EVIDENCE-BASED PRINCIPLES

OF
STROKE MANAGEMENT

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 Stroke

Hemorrhage
Infarction

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Immediate Diagnostic Studies
All patients Selected patients
 Cranial CT scan  Hepatic function tests
 ECG  Toxicology screen
 Blood glucose  Blood alcohol
 Serum electrolytes determination
 Renal function tests  Pregnancy tests
 CBC + platelet  ABG
 PT + INR  CXR
 aPTT  Lumbar puncture
 EEG

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Cerebral infarction

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Cerebral infarction
 Acute phase
Admission to stroke unit
ABCs
Maintenance of normal physiologic parameters
 Measures to restore circulation
Thrombolysis – within 3 hours of stroke onset
Permissive hypertension
Treatment of Cerebral edema and raised ICP
Antiplatelet and anticoagulant agents
Surgery for symptomatic carotid stenosis

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Cerebral infarction
 Physical Therapy & Rehabilitation
 Measures to prevent stroke
Aspirin vs Anticoagulation
Hypotensive agents
Maintain systemic BP, oxygenation,
intracranial blood flow during surgical
procedures, esp elderly
Lifestyle modification:
○ Discontinue smoking
○ Low cholesterol, low fat diets
Cholesterol lowering agents

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Stroke Units

 This is geographic area within the hospital designated for stroke

and stroke-like patients, who are in need of rehabilitation services
and skilled professional care (by personnel with special interest on
stroke) that such a unit can provide.

M. Dennis and P. Langhorne, BMJ 1994

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 The Stroke Unit - Team

Nurses Medical Doctors Physiotherapists

Occupational Therapists Speech Pathologists

Nutritionists Home Care Case

Managers
Social Workers 8
Stroke Units
 Organized stroke care has been shown to reduce mortality by about 30% and
improve outcome.

 A large number of RCTs have compared care on general medical or other

wards with that in an organized SU & a
meta-analysis has shown a convincing benefit.
Stroke Unit Trialists’ Collaboration 2002.
Cochrane Database Syst Rev 1:CD000197

 Patients treated in a hospital with an acute SU had significantly lower odds

ratio for death of 0.89 (95 % CI 0.85–0.93).
Jarman B, Aylin P, Bottle A..
BMJ 2004;328:369

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Stroke units
 reduced deaths due to secondary complications
 careful and systematic assessment of dysphagia
 reduction in the use of urinary catheters
 more aggressive management of infections
 Programs of early activation and mobilization

 reduce disability (dependency) after stroke

 more coordinated and focused program of rehabilitation involving
patients and caregivers
 more intensive physiotherapy and occupational therapy input
 patient motivation and morale

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General supportive care
 Airway and ventilatory support
 Blood pressure management
 Cardiac monitoring
 Control of fever
 Blood sugar regulation
 Fluid and electrolytes

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Respiratory monitoring
 Adequate oxygenation is important to
preserve the penumbra
 Most common causes of hypoxemia in
stroke
Previous pulmonary disease
Airway obstruction
Acute aspiration
Hypoventilation due to large hemispheric
infarct or bleed , brainstem involvement,
seizure, heart failure and pulmonary
embolism

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Respiratory monitoring
 no data favor O2 administration to all stroke
patients
 O2 administration is required in case of
hypoxemia ( O2 sat <92%)
 Consider intubation in case of
○ Severe pre existing and /or acute pulmonary disease
○ Acute aspiration
○ Impaired level of consciousness with risk of aspiration
○ Loss of caudal brainstem reflexes

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Blood Pressure Management
Why treat?
 Worsens cerebral blood flow
 Promotes hemorrhagic transformation
and ICH after t-PA
Why withhold treatment?
 Precipitous decline may worsen
ischemia

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Guidelines in BP Management in
Acute Ischemic Stroke (first 5 days)
 Avoid precipitous drop in BP; not > 20% of baseline MAP
 Do not use rapid acting sublingual agents e.g. Nifedipine
 Use easily titratable IV anti-HPN medications e.g.
Nicardipine, Esmolol
 Treat if with any of the ff: SBP > 220 or DBP > 120 or MAP
> 130mm Hg

Stroke Society of the Phil. . 2002

WHO-ISH , 1999

AHA Scientific Statement, 2003

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Anti hypertensive Medications
 Indicated for:
aortic dissection
acute myocardial infarction
heart failure
acute renal failure
hypertensive encephalopathy
thrombolytic therapy

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Cardiac monitoring
 Cardiac enzymes may be elevated after
stroke
 15% to 40% of stroke patients may
experience
arrhythmias (AF)
congestive heart failure
AMI
sudden death

