ADVERTISEMENT
Medical Mythology, Misconceptions, and Misinformation: Does Iodine Impede Wound Healing?
Abstract
Introduction. PI has been shown to be effective against a broad spectrum of bacteria and to be cytotoxic to a variety of cell types. Such findings led to the widespread belief that PI interferes with wound healing. Objective. This article reviews laboratory studies, animal wound studies, and clinical studies that examine the efficacy and safety of iodine-based wound products in wound healing. Methods. The authors searched PubMed and Scopus databases without time restrictions, and 62 articles were selected for complete evaluation. Fourteen RCTs and 5 comparative studies that evaluated PI and 15 RCTs that evaluated CI were included. Results. In 63% (n = 12) of the PI studies, there was no difference between PI and controls and in 5% (n = 1) PI performed significantly better than the comparator. In 31% (n = 6), outcomes were better with controls than with PI. In the RCTs on CI, 64% (n = 9) of the studies found no difference between CI and controls. Thirty-five percent (n = 5) showed significantly positive influence of CI compared with controls. Conclusions. Both CI and PI appear to be safe, with no evidence that these products impede wound healing, are associated with more infections, or require more amputations compared with other modalities. PI can effectively be used for short periods of time, and CI is an effective wound care modality for chronic wounds.
Abbreviations
CI, cadexomer iodine; DFU, diabetic foot ulcer; PI, povidone-iodine; PU, pressure ulcer; RCT, randomized controlled trial; SOC, standard of care; VLU, venous leg ulcer.
Introduction
Iodine is an antiseptic that has been used in various forms for more than 150 years.1 Early preparations caused local pain and tissue irritation.2 To avoid these unwanted side effects, iodine carriers (iodophors) were created.1 In iodophors, iodine is carried in a detergent that acts as a reservoir for iodine. Four types of such carriers are polyoxymer iodophors, cationic surfactant iodophors, nonionic surfactant iodophors, and polyvinyl-pyrrolidone iodophors (also known as PI).1
PI is the most common form of iodine used in clinical practice and has been available since 1955.2 It is chemically bound as triiodide and is available as a solution, aerosol spray, ointment cream, and foam dressing.1 The most common commercially available form of PI is 10% solution in water, yielding 1% available iodine (Betadine; Atlantis Consumer Healthcare, Inc).2,3
Another commonly used form of iodine is CI, which was released in 1981.1 This preparation consists of cadexomer starch biodegradable spherical hydrophilic beads (size range, 100 µm–315 µm) mixed with 0.9% iodine of cadexomer starch, which incorporates 0.9% iodine.4 In contrast to PI, CI products are widely accepted because the iodine is more slowly released and is thought to be less cytotoxic.
The use of iodine to manage wounds is controversial. Many health care professionals have closely held beliefs that iodine damages wounds and impedes wound healing, but they often do not know the foundation of or evidence for this belief. This medical mythology affects clinical behavior. The goal of the current study was to review laboratory studies, animal wound results, and clinical studies on the efficacy and safety of iodine-based wound products in wound healing, and to determine if clinical evidence demonstrates that CI or PI impedes wound healing.
Methods
The authors searched PubMed and Scopus databases without time restrictions, using the following search terms: “iodine,” “betadine,” “cadexomer iodine,” “Iodosorb,” “povidone iodine,” “diabetic foot ulcer,” “venous leg ulcer,” “wounds,” and “randomized clinical trial.” The search included human and animal studies. A total of 15 146 articles were identified. The authors reviewed abstracts for eligible studies. Retrospective studies, articles for which the authors could not access the data in its entirety, and articles that did not evaluate PUs, DFUs, and venous stasis ulcers or surgical wounds were excluded. A total of 62 articles were identified for complete evaluation. Those studies were then divided into in vitro studies, animal studies, human studies, and RCTs of PI and CI. The authors identified 14 RCTs and 5 comparative studies that evaluated PI and 14 RCTs that evaluated CI.
Results
In 63% (n = 12) of the PI studies, there was no difference between PI and controls; in 5% (n = 1), PI performed significantly better than the comparator. In 31% (n = 6), outcomes were better with controls than with PI. In the RCTs on CI, 64% (n = 9) of the studies found no difference between CI and controls. Thirty-five percent (n = 5) showed significantly positive influence of CI compared with controls.
