Esketamine Preserves Network Connectivity and Promotes Recovery in Consciousness Disorders

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.

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.

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).

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.