Abstract
Background and Aims
Diabetic foot ulcers (DFU) are a severe complication in diabetes patients, often resulting in significant morbidity and mortality due to non‐healing. This study investigated the effectiveness of 5% topical potassium permanganate on these ulcers.
Methods
A clinical trial was conducted on 23 patients with Wagner grade I and II DFU. Patients in the control group received standard treatment, while those in the intervention group also received 5% potassium permanganate topically. Data were recorded at 0, 7, 14, and 21 days for analysis.
Results
Among 23 patients studied, 7 (30.4%) were male and 16 (43.7%) female, with an average age of 59 ± 4 years. Both groups showed a statistically significant decrease in wound size and infection over time (p < 0.001). The intervention group, however, had a more substantial reduction in wound size and infection rate (p < 0.05).
Conclusion
Potassium permanganate, when applied topically, is both well‐tolerated and effective in enhancing wound healing and reducing infection in DFU, suggesting its potential as a complementary treatment.
Keywords: diabetic, diabetic foot, foot, foot ulcer
1. INTRODUCTION
Diabetic foot ulcer (DFU), a serious complication of diabetes, frequently results in amputation, represents a major cause of hospitalization for diabetic patients, and is attributed to over half of non‐traumatic lower limb amputations. Over half of non‐traumatic lower limb amputations are due to DFUs, highlighting the gravity of this issue. 1 , 2
DFUs not only pose a threat to physical health, leading to increased frailty and reduced life expectancy but also impose a substantial financial burden on healthcare systems, particularly in low‐income countries. 3 , 4 , 5 , 6 In Iran, where the prevalence of diabetes exceeds the global average, finding cost‐effective treatments for diabetes‐related complications like DFUs is crucial. 7
Effective monitoring standards for DFUs encompass pressure redistribution, debridement of necrotic tissue, infection management, and revascularization of distal limb vessels. 8
However, these methods do not fully address the complex nature of DFU healing. Enter potassium permanganate (KMnO4), an oxidizing agent known for its antimicrobial properties and ability to promote wound healing. 9
KMnO4 is safe for topical use, environmentally stable, and aids in the formation of granulation tissue and collagen synthesis, essential for wound repair. Despite its potential benefits, including cost‐effectiveness, ease of application, and low patient risk, there is a lack of comprehensive research on KMnO4's effectiveness in treating DFUs. 10
This study aims to fill this gap by examining the topical application of a 5% potassium permanganate solution on DFUs. It seeks to determine whether KMnO4 can be a viable, affordable option in the management of DFU, especially in resource‐constrained settings.
2. METHODS
We conducted a randomized clinical trial to investigate the effects of topical KMnO4 on DFU. The study centered on diabetic patients presenting with at least one‐foot ulcer (either plantar or dorsal surface) and a Wagner score of one or two. Grade one is considered a full thickness involvement of the skin and grade two is when ulcer penetrates through skin, fat and ligaments and not bones. 11 Eligible participants were those with type 2 diabetes, aged 18−65 years, who sought care at Velayat Scar Clinic and displayed chronic neuropathic and nonischemic ulcers. We excluded participants with any ulcer side effects, those experiencing KMnO4‐related pain, individuals with progressive infections, or signs of pus, patients requiring debridement, those exhibiting ischemia in the lower limbs, and any with an ABI/TBI score below 0.7. A general surgeon executed the DFU diagnosis and patient selection.
Following the screening process, 23 qualifying patients entered the study at Velayat Scar clinic in 2022.
Ethics: Our trial adhered to the Declaration of Helsinki. The Institutional Review Board (IRB) of Guilan University of Medical Sciences sanctioned the protocol (IR.GUMS.REC.1401.292), and the Iranian Registry of Clinical Trials endorsed it on 02‐11‐2022 (registration reference: IR.GUMS.REC.1401.292). Every participant was briefed on the study's purpose, procedures, potential risks, and benefits. Written informed consent was mandatory for enrollment. We prioritized participants' privacy, ensuring data anonymization before analysis. The research team was versed in ethical conduct standards, and the IRB was promptly informed of any adverse or unforeseen events.
