Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Anaesthesiology & Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Br J Anaesth. 2023 May;130(5):557-566. doi: 10.1016/j.bja.2023.01.021. Epub 2023 Mar 24.
Conscious states are typically inferred through responses to auditory tasks and noxious stimulation. We report the use of a stimulus-free behavioural paradigm to track state transitions in responsiveness during dexmedetomidine sedation. We hypothesised that estimated dexmedetomidine effect-site (Ce) concentrations would be higher at loss of responsiveness (LOR) compared with return of responsiveness (ROR), and both would be lower than comparable studies that used stimulus-based assessments.
Closed-Loop Acoustic Stimulation during Sedation with Dexmedetomidine data were analysed for secondary analysis. Fourteen healthy volunteers were asked to perform the breathe-squeeze task of gripping a dynamometer when inspiring and releasing it when expiring. LOR was defined as five inspirations without accompanied squeezes; ROR was defined as the return of five inspirations accompanied by squeezes. Brain states were monitored using 64-channel EEG. Dexmedetomidine was administered as a target-controlled infusion, with Ce estimated from a pharmacokinetic model.
Counter to our hypothesis, mean estimated dexmedetomidine Ce was lower at LOR (0.92 ng ml; 95% confidence interval: 0.69-1.15) than at ROR (1.43 ng ml; 95% confidence interval: 1.27-1.58) (paired t-test; P=0.002). LOR was characterised by progressively increasing fronto-occipital EEG power in the 0.5-8 Hz band and loss of occipital alpha (8-12 Hz) and global beta (16-30 Hz) power. These EEG changes reverted at ROR.
The breathe-squeeze task can effectively track changes in responsiveness during sedation without external stimuli and might be more sensitive to state changes than stimulus-based tasks. It should be considered when perturbation of brain states is undesirable.
NCT04206059.
意识状态通常通过对听觉任务和有害刺激的反应来推断。我们报告了一种无刺激行为范式的使用，以跟踪右美托咪定镇静期间反应性的状态转变。我们假设，与恢复反应性（ROR）相比，在失去反应性（LOR）时，估计的右美托咪定效应部位（Ce）浓度会更高，并且两者都将低于使用基于刺激的评估的可比研究。
对 Dexmedetomidine 镇静期间闭环声刺激数据进行了二次分析。14 名健康志愿者被要求在吸气时执行呼吸-挤压任务，即紧握测力计，在呼气时松开。LOR 定义为五次吸气无伴随挤压；ROR 定义为五次吸气伴随挤压的恢复。使用 64 通道 EEG 监测大脑状态。右美托咪定作为靶控输注给药，从药代动力学模型估计 Ce。
与我们的假设相反，在 LOR（0.92ng/ml；95%置信区间：0.69-1.15）时，估计的右美托咪定 Ce 的平均值低于 ROR（1.43ng/ml；95%置信区间：1.27-1.58）（配对 t 检验；P=0.002）。LOR 的特征是在 0.5-8 Hz 频段中额枕 EEG 功率逐渐增加，以及枕 alpha（8-12 Hz）和全局 beta（16-30 Hz）功率的丧失。这些 EEG 变化在 ROR 时恢复。
呼吸-挤压任务可以在没有外部刺激的情况下有效地跟踪镇静期间反应性的变化，并且可能比基于刺激的任务更敏感地反映状态变化。在不希望大脑状态受到干扰的情况下，应考虑使用该任务。
NCT04206059。
