The impact of blood pressure hemodynamics in acute ischemic stroke: a prospective cohort study

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Title:
The impact of blood pressure hemodynamics in acute ischemic stroke: a prospective cohort study
Series Title:
International Journal of Emergency Medicine
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Mixed Material
Language:
English
Creator:
Stead, Latha Ganti
Enduri, Sailaja
Bellolio, M. Fernanda
Jain, Anunaya R.
Vaidyanathan, Lekshmi
Gilmore, Rachel M.
Kashyap, Rahul
Weaver, Amy L.
Brown, Robert D. Jr.
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BioMed Central
Springer
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Abstract:
Objective: To assess relationships between blood pressure hemodynamic measures and outcomes after acute ischemic stroke, including stroke severity, disability and death. Methods: The study cohort consisted of 189 patients who presented to our emergency department with ischemic stroke of less than 24 hours onset who had hemodynamic parameters recorded and available for review. Blood pressure (BP) was non-invasively measured at 5 minute intervals for the length of the patient’s emergency department stay. Systolic BP (sBP) and diastolic BP (dBP) were measured for each patient and a differential (the maximum minus the minimum BP) calculated. Three outcomes were studied: stroke severity, disability at hospital discharge, and death at 90 days. Statistical tests used included Spearman correlations (for stroke severity), Wilcoxon test (for disability) and Cox models (for death). Results: Larger differentials of either dBP (p = 0.003) or sBP (p < 0.001) were significantly associated with more severe strokes. A greater dBP (p = 0.019) or sBP (p = 0.036) differential was associated with a significantly worse functional outcome at hospital discharge. Those patients with larger differentials of either dBP (p = 0.008) or sBP (0.007) were also significantly more likely to be dead at 90 days, independently of the basal BP. Conclusion: A large differential in either systolic or diastolic blood pressure within 24 hours of symptom onset in acute ischemic stroke appears to be associated with more severe strokes, worse functional outcome and early death

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University of Florida
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University of Florida
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All rights reserved by the source institution.
Resource Identifier:
doi - 10.1186/1865-1380-5-3
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AA00010462:00001


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ORIGINALRESEARCH OpenAccessTheimpactofbloodpressurehemodynamicsin acuteischemicstroke:aprospectivecohortstudyLathaGantiStead1,4*,SailajaEnduri1,MFernandaBellolio1,AnunayaRJain1,LekshmiVaidyanathan1, RachelMGilmore1,RahulKashyap1,AmyLWeaver3andRobertDBrownJr2AbstractObjective: Toassessrelationshipsbetweenbloodpressurehemodynamicmeasuresandoutcomesafteracute ischemicstroke,includingstrokeseverity,disabilityanddeath. Methods: Thestudycohortconsistedof189patientswhopresentedtoouremergencydepartmentwithischemic strokeoflessthan24hoursonsetwhohadhemodynamicparametersrecordedandavailableforreview.Blood pressure(BP)wasnon-invasivelymeasuredat5minuteintervalsforthelengthofthepatient