Ciprofol and Remimazolam for Intraoperative Neurophysiological Monitoring During Spine Surgery

MEP and SEP monitoring are important components of intraoperative neurophysiological monitoring during complex spine surgery. However, evoked potential amplitudes and latencies are influenced not only by neurological injury but also by anesthetic depth, hypnotic agents, opioids, blood pressure, temperature, carbon dioxide, residual neuromuscular blockade, stimulation parameters, patient positioning, and surgical stage. Total intravenous anesthesia is therefore commonly preferred when reliable MEP monitoring is required. Ciprofol is a propofol analogue acting mainly on GABAA receptors and may provide sedation or anesthesia with less circulatory depression in some settings. Remimazolam is a short-acting benzodiazepine metabolized by tissue esterases and can be antagonized by flumazenil. Existing studies have compared each drug with propofol or reported successful MEP monitoring under remimazolam, but there is no direct randomized crossover comparison of ciprofol and remimazolam during spine surgery requiring MEP and SEP monitoring. In this trial, each participant will serve as his or her own control. Participants will be randomized in a 1:1 ratio to one of two sequences: ciprofol followed by remimazolam or remimazolam followed by ciprofol. Both study periods will be conducted under remifentanil-based analgesia and similar targets for anesthetic depth, hemodynamics, ventilation, temperature, and neuromuscular recovery. MEP and SEP recordings will be obtained during stable intraoperative windows before and after drug transition. The study aims to determine whether one agent provides more favorable neurophysiological monitoring signal quality while maintaining acceptable hemodynamic stability and surgical conditions.

Inclusion criteria

• Age 18 to 75 years.
• Scheduled to undergo elective spine surgery.
• Planned intraoperative monitoring with MEP and SEP/SSEP.
• Expected surgical duration sufficient to complete two study drug periods and intraoperative monitoring windows, preferably at least 3.5 to 4 hours.
• American Society of Anesthesiologists physical status I to III.
• Able to provide written informed consent, or consent provided by a legally authorized representative where applicable.

Exclusion criteria

• Known allergy or contraindication to ciprofol, remimazolam, benzodiazepines, propofol-related formulations, opioids, or relevant excipients.
• Severe preoperative motor or sensory deficit preventing interpretable target MEP or SEP baseline recordings.
• Implanted cardiac pacemaker, skull defect, or other condition considered unsuitable for transcranial electrical stimulation.
• Severe neuromuscular disease, poorly controlled epilepsy, severe cognitive impairment, or inability to complete postoperative neurological assessment.
• Severe hepatic or renal dysfunction, severe hemodynamic instability, shock, or requirement for high-dose vasoactive medications before enrollment.
• Long-term benzodiazepine, sedative-hypnotic, antiepileptic drug use, or drug/alcohol dependence that may substantially alter anesthetic response.
• Expected need for continuous deep neuromuscular blockade during surgery, preventing valid MEP monitoring.
• Any other condition judged by the investigators to make participation unsuitable or unsafe.