血压控制与脑出血治疗和预防-医学教学课件

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ynhuang@sinaPrimaryIntracerebralHaemorrhage10-15%allstrokes(Caucasians)20-30%inAsian/AfricanPathology(80-90%ofallICH)HypertensiveangiopathyAmyloidangiopathySitesBasalGangliaPutamen(40%),thalamus(15%),caudate(5-10%)Cerebellum(10%),pons(10%)Lobar(10-20%)HaematomaevolutionEarlyhaematomaexpansionPeri-haematomaloedemainICHPreciseaetiologyunclearcytotoxicvsvasogenicIsthereaperi-haematomal‘ischaemicpenumbra?’RationalacuteBPloweringrequiresbetterunderstandingofperi-haematomaloedemaSurgicaltreatment

STICHtrialresultsMedicaltreatment

rFVII(NovoSeven®)Mayeretal.NEJM2005;352:777-85ReductionofhaematomaexpansionMayeretal.NEJM2005;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、D－Dimer、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。Roleofbloodpressureobservationalstudies-mortalityadmissionBPandmortalitySBP(mmHg)1monthmortality(%)FogelholmVemmosOnsetofICH3-66-12hours12hrstooneweek1-4weeksmonthsBPloweringhaemorrhagerebleedingoedemastrokerecurrenceBPlowering

Potentialtherapeuticmechanisms脑出血患者血压控制方案

拉贝洛尔labetalol5－100mg/h，间断注入，每次10－40mg，或者 连续点滴2－8mg/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50－200mcg.kg-1min

硝普钠nitroprusside 0.5-10mcg.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0.625-1.2mgq6h,根据需要调节剂量

GuidelinesforAcuteBPManagement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180－230mmHg，舒张压105－140mmHg，或者平均动脉压≥130mmHg，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<105mmHg，暂缓使用抗高血压药，除非疑心出现了冠状动脉缺血性疾病。选择用药应该根据患者实际情况和禁忌症，如拉贝洛尔不药用于哮喘的患者。如果有颅内压监测，应该保持脑灌注压>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。问题什么时候降血压降到多少适宜降压速度INTERACTpilotphase

(LancetNeurology2021;7:391-399.)PathophysiologyElevatedBloodPressureOngoingbleedingRe-bleedingHaematomasizePooroutcomeCerebraloedemaVanguardPhase

ProtocolSchemaRandomisationAcuteICH-onsetwithin6hoursSBP≥150and≤220mmHgRepeatCTscans24+72hrsVitalsignsandBPover7days28dayand3monthfollow-upIntensive

BPloweringTargetSBP<140mmHgGuideline-basedBPmanagementTargetSBP<180mmHgSystolicbloodpressuredifferencesCrudemean(SD)changeinhematomavolumebygroupVolume(ml)GuidelinegroupIntensivegroupBaseline24hours12.715.414.215.2

Clinicaloutcomesat90daysEarlyintensivebloodpressureloweringenhanceshematomaresolutionbutdoesnotaffectperihematomaedema:YiningHuangPekingUniversityFirstHospital,Beijing,ChinaOnbehalfofCAnderson,QLi,EHeeley,BPeng,CSkulina,JWang,fortheINTERACTInvestigatorsSecondaryaims Todeterminetheeffectsofearlyintensivebloodpressureloweringtreatmentonhematomaandperihematomaedemagrowthover72hoursSecondaryanalyses:patientflow404Patientsrandomized201Guideline-basedBPlowering145inhematomaanalysis1PatientnotICH151inhematomaanalysis131inedemaanalysis139inedemaanalysis14Unabletoestimateedemavolume12Unabletoestimateedemavolume56MissingCTdataat24hand/or72h51MissingCTdataat24hand/or72h203EarlyintensiveBPloweringMeanBPafterrandomization2000153045606121824150100502345672890MinutesHoursDaysMeanbloodpressure(mmHg)GuidelineIntensiveΔSBP14mmHgat1hour(P<0.0001)ΔSBP12mmHgfrom1-24hours(P<0.0001)ΔSBP11mmHgfrom1-3days(P<0.0001)GuidelineBaselineto24hIntensiveGuidelineBaselineto72hIntensive151050Absoluteincreaseinedemavolume(ml)OverallΔ-2.4mlover72hours(P=0.1)usingrepeatedmeasure(Adjustmentsweremadeforlocationandbaselinevolumeofhematoma,andtimefromonsettoCT)Δ-2.1ml(P=0.09)Δ-2.7ml(P=0.1)Adjustedmean(95%CI)valuesforabsolute

