BISPECTRAL ANALYSIS MEASURES SEDATION AND MEMORY EFFECTS OF PROPOFOL,MIDAZOLAM, ISOFLURANE, AND ALFENTANIL IN HEALTHY-VOLUNTEERS

Background The bispectral index (BIS), a value derived from the electr oencephalograph (EEG), has been proposed as a measure of anesthetic ef fect. To establish its utility for this purpose, it is important to de termine the relation among BIS, measured drug concentration, and incre asing levels of sedation. This study was designed to evaluate this rel ation for four commonly used anesthetic drugs: propofol, midazolam, is oflurane, and alfentanil. Methods: Seventy-two consenting volunteers w ere studied at four institutions. Volunteers were given either isoflur ane, propofol, midazolam, or alfentanil. Each volunteer was administer ed a dose-ranging sequence of one of the study drugs to achieve predet ermined target concentrations. A frontal montage was used for continuo us recording of the EEG. At each pseudo--steady-state drug concentrati on, a BIS score was recorded, the participant was shown either a pictu re or given a word to recall, an arterial blood sample was obtained fo r subsequent analysis of drug concentration, and the participant was e valuated for level of sedation as determined by the responsiveness por tion of the observer's assessment of the alertness/sedation scale (OAA S). An OAAS score of 2 or less was considered unconscious. The BIS (ve rsion 2.5) score was recorded in real-time and the BIS (version 3.0) w as subsequently derived off-line from the recorded raw EEG data. The r elation among BIS, measured drug concentration, responsiveness score, and presence or absence of recall was determined by linear and logisti c regression for both the individual drugs and, when appropriate, for the pooled results. The prediction probability was also calculated. Re sults: The BIS score (r = 0.883) correlated significantly better than the measured propofol concentration (r = -0.778; P < 0.05) with the re sponsiveness score. The BIS provided as effective correlation with res ponsiveness score of the OAAS as did the measured concentration for mi dazolam and isoflurane. None of the volunteers given alfentanil lost c onsciousness and thus were excluded from the pooled analysis. The pool ed BIS values at which 50% and 95%, of participants were unconscious w ere 67 and 50, respectively. The prediction probability values for BIS ranged from 0.885-0.976, indicating a very high predictive performanc e for correctly Indicating probability of loss of consciousness. Concl usions: The BIS both correlated well with the level of responsiveness and provided an excellent prediction of the loss of consciousness. The se results imply that BIS may be a valuable monitor of the level of se dation and loss of consciousness for propofol, midazolam, and isoflura ne.