Comparison of the concentration-dependent effect of sevoflurane on the spinal H-reflex and the EEG in humans.

Abstract

It has been shown that spinal reflexes such as the H-reflex predict motor responses to painful stimuli better than cortical parameters derived from the EEG. The precise concentration-dependence of H-reflex suppression by anaesthetics, however, is not known. Here we investigated this concentration-response relationship and the equilibration between the alveolar and the effect compartment for sevoflurane. In 26 patients, the H-reflex was recorded at a frequency of 0.1 Hz while anaesthesia was induced and maintained with sevoflurane at increasing and decreasing concentrations. Population pharmacodynamic modelling was performed using the NONMEM software package, yielding population mean parameters as well as indicators of interindividual variability. Suppression of H-reflex amplitude occurred at lower concentrations (mean EC(50) 1.04 +/- 0.10 vol%, SE of NONMEM estimate) than the effect on either BIS or SEF(95) of the EEG (mean EC(50) 1.55 +/- 0.08 and 1.72 +/- 0.18 vol%, respectively), and exhibited a higher interindividual variability. The concentration-response function for the H-reflex was also steeper (mean ë 2.83 +/- 0.25). In addition, the equilibration between alveolar and effect compartment was slower for the H-reflex (mean k(e0) 0.15 +/- 0.01 min(-1)) than for BIS or SEF(95) (mean k(e0) 0.22 +/- 0.02 and 0.41 +/- 0.05 min(-1)). The differences in EC(50) and slope of the concentration-response relationships for H-reflex suppression and the EEG parameters point to different underlying mechanisms. In addition, the differences in time constant for equilibration between alveolar and effect compartment confirm the notion that immobility is caused at a different anatomic site than suppression of the EEG.