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.
The anesthetic, analgesic, and antidepressant drug ketamine produces dissociation with symptoms of psychosis and anxiety, an effect attributed to neuronal nitric oxide depletion following N-methyl-d-aspartate blockade. There is evidence that dissociation induced by racemic ketamine, containing both ketamine enantiomers (S- and R-ketamine) but not esketamine (the S-isomer) is inhibited by nitric oxide (NO) donor sodium nitroprusside (SNP). We tested whether a similar intervention would reduce racemic and esketamine-induced analgesia in a randomized double-blind placebo-controlled trial. Seventeen healthy volunteers were treated with 0.5 μg.kg-1.