Frostbite
Hyperbaric Oxygen Therapy for Frostbite
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 is a potential adjunctive treatment for frostbite, which is associated with tissue ischaemia, necrosis and, upon rewarming, reperfusion injury (RPI). HBOT can enhance oxygen delivery, improve microcirculation, reduce inflammation, promote angiogenesis, and inhibit reperfusion injury. Clinical evidence indicates that adjunctive HBO can improve outcomes for frostbite patients, particularly by reducing tissue loss and the need for amputation.
Mechanisms of Action of HBOT
HBOT may aid in frostbite treatment through multiple physiological mechanisms, primarily by enhancing oxygen delivery to ischaemic tissues and promoting healing.
1. Enhanced Oxygen Delivery: In frostbite, cold-induced vasoconstriction and subsequent ischaemia lead to tissue hypoxia. HBOT significantly increases the oxygen content in blood plasma, thereby facilitating oxygen delivery to hypoxic tissues, thus reducing ischaemia and tissue necrosis (Cannellotto et al., 2024).
2. Reduction of RPI: Upon rewarming, RPI can cause additional damage through oxidative stress and inflammation. HBOT mitigates RPI by decreasing inflammation and the production of reactive oxygen species (Francis et al., 2017).
3. Angiogenesis: HBOT stimulates angiogenesis via the release of vascular VEGF and other angiogenic factors, thereby enhancing blood flow to the damaged tissues and supporting tissue regeneration (De Wolde et al., 2021).
4. Anti-Inflammatory Effects: Inflammation is a critical component of frostbite pathophysiology. HBOT exerts anti-inflammatory effects by reducing the levels of pro-inflammatory cytokines such as TNF-α, while promoting the release of anti-inflammatory cytokines (De Wolde et al., 2021).
5. Enhanced Leukocyte Function: HBOT enhances the bactericidal function of leukocytes (De Wolde et al., 2022), which is particularly important in frostbite where secondary infections are common.
6. Reduction of Oedema: HBOT reduces capillary permeability and facilitates lymphatic drainage, decreasing tissue oedema and pressure (Nylander et al., 1985).
Benefits of HBOT for Patients with Frostbite
HBOT is generally well tolerated and serious side effects are rare (Camporesi, 2014). Patients with frostbite may experience several benefits from HBOT that contribute to improved outcomes and fewer complications.
1. Reduced Tissue Loss: One of the most significant benefits of HBOT is the reduction in tissue loss. By enhancing oxygenation and promoting tissue repair, HBOT may help salvage tissue that would otherwise be necrotic, decreasing the need for surgical debridement or amputation.
2. Faster Healing: HBOT may accelerate the healing process (Bhutani & Vishwanath, 2012) of frostbite injuries by improving oxygen delivery, reducing inflammation and enhancing angiogenesis.
3. Pain Relief: Frostbite is associated with significant pain, both during the initial injury and throughout the healing process. HBOT can help alleviate pain by reducing inflammation and promoting tissue repair.
4. Improved Functional Outcomes: By reducing tissue loss, preserving the function of affected extremities and accelerating healing, HBOT may improve functional outcomes for frostbite patients.
5. Prevention of Complications: Secondary infections and chronic wounds are common complications of frostbite. HBOT’s antimicrobial effects and role in promoting wound healing may help prevent these complications.
Clinical Evidence Supporting HBOT of Frostbite
HBOT may be a therapeutic option either as a solo treatment or in combination with vasodilatory, anticoagulatory or haemorrheological agents for the treatment of frostbite (Robins et al., 2023). Although more large-scale randomised controlled trials are needed, several studies and case reports support the use of HBOT in treating frostbite.
1. Reviews: A review of 16 cases in the literature by Folio et al. (2007) concluded that HBOT may be a useful adjunctive therapy for frostbite, even when treatment is delayed by several weeks. A retrospective review of 22 cases concluded that HBOT may have a positive impact on the demarcation level of frostbite (Ghumman et al., 2019).
2. Comparative Studies: HBOT (100% O2, 2.5 ATA, 150 mins, 14 daily sessions) with iloprost improves digit salvage in severe frostbite compared to iloprost alone (Magnan et al., 2021).
