Effects of remimazolam vs. propofol on plasma neurofilament light chain and postoperative delirium in frail elderly patients undergoing major non-cardiac surgery: a prospective, randomized, assessor-blinded controlled trial

BACKGROUND: The relationship between remimazolam administration and early neurological complications, particularly postoperative delirium (POD), in elderly patients undergoing major non-cardiac surgery remains unclear. Plasma neurofilament light chain (NfL) is a potential biomarker for central nervous injury. This study aims to compare the effects of remimazolam and propofol on postoperative plasma NfL concentrations and the incidence of POD in frail elderly patients undergoing major non-cardiac surgery. METHODS: This was a single-center randomized controlled trial on frail patients who underwent non-cardiac surgery. Participants were randomized to receive either Remimazolam (Group R) or Propofol (Group P) for induction and maintenance of general anesthesia, with all other anesthetic management standardized. The primary outcome was plasma NfL concentration on postoperative day 1, and the incidence of POD was assessed as a key clinical secondary endpoint. The secondary endpoint encompassed the incidence of hypotension during the anesthesia induction, as well as the time-weighted average of the area under the curve below the baseline for mean arterial pressure (AUB-MAP). RESULTS: A total of 123 patients were enrolled. No significant differences were observed in plasma NfL concentrations on postoperative day 1 between Group R and Group P (123.3[83.6-198.2] vs. 149.0[102.0-226.6], pg/ml, P = 0.186, respectively); and similarly, no differences in POD were found between Group R and Group P (6/62[9.7%] vs. 7/61[11.5%], unadjusted odds ratio 0.827, 95% CI 0.261-2.62, P = 0.746). In the secondary outcomes, the incidence of hypotension during the anesthesia induction in Group R was significantly decreased (3[4.8%] vs. 19[31.3%], P < 0.001). And the time-weighted average of AUB-MAP in Group R was higher than Group P (-21.3 ± 10.7 vs. -25.4 ± 9.6, mmHg, P = 0.03). CONCLUSIONS: In frail elderly patients undergoing major non-cardiac surgery, remimazolam group shows no significant difference from propofol in plasma NfL levels or POD incidence on the first day. Due to its advantage in maintaining hemodynamic stability, remimazolam may be a safer anesthetic option for frail patients sensitive to hemodynamic changes. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR2400093862.