Exposure to Non-Steady-State Oxygen Is Reflected in Changes to Arterial Blood Gas Values, Prefrontal Cortical Activity, and Systemic Cytokine Levels.

Onboard oxygen-generating systems (OBOGSs) provide increased inspired oxygen (FiO2) to mitigate the risk of neurologic injury in high altitude aviators. OBOGSs can deliver highly variable oxygen concentrations oscillating around a predetermined FiO2 set point, even when the aircraft cabin altitude is relatively stable. Steady-state exposure to 100% FiO2 evokes neurovascular vasoconstriction, diminished cerebral perfusion, and altered electroencephalographic activity. Whether non-steady-state FiO2 exposure leads to similar outcomes is unknown. This study characterized the physiologic responses to steady-state and non-steady-state FiO2 during normobaric and hypobaric environmental pressures emulating cockpit pressures within tactical aircraft. The participants received an indwelling radial arterial catheter while exposed to steady-state or non-steady-state FiO2 levels oscillating ± 15% of prescribed set points in a hypobaric chamber. Steady-state exposure to 21% FiO2 during normobaria produced arterial blood gas values within the anticipated ranges. Exposure to non-steady-state FiO2 led to PaO2 levels higher upon cessation of non-steady-state FiO2 than when measured during steady-state exposure. This pattern was consistent across all FiO2 ranges, at each barometric condition. Prefrontal cortical activation during cognitive testing was lower following exposure to non-steady-state FiO2 >50% and <100% during both normobaria and hypobaria of 494 mmHg. The serum analyte levels (IL-6, IP-10, MCP-1, MDC, IL-15, and VEGF-D) increased 48 h following the exposures. We found non-steady-state FiO2 levels >50% reduced prefrontal cortical brain activation during the cognitive challenge, consistent with an evoked pattern of neurovascular constriction and dilation.

Characterizing the Dose Response of Hyperoxia with Brain Perfusion.

BACKGROUND: Tactical aviators require administration of enhanced inspired oxygen concentrations (hyperoxia) to reduce risk of hypobaric hypoxia and decompression injuries. Hyperoxia is not without consequence; it reduces cerebral perfusion (CBF). Characterizing the relationship between FIO2 and CBF is necessary to establish FIO2 levels that do not reduce CBF yet are sufficient to mitigate risk of in-flight physiological stressors. To achieve that goal, this study's objective was to determine whether a dose-response relationship exists between FIO2 and CBF and, if so, the FIO2 at which CBF significantly declines.METHODS: Healthy male and female subjects (N = 26) were randomized to receive either low dose FIO2 of 30%, 40%, 50%, and 100% (Arm 1) or high dose FIO2 of 60%, 70%, 80%, and 100% (Arm 2), followed by a return to 21% for both groups. Subjects were placed within a 3-Tesla MRI scanner equipped with pseudocontinuous arterial spin labeling software (pCASL) to measure CBF. Baseline CBF measurements were obtained during exposure to 21% FIO2, with subsequent CBF measurements obtained at each predetermined FIO2 level.RESULTS: Baseline CBF did not differ between subjects in Arm 1 and Arm 2. Low dose FIO2 ≤ 50% did not affect CBF. In contrast, high dose FIO2 ≥ 60% significantly reduced CBF. Exposure to 100% FIO2 led to similar reductions of CBF for subjects in both Arm 1 and Arm 2.DISCUSSION: The neurovascular system appears to respond to increasing FIO2 levels in a dose dependent manner, with significant reductions in CBF with FIO2 exposures ≥ 60%.Damato EG, Fillioe SJ, Vannix IS, Norton LK, Margevicius SP, Beebe JL, Decker MJ. Characterizing the dose response of hyperoxia with brain perfusion. Aerosp Med Hum Perform. 2022; 93(6):493-498.