Many of the perceptions about the effectiveness or problems with iodine seem to be based on in vitro research. The good and bad of PI centers around the bactericidal effects balanced by concerns of cytotoxicity to specific cell lines associated with wound healing. Iodine has well-established broad-spectrum bactericidal activity. PI has been shown to be effective against gram-positive and gram-negative bacteria such as methicillin-resistant Staphylococcus aureus, S aureus, Escherichia coli, Stenotrophomonas maltophilia, Serratia marcescens, Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus.5-12 There are similar data to suggest that CI is effective against gram-positive and gram-negative bacteria, including streptococci, enterococci, Enterobacteriaceae such as Proteus and Klebsiella species, P aeruginosa, S aureus, and methicillin-resistant S aureus.4,13,14
However, information from in vitro studies raised concerns about PI cytotoxicity. This is the reason some clinicians do not use iodine-based products. To the authors’ knowledge, the earliest study that reported cell damage from PI is a bench study from 1947 by Farkas,15 which evaluated the toxicity of bromine and iodine on human leukocytes and their effect on phagocytosis. Farkas15 reported that iodine appeared more harmful to this process compared with bromine. Subsequent studies demonstrated that iodine had a detrimental effect on lymphocytes, granulocytes, monocytes, fibroblasts, and keratinocytes.15-20 For instance, Van den Broek et al17 investigated various concentrations of PI on granulocytes and monocytes. They found that the number of dead granulocytes and monocytes increased in concentrations greater than 0.005%. Tatnall et al21 found concentrations of PI greater than 0.004% to be 100% toxic to keratinocytes. Lineaweaver et al18 reported a significant decrease in fibroblast survival in cultures with concentrations of 0.025% sodium hypochlorite (0% fibroblast survival), 0.25% acetic acid (74% fibroblast survival), 0.05% PI (50% fibroblast survival), and 0.03% hydrogen peroxide (41% fibroblast survival). Fabreguette et al20 reinforced these findings by demonstrating that PI at therapeutic concentrations was cytotoxic to fibroblasts and keratinocytes. These cytotoxic effects on cells that are fundamental to wound healing may be the reason many clinicians believe wound healing is adversely affected by iodine.
In contrast, basic science evidence demonstrates that CI is not cytotoxic to cells; rather, it appears to have a positive effect on the cells involved in the wound healing process. This is attributed to the slower release of iodine. Both Zhou et al22 and Brustolin et al23 reported that CI was not cytotoxic to fibroblasts. In 1995, Schmidt et al24 demonstrated that CI modulated fibroblast proliferation and inhibited superoxide generation by macrophages. This finding was reinforced in 1997, when Moore et al25 demonstrated that CI modulates cytokine induction in human macrophages. While these bench studies revealed evidence for the cytotoxic effect of iodine on tissue in vitro, such findings do not directly correlate to clinical outcomes; evaluation of translational and clinical studies was required to answer this question.