semergency departmentstay.SystolicBP(sBP)anddiastolicBP(dBP)weremeasuredforeachpatientandadifferential(the maximumminustheminimumBP)calculated.Threeoutcomeswerestudied:strokeseverity,disabilityathospital discharge,anddeathat90days.StatisticaltestsusedincludedSpearmancorrelations(forstrokeseverity),Wilcoxon test(fordisability)andCoxmodels(fordeath). Results: LargerdifferentialsofeitherdBP(p=0.003)orsBP(p<0.001)weresignificantlyassociatedwithmore severestrokes.AgreaterdBP(p=0.019)orsBP(p=0.036)differentialwasassociatedwithasignificantlyworse functionaloutcomeathospitaldischarge.ThosepatientswithlargerdifferentialsofeitherdBP(p=0.008)orsBP (0.007)werealsosignificantlymorelikelytobedeadat90days,independentlyofthebasalBP. Conclusion: Alargedifferentialineithersystolicordiastolicbloodpressurewithin24hoursofsymptomonsetin acuteischemicstrokeappearstobeassociatedwithmoreseverestrokes,worsefunctionaloutcomeandearly deathIntroductionStrokeisassociatedwithahighmortalityandsignificant long-termfunctionaldisability.Ofthe15million patientsaffectedbystrokeworldwideyearly,theWorld HealthOrganizationreportsalmostathirdofthese patientsdie,andanotherthirdarepermanentlydisabled. Hypertensionaccountsfornearly12.7millionstrokes worldwide[1]. Closeto80%ofacuteischemicstroke(AIS)patients haveanelevatedbloodpressure[2].Theelevationof bloodpressure(BP)post-AIShasamultitudeofcauses, rangingfromchronichypertensionandsympathetic stressresponsetostroke-relatedpathologyitself[3]. Previousstudieshaveshownthatthelocationofthe stroke[4]andthetypeofstroke[5]havesomebearing onthebloodpressureresponsenotedacutelypost-AIS. Somecohortstudieshavealsosuggestedthatadmission bloodpressureprognosticatesoutcomeafteracute ischemicstroke[6],whereasothersconductedsimilarly haverefutedtheaboveresult[7,8]. Treatmentstrategiesforhypertensionpost-AISare centeredontheaimtosalvagetheischemicpenumbra [9],butthemanagementofhypertensioninpatients withacuteischemicstrokehasbeengreatlyunder debate,withnoclearconsensusonhowmuchorhow soontolowerthepressure[10]. Itiswellknownthatnormallycerebralauto-regulation maintainsperfusionoverawiderangeofsystemicblood pressures.Duringtheacutephaseofstroke,cerebral auto-regulationbecomesdysfunctional[11],andcerebral perfusionpressurebecomesdirectlydependentonsystemicpressure.Asaresultcerebralbloodflowbecomes passive,withalinearrelationshipbetweensystemicBP andcerebralbloodflowacrossawiderangeofpressure *Correspondence:lstead@ufl.edu1DepartmentofEmergencyMedicine,MayoMedicalSchool,Rochester,MN, USA FulllistofauthorinformationisavailableattheendofthearticleStead etal InternationalJournalofEmergencyMedicine 2012, 5 :3 http://www.intjem.com/content/5/1/3 2012Steadetal;licenseeSpringer.ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommonsAttribution License(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,andreproductioninanymedium, providedtheoriginalworkisproperlycited.

