Brain Neoplasms, Delirium - Postoperative
Conditions
Keywords
Ciprofol, Propofol, Sevoflurane, Postoperative Delirium, Brain Neoplasms, General Anesthesia, Aged, Cognitive Function
Brief summary
This study will compare three anesthesia medicines used to put people into a deep sleep during surgery: ciprofol, propofol, and sevoflurane. All three are commonly used for general anesthesia, but they work in different ways. Ciprofol and propofol are given through a vein. Sevoflurane is breathed in as a gas. After brain tumor surgery, some older adults may develop sudden confusion and memory problems called delirium. Researchers want to learn which of these three medicines is best at preventing delirium and protecting brain function in older adults undergoing brain tumor surgery. About 381 participants aged 65 to 90 will take part. Participants will be randomly assigned to one of three groups. One group will receive ciprofol. Another group will receive propofol. The third group will receive sevoflurane. All participants will receive standard care during and after brain tumor removal. The main goal is to compare how many participants develop delirium within 7 days after surgery. Researchers will also look at how long delirium lasts, how severe it is, thinking and memory skills at 7, 30, 90, and 180 days after surgery, quality of recovery, blood pressure and heart rate during surgery, and treatment safety. Blood tests will be used to measure markers of body stress, inflammation, and nerve cell injury before surgery, 3 hours after surgery, and 1 day after surgery. Researchers will also test thinking and memory with simple questions twice a day for 7 days after surgery. Later follow-up will be done by phone at 30, 90, and 180 days after surgery. This study is designed to explore which anesthesia medicine is safest and best at protecting the brain after surgery in older adults with brain tumors. The results may help doctors choose the best anesthesia for this group of patients in the future.
Interventions
DRUGCiprofol
Ciprofol injectable emulsion (20 mL: 50 mg) administered intravenously for general anesthesia induction and maintenance during elective brain tumor resection. Induction: 0.3-0.4 mg/kg by slow intravenous injection over ≥30 seconds. Maintenance: continuous intravenous infusion at 0.4-2.4 mg/kg/h via infusion pump, beginning after induction and continuing until the end of surgery. Dose adjustments are made based on patient response and hemodynamic monitoring. Total duration depends on operative time.
DRUGPropofol
Propofol injectable emulsion administered intravenously for general anesthesia induction and maintenance during elective brain tumor resection. Induction: 1.5-2.0 mg/kg by slow intravenous injection over ≥30 seconds. Maintenance: continuous intravenous infusion at 4-12 mg/kg/h via infusion pump, beginning after induction and continuing until the end of surgery. Dose adjustments are made based on patient response and hemodynamic monitoring. Total duration depends on operative time.
DRUGSevoflurane
Sevoflurane inhalation solution (volatile liquid) administered via inhalation through a calibrated vaporizer for general anesthesia induction and maintenance during elective brain tumor resection. Induction: 7-8% inhaled concentration with oxygen flow 2-4 L/min until loss of consciousness. Maintenance: inhaled concentration adjusted to 1.0-3.0% and titrated to effect; concentration is gradually reduced beginning 30 minutes before the anticipated end of surgery and discontinued at the end of the procedure. Total duration depends on operative time.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 65 to 90 years, either sex. 2. Scheduled to undergo elective brain tumor resection under general anesthesia. 3. American Society of Anesthesiologists (ASA) physical status I-III. 4. Expected operative time ≥ 2 hours and anticipated postoperative hospital stay \> 48 hours. 5. Able to communicate in Chinese and complete cognitive assessments. 6. Preoperative cognitive function intact: Telephone Montreal Cognitive Assessment (T-MoCA) score ≥ 18 and Confusion Assessment Method (CAM) negative. 7. No use of analgesic or sedative medications on the day before surgery. 8. Able to provide informed consent and willing to comply with postoperative follow-up through 180 days.
