Anesthesia, Intraoperative Neurophysiological Monitoring, Spine Surgery
Conditions
Keywords
Ciprofol, Remimazolam, Motor evoked potential, Somatosensory evoked potential, Intraoperative neurophysiological monitoring, Spine surgery, Total intravenous anesthesia, Crossover trial
Brief summary
Intraoperative neurophysiological monitoring, including motor evoked potentials and somatosensory evoked potentials, is commonly used during spine surgery to help detect impending neurological injury. The quality of these signals can be affected by anesthetic agents. Ciprofol and remimazolam are newer intravenous hypnotic agents that may be suitable for total intravenous anesthesia during procedures requiring neurophysiological monitoring, but direct within-patient comparisons between the two agents are lacking. This single-center, prospective, randomized, two-sequence crossover trial will compare the effects of ciprofol and remimazolam, administered with remifentanil, on intraoperative MEP and SEP signal quality during spine surgery. Eligible participants will be randomized to receive either ciprofol followed by remimazolam or remimazolam followed by ciprofol during predefined stable intraoperative monitoring windows. The primary outcome is the within-participant difference in lower-extremity MEP peak-to-peak amplitude between the ciprofol and remimazolam periods. Secondary outcomes include SEP amplitude and latency, MEP latency, warning-threshold events, hemodynamic variables, rescue medication requirements, recovery characteristics, and postoperative neurological status.
Detailed description
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.
Interventions
DRUGCiprofol
Ciprofol will be administered intravenously for induction and/or maintenance according to the institutional anesthesia protocol and product labeling. A suggested maintenance range is approximately 0.8 to 1.5 mg/kg/h, adjusted according to anesthetic depth, hemodynamics, surgical conditions, and patient safety.
DRUGRemimazolam
Remimazolam will be administered intravenously for induction and/or maintenance according to the institutional anesthesia protocol and product labeling. A suggested maintenance range is approximately 0.5 to 2 mg/kg/h or 1 to 2 mg/kg/h, adjusted according to anesthetic depth, hemodynamics, surgical conditions, body movement, and patient safety.
Sponsors
Affiliated 2 Hospital of Nantong University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Outcomes Assessor)
Masking description
The attending anesthesiologist cannot be fully masked because the study drugs require different preparation and infusion strategies. Intraoperative neurophysiological monitoring interpreters, data abstractors, and statistical analysts will be blinded to the coded drug sequence whenever feasible.
Intervention model description
Participants will be randomized in a 1:1 ratio to one of two two-period sequences. In the CR sequence, ciprofol will be used during the first stable intraoperative monitoring period and then switched to remimazolam for the second period. In the RC sequence, remimazolam will be used first and then switched to ciprofol. A stabilization and washout period of approximately 45 to 60 minutes will be used after drug transition before the second monitoring window whenever surgical conditions allow.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 75 years. 2. Scheduled to undergo elective spine surgery. 3. Planned intraoperative monitoring with MEP and SEP/SSEP. 4. Expected surgical duration sufficient to complete two study drug periods and intraoperative monitoring windows, preferably at least 3.5 to 4 hours. 5. American Society of Anesthesiologists physical status I to III. 6. Able to provide written informed consent, or consent provided by a legally authorized representative where applicable.
Exclusion criteria
1. Known allergy or contraindication to ciprofol, remimazolam, benzodiazepines, propofol-related formulations, opioids, or relevant excipients. 2. Severe preoperative motor or sensory deficit preventing interpretable target MEP or SEP baseline recordings. 3. Implanted cardiac pacemaker, skull defect, or other condition considered unsuitable for transcranial electrical stimulation. 4. Severe neuromuscular disease, poorly controlled epilepsy, severe cognitive impairment, or inability to complete postoperative neurological assessment. 5. Severe hepatic or renal dysfunction, severe hemodynamic instability, shock, or requirement for high-dose vasoactive medications before enrollment. 6. Long-term benzodiazepine, sedative-hypnotic, antiepileptic drug use, or drug/alcohol dependence that may substantially alter anesthetic response. 7. Expected need for continuous deep neuromuscular blockade during surgery, preventing valid MEP monitoring. 8. Any other condition judged by the investigators to make participation unsuitable or unsafe.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Within-participant difference in lower-extremity MEP peak-to-peak amplitude between ciprofol and remimazolam periods | During surgery, at predefined stable monitoring windows under each study drug; up to 6 hours | Lower-extremity target-muscle motor evoked potential peak-to-peak amplitudes will be recorded during stable intraoperative monitoring windows under ciprofol and remimazolam. The primary analysis will compare log-transformed MEP amplitude or amplitude ratio between the two drug periods within the same participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Within-participant difference in lower-extremity SEP amplitude | During surgery, at predefined stable monitoring windows under each study drug; up to 6 hours | Lower-extremity somatosensory evoked potential amplitudes will be compared between the ciprofol and remimazolam periods. |
Outcome results
None listed