Topical Wound Medications.Pdf

Topical Wound Medications Britta S. Leise, DVM, PhD KEYWORDS Horse Wound healing Ointments Antiseptics Topical antimicrobials KEY POINTS Topical antiseptics used for wound cleansing should be diluted appropriately to maximize microbial killing and minimize cytotoxic effects to the wound bed. When possible, topical antimicrobial medications are recommended in place of systemic antibiotics in the management of equine wounds. Topical antimicrobials can be more effective, because many have the ability to work in the presence of a biofilm or have properties to help eliminate biofilms from the wound bed. Topical medications can be used to manipulate the healing process or enhance the wound environment to promote healing. For example, corticosteroids can be used when exces- sive granulation tissue is present. Other therapies, such as honey or platelet-rich plasma, have various properties that improve autolytic de´ bridement of wounds and provide factors that improve normal wound healing. LAVAGE SOLUTIONS Topical cleaning agents should provide antisepsis but should not be cytotoxic to the healthy tissue within a wound. Prior to antiseptic application, a wound should be pre- pared by applying a water-soluble sterile lubricant, followed by clipping of the wound margins to remove hair. Many equine wounds have substantial contamination with dirt and debris and may have been cleaned by a layperson prior to the arrival of the veteri- narian. In these cases, nonsterile tap water may have been used. Although irrigating wounds with tap water does not increase microbial colonization,1 the use of tap water is reported to be cytotoxic to skin fibroblasts.2 The cytotoxic effects of tap water are attributed to alkaline pH, hypotonicity, and presence of cytotoxic trace elements.2 Clin- ically, however, in humans the use of tap water to clean wound does not delay healing. The most common agent used by veterinarians to clean equine wounds is 0.9% sodium chloride. Saline provides its antiseptic effects via dilution when used as a lavage. Saline, however, does have mild cytotoxic effects in vitro on canine fibroblasts after 10 minutes of exposure. This results from the slightly acidic pH of normal saline and the lack of a buffering system. Lactated Ringer solution does not result in fibroblast damage2; therefore, the use of such isotonic solutions may be preferred over the use of 0.9% sodium chloride. Disclosure Statement: The author has nothing to disclose. Equine Surgery, Veterinary Clinical Sciences, Louisiana State University, School of Veterinary Medicine, Skip Bertman Drive, Baton Rouge, LA 70803, USA E-mail address: [email protected] Vet Clin Equine 34 (2018) 485–498 https://doi.org/10.1016/j.cveq.2018.07.006 vetequine.theclinics.com 0749-0739/18/Published by Elsevier Inc. 486 Leise Removal of dirt and debris from the wound is important, because soil has been found to have factors that potentiate infection. In the presence of soil, only 100 bacteria are necessary to elicit infection.3 Therefore, topical cleansing of wounds is an important part of wound management. Pressure lavage can be used to help clean and decontaminate wounds; however, it is important not to be too aggressive. Lavage pressures over 20 psi can damage tissue and drive bacteria deeper into a wound bed. Use of a 35-mL syringe with a 19-gauge needle exerts a pressure of 7 psito15psiatawoundsurface(Fig. 1).3,4 Additional cleansing of the wound after the initial treatment may be unnecessary, because it may damage the delicate tissue around the wound margin and remove wound exudate that can have beneficial factors for wound healing. ANTISEPTICS Antiseptics can be used alone or added to lavage fluid to reduce microbial content within a wound (Fig. 2). Topical antiseptics should have a broad spectrum of activity, controlling both resident and contaminating flora, including bacteria, fungi, and vi- ruses on the wound and surrounding skin. Antiseptics reduce microbial numbers through mechanical and/or chemical properties. The addition of antiseptics, such as povidone-iodine or chlorhexidine, into lavage fluid is a common practice in equine wound management. It is important, however, to dilute these products to appropriate levels (0.1%–0.05% solutions) that minimize deleterious effects to the wound and surrounding tissue prior to use, because many of these antiseptic agents have negative effects on wound healing at higher concentrations. Fig. 1. Normal saline (0.9% sodium chloride) administered as a pressure lavage using an 18- gauge needle and 35-mL syringe will deliver between 8 psi and 15 psi to the wound surface. Topical Wound Medications 487 Fig. 2. Development of a biofilm occurs when microorganisms (purple) colonize into com- munities on the surface of wounds, producing