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, 3, 4A, 4B, 4C, and 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.