Role of Cadexomer iodine in Decubitus ulcers: Review
Iodine based preparations have been in use for a long time for preventing post-surgical and other wound infections. Iodine, a trace element from the halogen group was discovered serendipitously by Bernard Courtois (1). Since its discovery, iodine-based preparations have been extensively used for various ailments. Later in the mid-20 th century, Iodophors were prepared which allowed a controlled release of Iodine. Of these the two widely used iodophors are the Povidone-iodine and Cadexomer Iodine (2).
Cadexomer Iodine:
Various studies in the past have shown the efficacy of cadexomer iodine as an antimicrobial agent and its effect on wound debridement, stimulation of granulation tissue, and overall wound healing (3). Cadexomer iodine, a dry powder, has 0.9% iodine within a three- dimensional starch lattice, formed into spherical microbeads that range in diameter from 100 to 315µm. Each microbead is a highly hydrophilic, three-dimensional network of a modified starch polymer containing iodine, which is physically immobilized within the matrix at a concentration of 0.9%. One gram of powder can absorb as much as 7 ml of fluid. As the pore size increases with fluid uptake the iodine is released slowly, and a concentration gradient of iodine is established with the lowest concentration at the wound surface.
Cadexomer Iodine has highly absorbent antimicrobial action and facilitates desloughing (4). Cadexomer Iodine is excreted in the urine and degraded by the amylases present in the wound fluid. It is indicated in chronic exudative wounds like the chronic leg ulcers, pressure ulcers or decubitus ulcers, diabetic ulcers, and any ulcers where an infection is present or suspected (4).
What are Decubitus ulcers?
Decubitus ulcers are skin and soft tissue injuries that form because of constant or prolonged pressure exerted on the skin. These are commonly termed as bedsores or pressure ulcers. These occur at various bony areas such as the ischium, greater trochanter, sacrum, heel, malleolus, and occiput. Their cause is multifactorial. Loss of sensory perception, impaired loss of consciousness, decreased mobility include the main causes of these decubitus ulcers (5). Besides these, certain external factors like pressure, friction, shear force, and moisture, and other internal factors like fever, malnutrition, anemia, and endothelial dysfunction may also speed up the process of these lesions (6).
Cadexomer iodine in Decubitus Ulcers
A lot of research supported the use of Cadexomer iodine in the treatment of ulcers.
Cristopher Frank et al in a study mentioned that Cadexomer Iodine is safe and effective in decreasing bacterial burden in the superficial compartment (7).
Ohtani et al studied the effects of cadexomer on the production of inflammatory cytokines or angiogenic factors by macrophages derived from human monocytes. They found that cadexomer iodine significantly increased the production of IL-1β, TNF-α, and VEGF which helped in wound healing in various ulcers (8).
As several studies have shown rapid healing of Decubitus ulcers with cadexomer iodine, Sven Moberg et al conducted a randomized controlled trial to compare the effectiveness of cadexomer iodine with that of the standard regimen of treatment in three speciality units of different hospitals (9).
Methodology:
Forty-five male and female hospitalized patients who had decubitus ulcers were included in the trial. Moribund patients, suspected malignant patients, suspected iodine sensitive patients, and those having psychiatric illnesses were excluded from the study. Out of 45, 7 were lost due to various reasons like death, rapid deterioration of the condition, incorrect selection, severe exacerbation of psoriasis. Of the remaining 38 patients, 19 were allocated in the standard treatment and 19 in the cadexomer iodine group. After randomization, few patients were lost in both groups due to various reasons.
Ulcers were evaluated and classified as deep or superficial by a clinical assessment, and ulcer area was measured by planimetry performed on a tracing of the outline of the ulcer and by measurement of the longest diameter. The amount of pain the patient experienced from the ulcer and the quantity of pus and debris were assessed using a visual analogue scale.
Patients were allocated blindly and at random for treatment with cadexomer iodine or the standard treatment used in each hospital. Standard treatment was individualized for each patient based on the appearance of the ulcer and surrounding skin. It included saline dressings, enzyme-based debriding agents, and non-adhesive dressings. Cadexomer iodine was applied daily to ulcers in a layer approximately 3 mm thick and was removed after 24 hours under a stream of water or saline or with a wet swab.
