Management Acute Stroke

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Management AcuteIschemic Stroke

Prof Dr. dr. Rusdi Lamsudin MMedScNeurologist

Department of Neurology

YARSIS HOSPITAL

Department of Neurology

Faculty of Medicine

Indonesian Islamic University



Prof.Dr.dr. H. Rusdi Lamsudin, M.Med.Sc

Neurologist

Medical Doctor, Faculty of Medicine, UGM, 1971

Neurologist, Unair-UGM, 1978

Master of Medical Sciences, New Castle Univ, Australia, 1986

Head of Executive Board Muhammadiyah Hospital, Yogyakarta, 1993-1999

Vice Dean, Faculty of Medicine Muhammadiyah Yogyaakarta University,1993-1999

PhD, UGM, 1996

Short-course, Unit Stroke & Neuro-Intensive, Insburck, Austria,1997

Head of Stroke Unit, Sardjito Hospital, Yogyakarta, 2001-2005

Head of Neurology Department Faculty of Medicine, UGM, 2001-2005Dean of Faculty Medicine, Indonesia Islamic University, Yogyakarta, 2001-2006, 2006-2010

Head of Neurology Department YARSIS Hospital, Surakarta

President IIMA, 2006-2012



References

1. Guidelines for stroke management; ESO Guideline2009

2. Clinical Guidelines for acute stroke; StrokeManagement Suppl. National Stroke Foundation,

Australia 2008

3. Clinical Guidelines; the diagnosis and acute strokemanagement of stroke and transient ischemic attack.NICE 2008

4. Guidelines for early management adult with ischemicstroke. AHA/ASA 2007

5. Canadian Best Practice. Recommendation for strokecare. Recommendation 4, 2006; acute strokemanagement



Outlines

1. Education, Referral and Emergency

room

2. Stroke Unit

3. Imaging and Diagnostics

4. Prevention

5. General Treatment

6. Acute Treatment7. Management of Complications

8. Rehabilitation



Stroke as an Emergency

Background

– Stroke is the most important cause of morbidity and long term

disability in the world1

– Demographic changes are likely to result in an increase in both

incidence and prevalence

– Stroke is also the second most common cause of dementia, the

most frequent cause of epilepsy in the elderly, and a frequent

cause of depression2,3

1: Lopez AD et al. Lancet (2006) 367:1747-1757

2: Rothwell PM et al. Lancet (2005) 366:1773-1783

3: O'Brien JT et al. Lancet Neurol (2003) 2:89-98




Background

– Stroke is a medical and occasionally a surgical

emergency

– The majority of ischaemic stroke patients do notreach the hospital quickly enough

– The delay between stroke onset and hospital

admission is;

reduced if the Emergency Medical Systems (EMS) are used

increased if doctors outside the hospital are consulted first




Emergency care in acute stroke depends on a four-step

chain:

– Rapid recognition of, and reaction to, stroke signs and symptoms

– Immediate EMS contact and priority EMS dispatch

– Priority transport with notification of the receiving hospital

– Immediate emergency room triage, clinical, laboratory and

imaging evaluation, accurate diagnosis, and administration of

appropriate treatments at the receiving hospital




Delays during acute stroke management have been

identified at three different levels1

– at the population level, due to failure to recognize the symptoms

of stroke and contact emergency services

– at the level of the emergency services and emergency

physicians, due to a failure to prioritize transport of stroke

patients

– at the hospital level, due to delays in neuroimaging and

inefficient in-hospital care

1:Kwan J et al. Age Ageing (2004) 33:116-121



Education

Recommendations

Educational programmes to increase awareness of

stroke at the population level are recommended

(Class II, Level B)

Educational programmes to increase stroke awareness

among professionals (paramedics, emergency

physicians) are recommended (Class II, Level B)



Referral

Recommendations (1/2)

Immediate EMS contact and priority EMS dispatch are

recommended (Class II, Level B)

Priority transport with advance notification of thereceiving hospital is recommended (Class III, Level B)

Suspected stroke victims should be transported without

delay to the nearest medical centre with a stroke unit

that can provide ultra-early treatment (Class III, Level B)

Patients with suspected TIA should be referred without

delay to a TIA clinic or a stroke unit (Class III, Level B)



Referral


Dispatchers and ambulance personnel should be trained to

recognise stroke using simple instruments such as the Face-Arm-

Speech-Test (Class IV, GCP)

Immediate emergency room triage, clinical, laboratory and imaging

evaluation, accurate diagnosis, therapeutic decision and

administration of appropriate treatments are recommended (Class

III, Level B)

In remote or rural areas helicopter transfer and telemedicine shouldbe considered to improve access to treatment (Class III, Level C)



