Growing role of Cadexomer Iodine in wound care: Review
Iodine, a natural element of the halogen group, is an essential nutrient in the body. It possesses antiseptic properties and hence has been used throughout history in wound care. Iodine is a dark metallic crystalline solid (1) and is a component of the hormone thyroxine which aids in physical and mental development (2). As iodides, it is found in the seaweed and kelp. Its discovery was serendipitous by Barnard Courtois while manufacturing gun powder. Gay-Lussac named the new element 'iode' (Greek-ioeides) meaning violet (3).
There are various formulations of Iodine available presently. The most common ones include Povidone Iodine, Inadine, and Cadexomer iodine. Povidone-iodine is a combination of molecular iodine and polyvinylpyrrolidone surfactant/iodine complex having free Iodine at approximately 1 ppm. Inadine consists of a knitted viscose fabric impregnated with a polyethylene glycol base containing 10% povidone-iodine equivalent to 1% available iodine. Cadexomer-iodine contains 0.9% iodine within a three-dimensional starch lattice, formed into spherical microbeads.
Various studies in the past have shown that the use of povidone-iodine delayed wound healing and did not reduce bacterial growth. It was also observed that the povidone-iodine application did not show a long-lasting bactericidal effect. Toxicity to vascular endothelium was another feature that limited the use of povidone-iodine (1). Research shows that when compared to povidone-iodine, the other formulation of iodine i.e. Cadexomer iodine showed promising results by accelerating the rate of epidermal cell migration, reducing the pathogens, and reducing the symptoms (1).
Cadexomer Iodine:
Cadexomer Iodine 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 exudative wounds like diabetic foot ulcers, decubitus ulcers, infected wounds, and venous ulcers, (4).
Cadexomer iodine has various features which include the following:
Fluid absorption:
Because of its structure and having an abundance of hydrogen and hydroxide moieties, it helps to absorb wound fluid up to six times its weight by creating a gel (5).
Iodine release:
Cadexomer Iodine continuously releases free iodine as it is being used constantly in the wound. It also modulates wound pH, via an ion-exchange mechanism thus enhancing the antimicrobial and anti-inflammatory activity. It shows initial bacteriostatic activity by sustained and slow initial release and by dissolving the matrix. (5). A state of equilibrium is established which allows for a constant level of iodine available in the wound to kill pathogens. As iodine is slowly consumed, equilibrium is shifted and exerts its bactericidal action until all iodine is consumed from the wound (5).
Desloughing:
By having abundant hydrogen and hydroxide moieties and allowing a great deal of hydrogen bonding, Cadexomer iodine creates a gel that allows debris within a wound to be removed with the exudate as it is drawn into the matrix causing autolytic debridement. Various studies have also supported the desloughing property of Cadexomer iodine and a significant improvement was observed when Cadexomer iodine was used in the ulcer size, exudate, erythema, odor, pus, and debris (5, 6).
Anti-Inflammation:
Various studies evaluated the anti-inflammatory properties of Cadexomer iodine. Elevated levels of proteases are seen in chronic wounds which delay the healing process. Cadexomer matrix appears capable of adjusting the pH of chronic wound fluids from a pH range of maximum protease activity to a pH range of minimum protease activity. In vivo reduction of matrix metalloproteinases in the chronic wound and protection of newly formed extracellular matrix potentially allowing the re-epithelialization of the wound is seen (7).
Cadexomer iodine also has a pro-oxidant effect via the release of iodine into the wound. The iodine enters the microbial cells and reduces the glutathione and NAD(P)H. This causes hydrogen peroxide levels to increase, ultimately increasing fibroblast proliferation. Iodine from the Cadexomer iodine interacts with specific cell types in the wound. In a study, Cadexomer iodine induced a threefold increase of TNF-α production by the macrophages (8). Cadexomer can also produce significant reepithelization of the tissues.
Cadexomer Iodine is an effective debridement and antiseptic agent for chronic exudative wounds.
Clinical studies/trials involving Cadexomer Iodine:
Most studies involving Cadexomer-iodine are on human subjects. In chronic wounds such as diabetic foot ulcers, venous leg ulcers or pressure ulcers have demonstrated a positive effect on wound healing. Some of the important ones include
• Moberg et al compared cadexomer-iodine (n=16) to patients receiving standard treatment (n=18) which comprised of saline, enzyme-based or non-adhesive dressings. Considerable reduction in pus, debris, and pain of the ulcers in the cadexomer-iodine group, as well as accelerated wound healing, was seen (1,9).
• Another study by Danielson found that cadexomer-iodine in venous leg ulcers colonized with Pseudomonas aeruginosa showed median ulcer area reduction and negative cultures after 1 and 12 weeks of treatment (1).
• Another effective study of cadexomer iodine by Skog et al on 93 patients with recalcitrant venous leg ulcers found a 34% decrease in ulcer size compared with 5% in the other treatment groups (1,10).
• A study by Ormiston of cadexomer iodine in chronic venous ulcers found that ulcers treated with cadexomer iodine healed nearly twice as quickly during the first 12 weeks and the epithelium also grew faster (11).
