Topical Wound Oxygen Therapy in the Treatment of Chronic Diabetic Foot Ulcers

Robert G Frykberg, Robert G Frykberg

Abstract

Oxygen is a critical component of many biological processes and is essential for wound healing. Chronic wounds are typically characterized as being hypoxic in that the partial pressure of oxygen (pO2) in the center of the wound is often below a critical threshold necessary to fully support those enzymatic processes necessary for tissue repair. Providing supplemental oxygen can effectively raise pO2 levels to better optimize functioning of these essential enzymes. While hyperbaric oxygen therapy has been well studied in this regard, comparative clinical studies have fallen short of providing clear evidence in support of this modality for healing chronic diabetic foot ulcers (DFU). Topical oxygen therapy (TOT) has been in clinical use for over 50 years with encouraging pre-clinical and clinical studies that have shown improved healing rates when compared to standard care. Nonetheless, TOT has heretofore been discounted as an unproven wound healing modality without theoretical or clinical evidence to support its use. This review shall provide a brief summary of the role of oxygen in wound healing and, specifically, discuss the different types of topical oxygen devices and associated studies that have convincingly shown their efficacy in healing chronic DFUs. The time has come for topical oxygen therapy to be embraced as a proven adjunctive modality in this regard.

Keywords: diabetic foot ulcers; oxygen; topical oxygen therapy; wound healing.

Conflict of interest statement

R.G.F. has received prior research funding and is a Consultant for AOTI, Ltd. (Galway, Ireland).

Figures

Figure 1
Figure 1
Types of topical oxygen devices.