Emergency Management

The time window for treatment ofpatients with acute stroke is narrow – Acute emergency management of stroke

requires parallel processes operating atdifferent levels of patient management

– Acute assessment of neurological and vital

functions parallels the treatment of acutelylife-threatening conditions

Time is the most important factor




The initial examination should include – Observation of breathing and pulmonary function and

concomitant heart disease

– Assessment of blood pressure and heart rate

– Determination of arterial oxygen saturation

– Blood samples for clinical chemistry, coagulation andhaematology studies

– Observation of early signs of dysphagia

– Targeted neurological examination

– Careful medical history focussing on risk factors forarteriosclerosis and cardiac disease



Ancillary Diagnostic Tests

In all patients

– Brain Imaging: CT or MRI

– ECG

– Laboratory Tests

Complete blood count and platelet count,

prothrombin time or INR, PTT

Serum electrolytes, blood glucoseCRP or sedimentation rate

Hepatic and renal chemical analysis



Ancillary Diagnostic Tests

In selected patients

– Duplex / Doppler ultrasound

– MRA or CTA

– Diffusion and perfusion MR or perfusion CT – Echocardiography, Chest X-ray

– Pulse oximetry and arterial blood gas analysis

– Lumbar puncture – EEG

– Toxicology screen




Recommendations

Organization of pre-hospital and in-hospital

pathways and systems for acute stroke patients

is recommended (Class III, Level C)

All patients should receive brain imaging, ECG,

and laboratory tests. Additional diagnostic

examinations are necessary in selected patients

(Class IV, GCP)



Outlines


room

2. Stroke Unit


4. Prevention



8. Rehabilitation



Stroke Unit

A stroke unit

– Is a dedicated and geographically defined part of a

hospital that takes care of stroke patients

– Has specialised staff with coordinatedmultidisciplinary expert approach to treatment and

care

– Comprises core disciplines: medical, nursing,

physiotherapy, occupational therapy, speech and

language therapy, social work 1

1:Langhorne P et al. Age Ageing (2002) 31:365-371



Stroke Unit

Typical components of stroke units include

– Assessment

Medical assessment and diagnosis, early assessment of

nursing and therapy needs – Early management policies

Early mobilisation, prevention of complications, treatment of

hypoxia, hyperglycaemia, pyrexia and dehydration

– Ongoing rehabilitation policiesCoordinated multidisciplinary team care

Early assessments of needs after discharge



Stroke Unit

Treatment at a stroke unit compared to

treatment in a general ward1

– reduces mortality (absolute risk reduction of 3%)

– reduces dependency (5%)

– reduces need for institutional care (2%)

All types of patients, irrespective of gender, age,

stroke subtype and stroke severity, appear tobenefit from treatment in stroke units1

1:Stroke Unit Trialists' Collaboration Cochrane Rev (2007)



Stroke Services and Stroke Units

Recommendations

All stroke patients should be treated in a stroke unit

(Class I, Level A)

Healthcare systems must ensure that acute strokepatients can access high technology medical and

surgical stroke care when required (Class III, Level B)

The development of clinical networks, including

telemedicine, is recommended to expand the access to

high technology specialist stroke care (Class II, Level B)



Outlines


room

2. Stroke Unit


4. Prevention



8. Rehabilitation





Emergency Diagnostic Tests

Cranial Computed Tomography (CT)

– Immediate plain CT scanning distinguishes reliably

between haemorrhagic and ischaemic stroke

– Detects signs of ischaemia as early as 2 h after strokeonset1

– Helps to identify other neurological diseases (e.g.

neoplasms)

– Most cost-effective strategy for imaging acute strokepatients2

1: von Kummer R et al. Radiology (2001) 219:95-100

2: Wardlaw J et al. Stroke (2004) 35:2477-2483




Magnetic Resonance Imaging (MRI)

– Diffusion-weighted MRI (DWI) is more sensitive for detection of

early ischaemic changes than CT

– DWI can be negative in patients with definite stroke1

– Identifies ischaemic lesions in the posterior fossa reliably

– Detects even small intracerebral haemorrhages reliably on T2*

sequences

– MRI is particularly important in acute stroke patients with

unusual presentations

1: Ay H et al. Cerebrovasc Dis (2002) 14:177-186




Ultrasound studies

– Cerebrovascular ultrasound is fast and non-invasive

and can be administered using portable machines.

– It is therefore applicable to patients unable to co-operate with MRA or CTA1

– Combinations of ultrasound imaging techniques and

MRA can produce excellent results that are equal to

Digital subtraction angiography (DSA)2

1: Allendörfer J et al. Lancet Neurology (2005) 5:835-840

2: Nederkoorn P et al. Stroke (2003) 34:1324-1332




Electrocardiogram (ECG)

– Cardiac abnormalities are common in acute stroke patients1

– Arrhythmias may induce stroke, stroke may cause arrhythmias

– Holter monitoring is superior to routine ECG for the detection of

atrial fibrillation (AF)2

– It is unclear whether continuous ECG recording at the bedside is

equivalent to Holter monitoring for the detection of AF

1: Christensen H et al. Neurol Sci (2005) 234:99 –103

2: Gunalp M et al. Adv Ther (2006) 23:854-60




Echocardiography (TTE / TOE)