increaseinedemavolume(mL)GuidelineBaselineto24hIntensiveGuidelineBaselineto72hIntensive120100806020Relativeincreaseinedemavolume(%)40OverallΔ+2%over72hours(P=0.1)usingrepeatedmeasure(Adjustmentsweremadeforlocationandbaselinevolumeofhematoma,andtimefromonsettoCT)Δ-3%(P=0.8)Δ+6%(P=0.6)Adjustedmean(95%CI)valuesforrelative

increaseinedemavolume(%)SummaryofresultsHematomaanalysisEarlyintensiveBPloweringtreatmentloweredsystolicBPby>10mmHgwasassociatedwithreductioninabsolute(-2.8ml;P=0.002)andrelative(-10%;P=0.04)increaseinhematomavolumeover72hoursPerihematomaedemaanalysisEarlyintensiveBPloweringhadnocleareffectsonabsoluteorrelativeincreaseinperihematomaedemavolumeover72hoursCilostazolv.s.AspirininSecondaryStrokePrevention

YNHuang,CYan,WJiang,etalLancetNeurology2021,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GuidelinesforpreventionofstrokeinpatientswithischemicstrokeorTIAs,Stroke,2006;37:577-617AHA/ACCguidelinesforsecondaryprevetionforpatientswithcoronaryandotheratheroscleroticvasculardisease:2006update,,JACC2006；47(10〕，2130NATUREREVIEWS-DRUGDISCOVERYVOLUME2;OCTOBER2003;1-15StrongerInhibitionofPlatelets:CombinedifferentPathways+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)Aspirin+ClopidogrelAspririn+placebo

036912P<0.0010.140.120.100.080.060.040.020.00MonthsofFollow-upCumulativeHazardRateVascularDeath+MI+Strokeafter4weeksandafter4.5MonthAddedBenefitofClopidogreltoASAtreatmentinUnstaibleAnginaPatientsRRR:6.4%(95%CI:-4.6%到16.3%)(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0369121518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%Lancet2004;364:331-37N=75991-1.5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。†DefinedasrecentISorTIAwithpreviousischemiceventordiabetesClopidogrelforHighAtherothromboticRiskandIschemicStabilization,ManagementandAvoidance

(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NEnglJMed2006,354:106121824301086420月Accumulationofevents（％）aspirinclopidogrelplusaspirinP=0.22CHARISMANEnglJMed2006,354:1Endpoints:MI,Stroke,VasculardeathCHARISMASignificantlyincreasedofbleedingeventsinthecombinationtreatmentofclopidogrelplusaspirinPrimarySafetyRR〔95％CI〕pvalueSeverebleeding

1.25(0.97-1.61)0.09Moderatebleeding

1.62(1.27-2.10)<0.00125%62%ProfessNATUREREVIEWS-DRUGDISCOVERYVOLUME2;OCTOBER2003;1-15InhibitionofPlatelets:BydifferentPathways多中心，双盲，随机，双模拟，阿司匹林对照设计:spsCCilostazolStrokePreventionStudyCSPSTrial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ModifiedRankinScale<4

没有严重的系统疾病填写知情同意书spsCCilostazolStrokePreventionStudy研究设计spsCCilostazolStrokePreventionStudy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spsCCilostazolStrokePreventionStudyR=Randomization12~18monthsdouble-blind,double-dummy,treatmentcilostazol100mgbid(n=360)ASA100mgqd6thmonth12thmonth18thmonthFollow-upfinish3thmonth1stmonth1~6monthaftercerebralinfarctionRTreatmentstart(n=360)0dayScreeningbyPE/MRI/LAB.etcMRI主要终结指标累计Kaplan-MeierCurve终结分析主要终点指标Aspirin5.27%Cilostazol3.26%RR38.1%脑出血/脑梗死Aspirin33.3%Cilostazol9.1%脑出血患者123456

PeriodofNo.CodeSexAgeDrugTreatmentOutcome136540559437692538MMMMMM695755534266aspirinaspirincilostazolaspirinaspirinaspirinPVSRecoveringRecoveringRecoveringRecoveringDeathspsCCilostazolStrokePreventionStudy871111117months病症性脑出血加无病症性核磁显示血肿ASA7cases(5symptomatichemorrhage,2 hemotomainMRI)Cilostazol1casesp=0.0349No.13623Mar200510Oct2004阿司匹林治疗7月Microbleedingfoundin39%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93%完成了12个月以上的随诊,复查了MRI新增微出血50例NewlesionsfoundinSecondMRI━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ITTPP工程────────────────────────────ASACilostrazolASACilostrazol───────────────────────────────────────────NewInfarct(Flair)no305(98.39%)284(97.26%)305(98.39%)283(97.25%)yes5(1.61%)8(2.74%)