Background:: A medically induced coma is an anesthetic state of profound brain inactivation created to treat status epilepticus and to provide cerebral protection after traumatic brain injuries. The authors hypothesized that a closed-loop anesthetic delivery system could automatically and precisely control the electroencephalogram state of burst suppression and efficiently maintain a medically induced coma.Methods:: In six rats, the authors implemented a closed-loop anesthetic delivery system for propofol consisting of: a computer-controlled pump infusion, a two-compartment pharmacokinetics model defining propofol’s electroencephalogram effects, the burst-suppression probability algorithm to compute in real time from the electroencephalogram the brain’s burst-suppression state, an online parameter-estimation procedure and a proportional-integral controller. In the control experiment each rat was randomly assigned to one of the six burst-suppression probability target trajectories constructed by permuting the burst-suppression probability levels of 0.4, 0.65, and 0.9 with linear transitions between levels.Results:: In each animal the controller maintained approximately 60 min of tight, real-time control of burst suppression by tracking each burst-suppression probability target level for 15 min and two between-level transitions for 5–10 min. The posterior probability that the closed-loop anesthetic delivery system was reliable across all levels was 0.94 (95% CI, 0.77–1.00; n = 18) and that the system was accurate across all levels was 1.00 (95% CI, 0.84–1.00; n = 18).Conclusion:: The findings of this study establish the feasibility of using a closed-loop anesthetic delivery systems to achieve in real time reliable and accurate control of burst suppression in rodents and suggest a paradigm to precisely control medically induced coma in patients.A closed-loop anesthesia delivery system using a computer-controlled infusion of propofol can achieve a reliable and accurate real-time control of burst suppression in rats.
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机译：背景：医学上引起的昏迷是一种严重的大脑失活的麻醉状态，可用于治疗癫痫持续状态并在脑外伤后提供脑保护。作者假设闭环麻醉剂输送系统可自动精确控制猝发抑制的脑电图状态并有效维持医学上引起的昏迷。方法：：在六只大鼠中，作者实施了异丙酚麻醉剂的闭环麻醉剂输送系统包括：计算机控制的输液泵，定义丙泊酚的脑电图效应的两室药代动力学模型，可从脑电图实时计算大脑的突发抑制状态的突发抑制概率算法，在线参数估计程序和比例-集成控制器。在对照实验中，每只大鼠被随机分配到六个爆破抑制目标目标轨迹之一，该目标轨迹是通过将爆破抑制概率水平分别在0.4、0.65和0.9之间进行线性转换而构造的。结果：:在每只动物中，控制器通过跟踪每个突发抑制概率目标级别15分钟和两次级别间过渡5-10分钟，可以保持大约60分钟的紧密实时的突发抑制控制。闭环麻醉剂输送系统在所有水平上可靠的后验概率为0.94（95％CI，0.77–1.00; n = 18），而在所有水平上该系统准确的后验概率为1.00（95％CI，0.84–1.00） ; n = 18）。结论：：本研究的发现建立了使用闭环麻醉剂输送系统实时，可靠，准确地控制啮齿类动物猝发抑制的可行性，并提出了一种精确控制药物引起的昏迷的范例使用计算机控制的异丙酚输注的闭环麻醉输送系统可以实现对大鼠猝发抑制的可靠，准确的实时控制。
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