– Echocardiography can detect many potential causes of stroke1

– It is particularly required in patients with history of cardiac

disease, ECG pathologies, suspected source of embolism,

suspected aortic disease, suspected paradoxical embolism

– Transoesophageal echocardiography (TOE) might be superior to

transthoracic echocardiography (TTE) for the detection of

potential cardiac sources of embolism2

1: Lerakis S et al. Am J Med Sci (2005) 329:310-6

2: de Bruijn SF et al. Stroke (2006) 37:2531-4




Laboratory tests

– Haematology (RBC, WBC, platelet count)

– Basic clotting parameters

– Electrolytes

– Renal and hepatic chemistry

– Blood Glucose – CRP, sedimentation rate



Diagnostic Imaging

Recommendations

In patients with suspected TIA or stroke, urgent cranial CT (Class I),

or alternatively MRI (Class II), is recommended (Level A)

If MRI is used, the inclusion of diffusion weighted imaging (DWI) and

T2*-weighted gradient echo sequences is recommended (Class II,Level A)

In patients with TIA, minor stroke, or early spontaneous recovery

immediate diagnostic work-up, including urgent vascular imaging

(ultrasound, CT-angiography, or MR angiography) is recommended

(Class I, Level A)



Other Diagnostics


In patients with acute stroke and TIA, early evaluation of

physiological parameters, routine blood tests, and

electrocardiography (ECG) is recommended (Class I,Level A)

All acute stroke and TIA patients should have a 12-

channel ECG. Continuous ECG recording is

recommended for ischaemic stroke and TIA patients(Class I, Level A)



Other Diagnostics


For stroke and TIA patients seen after the acute phase,

24-hour Holter ECG monitoring should be performed

when arrhythmias are suspected and no other causes ofstroke are found (Class I, Level A)

For all stroke and TIA patients, a sequence of blood

tests is recommended

Echocardiography is recommended in selected patients(Class III, Level B)



Outlines


room

2. Stroke Unit


4. Prevention



8. Rehabilitation



Primary Prevention

Content

– Management of vascular risk factors

– Antithrombotic therapy

– Carotid surgery and angioplasty



Content

– Management of vascular risk factors

– Antithrombotic therapy

– Surgery and angioplasty

Secondary Prevention



Blood pressure control

Background

– Antihypertensive drugs reduce stroke

recurrence risk after stroke or TIA (RR 0.76;

95%CI 0.63-0.92)1

– Target BP level and reduction should be

individualized

– The reduction in stroke occurs regardless ofbaseline BP and type of stroke2

1: Rashid P et al.: Stroke (2003) 34:2741-8

2: PROGRESS group: Lancet (2001) 358:1033-41



Diabetes mellitus

Background

– In people with type 2 diabetes with previousstroke pioglitazone reduces fatal or nonfatal

stroke (HR 0.53; 95%CI 0.34-0.85;P=0.0085)1

– In addition there is a trend to reduce thecombined end point of death and major

vascular events (HR 0.78; 95%CI 0.60-1.02;P=0.067)1

1: Wilcox R et al.: Stroke (2007) 38:865-73





Vitamins

Background

– Beta carotene increased the risk (RR 1.10) of

cardiovascular death1

– Antioxidant supplements may increase mortality2

– Folate, B12, B6 vitamins given to lower homocysteine

levels may not reduce stroke recurrence and may

increase vascular events3

1: Vivekananthan D et al.: Lancet (2003) 361:2017-2023

2: Bjelakovic G et al.: JAMA (2007) 297:842-8573: Bonaa K et al.: N Engl J Med (2006) 354:1578-1588



Hormone Replacement Therapy

Background

– Oestrogen therapy is not effective in

secondary prevention after TIA or stroke and

may increase stroke severity1

1: Viscoli CM et al.: N Engl J Med (2001) 345:1243-9.



Sleep-disordered Breathing

Background

– Sleep-disordered breathing (SDB) is both a risk factor

and a consequence of stroke

– More than 50% of stroke patients have SDB, mostly inthe form of obstructive sleep apnoea (OSA).

– SDB is linked with poorer long-term outcome and

increased long-term stroke mortality1

– Continuous positive airway pressure is the treatmentof choice for OSA.

1: Bassetti CL: Semin Neurol (2005) 25:19-32



Risk Factor Management


Blood pressure should be checked regularly. Blood pressure

lowering is recommended after the acute phase, including in

patients with normal blood pressure (Class I, Level A)

Blood glucose should be checked regularly. Diabetes should bemanaged with lifestyle modification and individualized

pharmacological therapy (Class IV, GCP)

In patients with type 2 diabetes who do not need insulin, treatment

with pioglitazone is recommended after stroke (Class III, Level B)





Statin therapy is recommended (Class I, Level A)

Cigarette smoking should be stopped (Class III, Level C)

Heavy use of alcohol should be discouraged (Class IV, GCP)

Regular physical activity is recommended (Class IV, GCP)