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Cardiac monitoring
 At hospital entry: ECG and clinical chemistry to
check for concomitant MI
 Continuous cardiac monitoring in the first 48 hours
of stroke onset
 Abnormal baseline ECG
 previous known cardiomyopathies
 History of arrythmias
 Heart failure
 Unstable blood pressure
 infarct in the insular cortex

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Body temperature
 Body temperature increase in 50% of
patients

Why treat?
Fever increase infarct size
High body temperature increase stroke
progression and bad outcome
 Why withhold treatment?
Inc. temperature is part of the acute phase
response

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 Body Temperature

 Treatment is advisable if temperature

>37.5 C
 85% of fever in stroke are due to
infectious disease
 Search for possible infection is
necessary to start appropriate treatment

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Fluid and Electrolyte
 All acute stroke patients need hydration
D5 containing and hypotonic solutions (NaCl 0.45%)
are contraindicated : risk of brain edema
Glucose solutions are contraindicated: detrimental
effect of hyperglycemia
PNSS at 80cc/hour
 Hypokalemia may appear during insulin infusion
 Hyponatremia may be consequent to
○ Inadequate antidiuretic hormone secretion syndrome
○ Cerebral salt wasting syndrome

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Hyperglycemia in Stroke
 Accounts for 25 to 50% of patients
 Associated with worse outcome
increases cerebral edema
hemorrhagic transformation of ischemic strokes
increases mortality with BS > 130mg%
 EUSI and AHA Recommendations:
- Treat hypoglycemia
- Give Insulin for Blood Glucose > 300 mg
%

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 Effective Acute Stroke Treatment
based on Evidence

Treatment NNT
Aspirin w/in 48 hrs. 81.1
Stroke Unit 19.3
rTPA
overall 18.3
0-3 hours 9.1
3-6 hours 33.6

Bussiere M, Wiebe S, et al
Can. J. Neurol. Sci. 2005;32:440-49

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IV tPA - Acute Ischemic Stroke Inclusion Criteria*

 Age 18 through 79 years

 Clinical diagnosis of ischemic stroke causing a
measurable neurologic deficit.
 Reliably timed onset of symptoms of ischemic
stroke within 3 hours of the time to initiation of
treatment with intravenous tPA
*Adapted from guidelines published by the American
Heart Association and American Academy of Neurology.
Stroke 1996;27:1711-1718. Neurology 1996;47:835-839

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IV tPA - Acute Ischemic Stroke
Exclusion Criteria
 Symptoms rapidly improving
or very minor
 Hemorrhage on CT scan
 glucose < 50 or > 400, Hct <
25, or platelets < 100,000
 On anticoagulant therapy
 IV medications needed to
lower BP below 185/110
 Hx suggestive of
subarachnoid hemorrhage
 Presumed septic embolus
 Recent stroke, MI, trauma,
pregnancy, surgery
 Hx of any recent hemorrhage,
AVM, aneurysm, cancer,
bleeding diathesis, or other
serious or terminal illness
 Active or new seizures
 Any other condition that the
physician feels would pose a
significant hazard to the
patient if tPA therapy were
initiated.
Higher Hemorrhage Risk
 Age > 80 (unknown)
 Signs of a very severe stroke
 Early ischemia CT changes
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 NINDS tPA Stroke Trial

30 30
Hemorrhage
p < .05
20 20

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10
9 20
20 10

0 8
0
1
tPA Placebo tPA Placebo
NIHSS Excellent Total Death
Recovery (%) Rate (%)
NEJM, 1995
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rTPA RULE of “3”
 Should be given during the FIRST 3
HOURS
 30% will improve (complete recovery or
mild deficit)
 Improvement seen in 3 months

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Stroke: The Challenge

 Only 1-3% of all stroke victims receive

treatment with tPA in the US
 25% of Acute MI patients receive treatment
(lytics or PTCA) in the US
 Mean time to presentation
AMI: 3hrs
Acute Stroke: 4-10hrs

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Early secondary prevention
 Risk of recurrent stroke following stroke or TIA was
thought to be about 10%.

 Recent studies have suggested it is much higher

than this with a risk of:
first 7 days 8–12%
1 month1 1–15% 3 months
17–18.5%

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

Lovett JK, et al. Stroke 2003;34:e138-e140.
Coull AJ, et al. BMJ 2004;328:326–328
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EUSI and AHA:Heparin in Stroke
1. No recommendation for general use of heparin, LMWH
or heparinoids after ischemic stroke (Level I)
2. Full dose heparin for selected indications such as AF,
other cardiac sources with high risk of re-embolism,
arterial dissection, or high grade arterial stenosis (Level
IV)
3. DVT-prophylaxis

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Aspirin in Acute Stroke
 Recommendation: 160 to 325 mg/day within 24 to 48
hours
 Avoid in potential candidates for thrombolytic therapy
 Delay for at least 24 hours after the administration of
rtPA
 Do not administer prehospital (i.e. pre-CT)

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Antiplatelet & Anticoagulant therapy
 Aspirin reduces the risk of recurrent ischemic stroke by  18 %.
 Aspirin is as effective or more effective than anticoagulation in non-
cardioembolic stroke prevention.

