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Silver in Wound Care—Friend or Foe?: A Comprehensive Review

Khansa, Ibrahim MD*,†; Schoenbrunner, Anna R. MD; Kraft, Casey T. MD; Janis, Jeffrey E. MD, FACS

Plastic and Reconstructive Surgery – Global Open: August 2019 - Volume 7 - Issue 8 - p e2390
doi: 10.1097/GOX.0000000000002390
Special Topic
Open
United States

Background: Due to its strong antimicrobial activity, silver is a commonly used adjunct in wound care. However, it also has the potential to impair healing by exerting toxic effects on keratinocytes and fibroblasts. The published literature on the use of silver in wound care is very heterogeneous, making it difficult to generate useful treatment guidelines.

Methods: A search of high-quality studies on the use of silver in wound care was performed on PubMed. A detailed qualitative analysis of published articles was performed to evaluate the evidence for the use of silver in infected wounds, clean wounds, burns, and over closed surgical incisions.

Results: Fifty-nine studies were included in this qualitative analysis. We found that, overall, the quality of the published research on silver is poor. While there is some evidence for short-term use of dressings containing nanocrystalline silver in infected wounds, the use of silver-containing dressings in clean wounds and over closed surgical incisions is not indicated. Negative-pressure wound therapy accelerates the healing of contaminated wounds, especially when silver is used as an adjunct. For burns, silver sulfadiazine slows healing and should not be used. Instead, nanocrystalline silver, or alternatives such as octenidine and polyhexanide, lead to less infection and faster healing.

Conclusions: In infected wounds, silver is beneficial for the first few days/weeks, after which nonsilver dressings should be used instead. For clean wounds and closed surgical incisions, silver confers no benefit. The ideal silver formulations are nanocrystalline silver and silver-coated polyurethane sponge for negative-pressure wound therapy. Silver sulfadiazine impairs wound healing. Proper use of silver-containing dressings is essential to optimize wound healing.

From the *Division of Plastic and Reconstructive Surgery, Nationwide Children’s Hospital, Columbus, Ohio

Department of Plastic and Reconstructive Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Published online 9 August 2019.

Received for publication March 28, 2019; accepted June 19, 2019.

Disclosure: Dr. Janis receives royalties from Thieme Publishing. Drs. Khansa, Kraft, and Schoenbrunner have no financial disclosures.

Jeffrey E. Janis, MD, FACS, Department of Plastic and Reconstructive Surgery, The Ohio State University Wexner Medical Center, 915 Olentangy River Rd, Columbus, OH 43212, Phone: (614) 366-1242, Fax: (614) 293-9024, E-mail: jeffrey.janis@osumc.edu

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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INTRODUCTION

The usefulness of silver for wound treatment has been known since 69 B.C.1 While silver metal (Ag) has no medicinal activity, silver ion (Ag+) has a broad antimicrobial spectrum, and is cytotoxic to bacteria, viruses, yeast, and fungi.2 Ag+ binds to DNA, RNA, and various proteins, leading to cell death via multiple mechanisms,3 such as protein and nucleic acid denaturation, increased membrane permeability, and poisoning of the respiratory chain.4 For this reason, resistance against the silver ion has only rarely been reported.5–7

The past few decades have seen a renewed interest in silver as a topical antimicrobial agent. Silver sulfadiazine (SSD) is a very widely used silver formulation, especially in burns. More recently, dressing with nanocrystalline silver has been developed. These novel dressings release silver ions into the wound in a sustained fashion.

While the silver ion has great antimicrobial and bactericidal properties, it is also toxic to fibroblasts when present in high concentration.1,16,17 Injudicious use of silver-containing dressings can lead to impaired wound healing.45 It is imperative, therefore, that guidelines be developed on the proper use of silver-containing dressings.

Our purpose in this study was to evaluate the existing evidence on the use of silver in wound care. The questions that we sought to answer were:

  • 1) What is the quality of the published studies on the use of silver in wound care?
  • 2) What are the advantages and disadvantages of various silver delivery systems?
  • 3) What is the evidence for the use of silver-containing dressings in infected and heavily contaminated wounds?
  • 4) What is the evidence for the use of silver-containing dressings in clean and clean-contaminated wounds?
  • 5) What is the evidence for the use of silver-containing dressings in burns?
  • 6) What is the evidence for the use of silver-containing dressings over closed surgical incisions?
  • 7) What is the optimal strategy for the use of silver-containing dressings?
  • 8) How does silver compare to alternative, lesser known agents?
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METHODS

A PubMed literature search was performed using the following search parameters: silver AND (antimicrobial OR antibacterial) AND wound AND randomized; Silver AND epithelialization AND randomized; Silver AND negative pressure. The results were screened manually to exclude articles that were not relevant to our study (not about wound care), not in English, or which did not compare a silver-containing product to another product. We also excluded clinical studies with fewer than 20 patients. The articles were manually screened and duplicates were excluded. The remaining articles were analyzed in detail qualitatively, to extract answers to our study questions. The articles analyzed in this study are shown in Table 1.

