Intraoperative intensive blood pressure management strategy and the outcome of patients who had an acute ischaemic stroke undergoing endovascular treatment under general anaesthesia: study protocol for a prospective randomised controlled trial

Study population

Patients admitted to the emergency department of our hospital from September 2023 to September 2026 with AIS and large vessel occlusion confirmed by cranial imaging examination, who require EVT under general anaesthesia, will be screened and enrolled. Prior to surgery, patients or their legal representatives will be fully informed about the objectives, risks and benefits of this study. Written informed consent will be obtained from the patients’ legal representatives. The investigators will complete the case report form in accordance with the listed items, which include age (in years), sex (male or female), height, weight and ASA classification. Patients who do not meet the inclusion criteria will be excluded. Additionally, enrolled patients have the right to discontinue and withdraw from the trial at any time, but must provide accurate medical history and respond to the investigator’s questions. The patients’ personal data will be protected and stored by the investigator in a numbered and secure cabinet.

Inclusion criteria

To be eligible for inclusion in the study, participants must meet all of the following criteria:

• 18 years old ≤age ≤75 years old.

• Clinical diagnosis of AIS with imaging evidence of large vessel occlusion in the anterior or posterior circulation. Confirmation of an intracranial large vessel occlusion of the anterior circulation, specifically within the intracranial segment of the internal carotid artery, the M1 segment of the middle cerebral artery (M1), and the proximal M2 segment of the middle cerebral artery (M2), must be achieved through the implementation of computed tomography angiography imaging. Haemorrhage has to be ruled out by CT or MRI imaging.

• Within 24 hours of stroke onset.

• Undergoing EVT under general anaesthesia.

• ASA classification II-III.

• Body mass index 18.5–30 kg/m².

Exclusion criteria

Potential subjects were excluded from the study if they met any of the following criteria:

• Patients who had an AIS with pre-existing severe neurological or psychiatric disorders.

• ASA classification IV-V.

• Structural heart disease or severe arrhythmia.

• History of stroke.

• Allergy to any narcotic drug or any other excipients.

• Transplant surgery or transplant patients.

• Patients with aortic isthmus stenosis and arteriovenous shunts (exception: patients with haemodynamically inactive dialysis shunts).

• Women who are breast feeding.

• Currently participating in other clinical trials that may affect clinical prognosis evaluation.

• Patients or their family members refused to participate.

Elimination criteria

• Change of operation method, without intravascular thrombectomy.

• Patients and their families refused to participate after the study began.

Randomisation and blinding

To avoid selection bias, this study employed randomisation and allocation concealment. The randomisation and concealed allocation were conducted by a medical statistician prior to the commencement of the trial. Patients were randomly assigned in a 1:1 ratio to either the intensive blood pressure management group (Intensive group) or the traditional blood pressure management group (Traditional group) using a computer-generated random number table. The randomisation sequence was generated based on a minimisation algorithm to ensure balance of key influencing factors. Patients were also stratified according to the following criteria: (1) time from onset to recanalisation (stroke ≤6 hours, 6 hours <stroke ≤12 hours, 12 hours <stroke ≤18 hours, and 18 hours <stroke ≤24 hours); (2) baseline National Institute of Health Stroke Scale (NIHSS) score (<17, ≥17); (3) according to the age of patients (18 years ≤age <35 years, 35 years ≤age < 60 years, 60 years ≤age <75 years).

The study participants were divided into several groups: the research coordinator, clinical anaesthesia group, evaluation and follow-up group and data statistical analysis group. A double-blind method was used to ensure impartiality. The study coordinators were responsible for screening and randomly assigning patients, as well as overseeing the study process and coordinating personnel and materials. Meanwhile, the clinical anaesthesia team strictly adhered to the research protocol and recorded relevant data during each operation, without making any unauthorised changes to the management approach. Subsequently, the evaluation and follow-up group assessed the patients’ condition, symptoms and signs after each operation, conducting necessary follow-up tasks related to the study. Following completion of the study, the data statistical analysis group promptly organised and analysed the collected data. Throughout the study, only the research coordinators and members of the clinical anaesthesia team had knowledge of the patient grouping and specific details regarding intraoperative patient haemodynamic management. This information was kept confidential from the evaluation and follow-up team, data statistical analysis team, patients and their families. Moreover, the laptop used for data collection was password protected and managed by members of the statistical analysis group.

