Comparative Pharmacodynamic Modeling Using Bispectral and Narcotrend-Index With and Without a Pharmacodynamic Plateau During Sevoflurane Anesthesia

In Brief BACKGROUND: We compared two pharmacodynamic models, one with and one without a plateau effect. Bispectral indices (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend (NCT, MonitorTechnik, Bad Bramstedt, Germany, version 4.0) were used as an electroencephalographic measure of sevoflurane drug effect. In addition, we tried to analyze the origin of the plateau. METHODS: We investigated 26 adult patients scheduled for radical prostatectomy. At least 45 min after induction of general anesthesia, end-tidal sevoflurane concentrations were varied between 1 vol% and 4 vol%. To evaluate the relationship between concentrations and electroencephalographic indices, two different pharmacodynamic models were applied: a conventional model based on a single sigmoidal curve, and a novel model based on two sigmoidal curves for BIS and NCT values with and without burst suppression. The parameters of the models were estimated by NONMEM V (GloboMax, Hanover) by minimizing log likelihood. Statistical significance between the two models was calculated by the likelihood ratio test. RESULTS: The end-tidal sevoflurane concentration ranged from 1.04 ± 0.17 vol% to 4.43 ± 0.43 vol%. The difference between the log likelihood values of the new pharmacokinetic/pharmacodynamic model with two connected sigmoidal curves and the classical Emax model with one sigmoidal curve is 396 (P < 0.001) for the BIS monitor and 1121 (P < 0.001) for the NCT. The plateau is positioned at the change between the maximum δ power and the increase of burst suppression ratio. CONCLUSION: A pharmacokinetic/pharmacodynamic model consisting of two sigmoid curves with an intervening plateau describes the effect of sevoflurane on BIS and NCT indices better than a model with a single sigmoid curve. IMPLICATIONS: A pharmacokinetic/pharmacodynamic model with two sigmoidal curves connected by a intervening plateau describes the effect of sevoflurane on Bispectral Index and Narcotrend indices better than the classical Emax model with a single sigmoid curve. This new model might have advantages in studies where higher doses could result in electroencephalographic burst suppression.