Hidden Overshoot in Cerebral Blood Flow: Implications for Accurate Assessment of Cerebral CO2 Reactivity.

The impact of temporal and individual differences in respiratory and cerebrovascular responses on the assessment of cerebrovascular carbon dioxide (CO2) reactivity (CVR) using the Douglas bag method remains unclear. We hypothesized that accurate CVR assessment requires attaining a respiratory steady-state during CO2 inhalation, followed by stabilization of middle cerebral artery mean blood velocity (MCA Vmean), mediated by changes in arterial CO2 tension. To test this hypothesis, we conducted three 8-minute CO2 inhalation trials (at 0%, 3.5%, and 5%) and analyzed minute-by-minute responses in 32 healthy participants. Twelve participants (37.5%) exhibited an overshoot in MCA Vmean immediately after the onset of CO2 inhalation. When averaged across all participants, CVR reached an apparent steady-state within 2-3 minutes. In contrast, in the overshoot group, MCA Vmean increased acutely and thereafter decreased toward a plateau at approximately 6-7 minutes, whereas ventilation increased progressively throughout the exposure. The magnitude of the MCA Vmean overshoot was significantly associated with central respiratory chemoreflex sensitivity (r = 0.560, P = 0.0009), but not with CVR (r = -0.206, P = 0.258). These findings indicate that inter-individual variability in CVR estimates obtained using the Douglas bag method may be attributable to inter-individual differences in cerebrovascular regulation arising from respiratory responses to CO2 inhalation. Consequently, assessing CVR during the early phase of CO2 inhalation may over- or underestimate steady-state cerebrovascular responsiveness because of inter-individual differences in respiratory or cerebrovascular control. Accordingly, we recommend a minimum CO2 inhalation duration of 6-7 minutes to ensure attainment of a steady-state when assessing CVR.