Influence of end‐tidal CO₂ on cerebral blood flow during orthostatic stress in controls and adults with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract Brain perfusion is sensitive to changes in CO 2 levels (CO 2 reactivity). Previously, we showed a pathological cerebral blood flow (CBF) reduction in the majority of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients during orthostatic stress. Limited data are available on the relation between CO 2 and CBF changes in ME/CFS patients. Therefore, we studied this relation between ME/CFS patients and healthy controls (HC) during tilt testing. In this retrospective study, supine and end‐tilt CBF, as measured by extracranial Doppler flow, were compared with P ET CO 2 data in female patients either with a normal heart rate and blood pressure (HR/BP) response or with postural orthostatic tachycardia syndrome (POTS), and in HC. Five hundred thirty‐five female ME/CFS patients and 34 HC were included. Both in supine position and at end‐tilt, there was a significant relation between CBF and P ET CO 2 in patients ( p < 0.0001), without differences between patients with a normal HR/BP response and with POTS. The relations between the %CBF change and the P ET CO 2 reduction were both significant in patients and HC ( p < 0.0001 and p = 0.0012, respectively). In a multiple regression analysis, the patient/HC status and P ET CO 2 predicted CBF. The contribution of the P ET CO 2 to CBF changes was limited, with low adjusted R 2 values. In female ME/CFS patients, CO2 reactivity, as measured during orthostatic stress testing, is similar to that of HC and is independent of the type of hemodynamic abnormality. However, the influence of CO 2 changes on CBF changes is modest in female ME/CFS patients.