Medical Management of Stroke

Stroke Code!

• Rapid Assessment. (NIH Stroke Scale)• Non-con CT• CTA/CTP• Call Duty Neurologist• Is patient t-PA candidate?

– Or candidate for other acute therapies?

• See Neurology Sharepoint for Stroke Protocols• Stroke registry• Stroke review meetings

Stroke Definitions

• Focal Neurologic

• Negative Symptoms

• Vascular Origin

• Sudden Onset

• Sudden Headache (SAH)

Cerebral Blood Flow

• Normal CBF 50 – 55 ml/100gm/min• About 18 - 20 ml/100gm/min – Failure of neuronal

function• About 8 -10 ml/100gm/min – cellular death

• Hypoperfused area = ischemic penumbra

• Restore perfusion to ischemic penumbra• Protect neurons until perfusion restored

• Rapid Diagnosis and intervention

Transient Ischemic Attack

• < 24 hours by definition• Most last 10 – 20 minutes• Warning sign of Stroke: like unstable

angina and MI• Expedite work-up• Typically present with rapid-onset deficits

maximal at onset.• Compare with “march” of Migraine or

Seizure

Signs of TIA

• Anterior circulation– Aphasia, neglect, Amaurosis, isolated leg

weakeness, abulia

• Posterior circulation– Diplopia, ataxia, dysphagia,hiccups, vertigo,

crossed signs

• Either– Hemiplegia, visual field cuts, hemisensory

loss, dysarthria

TIA evaluation

• Carotid imaging

• Intracranial vessel imaging

• Cardiac source eval

TIA Rx

• CEA for symptomatic Carotid Stenosis >70%– Stenting, if surgical contraindications

• Cardiac source: Coumadin. ASA if not able to give coumadin.

• Atherosclerosis: ASA, Statins, Clopidogrel. ASA + dipyridimole

• Lacunar: ~ Same. Antihypertensive Rx.

MATCH Trial• Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient

Ischemic Attack (MATCH) study,– Clopidogrel + aspirin for secondary prevention of stroke

• The efficacy of any antiplatelet therapy, including aspirin, is modest when it is used as monotherapy, and combination therapy with 2 antiplatelet agents has shown promise in reducing the risk for secondary stroke in patients who have had a previous transient ischemic attack (TIA) or ischemic stroke.

• MATCH trial indicated that the reduction in risk achieved by adding aspirin to clopidogrel is not significantly greater than that achieved with clopidogrel alone.

• Significant increase in life-threatening bleeding complications was associated with the combination of clopidogrel + aspirin.

• Clopidogrel + aspirin cannot be recommended at this time for the secondary prevention of stroke in patients who have had a previous ischemic stroke or TIA.

• (? 3 month short term Rx after ominous stroke)

• From American Journal of Medicine

ESPS-2

• Second European Stroke Prevention Study (ESPS-2)

• Demonstrated a significant reduction in risk for secondary stroke with aspirin + extended-release dipyridamole versus aspirin alone

PRoFESS Trial(Full results yet to be published)

• Prevention Regimen for Effectively avoiding Second Strokes.

• Plavix (clopidogrel) ~= Aggrenox (ASA + DP)

• (Micardis not better than Placebo)

CT scan of early stroke

Types of Stroke

• Ischemic– Arterial– Venous

• Headache, lethargy, Seizure

• Hemorrhagic– Intra-parenchymal– Sub-arachnoid

Stroke etiologies

Stroke risks

Ischemic Stroke

• Destructive cascade induced by ischemia

• Decreased O2 and glucose – ATP insufficiency– Ca++ influx– Increase Glutamate– Membrane degradation– Free radical increase– Apotosis

Large MCA Stroke

Sources of stroke

Stroke Syndromes

• Carotid– ACA: Leg > Arm, Frontal lobe symptoms– MCA: Face, Arm > Leg; gaze preference,

Aphasia, hemineglect etc

• Vertebrobasilar– PCA: Hemianopsia, etc– Brain stem Stroke: Crossed signs, diplopia,

vertigo, dysphagia, Horner’s Syndrome, etc

Right PICA stroke

Lacunar Syndromes

• Pure Motor

• Pure Sensory

• Sensorimotor

• Ataxia-hemiparesis

• Dysarthria Clumsy Hand

• Hemichorea

Arteriopathies

• Atherosclerosis• Non-Atherosclerotic

– Inflamatory• Angiitis• GCA• Syphilis etc

– Non-inflamatory• Dissection• FMD• Moya Moya• Homocysteinuria • CADASIL

– cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

• Drugs etc

Stroke Risk Factors

• Age• Race• Gender• Family History• Prior Stroke

• HTN• DM• Heart Disease• Smoking• Hyperlipidemia• Carotid bruits• Excessive EtOH• BCP• Obesity and inactivity

