Silver In Wound Care: What You Should Know

There has been a resurgence of silver dressings in wound care in recent years due to the antimicrobial activity of silver, its safety and a lack of resistance. Accordingly, this author discusses silver dressing selection, shares insights on nanocrystalline silver and assesses the current literature on silver in wound care.

Silver has inundated the field of wound care in the last decade in the form of different products and dressings. This resurgence can in part be attributed to the resistant strains of bacteria forming against commonly used antibiotics. We now know that even minute concentrations of silver have a bactericidal effect.1 This has prompted the development of multiple silver-containing wound care products such as hydrogels, hydrofibers, foams, hydrocolloids, gauze and alginates.

   The use of silver can play a major role in the infected, colonized and/or chronic wound. Silver is widely considered a broad-spectrum agent, which is effective against gram-positive organisms, gram-negative organisms and fungi as well as resistant strains of bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci.1-5

   Silver exerts its antimicrobial activity in the form of ionic silver (Ag+ ions). Silver facilitates the growth of proteins through a combination with chloride in tissues and by blocking the microbial respiratory chain system.4

   The antimicrobial activity of Ag+ ions is generally attributed to four mechanisms.2 Ionic silver:
• binds to the bacterial cell membrane, damaging it and interfering with various receptors;
• disrupts bacterial electron transport, impeding the production of adenosine triphosphate;
• impairs cell replication by binding to bacterial DNA; and
• triggers the intracellular formation of insoluble compounds with certain nucleotides, proteins and the amino acid histidine, making them unavailable as intracellular building blocks.

   Importantly, silver can also decrease matrix metalloproteinases (MMPs) on the surface of wounds. This results in an increase in surface calcium, an enhancement of microbial effects and a decrease of inflammation within the wound. As we know, the proteolytic property of the MMPs is essential during wound healing to facilitate cell migration and remove debris.

   However, excessive accumulation and activation of MMPs versus their inhibitors can compete with cell proliferation, angiogenesis and matrix proteins necessary for cell migration.6 Bacteria in chronic wounds also produce MMPs that may be responsible for the increasing tissue damage that can lead from critical colonization to infection. By reducing the number of bacteria and the associated inflammatory response it creates, a dressing containing nanocrystalline silver may facilitate wound healing.6

What Qualities Should You Look For In Silver Dressings?

There are four main categories of silver-containing dressings. The actions of these silver dressings include:

• releasing silver into the wound bed for antimicrobial action;
• absorbing wound exudate into the dressing fabric where the silver then exerts its bactericidal activity (into the dressing but not necessarily the wound);
• absorbing wound exudate and releasing silver into the wound bed for antimicrobial activity; and/or
• releasing silver sulfadiazine into the wound that cleaves in the presence of wound exudate and liberates the silver and sulfadiazine moiety.5

   Therefore, when choosing a silver containing dressing, the physician should have an idea of what action the silver product is having on that particular wound and adjust accordingly. Silver compounds in various wound products differ in the manner and speed with which they release the bactericidal silver ions.3 Silver-impregnated, slow release dressings release minute concentrations of silver that quickly bind up by the chloride in the wound exudate.

   The total amount of silver in a dressing, as well as its crystalline structure, contributes to how much and how quickly silver disperses from the dressing onto the wound surface. If a given amount of silver divides among a large number of smaller crystals, its chemically active surface area will be greater than when the same amount divides among fewer, larger crystals. There is ongoing debate and continued disagreement when it comes to whether a higher concentration or a larger total amount (or both) of silver in a dressing would result in greater quantities of biologically active silver in the dressing and on the wound surface.2

   One side of the argument suggests that when excess chloride is present, it may be possible to overcome the current wound environment with a dressing containing a massive amount of silver. These proponents suggest that as the chloride binds to the silver and becomes inactive (AgCl), the remaining silver ions will have an antimicrobial effect on the wound environment. Others have stated it is the amount of available soluble silver in a dressing that determines the efficacy of the dressing.2 Some silver product companies will boast about how much silver their dressing contains. However, it has still not been shown that a larger amount of silver in a dressing necessarily results in better clinical outcomes.

   Lipsky and colleagues describe both advantages and disadvantages on the use of topical antiseptic products for chronic wounds.3 In reference to silver products, advantages include the ability to provide sustained levels of active silver ions and that application is infrequent, and can be less painful. In addition, microbial resistance is rare and adverse effects are minimal in comparison to silver nitrate. Another advantage is the variety of products adaptable to different types of wounds.

