Background: Delayed emergence from anaesthesia presents clinical challenges, including prolonged stays in the post-anaesthesia care unit (PACU). The neurobiological mechanisms underlying delayed emergence, particularly in remimazolam-induced anaesthesia, remain poorly understood. This study aimed to elucidate these mechanisms by comparing remimazolam and propofol anaesthesia, focusing on prefrontal electroencephalogram (EEG). Methods: Patients (age > 18, n = 48) underwent laparoscopic cholecystectomy randomly received remimazolam or propofol general anaesthesia. Power spectrogram analysis and functional connectivity measures, phase lag entropy (PLE) and phase lag index (PLI), were employed to the prefrontal EEG data collected at baseline, unconsciousness, and emergence. Correlation between EEG measures and Patient State Index (PSI) at PACU, as well as time to Aldrete 9, were compared. Results: PSI values (P < 0.0001, P = 0.006) and time to Aldrete 9 at PACU (P < 0.001) revealed slower recovery in remimazolam-induced anaesthesia. Remimazolam group exhibited residual effects in power at theta (P = 0.018) and alpha (Ps < 0.001) bands and lower PLE during emergence in the alpha (P < 0.0001, P = 0.015) and beta (P = 0.016, P < 0.001) bands. Delayed consciousness recovery (time to Aldrete 9) under remimazolam was significantly correlated with PLE (Pearson's r = -.78, P < 0.0001), and PLI (Pearson's r = .69, P = 0.028) in the alpha band during deep anaesthesia. Conclusion: Dynamic changes in prefrontal EEG and the correlation analyses show the potential of EEG in predicting emergence speed, providing insights into the neurobiological mechanisms of short-term delayed emergence in remimazolam anaesthesia.

The authors have declared no competing interest.

This study was supported by IBS-R015-Y3 and by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2023R1A2C1006054 to Bon-Nyeo Koo).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The institutional review board of Severance Hospital, Yonsei University Health System (Chairperson Prof Dr. Young Guk Ko, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Korea; 06/12/2021) gave ethical approval for this work (IRB # 4-2022-1405).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study is not open and is not available to the public.