Intra- and inter-individual variation of BIS-index (R) and Entropy (R) during controlled sedation with midazolam/remifentanil and dexmedetomidine/remifentanil in healthy volunteers: an interventional study

Introduction We studied intra-individual and inter-individual variability of two online sedation monitors, BIS (R) and Entropy (R), in volunteers under sedation. Methods Ten healthy volunteers were sedated in a stepwise manner with doses of either midazolam and remifentanil or dexmedetomidine and remifentanil. One week later the procedure was repeated with the remaining drug combination. The doses were adjusted to achieve three different sedation levels (Ramsay Scores 2, 3 and 4) and controlled by a computer-driven drug-delivery system to maintain stable plasma concentrations of the drugs. At each level of sedation, BIS (R) and Entropy (R) (response entropy and state entropy) values were recorded for 20 minutes. Baseline recordings were obtained before the sedative medications were administered. Results Both inter-individual and intra-individual variability increased as the sedation level deepened. Entropy (R) values showed greater variability than BIS (R) values, and the variability was greater during dexmedetomidine/remifentanil sedation than during midazolam/remifentanil sedation. Conclusions The large intra-individual and inter-individual variability of BIS (R) and Entropy (R) values in sedated volunteers makes the determination of sedation levels by processed electroencephalogram (EEG) variables impossible. Reports in the literature which draw conclusions based on processed EEG variables obtained from sedated intensive care unit (ICU) patients may be inaccurate due to this variability. Trial registration clinicaltrials. gov Nr. NCT00641563.