Seongheon Lee 1,2, Jeongil Choi 1,2, Dongho Kang 1, Yechan Yoo 1, Seongwook Jeong 1,2
1 Chonnam University Hwasun Hospital (Hwasun, S.Korea), 2 Chonnam University Medical School (Gwangju, S. Korea)
Objectives:
Electroencephalography (EEG)-derived indices are widely used to titrate volatile anesthetics, yet pharmacodynamic (PD) characterization and head-to-head comparisons for newer indices remain limited. The anesthetic depth monitoring for sedation (ADMS) index uses an algorithm identical to qCON and is increasingly used in clinical practice. We aimed to (i) characterize the end-tidal sevoflurane concentration (EtSevo)–effect relationship for ADMS and BIS using population PD modeling with an effect-site link, and (ii) evaluate agreement and dynamic performance of ADMS relative to BIS across controlled intraoperative concentration changes and clinically relevant perioperative time points.
Methods:
In this prospective exploratory study, adult patients undergoing elective laparoscopic gastrectomy under sevoflurane anesthesia were monitored simultaneously with ADMS and BIS. A standardized protocol cycled EtSevo between 1.0 and 4.0 vol% in two up–down ramp sequences during stable surgical conditions. ADMS and BIS were recorded at 1-s intervals and downsampled to 10-s to match EtSevo sampling; epochs with signal quality index <50 were excluded. For each index, an inhibitory sigmoidal Emax model linked to an effect-site compartment (Ke0) was fitted using nonlinear mixed-effects modeling (NONMEM). Agreement between paired measurements was assessed by linear regression and Bland–Altman analysis. Dynamic performance of ADMS relative to BIS was quantified using Varvel metrics (MDPE, MDAPE, wobble, divergence), treating BIS as the reference index. Index values at predefined time points (before induction, loss of consciousness [LOC], return of consciousness [ROC]) were compared using paired tests.
Results:
Twenty-nine patients were included in the final analysis. Both indices exhibited inverse sigmoidal EtSevo–effect relationships with broadly similar typical PD parameters. Estimated typical values (ADMS vs BIS) were: baseline E0 49.6 vs 51.3, Emax 18.8 vs 17.0, CE50 1.86 vs 1.69 vol%, Hill coefficient 13.9 vs 17.4, and Ke0 0.118 vs 0.148 min⁻¹. Interindividual variability was substantial, particularly for Emax and Ke0 (approximately 55–124%CV). Residual unexplained variability was larger for ADMS than BIS (additive SD 22.7 vs 15.5), consistent with a noisier signal under the study conditions. Across all paired ramp-sequence measurements, ADMS and BIS showed moderate correlation (R² = 0.425). Bland–Altman analysis demonstrated a mean bias (ADMS − BIS) of −4.18 points with 95% limits of agreement from −20.74 to 12.38. Varvel metrics indicated modest negative bias and moderate inaccuracy of ADMS relative to BIS (MDPE −12.8% [IQR −16.7 to −7.63], MDAPE 18.1% [14.3 to 21.9], wobble 12.1% [10.4 to 14.0], divergence −0.181%/h [−0.641 to 0.456]), suggesting no systematic time-related drift. At perioperative time points, ADMS and BIS did not differ significantly: before induction 91.6 vs 90.7, at LOC 86.3 vs 85.0, and at ROC 77.7 vs 81.3 (all P>0.05). No explicit recall of intraoperative events was reported in postoperative interviews.
Conclusions:
During sevoflurane anesthesia, the ADMS (qCON-based) index demonstrated concentration–effect behavior and effect-site equilibration broadly comparable to BIS at the population level. However, only moderate correlation, relatively wide limits of agreement, and higher residual variability indicate potentially meaningful divergence at the individual-measurement level. These findings support ADMS as a clinically useful EEG-derived hypnotic index, while suggesting it should be interpreted judiciously when considered as a direct replacement for BIS, and that monitor-specific thresholds may be required for individual patient management.
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References
[1] Olofsen E, Dahan A. The dynamic relationship between end-tidal sevoflurane concentrations and EEG measures. Anesthesiology. 1999;90:1345–1353.
[2] Varvel JR, Donoho DL, Shafer SL. Measuring predictive performance of computer-controlled infusion pumps. J Pharmacokinet Biopharm. 1992;20:63–94.
[3] Kim DH, Yoo JY, Kim JY, et al. Electrocautery-induced interference: ADMS vs BIS. Korean J Anesthesiol. 2018;71:368–373.
Reference: PAGE 34 (2026) Abstr 11959 [www.page-meeting.org/?abstract=11959]
Poster: Drug/Disease Modelling - Other Topics