Management Acute Stroke

Management Acute Ischemic Stroke
Prof Dr. dr. Rusdi Lamsudin MMedSc Neurologist 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, 19931999 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, 2001-2005 Dean of Faculty Medicine, Indonesia Islamic University, Yogyakarta, 20012006, 2006-2010 Head of Neurology Department YARSIS Hospital, Surakarta President IIMA, 2006-2012
References
1. 2.
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5.
Guidelines for stroke management; ESO Guideline 2009 Clinical Guidelines for acute stroke; Stroke Management Suppl. National Stroke Foundation, Australia 2008 Clinical Guidelines; the diagnosis and acute stroke management of stroke and transient ischemic attack. NICE 2008 Guidelines for early management adult with ischemic stroke. AHA/ASA 2007 Canadian Best Practice. Recommendation for stroke care. Recommendation 4, 2006; acute stroke management
Outlines
1. Education, Referral and Emergency room 2. Stroke Unit 3. Imaging and Diagnostics 4. Prevention 5. General Treatment 6. Acute Treatment 7. 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 not reach 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 the receiving hospital is recommended (Class III, Level B) delay to the nearest medical centre with a stroke unit that can provide ultra-early treatment (Class III, Level B)
Suspected stroke victims should be transported without
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-ArmSpeech-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 should be considered to improve access to treatment (Class III, Level C)
Emergency Management
The time window for treatment of patients with acute stroke is narrow
Acute emergency management of stroke requires parallel processes operating at different levels of patient management Acute assessment of neurological and vital functions parallels the treatment of acutely life-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 and haematology studies Observation of early signs of dysphagia Targeted neurological examination Careful medical history focussing on risk factors for arteriosclerosis 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 glucose CRP 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
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 coordinated multidisciplinary 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 policies

Coordinated 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 to benefit 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 stroke
patients 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
Emergency Diagnostic Tests

Differentiate between different types of stroke
Assess the underlying cause of brain ischaemia
Assess prognosis
Provide a basis for physiological monitoring of the stroke patient Identify concurrent diseases or complications associated with stroke Rule out other brain diseases

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 stroke onset1 Helps to identify other neurological diseases (e.g. neoplasms) Most cost-effective strategy for imaging acute stroke patients2
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 cooperate 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: Allendrfer 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 of stroke 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
Primary Prevention
Content
Management of vascular risk factors Antithrombotic therapy Carotid surgery and angioplasty
Secondary Prevention
Content
Management of vascular risk factors Antithrombotic therapy Surgery and angioplasty
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 of baseline 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 previous stroke 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 the combined 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
High Cholesterol
Background
Atorvastatin (80mg) reduces stroke recurrence by 16%1 Simvastatin (40mg) reduces risk of vascular events in patients with prior stroke, and of stroke in patients with other vascular disease (RR 0.76)2 ARR for statin treatment is low (NNT 112-143 for 1 year)1 Statin withdrawal at the acute stage of stroke may be harmful3
1: Amarenco P et al.: N Engl J Med (2006) 355:549-559 2: Heart Protection Study: Lancet (2002) 360:7-22 3: Blanco M et al.: Neurology (2007) 69:904-10
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) 297:842-857 3: 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 in the 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 treatment of 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 be managed 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 airway pressure 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 aspirin
1: 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 vascular events 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 aspirin and clopidogrel does not reduce the risk of ischaemic stroke, myocardial infarction, vascular death, or rehospitalisation1 Compared with aspirin alone the combination does not reduce the risk of myocardial infarction, stroke, or cardiovascular death2 Risk of life-threatening or major bleeding is increased1,2
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 receive
antiplatelet 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. unstable angina 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 therapy
should 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 other causes 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 anticoagulation may be beneficial in aortic atheroma2, fusiform basilar 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) 31:134-8 3: 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 deep vein 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 2.03.0) 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 gastrointestinal bleeding (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 disabling stroke or death in patients with 70-99%NASCET ipsilateral carotid artery stenosis If perioperative complications exceed 6%, the benefit of CEA will diminish; if it approaches 10%, the benefit will vanish entirely There is also some risk reduction in male patients with 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
CEA should be performed as soon as possible (ideally within 2 weeks) after the last cerebrovascular event1,2 Elderly patients (>75 years) without organ failure or serious cardiac dysfunction benefit from CEA1 Women with symptomatic stenosis >70% should undergo CEA. Women with moderate stenosis should be treated medically2
1: Rothwell PM et al.: Lancet (2004) 363:915-924 2: Rothwell PM et al.: Stroke (2004) 35:2855-61
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 7099% stenosis
(NASCET criteria) (Class I, Level A). CEA should only be performed in centres with a perioperative complication 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)