   When it comes to disadvantages, the levels of silver ions at the wound interface is not well defined. Also bear in mind that topical antiseptic products may cause silver staining of the surrounding tissues and may delay epithelialization.3 In addition, such products can be relatively expensive and there are currently very few published comparative trials.

   Lipsky and colleagues go on to state that silver dressings may be useful for subclinically infected, highly colonized wounds or for wounds being prepared for skin grafting.3 However, the authors note that one should not substitute silver dressings for non-medicated dressings for uninfected wounds.

A Closer Look At The Impact Of Nanocrystalline Silver

Newer silver formulations are manufactured in the form of high-density polyethylene mesh with nanocrystalline silver. There are currently three types of wound products containing nanocrystalline silver: Acticoat™, Acticoat 7™ and Acticoat Absorbent™ (all Smith and Nephew).

   Nanocrystalline (NC) silver utilizes nanotechnology to release clusters of highly reactive silver particles that are extremely small.7 Research has found the formulations within these NC products to be equally effective at preventing infections in comparison to older formulations but they also allow a higher interval of time between dressing changes.4 In some cases, the specific properties of some components in the NC dressings rendered the medication highly effective.4 This option can provide physicians with the possibility to choose the most appropriate dressing according to key factors (such as control of bioburden and wound exudate) affecting the local wound situation.

   Sibbald and colleagues looked at chronic venous stasis wounds.6 They found that patients with an increased baseline bacterial burden and an associated increase in neutrophils benefited more from the antibacterial action of NC silver dressings and the resulting reduction in inflammation.

   When the silver product becomes moist within a wound, the small crystals of microscopic silver rapidly dissolve in the wound, releasing both ionic and metallic silver: Ag+ and Ag°. The antimicrobial potential of nanocrystalline silver is evident in its ability to establish a relatively high ionized-silver concentration on the wound surface within minutes.6 This silver concentration is sustained over time with the release of new ionized silver particles from the nanocrystalline molecular clusters with many silver interfaces.

   What is important to appreciate is that with the use of silver dressings, the silver ions can be released over time. The result is a decrease in the need for daily dressing changes, which is more cost effective. This is advantageous to the sensate patient and can decrease the amount of open exposure the wound may have to other contaminants, especially those found within the hospital.

   As one of the recently introduced silver dressings, NC silver is composed of a urethane film onto which nanocrystalline elemental silver is deposited. This particular formulation provides a sustained release of elemental silver with the possibility to delay dressing changes up to once weekly.

   Furthermore, recent studies have also suggested that NC silver has a greater ability to prevent burn infections in comparison to older formulations. Gravante and co-workers performed a meta-analysis on data from randomized trials on patients with burns.4 They found that nanocrystalline silver had a 2.9-fold decreased incidence of infection in burns in comparison to older silver formulations such as silver sulfadiazine and silver nitrate.

Should You Be Concerned About Toxicity Or Resistance?

Thus far, in the clinical setting, there have been no reports of bacterial resistance to silver.

   Percival and co-workers evaluated the potential for silver resistance.8 The results of this study suggested that the presence of silver resistance genes is rare and that genetic resistance does not necessarily translate to phenotypic resistance to silver. While one should monitor silver resistance in wound care, the threat of widespread resistance is low and silver-containing dressings remain an extremely important tool in managing wound infection as well as bacterial bioburden.

   Toxicity while utilizing a silver product has also never been shown in the wound care setting. The only reported side effect of silver use has been the discoloration of skin.9 This is called argyria and is characterized by the deposition of particles of silver sulfide or silver selenide on the skin. However, this is not regarded as a health risk or manifestation of toxicity.

   Fong and colleagues concluded that although there is no in vivo evidence to suggest NC silver is toxic to human keratinocytes and fibroblasts, there has been in vitro evidence to suggest this is the case.7 Thus, one should use these dressings cautiously over epithelializing and proliferating wounds. Future clinical research involving nanocrystalline silver technology may provide physicians a better understanding of its applications and possible toxicity in a clinical setting.

Is There Enough Evidence About Silver Dressings?

