Product POINTERS

Use of iodine as topical cleanser on wounds is still controversial

By Liza G. Ovington, PhD, CWS
President, Ovington & Associates
Ft. Lauderdale, FL

Long known and used as a highly efficient disinfectant for inanimate surfaces and as a broad-spectrum topical antiseptic for intact skin, iodine still generates controversy when used as a cleansing solution or topical antiseptic for open wounds. There are numerous sources of both in vitro (meaning literally "in glass" or in a laboratory experiment) and in vivo (meaning literally "in life" or in a living system) data about the effects of iodine on bacteria and on animal tissues or human tissues and cells. These data are often conflicting and confusing.

Pure or elemental iodine is a solid material that looks like purple or black crystals. Solid iodine is fairly uncommon, evaporates readily as corrosive purple fumes, and is highly irritating to the skin, eyes, and mucous membranes. The solid form of iodine is rarely encountered except by the laboratory chemist. Aqueous or alcoholic solutions of iodine are more common in everyday usage.

Iodine is just barely soluble in water — only about one-third of a gram of iodine will dissolve in one liter of water at room temperature. One way iodine can be rendered water-soluble is by chemically complexing it to a readily water-soluble material. The complex of iodine and a water-soluble material is called an iodophor. Iodophors dissolve in water and then release very small amounts of free iodine, which are responsible for antibacterial activity. Iodophors are sometimes called "tamed iodine." One of the most common (and most controversial) iodophors is povidone-iodine, which is iodine complexed with a polyvinyl pyrrolidine polymer. Most of the data concerning the effects of iodine on wound healing have been generated using povidone-iodine.

Povidone-iodine is available in several forms, including an aqueous solution, an ointment, a cream, and a surgical scrub that includes a detergent. There are lab data to suggest that the antibacterial activity of the cream and the ointment formats is less than the aqueous solution or the scrub solution. The cream and ointment formulations have not been studied extensively in human chronic wounds. However, the existing data from animal studies and acute wounds in volunteers suggest that the vehicle portion of both products may have positive effects on healing. There have been both in vivo and in vitro studies of povidone-iodine solution and scrub that have demonstrated toxicity to cells such as fibroblasts, red blood cells, and neutrophils, as well as detrimental effects on wound breaking strength and capillary circulation. Toxicity of the povidone-iodine scrub has been attributed primarily to the detergent ingredient.

Studies focus on acute wounds, not chronic ones

Critics of these latter studies say animal data and data from cells in culture do not correlate with the human wound environment or experience with iodine. They cite other clinical studies where overall results of iodine usage in human wounds did not significantly delay healing. However, it should be noted that most of these studies have been carried out in acute wounds (such as surgical incisions, burns, and skin graft donor sites) as opposed to chronic wounds. The healing challenge presented by chronic wounds usually is different from (and more difficult than) the challenge presented by acute wounds. This is because chronic wounds have an underlying causative pathology as well as multiple factors contributing to delayed healing, such as poor nutrition or impaired blood supply.

There are relatively few studies of the use of povidone-iodine in chronic wound healing by secondary intention. One study in pressure ulcers compared the effects of silver sulfadiazine (SSD), povidone-iodine solution, and saline gauze on reducing bacterial bioburden as determined via quantitative tissue biopsy.1 The investigators found that SSD was 100% effective at keeping the tissue bioburden below 105 (wound infection is often defined as greater than 105 organisms in the tissues), saline gauze was 79% effective, and povidone-iodine was only 64% effective.

The majority of the other studies of the use of iodine in chronic wounds have examined the effects of a different iodophor: cadexomer iodine. Cadexomer iodine is a unique complex of iodine with a starch-based polymer (cadexomer). The starch molecule has been modified so it is a hollow, perforated sphere. The iodine molecules, which are larger than the starch molecule’s perforations, are encapsulated inside the sphere. Imagine the starch molecule as a Whiffle ball and the iodine as marbles inside. The starch molecules are absorbent; as they absorb fluid, they expand, and the perforations get larger. Eventually, the perforations are large enough for small amounts of the iodine molecules to escape.

It is this free iodine that is responsible for the documented antibacterial effects of the product. It has been shown that as the cadexomer iodine complex absorbs wound exudate, a concentration gradient of free iodine is created such that the lowest concentrations are at the wound surface. As the iodine leaves the cadexomer spheres, wound exudate, debris, and bacteria are taken up inside. A benefit of this iodophor, beyond antibacterial activity, is that it also acts as an absorbent product and may assist in autolytic debridement. The cadexomer can absorb up to six times its weight in wound fluid and organic matter from the wound.

