A Scoping Review of the Use of Silver-impregnated Dressings for the Treatment of Chronic Wounds
Topical silver agents and dressings are used to control infection and promote healing in chronic wounds, but reviews published from 2006 to 2011 found heterogeneous results regarding their effectiveness. A scoping review was conducted to examine the extent, range, and nature of research activity surrounding chronic wound care that employed silver-impregnated dressings; identify research gaps in the existing literature; and summarize the evidence to provide recommendations for future clinical studies.
Ten (10) electronic databases and additional sources were screened from their inception to May 2016; search terms for the different databases included but were not limited to silver, chronic, complications, wound, ulcer, and sore. English-language articles that compared silver dressings with an alternate treatment in adults with chronic wounds and that reported clinical outcome measures were included. Of 222 full-text reviewed studies, 27 were included for qualitative analysis. Qualitative analysis was guided by key findings identified among the included studies that were analyzed in aggregate form where appropriate. In comparative analyses of the 26 studies that investigated wound healing, 15 revealed significantly positive wound healing outcomes with silver treatments versus 9 that did not; the remaining 2 failed to provide statistical values of significance. Of 17 studies that presented data on microbiology, 3 reported significant microbial load improvement for silver dressings, 9 noted nonsignificant findings, and 4 provided no statistical values. Pain, adverse events, and treatment cost were included in 5, 7, and 3 studies, respectively, with heterogeneous findings. The heterogeneous evidence regarding the impact of silver dressings on clinical outcomes may be related to differences in the silver treatments themselves, heterogeneous intervention strategies, study designs, outcomes, and measures. Well-designed clinical studies with multiple outcome parameters are necessary to determine the optimal type and use of silver-dressings in chronic wounds.
An aging population has been associated with an increased incidence of major chronic diseases, including the development of chronic wounds.1 Despite having multiple definitions, a chronic wound can be described as a wound that has not healed completely after 6 weeks or as having a limited response to treatment change during that time.2 Chronic wounds include diabetic ulcers, pressure ulcers, venous ulcers, arterial ulcers, infected surgical or traumatic wounds, and wounds related to vasculitis and immunosuppressive therapy that have not healed with standard care.3-7 Chronic wounds may be painful and also lead to complications such as septicemia, hospitalization, and amputation.8
Silver is used in clinical practice as a therapeutic wound care agent in topical treatments, solutions, or dressings. Silver-based dressings may take the form of foams, hydrofibers, gels, alginates, hydrocolloids, films, and collagen products. To date, Health Canada has 23 active licenses for silver-containing dressings that incorporate either inorganic, nanoparticle, or nanocrystalline silver. According to reviews of the literature,9,10 dressings with a silver component provide a broad-spectrum antimicrobial agent that leads to bacterial cell death by damaging bacterial cell membranes and inhibiting replication by denaturing bacterial DNA and RNA.
A number of reviews, including several systematic reviews that focused on assessing the effect of silver-based therapies on various chronic wounds,9,11-16 reported heterogeneous findings. Three (3) reviews9,11,14 reported no significant differences in clinical outcomes between silver dressings and other types of dressings, whereas 4 reviews found positive effects of silver dressings such as decreased wound size,13,16 odor,12,13 and wound exudate12,13 and less frequent dressing changes, suggesting cost reductions.12,15 However, these reviews were conducted between 2006 and 2011 and included a limited number of studies ranging between 4 and 14 trials. A 2010 review16 that included additional studies found 28 out of 39 clinical studies showed statistically significant outcome parameters in support of silver. However, the aforementioned study evaluated a wide spectrum of wounds, including burn injuries; furthermore, clinical outcomes such as wound healing or bacterial load were not discussed in depth. Given that the use of silver dressings has increased over the last few years, an evaluation of recent evidence such as an indepth review regarding the effectiveness of silver dressings on chronic wounds was needed.
The present scoping review provides a preliminary assessment of the literature to identify research gaps without conducting a formal quality assessment of the studies included or meta-analysis, which is commonly included in systematic reviews. Therefore, the objective of this review was to examine the extent, range, and nature of research activity surrounding chronic wound care that employed silver-impregnated dressings, identify research gaps in the existing literature, and subsequently summarize the evidence to provide recommendations for future clinical studies.
