Relationships between quantitative EEG measures and pharmacodynamics of alfentanil in dogs

Intravenous alfentanil was administered as a constant 1 h infusion to 6 dogs. Before, during and up to 3 h after infusion, the effects of 3 doses (0.001, 0.004 and 0.016 mg/kg/min) on 6 quantitative EEG measures (zero-crossing frequency, root mean square (rms) amplitude, spectral edge, relative delta, alpha and beta power) were assessed in relation to plasma concentrations of alfentanil. All EEG measures, except zero-crossing frequency and rms amplitude, showed statistically significant dose-dependent changes in peak effect and duration. In addition, times-to-peak effect and return-to-baseline were sensitive to dose. The EEG effects of the low dose were smaller than those of the middle and high doses, whose peak effects did not statistically differ; but the high dose produced more persistent effects, which outlasted the infusion period for a longer time. Alfentanil-induced changes in rms amplitude and relative delta power showed the widest dynamic ranges. Measurable EEG changes occurred at low plasma concentrations, but EEG responses saturated at the middle dose. Significant correlations between plasma concentration and EEG effect were obtained for only the subperiod ranging from onset of infusion to peak EEG effect, indicating very short concentration-effect equilibration delays. On the other hand, clockwise concentration-effect loops were suggestive of acute tolerance: EEG responses peaked before peak plasma levels and they returned to baseline at dose-dependently higher plasma concentrations of alfentanil.