Acute effects of esketamine on hypoxic ventilatory response, haemodynamics, and brain function in healthy volunteers.

Intravenous esketamine up to a total dose of 1 mg per kg does not impair the ventilatory response to hypoxia in healthy adults. In an open-label study of 18 subjects, esketamine increased resting ventilation by about 3.1 L per minute and raised mean arterial pressure by 10 mm Hg and heart rate by 10 beats per minute, but it did not alter the increase in breathing triggered by acute or sustained low oxygen. The drug also increased anxiety and alertness and altered external perception, which may contribute to the sustained hypoxic ventilatory response observed during infusion. These findings indicate that low-dose esketamine is safe with respect to the hypoxic chemoreflex but has cardiovascular and psychoactive effects.

Study at a glance

Abstract

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. 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. 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. 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. The trial was registered at the ISRCTN registry on June 27, 2023 under identifier ISRCTN 42617929 (https://www.isrctn.com/ISRCTN42617929).