The principle of treatment was the attention to nutrition; improvement of hygiene; and removal of localized pressure by use of decubitus mattresses, turning the patient every two to three hours, and optimal mobilization. The switching of the patient to the other treatment group was done if the ulcers were not abating or were getting worse after three weeks. The investigator could switch the patient for five weeks. If a positive response was observed during the first three weeks, treatment was continued until the ulcer healed or for five more weeks, whichever occurred first. Change of ulcer area and changes in analog scales for pain and pus and debris were evaluated using a correlated t-test; nominal response categories were evaluated using Fisher's exact probability test.
Results:
At the end of the trial, the researchers saw the following results
• There were 2 dropouts from the trial. Fourteen patients continued treatment with cadexomer iodine and 13 continued with the standard treatment.
• The reduction of ulcer area was 19.5% of the original area in the standard treatment group and 31% of the original area in the cadexomer iodine treatment.
• 8 ulcers treated with cadexomer iodine had more than 50% reduction of the area compared to the standard treatment group.
• 3 patients from the standard treatment group were shifted to the cadexomer iodine group and a 50% mean reduction in ulcer area was observed after five weeks.
• Two patients unresponsive to cadexomer iodine were switched to the standard treatment and showed a mean reduction in ulcer area of 29% after five weeks.
• After 8 weeks of treatment, there were 76% and 57% of the original ulcer areas in the cadexomer iodine and standard treatment groups, respectively.
• Six ulcers had healed after eight weeks of treatment with cadexomer iodine compared with one in the standard treatment group.
• Pain from ulcers was reduced to half in both the groups after 3 weeks but significantly reduced in the cadexomer group after 8 weeks.
• There were no major side effects except for a mild smarting sensation and a psoriatic lesion in one patient.
Thus, the researchers observed that there was a significant reduction of ulcer areas in both groups. But within three weeks, they found that cadexomer iodine had a significantly greater effect on re-epithelialization and, after eight weeks, a significantly greater effect on total healing.
The researchers also analyzed that among the two criteria they set like the absolute reduction and the percentage reduction of the area and noted that the cadexomer iodine group responded better. They also observed that the amount of re-epithelialization per centimeter was better in the cadexomer iodine group. The cadexomer iodine group showed a mean re- epithelialization rate of 0.54 cm2/ cm of circumference during the eight-week trial, compared with 0.44 cm2 in the standard group.
The authors also noted from the trial that the pain reduction was statistically significant in the cadexomer iodine group having either the superficial or deep ulcers. They further added that though quantitative bacteriologic studies were not performed, significant reductions of pus and debris occurred in the cadexomer group than the standard treatment group.
Cadexomer iodine added to the regimen of good hygiene, good nursing, and reduction of localized pressure results in more rapid cleansing and healing of decubitus ulcers, the authors concluded.
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. Brett DW. Cadexomer iodine: A fresh look at an old gem. WP&R Journal 2019; 27(1):42-48.
2. Sibbald RG, Leaper DJ, Queen D. Iodine made easy. Wounds Int 2011;(2)2:1–3.
3. Falanga V. Iodine-Containing Pharmaceuticals: A Reappraisal. Proceedings of the 6th European Conference on Advances in Wound Management. Macmillan Magazines Ltd. (Eds). London, UK, 1997; 1-3. 6.
4. 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.
5. Zaidi SRH, Sharma S. Decubitus Ulcer. [Updated 2020 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553107/
6. Bansal C, Scott R, Stewart D, Cockerell CJ. Decubitus ulcers: a review of the literature. Int. J. Dermatol. 2005 Oct;44(10):805-10.
7. Frank C, Bayoumi I, Westendorp C. Approach to infected skin ulcers. Can Fam Physician. 2005;51(10):1352-1359.
8. Ohtani T, Mizuashi M, Ito Y, Aiba S. Cadexomer as well as cadexomer iodine induces the production of proinflammatory cytokines and vascular endothelial growth factor by human macrophages. Exp Dermatol. 2007;16(4):318-323.
9. Moberg S, Hoffman L, Grennert ML, Holst A. A randomized trial of cadexomer iodine in decubitus ulcers. J Am Geriatr Soc. 1983;31(8):462-465.
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