Precision hyperbaric oxygen therapy: a biomarker-driven framework

Hyperbaric oxygen therapy (HBOT) remains limited by insufficient individualization, a lack of biomarker-guided dosing, and heterogeneous clinical outcomes across indications and patient populations. We propose a translational, biomarker-driven framework for treating HBOT as a measurable and titratable intervention. This narrative review presents a conceptual framework rather than a formal systematic review or a clinically validated dosing algorithm.

Dosing is quantified using pressure-time integral (PTI) and cumulative oxygen exposure. A three-tier biomarker architecture supports decision-making: proximal sensors (redox balance, mitochondrial function, endothelial and microcirculatory responses), mechanistic mediators (inflammation-immunity and senescence), and integrative endpoints (epigenetic clocks, multi-omics, functional outcomes, and patient-reported measures). These signals are proposed for integration into a Composite Response Index (CRI) to support prospective evaluation of real-time monitoring and adaptive titration across treatment cycles and clinical scenarios. Evidence is synthesized narratively across HBOT indications, oxygen-biology mechanisms, safety literature, trial-methodology guidance, and biomarker-practicality considerations.

The framework proposes candidate, prospectively testable rules for dose adjustment, phenotype-based stratification, and biologically aligned monitoring schedules. It supports dual-channel stratification by indication and phenotype, enabling hypothesis-driven "right patient, right dose" strategies, and integrates evidence generation across randomized trials, platform studies, and real-world data using causal inference and Bayesian approaches. These operational rules are intended as framework-level proposals and require prospective validation before routine clinical implementation.

This biomarker-driven strategy operationalizes HBOT as a quantifiable intervention, enabling personalized dosing, improved reproducibility, and more consistent clinical responses, with translational potential across neurorehabilitation, cardiometabolic health, wound care, and healthy ageing. The CRI, PTI-based dose mapping, biomarker thresholds, and titration rules should therefore be interpreted as a de novo implementation framework and prospective validation target, not as clinically validated decision limits.