Cadexomer Iodine vs Silver Dressings in Exuding Wounds: Review

Wound healing is a sequential process that consists of four overlapping phases of coagulation, inflammation, migration– proliferation (including matrix deposition), and remodeling. Acute wounds heal in a sequenced and timely manner as mentioned above whereas chronic wounds remain stalled in one of these stages (classically, the inflammatory phase) for a multitude of reasons. The presence of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) present in the exudate of wounds differentiates acute and chronic wounds (2,3).

Exudate is a generic term used to identify liquid produced from wounds. It is generated as part of the inflammatory response and is vital for the healing process. It can be regarded as a transport mechanism which delivers various components to the wound bed. Various types of wounds produce varying amounts of exudates (4). Exudative Wounds like burns produce more than 5000g/m2 /day of exudate and venous leg ulcers produced between 4000 and 12,000g/m2 /day of exudate.

The inflammatory process is important. In full-thickness burn injuries and chronic wounds such as pressure ulcers, venous ulcers, and diabetic foot ulcers, this normal healing process is hampered leading to the chronicity of the wound (5). Wound bed preparation is of utmost importance to improve healing. Moisture balance is of paramount importance for exudate management in wound healing. International Advisory Board on wound bed preparation has prepared the TIME principle of wound bed preparation which are Tissue (viability), Inflammation and/or infection, Moisture imbalance, and advancement of the edge of the wound (6). Despite the relevance of these TIME paradigm in wound healing, inflammation and infection control, healing of chronic wounds may be delayed due to bacterial colonization (7).

After considering the underlying causes of tissue damage, tissue perfusion, and bacterial load a wound dressing is found to be most functional. Presently there is a myriad of options available like the moisture-retentive films, hydrocolloids, foams, alginates, and antimicrobial dressings like the impregnated silver and iodine (8) for wound healing. The use of a topical antimicrobial agent is clinically indicated when a wound is regarded as critically colonized (9).

When a reduction in microbial load is required, the decision to select an antimicrobial depends on the ability of the dressing to manage increased exudation, remove necrotic tissue, reduce malodor, conform to the site and shape of the wound, perform wound bed preparation functions, satisfy patients' expectations and meet treatment goals (10). The choice of antimicrobials depends on the specificity and efficacy of the agent, its cytotoxicity to human cells, it's potential to select resistant strains, and its allergenicity. There are a wide range of topical antimicrobial agents currently used like chlorhexidine, products containing iodine (cadexomer iodine and povidone-iodine), and products containing silver (silver sulfadiazine and silver-impregnated dressings) (10).

History: Even though silver has a long history of its use, its first documented use as a topical silver nitrate application for chronic wounds or ulcers by John Woodall (7).

Mechanism of action: They work by competing with other cations for adsorption sites on the cell. At the molecular level, they cause inhibition of bacterial enzymes and interferes with respiration at the cell membrane level and also Ionic silver forms complexes with nucleic acid bases thus contributing to the lethal efficacy (10).

The spectrum of activity: They have broad bactericidal spectrum activity with efficacy against several common wound pathogens like Pseudomonas aeruginosa, and others including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and extended-spectrum-lactamase producers (7).

Release: Silver ions are typically released from dressings through oxidation occurring upon contact between the silver ions and fluid in the wound environment. Nanocrystalline silver products were developed to release smaller silver particles faster to increase antimicrobial activity (7).

Safety: Transient staining of the surrounding skin can occur with silver dressings depending on the duration of use and permanent discolouration was possible though. Argyria is unlikely but sensitivity to silver can occur. Cytotoxicity has been recognized with the use of silver cream and ointments. silver sulfadiazine is associated with the release of the sulfonamide rather than silver, and it has been associated with severe blood and skin disorders (10).

Release: It is a chemically modified starch which consists of a helical polysaccharide backbone to which carboxymethyl groups have been added. It exists as 0.1-0.3mm hollow microspheres with Iodine physically trapped in the centre at 0.9% concentration. It is particularly effective in the treatment of venous ulcers, diabetic foot ulcers, decubitus ulcers, and infected wounds (11/zhou).

Mechanism of action and release: it modulates wound pH, via an ion-exchange mechanism which has two vital outcomes. They are the enhancement of the antimicrobial activity of iodine and a unique anti-inflammatory property (12/brett). It also has wound cleansing and desloughing properties. The abundance of hydrogen and hydroxide moieties in the cadexomer molecule allows for a great deal of hydrogen bonding with the wound exudate to create a gel. This allows debris within a wound to be removed with the exudate as it is drawn into the matrix.

The spectrum of activity: it exerts its action on several pathogens like Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA) (13/angel).

Safety: Transient pain within the first hour of application which may be described as 'stinging' or 'smarting' sensation. Some patients can develop a contact allergy. Care must be taken while using it for patients with thyroid disorders (13).

Various clinical trials as published in the "Management of wound infection" show that Silver is used for burns and skin grafting as a prophylactic to prevent infection. Most animal studies found no adverse effects on healing. Research with cadexomer iodine shows reduced bacterial counts and improved healing. Data published in this series also shows that iodine shows a better antimicrobial spectrum than silver against fungi, endospores & viruses. There were also reports of the development of silver-resistant bacteria from the wound of a burn patient who was treated with a silver dressing (10).

