Remimazolam vs. Propofol: Impact on Postoperative Delirium in Neurosurgical Patients

The occurrence of postoperative delirium, defined as at least one positive assessment during the postoperative period. Delirium will be assessed twice a day using confusion assessment method for the intensive care unit (CAM-ICU) and 3-minute diagnostic assessment for CAM-defined delirium (3D-CAM).

These are binary diagnostic instruments (delirium present vs absent), not scored scales.

Duration is quantified as the cumulative number of positive CAM-ICU or 3D-CAM assessments (protocol secondary outcome: number of positive delirium assessment) collected twice daily.

Hypoactive/hyperactive/mixed

Severity of postoperative delirium will be assessed twice a day using DRS-R-98 (delirium rating scale-revised-98); total score range 0-46; higher scores = more severe delirium.

Incidence of emergence agitation, defined as Richmond Agitation-Sedation Scale (RASS) ≥+1 within 30 minutes after extubation. RASS ranges from -5 to +4; higher scores indicate greater agitation. The outcome is binary (emergence agitation present vs absent).

Percentage of the patients who were not extubated in the OR and transferred to the ICU, delayed extubation (> 1 h after surgery completion)

Intraoperative awareness will be assessed using Modified Brice questionnaire; binary outcome, not a scored scale.

Undesirable movement of patient during surgery

bradycardia with the use of chronotropic agent, laryngeal spasm, bronchospasm, allergic reaction, arrhythmia, cardiac events (myocardial infarction, vasospasm, or cardiac arrest), or massive bleeding

Intraoperative hypotension, quantified as the area under the mean arterial pressure threshold of 65 mm Hg. (Unit: mm Hg·min)

Quality of Recovery-15 (QoR-15); score range 0-150; higher = better recovery.

assessed by Clavien-Dindo classification Data are presented as the proportion of patients with 1 or more events (edema, vasospasm, rebleeding, seizures, and/or ischemia, etc.)

days

days

the incidence of postoperative falls and associated injury (presence of fracture)

Changes in cognition assessed by Montreal Cognitive Assessment (MoCA) at baseline and postoperative day 7 (or discharge, whichever comes first); range 0-30; higher = better cognition. And by telephone-MoCA (T-MoCA) at 3 months;range 0-22; higher = better cognition.

assessed using Barthel activity of daily living (ADL) index

; score range 0-20; higher = greater independence.

PONV sub-study is a pre-planned non-inferiority sub-study for this main trial. Number (percentage) of participants with nausea and/or vomiting, assessed in participants enrolled in the PONV sub-study.

Severity of postoperative nausea and vomiting, assessed using the PONV Intensity Scale in participants enrolled in the PONV sub-study. Higher scores indicate more severe PONV.

Number (percentage) of participants who received rescue anti-emetic medication in the PONV sub-study.

Subgroup analysis (age, sex, surgery type, preoperative cognitive impairment, ASA physical status, duration of anesthesia, alcohol abuse, or chronic benzodiazepine use)

Relative spectral power in the alpha, beta, delta, and theta frequency bands, derived from intraoperative electroencephalography (EEG).

Phase-amplitude coupling between EEG frequency bands, derived from intraoperative EEG.