Role of Cadexomer Iodine in wound bed preparation for healing of Chronic Wounds: Meta-Analysis
Successful management of chronic wounds remains a challenge to physicians, owing to the existence of new, resistant strains of microbiota, and subsequent development of diverse biofilms1 associated with such wounds. The availability of a variety of over-the-counter topical ointments further adds to the challenge faced in the medical fraternity.
Proper choice of a topical dressing, coupled with timely intervention can go a long way in managing chronic, non-healing wounds, as has been highlighted 2, 3 over and again in previous studies. Among the widely used iodine-based dressings available, Cadexomer Iodine has strengthened its position in the last decade. Mounting evidence now suggests that Cadexomer Iodine is highly efficacious, not only in managing venous leg ulcers and pressure ulcers but also in healing chronic wounds4, 5, 6.
Cadexomer Iodine consists of biodegradable spherical hydrophilic beads (size range 100-315 μm) of cadexomer starch, which incorporate 0.9% w/w iodine. It is available in multiple forms like powder, gel/ointment, and dressing formats, this molecule has a dual mechanism of action. Starch helps in the absorption of exudates, pus, and wound fluids whereas iodine acts as the main antimicrobial against biofilms7.Such mechanisms aid in controlling the barriers to wound healing, providing a favorable wound bed for faster healing 8.
Acknowledging the accumulating evidence in support of the usefulness of CI in managing such chronic, non-healing wounds, Diabetes India now recommends CI for selected empirical antibiotic regimens for mild and non-limb threatening infections.9
A recent in-depth analysis was undertaken by Kevin Woo et al. focusing on the impact of Cadexomer Iodine in reducing the barriers to healing such as exudate, slough, and bioburden, leading to a favorable wound bed preparation10. To summarise the clinical evidence supporting CI, the team conducted a systematic review and meta-analysis of scientific articles over the last 40 years.
This review has been published in the International Wound Journal.
For the study design, a systematic literature search was performed using the related to cadexomer iodine and its brand names, iodine beads or iodine start AND ("wound healing" OR "chronic wound"), and no lower date limit was conducted on Embase and PubMed to identify relevant studies on 24 November 2020.
480 studies (including prospective and retrospective design) that evaluated the use of Cadexomer Iodine along with relevant wound healing outcomes in patients of any age or with any risk factors for complications were included.
Outcome measures assessed were exudate management, reduction in pus (more recently termed purulence), slough and cellular debris, and bioburden (including biofilm).
Meta-analyses were performed using a fixed-effectswounds (12 < 50%) or random-effects model (12 ≥ 50%) depending on statistical heterogeneity. Dichotomous outcomes were reported as relative risk (RR) and continuous outcomes as mean difference (MD), with 95% confidence intervals.
Data analysis highlighted some interesting results, as summarised below.
Reduction in excessive wound exudates -
Among eight RCTs reporting on exudate levels, notable results by Harcup et al.11 exhibited a significant reduction in exudate levels by week 4 of treatment with CI (P < .001). Laudanska12 reported a significantly faster reduction in exudate levels with Cadexomer Iodine treatment following 1 and 2 weeks (P < .01), and 4 and 6 weeks of treatment compared to SOC (P < .001), whereas Skog and coworkers13 reported that treatment with Cadexomer Iodine for 6 weeks was significantly more effective for reducing exudate compared to SOC (P < .005). Hansson and team 14 reported that following a 12-week intervention with CIOD, 70% of the ulcers had no exudate, compared to 52% and 44% in the hydrocolloid and paraffin gauze groups, respectively.
Reduction in cellular debris:
Wound slough and purulence- Study by Hansson et al.14 confirmed a significant reduction in the percentage of slough in chronic wounds using Cadexomer Iodine compared with SOC (P < .05).
Skog et al. observed a marked debriding effect on VLU wounds due to reduction of pus (purulence) and removal of cellular debris from the wound bed. In yet another study by Laudanska and colleagues,12 the reduction in pus and debris was noted to be more rapid following Cadexomer Iodine intervention in VLUs compared to SOC.
On performing meta-analysis10 based on data from such studies, pus and debris after 6–8 weeks were noted to be significantly reduced in CIOD experimental group as compared to the SOC control group. (MD = 9.52, 95% CI: 5.27–13.77, P < .0001).
Reduction in wound bioburden-
Hillstrom15 reported a significant reduction in Staphylococcus aureus (P < .001) using semi-quantitative methods with an improvement in infection in 16 of 23 patients in the Cadexomer Iodine group compared with 0 of 18 groups in the SOC group. These results were supported by similar results from other studies13. Lindsay et al.16 highlighted that CIOD treatment resulted in the elimination of organisms in most cases, and this was associated with reduced odor and improvement of the ulcer. Significant reductions in streptococci, enterococci, and Enterobacteriaceae such as Proteus and Klebsiella species were noted (P < .001 and P < .01, respectively) in other trials, following 6 weeks of intervention with CIOD compared with SOC 13,17.
The reviewers arrived at some key facts from the above results.
1. Cadexomer Iodine helps in reducing the pus, debris, slough, exudates from the wound site, which act as barriers to effective wound healing.
2. The constant release of iodine warrants a wide spectrum antimicrobial effect against microorganisms like Staphylococcus aureus, streptococci, enterococci, and Enterobacteriaceae, thus reducing the wound bioburden.
