Perioperative hyperbaric oxygen therapy: mechanisms, evidence, and clinical application

Hyperbaric oxygen therapy delivers 100% oxygen at supra-atmospheric pressures, elevating plasma oxygen content and tissue oxygenation above normoxic levels. Once limited to decompression illness, hyperbaric oxygen therapy is gaining recognition as a perioperative adjunct with potential to mitigate complications through supra-physiologic tissue oxygenation. This review summarizes current evidence on the biological mechanisms, clinical applications, and considerations of perioperative hyperbaric oxygen therapy. Mechanistically, hyperbaric oxygen therapy has been shown to promote angiogenesis through redox-sensitive upregulation of hypoxia-inducible factor-1α and vascular endothelial growth factor, accelerate fibroblast proliferation and collagen synthesis, mobilize CD34-positive progenitor cells, and mitigate ischemia-reperfusion injury via antioxidant and anti-inflammatory pathways. Clinically, hyperbaric oxygen therapy has demonstrated improved graft uptake, flap salvage, and muscle recovery across trauma, reconstructive, and orthopedic contexts, and has shown promise in cardiac surgery preconditioning. The safety of hyperbaric oxygen therapy is favorable, with serious complications occurring in fewer than 0.5% of treatments. Despite accumulating evidence of its biological effect, widespread perioperative adoption remains constrained by cost, coverage limitations, and protocol heterogeneity. Higher-quality studies, including standardized dosing parameters and multicenter randomized trials, are needed to define optimal timing and patient selection. As health systems move toward precision perioperative optimization, hyperbaric oxygen appears to be gaining ground as a compelling, evidence-supported tool to improve surgical outcomes while aligning with the broader goals of restorative and regenerative medicine.