a protective extracellular matrix (green) that encases the organisms, preventing antimicrobial penetration. Hydrogen Peroxide 3% Hydrogen peroxide 3% is used to clean wounds, producing an effervescent effect on application. The antimicrobial benefits of hydrogen peroxide in vivo have been ques- tioned because it is rapidly broken down into water and oxygen, via the enzyme cata- lase, on contact with organic tissue. Bacterial production of catalyze likely limits the microbial killing ability of hydrogen peroxide. Due to its liberation of oxygen, hydrogen peroxide has been recommended for use in deep puncture wounds where Clostridium infections may be of concern. Numerous studies suggest that hydrogen peroxide is cytotoxic. Therefore, it is not recommended for use in the general cleaning of equine wounds. Use of a hydrogen peroxide cream has demonstrated improved healing of equine wounds. Experimentally, application of 1% hydrogen peroxide cream (LHP, Bioglan AB, Malmo¨ , Sweden) resulted in faster healing of equine wounds and reduced bacterial colonization compared with controls.5 Povidone-Iodine 10% Povidone-iodine is an iodophor and depends on the release of free iodine to be acti- vated.3,6 Iodophors were developed to stabilize iodine in solution and subsequently allow the sustained release of iodine. The antimicrobial action of povidone-iodine occurs rapidly, killing a variety of bacterial strains within 20 seconds to 30 seconds. Although the mechanism of action has not been fully elucidated, iodine damages essential cellular structures by attacking intracellular proteins, fatty acids, and nucle- otides.6 Iodine is inactivated by organic material; therefore, removal of dirt and debris is indicated prior to application of povidone-iodine. Prolonged microbial killing is also inhibited by the presence of organic material, such as blood and serum proteins, and effects on microbial killing is short lived. Povidone-iodine reportedly increased damage to vascular endothelium and caused thrombosis in rat wounds compared with other agents, including chlorhexidine.7 Epithelialization can also be delayed when povidone-iodine is used.6 Therefore, 10% povidone-iodine should be diluted to concentrations of 0.1% to 0.2% to minimize cytotoxicity to the surrounding tissue. The 488 Leise addition of 10 mL to 20 mL in 1 L of saline is recommend for cleaning equine wounds. It is important that scrub formulations are not used to clean wounds because the deter- gent component has increased cytotoxic effects on exposed tissues. Chlorhexidine Gluconate and Chlorhexidine Diacetate 2% Chlorhexidine is one of the most commonly used antiseptics in veterinary medicine. It is a biguanide antiseptic that is positively charged and exerts its antimicrobial effects by reacting with the negative cell surface membrane, thereby disrupting and subsequently killing microorganisms. It has a wide antimicrobial spectrum and a prolonged residual effect. Unlike povidone-iodine, the presence of organic material has no effect on the microbial killing ability of chlorhexidine. Bacterial resistance has developed through acti- vation of efflux pumps, which are intermembrane protein channels developed by bacteria to remove various antibiotics and biocides. In particular, some Pseudomonas and Proteus spp have been found resistant to chlorhexidine.8 Chlorhexidine can be cytotoxic; therefore, it must be diluted prior to use. A 0.05% solution is recommended for lavage and cleaning of wounds. A 1:40 dilution of chlorhexidine gluconate 2% can be made by adding 25 mL of 2% chlorhexidine to 975 mL of sterile saline. Chlorhexidine should not be used near the eye or open joints, as its use can result in corneal edema and scaring, affecting vision and synovial inflammation and abundant fibrin accumula- tion, respectively.9 Overall, chlorhexidine is recommended for use over povidone- iodine, because it is less cytotoxic and has superior bacterial killing. Dakin’s Solution Dakin’s solution or sodium hypochlorite, also known as bleach, is available in varying concentrations ranging from full strength at 0.5% to 1/40 strength of 0.0125%. Sodium hypochlorite exerts its antibacterial effects by liberating chlorine into the tissues. Although bleach has been historically used to clean wounds in battlefield situations, Dakin’s solution is cytotoxic; therefore, low dilutions (1:50 dilution resulting in 0.00025% solution) of the 0.0125% concentration are recommended. This solution is not stable and is inactivated by light and heat. Due to the instability and cytotoxic properties, sodium hypochlorite is not commonly used or recommended to treat equine wounds. Hypochlorous Acid Similar to hypochlorite, hypochlorous acid exerts its antimicrobial effects through

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