Effects of ciprofol on postoperative delirium and outcomes in older patients undergoing major thoracic surgery: protocol for a multicentre, prospective, single-blinded, randomised controlled study

Abstract

Introduction

Postoperative delirium (POD) is a notable complication in older adults undergoing major thoracic surgery and is associated with poor clinical outcomes. Ciprofol, an innovative sedative known for its haemodynamic stability, holds the potential to lower the risk of POD. However, high-quality evidence supporting this claim is limited. The objective of this study is to evaluate the effect of ciprofol compared with propofol on the incidence of POD and postoperative outcomes in older patients undergoing thoracic surgeries.

Methods and analysis

This multicentre, prospective, single-blinded, randomised controlled trial will recruit patients aged ≥65 years scheduled for elective thoracoscopic lobectomy or segmentectomy, with an anticipated anaesthesia duration of at least 2 hours. Participants will be randomised to receive either ciprofol (0.25–1.5 mg/kg/hour) or propofol (1–6 mg/kg/hour) in a 1:1 ratio. The primary outcome is the incidence of POD within 7 days postoperatively, assessed via the three-dimensional confusion assessment method. Secondary outcomes include emergence delirium assessed using the confusion assessment method for the intensive care unit, the incidence of combined adverse events during induction and maintenance of anaesthesia, duration of intraoperative hypotension, minimum mean intraoperative arterial pressure, duration of Wavelet Index <40, other adverse events identified during the follow-up period, length of stay, first exhaust time and postoperative first time to taking food. A non-inferiority margin of 5% is applied for sample size calculation, yielding a total of 214 participants, adjusted for a 10% attrition rate.

Ethics and dissemination

Approval on ethical grounds has been received from the ethics committee of Xuanwu Hospital, Capital Medical University (LinYanShen (2024)-NO.201–003-Revised V.1). We will publish the findings in peer-reviewed journals.

Trial registration number

NCT06674226.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• The study protocol will more accurately assess the effects of the two sedatives on postoperative delirium (POD) while potential POD risks will be strictly controlled.

• The study is conducted in multiple centres, which helps to include a more diverse population and clinical practice settings, thereby enhancing the external validity of the study results.

• The limitations of the study are the brief follow-up duration (until 7 days postoperatively or until discharge) and the use of a single assessment scale for POD.

Background

Postoperative delirium (POD) is characterised as an acute central nervous system syndrome that frequently results in a range of adverse clinical outcomes, including mortality. Older adults constitute a high-risk population for POD.¹ The incidence of POD in older patients undergoing non-cardiac surgery is highly variable, with published rates spanning from 6.1% to 57.1%. The overall incidence rate in this population is estimated to be around 11.1%.²

Several factors contribute to the susceptibility of older patients to POD. Based on these factors, both surgery and anaesthesia can elevate the incidence of POD in this population. Deep sedation, persistent hypotension and postoperative sleep disturbances may heighten the risk of POD occurrence in older patients.³,⁵ At present, there are limited data available to justify the recommendation of particular anaesthetic agents or their dosages for mitigating the risk of POD in older patients.

Ciprofol is a Category 1 innovative drug that was independently developed in China and possesses globally proprietary intellectual property rights. It has been widely used in anaesthesia and critical care. Pre-market phase I-III and post-market data indicate that throughout the administration of general anaesthesia, ciprofol has less impact on haemodynamics and provides a more stable anaesthesia depth compared with propofol.⁶,⁸ Relevant studies have demonstrated that ciprofol is associated with a significant reduction in the incidence of intraoperative hypotension while offering more stable intraoperative haemodynamics and improved brain oxygenation in comparison to propofol.⁹ Currently, the impact of various sedative drugs on the POD incidence in older adults remains elusive. Key strategies identified for mitigating the risk of delirium include meticulous intraoperative haemodynamic optimisation, precise titration of anaesthetic depth guided by processed wavelet electroencephalogram analysis, and comprehensive multimodal analgesia aimed at minimising surgical stress. In comparison to an analogous single-centre study on POD in thoracic surgery, these interventions facilitate a more accurate assessment of the impact of sedative medications on POD, which highlights the innovative aspect of our multicentre trial protocol.⁹ Therefore, the purpose of this research is to evaluate the comparative effects of ciprofol or propofol on the incidence of POD and other outcomes in the older population undergoing thoracic surgery.