Table 1. - Summary of the Articles Included in This Study
Article Type of Study Level of Evidence No. Subjects (for Human Studies) Purpose Results
Infected wounds Abarca-Buis, 2014 Basic science - - Evaluate silver ion elution from silver-coated polyurethane NPWT sponge Silver ion concentration in wound exudate rises over several days
Ellenrieder, 2015 Basic science - - Evaluate effectiveness of polyurethane versus silver-coated polyurethane NPWT sponges at reducing MRSA colony counts NPWT with silver-coated polyurethane sponge decreases MRSA colony counts more than NPWT with polyurethane sponge
Ngo, 2012 Basic science - - Compare biofilm formation with polyurethane NPWT sponge versus silver-coated polyurethane NPWT sponge NPWT with polyurethane sponge reduces biofilm
NPWT with silver-coated polyurethane sponge reduces biofilm even more
Sachsenmaier, 2013 Basic science - - Compare activity of polyurethane NPWT sponge versus silver-coated polyurethane NPWT sponge against S. aureus and S. epidermidis Silver-coated polyurethane NPWT sponge achieves a larger zone of bacterial inhibition than plain polyurethane sponge
With silver-coated polyurethane NPWT sponge, wound silver level reaches a peak at 5 days
Stinner, 2011 Basic science - - Compare activity of polyurethane NPWT sponge versus silver dressing and polyurethane NPWT sponge against S. aureus and P. aeruginosa The addition of a silver dressing to polyurethane sponge enhances the antimicrobial activity of NPWT
Meekul, 2017 RCT 1 39 Compare healing, pain, and cost with silver alginate versus gauze Silver alginate reduces pain compared to gauze, but does not accelerate healing or decrease cost
Vermeulen, 2007 Systematic review 1 847 Compare healing and odor with silver-containing dressing versus plain foam Silver-containing dressing does not accelerate healing, but improves wound odor
Gunal, 2015 Retrospective 3 21 Compare polyurethane to silver-coated polyurethane sponges for NPWT for infected diabetic foot ulcers NPWT with polyurethane sponge accelerates the healing of diabetic foot ulcers
NPWT with silver-coated polyurethane sponge accelerates healing even more.
Qian, 2017 Basic science - - Compare healing with SSD versus plain cream for chronic wounds SSD slows epithelialization and increases hypertrophic scar formation
Applewhite, 2018 Review - - Evaluate healing with NPWT and promogran prisma in chronic wounds Promogran prisma accelerates healing due to its collagen component acting as a sacrificial substrate for proteases in the wound.
NPWT promotes granulation tissue formation
Innes, 2001 RCT 1 17 Compare epithelialization with Acticoat versus occlusive, silver-free dressing for skin graft donor sites Occlusive, silver-free dressing leads to faster epithelialization and better scar than Acticoat
Krasowski, 2015 RCT 1 80 Compare epithelialization with silver-containing dressing versus octenidine for lower-extremity ulcers Octenidine leads to faster healing and less pain than silver-containing dressing
Michaels, 2009 RCT 1 213 Compare healing with nanocrystalline silver versus non-silver-containing dressings for lower-extremity venous ulcers Nanocrystalline silver does not accelerate healing of lower-extremity venous ulcers
Norman, 2016 Systematic review 1 576 Compare healing with silver-containing dressings versus gauze for pressure ulcers Silver-containing dressings do not accelerate pressure ulcer healing
O’Meara, 2014 Systematic review 1 4,486 Compare healing with silver-containing dressings versus standard dressings for lower-extremity venous ulcers Silver-containing dressings do not accelerate lower-extremity ulcer healing
Storm-Versloot, 2010 Systematic review 1 2,066 Compare infection rates with silver-containing dressings versus non-silver-containing dressings for chronic wounds Silver-containing dressings do not reduce infection rates
Bergin, 2006 Systematic review 1 0 Evaluate effectiveness of silver-containing dressings for diabetic foot ulcers There are no good RCTs evaluating silver for diabetic foot ulcers
Chambers, 2007 Systematic review 1 1,108 Evaluate effectiveness of silver-containing dressings for lower-extremity ulcers Silver-containing dressings do not accelerate lower-extremity ulcer healing
Quality of evidence for silver is poor
Dumville, 2015 Systematic Review 1 336 Evaluate effectiveness of silver alginate for pressure ulcers Silver alginate does not accelerate pressure ulcer healing
Quality of evidence for silver is poor
Karr, 2013 Case series 4 20 Compare healing with polyurethane NPWT sponge versus Silverlong + polyurethane NPWT sponge for chronic wounds Adding Silverlon to NPWT reduces healing time and cost
Toussaint, 2015 Basic science - - Compare epithelialization with Mepilex Ag versus triple antibiotic ointment Triple antibiotic ointment achieves faster epithelialization and less scarring than Mepilex Ag
Selcuk, 2012 Basic science - - Compare activity of SSD, mupirocin, Acticoat, and octenidine against Acinetobacter baumannii Highest antimicrobial activity is achieved by Acticoat, followed by octenidine, then mupirocin, then SSD
Khorasani, 2009 RCT 1 30 Compare epithelialization with SSD versus aloe vera SSD leads to slower epithelialization
Shahzad, 2013 RCT 1 50 Compare epithelialization and pain with SSD versus aloe vera SSD leads to more pain and slower epithelialization
Baghel, 2009 RCT 1 78 Compare epithelialization and infection with SSD versus honey SSD leads to more infections and slower epithelialization
Shah, 2013 RCT 1 78 Compare epithelialization and infection with SSD versus honey SSD leads to more infections and slower epithelialization
Sami, 2011 RCT 1 50 Compare epithelialization and infection with SSD versus honey SSD leads to more infections and slower epithelialization
Mujalde, 2014 RCT 1 110 Compare epithelialization, cost and infection with SSD versus honey SSD leads to more infections, higher cost, and slower epithelialization
Mashhood, 2006 RCT 1 50 Compare epithelialization, pain and infection with SSD versus honey SSD leads to more infections, more pain, and slower epithelialization
Varas, 2005 RCT 1 47 Compare pain with SSD versus Acticoat SSD leads to more pain
Muangman, 2006 RCT 1 50 Compare pain with SSD versus Acticoat SSD leads to more pain
Huang, 2007 RCT 1 98 Compare epithelialization with SSD versus Acticoat SSD leads to slower epithelialization
Caruso, 2006 RCT 1 84 Compare epithelialization and cost with SSD versus Aquacel Ag SSD leads to slower epithelialization and higher cost
Muangman, 2010 RCT 1 70 Compare epithelialization and cost with SSD versus Aquacel Ag SSD leads to slower epithelialization and higher cost
Barret, 2000 RCT 1 20 Compare epithelialization, hospital length of stay and cost with SSD versus Biobrane SSD leads to slower epithelialization, longer hospital stay, and higher cost
Gerding, 1988 RCT 1 30 Compare epithelialization, number of dressing changes and cost with SSD versus Biobrane SSD leads to slower epithelialization, more dressing changes, and higher cost
Bugmann, 1998 RCT 1 76 Compare epithelialization and number of dressing changes SSD versus Mepitel SSD leads to slower epithelialization and more dressing changes
Subrahmanyam, 1998 RCT 1 50 Compare epithelialization with honey versus SSD Honey achieves faster epithelialization than SSD
Shahzad, 2013 RCT 1 50 Compare epithelialization and pain with aloe vera versus SSD Aloe vera achieves faster epithelialization and less pain than SSD
Silverstein, 2011 RCT 1 101 Compare epithelizaliation, pain and cost with Mepilex Ag versus SSD Mepilex Ag achieves faster epithelialization, less pain, and less cost than SSD
Yarboro, 2013 RCT 1 24 Compare epithelialization with Aquacel Ag versus SSD Aquacel Ag achieves less pain and requires fewer dressing changes
Adhya, 2015 RCT 1 54 Compare epithelialization with nanocrystalline silver-containing hydrogel versus SSD Burn epithelialization is faster with nanocrystalline silver-containing hydrogel than with SSD
Gee Kee, 2015 RCT 1 96 Compare epithelialization with Mepilex Ag versus Acticoat Acticoat has slower healing and more pain compared to Mepilex Ag
Genuino, 2014 RCT 1 50 Compare epithelialization with SSD versus petrolatum Petrolatum leads to faster epithelialization than SSD
Godhi, 2017 RCT 1 60 Compare epithelialization with SSD versus sucralfate Sucralfate leads to faster epithelialization than SSD
Brown, 2016 RCT 1 89 Compare epithelialization with Aquacel Ag versus Acticoat No difference in epithelialization or infection between Aquacel Ag and Acticoat
Vloemans, 2014 Systematic review 1 266 Compare epithelialization, pain and length of hospital stay with SSD versus Biobrane Biobrane achieves faster epithelialization, shorter length of stay, and less pain than SSD
Wasiak, 2013 Systematic review 1 1,307 Compare epithelialization and infection with various burn dressings SSD has the worst epithelialization and infection outcomes in burns
Heyneman, 2016 Systematic review 1 - Compare epithelialization with SSD versus nanocrystalline silver Nanocrystalline silver dressings lead to faster epithelialization than SSD
Gravante, 2009 Systematic review 1 285 Compare infection and pain with SSD versus nanocrystalline silver Nanocrystalline silver leads to less infection and pain than SSD
Aziz, 2017 Systematic review 1 717 Compare epithelialization and infection with honey versus SSD Honey results in faster epithelialization and less infection than SSD
Vieira, 2018 Review - - Evaluate the effectiveness of incisional NPWT in high-risk incisions Incisional NPWT improves wound outcomes
Abboud, 2016 RCT 1 110 Compare pain with Silverlon versus Gauze Silverlon reduces pain
Biffi, 2014 RCT 1 112 Compare infection with Aquacel Ag versus Gauze Aquacel Ag does not decrease infection compared to gauze
Newman, 2019 RCT 1 160 Compare wound complications with incisional NPWT versus silver dressing Incisional NPWT decreases wound complications compared to silver dressings
Ozaki, 2015 RCT 1 500 Compare infection with Acticoat versus Gauze Acticoat does not reduce infection rates
Ruiz-Tovar, 2015 RCT 1 147 Compare infection with silver-containing dressing versus mupirocin versus gauze Silver-containing dressings have more infections than mupirocin ointment
Dumville, 2016 Systematic Review 1 5,718 Compare infection with silver-containing dressings versus standard dressings Silver-containing dressings do not reduce infection rates
Li, 2017 Systematic review 1 2,196 Compare infection with silver-containing dressings versus standard dressings Silver-containing dressings do not reduce infection rates
Abbreviations: MRSA, Methicillin-resistant
Staphylococcus aureus; NPWT, Negative-pressure wound therapy; RCT, Randomized control trial; SSD, Silver sulfadiazine