In another study by Philips et al found that cadexomer Iodine is found to show a better antimicrobial efficacy against mature P.aeruginosa biofilm as compared to other antimicrobials like the silver, polyhexamethylene biguanide, honey, and ionic morphous silver (14).

Various systemic reviews considering silver antimicrobial agents have been hampered by the lack of RCTs of acceptable quality. Studies have also shown that Silver dressings were not recommended perhaps due to a finding that significant reductions in ulcer size observed at two and four-week intervals for a silver impregnated activated charcoal dressing were not sustained at a six-week follow-up (7).

One of the trials using silver found that when comparing silver-containing dressing with a non-silver containing dressing, it has found better short term healing effects with silver dressings but the long term healing effects were unclear. In contrast, Various reviews in the past have shown that cadexomer iodine promotes wound healing more than other (non-silver) dressings as shown by both animal and human research (7).Multiple studies have shown that considerable reduction in pus, debris, the pain of the ulcers, and accelerated wound healing when using the cadexomer-iodine was seen (13).

Cadexomer iodine is found to be more cost-effective than other dressings like hydrocolloid dressings and paraffin gauze, standard treatment (gentamicin solution, streptodornase/strepto- kinase, dry saline gauze) (15). At the same time, Silver products are generally perceived to be expensive in comparison to other treatments. A retrospective analysis of wound care episodes found clients treated with silver antimicrobials received more visits, had a longer treatment duration, with shorter intervals between visits than clients treated with 'other' dressings (16).

Judicious use of topical antimicrobials should be done. Awareness of the efficacy and toxicity of the antimicrobials is necessary before using them. Cadexomer iodine is bactericidal to all gram-positive and gram-negative bacteria and promotes a moist wound environment through a 3D starch lattice formed into spherical microbeads with iodine trapped in between. This preparation effectively improves healing in chronic exudative wounds and can be used as an effective antimicrobial agent in wound management.

1. Han G, Ceilley R. Chronic Wound Healing: A Review of Current Management and Treatments. Adv Ther. 2017;34(3):599-610. doi:10.1007/s12325-017-0478-y

2. Dabiri G, Damstetter E, Phillips T. Choosing a Wound Dressing Based on Common Wound Characteristics. Adv Wound Care (New Rochelle). 2016;5(1):32-41. doi:10.1089/wound.2014.0586

3. Cutting, K. 2003. Wound exudate: Composition and functions. British journal of community nursing, 8, p.suppl 4-9.

4. Bates-Jensen BM. The Pressure Sore Status Tool a few thousand assessments later. Adv Wound Care. 1997;10(5):65-73.

5. Weller, C. (2009). Interactive dressings and their role in moist wound management. In Advanced Textiles for Wound Care: A Volume in Woodhead Publishing Series in Textiles (pp. 97-113). Academic Press. https://doi.org/10.1533/9781845696306.1.97

6. Schultz GS, Barillo DJ, Mozingo DW, Chin GA; Wound Bed Advisory Board Members. Wound bed preparation and a brief history of TIME. Int Wound J. 2004;1(1):19-32.

7. Miller, C., & Smith, H. (2011). Examining the efficacy of silver and cadexomer iodine dressings in treating wounds compromised by bacterial burden: A review of the literature.

8. Broussard KC, Powers JG. Wound dressings: selecting the most appropriate type. Am J Clin Dermatol. 2013;14(6):449-459.

9. Best Practice Statement: The use of topical antiseptic/antimicrobial agents in wound management. Aberdeen: Wounds UK; 2010.

10. European Wound Management Association (EWMA). Position Document: Management of wound infection. London: MEP Ltd, 2006.

11. Zhou LH, Nahm WK, Badiavas E, Yufit T, Falanga V. Slow release iodine preparation and wound healing: in vitro effects consistent with lack of in vivo toxicity in human chronic wounds. Br J Dermatol. 2002;146(3):365-374.

12. Brett DW. Cadexomer iodine: A fresh look at an old gem. WP&R Journal 2019; 27(1):42-48.

13. Angel DE, Morey P, Storer JG, Mwipatayi B. The great debate over iodine in wound care continues: a review of the literature. Wound Practice and Research. 2008;16(1):6-21.

14. Phillips PL, Yang Q, Davis S, et al. Antimicrobial dressing efficacy against mature Pseudomonas aeruginosa biofilm on porcine skin explants. Int Wound J. 2015;12(4):469-483.

15. Apelqvist J, Ragnarson Tennvall G: Cavity foot ulcers in diabetic patients: a comparative study of cadexomer iodine ointment and standard treatment. An economic analysis alongside a clinical trial. Acta Dermato-Venereologica 1996, 76(3):231-235.

16. Wang J, Smith J, Babidge W, Maddern G: Silver dressings versus other dressings for chronic wounds in a community care setting. Journal of Wound Care 2007, 16(8):352- 356.