3. Case Reports: Numerous case studies and clinical reports have documented the effectiveness of HBOT in treating frostbite, even after delays of several weeks. For example, an 11-year-old boy with severe frostbite of his fingers was treated 3 days after injury with HBOT (100% O2, 2.4 ATA, 90 mins, 14 daily sessions), and the planned amputations were avoided (Von Heimburg et al., 2001). In another case, after a 12-day delay, a 28-year-old man avoided toe amputations following HBOT at 2.5 ATA for 90 min (28 daily sessions), which was associated with an increase in tissue capillaries (Finderle & Cankar, 2002). A 28-year-old female climber suffered frostbite to her fingers and, after a two-week delay, HBOT (21 sessions over 3 months) was initiated. No fingers required amputation and the patient maintained normal neurological motor function and only mildly decreased sensation (Folio et al., 2007). In a case in which the patient was treated without delay, a 17-year-old-male was treated with HBOT (100% O2, 2.4 ATA, 90 mins, twice daily for 13 sessions) within hours of rewarming and had no tissue loss or functional impairment (Robins, 2019).
Conclusion
HBOT offers a promising adjunctive treatment for frostbite by enhancing oxygen delivery, reducing RPI, exerting anti-inflammatory effects, promoting angiogenesis and improving leukocyte function. Clinical evidence indicates that HBOT improves functional outcomes and prevents complications, which may benefit frostbite patients.
References
Bhutani, S., & Vishwanath, G. (2012). Hyperbaric oxygen and wound healing. Indian Journal of Plastic Surgery, 45(02), 316-324.
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.
De Wolde, S. D., Hulskes, R. H., Weenink, R. P., Hollmann, M. W., & Van Hulst, R. A. (2021). The effects of hyperbaric oxygenation on oxidative stress, inflammation and angiogenesis. Biomolecules, 11(8), 1210.
De Wolde, S. D., Hulskes, R. H., de Jonge, S. W., Hollmann, M. W., van Hulst, R. A., Weenink, R. P., & Kox, M. (2022). The effect of hyperbaric oxygen therapy on markers of oxidative stress and the immune response in healthy volunteers. Frontiers in Physiology, 13, 826163.
Folio, L. R., Arkin, K., & Butler, W. P. (2007). Frostbite in a mountain climber treated with hyperbaric oxygen: case report. Military Medicine, 172(5), 560-563.
Finderle, Z., & Cankar, K. (2002). Delayed treatment of frostbite injury with hyperbaric oxygen therapy: a case report. Aviation, Space, and Environmental Medicine, 73(4), 392-394.
Francis, A., & Baynosa, R. (2017). Ischaemia-reperfusion injury and hyperbaric oxygen pathways: a review of cellular mechanisms. Diving and Hyperbaric Medicine, 47(2), 110.
Ghumman, A., Ashton, R., Wherrett, C., & Malic, C. (2019). Treatment of frostbite with hyperbaric oxygen therapy: A single center’s experience of 22 cases. Wounds, 31(12), 322-325.
Magnan, M. A., Gayet-Ageron, A., Louge, P., Champly, F., Joffre, T., Lovis, C., & Pignel, R. (2021). Hyperbaric oxygen therapy with iloprost improves digit salvage in severe frostbite compared to iloprost alone. Medicina, 57(11), 1284.
Nylander, G., Lewis, D., Nordström, H., & Larsson, J. (1985). Reduction of postischemic edema with hyperbaric oxygen. Plastic and Reconstructive Surgery, 76(4), 596-601.
Robins M. (2019). Early treatment of frostbite with hyperbaric oxygen and pentoxifylline: A case report. Undersea & Hyperbaric Medicine, 46(4), 521–526.
Robins, M., Hendriksen, S., & Cooper, J. S. (2023). Hyperbaric Management of Frostbite. In: StatPearls. StatPearls Publishing, Treasure Island (FL).
Von Heimburg, D., Noah, E. M., Sieckmann, U. P., & Pallua, N. (2001). Hyperbaric oxygen treatment in deep frostbite of both hands in a boy. Burns, 27(4), 404-408.