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

Gernot G Supp,Focko L Higgen,Joerg F Hipp,Markus Siegel,Andreas K Engel

doi:10.3389/fphar.2018.01427

Abstract

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.

Highlights

Worldwide, every year, more than 230 million patients are estimated to undergo anesthesia in the course of major surgical interventions (Weiser et al, 2008)
We found that increasing dosages of both, remifentanil and propofol progressively suppressed mid-latency Auditory evoked potentials (AEPs) (Figure 2)
We further characterized the drug effect on mid-latency AEPs by calculating the correlation between drug level and AEP for each subject and by testing for a consistent correlation across subjects. This revealed a negative correlation of AEPs with increasing drug level for remifentanil and propofol for both analytical approaches

Summary

Introduction

Every year, more than 230 million patients are estimated to undergo anesthesia in the course of major surgical interventions (Weiser et al, 2008). Auditory-evoked brain potentials (AEPs) are widely used to assess depth of the sedative component of general anesthesia. 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. 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

Results

Conclusion