Responses of Processed Electroencephalographic Indices to Ascending and Descending Simulated Remimazolam Effect-Site Concentrations: A Prospective Exploratory Interventional Study
- 1Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea
- 2Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea
- 3Department of Anesthesiology and Pain Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu 41404, Republic of Korea
Abstract
Background/Objectives: Temporal characteristics of concentration–response loops for processed electroencephalographic indices during changes in remimazolam effect-site concentration (Ce) remain unclear. Therefore, this prospective, exploratory interventional study aims to compare the magnitude of concentration–response loops between the ascending and descending phases of simulated remimazolam Ce for the bispectral index (BIS) and patient state index (PSI). Methods: Twenty patients were administered remimazolam at a constant infusion rate of 3.5 mg/kg/h for 5.5 min, followed by infusion discontinuation. BIS and PSI values were continuously recorded from initiation of remimazolam infusion until 16 min, and remimazolam Ce was simulated using the Schüttler–Eisenried pharmacokinetic model. The area between the ascending and descending concentration–response curves (ABC) was calculated for each index within the overlapping Ce range. ABC was compared between BIS and PSI using a paired analysis, and a patient-level bootstrap was used to estimate the 95% confidence interval (CI) for the paired difference. Results: All 20 patients were included in the final analysis. The mean paired difference in ABC (BIS − PSI) was −6.254 (95% CI: −7.945 to −4.563), with a bootstrap median difference of −6.241 (95% CI: −8.752 to −4.133). The gap between the ascending and descending concentration–response curves was greater for PSI than for BIS. Conclusions: BIS and PSI showed different concentration–response patterns during changes in simulated remimazolam Ce, with PSI showing greater separation between the ascending and descending phases. These exploratory findings do not establish direct pharmacodynamic hysteresis or indicate superiority of BIS for assessing hypnotic state.
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BibTeX
@article{lee2026responses,
title = {{Responses of Processed Electroencephalographic Indices to Ascending and Descending Simulated Remimazolam Effect-Site Concentrations: A Prospective Exploratory Interventional Study}},
author = {Sou-Hyun Lee and Hyungjun Kwon and Seong Wook Hong and Hyun-Su Ri and Jung A Lim and Chanhyo Choi and Tae Hoon Kang and Hoon Jung and Kyung-Hwa Kwak},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15207905},
url = {https://www.mdpi.com/2077-0383/15/20/7905},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Responses of Processed Electroencephalographic Indices to Ascending and Descending Simulated Remimazolam Effect-Site Concentrations: A Prospective Exploratory Interventional Study
AU - Sou-Hyun Lee
AU - Hyungjun Kwon
AU - Seong Wook Hong
AU - Hyun-Su Ri
AU - Jung A Lim
AU - Chanhyo Choi
AU - Tae Hoon Kang
AU - Hoon Jung
AU - Kyung-Hwa Kwak
PY - 2026
DA - 2026/10/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15207905
UR - https://www.mdpi.com/2077-0383/15/20/7905
AB - Background/Objectives: Temporal characteristics of concentration–response loops for processed electroencephalographic indices during changes in remimazolam effect-site concentration (Ce) remain unclear. Therefore, this prospective, exploratory interventional study aims to compare the magnitude of concentration–response loops between the ascending and descending phases of simulated remimazolam Ce for the bispectral index (BIS) and patient state index (PSI). Methods: Twenty patients were administered remimazolam at a constant infusion rate of 3.5 mg/kg/h for 5.5 min, followed by infusion discontinuation. BIS and PSI values were continuously recorded from initiation of remimazolam infusion until 16 min, and remimazolam Ce was simulated using the Schüttler–Eisenried pharmacokinetic model. The area between the ascending and descending concentration–response curves (ABC) was calculated for each index within the overlapping Ce range. ABC was compared between BIS and PSI using a paired analysis, and a patient-level bootstrap was used to estimate the 95% confidence interval (CI) for the paired difference. Results: All 20 patients were included in the final analysis. The mean paired difference in ABC (BIS − PSI) was −6.254 (95% CI: −7.945 to −4.563), with a bootstrap median difference of −6.241 (95% CI: −8.752 to −4.133). The gap between the ascending and descending concentration–response curves was greater for PSI than for BIS. Conclusions: BIS and PSI showed different concentration–response patterns during changes in simulated remimazolam Ce, with PSI showing greater separation between the ascending and descending phases. These exploratory findings do not establish direct pharmacodynamic hysteresis or indicate superiority of BIS for assessing hypnotic state.
SN - 2077-0383
ER -