van den Elsen M, Dahan A, DeGoede J, Berkenbosch A, van Kleef J
Department of Anesthesiology, University Hospital Leiden, The Netherlands.
Anesthesiology. 1995 Sep;83(3):478-90. doi: 10.1097/00000542-199509000-00006.
The purpose of this study was to quantify in humans the effects of subanesthetic isoflurane on the ventilatory control system, in particular on the peripheral chemoreflex loop. Therefore we studied the dynamic ventilatory response to carbon dioxide, the effect of isoflurane wash-in upon sustained hypoxic steady-state ventilation, and the ventilatory response at the onset of 20 min of isocapnic hypoxia.
Study 1: Square-wave changes in end-tidal carbon dioxide tension (7.5-11.5 mmHg) were performed in eight healthy volunteers at 0 and 0.1 minimum alveolar concentration (MAC) isoflurane. 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 (apneic threshold). Study 2: The ventilatory changes due to the wash-in of 0.1 MAC isoflurane, 15 min after the induction of isocapnic hypoxia, were studied in 11 healthy volunteers. Study 3: The ventilatory responses to a step decrease in end-tidal oxygen (end-tidal oxygen tension from 110 to 44 mmHg within 3-4 breaths; duration of hypoxia 20 min) were assessed in eight healthy volunteers at 0, 0.1, and 0.2 MAC isoflurane.
Values are reported as means +/- SF. Study 1: The peripheral carbon dioxide sensitivities averaged 0.50 +/- 0.08 (control) and 0.28 +/- 0.05 l.min-1.mmHg-1 (isoflurane; P < 0.01). The central carbon dioxide sensitivities (control 1.20 +/- 0.12 vs. isoflurane 1.04 +/- 0.11 l.min-1.mmHg-1) and off-sets (control 36.0 +/- 0.1 mmHg vs. isoflurane 34.5 +/- 0.2 mmHg) did not differ between treatments. Study 2: Within 30 s of exposure to 0.1 MAC isoflurane, ventilation decreased significantly, from 17.7 +/- 1.6 (hypoxia, awake) to 15.0 +/- 1.5 l.min-1 (hypoxia, isoflurane). Study 3: At the initiation of hypoxia ventilation increased by 7.7 +/- 1.4 (control), 4.1 +/- 0.8 (0.1 MAC; P < 0.05 vs. control), and 2.8 +/- 0.6 (0.2 MAC; P < 0.05 vs. control) l.min-1. The subsequent ventilatory decrease averaged 4.9 +/- 0.8 (control), 3.4 +/- 0.5 (0.1 MAC; difference not statistically significant), and 2.0 +/- 0.4 (0.2 MAC; P < 0.05 vs. control) l.min-1. There was a good correlation between the acute hypoxic response and the hypoxic ventilatory decrease (r = 0.9; P < 0.001).
The results of all three studies indicate a selective and profound effect of subanesthetic isoflurane on the peripheral chemoreflex loop at the site of the peripheral chemoreceptors. We relate the reduction of the ventilatory decrease of sustained hypoxia to the decrease of the initial ventilatory response to hypoxia.
本研究旨在量化人体中亚麻醉剂量异氟烷对通气控制系统的影响，尤其是对外周化学反射环的影响。因此，我们研究了对二氧化碳的动态通气反应、异氟烷吸入对持续性低氧稳态通气的影响以及等碳酸血症性低氧20分钟开始时的通气反应。
研究1：在8名健康志愿者中，于0和0.1最低肺泡浓度（MAC）异氟烷时进行呼气末二氧化碳分压的方波变化（7.5 - 11.5 mmHg）。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（呼吸暂停阈值）。研究2：在11名健康志愿者中，研究了等碳酸血症性低氧诱导15分钟后吸入0.1 MAC异氟烷引起的通气变化。研究3：在8名健康志愿者中，评估了在0、0.1和0.2 MAC异氟烷时对呼气末氧分压的阶跃下降（呼气末氧分压在3 - 4次呼吸内从110降至44 mmHg；低氧持续时间20分钟）的通气反应。
数值以均值±标准误报告。研究1：外周二氧化碳敏感性平均为0.50±0.08（对照）和0.28±0.05 l·min⁻¹·mmHg⁻¹（异氟烷；P < 0.01）。中枢二氧化碳敏感性（对照1.20±0.12与异氟烷1.04±0.11 l·min⁻¹·mmHg⁻¹）和偏移（对照36.0±0.1 mmHg与异氟烷34.5±0.2 mmHg）在各处理组间无差异。研究2：暴露于0.1 MAC异氟烷后30秒内，通气显著下降，从17.7±1.6（低氧，清醒）降至15.0±1.5 l·min⁻¹（低氧，异氟烷）。研究3：在低氧开始时，通气增加了7.7±1.4（对照）、4.1±0.8（0.1 MAC；与对照相比P < 0.05）和2.8±0.6（0.2 MAC；与对照相比P < 0.05）l·min⁻¹。随后的通气下降平均为4.9±0.8（对照）、3.4±0.5（0.1 MAC；差异无统计学意义）和2.0±0.4（0.2 MAC；与对照相比P < 0.05）l·min⁻¹。急性低氧反应与低氧通气下降之间存在良好的相关性（r = 0.9；P < 0.001）。
所有三项研究的结果表明，亚麻醉剂量异氟烷对外周化学感受器部位的外周化学反射环有选择性且显著的影响。我们将持续性低氧时通气下降的减少与对低氧的初始通气反应的降低联系起来。
