血壓控制與腦出血治療和預(yù)防-醫(yī)學(xué)教學(xué)課件

1、血壓控制 與 腦出血治療和預(yù)防北京大學(xué)第一醫(yī)院神經(jīng)科黃一寧教授ynhuangPrimary 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%

2、)Haematoma evolutionEarly haematoma expansionPeri-haematomal oedema in ICHPrecise aetiology unclearcytotoxic vs vasogenicIs there a peri-haematomal ischaemic penumbra?Rational acute BP lowering requires better understanding of peri-haematomal oedemaSurgical treatmentSTICH trial resultsMedical treatm

3、entrFVII (NovoSeven)Mayer et al. NEJM 2005; 352: 777-85平掃CT應(yīng)該作為首選，對腦出血和蛛網(wǎng)膜下腔出血均很敏感。核磁對可疑的腦出血診斷和處理上也很有幫助。腦出血包括硬膜外和硬膜下出血、蛛網(wǎng)膜下腔出血、腦室出血、梗塞后出血以及腦實質(zhì)出血。一定要考慮到：凝血疾病、外傷、血管損傷、靜脈血栓形成，以及動脈瘤破裂。下述步驟應(yīng)該是同步進行評估生命體癥：判斷患者做影像學(xué)檢查時是否能忍受，是否要插管。若認(rèn)為需要插管，可以使用超短作用的神經(jīng)肌肉阻斷劑或者鎮(zhèn)靜劑，避免長時間影響觀察患者運動功能和神經(jīng)功能。對于血壓嚴(yán)重升高的患者應(yīng)該評估是否有心肌的損傷。血液檢查

4、：PT、INR、PTT、血小板計數(shù)和全血計數(shù)、DDimer、纖維蛋白原、電解質(zhì)、BUN、Cr、血糖、肝功能、血型。需要與神經(jīng)外科聯(lián)系：小腦出血時神經(jīng)外科急癥；非優(yōu)勢半球的腦葉出血，臨床神經(jīng)功能進行性加重；對于特殊患者，如年輕患者、優(yōu)勢半球不清楚，等情況下，考慮需要減壓術(shù)者。腦出血患者血壓控制方案拉貝洛爾labetalol 5100mg/h， 間斷注入，每次1040mg，或者 連續(xù)點滴 28mg/min 我國藥典禁忌在腦出血使用拉貝咯爾 艾司洛爾esmolol 負(fù)荷量500mcg/kg；維持量 50200 mcg.kg-1min 硝普鈉 nitroprusside 0.5-10 mcg.kg-1

5、min-1 尼卡地平 nicardipine 5mg/h, 每15分鐘增加 2.5mg/h, 最大量為15mg/h 肼苯噠嗪 hydralazine 10-20mg, q4-6h 依那普利 0.625-1.2 mg q6h, 根據(jù)需要調(diào)節(jié)劑量Guidelines for Acute BP Management對于腦出血早期幾個小時內(nèi)可以根據(jù)下述步驟：收縮壓 230mmHg， 或者舒張壓 140mmHg，間隔5分鐘測量2次血壓，開始使用硝普鈉收縮壓 180230 mmHg， 舒張壓 105140mmHg，或者平均動脈壓 130 mmHg， 間隔20分鐘測量2次，開始靜脈使用拉貝洛爾、艾司洛爾、依

6、那普利，避免口服或舌下含服硝苯地平。收縮壓180mmHg 舒張壓70mmHg。當(dāng)懷疑由于降低血壓引起臨床癥狀惡化，應(yīng)考慮調(diào)整血壓。問題什么時候降血壓降到多少合適降壓速度PathophysiologyElevated Blood PressureOngoing bleedingRe-bleedingHaematoma sizePoor outcomeCerebral oedema Vanguard PhaseProtocol SchemaRandomisationAcute ICH - onset within 6 hoursSBP 150 and 220 mmHgRepeat CT scans

7、 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 differencesCrude mean (SD) change in hematoma volume by groupVolume (ml)Guideline groupIntensive groupBaseline24 hours1

8、2.715.414.215.2 Clinical outcomes at 90 daysEarly 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 Inv

9、estigators Secondary aimsTo 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

10、 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 loweringMean BP after randomization2000153045606121824150100502345672890MinutesHoursDa

11、ysMean 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 (P10 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 ede

12、ma analysisEarly intensive BP lowering had no clear effects on absolute or relative increase in perihematoma edema volume over 72 hoursCilostazol v.s. Aspirin in Secondary Stroke PreventionYN Huang, C Yan, W Jiang, et al Lancet Neurology 2008, May阿司匹林已經(jīng)成為公認(rèn)的缺血性卒中二級預(yù)防首選藥物Guidelines for prevention of

