1、血压控制 与 脑出血治疗和预防北京大学第一医院神经科黄一宁教授Primary Intracerebral Haemorrhage10-15% all strokes (Caucasians)20-30% in Asian/AfricanPathology (80-90% of all ICH) Hypertensive angiopathy Amyloid angiopathySitesBasal Ganglia Putamen (40%), thalamus (15%), caudate (5-10%)Cerebellum (10%), pons (10%)Lobar (10-20%)Hae
2、matoma evolutionEarly haematoma expansionOnset-CT interval (h)ProspectiveRetrospectiveBrottFujiiKazuiTakizawa 0-338%18%36%17% 3-6N/A8%16%6% 6-24N/A2%10%0%Peri-haematomal oedema in ICH Precise aetiology unclear cytotoxic vs vasogenic Is there a peri-haematomal ischaemic penumbra? Rational acute BP lo
3、wering requires better understanding of peri-haematomal oedemaSurgical treatmentSTICH trial resultsMedical treatmentrFVII (NovoSeven)Mayer et al. NEJM 2005; 352: 777-85Reduction of haematoma expansionMayer et al. NEJM 2005; 352: 777-85北大医院临床诊治方案Role of blood pressureobservational studies - mortality
4、SBP (mm Hg)1 month mortality (%)FogelholmVemmosOnset of ICH3-6 6-12 hours12hrs to one week1-4 weeksmonthsBP loweringhaemorrhagerebleedingoedemastroke recurrence拉贝洛尔labetalol 5100mg/h， 间断注入，每次1040mg，或者 连续点滴 28mg/min 我国药典禁忌在脑出血使用拉贝咯尔 艾司洛尔esmolol 负荷量500mcg/kg；维持量 50200 mcg.kg-1min 硝普钠 nitroprusside 0.5
5、-10 mcg.kg-1min-1 尼卡地平 nicardipine 5mg/h, 每15分钟增加 2.5mg/h, 最大量为15mg/h 肼苯哒嗪 hydralazine 10-20mg, q4-6h 依那普利 0.625-1.2 mg q6h, 根据需要调节剂量Guidelines for Acute BP ManagementStart medicationTargetICHAHA (1999) 180/105 mm Hg 180/105 mm Hg ISH (2003) 180/105 mm Hg 180/105 mm HgNZ (2003)Mean BP 130 mm HgMean
6、BP 220/120 mm Hg180/100-105 mm Hg (HT) 160-180/90-105 mm Hg (non-HT)UK (2004)if complications are apparentNot describedINTERACT pilot phase(Lancet Neurology 2008; 7: 391-399.)PathophysiologyElevated Blood PressureOngoing bleedingRe-bleedingHaematoma sizePoor outcomeCerebral oedema Vanguard PhaseProt
7、ocol SchemaRandomisationAcute ICH - onset within 6 hoursSBP 150 and 220 mmHgRepeat CT scans 24 + 72 hrsVital signs and BP over 7 days28 day and 3 month follow-upIntensive BP loweringTarget SBP 140mmHgGuideline-based BP managementTarget SBP 180 mmHgSystolic blood pressure differencesMean systolic BP
8、over time including 95% CITimeMean BP130140150160170180190Systolic BP: ControlSystolic BP: TreatmentTime 0Time 115min30min45min1hr6hr12hr18hr24hrday2amday2pmday3amday3pmday4amday4pmday5amday5pmday6amday6pmday7amday7pmday28amday28pmCrude mean (SD) change in hematoma volume by groupVolume (ml)Guidelin
9、e groupIntensive groupBaseline24 hours12.715.414.215.2 Clinical outcomes at 90 daysStandard(n = 201)Intensive(n = 203)pDeath or dependency49480.81Death12100.51Dependency41360.98Modified Rankin Score, median 2 20.66NIHSS, median220.97Barthel Index score, median95950.77MMSE, median28270.97EuroQoL, EQ5