Methods and Procedures
This scoping review was conducted as per the 5-stage framework of Arksey and O’Malley.17 The 5 stages reflect an iterative process and include 1) identifying an initial research question, 2) identifying relevant studies, 3) study selection, 4) charting of data, and 5) summarizing and reporting of results.17
The inclusion criteria for studies were as follows: 1) English-language articles of original research; 2) study population >18 years of age; 3) study population must have a chronic wound(s) (ie, venous, arterial, and mixed insufficiency ulcers; diabetic ulcers; pressure ulcers; pilonidal sinuses; and infected surgical wounds or wounds other than those mentioned that have been present >6 weeks); 4) the study design must have a comparison (including historical comparisons either within the same patients or between groups of patients) whereby silver-impregnated dressings or topical silver agents (used with dressings) are compared to any sham, silver, or nonsilver dressings for a chronic wound; and 5) the study must report on clinical outcome measures such as wound healing, microbiology, pain, adverse events, and cost. Exclusion criteria included 1) laboratory or animal studies, 2) letters to the editor, 3) case reports or series, 4) protocols, and 5) reviews. There was no restriction on study location or date of the trial.
A search strategy was developed in conjunction with a university health sciences librarian. Medical Subject Headings (MeSH), Boolean operators, truncation, and filters were used to develop a strategy to narrow or widen the search accordingly. The search strategies for the different databases included but were not limited to the following main search terms: silver, chronic, complications, wound, ulcer, and sore.
The following electronic databases were searched from their earliest record to May 2016: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the Cumulative Index of Nursing and Allied Health Literature, The Health Technology Assessment Database, The National Health Service Economic Evaluation Database, Database of Arabic Literature in Western Research (DAL), and IndMED. Wound-related electronic databases and websites also were searched from their earliest record to May 2016 and included The Cochrane Wounds Group Specialized Register, Canadian Association of Wound Care, European Wound Management Association, Wounds UK, World Union of Wound Healing Societies (WUWHS), and Worldwide Wounds. Reference lists of any retrieved reports and reviews were scrutinized for additional trials. The clinical trial registries of ClinicalTrials.gov and the World Health Organization (WHO) Trial Search Portal also were searched for relevant clinical trials. Google searching was limited to relevant domains using Google commands (eg, site:).
Article selection followed the Preferred Reporting of Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement19 (see Figure 1). One (1) author reviewed the screened articles by title and abstract for relevance. Full-text articles of relevant studies then were reviewed and eliminated if they did not meet the inclusion criteria. Any uncertainty about the inclusion of any article was discussed with other authors and resolved by consensus. References were exported to Endnote X7 (Clarivate Analytics, Philadelphia, PA) and duplicates were eliminated.
Data extraction and charting were guided by key findings of included studies. Charted information was tabulated and included year of publication, study design, population characteristics, description of comparator, details of the silver-impregnated dressing intervention, outcomes, measures, and key findings. No quality assessment of the included studies nor statistical analysis was performed due to the nature of the present review.17 The results of the original research articles are presented individually in a table format and discussed either individually (as warranted) and/or in aggregate form.
The search identified 1076 journal articles; 652 records remained after all duplicates were removed. Thereafter, the initial screening of titles and/or abstracts resulted in the exclusion of 430 citations, and 222 records were retained and reviewed. A second full-text screening was performed whereby 195 records were excluded and 27 full-text citations were included for this review. Figure 1 shows the PRISMA flow diagram, which depicts the article search and screening process.
The 27 studies included in this scoping review were comparative studies (as defined in the inclusion criteria) (see Table 1); of these, 26 were prospective randomized studies and 1 was a retrospective study. The number of participants in the studies ranged from 10 to 619, and all studies included participants who were 18 years of age or older (range 18–99 years). Studies included individuals with a chronic wound including pressure ulcers, diabetic foot ulcers, venous/arterial/mixed insufficiency ulcers, pilonidal ulcers, or wounds present for a period of at least 6 weeks. Silver-treatment regimens included a variety of silver dressings or topical creams (used with a dressing) produced by different manufacturers or impregnated with silver compound topical creams (1% silver sulfadiazine and silver zinc sulfadiazine). The comparator treatments varied substantially between the studies; they included a silver dressing or included another silver compound alongside an established treatment as a comparator treatment in 4 of the studies.
