EEG Quantitation of Narcotic Effect

Abstract

Fentanyl and alfentanil produce very similar EEG changes in humans. With increasing serum concentrations of either narcotic, progressive slowing in frequency occurs. This narcotic effect on the brain was quantitated using off-line EEG power spectrum analysis. During EEG recording, 6 unpremedicated patients received a fentanyl infusion (150 .mu.g/min), and 6 received alfentanil (1,500 .mu.g/min) until a specific level of EEG depression (.DELTA. waves) occurred. Timed arterial blood samples were obtained for measurement of the narcotic serum concentrations. The narcotic-induced EEG changes lag behind (in time) the serum narcotic concentration changes. To accurately relate EEG changes to serum narcotic concentrations, a pharmacodynamic model (inhibitory sigmoid Emax) was combined with a pharmacokinetic model that incorporated an effect compartment. (The effect compartment is the separate pharmacokinetic compartment where drug effect is directly proportional to drug concentration. It is the effect site). The magnitude of the time lag was quantitated by the half-time of equilibration between serum narcotic concentrations and concentrations in the effect compartment. With fentanyl, a significantly greater time lag was present (half-time = 6.4 .+-. 1.3 min; mean .+-. SD) than with alfentanil (half-time = 1.1 .+-. 0.3 min). This difference in time lag between blood concentration and effect may be due to the larger brain-blood partition coefficient for fentanyl. The steady-state serum concentration that caused one-half of the maximal EEG slowing was 6.9 .+-. 1.5 ng/ml for fentanyl, compared with 520 .+-. 163 ng/ml for alfentanil. Although fentanyl is reported to have a dose potency .apprx. 7 times that of alfentanil, the steady-state serum concentration potency ratio calculated from this study is .apprx. 75 to 1. This difference may be explained by alfentanil''s smaller initial distribution volume and by less time lag between serum concentration changes and changes in effect.