Breathe-squeeze: pharmacodynamics of a stimulus-free behavioural paradigm to track conscious states during sedation*
Breathe-squeeze: pharmacodynamics of a stimulus-free behavioural paradigm to track conscious states during sedation*
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DOI：
10.1016/j.bja.2023.01.021
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发表时间：
2023-04-10
影响因子：
9.8
通讯作者：
Palanca, Ben Julian A.
中科院分区：
文献类型：
--
作者：
Guay, Christian S.;Hight, Darren;Palanca, Ben Julian A.
背景：意识状态通常通过对听觉任务和有害刺激的反应来推断。我们报告了使用一种无刺激的行为范式来追踪右美托咪定镇静期间反应性的状态转变。我们假设，与反应恢复（ROR）相比，在反应消失（LOR）时估计的右美托咪定效应室（Ce）浓度会更高，并且两者都会低于使用基于刺激的评估的类似研究。方法：对右美托咪定镇静期间的闭环声学刺激数据进行二次分析。14名健康志愿者被要求在吸气时握住测力计进行呼吸 - 挤压任务，并在呼气时松开。LOR定义为5次吸气时无伴随的挤压；ROR定义为5次吸气伴随挤压的恢复。使用64通道脑电图监测大脑状态。右美托咪定作为目标控制输注给药，根据药代动力学模型估计Ce。结果：与我们的假设相反，LOR时估计的右美托咪定平均Ce（0.92纳克/毫升；95%置信区间：0.69 - 1.15）低于ROR时（1.43纳克/毫升；95%置信区间：1.27 - 1.58）（配对t检验；P = 0.002）。LOR的特征是0.5 - 8赫兹频段的额 - 枕脑电图功率逐渐增加，以及枕部α（8 - 12赫兹）和整体β（16 - 30赫兹）功率丧失。这些脑电图变化在ROR时恢复。结论：呼吸 - 挤压任务可以在无外部刺激的情况下有效追踪镇静期间反应性的变化，并且可能比基于刺激的任务对状态变化更敏感。当不希望干扰大脑状态时应考虑使用该任务。临床试验注册：NCT04206059
Background: 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 dexmedeto-midine 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. Methods: 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. Results: Counter to our hypothesis, mean estimated dexmedetomidine Ce was lower at LOR (0.92 ng ml -1; 95% confi-dence interval: 0.69-1.15) than at ROR (1.43 ng ml -1; 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. Conclusions: 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. Clinical trial registration: NCT04206059.