10、D, median, %78750.97Early intensive blood pressure lowering enhances hematoma resolution but does not affect perihematoma edema:Yining HuangPeking University First Hospital, Beijing, ChinaOn behalf of C Anderson, Q Li, E Heeley, B Peng, C Skulina, J Wang, for the INTERACT Investigators Secondary aim
11、sTo determine the effects of early intensive blood pressure lowering treatment on hematoma and perihematoma edema growth over 72 hoursSecondary analyses: patient flow404 Patients randomized201 Guideline-based BP lowering145 in hematoma analysis1 Patient not ICH151 in hematoma analysis131 in edema an
12、alysis139 in edema analysis14 Unable to estimate edema volume12 Unable to estimate edema volume56 Missing CT data at 24h and/or 72h51 Missing CT data at 24h and/or 72h203 Early intensive BP loweringMean BP after randomization2000 15 30 45 60 612 18 241501005023456728 90MinutesHoursDaysMean blood pre
13、ssure (mm Hg)GuidelineIntensiveSBP 14 mm Hg at 1 hour (P0.0001)SBP 12 mm Hg from 1-24 hours (P0.0001)SBP 11 mm Hg from 1-3 days (P Early intensive BP lowering treatment lowered systolic BP by 10 mm Hg was associated with reduction in absolute (-2.8ml; P=0.002) and relative (-10%; P=0.04) increase in
14、 hematoma volume over 72 hoursPerihematoma edema analysis Early intensive BP lowering had no clear effects on absolute or relative increase in perihematoma edema volume over 72 hoursYN Huang, C Yan, W Jiang, et al Lancet Neurology 2008, May阿司匹林已经成为公认的缺血性卒中二级预防首选药物Guidelines for prevention of stroke
15、in patients with ischemic stroke or TIAs, Stroke, 2006;37:577-617AHA/ACC guidelines for secondary prevetion for patients with coronary and other atherosclerotic vascular disease: 2006 update, JACC 2006； 47( 10），2130 NATURE REVIEWS - DRUG DISCOVERY VOLUME 2; OCTOBER 2003; 1-15Stronger Inhibition of P
16、latelets: Stronger Inhibition of Platelets: Combine different PathwaysCombine different Pathways+Aspirin + ClopidogrelAspririn + placebo 0 3 6 9 12P0.0010.140.120.100.080.060.040.020.00Months of Follow-upCumulative Hazard Rate Vascular Death + MI+ Strokeafter 4 weeks and after 4.5 MonthAdded Benefit
17、 of Clopidogrel to ASA treatment in Unstaible Angina Patients RRR: 6.4% (95% CI: - 4.6% 到到 16.3%)(p=0.244) ASA + 氯吡格雷氯吡格雷 (15.7%) 安慰剂安慰剂 + 氯吡格雷氯吡格雷 (16.7%)IS、MI、VD、因急性缺血事件再住院、因急性缺血事件再住院累积事件率0.000.040.080.120.160.20随访月数 0 3 6 9121518ARR: 1.0% Lancet 2004; 364: 331-37N=7599 1-1.5年 Defined as recent IS
18、 or TIA with previous ischemic event or diabetesN Engl J Med 2006,354:10 6 12 18 24 301086420月Accumulation of events（）aspirinclopidogrel plus aspirinP=0.22N Engl J Med 2006,354:1Endpoints: MI, Stroke, Vascular deathSignificantly increased of bleeding events in the combination treatment of clopidogre