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values.EvenarelativelysmalldegreeofsystemicBP reductioncouldcauseasignificantriskofhypoperfusion andischemia[12].Moreover,thereisalsoimpairment ofvasomotortoneafterAIS[13].Hence,ithasbeen deliberatedwhethersystemicpressurevariationhasany consequenceonstrokeseverity,functionaldisabilityor death. Previouslypublisheddat ademonstratethatacute bloodpressurevariabilitywithinearlyhoursofpresentationtotheemergencydepartment(ED)isassociated withanincreasedriskofdeathat90days[14].Both veryhighandverylowinitialbloodpressuresare knowntobepredictorsofworseoutcomesinAIS [15,16].WithpublishedguidelinesrecommendingpermissivehypertensionintheearlycourseofAIS[17], andpromisingresultsofcurrentresearchonhemodynamicaugmentationinAIS,acautiousapproachto treatmentofhypertensioninAISisthecallofthe hour[18]. Wesoughttodetermineiftherewasanyassociation betweenfluctuationsinsystolic(sBP)ordiastolic(dBP) bloodpressurewithin24hoftheonsetofAISand strokeseverity,functionaldisabilityandmortality.MethodsThestudycohortforthisIRB(institutionalreview board)approvedprospectivecohortfollow-upstudy consistedofprospectivelyenrolledconsecutiveadult patientspresentingtoouracademicEDwithAIS. PatientswithAISonset>24hpriortopresentation/ indeterminabletimeofonsetandpatientswithnonreviewableconsecutivevitalswereexcludedfromthe finalcohort. Bloodpressure(BP)wasnon-invasivelymeasuredat5minintervalsforthelengthofthepatient sEDstaywith thePhilipsM3046APatientMonitoringSystem(Philips MedicalSystems,Andover,MA).Thesystemdesign usestheoscillometricmethod,measuringthepulsed amplitudeofpressurechangesinthecuffasitdeflates, todemarcatethesystolican ddiastolicbloodpressures. The24-hdifferentialpressure,definedasthedifference betweenthemaximumandtheminimumpressures,was calculatedforboththesBPandthedBP. Besidestheroutinedemographics,dataonstroke severityonarrival,disabilityathospitaldischargeand deathat90dayswerecollectedforthestudycohort. StrokeseverityonarrivalwasmeasuredbytheNational InstitutesofHealthStrokeScale(NIHSS),anddisability atdischargewasmeasuredbythemodifiedRankin score(mRS).Poorfunctionaloutcomewasdefinedasa mRS 3atdischarge.Deathat3monthswasascertainedbyscriptedtelephonefollow-up,statedeathcertificatesandelectronicmedicalrecordswithpriorpatient authorization. JMP8.0wasusedfortheanalysisusingSpearmancorrelations(forstrokeseverity),Wilcoxontest(fordisability)andCoxmodels(fordeath).ResultsDemographicsandcharacteristicsofthecohortare summarizedinTable1.With58.7%males,thecohort hadameanageof74years(SD=15.0).Astudyofthe TOASTclassificationofthetypeofstrokesrevealedan unusuallyhighnumberofcardio-embolicstrokesinour cohort(50.3%). Themediannumberofbloodpressurereadingswas7, withaninter-quartilerange(IQR)of4to10.Themediansystolicbloodpressureonarrival(baselinesBP)was 161mmHg(IQR144to188mmHg),andthemedian diastolicbloodpressure(baselinedBP)was80mmHg (IQR70to90mmHg).ThemediandiastolicBPdifferentialwas27mmHg(IQR16to41mmHg),andthe mediansystolicBPdifferentialwas33mmHg(IQR19 to53mmHg). Astatisticallysignificantrelationwasfoundbetween baselinehypertensionanddeathat90days,whendefiningbaselinehypertensionasbaselinesBP=170mmHg and/orbaselinedBP=110mmHg.Atotalof41.07% patientshadbaselinehypertensionusingtheabovedefinition.Therelativeriskofmortalityat90daysfor patientswithbaselinehypertensionwas2.05witha95% confidenceintervalof1.02-4.10whencomparedto patientspresentingwithlowerBP( p =0.038). Wealsodividedthecohortintothosewithorwithout oneormoreepisodesoffrankhypotensionusingthe minimummeasureddBPcutoffof70mmHg.Sixty-five percentofthecohorthaddBP<70mmHgsometime duringthestayinED.Whenthisgroupwascompared Table1StudycohortdemographicsandcharacteristicsDemographicsandcharacteristics N =189 Malegender111(58.7%) Age(years) Mean(SD) 74.0(15.0) Range 26-98 TOAST 1.Largevessel 20(10.6%) 2.Cardioembolic 95(50.3%) 3.Smallvessel 29(15.3%) 4.Other,nocausesormultiplecauses45(23.8%) NIHSS Mean(SD) 9.9(8.5) Median(IQR) 6.0(3.8-15) Range 0-37 Rankinscoreatdismissal 0-2 58(31.0%) 3-6 129(69.0%) Stead etal InternationalJournalofEmergencyMedicine 2012, 5 :3 http://www.intjem.com/content/5/1/3 Page2of4