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RESULTS

Quality of the Evidence

We found a total of 490 published studies using our PubMed searches. Four hundred and thirty-one articles were excluded for the following reasons: 149 were not relevant to our topic, 31 were not in English, 34 were duplicate articles across searches, and 196 did not have a nonsilver comparison group. We were thus left with 59 relevant studies. This included 8 basic science or animal studies (no level of evidence), 33 randomized-controlled trials (level 1 evidence), 1 retrospective study (level 3 evidence), 1 case series (level 4 evidence), 14 systematic reviews of randomized-controlled trials (level 1 evidence), and 2 qualitative review articles (no level of evidence).

Most prior reviews found that the quality of the published data on the use of silver in wound care is poor.8,9 This is due to the fact that these studies use inconsistent, and sometimes subjective, outcomes measures, such as pain with dressing change, days until reepithelialization, number of dressing changes until reepithelialization, wound size reduction at various time points, presence of infection, etc. In addition, many of the published studies are funded,10,11 or even written, by manufacturers of silver-containing dressings.12

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Silver Formulations, Effectiveness, and Toxicity

While the silver ion is a very powerful bactericidal agent, it also has toxic systemic and local effects. The systemic toxic effects are due to silver absorption through the wound, leading to argyria, which manifests as irreversible gray skin discoloration and loss of night vision.13–15 However, systemic toxicity is rare because serum silver is rapidly excreted in urine and feces.14

The local toxic effects of silver are more likely to occur, and are due to the cytotoxicity of the silver ion against keratinocytes and fibroblasts. Poon et al found that in monolayer cultures of keratinocytes and fibroblasts, silver became toxic to cells at a concentration of 33 ppm or greater.16 However, when fibroblasts were cultured in a collagen lattice, replicating more closely in vivo conditions, the toxic concentration increased to 60 ppm. On the other hand, for the silver ion to have effective bactericidal activity, a concentration of 30 to 40 ppm is needed.1

Therefore, the ideal silver-containing dressing would maintain a sustained (several days), therapeutic (≥30 ppm) silver ion concentration in the wound without causing systemic or local (≤60 ppm) silver toxicity.

