Use of Cadexomer Iodine and Povidone Iodine in Wound management: A comparative review
Iodine is a highly effective topical antimicrobial that has been used clinically in the treatment of wounds for more than 170 years. It has a broad spectrum of antimicrobial activity with efficacy against bacteria, mycobacteria, fungi, protozoa and viruses and can be used to treat both acute and chronic wounds. (1) It is being considered an old gem in wound care management because of its antiseptic properties too. It is also relatively inexpensive and easy to use.
One of the first antiseptic iodine preparations to be used in wound care was Lugol's solution containing elemental iodine and potassium in water, which was developed in 1829. (2) This solution was also used to treat wounds in the American Civil War. Even nowadays, Iodine is one of the most widely used preparations used with popular formulations being povidone-iodine and cadexomer-iodine.
Povidone-iodine or polyvinylpyrrolidone iodine complex (PVP-I) is a combination of molecular iodine and polyvinylpyrrolidone surfactant/iodine complex. It is a water- soluble complex with elemental iodine bound to a synthetic polymer 10% solution in water. (3) In wound care, Povidone- iodine is available in a 7.5% concentration scrub with detergent for pre-operative and post- operative scrubbing and a germicidal wash, a 5% water-soluble first aid cream, and a 10% water- soluble ointment. The most commonly manufactured form is a 10% solution in water, for application as a paint, spray, or wet soak. (4)
On the other hand, Cadexomer iodine is an iodophor, which provides controlled release of iodine without cytotoxic effects. Cadexomer iodine is a long-established topical antimicrobial, which is used in the treatment of a variety of wounds. Its therapeutic efficacy is supported by a large body of clinical evidence. (5)
"Cadexomer iodine, carries iodine (0.9% weight/weight) immobilized in beads of dextrin and epichlorhydrin and has been demonstrated to be highly effective in promoting healing of exudative wounds", stated Zhao in his study on "Slow release iodine preparation and wound healing". His research examined the effects of varying concentrations of cadexomer iodine on the viability of human fibroblasts in culture and later concluded that cadexomer iodine has definite non-toxic concentration ranges for fibroblasts in vitro, which are consistent with a lack of cellular toxicity in human chronic exudative wounds treated with cadexomer iodine. Cadexomer iodine may also have the additional property of trapping microorganisms. (6)
Another review by Angel DE et al in 2008 laid an outline to examine the properties of iodine- based products in an attempt to provide an evidence-based structure to facilitate the choice of iodine-based product. They studied the effects of Povidone iodine and Cadexomer Iodine. In order to draw conclusions regarding the value of iodine- based products in wound care, the authors reviewed the results of both animal and human studies.
Povidone Iodine
A. Human studies:
Many studies were conducted over the years to study the effect on povidone- iodine on wound healing but out of them, many Human studies using povidone-iodine showed contradictory outcomes to each other. For instance-
1. Connell demonstrated a decrease in wound infection rates (11.9% to 6%) when povidone-iodine was eliminated from wound cleansing protocols on acute wounds requiring suturing in the emergency department (7) whereas Gordon et al. established an 18% rate of wound infection when povidone-iodine was used in a similar clinical setting. (8)
2. Conversely, Gravett et al. and Stringer et al. established that the use of povidone-iodine on patients prior to suturing lacerations reduced the incidence of wound infection.
3. Denning concluded that there was no significant difference in wound healing when dry dressing was compared to Povidone- iodine dressing.
4. However, Sindlear & Mason found there to be a decrease in wound infection rates when surgical wounds were irrigated with povidone-iodine post-operatively.
Although conflicting, the majority of human studies established the efficacy of povidone-iodine in reducing the bacterial load in both acute and chronic wounds however, there is a lack of evidence to determine if there is a positive or negative effect on wound healing.
B. Animal studies:
Numerous animal studies have been performed examining the effect of povidone-iodine on wound healing rates and the bacterial burden in wounds. Most researchers provide information regarding the reason for the type of animal used in their study together with the location and types of tissue of the animal used for wounding, and clearly describe methods and products used in treating the wounds. None of the animal studies examine the effect of povidone-iodine in chronic wounds, as an animal equivalent does not exist. (9)
Besides, conflicting evidence was demonstrated in several studies in the experimental pig model. (10) One such study is that of Archer et al where Povidone-iodine delayed wound healing and did not reduce bacterial growth. Other studies on animals reveal the following findings-
1. Rodeheaver et al. studied the effect of Povidone iodine in guinea pigs. The authors concluded that within the first 10 minutes of a single application of povidone-iodine there was a noteworthy decrease in the bacterial load.
2. Malloy & Brady used a rat model (n=50) with two incised full thickness wounds each comparing normal saline wick to povidone-iodine wicks and found that healing was delayed for 30 days in the povidone-iodine group.
