Management of AcuteManagement of AcuteIschemic StrokeIschemic Stroke

Ethan Cumbler M.D.Ethan Cumbler M.D.Assistant Professor Internal MedicineAssistant Professor Internal Medicine

University of Colorado HospitalUniversity of Colorado HospitalUCH Stroke CouncilUCH Stroke Council

20102010

Disclosures/RelationshipsDisclosures/Relationships Dr. Cumbler serves on the AHA/ASA Pacific/Mountain Stroke Quality Speakers Bureau Dr. Cumbler serves on the AHA/ASA Pacific/Mountain Stroke Quality Speakers Bureau

Dr. Cumbler is the National Stroke Association Dr. Cumbler is the National Stroke Association’’s Course Director fors Course Director forOptimizing Care for In-hospital StrokeOptimizing Care for In-hospital Stroke

No commercial conflict of interests in the last 3 yearsNo commercial conflict of interests in the last 3 years

OBJECTIVESOBJECTIVES

1. Use validated risk stratification tools to determine which TIA patients need admission

3. Identify appropriate means to manage co-morbid illness after stroke

4. Describe mechanisms to reduce the risk of complications following stroke

5. Institute evidence based secondary prevention therapies.

Ischemic StrokeIschemic Stroke700,000 ischemic strokes yearly700,000 ischemic strokes yearly–– Approximately one stroke every 45 secondsApproximately one stroke every 45 seconds

200,000 are recurrent events200,000 are recurrent events

Leading cause of disability in the USLeading cause of disability in the US

Quality stroke care attractive to hospitalsQuality stroke care attractive to hospitals–– Ischemic stroke treated with Ischemic stroke treated with tPA tPA pays extra $6000pays extra $6000

Heart Disease and Stroke Statistics- 2007 Update . Circulation 2007;6:115(5):e69-e171How Diagnosis-Related Group 559 Will Change the US Medicare Cost Reimbursement Ratio for Stroke Centers. Stroke 2007;38:1309-1312Colorado Stroke Alliance Data 2008. Presented by Dr. Don Smith at Rocky Mountain Stroke Summit Dec 2008

Non-contrast Head CT negativeNon-contrast Head CT negative

The patients symptoms begin improving inThe patients symptoms begin improving inthe Emergency Departmentthe Emergency Department

tPA tPA not given due to mild and resolvingnot given due to mild and resolvingsymptomssymptoms

Complete resolution 90 minutes after onsetComplete resolution 90 minutes after onset

Should she be admitted?Should she be admitted?

TIAsTIAs

Within 3 months 10% will have had a strokeWithin 3 months 10% will have had a stroke

Half will occur in the first 48 hoursHalf will occur in the first 48 hours

2/3 of second strokes cause disability2/3 of second strokes cause disability

21% are fatal21% are fatal

Rationale for HospitalizationRationale for Hospitalization1.1. Allows rapid initiation of Allows rapid initiation of tPA tPA for 2for 2ndnd CVA CVA

2.2. Facilitates evaluation and 2Facilitates evaluation and 200 prevention prevention

National Stroke Association GuidelinesNational Stroke Association Guidelines–– Evaluation should occur in 24-48 hoursEvaluation should occur in 24-48 hours

MRIMRICarotid U/SCarotid U/SEchoEchoTelemetryTelemetryLipidsLipids

Antiplatelet ORAnticoagulant

StatinCarotid Endarterectomy

Better outcomes in 1st 2 wks

National Stroke Association Guidelines for the Management of Transient Ischemic Attacks. Ann Neurol 2006;60:301-313

Theoretically This Could OccurTheoretically This Could OccurOutpatientOutpatient…………

Three fourths of Three fourths of TIAs TIAs in the ED are sent homein the ED are sent home–– Subsequent delays in evaluationSubsequent delays in evaluation–– 1/3 not discharged on 1/3 not discharged on antithromboticantithrombotic

Only 2% of Only 2% of TIAs TIAs seen in clinic are admittedseen in clinic are admitted–– Less than half with Less than half with afib afib started on started on warfarinwarfarin–– 1/3 did not have workup for > 30 days1/3 did not have workup for > 30 days

Hospitalization associated with decreased risk ofHospitalization associated with decreased risk ofsecond stroke (HR 0.73)second stroke (HR 0.73)–– But increases resource utilizationBut increases resource utilization

