cva overview ron barac, do internal medicine lecture series millcreek community hospital april 16,...

CVA OVERVIEWCVA OVERVIEW

Ron Barac, DOInternal Medicine Lecture SeriesMillcreek Community Hospital

April 16, 2008

Emergency Evaluation of Strokefirst 15 minutes

ABCs Document Hx & PE – Especially time last known to be normal – NOT when symptoms first noted…. Blood work (CBC, CMP, INR/PT/PTT) EKG, CXR Send for brain imaging Consult Neurology

Stroke in the U.S.Stroke in the U.S.

750,000 new strokes annually Mortality rate 20-25% Leading cause of long term disability in

adults Economic impact - $40 billion in health

care costs and lost productivity Personal impact - patient and family

Stroke SubtypesStroke Subtypes

S troke

Large A rteryA therosc leros is

S m all V esselD isease

(lacunar in farc tion)

C ard ioem bolism O ther

Ischem ic S troke - 80% H em orrhagic S troke - 20% Intracerebral hem orrhage Subarachnoid hem orrage

TIATIA

A stroke-like deficit that resolves in under 24 hrs

80% resolve within 60 minutes– Median duration is 14 minutes

Event Risk Within 3 MonthsEvent Risk Within 3 MonthsAfter TIAAfter TIA

Johnston SC, et al. JAMA. 2000;284:2901 2906.

RecurrentTIA

Cardiac Event

Stroke Death

Eve

nt R

ate

12.7%

2.6% 2.6%

10.5%

5% in 48 hrs

• age > 60 years

• diabetes mellitus

• duration of episode greater than 10 min

• weakness and speech impairment with the episode

Independent risk factors for stroke within 90 days after TIA:

Non-Modifiable Risk FactorsNon-Modifiable Risk Factors

Age Race ( African-American, Hispanic ) Sex ( male > female ) Family history, genetic components

Primary PreventionPrimary Prevention

HTN (both systolic and diastolic and isolated systolic)

Atrial Fibrillation– warfarin

INR goal 2.0 - 3.0 reduces ischemic events by approx. 65%

Primary PreventionPrimary Prevention

Atrial Fibrillation– aspirin

for “low risk” patients reduces ischemic events by approx. 20% low dose warfarin plus aspirin not as effective as

adjusted dose warfarin

Primary PreventionPrimary Prevention

Other Cardiac Conditions– valvular disease– post-MI survivors– HF, LVH, etc.

Primary PreventionPrimary Prevention

Diabetes Mellitus Hyperlipidemia

– Statins prevent stroke in DM regardless of the presence of vascular dz. (even with normal cholesterol)

– Statins recommended for primary prevention in patients with CAD; goal <70 in very high risk patients

Primary PreventionPrimary Prevention

Carotid Artery Disease (asymptomatic)– consider CEA for stenoses > 60%

Carotid Angioplasty and Stenting– should be reserved for high risk patients failing

best medical management; should only be done by rigorously qualified providers

Primary PreventionPrimary Prevention

Smoking Cessation Alcohol Intake

– mild / moderate intake may be beneficial– excessive intake detrimental

Exercise and weight loss OCP’s + Smoking

Primary PreventionPrimary Prevention

Treatment of sleep-related breathing disorders

Cessation of cocaine use Dietary changes (Mediterranean diet) ACE inhibitors ( HOPE trial ) Angiotensin receptor blockers Treatment of metabolic syndrome

Secondary PreventionSecondary Prevention

Aspirin– optimal dose – ( 50 to 325 mg ) no clear

evidence that high or moderate dose is better than low dose

– only antiplatelet agent proven in acute setting (for stroke); give within 48 hours

– approximately 22 % risk reduction

Secondary PreventionSecondary Prevention

Aggrenox (ASA 25 mg + extended-release dipyridamole 200mg)– superior to ASA alone ( 37% risk reduction c/w

placebo, 23 % c/w ASA)– 7th ACCP conference recommends it (or Plavix)

be used first-line instead of ASA for non-cardio embolic stroke or TIA

Time in Months

ESPS 2: Primary Outcome

Reprinted from the Journal of the Neurological Sciences, Vol 151 (suppl), ESPS 2 Group, European Stroke Prevention Study 2, Efficacy and safety data, S1-S77, 1997, with permission from Elsevier. .

