriate anti-septic CLASSIFICATION OF HEALTHCARE product is the most essential step in pre-operative skin ANTI-SEPTICS preparation. Although the efficacy, immediate action, and persistence of the product are crucial, they must In the past, many topical anti-microbials were mar- be balanced with need to avoid tissue injury. The safe- keted that may have been ineffective or unsafe. To ty of pre-operative skin preparation anti-septics are a ensure that products used by American consumers significant concern for the peri-operative registered are safe and provide action as claimed by manufac- nurse (RN). Many skin anti-septics contain ingredients turers, the Federal Drug Administration (FDA) Divi- that can cause a direct or indirect injury to the surgi- sion of Over-the-Counter Drugs regulates anti-septic cal patient. Direct injuries resulting from anti-septic and other products. According to the FDA, pre- agents include ophthalmic damage, ototoxicity, skin operative skin preparation agents fall under the irritations, and anaphylactic reactions. Indirectly, category of healthcare anti-septics and are defined injuries can occur when alcoholic skin preparations as safe, rapid action, persistent products that act on ignite, causing fire in the operating room. The RN a broad spectrum of microbes and significantly should have a strong knowledge regarding the efficacy decrease the numbers of microbes on intact skin. and characteristics of skin anti-septic agents for skin These products must meet the testing specifications preparation of the surgical patient (Table 2). established in the FDA 1994 Tentative Final Mono- graph (TFM) for Healthcare Antiseptic Drug Products. The TFM establishes a framework for DESCRIPTION OF SKIN PREPARATION evaluation of safety and effectiveness of anti-septic ANTI-SEPTIC AGENTS healthcare products. Anti-septic healthcare products are classified into three categories: safe and Chlorhexidene Gluconate effective and not misbranded (Category I); not safe Chlorhexidene gluconate (CHG) has immediate, and effective or misbranded (Category II); and safe- persistent, and residual anti-microbial properties. ty and effectiveness cannot be confirmed because of This product has a strong tendency to bind the lack of evidence (Category III). Anti-septic ingredi- tissue, which contributes to its extended anti- ents not listed in the TFM are considered new microbial action. Depending on the concentration, drugs, which require a New Drug Application before it exerts bacteriostatic and bactericidal effects on a being marketed (Paulson, 2003). broad range of gram-positive and gram-negative The FDA TFM has adopted methods proposed by bacteria. CHG has limited sporicidal activity the American Society for Testing and Materials to (Paulson, 2003). evaluate the efficacy of pre-operative skin anti-septics. Efficacy pertains to the ability of an anti-septic skin product to significantly reduce the number of Iodophor resident and transient micro-organisms on the skin. Povidine-iodine (PVI) is the most commonly used form It is expressed as a log reduction. The FDA requires of iodophor and the most widely used pre-operative

TABLE 1 Efficacy of Anti-septic Agents

Anti-septic product FDA category Broad spectrum Immediate action Persistence

Parachlorometaxylenol (Techni-Care-Care-Tech I (safety) Fair Intermediate Good Laboratories, Inc)III (efficacy) Povidine-iodine (ScrubCare-Cardinal Health) I Good Intermediate Minimal Chlorhexidene gluconate (Hibiclens-Molnlycke Health Care) New drug Fair to good Intermediate Very good Isopropyl alcohol/iodophor (Duraprep™-3M Healthcare New drug Good Rapid Very good Professionals) Chlorhexidene gluconate with alcohol (Chloraprep®-Medi-Flex) New drug Very good Rapid Very good Alcohol with zinc pyrithione (Actiprep-HealthPoint) IVery good Rapid Very good

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TABLE 2 Characteristics of Pre-operative Skin Preparation Products

Anti-septic product Application Contraindications Safety Products comments

Povidine-iodine 7% scrub/10% paint Two steps: Allergy to iodine Avoid pooling, may Safe for use on vaginal (ScrubCare-Cardinal Health)1. Use scrub solution cause skin irritation area, face and head, for 5 min mucous membranes, Blot with sterile towel lumber puncture 2. Wipe on paint solution, Children 2 months allow to dry Iodophor 0.7%/isopropyl alcohol Paint single uniform Allergy to iodine May cause serious Improves occlusive drape 74% (Duraprep™-3M Healthcare application injury to eyes, ears adhesion Professionals) if allowed to enter and remain 3-min dry time Children 2 months Flammable, allow to May be left on post-op for dry before draping continued bacterial kill Not for open wounds, OK for spinal tap or epidural head and neck, catheter mucous membrane Chlorhexidene gluconate Swab liberally to Not for use on face, Rare, serious allergic OK for superficial wound 4% (Hibiclens-Molnlycke surgical site 2 min head, meninges, reaction Health Care) genitals, deep open wounds Blot with sterile towel Sensitivity to ingredients Serious eye/ear damage Repeat procedure Children 2 months for 2 min Blot with sterile towel Chlorhexidene gluconate Dry site (i.e., abdomen Not for use on face, Flammable: Allow to Effective in presence of blood 2%/isopropyl alcohol 70% and arm): Back head, meninges, dry before draping or organic matter (Chloraprep®-Medi-Flex) and forth motion genitals, deep open with applicator for wounds 30 seconds Wet site (i.e., inguinal Allergy to CHG Avoid contact with and axilla): Back and eyes, ears, mucous forth motion with membrane applicator for 2 min No blot; allow to dry Children 2 months for 3 min Chloroxylenol 3% (Techni- Full strength Sensitivity to None Safe for mucous membranes, Care-Care-Tech ingredients face, around eyes, ears, Laboratories, Inc) vaginal prep Apply directly to Children 2 months surgical site Blot with sterile towel or air dry Alcohol 73%/zinc pyrithione One uniform, thin Sensitivity to Flammable: Allow to Nonirritating to skin (Actiprep-HealthPoint) application ingredients dry before draping Dry for 2 min Not for use on Avoid contact with Avoid pooling mucous eyes membrane Not for use nonintact skin

