Schreier David R, Fecchio Matteo, Guay Christian S, Kovacs Reid G, Olchanyi Mark, Mueller Ariel L, Houle Timothy T, Edlow Brian L, Brown Emery N, Solt Ken
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nat Sci Sleep. 2025 Jun 12;17:1259-1269. doi: 10.2147/NSS.S523111. eCollection 2025.
Dexmedetomidine (DEX) is a well-tolerated sedative drug that induces a sleep-like state. DEX sedation offers a model to study transitions between different states of consciousness (indicated by, eg, behavior, the electroencephalogram (EEG), or transcranial magnetic stimulation (TMS) evoked EEG responses). However, the effects of repeated DEX exposure on recovery are poorly understood and will be investigated in this pilot study.
We aim to enroll 12 healthy volunteers (6 females, 6 males). Although we do not expect TMS-EEG to interfere with DEX sedation, due to the paucity of evidence this study uses a parallel arm design (TMS-EEG, non-TMS-EEG). Participants will be sedated twice, one week apart, and responsiveness monitored by a click-task to auditory beeps. A 64-channel EEG and additional physiological signals will be recorded. Cognition and vigilance tests will be performed before sedation (baseline), after return of responsiveness (ROR), and before discharge. TMS-EEG will be performed at baseline, during sedation, and during recovery. Using a smartwatch and questionnaires, we will assess sleep quality, sleepiness, and experiences during sedation and TMS-EEG.
We will report the difference of time to ROR between the first and second study visit, and explore potential differences across sex and study arms. We will evaluate state transitions by comparing responsiveness, traditional EEG signatures, TMS-evoked EEG responses (ie, perturbational complexity index), and report on cognition and vigilance test performance.
This pilot trial will report on the effect of repeated DEX exposure on the recovery period, and the investigation of state transitions will advance our scientific understanding of altered states of consciousness. REDEX will provide valuable insights and data for designing future DEX sedation studies. Moreover, we will report on the potential of biological sex as a confounding factor and the feasibility of TMS-EEG under DEX.
右美托咪定（DEX）是一种耐受性良好的镇静药物，可诱导类似睡眠的状态。DEX镇静提供了一个模型，用于研究不同意识状态之间的转换（例如通过行为、脑电图（EEG）或经颅磁刺激（TMS）诱发的EEG反应来指示）。然而，重复使用DEX对恢复的影响了解甚少，本初步研究将对此进行调查。
我们旨在招募12名健康志愿者（6名女性，6名男性）。尽管我们预计TMS-EEG不会干扰DEX镇静，但由于证据不足，本研究采用平行组设计（TMS-EEG组、非TMS-EEG组）。参与者将接受两次镇静，间隔一周，通过对听觉哔哔声的点击任务监测反应性。将记录64通道EEG和其他生理信号。在镇静前（基线）、反应性恢复后（ROR）和出院前进行认知和警觉性测试。TMS-EEG将在基线、镇静期间和恢复期间进行。我们将使用智能手表和问卷评估睡眠质量、嗜睡程度以及镇静和TMS-EEG期间的体验。
我们将报告首次和第二次研究访视之间ROR时间的差异，并探索性别和研究组之间的潜在差异。我们将通过比较反应性、传统EEG特征、TMS诱发的EEG反应（即微扰复杂性指数）来评估状态转换，并报告认知和警觉性测试表现。
这项初步试验将报告重复使用DEX对恢复期的影响，对状态转换的研究将推进我们对意识改变状态的科学理解。REDEX将为设计未来的DEX镇静研究提供有价值的见解和数据。此外，我们将报告生物性别作为混杂因素的可能性以及DEX下TMS-EEG的可行性。
