Non-Healing Wounds

Written By Elizabeth Gaffney

Hyperbaric Oxygen Therapy for Non-Healing Wounds

Introduction

Hyperbaric Oxygen Therapy (HBOT) consists of breathing oxygen at a pressure higher than local atmospheric pressure for multiple sessions for the treatment or prevention of specific diseases. As per the European Code of Good Practice (Kot et al.), there is a general consensus that the term HBOT can only be applied when the partial pressure of oxygen in breathing mixture exceeds 1.5 absolute atmosphere (ATA) for a minimum period of 60 minutes (excluding compression and decompression).

HBOT has wide-ranging benefits in the treatment of non-healing wounds, which are common in patients with diabetes or vascular diseases and those undergoing radiation therapy. In non-healing wounds, hypoxia and inflammation may delay healing, but HBOT enhances oxygen delivery to tissues, triggering a cascade of physiological responses that promote tissue repair and regeneration.

Mechanisms of Action of HBOT

Hyperbaric oxygen therapy facilitates wound healing through several mechanisms, primarily by enhancing oxygen delivery to tissues.

  1. Enhanced oxygenation: Due to inflammation and disruption of the vasculature, wounds are often hypoxic, which prevents healing. HBOT increases the amount of dissolved oxygen in plasma, significantly enhancing oxygen delivery to hypoxic wounds and enhancing healing (Cannellotto et al., 2024).

  2. Angiogenesis: Angiogenesis is impaired in chronic wounds, which leads to chronic hypoxia and impaired micronutrient delivery, causing further tissue damage. HBOT stimulates angiogenesis (Huang et al., 2020) and improves blood supply to the wound site by inducing the release of VEGF and other pro-angiogenic factors.

  3. Anti-inflammatory effects: Chronic inflammation is a hallmark of non-healing wounds. HBOT exerts anti-inflammatory effects (Capó et al., 2023) by decreasing the levels of pro-inflammatory cytokines and reducing the infiltration of inflammatory cells into the wound site.

  4. Collagen synthesis: Collagen plays a critical role in wound healing, but the wound’s microenvironment (e.g., inflammatory cells and cytokines) may affect collagen remodelling and delay wound healing. As well as reducing inflammation, HBOT promotes the proliferation and activity of fibroblasts (Huang et al., 2020), thereby accelerating collagen synthesis and wound repair (Bhutani & Verma, 2010).

  5. Antimicrobial effects: Non-healing wounds are liable to infection, which further delays healing. By increasing oxygen levels in tissues, HBOT inhibits the growth of anaerobic bacteria and enhances the ability of leukocytes to kill bacteria (Memar et al., 2019).

Benefits of HBOT for Patients with Chronic Wounds

HBOT is generally well tolerated and serious side effects are rare (Camporesi, 2014). Patients with non-healing wounds may experience a range of benefits from HBOT that improve outcomes and quality of life.

1. Accelerated wound healing: HBOT can significantly improve the closure rates of chronic wounds such as diabetic foot ulcers, pressure sores, and radiation-induced injuries, thus reducing the risk of complications and shortening hospital stays (Kranke et al., 2015).

2. Decreased risk of amputation: In severe cases of non-healing wounds, HBOT may improve wound healing and limb salvage rates, thereby decreasing the need for amputations (Sharma et al., 2021).

3. Decreased chronic pain: Non-healing wounds are often associated with chronic pain and HBOT may reduce chronic pain in many conditions (Sutherland et al., 2016) by promoting tissue repair and reducing inflammation.

4. Increased mobility: For patients with non-healing wounds affecting the lower extremities, impaired mobility is a common issue. By accelerating wound healing and reducing the risk of complications, HBOT may enhance mobility.

Clinical Evidence Supporting HBOT of Non-Healing Wounds

The clinical efficacy of HBOT in treating non-healing wounds is supported by numerous studies and clinical trials. HBOT is a recognised treatment by the US FDA as a treatment for non-healing and diabetic lower extremity wounds, as well as by Diabetes Ireland, the European Committee on Hyperbaric Medicine (ECHM) and the Undersea and Hyperbaric Medical Society (UHMS).

1. Diabetic leg ulcers: Of note, several systematic reviews and meta-analyses of randomised clinical trials describe the effectiveness of HBOT (typically 100% O2, 2.2–2.8 ATA, 90 mins, 20–60 sessions) in improving the healing of diabetic leg ulcers and/or reducing the requirement for amputation (Stoekenbroek et al., 2014; Kranke et al., 2015; Golledge & Singh, 2019; Brouwer et al., 2020).

2. Diabetic foot ulcers: Several meta-analyses of clinical trials for HBOT (typically 100% O2, 2–3 ATA, 45–120 mins, 4–50 sessions) of diabetic foot ulcers provide evidence that HBOT reduces the wound area and is effective as an adjunct treatment measure for diabetic foot ulcers (Moreira Da Cruz et al., 2022; Sharma et al., 2021; Zhao et al., 2017).

3. Venous leg ulcers: There is also evidence supporting HBOT for venous leg ulcers. A systematic review of clinical studies reporting HBOT of venous leg ulcers (typically 100% O2, 1.8–2.5 ATA, 72–90 mins, 10–30 sessions) concluded that there is a significant benefit of HBOT in terms of reducing ulcer size (Keohane et al., 2023).

