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Cytotoxicity And Wound Care: What Clinicians Should Know

Silver is a cytotoxic agent that has been used in wound care for millennia. The history of silver use can be traced back to ancient Egypt where it was applied topically over the wounds to promote healing. Despite the lack of available research at the time, silver was considered an effective medicinal agent. After the discovery of penicillin in 1928, the use of silver and silver-based products in healthcare started to decline. However, it remained popular during the First World War.

The emergence of antibiotic-resistant organisms has led to a renewed interest in the use of silver in wound care. Wound care specialists and podiatrists are now increasingly employing silver-based dressings in their wound care practice. This article describes the role of cytotoxic silver and silver-based dressings in modern wound care.

Role of Silver As A Topical Antimicrobial Agent

Silver dressings are gaining renewed popularity because of their cytotoxic effect on bacteria. It is effective against a wide range of bacteria including antibiotic-resistant strains such as methicillin-resistant Staph Aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Silver is also highly effective against other pathogens such as viruses and fungi. 

The antimicrobial property of silver depends on its availability in ionic form. Elemental silver is non-reactive against bacteria and therefore would not exert a cytotoxic effect. 

Only positively charged silver ions (Ag+) are bactericidal. To become positively charged, silver must lose an electron. It can do so when it is exposed to an aqueous environment such as that which is present in the wound exudate.

By initially binding to the bacterial cell wall, silver ions can prevent oxygen and nutrient transport into the bacterial cell. Later, they migrate inside the cell where they bind with the bacterial DNA and effectively inhibit bacterial replication. 

Silver-based dressings are easy to use and provide a sustained release of silver to the wound bed. In addition to their antimicrobial property, silver dressings also play a role in the facilitation of moist wound healing and autolytic debridement. 

When To Use Silver-Based Dressings?

Early identification and treatment of wound infection is a critical component of effective wound care. This is particularly important in chronic wounds as untreated wound infection can lead to severe complications such as sepsis or systemic infection. Wound care specialists and podiatrists should therefore regularly assess the wound for signs of infection.

The TILI (Therapeutic Index for Local Infections) score can be a helpful diagnostic tool for the early detection of wound infection. It is a standardized tool that can be easily incorporated into practice by caregivers and healthcare staff. Silver-based dressings are only indicated when there is clinical evidence of localized or systemic infection. Therefore, the TILI score can be used by clinicians to determine whether silver dressings are indicated.

For localized wound infection, silver-based dressings are sufficient. However, in the presence of widespread infection, they should be used along with systemic antibiotics. 

When To Avoid Silver-Based Dressings?

Silver-based dressings should be avoided when there is no clinical evidence of localized or systemic infection. Other contraindications to silver-based dressings include:

  • Clean surgical wounds with a low risk of infection
  • Absence of localized infection or biofilm
  • Pregnancy 
  • Allergy or hypersensitivity to silver or silver-based products
  • Chronic wounds healing in accordance with the patient profile
  • They should not be used when patients are undergoing MRI or radiotherapy 

How To Use Silver Dressings?

Silver-based products are not recommended to be used long term. In general, antimicrobial treatment should initially be used for two weeks. Later, the wound should be assessed and evaluated for the suitability of further continued treatment with silver dressings. Some general principles to be kept in mind when using silver-based antimicrobial treatment are described below:

  • Clinicians should determine and document the rationale for using silver-based antimicrobial agents. The TILI score can be a helpful tool for clinicians to determine the indication of antimicrobial agents.
  • Wounds treated with silver-based agents should be evaluated after two weeks. If the wound is not healing, wound care specialists can continue to use silver in wound care.
  • The primary aim of silver-based dressings is to reduce wound bioburden and infection. Therefore, they should not be considered 'healing' agents. However, reduced infection rates can result in improved wound healing. Studies have demonstrated the excellent efficacy of silver against wound infections.
  • If the wound is not improving, alternate antimicrobial agents should be considered.
  • Clinicians should carefully read the manufacturer's instructions. Silver dressings should be prescribed based on the individual needs of the patient.

Is Silver Safe To Use In Wound Care?

The cytotoxic nature of silver has the potential to raise concerns regarding its safety. Several studies were done to determine the safety of silver for wound care. Fortunately, silver has been found to be safe and non-toxic for human use. In addition, very little silver is systemically absorbed from the wound dressings. Only a small amount of ionic silver is made available by the dressings which mainly exerts its cytotoxic effect against external pathogens.

Silver is mainly excreted from the human body via the biliary route, while the remainder is excreted in the urine. The local deposition of silver at the wound site can result in 'argyria'. It refers to the greyish-black discoloration of the skin resulting from long-standing silver deposition. However, there has been minimal evidence of systemic toxicity with the use of silver dressings.

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