References

    1. Fischer B.H. Topical hyperbaric oxygen treatment of pressure sores and skin ulcers. Lancet. 1969;2:405–409. doi: 10.1016/S0140-6736(69)90113-5.
    1. Leslie C.A., Sapico F.L., Ginunas V.J., Adkins R.H. Randomized controlled trial of topical hyperbaric oxygen for treatment of diabetic foot ulcers. Diabetes Care. 1988;11:111–115. doi: 10.2337/diacare.11.2.111.
    1. Gottrup F., Dissemond J., Baines C., Frykberg R., Jensen P.O., Kot J., Kroger K., Longobardi P. Use of Oxygen Therapies in Wound Healing. J. Wound Care. 2017;26:S1–S43. doi: 10.12968/jowc.2017.26.Sup5.S1.
    1. Londahl M., Katzman P., Nilsson A., Hammarlund C. Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care. 2010;33:998–1003. doi: 10.2337/dc09-1754.
    1. Margolis D.J., Gupta J., Hoffstad O., Papdopoulos M., Glick H.A., Thom S.R., Mitra N. Lack of effectiveness of hyperbaric oxygen therapy for the treatment of diabetic foot ulcer and the prevention of amputation: A cohort study. Diabetes Care. 2013;36:1961–1966. doi: 10.2337/dc12-2160.
    1. Santema K.T.B., Stoekenbroek R.M., Koelemay M.J.W., Reekers J.A., van Dortmont L.M.C., Oomen A., Smeets L., Wever J.J., Legemate D.A., Ubbink D.T., 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;41:112–119. doi: 10.2337/dc17-0654.
    1. de Smet G.H.J., Kroese L.F., Menon A.G., Jeekel J., van Pelt A.W.J., Kleinrensink G.J., Lange J.F. Oxygen therapies and their effects on wound healing. Wound Repair Regen. 2017;25:591–608. doi: 10.1111/wrr.12561.
    1. Oropallo A.R., Serena T.E., Armstrong D.G., Niederauer M.Q. Molecular Biomarkers of Oxygen therapy in Patients with Diabetic Foot Ulcers. Biomolecules. 2021;11:925. doi: 10.3390/biom11070925.
    1. Dunnill C., Patton T., Brennan J., Barrett J., Dryden M., Cooke J., Leaper D., Georgopoulos N.T. Reactive oxygen species (ROS) and wound healing: The functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process. Int. Wound J. 2017;14:89–96. doi: 10.1111/iwj.12557.
    1. Sen C.K. Wound healing essentials: Let there be oxygen. Wound Repair Regen. 2009;17:1–18. doi: 10.1111/j.1524-475X.2008.00436.x.
    1. Gordillo G.M., Sen C.K. Evidence-based recommendations for the use of topical oxygen therapy in the treatment of lower extremity wounds. Int. J. Low Extrem. Wounds. 2009;8:105–111. doi: 10.1177/1534734609335149.
    1. Wattel F., Mathieu D. Oxygen and wound healing. Bull Acad. Natl. Med. 2005;189:853–864; discussion 864–855.
    1. Dissemond J., Kroger K., Storck M., Risse A., Engels P. Topical oxygen wound therapies for chronic wounds: A review. J Wound Care. 2015;24:53–63. doi: 10.12968/jowc.2015.24.2.53.
    1. Niederauer M.Q. How can we deliver oxygen to wounds? J. Wound Care. 2021;30:S3–S4. doi: 10.12968/jowc.2021.30.Sup5.S3.
    1. Serena T.E., Bullock M.N., Cole W., Lantis J., Li L., Moore S., Patel K., Sabo M., Wahab N., Price P. Topical oxygen therapy in the treatment of diabetic foot ulcers: A multicentre, open, randomised controlled clinical trial. J. Wound Care. 2021;30:S1–S8. doi: 10.12968/jowc.2021.30.Sup5.S7.
    1. Driver V.R., Reyzelman A., Kawalec J., French M. A Prospective, Randomized, Blinded, Controlled Trial Comparing Transdermal Continuous Oxygen Delivery to Moist Wound Therapy for the Treatment of Diabetic Foot Ulcers. Ostomy Wound Manag. 2017;63:12–28.
    1. Driver V.R., Yao M., Kantarci A., Gu G., Park N., Hasturk H. A prospective, randomized clinical study evaluating the effect of transdermal continuous oxygen therapy on biological processes and foot ulcer healing in persons with diabetes mellitus. Ostomy Wound Manag. 2013;59:19–26.
    1. Niederauer M.Q., Michalek J.E., Liu Q., Papas K.K., Lavery L.A., Armstrong D.G. Continuous diffusion of oxygen improves diabetic foot ulcer healing when compared with a placebo control: A randomised, double-blind, multicentre study. J Wound Care. 2018;27:S30–S45. doi: 10.12968/jowc.2018.27.Sup9.S30.
    1. Gordillo G.M., Roy S., Khanna S., Schlanger R., Khandelwal S., Phillips G., Sen C.K. Topical oxygen therapy induces vascular endothelial growth factor expression and improves closure of clinically presented chronic wounds. Clin. Exp. Pharmacol. Physiol. 2008;35:957–964. doi: 10.1111/j.1440-1681.2008.04934.x.
    1. Fries R.B., Wallace W.A., Roy S., Kuppusamy P., Bergdall V., Gordillo G.M., Melvin W.S., Sen C.K. Dermal excisional wound healing in pigs following treatment with topically applied pure oxygen. Mutat. Res. 2005;579:172–181. doi: 10.1016/j.mrfmmm.2005.02.023.
    1. Kalliainen L.K., Gordillo G.M., Schlanger R., Sen C.K. Topical oxygen as an adjunct to wound healing: A clinical case series. Pathophysiology. 2003;9:81–87. doi: 10.1016/S0928-4680(02)00079-2.
    1. Copeland K., Purvis A.R. A Retrospective Chart Review of Chronic Wound Patients Treated with Topical Oxygen Therapy. Adv. Wound Care (New Rochelle) 2017;6:143–152. doi: 10.1089/wound.2017.0729.
    1. Ladizinsky D., Roe D. New Insights Into Oxygen Therapy for Wound Healing. Wounds. 2010;22:294–300.
    1. Tawfick W., Sultan S. Does topical wound oxygen (TWO2) offer an improved outcome over conventional compression dressings (CCD) in the management of refractory venous ulcers (RVU)? A parallel observational comparative study. Eur. J. Vasc. Endovasc. Surg. 2009;38:125–132. doi: 10.1016/j.ejvs.2009.03.027.
    1. Tawfick W.A., Sultan S. Technical and clinical outcome of topical wound oxygen in comparison to conventional compression dressings in the management of refractory nonhealing venous ulcers. Vasc. Endovasc. Surg. 2013;47:30–37. doi: 10.1177/1538574412467684.
    1. Blackman E., Moore C., Hyatt J., Railton R., Frye C. Topical wound oxygen therapy in the treatment of severe diabetic foot ulcers: A prospective controlled study. Ostomy Wound Manag. 2010;56:24–31.
    1. Frykberg R.G., Franks P.J., Edmonds M., Brantley J.N., Teot L., Wild T., Garoufalis M.G., Lee A.M., Thompson J.A., Reach G., et al. A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen (TWO2) Therapy in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study. Diabetes Care. 2020;43:616–624. doi: 10.2337/dc19-0476.
    1. Gordillo G.M., Schlanger R., Wallace W.A., Bergdall V., Bartlett R., Sen C.K. Protocols for topical and systemic oxygen treatments in wound healing. Methods Enzymol. 2004;381:575–585. doi: 10.1016/S0076-6879(04)81037-1.
    1. Gordillo G.M., Hunt T.K., Sen C.K. Significance of oxygen therapeutics. Wound Repair Regen. 2003;11:393. doi: 10.1046/j.1524-475X.2003.11513.x.
    1. Gordillo G.M., Sen C.K. Revisiting the essential role of oxygen in wound healing. Am. J. Surg. 2003;186:259–263. doi: 10.1016/S0002-9610(03)00211-3.
    1. Lavery L.A., Killeen A.L., Farrar D., Akgul Y., Crisologo P.A., Malone M., Davis K.E. The effect of continuous diffusion of oxygen treatment on cytokines, perfusion, bacterial load, and healing in patients with diabetic foot ulcers. Int. Wound J. 2020;17:1986–1995. doi: 10.1111/iwj.13490.
    1. Yellin J.I., Gaebler J.A., Zhou F.F., Niecko T., Novins O., Ockert A., Krzynowek D., Garoufalis M.G., Lee A.M., Frykberg R.G. Reduced Hospitalizations and Amputations in Patients with Diabetic Foot Ulcers Treated with Cyclical Pressurized Topical Wound Oxygen Therapy: Real World Outcomes. 2021. submit.
    1. Nataraj M., Maiya A.G., Karkada G., Hande M., Rodrigues G.S., Shenoy R., Prasad S.S. Application of Topical Oxygen Therapy in Healing Dynamics of Diabetic Foot Ulcers—A Systematic Review. Rev. Diabet. Stud. 2019;15:74–82. doi: 10.1900/RDS.2019.15.74.
    1. Thanigaimani S., Singh T., Golledge J. Topical oxygen therapy for diabetes-related foot ulcers: A systematic review and meta-analysis. Diabet. Med. 2021:e14585. doi: 10.1111/dme.14585.

Source: PubMed

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