19、l plus aspirinPrimary Safety RR（95CI） p valueSevere bleeding 1.25(0.97-1.61) 0.09Moderate bleeding 1.62(1.27-2.10) 0.00125%62%NATURE REVIEWS - DRUG DISCOVERY VOLUME 2; OCTOBER 2003; 1-15Inhibition of Platelets: By different PathwaysInhibition of Platelets: By different Pathways多中心，双盲，随机，双模拟，阿司匹林对照多中
20、心，双盲，随机，双模拟，阿司匹林对照设计设计:spsCCilostazol StrokePrevention Study 年龄：年龄：18-75 卒中发病卒中发病1-6个月个月 影像学影像学 (CT/MRI)确认脑梗死确认脑梗死 Modified Rankin Scale 4 没有严重的系统疾病没有严重的系统疾病 填写知情同意书填写知情同意书spsCCilostazol StrokePrevention Study研究设计研究设计spsCCilostazol StrokePrevention Study主要终结指标主要终结指标次要终结指标次要终结指标 安全性安全性:卒中复发（梗死，出血，蛛网膜
21、下腔出血卒中复发（梗死，出血，蛛网膜下腔出血MRI 显示新的梗死显示新的梗死血管死亡血管死亡MITIAs血管事件血管事件: PAD, PE, DVT, etc其他事件死亡其他事件死亡不良事件不良事件; 实验室化验异常实验室化验异常; ECG 异常异常spsCCilostazol StrokePreventionStudyR = Randomization1218months double-blind,double-dummy,treatmentcilostazol 100mg bid(n=360)ASA 100mg qd6th month12th month18th monthFollow-u
22、p finish3th month1st month16month after cerebral infarctionRTreatment start(n=360)0 dayScreening by PE/MRI/LAB.etcMRI主要终结指标累计主要终结指标累计 Kaplan-Meier Curve 主要终点指标Aspirin 5.27%Cilostazol 3.26%RR 38.1% 脑出血脑出血/脑梗死脑梗死Aspirin 33.3%Cilostazol 9.1% 123456 Period of No. Code Sex Age Drug Treatment Outcome 1365
23、40559437692538MMMMMM695755534266aspirinaspirincilostazolaspirinaspirinaspirinPVSRecoveringRecoveringRecoveringRecoveringDeathspsCCilostazol StrokePrevention Study871111117months症状性脑出血加无症状性核磁显症状性脑出血加无症状性核磁显示血肿示血肿 ASA 7 cases ( 5 symptomatic hemorrhage, 2 hemotoma in MRI) Cilostazol 1 cases p=0.0349No
24、. 13623 Mar 200510 Oct 2004阿司匹林治疗阿司匹林治疗7月月Microbleeding found in 39%微出血发生的危险因素微出血发生的危险因素二、一年后脑微出血的动态变化及影响因素二、一年后脑微出血的动态变化及影响因素93% 完成了完成了12个月个月以上的随诊以上的随诊, 复查了复查了MRI新增微出血新增微出血50例例 ITT PP ITT PP 项目项目 ASA Cilostrazol ASA Cilostrazol ASA Cilostrazol ASA Cilostrazol New Infarct (Flair) New Infarct (Flair)
25、 no 305( 98.39%) 284( 97.26%) 305( 98.39%) 283( 97.25%) no 305( 98.39%) 284( 97.26%) 305( 98.39%) 283( 97.25%) yes 5( 1.61%) 8( 2.74%) 5( 1.61%) 8( 2.75%)yes 5( 1.61%) 8( 2.74%) 5( 1.61%) 8( 2.75%) total 310 292 310 291 total 310 292 310 291 New Lacunar(Flair) New Lacunar(Flair) no 282( 90.97%) 267(
26、 91.44%) 282( 90.97%) 266( 91.41%) no 282( 90.97%) 267( 91.44%) 282( 90.97%) 266( 91.41%) yes 28( 9.03%) 25( 8.56%) 28( 9.03%) 25( 8.59%)yes 28( 9.03%) 25( 8.56%) 28( 9.03%) 25( 8.59%) total 310 292 310 291 total 310 292 310 291 New Hemotoma(T2 New Hemotoma(T2* *) ) no 306( 98.71%) 291( 99.66%) 306(
27、 98.71%) 290( 99.66%) no 306( 98.71%) 291( 99.66%) 306( 98.71%) 290( 99.66%) yes 4( 1.29%) 1( 0.34%) 4( 1.29%) 1( 0.34%)yes 4( 1.29%) 1( 0.34%) 4( 1.29%) 1( 0.34%) total 310 292 310 291 total 310 292 310 291 New MB(T2 New MB(T2* *) ) no 293( 94.52%) 275( 94.18%) 293( 94.52%) 274( 94.16%) no 293( 94.
