Closed-loop control of anesthetic state in nonhuman primates.

Closed-loop control of anesthetic state in nonhuman primates.
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非人灵长类动物麻醉状态的闭环控制。

DOI:
10.1093/pnasnexus/pgad293
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发表时间:
2023-10
期刊:
PNAS NEXUS
影响因子:
--
通讯作者:
Brown, Emery N.
Brown, Emery N.
中科院分区:
其他
文献类型:
--
作者:
Chakravarty, Sourish;Donoghue, Jacob;Waite, Ayan S.;Mahnke, Meredith;Garwood, Indie C.;Gallo, Sebastian;Miller, Earl K.;Brown, Emery N.

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对人类志愿者和手术患者的研究表明,利用实时脑电图处理能够可靠地追踪全身麻醉下的无意识状态。因此,一个能精确维持特定无意识水平的闭环麻醉给药(CLAD)系统是可行的,并且将极大地有助于术中患者的管理。美国食品药品监督管理局尚未批准任何用于人类的CLAD系统,部分原因是缺乏在合适动物模型中的测试。为了解决这一关键障碍,我们实施了一个利用麻醉剂丙泊酚控制无意识水平的非人灵长类动物(NHP)CLAD系统。该系统的关键组件包括局部场电位(LFP)记录系统、丙泊酚药代动力学和药效学模型、控制变量(20到30赫兹之间的LFP功率)、一个可编程输液系统以及一个线性二次积分控制器。我们的CLAD系统在两只非人灵长类动物身上进行的9次实验中,沿着两条不同的125分钟动态目标轨迹,在18小时45分钟内准确地控制了无意识水平。系统性能指标与之前CLAD报告中的相当或更优。我们证明了一个非人灵长类动物CLAD系统能够可靠且准确地实时控制由麻醉维持的无意识状态。我们的研究结果为在人体测试之前CLAD系统的设计和测试确立了关键步骤。
Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of unconsciousness is feasible and would greatly aid intraoperative patient management. The US Federal Drug Administration has approved no CLAD system for human use due partly to a lack of testing in appropriate animal models. To address this key roadblock, we implement a nonhuman primate (NHP) CLAD system that controls the level of unconsciousness using the anesthetic propofol. The key system components are a local field potential (LFP) recording system; propofol pharmacokinetics and pharmacodynamic models; the control variable (LFP power between 20 and 30 Hz), a programmable infusion system and a linear quadratic integral controller. Our CLAD system accurately controlled the level of unconsciousness along two different 125-min dynamic target trajectories for 18 h and 45 min in nine experiments in two NHPs. System performance measures were comparable or superior to those in previous CLAD reports. We demonstrate that an NHP CLAD system can reliably and accurately control in real-time unconsciousness maintained by anesthesia. Our findings establish critical steps for CLAD systems’ design and testing prior to human testing.
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