Interestingly, the concerns raised regarding PI cytotoxicity do not appear to translate to impaired wound healing in animal models or in human studies. Several animal studies do not support the hypothesis that PI impairs wound healing. Niedner26 reported that concentrations of up to 10% PI did not inhibit granulation tissue formation or the epithelialization process, as demonstrated in animal studies on beagles, rats, rabbits, and guinea pigs. These findings were supported by an earlier study by Gruber et al27 that investigated 3% hydrogen peroxide, 10% PI, and 0.25% acetic acid, with saline as a control. That study found no significant difference in the mean healing times in split-thickness and full-thickness wounds in Sprague-Dawley rats treated with acetic acid (12.0 days and 18.6 days, respectively), PI (12.2 days and 19.2 days, respectively), and saline (12.4 days and 19.5 days, respectively). Split-thickness and full-thickness wounds treated with hydrogen peroxide healed significantly faster (10.2 days and 17.0 days, respectively) than controls (12.4 days and 19.5 days, respectively) (P < .05).27 Arai et al28 evaluated the rate of reepithelialization in a rabbit ear wound model in which wounds were managed with PI. When residual PI remained on the wound, reepithelialization was inhibited (P < .05). However, when the PI was removed, there was no difference between rinsed wounds and wounds treated with only a wet dressing. Kjolseth et al29 evaluated the effects of bacitracin, 0.25% sodium hypochlorite, 0.5% silver nitrate, 1% silver sulfadiazine, 8.5% mafenide acetate, and 10% PI on the rate of wound epithelialization and neovascularization in 99 circular full-thickness wounds in mouse ears. Epithelialization occurred significantly faster in wounds treated with silver sulfadiazine (mean ± standard deviation, 7.1 days ± 0.3) and mafenide acetate (7.3 days ± 0.3) than in wounds treated with PI (11.8 days ± 0.55), sodium hypochlorite (approximately 10.5 days), or bacitracin (approximately 10 days) (P < .01). Epithelialization was slowest in wounds treated with PI. However, wound neovascularization was fastest in wounds treated with PI and silver sulfadiazine (15.0 days ± 0.4 and 15.3 days ± 0.7, respectively), which was significantly faster than wounds treated with silver nitrate (18.4 days ± 0.56; P < .05), sodium hypochlorite (approximately 18 days), or bacitracin (approximately 17 days).29
Mulliken et al30 evaluated the tensile strength of wounds soaked in PI in a rat model. They evaluated incised dorsal wounds that were soaked in 1% PI or lactated Ringer solution for 15 minutes prior to closure. Tensile strength was evaluated at 1, 2, and 6 weeks. They found no significant difference in tensile strength between the incised wounds with PI compared with the control group at any time point.30 Cytotoxicity has been reported in in vitro studies; however, based on in vivo studies in animal wound models it is reasonable to conclude that, compared with other common wound treatments, PI does not affect neovascularization, wound healing, time to healing, or tensile strength.
Similarly, the available animal studies on CI demonstrate positive effects on healing and no deleterious effects. In 1998, Lamme et al31 published their findings on the use of CI ointment in full-thickness wounds in pigs. CI was compared with saline. Those authors did not observe any negative effects of CI ointment on the formation of granulation tissue, neovascularization, or wound contraction. This result was reinforced in 2012 by Brustolin et al,23 who evaluated the effects of CI, sodium chloride, and distilled water on 53 wounds in 36, 6-mm punch lesions in Wistar rats. There were no differences in the 3 treatment groups in terms of granulation tissue, neovascularization, or wound contraction. Although in vitro models were concerning for cytotoxic effects of PI, in vivo animal models have not shown convincing evidence of a negative effect on wound healing.
The current study also investigated whether the findings of animal wound studies translate to clinical outcomes in humans. Clinical studies were evaluated in 2 treatment groups. Human studies were divided into 2 groups: patients treated with PI solution, ointment, or foam (Table 132-50), and patients treated with CI (Table 251-64). The authors identified 14 RCTs and 5 comparative studies that examined the efficacy of PI on wound healing. In addition, the authors identified 14 RCTs that examined the efficacy of CI, with 2 on DFUs, 1 on PU, and 11 on VLUs. One study analyzed all 3 wound types.
Among studies that used PI products, 8 evaluated DFUs, 1 evaluated surgical wounds, 5 evaluated VLUs, 3 evaluated PUs, and 2 evaluated wounds of various etiologies. The majority of PI studies (63%, n = 12) demonstrated no difference between the comparator and PI. One study evaluating dextranomer versus PI showed PI performed significantly better than the comparator. Only 31% (n = 6) of the studies demonstrated a better result with SOC or a comparator. Table 132-50 highlights the outcomes of the PI studies. There are no animal or human studies that reported increased size or depth of wounds, or an increase in infections when PI was used. In most of the human studies included in the current study (63%), there was no significant difference in clinical outcomes between PI and the comparator. In 35% of the human studies, comparator treatment resulted in significantly more wounds healed or faster healing.
