Hyperbaric Oxygen Therapy in Non-Healing Wounds: A Critical Narrative Review of Mechanisms, Clinical Applications and Outcomes

Abstract

Non-healing wounds impose a substantial and rising clinical and economic burden, and hyperbaric oxygen therapy remains one of the most contested adjuncts in their management. Half a century of mechanistic work has established that intermittent hyperoxia raises dissolved plasma oxygen far above the physiological range, generates a controlled oxidative stress, activates hypoxia-inducible factor signalling, mobilises vasculogenic progenitor cells and augments oxidative bacterial killing. Translation of that biology into reproducible clinical benefit has, however, been inconsistent. This critical narrative review examines why mechanistic plausibility and clinical performance have diverged, and defines the conditions under which the therapy can be defended. Peer-reviewed literature was identified through structured searching of biomedical databases and open scholarly indexes, supplemented by backward and forward citation tracking, publisher records and retraction notices, with bibliographic details and digital object identifiers verified individually. The synthesis is organised around mechanisms, the randomised and observational evidence in diabetes-related foot ulceration, the evidence position in late radiation tissue injury, venous leg ulceration, necrotising soft tissue infection, compromised flaps and rare refractory wounds, and the determinants of patient selection, dose, safety and cost. Randomised trials in diabetes-related foot ulceration diverge sharply, and this divergence tracks systematically with baseline perfusion, ulcer severity, comparator design and per-protocol treatment exposure rather than with chance alone. Aggregated syntheses reproduce these differences and have additionally been contaminated by several retracted meta-analyses, an underappreciated threat to the integrity of the pooled estimates now entering guidelines. The evidence is strongest for ischaemic, severe-grade ulceration in patients with measurable oxygen responsiveness and weakest for well-perfused, non-ischaemic wounds. Prospective, physiologically stratified randomised trials with adequate treatment exposure and standardised endpoints are the principal unmet requirement. Until such trials are reported, hyperbaric oxygen therapy is best regarded as a selectively indicated adjunct rather than a general treatment for wounds that fail to heal.