Perspective: Silver on Non-Healing Chronic Ulcers

Dear Readers:   Recent reviews find insufficient evidence to recommend the use of silver-containing dressings or topical agents (SIR) to prevent wound infection or to heal infected or contaminated chronic wounds.^1–3 Lack of healing outcomes is counterbalanced by growing evidence supporting favorable outcomes of SIR use on dynamic parameters, such as rate of chronic wound area⁴ or depth⁵ reduction, and patient-oriented outcomes, such as reduction of leakage and odor.⁴ We review a randomized controlled trial (RCT) that reports a 4-week advantage for SIR on biofilm-contaminated wounds and a meta-analysis of RCTs on non-healing chronic wounds citing positive SIR effects on healing rates and patient-oriented outcomes. What can one do when systematic reviews and meta-analyses disagree about efficacy? This Evidence Corner will look deeper into clinical study design issues that may obscure SIR effects. It is time to sort out facts from artifacts and conduct the rigorous RCTs needed to explore the value topical SIR may add in managing chronic ulcers at risk of infection. Laura Bolton, PhD, FAPWCA Adjunct Associate Professor Department of Surgery, UMDNJ WOUNDS Editorial Advisory Board Member and Department Editor

Pressure and Venous Ulcers

Reference: Beele H, Meuleneire F, Nahuys M, Percival SL. A prospective randomised open label study to evaluate the potential of a new silver alginate/carboxymethylcellulose antimicrobial wound dressing to promote wound healing. Int Wound J. 2010;(4):262–270. Rationale: Chronic wounds that form surface biofilms may be at risk of wound infection or of delayed healing. Topical SIR may reduce wound surface colonization and lower that risk. Objective: Compare infection prevention and progression to healing effects of an ionic silver alginate/carboxymethylcellulose (SACMC) dressing with those of a non-silver calcium alginate fiber (AF) dressing in patients with critically colonized (biofilm-infected) chronic pressure and venous leg ulcers. Methods: Thirty-six patients with venous (n = 24) or pressure ulcers (n = 12) clinically judged as at risk of infection based on the presence of wound biofilm and a modified ASEPSIS wound score were randomly assigned to be primarily dressed for 4 weeks with either a silver SACMC or AF. All subjects received appropriate compression or pressure redistribution. Primary outcomes measured during the 4 weeks of treatment were prevention of progression from “critical colonization” to infection measured clinically using the modified ASEPSIS score, prevention of wound deterioration and progression to wound healing, measured as reduction in wound surface area. Results: SACMC subjects experienced a faster rate of surface area reduction than AF subjects during the 4-week study (P = 0.017). Wound deterioration was reported in 1.5% of assessments for the SACMC group and 13% of for the AF group. More wounds progressed from critical colonization to clinical infection in the AF group (P = 0.013). Authors’ Conclusions: SACMC dressing use was associated with fewer infections and faster area reduction than AF dressing use.

Non-healing Chronic Wounds

Reference: Lo SF, Chang CJ, Hu WY, Hayter M, Chang YT. The effectiveness of silver-releasing dressings in the management of non-healing chronic wounds: a meta-analysis. J Clin Nurs. 2009;18(5):716–728. Rationale: Non-healing chronic wounds add to the financial burden of health care. Clinical evidence has been reviewed for effects of silver dressings on infected or contaminated chronic wounds but not for their use on non-healing chronic wounds. Objective: This study explored the clinical evidence supporting use of silver primary dressings on chronic non-healing wounds. Methods: A systematic review and meta-analysis of RCT evidence explored effects of silver dressings on non-healing chronic wounds. PubMed, CINAHL, Cochrane, MEDLINE, British Nursing Index, EBSCO, OCLC, and Proquest reference databases were searched between 1950 and June 2007 for related subjects. These searches were supplemented by hand searches and contact with experts. Results: Eight qualifying RCTs on 1399 participants were selected for analysis. Significant evidence supported SIR effects in improving aspects of wound healing, reduced odor, pain, and exudate (all at P P = 0.028) and improved quality of life (P = 0.013) without associated adverse events. Authors’ Conclusions: This meta-analysis confirms healing effectiveness of silver dressings in chronic non-healing wounds and improving patients’ quality of life. More well-designed RCTs are needed to evaluate these effects.