It is important to note that in many of these studies, PI served as the control group. For instance, Kajagar and Joshi32 compared negative pressure wound therapy with PI. Five studies of DFU compared PI with honey. Three of the studies demonstrated statistical difference in outcomes and the other 2 demonstrated no statistical difference. Parimala and Rani50 completed a comparative VLU study assessing the net wound healing score and they found there was no statistical difference between honey and PI (16.6 ± 3.3 and 18.2 ± 3.2, respectively; P > .05). Gulati et al49 in 2014 evaluated honey versus PI and demonstrated a significant improvement in the percent healed at 6 weeks (31.8% vs 0% PI; P < .01). Shukrimi et al40 also demonstrated no difference in time to healing between honey (14.4 days) and PI (15.4 days) (P > .05). In contrast, Ur-Rehman et al38 demonstrated a significantly greater percent wound area reduction at 15 days with honey compared with iodine (80.8% vs 54.6%; P < .001), and Yadav et al37 reported that patients treated with honey healed significantly faster than patients treated with PI (18 days and 28 days, respectively; P < .001).
Kajagar and Joshi32 compared negative pressure wound therapy with PI. As expected, the use of negative pressure wound therapy resulted in significantly greater mean wound area reduction (P = .029). Kaya et al42 reported that patients with PU managed with hydrogel had a significantly greater incidence of healed wounds compared with patients treated with PI (84% and 54%, respectively; P = .04). Imamura and Imura44 found no difference in the incidence of healed wounds at 8 weeks in patients treated with PI sugar paste compared with lysozyme ointment (21% [15/72] and 17% [12/69], respectively; P > .05). Fumal et al,45 Smith et al,46 and Kuznetsov et al48 found no difference in VLUs treated with PI and SOC or other interventions. The available evidence indicates that PI is a safe modality for wound management.
In RCTs of CI in wound management, the majority of studies (64% [n = 9]) found no significant difference between CI and comparator treatment. The remaining studies demonstrated positive effects of CI (35% [n = 5]). Further, a meta-analysis by Woo et al4 compared pooled RCT data and reported that wounds treated with CI were greater than 2 times more likely to heal compared with wounds treated with SOC (P < .0001). The authors of the current study identified 1 study that compared CI and PI. Gupta et al33 compared CI and PI in the management of wounds of various etiologies, including venous, arterial, diabetic, traumatic, and infected wounds. The wounds were evaluated every 2 days for 6 days. There was a significant reduction in mean wound area in both groups (CI, 189.4 cm2 ± 58.7 to 159.0 cm2 ± 58.4, and PI, 190.9 cm2 ± 76.3 to 174.2 cm2 ± 77.1; P < .05); however, there was no significant difference between the PI and CI groups. Gupta et al33 concluded that both CI and PI are safe in the management of wounds. Further, there are no animal or human studies that report increased size or depth of wounds, or an increase in infections when CI was used.
Discussion
Although in vitro studies of PI have raised concern for cytotoxicity, PI appears to be a safe modality. Both in vivo animal wound studies and human studies of acute and chronic wounds showed no evidence that iodine-containing products impede wound healing, result in more infections, or require more amputations. The question is whether the overall weight of the evidence of animal and human wound healing studies is convincing for the use of iodine-containing products. Often there is no translation from bench research to clinical practice, and there is an overreaction to either endorse or reject an approach that has no clinical evidence. The available evidence suggests that PI and CI are helpful in eradicating bacteria and reducing bioburden. Meta-analyses indicate that wounds treated with CI are twice as likely to heal as wounds treated with SOC.4 Although there is evidence that both PI and CI reduce bioburden, there is little evidence that either prevents wounds from becoming clinically infected.34,35 There was no difference in iodine-based treatments compared with SOC or other interventions in most of the studies analyzed in the current review.
In 31% of the PI studies included in this review, the comparator outperformed PI. In current clinical practice, PI tends to be reserved for short periods of time in wound management (eg, immediately postoperatively in a contaminated wound or in a wound complicated by surgical dehiscence). There were 9 CI studies (64%) that found no significant difference in patients treated with CI versus the comparator. The remaining studies demonstrated positive effects of CI (35% [n = 5]). The available evidence supports the use of CI in chronic wounds, often post-debridement in the management of chronic lower extremity ulcerations.