Patients were randomized into either the intervention or control group. While the control group received the standard DFU treatment (pressure reduction, daily cleaning of the DFU with soap and water, and daily ulcer assessment), 9 , 10 the intervention group also received topical KMnO4 solution, strictly applied to the ulcer and avoiding healthy skin. Patients were instructed to self‐administer the treatment daily. Apart from the standard DFU treatment, the control group received topical and systemic antibiotics in terms of infection, but no dressings were utilized.
The primary metric was ulcer length, gauged using an electronic caliper. Secondary measures encompassed local infection, scar healing (evaluated by a plastic surgeon), healing duration, demographics, fasting blood glucose, and HbA1C levels as a glycemic control indicator. A plastic surgeon performed weekly patient assessments, involving interviews, physical check‐ups, and ulcer digital photography. The treatment spanned 21 days, with tri‐weekly patient consultations.
We used restricted randomization (random allocation rule) for randomizing patients into treatment groups. In the process of random assignment, the analyst creates a random sequence, and one of the nurses assigns the patients to the intervention and control groups based on the entry and exit criteria in the study, and the project manager assigns the participants to the intervention and control groups based on a certain randomization method. To concealment, the concealment method of random allocation has been used. In this method, using identical sealed envelopes with a random sequence in such a way that each of the generated random sequences is recorded on a card, and the cards are placed inside the envelopes in order. To maintain the random sequence, the outer surface of the envelopes is numbered in the same order. At the time of starting the registration of eligible patients for the study, one of the envelopes will be opened in order, and the candidate patient will receive one of two types of treatment.
Patients were grouped using restricted randomization. Descriptive and inferential statistics analyzed the data. Tests for data normality included Kolmogorov−Smirnov and Shapiro−Wilk. Lune's test verified variance homogeneity. Depending on the assumptions met, we employed independent t‐tests, repeated measures tests, Mann−Whitney tests, Friedman tests, and Bonferroni corrections, among others. Qualitative data analyses used the χ 2 or Fisher's exact test. All analyses were conducted on SPSS version 28, with a significance threshold set at 0.05.
To monitor patient adherence to the trial, a trained nurse called the participants every day to check for the daily treatment and ask for any specific side effects.
3. RESULTS
From October 2022 to January 2023, we evaluated 41 patients, of whom 23 completed the trial (Figure 1). The patients' ages ranged from 48 to 65 years, with a mean age of 59.3 ± 4.5 years. Table 1 demonstrates that aside from HbA1c and scar duration, our results couldn't show significant differences in baseline characteristics between the groups. The main parameters were examined each week by the plastic surgeon, and the results are shown in Table 2.
Figure 1.
Patient selection.
Table 1.
Baseline characteristics.
| All | Intervention group | Control group | p Value | ||
|---|---|---|---|---|---|
| Age | Mean (SD) | 59.3 (4.5) | 59.7 (1.2) | 58.5 (1.4) | 0.60 |
| Sex | Female | 16 | 8 | 8 | 0.80 |
| Male | 7 | 4 | 3 | ||
| Hypertension | Positive | 13 | 6 | 7 | 0.43 |
| Negative | 10 | 6 | 4 | ||
| Dyslipidemia | Positive | 13 | 6 | 7 | 0.43 |
| Negative | 10 | 6 | 4 | ||
| Smoking | Positive | 10 | 6 | 4 | 0.43 |
| Negative | 13 | 6 | 7 | ||
| Duration of the disease (years) | Mean (SD) | 14 (6.3) | 12.8 (1.7) | 15.6 (1.1) | 0.29 |
| FBS | Mean (SD) | 198 (46.6) | 196 (12.3) | 200.1 (15.8) | 0.93 |
| HbA1c | Mean (SD) | 8.7 (1.2) | 8.1 (0.2) | 9.3 (0.3) | 0.05 |
| Scar duration (days) | Mean (SD) | 9.3 (3.3) | 10.7 (1) | 7.8 (0.7) | 0.05 |
| ESR | Mean (SD) | 21.5 (11.5) | 19.8 (2.8) | 23.1 (4.1) | 0.07 |
| WBC | Mean (SD) | 11,095.6 (2750.2) | 10,633.3 (494.2) | 11,600 (1082) | 0.85 |
Table 2.
