血压控制 与 脑出血治疗和预防课件

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血压控制 与 脑出血治疗和预防北京大学第一医院神经科1Primary Intracerebral Haemorrhage10-15%all strokes(Caucasians)20-30%in Asian/AfricanPathology(80-90%of all ICH)Hypertensive angiopathyAmyloid angiopathySitesBasal GangliaPutamen(40%),thalamus(15%),caudate(5-10%)Cerebellum(10%),pons(10%)Lobar(10-20%)Primary Intracerebral Haemorrh2Haematoma evolutionHaematoma evolution3Early haematoma expansionOnset-CT interval(h)ProspectiveRetrospectiveBrottFujiiKazuiTakizawa 0-338%18%36%17%3-6N/A8%16%6%6-24N/A2%10%0%Early haematoma expansionProsp4Peri-haematomal oedema in ICHPrecise aetiology unclearcytotoxic vs vasogenicIs there a peri-haematomal ischaemic penumbra?Rational acute BP lowering requires better understanding of peri-haematomal oedemaPeri-haematomal oedema in ICHP5Surgical treatmentSTICH trial resultsSurgical treatmentSTICH trial6Medical treatmentrFVII(NovoSeven)Mayer et al.NEJM 2005;352:777-85Medical treatmentrFVII(NovoS7Reduction of haematoma expansionMayer et al.NEJM 2005;352:777-85Reduction of haematoma expansi8北大医院临床诊治方案北大医院临床诊治方案9n n平扫CT应该作为首选，对脑出血和蛛网膜下腔出血均很敏感。n n核磁对可疑的脑出血诊断和处理上也很有帮助。脑出血包括硬膜外和硬膜下出血、蛛网膜下腔出血、脑室出血、梗塞后出血以及脑实质出血。n n一定要考虑到：凝血疾病、外伤、血管损伤、静脉血栓形成，以及动脉瘤破裂。平扫CT应该作为首选，对脑出血和蛛网膜下腔出血均很敏感。1010下述步骤应该是同步进行下述步骤应该是同步进行n n评估生命体症：判断患者做影像学检查时是否能忍受，是否要插管。n n若认为需要插管，可以使用超短作用的神经肌肉阻断剂或者镇静剂，避免长时间影响观察患者运动功能和神经功能。n n对于血压严重升高的患者应该评估是否有心肌的损伤。下述步骤应该是同步进行评估生命体症：判断患者做影像学检查时1111n n血液检查：血液检查：PTPT、INRINR、PTTPTT、血小板计数和全血计、血小板计数和全血计数、数、D DDimerDimer、纤维蛋白原、电解质、纤维蛋白原、电解质、BUNBUN、CrCr、血糖、肝功能、血型。血糖、肝功能、血型。n n需要与神经外科联系：需要与神经外科联系：n n小脑出血时神经外科急症；小脑出血时神经外科急症；n n非优势半球的脑叶出血，临床神经功能进行性加重；非优势半球的脑叶出血，临床神经功能进行性加重；n n对于特殊患者，如年轻患者、优势半球不清楚，等情对于特殊患者，如年轻患者、优势半球不清楚，等情况下，考虑需要减压术者。况下，考虑需要减压术者。血液检查：PT、INR、PTT、血小板计数和全血计数、DD1212根据指南控制血压。n n所有需要连续静脉降压的患者，都应该急诊放置动脉导管，监测血压和中心静脉压，同时使用静脉降压药。n n一旦决定药静脉降压治疗，必须指定专人床旁监测血压和治疗效果，直至血压得到控制。根据指南控制血压。所有需要连续静脉降压的患者，都应该急诊放置1313Role of blood pressureobservational studies-mortalityadmission BP and mortalitySBP(mm Hg)1 month mortality(%)FogelholmVemmosRole of blood pressureadmissio1414Onset of ICH3-6 6-12 hours12hrs to one week1-4 weeksmonthsBP loweringhaemorrhagerebleedingoedemastroke recurrenceBP loweringPotential therapeutic mechanismsOnset of ICH3-6 6-1212hrs t1515脑出血患者血压控制方案拉贝洛尔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 0.5-10 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,根据需要调节剂量脑出血患者血压控制方案1616Guidelines 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 BP 220/120 mm Hg180/100-105 mm Hg(HT)160-180/90-105 mm Hg(non-HT)UK(2004)if complications are apparentNot describedGuidelines for Acute BP Manage17对于脑出血早期几个小时内可以根据下述步骤对于脑出血早期几个小时内可以根据下述步骤：n n收缩压收缩压 230mmHg 230mmHg，或者舒张压或者舒张压 140mmHg 140mmHg，间隔，间隔5 5分分钟测量钟测量2 2次血压，开始使用硝普钠次血压，开始使用硝普钠n n收缩压收缩压 180 180230 mmHg230 mmHg，舒张压舒张压 105 105140mmHg140mmHg，或，或者平均动脉压者平均动脉压 130 mmHg 130 mmHg，间隔间隔2020分钟测量分钟测量2 2次，开始次，开始静脉使用拉贝洛尔、艾司洛尔、依那普利，避免口服或舌静脉使用拉贝洛尔、艾司洛尔、依那普利，避免口服或舌下含服硝苯地平。下含服硝苯地平。n n收缩压收缩压180mmHg 180mmHg 舒张压舒张压105mmHg70mmHg70mmHg。n n当怀疑由于降低血压引起临床症状恶化，应考虑调整血压。当怀疑由于降低血压引起临床症状恶化，应考虑调整血压。