Limitations
This study has several limitations. The studies included are heterogenous in many ways that make accurate comparisons difficult. In addition, the studies use different operational definitions of success, such as wound healing, time to healing, percent wound area reduction, and rate of healing. The classic primary outcome in RCTs of ulcers is the proportion of wounds that heal in 12 to 16 weeks. This is the primary outcome in only 52.6% (n = 10) of the PI studies and in 78.6% (n = 11) of the CI studies included herein. In addition, many of the studies are small and do not have a power analysis or sample size justification. It is nearly impossible to show a significant difference in very small studies. The number of subjects in each treatment arm is less than or equal to 40 in 68.4% of the PI studies and 71.4% of the CI studies. The duration of most studies is variable. Most of the PI and CI studies (79% [n = 15] and 57% [n = 8], respectively) are less than or equal to 8 weeks’ duration. Finally, the etiology of wounds is variable and includes DFUs, VLUs, PUs, and surgical wounds. The CI studies are larger than the PI studies and have better outcomes. One outcome missing from many of the CI RCTs evaluated in the current study is infection as an adverse event.
One argument for using either PI or CI is that they kill broad-spectrum bacteria, which would also result in faster healing and fewer infections. It is not clear, however, if laboratory data on the bactericidal properties of PI and CI translate to fewer clinical infections and elimination of bioburden, with resulting improved wound healing. History suggests that such data do not translate. The authors of the current study identified only 2 studies that reported infection as an outcome in PI RCTs. In both cases, there was no difference in the incidence of infection between PI and the control.34,35 One misconception about products with reported antibacterial properties in the laboratory is that such data rarely translate to reduced infections in clinical practice and it is difficult to know if this is in fact the case with PI and CI.
Conclusions
Both CI and PI appear to be safe, and there is no evidence that these products impede wound healing or that they are associated with more infections or a need for more amputations compared with other wound healing strategies. PI can effectively be used for short periods of time, and CI is an effective wound care modality for chronic wounds.
Acknowledgments
Authors: Christopher Girgis, DPM; Mehmet A. Suludere, MD; P. Andrew Crisologo, DPM; and Lawrence A. Lavery, DPM, MPH
Affiliations: University of Texas Southwestern Medical Center, Department of Plastic Surgery, Dallas, TX
ORCID: Crisologo, 0000-0002-5367-9235;
Lavery, 0000-0002-7920-9952
Disclosure: The authors disclose no financial or other conflicts of interest.
Correspondence: Christopher Girgis, DPM; University of Texas Southwestern Medical Center, Department of Plastic Surgery, 5323 Harry Hines Blvd F4.310, Dallas, TX 75390; girgisdpm@gmail.com
Manuscript Accepted: August 21, 2023
References
1. Cooper RA. Iodine revisited. Int Wound J. 2007;4(2):124-137. doi:10.1111/j.1742-481X.2007.00314.x
2. Sneader W. Drug Discovery: A History. John Wiley and Sons; 2005: 68.
3. Burks RI. Povidone-iodine solution in wound treatment. Phys Ther. 1998;78(2):212-218. doi:10.1093/ptj/78.2.212
4. Woo K, Dowsett C, Costa B, Ebohon S, Woodmansey EJ, Malone M. Efficacy of topical cadexomer iodine treatment in chronic wounds: systematic review and meta-analysis of comparative clinical trials. Int Wound J. 2021;18(5):586-597. doi:10.1111/iwj.13560
5. Bigliardi P, Langer S, Cruz JJ, Kim SW, Nair H, Srisawasdi G. An Asian perspective on povidone iodine in wound healing. Dermatology. 2017;233(2-3):223-233. doi:10.1159/000479150
6. Kunisada T, Yamada K, Oda S, Hara O. Investigation on the efficacy of povidone-iodine against antiseptic-resistant species. Dermatology. 1997;195(suppl 2):14-18. doi:10.1159/000246025