Among the included articles, 5 research studies18-22 involved trials in which both groups were provided a type of silver treatment; the other 22 studies included a comparison between a silver agent and a nonsilver agent. Conversely, 7 journal articles followed a mixed interventions approach, where either treatment (silver or comparator) used an additional type of treatment. Tables 2 through 5 summarize studies according to 4 specifications: silver versus silver (mixed interventions and single interventions) and silver versus nonsilver (mixed interventions and single interventions).
Number of study participants. The number of study participants greatly varied among the studies included in this scoping review (see Figure 2). The majority of studies (13) included a participant population range of 1 to 50 individuals.18,19,21-31 The second (n= 51–100)32-36 and third (n= 101–200)37-41 largest categories included 5 studies each. Among larger participant populations (>200 patients), 1 study20 had 201–300 participants, 2 had 301–400 participants,42,43 and 1 had >600 participants.44
Description of silver interventions. The studies examined the use of silver dressings produced by different manufacturers, with numerous different silver compositions. A total of 16 different silver dressings were used across the 27 studies. Table 6 presents both the composition and chemical names of the silver treatments assessed in the included studies. The most frequently used silver dressings were hydrofiber silver dressings,20,24,37,42 carboxymethyl cellulose contact layer silver dressings,20,24,39,42 and foam dressings with silver.24,40,42,44 Five (5) studies18,26,30,31,43 reported the use of a silver dressing with no composition or brand information provided. Dressings differed in terms of components such as padding conformation and the inclusion of secondary compounds. Five (5) studies18-22 used silver dressings in the treatment and control groups.
Outcome measures. Outcome measures varied among the studies and included wound size, complete/partial wound healing, rate of wound healing, presence of exudate leakage, exudate amount, bacterial load, average treatment duration, number of dressing changes required, pain, and adverse events. Various studies included baseline characteristics of wounds (wound size, wound volume, exudate amount, and so on) in order to allow for a more thorough comparison of wounds for silver versus comparator interventions. Wound size, complete healing, tissue type, bacterial load, exudate amount, pain status, infection rates, adverse effects, and treatment costs were the most frequently used outcome measures for testing the efficacy of a wound treatment.
Wound size. Wound size was the most investigated parameter among the included records (20 out of 27 studies)18-20,23,25,27,29-41,44; of these, 16 reported statistical values, among which 10 studies18-20,22,25,30,35-37,40 found nonsignificant differences between the silver product and the comparator group and 6 studies27,31,32,38,39,44 showed a significantly higher reduction of wound size area in patients pertaining to the silver treatment group. Four (4) studies23,33,34,41 did not report statistical values for the evaluated wound size/area parameters.
This specific outcome measure was evaluated in a number of ways. For example, some studies reported wound area size reduction as a percentage or in cm, whereas others set a baseline measurement (wounds that reached 24 cm2) in order to test for size reduction. Other studies evaluated reduction of wound volume (mm) and depth (cm). Of the 10 studies that did not report significant differences between groups, 7 found positive but nonsignificant wound area reduction data (in cm2, cm, and percent area) for the silver treatment, with P values ranging from .085 to .570.
Wound healing. Although outcome measures for healing were numerous, a standardized method for measuring healing was not apparent. Outcome measures included wound size reduction (number of wounds that decreased in size, percentage of wounds that decreased, percentage and cm of wound size/area reduction), healing rate/velocity, wound recurrence, clinical improvement/healing progression, wound closure, wound closure time, and changes in tissue types (granulation, macerated/red skin). Of the 26 studies that evaluated wound healing, 15 studies18,21,23-27,31,32,36,38-40,43,44 demonstrated statistical significance with regard to at least 1 wound healing outcome parameter, and 9 studies19,20,22,29,30,35,40,42 noted that the silver treatment did not have a significant effect on any of the evaluated healing parameters (P >.05) as compared to the control group. Two (2) studies33,41 did not report P values or confidence boundaries of estimates.