A diet low in salt and saturated fat, high in fruit and vege-tables, and

rich in fibre is recommended (Class IV, GCP)





Subjects with an elevated body mass index are recommended to

take a weight-reducing diet (Class IV, Level C)

Antioxidant vitamins supplements are not recommended (Class I,

Level A)

Hormone replacement therapy is not recommended for the

secondary prevention of stroke (Class I, Level A)

Sleep-disordered breathing such as obstructive sleep apnoea is

recommended to be treated with continuous positive airwaypressure breathing (Class III, Level GCP)



Antithrombotic Therapy

Background: Aspirin

– 13% relative risk reduction for stroke after TIA or

stroke1

– Most widely studied dosages of aspirin are 50-150mg – The incidence of GI-disturbances with aspirin is dose

dependent

– No difference in effectiveness amongst low (<

160mg), medium (160 – 325mg) or high (500 -1500mg) dose aspirin1: Antithrombotic Trialists' Collaboration: BMJ (2002) 324:71-86




Background: Dipyridamole plus aspirin

– Relative risk reduction of vascular death, stroke or

myocardial infarction with the combination is

significantly greater (RR 0.82; 95%CI 0.71-0.91) than

with aspirin alone1,2

– ARR 1.0% per year (NNT 100)2

– Incidence of dipyridamole induced headache may be

reduced by increasing the dose gradually3

1: Diener HC et al.: J Neurol Sci (1996) 143:1-13

2: Halkes P et al.: Lancet (2006) 367:1665-1673

3: Chang YJ et al.: Cerebrovasc Dis (2006) 22:258-62




Background: Clopidogrel:

– Clopidogrel is slightly but significantly more

effective than medium-dose aspirin (RRR

8.7%, ARR 0,5%) in preventing vascularevents in patients with previous stroke, MI or

PAD1

1: CAPRIE Steering Committee: Lancet (1996) 348:1329-1339




Background: Clopidogrel plus aspirin

– Compared with clopidogrel the combination of aspirinand clopidogrel does not reduce the risk of ischaemicstroke, myocardial infarction, vascular death, or re-

hospitalisation1

– Compared with aspirin alone the combination doesnot reduce the risk of myocardial infarction, stroke, orcardiovascular death2

– Risk of life-threatening or major bleeding isincreased1,2

1: Diener H et al.: Lancet (2004) 364:331-337

2: Bhatt D et al.: N Engl J Med (2006) 354:1706-1717





Patients should receive antithrombotic therapy (Class I,

Level A)

Patients not requiring anticoagulation should receiveantiplatelet therapy (Class I, Level A). Where possible,

combined aspirin and dipyridamole, or clopidogrel alone,

should be given. Alternatively, aspirin alone, or triflusal

alone, may be used (Class I, Level A)





The combination of aspirin and clopidogrel is not

recommended in patients with recent ischaemic stroke,

except in patients with specific indications (e.g. unstableangina or non-Q-wave MI during the last 12 months, or

recent stenting); treatment should be given for up to 9

months after the event (Class I, Level A)

Patients who have a stroke on antiplatelet therapyshould be re-evaluated for pathophysiology and risk

factors (Class IV, GCP)



Anticoagulation

Background

– Oral antiocoagulation (target INR 2.0 – 3.0) reduces

the risk of recurrent stroke in patients with AF1

– Oral anticoagulation is well established for othercauses of embolism such as mechanical prosthetic

valve replacement, rheumatic valvular heart disease,

ventricular aneurysm and cardiomyopathy

– There is no indication for oral anticoagulation in

patients with non-cardiac cause of ischaemic stroke2

1: EAFT Study Group: Lancet (1993) 342:1255-1262

2: Mohr JP et al.: N Engl J Med (2001) 345:1444-1451



Anticoagulation

Specific issues – In patients with AF and stable coronary disease,

aspirin should not be added to oral anticoagulation1

– Some retrospective studies suggest that anticoagu-

lation may be beneficial in aortic atheroma2, fusiformbasilar artery aneurysms3, or arterial dissection4

– It is unclear if patients with patent foramen ovale(PFO) benefit from oral anticoagulation5

1: Flaker GC et al.: Am Heart J (2006) 152:967-73

2: Dressler FA et al.: J Am Coll Cardiol (1998) 31:134-83: Echiverri HC et al.: Stroke (1989) 20:1741-7

4: Engelter ST et al.: Stroke (2007) 38:2605-11

5: Mas JL et al.: N Engl J Med (2001) 345:1740-6





Anticoagulation should not be used after non-cardio-embolic

ischaemic stroke, except in some specific situations, such as aortic

atheromas, fusiform aneurysms of the basilar artery, cervical artery

dissection, or patent foramen ovale in the presence of proven deepvein thrombosis (DVT) or atrial septal aneurysm (Class IV, GCP)

If oral anticoagulation is contraindicated, combined low dose aspirin

and dipyridamole should be given (Class IV, GCP)