7. Yasuda T, Yoshimura Y, Takada H, et al. Comparison of bactericidal effects of commonly used antiseptics against pathogens causing nosocomial infections. Part 2. Dermatology. 1997;195(suppl 2):19-28. doi:10.1159/000246026
8. Hedberg M, Miller JK. Effectiveness of acetic acid, betadine, amphyll, polymyxin B, colistin, and gentamicin against Pseudomonas aeruginosa. Appl Microbiol. 1969;18(5):854-855. doi:10.1128/am.18.5.854-855.1969
9. Houang ET, Gilmore OJ, Reid C, Shaw EJ. Absence of bacterial resistance to povidone iodine. J Clin Pathol. 1976;29(8):752-755. doi:10.1136/jcp.29.8.752
10. Berkelman RL, Holland BW, Anderson RL. Increased bactericidal activity of dilute preparations of povidone-iodine solutions. J Clin Microbiol. 1982;15(4):635-639. doi:10.1128/jcm.15.4.635-639.1982
11. Kanagalingam J, Feliciano R, Hah JH, Labib H, Le TA, Lin JC. Practical use of povidone-iodine antiseptic in the maintenance of oral health and in the prevention and treatment of common oropharyngeal infections. Int J Clin Pract. 2015;69(11):1247-1256. doi:10.1111/ijcp.12707
12. Eggers M, Koburger-Janssen T, Ward LS, Newby C, Muller S. Bactericidal and virucidal activity of povidone-iodine and chlorhexidine gluconate cleansers in an in vivo hand hygiene clinical simulation study. Infect Dis Ther. 2018;7(2):235-247. doi:10.1007/s40121-018-0202-5
13. Fitzgerald DJ, Renick PJ, Forrest EC, et al. Cadexomer iodine provides superior efficacy against bacterial wound biofilms in vitro and in vivo. Wound Repair Regen. 2017;25(1):13-24. doi:10.1111/wrr.12497
14. Roche ED, Woodmansey EJ, Yang Q, Gibson DJ, Zhang H, Schultz GS. Cadexomer iodine effectively reduces bacterial biofilm in porcine wounds ex vivo and in vivo. Int Wound J. 2019;16(3):674-683. doi:10.1111/iwj.13080
15. Farkas H. Tissue toxicity of the germicides iodine and bromine. Proc Soc Exp Biol Med. 1947;66(1):207-209. doi:10.3181/00379727-66-16038
16. Ninnemann JL, Stein MD. Suppressor cell induction by povidone-iodine: in vitro demonstration of a consequence of clinical burn treatment with betadine. J Immunol. 1981;126(5):1905-1908.
17. Van den Broek PJ, Buys LF, Van Furth R. Interaction of povidone-iodine compounds, phagocytic cells, and microorganisms. Antimicrob Agents Chemother. 1982;22(4):593-597. doi:10.1128/AAC.22.4.593
18. Lineaweaver W, Howard R, Soucy D, et al. Topical antimicrobial toxicity. Arch Surg. 1985;120(3):267-270. doi:10.1001/archsurg.1985.01390270007001
19. Lineaweaver W, McMorris S, Soucy D, Howard R. Cellular and bacterial toxicities of topical antimicrobials. Plast Reconstr Surg. 1985;75(3):394-396. doi:10.1097/00006534-198503000-00016
20. Fabreguette A, Zhi Hua S, Lasne F, Damour O. Evaluation of the cytotoxicity of antiseptics used in current practice on cultures of fibroblasts and keratinocytes. Article in French. Pathol Biol (Paris). 1994;42(9):888-892.
21. Tatnall FM, Leigh IM, Gibson JR. Comparative study of antiseptic toxicity on basal keratinocytes, transformed human keratinocytes and fibroblasts. Skin Pharmacol. 1990;3(3):157-163. doi:10.1159/000210865
22. 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
23. Brustolin EV, Skare TL, Nassif PA, et al. Wound healing under the effect of iodine cadexomer in rats. Acta Cir Bras. 2012;27(12):874-879. doi:10.1590/s0102-86502012001200008
24. Schmidt RJ, Kirby AJ, Chung LY. Cadexomer iodine formulations may modulate the redox environment of wounds. In: Iodine and Wound Physiology. Information Transfer Ltd, 1995:6.1-6.26.
25. Moore K, Thomas A, Harding KG. 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(1):163-171. doi:10.1016/s1357-2725(96)00128-8
26. Niedner R. Cytotoxicity and sensitization of povidone-iodine and other frequently used anti-infective agents. Dermatology. 1997;195(suppl 2):89-92. doi:10.1159/000246038
27. Gruber RP, Vistnes L, Pardoe R. The effect of commonly used antiseptics on wound healing. Plast Reconstr Surg. 1975;55(4):472-476.
