Amanda R. Budak, PhD, RN, CBN
Silver is growing in use in the form of advanced silver dressings for the management of bacterial infections that may occur in hospital acquired infections and surgical site infections. Due to the increased use, there have been concerns amongst clinicians regarding the risk of silver toxicity. Based on this, an extensive review of the literature was conducted to address these concerns.
Silver based dressings have been studied extensively in animal models using hairless guinea pigs and mini pigs to determine the blood and tissue absorption of silver ions, and to monitor for clinically significant detrimental effects. In one sentinel study looking at silver nylon plated dressings and nanocrystalline dressings, there were negligible levels of silver ions noted in the blood, liver, kidney or spleen.1 In this study - animals were subjected to sulfur mustard burns and a silver-plated nylon dressing was applied every 7 days until healing or until day 60 when the animals were euthanized.
At the time of autopsy, blood and tissue tissue levels were less than 0.003 ug/g in the blood, less than 0.002 ug/g in the liver and spleen and less than 0.03 in the kidney.1
Silver is a naturally occurring element. Humans have used silver for jewelry, currency, eating utensils and body adornment (body piercing) for at least 5000 years. The use of silver for coins and for food serving is mentioned in the first books of the Old Testament (Genesis Chapters 13:2, 20:16, 23:15, 24:35, 24:53, 33:19, 37:28, 42:25, 42:27, and 44:2). The earliest medical applications of silver date back three Millenia: In 335 BC, Alexander the Great placed silver coins into water containers to prevent spoilage and retard algae growth during campaigns. American settlers heading west in the 1800s placed silver coins in water barrels for the same reason. In the 1960s, NASA investigated the use of silver ion for water purification. The Apollo 11 spacecraft, which landed on the moon 50 years ago, used ionic silver to purify their drinking water.
Silver is not an eye or skin irritant, mutagen or carcinogen.3 Unlike nickel, true allergy to silver is exceptionally rare. Unlike mercury, silver does not concentrate in aquatic animals.
Silver is not a recognized trace metal in humans and has no known nutritional or physiologic role in humans. Silver is normally found in the body at low levels secondary to ingestion and inhalation from natural sources. Normal silver levels in humans include a blood concentration of <2.3 ug / L (micrograms per liter) and a daily urinary excretion of 2 micrograms per day 3. The US Environmental Protection Agency allows silver in drinking water up to 50 parts per billion and recommends daily intake of less than 0.005 milligrams/kg per day.3 Compare this with blood silver levels described above which show levels of < 0.003 ug/g when Silverlon is left on open wounds for extended periods.1
Older silver compounds such as silver nitrate or silver sulfadiazine are associated with increased blood or organ levels of silver ion, while Silverlon is not. As much as 10% of silver sulfadiazine can be absorbed through partial thickness burns, with blood silver levels of up to 300 micrograms per liter measured.3 When silver sulfadiazine is applied to large body surface area burns for extended periods, urinary excretion of silver may increase a thousandfold3. Silver nitrate applied to open wounds results in silver ions being identified in liver and kidney.3 Again, this does not occur with Silverlon. We have performed multiple animal studies with Silverlon and found levels of silver ions <0.003 ug/g essentially in organs (kidney, liver and spleen) or in the blood stream. This effect is consistent in multiple species (pigs, hairless guinea pigs, rats); in multiple types of wounds (thermal burns, chemical burns, open wounds) and in both partial thickness and full thickness burn injury.
Silver ions, as provided in Silverlon, does not create local skin discoloration, although other products based on nanocrystalline silver may. Silverlon has also received an MR conditional indication for use in X-rays, CT Scans, and MRI (as per our recent 510(k) 180570, the indication is MR Conditional).
Silver’s antimicrobial effect is only realized when silver interacts with moisture. When in the presence of any type of moisture, silver ions are released within the dressing. It is Silver in its ionic state (Ag+1) that generates antimicrobial activity. This activity occurs by inhibiting three mechanisms of cellular function; cellular metabolism, cellular respiration and cellular replication. It is thought that these multiple mechanisms of action provide the broad spectrum antimicrobial activity and also decreases the potential for antimicrobial resistance.2
Silver has been used and explored in a variety of ways, including in silver coated endotracheal tubes to prevent ventilator associated pneumonia and in urinary catheters to prevent hospital acquired urinary tract infections, all with inconsistent findings of effectiveness.3,4 Some products such as silver in hospital curtains and in wall paint have been considered for use in the healthcare setting to decrease the potential risk of spread of bacteria.5
Most products used in healthcare that contain silver or silver compounds come into contact with human skin. With concern for silver absorption and toxicity, clinical and experimental studies have been conducted and indicate that percutaneous absorption of silver is exceedingly low6. Toxicity has been reported with occupational exposure to silver and it is expected that in this scenario the silver is absorbed into the system through inhalation or exposure to contaminated food and drinking water. Lethal oral concentrations of silver nitrate in humans have been estimated at approximately 10g, but this is largely attributable to the strong acidity of the silver nitrate — and it is the nitrate anion released and not the absorption of silver ions ( Ag+) that is thought to contribute to the mortality6. Typical silver levels in humans include a blood concentration of <2.4ug/L.7
Silver has a long and compelling story in history as an antimicrobial in social and human health care. It is used in water purification, wound care, bone prostheses, reconstructive orthopedic surgery, cardiac devices, catheters and surgical appliances. Innovation and advances in manufacturing and biotechnology have provided the technology to enable the incorporation of ionizable silver in advanced surgical dressings to reduce the risk of nosocomial infections. The antimicrobial action of silver is proportional to the amount of Silver (Ag(+)) released and the availability of that silver to interact with pathogens. To be effective, metallic silver must interact with moisture, which releases silver ions. This moisture can be in the form of saline, sterile water, body fluids or tissue exudates. Bacterial sensitivity to silver is genetically determined and relates to the levels of intracellular silver uptake and the ability of silver ions to interact with pathogens and irreversibly inhibit key enzyme systems; such as the three mechanisms of actions discussed earlier. There is very little evidence of silver toxicity in the human body, and minimal risk is expected with clinical exposure. Silver is absorbed into the human body and enters the systemic circulation as a protein complex to be eliminated by the liver and kidneys. This complex mitigates the cellular toxicity of silver and has been reported to contribute to tissue repair.8
Multiple studies across multiple animal platforms1,2 have shown that Silver plated nylon dressings do not result in any measurable accumulation of silver in the blood, liver, kidney, or spleen. The effect that these silver dressings can have on Surgical Site Infections (SSI’s) has been shown in multiple studies across multiple specialties.9-14 Another large-scale animal model study is currently under way to evaluate silver absorption.