Embolic Stroke

• High Risk vs Low Risk Cardiac sources

Hematological Diseases

• Antiphospholipid Antibody Syndrome

• Protein C deficiency

• Protien S deficiency

• Factor V Leiden

• Other hypercoagulable states

Venous Ischemic Stroke

• Post partum

• Hypercoagulable States

• Infections

• Dehydration

• Tumors

• Post-op

Hemorrhagic Strokes

• Hypertensive– Putamen– Thalamus– Cerebellar– Pontine

• Aneurysmal

• AVM

• Amyloid Angiopathy

Stroke Rx decision tree

Ischemic Stroke Strategies

• “Time is Brain”

• Reperfusion• Ancillary Care

– Systemic– Avoid Complications

• Neuro-protection• Secondary Prevention

– Anti-platelet agents– Statins– Hypertension Rx– Smoking cessation– Weight Control

Initial Stabilization and Monitoring

• Assess airway maintenance

• Level of Arousal

• Evaluation for MI

• Dysrhythmia monitoring

Diagnostic Eval for Stroke

• Urgent, for all: CT or MRI, Electrolytes, glucose, BUN, Creatinine, CBC, PT/PTT, O2 Sat

• Urgent, for some: Tox screen, Blood alcohol, LFTs, HCG, CXR, ABG, LP, EEG

• Non-urgent, for etiologic eval: TEE or TTE, Carotid Doppler, MR angiogram, CT angiogram, Catheter angiogram, RPR, ESR, homocysteine, lipids.

• Selected patient eval: Coag panel, TSH, MR imaging and MRA of intracranial vessels

Stroke Rx

• Anticoagulation ~doesn’t benefit• Consider anticoagulation

– Known large vessel disease with fluctuating symptoms– Mechanical Heart valves– LV Thrombus– Prothrombotic states– Cerebral Venous Thrombosis

• Prone to Hemorrhage:– Large infarcts– Extensive Occipital Lobe involvement– Early Petechial Conversion– Uncontolled hypertension, Hyperglycemia

Stroke Rx

• Induced hypertension might help salvage ischemic Penumbra

• Double edge sword

Fluid management

• May need to be NPO

• Avoid hypotonic solutions if risk of cerebral edema

• Monitor electrolytes

• Prevent hyperglycemia – leads to worse outcome

Prevent Complications

• DVT prophylaxis– Pneumatic compression stockings– SQ Low Molecular Weight Heparin

• GI Prophylaxis

• Feeding

• Chest PT/positioning

• Stool softeners

• Prevent infection - UTI

MRIs before and after t-PA

Thrombolytic Therapy

• Goal – preserve ischemic penumbra• 3 hour window for IV t-PA

– 6% bleed.– Outcome: 12 % > placebo

• Intra-arterial t-PA – not FDA approved – “investigational”, 6 hour window.

• Abciximab – disappointing result• ASA acute Rx – some value• Hypothermia – shows promise, but technically

difficult• “Merci” clot retriever – FDA approved

Absolute contraindications to t-PA

• Presenting symptoms and signs should not suggest acute subarachnoid hemorrhage

• Head trauma or prior stroke within the previous 3 months• Myocardial infarction within the previous 3 months• Gastrointestinal or urinary tract hemorrhage within the previous 21

days• Major surgery within the previous 14 days• Arterial puncture at a noncompressible site within the previous 7

days• History of previous intracranial hemorrhage• Active bleeding or acute trauma (fracture) on examination• Platelet count <100,000 mm3 • Blood glucose <50 mg/dL• Seizure or postictal neurologic impairments

Relative contraindications to t-PA

• Oral anticoagulation (international normalized ratio must be ≤1.5)

• Heparin within the previous 48 hours (activated partial thromboplastin time must be in the normal range)

Stroke with hemorrhage s/p t-PA

Protocol for thrombolytic therapy in patients with of

acute ischemic stroke • 1. Determine if the patient is a candidate for thrombolytic therapy.

