Evidence for direct CO₂ -mediated alterations in cerebral oxidative metabolism in humans

How the cerebral metabolic rates of oxygen and glucose utilization (CMRO₂ and CMR_Glc, respectively) are affected by alterations in arterial PCO₂ (PaCO₂) is equivocal and therefore was the primary question of this study.

This retrospective analysis involved pooled data from four separate studies, involving 41 healthy adults (35 males/6 females). Participants completed stepwise steady-state alterations in PaCO₂ ranging between 30 and 60 mmHg. The CMRO₂ and CMR_Glc were assessed via the Fick approach (CBF × arterial-internal jugular venous difference of oxygen or glucose content, respectively) utilizing duplex ultrasound of the internal carotid artery and vertebral artery to calculate cerebral blood flow (CBF).

The CMRO₂ was altered by 0.5 mL × min^-1 (95% CI: -0.6 to -0.3) per mmHg change in PaCO₂ (p < 0.001) which corresponded to a 9.8% (95% CI: -13.2 to -6.5) change in CMRO₂ with a 9 mmHg change in PaCO₂ (inclusive of hypo- and hypercapnia). The CMR_Glc was reduced by 7.7% (95% CI: -15.4 to -0.08, p = 0.045; i.e., reduction in net glucose uptake) and the oxidative glucose index (ratio of oxygen to glucose uptake) was reduced by 5.6% (95% CI: -11.2 to 0.06, p = 0.049) with a + 9 mmHg increase in PaCO₂.

Collectively, the CMRO₂ is altered by approximately 1% per mmHg change in PaCO₂. Further, glucose is incompletely oxidized during hypercapnia, indicating reductions in CMRO₂ are either met by compensatory increases in nonoxidative glucose metabolism or explained by a reduction in total energy production.