skin anti-septic. This product has an excellent imme- in the presence of blood, necrotic tissue, or purulence diate anti-microbial effect. PVI has good local tolera- (Paulson, 2003). bility: it is not irritating or painful to the skin. It is effective against gram-positive and gram-negative bac- Parachlorometaxylenol teria, fungi, and protozoa. With the appropriate length of exposure time and concentration, iodophors are One of the oldest anti-microbials, parachlorometaxylenol also effective against mycobacterium, spores of Bacil- (PCMX, also known as chloroxylenol) is relatively lus spp and Clostridium spp. PVI may be less effective safe for human use. It has fair to good anti-microbial

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efficacy. It is not widely used as a skin preparation study demonstrated that the addition of alcohol to agent because of its comparatively less effective PVI results in a more efficacious anti-septic agent. anti-microbial action (Paulson, 2003). Segal and Anderson (2002) found that SSI rate was lower in cardiac surgical patients who had skin Alcohol and Alcohol-Based Agents preparation with an iodophor/alcohol product versus PVI. The authors note that the combination of Alcohols are broad spectrum, fast-acting anti- iodophor and alcohol in a water-insoluble film pro- microbials. They are ineffective against bacterial vides anti-microbial effects for up to 12 hr after appli- spores but generally effective against fungal species cation and provide a bacteriostatic action under a and some viruses. Although alcoholic anti-septics dressing for up to 3 days. have excellent immediate anti-microbial action, Hibbard (2005) conducted clinical trials to deter- they have limited persistence and residual effects mine the best pre-operative skin preparation agent on (Paulson, 2003). the basis of three criteria: immediate, persistent, and Currently, many products incorporate alcohol cumulative action. He found that the combination of along with other anti-septic agents to address the lack CHG and alcohol was superior in all three criteria in of persistence of alcohol. The addition of other anti- comparison with four other anti-septics: 70% alcohol, septic agents such as iodophor or CHG to an alcohol- 2% CHG, and 4% CHG or PVI. based agent is necessary to extend its persistence. Ostrander, Botte, and Brage (2005) compared the Another strategy to improve persistence of alcohol is combination of CHG and alcohol, PVI and alcohol, to add a preservative such as zinc pyrithione (ZPT). and chloroxylenol alone on pre-operative skin disin- The addition of ZPT provides persistence to alcohol fection of the foot and ankle. They found that the com- that is absent if it is used alone. This combination of bination of CHG and alcohol was the most effective alcohol and ZPT demonstrates rapid reduction of res- agent for eliminating bacteria from the foot. ident and transient flora, which exceeds FDA require- Guthery, Seal, and Anderson (2005) compared a ments (Seal & Paul-Cheadle, 2004). skin anti-septic formulation of ZPT/alcohol with The combination of alcohol with CHG shows an iodine/CHG. They concluded that this product improvement in immediate anti-microbial properties exceeded the efficacy of both CHG and iodine. Seal that provide superior clinical efficacy as a skin anti- and Paul-Cheadle (2004) tested ZPT with alcohol in a septic agent. The CHG component of this combination “systems approach” to pre-operative skin prepara- results in persistent anti-microbial action (Paulson, tion, which included washing of the sites at 12 and 2003). 6 hr before the pre-operative skin preparation using Another anti-septic agent, which may benefit from either the ZPT with alcohol product or 10% PVI. The the addition of alcohol, is iodophor. The combination alcohol-based product demonstrated greater anti- of isopropyl alcohol and iodophor results in a product microbial efficacy than the iodine-based product at with immediate efficacy that requires less time for nearly every test point and continued beyond the application in comparison with typical iodophor wound closure. agents (Segal & Anderson, 2002). There are few studies that assess the effect of pre- operative skin disinfection on SSI rates. However, logic dictates that eliminating the microbes, which are REVIEW OF PRE-OPERATIVE SKIN implicated in most SSIs, will decrease infection rates. DISINFECTION RESEARCH The anti-septic products with the broad spectrum, immediate, and persistent anti-microbial properties A number of studies have examined the most effec- should be the product of choice for the pre-operative tive skin anti-septic agent for infection prevention in preparation of skin. As this review indicates, products central venous pressure (CVP) catheters. A meta- that combine alcohol with CHG, PVI, or ZPT may be analysis of vascular catheter site studies found CHG the most effective skin disinfectants. In products with- to be more effective in preventing catheter-related out any alcohol, CHG alone is the more effective and bloodstream infections than povidine-iodine persistent skin anti-septic than PVI. (Chaiyakunapruk et al., 2002). On the basis of these studies, the CDC has published guidelines specifically recommending 2% CHG as a skin preparation agent CONCLUSIONS before insertion of CVP catheters (CDC, 2002). Unfortunately, there is no definitive guideline for SSIs are a significant issue for healthcare providers. pre-operative skin anti-septic agents. According to the CDC (Mangram et al., 1999), tech- Although PVI is categorized by the FDA as a Cate- niques aimed at reduction of microbial contamination gory I (safe and effective) skin anti-septic, studies of the patient’s tissue are an important prevention have demonstrated greater immediate and persistent measure for SSIs. Effective pre-operative skin disin- anti-microbial action by other anti-septic agents. One fection provides an opportunity to reduce SSIs.

