Rethinking PbtO₂ responses to hyperoxemia: laying the groundwork for a new approach to multimodal neuromonitoring

The interpretation of brain tissue oxygen tension (PbtO₂) in neurocritical care remains controversial, particularly during hyperoxemic conditions. In this comment on the article by Bögli et al., we propose that the observed rise in PbtO₂ following increased FiO₂ may be better explained by the conformational transition of hemoglobin from the relaxed (R) to the tense (T) state at the end of cerebral capillaries. This shift, which enhances oxygen release and buffering capacity, helps maintain arterial-like oxygen tension despite low venous oxygen saturation. We discuss the implications of this mechanism for understanding multimodal neuromonitoring (MMM) data, the effects of cerebral autoregulation, and the role of blood storage lesions. Recognizing hemoglobin conformation as a physiological determinant may help refine MMM thresholds and neuroprotective strategies in traumatic brain injury.