|Year : 2021 | Volume
| Issue : 2 | Page : 148-150
Randomized control trial to assess the efficacy of superoxide solution on wound healing
Ajith John George1, Cecil T Thomas1, Vasanth Mark Samuel1, Pranay Gaikwad1, Srujan Lam Sharma1, Emmanuel Lazarus1, Vimalin Samuel2
1 Department of General Surgery Unit 1, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of Vascular Surgery, Christian Medical College, Vellore, Tamil Nadu, India
|Date of Submission||30-Jul-2020|
|Date of Decision||07-Sep-2020|
|Date of Acceptance||18-Sep-2020|
|Date of Web Publication||13-Apr-2021|
Ajith John George
Department of General Surgery Unit 1, Christian Medical College, Vellore, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Introduction: Chronic wounds are the bane of any healthy population, with widespread economic and mental repercussions. Various techniques have been described to improve wound healing which includes the debridement of unhealthy tissue, saline, sodium hypochlorite (Daikin's) solution dressings. Newer techniques described include silver-based solutions and superoxide gel solutions. Methods: The study was a double-blinded randomized control trial. Randomization was done on the same limb of each donor site. The sample size was 16 in each arm. All patients undergoing STSG were randomized into two groups, one receiving the superoxide gel solution to one random half of the wound and the other group receiving only regular dressings. The donor site was analyzed on Day 5, 7, and 9. The assessor was blinded from the solution used. The difference in the rate of healing, with time to epithelialization and granulation, was assessed. Results: The mean time to epithelialization in the superoxide gel group was 6.75 days and in the non-gel group was 8.35 days. The mean difference was 1.60 days, which was statistically significant. The mean time to granulation in the superoxide gel group was 5.89 days and in the non-gel group was 6.60 days. The mean difference was 0.71 days, which was not statistically significant. The intraclass correlation coefficient (ICC) was 0.699. Conclusion: There was a significant and faster rate of epithelialization in the superoxide gel group. A superoxide gel solution is a cheaper method to improve the rate of healing.
Keywords: Epithelialization, granulation, split-thickness skin graft, superoxide solution
|How to cite this article:|
George AJ, Thomas CT, Samuel VM, Gaikwad P, Sharma SL, Lazarus E, Samuel V. Randomized control trial to assess the efficacy of superoxide solution on wound healing. Indian J Vasc Endovasc Surg 2021;8:148-50
|How to cite this URL:|
George AJ, Thomas CT, Samuel VM, Gaikwad P, Sharma SL, Lazarus E, Samuel V. Randomized control trial to assess the efficacy of superoxide solution on wound healing. Indian J Vasc Endovasc Surg [serial online] 2021 [cited 2021 Jun 24];8:148-50. Available from: https://www.indjvascsurg.org/text.asp?2021/8/2/148/313552
| Introduction|| |
Venous ulcers are the bane of the modern society. The burden of venous, diabetic, and other nonhealing ulcers increases patient morbidity and increases hospital stay. The main aim of the treatment of an ulcer or wound is to decrease the microbiological load in the tissue, to increase the rate of healing, minimize disability, and prevent recurrence. Various techniques that have been described to improve wound healing include debridement of unhealthy tissue, dressings such as alginate, skin graft, topical creams, hyperbaric oxygen therapy, negative pressure wound therapy, and electromagnetic or ultrasound therapy. Newer techniques include silver-based solutions and superoxide solutions.
In the current study, we tested the hypothesis that a superoxide gel could improve the rate of wound healing. Microdacyn superoxide gel is a Class 2B medical device containing a stabilized, pH neutral, hypotonic solution of reactive-oxidizing species, including hypochlorous acid, peroxide, ozone, and superoxide. Superoxide gel contains 30 ppm hypochlorous acid, 40 ppm sodium hypochlorite, sodium chloride, and other oxidative species. Superoxide hydrogel contains 80 ppm hypochlorous acid, 20 ppm sodium hypochlorite, sodium chloride, sodium magnesium fluorosilicate, sodium phosphate plus other oxidative species. The predominant oxidizing agents include free chlorine, ozone, hypochlorous acid, and hydrogen peroxide.
Superoxide gels have demonstrated potent antimicrobial efficacy against a wide range of bacteria, viruses, fungi, molds, spores, biofilms, and simple eukaryotes. It exerts this potent antimicrobial effect by the oxidative disruption of the outer membrane followed by rapid osmotic rupture and is therefore not susceptible to the development of microbial resistance.
As a first step in assessing the efficacy of superoxide gel, we decided to use split-thickness skin graft (STSG) donor sites to assess healing rates. Split-thickness skin grafting is a widely used reconstructive technique for the replacement of damaged or missing skin caused by burns, trauma, surgical resection for cancer, and chronic wounds. Split-thickness autografts are harvested by excising the epidermis and part of the dermis. Donor-site wounds generally heal by re-epithelialization in 7–14 days. Various studies have been done on STSG donor sites, including assessing wound healing with silver, collagen, and other colloids.
We decided to study the effect of superoxide gel on STSG donor sites before the direct use on wounds to confirm safety and efficacy in physiologically normal areas of skin. Using a donor site for wound healing is an accepted mode of study as mentioned above.
| Methods|| |
The present study was initiated once cleared from the institutional review board and ethics committee. The present study was registered with the Clinical Trials Registry of India. This study was a double-blinded, randomized control trial. It was in adherence to the 2010 CONSORT guidelines. The present study was conducted at the Department of Surgery Unit 1, Christian Medical College, Vellore, India. This study was eligible for patients undergoing split-thickness grafting with donor sites more than 10 cm × 10 cm. Randomization was done on the same limb of each donor site. A sample size of 16 patients in each limb was calculated with the following formula: N = 2 standard deviation (SD)2 (Z alpha + Z beta) 2/(Mean 1 − Mean 2) 2. (SD = Longest − Shortest/4, SD = 10 − 5/4 = 1.25; Longest time to healing – 10 days and shortest – 5 days; Z alpha = 1.96, Z beta = 0.84).