Methods and analysis

Study design

This is a prospective, single-blinded, randomised controlled trial. Individuals aged 65 years or greater slated for elective thoracoscopic lobectomy and lung segmentation under general anaesthesia with an estimated duration of anaesthesia of 2 hours or more, will be enrolled in this study. Participants will be randomly assigned to two groups at a 1:1 ratio: the ciprofol group and the propofol group. A total of 214 patients will be recruited. Study data for patients will be recorded from before surgery until 7 days postoperatively or until discharge. The primary outcome is the incidence of POD. A study flowchart is presented in figure 1. The study is initiated by the Department of Anesthesiology, Xuanwu Hospital, Capital Medical University. Study monitoring, data management and data analysis are the responsibility of the Bethune Foundation. Other sites involved in the research are: The First Hospital of Hebei Medical University, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, the Third Xiangya Hospital of Central South University, Xiangya Hospital of Central South University, Affiliated Drum Tower Hospital of Nanjing University, the First Affiliated Hospital of Nanchang University and The First Affiliated Hospital, Jinan University.

Figure 1. Design of the study.

Trial status

This study has been reviewed and approved by the ethics committee of Xuanwu Hospital, Capital Medical University, on 10 December 2024, and has been registered on ClinicalTrials.gov (registration date: 31 October 2024). From December 2024 to June 2026, 214 patients undergoing scheduled thoracoscopic lobectomy or segmentectomy will be recruited. This study is recruiting patients now.

Participants

Inclusion criteria

1. Aged 65 years or older, no gender restrictions.

2. Elective thoracoscopic lobectomy and segmental lung resection are planned, and the estimated duration of anaesthesia (from the beginning of anaesthesia to the end of surgery) is ≥2 hours.

3. American Society of Anesthesiologists (ASA) score is Grade I-III.

4. A body mass index (BMI) of 18.5–29.9 kg/m² (BMI=weight (kg)/height (m)²).

5. Postoperative hospital stay more than 72 hours.

6. Ethical, patients voluntarily take the test and sign the informed consent.

Exclusion criteria

1. Emergent surgery, hypovolaemia, shock or coma.

2. In addition to general intravenous anaesthesia, other anaesthesia methods should be combined, such as inhalation anaesthesia, epidural anaesthesia, peripheral nerve block, but it is not necessary to exclude patients with local infiltration of local anaesthetic incision.

3. Serious cardiovascular disease, including a history of myocardial infarction within 6 months, bradycardia (resting heart rate <50 beats/min); patients with hypertension whose blood pressure is not satisfactorily controlled (seated systolic blood pressure ≥160 mm Hg during screening, and/or diastolic blood pressure ≥100 mm Hg during screening); sitting systolic blood pressure ≤90 mm Hg during the screening period; a history of severe heart valve disease.

4. Abnormal liver function, glutamic oxaloacetic transaminase (AST) and/or glutamic pyruvic transaminase (ALT) ≥2.5×ULN, TBIL≥1.5×ULN.

5. Abnormal renal function, urea or urea nitrogen ≥1.5×ULN, blood creatinine greater than the upper limit of normal.

6. Glycated haemoglobin ≥8.5%, fasting blood glucose ≥180 mg/dL (10 mmol/L), blood glucose ≥270 mg/dL (15 mmol/L) 1 hour after meals or blood glucose ≥216 mg/dL (12 mmol/L) 2 hours after meals.

7. Patients with type I and type II expiratory failure.

8. Preoperative anaemia (haemoglobin ≤90 g/L), thrombocytopenia (platelet (PLT) ≤80×10⁹/L), hypoproteinaemia (albumin (Alb) ≤30 g/L).

9. A history of drug abuse and/or alcohol abuse within the 2 years prior to screening, with alcohol abuse being an average consumption of more than 2 units of alcohol per day (one unit=360 mL beer or 150 mL of 45 mL liquor or wine with an alcohol concentration of 40%).

10. Patients with neurological diseases (stroke, Alzheimer’s disease, Parkinson’s disease, mental illness, myasthenia gravis, etc) within 6 months, psychiatric diseases (schizophrenia, mania, bipolar disorder, insanity, etc), long-term history of taking psychiatric drugs and cognitive impairment (using Mini-Mental State Examination (MMSE).¹⁰

11. Patients who take sedative sleeping drugs and antiepileptic drugs for a long time.

12. Allergic to the investigational drug or contraindicated.

13. Enrolment in another investigational drug trial within the 3 months preceding screening.

14. Patients who refuse or are unable to cooperate with the study.

15. Other conditions that the investigator considers inappropriate to participate in this study.

Dropout criteria

1. Patients undergoing a second surgery during the follow-up period.

2. Surgery type is changed to open surgery.

3. Severe intraoperative hypoxaemia (arterial partial pressure of oxygen (PaO₂) <60 mm Hg or pulse oxygen saturation (SpO₂) <90% for ≥5 min) or repeated unsuccessful placement of the double-lumen tube during intubation (≥3 attempts).