• 2. Infuse alteplase (rt-PA) 0.9 mg/kg (maximum of 90 mg) over 60 minutes with 10% of the dose given as a bolus over 1 minute.

• 3. Admit the patient to an intensive care unit or stroke unit for monitoring.

• 4. Neurologic assessment to be performed every 15 minutes during the infusion of rt-PA and every 30 minutes for the first 2 hours for the next 6 hours, then every hour for 24 hours from the time of initial treatment.

• 5. If the patient develops a severe headache, acute hypertension, nausea, or vomiting, discontinue the infusion and perform and emergency CT brain scan.

• 6. Measure blood pressure every 15 minutes for the first 2 hours, every 30 minutes for the next 6 hours, and then every hour until 24 hours from the time of initial treatment.

• 7. Increase the frequency of blood pressure measurements if a systolic blood pressure ≥180 mm Hg systolic or ≥105 mm Hg diastolic is recorded. Administer antihypertensive medications to maintain the blood pressure at or below these levels

Antihypertensive Rx in acute stroke

• Avoid Rx unless planned thombolysis and SBP > 185 or DBP >110

• Evidence of end organ damage

• Excessively high BP: SBP > 220 ; DBP > 110

• Labetolol or Nicardipine Drip for BP Rx with thombolysis

Antihypertensive RxDrug Mechanism Dose Cautions

Labetolol a-1, b-1, b-2 antagonist

0.5 – 2.0 mcg/min infusion

Bradycardia, Bronchospasm

Esmolol b-1 antagonist 50 -300 mcg/kg/min infusion

Bradycardia, Bronchospasm

Nicardipine CCB 5 -15 mg/ hour infusion

Reflex tachycardia, LV Failure, AS

Fenoldopam DA-1 agonist 0.1 – 0.3 mg/kg/min infusion

Tachycardia, Glaucoma, Liver disease

Nitroprusside Vasodilator 0.25 – 10 mg/kg/min infusion

Increase ICP, N/V, sweating, Toxicity

Vasopressor Rx

Drug Mechanisms Dose Cautions

Phenylephrine a-1 agonist 40 -180 mcg/min Bradycardia or tachycardia, MI

Norepinephrine a-1, b-1 agonist 2 -40 mcg/mim Tachycardia, site necrosis, MI, Sulfa

Dopamine DA -1 agonist

a-1, DA -1 agonist

a-1, b-1, DA-1 agonist

1 -2.5 mcg/kg/min

2.5 –10mcg/kg/min

>10mcg/kg/min

H/A, Tachycardia, CAD, Sulfa

Dobutamine b-1, b-2 agonist 2 – 20 mcg/kg/min Tachycardia, MI, cardiac ectopy

Vasopressin ADH analog 0.01 – 0.1 units/min Arrythmia, MI, seizures, H20 intoxication

Massive stoke with trans-falcine herniation

Cerebral Edema Rx

• First prevention

• Higher risk– Large hemispheric stroke in younger person

(little room to swell)– Cerebellar Stroke– H/o Hypertension

Cerebral Edema Rx

• HOB elevation, Fluid restriction, Treat fever• Hyperventilation – causes vasoconstriction: brief

effect, may get rebound vasodilation, ?worsens ischemia

• Osmotic agents – mannitol vs hypertonic saline vs furosemide

• Barbiturates – decrease cerebral metabolic rate. Not really effective.

• Steroids do not work for cytotoxic stroke edema• Hypothermic Rx?• Hemicranectomy/Surgical Decompression

Large stroke s/p hemicraniectomy

Hemorrhagic Stroke Strategies

• Stop Bleeding

• Ancillary Support

• Neuro-protection

Parenchymal Hemorrhage in Basal Ganglia

Intracerebral Hemorrhage

• May be difficult clinically to distinguish Ichemic Stroke from Hemorrhage

• More likely to be Headache, vomiting, Loss of Consciousness

• CT scan

• Prognosis: size of hematoma, clinical status, age, intraventricular blood.