28. Arai K, Yamazaki M, Maeda T, Okura T, Tsuboi R. Influence of various treatments including povidone-iodine and healing stimulatory reagents in a rabbit ear wound model. Int Wound J. 2013;10(5):542-548. doi:10.1111/j.1742-481X.2012.01016.x
29. Kjolseth D, Frank JM, Barker JH, et al. Comparison of the effects of commonly used wound agents on epithelialization and neovascularization. J Am Coll Surg. 1994;179(3):305-312.
30. Mulliken JB, Healey NA, Glowacki J. Povidone-iodine and tensile strength of wounds in rats. J Trauma. 1980;20(4):323-324. doi:10.1097/00005373-198004000-00007
31. Lamme EN, Gustafsson TO, Middelkoop E. Cadexomer-iodine ointment shows stimulation of epidermal regeneration in experimental full-thickness wounds. Arch Dermatol Res. 1998;290(1-2):18-24. doi:10.1007/s004030050271
32. Kajagar BM, Joshi K. Efficacy of vacuum-assisted closure therapy versus conventional povidone iodine dressing in the management of diabetic foot ulcers: a randomized control trial. Int J Health Sci Res. 2017;7(5):47-51.
33. Gupta S, Shinde RK, Shinde S. Comparison of the outcomes of cadexomer iodine and povidone-iodine ointments in wound management. Cureus. 2022;14(5):e24667. doi:10.7759/cureus.24667
34. Jeffcoate WJ, Price PE, Phillips CJ, et al. Randomised controlled trial of the use of three dressing preparations in the management of chronic ulceration of the foot in diabetes. Health Technol Assess. 2009;13(54):1-86, iii-iv. doi:10.3310/hta13540
35. Jurczak F, Dugre T, Johnstone A, Offori T, Vujovic Z, Hollander D, Group AASTWS. Randomised clinical trial of Hydrofiber dressing with silver versus povidone-iodine gauze in the management of open surgical and traumatic wounds. Int Wound J. 2007;4(1):66-76. doi:10.1111/j.1742-481X.2006.00276.x
36. Gwak HC, Han SH, Lee J, et al. Efficacy of a povidone-iodine foam dressing (Betafoam) on diabetic foot ulcer. Int Wound J. 2020;17(1):91-99. doi:10.1111/iwj.13236
37. Yadav AK, Dwivedi S, Desai S. A comparative study in between tropical honey and povidone dressing in diabetic wounds in a medical college of Northern India. Int Surg J. 2018;5(10):3391-3393. doi:10.18203/2349-2902.isj20184095
38. Ur-Rehman E AM, Ali A, Qureshi A-RZ-U-R, Rashid M. Comparison between honey and povidone-iodine/normal saline dressing for management of Wagner’s grade I & II diabetic foot ulcers. Pakistan J Med Health Sci. 2013;7(4):1082-1085.
39. Khandelwal S, Chaudhary P, Poddar DD, Saxena N, Singh RA, Biswal UC. Comparative study of different treatment options of grade III and IV diabetic foot ulcers to reduce the incidence of amputations. Clin Pract. 2013;3(1):e9. doi:10.4081/cp.2013.e9
40. Shukrimi A, Sulaiman AR, Halim AY, Azril A. A comparative study between honey and povidone iodine as dressing solution for Wagner type II diabetic foot ulcers. Med J Malaysia. 2008;63(1):44-46.
41. Agarwal H, Gupta, AK, Gupta, N, Mukharjee S, Durga CK. Comparison of results of silver-impregnated dressing with povidone iodine based-dressing in patients with diabetic foot. Hellenic J Surg. 2015;87:465-467.
42. Kaya AZ, Turani N, Akyüz M. The effectiveness of a hydrogel dressing compared with standard management of pressure ulcers. J Wound Care. 2005;14(1):42-44. doi:10.12968/jowc.2005.14.1.26726
43. Nisi G, Brandi C, Grimaldi L, Calabrò M, D’Aniello C. Use of a protease-modulating matrix in the treatment of pressure sores. Chir Ital. 2005;57(4):465-468.