Anaesthesia management

All subjects who met the study’s inclusion and exclusion criteria were admitted to the operating room after randomisation. Peripheral venous access was promptly established, and a balanced fluid infusion was administered intravenously. The rate of infusion was carefully adjusted based on the duration of fasting following the patient’s admission to the room. ECG monitoring, including non-invasive blood pressure, oxygen saturation and ECG, was initiated. The radial artery was punctured to monitor blood pressure changes, and vital signs before anaesthesia induction were recorded. Intravenous injections of midazolam 0.05 mg/kg, etomidate 0.3 mg/kg, rocuronium 0.6 mg/kg and sufentanil 0.5 µg/kg were administered. The rapid sequence induction and intubation strategy was implemented in this clinical setting. Throughout the entire operation, a temperature probe was placed through the nose to monitor the temperature of the middle part of the oesophagus. Patients undergo routine temperature protection strategies throughout the entire surgical procedure in accordance with our institutional protocol.

Anaesthesia was maintained with propofol 5 mg/(kg h) and remifentanil 0.2 µg/(kg min). During the perioperative period, the clinical anaesthesia team adjusted the continuous infusion dose of anaesthetic agent as needed based on the patient’s condition and the requirements of the operation. Haemodynamic parameters, including heart rate and blood pressure, will be diligently monitored to ensure stability. If needed, vasopressors such as phenylephrine or norepinephrine, as well as antihypertensives like urapidil hydrochloride or nicardipine hydrochloride, will be carefully considered to maintain stable haemodynamics while prioritising patient safety. Additionally, detailed documentation will be maintained regarding the dosage and timing of the administered vasopressors and antihypertensives. Arterial blood gas, arterial partial pressure of oxygen (PaO₂), arterial partial pressure of carbon dioxide (PaCO₂) and blood glucose levels were assessed both after induction of anaesthesia and at the conclusion of the surgical procedure.

After the surgical procedure, all administration of anaesthetics, both intravenous and inhaled, was promptly discontinued. To counteract any remaining muscle relaxants, neostigmine combined with atropine was administered intravenously. Additionally, flumazenil was intravenously given to reverse the sedative effects of midazolam. During the anaesthesia recovery phase, the SBP of patients who underwent vascular recanalisation was carefully controlled, maintaining it within the range of 120–160 mm Hg. The vasoactive agents employed to regulate blood pressure were the same as those used during the maintenance period of anaesthesia. Extubation of the endotracheal tube was performed once the patient’s respiratory function had sufficiently recovered, indicated by a tidal volume of 300 mL or more, and oxygen saturation remained above preoperative levels. On transfer to the postoperative ward, the patient’s circulatory management continued to maintain a SBP within the range of 120–160 mm Hg. Vasoactive agents were used as needed for adjustments, and the patient’s fluid intake and output were regulated according to their specific medical condition.

All thrombectomy procedures were provided by specialist interventional radiologists. Device choice and thrombectomy technique were at the discretion of the interventional radiologist. The results of recanalisation were evaluated by interventional radiologists according to the expanded Treatment In Cerebral Ischemia Scale, and the recanalisation was effective if it exceeded grade 2b.

Outcomes

Statistical analysis

The intention-to-treat principle will be used in the analysis of the results in this study. Baseline data will be calculated based on the group to which the patients were randomised. For patients who dropped out, data from the time of randomisation until the last available data will be included in the analysis. The primary outcome and classified secondary outcomes will be analysed using the χ² test. For small sample size analysis, Fisher’s test can be used. Continuous endpoints, such as the 90-day EQ-5D, will be described as means or medians. If the data are skewed, the Wilcoxon test will be used. Otherwise, mixed models will be used to analyse health utility scores over time. The main analysis will not adjust for confounding factors. Safety data will be analysed using descriptive statistics. The reporting of any serious adverse event, the occurrence of selected serious adverse events and the interruption of the assigned treatment due to a serious adverse event will be classified using Medical Dictionary for Regulatory Activities terms. The heterogeneity of the primary endpoint event will be assessed based on the following stratification factors: age (18 years ≤age ＜35 years, 35 years ≤age＜60 years, 60 years ≤age＜75 years), time from symptom onset to mechanical thrombectomy (stroke ≤6 hours, 6 hours <stroke ≤12 hours, 12 hours <stroke ≤18 hours and 18 hours <stroke ≤24 hours), systolic and diastolic blood pressures (above or below the mean), race, putative AIS type and baseline NIHSS score (above or below the median).

The statistical analysis will be described in a prespecified statistical analysis plan and will include two interim analyses. The first interim analysis will be performed when 30% of the 90-day follow-up data has been collected, and the second interim analysis will be performed when 60% of the 90-day follow-up data has been collected. The external Data and Safety Monitoring Board (DSMB) will be governed by the Haybittle-Peto rule, with an alpha of less than 0.001 considered to indicate a significant effect at the interim analysis. The conventional significance level (alpha=0.05) will be used for the last interim analysis, considering that only two interim analyses will be performed and subsequent analyses will require further confirmation. The DSMB will regularly monitor serious adverse events (eg, death, symptomatic intracranial haemorrhage and neurological deterioration), and any occurrence of excess serious adverse events will trigger a discussion about study termination.