Although silver dressings have been the subject of many anecdotal reports and case series, there have been few well-designed clinical trials involving these dressings. In general, available data make it difficult to assess the efficacy of topical antimicrobials for chronic wounds as most studies are suboptimal and have varying designs that are not easily comparable.3 Clinicians must rely on researchers, the wound care community at large and product manufacturers to provide information and insight into the merits and drawbacks of any new dressing, technique or technology.2

   Unfortunately, many dressings, including the majority of silver-containing dressings, have not undergone testing in ways that provide clinically valuable information. In vitro tests are important as are those studies using animal models, but only properly executed, prospective, comparative, randomized clinical trials can provide information that may be used as a guideline in a clinical setting.

   In a retrospective study on wounds of various etiologies, Moore and co-workers found that the use of a silver-coated polymeric substrate seems to be effective as a primary wound care product for patients with active wounds.1 However, they noted that more studies are needed to characterize the product’s effectiveness in comparison with other dressing types.

In Conclusion

The popularity of silver in the wound care setting continues to increase due to its safety, the lack of resistance reported thus far and its broad-spectrum antimicrobial activity. However, the fact remains that there is no strong clinical evidence in the literature as of yet supporting the use of a silver product on all chronic wounds.

   What the literature has demonstrated is that silver remains effective against many strains of bacteria including resistant strains and it may play a role in the reduction of inflammation within the wound. Silver products have not been found to be toxic or harmful to a wound, and may expedite the healing of chronic wounds through anti-inflammatory and antimicrobial effects.

Dr. Cornell is currently doing a Fellowship in Diabetic Limb Salvage at Georgetown University Hospital in Washington, D.C.

   For further reading, see “What You Should Know About Using Silver Products In Wound Care” in the November 2004 issue of Podiatry Today or “Key Considerations For Utilizing Silver Dressings” in the May 2006 issue.

   To access the archives, visit www.podiatrytoday.com.

References:

1. Moore R, Liedl D, Jenkins S, Andrews K. Using a silver-coated polymeric substrate for the management of chronic ulcerations: the initial Mayo Clinic experience. Adv Skin Wound Care 2008; 21(11):517-20. 2. Hermans, MH. Silver-containing dressings and the need for evidence. Adv Skin Wound Care 2007; 20(3):166-173. 3. Lipsky, BA, Hoey, C. Topical antimicrobial therapy for treating chronic wounds. Clin Infect Dis 2009; 49(10):1541-9. 4. Gravante G, Caruso R, Sorge R, Nicoli F, Gentile P, Cervelli V. Nanocrystalline silver: a systematic review of randomized trials conducted on burned patients and an evidence-based assessment of potential advantages over older silver formulations. Ann Plast Surg 2009; 63(2):201-5. 5. Granick M, Gamelli R: Surgical wound healing and management. In: Mosti G, Mattaliano V (eds.): The Debridement of Chronic Vascular Leg Ulcers. Ch. 12, Informa Healthcare Inc., 2007, pp. 120-121. 6. Sibbald RG, Contreras-Ruiz J, Coutts P, Fierheller M, Rothman A, Woo, K. Bacteriology, inflammation, and healing: a study of nanocrystalline silver dressings in chronic venous leg ulcers. Advances Skin Wound Care 2007; 20(10):549-557. 7. Fong J, Wood F. Nanocrystalline silver dressings in wound management: a review. Int J Nanomedicine 2006; 1(4):441-8. 8. Percival SL, Woods E, Nutekpor M, Bowler P, Radford A, Cochrane C. Prevalence of silver resistance in bacteria isolated from diabetic foot ulcers and efficacy of silver-containing wound dressings. Ostomy Wound Manage. 2008;54(3):30-40. 9. Lansdown AB. Silver in health care: antimicrobial effects and safety in use. Curr Probl Dermatol. 2006; 33:17-34. 10. Martin JM, Zenilman JM, Lazarus GS. Molecular microbiology: new dimensions for cutaneous biology and wound healing. J Invest Dermatol. 2010; 130(1):38-48. 11. Davis SC, Martinez L, Kirsner R. The diabetic foot: the importance of biofilms and wound bed preparation. Curr Diab Rep. 2006; 6(6):439-45. 12. James GA, Swogger E, Wolcott R, Pulcini ED, Secor P, Sestrich J, Costerton JW, Stewart PS. Biofilms in chronic wounds. Wound Repair Regen. 2008; 16(1):37-44.