Hyperoxia results in increased aerobic metabolism following acute brain injury

Acute brain injury is associated with depressed aerobic metabolism. Below a critical mitochondrial pO(2) cytochrome c oxidase, the terminal electron acceptor in the mitochondrial respiratory chain, fails to sustain oxidative phosphorylation. After acute brain injury, this ischaemic threshold might be shifted into apparently normal levels of tissue oxygenation. We investigated the oxygen dependency of aerobic metabolism in 16 acutely brain-injured patients using a 120-min normobaric hyperoxia challenge in the acute phase (24–72 h) post-injury and multimodal neuromonitoring, including transcranial Doppler ultrasound-measured cerebral blood flow velocity, cerebral microdialysis-derived lactate-pyruvate ratio (LPR), brain tissue pO(2) (p(br)O(2)), and tissue oxygenation index and cytochrome c oxidase oxidation state (oxCCO) measured using broadband spectroscopy. Increased inspired oxygen resulted in increased p(br)O(2) [Δp(br)O(2) 30.9 mmHg p < 0.001], reduced LPR [ΔLPR −3.07 p = 0.015], and increased cytochrome c oxidase (CCO) oxidation (Δ[oxCCO] + 0.32 µM p < 0.001) which persisted on return-to-baseline (Δ[oxCCO] + 0.22 µM, p < 0.01), accompanied by a 7.5% increase in estimated cerebral metabolic rate for oxygen (p = 0.038). Our results are consistent with an improvement in cellular redox state, suggesting oxygen-limited metabolism above recognised ischaemic p(br)O(2) thresholds. Diffusion limitation or mitochondrial inhibition might explain these findings. Further investigation is warranted to establish optimal oxygenation to sustain aerobic metabolism after acute brain injury.