【医学课件大全】血压控制与脑出血治疗和预防 (64p)

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北大医院临床诊治方案平扫CT应该作为首选，对脑出血和蛛网膜下腔出血均很敏感。核磁对可疑的脑出血诊断和处理上也很有帮助。脑

4、出血包括硬膜外和硬膜下出血、蛛网膜下腔出血、脑室出血、堵塞后出血以及脑实质出血。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。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是否能忍受，是否要插管。假设认为需要插管，可以使用超短作用的神经肌肉阻断剂或者镇静剂，防止长时间影响观察患者运动功能和神经功能。对于血压严重升高的患者应该评估是否有心肌的损伤。血液检查：PT、INR、PTT、血小板计数和全血计数、DDimer、纤维蛋白原、电解质、BUN、Cr、血糖、肝功能、血型。需要与神经外科联系：小脑出血时神经外科急症；非优势半球的脑叶出血，临床神经功能进行性加重；对于

5、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。根据指南控制血压。所有需要连续静脉降压的患者，都应该急诊放置动脉导管，监测血压和中心静脉压，同时使用静脉降压药。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。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 5m

7、g/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 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对于脑出血早期几个小时内可以根据下述步骤：收缩压 230mmHg， 或者舒张压 140mmHg，间隔5分钟测量2次血压，开始使用硝普钠收缩压 180230 mmHg， 舒张压 105140mmHg，或者平均动脉压 130 mmHg， 间隔20分钟测量2次，开始静脉使用拉贝洛尔、艾司洛尔、依那普利，防止口服或舌下含服硝苯地平。收缩压180mmHg 舒张压70mmHg。当疑心由于降低血压引起临床病症恶化，应考虑调整血压。问题什么时候降血

9、压降到多少适宜降压速度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

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+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 (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%) 抚慰剂 + 氯吡格雷 (16.7%)IS、MI、VD、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的高危患者中对动脉粥样硬化血栓形成的处理MATCH： ARR: 1.0% Lancet 2004; 364: 331-37N=7599 1-1.5年增加ASA，并为给高危的脑血管病患者病人带来额外的临床益处MATCH研究显示，对高危的缺血性脑血管病患者，在氯吡格雷标准治疗的根底上增加阿司匹林，阿司匹林没有带来更多的临床益处(疗效/风险

20、比)增加ASA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。 Defined as recent IS or TIA with previous ischemic event or diabetesClopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance(CHARISMA)氯吡格雷用于动脉粥样硬化血栓形成高危及稳定、处理和防止缺血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，双盲，随机，双模拟，阿司匹林对照设计:spsCCilostazol StrokePrevention StudyCSPS Trial入组标准年龄：18-75卒中发病1-6个月 影像学 (CT/MRI)确认脑梗死 Modified Rankin Scale 4 没有严重的系统疾病 填写知情同意书spsCC

23、ilostazol StrokePrevention Study研究设计spsCCilostazol StrokePrevention Study主要终结指标次要终结指标 平安性:卒中复发梗死，出血，蛛网膜下腔出血MRI 显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; 实验室化验异常; ECG 异常设计流程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主要终结指标累计 Kaplan-Meier Curve终结分析主要终点指标Aspirin 5.27%Cilostazol 3.26%RR 38.1% 脑出血/脑梗死Aspirin 33.3%Cilostazol 9.1% 脑出血患者123456 Peri

25、od of No. Code Sex Age Drug Treatment Outcome 136540559437692538MMMMMM695755534266aspirinaspirincilostazolaspirinaspirinaspirinPVSRecoveringRecoveringRecoveringRecoveringDeathspsCCilostazol StrokePrevention Study871111117months病症性脑出血加无病症性核磁显示血肿ASA 7 cases ( 5 symptomatic hemorrhage, 2 hemotoma in MRI)Cilostazol 1 cases p=0.0349No. 13623