4. Radionecrosis: HBOT at 2–2.5 ATA for 60–120 mins over 30–60 sessions has also been used to treat chronic wounds induced by radiation, such as radionecrosis, and may enhance tissue repair and reduce radiation-induced fibrosis (Borab et al., 2017).

5. Bedsores: HBOT at 2 ATA for 60 mins (10 sessions) may be beneficial for the treatment of decubitus ulcers (bedsores) and lead to a reduction in wound size and inflammatory markers (Fukai et al., 2005).

Conclusion

By enhancing oxygen delivery, stimulating angiogenesis, promoting fibroblast activity, reducing inflammation, and exerting antimicrobial effects, hyperbaric oxygen therapy offers a promising adjunctive treatment that may significantly improve wound healing outcomes.

References

  • Bhutani, S., & Verma, R. (2010). Hyperbaric oxygen therapy in non-healing wounds. Journal of Marine Medical Society, 12(2), 89-92.

  • Borab, Z., Mirmanesh, M. D., Gantz, M., Cusano, A., & Pu, L. L. (2017). Systematic review of hyperbaric oxygen therapy for the treatment of radiation-induced skin necrosis. Journal of Plastic, Reconstructive and Aesthetic Surgery, 70(4), 529-538.

  • Brouwer, R. J., Lalieu, R. C., Hoencamp, R., van Hulst, R. A., & Ubbink, D. T. (2020). A systematic review and meta-analysis of hyperbaric oxygen therapy for diabetic foot ulcers with arterial insufficiency. Journal of Vascular Surgery, 71(2), 682-692.

  • Camporesi, E. M. (2014). Side effects of hyperbaric oxygen therapy. Undersea & Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Medical Society, Inc, 41(3), 253-257.

  • Cannellotto, M., Yasells García, A., & Landa, M. S. (2024). Hyperoxia: Effective Mechanism of hyperbaric treatment at mild-pressure. International Journal of Molecular Sciences, 25(2), 777.

  • Capó, X., Monserrat-Mesquida, M., Quetglas-Llabrés, M., Batle, J. M., Tur, J. A., Pons, A., … & Tejada, S. (2023). Hyperbaric oxygen therapy reduces oxidative stress and inflammation, and increases growth factors favouring the healing process of diabetic wounds. International Journal of Molecular Sciences, 24(8), 7040.

  • Fukai, T., Nakata, M., & Takeda, A. (2005). Oxygen hyperbaric pressure therapy (OHPT) for decubitus ulcers. Wound Repair and Regeneration, 13(1), A15-A15.

  • Golledge, J., & Singh, T. P. (2019). Systematic review and meta‐analysis of clinical trials examining the effect of hyperbaric oxygen therapy in people with diabetes‐related lower limb ulcers. Diabetic Medicine, 36(7), 813-826.

  • Huang, X., Liang, P., Jiang, B., Zhang, P., Yu, W., Duan, M., … & Huang, X. (2020). Hyperbaric oxygen potentiates diabetic wound healing by promoting fibroblast cell proliferation and endothelial cell angiogenesis. Life Sciences, 259, 118246.

  • Keohane, C., Westby, D., Nolan, F. C., Twyford, M., Tawfick, W., & Walsh, S. R. (2023). Hyperbaric oxygen as an adjunct in the treatment of venous ulcers: A systematic review. Vascular and Endovascular Surgery, 57(6), 607-616.

  • Kranke, P., Bennett, M. H., Martyn‐St James, M., Schnabel, A., Debus, S. E., & Weibel, S. (2015). Hyperbaric oxygen therapy for chronic wounds. Cochrane Database of Systematic Reviews, (6).

  • Memar, M. Y., Yekani, M., Alizadeh, N., & Baghi, H. B. (2019). Hyperbaric oxygen therapy: Antimicrobial mechanisms and clinical application for infections. Biomedicine & Pharmacotherapy, 109, 440-447.

  • Moreira Da Cruz D.L., Oliveira-Pinto, J., & Mansilha, A. (2021). The role of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers: a systematic review with meta-analysis of randomized controlled trials on limb amputation and ulcer healing. International Angiology, 41(1), 63-73.

  • Sharma, R., Sharma, S. K., Mudgal, S. K., Jelly, P., & Thakur, K. (2021). Efficacy of hyperbaric oxygen therapy for diabetic foot ulcer, a systematic review and meta-analysis of controlled clinical trials. Scientific Reports, 11(1), 2189.

  • Stoekenbroek, R. M., Santema, T. B., Legemate, D. A., Ubbink, D. T., Van Den Brink, A., & Koelemay, M. J. W. (2014). Hyperbaric oxygen for the treatment of diabetic foot ulcers: A systematic review. European Journal of Vascular and Endovascular Surgery, 47(6), 647-655.

  • Sutherland, A. M., Clarke, H. A., Katz, J., & Katznelson, R. (2016). Hyperbaric oxygen therapy: A new treatment for chronic pain? Pain Practice, 16(5), 620-628.

  • Zhao, D., Luo, S., Xu, W., Hu, J., Lin, S., & Wang, N. (2017). Efficacy and safety of hyperbaric oxygen therapy used in patients with diabetic foot: A meta-analysis of randomized clinical trials. Clinical Therapeutics, 39(10), 2088-2094.

Elizabeth Gaffney https://www.sourceprojects.co
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