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Mean arterial blood pressure (MAP) targets are empirically chosen during cardiopulmonary bypass (CPB). We have previously shown that near-infrared spectroscopy (NIRS) can be used clinically for monitoring cerebral blood flow autoregulation. The hypothesis of this study was that real-time autoregulation monitoring using NIRS-based methods is more accurate for delineating the MAP at the lower limit of autoregulation (LLA) during CPB than empiric determinations based on age, preoperative history, and preoperative blood pressure.Two hundred thirty-two patients undergoing coronary artery bypass graft and/or valve surgery with CPB underwent transcranial Doppler monitoring of the middle cerebral arteries and NIRS monitoring. A continuous, moving Pearson correlation coefficient was calculated between MAP and cerebral blood flow velocity and between MAP and NIRS data to generate mean velocity index and cerebral oximeter index. When autoregulated, there is no correlation between cerebral blood flow and MAP (i.e., mean velocity and cerebral oximetry indices approach 0); when MAP is below the LLA, mean velocity and cerebral oximetry indices approach 1. The LLA was defined as the MAP at which mean velocity index increased with declining MAP to ≥0.4. Linear regression was performed to assess the relation between preoperative systolic blood pressure, MAP, MAP in 10% decrements from baseline, and average cerebral oximetry index with MAP at the LLA.The MAP at the LLA was 66 mm Hg (95% prediction interval, 43 to 90 mm Hg) for the 225 patients in which this limit was observed. There was no relationship between preoperative MAP and the LLA (P = 0.829) after adjusting for age, gender, prior stroke, diabetes, and hypertension, but a cerebral oximetry index value of >0.5 was associated with the LLA (P = 0.022). The LLA could be identified with cerebral oximetry index in 219 (94.4%) patients. The mean difference in the LLA for mean velocity index versus cerebral oximetry index was −0.2 ± 10.2 mm Hg (95% CI, −1.5 to 1.2 mm Hg). Preoperative systolic blood pressure was associated with a higher LLA (P = 0.046) but only for those with systolic blood pressure ≤160 mm Hg.There is a wide range of MAP at the LLA in patients during CPB, making estimation of this target difficult. Real-time monitoring of autoregulation with cerebral oximetry index may provide a more rational means for individualizing MAP during CPB.