BACKGROUND The acute hypoxic ventilatory response is a critical chemoreflex originating at the carotid bodies. This study investigates the impact of low-dose i.v. esketamine on the ventilatory response to 20 min of isocapnic hypoxia to test the hypothesis that esketamine does not affect hypoxic ventilation. METHODS In this open-label study, 18 healthy subjects received a 3-h escalating i.v. infusion of esketamine, totalling 1.0 mg kg-1. Before the esketamine infusion (control condition) and during the last 30 min of infusion, the ventilatory response to 20 min of isocapnic hypoxia (oxygen saturation ∼80%) was measured. We assessed the increase in ventilation from baseline to its peak during the first 5 min of isocapnic hypoxia (hypoxic ventilatory response) and the increase in ventilation from baseline to 20 min of isocapnic hypoxia (sustained hypoxia). Haemodynamics and acute brain function were also measured. RESULTS Independent of hypoxia, a small excitatory effect of ketamine on isocapnic ventilation was observed: the mean increase in ventilation (95% confidence interval) was 3.1 (2.4-3.7) L min-1 (P<0.0001). Esketamine had no effect on the isocapnic ventilatory response to acute and sustained hypoxia but increased MAP (+10 mm Hg) and heart rate (+10 beats min-1), similarly during normoxia and hypoxia. Esketamine increased anxiety and alertness and affected external perception. CONCLUSIONS I.V. esketamine up to 1 mg kg-1 does not affect the ventilatory response to hypoxia, but affects haemodynamics and acute brain function. Increases in anxiety and alertness could be a cause of the sustained ventilatory response to hypoxia during esketamine infusion. CLINICAL TRIAL REGISTRATION The trial was registered at the ISRCTN registry on June 27, 2023 under identifier ISRCTN 42617929 (https://www.isrctn.com/ISRCTN42617929).

中文翻译：

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艾氯胺酮对健康志愿者低氧通气反应、血流动力学和脑功能的急性影响。


背景 急性低氧通气反应是起源于颈动脉体的关键化学反射。本研究调查了低剂量静脉注射艾氯胺酮对 20 分钟等碳酸血症缺氧通气反应的影响，以检验艾氯胺酮不影响低氧通气的假设。方法 在这项开放标签研究中，18 名健康受试者接受了 3 小时递增静脉注射艾氯胺酮，总计 1.0 mg kg-1。在艾氯胺酮输注前 （对照条件） 和输注的最后 30 分钟期间，测量对 20 分钟等碳酸血症缺氧 （氧饱和度 ∼80%） 的通气反应。我们评估了等碳酸血症缺氧 （缺氧通气反应） 前 5 分钟内通气量从基线到峰值的增加量，以及从基线到等碳酸血症缺氧 （持续缺氧） 20 分钟通气量的增加。还测量了血流动力学和急性脑功能。结果 与缺氧无关，观察到氯胺酮对等碳酸血症通气的小型兴奋作用：通气平均增加 （95% 置信区间） 为 3.1 （2.4-3.7） L min-1 （P<0.0001）。艾氯胺酮对急性和持续缺氧的等碳酸血症通气反应没有影响，但会增加 MAP （+10 mm Hg） 和心率（+10 次 min-1），同样在常氧和缺氧期间。艾氯胺酮增加了焦虑和警觉性，并影响了外部感知。结论 静脉注射艾氯胺酮高达 1 mg kg-1 不会影响对缺氧的通气反应，但会影响血流动力学和急性脑功能。焦虑和警觉性的增加可能是艾氯胺酮输注期间对缺氧持续通气反应的一个原因。 临床试验注册该试验于 2023 年 6 月 27 日在 ISRCTN 注册处注册，标识符为 ISRCTN 42617929 （https://www.isrctn.com/ISRCTN42617929）。