3. Existing evidence highlights the fact that CI helps in favorable wound bed preparation which is very vital for enhancing chances of tissue repair in chronic wounds.
Observing these results, the research team concluded that, "An essential part of any treatment protocol for a chronic wound is to minimize or remove the barriers to healing by performing appropriate wound bed preparation as described by wound experts using the T.I.M.E acronym (non-viable Tissue, Infection, Moisture imbalance, Edge, not advancing or undermining).10 The data demonstrate consistent positive outcomes that CIOD treatment has on chronic stalled wounds through the removal of barriers that impede wound healing. The data presented in this systematic review and meta-analysis confirm that treatment with CIOD should be considered as part of wound bed preparation and treatment protocols in persons with chronic non-healing wounds."
The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Cadexomer Iodine, click HERE
1. Sun H, Pulakat L, Anderson DW. Challenges and New Therapeutic Approaches in the Management of Chronic Wounds. Curr Drug Targets. 2020;21(12):1264-1275. doi: 10.2174/1389450121666200623131200. PMID: 32576127.
2. Frykberg, R. G., & Banks, J. (2015). Challenges in the Treatment of Chronic Wounds. Advances in wound care, 4(9), 560–582. https://doi.org/10.1089/wound.2015.0635
3. Kavitha, K. V., Tiwari, S., Purandare, V. B., Khedkar, S., Bhosale, S. S., & Unnikrishnan, A. G. (2014). Choice of wound care in diabetic foot ulcer: A practical approach. World journal of diabetes, 5(4), 546–556. https://doi.org/10.4239/wjd.v5.i4.546
4. Roche, E. D., Woodmansey, E. J., Yang, Q., Gibson, D. J., Zhang, H., & Schultz, G. S. (2019). Cadexomer iodine effectively reduces bacterial biofilm in porcine wounds ex vivo and in vivo. International wound journal, 16(3), 674–683. https://doi.org/10.1111/iwj.13080
5. Holloway, G. A., Jr, Johansen, K. H., Barnes, R. W., & Pierce, G. E. (1989). Multicenter trial of cadexomer iodine to treat venous stasis ulcer. The Western journal of medicine, 151(1), 35–38.
6. Raju R, Kethavath SN, Sangavarapu SM, Kanjarla P. Efficacy of Cadexomer Iodine in the Treatment of Chronic Ulcers: A Randomized, Multicenter, Controlled Trial. Wounds. 2019 Mar;31(3):85-90. Epub 2019 Jan 31. PMID: 30720444.
7. Fitzgerald, D. J., Renick, P. J., Forrest, E. C., Tetens, S. P., Earnest, D. N., McMillan, J., Kiedaisch BM, Shi L ,Roche E. D. (2016). Cadexomer iodine provides superior efficacy against bacterial wound biofilms in vitro and in vivo. Wound Repair and Regeneration, 25(1), 13–24. doi:10.1111/wrr.12497
8. Schultz GS, Sibbald RG, Falanga V, et al. Wound bed preparation: a systematic approach to wound management. Wound Repair Regen. 2003;11(Suppl 1):S1-S28.
9. Rayman et al. Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes (IWGDF 2019 update). Diab Metab Res Rev. 2020. e3283.
10. Woo K, Dowsett C,Costa B, Ebohon S, Woodmansey EJ, Malone M. Efficacy of topical cadexomer iodine treatment in chronic wounds: Systematic review and meta- analysis of comparative clinical trials. Int Wound J.2021;1–12. https://doi.org/10.1111/iwj.13560
11. Harcup JW, Saul PA. A study of the effect of cadexomer iodine in the treatment of venous leg ulcers. Br J Clin Pract. 1986;40:360-364.
12. Laudanska H, Gustavson B. In-patient treatment of chronic varicose venous ulcers. A randomized trial of cadexomer iodine versus standard dressings. J Int Med Res. 1988;16:428-435.
13. Skog E, Arnesjö B, Troëng T, et al. A randomized trial comparing cadexomer iodine and standard treatment in the out-patient management of chronic venous ulcers. Br J Dermatol. 1983;109:77-83.
14. Hansson C. The effects of cadexomer iodine paste in the treatment of venous leg ulcers compared with hydrocolloid dressing and paraffin gauze dressing. Int J Dermatol. 1998;37:390-396.
15. Hillstrom L. Iodosorb compared to standard treatment in chronic venous leg ulcers—a multicenter study. Acta Chir Scan Suppl. 1988;544:53-56.
16. Lindsay G, Latta D, Lyons KGB. A study in general practice of the efficacy of cadexomer iodine in venous leg ulcers treated on alternate days. Acta Ther. 1986;12:141-148.
17. Troëng T, Skog E, Arnesjö B, Gjöres JE, Bergljung L, Gundersen JEA. A randomised multicentre trial to compare the efficacy of cadexomer iodine and standard treatment in the management of chronic venous ulcers in out patients. In Fox J, Fisher H, eds. Cadexomer Iodine. Stuttgart: Schattauer Verlag; 1983:43-50.
Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Before Joining Medical Dialogues, he has served at important positions in the medical industry in India including as the Hony. Secretary of the Delhi Medical Association as well as the chairman of Anti-Quackery Committee in Delhi and worked with other Medical Councils in India. Email: email@example.com. Contact no. 011-43720751