44. Imamura S, Imura Y. The clinical effect of KT-136 (sugar and povidone-iodine ointment) on decubitus ulcers: a comparative study with lysozyme ointment. Jpn Pharmacol Ther. 1989(17):255-280.
45. Fumal I, Braham C, Paquet P, Piérard-Franchimont C, Piérard GE. The beneficial toxicity paradox of antimicrobials in leg ulcer healing impaired by a polymicrobial flora: a proof-of-concept study. Dermatology. 2002;204(suppl 1):70-74. doi:10.1159/000057729
46. Smith JM, Doré CJ, Charlett A, Lewis JD. A randomized trial of biofilm dressing for venous leg ulcers. Phlebol J Venous Dis. 1992;7(3):108-113. doi:10.1177/026835559200700307
47. Groenewald JH. The treatment of varicose stasis ulcers: a controlled trial. Schweiz Rundsch Med Prax. 1981;70(28):1273-1278.
48. Kuznetsov NA, Rodoman GV, Nikitin VG, Karev MA, Shalaeva TI. The use of current bandages in the treatment of patients with venous trophic ulcers of the skin: clinical and economic aspects. Article in Russian. Khirurgiia (Mosk). 2009(11):63-69.
49. Gulati S, Qureshi A, Srivastava A, Kataria K, Kumar P, Ji AB. A prospective randomized study to compare the effectiveness of honey dressing vs. povidone iodine dressing in chronic wound healing. Indian J Surg. 2014;76(3):193-198. doi:10.1007/s12262-012-0682-6
50. Parimala PJ, Rani SR. A comparative study on the effect of honey and povidone iodine ointment on pain, wound healing and quality of life of patients with varicose ulcer. J Med Sci Clin Res. 2014;2(6):1500-1509.
51. Raju R, Kethavath SN, Sangavarapu SM, Kanjarla P. Efficacy of cadexomer iodine in the treatment of chronic ulcers: a randomized, multicenter, controlled trial. Wounds. 2019;31(3) 85-90.
52. 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 Derm Venereol. 1996;76(3):231-235. doi:10.2340/0001555576231235
53. Miller CN, Newall N, Kapp SE, et al. A randomized-controlled trial comparing cadexomer iodine and nanocrystalline silver on the healing of leg ulcers. Wound Repair Regen. 2010;18(4):359-367. doi:10.1111/j.1524-475X.2010.00603.x
54. Lindsay G LD, Lyons KGB. A study in general practice of the efficacy of cadexomer iodine in venous leg ulcers treated on alternate days. Acta Ther. 1986;12:141-148.
55. Kero M TK, Hollmen A, Pekanmaki K. A comparison of cadexomer iodine with dextranomer in the treatment of venous leg ulcers. Current Therapeutic Res. 1987;42(5):761-7.
56. Moss C TA, Shuster S. Comparative study of cadexomer iodine and dextranomer in chronic leg ulcers. Scottish Med J. 1984;25:54.
57. 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(9):360-364.
58. Steele K, Irwin G, Dowds N. Cadexomer iodine in the management of venous leg ulcers in general practice. Practitioner. 1986;230(1411):63-68.
59. 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. doi:10.1111/j.1532-5415.1983.tb05117.x
60. 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(6):428-435. doi:10.1177/030006058801600604
61. Holloway Jr GA, Johansen KH, Barnes RW, Pierce GE. Multicenter trial of cadexomer iodine to treat venous stasis ulcer. West J Med. 1989;151(1):35-38.
62. Hansson C. The effects of cadexomer iodine paste in the treatment of venous leg ulcers compared with hydrocolloid dressing and paraffin gauze dressing. Cadexomer Iodine Study Group. Int J Dermatol. 1998;37(5):390-396. doi:10.1046/j.1365-4362.1998.00415.x
63. Ormiston MC, Seymour MT, Venn GE, Cohen RI, Fox JA. Controlled trial of Iodosorb in chronic venous ulcers. Br Med J (Clin Res Ed). 1985;291(6491):308-310. doi:10.1136/bmj.291.6491.308
64. 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(1):77-83. doi:10.1111/j.1365-2133.1983.tb03995.x
Current Issue
Sign Up Today
