Esketamine Preserves Network Connectivity and Promotes Recovery in Consciousness Disorders

Abstract

Background: Disorders of consciousness (DoC) present significant therapeutic challenges with limited effective interventions. The choice of anesthetic agent during procedures such as spinal cord stimulation may influence long-term neurological outcomes, yet comparative evidence is scarce. This prospective, non-randomized, comparative effectiveness trial investigated the neurophysiological and clinical effects of esketamine versus propofol in patients with DoC.

Methods: In this prospective, non-randomized trial, 34 adult DoC patients undergoing spinal cord stimulator implantation were allocated to receive either esketamine (n = 17) or propofol (n = 17) as the primary anesthetic, based on clinical practice. Multimodal assessments included the Coma Recovery Scale-Revised (CRS-R) at baseline and 3-month follow-up, along with high-density electroencephalography (EEG) to analyze permutation entropy (PE) and weighted phase lag index (wPLI). Multivariable regression adjusted for key confounders.

Results: Compared to propofol, esketamine was associated with significantly faster recovery of spontaneous respiration (12.02 ± 3.88 vs. 17.42 ± 4.62 min, p = 0.005) and reduced need for intraoperative vasopressors (17.65% vs. 52.94%, p = 0.034). EEG analysis revealed that esketamine better preserved brain electrical complexity (higher permutation entropy during maintenance, p < 0.001) and maintained higher functional connectivity, particularly in the gamma band (weighted phase lag index, p = 0.054).

Conclusion: Esketamine demonstrates superior neurophysiological preservation over propofol in patients with disorders of consciousness, maintaining neural complexity and gamma-band connectivity during anesthesia. These mechanisms are associated with accelerated respiratory recovery, hemodynamic stability, and significantly improved consciousness outcomes at 3 months, supporting its potential as a neuroprotective anesthetic in this population.

Keywords: coma recovery scale–revised; disorders of consciousness; electroencephalography; esketamine; network connectivity; propofol.