SSD contains silver, glycols, alcohols, and sulfadiazine (an antibiotic).1 SSD has been found to release an extremely high initial silver concentration into the wound (up to 3,176 ppm),17 which rapidly decreases to below therapeutic levels. SSD can therefore have high local toxicity, without providing the sustained silver levels necessary for microbicidal activity. In addition, propylene glycol, which is part of the SSD formulation, is known to cause bone marrow toxicity and leukopenia.5,18

Newer dressings contain silver in a nanocrystalline state and elute silver into the wound in a sustained fashion, maintaining a concentration of up to 70 ppm for several days (slightly above the toxic threshold for keratinocytes and fibroblasts).16 These newer formulations include Silverlon (silver-coated nylon, Argentum Medical, Geneva, Ill.), Acticoat (silver-coated polyethylene, Smith & Nephew, London, UK), Mepilex Ag (silver-coated foam, Mölnlycke Healthcare, Norcross, Ga.), Mepitel Ag (silver-coated silicone, Mölnlycke Healthcare, Norcross, Ga.), Aquacel Ag (silver-coated cellulose hydrofiber, ConvaTec, Reading, UK), Promogran Prisma Ag (KCI, San Antonio, Tex.), and V.A.C. GranuFoam Silver (silver-coated polyurethane sponge, KCI, San Antonio, Tex.), amongst others. There are advantages and disadvantages to each of these formulations: Acticoat tends to adhere to the wound bed and can be painful upon removal,19 unlike Mepitel Ag and Mepilex Ag, both of which have a silicone interface, allowing them to adhere to the surrounding normal skin, but not to the wound itself (Table 2).19 Promogran Prisma contains collagen, which acts as a sacrificial substrate for matrix metalloproteinases, enhancing wound healing.20,21 The silver-coated polyurethane negative-pressure wound therapy (NPWT) sponge combines the advantages of NPWT with a sustained release of 20 to 40 ppm of silver,22,23 which is below the toxic threshold to keratinocytes and fibroblasts.

Table 2. - Commonly Used Dressings Containing Nanocrystalline Silver
Product Manufacturer Composition Properties
Silverlon Argentum Medical, Geneva, Ill. Silver-coated nylon Highest silver concentration
Acticoat Smith & Nephew, London, UK Silver-coated polyethylene Can adhere to the wound bed, causing pain with removal
Mepilex Ag Mölnlycke Healthcare, Norcross, Ga. Silver-coated foam with silicone interface Adheres to normal skin and not to wound bed
Mepitel Ag Mölnlycke Healthcare, Norcross, Ga. Silver-coated silicone Adheres to normal skin and not to wound bed
Aquacel Ag ConvaTec, Reading, UK Silver-coated cellulose hydrofiber Absorbs exudate
Promogran Prisma Ag KCI, San Antonio, Tex. Oxidized regenerated cellulose, collagen, and silver Contains collage, which acts as a sacrificial substrate
V.A.C. GranuFoam Silver KCI, San Antonio, Tex. Silver-coated polyurethane sponge Combines advantages of NPWT and silver

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Infected Open Wounds

Wound infection in the form of planktonic organisms or biofilm is known to impair wound healing. Foreign microorganisms in an open wound deplete local micronutrients and oxygen, and produce toxins that impair healing mechanisms.24 Therefore, eradicating infection is a prerequisite to obtaining a healed wound.

Biofilm is especially difficult to treat, because it enhances bacterial recalcitrance to antimicrobials. This is due to molecules within the extracellular polymeric substance of the biofilm that interfere with antibiotic function25 or physically shield the bacteria.26 One strategy to combat biofilm and jumpstart healing is by disrupting the biofilm and displacing the bacteria into a planktonic (rather than sessile) state, where they are more susceptible to systemic antibiotics. This can be achieved with sharp debridement of the wound. However, even with adequate debridement, even a few remaining bacteria can recreate the biofilm within 48 hours.27

A combination of surgical debridement and long-acting topical antimicrobials has been used as an effective method to combat biofilm.28 The ideal topical antimicrobial agent should be nontoxic to host tissue, have a broad antimicrobial spectrum, and maintain sustained levels in the wound until all infection is eradicated.

Nanocrystalline silver satisfies the above requirements. Several randomized-controlled trials and systematic reviews have demonstrated that dressings that contain nanocrystalline silver are beneficial for wounds that have high bacterial counts and bad odor.29,30 Silver-containing dressings also have the advantage of requiring less frequent dressing changes than non-silver-containing dressings, leading to lower pain levels.31

NPWT has been shown to decrease bacterial counts and accelerate healing in contaminated wounds.32,33 The addition of silver to the sponge plays a synergistic role with NPWT. The use of silver-coated polyurethane sponges has been shown to reduce bacterial counts of biofilm-causing organisms, such as Pseudomonas aeruginosa and Staphylococcus aureus,34,35 including MRSA,36 more than plain polyurethane sponges, leading to faster healing in infected diabetic foot ulcers.37 The synergistic effects of silver and NPWT can be achieved by using a silver-coated polyurethane sponge or by adding a silver layer under a plain polyurethane sponge.38

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Noninfected Open Wounds

In contrast, there is very little evidence in favor of silver for noninfected wounds. Multiple meta-analyses and randomized-controlled trials found that nanocrystalline silver-containing dressings were no more effective than gauze for lower-extremity ulcers,8,39–41 chronic noninfected wounds,42 and pressure ulcers.9,43 In fact, for noninfected, open wounds, silver-containing dressings have been found to increase cost40 and delay epithelialization. In an animal study of clean burns, Mepilex Ag had slower healing than triple antibiotic ointment.44 For skin graft donor sites, Acticoat has been found to delay epithelialization by more than 50% when compared to occlusive dressings.45 As mentioned above, dressings containing nanocrystalline silver lead to silver ion concentrations in the wound of up to 70 ppm, which is above the toxic threshold for keratinocytes and fibroblasts.16