Two (2) studies18,19 evaluated the impact of the silver intervention on wound healing using the Pressure Ulcer Scale for Healing (PUSH) score,45 a compound measure of several proxy outcomes that uses a scoring system to determine healing progression. Specifically, the PUSH score measures wound size (scale 0 to 10, where 10 means the wound is >24 cm2), exudate amount (scale 0 to 3, where 3 is heavy exudate amount), and tissue type (scale 0 to 4, where 4 means the wound appears to have necrotic [dead] tissue). However, neither of these 2 studies reported their PUSH score reductions to be significantly different (P = .402 and P = .071, respectively) between the 2 study treatments.
Healing rate. Healing rate was used as an indicator of how fast (in terms of days or weeks) chronic wounds were able to heal during the intervention. Of the 11 studies20-22,26,29,34,36,37,39,40,43 that integrated this outcome measure, 5 studies21,26,34,36,39 showed a statistically significant difference in healing rates between groups, 5 studies20,22,29,37,40 showed nonsignificant results, and 1 study43 did not report significant statistical value. From the aforementioned 5 studies that showed significant differences between both groups, 3 studies26,36,39 reported significantly better healing rates for the silver group; the remaining 2 studies21,34 reported healing rates to be better in the comparator group that included octenidine-impregnated dressings and 1% silver sulfadiazine topical cream in addition to phototherapy (3.0J/cm2), respectively.
Tissue changes. The various parameters researchers used to determine wound tissue changes included tissue type score, periwound skin condition, PUSH score reduction, wound severity score, ulcer granulation rate, macerated skin, and amount of granulated tissue. Among the 27 studies, 9 studies18,21,24,30,32,36,41,43,44 mentioned at least 1 tissue type related to outcome measure; of these, 3 studies24,36,44 showed a significant improvement in tissue type with the silver agent and 3 studies18,21,43 showed improvement in the comparator group. The results of 2 of the 9 studies30,32 were nonsignificant, and 1 study41 did not report the statistical (P) value.
Wound recurrence. Wound recurrence rates were reported in 2 studies25,42: 1 study25 reported lower wound recurrence rates when wounds were treated with the silver dressing, and 1 study42 did not report statistical values for wound recurrence rates.
Microbiology. Bacterial presence is used to evaluate wound progression because it provides information about microbial specimens in the wound and their impact on healing. A total of 17 of the selected 27 journal articles18,20,22-25,27,28,30,31,34,35,37-39,41,44 documented microbiological data. The 3 most common microbiological outcome measures examined were increase/decrease of bacterial load, infection, and exudate levels. Significant positive differences after silver treatment were reported in 3 articles,23,27,44 1 study28 favored the comparator treatment, 9 studies18,20,22,24,25,30,34,35,38 reported nonsignificant results, and 4 studies31,37,39,41 provided only descriptive statistics. Microbiological information was provided both qualitatively (where researchers identified different species of bacteria present in the wound) and quantitatively, where researchers identified bacterial load (colony forming units [CFU]/cm2) in the wound.
Information regarding bacterial load was presented in 8 studies20,22,24,25,28,34,39,41; of these, 5 studies20,22,24,25,34 reported their results to be nonsignificant and 2 studies39,41 did not include statistical (P) values. However, 1 study28 showed a significant difference between groups with regard to bacterial load reduction. Furthermore, 10 studies18,23,27,30,31,35,37,38,41,44 reported findings on infection incidence rates or exudate amounts as proxy indicators of infection. Of these studies, 4 reported their results to be nonsignificant18,30,35,38 and 3 studies31,37,41 did not provide statistical values. Among the studies that found a significant difference between treatments, all studies23,27,44 noted that wounds treated with silver products had a lower incidence of infection and better exudate management. The studies examined often-used modifications of pre-established tools that allowed them to quantify outcome measures such as infection rates and prevention.
Pain. Pain was not a common outcome measure evaluated across the clinical trials included in this scoping review; 5 of the 27 studies22,24,28,34,35 provided data regarding pain in ulcer patients, and 1 study24 reported a statistically significant difference between groups (2 studies22,34 did not report the corresponding statistical values and 2 studies28,35 reported nonsignificant results).