Scar features during the trial.
| Day 0 | Day 7 | Day 14 | Day 21 | p Value a | ||
|---|---|---|---|---|---|---|
| Ulcer length (mm) | Intervention group | 239.9 (75.1) | 179.8 (25) | 115.8 (33.1) | 53.5 (33.8) | <0.001 |
| Control group | 372.1 (6) | 281.1 (18) | 204.9 (91.6) | 117.6 (45.1) | <0.001 | |
| p Value b | 0.012 | 0.020 | 0.024 | 0.006 | ||
| Wound infection | Intervention group | 66.7% | 8.3% | 0% | 0% | <0.001 |
| Control group | 72.7% | 63.6% | 36.4% | 0% | <0.001 | |
| p Valueb | 0.07 | 0.005 | 0.022 | ‐ | ||
Related‐samples Cochran's Q test.
Independent‐sample proportions test (Wald test).
In the intervention group, six patients had ulcers near the fingers and another six on the plantar foot surface. Conversely, the control group comprised four patients with finger ulcers and seven with plantar foot ulcers.
Both groups exhibited significant reductions in ulcer length. By the third session, the intervention group's mean ulcer length was notably less than that of the control group (p = 0.05). Furthermore, the intervention group consistently reported lower local infection rates than the control group (p = 0.03).
Relative wound healing improvements were evident in both groups on Days 7 and 14. By Day 21, 4 of 12 patients in the intervention group achieved complete wound healing, whereas none in the control group reported full recovery.
4. DISCUSSION
Potassium permanganate, a recognized oxidizing agent, has the ability to disrupt bacterial activity, particularly for anaerobes like clostridia. 12
Although it's been employed in wound management for years, its application for DFU remains under‐researched. However, a few recent studies, such as those by Chen et al. 10 and Rai, 13 have hinted at its potential, emphasizing the need for more conclusive research.
Our study, which primarily focused on a patient demographic of women with an average age of 59 years, confirms the therapeutic advantage of potassium permanganate in conjunction with standard treatment. Significant observations were the high prevalence of smoking among the participants and the increased incidence of hyperlipidemia (HLP) and hypertension (HTN)—both aligning with previously established findings, indicating the destructive effects of smoking on diabetic patients. 14 , 15 , 16 , 17 Given the metabolic syndrome's nature, where diabetes, HTN, and HLP often coexist, this observation is unsurprising. However, due to our study's limited sample size, this conclusion is specific to our study participants and cannot be broadly applied to the entire statistical population. Numerous independent studies have examined the prevalence of these diseases and their interrelationships, which was not a focus of our study.
KMnO4 offers several advantages, including its cost‐effectiveness, low sensitization at standard concentrations, high patient tolerance, and proven efficacy. 9 , 10 , 13 These implications matter as the study was conducted in a low‐income country, highlighting the importance of the cost‐effectiveness of treatments. Hence, the effectiveness and affordability of KMnO4 could be considered as a protocol for diabetic foot care in Iran's healthcare system. Compared to monotherapy, combination therapy of complex chronic DFUs with standard care and KMnO4 is well tolerated, enhances wound healing, and reduces infection.
The control and intervention groups exhibited similarities in various metrics, such as average age, gender ratio, and duration of diabetes, validating the effectiveness of our randomization process. However, there were noteworthy differences like the HbA1c level and the onset time of treatment post‐ulcer detection. HbA1c was significantly higher in the control group, indicating poor glycemic control, and patients in the control group started treatment on average 2 days later than the intervention group, which could introduce potential biases.
The average diabetes duration among patients was approximately 14 years, with no significant differences between the case and control groups. This duration is expected in patients with DFUs, as they often result from diabetic neuropathy and ischemia, which are chronic processes that take years to develop. Although not statistically significant, a longer disease duration may have influenced the control group's results, introducing a potential bias.