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Burns

Even though SSD is widely used for the treatment of second-degree burns,46 it has been shown to have some of the worst outcomes in burn treatment, in terms of infection and epithelialization.47,48 It is less effective than aloe vera,49,50 sucralfate,51 petrolatum gel,52 honey,53–58,85,86 and Biobrane (nylon, silicone and collagen composite, Smith & Nephew, London, UK).59–62 In addition to slowing epithelialization, SSD has been shown to increase the rate of hypertrophic scar formation.63

In contrast, dressings containing nanocrystalline silver have been found to be superior to SSD and to silver-free dressings for burns, in terms of epithelialization, infection, pain, and cost.18,64–73 In addition, dressings containing nanocrystalline silver significantly reduce the cost of care when compared to SSD.57,61,62,66,70,71,73 In an animal study examining several dressings for burns, Selcuk et al found that the most effective dressing against Acinetobacter baumannii was Acticoat, followed by octenidine, then mupirocin, with SSD being the least effective dressing.74 Brown et al found that Aquacel Ag and Acticoat were equivalent for burn healing.75

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Closed Surgical Incisions

One study found that the use of Silverlon as a dressing over closed surgical incisions resulted in less pain.2 However, there is no evidence that the use of a silver-containing dressing to cover a closed surgical incision reduces infection or accelerates healing. This has been demonstrated in numerous randomized-controlled trials examining both clean and clean-contaminated operations.76–80 One surgical dressing that has been shown to reduce infection, wound healing complications, and reoperation is incisional NPWT, such as Prevena (Silver-impregnated foam, KCI, San Antonio, Tex.) or plain polyurethane foam with an NPWT machine.81 Multiple studies have demonstrated the effectiveness of incisional NPWT in high-risk incisions.82–84 Incisional NPWT is effective regardless of whether a plain polyurethane sponge or a silver-coated polyurethane sponge is used.85

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Alternatives to Silver

There are several silver-free antimicrobial topical wound treatments that have been shown to be effective. Some of these dressings are widely used in Europe, but not in the United States.

Octenidine dihydrochloride (OCT) is a surfactant that can be used as a topical antimicrobial with a very broad spectrum. It has been shown to be less toxic to keratinocytes and fibroblasts than silver, leading to faster wound healing.86 Polihexanide (PHMB) is also an antimicrobial with a very broad spectrum, which has been shown to have superior efficacy as a wound washing agent when compared to normal saline.87 There is no resistance to either OCT or PHMB, and both have strong activity against MRSA, VRE, and Candida albicans.3 Both OCT and PHMB have been used successfully as instillation solutions for NPWT in heavily contaminated wounds.3

Finally, medical-grade honey has been shown to be a valuable option for wound management. Honey has a low pH and generates a low, sustained concentration of hydrogen peroxide, which gives it broad antimicrobial activity against both Gram-positive and Gram-negative organisms, without toxic effects on tissue.88 Honey leads to faster burn epithelialization than SSD.89

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DISCUSSION

Our qualitative literature review on silver has limitations: it is not a quantitative systematic review. This is due to the heterogeneity of the outcome measures in the published literature, which makes it difficult to pool data and generate meaningful conclusions. However, from our qualitative analysis, we can provide the following strategies for the proper use of silver in wound care:

  • 1) SSD slows healing, and should be avoided in wound care, including in burn treatment. In addition, it should not be used as the gold standard for burn research.
  • 2) In infected wounds, dressings containing nanocrystalline silver are helpful in the early treatment phase (first 2–3 weeks) to reduce bacterial counts and mitigate wound odor. It is best used as an adjunct to surgical debridement. As the wound becomes cleaner, silver-free dressings should be used to minimize toxicity towards keratinocytes and fibroblasts.90 Silver-containing dressings should not be used long-term.3,10
  • 3) During the early phase of treatment, NPWT with a silver sponge is especially useful, because it combines the advantages of NPWT with the antimicrobial properties of silver. In addition, the silver ion concentration produced is in the wound is 20 to 40 ppm, which is bactericidal, but lower than the toxic threshold to keratinocytes and fibroblasts.16,22,23
  • 4) In clean wounds, there is no role for the use of silver-containing dressings, as these can delay epithelialization. As discussed above, these dressings elute silver ion up to a concentration of 70 ppm, which is within the toxic range for keratinocytes and fibroblasts.
  • 5) Silver-containing dressings have not been shown to decrease the risk of infection when used over closed surgical incisions. One study found decreased pain when silver-containing dressings were used over a closed incision. For high-risk closed surgical incisions (in patients who smoke, who have diabetes, etc.), the use of incisional NPWT with a plain polyurethane sponge lowers the risk of wound healing complications.
  • 6) Alternatively, lesser known topical wound treatments, such octenidine and polyhexanide, may produce good outcomes, especially when used as instillation solutions for NPWT.
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CONCLUSIONs

The judicious and selective use of silver in wound care in the correct situation can help accelerate healing, primarily as an adjunct to surgical debridement in infected wounds. Silver-containing dressings, especially nanocrystalline silver, are most useful in infected wounds, but do not provide added benefit in clean, noninfected wounds, and may slow the healing of those wounds. Moreover, silver-containing dressings do not confer an added advantage when applied over closed surgical incisions. In burns, dressings containing nanocrystalline silver are beneficial, but SSD leads to slower epithelialization, higher cost, more infections, and more pain. Plastic surgeons must be familiar with these nuances to optimize patient outcomes.