• A randomized control trial by Hansson comparing cadexomer iodine paste with hydrocolloid dressing and paraffin gauze dressings for venous leg ulcers showed a faster wound closure and was found to be an efficient, cost-effective alternative to hydrocolloid and paraffin gauze dressings (12).
• Another multicentre trial by Tröeng using cadexomer iodine on chronic venous ulcers found that the use of cadexomer iodine was associated with more rapid wound closure and the 'cleansing' of ulcers and that the removal of organisms relates to more rapid re-epithelialization (13).
• A trial of cadexomer iodine by Steele in the management of Venous Leg Ulcers found that cadexomer iodine reduced pain, odor, and caused accelerated wound closure (14).
• Another study by Holloway et al found that the mean ulcer closure rate was more than twice as great using cadexomer iodine as with standard therapy of wet-to-dry dressing with saline-soaked gauze pads and elastic compression bandage. They also found that ulcers treated with cadexomer iodine showed less pain, exudate, pus, and debris, and more rapid development of granulation tissue (15).
• A retrospective analysis by Sundberg found that since 1982 a published body of evidence containing almost 10,000 patients supports the efficacy and safety of cadexomer iodine in treating a variety of ulcer types and burns, including sloughy, and infected ("dirty") wounds (16).
L.H.Zhou et al conducted a study that examined the effects of varying concentrations of cadexomer iodine on human fibroblasts in culture and neonatal skin explants and also examined biopsies of chronic exudative wounds being treated with cadexomer iodine (4). They found that cadexomer iodine at concentrations up to 0.45% did not affect the cell viability, morphology, proliferation of human cultured fibroblasts. They also found a lack of tissue toxicity with cadexomer iodine in vitro on human fibroblasts. They also advised discontinuing treatment with cadexomer iodine once the exudate has diminished and proper wound bed preparation is achieved.
Studies showed cadexomer iodine to be as effective as or more effective than standard treatments
Comparison of Cadexomer iodine and Povidone-iodine:
Povidone-iodine is a knitted viscose fabric with 1% available iodine while cadexomer iodine has 0.9% available Iodine. Cadexomer has antimicrobial properties like povidone and an additional desloughing nature. Unlike Povidone cadexomer is biodegradable by amylases from wound fluid. While povidone is mostly prescribed for ulcerative wounds, minor burns, and traumatic skin loss cadexomer is prescribed in chronic exudative wounds where slough, infection, or the risk of infection is an issue (1).
Conclusion:
Thus, it can be concluded from the ample body of high-quality clinical evidence in support of cadexomer iodine that Cadexomer-iodine has a positive impact on healing in the chronic wound environment. It is non-toxic to human fibroblasts and has an additional antiseptic property of trapping microorganisms. By judicious use of this form of iodine, wounds can be better-taken care of.
The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Cadexomer Iodine, click here
References:
1. 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.
2. Cavalieri R. Iodine metabolism and thyroid physiology: current concepts. Thyroid 1997;7(2):177–181.
3. Abrahams GE. The history of iodine in medicine part 1: From discovery to essentiality [Internet]. The Original Internist: 2006. Available from: http://www.optimox.com/iodine-study-14.
4. 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.
5. Brett, D. (2019). Cadexomer iodine: A fresh look at an old gemWound Practice and Research, 42-48.
6. Jacobsson S, Rothman U, Arturson G, Ganrot K, Haeger K, Juhlin I. A new principle for the cleansing of infected wounds. Scand J Plast Reconstr Surg 1976;10:65–67.
7. Greener B. Absorption of chronic wound fluid by a unique cadexomer polysaccharide lowers the pH of the fluid and may indirectly inhibit the activity of proteolytic enzymes. Poster presentation from The Wound Healing Society 16th Annual Meeting & Exhibition; May 14–17, Scottsdale (AZ): 2006.
8. Moore K, Ruge F, Harding KG. T-lymphocytes and the lack of activated macrophages in wound margin biopsies from chronic leg ulcers. Br J Dermatol 1997;137:188–194.
9. Moberg S, Hoffman L, Grennert M-L et al. A randomized trial of cadexomer-iodine in decubitus ulcers. J Am Ger Soc 1983; 31(8):462-465.
10. 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.
11. Ormiston MC, Seymour MT, Venn GE, Cohen RI, Fox J. A controlled trial of Iodosorb in chronic venous ulcers. BMJ 1985;291:308–310.
12. 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.
13. . Troeng T, Skog E, Arnesjo B, Gjores JE, Bergljung L, Gundersen J. A randomized multi-centre trial to compare the efficacy of cadexomer iodine and standard treatment in the management of chronic venous ulcers in outpatients. In: Fox JA, Fischer H (Eds). Cadexomer Iodine. Stuttg|rt: Schattauer Verlag; 1983:43–50.
14. Steele K, Irwin G, Dowds N. Cadexomer iodine in the management of venous leg ulcers in general practice. The Practitioner 1986;230:63–68.
15. Holloway GA, Johansen KH, Barnes RW, Pierce GE. Multicenter trial of cadexomer iodine to treat venous stasis ulcer. West J Med 1989;151:35–38.
16. Sundberg J, Meller R. A retrospective review of the use of cadexomer iodine in the treatment of chronic wounds. Wounds 1997;9(3):68–86.
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