Ketamine and the paradox of anaesthetic state transitions

Administration of subanaesthetic doses of ketamine during isoflurane anaesthesia has been shown in animals to deepen the anaesthetised state, while accelerating emergence. Duan and colleagues have now shown that the addition of subanaesthetic doses of esketamine to isoflurane has a similar effect of increasing the burst suppression ratio, while accelerating emergence. Using c-Fos expression and fibre photometry, they show that esketamine activates glutamatergic neurones in the paraventricular nucleus of the thalamus, a structure that regulates wakefulness. Chemogenetic inhibition of these neurones attenuates the arousal-promoting effects, suggesting a causal role of the paraventricular nucleus of the thalamus in esketamine-mediated acceleration of recovery from anaesthesia.