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REFERENCES

1. Murphy PS, Evans GR. Advances in wound healing: a review of current wound healing products. Plast Surg Int. 2012;2012:190436.
2. Abboud EC, Legare TB, Settle JC, et al. Do silver-based wound dressings reduce pain? A prospective study and review of the literature. Burns. 2014;40(suppl 1):S40–S47.
3. Kramer A, Dissemond J, Kim S, et al. Consensus on wound antisepsis: update 2018. Skin Pharmacol Physiol. 2018;31:28–58.
4. Khundkar R, Malic C, Burge T. Use of acticoat dressings in burns: what is the evidence? Burns. 2010;36:751–758.
5. Atiyeh BS, Costagliola M, Hayek SN, et al. Effect of silver on burn wound infection control and healing: review of the literature. Burns. 2007;33:139–148.
6. Silver S. Bacterial silver resistance: molecular biology and uses and misuses of silver compounds. FEMS Microbiol Rev. 2003;27:341–353.
7. McHugh GL, Moellering RC, Hopkins CC, et al. Salmonella typhimurium resistant to silver nitrate, chloramphenicol, and ampicillin. Lancet. 1975;1:235–240.
8. Chambers H, Dumville JC, Cullum N. Silver treatments for leg ulcers: a systematic review. Wound Repair Regen. 2007;15:165–173.
9. Dumville JC, Keogh SJ, Liu Z, et al. Alginate dressings for treating pressure ulcers. Cochrane Database Syst Rev. 2015:CD011277.
10. Dissemond J, Böttrich JG, Braunwarth H, et al. Evidence for silver in wound care - meta-analysis of clinical studies from 2000-2015. J Dtsch Dermatol Ges. 2017;15:524–535.
11. Woo KY, Coutts PM, Sibbald RG. A randomized controlled trial to evaluate an antimicrobial dressing with silver alginate powder for the management of chronic wounds exhibiting signs of critical colonization. Adv Skin Wound Care. 2012;25:503–508.
12. Nherera L, Trueman P, Roberts C, et al. Silver delivery approaches in the management of partial thickness burns: a systematic review and indirect treatment comparison. Wound Repair Regen. 2017;25:707–721.
13. Drake PL, Hazelwood KJ. Exposure-related health effects of silver and silver compounds: a review. Ann Occup Hyg. 2005;49:575–585.
14. Lansdown AB. Critical observations on the neurotoxicity of silver. Crit Rev Toxicol. 2007;37:237–250.
15. Lansdown AB. A pharmacological and toxicological profile of silver as an antimicrobial agent in medical devices. Adv Pharmacol Sci. 2010;2010:910686.
16. Poon VK, Burd A. In vitro cytotoxity of silver: implication for clinical wound care. Burns. 2004;30:140–147.
17. Warriner R, Burrell R. Infection and the chronic wound: a focus on silver. Adv Skin Wound Care. 2005;18(suppl 1):2–12.
18. Adhya A, Bain J, Ray O, et al. Healing of burn wounds by topical treatment: a randomized controlled comparison between silver sulfadiazine and nano-crystalline silver. J Basic Clin Pharm. 2014;6:29–34.
19. Gee Kee EL, Kimble RM, Cuttle L, et al. Randomized controlled trial of three burns dressings for partial thickness burns in children. Burns. 2015;41:946–955.
20. Cullen B, Lázaro Martínez JL. Underlying biochemistry in non-healing wounds perpetuates chronicity. Wounds Int 2016;7:10–16.
21. Applewhite A, Chowdhry SA, Desvigne M, et al. Inpatient and outpatient wound treatment recommendations: assessing use of negative pressure wound therapy systems or oxidized regenerated cellulose (ORC)/ collagen/silver-ORC dressings. Wounds. 2018;30(suppl 8):S19–S35.
22. Abarca-Buis RF, Munguía NM, Gonzalez JM, et al. Silver from polyurethane dressing is delivered by gradient to exudate, tissue, and serum of patients undergoing negative-pressure wound treatment. Adv Skin Wound Care. 2014;27:156–162.
23. Sachsenmaier S, Peschel A, Ipach I, et al. Antibacterial potency of V.A.C. Granufoam silver(®) dressing. Injury. 2013;44:1363–1367.
24. Stanirowski PJ, Wnuk A, Cendrowski K, et al. Growth factors, silver dressings and negative pressure wound therapy in the management of hard-to-heal postoperative wounds in obstetrics and gynecology: a review. Arch Gynecol Obstet. 2015;292:757–775.
25. Chiang WC, Nilsson M, Jensen PØ, et al. Extracellular DNA shields against aminoglycosides in pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother. 2013;57:2352–2361.
26. Billings N, Millan M, Caldara M, et al. The extracellular matrix component psl provides fast-acting antibiotic defense in pseudomonas aeruginosa biofilms. Plos Pathog. 2013;9:e1003526.
27. Roy S, Elgharably H, Sinha M, et al. Mixed-species biofilm compromises wound healing by disrupting epidermal barrier function. J Pathol. 2014;233:331–343.
28. Barker JC, Khansa I, Gordillo GM. A formidable foe is sabotaging your results: what you should know about biofilms and wound healing. Plast Reconstr Surg. 2017;139:1184e–1194e.
29. Medical Advisory Secretariat. Management of chronic pressure ulcers: an evidence-based analysis. Ont Health Technol Assess Ser 2009;9:1–203.
30. Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database Syst Rev 2007:CD005486.
31. Meekul J, Chotirosniramit A, Himakalasa W, et al. A randomized controlled trial on the outcome in comparing an alginate silver dressing with a conventional treatment of a necrotizing fasciitis wound. Int J Low Extrem Wounds. 2017;16:108–113.
32. Morykwas MJ, Argenta LC, Shelton-Brown EI, et al. Vacuum-assisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997;38:553–562.
33. Armstrong DG, Lavery LA; Diabetic Foot Study Consortium. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial. Lancet. 2005;366:1704–1710.
