Cerebral blood flow and end-tidal CO 2 predict lightheadedness during head-up tilt in patients with orthostatic intolerance.

Orthostatic intolerance (OI) is a common problem. Reliable markers of OI are missing, as orthostatic blood pressure and heart rate poorly correlate with orthostatic symptoms. The objective of this study was to assess the relationship between orthostatic lightheadedness and cerebral blood flow. In this retrospective study patients with OI were evaluated at the Autonomic Laboratory of the Department of Neurology, Brigham and Women's Faulkner Hospital, Boston. The 10-minute head-up tilt test was performed as a part of autonomic testing. Orthostatic lightheadedness was evaluated at every minute of the head-up tilt. Heart rate, blood pressure, capnography, and cerebral blood flow velocity (CBFv) in the middle cerebral artery using transcranial Doppler were measured. Repeated-measures design with a linear mixed-effects model was used to evaluate the relationship between orthostatic lightheadedness and hemodynamic variables. Correlation analyses were done by calculating Pearson's coefficient. Twenty-two patients with OI were compared to nineteen controls. Orthostatic CBFv and end-tidal CO 2 decreased in OI patients compared to controls (p < 0.001) and predicted orthostatic lightheadedness. Orthostatic heart rate and blood pressure failed to predict orthostatic lightheadedness. The lightheadedness threshold, which marked the onset of lightheadedness, was equal to an average systolic CBFv decrease of 18.92% and end-tidal CO 2 of 12.82%. The intensity of lightheadedness was proportional to the CBFv and end-tidal CO 2 decline. Orthostatic lightheadedness correlated with systolic CBFv (r=-0.6, p < 0.001) and end-tidal CO 2 (r=-0.33, p < 0.001) decline. In conclusion, orthostatic CBFv and end-tidal CO 2 changes predict orthostatic lightheadedness and can be used as objective markers of OI.