University of Groningen, University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands.
University of Groningen, University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands; Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
Br J Anaesth. 2018 Mar;120(3):525-536. doi: 10.1016/j.bja.2017.11.072. Epub 2017 Dec 1.
Neural inertia is defined as the tendency of the central nervous system to resist transitions between arousal states. This phenomenon has been observed in mice and Drosophila anaesthetized with volatile anaesthetics: the effect-site concentration required to induce anaesthesia in 50% of the population (C) was significantly higher than the effect-site concentration for 50% of the population to recover from anaesthesia. We evaluated this phenomenon in humans using propofol or sevoflurane (both with or without remifentanil) as anaesthetic agents.
Thirty-six healthy volunteers received four sessions of anaesthesia with different drug combinations in a step-up/step-down design. Propofol or sevoflurane was administered with or without remifentanil. Serum concentrations of propofol and remifentanil were measured from arterial blood samples. Loss and return of responsiveness (LOR-ROR), response to pain (PAIN), Patient State Index (PSI) and spectral edge frequency (SEF) were modeled with NONMEM®.
For propofol, the C for induction and recovery of anaesthesia was not significantly different across the different endpoints. For sevoflurane, for all endpoints except SEF, significant differences were found. For some endpoints (LOR and PAIN) the difference was significant only when sevoflurane was combined with remifentanil.
Our results nuance earlier findings with volatile anaesthetics in mice and Drosophila. Methodological aspects of the study, such as the measured endpoint, influence the detection of neural inertia. A more thorough definition of neural inertia, with a robust methodological framework for clinical studies is required to advance our knowledge of this phenomenon.
NCT 02043938.
神经惯性是指中枢神经系统抵抗从一种觉醒状态转变为另一种觉醒状态的趋势。这种现象在使用挥发性麻醉剂麻醉的小鼠和果蝇中已经观察到：诱导麻醉 50%人群所需的效应部位浓度（C）明显高于麻醉 50%人群恢复麻醉所需的效应部位浓度。我们使用丙泊酚或七氟醚（均合用或不合用瑞芬太尼）作为麻醉剂在人类中评估了这种现象。
36 名健康志愿者采用递增/递减设计，接受了四种不同药物组合的麻醉。给予丙泊酚或七氟醚合用或不合用瑞芬太尼。从动脉血样中测量丙泊酚和瑞芬太尼的血清浓度。用 NONMEM®对意识丧失和恢复（LOR-ROR）、疼痛反应（PAIN）、患者状态指数（PSI）和频谱边缘频率（SEF）进行建模。
对于丙泊酚，麻醉诱导和恢复的 C 在不同的终点之间没有显著差异。对于七氟醚，除 SEF 外，所有终点均存在显著差异。对于某些终点（LOR 和 PAIN），只有当七氟醚与瑞芬太尼合用时，差异才具有统计学意义。
我们的结果细微地改变了以前在小鼠和果蝇中挥发性麻醉剂的发现。研究的方法学方面，如测量终点，影响了对神经惯性的检测。需要更全面地定义神经惯性，并建立用于临床研究的稳健方法学框架，以推进我们对这一现象的认识。
NCT 02043938。
