Moderate-to-severe acute postsurgical pain after spinal surgery can slow recovery. A combination of esketamine and pregabalin reduced the incidence of such pain from 60.5% to 27.3% in the first 48 hours after surgery, based on a randomized trial of 90 patients undergoing resection of spinal neoplasms. The odds ratio was 0.25, indicating a substantial benefit. However, mild dissociative symptoms occurred in 18.2% of the combination group versus none in the control group, suggesting the analgesic strategy carries this risk.
Among patients undergoing major surgery who had moderate-to-severe depressive symptoms before the operation, a single intraoperative dose of esketamine led to a higher rate of symptom remission three days after surgery compared with a placebo. In a randomized, double-blind trial of 435 patients, 28.3% in the esketamine group achieved remission versus 11.3% in the placebo group. Acute pain rates did not differ between groups. Esketamine treatment requires monitoring for possible dissociative side effects, and its clinical use for depressive symptoms should weigh benefits against risks.
In patients with prolonged disorders of consciousness, a one-hour intravenous infusion of esketamine (0.3 mg/kg/h) altered brain activity as measured by electroencephalography. The drug suppressed delta wave power while increasing beta and gamma wave power across the whole brain, and increased alpha wave power specifically in patients diagnosed as vegetative state/unresponsive wakefulness syndrome. Signal complexity, measured by Lempel-Ziv complexity, increased in the parietal and occipital brain regions. In minimally conscious patients, this complexity increase persisted for 30 minutes after the infusion stopped, while changes were transient in vegetative state patients. However, these neurophysiological changes were not accompanied by any improvements in behavioral responsiveness as assessed by the Coma Recovery Scale-Revised.
Consciousness is linked to how neural activity shifts along a unimodal-transmodal cortical axis, a simple signature that is abnormally elevated under psychedelics and in psychosis. This hierarchical dynamic reflects changes in global brain integration and connectome diversity. Quasi-periodic patterns show hierarchical heterogeneity as spatiotemporally propagating waves tied to arousal, a pattern also seen in macaques. The spatial distribution of the principal cortical gradient aligns with genetic transcription of the histaminergic system and functional connectome mapping of the tuberomammillary nucleus, which promotes wakefulness. Combining behavioral, neuroimaging, electrophysiological, and transcriptomic evidence, the authors propose that global consciousness is supported by efficient hierarchical processing along a low-dimensional macroscale gradient.