Antiseptics are chemical agents applied to the skin to reduce the microbial count and reduce the risk of surgical site infections (SSIs). SSIs are defined as an infection occurring at the surgical site within 30 days before a procedure and represent one of the most common complications of dermatologic surgery. Use of antiseptics dates back to the mid-1800s when Ignaz Semmelweis noted a dramatic decrease in periportal sepsis events with appropriate handwashing techniques, later reaffirmed with Lister’s use of carbolic acid showing improved infection control and reduction in surgical morbidity. Commonly used antiseptic agents in dermatologic surgery include chlorhexidine, povidone-iodine, chloroxylenol, isopropyl alcohol, hexachlorophene, benzalkonium chloride, and hydrogen peroxide. They should be used for most, if not all, procedures that enter the dermis of the skin or deeper.[1]

Each antiseptic possesses a specific mechanism of action and spectrum of microbes targeted, but also a side-effect profile that should be carefully weighed by the surgeon before selection for the chosen procedure. Other factors to consider when selecting an optimal surgical scrub include the underlying health status of the patient, the expected extent of surgery, the anatomic location of the tumor, and the planned reconstruction. Particularly as it relates to the skin, the most common pathogens implicated in SSIs are Staphylococcus aureus, followed by other gram-positive bacteria including coagulase-negative Staphylococcus, Enterococcus, and group A Streptococci. Additional implicated bacteria are gram-negative rods, particularly Escherichia coli and Pseudomonas. Broad-spectrum antiseptics generally cover more pathogens and subsequently are some of the most popular in dermatologic surgery.

Chlorhexidine

Chlorhexidine is a positively charged bisbiguanide at physiologic pH that binds to the negatively charged cell walls of bacteria, leading to a disruption in microbial cell membranes and precipitation of cell contents. At low concentrations, it is bacteriostatic, but at higher concentrations, it is bactericidal. Chlorhexidine displays a wide range of coverage including gram-positive and gram-negative bacteria, fungi, enveloped viruses, and Mycobacterial tuberculosis. Advantages include its broad-spectrum, fast onset of action, and excellent sustained/residual activity after being wiped from the field via binding to the stratum corneum.

Povidone-Iodine

Povidone-iodine is a complex of povidone, hydrogen iodide, and elemental iodine. It is thought to act via iodination (a form of halogenation) to oxidize lipids of the cell membrane and form salts with microbial proteins. Povidone-iodine is a broad-coverage antiseptic with microbicidal activity against gram-positive and gram-negative bacteria (including spores and M. tuberculosis), fungi, viruses, and protozoa. Additionally, this antimicrobial acts rapidly after application to the skin, but unlike chlorhexidine, it has minimal residual activity.

Chloroxylenol

Chloroxylenol is a halophenol that is thought to act by microbial cell wall disruption and inactivation of cellular enzymes. It is likely bactericidal with broad coverage of gram-positive and gram-negative bacteria, but less activity against M. tuberculosis, fungi, and viruses. Chloroxylenol is fairly slow-acting and has a minimal residual effect; despite this, it has shown a similar incidence of SSIs as chlorhexidine in a recent study.

Isopropyl Alcohol

Isopropyl alcohol is hydrophilic alcohol that likely causes membrane damage and denatures proteins needed for microbial metabolism and growth. Isopropyl alcohol is typically mixed with water because the microbial activity is greatest as a 60% to 90% solution rather than in the pure form or lower concentrations. Generally, alcohol solutions are thought to have most of their activity against gram-positive bacteria (bactericidal) but may have minor activity against some viruses and fungi. While one of the weaker cleansing agents with minimal residual activity, it has the fastest onset of action of the antiseptics.

Hexachlorophene

Hexachlorophene is a bisphenol compound that primarily acts by inhibition of the membrane-bound portion of the electron transport chain but may also disrupt microbial cell membranes.  At concentrations used in skin-cleansing agents, it is bacteriostatic and is primarily only active against gram-positive cocci, with little activity against gram-negative organisms and no fungal coverage. Hexachlorophene has the advantage of having a residual activity for several hours after use and gradually reduces bacterial counts after multiple uses (cumulative effect). Newer agents with broader antimicrobial coverage and fewer side effects have largely replaced hexachlorophene as a surgical scrub.

