OBJECTIVE: To develop a simple and reliable method for quantitating plasma glutamate concentration and apply this method to monitor systemic glutamate levels during coronary artery bypass graft (CABG) surgery, a procedure associated with neurologic deficits. DESIGN: Prospective serial investigation of cardiac surgery patients. SETTING: Tertiary-care university teaching hospital. PARTICIPANTS: Patients undergoing CABG surgery (n = 33). INTERVENTIONS: Preoperative and postoperative neurologic and neurocognitive testing were done. Intraoperative blood samples for glutamate quantitation were obtained from jugular bulb and pulmonary artery catheters before, during, and after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Glutamate concentrations were determined using a reverse-phase high-pressure liquid chromatography method coupled to precolumn derivatization of the analyte with o-phthalaldehyde. The mean prebypass plasma glutamate concentration was 79.4 +/- 41.8 micromol/L. Plasma glutamate levels fluctuated during surgery with considerable degrees of temporal and quantitative interpatient variability. Neurologic and neurocognitive deficits were observed after CABG surgery. However, neither the occurrence nor the severity of cognitive decline could be predicted by the magnitude of increase in plasma glutamate concentration. CONCLUSION: Fluctuations in intraoperative systemic glutamate levels do not predict post-CABG surgery neurologic outcome.