4. Patients refuse surgery or surgical cancellation after randomisation.

5. Patients with a postoperative hospital stay of <3 days, or those missing delirium assessments on postoperative days 1–3 for other reasons.

Training for staff on delirium assessment

Training on the study protocol will be provided to study personnel prior to the study, ensuring compliance with Good Clinical Practice guidelines. In addition, they will undergo standard training for assessing delirium using the confusion assessment method for the intensive care unit (CAM-ICU)¹¹ and the three-dimensional (3D)-confusion assessment method (3D-CAM).¹²

The CAM-ICU will be administered in the post-anesthetic care unit (PACU) using its standard two-step procedure to assess emergence delirium. First, sedation depth will be evaluated using the Richmond Agitation Sedation Scale (RASS).¹³ This 10-point scale measures states ranging from anxiety and agitation (+1 to +4) to sedation and coma (−1 to −5), with a central point (0) representing an alert and calm state. If the score is −4 or −5, the delirium assessment should be discontinued; if the score is greater than or equal to −3, continue with the delirium assessment. Second, delirium will be assessed using the CAM-ICU, which recognises four characteristics of delirium:

1. Acute change or fluctuation in mental status.

2. Inattention.

3. Disorganised thinking.

4. Altered level of consciousness.

Following a diagnosis of delirium in patients using the CAM-ICU scale, the delirium subtype is determined based on the RASS score. Scores ranging from +1 to +4 are indicative of hyperactive delirium, scores between 0 and −3 denote hypoactive delirium and fluctuations between positive and negative values characterise mixed delirium.

The 3D-CAM incorporates four core diagnostic features that are assessed to identify delirium (online supplemental appendix 1).¹⁴ The diagnosis of delirium requires the simultaneous presence of features 1 and 2, in addition to the identification of either feature 3 or feature 4.

Randomisation and blinding

The study will employ a centre-stratified randomisation design. Eligible participants from each centre will be assigned equally (1:1 ratio) to either the ciprofol or propofol group using SAS software. Subjects identifying eligibility will receive the randomisation. The investigator will log into the central randomisation system (Interactive Web Response System, [IWRS]) to obtain the subject randomisation number and group information.

This study will employ participant and evaluator-blinded research methods. Blinding regarding treatment assignment will be maintained for both patients and the investigators responsible for follow-up, outcome assessment and data analysis.

Independent evaluation of the investigator

In this trial, the evaluator and the personnel responsible for drug dosing will operate independently. Randomisation and drug administration will be conducted by the drug dosing personnel, while follow-up assessments of primary and all secondary outcomes will be carried out by the evaluator.

Study implementation

Screening period

Information regarding the study protocol and the potential risks of involvement will be conveyed to all participants. Written consent will then be acquired from each one. Demographic data will be collected, including gender, date of birth, ethnic group, height, weight, history of comorbidities, alcohol consumption and special medications. Preoperative baseline blood pressure and heart rate will be measured. Document laboratory tests, including complete blood count, biochemical profile, echocardiography, ASA, MMSE and age-adjusted Charlson Comorbidity Index. Patients will be evaluated according to the screening manual to exclude ineligible patients. After confirmation of eligibility, each participant will be assigned a randomisation number. Investigators will administer the treatment according to group assignment.

