The Effectiveness of Ozone Therapy on Diabetic Ulcer Repair: A Systematic Review and Meta-analysis: Study of Changes in Wound Size

Abstract

Introduction: Diabetic foot ulcer (DFU) is a typical dermatological complication often found in patients with diabetes mellitus (DM). Chronic hyperglycemia state causes microvascular impairment that leads to loss of peripheral sensory, motor, and autonomous functions. The current diabetic ulcer therapy has not yet provided a satisfactory reduction of the ulcer area; thus, several adjuvant therapies were tried, such as using ozone therapy, either systematically or topically. Ozone increases the cell membrane permeability to glucose, increases oxygen metabolism, improves oxidative preconditioning, stimulates endogenous antioxidant systems, and has anti-inflammatory and antibacterial effects. Methods: This study was an analytic observational study, with systematic review and meta-analysis. Data searching were conducted online at Pubmed-MEDLINE, Scopus, EBSCOhost, ProQuest, Cochrane library, ClinicalTrials.gov, and Google Scholar, as well as hand-searching from libraries in Indonesia. Five most relevant articles included in the qualitative (systematic review) (n = 449) and three of those five articles included in the quantitative analysis (meta-analysis) (n = 211). Reduction of ulcer area was assessed. Results: The meta-analysis of effectiveness of ozone intervention group compared to the control group showed a homogeneity in data (Q=95.547, df=2; p=0.000, Tau2=5.276). Meta-analysis showed the value of Q statistic was z value = -9.478; (p=0.000). This shows that the overall administration of ozone can significantly improve the diabetic ulcer repair. The overall standardized mean difference showed an increase in the reduction of ulcer area following ozone therapy was -1.740 (95% CI [-2.100 to -1.380], p=0.00). These results indicate that the ulcer healing of the intervention group was significantly better than the control group. Conclusion: Systematic review and meta-analysis results show that the application of ozone therapy significantly improves DFU repair.