Clinical Perspective

  The studies reviewed provide a counterpoint to reviews citing lack of evidence,^1–3 which does not necessarily mean “lack of efficacy.” All effects reported are compelling because they studied appropriate subjects and measured relevant outcomes. SACMC dressing should ideally have been compared to an identical CMC control dressing without the silver alginate to prove that the significant effects reported in this small study were caused by silver alone.   It is generally agreed that more rigorous RCTs are needed to conclude that SIR add value to chronic wound management. One such RCT, the VULCAN trial,⁷ which has been critiqued elsewhere,⁸ may have missed important SIR effects by reporting complete healing effects on venous ulcer patients without regard to infection risk and treating patients with SIR for the full study rather than resuming normal dressings once infection risk had passed.   SIR benefits become more apparent on wounds that are at measureable risk of infection or clearly are not healing. This effect may be similar to that of Manuka honey, which is associated with more prominent healing benefits in more serious non-healing ulcers.⁶ Should SIR studies be stratifying analyses or subject assignment by risk severity, wound depth, duration or necrotic tissue, or ASEPSIS score? Better minds than mine with more clinical experience will identify more appropriate variables for infection risk covariate analyses to gain a clearer understanding of SIR as a treatment option potentially affecting subjects at high risk of infection.   SIR are not licensed to heal. They function as microbial barriers helping to manage infection risk. Should systematic reviews analyze early, more dynamic granulation and/or epithelization outcomes to identify capacity of SIR to shepherd wounds past episodes of high infection risk? The study reviewed above by Beele et al used sound operational definitions of infection risk as criteria for enrollment, and clear outcome measures to track wound progress in terms of both infection risk and dynamic healing responses. Once infection risk is lowered, SIR are no longer indicated.   The clinical implication of these findings is that we should pay careful attention to using SIR on the right patients at the right time and measure their efficacy in terms of clinically valid results linked to reducing infection, not merely to healing.

References

1. Storm-Versloot MN, Vos CG, Ubbink DT, Vermeulen H. Topical silver for preventing wound infection. Cochrane Database Syst Rev. 2010;3:CD006478. 2. Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database Syst Rev.2008(1);CD005486. 3. Toy LW, Macera L. Evidence-based review of silver dressing use on chronic wounds. J Am Acad Nurse Pract. 2011;23(4):183–192. 4. Jorgensen B, Price P, Andersen KF, et al. The silver-releasing foam dressing, Contreet Foam, promotes faster healing of critically colonized venous leg ulcers: a randomized, controlled trial. Int Wound J. 2005;2(1):64–73. 5. Jude E, Apelqvist I, Spraul M, Martini J. Prospective randomized controlled study of non-ischaemic diabetic foot ulcers dressed with Hydrofiber® containing ionic silver or calcium alginate dressings. Diabet Med. 2007;24: 280–288. 6. Bolton LL. Leg ulcers and honey: a review of recent controlled trials. In: Cooper R, Molan P, White R, eds. Honey: A Modern Wound Management Product. Shaftesbury, Dorset: Wounds UK Books; 2008:16–29. 7. Michaels JA, Campbell B, King B, Palfreyman SJ, Shackley P, Stevenson M. Randomized controlled trial and cost-effectiveness analysis of silverdonating antimicrobial dressings for venous leg ulcers (VULCAN trial). Br J Surg. 2009; 96:1147–1156. 8. Leaper D. Should one size fit all? An overview and critique of the VULCAN study on silver dressings. Int Wound J. 2011;8(1):1–4.