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Background:  Auditory-evoked brain potentials (AEPs) are widely used to assess depth of the sedative component of general anesthesia. Depth of sedation as induced by hypnotic drugs (e.g., propofol) is characterized by a gradual decline of mid-latency cortical AEPs (10–50 ms). Using the decline of mid-latency AEPs as a reliable index for sedation requires its robustness against confounding pharmaceutical influences, e.g., analgesic opioids such as remifentanil. Critically, in this context the following two questions remained unresolved so far: First, it is unclear whether opioids directly affect mid-latency AEPs. Second, high doses of opioids decrease arousal, but it is unknown whether opioid-induced sedation is reflected by the diminution of mid-latency AEPs. We hypothesized that opioids affect mid-latency AEPs and that these effects rely on different mechanisms compared to hypnotic agents.   Methods:  To address both questions, we performed a series of experiments under the participation of healthy human volunteers. We measured AEPs and quantified participants’ sedation state by a standardized rating scale during stepwise increase of different pharmaceutical agents (remifentanil, propofol or placebo).   Results:  Our results revealed a decline of mid-latency AEPs during remifentanil medication. This decrease was predicted by drug dose, rather than sedation level. In contrast, attenuation of the mid-latency AEPs during propofol was predicted by sedation level and was not related to hypnotic drug dose. We did not find any drug-induced changes of brainstem AEPs (1–10 ms).   Conclusion:  As remifentanil reduced mid-latency AEPs without inducing strong sedation levels, a decrease of this evoked brain component does not constitute an unequivocal index for the depth of sedation. These results challenge the use of mid-latency AEPs as a reliable marker of depth of the sedative component of anesthesia if hypnotic drugs are combined with opioids.

Mid-Latency Auditory Evoked Potentials Differentially Predict Sedation and Drug Level Under Opioid and Hypnotic Agents