Management and Outcomes of Transient Ischemic Attacks in Ontario. CMAJ 2004; 170:1099-104New Transient Ischemic Attack and Stroke: Outpatient Management by Primary Care Physicians. Arch Intern Med 2000;160:2941-2946The High Risk of Stroke Immediately After Transient Ischemic Attack: A Population Based Study. Neurol 2004;62:2015-2020

Predicting Early Second StrokePredicting Early Second Stroke

ABCDABCD22 Score Score

1110-59 min10-59 min

11PresentPresentDiabetesDiabetes

22> 60 min > 60 min ORORDurationDuration

11SpeechSpeechImpairmentImpairment

22UnilateralUnilateralWeakness Weakness OROR

Clinical DeficitClinical Deficit

11SBP SBP >> 140 140 ororDBP DBP >> 90 90

Blood PressureBlood Pressure

11>> 60 years 60 yearsAgeAge

PointsPointsClinical FeatureClinical Feature

Validation and Refinement of Scores to Predict Very Early Stroke Risk after Transient Ischaemic Attack. Lancet 2007;369:283-92

Predicting Early Second StrokePredicting Early Second StrokeABCDABCD22 Score Score

8.1%8.1%4.1%4.1%1%1%2 day stroke2 day strokeriskrisk

HighHighIntermediateIntermediateLowLowRiskRiskStratificationStratification

6-76-74-54-50-30-3ABCDABCD22

ScoreScore

Low Risk-Low Risk- Outpatient Evaluation Outpatient Evaluation

Intermediate Risk-Intermediate Risk- Inpatient, Hospital Observation, or Outpatient Evaluation Inpatient, Hospital Observation, or Outpatient Evaluation

High Risk-High Risk- Hospitalize Hospitalize

Day after hospitalization she wakesDay after hospitalization she wakesfrom nap with right from nap with right hemiplegia hemiplegia andandaphasiaaphasia–– Last documented normal at noonLast documented normal at noon

Nurse calls the physician listed onNurse calls the physician listed onadmission orders.admission orders.–– No answer after three attempts.No answer after three attempts.–– Nursing eventually determines the correctNursing eventually determines the correct

physician to call.physician to call.

Physician evaluates and orders non-Physician evaluates and orders non-contrast head CTcontrast head CT

4:00 pm4:00 pm

4:30 pm4:30 pm

4:40 pm4:40 pm

Case Continued

Head CT read as negative for bleed.Head CT read as negative for bleed.Based on continued symptomsBased on continued symptoms–– Neurology called for consultation.Neurology called for consultation.

Neurologist explains that she isNeurologist explains that she iscovering multiple hospitals and can notcovering multiple hospitals and can notphysically see the patient.physically see the patient.–– Recommends MRI with diffusion.Recommends MRI with diffusion.

MRI/MRA orderedMRI/MRA ordered

5:005:00

5:105:10

5:155:15

Radiology indicates MRI no longerRadiology indicates MRI no longeravailable as technician has goneavailable as technician has gonehome.home.

Changed to CT perfusion /CTAChanged to CT perfusion /CTA

Read as L MCA clot withRead as L MCA clot withdownstream infarctdownstream infarct

5:205:20

5:255:25

5:455:45

Did this represent exceptional care, standard care, orDid this represent exceptional care, standard care, orsub-standard care?sub-standard care?

TreatmentTreatment

Time ThresholdsTime Thresholds–– Previously 3 hours for IV thrombolysisPreviously 3 hours for IV thrombolysis

ASA now recommends 4.5 hours based on ECASS IIIASA now recommends 4.5 hours based on ECASS III

–– 6 hours for IA thrombolysis6 hours for IA thrombolysis

–– 8 hours for mechanical thrombolysis8 hours for mechanical thrombolysis

1. Del Zoppo GJ et al. Expansion of the Time Window for Treatment of Acute Ischemic Stroke with IV tPA. Stroke 2009;40:2945-482. Adams et al. Early Management of Adults with Ischemic Stroke. Stroke 2007;38:1655-17113. Hacke W, et al. Thrombolysis with Alteplace 3 to 4.5 hrs after Acute Ischemic Stroke. NEJM 2008;359:1317-13294. Lansberg MG et al. Efficacy and Safety of tPA 3 to 4.5 hours after Acute Ischemic Stroke. Stroke 2009;2438-2441

Time to Evaluation for In-HospitalTime to Evaluation for In-HospitalStrokesStrokes

1993 study1993 study–– Median time from recognition to neurologyMedian time from recognition to neurology

evaluation of 2.5 hoursevaluation of 2.5 hours

Albers. Evaluation Times for Patients with In-hospital Strokes. Stroke 1993;24:1817-1822

Admittedly this was 1993Admittedly this was 1993—— prior to the t-PA era prior to the t-PA era

How Are We Doing Now?