A notable outcome was the observed rapid wound healing among potassium permanganate users, with some even achieving full recovery within 21 days—results that mirror the findings of Delgado et al.'s study. 9
Yet, while our study aligns with current literature, it's paramount to consider external factors like smoking, HTN, and the duration of diabetes, which play crucial roles in ulcer progression and healing. Future research should aim to isolate and understand these variables better, ensuring a more comprehensive understanding of the treatment's potential. 18 Also, we believe that patient compliance in this treatment could be measured in future studies.
One of the participants in this trial showed skin irritation around the ulcer when applying KMnO4 for the first time. She was a 61‐year‐old woman, with a DFU of 26 mm length on the plantar surface of her foot. According to previous studies, 5% topical KMnO4 is highly tolerated for topical use. Adverse effects like irritation or hypersensitivity do not seem to be permanent and disappear when the application stops. 19 , 20
4.1. Limitations and strengths
In our study, we only evaluated DFUs with a Wagner score of 1 and 2 and did not assess other ulcer types. Additionally, we did not follow‐up with patients after the final visit on Day 21. The study sample size is small (23 patients), limiting the results' generalizability. A more significant number of cases is required to make a precise evaluation of the protocol's advantage. Higher HbA1c levels in the control group indicate poor glycemic control, which can be a source of bias in terms of response rate to the treatment. We recommend that future studies focus on more severe ulcers and extend the follow‐up period.
This study represents the first trial among DFUs in the Iranian population, and it raises evidence toward the effectiveness of KMnO4 in treating DFUs.
5. CONCLUSION
In conclusion, potassium permanganate, when paired with standard DFU treatment, shows promise in accelerating wound recovery. However, more expansive studies are needed to ascertain its full potential and applications.
AUTHOR CONTRIBUTIONS
Afrooz Haghdoost: Data curation; project administration; resources; supervision; writing—review and editing. Mohammadreza Mobayen: Conceptualization; methodology; project administration; supervision; validation. Iraj Baghi: Methodology; supervision; writing—review and editing. Zahra Haghani‐Dogahe: Data curation; formal analysis; investigation; methodology; project administration; writing—original draft; writing—review and editing. Reza Zarei: Data curation; software; visualization; writing—original draft. Amir Pirooz: Project administration; resources; supervision; validation. Heydar Ali Balou: Investigation; methodology; visualization. Alireza Feizkhah: Software; writing—original draft. All authors have read and approved the final version of the manuscript.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
TRANSPARENCY STATEMENT
The lead author, Zahra Haghani‐Dogahe, affirms that this manuscript is an honest, accurate, and transparent account of the study being reported, that no important aspects of the study have been omitted, and that any discrepancies from the study as planned (and if relevant, registered) have been explained.
ACKNOWLEDGMENTS
We thank the staff of Velayat Scar Clinic for their help and support.
Haghdoost A, Mobayen M, Baghi I, et al. Potassium permanganate in treatment of diabetic foot ulcer: a randomized clinical trial. Health Sci Rep. 2024;7:e2073. 10.1002/hsr2.2073
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. The corresponding author had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.