Anaesthesia and monitoring methods

The schematic diagram of the surgical medication protocol is illustrated in figure 2. Routine preoperative fasting should be maintained for 6–8 hours. Patients without gastrointestinal motility disorders may ingest carbohydrate-containing clear fluids orally up to 400 mL at least 2 hours before surgery. Administration of long-acting sedatives and opioid medications should be avoided preoperatively. Routine monitoring will be established when the patient entry into the operating room, including continuous ECG, SpO₂, non-invasive blood pressure, Wavelet Index (WLi) and Pain Threshold Index (PTi). An intravenous catheter will be inserted into a peripheral (forearm) or central vein to facilitate intravenous infusion. Insertion of an intra-arterial cannula into the radial artery will allow for continuous invasive arterial pressure monitoring and arterial blood gas analysis. Parecoxib sodium (40 mg) will be administered intravenously 30 min prior to the commencement of surgery, or flurbiprofen axetil (50 mg) will be given 6–7 min before the surgical procedure. All patients will receive a fluid preload of 3 mL/kg over a period of 10 min, using either Lactated Ringer’s solution or Sodium Acetate Ringer’s solution. 5 min prior to the induction of anaesthesia, 40 mg of methylprexone and one of the following 5-HT₃ receptor antagonists—dolasetron (12.5 mg), ondansetron (4 mg), tropisetron (2 mg) or palonosetron (0.075 mg)—will be administered according to their recommended timing of administration.

Figure 2. Schematic diagram of intraoperative drug administration protocol. MOAA/S, Modified Observer’s Assessment of Alertness/Sedation; PPV, pulse pressure variability; SVV, stroke volume variability.

Anaesthesia induction

During the induction period, patients will undergo preoxygenation for 3 min using delivery of 100% oxygen through a face mask at a flow rate of 6 L/min. Subsequently, they will receive an intravenous bolus injection of sufentanil at a dosage of 0.3–0.5 µg/kg over 10–20 s. Following a 1 min observation period (±10 s), the treatment protocol involves administering an initial dose of ciprofol at 0.25 mg/kg over 10–20 s to patients in the ciprofol group. For the propofol group, the initial dose is 1.0 mg/kg of propofol. The Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scoring will be conducted every 30 s (±10 s) following the injection.¹⁵ If the MOAA/S score remains ≥1 at 1 min (±10 s) after the initial dose, additional ciprofol or propofol (33% of the initial dose) will be administered over a maximum of 10 s until MOAA/S score of 0 is achieved, which is defined as a successful induction. Following successful induction, rocuronium at a dosage of 0.6–0.9 mg/kg will be administered immediately. After 1 min (±10 s), remifentanil at a dosage of 2–3 µg/kg will be administered to target a PTi between 40 and 60, then insertion of a double-lumen endotracheal tube will be carried out. Concurrently, on administration of propofol or ciprofol, norepinephrine infusion will be initiated at an initial dose of 0.03–0.05 µg/kg/min. The norepinephrine dosage should be titrated upward or downward to maintain intraoperative blood pressure fluctuations within±10% of baseline values.

Anaesthesia maintenance and postoperative analgesia

Patients will receive a continuous infusion of ciprofol (0.25–1.5 mg/kg/hour) or propofol (1–6 mg/kg/hour) for maintenance, depending on their group assignment. Adjustment to sedative dosages will be made to maintain the WLi within the range of 40–70. Remifentanil infusion rate will be 0.2–0.5 µg/kg/min initially, and then adjusted according to the PTi, which will be maintained within the range of 40–70. If an intraoperative nociceptive surge occurs (PTi>70), a remifentanil bolus of 0.5–1 µg/kg will be administered intravenously when triggered by haemodynamic responses such as tachycardia or hypertension. If PTi remains above 70 after 1 min observation period, equivalent bolus doses will be repeated until the target range of PTi (40–70) is achieved. The maintenance dose of norepinephrine during surgery will be adjusted based on changes in blood pressure, ensuring that average arterial pressure fluctuations are maintained within±10% of baseline value. Rocuronium will be administered at a dose of 0.2–0.3 mg/kg intraoperatively as dictated by surgical requirements. The administration of all anaesthetic agents will cease at the end of the surgical procedures. Norepinephrine will be gradually tapered after the patients awaken. Patients will receive patient-controlled intravenous analgesia using 30 mg of oxycodone diluted in 100 mL of normal saline, administered without loading dose. The maximum dose per hour is 0.1 mg/kg. The self-administration capacity and locking time will be set at 1.0 mg and 5 min, respectively. Online supplemental table S1 summarises the schedule detailing enrolment, interventions and assessments.

Anaesthesia management

1. The pressure controlled ventilation volume guaranteed (PCV-VG) mode will be used for mechanical ventilation, with an air/oxygen mixture administered at a fractional inspired oxygen between 40% and 100%. Tidal volume settings will be 6–8 mL/kg (dual-lung) or 4–6 mL/kg (one-lung ventilation). The respiratory rate will be modified based on the concentrations of end-tidal carbon dioxide, which will range between 35 and 40 mm Hg.

