GABAA circuit mechanisms are associated with ether anesthesia-induced unconsciousness

• Large amplitude slow oscillations, frontally coherent theta oscillations and frontally coherent alpha oscillations occur during general anesthesia induced with modern day derivatives of ether (MDDE).
• Reduction of GABAergic inhibitory post-synaptic potentials with ketamine resulted in beta/gamma (13–40 Hz) oscillations and significantly reduced MDDE anesthesia-induced slow, theta and alpha oscillation power.
• GABAA circuit-level mechanisms are associated with MDDE anesthesia-induced unconsciousness.

ObjectiveAn emerging paradigm for understanding how anesthetics induce altered arousal is relating receptor targeting in specific neural circuits to electroencephalogram (EEG) activity. Enhanced gamma amino-butyric acid A (GABAA) inhibitory post-synaptic currents (IPSCs) manifest with large-amplitude slow (0.1–1 Hz) and frontally coherent alpha (8–12 Hz) EEG oscillations during general anesthesia. Therefore, we investigated the EEG signatures of modern day derivatives of ether (MDDE) anesthesia to assess the extent to which we could obtain insights into MDDE anesthetic mechanisms.MethodsWe retrospectively studied cases from our database in which patients received isoflurane anesthesia vs. isoflurane/ketamine anesthesia (n = 10 each) or desflurane anesthesia vs. desflurane/ketamine anesthesia (n = 9 each). We analyzed the EEG recordings with spectral power and coherence methods.ResultsSimilar to known GABAA circuit level mechanisms, we found that MDDE anesthesia induced large amplitude slow and frontally coherent alpha oscillations. Additionally, MDDE anesthesia also induced frontally coherent theta (4–8 Hz) oscillations. Reduction of GABAergic IPSCs with ketamine resulted in beta/gamma (13–40 Hz) oscillations, and significantly reduced MDDE anesthesia-induced slow, theta and alpha oscillation power.ConclusionsLarge amplitude slow oscillations and coherent alpha and theta oscillations are moderated by ketamine during MDDE anesthesia.SignificanceThese observations are consistent with the notion that GABAA circuit-level mechanisms are associated with MDDE anesthesia-induced unconsciousness.