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Antiseptics have long and commonly been used on wounds to prevent or treat infection. However, citing cytotoxicity data, many authors have advised against their use on open wounds. This article discusses antiseptics and their use on open wounds, as well reviews relevant animal studies and clinical trials examining the effects of commonly used antiseptics, including iodine compounds (povidone iodine and cadexomer iodine), chlorhexidine, hydrogen peroxide, acetic acid, and silver compounds. This article examines their effects on wound healing and reepithelization and their efficacy on reducing bacterial number in wounds and incidence of wound infections. The authors found despite cytotoxicty data, most antiseptics have not been shown to clearly impede healing, especially newer formulations like cadexomer iodine (which speeds healing) and novel silver delivery systems. These compounds appear to be relatively safe and efficient in preventing infection in human wounds. Given this review, the role of antiseptics on wounds and their role in wound care management should be reconsidered.
Antiseptics are agents that destroy or inhibit the growth and development of microorganisms in or on living tissue. Unlike antibiotics that act selectively on a specific target, antiseptics have multiple targets and a broader spectrum of activity, which include bacteria, fungi, viruses, protozoa, and even prions. Several antiseptic categories exist, including alcohols (ethanol), anilides (triclocarban), biguanides (chlorhexidine), bisphenols (triclosan), chlorine compounds, iodine compounds, silver compounds, peroxygens, and quaternary ammonium compounds. The most commonly used products in clinical practice today include povidone iodine, chlorhexidine, alcohol, acetate, hydrogen peroxide, boric acid, silver nitrate, silver sulfadiazine, and sodium hypochlorite.
Antiseptic uses and indications vary. Several antiseptic agents mainly focus on cleansing intact skin and are used for prepping patients preoperatively and prior to intramuscular injections or venous punctures, pre- and postoperative scrubbing in the operating room, and hand washing by medical personnel. Some also contain detergents, which render them too harsh for use on nonintact skin. The usefulness of antiseptics on intact skin is well established and broadly accepted. However, the use of antiseptics as prophylactic anti-infective agents for open wounds, such as lacerations, abrasions, burns, and chronic ulcers, has been an area of intense controversy for several years.
Two official guidelines have been released recently concerning antiseptic use on wounds. Povidone iodine has been Food and Drug Administration (FDA)-approved for short-term treatment of superficial and acute wounds. The statement includes that povidone iodine has not been found to either promote or inhibit wound healing. On the other hand, guidelines for the treatment of pressure ulcers by the US Department of Health and Human Services strongly discourage the use of antiseptics and promote the use of normal saline for cleansing pressure ulcers.
In clinical practice, antiseptics are broadly used for both intact skin and wounds, although concerns are raised based upon their effect on human cells and wound healing. Opinions are conflicting. Some authors strongly disapprove the use of antiseptics in open wounds. On the other hand, others believe antiseptics have a role in wound care, and their use may favor wound healing clinically.
The main rationale for using antiseptics on open wounds is prevention and treatment of infection and, therefore, increased rate of the healing process. It is established that infections may delay healing, cause failure of healing, and even cause wound deterioration. Microbial pathogens delay wound healing through several different mechanisms, such as persistent production of inflammatory mediators, metabolic wastes, and toxins, and maintenance of the activated state of neutrophils, which produce cytolytic enzymes and free oxygen radicals. This prolonged inflammatory response contributes to host injury and delays healing. Moreover, bacteria compete with host cells for nutrients and oxygen necessary for wound healing. Wound infection can also lead to tissue hypoxia, render the granulation tissue hemorrhagic and fragile, reduce fibroblast number and collagen production, and damage reepithelization. Consequently, although creation of an optimal environment for the wound healing process is currently the primary objective of wound care, addressing infection still plays a critical role in wound management.
Despite the universal acceptance of the detrimental role of infection on wound healing, the exact significance of increased bacterial load on wounds is still an area of debate. All chronic wounds are colonized by bacteria population, and it is known colonized wounds can heal. However, in addition to clinical infection, it seems that bacterial number above a critical concentration can decrease the wound healing rate and may have deleterious effects on the wound healing process. The role of bacteria in the chronicity of nonhealing wounds is under investigation. Likely, a state of bacterial contamination that can produce subclinical tissue damage exists. This may be caused by shear number or by other properties of the bacterial process. Increased bacterial numbers in pressure ulcers have been implicated as significant participants of chronic ulceration. Several studies have demonstrated that bacterial number above 105 or 106 organisms per gram can cause local disease to skin or can delay wound healing. Quantification of bacteria within wounds is not the sole predictor of the risk of infection, since several individualized factors, such as presence of foreign material and concomitant diseases, can decrease the ability of the hosts to defend themselves. Moreover, the nature of the wound and the virulence of microbes involved are important. In addition to use of antiseptics to reduce bacterial load of a wound, several other approaches have been developed, including debridement, cleansing and pulsating jet lavage for removal of the devitalized tissue, and application of topical antibiotics.
Another argument for the use of antiseptics on wounds to prevent wound infection is that antiseptics may be preferable to topical antibiotics with regard to development of bacterial resistance. Antibiotic resistance of skin wound flora has emerged as a significant problem, and measures to prevent it should be taken. Generally, antiseptics aim at eliminating all pathogenic bacteria of the wound, while antibiotics are effective only to certain bacteria that are sensitive to them. Although resistance toward antiseptics has been reported, it is to a significantly lesser degree than reported with antibiotic usage. According to McDonnell, et al., some acquired mechanisms of resistance (especially to heavy metals) are clinically significant, but in most cases the results have been speculative. Moreover, development of resistance against povidone iodine, which is the most commonly used antiseptic today, does not exist. Payne, et al., state that the sensible use of antiseptics could help decrease the usage of antibiotics, preserving their advantage for clinically critical situations.
Antiseptics are also considered superior to topical antibiotics when their rates of causing contact sensitization are compared. Aminoglycosides, especially neomycin, have a much higher sensitization rate compared to povidone iodine. Moreover, patients allergic to one antibiotic may acquire cross-allergy to other antibiotics, as well. The sensitization rate to povidone iodine, the most commonly used antiseptic, has been found to be only 0.73 percent.
A main concern for clinicians prior to applying a topical agent on an open wound is safety. Agents that are cytotoxic or cause delay in wound healing are used with reservation. The strongest argument against the use of antiseptics on wounds is that antiseptics have been found, primarily using in-vitro models, to be cytotoxic to cells essential to the wound healing process, such as fibroblasts, keratinocytes, and leukocytes. However, this cytotoxicity appears to be concentration dependent, as several antiseptics in low concentrations are not cytotoxic, although they retain their antibacterial activity in vitro. Since the in-vitro results are not always predictive of what may happen in vivo, numerous studies have been conducted on animal and human models. The results of these studies are conflicting and will be presented later in the article.
A second reason against the use of antiseptics on open wounds, as first stated by Fleming in 1919, is that antiseptics are not as effective against bacteria that reside in wounds as they are against bacteria in vitro. The presence of exudate, serum, or blood seems to decrease their activity. However, in practice, several bacteriological studies have shown that antiseptics can decrease bacterial counts within wounds.
In order to draw conclusions regarding the appropriateness and usefulness of antiseptic use on wounds, the authors have chosen to review the results of animal and human studies of the most common antiseptics used currently.
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