2. Arterial blood gas analysis will be monitored preoperatively, at 15 min of one-lung ventilation and at 10 min after extubation. Arterial blood gas analysis will be performed as needed intraoperatively. Additionally, alveolar recruitment manoeuvres will be implemented at least at the end of surgery and before tracheal extubation.

3. Core temperature will be maintained above 36°C, and warming measures will be routinely used.

4. Goal-directed fluid therapy combined with prophylactic vasoconstrictor drugs will be implemented to maintain stroke volume variability or pulse pressure variability <13% (<10% during one-lung ventilation), while keeping blood pressure fluctuation within±10% of the baseline level.

5. The heart rate will be maintained at 80%–120% of the baseline heart rate. When the heart rate exceeds 120% of the baseline heart rate or is less than 80%, the underlying cause will be identified and targeted interventions will be implemented.

6. Blood glucose should be maintained within 70–180 mg/dL (3.9–10.0 mmol/L). When blood glucose exceeds 180 mg/dL (10.0 mmol/L), insulin therapy should be initiated.

7. 10 min before incision and 30 min (±10 min) before skin closure, oxycodone (0.05–0.1 mg/kg) will be administered intravenously. Before skin incision and when closing the incision at the end of surgery, local anaesthetic (0.5%–1.0% lidocaine combined with 0.25%–0.50% ropivacaine, 10–20 mL) will be used for local incision infiltration analgesia.

Recovery of anaesthesia

The choice between sugammadexand neostigmine for reversing neuromuscular blockade reversal will be determined by anaesthesiologists. Vasoactive agents will be administered to maintain heart rate fluctuations within±20% of baseline and blood pressure fluctuation within±10% of baseline values. Perioperative management will conclude on admission to the PACU, where PACU physicians assume responsibility for haemodynamic monitoring. A blinded anaesthesia practitioner will evaluate emergence delirium using the CAM-ICU at 20 min (±1 min) post-extubation within the PACU.

Primary outcome

The incidence of POD is the primary outcome.

A dedicated follow-up staff member, who is blinded to the trial and has received specialised training, will assess patients using the 3D-CAM scale in the morning from 08:00 to 10:00 and in the evening from 18:00 to 20:00 every day from postoperative day 1 through day 7 or on the day of discharge (whichever occurred first).

Secondary outcomes

Secondary outcomes include:

1. Incidence of emergence delirium.

2. The incidence of combined adverse events during induction and maintenance of anaesthesia.

3. Duration of intraoperative hypotension.

4. Minimum mean intraoperative arterial pressure.

5. Duration of WLi<40.

6. Other adverse events identified during the follow-up period, except POD.

7. Hospital length of stay.

8. First exhaust time.

9. Postoperative first time to taking food.

Adverse events

Online supplemental table S2 presents the definitions of systemic adverse events. These events are briefly described as follows:

Circulatory system adverse events:

1. Bradycardia.

2. Tachycardia.

3. Hypotension.

4. Hypertension.

5. Frequent premature ventricular contractions.

6. Atrial flutter/fibrillation: confirmed by ECG.

7. Ventricular fibrillation/pulseless ventricular tachycardia/cardiac arrest.

8. Conduction abnormalities/heart block.

9. Acute myocardial ischaemia.

10. Acute myocardial infarction.

11. Pulmonary embolism.

12. Congestive heart failure.

13. Acute heart failure.

14. Deep vein thrombosis.

Respiratory system adverse events:

1. Pneumonia.

2. Pulmonary oedema.

3. Respiratory failure.

4. Bronchospasm.

5. Atelectasis.

6. Pleural effusion.

Nervous system adverse events:

1. Intraoperative awareness.

2. Acute stroke.

3. Delayed emergence.

Digestive system adverse events:

Postoperative gastrointestinal dysfunction/postoperative ileus.

Urinary system adverse events:

Acute kidney injury.

Serious adverse events

Serious adverse events (SAEs) are defined as unexpected medical incidents resulting in mortality, life-threatening conditions, extended hospital stay, permanent disability or other severe outcomes.

On occurrence of an SAE, the study intervention will be terminated, and treatment will be initiated immediately. Submission of written documentation to the hospital’s ethics committee (EC) is required within 24 hours. In the event of a death related to the study intervention, the study will be terminated and notification must be sent to the EC without delay. All SAEs will be followed up until complete resolution or the end of treatment.

