| 【Background】Propofol has the effects of rapid induction,rapid recovery and reducing cerebral metabolism.It is a commonly used sedative drug for general anesthesia in cerebral endovascular procedures.However,propofol can cause many adverse reactions,the most prominent of which is circulatory depression.Patients with cerebrovascular disorder may suffer from dysfunction of cerebral blood flow autoregulation,and the endovascular treatment changes the physiological state of cerebral blood flow.Therefore,they could be more sensitive to intraoperative hypotension and are exposed to increased risk of major cardiac and cerebrovascular events and other important organ damage.Thus,it is urgent to explore a more ideal sedative drug to replace propofol in the application of cerebral endovascular procedures.Remimazolam,a novel ultra-short acting benzodiazepine,ensures hemodynamic stability relatively for procedural sedation and general anaesthesia,and it was proved noninferior to propofol considering the success rate of sedation.Patients undergoing cerebral endovascular procedures may benefit from the hemodynamic stability of remimazolam general anaesthesia.However,the current evidence of remimazolam being used for general anaesthesia is still limited,especially for the neurosurgical patients.The choice of anesthetic for cerebral endovascular procedures should aim at rapid postoperative awakening time,which is conducive to the prompt neurological examination.However,it is still controversial whether remimazolam is shorter or longer than propofol on time to emergence from general anaethesia,and its effect on postoperative delirium(POD)as a benzodiazepine remains to be verified.Thus,we tend to design and conduct a non-inferiority clinical trial to assess that whether remimazolam would improve the perioperative safety and long-term prognosis of patients undergoing cerebral endovascular procedures without prolonging the time to emergence after general anaesthesia.【Methods】This study is a single-center,randomized,double-blind and non-inferior clinical trial.142 patients undergoing cerebral endovascular procedures were randomly allocated on a 1:1 basis,and received general anaethesia with intravenous injection of remimazolam 0.1 mg/kg and maintained with remimazolam 0.3-0.7 mg/kg/h,or induced with intravenous injection of propofol 1-1.5 mg/kg and maintained with propofol 4-10 mg/kg/h.The primary outcome was the time to emergence from general anaethesia.Secondary outcomes included anesthesia induction and recovery time,hemodynamic stability during anesthesia,postoperative serum inflammatory factor level,the incidence of POD and major complications during postoperative hospitalization,length of hospitalization,mental state at discharge and modified Rankin Scale(m RS)at 30 days and 90 days after surgery.The time to emergence from general anaethesia was performed on the modified intention-totreat(m ITT),and the critical time of non-inferiority was 2.55 min,and its sensitivity analysis were performed on the per-protocol(PP)population and the intention-to-treat(ITT)population after multiple imputation based on demographic.Subgroup analysis was performed on the difference of the time to emergence between the two groups,and the factors prolongling the time to emergence were analyzed by Logistic regression.【Results】1)From July 2021 to June 2022,142 participants were ranbomised and 129 completed the study.The baseline data and surgical characteristics of patients was comparable in remimazolam and propofol groups.2)In terms of the primary outcome,in the m ITT population,the time to emergence from general anaethesia was 16.1±10.4min in group remimazolam and 19.0±11.2min in group propofol,the mean difference between the two groups was-2.9min(95% confidence interval:-6.5min to 0.7min).Because the 95% confidence interval did not cross the non-inferiority margin of 2.55(P=0.003 for non-inferiority),the time to emergence of remimazolam was confirmed to be noninferior.Results were consistent in the sensitivity analysis of the PP population and of the ITT population.3)In terms of the secondary outcome,the incidence of hypotension during induction was lower(11.3% vs.25.4%,P=0.030)and fewer patients needed vasopressors during surgery(29.6% vs.62.0%,P<0.001)in group remimazolam.The mean arterial pressure in group remimazolam was significantly higher than that in group propofol immediately before intubation(78.8±12.0mm Hg vs.73.1±11.2mm Hg,P=0.004)and immediately after intubation(113.8±23.0mm Hg vs.98.2±20.7mm Hg,P<0.001).The heart rate in group remimazolam was significantly higher than that in group propofol immediately before intubation(65.6±9.9bpm vs.60.9±9.3bpm,P=0.004),immediately after intubation(94.5±16.2bpm vs.81.0±18.3bpm,P<0.001)and at the beginning of operation(66.9±12.2bpm vs.58.6±9.2 bpm,P<0.001).Analysis of variance for repeated measurement showed significant inter-group,intra-group,and interaction effects in the difference of mean arterial pressure and heart rate betweent two groups(P<0.05).Compared with group propofol,the response time(13.6±6.1min vs.16.8±7.2min,P=0.004)and the recovery time of spontaneous breathing(15.6±7.2min vs.19.7±15.0min,P=0.040)were shorter in remimazolam after stopping drugs infusion.There was no statistical difference in other secondary outcomes,such as the incidence of POD and of major complications during postoperative hospitalization,and the m RS at 30 days and 90 days after surgery.4)Subgroup analysis showed that remimazolam significantly reduced the time to emergence compared with propofol for patients aged <65 years(P=0.020),the mean difference was-3.9min(95% confidence interval:-7.1min to-0.6min).Logistic regression showed that age ≥65 years was associated with prolonged time to emergence(P=0.014),odds ratio was 3.01(95% confidence interval: 1.25 to 7.25).【Conclusion】For patients undergoing cerebral endovascular procedures under general anesthesia,remimazolam is a safe and effective anesthetic that can replace propofol.Compared with propofol,remimazolam can provide more stable hemodynamics without prolonging the time to emergence. |
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