Indications for Use:
Silverlon Island Wound Dressings and Silverlon Wound Pad Dressings are multi-layer, sterile, non-adherent, antimicrobial barrier wound dressings for the management of infected wounds, as the silver in the dressing provides an antimicrobial barrier that may be helpful in managing these wounds.
Silverlon® Dressings should not be used on patients with 3rd degree burns or with known sensitivity to silver or nylon. For complete Instructions for use, please visit www.silverlon.com.
Amanda Budak, RN, CBN, PhD
Dr. Budak has over 25 years of nursing practice in clinical, leadership and management roles. This experience encompasses med/surg, trauma, critical are, emergency medicine, burns, clinical research and clinical operations. She received her Bachelors, Masters and Doctor of Philosophy degrees from the Medical University of South Carolina, College of Nursing, has authored numerous publications, and is a sought after speaker by associations and healthcare institutions.
1. Barillo DJ, Croutch CR, Reid F, Culley T, Sosna W, Roseman J. Blood and Tissue Silver Levels Following Application of Silver-Based Dressings to Sulfur Mustard Chemical Burns. Journal of burn care & research : official publication of the American Burn Association. 2017;38(5):e818-e823.
2. Marx DE, Barillo DJ. Silver in medicine: the basic science. Burns : journal of the International Society for Burn Injuries. 2014;40 Suppl 1:S9-s18.
3. Tokmaji G, Vermeulen H, Muller MC, Kwakman PH, Schultz MJ, Zaat SA. Silvercoated endotracheal tubes for prevention of ventilator associated pneumonia in critically ill patients. The Cochrane database of systematic reviews. 2015(8):Cd009201.
4. Akcam FZ, Kaya O, Temel EN, Buyuktuna SA, Unal O, Yurekli VA. An investigation of the effectiveness against bacteria of silver-coated catheters in short-term urinary catheter applications: A randomized controlled study. J Infect Chemother. 2019.
5. Luk S, Chow VCY, Yu KCH, et al. Effectiveness of antimicrobial hospital curtains on reducing bacterial contamination-A multicenter study. Infection control and hospital epidemiology. 2018:1-7.
6. Lansdown AB. A pharmacological and toxicological profile of silver as an antimicrobial agent in medical devices. Adv Pharmacol Sci. 2010;2010:910686.
7. Wan AT, Conyers RA, CoombsCJ, Masterton JP. Determination of silver in blood, urine, and tissues of volunteers and burn patients. Clin Chem. 1991;37(10 Pt 1):1683-1687.
8. Lansdown AB. Silver in healthcare: antimicrobial effects and safety in use. Current problems in dermatology. 2006;33:17-34.
9. Karlnoski R, Abboud EC, Thompson P, Oxner AZ, Sinnott JT, Marcet JE. Reduction in Central Line-Associated Bloodstream Infections Correlated With the Introduction of a Novel Silver-Plated Dressing for Central Venous Catheters and Maintained for 6 Years. Journal of intensive care medicine. 2017:885066617745034.
10. Tisosky AJ, Iyoha-Bello O, Demosthenes N, Quimbayo G, Coreanu T, Abdeen A. Use of a Silver Nylon Dressing Following Total Hip and Knee Arthroplasty Decreases the Postoperative Infection Rate. Journal of the American Academy of Orthopaedic Surgeons Global research & reviews. 2017;1(7):e034.
11. Krieger BR, Davis DM, Sanchez JE, et al. The use of silver nylon in preventing surgical site infections following colon and rectal surgery. Diseases of the colon and rectum. 2011;54(8):1014-1019.
12. Siegel HJ, Herrera DF, Gay J. Silver negative pressure dressing with vacuum-assisted closure of massive pelvic and extremity wounds. Clinical orthopaedics and related research. 2014;472(3):830-835.
13. Epstein NE. Do silver impregnated dressings limit infections after lumbar laminectomy with instrumented fusion? Surgical neurology. 2007;68(5):483-485; discussion 485.
14. Huckfeldt R, Redmond C, Mikkelson D, Finley PJ, Lowe C, Robertson J. A clinical trial to investigate the effect of silver nylon dressings on mediastinitis rates in postoperative cardiac sternotomy incisions. Ostomy/wound management. 2008;54(10):36-41.