Quality of CareQuality of CareEvaluation Time for In-Hospital StrokeEvaluation Time for In-Hospital Stroke

Goal is 25 minutes to CT scanGoal is 25 minutes to CT scan

In the Modern Era:In the Modern Era:

In only 25% was neurology In only 25% was neurology eval eval considered an emergencyconsidered an emergency

Only 15% evaluated by MD within 3 hrs of symptomsOnly 15% evaluated by MD within 3 hrs of symptoms

Only 3% of pts received imaging within benchmark 25 minOnly 3% of pts received imaging within benchmark 25 min

1. Dulli D. Neuroepidemiology 20072. Alvaro LC.. Neurologia 20083. Farooq MU. Cerebrovasc Dis 2008

Education of all staff on stroke symptomsEducation of all staff on stroke symptoms

Any staff member can trigger a stroke alertAny staff member can trigger a stroke alert

Single alert numberSingle alert number

Rapid mobilization of staffRapid mobilization of staff–– Acute Stroke Team or stroke trained Rapid Response TeamAcute Stroke Team or stroke trained Rapid Response Team–– Authority to proceed with evaluationAuthority to proceed with evaluation

Inpatient Inpatient ““Stroke AlertStroke Alert”” Program Program““Code GrayCode Gray””

““Code StrokeCode Stroke””““Code Code NeuroNeuro””

““Code Brain AttackCode Brain Attack””

1. Nolan S. Crit Care Nurs Q 2003

Improving Hospital ProcessesImproving Hospital ProcessesIn-hospital Stroke Evaluation TeamIn-hospital Stroke Evaluation Team

271

74

0

50

100

150

200

250

300

Minutes

Year Before Intervention Year After Intervention

Evaluation Time for In-hospital Ischemic Strokes

1. Cumbler EC. J Stroke and Cerebrovasc Dis in press

Our Patient Has now SufferedOur Patient Has now Sufferedan Ischemic Stroke Followingan Ischemic Stroke Following

Her TIAHer TIA

How can we reduce the chance ofHow can we reduce the chance ofcomplications which would riskcomplications which would risksurvival and promote disability?survival and promote disability?

Management of Co-morbiditiesManagement of Co-morbiditiesGlycemic ControlGlycemic Control

Hyperglycemia present inHyperglycemia present in1/3 of strokes1/3 of strokes

Correlates with worsenedCorrelates with worsenedoutcomesoutcomes

Recommendation is toRecommendation is tocontrol to <200 with goalcontrol to <200 with goalof 80-140of 80-140

How to achieve this goalHow to achieve this goaland whether intensiveand whether intensiveinsulin drip therapy willinsulin drip therapy willend up proving beneficialend up proving beneficialis not clearis not clear

PEARLSPEARLSRarely a need forRarely a need fordextrose in IVF in the firstdextrose in IVF in the first24 hours24 hours

Metformin Metformin problematic-problematic-contrast/lactic acidosiscontrast/lactic acidosis

Sulfonylurea medicationsSulfonylurea medicationsassociated withassociated withhypoglycemia when oralhypoglycemia when oralintake interruptedintake interrupted

MManagement of Co-morbiditiesanagement of Co-morbiditiesHypertensionHypertension

Ischemic PenumbraIschemic PenumbraZone of at risk tissue susceptible to reductionZone of at risk tissue susceptible to reductionbelow the threshold of viability in response tobelow the threshold of viability in response torelatively small drops in MAP.relatively small drops in MAP.

Objective ofObjective ofBlood Pressure ControlBlood Pressure Control

MaximizeMaximizeperfusion toperfusion tothe ischemicthe ischemicpenumbrapenumbra

Minimize theMinimize thehypertensivehypertensiverisk ofrisk ofhemorrhagichemorrhagictransformation.transformation.

