Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Br J Anaesth. 2021 Jan;126(1):265-278. doi: 10.1016/j.bja.2020.09.022. Epub 2020 Oct 17.
Anaesthetic induction occurs at higher plasma drug concentrations than emergence in animal studies. Some studies find evidence for such anaesthetic hysteresis in humans, whereas others do not. Traditional thinking attributes hysteresis to drug equilibration between plasma and the effect site. Indeed, a key difference between human studies showing anaesthetic hysteresis and those that do not is in how effect-site equilibration was modelled. However, the effect-site is a theoretical compartment in which drug concentration cannot be measured experimentally. Thus, it is not clear whether drug equilibration models with experimentally intractable compartments are sufficiently constrained to unequivocally establish evidence for the presence or absence of anaesthetic hysteresis.
We constructed several models. One lacked hysteresis beyond effect-site equilibration. In another, neuronal dynamics contributed to hysteresis. We attempted to distinguish between these two systems using drug equilibration models.
Our modelling studies showed that one can always construct an effect-site equilibration model such that hysteresis collapses. So long as the concentration in the effect-site cannot be measured directly, the correct effect-site equilibration model and the one that erroneously collapses hysteresis are experimentally indistinguishable. We also found that hysteresis can naturally arise even in a simple network of neurones independently of drug equilibration.
Effect-site equilibration models can readily collapse hysteresis. However, this does not imply that hysteresis is solely attributable to the kinetics of drug equilibration.
在动物研究中，麻醉诱导发生在比苏醒更高的血浆药物浓度下。一些研究在人类中发现了这种麻醉滞后的证据，而另一些则没有。传统思维将滞后归因于血浆和效应部位之间的药物平衡。事实上，在显示麻醉滞后和没有麻醉滞后的人类研究之间的一个关键区别在于如何对效应部位平衡进行建模。然而，效应部位是一个理论上的隔室，在这个隔室中药物浓度不能通过实验来测量。因此，目前尚不清楚是否可以用具有实验性难以处理的隔室的药物平衡模型来明确地建立麻醉滞后是否存在的证据。
我们构建了几种模型。一种模型在效应部位平衡之外没有滞后。另一种模型中，神经元动力学导致了滞后。我们试图使用药物平衡模型来区分这两种系统。
我们的建模研究表明，人们总是可以构建一个不存在滞后的效应部位平衡模型。只要不能直接测量效应部位的浓度，那么正确的效应部位平衡模型和错误地使滞后崩溃的模型在实验上是无法区分的。我们还发现，即使在没有药物平衡的简单神经元网络中，滞后也可以自然出现。
效应部位平衡模型可以很容易地使滞后崩溃。然而，这并不意味着滞后仅仅是由于药物平衡的动力学所致。