Exclusion criteria
1. Preoperative use of medications that may affect postoperative cognition (e.g., long-term benzodiazepines, antidepressants, antipsychotics, or chronic sedative-hypnotic use that cannot be paused). 2. Preoperative delirium, dementia, diagnosed severe psychiatric disorder, or existing central nervous system disease. 3. History of alcohol addiction or drug abuse; suspected or confirmed long-term use of narcotic analgesics or sedatives. 4. Severe visual, auditory, or speech impairment that precludes communication and cognitive testing. 5. Severe cardiopulmonary disease: forced expiratory volume in 1 second (FEV1) or vital capacity \< 50% of predicted; New York Heart Association (NYHA) functional class III-IV; severe hepatic or renal insufficiency (creatinine \> 176 μmol/L, blood urea nitrogen \> 7.1 mmol/L, albumin \< 30 g/L, Child-Pugh class C, or preoperative dialysis). 6. Known difficult airway, malignant hyperthermia susceptibility, or other contraindication to general anesthesia. 7. Hypersensitivity or known allergy to ciprofol, propofol, sevoflurane, or other study-related agents. 8. Severe uncontrolled infection or endocrine disorder. 9. Concurrent participation in another clinical trial. 10. Judged unsuitable for enrollment by the attending surgeon, anesthesiologist, or principal investigator for any other reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Postoperative Delirium Within 7 Days After Surgery as Assessed by the Confusion Assessment Method (CAM) | Postoperative 2 hours, 6-12 hours, and twice daily (08:00-10:00 and 18:00-20:00) from postoperative Day 1 through Day 7 | Delirium is diagnosed using the Confusion Assessment Method (CAM). A positive CAM assessment requires the simultaneous presence of Feature 1 (acute onset and fluctuating course) and Feature 2 (inattention), plus either Feature 3 (disorganized thinking) or Feature 4 (altered level of consciousness). The outcome is reported as the proportion of participants with at least one positive CAM assessment during the 7-day postoperative period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Tracheal Extubation After Cessation of Anesthetic Agents | From end of surgery to extubation in the PACU (measured in minutes) | Time from cessation of all anesthetic agents to removal of the endotracheal tube after the return of adequate spontaneous breathing, airway reflexes, and consciousness. |
| Length of Stay in the Post-Anesthesia Care Unit (PACU) | From PACU admission to PACU discharge (measured in minutes) | Time from admission to the post-anesthesia care unit (PACU) to meeting discharge criteria (Steward recovery score ≥ 4) and transfer to the ward. |
| Change in Mean Arterial Pressure (MAP) From Baseline at 1 Minute After Induction, at Intubation, at Dural Incision, and at End of Surgery | Baseline (pre-induction) and intraoperative time points: 1 minute after induction, at intubation, at dural incision, and at end of surgery | Mean arterial pressure (MAP) is measured continuously via invasive arterial monitoring. Baseline MAP is obtained before anesthesia induction with the participant at rest. Change from baseline is calculated as the value at each intraoperative time point minus the baseline value. Negative values indicate a decrease from baseline; positive values indicate an increase. |
| Duration of Postoperative Delirium in Days During the First 7 Days After Surgery | Postoperative Day 1 through Day 7 | Duration is defined as the time interval from the first positive CAM diagnosis of delirium to the first assessment showing no delirium symptoms (CAM negative) for a continuous period of at least 24 hours. Recorded in days. If delirium persists beyond 7 days, the maximum recorded duration is 7 days. |
| Mean Daily CAM-Severity (CAM-S) Score During the First 7 Days After Surgery | Postoperative Day 1 through Day 7 (twice daily assessments) | The CAM-Severity scale quantifies delirium severity based on CAM features. The 4-item version ranges from 0 to 7 points; the 10-item version ranges from 0 to 19 points. Higher scores indicate more severe delirium. The mean daily score is calculated by averaging all CAM-S scores obtained during each calendar day. |
| Change in Cognitive Function From Baseline as Assessed by T-MoCA at 7 Days After Surgery | Baseline (1 day before surgery) and postoperative Day 7 | The Telephone Montreal Cognitive Assessment (T-MoCA) evaluates cognitive function including attention, memory, language, and orientation. Total scores range from 0 to 22 points, with higher scores indicating better cognitive function. A score of 18 or above indicates normal cognitive function. Change from baseline is calculated as the post-treatment score minus the baseline score; a positive change indicates improvement and a negative change indicates decline. |
| Change in Cognitive Function From Baseline as Assessed by T-MoCA at 30 Days After Surgery | Baseline (1 day before surgery) and postoperative Day 30 | The Telephone Montreal Cognitive Assessment (T-MoCA) evaluates cognitive function including attention, memory, language, and orientation. Total scores range from 0 to 22 points, with higher scores indicating better cognitive function. Change from baseline is calculated as the post-treatment score minus the baseline score; a positive change indicates improvement and a negative change indicates decline. |