Adverse events. Adverse events data were not heavily examined among the clinical trials presented in this review. Although 7 studies20,23,28,30,33,37,39 included data regarding adverse events in patients, none provided information on statistical significance.
Cost of treatment. Treatment cost was not widely reported in the included studies. Three (3) studies presented cost analyses; among those, 2 studies18,19 reported their results as significant and 1 study42 did not provide significance values.
This scoping review of 27 journal articles identified the fact that there are many types of silver dressings used for the treatment of chronic wounds. The study publication dates (1992 to 2015) also indicated that silver dressings have been in clinical use for more than 25 years. The current state of scientific evidence regarding the comparative clinical effectiveness of silver-impregnated versus other dressings for the treatment of chronic wounds is less than robust. Similar to previous reviews,9,11-16 the evidence regarding the effectiveness of silver-based therapies on clinical chronic wound parameters such as wound size, wound exudate, and costs was heterogeneous. The previous reviews included either a limited number of studies ranging from 4 to 14 trials that were published before 20119,11-16 or failed to provide an indepth discussion of the effectiveness of silver treatments on clinical outcomes.46 However, the present scoping review provides an updated analysis of the evidence in the scientific literature regarding silver-based dressings (13 of 27 studies were published after 2011) and examines the effectiveness of silver treatments with regard to several clinical outcome measures.
One of the primary objectives of this review was to identify evidence in the academic and non-peered-reviewed literature on the clinical use of silver dressings on chronic wounds to inform the selection of clinical outcomes for the future evaluation of silver products. Although this search identified parameters such as wound size reduction, healing rate, bacterial load, and pain as being widely evaluated across studies, the lack of standardized methodologies regarding how these outcomes were measured made it difficult to compare findings across studies.
Effectiveness of silver-impregnated dressings. Studies showed heterogeneous evidence on the effectiveness of silver-impregnated dressings on improving clinical outcomes. Although a number of studies found statistically significant positive effects of the silver agent as compared to the control treatment, a similar number of studies found no statistical differences between the 2 treatments. In many of the studies included in this scoping review, it was commonly noted that 1 wound parameter would show statistically significant results while another parameter (whether or not pertaining to the same group of outcome measures) would show no difference between the 2 treatments. Heterogeneous results also were noted among studies that may be attributed to the different study designs and methodologies that were used (eg, mixed interventions, single interventions). The outcome measures used also varied between studies, reiterating the challenge of drawing comparisons. For example, many studies reported on wound area reduction, yet the modes for assessment (eg, camera versus tracing) and reporting (eg, cm versus percent versus threshold) varied substantially between studies. Furthermore, a number of studies did not control wound size by baseline area, which could be considered a major flaw in their study design. Lastly, the silver dressings used in the included studies vary greatly in composition; this, in turn, allowed for distinctive mechanisms of action and might have contributed to the heterogeneous nature of the study findings presented in this review.
Despite the heterogeneous findings, a number of studies reported greater success using a mixed interventions-type approach, where researchers used a silver dressing in conjunction with another treatment. For example, Minatel et al21 (2009) identified that a silver agent used along with phototherapy was more effective in healing wounds than using the silver treatment on its own. The authors also reported much faster healing and granulation rates in the group receiving phototherapy than in the group that did not. However, using mixed interventions study designs where various treatments are being administered might not deliver conclusive results regarding the effectiveness of the silver dressings, per se, due to the problem of confounding factors. Nevertheless, these types of study designs can be useful for providing clinicians information regarding other therapies that can be safely used in conjunction with silver agents and could aid in improving outcomes.
Cost effectiveness of silver treatments. One of the aims of this scoping review was to determine cost effectiveness of using silver dressings compared to other treatments. This review identified 3 journal articles that reported treatment-related costs, 2 of which reported a significant positive difference in the cost-effectiveness of silver alginate and silver mesh dressings as compared to standard topical silver cream treatment. However, this finding is dependent on the brand of dressing used and the clinical context in question. Results are most relevant when a positive effect on clinical outcomes has been established for a particular silver dressing. Information on comparative cost effectiveness of different dressings is critical for health care administrators as they consider the value of different wound treatments.