Oral anticoagulation (INR 2.0 –3.0) is recommended after ischaemic

stroke associated with AF (Class I, Level A). Oral anticoagulation is

not recommended in patients with co-morbid conditions such as

falls, poor compliance, uncontrolled epilepsy, or gastrointestinalbleeding (Class III, Level C). Increasing age alone is not a

contraindication to oral anticoagulation (Class I, Level A)

Patients with cardioembolic stroke unrelated to AF should receive

anticoagulants (INR 2.0-3.0) if the risk of recurrence is high (Class

III, Level C)



Carotid Endarterectomy (CEA)

Background1,2

– CEA reduces the risk by 48% of recurrent disablingstroke or death in patients with 70-99%NASCET

ipsilateral carotid artery stenosis

– If perioperative complications exceed 6%, the benefitof CEA will diminish; if it approaches 10%, the benefitwill vanish entirely

– There is also some risk reduction in male patientswith 50 - 69% stenosis of the ipsilateral carotid artery,

provided that the complication rate is below 3%

1: NASCET Collaborators: NEJM (1991) 325:445-453

2: Warlow C: Lancet (1991) 337:1235-1243





Carotid Endarterectomy

Specific issues

– The benefit from CEA is lower with lacunar stroke

– Patients with leuko-araiosis should be made aware of

the increased operative risk

– Occlusion of the contralateral ICA carries a higher

perioperative risk

– Continuation of aspirin is required until surgery, but

heparin may be used in very severe stenosis

– All grading of stenoses should be according to

NASCET-criteria



Surgery and Angioplasty


CEA is recommended for patients with 70 –99% stenosis

(NASCET criteria) (Class I, Level A). CEA should only

be performed in centres with a perioperativecomplication rate (all strokes and death) of less than 6%

(Class I, Level A)

CEA should be performed as soon as possible after the

last ischaemic event, ideally within 2 weeks (Class II,Level B)







Patients should remain on antiplatelet therapy both before and after

surgery (Class I, Level A)

Carotid percutaneous transluminal angioplasty and/or stenting

(CAS) is only recommended in selected patients (Class I, Level A).It should be restricted to the following subgroups of patients with

severe symptomatic carotid artery stenosis: those with contra-

indications to CEA, stenosis at a surgically inaccessible site, re-

stenosis after earlier CEA, and post-radiation stenosis (Class IV,

GCP)





Patients should receive a combination of

clopidogrel and aspirin immediately before and

for at least 1 months after stenting (Class IV,

GCP)

Endovascular treatment may be considered in

patients with symptomatic intracranial stenosis(Class IV, GPC)



Outlines


room

2. Stroke Unit3. Imaging and Diagnostics

4. Prevention



8. Rehabilitation



General Stroke Treatment

Content

– Monitoring

– Pulmonary and airway care

– Fluid balance

– Blood pressure

– Glucose metabolism

– Body temperature



Monitoring

Continuous monitoring

– Heart rate

– Breathing rate

– O2 saturationDiscontinuous monitoring

– Blood pressure

– Blood glucose

– Vigilance (GCS), pupils

– Neurological status (e.g. NIH stroke scale or

Scandinavian stroke scale)



Pulmonary function

Background

– Adequate oxygenation is important

– Improve blood oxygenation by administration of > 2 l

O2 – Risk for aspiration in patients with side positioning

– Hypoventilation may be caused by pathological

respiration pattern

– Risk of airway obstruction (vomiting, oropharyngealmuscular hypotonia): mechanical airway protection



Blood pressure

Background

– Elevated in most patients with acute stroke

– BP drops spontaneously during the first days

after stroke

– Blood flow in the critical penumbra passively

dependent on the mean arterial pressure

– There are no adequately sized randomised,controlled studies guiding BP management



Blood pressure

Specific issues

– Elevated BP (e.g. up to 200mmHg systolic or

110mmHg diastolic) may be tolerated in the acute

phase of ischaemic stroke without intervention

– BP may be lowered if this is required by cardiac

conditions

– Upper level of systolic BP in patients undergoing

thrombolytic therapy is 180mmHg

– Avoid and treat hypotension

– Avoid drastic reduction in BP



Glucose metabolism

Background

– High glucose levels in acute stroke may increase the

size of the infarction and reduce functional outcome

– Hypoglycemia can mimic acute ischaemic infarction – Routine use of glucose potassium insulin (GKI)

infusion regimes in patients with mild to moderate

hyperglycaemia did not improve outcome1

It is common practise to treat hyperglycemia with insulinwhen blood glucose exceeds 180mg/dl2 (10mmol/l)1: Gray CS et al.: Lancet Neurol (2007) 6:397-406

2: Langhorne P et al.: Age Ageing (2002) 31:365-71.