| Change in Cognitive Function From Baseline as Assessed by T-MoCA at 90 Days After Surgery | Baseline (1 day before surgery) and postoperative Day 90 | The Telephone Montreal Cognitive Assessment (T-MoCA) evaluates cognitive function including attention, memory, language, and orientation. Total scores range from 0 to 22 points, with higher scores indicating better cognitive function. Change from baseline is calculated as the post-treatment score minus the baseline score; a positive change indicates improvement and a negative change indicates decline. |
| Change in Cognitive Function From Baseline as Assessed by T-MoCA at 180 Days After Surgery | Baseline (1 day before surgery) and postoperative Day 180 | The Telephone Montreal Cognitive Assessment (T-MoCA) evaluates cognitive function including attention, memory, language, and orientation. Total scores range from 0 to 22 points, with higher scores indicating better cognitive function. Change from baseline is calculated as the post-treatment score minus the baseline score; a positive change indicates improvement and a negative change indicates decline. |
| Change in Quality of Recovery From Baseline as Assessed by QoR-15 at 1 Day After Surgery | Baseline (1 day before surgery) and postoperative Day 1 | The 15-item Quality of Recovery scale (QoR-15) assesses physical and psychological recovery after surgery. Each item is scored from 0 (never able to achieve the state) to 10 (always able to achieve the state), with a total score range of 0 to 150. Higher scores indicate better quality of recovery. Change from baseline is calculated as the post-treatment score minus the baseline score. |
| Change in Quality of Recovery From Baseline as Assessed by QoR-15 at 3 Days After Surgery | Baseline (1 day before surgery) and postoperative Day 3 | The 15-item Quality of Recovery scale (QoR-15) assesses physical and psychological recovery after surgery. Each item is scored from 0 (never able to achieve the state) to 10 (always able to achieve the state), with a total score range of 0 to 150. Higher scores indicate better quality of recovery. Change from baseline is calculated as the post-treatment score minus the baseline score. |
| Maximum Richmond Agitation-Sedation Scale (RASS) Score During Post-Anesthesia Care Unit (PACU) Stay | From PACU admission to PACU discharge, with assessments at 2, 30, 60, 90, 120, 150, and 180 minutes after extubation | The Richmond Agitation-Sedation Scale (RASS) assesses the level of consciousness and agitation in the post-anesthesia care unit (PACU). Scores range from -5 (unarousable) to +4 (combative), with 0 indicating alert and calm. Higher positive scores indicate greater agitation; more negative scores indicate deeper sedation. The maximum RASS score is defined as the highest score observed across all serial assessments from admission to the PACU until discharge. A higher maximum score indicates more severe postoperative agitation. |
| Time to Loss of Consciousness Following Start of Anesthesia Induction | During anesthesia induction (measured in minutes) | Time from the start of anesthetic drug administration to loss of eyelash reflex and unresponsiveness to verbal command, indicating successful anesthesia induction. |
| Change in Heart Rate (HR) From Baseline at 1 Minute After Induction, at Intubation, at Dural Incision, and at End of Surgery | Baseline (pre-induction) and intraoperative time points: 1 minute after induction, at intubation, at dural incision, and at end of surgery | Heart rate (HR) is measured continuously via electrocardiogram monitoring. Baseline HR is obtained before anesthesia induction with the participant at rest. Change from baseline is calculated as the value at each intraoperative time point minus the baseline value. Negative values indicate a decrease from baseline; positive values indicate an increase. |
| Change in Serum Superoxide Dismutase (SOD) From Baseline at 3 Hours and 1 Day After Surgery | Baseline (1 day before surgery), 3 hours after surgery, and 1 day after surgery | Serum SOD is measured by standardized laboratory assay as a marker of oxidative stress. Change from baseline is calculated as the postoperative concentration minus the preoperative concentration. Higher levels indicate greater antioxidant capacity. |
| Change in Serum Interleukin-6 (IL-6) From Baseline at 3 Hours and 1 Day After Surgery | Baseline (1 day before surgery), 3 hours after surgery, and 1 day after surgery | Serum IL-6 is measured by standardized laboratory assay as a marker of inflammation. Change from baseline is calculated as the postoperative concentration minus the preoperative concentration. Higher levels indicate greater inflammatory response. |
| Time to Emergence From Anesthesia After Cessation of Anesthetic Agents | From end of surgery to emergence in the PACU (measured in minutes) | Time from cessation of all anesthetic agents to eye opening in response to verbal command or spontaneous movement, indicating recovery of consciousness. |
| Change in Serum S100 Calcium-Binding Protein Beta (S100β) From Baseline at 3 Hours and 1 Day After Surgery | Baseline (1 day before surgery), 3 hours after surgery, and 1 day after surgery | Serum S100β is measured by standardized laboratory assay as a marker of glial cell injury and blood-brain barrier disruption. Change from baseline is calculated as the postoperative concentration minus the preoperative concentration. Higher levels indicate greater central nervous system injury. |
Countries
China
Contacts
CONTACTTingting Wang, Ph.D.
Outcome results
None listed