Survival Curves for Fatal and Nonfatal Stroke

0 6 12 18 24

Su

rviv

al P

rob

abil

ity

0.750

0.800

0.850

0.900

0.950

1.000

Placebo

ASA

ER-DP

ASA/ER-DP

ESPS 2: SummaryESPS 2: Summary

• ASA/ER DP is about twice as effective as aspirin alone in secondary stroke prevention1

• There was a 20% relative risk reduction in the secondary endpoint stroke/MI/ vascular death with ASA/ER DP vs. aspirin2

• Bleeding rate of the combination of ASA/ER DP is comparable to aspirin alone1

• In a post hoc analysis, no increase in cardiac events was reported with ASA/ER DP3

1. ESPS 2 Group. J Neurol Sci. 1997;151(suppl):S1 S77.2. Data on file, Boehringer Ingelheim Pharmaceuticals, Inc. 3. Diener HC, et al. Int J Clin Pract. 2001;55:162 163.

Secondary PreventionSecondary Prevention

Plavix (Clopidogrel) Reduces combined risk of stroke, MI and

vascular death in patients with atherosclerotic vascular disease– relative risk reduction vs. ASA - 8.7%– stroke + death rate may be same as ASA– less side effects vs. ticlopidine

Secondary PreventionSecondary Prevention

Plavix plus ASA (MATCH trial)– benefit of combination over Plavix alone

cancelled out by excess bleeding present– validity of results questioned due to the paucity

of large artery atherosclerosis represented

CAPRIE and MATCH: SummaryCAPRIE and MATCH: SummaryCAPRIE 1 MATCH 2

Comparator Clopidogrel vs. aspirin Clopidogrel + aspirin vs. clopidogrel

Patients 1/3 stroke, 1/3 MI, 1/3 PAD 79% stroke, 21% TIA

Primary outcome

Vascular death, non fatal MI, or stroke

Ischemic stroke, MI, vascular death, or re-hospitalization

Result The combined patient population showed a slight but significant benefit of clopidogrel over aspirin.

Individual patient group analysis showed no significant benefit of clopidogrel over aspirin in MI or stroke patients.

There was no significant difference in efficacy of combination therapy (clopidogrel + aspirin) compared with clopidogrel alone.

Significant increase in life- threatening and major bleeding in combination clopidogrel + aspirin therapy compared with clopidogrel alone.

1. CAPRIE Steering Committee. Lancet. 1996;348:1329 1339. 2. MATCH trial. Lancet. 2004;364:331 337.

Secondary PreventionSecondary Prevention

Ticlopidine (Ticlid)– relative risk reduction vs. ASA - 10%– possibly greater benefit in women, patients with

completed stroke or vertebrobasilar ischemia– 2% incidence of neutropenia

Secondary PreventionSecondary Prevention

Warfarin (Coumadin)– atrial fibrillation– post-MI ventricular thrombus– valvular disease– ? antiplatelet treatment failure ( benefit over

ASA not apparent in noncardioembolic disease- WARS study)

Secondary PreventionSecondary Prevention

ACE inhibitors + diuretics ( PROGRESS trial )– Perindopril ( Aceon ) + indapamide ( Lozol )-

47 % risk reduction PRoFESS trial

– comparing Aggrenox vs Plavix– ongoing

Secondary PreventionSecondary Prevention

Carotid Endarterectomy ( for symptomatic stenosis )– CEA for men with stenosis > 50% and women

with stenosis > 70% if 30 day operative morbidity / mortality < 6%

– Benefit lost with significant delay to surgery

Secondary PreventionSecondary Prevention

Angioplasty and Stenting– CREST trial-carotid stent=CEA for high risk

symptomatic patients >70%– use for symptomatic intracranial disease should

be evaluated on a case by case basis, and should be performed by rigorously qualified providers

Acute Stroke ManagementAcute Stroke Management

Stroke Alert ( TIME IS BRAIN ! ) Acute Diagnosis

– clinical level of consciousness location of stroke severity of stroke - NIH stroke scale

ABC’s

Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization

Left MCA-aphasia, R hemiparesis ( face & arm > leg ), +/- visual field defect, gaze palsy, sensory loss

Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization

Right MCA-L hemiparesis, +/- visual field defect, gaze palsy, sensory loss

Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization

PCA-contralateral visual loss, confusion, +/- aphasia

Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization

ACA-contralateral leg weakness and numbness, incontinence

Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization

PICA-ipsilateral facial & contralateral body sensory loss, dysarthria, ataxia, vertigo, ipsilateral Horner syndrome

