Electroencephalographic response following midazolam-induced general anesthesia: relationship to plasma and effect-site midazolam concentrations

Miyake, Wakako; Oda, Yutaka; Ikeda, Yuko; Hagihira, Satoshi; Iwaki, Hiroyoshi; Asada, Akira
June 2010
Journal of Anesthesia;2010, Vol. 24 Issue 3, p386
Academic Journal
To examine the relationships between effect-site concentrations and electroencephalographic parameters after the induction of general anesthesia with midazolam. Twenty-four patients with American Society of Anesthesiologists status I or II were randomly allocated to receive either an intravenous (i.v.) bolus of midazolam 0.2 mg kg−1 (small-dose group, n = 12) or 0.3 mg kg−1 (large-dose group, n = 12) for induction of general anesthesia in a double-blind experimental design. The bispectral index (BIS), 95% spectral edge frequency (SEF95), spectral power density, and plasma concentrations of midazolam were measured for 60 min following the induction of general anesthesia. Plasma and simulated effect-site concentrations of midazolam were significantly higher in the large-dose group than in the small-dose group ( P = 0.005 and <0.001, respectively). There was a correlation between the relative beta ratio and BIS ( r2 = 0.30, P < 0.001; n = 168); however, effect-site concentrations of midazolam showed no association with BIS, relative beta ratio, or SEF95 ( r2 = 0.07, 0.11 and 0.01, respectively; n = 168). The electroencephalographic spectral power density in the beta-band (≥13 and <30 Hz) was significantly increased after induction and was significantly larger in the large-dose group than in the small-dose group ( P = 0.009). Following the induction of general anesthesia with i.v. midazolam 0.2 or 0.3 mg kg−1, the BIS was positively correlated with the relative beta ratio. Despite a rapid decrease in the plasma and effect-site concentrations of midazolam, the average BIS remained >60 for 60 min after induction, reflecting an increased power of the electroencephalographic high-frequency band.


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