Characterization of the Bispectral Index in Healthy Volunteers Receiving Inhalation Anesthetics in Combination With Opioids in a Randomized Trial

BACKGROUND: Processed electroencephalogram (pEEG) monitors are commonly used in anesthesia practice. The relationship between the pEEG and clinical levels of sedation over anesthetic concentrations with and without opioids is not well understood. The purpose of this trial was to investigate the relationship between Bispectral Index TM (BIS TM ), clinical measures of sedation, and inhaled anesthetics across a range of anesthetic concentrations and hypnotic states with and without intravenous opioids. METHODS: This prospective, randomized trial enrolled 211 healthy volunteers. Participants were randomized to one of five anesthetic regimens: sevoflurane, sevoflurane with remifentanil, sevoflurane with fentanyl, desflurane, or isoflurane. Target anesthetic end-tidal concentrations were increased in a stepwise fashion until a BIS index of 30 to 40 was reached. Opioids were administered by target-controlled infusion and commenced before the inhaled agent began. At each targeted end-tidal concentration, responsiveness was assessed using the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score and the BIS index was recorded. The MOAA/S score was used to assess participant responsiveness, with a score ≤2 considered unresponsive and a score ≥3 considered responsive. The primary outcome measure was the BIS 50 for each anesthetic regimen, representing the BIS index at which 50% of participants were unresponsive. Secondary outcomes included BIS 95 (representing the BIS index at which 95% of participants were unresponsive) and evaluation of the BIS index as a predictor of responsiveness. BIS 50 and BIS 95 were estimated using random intercept logistic regression models, and the predictive performance of BIS indices was assessed by calculating the corresponding area under the receiver operating characteristic curve (AUC). RESULTS: One hundred and forty-three participants were randomized to a treatment group and completed the procedure with adequate data. Mean age was 26.5 ± 6.7 years (52% male). There were no reported device-related adverse events. Across treatment groups, BIS 50 ranged from 67.5 (95% confidence interval [CI], 63.6–71.4) to 76.2 (73.5–78.8), and BIS 95 ranged from 49.1 (42.9–55.4) to 63.3 (59.5–67.2). Compared to the sevoflurane and isoflurane groups, the desflurane group exhibited slightly lower BIS 50 and BIS 95 values. The addition of opioids to sevoflurane had minimal impact on BIS 50 and BIS 95 . The BIS index alone was a strong predictor of the level of responsiveness, with AUCs consistently close to the ideal value of 1 (≥0.95) across all treatment groups. BIS indices were highly correlated with MOAA/S scores. CONCLUSIONS: These results describe the relationship between BIS levels and responsiveness for commonly used volatile anesthetics, with and without opioids, across a range of anesthetic concentrations. The results of this study should be interpreted in light of the study design which included young, healthy adult volunteers with no sustained, noxious stimulation. These findings may not be generalizable to other populations or clinical situations.