远隔缺血后适应治疗对急性缺血性卒中超时间窗患者临床预后的影响:一项随机对照试验

Effect of the Remote Ischemic Postconditioning on the Prognosis of Patients with Acute Ischemic Stroke beyond Time Window:a Randomized Controlled Trial

背景急性缺血性卒中(AIS)高发,及时恢复脑血流是治疗的关键,超时间窗就诊患者无更多促进脑血流恢复的治疗手段。研究远隔缺血后适应(RIPostC)治疗对AIS超时间窗就诊患者的临床疗效、并发症和预后,具有重要的临床意义。目的探究RIPostC治疗对AIS超时间窗患者干预的影响,为超时间窗就诊的AIS患者寻求安全、有效的脑血流恢复治疗方式。方法本研究采用随机、分组、安慰剂对照法进行试验。选取2021-09-02—2022-08-31于北京航天总医院神经内科病房住院治疗的超溶栓时间窗(发病时间>6 h)的AIS患者为研究对象。依据随机数字表法将患者分为对照组和试验组。试验期+随访期共90 d,均使用同等的一般治疗、脑血管病常规治疗,试验组在此基础上给予RIPostC治疗14 d(28次),对照组给予模拟的RIPostC治疗14 d(28次)。在干预前和干预后30 d、干预后90 d,采用改良Rankin量表(mRS)、美国国立卫生研究院卒中量表(NIHSS)评估两组患者神经功能,简易精神状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)评估患者认知功能,工具性日常生活能力量表(IADL)评估日常生活能力,焦虑自评量表(SAS)、抑郁自评量表(SDS)评估精神状态,经颅多普勒超声(TCD)评估脑血流速度,以白介素(IL)-6反映炎症情况。结果122例患者中,最终完成试验及随访99例,其中试验组49例,对照组50例。两组患者性别、年龄、基础疾病(高血压、糖尿病、冠心病)及基线NIHSS评分比较,差异无统计学意义(P>0.05)。重复测量方差分析结果示,时间与组别对MMSE、MoCA、mRS、NIHSS、脑血流速度、IL-6存在交互作用(P<0.05),时间和组别对MMSE、MoCA、NIHSS、脑血流速度、IL-6主效应显著(P<0.05),时间对mRS、SAS、SDS、IADL主效应显著(P<0.05)。试验组干预后30、90 d MMSE、MoCA评分及脑血流速度均高于对照组,mRS、NIHSS评分均低于对照组(P<0.05);试验组干预后30、90 d SDS、IADL评分低于对照组(P<0.05);试验组干预后30 d SAS评分高于对照组,IL-6低于对照组(P<0.05)。99例患者中共有23例患者发生不良反应,其中试验组17例,对照组6例,两组皮肤瘀点、头晕、心慌、胸闷发生率比较,差异无统计学意义(P>0.05);对照组患者皮肤瘀斑发生率[4.00%(2/50)与12.24%(6/49)]、总不良反应发生率[12.00%(6/50)与34.69%(17/49)]低于试验组(P<0.05)。结论RIPostC治疗可降低AIS患者的炎症反应,对神经功能、认知功能抑郁情绪及颅内血流速度可起到积极的改善效果。

Background The incidence of acute ischemic stroke(AIS)remains high,and a timely restoration of cerebral blood flow is crucial for its prognosis.There are less therapeutic approaches to promote recovery of cerebral blood flow in AIS patients treated beyond a limited time window.The analysis of remote ischemic postconditioning(RIPostC)on the efficacy,complications and prognosis of AIS patients beyond the time window is of great significance.Objective To investigate the role of RIPostC on the prognosis of AIS beyond time window,thus providing a safe and effective cerebral blood flow restoration way for AIS beyond time window.Methods It was a randomized,parallel group,placebo-controlled trial involving AIS patients beyond time window(onset time>6 h)of thrombolysis who were hospitalized in the Department of Neurology,Beijing Aerospace General Hospital from September 2,2021 to August 31,2022.They were randomly assigned into the control group and experimental group,and treated and followed up for 90 days.General treatment and conventional treatment of cerebrovascular disease were performed in both groups.RIPostC and simulated RIPostC were respectively given 28 times within 14 days in the experimental group and control group,respectively.Before the intervention,and 30 days and 90 days after the intervention,neurological function was assessed using the modified Rankin Scale(mRS)and the National Institutes of Health Stroke Scale(NIHSS).Cognitive function was assessed by the Mini-mental Status Examination(MMSE)and Montreal Cognitive Assessment(MoCA).Daily living ability was assessed by the Instrumental Activity of Daily Living(IADL).Mental status was assessed by the Self-rating Anxiety Scale(SAS)and Self-rating Depression Scale(SDS).Cerebral blood flow velocity was assessed by the transcranial Doppler ultrasound(TCD).Inflammatory response was assessed by measuring interleukin 6(IL-6)levels.Results Ninety-nine out of 122 AIS patients finally completed the trial and follow-up,including 49 patients in the experimental group and 50 in the control group.There were no significant differences in gender,age,underlying diseases(hypertension,diabetes,coronary heart disease)and baseline NIHSS scores between the two groups(P>0.05).Repeated measures analysis of variance showed that there was an interaction between time and group on MMSE,MoCA,mRS,NIHSS,cerebral blood flow velocity,and IL-6(P<0.05).Specifically,the main effects of time and group on MMSE,MoCA,NIHSS,cerebral blood flow velocity,and IL-6 were significant(P<0.05),and the main effects of time on mRS,SAS,SDS,and IADL were significant(P<0.05).The MMSE and MoCA scores and cerebral blood flow velocity on 30 days and 90 days after the intervention were significantly higher in the experimental group than those of the control group,while the mRS and NIHSS scores were significantly lower(P<0.05).The SDS and IADL scores on 30,90 days after the intervention were significantly lower than those of control group(P<0.05).On 30 days after the intervention,AIS patients in the experimental group had significantly higher SAS score and lower IL-6 level than those of control group(P<0.05).Adverse events were reported in 23 AIS patients,including 17 in the experimental group and 6 in the control group.There was no significant difference in the incidence of skin petechiae,dizziness,palpitation,chest tightness between the two groups(P>0.05).The incidence of skin ecchymosis[4.00%(2/50)vs.12.24%(6/49)]and the overall incidence of adverse events[12.00%(6/50)vs.34.69%(17/49)]in the control group were significantly lower than those of the experimental group(P<0.05).Conclusion RIPostC can reduce the inflammatory response in AIS patients,and protect neurological function,cognitive function,depression and intracranial blood flow velocity.