Management of Co-morbiditiesManagement of Co-morbiditiesAcute Blood Pressure ControlAcute Blood Pressure Control

80% of stroke admissions have elevated BP.80% of stroke admissions have elevated BP.

Even without intervention, the pressure tendsEven without intervention, the pressure tendsto fall 10-15% in the first 24 hours.to fall 10-15% in the first 24 hours.

By day 10 BP will fall 13-20%By day 10 BP will fall 13-20%

Ischemic Stroke Pre-tPAIschemic Stroke Pre-tPA

Recommended Steps:Recommended Steps:

LabetalolLabetalol 10-20mg IV 10-20mg IV

(may repeat x1) or(may repeat x1) or

NitropasteNitropaste 1-2 inches 1-2 inches

BP must be <185/110 for tPA.

Post-Post-tPAtPA

Monitor BP closely.Monitor BP closely.

BP q15min x 2 hrs thenBP q15min x 2 hrs then

q30min x 6 hrs then q30min x 6 hrs then

qhr x 16 hrs qhr x 16 hrs

Goal BP<180/105

About 1/3 of patients who receive tPA require antihypertensive therapy in the first day.

Choice of agent?NitroprussideLabetololNicardipineFenoldopanNitroglycerin

Avoid sublingual nifedipine and clonidine

Ischemic Stoke Without tPAIschemic Stoke Without tPA

TitratableTitratable

Avoid overcorrectionAvoid overcorrection

If BP lowered it is generally safe as longIf BP lowered it is generally safe as longas not exceeding 10-15%as not exceeding 10-15%

Withhold treatment until BP >220/120

Blood Pressure

““Permissive HypertensionPermissive Hypertension””

Lower targets being investigatedTiming of initiation of antihypertensive therapy controversial

Potter J et al. Controlling hypertension and hypotension immediately post-stroke (CHHIPS) Lancet Neurology 2009;8:48-56

Chronic Blood PressureChronic Blood PressureControlControl

UK TIA study demonstrated a 28%UK TIA study demonstrated a 28%decrease in long term stroke risk fordecrease in long term stroke risk forevery 10mm drop in systolic BP.every 10mm drop in systolic BP.

By comparison- How much riskBy comparison- How much riskreduction do you get with aspirin?reduction do you get with aspirin?

15%15%

ComplicationsComplications64% of stroke patients in a modern stroke64% of stroke patients in a modern strokeunit have a complication in the first weekunit have a complication in the first week–– Fever 24%Fever 24%

–– UTI 16%UTI 16%

–– Pneumonia 11%Pneumonia 11%

–– Myocardial injury 16%Myocardial injury 16%

–– PE 0.6%PE 0.6%

Urinary Tract InfectionUrinary Tract Infection

80% of 80% of nosocomial UTIs nosocomial UTIs are associated withare associated withcatheterscatheters

Infection is directly related to duration of useInfection is directly related to duration of use

Remove ASAP/use alternatives if possibleRemove ASAP/use alternatives if possible

Physicians unaware of catheterPhysicians unaware of catheter–– 28% of cases28% of cases

Aspiration PneumoniaAspiration Pneumonia

__ to > to >__ of stroke patients have dysphagia of stroke patients have dysphagia

One third of patients with aspiration will developOne third of patients with aspiration will developpneumoniapneumonia

50% reduction in risk with formal program:50% reduction in risk with formal program:

Swallow screen prior to diet/medsSwallow screen prior to diet/meds

Aspiration precautionsAspiration precautions

Oral careOral care

Pneumonia/Influenza vaccinePneumonia/Influenza vaccine

Deep Venous ThrombosisDeep Venous Thrombosis

Without prophylaxis, up to 75% of patientsWithout prophylaxis, up to 75% of patientswith hemiplegic stroke will have evidence ofwith hemiplegic stroke will have evidence ofDVTDVT

Effective prophylaxis can reduce the VTEEffective prophylaxis can reduce the VTErate by 50-70%rate by 50-70%

