血壓控制與腦出血治療和預防-醫(yī)學教學課件

血壓控制與腦出血治療和預防北京大學第一醫(yī)院神經科黃一寧教授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北大醫(yī)院臨床診治方案平掃CT應該作為首選，對腦出血和蛛網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、蛛網膜下腔出血、腦室出血、堵塞后出血以及腦實質出血。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。下述步驟應該是同步進行

評估生命體癥：判斷患者做影像學檢查時是否能忍受，是否要插管。假設認為需要插管，可以使用超短作用的神經肌肉阻斷劑或者鎮(zhèn)靜劑，防止長時間影響觀察患者運動功能和神經功能。對于血壓嚴重升高的患者應該評估是否有心肌的損傷。血液檢查：PT、INR、PTT、血小板計數和全血計數、D－Dimer、纖維蛋白原、電解質、BUN、Cr、血糖、肝功能、血型。需要與神經外科聯系：小腦出血時神經外科急癥；非優(yōu)勢半球的腦葉出血，臨床神經功能進行性加重；對于特殊患者，如年輕患者、優(yōu)勢半球不清楚，等情況下，考慮需要減壓術者。根據指南控制血壓。所有需要連續(xù)靜脈降壓的患者，都應該急診放置動脈導管，監(jiān)測血壓和中心靜脈壓，同時使用靜脈降壓藥。一旦決定藥靜脈降壓治療，必須指定專人床旁監(jiān)測血壓和治療效果，直至血壓得到控制。Roleofbloodpressureobservationalstudies-mortalityadmissionBPandmortalitySBP(mmHg)1monthmortality(%)FogelholmVemmosOnsetofICH3-66-12hours12hrstooneweek1-4weeksmonthsBPloweringhaemorrhagerebleedingoedemastrokerecurrenceBPlowering

Potentialtherapeuticmechanisms腦出血患者血壓控制方案

拉貝洛爾labetalol5－100mg/h，間斷注入，每次10－40mg，或者 連續(xù)點滴2－8mg/min

我國藥典禁忌在腦出血使用拉貝咯爾

艾司洛爾esmolol

負荷量500mcg/kg；維持量50－200mcg.kg-1min

硝普鈉nitroprusside 0.5-10mcg.kg-1min-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0.625-1.2mgq6h,根據需要調節(jié)劑量

GuidelinesforAcuteBPManagement對于腦出血早期幾個小時內可以根據下述步驟：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180－230mmHg，舒張壓105－140mmHg，或者平均動脈壓≥130mmHg，間隔20分鐘測量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<105mmHg，暫緩使用抗高血壓藥，除非疑心出現了冠狀動脈缺血性疾病。選擇用藥應該根據患者實際情況和禁忌癥，如拉貝洛爾不藥用于哮喘的患者。如果有顱內壓監(jiān)測，應該保持腦灌注壓>70mmHg。當疑心由于降低血壓引起臨床病癥惡化，應考慮調整血壓。問題什么時候降血壓降到多少適宜降壓速度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阿司匹林已經成為公認的缺血性卒中二級預防首選藥物GuidelinesforpreventionofstrokeinpatientswithischemicstrokeorTIAs,Stroke,2006;37:577-617AHA/ACCguidelinesforsecondaryprevetionforpatientswithcoronaryandotheratheroscleroticvasculardisease:2006update,,JACC2006；47(10〕，2130NATUREREVIEWS-DRUGDISCOVERYVOLUME2;OCTOBER2003;1-15StrongerInhibitionofPlatelets:CombinedifferentPathways+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

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%)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0369121518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%Lancet2004;364:331-37N=75991-1.5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，對高危的缺血性腦血管病患者，在氯吡格雷標準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/風險比)增加ASA導致更多的威脅生命的出血事件，主要是胃腸道出血和顱內出血。?DefinedasrecentISorTIAwithpreviousischemiceventordiabetesClopidogrelforHighAtherothromboticRiskandIschemicStabilization,ManagementandAvoidance

(CHARISMA)

氯吡格雷用于動脈粥樣硬化血栓形成高危及穩(wěn)定、處理和防止缺血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，雙盲，隨機，雙模擬，阿司匹林對照設計:spsCCilostazolStrokePreventionStudyCSPSTrial入組標準年齡：18-75卒中發(fā)病1-6個月影像學(CT/MRI)確認腦梗死ModifiedRankinScale<4

沒有嚴重的系統(tǒng)疾病填寫知情同意書spsCCilostazolStrokePreventionStudy研究設計spsCCilostazolStrokePreventionStudy主要終結指標次要終結指標平安性:卒中復發(fā)〔梗死，出血，蛛網膜下腔出血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異常設計流程spsCCilostazolStrokePreventionStudyR=Randomization12~18monthsdouble-blind,double-dummy,treatmentcilostazol100mgbid(n=360)ASA100mgqd6thmonth12thmonth18thmonthFollow-upfinish3thmonth1stmonth1~6monthaftercerebralinfarctionRTreatmentstart(n=360)0dayScreeningbyPE/MRI/LAB.etcMRI主要終結指標累計Kaplan-MeierCurve終結分析主要終點指標Aspirin5.27%Cilostazol3.26%RR38.1%腦出血/腦梗死Aspirin33.3%Cilostazol9.1%腦出血患者123456

PeriodofNo.CodeSexAgeDrugTreatmentOutcome136540559437692538MMMMMM695755534266aspirinaspirincilostazolaspirinaspirinaspirinPVSRecoveringRecoveringRecoveringRecoveringDeathspsCCilostazolStrokePreventionStudy871111117months病癥性腦出血加無病癥性核磁顯示血腫ASA7cases(5symptomatichemorrhage,2 hemotomainMRI)Cilostazol1casesp=0.0349No.13623Mar200510Oct2004阿司匹林治療7月Microbleedingfoundin39%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%)