REFERENCES
- 1. Pérez‐Panero AJ, Ruiz‐Muñoz M, Cuesta‐Vargas AI, Gónzalez‐Sánchez M. Prevention, assessment, diagnosis and management of diabetic foot based on clinical practice guidelines: a systematic review. Medicine. 2019;98(35):e16877. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Chastain CA, Klopfenstein N, Serezani CH, Aronoff DM. A clinical review of diabetic foot infections. Clin Podiatr Med Surg. 2019;36(3):381‐395. [DOI] [PubMed] [Google Scholar]
- 3. Tuglo LS, Nyande FK, Agordoh PD, et al. Knowledge and practice of diabetic foot care and the prevalence of diabetic foot ulcers among diabetic patients of selected hospitals in the Volta Region, Ghana. Int Wound J. 2022;19:601‐614. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Ignatyeva VI, Severens JL, Ramos IC, Galstyan GR, Avxentyeva MV. Costs of hospital stay in specialized diabetic foot department in Russia. Value Health Reg Issues. 2015;7:80‐86. [DOI] [PubMed] [Google Scholar]
- 5. Kasiya MM, Mang'anda GD, Heyes S, et al. The challenge of diabetic foot care: review of the literature and experience at Queen Elizabeth Central Hospital in Blantyre, Malawi. Malawi Med J. 2017;29(3):218‐223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Game F. Choosing life or limb. Improving survival in the multi‐complex diabetic foot patient. Diabetes Metab Res Rev. 2012;28:97‐100. [DOI] [PubMed] [Google Scholar]
- 7. Mirzaei M, Rahmaninan M, Mirzaei M, Nadjarzadeh A, Dehghani Tafti AA. Epidemiology of diabetes mellitus, pre‐diabetes, undiagnosed and uncontrolled diabetes in Central Iran: results from Yazd health study. BMC Public Health. 2020;20:166. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Jeffcoate WJ, Vileikyte L, Boyko EJ, Armstrong DG, Boulton AJM. Current challenges and opportunities in the prevention and management of diabetic foot ulcers. Diabetes Care. 2018;41(4):645‐652. [DOI] [PubMed] [Google Scholar]
- 9. Delgado‐Enciso I, Madrigal‐Perez VM, Lara‐Esqueda A, et al. Topical 5% potassium permanganate solution accelerates the healing process in chronic diabetic foot ulcers. Biomed Rep. 2018;8(2):156‐159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Chen P, Carville K, Swanson T, et al. Australian guideline on wound healing interventions to enhance healing of foot ulcers: part of the 2021 Australian evidence‐based guidelines for diabetes‐related foot disease. J Foot Ankle Res. 2022;15(1):1‐24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. PN VC, PP P, LJM T, AH T. Comparison of wifi, University of Texas and Wagner classification systems as major amputation predictors for admitted diabetic foot patients: a prospective cohort study. Malays Orthop J. 2020;14(3):114‐123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Shaabani A, Tavasoli‐Rad F, Lee DG. Potassium permanganate oxidation of organic compounds. Synth Commun. 2005;35(4):571‐580. [Google Scholar]
- 13. Rai V. What is the evidence for the use of potassium permanganate for wound care? Drug Ther Bull. 2020;58(5):71‐74. [DOI] [PubMed] [Google Scholar]
- 14. Pellaton C, Kubli S, Feihl F, Waeber B. Blunted vasodilatory responses in the cutaneous microcirculation of cigarette smokers. Am Heart J. 2002;144:269‐274. [DOI] [PubMed] [Google Scholar]
- 15. Rossi M, Pistelli F, Pesce M, et al. Impact of long‐term exposure to cigarette smoking on skin microvascular function. Microvasc Res. 2014;93:46‐51. [DOI] [PubMed] [Google Scholar]
- 16. Xia N, Morteza A, Yang F, Cao H, Wang A. Review of the role of cigarette smoking in diabetic foot. J Diabetes Investig. 2019;10(2):202‐215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Liedberg E, Persson BM. Age, diabetes and smoking in lower limb amputation for arterial occlusive disease. Acta Orthop Scand. 1983;54:383‐388. [DOI] [PubMed] [Google Scholar]
- 18. Rodrigues BT, Vangaveti VN, Urkude R, Biros E, Malabu UH. Prevalence and risk factors of lower limb amputations in patients with diabetic foot ulcers: a systematic review and meta‐analysis. Diabetes Metabolic Syndrome: Clin Res Rev. 2022;16(2):102397. [DOI] [PubMed] [Google Scholar]
- 19. Hu N, Wu X, Liu R, et al. Novel application of vacuum sealing drainage with continuous irrigation of potassium permanganate for managing infective wounds of gas gangrene. J Huazhong Univ Sci Technol [Medical Sciences]. 2015;35:563‐568. [DOI] [PubMed] [Google Scholar]
- 20. Biswas M, Gibby O, Ivanova‐Stoilova T, Harding K. Cushing's syndrome and chronic venous ulceration: a clinical challenge. Int Wound J. 2011;8:99‐102. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. The corresponding author had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.