Efficacy of oxygen therapy for diabetic foot ulcers: a network meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

NING Peng , ZHANG Jiaxing , CAO Hongyi ,  YANG Jing

Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Geriatric Diseases Institute of Chengdu, Chengdu 611137, P. R. China;

Corresponding?author：

YANG Jing, Email: 510163393@qq.com

Keywords：

Diabetic foot ulcers; Hyperbaric oxygen; Topical oxygen; Ozone; Efficacy; Network meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.202404036

Video：

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Objective To systematically review the efficacy of oxygen therapy for diabetic foot ulcers (DFUs). Methods The PubMed, Embase, Cochrane Library, CNKI, WanFang Data, and VIP databases were electronically searched to collect randomized controlled trials (RCT) on the efficacy of different oxygen therapies for DFUs from inception to April 1, 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Statistical analysis was performed using R software, and GraphPad Prism was used for graphical representations. Results A total of 61 RCTs involving 4 306 DFUs cases were included in the analysis. The oxygen therapies examined primarily included hyperbaric oxygen, topical oxygen, and ozone therapy. The surface under the cumulative ranking curve (SUCRA) indicated that hyperbaric oxygen therapy ranked highest for healing rate, area reduction rate, and healing time (SUCRA values were 0.957, 0.868, and 0.869, respectively). However, hyperbaric oxygen therapy also ranked higher for amputation rate and adverse events (SUCRA values were 0.616 and 0.718, respectively). Further subgroup analysis revealed that hyperbaric oxygen therapy maintained the highest ranking in area reduction rate across subgroups defined by publication language and treatment duration. Conclusion Hyperbaric oxygen therapy has advantages in terms of healing rate, area reduction rate, and healing time for DFUs, but it is also associated with higher amputation rates and adverse events. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.

Citation： NING Peng, ZHANG Jiaxing, CAO Hongyi, YANG Jing. Efficacy of oxygen therapy for diabetic foot ulcers: a network meta-analysis. Chinese Journal of Evidence-Based Medicine, 2025, 25(3): 294-302. doi: 10.7507/1672-2531.202404036 Copy