对于脑出血早期几个小时内可以根据下述步骤：收缩压 230m1818问题n n什么时候降血压n n降到多少合适n n降压速度问题什么时候降血压1919INTERACT pilot phase(Lancet Neurology 2008;7:391-399.)INTERACT pilot phase(Lancet N20PathophysiologyElevated Blood PressureOngoing bleedingRe-bleedingHaematoma sizePoor outcomeCerebral oedemaPathophysiologyElevated Blood 21 Vanguard PhaseProtocol 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 mmHg Vanguard PhaseProtocol Schem22Systolic blood pressure differencesSystolic blood pressure differ23Crude mean(SD)change in hematoma volume by groupVolume(ml)Guideline groupIntensive groupBaseline24 hours12.715.414.215.2Crude mean(SD)change in hema24 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,EQ5D,median,%78750.97 Clinical outcomes at 90 daysS25Early 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 Early intensive blood pressureSecondary aimsTo determine the effects of early intensive blood pressure lowering treatment on hematoma and perihematoma edema growth over 72 hoursSecondary aimsTo determine th27血压控制 与 脑出血治疗和预防课件28Secondary analyses:patient flow404 Patients randomized201 Guideline-based BP lowering145 in hematoma analysis1 Patient not ICH151 in hematoma analysis131 in edema analysis139 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 loweringSecondary analyses:patient fl29Mean BP after randomization2000 15 30 45 60 612 18 241501005023456728 90MinutesHoursDaysMean blood pressure(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(PEarly 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 hematoma volume over 72 hoursPerihematoma edema analysisEarly intensive BP lowering had no clear effects on absolute or relative increase in perihematoma edema volume over 72 hoursSummary of resultsHematoma ana33Cilostazol v.s.Aspirin in Secondary Stroke PreventionYN Huang,C Yan,W Jiang,et al Lancet Neurology 2008,MayCilostazol v.s.Aspirin in Sec34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 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 阿司匹林已经成为公认的缺血性卒中二级预防首选药物35血压控制 与 脑出血治疗和预防课件36NATURE REVIEWS-DRUG DISCOVERY VOLUME 2;OCTOBER 2003;1-15Stronger Inhibition of Platelets:Combine different Pathways+NATURE REVIEWS-DRUG DISCOVER3737积极抗血小板治疗对不稳定性心绞痛作用只积极抗血小板治疗对不稳定性心绞痛作用只积极抗血小板治疗对不稳定性心绞痛作用只积极抗血小板治疗对不稳定性心绞痛作用只有在最初的几个星期明显有在最初的几个星期明显有在最初的几个星期明显有在最初的几个星期明显(CURE)(CURE)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 of Clopidogrel to ASA treatment in Unstaible Angina Patients 积极抗血小板治疗对不稳定性心绞痛作用只有在最初的几个星期明显3838 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 9121518氯吡格雷在近期短暂脑缺血发作或缺血性卒中氯吡格雷在近期短暂脑缺血发作或缺血性卒中氯吡格雷在近期短暂脑缺血发作或缺血性卒中氯吡格雷在近期短暂脑缺血发作或缺血性卒中的高危患者中对动的高危患者中对动的高危患者中对动的高危患者中对动脉粥样硬化血栓形成的处理脉粥样硬化血栓形成的处理脉粥样硬化血栓形成的处理脉粥样硬化血栓形成的处理（MATCHMATCH）：）：ARR:1.0%Lancet 2004;364:331-37N=7599 1-1.5年 RRR:6.4%ASA+氯吡格雷(13939增加增加ASA，并为给高危的脑血管病患者并为给高危的脑血管病患者病人带来额外的临床益处病人带来额外的临床益处l lMATCHMATCH研究显示，研究显示，对高危的缺血性脑血管病患者，对高危的缺血性脑血管病患者，在氯吡格雷标准治疗的基础上增加阿司匹林，阿司在氯吡格雷标准治疗的基础上增加阿司匹林，阿司匹林没有带来更多的临床益处匹林没有带来更多的临床益处(疗效疗效/风险比风险比)l l增加增加ASAASA导致更多的威胁生命的出血事件，主要是导致更多的威胁生命的出血事件，主要是胃肠道出血和颅内出血。胃肠道出血和颅内出血。