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Anti-septic agents for skin disinfection must be select- HealthPoint. Actiprep. Retrieved April 23, 2007, from http:// ed on the basis of efficacy and safety. This requires that www.healthpoint.com/divisions/surgical/prodActiprep.cfm peri-operative RNs have thorough knowledge of prod- Hibbard, J. S. (2005). Analyses comparing the antimicrobial uct characteristics and manufacturer’s instructions for activity of current antiseptic agents: A review. Journal of each anti-septic product. The informed RN is able to Infusion Nursing, 28(3), 194–207. 3M Healthcare Professionals. 3MTM DuraprepTM Surgical Solu- choose among the available anti-septics for the most tion Iodine Povacrylex [0.7% available iodine] and iso- appropriate skin disinfection product to protect each propyl alcohol, 74% w(w) patient preoperative skin prepa- patient from SSI. ration. Retrieved April 23, 2007, from http://proucts3. 3m.com/catalog/us/en001/healthcare/professional/node_ GSF83Z3YYXbe/root_GST1T4S9TCgv/vroot_F9G1189154 REFERENCES ge/gvel_JLRV63SXXBgl/theme_us_professional_3_0/ AORN. (2006). Standards, recommended practices, and guide- command_AbcPageHandler/output_html lines. Denver, CO: AORN Publications. Mangram, A. J., Horan, T. C., Pearson, M. L., Silver. L. C., & Cardinal Health. Prep and skin care. Retrieved April 23, Jarvis, W. J. (1999). Guideline for prevention of surgical site 2007, from http://www.cardinal.com/mps/brands/prepskin/ infection, 1999. Atlanta, GA: The Hospital Practices Advi- patientprep.asp sory Committee, Centers for Disease Control and Preven- Care-Tech Laboratories, Inc. Antiseptics, wound infections, tion, Public Health Service, U.S. Department of Health topical infections. Retrieved April 23, 2007, from http:// and Human Services. www. caretechlabs.com/cart/ctl-products-technicare.html Medi-Flex. Chloraprep®—The rapid-acting, persistent, and Centers for Disease Control and Prevention. (2002). Guide- superior preoperative skin preparation. Retrieved April 23, lines for the prevention of intravascular catheter-related 2007, from http://www.medi-flex.com/chloraprep_com/ infections. MMWR Morbidity and Mortality Weekly Report, index.html 51(RR10), 1–26. Molnlycke Health Care. Hibiclens. Retrieved April 23, 2007, Chaiyakunapruk, N., Veenstra, D. L., Lipsky, B. A., Saint, S. from http://www.molnlycke.com/item.asp?id23793&si (2002). Chlorhexidene Compared with Poridine-Iodine 182 Solution for Vascular Catheter-Site Care: A Meta-Analysis. Ostrander, R. V., Botte, M. J., & Brage, M. E. (2005). Efficacy Annuals of Internal Medicine 136(11), 192–801. of surgical preparation solutions in foot and ankle surgery. Dellinger, E. P. (2005). Increasing inspired oxygen to decrease Journal of Bone & Joint Surgery, American Volume, 87(5), surgical site infection. Journal of the American Medical 980–985. Association, 249(16), 2091–2092. Paulson, D. S. (2003). Introduction to topical antimicrobials Food and Drug Administration. (1994). Topical antimicrobials and their applications. Handbook of topical antimicrobials: drug products for over-the-counter human use: Tentative Industrial applications in consumer products and pharma- final monograph for healthcare antiseptic drug products— ceuticals. New York: Marcel Dekker Inc. Proposed rule. Federal Register, 59, 31441–31452. Seal, L. A., & Paul-Cheadle, D. (2004). A systems approach to Guthery, E., Seal, L. A., & Anderson, E. L. (2005). Zinc preoperative surgical patient skin preparation. American pyrithione in alcohol-based products for skin antisepsis: Journal of Infection Control, 32(2), 57–62. Persistence of antimicrobial effects. American Journal of Segal, C. G., & Anderson, J. J. (2002). Preoperative skin prepa- Infection Control, 33(1), 15–22. ration of cardiac patients. AORN Journal, 76(5), 821–828.

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