3. Two studies have been conducted using mice both demonstrating impaired wound healing with use of povidone-iodine. (11),(12)
Cadexomer Iodine
Human studies:
Human clinical studies using cadexomer-iodine in chronic wounds such as diabetic foot ulcers, venous leg ulcers or pressure ulcers have demonstrated a positive effect on wound healing.
Jamie A Schwartz studied the in vivo effect of cadexomer iodine antibacterial dressing on diabetic foot ulcers (DFUs) that were infected or achieved a critical level of colonisation, looking specifically at wound progression in relation to bioburden and came to the conclusion that there was a median reduction of 53.6% in ulcer surface area and 50% in ulcer depth from baseline to final.
Moreover, the most commonly quoted study demonstrating the effectiveness of cadexomer- iodine is by Skog et al. where 93 patients with recalcitrant venous leg ulcers were studied. Patients were randomised to either cadexomer-iodine or one of various standard therapies. After 6 weeks of treatment with cadexomer-iodine, there was a 34% decrease in ulcer size compared with 5% in the other treatment groups.
Overall, it was learnt that cadexomer-iodine had a positive effect on wound healing, reducing the bacterial load and decreasing infections.
Discussion
With numerous studies producing different results in different scenarios, Angel et al stated while povidone iodine is mostly prescribed for ulcerative wounds, minor burns, and traumatic skin loss cadexomer iodine is prescribed in chronic exudative wounds where slough, infection, or the risk of infection is an issue
"Evaluation of the results of numerous in vivo studies demonstrate overwhelmingly that there is enough evidence to support the use of cadexomer-iodine in the chronic wound. The review mentioned that there is a lack of evidence to suggest that cadexomer-iodine would have a negative impact on wound healing and infection.
On the other hand, in the presence of infection, the application of povidone iodine proves to be effective at reducing bacteria numbers and decreasing wound infections.
Having said that Povidone-iodine impairs collagen synthesis, has a toxic effect on fibroblasts and keratinocytes, and impairs epithelial cell migration, therefore potentially having a detrimental effect on the healing process in non-infected human wounds. Steen conducted a review of the
literature to determine the effects of povidone-iodine in burn victims. He concluded that povidone-iodine should be used with caution on granulating or recently incised surgical tissue. (13)
Conclusion
Iodine has been shown to be an effective antiseptic; however, the use of iodine in wound management remains a contentious issue for clinicians amidst concerns for its efficacy and impact on wound healing. Cadexomer-iodine has a positive impact on healing in the chronic wound environment. The literature supports the use of povidone and cadexomer iodine in wound care for its effects on tissue and cells, especially in newer formulations. Cadexomer iodine has proven to be very effective in chronic wounds while povidone iodine has been noted to be more effective in infected acute wounds.(14)
The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Cadexomer Iodine, click here
References
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2. Hugo WB. A brief history of heat and chemical preservation and disinfection. J Appl Bacteriol 1991; 71: 9-18.
3. Khan NM. Antiseptics, iodine, povidone-iodine and traumatic wound cleansing. J Tissue Viability 2006; 16(4):6-10.
4. Kramer SA. Effect of povidone-iodine on wound healing: a review. J Vasc Nurs 1999; 17:17-23.
5. Brett DW. Cadexomer iodine: A fresh look at an old gem. WP&R Journal 2019; 27(1):42-48.
6. 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. doi:10.1046/j.1365- 2133.2002.04605.x
7. Connell S. A two-part quality assurance project addressing infection rates of wounds sutured in the emergency department. J Emerg Nurs 1991; 17:212-4
8. Gordon MWG, Aikman L, Little K et al. Prevention of wound infection in the accident and emergency department: does povidone-iodine dry powder spray reduce infection rates? Br J Accident Emerg Med 1989; 1989(4):11-13.
9. Drosou A, Falabella A & Kirsner RS. Antiseptics on wounds: an area of controversy. Wounds 2003; 15(5):149-166.
10. Mertz PM, Alvarez OM, Smerbeck RV et al. A new in vivo model for the evaluation of topical antiseptics on superficial wounds. Arch Dermatol 1984; 120:58-62.
11. Kashyap A, Beezhold D, Wiseman J et al. Effect of povidone-iodine dermatologic ointment on wound healing. Am Surg 1995; 61(6):486-491.
12. Kjoseth D, Frank JM, NBarker JH et al. Comparison of the effects of commonly used wound agents on epithelization and neovascularization. J Am Coll Surg 1994; 179:305-312.
13. Steen M. Review of the use of povidone-iodine (PVP-I) in the treatment of burns. Postgrad Med J 1993; 69(Suppl 3):S84-S92.
14. R Murdoch & K M Lagan (2013) The role of povidone and cadexomer iodine in the management of acute and chronic wounds, Physical Therapy Reviews, 18:3, 207-216, DOI: 10.1179/1743288X13Y.0000000082
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