The wound healing effects of this particular iodophor have been studied in nine randomized controlled trials. The majority of the studies targeted venous leg ulcers2-8; however, diabetic foot ulcers and pressure ulcers were addressed in two of the trials.9,10 Overall, these clinical studies in chronic wounds have consistently shown that the cadexomer iodine product is not only effective at reducing bacterial counts in the wound; it also appears to positively affect the healing process when compared to standard treatments (usually gauze and saline) and to the cadexomer starch vehicle alone. Noted effects are increased rate of granulation, epithelialization, and debridement; reduced exudate; and patient reports of reduced pain. Cadexomer iodine has shown effectiveness against methicillin-resistant Staphylococcus aureus in an animal model11 and against Pseudomonas aeruginosa in a venous leg ulcer clinical trial.12

Regarding potential adverse effects, in several studies, a few patients reported a transient burning sensation in the wound upon application of the cadexomer iodine. The literature also revealed two case reports of hyperthyroidism when the cadexomer was used on fairly large (8 cm2 and 12 cm2) leg ulcers in elderly patients.13

A laboratory study of the mechanism by which the cadexomer iodine product may be enhancing the healing process suggests it may be macrophage-mediated. In vitro cultures of human macrophages were co-cultured with the cadexomer iodine, cadexomer iodine-conditioned media, or free iodine in the presence of bacterial lipopolysaccharide and monitored for cytokine production. The investigators found that all three conditions stimulated the macrophages to produce inflammatory cytokines (TNF alpha and IL6). It is postulated that such an increase in production of these cytokines in a wound may result in a local influx of monocytes and lymphocytes that subsequently triggers a healing response.14

Cadexomer iodine may at last be a truly "tamed iodine" for use in chronic wounds to control bacteria and provide additional beneficial effects on the wound management process.

Cadexomer iodine is known commercially as Iodosorb Gel or Iodoflex Pad (a form that is more putty-like in consistency and moldable). It is distributed in the U.S. by HealthPoint Medical. Telephone: (800) 441-8227. Web site: www.healthpoint.com.

References

    1. Kucan JO, Robson MC, Heggers JP, Ko F. Comparisons of silver sulfadiazine, povidone iodine and physiologic saline in the treatment of chronic pressure ulcers. J Amer Geriatr Soc 1981; 29:232-235.

    2. Hansson C. The effects of cadexomer iodine in the treatment of venous leg ulcers compared with hydrocolloid dressing and paraffin gauze dressing. Int J Dermatol 1998; 37:390-396.

    3. Holloway GA, et al. Multicenter trial of cadexomer iodine to treat venous stasis ulcer. West J Med 1989; 151:35-38.

    4. 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.

    5. Steele K, Irwin G, Dowde N. Cadexomer iodine in the management of venous leg ulcers in general practice. Practitioner 1986; 230:63-68.

    6. 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.

    7. Ormiston MC, et al. Controlled trial of Iodosorb in chronic venous ulcers. Br Med J (Clin Res Ed) 1985; 291:308-310.

    8. Skog E, et al. A randomized trial comparing cadexomer iodine and standard treatment in the outpatient management of chronic venous ulcers. Br J Dermatol 1983; 109:77-83.

    9. Apelqvist J, Ragnarson 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 Derm Venereol 1996; 76:231-235.

    10. Moberg S, Hoffman L, Grennart ML, Holst A. A randomized trial of cadexomer iodine in decubitus ulcers. J Am Geriatr Soc 1983; 31:462-465.

    11. Mertz PM, Oliveira-Gandia MF, Davis SC. The evaluation of a cadexomer iodine wound dressing on methicillin-resistant Staphylococcus aureus in acute wounds. Dermatol Surg 1999; 25:89-93.

    12. Danielsen L, Cherry GW, Harding K, Rollman O. Cadexomer iodine in ulcers colonized by Pseudomonas aeruginosa. J Wound Care 1997; 6:169-172.

    13. Michanek A, et al. Iodine-induced hyperthyroidism after cadexomer treatment of leg ulcers. Lakartidningen 1998; 95:5,755-5,756.

    14. Moore K, Thomas A, Harding K. Iodine released from the wound dressing Iodosorb modulates the secretion of cytokines by human macrophages responding to bacterial lipopolysaccharide. Int J Biochem Cell Biol 1997; 29:163-171.