Research gaps. Given the heterogeneity of evidence regarding the effectiveness of silver treatments in chronic wound care, it is apparent that further research is necessary, particularly in the form of prospective, randomized controlled trials. Studies should be adequately powered and account for potential confounders that might impact the associations between silver dressings and wound healing outcomes. In addition, future studies should evaluate which outcome measures (eg, wound area closure, wound closure rate, infection rates, bacterial load, and recurrence rates) are the optimal indicators of wound healing for use in larger clinical studies. Outcome measures that were scarcely reported include adverse effects, pain, and cost effectiveness; this finding warrants further investigation because they are important factors in wound care. The majority of the studies did not include information regarding safety and adverse effects of treatments; this is critical for future studies so clinicians applying these dressings in wound care practice can be aware of and monitor for potential adverse outcomes. Finally, examining the effectiveness of different silver dressings (based on their composition) could help health practitioners select the best composition/mechanism of action during wound management.
The present scoping review has several limitations to consider. The heterogeneity of interventions (both within and across studies) as well as variable study designs and treatment compositions made it challenging to compare findings across studies. It was noted that multiple journal articles lacked clear definitions of the outcome measures evaluated. For example, 1 study stated that authors were evaluating reduction in wound area, but when reporting their results, they interchangeably used the terms wound area and wound extension, adding to the challenge of determining the favorability of 1 treatment over another. Furthermore, some of the parameters investigated by researchers were qualitative measures; measures were not consistent between studies and therefore were difficult to compare. For example, parameters such as exudate amount were reported at the discretion of the clinician or health care worker involved in the wound care process. Introducing standardized scoring systems or baseline characteristics that clinical researchers could use to assess wounds during healing progression would be useful in eliminating the subjectivity psychometric scales and qualitative observations introduce. Lastly, only English-language articles were included, which could have led to the exclusion of potentially informative articles in other languages.
This scoping review presented an evaluation of the existing literature regarding the use of silver-impregnated dressings in wound care. It may serve to inform, guide, and initiate future systematic review or meta-analysis on chronic wounds and silver treatments. The heterogeneous findings of the scientific literature regarding the impact of silver dressings on clinical outcomes may in part be due to the heterogeneity in terms of the interventions employed (including the type of silver dressing used), study designs, outcomes, and measures. Future clinical trials should focus on evaluating the safety of such dressings and providing information on cost-benefit analyses as well as engaging in the development of clear definitions of the many parameters being evaluated. n
The authors gratefully acknowledge librarian Heather Ganshorn for her assistance with the development of the online search strategy.
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Potential Conflicts of Interest: The present project was funded through a research grant from Exciton Technologies Inc (Edmonton, Canada) as part of a broader collaboration between Exciton Technologies Inc and the University of Calgary, W21C, Calgary, Alberta, Canada. The company was not involved in the design, data collection, analysis, and interpretation of the data, writing of the report, or decision to submit the review for publication.
Ms. Rodriguez-Arguello is a research assistant; Dr. Lienhard is a research associate; Ms. Patel is a medical doctor candidate; and Dr. Geransar is a research manager, W21C Research and Innovation Centre, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Dr. Somayaji is a clinical lecturer; and Dr. Parsons is a clinical professor, Department of Medicine, Cumming School of Medicine. Dr. Conly is the Medical Director, W21C Research and Innovation Centre, Cumming School of Medicine; a professor, Department of Medicine, Cumming School of Medicine; Medical Director, Infection Prevention and Control, Alberta Health Services, Calgary, Alberta, Canada; and Co-Director, Snyder Institute for Chronic Diseases, University of Calgary, and O’Brien Institute for Public Health, Cumming School of Medicine. Dr. Ho is Spinal Cord Injury Research Chair, Professor, and Division Director, Division of Physical Medicine and Rehabilitation, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta. Please address correspondence to: Chester Ho, MD, Spinal Cord Injury Research Chair, Professor and Division Director, AHS Edmonton Zone Clinical Section Head for Rehabilitation, Division of Physical Medicine and Rehabilitation, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada; email: Chester.Ho@albertahealthservices.ca.