 Warfarin is not recommended for non-cardioembolic strokes.

Antithrombotic Trialists’Collaboration.
BMJ 2002;324:71-86
.

Mohr JP, et al. NEJM 2001;345:1444–1451.

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Antiplatelet & Anticoagulant therapy
 CAPRIE trial
 Patients treated with clopidogrel had a 5.32% annual risk of
ischemic stroke, myocardial infarction or vascular death
whereas patients treated with aspirin had a 5.83% annual risk
of the same events.
CAPRIE Steering Committee. .
Lancet 1996;348:1329–1339

 ESPS2 study
 dipyridamole + ASA may be more effective than aspirin alone
 criticized for the low dose of aspirin used

Diener HC, et al.

J Neurol Sci 1996;143:1-13.

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Antiplatelet & Anticoagulant therapy

 Warfarin is the treatment of choice in patients with AF

  60% reduction of stroke in the primary prevention of stroke
in AF
.

Hart RG, et al.

Ann Intern Med 1999;131:492-501

 All patients with AF should be considered for warfarin

therapy unless there are contraindications.
 A similar benefit is found in the secondary prevention of
stroke in patients with AF.
.

EAFT (European Atrial Fibrillation

Trial) Study Group. Lancet 1993;342:1255–
1262

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Antihypertensive treatment
 Any agent is better than no agent!!
 If BP > 20/10 above goal, initiate Rx with 2
medications!!
 The choice of specific drugs and targets should be
individualized on the basis of reviewed data and
consideration of specific patient characteristic (ex, DM,
renal impairment, etc)

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Diabetes control
 More rigorous control of HTN and dyslipidemia should be
considered in patients with DM (BP targets of 130/80 mm
Hg)
 ACEIs and ARBs are recommended as first-choice
medications for patients with DM
 Glucose control is recommended to near normoglycemic
levels to reduce microvascular complications and
possibly macrovascular complications
 Hemoglobin A1c goal <7% 
JAMA. 2001;285:2486-97

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Statin therapy
 Statin therapy  risk of vascular events (including
myocardial infarction, cardiovascular death, and stroke) by 
25 %
Amarenco P, et al. Cerebrovasc Dis 2004;7(Suppl
1):81–88.

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Revascularization procedure
 Endarterectomy for patients with
symptomatic carotid artery stenosis
>70% effective in reducing incidence of
ipsilateral hemispheral stroke
 Carotid angioplasty and stenting

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Intracerebral hemorrhage
 Accounts for 10-
30% of all stroke
hospital admissions
 30 day Mortality
~35-52%; half in the
first 2 days
 Only 20% of ICH
patients functionally
independent at 6
months
Broderick J et al. Stroke 2007; 38: 2001-23

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 ICH score
Component Points
GCS
3-4 2
97 100
5-12 1 100
13-15 0 90
80 72
ICH vol

30D Mortality (%)

70
>30 1
60
<30 0 50
IVH 40
Yes 1 30 26
No 0 20 13
Age 10
0
0
>80 1 0 1 2 3 4 5
<80 0
ICH Score
Infratentorial origin
Yes 1
No 0

Hemphill JC, et al. Stroke 2001; 32: 891-7

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Management Goals
 Stop or slow initial bleeding during first
hours after onset
 Remove blood from parenchyma or
ventricles to eliminate mechanical and
chemical factors causing brain injury
 Management of complications of blood
in the brain (increased ICP, decreased
cerebral perfusion)
 General supportive management

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ICH related to Anticoagulation
 Occurs with a frequency of 0.3-0.6% per year
in patients on chronic warfarin tx
 OAT use increases risk for ICH, worsens the
severity of ICH and significantly increases
the likelihood of death when ICH occurs
 Hematoma expansion maybe be more
common and occur over a longer time frame
 Risk factors: age, history of hypertension,
intensity of anticoagulation, associated
conditions such as CAA, leukoaraiosis
Hart RG, et al. Stroke 2005; 36: 1588-93
Steiner T, et al. Stroke 2006; 37: 256-62

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EUSI Recommendations
 Normalization of INR (<1.5)
PCC
○ 10-30 (-50) U/kg
○ Measure INR after 15 min
○ If INR is still >1.5, consider redosing w/ reduced dose
FFP
○ 10ml/kg will reduce an INR of 4.2 to 2.4, an INR of 3.0
to 2.1, or an INR of 2.4 to 1.8
○ To reduce an INR of 4.2 to 1.4 would require 40ml/kg
Vitamine K
○ 1-2 x 5-10mg PO or IV

