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This study was conducted to compare the performance accuracy of the independent variables Bispectral Index (BIS), A-Line ARX index (AAI), and predicted propofol effect-site concentration (CePROP) to measure the dependent variables of loss of responses to different stimulation defined as loss of response to verbal command (LORverbal), eyelash reflex (LORlash), and noxious stimulus (LORnoxious) during stepwise increased levels of propofol infusion with and without remifentanil.Forty-five patients were randomly allocated to one of three groups (0, 2, and 4 ng/ml remifentanil) to receive graded CePROP and predicted effect compartment controlled remifentanil (CeREMI). At every step, the ability to respond to verbal command using the Observer's Assessment of Alertness/Sedation Scale (OAA/S), eyelash reflex, and electrical tetanic noxious stimulus were compared against BIS, AAI, and CePROP. Prediction probability and sensitivity/specificity were calculated.Increasing CeREMI increased BIS and AAI values at LORverbal and LORlash and decreased CePROP. Similar findings were found for LORnoxious. The overall prediction probability to measure the hypnotic component of anesthesia remained accurate in the three groups for BIS, AAI, and CePROP. Combined information from CePROP, CeREMI, and BIS or AAI increased the overall prediction probability for predicting the OAA/S scale and LORlash. Less accuracy to LORnoxious was found in all independent variables.Although BIS, AAI, and CePROP were influenced by remifentanil during propofol administration, their ability to detect OAA/S and LORlash remained accurate. Improved performance is obtained when BIS and AAI are measured in conjunction with drug targeted effect-site concentrations. Remifentanil decreases the ability of these independent variables to detect LORnoxious.