Body temperature

Background

– Fever is associated with poorer neurological outcome

after stroke

– Fever increases infarct size in experimental stroke – Many patients with acute stroke develop a febrile

infection

There are no adequately sized trials guiding temperature

management after strokeIt is common practice treat fever (and its cause) when

the temperature reaches 37.5°C





Intermittent monitoring of neurological status, pulse,

blood pressure, temperature and oxygen saturation is

recommended for 72 hours in patients with significantpersisting neurological deficits (Class IV, GCP)

Oxygen should be administered if sPO2 falls below 95%

(Class IV, GCP)

Regular monitoring of fluid balance and electrolytes isrecommended in patients with severe stroke or

swallowing problems (Class IV, GCP)





Normal saline (0.9%) is recommended for fluid replacement during

the first 24 hours after stroke (Class IV, GCP)

Routine blood pressure lowering is not recommended following

acute stroke (Class IV, GCP) Cautious blood pressure lowering is recommended in patients with

any of the following; extremely high blood pressures

(>220/120 mmHg) on repeated measurements, or severe cardiac

failure, aortic dissection, or hyper-tensive encephalopathy (Class IV,

GCP)





Abrupt blood pressure lowering should be avoided (Class II, Level

C)

Low blood pressure secondary to hypovolaemia or associated with

neurological deterioration in acute stroke should be treated withvolume expanders (Class IV GCP)

Monitoring serum glucose levels is recommended (Class IV, GCP)

Treatment of serum glucose levels >180mg/dl (>10mmol/l) with

insulin titration is recommended (Class IV, GCP)





Severe hypoglycaemia (<50 mg/dl [<2.8 mmol/l]) should

be treated with intravenous dextrose or infusion of 10 –

20% glucose (Class IV, GCP points) The presence of pyrexia (temperature >37.5°C) should

prompt a search for concurrent infection (Class IV, GCP)

Treatment of pyrexia (>37.5°C) with paracetamol and

fanning is recommended (Class III, Level C) Antibiotic prophylaxis is not recommended in

immunocompetent patients (Class II, Level B)



Outlines


room


4. Prevention



8. Rehabilitation



Specific Stroke Treatment

Content

– Thrombolytic therapy

– Early antithrombotic treatment

– Treatment of elevated intracranial pressure

– Prevention and management of complications



Thrombolytic Therapy (i.v. rtPA)

Background (NINDS1, ECASS I2 + II3, ATLANTIS4)

– Intravenous rtPA (0.9mg/kg, max 90mg) given within

3 hours of stroke onset, significantly improves

outcome in patients with acute ischaemic stroke

– Benefit from the use of i.v. rtPA beyond 3 hours is

smaller, but may be present up to at least 4.5 hours

– Several contraindications1: NINDS rt-PA Grp: New Engl J Med (1995) 333:1581-1587

2: Hacke W et al.: JAMA (1995) 274:1017-10253: Hacke W et al.: Lancet (1998) 352:1245-1251

4: Clark WM et al.: Jama (1999) 282:2019-26.



Specific issues

– A pooled analysis of the 6 i.v. rtPA trials confirms that

i.v. thrombolysis may work up to 4.5 hours1

– Caution is advised when considering i.v. rtPA in

persons with severe stroke (NIHSSS>25), or if the CT

demonstrates extended early infarcts signs

– Thrombolytic therapy must be given by an

experienced stroke physician after the imaging of the

brain is assessed by physicians experienced inreading this imaging study2

1: Hacke W et al.: Lancet (2004) 363:768-74

2: Wahlgren N et al.: Lancet (2007) 369:275-82



Thrombolytic Therapy (i.v. rtPA)

Specific issues – Factors associated with increased bleeding risk1

elevated serum glucose

history of diabetes

baseline symptom severity

advanced age

increased time to treatment

previous aspirin use

history of congestive heart failure

NINDS protocol violations

– None of these reversed the overall benefit of rtPA

1: Lansberg MG et al.: Stroke (2007) 38:2275-8

S ifi T



Specific Treatment


Intravenous rtPA (0.9 mg/kg BW, maximum 90 mg), with

10% of the dose given as a bolus followed by a 60-

minute infusion, is recommended within 3 hours of onset

of ischaemic stroke (Class I, Level A)

Intravenous rtPA may be of benefit also for acute

ischaemic stroke beyond 3 hours after onset (Class I,

Level B) but is not recommended for routine clinicalpractice. The use of multimodal imaging criteria may be

useful for patient selection (Class III, Level C)

S ifi T t t



Specific Treatment


Blood pressures of 185/110 mmHg or higher must be

lowered before thrombolysis (Class IV, GCP)

Intravenous rtPA may be used in patients with seizuresat stroke onset, if the neurological deficit is related to

acute cerebral ischaemia (Class IV, GCP)

Intravenous rtPA may also be administered in selected

patients over 80 years of age, although this is outsidethe current European labelling (Class III, Level C)

S ifi T t t



Specific Treatment


Intra-arterial treatment of acute MCA occlusion within a

6-hour time window is recommended as an option

(Class II, Level B)

Intra-arterial thrombolysis is recommended for acute

basilar occlusion in selected patients (Class III, Level B)

