【醫(yī)學(xué)課件大全】血壓控制與腦出血治療和預(yù)防 (64p)

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ynhuangsina Primary 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 (1

2、0-20%)Haematoma 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 ICHPrecise aetiology unclearcytotoxic vs vasogenicIs there a peri-haematomal ischaemic penumbra?Rational acute

3、BP lowering 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北大醫(yī)院臨床診治方案平掃CT應(yīng)該作為首選，對(duì)腦出血和蛛網(wǎng)膜下腔出血均很敏感。核磁對(duì)可疑的腦出血診斷和處理上也很有幫助。腦

4、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、堵塞后出血以及腦實(shí)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(dòng)脈瘤破裂。下述步驟應(yīng)該是同步進(jìn)行評(píng)估生命體癥：判斷患者做影像學(xué)檢查時(shí)是否能忍受，是否要插管。假設(shè)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，防止長(zhǎng)時(shí)間影響觀察患者運(yùn)動(dòng)功能和神經(jīng)功能。對(duì)于血壓嚴(yán)重升高的患者應(yīng)該評(píng)估是否有心肌的損傷。血液檢查：PT、INR、PTT、血小板計(jì)數(shù)和全血計(jì)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(shí)神經(jīng)外科急癥；非優(yōu)勢(shì)半球的腦葉出血，臨床神經(jīng)功能進(jìn)行性加重；對(duì)于

5、特殊患者，如年輕患者、優(yōu)勢(shì)半球不清楚，等情況下，考慮需要減壓術(shù)者。根據(jù)指南控制血壓。所有需要連續(xù)靜脈降壓的患者，都應(yīng)該急診放置動(dòng)脈導(dǎo)管，監(jiān)測(cè)血壓和中心靜脈壓，同時(shí)使用靜脈降壓藥。一旦決定藥靜脈降壓治療，必須指定專人床旁監(jiān)測(cè)血壓和治療效果，直至血壓得到控制。Role of blood pressureobservational studies - mortalityadmission BP and mortalitySBP (mm Hg)1 month mortality (%)FogelholmVemmosOnset of ICH3-6 6-12 hours12hrs to one week1

6、-4 weeksmonthsBP loweringhaemorrhagerebleedingoedemastroke recurrenceBP loweringPotential therapeutic mechanisms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(diǎn)滴 28mg/min 我國(guó)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-1min-1 尼卡地平 nicardipine 5m

7、g/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 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

8、) 160-180/90-105 mm Hg (non-HT)UK (2004)if complications are apparentNot described對(duì)于腦出血早期幾個(gè)小時(shí)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(cè)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(dòng)脈壓 130 mmHg， 間隔20分鐘測(cè)量2次，開始靜脈使用拉貝洛爾、艾司洛爾、依那普利，防止口服或舌下含服硝苯地平。收縮壓180mmHg 舒張壓70mmHg。當(dāng)疑心由于降低血壓引起臨床病癥惡化，應(yīng)考慮調(diào)整血壓。問題什么時(shí)候降血

9、壓降到多少適宜降壓速度INTERACT pilot phase(Lancet Neurology 2021; 7: 391-399.)PathophysiologyElevated Blood PressureOngoing bleedingRe-bleedingHaematoma sizePoor outcomeCerebral oedema Vanguard PhaseProtocol SchemaRandomisationAcute ICH - onset within 6 hoursSBP 150 and 220 mmHgRepeat CT scans 24 + 72 hrsVital

10、 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 hours12.715.414.215.2 C

11、linical 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, %78750.97Early intensive blood pressure lower

12、ing 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 aimsTo determine the effects of early intensive blood press

13、ure 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 analysis139 in edema analysis14 Unable to estimate edema v

14、olume12 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 randomization2000153045606121824150100502345672890MinutesHoursDaysMean blood pressure (mm Hg)GuidelineIntensiveSBP 14 mm Hg at 1 hour (P0.0001)S

15、BP 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 edema analysisEarly intensive BP lowering had no clear effects on absolute or relat

16、ive increase in perihematoma edema volume over 72 hoursCilostazol v.s. Aspirin in Secondary Stroke PreventionYN Huang, C Yan, W Jiang, et al Lancet Neurology 2021, May阿司匹林已經(jīng)成為公認(rèn)的缺血性卒中二級(jí)預(yù)防首選藥物Guidelines for prevention of stroke in patients with ischemic stroke or TIAs, Stroke, 2006;37:577-617AHA/ACC

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

18、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 RRR: 6.4% (95% CI: - 4.6% 到 16.3%)(

19、p=0.244) ASA + 氯吡格雷 (15.7%) 撫慰劑 + 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危患者中對(duì)動(dòng)脈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，并為給高危的腦血管病患者病人帶來額外的臨床益處MATCH研究顯示，對(duì)高危的缺血性腦血管病患者，在氯吡格雷標(biāo)準(zhǔn)治療的根底上增加阿司匹林，阿司匹林沒有帶來更多的臨床益處(療效/風(fēng)險(xiǎn)

20、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(dòng)脈粥樣硬化血栓形成高危及穩(wěn)定、處理和防止缺血N Engl J Med 2006,354:10 6 12 18 24 301086420月Accumulation of

21、 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 aspirinPrimary Safety RR95CI p valueSevere bleeding 1.25(0.97-1.61) 0.09Moderate bleed

22、ing 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(jī)，雙模擬，阿司匹林對(duì)照設(shè)計(jì):spsCCilostazol StrokePrevention StudyCSPS Trial入組標(biāo)準(zhǔn)年齡：18-75卒中發(fā)病1-6個(gè)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spsCC

23、ilostazol StrokePrevention Study研究設(shè)計(jì)spsCCilostazol StrokePrevention Study主要終結(jié)指標(biāo)次要終結(jié)指標(biāo) 平安性: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(shí)驗(yàn)室化驗(yàn)異常; ECG 異常設(shè)計(jì)流程spsCCilostazol StrokePreventionStudyR = Randomization1218months double-blind,double-dummy,treatmentcilostazol 100mg bid

24、(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(jì) Kaplan-Meier Curve終結(jié)分析主要終點(diǎn)指標(biāo)Aspirin 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 Peri

25、od of No. Code Sex Age Drug Treatment Outcome 136540559437692538MMMMMM695755534266aspirinaspirincilostazolaspirinaspirinaspirinPVSRecoveringRecoveringRecoveringRecoveringDeathspsCCilostazol StrokePrevention Study871111117months病癥性腦出血加無病癥性核磁顯示血腫ASA 7 cases ( 5 symptomatic hemorrhage, 2 hemotoma in MRI)Cilostazol 1 cases p=0.0349No. 13623