,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Company name,*,Click to edit Master title style,急性缺血性脑卒中静脉溶栓进展及经验分享,Company name,内 容,静脉溶栓理论依据,国内外静脉溶栓最新指南,溶栓的安全性评价,我院静脉溶栓经验,Company name,我国脑卒中超越恶性肿瘤跃居死因顺位首位,陈竺,.,中华人民共和国卫生部,.,全国第三次死因回顾抽样调查报告,.2006.09,脑血管病,恶性肿瘤,呼吸系统疾病,心血管病,损伤和中毒,单位：,1/10,万,Company name,早期再灌注治疗是缺血性脑卒中救治的关键,缺血半暗带,(,可逆性脑损伤,),1.Gonzlez RG.AJNR Am J Neuroradiol.2006 Apr;27(4):728-35.,2.Saver JF.Stroke 2006;37:263-266.,未治疗的缺血性脑卒中患者，缺血区每分钟将有,190,万,个神经元死亡,早期溶栓再灌注治疗，有利于挽救可逆性脑损伤,缺血中心区,(,不可逆性脑损伤,),Company name,如何尽早实现缺血性卒中再灌注？,缺血再灌注,静脉溶栓,血管内治疗,动脉溶栓,Company name,新英格兰医学杂志同期发表,IMS-III,IV r-tPA,联合血管内治疗,VS IV r-tPA,SYNTHESIS EXPANSION,血管内治疗,VS IV r-tPA,MR RESCUE,多模式影像筛选下,血管内治疗,VS IV r-tPA,N Engl J Med.2013 Jun 20;368(25):2430-35,Company name,急性缺血性卒中治疗建议流程,Company name,r-tPA:,国内外指南一致推荐的特异性溶栓药物,1.,Adams HP Jr,et al.,Circulation.2007 May 22;115(20):e478-534.,2.Del Zoppo GJ,et al.Stroke.2009 Aug;40:2945,2948.,3.,中华医学会神经病学分会脑血管病学组急性缺血性脑卒中诊治指南撰写组,.,中华神经科杂志,.2010;43(2):146-153.,4.European Stroke Organization(ESO).ESO GC Statement on revised guidelines for intravenous thrombolysis.,http:/www.eso-stroke.org/pdf/ESO_Guideline_Update_Jan_2009.pdf.,AHA/ASA,指南：,对符合适应症的缺血性脑卒中患者，推荐发病,3h,内给予,rt-PA,溶栓治疗,(,级推荐，,A,级证据,),中华医学会指南：,对缺血性脑卒中发病,3h,内的患者，应根据适应症严格筛选，尽快静脉给予,rt-PA,溶栓治疗,(,级推荐，,A,级证据,),ESO,指南：,推荐缺血性脑卒中发病,3h,内给予,rt-PA,溶栓治疗,(,级推荐，,A,级证据,),Company name,NINDS,(,美国）,1995,2008,ECASS,(,欧洲,),ECASS II,(,欧洲,/,大洋洲,),ATLANTIS,2005,SITS-MOST,(,欧盟,),2007,ECASS III,1996,1997,1998,1999,2000,2001,2002,2003,2004,2006,美国,FDA,批准,加拿大批准,德国批准,全欧洲,EMEA,批准,STARS,(,美国,),CASES,(,加拿大,),Pool analysis of NINDS/ECASS/ATLANTIS,Review of Thrombolysis for AIS,EPITHET,SITS-ISTR,r-tPA,审批使用历史,IST-3,Company name,Global outcome(mRS 0,1,Barthel Index 95,100,NIHSS 0,1)day 90,adjusted odds ratio with 95%confidence interval,n=2775,Hacke et al.,Lancet,.,2004;363(9411):768774.,2004,年,Combined,Analysis:,NINDS,ECASS I+II,ATLANTIS,Time Interval(OTT)min,Adjusted odds ratio,1.5h,OR 2.8*,3h,OR 1.5*,4.5h,OR 1.4*,6h,OR,“,1.2”,0.0,0.5,1.0,1.5,2.0,2.5,3.0,3.5,4.0,60,120,180,240,300,360,Company name,2012,年荟萃分析证实：,卒中发病,3h,内接受,r-tPA,溶栓治疗，获益最大,荟萃分析,NINDS,、,ECASS,、,ATLANTIS,、,IST-3,等,12,项研究，共纳入,7012,例患者，结果证实：,3h,内溶栓获益,(mRS 0-2),最大，进一步证明了缺血性卒中患者应尽早溶栓,Wardl aw JM,et al.,Lancet.2012 Jun 23;379(9834):2364-72.,mRS 0-2,的患者例数,/,总人数,(n),OR(95%CI),p,值,rt-PA,组,对照组,3h,365/896(41%),280/883(32%),1.53(1.26-1.86),p4.5h,，危害,获益（,FDA,批准,3h,）。,年龄：,80,岁，溶栓获益差于,80,岁，但较不溶栓效果好；获益主要来自,3h,内溶栓患者。（,IST-3,）,合并房颤：各大研究均未将房颤作为排除标准，房颤不是颅内出血的独立危险因素。