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1. McDermott K, Fang M, Boulton AJM, et al. Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers. Diabetes Care, 2023, 46(1): 209-221.
2. Primadhi RA, Septrina R, Hapsari P, et al. Amputation in diabetic foot ulcer: a treatment dilemma. World J Orthop, 2023, 14(5): 312-318.
3. Chen L, Sun S, Gao Y, et al. Global mortality of diabetic foot ulcer: a systematic review and meta-analysis of observational studies. Diabetes Obes Metab, 2023, 25(1): 36-45.
4. Armstrong DG, Tan TW, Boulton AJM, et al. Diabetic foot ulcers: a review. JAMA, 2023, 330(1): 62-75.
5. Wenhui L, Changgeng F, Lei X, et al. Hyperbaric oxygen therapy for chronic diabetic foot ulcers: an overview of systematic reviews. Diabetes Res Clin Pract, 2021, 176: 108862.
6. Yellin JI, Gaebler JA, Zhou FF, et al. Reduced hospitalizations and amputations in patients with diabetic foot ulcers treated with cyclical pressurized topical wound oxygen therapy: real-world outcomes. Adv Wound Care (New Rochelle), 2022, 11(12): 657-665.
7. Astasio-Picado á, Babiano Aá, López-Sánchez M, et al. Use of ozone therapy in diabetic foot ulcers. J Pers Med, 2023, 13(10): 1439.
8. Kwee E, Borgdorff M, Schepers T, et al. Adjunctive hyperbaric oxygen therapy in the management of severe lower limb soft tissue injuries: a systematic review. Eur J Trauma Emerg Surg, 2024, 50(3): 1093-1100.
9. Frykberg R, Andersen C, Chadwick P, et al. Use of topical oxygen therapy in wound healing. J Wound Care, 2023, 32(Sup8b): S1-S32.
10. Kushmakov R, Gandhi J, Seyam O, et al. Ozone therapy for diabetic foot. Med Gas Res, 2018, 8(3): 111-115.
11. Chen P, Vilorio NC, Dhatariya K, et al. Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update). Diabetes Metab Res Rev, 2024, 40(3): e3644.
12. ElSayed NA, Aleppo G, Aroda VR, et al. 2. Classification and diagnosis of diabetes: standards of care in diabetes-2023. Diabetes Care, 2023, 46(Suppl 1): S19-S40.
13. van Netten JJ, Bus SA, Apelqvist J, et al. Definitions and criteria for diabetes-related foot disease (IWGDF 2023 update). Diabetes Metab Res Rev, 2024, 40(3): e3654.
14. Shim SR, Kim SJ, Lee J, et al. Network meta-analysis: application and practice using R software. Epidemiol Health, 2019, 41: e2019013.
15. Mbuagbaw L, Rochwerg B, Jaeschke R, et al. Approaches to interpreting and choosing the best treatments in network meta-analyses. Syst Rev, 2017, 6(1): 79.
16. Higgins JPT, Thomas J, Chandler J, et al. Cochrane handbook for systematic reviews of interventions version 6.4 (updated August 2023). Cochrane, 2023.
17. Doctor N, Pandya S, Supe A. Hyperbaric oxygen therapy in diabetic foot. J Postgrad Med, 1992, 38(3): 112-114.
18. Faglia E, Favales F, Aldeghi A, et al. Adjunctive systemic hyperbaric oxygen therapy in treatment of severe prevalently ischemic diabetic foot ulcer: a randomized study. Diabetes Care, 1996, 19(12): 1338-1343.
19. Abidia A, Laden G, Kuhan G, et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial. Eur J Vasc Endovasc Surg, 2003, 25(6): 513-518.
20. Kessler L, Bilbault P, Ortéga F, et al. Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. Diabetes Care, 2003, 26(8): 2378-2382.
21. Duzgun AP, Satir HZ, Ozozan O, et al. Effect of hyperbaric oxygen therapy on healing of diabetic foot ulcers. J Foot Ankle Surg, 2008, 47(6): 515-519.
22. L?ndahl M, Katzman P, Nilsson A, et al. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care, 2010, 33(5): 998-1003.
23. Ma L, Li P, Shi Z, et al. A prospective, randomized, controlled study of hyperbaric oxygen therapy: effects on healing and oxidative stress of ulcer tissue in patients with a diabetic foot ulcer. Ostomy Wound Manage, 2013, 59(3): 18-24.
24. Fedorko L, Bowen JM, Jones W, et al. Hyperbaric oxygen therapy does not reduce indications for amputation in patients with diabetes with nonhealing ulcers of the lower limb: a prospective, double-blind, randomized controlled clinical trial. Diabetes Care, 2016, 39(3): 392-399.
25. Chen CY, Wu RW, Hsu MC, et al. Adjunctive hyperbaric oxygen therapy for healing of chronic diabetic foot ulcers: a randomized controlled trial. J Wound Ostomy Continence Nurs, 2017, 44(6): 536-545.
26. Santema KTB, Stoekenbroek RM, Koelemay MJW, et al. Hyperbaric oxygen therapy in the treatment of ischemic lower- extremity ulcers in patients with diabetes: results of the DAMO2CLES multicenter randomized clinical trial. Diabetes Care, 2018, 41(1): 112-119.
27. Perren S, Gatt A, Papanas N, et al. Hyperbaric oxygen therapy in ischaemic foot ulcers in type 2 diabetes: a clinical trial. Open Cardiovasc Med J, 2018, 12: 80-85.
28. Dhamodharan U, Karan A, Sireesh D, et al. Tissue-specific role of Nrf2 in the treatment of diabetic foot ulcers during hyperbaric oxygen therapy. Free Radic Biol Med, 2019, 138: 53-62.
29. Salama SE, Eldeeb AE, Elbarbary AH, et al. Adjuvant hyperbaric oxygen therapy enhances healing of nonischemic diabetic foot ulcers compared with standard wound care alone. Int J Low Extrem Wounds, 2019, 18(1): 75-80.
30. Kumar A, Shukla U, Prabhakar T, et al. Hyperbaric oxygen therapy as an adjuvant to standard therapy in the treatment of diabetic foot ulcers. J Anaesthesiol Clin Pharmacol, 2020, 36(2): 213-218.
31. Wadee AN, Fahmy SM, El-Deen HAB. Low-level laser therapy (photobiomodulation) versus hyperbaric oxygen therapy on healing of chronic diabetic foot ulcers: a controlled randomized trial. Phys Ther Rev, 2021, 26: 73-80.
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Chinese Journal of Evidence-Based Medicine

Efficacy of oxygen therapy for diabetic foot ulcers: a network meta-analysis

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