We did not reproduce the results of previous studies that reported a lower incidence of anesthesia awareness with BIS monitoring, and the use of the BIS protocol was not associated with reduced administration of volatile anesthetic gases. Anesthesia awareness occurred even when BIS values and ETAG concentrations were within the target ranges. Our findings do not support routine BIS monitoring as part of standard practice. (ClinicalTrials.gov number, NCT00281489 [ClinicalTrials.gov].).

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This study found an association between cumulative duration of low BIS and mortality in the setting of cardiac surgery. Notably, this association was independent of both volatile anesthetic concentration and duration of anesthesia, suggesting that intermediate-term mortality after cardiac surgery was not causally related to excessive anesthetic dose.

Background Hypnotic depth during anesthesia affects electroencephalography waveforms and electroencephalogram-derived indices, such as the bispectral index (BIS). Titrating anesthetic administration against the BIS assumes reliable relationships between BIS values, electroencephalogram waveforms, and effect site concentration, beyond loss of responsiveness. Associations among BIS, end-tidal anesthetic concentrations (ETAC), and patient characteristics were examined during anesthetic maintenance, using B-Unaware trial data. Methods Pharmacokinetically stable ETAC epochs during intraoperative anesthetic maintenance were analyzed. A generalized estimating equation determined independent relationships among BIS, ETAC (in age-adjusted minimum alveolar concentration equivalents), patient characteristics and 1-year mortality. Further individual and population characteristics were explored graphically. Results 3,347,523 data points from 1,100 patients were analyzed over an ETAC range from 0.42 to 1.51 age-adjusted minimum alveolar concentration. A generalized estimating equation yielded a best predictive equation: BIS = 62.9 – 1.6 (if age<60) – 1.6 (if female) – 2.5 (if American Society of Anesthesiologists physical status >3) - 2.6 (if deceased at 1 year) - 2.5 (if nitrous oxide was not used) – 1.4 (if midazolam dose >2mg) – 1.3 (if opioid dose >50 morphine equivalents) - 15.4* age-adjusted minimum alveolar concentration. Although a population relationship between ETAC and BIS was apparent, inter-individual variability in the strength and reliability of this relationship was large. Decreases in BIS with increasing ETAC were not reliably observed. Individual-patient linear regression yielded a median slope of −8 BIS/ 1 age-adjusted minimum alveolar concentration (interquartile range −30, 0) and a median correlation coefficient of −0.16 (interquartile range −0.031, −0.50). Conclusions Independent of pharmacokinetic confounding, BIS frequently correlates poorly with ETAC, is often insensitive to clinically significant changes in ETAC, and is vulnerable to inter-individual variability. BIS is therefore incapable of finely guiding volatile anesthetic titration during anesthetic maintenance.

Background: Postoperative mortality has been associated with cumulative anesthetic duration below an arbitrary processed electroencephalographic threshold (bispectral index [BIS] Ͻ45). This substudy of the B-Unaware Trial tested whether cumulative duration of BIS values lower than 45, cumulative anesthetic dose, comorbidities, or intraoperative events were independently associated with postoperative mortality. Methods: The authors studied 1,473 patients (mean Ϯ SD age, 57.9 Ϯ 14.4 yr; 749 men) who underwent noncardiac surgery at Barnes-Jewish Hospital in St. Louis, Missouri. Multivariable Cox regression analysis was used to determine whether perioperative factors were independently associated with all-cause mortality. Results: A total of 358 patients (24.3%) died during a follow-up of 3.2 Ϯ 1.1 yr. There were statistically significant associations among various perioperative risk factors, including malignancy and intermediate-term mortality. BIS-monitored patients did not have lower mortality than unmonitored patients (24.9 vs. 23.7%; difference ϭ 1.2%, 95% CI, Ϫ3.3 to 5.6%). Cumulative duration of BIS values less than 45 was not associated with mortality (multivariable hazard