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tothosewithdBP>70mmHg,therewashoweverno statisticaldifferenceinstrokeseverity,outcomesof deathat90daysormRSatdischarge. ThemedianNIHSSscoreatarrivalwas6.0,withan interquartilerangeof3.75to15.0.Patientswithmore severestrokeshadlargerdifferentialdBP( p =0.003) anddifferentialsBP( p <0.001)(Spearmancorrelation r =0.22and r =0.26,respectively).TherewasnoassociationfoundbetweenbaselinehypertensionandNIHSS scoreonarrival( p =0.4734). Atotalof129patients(68.3%)hadaRankinscoreof 3ormoreathospitaldischarge(badoutcome).The mediandifferentialdBPforaRankinscore0-2was22.5 mmHg,whileforaRankinscoreof3ormorewas29 mmHg.ThemediandifferentialsBPforaRankinscore 0-2was26mmHg,whileforaRankinscoreof3or morewas36mmHg.AgreaterdBP( p =0.019)orsBP ( p =0.036)differentialwasassociatedwithasignificantlyworsefunctionaloutcomeathospitaldischarge (Table2).Again,aswithNIHSS,therewasnorelation betweenbaselinehypertensionandbadoutcome(p = 0.486). Atotalof40deaths(21.2%)occurredwithinthefirst 90days.ThosewithlargerdifferentialsofeitherdBP( p =0.008)orsBP(0.007)weresignificantlymorelikelyto bedeadat90days(Table3).Thisassociationretained statisticalsignificanceeven afteradjustingforstroke severity.DiscussionMosthemodynamicvariables,includingsystolicblood pressure,diastolicbloodpressure,meanarterialpressure pulsepressureandheartrate,havebeenassociatedwith poorfunctionaloutcomefollowingstroke[19].Likeearlierstudies,wetoofoundthatbaselinehypertensionwas associatedwithahigherriskofdeathat90dayspoststroke,althoughitwasnotassociatedwithstrokeseverityatpresentation.Forourcohortthishypertensioncutoffwasabloodpressureof170/110mmHg. Withtheongoingdiscussiononmanagementofblood pressureinacutestageofisc hemicstroke,researchers havetriedtoestablishrelat ionshipsbetweenoutcomes andbloodpressure.OnesuchstudybyToyodaetal.in 2009reportedthatsystolicbloodpressurevaluesbetween 12and36hpost-admissionwerepredictiveofneurologicaldeterioration,buttheauthorsdidnotfindthesame forbloodpressurevalueswithintheinitial6h[20]. Recentlyconcernhasbeenexpressedovertherelation betweenhigherpre-treatme ntsystolicbloodpressure andpoorre-canalizationinpatientstreatedwithIVtPA [21].Ourownresearchin2006revealedthatwidefluctuationsinbloodpressureinthefirst3hofemergency departmentstaypredictedmortalityover3months post-stroke[14]. Thisstudybuildsonourpriorworkonbloodpressure andacuteischemicstroke(14,15),afollow-uptoour earlierstudy.Wequestionedwhetheritwasindeedthe BPdifferentialthatresultedinpooroutcomesorrather anepisodeofhypotensionduringtheearlyEDcourse thatwastheculprit.Whenwecomparedthehypotensiveandnon-hypotensivegroups,wefoundthatthere wasnodifferenceintheoutcomesofdeathorfunctional Rankinscores,suggestingthatBPfluctuationwasan independentpredictorofpooroutcome.TheVISTA collaborationpresentedsimilarfindings,highlighting thatfluctuationsinsystolicbloodpressurewereassociatedwithworseoutcomepost-stroke[22]. Ourstudyalsofoundthatpatientswithmoresevere