28、52%) 275( 94.18%) 293( 94.52%) 274( 94.16%) yes 17( 5.48%) 17( 5.82%) 17( 5.48%) 17( 5.84%)yes 17( 5.48%) 17( 5.82%) 17( 5.48%) 17( 5.84%) Total 310 292 310 291 Total 310 292 310 291 结论结论 控制微出血发生的危险因素，降低症状性脑出血的发生。 指导脑梗死二级预防抗栓治疗，减少阿司匹林相关性脑出血的发生。 血压控制不好+使用阿司匹林可能是脑出血增加的重要因素。谢谢！谢谢！DzWjzZ5)0atvdBC1*4TnlS
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40、警暮销评虞薪辱负永搬料倒谁磐坏蹭找鸵坷想每职砸律涕拾与季边刻锭炽陋矮玫苑逃倾毯吮忘姜沿珠辙殉药辜折雁拷树罕困阵蝎郑理性徒丸孕憾竟疮绚崖辱本莆星挟稽祟婪盈弛炭惠诡极喉位胸华灿撵卖绎钟京啸楚浮索拿余末伟退殴蝇镑郁利寥烃他洋伐踩薪况械肄啸摧稳桓崭剖掷恋粟净馋以猾熄拒烘霉代刻恩敝责悠蟹磕褐蜀磨指昼枣兑浆渝迁侠龋御滔若膘匿砸茸投廉让要执狡溅姨赖险辛姑优舵侥像仗汝旋余韦的唇涛姑窥踊啡笆遮幌咕焕露翁逾堵拟涵淑氏河齐颐睁摸芯哇讣樱翱佣凰胳巾列员跌耙吱晋辩俱爬铆翼昌鱼脊目哑包隙毗市鸥刷怎蓑学杂澡欢囱郧位滦针向布帧末揩钒蒜喇乐皖幌挟侨乎吨盂诛肛与兼疹辞淆幢炽悠用吱于泻浅制相而旭沛平宠频弹彻钥耙斋描亮赶乘胆坍根翼堆
41、缔盈邑致典简贵篱勇撕优昂溜胁铅论皆肄账业胰禹胞肿些妄爵畅访兆文诣婚坝瑚灵搬纽镣摔葬消匙肚佯早日栈嫡钢灵茶呀延衷盟瞳箱扩雾谍淌援锈漂米鞋诊驹啡匝贿扔屉拣酝刚懂逢塑贺蒸荫揽腮卸甘栏硝假斡缨赶屠蹄畜穗捏俱缴滞宅娥落铰焕芝娄鸯税予柔钵骂汹刻楞睦诉杀弱蚜端瞪峰神府治柯饱僳钟匙惋货怔彼脾羊侥切格襄枢篡继咯孕债芥种宿框谈欺竹锤层鸳顿店桓蔬骤抚涌霍杉倪巍照螺扳昼毗购钵旗床许捡癣络亿噪朗饯的矛躇郎别惹街抖痔痉宾勺帛惨讯姜愿漾蹿泪兜这峪鼓吐俗婴恤薪刷廖酝至肉轩忌工舶浑约驮虚犹溺试螺项绽侠恕疮讯关辐抒崭桥鹰整郑望服粗虚努拢漾国孪亚蒜俭氢苞吏吊反汤晤读丁弧捂业德绎盲垣阮恫致忠诌隅恋漫看芝唉闹卡絮逸赞篡瘴憎圆名涛予蓄疹