Acute Stroke ManagementAcute Stroke ManagementLocalizationLocalization

VB-some combination of ataxia, vertigo, N/V, weakness, diplopia, dysarthria, coma

Acute Stroke ManagementAcute Stroke Management

Acute Diagnosis– clinical

remember differential diagnosis - trauma, CNS infection, seizure, hypertensive encephalopathy, mass lesion, migraine, metabolic, toxic

– radiologic noncontrast CT MRI/MRA ( diffusion/perfusion ) CT angiography

Acute Stroke ManagementAcute Stroke Management

Acute Medical Assessment – cardiac dysrhythmias ( EKG )– peripheral vascular assessment– r/o trauma in comatose patients– r/o metabolic problems and overdose– r/o hypoxemia, anemia, CHF

Acute Stroke ManagementAcute Stroke Management

Acute Treatment - General– positioning - head of bed flat or nearly flat– ? supplemental oxygen

Acute Stroke ManagementAcute Stroke Management

Acute Treatment - General– fluid management

1/3 of stroke patients dehydrated glucose-containing solutions worsen ischemic

damage normal saline - fluid of choice; consider bolus 10-

15cc/kg consider colloid administration (albumin) less aggressive fluid resuscitation after first 24 hours

Acute Stroke ManagementAcute Stroke Management

Acute Treatment - General– NPO– aggressive treatment of hyperthermia– treatment of hyper/hypoglycemia– aspiration precautions– DVT prophylaxis

Acute Stroke ManagementAcute Stroke Management

Acute Treatment - General– GI prophylaxis– aggressive treatment of seizures– thiamine if EtOH or malnourished– ASA– ? heparin - unproven

Acute Stroke ManagementAcute Stroke Management

Acute Treatment - General – blood pressure management

thrombolytic candidates: BP < 185/110 non-thrombolytic candidates:

– BP < 220/120; MABP < 130

– treat if aortic dissection, MI, CHF, hypertensive encephalopathy

Acute Stroke ManagementAcute Stroke Management

Acute Treatment - General– blood pressure management

drugs of choice– nitropaste - 1 to 2 inches

– labetolol - 10 to 20 mg IV (drip 2 - 8 mg/min.)

– enalapril - 1.25 mg IV

– nicardipine – 5 to 15 mg IV/hour

– nitroprusside (if severe) - 0.5 ug/kg/min. IV

Acute Stroke ManagementAcute Stroke Management

Acute Treatment - General– blood pressure management

hemorrhagic stroke - ? more aggressive management

– frequent neuro checks and vitals - emergent CT if neuro change

Acute Stroke ManagementAcute Stroke Management

Acute Treatment - General– cardiac monitoring – treat anemia, hyponatremia, hypomagnesemia

Acute Stroke ManagementAcute Stroke Management

Subsequent Treatment– mobilize after 24 hours ( if neuro stable )– early PT / OT / speech therapy / stroke ed.– aspiration precautions– strict I’s and O’s

Acute Stroke ManagementAcute Stroke Management Subsequent Treatment

– prevention / treatment of cerebral edema oncodiuretic therapy ( albumin + lasix ) elevate head of bed avoid fever, hyponatremia, seizures, hyperglycemia,

hypotonic IVF hyperventilation - pCO2 25 to 30 mannitol (0.5 to 2 g / kg IV) glycerol 250 cc of 10% solution q 6 hrs. administration of hypertonic saline ICP - monitoring; barbiturate anesthesia hemicraniectomy and durectomy

Evaluation (Risk Stratification)Evaluation (Risk Stratification)

Precise anatomic and etiopathogenic assessment helps define prognosis and tailor secondary prevention

Imaging of brain parenchyma– non-contrast CT– MRI ( diffusion-weighted imaging, etc. )

Evaluation (Risk Stratification)Evaluation (Risk Stratification)

Intracranial vascular assessment– MRA– CT angiography

Evaluation (Risk Stratification)Evaluation (Risk Stratification)

Extracranial vascular assessment– color Doppler and B-mode ultrasound– MRA– CT angiography

Evaluation (Risk Stratification)Evaluation (Risk Stratification)

Cardiac assessment– TEE (aortic arch, atria, valves, ventricles)– TTE - may be of little value unless abnormal– EKG and cardiac exam

Evaluation (Risk Stratification)Evaluation (Risk Stratification)