strokeshadgreaterfluctuationsinbloodpressure,but nottheinitialbaselinebloodpressure.Thisledtothe argumentthatitwastheinit ialseverityofthestroke thattranslatedtotheworseoutcome.However,when weadjustedfortheNIHSSseverityofstrokes,wefound thatthesBPdifferentialanddBPdifferentialco-related independentlywithdeathat90days. Hypotensionrelativetothebaseline,causingregional hypo-perfusion,isanincreasinglyunderstoodconcept immediatelyfollowinganischemicstroke.Theresultsof thepresentstudyandensuingdiscussionmaytempt onetosurmisethatbloodpressurevariabilityisbadand thatthereforesomehowtigh tlycontrollingitwithina specifiedrangeisthenextlogicalstep.Cautionmustbe exercisedhere.Onecannotassumethat correcting the associationwillresultinimprovedoutcome.Itisindeed Table2ComparisonbetweenRankinscoreandBPBP(mmHg) Rankinscore 0-2 ( n =41) Rankinscore 3-6 ( n =88) pvalue BaselinesBP(meanSD)170.835.3166.532.20.490 BaselinedBP(meanSD)80.921.080.222.00.855 ChangesBP(median, 25%-75%IQR) 26.0,15.5-48.536.0,22.0-53.5 0.036 ChangedBP(median,25%75%IQR) 22.5,12.0-37.029.0,18.5-45.0 0.019p-valueslessthan0.05consideredstatisticallysignificantareshowninbold. Table3ComparisonbetweenmortalityandBPBP(mmHg) Aliveat90 days ( n =149) Deadat90 days ( n =40) pvalue BaselinesBP(meanSD)168.832.4163.834.70.449 BaselinedBP(meanSD)80.720.380.425.20.956 ChangesBP(median, 25%-75%IQR) 30.0,17.0v51.542.5,29.0-61.0 0.033 ChangedBP(median,25%75%IQR) 25.0,14.0v38.035.0,23.3-51.8 0.006p-valueslessthan0.05consideredstatisticallysignificantareshowninbold.Stead etal InternationalJournalofEmergencyMedicine 2012, 5 :3 http://www.intjem.com/content/5/1/3 Page3of4

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thenextstepinclinicalinvestigation,butnotquite readyforimplementationintoclinicalpracticebefore thehypothesisisdefinitivelyinvestigatedinacontrolled trial.ConclusionFluctuationsinbloodpressureinthesettingofacute ischemicstrokeappeartoimpartanegativeimpacton strokeseverity,functionaloutcomeanddeathat90 days.Thisisahypothesis-generatingstudythatasks whetherpharmacologiccontr olofthesebloodpressure fluctuationswouldresultinimprovedclinicaloutcomes.PatientconsentThisprotocolwasapprovedbythedepartmentofEmergencyMedicineResearchCommittee(minuteexcerpt attached).ItwasalsoapprovedbytheMayoClinicInstitutionalReviewBoardasprotocol1054-04.CompetinginterestsstatementsTheauthorsdeclarethattheyhavenocompeting interests.Authordetails1DepartmentofEmergencyMedicine,MayoMedicalSchool,Rochester,MN, USA2DepartmentofNeurology,MayoMedicalSchool,Rochester,MN,USA3DivisionofBiostatistics,MayoMedicalSchool,Rochester,MN,USA4DepartmentofEmergencyMedicine,UniversityofFlorida,1329SW16thStreet,Gainesville,FL,32610,USA Authors contributions LGSconceivedthestudy,collectedthedataandwrotethepaper.SE,MFB, AJ,LV,RG,andRKcollecteddataandreviewedthepaper.ALWanalyzedthe data.RDBsupervisedtheproject.Allauthorsreadandapprovedthefinal manuscript. 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BloodPressMonit 2009, 14(1) :20-25.doi:10.1186/1865-1380-5-3 Citethisarticleas: Stead etal .: Theimpactofbloodpressure hemodynamicsinacuteischemicstroke:aprospectivecohortstudy. InternationalJournalofEmergencyMedicine 2012 5 :3.Stead etal InternationalJournalofEmergencyMedicine 2012, 5 :3 http://www.intjem.com/content/5/1/3 Page4of4


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