• ? No ischemic penumbra

Medical Rx of Intracerebral Hemorrhage

• ABCs• Blood Pressure Management• Increased BP may be response to the acute event• Controversy - ?ischemic penumbra• MAP vs SBP

– MAP goal 100 – 120 mm Hg– SBP goal 130 – 160 mm Hg

• Obstuctive hydrocephalus• Surgical evacuation

– Particularly for cerebellar hematoma

• Euvolemia, Euthermia, Normal glucose

Intracranial Pressure

• CPP = MAP – ICP• CPP > 60 mm Hg

• Acute Rx of increase ICP– Raise HOB > 30 degrees– * Hyperventilate to Pco2 of 25 -30 mm Hg– * Diuretics: Lasix– * Mannitol 1gm/Kg IV to get serum osmolarity of 300

– 320 mOsm– * for acutely deteriorating patient– No steroids

Seizure prophylaxis

• Risk highest in first 24 hours

• Risk higher if cortical hemorrhage

• Prophylaxis options– Phenytoin– Fosphenytoin– Valproate

SAH

SAH data

• “Worst headache of my life”• Sentinel Bleeds• ~ 10/100,000 person-years• ~30,000 cases per year in USA• Increased risk with EtOH intake, hypertension, smoking,

1st degree relative with SAH• Prevalence of unrupture intracranial aneurysm about

1%.• SAH - ~80% reach hospital alive, ~30% in-hospital

mortality, ~16% with full recovery without defecits• Outcome predicted by: Neuro status at admission, age,

amount of sub-arachnoid blood.

Hunt-Hess Grading scale for SAH

Grade Criteria

1 Asymptomatic or minimal headache and slight nuchal rigidity

2 Moderate-to-severe headache, nuchal rigidity, no neurologic deficit other than cranial nerve palsy

3 Drowsiness, confusion, or mild focal deficit

4 Stupor, moderate-to-severe focal deficit (hemiparesis); vegetative disturbances

5 Deep coma, decerebrate posturing

SAH Medical Rx

• Early clipping of aneurysms now standard.

• Previously: rebleeding was major cause of mortality and morbidity.

• Now: vasospasm and delayed ischemic deficits are primary concerns.

SAH Medical Rx• ABCs• Pain Control• IV access• Fever control

– “central fever” vs infection• Prevent vasospasm with Nimodipine

– 60mg q4hr po• Seizure prophylaxis• Fluids

– Cerebral salt wasting vs SIADH– Maintain normall intravascular volume

• Hematocrit– 30 -34% is ideal

• Blood Pressure– Rebleeding vs reduced perfusion

• Respiratory– Supplemental Oxygen– DVT prophylaxis

• Bowel care– NPO initial 24 – 48 hrs– Ulcer prophylaxis– Nausea Rx

SAH complications

• Vasospasm

• Cerebral Salt Wasting

• Hydrocephalus

Vasospasm in SAH

• Documented in ~60%, ~ 50% symptomatic• Delayed ischemic deficits in ~16%• Onset about 3 -5 days post-bleed• Peaks 7 – 10 days• Resolves spontaneously over 2 – 4 weeks• Manifest clinically by: decreased responsiveness, abulia,

focal deficits• Transcranial Doppler• “Triple-H therapy”: Hypervolemia, hemodilution,

hypertension. • Angiography suite for Rx

Hyponatremia in SAH

• Hyponatremia in ~30%/

• Cerebral Salt Wasting– Hypovolemia– Natriuresis– Hyponatremia

• Contrast with SIADH

• Volume repletion and maintenance of positive Sodium balance

Hydrocephalus

• Noncomunicating – usually acute• Communicating (non-obstructive) – usually subacute or

delayed.• Signs: decline in alertness, confusion, disorientation,

inattention.• CT scan – enlarged ventricles• Noncommunicating

– Intraventricular catheter to drain CSF• Communicating

– Lumbar drain– Serial LPs– If chronic, ventriculoperitoneal shunt. (About 20% of patients will

require)

JCAHO Performance Measures for Stroke Centers

• 1* Deep Vein Thrombosis (DVT) Prophylaxis  • 2* Discharged on Anti-thrombotics• 3* Patients with Atrial Fibrillation Receiving Anticoagulation

Therapy • 4* Tissue Plasminogen Activator (t-PA) Considered• 5 Anti-thrombotic Medication Within 48 Hours of Hospitalization• 6 Lipid Profile During Hospitalization• 7 Screen for Dysphagia• 8 Stroke Education• 9 Smoking Cessation• 10 A Plan for Rehabiliation was Considered• *Initial standardized stroke measure set• Note:  All ten measures comprise set for pilot testing.