Hyperbaric oxygen (HBO₂) therapy serves as a critical bridge treatment for severe anemia when red blood cell transfusion is not possible due to religious objection, crossmatch incompatibility, or blood unavailability. Hemoglobin levels below 3.6 g/dL are clearly inadequate for tissue oxygenation, and accumulative oxygen debt exceeding 33 L/m2 within four hours of severe hemorrhage is unsurvivable. HBO₂ administered at pressures of 2 to 3 ATA dissolves sufficient oxygen directly in plasma to compensate for the deficit in hemoglobin-bound oxygen-carrying capacity, while concurrent use of hematinics and erythropoietin-stimulating strategies supports endogenous red blood cell regeneration during surface intervals between treatments. Controlled animal studies spanning from 1943 through the 1990s consistently demonstrate improved survival in HBO₂-treated groups compared to normobaric air controls across multiple hemorrhagic shock models; human case reports, case series, and one controlled prospective trial in post-hepatectomy patients further support clinical efficacy. Classified as an AHA Class IIb indication with long-standing CMS approval, HBO₂ carries a cost comparable to a single unit of packed red blood cells and maintains a favorable safety profile with few and infrequent side effects. These findings position HBO₂ as a practical, low-technology, cost-competitive intervention for reducing accumulated oxygen debt in critically anemic patients across settings including emergency departments, operative units, and intensive care environments.

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