Intravenous thrombolysis for basilar occlusion is an

acceptable alternative even after 3 hours (Class III,Level B)

A ti l t l t th



Antiplatelet therapy

Background

– Aspirin was tested in large RCTs in acute (<48 h)

stroke1,2

– Significant reduction was seen in death and

dependency (NNT 70) and recurrence of stroke (NNT

140)

– A phase 3 trial for the glycoprotein-IIb-IIIa antagonist

abciximab was stopped prematurely because of an

increased rate of bleeding3

1: International-Stroke-Trial: Lancet (1997) 349:1569-1581

2: CAST-Collaborative-Group: Lancet (1997) 349:1641-1649

3: Adams HP, Jr. et al.: Stroke (2007)

A ti l ti



Anticoagulation

Unfractionated heparin – No formal trial available testing standard i.v. heparin

– IST showed no net benefit for s.c. heparin treatedpatients because of increased risk of ICH1

Low molecular weight heparin – No benefit on stroke outcome for low molecular

heparin (nadroparin, certoparin, tinzaparin, dalteparin)

Heparinoid (orgaran)

– TOAST trial neutral2 1: International-Stroke-Trial: Lancet (1997) 349:1569-1581

2: TOAST Investigators: JAMA (1998) 279:1265-72.

N t ti



Neuroprotection

No adequately sized trial has yet shownsignificant effect in predefined endpoints

for any neuroprotective substance

A meta-analysis has suggested a mildbenefit for citicoline1

1: Davalos A et al.: Stroke (2002) 33:2850-7

S ifi T t t



Specific Treatment


Aspirin (160 –325 mg loading dose) should be given within 48 hours

after ischaemic stroke (Class I, Level A)

If thrombolytic therapy is planned or given, aspirin or other

antithrombotic therapy should not be initiated within 24 hours (ClassIV, GCP)

The use of other antiplatelet agents (single or combined) is not

recommended in the setting of acute ischaemic stroke (Class III,

Level C)

The administration of glycoprotein-IIb-IIIa inhibitors is not

recommended (Class I, Level A)

S ifi T t t



Specific Treatment


Early administration of unfractionated heparin,

low molecular weight heparin or heparinoids is

not recommended for the treatment of patientswith ischaemic stroke (Class I, Level A)

Currently, there is no recommendation to treat

ischaemic stroke patients with neuroprotectivesubstances (Class I, Level A)

El t d I t i l P



Elevated Intracranial Pressure

Basic management – Head elevation up to 30°

– Pain relief and sedation

– Osmotic agents (glycerol, mannitol,hypertonic saline)

– Ventilatory support

– Barbiturates, hyperventilation, or THAM-buffer

– Achieve normothermia

Hypothermia may reduce mortality1

1: Steiner T et al.: Neurology (2001) 57(Suppl 2):S61-8.



El t d I t i l P





Surgical decompressive therapy within 48 hours

after symptom onset is recommended in patients

up to 60 years of age with evolving malignantMCA infarcts (Class I, Level A)

Osmotherapy can be used to treat elevated

intracranial pressure prior to surgery if this isconsidered (Class III, Level C)

El t d I t i l P





No recommendation can be given regarding

hypothermic therapy in patients with space-

occupying infarctions (Class IV, GCP)

Ventriculostomy or surgical decompression can

be considered for treatment of large cerebellar

infarctions that compress the brainstem (ClassIII, Level C)

O tlines



Outlines


room


4. Prevention



8. Rehabilitation

Management of Complications




Aspiration and pneumonia – Bacterial pneumonia is one of the most

important complications in stroke patients1

– Preventive strategies

Withhold oral feeding until demonstration of intactswallowing, preferable using a standardized test

Nasogastric (NG) or percutaneous enteral gastrostomy(PEG)

Frequent changes of the patient’s position in bed andpulmonary physical therapy

– Prophylactic administration of levofloxacin isnot superior to optimal care2

1: Weimar C et al.: Eur Neurol (2002) 48:133-40

2: Chamorro A et al.: Stroke (2005) 36:1495-500





Urinary tract infections – Most hospital-acquired urinary tract infections

are associated with the use of indwelling

catheters1

– Intermittent catheterization does not reduce

the risk of infection

– If urinary infection is diagnosed, appropriate

antibiotics should be chosen following basic

medical principles1: Gerberding JL: Ann Intern Med (2002) 137:665-70c





Deep vein thrombosis and pulmonaryembolism

– Risk might be reduced by good hydration andearly mobilization

– Low-dose LMWH reduces the incidence ofboth DVT (OR 0.34) and pulmonary embolism(OR 0.36), without a significantly increasedrisk of intracerebral (OR 1.39) or extracerebralhaemorrhage (OR 1.44)1,2

