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Individualizing arterial blood pressure (ABP) targets during cardiopulmonary bypass (CPB) based on cerebral blood flow (CBF) autoregulation monitoring may provide a more effective means for preventing cerebral hypoperfusion than the current standard of care. Autoregulation can be monitored in real time with transcranial Doppler (TCD). We have previously demonstrated that near-infrared spectroscopy (NIRS)–derived regional cerebral oxygen saturation (rScO2) provides a clinically suitable surrogate of CBF for autoregulation monitoring. The purpose of this study was to determine the accuracy of a stand-alone “plug-and-play” investigational system for autoregulation monitoring that uses a commercially available NIRS monitor with TCD methods.TCD monitoring of middle cerebral artery CBF velocity and NIRS monitoring were performed in 70 patients during CPB. Indices of autoregulation were computed by both a personal computer–based system and an investigational prototype NIRS-based monitor. A moving linear correlation coefficient between slow waves of ABP and CBF velocity (mean velocity index [Mx]) and between ABP and rScO2 (cerebral oximetry index [COx]) were calculated. When CBF is autoregulated, there is no correlation between CBF and ABP; when CBF is dysregulated, Mx and COx approach 1 (i.e., CBF and ABP are correlated). Linear regression and bias analysis were performed between time-averaged values of Mx and COx derived from the personal computer–based system and from COx measured with the prototype monitor. Values for Mx and COx were categorized in 5 mm Hg bins of ABP for each patient. The lower limit of CBF autoregulation was defined as the ABP where Mx incrementally increased to ≥0.4.There was correlation and good agreement between COx derived from the prototype monitor and Mx (r = 0.510; 95% confidence interval, 0.414–0.595; P < 0.001; bias, –0.07 ± 0.19). The correlation and bias between the personal computer–based COx and the COx from the prototype NIRS monitor were r = 0.957 (95% confidence interval, 0.945–0.966; P < 0.001 and 0.06 ± 0.06, respectively). The average ABP at the lower limit of autoregulation was 63 ± 11 mm Hg (95% prediction interval, 52–74 mm Hg). Although the mean ABP at the COx-determined lower limit of autoregulation determined with the prototype monitor was statistically different from that determined by Mx (59 ± 9 mm Hg; 95% prediction interval, 50–68 mm Hg; P = 0.026), the difference was not likely clinically meaningful.Monitoring CBF autoregulation with an investigational stand-alone NIRS monitor is correlated and in good agreement with TCD-based methods. The availability of such a device would allow widespread autoregulation monitoring as a means of individualizing ABP targets during CPB.