With prophylaxis- 1% symptomatic VTE rateWith prophylaxis- 1% symptomatic VTE rateSherman DG et al. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL study): an open-label randomized comparison. Lancet 2007;369:1347-1355Sherman DG, Prevention of Venous Thromboembolism, Recurrent Stroke, And Other Vascular Events After Acute Ischemic Stroke: The role of Low-Molecular-Weight Heparin and Antiplatelet Therapy. Journal of Stroke and Cerebrovascular disease 2006;15:250-259

Deep Venous ThrombosisDeep Venous ThrombosisStockings and Stockings and SCDsSCDs- non-significant reduction- non-significant reduction

Anti-platelet therapy alone is NOT sufficient Anti-platelet therapy alone is NOT sufficient

Lower potency heparin prophylaxis (heparinLower potency heparin prophylaxis (heparin5000 U bid) less effective than higher potency5000 U bid) less effective than higher potency

Higher efficacy prophylaxis does not appear toHigher efficacy prophylaxis does not appear toconfer increased risk for ICHconfer increased risk for ICH–– Studies have mixed results on this issueStudies have mixed results on this issue

Mazzone C, et al. Physical Methods for Preventing Deep Vein Thrombosis in Stroke. Cochr Database Syst Review 2004;(4):CD001922.

Vergouwen MD et al. Venous Thromboembolism prophlaxis and Treatment in Patients with Acute Stroke and Traumatic Brain Injury. Curr Opin Crit Care2008;14:149-155

Sherman DG. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolismafter acute ischaemic stroke (PREVAIL study): an open-label randomized comparison. Lancet 2007;369:1347-1355http://www.jointcommission.org/NR/rdonlyres/C9A8B113-070E-4AA0-8FB6-8EF50EB02406/0/F_Section4.pdf

Work-up reveals:Work-up reveals:-LDL 120-LDL 120

-Sinus rhythm-Sinus rhythm-Heart structures normal-Heart structures normal

- <50% - <50% stenosis stenosis of both carotidsof both carotids

Non-Non-cardioembolic cardioembolic strokestrokeoccurring on aspirin 81 mg/dayoccurring on aspirin 81 mg/day

How do we optimize herHow do we optimize herchances of avoiding anotherchances of avoiding another

stroke?stroke?

Lipid ManagementLipid Management

SPARCL trial 16% RRR withSPARCL trial 16% RRR withstatin statin over 5 yrs following CVAover 5 yrs following CVA

No change in mortalityNo change in mortality

Small increase in hemorrhagicSmall increase in hemorrhagicstrokes*.strokes*.

High-dose, high-potencyHigh-dose, high-potencycholesterol lowering therapycholesterol lowering therapyrecommended for LDL>100recommended for LDL>100–– Optional goal of <70Optional goal of <70

Secondary PreventionSecondary PreventionAnti-thrombotics-101Anti-thrombotics-101

JCAHO requires anti-thrombotics to beJCAHO requires anti-thrombotics to bestarted within 48 hoursstarted within 48 hours

Warfarin for atrial fibrillationWarfarin for atrial fibrillation

Antiplatelet therapy if non-cardioembolicAntiplatelet therapy if non-cardioembolic–– ClopidogrelClopidogrel

–– ASA/ASA/Dipyridamole Dipyridamole ERER

–– ASAASA

PRoFESSPRoFESSNo difference in strokesNo difference in strokesbetween between Clopidogrel vsClopidogrel vsASA/ASA/DipyridamoleDipyridamole

–– Increased hemorrhage inIncreased hemorrhage inASA/ER-ASA/ER-DipyriamoleDipyriamole

–– Clopidogrel Clopidogrel better toleratedbetter tolerated

Secondary PreventionSecondary PreventionAnti-thrombotics-201Anti-thrombotics-201

Acute use of heparin has never been proven toAcute use of heparin has never been proven toimprove outcomes.improve outcomes.–– early second ischemic stroke equally balanced byearly second ischemic stroke equally balanced by early hemorrhagic strokes early hemorrhagic strokes

Higher doses of aspirin do not provide greaterHigher doses of aspirin do not provide greaterbenefit than low doses- benefit than low doses- UK TIA trialUK TIA trial

For arterial strokes- For arterial strokes- warfarin warfarin is not superior tois not superior toaspirin- aspirin- WARSS TrialWARSS Trial

Combination of Combination of clopidogrel clopidogrel and aspirin does notand aspirin does notprovide benefit over provide benefit over monotherapymonotherapy- - MATCH TrialMATCH Trial