1: Diener HC et al.: Stroke (2006) 37:139-44

2: Sherman DG et al.: Lancet (2007) 369:1347-55





Pressure ulcer – Use of support surfaces, frequent repositioning,

optimizing nutritional status, and moisturizing sacral

skin are appropriate preventive strategies1

Seizures

– Prophylactic anticonvulsive treatment is not beneficial

Agitation

– Causal treatment must precede any type of sedation

or antipsychotic treatment1: Reddy M et al.: JAMA (2006) 296:974-84





Falls – Are common in every stage of stroke treatment

– Risk factors include cognitive impairment, depression,polypharmacy and sensory impairment1

– A multidisciplinary package focusing on personal andenvironmental factors might be preventive2

– Exercise, calcium supplements and bisphosphonatesimprove bone strength and decrease fracture rates instroke patients3,4

1: Aizen E et al.: Arch Gerontol Geriatr (2007) 44:1-12

2: Oliver D et al.: BMJ (2007) 334:82

3: Pang MY et al.: Clin Rehabil (2006) 20:97-111

4: Sato Y et al.: Cerebrovasc Dis (2005) 20:187-92





Dysphagia and feeding – Dysphagia occurs in up to 50% of patients with

unilateral hemiplegic stroke and is an independent

risk-factor for poor outcome1

– For patients with continuing dysphagia, options forenteral nutrition include NG or PEG feeding

– PEG does not provide better nutritional status or

improved clinical outcome, compared to NG2,3

1: Martino R et al.: Stroke (2005) 36:2756-632: Dennis MS et al.: Lancet (2005) 365:764-72

3: Callahan CM et al.: J Am Geriatr Soc (2000) 48:1048-54





Recommendations (1/4) Infections after stroke should be treated with appropriate antibiotics

(Class IV, GCP)

Prophylactic administration of antibiotics is not recommended, and

levofloxacin can be detrimental in acute stroke patients (Class II,Level B)

Early rehydration and graded compression stockings are

recommended to reduce the incidence of venous thromboembolism

(Class IV, GCP)

Early mobilization is recommended to prevent compli-cations such

as aspiration pneumonia, DVT and pressure ulcers (Class IV, GCP)





Recommendations (2/4) Low-dose s.c. heparin or low molecular weight heparins should be

considered for patients at high risk of DVT or pulmonary embolism

(Class I, Level A)

Administration of anticonvulsants is recommended to preventrecurrent seizures (Class I, Level A)

Prophylactic administration of anticonvulsants to patients with recent

stroke who have not had seizures is not recommended (Class IV,

GCP)

An assessment of falls risk is recommended for every stroke patient

(Class IV, GCP)








Oral dietary supplements are only recommended for

non-dysphagic stroke patients who are malnourished

(Class II, Level B)

Early commencement of nasogastric (NG) feeding

(within 48 hours) is recommended in stroke patients with

impaired swallowing (Class II, Level B)

Percutaneous enteral gastrostomy (PEG) feeding shouldnot be considered in stroke patients in the first 2 weeks

(Class II, Level B)

Rehabilitation



Rehabilitation

Early rehabilitation – More than 40 % of stroke patients need active

rehabilitation

– Active rehabilitation should start early,providing the patient is clinically stable

– Passive rehabilitation should be given if the

patient is unconscious or paralysed

– Rehabilitation should be continued as long as

perceptable recovery is taking place

Rehabilitation



Rehabilitation

Multidisciplinary stroke team for rehabilitation – Stroke physician

– Nurses experienced in stroke management

– Physiotherapist trained in stroke rehabilitation

– Occupational therapist skilled in stroke – Speech therapist familiar with speech problems in

stroke patients

– Neuropsychologist accustomed to stroke

rehabilitation – Social worker familiar with the problems of stroke

patients

Setting of Rehabilitation





Admission to a stroke unit is recommended for acute

stroke patients to receive coordinated multidisciplinary

rehabilitation (Class I, Level A)

Early discharge from stroke unit care is possible in

medically stable patients with mild or moderate

impairment providing that rehabilitation is delivered in the

community by a multidisciplinary team with strokeexpertise (Class I, Level A)






Rehabilitation should be continued after

discharge during the first year after stroke

(Class II, Level A)

Early initiation of rehabilitation is recommended

(Class III, Level C)

It is recommended that the duration and intensityof rehabilitation is increased (Class II, Level B)

Elements of Rehabilitation




Recommendations (1/3) Physiotherapy is recommended, but the optimal mode of delivery is

unclear (Class I, Level A)

Occupational therapy is recommended, but the optimal mode of

delivery is unclear (Class I, Level A) While assessment for communication deficits is recommended,

there are insufficient data to recommend specific treatments (Class

III, GCP)

Information should be provided to patient and carers but evidence

does not support use of a dedicated stroke liaison service for all

patients (Class II, Level B)





Recommendations (2/3) Rehabilitation must be considered for all stroke patients, but there is

limited evidence to guide appropriate treatment for the most

severely disabled (Class II, Level B)

While assessment for cognitive deficits appears desirable, there areinsufficient data to recommend specific treatments (Class I, Level

A)

Patients should be monitored for depression during hospital stay

and throughout follow up (Class IV, Level B)



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Management Acute Stroke

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