van den Elsen M, Sarton E, Teppema L, Berkenbosch A, Dahan A
Department of Anesthesiology, Leiden University Medical Centre, The Netherlands.
Br J Anaesth. 1998 Feb;80(2):174-82. doi: 10.1093/bja/80.2.174.
To assess the effects and site of action of a sub-anaesthetic concentration of isoflurane, desflurane and sevoflurane (0.1 minimum alveolar concentration (MAC)) on respiratory control, we measured the ventilatory response to square wave changes in PE1CO2 against a background of normoxia. Using the computer steered "end-tidal forcing system", 2 min of steady state ventilation were followed by a step increase in PE1CO2 (1-1.5 kPa). This level was maintained for 8 min, followed by a step decrease to the original value for another 8 min. Each hypercapnic response was separated into a fast, peripheral component and a slow, central component, characterized by a time constant, carbon dioxide sensitivity, time delay and off-set. We studied 25 healthy volunteers; they performed 2-3 studies without and 2-3 studies during inhalation of the anaesthetic agent. Level of sedation was scored using a subjective seven-point scale from 0 (= alert and awake) to 6 (unrousable). In the isoflurane (16 subjects, 33 control, 37 drug studies) and sevoflurane (15 subjects, 40 control, 41 drug studies) studies, peripheral carbon dioxide sensitivity was reduced by approximately 45% and approximately 27% (ANOVA, P < 0.05 vs control), respectively, without affecting central carbon dioxide sensitivity or apnoeic threshold. In the desflurane study (16 subjects, 36 control, 37 drug studies), no significant effect was observed for any of the variables measured. A significant relation was observed between sedation score and change from control in central carbon dioxide sensitivities in the isoflurane and desflurane studies and in the change in the ratio peripheral carbon dioxide sensitivity over total carbon dioxide sensitivity in the sevoflurane studies. At the highest level of sedation observed (score 3-arousal state comparable with "light sleep"--in three subjects) these latter variables differed significantly from those in the other observed sedation levels (scores 1 and 2-a state of drowsiness). We conclude that 0.1 MAC of isoflurane and sevoflurane depressed the peripheral chemoreflex loop, without affecting the central chemoreflex loop. Desflurane at the same MAC showed no effect on peripheral and central carbon dioxide sensitivity. When the level of sedation was considered, our data suggested that at levels of sedation comparable with sleep, a depressive effect of all three anaesthetics was observed on the central chemoreflex loop.
为评估亚麻醉浓度的异氟烷、地氟烷和七氟烷（0.1最低肺泡浓度（MAC））对呼吸控制的作用及作用部位，我们在常氧背景下测量了对呼气末二氧化碳（PE1CO2）方波变化的通气反应。使用计算机控制的“呼气末强制系统”，先进行2分钟的稳态通气，然后PE1CO2逐步升高（1 - 1.5 kPa）。该水平维持8分钟，随后再逐步降至初始值并维持8分钟。每个高碳酸血症反应被分为快速外周成分和缓慢中枢成分，其特征为时间常数、二氧化碳敏感性、时间延迟和偏移。我们研究了25名健康志愿者；他们在未吸入麻醉剂时进行了2 - 3次研究，在吸入麻醉剂期间也进行了2 - 3次研究。使用从0（=警觉清醒）到6（无法唤醒）的主观七点量表对镇静水平进行评分。在异氟烷研究（16名受试者，33次对照，37次药物研究）和七氟烷研究（15名受试者，40次对照，41次药物研究）中，外周二氧化碳敏感性分别降低了约45%和约27%（方差分析，与对照相比P < 0.05），而不影响中枢二氧化碳敏感性或呼吸暂停阈值。在地氟烷研究（16名受试者，36次对照，37次药物研究）中，未观察到所测任何变量有显著影响。在异氟烷和地氟烷研究中，观察到镇静评分与中枢二氧化碳敏感性相对于对照的变化之间存在显著关系，在七氟烷研究中，观察到外周二氧化碳敏感性与总二氧化碳敏感性之比的变化与镇静评分之间存在显著关系。在观察到的最高镇静水平（三名受试者评分为3 - 唤醒状态相当于“浅睡眠”）下，这些后述变量与其他观察到的镇静水平（评分1和2 - 嗜睡状态）下的变量有显著差异。我们得出结论，0.1 MAC的异氟烷和七氟烷抑制外周化学反射环，而不影响中枢化学反射环。相同MAC的地氟烷对外周和中枢二氧化碳敏感性无影响。当考虑镇静水平时，我们的数据表明，在与睡眠相当的镇静水平下，观察到所有三种麻醉剂对中枢化学反射环均有抑制作用。