All patients except those with burns wounds and skin diseases were included. All patients undergoing STSG were randomized into two groups, one receiving the superoxide gel solution to one random half of the wound and the other group receiving only regular saline dressings. Randomization was computer generated into the upper and lower halves of the donor site [Figure 1]. This randomization was concealed within a sealed envelope and was known by one member of the surgical team. All the other team members were blinded including the assessors. The superoxide gel was colorless and odorless and hence would be impossible to notice any difference. A minimum of 10 cm × 10 cm area of the donor site was required. With preoperative consent and randomization, the superoxide gel was applied to either the upper or lower aspects of the wound. The site, which was not sprayed with a superoxide gel, was covered by a sterile towel to prevent cross-contamination of solutions. The superoxide gel was applied from a distance of 5–10 cm. Paraffin-based gauze was applied. A sterile towel was then removed, and paraffin-based gauze was applied to the nonsprayed site after cleaning with 0.9% normal saline solution. Two separate identical dressings were done.
|Figure 1: The split-thickness skin graft donor site divided into the upper and lower half, divided approximately in the middle|
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The donor site was analyzed on the postoperative day 5, 7, and 9 [Figure 2]. The primary objective was to assess the earliest time to granulation and epithelialization. The assessor was blinded from the solutions used. Poststudy, the difference in the rate of healing was assessed. Pictures of the donor sites were taken and were assessed once the data were completed. The pictures were evaluated by three independent assessors. The assessors would look for the earliest onset of granulation and epithelialization.
|Figure 2: Donor site divided into two. The upper half was randomized for a superoxide solution. Demarcation noted with increased granulation and epithelialization in the upper half of the donor site|
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The data were entered in Excel 2010, and the analysis was completed from the IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. (Armonk, NY: IBM Corp.). t-tests, paired t-test analysis, and interclass coefficient ratio were analyzed.
| Results|| |
A total of 16 donor sites were inspected. All patients had received the intervention with no loss of patients. All patients were included in continuity. The exclusion criteria were for those with burns or any skin disease. None of the patients were excluded. The high definition pictures were analyzed once the sample size was completed [Figure 3]. There was a definite difference between the control and study arm.
|Figure 3: Three examples of donor sites before the assessment by a blinded team of consultants|
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The mean age was 42 years, ranging from 16 to 66 years. There were 13 males and 3 females. Thirty-seven percent (6 patients) were primarily operated for an oral malignancy, 50% (8 patients) for a previous necrotizing soft-tissue infection with a large raw surface, and 13% (2 patients) for skin malignancy.
The mean time to epithelialization in the superoxide gel group was 6.75 days (SD = 1.01 days) and in the nongel group was 8.35 days (SD = 0.71 days). The mean difference was 1.60 days, which was statistically significant ( P = 0.05; 95% confidence interval [CI] = 0.97–2.20).
The mean time to granulation in the superoxide gel group was 5.89 days (SD = 0.95 days) and in the nongel group was 6.60 days (SD = 1.08 days). The mean difference was 0.71 days, which was not statistically significant ( P = 0.59; 95% CI = −0.02–1.44).
We had used the average score from three consultants to assess the earliest evidence of epithelialization. These scores were compared to each other and had an intraclass correlation coefficient (ICC) of 0.699 when analyzed for average scores.
| Discussion|| |
Superoxide gel is noncytotoxic and demonstrates significant wound healing through the enhancement of fibrocyte, keratinocyte migration, mast cell stabilization, and angiogenic reperfusion. These solutions have demonstrated superior wound healing versus other traditional antimicrobials such as saline, povidone-iodine, chlorhexidine, benzoyl peroxide, and systemic antibiotics. Superoxide solutions have been included in the antibiotics guidelines for some countries which the World Health Organization has acknowledged.
Bongiovanni had concluded that it is one of the greatest advancements in venous ulcer care. Hypochlorous acid kills pathogens within 30 s of action and with active capillary dilation, there is increased arterio-venous shunting and an increase in TcpO2 levels. Kapur and Marwaha had shown the earlier appearance of granulation and epithelialization in comparison to povidone iodine. Various uses of superoxide solutions have been shown in peritoneal lavage, wound healing in diabetic foot ulcer, venous foot ulcer, and decrease in Methicillin-resistant Staphylococcus aureus infections among burns patients.,,
The various confounding factors during the study were with different depths grafts that may exist with handheld STSG devices. This may be interpreted differently. There could have been a confounding or added influence of the gel form of superoxide solution. This could have aided wound healing.
In our study, we have shown a significant decrease in time to epithelialization, in other words, quicker healing times. The time to granulation was not significant. The interpretation was validated with ICC values with moderate reliability.
| Conclusions|| |
Superoxide in the gel form is effective in improving epithelialization and enhancing wound healing, as compared to normal saline. This is the first step in proving its effectiveness in the treatment of diabetic and venous ulcers. This is a cheap and effective modality to enhance wound healing.
Financial support and sponsorship
This study was financially supported by the Institution Review Board of CMC, Vellore.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]