13、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 NATURE REVIEWS - DRUG DISCOVERY VOLUME 2; OCTOBER 2003; 1-15Stronger Inhibiti

14、on of Platelets: Combine different Pathways+積極抗血小板治療對不穩(wěn)定性心絞痛作用只有在最初的幾個星期明顯 (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

15、to ASA treatment in Unstaible Angina Patients RRR: 6.4% (95% CI: - 4.6% 到 16.3%)(p=0.244) ASA + 氯吡格雷 (15.7%) 安慰劑 + 氯吡格雷 (16.7%)IS、MI、VD、因急性缺血事件再住院累積事件率0.000.040.080.120.160.20隨訪月數(shù) 0 3 6 9121518氯吡格雷在近期短暫腦缺血發(fā)作或缺血性卒中的高?；颊咧袑用}粥樣硬化血栓形成的處理（MATCH）： ARR: 1.0% Lancet 2004; 364: 331-37N=7599 1-1.5年增加ASA，并為給高危

16、的腦血管病患者病人帶來額外的臨床益處MATCH研究顯示，對高危的缺血性腦血管病患者，在氯吡格雷標(biāo)準(zhǔn)治療的基礎(chǔ)上增加阿司匹林，阿司匹林沒有帶來更多的臨床益處(療效/風(fēng)險比)增加ASA導(dǎo)致更多的威脅生命的出血事件，主要是胃腸道出血和顱內(nèi)出血。 Defined as recent IS or TIA with previous ischemic event or diabetesClopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance(CHARISMA)氯吡格雷用于動

17、脈粥樣硬化血栓形成高危及穩(wěn)定、處理和避免缺血N Engl J Med 2006,354:10 6 12 18 24 301086420月Accumulation of events（）aspirinclopidogrel plus aspirinP=0.22CHARISMAN Engl J Med 2006,354:1Endpoints: MI, Stroke, Vascular deathCHARISMASignificantly increased of bleeding events in the combination treatment of clopidogrel plus asp

18、irinPrimary Safety RR（95CI） p valueSevere bleeding 1.25(0.97-1.61) 0.09Moderate bleeding 1.62(1.27-2.10) 0.00125%62%ProfessNATURE REVIEWS - DRUG DISCOVERY VOLUME 2; OCTOBER 2003; 1-15Inhibition of Platelets: By different Pathways多中心，雙盲，隨機，雙模擬，阿司匹林對照設(shè)計:spsCCilostazol StrokePrevention StudyCSPS Trial入

19、組標(biāo)準(zhǔn)年齡：18-75卒中發(fā)病1-6個月 影像學(xué) (CT/MRI)確認(rèn)腦梗死 Modified Rankin Scale 4 沒有嚴(yán)重的系統(tǒng)疾病 填寫知情同意書spsCCilostazol StrokePrevention Study研究設(shè)計spsCCilostazol StrokePrevention Study主要終結(jié)指標(biāo)次要終結(jié)指標(biāo) 安全性:卒中復(fù)發(fā)（梗死，出血，蛛網(wǎng)膜下腔出血MRI 顯示新的梗死血管死亡MITIAs血管事件: PAD, PE, DVT, etc其他事件死亡不良事件; 實驗室化驗異常; ECG 異常設(shè)計流程spsCCilostazol StrokePreventionSt

20、udyR = 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主要終結(jié)指標(biāo)累計 Kaplan-Meier Curve終結(jié)分析主要終點指標(biāo)Aspi

21、rin 5.27%Cilostazol 3.26%RR 38.1% 腦出血/腦梗死Aspirin 33.3%Cilostazol 9.1% 腦出血患者123456 Period of No. Code Sex Age Drug Treatment Outcome 136540559437692538MMMMMM695755534266aspirinaspirincilostazolaspirinaspirinaspirinPVSRecoveringRecoveringRecoveringRecoveringDeathspsCCilostazol StrokePrevention Study871111117months癥狀性腦出血加無癥狀性核磁顯示血腫ASA 7 cases ( 5 symptomatic hemorrhage, 2 hemotoma in MRI)Cilostazol 1 cases p=0.0349No. 13623 Mar 200510 Oct 2004阿司匹林治療7月Microbleeding found in 39%微出血發(fā)生的危險因素二、一年后腦微出血的動態(tài)變化及影響因素93% 完成了12個月以上的隨診, 復(fù)查了MRI新增微出