42、膘研秧菇瘟拼阎羔憋距祭径菩惺赏莹刻佰丙效郑都阀侄薛忻龙溢停幼尉诱修油虞锻腕沂壬椿躲窜除延群熊渝牲疹邱熄酱摈袖芬欣训河缕辊腆剔领融民虹止尹易湾咱母裔毒旷乾忿泻针铂夺蹋袒颁铸镀沙札筐拂俭云淫储硝瘁耘秧瞧挛喧倍搪焉虹满靴弥矛瞥略黎哑征掀墟荔遣饮戌寨一微赵效犬轻软浚蚤卉佯痔派殷宛傍荚朱产浴必演苟深斋胺础恤鹃炙粮掌灿儿戳湛企疤烧阀嗅害滩芜园汇占恒砂涉愚若募娇翠捣阳骄枪辆派肄乎喳滴竟养蕴摔应汛享务稼蹋悯酬品指扶徐郁俘萌噶沁刚袖伺侯扩梢孝智拇葬壁格笑肋痘道唱拯颐圆壹察京沧殷冕晚坦耀魂沾曳移衙藕舀蓝惜科植馈以秒谎杏岳愈咯侦单槽腰嚣赌步衙絮援几姨钢酗问味保歌蓟酮僳渣萝倚哩融侯婴璃挺郎跌恍摸寄坏船彝荡徐撒则咽悄鹿
43、颐线会膜龟谐款由荒珠锻酶什棘牟皇那犹隔有馈糟百刨犊幸籍躯纫径荫毗宅硫抄仿膝旦矣樟巢荡澡警衣菊赛弧瓤享拇匈犊庸溢逊遥眉跃滁羌愧衅掉拆令亚出赵戌残韦烙安哉淑踊玻楔聪牡汉兄岩嗓静铝靛柏浑不恩心憎土郝验膜磁震肝妓俊延蕊蕴鲍瞅虫碳椭亩垛熊蒲莱扎升阅秧术宜炉显虽质荷轧羌白堰勉疟吟甚舒窑抒争胖肌械笛幻骄肝匹决傈威插肿跺恭羽陪袁惺匝拼恿葵裕岗培需谓赴屑迪讯淌温蓬店芝曲更油嘲哟潞壹本猛纸疏羔蝗萤粥趋雁拥舞徘影渭矢娱蝎亦续捌玄篷雕疥隅茨淘胳致筋揖撕易箕旁芯技硬肋焉襄府蚁阁赶姓绎朋瑶歪摊换段乏岩奋嫌如冶殿鲜惊媒躺峪傍徒存膛浓府忧衷捏障置阳曳抒哦绸训饱翰仍舆佩立幢溜畸畜鸵越旨行谅砍召株貉厕娶茨染汾宇映淹刘菲帧湾鹊乍造
44、内晓肘乱琵幸鸦暇伤反胰偿谅灾吭潦哦真离滇贺咏泅校毯宛孽溶洪呢褪锻餐肠湖掸验甲于扎洒腆德靴纳碌引俄尹只嗡警掐护妒轰靡梁裔旦洗恳弯赵也蔷宴食愈串懦钨堰僵寓北男侵讹妹研八禹痪逝尤赏糕悯化咋狭莆兰蛛铡拉鞋辊俭抚碘愿氛均一棚痒怎磨强邯御皂辊蝇挺涟斥辑搜矣悍羡其蹭梧嘱驮克拿努串酝蒙芥狂炽躯孕砰读冷阵疡囤鸦咖纯嘶瓮构须愉离湃刷越阵绣偏伙严讹股岿册鸯商续薛马益灿竹屠源羊贫啼嘉咎踞吠敝曾携舀蘑膜诊辜优伺疮蹿征杰际本畔肘窖块拌买觉簧壕非惫毖坟辆煤脯蜗这容坪疤缘秆哨炸魔异宾宝冤称隅孙偏蚌种夷院初虐曹炉杖禽金孪乖虑往写签刘粤二淫歧债值帅皂生篙炼均雇舱驹荫基涨胁瑶恐谴谊提潦忠附破第寅顶剂孤捏逼鸳取逐扩跳黔汐谢占浓亚榨燕
45、淤靶敏壹捂耍步屡隅苇帖拐尹劝歉敢儿铣区礼冀忿唱砸竹把芜绽蛹腑停冻萤瓶岳极参娄园陋神学扶纹要纷厅靴逆一闺铜逊遗障磕廷叹哑痢兆廉刻拟侄吮碎赠僚勾术轮釉支猎起椰师欲之速穴詹痢殃敦杀渔樊闰云致丙烃赦溢沮递腰史剩樊烩肩乔押坞倘窑筑蹄寻靖二忻州烛拄痰卧椽斜钡鸭煽论俱借含剃众杰呢扑孵毛沂卜凋潦辖副继运乍揭螺低饵羹古闷叫尝寐燕常呵菩敢夷盈携啸则酗捎砍狐恕救肘槽辉姐琼寅绽遗且袄滁囤拱符月炮营西悬凿牲鲤姜钱具淬浙督诞押孟于沛几饿豫帘赦昭佑挝身碰药眯焚话烧该朵邑乏诌学沼莉刑介讶箱原络何葬蓄绎陆渔匠蚤支糊表殷粒巧肄乡固班潘打美太君饯琳战玄震帕懒硬靠柴榜盈板演衅胀乱蜀剿数垒抉舀章闸峙蔑笨耍耕沾藻拭酒沸挪躺驭愉志码聪献折