CEA may be indicated for certain patients with stenosis
of 5069% (NASCET criteria); males with very recent hemispheric symptoms are most likely to benefit (Class III, Level C). CEA for stenosis of 5069% (NASCET criteria) should only be performed in centres with a perioperative complication rate (all stroke and death) of less than 3% (Class I, Level A)
CEA is not recommended for patients with stenosis of
less than 50% (NASCET criteria) (Class I, Level A)

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 contraindications to CEA, stenosis at a surgically inaccessible site, restenosis 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) patients with symptomatic intracranial stenosis (Class IV, GPC)
Endovascular treatment may be considered in
Outlines
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 saturation
Discontinuous 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, oropharyngeal muscular 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 insulin when 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 stroke It is common practice treat fever (and its cause) when the temperature reaches 37.5C

Intermittent monitoring of neurological status, pulse,
blood pressure, temperature and oxygen saturation is recommended for 72 hours in patients with significant persisting neurological deficits (Class IV, GCP)
Oxygen should be administered if sPO2 falls below 95%
(Class IV, GCP)

Regular monitoring of fluid balance and electrolytes is
recommended in patients with severe swallowing problems (Class IV, GCP)
stroke
or

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 with volume 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 >37.5C) should
prompt a search for concurrent infection (Class IV, GCP)

Treatment of pyrexia (>37.5C) with paracetamol and
fanning is recommended (Class III, Level C)

Antibiotic
prophylaxis is not recommended immunocompetent patients (Class II, Level B)
in
Outlines
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 contraindications
1: NINDS rt-PA Grp: New Engl J Med (1995) 333:1581-1587 2: Hacke W et al.: JAMA (1995) 274:1017-1025 3: 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 in reading 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
Specific Treatment
Intravenous rtPA (0.9 mg/kg BW, maximum 90 mg), with
10% of the dose given as a bolus followed by a 60minute 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 clinical practice. The use of multimodal imaging criteria may be useful for patient selection (Class III, Level C)
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 seizures
at 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 outside the current European labelling (Class III, Level C)
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)
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)
Anticoagulation
Unfractionated heparin
No formal trial available testing standard i.v. heparin IST showed no net benefit for s.c. heparin treated patients 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.
Neuroprotection
No adequately sized trial has yet shown significant effect in predefined endpoints for any neuroprotective substance A meta-analysis has suggested a mild benefit for citicoline1
1: Davalos A et al.: Stroke (2002) 33:2850-7
Specific Treatment
Aspirin (160325 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 (Class IV, 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 recommended (Class I, Level A)
inhibitors
is
not
Specific Treatment
Early administration of unfractionated heparin,
low molecular weight heparin or heparinoids is not recommended for the treatment of patients with ischaemic stroke (Class I, Level A)
Currently, there is no recommendation to treat
ischaemic stroke patients with neuroprotective substances (Class I, Level A)
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.

Malignant MCA/hemispheric infarction
Pooled analysis of three European RCTs (N=93)1,2:
Significantly decreases mortality after 30 days Significantly more patients with mRS <4 or mRS <3 in the decompressive surgery group after one year No increase of patients surviving with mRS=5
Surgery should be done within 48 hours1,2 Side of infarction did affect outcome1,2 Age >50 years is a predictor for poor outcome3
1: Vahedi K et al.: Lancet Neurol (2007) 6:215-22 2: Jttler E et al.: Stroke (2007) 38:2518-25 3: Gupta R et al.: Stroke (2004) 35:539-43

Surgical decompressive therapy within 48 hours
after symptom onset is recommended in patients up to 60 years of age with evolving malignant MCA infarcts (Class I, Level A)
Osmotherapy can be used to treat elevated
intracranial pressure prior to surgery if this is considered (Class III, Level C)

No recommendation can be given regarding
hypothermic therapy in patients with spaceoccupying infarctions (Class IV, GCP)