34. Stinner DJ, Waterman SM, Masini BD, et al. Silver dressings augment the ability of negative pressure wound therapy to reduce bacteria in a contaminated open fracture model. J Trauma. 2011;71(suppl 1):S147–S150.
35. Ngo QD, Vickery K, Deva AK. The effect of topical negative pressure on wound biofilms using an in vitro wound model. Wound Repair Regen. 2012;20:83–90.
36. Ellenrieder M, Redanz S, Bader R, et al. Influence of antimicrobial coatings of vacuum-assisted closure dressings on methicillin-resistant staphylococcus aureus growth kinetics: an in vitro study. Surg Infect (Larchmt). 2015;16:139–145.
37. Günal Ö, Tuncel U, Turan A, et al. The use of vacuum-assisted closure and granufoam silver® dressing in the management of diabetic foot ulcer. Surg Infect (Larchmt). 2015;16:558–565.
38. Karr JC, de Mola FL, Pham T, et al. Wound healing and cost-saving benefits of combining negative-pressure wound therapy with silver. Adv Skin Wound Care. 2013;26:562–565.
39. O’Meara S, Al-Kurdi D, Ologun Y, et al. Antibiotics and antiseptics for venous leg ulcers. Cochrane Database Syst Rev. 2014:CD003557.
40. Michaels JA, Campbell B, King B, et al. Randomized controlled trial and cost-effectiveness analysis of silver-donating antimicrobial dressings for venous leg ulcers (VULCAN trial). Br J Surg. 2009;96:1147–1156.
41. Bergin S, Wraight P. Silver based wound dressings and topical agents for treating diabetic foot ulcers. Cochrane Database Syst Rev. 2006:CD005082.
42. Storm-Versloot MN, Vos CG, Ubbink DT, Vermeulen H. Topical silver for preventing wound infection. Cochrane Database Syst Rev. 2010:CD006478.
43. Norman G, Dumville JC, Goto S, et al. Antibiotics and antiseptics for pressure ulcers. Cochrane Database Syst Rev. 2016:CD011586.
44. Toussaint J, Chung WT, Osman N, et al. Topical antibiotic ointment versus silver-containing foam dressing for second-degree burns in swine. Acad Emerg Med. 2015;22:927–933.
45. Innes ME, Umraw N, Fish JS, et al. The use of silver coated dressings on donor site wounds: a prospective, controlled matched pair study. Burns. 2001;27:621–627.
46. Oen IM, van Baar ME, Middelkoop E, et al.; Facial Burns Group. Effectiveness of cerium nitrate-silver sulfadiazine in the treatment of facial burns: a multicenter, randomized, controlled trial. Plast Reconstr Surg. 2012;130:274e–283e.
47. Heyneman A, Hoeksema H, Vandekerckhove D, et al. The role of silver sulphadiazine in the conservative treatment of partial thickness burn wounds: a systematic review. Burns. 2016;42:1377–1386.
48. Wasiak J, Cleland H, Campbell F, Spinks A. Dressings for superficial and partial thickness burns. Cochrane Database Syst Rev. 2013:CD002106.
49. Shahzad MN, Ahmed N. Effectiveness of aloe vera gel compared with 1% silver sulphadiazine cream as burn wound dressing in second degree burns. J Pak Med Assoc. 2013;63:225–230.
50. Khorasani G, Hosseinimehr SJ, Azadbakht M, et al. Aloe versus silver sulfadiazine creams for second-degree burns: a randomized controlled study. Surg Today. 2009;39:587–591.
51. Godhi AS, Ram P, Powar R. Efficacy of topical sucralfate versus silver sulfadiazine in the management of burns: a 1-year randomized controlled trial. J West Afr Coll Surg. 2017;7:57–70.
52. Genuino GA, Baluyut-Angeles KV, Espiritu AP, et al. Topical petrolatum gel alone versus topical silver sulfadiazine with standard gauze dressings for the treatment of superficial partial thickness burns in adults: a randomized controlled trial. Burns. 2014;40:1267–1273.
53. Aziz Z, Abdul Rasool Hassan B. The effects of honey compared to silver sulfadiazine for the treatment of burns: a systematic review of randomized controlled trials. Burns. 2017;43:50–57.
54. Baghel PS, Shukla S, Mathur RK, et al. A comparative study to evaluate the effect of honey dressing and silver sulfadiazene dressing on wound healing in burn patients. Indian J Plast Surg. 2009;42:176–181.
55. Shah H, Naeemullah Khan M, Khan K, et al. Effectiveness of honey dressing and silver sulfadiazine dressing on wounds healing in burn patients. J Biosci Med. 2013;3:23–8
56. Sami AN, Mehmood N, Qureshi MA, et al. Honey compared with silver sulphadiazine as burn wound dressing. Ann Pak Inst Med Sci. 2011;7: 22–25.
57. Mujalde VS, Jalaj A, Pipariya PR. To assess the efficacy of honey in comparison with 1% silver sulfadiazine cream as a burn wound dressing in superficial and partial thickness of burns. Sch J App Med Sci. 2014;2(1B):193–196
58. Mashhood AA, Khan TA, Sami AN. Honey compared with 1% silver sulfadiazine cream in the treatment of superficial and partial thickness burns. J Pak Assoc Derma. 2006;16:14–19.
59. Vloemans AF, Hermans MH, van der Wal MB, et al. Optimal treatment of partial thickness burns in children: a systematic review. Burns. 2014;40:177–190.
60. Lal S, Barrow RE, Wolf SE, et al. Biobrane improves wound healing in burned children without increased risk of infection. Shock. 2000;14:314–318; discussion 318.
61. Barret JP, Dziewulski P, Ramzy PI, et al. Biobrane versus 1% silver sulfadiazine in second-degree pediatric burns. Plast Reconstr Surg. 2000;105:62–65.
62. Gerding RL, Imbembo AL, Fratianne RB. Biosynthetic skin substitute vs. 1% silver sulfadiazine for treatment of inpatient partial-thickness thermal burns. J Trauma. 1988;28:1265–1269.
63. Qian LW, Fourcaudot AB, Leung KP. Silver sulfadiazine retards wound healing and increases hypertrophic scarring in a rabbit ear excisional wound model. J Burn Care Res. 2017;38:e418–e422.
64. Gravante G, Caruso R, Sorge R, et al. 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;63:201–205.