Cerebrovasc Dis 2006; 22: 294-316

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EUSI Recommendations
 Normalization of PTT after heparin
Protamine sulphate
○ 1.0-1.5ml protamine sulfate inactivates 1000
IU heparin of the total amount applied within
the last 4 hrs

 Prevention of DVT
Compression stockings
Low dose heparin/heparinoids

Cerebrovasc Dis 2006; 22: 294-316

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ICH related to Fibrinolysis
 Symptomatic ICH
3-9% of patients treated w/ IV tPA
6% of patients treated w/ IV + IA tPA
10.9% w/ IA prourokinase
30D mortality >60%
 No reliable data re: treatment
 Current recommended therapy:
Platelet infusion (6-8U) and cryoprecipate

Broderick J et al. Stroke 2007; 38: 2001-23

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Management Goals
 Stop or slow initial bleeding during first
hours after onset
 Remove blood from parenchyma or
ventricles to eliminate mechanical and
chemical factors causing brain injury
 Management of complications of blood
in the brain (increased ICP, decreased
cerebral perfusion)
 General supportive management

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Surgical Treatment of ICH
 Craniotomy
 Minimally invasive surgery
Endoscopic aspiration of hematoma
Stereotactic placement of flexible catheter
followed by administration of thrombolytic
agents

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STICH
 Early surgery vs initial conservative
therapy
 N = 1033
 Inclusion criteria
CT evidence of spontaneous supratentorial
ICH w/in 72 hours
Neurosurgeon uncertain of benefits of either
treatment
Min hematoma diameter 2 cm & GCS > 5

Mendelow AD, et al. Lancet 2005; 365: 387-397

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STICH

Mendelow AD, et al. Lancet 2005; 365: 387-397

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Mendelow AD, et al. Lancet 2005; 365: 387-397
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Surgical Treatment of ICH
 Cerebellar bleed
No prospective RCT
Patients w/ cerebellar hemorrhage >3cm
who are deteriorating neurologically or who
have brain stem compression and/or
hydrocephalus from ventricular obstruction
should have surgical removal of the
hemorrhage as soon as possible

Broderick J et al. Stroke 2007; 38: 2001-23

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Management Goals
 Stop or slow initial bleeding during first
hours after onset
 Remove blood from parenchyma or
ventricles to eliminate mechanical and
chemical factors causing brain injury
 Management of complications of blood
in the brain (increased ICP, decreased
cerebral perfusion)
 General supportive management

52
Treatment of ICP
 Head of bed elevation
 CSF drainage
 Analgesia and sedation
 Neuromuscular blockade
 Osmotic therapy
 Hyperventilation
 Barbiturate coma

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Hyperosmolar therapy
 Studies on mannitol, glycerol, and
steroids have been disappointing
 Therapy should be directed at patients
with deterioration secondary to mass
effect or hydrocephalus

54
Management Goals
 Stop or slow initial bleeding during first
hours after onset
 Remove blood from parenchyma or
ventricles to eliminate mechanical and
chemical factors causing brain injury
 Management of complications of blood
in the brain (increased ICP, decreased
cerebral perfusion)
 General supportive management

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Brain supportive therapy
 Blood pressure management
 Ventilatory support
 Glucose control
 Fever control
 Management of seizures
 Nutritional supplement
 Prophylaxis for DVT

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Guidelines for BP management
 SBP >200 or MAP >150
Aggressive BP lowering w/ IV anti HPN, w/
BP monitoring q5 min
 SBP >180 or MAP >130
w/  ICP – monitor ICP and reduce BP w/
intermittent or IV meds to keep CPP >60-80
w/ normal ICP – reduce BP to MAP=110 or
BP 160/90 using intermittent or IV meds;
monitor patient q15 min

Broderick J et al. Stroke 2007; 38: 2001-23

57
IV drugs used in ICH
 Labetalol  Enalaprilat
 Esmolol  Hydralazine
 Urapidil  Fenoldam
 Nitroprusside  Furosemide
 Nicardipine

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Brain supportive therapy
 Antiepileptic drugs
Seizures after ICH
○ occurred at onset in 4% of patients
○ 30 day risk of seizure post ICH - 8%
cEEG abnormal in 28% in 1st 72 hrs
○ Associated w/ higher NIHSS scores and midline shift
○ trend towards poor outcome
Lobar hematomas associated with early seizures
No RCT re: prophylactic AED use

Passero et al. Epilepsia 2002; 43 (10): 1175-80

Vespa et al. Neurology 2003; 60: 1441-6
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60
EVIDENCE-BASED
MANAGEMENT OF
STROKE
Maria Leticia Araullo, MD FPNA
Neurologist – Psychiatrist

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