Benzalkonium Chloride

Benzalkonium chloride is a quaternary ammonium detergent (also called a cationic surfactant) that acts by irreversibly binding to phospholipids and proteins of the membrane, disrupting the cell membrane. It acts as a bactericide against many gram-positive and gram-negative bacteria but has inconsistent coverage against fungi, viruses, and mycobacteria. The advantages of benzalkonium are its stability and ability to be applied with a low incidence of irritant contact dermatitis. Similar to hexachlorophene, benzalkonium has been replaced by antiseptics with better antimicrobial coverage.

Hydrogen Peroxide

Hydrogen peroxide is the simplest peroxide that forms highly reactive free radicals (hydroxyl radical) that attack and oxidize essential cell components including lipids, proteins, and nucleic acids. Although generally better against gram-positive bacteria, hydrogen peroxide also has a microbicidal effect on gram-negative bacteria, bacterial spores, fungi, and viruses at higher concentrations and with longer contact times. In addition to its broad spectrum, it has a rapid onset of action and low cost which made it an attractive option in the past. While a common at-home remedy, the evidence argues against routine use as a surgical scrub or cleansing agent due to known cytotoxicity to keratinocytes.[2][3][4][2]

All of the discussed antiseptics are administered topically onto the skin surface. However, the application may differ depending on the antiseptic, concentration, and/or formulation. The 2 most widely administered antiseptic surgical scrub agents in dermatologic surgery are chlorhexidine and povidone-iodine.

Chlorhexidine-based scrubs are generally composed of 0.5% to 4% chlorhexidine in alcohol or aqueous base typically combined with detergent. Recent evidence suggests that it provides a bactericidal activity for 24 hours after a 2-minute application, making it a useful antiseptic for anticipated long procedures. As chlorhexidine can cause irreversible keratitis and middle ear ototoxicity (with sensorineural deafness), topical administration is relatively contraindicated for skin preparation involving or adjacent to the eye and conchal bowl. Chloroxylenol 3% surgical scrub solution may be safely substituted and used for these areas.

Povidone-iodine scrubs are composed of 7.5% to 10.0% povidone-iodine, typically in an aqueous or alcohol base, and are occasionally combined with detergent. The scrub is painted on a clean skin surface and allowed to dry. The product must dry to be bactericidal with a preferred minimum of 2 minutes drying time, although the latter can vary depending on the product used as the scrub. Povidone-iodine aqueous scrubs can be safely used near the eye and conchal bowl.

Given the advantages of chlorhexidine and povidone-iodine, other antiseptics are either used less often or are primarily historical in dermatologic surgery. Briefly, isopropyl alcohol comes as a solution and is used most often as a swab to cleanse the skin before a biopsy. Hexachlorophene scrub is an emulsion, while benzalkonium and hydrogen peroxide are both solutions. All are primarily historical with regards to antisepsis in dermatologic surgery.[3][5][6]

While generally tolerated well, adverse effects of antiseptic agents should be carefully weighed before selection to avoid unwanted complications.

Chlorhexidine can cause permanent keratitis, conjunctivitis, and permanent sensorineural deafness (entrance to the middle ear via hole/tear of the tympanic membrane). Chronic use can cause irritant contact dermatitis, and it is reportedly a rare contact allergen.[3][7]

Povidone-iodine can stain the skin, hair, and clothing. Severe irritant contact dermatitis can be invoked when left on the skin for prolonged periods, and it is a known contact allergen that can cross-react with iodides in medications and radiopaque iodine. Microbicidal activity is lost when povidone-iodine comes into contact with blood or sputum. There are also reports of neonatal hypothyroidism with chronic maternal use via percutaneous absorption of the iodides causing a Wolff-Chaikoff effect in newborns.[8]

Isopropyl alcohol can induce irritant contact dermatitis and is flammable in the setting of electrocautery.

Hexachlorophene was largely removed from the market after it was linked to the deaths of multiple people via neurotoxicity and brain damage. Additionally, percutaneous absorption can also cause teratogenic effects in the fetuses of pregnant women. 

Benzalkonium chloride can cause ocular toxicity and allergic contact dermatitis. While generally considered less irritating to tissues, it has also been shown to cause irritant contact dermatitis with prolonged skin exposure. Anionic compounds such as soap rapidly inactivate benzalkonium chloride.[9][10]

Contact allergy to chloroxylenol is becoming increasingly recognized with increased prevalence as a product preservative, in addition to its known irritant effects.[11]

Hydrogen peroxide is cytotoxic to keratinocytes in culture and presumably can impede the reepithelialization of wounds. It has a bleaching action that can whiten skin, hair, nails, and clothes.