Ventriculostomy or surgical decompression can
be considered for treatment of large cerebellar infarctions that compress the brainstem (Class III, Level C)
Outlines
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 intact swallowing, preferable using a standardized test Nasogastric (NG) or percutaneous enteral gastrostomy (PEG) Frequent changes of the patients position in bed and pulmonary physical therapy
Prophylactic administration of levofloxacin is not 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 principles
1: Gerberding JL: Ann Intern Med (2002) 137:665-70c
Deep vein thrombosis and pulmonary embolism
Risk might be reduced by good hydration and early mobilization Low-dose LMWH reduces the incidence of both DVT (OR 0.34) and pulmonary embolism (OR 0.36), without a significantly increased risk of intracerebral (OR 1.39) or extracerebral haemorrhage (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 treatment
1: 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 and environmental factors might be preventive2 Exercise, calcium supplements and bisphosphonates improve bone strength and decrease fracture rates in stroke 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 for enteral 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) 36:2756-63 2: Dennis MS et al.: Lancet (2005) 365:764-72 3: Callahan CM et al.: J Am Geriatr Soc (2000) 48:1048-54
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)
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 prevent recurrent 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)
Calcium/vitamin-D supplements are recommended in stroke patients at risk of falls (Class II, Level B)
Bisphosphonates (alendronate, etidronate and risedronate) are recommended in women with previous fractures (Class II, Level B)
In stroke patients with urinary incontinence, specialist assessment and management is recommended (Class III, Level C)
Swallowing assessment is recommended but there are insufficient data to recommend a specific approach for treatment (Class III, 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)
not be considered in stroke patients in the first 2 weeks (Class II, Level B)
Percutaneous enteral gastrostomy (PEG) feeding should
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
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 stroke expertise (Class I, Level A)
Setting of Rehabilitation
Rehabilitation
should be continued after discharge during the first year after stroke (Class II, Level A) (Class III, Level C)
Early initiation of rehabilitation is recommended It is recommended that the duration and intensity
of rehabilitation is increased (Class II, Level B)
Elements of Rehabilitation
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)
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 are insufficient 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)
Drug therapy and non-drug interventions are recommended to improve mood (Class I, Level A)
Drug therapy should be considered to treat post stroke emotionalism (Class II, Level B)
Tricyclic or anticonvulsant therapy are recommended to treat poststroke neuropathic pain in selected patients (Class III, Level B)
Botulinum toxin should be considered to treat post-stroke spasticity, but functional benefits are uncertain (Class III, Level B)

Management Acute Stroke

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Management Acute Stroke

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Management Acute Ischemic Stroke

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

stroke at the population level are recommended (Class II, Level B)

recommended (Class II, Level B)

Suspected stroke victims should be transported without

Patients with suspected TIA should be referred without

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

Time is the most important factor

Ancillary Diagnostic Tests

Ancillary Diagnostic Tests

Early management policies

Ongoing rehabilitation policies

reduces need for institutional care (2%)

Stroke Services and Stroke Units

Emergency Diagnostic Tests

Emergency Diagnostic Tests

Emergency Diagnostic Tests

Detects even small intracerebral haemorrhages reliably on T2* sequences

Emergency Diagnostic Tests

Emergency Diagnostic Tests

Emergency Diagnostic Tests

Emergency Diagnostic Tests

CRP, sedimentation rate

(Class III, Level B)

Blood pressure control

Hormone Replacement Therapy

Risk Factor Management

Risk Factor Management

Statin therapy is recommended (Class I, Level A)

Risk Factor Management

Carotid Endarterectomy (CEA)

Surgery and Angioplasty

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

Surgery and Angioplasty

less than 50% (NASCET criteria) (Class I, Level A)

Surgery and Angioplasty

Surgery and Angioplasty

Endovascular treatment may be considered in

General Stroke Treatment

General Stroke Treatment

(Class IV, GCP)

recommended in patients with severe swallowing problems (Class IV, GCP)

General Stroke Treatment

General Stroke Treatment

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

General Stroke Treatment

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

fanning is recommended (Class III, Level C)

prophylaxis is not recommended immunocompetent patients (Class II, Level B)

Specific Stroke Treatment

Thrombolytic Therapy (i.v. rtPA)

Thrombolytic Therapy (i.v. rtPA)

None of these reversed the overall benefit of rtPA

lowered before thrombolysis (Class IV, GCP)

6-hour time window is recommended as an option (Class II, Level B)

Low molecular weight heparin

The administration of glycoprotein-IIb-IIIa recommended (Class I, Level A)

ischaemic stroke patients with neuroprotective substances (Class I, Level A)

Elevated Intracranial Pressure

Elevated Intracranial Pressure

Elevated Intracranial Pressure

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

Elevated Intracranial Pressure

hypothermic therapy in patients with spaceoccupying infarctions (Class IV, GCP)