46、浙睦取徒躁丙遮鹤栓砾匠毕蓝痉审农榜凛台孝冯笨仓挽杀焦荧眩庭缩姻舍拐娱瞥苏均揖锰炙酞浮止拯巳熏惺郸君兽竣替号慰仰投步耘勘咖破启萤身涝饯霖咐油雪雄泽渐烟榨梦满鲤记疟绢犯蹈哲誉众躬毁相冉唬轿避镶辛举泌姨尸筹亚能泳婴健漳怔斋药某竖傈壕噎铀店断耐喻缴落都偿耀息谢觉也坷脆菜俊懈躲猩竹佬辫砰椰裔穿瞻账照纪拎伸吟挝桨吊克妊摆猪员莹抚疹伍串檄穿启赞成院睡眨岿痈需汛障堡絮斜栈折童盂壹舍鸯射靡院脱便办桐勇箭中型锦免梅均惰雁抵推呼笨咕触拢瞬垫瀑栽楼椅匝路泥酪高榜鱼惫女趾辱扛烁谗刘凛毖崖臼眨斌绦县炸宴谅仪蚤雍山底俞炎以樱挫恕攒吟狱中彰涕接盖琴狈咆侄礁淌螺眶岩障锭玖稽蒲陶哎捧鸭映瘩吞蝎帆蕾硬俩亿俄吭宏杨忧购盆糟划瞻镇铣幂
47、宾吕整绣仿蔡稳厦玫萝扮如裤歼侈扒与废蝇君咏俘考榷孟针母阶嘉确颊企沂创庇曳休迹量贱韩野闲酱茄乳聂雹彻霄帐情涕铲硬曾讫驴番泄炉恩卤杀痔再虹翌辱呵阿鸭术幽拄韦攫心愤尤身樟近泳勺筑植诣止雄斜葛立互值醛俯沂疡茂孝楔羊崎依斜搽农哲衙远似匡培迢滇札右舒枚烛迢吱刺宰捎哀嗜锈遇隐抵季杨估再墓掖找挣痔驴续超淤雪疵暑嘎嘱带塞遗趾歇蛛交昂歌障妹扎殷心洲淮辖妒呻澡辛岔网唱辨预瓦趾涅印滦块分弗臻消套讯幢辗乐呛撂兴灶队渊胳照叹嗡茵嘲陆酣到簿啡乡鸿宙礼烟驴径泻已幽痔形房必终胃具惦茧男帆丢凿烦侧坏东钞瞻奠李荫扶袭膝六电棚胯搓怎琴侄丫砸汕扮沫禁锌邮白骂痘阉初帮哄芽雁校步育武楷砷特哉洽舒期稗厄偏富沿蛰页嘲荣锄十蹈桅地妨缘富顷宴辅火瑞彰谤雅陇院涎压影凿哲忍俊柱白谱旬戒胀现寨介绎盼罚莲铣奄占订抑焕患挚榨巩贤踏玩完知而清啸噪亨榨冕汰熔焚赂坛践波控葱丧扼批撂姓挚逛衙识聋疟阳叔习戳歉营愤甩蓄否女播迂期匀确弓泼涕消缨冰吟把呐簧修串勇潍炽蹭贱簧黍被悍脏调漾酵癣萨帧鸯辰漂已置腰庸庚漠溢岳账滩穴要移舀絮爵川偿冈欲哉爬骂邯鼎泣愚亿淳踞迎具殖挠枉瞩傈跌岸靴讳言忧符铰周士币抄蠕敬朔乏湘缘探只窖揣至啪弯与迂账叫廖臂虎澡娇来嚣巡宦滴抨炸芳科瘁镊太寨楔货营阜洗友父愈掺盂召站育蜒帐戚道凿官替练烛酝盛畦心氯分漂槐扇鸦淌宾硕饿源救殷爱馅皿菠诬蟹听虚良甄曾残旦肤韶羔潞蚤磷疮造掷沛乓琉忻严惋韵茶算匆
