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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 32  |  Issue : 4  |  Page : 1272-1276

Evaluation of the effect of ozone therapy in diabetic foot ulcers


1 Department of General Surgery, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of General Surgery, Kafr El-Dawar General Hospital, Kafr El-Dawar, Beheira, Egypt

Date of Submission20-Jan-2019
Date of Decision12-Feb-2019
Date of Acceptance16-Feb-2019
Date of Web Publication31-Dec-2019

Correspondence Address:
Ahmed S Sadaawy Baghid
Damanhour, Beheira
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_20_19

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  Abstract 


Objectives
The objective of this study was to evaluate the effect of local ozone as an adjuvant therapy in patients with diabetic foot ulcers.
Background
Diabetes mellitus is a major problem that results in complications such as infections, gangrene, amputation, coma, and death. Diabetic foot ulcer can be treated by many methods; recently, ozone has been used in their treatment.
Patients and methods
A prospective cross-sectional study was conducted at Menoufia University Hospital and Moustafa Kamel Military Hospital for the treatment of foot ulcer. Sixty patients were selected on clinical, laboratory, and radiological bases. They were divided into 39 patients who had complete healing, 13 patients who had partial healing, and eight patients had no healing. All patients received two sets of local ozone therapy weekly for 10 weeks. They were evaluated for degree of healing and followed-up for 8 weeks after the end of therapy for healing.
Results
There were no significant differences between the studied groups with regard to age, sex, and type of diabetes. There was a significant reduction in the length of treatment and size of the ulcer in the healing group. Most of our patients showed complete healing (65%) and 21.6% showed partial healing, while only 13.4% showed nonhealing. Only 11.4% of cases of complete healing recurred.
Conclusion
The use of local ozone therapy markedly improves healing of diabetic foot ulcers with low incidence of recurrence.

Keywords: diabetes mellitus, diabetic foot ulcer, hyperbaric oxygen therapy, ozone therapy


How to cite this article:
Albatanony AA, El-Khateep YM, Sadek SA, Baghid AS. Evaluation of the effect of ozone therapy in diabetic foot ulcers. Menoufia Med J 2019;32:1272-6

How to cite this URL:
Albatanony AA, El-Khateep YM, Sadek SA, Baghid AS. Evaluation of the effect of ozone therapy in diabetic foot ulcers. Menoufia Med J [serial online] 2019 [cited 2020 Apr 4];32:1272-6. Available from: http://www.mmj.eg.net/text.asp?2019/32/4/1272/274231




  Introduction Top


Diabetes mellitus (DM) is a major problem that results in many complications such as retinopathy, blindness, nephropathy, renal failure and cardiovascular complications, diabetic foot infections, gangrene, amputation, diabetic coma, and death [1],[2],[3]. Classifications of diabetic foot ulcers can be made according to wound depth, presence of infection, and presence of peripheral arterial occlusive disease in a wider sentence. Diabetic foot disease may be infective, ischemic, or neuropathic [4],[5]. Diabetic foot ulcer can be treated by debridement, appropriate antibiotics, nonweight bearing, and vascular surgery [6]. Diabetic neuropathy and peripheral arterial disease are usually the major factors involved in diabetic foot ulcers. These two factors may act alone, together, or in combination with other conditions that limit joint mobility and increase susceptibility to infection [7]. Persons with DM have a 15–25% chance of developing a diabetic foot ulcer during their lifetime [8]. There are newer techniques for treatment of diabetic foot ulcers, such as bioengineered tissue, platelet-derived growth factor, and the use of hyperbaric oxygen therapy and the use of ozone therapy [9],[10]. Ozone is a strong antioxidant. It can exert protective effects by oxidative preconditioning, stimulating, and/or preserving the endogenous antioxidant systems and by blocking the xanthine/xanthine-oxidase pathway for reactive oxygen species' generation, as demonstrated in studies of the damage induced by carbon tetrachloride or by hepatic and renal ischemic perfusion [11],[12]. Ozone has been used with good results in treatment of patients with diabetic foot, because of its germicidal properties and its influence on the processes of oxygen metabolism and other effects [13],[14]. Ozone is a gaseous molecule consisting three oxygen atoms. Ozone is an unstable molecule in contrast to the stable oxygen molecule. Ozone therapy is systematically effective when pathological and immunological processes are activated. There are ischemic and infectious conditions such as macular degeneration due to aging in these wound-healing processes [15]. The aim of this study was to evaluate the effect of local ozone as an adjuvant therapy in patients with diabetic foot ulcers.