65. Yarboro DD. A comparative study of the dressings silver sulfadiazine and Aquacel Ag in the management of superficial partial-thickness burns. Adv Skin Wound Care. 2013;26:259–262.
66. Silverstein P, Heimbach D, Meites H, et al. An open, parallel, randomized, comparative, multicenter study to evaluate the cost-effectiveness, performance, tolerance, and safety of a silver-containing soft silicone foam dressing (intervention) vs silver sulfadiazine cream. J Burn Care Res. 2011;32:617–626.
67. Varas RP, O’Keeffe T, Namias N, et al. A prospective, randomized trial of acticoat versus silver sulfadiazine in the treatment of partial-thickness burns: which method is less painful? J Burn Care Rehabil. 2005;26:344–347.
68. Muangman P, Chuntrasakul C, Silthram S, et al. Comparison of efficacy of 1% silver sulfadiazine and acticoat for treatment of partial-thickness burn wounds. J Med Assoc Thai. 2006;89:953–958.
69. Huang Y, Li X, Liao Z, et al. A randomized comparative trial between acticoat and SD-ag in the treatment of residual burn wounds, including safety analysis. Burns. 2007;33:161–166.
70. Caruso DM, Foster KN, Blome-Eberwein SA, et al. Randomized clinical study of hydrofiber dressing with silver or silver sulfadiazine in the management of partial-thickness burns. J Burn Care Res. 2006;27:298–309.
71. Muangman P, Pundee C, Opasanon S, et al. A prospective, randomized trial of silver containing hydrofiber dressing versus 1% silver sulfadiazine for the treatment of partial thickness burns. Int Wound J. 2010;7:271–276.
72. Bugmann P, Taylor S, Gyger D, et al. A silicone-coated nylon dressing reduces healing time in burned paediatric patients in comparison with standard sulfadiazine treatment: a prospective randomized trial. Burns. 1998;24:609–612.
73. Gotschall CS, Morrison MI, Eichelberger MR. Prospective, randomized study of the efficacy of mepitel on children with partial-thickness scalds. J Burn Care Rehabil. 1998;19:279–283.
74. Selçuk CT, Durgun M, Ozalp B, et al. Comparison of the antibacterial effect of silver sulfadiazine 1%, mupirocin 2%, acticoat and octenidine dihydrochloride in a full-thickness rat burn model contaminated with multi drug resistant acinetobacter baumannii. Burns. 2012;38:1204–1209.
75. Brown M, Dalziel SR, Herd E, et al. A randomized controlled study of silver-based burns dressing in a pediatric emergency department. J Burn Care Res. 2016;37:e340–e347.
76. Biffi R, Fattori L, Bertani E, et al. Surgical site infections following colorectal cancer surgery: a randomized prospective trial comparing common and advanced antimicrobial dressing containing ionic silver. World J Surg Oncol. 2012;10:94.
77. Dumville JC, Gray TA, Blazeby J, et al. Dressings for the prevention of surgical site infection. Cochrane Database Syst Rev. 2016:CD003091.
78. Li HZ, Zhang L, Chen JX, et al. Silver-containing dressing for surgical site infection in clean and clean-contaminated operations: a systematic review and meta-analysis of randomized controlled trials. J Surg Res. 2017;215:98–107.
79. Ozaki CK, Hamdan AD, Barshes NR, et al. Prospective, randomized, multi-institutional clinical trial of a silver alginate dressing to reduce lower extremity vascular surgery wound complications. J Vasc Surg. 2015;61:419–427.e1.
80. Ruiz-Tovar J, Llavero C, Morales V, et al. Total occlusive ionic silver-containing dressing vs mupirocin ointment application vs conventional dressing in elective colorectal surgery: effect on incisional surgical site infection. J Am Coll Surg. 2015;221:424–429.
81. Newman JM, Siqueira MBP, Klika AK, et al. Use of closed incisional negative pressure wound therapy after revision total hip and knee arthroplasty in patients at high risk for infection: a prospective, randomized clinical trial. J Arthroplasty. 2019;34:554–559.e1.
82. Kwon J, Staley C, McCullough M, et al. A randomized clinical trial evaluating negative pressure therapy to decrease vascular groin incision complications. J Vasc Surg. 2018;68:1744–1752.
83. Curran T, Alvarez D, Nagle D, et al. Prophylactic closed-incision negative-pressure wound therapy is associated with decreased surgical site infection in high-risk colorectal surgery laparotomy wounds. Colorectal Dis 2019;21:110–118.
84. Abatangelo S, Saporiti E, Giatsidis G. Closed incision negative-pressure therapy (cinpt) reduces minor local complications in post-bariatric abdominoplasty body contouring: a retrospective case-control series. Obes Surg. 2018;28:2096–2104.
85. Vieira ALG, Stocco JGD, Ribeiro ACG, et al. Dressings used to prevent surgical site infection in the postoperative period of cardiac surgery: integrative review. Rev Esc Enferm USP. 2018;52:e03393.
86. Krasowski G, Jawień A, Tukiendorf A, et al. A comparison of an antibacterial sandwich dressing vs dressing containing silver. Wound Repair Regen. 2015;23:525–530.
87. Bellingeri A, Falciani F, Traspedini P, et al. Effect of a wound cleansing solution on wound bed preparation and inflammation in chronic wounds: a single-blind RCT. J Wound Care. 2016;25:160, 162–166, 168.
88. Subrahmanyam M. Topical application of honey in treatment of burns. Br J Surg. 1991;78:497–498.
89. Subrahmanyam M. A prospective randomised clinical and histological study of superficial burn wound healing with honey and silver sulfadiazine. Burns. 1998;24:157–161.
90. Lazareth I, Meaume S, Sigal-Grinberg ML, et al. Efficacy of a silver lipidocolloid dressing on heavily colonised wounds: a republished RCT. J Wound Care. 2012;21:96–102.
Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.