,IST-3,房颤占,30%,，溶栓后获益不差于无房颤者。,抗凝,/,抗血小板治疗：抗血小板治疗不是排除标准；发病时口服抗凝剂，,INR1.7,患者，,3h,内溶栓不增加出血风险（过去认为发病,48h,内使用抗凝剂，,APTT,延长为排除标准）,中华内科杂志，,2012,51(12):1006-1009,JAMA.2012,307(24):2600-08,Company name,2012,年国内静脉溶栓最新专家共识,(,三,),特殊情况的溶栓治疗,轻症卒中：轻症或症状快速改善卒中不接受溶栓,1/3,将出现加重。研究认为，,NIHSS20,分，溶栓依然获益，不差于,80.,Severe stroke NIHSS 25.,Taking oral anticoagulant regardless INR.,History of DM and prior stroke.,Company name,IA Thrombolysis (I),Class I recommendation,Intra-arterial thrombolysis is an option for patients who have major stroke 6 hours durations due to the occlusion of MCA,otherwise not candidate for IV rtPA(Class I,Level of Evidence B).,Treatment requires the patients to be at an experienced stroke center with immediate access to cerebral angiography and qualified interventionalists.,The dosage is not established and the procedure has not been approved by FDA(Revised-NEW).,Company name,IA Thrombolysis (II),Class II recommendation:,IA thrombolysis is reasonable in patients who have contraindication for IV thrombolysis,such as recent surgery(Class IIa,Level of Evidence C),Class III recommendation:,The availability of IA thrombolysis should not generally preclude the IV rtPA in otherwise eligible patients(Class III,Evidence C),Company name,Endovascular Interventions,There are 4 FDA approved devices:Merci Retrieval System(2004),Penumbra System(2007),Solitaire Flow Restoration Device(2012),and Trevo Retriever(2012).,Regarding the effectiveness:Solitaire FR device and Trevo Retriever are better the Merci System(Class I,Evidence A,NEW),Company name,静脉溶栓的安全性评价,溶栓的绝对禁忌症,溶栓前评价,影响溶栓后病情进展的因素,溶栓后可能发生出血的临床及影像评价,溶栓后出血的治疗,Company name,溶栓的绝对禁忌症,不是卒中（低血糖、肿瘤）,CT,显示出血,大面积脑梗死（,ASPECT70ml,）,活动性大出血,近期不能压迫部位的外科手术,抗凝达标（,INR=2-3,）,Company name,急性缺血性脑卒中溶栓前评价,时间窗,是否溶栓绝对禁忌症,脑缺血的靶血管情况（,MRA,）,核心坏死区范围大小（,DWI,）,濒死的组织大小（,PWI/DWI/NIHSS,）,侧枝循环情况,是否存在影响血管开通后的全身或局部风险,患者及家属的价值取向,Company name,影响溶栓后症状波动或加重的因素,Company name,溶栓后出血的定义及分类,溶栓后出血分类：无症状性，症状性,症状性出血的定义：,-NINDS,定义：出血伴治疗后,36,小时内,NIHSS,恶化,1,-ECASS,定义：治疗后出现的任何一种颅内出血，且,NIHSS,较基线或,7,天内的最低值恶化,4,，或导致死亡。,-SITS-MOST,定义：治疗后,22-36,小时内，,PH2,型出血伴,NIHSS,恶化,4,或死亡。,Company name,急性缺血性卒中溶栓后出血转化的危险因素,临床因素,生化标记物,影像学改变,溶栓剂,(,剂量、用药途径、,时间窗,、不同的溶栓剂,),血糖升高（,200mg/dl,出血达,25%,）,CT,上早期缺血改变,卒中严重度,（,NIHSS,每提高,1,分，出血危险增加,1.38,倍）,红细胞增多,基线,CT,上,大面积梗塞,、水肿、占位效应,年龄,基质金属蛋白酶升高（破坏,BBB,）,腔梗的存在,糖尿病史,钙结合蛋白升高,PWI,上血流灌注少,血压高（,185/110mmHg,）,早期纤维蛋白原降解凝血病,血脑屏障破坏,心衰史,MRI,上有微出血或白质疏松,Company name,预测溶栓后出血的方法,一、出血发生率：平均,7.3%,NINDS,：,6.4%vs 0.6%,ECASS III,：,2.4%vs