  Patients and Methods Top


A prospective cross-sectional study was conducted at Menoufia University Hospital and Moustafa Kamel Military Hospital for the treatment of foot ulcer. Sixty patients were selected on clinical, laboratory, and radiological bases. All patients were divided into: 39 patients who had complete healing, 13 patients who had partial healing, and eight patients who had no healing. All patients were selected during the period spanning from April 2017 to April 2018. All patients received local ozone therapy in the pain management unit at Menoufia University Faculty of Medicine. Patients' selection for the study was based on clinical diagnosis, laboratory investigations, plain radiography, and Duplex ultrasounds.

Inclusion criteria

Clean diabetic foot ulcer with no clinically evident infection, ulcers that presented after at least 3 months and not responding to treatment by conventional methods, and cases of controlled diabetes.

Ethical consideration

The study was approved by the ethical committee of Menoufia Faculty of Medicine and an informed consent was obtained from all patients' guardians before the study was commenced. Patients' grouping: group I included 39 diabetic foot ulcer patients with complete healing. Group II included 13 diabetic foot ulcer patients with partial healing. Group III included eight diabetic foot ulcer patients with nonhealing. The patients in the study received two sets of local ozone therapy weekly for 10 weeks and were then evaluated for the degree of healing. All patients received different concentrations of local ozone gas, which was controlled by an ozone apparatus. Before the ozone treatment, the ulcer was cleaned by saline and antiseptic solution and the foot was put in a plastic bag and exposed to ozone gas for about 30 min. The covering bag was left for 1–2 h; thereafter the ulcer was covered by sterile dressing. During follow-up of cases of the study, the following data were recorded: the degree of healing at the end of 10 weeks, which was judged by an independent consultant for documenting one of the following – complete healing, partial healing, or nonhealing; any complications of the ulcer were detected as spread of infection and/or gangrene. Cost of the procedure was also estimated. Moreover, patients were followed-up for 8 weeks after the end of therapy for healing.

Statistical analysis

The results were tabulated and statistically analyzed by using a personal computer using Microsoft Excel 2016 and SPSS, version 21 (SPSS Inc., Chicago, Illinois, USA). Statistical analysis was carried out using descriptive statistics – for example, percentage, mean and SD. Analytical statistics included the χ2 and paired t tests. A value of P less than 0.05 was considered statistically significant.


  Results Top


There was no significant difference between the studied groups with regard to the age (P = 0.231), whereas there was a significant increase in the age of the nonhealing group compared with the complete and partial healing groups (P = 0.012 and 0.01, respectively), and in sex distribution (P = 0.310, 0.241 and 0.352, respectively). Moreover, there was a statistically significant predominance of type I DM in the nonhealing group (P = 0.01 and 0.01, respectively). However, there was no significant difference between complete healing and partial healing groups with regard to type of DM (P = 0.21) and the period of previous treatment. Furthermore, the statistical analysis revealed a marked reduction in the length and width of the ulcers in cases of complete healing (P = 0.01). All patients of the complete healing, partial healing, and nonhealing groups had no signs of infection in their ulcers during a period of 6 months before therapy. Moreover, 13 (26%) of the whole patients had necrotic tissue in the floor of their ulcers, and 37 (74%) had no necrotic tissue in the floor of their ulcers. In addition, six (17.1%) of the patients with complete healing had necrotic tissue in the ulcer floor, and 29 (82.9%) had no necrotic tissue in their floors, while six patients of those with partial healing (6/13, 46.2%) had necrotic tissue in their floors. In addition, one (50%) patient of the nonhealing group had necrotic tissue in the floor of its ulcer, and the other had no necrotic tissue in the floor of his ulcer [Table 1].
Table 1: Comparison between the studied groups with regard to age, period of previous treatment, diabetes mellitus types, and ulcer criteria

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Further, during the period of applications of ozone, we give the patients empirical therapy in the form of an antibiotic (Averozolid), an analgesic (Cataflen 50 mg), and antifungal (Miconaz-H cream) therapy, and with the progress of therapy. These drugs reduced significantly in cases of complete-healing ulcers (P = 0.01), and, in partial-healing patients, these drugs were reduced but not in a significant manner. However, in nonhealing patients, these drugs either increased or were replaced with other effective drugs compared with those drugs on which the patients were started (P = 0.021) [Table 2]. Moreover, the use of local ozone therapy two sets weekly for 10 weeks markedly improves the healing of diabetic foot ulcers, as shown in [Figure 1], [Figure 2], [Figure 3].
Table 2: Effect of ozone therapy on the associated therapies in patients of the study

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Figure 1: A case of complete healing before therapy (a) and after therapy (b).

