Relationship between Bispectral Index Values and Volatile Anesthetic Concentrations during the Maintenance Phase of Anesthesia in the B-Unaware Trial

Abstract

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.

Recovery of consciousness is mediated by a network of discrete metastable activity states

“…For example, one consequence of the "stickiness" of the intermediates might be the relatively poor correlation between the depth-of-anesthesia monitor and the end-tidal anesthetic concentration in the B-Unaware trial (26). Another common feature when working with the available depth-of-anesthesia monitors is the occasional large jump with no apparent stimulation or change in anesthesia level, which might accord with a sudden state change with no precursor.…”

Impact of right‐handedness on anaesthetic sensitivity, intra‐operative awareness and postoperative mortality

“…Apart from accounting for within-patient repeated measures, a mixed effects model was appropriate for the analysis as it allows for missing and censored data, variable lengths of surgery and both fixed and random effects. Based on the findings of Whitlock et al [36], additional variables entered into the model included whether the individuals were categorised as ASA physical status 1-3 or > 3; male or female sex; age (< 60 or ≥ 60 years); administration of nitrous oxide (yes or no); administration of > 2 mg or ≤ 2 mg midazolam; administration of > 50 mg or ≤ 50 mg morphine equivalents and allocation to BIS-guided or ETAC-guided groups. For bivariable comparisons, we applied the chi-squared test, Fisher's exact test and Mann-Whitney U-test, as appropriate.…”

Comparing the Effect of Two Methods of Anesthesia Induction on Consciousness During Orthopedic Surgery

“…Certainly, electroencephalogram waves are affected by anesthesia and different wave patterns are observed during stages of anesthesia, which can be used processed or unprocessed/raw. Using the raw form is difficult because it is very complex and is influenced by artifacts, and its interpretation requires an experienced person [5].…”