Defined as recent IS or TIA with previous ischemic event or diabetes增加ASA，并为给高危的脑血管病患者病人带来额外的临床益处M4040Clopidogrel for High Atherothrombotic Risk and Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization,Management and Ischemic Stabilization,Management and AvoidanceAvoidance(CHARISMA)(CHARISMA)氯吡格雷用于动脉粥样硬化血栓形成高危及稳定、处理和避免缺血N Engl J Med 2006,354:1Clopidogrel for High Atherothr41410 6 12 18 24 301086420月Accumulation of events（）aspirinclopidogrel plus aspirinP=0.22N Engl J Med 2006,354:1Endpoints:MI,Stroke,Vascular death0 6 12 4242Significantly increased of bleeding events in the combination treatment of clopidogrel 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%CHARISMASignificantly increase4343ProfessProfess4444血压控制 与 脑出血治疗和预防课件4545血压控制 与 脑出血治疗和预防课件4646血压控制 与 脑出血治疗和预防课件4747NATURE REVIEWS-DRUG DISCOVERY VOLUME 2;OCTOBER 2003;1-15Inhibition of Platelets:By different PathwaysNATURE REVIEWS-DRUG DISCOVER48多中心，双盲，随机，双模拟，阿司匹林对照多中心，双盲，随机，双模拟，阿司匹林对照设计设计:spsCCilostazol StrokePrevention StudyCSPSTrial多中心，双盲，随机，双模拟，阿司匹林对照设计:spsCCil49入组标准入组标准年龄：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入组标准年龄：18-75spsCCilostazol Str50研究设计研究设计spsCCilostazol StrokePrevention Study主要主要终结指指标次要次要终结指指标 安全性安全性:卒中复卒中复发（梗死，出血，蛛网膜下腔出血（梗死，出血，蛛网膜下腔出血MRI 显示新的梗死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;实验室化室化验异常异常;ECG 异常异常研究设计spsCCilostazol Stroke主要终结指51设计流程设计流程spsCCilostazol StrokePreventionStudyR=Randomization1218months double-blind,double-dummy,treatmentcilostazol 100mg bid(n=360)ASA 100mg qd6th month12th month18th monthFollow-up finish3th month1st month16month after cerebral infarctionRTreatment start(n=360)0 dayScreening by PE/MRI/LAB.etcMRI设计流程spsCCilostazol StrokeR=R52主要终结指标累计主要终结指标累计 Kaplan-Meier Curve主要终结指标累计 Kaplan-Meier Curve53终结分析终结分析主要终点指标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%终结分析主要终点指标脑出血/脑梗死54脑出血患者脑出血患者123456 Period of No.Code Sex Age Drug Treatment Outcome 136540559437692538MMMMMM695755534266aspirinaspirincilostazolaspirinaspirinaspirinPVSRecoveringRecoveringRecoveringRecoveringDeathspsCCilostazol StrokePrevention Study871111117months脑出血患者1 55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=0.0349症状性脑出血加无症状性核磁显示血肿ASA 56No.13623 Mar 200510 Oct 2004阿司匹林治疗阿司匹林治疗7月月No.13623 Mar 200510 Oct 2004阿57Microbleeding found in 39%Microbleeding found in 39%58微出血发生的危险因素微出血发生的危险因素微出血发生的危险因素59二、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例例二、一年后脑微出血的动态变化及影响因素新增微出血50例60New lesions found in Second MRI ITT PPITT PP 项目项目 ASAASA Cilostrazol ASACilostrazol ASA CilostrazolCilostrazol New Infarct(Flair)New Infarct(Flair)no no 305(98.39%)284(97.26%)305(98.39%)283(97.25%)305(98.39%)284(97.26%)305(98.39%)283(97.25%)yesyes 5(1.61%)8(2.74%)5(1.61%)8(2.75%)5(1.61%)8(2.74%)5(1.61%)8(2.75%)total total 310 292 310 291310 292 310 291 New Lacunar(Flair)New Lacunar(Flair)no no 282(90.97%)267(91.44%)282(90.97%)266(91.41%)282(90.97%)267(91.44%)282(90.97%)266(91.41%)yesyes 28(9.03%)25(8.56%)28(9.03%)25(8.59%)28(9.03%)25(8.56%)28(9.03%)25(8.59%)total total 310 292 310 291310 292 310 291 New Hemotoma(T2*)New Hemotoma(T2*)no no 306(98.71%)291(99.66%)306(98.71%)290(99.66%)306(98.71%)291(99.66%)306(98.71%)290(99.66%)yesyes 4(1.29%)1(0.34%)4(1.29%)1(0.34%)4(1.29%)1(0.34%)4(1.29%)1(0.34%)total total 310 292 310 291310 292 310 291 New MB(T2*)New MB(T2*)no no 293(94.52%)275(94.18%)293(94.52%)274(94.16%)293(94.52%)275(94.18%)293(94.52%)274(94.16%)yesyes 17(5.48%)17(5.82%)17(5.48%)17(5.84%)17(5.48%)17(5.82%)17(5.48%)17(5.84%)Total Total 310 292 310 291310 292 310 291 New lesions found in Second MR61血压控制 与 脑出血治疗和预防课件62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。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。63谢谢！谢谢！谢谢！64