Sample size estimation

Based on our preliminary study conducted in four centres, a total of 51 cases were enrolled, with 27 in the ciprofol group and 24 in the propofol group. The incidence of POD in the ciprofol group was 3.7% (1/27), while it was 8.3% (2/24) in the propofol group. A non-inferiority margin of 5% was established with a two-sided alpha level of 0.05, a power of 80% and a 1:1 sample size ratio between the groups. Using PASS V.15.0 software, the sample size was calculated using the ‘Non-Inferiority Tests for the Difference Between Two Proportions’ module, employing the Z-test using separate variances. The calculation determined that 96 participants would be required per group (totalling 192). The final sample size is adjusted to 214 participants to compensate for a 10% dropout rate.

Data analysis

Statistical analyses will be conducted using SAS V.9.4 and R statistical software. The statisticians will be blinded to the clinical trial and will have no knowledge of patient group allocation. Continuous variables will be presented as the mean±SD (mean±SD). The χ² test will be used to assess rate incidence between the two groups. For continuous variables exhibiting normal distributions, a t-test will be applied, while non-parametric tests will be employed for all other variables. One-way analysis of variance will be employed for comparisons between groups. A p value<0.05 will be considered statistically significant.

Ethics and dissemination

Approval on ethical grounds has been received from the ethics committee of Xuanwu Hospital, Capital Medical University (LinYanShen(2024)-NO. 201–003-Revised V.1). Any modifications to the protocol will be submitted for EC review and approval. The study has been registered at ClinicalTrials.gov (NCT06674226). Each patient will be required to provide written informed consent. For those patients incapable of providing consent, it will be obtained from their surrogate. This research protocol complies with Standard Protocol Items: Recommendations for Interventional Trials 2013 guidelines. We will publish the findings in peer-reviewed journals.

Data management and monitoring

Data collection will be performed by independent research personnel using case report forms (CRF). Strict compliance with the standard operating procedure and study protocol is mandatory for all researchers. Data entries must exhibit timeliness, directness, accuracy, clarity and include signature and date. Any corrections made to data in CRF or source documents must be dated, signed and accompanied by a rationale. The original entries must remain legible and unaltered.

Investigators at each site will enter data into the electronic data capture (EDC) system on completion of the clinical trial. Clinical Research Associates will perform source data verification to ensure consistency between the EDC data and source documents (medical records and laboratory reports).

The data management team and medical reviewers will conduct an item-by-item review of the EDC data. For any discrepancies or unclear entries, they will raise queries within the EDC system. Investigators must then cross-check the original data, confirm or correct the entries and provide explanations until all queries are resolved. The data manager or medical reviewer will subsequently close the queries.

Once the database is thoroughly reviewed and validated, the principal investigator, sponsor and statistical analysis team will jointly lock the database. After locking, no further modifications to the dataset are permitted.

Strengths and limitations

There are several strengths in our protocol. The study protocol will more accurately assess the effects of the two sedatives on POD while potential POD risks are strictly controlled for. In addition, the study is conducted in multiple centres, which helps to include a more diverse population and clinical practice settings, thereby enhancing the external validity of the study results. However, the limitations of the study are the brief follow-up duration (only until 7 days postoperatively or until discharge) and the use of a single assessment scale for POD.

Discussion

POD is a significant clinical concern, particularly among older adults, who represent a high-risk population. Optimising perioperative management in this demographic to reduce the incidence of POD holds significant clinical value. Currently, only studies with small sample sizes have confirmed the impact of the sedatives ciprofol and propofol on the incidence of POD in older adults. A single centre, randomised controlled trial comparing ciprofol and propofol for total intravenous anaesthesia among the older population undergoing thoracoscopic lung cancer surgery revealed that ciprofol did not increase POD incidence, which is consistent with our pre-experimental results.⁹ Our clinical study employs several strategies to strictly control known risk factors for POD, such as comprehensive and meticulous intraoperative haemodynamic management, multimodal analgesia management and optimised warming measures, to effectively quantify the impact of propofol and ciprofol on POD in older adults.

In conclusion, this study will evaluate the impact of ciprofol versus propofol on the incidence of POD and other clinical outcomes among the older population undergoing major thoracic surgery. The findings are anticipated to inform anaesthetic selection and the development of neuroprotective strategies within this vulnerable population, ultimately strengthening evidence-based clinical anaesthesia practice.