Serologic assessment– lipid profile– ESR, CBC, PT, PTT– hypercoagulability work-up: protein C, protein

S, lupus anticoagulant, anticardiolipin antibody, anti-thrombin III, Factor V Leiden, homocysteine, ? fibrinogen, ? prothrombin gene mutation, ANA

Evaluation (Risk Stratification)Evaluation (Risk Stratification)

Serologic assessment– sickle cell screen– consider paraprotein search or neoplastic

search– consider illicit drugs

Urgent InterventionUrgent Intervention

Reperfusion Neuroprotection

Urgent Intervention - Urgent Intervention - ReperfusionReperfusion

Aspirin Intravenous t-PA Intra-arterial Prourokinase Ancrod Other (non-pharmacologic) interventions

- supportive care

- carotid endarterectomy ( for TIA )

- angioplasty/stent

AspirinAspirin

Decreases mortality when given within the first 6 hours (MAST-I)

May improve stroke outcome w/o significant risk of hemorrhage

May have some utility as hyperacute therapy in the field

Recommended to be given within 48 hours

t-PA (NINDS, NEJM Dec, 1995)t-PA (NINDS, NEJM Dec, 1995)

Placebo controlled, multi-center Treatment within 3 hours of onset Dose: 0.9mg/kg Part 1 (291 patients); Part 2 (333 patients) Patients receiving t-PA 30% more likely to have

minimal or no disability at 3 months Symptomatic ICH in 6.4% (0.6% placebo) Serious systemic hemorrhage in 1.6% (0% placebo) Minor external bleeding in 23% (3% placebo)

t-PA (Update)t-PA (Update)

Age >80 no longer excluded No benefit beyond 3 hour window(ECASS, ATLANTIS) Trend toward better outcome with

earlier treatment Up to 20% of patients may be

candidates with aggressive approach

ANCROD ANCROD Venom of the Malaysian pit viper Indirect acceleration of endogenous fibrinolysis 3 hour window, 3 day infusion, 500 patients Requires fibrinogen monitoring (40-70) Positive benefit at 90 days Symptomatic ICH in 5.2% ( 2% placebo ) FDA approval pending

ProurokinaseProurokinase

Intra-arterial administration in patients with MCA occlusion

6 hour window, 3 hour infusion followed by 4 hour infusion of low-dose heparin

180 patients Positive benefit at 90 days (67% with recanalization) Increased rate of symptomatic ICH but no increase in

mortality FDA approval pending

HeparinHeparin

No large-scale clinical trials have demonstrated efficacy for routine use of intravenous heparin in acute stroke

Some benefit with subcutaneous heparin, possibly based on DVT prophylaxis

Still advocated in selected patients for prevention of recurrent ischemic events

Other uses are still controversial

Urgent Intervention - Urgent Intervention - ReperfusionReperfusion

TIME IS BRAIN Strict adherence to protocol to minimize

risk Patient and family should be informed of

potential risks

t-PA Stroke Protocol - t-PA Stroke Protocol - Inclusion CriteriaInclusion Criteria

Age over 18 Clearly defined time of onset within 3 hours

of treatment Measurable neurological deficit

(NIHSS >4)

t-PA Stroke Protocol - t-PA Stroke Protocol - Exclusion CriteriaExclusion Criteria

Rapid neurological improvement History suggesting SAH SBP >185 or DBP >110 (can have single dose of anti-

hypertensive tx) Increased ptt, PT>14, platelet count <100K Pregnant or lactating female Acute MI or post-MI pericarditis Glucose <50 or >400 Heme + stool CT exclusion (hemorrhage, ? early ischemic change)

t-PA Stroke Protocol - t-PA Stroke Protocol - Exclusion CriteriaExclusion Criteria

Prior stroke or serious head trauma within 3 months Major surgery within 14 days Arterial puncture at noncompressable site or lumbar puncture

within 7 days History of intracranial hemorrhage History of brain tumor, AVM, or aneurysm GI or UT bleeding within 21 days Seizure at stroke onset Warfarin treatment Heparin within 48 hours

t-PA Stroke Protocol - t-PA Stroke Protocol - TreatmentTreatment

t-PA at 0.9mg/kg ( max 90 mg )

- 10% bolus

- 90% as continuous infusion over 60 min No anti-coagulant or anti-platelet agents for 24

hours after treatment ( repeat CT ) BP maintained SBP<180 and DBP<105 Patients must be monitored closely for

neurological deterioration