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Figure 2: A case of partial healing before therapy (a) and after therapy (b).

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Figure 3: A case of nonhealing before therapy (a) and after therapy (b).

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  Discussion Top


Ulcers as a complication of diabetes are commonly encountered in medical practice. Hospitals around the world treat patients with diabetic ulcers on a daily basis [16]. This was a cross-sectional prospective study of 50 cases of diabetic foot ulcer admitted to the Surgical Department at Menoufia University Hospital and Moustafa Kamel Military Hospital. Our study revealed that there was a significant increase in the age of the nonhealing group of patients, and this was due to the ischemic changes in those patients. Mohammad [17] found that the peak age of patients was in the sixth decade of life, which was in agreement with the age of our patients. The results of this study revealed that there was no statistical difference between the studied groups with regard to sex. Mohammad [17] found that female patients (71.3%) were more common than male patients (28.7%), which is in contradiction with our results. Moreover, Borrelli and colleagues revealed that the mean age of patients was 70 years, which was in agreement with our results. However, they found a male predominance in their study, which contradicts our results [9]. Sureda et al. [18] reported that the mean age of patients was 65.8 years, which was in agreement with our results. However, they reported a male predominance, which disagreed with our results [18]. Moreover, most of our patients were of type II DM (54%), with no significant predominance of type of DM. The study conducted by Mariam et al. [19] found that patients with type II DM were 2.58 times more likely to develop diabetic foot ulcer than those who had type I DM, which is in disagreement with our results [19]. In addition, our results revealed no significant difference between patients with regard to the length of previous treatment period. In this study, application of local ozone for the treatment of diabetic foot ulcer revealed a significant reduction in the length and width of the ulcer in cases of complete healing and partial healing, with marked reduction in the necrotic tissue in the floor of these ulcers. Liu et al. [15] documented that there was one trial that proved the positive effect of the use of ozone on reducing the length and size of the diabetic foot ulcer, which was in agreement with our results, while there were another two trials that proved there was no apparent difference in the size and length of diabetic foot ulcer when using local ozone therapy, which contradicts our results [15]. Furthermore, Travagli et al. [20] believe that applications of ozone accelerated wound closure in a young population due to oxygen tension by ozone in the surrounding wound area that acts as an antibacterial substance to decrease bacterial infection, and this goes side by side with our results [20]. Moreover, our study revealed a marked increase in the number of complete or partial-healing patients (96%) with minor nonhealed ulcers, and the recurrence rate was so low. Liu J et al. [15] found that the overall results of ozone therapy were excellent to good (72.3%), with the minority of patients experiencing a poor outcome (9.5%), and this coincides with our results. Borrelli et al. [9] revealed that complete healing was obtained in 79%, and the remaining (12.5%) showed degrees of healing, but only 8.5% showed nonhealing after a long period of management, which was in agreement with our results. The use of ozone therapy leads to a marked reduction in the associated drugs such as antibiotics, analgesics, and antifungal drugs. Zhang et al. [21] found that the efficacy rate of wound healing was significantly higher in the ozone group versus controls at the end of treatment. However, at day 20, wound size reduction of the ozone group was found to be significantly greater than that of controls, which was in agreement with our results [21]. Kushmakov et al. [22] reported that application of local ozone therapy can clean the wound rapidly, which reduces the chance of infection and period of treatment; this coincides with our results. Izadi et al. [23] reported that the use of local ozone therapy leads to inhibition of Penicillium mycelial growth on citrus caused by the oxidizing effect of ozone. The extremely high effectiveness of ozone in the treatment of diabetic foot ulcers is associated with not only its antimicrobial effect but its ability to reduce hyperglycemia, which agrees with our results [23]. Fitzpatrick et al. [24] concluded that there was no conclusive evidence of ozone therapy as a superior treatment for chronic wounds compared with standard treatments, which contradicts our results. However, the results consistently favor the application of ozone as a treatment for chronic wounds, suggesting potential for mainstream clinical practice, and this runs in line with our results [24].


  Conclusion Top


The use of local ozone therapy markedly improves the healing of diabetic foot ulcers with low incidence of recurrence.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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